diff --git a/data/archive/pandemic-pact-grants-2024-11-03.csv b/data/archive/pandemic-pact-grants-2024-11-03.csv new file mode 100644 index 0000000..a46ed7f --- /dev/null +++ b/data/archive/pandemic-pact-grants-2024-11-03.csv @@ -0,0 +1,9863 @@ +GrantID,PubMedGrantId,GrantTitleEng,Abstract,PublicationYearOfAward,GrantEndYear,ResearchInstitutionName,GrantAmountConverted,StudySubject,Ethnicity,AgeGroups,Rurality,VulnerablePopulations,OccupationalGroups,StudyType,ClinicalTrial,Pathogen,InfluenzaA,InfluenzaH1,InfluenzaH2,InfluenzaH3,InfluenzaH5,InfluenzaH6,InfluenzaH7,InfluenzaH10,Disease,FundingOrgName,FunderCountry,FunderRegion,ResearchInstitutionRegion,ResearchLocationRegion,Tags,MPOXResearchPriority,MPOXResearchSubPriority,ResearchInstitutionCountry,ResearchLocationCountry,ResearchCat,ResearchSubcat,GrantStartYear +C00037,170359,COVID-19: Improving the Evidence to Treat an Emerging Infection Through Observational Studies and a Randomized Trial,"The clinical management of COVID-19 remains unclear. First, we do not know what the disease is yet; we are still learning a great deal about what it causes in humans. We do not know what treatments to give, what risk factors are present for severe disease, and how long people are sick. We are proposing a national observational study of hospitalized patients with confirmed COVID-19, with an embedded randomized clinical trial of an antiviral agent. The observational study will build on work that we have been doing for the past four years, with pre-established protocols and data collection infrastructure just for this purpose. The randomized clinical trial will be with global collaborators to make sure that Canadian patients inform the world, and vice versa, about how to best treat this new disease. Alongside this, we will conduct surveys of clinicians, researchers, and the public about how they understand this new outbreak, how they feel about participating in research during a major outbreak, and what should be done differently; all of which will inform our clinical studies. Finally, we have been asked by the WHO to conduct a formal guideline for the management of COVID-19, which we will perform as data begins to emerge from the clinical trials that are ongoing. All of these proposals, put together, create a suite of approaches to better understanding and managing a new infection. Our team is large and diverse, and has been prepared for this outbreak for a number of years, and are ready to help Canadians respond in an evidence-informed way",2020,-99,University of British Columbia,711273.7,Human Populations,Unspecified,Unspecified,,Unspecified,Unspecified,,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Clinical trial (unspecified trial phase), +C00038,"170357, 171495, 175580","Identification of biomarkers that predict severity of COVID-19 patients [Supplement added: Sex as a biological variable supplement, COVID-19 Variant Network]","The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are overwhelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.",2020,2022,University of Nova Scotia,874000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe | Western Pacific,Innovation,,,Canada,Canada | China | Viet Nam | Spain | Italy | Mozambique | Sudan | Ethiopia | Egypt | Morocco | Cote d'Ivoire,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C00040,"170353, 175493",Development of a rapid point-of-care diagnostic test for COVID-19 [Supplement added: COVID-19 Variant Supplement],"This research addresses the urgent need of rapid point-of-care diagnostics of COVID-19. The collaborative research is conducted by a multi-disciplinary team of virologists, chemists, infectious disease specialists, front-line practitioners, and public health researchers from the University of Alberta, Canadian Food Inspection Agency, and Wuhan Institute of Virology (China). The immediate priority focuses on developing two complementary techniques to be performed on-site and in resource-limited settings, in support of rapid diagnosis of COVID-19. The diagnostic innovation takes advantage of the most recent advances in chemistry, molecular biology, genome technology, and nanotechnology. Chemical reactions required for efficient amplification and sensitive detection of the viral RNA take place in a single tube at a moderate temperature, simplifying the operation procedures. The specific reaction products are visible to the naked eyes, thus eliminating the need for any elaborate equipment. The first test reads color changes, with red color indicating negative and blue color indicating positive. Readout for the second test is color band on paper strips, similar to those of pregnancy tests, with two red bands indicating positive whereas a single control band indicating negative. The mid-term priority focuses on validating and evaluating the new diagnostic tests for field applications in the epidemic center of COVID-19. Our team members in Wuhan who currently perform the standard diagnostic tests will lead this effort. Once validated and approved, the new diagnostic tools will be used to support screening and diagnosis of COVID-19 at the community level. The mid-term objective also includes adapting the point-of-care diagnostics at other collaborating sites, e.g., Karachi (Pakistan) and Nairobi (Kenya). A longer-term priority of this research includes refining the new diagnostic tools to enable monitoring of mutational changes of the virus as it continues to evolve.",2020,2022,University of Alberta,341980,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Eastern Mediterranean | Western Pacific,,,,Canada,China | Pakistan | Kenya,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00041,109434,"Rapid, Low-cost Diagnostics and Deployable Surge Capacity for COVID- 19","The outbreak of the coronavirus, first identified in Wuhan, China, highlights the importance of the capacity for a rapid and nimble response to infectious disease. As we have seen, the world in highly interconnected and outbreaks in one region quickly become global concerns. Diagnostics are a key tool in the fight against spread of the virus, allowing frontline responders to quickly triage patients. Over the past five years, our team has developed low-cost and de-centralized paper-based diagnostics that are simple to use and easy to distribute. During the Zika virus outbreak, we developed diagnostics within weeks and have since completed patient trials in Latin America showing performance equal to the gold standard CDC tests used in clinical labs (sensitivity equal qPCR test, 98.5% accuracy). These diagnostic, programmable by design, thus hold promise for managing future outbreaks. Seeking to contribute to the COVID-19 outbreak response, we have already begun the development of diagnostics for the virus and anticipate having validated tools within a month. Here we propose the following project to create a deployable diagnostic infrastructure for the virus: 1) A lab-in-a-box kit that can provide diagnostic surge capacity for COVID-19 (14,000 tests), 2) A package with the ""pop-up capacity"" to manufacture the diagnostics on-site for sustained response to the outbreak and 3) A point-of-need test for rapid screening of patients (e.g. cruise ships, airports). Such tools are important in Canada but are especially so in countries where health care systems do not have the resilience to handle a large outbreak. We have assembled a team of researchers from four countries with expertise in virology, diagnostics technologies and delivering impactful research outcomes. Our goal is a diagnostic platform capable of providing the capacity to respond to COVID-19 here in Canada or aboard, and the companion technologies, protocols and training to ensure effective deployment. Pillai",2020,-99,unknown,744839.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00043,170355,"Rapid Research Response to the 2019 Novel Coronavirus Outbreak: Development of Targeted Diagnostics, Therapeutics and Comparative Pathogenicity Assessment","In 2019, the world has seen the emergence of a virus that causes pneumonia in humans, which has a high probability of resulting in complications that include acute respiratory distress syndrome and death in an estimated 0.2% to 5% of cases. Coronavirus disease 2019 (COVID-19) is caused by a virus endemic in wild animals that has adapted itself to infect humans. The World Health Organization (WHO) has declared the 2019 outbreak of the novel coronavirus (2019-nCoV), which is now officially named SARS- CoV-2, a global health emergency. Currently, there is no effective antivirals against this virus. The virus is genetically similar to the 2003 Severe Acute Respiratory Syndrome-related coronavirus (SARS) and shares many disease features with influenza virus infections. Our team will combine its multidisciplinary expertise to develop genetically engineered antibodies that can be used as therapeutics to limit the spread of the virus, as well as help identify the virus in patient samples. We will also develop a rapid genetic test for SARS-CoV-2 and measure the speed of genetic evolution of this virus compared to other coronaviruses that cause disease in humans such as SARS that caused the 2003 outbreak and the middle east respiratory syndrome virus (MERS). Finally, we will mass produce the surface viral protein to enable the development of a prototype nasal-spray vaccine.",2020,-99,University of Ottawa,744838.38,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies, +C00045,170343,Development and Evaluation of SARS- CoV-2 RNA Polymerase Inhibitors,"Coronaviruses (CoV) can cause severe human respiratory diseases, which is documented by three major outbreaks over the past 17 years: SARS-CoV in 2003, MERS-CoV in 2011, and currently SARS-CoV-2. In response to the current COVID-19 outbreak caused by SARS-CoV-2, we oppose to develop novel tools to discover, develop and evaluate inhibitors of the viral polymerase. The polymerase is an enzyme that is essentially required for the propagation of SARS-CoV-2, which makes it an attractive target for therapeutic intervention strategies.",2020,-99,University of Alberta,502766.41,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies, +C00046,"170346, 175528",Rapid development of antiviral compounds to fight the COVID-19 outbreak [Added supplement: COVID-19 Variant Supplement],"The outbreak of a respiratory illness (COVID-19) in China at the end of December 2019 has been demonstrated to be caused by a new coronavirus. While health officials are using quarantine methods to try and prevent the spread of the infection, there are currently no treatments for the illness, which can be severe and even lead to death in 2% of cases. Here, we propose to build on our previous research with viruses of the same family, which include those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We have previously successfully engineered small proteins capable of blocking the activity of an enzyme of the virus that is crucial for its replication and for shutting down the human immune response. We plan on using a similar strategy to build blockers of the new virus. These will be extremely useful in better understanding the biology of the virus. Most importantly, we will use these blocking proteins to find chemical drug candidates that block the activity of the viral enzyme in infected cells, which can then be developed as therapeutics. Our method is rapid and cost efficient, and within the two years of this grant, we expect to have a number of lead candidate drugs. In order to achieve these goals, we have assembled a team of leading scientists with expertise in protein engineering of viral inhibitors (Sachdev Sidhu, University of Toronto), structural biology of viruses (Brian Mark, University of Manitoba), and development of chemical drugs (Roman Melnyk, SickKids Research Institute, Toronto). Our project also has the support of an internationally recognized leader in viral biology (Marjolein Kikkert, Leiden University, Netherlands) and a frontline clinician-scientist in infectious diseases (Samira Mubareka, Sunnybrook Health Centre, Toronto). Ultimately, this work will generate critical tools to better understand this new virus, and most importantly, will provide novel candidate drugs for direly needed therapies.",2020,2022,University of Toronto,712928.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Europe,,,,Canada,Canada | Netherlands,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C00047,170342,Preventing SARS-CoV- 2 infection by targeting human type II transmembrane serine protease activity,"The SARS-CoV-2 coronavirus causing COVID-19 has been declared a global emergency by the World Health Organization which has mobilized international scientists to collaborate in order to find therapies to counteract the virus's effects which can be devastating. The strategies need to be as vast as possible since we do not yet know if vaccines or other antiviral drugs will be efficacious. Our group had previously shown in the context of influenza infection that the human host has cell-surface proteases (called type II transmembrane serine proteases or TTSPs) that the virus requires in order to cleave a viral surface protein called hemagglutinin, itself essential for the virus to gain entry into the cell and further replicate using the host cell machinery. We had shown that small molecules inhibiting the activity of lung epithelial cell proteases were efficacious at significantly reducing influenza virulence demonstrating novel anti-viral properties of the compounds. The situation is similar with the SARS-CoV-2 virus but the protein found on the surface of the virus is different. This protein is called the spike glycoprotein (or S protein) and it requires cleavage by human host cell proteases of the TTSP family for its virulence. Our proposal will test protease inhibitors in models where cells are expressing the S protein and the most potent molecules will then be validated in lung organoids to verify their efficacy at reducing viral propagation. We have put together a team of molecular pharmacologists, chemists and virologist with access to containment level 3 facilities to rapidly assess the potential anti-viral properties of the compounds that we already have on hand. In addition, our team will be supported by Dr. Gary Whittaker, Cornell University, one of the world's experts in coronavirus biology. We believe that these conditions are very favorable for us to have a quick impact in the field and to deliver novel antiviral compounds for patients with COVID-19.",2020,-99,Université de Sherbrooke,637582.29,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | United States of America,"Therapeutics research, development and implementation",Pre-clinical studies, +C00048,170360,"Understanding, Forecasting and Communicating Risk During the COVID-19 Epidemic","A new infectious disease, COVID-19, has emerged worldwide. Canada has experienced few cases, but there is great concern about the possibility of a Canadian COVID-19 epidemic. Canada has a history of preparing for and managing disease outbreaks caused by new viruses (SARS, H1N1, preparing for Ebola). For many people inside and outside the public health community, an important part of preparation is having access to accurate, timely, reliable information about how the disease is spread, who is at risk, and who is not at risk. Public health professionals often want the answers to three basic questions about epidemics: ""when will it peak?""; ""when will it end?""; ""how big will it be?"". Our team of doctors, epidemiologists, public health professionals, and statisticians has experience responding to past outbreaks like SARS, H1N1 and Ebola. We are already actively involved in analysis and modeling that is helping public health agencies and the general public understand the COVID-19 epidemic, and ""see what's around the corner"". We have proposed a three-part project, which will use math and statistical modeling to: (i) forecast the near-term course of the epidemic; (ii) gain better understanding of the parts of the epidemic that are hidden from view, by analysing data that are public, but often messy or noisy; and (iii) use our information to build simulations that can help guide Canadian health agencies as they try to control or limit the spread of COVID-19 in Canada. Throughout this project, we will be creating infographics and tools that let Canadians inside and outside the scientific community gain a better understanding of how epidemics spread, who is truly at risk, and what it takes to make epidemics end. By providing timely information to Canadians, we will help reduce the fear, xenophobia and anxiety that are often part and parcel of emerging infectious diseases.",2020,-99,University of Toronto,247050.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Communication, +C00049,"170362, 175535",RIsk of environmental Surface and air Contamination in COVID19 (RISC- COV) [Added supplement: COVID-19 Variant Supplement],"This study has three goals. First, we will collect clinical and epidemiologic information about COVID-19 in Toronto and Peel region to share with ISARIC studies of the risk factors for, clinical features and outcomes of this infection in Canada and around the world. Second, we will collect data about how long patients with this infection shed virus, and whether this virus can be found on surfaces and in the air around patients with this infection, in order to help guide infection prevention practice. Third, we will systematically collect samples containing the virus, serum and cells of the immune system, in order to create a biobank that can be shared with investigators developing vaccines and treatment for this disease.",2020,2022,Sinai Health System,414229.52,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics | Disease pathogenesis,2020 +C00051,170363,Harnessing human mobility and surveillance data for disease forecasting to drive evidence-based public health policy during the COVID-19 epidemic,"COVID-19 emerged from Wuhan, China in late December 2019 and is currently spreading to international destinations, globally. At the time of writing, cases have been confirmed in 24 countries worldwide. Of major concern are early indications of human-to- human transmission outside of China in those without a travel history to China. During the two months of this epidemic, public health policy has adapted rapidly to emerging information about disease location, disease burden, and clinical features of COVID- 19. Public health screening and interventions will need to continuously evolve over the course of this epidemic to keep up with new foci of infection and potential new regions of COVID-19 exportation. We aim to harness validated tools to predict where COVID- 19 will spread in real time by using a novel, AI-driven web-based surveillance tool coupled with real-time human mobility data. This surveillance system identifies regions with real or suspected cases of COVID-19. We simultaneously harness global commercial air transportation data and geo-referenced mobile device data to reflect human mobility, also in real time. We have successfully validated these tools for COVID-19 forecasting during the course of this epidemic and published our results in peer-reviewed literature. We will first use the AIbased surveillance system to identify regions with confirmed and suspected COVID-19 cases. We will then model the spread of infection from these locations by harnessing human mobility data to identify and forecast new regions (at the city, regional, and national level) for virus importation. We will work closely with our partners in the World Health Organization, the Association of South East Asian Nations (ASEAN), and the International Air Transport Association (IATA) to use this data to help drive evidence-based public health policy in real time, with a focus on global projection strategies, and strategies for low and middle income countries in Southeast Asia.",2020,-99,University Health Network,502617.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | SSHRC,Canada,Americas,Americas,Americas | South-East Asia | Western Pacific,Digital Health,,,Canada,Canada | Singapore | Brunei Darussalam | Malaysia | Thailand | Philippines | Indonesia | Viet Nam | Lao People's Democratic Republic | Myanmar | Cambodia,Epidemiological studies,Disease transmission dynamics, +C00052,"170361, 171491",Rapid Response to Emerging Serious Pathogen Outbreaks using Next-gen Data: RESPOND [Added supplement: Sex as a biological variable Supplement],"A new virus has been identified from Wuhan City in China from the coronavirus family (SARS-CoV-2), which is now responsible for more than 71,000 cases of illness (COVID-19 disease) in over 29 countries. Although there have not yet been any deaths in Canada, public health agencies are on high alert, as there is a real possibility of a serious epidemic. The WHO has declared COVID- 19 a public health emergency of international concern. As of February 14th, five COVID-19 cases have been confirmed in British Columbia and based on travel patterns there is every reason to expect additional cases in BC. There are many unanswered questions regarding the virus, how it spreads and the disease that it causes. This information is needed for a data-driven response to this outbreak. We aim to use two types of next-generation data (next-gen genomics data and next-gen human data), along with a data integration tool called PLOVER 2.0, to answer these unknowns. The research team will 1)Carry out rapid genomic sequencing on patient samples to study the virus, how it spreads, how it evolves and predict which drugs will work 2)Develop knowledge of how the virus characteristics, along with a patient's previous health conditions, impact the severity of illness and how they recover from the illness 3)Develop a software tool (PLOVER 2.0) that will allow us to carry out this research and will also make the data viewable by key stakeholders such as Medical Health Officers. This work will not only generate critical knowledge about the SARS-CoV-2 virus but will also help develop a better understanding of health outcomes for infected patients. The knowledge generated and tools developed by this research can ensure an evidence-based and cohesive response to this public health emergency, here in Canada and internationally.",2020,2022,Anne University of British Columbia,777500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2020 +C00053,"170349, 171489",Animal models for SARS-CoV-2: vaccines and immune enhancement [Added supplement: Sex as a biological variable Supplement],"In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. In less than two months, there have been over 69,000 cases and over 1600 deaths. Quarantine measures have been imposed on entire cities in China in an attempt to control spread. Cases of SARS-CoV-2 have been identified in 28 other countries and there is concern that this could lead to global pandemic. Here we propose to identify what common lab and agricultural animals may be infected with SARS-CoV-2. This addresses two important questions. What animals can be infected and may pose a risk (or are at risk) and can these animals be used to models. Animal model allow us to understand how the virus causes disease, whether vaccines can be developed that protect from disease and how might the virus be transmitted. These are critical questions that need to be addressed when a new pathogen emerges. In addition, there is some concern that less than optimal vaccines or previous exposure to related pathogens could exaserbate disease - this is a somewhat unique phenomenom that was observed with SARS-CoV vaccines. We plan to investigate whether these animal models can be used to test for this, to ensure that vaccines are safe prior to testing in human clinical trials",2020,2022,University of Saskatchewan,794842.68,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Animal source and routes of transmission,2020 +C00054,"170347, 175525","Development of vaccine candidates and monoclonal antibodies to interrupt the spread of the novel coronavirus, COVID- 19 [Added supplement: COVID-19 Variant Supplement]","The novel coronavirus (Covid19) that emerged in Wuhan, China is a threat to global health. Infection causes respiratory disease that can progress to pneumonia, acute respiratory distress and even death. Often patients require hospitalization and intensive care, which increases the chance of viral spread within health care settings. Since it was first identified there have been over 69000 cases, and 1600 deaths, and the virus has spread to multiple countries. Currently, there are no vaccines or therapeutics, but these are urgently needed to bring the epidemic under control. Our proposal seeks to address these areas of need by a multifaceted approach. Specifically, the objectives of this proposal include: 1) Isolation of virus and generation of an in vitro reverse-genetics COVID-19 system 2) Identification of neutralizing antibodies 3) Development and evaluation of candidate vaccines Additionally, the project will generate data on the safety of candidate vaccines in humans through a phase I trial. This will help determine which vaccines can be advance for further study. This will be accomplished through synergistic research between the biotechnology companies Medicago and Inovio in conjunction with several academic research laboratories. Dr. Kobinger's group has an established track record of translational research, and has successfully brought a DNA-vaccine against MERS-CoV to phase I clinical trials 24 months after commencing the project and in less than 7 months for Zika virus. He has led multinational collaborations in the past, and has a history of promoting collaborative and transparent consortium-based research programs. This proposal will develop tools that can be shared with the world scientific community that will help further our understanding of viral pathogenesis, transmission as well as screen potential small-molecule inhibitors and antibodies. Collectively, the findings from this project have potential to contribute to global response against COVID19.",2020,2022,Université Laval,794633.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +C00055,"170348, 175527",Development of a nanoparticle-based vaccine candidate to the SARS-CoV-2 [Added supplement: COVID-19 Variant Supplement],"The recent outbreak of the coronavirus in the province of Wuhan in China is an international concern since there is a risk for spreading the infection outside the Chinese territory. The spreading of the virus is facilitated by its human to human transmission by aerosols. Several approaches must be taken to limit the spread of the virus, including quarantine, the decontamination of infected areas, early detection in patients, etc. It is also widely recognized that vaccination is from far the most efficient approach to control the spreading of the infection and protect the population. We propose first the development of a vaccine component-1 to the SARS- CoV-2 based on the use of an immune enhancer nanoparticle coupled to peptides derived from the virus nucleocapsid. This vaccine will trigger a protective immune response against the virus. The use of peptide antigens allows moving very fast in the development of the vaccine candidate. Besides the speed, this approach has the merit to induce a broad CTL immune response that should also trigger protection to any strains of the virus that are related to the Wuhan virus, like the SARS virus of 2002. Second, we will design and prepare a second vaccine component that will elicit the production of neutralizing antibodies to the SARS-CoV-2. Finally, both components will be combined in one vaccine formulation that will provide robust protection to the SARS-CoV-2 and also to related viruses, like the SRAS virus of 2002. The nanoparticles used to attach the vaccine antigens are very stable. The coupling to the nanoparticle will stabilize the antigens and generate a very stable vaccine formulation that can be stockpiled for a long period (years) without loss of integrity. This is an advantage because to insure preparedness to other epidemics with related viruses.",2020,2022,Université Laval,584910.2,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00060,170388,Towards Better Governance of Zoonotic Disease Risk: One Health Principles in the Coronavirus (COVID-19) Response,"The unfolding 2019-nCov outbreak presents an opportunity to establish a real-time monitoring infrastructure to study how One Heath principles are implemented in the global governance of infectious diseases (IDs). Through employing rapid environmental scan methodology and building on already existing research collaborations, we will be able to produce immediate results focused on the global coordination and response system that can feed into better global governance of 2019n-Cov, improving evidencebased decision-making and enhancing international collaborative efforts to mitigate the spread of 2019-nCov.",2020,-99,University of Ottawa,371901.16,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Health Systems Research,Health leadership and governance, +C00065,unknown,Developing integrated guidelines for health care workers in hospital and primary healthcare facilities in response to Covid-19 pandemic in Low- and MiddleIncome Countries (LMICs),"The proposal responds to the CIHR call regarding public health responses to the 2019 novel coronavirus (Covid-19) pandemic. We recognise the gap in LMICs where there is an under financed health system and low capacity of health care workers (HCWs) in hospitals, public and private primary care facilities and the community/ NGO to respond to the pandemic. The World Health Organization (WHO) has produced technical guidance, but the guidance documents are broad, they have to be updated with new developments, and translated into guidelines for HCWs, i.e., doctors, nurses and community health workers for hospitals, primary care and community in LMICs. Here we choose the Philippines and Sri Lanka because they both reported Covid-19 cases, and we can quickly mobilize resources. We aim to develop an integrated plan for HCWs to respond to the pandemic, as well as role-specific guidelines to manage Covid-19 suspects and cases regarding hospital patient flow, infection control, patient supervision and support in communities. We will learn from frontline experiences in China and update our understanding. We will work with policymakers, HCWs and NGOs in the Philippines and Sri Lanka to develop the guidelines and training modules. We will pilot test the tools for feasibility and acceptability among HCWs in the Philippines, adapt in Sri Lanka, and generate a generic version for LMICs to respond to Covid-19 and any future similar pandemic. Our integrated response strategy aims to update skills of HCWs, reduce patient overload at hospitals, avoid hospital transmission, reduce community transmission and public panic, provide patient support and reduce stigma. Our professional team consists of researchers from Canada, the Philippines, and Sri Lanka. The team has strong related experience and can quickly produce a draft guideline and materials within 2 months and finalize all work in 24 months.",2020,-99,University of Toronto,371069.92,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas | South-East Asia | Western Pacific,,,,Canada,Canada | Philippines | Sri Lanka,Health Systems Research | Research on Capacity Strengthening,Health service delivery | Health workforce | Cross-cutting, +C00067,170381,Destigmatizing Chinese Communities in the face of 2019-nCoV: Emergency Management Actions to Address Social Vulnerability in Toronto and Nairobi,"Chinese communities around the world are facing impacts to their personal wellbeing and livelihoods by way of discrimination and Sinophobia (anti-Chinese sentiment) due to COVID-19 disease (formally 2019-nCoV). By performing rapid response research, we can better understand social and policy countermeasures to mitigate the threats communities face from this and future Public Health Emergencies of International Concern (PHEIC). This project focuses on the research area of social and policy countermeasures. Specifically, cultural dimensions of the epidemic such as examining how individuals and communities understand and react to the disease along with tailoring a response to the unique circumstances of different populations will be the foci of this project. Our research team will: 1) examine how Chinese diaspora communities in large urban centres globally, namely in the Greater Toronto Area (GTA or Toronto herein), Canada and Nairobi, Kenya are understanding and reacting to the novel coronavirus by studying social impacts and coping strategies. 2) engage with vulnerable groups (children, women, elderly, etc.) within Chinese communities using participatory action research approaches to counter misinformation about COVID-19 and share emergency management and public health practices and resources relevant to the health crisis. 3) share findings with emergency management professionals in both countries and collaboratively develop a culturally-specific public education campaign to support efforts to destigmatize Chinese communities during the COVID-19 PHEIC in both Toronto and Nairobi. 4) use social media and knowledge sharing events to educate the broader community on the true impact of misinformation, disinformation, stigma and fear, with the hope that this will improve community cohesion during the outbreak phase, in recovery, and for future resilience.",2020,-99,York University,372419.56,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Kenya,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Social impacts, +C00070,170372,City Shutdown as a Response to COVID- 19: Understanding Human Experiences and Mental Health Consequences of the Quarantine in Wuhan,"Wuhan, where COVID-19 originated, is the capital of Hubei Province, with a population of over 11 million. The municipal government shut down the entire city since Jan 23, 2020, hoping to halt the COVID-19 outbreak. ""[B]elieved to be without precedent"" (New York Times), this largest quarantine in human history provides a natural case study to assess the impact of quarantine, as a public health response to COVID-19, on individuals and communities. We will conduct five waves of online survey, each four months apart, to follow a diverse sample of 8,000 adults who lived in Wuhan during the quarantine. The survey will evaluate respondents' mental health, challenges encountered, and community services received during and after the quarantine. We will use survey data to identify individual and community risk factors for mental health outcomes during and after the quarantine, thereby determining the course of post-quarantine recovery and pinpointing the populations that need public health services the most. We will also conduct in-depth interviews with 120 adults who lived in Wuhan during the quarantine to examine, in much greater detail, how people understood, reacted to, and coped with the quarantine, and what local barriers, challenges, and needs existed in combating the COVID-19 outbreak. Our interviews will target vulnerable groups who have special healthcare needs (pregnant women, people with chronic conditions, and the elderly living alone) and people who are primary caregivers (people who care for family members with COVID-19, healthcare workers, and parents of young children). Spanning the fields of public health, sociology, demography, and disaster studies, this research will illuminate the feasibility of quarantine as a public health response to COVID-19, inform community and mental health service planning for post-epidemic recovery, and ultimately help to mitigate potential negative impacts of quarantine and the COVID-19 outbreak on individuals and communities.",2020,-99,University of British Columbia,140811.84,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Urban Population/Setting,Pregnant women | Other,Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Western Pacific,Western Pacific,,,,Canada,China,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00071,170375,Digital Virtual Support of Cases and Contacts to Novel Coronavirus (COVID-19): Readiness and Knowledge Sharing for Global Outbreaks (WelTel PHM),"The global outbreak of COVID-19 is the latest example of a rapidly spreading infectious outbreak with global impact. Infected patients with mild symptoms and asymptomatic contacts need to be isolated, ideally without overwhelming health facilities. WelTel, an integrated virtual care and patient engagement solution, emerged as an innovation initially to support the global HIV pandemic through a Canadian-Kenyan partnership over a decade ago. Co-founded by the lead investigator and registered in British Columbia, WelTel has continued to integrate research into a richly featured virtual care platform that can be used on the frontlines of healthcare delivery. The study aims to: 1-Deploy and co-optimize WelTel to assist in home monitoring and support of COVID-19 cases and contacts; 2- Determine essential linkages and technical demands of the digital health ecosystem for data security purposes and integration into other electronic health records (EHR) & health information management systems (HIMS); 3-Evaluate communication and other metadata captured by the system for public health quality improvement to better understand and reduce barriers (such as stigma); 4-Use novel computing approaches such as natural language processing (NLP) and machine learning to harness artificial intelligence (AI) capabilities to model, predict, and provide insights into future precision public health approaches. Collaborators have necessary expert skills in quantitative and qualitative research methods for rigorous assessment, and come from the countries targeted for the research deployment (Canada, UK, US, Kenya, and Rwanda). A rapid digital landscape analysis will also be done as a part of this research. Virtual care may be an efficient, cost-effective way to provide the necessary public health monitoring and support for patients and contacts of COVID-19 and future emerging communicable pathogens, as well as can inform public health quality improvement and precision care.",2020,-99,University of British Columbia,372419.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe,Digital Health,,,Canada,Canada | United Kingdom | United States of America | Kenya | Rwanda,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C00072,170371,"kitatipithitamak mithwayawin: Indigenous-Led Countermeasures to Coronavirus (COVID- 19) and other Pandemics Then, Now, and Into the Future","The 2019 Novel Coronavirus (COVID-19) was first identified on December 31 2019 in Wuhan, China. As of February 18 2020, 73,439 COVID-19 cases have been confirmed in 29 countries around the world with an attributed 1,875 deaths. The World Health Organization recently declared COVID-19 as a global health emergency. Studies on H1N1 and other pandemics show that Indigenous communities in Canada suffered most from these diseases. Responses to H1N1 were often inadequate and at worst created more harm than good. Communities had poor access to medical experts and supplies. Indigenous organizations were mostly excluded from decision-making. And misinformation generated much fear that still persists today. Yet, many Indigenous communities and organizations also responded effectively and, with others, eventually found ways to reduce the impacts of H1N1. The outbreak of COVID-19 thus represents a critical moment. On one hand the same mistakes could be made, with similar impacts. On the other hand, there is an opportunity to do things differently in ways that are grounded in the priorities of Indigenous communities and organizations. The goal of this project is to evaluate the implications of past and existing responses to pandemics with respect to Indigenous communities across Canada and to address any gaps in understanding and support related to COVID-19 and future pandemics. This collaborative project will focus on the past by documenting experiences with other pandemics and explore changes in response over time. It will focus on the present by assessing current state of community emergency planning and risk communication. Finally, it will focus on the future by assessing community responses to different possible scenario and ideas for moving forward. We will share our outcomes with Indigenous communities and organizations across Canada, all levels of governments, and the general public so that the health interests of Indigenous people are best served now and into the future.",2020,-99,University of Manitoba,372419.56,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C00073,170376,Exploring the Psychosocial and Health Service Consequences of Coronavirus on Children and their Families: Lessons Learned for Pediatric Health Care Practice and Policy,"Outbreaks such as COVID-19 risk deleteriously affecting the quality of pediatric health care. For vulnerable children (e.g., those with COVID-19 or other respiratory conditions, those who are immunosuppressed, those with a terminal illness), person/family- centred care is essential to their health and well-being particularly in times of systemic challenge, which paradoxically is taxed during a pandemic outbreak. Studies have shown that outbreaks like COVID-19 strain practices such as imposing stringent infectious control procedures as well as widespread stigma and fear. These shifts risk negative impacts on tangible, relational (e.g., communication) and psychosocial aspects of care that can exacerbate patient anxiety and isolation both in and out of hospital. Procedural and other shifts in care may be needed to diminish negative impacts and conversely optimize patient care. Using qualitative data collection, this study will illuminate the perspectives of children, their families, and health care providers about how the COVID-19 outbreak has impacted public health and institutional health care delivery. Pediatric care processes and stakeholder experiences will be explored via ground theory methods. We will recruit pediatric patients with varying conditions, their parents and health care providers. Diversity in family ethno-cultural and socio-economic backgrounds will be sought. Interviews, focus groups and a Delphi consultation will be conducted, as will a comparison of these findings relative to similar data collected by members of this team during the 2003 Canadian SARS outbreak. Accordingly, potential advances in pandemic preparedness and care will be appraised. Recommendations for practice and policy will be offered.",2020,-99,University of Calgary,194676.37,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts, +C00074,170378,Spatial and social patterning of COVID- 19 prevention and transmission in Canada: Investigating the impacts of risk perception and preventive behaviour on individual activity space,"Emerging and re-emerging global infectious diseases are presenting unprecedented public health challenges, resulting in negative, long-lasting health, sociocultural and economic consequences for individuals and communities around the world. As a global city, Toronto is home to one of the most highly-travelled populations in the world. It has been a significant receiving geography of a number of global infectious diseases. The project aims to understand the relationships among health risk perception, community prevention behaviour and individual activity space during the on-going global COVID-19 outbreak. Disease transmission in an urban centre is directly influenced by individual activity space and the effectiveness of preventive measures taken in a community, which is largely shaped by perception of the disease and its risk. The project will (1) explore the perception of COVID-19 and its risks among groups with different immigration status, socio-economic-demographic characteristics within Toronto's Chinese community; (2) examine how risk perception shapes prevention behaviour and individual activity space; and (3) assess how activity space is influenced by risk perception, prevention practices, and other factors through spatial-quantitative, mapping and qualitative analysis. Data will be collected from a community survey on risk perception, prevention behaviour and daily mobility, and focus groups on coping strategies. The project will contribute to the global response to the COVID-19 outbreak by providing evidence- based findings on community prevention behaviour in a large urban hub. It will reveal local perspectives, citizen approaches and community practices as outbreak response effort, and enhance our understanding of the cultural dimensions of the epidemic. It will yield implications for public health response in setting policies under time constraints and uncertainty, allocating resources, identifying high-risk groups and setting vaccine priority.",2020,-99,Ryerson University,140811.84,Human Populations,Asian,Unspecified,Suburban Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication, +C00075,170379,Using Online News Media to Assess Community and Public Health Responses to COVID-19,"Canada has played a leading role in developing computer-based systems for scanning news on the internet to detect signals of infectious diseases. We will work with he Public Health Agency of Canada and the World Health Organization to develop artificial intelligence methods for analyzing news on the internet to understand how communities and public health agencies around the world are responding to the corona virus epidemic. These methods will help to understand the impact of the epidemic, identify effective strategies for controlling the epidemic, and contribute to improved global disease surveillance in the future.",2020,-99,McGill University,372419.56,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C00076,170365,"Chinese and non- Chinese Canadians Response to the 2019 Novel Coronavirus (COVID-19): Interrelations between Risk Perception, Discrimination, and Preventative Health Actions","The coronavirus (COVID-19) has triggered fear worldwide, and in Canada, some of this fear has been misplaced onto Chinese Canadians. The proposed research program is broadly concerned with Chinese Canadians' experiences of discrimination and stigmatization in the current context of the COVID-19 epidemic. Central to these experiences, we suggest, is non-Chinese Canadians' understanding of risk and the cultural dimensions of preventative health practices. The research program has three interrelated components that, together, will contribute to a comprehensive understanding of how Chinese and non-Chinese Canadians understand, experience, and react to the COVID-19, and have implications for developing strategies to combat stigma and fear associated with Chinese people and COVID-19. The first study involves a longitudinal study of Chinese Canadians' experiences of discrimination during the COVID-19 epidemic will help determine what kinds of support Chinese Canadians would like to receive now and in the near future. The second study focuses on non-Chinese Canadians' perceptions of risk associated with virus transmission. This study will test the idea that one way to allay fears aroused by viral outbreaks is to provide people with accurate numerical information about the mortality rate produced by the virus, and its main implication that reducing fear may decrease discrimination against Chinese Canadians. Risk perceptions also predict preventative behaviour. Thus, the third study focuses on wearing a face mask in public as a preventative health practice that is particularly enmeshed in cultural beliefs that differ across the two communities Together, these three interrelated components represent significant social countermeasure research to combat the intergroup threat driven by misinformation, stigma, and cultural misunderstanding associated with COVID-19.",2020,-99,University of Alberta,163551.78,Human Populations,Asian,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C00078,170368,"The dynamics of trust before, during, and after the COVID-19 outbreak","The proposed research aims to study the COVID-19 outbreak and its relationship with four different kinds of trust, namely- trust in government, trust in health agencies, social trust in general others, and outgroup trust (e.g. Chinese and non-Chinese). We will undertake this research with a view to meeting two objectives. First, we seek to investigate how the pre and in-crisis trust context has shaped the response to COVID-19 in China and Canada (Objective 1). Second, we seek to understand how the COVID-19 outbreak response and experience then shaped the post-crisis context of trust in in China and Canada (Objective 2). The inclusion of both countries is vital not only for the possible control that Canada provides to the Chinese case, but also because it will allow for a more global picture of the impacts that the crisis had on individuals who are ethnically Chinese living outside of China. We will make these contributions by analyzing existing trust data collected prior to the outbreak (pre-crisis); by adding questions about the outbreak to current surveys being conducted on trust in China by team members (in-crisis rapid response conducted immediately); by conducting a new rapidly developed online survey to be administered in China and Canada (in-crisis rapid response conducted immediately; repeated post crisis), and by conducting focus groups with citizens in Chinese and Canadian cities (in crisis Canada only rapid response; repeated post crisis both countries). We anticipate that our team, which brings together experts in trust and health from the center of the outbreak in China, including in Wuhan city, as well as leading scholars on trust and public health in Canada and Sweden, is ideally positioned to conduct this research. As a result of team members' ongoing and previous collaborations we are well-poised for the rapid engagement that is urgently needed in order to meet the global challenge posed by the COVID-19 outbreak.",2020,-99,York University,131282.37,Human Populations,Asian | Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Policies for public health, disease control & community resilience",Community engagement, +C00079,170370,The Paradox of Precaution: Examining Public Health COVID- 19 Outbreak Management Strategies,"In any outbreak, public health focuses on surveillance, containment, and providing recommendations for how the public can stay safe: wash hands, cover coughs, stay home when sick, and get vaccinated if one is available. While this is similar messaging to what is heard in cold/flu season, what separates these events apart is the inherent uncertainty involved during the emergence of a novel virus. However, when public health best practice (e.g. quarantining returning nationals from Wuhan) is attacked as putting people in ""medical jails"", or when the WHO implores governments for emergency resources to manage the outbreak by declaring the novel virus as ""public enemy number one"" akin to a ""global threat potentially worse than terrorism"", it creates a paradox around the concept of precaution. There is an urgent need to examine the cultural, social and political responses to the management of the current outbreak in real time. The objectives of this research are: 1) to evaluate how cautionary public health messages for the outbreak are presented by the news media; 2) to evaluate whether public health agencies are using social media and how well these tools, if used, increase public understanding of these outbreaks; 3) to assess how members of the general public, including special targeted groups, understand the outbreak, both the risks of disease and the risks of contraction; 4) to evaluate how effectively members of the public feel they can protect themselves given public health outbreak communication, and how they make sense of this relative to seasonal influenza risk messaging; and 5) to assess public response to a novel vaccine if one becomes available. We will meet these objectives through a content analysis of news media stories / social media, and interviews with public health communication leads (objs 1&2) and focus groups/surveys with members of the general public and targeted communities (e.g. Indigenous peoples, Asians) in select Canadian cities (objs 3-5).",2020,-99,University of Manitoba,372219.2,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00080,170367,Inoculating Against an Infodemic: Microlearning Interventions to Address CoV Misinformation,"The effort seeks to improve personal health and the health of populations by combating misinformation and developing online learning interventions that improve people's knowledge, skills, beliefs, and behaviours related to COVID-19. In particular, the effort uses a design thinking approach to (1) examine digital misinformation flows pertaining to the outbreak; (2) develop, test, and improve educational interventions to reduce the spread of online misinformation. The outcomes of the project will be: (1) the creation of effective COVID-19 educational interventions; (2) the provision of health-related information recommendations and resources to guide non-profits and other community groups who wish to educate the public; (3) the development of increased individual and community capacity to identify the differences between trustworthy and untrustworthy information on the virus; and (4) the mitigation of misinformation related to COVID-19. To reach these outcomes, we will rapidly develop and deploy COVID- 19 educational interventions in a variety of cultural contexts. We will test and improve these interventions based on empirical data from a variety of sources including focus groups, surveys, social media, and field research. Instruments, data, and resources will be shared on an interactive website with licenses that allow others to reuse them for free.",2020,-99,Royal Roads University,355796.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00081,170366,What is the public health risk communication response to COVID-19 in the context of social media?,"Keeping Canadians safe requires a robust public health system. This is especially true when there is a public health emergency, like the novel Coronavirus outbreak. Social media, like twitter and Facebook, is an important information channel because most people use the internet for their health information. The public health sector can use social media during emergency events for: 1) public health messaging, 2) monitoring misinformation, and 3) responding to questions and concerns raised by the public. In this study we ask: What is the public health risk communication response to an emergency infectious disease in the context of social media? We examine how provinces and provincial public health leaders, and the Public Health Agency of Canada and national public heath leaders engage with the public using social media during the Coronavirus event. We compare findings to provincial and national public heath social media activity before the emergency. We also compare findings to the gold standard - WHO social media activity during the emergency. Using our study findings, we will work with public health stakeholders to collaboratively develop a much- needed Canadian social media emergency response set of guideline recommendations for public health and other health system organizations.",2020,-99,Western University,96527.43,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00082,unknown,Research on development of diagnostic tests for the novel coronavirus disease (COVID-19),"The research group will aim to develop the basic technology for use in rapid diagnostic test kits for SARS-CoV-2. The group will focus on molecular and antibody based diagnostic technologies such as RT-LAMP, SARS-CoV-2 antigen detection assay, and anti-viral antibody detection assay. The group will also conduct viral genome analysis using clinical samples to develop robust diagnostic tests for SARS-CoV-2",2020,2019,"National Institute of Infectious Diseases, Japan",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2019 +C00083,unknown,Research on replication mechanisms and anti-viral therapeutic agents of the novel coronavirus,"Based on the elucidation of the infection mechanism and structural biological data, and also through library screening, the research group will search for infection-inhibitory molecules that suppress viral infection with the aim to develop new therapeutics.",2020,2019,"National Institute of Infectious Diseases, Japan",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2019 +C00084,unknown,Research on development of vaccines of the novel coronavirus disease(COVID-19),The research group will aim to develop a new vaccine by combining adjuvant and antigen vaccine using recombinant protein synthesis.,2020,2019,"National Institute of Infectious Diseases, Japan",,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies,2019 +C00085,unknown,Study on the control of a novel coronavirus (2019nCoV),"The research group will 1) develop animal models for 2019-nCoV, 2) verify the usefulness of human monoclonal antibody established from 2019-nCoV-infected patients, and 3) prepare a gene vaccine that encodes the spike (S) protein, a coronavirus protective antigen. The effectiveness of the vaccine will be verified by using animal models.",2020,2019,"Institute of Medical Science, The University of Tokyo",,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Pre-clinical studies,2019 +C00086,unknown,Study on multicenter open-label randomized clinical trial of favipiravir to evaluate the viral load reduction effect in asymptomatic and mild patients with SARS-CoV2 infection/A multicenter observational study to evaluate the clinical course of moderate and severe patients receiving favipiravir,"Favipiravir is an antiviral drug created by Toyama Chemical Co., Ltd. (Fujifilm Toyama Chemical Co., Ltd.) It was approved by the Ministry of Health, Labor and Welfare in March 2014, limiting the indications and effects to ""emerging or re-emerging influenza virus infections (only if other anti-influenza virus drugs are ineffective or insufficiently effective)."" The mechanism of action is that triphosphorylated form (T-705RTP) converted in vivo selectively inhibits viral RNA polymerase, so it is expected to be effective against RNA viruses other than influenza virus, but there is no evidence of utility for SARS-CoV2 infection. The aim of this research is to clarify the usefulness of favipiravir for asymptomatic and mild patients with SARS-CoV2 infection and the clinical course of moderate and severe patients receiving favipiravir by Specified Clinical Research",2020,2019,"Fujita Health University Hospital, Japan",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Prophylactic use of treatments,2019 +C00103,170706,Clinical Characteristics and Outcomes of Children Potentially Infected by SARS-CoV-2 Presenting to Pediatric Emergency Departments,"The manifestations of COVID-19 in children are not yet well understood, and may be atypical when compared to adults. We propose to carry out a two-year global prospective study that will enroll and follow-up children with suspected COVID-19 from 50 participating emergency departments (ED) across 19 countries. Patient epidemiological and demographic information, clinical characteristics, and disease outcomes, will be collected at the time of ED admission, during the course of illness, and at three weeks and three months after enrollment, using WHO-compliant case report forms. Statistical analysis of the collected data will allow for the identification of risk factors associated with children having confirmed SARS-CoV-2 infection, and/or severe COVID-19 outcomes. In order to enable rapid implementation, this study will be built as a parallel study that borrows the infrastructure from an ongoing study - the called Pediatric Emergency Research Network (PERN)-Pneumonia study, which has ethics approval, a centralized database, data sharing agreements, and established study teams that are actively enrolling children in 70 sites worldwide. Our multidisciplinary team of investigators includes pediatric infectious disease and emergency medicine clinicians, epidemiologists, statisticians, and public health leaders (from PHAC and the CDC), all with extensive experience pertaining directly to the research topic. As data will be shared in real-time with appropriate national and international authorities, this study will enable policymakers to make rapid evidence-based adaptations to case screening and management procedures that will then allow for the earlier identification of children at high risk of SARS-CoV-2 infection and severe COVID-19 outcomes. Furthermore, the establishment of this global multi-site study will be the first trial of a rapid PERN response to a novel virus, which, applying lessons-learned, can be urgently reactivated for future public health emergencies.",2020,-99,University of Calgary,587403.23,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Eastern Mediterranean | Europe | Western Pacific,,,,Canada,United States of America | Canada | Australia | Spain | United Kingdom | New Zealand | Austria | Belgium | France | Germany | Hungary | Israel | Italy | Latvia | Lithuania | Malta | Portugal | Qatar | Romania | Saudi Arabia | Sweden | Switzerland | Netherlands | Turkey,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C00104,"170560, 171487",Host Response Mediators in Coronavirus (COVID-19) Infection [Added supplement: Sex as a biological variable supplement],"The coronavirus (COVID-19) epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. WHO and others are launching clinical trials of novel anti-virals. We have a unique opportunity to complement trials of anti-virals with investigation of modulation of the human host response to improve outcomes of COVID-19. We are proposing to ""repurpose"" a class of drugs (ARBs) for hypertension (high blood pressure) that have been shown to prevent lung injury in influenza and could work on corona because influenza and coronavirus bind to the same cell receptor in the lung. ARBs are commonly prescribed for high blood pressure (50-70% of patients). To date, there have been no clinical studies of ARBs in COVID-19. We call our study ARBs CORONA. We believe that ARBs can decrease the severity of COVID-19 and mortality of hospitalized COVID-19 infected adults. We will evaluate safety and effectiveness of available ARBs in COVID-19 in a multicentre study of 497 hospitalized adult patients who are or are not already on ARBs. Key personnel are in place to expedite this study. If this study is successful, ARBs can potentially limit complications and mortality of COVID-19. Potential results: ARBs are inexpensive clinically available cardiovascular drugs. If this study is successful, ARBs can potentially be used globally to limit complications and death due to COVID-19.",2020,2021,University of British Columbia,214131.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00105,170656,Therapeutic Development for COVID-19 Coronavirus Induced Sepsis and ARDS Targeting Vascular Leakage,"The new coronavirus COVID-19 is threatening to become a global pandemic for which currently no effective drugs exist. Although development of vaccines and drugs targeting the virus are ramping up, none of these addresses host response of COVID-19 infections directly. CAVID-19 death is mainly caused by Acute Respiratory Distress Syndrome (ARDS), which arises from a dysregulated host immune response and associated vascular leakage from viral induced sepsis. Our proposed drug development efforts aim to control the host response and protect patients from ARDS and death. My lab developed a novel zebrafish sepsis model to screen and identify drug compounds that rescue sepsis-associated mortality and vascular leakage. This project will pursue two main research objectives: (1) develop our best anti-sepsis candidate drug UNC0642 for treatment of COVID-19 induced sepsis/ARDS, and (2) carry out drug screens to identify and repurpose existing drugs as anti-COVID-19 therapeutics. UNC0642 inhibits G9a and GLP enzymes responsible for gene regulation. Severe viral infection leads to an immune over-response which drives vascular leakage and results in multiple organ swelling and ARDS. We hypothesize that UNC0642 will protect coronavirus patients from organ swelling and decrease ARDS and mortality by controlling immune-associated gene expression. Dr. Wen has extensive expertise in virology, transgenic animal modelling, clinical medicine and drug development needed to carry out the proposed project. A collaboration with Dr. Samira Mubareka is in place to start COVID-19 virus work at University of Toronto's CL3 lab. Once developed, UNC0642 will become a first line treatment of severe COVID-19 infection. Because of the tragic outbreak of COVID-19 infection in China, regulatory filing for clinical trials in China are likely expedited, especially for repurposing existing drugs. COVID-19 mouse and zebrafish models developed will be rapidly shared with other coronavirus research groups.",2020,-99,Unity Health Toronto,710441.71,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Western Pacific,,,,Canada,Australia,"Therapeutics research, development and implementation",Pre-clinical studies, +C00106,170640,"Automated Oxygen Titration, Monitoring and Weaning in patients with infectious pneumonia requiring oxygen - impact on the number of interventions for healthcare workers. An innovative device to manage patients with COVID-19 pneumonia. COVID study (Closed-Loop Oxygen to Verify that healthcare workers Interventions Decrease during pneumonia)","Automated oxygen titration, weaning and monitoring (FreeO2 device) may be a solution to reduce the number of interventions of healthcare workers (which is directly related to the risk of transmission of COVID-19. There is a high risk of transmission of COVID-19 to healthcare workers. in a recent cohort, 29% of the patients hospitalized were healthcare workers. Among the main WHO's strategic objectives for the response to COVID-19, the first was to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers. Every measures that potentially reduce the number of interventions during the management of patients infected by COVID-19 should be evaluated. Oxygen therapy is the first line respiratory support in all patients hospitalized for COVID-19 during initial management. Recent recommendations are to accurately titrate oxygen to avoid hypoxemia and complications-related to hyperoxia (local and systemic inflammation, vasoconstriction through reactive oxygen species production, acute myocardial infarction). In addition, around 1/3 of the patients will deteriorate their clinical condition and require admission to intensive care units; consequently, a close monitoring is required during initial management. We will conduct a randomized controlled study comparing Automated oxygen titration and monitoring (FreeO2) vs. Manual oxygen titration and weaning in patients hospitalized for infectious pneumonia requiring oxygen therapy. The patients will be included in Canadian sites within the first 3 days of admission and will be evaluated during 24 consecutive hours, including 4 hours at bedside. Two hundreds and sixteen patients will be included in the study. The primary endpoint will be the number of interventions for oxygen management Secondary endpoints will include the oxygenation parameters and the oxygen consumption.",2020,-99,Institut universitaire de cardiologie et de pneumologie de Québec - Ulaval,617826.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management, +C00107,"170630, 175533",Development of a portable point-of-care device for rapid testing of SARS-CoV-2 [Added supplement: COVID-19 Variant Supplement],"The novel coronavirus (SARS-CoV-2) outbreak that started in December 2019 triggered unprecedented measures to avoid a global pandemic. However, China has been particularly hit with over 70 000 confirmed cases, of which about 80% are in Hubei province. Wuhan, capital city of Hubei, is considered ground zero of the outbreak. Testing is typically performed at centralized facilities with highly qualified personnel operating specialized equipment, RT-qPCR being the current method of choice and DNA sequencing a second choice. The response time between sampling patients and obtaining clinically relevant information usually depends on sample shipping time and clinical lab capacity. In this current outbreak containment situation in China, large portions of the population are quarantined, travel is restricted, and clinical labs are operating well over capacity. We propose to develop a rapid point-of-care test to help mitigate the outbreak of COVID-19. The RNA-based test will be performed with a high sensitivity, label-free sensing method. RNA purification and amplification will not be required. The instrumentation needed will be portable and lightweight to enable frontline workers to rapidly test for SARS-CoV-2. The assay will be developed with an easy-to-use platform that can be operated by untrained personnel. It can thereby be deployed locally, within regions of quarantine at a temporary health centers and neighbourhood clinics, reducing flow of people in urban centers; it can be shipped and used in remote or isolated areas including cruise ships",2020,2022,Université Laval,739500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00108,"170638, 171484",Reducing the Health Care Resource Burden from COVID-19 (SARS-CoV-2): Rapid Diagnostics to Risk-Stratify for Severity of Illness [Added supplement: Sex as a biological variable Supplement],"Key to an effective response to the current novel coronavirus (COVID-19) outbreak is a method to rapidly identify emergency department patients presenting with symptoms of COVID-19 and are at high risk of progressing to severe illness and death. At University Health Network, our team represents a deeply experienced group of critical care doctors and infectious disease researchers who can immediately respond to the global need to provide an accurate diagnosis of respiratory illness-the main feature of COVID-19-at the front lines of patient care. We have recently developed a 40 minute diagnostic test to determine lung quality for transplantation. Recent scientific studies from China clearly show that the body's development of respiratory distress as a response to potential COVID-19 infection produces an identical injury profile that would be detected by our diagnostic test. We will work alongside SQI Diagnostics, our Canadian partner committed to developing diagnostics for lung health, to adapt our test towards the development of RALI-Dx (Rapid Acute Lung Injury Diagnostic). This diagnostic can be used by hospital emergency departments to screen for lung sickness and the likelihood of COVID-19 infection. An important part of our CIHR-supported research study is a commitment from our Chinese collaborators to safely test our diagnostic first on COVID-19+ blood samples to make sure the test is highly accurate before hospital use. With our 40 minute RALI-Dx test, we will: -Quickly identify the highest risk patients in need of immediate care -Identify lower risk patients who require at-home monitoring -Reduce the current major stress on health care facilities Additionally, new COVID-19 therapies are being rapidly developed around the world, and the first step will be to identify which patients will benefit the most from these treatments. With RALI-Dx, hospitals everywhere can better manage patient care and provide an accelerated response to the COVID-19 outbreak.",2020,2022,University Health Network,714491.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00109,170654,Plasmonic PCR: Rapid Point-of-Care COVID-19 Diagnostic Platform.,"The recent outbreak of the coronavirus COVID-19 pandemic clearly demonstrates how in today's age infectious agents can spread rapidly. Given the ability of individuals to travel across the globe infectious agents can reach pandemic/epidemic proportions quickly, as seen with SARS and MERS outbreaks. Such viral agents become infectious because of genetic alterations many times occurring in other animals and eventually can infect humans. There are no effective anti-viral agents nor have vaccines been developed. Thus during these outbreaks we can only rely on infection control measures. Such measures help control the spread of the disease but is dependent on verifying individuals who are infected and those who are not infected. Presently diagnosing COVID-19 infections is inadequate as the laboratory tests may take 24-48 hrs to be completed. Such time periods make infection control very difficult. In this proposal we discuss how a rapid testing and diagnosis be made in the order of minutes. We have developed a revolutionary methodology that would construct a diagnostic device which is small and portable, and even be battery operated. Our device would be a true point of care platform that would be used at the ""first contact"" between patient and health professional. Our point of care testing platform would give rapid result in minutes and would help enormously in infection control management of not only the current COVID-19 outbreaks but also future pathogenic viral outbreaks which are surely to happen.",2020,-99,Institute for Medical Research (Mtl),511268.73,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00110,170655,SARS-CoV-2 Rapid Research: Fast track isothermal viral diagnostics,"COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With no treatment or vaccine currently available, it is imperative that rapid, sensitive, and simple screening technologies be developed that can be fully integrated into near real time medical reporting infrastructure so as to speedily identify viral carriers and slow this and future viral outbreaks. The Unrau laboratory at Simon Fraser University has engineered an isothermal RNA detection kit that reports the presence of RNA template by fluorogenic aptamer (RNA Mango) synthesis in a simple fluorogenic assay (Mango NASBA). This technology, which currently is being commercialised for the detection of pathogens in human tissue culture, can be rapidly adapted for the detection of SARS-CoV_2 and offers several advantages over conventional RT-PCR: 1. Isothermal Mango NASBA viral testing has a considerably simpler work flow than RT-PCR requiring only a simple fixed temperature device capable of detecting fluorescent readout. This offers the potential to implement real time viral testing at venues (i.e. airports, borders, hospitals etc) not normally considered with existing RT-PCR methodologies and that require more costly real-time thermocycler infrastructure to implement. 2. We anticipate that Mango NASBA offers a significant time saving of ~3-4 fold relative to a standard RT-PCR assay (90-120 min) in high viral load samples. Should high sensitivity detection be required, Nested Mango NASBA can be performed subsequently. Nested Mango NASBA has sensitivity directly comparable to RT-PCR and can be performed twice as fast as RT-PCR methodologies. We have assembled a team consisting of biochemists, chemists, virologists, engineers, and clinicians offering deep skills in four highly significant fields to help address this rapidly evolving SARS-CoV_2 crisis. This highly expert team will meet the challenge of detecting and tracking this rapidly evolving viral outbreak.",2020,-99,Simon Fraser University,368281.6,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00111,170703,Development of field-deployable and point-of-need diagnostics for SARS-CoV-2 using CRISPR-based technology,"Current diagnostic testing for the SARS-CoV-2 outbreak requires the use of specialized equipment for molecular-based pathogen detection. The equipment must be housed in a facility with electricity and freezers for storage of temperature sensitive materials and equipment operation. Lateral flow based assays are an alternative diagnostic tool that is inexpensive, temperature stable, user-friendly and has a faster turn-around-time (TAT). However, this platform takes longer to develop, with reduced specificity, sensitivity, and accuracy compared to molecular-based assays. An ideal diagnostic tool combines the adaptability and reliability of molecular assays with the TAT, cost-effectiveness, and stability of lateral flow. Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) based diagnostics can provide these capabilities and revolutionize the field of point-of-need molecular-based diagnostics. Our goal is to develop CRISPR-based diagnostics to detect SARS-CoV-2 at the point-of-need, such as at the bedside, passenger screening, or returning travellers who may have been exposed. We recently demonstrated that CRISPR-based diagnostics is reliable, sensitive and can be used to detect Ebola virus and Crimean-Congo hemorrhagic fever virus. SARS-CoV-2 is highly contagious and caused more than 69,000 infections and contributed to over 1600 deaths. Therefore, it is of utmost importance to quickly diagnose SARS-CoV-2 infection to administer appropriate patient care and isolation. CRISPR-based diagnostics is a next-generation diagnostic tool that can provide results in a timely manner and fill this gap. Implementation of CRISPR-based diagnostics will complement our armamentarium against high-consequence pathogens and will address the need for faster, cheaper, and more robust diagnostics for emerging infectious diseases of public health concern.",2020,-99,Canadian Science Centre for Human and Animal Health (Winnipeg),293368.66,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Manitoba,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00112,170705,Rapid RNA sequencing of coronavirus for public health surveillance and transmission,"There is an ongoing worldwide outbreak of the COVID-19 coronavirus. As of February 18 2020, nearly 73,500 cases have been identified and 1,875 deaths reported. To prevent further spread and to understand how the COVID-19 virus is spreading, where it came from, and when it likely jumped from animal to humans, the genome sequences of these viruses have been instrumental in providing insights. So far, Canada has reported 8 cases of COVID-19 (5 in BC; 3 in ON). However, no Canadian genomes have been made publicly available. In contrast, over 102 genomes have been released from several other countries including China, Taiwan, Japan, Australia and the United States. Here, the Public Health Laboratory in Alberta, Edmonton and Calgary and the National Microbiology Laboratory in Winnipeg have teamed up with genomics, bioinformatics, microbiology and infectious disease experts to address this challenge. We are verifying a direct RNA sequencing method capable of accelerated inexpensive sequencing of COVID-19 virus genomes. We aim to roll out this rapid method into Canada's frontline operations, along with direct analysis to promote global sharing and uptake of needed genome information. The lab methodology and data analysis will be openly available to help the global response in combating this disease.",2020,-99,University of Alberta,561376.91,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C00113,170657,LabAnywhere: Technology for Detection of Coronavirus in Remote Settings,"The COVID-19 disease is caused by a virus. Since the symptoms of the COVID-19 disease are similar to many other illnesses, accurate detection and correct identification of the virus in a patient is important to know whether or not the patient is suffering from COVID-19 versus another disease. The current gold-standard detection uses sophisticated molecular biology that must be done in a laboratory by trained technicians. Our research team has developed LabAnywhere, a system intended for rugged use in agriculture. Its called LabAnywhere because it is designed for use in a barn or farm field where there may not be any clean enclosed space to do complex sample handling. The viruses are different in veterinary medicine, but with some modifications, the technology can be applied to human diseases in remote settings. The proposed research will piggyback upon existing projects. The research team; a design engineer, along with experts in medical biophysics, protein chemistry, and veterinary diseases have been testing a pen-side system for the livestock industries. The design is a simple, easy to deploy handheld system for a molecular biologic assay where there is no laboratory available, such as on a ship at sea or in a remote community many days travel from a laboratory. The project will use easily handled, safe viruses from the animal world for initial testing to validate the methods, then move to tests using human viruses once initial trials are complete.",2020,-99,University of Prince Edward Island,253591.28,Animals | Viruses,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C00114,"170629, 175564, 175494, 171486","Innovative therapeutic approaches for the 2019-novel coronavirus [supplements: COVID-19 Variant Network, COVID-19 Variant Supplement, sex as a biological variable supplement]","The 2019-novel coronavirus (SARS CoV-2) is a major sanitary and economical threat to all countries. Development of effective antivirals is a major global priority especially early in the epidemic when vaccines are unavailable. This proposal aims at discovering and evaluating active compounds by rational design through 3D modeling of key viral proteins and also by analyzing cellular gene signatures induced by the virus. In-depth evaluation of selected compounds will include in vitro, ex vivo (human bronchial epithelium tissues) and in vivo (animal models) studies. These approaches, mostly based on drug repurposing (new indication for an existing drug), will result in rapid identification of anti-SARS CoV-2 compounds with accelerated clinical development.",2020,2022,CHU de Québec,779937,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00115,"170631, 171494",Augmented Discovery of Potential Inhibitors of SARS-CoV-2 3CL Protease [Added supplement: Sex as biological variable supplement],"The COVID-19 epidemic is causing serious or even fatal respiratory tract infections around the city of Wuhan, China and other countries. The urgent situation is pressing the global community to respond rapidly together to develop a vaccine or small molecule drug to inhibit viral infection. We have recently established a powerful Deep-Learning accelerated Docking pipeline to virtually screen a commercial 1.3-billion-compound library in a matter of one week--compared to the three years with previous programs. We have applied this novel algorithm to identify 1000 quality ""candidate"" compounds to inhibit the SARS-CoV-2 main protease (3CLpro) which is uniquely critical for the viral life cycle. We will screen these compounds with a high throughput screening biochemical assay and then evaluate these hits using a cell-based SARS-CoV-2 viral replication assay in a Canadian Containment Level 3 facilty at University of British Columbia. In addition we will use X-ray crystallography to refine the protease 3D crystal structure to accelerate the development of COVID-19 therapeutic drug development. Our research program will significantly contribute to global response to the COVID-19 outbreak by rapidly identifying small anti-viral drug molecules in an extremely condensed timeframe. Our expertise, facilities, and capabilities in cutting-edge Artificial Intelligence, inhibitor modeling, X-ray crystallography, coronavirus protease inhibition, human viral pathogen research, and anti-viral therapeutics are world class. Our first application this month of ""Deep Docking"" enabled the screening of 1.3B commercially available compounds against the essential SARS-CoV-2 protease, in 1 week compared to the 3 years of conventional docking. This accomplishment coupled with fast tracking anti-viral assays at UBC and high resolution 3D structure characterization provide our team, Canadians and global colleagues an enormous head start on developing an anti-viral therapeutic for COVID-19",2020,2022,University of British Columbia,734300,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00116,"170649, 175552",Neutralizing Antibodies as SARS-CoV-2 Therapeutics [Added supplement: COVID-19 Variant Supplement],"Three highly virulent coronaviruses - SARS-CoV, MERS-CoV and SARS-CoV-2 - have crossed species barriers to infect humans since 2003. SARS-CoV-2 is responsible for COVID-19, a disease that arose in Wuhan China in December of 2019. The virus has infected over 64,000 people and caused 1380 deaths and the World Health Organization has declared it a public health emergency of international concern. Although drastic measures are being taken to contain SARS-CoV-2, there is an urgent need for new therapeutics to combat this virus and reduce its spread. In this work we will develop therapeutics based on human antibodies that can be used in the treatment of COVID-19.",2020,2022,University of Toronto,414222.6,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00117,"170636, 171493, 175518","Host cellular protein substrates of SARS-CoV-2 proteases [Added supplements: Sex as biological variable supplement, COVID-19 Variant Supplement]","The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to COVID-19 disease in China and worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Currently, the pathogenic mechanisms that lead to COVID-19 and related SARS/MERS-CoV diseases are not understood. In this study, we will identify the host proteins that are targeted by a viral protein called a protease using an unbiased proteomics approach. Identifying the protein targets of SARS/MERS-CoV proteases will reveal into the protein sequence that binds to the proteases. We will engineer and optimize decoy protein sequences that will effectively block SARS/MERS-CoV protease function and thus, inhibit SARS/MERS-CoV infection. Uncovering the proteins that are targeted by the SARS/MERS-CoV proteases will also provide a catalog of the host processes that these viruses affect, thus gaining insights into the pathogenic mechanisms that lead to COVID-19 disease.",2020,2022,University of British Columbia,306348.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00118,"170362, 171483, 175543","Drug repurposing for the rapid development and evaluation of SARS-CoV-2 antivirals [Added supplements: Sex as biological variable supplement, COVID-19 Variant Supplement]","The initial symptoms of COVID-19 are fever, shortness of breath and a dry cough. For some patients, the disease progresses to pneumonia as the infection spreads to the lung and leads severe inflammation. These severe symptoms can cause difficulties for the lungs to oxygenate the blood and can lead to death. There are currently no antivirals against SARS-CoV2, the causative agent of COVID-19, and development of new molecules can take years to reach patients. As the COVID-19 epidemic is progressing rapidly, the need for antiviral therapy is urgent. Therefore, our goal is to use our current arsenal of approved drugs already tested for their safety and used in the clinic for various conditions and repurpose them to treat COVID-19. In this rapid response grant, we propose to identify drugs with activity against SARS-CoV2 in vitro and in vivo and contribute to the global COVID-19 response and provide a therapeutic option for patients developing life-threatening disease.",2020,2022,University of Ottawa,358480.2,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C00119,"170658, 175510",Targeting genetic and chemical vulnerabilities of novel coronavirus SARS-CoV-2 [Added supplement: COVID-19 Variant Supplement],"The recent outbreak of the SARS-CoV-2 coronavirus in China and its continued international spread threatens to become a global pandemic. Although coronaviruses generally cause mild respiratory infections in humans, over the past 18 years, three animal-derived coronaviruses have emerged that cause much more severe disease: SARS-CoV, MERS-CoV, and the current SARS-CoV-2. Each of these emergent viruses cause substantially higher death rates than common coronavirus infections; the current estimate of the death rate due to COVID-19 syndrome caused by SARS-CoV-2 infection is ~2.5%. The main challenge in addressing these new coronavirus-associated outbreaks is a lack of suitable therapeutics to treat active disease (i.e., anti-viral drugs) or to prevent disease (i.e., appropriate vaccines). We propose to apply genomics-based tools and drug-screening platforms to rapidly pinpoint new targets for SARS-CoV-2 anti-viral agents and to identify candidate therapeutic compounds. Our team has deep expertise in anti-infective drug discovery, the application of genomics in identifying drug targets, and in the biology and biochemistry of RNA viruses such as SARS-CoV-2. Our project will identify new therapeutic strategies that may help to treat COVID-19 patients. These strategies will also help mitigate newly emergent coronavirus-associated diseases that will undoubtedly continue to cause outbreaks in the future.",2020,2022,McMaster University,727392.8,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00120,"170644, 175505",Development of COVID-2019 main protease inhibitors as potential antivirals against the 2019 coronavirus. [Added supplement: COVID-19 Variant Supplement],"Coronaviruses are associated with a variety of human diseases ranging from the common cold to new and serious conditions such as Severe Acute Respiratory Syndrome (SARS), which emerged in 2002, Middle Eastern Respiratory Syndrome (MERS), first reported in 2012, and a recent and still growing outbreak of COVID-19, caused by the coronavirus SARS-CoV-2. MERS and SARS together claimed over 1600 lives, and the death toll of COVID-19 recently passed 1300 and is growing rapidly. It is currently unclear if the COVID-19 outbreak can be contained, with some estimates of potential fatalities reaching as high as 50 million. There is currently no approved treatment for any coronavirus, although clinical trials of the Gilead compound Remdesivir are currently underway and there is some optimism that it may be effective against SARS-CoV-2. Nevertheless, there is an urgent need for additional potential SARS-CoV-2 therapeutics, as the success of Remdesivir is far from assured. We are proposing to use a combination of computer calculations and laboratory testing to rapidly identify and validate molecules that block an enzyme that is essential to the virus. The targeted enzyme, known as 3CLpro, is responsible for processing viral proteins into their active forms. A detailed 3D structure of the SARS-CoV-2 3CLpro enzyme was recently solved, and this provides enough information to identify chemical structures of molecules that are likely to block its action, through a procedure known as virtual screening. We will synthesize promising compounds and test them against the purified enzyme using a technique known as Isothermal Titration Calorimetry (ITC). Our team has a proven track record of using virtual screening and ITC to generate potent inhibitors of enzymes similar to 3CLpro. Molecules we identify are likely to prevent the virus from replicating and would have high value as new potential treatments for COVID-19 that could be used alone or in combination with other therapies",2020,2022,McGill University,181600,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00121,"170709, 175534",Targeting programmed ribosomal frameshifting as a therapeutic strategy against 2019-nCoV [Added supplement: COVID-19 Variant Supplement],"The new coronavirus 2019-nCoV has spread rapidly in the last 3 months, infecting tens of thousands of people in dozens of countries and killing over 1,000, with no preventive vaccines or medications that can treat it. We propose to search for possible drugs to treat 2019-nCoV by targeting the ability of the virus to hijack the cell's machinery and recode how the genome is read via programmed ribosomal frameshifting (PRF). Coronaviruses use PRF, which is triggered by a specific structure (a 'pseudoknot') in the viral genome, to produce essential enzymes in specific ratios. Suppressing PRF in SARS coronavirus-which is very closely related to 2019-nCoV-disrupts viral propagation and significantly reduces infectivity, suggesting that PRF inhibitors could be used to combat 2019-nCoV. We will search for potential drugs that bind to the 2019-nCoV pseudoknot and disrupt PRF. We will first build a structural model of the pseudoknot by combining computational simulations with measurements revealing the base-pairing patterns and higher-order structures in the RNA. We will then use high-throughput computational tools to screen large libraries of existing approved drugs (which could be deployed rapidly), as well as publicly-available chemical compounds, for binding to the pseudoknot. Compounds predicted to have high binding affinity will be tested experimentally to confirm their binding-quantifying the binding affinity, identifying the binding site, and showing that binding alters the pseudoknot structural dynamics (thought to be important for triggering PRF)-and to measure their effectiveness at inhibiting PRF in cell extracts. We will examine if the effects of the compounds are specific to 2019-nCoV by repeating all measurements using other RNA structures as controls. Lead compounds will be passed on to collaborators for future studies assessing their effectiveness against live virus and suitability for deployment as therapeutics.",2020,2022,University of Alberta,363184.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00122,170659,Repurposing of FDA-approved drugs as novel therapeutics for COVID-19,"Currently, there is no vaccine or effective therapeutics for COVID-19, which is caused by 2019-nCoV (now officially referred to as SARS-CoV-2). Tens of thousands of people get infected by SARS-CoV-2 and substantial percentage of them showed severe symptoms. Dr Wu's team proposed to rapidly screen database of FDA-approved drugs by computationally approaches and further evaluate the top-ranking candidates by an array of experimental assays. This project could rapidly lead to drug candidates for COVID-19.",2020,-99,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,340513.38,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies, +C00123,"170627, 171492, 175507","Neutralizing human-derived single-chain antibodies against SARS-CoV-2 [Supplements: COVID-19 Variant Supplement, Sex as a Biological Variable supplement]","SARS-CoV-2 is a virus that has caused an epidemic of human respiratory disease (COVID-19). It first emerged from the city of Wuhan in Hubei in December 2019 and has since spread widely in China and to more than 24 counties globally. The virus has been declared as a deadly global threat, and accelerated international efforts have been engaged to control the virus. A total of 1,524 deaths been confirmed as of 15th February 2020 (WHO). As a result of the rapid transmission internationally, a global call to control the spread of the virus in affected and non-affected areas has been implemented. Currently, there is no effective treatment or vaccine to control the virus. Symptoms of the infection include respiratory symptoms, fever, cough, and shortness of breath. In more severe cases, the infection can cause respiratory failure, severe acute respiratory syndrome, kidney failure, and death. The objectives of this application are 1) to develop antibodies that will block the entrance of the virus into the cells, and to test the efficacy of these antibodies in mice.",2020,2022,University of British Columbia,351420,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00124,"170707, 175508",Towards anti-COVID-19 therapeutic development by targeting the viral papain-like proteinase [Added supplement: COVID-19 Variant Supplement],"When positive-stranded RNA viruses such as the causative agent for the 2019-2020 novel coronavirus (SARS-CoV-2) outbreak enter an infectious cycle in the cell, their RNA genomes hijack the host cell's protein production machinery to mass produce large continuous viral polyproteins in a process called translation. In order to make progeny viruses, these viral polypeptides need to be processed into smaller, individually functional protein programmed to perform specific tasks, e.g., replicating the RNA genome, assembling the protein coat for progeny viruses, packing the newly synthesized RNA genome into the assembled viral capsid, and subverting or disabling the host cell's antiviral defense mechanisms. Two virally encoded proteinases, the papain-like (PL) and the 3C-like (3CL) proteinases, carry out the job of ""clipping"" the viral polypeptides into individual viral proteins. The PL is translated before the 3CL hence it likely takes precedence in performing ""cuts"" in the polyprotein, releasing an initial batch of viral proteins to mount the first wave of suppressive attack on antiviral host defense. In addition, coronavirus PL directly participates in preventing type I interferon activation, an important step leading to antiviral defense. Last but not the least, PL1 is part of non-structural protein 3 (NSP3), which is an indispensable component of the membranous complex where viral RNA genome is replicated. Taken together, PL of the novel coronavirus makes a good antiviral target for the development of therapeutics. Inhibiting PL would not only halt viral protein and RNA production at an early stage but would also help restore host antiviral defense. In this proposal, we seek to solve the 3-dimensional structure of SARS-CoV-2 PL and then use the structural knowledge to aid our search of small molecules that can inhibit the functions of PL. We will work with our collaborators to optimize the top inhibitors and test these inhibitors in cell and animal infection models.",2020,2022,University of Alberta,257200,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00125,170645,SARS-CoV-2 pathogenesis in human and bat cells and development of in vitro and in vivo infection models,"Severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) emerged in December 2019 and has infected over 60,000 people, of which over 1800 have died. SARS-CoV-2 shares 96% similarity with a coronavirus found in bats. Bats have been shown to carry a diversity of viruses including coronaviruses globally, without showing signs of disease. Also, major circulating and endemic coronaviruses that are causing disease in humans are speculated to have evolved in bats. Our team's extensive experience in studying coronaviruses in bat and human systems, will allow us to understand interactions of SARS-CoV-2 in bats and humans using a holistic 'One Health' approach. The main objectives of our proposal are to investigate how cell anti-viral responses are induced in human (spillover host) and bat (reservoir host) cells, and to develop animal models to facilitate rapid testing of vaccine candidates and therapeutics.",2020,-99,McMaster University,561348.41,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Animal source and routes of transmission | Immunity | Disease models, +C00126,170652,COVID-19 Ring-based Prevention trial for Undermining Spread (CORPUS),"Despite efforts to contain COVID-19, the potential for a global pandemic necessitates the rapid evaluation of strategies for prevention of COVID-19 in close contacts of new cases. Lab data, animal models and early clinical data suggest that a drug commonly used to treat HIV, called Kaletra, may have activity against COVID-19 and its closely related ""cousin"" coronaviruses, SARS and MERS. Kaletra is currently being tested in clinical trials in China for treatment. This drug has been safely used for over two decades in HIV treatment and also in post-exposure prophylaxis (PEP) for un-infected people with high-risk exposures. We propose a study that will address the immediate need for prevention interventions by testing whether or not giving Kaletra PEP to contacts exposed to COVID-19 will stop them from getting the disease. We expect to test this in three key groups of exposed contacts: the frail elderly in nursing/retirement homes, frontline health workers, and household/community contacts. Our trial employs a commonly used approach in vaccination studies called a ring design, which also allows us to collect detailed information about the natural history of the infection in exposed contacts. In addition to testing the effectiveness of our specific intervention, the master protocols and procedures developed can be used to test other prevention interventions including both medications and vaccines, once they become available. This ring design was a key part of the successful eradication of smallpox, and the evaluation of the vaccine used for Ebola. We will identify a ring of exposed close contacts around index cases and randomize these rings to a 14-day course of Kaletra PEP or a placebo control and will test contacts systematically to see if they develop COVID-19. Our study team members of Canadian experts on the frontlines with SARS, MERS, H1N1, Ebola, and HIV, are well connected to coordinate with existing clinical trials networks both in Canada and internationally.",2020,-99,Unity Health Toronto,712371.08,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C00127,170641,Understand the high pathogenicity and zoonotic transmission of the COVID-19 virus: evasion of host innate immune responses,"Coronaviruses are not new to humans. The human coronaviruses OC43 and 229E were discovered as early as in the 1960s. Both viruses cause common cold, a mild infection of our upper respiratory tract. However, the story started to change in 2002 when SARS broke out in China and other countries. This outbreak was caused by a new coronavirus which originally came from bats. Most importantly, this SARS coronavirus is highly pathogenic, with a fatality as high as 10%. Ten years later, a more deadly coronavirus caused the MERS outbreak. Now, a new coronavirus came back, is raging in China, may cause a global pandemic if not controlled. This new virus, COVID-19 (or SARS-CoV-2), has infected more and killed more than the total number by both SARS and MERS. Two urgent questions need to be addressed. How did these coronaviruses transmit from animals into humans? What have made them so pathogenic and lethal? Humans are protected from viral diseases by the immune system. These pathogenic coronaviruses must have found ways to evade the immune responses so that they can spread in humans and cause fatal illness. We thus propose this research to elucidate how this COVID-19 virus does this. The findings will identify the key viral genes that suppress immune responses by blocking essential signaling pathways. Our results will open new avenues for the development of effective interventions to halt the COVID-19 break.",2020,-99,Institute for Medical Research (Mtl),341938.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Animal source and routes of transmission, +C00128,"170367, 175542",Genomic epidemiology and evolutionary dynamics of COVID-19 and other emerging corona viruses [Added supplement: COVID-19 Variant Supplement],"Emergence of the 2019 coronavirus (SARS-CoV-2) has highlighted the severe impact emerging zoonotic pathogens have on human health, the global economy, and health service delivery. Phylogenetic analyses of SARS-CoV-2 genomic sequences improve our understanding of host reservoir species, assess the potential for transmission to humans, and illuminate evolutionary dynamics relative to other viruses in Coronaviridae, informing response to current and future epidemics. We will study the genomic evolution of SARS-CoV-2 to investigate if particular motifs are under selection for increased virulence and immune evasion. We will compare SARS-CoV-2 with genomes of other zoonotic coronaviruses to elucidate common genomic features associated with virulence, host switching, and human-to-human transmission. We will also evaluate spatiotemporal transmission patterns of SARS-CoV-2 across different populations using Bayesian phylogeographic analyses. Such analyses allow identification of spatially and temporally structured, clinical and epidemiological parameters such as the basic reproduction number, period of infectiousness, and true viral prevalence over time within different populations. We will also elucidate the reservoir host species of SARS-CoV-2 in concert with collaborators from the Chinese Centre for Disease Control as well as other Canadian researchers by probing unique environmental samples as well as both novel and existing datasets available for coronaviruses. Phylogenetic co-speciation analysis will explore whether coronaviruses are more likely to jump between phylogenetically proximate host species allowing development of a predictive framework to anticipate future zoonotic events. We will identify genomic factors of SARS-CoV-2 associated with virulence, estimate vital epidemiological parameters, and illuminate potential reservoir species. With the Chinese CDC, we will help focus the response, control and elimination of the current, and future, coronavirus outbreaks.",2020,2022,University of British Columbia,260000,Bacteria | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2020 +C00129,170643,Evaluation of Intervention Strategies in Response to the COVID-19 Outbreaks,"With the global spread of the novel coronavirus virus and potential for a COVID-19 pandemic, the World Health Organization declared a ""Public Health Emergency of International Concern"", recognizing an extraordinary event that requires coordinated efforts to contain disease outbreaks. Research to evaluate intervention strategies can help decision-makers to identify the type and intensity of control measures needed for containment. We propose to investigate the severity and healthcare resource utilization during potential outbreaks, estimate the transmissibility and the percentage of the population that could be affected, and predict clinical outcomes and critical care demand. We will use modelling and simulation for nearly real-time estimates of public health and healthcare interventions in Canada, the US and India. Our specific research objectives are to: 1) Predict the scope of disease transmission, potential outbreaks, and clinical attack rates. 2) Project what hospitals will require for isolation, ambulatory services, emergency and hospital admissions, and critical care of symptomatic patients. 3) Assess the potential effects of various non-pharmacologic interventions, including quarantine, self-reporting and isolation, and school closure. 4) Evaluate the effectiveness and cost-effectiveness of a COVID-19 vaccine and determine best scenarios to distribute a vaccine based on population age and risk of disease severity. To achieve these objectives, we will develop new and adapt existing mathematical models to simulate the transmission dynamics of COVID-19 in outbreak scenarios. Our team has access to a number of databases including daily reports on incidence of confirmed and suspected cases, hospitalization, and deaths attributed to COVID-19 in China. Using demographics of the Canadian, US, and Indian populations, we will evaluate the effectiveness of vaccination strategies, hospital surge capacity, and social policies such as quarantine and closing schools.",2020,-99,York University,188375.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Approaches to public health interventions, +C00130,"170646, 175577",Agent-based and multi-scale mathematical modelling of COVID-19 for assessments of sustained transmission risk and effectiveness of countermeasures [Added supplement: COVID-19 Variant Network],"The Fields Institute for Research in Mathematical Sciences, in collaboration with the Pacific Institute of Mathematical Sciences and the Atlantic Association for Research in Mathematical Sciences, together with the Public Health Agency of Canada and international partners, is assembling a national COVID-19 Mathematical Modelling Rapid Response Task Force. Our goal is to mobilize a national network of infectious disease modellers to develop mathematical technologies to assess transmission risk of COVID-19, project outbreak trajectories, evaluate public health interventions for its prevention and control, and inform public health policy makers as well as multi-scale modelling to assist in the development of effective treatment strategies. Such a network functioned during SARS and was successful in providing real-time advice to public health officials. In the case of COVID-19, in addition to the mathematical modellers drawn from across Canada, we have the partnership of the Public Health Agency of Canada and its Coronavirus Modelling Group, Vaccine and Infectious Disease Organization at the University of Sasketchawan, the Advanced Disaster, Emergency and Rapid Response Simulation facility at York University and several research institutes in China including one at Xi'an Jiaotong University.",2020,2022,"The Fields Institute for Research in Mathematical Sciences (Toronto, ON)",545666.9,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C00131,"170711, 175514, 175568","Production of a recombinant S ( spike ) protein vaccine against SARS-CoV-2 and emerging coronaviruses [Added supplement: COVID-19 Variant Supplement, COVID-19 Variant Network]","In December 2019 a human coronavirus (CoV) outbreak causing pneumonia-like symptoms began, centered around a fish market in the Wuhan district of China. After the genomic sequence was determined the causative pathogen, SARS-CoV-2, showed 99.98% identity among 9 patients, was 88% identical to two bat SARS-like CoV, ~79% identical to SARS-CoV, and ~50% identical to MERS-CoV (Tan 2020 Lancet). SARS-CoV and MERS-CoV were responsible for severe human illness and mortality (~10% in 2002 and ~35% in 2013, respectively). Although understanding of SARS-CoV-2 and the COVID-19 disease is ongoing, it is believed human-to-human transmission is possible and the disease fatality rate is ~2-3%. In early February 2020, WHO reported >31,000 confirmed human infections, >640 deaths, and declared a Public Health Emergency of International Concern, presumably due to the possibility of a pandemic. The coronavirus 2019 outbreak is the third coronavirus outbreak causing a severe human disease in the past ~20 years. Currently a coronavirus prophylaxis vaccine and therapeutic drugs are not available. In this application we describe the investigation of vaccine candidates. Our team has manufacturing experience expressing a subunit Hepatitis-C virus vaccine candidate and has developed methods for industry-scale vaccine purification using removable purification tags (Logan 2017 Journal of Virology). This work will identify a CoV vaccine candidate that can proceed to the creation of a manufacturing grade mammalian cell line.",2020,2022,University of Alberta,643500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00132,"170710, 175520",Development of a novel DC-targeting vaccine that targets COVID-19 spike protein to control COVID-19 infection [Added supplement: COVID-19 Variant Supplement],"COVID-19 is a coronavirus identified as the cause of an outbreak of respiratory illness that was first detected in Wuhan, China. There is currently no vaccine to prevent COVID-19 infection. The spike protein (SP) of the virus is the key molecule for entry into a cell and is a main target of host protective immune responses. A receptor-binding domain (RBD) located in SP is essential for the infection of COVID-19. Previous studies have demonstrated that RBD of SARS-CoV consists of multiple neutralizing epitopes that induce highly potent neutralizing antibodies. The neutralizing antibody can bind to SARS-CoV and interferes with its ability to infect a cell. These findings suggest that RBD of COVID-19 is an ideal anti-COVID-19 vaccine candidate. Dendritic cells (DCs) are antigen-presenting cells that play critical roles to efficiently present viral antigens to the T cells of the immune system. Therefore, targeting DCs is a promising strategy to improve vaccine effectiveness. Recently, we have developed a highly efficient DC-targeted vaccination technology, and in this study, we will use this vaccination technology to expose the RBD of COVID-19 to host immune system. We will also investigate the potential of this novel vaccine approach to elicit potent immune responses against COVID-19 and SARS-CoV infections in vivo. The success of this proposed study will lay the groundwork for the quick development and production of anti-COVID-19 vaccine candidates, and contribute to a rapid response towards controlling the COVID-19 pandemic in China and worldwide",2020,2022,University of Manitoba,457489.6,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Manitoba,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00133,"170628, 171488, 175558","Shutting down emerging Coronaviruses in humans now and in the future [Added supplement: COVID-19 Variant Supplement, Sex as a biological variable supplement]","In December 2019, a pneumonia associated with the 2019 novel coronavirus SARS-CoV-2 emerged in Wuhan, China. This disease is now named COVID-19. Over 73,000 people have been infected worldwide and over 1,700 people have died from the disease. There is no sign that the rate of new infections and deaths are levelling off or showing signs of declining. Similar coronavirus outbreaks in the future are always a risk and must be addressed now. The goal of this proposal is to establish and test an effective vaccine for SARS-CoV-2. In addition, we will develop a coronavirus vaccine bank containing hundreds to thousands of potential vaccines that can be used at the start of the next coronavirus outbreak. This will give us a head start in trying to treat patients early with the goal of reducing the spread of the disease and subsequent fatalities.",2020,2022,Western University,773688,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00134,"170718, 175559",Mitigation strategies against the public transmission of airborne COVID-19 in high occupancy structures: a program of research to develop optimized mechanical ventilation systems [Added supplement: COVID-19 Variant Supplement],"This research program brings together experts in Engineering and Medical Sciences to develop Non-Pharmaceutical Interventions (NPI) related to mechanical ventilation systems in buildings. These settings have high concentrations of humans in enclosed spaces where the spread of airborne infections can have rapid, extensive, and detrimental consequences in terms of morbidity, mortality, and ultimately productivity and costs. This research program targets a key mechanism of COVID-19 transmission, that is, transport of the virus through heating, ventilation, and air conditioning (HVAC) systems with subsequent inhalation by other people. Currently, it is not clear how human-generated bioaerosols affect airborne virus transmission and how HVAC systems should be optimally designed and operated to reduce the risk of transmission. This research program will include: 1) a thorough review of building science literature related to airborne virus transmission; 2) a policy directive for governing organizations who inform owners and operators of ventilation systems and building code bodies; 3) an inventory and assessment of over 100 buildings with diverse ventilation systems; and 4) an inventory and assessment procedure and protocol for other buildings. This research directly aligns with the objectives of the funding opportunity, in particular, to mitigate the rapid spread of COVID-19 and its potential negative consequences. Based on the research results, we will develop evidence-based guidance and policy recommendations to inform the design/re-design of buildings. This work has the potential for widespread impacts in terms of establishing policy and procedures that can be applied locally, nationally and internationally. Further, this research will inform the immediate response to the COVID-19 outbreak while having a broader impact in terms of the spread of other airborne illnesses/contagions and future outbreaks.",2020,2022,University of Alberta,350300,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C00135,170647,Modelling and Minimising the Impacts of Infection Control Routines on Nurse Workload in Acute Care Under Varying COVID-19 Outbreak Scenarios,"COVID-19 is taking a significant toll on front-line healthcare providers- especially nurses with over 1700 infected and 6 deaths to date. It is no surprise that nurses are questioning the safety of current SARS-CoV-2 infection control routines. These routines also pose extra work in a system where nurses are already working to capacity. If nurses are overworked, then fatigue develops and errors start to occur. Anticipating the demands and required extra personnel for an unknown number of incoming coronavirus patients is difficult. This research team will tackle this problem in two ways. First, we will work with nurses and professionals to refine their infection control routines so as to minimise the workload while simultaneously creating highly reliable safety routines. Secondly, we will develop an approach to creating computer simulations of two emergency departments that allow nurse workload and care delivery times to be precisely quantified. By modelling the care delivery process we are able to see the impact of varying severities of coronavirus outbreaks on the nursing team and, ultimately, how this extra workload affects their ability to deliver the care required to all patients in the unit. This project is a collaboration between researchers at Ryerson University and personnel at the University Health Network. The team will work collaboratively to engage front line personnel in developing the simulation model and co-designing improved infection control routines. The computer models, of two emergency departments with front-line responsibility for coronavirus patient treatment, can be readily adapted to other similar units across Canada. These models provide next-generation decision making support for managers who have to anticipate the unknown impacts of coronavirus, and be prepared to deliver the highest quality of care in ways that are safe for both patients and nurses.",2020,-99,Ryerson University,123033.61,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C00137,170653,Countermeasures to the supply chain disruptions in medical and pharmaceutical industries,"The intended research project focuses on the supply chain disruptions that medical/pharmaceutical industries are currently facing in the Novel Coronavirus Outbreak, due to the suppliers' strategic hoarding and consumers' panic buying behavior under psychological and behavioral uncertainties. Specifically, this proposed research project explores: factors that delay the resilience of medical/pharmaceutical industries' supply chain disruptions caused by the Novel Coronavirus Outbreak; and the feasibility of two countermeasures to the virus outbreak that we propose: (1) establishing a collaborative stock sharing/transshipment system; and (2) making an incentive contract with a potential second source that can produce highly customized medical/pharmaceutical items (e.g., protective clothing for or a new drug for novel viruses).",2020,-99,York University,93035.66,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research","Other secondary impacts | Medicines, vaccines & other technologies", +C00138,170642,"Peer Champion Support for Hospital Healthcare Workers during and after a Novel Coronavirus Outbreak: It's a Marathon, not a Sprint","Experience from the 2003 SARS outbreak taught that hospital workers often experience chronic stress effects for months or years after such an event, including burnout, absenteeism, and interpersonal problems. We learned that supporting healthcare workers requires attention to the marathon of occupational stress, not just the sprint of dramatic stressors that occur while infections are dominating the news. At our hospital, we routinely provide a range of supportive resources for staff, which depend on their needs and often depend on staff actively seeking support. This study's goal is to test if the well-being of hospital workers facing a novel coronavirus outbreak is improved by adding Peer Support Champions: an interdisciplinary team of professionals who actively monitor for early signs of heightened stress within clinical teams, liaise between staff and senior management to improve organizational responsiveness, and provide direct support and teaching (under the supervision of experts in resilience, infection control, and professional education). We will test the effectiveness of Enriched Support by rolling it out to different parts of the hospital in stages, comparing levels of burnout before and after the intervention reaches particular teams and units (this is called a stepped wedge design). By the end of the study, we will have provided Enriched Support to all of our clinical and research staff and many learners (> 6,000 people). We will test the effectiveness of the Peer Support Champions by measuring trends in burnout and other effects of stress over the course of the study in a subgroup of these hospital workers (~1000 people). We have assembled a team of experts in infection prevention and control, healthcare workers' stress and resilience, and continuous professional education. Because occupational stress and burnout are very common in healthcare, we expect this work to produce knowledge that is valuable well beyond the current outbreak.",2020,-99,Sinai Health System (Toronto),355401.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Indirect health impacts | Health service delivery | Health workforce | Individual level capacity strengthening | Institutional level capacity strengthening, +C00139,170635,The role of communication strategies and media discourse in shaping psychological and behavioral response to the COVID-19 outbreak: a comparative analysis between Canada and two Asian countries/regions,"First identified in December 2019 in China, the coronavirus 2019 (COVID-19) has been declared a ""Public Health Emergency of International Concern"" by the World Health Organization (WHO). Large outbreaks can increase the sense of fear and lead to adverse responses from the public, such as denial, rumors, misconceptions, stigmatization, and avoidance behaviors. Both news media and social media play a major role shaping these responses. Little is known about how people of various cultural and social backgrounds react to health information and misinformation. It is also unclear how official information (from the authorities) flows and circulates across levels of governance (from WHO to countries, then from countries to citizens). Our research project aims to contribute to a better understanding of how the health information related to the COVID-19 outbreak is delivered by authorities and media, and how it is received, understood and used by the public. To do so, we will conduct a survey about knowledge, perceptions, and reactions to the COVID-19 outbreak among large and representative samples of the population in three places: Canada, Hong Kong and Philippines. We will also analyze and compare the way information about COVID-19 outbreak is shared in the news media and the social media. Finally, we will look at how health information delivered and received by the population is influenced by the multiple levels of governance. This international research project will allow to 1) evaluate the impacts of communication strategy and misinformation on populations of various backgrounds and 2) draw important lessons that could be applied to future disasters and global threats.",2020,-99,Université de Sherbrooke,356149.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China | Philippines,"Policies for public health, disease control & community resilience",Communication, +C00140,170715,"Assessing and addressing the psychosocial impacts of COVID-19 among pregnant women and health care providers in Anhui, China","On January 31, 2020, the World Health Organization declared the COVID-19 outbreak a public health emergency of international concern. In addition to focusing on immediate clinical/biomedical needs relat-ed to the outbreak, it is also important to consider potential mental health impacts. Pregnancy can be a time of heightened vulnerability, especially during public health emergencies. Women may have several concerns related to: their health and fetus; the health of family, friends, and their infants; access to ser-vices; potential exposure during hospital deliveries; and social isolation, among others. Health care pro-viders (HCPs) also face mental, physical, and social challenges that can affect their wellbeing and ability to care for patients. Building on our team's existing research work and infrastructure, we will first assess the potential impacts of the COVID-19 emergency on pregnant women's mental health (depression) and the implementation of a perinatal depression and screening and management program in Ma'anshan, Chi-na. Secondly, we will then evaluate the effect of a cognitive behavioral therapy intervention aimed at re-ducing depression in pregnant women and investigate changes in the acceptability of and adherence to the intervention. Thirdly, we will investigate potential impacts in terms of adverse birth outcomes (preterm birth, low birth weight, small for gestational age) and explore women's experiences during the outbreak. Fourthly, we also plan to assess anxiety among HCPs and investigate the provision of perinatal health care during and after the emergency. This study aims to contribute to the global COVID-19 response, foster our understanding of the potential mental health impacts of the emergency, reduce public health risk and burden, and help inform clinical and public health responses to the outbreak.",2020,-99,University of Alberta,282433.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00141,170660,"A multi-country comparison of COVID-19 response: Planning, implementation, and health system resilience","The many unknowns of COVID-19 have made the response efforts difficult despite the rapid guidance provided by the WHO. How different countries respond to this pandemic in their preparation and implementation is essential to study and understand. The aim of this project is to compare the public health response to COVID-19 in Brazil, Canada, France, and Mali. Use a case study approach, we will identify strengths and weaknesses in the response, including challenges for health professionals and health systems. To achieve our project aim, we will first document how countries have planned, organized, and implemented public health responses. We will also examine the role of scientific, empirical, and experiential information used in the response planning. We will also study health system vulnerability according to exposure, sensitivity, and adaptive capacities. We will then generate lessons learned for the benefit of public health and health systems and we will organize a workshop between the four countries and international organizations. . Data sources for this study include key stakeholder interviews with decision makers and practitioners, organizational charts providing health human resource data, internal documentation indicating measures taken and dates implemented (e.g., emergency operations center activation, quarantine), and preparedness plans. The research team is composed of international and national experts in epidemic response and health systems analysis from each of the four countries. It is a multidisciplinary team of infectious disease clinicians, social scientists, public health practitioners, epidemiologists, data scientists, and a knowledge transfer expert. Our team includes decision makers and knowledge partners who are key to ensuring our work remains relevant and also provides an important conduit for the uptake of policy and practices recommendations.",2020,-99,Université de Montréal,355646.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe,,,,Canada,Brazil | Canada | France | Mali,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts, +C00142,170651,Assessment of Cancer Patient and Caregiver Perspective on the Novel Coronavirus (COVID-19) and the Impact on Delivery of Cancer Care at an Institution with a Confirmed Case of COVID-19,"Understanding the perspectives that cancer patients and their family members and caregivers have toward the 2019 novel coronavirus (COVID-2019) will be essential to ensure the continuity of their cancer treatments through this infectious outbreak in both the short and long term. A particular dimension that is under-explored and researched is the impact that infectious outbreaks have on the risk perception of cancer patients, including those who are at increased risk of developing infections due to their treatments and immunocompromised state. Furthermore, in the era of continuous and rapid news reporting, social media, and messaging platforms, the proliferation and distribution of COVID-2019 content is unprecedented and further driving distress among this group of patients and caregivers who need to visit medical instituions at regular intervals. At Sunnybrook Health Sciences Center Odette Cancer Center in Toronto, Ontario, we have seen an unprecedented number of clinic appointment cancellations due to fears of being exposed to COVID-2019 given we were the first Canadian institution to confirm a patient infected with COVID-2019. Therefore, to better understand this phenomenon, we have designed a research proposal to address this under explored area in order to develop educational tools to help patients and their families/caregivers make informed decisions based on the true risks during this outbreak with appropriate levels of concern and mitigation. We expect these education interventions to empower patients and families/caregivers on the true risks of COVID-2019 infection and in turn prevent inappropriate clinic cancellations and sub-optimal care for patients undergoing treatment for cancer.",2020,-99,"Sunnybrook Odette Cancer Centre (Toronto, Ontario)",31842.99,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C00143,170716,Organizational response to disease,"Both public and private sector organizations are increasingly faced with the need to deal with disease outbreaks. In particular, organizations are challenged by the need to promote health and health practices among their employees while, at the same time, maintaining their operations. In the current proposal we focus on how employees perceive their employers managing these two goals. In particular we examine how characteristics of the organizational response to disease outbreaks influence employees' own health and health-promoting behaviours.",2020,-99,Saint Mary's University,237433.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Nova Scotia,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00144,170639,Understanding and mitigating real-time differential gendered effects of the COVID-19 outbreak,"Infectious disease outbreaks are considered by policymakers as global, collective problems, assuming a similar impact of pathogens on all people. Yet, the impact of disease on individuals and communities is not homogenous, with women disproportionately affected. The sex and gendered dynamics of the COVID-19 outbreak so far are anecdotal, but the consequences of sidelining these canlimit effective responses in affected regions, as well as prevention and preparedness efforts globally. This project will conduct a gender analysis to identify and document the differential gendered effects of the outbreak and gaps in preparedness and response measures in a dynamic way, providing real time guidance and recommendations to those crafting policy and public health interventions. We will: map and analyze sex disaggregated data on COVID-19 infections and mortality to provide evidence to inform public health responses, decision-making and planning; document and analyze gender impacts of the outbreak in order to strengthen understanding of the impact of COVID-19 on individuals and communities through chatroom and social media analysis and interviews with those infected and affected; conduct gender-based analysis of national and global responses through policy analysis and key informant interviews; produce knowledge translation resources, including a gender matrix and toolkit, to improve policy and public health responses to COVID-19. Findings will contribute to the global response of COVID-19 through strengthening understanding of how individuals and communities understand and react to the disease. The COVID-19 Gender Matrix will be a living, online tool presenting gender analysis questions and data as it is gathered and serving as a template to measure gender indicators, if and where the outbreak may spread. The COVID-19 Gender Toolkit will promote immediate gender mainstreamed actions within policy development, preparedness and response activities.",2020,-99,Simon Fraser University,352284.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Approaches to public health interventions | Policy research and interventions, +C00145,170648,Détermination par la simulation du profil type et des valeurs des professionnels de la santé qui décideront de s'impliquer dans les soins aux patients atteints de COVID-19 ou de s'en retirer.,"The SARS-CoV-2 virus benefits from extensive media coverage in view of the deaths attributable to it. Health centers in Canada are monitoring its evolution and are attentive to the appearance of any new cases. This viral disease can be scary and health professionals may fear for their safety or that of others when working with infected people. This choice to intervene or withdraw from care is generally easy to make in the absence of a real threat and is subject to a rational and conscious process. However, when a person is subjected to a real and imminent threat, they feel stress and fear. This fear, rational or irrational, plays an important role in the decision to intervene or flee. Currently, we do not know how healthcare professionals will respond when faced with an imminent threat such as SARS-CoV-2. We do not know the profile of the people who would agree to intervene, nor that of the people who would prefer to abstain. In this study, we wish to create an authentic simulation environment reproducing an epidemic situation. Participants selected at random (nurses, doctors and attendants) in five health establishments in Canada will be called upon to intervene with people affected by the coronavirus. Through this in situ simulation, we seek to reproduce the mental state in which the health professional will find themselves when intervening with this population. We will thus be able to determine the profile of people ready to intervene, using qualitative and quantitative analysis. Hospitals will be able to use the results to determine the people likely to intervene effectively and efficiently in the event of a major outbreak in order to reduce the organizational and human risks of the epidemic.",2020,-99,Université Laval,153701.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00146,170714,Coronavirus Outbreak: Mapping and Countering Misinformation,"The spread of health misinformation and disinformation are a serious threat to public health, including in the case of the current coronavirus (COVID-19) outbreak. Addressing the spread of COVID-19 misinformation involves identifying the misinformation in circulation, understanding the public impact, and designing and implementing evidence-based solutions to combat the harmful discourse. We propose conducting research into COVID-19 misinformation from multiple angles, developing effective communication and education tools, countering misinformation strategically, and providing policy recommendations to deal with COVID-19 and future outbreaks. Our interdisciplinary team of experts is led by Timothy Caulfield, Canada Research Chair and Health Law Institute Research Director, who has been studying health and science misinformation for over 20 years. Our team will conduct systematic content analyses of traditional and online social media and empirical psychological research on how individuals respond to COVID-19 information. The objective is to assemble and execute a depth-of-analysis sufficient to enact positive outcomes for COVID-19 while establishing a blueprint for future misinformation events. The impact of this course of research will be significant, enabling the development of strategies to combat misinformation, stigma, and fear, to address their underlying drivers, and to improve public awareness, knowledge, and trust. We will meet the call's objectives of contributing to the global response to the COVID-19 outbreak, strengthening the understanding of its public impacts, and providing evidence to inform public health planning, decision making and response. Deploying our expertise and networks will maximize outputs, including to those in health care, government, popular media, and the public at large.",2020,-99,University of Alberta,271917.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00147,170712,Sociocultural and behavioural factors affecting communities' response to countermeasures for COVID-19 epidemic: identifying interventions to build trust,"'Fear might be a bigger threat than the virus.' As public health authorities increase efforts to address the new coronavirus epidemic (COVID-19), rumours, misinformation, and xenophobic online posts are spreading faster than the virus. Fear and misinformation have direct implication on the implementation of effective public health measures to control the epidemic. With this research, we will examine the individual and sociocultural factors that impact individual's and communities' adoption of public health recommendations. This study will use qualitative and quantitative methods to describe online discourses related to COVID-19 in Canada (Tweets and comments on news media report) and to describe individual/ community understanding of disease, priorities, fears, etc. including public health messaging that may impact the acceptance of measures to limit the spread of COVID-19. We will also identify interventions that will help build public trust in authorities responsible for disease spread and management, while dispelling unfounded rumours and xenophobic discourse.",2020,-99,Université Laval,355536.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Nova Scotia,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C00148,170633,La cohésion sociale est-elle possible en situation de crises multiples? L'influence des politiques publiques entourant le coronavirus (2019-nCoV) et les préjugés envers les citoyens et citoyennes d'origine chinoise,"Le monde est actuellement confronte a une situation de crises multiples concernant les prejuges envers la citoyennete d'origines culturelles diverses: les mouvements migratoires, l'omnipresence des medias sociaux et le coronavirus (2019-nCoV). Au Canada, pres de 20% de la population est nee dans un autre pays et 41,8% de ceux-ci font etat de discrimination (Berry & Hou, 2017). Depuis l'eclosion rapide du 2019-nCoV, la communaute internationale observe une hausse des sentiments haineux (Burton, 2020) envers les citoyens et citoyennes d'origine chinoise. Nous soutenons que les politiques publiques vehiculees par les gouvernements ont un impact important sur les attitudes des citoyens et citoyennes a l'egard de la diversite (prejuges), surtout dans un contexte de crises multiples. Dans ce contexte, la collision des menaces a le potentiel de nuire de maniere significative a la cohesion sociale. Ainsi, une serie de questions fondamentales auxquelles il devient urgent de repondre sont soulevees: Est-ce que les politiques publiques des gouvernements influencent reellement le maintien de la cohesion sociale (diminution des stereotypes et de la discrimination)? Est-ce que les medias sociaux et les fausses nouvelles viennent inhiber la transmission efficace des politiques publiques? Comment les messages a la population sur les politiques publiques doivent-ils etre transmis, par qui et de quelle facon? Ce travail de recherche est fait au moyen de plusieurs etudes. Premierement, une etude representative et longitudinale (N=3000) sera menee. Elle permettra d'observer l'evolution des prejuges au fil du temps, conjointement a l'evolution du 2019-nCoV, et aussi la dynamique associee a ce processus. Deuxiemement, une serie de six etudes experimentales sera menee afin de tester l'efficacite des divers messages sur le coronavirus tels que transmis par les agents publics et par les divers medias sociaux tels que Facebook.",2020,-99,Université de Montréal,250234.59,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00149,170626,"COVID-19: The Role of Psychological Factors in the Spreading of Disease, Discrimination, and Distress","The novel corona COVID-19 arose in late 2019 in Wuhan, China, and has rapidly spread from China to other parts of the world. By early February there were over 40,000 confirmed cases in 25 countries, of which 2.5% have been fatal. The WHO declared the virus to be a public health emergency of international concern. COVID-19 is poised to become the next pandemic. For both epidemics and pandemics, psychological factors play a major role in the spread and containment of infection (e.g., non-adherence with hygiene guidelines) and in societally disruptive behaviour (e.g., infection-related discrimination, excessive fear and worry, overuse of healthcare resources); as such, psychological factors have important public health significance. The proposed studies are the first of a planned series of studies with the end goal of developing a rapid assessment system (assessment battery and online delivery platform) that can be used to assess, for any pandemic or major epidemic, infection-related excessive anxiety and xenophobia, and risk factors for these problems. To achieve this end goal, we will conduct three studies with a specific focus on COVID-19 using community samples. The goal of Study 1 will be to develop and validate measures of COVID-19-related anxiety and xenophobia (C-ANX, and C-XEN). In Study 2, these scales will be used to identify the correlates of C-ANX and C-XEN, which can then be used to identify the downstream impacts of these psychological reactions. Based on the findings of Studies 1 and 2, we will develop and evaluate an online public health assessment and information platform (Study 3) designed to reduce the risk of adverse psychological reactions to infectious outbreak. This platform would then be expanded to (a) monitor the psychological impact (as a public health problem) of a pandemic/epidemic, (b) identify people in need of psychological services, and (c) implement interventions for reducing infection-related xenophobia and excessive anxiety.",2020,-99,University of Regina,284734.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00150,170661,COVID-19's Informational Virus: Analyzing the Viral Character and Effects of Social Media Misinformation,"Social media is playing a central yet neglected role in the creation and spread of misinformation about COVID-19 by confusing public understanding, fostering racism and xenophobia, and affecting the capacity of public health officials to communicate scientific facts about COVID-19 to the general public. Without an understanding of the role that contemporary social media plays in the outbreak response, the resultant response may be of limited effectiveness. Thus, this project is based on the following research questions: how is social media-based misinformation shaping both public health and lay responses to COVID-19, and what public health strategies and public policies can be adopted to combat such misinformation and its stigmatizing social impacts? To address these questions, we will develop and apply a cutting-edge mixed-methods approach that combines big data analysis from computational social science with small data analysis from cultural and interpretive sociology. In year one, we will scientifically track misinformation about COVID-19 on Western social media platforms - Facebook, Twitter, YouTube and Reddit - as well as on Chinese social media platforms - WeChat, Weibo, Tencent, and Toutiao. This will be supplemented with interviews with public health officials. In the second year, our analysis will turn towards understanding the effects of social media misinformation about COVID-19, including: xenophobia, racism and stigmatization. We focus on the following lines of investigation: (i) Social Media, Misinformation and Risk Communication in Outbreak Response; (ii) Misinformation in a Post-Truth Environment: Implications for Outbreak Response; (iii) The Role of Misinformation in the Promotion of Stigmatization, Xenophobia and Racism During the Outbreak; (iv) The Relationship of Social Media and Political Culture in Outbreak Response: A Comparison of China and Canada.",2020,-99,York University,219540.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,Digital Health,,,Canada,Canada | China,"Policies for public health, disease control & community resilience",Communication, +C00151,170634,"Combating misinformation, fear and stigma in response to the Covid-19 outbreak: An international collaboration between Canada and Singapore","On January 30, 2020, the World Health Organization declared a pneumonia-like illness (previously 'coronavirus' and now named Covid-19) a public health emergency of international concern. In past months, misinformation about the outbreak rapidly spread, sparking fear and stigmatization of Chinese, Asian and other communities in Canada and abroad. We will conduct this study in partnership with the Chinese Canadian National Council for Social Justice (CCNC-SJ) and the Chinese Canadian National Council Toronto Chapter (CCNCTO), which are advocacy organizations aiming to reduce stigma and racism facing the Chinese-Canadian community. We have also partnered with the Yee Hong Centre in Canada and researchers and government officials in Singapore to explore how cultural and political contexts impact misinformation, stigma and fear. We will conduct a social media analysis to understand Canadian and Singaporean local and federal governments' response to Covid-19 and the public's reaction to these messages. We will conduct multi-language key informant interviews with citizens, health care providers and government officials in Singapore and Canada to identify drivers of misinformation, fear and stigma, and will develop corresponding strategies and tools to mitigate these. We will test our tools with an international, diverse participant panel to ensure our findings are meaningful to a global audience.",2020,-99,Unity Health Toronto,356160.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | Singapore,"Policies for public health, disease control & community resilience",Communication, +C00153,unknown,"Serological studies to quantify SARS-CoV-2 population infection risk in Singapore, Hong Kong and Thailand","We propose a prospective serological study to investigate the incidence of SARS-CoV-2 infection in the general population in three Asian settings: Singapore, Hong Kong and Thailand. The study will aim to measure the age-specific seroprevalence and incidence of SARS-CoV-2 infection at 3 time points, each 6 months apart. Age-specific incidence estimates will be applied to the census population to obtain numbers of infections in the population at each time point. These estimates will be compared with external data on COVID-19 hospitalisations and deaths in each setting, to calculate age-specific infection-hospitalisation and infection-fatality ratios. SARS-CoV-2 antibody kinetics will be defined by studying changes in antibody titres over time. Risk factors for infection will be studied by comparing SARS-CoV-2 seroconverters and non-seroconverters with respect to epidemiological exposures. This study will provide crucial information regarding population exposure and SARS-CoV-2 transmission dynamics, and will provide a complete picture of the relationship between clinically apparent and asymptomatic infections.",2020,2022,National University of Singapore,1043107.65,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Western Pacific,South-East Asia | Western Pacific,,,,Singapore,Singapore | Hong Kong | Thailand,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C00154,unknown,African COVID-19 Preparedness (AFRICO19),"Our project, AFRICO19, will enhance capacity to understand SARS-CoV-2/hCoV-19 infection in three regions of Africa and globally. Building on existing infrastructures and collaborations we will create a network to share knowledge on next generation sequencing (NGS), including Oxford Nanopore Technology (MinION), coronavirus biology and COVID-19 disease control. Our consortium links three African sites combined with genomics and informatics support from the University of Glasgow to achieve the following key goals: 1. Support East and West African capacities for rapid diagnosis and sequencing of SARS-CoV-2 to help with contact tracing and quarantine measures. Novel diagnostic tools optimized for this virus will be deployed. An African COVID-19 case definition will be refined using machine learning for identification of SARS-CoV-2 infections. 2. Surveillance of SARS-CoV-2 will be performed in one cohort at each African site. This will use established cohorts to ensure that sampling begins quickly. A sampling plan optimized to detect initial moderate and severe cases followed by household contact tracing will be employed to obtain both mild to severe COVID-19 cases. 3. Provide improved understanding of SARS-CoV-2 biology/evolution using machine learning and novel bioinformatics analyses. Our results will be shared via a real-time analysis platform using the newly developed CoV-GLUE resource.",2020,2022,MRC/UVRI and LSHTM Uganda Research Unit,2462447.7,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Unspecified,Data Management and Data Sharing,,,Uganda,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2020 +C00155,unknown,COVID-19 Intervention Modelling for East Africa (CIMEA),"COVID-19 is a global threat to health, with many countries reporting extended outbreaks. To date 9 countries in Africa have recorded infection and it seems imminent that East Africa will have introductions and onward transmission. The SARS-CoV-2 virus (the aetiological agent of COVID-19) spreads rapidly (R0~2, serial interval about 1 week), and hence control will be difficult. National plans for dealing with this public health emergency will benefit from predictions of the expected rate, distribution and extent of spread in countries throughout the region, and on the likely impact and feasibility of isolation and contact tracing interventions. We will support the emergency preparations through bespoke modelling, incorporating known demographic population structure, age-related contact patterns and existing mobile phone population movement data. In Uganda and Kenya we will collect epidemiological, genomic and behavioural data through health facility surveillance, household follow-up and contact studies to quantify uncertainties of SARS-CoV-2 virus epidemiology and contact patterns in well and unwell individuals. Results from the study will be rapidly communicated to the relevant authorities, and modelling code and analysis, and data including sequences, placed in the public domain in near real-time. This project could have lasting impact on the role of research in policy decisions.",2020,2022,University of Warwick,1699974.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Uganda | Kenya,Epidemiological studies,Disease transmission dynamics,2020 +C00156,unknown,"The African coaLition for Epidemic Research, Response and Training, Clinical Characterization Protocol (ALERRT CCP)","As part of the response to the emergence of COVID-19, the World Health Organization Africa Regional Office is organizing various Infection Prevention and Control (IPC) and critical care training activities targeted at Low and Middle-Income countries (LMICs) in Africa. While the initiatives taken by WHO/AFRO are critical, training for research into the disease also needs to be targeted at the same LMICs, because being an Emerging Infectious Disease, we need to ""learn-as-we-go"". Clinical research on COVID-19 will have to be closely integrated with the IPC, clinical care, and epidemiological training activities, including use of the WHO First Few X (FFX) Cases and contact investigation protocol for COVID-19. ALERRT proposes to work closely with the WHO/AFRO and Africa CDC and existing networks and structures across Africa and globally to provide the forementioned clinical research training and support. ALERRT is a member of the Global Federation - ISARIC, which has developed a Clinical Characterization protocol for COVID-19. This protocol been endorsed by the WHO and is currently being used in China and across the UK and Europe.Being already established and conducting activities in sub-Sahara Africa, the ALERRT network has the capacity to effectively implement the proposed project.",2020,2022,Kumasi Center for Collaborative Research in Tropical Medicine,1742201.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Unspecified,,,,Ghana,,Clinical characterisation and management | Infection prevention and control,"Supportive care, processes of care and management | IPC in health care settings",2020 +C00157,unknown,"Characterization of SARS-CoV-2 transmission dynamics, clinical features and disease impact in South Africa, a setting with high HIV prevalence","Factors prevalent in Africa such as malnutrition, HIV, tuberculosis and limited access to healthcare, among others, may impact both transmission dynamics and disease progression associated with SARS-CoV-2 infection as well as the burden on the healthcare system and society.We aim to characterize key transmissibility and clinical features of and the antibody response to SARS-CoV-2 as well as to enhance surveillance for COVID-19, identify groups at increased risk of severe illness, estimate the disease burden of medically- and non-medically attended mild, severe-non-fatal and fatal illness and forecast the impact of the outbreak on the healthcare system and the society in South Africa. Particular emphasis will be given to HIV-infected individuals. The aims will be achieved through the implementation of shedding and household transmission studies, collection of sequential serum samples, enhanced facility-based (hospitals and clinics) surveillance among patients with mild and severe respiratory illness in well-established population-based surveillance sites where incidence can be calculated, and healthcare utilization and serological surveys in selected communities. In addition, digital surveillance (based on Google searches) will be used to complement virological surveillance and nowcasting and short-term forecasting (up to 4 weeks) will be implemented over the duration of the epidemic.",2020,2022,National Institute for Communicable Diseases of the National Health Laboratory Service,2484600,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Immunity | Disease transmission dynamics | Disease susceptibility | Disease pathogenesis | Indirect health impacts,2020 +C00158,unknown,Investigation of pre-existing immunity to coronaviruses; implications for immunopathology and pathophysiology of COVID-19 disease,"Background; It is unknown how prior exposure to commonly circulating human coronaviruses (HCoV) impacts immunity against highly-pathogenic species (SARS, SARS-CoV-2 & MERS). There are limited data, across Europe, Asia and Africa, on the prevalence of infection and seroconversion against widely circulating and mildly symptomatic HCoVs (229E, NL63, OC43, and HKU1). There is a current supposition that antibody-dependent-enhancement (ADE) may play a role in the pathophysiology of COVID-19. ADE occurs when non-neutralizing antiviral proteins facilitate virus entry into host cells, leading to increased infectivity in the cells. In such cases, higher viremia has been measured and the clinical course of disease can be more severe. In preclinical animal models, immunopathology was observed after challenge following vaccination with some SARS vaccines. Therefore, concerns have been raised regarding the impact of immunopathology and ADE on prophylactic vaccination against SARS and possibly SARS-CoV-2. Goals: to perform detailed systems serology of pre-existing immunity, in children and adults, from the UK and Africa, towards novel and commonly circulating coronaviruses. Impact: These studies highlight the limited knowledge in the field and a need for a systematic approach to investigate cross-reactive humoral immunity against HCoV to inform the immunopathology and pathophysiology of COVID-19.",2020,2022,University of Oxford,1551892.23,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00159,unknown,A comprehensive study of immunopathogenesis of SARS-CoV-2 infection',"Since December 2019 the emergence of severe acute respiratory infections (COVID-19) in China, caused by the new coronavirus SARS-CoV-2, has posed a huge threat to global health with fatality rates up to 10% in elderly patients. Almost 100% of patients showed bilateral patchy shadows or ground glass opacity in their lungs by chest CT scans indicating acute lung injury (ALI). Therefore, understanding the underlying mechanism(s) of ALI induced by SARS-CoV-2 is very important to inform vaccine safety and immunotherapeutic strategies. In this proposal, we will investigate the host immune responses and their association with severity of ALI in patient samples and animal models. We will bring together a team of experts with complementary expertise including immunopathology in coronavirus infections, up-to-date lab technologies, and know-how to ensure the feasibility of this study with the following goals: 1) defining SARS-CoV-2 specific serum profiles (epitopes) using yeast display antigen library 2) determining antibody functions including antibody-dependent enhancement (ADE) vs neutralizing activities in vitro assays 3) studying T cell (CD4 and CD8) responses to whole SARS-CoV-2 genome 4) evaluating ALI in response to live SARS-CoV-2 infection with or without passive immunity (antibody or T cells) generated from vaccine candidates in a humanized mice model.",2020,2022,Imperial College,1106601.48,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00160,MC_PC_19012,"Centre for Global Infectious Disease Analysis, Imperial College London (GIDA) - COVID-19","This award is being made in recognition that key Centre staff have been redeployed from their usual work, and Centre resources utilised, to contribute to the first phase of a rapid research response to the COVID-19 pandemic. The MRC Centre for Global Infectious Disease Analysis, is at the forefront of delivering timely analysis to inform policy responses to emerging infectious disease threats, and was rapidly awarded an additional £0.5m to support their real-time analysis and modelling of the SARS-CoV2 pandemic and the impact of COVID-19.",2020,2021,Imperial College London,660260,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C00161,MC_PC_19025,ISARIC - Coronavirus Clinical Characterisation Consortium (ISARIC-4C),"This award is being made in support of urgent research costs to enable sampling amongst UK COVID-19 cases. This is essential in developing diagnostics, therapeutics (monoclonal antibodies) and understanding the pathogen and the natural history of the disease, as well as developing rapid prognostic tools. This funding support will ensure samples are distributed safely to researchers. Research could change the course of the rapidly spreading outbreak.",2020,2021,University of Edinburgh,98958.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies",2020 +C00162,MC_PC_19026,MRC Centre for Virus Research (MRC CVR) - COVID-19,"This award is being made in recognition that key Centre staff have been redeployed from their usual work, and Centre resources utilised, to contribute to the first phase of a rapid research response to the COVID-19 pandemic. The MRC Centre for Virus Research at the University of Glasgow (CVR) represents the UK's largest grouping of human and veterinary virologists. The Centre has contributed expertise to recent Ebola outbreaks, and is now working on SARS-CoV2 with £0.5m of supplementary funding. Working in collaboration with the NHS Greater Glasgow & Clyde West of Scotland Specialist Virology Centre, CVR researchers completed the genomic sequencing and analysis of Scotland's first confirmed Covid-19 case within 48 hours of diagnosis.",2020,2020,MRC - University of Glasgow Centre for Virus Research (CVR),660260,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C00163,MC_PC_19055,nCoV: Rapid Clinical Development of ChAdOx1 nCoV-19,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. ChAdOx1 is a replication-deficient simian adenoviral vector that provides a platform technology for the production of vaccines against many infectious diseases. For Middle East Respiratory Syndrome (MERS) coronavirus, a single dose of the ChAdOx1-vectored MERS vaccine resulted in protection against MERS challenge in non-human primates and the induction of strong humoral and T cell responses in a Phase I clinical trial. The same vaccine design has now been followed to produce ChAdOx1 nCoV. Preclinical studies of the vaccine will be initiated by the end of February. This will include demonstration of vaccine immunogenicity (antibody and T cell) in mice, followed by vaccine immunogenicity and efficacy against nCoV-19 challenge in ferrets and non-human primates with collaborators at PHE Porton Down and NIH. A pre-GMP vaccine seed stock is in production at Oxford's GMP manufacturing facility, and will be provided to Advent, Italy, which will produce the first 1000 doses for clinical studies. In parallel with preclinical studies and vaccine manufacturing, Oxford will work with the MHRA on a rapid release testing package. This will employ deep sequencing of the Cell Harvest and Drug Substance to identify any potential replication competent adenovirus and adventitious agents rather than following the existing set of in vivo and in vitro assays, greatly reducing the time to cGMP certification. A phase I/II clinical trial will then be undertaken to demonstrate vaccine safety and immunogenicity in adults, older adults and children.",2020,2021,University of Oxford,2788155.14,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom | Italy,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00164,MC_PC_19056,"COVID-19: multi-arm, multi stage adaptive clinical trial (CoV-MAMS)","This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Medicines to prevent and effectively treat 2019 coronavirus disease (COVID-19), especially severe lower respiratory tract (LRT) illness, would save lives and reduce healthcare pressures. Randomised controlled trials (RCTs) are ongoing in China of lopinavir/ritonavir [ChiCTR2000029308] and remdesivir [NCT04257656 and NCT04252664]. Additional potential therapeutics are being considered by the WHO. Building on our existing experience and capabilities, we are proposing to implement a multi-arm, multi-stage (MAMS) RCT. This trial will be designed to evaluate up to four experimental therapeutics in a flexible, adaptive framework. MAMS designs have been shown to be more efficient than sequential RCTs or factorial designs. The trial will enrol patients hospitalised with laboratory confirmed COVID-19. Patients will initially be randomised equally to receive one of up to 4 active treatments or control. Should not all active arms be available at study onset, patients will be randomized between available active arms and control. The trial will commence with two active arms, lopinavir/ritonavir and low dose dexamethasone. Additional active arms will be added as data and drug availability allow.",2020,2021,University of Oxford,2699935.59,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III | Randomized Controlled Trial",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Western Pacific,,,,China,China,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C00165,MC_PC_19057,Repurposing FDA-Approved Drugs for Treatment of 2019-nCoV-induced Disease,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. A novel coronavirus (SARS-CoV-2) originating in Wuhan, China has reached pandemic status and causes a disease termed COVID-19. Therapeutics and vaccines are urgently needed. The normal pace of new drug development is incompatible with strategies to rapidly combat COVID-19. Drug combinations with antiviral and anti-inflammatory activity will likely be essential to treat infected patients, as acute respiratory virus-induced disease is commonly mediated by inflammatory responses to infection. An alternative strategy to rapidly identify therapeutics to combat SARS-CoV-2 is drug repurposing. As the drugs are already FDA-approved, it is cost-effective and time-efficient. To this end, we will exploit MuSIC (multiplex screening of interacting compounds) screening of a unique library consisting of ~1,000 drugs to identify single and synergistic interacting compounds that have either SARS-CoV-2 antiviral activity or anti-inflammatory activities, with limited/no toxicities. This library includes FDA-approved compounds and antiviral drugs that showed activity against other cornoviruses (SARS-CoV & MERS-CoV) (1). Drug candidates will be validated using SARS-CoV-2-infection of well-differentiated primary human airway epithelial cell cultures (WD-PAECs), which are excellent surrogates of human airway epithelium. WD-PAECs represent the most relevant pre-clinical translational model for screening therapeutic drugs for COVID-19. SARS-CoV-2 uses that same receptor/entry factors as SARS-CoV (2), which infects WD-PAEC cultures. Our findings will identify candidate drugs for treating COVID-19 patients, which can quickly enter clinical trials or be employed for compassionate use, especially in the case of viral diseases lacking specific treatments. (1): Mani et al. J Young Pharm, 2019; 11(2) : 117-121 (2): Hoffmann et al. bioRxiv https:",2020,2021,Queen's University of Belfast,378991.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00166,MC_PC_19058,Rapid development of manufacturing processes for future production of adenovirus-vectored COVID19 vaccine at million-dose scale,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. We aim to provide, in <6 months and probably c. 4 months -A GMP process to produce the University of Oxford's (UOXF's) simian adenovirus-vectored COVID-19 vaccine at 200L/ c. 1m-dose scale -With MHRA engagement, a contingency plan (subject to funding) to make available 1m doses of GMP-like UK-cleanroom-produced material for clinical use as soon as possible. -Development of options for 1000L-scale (>5m dose) manufacturing in UK & abroad. Small-batch GMP and clinical trials of the UOXF vaccine are already planned. Supported by the extensive human safety/ immunogenicity record of these vectors, and anticipating supportive primate efficacy/ immunopathology safety data in April, we are contingency planning an emergency clinical trial programme. With a £0.25m in-kind contribution from PallBiotech, including access to a fully-equipped process development (PD) facility, and starting from our existing GMP 3L-scale process, we are already performing scale-up preparation experiments and anticipate a 50L run at Pall's facility and then 200L runs as needed, within funds requested here. With Co-I J Humphreys (VMIC), we are contingency planning near-immediate access to 200L-capable cleanrooms at two CDMOs, both partners in this application (Cobra in Keele, UK & Halix in Leiden NL). We have requested an emergency meeting with MHRA to discuss regulatory mechanisms to make vaccine available for large-scael use as soon as possible.",2020,2020,University of Oxford,527399.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2020 +C00167,MC_PC_19059,ISARIC - Coronavirus Clinical Characterisation Consortium (ISARIC-4C),"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. It seems highly likely that SARS-CoV-2 will cause disease and mortality unprecedented in modern times. Despite rapid publication of data from China, many unanswered questions remain that have immediate bearing on control and treatment of COVID-19: • Pathogen: how does transmission occur and over what period? What features of the virus drive transmission and severity? • Host: How can diagnosis be improved? How can severity be predicted? Does prior immunity to other viruses worsen disease severity? How does (non)pulmonary organ injury occur? Can therapy be tailored according to disease mechanisms? Which bacterial or fungal co-infections contribute to critical illness? This is a new disease. There is a high chance that clinical trials will fail to detect therapeutic effects, by enrolling at the wrong time, or missing key subgroups or endpoints. Deep biological phenotyping can mitigate these risks, providing rapid, efficient clinical evidence. Our response has been planned and tested over the past 8 years within the International Severe Acute Respiratory Infection Consortium (ISARIC). We will recruit at least the first 1300 consenting UK patients, and 1000 suspected cases, as the base of a coordinated national response, using our established, internationally-harmonized protocol (ISARIC Clinical Characterisation Protocol) to: • Provide a unified foundation for clinical trials, enriching design and interpretation • Provide an open-access platform for evaluation of diagnostics and therapeutics • Establish a sample repository with independently-managed availability to researchers and to industry. • Use real-time data to inform the response by funders, public health and hospitals ISARIC-4C is a consortium of experts with a proven track record of high-quality outbreak research. We have already recruited 87% of cases reported in the UK.",2020,2022,University of Edinburgh,6293268.77,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis",2020 +C00168,MC_PC_19060,nCoV: Developing CoV-bnMABs for therapy of highly pathogenic coronaviruses including SARS-CoV-2,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Recently we have investigated antibody cross-reactivity between SARS-CoV and MERSCoV using a cohort (n=128) of SARS convalescent samples (serum and PBMC) collected during the 2003 outbreak in China. We isolated: • A panel of human mAbs (hmAbs) (n=12) specific to the cross-reactive epitopes between SARS-CoV and MERS-CoV by yeast-surface-display technology from PBMCs of SARS patients (Fig.1A) • Four of 12 hmAbs showing stronger neutralizing activities against both SARS- and MERS-CoVs in pseudotype (Fig.1B) or wild-type virus assays (Fig.1C), namely the CoV broadly neutralizing mAbs (CoV-bnMABs). Because a new highly pathogenic coronavirus (2019-nCoV renamed as SARS-CoV-2 by WHO on 11th Feb) outbreak occurred in December 2019 in China, we compared CoV sequences and alignments and found that the S protein (the major target of antibody response) of 2019-nCoV shares higher homology with SARS-CoV (77 %) as compared with MERS-CoV (35%). Thus, we hypothesize that some of CoV-bnMABs generated from SARS patients will cross react with SARS-CoV-2 in addition to MERS-CoV and SARSCoV. Indeed, our preliminary data (obtained on 9th Feb 2020) have shown that the CoVbnMABs can specifically bind to SARS-CoV-2 S protein expressed on the surface of 293T cells (Fig.2). Therefore, we propose here to further characterize the CoV-bnMABs in terms of protective efficacy against SARS-CoV-2 while scaling up antibody production for IND-enabling CoVbnMAB CMC development, aiming to rapidly develop therapeutic antibodies for the current outbreak. Technically, in collaboration with a team of experts from UK and China, we will accomplish essential pre-clinical studies within 12 months and prepare for clinical trials.",2020,2021,Imperial College London,787694.13,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | China,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C00169,MC_PC_19063,A protease activity profiling strategy to inhibit cell-to-cell transmission of SARS-CoV-2,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. This proposal focuses on the molecular underpinning of enhanced transmissibility of SARS-CoV-2, and develop strategies to attenuate it to arrest viral spread. Viral infections spread based on their ability to overcome multiple barriers and move from cell to cell, tissue to tissue, person to person and even across species. Host expansion, transmissibility and tissue tropism of coronaviruses are primarily determined by host adaptations of the viral Spike. Alignment with related coronaviruses has revealed that SARS-CoV-2 Spike carries additional protease-cleavage sites. However, whether the SARS-CoV-2 Spike undergoes additional processing, the identity of cellular proteases involved and whether they confer enhanced transmissibility to SARS-CoV-2 is currently not known. To arrest the chain of transmission, we will determine: (i) the identity of the cellular proteases, (ii) whether inhibiting the proteases blocks virus transmission, (iii) whether blocking cleavage of the viral Spike itself blocks transmission. Using activity-based protein profiling we have captured serine-proteases that are specifically activated in SARS-CoV-2 infected samples but not in SARS- or MERS-CoV. We have already identified two such proteases and will scale-up to identify the others. We aim to inhibit these proteases both genetically and pharmacologically, to test functional consequences on virus transmission and tissue tropism. Additionally, we aim to mutate the proteolytic processing sites on the viral Spike itself, to assess effects on tissue tropism and transmission. Our unique combination of tools and expertise, puts us in an excellent position to study and inhibit transmission of SARS-CoV-2.",2020,2021,University of Oxford,263650.47,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C00170,MC_PC_19064,Understanding environmental and airborne routes of transmission,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. This project is intended to provide the evidence base for environmental infection control to help control transmission in the healthcare and other environments. The following questions will be addressed Does SARS-CoV-2 survive in the aerosol state in a range of environmental conditions and for how long? Can SARS-CoV-2 survive on a range of environmental surfaces found in healthcare facilities and domestic premises and for how long? Are commonly used room decontamination systems effective at inactivating SARS-CoV-2? Are commonly used air sampling techniques capable of effectively sampling SARS-CoV-2 for subsequent analysis by PCR and plaque assay? All these questions will be addressed using fully developed published methodologies currently available at PHE Porton Down allowing the questions to be answered rapidly. The results of the studies will inform infection control practices and other linked studies carried out within healthcare facilities within the UK and internationally.",2020,2021,Department of Health and Social Care,375404.76,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2020 +C00171,MC_PC_19065,Understanding the dynamics and drivers of the COVID-2019 epidemic using real-time outbreak analytics,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Efficient response to COVID-19 requires an understanding of the epidemiological and behavioural drivers of disease transmission. Due to the rapidly evolving outbreak and the mitigation strategies likely to be put in place at different times, analyses of epidemic drivers and policy evaluation need constant updating to provide relevant data-driven evidence to inform evolving public health choices. We will provide rapid, continually updated estimates of key epidemiological features such as disease severity and transmissibility measures and lengths of stay. Surveillance, serological and sequence data (where available) will be analysed accounting for censoring and reporting delays. Mathematical models will be fit to the emerging data streams using Bayesian methods to provide regular forecasting updates and assess the impact of current or potential future interventions. Contact and precautionary behaviours will be monitored in a representative cohort along with information on risk awareness and perceived efficacy of interventions to refine transmission models, improve forecasting, and assess the effectiveness of social distancing measures. Special attention will be given to sharing results in an open and timely manner. Epidemiological parameter estimates and forecasts will be shared on a public website, updated daily. User-friendly web interfaces will allow users to generate model outputs and investigate the impact of specific model assumptions on different policy findings. Highlights of essential results will be gathered in short policy briefs updated weekly. Findings will immediately inform UK policy through participation on UK Government advisory committees.",2020,2021,London School of Hygiene & Tropical Medicine,1262687.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures,2020 +C00172,MC_PC_19066,"A global registry of women affected by COVID-19 in pregnancy, understanding natural history to guide treatment and prevention","This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. BACKGROUND. In the current COVID outbreak, there are case reports with variable outcomes reported for 18 women affected by nCoV in the third trimester, 50% delivered pre-term but there were no reports of vertical transmission. Therefore there are significant knowledgegaps regarding the impact of COVID-19 on mothers' and babies' health at all stages of pregnancy, including delivery and neonatal care, due to lack of primary data. SARS and MERS resulted in >25% case fatality in pregnant women, with worse effects in those infected in earlier pregnancy. AIMS To understand the natural history of COVID-19 in pregnancy, in order to guide treament and prevention during the outbreak. DELIVERABLES Registry: We will construct a registry of women affected by COVID-19 during pregnancy, detailing presenting symptoms, clinical course, key diagnostic testing modalities and pathology results, adverse pregnancy outcomes, including vertical transmission, perinatal and neonatal outcomes. Pseudonymised data will be entered by health professionals via a password-protected web portal; the database will be hosted in an established clinical trials unitwith a study co-ordinator, senior data manager and statistician. We have a network of collaborators across Europe, China and USA to identify cases from these areas. Our senior project-partners in China and Hong Kong have expertise in women and children's health and epidemiology and will facilitate case reporting in areas which have a high prevalence of COVID-19 . This registry will be used to produce weekly online reports of aggregated, anonymised data during the outbreak to inform treatment and prevention during the outbreak, within the period of the grant. Data sharing (for pseudonymised individual participant data) will be made available for ethically approved research during and after the outbreak.",2020,2021,Imperial College London,313278.91,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month) | Unspecified,Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Western Pacific,,,,United Kingdom,China | Hong Kong | United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C00173,MC_PC_19067,Spatial heterogeneity in transmission and the impact of interventions: a mathematical modelling approach,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Predicting the size and duration of potential COVID-19 outbreaks is an essential component of public-health planning and preparedness. Mathematical models of disease transmission are potentially powerful tools for predicting the course of an upcoming epidemic and evaluating control and mitigation strategies. However, standard models of disease transmission without population structure overestimate the speed of invasion of a novel pathogen. We have developed a spatial metapopulation transmission model for the UK that is grounded in demographic data which incorporates regular (commuter-like) movements of individuals. In previous work, we demonstrated that regular, repeated movements lead to slower epidemic spread. Adapting this model for COVID-19, we estimated that an uncontrolled epidemic in England and Wales would peak ~4 months following sustained person-to-person transmission, but that seasonality in transmission could substantially alter the timing and magnitude of the peak burden. Here, we propose to use this model to evaluate control and mitigation strategies for COVID-19. Guided by the World Health Organization-identified research priorities and PHE needs, we will estimate the impact of travel restrictions, border screening and quarantine policies. We will also assess the effects of social distancing measures and other non-pharmaceutical interventions on peak burden and epidemic timing and rank measures by effectiveness. The model will also be adapted to assess and rank pharmaceutical deployment strategies. Our vision is to make the model adaptable and available to other countries and settings, both with and without census and commuting data. Key challenges include modelling commuting patterns, incorporating realistic age structure, adding an observation model to capture morbidity and mortality and including behaviour change which could substantially alter dynamics.",2020,2021,University of Exeter,72718.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C00174,MC_PC_19068,"Rapid co-design, implementation and evaluation of a digital behaviour change intervention to improve hand hygiene and limit spread of the COVID-19 outbreak","This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. This project will evaluate how an existing digital public health intervention can be very rapidly adapted and optimised for the changing needs of an infection outbreak, using novel participatory-co-design methods, and building on partnerships with PHE and leading Chinese researchers. We will translate and immediately widely disseminate in both UK and China our NICE-endorsed 'Germ-Defence' digital infection control intervention for the general public. We will then engage with stakeholder (n=15) and PPI (n=20-30) online panels in each country to co-design, update and optimise the intervention as required for re-release in later and second phases of the outbreak. At every stage of dissemination we will document reach and impact using unobtrusive measures of usage and handwashing intentions and behaviour. We will triangulate these data with findings from online interviews with a purposive user sample (n=20-30) in each country to understand contextual effects on engagement. We will also carry out a rapid online trial in China (n = 1318) comparing the effects of the initial and adapted versions of the intervention on infection control beliefs, attitudes and behaviour, to evaluate the value of the adaptation process. This work is intended to contribute directly to the management of the outbreak by preventing infection transmission and slowing the spread of infection, so that the healthcare system will have more capacity to cope with demand. This work will also contribute to a better understanding of how to rapidly optimise public health interventions for future emergencies, and the factors influencing behaviour relevant to infection transmission.",2020,2021,University of Southampton,308082.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,Digital Health,,,United Kingdom,United Kingdom | China,"Infection prevention and control | Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C00175,MC_PC_19069,nCoV: Understanding the dynamics of policy development and healthcare worker behaviour in the UK during the Covid-19 public health emergency,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. During public health emergencies policymakers are under incredible pressures from many sides, including the media, public, healthcare workers, and politicians. The decisions made have wide impacts on many sectors of society, especially healthcare workers at the front line of the outbreak response. This proposal responds to the theme of ""understanding and influencing behaviour of institutions and individuals."" We aim to understand better how UK policymakers arrive at decisions during the Covid-19 outbreak, and the impact of those decisions on UK healthcare workers. Making sense of policy decisions usually occurs after an outbreak, and thus can only impact on future events. Here we propose a novel prospective evaluation, monitoring conventional and social media data, and gathering information from key policy stakeholders (e.g. Jeremy Farrar and David Heymann) about their activities, and the drivers of policy choices (Work Package 1). In parallel we will purposively select key informants from primary care and hospital settings to gain insight into healthworker concerns and perceptions regarding the response to Covid-19, including views on service level adaptations following policy changes (Work Package 2). This work requires rapid activation to capture timely, valid information about attitudes during the outbreak, and deliver prompt results to policymakers. We are already piloting the research, with pump-prime funding from the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, and will scale it with MRC support. Our team has extensive experience evaluating the impacts of policy in healthcare systems in the UK and internationally, leading to change in practice.",2020,2021,University of Liverpool,364281.66,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2020 +C00176,MC_PC_19070,"Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour.","This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 is set to become a global pandemic. Near real time information is needed to inform NHS planning and public health response. This includes community incidence (regardless of seeking care), risk factors for disease, clinical symptoms, case hospitalisation and mortality ratios, asymptomatic viral shedding, asymptomatic infection, household transmission risk and population behaviours during periods of wellness and illness (including social contact and movement, respiratory hygiene and health seeking behaviours). This information can only be gathered accurately through large scale community studies. Our experience of the MRC/Wellcome FluWatch study and ESRC BugWatch study allows us to rapidly establish two six-month national household cohorts (April-September 2020) and (October 2020-March 2021) of 25,000 individuals each (2,500 in each region of England and Wales) for online symptom and behaviour reporting and optional use of an app allowing their mobile phones to be used as GPS trackers enabling secure transfer and analysis of detailed movement patterns. Two sub-cohorts (10,000 individuals each) will also self-swab when ill for detection of COVID-19 and other circulating viruses. We will also conduct a London based study (200 households) following household contacts of COVID-19 cases for 28 days with daily symptom reporting, regular swabbing and baseline and follow up serology to investigate household transmission and asymptomatic infection and virus shedding. We will use data from Virus Watch to train whole population prediction models based on social media and search engine data and develop spatiotemporal models. Findings will be rapidly disseminated via online dashboards informing the public and decision makers.",2020,2022,University College London,4443942.29,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +C00177,MC_PC_19071,A mixed-methods evaluation of advice on isolation and health-seeking to contain transmission,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Measures to contain and delay COVID-19 in the UK include supported isolation for repatriated individuals, targeted advice to self-isolate for confirmed cases, contacts and symptomatic people, ""shielding"" for extremely vulnerable people and social distancing for the rest of the population. Evidence suggests that advice to self-isolate is not always adhered to and experiencing supported or self-isolation can have detrimental effects on mental health and wellbeing. We aim to assess the effectiveness, acceptability and impact of isolation and distancing interventions to strengthen the current management of COVID-19. We propose to implement a series of mixed-methods evaluations, focusing on supported and self-isolation and social distancing. This includes a rapid evaluation of supported isolation to assess adherence to advice and impact on mental health and wellbeing, using quantitative surveys and semi-structured interviews. We will also evaluate self-isolation and social distancing advice during the containment and delay phases, using a quantitative survey and follow-up interviews with people identified through contact tracing activities, extremely vulnerable ""shielded"" individuals and the general population, to determine barriers and facilitators to adherence and assess the impact of advice on health and wellbeing, including identifying any differences between the different groups. Finally, an ethnographic study will focus on community responses in the UK and China through a series of narrative interviews and analysis of documentary sources. We will produce interim and final reports, focusing on policy and practice implications for management of supported isolation facilities, communicating advice to self-isolate and socially distance and the development of a communications strategy.",2020,2021,Department of Health and Social Care,511398.07,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | China,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication | Policy research and interventions,2020 +C00178,MC_PC_19074,Estimating severity from multiple data sources using Bayesian evidence synthesis,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. In preparing for a possible COVID-19 pandemic, estimates of severity, in particular of both the numbers of infections occurring at different levels of severity and the infection- and case-severity risks, are crucial to understand and predict the burden and impact of the epidemic on healthcare services. Such estimates are most importantly needed by age and risk group (e.g. defined by co-morbidities) strata, although in the early stages of an epidemic, strata-specific information is rarely available. No single dataset can provide enough information on its own to estimate severity, but estimation is feasible by synthesising multiple datasets, such as: line-listing data from first few hundred type studies; surveillance data including case counts, numbers accessing healthcare, and numbers of deaths; cohort studies; and household studies. Such a synthesis needs to account for biases inherent in each data source, including differential ascertainment by severity level; and to account for the incomplete nature of the data, which, collected in real time, are typically affected by censoring of final outcomes (recovery/hospital discharge or death). We propose to make the best use of both individual- and aggregate-level data that will become available, by using a combination of survival analysis techniques (e.g. curerate mixture or competing risks models) and Bayesian evidence synthesis in a single analysis to estimate severity in real time, as data accumulate over the course of the epidemic, and once the epidemic is over.",2020,2022,University of Cambridge,223400.96,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility,2020 +C00179,MC_PC_19075,Early Assessment of COVID-19 epidemiology and Vaccine/anti-viral Effectiveness (EAVE II),"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. EAVE (Early Estimation of vaccine and Anti-Viral Effectiveness) was a NIHR-funded project on pandemic influenza, which created a Scotland-wide cohort of 227,000 individuals recruited from 40 general practices together with stored serology samples from 1,000 individuals. EAVE established a national electronic cohort though linking health data sets from general practice, prescribing, hospitalisations and virology testing using the unique Community Health Identification (CHI) number for residents of Scotland. We plan to repurpose and expand this cohort to collect electronic data from 1.2m individuals living in Scotland to study COVID-19. We will augment the cohort by collecting and storing residual sera samples and by sequencing virus from patient specimens. Both of these, are being taken as part of routine care from a sample of these individuals. We will track the progress of the COVID-19 epidemic in near real-time using the EAVE II cohort. We will be able to model the full course of the epidemic from genome sequence data. Once a serological test becomes available we will be able to refine this model and provide precise estimates of the attack rates in different sub-populations, and accompanying hospitalisation and fatality rates. EAVE II will help to identify the clinical features of the epidemic and, in due course, provide estimates of the effectiveness of any vaccines and anti-viral therapies deployed. Ethical and Privacy Committee approval has previously been given for the EAVE study and we anticipate the same approvals will readily be obtained for this follow-on study.",2020,2022,University of Edinburgh,698668.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis",2020 +C00180,MC_PC_19081,Coronavirus STORY (Serum Testing of Representative Youngsters),"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. This COVID-19 paediatric sero-epidemiology study will adapt an existing national researchnetwork and ethically-approved NIHR-funded study to collect sufficient childhood andteenage serum samples for near real-time monitoring of increases in paediatric COVID-19sero-positivity rates across the UK in 2020.The importance of sero-epidemiological monitoring is emphasised in the Public HealthEngland (PHE) pandemic influenza protocol, currently being adapted in response to theCOVID-19 threat. This requires the monthly collection of 1000 serum samples, including100 per month in each of the 0-4, 5-9, 10-14 and 15-19 year old age-groups. This isessential to understanding the rates of symptomatic and asymptomatic infection inchildren, a population that are the predominant transmitters of most respiratory viruses.This information is in turn crucial to understanding the severity of COVID-19 disease inchildren, as well as modelling the spread of this virus through the community and planningan effective public health response.The challenge of obtaining blood samples from representative cohorts of children (ratherthan residual sera from sampling for clinical purposes) had already led to the OxfordVaccine Group (OVG), PHE and seven regional partners throughout England establishingthe 'What's the STORY (Serum Testing of Representative Youngsters)' network toevaluate antibody levels against vaccine-preventable diseases. This study hascommenced, and with additional funding would be expanded to collect 3200 samplesthroughout 2020, including collection of individual level information on recent respiratoryillnesses and relevant medical history. Further extension would be possible if needed withappropriate resourcing. This study will form a rapid, responsive and crucial component ofthe UK response to this emerging global threat.",2020,2021,University of Oxford,708887.59,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C00181,unknown,Epidemiological modelling to support the global COVID-19 response: how to mitigate impact in low-income and crisis-affected settings,"The current COVID-19 pandemic is the greatest threat posed by a respiratory virus since the 1918 H1N1 influenza pandemic. To date, the majority of epidemiological modelling analyses have focused on high-income countries. However, there is an equivalent need for models appropriate to low- and middle-income countries (LMICs) that comprise 85% of the world's population and have differing demographics and behaviours that are not captured by existing models. To address this, we will use a model of SARS-CoV-2 transmission to forecast epidemics and healthcare needs in LMICs, explore the potential impact of proposed interventions, and estimate their impact in real-time. The model will fit to individual country surveillance data to support estimation of the reproduction number, and projections will be made of the potential impact of alternative mitigation and suppression strategies, including household quarantine and social distancing, both generally and in vulnerable populations. The fit of the model to COVID-19 case count and mortality data collected after the implementation of various interventions will be used in real-time to evaluate their effectiveness in individual LMIC countries and the criteria for lifting social distancing measures explored using the best fit model.",2020,2020,N/A,123923.25,Other,Not applicable,Not Applicable,Unspecified,Vulnerable populations unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,,Europe,,,,,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C00182,unknown,Managing COVID-19 epidemics in low- to middle-income and crisis-affected settings: epidemiological and economic evaluation,"The COVID-19 pandemic is rapidly escalating and poses a potentially catastrophic threat to low- and middle-income countries (LMICs), as well as crisis-affected populations. To support evidence-based, real-time decision-making by countries, donors, humanitarian actors and other stakeholders, we propose a six-month multi-disciplinary project built around three workstreams: evaluation of the health, fiscal and macro-economic impact of response options; global analysis; and technical support for decision-makers and local researchers. Specific activities (and associated deliverables) include the following:improve global data collation and capacity for economic analysis around COVID-19evaluate the health and economic implications of COVID-19 response options using micro-economic modelsquantify the macro-economic consequences of COVID-19 response optionspredict the transmission and mortality of alternative shielding options for high-risk populationsprovide a regular series of global COVID-19 health impact, resource needs and cost estimatesadvise LMIC governments, donors and humanitarian actors on COVID-19 strategysupport technical guidance and coordination for humanitarian actorssupport LMIC economists to provide local evidence on COVID-19 responses.",2020,2021,N/A,236070.04,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,,Europe,,,,,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Policy research and interventions | Economic impacts,2020 +C00183,unknown,Malawi-Liverpool-Wellcome Trust COVID-19 Epidemic Preparedness,"Malawi is at high risk of COVID-19 epidemic spread, the healthcare system is fragile and the population vulnerable to severe disease. We propose epidemic preparedness activities for COVID-19. These are split into three work packages: diagnostic capacity and genomics surveillance; secondary care; and epidemiology and control. Strategically, we have designed our activities to develop a platform for Malawi-Liverpool-Wellcome Trust (MLW) to rapidly pivot into response mode to support the healthcare system and deliver excellent research for current and future epidemic disease threats. Our key goals are to provide diagnostic capability in Malawi for the COVID-19 epidemic, and to develop clinical and epidemiological tools to manage epidemic disease in Malawi",2020,2021,N/A,320405.13,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,,Africa | Europe,,,,,United Kingdom | Malawi,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen genomics, mutations and adaptations | Impact/ effectiveness of control measures | Supportive care, processes of care and management",2020 +C00184,unknown,"Clinical Terapheutical Trial (TT): hidroxicloroquina, azitromicina y tocilizumab","Clinical Terapheutical Trial (TT): hidroxicloroquina, azitromicina y tocilizumab",2020,-99,Instituto de Investigación Sanitaria del hospital de la Santa Creu i Sant Pau de Barcelona,871948.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C00185,unknown,Plasma with antibodies from already cured patients,Plasma with antibodies from already cured patients TT: plasma con anticuerpos de pacientes ya curados,2020,-99,Instituto de Investigación Sanitaria Puerta de Hierro de Majadahonda,691501.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C00186,unknown,"TT: Comparing efficacy between hidroxicloroquina, lopinavir-ritonavir y combination of hidroxicloroquina y azitromicina","TT: Comparing efficacy between hidroxicloroquina, lopinavir-ritonavir y combination of hidroxicloroquina y azitromicina",2020,-99,Instituto de Investigación Sanitaria del Hospital La Paz de Madrid (IdiPaz),512136,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C00187,unknown,"TT Comparing efficacy between remdesevir, ritonavir/lopinavir, hidroxicloroquina e interferón beta.","TT Comparing efficacy between remdesevir, ritonavir/lopinavir, hidroxicloroquina e interferón beta.",2020,-99,Instituto de Investigación Sanitaria del Hospital Clínico de Madrid,240840,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C00188,unknown,Preventive Trial (PT): quimiopreventivo weekly doses of oral mefloquina,Preventive Trial (PT): quimiopreventivo weekly doses of oral mefloquina,2020,-99,Hospital Universitario de Elche,52488,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C00189,unknown,PT Defibrotide ( anticoagulante) to prevent Lung SDS,PT Defibrotide ( anticoagulante) to prevent Lung SDS,2020,-99,Instituto Murciano de Investigaciones Biomédicas (IMIB),124200,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C00190,unknown,TT: Sevoflurano as anesthesia for patient who need intubation.,TT: Sevoflurano as anesthesia for patient who need intubation.,2020,-99,"Instituto de Investigación Sanitaria del Hospital Clínico de Valencia (INCLIVA),",23220,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C00191,unknown,PCR: Quick diagnostic test based on nanotecnología techniques,PCR: Quick diagnostic test based on nanotecnología techniques,2020,-99,Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-Nanociencia).,367200,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00192,unknown,Preclinical Research (PR): SARS-COV2 proteins into microspheres to upgrade immune respond,Preclinical Research (PR): SARS-COV2 proteins into microspheres to upgrade immune respond,2020,-99,Universidad de Santiago de Compostela,162000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Pre-clinical studies, +C00193,unknown,TT and PT: Hidroxicloroquina for pregnant women infected by SARS-CoV-2. Hidroxicloroquina for healthy PW as COVID19 preventive treatment. Efficacy of hydroxychloroquine in preventing infection and reducing viral load and disease severity in SARS-CoV-2 infected pregnant women in Spain,"TT and PT: Hidroxicloroquina for pregnant women infected by SARS-CoV-2. Hidroxicloroquina for healthy PW as COVID19 preventive treatment.Efficacy of hydroxychloroquine in preventing infection and reducing viral load and disease severity in SARS-CoV-2 infected pregnant women in Spain It is unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes. This will be a randomized, double blinded, placebo-equivalent controlled multicentre trial aiming to assess the effect of hydroxychloroquine (HCQ) in reducing maternal viral load and the efficacy of HCQ to prevent incident SARS-CoV-2 infection. Pregnant women of any gestational age, parity and age, undergoing pre-natal follow up at four maternity hospitals with a positive PCR test, or who are contacts of a confirmed case, will be recruited and randomised 1:1 to receive HCQ orally (400 mg/day for 3 days, followed by 200 mg/day for 11 days) or ascorbic acid orally (500 mg for 3 days, then 250 mg/day for 11 days). Women will be followed up for the duration of the intervention when PCR tests for SARS-CoV-2 will be repeated, and up to delivery, when the pregnancy outcome will be registered, a cord blood sample and a neonatal throat swab will be collected after birth to be tested for SARS-CoV-2",2020,-99,ISGlobal (Barcelona),572508,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C00194,unknown,PCR: modification by isothermal which allow to reduce meaningfully diagnostic time,"PCR: modification by isothermal which allow to reduce meaningfully diagnostic time PCR: modificación de la PCR mediante isotermia, que permite reducir el tiempo del diagnóstico desde las 4 horas a los 45 minutos",2020,-99,"Instituto de Investigación Sanitaria del Hospital Clínico de Valencia (INCLIVA),",189000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00204,MC_PC_19076,saRNA SARS-CoV-2 vaccine,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. This project aims to rapidly progress a self-amplifying RNA (saRNA) vaccine against the 2019 novel Coronavirus (SARS-CoV-2) to first in human studies (phase I) within a matter of months. Within 14 days of accessing the sequence we have already designed and constructed a candidate saRNA vaccine expressing a pre-fusion stabilised conformation of the native surface glycoprotein (S-protein). This design maximises the potential for induction of neutralising antibodies while minimising the induction for off-target responses to post-fusion conformations. We have engaged key manufacturing partners able to generate GMP material not only for phase I/II studies according to a very tight schedule but also with the capability to rapidly scale to millions of doses should this be required. This cutting-edge nucleic acid vaccine platform has been specifically designed for rapid manufacture and deployment in the event of an outbreak. SaRNA offers significant advantages over other nucleic acid vaccine platforms yielding exponentially higher levels of protein expression than messenger RNA (mRNA) or DNA. The self-amplifying properties of saRNA mean that much lower doses are required to induce protective immunity, providing a significant advantage to manufacturing costs and speed. Additionally, saRNA is not limited by anti-vector immunity and is safe to administer to individuals unable to receive live attenuated vaccines (e.g. children and the immunocompromised). The Target Product Profile (TPP) is a vaccine that can be rapidly manufactured at low cost and elicit protective immunity across all at risk populations within 6 weeks of administration, with the potential for repeat boosting as required.",2020,2021,Imperial College London,2155885,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I | Unspecified",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies | Phase 1 clinical trial | Clinical trial (unspecified trial phase),2020 +C00205,MC_PC_19077,Development of an ovine polyclonal immunoglobulin therapy against COVID-19.,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The new coronavirus disease that emerged in 2019 (COVID-19) is caused by a pathogen termed SARS-CoV-2. To develop a rapid and effective therapy against infection, we are proposing to develop an ovine immunoglobulin treatment against the spike protein of this virus. Binding of antibodies to this protein will neutralise cell entry and prevent it's infectivity. Use of ovine immunoglobulin therapy is widespread for other applications, and a therapy rapidly developed for Ebola virus disease (termed EBOTAb) which demonstrated protection in guinea pigs and non-human primates. The use of polyclonal sera recognising muitiple epitopes eliminates risks of escape mutations occuring and eliminating the effectiveness of antibody therapy. This approach is also rapid, cost-effective and has a proven path to regulatory approval. To develop this therapy, recombinant spike protein will be produced in a mammalian expression system to ensure relevant protein folding and confirmation. A large batch will be produced for immunisation of sheep. Immunisations will be conducted using a facility in Australia, to mitigate risks associated with BSE. Sera will be sent to PHE for assessment of antibody levels and once sufficient antibody levels are achieved, plasmapheresis sampling will be undertaken. Immunoglobulin from these samples will be purified to develop the therapeutic material. This will be characterised at PHE for binding and functional properties before being testing using a susceptible animal model for protection against infection and disease progression.",2020,2021,Department of Health and Social Care,557150,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00206,MC_PC_19078,nCoV: Serological detection of past SARS-CoV-2 infection by non-invasive sampling for field epidemiology and quantitative antibody detection,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The escalating numbers of affected individuals in China and the potential for importation of this infection to the UK during the pre-symptomatic and potentially infectious stage renders containment problematic. Acute diagnostic PCR is of short duration usefulness in identifying those recovered from the infection. The pattern of disease is clinically diffuse rendering identification of previous infections through clinical history very difficult. Here we describe the commitment of an exceptional and highly capable scientific group who, including the PI, have previously developed specific, sensitive serology for Ebola, Zika and Lassa. The Ebola tests were instrumental in the identification of seropositive persons who had recovered silently from Ebola and characterising their antibody response. Following the same methodology for SARS-CoV-2 will allow specific detection of antibody rather than placing reliance on SARS serological assays, permitting measurement of the penetration of this infection into any susceptible population. A test format will also be developed for the non-invasive sampling of oral fluid for G and M class antibody. Recombinant envelope proteins S1 and S2 and nucleoprotein will allow the sensitive detection of antibody. Our assays, also adaptable for Point of Care and diagnostic use, will be rendered specific by described methods for conjugate quenching previously developed by the group for Zika(1). Having serology which is diagnostically important for public health, herd immunity measures will also enable establishing WHO international standards. Measurement of neutralising antibody will be important for vaccine studies and characterisation of convalescent plasma(2).",2020,2021,Imperial College London,537478.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C00207,MC_PC_19079,Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE),"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 disproportionately affects people ≥ 50 years old with comorbidities and those ≥ 65 years old. No specific treatment has yet been proven in rigorous clinical trials to be effective against COVID-19. Most clinical trials are hospital-based. Yet, most cases are managed in the community, so interventions proven to be effective are urgently in primary care that prevent hospitalisation and speed recovery. PRINCIPLE will be a Phase III, platform, response-adaptive, open-label randomised controlled trial in primary care. The platform trial will operate under a master protocol that allows the addition or replacement of further interventions. Outcome data will be analysed as the trial is in progress: if evidence emerges that one arm is more effective, we might be able to allocate more people to that arm. PRINCIPLE will, in the first instance, evaluate usual care plus hydroxychloroquine 200mg twice a day for 7 days. This drug is already in wide use, but not for this indication. The comparator will be usual care without a study drug. Eligible patients will be aged ≥50-64 years with a defined comorbidity, and patients aged ≥65 with or without comorbidity presenting within 7 days since onset of symptoms with a new continuous cough and/or high temperature during time of prevalent COVID-19 infection. Approximately 3000 eligible participants will need to be randomised in the first instance in order to determine whether the first drug we plan to evaluate is more effective than usual care alone in preventing hospital admission and/or death in people with suspected COVID-19.",2020,2022,University of Oxford,2133225,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III | Randomized Controlled Trial",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2020 +C00208,MC_PC_19080,Development of an NHP model of infection and ADE with COVID-19 (SARS-CoV-2),"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. PHE Porton's extensive experience in the development of high containment infectious disease models will be applied to set up the UK's first primate model of SARS-CoV-2 infection. This will be achieved by intra-tracheal infection using a virus stock of SARS-CoV-2 acquired through international collaboration. PHE's Victoria stock of virus has been propagated in vitro and has already been used to challenge ferrets at PHE Porton. PHE will also assess the ability of a crude (killed whole virus) vaccine to induce immune mediated disease enhancement. This will be achieved by serially immunising NHPs and then infecting them with live SARS-CoV-2. PHE will assess the clinical signs of infection as well as assessing lung pathology in-life through X-ray and/or CT imaging. In this way, if unusal pathology is observed in the immunised groups, PHE will have set up a ""positive control"" ADE model to help discriminate vaccines or therapies which assist the host or accidentally enhance the immunopathology of acquired infection.",2020,2021,Department of Health and Social Care,557172.5,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Characterisation of vaccine-induced immunity,2020 +C00209,MC_PC_19082,Healthcare Workers: an in depth virological analysis and behavioural study during the outbreak,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The further spread of the novel coronavirus SARS-CoV-2 outside China, causing coronavirus disease (COVID-19) globally has led to an outbreak that WHO announced 12 March 2020 as a pandemic. The role of Healthcare Workers (HCWs) in managing the outbreak is critical, while working in a setting where they may be inadvertently exposed to SARS-CoV-2, and WHO has prioritised research on how best to protect them from infection and disease. The similar ""Public Health Emergencies of International Concern"" caused by Zika and Ebola highlighted another important aspect: the need to integrate social sciences research into the outbreak response and to address ethical questions around studies and data sharing, in this context involving HCWs. With our proposal, we aim to integrate three key priorities in a unique way. We will leverage existing funding and our experience within the ICONIC study, funded by the Wellcome Trust/DoH (2014-18). We propose an in-depth analysis of risk of infection with SARS-CoV-2 in HCWs including longitudinal sampling, tracking of movement and studies of behaviours and influences on them (capability, opportunity and motivation). We will perform a virological analysis of infected patients with serial samples to construct a detailed analysis of transmission clusters. The latter will provide valuable clinical data on virus shedding. Finally, we propose to address the ethical questions around the use of apps and wearables, data sharing and conducting studies during an outbreak to produce a set of definitive recommendations for policy makers.",2020,2022,University College London,1829738.75,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease transmission dynamics",2020 +C00210,MC_PC_19072,Understanding Chinese government containment measures and their societal impacts,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The WHO database of research on COVID-19 contains 589 studies, the majority of which are on virology, epidemiology and clinical management. Only two (Kavanagh 2020; McCloskey et al. 2020); discuss (but do not report research on) wider governance issues. Yet the Chinese Communist Party leadership's response to the epidemic has been comprehensive well beyond clinical management. It has set up high level coordinating mechanisms across government ministries that have issued hundreds of policy documents setting out containment measures. In this way it has mobilized Party and government organizations across (for example) social care, transport, and policing that reach through local governments into every work place and community. It has used TV, print and social media to communicate measures with the public, while the public have used social media as well as self-organization to respond to measures whether by complaining and criticizing or by supporting and complementing government measures. This project will: systematically compile a database of policy documents (available from Chinese government websites) that set out containment measures as they are evolving through the epidemic; use text and computational analysis of newspapers and social media databases (Weibo Scope and WeChat Scope) we will purchase; and conduct local fieldwork (qualitative interviews) to analyse the societal impacts in urban and rural areas and responses on social media and (focussing on companies, and NGOs and citizens) in four carefully chosen localities (Hubei, Beijing, Guangdong and Anhui). The result will be important and novel resources mapping and assessing Chinese containment measures and their societal impacts, that will be communicated and updated regularly for national and international governments and organizations attempting to tackle COVID-19 around the world.",2020,2022,University of Glasgow,417453.75,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | China,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Policy research and interventions,2020 +C00211,MC_PC_19083,Gig workers: unsung heroes and a strategic role in the UK national response to the COVID-19 pandemic,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. With surging numbers of total confirmed cases and deaths, the UK has entered the most stringent social distancing stage in history. Of all the key worker groups, delivery workers is the one has most gig workers who are precariously employed. Huge spikes in demand have been reported by supermarkets, online grocers and food delivery services. The employers have responded by hiring more workers or requiring existing employees to work longer shifts. Certain epidemiological characteristics of the COVID-19, namely subclinical transmission, incubation period and varying viability on surfaces, present significant challenges to protect delivery workers. We aim to understand, based on different scenarios of risk mitigation measures and social distancing strategies, 1) how delivery workers contribute to the UK's national response by delivering to households and hence reduce number of outgoing trips; and 2) how delivery workers could potentially contribute to transmission. We will collect data from key stakeholders of the sector to understand how the supply chains and delivery workers responded to the COVID19 outbreak and to build scenarios for mathematical modelling. Using these models we will assess the impact (positive and negative) of current delivery activities, as well as additional scenarios reflecting stricter lockdown conditions, taking into account effect of risk mitigation measures, by considering the number and nature of contacts they made in the communities (including vulnerable groups). Household transmission models will be used with external forcing into households and infection back to gig workers directly considered.",2020,2021,The University of Manchester,422391.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C00212,MC_PC_19073,"Strengthening & Accelerating the Global Research Response to COVID-19 by Sharing Methods and Knowledge Between Countries, Networks and Organisations","This COVID-19 Rapid Response award is funded (100%) by the National Institute for Health Research but was part of a joint call between the MRC and the National Institute for Health Research. A Public Health Emergency was declared for COVID-19 to galvanize global collaboration to support less resources nations; this must include research to address the unknowns and ensure equity in who benefits from findings and interventions. We propose to further develop a proven mechanism for supporting locally-led evidence generation by facilitating knowledge sharing between all the networks and getting information and support to where research capacity is low. During the Ebola and Zika outbreak The Global Health Network served an important role in delivering and sharing trusted research tools, guidance and training which facilitated faster, standardised quality data capture. Beyond these outbreaks we have been working with our partners to create lasting research networks to support evidence generation in challenging settings. Here we will take our experience and add new innovative technology to make highly targeted information, tools and resources discoverable and support rapid implementation of new knowledge as this outbreak evolves. Our global partners are asking for such a mechanism, and here we can use the platform, our community, technolology and expertise to address the immediate need for global sharing and research support at this crucial point. What we learn here can then be applied to future outbreaks.",2020,2021,University of Oxford,374825,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Health Systems Research,Health leadership and governance,2020 +C00213,MC_PC_19061,COVID-19: award for MRC Unit The Gambia at LSHTM,"This award is being made in recognition that key Unit staff have been redeployed from their usual work, and Unit resources utilised, to contribute to the first phase of a rapid research response to the COVID-19 pandemic. Among their studies they are conducting a surveillance programme to document the proportion of acute respiratory illness in adults and children caused by SARS-CoV-2, performing studies to assess the prevelance of COVID-19 among pregnant women and adverse foetal effects, and studies to define the clinical presentation and understanding transmission and antibody dynamics in COVID19 infected individuals.",2020,2021,London School of Hygiene & Tropical Medicine,843750,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Gambia,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease surveillance & mapping,2020 +C00214,MC_PC_19062,Enhancing National COVID-19 Diagnostic Support Capacity in Uganda,"This award is being made in recognition that key Research Unit staff have been redeployed from their usual work, and Research Unit resources utilised, to contribute to the first phase of a rapid research response to the COVID-19 pandemic. The current coronavirus pandemic is a novel challenge for healthcare systems worldwide. The virus is currently spreading at alarming rates in Asia, Europe and North America, and it is essential that African countries prepare for the arrival and local transmission of SARSCoV- 2 and develop effective response mechanism. The African MRC Units have a critical role to play in researching the epidemic but also in supporting local health systems in this response. In Uganda, diagnostic capacity is to our knowledge currently limited to the Uganda Virus Research Institute (UVRI, Entebbe) and Central Public Health Laboratories (CPHL, Kampala). Given the rapid spread of the virus globally, there is a high risk the first positive cases will be detected in Uganda over the next few weeks. Lessons learnt from other countries suggest that the ability to rapidly diagnose SARS-CoV-2 positive samples is critical in controlling the pandemic. However, given the pace of virus spread seen in Asia, Europe and the US, the local diagnostic capacity will need to be increased substantially to handle the anticipated increase in suspected cases. The Unit has well-trained laboratory staff, robust procedures and excellent facilities which could support the national effort to prevent and contain an outbreak in Uganda. Support Capacity: The Unit intends to prepare for supporting the national diagnostic capacity by offering up to 2,500 tests per month over the next 4 months. Full virus genome sequences would be generated from a subset of positive samples, the resulting data would support the international effort in understanding the regional movement of the virus and would monitor for virus changes that might influence diagnostics or the pathology of the virus.",2020,2020,MRC/UVRI and LSHTM Uganda Research Unit,475816.25,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +C00215,MC_PC_19084,"SUPPLEMENTARY FUNDING OFFER FOR THE MRC UNIT, THE GAMBIA AT LSHTM (resource to support a clinical trial of Hydroxychloroquine and Azithromycin, studies on the transmission and antibody dynamics to SARS-CoV-2 infection, and to further support","This £4.4m award provides resource to support a clinical trial of Hydroxychloroquine and Azithromycin, studies on the transmission and antibody dynamics to SARS-CoV-2 infection, and to further support surveillance activities funded by BMGF.",2020,2022,London School of Hygiene & Tropical Medicine,5500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Gambia,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C00216,MC_PC_19027,COVID-19 Genomics UK Consortium (COG-UK),"MRC are investing £6m through the COVID-19 Genomics UK (COG-UK) consortium (COG-UK), which has received a total of £20.79m in partnership with DHSC and Wellcome, to a large scale and rapid SARS-CoV-2 sequencing capacity and share this knowledge with hospitals and the NHS. Other contributions are from DHSC and Wellcome via Wellcome Sanger. The current COVID-19 pandemic represents a major threat to health in the UK and globally. SARS-CoV-2 whole genome sequencing capacity in UK NHS clinical microbiology network and within Public Health England (PHE) is of limited daily capacity. However, the UK has world leading expertise in genomics within PHE, at multiple regional University hubs, and within large centres such as the Wellcome Sanger Institute. The proposed COVID-19 Genomics UK (COG-UK) - Consortium, will deliver a large scale and rapid SARS-CoV-2 sequencing capacity to local NHS centres and the UK government at pace. The primary achievement of this consortium will be the generation of actionable data which when combined with epidemiological and clinical information has the potential to inform interventions and policy decisions during the current UK COVID-19 epidemic. This sequencing capacity will enable real time evaluation of novel treatments and non-pharmacological interventions on SARS-CoV-2 populations and spread, and provide information on introductions versus community transmission and outbreaks. It will also evaluate signals of changing transmissibility and virulence. In the longer term, the full integration of UK population level SARS-CoV-2 genomics data, with matching NHS electronic health records, patient outcomes, human genomics and metagenomics data has the potential to generate insights into susceptibility to COVID-19 disease. Finally, the substantial new nationwide capacity in sequencing infrastructure, informatics and personnel that will be built by COG-UK will remain at the end of the COVID-19 pandemic as significant asset for the NHS, UKRI and UK Government.",2020,2023,Department of Health and Social Care,7500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified | Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Policy research and interventions",2020 +C00217,SCARD SARS-CoV-2,Development of an animal model and accelerated development of a DNA vaccine candidate (SCARD SARS-CoV-2 project),"Aims:To develop a mouse model of SARS-CoV-2 infection.This will not only enable us to evaluate the efficacy of the vaccine; it will also facilitate in vivo research on SARS-CoV-2. To evaluate the immunogenicity (ability to induce a specific immune reaction) and efficacy (protection capability) of DNA-based vaccine candidates.DNA vaccination is a technique for protecting against disease by injecting DNA encoding a specific antigen. The injected DNA triggers a protective immunological response, for example the production of antibodies against the antigen. DNA vaccines offer potential advantages compared with conventional vaccines, including the ability to induce a wider range of immune response types. Two antigen candidates have already been designed, based on the S (spike) protein of the virus, responsible for the ""crown"" (""corona"" in Latin) observed at the surface of coronaviruses, after which they were named.",2020,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies, +C00218,SARS-CoV-2_EVOLSERO,Evolution of SARS-CoV-2 and the antibody immune response in humans during infection (SARS-CoV-2_EVOLSERO project),"Aim: to understand the evolution of the SARS-CoV-2 viral population in hosts during illness, in relation with the infectivity of the virus and the establishment of the humoral (antibody-based) immune response. This knowledge is important to identify trends in disease progression and help improve the treatment and post-treatment follow-up given to patients. Detailed data on the evolution of the SARS-CoV-2 population in relation with disease progression, antiviral treatment and viral shedding sites will also be useful in evaluating links with disease severity and the potential failure of antiviral treatments. The aim is to elucidate the kinetics of SARS-CoV-2 shedding in patients with Covid-19, depending on the severity of the disease, age and existing comorbidities (shedding in upper respiratory tracts - from the nose to the larynx - and lower respiratory tracts - from the windpipe to the alveoli, or at non-respiratory sites), and also to analyze the kinetics of the viral load at respiratory and non-respiratory sites in confirmed cases according to severity, age group and existing comorbidities. The project also intends to determine the correlation between the development of the viral load and infectivity, and to understand the kinetics of introducing a neutralizing humoral response (the body's production of antibodies to neutralize the virus).",2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity | Disease pathogenesis", +C00219,FlipSARS,Development of cell lines for research (FlipSARS project),Aim: to generate a line of specific cells that will serve as a basis to improve characterization of the SARS-CoV-2 coronavirus. The generated cell lines will be useful in facilitating the isolation of clinical samples of coronavirus and in carrying out high-throughput screening,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C00220,CoV-CRISPR,A technique to identify key cellular factors for SARS-CoV-2 infection (CoV-CRISPR project),"Aim: to carry out CRISPR/Cas9 tests to identify cellular factors involved in infection with SARS-CoV-2 and antiviral proteins that inhibit its replication. These approaches will lead to the identification of key cellular factors that may serve as virulence determinants and therapeutic targets.This research particularly concerns lung cells, the main targets of the virus.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C00221,CORSER,Building a collection of human biological samples in France (CORSER project - A seroepidemiological study of the SARS-CoV-2 virus),"Aim: to detect the presence of specific SARS-CoV-2 antibodies in different populations, either those who traveled to China in the weeks preceding the start of the outbreak, or those with suspected infection with SARS-CoV-2. The aim is to understand: When and how the virus was transmitted from animals to humansWhen the virus began circulating in humans in FranceHow long the infectious period lastsWhat percentage of patients experience few or no symptomsTo answer these questions, the scientists will carry out the first seroepidemiological studies (detecting coronavirus antibodies in patients) of SARS-CoV-2 infection, while also developing a serological test. Samples will be taken:- from subjects who traveled to China during the period from August 1, 2019 to January 31, 2020 and who were not diagnosed as infected with SARS-CoV-2 (CORSER-1);- from suspected cases of SARS-CoV-2 infection that tested negative for the virus with the RT-PCR assay on a respiratory sample; contacts or individuals exposed to confirmed cases of SARS-CoV-2 infection; or individuals who worked or stayed in a hospital where confirmed cases of SARS-CoV-2 infection were treated (CORSER-2).",2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,Epidemiological studies,Disease transmission dynamics, +C00222,SARS-CoV-2-LIPS,Antibody profiling in recovering patients and development of a serological test for an epidemiological survey in individuals exposed to SARS-CoV-2 (SARS-CoV-2-LIPS project),Aim: to develop a test that can be used to carry out an initial survey on the prevalence of antibodies in individuals exposed to the SARS-CoV-2 coronavirus. The aim is to obtain a specific serological test that can be used for high-throughput testing for Covid-19 infection.,2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity, +C00223,CoronaFusion,"SARS-CoV-2 fusion, replication and host responses (CoronaFusion project)",Aim: to use cell cultures and mouse models to analyze the role of interferons and IFITMs (interferon-induced transmembrane proteins) in the replication and pathology of the SARS-CoV-2 virus,2020,-99,N/A,,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C00224,SARS-DVGs,"Defective viral genomes (DVGs), potential antiviral inhibitors of SARS-CoV-2 (SARS-DVGs project)",Aim: to use a pipeline to identify the best DVG candidates (molecules known to inhibit viral populations). The pipeline has proven effective in several virus families such as the MERS and murine (MHV) coronaviruses. The scientists propose to use the same method for SARS-CoV-2 and to test the five best DVG candidates on cell cultures. This could lead to DVGs being brought to market as an antiviral treatment for SARS-CoV-2.DVGs are defective viral genomes capable of hijacking the replication machinery of wild-type viruses and partially or totally inhibiting viral populations. Thousands of different DVGs are produced during infection by one of these viruses. The scientists have developed a method to select those most likely to have antiviral potential.,2020,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Therapeutics research, development and implementation",Pre-clinical studies, +C00225,PSII,Profiling SARS-CoV-2 intra-viral and virus-host interactions on the basis of innate immunity signaling (PSII project),"Aim: the coronavirus replication cycle depends on several protein-protein interactions, some between viral proteins to generate functional protein complexes and others with host proteins to inhibit the innate immune response. Identifying these interactions, which are essential for viral infection, can reveal the molecular mechanisms involved in pathogenesis and identify weak points in the virus that may be potential therapeutic targets.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity", +C00226,CoV-2Sensing,Working towards controlled detection of SARS-CoV-2 by the innate immune system (CoV-2Sensing project),"Aim: controlling the SARS-CoV-2 outbreak requires both scientific knowledge and antiviral drugs. RIG-I-like receptors in the cell cytoplasm play a major role in detecting infection with RNA viruses and in initiating and modulating antiviral immunity. The aim of the project is to study the RNA ligands in the SARS-CoV-2 virus that are detected by these receptors. The project will shed light on the innate immune response to SARS-CoV-2, including the harmful effects of the immune response, thereby helping identify strategies for the design of broad-spectrum antiviral drugs and vaccine adjuvants.",2020,-99,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics",Immunity, +C00227,SABSOS,A SARS-CoV-2 genome sequencing technique to analyze low-quality clinical samples (SABSOS project),Aim: viral genomics is a key tool in the response to emerging disease outbreaks like that caused by SARS-CoV-2. But sequencing can be difficult because of poor quality samples or the low ratio of viral to host RNA. This technical project will implement and optimize an approach for processing clinical samples even if they are of poor quality and have a low viral load.This method has worked for other RNA viruses (chikungunya using samples with a very low load; dengue virus using individual mosquitoes; degraded Zika virus samples),2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C00228,ONRITS,"Origins, natural reservoirs and interspecies transmission of SARS-CoV-2 and other SARS-like coronaviruses (ONRITS project)","Aim: to improve understanding of the origins, natural history and dissemination of SARS-CoV-2 and SARS-like coronaviruses in their natural environment. The main focus is to shed light on interspecies transmission (among bats, between bats and other animals, and between bats and humans); this is vital to mitigate the effects of future outbreaks like the devastating pandemic we are currently witnessing with SARS-CoV-2.It is crucial to determine which bat species serve(s) as natural reservoirs for SARS-CoV-2. This project will involve collecting biological samples (oral and fecal swabs, blood and urine samples) from bats and testing them for SARS-CoV-2 or other SARS-CoVs to determine their natural host.Bat fly ectoparasites and flying hematophagous insects (sand flies, mosquitoes and biting midges) will also be tested for the virus, since they may play a role in transmitting SARS-CoVs from one bat to another. Interactions with other animals will be observed to identify other potential hosts (snakes, civet cats or pangolins).",2020,-99,N/A,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology, +C00229,COVID-19 Serosurvey,Development of simple Covid-19 serological tools and targeted serosurvey of at-risk individuals (COVID-19 Serosurvey project),"Aim: to develop simple serological tools that can be used to establish three tests: an enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and multiplex microsphere-based immunoassays (MIAs - capable of detecting several targets). This research will pave the way for the serological investigation of at-risk individuals such as those working at animal markets, farmers exposed to bat guano (used as a natural fertilizer) and those living in rural villages in Cambodia. Biological samples are available at the Institut Pasteur du Cambodge because of previous and current research conducted by the Virology Unit.SARS-CoV-2 diagnosis has hitherto been based on molecular biology methods (RT-PCR). Serological surveys, especially in at-risk individuals, will be a vital tool in improving our understanding of the epidemiology of the novel virus.",2020,-99,N/A,,Human Populations,Asian,Unspecified,Rural Population/Setting,Unspecified,Farmers | Other,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Western Pacific,,,,,Cambodia,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00230,VAC-NAB-COV,"Spike glycoprotein, lentiviral vectors and B/T-cell vaccine (VAC-NAB-COV project)","Aims: to develop as quickly as possible:an in vitro test to detect and quantify SARS-CoV-2 neutralizing antibodies while avoiding the need to handle the virus. The test will be used to demonstrate the feasibility of vaccine candidates (proof of concept).The availability of a test of this type is crucial in searching for antibodies in samples from patients with Covid-19. These tools will be produced in large quantities and made available to all Institut Pasteur teams.a prophylactic vaccine candidate for SARS-CoV-2 based on lentiviral vaccine vectors.These lentiviral vaccine vectors encode immunogens that protect against SARS-CoV-2 viral surface proteins (spike or nucleocapsid). They will be investigated in an animal model.Lentiviral vaccine vectors are particularly useful because of their potential to induce long-lasting adaptive immune responses. Scientists have already demonstrated the remarkable protective efficacy of these vectors in mice in several situations (against infection with papillomavirus and some flaviviruses, for example) and a lentiviral vector (LV) has also been successfully investigated in a phase 1 trial for an HIV vaccine, which established its safety in humans.",2020,-99,N/A,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Diagnostics | Immunity | Pre-clinical studies, +C00231,CORONABODIES,Production of recombinant antigens from two SARS-CoV-2 proteins and generation of nano-antibodies against these proteins for diagnostic and therapeutic applications (CORONABODIES project),"Aim: to develop reliable rapid diagnostic tests for the infection that can be performed in a few minutes, anywhere and at any time, outside research laboratories; and serological tests to monitor the spread of the outbreak virtually in real time, helping with the implementation of mitigation measures.The idea is to generate the following unique tools as quickly as possible:recombinant SARS-CoV-2 nucleoprotein (N) and spike (S) antigens;nano-antibodies targeting these two proteins. These tools will be used to develop: serological tests for a serological survey of the exposed population, to help sort suspected cases and enable real-time monitoring of the spread of the outbreak;antigen detection tests that can be used for quick and effective sorting of suspected cases.Neutralization of the virus with ""anti-S"" nanobodies will also provide direct options for clinical therapeutic development.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics, +C00232,SPILLOVER-CORONA,Monitoring the origins and transmission/spread of SARS-CoV-2 in Laos and Vietnam: searching for SARS-like viruses and detecting antibodies in vertebrates (SPILLOVER-CORONA project),"Aims: - to search for other SARS-like coronaviruses in various vertebrates and arthropods.A metagenomic analysis will be carried out using next-generation sequencing (NGS) technologies on selected samples.- to detect past coronavirus infections in animals and humans exposed to the virus.This research will use antibody tests specifically developed within the Institut Pasteur's coronavirus task force for SARS-CoV-2, adapting them to the newly identified coronaviruses.The project complements (and it is conducted in conjunction with) a project at the Institut Pasteur du Laos: ""Origins, natural reservoirs and interspecies transmission of SARS-CoV-2 and other SARS-like coronaviruses"" (ONRITS) (see project 12), which aims to improve understanding of the origins, natural history and dissemination of SARS-CoV-2 and other SARS-like CoVs in their natural environment, as well as potential bat-to-bat, bat-to-animal and bat-to-human transmission mechanisms.",2020,-99,N/A,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe | South-East Asia | Western Pacific,,,,,France | Lao People's Democratic Republic | Viet Nam,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission", +C00233,2019-NCOV THERAMAB,Isolating and characterizing the human antibodies that neutralize SARS-CoV-2 (2019-NCOV THERAMAB project),Aim:to elucidate the mechanisms behind the antibody responses to SARS-CoV-2 and investigate the role they may play in eliminating the virus in infected individuals. The idea is to improve our understanding of the antibody responses of anti-SARS-CoV-2 memory B lymphocytes at molecular and functional level (B lymphocytes are the immune cells that produce antibodies). The memory B cells that develop after an initial infection have a long life span and are capable of intervening rapidly and effectively in the event of reinfection. The project aims to harness the discoveries made to develop a treatment based on the use of human neutralizing antibodies (immunotherapy).,2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies, +C00234,G4-COVID19,Characterization of interaction between SARS-CoV-2 Nsp3 protein and non-canonical nucleic acid structures (G4) present in infected cells (G4-COVID19 project),"Aim: to characterize the molecular interaction of the SARS-CoV-2 virus, and particularly two domains of its Nsp3 protein, with non-canonical nucleic acid structures present in human cells. These structures known as G4-RNA and their interaction with Nsp3 constitute new therapeutic targets. Tests developed under this project will enable research on molecules to inhibit such host-virus interaction and potentially block virus replication in infected individuals.",2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Therapeutics research, development and implementation",Pre-clinical studies, +C00235,PROTEO-SARS-CoV-2,A combination of cutting-edge proteomic approaches for improving understanding of SARS-CoV-2 infection mechanisms (PROTEO-SARS-CoV-2 project),"Aim: to characterize the cellular mechanisms of SARS-CoV-2 infection. Using several cutting-edge mass spectrometry protein analysis techniques, the team is seeking to understand how the virus interacts with human cells. They are particularly interested in cellular mechanisms that enable the virus to modify proteins in infected cells in order to reproduce. This study conducted in tandem with a comparison with other viruses from the coronavirus family may enable new therapeutic targets to be identified.",2020,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C00236,RCCOVID,Red Cross health workers and volunteers and continuity of care with COVID-19: an operational approach using mixed methods (RCCOVID project),"Aim: to study social and cultural challenges encountered by French Red Cross health workers and volunteers (who work with healthcare facilities/hospitals, nursing homes, etc. as well as those working in the field to assist migrants, homeless people, and frail and elderly people) and monitor communication in mainstream and social media to adapt the response to the pandemic in each region. By combining an ethnographic and big data approach, this project seeks to help mobilize and motivate physicians, nurses, nursing assistants, and volunteers. This work will enable the supply of appropriate equipment, measures and communication tools for their work.",2020,-99,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers | Caregivers | Health Personnel | Hospital personnel | Nurses and Nursing Staff | Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health service delivery, +C00237,hACE2-COV,Generation of animal models sensitive to SARS-CoV-2 to test vaccines or drugs (hACE2-COV project),Aim - Rapid development of animal models is of utmost importance to test the efficacy of vaccines and drug against COVID-19. The aim of this research project is to propose models whose cells express the human ACE2 proteins (huACE2) so that they are sensitive to SARS-CoV-2. The ACE2 protein is the gateway for the virus to enter cells. Researchers are proposing to use adenoviruses and lentiviruses as a vector to introduce the huACE2 gene.,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Therapeutics research, development and implementation",Pre-clinical studies, +C00238,COVIDAXIS trial,Randomized trial of Covid-19 chemoprophylaxis in healthcare professionals (COVIDAXIS trial),"Objective: To determine whether a two months treatment with hydroxychloroquine (HCQ) or Lopinavir / ritonavir (LPV / r) reduces the incidence of symptomatic or asymptomatic infections with SARS-CoV-2, compared to their placebo, in healthcare professionals exposed to the virus.In the absence of specific antiviral treatment, particular attention must be paid to prevention. Individual protective equipment can be insufficiently protective, including for healthcare professionals.If this trial confirms the efficacy of either drug, a chemoprophylaxis strategy could be extended to other populations highly exposed to SARS-CoV-2 or at risk of severe forms of Covid-19 while waiting for other preventive tools, vaccines in particular, to become available.",2020,-99,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel | Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase) | Prophylactic use of treatments, +C00239,Cov2-PIs,Development of a test to identify inhibitors of SARS-CoV-2 proteases (Cov2-PIs project),"SARS-CoV-2 proteases are essential to the life cycle of the virus and are highly conserved in the beta-coronavirus family. This is how the Cov2-Pls-project researchers will develop a high-throughput screening system to identify inhibitors that can effectively block the action of SARS-CoV-2 proteases, and thus stop the proliferation of the virus. The molecules identified could help develop, ultimately, effective drugs to control the spread of SARS-CoV-2 and limit its impact on public health and the global economy.",2020,-99,N/A,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France,"Therapeutics research, development and implementation",Pre-clinical studies, +C00240,DrugDesign_SARS2,Find potent antiviral drugs against SARS-CoV2 by targeting well identified proteins essential to the viral cycle (DrugDesign_SARS2 project),"The DrugDesign_SARS2 project aims to find effective antiviral drugs against SARS-CoV-2 that target proteins essential to the viral cycle. The project brings together the expertise of several laboratories and platforms of the Institut Pasteur International Network (Paris, Lille, Rome). The aim of the study is to examine a large number of compounds as quickly as possible using high throughput screening techniques. In a second round, the objective will be to improve the selected compounds, by chemical processes and using the data obtained by the various laboratories.",2020,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Europe,,,,,France | Italy,"Therapeutics research, development and implementation",Pre-clinical studies, +C00241,"170704, 175539","Rapid, Ultrasensitive Clinical Detection of 2019 Novel Coronavirus (nCOVID-19) by Novel Microfluidic Electrochemical Nano-Biosensors [Added supplement: COVID-19 Variant Supplement]","In December 2019, a novel coronavirus (2019-nCoV) emerged in the city of Wuhan, in China and has spread widely, including Canada. In a few weeks, the number of confirmed cases of COVID-19 infection has dramatically increased. Currently, 20-25% of confirmed cases have severe clinical presentations. With no vaccines nor specific treatments, early confirmation before progression to late stages would provide more time for effective supportive treatment. The traditional detection process requires that samples from sick individuals be transported to laboratories for manual processing. This is extremely inefficient and introduces a significant time-delay that has severe consequences for disease spread. Since January 2020, tests have become increasingly available for clinically suspected patients. However, despite the high sensitivity of these methods, they are not suitable for rapid and large-scale screening for multiple samples because of their long analysis time. Moreover, these methods need skilled personal to perform and not suitable for point-of-care testing. Most of these assays have not been yet adopted for COVID-19. The objective of this project is to develop a novel diagnostic tool for rapid detection of early-stage COVID-19. The device will have an impact to timely inform and refine strategies that stop the spread of the disease.",2020,2022,University of Calgary,596392,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00242,"170708, 175537",Design and evaluation of novel inhibitors targeting SARS-CoV-2 polymerase to create lead compounds to develop more effective treatments of COVID-19 [Added supplement: COVID-19 Variant Supplement],"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 produces a key enzyme, nsp12, essential for replicating the viral genome. In combination with the sequence of nsp12 from SARS-CoV-2, previous studies on closely related enzymes from other viruses provide insights into how nsp12 functions. Our analysis indicates how the specific structural features of nsp12 provide new opportunities for creating inhibitors with higher activity and specificity, and thus likely to act as more effective medications for treating COVID-19. Our models of the 3D structures of nsp12 bound to RNA and drugs like remdesivir indicate how existing inhibitor compounds developed to treat other viral diseases could be modified to work more effectively for treating COVID-19. We propose to synthesize a series of modified inhibitors tailored to fit the structure of nsp12 and then test the activity of these inhibitors on purified nsp12 using a previously published assay procedure. The ability of different inhibitors to disrupt the activity of nsp12 will be measured using this assay. The most effective inhibitors will be cocrystallized into a hybrid form of the norovirus polymerase to provide timely structural information about how inhibitors are likely to bind to nsp12. This structural information will help to further refine the design and improvement of the next generation of inhibitors. Promising inhibitors will be passed on to collaborators and the general community to evaluate their effectiveness in cell culture infection models and ultimately in human clinical trials. We expect to synthesize the first series of novel inhibitors within 4-6 months and to be able to evaluate their activity by the end of 2020. Additional structural characterization will take another 4-6 months. Based on this information, a second generation of inhibitors will be prepared and characterized by the end of the 2-year project.",2020,2022,University of Calgary,330700,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00243,170713,"Responding to the Stigma, Fear, Discrimination, and Misinformation Related to the COVID-19 Disease Outbreak: A Novel Analyses and Intervention for a Novel Coronavirus.","The proposed research will analyze the stigma, fear, discrimination, and misinformation related to the spread of the novel coronavirus, now referred to by the scientific name, SARS-CoV-2. Our research team will approach the problem by using several strategies to gain information from members of the Chinese and East Asian communities in Canada which have been targets of much of the stigma, fear, discrimination and even, violence, targeted at them because they are perceived to be responsible for and spreading the SARS-CoV-2 virus. First, we will conduct interviews and focus groups with members of the Chinese and East Asian communities to document and understand their experiences related to the COVID-19 disease epidemic, the scientific name now designated to identify the disease related to the new novel coronavirus. Next, we will conduct a representative survey of all Canadians which will assess their knowledge levels about SARS-CoV-2 including the prevalence, lethality, modes of infection and perceived personal risk of acquiring the virus. We will collect detailed information about aspects of participants' identities such as their gender, gender identity, sexual orientation, race/ethnicity, social class, religion, age, and other factors to provide a context for understanding their responses. We will then work to propose a model of how these various factors fit together to assist public health officials and others to understand and respond to the COVID-19 disease epidemic. Finally, we will design a social media response employing ""social influencers"" to counteract the negative message received about the COVID-19 disease epidemic and communities associated with it, and construct a website based on the principles of motivational interviewing to decrease the prejudices and stereotypes of participants and increase their health-protective responses and feelings of resilience in response to the COVID-19 disease epidemic.",2020,-99,University of Toronto,327490.8,Human Populations,Asian,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication, +C00281,01KI2048,Testing of clinically approved Camostat in preclinical human ex vivo lung culture model of SARS-CoV-2 infection,"The SARS-CoV-2 triggered a pandemic of the ""Coronavirus Disease-2019"" (COVID-19). The viral entry of coronaviruses is based on binding of the viral spike protein (S protein) to cellular receptors and on S protein processing by host cell proteases. It is known that SARS-CoV-2 uses the human receptor ACE2 for cell entry and the serine protease TMPRSS2 for ""priming"" the S protein. The protease inhibitor Camostat, which has already been used clinically, reduces cell infection. So far, this has only been shown in cell lines or cell cultures that do not reflect the complexity of the three-dimensional alveolar lung cell association with type I, type II cells, endothelial cells and alveolar macrophages. The aim of the proposed project is to test Camostat in a preclinical model of human ex vivo lung cultures to better estimate the therapeutic potency of Camostat in COVID-19. The effects of Camostat in different doses at different times of infection of human ex vivo cultivated and infected with SARS-CoV-2 lung tissue are to be tested. Viral replication and the formation of interferons and selected pro-inflammatory cytokines are determined. These are the primary relevant readout parameters in an established model, supernatants and tissue are recorded in a biobank for follow-up analyzes. Depending on the findings, the experiments can be extended to other locally available relevant human ex vivo infection models of the upper respiratory tract (nasal turbinates, mucous membranes, sinuses, tonsils).",2020,2021,Charité Berlin,62208,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +C00282,01KI2050A,CoronaVirus Interaction Network to Establish Therapies,"Viruses rely on interactions with cellular proteins in order to replicate, transmit efficiently and to cause disease. Our knowledge on interactions of coronavirus (CoV) proteins with cellular proteins is still very limited. This is particularly true for the newly emerged SARS-CoV-2, which causes Covid-19. However, such virus-host protein-protein information would not only be highly relevant to understand the biology of CoVs but also to establish intellectually designed therapies. Here we propose to join forces of two laboratories with expertise in CoV biology and viral - host protein interactions to chart the interface between coronaviruses (SARS-CoV-2, SARS-CoV and less pathogenic human CoVs) and the cellular proteome. This network of proteins will be complemented with information druggability of individual proteins in order to identify candidate proteins or drugs, which potentially modulate SARS-CoV-2 spread or pathology. We anticipate that this information will be of critical support for the current endeavour to establish therapies against Covid-19.",2020,2021,Technical University Munich,411503.76,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C00283,01KI2050B,CoronaVirus Interaction Network to Establish Therapies,"Viruses rely on interactions with cellular proteins in order to replicate, transmit efficiently and to cause disease. Our knowledge on interactions of coronavirus (CoV) proteins with cellular proteins is still very limited. This is particularly true for the newly emerged SARS-CoV-2, which causes Covid-19. However, such virus-host protein-protein information would not only be highly relevant to understand the biology of CoVs but also to establish intellectually designed therapies. Here we propose to join forces of two laboratories with expertise in CoV biology and viral - host protein interactions to chart the interface between coronaviruses (SARS-CoV-2, SARS-CoV and less pathogenic human CoVs) and the cellular proteome. This network of proteins will be complemented with information druggability of individual proteins in order to identify candidate proteins or drugs, which potentially modulate SARS-CoV-2 spread or pathology. We anticipate that this information will be of critical support for the current endeavour to establish therapies against Covid-19.",2020,2021,Justus-Liebig University GieÇ­en,184743.72,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00284,01KI2052,Hydroxychloroquine for COVID-19,"Hydroxychloroquine can inhibit SARS-CoV-2 viral replication and Chinese and French studies on COVID-19 patients suggest hydroxychloroquine is a candidate for treatment. We conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease to assess virological efficacy, tolerability and safety of hydroxychloroquine. 220 consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in 1:1 ratio to hydroxychloroquine (600mg QD on day 1-7 with an additional dose on day 1 for patients=70kg bodyweight) or placebo. Sample size is calculated to detect with 80% power and 5% alpha a reduction in time to lower level of quantification (LLoQ) from 3 to 2 weeks. Clinical and lab assessments will be done as requested by the physician or as required to analyse secondary and tertiary outcomes. Adverse events will be assessed at each visit. All other medical interventions are allowed as judged by the physicians.Primary outcome measure: Time to drop of RNA load below level of quantification in per protocol analysis (as defined by test manufacturer); Secondary outcome measures: All-cause mortality within 30 days, proportion admitted to ICU, proportion requiring non-invasive ventilation, proportion requiring invasive ventilation, reduction in viral RNA load in upper respiratory tract specimen as assessed by area under RNA load curve, reduction in viral RNA load in upper respiratory tract specimen defined as decline of RNA by 2 log-levels Safety endpoint: overall tolerability and safety of study drug; cardiac safety assessment.",2020,2021,Eberhard-Karls-University Tuebingen,2591998.92,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2020 +C00285,01KI2067A,Koordinierung und Durchführung der deutschen Beteiligung der WHO Studie Solidarity gemäß den WHO Protokollen,"The aim of the project is to enable German clinics to participate in international clinical trials that are already testing known drugs for the treatment of COVID-19. These studies include, for example, the ""Solidarity Trial of the WHO"" or the comparable DisCOVery Trial under the leadership of the French Institute de la Santé et de la Recherche Médicale (INSERM). These studies are intended to test specific active substances in as many clinics and as many countries as possible on a large number of patients, for which there are first indications of effectiveness against COVID-19. These include, for example, an antiviral drug that was originally developed for Ebola, two malaria drugs, or combinations of drugs. The studies are flexible and are closely monitored internationally, so that unsuitable active substances are quickly discarded and new active substances are quickly included in the study. Overall, scientifically reliable results should be generated faster than usual. In addition, these studies can give as many patients as possible access to new, promising therapies.",2020,2021,Justus-Liebig-University GieÇ­en,856495.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00286,01KI2067B,Koordinierung und Durchführung der deutschen Beteiligung der WHO Studie Solidarity gemäß den WHO Protokollen,"The aim of the project is to enable German clinics to participate in international clinical trials that are already testing known drugs for the treatment of COVID-19. These studies include, for example, the ""Solidarity Trial of the WHO"" or the comparable DisCOVery Trial under the leadership of the French Institute de la Santé et de la Recherche Médicale (INSERM). These studies are intended to test specific active substances in as many clinics and as many countries as possible on a large number of patients, for which there are first indications of effectiveness against COVID-19. These include, for example, an antiviral drug that was originally developed for Ebola, two malaria drugs, or combinations of drugs. The studies are flexible and are closely monitored internationally, so that unsuitable active substances are quickly discarded and new active substances are quickly included in the study. Overall, scientifically reliable results should be generated faster than usual. In addition, these studies can give as many patients as possible access to new, promising therapies.",2020,2021,Hannover Medical School,935587.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00287,01KI2087A,The Spread of the Coronavirus in Germany: Socio-Economic Factors and Consequences,"The novel coronavirus (SARS-CoV-2) first identified in China in January and the respiratory disease it causes, COVID-19, have spread around the world within a matter of weeks. To prevent the medical and health system from becoming overwhelmed by patients in need of treatment, efforts are being made to slow the spread of the disease over as long a period as possible. Due to the expected increase in the number of new infections, further measures and guidelines can be expected in the coming weeks and months that will affect virtually all aspects of people's lives in Germany. Urgent questions arise as to the medical and health impacts of the virus; the social, psychological, economic, and political factors that affect its spread; and the consequences thereof-questions that cannot currently be investigated due to the lack of a generalizable database. The planned research project aims to investigate the acute, medium-term, and long-term socio-economic factors in and consequences of the spread of the coronavirus in Germany. Based on standardized telephone surveys of a representative sample of Germany's will focus on subjective experiences, on how informed the population is, on how people are handling the crisis at an individual level, and on identifying the individual and social factors that play a role in this crisis and the consequences thereof. The survey will cover the following topics: a) health behavior and health inequality, b) labor market and economic situations, c) social life, networks, and mobility, d) mental health and well-being, and e) social cohesion.",2020,2021,German Institute for Economic Research,521118.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Economic impacts,2020 +C00288,01KI2087B,The Spread of the Coronavirus in Germany: Socio-Economic Factors and Consequences,"The novel coronavirus (SARS-CoV-2) first identified in China in January and the respiratory disease it causes, COVID-19, have spread around the world within a matter of weeks. To prevent the medical and health system from becoming overwhelmed by patients in need of treatment, efforts are being made to slow the spread of the disease over as long a period as possible. Due to the expected increase in the number of new infections, further measures and guidelines can be expected in the coming weeks and months that will affect virtually all aspects of people's lives in Germany. Urgent questions arise as to the medical and health impacts of the virus; the social, psychological, economic, and political factors that affect its spread; and the consequences thereof-questions that cannot currently be investigated due to the lack of a generalizable database. The planned research project aims to investigate the acute, medium-term, and long-term socio-economic factors in and consequences of the spread of the coronavirus in Germany. Based on standardized telephone surveys of a representative sample of Germany's will focus on subjective experiences, on how informed the population is, on how people are handling the crisis at an individual level, and on identifying the individual and social factors that play a role in this crisis and the consequences thereof. The survey will cover the following topics: a) health behavior and health inequality, b) labor market and economic situations, c) social life, networks, and mobility, d) mental health and well-being, and e) social cohesion.",2020,2021,Bielefeld University,18766.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Economic impacts,2020 +C00289,N/A,Moderna,mRNA1273 encodes for a pre-fusion stabilized Spike protein of 2019-nCoV Phase I safety and immunogenicity,2020,-99,Moderna,20000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial, +C00290,N/A,Novavax,Antigen is recombinant full-length S protein nanoparticles engineered in baculovirus and expressed in Sf9 insect cells; Adjuvant is saponin-based Matrix-M (raw material sourced from tree bark from source in Chile)Phase I safety and immunogenicity,2020,-99,Novavax,4000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial, +C00291,N/A,Hong Kong,Viral Vector / Nasal Flu construct with NS1 deletion. Includes the Receptor Binding Domain (RBD) of Covid-19 Preclinical proof of concept,2020,-99,Hong Kong University,620000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Western Pacific,Western Pacific,,,,China,China,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00292,N/A,Clover,Protein: Native-like Trimeric Subunit Vaccine Phase I safety and immunogenicity,2020,-99,Clover Biopharma,328000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Western Pacific,Western Pacific,,,,China,China,"Vaccines research, development and implementation",Phase 1 clinical trial, +C00293,N/A,Curevac,mRNA Full Length S stabilized (unmodified and codon optimized) Phase I safety and immunogenicity,2020,-99,Curevac,15300000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Europe,Europe,,,,Germany,Germany,"Vaccines research, development and implementation",Phase 1 clinical trial, +C00294,N/A,Queensland,Full length S-protein Molecular clamp (pre-fusion viral insertion proteins are stabilised using a sequence from HIV. This is applicable to type I and III glycoproteins). Phase I safety and immunogenicity,2020,-99,University of Queensland,4500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +C00295,N/A,Inovio,"DNA plasmid with electroporation, coding for full-length spike protein of SARS-CoV-2 Phase I/II",2020,-99,Inovio,22500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial, +C00296,N/A,Pasteur,"Measles Vectored-construct expressing the full length S-protein Phase I safety and immunogenicity Institut Pasteur, Themis Bioscience, University of Pittsburgh",2020,-99,Institute Pasteur,4900000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Coalition for Epidemic Preparedness Innovations (CEPI),Norway,Europe,South-East Asia,South-East Asia,,,,India,India,"Vaccines research, development and implementation",Phase 1 clinical trial, +C00297,unknown,Proof of concept: Surface optical visualization system in order to identify virus residues,Proof of concept: Surface optical visualization system in order to identify virus residues,2020,-99,Instituto de Biomedicina de Sevilla,549180,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C00298,unknown,Identification of immunoglobulin antibodies (IgG) thanks to the use of nanosensors,Identification of immunoglobulin antibodies (IgG) thanks to the use of nanosensors,2020,-99,Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA),108000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C00299,unknown,Searching for new antiviral drugs repurposing by supercomputing techniques,Searching for new antiviral drugs repurposing by supercomputing techniques,2020,-99,"Barcelona Supercomputing Centre (BSC),",211680,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Pre-clinical studies, +C00300,unknown,Nonspecific immunity to SARS-CoV-2 by MTBVAC plus BCG tuberculosis vaccine,Nonspecific immunity to SARS-CoV-2 by MTBVAC plus BCG tuberculosis vaccine,2020,-99,Universidad de Zaragoza.,343440,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C00301,unknown,SARS-CoV2 Air Transmission: Innovative Technologies for Hospital virus detection Transmisión de SARS-CoV2 por el aire: detección en hospitales y tecnologías innovadoras,"SARS-CoV2 Air Transmission: Innovative Technologies for Hospital virus detection No existen actualmente metodologías eficaces para detectar virus en el aire. Nuestro grupo ha optimizado recientemente métodos basados en filtros capaces de retener la comunidad completa de virus en el aire. SARS-CoV2 es estable en el aire durante al menos 3h y es muy eficaz en la transmisión, pero su diseminación aérea no se ha estudiado. Proponemos utilizar esta metodología para detectar SARS-CoV2 en hospitales y realizar un estudio longitudinal de la prevalencia del virus en espacios hospitalarios. En paralelo, desarrollaremos nanopartículas como métodos colorimétricos de detección sencillos, aplicables a hospitales, para monitorizar rápidamente la presencia de virus captados en el aire. Desarrollaremos sensores laser-induced fluorescence (LIF) como un método de detección directa de partículas de SARS-CoV2 y otros virus en el aire, sin necesidad de procesar las muestras",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas,517320,Unspecified,Not applicable,Not Applicable,,Not applicable,Not applicable,,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures", +C00302,unknown,Early diagnosis of COVID19 through isolation of exomes in suspected cases,Early diagnosis of COVID19 through isolation of exomes in suspected cases,2020,-99,Instituto Aragones en Cincias de la Salid,77220,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00303,unknown,SARS-COV-2 diagnosis by phi29 polymerase amplification,"SARS-COV-2 diagnosis by phi29 polymerase amplification The project aims the validation of a reliable method for diagnosis of SARS-COV-2 infection. This novel method will allow the improved detection of the viral RNA molecule by means of a virus-specific linear probe that becomes circularized only in the presence of the viral RNA. Once the probe becomes circular, an engineered form of phi29 DNA polymerase (CSIC patent licensed to 4basebio) will start copying the circular template by generating an unlimited synthesis reaction defined as ""rolling-circle replication"" (RCR), which depends on the unique and robust strand-displacement synthesis capacity of this phi29 DNA polymerase variant. This peculiar mode of synthesis, a hallmark of the isothermal DNA amplification of full genomes used worldwide, could be easily detected as a readout of the presence of SARS-COV-2 genomic RNA",2020,-99,Centro Nacional de Investigaciones Oncológicas Carlos III,21600,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00371,01KI20101,GICK - Health communication in the corona crisis,"The aim of the project is to analyze the communication channels for health information regarding the COVID-19 pandemic. To this end, the researchers are investigating the use of health-related information by various target groups in a defined region, the Münsterland, during the ""Corona crisis"". Which channels are used by different population groups and how are the contents and forms of presentation evaluated? What behavior does this entail for citizens? This is done using representative surveys and expert discussions. The project complements an ongoing study (FKZ 03IHS062B) on imparting health-related knowledge in the Münsterland region, in which it is analyzed how expert knowledge in rural areas can be optimally conveyed to various target groups. The planned work should help to optimize the communication tools and channels in health communication in the medium and long term to suit target groups.",2020,2021,Westfäfliche Wilhelms-Universität Münster,54000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2020 +C00372,01KI20130,SARS-CoV-2 T-cell epitopes for the development of new diagnostic and therapeutic approaches for COVID-19 disease (CoV2TE19),"SARS-CoV-2 pandemic currently poses a serious threat to the world population, calling for the rapid development of effective diagnostic and therapeutic tools. T-cell immunity mediated by CD4 and CD8 T cells represents a cornerstone in the control of viral infections. The knowledge of virus-specific T-cell epitopes represented by HLA-presented peptides provides on the one hand a diagnostic tool and on the other hand various therapeutic options including vaccination approaches and the transfer of virus-specific T cells or T-cell receptors, which was already proven to be effective against various viral infections. Thus, we aim within the proposed project to characterize SARS-CoV-2-specific CD4 and CD8 T-cell epitopes from all known proteins of the virus covering the most common HLA allotypes. Using ELISpot assays we will perform a high-throughput screening of 120 potential SARS-CoV-2 HLA class I and class II T-cell epitopes predicted by the established algorithms SYFPEITHI and NetMHCpan using PBMCs from volunteer donors that recovered from SARS-CoV-2 infection (SARS-VD). Validated T-cell epitopes will be further used to characterize SARS-CoV-2 immunity. This approach will finally allow to i) gain more detailed knowledge about the interaction of SARS-CoV-2 with the immune system, ii) provide novel diagnostic tools to identify and monitor people with SARS-CoV-2 immunity, and most important iii) define possible target structures for the development of virus-specific immunotherapies for the treatment of the COVID-19 disease.",2020,2021,Eberhard Karls Universität Tübingen,308434.39,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C00373,01KI20131A,SARS-CoV-2 -KIDS Study: Seroprevalence of SARS-CoV-2 (COVID-19) among children (<18y) in Germany: time series in sentinel children's hospitals,"SARS-CoV-2 is spreading rapidly and globally, but little is known about the distribution and mode of spreading in Germany. Since it is expected that COVID-19 will be comparatively harmless or even asymptomatic in children, it can be assumed that a high number of infections in this group will be not detected, causing children to act as spreaders of the infection. The aim of this study is to obtain a prospective monthly estimate of the seroprevalence of an infection with the SARS-CoV-2 in children and adolescents in Germany in the period from 01.05.2020 to 30.04.2021 in 12 sentinel children's hospitals and thereby describe the yearly course of the epidemic in children and adolescents: • What is the maximum prevalence reached at the peak of the epidemic? • When does the monthly increment flatten? • Are there differences with the temporal course by age, sex, and region? • What is the estimated burden of suffering related to the SARS-Cov-2 in children? • Does the burden of suffering vary by age, sex, ethnicity or underlying disease? • Which proportion of confirmed positive cases has been previously diagnosed by a physician or other medical experts? Data on the seroprevalence of SARS-CoV-2 in children are mandatory for understanding the previous epidemiology and for guidance of the management of the epidemic in the future.",2020,2021,Charité - Universitätsmedizin Berlin,260760.74,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease surveillance & mapping,2020 +C00374,01KI20131B,SARS-CoV-2 -KIDS Study: Seroprevalence of SARS-CoV-2 (COVID-19) among children (<18y) in Germany: time series in sentinel children's hospitals,"SARS-CoV-2 is spreading rapidly and globally, but little is known about the distribution and mode of spreading in Germany. Since it is expected that COVID-19 will be comparatively harmless or even asymptomatic in children, it can be assumed that a high number of infections in this group will be not detected, causing children to act as spreaders of the infection. The aim of this study is to obtain a prospective monthly estimate of the seroprevalence of an infection with the SARS-CoV-2 in children and adolescents in Germany in the period from 01.05.2020 to 30.04.2021 in 12 sentinel children's hospitals and thereby describe the yearly course of the epidemic in children and adolescents: • What is the maximum prevalence reached at the peak of the epidemic? • When does the monthly increment flatten? • Are there differences with the temporal course by age, sex, and region? • What is the estimated burden of suffering related to the SARS-Cov-2 in children? • Does the burden of suffering vary by age, sex, ethnicity or underlying disease? • Which proportion of confirmed positive cases has been previously diagnosed by a physician or other medical experts? Data on the seroprevalence of SARS-CoV-2 in children are mandatory for understanding the previous epidemiology and for guidance of the management of the epidemic in the future.",2020,2021,Universitätsmedizin Mannheim/Heidelberg,294865.61,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease surveillance & mapping,2020 +C00375,01KI20131C,SARS-CoV-2 -KIDS Study: Seroprevalence of SARS-CoV-2 (COVID-19) among children (<18y) in Germany: time series in sentinel children's hospitals,"SARS-CoV-2 is spreading rapidly and globally, but little is known about the distribution and mode of spreading in Germany. Since it is expected that COVID-19 will be comparatively harmless or even asymptomatic in children, it can be assumed that a high number of infections in this group will be not detected, causing children to act as spreaders of the infection. The aim of this study is to obtain a prospective monthly estimate of the seroprevalence of an infection with the SARS-CoV-2 in children and adolescents in Germany in the period from 01.05.2020 to 30.04.2021 in 12 sentinel children's hospitals and thereby describe the yearly course of the epidemic in children and adolescents: • What is the maximum prevalence reached at the peak of the epidemic? • When does the monthly increment flatten? • Are there differences with the temporal course by age, sex, and region? • What is the estimated burden of suffering related to the SARS-Cov-2 in children? • Does the burden of suffering vary by age, sex, ethnicity or underlying disease? • Which proportion of confirmed positive cases has been previously diagnosed by a physician or other medical experts? Data on the seroprevalence of SARS-CoV-2 in children are mandatory for understanding the previous epidemiology and for guidance of the management of the epidemic in the future.",2020,2021,Ludwig-Maximilians-Universität,91997.55,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease surveillance & mapping,2020 +C00376,01KI2043A,Human antibodies to SARS-CoV2 for the prophylaxis and therapy of COVID-19 (CoVER-Ab),"Given the urgent need for prophylaxis and therapy of severe CoVID-19 the project aims to rapidly identify neutralizing human antibodies (nAb) against SARS-CoV2. Antibodies will be derived from immunoglobulin heavy and light chain pairs of plasmablasts of reconvalescent CoVID-19 patients and from immunized mice, that are transgenic for the human immunoglobulin repertoire. Antibodies will be screened for binding to the S protein of SARS-CoV2 and selected based on their efficacy in SARS-CoV2 neutralization assays. Selected nAbs will be tested for efficacy and potential disease enhancement in a mouse model for pre- and post-exposure prophylaxis and in a pre-exposure non-human primate model. Partnerships for parallel clinical development will be formed as soon as the first nAb has been identified.",2020,2021,Universität Erlangen,302846.04,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C00377,01KI2043B,Human antibodies to SARS-CoV2 for the prophylaxis and therapy of COVID-19 (CoVER-Ab),"Given the urgent need for prophylaxis and therapy of severe CoVID-19 the project aims to rapidly identify neutralizing human antibodies (nAb) against SARS-CoV2. Antibodies will be derived from immunoglobulin heavy and light chain pairs of plasmablasts of reconvalescent CoVID-19 patients and from immunized mice, that are transgenic for the human immunoglobulin repertoire. Antibodies will be screened for binding to the S protein of SARS-CoV2 and selected based on their efficacy in SARS-CoV2 neutralization assays. Selected nAbs will be tested for efficacy and potential disease enhancement in a mouse model for pre- and post-exposure prophylaxis and in a pre-exposure non-human primate model. Partnerships for parallel clinical development will be formed as soon as the first nAb has been identified.",2020,2021,Fraunhofer Institut für Zelltherapie und Immunologie Leipzig,78624.32,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C00378,01KI2043C,Human antibodies to SARS-CoV2 for the prophylaxis and therapy of COVID-19 (CoVER-Ab),"Given the urgent need for prophylaxis and therapy of severe CoVID-19 the project aims to rapidly identify neutralizing human antibodies (nAb) against SARS-CoV2. Antibodies will be derived from immunoglobulin heavy and light chain pairs of plasmablasts of reconvalescent CoVID-19 patients and from immunized mice, that are transgenic for the human immunoglobulin repertoire. Antibodies will be screened for binding to the S protein of SARS-CoV2 and selected based on their efficacy in SARS-CoV2 neutralization assays. Selected nAbs will be tested for efficacy and potential disease enhancement in a mouse model for pre- and post-exposure prophylaxis and in a pre-exposure non-human primate model. Partnerships for parallel clinical development will be formed as soon as the first nAb has been identified.",2020,2021,"Deutsches Primatenzentrum GmbH, Göttingen",206573.75,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C00379,01KI2046,"SARS-MAB - Generation of murine, monoclonal antibodies against SARS-CoV-2","The aim of the project is to develop monoclonal antibodies against special protein building blocks of SARS-CoV-2. On this basis, an analytical rapid test for the specific detection of SARS-CoV-2 in patient samples, such as B serum will be established. The planned test procedure can form the basis for further research into the virus and the course of the disease and could possibly also be used in diagnostic procedures. The project builds on the BMWi-funded project ""Monoclonal antibodies for the detection of respiratory disease MERS-CoV for use in rapid tests"" (16KN073822).",2020,2021,UP Transfer GmbH Potsdam,54000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00380,01KI2077,"COVID-19: comparison of clinical, virological and immunological features in a SARS-CoV-2 patient cohort and a newly-established mouse model (Freiburg-COVID-19)","Although clinicians and researchers have been reporting new insights into SARS-CoV-2 infection at an immense rate, many fundamental questions surrounding the underlying biology of the disease remain unanswered. Owing to its unique geographic location, the Upper Rhine region rapidly emerged as one of the earliest sites of viral transmission in Germany. As the major medical center in the area, the University Medical Center Freiburg has been a focal point of patient care, establishing robust diagnostic workflows very early in the epidemic and treating severely ill patients. This project aims to provide an in-depth characterization of the innate and adaptive immune response to SARS-CoV-2 virus in both humans and animals. To achieve this goal, a tightly-linked consortium will leverage a unique synergy between clinicians in direct care of COVID-19 patients, a diagnostic department with established SARS-CoV-2 workflows, basic research expertise in studying highly-pathogenic zoonotic respiratory viruses in animal models, and technical resources allowing in-depth immunophenotyping. This project will provide urgently needed insights into the immune response to COVID-19 infection, including identification of immune effector cells and clarification of a potential cytokine storm. This information can directly aid clinicians in treatment decisions as well as provide key data for research into treatment and prevention strategies. The project will also establish an animal model of infection which will allow in-depth characterization of the disease as well as drug and vaccine tests.",2020,2021,Universität Freiburg,646902.27,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Immunity,2020 +C00381,ESRCCOVID010,Understanding Society COVID-19 study,"Understanding Society has launched a new monthly survey to look at the impact of the coronavirus pandemic on the UK population. This has been funded by ESRC though the study's discretionary budget and a £200k award from the Health Foundation. The survey covers questions relevant to the study's core priority areas on employment, income, health, family, education, civic engagement. The first wave of the COVID-19 web survey is being fielded in late April 2020 with 42,000 Understanding Society adult participants from across the UK being invited to take part. A telephone version of the survey will be issued to non-responders and for households who do not use the internet. Fieldwork for this first wave of data collection will be completed on 29 April and data should be available to researchers from the UK Data Service by late-May. Researchers will be able to link the data from the COVID-19 survey to answers respondents have given in previous (and future) waves of the annual Understanding Society survey. The survey will include core content, repeated monthly to track changes, and variable content for which Understanding Society has published an open call for researchers across the UK to propose additional questions. The first wave of the COVID-19 qustionniare covers: Coronavirus symptoms and test results; management of long-term health conditions; caring responsibilities; loneliness; employment and financial situation; home schooling; food and alcohol consumption; exercise and smoking; and mental wellbeing.",2020,-99,University of Essex,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C00382,AH/N004108/2,"Disability and Community: Dis/engagement, dis/enfranchisement, dis/parity and dissent - aka The D4D project","Disability and Community: Dis/engagement, Dis/enfranchisement, Dis/parity and Dissent (aka the D4D project) will investigate the evolving ways in which disabled people express, perform, experience and practise 'community'. The work will be informed by critical disability theory, and it will foreground the knowledge and lived experiences of disabled people. The project team brings together academics from a range of disciplines, community investigators with expertise in performance and arts practice, and community partners (including Shape, Accentuate and DRUK). Our goals are to learn from participating communities, to build understanding, to generate opportunities for connections, solidarity, resilience and activism, and to create meaningful legacies for the communities and partners involved. D4D will explore aspects of the historical, clinical, institutional, political and technological construction of disabled communities, and trace the ways in which community members have contested, rejected and embraced these varied possibilities over time. The project will facilitate agency and empowerment among participants, facilitate knowledge exchange and professional development, and create new spaces for dialogue and intervention. D4D's research question is: In what ways are disabled people connected/disconnected to/from surrounding communities, and how might they trouble existing affiliations, re-situate themselves, and re-shape communities around them? The team will explore this question while drawing on disability studies and community research literature, and engaging in continual collaboration and reflection (on issues of power, ethics and research practice, for example). There will be 8 work streams: WS1 - will explore issues of integration and marginalization, focusing on two settings: mainstream schools and the work-place. It will explore lived experience of 'inclusion'. This work will combine ethnographic studies, with a series of cultural animation workshops through which disabled participants will articulate and explore aspects of inclusion and marginalization. WS2 - will explore the ways in which technology might impact on or facilitate experiences of social belonging, by focusing on play. The steam will support methodological development, as it will involve exploring the ways in which new technologies can support the agentic participation of non-traditional research participants. WS3 - will examine the origins, development and future of the Disability Arts community. In particular, this will involve exploring the tensions within 'identity arts' movements regarding issues of affiliation and community. WS4 - this strand will explore how participants form, experience and express alternative community, as well as how they manage their (dis)placement and disqualification by mainstream society. This research will also support disabled communities critically responds to clinical practice. WS5- In this strand, arts based research will drive an investigation of past, present and future disabled communities. In particular, through the creation and exhibition of an interactive art-piece, 'Evolution', mainstream audiences will be asked to consider disability perspectives on such matters as eugenics and genetic screening. WS6 - Playful Bodies, Technology and Community will address technologies, social change and the body, and identify the implications for disability and community, while drawing on player studies, social media research, collaborative game design, and public play. WS7 - Ethics, reflection and learning for participation will inform all the above activities and support the practices and professional development of all those taking part. WS8 - Will provide a forum for skill sharing and knowledge exchange across all streams, and work to maximize impact across and beyond the academic.",2020,2020,Bath Spa University,1457395.02,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Social impacts,2017 +C00383,AH/N004655/1,Language Acts and Worldmaking,"Language Acts and Worldmaking' argues that language is a material and historical force, not a transparent vehicle for thought. Language empowers us, by enabling us to construct our personal, local, transnational and spiritual identities; it can also constrain us, by carrying unexamined ideological baggage. This dialectical process we call 'worldmaking'. If one language gives us a sense of place, of belonging, learning another helps us move across time and place, to encounter and experience other ways of being, other histories, other realities. Thus, our project challenges a widely held view about ML learning. While it is commonly accepted that languages are vital in our globalised world, it is too often assumed that language learning is merely a neutral instrument of globalisation-a commercialised skill set, one of those 'transferable skills' that are part of a humanities education. Yet ML learning is a unique form of cognition and critical engagement. Learning a language means recognising that the terms, concepts, beliefs and practices that are embedded in it possess a history, and that that history is shaped by encounters with other cultures and languages. To regenerate and transform ML we must foreground language's power to shape how we live, and realise the potential of ML learning to open pathways between worlds past and present. Our project realises this potential by breaking down the standard disciplinary approaches that constrain Spanish and Portuguese within the boundaries of national literary and cultural traditions. We promote research that explores the vast multilingual and multicultural terrain constituted by the Hispanic and Lusophone worlds, with their global empires and contact zones in Europe, the Americas, and Africa. Understanding Iberia as both the originator and the product of global colonising movements places Iberian Studies on a comparative, transnational axis and emphasizes diasporic identities, historic postcolonial thinking, modern decolonial movements and transcultural exchange. Our research follows five paths linked by an interest in the movement of peoples and languages across time and place. 'Travelling concepts' researches the stories and vocabularies that construct Iberia as a cultural crossroads, a border between East and West, a homeland for Jews, Muslims and Christians. We examine the ideological work performed by the cultural semantics Iberia, Al-Andalus, and Sefarad in Spanish, Portuguese, English, French, German, Arabic, Hebrew and ladino (Judeo-Spanish), from the Middle Ages to the present, in Europe and beyond. 'Translation acts' turns to the theatrical narrative, investigating how words, as performed speech and embodied language create a world on stage. Through translation, we travel across time and space, interrogating the original words and bringing them to our time and place. This strand exploits theatre's capacity to (re)generate known and imagined worlds. 'Digital Modelling as an act of translation' examines the effects of digital, mobile and networked technology upon our concept of 'global' culture, and what kinds of 'translation' are enacted as information enters and leaves the digital sphere in the context of Hispanic and Lusophone cultures. 'Loaded Meanings and their history' demonstrates the centrality of historical linguistics to cultural understanding, by investigating the process and significance of the learned borrowings in Ibero-Romance. Such borrowings acquire 'loaded' meanings that reflect and shape people's attitudes and worldviews. Finally, the agents of language learning-teachers-are the focus of the fifth strand, 'Diasporic Identities and the Politics of Language Teaching'. Updated with Covid Response - Language barriers prohibit the real understanding of experience in diverse societies and lead to misunderstanding, xenophobia and violence, as we have seen in this country. Language Acts and Worldmaking, led by PI Professor Catherine Boyle, is uniquely placed to offer significant insights into its global narration. Our multidisciplinary team will lead a process of digitally mining sources from, for example, European languages, Mandarin, Korean and Arabic. Linguists working in these languages will engage in translation of the most salient terms and we will use digital tools to compare and analyse the ways in which the pandemic has been narrated. We know from our literary, cultural, linguist and historic research that words like war, conflict, contagion, invasion, fear, sanity and cleansing inhabit the ways in which we articulate our responses - collective and subjective - to moments of crisis. It is important that we have a clear understanding of these articulations at the present moment in an already volatile geopolitical situation.",2020,2021,King's College London,3587051.06,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2016 +C00384,AH/P005888/1,"HEARTS. The Health, Economic and Social impact of ARTS engagement: a Public Health Study","In the past few decades, there has been a surge of international interest in the role of the arts and culture in healthcare, public health and health promotion, on an individual and community level. However, the vast majority of research studies have focused on the effects of targeted, time-limited arts interventions on particular patient groups. Yet, much of the arts and cultural engagement across the UK is not confined to specific interventions but involves a more general, ubiquitous participation that can be harder to measure through experimental studies. A select number of public health studies have found associations between cultural participation (including attending concerts, museums and galleries) and self-reported health, as well as inverse associations between cultural participation and mortality risk. However, important questions remain, and to date, there have been no large-scale public health studies examining the impact of the arts in the UK. This project is led by the Centre for Performance Science, an internationally distinctive partnership of the Royal College of Music and Imperial College London, with an extensive track record in arts, health and social research. It explores the effect of (i) activities that involve actively 'doing' (e.g. music, dance, art, photography and drama) and (ii) activities that require physical attendance (e.g. attending concerts, monuments, museums, galleries, cinemas, heritage archives and theatre); (iii) 'home-based' activities (e.g. listening to the radio, watching TV, reading, storytelling, using arts-based apps, digital arts experiences, online music co-production). Our research questions identify the impact of the arts and culture on individual, social and economic measures of health and wellbeing, as well as explore how associations vary between different socioeconomic, geographical and ethnic populations within the UK. To explore these questions, the project is organised into four work packages. Work package 1 will involve assessing existing data including undertaking a meta-analysis of previous studies and exploring a UK cohort study that includes some questions on the arts. However, recognising the limited data currently available, work packages 2 and 3 are based on a large-scale national survey to be carried out during our study. Open to all adults in the UK, the survey will target the general population as well as participants diagnosed with one of four major health conditions facing the UK: mental health, cancer, cardiovascular disease and chronic respiratory diseases. These conditions have all previously been researched in smaller arts-in-health intervention studies but not at a public health level, and their inclusion will facilitate understanding of the relationships between culture and the individual, social and economic facets of health and wellbeing. A total of 25,000 participants will be recruited to complete an anonymous online questionnaire consisting of demographic questions, validated psychological scales and economic metrics, assessments of arts and cultural participation and self-reporting of health. Work package 2 will explore the questions with a cross-sectional analysis of these data with nested case-control studies; work package 3 will monitor a sub-section of the sample as a cohort for the following year with 6-monthly updates to track longitudinal change in arts engagement. Recognising the complexity of cultural engagement and health, work package 4 will add context to the survey data, with a sub-sample of survey participants taking part in qualitative telephone interviews to explore motivations for, and experiences of, arts engagement across the UK and how this is reported to intersect with health behaviours, perceptions and outcomes. Through the extensive epidemiology methods proposed, an ambitious sample size and nested qualitative data, the findings promise to redefine the value of the arts and culture for public health in the UK.",2020,2021,Royal College of Music,992760.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2018 +C00385,AH/R001863/1,"Paths of resistant pathogens in hospitals: architecture, design interventions, transmission risks","Paths of resistant pathogens' will map and visualise the paths that pathogens take through hospitals in order to model exposure and transmission risks. The project aims to minimise risks and prevent the spread of pathogens by making hand hygiene compliance easier through design interventions. The emergence and spread of antimicrobial-resistance (AMR) is a growing concern to global health. An estimated 700,000 people already die every year of resistant infections. Improving infection prevention and control is one important strategy to combat AMR. However, traditional approaches have shown limited benefit. For instance, educating healthcare workers to achieve higher rates of hand hygiene compliance has proven short-lived and ineffective. In this project we are building on existing design research, which has begun to shed light on the powerful role design can play in behaviour change, such as the location of sinks in increasing hand hygiene compliance. We will take this tradition of design research one step further by asking who complies and who contributes most to the potential spread of pathogens. We will achieve this by focusing on the different types of agents populating the spaces around patients: doctors, nurses and other healthcare workers, but also frequently overlooked groups such as porters, cleaners, food service workers, medical students, volunteers, etc. We will carry out a detailed analysis of architectural layouts based on space syntax techniques, which map the potential to encounter other people arising from the geometry of the building. Spaces that by the nature of their strategic location in the wider hospital system attract more flow of traffic will carry higher risks of spreading pathogens. Depending on where agents go, what or whom they touch, whether and where they wash their hands, and whether they bring along mobile items (potentially shared with and touched by others), different transmission risks may emerge. We will create visualisations of the paths that pathogens may take, as well as estimate exposure patterns and risks for each agent path. Agent behaviours accruing the highest risks will become targets for design interventions. To create appropriate design interventions, we will use a participatory approach. We will invite the different agents populating wards as well as hospital stakeholders (such as hospital management and directors of infection control) to co-creation workshops, where we will present our findings on transmission risks and spatial practices of agents. Listening to their experiences and reflections, we will create - together with them - a brief for design interventions in order to make compliance easier and improve infection control. Design responses will build on the collected data and depend on the co-creation process, but generally we can see opportunities arising from architectural modifications of layouts, adapting the locations of certain functional programmes and improving compliance by installations or a designed piece of interactive furniture. Leveraging the role of design to subtly nudge people to modify their behaviours, we envisage this project as a starting point of a wider conversation between design research and medical science.",2020,2019,University College London,243289.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings,2018 +C00386,AH/R002037/1,"Pathways, Practices and Architectures: Containing Antimicrobial Resistance in the Cystic Fibrosis Clinic (PARC)","Antibiotics may suppress infections without eliminating them, giving rise to antimicrobial-resistant (AMR) bacteria and cross-infection between people. This project is both timely and important because of the increasing numbers of bacteria acquiring resistance to existing antibiotics. Our research compares the way three outpatient lung infection clinics attempt to control AMR and cross-infection through the design, practices and architectural layout of their built environments. It further seeks to learn lessons from this to limit AMR in wider healthcare settings. The PARC project has been co-designed in close collaboration with our three partner cystic fibrosis (CF) clinics. CF is just one of many life-threatening conditions characterised by long-term antibiotic treatment giving rise to cross-infection. In turn, cross-infection leads to clusters of highly resistant bacteria which significantly reduce life expectancy and now threaten to reverse recent improvements in survival. Dialogue with our clinical partners highlights the very different material and design approaches taken to prevent cross-infection through physical isolation, segregation and containment. Despite these variations, detailed research into questions of design and practice within the built environment of respiratory clinics is sparse. This research will be significant because CF clinics have much to learn by reflecting on their own practices. They also have much to learn from each other, and much to offer the wider clinical community in limiting AMR. Our focus on CF as an exemplar has far broader relevance in design approaches to AMR mitigation in more common respiratory disorders and in infection control more generally. This research will make visible the different and sometimes competing AMR design priorities of key stakeholders (including people with CF, clinicians, designers, hygiene personnel, etc.). It will map the differing 'real world' pathways and journeys through each clinic. It will explore how physical interaction, contact and exchanges are managed through the layout of the clinics. It will also enable our partner clinics and their users to explore scope for redesigning practice and repurposing clinical space to limit AMR and cross-infection. Our project involves an innovative combination of visual and qualitative research methods. We will be using the architectural layout plans of each clinic as a focus for interviews with patients, clinicians, hospital estates personnel, hygiene staff and designers. Our interviews will also draw on the skills of the project's graphic artist who specialises in fieldwork illustration to visually record real world experiences and journeys. We will also be undertaking 'walking interviews' placing our respondents within the flow of their routines, and using photography to chronicle risky spaces and objects. The project has an observational component to document key sites of high risk within the clinics including waiting areas, reception desks, corridors, wash basins and hand sanitisers, etc. These visual, graphic and textual findings will subsequently be used in co-design workshops at each of the clinics to improve present and future AMR mitigation. The project brings together the expertise of a highly multidisciplinary team involving an academic architect, sociologists of medicine and science, micro-biologists and a graphic artist. PARC will have a positive impact upon: our three partner clinics who have been involved in the design of the project; people with CF and the CF Trust; the wider respiratory healthcare community, the NHS and Department of Health; healthcare designers and architects; policy making on AMR.",2020,2020,University of York,245423.31,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings,2018 +C00387,AH/R002088/1,AMRSim: A Microbial Reality Simulator,"Antimicrobial-resistant bacteria are an established and growing issue in small animal veterinary practice in the developed world. The problem is, people can't see the bacteria on them, on animals, or on the surfaces and objects they touch. This makes it difficult to prevent and control infection in the most effective manner, as habits and standard practice are hard to change if you don't know what you are dealing with. While data exist to inform best practise in infection control, they are usually published in academic journals, thus having limited impact on what is done in practise. Our solution is to make the 'invisible, visible' by building a three-dimensional graphical simulator of the interior of a veterinary practice in which humans, animals, and bacteria interact, according to rules observed from real-life. We are calling this simulator, AMRSim - A Microbial Reality Simulator. The indoor environment of the vet practice can be viewed as a complex 'ecosystem' in which animals and humans interact with one another and their physical environment. Within this ecosystem there is a third, unseen group of actors - microbial agents - some of which have the capability to cause infectious disease in animals and/or humans. In the case of bacteria, they often persist in the environment on surfaces as a community. It is within these bacterial communities that they are more resistant to physical or chemical removal and are able to exchange mobile genetic elements that confer resistance to antibiotics. For this reason, activities such as disinfecting surfaces, sterilising instruments and treating patients with antibiotics, are a fundamental part of the working life of health professionals. AMRSim will take data from the real world and make them 'come alive' in a visual way. Actual video footage will be used of the movements of humans and animals within a busy vet practice and the procedures undertaken, including those intended to reduce infection. The bacteria within the simulation will be introduced according to what is known of bacterial infection (types, location, antibiotic resistance) within vet practices from data already avaliable. Importantly, AMRSim will allow these normally invisible bacteria to be 'seen' as they multiply and spread through the indoor environment on people, animals and surfaces. By 'seeing' the interactions of animals, humans, and bacteria within space and time it will be possible to improve efforts to prevent bacteria entering and spreading through the physical environment, and improve their removal when they do. AMRSim will be brought, at progressive stages of its development, to a series of co-design workshops with end-users to ensure it is made meaningful, appropriate and usable, and addresses key learning outcomes with respect to preventing and controlling infection. The theory we shall test is that as practitioners interact with AMRSim, both in its development and then in its application, they will gain a greater appreciation for: 1) the impact their behaviours and activities can have on infection; 2) where weaknesses lie in current practise; and 3) where changes made to the way people and animals interact with each other and their environment can disrupt the status quo. These will lead to a reduced risk of bacterial contamination and infection, and ultimately reduced reliance on antibiotics. Our previous work in the human health environment has shown the power of 'making the invisible, visible' by simulating infection control on a hospital ward using a visual simulator. We shall build on this experience with a new, multidisciplinary team with expertise in digital design, spatial design, co-design, environmental psychology, veterinary practice, and microbiology. It is our intention that the experience we gain in developing and using AMRSim will be applied more widely, such as for teaching students and to simulate other indoor environments where biosecurity is paramount.",2020,2019,Glasgow School of Art,246386.51,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Veterinarians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC at the human-animal interface,2017 +C00388,AH/R002126/1,Re-envisaging Infection Practice Ecologies in Nursing (RIPEN) through Arts and Humanities Approaches,"Antimicrobial resistance (AMR) and its consequences pose serious threats to health and welfare globally. Across the world nurses constitute the largest professional healthcare workforce and typically nurses have numerous daily interactions with healthy and ill individuals, family members, community groups and other care professionals. As such nurses have huge potential to make every contact count to reduce inappropriate prescribing and demand for antibiotics, and to enhance the effectiveness of those prescribed. However evidence on nursing's engagement with AMR indicates that the profession has not yet leveraged its potential to prevent AMR advancing or to countenance the consequences of failure. Within this context the invisibility of pathogens and related AMR processes in everyday practice make AMR a relatively abstract issue. Based on our cross disciplinary research work involving contemporary visualisations of the pathogens, people and places that constitute practice ecologies, and on our historical research detailing eras of infection control practice in hospital settings, we believe that there is significant opportunity to enhance the meaningfulness of AMR for practicing nurses through expanded application of arts and humanities approaches. Thus we will address the main question: How can relevant arts and humanities based approaches help nurses to re-envisage their infection control practice ecologies in response to antimicrobial resistance? In doing so we will investigate four subsidiary questions: 1)How do groups of hospital and community based nurses understand and respond to the priorities and consequences of AMR within the context of their everyday working lives? 2)How can co-design and visualisation based approaches help these nurses to identify and construct sets of meaningful practices that optimise present prevention of AMR? 3)How can co-design, visualisation, history and other relevant arts and humanities approaches help nurses to re-imagine and re-envisage their infection control practice ecologies in a future with minimal or no effective antibiotics? 4)What priority issues and other questions does this initial enquiry raise, and how can these best inform policy and planning, education and further research? Following a preparatory phase the main qualitative research will engage a group of hospital based nurses in Glasgow and a group of community based nurses in London. Structured around four sequential workshops with interim activities, these respective ""Labs"" will each address questions 1-3 using and evaluating different combinations of methods. The final phase of the research will involve a ""Policy Lab"" where the research team, advisory group and an invited range of policy experts and art and humanities academics will address question 4. Through these means this novel study will produce the following deliverables: a.Project outputs (e.g. journal publications) that demonstrate enhanced understanding of the nature and scope of nurses' engagement with AMR in a range of built environments including hospitals, GP surgeries and people's homes b.Sets of prototyped AMR-related prevention practices that nurses believe they can meaningfully enact within these practice contexts c.Project outputs in a variety of possible formats (written, visual, web-based) that demonstrate how nurses can re-envisage their infection practice ecologies in a future with minimal or no effective antibiotics d.Identification of a set of priority issues and other key questions that arise from the enquiry and will inform a policy brief e.An overarching analysis of the challenges, strengths and added value of deploying particular arts and humanities approaches within a health services research context These will be of value to clinicians, the public as health service users, managers, planners and academics, and will yield potential for further practice, policy, research and educational developments.",2020,2020,Glasgow School of Art,260697.01,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health service delivery,2018 +C00389,AH/R002177/1,Understanding the home as a source of infection of AMR bacteria carried by dust by exploring hygiene practices in different home environments in Ghana,"The Dust Bunny project will apply design methods coupled with microbiological analyses to address issues of home-based infections in Ghana, particularly those carrying antimicrobial resistance, resulting in a reduction of infection and in positive increase of health outcomes. Bacteria found in the natural and built environment (e.g. homes, schools, hospitals, etc.) are building up a resistance to drugs -changing to protect themselves against antibiotics. What this means is that in the not-too-distant future, something as simple as a minor cut infection could become life-threatening. This is such a concern that antimicrobial resistance (AMR) is now considered a global health crisis, far surpassing outbreaks of diseases such as Ebola and as real as climate change. This is even more evident and critical in developing countries in Africa, such as in Ghana, where there are a great number of deaths from infectious diseases. Bacteria are made up of pathogens (bad germs) and non-pathogens (good germs) and are generally scattered across the home. Most surfaces in the home are covered to a certain degree with bacteria, but unlike fixed surfaces such as kitchen work surfaces and furniture, dust can move more easily around different parts of the home and therefore presents a major route for human exposure to bacterial infections. Despite being clear evidence for microbial exposure and infection transmission within the home, there has been less research effort invested in understanding the home environment, due to difficulty of conducting detailed studies. Although the transmission routes by dust in the home environment are well known, what has not been studied is how to prevent bacterial infection at home and thereby reduce resistance. Particularly in developing countries, such as Ghana, social inequalities mean a range of different quality and types of homes; this combined with often poor levels of domestic hygiene that is influenced by a number of economic, educational and religion factors, contributes to the spread of infectious diseases. Although there are hygiene guidelines available for preventing infection in the home environment, these are targeted at hygiene professionals and do not reach the everyday household in Ghana. There is therefore a much-required and unmet need to identify, understand and develop domestic hygiene practices that are relevant to different home environments, educational and cultural backgrounds in developing countries, such as in Ghana, in order to reduce exposure to bacteria pathogens and thereby exposure to resistance forms. Within this context, the Dust Bunny project aims at developing an understanding of the home as a source of infection of bacteria, resistant to antibiotics, found and carried by dust. This will be done by exploring hygiene practices across different home environments in Ghana, with the ultimate aim to reduce bacterial infection in the home environment thereby reducing AMR. Understanding the hygiene practices in the household and interactions with airborne AMR bacteria will serve as a first step to designing appropriate education/information dissemination materials for various sections of the Ghanaian population as well as other low- and middle-income countries in Africa. Dust Bunny, uniquely combines design research and microbiology to provide an informed assessment of societal practices in domestic cleanliness and novel solution to reduce infections in the home. The project team includes Imagination@Lancaster -an internationally leading research institution in design research- and the Noguchi Memorial Institute for Medical Research -a research centre of excellence and the prime biomedical research institution in Ghana, involved with the Ghana Health Service and Ministry of Health in providing the evidence to effect policy changes.",2020,2020,Lancaster University,260574.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Ghana,Ghana,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2018 +C00390,AH/S004564/1,ART/DATA/HEALTH: Data as creative material for health and wellbeing,"ART/ DATA/ HEALTH creates an innovative and interdisciplinary process that offers disadvantaged groups and the public new tools, at the intersections of data science with art practice, to approach two key issues in healthy aging and prevention: digital skills and health literacy. There are three main reasons for bringing cultural participation and digital inclusion together for health and wellbeing: First, there is strong evidence showing that participation in the creative arts can help promote well-being and health in communities, and can be particularly beneficial for disadvantaged groups (in terms of age, disability, income and unemployment). As technologies change, there are new questions that art and humanities research can help us address in relation to health and wellbeing. Arts-based inquiry that involves health data analysis can be an innovative intervention for public health projects. Second, critical health literacy is considered key to empowerment, as it not only improves people's capacity to use health information, but also helps them gain greater control over life events. But as health promotion and communication moves to a digitised era, health literacy today includes the capacity to efficiently use digital health technologies and being able to critically analyse information presented online. In Britain, 12.6 million people lack digital skills and they are most likely to suffer from poor health, while in most cases they also belong in disadvantaged social groups. Third, today scientific data and statistics of all sorts are being used in infographics, data journalism, design and art in order to create meaning from the deluge of big data. Data is considered the material of our times. Data-based art can help raise awareness about the ethical, social and cultural issues of personalised medicine, but is however still missing from public health, community-based initiatives. This Rutherford/Inter-disciplinary Interface Innovation Fellowship uses health data as the source of experiential stories and as the source material for creative expression. In a series of exploratory workshops, a community of artists, academics and members of disadvantaged population will use a combination of creative media, storytelling and data analytics to explore evidence around health in their local communities. They will co-produce creative work that takes various forms (such as 3D-printed data sculptures, sound art and data murals around the city), which is inspired by both anonymised personal and statistical health data. The project will contribute to the development of new theorisation and practice in the emerging field of data studies, creative arts and health in three ways: - It seeks to explore the new opportunities that are offered in data analysis and visualisation for developing participatory communication strategies for health and wellbeing in the era of big data and personalised digital health. Through innovative artwork that translates obscure statistical data into actionable health information, it will provide a unique new experience for audiences. - Secondly, it aims to examine how art and creativity can enable health literacy and digital skills amongst socioeconomically disadvantaged population to reduce health inequalities. Based on the premise that people's encounters with personal data help self-discovery, sense-making and storytelling, the project will contribute to a new approach to understanding healthy ageing, which involves digital and cultural participation. - Finally, it intends to assess how a participatory arts/data interface can benefit public health and how the combination of digital inclusion and cultural participation can help people stay healthy, active and productive as they age. By drawing on lessons from art for health initiatives, it will provide knowledge on improving public health communication strategies and on designing engaging art interventions in the care sector.",2020,2021,University of Brighton,246320.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing | Digital Health | Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Communication | Individual level capacity strengthening,2019 +C00391,ESRCCOVID011,Rapid evidence review: the effects of social isolation,Drawing together key evidence on the effects of social isolation and identifying key evidence gaps,2020,-99,King's College London,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C00392,IAA-OXF-1,Rapid testing technology for COVID-19,"Impact Acceleration Account Funding: Rapid testing technology for COVID-19:Scientists from University of Oxford and the Oxford Suzhou Centre for Advanced Research (OSCAR) have developed a rapid testing technology for the novel corona virus SARS-CoV-2 (COVID-19). The team, led by Professor Zhanfeng Cui and Professor Wei Huang, have been working to improve test capabilities as the virus spreads internationally.The new test is much faster and does not need a complicated instrument. Previous viral RNA tests took 1.5 to 2 hours to give a result. The research team has developed a new test, based on a technique which is capable of giving results in just half an hour - over three times faster than the current method.Additionally, the technology is very sensitive. This means that patients in early stages of infection may be identified sooner, potentially helping to reduce the spread of the coronavirus SARS-CoV-2 (COVID-19). The technology only requires a simple heat-block which maintains a constant temperature for RNA reverse transcription and DNA amplification, and the results can be read by the naked eye. This makes it potentially useful in rural area or community healthcare centres.The technology has been validated with real clinical samples at Shenzhen Luohou People's Hospital in China. Shenzhen Luohou People's Hospital has applied the rapid detection kits on 16 clinic samples, including 8 positives and 8 negatives, which have been confirmed by conventional RT-PCR methods and other clinical evidence. The test results using the rapid detection kits were all successful.The Oxford scientists are now working to develop an integrated device so that the test can be used at clinics, airports, or even for home use. The project was initiated by Oxford Suzhou Centre for Advanced Research (OSCAR), a University of Oxford centre in Suzhou Industrial Park, China. The experiments to develop the technology were performed in the Department of Engineering Science.",2020,-99,COVID-19 Community based surveillance for communities affected by extractive,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Western Pacific,Western Pacific,,,,China,China,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C00393,IAA-OXF-2,OxVent Prototype Ventilator,"Impact Acceleration Account Funding: OxVent Prototype Ventilator:OxVent is a multidisciplinary team of engineers and medics at the University of Oxford and King's College London. The team has been shortlisted by the UK government to go to the next stage of testing for safety and usability for their ventilator prototype.A team, led by Oxford Professor Andrew Farmery, Engineering Science Professors Mark Thompson and Alfonso Castrejon-Pita and DPhil student Rob Staruch, and King's College London's Professor Sebastien Ourselin and Dr Federico Formenti, have defined a simple, safe and scalable design that will meet the strict specifications for use with patients. The design will exploit off-the-shelf components and equipment with elements that can be produced through 3D printing techniques.If the ventilator passes the required MHRA safety tests, it will rapidly move into production with the medical manufacturing company, Smith and Nephew (S&N) based in Hull.This green light enables the team to test their prototype ventilators, developed in response to the coronavirus pandemic and forecasted acute shortage of ventilators. The next stage would be the manufacture of 6,000 ventilators and deployment through the NHS. The design could also be used in other healthcare settings.",2020,-99,industries in Peru.,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Medicines, vaccines & other technologies", +C00394,ATI-1,DECOVID,"DECOVID aims to address urgent questions that are actionable to frontline clinical and operational staff at a local (NHS hospital) level to support better care and management in the time scale of the COVID-19 pandemic; from being reactive to predictive; to inform what best practice could be, and then share this as rapidly as possible across the NHS and beyond. Our approach is to establish a unique granular, acute care medical database during the COVID-19 crisis, by targeting digitally mature hospital trusts (those with electronic health records) and incrementally collecting all acute care activity across all NHS Trusts to support high quality data capture from the start to the end of the current pandemic. These data will in turn be linked into existing national datasets, such as from primary care, in order to allow for greater understanding into the pre-morbid states of patients with the coronavirus, and therefore the window of intervention.",2020,-99,Alan Turing Institute,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C00396,RFI-1,Protein reagents,"Protein reagents: Protein Production UK based at The Franklin are developing reagents in collaboration with other Franklin structural biologists which will stabilise selected SARS-COV-2 proteins for further analysis including imaging. The selected proteins are key targets for therapeutics and vaccines Collaborators: University of Oxford, Diamond Light Source, The Research Complex at Harwell (https://www.rfi.ac.uk/science-minister-hails-nanobody-breakthrough/)",2020,-99,Rosalind Franklin Institute (RFI),,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C00397,RFI-2,Imaging technologies,"Imaging technologies: As part of an ongoing collaboration with SPT Labtech, we will be using our nationally unique capability and knowledge of the Chameleon system to improve Cryo-EM imaging of SARS-COV-2 components. SPT Labtech, Diamond Light Source",2020,-99,Rosalind Franklin Institute (RFI),,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C00398,RFI-3,Chemical biology,"Chemical biology: The Chemistry and structural biology teams are working with partners worldwide to develop novel anti-virals and diagnostics Collaborators: Members of an EU research consortium, University of Oxford",2020,-99,Rosalind Franklin Institute (RFI),,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies, +C00399,EP/P027261/1,Future Additive Manufacturing Platform Grant,"Engineers at the University of Nottingham have designed a PPE face shield with CE approval that they are 3D printing at scale for healthcare workers to use in the fight against COVID-19. Using the latest in Additive Manufacturing (3D printing) technology and materials at the University's Centre for Additive Manufacturing, and working with external collaborators, the team will deliver 5,000 of the face shields to Nottingham's NHS and community healthcare workers. Building on an open-source design of headband originally from HP, the team in the Faculty of Engineering made modifications to ensure the face shield could pass a regulatory test1 by BSI, the UK's national standards body, to meet its essential health and safety requirements which ensures the highest level of protection is provided. The face shields successfully passed the BSI tests and are CE approved1 for use as part of PPE for healthcare workers' protection against COVID-19 in both hospital and community environments. They are provided in packs to the NHS, with five replacement visors per face shield as well as instructions for use. The team have made the design and its accompanying documents 'open-source' to enable other manufacturers to produce the face shields - however, manufacturers will need to submit their product for testing to the BSI to obtain their own CE certification.",2020,2021,University of Nottingham,2127155.42,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2017 +C00400,EP/N020863/1,SPECIFIC IKC Phase 2,The EPSRC-funded SPECIFIC Innovation and Knowledge Centre led by Swansea University have built a manufacturing plant for hand sanitiser and have been delivering it to local NHS organisations. They are also working on technology for ambulance decontamination and sensors for use with ventilators to check that patients are getting enough oxygen,2020,2021,Swansea University,2451961.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2016 +C00401,EP/S001859/1,SynbiCITE 2.0,"Synthetic biology workflows drive higher throughput testing. The approach, led by SynbiCITE Co-Director Professor Paul Freemont, originates from the flexible and adaptable nature of automated synthetic biology workflows. Using the 'design, build, test, learn' approach that is fundamental to synthetic biology, Professor Freemont and a team from the Dementia Research Institute and Imperial College London, used the London BioFoundry's Felix robots to design new workflows to carry out COVID-19 antigen testing using the standard PCR.",2020,2023,Imperial College London,3752487.47,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2018 +C00402,ES/V00381X/1,Supporting fiscal policy decisions in the crisis,"We are going through an economic crisis. The government has responded with an unprecedented policy package, costing many tens of billions of pounds over just a few months - paying for employees to be furloughed, making payments to the self-employed, forgiving business rates, increasing public service spending and making the benefit system much more generous. Over the coming year, the government will have to decide whether to do more to insure households' incomes and prevent business failure, whether to use fiscal policy to kickstart the economy as the health crisis subsides and, ultimately, how to unwind these measures or whether to make some of them permanent. To guide these momentous decisions we propose targeted new analysis of new data sources, including a soon-to-be-available covid-19 module in a large-scale longitudinal household survey and real-time bank account data from a budgeting app. Combined with IFS' world-leading expertise on tax and benefit policy design and unrivalled familiarity with the institutional and policy context around the UK's labour market, taxes and benefits and the public finances, will inform how fiscal policies should be adjusted in the coming 12 months. We are having regular discussions and seminars with civil servants and policy advisors at the top of government through this crisis. The new work proposed here would feed in to this engagement directly, allowing us to help policy-makers take difficult decisions in this highly unusual and fastmoving economic environment, including through taking advantage of novel and timely data sources to produce the best possible empirical evidence.",2020,-99,Institute for Fiscal Studies (IFS),149371.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C00403,ES/V004069/1,Disabled people and COVID-19 in the UK,"Disabled people are vulnerable to health and social impacts of COVID-19. For many, their support needs and their impairments make them more susceptible to the condition and increase the risk of mortality. This qualitative study will explore disabled people's experiences of the epidemic in the short and medium term. It will also document the impact of social isolation and the interruption of support on their wellbeing, the barriers and facilitators of this process and lessons learned for policy and practice. We will conduct 60 in-depth telephone interviews with a range of disabled people, including parents of disabled children, with different conditions, in different social and physical locations across England and Scotland. People will be recruited via disabled people's organisations, social care organisations, parent support groups and voluntary bodies. We will adopt a quota sampling approach to select individuals in each category. We will also interview 15 key informants drawn from these organisations to understand broader experiences of their communities. Interviews for both individuals and key informants will cover impairment-specific health and rehabilitation, general health, social care, everyday life, mental health and isolation, and suggestions for solutions to barriers experienced. After six months, interviews will be repeated to track changes over time, so that we can understand short and medium term impacts. All interviews will be transcribed and we will take an inductive approach and conduct thematic analysis, looking for themes and categories. Findings will be disseminated via disability research and public health research journals and directly to policy-makers. They will also be disseminated to lay publics via broadcast and print media.",2020,-99,London School of Hygiene & Tropical Medicine,353798.09,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C00404,ES/V003909/1,COVID-19: Being alone together: developing fake news immunity,"This project is framed in the area of ""crisis informatics"", the study of how (mis)information about COVID-19 is generated and flows over media platforms. The main goal is that of reverse-engineering the manipulation of information providing citizens with the means to act as fact checkers. We believe that fostering global digital activism constitutes a necessary means to fight the current info-pandemic. The majority of fact-checking and myth-busting sites (e.g. EUvsDisinfo, https://www.who.int/emergencies/diseases/novel-coronavirus- 2019/advice-for-public/myth-busters) counter false narratives and news that have already become viral, unable to prevent their spread. Furthermore, AI techniques (http://www.fakenewschallenge.org) are currently not accurate enough to replace humans in generalised fact-checking. This is especially the case when the news does not contain fabricated information (disinformation), but it is framed in such a way that true evidence is used to draw false generalizations and evaluations (Wardle 2019), resulting in semi-fake news. Leveraging NLP techniques for topic modelling and frame analysis (Das et al. 2010) we will trace the topics and frames which characterize semi-fake COVID-19 news using FullFact (https://fullfact.org/) and the Coronavirus debunking archive built by First Draft (https://firstdraftnews.org/long-form-article/coronavirus-resources-for-reporters/) as benchmarks. We will identify the fallacious reasonings in the sample and use the results to compile a set of guidelines about how to detect semi-fake COVID-19 news. These principles will be operationalised in a digital platform with a chatbot for training citizens to spot misinformation. Citizens who have been trained will have access to the Fake News Immunity platform, working together with experts in the common effort of flagging semi-fake news.",2020,-99,University of Liverpool,258883.5,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C00405,ES/V00400X/1,COVID-19: Monitoring the effects of the pandemic on illicit online trade,"The pandemic has reshaped the demand for goods and services worldwide. Economic stress, the public health emergency and disinformation-driven panic have pushed customers, and vendors, towards the shadow economy. In particular, Dark web marketplaces (DWMs), commercial websites easily accessible via free software like Tor, have acquired significant popularity. They accept Bitcoin and other cryptocurrencies to broker transactions often involving drugs, weapons, and other illicit goods. UK presence on DWMs is strong: As of April 6, 86% of COVID-19 related listings on DWMs would ship to UK and 45% were shipped from UK. This project will build an infrastructure to monitor dark web trading in COVID-19-related goods and services. First, we will monitor listings on DWMs to detect changes in types and prices of COVID-19-related goods and services (e.g., face masks, prescription drugs, scams). Second, we will analyse patterns of Bitcoin (or other cryptocurrency) transactions involving DWMs and their users to quantify policy-relevant changes in trading activity patterns and customer behaviour. The rapid evolution of the pandemic requires gathering and analysing critical data quickly, and a strong research effort to improve the current understanding of DWMs. Our interdisciplinary research team is perfectly equipped for this challenge. Live results shared in reports and a dedicate website will (i) uncover market demand and supply of critical goods and services, (ii) support policymakers' plans for their provision and (iii) assist and complement the UK's effort to combat disinformation about coronavirus, scams, and to counter panic-buying of counterfeit goods that could threat public health.",2020,2021,City University of London,267793.98,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Other secondary impacts,2020 +C00406,ES/V003917/1,COVID-19: Outreach to Domestic Abuse Victims in Times of Quarantine,"Police reports suggest that domestic abuse (DA) has risen as a result of the pandemic, yet there is concern that the share of DA incidents reported may have fallen. When a victim and abuser are quarantined together, calling the police may jeopardize the victim's safety. As a result, greater numbers of victims are increasingly isolated and at risk. So how can victims get help? How can authorities let them know what options are available? Direct messaging can be dangerous, since texts from the police may provoke a controlling abuser. We propose a targeted social media campaign to inform potential high-risk victims about the Silent Solution, a safer option for contacting police. Our approach leverages the wide use of social media, which also poses less risk than direct messaging. Whereas text messages are actively sent, social media adverts are passively received. The study will identify potential high-risk victims and randomly select half for the media campaign. Analysis of DA calls will show whether the approach is effective. If so, it will provide an approach for reaching isolated DA victims, and for giving them options to get help, that will be of value both during quarantine and beyond.",2020,-99,London School of Economics and Political Science,192969.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C00407,ES/V004085/1,"The effects of social distancing policies on children's language development, sleep and executive functions.","The environments children grow up in heavily influence key elements of cognitive development such as language and executive functions, which in turn associate with later educational and occupational attainment as well as health and wellbeing (1-8). The COVID-19 pandemic is a unique, once-in-a-lifetime situation that has dramatically changed the daily lives of millions of families. Several environmental factors likely to be affected by quarantine measures (such as sleep (9-17), parenting style and social interactions (18-22), screen use (23-27), and outdoor activities/exercise (28)) are known predictors of language and executive function development. The proposed study will follow up a UK-wide cohort of 600 children aged 8 to 36 months of age, enrolled in an online study at the onset of social distancing measures, to capture changes in key environmental variables and measure their impact on children's vocabulary size and executive function. Using sophisticated analyses on a large and diverse sample, we will examine the role of each factor on children's cognitive abilities. At this time of unforeseen and ongoing change, it is imperative to understand the impacts of the lockdown on cognition during a critical period for development (0 to 3 years of age), and then find strategies to minimise disruption to this cohort. Our findings will identify approaches that mitigate the temporary loss of formal early years' education, identify those groups most at risk of adverse consequences, and inform policy on how to remediate the negative impacts of lockdown post-COVID-19.",2020,-99,Oxford Brookes University,256758.34,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C00408,ES/V003976/2,Where does work belong anymore? The impact of the COVID19 pandemic on working in the UK,"The COVID-19 outbreak has forced companies to embrace home-based working (HBW) at such speed that they have had little opportunity to consider the impact on their workers. It can be argued that the crisis has led to the most significant, intensive social experiment of digital, HBW that has ever occurred. The current situation, which involves the whole household being based at home, is an unprecedented challenge which may be at least an intermittent fixture, for the next eighteen months (BBC Futures, 25/03/20). The press have suggested that this revolution ""might also offer an opportunity for many companies to finally build a culture that allows long-overdue work flexibility ...many employees for companies who have sent all staff home are already starting to question why they had to go into the office in the first place"" (The Guardian, 13/02/20). These optimistic takes on the current patterns of work focus on HBW's emancipatory potential, offering flexibility, the lubrication of work and family responsibilities and the promise of increased productivity. Yet, this new world order, where the home becomes a multi-occupational, multi-person workplace and school, not only challenges boundaries but also conceptions of the domestic space. The impact of homeworking is likely to present significant variation depending on organisational support, the worker's role, socio-economic status, employment status, as well as household composition and size of living space. There are significant concerns regarding intensified HBW, including poor work-life balance, enhanced domestic tensions and disproportionately negative impacts on those in lower socio-economic groupings. Moreover, HBW increases the proportion of time women (most often) spend on housework and childcare, reproducing and reinforcing gender roles within the new 'work-space' We will examine in-depth this radical shift in working arrangements and how it impacts on the wellbeing and productivity of workers and their households. Using a combination of in-depth interviews with sixty participants, representing the spectrum of this novel group of homeworkers, as well as a large-scale survey, this project (Working@Home) will provide unrivalled insights into the experience of home-working for the UK population and will serve as a permanent record of the lives of citizens in this unprecedented time. The research will be key in understanding the expectations that organisations have placed on workers, as well as the robustness of support systems that have been put in place, taking into account the rapid advancement of home working systems with almost no preparation and only limited existing support structures or expertise. The findings will provide a benchmark for the resilience of both individuals and businesses and demonstrate the potential for the robustness of the infrastructure in the return to a 'new normal' after the crisis. In order to ensure that the findings from the project are accessible to all, we are developing a website (workingathome.org.uk) that will host up to date information on the progress of the project, details of the project team, guidance for participants as well as information regarding our webinar series. The project aims to produce guidance to individuals, organisations and policy makers on how to best manage the ongoing medical emergency from a home-working perspective as well as providing guidance for any future pandemic scenario.",2020,-99,Newcastle University,273105.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C00409,ES/V004034/1,"COVID-19: Supporting Parents, Adolescents and Children during Epidemics (Co-SPACE)","COVID-19 and the related public health measures have led to major disruptions to families' lives, with different pressures arising for children, young people and their families over time. There is some indication from research during epidemics in other countries of a negative impact on children and young people's mental health but this comes from small, cross-sectional studies with limited generalisability to the current context in the UK. The Co-SPACE project aims to track children and young people's mental health throughout the COVID-19 crisis through an online longitudinal survey completed monthly throughout the pandemic by parents/carers of children aged 2-16 years and young people themselves (if aged 11-16 years). We will specifically track young people from vulnerable groups, such as those from low income households, with preexisting mental/physical health difficulties and looked after children. To complement this and develop a richer understanding in-depth, qualitative interviews will be conducted with parents/carers, young people and people who work with them. Study materials have been shared with international collaborators in over 15 countries (including Germany, China, Japan, USA, Canada, Iran) and data will be linked to explore how patterns associated with youth mental health vary across contexts. The findings will help us identify what protects children and young people from deteriorating mental health over time, what support families need, and how this may vary according to contexts.",2020,-99,University of Oxford,350426.29,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C00410,ES/V004018/1,Food System Impacts of COVID-19,"This research will examine the extent of continuity and dislocation in the supply chain across dairy products, meat, fresh fruit and vegetables, and fish. They will look at instances of radical changes in routes to markets and the barriers to change; the experiences of primary producers as supply chains adapt and change; the regulations, incentives, investments or interventions which might be required to optimise supply chain adjustments and ensure fairness; and long term implications of the crisis for the food supply chain. They will establish a panel of experts from each of the four main food sectors (dairy, meat, fruit & veg and fish) to confer fortnightly. They will conduct on-line research on supply chain issues and concerns, an on-line survey, and conduct c50 key telephone interviews with producers, processors, distributors and retailers. Their work will be interactive and iterative, with findings communicated through monthly bulletins, 'living documents' updatable by stakeholders and a project website.",2020,-99,University of Exeter,221675.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C00411,ES/V004026/1,"How to understand, scale and maximise the effectiveness of volunteer responses to COVID-19.","COVID-19 necessitates 'self-isolation and social distancing' to 'keep people safe'. This requires radically different ways of meeting essential needs in food supply, healthcare and wellbeing. At the same time, existing needs such as food poverty, homelessness and unemployment have been exacerbated. The UK government has mobilised a new army of volunteers on an unprecedented scale to meet these needs (Gov.UK, 2020). This offers a potentially huge resource to the Voluntary and Community Sector (VCS) and to Local Authorities (LAs), however, it also presents significant challenges around how to deploy and optimize volunteer support. This proposed project will address the knowledge gap around what community resource mobilisation, infrastructural support and capacity building is required to organise the scale and pace of volunteering needed in a restricted environment, and share good practice to maximise responses to COVID-19. It will do so by enabling the nationwide sharing of innovations and good practices between LAs and VCS organisations charged with managing volunteer responses. It will collate, distil and disseminate the learning from organisations (national, local and micro), creating a national picture of what strategies are being utilised and corresponding stress points. The research team draws on its significant experience of volunteering and of working in partnership with LAs and VCS organisations through the Enabling Social Action Programme (ESA) (2018-2020), which we run for the department of Digital, Culture, Media and Sport (DCMS). The trusted cross-sectoral relationships and experiences of sharing practices and learning embedded in ESA provides a framework for this project.",2020,-99,University of Sheffield,467559.39,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Community engagement | Systemic/environmental components of capacity strengthening, +C00819,01KI20140A,HUman Lung model for Key screens and preclinical validation of antivirals against SARS-CoV-2 infection,"Abstract: ""Rapid screens of potential antivirals are urgently needed to mitigate the current COVID-19 outbreaks. Ideally, such screens should be deployed in models that closely reflect the biologically and clinically relevant environment of the virus infection, because this may accelerate the discovery of promising drug candidates. We propose to develop an in vitro model of human lung infection with SARS-CoV-2 infection for initial screening and in depth validation of hits. Our laboratories possess strong virological expertise, including direct work with SARS-CoV-2. We have established cultures of human respiratory epithelial cells in monolayers or in 3D models of culture at air/liquid interfaces. The SME partner has established a technology for the development of immortalized cell lines and has been expanding stocks of cells from upper and lower parts of the respiratory system. We propose to combine these models to develop (1) direct screens of antiviral compounds in 2D cultures of human respiratory cells and (2) validation assays in 3D models.""; Research Type: discovery; Study population: not applicable",2020,2021,"Helmholtz Zentrum für Infektionsforschung, Braunschweig",136398.23,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +C00820,01KI20140B,HUman Lung model for Key screens and preclinical validation of antivirals against SARS-CoV-2 infection,"Abstract: ""Rapid screens of potential antivirals are urgently needed to mitigate the current COVID-19 outbreaks. Ideally, such screens should be deployed in models that closely reflect the biologically and clinically relevant environment of the virus infection, because this may accelerate the discovery of promising drug candidates. We propose to develop an in vitro model of human lung infection with SARS-CoV-2 infection for initial screening and in depth validation of hits. Our laboratories possess strong virological expertise, including direct work with SARS-CoV-2. We have established cultures of human respiratory epithelial cells in monolayers or in 3D models of culture at air/liquid interfaces. The SME partner has established a technology for the development of immortalized cell lines and has been expanding stocks of cells from upper and lower parts of the respiratory system. We propose to combine these models to develop (1) direct screens of antiviral compounds in 2D cultures of human respiratory cells and (2) validation assays in 3D models.""; Research Type: discovery; Study population: not applicable",2020,2021,"InSCREENeX GmbH, Braunschweig",76671.02,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +C00821,01KI20150A,Identifying host factors as drug targets and drugs employing RNAi knockdown screens,"Abstract: We aim to identify and effectively inhibit host dependency factors being essential for SARS-CoV-2 replication and spread, following a systematic screening approach. Human epithelial cells will be seeded in ""ready to transfect"" multiwell plates, designed and produced in the laboratory of HE. Those plates are containing dried siRNA/transfection reagent complexes. When the cells attach to the surface, reverse transfection enables siRNA mediated knockdown of a single gene, in high-throughput. Then, the cells will be infected with clinical SARS-CoV-2 isolates collected by SC and cCytopathic effect and MTT assays performed. After inactivation by paraformaldehyde, these transportable plates will be sent to the lab of HE who will elaborately phenotype the cells using an established imaging pipeline. RK will compare the hits from the screen to time-lapse proteomics data of SARS-CoV-2 infected human epithelial host cells (data was derived from SC recently), omics data from other coronavirus infection studies, and gene associations to the Severe Acute Respiratory Syndrome. This will lead to a short list of host dependency factors for which drugs will be selected employing publicly available drug databases. Selected host factors and drugs will be validated in the lab of SC employing a broad selection of SARS-CoV-2 isolates. In addition, RK will infer a SARS-CoV-2 specific protein interaction network and identify clusters of host factors to get drug combinations, which will be experimentally validated by SC. We will yield an effective drug treatment for COVID-19 therapy and prevention.; Research Type: discovery; Study population: not applicable",2020,2021,Jena University Hospital,146852.09,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00822,01KI20150B,Identifying host factors as drug targets and drugs employing RNAi knockdown screens,"Abstract: We aim to identify and effectively inhibit host dependency factors being essential for SARS-CoV-2 replication and spread, following a systematic screening approach. Human epithelial cells will be seeded in ""ready to transfect"" multiwell plates, designed and produced in the laboratory of HE. Those plates are containing dried siRNA/transfection reagent complexes. When the cells attach to the surface, reverse transfection enables siRNA mediated knockdown of a single gene, in high-throughput. Then, the cells will be infected with clinical SARS-CoV-2 isolates collected by SC and cCytopathic effect and MTT assays performed. After inactivation by paraformaldehyde, these transportable plates will be sent to the lab of HE who will elaborately phenotype the cells using an established imaging pipeline. RK will compare the hits from the screen to time-lapse proteomics data of SARS-CoV-2 infected human epithelial host cells (data was derived from SC recently), omics data from other coronavirus infection studies, and gene associations to the Severe Acute Respiratory Syndrome. This will lead to a short list of host dependency factors for which drugs will be selected employing publicly available drug databases. Selected host factors and drugs will be validated in the lab of SC employing a broad selection of SARS-CoV-2 isolates. In addition, RK will infer a SARS-CoV-2 specific protein interaction network and identify clusters of host factors to get drug combinations, which will be experimentally validated by SC. We will yield an effective drug treatment for COVID-19 therapy and prevention.; Research Type: discovery; Study population: not applicable",2020,2021,Johann Wolfgang Goethe-Universität Frankfurt am Main,233904.42,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00823,01KI20168,The effects of commonly used drugs on the alveolar homeostasis during SARS-CoV-2 infection,"Abstract: ""The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causes besides asymptomatic courses, in many cases severe progression including pneumonia with high mortality rates. Up to now, no vaccines or efficient therapeutic strategies are available. Many clinical approaches focus on repurposing of approved therapeutics against other diseases. However, efficacy of these compounds on viral infection or even harmful secondary effects in context of SARS-CoV-2 infection is sparsely investigated. Similarly, adverse events of commonly used therapeutics against lifestyle diseases are unknown. Major problems correlated to COVID-19 are lung tissue damage, dysregulation of the innate immune response and abnormal coagulation parameters. To investigate processes that maintain lung homeostasis, we have established a human alveolus-on-a-chip model, which is composed of epithelial-cells and endothelial-cells as well as macrophages. By use of this system, the alveolar homeostasis, which is easily dysbalanced by infections, can be examined. We will investigate (a) the replication efficacy of SARS-CoV-2 isolates in epithelial and endothelial cells, (b) the effects of infection on innate immune response (c) the barrier integrity and regulation of vascular coagulation and fibrinolysis system and (d) the effects of commonly used therapeutics on SARS-CoV-2 infection that also act on the vascular system. We expect complex insights into the pathophysiology of SARS-CoV-2 infection on the different cell types that are involved in the disease development.""; Research Type: discovery; Study population: not applicable",2020,2021,Jena University Hospital,298112.01,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C00824,01KI20169A,Targeting invasion strategy of SARS-CoV-2 in bronchial epithelial cells,"Abstract: ""COVID19 is caused by the infection of airway epithelial cells and causes severe respiratory collapse that escalates in an overactivation of the immune system. Objectives: To identify the cellular mechanisms in primary epithelial cells in response to SARS-Cov2, the regulation of ACE2, pattern recognition receptors and host defense mechanisms. Further, to investigate the effect of IFN-g and IL-4 on epithelial infection and understand, which epithelial differentiation stages are susceptible to SARS-Cov2. Furthermore, we will investigate the role of potential therapeutic options to inhibit IFN-?-induced ACE2 expression using specific inhibitors for bradykinin-b2 receptor (Icatibant;HOE140), JAK/STAT-pathway (Tofacitinib), FoxO1 (AS1842856), as the ACE2 promoter contains IRF2 and FOXO1 binding sites.Preliminary Results: Primary human epithelial cells can differentiate into type-1 and type-2 epithelial cells affecting large proportions of the functional portfolio. We propose to identify the Sars-Cov2 secretion profile triggered in E1-differentiated cells, which could be used for home-care diagnostic kits, even if the viral origin is unknown. We discovered that ACE2, the SARS-Cov2 entry receptor is strongly up-regulated in the E1 cells. Furthermore, ACE2 protein was found to be higher in E1 cells, while Icatibant, a licensed drug, inhibits ACE2 up-regulation in E1 cells.Outlook: The proposed project sheds light epithelial immune response triggered by SARS-Cov2 in context of the E1 differentiation pathway and offers novel solutions for diagnosis and therapy.""; Research Type: discovery; Study population: not applicable",2020,2021,Technische Universität München,325081.99,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00825,01KI20169B,Targeting invasion strategy of SARS-CoV-2 in bronchial epithelial cells,"Abstract: ""COVID19 is caused by the infection of airway epithelial cells and causes severe respiratory collapse that escalates in an overactivation of the immune system. Objectives: To identify the cellular mechanisms in primary epithelial cells in response to SARS-Cov2, the regulation of ACE2, pattern recognition receptors and host defense mechanisms. Further, to investigate the effect of IFN-g and IL-4 on epithelial infection and understand, which epithelial differentiation stages are susceptible to SARS-Cov2. Furthermore, we will investigate the role of potential therapeutic options to inhibit IFN-?-induced ACE2 expression using specific inhibitors for bradykinin-b2 receptor (Icatibant;HOE140), JAK/STAT-pathway (Tofacitinib), FoxO1 (AS1842856), as the ACE2 promoter contains IRF2 and FOXO1 binding sites.Preliminary Results: Primary human epithelial cells can differentiate into type-1 and type-2 epithelial cells affecting large proportions of the functional portfolio. We propose to identify the Sars-Cov2 secretion profile triggered in E1-differentiated cells, which could be used for home-care diagnostic kits, even if the viral origin is unknown. We discovered that ACE2, the SARS-Cov2 entry receptor is strongly up-regulated in the E1 cells. Furthermore, ACE2 protein was found to be higher in E1 cells, while Icatibant, a licensed drug, inhibits ACE2 up-regulation in E1 cells.Outlook: The proposed project sheds light epithelial immune response triggered by SARS-Cov2 in context of the E1 differentiation pathway and offers novel solutions for diagnosis and therapy.""; Research Type: discovery; Study population: not applicable",2020,2021,"Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg",219935.98,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00826,01KI20173,Seroconversion rate to SARS- CoV-2 in an unselected cohort of children and mothers in certain region of North-Rhine-Westphalia (Ruhrgebiet),"Abstract: ""Data on SARS-CoV-2/COVID-19 in children (until 18 years of age) is limited. Probably most of the infected children remain undetected due to the lack of clinical symptoms. The rate of seroconversion can be assessed by measuring SARS-CoV-2 IgA and IgG antibodies 2-4 weeks after the infection.The aim is to estimate the rate of seroconversion to SARS- CoV-2 in a large and unselected sample of asymptomatic children at defined time points (screening examinations in outpatient practices) in an urban region of North-Rhine-Westphalia. Symptoms and history of COVID-19 symptoms will be assessed and IgA and IgG antibodies measured. Possible risk factors for SARS- CoV-2 infection from the patient's history (e.g. co-morbidity, smoking exposure, social aspects etc.) will be detected. Frequency of infections and pulmonary symptoms in seropositive/negative children symptoms during the one year follow- up are recorded. Additionally, the rate of seroconversion in mother-child pairs (concordant vs discordant) will be evaluated in order to estimate the risk of exposure. Variations in ACE2 and TMPRSS2 will be measured since angiotensin I converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2) l seem to play a crucial role for SARS-CoV-2 entry into host cells. Since different expression of these receptors could explain the differences in severity of COVID-19 infection in children vs. adults, a subgroup of children and mothers will be selected for later RNA analyses in nasal and oral mucosae.""; Research Type: epidemiological study; Study population: children and adolescents",2020,2021,Ruhr- Universität Bochum,613512.14,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C00827,01KI2045,Preclinical development of SARS-CoV-2 helicase and macrodomain inhibitors - Targeting unique mechanisms for COVID-19 therapy,"Abstract: ""Eisbach has identified and validated small molecule drugs that target disease-relevant and novel mechanisms in SARS-CoV-2. Using an allosteric HTS and in vivo platform, we identified ~300 helicase inhibitors and ~60 inhibitors targeting the ADP-ribose-binding macrodomain of ALC1/CHD1L, an oncogene. We observe high sequence/structure conservation with the SARS-CoV-2 helicase and Nsp3 X-domain macrodomain mono-ADP-ribosylhyrolase, enzymes for which we have pioneering, worldwide expertise. Since the viral helicase and one of the macrodomains of SARS-CoV-2 are essential for viral replication and to suppress the host's immune system, they represent novel, highly promising drug targets. Our AI-supported molecular docking algorithm validated a binding pocket in the helicase, in particular. The 87 cell-permeable, drug-like and cell-active inhibitors that we have profiled are predicted to be high nanomolar SARS-CoV-2 blockers, have been profiled for toxicity, physchem properties and in silico ADMET. This will enable rapid lead optimization. The objectives of our grant are to develop a pre-clinical proof-of-concept for small molecule inhibitors toward the treatment of COVID-19 and other, future CoV infections. Our rationale for validating these novel inhibitors toward helicase and macrodomain ADP-ribosyl hydrolase enzymes of SARS-CoV-2 lies in the novelty of our targets, the orthogonal approach we have taken to identify small molecule inhibitors that target the helicase outside of its canonical ATP binding pocket and the specific coronavirus functions that our drugs disrupt.""; Research Type: discovery; Study population: not applicable",2020,2021,"Eisbach GmbH, Martinsried",1299288.54,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00828,01KI2058,Analysis of SARS-CoV-2 infection in human lung organoids,"Abstract: ""Organoids are three dimensional tissues derived from stem cells. The usage of human induced pluripotent stem cells (iPSC) enables the differentiation into organoids with human tissue-like features. iPSC can also be used to differentiate human lung organoids (HLO). The organization of HLOs is similar to the native lung, e.g. these organoids contain upper airway-like epithelium with basal cells, immature ciliated cells, smooth muscle, myofibroblasts as well as alveolar-like cell types. Thus, HLOs offer an excellent model to study human lung diseases like COVID-19. Moreover, the iPS derived organoids overcome several of the limitations of currently used biopsy lung derived models (availability of alveolar epithelial type II cells (AT2), inter biopsy variance).Within this proposal we aim to elaborate basics for the establishment of a high-throughput approach (differentiate HLOs with low variance). HLOs will be characterized using cryo-sectioning and immunofluorescence analysis upon SARS-CoV-2 infection. We aim to study viral replication kinetics and host responses. We recently contributed to the establishment of the first reverse genetics system for SARS-CoV-2 offering the flexibility of using reporter viruses for a screening approach. Finally, we will test our system upon treatment with established antiviral compounds and aim to set up screening approaches to test antiviral compound libraries. Our approach offers a state-of-the-art model to study SARS-CoV-2 derived pathology and paves the way for the identification of effective antiviral drugs at high throughput level.""; Research Type: discovery; Study population: not applicable",2020,2021,Ruhr Universität Bochum,423607.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Disease pathogenesis,2020 +C00829,01KI2060,Development of an on-site rapid test for the detection of SARS-CoV-2 antigenes for the Charité Berlin,"Abstract: The aim of the project is to prepare an on-site rapid test for the specific detection of SARS-CoV-2 based on the preparatory work of the project ""SARS-MAB - Generation of murine, monoclonal antibodies against SARS-CoV-2"" (UPK GmbH). Developed patient samples will be made available to Charité (AG Dr. Corman).The planned test procedure can form the basis for further research into the virus and the course of the disease and could possibly also be used in diagnostic procedures.; Research Type: discovery; Study population: not applicable",2020,2021,"Fassisi mbH, Göttingen",31959.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C00830,01KI2071,Covid-19 - Evaluation of prevention strategies by agent-based simulations,"Abstract: The aim of the project is to use specific simulations to investigate the outbreak of SARS-CoV-2 and the influence of containment measures. If successful, the project can provide significant help in dealing with the pandemic, both in medical, social and, if necessary, economic terms. The project builds on a BMBF-funded project (01KI1913) for pathogen-specific modeling of other (potential) epidemics. Accordingly, the preparatory work and cooperation established there can be used.; Research Type: discovery; Study population: not applicable",2020,2021,Westfälische Wilhelms-Universität Münster,64964.43,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Impact/ effectiveness of control measures,2020 +C00831,01KI2072A,Therapeutic expansion of protective effector and memory T-cell responses against SARS-CoV-2,"Abstract: ""T cells destroy virus-infected host cells and regulate the production of virus-neutralizing antibodies to prevent the virus from entering the cell and multiplying. To instruct T cells viral components must be presented by MHC molecules alongside costimulatory molecules on antigen-presenting cells. MHC molecules show a high degree of variation across the population and the distribution of these variants (allotypes) vary significantly between individuals and ethnicities. Thus, T cell responses are significantly tailored by the combination of an MHC allotype and the presented viral peptide. Recombinantly expressed MHC allotypes will be loaded with in silico predicted and verified viral peptides. Using these sets together with newly discovered costimulatory molecules for T cells will enable us to expand and visualize specific T-cell responses of small subpopulations. The novel approach will be used to characterize the T-cell responses of recovered SARS-CoV-2-infected individuals to determine their effector and memory response which mediated protection/cure. Results will be compared to T-cell responses of COVID-19 patients in the first phase of the disease for prediction of disease outcome. In perspective, the novel approach can also be utilized to expand and manipulate SARS-CoV-2-specific T-cell responses as cellular therapy for COVID-19 patients. Our results will provide novel insights into the mechanisms of cellular adaptive immune responses against the still largely unknown SARS-CoV-2 virus, which could form a basis for diagnosis and future therapy of this infection.""; Research Type: discovery; Study population: not applicable",2020,2021,Otto-von-Guericke Universität Magdeburg Freie Universität Berlin,299548.81,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C00832,01KI2072B,Therapeutic expansion of protective effector and memory T-cell responses against SARS-CoV-2,"Abstract: ""T cells destroy virus-infected host cells and regulate the production of virus-neutralizing antibodies to prevent the virus from entering the cell and multiplying. To instruct T cells viral components must be presented by MHC molecules alongside costimulatory molecules on antigen-presenting cells. MHC molecules show a high degree of variation across the population and the distribution of these variants (allotypes) vary significantly between individuals and ethnicities. Thus, T cell responses are significantly tailored by the combination of an MHC allotype and the presented viral peptide. Recombinantly expressed MHC allotypes will be loaded with in silico predicted and verified viral peptides. Using these sets together with newly discovered costimulatory molecules for T cells will enable us to expand and visualize specific T-cell responses of small subpopulations. The novel approach will be used to characterize the T-cell responses of recovered SARS-CoV-2-infected individuals to determine their effector and memory response which mediated protection/cure. Results will be compared to T-cell responses of COVID-19 patients in the first phase of the disease for prediction of disease outcome. In perspective, the novel approach can also be utilized to expand and manipulate SARS-CoV-2-specific T-cell responses as cellular therapy for COVID-19 patients. Our results will provide novel insights into the mechanisms of cellular adaptive immune responses against the still largely unknown SARS-CoV-2 virus, which could form a basis for diagnosis and future therapy of this infection.""; Research Type: discovery; Study population: T-cell analysis for healthy individuals, patients infected with COVID-19 and recovered individuals after COVID-19 infection",2020,2021,Freie Universität Berlin,297242.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C00833,01KI2074A,Domestic animals as potential vectors for SARS-CoV-2 transmission,"Abstract: ""The recent emergence and the rapid pandemic spread of SARS-CoV-2 pose a global health emergency. The origin of the virus has not been fully investigated so far. It is assumed that horseshoe bats harboring progeny coronaviruses serve as the natural reservoir host, while pangolins may serve as intermediate host. However, information on potential permissive animal species is largely lacking. Given the frequent and close contact between humans and domestic animals, is it important to elucidate whether animals such as dogs, cats or ferrets and livestock, especially cattle and pigs, are susceptible to SARS-CoV-2 infection and might promote viral dissemination among animals and humans. Indeed, there is already circumstantial evidence that dogs might become infected by SARS-CoV-2. Therefore, this project will employ primary cells obtained from the upper and lower respiratory tract of a variety of domestic animals to determine permissiveness to SARS-CoV-2 infection. Studies will include mode of entry and spread and pathogenetic mechanisms using molecular and microscopic analyses. The results will facilitate risk assessment and prevention of potential interspecies transmission.""; Research Type: discovery; Study population: domestic animals (cats, dogs) and farm animals (bovine animals, pigs)",2020,2021,"Deutsches Primaten Zentrum, Göttingen",89256.79,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +C00834,01KI2074B,Domestic animals as potential vectors for SARS-CoV-2 transmission,"Abstract: ""The recent emergence and the rapid pandemic spread of SARS-CoV-2 pose a global health emergency. The origin of the virus has not been fully investigated so far. It is assumed that horseshoe bats harboring progeny coronaviruses serve as the natural reservoir host, while pangolins may serve as intermediate host. However, information on potential permissive animal species is largely lacking. Given the frequent and close contact between humans and domestic animals, is it important to elucidate whether animals such as dogs, cats or ferrets and livestock, especially cattle and pigs, are susceptible to SARS-CoV-2 infection and might promote viral dissemination among animals and humans. Indeed, there is already circumstantial evidence that dogs might become infected by SARS-CoV-2. Therefore, this project will employ primary cells obtained from the upper and lower respiratory tract of a variety of domestic animals to determine permissiveness to SARS-CoV-2 infection. Studies will include mode of entry and spread and pathogenetic mechanisms using molecular and microscopic analyses. The results will facilitate risk assessment and prevention of potential interspecies transmission.""; Research Type: discovery; Study population: domestic animals (cats, dogs) and farm animals (bovine animals, pigs)",2020,2021,Stiftung Tierärztliche Hochschule Hannover,109423.92,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +C00835,01KI2082,Human alveolar barrier damage in COVID 19 associated lung failure,"Abstract: The aim of the project is to investigate whether the body's own substances are responsible for the damage to the lung tissue in COVID-19 patients who suffer from the so-called ""Acute Respiratory Distress Syndrome"" (ARDS). The investigation is to be carried out in the laboratory on lung cells. In addition, the aim is to investigate whether the suspected mechanism of action that triggers ARDS can be inhibited by an active ingredient that has already been tested in clinical studies for other indications. In the short to medium term, such studies could provide important insights for the treatment of severe cases of COVID-19. If the project is successful, a starting point for the development of a therapeutic agent could be identified in the medium to long term.; Research Type: discovery; Study population: not applicable",2020,2021,Charité - Universitätsmedizin Berlin,54137.02,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Disease pathogenesis,2020 +C00836,01KI2091,Risk Communication Requirements for Special Target Groups in a Long Lasting COVID-19-Ccrisis,"Abstract: Challenges to risk communication in the Sars-CoV-2 pandemie will increase over time.Special forms of communication, both in terms of contents and modes, have to be developed for different target groups: Older people are more vulnerable to severe variants of the illness, younger people, by remaining mobile when infected and tending to be less compliant to rules of social distancing, might play a larger role in spreading the virus. This study will explore the major risk perceptions and behavioral intentions of different target groups. Communication methods and formats will be designed that promise to foster adequate behavior thus leading to risk reduction. The chain from risk perception, awareness, willingness to act up to behavioral change will inform the analysis. The risk perception paradox describing the gap between risk perception and protective action, can be addressed by identifying the opportunities of and barriers to risk adaptive behavior and enabling target-specific and inclusive risk communication. A long-term COVID-19- risk communication program will be established that is still effective when the peak of the crisis has been passed but protective action is still needed.The project will use survey methods in conjunction with focus groups and consensus methods (e.g. Group Delphi). This study will aim at providing a long-term risk communication manual, based on empirical and risk communication experience and a consensus among communication experts. Effective communication will reduce risks to health and live and can contribute to a better health record.; Research Type: social sciences; Study population: individuals of two age groups, 18-30 years of age and 50-70 years of age",2020,2021,"DIALOGIK gemeinnützige Gesellschaft für Kommunikations- und Kooperationsforschung mbH, Stuttgart",243550.55,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2020 +C00837,01KI2097,Public health protection through civil and disaster protection in pandemic situations using the example of SARS-CoV-2,"Abstract: The aim of the project is to analyze the role of civil and civil protection organizations in supporting the public health service (ÖGD) in the corona pandemic. The legal, administrative and socio-historical background of public health protection in the exemplary pandemic is examined and the corresponding interfaces are highlighted. In cooperation with partners from civil and civil protection, the current state is recorded in interviews and the functionality of civil and civil protection under pandemic conditions is discussed. How is the cooperation between the various departments coordinated? How are the volunteers often trained and protected against infections? Potentials and limitations are analyzed and compared internationally. The project complements an ongoing study (WAKE, FKZ 13N14748), which deals with migration-related knowledge management for civil protection using the example of the refugee situation 2015/2016. The planned work should lead to recommendations for action by the public health service.; Research Type: social sciences; Study population: impact on civil and civil protection services",2020,2021,Freie Universität Berlin,52169.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Health Systems Research,Health leadership and governance,2020 +C00838,01KI2099,The COVID-19 Crisis and its impact on the German ambulatory sector - the physicians view,"Abstract: The COVID-19 crisis not only has an impact on the inpatient sector of care but also on general practitioners and specialists in private practice, who provide the majority of general outpatient and specialist medical care in Germany. In addition to the acute consequences for the quality of care, long-term consequences for patients and care providers are to be expected because of the COVID-19 crisis. To learn more about the current situation, as well as the expected and actual long-term consequences, general practitioners and specialists will be surveyed throughout Germany as part of the study. For this purpose, a random selection of general practitioners (n = 5,000), internists (n = 3,000), ENT specialists (n = 2,000), pediatricians (n = 3,000), gynecologists (n = 2,000), and dentists (n = 4,000) will be surveyed anonymously using an online questionnaire. At the same time, the questionnaire offers the possibility to give extensive free text answers, which are analyzed qualitatively to form the basis of the next surveys. The online surveys will be conducted as trend analyses (3 cross-sectional analyses) after 2, 5, and 13 months. Differences according to urban-rural areas (degree of spatial aggregation), age and gender, medical specialization, and organizational form of the practice (community health center (MVZ), shared practice, or group practice) will be analyzed, and statistical group comparisons will be carried out. The aim is to find out which specialist groups are burdened to what extent and what effects are expected for the future.; Research Type: social sciences; Study population: general practitioners",2020,2021,Uniklinik Köln,161185.41,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Dentists and dental staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Gender,,,Germany,Germany,"Secondary impacts of disease, response & control measures | Health Systems Research",Health workforce,2020 +C00839,NE/V004883/1,Use of wastewater analysis to evaluate the incidence of coronavirus (SARS-CoV-2) in the UK population,"The emergence of the novel coronavirus strain SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is now viewed as a major global threat to human health. Recent estimates predict the deaths of 15 million people worldwide and that SARS-CoV-2 infections are likely to result in an economic loss £2.1 trillion GDP. Effective monitoring of this pathogen is vital to estimate the amount of infection circulating in the human population, and to inform the design of measures for controlling the spread of disease. The number of hospitalization cases from SARS-CoV-2 related diseases (COVID-19) provides some measure of disease prevalence in the population, it provides no reliable information on mild infections and asymptomatic carriers. The use of random 'spot checks' and thermal imaging cameras have been introduced to screen for infections, though these are costly to implement and very imprecise. Consequently, better methods are needed to evaluate SARS-CoV-2 prevalence in the wider population. As SARS-CoV-2 is shed in faeces in high amounts (Xiao et al., 2020, Zhang et al., 2020), we hypothesize that wastewater can provide a powerful indicator of disease incidence at any point in time (Ye et al., 2016), particularly as most UK urban centres are served by only 1 or 2 wastewater treatment works, thereby providing a single integrated signal of millions of people in a single sample. The aim of this NERC Urgency project is therefore to: (1) use wastewater to provide near real-time information on the incidence of SARS-CoV-2 within the UK population; (2) monitor the rise and subsequent decline of SARS-CoV-2 in the UK population, and to compare this to conventional disease reporting metrics (e.g. confirmed SARS-CoV-2 hospitalization cases); (3) identify similarities in the abundance of SARS-CoV-2 in the major urban centres of the UK; (4) demonstrate the use of wastewater for the integrated surveillance of human pathogenic viruses within the human population; (5) provide stakeholders (e.g. national government, NHS, HPA, PHE, PHW, HPS, water companies etc) with critical scientific information and tools to be able to respond and adapt to current and potential future disease epidemics.",2020,2021,Bangor University,64390.08,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C00840,NE/V009028/1,The exposure of urban rodents to the human COVID-19 virus and the potential for viral recombination,"All of us are affected by the COVID-19 pandemic, which is caused by a virus (technically, SARS-CoV-2) that originally jumped from an animal (probably a bat) into a person. Now the virus is spreading person-to-person directly. COVID-19 is a coronavirus, and coronaviruses are very common in wild animals. While each coronavirus typically infects one species of animal, coronaviruses can move between animal species too. So the general idea is that animals are ""reservoirs"" of viruses that sometimes moves into people. Because so many people are getting infected with COVID-19, we think that humans might now be a virus reservoir infecting animals. If this does happen, it's most likely where there are high densities of people and of animals - such as rodents in cities, where large numbers of people and rodents live cheek-by-jowl. This is the idea we want to test. But why does this matter? Different viruses can also mix their genetics (technically, recombine), and so we also wonder if the human COVID-19 does infect rodents, whether it will then recombine with other coronaviruses already in those rodents. There are a lots of 'ifs' in these last few sentences, which is because these are just theories that we have. We now want to see if these theories - these 'ifs' - are correct. To do this we want to catch city-dwelling rats and mice that we'll then screen for the human COVID-19 virus, or close relatives of it.",2020,-99,University of Liverpool,209910.32,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C00841,1OT2OD030195-01,Establish a Public Private Partnership for COVID19 Research,"The Foundation for the National Institutes of Health (FNIH) (www.fnih.org) was chartered by the Congress of theUnited States in 1990 as a not-for-profit 501(c)(3) charitable organization and has been working to facilitategroundbreaking research at the National Institutes of Health (NIH) and worldwide since 1996, creating andmanaging numerous biomedical public-private research partnerships that support the NIH's mission. The FNIHtherefore has extensive experience working with both NIH and the biopharmaceutical industry and deep familiaritywith NIH's people, science, practices, and policies.The FNIH has been asked by Dr. Francis S. Collins, Director of the NIH, to assist the agency in its response to theCOVID-19 crisis. The aim of this collaboration is to accelerate NIH research urgently required to respond to thispublic health threat and to save lives by leveraging private-sector scientific expertise, in-kind assets and financialresources to augment federal efforts.Dr. Collins' request that the FNIH help create a COVID-19 public-private partnership (PPP) to accelerate thedevelopment of therapeutics and vaccines under the Accelerating Medicines Partnership (AMP) is consistent withthe FNIH's own mission and the Congressional statute by which the FNIH was established to support the NIH inits mission and to advance collaboration with biomedical researchers from universities, industry, nonprofitorganizations and other federal agencies, including the US Food and Drug Administration (FDA).AMP is a nimble and powerful public-private partnership that includes the NIH, FNIH, FDA and multiplebiopharmaceutical companies and not-for-profit organizations. Managed by the FNIH, AMP programs bringtogether the resources of the NIH and industry to improve our understanding of disease pathways and facilitatebetter selection of targets for treatment. Multimillion dollar collaborations supported by the private sector throughthe FNIH have been established in four major disease areas: Alzheimer's disease, Type 2 diabetes, RheumatoidArthritis (RA)/Lupus and Parkinson's disease. The FNIH is also preparing to launch an AMP in Schizophrenia inpartnership with the National Institute on Mental Health (NIMH).The overarching goal of the FNIH in this new AMP is to support the NIH in designing and implementing a strategicand coordinated cross-sector approach to end the current COVID-19 pandemic and to manage future such threats.This PPP is now known as ACTIV, the Accelerated COVID-19 Therapeutic Intervention and Vaccine partnership.Notably, most AMP projects start with a Design Phase that takes approximately 9 months to complete in which theFNIH identifies key partners, establishes scientific working and sub-groups, puts in place governance structures,executes contracts and agreements, deploys and trains appropriate staff, and identifies potential sources of funding.The result of the Design Phase is a detailed scientific and business plan for the PPP, which is called theImplementation Plan (sometimes referred to as the White Paper). The resulting Implementation Phase is a multiyeareffort in which the PPP, through management by the FNIH, operationalizes the scientific plan and coordinatesthis work with critical support provided by NIH using its grants and contracts mechanisms.However, given the acute public health threat that has resulted in tens of thousands of COVID-19 deaths, the FNIHresponded immediately to NIH's call to action, redirecting staff from active, fully funded donor-supported programsto begin work on the Design Phase for the proposed PPP even though no financing for the FNIH's work has yetbeen secured. In fact, for the past four weeks, the FNIH staff has been working non-stop on ACTIV, includingnights and weekends, and has already achieved in record time what under normal circumstances would have takenmonths. This redeployment of staff is not sustainable, and the resulting costs and lost revenue are imposing anunacceptable burden on the FNIH's finances.This request for support under NIH's Other Transaction Authority (OTA) is, in fact, a do-or-die matter for theFNIH. While other funding sources have been explored and fundraising continues, none have or are likely to beforthcoming in a manner that is sufficiently timely to support the FNIH's efforts. Quite simply, without immediatefunding the FNIH will not be able to continue working on ACTIV and hence will be unable to support the NIH andits mission in this devastating COVID-19 health crisis.As requested in the Request for Negotiation to Establish a Public Private Partnership for COVID19 Researchsubmitted by the NIH, the FNIH provides herein information concerning the work the FNIH has and willundertake until July 31, 2020 and the costs to underwrite that work. While much of this activity concerns the DesignPhase, given the urgent need to make progress now, several critical implementation activities are anticipated tocommence before July 31, 2020.Please note that this request also includes a separate request for support of the Deloitte Consulting, LLC (Deloitte)contract with the FNIH. Deloitte was contacted to expand and support the FNIH capabilities given the speed andvolume of work required for ACTIV.",2020,2020,FOUNDATION FOR THE NIH,1796424,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Health workforce,2020 +C00842,1R01AI146081-01A1,Interplay between coronaviruses and nonsense-mediated mRNA decay pathway,"Coronaviruses (CoVs), which carry a large, single-stranded, positive-sense RNA genome, cause a variety ofdiseases in humans and domestic animals. Human CoVs (HCoVs) usually infect the respiratory tract andcause a range of symptoms varying from mild, such as the common cold, to more serious respiratory illnesseslike severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), caused by twohighly pathogenic HCoVs, SARS-CoV and MERS-CoV. SARS-CoV caused a worldwide epidemic in 2002-2003, resulting in more than 8,000 cases with an approximate mortality of 10%, while MERS-CoV emerged inSaudi Arabia in 2012 and has been disseminated into other countries in the Middle East, North Africa, Europe,and East Asia. HCoVs represent a major threat to public health and have the potential to cause a significantnegative economic impact. Currently, there are no approved vaccines and therapeutic agents against HCoVs.The development of effective control measures against CoVs requires a comprehensive understanding of viralgene expression strategies and host-CoV interactions. A plethora of studies have focused on investigating CoVbiology and have significantly contributed to our understanding of CoV replication mechanisms, including thestructure-function analyses of viral RNA elements as well as the viral proteins that are involved in viralreplication and assembly. However, there are still gaps in our knowledge of the post-transcriptional regulationof viral gene expression, as only a limited number of studies have addressed this area of CoV research.Particularly, very little is known about the cis-acting viral RNA elements and trans-acting host and viral factorsthat regulate CoV mRNA transcript stability. One newly emerging research area in virology is understandinginteractions between viruses and host mRNA surveillance pathways that prevent generation/accumulation ofunwanted gene products. We have demonstrated that CoV mRNAs are the targets of the nonsense-mediatedmRNA decay (NMD) pathway, one of the host mRNA surveillance pathways, and that viral N protein protectsCoV mRNAs from NMD. Our data suggest the importance of N-mediated NMD suppression for efficient virusreplication. The present application will study the interplay between the NMD pathway and CoVs by testing thefollowing hypotheses: UPF1, the principal orchestrator of NMD, binds to the 3' UTR of CoV mRNAs havingspecific motifs, undergoes phosphorylation, and recruits SMG6, an endonuclease, leading to endonucleolyticRNA cleavage; N binds to the 3' UTRs of NMD targets and prevents an NMD factor(s) from accessing thesetargets and/or N interacts with an NMD factor(s) and sequesters it away from the NMD pathway; and CoVmutants having an increased susceptibility to NMD, cannot replicate as efficiently as the parental viruses. Thedata obtained from these studies will provide mechanistic insights into NMD of CoV mRNAs and N-mediatedNMD pathway suppression, and will reveal the feasibility of novel strategies for attenuating CoVs throughincreased susceptibility to the NMD pathway.",2020,2024,The University of Texas Medical Branch at Galveston,309206,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2020 +C00844,1R21AI145372-01A1,Identifying Genetic Regulators and New Models of Wild Type Coronavirus Pathogenesis,"ABSTRACTSARS-CoV, and more recently MERS-CoV, are human coronaviruses that have emerged fromzoonotic populations to infect and cause severe disease in humans. Our understanding ofcoronavirus pathogenesis is largely limited to what can be observed in small animal models whichappear to recapitulate the disease seen in humans. The SARS-CoV mouse model relies on amouse adapted strain of virus, MA15, as the wild type human isolates replicate in mice but do notcause appreciable signs of disease. Replication models also fail to capture key aspects of thehuman response to infection - respiratory dysfunction, inflammation and other signs of disease.As such, replication models cannot be used to assess either antiviral therapeutics or vaccineefficacy. While mouse adapted SARS-CoV infection recapitulates many of the aspects of humanSARS-CoV disease, the virus has six point mutations scattered throughout the genome and wasnot generated until years after the end of the SARS epidemic. Passage models run the risk ofaltering virus tropism or replication from what occurs in the natural host and require sequencingand extensive analysis know the location and effect of each mutation. Importantly, coronaviruspassage experiments were recently restricted during the Gain of Function research pause andcould now fall under the HHS P3CO Framework, thus limiting our ability to rapidly identify diseasemodels for emerging pathogens. Additionally, a passage approach to generating a diseasemodels is time consuming, something that cannot be afforded in the context of a novel virusoutbreak. By generating a new mouse model of wild type SARS-CoV pathogenesis we willprovide an important tool for the evaluation of the pathogenic potential of emerging zoonoticcoronaviruses as well as a resource for testing novel therapeutics and vaccines. Additionally wewill identify genetic regulators that dictate a pathogenic response to wild type SARS-CoVinfection.",2020,2022,University of North Carolina at Chapel Hill,225750,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C00845,1R21AI153480-01,Broad Spectrum Anti-viral Compounds Targeting the SKI Complex,"The RNA Exosome and SKI complex are major cellular machines that degrade host RNA. Thismachine is required for several reasons in the cell including maintenance of current RNA levelsand to reduce the level of cytoplasmic RNA such that the RIGI and MDA5 sensors can detect viralRNA other than host RNA. The SKI complex was identified in a genetic screen as a host proteinthat interacts with both Influenza NS1 and MERS-CoV ORF4a. We were able to demonstrate thatknocking down these proteins in cells caused a reduction in viral replication and an increase inInterferon stimulated gene induction, irrespective of whether a virus was there or not. The SKIcomplex in yeast has been crystalized and upon modeling of the human structure, we in silicoidentified compounds that could potentially bind to a member of the complex, WDR61. In cellculture experiments, we identified 4 compounds from the 40 identified in the modeling, that blockInfluenza virus, MERS-CoV and SARS-CoV replication. In this proposal, we will determine themechanism of action of the compounds and NS1 and ORF4a on the SKI complex. We will alsoinitiate in vivo studies to evaluate the antiviral effectiveness of the SKI targeted plasmids onInfluenza virus and MERS-CoV mouse models. This work will validate a novel host target andcompounds directed at the SKI complex as broadly acting antivirals.",2020,2022,UNIVERSITY OF MARYLAND BALTIMORE,231750,Animals,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00846,1R56AI140872-01,Development of a safe and effective RBD-based vaccine against MERS-CoV,"In response to the NIH's call for countermeasures to prevent emerging infectious diseases, we willdevelop, test and manufacture the Middle East Respiratory Syndrome Coronavirus receptor binding protein(MERS-CoV RBD) vaccine as an innovative countermeasure. According to the WHO, MERS-CoV remains aserious global concern mainly due to its potential to cause explosive outbreaks with substantial socio-economicconsequences, if not controlled adequately. Therefore, an effective and safe vaccine is urgently needed. Wehave identified and produced at bench-scale a highly promising lead candidate vaccine antigen for MERS-CoVcomprised of the RBD of the spike (S) protein. This domain contains the major neutralizing epitopes and caninduce potent neutralizing antibody response and protection in animals against infection without causingantibody-dependent enhancement or eosinophilic pathology. Our MERS-CoV RBD is the leading vaccinecandidate because it elicits high titers of anti-RBD neutralizing antibodies, the major correlate of protectionagainst MERS CoV infection. It induces protection without eosinophilic immunopathology, the majordetrimental effect of vaccines that employ whole virus or full-length S protein constructs, and it is stable,enabling stockpiling for emergency use. To rapidly translate these laboratory findings, Texas Children'sHospital Center for Vaccine Development at Baylor College Medicine established a new Coronavirus VaccineDevelopment Product Development Partnership (CoV-PDP) comprised of New York Blood Center, UTMBGalveston, and PnuVax Ltd., as its industrial manufacturing partner. We have a proven track record ofinnovative and high impact scientific publications, the ability to develop and technology transfer recombinantprotein vaccines under cGMP, as well as experience with IND preparations and regulatory filings with the U.S.FDA. Through previous NIAID NIH funding the CoV-PDP has already developed and manufactured a SARS-CoV RBD vaccine. The specific aims of this application are: (1) Process development, pilot scale production,technology transfer and cGMP manufacture of the MERS-CoV RBD vaccine. Activities include scale-up ofexpression, assay development, formulation, and stability profiling, followed by technology transfer to PnuVax,where an engineering run and two cGMP production runs will be conducted. (2) Assessment of functionalityand antigenicity of MERS-CoV RBD vaccine, and demonstration of its immunogenicity in wild-type mice.Specifically, we will evaluate the vaccine for its functionality and antigenicity, followed by optimizing the antigendoses for optimal immunogenicity, including RBD-specific antibody and T-cell responses, as well as long-termimmune responses. (3) Evaluation of the immunogenicity, efficacy and safety of the vaccine in young and agedhDPP4-trensgenic mice well-known to be highly permissive to MERS-CoV infection and disease, followed bytesting in non-human primates. At the conclusion of these studies, cGMP-grade material will be available forGLP toxicology studies, IND preparation/submission, and first-in-humans clinical testing.",2020,2021,BAYLOR COLLEGE OF MEDICINE,433814,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2020 +C00847,1SC3GM132027-01A1,SARS-CoV Spike protein epitopes mapping with RNA Q-beta displayed peptides: A vaccine candidate.,"We propose to investigate a novel epitope mapping approach of SARS-CoV S proteins, using RNA phage Qβdisplayed peptides, and to evaluate the potential of these engineered hybrid phages as antibody neutralizingdeterminants critically important in the development of an efficacious vaccine candidate. Among the proteinscoded by the SARS-CoV genome, S protein mediates its cell entry and induces neutralizing antibodies. Thesepivotal functions are achieved by key amino acid peptide(s) through their exposed position on the virus surface.Phage Qβ is a small positive strand RNA virus with a 4.2 kb genome encoding 4 proteins. These are coat protein(Cp), maturation (or A2) protein, read-through or minor coat protein (or A1), and the RNA-dependent RNApolymerase or RNA replicase (RdRp) protein. As an RNA virus, phage Qβ possesses a key feature for its rapidevolution and adaptation: the RdRp protein that does not have proofreading activity during replication, resultingin higher mutation rates which simulate in vitro evolution and affinity-maturation processes. The A1 protein hasrecently been successfully used for fusion and display of randomized peptides in our laboratory, which isimportant because of its number and position on the phage surface. These fundamental concepts of RNA displaywill be exploited to investigate the following three specific aims:1. Design, construct, express and characterize hybrid phages Qβ exposing peptide of S protein epitopeson the exterior surface. Potential S protein continuous and discontinuous (chimeric) epitopes will be localizedand checked for exposition on A1 protein, using a combination of three computer bioinformatics software. Theidentified epitopes will be designed as oligonucleotides and cloned by fusion to the end of A1 minor coat proteingene for the novel RNA display system. These constructs will be characterized and expressed for hybrid phages(phagotopes) production. For any testing and selection of variant phages, we will use anti-S Abs.2. Randomize and optimize the major epitopes of S protein. A novel biopanning method will be developedfor selecting the appropriate randomized phages mimicking S protein epitopes (mimotopes) against the existingSARS-CoV and S protein mono/polyclonal antibodies. The selected mimotope(s) will be easily optimized andevolved through at least ten rounds of biopanning. The determinants of the randomized mimotopes pool willalso be classified by antibody type, and studied for any potential affinity to other viral cellular receptors differentfrom the natural SARS-CoV. Non-selected hybrid phages will be analyzed in correlation with the antibodies.3. Stabilize and initiate evaluation of the potential binding and neutralization of variant phages to SARS-CoV antibodies. We hypothesize that epitope peptide flanked by paired cysteines can be stabilized on thesurface of the mimotopes and/or phagotopes. The prepared hybrid phages will be analyzed and evaluated fortheir potential binding to all SARS-CoV antibodies and/or sera. The antibodies will be tested and classified foraffinity with the phagotopes and/or mimotopes in comparison to the wild type SARS-CoV or pseudotype model.",2020,2024,ALABAMA STATE UNIVERSITY,309206,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00848,1U01AI151810-01,"Emerging infections: surveillance, epidemiology and pathogenesis","To prepare for the next emerging infection, our goal is to establish a state-of-the-art EmergingInfectious Diseases Research Center with surveillance for the key disease syndromes - respiratory disease,encephalitis and fever of unknown origin- that have been observed most frequently associated with emergingviruses in the past few decades. In parallel, surveillance of animal and insect vectors will be performed toidentify the origins of and define transmissions patterns associated with, these novel emerging viruses. TheCenter includes four international surveillance sites-China, Hong Kong, Nepal and Ethiopia- which werecarefully selected on the basis of having either an established history of viral emergence or high potential tocapture such events. China, Hong Kong and Nepal are all situated in Southeast Asia, which has historicallybeen a nidus for many emerging viruses such as H5N1 influenza, SARS Coronavirus, Severe Fever andThrombocytopenia virus, and the very recently reported Alongshan virus. Ethiopia, along with NortheasternAfrica, is at high risk for emergence of MERS Coronavirus (MERS-CoV) due to endemicity of MERS in camels,a key reservoir in the region. To identify novel or emerging viruses, we will use complementary virus family-specific consensus PCR and unbiased next generation sequencing approaches and then sequence theircomplete genomes. Subsequently, we will generate key reagents essential for establishment of diagnosticassays and the study of fundamental aspects of viral pathogenesis, epidemiology, and immune control. Theseinclude development of cell culture systems, targeted RT-PCR/PCR assays, serological assays, monoclonalantibodies for antigen detection and potential therapeutic applications, mouse models of infection, and ifappropriate, ferret models of virus transmission. An additional component of the center is international capacitybuilding. Initial efforts focus on two exemplar viruses: MERS-CoV, a recently emerged virus, and a highlyvariant Dengue virus, Dengue virus 5, which is has prevalence and emergence potential. MERS-CoV is adeadly zoonotic respiratory pathogen with a case fatality rate of ~35% to date. We will implement surveillancefor these viruses and develop additional reagents and assays to characterize their epidemiology andpathogenic potential. These efforts will establish and validate the critical infrastructure necessary to respond toa new emerging infectious disease. In the event of a new outbreak, efforts will be reprioritized to focus onresponse to the new emerging threat. The priorities, in order, are: (1) Human and animal surveillance fornovel/emerging viruses; (2) Assay and reagent development; (3) Define epidemiology of novel/emergingviruses; (4) Pathogenesis, immune control, transmission and treatment of novel/emerging viruses.",2020,2025,WASHINGTON UNIVERSITY,1683114,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease models | Animal source and routes of transmission | Disease transmission dynamics,2020 +C00851,3DP1DA041722-06S1,Development of a Targeted Nitric Oxide-Related Drug to treat SARS-CoV-2,"COVID-19-Related Administrative Supplement to DP1 DA041722 under PA-18-591 and NOT-DA-20-047PROJECT SUMMARYThe worldwide pandemic of the 2019 novel coronavirus, or COVID-19, has led the research community tobelieve the possibility that it could affect some populations with substance use disorders or HIV particularlyhard. Therefore, we propose new work here that is ""in scope"" with our parent NIDA DP1 grant (DP1DA041722) that would potentially address the pandemic, at least in part, by developing an anti-viral drug tofight the infection. We propose, as listed in NOT-DA-20-047, to perform ""research to develop therapeuticapproaches for comorbid SARS-CoV-2 infection."" In the parent DP1 grant, we are studying the nitric oxide(NO)-related posttranslational modification of proteins, which we previously named S-nitrosylation, in patientswith HIV-associated neurocognitive disorder (HAND) and drug use, particularly methamphetamine. During thecourse of these studies, we developed a novel series of therapeutic agents in the class of compounds calledaminoadamantane nitrates, with the lead drug designated NitroSynapsin, that have shown activity in protectingneurons in the context of HIV/methamphetamine abuse as well as in the context of Alzheimer's disease andother neurologic disorder. Our novel approach concerns the fact that this family of agents that we developedmay also show activity at the ion channel in the envelope of the SARS-CoV-2 virus, the causative agent of theCOVID-19 pandemic. The mechanism of action (MOA) that we propose against SARS-CoV-2 is bestsummarized as follows:Compounds in the aminoadamantane family are generally known to block ion channels in envelope viruses,including SARS-CoV-2, which causes COVID-19 respiratory disease. Moreover, nitric oxide (NO) and relatedcompounds have been reported to inhibit this class of viruses. We reasoned in a novel fashion that thetargeted delivery of NO-related species to the virus would avoid systemic side effects of NO-like drugs. For thispurpose (but originally for use in the brain), we had devised a series of aminoadamantane nitrates, with theaminoadamantane moiety acting as a ""guided missile"" to enter the viral envelope channel and then deliver a""warhead"" of a nitro group directly to the virus to disrupt viral activity. Accordingly, we propose to rapidly testour drugs in an ongoing screen against SARS-CoV-2 viral activity in our Calibr Drug Development Core Facilityat The Scripps Research Institute in La Jolla, California.",2020,2021,SCRIPPS RESEARCH INSTITUTE,177500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2016 +C00852,3K01DA043412-04S1,Preventing HIV infection among people who inject drugs during COVID-19,"This application is being submitted in response to NOT-DA-20-047. Injection drug use has contributed to newHIV outbreaks in many regions of the United States. The parent K01 award seeks to improve the delivery ofantiretroviral pre-exposure prophylaxis (PrEP) to people who inject drugs (PWID) through syringe serviceprograms (SSPs), which provide essential HIV prevention services to this population. Large-scale public healthemergencies, as well as the measures undertaken to mitigate them, can increase HIV risk among PWID (e.g.,by impacting drug market characteristics and drug-related and sexual risk behaviors) while also impacting thedelivery of essential prevention services. This administrative supplement proposes longitudinal, mixed methodsdata collection to understand the impacts of the 2019 Novel Coronavirus (2019-nCoV or COVID-19) on HIV-related risk among PWID and SSPs' capabilities to provide PrEP and other HIV prevention services over thecourse of the pandemic. Due to restrictions on in-person research encounters in the context of infectiousdisease transmission, over the course of six months, we propose virtual (video-conference) qualitativeinterviews with 40 PWID and 20 SSP staff as well as modified, weekly quantitative ecological momentaryassessment (EMA) with participating SSPs to understand evolutions in PWID risk behaviors (Aim 1), SSPorganizational functioning and staff wellbeing (Aim 2), and EMA feasibility and SSP service provision in thecontext of a large-scale emergency (Aim 3). Guided by the socio-ecological model, our mixed methodsanalyses will provide critical evidence on how to sustain the delivery of PrEP and other essential HIVprevention services to at-risk PWID during large-scale public health emergencies. Our primary innovations arethe longitudinal examination of individual and organizational responses to the COVID-19 pandemic over time,the use of virtual data collection methods (including EMA with SSPs) that leverage the parent K01 award'snetwork of community research collaborations, and the mixed methods approach to eliciting multiplestakeholder perspectives on the impacts of this unprecedented pandemic on HIV prevention with a vulnerablesubstance-using population. Findings from this supplement will inform efforts to promote sustained HIVprevention service delivery during future public health emergencies while also enhancing the success of theparent K01 award focused on SSP-based implementation of PrEP for HIV prevention in a highly sociallymarginalized population.",2020,2022,BOSTON UNIVERSITY MEDICAL CAMPUS,107979,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions,2017 +C00853,3K23AI143967-01S1,Predictors of Influenza-Associated Absenteeism and Impact of Vaccination in a Cohort of Guatemalan Agricultural Workers,"This is an Administrative Supplement Application to carry out SARS-CoV-2 PCR testing in an existing NIAID-funded study (1K23AI143967) evaluating the clinical and economic impacts of influenza in Guatemalanagricultural workers. The Parent Study includes the enrollment of an existing cohort (n=2,706) of Guatemalanagricultural workers with high rates of chronic medical conditions (CMCs) into a prospective active surveillancesystem for cough and fever (severe acute respiratory illness [SARI]). Workers meeting the case definition aretested for influenza A/B and RSV (Roche cobas® Liat RT-PCR Assay) and then clinical and economicoutcomes are assessed using follow up surveys and company reported absenteeism and productivity data. This Administrative Supplement will allow us to maintain our cough/fever surveillance system, given anincrease in expected cases due to SARS-CoV-2, and to perform RT-PCR testing for SARS-CoV-2. Wehypothesize that, similar to influenza, COVID-19 will place a significant clinical and economic burden onagricultural workers, especially the large proportion with CMCs, such as chronic kidney disease of unknownorigin (CKDu, aka ""Mesoamerican nephropathy""), given existing data showing a significantly increased risk ofsevere disease. Evaluating these outcomes in an existing prospective cohort will allow us to measure theseburdens on a population-level, which will provide critical data in understanding the true impact of disease. Weaim to implement our SARS-CoV-2 testing immediately, analyze and disseminate our results quickly, andmake samples from our specimen biobank (annual blood and urine, acute illness respiratory and blood)available for additional research.",2020,2022,UNIVERSITY OF COLORADO DENVER,49756,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Farmers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Disease pathogenesis,2020 +C00854,3P01AI039671-22S1,Dysregulated Co-inhibitory Pathways Associated with Severe COVID-19 Immunopathology,"COVID-19, caused by novel coronavirus SARS-CoV-2, has recently affected over 600,000 people and has caused more than 30,000 deaths worldwide. Dysregulated immune responses against SARS-CoV-2 virus are a critical component of COVID-19 that can lead to severe respiratory failure (SRF). The dysregulated type 1 interferon (IFN-I) production by innate immune cells are likely involved in immunopathogenesis. However, the molecular mechanisms by which the virus causes lethality are not known. It has been found that COVID-19 patients with SRF exhibit a cytokine storm with hyper activated T cells characterized by pro-inflammatory cytokine production of GM-CSF, IFN-γ, and TNF-α, though paradoxically, the T cells express high level of co-inhibitory receptors that are thought to limit this aberrant response. These data indicate there are inadequate inhibitory signals on T cells in severe disease. We have identified TIGIT as a critical co-inhibitory receptor expressed on T cells that plays a central role in orchestrating T cell activation and immune homeostasis in autoimmunity, cancer and viral infection, and its expression was found to be coordinated with the PD-1/TIM-3 module in mice. However, our lab recently discovered that while IFN-I drives expression of this module it surprisingly decreases TIGIT expression in humans implicating a unique function of TIGIT during IFN-I responses on human T cells. Moreover, we developed a gene regulatory network using high resolution transcriptional profiling that allows identification of regulatory factors for co-inhibitory receptor expression during IFN-I response. This leads to our overall hypothesis that delayed IFN-I response to SARS-CoV-2 in older individuals disrupts the T cell co-inhibitory response, leading to T cell hyperactivation and severe illness. Specifically, attenuated TIGIT expression on T cells allows aberrant cytokine release which fuels the cytokine storm in severe COVID-19. Moreover, pre-clinical data demonstrated that TIGIT signaling limits immunopathology without affecting viral load in vivo. Thus, our goals are to: 1) identify the molecular mechanism for the dysregulated immune program leading to hyper T cell responses in COVID-19 patients and to identify potential targets. We will probe dynamic T cell responses by incorporating comprehensive multi- omics single cell analysis in patients with mild and severe manifestation of COVID-19 compared to healthy individuals; 2) we will explore the mechanism for driving hyperactivation of T cells in severe COVID-19. Our previously established gene regulatory network for IFN-I response on T cells will be integrated with data acquired from our single cell analysis. This will allow us to identify the key regulatory factors controlling TIGIT expression under IFN-I response and may allow the identification of novel therapeutic targets; 3) Finally, we will determine the therapeutic potential of TIGIT mediated co-inhibitory signaling in COVID-19 by investigating whether agonistic TIGIT antibodies can ameliorate the hyperactivated state of T cells in severe COVID-19 patients. Studying how co-inhibitory signals modulate T cell responses to SARS-CoV-2 may reveal novel molecular targets for COVID-19 immunotherapy.",2020,2021,YALE UNIVERSITY,260931,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C00855,3P01AI089473-06S1,Human Epidemiology and Response to SARS-CoV-2 (HEROS),"This request is in response to NOT-AI-20-031 for supplement funding in response to the CoVID-19 emergency. COVID-19, the infectious disease caused by SARS-CoV-2, is rapidly affectinghumans around the globe. While initial epidemiological data have focused on cases thatresulted in severe respiratory disease seen predominantly in adults, little information regardingthe infection burden in children is available. This is complicated by the observation that manyvirologically-confirmed cases in children are asymptomatic. Undocumented, and likelyinfectious, cases could result in exposure to a far greater proportion of the community thanwould otherwise occur. Indeed, it has been proposed that undocumented (or silent) infectionsare the source for almost 80% of documented infections; thus, it is critical to determine the silentand symptomatic infection rate in children. To overcome challenges for clinical studyimplementation imposed by current healthcare access restrictions, a surveillance study underdesign will enroll and prospectively observe eligible children, and their family members, that arecurrent participants in our NIH-funded, ongoing, birth cohort studies. These children and theirfamilies are known to research staff and as part of their participation in HFHS studies, they havealready been exposed to the procedures involved in a surveillance study. We are requestingsupport for the pediatric studies aligned with our Microbiota and Allergic Asthma PrecisionPrevention (MAAP2) (PI: Johnson, Ownby P01AI089473) to participate in the multi-centersurvey entitled Human Epidemiology and Response to SARS-CoV-2 (HEROS), Protocol #DAIT-COVID-19-001. Our primary objective is to report the incidence of SARS-CoV-2 infection(detection of virus in nasal secretions) over time in cohort children (index child) and householdcontacts (caregivers and siblings). A secondary objective is to compare SARS-CoV-2 infectionstatus and antibody development for index children/siblings with atopic conditions (e.g. asthma,eczema) versus children without atopic conditions. As an exploratory aim, we will investigatewhether SARS-CoV-2 infection (as determined by virus detected in nasal secretions) isassociated with the presence of virus in stool. Our targeted enrollment is 300 families recruitedover a 2-week period and followed for a minimum of 6 months. At predetermined intervals,biological samples (nasal swabs, peripheral blood, stool) will be collected by the caregiver athome using materials provided to the family. Symptom and exposure surveys will be completedremotely via a smart phone, on-line, or telephone at the time of biological sample collection.This timely, multi-site study can be rapidly implemented and realistically conducted withoutnecessitating any visits to a clinical research center and will provide invaluable information onthe infection burden of SARS-CoV-2 in children.",2020,2021,HENRY FORD HEALTH SYSTEM,134318,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C00856,3P01AI091580-09S1,Understanding T cell responses and T cell signaling in human airway organoids with SARS-CoV-2 infection,"The SARS coronavirus-2 (SARS-CoV-2) has rapidly emerged over the past four months leading to a criticalpandemic of coronavirus disease (COVID-19) with over 1.4M cases worldwide(https://coronavirus.jhu.edu/map.html) and roughly 100,000 projected fatalities in the US alone by August2020 (See https://covid19.healthdata.org/projections). SARS-CoV-2 causes a lethal ARDS. Despite ourimproved mechanistic understanding of ARDS, intervention clinically is challenging. NOT-AI-20-31 indicatedseveral needs, such as development of reagents and assays for virus characterization, understand criticalaspects of viral infection, replication, pathogenesis, and transmission, identification and evaluation of thecellular and humoral immune responses to SARS-CoV-2, which we address in this proposal. Indeed, there is an urgent need to understand the immunopathology of COVID-19 and study theinteractions of the lung epithelium and tissue, the immune system and the virus to understand the biology ofthis multipartite interaction. We need to better understand the immunopathology of COVID-19 to explorenovel therapeutic approaches that have the potential to work in COVID-19 patients. Our proposal addresses this need from the perspective of the lung epithelium response to SARS-CoV-2 infection and from a T cell perspective in COVID-19. Simultaneously, or efforts will also provide asharable research platform of lung airway organoids/SARS-CoV-2/immune cells that will expedite testing ofexperimental therapeutics. Results from my supplement program will be shared with Drs. Gordon, Looney,and Krummel in our 'RapidPath' program (see supporting letter) to promote rapid discovery and progressand will be compared to insights from COVID-19 patient immune systems, being simultaneously profiled inthe UCSF IMPACC project. In this this Administrative Supplement we will capitalize on my lab's establishedexpertise in T cell signaling, T cell activation, antigen recognition, inflammation, and autoimmune diseases.Those are broad topics of the parent P01 (2P01AI091580, Weiss). Uniquely, we will combine our T cellexpertise with our expertise in the generation and studies of epithelial cell organoids. We already have an""Airway Organoid Biobank"" that we will expand as a resource for the community. We will characterize theepithelial response to six different SARS-CoV-2 strains compared to H1N1pdm virus, using airwayorganoid-, single cell RNAseq-, and CyTOF- technology (Aim 1). In order to better understand SARS-CoV-2and adaptive immunity, we will obtain mechanistic insights into T cell activation and T cell signaling in thecontext of SARS-CoV-2- and H1N1pdm- infection of seven, diverse Airway Organoids and two NSCLCorganoids (Aim 2). High-resolution imaging and CyTOF analysis of these ""virus-T cell-organoids"" willprovide much needed immunological insights into SARS-CoV-2 and its T cell biology as indicated in NOT-AI-20-31 and will synergize with other projects in 'RapidPath' and in UCSF IMPACC programs.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,107532,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C00857,3P01AI138938-02S1,Human monoclonal antibodies for prophylaxis and therapy against the new coronavirus,"The WHO and US authorities have declared a public health emergency over the recent outbreak of a newcoronavirus (CoV) originating from Wuhan, China (nCoV-2019, recently renamed SARS-CoV-2 andresponsible for causing the coronavirus disease termed COVID-2019). The discovery of human monoclonalantibodies to this new CoV and obtaining a molecular understanding of its target epitopes will advance thedevelopment of diagnostics, therapeutics and vaccines to limit virus spread. The overall goal of this proposal is to discover and characterize potent broadly neutralizing antibodiesto nCoV-2019 that also neutralize closely related strains of CoV such as SARS and other variants currentlyfound in bats but likely to be able to produce human infections in the future. The Nussenzweig laboratoryhas developed robust methods to isolate, recombinantly produce and characterize human antibodies fromthe memory B cells of individuals infected by a series of different pathogens including HIV-1, Flavivirusesincluding Zika, and Hepatitis B virus (1, 2). These methods have also been used by other laboratories toisolate neutralizing antibodies to malaria, Ebola, influenza and other human infections (reviewed in (3)). TheBjorkman laboratory has performed structural studies using these antibodies to obtain information that directsvaccine design and therapies (2, 4-23). In Aim 1, we obtain samples from nCoV-2019 convalescing individuals (see letter from Dr. WesleyVan Voorhis). Serum samples will be tested for binding to the trimeric nCoV-2019 spike protein (S) and to theisolated receptor binding domain (RBD) of the S protein (see letter of collaboration from Dr. John Pak at Chan-Zuckerberg Biohub). Individuals with high titers against S and RBD will be recruited for large blood donations.Antibodies will be identified from the memory B cells of these individuals. In Aim 2 we will clone and expressthe antibodies obtained in Aim 1. The anti-nCoV-2019 antibodies will be tested for binding to the S proteinfrom Severe Acute Respiratory Syndrome (SARS) and other closely related bat-derived CoV to test for cross-reactivity. Any promising antibodies will be evaluated for neutralizing activity (see letter by Dr. TimothySheahan at the University of North Carolina). In Aim 3 Dr. Bjorkman will solve crystal structures of antibodyFabs, and cryo-EM structures of coronavirus spike trimers complexed with Fabs from antibodies identifiedfrom Aims 1 and 2. In addition to helping guide vaccine development through the identification of neutralizing targets, theproposed discovery of human monoclonal antibodies to nCoV-2019 and related viruses bears a significanttranslational potential, such as the treatment and prophylaxis of severe medical conditions associated withnCoV-2019 infection by passive antibody transfer.",2020,2022,ROCKEFELLER UNIVERSITY,400050,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +C00858,3P30AG019610-20S1,Arizona Alzheimer's Disease Core Center,"The coronavirus SARS-CoV-2 (Covid-19 or 2019-nCoV) emerged in Wuhan, China, in late 2019 and thenrapidly spread worldwide. It causes severe acute respiratory syndrome (SARS) with substantial morbidity andmortality. Little is yet known whether the CNS is involved, but other coronaviruses are known to invade thebrain. There is as yet, however, no published data on the presence or neuropathological consequences ofCNS SARS-CoV-2 in infected humans. This project aims to fill this important knowledge gap.The Arizona ADCC became the NIA's first statewide AD Center in 2001. Since then, it has establishedClinical and Neuropathology Cores that are world-class resources of longitudinally assessed individuals, and,together with an extraordinary ancillary Brain and Body Donation Program, annually contribute on average 80autopsied subjects. In this supplemental application we propose to conduct important studies probing theextent and consequences of SARS-CoV-2 CNS infection in an estimated 100 or more subjects coming toautopsy over an 18 month period spanning the global pandemic. The project is supported by an extremelystrong, multidisciplinary team. Specific Aim 1 will determine the prevalence of CNS infection with SARS-CoV-2in consecutive autopsies, using postmortem nasal swab, postmortem blood serology and assay of multiplebrain regions for SARS-CoV-2 RNA. Specific Aim 2 will assess the gene expression effects of brain regionalSARS-CoV-2 infection using RNAseq transcriptomics. Deconvolution analysis will infer gene expressionchanges separately for neurons, microglia, astrocytes, oligodendrocytes and endothelial cells. Hypotheticalgene expression effects would include those typical for inflammatory responses, cell death and demyelination.Additionally, this analysis will put SARS-CoV-2 findings into perspective vs other microbial or viral presence asdetected by their specific transcripts, reflecting past pathogen exposure history. Specific Aim 3 will determinethe neuropathological correlates of the findings from Specific Aims 1 and 2, by surveying the brain for typicalviral-associated histopathology including meningitis, encephalitis, microglial nodules, perivascular mononuclearcell cuffing and demyelination, and by determining with immunohistochemistry and in-situ hybridization whetherspecific cell types are infected. These findings may yield critical clues useful for devising diagnostic andtherapeutic strategies for possible neurological manifestations of SARS-CoV-2 and the planned studies providean unprecedented opportunity to survey the prevalence and extent of brain invasion by a novel pathogenduring a worldwide pandemic.",2020,2021,ARIZONA STATE UNIVERSITY-TEMPE CAMPUS,407889,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2001 +C00859,3R00AI123498-03S1,Structural Studies of the Corona Virus Life Cycle,Coronaviruses are a diverse family of viruses infecting many animals including humans. The 21stcentury is now experiencing its third outbreak of a novel pathogenic coronavirus that has crossed from ananimal host into humans for the first time. The outbreak of SARS-CoV-2 is unprecedented among humancoronaviruses in its size and the speed of its spread. Countering this viral outbreak will require a detailedmechanistic understanding of virus protein function. The goals of this project are to gain highly detailedinformation about the SARS-CoV-2 replication complex using single-particle cryo-electron microscopy. We willuse this high-resolution imaging technique to determine structures of the SARS-CoV-2 polymerase complexbound to substrates and small molecule antiviral drugs. We will complement these structural analyses with adetailed biochemical study of protein-protein and protein-RNA interactions and the influence of theseinteractions on SARS-CoV-2 polymerase activity. These studies include mutagenesis of key interfaces in theprotein complex and testing of the recombinant proteins in polymerase activity assays. These studies have thepotential to illuminate the mechanisms used by the SARS-CoV-2 polymerase complex to replicate its viralgenome and provide a mechanistic understanding of antiviral therapeutic action key to the development ofnovel antiviral therapeutics to treat COVID-19.,2020,2020,UNIVERSITY OF WISCONSIN-MADISON,107532,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2020 +C00860,3R01AG058639-02S1,BRAIN-2 Administrative Supplement with ORCHID-BUD,"Medical teams globally are consumed in caring for patients with respiratory failure and acute comorbiditiescaused by Coronavirus Disease 2019 (COVID-19). To understand the full impact of this pandemic on the livesof survivors and the magnitude of this emerging public health crisis, we must study the brain. We helped definethe plague of disabling features suffered by millions of intensive care unit (ICU) survivors called Post-IntensiveCare Syndrome (PICS), characterized by an acquired Alzheimer's disease and related dementia (ADRD), post-traumatic stress disorder (PTSD), and depression. Approximately 10% to 15% of COVID-19 patients develophypoxemia requiring hospitalization, which can lead to acute respiratory distress syndrome and the need forlife support, including mechanical ventilation. Up to 26% of hospitalized patients with COVID-19 require ICUadmission. We hypothesize that COVID-19 survivors who are hospitalized will have a high burden of PICS-related acquired-ADRD, PTSD, and depression. To test this hypothesis, we propose this NIH AdministrativeSupplement to the BRAIN-ICU-2 Study (R01AG058639). This Administrative Supplement will allow us to usethe BRAIN-ICU-2 long-term follow-up infrastructure to collect 6-month cognition, PTSD, and depression datafor a NHLBI-sponsored randomized trial (ORCHID) that is evaluating hydroxychloroquine versus placebo on15-day death, mechanical ventilation, or oxygen supplementation. We will ascertain these 6-month outcomesusing a comprehensive phone battery that incorporates robust neuropsychological tests for memory, attention,language, reasoning, and executive function, and diagnostic evaluations for PTSD and depression. OurAdministrative Supplement is titled ""Outcomes Related to COVID-19 treated with Hydroxychloroquine amongIn-patients with symptomatic Disease - Brain Outcomes and Psychological Distress (ORCHID-BUD)"" and willconduct 6-month follow-up assessments in 270 adults who are hospitalized with COVID-19 infection andsurvive. ORCHID-BUD has the following specific aims: (1) To determine the epidemiology (i.e., prevalence) ofcognitive impairment (i.e., acquired-dementia) at 6 months and if hydroxychloroquine administration isassociated with improvement in these same outcomes; (2) To determine the epidemiology of PTSD anddepression at 6-months, and if hydroxychloroquine administration is associated with improvement in thesesame outcomes, and (3) To identify modifiable risk factors (e.g., sedatives, isolation, intravenous fluids,pressor, ACE-inhibitor or ARB use, etc.) associated with worse long-term cognitive impairment, PTSD, anddepression at 6 months. To our knowledge, this investigation will be the first ever to conduct robustneuropsychological assessments for SARS, MERS or COVID-19 survivors, and the first among COVID-19 toconduct diagnostic PTSD and depression assessments. This Administrative Supplement will leverage BRAIN-ICU-2 and ORCHID's resources to conduct a high impact and novel investigation at relatively low cost and helpprovide a comprehensive evaluation of COVID-19's effect on long-term cognitive and psychological outcomes.",2020,2024,Vanderbilt University Medical Center,424619,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences",2019 +C00861,3R01AG063543-02S1,Using the senolytic fisetin to suppress mortality in aged mice acutely exposed to murine beta-coronavirus,"Aging and the chronic diseases associated with aging place a tremendous burden on our healthcare system andreduce quality of life for the elderly. As our world population ages dramatically over the next three decades, theburden will only increase. Hence, there is a great need to discover fundamental mechanisms of aging to developrationale strategies for minimizing the impact of aging on our health and economy. This fostered the Gerosciencehypothesis, which posits that therapeutically targeting fundamental mechanisms of aging will yield a largerdividend in terms of improving the health of an aging population than would treating individual age-relateddiseases. The fundamental mechanism of aging where this has borne out most successfully to date is throughelimination of senescent cells. Senolytic drugs were first described by us and others in 2015 and have alreadyfostered multiple clinical trials beginning in 2018. In mice, senolytics improve physical function, tissue health andsuppress all cause mortality. COVID-19 has emerged as an urgent threat to our aged population. The goal of the parent project is to fully define the mechanism by which an aged / senescent immune systemdrives morbidity and mortality using mice as a model organism. The goal of this revision is to use the knowledgeand resources we have to study the role of cellular senescence in driving adverse outcomes in aged organismsacutely exposed to novel viral pathogens. Preliminary data indicate that mice with a substantial senescent cellburden respond much worse to inflammatory challenges than mice without senescent cells. Furthermore,exposure to normal pathogens carried by wild or pet store mice is sufficient to kill old experimental mice housedin specified pathogen-free conditions, but it does not kill young mice. Here, we propose to use this experimentalparadigm to determine if senolytics, drugs that specifically kill senescent cells, suppress mortality in aged, obese,diabetic or diseased mice. The immediate goal of this revision is to generate sufficient preclinical data to supportclinical trials using nutraceuticals with senolytic activity to prevent adverse outcomes in those at high risk ofCOVID-19 infection or grave illness after infection. The long term goal of this project is to enable rigorouslytesting the Geroscience hypothesis.",2020,2024,UNIVERSITY OF MINNESOTA,424619,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Prophylactic use of treatments,2019 +C00862,3R01AI052116-18S1,COVID19 Admin Supplement to Rapidly Translate Immunobiology for Patient Benefit,"This is an administrative supplement to the parent R01 AI052116 ""SPATIOTEMPORAL CONTROL OF T CELLSYNAPSE STABILIZATION AND SIGNALING"" which for my entire career has been my central grant forstudies of T cell interactions leading to tolerance or activation. Here, we apply our considerable immune andtissue-immune experience towards generating and exploiting a RapidPath platform to find rapid actionableimmunotherapeutic targets for COVID-19 patients for limiting damage due to SARS-CoV-2 infections.In aim 1 of this study, we will build a lung plus virus plus immune platform in which the role of specific T cells ofdifferent activation status -alone and through their modulation of myeloids cells-will be assessed in theresponse of damage to lung epithelium plus/minus endothelium (organoid, with Roose/Gordon and lung slicewith Looney). This supplement will interact intensely with parallel studies of those labs and also with ongoingstudies that will also leverage RapidPath but are not in this first cohort of applications. This will provide `best inclass' model systems in human biology and will leverage our collective expertise. In aim 2 of this study, wewill test a panel of immunomodulatory drugs to determine if acute exposure to them can modulate lungdamage, likely through modulating myeloid biology. The net result will be validated immunotherapeuticpaths in robust pre-clinical human systems that recapitulate key features of COVID-19.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,312232,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Prophylactic use of treatments | Adverse events associated with therapeutic administration,2020 +C00863,3R01AI095366-07S1,Rapid Generation of Vaccine Candidates Against Novel Wuhan Coronavirus (SARS-CoV-2) Using the Bacteriophage T4 Nanoparticle Platform,"This proposal aims to rapidly generate vaccine candidates against the 2019 novel coronavirus SARS-CoV-2. Since its emergence about three months ago, this virus has caused more than 120,000 infections and 4,300deaths worldwide and is rapidly spreading to virtually every country including the United States. This globalhealth emergency must be immediately addressed by rapidly developing medial countermeasures. Our bacteriophage (phage) T4 vaccine platform is uniquely suited to address this threat. Developed in PI'slaboratory, the T4 vaccines have been proven to generate robust humoral as well as cellular immune responsesand confer complete protection against anthrax and plague in multiple animal models including mice, rats,rabbits, and macaques. The T4 vaccines do not need an adjuvant as its surface structure mimics the Pathogen-Associated Molecular Patterns (PAMPs) of viral pathogens and stimulate strong innate and adaptive immunity. The 120 x 86 nm phage T4 capsid is packaged with 171 kb genome and decorated with two non-essentialouter capsid proteins; 870 molecules of Soc (small outer capsid protein) and 155 copies of Hoc (highly antigenicouter capsid protein). In specific aim 1, a series of T4-corona phages will be constructed by incorporating SARS-CoV-2 virion components individually and in combinations, by CRISPR engineering. The gene encoding theentire spike ectodomain will be inserted into phage genome under the control of the strong CAG promoter. Uponimmunization, host cells (myocytes and antigen presenting cells at the site of immunization) take up phageparticles and secrete the ectodomain trimers continuously, stimulating the immune system for weeks to months.The gene for the receptor binding domain (RBD) of S protein will be inserted such that the RBD will be expressedin host cells, as well as in E. coli as a Soc fusion protein which will then be displayed on phage capsid up to 870copies per capsid. The ectodomain of E protein will be fused to Hoc and displayed up to 155 copies per capsid.Finally, ~400 copies of N protein will be packaged inside the capsid as part of the scaffolding core. In specific aim 2, the above T4-corona recombinant phages will be evaluated for elicitation of SARS-CoV-2 virion-specific immune responses in a mouse model. Mice will be immunized with purified phage particlesintramuscularly and the immune responses will be quantified by ELISA, competitive receptor binding, ELISpot,and virus neutralization assays. We expect that the T4-corona vaccines will elicit robust antibody and cellularresponses and also inform which candidate(s) will be most effective in blocking SARS-CoV-2 infection. We have streamlined the CRISPR engineering such that the proposed T4 vaccines can be constructed inabout 4 weeks and the animal testing can be completed in about 12 weeks. The candidate vaccines will then beavailable for clinical trials and vaccine manufacture. The T4 vaccine will be exceedingly easy to manufacture,scale, and distribute globally, and could potentially lead to a breakthrough to avert the coronavirus crisis.",2020,2024,PURDUE UNIVERSITY,381463,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Vaccine design and administration,2020 +C00864,3R01AI124465-05S1,Mechanism of BET Proteins in Th17 Cell Differentiation,"This administrative supplement application is submitted for the parent award (5R01AI124465) inresponse to NIAID's Notice of Special Interest (NOT-AI-20-031) ""Severe Acute Respiratory SyndromeCoronavirus (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19)"", as well as ""AdministrativeSupplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp - Clinical TrialOptional)"" (PA-18-591). The outbreak of the new coronavirus (SARS-CoV-2) infection is spreading toevery continent around the world at an astonishing speed. As of April 15, 2020, coronavirus disease2019 (COVID-19) has been confirmed in 2,035,764 people worldwide, causing a mortality of 6.42%,exceeding far beyond a mortality rate of <1% from influenza. Effective treatment is urgently needed tostop the rapid spread of SARS-CoV-2 infection in this devastating pandemic. While current focus is ondeveloping novel therapeutics including antivirals and vaccines, mounting evidence show that manysevere COVID-19 patients suffer from respiratory failure by acute respiratory distress syndrome(ARDS), the leading cause of COVID-19 mortality. In this study, we aim to address this majorunmet medical need. Clinically, host cells elicit two-phased responses to SARS-CoV-2 infection. Inan early incubation and non-severe stage, immune cells such as macrophages detect the virus andproduce cytokines to eliminate the virus. But, when a protective immune response is impaired, thevirus propagates, and the disease is transitioned to a severe stage where innate inflammation isinduced by virus-caused massive tissue damage with uncontrolled cytokine release (aka CytokineStorm) from inflammatory macrophages and granulocytes, resulting in ARDS in the lungs. Ascendedpro-inflammatory cytokines such as IL-6, IL-10, IL-17, GM-CSF, MCP-1, IFN-γ, and TNF-α arereported in severe COVID-19 patients. Lung hyper-inflammation is the main cause of life-threateningrespiratory disorders at the severe stage. Notably, our study shows that transcriptional activation ofthese inflammatory cytokines is directed by major transcription factors NF-kB and STAT3 in concertwith chromatin regulators BRD2 and BRD4, and that their activities can be effectively blocked bychemical inhibitors. Motivated by our findings, in this study, we propose to identify and repurposeFDA-approved drugs to suppress SARS-CoV-2-induced cytokine storm through simultaneouslyblocking NF-kB and STAT3 signaling pathways. We will achieve this goal by addressing the twospecific aims: (1) identify FDA-approved drugs to block uncontrolled cytokine release induced bySARS2-CoV-2; (2) validate chemical inhibition of hyperinflammation in human immune cell linesincluding human peripheral blood mononuclear cells from COVID-19 patients.",2020,2021,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,342914,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00865,3R01AI125215-04S1,Targeting TLR Signaling Pathways to Blunt Pathogen-mediated Acute Lung Injury,"For decades, a ""one bug, one drug"" approach has characterized development of vaccines or treatments forspecific infectious diseases. We propose a different approach based on the development of novel treatment ofinfectious diseases by capitalizing on common host innate immune responses that are triggered during infection by influenza and other priority pathogens. Influenza virus infects up to 5 million people yearly worldwide,killing as many as ~500,000. Our strong experimental evidence demonstrates that the potent TLR4 antagonist,Eritoran (Eisai, Inc.), as well as multiple other TLR4 antagonists, significantly decreased both acute lung injury(ALI) and mortality when administered therapeutically to influenza-infected mice. Eritoran not only blocks influenza-mediated release of host-derived ""danger-associated molecular patterns"" (DAMPs), but also bluntedDAMP-mediated TLR4 signaling in macrophages that normally results in a ""cytokine storm."" While we haveelucidated several novel mechanisms by which influenza mediates ALI and lethality that are counteracted byEritoran therapy (e.g., release of host-derived DAMPS that signal through TLR4; increased tight-junction permeability leading to pulmonary edema; a role for IL-1α/β in lethality), our understanding of the overall innateimmune signaling pathways that control influenza-induced ALI and Eritoran-mediated protection remains incomplete, necessitating further investigation to develop a highly efficacious host-directed therapy. Therefore,Specific Aim 1 will focus on the identification of innate immune mechanisms that underlie both influenza sensitivity and Eritoran-mediated protection. We will take advantage of genetically modified mouse strains to dissectthe signaling pathways engaged. Whether TLR4 must be expressed on stromal and/or myeloid cells, the roleof virus-induced epithelial cell necroptosis in DAMP release, mechanisms by which non-TLR4 PRRs contributeto influenza resistance/susceptibility, and the possibility that TLR2/TLR4 dimerization is required for the hostresponse to influenza will be evaluated as novel potential mechanisms that can be exploited to enhance therapeutic efficacy. In Specific Aim 2, the therapeutic benefit of a novel IKKβ inhibitor, E6070 (Eisai, Inc.), againstinfluenza, alone or in the presence of current anti-influenza antiviral therapies, will be tested in cotton rats(CR), a second rodent species that permits analysis of ALI in response to infection by non-adapted human influenza isolates. Aim 2 will also compare Eritoran and E6070 in CR in a model of secondary staphylococcal(MRSA) pneumonia following influenza infection. Lastly, we will assess the relative effectiveness of Eritoranand E6070 for the ability to block ALI caused by other clinically important or biothreat pathogens associatedwith ALI in humans (e.g., Francisella tularensis, Streptococcus pneumoniae, Klebsiella pneumoniae, SARS-CoV and MERS-CoV), first in mice, and, if effective, in CR. These experiments will challenge the overarchingcentral hypothesis that TLR antagonists represent broad-based, therapeutic agents that mitigate pathologichost responses to multiple ALI-inducing priority pathogens.",2020,2022,UNIVERSITY OF MARYLAND BALTIMORE,52216,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies | Prophylactic use of treatments,2017 +C00866,3R01AI127799-04S1,Host dependence of influenza A virus reassortment,"The betacoronavirus SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemicthat has led to a public health emergency and social disruption on a scale not seen since theinfluenza pandemic of 1918. This new human pathogen is genetically, antigenically andphenotypically distinct from coronaviruses that circulate seasonally in humans and causesymptoms of the common cold. SARS-CoV-2 therefore presents many unknowns. To contributeto what we hope will be a broad effort on the part of the global infectious diseases community, wepropose herein to generate critical reagents that will facilitate research efforts and accelerateprogress toward filling critical knowledge gaps. Namely, we propose the construction of aninfectious molecular clone of the GA-83E strain of SARS-CoV-2 and derivatives thereofexpressing fluorescent and luciferase-based reporter genes. An infectious molecular clone, orreverse genetics system, is an extremely powerful tool which allows the generation of viralvariants carrying targeted mutations. This capability will accelerate progress toward criticalresearch goals. For example, the use of variant viruses carrying reporter genes can greatlystreamline identification of small molecule inhibitors and the titration of immune sera andmonoclonal antibodies. Similarly, the ability to introduce targeted mutations is invaluable in effortsto map antigenic sites, identify escape mutations, map determinants of transmission andvirulence, and identify viral features important for zoonotic potential. In sum, the reagent-generation effort outlined herein is designed to rapidly furnish the emerging SARS-CoV-2 fieldwith an essential tool of modern virology.",2020,2020,EMORY UNIVERSITY,127633,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C00867,3R01AI128775-07S1,COVID R PA-18-591 NOT-AI-20-031 Administrative Supplement to Integrated Exchange and Storage of Current- and Future-Generation Immunogenomic Data,"While little is known about the impact of host genetic factors on the risk for infection, morbidity and mortality inCOVID-19, current epidemiology reveals wide variation in disease course among confirmed cases of infectionthat is not fully explained by known comorbidities and other risk factors. Because of its pivotal role in the immuneresponse and long-established associations with disease phenotypes, Human Leukocyte Antigen (HLA)variation will likely be found to play a key role in COVID-19 outcomes. Understanding the role of HLA variationwill provide important insights relevant to the immunopathogenesis of COVID-19, while also informing vaccinedevelopment and potential immunotherapies (e.g. T-cell based therapies). Because the complexity and extremepolymorphism of the HLA region make consolidation, equivalency, analysis, and biological interpretation of HLAdata challenging, it is our view that a centralized resource that aggregates data from disparate sources andplatforms and provides well-curated bioinformatics and analytical tools will serve to accelerate discovery. Underthe parent grant we continue to develop a suite of tools and programs for the standardized analysis, collection,exchange and storage of immunogenetic data, and these tools are being widely adopted by the immunogeneticscommunity. This supplement request will allow us to apply these tools toward the development and applicationof a pair of web resources. The first will centralize access to COVID-19-related HLA data and HLA data-management and analysis tools, creating a knowledge base and technical resource for HLA and immunogeneticsresearch on the COVID-19 pandemic. As an initial step in advancing this vision, we have launched thehlacovid19.org website. The second resource will connect COVID-19 researchers and clinicians in need of HLAtyping services with the immunogenetics laboratories that can provide them. As an early step toward this goal,we have formed the COVID-19 HLA & Immunogenetics Consortium to unite the global community of HLA andimmunogenetics experts and leaders in support of these efforts, and harness the collective experience andexpertise of the HLA and immunogenetics community as part of the global effort to combat this pandemic.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,256339,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C00868,3R01AI130684-03S1,Supplement: Exploring the biology of O-acetyl sialic acids using stable synthetic mimics,"Exploring the biology of O-acetyl sialic acids using stable synthetic mimicsThis supplement request explores the possibility that sialoglycans may be co-receptors for SARS and COVID-19 virus spike (S) proteins, as is the case with MERS and other Coronaviruses (CoVs). Numerous virusesrecognize host cell surface glycans that terminate in sialic acids (Sias), a family of 9-carbon-backbonemonosaccharides present at very high densities on all vertebrate cell surfaces, and on most secreted proteins--particularly mucins that line and protect mucosal surfaces like the airways. Viral recognition of host sialoglycansis affected by Sia type, linkage to, and the structure of underlying glycans. Much of this natural diversity of Siasin viral infection remains underexplored. While many respiratory disease-causing viruses target Sias, Siarecognition is not currently reported in SARS-CoV-2, the COVID-19 pandemic virus. This stands in contrast tothe extensive literature on Coronaviruses and Sia receptors and is likely because a definitive human proteinreceptor (ACE2) for the virus S protein has been identified. A similar situation existed for the earlier MERS-CoVwhich had a well-defined receptor (DPP4) but was later found to also bind Sias via a different binding site. Giventhe very high Sia density in vivo, and the fact that Sias are the first contact of a virus on a mucosal surface, Siadiversity is likely to play important roles during natural infections. We hypothesize that airway Sias are alsorecognized by S proteins of SARS-CoV-1 and SARS-CoV-2. This supplement is based on strong foundationsbuilt by decades of studies of Sia diversity by the collaborating labs, including the parent project which addressesinstability of Sia O-acetyl modifications by synthesizing sialosides with corresponding N-acetyl analogs. Theurgent need for more careful exploration of Sia-binding functions of SARS and MERS will utilize a uniquesialoglycan microarray built up over years of collaboration between the labs. Additional diversity of humansialosides such as those with 9-O-lactyl Sia that have heretofore not been studied, but could be critical, will alsobe explored. We propose sialoglycan microarray studies of recombinant soluble external domains of S proteinsof MERS-CoV, SARS-CoV-1 and SARS-CoV-2 in comparison with human CoVs causing milder diseases, todetect Sia-dependent binding that has been missed so far. We will synthesize sialosides containing naturallyoccurring 9-O-lactyl-Sia and more stable 9-N-lactyl analogs and integrate these with the microarray and bindingstudies. Computational studies, including molecular dynamics simulation of binding free energies, willcomplement the array studies by predicting Sia variants that might bind, and modelling binding seen in arraystudies. These studies will generate new knowledge that may help to better understand viral infection,pathogenesis, and transmission from animals to humans and among humans. Additional viral epitopes criticalfor binding neutralization may be identified that could suggest novel preventative and/or therapeutic approachesto COVID-19. This project is therefore well suited to the urgency of the current pandemic situation. Informationlearned can also be applied toward the prediction and prevention of future epidemics and pandemics.",2020,2021,UNIVERSITY OF CALIFORNIA AT DAVIS,127633,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C00869,3R01AI132178-03S1,Broad-spectrum antiviral GS-5734 to treat MERS-CoV and related emerging CoV,"Zoonotic viruses, like filoviruses and coronaviruses (CoV), represent a continuous and growing threat to globalpublic health because they unpredictably emerge causing devastating outbreaks of pandemic disease. In the21st century, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratorysyndrome coronavirus (MERS-CoV) emerged from zoonotic pools of viruses, causing severe disease inhumans. MERS-CoV is endemic in camels in the Middle East with continuous new infections in humans.Although SARS-CoV is not currently a threat, several ""prepandemic"" SARS-like CoVs have been isolated frombats that replicate efficiently in human cells and are resistant to existing therapies. With the unpredictableoverlap of human and wild animal ecologies, the potential for novel CoV emergence into humans is highlyprobable. Currently, there are no approved antiviral therapies for any human CoV infection. Broad-spectrumCoV therapies that control known human and zoonotic CoV infections would address an immediate unmetmedical need and could counter future pandemic episodes. In partnership with Gilead Sciences, we havedemonstrated that the nucleoside prodrug, GS-5734, is highly efficacious in inhibiting multiple human andzoonotic CoV in vitro and SARS-CoV in vivo. The primary goal of our program is to accelerate the preclinicaldevelopment of GS-5734 and promote IND licensure for the MERS-CoV indication. To thoroughly evaluate thebreadth of antiviral activity and predict efficacy against future emerging CoV, we will also assess efficacyagainst a panel of CoV representative of family-wide genetic diversity, including prepandemic zoonotic strainspoised for emergence. Focusing on the highly pathogenic MERS-CoV, our unique partnership integrates: i)metagenomics and recombinant virus synthetic genome recovery, ii) primary human lung cell models, iii)cutting edge virology and biochemistry, iv) robust murine and primate models of human disease and v) state ofthe art metabolic and pharmacokinetic analysis. In Aim 1, we refine the pharmacokinetics, pharmacodynamicsand breadth of GS-5734 through efficacy and metabolism studies in various primary human cells with a diversearray of human and zoonotic CoV and through the evaluation of in vivo efficacy in murine and non-humanprimate models of MERS- and SARS-CoV. In Aim 2, we select for resistance against SARS-CoV and MERS-CoV, and determine the effect of resistance on virus replication, fitness and susceptibility to treatment. In Aim3, we determine if the mechanism of action of GS-5734 is a result of direct effects on viral RNA replicationand/or alteration of antiviral immunity via deep sequencing and single molecule RNA fluorescence in situhybridization of vehicle or drug treated infected cells and mice. We articulate a development strategy for broad-spectrum therapeutics that could be extended to a multitude of emerging viral pathogens threatening globalpublic health.",2020,2021,University of North Carolina at Chapel Hill,450462,Viruses,Not applicable,Not Applicable,Unspecified,Unspecified | Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00870,3R01AI132191-03S1,Rapid development of SARS-CoV-2 specific therapeutics that leverage virus specific RNA elements,"Our goal is leverage our recent insights into coronavirus B conserved RNA structures, and ourdiscovery of formulations for high efficiency lung delivery, into the rapid development of SARS-CoV-2 specifictherapeutics. Using a novel suite of computational technology tools, we have identified predicted RNAsecondary structures in regions conserved across coronavirus B genomes including SARS-CoV-2. We havealso identified two tandem predicted microRNA 191 (miR191) binding sites within the 5'-most such structure.In our current grant on influenza A virus (IAV), we identified an RNA secondary structure conserved across allIAV isolates that is essential for in vitro packaging and in vivo disease, then designed short highly stable lockednucleic acid (LNA) oligonucleotides to bind and distort this RNA packaging signal, and demonstrated that asingle dose of our lead LNA can a) provide immediate 100% protection for over 14 days from a lethal inoculumof IAV, b) provide 100% survival when administered 3 days after a lethal IAV inoculum, and c) while sufficientlyattenuating the infection, enable the subsequent development of high level immunity. Moreover, we have alsorecently discovered that empty deproteinized pollen shells represent an outstanding vehicle for delivery ofLNAs to the lung with much greater efficacy and tolerability than current formulations for nucleic acid delivery.We now hypothesize that 1) our identified RNA secondary structures in SARS-CoV-2 represent idealcandidate targets for disrupting the virus lifecycle, via structure-specific LNAs; 2) the miR191 binding siteswithin the 5'-most conserved RNA secondary structure reflect an essential mechanism for regulatingtranslation of corona B viruses that is amenable to targeting by specifically designed LNAs; 3) our noveldeproteinized pollen formulation represents an ideal means of delivering such LNAs to both prevent and treatestablished SARS-CoV-2 infections. We will test these hypotheses via the following specific aims that are to: 1)Determine which LNA gapmers from a screening panel synthesized against our identified conserved RNAsecondary structure targets are most disruptive to the latter's integrity, as assessed by SHAPE, REVI, andMutate-and-Map; 2) Refine the sequence (total LNA length, fine nucleotide target position, and length of singlestranded DNA gapmer) of the top performing LNA and test a panel of LNA analogs to identify the most potentdisrupter of targeted SARS-CoV-2 conserved RNA secondary structure; 3) Determine the effect of LNAsdesigned to sequester miR191 in cells transfected with a SARS-CoV-2 5' terminal RNA segment linked to aluciferase reporter; 4) Determine the effect of the identified lead LNAs (targeting conserved SARS-CoV-2 RNAsecondary structure, and sequestering miR191) on cells infected with SARS-CoV-2 in vitro, and in vivo whendelivered intranasally by current lung-targeting transfection reagent (i.e.JetPEi) vs. pollen shells to SARS-CoV-2-infected mice. Successful accomplishment of our aims will yield proof-of-concept for an exciting new class ofanti- SARS-CoV-2 RNA therapeutics within the short time frame of this proposal.",2020,2021,STANFORD UNIVERSITY,127633,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C00871,3R01AI132404-03S1,REGULATION OF MEMORY T CELL TRAFFICKING BY CORE 2 O-GLYCAN SYNTHESIS,"The current COVID-19 pandemic is a global health emergency, causing severe respiratory disease requiringhospitalization and even death in a significant proportion of the Human population. Although therapeuticintervention including novel pharmaceuticals or the passive transfer of immune serum from recovered patientscould provide short-term relief in mortality and morbidity, the development of a successful vaccine willultimately be required to prevent the continued spread and seasonal recurrence of this disease within theHuman population. However, very little is known about either the quality of adaptive immune response or theviral antigen targets that are necessary to prevent the infection. Here we propose to evaluate a novelvaccination approach recently developed in my laboratory that we will now apply to SARS-CoV-2. Specifically,we will generate Vaccinia virus (VacV) vectors expressing the SARS-CoV-2 Spike (S) protein that have beenengineered to targeted the S protein for MHC-II presentation. Overall, this study will evaluate whether VacVexpressing SARS-CoV-2 S protein could be a potential vaccine candidate and whether the ""immunogenicity"" ofthe S protein can be enhanced by targeting the protein for MHC-II presentation.",2020,2021,OREGON HEALTH & SCIENCE UNIVERSITY,381463,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +C00872,3R01AI132774-03S1,COVID Immunophenotyping Study,"This application is being submitted to PA-20-135 in accordance with NOT-AI-20-034. We are requesting anemergency supplement to R01AI32774 ""Mechanisms of IL-6 mediated T cell pathogenesis in autoimmunity""(PI: Jane H. Buckner). This supplement will directly address the NOT-AI-20-034 research area of interest""Identification and evaluation of the innate, cellular and humoral immune response to SARS-CoV-2infection....."". Importantly, the proposed work is part of the NIAID Immunophenotyping assessment in aCOVID-19 Cohort (IMPACC) study tasked with performing longitudinal immunophenotyping from 1,000subjects with COVID-19. For each subject, among other assays, transcriptomic profiling will be done onperipheral blood, nasal swabs and endotracheal aspirates at six different time points. Specific to theemergency supplement requested here, we will be responsible for performing both the bulk host mRNA-sequencing (RNA-seq) and PCR quantification of viral nucleic acid from SARS-CoV-2 for each of the ~6,000anticipated nasal swab samples. In addition, we will perform a pilot study on 60 nasal swab samplesassessing the potential utility of metagenomic sequencing on these samples to consider it in a larger scale inthis cohort. All work will be done in close coordination with NIAID, University of California, San Francisco(endotracheal RNA-seq), Emory University (blood RNA-seq), and Icahn School of Medicine at Mount Sinai(virology) core sites.",2020,2021,BENAROYA RESEARCH INST AT VIRGINIA MASON,381463,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations | Immunity",2020 +C00873,3R01AI134236-03S1,The Role of Group 3 Innate Lymphoid cells (ILC3) in Tuberculosis,"Over the past three months, COVID-19 has emerged as a major pandemic with over ~ 1.9 million productiveinfections and ~100,000 deaths due to infection with the novel Coronavirus SARS-CoV-2, a viral pathogenwhich is highly infectious and pathogenic. This is particularly true in the elderly and people withimmunocompromising conditions who are exhibiting acute respiratory distress syndrome at a greaterfrequency. Unfortunately, no known cures and vaccines exist. Worse, there were no well-characterized animalmodels of SARS-CoV-2 infection and COVID-19 disease till recently. With the limited information on hostinnate immune responses, early reports implicate a role for inflammation in mediating COVID-19 disease. Asan logical extension of ongoing work on innate immune responses in the lung on the parent grant, wehypothesize that similar to tuberculosis (TB), control of SARS-CoV2 will correlate with accumulation of innatelymphoid cells including NK cells in the lung, while inflammation and increased disease will be associated withmyeloid cell accumulation. To test this hypothesis, we will utilize recently acquired banked lung samples from anovel rhesus macaque model of SARS-CoV-2 infection/COVID-19 disease developed at the SouthWestNational Primate Research Center (in collaboration with Deepak Kaushal Lab, Co-I on parent grant). Thesenew results from the NHP model indicate that rhesus macaques develop signs of human COVID-19 diseaseincluding pyrexia, dysregulation of complete blood cell counts indicative of viral infection, acute stress markers,and experience cough and weight-loss. This is accompanied by high viral loads in bronchoalveolar lavage(BAL) and lungs, and pneumonia is detected by CT scan as well as grossly at necropsy. Single cell RNAsequencing (scRNA-seq) is just beginning to be applied to the immune system in animal models and humansin both healthy and diseased states. The application of scRNA-seq to COVID-19 samples from macaques isparticularly well-suited, as the immune cells infiltrating the lung that may play roles in the disease are diverse,including virtually all types of lymphocytes (ILCs, CD4+ T cells, CD8+ T cells, γδ T cells, NK cells, B cells) andseveral myeloid cell types (monocytes, macrophages and potentially dendritic cells (DCs) and neutrophils(PMNs)). Within each of these subtypes, further heterogeneity exists in terms of cytokine production andtranscription factor expression, such that each subtype may demonstrate further heterogeneity. BecausescRNA-seq can define the transcriptomic heterogeneity of a complex community of cells and assign unbiasedidentity classifications to cell populations, it is optimally suited for application to the study of complexinflammatory disease such as TB and COVID-19. The data obtained and its computational analysis willdelineate the nature of inflammation, especially the role of innate cells such as NK cells and ILCs in COVID-19mediated inflammation. These studies will create new opportunities for identifying therapeutic targets forcontrol of pan-epidemics such as TB and COVID-19.",2020,2022,WASHINGTON UNIVERSITY,309206,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00874,3R01AI134907-03S1,Development of reverse genetic systems and mouse model for SARS-CoV-2,"The recent epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused globalpublic health emergency. Rapid response to disease control and countermeasure development is a public healthpriority. Reverse genetic systems and animal models are essential tools for studying viral replication,pathogenesis, vaccine development, and antiviral discovery. The goals of this supplement project are to (i)establish the reverse genetic systems and (ii) generate a mouse pathogenesis model for SARS-CoV-2.",2020,2023,The University of Texas Medical Branch at Galveston,309206,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2018 +C00875,3R01AI134907-03S2,"A High-Throughput Platform for COVID-19 Serodiagnosis, Vaccine Evaluation, and Drug Discovery","In response to the current COVID-19 pandemic, it is of paramount importance to rapidly diagnoseinfections and to develop countermeasures. This project aims to build a high-throughput platformfor rapid COVID-19 serodiagnosis, vaccine evaluation, and therapeutics development.",2020,2021,The University of Texas Medical Branch at Galveston,699894,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics,2020 +C00876,3R01AI135270-02S1,Structural and Functional Analysis of the Coronavirus Spike Protein Fusion Peptide,"Enveloped viruses access their host cells by binding to receptors on the plasma membrane and then undergoingfusion with the host membrane. Both binding and fusion are mediated by a specific viral ""spike"" protein that istypically primed for fusion activation by proteolytic cleavage to expose the fusion peptide. Coronavirus fusionspike protein (CoV S) is a complex biomolecular machine that has a novel fusion peptide with has a great dealof inherent flexibility in its fusion reaction. This is exploited by these viruses in their diverse entry pathways andis a primary determinant of viral tropism. We have pioneered the concept that that the proteolytic cleavage eventsin S that lead to membrane fusion occur both at the interface of the receptor binding (S1) and fusion (S2) domains(called S1/S2), as well as adjacent to a structurally and functionally novel fusion peptide within S2 (called S2').Thus, there are notable differences between CoV S and most other class I fusion proteins including: 1) that theproteolytic events liberating the fusion peptide are diverse, and 2) that the fusion peptide itself is atypical insequence compared to other fusion peptides, containing a mixture of important hydrophobic and negatively-charged residues, and may represent a larger than normal fusion ""platform"" instead of a defined ""peptide"". Thusfusion peptide activity is likely controlled by reorganization of the fusion platform, based on both hydrophobic(i.e. lipid-binding) and ionic (i.e. Ca2+ and pH) interactions. Despite the recent availability of two S structures,there remains a very limited mechanistic understanding of membrane fusion for the CoV family, or any structuralinformation to correlate structural biology aspects of S to its function in membrane fusion. This information iscritical to understanding viral pathogenesis and CoV emergence into the Human population. We propose todevelop a panel of monoclonal antibodies to the SARS-CoV-2/COVID-19 fusion peptide that will be used as toolsto understand the fusion mechanism of coronaviruses, and which will be integrated into our biophysical,biochemical, and in vivo approach to study the unique cleavage-activated regulation of CoV S protein. Theseantibodies will also provide a platform for development of novel broadly-acting therapeutic antibodies for SARS-CoV-2 and other coronaviruses. Moving the field forward with these innovative studies will provide criticalknowledge about CoV entry and tropism needed to safeguard human health from an emerging pathogen likelyto cause severe outbreaks, and for which few or no medical countermeasures exist.",2020,2022,CORNELL UNIVERSITY,309206,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00877,3R01AI136962-03S1,"Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci: IL33, IL1RL1, and GSDMB - COVID 19 Supplement","This is an administrative supplement to the parent R01 ""Understanding the Molecular Genetic Mechanisms ofAsthma Risk Loci: IL33, IL1RL1, and GSDMB,"" which focuses on understanding how genetic polymorphismsalter epithelial secretion of the IL-1 family cytokine, IL-33. This supplement entitled ""Clash of Titans:Understanding the Airway Epithelial Interferon and IL-1 Response to SARS-CoV-2 Infection,"" addresses acritical need during a global pandemic. Our hypothesis is that a key virulence factor in the SAR-CoV-2 virus,the E protein, triggers IL-1B secretion from epithelial cells in a gasdermin and caspase dependent manner.That IL-1 secretion acts in an autocrine fashion, to inhibit critical interferon responses that are required toconstrain the virus to the upper airway and prevent lower airway infection. The proposal allows our laboratoryto use genetically altered cell lines that we generated as part of the parent grant to quickly study the balance ofinterferon and IL-1 responses of the airway epithelium to SARS-CoV-2 infection and test commerciallyavailable drugs that block caspases or IL-1 signaling to inhibit viral replication. This proposal seeks to rapidlytranslate our current understanding of airway epithelial cell biology to address a critical need for therapeuticsagainst the SARS-CoV-2 virus which has currently infected more than a million people worldwide and killedover 60,000 in less than 4 months.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,309206,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00878,3R01AI137276-02S1,Mechanisms of antibody-dependent enhancement of SARS-CoV-2 infection,"The ongoing COVID-19 pandemic represents a public health emergency of global concern, due to the high levelsof morbidity and mortality, as well as the ease of transmission. Intensive research efforts are currently focusedin the development of antibody-based therapeutics that would neutralize SARS-CoV-2 and provide robustantiviral activity. In addition, several vaccine candidates are currently being tested, as an effort to provide long-lasting immunity against SARS-CoV-2. However, a major concern about the safety of these approaches stemsfrom the capacity of antibodies -either administered passively or elicited upon vaccination- to enhance viralinfection, a phenomenon that is termed as antibody-dependent enhancement (ADE). Although ADE has beenprimarily demonstrated for flaviviruses, like dengue, it is unknown whether this phenomenon also extends tocoronaviruses. Like dengue disease, COVID-19 patients exhibit a wide range of clinical disease severity, rangingfrom asymptomatic to severe symptomatic disease, which is often fatal. This suggests that host immune factorslikely determine disease susceptibility and are critical for progression to severe disease. Additionally, SARS-CoV-2, the causative agent for COVID-19, shares high degree of sequence similarity with other human and batcoronaviruses, including SARS-CoV and MERS-CoV. Similar to what has been shown for dengue, it is likely thatpre-existing immunity against other coronaviruses might predispose for SARS-CoV-2 infection and developmentof severe COVID-19 disease. Likewise, active or passive immunization against SARS-CoV-2 might increase thesusceptibility to infection with other coronaviruses via the presence of non-neutralizing, cross-reactive antibodies.Although there is limited evidence on the capacity of anti-SARS-CoV-2 antibodies to mediate ADE, several priorstudies on SARS-CoV have provided some preliminary evidence that under specific conditions, anti-SARS-CoVantibodies might enhance infection of FcγR-expressing cells. Given the ongoing clinical development efforts forantibody-based therapeutics and vaccines to control SARS-CoV-2 infection, it is important to assess whetheranti-SARS-CoV-2 antibodies have the capacity to mediate ADE and if so, determine the precise molecularmechanisms and the role of FcγRs in this process. Our proposed studies aim to: (i) determine the ADE activityof IgG antibodies purified from recovered COVID-19 patients with variable degree of disease severity, (ii)generate and evaluate the ADE activity of anti-SARS-CoV-2 and anti-SARS-CoV mAbs with variable cross-reactivity and neutralization potency, and (iii) compare the ADE activity of Fc domain variants of these mAbs withselectively enhanced binding to specific human FcγRs to determine the role for human FcγRs in mediating ADEactivity. We anticipate that these studies will address a significance safety concern about the capacity ofantibodies to mediate ADE of coronaviruses, accelerating our efforts for the development of vaccine ortherapeutic interventions for the control of SARS-CoV-2 infection.",2020,2021,ROCKEFELLER UNIVERSITY,309206,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00879,3R01AI138709-03S1,Characterizing the broad antibody response to HIV superinfection,"The greatest hope for an end to the COVID19 pandemic caused by SARS-CoV-2 is a vaccine and/orantibody therapy. At this point, we know little about protective immunity to SARS-CoV-2, including whichepitopes are the major target of the antibody response to this virus and whether antibodies to specific epitopesimpact outcome. Advancing our understanding of SARS-CoV-2 immunity is critical not only for informingvaccine design, but also for understanding the epidemiology and spread of SARS-CoV-2, including amongasymptomatic individuals. There is considerable focus on targeting the region of the Spike protein that interactswith the receptor, which has also been a focus of HIV vaccine efforts for more than three decades with limitedsuccess to-date. Thus, given the urgency due to this pandemic, multiple approaches are warranted tocomplement this approach. We propose comprehensive profiling of the antibody response to SARS-CoV-2,which has the potential to detect both neutralizing and non-neutralizing antibody responses to all the proteinsin the virus. For this purpose, we will develop novel methods based on creating custom Coronavirus (CoV)phage display peptide libraries and using immunoprecipitation and deep sequencing to comprehensivelyexamine the antibody response to SARS-CoV-2 in a high-throughput manner. Using this platform, we willdevelop and test custom libraries that encode all seven CoV clades, including genetic circulating variants andpeptides spanning all viral proteins. This method will allow us to simultaneously detect antibodies to all CoVs ina person's plasma, enabling the detection of the specific responses to SARS CoV-2 infection as well asproviding insights on any interactions between common CoV and SARS-CoV-2 infections, be they protective orenhancing. We will also develop libraries of SARS-CoV-2 proteins that have mutations to all possible aminoacids at every possible amino acid using an approach we pioneered called Phage-DMS. We have validatedPhage-DMS as a tool to define key amino acids residues of epitopes and pathways of escape from antibodies.We propose to collect and compare convalescent plasma from verified cases of SARS-CoV-2, including thosewith severe symptoms, moderate symptoms and very mild symptoms as well as uninfected controls. Theinformation gained from these studies will help identify the peptide sequences that define the epitopes targetedby antibodies in response to SARS-CoV-2 infection and those that distinguish SARS-CoV-2 infection fromother CoV infections. We also hope to identify the antibody responses across the entire CoV genomes thatcorrelate with outcome, including specific responses to SARS-CoV-2 as well as any interacting effects ofresponses to other CoVs.",2020,2023,FRED HUTCHINSON CANCER RESEARCH CENTER,309206,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00880,3R01AI141003-03S1,Longitudinal Immunological Impact of SARS-CoV-2 Infection,"SARS-CoV-2 disease has recently become a major pandemic with significant global morbidity and mortality.Several key questions regarding the durability of immune responses to SARS-CoV-2 remain unanswered, suchas how long protective humoral and adaptive immunity persist following mild to more severe disease, andwhether or not the immune response may lead to longer-term protection from re-infection. As a result, there isurgent need to develop long-term, longitudinal cohorts that include a wide spectrum of SARS-CoV-2 infectionseverity and appropriately matched uninfected controls to study such questions. As a result, we initiated theLong-term Impact of Infection with Novel Coronavirus (LIINC) study leveraging our expertise at UCSF withlongitudinal cohort design and implementation for HIV and other infections, to identify and collect large-volumes of peripheral blood and saliva during frequent intervals starting during the early convalescent period.Building on our strong collaborative expertise in cohort implementation, virology and immunology, we willrecruit and characterize adults with a range of initial SARS-CoV-2 disease severity (asymptomatic to severe)and matched, uninfected controls. We have two short-term, high-impact objectives that we expect to addressrapidly, once funding is secured. First, we will obtain, process, and rapidly distribute large numbers of PBMCsand large volumes of plasma, serum and saliva for collaborative research to improve SARS-CoV-2 diagnosisand treatment. We expect to achieve this objective rapidly as we have an existing protocol, consent process,database and all of the required SOPs. We also have an established referral network already in place andexpect to rapidly enroll the cohort given intense community interest. Leveraging our nearly 20 year history, wehave designed a protocol and informed consent process that will allow us to rapidly support academic groups,foundations, and biotechnology and pharmaceutical companies to develop diagnostics and therapies. Second,using an extensive team of local investigators, we will characterize the establishment and decay adaptive andhumoral immune response to SARS-CoV-2. More specifically, our aims are to expand the LIINC cohort tocollect large volumes of plasma, serum and saliva at frequent intervals from early disease convalescence (21days following initial symptoms) to 24 months after recovery, determine the impact of SARS-CoV-2 infection onviral-specific CD4 and CD8 T cell responses up to 24 months following onset of symptoms, and define thelong-term kinetics of the antibody response and the duration of protective immunity following infection withSARS-CoV-2. Together, results from our studies would have implications on duration of protective immunityand provide key information on immunotherapy and vaccine development.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,309206,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00881,3R01AI141327-02S1,SARS-CoV-2 polymerase inhibitor screening,"Coronavirus disease 2019 (COVID-19) is an emerging global pandemic caused by the severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2). COVID-19 is imposing a tremendous public health threat, with novaccines and therapeutic agents against SARS-CoV-2 currently available. This novel single-strandedenveloped RNA virus is the seventh known human coronavirus. SARS-CoV-2 is unlike the other coronavirusesknown to cause the common cold (229E, OC43, NL63, and HKU1), but similar to the zoonotic severe acuterespiratory syndrome coronavirus from 2002 and the Middle East respiratory syndrome coronavirus from 2012.Pneumonia and respiratory failure are the reported clinical complications of the infected by thesecoronaviruses.While vaccines and monoclonal antibodies against SARS-CoV-2 are in development, a number ofinvestigational therapies are currently being considered and tested, including repurposed clinically approveddrugs targeting SARS-CoV-2 cell entry and replication. For example, viral polymerases have been majortherapeutic targets, as seen in multiple drug discovery successes targeting various viral pathogens (e.g., HIV-1, HCV, and HBV). In fact, the chemistry team of our Center for Drug Discovery (CDD) at Emory University (ledby Dr. R. F. Schinazi), have previously discovered several nucleoside/nucleotide viral polymerase inhibitorsincluding lamivudine (3TC) and emtricitabine (FTC) to treat HIV, as well as sofosbuvir to cure HCV. Building onthis successful mechanistic strategy, our current strategic approach for SARS-CoV-2 is to target its viral RNA-dependent RNA polymerase with specific nucleoside compounds that could potentially inhibit viral replication.In this competitive revision application, we have chosen a highly selective and chemically diversenucleoside/nucleotide RNA polymerase inhibitor library, which consists of 200 compounds. We havepreviously established a safe toxicity profile for this set of compounds using our in vitro toxicity screening assaythat consists of a panel of key cell-lines including human primary cells. Our goal is to investigate the antiviralefficacy of each of these compounds by employing our established in vitro SARS-CoV-2 virus culture and viralassay system.",2020,2023,EMORY UNIVERSITY,309206,Other,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C00882,3R01AI141953-02S1,Clinical Sample Collection COVID19 Patients to Align with NIAID National Study,"The NIAID national protocol intends to enroll at least 1000 COVID19 patients in a study designed to track infectedpatients through tracking, over time, their immune responses, viral load, and a variety of multi-omic analytes thatcan provide deep insights into how infection by SARS-CoV-2 is revealed in host defense responses and disease-perturbed networks. At the heart of this study is the establishment of high quality biorepositories that can beused to quantitatively assess viral load, quantitatively interrogate viable PBMCs, and permit direct comparisonsbetween different patients and different time points of disease progression. The nature of the infection, withhighly differential patient outcomes, will eventually require significant computational efforts that can account forconfounding factors such as co-morbidities, the influence of various therapies that are being broadly tested inthese patients, etc. It will also almost certainly require all 1000 projected patients, if not more, to resolve someof the most outstanding and urgent clinical questions. However, all of these results rely on establishing highquality biobanks, resource sharing, and data sharing. This is an area in which the ISB has deep expertise andis excited to contribute. The ISB and SMC launched a joint study designed to enroll 200 COVID19 patientsaround 3/20/2020. That study has overlap with the NIAID protocol and shares a common set of over-archinggoals. Here we propose to increase that overlap and to make that accruing biobank of COVID19 patientspecimens and associated characterization data a national resource through inclusion in the NIAID protocol.",2020,2022,INSTITUTE FOR SYSTEMS BIOLOGY,309206,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Disease pathogenesis",2020 +C00883,3R01AI141953-02S2,Site Specific Immunophenotyping Assays of COVID19 Patients to Align with NIAID National Study,"The NIAID national protocol intends to enroll at least 1000 COVID19 patients in a study designed to track infectedpatients through tracking, over time, their immune responses, viral load, and a variety of multi-omic analytes thatcan provide deep insights into how infection by SARS-CoV-2 is revealed in host defense responses and disease-perturbed networks. At the heart of this study is the establishment of high quality biorepositories that can beused to quantitatively assess viral load, quantitatively interrogate viable PBMCs, and permit direct comparisonsbetween different patients and different time points of disease progression. The nature of the infection, withhighly differential patient outcomes, will eventually require significant computational efforts that can account forconfounding factors such as co-morbidities, the influence of various therapies that are being broadly tested inthese patients, etc. It will also certainly require both broadly available immune characterization tools that can beapplied on all patient samples, but also specialized tools that can be used to inform the interpretation of thegeneral analytics. In this project, we propose to integrate two sets of immune cell characterizations into thenational NIAID effort. Those characterizations include single cell, functional phenotyping of select immune cellclasses via an analysis designed to quantitate the levels of 35 secreted proteins from up to 2000 single cells ofa given immune cell type. The second characterization is based upon reducing proteins from the SARS-CoV-2into peptide antigen-major histocompatibility complex (pMHC) libraries that can be used to identify SARS-CoV-2 antigen-specific CD8+ and CD4+ T cell populations from isolated, viable PBMCs. These assays provide deepand complementary information that will significantly inform the interpretation of the immune phenotyping assaysthat constitute the COREs of the NIAID study.",2020,2022,INSTITUTE FOR SYSTEMS BIOLOGY,309206,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +C00884,3R01AI143875-02S1,Population-based survey of SARS-CoV-2 infection and immune response,"To have an optimal response to the COVID-19 epidemic, it is important to understand the proportion of adultsin the United States may have the virus that causes COVID-19, and how many have had it in the past and mayhave immunity. Currently available data are limited because the impact of asymptomatic and mildlysymptomatic cases is unclear and many people are unable to access a test due to rationing, or may beotherwise unwilling to go for testing or care. This study will address this problem by conducting a nationalprobability sample, where each address may be selected by chance, to develop estimates of the proportion ofadults in the United States that are infected with the virus that causes COVID-19, and the proportion that hashad the disease in the past and may now have immunity. We will use home-based testing techniques tofacilitate participation in this national study. We will also use surveys to better understand participants in oursample. With these estimates, we will conduct disease modeling to understand different scenarios of theepidemic. We will also develop a website to provide information and data to the public.",2020,2021,EMORY UNIVERSITY,5429240,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +C00885,3R01AI145147-02S1,A novel mouse model for SARS-CoV-2 infection and therapeutics screening,"Animal models of COVID-19 will play a critical role in developing and testing novel vaccines and therapies forthis disease, but a very limited number of models are currently available, and they suffer from substantiallimitations. The SARS-CoV-2 virus uses human ACE2 to bind to cells, and the host TMPRSS2 protease toprime the viral spike proteins for entry. Three mouse strains expressing human ACE2 as a transgene exist-only one of which is being prepared for distribution in the US and is in high demand under the currentcircumstance. Furthermore, concerns exist about aberrant expression of human ACE2 in these mice, given thelack of normal regulatory elements, and none of the ACE2 transgenic strains express the human TMPRSS2protease, thus cannot be used to assess therapeutic strategies that target the protease. We propose toemploy a novel and rapid gene replacement strategy that we have pioneered, to generate ACE2 andTMPRSS2 gene replacement mice. Our BSL3 experienced team will infect these mice with SARS-CoV-2 inorder to determine if they display the expected viral replication, interstitial pneumonia, inflammatory cytokinestorm, and antibody responses that characterize human COVID-19 disease. Importantly, these mice will beimmediately sent to our partners at Jackson Labs (JAX) for rapid expansion and world-wide distribution.",2020,2021,UNIVERSITY OF MINNESOTA,525989,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C00886,3R01AI145687-02S1,"Structures of initial CD4 engagement with pre-fusion, closed HIV-1 Envelope trimer and early CD4-induced conformational changes required for infection","Targeting early metastable intermediates of the SARS-CoV-2 spike for vaccine and therapeutics developmentThe ongoing global pandemic of the novel SARS-CoV-2 presents an urgent need fordevelopment of effective preventative and treatment therapies. The viral-host cell fusion (S) protein spike is aprime target for such therapies owing to its critical role in the virus lifecycle. The S protein is divided into tworegions: the N-terminal S1 domain that caps the C-terminal S2 fusion domain. Binding to host receptor via theReceptor Binding Domain (RBD) in S1 is followed by proteolytic cleavage of the spike by host proteases. Thisleads dramatic conformational transitions resulting in S1 shedding and exposure of the fusion machinery in S2,culminating in host-cell entry. Class I fusion proteins such as the CoV S protein that undergo largeconformational changes during the fusion process must, by necessity, be highly flexible and dynamic. Indeed,cryo-EM structures of the SARS-CoV-2 spike reveal considerable flexibility and dynamics in the S1 domain,especially around the RBD that exhibits two discrete conformational states - a ""down"" state that is shieldedfrom receptor binding, and an ""up"" state that is receptor-accessible. The overall goals of this study are to useour robust, high-throughput computational and experimental pipeline to define the detailed trajectory of the""down"" to ""up"" transition of the SARS-CoV-2 S protein, identify early metastable intermediates in the fusionpathway, and exploit their structures and dynamics for identifying drug and vaccine candidates that targetSARS-CoV-2. A wealth of structural information on CoV spike proteins, including recently determined cryo-EMstructures of the SARS-CoV-2 spike, provides a rich source of detailed data from which to begin preciseexamination of macromolecular transitions underlying triggering of this fusion machine. The scientific premiseof this study is that understanding the structural dynamics and early transition kinetics of mobile regions of theSARS-CoV-2 spike will allow optimal control of vaccine and drug responses, and facilitate the development ofnovel antiviral drugs and protective vaccines. At the culmination of this study, we expect to have determinedstructures of multiple ""down"", ""up"", and intermediate states of the SARS-CoV-2 S protein. Together, thesestudies will provide important atomically detailed structural and mechanistic information for exploitation invaccine and therapeutics design.",2020,2022,DUKE UNIVERSITY,732990,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C00888,3R01AI146779-01S1,Epitope focusing by molecular grafting of subdominant epitopes to achieve a universal-influenza vaccine,"There is urgent need for the development of effective countermeasures against the newly emerged novelcoronavirus or ""nCoV"" (also known as COVID-19). The development of a ""universal"" coronavirus (CoV)vaccine would not only be effective against COVID-19 but, in theory, would protect against future,potential pandemic CoV strains. The pathway to such a vaccine will likely focus on the design of novelimmunogens that elicit broadly neutralizing antibodies to conserved viral epitopes, such as the receptorbinding site (RBS). Here we leverage our structure-based, ""resurfacing"" and glycan engineeringimmunogen design approaches for a universal influenza vaccine and extend it to COVID-19. Our ongoingstudies for influenza demonstrate that our resurfaced, heterochimeric immunogen approach substantiallyincreased the overall frequency of elicited RBS-directed responses and our glycan engineering approachcould effectively focus the immune response to a novel, conserved influenza hemagglutinin epitope; weenvision that implementing comparable immunogen design approaches for COVID-19 specificallyfocusing to its receptor-binding interface epitope would yield similar results. We intend to use thisAdministrative Supplement to generate preliminary data to show the efficacy of our approach for aCOVID-19 vaccine, and to optimize the vaccine regimen in the murine model; the data generated herewill form the basis for future studies for a universal CoV vaccine.",2020,2022,MASSACHUSETTS GENERAL HOSPITAL,150398,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Vaccine design and administration,2019 +C00889,3R01AI148416-01S1,Epigenetic Priming of Inflammatory Genes in COVID-19: Insights into Pathogenesis and Prognosis,"The relatively high morbidity and mortality rates of the coronavirus disease 2019 (COVID-19) pandemic,caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), makes understanding specificrisk factors, pathogenesis and identifying effective therapies a top priority [1], [2]. Age is a general riskfactor, though there is high-variance in the clinical course of COVID-19 in middle-aged patients,including mortality rates over 1% among patients in their 50's [3], [2]. Further, more than one quarter ofnon-survivors in a Wuhan study have no co-morbidities [1]. Non-survivors had elevated serum IL-6, andfeatures of acute respiratory distress syndrome (ARDS) [1], [2]. These findings have provided rationalefor initiation of trials to explore therapeutic efficacy of IL-1R and IL-6R blockade in COVID-19 [4]. Instudying epigenetic control of inflammatory genes, we have found that key immune genes in bloodprogenitors are variably regulated by epigenetic poising across individuals, with variability across age anddisease states. Herein, we aim to reveal specific genes, and epigenetic states of these genes, that mayunderlie morbidity and mortality in COVID-19 through use of sensitive epigenomic methods recentlydeveloped by the lab. This work will illuminate features of SARS-CoV-2 susceptibility and pathogenesis,which is of the utmost importance if we are to develop effective therapies and patient managementstrategies in a timely manner.",2020,2022,Weill Cornell Medicine - Cornell University,309206,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C00890,3R01AI150246-01S1,The role of pattern recognition and autophagy in innate anti-bunyaviral immunity,"The current outbreak of the coronavirus in China (SARS-CoV-2) has spread rapidly. There are experimental drugswhich will be tested; however, there are no approved therapeutics or vaccines. Indeed, there are tests underway todetermine whether remdesivir, which was developed against filoviruses, can be repurposed against SARS-CoV-2infection. It would be transformative if we could identify additional small molecules that could be repurposed to treatthe outbreak of SARS-CoV-2 infection. Given that the goal of the parent grant (R01AI150246) is to discoverantivirals active against bunyaviruses, based on findings from cell based screening, and that we have broadexpertise in diverse viruses, we are applying for Supplemental funding (notice number NOT-AI-20-030, PA-18-035)to expand the scope of the existing grant to use the same methods (small molecule screening) to identify antiviraltherapeutics active against SARS-CoV-2 infection. We will screen two libraries of known bioactives to potentiallyrepurpose existing therapeutics. First, we will test a library of innate immune agonists (~100 PAMPs) for their abilityto block SARS-CoV-2 infection in human cells including airway cells. Second, we will screen another 'actionable'library that I have created as the Director of the High-throughput Screening core at UPENN. We created a library of~3000 drugs that includes ~1500 FDA approved compounds, ~1000 drugs in clinical trials and the remaining drugshave known targets. This library has been used for repurposing (as is being done with the Gilead drug remdesivirthat was originally developed against filoviruses) to more rapidly identify active therapeutics for future testing inhumans. We will also determine if any of our active antivirals act synergistically with remdesivir since this drug iscurrently under development for use against COVID-19. We expect to identify additional drugs with activity againstSARS-CoV-2.",2020,2022,UNIVERSITY OF PENNSYLVANIA,111910,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00891,3R01DA040488-05S2,RCT of a social-network oriented mhealth based intervention to increase access and adherence to HCV treatment and HIV viral suppression,"The SARS-CoV-2 (COVID-19) epidemic has been rapidly changing. Vulnerable populations, such as peoplewho use drugs (PWUD), are particularly susceptible both to severe COVID-19 illness as well as health andwell-being consequences associated with the secondary impacts of the COVID-19 epidemic.PWUD are at higher risk of COVID-19 due to high levels of comorbid health conditions and high incidence ofrespiratory impairment due to cigarette smoking. The health of PWUD are also influenced by social policiesand practices implemented as part of COVID-19 response strategies. For example, COVID-19 socialdistancing measures and hospital access restrictions may reduce PWUD's ability to obtain HIV, HCV, andother types of critical health and social services. Those who are on medication assisted treatment may be atrisk for treatment disruptions, and those who attend self-help groups such as NA and AA may be unable toattend meeting or see their sponsors. Engagement in COVID-19 prevention measures may also be moredifficult for PWUD. High rates of homelessness and unstable housing among PWUD, may prohibit their abilityto 'stay in place'. As they may have no place to stay. Unstable sources of income and effort to avoidwithdrawal symptoms may lead PWUD to more frequent interactions with others and less social distancing, aswell as more frequent sharing of injection equipment. As COVID-19 is a novel disease and massive socialchanges have been implemented, which have not been utilized since the influenza epidemic of 1918, there isscant literature to aid us in predicting the long and short-term impacts of COVID-19 among PWUD.Consequently, we propose to conduct a mixed methods study that would entail frequent (bi-weekly) qualitativeassessments of a sample of PWUD and a quantitative survey. We propose these frequent qualitativeinterviews as the situation may change rapidly depending on the epidemic dynamics.The parent grant (R01DA040488) is an RCT to improve HIV and HCV health outcomes and reduce HIV, HCV,and drug overdose risk behaviors among people who inject drugs (index participants) and their social networkmembers.",2020,2021,JOHNS HOPKINS UNIVERSITY,163364,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2015 +C00892,3R01DA044159-02S1,Testing of patient-centered e-health implementation model in addiction treatment,"Coronavirus (COVID-19) has disrupted the substance use disorder (SUD) treatment system, demanding anabrupt shift from in-person care to telehealth services. The transition to virtual care could permanently changeSUD treatment delivery. This shift is coinciding with COVID-19-induced social isolation and anxiety, whichcould increase substance use and mental health disorder severity. A common refrain in the treatment andrecovery field is that addiction is a disease of isolation; the cure is connection. To provide virtual treatment andthe connection so essential to recovery, many SUD treatment centers are launching virtual services without amethod for assessing how, where, and why virtual services are affecting their patients' quality of life and SUDrecovery. The ACHESS smartphone app is currently being used at 40 Iowa treatment sites in the parent study,""Test of a patient-centered e-health intervention in addiction treatment settings."" ACHESS offers a guide and amethod for assessing use of virtual services and an unprecedented research opportunity. From 3/3/20 to3/20/20, sign-ups for ACHESS in the parent study increased by 67% compared to the two prior weeks. Activityon the ACHESS app has nearly doubled in the same period! This supplement will address patient andorganizational factors because of their integral roles in providing virtual care and adopting patient-centeredtechnologies. The supplement will enhance ACHESS with new COVID-19 related features designed to helppatients comply with social distancing guidelines, cope with unprecedented social isolation, and access virtualservices and supports. The research will study how patients use ACHESS features, how organizations referpatients to the ACHESS, how they interact with patients in ACHESS, and the overall impact of the ACHESSfeatures. The supplement's research aims are: Aim 1a: Refine ACHESS to provide information, support, anddata on COVID-19, social distancing, adjusting to social isolation, and how to use virtual SUD services. Then,study how patients use existing ACHESS features before (for existing ACHESS services only), during, andafter the announcement of social distancing guidelines. Aim 1b: Assess how the enhanced ACHESS APPaffects anxiety, loneliness, and reported COVID-19 infections. Aim 2: Create ten case studies describing howagencies implemented and used COVID-19 enhanced ACHESS and how their patients used COVID-19enhanced ACHESS. This supplement's projected outcomes will help us understand how to design virtualrecovery systems to mitigate the effects of a pandemic and the resulting social isolation. The results will helpdesign a virtual recovery system that can be used in future emergencies and to address the on-goingchallenges of social isolation in society post-COVID-19.",2020,2023,UNIVERSITY OF WISCONSIN-MADISON,154983,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Policy research and interventions,2018 +C00893,3R01DA045473-02S1,A Structure-based Drug Discovery Effort to Combat COVID-19 and Future Outbreaks,"The coronavirus disease 2019 (COVID-19) pandemic that originated in Wuhan, China just a few months ago isadvancing at an incredible rate in the United States and the rest of the world. It is impacting everyone's lives,as well as crippling the global economy, health care systems, and more. The disease is caused by the SevereAcute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen, and it appears to exert its mostdevastating effects on people's respiratory and pulmonary systems although recent reports have also citedcardiac complications in otherwise healthy individuals. Based on analyzed data from confirmed cases in theUnited States between February 12th and March 28th, the CentersforDiseaseControlandPreventiondisclosed that people with substance use disorders such as those with histories of smoking, as well as thosewith diabetes, chronic lung disease, and heart disease may be at increased risk of developing severecomplications from COVID-19. Considering the prevalence of these health conditions in the United States, theglobal COVID-19 cases approaching 1 million at the time of this writing, the alarming COVID-19 projections forthe month of April, the likelihood that COVID-19 becomes seasonal, and the fast pace at which SARS-CoVpathogens evolve into forms with higher cross-species transmission and/or higher affinity for human receptors,theredoctorsagainstagainstis no doubt that the scientific world must mobilize to offer as many solutions as possible to help medicaland health care providers save lives. Among these solutions, are suggestions for new medicationsCOVID-19, considering repurposed or may not prove effectiveCOVID-19. against drugs in clinical trials mayIn this application, we propose to expand the range of potential medicationsthat currentlyCOVID-19 using a rational, structure-based drug discovery approach focused on the virus-receptor recognitionmechanism, which regulates its infection, pathogenesis, and host range.",2020,2022,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,169420,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2018 +C00894,3R01DA049644-01A1S1,"Ethno-epidemiology of HCV, HIV and Overdose associated with Drug Marketsand Drug Tourism","To respond to the burgeoning SARSCoV-2 epidemic, we propose to leverage the infrastructureof a new binational cohort of 600 people who inject drugs (PWID), as well as additional UCSDinvestigators who have expertise in analysis of social networks, microbiome, and geneticsequencing data to address the proposed aims:Aim 1. To determine the prevalence and correlates of subclinical and symptomatic SARSCoV-2infection among PWID within the SD/TJ border region.Aim 2. To determine the prevalence and correlates of SARSCoV-2 shedding in nasal secretionsand fecal specimens among PWID.Aim 3. To determine network features associated with cross-border transmission of subclinicalSARSCoV-2 infection among PWID.Aim 4: To use molecular epidemiology to determine the global migration of SARSCoV-2 betweenPWID in San Diego and Tijuana and factors associated with local and global dispersal.We will use social network surveys, microbiome analysis and full length SARSCoV-2 sequencingto characterize PWIDs' social network determinants of SARSCoV-2 infection, the influence of themicrobiome on shedding, and the viral genetic migrations within SD, TJ and beyond. Accurateestimates of subclinical infection of SARSCoV-2 and its risk factors are needed to informprevention, treatment, and public policy, especially in a cross-border context where borderclosures have already been implemented as a costly measure to curb transmission.",2020,2025,UNIVERSITY OF CALIFORNIA-SAN DIEGO,5429240,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C00895,3R01DA049843-01S1,Methamphetamine Use and HIV as Risk Factors for COVID-19,"Among men who have sex with men (MSM), there is a resurgent epidemic of methamphetamine (meth)and other stimulant use that fuels new HIV infections and compromises the benefits of HIV treatment asprevention. Although MSM living with HIV who use meth can achieve viral suppression, prior research from ourteam and others has documented that recent stimulant use amplifies immune dysregulation in treated HIVinfection. MSM living with HIV are also more likely to report amplified behavioral risk such as condomless analintercourse that increases risk for HIV acquisition and onward HIV transmission. The scientific premise of thisadministrative supplement is that co-occurring meth and HIV will create a double jeopardy for the novelcoronavirus (COVID-19) pandemic. In order to examine the potentially synergistic effects of meth and HIV forthe COVID-19 pandemic, we will enroll 200 MSM in a seroprevalence study testing for IgM and IgG antibodiesto the novel coronavirus (SARS-CoV-2). Using an intact groups design, participants will be enrolled based onmeth use (user versus non-user) by HIV status (positive versus negative). Among men living with HIV, onlythose who report an undetectable viral load will be enrolled. Among men who are HIV-negative, only those whoare not currently taking pre-exposure prophylaxis (PrEP) will be enrolled. There will be 50 participants enrolledper group: METH+HIV+, METH+HIV-, METH-HIV+, and METH-HIV-. The primary hypothesis is that thosewith co-occurring meth use and HIV (METH+HIV+) will display the greatest seroprevalence of SARS-CoV-2relative to meth or HIV alone (METH+HIV- or METH-HIV+) or controls (METH-HIV-). We will also examine theextent to which co-occurring meth and HIV are indirectly linked to higher SARS-CoV-2 seroprevalence viaalterations in gut-immune dysregulation, smoking behaviors, and decreased adherence to social distancingguidelines. This supplement will provide some of the first data regarding whether and how those with co-occurring meth use and HIV are more vulnerable to SARS-CoV-2 infection. This represents a crucial first stepto identifying high priority populations that will directly inform the development bio-behavioral interventions tomitigate risk for COVID-19. These findings will also inform targeted public health efforts to ""flatten thecurve"" of community-level SARS-CoV-2 transmission in this rapidly evolving COVID-19 pandemic.",2020,2024,UNIVERSITY OF MIAMI SCHOOL OF MEDICINE,5429240,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sexual and gender minorities,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity,2019 +C00896,3R01DC014463-05S4,"Patient reported outcomes, COVID-19 knowledge and perceived risks, and healthcare among deaf and hard of hearing adults in the U.S","Current widely used NIH-funded patient reported outcome measurement systems (PROMIS)include domains that assess global, physical, mental, and social health from the patient's perspective.PROMIS is heavily dependent on English, which is a serious barrier to DHH patients who use AmericanSign Language (ASL) and demonstrate low English proficiency. In 2015, PI Kushalnagar was awardedan R01 to address this knowledge gap through 1) linguistic and psychometric validation of PROMIS-Deaf Profile in ASL and 2) cross-sectional analysis of patient reported outcomes (PROs) in an U.S.sample of DHH adults who use ASL. We have added revised aims to address the urgent issues relatedto coronavirus. This revision application addresses an immediate need to create an online ASL/English surveyto quickly deploy and assess an underserved DHH population's knowledge/attitude toward physicaldistancing, self-perceived risk for COVID-19, patient-physician communication, and healthcare accessexperience. This study will also gather new data from key stakeholders that works with this population;and will be used to inform the correct interpretation of the quantitative findings from PROs and COVID-19 data. Together, using mixed methods approach, the team will integrate quantitative PROs andCOVID-19 data with stakeholder qualitative data to enlighten new findings and provide the necessaryfoundation for public health policy and program strategies aimed at improving human communication inDHH population.",2020,2021,GALLAUDET UNIVERSITY,179842,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Prognostic factors for disease severity | Approaches to public health interventions,2020 +C00897,3R01DC018075-01A1S1,Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain,"(Administrative Supplement)COVID-19 is a viral disease (SARS-CoV-2) that was declared a pandemic by the World Health Organization onMarch 11, 2020. The disease has negatively impacted the health of millions of people around the world and istaking a toll on the global economy. The disease has been particularly difficult to contain as it is highlycontagious, has a long incubation time (2-14 days) and many carriers of the virus are asymptomatic [1-2].Initial reports of the disease showed that the symptoms of COVID-19 are fever, fatigue, body aches andshortness of breath [3-4]. However, more recent reports have shown that many COVID-19 patients also losetheir ability to smell [5]. Furthermore, reports show that the patients who experience smell loss may otherwisebe asymptomatic suggesting that smell loss could potentially be an early indicator of COVID-19 in a subset ofthe population [5]. These recent findings highlight the importance of studying the relationship between smellloss and COVID-19 to better understand the mechanisms and symptoms of the disorder as well as its potentiallong term effects. The study proposed here will investigate: 1) the extent to which COVID-19 patients developsmell loss (anosmia); and 2) whether the early presence of anosmia can be used to predict the severity ofdisease. To invesitgate this urgent question, we will use the well-established 8-item ""Brief"" University ofPennsylvania Smell Identification Test (""B-SIT"") [6-9] to assess the olfactory abilities in patients with suspectedCOVID-19 infection who present to the COVID-19 external testing sites affiliated with the University ofPennsylvania.",2020,2021,UNIVERSITY OF PENNSYLVANIA,197357,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2020 +C00898,3R01GM122876-04S1,Competitive revision to - Methods to estimate the effect of intervention on the incidence and transmission of Tuberculosis,"The current pandemic due to Coronavirus Disease 2019 (COVID-19) has led to the unprecedented use of nonpharmaceutical interventions (NPI), including limiting travel, closing business and schools, and ordering peopleto shelter in place. While these extreme interventions are effective in slowing transmission of the disease, it isnot clear how they can best be implemented and how other local factors (such as population density, agestructure, timing in the outbreak, and smoking prevalence) might impact their efficacy. We are building a globaldatabase of these interventions in order to more carefully explore these questions and allow other researchersto use this data in their research. We will create models to better understand how NPI impact diseasetransmission and how the local context effects the impact of these NPI. We are working with colleagues in NYC,Spain, and Italy with more granular data to better explore these problems. We aim to develop a framework thatis applicable to widely available case notification data.As the disease spreads to vulnerable populations, such as people experiencing homelessness, persons livingwith HIV (PLWH) and TB, we anticipate that the impact on these populations will be more severe and with a higher force of infection. We will are involved in an effort to build a COVID-19 patient data warehouse at BostonMedical Center, the largest safety net hospital in New England. This will also include COVID-19 treatment andtesting data from Boston Healthcare for the Homeless. We will use this data to study the impact of COVID-19 onthese vulnerable populations. We will also leverage our strong relationships with collaborators in South Africa,the Philippines, and Ukraine, where the prevalence of these conditions is much higher, in order to better elucidatetransmission patterns and impact in the developing world. We will estimate the impact of potential treatmentdisruptions due to the pandemic response on HIV and TB populations.",2020,2022,BOSTON UNIVERSITY MEDICAL CAMPUS,307029,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Indirect health impacts,2017 +C00899,3R01GM130900-01A1S1,"Ebola modeling: behavior, asymptomatic infection, and contacts (2019-nCoV Admin Supplement)","We propose to use statistical methods we have used for Ebola virus disease forecasting in order toproject COVID-19 transmission at the state and municipal level, producing testable forecasts. Thesewill feature continuously updated estimates of the reproduction number (number of cases per case)and permit us to assess the benefits of current interventions (social distancing, school closure). We also propose to conduct a close analysis of the fraction of cases traceable to known cases.This statistic can be useful because it can indicate transmission through unknown routes or throughasymptomatic cases, but it can also be influenced by the efficacy of contact tracing itself. Manycases that would have otherwise occurred are caught and prevented by contact tracing and isolation.We will conduct network simulations to determine when large values of this presage epidemic growth(depending on the reproduction number, and timeliness and yield of contact investigation). Finally, we will use detailed network simulation to yield a pandemic preparation road maplooking into the future. Specifically, specific events (rate of increase of cases, large number ofuntraceable cases, cases in varying geographic areas) will yield specific actions (school closures,mass gathering abrogation) despite uncertainty in the mode of transmission. These detailed modelswill also be used for real time assessment of the timing and duration of school closure.",2020,2023,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,242000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease models | Disease transmission dynamics",2019 +C00900,3R01HL146206-02S1,Studies on the effects of colchicine on neutrophil biology in acute myocardial infarction,"The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease2019 (COVID-19), has resulted in a global pandemic. COVID-19 cases in the New York City (NYC) tri-statearea continue to rise exponentially and the region is now the epicenter of the crisis in the United States. InNYC alone, there are over 21,000 cases (~40% ≥40 years of age) as of March 26, 2020. Many symptomaticCOVID-19 patients have features of a cytokine storm and/or macrophage activation syndrome, includingelevated levels of interleukin (IL)-6. An overly robust local neutrophil influx may also contribute to the robustimmune response with associated severe cardiopulmonary complications, including acute respiratory distresssyndrome requiring mechanical ventilation and myocarditis with cardiogenic shock. Colchicine is a safe, well-tolerated anti-inflammatory agent that suppresses the activation of the NLRP3 inflammasome, thereby blockingconversion of pro-IL-1β to active IL-1β, which leads to secondary reductions in other cytokines including IL-6along with inhibition of macrophage activation. Colchicine also preferentially accumulates in neutrophilscompared with other inflammatory cells and inhibits chemotaxis, endothelial adhesion, and extravasation ofneutrophils at sites of endothelial or tissue inflammation. The effects of colchicine in preventing the cytokinestorm and/or macrophage activation syndrome that leads to clinical deterioration in COVID-19, however, is notknown. Colchicine is not known to inhibit acquired immunity, and is not contraindicated in patients withinfection.The COLCORONA study is a Canadian government-funded randomized trial of colchicine vs. placebo for 30days in 6,000 non-hospitalized subjects 40 years of age with COVID-19 diagnosis and at least one high-riskcriterion. This proposal leverages the COLCORONA Trial infrastructure and pragmatic study design with virtualconsent, randomization, and follow-up to rapidly implement the COLCORONA-NYC Study and allow potentialeligible subjects in the NYC tri-state area to participate. The overall aim of the study is to determine the effectof colchicine on the composite of death or the need for hospitalization in non-hospitalized adults with COVID-19. The data collected through the COLCORONA-NYC study will provide novel data on treatment of COVID-19patients, and have public health implications beyond the scope of the current application, including thepotential reduction in the healthcare resources heavily used in COVID-19 (e.g., hospital beds, ventilators), andpotential future use in other infectious causes of acute respiratory distress syndrome.",2020,2021,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,836425,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00901,3R21AI143454-02S1,Convalescent plasma therapy for COVID-19,"As of April 2nd, 2020, the total number of confirmed COVID-19 cases in the United States exceeds 200,000 andis escalating rapidly. The Institute for Health Metrics and Evaluation projects that COVID-19 cases in the US willsurge mid-to-late April, leading to hospitalization of as many as 2.4 to 21 million people; numbers that willoverwhelm the US healthcare system. Confronted with a pandemic that threatens the lives of millions, with novaccines or effective drugs in sight, the clinical community is evaluating convalescent plasma/serum as an urgentcountermeasure to thwart new infections and ameliorate COVID-19 related morbidity and mortality.The number of recovered individuals in the US is at present 8,500 and as these numbers continue to grow, sowill the availability of plasma rich in SARS antibodies from recovered donors. Infusion of convalescent plasmaprophylactically could immunize health care workers against nascent infections and therapeutic infusion coulddecrease the likelihood of severe disease in infected patients. As a result, several academic medical centersacross the nation have begun trials to use convalescentplasma to treat patients, with many hospitals in NewYork starting treatments this week.Given the potential for broad implementation of convalescent plasma therapy in the US in the coming weeksthere is an urgent need to evaluate the prophylactic and therapeutic ability of convalescent plasma as a stand-alone treatment against COVID-19 using an animal model where timing and dose of infection can be controlled;immunopathology to organ systems can be rigorously assessed by collection of tissue biopsies, and where re-challenge experiments can critically evaluate long-term impact of convalescent plasma therapy on protectiveimmunity.The goals of this study are to determine if human plasma from convalescent COVID 19 patients preventsprimary infection, decreases viremia in the event of breakthrough infections, and alters susceptibility toa secondary challenge. We are collaborating with UCD Health clinicians who are conducting human trial titled:Convalescent Plasma to Stem Coronavirus. We will use an aliquot of the same plasma used in human trials forour rhesus studies. We will inoculate rhesus monkeys with the Davis SARS-CoV-2 isolate (2019-nCoV/USA-CA9/2020; GenBank: MT118835.1) to address these questions within a timeline of 30 days.Urgency and relevance to Emergency Guide Notice: Our animal studies will critically inform efficacy in theshort term and potential risks in the long term of convalescent plasma therapy within 30 days. These criticalanswers can only be rigorously obtained in the setting of controlled animal experiments, and therefore thesestudies are highly urgent as convalescent plasma use becomes a widespread medical countermeasure againstCOVID-19 in the coming weeks. The proposed studies will lay the groundwork for evaluating the ""window ofopportunity"" during which time plasma therapy would be effective post-infection so that plasma infusion maybe maximized for clinical benefit as these animal studies will provide answers within a month.",2020,2020,UNIVERSITY OF CALIFORNIA AT DAVIS,190948,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C00902,3R21AI144374-02S1,Novel long noncoding RNAs in the airway mucous response,"Airway epithelial cells or AECs orchestrate the pulmonary immune responses to airborne viral infections anddrive the successful resolution of infection. Among the immediate early responders that set the tone for innateimmune response, we have identified that as early as half-an-hour of insult, the long noncoding RNA species(lncRNAs) are deployed by the AECs to modulate the epithelial inflammatory response. Specifically, in AECs,we identified a few novel lncRNAs that modulate the expression of inflammatory factors and of ligand/receptorsthat help recruit immune cells. As with the other acute viral infections, a balanced early epithelial responseprovides timely recruitment of appropriate immune cells to thwart the infection and resolve the lung tissueremodeling. However, hosts with hyperreactive or compromised lung mucosal immunity, suffer from higher lungtissue damage, impaired lung functions and overall poor health outcome, as noted in several cases of COVID-19 patients. Overarching goal is to identify and characterize the early host immunomodulatory factors that mightpredispose to severe hyperinflammatory state to novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 disease. The studies proposed will provide novel insight into theimmediate early susceptibility factors of upper airway epithelial cells to SARS-CoV-2 that contribute to adysregulated inflammatory response. Specifically, the archived biological samples from COVID-19 patients willbe analyzed to establish the association of expression levels of the novel lncRNA and SARS-CoV-2 receptors(ACE2 and TMPRSS2) among individuals with various degree of COVID-19 disease severity. The fixed cytospinsand cell pellets will be analyzed for host cellular (lncRNA and receptors) and viral (Spike protein) factors; andwill be validated by qPCR analysis. We will confirm the role of lncRNA by molecular gene editing in AECs culturedin-vitro and treated with a pseudovirions expressing SARS-CoV-2 S protein and validated in separate studiesusing SARS-CoV-2 clinical isolate for infection. Levels of inflammatory factors will be analyzed by multianalyteassays. This proof of concept study will help establish the association of novel lncRNAs with COVID-19pathophysiology that could serve as early biological indicators (biomarkers) of airway immune dysregulation andother comorbidities. Molecular studies will also help determine whether targeting the novel lncRNA can helpreduce or suppress SARS-CoV-2 mediated airway inflammatory responses.",2020,2021,FLORIDA INTERNATIONAL UNIVERSITY,195353,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00903,3R21AI146464-01A1S1,Administrative Supplement to R21: Mechanism and in vivo activity of novel glycan-based therapy against flavivirus endothelial permeability and vascular leak,"Supplement to R21: Mechanism and in vivo activity of novel glycan-based therapy against flavivirusendothelial permeability and vascular leakEvaluation of therapeutics targeting SARS-CoV-2 infection and defining pathogenic mechanisms ofSARS-CoV-2-triggered pulmonary dysfunctionAbstractThe emerging severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2), the causative agent ofcoronavirus disease 2019 (COVID-19), is spreading rapidly across the world, already affecting 199 countries,and predicted to infect up to 60% of the population, with a ~4.4% case fatality rate to date. Novel therapeuticsare desperately needed, and as we are currently investigating anti-flavivirus properties of cyclodextrincompounds (CDs), which have broad antiviral activity, we propose here to expand this investigation to test thesecompounds for anti-SARS-CoV-2 activity in human bronchial epithelial cells (Aim 1). First, we will fast-track theFDA-approved CDs in our collection, and then screen the rest. OSC Dr. Ralph Baric (UNC) will confirm our mostpromising candidates in primary human cells and collaborate on setting up further studies to test them in hismouse models. Based on previous literature and data acquired through the parent grant, we hypothesize thatthese compounds may have direct virucidal activity by inactivating virions, as well as potentially inhibiting cellattachment by blocking the SARS-CoV-2 spike glycoprotein (S) from interacting with glycans and/or the viralreceptor angiotensin converting enzyme 2 (ACE2) on the cell surface. Though infected patients succumb toacute respiratory distress syndrome (ARDS) involving vascular leak, the viral triggers of this pathology areunclear. Experiments with SARS-CoV-1 found that internalization of ACE2 along with virus particles uponinfection reduces ACE2 levels on the cell surface, resulting in increased angiotensin II activity. The angiotensinII activity is believed to result in upregulation of vasoactive molecules such as vascular endothelial growth factorF (VEGF) and disruption of intercellular junctions, both inducing vascular leak. In Aim 2, our optimized systemfor the study of endothelial cell dysfunction, resulting from many years of work with flaviviruses and included inthe parent grant, will be applied to investigate SARS-CoV-2 vascular pathology induced by the viral S proteinand secondary mediators like VEGF. As we have already observed in vitro anti-leak as well as antiviral propertiesfor some of the tested CDs, we also propose to test these candidates as therapeutics to treat COVID-19 diseasemanifestations. As such, this supplemental grant proposal has the potential to define triggers of SARS-CoV-2 S-mediated vascular leak, contributing to ARDS, as well as testing CDs as therapeutics targeting viral infectiondirectly and indirectly via downstream pathogenesis. FDA-approved CDs and derivatives that prove to beeffective as COVID-19 treatments have the potential to be rapidly developed for potential use in patients.1",2020,2022,UNIVERSITY OF CALIFORNIA-BERKELEY,836425,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C00904,3R21AI147017-01S1,Blocking pyroptosis to prevent acute lung injury in SARS-CoV-2 infection,"Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce 2019coronavirus disease (COVID-19), which progresses to acute respiratory distress syndrome and death in asignificant proportion of patients. As outlined in the Notice of Special Interest NOT-AI-20-030, there is a criticallack of understanding of many fundamentals of COVID-19. It is urgent that we determine the mechanism ofacute lung injury caused by SARS-CoV-2 infection and how this might be prevented therapeutically. Many linesof investigation suggest that acute respiratory distress syndrome experienced in severe COVID-19 is due to anoverwhelming host innate immune response. This provides an opportunity to block the innate responsetherapeutically and offset severe disease. Lethal COVID-19 is associated with marked lung inflammation andalveolar disruption, suggesting that alveolar cells die by pyroptosis, an intensely inflammatory form of celldeath. Pyroptosis is mediated by activated inflammatory caspases and cleaved gasdermin D (GSDMD), andpharmacologic inhibitors of these two essential factors have been developed. Based on these findings, wehypothesize that acute lung injury caused by SARS-CoV-2 infection in humans is mediated by intenseinflammation and pyroptosis, and that inhibitors of inflammatory caspases and GSDMD will block lung damage.Importantly, the PI has federal and university clearance to work with highly pathogenic viruses such as SARS-CoV-2 in the University of Pittsburgh's Regional Biocontainment Laboratory, where he has exclusive use of alaboratory suite. We will use precision-cut human lung slices, which are a powerful tool to study pathogenichuman viruses in the context of the intact, human lung. We are already using this system to evaluate acutelung injury caused by highly pathogenic avian influenza (H5N1), which causes acute respiratory distresssyndrome in humans similar to severe COVID-19. We have recently found that alveolar cells infected withH5N1 influenza die by pyroptosis which is prevented by VX-765 and disulfiram, inhibitors of caspase-1/4 andGSDMD, respectively. Notably, both drugs have been shown to be safe in humans. Disulfiram in particular iswidely used to treat other human conditions and is extremely cheap and readily available. In this proposal, wewill first determine the cellular targets of SARS-CoV-2 infection in human lung, and then determine howalveolar cells die following infection. We will then determine if innate immune inhibitors targeting caspase-1/4and GSDMD prevent alveolar cell damage. If we determine that acute lung injury caused by SARS-CoV-2 isprevented by VX-765 and disulfiram, our study would justify the clinical use of these drugs to prevent severeCOVID-19 in this expanding pandemic, which would be a major public health breakthrough.",2020,2021,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,836425,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00905,3R21AI147057-01S1,Mechanistic understanding and inhibition of Zika NS5 protein,"Mechanistic understanding and inhibition of Zika NS5 and SARS-CoV-2 RdRP proteinsABSTRACT Zika virus (ZIKV) and Coronavirus (CoV) are single-stranded RNA viruses that pose grave threat to publichealth. In the first two decades of the 21st century, the global community has already witnessed one outbreakof Flavivirus, Zika virus (ZIKV), and three zoonotic outbreaks of CoV- severe acute respiratory syndrome(SARS)-associated coronavirus (SARS-CoV) in 2002, the Middle East respiratory syndrome (MERS)-CoV in2012, and the most recent, the novel SARS-CoV-2. These viruses are highly transmissible, greatly impactingthe social, societal and economic dynamics. However, there are currently no approved drugs for either ZIKV orfor zoonotic CoV, raising an urgent need for development of novel therapeutic strategies against ZIKV andCoV infection. This application seeks to develop an antiviral strategy targeting the viral core replicationmachinery, RNA-dependent RNA polymerase (RdRP), non-structural protein 5 (NS5) of ZIKV and non-structural protein 12 (NSP12) of SARS-CoV-2. On one hand, the currently identified small molecule inhibitorswill be evaluated for their efficiency on ZIKV or SARS-CoV-2 inhibition. On the other hand, mechanistic detailsof ZIKV NS5 and SARS-CoV-2 RdRP-mediated RNA replication will be investigated, thereby providing a basisfor development of synergistic inhibition strategies targeting various enzymatic steps of ZIKV NS5 and SARS-CoV-2. In Aim 1, structural, biochemical and cellular approaches will be taken to evaluate the inhibition of ZIKVNS5- or SARS-CoV-2 RdRP-mediated de novo RNA synthesis by candidate inhibitors. Through evaluation ofthe inhibitory effects of the candidate inhibitors on ZIKV NS5 or SARS-CoV-2 RdRP, this application willaddress whether these compounds can serve as inhibitors to ZIKV NS5 or SARS-CoV-2, and more importantly,to provide a basis for structure-based drug optimization for ZIKV NS5 or SARS-CoV-2. In Aim 2, themechanistic basis of ZIKV NS5 and SARS-CoV-2 RdRP-mediated RNA replication will be determined throughstructure elucidation of the replication complexes of ZIKV NS5 or SARS-CoV-2 RdRP, combined withenzymatic analyses. The structural knowledge on the replication complexes of ZIKV NS5 and SARS-CoV-2RdRP will then provide a framework for structure-based drug design for comprehensive inhibition of ZIKV NS5and SARS-CoV-2 infection. Together, the proposed studies will provide key mechanistic insights into the viralRdRP-mediated genome replication and establish a foundation for development of effective inhibitors againstZIKV and SARS-CoV-2.",2020,2021,UNIVERSITY OF CALIFORNIA-RIVERSIDE,836425,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Prophylactic use of treatments",2020 +C00906,3R24AI120942-05S1,World Reference Center for Emerging Viruses and Arboviruses (WRCEVA),"New and emerging viruses and arboviruses represent increasing threats to human health, yet theirmechanisms of emergence remain poorly understood, and effective interventions are not available for most.Research on their ecology, evolution, epidemiology, emergence mechanisms, diagnostics, and development ofvaccines and therapeutics remain critical public health needs. The World Reference Center for EmergingViruses and Arboviruses (WRCEVA) comprises a comprehensive, diverse collection of over 6,700 virus strainsin 21 families, as well as antisera, antigens and other reagents to enable research worldwide. Approximately400 new virus strains are added each year, and 1000 viruses and reagents are shipped annually. TheWRCEVA also maintains broad expertise in both novel and traditional approaches to virus identification andcharacterization, and assists with outbreak diagnosis. This proposal seeks to continue these WRCEVAactivities in support of NIH-funded and other research on emerging viruses worldwide through 5 Specific Aims:1. Maintain a comprehensive set of emerging viruses, arboviruses and associated reagents to support research and surveillance. The virus collection as well as antigens, antibodies and other reagents will be continually enhanced to capitalize on new technology, and cDNA clones of selected strains will be added. NextGen sequencing-based quality control practices will be implemented to ensure strain accuracy/purity.2. Discover, isolate and characterize newly acquired viruses by using electron microscopy, next generation sequencing, and serologic methods to determine relationships and taxonomic assignments, and to assess in vitro and in vivo host range. Clinical and field samples as well as viral isolates will be received for identification and characterization, and added to the repository. Critical phenotypes of newly discovered viruses and strains will be assessed by using in vitro and in vivo infections.3. Perform sequencing and phylogenetic analyses of selected virus groups to determine evolutionary histories and emergence mechanisms, patterns of spread and infection, and to rapidly determine the sources of new outbreaks. Key virus strains will undergo genomic sequencing to generate databases that can be exploited for the rapid determination of new outbreak sources, including potential bioterrorism.4. Characterize recently discovered mosquito-specific viruses (MSVs) and determine their evolutionary history, impact on the transmission of arboviruses, and genetic determinants of host range. Selected arbovirus taxa that include mosquito-specific viruses will be studied to understand the genetic basis of their host range restriction and assess their potential as tools to interfere with arbovirus transmission.5. Train scientists in the identification and characterization of emerging viruses and arboviruses. To further enhance research efforts in the U.S. and worldwide as well as to leverage collaborations that feed our collections, basic training in virus identification and characterization will be provided to qualified scientists.",2020,2021,The University of Texas Medical Branch at Galveston,355500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Vector biology",2020 +C00907,3R25GM129222-04S1,PBS NewsHour Health Literacy and Student Reporting Labs: Broad expansion of journalism to increase bioscience literacy in America and support the next generation of biomedical science communicators,"PBS NewsHour Student Reporting Labs will produce a series of high school student journalist virtual interviews with researchers working to understand and fight the COVID19 pandemic. These interviews will highlight the role of student journalism in improving the health STEM literacy of teenagers and the public; connecting students to biomedical and clinical research career pathways and spotlighting the role of health research in education, policy decisions, and civic life. Videos will be edited by Student Reporting Labs youth media producers and published on social media and digital public media platforms to broad audiences of teenagers and adults.",2020,2021,WETA TV 26,11205,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Communication | Policy research and interventions,2016 +C00908,3R34DA050255-01S2,5/7: Longitudinal evaluation of the impact of the COVID-19 pandemic on high-risk new and expectant mothers,"The COVID-19 pandemic represents the most significant environmental event in living history and is leading tounprecedented social, economic and health consequences. There is an urgent need to longitudinally study theimpact of the pandemic on pregnant women and the care they receive, and to understand the consequences fortheir children's birth outcomes and neurobehavioral development. Importantly, women with pre-existingsubstance use, mental health conditions and limited economic resources may be at increased risk for the wide-ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps bybuilding upon ongoing harmonized research efforts across seven geographically-representative sites from theNIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, OregonHealth Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai MedicalCenter, University of Vermont and Northwestern University. We will enroll pregnant and postpartum women intoa multi-wave study in which we assess medical, economic, psychosocial and substance use risk acrosspregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral developmentduring the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 relatedstress leads to differences in birth outcomes, parenting stress and infant temperament and neurodevelopmentand 2) substance use, mental health and economic risk enhance susceptibility to negative COVID-19 relatedhealth and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth and postpartumdata will be obtained across a 3-month period in N=100 pregnant and new mothers per site (providing a totalconsortium sample of N=700) to generate individual temporal profiles of COVID-19 related experiences andresponses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic.Further, to identify avenues for intervention, will evaluate substance use, poor mental health and low socialeconomic status as risk factors and coping, agency and utilization of resources as resilience factors that influenceCOVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects of geographiclocation will be used to examine the influence of pandemic severity, variation in local government policies andresource availability on these outcomes. Finally, we will collect and bank longitudinal perinatal biospecimens inN=40 women per site that will provide a foundation for future studies to evaluate the biological mechanismsthrough which the effects on maternal psychological and physical health influence offspring brain and behavioraldevelopment. Through this analysis of COVID-19 related stress, contextual factors and child outcomes, we willdevelop comprehensive understanding of effects and modifiers of this event on health outcomes in individualsthat vary in dispositional risk during perinatal life, one of the most sensitive timepoints in human development.",2020,2021,CEDARS-SINAI MEDICAL CENTER,170000,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Social impacts,2019 +C00909,3R34DA050272-01S2,3/7: Longitudinal Evaluation of the Impact of the COVID-19 Pandemic on High-Risk New and Expectant Mothers,"The COVID-19 pandemic represents the most significant environmental event in living history and is leading tounprecedented social, economic and health consequences. There is an urgent need to longitudinally study theimpact of the pandemic on pregnant women and the care they receive, and to understand the consequences fortheir children's birth outcomes and neurobehavioral development. Importantly, women with pre-existingsubstance use, mental health conditions, and limited economic resources may be at increased risk for the wide-ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps bybuilding upon ongoing harmonized research efforts across six geographically-representative sites from the NIHHEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, OregonHealth Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai MedicalCenter, University of Vermont, and Northwestern University. We will enroll pregnant and postpartum women intoa multi-wave study in which we assess medical, economic, psychosocial, and substance use risk acrosspregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral developmentduring the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 relatedstress leads to differences in birth outcomes, parenting stress, and infant temperament and neurodevelopmentand 2) substance use, mental health, and economic risk enhance susceptibility to negative COVID-19 relatedhealth and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth, and postpartumdata will be obtained across a 3-month period in N=100 pregnant and new mothers per site (providing a totalconsortium sample of N=700) to generate individual temporal profiles of COVID-19 related experiences andresponses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic.Further, to identify avenues for intervention, will evaluate substance use, poor mental health, and low socialeconomic status as risk factors and coping, agency and utilization of resources as resilience factors that influenceCOVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects of geographiclocation will be used to examine the influence of pandemic severity, variation in local government policies, andresource availability on these outcomes. Finally, we will collect and bank longitudinal perinatal biospecimens inN=40 women per site that will provide a foundation for future studies to evaluate the biological mechanismsthrough which the effects on maternal psychological and physical health influence offspring brain and behavioraldevelopment. Through this analysis of COVID-19 related stress, contextual factors, and child outcomes, we willdevelop comprehensive understanding of effects and modifiers of this event on health outcomes in individualsthat vary in dispositional risk during perinatal life, one of the most sensitive timepoints in human development.",2020,2021,WASHINGTON UNIVERSITY,157761,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Drug users | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Other secondary impacts,2019 +C00910,3R34DA050283-01S2,6/7: Longitudinal evaluation of the impact of the COVID-19 pandemic on high-risk new and expectant mothers,"The COVID-19 pandemic represents the most significant environmental event in living history and is leading tounprecedented social, economic and health consequences. There is an urgent need to longitudinally study theimpact of the pandemic on pregnant women and the care they receive, and to understand the consequences fortheir children's birth outcomes and neurobehavioral development. Importantly, women with pre-existingsubstance use, mental health conditions and limited economic resources may be at increased risk for the wide-ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps bybuilding upon ongoing harmonized research efforts across seven geographically-representative sites from theNIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, OregonHealth Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai MedicalCenter, University of Vermont and Northwestern University. We will enroll pregnant and postpartum women intoa multi-wave study in which we assess medical, economic, psychosocial and substance use risk acrosspregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral developmentduring the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 relatedstress leads to differences in birth outcomes, parenting stress and infant temperament and neurodevelopmentand 2) substance use, mental health and economic risk enhance susceptibility to negative COVID-19 relatedhealth and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth and postpartumdata will be obtained across a 3-month period in N=100 pregnant and new mothers per site (providing a totalconsortium sample of N=700) to generate individual temporal profiles of COVID-19 related experiences andresponses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic.Further, to identify avenues for intervention, will evaluate substance use, poor mental health and lowsocioeconomic status as risk factors and coping, agency and utilization of resources as resilience factors thatinfluence COVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects ofgeographic location will be used to examine the influence of pandemic severity, variation in local governmentpolicies and resource availability on these outcomes. Finally, we will collect and bank longitudinal perinatalbiospecimens in N=40 women per site that will provide a foundation for future studies to evaluate the biologicalmechanisms through which the effects on maternal psychological and physical health influence offspring brainand behavioral development. Through this analysis of COVID-19 related stress, contextual factors and childoutcomes, we will develop a comprehensive understanding of effects and modifiers of this event on healthoutcomes in individuals that vary in dispositional risk during perinatal life, one of the most sensitive timepoints inhuman development.",2020,2021,UNIVERSITY OF VERMONT & ST AGRIC COLLEGE,152961,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Social impacts,2019 +C00911,3R34DA050287-01S2,/7: Longitudinal evaluation of the impact of the COVID-19 pandemic on high-risk new and expectant mothers,"The COVID-19 pandemic represents the most significant environmental event in living history and is leading tounprecedented social, economic and health consequences. There is an urgent need to longitudinally study theimpact of the pandemic on pregnant women and the care they receive, and to understand the consequences fortheir children's birth outcomes and neurobehavioral development. Importantly, women with pre -existingsubstance use, mental health conditions and limited economic resources may be at increased risk for the wide-ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps bybuilding upon ongoing harmonized research efforts across seven geographically-representative sites from theNIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, OregonHealth Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai MedicalCenter, University of Vermont and Northwestern University. We will enroll pregnant and postpartum women intoa multi-wave study in which we assess medical, economic, psychosocial and substance use risk acrosspregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral developmentduring the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 relatedstress leads to differences in birth outcomes, parenting stress and infant temperament and neurodevelopmentand 2) substance use, mental health and economic risk enhance susceptibility to negative COVID-19 relatedhealth and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth and postpartumdata will be obtained across a 3-month period in N=100 pregnant and new mothers per site (providing a totalconsortium sample of N=700) to generate individual temporal profiles of COVID-19 related experiences andresponses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic.Further, to identify avenues for intervention, will evaluate substance use, poor mental health and low socialeconomic status as risk factors and coping, agency and utilization of resources as resilience factors that influenceCOVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects of geographiclocation will be used to examine the influence of pandemic severity, variation in local government policies andresource availability on these outcomes. Finally, we will collect and bank longitudinal perinatal biospecimens inN=40 women per site that will provide a foundation for future studies to evaluate the biological mechanismsthrough which the effects on maternal psychological and physical health influence offspring brain and behavioraldevelopment. Through this analysis of COVID-19 related stress, contextual factors and child outcomes, we willdevelop comprehensive understanding of effects and modifiers of this event on health outcomes in individualsthat vary in dispositional risk during perinatal life, one of the most sensitive timepoints in human development.",2020,2021,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,186462,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Social impacts,2019 +C00912,3R34DA050290-01S2,4/7: Longitudinal Evaluation of the Impact of the COVID-19 Pandemic on High-risk New and Expectant Mothers,"While the rate of neonatal abstinence syndrome has reached a staggering 6.5 per 1,000 births nationwide, theshort- and long-term effects of in-utero opioid exposure are far from clear. We lack fundamental knowledge ofneurotypical neonatal development and struggle to disentangle the effect of opioid exposure from otherprotective and risk factors impacting infant health. The fetal stage of brain development is a critical periodwhen foundational aspects of brain structure and function are being established. In addition, postnatal braindevelopment and specialization are shaped by environmental experiences thus allowing maturation to beinfluenced by lifestyle factors associated with opioid use. This Phase I project will plan for a large scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotionaldevelopment beginning prenatally through childhood. The University of Pittsburgh is one of four linked sitesincluding Oregon Health and Sciences University, New York University and the University of Vermont that willaddress key challenges critical to the success of the planned Phase II study. Aim 1 will develop, implementand evaluate innovative recruitment and retention strategies for high-risk populations through a longitudinalsurvey of 150 pregnant women per site (n=600 across sites), half of whom are opioid using. Aim 2 willimplement a multi-site, standardized, longitudinal research protocol by enrolling 20 pregnant women per site(n=80 across sites), half of whom are opioid using. This prospective longitudinal study will collect fetal andneonatal multimodal MRI, biospecimens, and maternal psychosocial and health assessments. Aim 3 willevaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, andintegration across sites. We will test the efficacy of (A) real-time motion monitoring/quality assessment forimproving overall data quality and (B) time-savings versus MRI quality using new acceleration sequenceprotocols. This approach will inform and set a strong foundation for a comprehensive and effective Phase IIresearch plan. The University of Pittsburgh site is led by a highly productive, NIH-funded investigative teamwith multidisciplinary expertise in substance use (Krans, Bogen), pregnancy (Krans), and fetal, neonatal, andpediatric neuroimaging (Luna, Panigrahy). Specifically, our team has established study protocols that yieldexcellent recruitment (~76%) and retention (~74%) rates among opioid using pregnant women, has substantialexperience with imaging the immature brain (fetal/neonatal) and is a leader in developmental cognitiveneuroscience using multimodal imaging to investigate neural mechanisms underlying neurocognitivedevelopment through adolescence. We will leverage our on-going, NIH-funded, multi-center neuroimagingstudies to provide imaging harmonization techniques and assist with the development of structural fetal brainand placental imaging pipeline for all linked sites to assistant with development of Phase II protocol. Further,we will pilot innovative studies of age-related Iron deposition and quantitative fetal MR spectroscopy.",2020,2021,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,158349,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts,2019 +C00913,3R34DA050291-01S2,2/7: Longitudinal evaluation of the impact of the COVID-19 pandemic on high-risk new and expectant mothers,"The COVID-19 pandemic represents the most significant environmental event in living history and is leading tounprecedented social, economic and health consequences. There is an urgent need to longitudinally study theimpact of the pandemic on pregnant women and the care they receive, and to understand the consequencesfor their children's birth outcomes and neurobehavioral development. Importantly, women with pre-existingsubstance use, mental health conditions and limited economic resources may be at increased risk for the wide-ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps bybuilding upon ongoing harmonized research efforts across seven geographically-representative sites from theNIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University,Oregon Health Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars SinaiMedical Center, University of Vermont and Northwestern University. We will enroll pregnant and postpartumwomen into a multi-wave study in which we assess medical, economic, psychosocial and substance use riskacross pregnancy and the perinatal period, studying associations of these factors to infant neurobehavioraldevelopment during the first year of life. Our central hypotheses include: 1) individual variation in perinatalCOVID-19 related stress leads to differences in birth outcomes, parenting stress and infant temperament andneurodevelopment and 2) substance use, mental health and economic risk enhance susceptibility to negativeCOVID-19 related health and psychosocial outcomes. To pursue these aims, prospective longitudinal survey,birth and postpartum data will be obtained across a 3-month period in N=100 pregnant and new mothers persite (providing a total consortium sample of N=700) to generate individual temporal profiles of COVID-19related experiences and responses, comparing outcomes with existing data from maternal-infant cohortsobtained prior to the pandemic. Further, to identify avenues for intervention, will evaluate substance use, poormental health and low social economic status as risk factors and coping, agency and utilization of resources asresilience factors that influence COVID-19 related maternal stress and child health and neurobehavioraloutcomes. The effects of geographic location will be used to examine the influence of pandemic severity,variation in local government policies and resource availability on these outcomes. Finally, we will collect andbank longitudinal perinatal biospecimens in N=40 women per site that will provide a foundation for futurestudies to evaluate the biological mechanisms through which the effects on maternal psychological andphysical health influence offspring brain and behavioral development. Through this analysis of COVID-19related stress, contextual factors and child outcomes, we will develop comprehensive understanding of effectsand modifiers of this event on health outcomes in individuals that vary in dispositional risk during perinatal life,one of the most sensitive timepoints in human development.",2020,2021,OREGON HEALTH & SCIENCE UNIVERSITY,180332,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity,2019 +C00914,3R34DA050343-01S2,Understanding the effects of COVID-19 on maternal substance use,"The pandemic resulting from the emergence of novel severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) prompted governmental orders across the U.S. to restrict socialinteraction to reduce the spread of the virus. Reduced social contact may have adverse effectson individuals in recovery from substance use and abuse. Moreover, substance use is known toincrease following natural disasters.1,2,3 This study will explore experiences related to thecoronavirus disease (COVID-19) pandemic that are of particular importance for the PlanningPhase (Phase I) of the HEALthy Brain and Child Development (HBCD) study. Moreover, thisstudy will inform the large-scale, multi-site research study (Phase II), as crises such as naturaldisasters are likely to occur and affect sites during the longitudinal study. Our five-site Phase Iconsortium, included qualitative interviews and focus groups to inform data collection practicesfor the Phase II study using rigorous methods. Additional data collection will allow the team tobetter understand the needs of this unique population of women with substance use disorders(SUD) in response to the health, economic, and psychosocial demands of the pandemic. Thisstudy will improve recruitment and retention of subjects in the midst of other natural disasterswhich may adversely affect retention across the longitudinal study.",2020,2021,OSU CENTER FOR HEALTH SCIENCES,145460,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Other secondary impacts,2019 +C00915,3R35GM119582-04S1,Statistical methods for real-time forecasts of infectious disease: expanding dynamic time-series and machine learning approaches for pandemic scenarios,"The emergence and global expansion of SARS-CoV-2 as a human pathogen over the last four monthsrepresents a nearly unprecedented challenge for the infectious disease modelling community. This pandemichas benefitted from huge volumes of data being generated, but the rate of dissemination of these data hasoften outpaced existing data pipelines. While the last decade has seen significant advances in real-timeinfectious disease forecasting - spurred by rapid growth in data and computational methods - thesemethods have primarily focused on seasonal endemic diseases based, are based on historical data, and sodo not apply easily to this novel pathogen, or to pandemic scenarios. New methods are needed to leveragethe wealth of surveillance data at fine spatial granularity, together with associated information about policyinterventions and environmental conditions over space and time, to reason directly about the mechanisms toforecast and understand the transmission dynamics of SARS-CoV-2 transmission. These methods must usesound statistical and epidemiological principles and be flexible and computationally efficient to provide real-time forecasts to guide public health decision-making and respond to changing aspects of this global crisis.The central research activities of this project are (1) to develop scalable, computationally efficient Bayesianhierarchical compartmental models to flexibly respond to state-level public health forecasting needs, and (2)to design models and conduct analyses to draw robust inference about the effectiveness of interventions inimpacting the reproductive rate of SARS-CoV-2 infections within the US to build an evidence-base forcontinued responses to COVID-19 and future pandemics.",2020,2021,UNIVERSITY OF MASSACHUSETTS AMHERST,78507,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2016 +C00916,3R35GM127064-03S1,Discovery of pseudoknots in the SARS-CoVID-2 RNA genome with SNP analysis,"The Bevilacqua lab has contributed to the field of RNA biology through two disparate approaches. One isrigorous ribozyme mechanism and the other is discovery-based RNA structural genomics. A major goal of theparent award is to bridge these two areas to discover new RNA biology and to characterize it at the molecularlevel. This proposal advances ways to investigate RNA structure and its contribution to the COVID-19outbreak. We have already computationally identified structural domains in the RNA genome of SARS-CoV-2,which causes COVID-19, and confirmed these with recent reports on BioRxiv. Uniquely, we identified potentialpseudoknots, which are regions of RNA folding complexity that are typically essential for function. The plan forthe summer is for our undergraduate student Peter Forstmeier to work through the thousands of availableSARS-CoV-2 genomes that contain single nucleotide polymorphisms (SNPs) to identify changes in pseudoknotstrength and RNA folding. SNPs in pseudoknots may lead to changes in the stability of the structure, as so-called riboSNitches. The effect of these SNPs on pseudoknots may have implications on the spread andpotential virulence of COVID-19. Our hypothesis is that such information will provide targets for therapeutics,both antisense oligonucleotides and small molecules, which can halt spread of the virus. This administrativesupplement would provide a unique opportunity for Peter to advance his training to pursue his eventual goal ofbeing a physician-scientist. Because it is computational, it is amenable to working from home during thepandemic, and we can mentor Peter using videoconferencing. Peter is a rising junior and has already spent ayear in the Bevilacqua lab developing his coding skills and preparing a pipeline to search for novel RNAstructures making him a good fit for this project.",2020,2023,PENNSYLVANIA STATE UNIVERSITY-UNIV PARK,7605,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2018 +C00917,3R37AI080289-11S1,Demystifying the antiviral activity of the IgG3+ antibody response,"Since 2002, several coronaviruses have emerged able to cause severe respiratory disease, however no vaccineis available to prevent these rapidly spreading pathogens. Vaccine design has specifically lagged due to our lackof understanding of the correlates of immunity against these pathogens. Both cellular and humoral immuneresponses have been implicated in resolution of disease, but to date only the passive transfer of antibodies hasbeen shown to confer complete protection in mice. Interestingly, the transfer of both ""neutralizing"" and non-neutralizing antibodies have shown protective efficacy, highlighting the role of multiple humoral mechanisms inlimiting viral infection/spread. The precise mechanism of action of these antibodies that have the most profoundimpact on limiting disease is currently unclear, but if elucidated could provide critical insights for the developmentof effective vaccines against COVID-19 and other coronaviruses. Thus, here we aim to take a systematicapproach to dissect and define both the polyclonal and monoclonal mechanisms by which antibodies conferprotection against COVID-19. Specifically, samples from DNA- and adenovirus 26 (Ad26)- COVID-19 Spikeprotein (S) immunized animals, that will be challenged with COVID-19, will be comprehensively profiled usingSystems Serology, to define the functional humoral immune responses linked to protection from infection/diseasein mice, ferrets, and macaques. Machine learning modeling will be employed to discern key immune responsefeatures that translate usefully across these diverse animal contexts. Coupled to a novel systems-Fc-engineeringapproach, the COVID-19 CR3022 monoclonal antibody will be engineered to specifically define the Fc-effectorfunctions that provide the greatest impact on limiting disease. Collectively, these studies will not only definecorrelates of immunity across vaccines and species, but also provide mechanistic insights into the precisemechanisms by which antibodies may confer protection in the context of future vaccines.",2020,2022,MASSACHUSETTS GENERAL HOSPITAL,391727,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00918,3R42AG059451-02S1,"Novel Arm Restraint For Critically Ill Patients To Reduce Immobility, Sedation, Agitation and Cognitive Impairment","The goal of this Administrative Supplement to Parent Grant R42AG059451 in response to responsive to PAS-17-065 is to allow mass production of a novel device to provide relief to critically ill patients affected by thesedation shortage resultant from the COVID-19 pandemic. Through access to plastic injection molding,assembly and logistics, Healthy Design will be able to realize an acceptable time frame to produce, makeavailable and support the use of its novel medical device. Healthy Design expects that streamlining productionwill minimize sedation usage while minimizing restraint, agitation, and delirium and increasing mobility withoutextra staff or other valuable resources.The COVID-19 pandemic has caused a ripple effect in our ICU supply chain, not the least of which is asedation shortage. We are conserving as much as possible by utilizing the less expensive and more abundantmedications from the benzodiazepine sedative category which were until now discouraged by published ICUguidelines; however, these supplies are also rapidly depleting. In the ICU setting, sedation is required forconfused patients with vital medical equipment, restrained intubated patients, patients with severe acute lungdisease resulting in ventilator dyssynchrony, and for those dyssynchronous patients who require a paralytic.While all of these categories of illness include COVID and non-COVID patients, in order to reserve sedation forthe most needy patients, we must reduce sedation for other patients. The Exersides™ Refraint™ was createdto safely reduce the need for sedation by reducing restraint and agitation. As immobility, agitation and sedationare known to lead to delirium and post-intensive care syndrome (PICS), there will likely be further benefits ofthe device. Thus far, Exersides™ has successfully completed a preliminary Pilot Study, a Phase I trial and,except for the COVID-related trial suspension, is currently in its multi-site Phase II trial as part of this STTRFast-Track award.Another phenomenon we are facing due to the current pandemic is an almost complete absence of familyvisitation. Together with an overstretched ICU staff, this loss is leading to patients spending more time alonewhile critically ill. Lack of availability to attend to each patient actually encourages increased sedation andrestraint in an attempt to keep everyone safe while caring for more patients. Exersides™ is intended to keepvital tubes and lines safe while allowing thoracic movement for pulmonary secretion clearance, gut functionand muscle tone preservation. Physicians are realizing they will be making difficult choices as to whether it ishumane to place a critically ill patient on a ventilator and strap them to the bed while awake. From our trials todate, we work with nurses and physicians who are familiar with Exersides™ and understand the concept of asafe, alone, awake, mobile intubated patient.The pathway to Healthy Design's ultimate goal of making the Exersides™ Refraint™ available to all hospitalsin time to address the concerns forced upon us by the sedation shortages is clear. Design Controls and aQuality Management System are in place and FDA registration is completed. Design files for translation from3D printing used to make prototypes to injection molding for mass production are in their final stages. HealthyDesign will partner with Progressive Plastics, Egli Machine Co. or Sinicon Plastics, depending on their bidswhich are currently under consideration. Manufacturing Solutions Inc and Kalow Technologies are bidding on acontract to assemble, package and ship the device. Preliminary quotes are listed in the Budget Justificationsection of this application. Vermont Manufacturing Extension Center is providing assistance to Healthy Designto foster its own workforce including receiving, assembly, and distribution. Healthy Design's management teamwill lead the efforts to liaise with hospital administrators and purchasing agents to provide a seamless processfor procurement of the novel device. Clinical educators will be available to provide remote training and supportto sites for onboarding of the Exersides™ Refraint™.",2020,2021,Healthy Design Ltd. Co,374498,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2018 +C00919,3R43EB026363-01S1,"Droplette: A Platform Technology for At-Home, Effective, and Rapid Pulmonary Delivery to Reduce Ventilator Use & Hospitalization","Significance: COVID-19 causes significant lung damage in a subset of patients leading to a cascade ofinflammatory cytokine activation (cytokine storm) that develops into acute respiratory distress syndrome (ARDS).There are several classes of FDA-approved therapeutics that have significant potential in mitigating thepulmonary inflammation when effectively delivered into the lower airways. However, there is a significanttechnology gap in the ability to safely and rapidly dose and administer these drugs to the lungs.Nebulizers are not used for Covid19 patients due to sterility/transmission risks since their use enables viralparticles to linger in the air for hours; they are also not easy to use or sterilize. Inhalers produce mists that donot reach the lower airways. We have developed a patented platform trans-tissue delivery system (Droplette)comprising the unique combination of a piezoelectric transducer and diaphragm pump to physically deliver largetherapeutics into cells and deep through tissue. We hypothesize that this device will allow deep and more rapiddelivery into the lower airways into the lungs of COVID-19 patients relative to standard nebulizers withoutrequiring active inhalation based on the measured droplet sizes (<3 µm) in the mist generated by the device (i.ethis can function as a rapid, low cost, more effective nebulizer for at-home use). Early intervention and at-home administration will reduce the hospitalization burden and need for ventilation- leading to decreasedhospitalization rates, fewer patients who need to be placed on a ventilator and lower mortality. Additionally, thedevice accepts pre-filled sterile one-time use cartridges containing therapeutic formulations and is Bluetooth-enabled with a paired app, allowing a provider to monitor patients' usage via telemedicine. PreliminaryData: Droplette has been tested extensively across ex vivo, in vivo, and pilot human studies. We have previouslydemonstrated that Droplette can deliver naked large (>1 MDa) mRNA to the basal layer of mucosal tissue andhypothesize that the same mechanism can enable pulmonary delivery. The device generates a fine, low-pressure mist in a unique transitional flow regime and produces consistent spray pattern, plume geometry,droplet size distribution, and particle size. Droplette generates 100% fine mist (<4.7 µm) that dispenses~1mL/min with a flow velocity of 1-5 m/s. Specific Aims: We will demonstrate that Droplette can delivertherapeutics into the lungs & lower airways. In Specific Aim 1 we will Assess efficacy and delivery of Droplettepaired with Hypertonic Saline (7%) (HS-7%) in treating ARDS/Cytokine storm using cascade impaction studiesand cell/animal studies using models that will mimic a COVID-19 like cytokine storm. In Specific Aim 2, we willdo the same set of studies using two classes of therapeutics currently in trials for COVID-19: epinephrine & anti-IL-6 antibodies. Collectively, the results from these studies will demonstrate efficacy of our device for pulmonarydelivery in COVID-19 patients to treat cytokine storms & resulting lung damage.",2020,2021,NOVOPYXIS INC,248206,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2020 +C00920,3R44AI109926-05S1,Development of VLP vaccine for RSV,"The SARS-CoV-2 responsible for the Coronavirus disease 2019 (COVID-2019) outbreak represents amajor public health threat that urgently requires development of a small animal model that can be used totest medical countermeasures. This supplement proposal is a logical extension of our parent grant,Development a VLP Vaccine for RSV (PO: Sonnie Kim, R44 AI109926). The laboratory of the PI andhis collaborators specialize in both, developing new vaccines, vaccination strategies, and therapies toovercome viral infection and viral-induce Acute Respiratory Distress Syndrome (ARDS), and into thedevelopment new model of human respiratory viral infectious diseases. The cotton rats is known for theiroutstanding translational value for human health and, in contrast to mice, are highly susceptible to infectionwith non-adapted human viruses, including those that specifically target the respiratory tract. Cotton ratsare also notoriously difficult to work with, and SBI has the utmost experience and capabilities required towork with these animals. We are in a position to offer our decades-long expertise in the cotton rat model todevelop fully a SARS-CoV-2 model of infection that can recapitulate Acute Respiratory Distress Syndrome(ARDS) induced by SARS-CoV-2 and be used for an expedient and reliable testing of experimentaltherapeutic and vaccine candidates. All resources are in place for the rapid start of work, including our in-house colonies of two different species of inbred cotton rats (Sigmodon hispidus and Sigmodon fulviventer),We have established very strong collaboration with Bioqual Inc., a close by company with which we havecollaborated in the past for many projects, including a SBIR phase II. They will provide both, ABSL3 andBSL3 facilities, as well as experienced personnel, and the newly isolated SARS-CoV-2 virus. With thishighly-regarded team of senior scientists recognized for the expertise in developing novel cotton rat modelsand for their expertise in targeting innate immune pathways, we hypothesize that cotton rats willrecapitulate ARDS observed in recent human cases of SARS-CoV-2 infection and become a reliable smallanimal model for screening newly developed vaccines and therapeutics, such as TLR4 antagonists, that willresult in a more rapid medical countermeasure.",2020,2021,SIGMOVIR Biosystems Inc,476975,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C00921,3R44AI122371-04S1,Development of a rapid response nucleic acid vaccine strategy for coronavirusepidemics,"In response to the emerging COVID-19 (SARS-CoV-2) pandemic, this supplement proposal to R44 AI138733-01 will leverage our cutting-edge nucleic acid vaccine strategies, some of which that were developed under thisparent grant. Here, we request supplement funding to develop candidate COVID-19 DNA and RNA vaccinesexpressing optimally designed immunogens for the SARS-CoV-2 spike protein. Nucleic acid (DNA and RNA)vaccines offer significant promise for providing a rapid response solution to emerging infectious diseasesbecause only a partial genetic sequence of the pathogen is needed to generate a new vaccine. Following in vivodelivery, DNA and RNA vaccines lead to in situ production of antigens, negating the need for a complexmanufacturing and process development required for purified recombinant protein, inactivated or live attenuatedvaccines. Nucleic acids can also be manufactured at low cost and are very stable at room temperatureeliminating the need for a cold chain. This provides a significant savings in the time needed to advance a newvaccine from identification of genetic sequence to clinical testing and distribute it to the population. In addition,possibly due to the ability of nucleic acid vaccines to present antigens in their natural conformation in vivo,antibody responses are generally of higher avidity and broader specificity when compared to antibody inducedby subunit protein vaccines. Further, the intracellular expression of antigens also induces robust T cell responsesincluding potent CD8+ T cell responses that can more broadly recognize different viral strains and mediateprotection via enhanced clearance of the infection. Our approach will compare our optimized DNA and RNAvaccine platform technologies alone and in combinations to identify a lead approach that induces the highestand most rapid development of protective levels of neutralizing antibody after a single administration. In addition,since nucleic acid vaccines tested in our lab have been shown to induce antibody and/or T cell responses thatinduce cross-protective immunity in our universal influenza vaccine studies under our parent grant, we willdetermine if the candidate vaccines exhibit cross reactivity against other coronavirus strains for broaderprotection against future coronavirus strains with epidemic or pandemic potential. Our Aims include: Aim 1-Design and compare immunogenicity of candidate SARS-CoV-2 DNA and RNA vaccines. Aim 2 - Maximizeimmunogenicity of nucleic acid vaccines and rapid manufacture by combining DNA and replicon mRNA vaccinestogether or with recombinant protein and optimizing DNA and mRNA formulations. Aim 3 - Safety andimmunogenicity of the lead COVID-19 nucleic acid ± protein vaccine in the preclinical nonhuman primate model.If successful, should identify a lead candidate COVID-19 nucleic acid vaccine for phase I human clinical trials.",2020,2022,Orlance Inc,908934,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C00922,3R61DA047032-03S1,Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics,"SARS-COV-2 and the associated respiratory disease, COVID-19, has been linked to over 100,000 deathsglobally since fall of 2019. Severe COVI9 and associated mortality has strongly been correlated withseveral comorbidities including age, diabetes, immunodeficiencies and cardiovascular diseases. Howbehavioral or lifestyle factors, in particular tobacco use, influence the course of COVID19 has not beendirectly examined. Tobacco use, smoking and vaping, is a particular concern since it is directly linked topoor lung health and increased susceptibility to bacterial and viral pulmonary infections including SARSand MERS coronaviruses. Furthermore, patients that use tobacco products are at higher risk for thecomorbidities such as, diabetes and cardiovascular diseases that are risk factors for COVID19. SARS-COV2 infection and tobacco use both trigger and perpetuate a dysfunctional inflammatory cytokineresponse in the lung. We hypothesize that smoking and vaping are primary risk factors associatedwith severe COVID19 and that they directly contribute to morbidity and mortality by exacerbatingthe uncontrolled pulmonary cytokine storm.We will adapt transcriptomics approaches established for our current R61, ""Effect of Opioid Use Disorderon HIV Latent Reservoirs and Immune Dysfunction Assessed by Single-Cell Transcriptomics"" to gaininsights into COVID19 mechanism of disease. We will initially obtain blood samples from the BostonMedical Center COVID19 biorepository collected from COV19+ smokers and nonsmokers and compare toCOV19-negative individuals and perform state of the art digital drop single cell RNA sequencing, singlecell ATAC-sequencing and computational analysis to provide insights into key innate immune signaturesthat directly contribute to COVID19. Although we will initially focus on blood since this is an easilyobtainable tissue and often provides an immunological footprint of disease, we will compare blood withother clinical tissue samples including lung fluids as they become available.The completion of these studies will provide new insights into COVID19 biomarkers and dysregulation ofspecific inflammatory pathways. A primary goal is to use the results from these proposed experiments togenerate new hypotheses that will guide more mechanistic studies towards understanding epigeneticevents that directly and indirectly influence the course of pulmonary lung infections.",2020,2021,Boston University,164927,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2018 +C00923,3R61DA047034-03S1,Molecular profile of proviral reservoirs in HIV-infected drug users,"The novel SARS-CoV-2 Coronavirus has, within a short time, caused a worldwide pandemic of epic proportions and unprecedented dimensions in modern times. As previously observed in the HIV-1 epidemic, understanding the complex pathogenesis and host response of SARS-CoV-2 infection will represent the cornerstone for developing effective treatment strategies. One particularly important aspect will be to identify subpopulations of patients with increased vulnerability to SARS-CoV-2, and to understand possible connections between SARS-CoV-2 and other viral infections. Moreover, the SARS-CoV-2 pandemic occurs in the midst of the ongoing opioid epidemic in the US, and people who use opioids are likely to have specific behavioral and immunological characteristics that may increase susceptibility to severe SARS-CoV-2 infection. In the proposed work, we will perform what we consider the first dedicated analysis of virological and immunological characteristics of SARS-CoV-2 patients with HIV-1 co-infection, and with opioid abuse. Our work will focus on identifying SARS-CoV-2/HIV-1 co-infected patients with or without opioid abuse, using large cohorts of SARS-CoV-2 patients that are currently actively enrolling in the Boston area (Specific aim 1). Using well pedigreed samples from such patient cohorts available through a centralized biorepository, we will conduct virological and immunological studies to define the replicative behavior of SARS-CoV-2 in such patients and characterize host immune cell perturbations and inflammatory markers, relative to SARS-CoV-2 -monoinefcetd patients (Specific aim 2). Finally, we will determine how SARS-CoV-2 infection affects viral reservoir cells in HIV-1 infected patients, a question of important significance as modeling predicts that a large proportion of all US citizens, and of all US-based HIV-1-patients, may ultimately be exposed and infected with SARS-CoV-2 (Specific aim 3). Together, these proposed studies will address fundamental question of SARS-CoV-2 pathogenesis and critically define the understanding of SARS-CoV-2 pathogenesis in HIV-1 patients.",2020,2021,MASSACHUSETTS GENERAL HOSPITAL,168000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2018 +C00924,3U01AI069918-14S1,NA-ACCORD COVID-19 Supplment,"The North American - AIDS Cohort Collaboration on Research and Design (NA-ACCORD), the Region 1representative of the IeDEA network, aims to describe the HIV epidemic in the US and Canada and answerquestions important to the contemporary care and health of persons with HIV. We propose to leverage theresearch infrastructure of the NA-ACCORD to support our infectious disease epidemiologists and clinical co-investigators as they pivot to answer urgent COVID-19 questions in people with (PWH) and without (PWOH)HIV among existing and new cohorts. By supporting a) 2 existing cohorts and the establishment of 3longitudinal COVID-19 clinical cohorts curated from available electronic health record (EHR data), b) datamanagement and analytic expertise specific to the profound health impacts of infectious disease, c) a library ofCOVID-19 data collection tools, and d) the sharing of EHR-based algorithms for COVID-19, we will acceleratethe answers to the following urgent COVID-19 questions: 1) Who is getting tested for SARS-Cov-2, whatproportion are positive, and what are predictors of a positive test? 2) What are risk factors for hospitalizationafter testing positive for SARS-Cov-2? 3) Do angiotensin-converting enzymes (ACE) inhibitors or angiotensin IItype-I receptor blockers (ARBs) increase the risk of severe COVID-19 illness? 4) What is the impact of thehealthcare system's adaptation to the surge of people becoming ill with COVID-19 on the all-cause mortalityamong those with HIV (a chronic condition that requires routine care)? Infectious disease epidemiologists andclinicians are needed to answer urgent COVID-19 questions. The NA-ACCORD will support co-investigatorsand their analytic teams, provide the infrastructure to share information, and examine the heterogeneity inanswering these COVID-19 questions investigated expeditiously in 5 existing and new cohorts.",2020,2021,JOHNS HOPKINS UNIVERSITY,5429240,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C00925,3U01AI110397-05S1,School Inner-City Asthma Intervention Study : Human Epidemiology and Response to SARS-COV-2 (HEROS) Supplement,"COVID-19, the infectious disease caused by SARS-CoV-2, is rapidly affecting humans around the globe.While initial epidemiological data have focused on cases that resulted in severe respiratory disease seenpredominantly in adults, little information regarding the infection burden in children is available. This iscomplicated by the observation that many virologically-confirmed cases in children are asymptomatic. Homeenvironments are established sources of exposure that exacerbate symptoms of asthma and home-basedinterventions are proven effective. Prior to the inception of the School Inner-City Asthma Study (SICAS-1), noAmerican study had comprehensively evaluated the relationship between urban exposures in school,classroom, and home environments and asthma morbidity. Nearly all elementary school children spend 7 to12 hours a day in school, and most of that time is spent in one classroom. From SICAS-1, we learned thatstudent classroom-specific mouse allergen, mold, and particulate pollutant exposure is associated withworsening symptoms. We also demonstrated our ability to reduce these exposures in a busy, school setting.Our proposal builds upon our established, successful school-based infrastructure to determine whether aschool/classroom intervention will efficiently and effectively improve asthma morbidity by reducing theseexposures. Our goal is to determine the efficacy of school/classroom based environmental intervention inreducing asthma morbidity in urban schoolchildren. Our central hypothesis is that reducing classroom/schoolexposure to mouse allergen, mold, and particulate pollutants will decrease asthma morbidity in students withasthma. We plan to test this hypothesis in an intervention study of 250 elementary students with asthma frommultiple classrooms in 40 Boston inner-city elementary schools. Our clinical trial aims are to determine theeffectiveness of a school/classroom based environmental intervention (school integrated pest managementand classroom air purifying filter units within these schools) to reduce asthma morbidity. The supplement tothe parent grant is to leverage the cohort for the to participate in the multi-center survey entitled HumanEpidemiology and Response to SARS-CoV-2 (HEROS), study. This study can be rapidly implemented andrealistically conducted without necessitating any visits to a clinical research center. In addition to the need forsurveying children for asymptomatic SARS-CoV-2 infection, this study will allow a comparison betweenchildren with asthma and other atopic conditions and children without those conditions through remote surveysand collection of samples. This study is an unprecedented, high impact opportunity to leverage the parent trialwith in scope in understanding how SARS-C0V-2 differentially affects children with the condition of interest,compared to children without it.",2020,2020,BOSTON CHILDREN'S HOSPITAL,211342,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C00926,3U01AI122285-05S1,"Microbial, immune, metabolic perturbations by antibiotics (MIME study)","As SARS-CoV-2 is sweeping through the USA, healthcare workers (HCW) are our first line ofdefense. But they too are susceptible to becoming infected, resulting in physical illness, loss ofproductivity, and potential for disease transmission to patients. Our long-term goal is to protectHCW taking care of SARS-CoV-2-infected patients as well as their families, communities, andthe general population. Our specific objective is to rapidly establish a prospective cohort tocharacterize the factors related to viral transmission and disease severity in a large healthcaresystem in both healthcare settings and workers' households. Our central hypothesis is thatHCW are at higher risk of acquiring and transmitting SARS-CoV-2 and COVID-19 comparedwith non-healthcare workers (NCHW). We propose to address this hypothesis by recruiting andfollowing 500 HCW and 250 age- and sex-matched NHCW within a large academic healthsystem, Rutgers Biomedical and Health Sciences (RBHS). By intensively following participantsover a six-month period and collecting serial biospecimens (nasopharyngeal swabs and blood)and questionnaire data at nine time points, we will be uniquely situated to characterize SARS-CoV-2 transmission and risk factors for COVID-19 among HCW and their families. Our specificaims are: (i), to assess the baseline prevalence of SARS-CoV-2 and COVID-19 in the studypopulation; (ii), to characterize the natural history of SARS-CoV-2 infection in a diverse USworkforce, including the incidence of asymptomatic infections and critical illness; (iii), todetermine the incidence of SARS-CoV-2 and COVID-19 in healthcare workers compared withnon-healthcare workers; (iv), to identify the risk factors for acquiring SARS-CoV-2 anddeveloping COVID-19; (v), to determine the duration and extent of SARS-CoV-2 shedding; and(vi), to determine the rate and direction of transmission of SARS-CoV-2 within households. Ourmultidisciplinary team has the opportunity, population, resources, and motivation to immediatelytackle these crucial questions and to mobilize in the early stages of this public health crisisbefore overwhelming infection occurs in the US. The proposed cohort study will produceimmediate, actionable, and translatable knowledge about protecting the healthcare workforce.The established cohort and repository of ~15,000 biospecimens will also serve as a foundationfor future mechanistic studies. The coordinated activities of our team working within a largehealthcare system will advance efforts to control, treat, and prevent COVID-19, with focus onthe safety of HCW and the staffing of hospitals during this continuing epidemic.",2020,2021,Rutgers The State University of New Jersey,1558030,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2020 +C00927,3U01AI131344-04S1,Development of Mucosal and Systemic Immunity and Risk of Food Allergy,"Transmission of the SARS-CoV-2 virus in human milk (HM) is unknown with only 11poorly-described studies, reporting detectable virus in just 1 of the total 36 breastmilk samples. Further,it is possible that maternal SARS-CoV-2 infection during pregnancy and lactation confers some specificprotection through antibodies. Only one study reports the presence of IgG to SARS-CoV-2in HM. Alarming examples of antibody-dependent enhancement of other viral infections illustrate howcritical it is to understand both the profile and activity of these antibodies in HM. It is critical then tounderstand the transmission risks and protective factors between mother and child throughbreastfeeding.Design: We propose a longitudinal cohort study of COVID-19+ mothers to determine risks oftransmission (viral exposure of infants through breastfeeding by presence in HM and on areolar skin)and protective factors (SARS-CoV-2-specific antibody response in HM, profile and neutralizationcapacity) of breastfeeding. Longitudinal samples will allow us to assess temporal changes over diseasecourse.Methods: We will enroll 50 COVID+ mothers in the first 3 months of lactation, 25 symptomatic and 25asymptomatic. We will concurrently collect samples from two locations: The University of RochesterSchool of Medicine and Dentistry and New York University, NY. These sites will provide robust andstaggered access to patients. We will recruit through local hospitals and social media platforms. Motherswill provide informed eConsent. IRB approval has been received. All samples will be self-collected inthe hospital (if admitted) or in the home. There will be no physical contact between study staffand participants. Mothers will express and collect whole breastmilk on Days 0 (enrollment), 3, 10, 19,28, and 90, breast skin swabs on Days 0 and 3 and whole blood by fingerstick on days 0 and 90. Theywill also be instructed to provide a frozen HM sample from Day -7, if available.Analysis: RNA will be extracted from HM and breast skin swabs in the Jarvinen-Seppo lab. SARS-CoV-2 genomic RNA will be quantitated using RT-qPCR three amplicon probe-based systemas recommended by CDC. We will compare presence and changes in SARS-CoV-2 in HM via repeatedmeasures analysis. We will assess SARS-CoV-2 and other coronavirus antibodies in maternal fingerprick and HM to S and N proteins of SARS1, SARS2, HKU1, 229E, NL63 and OC43 by Luminex onthe mPLEX-CoV system developed and validated by the Zand lab. Repeated measures analysis will beused to compare the changes in concentration of HM anti-SARS-CoV-2 antibodies over the time-courseof disease progression and also between women with mild to severe symptoms.Impact: These results are critical to understand the risks and benefits of breastfeeding in the context ofCOVID-19 infection, and are necessary to make evidence-based policies, and to care for these families.",2020,2022,UNIVERSITY OF ROCHESTER,282884,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C00928,3U01AI144616-02S1,Household Respiratory Virus SARS-CoV-2 Transmission and Immunity Sub-Study (HRTS),"The pandemic created by the novel human coronavirus SARS-CoV-2 has generated manyunanswered questions on the best practices for prevention and treatment for those with COVID-19 disease. The mechanism behind the lack of apparent disease susceptibility in children is alsounresolved. To answer these most critical questions, we require data on how the host immunesystem responds to SARS-CoV-2 infection and COVID-19 disease. Longitudinal cohortsestablished in naive populations are necessary for careful profiling of immune responses,disease severity, and the generation of protective memory. Disease presentation and outcomehas been highly variable among age groups and those with various underlying conditions,complicating study design. Large well-characterized human cohorts are costly to initiate anddifficult to develop quickly. In this study, we propose to use the DIVINCI Consortium cohorts,three geographically distinct human birth cohorts, which are already established andsuccessfully running to be able to immediately begin sampling individuals with suspected orconfirmed SARS-CoV-2 infection. Importantly, all three cohorts have the ability to collecthousehold samples, providing insights into immunity and disease progression across a broadage range. We propose to collect respiratory samples, breast milk, stool/rectal swab, andserum/PBMC samples, and from those samples, exhaustively assay the host immune responseto SARS-CoV-2. Based on the study design, we will be able to compare naive time points tothose during active infection as well as samples from individuals who remained asymptomaticcompared to those who develop varying degrees of symptoms. Our study proposes tocomprehensively measure immune cell populations in the peripheral blood in naive (baseline)samples and convalescent samples (after infection.) We propose to develop novel reagents formeasuring SARS-CoV-2-specific T and B cells. Further, we propose to measure SARS-CoV-2viral diversity and evolution. Finally, we will be able to extensively assay serological samples todetermine measurable differences in the response between individuals with mild and severeinfection and asymptomatic and symptomatic infection, and track their subsequent susceptibilityto re-infection. The DIVINCI consortium is uniquely situated to have immediate response to theSARS-CoV-2 pandemic with the ultimate goal of a more complete understanding of the virusand the disease.",2020,2022,ST. JUDE CHILDREN'S RESEARCH HOSPITAL,3686681,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00929,3U01AI152036-01S1,Characterizing the Immune Response to COVID-19 Infection in Atopic Dermatitis,"Great efforts are made in the face of the pandemic to understand anti-viral immune responses toCOVID-19/SARS-CoV-2. It is crucial to understand immune responses in moderate-to-severe atopic dermatitis(AD) patients who are on systemic immune-modulating medications and are infected with COVID-19. ADpatients(with and without asthma), are at increased risk for viral infections. Characterizing responses toCOVID-19 infection in AD patients may guide the way these patients are treated, and inform on whethertreatments need to be modified or discontinued in the instance of asymptomatic or symptomatic infections.Although some studies have shown that Th2 cytokines (among other cytokines) are elevated in severely illpatients admitted to ICUs with pneumonia secondary to COVID-19, no efforts have been published thus farevaluating the role of Th2 inflammation in severity of symptoms and outcomes in patients with COVID-19.Furthermore, the incidence and severity of COVID-19 symptoms among patients receiving Th2 blockade foratopic dermatitis with dupilumab, a monoclonal antibody targeting the IL-4/IL-13 signaling IL-4R receptor alphasubunit, has not been evaluated. It has long been believed that abnormally elevated Th2-axis polarization inthe setting of AD and asthma patients may negatively impact the ability of the immune system to induceappropriate Th1 response, as evidenced by the higher rate of viral infections in these patients. Also, as AfricanAmericans seem to be disproportionately affected by COVID-19, understanding if there are ethnic differencesin mounting COVID-19 responses in the setting of systemic and biologic treatments (i.e dupilumab), is crucial.This study is in scope to the parent award (RFA-AI-19-015), as we are an ADRN clinical site, and this studyfocuses on understanding COVID-19 in AD patients with different phenotypes based on ethnicity, treatmentand severity. We are requesting an administrative supplement under NOT-AI-20-031 to support this project. The hypothesis of this study is that Th2 blockade preferentially promotes a Th1-skewed anti-viralimmune response, leading to decreased or asymptomatic clinical severity with SARS-CoV-2/COVID-19infection. The aims of this study are: 1) To evaluate the incidence and severity of COVID-19 among patientscurrently treated for AD dupilumab (as compared to a group of AD patients treated with broad oral immunesuppressants); 2) To evaluate whether African American patients with AD on dupilumab have milder symptomsin the setting of COVID-19 compared to African American patients treated with other immune suppressants,and whether there are differences in mounting viral responses between patients of different ethnicities treatedwith dupilumab; 3) To evaluate and characterize immune responses in AD patients with reported symptoms ofCOVID-19 on dupilumab and other broad immunosuppressants using proteomic and transcriptomicapproaches.",2020,2022,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,244936,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility,2020 +C00930,3U01DA051126-01S1,National Drug Early Warning System (NDEWS) COVID-19 Supplement,"Parent Study: Through our parent U01, our National Drug Early Warning System (NDEWS) CoordinatingCenter aims to provide NIDA and the field with the most timely, salient, and valuable information on emergingsubstance use trends. By expanding data collection to include both former NDEWS sentinel sites as well asformer Community Epidemiology Workgroup (CEWG) sites, and by incorporating novel surveillance methodsto ensure early detection of signals of new psychoactive substances and known substances, our Early WarningNetwork extends geographic representation and provides a more complete picture of the size, direction, anddepth of substance use patterns in all US Census regions. We will use novel surveillance methods to ensureearly detection of signals indicating emerging drug trends and harmonize surveillance data across sentinel andCEWG sites. We will also conduct on-the-ground epidemiologic investigations on topics of immediate crisis orneed in order to provide functional feedback to impacted communities towards optimizing current and futureresponse, and we will disseminate results rapidly to the scientific community and the public alike. Proposed Supplement: The current COVID-19 crisis underscores a need for rapid assessments of the virus'simpact in substance-using populations throughout the NDEWS Early Warning Network, as people who usedrugs appear to be at increased risk for COVID-19-related adverse outcomes and may find it more difficult toget care during the crisis. In addition, COVID-19 may alter one's exposure to drug use, certain drugs, or mightchange patterns of drug use altogether. As an Early Warning System, NDEWS must be on the forefront of newtrends in drug use, drug-related mortality, and drug treatment utilization, all of which may be either directly orindirectly impacted by COVID-19. Although in-person human subjects research has been halted, COVID-19focused efforts that must begin now-with creative strategies that allow for immediate data to assess theimpact of COVID-19 on substance use behaviors. In this proposed study, we will (Aim 1) collect rapid responsedata on substance use-related consequences of COVID-19 from novel key informants across the country in theurban, rural, and suburban areas represented by the 18 Early Warning Network sites, focused on decedents,family members of decedents, and the community at large. Key informants will include 1) funeral directors(n=200), 2) emergency medical service personnel (n=200), and 3) syringe exchange workers (n=75). We will(Aim 2) detect trends in patterns of drug-related mortality, health services utilization, including overdosereversals, and syringe exchange services by following up with key informants at 2, 3, 4, and 5 months post-baseline. We will then (Aim 3) rapidly disseminate the data to NIDA, through media outreach, and contribute toscience through peer-reviewed publications. At a time when we cannot physically recruit or survey participantsin person due to the COVID-19 crisis, we believe this is an extraordinary opportunity to collect rich data fromkey informants nationwide. Results will provide targets for new research strategies and prevention efforts.",2020,2025,UNIVERSITY OF FLORIDA,130357,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Drug users | Sex workers,Emergency Responders | Social Workers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Approaches to public health interventions | Indirect health impacts,2020 +C00931,3U01HL123020-07S1,Preventive and Early Treatment of Acute Lung Injury Clinical Trials Network- Pgh - Supplement,"This project will create NHLBI COVID-19 common data elements and consensus outcomes toharmonize data practices across NHLBI and other COVID-19 studies. We will start withharmonizing data across two large NHLBI acute care clinical trial networks (PETAL, SIREN),and iterate, integrate, and promote these data harmonization standards with other COVID-19research groups, including the international REMAP-CAP platform trial and other NIH institutes.",2020,2021,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,322741,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C00932,3U19AI057229-17S1,"Influenza responses and repertoire in vaccination, infection and tonsil organoids.","Wuhan, China is the epicenter of a rapidly spreading pandemic the World Health Organization (WHO) hasofficially designated as COVID-19. COVID-19 is caused by SARS-CoV-2, but how it is spread from person toperson is still unclear. The asymptomatic presentation of the disease, and widespread travel out of Wuhan havepermitted its rapid dissemination. As of March 16, 2020, there are over 175,000 cases affecting 162 countrieswith over 6,700 fatalities worldwide. SARS-CoV-2 is positive-sense RNA virus infecting vertebrate hosts thatexists in a group of closely related co-evolving entities of which two others - SARS-CoV and MERS-CoV - havecaused recent epidemics. Due to the complexity of anti-viral immunity, experience with other viruses has shownthat swift success in vaccine development is by no means assured. A major challenge is the difficulty inadequately characterizing T cell-mediated recognition of viral epitopes. Finding the major shared specificities inCOVID-19 subjects will help us understand what the most important CD4+ and CD8+ T cell responses will be.These findings can be deployed to determine the optimal vaccine formulation so as to elicit these T cellspecificities. We hypothesize that T cell responses to specific epitopes of SARS-CoV-2 will be critical forits control in infected patients across diverse HLA haplotypes, and that a comprehensive mapping ofepitopes recognized by those who clear the virus and their cognate TCRs will facilitate the developmentof the most effective vaccines for COVID-19 treatment. To pursue this hypothesis, we will employ some verynew tools for T cell responses that have recently been developed at Stanford and the Princess Margaret CancerCenter, together with COVID-19 survivors' blood samples obtained in Toronto, Hong Kong and Stanford.",2020,2022,STANFORD UNIVERSITY,640459,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C00933,3U19AI057266-17S1,Vaccine Induced Immunity in the Young and Aged,"The over-arching goal of this proposal is to analyze SARS-CoV-2 antibody seroconversion rates in healthcare workers at the Emory University Hospital over the next year and to study adaptive immune responsesto SARS-CoV-2 infection during acute infection and at convalescence. These studies will draw on threemain sources of samples, either through an emerging infectious disease protocol at the Emory VaccineCenter Hope Clinic, through a sero-surveillance study initiated at Emory, and previously collected PBMCand serum samples from adult or elderly donors by Dr. Jorg Goronzy, respectively. We will develop andemploy a combination of antibody binding assays and viral neutralization assays to test the quantity andquality of the infection-induced antibody responses. This information will also be used to identify optimaldonors for single-cell antibody expression cloning, as we have previously described9-13. A recentlypurchased 10x instrument in our BSL3 facility at the Emory Vaccine Center will allow for a detailed analysisof the transcriptional profiles of innate and adaptive immune responses during acute SARS-CoV-2infection. The proposed studies will provide key insight into the dynamics of this devastating diseaseamong health care workers at a major metropolitan hospital in Atlanta. These efforts will also generate keyserological tools, provide an understanding of the humoral immune response to SARS-CoV-2 infection,and generate human monoclonal antibodies, with both diagnostic and therapeutic potential.",2020,2023,EMORY UNIVERSITY,506680,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Phase 2 clinical trial,2020 +C00934,3U19AI077439-13S1,UCSF COVID-19: Extended Immunophenotyping Studies,"We propose to rapidly apply key assays of patient samples derived from IMPACC studies tounderstand the critical features that characterize hospitalized patients with COVID-19, a pandemicdisease characterized by immune exacerbations of lung injury. These proposed studies are a naturaland focused extension of the work we are performing in the parent U19 award adapted to the urgentmedical need to better understand the pathogenesis of severe, life-threatening COVID-19 disease.We propose 5 site-specific studies that are highly complementary to assays being performed by theIMPACC national immunophenotyping cores here at UCSF and elsewhere. These include studiesthat focus on both airway cells and blood immune cells (including neutrophils) and utilize a set ofinnovative methods that allow for a detailed understanding of the nature and activation states ofspecific cell types within the airway and the blood. These studies promise to yield new insightsrelevant for understanding COVID-19 immunopathogenesis and predicting disease outcome andresponse to therapy, and could lead to novel therapeutic targets for this devastating disease.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,506680,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C00935,3U19AI077439-13S2,UCSF COVID-19 Immunophenotyping Clinical Study and Core Laboratories,"COVID-19, the pandemic illness caused by the novel virus SARS-CoV-2, is a serious respiratory illness thathas high infectivity and a mortality rate that varies from <1% to up to 20% depending on underlying risk factors.Indeed, disease severity varies markedly based on recognized clinical risk factors (age and co-morbidities).The biological underpinnings of this clinical variability are unknown but likely relate to variation in both the virusand the host response. A detailed understanding of the risk factors for severe disease, including genetic andenvironmental factors and the nature of the host immunological response, is essential for the development ofprognostic biomarkers and effective therapies. To meet this urgent need we propose to help develop and toparticipate in the IMPACC multi-center longitudinal clinical study of hospitalized patients with COVID-19 and toimmunophenotype participants using shared immunological methods that will be designed an carried out bycore laboratories at UCSF and at other participating institutions. Our specific aims are 1) to develop aprospective observational convenience cohort of adult subjects hospitalized with known or presumptiveCOVID-19, 2) to use this cohort to describe the relationship between specific immunologic assessments andclinical course of COVID-19 in hospitalized patients, and 3) to implement three core laboratories at UCSF tosupport immunophenotyping in this multicenter cohort. These core laboratories will perform bulk RNAsequencing of blood peripheral blood mononuclear cells (PBMC), bulk metagenomic next-generationsequencing (mNGS) on endotracheal aspirate samples, and serologic phage display assays (PhIP-Seq).Successful completion of these aims will yield critical information regarding the relationship between viral load,host immunological responses, and poor clinical outcomes that are urgently needed for biomarkerdevelopment and rational therapeutic targeting. In addition, the cellular samples banked in this study maydirectly contribute to the development of neutralizing antibodies and vaccine strategies that will be our ultimatedefense against recurrence of this extraordinary pandemic. A rapid and robust scientific and medical responseof the type proposed by the NIAID and the academic community in this consortium is an essential element of abroad response required to protect the health and well-being of all individuals, our health care system, and thebroader social structures that maintain global health and welfare.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,506680,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00936,3U19AI089992-09S1,Core for COVID-19 Cohort (IMPACC),"A core facility for the IMPACC study group will be formed to conduct analyses of samplescollected by the individual study sites. Shared protocols for subject enrollment and samplecollection have been established by the IMPACC study group. Collection and shipping to thecore site will be overseen by the Data Coordinating Center. Core assays will includemultiparameter single cell CyTOF of endotracheal aspirates and DNA sequencing. Corefunctions will be conducted in close collaboration with the IMPACC study group and includesample tracking and management, design of antibody labeling panel, sample processing andacquisition, DNA sequencing, initial data quality analysis and data sharing.",2020,2021,YALE UNIVERSITY,1087629,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00937,3U19AI089992-09S2,Shaw COVID-19 Supplement: Systems Immune Profiling of Divergent Responses to Infection,Not required by RFA,2020,2021,YALE UNIVERSITY,1087629,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00938,3U19AI089992-09S3,Immunophenotyping for COVID-19 Cohort (IMPACC),"In depth immunoprofiling of COVID-19 patients will be established to identify critical elements ofthe immune responses to the corona virus SARS-Co-V-2. This study is part of the IMPACCstudy group formed to conduct in depth analyses of samples from COVID-19 patients. Sharedprotocols for subject enrollment and sample collection have been established by the IMPACCstudy group to be collected across key time points of the disease. Our analysis will includebroad phenotyping of cell subsets and transcriptional responses of critical patient samples.Results will be assessed with the IMPACC study group bioinformatics team for integration withresults from IMPACC core facilities on the same samples such as bulk RNASeq, serumproteomics and metabolomics, DNA sequencing, and multiparameter single cell CyTOF ofendotracheal aspirates. Our studies to clarify and elucidate critical pathways in COVID-19pathogenesis and immune response will guide development of anti-viral therapeutics andvaccines to maximize resistance to the virus.",2020,2021,YALE UNIVERSITY,506680,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C00940,3U19AI100625-08S1,Systems Immunogenetics of Biodefense and Emerging Pathogens in the Collaborative Cross,"Abstract: Emerging viruses, such as SARS-CoV, influenza A virus (IAV), and West Nile virus (WNV) causehigh levels of morbidity and mortality in Human populations. Host immune responses can play either protectiveor a pathologic role during viral infections. Therefore, understanding of the regulatory networks and signalingpathways that determine the magnitude and quality of an individual's antiviral immune response has importantimplications for human health, since these genes/pathways could be therapeutically targeted to treat virus-induced disease, or may represent targets for enhancing the safety and efficacy of vaccines against a widerange of viral pathogens.Polymorphic host genes and regulatory networks have a major impact on immune response variation in humanpopulations. However, confounding environmental factors and/or ethical concerns limit the types of studiesthat can be conducted in humans. Therefore, genetically tractable model systems that capture the range ofgenetic and phenotypic diversity seen in humans, such as the Collaborative Cross (CC) are needed tomechanistically dissect the genetics of immune variation. Our research team has quantified variation inbaseline, as well as SARS-CoV, IAV, and WNV-induced immune responses in a panel of 110 CC RIX lines(reproducible F1 crosses between CC recombinant inbred (RI) lines that model heterozygous humanpopulations). To our knowledge, this represents to most comprehensive analysis of immune response variationever conducted in a genetic reference population, and in ongoing QTL mapping studies, we have identified100+ quantitative trait loci (QTL) associated with variation in virus-induced innate and adaptive immunity,inflammation and disease. Our program, which includes expertise in viral pathogenesis, innate and adaptiveimmunity, and quantitative genetics will use this unprecedented data base to: 1) identify and characterizepolymorphic host genes that drive variation in virus-induced disease, 2) test how interactions between differentpolymorphic genes/loci shape the host immune response, 3) test how these genes impact responses to otherviral pathogens, or function during allergy/auto-immunity, and 4) test the impact of these genes in the contextof human infections to identify targets for diagnosis, prevention and therapeutic interventions in humans.These studies will significantly enhance our understanding of how host genetic variation shapes virus-inducedimmunity and/or disease.",2020,2021,University of North Carolina at Chapel Hill,563507,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C00941,3U19AI104317-08S1,Human epidemiology and response to SARS-CoV-2 (HEROS),"PROJECT SUMMARY/ABSTRACT (from parent grant)The morbidity and cost to society from childhood viral respiratory illnesses (VRI) is staggering, and allergicrespiratory disease is rampant. In the search for prevention for these common and important diseases,perhaps the solutions are on the farm. Preliminary results from the Wisconsin Infant Study Cohort (WISC)demonstrate that children raised on farms have reduced VRI and atopic dermatitis, and distinct innate immunecell maturation trajectories in early life. Furthermore, in our preliminary studies mononuclear cells from Amishnewborns (high microbial exposure, low rates of allergy) had a more mature phenotype and enhanced antiviralresponses compared to WISC newborns. Collectively, these findings support our central hypothesis: farm-related microbial exposures are associated with increased immune cell maturation, decreased viralrespiratory illness severity, and decreased allergic sensitization. To address this hypothesis, we will enlistour currently enrolled 204 WISC participants (93 farm, 111 non-farm), and enroll additional Amish, WISC farm,and WISC non-farm families (50/group). Our study has three aims that employ cutting-edge technologies andleverage our investigative team's extensive experience with farm medicine, birth cohorts, respiratory virologyand immune development in children. Aim 1: To characterize how farm-related exposures relate to immunedevelopment in early life. We hypothesize that farm-related microbial exposures will prompt increased innateimmune cell maturation and function in early life, including enhanced anti-inflammatory mechanisms. In thesestudies, we will identify farming and microbial effects on immune development of key cells (epithelial cell,plasmacytoid dendritic cell, neutrophil, Tregulatory cells) in the mucosal response to viruses and allergens.Aim 2: To determine how farm exposures affect the burden of VRI and rates of allergic diseases. Wehypothesize that farm-exposed infants have reduced VRI burden and reduced sensitization to commonenvironmental allergens. In these studies, we will use viral diagnostics to determine infections and illnesses,and measure specific IgE to aeroallergens. Aim 3: To define group-specific associations between farm-relatedenvironmental and lifestyle factors, microbial exposure and colonization (nasopharyngeal and stool), immunedevelopment, and clinical outcomes (respiratory illness burden and rates of AD and allergic sensitization). Wehypothesize that house dust from farm homes, particularly Amish households, has more diverse environmentalmicrobiota communities, more diverse microbial colonization of the nasopharynx and gut, and improvedrespiratory health outcomes. In these studies, microbial genomics will be used to identify bacteria and fungi inhousehold dust, nasopharynx, and gut samples, and we will analyze relationships with patterns of immunedevelopment, VRI, and allergy. Completion of these studies will lead to development of novel strategies forenhancing immune development in early life to achieve primary prevention of VRI and allergic diseases.",2020,2021,UNIVERSITY OF WISCONSIN-MADISON,210586,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C00942,3U19AI111143-06S1,Tri-Institutional TB Research Unit: Persistence and Latency,"The COVID-19 pandemic has now spread from high- and middle-income countries to low-income countries,including Haiti and Tanzania. The natural history of COVID-19 is unknown in low-income countries. Wepropose to study a combined cohort of 3,054 adults in Haiti and Tanzania to determine the attack rate ofSARS-CoV-2 infection and severe COVID-19, to examine interactions with HIV infection, pulmonarytuberculosis, and hypertension in populations of African descent, and to determine long term cardiaccomplications of COVID-19. Cornell University has collaborated with the Groupe Haitien d'Etude du Sarcomede Kaposi et des Infections Opportunistes (GHESKIO) in Haiti for 38 years and for 15 years with the MwanzaIntervention Trials Unit (MITU) in Tanzania. The proposed emergency supplement leverages thesecollaborations and four established NIH-supported cohorts, which have already been enrolled, to addressNIAID priority areas. The specific aims are:1.To determine the incidence proportion of SARS-CoV-2 infection and the attack rate and risk factorsfor severe COVID-19, in well characterized cohorts of 3,054 adults from low-income communities inHaiti and Tanzania. Starting May 1, 2020 we will conduct monthly telephone interviews with the 3,054participants who are in active follow-up to record symptoms of COVID-19 during the pandemic. Participants willalso be encouraged to telephone us if they develop new symptoms. We have cell phone numbers for allcohort participants and have established procedures for telephone communication. We will also review hospitalrecords, perform verbal autopsies, and grade severity of COVID-19. We have banked sera from all participantscollected in 2016-2019. In September-November 2020 and again in March-May 2021, we will collect follow-upsera and perform serologic testing for the presence of anti-SARS-CoV-2 IgG antibodies. We will determine theodds for development of severe COVID-19 in participants who had HIV, TB, and hypertension.2. To determine the cardiac complications of SARS-CoV-2 infection in 1,909 adults with known baselinecardiac function. In 1,909 patients who previously had baseline EKGs and echocardiograms (2016-2019), wewill repeat cardiac echo and EKG in 2021 to quantify the odds for development of incident left ventricularsystolic dysfunction in those who did and did not become SARS-CoV-2 infected. LV function will be quantifiedby global longitudinal strain. We will also determine incidence of right ventricular systolic dysfunction,pulmonary hypertension and segmental wall motion abnormalities by echocardiogram, and new Q-waves andother abnormalities on EKG.Defining viral infection rates and natural history in low-income countries will be critical for future preventioninterventions. Determining risk for people with HIV, TB, and hypertension will improve their care andprevention. Understanding cardiac sequelae of SARS-CoV-2 will improve care for COVID-19 survivors.",2020,2021,Weill Cornell Medicine - Cornell University,353106,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Africa | Americas,,,,United States of America,Haiti | Tanzania,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C00943,3U19AI111825-07S1,Characterization of the antibody responses elicited upon SARS-CoV-2 infection,"AbstractExtensive research on the basic immunological mechanisms that drive human immunity has provided the generalframework by which the human immune system responds to foreign antigens. However, it is well-appreciatedthat each viral infection poses unique challenges to the immune system and the elicited immune responses arecharacterized by substantial heterogeneity that impacts disease susceptibility and pathogenesis, by conferringeither protective or disease-enhancing activities. The ongoing COVID-19 pandemic represents a significantthreat for global public health with tremendous socio-economic consequences. Early clinical and epidemiologicaldata from COVID-19 patients suggest that while for the majority of the population, SARS-CoV-2 infection causesmild symptoms that usually resolve within a few weeks, a substantial fraction of patients develops severe, oftenlife-threatening, clinical complications, including acute respiratory distress syndrome and pneumonia.Differences in the induction of protective antiviral immunity likely accounts for the differential susceptibility tosevere disease upon SARS-CoV-2 infection. Understanding the heterogeneity of immune responses elicitedupon SARS-CoV-2 infection is therefore critical for characterizing the immune mechanisms that confer protectionagainst COVID-19 disease, guiding the development of novel therapeutics for disease control, as well as,determining disease susceptibility in high-risk populations. The proposed studies aim to characterize theantibody responses that are elicited upon infection with SARS-CoV-2, determining the breadth of antibodyspecificities, neutralization potency, as well as Fc domain heterogeneity of anti-SARS-CoV-2 IgG antibodies.More specifically, we plan to recruit recovered COVID-19 patients and systematically analyze their B-cellresponses to determine their transcriptomic profile, as well as the functional properties of their B-cell receptors.In parallel, serologic studies from these individuals aim to characterize the breadth and potency of theirneutralization activity and determine the subclass and Fc glycan distribution of anti-SARS-CoV-2 antibodies.Additionally, Fc domain function will be assessed in well-established ADCC, ADCP, and ADE assays to evaluatethe capacity of anti-SARS-CoV-2 IgG antibodies to confer protective or pathogenic activities. Follow-up serologicstudies will be performed in a large cohort of patients with variable disease severity, ranging from asymptomaticto severe symptomatic cases, to determine the functional activity of elicited anti-SARS-CoV-2 antibodies andassess their Fc domain heterogeneity and effector function. These studies are within the scope of our parentgrant, as they are focused on the understanding of the immune responses that are elicited during viral infection.We anticipate that the findings of these studies will provide novel insights into the immunological mechanismsthat confer protection or susceptibility to COVID-19 disease, accelerating our efforts for the development ofvaccine or therapeutic interventions for the control of SARS-CoV-2 infection.",2020,2022,ROCKEFELLER UNIVERSITY,1500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00944,3U19AI116484-05S1,Human Lung Organoid Models of SARS-CoV-2 Infection,"ABSTRACTPrimary human organoid models are an increasingly deployed platform for in vitro infectious disease modeling.The COVID-19 pandemic, engendered by the novel coronavirus SARS-CoV-2, represents a grave threat topublic health and physiologic in vitro infection models are therefore urgently needed. This supplement requestfor U19AI116484, Stanford Cooperative Center for Novel, Alternative Model Systems for Enteric Diseases(Stanford NAMSED), requests funding to create new models for SARS-CoV-2 infection using novel human lungorganoid technologies in collaboration with Dr. Ralph Baric at UNC, a recognized coronavirus authority. Thesestudies exploit SARS-CoV-2 infection of organoids using a feeder-free, chemically defined human lung organoidsystem (Calvin Kuo lab), lung organoids with integrated immune components (Calvin Kuo), methods for robustapical-basal inversion of lung organoid polarity (Manuel Amieva), BSL3 single cell RNA-seq (Catherine Blish)and SARS-CoV-2-GFP indicator strains and BSL3 facilities (Ralph Baric). The SARS-CoV-2 infection of lungorganoids will occur in BSL3 containment at both UNC and Stanford to compare apical versus basal infectionroutes, document how epithelial infection initiates secondary immune responses, and overall generate improved3D physiological models of SARS-CoV-2-GFP infection relevant to therapeutics screening.",2020,2021,STANFORD UNIVERSITY,900000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2020 +C00945,3U19AI118608-04S1,IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC): Clinical and Data Coordinating Center (CDCC),"IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC): Clinical and Data CoordinatingCenter (CDCC)Project summaryIn December 2019, a cluster of respiratory illness in Wuhan, China defined the onset of a global pandemicinvolving a novel coronavirus (SARS-CoV-2) with associated respiratory disease (COVID-19). There are majorresearch efforts underway to understand SARS-CoV-2 infections and the associated COVID-19 disease. TheIMmunoPhenotyping Assessment Covid-19 Cohort (IMPACC) surveillance study is based upon an observationalcohort that will collect detailed clinical, laboratory, and radiographic data in coordination with biologic samplingof blood and respiratory secretions and viral shedding in nasal secretions. The goal of the surveillance study isto identify immunophenotypic and genomic features of COVID-19-related susceptibility and/or progression.The IMPACC Clinical and Data Coordinating Center (CDCC) will provide clinical and data coordination supportfor the IMPACC study. This includes comprehensive study coordination and project management support acrossall participating IMPACC clinical and Core laboratory sites, including initial site training and ongoing study supportthrough the completion of study enrollment and follow-up. The CDCC will provide clinical sites with real-timesample tracking and data capture capabilities, including all necessary supplies and reagents for samplecollection, electronic case report forms (eCRFs) for data entry, and quality control/quality assurance (QC/QA)processes to ensure high quality sample collection and data capture. Finally, the CDCC will design digitalinfrastructure components to facilitate data management, data storage, and data analysis of study endpoint andsafety data, including interim and final analysis of primary endpoints, ongoing safety and outcome monitoring,and bioinformatics analytic support for secondary/exploratory endpoints.",2020,2021,BOSTON CHILDREN'S HOSPITAL,2426447,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Disease pathogenesis",2020 +C00946,3U19AI118608-04S2,IMmunoPhenotyping Assessment of a Covid-19 Cohort (IMPACC): Clinical Site,"PROJECT SUMMARY:From a cluster of respiratory illnesses in Wuhan, China, to a worldwide pandemic, the world has learned of anovel coronavirus (SARS-CoV-2) but little is known about the pathogenesis that leads to the disease termed""COVID"". Patients with SARS-CoV-2 infection range from asymptomatic, mild, moderate, to severe infections,resulting in ICU hospitalization and even death. In the US alone, there is a prediction of ~100,000 - 240,000deaths from SARS-CoV-2 infections. There is an urgent need to immunophenotype patients with COVID todefine biomarkers of disease severity and outcome to inform new interventions to prevent or treat this deadlydisease. Key to characterizing the human immune response to SARS-CoV-2, is recruitment , enrollment andretention of a cohort of study participants with COVID. To this end, we will employ best practices in clinicalresearch to pursue three Specific Aims (SAs). In SA1, we will recruit and enroll a well-defined cohort of adultswith SARS-CoV-2 (COVID-19); in SA2, we will obtain and store biosamples from patients in this COVID-19cohort in support the NIAID immunophenotyping effort and in SA3 we will partner with the Clinical & DataCoordinating Center (CDCC) to provide clinical data from this COVID-19 cohort to ensure these samples arehighly annotated with key clinical data.Overall, successful pursuit of these SAs will provide well defined clinical samples and high qualityclinical data to support the NIAID COVID immunophenotyping effort.",2020,2021,BOSTON CHILDREN'S HOSPITAL,184957,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00947,3U19AI118608-04S3,COVID-19 Immunophenotyping Proteomics and Metabolomics Core (PMC),"Project Summary/AbstractIn Dec 2019, a cluster of respiratory illness in Wuhan China defined the onset of a worldwide pandemic involvinga novel coronavirus (SARS-CoV-2). SARS-CoV-2 infected patients are frequently asymptomatic, but initialepidemiologic estimates from the WHO indicate that ~15% of patients develop severe disease including viralpneumonia often requiring ICU care due to progression to develop life-threatening complications including (butnot limited to) shock and secondary organ failures, and super-infections. Risk factors for increased mortality fromCOVID-19 include older age, COPD, ischemic heart disease, diabetes mellitus, and immunosuppression.Although direly needed, no targeted therapies or vaccinations are available as of now. Major research effortshave been launched towards the development of anti-SARS-CoV-2 vaccines, including those within BostonChildren's Hospital's Precision Vaccines Program. To facilitate and accelerate these therapy and vaccinationdevelopment efforts, more detailed immunophenotyping and understanding of the host immune response toSARS-CoV-2 are required. This knowledge may inform prognostication of resolution of infection versus diseaseprogression and identify the relevant targets for potential therapeutic interventions. Overall, the outcomes ofthese immunophenotyping maps are critical for identifying and prioritizing host-directed interventions to limit ormitigate disease progression. Based on this rationale, we hypothesize that plasma proteomics and metabolomicsfrom hospitalized COVID-19 patients, longitudinally collected during the hospital stay and during the subsequentconvalescence period of up to one year post-discharge from the hospital will provide much needed insights intothe intricacies of the immunophenotype of COVD19 patients. Thus, they will be crucial to support NIAID's effortstowards enabling and accelerating therapy and vaccine development. To this end, we propose a Proteomics andMetabolomics Core (PMC) to support NIAID's efforts to characterize at the molecular and cellular level theimmunophenotype associated with COVID-19.The PMC will quantitative map the global plasma proteome (Specific Aim 1) and the global plasma metabolome(Specific Aim 2), followed by hypothesis-driven targeted metabolomics to detect metabolites and metabolicpathways that play a role in the COVID-19 disease progression (Specific Aim 3). All plasma samples will belongitudinally collected from COVID-19 patients upon hospitalization and the following 28 days in the hospital aswell as the subsequent convalescence period of up to 12 months after discharge.We anticipate that the PMC will make substantial contributions to confronting the new COVID-19 pandemic, forwhich therapeutic strategies and vaccines must be developed rapidly. The PMC will help portray a broad profileof the changes that occur in COVID-19 patients and that are associated with disease severity, progression andrecovery to support the quest for anti-COVID-19 therapies and vaccines.",2020,2021,BOSTON CHILDREN'S HOSPITAL,2174014,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C00948,3U19AI118608-04S4,IMmunoPhenotyping Assessment of a Covid-19 Cohort (IMPACC): Immunophenotyping of innate and adaptive immune response to SARS-CoV-2 infection,"LAS PROJECT SUMMARY:From a cluster of respiratory illnesses in Wuhan, China, to a worldwide pandemic, the world has learned of anovel coronavirus (SARS-CoV-2) but little is known about the pathogenesis that leads to the disease termed""COVID"". Patients with SARS-CoV-2 infection range from asymptomatic, mild, moderate, to severe infections,resulting in ICU hospitalization and even death. In the US alone, there is a prediction of ~100,000 - 240,000deaths from SARS-CoV-2 infections. There is an urgent need to 1) characterize the host innate and adaptiveresponse to SARS-CoV-2 and 2) to define immunologic biomarkers that can inform new approaches fordiagnostic, prognostic, therapeutic and preventative (e.g., vaccine) modalities in order to improve our ability totreat and prevent disease.To enhance the efficiency of immuophenotyping, the Precision Vaccines Program (PVP) has optimized a numberof sample-sparing in vitro assays to characterize both innate and adaptive immune function. These establishedassays will be applied to the evaluation of SARS-CoV-2 infections and identification of biomarkers associatedwith morbidity and mortality, which remains an unmet need and a research priority for the fight against COVID.Through investigating soluble and cellular innate and adaptive immune mediators, we will gain insight into thecontrol of inflammation and infection in COVID. In Specific Aim 1 (SA1), we will measure, eg, (a) the plasmaenzyme adenosine deaminase (ADA) that metabolizes the anti-inflammatory metabolite adenosine to theimmunologically inert inosine, thereby enhancing Th1 immune responses and enhancing antiviral innate andadaptive immunity; and (b) human defensins, antimicrobial peptides that enhance innate antiviral (e.g., IFN) andneutralizing antibody (Ab) responses to coronaviruses. In SA2, we will employ system serology, to furthercharacterize Ab function and efficiency to SARS-CoV-2 across the severity of infection. In SA3, we will measureresponses of whole blood leukocytes to activation of pathogen recognition receptors (PRRs) as well asresponses of T-cell co-cultures to SARS-CoV-2 spike protein antigen.Overall, successful completion of the proposed IMPACC Local Assay Site studies will provide unique insightsinto human innate and adaptive immune responses to SARS-CoV-2 in relation to COVID progression andprognosis. These insights will provide fresh approaches to develop diagnostics, therapeutics and preventativemeasures against COVID-19, including vaccines.",2020,2021,BOSTON CHILDREN'S HOSPITAL,308143,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C00949,3U19AI128910-03S1,HIPC-COVID:Immunophenotyping Study - Supplement 1: HIPC - Clinical Sample Collection and Processing,"Summary:The goal of the Administrative Supplement is to provide a central rich store of data and specimensfrom two independent cohorts located in Reading, Pennsylvania and Cleveland, Ohio. Thesamples and the clinical data will be distributed to the central cores assigned by the programwhere standardized phenotypic assays will be performed. General leadership of the Cores will beprovided by Dr. Charles Cairns from Drexel University for the Reading cohort and Dr. Benignofrom Case Western Reserve University.There are 3 aims of this Administrative supplement.Specific Aim 1: To provide biological specimens (PBMCs, sputum, and lavages) to all ourdesignated cores in order to characterize the immunophenotypes and the immune status andresponse to COVID-19 infection.Specific Aim 2: To provide clinical data (CBC counts, clinical tests, imaging) to all our designatedcores in order to establish correlation with immune status and disease progressionSpecific Aim 3: To provide biological specimens and clinical data to our assigned laboratories atDrexel and Case Western Universities. These laboratories will perform unique assays that are notcovered by the core laboratories of the program.",2020,2021,DREXEL UNIVERSITY,852570,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00950,3U19AI128913-03S1,Mapping Immune Responses to CMV in Renal Transplant Recipients - Clinical Core,"ABSTRACTThe COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significantmorbidity and mortality in previously healthy patients. A significant observation is that although this infectionmay result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patientsexperience progression of respiratory symptoms to requirement of intubation for mechanical respiratorysupport and death due to severe respiratory failure. This clinical observation strongly suggests that differencesin host immunologic response are the determinative factor in clinical outcome. We hypothesize that theproposed systems immunology, biostatistical and computational modeling approaches, coupled with detailedclinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplaybetween SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess thefrequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonalityof their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immuneresponse to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation-based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resourceof highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development ofnovel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.",2020,2021,University of California-Los Angeles,869489,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C00951,3U19AI128913-03S2,Mapping Immune Responses to CMV in Renal Transplant Recipients - Mechanistic Assays Core,"ABSTRACTThe COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significantmorbidity and mortality in previously healthy patients. A significant observation is that although this infectionmay result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patientsexperience progression of respiratory symptoms to requirement of intubation for mechanical respiratorysupport and death due to severe respiratory failure. This clinical observation strongly suggests that differencesin host immunologic response are the determinative factor in clinical outcome. We hypothesize that theproposed systems immunology, biostatistical and computational modeling approaches, coupled with detailedclinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplaybetween SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess thefrequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonalityof their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immuneresponse to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation-based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resourceof highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development ofnovel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.",2020,2021,University of California-Los Angeles,222841,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00952,3U19AI142742-02S1,Functional and dysfunctional human CD4 T cell and B cell responses to bacteria and viruses,"PROJECT SUMMARYOverall ComponentCOVID19 is a severe ongoing pandemic. Our understanding of the immune response to this disease is lacking,which impairs both the development of proper therapeutics and a vaccine. Vaccines are one of the most costeffective and extraordinarily successful medical interventions. Most of those vaccines depend on CD4 T+ cellsand their help to B cells. We have developed multiple new techniques to study human CD4+ T cells over the pastseveral years, which have have been implementing in our LJI CCHI. The supplement proposed here will facilitaterapid and vigorous pursuit of an understanding of the T cell responses to SARS-CoV2 in humans, which mayhelp in the development of treatments and vaccines for COVID19.",2020,2021,LA JOLLA INSTITUTE FOR IMMUNOLOGY,982950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C00954,3U24DA041123-06S1,ABCD-USA Consortium: Data Analysis Center,"AbstractAdolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and childhealth in the United States. ABCD consists of a Coordinating Center, a Data Analysis and InformaticsResource Center, and 21 research sites across the U.S. ABCD has enrolled a diverse sample of 11,878 9-10year-olds, and is tracking their biological and behavioral development through adolescence into youngadulthood. All participants receive repeated state-of-the-art neuroimaging, neuropsychological testing,bioassays, and detailed youth and parent assessments of substance use, mental health, physical health, andculture and environment.In March 2020, when our participants are ages 11-13, the world became substantially affected by the COVID-19 pandemic, leading to an upheaval in the economy and the lives of almost every family. The majority of U.S.schools closed to reduce viral spread. Many parents incurred changes in work (from home, longer shifts,reduced wages, and/or job loss), some services and support systems became disrupted, and case counts anddeath tolls surge. The massive multifaceted impact of this unprecedented event has the potential to affect fordecades those who are currently children. The proposed research immediately leverages the ABCD cohort,infrastructure, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on eachchild in the study. By collecting this situational information as soon as possible, we can use existing ABCD datato examine perturbations in developmental trajectories of brain functioning, cognition, substance use,academic achievement, social functioning, and physical and mental health.The proposed project would query all ABCD participants and their parents multiple times about the impact ofthe pandemic on their lives and, in a subset of participants, examine their physical activity and sleep objectivelywith activity trackers (Fitbits), over the months of school closures, job loss, and disease spread. This will allowthe consortium and scientific community at large to test multiple aims regarding how various facets of thepandemic affect development. This includes: (1) characterizing the impact of the COVID-19 pandemic on brainand cognitive development and onset of substance use; (2) evaluating the extent to which alternative schoolingapproaches exacerbate or mitigate the impact of the pandemic on brain and cognitive development andsubstance use outcomes; and (3) evaluating the extent to which family stressors exacerbate or mitigate theimpact of the pandemic on neurobiological, cognitive, and substance use outcomes. This unprecedented crisisprovides an opportunity to make use of ABCD's elaborate infrastructure and rigorous scientific processes todiscern critical dimensions of development not previously envisioned.",2020,2027,UNIVERSITY OF CALIFORNIA-SAN DIEGO,157500,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2015 +C00955,3U24DA041147-06S1,ABCD-USA Consortium: Coordinating Center,"AbstractAdolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and childhealth in the United States. ABCD consists of a Coordinating Center, a Data Analysis and InformaticsResource Center, and 21 research sites across the U.S. ABCD has enrolled a diverse sample of 11,878 9-10year-olds, and is tracking their biological and behavioral development through adolescence into youngadulthood. All participants receive repeated state-of-the-art neuroimaging, neuropsychological testing,bioassays, and detailed youth and parent assessments of substance use, mental health, physical health, andculture and environment.In March 2020, when our participants are ages 11-13, the world became substantially affected by the COVID-19 pandemic, leading to an upheaval in the economy and the lives of almost every family. The majority of U.S.schools closed to reduce viral spread. Many parents incurred changes in work (from home, longer shifts,reduced wages, and/or job loss), some services and support systems became disrupted, and case counts anddeath tolls surge. The massive multifaceted impact of this unprecedented event has the potential to affect fordecades those who are currently children. The proposed research immediately leverages the ABCD cohort,infrastructure, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on eachchild in the study. By collecting this situational information as soon as possible, we can use existing ABCD datato examine perturbations in developmental trajectories of brain functioning, cognition, substance use,academic achievement, social functioning, and physical and mental health.The proposed project would query all ABCD participants and their parents multiple times about the impact ofthe pandemic on their lives and, in a subset of participants, examine their physical activity and sleep objectivelywith activity trackers (Fitbits), over the months of school closures, job loss, and disease spread. This will allowthe consortium and scientific community at large to test multiple aims regarding how various facets of thepandemic affect development. This includes: (1) characterizing the impact of the COVID-19 pandemic on brainand cognitive development and onset of substance use; (2) evaluating the extent to which alternative schoolingapproaches exacerbate or mitigate the impact of the pandemic on brain and cognitive development andsubstance use outcomes; and (3) evaluating the extent to which family stressors exacerbate or mitigate theimpact of the pandemic on neurobiological, cognitive, and substance use outcomes. This unprecedented crisisprovides an opportunity to make use of ABCD's elaborate infrastructure and rigorous scientific processes todiscern critical dimensions of development not previously envisioned.",2020,2027,UNIVERSITY OF CALIFORNIA-SAN DIEGO,157500,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2015 +C00956,3U24DA041147-06S1,ABCD-USA Consortium: Coordinating Center,"AbstractAdolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and childhealth in the United States. ABCD consists of a Coordinating Center, a Data Analysis and InformaticsResource Center, and 21 research sites across the U.S. ABCD has enrolled a diverse sample of 11,878 9-10year-olds, and is tracking their biological and behavioral development through adolescence into youngadulthood. All participants receive repeated state-of-the-art neuroimaging, neuropsychological testing,bioassays, and detailed youth and parent assessments of substance use, mental health, physical health, andculture and environment.In March 2020, when our participants are ages 11-13, the world became substantially affected by the COVID-19 pandemic, leading to an upheaval in the economy and the lives of almost every family. The majority of U.S.schools closed to reduce viral spread. Many parents incurred changes in work (from home, longer shifts,reduced wages, and/or job loss), some services and support systems became disrupted, and case counts anddeath tolls surge. The massive multifaceted impact of this unprecedented event has the potential to affect fordecades those who are currently children. The proposed research immediately leverages the ABCD cohort,infrastructure, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on eachchild in the study. By collecting this situational information as soon as possible, we can use existing ABCD datato examine perturbations in developmental trajectories of brain functioning, cognition, substance use,academic achievement, social functioning, and physical and mental health.The proposed project would query all ABCD participants and their parents multiple times about the impact ofthe pandemic on their lives and, in a subset of participants, examine their physical activity and sleep objectivelywith activity trackers (Fitbits), over the months of school closures, job loss, and disease spread. This will allowthe consortium and scientific community at large to test multiple aims regarding how various facets of thepandemic affect development. This includes: (1) characterizing the impact of the COVID-19 pandemic on brainand cognitive development and onset of substance use; (2) evaluating the extent to which alternative schoolingapproaches exacerbate or mitigate the impact of the pandemic on brain and cognitive development andsubstance use outcomes; and (3) evaluating the extent to which family stressors exacerbate or mitigate theimpact of the pandemic on neurobiological, cognitive, and substance use outcomes. This unprecedented crisisprovides an opportunity to make use of ABCD's elaborate infrastructure and rigorous scientific processes todiscern critical dimensions of development not previously envisioned.",2020,2027,UNIVERSITY OF CALIFORNIA-SAN DIEGO,50000,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2015 +C00957,3U24DA041147-06S1,ABCD-USA Consortium: Coordinating Center,"AbstractAdolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and childhealth in the United States. ABCD consists of a Coordinating Center, a Data Analysis and InformaticsResource Center, and 21 research sites across the U.S. ABCD has enrolled a diverse sample of 11,878 9-10year-olds, and is tracking their biological and behavioral development through adolescence into youngadulthood. All participants receive repeated state-of-the-art neuroimaging, neuropsychological testing,bioassays, and detailed youth and parent assessments of substance use, mental health, physical health, andculture and environment.In March 2020, when our participants are ages 11-13, the world became substantially affected by the COVID-19 pandemic, leading to an upheaval in the economy and the lives of almost every family. The majority of U.S.schools closed to reduce viral spread. Many parents incurred changes in work (from home, longer shifts,reduced wages, and/or job loss), some services and support systems became disrupted, and case counts anddeath tolls surge. The massive multifaceted impact of this unprecedented event has the potential to affect fordecades those who are currently children. The proposed research immediately leverages the ABCD cohort,infrastructure, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on eachchild in the study. By collecting this situational information as soon as possible, we can use existing ABCD datato examine perturbations in developmental trajectories of brain functioning, cognition, substance use,academic achievement, social functioning, and physical and mental health.The proposed project would query all ABCD participants and their parents multiple times about the impact ofthe pandemic on their lives and, in a subset of participants, examine their physical activity and sleep objectivelywith activity trackers (Fitbits), over the months of school closures, job loss, and disease spread. This will allowthe consortium and scientific community at large to test multiple aims regarding how various facets of thepandemic affect development. This includes: (1) characterizing the impact of the COVID-19 pandemic on brainand cognitive development and onset of substance use; (2) evaluating the extent to which alternative schoolingapproaches exacerbate or mitigate the impact of the pandemic on brain and cognitive development andsubstance use outcomes; and (3) evaluating the extent to which family stressors exacerbate or mitigate theimpact of the pandemic on neurobiological, cognitive, and substance use outcomes. This unprecedented crisisprovides an opportunity to make use of ABCD's elaborate infrastructure and rigorous scientific processes todiscern critical dimensions of development not previously envisioned.",2020,2027,UNIVERSITY OF CALIFORNIA-SAN DIEGO,100000,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2015 +C00958,3U24DA041147-06S1,ABCD-USA Consortium: Coordinating Center,"AbstractAdolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and childhealth in the United States. ABCD consists of a Coordinating Center, a Data Analysis and InformaticsResource Center, and 21 research sites across the U.S. ABCD has enrolled a diverse sample of 11,878 9-10year-olds, and is tracking their biological and behavioral development through adolescence into youngadulthood. All participants receive repeated state-of-the-art neuroimaging, neuropsychological testing,bioassays, and detailed youth and parent assessments of substance use, mental health, physical health, andculture and environment.In March 2020, when our participants are ages 11-13, the world became substantially affected by the COVID-19 pandemic, leading to an upheaval in the economy and the lives of almost every family. The majority of U.S.schools closed to reduce viral spread. Many parents incurred changes in work (from home, longer shifts,reduced wages, and/or job loss), some services and support systems became disrupted, and case counts anddeath tolls surge. The massive multifaceted impact of this unprecedented event has the potential to affect fordecades those who are currently children. The proposed research immediately leverages the ABCD cohort,infrastructure, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on eachchild in the study. By collecting this situational information as soon as possible, we can use existing ABCD datato examine perturbations in developmental trajectories of brain functioning, cognition, substance use,academic achievement, social functioning, and physical and mental health.The proposed project would query all ABCD participants and their parents multiple times about the impact ofthe pandemic on their lives and, in a subset of participants, examine their physical activity and sleep objectivelywith activity trackers (Fitbits), over the months of school closures, job loss, and disease spread. This will allowthe consortium and scientific community at large to test multiple aims regarding how various facets of thepandemic affect development. This includes: (1) characterizing the impact of the COVID-19 pandemic on brainand cognitive development and onset of substance use; (2) evaluating the extent to which alternative schoolingapproaches exacerbate or mitigate the impact of the pandemic on brain and cognitive development andsubstance use outcomes; and (3) evaluating the extent to which family stressors exacerbate or mitigate theimpact of the pandemic on neurobiological, cognitive, and substance use outcomes. This unprecedented crisisprovides an opportunity to make use of ABCD's elaborate infrastructure and rigorous scientific processes todiscern critical dimensions of development not previously envisioned.",2020,2027,UNIVERSITY OF CALIFORNIA-SAN DIEGO,164017,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2015 +C00959,3U45ES006180-28S1,UAW NIEHS Worker Training Program Coronavirus and Infectious Disease Response Training (Admin Supp Clinical Trial Not Allowed),"Project Summary/Abstract The International Union, UAW and its partners propose to conduct training to prevent andreduce exposure to SARS-CoV-2 among healthcare workers, emergency first responders,manufacturing workers, and members of underserved Hispanic/Latino communities. Theparamount goal of this project is to provide workers and members of underserved populationsidentified above with the knowledge, information and skills that they need to protect themselvesfrom Covid-19 and to work with employers and community institutions to establish andimplement programs that will protect them from Covid-19. The specific aims of this proposalare: To modify the NIEHS training tool Protecting Yourself from Covid-19 In the Workplace,using material from previously developed UAW curricula on infectious diseases and make itavailable online. To conduct remote train-the-trainers (TTT) that will train UAW staff and worker-trainers todeliver Covid-19 training and will train them in the use of online platforms for training. To have staff and worker-trainers conduct industry-specific awareness level TTTs forworkplace health and safety representatives, health and safety committees and other local unionleaders responsible for workplace health and safety. To assist local unions and UAW-represented workplaces and UAW consortium partners toidentify hardware and software needs for conducting remote training and to develop realisticplans to meet those needs given available resources. To conduct a remote train-the-trainer (TTT) that will train consortium partners to deliverCovid-19 training. To add a Covid-19 unit to our 40-hour Industrial Emergency Response (IER) techniciantraining, modify the training for delivery online, and deliver one online 40-hour IER class. To modify the NIEHS resiliency training for delivery online and deliver it to UAW members,staff, worker-trainers and UAW health and safety reps to help deal with the emotional straincaused by the pandemic and by responding to it. To conduct program evaluation of all of the above, making use of worker-evaluators, wherepossible, to provide feedback for continual improvement of curricula and delivery methods.",2020,2020,"INTERNATIONAL UNION, UAW OF AMER AFL-CIO",199584,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,Health service delivery,2020 +C00960,3U45ES019360-10S1,Hazardous Materials Worker Health and Safety Training (U45) Cooperative Agreement,"ABSTRACTThe Texas-Utah Consortium will address an immediate and critical need to prevent or reduceoccupational exposure to the SARS-CoV-2 virus. Composed of dedicated experts in medicine, publichealth, industrial hygiene, epidemiology and education, the Texas-Utah Consortium advances theNational Institute of Environmental Health Sciences Worker Training Program's objective to reduce work-related harm and improve disaster preparedness and response.The Texas-Utah Consortium serves as a resource for workers, responders, and residents across thecountry with a targeted focus on the population of United States Department of Health and HumanServices Public Health Regions 5, 6, and 8. In this supplemental application, the Consortium proposes toreduce and prevent occupational exposures to COVID-19 in workers responding to the pandemic and inworkers returning to the physical worksite. The Consortium will accomplish this by creating a portfolio ofonline training courses that are practical, specific, rooted in sound public health principles, and basedon current scientific knowledge relating to COVID-19. The Consortium places special emphasis ontraining workers in the essential services that are critical to maintaining the nation's infrastructure.Additionally, this training is responsive to the changing needs of employees returning to the physicalworksite. Consortium experts will work with instructional developers to adjust current curricula andcreate new course content in response to current crisis standards and stockpile shortages.Building on past successes and using evidence-based teaching techniques, the Consortium projectstraining about 500 workers within a 10-week project period. The public health impact of the Texas-UtahConsortium is a knowledgeable workforce and community with the skills and confidence to recognize andmitigate COVID-19 exposures in the workplace.",2020,2020,The University of Texas Health Science Center at Houston,98444,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2020 +C00961,3U54EB027049-02S1,The Center for innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern University (C-THAN) Supplemental Request,"The ""C-THAN POCTRN COVID-19 Proposal"" is a supplement to the existing Center for innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern (C-THAN) which aims to support development oftechnologies which can help address the urgent healthcare needs created by the COVID-19 pandemic. Theextent and urgency of the situation requires an aggressive and innovative approach to accelerate the deliveryof solutions to address immediate and future needs. Our approach augments the strong technical and clinicalexpertise within our own and the existing four POCTRN centers and their Coordinating Center. The specificaims are: 1) develop a SARS-CoV-2 ten-minute molecular diagnostic test based on the Minute MolecularPlatform; and 2) scale up C-THAN's established international network for COVID-19 technologicaldevelopment and testing of relevant products and assays in sub-Saharan Africa and other low- and middle-income countries (LMICs). For aim 1, C-THAN proposes the development of a ten-minute SARS-CoV-2 testfor the Minute Molecular DASH (Diagnosis Analyzer for Selective Hybridization), a sample-to-answer platformfor point-of-care use in medical clinics, emergency departments and urgent care centers. The DASH platformexploits novel fast PCR and microfluidic fabrication technologies developed at the Center for innovation inGlobal Health Technologies (CIGHT) at Northwestern University. DASH technology can be adapted for highthroughput uses such as airports, hospitals, nursing homes, emergency departments and drive-through testingsites. For aim 2, we will scale up C-THAN resources to expand addressing the impact of the pandemic. TheC-THAN network consists of four biomedical engineering (BME) technology development sites plus threeclinical validation/needs assessment sites. The BME sites include University of Cape Town and StellenboschUniversity in South Africa, and University of Lagos and University of Ibadan in Nigeria. The seven clinicalvalidation/needs assessment sites include ones located with the engineering sites plus at University of Jos inNigeria, University of Bamako in Mali and Muhimbili University in Tanzania. The relationship of these sites withNorthwestern University go back up to 22 years. We will utilize Northwestern's Institute for Global HealthCatalyzer Award Program which has been funding promising research projects addressing critical global healthneeds for over 10 years. Two weeks ago, the Institute redirected all proposals to address only COVID-19activities. Basic scientists, biomedical engineers, infectious diseases specialists, virologist, pharmacologistsand public health faculty are encouraged to apply for Catalyzer awards which are in the range of $25,000 for aone-year project. With this POCTRN supplement, we will ""plus-up"" these awards to a maximum of $100,000each to increase the scope and pace of the development. Applications are being accepted on a rolling basis,and funding decisions are made within 7 days. These two approaches will rapidly accelerate the developmentof promising COVID-19 technologies both in the US and globally.",2020,2021,NORTHWESTERN UNIVERSITY,6707769,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00962,3U54HL143541-02S1,Center for Advancing Point of Care Technologies (CAPCaT) Administrative Supplement,"RESEARCH SUMMARY/ABSTRACTThe goal of this initiative is to fast-track the implementation of carefully selected CAPCaT-supportedprojects that can help address the urgent healthcare issues created by the COVID-19 pandemic. Theextent and urgency of the situation requires an aggressive approach to accelerate the delivery of solutions toaddress the immediate needs. The proposed approach augments the strong technical, clinical andcommercialization expertise of CAPCaT to get needed solutions into practice within weeks to months.The Center for Advancing Point of Care Technologies (CAPCaT) in Heart, Lung, Blood, and SleepDiseases is an offshoot of a highly successful medical product incubator, the Massachusetts Medical DeviceDevelopment Center (M2D2) at the University of Massachusetts Lowell and Medical School campuses. Thefounding goal of M2D2 was to accelerate the development of medical devices, combining the engineering andbusiness expertise of UMass Lowell (UML) with the clinical expertise of UMass Medical School (UMMS) inWorcester. Expanding upon the vision and success of M2D2, the goal of CAPCaT is to support projects to develop and optimize novel point of care technologies (POCT) to improve the diagnosis and management ofheart, lung, blood, and sleep diseases. We have focused on these diseases because of the significantmorbidity, mortality, and cost associated with these diseases. Combined, these diseases account for 41% ofdeaths in the US and lead to over $400B in direct health care expenses plus lost income to affected patientsand caregivers. UMass has an established track record of clinical expertise and technology development in theHLBS diseases. CAPCaT funds projects that are in the later stages of POCT development, with a focus on theclinical validation of those devices. CAPCaT, along with M2D2, has a network of industry partners and fundersto support the development and commercialization of promising technologies. Among our industry partners areJohnson & Johnson, Boston Scientific, Amgen, and Hologic.CAPCaT is one of four Point of Care Technology Research Network (POCTRN) Centers (Emory/GA Tech,Northwestern, and Johns Hopkins University house the others). CAPCaT has worked with the other POCTRNCenters and its Coordinating Center (CIMIT-Mass General Hospital) and our scientific and program officers atNHLBI and NIBIB to review the situation and to understand unmet needs and resources accessible by thenetwork that can make a difference.",2020,2021,University of Massachusetts Chan Medical School,19278313,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00963,3UH4ES009759-28S2,IAFF Coronavirus and Infectious Disease Response Training,"The International Association of Fire Fighters (IAFF) proposes to continue its worker health and safety training programto train workers, across multiple disciplines, within a 150-mile radius of DOE weapons complex facilities in order toprevent work-related harm and improve worker-related health and safety. In alignment with the National Institute ofEnvironmental Health Sciences Worker Training Program's (WTP) strategic plan, the International Association of FireFighters (IAFF) seeks to conduct worker-based training to prevent and reduce exposure of emergency first responders andother workers who are at risk of exposure to Coronavirus through their work duties. This proposal includes a series ofinstructional train-the-trainer (TtT) modules to foster awareness of changes in the use of personal protective equipment forfire fighters, EMTs and paramedics, to mitigate the COVID-19 pandemic and to protect the health of those front-lineproviders while serving the public. The modules will support the 32-hour course designed and integrated in onlinewebinars, virtual classrooms and formal classroom use and follow the standard process in collaboration with NIEHS.Through this continued cooperative agreement, the IAFF will: 1. Ensure our Nation's first responders and other workers who are at risk of exposure to Coronavirus through their work duties are protected and available to respond to emergencies. 2. Using an evidence-based Train-the-Trainer curriculum that addresses the science of Coronavirus (clinical symptoms, mode of transmission, persistence in the environment, and treatment); infection control and worker protection (isolation/quarantine and PPE); working in the contaminated environment (sampling and decontamination); and behavioral health resiliency, exposures to COVID-19 will be reduced, first responders and other at risk workers will be able to be better prepared.",2020,2020,INTERNATIONAL ASSOCIATION FIRE FIGHTERS,200000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2020 +C00964,3UM1AI068636-14S1,"Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/","Project SummaryA novel pneumonia caused by a previously unknown betacoronavirus emerged in Wuhan, China, in December2019. The virus is closely related to the severe acute respiratory syndrome coronavirus (SARS CoV-1), whichled to an outbreak in 2003, and has been named SARS-CoV-2. The human disease caused by SARS-CoV-2 iscalled COVID-19.During the current SARS-CoV-2 outbreak, the incidence of known cases has rapidly increased such that, onJanuary 5, 2020, there were 59 confirmed cases, 278 cases on January 20, 2118 cases on January 26, andmore than 80,000 cases and 2700 deaths as of February 25, 2020, according to various international healthreporting agencies. As a result, on January 30, 2020, the International Health Regulations EmergencyCommittee of the World Health Organization (WHO) declared the COVID-19 outbreak a Public HealthEmergency of International Concern. On January 31, 2020, the US Department of Health and Human Servicesdeclared a public health emergency in the United States. As of March 21, 2020, there are 297,090 cases ofCOVID-19, including 22,177 cases in the United States (US), resulting in a total of 12,755 deaths globally.Despite quarantine measures, SARS-CoV-2 continues to spread (1). Outbreak forecasting and modelingsuggest that these numbers will continue to rise (2).At present, there is no specific antiviral therapy for COVID-19. Few treatment studies have been conductedbecause most human CoV strains cause self-limited disease, and care is supportive. After SARS-CoV-1 wasidentified in 2002-2003 and caused a large global outbreak, there was an increased interest in thedevelopment of specific therapeutic agents. SARS-CoV-1 patients were treated with corticosteroids, type 1 IFNagents, convalescent plasma, ribavirin, and lopinavir or ritonavir; except for ribavirin, many of these agentshave in vitro pre-clinical data that support their efficacy (3-11). Since the SARS-CoV-1 outbreak in 2002-2003,new therapeutic agents targeting viral entry proteins, proteases, polymerases, and methyltransferases havebeen tested; however, none of them has been shown to be efficacious in clinical trials (12-19).Given the lack of specific antiviral therapy for SARS-CoV-2 infection, and the known safety profiles and readyavailability of HCQ and Azithro as potential antiviral agents, based on pre-clinical and small clinical studies, thisrandomized, placebo-controlled trial will evaluate the efficacy and safety of HCQ and Azithro in persons whohave active SARS-CoV-2 infection and mild to moderate COVID-19 symptoms.",2020,2020,University of California-Los Angeles,9811257,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C00965,3UM1AI069424-14S1,UCLA AIDS Prevention and Treatment Clinical Trials Unit,"Project SummaryA novel pneumonia caused by a previously unknown betacoronavirus emerged in Wuhan, China, in December2019. The virus is closely related to the severe acute respiratory syndrome coronavirus (SARS CoV-1), whichled to an outbreak in 2003, and has been named SARS-CoV-2. The human disease caused by SARS-CoV-2 iscalled COVID-19.During the current SARS-CoV-2 outbreak, the incidence of known cases has rapidly increased such that, onJanuary 5, 2020, there were 59 confirmed cases, 278 cases on January 20, 2118 cases on January 26, andmore than 80,000 cases and 2700 deaths as of February 25, 2020, according to various international healthreporting agencies. As a result, on January 30, 2020, the International Health Regulations EmergencyCommittee of the World Health Organization (WHO) declared the COVID-19 outbreak a Public HealthEmergency of International Concern. On January 31, 2020, the US Department of Health and Human Servicesdeclared a public health emergency in the United States. As of March 21, 2020, there are 297,090 cases ofCOVID-19, including 22,177 cases in the United States (US), resulting in a total of 12,755 deaths globally.Despite quarantine measures, SARS-CoV-2 continues to spread (1). Outbreak forecasting and modeling suggestthat these numbers will continue to rise (2).At present, there is no specific antiviral therapy for COVID-19. Few treatment studies have been conductedbecause most human CoV strains cause self-limited disease, and care is supportive. After SARS-CoV-1 wasidentified in 2002-2003 and caused a large global outbreak, there was an increased interest in the developmentof specific therapeutic agents. SARS-CoV-1 patients were treated with corticosteroids, type 1 IFN agents,convalescent plasma, ribavirin, and lopinavir or ritonavir; except for ribavirin, many of these agents have in vitropre-clinical data that support their efficacy (3-11). Since the SARS-CoV-1 outbreak in 2002-2003, newtherapeutic agents targeting viral entry proteins, proteases, polymerases, and methyltransferases have beentested; however, none of them has been shown to be efficacious in clinical trials (12-19). Recent press-releaseand non-peer reviewed information suggests potential efficacy for a subset of SARS-CoV-2 patients, but thisremains to be reviewed and presented in peer-reviewed formats with sufficient granularity to be clinicallyimpactful.Given the continued spread of and lack of specific antiviral therapy for SARS-CoV-2 infection, this project willsupport additional testing and research to identify persons with SARS-CoV-2, and support infrastructure toincrease testing and conduct research on SARS-CoV-2 therapeutics and prevention in a safe and innovativeenvironment.",2020,2020,University of California-Los Angeles,300001,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics,2020 +C00966,3UM1AI069439-15S1,Vanderbilt CTU SARS-CoV-2 Supplement,"Project SummaryCoronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus2 (SARS CoV-2) required a rapid, coordinated response. The pandemic has interfered with many other importantendeavors, including NIH-sponsored non-COVID HIV clinical trials. We need robust plans to implementmeasures to expand SARS CoV-2, allowing research units to resume studies being conducted on HIV, whilemaintaining the safety and well-being of participants and staff. To this end, we have developed strategies relyingon a combination of testing for active disease, evaluating seroprevalence, and conducting operations in waysthat enforce social distancing and utilization of personal protective equipment (PPE). This project is beingimplemented at the Vanderbilt Therapeutics Clinical Research Site (VT-CRS), and the Washington UniversityPrevention & Therapeutics (WPT) CRS. This strategy will comprise two aims that involve research participants,their household contacts, and staff: Aim 1) To utilize resources obtained through this administrative supplementto expand SARS-CoV-2 testing within the regions of our Clinical Research Sites; and Aim 2) To utilize resourcesobtained through this administrative supplement to more quickly and fully resume on-site research activities atour Clinical Research Sites. Among the activities to be implemented are universal testing of study participantsfor infection by CoV-2 PCR prior to study visits, either by staff during parking lot drive-through visits or self-collected remotely by study participants. At one CRS, testing will also be offered to adult household contacts ofstudy participants. There will be active screening for symptoms of COVID-19. There will be CoV-2 antibodytesting at the beginning and end of the project period, of staff and/or study participants. This project willsubstantially expanding CoV-2 testing, and expedite the opening of our NIAID-funded CRSs. In addition, theexperience and information gained during this project will inform future strategies to further expand testing andfacilitate clinical trials operations.",2020,2020,Vanderbilt University Medical Center,558406,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2020 +C00967,3UM1AI069501-14S1,Case Clinical Trials Unit: Administrative Supplement NOSI AI-20-031.,"The primary objective of this supplemental application is to rapidly enhance the ability of the twodomestic CRSs in the Case Clinical Trials Unit to enroll and follow participants in COVID-19 preventionand treatment trials, with a particular emphasis on enhancing the sites' capacity to collect, process,store, and ship longitudinal biological specimens from these participants at any stage of the diseaseprocess. The following specific aims are proposed to accomplish this objective:Specific aim 1: To expand CRS capacity to identify new SARS-CoV-2 infections and to offer participationin clinical trials and observational studies. A key element to contribute meaningfully to prevention andtreatment trials will be to have access to recently diagnosed persons with SARS-CoV-2 infection who canbe offered participation. Here, we will enhance the capacity of the two CRSs to access these potentialparticipants by establishing partnerships with central laboratory leadership and expanding support forresearch staff who can support expanded testing and offer participation in research early after diagnosis.Specific aim 2: To improve CRS infrastructure to facilitate specimen collection and longitudinal follow-up of SARS-CoV-2 infected study participants. Among the challenges to refashion the CRSs to conductCOVID-19 trials are limitations in access to secure facilities and personal protection equipment. To addressthis, dedicated protective enclosures will be established at the Case CRS, and dedicated PPE will beacquired where needed for the duration of this funding period, which will be the critical interval duringwhich supply bottlenecks are anticipated to persist.Specific aim 3: To enhance participation of at-risk and SARS-CoV-2-infected persons in clinical researchprotocols. Recruitment of at-risk and infected participants into COVID-19 trials will require novelstrategies to reach out into the community, and to engage potential participants into clinical researchdespite no existing connection to the CRSs. To overcome these obstacles, we will devote dedicated effortfrom outreach coordinators specifically to COVID-19 recruitment, and establish online advertisementcampaigns to maximize opportunities for enrollment.Specific aim 4: To increase CRS capacity for processing and storage of biological specimens from COVID-19 research participants. The final barrier to processing, storing, and archiving specimens from COVID-19prevention and treatment clinical trials is the need for enhanced biosafety precautions in the processinglaboratory. At both CRSs, enhanced BSL-2 workstations will be established, with dedicated equipmentwhen needed, to increase the ability to process efficiently specimens derived from COVID-19 trials.",2020,2020,CASE WESTERN RESERVE UNIVERSITY,601237,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C00968,3UM1AI069503-14S1,COVID Supplement to Terry Beirn CPCRA Clinical Trials Unit,"CPCRA CTU # 60407: Admin Supplement NOT-AI-20-031 & PA-18-591 Principal Investigator: KAN, Virginia L.PROJECT SUMMARY/ABSTRACTThe Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) Clinical Trials Unit (CTU)# 60407 is pleased to submit an Administrative Supplement application in response to NOT-AI-20-031 and PA-18-591 through the George Washington University (GWU), the applicant organization, in collaboration with twoaffiliated Clinical Research Sites (CRSs). This CTU is led by Virginia L. Kan, MD, Principal Investigator.This supplement will provide funding to expand SARS-CoV-2 testing at the following two CTU-affiliated ClinicalResearch Sites:Site 01: George Washington University (GWU) CRS # 31608, Washington, DCSite 02: Houston AIDS Research Team (HART) CRS # 31473, Houston, TX",2020,2020,GEORGE WASHINGTON UNIVERSITY,601947,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2020 +C00969,3UM1AI106716-08S1,Breast Milk and COVID-19,"Project DescriptionIn less than 6 months, SARS-CoV-2, the virus that causes COVID-19, has spread across the globeindiscriminately infecting persons regardless of social status or age. Pregnant women and children are notspared but in contrast to other respiratory viruses, SARS-CoV-2 infection does not appear to be more severe inthese groups. Nevertheless, there is considerable concern about transmission from mother to infant particularlyvia breast feeding. Many viral infections such as HIV, CMV, and Ebola are transmitted through breast milk.SARS-CoV-2 enters human cells using the ACE 2 receptor which is present in breast tissue. This increasesconcern that the virus may be present in the breast milk of infected women. Although most children doremarkably well with infection, children <1 year of age have more severe illness with high rates ofhospitalization and admission to the intensive care unit. Therefore, defining the risks of SARS-CoV-2 breastmilk transmission is of critical importance. However, breast milk is not only a potential vector of transmissionbut can be a vehicle of protection by the transfer of protective antibodies and other immune factors. Bothhumoral and cellular immune responses in milk, including milk antibodies to respiratory viruses such asinfluenza, modulate infant disease. In fact, infants less than 6 months of age rely on maternal antibodies toprotect them against influenza and other respiratory viruses. Maternal flu immunization protects infants for atleast 6 months not only against influenza but other febrile illnesses. Whether breast milk contains antibodies toSARS-CoV-2 and whether it modulates the risk of infection to the infant is unknown. Answering thesequestions will require assays to detect the virus and its immune response in milk. We propose to fill thesecritical gaps by validating a quantitative RT-PCR assay for detecting SARS-CoV-2 in breast milk and thentesting over 100 milk samples from women infected with COVID-19. We will also test heat inactivationprotocols used by breast milk banks to verify that Holder pasteurization destroys SARS-CoV-2. At present,breast milk banks will not accept donations from women who have had COVID-19. As the infection spreadsthis exclusion will limit the availability to sick and vulnerable infants. Finally, we will develop an assay to detectantibodies to SARS-CoV-2 expressed in breast milk and compare those to the antibodies present in maternalblood. Information about maternal transfer of SARS-CoV-2 specific antibodies to the infant is a high priority toinform both breastfeeding practices and SARS-CoV-2 vaccination strategies.",2020,2020,University of California-Los Angeles,292406,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control",Diagnostics | Disease transmission dynamics,2020 +C00970,3UM1AI114271-06S1,Human epidemiology and response to SARS-CoV-2 (HEROS),"PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591 Supplement on Grant Number: 5UM1AI114271-06COVID-19 SURVEILLANCE STUDYSARS-CoV-2 causes severe respiratory disease seen predominantly in adults (COVID-19), but there is littleinformation regarding the infection burden in children. This is complicated by the observation that manyvirologically-confirmed cases in children are asymptomatic. Undocumented, and likely infectious, cases couldresult in exposure to a far greater proportion of the community than would otherwise occur. Indeed, it has beenproposed that undocumented (or silent) infections are the source for almost 80% of documented infections (Liet al, Science); thus, it is critical to determine the silent and symptomatic infection rate in children.To overcome challenges for clinical study implementation imposed by current healthcare access restrictions,we propose a surveillance study to determine the prevalence of SARS-CoV-2 infection (detection of virus innasal secretions) over time in children and their household contacts (caregivers and siblings). In addition to theneed for surveying children for asymptomatic SARS-CoV-2 infection, this study will allow a comparisonbetween children with asthma and other atopic conditions and children without those conditions.Figure 3.1 Study OverviewStudy designWe propose to conduct a prospective surveillance study in which children (index child) and their householdcontacts, including caregiver(s) and siblings, will be enrolled at study sites with NIH-funded studies. Potentialparticipants are those enrolled in existing NIH-funded studies (including the Wisconsin Infant Cohort Study, theChildhood Origins of Asthma [COAST] study, the MUPPITS-2 study, the RACR study and the UrbanEnvironment and Childhood Asthma[URECA] study). The intent is to recruit children who have asthma and/or other atopic conditions, as well ashealthy children, with extensive medical information and information on atopic status available as part of theirparticipation in cohort studies. The enrollment goal is approximately 2000 families to be enrolled overapproximately 2 weeks, and each participant will be observed for 6 months. During the study, biologicalsamples will be collected by the family at pre-determined intervals and symptom and exposure surveys will becompleted on-line at the time the biological samples are collected (Figure 1 Study Overview). Some biologicalsamples (nasal swabs and stool) will be collected by the caregiver at home. Blood samples will be collected ata home study visit or at an independent clinical laboratory, depending on feasibility. Samples will be processedin central laboratories, and Rho Inc. will serve as the coordinating center for the study.The primary outcome of the study will be the percent of index children and their household contacts withdetectable SARS-CoV-2 in nasal secretions. Secondary and exploratory outcomes are as described in thestudy protocol. PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591Supplement on Grant Number: 5UM1AI114271-06Project Summary (Primary award-ICAC)The overall goals of our proposal are designed to address current high priority unmetneeds in asthma that exist in inner cities, as well as elsewhere, including efforts to applyimmune-based strategies to reduce severity, diminish progression of disease, and teststrategies to prevent asthma. In that context, we hypothesize that environmental exposure toallergens, particularly cockroach, is a major risk factor for allergic sensitization and thedevelopment of asthma, and an important determinant of disease progression plus a target forimmunotherapy, severity and responsiveness to treatment. Moreover, we hypothesize thatIgE-sensitization, IgE-mediated processes, and wheezing with respiratory infections areimportant and linked risk factors in the development of asthma, and by targeting treatment toregulate IgE early in life it may be possible to prevent the progression from recurrent wheezingto asthma. Furthermore, asthma in inner-city children is represented by multiple phenotypes,some of which have uncontrolled disease which will benefit by treatment directed towardsphenotypic characteristics of their disease, e.g. exacerbation prone and obesity. Listed beloware our proposals to reach our goals and reduce unmet needs of asthma in the inner city.1. Aim 1. URECA, Urban Environment and Childhood Asthma is our inner-city birth cohort thatwas designed to establish the role and contribution of environmental risk factors on immunedevelopment and function that lead to asthma which will be further accomplished by studyingthe children until they are 14 to 16 years of age, and by this approach determine asthmaphenotypes and progression of disease.2. Aim 2. The Influence of the Inner City House Dust Microbiome and Respiratory andGastrointestinal Microbiome Composition Function and their Relationships to AllergicOutcomes. The overall aim of this mechanistic study is to determine whether the householdenvironment represents a significant source of bacteria that (1) populates respiratory and/orgastrointestinal microbiomes in early infancy; (2) to identify the key microbial species andfunction in both of these host niches that are associated with protection from asthma; (3) toidentify the microbial metabolic products and their function to shape immune responses; and (4)to pursue the development of protectivemicrobes as a treatment intervention to prevent asthma.3. Aim 3. Systems Biology Analysis in URECA. The overall aim of this mechanistic study is toextend the current ICAC2 epigenetic study to the application of a systems biology analysis tomore fully establish the complex integration of in utero and post-natal environmental stimuli,inherited factors, and dynamic biological responses in early childhood that predispose childrenin the inner city towards a Th2 phenotype and place them at risk for the development of asthma.4. Aim 4. The Immunobiology of Cockroach Sensitization - The Role of T Cells in Disease andImmunotherapy is a mechanistic study designed to test the hypothesis that different T-cellresponses to epitopes from aeroallergens, in this case cockroach, are important in thedevelopment of allergic airway disease and to determine their roles in immunomodulation byimmunotherapy. The proposed work will involve extensive collaboration with Aims 1 and 6.5. Aim 5. Preventing Progression to Asthma in Pre-School Aged Inner City Children (PAPI). Thisprotocol is aimed at the prevention of progression from recurrent wheezing to asthma and willaddress the hypothesis that treatment of high-risk inner-city children with allergic sensitizationand recurrent wheeze with omalizumab, an intervention directed towards IgE, will alter diseaseprogression as reflected by a reduced prevalence of asthma 2 years after the completion ofomalizumab therapy.6. Aim 6. Cockroach (CR) Immunotherapy (IT) in Inner-City Asthma: Effects on Disease Activityand Progression. The primary objective of this protocol is to determine whether the addition ofcockroach (CR) subcutaneous immunotherapy (IT) to standard, guideline-directed asthmamanagement is superior to standard asthma care alone in the treatment of persistent asthma in PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591 Supplement on Grant Number: 5UM1AI114271-06young inner-city children. Furthermore, by focusing on younger children, we will also test a keysecondary hypothesis as to whether the addition of CR IT will lead to a long-term reduction inasthma severity and persistence.7. Aim 7. Asthma Phenotype Informed Protocol (APIP). This protocol is designed to determine ifthe addition of mepolizumab, anti-IL-5, to treatment of children with difficult-to-control asthmaand peripheral blood eosinophilia (>300 cells/mm3) will prevent exacerbations, improve diseasecontrol, and potentially prevent progression of disease.8. Aim 8. The Use of Long-acting Anti-Muscarinic Antagonist (LAMA) Therapy in an Asthma andObesity Phenotype in Inner-City Asthma. This protocol is designed to test the hypothesis thatasthmatic children/adolescents with a BMI >85th percentile have enhanced parasympatheticairway tone, which is related to higher plasma leptin concentration and, as a consequence, willhave a greater response to anticholinergic treatment than asthma patients with lower BMIs.",2020,2021,UNIVERSITY OF WISCONSIN-MADISON,355680,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C00971,3UM1AI151958-01S1,Experimental and Computational Analysis of the Human Epidemiology and Response to SARS-CoV-2 (HEROS) Cohort,"PROJECT SUMMARYAtopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. AD isassociated with defective skin barrier function, microbial and viral dysbiosis, as well as various cutaneousimmune abnormalities including type 2 inflammation and decreased cutaneous host defense. The AtopicDermatitis Research Network-Leadership Center (ADRN-LC) provides that scientific strategy andorganizational structure to elucidate mechanisms of skin barrier dysfunction, cutaneous immune responses,and viral determinants of atopic dermatitis (AD). An emerging virus with potential direct implications to ADand other allergic diseases is SARS-CoV-2. SARS-CoV-2 is the virus which causes COVID-19 illnesses,which are rapidly affecting humans around the globe. While initial epidemiological data have focused on casesthat resulted in severe respiratory disease seen predominantly in adults, little information regarding the infectionburden in children is available. This is complicated by the observation that many children experienceasymptomatic infections. Undocumented, and likely infectious, cases could result in exposure to a far greaterproportion of the community than would otherwise occur. Indeed, it has been proposed that undocumented (orsilent) infections are the source for almost 80% of documented infections; thus, it is critical to determine thesilent and symptomatic infection rate in children and to understand why they develop less severe orasymptomatic disease. To overcome challenges for clinical study implementation imposed by currenthealthcare access restrictions, this surveillance study will enroll and prospectively observe eligible children thatare current participants in NIH-funded pediatric research studies and their family members. We will collect nasalswabs from all subjects in 2 week intervals for a 4 month period, again at 6 months, and during respiratoryillnesses. Our group will act as the laboratory processing and analysis site for the study. We will extractDNA/RNA from all swabs and perform a qPCR assay test for the SARS-Cov-2 virus. This will allow us todetermine the incidence of the SARS-Cov-2 in the U.S. population and how it varies between children andadults, and those with asthma and other lung diseases. Secondly, we will perform Dual RNA-seq on RNA fromnasal swabs to determine the host epithelial and immune cell response to infection with SARS-Cov-2 andCOVID-19 respiratory illnesses. This data will also allow us to identify different strains of the SARS-Cov-2 viruscirculating in the U.S., their geographical distribution, and how these strains relate to COVID-19 illness severity.",2020,2021,NATIONAL JEWISH HEALTH,2282196,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity",2020 +C00972,3UM2AI117870-06S1,"Rho Federal Systems Division, Inc. NIAID DAIT SACCC","PROJECT SUMMARY / ABSTRACT COVID-19, the infectious disease caused by SARS-CoV-2, is rapidly affecting humans around the globe.While initial epidemiological data have focused on cases that resulted in severe respiratory disease seenpredominantly in adults, little information regarding the infection burden in children is available. This iscomplicated by the observation that many virologically confirmed cases in children are asymptomatic (Dong etal, Pediatrics, PMID 32179660). Undocumented, and likely infectious, cases could result in exposure to a fargreater proportion of the community than would otherwise occur. Indeed, it has been proposed thatundocumented (or silent) infections are the source for almost 80% of documented infections (Li et al, Science,PMID 32179701); thus, it is critical to determine the silent and symptomatic infection rate in children. The purpose of this project is to develop, implement, and report on a surveillance study that will enroll andprospectively observe eligible children who are current participants in NIH/NIAID/DAIT-funded pediatricresearch studies and their family members. Many of these studies are focused on populations of children withasthma or other atopic conditions. The primary objective of this study will be to determine the incidence ofSARS-CoV-2 infection (detection of virus in nasal secretions and stool and antibodies to the virus in blood)over time in children and their household contacts (caregivers and siblings).",2020,2021,"RHO FEDERAL SYSTEMS DIVISION, INC.",10601507,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2020 +C00973,5DP1GM133052-02,High-throughput single-molecule protein identification via super-resolution imaging,"Modified Project Summary/Abstract SectionA technology capable of generating robust protein data across various biological states, with the sensitivity and coverage available to next-generation sequencing, would drastically change our understanding of cellular proteomes and ability to detect rare proteins in limited samples. Mass spectrometry is a powerful tool for proteomics. However, it suffers from limited sensitivity (>10{6} molecules required) preventing the identification of low-abundance proteins and single-cellproteomics. A high-throughput single-molecule protein identification method remains a key technical challenge for the proteomic community. Addressing this challenge will dramatically improve the ability to discover and assay novel biomarkers, with transformative impact in our understanding of cancer, immunology and brain research. We propose a robust high-throughput strategy for single-molecule protein identification. This approach will be based on our recent technological breakthrough on developing the highly multiplexed (10-plex; Nature Methods 2014), precisely quantitative(>90% precision and accuracy; Nature Methods 2016), and ultra-high resolution (sub-5 nm; Nature Nanotechnology 2016) DNA-PAINT super-resolution imaging method. Using DNA-PAINT to image a DNA-barcoded and stretched protein will provide a unique optical signature for accurate identification of any proteins in a complex mixture. This method will enable parallel identification of proteins with single-molecule sensitivity, resulting in broadly transformative impacts on fundamental and translational biomedical studies. To address the unmet testing need for the current COVID-19 pandemic, we will also work to develop a rapid diagnostics device.",2021,2023,HARVARD UNIVERSITY,1319500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2018 +C00975,5K01TW010279-05,Epidemiology of zoonotic viruses in forest communities in a key biodiversity area of rural Myanmar," DESCRIPTION (provided by applicant): The majority of emerging infectious diseases originate in wildlife reservoirs and this is especially important in countries where human / wildlie contact is prevalent and disease diagnostics are limited. The risk for zoonotic viral disease presence and emergence increases in geographic areas with higher mammal diversity and ecosystem disruption. This makes Southeast Asia a hotspot for endemic and emerging zoonotic viruses, including those with pandemic potential such as SARS-associated coronavirus and influenza H5N1, as well as those causing regional outbreaks such as Nipah virus and Japanese encephalitis. Myanmar is hypothesized to be a key area for zoonotic viral emergence because its geography encompasses eight unique biodiversity areas that are rich in mammal and avian fauna and because it has recently undergone significant landscape changes through land conversion for agriculture and timber harvesting. Little is known about the types of zoonotic viruses circulating in rural forest communities and the human behaviors associated with wildlife contact that could be contributing to disease burdens. This International Research Scientist Career Development Award (K01) will provide Dr. Tierra Smiley Evans, a Post-doctoral DVM and infectious disease epidemiologist at the University of California Davis, the protected time to investigate zoonotic viral sharing between humans and wildlife within high-risk forest communities in a key biodiversity area of Myanmar. Molecular, serological and behavioral epidemiological approaches will be used to (1) investigate zoonotic virus spillover between wildlife and humans in a key biodiversity corridor and (2) identify key demographic, behavioral, geographic and species contact risk factors for zoonotic viruses in forest communities. The proposed K01 research, mentorship and training will provide Dr. Evans with the opportunity to expand her skills in (1) advanced epidemiological study design to investigate viral transmission dynamics between humans and animals, (2) advanced pathogen discovery including next-generation molecular and serological techniques, (3) applied behavioral epidemiology in an international field setting and (4) incorporating local partners and building lasting scientific collaborations which are essential to successful international research. Dr. Evans will engage in a five-year training program under the primary mentorship of the University of California Davis One Health Institute and Center for Comparative Medicine, the Department of Medical Research (Lower Myanmar) Virology Research Division, and the Center for Infection and Immunity at Columbia University.",2020,2021,UNIVERSITY OF CALIFORNIA AT DAVIS,144585,Animals | Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas | South-East Asia,,,,United States of America,United States of America | Myanmar,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2016 +C00977,5P01AI060699-13,Project 3,"Project Summary/AbstractMiddle East Respiratory Syndrome (MERS) was recognized as a significant illness onthe Saudi Arabian peninsula in mid-2012, and the causative agent was rapidly identifiedas a novel coronavirus (CoV), termed MERS-CoV. MERS has a high mortality (~35%),associated with severe lung disease. Similar to the SARS virus that caused an epidemicin 2003-4, there is ongoing global concern due to MERS high fatality rate. To date,cases of MERS have been reported in 26 countries. Dipeptidyl peptidase 4 (DPP4,CD26) is the receptor for MERS-CoV. Epidemiologic studies have established thatMERS is zoonotic in origin, with evidence for a closely related virus in dromedary camelson the Arabian peninsula and throughout Africa. Spread from camels to people isdocumented, as well as person-to-person spread among health care workers in hospitalsettings. A lack of autopsy studies from MERS fatalities has hindered understanding ofMERS-CoV pathogenesis. Thus, MERS is the most recent confirmation thatcoronaviruses can jump from their animal hosts, infect humans, and cause severedisease of global significance. There is a pressing need to better understand MERSdisease pathogenesis and to develop vaccines and therapies. There are 3 specific aims.Aim 1. To understand how an in vivo evolved MERS-CoV causes lethal lungdisease. We developed mice that have the human receptor for MERS-CoV. Using theseanimals we developed a mouse-adapted virus that causes significant lung disease.These studies will advance our knowledge of the causes of MERS-related lung disease.Aim 2. To investigate how adaptive mutations in MERS-CoV contribute toincreased virulence. We sequenced the mouse-adapted virus strains and assembledtheir genomes. We will use this genetic information to investigate relationships betweenthe virus gene products and the host responses that lead to severe lung disease.Aim 3. To investigate how DPP4 abundance and function influence MERS diseasepathogenesis. DPP4 has enzymatic activity that cleaves two amino acids off of targetprotein substrates, thereby changing protein functions. DPP4 abundance and enzymaticactivity may contribute to disease. These experiments will advance our knowledge ofhow DPP4 activities may underlie to disease outcomes.",2021,-99,UNIVERSITY OF IOWA,340075,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis", +C00978,5P01AI060699-13,Administrative Core,"ABSTRACTThe Administrative Core will coordinate the activities of the Projects and the Animal/VirologyCore. It will be responsible for encouraging the exploration of new research directions and forarranging consultations with the Internal and External Advisory Committees. It will beresponsible for preparing scientific progress reports and renewal applications. It will organizethe monthly meetings of the Projects at which research progress is presented. It will beresponsible for budget allocation and for monitoring expenses. It will allocate travel funds. Twoof the projects of the PPG are located offsite, in Chicago and in Madrid, Spain. Thus, importantfunctions of the Administrative Core will be to facilitate discussions between the Projects byarranging videoconferences between the Iowa, Loyola and Madrid projects and to coordinatetwo meetings per year at the University of Iowa of all of the Project Directors. In summary, theAdministrative Core will have a critical role in making sure that the PPG is efficiently organizedand is productive as possible.",2021,-99,UNIVERSITY OF IOWA,88799,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,, +C00979,5P01AI060699-13,Animal/Virology Core,"ABSTRACTThe Animal/Virology Core Laboratory is directed by a senior, experienced postdoctoral fellow,Dr. Rudragouda Channappanavar, under the guidance of the Core Director, Dr. Perlman. TheCore will be primarily based in a University of Iowa BSL3 laboratory that is equipped for tissueculture and animal work. Personnel working in the Core are experienced in virological and cellculture techniques and in handling, infecting and analyzing mice. The Animal/Virology Core hasseveral functions that are critical for success of this PO1 grant. 1. It will maintain colonies ofhDPP4-knock-in mice. 2. It will propagate and titer nonrecombinant and recombinant mouse-adapted and human strains of MERS-CoV and SARS-CoV and will infect mice with theseviruses. 3. It will monitor mice for clinical disease and weight loss and will harvest tissue. 4. TheCore will prepare samples for histological and immunohistochemical analysis and will prepareRNA and protein from infected tissue. 5.The Core will analyze mice for virus-specific antibodyand T cell responses. 6. The Core will develop recombinant MERS-CoV and SARS-CoV usingBAC DNA clones prepared by the individual projects. The Core will also be responsible forensuring that protocols for working with animals and for working under BSL3 laboratoryconditions are up-to-date. While the Core will teach members of the Project methods importantfor analysis of mice under BSL3 conditions, it will primarily be responsible for performing most ofthese analyses. The Core will provide reagents and perform common assays efficiently, therebystandardizing results and enhancing synergistic interactions. Additionally, all projects willinteract with the Core, thereby facilitating interactions between members of the PPG. Byproviding these services, the Core will allow Program investigators to focus on issues related toMERS and SARS pathogenesis and to the development of anti-viral therapies and vaccines.",2021,-99,UNIVERSITY OF IOWA,296782,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis", +C00980,5P01AI060699-13,Project 1,"Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) arecoronavirus-induced human respiratory diseases with high case-fatality rates. Disease is especiallysevere in aged populations. In the previous funding period, we showed that age-dependent increasesin prostaglandin D2 (PGD2) and an upstream phospholipase A2, PLA2G2D contributed to poorimmune responses and decreased survival. The lung is in a state of chronic inflammation, resultingfrom continued exposure to environmental antigens. We postulated that PLA2G2D, which has anti-inflammatory properties, is upregulated to counter this low grade inflammation, resulting in delayedresponses to innocuous antigens but also to rapidly replicating viruses like MERS-CoV and SARS-CoV. In contrast, genetic absence of DP1, the PGD2 receptor on myeloid cells, appears to result inpoor respiratory dendritic cell activation suggesting that PGD2-DP1 signaling may have pro-inflammatory properties at early times after infection. Our central hypothesis is that small lipidmediators are major factors in the inflammatory milieu in the lung, affecting many aspects of theimmune response to MERS-CoV, SARS-CoV and other respiratory pathogens. This hypothesis will beapproached in the following specific aims: 1. To determine the mechanism of PLA2G2D upregulationand the role of PLA2G2D in vaccine responses in 12m old mice. CoV replication includes extensivecellular membrane rearrangements. The role between these rearrangements, the induction of oxidativestress and the upregulation of PLA2G2D will be investigated. 2. To determine the role of PGD2-DP1signaling in the immune response to SARS-CoV in 12 m mice. The absence of PGD2-DP1 signalingresults in diminished rDC activation and type I IFN (IFN-I) expression and increased inflammasomeactivation. Our goal is to determine whether changes in inflammasome activation are the majorpathogenic effect of absent PGD2-DP1 signaling or if other factors are also involved. 3. To determinewhether disease severity in murine MERS is age-dependent and whether PGD2 and PLA2G2Dcontribute to poorer outcomes. Using our newly developed hDPP4-KI mice and mouse-adaptedMERS-CoV, we will determine whether MERS-CoV in mice also causes an age-dependent disease.We will also assess whether changes in eicosanoid expression contribute to more severe disease.MERS-CoV, unlike SARS-CoV, productively infects macrophages. In this aim we will determinewhether productive infection of human and murine macrophages modulates PLA2G2D expression.",2021,-99,UNIVERSITY OF IOWA,79983,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis", +C00981,5P01AI060699-13,Project 4,"SUMMARYTo prevent deadly CoV infections we propose to study the molecular basis of coronavirus-induced lung edema and its resolution, through the identification of (i) Signaling pathwaysresulting in severe lung disease to inform inhibitors as antiviral candidates; and (ii) Virusvirulence genes. Deletion of these genes will lead to attenuated vaccine candidates. Three aimsare proposed: Aim 1. To determine the factors involved in edema induction and resolutionduring CoV infection. We have shown that both E and 3a proteins of SARS-CoV, and proteins Eand 5 of MERS-CoV include two sequence domains involved in virulence, one containing a PDZbinding motif (PBM), and another one encoding ion channel (IC) activity. The binding of theSARS-CoV E protein PBM to proteins containing the PDZ motif causes Acute RespiratoryDisease Syndrome in infected animals. The importance of the PBM is likely associated with itsability to bind to more than 400 cellular proteins and, therefore, to regulate many cell signalingpathways. We will study the whole-proteome interactions between PBMs in MERS-CoV, andcellular PDZs. This interactome will be the basis for the identification of peptides interfering withPBM-PDZ binding, using peptide libraries. The mechanism of inflammasome activation byMERS-CoV proteins with IC activity will be studied. Edema resolution is possible by twoenzymatic activities: epithelial sodium channel activity (ENa+C) and Na+/K+ ATPase that moveNa+ ions from the alveolar fluid into the interstitium promoting water elimination. We showedthat SARS-CoV E protein binds Na+/K+ ATPase and have postulated that this binding reducesNa+/K+ ATPase activity, leading to lung edema; this will be investigated in this project. Aim 2.We propose to identify viral and host non-coding RNAs involved in MERS-CoV pathogenesisand lung inflammation, as potential targets in antiviral and anti-edema strategies. Aim 3. Todevelop safe live-attenuated vaccines for MERS-CoV. The construction of MERS-CoVsdefective in propagation, and the generation of attenuated, dissemination competent rMERS-CoVs are proposed. Maximizing biosafety and genetic stability of the vaccine candidatesare main goals of the project.",2021,-99,UNIVERSITY OF IOWA,182399,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Pre-clinical studies", +C00982,5P01AI060699-13,PPG: SARS-CoV-host cell interactions and vaccine development,"OVERVIEW-SUMMARYThe emergence of the Severe Acute Respiratory Syndrome (SARS) in 2002-3 and the Middle EastRespiratory Syndrome (MERS) in 2012 demonstrates that zoonotic coronaviruses (CoV) have and willlikely continue to spread from zoonotic sources to infect Human populations. MERS-CoV continues tocirculate in camels and to spread to susceptible humans, highlighting the need to better understandthe pathogenesis of diseases mediated by pathogenic human respiratory CoV. In this PPG,investigators with experience in coronavirus pathogenesis, molecular biology, immunology andvaccinology will work together to understand how virus factors and dysregulated innate and adaptiveimmune responses contribute to MERS and SARS disease in young and aged animals and in animalswith co-morbidities. All of the projects will utilize newly developed mice expressing human MERSreceptor (DPP4) in lieu of the mouse receptor (hDPP4-KI) and a mouse-virulent MERS-CoV, selectedin these mice (MERSMA). Project 1 will use MERSMA to investigate the role of aging in infected mice.Project 1 is also based on published data showing that specific eiconsanoids with anti-inflammatoryproperites and their upstream phopholipases increase during aging, contributing to a delayed immuneresponse after SARS-CoV (and by extension, perhaps MERSMA) infection. Project 2 is based onpreliminary data showing that MERS-CoV has a greater dependence on host cell proteases for virusentry than does SARS-CoV. This project will investigate unique mutations found in the surface (S)glycoprotein of MERSMA that appear to affect protease function. Project 3 will investigate howMERSMA causes more severe disease than the initial human EMC/2012 strain, with focus on theORF4b accessory protein. This project will also investigate how hDPP4 contributes to diseaseseverity. Project 4 is based on published data showing that the CoV E protein has ion channel activity,is a virulence factor and contains a PDZ binding domain (PBM), which is critical for virus viability. Thisproject will focus on how the E protein causes edema in lungs and on the role of the PBM inpathogenesis. A novel PBM in the C terminal of E arose in MERSMA during mouse passage and itsrole will be studied. This project will also continue to develop safe, live attenuated MERS and SARSvaccines. All of the projects will use the Animal/Virology Core, which will provide nonrecombinant andrecombinant MERS-CoV and SARS-CoVs and will monitor and analyze infected mice. Using the Corefor these purposes will maximize experimental quality control and effective use of our resources.These projects are all interrelated and collaborative, will take advantage of the unique skills andexpertise of the project directors and provide new information about MERS and SARS pathogenesisthat is essential to vaccine development.",2021,2022,UNIVERSITY OF IOWA,1254329,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2004 +C00985,5R01AI089728-10,Receptor recognition and cell entry of coronaviruses,"Receptor recognition and cell entry by viruses are two initial and essential steps in viral infection cycles. They are important determinants of viral host ranges, tissue tropisms and pathogenesis, and are primary targets for human intervention. Coronaviruses (CoVs) pose serious health threats to humans and other animals. SARS-CoV and MERS-CoV have infected thousands of people with significant fatality, whereas porcine epidemic diarrhea CoV is currently causing ~100% fatality in piglets. A virus-surface spike protein guides CoV entry into host cells by binding to its host receptor via its S1 subunit and fusing viral and host membranes via its S2 subunit. S1 from different CoVs recognizes a variety of host receptors through one or both of its domains (S1-NTD and S1-CTD), and the S1/S2 boundary is cleaved by host proteases for activation of membrane fusion by S2. Our previous research has determined a number of crystal structures of CoV S1 domains by themselves or in complex with their respective receptor, and also shown how proteolysis regulates the cell entry of some CoVs. Our research has contributed critically to the current knowledge about the molecular mechanisms for CoV receptor recognition, cell entry, and cross-species transmission. In this competitive renewal of R01, we will continue to investigate how CoVs exploit host receptors and host proteases for cell entry. This proposal has three specific aims. Aim 1 examines receptor binding by CoV S1-NTDs. Specifically, we will investigate whether S1-NTDs from different CoV genera have the same structural fold and evolutionary origin as host galectins (galactose-binding lectins). We will also examine how CoV S1-NTDs recognize sugar receptors. These studies will reveal the evolutionary origins of CoV S1-NTDs, enhance understanding of sugar recognition by CoVs, and may facilitate future design of sugar analogues and subunit vaccines to inhibit CoV infections. Aim 2 focuses on receptor binding by CoV S1-CTDs. Specifically, we will analyze the interactions between the S1-CTDs of bat SARS-like CoVs (SL-CoVs) and the protein receptor homologues from humans and other animals, and elucidate how bat SL-CoVs transmitted to humans and other animals to cause the SARS epidemic through evolutionary changes in their S1-CTDs. These studies will provide critical information for understanding emergence potential of bat SL-CoVs and for facilitating epidemic monitoring and control. Aim 3 investigates cell entry by CoVs. Specifically, we will investigate what host proteases activate CoV entry and how the proteases motifs in CoV spikes have evolved to modulate CoV entry. These studies will reveal how host proteases regulate CoV entry to meet their specific need for host range, tissue tropism and pathogenesis, and may facilitate future design of protease inhibitors to block CoV entry. Overall, this proposal investigates the molecular and structural mechanisms for receptor recognition, cell entry, cross-species transmission, and tissue tropism of CoVs, which will lead to novel principles in virology. This research is also important for evaluating the emerging disease potentials of CoVs and for preventing, controlling and treating CoV infections in humans and other animals.",2020,2021,UNIVERSITY OF MINNESOTA,455796,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2010 +C00986,5R01AI108197-08,Determinants of Coronavirus Fidelity in Replication and Pathogenesis,"PROJECT SUMMARYViruses in the Coronaviridae family (CoVs) have emerged as zoonoses with pandemic potential twice in the21st century, causing severe human disease. Middle East respiratory syndrome (MERS)-CoV continues tocause new cases of lethal respiratory infections with 35% mortality. Further, severe acute respiratory syndrome(SARS)-like bat CoVs currently circulating are capable of infecting human cells, establishing the risk for futureemergence of zoonotic CoVs. There are no approved vaccines or antivirals for any human or zoonotic CoV,emphasizing the importance of identifying vulnerable and broadly conserved CoV targets for therapeuticintervention and vaccine development. Most RNA viruses generate genetic diversity required for interspeciesmovement and adaptation via error-prone RNA-dependent RNA polymerases (RdRps) that lack proofreading.In contrast, all CoVs encode a 3'-to-5' exoribonuclease (ExoN) in nonstructural protein 14 (nsp14-ExoN) that isa key driver of CoV evolution and adaptation via RNA-dependent RNA proofreading. During the four years offunding for this program, we have shown that CoV nsp14-ExoN mediates high-fidelity replication and that CoVslacking ExoN activity (ExoN(-)) are less fit during infection in cell culture, more sensitive to RNA mutagens, andattenuated in a murine model of SARS-CoV infection. Our findings suggest that divergent β-CoVs - MERS-CoV,SARS-CoV, and murine hepatitis virus (MHV) - have differential requirements for ExoN to sustain viability andoverall fitness. Finally, ExoN may play important and previously unpredicted functions in CoV resistance tohost innate immune surveillance. Thus, our published and preliminary studies support the scientific premisethat nsp14-ExoN is a master regulator of CoV fitness, evolution, and pathogenesis via functions in viralreplication, fidelity, and evasion of host innate immune responses. Specific aims of this proposal will define: 1)Sequence and structural determinants of nsp14-ExoN-mediated functions in CoV replication, fidelity, andinterferon sensitivity; 2) Adaptations in nsp14, nsp12-RdRp, and elsewhere in the CoV replicase thatcompensate for loss of ExoN-mediated fidelity; and 3) Mechanisms of ExoN regulation of the innate antiviralimmune response in vitro and in vivo. The availability of a high-resolution structure of nsp14; facile reversegenetics systems for MHV, SARS-CoV, and MERS-CoV; and robust, relevant animal models for SARS-CoVand MERS-CoV will allow us to address these questions, resulting in a comprehensive understanding of ExoNroles and mechanisms in CoV replication, adaptation, and pathogenesis. These studies will catalyzeapproaches targeting ExoN as a basis for stably attenuated CoV vaccines and novel antiviral drugs.",2020,2023,Vanderbilt University Medical Center,672084,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2013 +C00988,5R01AI125215-04,Targeting TLR Signaling Pathways to Blunt Pathogen-mediated Acute Lung Injury,"For decades, a ""one bug, one drug"" approach has characterized development of vaccines or treatments forspecific infectious diseases. We propose a different approach based on the development of novel treatment ofinfectious diseases by capitalizing on common host innate immune responses that are triggered during infection by influenza and other priority pathogens. Influenza virus infects up to 5 million people yearly worldwide,killing as many as ~500,000. Our strong experimental evidence demonstrates that the potent TLR4 antagonist,Eritoran (Eisai, Inc.), as well as multiple other TLR4 antagonists, significantly decreased both acute lung injury(ALI) and mortality when administered therapeutically to influenza-infected mice. Eritoran not only blocks influenza-mediated release of host-derived ""danger-associated molecular patterns"" (DAMPs), but also bluntedDAMP-mediated TLR4 signaling in macrophages that normally results in a ""cytokine storm."" While we haveelucidated several novel mechanisms by which influenza mediates ALI and lethality that are counteracted byEritoran therapy (e.g., release of host-derived DAMPS that signal through TLR4; increased tight-junction permeability leading to pulmonary edema; a role for IL-1α/β in lethality), our understanding of the overall innateimmune signaling pathways that control influenza-induced ALI and Eritoran-mediated protection remains incomplete, necessitating further investigation to develop a highly efficacious host-directed therapy. Therefore,Specific Aim 1 will focus on the identification of innate immune mechanisms that underlie both influenza sensitivity and Eritoran-mediated protection. We will take advantage of genetically modified mouse strains to dissectthe signaling pathways engaged. Whether TLR4 must be expressed on stromal and/or myeloid cells, the roleof virus-induced epithelial cell necroptosis in DAMP release, mechanisms by which non-TLR4 PRRs contributeto influenza resistance/susceptibility, and the possibility that TLR2/TLR4 dimerization is required for the hostresponse to influenza will be evaluated as novel potential mechanisms that can be exploited to enhance therapeutic efficacy. In Specific Aim 2, the therapeutic benefit of a novel IKKβ inhibitor, E6070 (Eisai, Inc.), againstinfluenza, alone or in the presence of current anti-influenza antiviral therapies, will be tested in cotton rats(CR), a second rodent species that permits analysis of ALI in response to infection by non-adapted human influenza isolates. Aim 2 will also compare Eritoran and E6070 in CR in a model of secondary staphylococcal(MRSA) pneumonia following influenza infection. Lastly, we will assess the relative effectiveness of Eritoranand E6070 for the ability to block ALI caused by other clinically important or biothreat pathogens associatedwith ALI in humans (e.g., Francisella tularensis, Streptococcus pneumoniae, Klebsiella pneumoniae, SARS-CoV and MERS-CoV), first in mice, and, if effective, in CR. These experiments will challenge the overarchingcentral hypothesis that TLR antagonists represent broad-based, therapeutic agents that mitigate pathologichost responses to multiple ALI-inducing priority pathogens.",2020,2022,UNIVERSITY OF MARYLAND BALTIMORE,533933,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2017 +C00989,5R01AI127521-04,"Structure, Function and Antigenicity of Coronavirus Spike Proteins","Coronaviruses have the largest genomes among known RNA viruses and are phylogenetically divided into fourgenera. Some betacoronaviruses, such as HKU1, circulate annually in humans and cause mild yet prevalentrespiratory disease whereas others, such as SARS-CoV and the recently emerged MERS-CoV, have causedpandemics with high case-fatality rates. Due to their pandemic potential and airborne transmissibility, highlypathogenic coronaviruses are now classified as NIAID Category C priority pathogens. Coronavirus cell tropismand host range are in large part determined by the viral surface spike (S) glycoprotein, which is the largestknown class I viral fusion protein. After binding to host receptors and activation by host proteases, the Sproteins undergo large conformational rearrangements that result in fusion of the viral and host-cellmembranes. A molecular understanding of the structure, function and antigenicity of intact, trimeric S proteinswould identify sites of vulnerability that could be targeted by vaccines, therapeutic antibodies and small-molecule antivirals. However, structural studies have been primarily limited to small S protein fragments, whichhas precluded a unifying structural framework for the biology of coronavirus S proteins. To address this knowledge gap, we have generated soluble, trimeric S proteins from HKU1 and MERS-CoV that are amenable to structural analysis by X-ray crystallography and cryo-electron microscopy. We willdetermine atomic-level structures of these S proteins in both the prefusion and postfusion conformations,which will identify commonalities and differences among divergent betacoronaviruses and define theconformational end-states of the fusion process (Aim 1). With these constructs and a range of biochemical andbiophysical assays, we will determine the molecular basis for receptor-induced conformational changes andinvestigate the effects of host proteases and acidification on this process (Aim 2). The combination of thesestudies will provide key molecular insights into S protein-mediated membrane fusion and answer long-standingquestions regarding S protein triggering. Similar to other class I fusion proteins, such as influenzahemagglutinin (HA) and HIV-1 envelope (Env), coronavirus S proteins are the primary target for neutralizingantibodies and are thus a critical component of developmental vaccines. Currently, the best-characterizedantibodies against coronaviruses target the receptor-binding domain (RBD) of the S protein and preventbinding to host cells. The RBD, however, is the most variable part of the spike protein and antibodies thattarget this domain are unlikely to be cross-reactive, similar to most HA head-binding antibodies. Therefore, wewill define the epitopes and mechanisms of antibody-mediated neutralization for novel, non-RBD-directedneutralizing antibodies isolated by our collaborator Dr. Barney Graham (Aim 3). By identifying conserved sitesof vulnerability, these studies will provide the foundation for the development of immunotherapies and vaccinesthat broadly protect against highly pathogenic betacoronaviruses, including those that have yet to emerge.",2020,2022,"UNIVERSITY OF TEXAS, AUSTIN",613032,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2017 +C00991,5R01AI129822-04,Investigating seasonal drivers of viral zoonoses from Madagascar fruit bats,"Zoonotic pathogens derived from an animal reservoir account for some 60-75% of emerginginfectious diseases in humans, a disproportionate number of which take place in resource poorcountries where the economic and social burden of corresponding health crises is greatest. Bats havereceived much attention in recent years for their role as the putative reservoir hosts for a number ofhigh profile, virulent zoonoses, including Ebola and Marbug filoviruses, Hendra and Nipahhenipaviruses, and SARS coronavirus, all of which demonstrate peaks in transmission-both betweenbats and from bats to spillover hosts (including humans)-during the resource-poor dry season for thesystem in question. Seasonal forcings are known to play an important role in driving epidemic cycles ininfectious diseases for both humans and wildlife, though the mechanistic drivers of seasonality cansometimes be difficult to identify. In bat systems, researchers have posited that dynamical patternscould result from pulsed additions of annual, synchronous births to the pool susceptible to immunizingviruses, while others have suggested that bats might instead maintain these viruses as persistentinfections across the duration of their lifespans and undergo periodic bouts of viral shedding. A trueunderstanding of these dynamics will be essential to predicting and preventing the next bat zoonosis, acritical public health aim for developing world countries, like Madagascar, where we base our work. Todate, longitudinal data of a fine enough scale do not exist to distinguish among the proposedhypotheses. Our project brings together a diverse team of molecular biologists from Institut Pasteur deMadagascar and Duke-NUS, epidemiological modelers from Princeton, and field ecologists fromHarvard to address these challenges. In Aim 1 of our research, we introduce novel Luminex assays toidentify henipaviruses, filoviruses, coronaviruses, and lyssaviruses antibodies in both bat and human serum samples in Madagascar.In Aim 2, we build mechanistic transmission models exploring the proposed hypotheses of seasonaldrivers of infection dynamics in bat systems, and in Aim 3, we unite these goals in a longitudinal model-guided field study, with corresponding serological and molecular analyses, which will generate the dataneeded to enable effective model comparison and evaluation. Our work addresses questions of criticalinterest to both evolutionary biology and public health, while simultaneously building scientificcapacities in the developing world.",2020,2022,PASTEUR INSTITUTE FROM MADAGASCAR,134977,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Filoviridae | Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Africa,Africa,,,,Madagascar,Madagascar,Animal and environmental research and research on diseases vectors | Epidemiological studies,Immunity | Animal source and routes of transmission | Disease surveillance & mapping,2017 +C00992,5R01AI130092-03,Small Molecule Protease Inhibitors against MERS-CoV,"PROJECT SUMMARYSince the unexpected emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2013, theongoing outbreaks of MERS in the Middle East and the potential for global transmission of MERS, exemplifiedby an outbreak in South Korea in 2015, have underscored the urgent need for effective preventive andtherapeutic measures against this highly virulent coronavirus. MERS-CoV expresses two polyproteins thatundergo proteolytic processing by two virus-encoded proteases, a 3C-like protease (3CLpro) and a papain-likeprotease, to generate functionally active proteins. MERS-CoV 3CLpro processes the majority of the cleavagesites on the polyproteins and is essential for viral replication, making it an attractive therapeutic target. A seriesof potent dipeptidyl inhibitors of the 3CLpro of coronaviruses including MERS-CoV and infectious peritonitiscoronavirus (FIPV), a highly virulent feline coronavirus, have been generated. Using FIPV as a model, it wasdemonstrated that the lead compound for FIPV reverses the progression of fatal FIP in experimentally ornaturally infected cats. Since FIP disease progression is quite rapid and its pathogenesis primarily immune-mediated, features shared by MERS-CoV, it was hypothesized that a viral protease inhibitor could reverse thepathogenesis of MERS-CoV in affected hosts. Using a structure-guided approach, the anti-FIPV compoundwas structurally modified resulting in the identification of piperidine-derived lead compounds that were found tobe highly effective against MERS-CoV. Thus, the primary goal of this R01 application is the identification of anin-vivo validated MERS-CoV preclinical candidate by conducting an array of basic and applied studies. Fouraims are proposed to achieve this objective. Specific Aim 1. Optimize the piperidine-derived lead series ofMERS-CoV 3CLpro inhibitors by iterative medicinal chemistry and structure-based drug design. Specific Aim 2.Conduct in vitro efficacy, biochemical, mechanistic, structural, spectroscopic, and computational studies toprioritize analogs, elucidate the mechanism of action, and accelerate the optimization process. Specific Aim 3.Evaluate the physicochemical properties, ADMET, PK, and oral bioavailability of optimized leads. Specific Aim4. Determine in vivo efficacy of optimized leads in mouse models of MERS-CoV infection. The ultimate longterm goal of this program is the development of antiviral therapeutics for MERS by advancing a drug candidatethrough the stage of filing for an investigational new drug (IND) application.",2020,2023,KANSAS STATE UNIVERSITY,732873,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2018 +C00994,5R01AI135270-02,Structural and functional analysis of the coronavirus spike protein fusion peptide,"Project Summary / AbstractEnveloped viruses access their host cells by binding to receptors on the plasma membrane and then undergoingfusion with the host membrane. Both binding and fusion are mediated by a specific viral ""spike"" protein that istypically primed for fusion activation by proteolytic cleavage to expose the fusion peptide. Coronavirus fusionspike protein (CoV S) is a complex biomolecular machine that has a novel fusion peptide with has a great dealof inherent flexibility in its fusion reaction. This is exploited by these viruses in their diverse entry pathways andis a primary determinant of viral tropism. We have pioneered the concept that that the proteolytic cleavage eventsin S that lead to membrane fusion occur both at the interface of the receptor binding (S1) and fusion (S2) domains(called S1/S2), as well as adjacent to a structurally and functionally novel fusion peptide within S2 (called S2').Thus, there are notable differences between CoV S and most other class I fusion proteins including: 1) that theproteolytic events liberating the fusion peptide are diverse, and 2) that the fusion peptide itself is atypical insequence compared to other fusion peptides, containing a mixture of important hydrophobic and negatively-charged residues, and may represent a larger than normal fusion ""platform"" instead of a defined ""peptide"". Thusfusion peptide activity is likely controlled by reorganization of the fusion platform, based on both hydrophobic(i.e. lipid-binding) and ionic (i.e. Ca2+) interactions. Despite the recent availability of S structures in their pre-fusion state, there remains a very limited mechanistic understanding of membrane fusion for the CoV family, orany structural information to correlate structural biology aspects of S to its function in membrane fusion. Thisinformation is critical to understanding viral pathogenesis and CoV emergence into the Human population. Wepropose an integrated biophysical, biochemical, and in vivo approach to study the unique cleavage-activatedregulation of CoV S protein, using Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acuterespiratory syndrome coronavirus (SARS-CoV) as primary models. We will use state-of-the-art spectroscopyand an innovative single particle tracking technique to study S protein fusion peptide function, and combine thesewith in vivo infectivity studies, including at BSL3, will allow a complete picture of CoV fusion activation. Theseapproaches will reveal how structure and function vary depending on the key activators of S; i.e. receptor binding,protease availability and the local ionic environment. These studies will allow us to determine common principalsthat can be applied to all CoVs, moving the field forward with these innovative studies will provide criticalknowledge about CoV entry and tropism needed to safeguard human health from an emerging pathogen likelyto cause severe outbreaks, and for which few or no medical countermeasures exist.",2020,2022,CORNELL UNIVERSITY,523463,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2018 +C00997,5R01AI137364-02,Transcriptional Profiling to Discriminate Bacterial and Non-bacterial Respiratory Illnesses,"Acute respiratory infections (ARI) occur commonly throughout life and are a leading cause of antibiotic overuse. Antibiotic use is directly linked to spread of antimicrobial resistance, which is now considered to be one of the most urgent threats to global public health. In most cases of ARI antibiotics, the microbial etiology is unknown and antibiotics are administered empirically and often inappropriately. Although sensitive molecular diagnostics allow rapid diagnosis of a variety of respiratory viruses, their impact on patient management and antibiotic prescription has been modest primarily due to concern about bacterial co-infection. Sensitive and specific diagnostic tests for bacterial lung infection are currently lacking. Gene expression profiling of whole blood represents a powerful new approach for analysis of the host response during infection. Preliminary studies using microarrays indicate that viruses and bacteria trigger specific host transcriptional patterns in blood, yielding unique ""bio-signatures"" that may discriminate viral from bacterial infection. Although encouraging, studies to date have not produced predictive gene sets with sufficient accuracy required for use in clinical medicine. Importantly, subgroups of patients with underlying conditions, specific clinical syndromes and those with mixed viral-bacterial infections have not been resolved by gene expression signatures. It is likely that the accuracy of diagnostic predictive gene sets can be optimized by analyzing transcriptional profiles while accounting for these host and clinical factors. This project will evaluate optimal blood predictive gene signatures using RNA sequencing in adults hospitalized with ARI to distinguish bacterial and nonbacterial illness in the presence of preexisting lung disease including asthma and chronic obstructive pulmonary disease as well as for pneumonia vs. non-pneumonic syndromes. Illnesses that have adjudicated diagnoses of viral alone, bacterial alone or mixed viral-bacterial infection will be selected for RNA sequencing and data used to develop a predictive model to discriminate bacterial and nonbacterial respiratory illness. The goal of this study is to define a limited number of host predictive expression genes that can be developed into a rapid point of care diagnostic and can be used by clinicians to discriminate bacterial and nonbacterial illness to optimally manage patients presenting to the hospital with respiratory symptoms. If successful, this approach could be extended to and validated in outpatients and other age groups in the future for maximal impact on patient care and antibiotic prescription. Given the impact of the SARS-CoV-2 pandemic on ARI, we will perform a short-term sub-study applying our methodological approaches to identify correlates of disease severity specifically in COVID19 patients.",2020,2024,UNIVERSITY OF ROCHESTER,761271,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Immunity",2019 +C00998,5R01AI137472-03,Rational design and evaluation of novel mRNA vaccines against MERS-CoV,"AbstractTraditional strategies of vaccine development suffer from long-term and costly manufacture, and as a result,often fail to respond rapidly to newly emerging and reemerging infectious diseases. By contrast, messengerRNA (mRNA) is rising as a new technology platform to develop vaccines ""on demand"" against viral pathogens,offering attractive advantages such as cell-free production, non-viral delivery, as well as simple, fast and cost-effective manufacture. Further improvement upon mRNA's stability and translation efficiency, understanding oftheir immune mechanisms, and evaluation of their protective efficacy will facilitate the development of next-generation mRNA vaccine technologies against diverse viral pathogens. Middle-East respiratory syndrome(MERS) coronavirus (MERS-CoV) is a highly pathogenic, emerging infectious virus posing a continuous threatto public health worldwide. There are currently no MERS vaccines approved for use in humans. MERS-CoVspike (S) protein, particularly its receptor-binding domain (RBD), is an important vaccine target. We havepreviously shown that MERS-CoV RBD contains a critical neutralizing domain capable of inducing strongcross-neutralizing antibodies and protecting human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice againstMERS-CoV infection with outstanding efficacy. However, production of subunit vaccines and other traditionalvaccines has limitations, such as low expression and complex purification. To address these unmetchallenges, we propose to rationally design and evaluate novel mRNA vaccines, using MERS-CoV as a modelpathogen and MERS-CoV S protein as a target antigen. We hypothesize that with appropriate modificationand optimization, MERS-CoV S protein RBD-based mRNA vaccines will demonstrate improved stability,increased translation efficiency, and enhanced immunogenicity in both mouse and non-human primates (NHP)models, with protective efficacy on par with the RBD-based subunit vaccine. The specific aims are to (1)rationally design MERS-CoV mRNA vaccines with improved stability and translation efficiency, (2) carefullyoptimize mRNA formulations and immunization regimens towards in-vivo evaluation of their immunogenicityand mode of action in wild-type mice, and (3) comprehensively evaluate protective efficacy of MERS-CoVmRNA vaccines and elucidate their protective mechanisms in hDPP4-Tg mice and NHPs. Of note, we will alsoexamine the utility of new technologies such as microfluidics and next-generation sequencing (NGS) analysisof B-cell response in mRNA vaccine development and evaluation. The long-term goal is to develop a safeand effective mRNA vaccine that is able to (1) maintain sufficient quantity and quality suitable for industrial-scale production, and (2) meet the WHO Target Product Profiles for rapid onset of immunity in outbreaksettings and long-term protection of people at high ongoing risk of MERS-CoV. Together, the proposed projectwill shed light on protective mechanisms of mRNA vaccines, and provide much-needed information andguidelines for developing mRNA vaccines against diverse viral pathogens with pandemic potential.",2020,2023,NEW YORK BLOOD CENTER,816658,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2018 +C00999,5R01AI139092-03,Structure-based design of coronavirus subunit vaccines,"Project SummaryViral subunit vaccines are safe and convenient, but generally suffer low efficacy. Our overall hypothesis is thatan intrinsic limitation is associated with subunit vaccine designs in which artificially exposed surfaces of subunitvaccines contain epitopes unfavorable for vaccine efficacy. The receptor-binding domain (RBD) of acoronavirus spike protein consists of a core subdomain that serves as the structural scaffold and a receptor-binding motif (RBM) that binds the receptor and contains neutralizing epitopes. The RBDs are primecandidates for subunit vaccine designs. In preliminary studies, we identified epitopes on the core subdomain ofMERS coronavirus (MERS-CoV) RBD that were buried in the full-length spike protein but became artificiallyexposed in recombinant RBDs. We further showed that these epitopes severely reduce vaccine efficacy byinducing strong non-neutralizing immune responses and distracting the host immune system from reacting tothe neutralizing epitopes on the RBM. This novel finding reveals an intrinsic limitation of viral subunit vaccinesthat the vaccine field had been unaware of. In this proposal, we aim to characterize this intrinsic limitation andestablish novel approaches to overcome it. We use the RBDs from highly pathogenic coronaviruses, includingMERS-CoV and SARS coronavirus (SARS-CoV), as the model system. This proposal contains three majordesign approaches for coronavirus RBD vaccines. First, we will identify and characterize the artificiallyexposed unfavorable epitopes on the core subdomain of coronavirus RBDs. To this end, we introduce a novelconcept, neutralizing immunogenicity index (NII), to evaluate the contribution of each epitope to the overallvaccine efficacy. We will mask the negative epitopes on the core subdomain through glycan shielding orresurfacing. This design enhances the efficacy of the individually optimized RBD vaccines. Second, we willconstruct chimeric RBDs containing the core subdomain from one coronavirus RBD as the structural scaffoldand the RBM from another coronavirus RBD as the immunogenic sites. The unfavorable epitopes on the coresubdomain should have been silenced from the first design approach. The interface of the core subdomain andRBM will be optimized to maximize the stability of the chimeric RBD vaccines. This design prepares us for theemergence of highly pathogenic coronaviruses in the future. Third, we will construct nanoparticle-carriedcoronavirus RBD vaccines in a way that artificially exposed unfavorable epitopes on the core subdomain arere-buried at the molecular interfaces to enhance the RBD vaccine's efficacy. We will use mice to evaluate theimmunogenicity of the above engineered RBD vaccines and will use animal models (including hDPP4-knock-in(KI)) mice and non-human primates) to assess the selected RBD vaccines against live coronavirus challenge.Overall, this research establishes the artificially exposed unfavorable epitopes as the intrinsic limitation of viralsubunit vaccines and finds novel approaches to overcome it. Therefore, this research holds the promise ofmaking subunit vaccines a more successful and widely used strategy in combating virus infections.",2020,2023,NEW YORK BLOOD CENTER,839218,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2018 +C01000,5R01AI141607-02,Development of a High-Throughput Microfluidics-Enabled Functional Assay for Rapidly Identifying Neutralizing Antibodies,"ABSTRACT Viral pathogenesis kills 100 million people each year. However, broadly neutralizing antibodies (Abs) pro-duced by B lymphocytes in fortunate hosts routinely eliminates the threat of the most lethal viruses. Identifyingthe antigenic epitopes that can induce such neutralizing Abs (nAbs) via immunization is at best protracted andfraught with technical challenges, if possible at all. We are developing a novel, microfluidic, lab-on-a-chip tech-nology to radically speed the ability to functionally assay the neutralization capability of clonal Ab produced byone human B cell. PRESCIENT (Platform for the Rapid Evaluation of antibody SucCess using Integrated mi-crofluidics ENabled Technology) is a high-throughput, single-cell resolution platform that can measure the neu-tralization capability of the Abs produced by single B lymphocytes through a direct functional assay in a dropletmicrofluidics format. Thus, it provides an unbiased, single-cell resolution, high-throughput, near-complete anal-ysis of the entire B cell repertoire to identify B cells that neutralize viral infection. As influenza sometimes causes one half million deaths per year and we have a battery of tools and rea-gents already developed for this pathosystem, we have chosen it as the viral model in which to test our centralhypothesis that PRESCIENT will deliver a fast and low cost route for discovering neutralizing Abs (nAbs). Wewill take a tripartite approach with these aims: 1) to optimize the performance of the device with greater reliabil-ity, throughput and efficiency, 2) to quantitatively assess PRESCIENT's ability to recognize hybridomas thatmake nAbs against H1N1 influenza from progressively more rigorous mixed populations, and 3) to rapidly iden-tify nAbs against H1N1 and H3N2 influenza from EBV-immortalized human peripheral blood B cells. Phage and other display systems commonly used for nAb discovery have inherent bias and protein produc-tion hurdles due to non-mammalian post-translational modifications, thus direct utilization of B cells is ideal.Droplet microfluidic systems, where pico-liter scale water-in-oil emulsion droplets function as independent bio-reactors, can efficiently manipulate cells with unprecedented speed and precision. Droplet microfluidic systemsfor screening Abs produced from hybridomas that inhibit specific biochemical reactions have been described.However, systems that integrate Ab screening and viral neutralization bioassays have not yet been achieved.The major innovation is the development and utilization of the first high-throughput system for the functionaldiscovery of human nAbs against infectious agents, a truly vertical leap for the fields of vaccinology, immuno-therapeutic design and epitope discovery. With PRESCIENT, immunologists will be able to rapidly identify froma convalescent patient's blood draw the ""needle in the haystack"" paratope that generates life-saving broadlyneutralizing Abs. Ultimately, the unique immunoglobulin heavy and light chain DNA rearrangements will be iso-lated from the PRESCIENT-sorted cell for monoclonal Ab production or structural vaccine epitope engineering.1",2020,2024,TEXAS A&M UNIVERSITY,719651,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3,H1N1,,H3N2,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2019 +C01002,5R01GM123779-38,Electron Spin Relaxation in Model Membranes,"Abstract: This project is aimed at the study of properties of membrane proteins that underlie importantbiomedical processes and are implicated in health disorders and how they interact with their membraneenvironments. By means of the latest one and two dimensional electron-spin resonance (ESR) methodologies,including Pulse-Dipolar ESR (PDS), multifrequency ESR, and Two-Dimensional Electron-Electron DoubleResonances (2D-ELDOR), as well as site-directed nitroxide spin-labeling methods, we will directly observesignificant protein functional changes and in parallel experiments, observe the concomitant changes occurringin the dynamic structure of the lipid bilayers. This ability to accurately characterize both membrane andmembrane protein is an innovative approach toward understanding on the role of membrane-proteininteractions affecting the protein's function. Specific projects include the following. First, we will advance ourstudy of the mechanism of viral membrane fusion, based on our previous success in detecting the membraneordering effect of influenza and HIV glycoprotein fusion peptides (FP). We will extend this study to the structureof their FP-transmembrane domain complex in membranes and to quantification of the induced microdomain,plus we shall extend the study to SARS and gamete membrane fusogens. In the second project, the tauprotein, which plays an important role in neurodegeneration, will be studied. We have shown how tau interactswith membranes and adopts different conformations in response to the curvature of liposomes, so we plan tostudy the interaction between tau and microtubules, which directly addresses its functional and pathologicalroles in neurodegenerative diseases. The third project will focus on the structure of asymmetric membranes,which are crucial for cell function. We will investigate how both membrane leaflets interact with each other, andhow the changes in the composition of one leaflet affect ordering and fluidity of the other, as well as how themodel peptide gramicidin changes their structure and facilitates lipid flip-flop. In the fourth project, we will studythe influenza A M1 and M2 matrix proteins, which are related to viral infectivity and proliferation. We previouslyshowed the oligomerization of M2 TMD in membrane is a two-step process and the stoichiometry is affected byligand binding. We will focus on the effect of lipid composition on the M1 oligomerization. We will also study thestructure of the M1-M2 complex in membranes. In the fifth project, our ESR studies on the mechanism oftransmembrane signaling in bacterial chemoreceptors will be continued and extended. We will 1) characterizethe lipid dependence of the piston motion exhibited by chemoreceptors, 2) examine the effect of receptoroligomerization state and conformation on lipid structure, and 3) probe the interactions of the chemoreceptorsensing domain relative to the lipid bilayer. All these studies will involve extensive collaborations with leadingresearch groups. Possible clinical applications include detection of membrane changes during immuneresponse, prevention of viral entry, fertility diseases, neurological disorders, and development of antimicrobials.",2020,2021,CORNELL UNIVERSITY,494198,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",1978 +C01006,5R24AI120942-05,World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)," DESCRIPTION (provided by applicant): New and emerging viruses and arboviruses represent increasing threats to human health, yet their mechanisms of emergence remain poorly understood, and effective interventions are not available for most. Research on their ecology, evolution, epidemiology, emergence mechanisms, diagnostics, and development of vaccines and therapeutics remain critical public health needs. The World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) comprises a comprehensive, diverse collection of over 6,700 virus strains in 21 families, as well as antisera, antigens and other reagents to enable research worldwide. Approximately 400 new virus strains are added each year, and 1000 viruses and reagents are shipped annually. The WRCEVA also maintains broad expertise in both novel and traditional approaches to virus identification and characterization, and assists with outbreak diagnosis. This proposal seeks to continue these WRCEVA activities in support of NIH-funded and other research on emerging viruses worldwide through 5 Specific Aims: 1. Maintain a comprehensive set of emerging viruses, arboviruses and associated reagents to support research and surveillance. The virus collection as well as antigens, antibodies and other reagents will be continually enhanced to capitalize on new technology, and cDNA clones of selected strains will be added. NextGen sequencing-based quality control practices will be implemented to ensure strain accuracy/purity. 2. Discover, isolate and characterize newly acquired viruses by using electron microscopy, next generation sequencing, and serologic methods to determine relationships and taxonomic assignments, and to assess in vitro and in vivo host range. Clinical and field samples as well as viral isolates will be received for identification and characterization, and added to the repository. Critical phenotypes of newly discovered viruses and strains will be assessed by using in vitro and in vivo infections. 3. Perform sequencing and phylogenetic analyses of selected virus groups to determine evolutionary histories and emergence mechanisms, patterns of spread and infection, and to rapidly determine the sources of new outbreaks. Key virus strains will undergo genomic sequencing to generate databases that can be exploited for the rapid determination of new outbreak sources, including potential bioterrorism. 4. Characterize recently discovered mosquito-specific viruses (MSVs) and determine their evolutionary history, impact on the transmission of arboviruses, and genetic determinants of host range. Selected arbovirus taxa that include mosquito-specific viruses will be studied to understand the genetic basis of their host range restriction and assess their potential as tools to interfere with arbovirus transmission 5. Train scientists in the identification and characterization of emerging viruses and arboviruses.To further enhance research efforts in the U.S. and worldwide as well as to leverage collaborations that feed our collections, basic training in virus identification and characterizaton will be provided to qualified scientists.",2020,2021,The University of Texas Medical Branch at Galveston,728153,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2016 +C01007,5U19AI100625-08,Systems Immunogenetics of Emerging Coronavirus Infections in the Collaborative Cross,"AbstractSevere and emerging respiratory virus infections are responsible for considerable human morbidity andmortality and threaten global health. Importantly, significant individual to individual variation in immuneresponses after infection regulates disease severity, a process that is heavily influenced by natural hostgenetic variation in Human populations. In this backdrop, new paradigms are needed to achieve the promise ofprecision medicine, early disease diagnosis/prognosis, susceptibility and risk assessment, and personalizedtreatment. To address this theme, our research programs leverage forward genetic screens in the newlydeveloped collaborative cross (CC) mouse resource to map, identify, and elucidate the polygenic immuneinteractions and molecular mechanisms that govern disease severity following highly pathogenic respiratoryvirus infection. Using the SARS-CoV model, natural genetic variation in the CC expands the range andcomposition of respiratory disease phenotypes, corresponding to selective forces that have shaped humanimmunity. Aim 1 seeks to define quantitative trait loci governing immunity to SARS-CoV and related viruses.Aim 2 identifies causal gene candidates within the QTL and seeks to derive mechanistic insights. Finally, Aim 3integrates these findings across different disease models and between mouse models and human patients.Overall, the goal is to identify the mechanism by which polygenetic traits drive differential disease, to predictand then test disease outcomes in genetically distinct lines that contain different admixtures of susceptibilityloci, and to integrate these findings across diverse disease models and species.",2021,-99,University of North Carolina at Chapel Hill,428666,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity", +C01010,5U19AI142759-02,Project 1 - Coronavirus,"PROJECT SUMMARYZoonotic coronaviruses (CoVs) such as SARS-CoV and MERS-CoV are pandemic threats. MERS-CoVcontinues to cause new zoonotic and human transmission and illness with ~35% mortality. Currently, there areno FDA-approved therapies to treat any CoV. New zoonotic CoVs likely will emerge from heterogeneous viruspools in animal reservoirs, thus requiring antiviral strategies aimed at completely conserved and vulnerabletargets. CoVs rapidly select for resistance to multiple classes of inhibitors, demonstrating the need forapproaches to prevent resistance emergence. Both SARS and MERS infections manifest as severeimmunopathologic damage, potentially limiting the therapeutic window for direct-acting antivirals (DAAs).Immunomodulation in the absence of antivirals has been shown to not be beneficial and to even exacerbateSARS and MERS disease. Thus, combinations of DAAs and targeted immunomodulators may be necessary foreffective treatment of established infection. The overall goal of our program is to develop CoV antiviralstrategies that broadly inhibit known and future potential pandemic zoonotic CoVs, prevent emergenceof resistance, and extend the therapeutic window by targeting host immunopathologic responses. Theproposed research will advance preclinical development of the CoV-inhibitory nucleoside analogue EIDD-1931/2801 and other nucleoside analogues in the pipeline and test two small-molecule hits identified as highlyactive against SARS-CoV for treatment and prevention of epidemic and pre-emergent CoVs. In Specific Aim 1,the spectrum of antiviral activity and therapeutic efficacy of compounds will be defined. The antiviral efficacy,metabolism, and cytotoxicity of each compound will be determined in cultures of primary human lung cellstargeted by SARS- and MERS-CoV. The prophylactic and therapeutic efficacy of lead compounds will beevaluated in young, aged, and immunosuppressed murine models of SARS and MERS pathogenesis. InSpecific Aim 2, the mechanism of action of lead compounds and kinetics of drug resistance will be determined.The antiviral effect of compounds on virus replication, fidelity, and induction of innate immunity will be assessed.Resistance mutations in genomes of MERS- and SARS-CoV passaged in the presence of increasingconcentrations of drug will be determined by deep sequencing. The impact of resistance on SARS- and MERS-CoV virulence, sensitivity to other drugs, and therapeutic efficacy of lead compounds will be determined.Specific Aim 3 will focus on the development of combination regimens for the treatment of emerging CoVs. Thecombined therapeutic efficacy of DAAs against infections with both wild-type and drug-resistant SARS- andMERS-CoV will be defined using cultured cells and mice. The therapeutic effect of treatment combining a DAAwith an immunomodulator will be assessed in mouse models of SARS and MERS. These studies will generatemechanistic and efficacy data necessary for IND filing and origination of human clinical trials.",2020,-99,UNIVERSITY OF ALABAMA AT BIRMINGHAM,1024373,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments, +C01012,ANRS COV01,Recherche Clinique (Clinical Research) - INTENSE-COV - Évaluation de combinaisons thérapeutiques pour améliorer le pronostic de l'infection à COVID-19 et réduire la contamination en Côte d'Ivoire : un essai contrôlé randomisé de phase IIb. INTENSE-COV - Combination therapy to improve outcome of COVID-19 infection and decrease contamination of relatives in Côte d'Ivoire : a randomized controlled phase IIb study.,"Study Desing: Randomized, comparative, multicenter, phase IIb, superiority, parallel arm, unblinded trial to evaluate the efficacy and safety of two combination therapies versus monotherapy against SARS-CoV-2 for 10 days in adults living in Abidjan, Côte d'Ivoire. Main objective: To compare the efficacy of two antiviral and anti-inflammatory combination therapies versus lopinavir/ritonavir antiviral monotherapy on the reduction of nasopharyngeal carriage of CoV-2 SARS and the reduction of inflammatory syndrome during COVID-19. Inclusion criteria: Patients over 18 years of age, with an SARS-CoV-2 infection confirmed by specific PCR, with clinical manifestations of the infection, such as fever or cough or ENT signs or breathing difficulties, Naïve to specific treatment for COVID-19,Women of childbearing age should accept the use of mechanical contraception during the study period, Informed consent signed by the patient. Trial treatments Participants will be randomized into 3 groups: - Group 1: lopinavir/ritonavir - Group 2: lopinavir/ritonavir + telmisartan - Group 3: lopinavir/ritonavir + atorvastatin The duration of treatment will be 10 days in each treatment group. Primary Endpoint : Proportion of patients with undetectable nasopharyngeal swab SARS-CoV-2 PCR and CRP < 27 mg/L at D11. *Number of participants: 294 (98 per treatment group).",2020,-99,"Université de Bordeaux, PACCI",321440,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Africa,Africa,,,,Cote d'Ivoire,Cote d'Ivoire,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Phase 2 clinical trial",2020 +C01013,ANRS COV02,Recherche Clinique (Clinical Research) - Prévalence du Covid-19 chez les jeunes enfants hospitalisés avec pneumonie sévère ou malnutrition aiguë sévère en Afrique sub-saharienne et Asie du Sud Est. A sub-study of TB SPEED SAM and TB SPEED Pneumonia. Prevalence of COVID-19 in young children hospitalized with severe pneumonia or severe acute malnutrition in Sub-Saharan Africa and South-East Asia.,"Although data from China, Europe and US show that children are less affected by the COVID-19 pandemic than adults,we do not know what happens when the infection occurs in immunocompromised children. Malnutrition is common in low and moderate income countries and can be associated with other frequent co-morbidities like HIV infection and sickle cell disease. Severe pneumonia remains one of the main cause of death in young children living in these countries and is also the main clinical presentation of severe COVID-19 disease in children. The TB-Speed project offers a unique opportunity to identify sub-groups of children who may be particularly affected by the COVID-19 pandemic and to propose specific measures to reduce the impact of the SARS-Cov-2 infection in these groups of children. TB-Speed COVID is an ancillary study nested in two ongoing TB-Speed studies in 6 countries in Africa and Asia: the TB-Speed Pneumonia trial that evaluates the impact of systematic detection of tuberculosis on mortality among young children admitted with severe pneumonia, and the TB-Speed SAM study that is aiming to develop a tuberculosis diagnostic algorithm for hospitalized children with severe acute malnutrition (SAM). The TB-Speed COVID study will assess the prevalence of the COVID-19 in these two groups of children at admission and its impact on children's outcomes. The 1st study group will be children below 5 years old with diagnosis of severe pneumonia according to WHO, and the 2nd group will be children younger than 5 years old, hospitalized with severe acute malnutrition defined by either weight-for-height Z score < -3 standard deviation or mid-upper arm circumference < 115 mm or clinical signs of bilateral pitting oedema. After informed consent signed by parents or guardian, nasal swab and stool will be collected and sent to referral testing laboratories for real time PCR of SARS-Cov-2. Dried blood spot will be collected at enrolment and after 3 months in infected children to assess seroprevalence and seroconversion. Clinical, biological and chest-ray data will be extracted from the TB-Speed Pneumonia and SAM studies at enrolment and during follow-up. Consecutive children included in the 15 sites of the TB-Speed Pneumonia study across 6 countries (Cambodia, Cameroon, Cote d'Ivoire, Mozambique, Uganda, Zambia) and in the 3 sites of the TB-Speed SAM in Uganda and Zambia will be enrolled in the TB-Speed COVID study over a 6 months period. We expect enrolling 1000 children with severe pneumonia and 200 hospitalized children with severe acute malnutrition.",2020,-99,N/A,132160,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS) | Expertise France,France,Europe,,Africa | Western Pacific,,,,,Cambodia | Cameroon | Cote d'Ivoire | Mozambique | Uganda | Zambia,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C01014,ANRS COV03,"Recherche Clinique (Clinical Research) - Antibioclic Afrique, un outil électronique d'aide à la décision clinique pour la prise en charge du COVID-19 en Afrique de l'Ouest Antibioclic Afrique, an electronic clinical decision support system for the management of COVID-19 in West Africa","The COVID-19 pandemic continues to spread, particularly in Africa, and a rapid increase in cases in many African countries is to be feared. On July 23, 2020, more than 114 000 cases and 1782 deaths have been reported in West Africa. Côte d'Ivoire and Senegal are among the most affected countries with 15 000 cases in Côte d'Ivoire and 9300 cases in Senegal. In order to control the epidemic, it is necessary to intervene at all levels of medical management, including primary care and working with healthcare workers who are among the most important actors in the epidemic response. However, primary care practitioners often practice in isolated settings without easy access to national recommendations, where and when they exist. It has been shown that electronic tools can help practitioners in their diagnostic and therapeutic decisions when caring for patients. However, according to the WHO, the distribution of electronic or digital health tools is still very limited in Africa. The overarching goal of this project is to improve the clinical management of COVID-19 patients in West Africa. For this, we propose to create, and make available, a free and independent electronic clinical decision support (CDSS) for the management of patients suspected or confirmed with SARS-CoV-2 infection: Antibioclic Afrique. Antibioclic Afrique would enable primary care clinicians to obtain personalized recommendations for diagnostic and therapeutic management in a few ""clicks"" adapted to each clinical situation. It would also advise them on the prevention aspects (organization of the health facility), and on the advice to give to patients. Several stages are essential for the sustainable success of this project: (i) developing an electronic tool to guide the clinical management of patients based on the architecture of Antibioclic which uses a systematic method to translate clinical recommendations into semi-formal decision trees (ii) adapting and tailoring it to the West African context in 5 different countries, taking into account the local context, the organization of the healthcare system and the diversity of health care facilities and training of prescribers (iii) implementing the CDSS guided by the use of theoretical frameworks and systematic strategies in implementation science in order to optimize the chances of success (iv) widely disseminating the tool by relying on the networks of the project investigators, of the ANRS, the African Society of Infectious Pathology (SAPI) and REACTing (v) monitoring and updating Antibioclic Afrique to provide decision support adapted to the current recommendations. This project will be associated with a research project which will aim to evaluate the implementation process, using methods drawn from implementation science. Implementation science is defined as ""the scientific study of methods to promote the systematic adoption of research results and other evidence-based practices in routine practice and, thereby, to improve the quality and 'care efficiency'. These methods are based on an assessment of the local context, the definition of interventions adapted to this context, and the evaluation of the implementation process. This methodology will aim to optimize the decision support tool by its adaptation, its usefulness, its efficiency, and its cost (development and implementation costs, the tool being free), and especially its sustainable use by primary care clinicians in West Africa. The scientific information gathered during this project will feed knowledge on the implementation of electronic decision support tools (i) in primary care (ii) in West Africa and (iii) in a pandemic context.",2020,-99,N/A,377531.84,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,Digital Health | Innovation,,,,Burkina Faso | Gabon | Cote d'Ivoire | Mali | Senegal,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health information systems",2020 +C01015,ANRS COV04,"Recherche Clinique (Clinical Research) - Organisation de la prise en charge de l'infection COVID-19 et spécificité de présentation clinique, immunologique et pronostique chez les patients drépanocytaires au Mali Organization of the management of COVID-19 infection and specificity of clinical, immunological and prognostic presentation in patients with sickle cell disease in Mali","Objectives: 1) Reduce COVID-19 dissemination at the Reference Center for Sickle Cell Disease in Mali (CRLD) and in patients' families, and optimize the management of sickle cell disease (SCD) patients infected with COVID-19, 2) describe the initial clinical specificities of COVID-19 infection in these patients and their evolution in time, 3) determine the immunological specificities of COVID infection in SCD patients. Current situation: The COVID-19 epidemic is rapidly progressing in sub-Saharan Africa where SCD is a major public health problem (defined by WHO as a health priority). As of 04/13/2020, Mali has deplored 105 cases of confirmed COVID infection and 9 deaths, these figures are probably highly underestimated due to undiagnosed cases. A massive epidemic wave is expected, to which the health system will not be able to cope adequately. Three centers have been designated for the management of COVID+ patients. On the other hand, the CRLD in Bamako is following a cohort of 12,000 SCD patients. Specific issues: Viral infections in SCD patients, particularly with pulmonary tropism, are known to trigger severe complications (vaso-occlusive crisis and/or life-threatening acute thoracic syndrome). Therefore, these patients may be considered as more fragile or at least to constitute a distinctive population in the context of a COVID infection. Thus, it is an urgency for the CRLD to establish a suitable procedure for the early identification and specific management of its COVID+ patients. At the same time, the medical teams at COVID centers are not trained to the specificities of the SCD patients' management. SCD patients present with a chronic baseline inflammation, that worsens during acute complications. It is not known whether this characteristic represents a detrimental factor during COVID infection. The implementation of dedicated strategies by highly competent multidisciplinary teams and the definition of the specificities of COVID infection in SCD patients are a priority. Methods: Collaborative research/action project between the CRLD and the 3 COVID Centers in Bamako, and in Paris: the Internal Medicine Dept. of the European Georges Pompidou Hospital, one of the French SCD Reference Centers and equipped with a dedicated COVID sector, and the UMR 1134 Inserm/University of Paris/National Institute of Blood Transfusion (INTS). Project composed of three components: 1) organizational: training of the CRLD medical staff (doctors, nurses, biologists, laboratory technicians) to identify SCD patients at the various stages of COVID infection and, conversely, training the staff of the COVID Centers in the specific aspects of patients' management, 2) clinical research: recruitment of 3 groups, matched in age +/- 5 years: 200 SCD patients admitted to CRLD emergency ward identified as suspect of COVID infection and therefore isolated in a dedicated sector (100 PCR COVID+ patients and 100 PCR COVID-), 100 non-SCD patients PCR COVID +, hospitalized at the COVID Center of the Mali Hospital, 3) translational research: characterization of the inflammatory parameters in COVID+ SCD patients in comparison to the control groups (non-infected SCD patients and non-SCD COVID+ patients ) by measuring cytokines in frozen plasmas air-shipped in dry ice to the INTS in Paris. Work schedule: July 2020 (M8): ethics committee, construction of the database, M9-M11: recruitments, standard clinical and biological monitoring, implementation of the database, creation of the plasma library; M12: measurement of plasma cytokines, analysis and exploitation of the results. Expected results: 1) Control the spread of the COVID-19 epidemic and reduce mortality in the particularly fragile population of SCD patients in Mali, 2) Demonstration of the epidemiological and clinical features linked to COVID-19 infection of SCD patients in the African context, 3) Define the inflammatory profiles of the 3 groups studied in Africa where the population is permanently exposed to high infectious pressure.",2020,-99,N/A,88197.76,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Mali,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C01016,ANRS COV05,Recherche Fondamentale (basic research) - Identification des défauts monogéniques de l'immunité responsables des formes sévères d'infections à SARS-CoV-2 chez les patients précédemment en bonne santé Search for inborn errors of immunity underlying severe SARS-CoV-2 infections in previously healthy individuals,"The major role of human genetic variability in immunity to infection is now well established, in particular for viral infections. We have identified a number of monogenic inborn errors of immunity (IEIs) underlying life-threatening viral diseases, such as herpes simplex virus encephalitis, fulminant viral hepatitis, severe cytomegalovirus primary infection, and severe influenza pneumonitis. In December 2019, a pneumonia due to a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China, and quickly spread world-wide with an increasing number of cases and deaths. In populations naive to this new pathogen, there has been stunning inter-individual variability among infected individuals, ranging from asymptomatic infection to lethal coronavirus infectious disease-19 (COVID-19). Two groups are at high risk of severe disease: elderly people (>70 years) and patients with a pre-existing condition (including but not limited to cardiovascular and pulmonary diseases, diabetes and obesity, liver or kidney dysfunctions, and overt immunodeficiency). Among patients under 40 years, the case-fatality ratio is < 0.2%. The proportions of severe cases are probably even smaller among all infected individuals (currently unknown in the absence of serological data). Only a small proportion of otherwise healthy, young people therefore fail to control SARS-CoV-2 infection. In this context, we hypothesize that life-threatening COVID-19 in previously healthy individuals younger than 50 years can be caused by IEIs. To test this hypothesis, our project will tackle three specific aims: 1) to recruit otherwise healthy young patients with severe COVID-19 in France, and in three countries from Latin America, Mexico, Colombia, and Brazil (and their family members when available); 2) to search for candidate disease-causing variants using a cutting-edge strategy developed in our laboratory to analyze whole-exome sequencing data of patients and controls (including asymptomatic infected subjects); and 3) to perform in-depth functional studies to characterize the products of the candidate variants biochemically, and to analyze the corresponding patients' cells immunologically. Our highly innovative project is feasible, as it is based on a unique collection of patients, with stringent inclusion criteria, the longstanding collaboration of the French partner with the four Latin America partners, and benefits from the unique expertise of the French laboratory in the discovery of IEI underlying severe infectious diseases. The immunological implications of our project are considerable, as we will discover the pathogenesis of severe, unexplained COVID-19, thereby revealing essential circuits involved in host defense against SARS-CoV-2. Our project should also facilitate genetic diagnosis and counseling, including specific preventive measures, while paving the way for the development of novel preventive and therapeutic strategies including anti-viral drugs (e.g. aimed at restoring a deficient immunity) and vaccines (e.g. aimed at boosting certain immunological pathways).",2020,-99,N/A,212240,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Americas | Europe,,,,,Colombia | Brazil | Mexico | France,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis", +C01017,ANRS COV06,"Recherche Fondamentale (basic research) - AFRICoV - Veille génomique des virus SARS-CoV-2(-like) sur les marchés de viande de brousse africains, et perceptions des risques sanitaires liés au COVID-19 et à la consommation de viande de brousse AFRICoV-- Genomic surveillance of SARS-CoV-2(-like) viruses in African bushmeat markets, and perceptions of health risks related to COVID-19 and bushmeat consumption","Because the COVID-19 outbreak originated from a Chinese ""wet market"", the illegal wildlife trade has been hold for the prime responsible of the current pandemic. SARS-CoV-2-like strains have so far been isolated in two Asian mammals, a bat and a pangolin. Given the diversity of SARS-CoV viruses and their acknowledged ability to jump the species barrier, it is reasonable to consider that most of the SARS-CoV-2-like diversity spectrum remains to be described. Such knowledge gap could explain the current incapacity to describe the transmission pathway that allowed the infection of humans, the most privileged scenario being that of multiple recombinations among SARS-CoV-2-like strains in (unknown) intermediary hosts. Because the unsustainable harvesting of wildlife has a direct impact on the propagation of emerging diseases, wildlife trade surveys constitute crucial sentinels for the surveillance of future SARSCoV- 2-related outbreaks. Bushmeat (wild game) consumption is a major cultural practice in tropical Africa and has been the source of deadly zoonotic diseases such as HIV, Ebola and Lassa fever. Although SARS-CoV- 2-like viruses are yet unknown in tropical Africa, we posit that available evidence supports the hypothesis that SARS-CoV-2-like virus diversity has remained largely unscreened in mammals and that a huge knowledge gap in tropical Africa remains to be filled. All the more since the only mammals so far screened positive to SARS-CoV-2-like in Asia also have representatives in tropical Africa (pangolin and horseshoe bat). Because in the context of the COVID-19 pandemic surveying reservoirs and wildlife trade practices is a prerequisite to efficient health surveillance, AFRICoV tackles the issue of SARSCoV- 2 infection from the original prism of the reservoirs as part of the wildlife (bushmeat) trade established in Africa - and recently linking the African continent to Asia (through pangolin trafficking). Our general objective is to conduct health surveillance and risk assessment for a potential next SARS-CoV-2-related pandemic in tropical Africa linked to bushmeat consumption and trade. This is especially relevant in the African context given the general lack of awareness of populations regarding health issues linked to bushmeat consumption. AFRICoV aims to understand the pathways of infection between animals to humans through four main objectives: (i) assessing the prevalence of SARS-CoV-2-like viruses in mammals from tropical Africa, Specific objectives: - Systematic screening of SARS-CoV-2-like viruses in the widest possible spectrum of African mammals sold in the bushmeat market - Intensive screening of the African counterparts of the known Asian hosts (pangolins and horseshoe bats) (ii) characterizing the evolution of SARS-CoV-2, Specific objectives: - Genome assembly of SARS-CoV-2-like viruses - Phylogenomic analysis and datation among SARS-CoV-2-like strains - Characterization of evolutionary rates and recombination events (iii) anticipating a new SARS-CoV-2 reservoir in sub-Saharan Africa, Specific objectives: - Patterns of species-to-species infection during the evolution of SARS-CoV-2-like viruses (among wild mammals) and in the recent time (SARS-CoV-2; from humans to domestic / captive animals) - Detection of putative recombination in the recent time (between humans and domestic / captive animals) (iv) implementing efficient measures protecting African people from new zoonotic diseases. Through AFRICoV, we propose a multi-disciplinary approach linking genomic characterization of new SARS-CoV-2-like viruses, health surveillance of mammalian reservoirs and the study of bushmeat stakeholders' perceptions on the COVID-19 pandemic and its link with wildlife consumption, through an unprecedented comparative approach among three countries (Cote d'Ivoire, Benin and Cameroon). Members of the AFRICoV project have a demonstrated, longterm expertise in wildlife trade surveys, involving genetic / genomic surveys of mammalian hosts and their pathogens and the study of bushmeat stakeholders' representations and awareness on zoonoses linked to the wildlife trade. Such long-term upstream work provides an exceptional opportunity to access the bushmeat market network in Africa and assess the health risks associated to SARS-CoV-2-like viruses and bushmeat consumption. The main outputs from AFRICoV will include a better understanding of SARS-CoV-2-like virus evolution in mammals, an unprecedented estimation of SARS-CoV-2 reservoirs in Africa, the validation of an RT-PCR assay for screening SARS-CoV-2(-like) viruses in mammalian reservoirs, South-to-South training in the rapid diagnostic of SARS-CoV-2(-like) viruses (RT-PCR), educative material associated to bushmeat consumption and public health (leaflet and diffusion to national Medias), and a regional restitution workshop in western Africa including policy makers.",2020,-99,N/A,384123.04,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Cote d'Ivoire | Cameroon | Benin,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2021 +C01018,ANRS COV07,Recherche Fondamentale (basic research) - Marqueurs prognostiques muqueux et systémiques de la résistance versus la tolérance dans la pandémie COVID-19 Mucosal and systemic clinical prognosis markers of resistance and tolerance in COVID-19,"Coronavirus disease 2019 (COVID-19) pandemic is due to infection with SARS-CoV2 coronavirus and represents a major public health threat, due to unusual rapidity of viral spreading in humans, severity of symptoms and mortality rate. Recent data reveals that the clinical outcome of SARS-CoV2 infection can vary greatly among individuals, from asymptomatic to mild symptoms, severe symptoms or critical conditions. The reasons underlying this variation in the clinical outcome remain unknown. There are two main ways a host deals with infection. One is through resistance, the ability to restrict or eliminate the infectious agent. This function is primarily performed by the immune system. The second, disease tolerance, is the capacity of the host to avoid or restrict the pathological consequences of an infection. The rate of contamination by virus spreading to highly exposed healthcare professionals has been dramatic. Through longitudinal multi-parametric and pathophysiological analysis, the study will provide directly in human, the proof of the concept that disease tolerance allows for homeostatic protection against an ongoing viral infection in such emerging pandemic infection. We speculate from past experience and know-how on mucosal regulatory pathways maintaining protection and homeostasis against viral infections, that IgA and Treg/Th17 division of labor is essential both for controlling virus and at the same time ensuring a safe host responsiveness, with minimal collateral damage, from onset to end of infection and resolution of disease. The clinical follow up of the individuals, from early onset mild clinical symptoms to more severe pathological signs (respiratory failure, morbidity, mortality), will allow to retrospectively identify severity and risk individuals associated to failure of disease tolerance mechanisms. This knowledge should help to better control COVID-19 pandemia and would provide a scientific basis, un-valuable for identifying individuals that should benefit from therapeutic intervention and/or vaccination strategies.",2020,-99,N/A,294479.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Americas,,,,,Brazil,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C01019,ANRS COV08,Recherche Fondamentale (basic research) - Surveillance de la circulation du SARS-CoV-2 dans les chauves-souris Rhinolophes au Bangladesh et génération de modèles d'étude cellulaire (SARSRhinCell) Monitoring of the circulation of SARS-CoV-2 in Rhinolophus Bats in Bangladesh and generation of cell models for in vitro studies (SARSRhinCell),"The current COVID-19 pandemic is caused by the SARS-CoV-2 virus. This betacoronavirus, like its predecessor named SARS-CoV1, is thought to be carried by Rhinolophus bats. The territory covered by these bats extends from Japan to Great Britain. The circulation of SARS-CoV2 in Rhinolophus bats around the world and especially near China as in Bangladesh is not known. In this country where the highly lethal Nipah virus already emerges from other bats every year, the circulation of SARS-COV2 could represent a major risk of new emergence. Thus, deciphering the mechanisms of the antiviral antiviral response that allow the natural host not to develop symptoms is an unavoidable challenge today. Here we propose to assess the prevalence and the risk of emergence of SARS-CoV-2 in Bangladesh and to develop Rhinolophus sp based cellular tools which will be essential for studying the virus-natural host interactions. This study will also allow generating banks of Rhinolophus tissue, cell lines and circulating coronaviruses in Bangladesh. A better assessment of the risks of future viral outbreaks can thus be carried out.",2020,-99,N/A,240216.48,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Europe | South-East Asia,,,,,Bangladesh | France,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Animal source and routes of transmission,2021 +C01020,ANRS COV09,Recherche Fondamentale (basic research) - Développement d'anticorps monoclonaux dirigés contre le domaine de fixation au récepteur (RBD) de cOVID-19 et caractérisation de leur réponse neutralisante à large spectre Generation of potent cross-neutralizing monoclonal antibodies against the receptor binding domain of COVID-19 virus,"April 2020, the COVID-19 pandemic has causes more than 100 000 death worldwide. Therapeutics and development prophylactic vaccine are urgently and desperately needed. The aim of this project is to decipher the benefice of antibodies (Ab) directed against the receptor-binding domain (RBD) of COVID-19 as therapeutic or in vaccine strategies. This domain that directly interact with the host angiotensin-converting enzyme 2 (ACE2) receptor was previously proposed to be a relevant therapeutic and vaccine immunogen. Monoclonal Abs directed against the RDB of Middle East respiratory syndrome (MERS) coronavirus, responsible for the 2012 epidemic in Middle East, have shown interesting cross-neutralizing activities. However, these mAbs have only mild cross reactivity with the new coronavirus emerged in 2019, further suggesting that COVID-19 RBD display particular features. Moreover, as some potentially deleterious enhancing effects were described in vitro for certain RDB MERS-Cov specific antibodies, in depth characterization of the functional profile of the newly generated mAb is required. A strong collaboration between C. Moog's lab (U1109 INSERM) and F. Shokri's lab (Tehran University of Medical Sciences) will be developed to perform an in depth characterization of the functional activities of the Abs generated. As a second step, the potential efficacy of the most promizing mAbs generated will be tested in vivo using intranasally COVID-19 infected BALB/c mice transgenic for human ACE2 and CD147. The identification of RBD specific mAbs displaying functional cross-inhibitory activity against COVID-19 without deleterious toxic or enhancing effects will give clues for the use of such type of Abs for therapeutic intervention and will guide us for the development of vaccine immunogens.",2020,-99,N/A,171360,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Eastern Mediterranean | Europe,,,,,Iran | France,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C01021,ANRS COV10,"Recherche Fondamentale (basic research) - Prevalence, diversité génétique et distribution géographique des coronavirus chez les chauves souris sauvages afin d'évaluer le risk pour de futur transmissions zoonotiques Prevalence, genetic diversity and geographic distribution of coronaviruses in wild bat populations in their natural habitat to evaluate risk for futur cross-species transmissions to humans.","The majority of EID are dominated by zoonoses and >70% of zoonotic EID events are caused by pathogens from wildlife origin. The actual COVID-19 epidemic with the SARS-CoV2 virus clearly illustrates the global damage of a single cross-species transmission from an animal coronavirus leading to a lock down of 4 billion people across the globe in a few months only. Bats have been confirmed to be the origin of human CoVs, either directly or by an intermediate host. Contacts between humans and bats are diverse, and range from direct exposure to infected blood or tissues through hunting and butchering, or indirect exposure to bat guano or fruit contaminated by their saliva, urine or faeces. A wide diversity of bat species are hunted for food or medicine, and bushmeat hunting is increasingly recognized inWest and Central Africa. Therefore, documenting the prevalence and genetic diversity of coronaviruses in bats is now more than crucial. The general objective of the project is to provide new on coronaviruses in bats in African countries with high likelihood for emergence of zoonotic infections from bats. Overall we will (i) document the genetic diversity and evolution of coronaviruses in African bats; (ii) develop a high throughput serological assay to study antibodies to different coronaviruses and estimate prevalence of coronaviruses in different bat species and (iii) study seasonality of coronavirus shedding in bats. From previous studies in Guinea, Cameroon, the Democratic Republic of Congo (DRC) and Zimbabwe, we have already samples from >10,000 bats in their natural habitat available (Dried blood spots, oral and anal swabs, and fecal samples). Retrospective screening for presence of coronaviruses will be done by amplifying and sequencing of a 440bp fragment of RdRp. On a subset of samples, additional sequence efforts will be done to obtain sequences from larger genomic fragments (especially in genes that are important for serological assays (S and/or N genes) or near full-length genomes using MinION technology. We will use a high throughput serological assay (Luminex approach) to detect antibodies to coronaviruses (SARS-CoV1, SARS-CoV2, MERSV, ..) to screen bat samples in which no viral RNA could be amplified for the presence of antibodies. Like other pathogens, it is possible that coronaviruses also exhibit highly seasonal circulation patterns and occasional sampling may not be sufficient for detecting coronavirus RNA or antibodies. Samples from bat colonies in Cameroon and Guinea, collected during monthly follow-up over a one year period will be analyzed for presence of viral RNA in shedding and for antibodies to document seasonality of viral shedding in different species. Overall, this study will rapidly provide key informations on the genetic diversity of coronaviruses in bats in Africa and estimates on their prevalence. This is the first study to look for coronavirus infection rates at a large scale in bats across Africa and using the same technologies for molecular and serological screening allowing thus comparison of results between geographic areas and species. The study will provide information on proportions of bats that are shedding virus, have been infected with the virus and on seasons when viral shedding is highest for zoonotic transmissions. The information obtained by this project will also contribute to development of an appropriate diagnostic platform that can include a large panel of broadly reactive and specific antigens covering as much as possible the diversity of coronaviruses to rapidly identify circulation of new coronaviruses in humans as well as development of broad-spectrum vaccines. Similarly, additional information on targets of antiviral drugs for a wide diversity of coronaviruses with zoonotic potential will be useful to identify eventual activity of existing and new drugs.",2020,-99,N/A,308788.48,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Guinea | Cameroon | Congo | Zimbabwe,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2020 +C01022,ANRS COV11,"Recherche Fondamentale (basic research) - BamaCoV - Étude de l'épidémie de SARS-CoV-2 dans les services hospitaliers de Bamako, Mali BamaCoV: Study of SARS-Cov-2 outbreak in hospital departments of Bamako, Mali","The new coronavirus known as SARS-Cov-2 (severe acute respiratory syndrome -coronavirus 2) was first reported in December 2019. Its spread is such that it has since been declared pandemic and represents a public health emergency. Europe quickly became heavily impacted by the virus, now joined by America, areas where political and health authorities are trying with great difficulties to contain the epidemic that seriously affects elderly or co-morbid people. The COVID-19 pandemic is likely to affect many sensitive regions with fragile health care systems, such as Africa. Indeed, 2230 cases have already been confirmed in Mali so far, affecting every region. Bamako is the most impacted city. Caregivers, in the front line of Covid19 patient management, may accidentally become infected and a source of infection during the incubation phase or in case of asymptomatic infection. The objectives of this project are thus i) to limit SARS-Cov-2 spread over the hospital departments of Bamako by carrying out a systematic molecular screening of symptomatic persons (patients/caregivers) or confirmed cases contacts and by highlighting transmission clusters, and ii) to evaluate the feasibility of Point-Of-Care molecular assays in Mali. In addition, iii) viral spread and immunity acquired from SARS-Cov-2 among health workers through serological testing, allowing also the assessment of asymptomatic caregivers rate and absence of re-infection among the immunized caregivers. Finally, iv) variability of the virus over time and spread of different variants around the world will be studied by sequencing the viral genome. The data obtained during this collaborative work will better characterize the COVID19 infection in Bamako and will give the opportunity to struggle against in real time, while it seems essential to limit as much as possible the spread of the virus in developing countries. Our project also aims to improve our virological knowledge about this emerging virus.",2020,-99,N/A,117725.44,Human Populations,Black,Unspecified,Unspecified,Unspecified,Caregivers | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Mali,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics",2021 +C01023,ANRS COV12,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - COVIDCent : Situation épidémiologique, risques de propagation du COVID-19 en Afrique Centrale et apport des tests rapides point-of-care Current epidemiological situation, risks of rapid spread of COVID-19 in the Central African region and role of point-of-care rapid tests (COVIDCent study)","The Coronavirus Disease 2019 (COVID-19) represents one of the greatest health challenges of this century globally. The current data presents a critical and alarming situation in Asia and Europe. The dramatic evolution of this pandemic in the regions of the world best prepared for such a situation makes the African continent fear an uncertain prospect. The African continent currently presents extremely fragmented data, which does not allow defining the state of the epidemic on the continent. Without this information, it is and will be difficult, if not impossible, to develop appropriate strategies and responses to prevent, contain and eliminate the pandemic on the continent. The main objective of this study is to contribute to the development of new surveillance strategies, more suited to the context of the resource-limited settings as Sub-Saharan Africa and to model the state and progression of the epidemic in the region using these data. Data on the proportion of circulating specific antibody to SARS-CoV-2 in the communities will be of particular importance. We are articulating our research in particular on the performance, the contribution and the role of rapid diagnostic tests in the diagnosis and epidemiological surveillance of COVID-19 in Sub-Saharan Africa. The study will be conducted in Central Africa, in two countries, Gabon and the Republic of Congo. These two countries are facing a rising epidemic like many other countries in the region and can serve as research sites for the definition of strategies that can be applied to other countries in the region. This research will allow us to fill an important gap in the current strategy for understanding and responding to the COVID-19 epidemic.",2020,-99,N/A,266038.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Congo | Gabon,Epidemiological studies,Disease transmission dynamics,2021 +C01024,ANRS COV13,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - EMuL-COVID-19 : Étude multidisciplinaire de recherche sur le COVID-19 au Burkina Faso EMuL-COVID-19: A Multidisciplinary study against COVID-19 in Burkina Faso,"The overall aim of this research is to generate epidemiological, sociological and anthropological knowledge that will support Burkina Faso in its current response to the SARSCoV- 2 epidemic. Primary objectives - Determine the cumulative incidence (Seroprevalence) of SARS-CoV-2 infection in the general population of Burkina Faso (component 1: sero-epidemiology); - Determine the predictive factors for the occurrence of severe complications to COVID- 19 and describe the prognostic factors for death in patients admitted in the COVID-19 reference centers in Burkina Faso. This score will include the patients sociodemographic and clinical characteristics at the hospital admission (component 2: clinical epidemiology); - Analyze the therapeutic itinerary and the experience of confirmed COVID-19 cases that have been treated in the reference centers as well as the perceptions, acceptability and application of the preventive strategies by the general population. (component 3: socioanthropology).Secondary objectives - Determine the seroprevalence of SARS- CoV-2 infection in the general population by age and gender (component 1); - Determine the fraction of asymptomatic infections in the population (presence of antibodies in patients without clinical signs of SARS- CoV-2 infection) by age and gender (component 1); - Determine the risk factors for infection by comparing the characteristics of infected and uninfected individuals (component 1); 2 - Describe the sociodemographic, biological and clinical characteristics of patients with SARSCoV-2 infection in Burkina Faso, including gender, age and co-morbidities (component 2); - Determine prognostic factors for death in patients with COVID-19 (component 2); - Analyze the therapeutic itinerary of patients admitted to the main COVID-19 management centers in Burkina Faso (Ouagadougou and Bobo-Dioulasso) (component 3); - Analyze the perceptions and psychological experiences of confirmed cases, their relatives and health workers on the system implemented for the management/care of patients (pre- and post-examination counselling, care, etc.) (component 3); - Review/identify the national strategies for the prevention of COVID-19 and identify the perceptions of the population on the relevance of these strategies as well as their acceptability and application (component 3).Methodology Mixed (quantitative and qualitative) ambispective (using retrospective and prospective data), non-comparative multicenter (Ouagadougou and Bobo-Dioulasso) study in Burkina Faso.Sample size 1000 people for component 1 45000 people for component 2 100 people for component 3Outcomes Primary outcomes: • Proportion of people carrying specific antibodies to the SARS-CoV-2 virus; • Proportion of severe complications (defined as the occurrence of severe lung disease, acute respiratory distress syndrome, sepsis or septic shock) in COVID-19 patients; • Proportion of deaths in COVID-19 patients. Secondary outcomes: • Proportion of people carrying SARS-CoV-2 specific antibodies by age and gender; • The proportion of asymptomatic infections (presence of antibodies without clinical symptoms of SARS-CoV-2 infection) by age and gender; • Proportion of COVID-19 complications by age and gender • Proportion of COVID-19 death by age and gender • Acceptability and application of infection prevention strategies by the population. Eligibility Inclusion criteria Component 1: sero-epidemiological - Be 18 years of age or older, - Live in a household identified in the enumeration areas selected to participate in the study in the cities of Ouagadougou or Bobo-Dioulasso, - Have signed the informed consent form Component 2: clinical epidemiology 3 - All patients with COVID-19 hospitalized or discharged from the COVID-19 treatment reference centers in Ouagadougou and Bobo Dioulasso. Component 3: socio-anthropological - 18 years of age and over; - Patients who had COVID-19 and discharged from the COVID-19 treatment reference centers in Ouagadougou and Bobo Dioulasso; - Caregivers (wives / husbands, children etc.) of the patients with COVID-19 hospitalized or discharged from the COVID-19 treatment reference centers in Ouagadougou and Bobo Dioulasso; - Healthcare professionals involved in the care of COVID-19 patients in the treatment reference centers in Ouagadougou and Bobo Dioulasso (nurses, laboratory technicians, physicians) No-inclusion criteria Component 1: sero-epidemiological - People aged 18 and over who will refuse to participate in the study in the selected areas in Ouagadougou and Bobo-Dioulasso. - People under guardianship, trusteeship or future protection mandate. Component 2: clinical epidemiology - Patients hospitalized in referral hospitals in Ouagadougou and Bobo-Dioulasso and treated for COVID-19 and who will refuse to participate in the study - Patients under guardianship, trusteeship or future protection mandate. Statistical methods - Quantitative variables will be described by means (standard deviation) and medians (range) and compared by Student or Mann and Whitney tests. Qualitative variables will be described by numbers and percentages and compared by Chi2 or Fischer exact tests. - Clinical, socio-economic and demographic characteristics of individuals will be described and compared. - The cumulative incidence of seropositivity for SARS-CoV-2 infection by age group (under 60, 60+) and gender (male, female) will be presented. - Changes in the serum antibody titters of specific antibodies to the SARS-CoV-2 virus (increase in titters between the different measurement times) will be described. - Predictors of severe complications will be investigated using logistic regression models. The sample will be divided into two parts: the first part will be used to generate the predictive score for severe complications. The second part) will be used as a validation set for the score. The area under the curve will be used to evaluate the discriminating capacities of the score and the specificity, sensitivity, positive predictive value and negative predictive value of the score will be evaluated. - Prognostic factors for survival will be modelled for all patients using Cox regression. The event studied will be death. Living patients will be censored at the date of discharge from COVID-19. Estimated planning of the Study Beginning of inclusions: July 2020 Estimated recruitment time: 3 months 4 participants follow-up: 4 months data processing: 5 months Total duration of the study: 12 months",2020,-99,N/A,558424.16,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,Gender,,,,Burkina Faso,Epidemiological studies,Disease susceptibility | Prognostic factors for disease severity | Approaches to public health interventions,2020 +C01025,ANRS COV14,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - COVID4P : Analyse de la relation entre pauvreté, pollution, prévention et progression du CoViD-19 au Burkina Faso COVID4P: An investigation of the relationship between poverty, pollution, preventive actions and the progression of CoViD-19 in Burkina Faso","This project investigates the determinants of CoViD-19 transmission in Burkina Faso with a focus on behavioural and environmental factors. We exploit a baseline survey conducted among 800 households in three cities of the Southern Central region three months before the CoViD-19 epidemic to understand how the risk of contracting the disease is affected by an individual's access to information on preventive actions, by the household's budget constraint and by exposure to air pollution (PM2.5). To shed light on this relationship, we will conduct a randomized experiment in which an information treatment aimed at addressing informational market failures will be cross-randomized with unconditional cash transfers designed to incentivize households to adopt preventive actions (regular handwashing, wearing face masks, etc). All sampled households will be re-interviewed pre and post intervention to document disease related learning processes as well as changes in preventive behaviors. Serological tests will be conducted in all adult individuals belonging to the sample after the intervention. Data on individual exposure to particulate matters collected for 550 individuals during the baseline survey at the end of 2019 will be leveraged to explore the relationship between air pollution and the incidence of severe cases of CoVid-19. The panel dataset which will be available at the end of the study will significantly contribute to improving our understanding of the reach of the CoViD-19 epidemic in Burkina Faso and will inform public health and environmental policies aimed at containing future outbreaks of coronavirus.",2020,-99,N/A,444953.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Burkina Faso,Epidemiological studies,Disease susceptibility | Impact/ effectiveness of control measures,2021 +C01026,ANRS COV15,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - COMOKIT : un kit de modélisation à base d'agents pour faciliter l'analyse et la comparaison d'interventions contre l'épidémie de COVID-19 à l'échelle d'une ville COMOKIT: an agent-based spatially explicit modeling kit for analyzing and comparing interventions against the COVID-19 epidemic at the scale of a city,,2020,-99,N/A,186833.92,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Western Pacific,,,,,Viet Nam,Epidemiological studies,Impact/ effectiveness of control measures,2020 +C01027,ANRS COV16,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - Dynamique de l'épidémie à SARS-CoV-2 à Conakry, Guinée (COVEPIGUI) SARS-CoV-2 outbreak dynamics in Conakry, Guinea (COVEPIGUI)","Objectives Primary objective The main objective of the study is to describe the dynamics of the SARS-CoV-2 epidemic in the city of Conakry, represented by the evolution over time of seroprevalence stratified by age group (under 15 years, 15-39 years and 40 years or more). Secondary objectives 1. To estimate the proportion of asymptomatic or pauci-symptomatic cases among participants with positive serology for SARS-CoV-2 infection 2. To estimate seroprevalence overall and by age group in each survey 3. To estimate in each survey the number of confirmed or probable cases of SARS-CoV-2 infection among seropositive participants. 4. To analyze the relationship between demographic and clinical characteristics, possible contact with a confirmed or probable case, and SARS-CoV-2 serostatus. 5. Retrospectively analyse of the sociological conditions of the contamination among serologically confirmed individuals. Methodology: Three repeated general population surveys spaced 6 weeks apart. For each survey, we will use a two-stage random sampling design. The aim is to obtain a representative sample of the population of Conakry. Each survey is independent of the other. Estimated enrolment 1400 individuals per survey The calculation of the sample size is based on the hypothesis of a 10% difference in seroprevalence per age group between the first and second survey, using participants aged 40 years and older because they represent the smallest age group (17.5% of Conakry residents). Assuming an intraclass correlation coefficient (ICC) of 0.10, a participation rate of 90%, an average of one individual aged 40 and over per household visited (on average 6 residents per household in Conakry), with a confidence level α=0.05 and a power of 0.8 (β=0.2), 380 residents aged 40 and over, rounded up to 400 households, or 40 clusters of 10 households, will have to be included in each survey. To balance the groups, individuals under 40 years of age will be invited to participate in the study in only 50% of households. In total, 1400 individuals to participate (400 aged 40 and over + 5 residents under 40 in half of the 400 selected households). Outcomes Primary outcome: The difference in seroprevalence between two surveys Secondary outcomes:  The proportion of symptomatic cases defined as the presence of symptoms of SARS-CoV-2 infection since the beginning of the year among participants with positive SARS-CoV-2 serology : o Fever o Fatigue o Cough (dry) o Rhinitis o Sore throat o Difficulty breathing o Chest pain o Muscle aches and pains o Nausea/Vomiting o Dermatological signs, anosmia, dysgeusia o Asthenia o Anorexia  The proportion of asymptomatic cases among participants with positive CoV-2 SARS serology.  Seroprevalence defined as the proportion of participants by age group with IgG antibodies to SARS-CoV-2.  The number of cases previously confirmed by PCR.  The number of cases previously classified as probable ( https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov).  Contact with a patient with suspected or confirmed SARS-CoV-2 infection.  The proportion of individuals who visited a health care provider for one or more of these symptoms.  Among individuals with a positive serology, the proportion who were diagnosed with CA-MRSA-CoV-2 confirmed infection by PCR, the proportion who were diagnosed with probable infection and the proportion who were undiagnosed. Eligibility Inclusion criteria:  For adult participants (age ≥ 18 years old): Agree to participate in the study and sign the consent prior to any intervention.  For participants under the age of majority (between 10 and 17 years of age): Informed consent signed by at least one parent or legal guardian authorizing the child's participation in the study and the child's written consent to participate in the study.  For minor participants (age < 10 years): Informed consent signed by at least one parent or legal guardian authorizing the child's participation in the study. Non-inclusion criteria:  Inability to comply with study requirements and procedures in the opinion of the investigator;  Inability to consent. Statistical methods The household questionnaire will be used for descriptive analyses on the included population and those who did not participate in the serological survey. For each participant, several dimensions will be considered. The descriptive analyses will be weighted to take into account the probability of selection for cluster sampling and will be presented with a 95% confidence interval. Simple t-test and Pearson chi2 statistics will be used to compare the continuous and categorical descriptive results, respectively. Results will be calculated with the corresponding 95% confidence intervals and stratified by age group and sex. The actual intra-family correlation coefficient will be calculated at the end of the first survey. Serological results will be stratified by age and weighted to take into account the sampling effect. Multivariate logistic models will assess the association between seroprevalence and risk factors in each study. After the first survey, a conventional cross-sectional analysis will be conducted followed by an incremental approach by pooling data from subsequent surveys and introducing a covariate coding for prevalence at each survey. Spatial heterogeneity will be taken into account. The dynamics of the epidemic will be modelled using generalized linear models . In addition, the epidemic diffusion models that will be available, published by other teams, will be applied to the data in order to estimate the diffusion parameters observed in Conakry (cumulative incidence, doubling time, spatial variability of transmission). Estimated planning Study start date: Third quarter 2020 Enrolment period: 4 months Subject participation duration: 1 day Total study duration: 12 months Estimated study completion date: July 2021",2020,-99,N/A,191306.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Guinea,Epidemiological studies,Disease transmission dynamics,2020 +C01028,ANRS COV17,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - Utilisation des outils numériques par les agents de santé communautaire dans la stratégie d'endiguement et d'atténuation de l'épidémie de Covid-19 au Rwanda - une recherche-action Use of digital tools by community health workers in the strategy to contain and mitigate the Covid-19 epidemic in Rwanda - action research,"The coronavirus (Covid-19) pandemic has put the health systems of countries in Europe and the Americas, which are considered to be highly efficient, to the test. Less impacted than the rest of the world, the African continent is also facing the spread of Covid-19. The African continent appears to be the future focus of this epidemic if significant steps are not taken to slow down and contain the epidemic. Rwanda, an East African country, is also affected, with more than a hundred cases diagnosed to date, of which more than 75% are imported cases. Rwanda has a large network of community health workers (CHWs) spread throughout the country whose role is essential in the field of primary health care. The experience of the Ebola epidemic has shown that CHWs played a key role in controlling the epidemic but also highlighted the need to involve CHWs early in the epidemic response to ensure optimal effectiveness. CSAs can be indispensable actors in this fight. The use of digital tools, which are being increasingly used, particularly in Rwanda, as a communication tool within the health system with its CHWs can provide important added value to these actors to implement an effective strategy against the Covid-19 epidemic. The objective of this action-research project is to develop, implement and evaluate the feasibility and contribution of connected tools for the detection and monitoring of Covid-19 cases and contacts by CHWs in a strategy to contain and mitigate the Covid-19 epidemic in Rwanda. The intervention will be based on an application providing access to a website that will offer hetero-questionnaire assessment for any person suspected of Covid-19. The questionnaire will focus on symptoms suggestive of Covid-19 (including fever, myalgia, anosmia and agueusia), signs of severity (shortness of breath, inability to eat or drink mainly) and co-morbidities. Depending on the situation, the patient will be referred to simple surveillance by the CSA with containment modalities defined by the Rwandan health authorities, or will be referred to a health centre for paramedical evaluation, or to the district hospital in case of signs of severity. Contacts will be identified by the CHWs with assistance in identification through the website following the questionnaire in case of symptoms in favour of a Covid-19. CHWs will monitor contacts by administering the same hetero-questionnaire to monitor the occurrence of symptoms. The project will train CHWs (n=400) in 2 districts (urban and rural) already equipped with smartphones. Judgement criteria will include the proportion of CHWs adhering to the project, the perception of the CHWs on the role and satisfaction of the populations, the number of questionnaires completed and possible cases detected, the number of people referred to a health centre or district hospital and the number of contacts identified, followed by the CHWs and the number of cases identified among these contacts. This pilot project will be subject to a rapid evaluation (at 1 and 3 months) in order to propose its extension to the whole country in case of favourable feasibility results (process indicators).",2020,-99,N/A,141028.16,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,Digital Health,,,,Rwanda,Clinical characterisation and management,"Supportive care, processes of care and management | Medicines, vaccines & other technologies | Health workforce",2020 +C01029,ANRS COV18,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - Prévalence de l'infection à COVID-19 chez des patients VIH séropositifs à l'étude pour la tuberculose dans le contexte de l'étude FujiLAM Prevalence of COVID-19 infection in HIV-positive patients being investigated for tuberculosis in the context of the Fujilam study,"Background The outbreak of a novel coronavirus (SARS-CoV-2), characterized as a pandemic by the WHO on 11 March 2020, has disrupted the health systems worldwide. Most of the cases of coronavirus disease (COVID-19) have been reported in the North hemisphere of the globe, but the epidemic has taken hold in the South including African countries. People with underlying comorbidities and suppressed immune systems are particularly vulnerable to coronavirus disease. There is a lack of information on prevalence and severity of this emerging disease among HIV patients with TB. This study proposes to incorporate COVID-19 testing and follow-up into an existing multi-country study of novel tuberculosis diagnostics among HIV-positive patients at high risk. The objectives of this study are to assess the prevalence and severity of COVID-19 among HIV positive patients. Methods Prospective observational study nested in the FujiLAM study. Covid-19 testing will be done in 2 of the 4 FujiLAM study sites, in Mbarara, Uganda and in Homa Bay, Kenya. The parent study includes two groups of ambulatory adult HIV-positive patients at high risk of TB: Ambulatory HIV-positive patients with symptoms of TB (Group 1) and ambulatory HIV-positive patients with advanced HIV disease and no symptoms of TB (Group 2). Patients included in the study will be seen by a clinician, who will conduct a clinical exam and will request COVID-19 and TB investigations. Patients will be followed for 6 months. Patients diagnosed with Covid-19 will be managed as per the national recommendations. The main study endpoints will be the proportion of HIV-positive patients diagnosed with COVID-19 among those with symptoms of TB and the proportion of HIV-positive patients with past contact with SARS-CoV-2 measured through the presence of antibodies among those with symptoms of TB and among those with advanced HIV disease and no symptoms of TB. A total of 500 HIV-positive patients with symptoms of TB and 780 patients with advanced HIV disease and no symptoms of TB are expected to be included in Kenya and Uganda. Timelines The study is expected to start in August 2020. Patients recruitment is expected to take 6 months and patients will be followed for 6 months.",2020,-99,N/A,185920,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Kenya | Uganda,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2020 +C01030,ANRS COV19,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - NOSOCOVID: Prévention de la transmission du COV-19 dans les établissements de santé égyptiens NOSOCOVID : Preventing the spread of COVID-19 in Egyptian healthcare settings,"Egypt had the first reported confirmed case of COVID-19 on the African continent on Feb 14, 2020. Local transmission has been confirmed since, and as of Apr 10, 2020, Egypt ranked among the countries the most affected in Africa with 1,699 confirmed cases. The Egyptian health authorities' response was one of the first to be implemented on the continent. Currently, the healthcare response relies on several quarantine hospitals devoted for COVID-19 patients only. This strategy could be completed with a broader mobilization of general hospitals in case of COVID-19 patients overload. In this context, healthcare institutions are facing major challenges. First, the community spread is leading to a large demand in available beds and to a saturation in hospitals dedicated to COVID-19 patients, particularly in intensive care units. Second, the outbreak, its managements, and the fact that healthcare workers are particularly exposed to the virus are causing a large-scale disorganization of the entire healthcare system. Third, healthcare settings have been shown to be hotspots of transmission of coronaviruses, notably due to the high density of contacts. Mathematical modelling has become a standard to analyse the spread of infectious diseases. It has provided a theoretical framework for understanding complex transmission dynamics within healthcare settings and a quantitative approach to estimating the impact of various infection control strategies and their combined effects. This approach has already been widely developed to understand, anticipate and assess possibilities for controlling the current COVID-19 epidemic in the community. However, no model has yet been specifically proposed to assess control measures in healthcare settings. Moreover, models for nosocomial transmission in healthcare settings for various pathogens have gathered important interest in high-income countries. However, there has been a scarcity of research efforts to model pathogen spread in healthcare settings in low- and middle-income countries. The objective of this project is to address the risk associated with SARS-Cov-2 nosocomial transmission and support its control in an Egyptian healthcare setting. More specifically, the project will rely on the adaptation of an existing mathematical model to simulate different healthcare organization and control strategies. The model will be calibrated in order to reproduce the SARS-Cov-2 circulation in an Egyptian quarantine hospital (15th of May Hospital, Cairo). Then, we will evaluate various control strategies, including those considered by local health authorities, in terms of risk of COVID-19 acquisition by healthcare workers. In a second step, the model will reproduce the virus circulation in a general hospital with a dedicated section for COVID-19 management, and strategies will be evaluated in terms of risk of COVID-19 acquisition by patients and healthcare workers. Results of this project will provide insight for the control of nosocomial dissemination of SARS-Cov-2 in Egypt. Results may also be informative at a broader scale, on the African and above. Keywords: mathematical modelling, transmission, healthcare setting, control strategies, healthcare workers",2020,-99,N/A,97558.72,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Egypt,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | IPC in health care settings,2020 +C01031,ANRS COV20,Epidémiolgie - Santé Publique (Epidemiology - Public Health) - LACOVISS : Investigation épidémiologique du SARS-CoV-2 au Laos par une approche One-Health LACOVISS: One-Health approach in Epidemiological investigation of SARS-CoV-2 in Laos,"The Respiratory infection COVID-19, due to a new coronavirus, SARS-CoV2, appeared in December 2019 in several people who attended the wildlife market in Wuhan, Hubei Province, China. While COVID-19 has spread to nearly 200 countries and caused two millions infections, Lao PDR detected its first confirmed case very recently, on March 20, three months after the start of the outbreak in China. As of April 12th, 2020, Lao PDR has only recorded 18 confirmed cases, a very low number compared to other countries around the world. However, several key factors suggest that Lao PDR could be much more affected by COVID-19 because of the following reasons: (i) The multiple and massive trans-border movements between Lao PDR and China. (ii) The similar biogeographical and socio-ecological characteristics with South-Western China. (iii) The detection of a high diversity of Betacoronavirus sequences in several species of bats in Lao PDR. (iv) The numerous markets selling high volumes of local wildlife including bats and pangolins. LACOVISS project aim at investigating, using a ONE-HEALTH approach, this unexpected epidemiological pattern of SARS-CoV-2 in Lao PDR by bringing together an interdisciplinary team of experts in the field from IRD, the University of Caen, the Center of Infectiology Lao-Christophe Mérieux (CILM) and the National animal Health Laboratory (NAHL) in Vientiane. We will focus on a community-based cohort of 1092 households, including 5400 study participants, followed-up between March 2015 and February 2019 for influenza-like illness investigation and causative agents detection (LACORIS project), located in the Vientiane metropolitan area. We will follow up the COVID-19 progression in Lao PDR, and track SARS-CoV-2, retrospectively and prospectively, in all potential actors in SARS-CoV-2 circulation, including humans, domestic animals, and wildlife. The LACOVISS project will undoubtedly bring new insight in SARS-Cov-2 and SARS-CoV-like circulation in Lao PDR as well as valuable information on the natural history of COVID-19, and on the modalities of the spillover into humans, which are still largely unknown.",2020,-99,N/A,365625.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,South-East Asia,,,,,Lao People's Democratic Republic,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics,2021 +C01032,ANRS COV21,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - Evaluation d'une stratégie de dépistage du SARS-CoV-2 en routine chez le personnel et les femmes accouchant à la maternité du CHU Yalgado Ouédraogo, Ouagadougou, Burkina Faso : acceptabilité, prévalence et devenir du couple mère-enfant à six semaines. Assessment of a routine screening strategy of SARS-CoV-2 in health professionals and delivering women at the maternity hospital of Y. Ouedraogo Hospital, Ouagadougou, Burkina Faso: acceptability, prevalence and six-week outcomes of the mother-child pair.","Burkina Faso was one of the first countries in West African to report cases of SARS-CoV-2 infection. As the epidemic becomes more generalized, healthcare workers and pregnant women are being affected as much as the rest of the population. Knowledge on the coronavirus is limited in Africa, and pregnant women are a useful sentinel population in epidemic surveillance. In this context, we find a unique opportunity to implement and evaluate operational research in a maternity ward, reinforcing the protection of healthcare workers, as a priority, and evaluating a routine screening strategy for SARS-CoV-2 infections in healthcare workers, and parturient women. Objective: Main objective: To implement and evaluate a routine screening strategy for SARS-CoV-2 infection with triage of healthcare workers and parturient women at the Yalgado Ouédraogo University Hospital maternity ward, in Ouagadougou in Burkina Faso, - to measure the epidemiological indicators (prevalence and incidence) of the infection and its impact on short-term mother-infant health outcomes (morbi-mortality, birth and pregnancy outcomes and mother-to-child transmissions). Intervention : This intervention will take place over a 6-month period and allow building and exhaustive prospective cohort with 6 weeks of follow-up of mother-infant pairs Site : Yalgado Ouédraogo University Hospital maternity ward, Ouagadougou, Burkina Faso Study design: Cross-sectional study including a SARS-CoV-2 diagnostic test by rt-PCR to all healthcare workers, and to parturient women presenting symptoms in line with probable COVID-19 cases, followed by an observational prospective cohort comprised of delivering women at the Yalgado Ouédraogo University Hospital maternity ward and followed-up with their newborn until 6 weeks post-partum, and according to their exposure to SARS-CoV-2. Inclusion criteria: All healthcare workers working in Yalgado Ouédraogo University Hospital maternity ward at the time of implementation of the study, who give informed consent; all parturient women in the maternity ward from July 1st to December 31st 2020, who give informed consent and live in Ouagadougou with their newborn. Evaluation criteria : -Acceptability of SARS-CoV-2 screening at birth - Prevalence of active SARS-CoV-2 infection, and past infection with acquired immunity at birth - Morbidity, maternal mortality and immediate and 6-week post-partum complications - Birth outcome complications: low birth weight, prematurity, microcephaly, stillbirths, birth defects - Early and late-run neonatal mortality - Estimate of SARS-CoV-2 mother-to-child-transmission at birth at 6-week postnatal - SARS-CoV-2 infection and its consequences, preventive measures and screening knowledge, attitude and practice and perceptions - Acceptability of SARS-CoV-2 diagnosis by RT-PCR among healthcare workers in the maternity and pediatric wards and associated factors. Size: 200 healthcare workers and 3150 mother-infants pairs at birth, of whom 1225 possible cases requiring diagnosis",2020,-99,N/A,590815.68,Human Populations,Black,Adults (18 and older),Unspecified,Pregnant women,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Burkina Faso,Epidemiological studies | Clinical characterisation and management | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Post acute and long term health consequences | IPC in health care settings,2021 +C01033,ANRS COV22,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - Évaluation de l'impact des mesures de lutte contre l'épidémie de COVID-19 sur les comportements à risque pour le VIH et le VHC et sur l'accès à la prévention et aux soins pour les usagers de drogues injectables à Hai Phong, Vietnam (DRIVE-COVID) DRug use & Infections in ViEtnam: Evaluating the impact of lockdown measures to control the COVID-19 epidemic on HIV and HCV risk behaviours and access to prevention and care for people who inject drugs in Hai Phong, Vietnam (DRIVE-COVID)","Primary objective: To assess changes in HIV and HCV risk behaviours and in access to prevention and care for people who inject drugs (PWID) in Hai Phong city, following the implementation of restrictive and lockdown measures taken to control the COVID-19 epidemic in Vietnam. More specifically, the study will assess changes for PWID in terms of: (i) risk behaviours for HIV and HCV infections related to drug use; (ii) access and adherence to opioid substitution therapy (OST); (iii) access and adherence to antiretroviral treatment (ART) for those HIV-infected; (iv) access to harm reduction materials. Secondary Objectives: - To assess changes for PWID in terms of: (i) access to drugs and patterns of drug use; (ii) risk behaviours related to sex practices; (iii) access to counselling and support from health care staff, peer educators and members of community-based organizations (CBO); (iv) quality of life; (v) mental health, with a focus on suicidal risk, depression, psychotic syndrome and anxiety; (vi) individual social and economic situation; (vii) occurrence of administrative events (including incarceration); (viii) occurrence of life-threatening events (including overdose, suicide) and episodes of violence; (ix) access and adherence to psychiatric treatment for patients enrolled in the ANRS 12410 DRIVE-MIND study. We will also model the impact in terms of excess HIV and HCV infections and relative increase in HIV and HCV incidence resulting from changes due to the lockdown compared to if pre-lockdown behaviours and access to interventions had remained. Methodology Study design: before-after design approach, supplemented by a qualitative component and mathematical modelling. The measurement of study outcomes during the 'before' (restriction) period will be drawn from the latest visit of either NIDA RO1DA041978/ANRS 12353 DRIVE, ANRS 12380 DRIVE-C or ANRS 12410 DRIVE-MIND studies. The same outcomes will be measured during the 'after' (restriction) period through a cross-sectional survey, conducted after the lifting of restrictive measures: during a specific follow-up visit organized for DRIVE participants; during the 'End of study' visit for DRIVE-C participants as planned in the DRIVE-C study; during the month-18 follow-up visit for DRIVE-MIND participants as planned in the DRIVE-MIND study. Potential changes that occurred specifically during the restriction period will be assessed retrospectively during this survey, that will also be complemented by data collection in treatment clinics and from CBO. The qualitative component will include 2 phases: (i) a preliminary work based on focus group discussions (FGD) with CBO members, and (ii) in-depth interviews with participants during the study data collection period. The modelling component will use a HIV and HCV transmission model being developed for the ANRS 12380 DRIVE-C study, utilising new data collected by DRIVE-COVID to parameterise how lockdown has changed behaviours and intervention outcomes. - Estimated enrolment: (i) cross-sectional survey: 930 participants; (ii) qualitative component: 20-30 participants. Primary endpoint: The changes in HIV and HCV risk behaviours and in access to prevention and care for PWID will be assessed through four main indicators, compared before and after the period of COVID-19-related restrictive measures: (i) self-reported frequency of sharing needles/syringes and water/Novocain; (ii) proportion of PWID receiving OST and adherence to OST (urine testing, self-assessment and medical file); (iii) proportion of HIV-infected PWID receiving ART and adherence to ART (HIV viral load testing for all HIV-infected, self-assessment and medical file); (iv) self-reported number of sterile needles/syringes accessed per month. Inclusion criteria: - The following participants of the ongoing NIDA ROIDA041978/ANRS 12353 DRIVE, ANRS 12380 DRIVE-C and/or ANRS 12410 DRIVE-MIND studies will be enrolled: - DRIVE participants who were enrolled in the 4th respondent-driven sampling survey of DRIVE (RDS4) and agreed in the DRIVE informed consent form to be contacted again for a future study; - DRIVE-C participants still on follow-up and having their DRIVE-C 'End of study' visit planned during the 'after' period; - DRIVE-MIND participants still on follow-up. Non-inclusion criteria: inability to understand the study or unwillingness to sign the consent form for this study after receiving information. Intervention: Cross-sectional survey: a standardized questionnaire will be applied and biological testing (blood, urine) will be performed to collect the measurements of study outcomes during different follow-up visits for DRIVE, DRIVE-C and DRIVE-MIND participants, either on community study sites or at HCV study clinics. Those will be complemented by data collection in OST and ART clinics, as well as from CBO. Qualitative component: focus group discussions with CBO members and in-depth interviews with participants will be conducted on community study sites. Study agenda: - Study preparation: May - June 2020 (2 months) - Data collection: July - September 2020 (3 months) - Data analysis: October - December 2020 (3 months) - Overall duration of the study: 8 months.",2020,-99,N/A,100434.88,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Western Pacific,,,,,Viet Nam,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01034,ANRS COV23,"Epidémiolgie - Santé Publique (Epidemiology - Public Health) - COVICAM, Investigation sero-epidemiologique des contacts et des communautés entourant les cas confirmes d'infection a SARS-CoV-2 au Cambodge COVICAM, Sero-epidemiologic investigation among contacts and communities of SARS-CoV- 2- laboratory-confirmed cases in Cambodia",,2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Western Pacific,,,,,Cambodia,Epidemiological studies,Disease transmission dynamics, +C01035,ANRS COV24,SHS (Humanities and Social Sciences) - MEDIACAM - Tracking trust and suspicion: Analyzing social media to sharpen COVID-19 public health responses in Cameroon,"How to promote acceptance, uptake, and adherence to public health measures for COVID-19 prevention and control? What are the most effective ways to address the underlying drivers of fear, anxieties, rumours, stigma regarding, and how to improve public knowledge, awareness, and trust during the response? In a context characterized by severe political frictions exacerbated by low level of trust in political leaders, this project provides an innovative approach to help fill these information gaps and assist both public health measures and refining media and communications efforts. This project will focus on issues of trust and its relationship with political authority in Cameroon. It will use a comprehensive approach drawing insights from anthropology (dynamics of blame and heroization), political sociology (how State-society relations are built and challenged), science studies (foundations of scientific authority and dynamics of controversies) and digital social science (uses of social media by lay public and activists). A special attention will be devoted to the plurality of voices on both scientific and policy issues and public reactions to contradictory information. A balanced combination of computational social science (network analysis, computational linguistics) physical ethnography, and a qualitative approach grounded in the anthropology of the web offers the perfect perspective to achieve our goals. Results from this research will directly inform policymaking during the pandemic and improve knowledge and awareness on the most effective ways to address the underlying drivers of fear, anxieties, rumours and stigma regarding COVID-19. Objective 1: Explore accusatory dynamics associated with COVID-19 by analysing the main figures of blame and heroes present in Twitter conversations in French, and in mainstream Anglophone media websites. Objective 2: Examine the links between digital and traditional media in Cameroon by studying conversations linked to news coverage of the epidemic, including comments posted in response to online articles, conversations posted on online forums, and sites and blogs directly linked from these comments. Objective 3: Inform policy-making and improve public knowledge on the most effective ways to address the underlying drivers of fear, anxieties and rumours by identifying the limits of ""open science"" in times of epidemics and the links between the use of scientific knowledge by governments and assessment on their ""democratic"" nature.",2020,-99,N/A,215243.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa | Europe,,,,,Cameroon | France,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C01036,ANRS COV25,"SHS (Humanities and Social Sciences) - Négocier ses mouvements et adapter son quotidien. Recueil participatif << sur le vif >> des expériences camerounaises face au risque sanitaire, par l'utilisation de l'outil numérique Negotiate your movements and adapt your daily life. Participatory collection ""on the spot"" of Cameroonian experiences facing health risk through the use of the digital tool","In the current Covid-19 pandemic, disease perception, etiology and the understanding of spreading risks influence the way each person reacts toward the pandemic and its associated risks. In Cameroon, recent research by anthropologists ""on the spot"" shows that the population are comparing Covid-19 to malaria and dengue fever, and see the disease as a fever transmitted by external agents, such as mosquitos. Our project research objective is to document, collect and understand, through a participatory research approach, Cameroon populations' experiences in a pandemic period regarding the evolution of the situation (state of emergency, reduction of individual freedoms, partial or total lockdown, end of lockdown, etc.). The methodology used in this project is innovative and ses digital tools to collect data from participants. A smartphone application will be used to complement qualitative surveys using semi-structured interviews. Daily and weekly variables will be measured to collect individual and social habits and practices, through a several months period. We want to understand how individual mobility is negotiated in a context of health risk as well as the forms of socialization which appear or persist.",2020,-99,N/A,104016.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa | Europe,,,,,Cameroon | France,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C01037,ANRS COV26,"SHS (Humanities and Social Sciences) - CORAFMOB : Mobilisations communautaires et enjeux socio-sanitaires face au COVID-19 (Sénégal, Burkina Faso) CORAFMOB : Community mobilizations and socio-sanitary challenges facing COVID-19 (Senegal, Burkina Faso)","BACKGROUND During previous epidemics (HIV, Ebola), the community sector has played a very important role, in particular through Community Based Organizations (CBOs), in various fields: care, investigation and follow-up of suspected cases, management of patients, advocacy, fight against stigma and for human rights, support for marginalized and vulnerable populations, etc. Community actors, CBO members or health workers (volunteers, mediators or contract workers) have been on the front line with AIDS and Ebola patients. However, their place in response mechanisms to the COVID-19 pandemic at global (WHO), regional (Africa CDC) or national level seems more limited. Since the first cases, different community mobilizations have appeared in Senegal (where the initiative generally comes from the State) and in Burkina Faso (where the CBOs have carried out numerous health initiatives), these countries also differentiating themselves by their experience of the Ebola epidemic. Community mobilizations against COVID-19 must be documented and analyzed to understand their potential contribution (and their limits) to all the pillars of COVID19 response. OBJECTIVES The main objective of this operational research project is to strengthen the response against COVID-19 by documenting and analyzing community mobilizations and their socio-health challenges in Senegal and Burkina Faso. The secondary objectives are to describe and compare:  Individual and collective community reconfigurations linked to COVID-19  The impact of COVID-19 and response measures on community actors (agents and organizations) and their adaptation  The models of mobilization and areas of involvement of CBOs, their achievements and limits  The interventions of community actors in / with the healthcare system METHOD After a situational analysis, the qualitative approach will combine interviews, observations and document analyzes with community actors, CBOs, health actors and people affected by COVID-19. The analysis will compare the role given to CBOs in the COVID response and in the HIV or Ebola responses and the various experiences, professional and associative cultures and memories engaged in the COVID response. RESULTS Expected analytic results include an evidence-based description of achievements and limits of community organizations and health workers' contribution in COVID-19 response and of their background. Applied results include indications and recommendations for better community engagement and democracy in managing community health issues involved in the COVID-19 pandemic.",2020,-99,N/A,151773.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Burkina Faso | Senegal,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2020 +C01038,ANRS COV27,SHS (Humanities and Social Sciences) - Normes sociales à l'épreuve des mesures de riposte contre l'épidémie du COVID-19 : Une étude socio-anthropologique du vécu quotidien des populations de Bobo-Dioulasso (Burkina Faso) Social norms tested by the measures of response to the COVID-19 epidemic: A socio-anthropological study of the daily experience of the populations of Bobo-Dioulasso (Burkina Faso),"This research project is a socio-anthropological study on social norms that test the measures taken in the response to the COVID19 epidemic in Burkina Faso. He is mainly interested in the experiences of the social actors of the city of Bobo-Dioulasso by seeking to document and analyze their daily practices and their perceptions of barrier measures in the context of control and prevention of this epidemic. To achieve this main research objective, this study is based on a mixed approach that includes both a qualitative and quantitative approach. The various empirical work will take place in the Municipality of Bobo-Dioulasso and the data will be collected from four types of social actors: traders and other informal actors; religious and customary leaders; health workers; and the general population. The main expected results of this study are related to the documentation of knowledge capital and the assessment of the level of understanding of social actors of the Municipality of Bobo-Dioulasso, compared to the measures barriers of prevention of COVID-19; the identification of existing social norms of behaviour in relation to barrier measures; and above all the analysis of the given meanings, from the point of view of these actors in relation to their past experiences and daily experiences.",2020,-99,N/A,226152.64,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Burkina Faso,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C01039,ANRS COV28,SHS (Humanities and Social Sciences) - Tester le coronavirus au Brésil : politiques de santé et capacité diagnostic dans un pays du Sud Testing coronavirus in Brazil: healthcare policy and diagnostic capacity in the South,"This research project aims to investigate the different aspects (political, economic, industrial, historical and geographical) related to the implementation of SARS-COV-2 (covid-19) testing in Brazil. It addresses special attention to three aspects: creation of diagnostic capacity in the absence of a national political coordination; intellectual property management and diagnostic companies' business models in times of a pandemic; and regulation of both tests and patients' health data.It will employ a methodological approach that suits its dual concern of following real time response to coronavirus in Brazil to data collection that is adapted to a pandemic that requires restriction in circulation of populations. Our methods will be two-fold: document analysis and expert interviews. We will complement data with in presence techniques, in particular participation observation, interviews in person and visits to industrial sites and clinical facilities.These different research activities will provide a number of different outcomes that will enable a comprehension of the different aspects interfering with the implementation of testing technologies and infrastructure in Brazil. These outcomes will also have use for crafting public policies to improve the testing policies for coronavirus and other infectious diseases epidemics in the country. Moreover, these results will be available to non-professional actors serving to promote debate on this crucial issue and potentially engage new actors in the discussion of testing policies, such as patients groups and other civil society movements.",2020,-99,N/A,53460.96,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Americas,,,,,Brazil,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience",Diagnostics | Policy research and interventions,2020 +C01040,ANRS COV29,SHS (Humanities and Social Sciences) - Mesurer la vulnérabilité des entreprises des pays en développement au choc du Covid-19 Measuring the vulnerability of developing countries' firms to Covid-19,"The objective of this research project is to develop a synthetic indicator to measure the effects of the COVID-19 shock and the lockdown of a large part of the world on enterprises in developing countries.The aim is to provide public decision-makers with means to identify the most vulnerable firms and those with the greatest ability to impact the rest of the economy. This information will make it possible to better target public aid, given the scarcity of resources in most of these countries. The project will also assess the structural consequences of the COVID-19 pandemic on the economies of developing countries, particularly in terms of intersectoral reallocation. The approach developed in this research is tested using Tunisian data, then the analysis is extended to other African and Asian countries for which business survey data are available. The objective of this research project is to develop a synthetic indicator to measure the effects of the COVID-19 shock and in particular the containment of a large part of the world on firms in developing countries. As a first step, we aim to give public policy makers the means to identify the most vulnerable firms and those with the greatest ability to influence the rest of the economy. This will help to better target public aid, given the scarcity of resources in most of these countries. Due to the non-existence of unemployment benefits and limited social protection, the effects on companies are almost entirely transmitted to households. In a second step, we aim to assess the structural consequences of the COVID- 19 pandemic on the economies of developing countries, particularly in terms of intersectoral reallocation. The approach developed in this research is tested using Tunisian data, and the analysis is then extended to other African countries for which we will have data from company surveys. The originality of our approach consists in developing a multidimensional index of firms' vulnerability to the COVID-19 shock and in identifying the determining dimensions and the weight of each factor. In addition, we will examine the effects of CPVID-19 on a sectoral basis, which will allow us to highlight the long-term structural implications (recomposition of the economy). On the other hand, part of our analysis takes Tunisia, an emerging North African country, as a case study. Finally, our originality also lies in the fact that we will construct our indicator from standardised data, which will allow us to apply our analysis of the vulnerability of enterprises to COVID-19 to other developing countries. We will be interested in countries with similar levels of development to Tunisia, in South Asia for example, as well as countries or less developed countries in Sub-Saharan Africa. The developed index will take into account supply-side effects due to lack of access to firms, markets and inputs. The first effects depend on the propensity to telework in the sector in question and the investment of firms in digitisation of their operations and other logistical capacities for supply and delivery. A key factor in the difficulties of upstream and downstream access is integration into global value chains. The capacity of business continuity plans depends on access to cash, especially if heavy investment is required to adapt or redirect the business (e.g. a clothing factory that starts producing masks or a hotel that turns into a clinic). An index measuring the feasibility of teleworking by professions will be used to assess the impact of containment on businesses, on the demand side. The global bottlenecks affect not only the supply side but also the demand side of Tunisian companies participating in global supply chains. To separate the effect of the export demand shock from other effects such as those of the supply shock or the fall in domestic demand, we exploit the change in the volume of imports of 6-digit products of the Harmonized System nomenclature code of destination countries. Monthly exports by destination and by product category supplied by the customs of destination countries allow us to take into account the recent effects of the health crisis. The methodology consists of constructing an index based on business surveys, econometric analysis, input-output matrices and possibly factor analysis techniques to check the robustness of the index to the method of aggregating its components.",2020,-99,N/A,69888,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Tunisia,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01041,ANRS COV30,"SHS (Humanities and Social Sciences) - COVID-19 et VIH. Mobilisation, reconfiguration des soins et affects des acteurs du VIH/sida face au COVID-19 à Maurice et Madagascar : patients, soignants, et acteurs associatifs. COVID-19 and HIV. Mobilization, reconfiguration of care and affects of HIV/AIDS actors in the face of COVID-19 in Mauritius and Madagascar: patients, health care and NGO-workers.","The Indian Ocean has been hit by the Covid-19 epidemic since mid-March 2020. Mauritius and Madagascar, two neighbouring countries, experience contrasting situations from the point of view of their socio-economic development, of their health system and the delivery of healthcare services. However, People Living with HIV (PLHIV) in these two countries face common difficulties in maintaining medical follow-up and antiretroviral treatment, due to the persistent stigmatization of PLHIV. The Covid-19 epidemic has led states to take exceptional measures, in particular the mobilization of health professionals and services to care for people with the disease, and the adoption of measures to limit the spread of the virus (containment, curfew, social distancing ...). Such a context is likely to jeopardise the continuum of care for people suffering from chronic diseases, as well as the organisation of health care and the activities of the teams responsible for their psychological and social support. In this research, we are particularly interested in the actors of HIV / AIDS: PLHIV, healthcare and NGO-workers. Objectives: The general objective of this project is twofold: 1/ It aims to produce knowledge concerning the effects of the Covid-19 health crisis on HIV stakeholders: PLHIV, care institutions and community associations, during and after the Covid-19 crisis, in Mauritius and Madagascar. This includes documenting in particular :  the effects of the Covid-19 health crisis on the care pathways and retention of care for PLHIV, in particular documenting the effects and management of ARV supply disruptions;  the mobilization of health workers and associations in the face of Covid-19: how is their expertise in the field of HIV mobilized in the context of Covid-19? What are the effects of these mobilizations on practices, interactions with users, with the public, between colleagues (HIV associations, social and humanitarian associations, healthcare workers and institutions), and the affects?  the way in which these mobilizations lead to a reconfiguration of care spaces and activities. 2/ The aim of this project is to transfer knowledge to decision-makers, health and association players in order to guide national strategies in terms of maintaining care for people living with HIV in an epidemic context and improving working conditions professionals involved, to support public health policies and respond adequately to needs. Methodology In each country, we will carry out individual semi-structured interviews with: - 30 PLHIV: 15 men and 15 women, of various age groups and social categories, including PLHIV who have had Covid-19 (or think they have had it) - 15 health professionals involved in the care of PLHIV - 20 members of PLHIV community organisation. The study protocol, interview templates, information notices and informed consent forms will be the same in both countries, which will allow for comparative analyses. Expected benefits In order to maximize the usefulness and use of the results by non-for-profit organisations caring for PLHIV, health professionals and decision-makers on HIV in Mauritius and Madagascar, a ""knowledge transfer"" component will be implemented. Through this approach, we will be able to ensure that the results of the research will help guide national strategies in terms of maintaining care for PLHIV in an epidemic context, support public health policies and respond more adequately to needs. The ""knowledge transfer"" will be developed within the framework of this project, in order to reduce the gap between the scientific knowledge produced and its use by associations, and decision makers in matters of HIV. The deliverables for this ""knowledge transfer"" objective will consist of two policy briefs, one for each country, developed with the support of an ""knowledge transfer"" expert who will accompany the team throughout the project.",2020,-99,N/A,154206.08,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Madagascar | Mauritius,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +C01042,ANRS COV31,SHS (Humanities and Social Sciences) - COBra :- Effects of COVID-19 outbreak on the sexual and mental health of adolescent and adult men who have sex with men and transgender women participating in two PrEP cohorts studies in Brazil,"COVID-19 is a global public health emergency. In contexts where official information about the pandemic is inconsistent, like Brazil, public understanding of COVID-19 may be hindered. Besides being a health emergency initself, the COVID-19 outbreak can have detrimental effects in other health issues, such as sexual and mental health. Limitations on healthcare provision during the outbreak along with displacement restrictions due to quarantine may affect HIV and STIs prevention, impacting access to preventive supplies and leading to changes in sexual and preventive behaviors. Among men who have sex with men (MSM) and transgender women (TGW), in particular, quarantine may affect mental health and increase domestic violence related to homophobia and transphobia. In this study, we aim to investigate the effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult MSM and TGW participating in two HIV pre-exposure prophylaxis (PrEP) cohorts in Brazil, with an emphasis on HIV and STIs, both during and after the quarantine period. The study uses a mixed-method approach and is nested in two cohort studies ongoing in Brazil: PrEP15-19 and Combina, which offer PrEP and other HIV combination prevention methods to adolescents and adults, respectively. Follow-up procedures include quarterly visits to the healthcare facilities for medical consultations, counseling and HIV and STI testing. During the quarantine period, most consultations and procedures have been adapted to use videoconference and texting, and PrEP and HIV self-testing (HIVST) are mailed to participants. All PrEP 15-19 and Combina participants will be invited to respond to an online questionnaire. Baseline participants will be recruited between the fifth and sixth week of quarantine in each city. Follow-up will occur in twotime points: participant's next visit to the studies' clinics and one year after the baseline. HIV infection at baseline will be evaluated by an HIVST and the following blood tests will be done during regular follow-up procedures. Baseline data collection will cover information on: socioeconomic, COVID-19 quarantine measures, sexual health, and mental health issues. After quarantine, use of HIV/STI prevention methods, use of PrEP, HIV infection, and symptoms of depression will be evaluated, and the ques-COVID-19 baseline will be applied again. Sample size was estimated on the assumption of 6% of change in sexual behavior after the quarantine (condomless sex in last intercourse or sex without use of PrEP/PEP), power of 80% and a significance level of 95%, thus totaling 426 participants. Multivariate logistic regression will be used to estimate associations between outcome variables and predictor variables, with adjusted odds ratio. The qualitative component will investigate participants' social representation of COVID-19 pandemic and understanding of protection measures, their management of self-care during and after quarantine, and the effects of the COVID-19 outbreak on their STI/HIV prevention behaviors. In accordance with ethical research standards, around 50 in-depth interviews through video calls or interactive voice response will be conducted with adolescents and adults. Other data collection strategies include practices integrated into the social lives of participants, namely daily recorded narratives using WhatsApp, and photographs that represent their daily lives during the pandemic. COBra is a collaboration between the coordination teams of PrEP15-19 and Combina cohorts based at public universities in Brazil, and GRePS Laboratory, based at Université Lumière Lyon 2, which currently runs an investigation on the social representations of COVID-19 and its impacts on the adaptation to quarantine.",2020,-99,N/A,155355.2,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Americas,,,,,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01043,ANRS COV32,"SHS (Humanities and Social Sciences) - COVID-19, Conditions de vie et comportements : Enquête longitudinale dans le Sénégal rural (CO3ELSER) COVID-19, living conditions and behaviours: longitudinal survey in rural Senegal","Our project consists of carrying out a longitudinal telephone survey in the rural Health and Demographic surveillance system (HDSS) of Niakhar, 155 km from Dakar, in three rounds spaced between 15 days to one month. In the first round, the objective is to obtain the participation agreement of 500 heads of household in the area. Each of them will answer a 5-10 minute questionnaire to determine the current size of the household, and its possible recent increase following COVID19 outbreak. The heads of household will also answer a few questions aimed at assessing their perceptions of the possible difficulties they are dealing with inside their household in connection with the recent increase in the size caused by the COVID 19 (food, access to concession equipment, etc.). The answers given will then be matched with the data from the Health and Demographic surveillance system , so that we will have access to detailed and up-to-date information, particularly concerning household equipment, size , or the level of economic and agro-pastoral wealth . The following topics: preventive behavior with regard to COVID-19, risk perception and risk denial will be assed and analyzed against data from Niakhar DSS (age, level of education, marital status, religious denomination, the area comprising approximately 74% of Muslims and 18% of Catholics, etc.). This survey will then be repeated with the same people (the head of household and the two adults), during two other rounds spaced between two weeks to one month, depending on the course of the epidemic in Senegal: the objective here is to capture behaviors, perceptions and beliefs at distinct phases of the epidemic. Oral consent will be requested from participants given the context and situation relating to COVID19. A yes or no answer to participate will be documented in the questionnaire which will be accompanied by an information note. Senegalese law on the protection of personal data will be respected and participation will be voluntary. The project is sponsored by ANRS and its duration is from July 2020 to July 2021",2020,-99,N/A,147042.56,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Africa,,,,,Senegal,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Other secondary impacts,2020 +C01060,AH/V006819/1,COVID-19: The ethical Exit Strategy: the path from relaxing measures to vaccination,"The focus around the Covid19 outbreak is at the moment mostly on the lockdown measures. However, the lockdown implies a societal, economic, and psychological cost that is not sustainable for too long. Shifting the focus onto the 'exit strategy' will be an urgent matter within a few months, if not weeks. From the way talk about exit strategy is currently framed, it might appear that it will be a matter of technical decisions or, as the Government put it, a matter 'of taking the right steps at the right time, informed by the best science'. But this is only partly true. Policy makers will need to show commitment to ethical principles and be able to justify decisions to sacrifice certain values and principles for the sake of others, which will be unavoidable. The exit strategy cannot be designed and implemented unless certain ethical decisions about trade-offs between different values are made. For example, decisions will need to be made about if and when to increase risk of illness or even death for certain individuals for the sake the psychological or financial interest of those who are being most heavily affected by the lockdown. Or to sacrifice to a certain degree privacy for the sake of public health in the use of contact-tracing technologies. Or again to use some level of coercion to enforce vaccination policies, when a vaccine becomes available. These decisions ar not merely about ""the best science"". These are ethical decisions. It will not be possible to make these decisions without having a plausible story about which values will at some point have to be prioritized, and why. This is not only because policy decisions need to be ethically acceptable (which is always a requirement, even in 'normal' times), but also because without appealing to certain ethical values, that go beyond merely technical considerations, it will be difficult to gain people's trust. This research will result in a set of recommendations, in the form of policy papers addressed to the relevant Government departments as well as academic papers, about how to make these necessary trade-offs between values in a way that can inform both public health policy and public health communication strategy. This project addresses, in chronological order, three core steps of the exit strategies that require close ethical scrutiny: 1) at what point, and through which steps, will it be acceptable to start the path back to some form of normality? 2) what kind of contact-tracing technologies (e.g mobile apps) can be used during the transition, and how? 3) when we have a vaccine, which vaccination policy should be adopted? There is also more general question about the level of coercion a Government may ethically enforce. This is an ethics project intended to inform policy making. As such, the methodological approach will be the standard one adopted in applied ethics projects, which include strategy to ensure the outcomes have practical relevance and provide feasible and easily implementable advice. I will test ethical intuitions against ethical theories and vice versa, in search for maximal coherence (""reflective equilibrium""), so that the conclusions will be as much as possible in line with shared values; use thought experiments - i.e. fictitious examples - to test future scenarios against hypothetical ones, in order to ensure the advice provided is consistent with people intuitions across various scenarios; survey different ethical points of view to identify strengths and weaknesses of each, to ensure ethical advice is informed by a pluralistic perspective.",2020,-99,University of Oxford,106196.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in the Allocation of Resources, +C01061,AH/V006835/1,Poets Respond to Covid-19: Collaborative UK and International Poetry Project,"Our project proposes the writing, exchange, publication and discussion of poetry as a significant cultural response, benefiting the UK (and global) public's processing, healing, and wellbeing during the COVID-19 pandemic. Our approach includes editing an anthology of 30 poets (15 UK / 15 other countries) responding to COVID-19, and an accompanying interactive website enabling collective public participation/engagement with poetry. CI and PI will situate poetry as a mode of response to COVID-19 in a multi-format essay speaking to our contemporary moment and within the context of other historical poetries of crisis (published in a peer-review journal, and also the anthology/website). The website (edited by PI/CI) will mitigate distancing and isolating effects of lockdown, inviting people to engage in forum discussions of COVID-19-related poetic performances and Q&A sessions. It will also provide a curated platform for public-submitted poetry responding to COVID-19. Target audiences include those suffering bereavement, physical or mental health issues, and those in need of 'wellbeing' (in line with the long-published research regarding the therapeutic value of reading and/or 'reflexive' writing of poetry). The print book (published 01/2021) formulates an immediate, static artistic response to COVID-19. The website will be edited for 12 months from the contract's proposed start (06/2020), enabling dynamic ongoing responses, exploring the impact of the virus as it requires ever-changing modes of engagement. The website further proposes value in its legacy-archiving and its exemplary use of digital technologies, enabling discourse (in this case, poetry) to be freely accessible during this crisis and future lockdowns.",2020,2021,University of Plymouth,109176.01,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health | Innovation,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01062,AH/R00384X/1,Postwar Urban Reconstruction in China 1937 - 1958,"The coronavirus pandemic has left city streets silent and passenger usage on public transport has plummeted. In the UK, the time to devise innovative strategies for managing people's access to urban public space and transport systems is now. This is so resources can be allocated effectively and people prepared through public messaging before the lockdown eases. This project will provide information on policies for managing public use of transport systems and urban spaces from China and Taiwan, and analyse the public reaction to them. In China, it will focus on the cities of Wuhan, which experienced an early initially uncontrolled outbreak and a severe lockdown, and Shanghai, where the authorities had some time to prepare. In Taiwan, it will focus on Taipei. The value of the comparison is that there are similarities in urban organization between Taiwan and China, but that the Taiwanese response has involved transparent governance and community consultation. In China, while there has been community support for many policies, there has been no public involvement in their design, and enforcement is more stringent. This project will proceed in two stages following the employment of a PhD student at Leicester as an RA. The RA is a native Chinese speaker, who will work under the PI's direction. This linguistic ability is essential to quickly engage with the complex the social media spaces in China and Taiwan. Month 1 (May): RA and PI to identify policies put in place related to access to public transport and public space in case study cities. A short report will be prepared summarizing these policies and sent to UK policy contacts. Months 2 - 7 (June - December): RA and PI to look at public response to these measures. This will use social media analysis (Weibo and Weixin in China, Facebook and Twitter in Taiwan), and more traditional print media. An initial report mapping the key trends will be followed up with a further report towards the end of the project, although if UK stakeholders request more regular updates this is possible. This will allow the research to respond flexibly to the development of the pandemic and the policy and public response to it.",2020,-99,University of Leicester,246402.46,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2018 +C01063,AH/V006924/1,Assessing the viability of access and benefit-sharing models of equitable distribution of vaccines in international law,"A vaccine is key to the COVID-19 global response strategy. However, it is not yet clear how any COVID-19 vaccine will or ought to be distributed, despite significant issues of fairness, equity, and justice. Developing countries may not have access to a COVID-19 vaccine without a governance framework guiding international allocation. It is likely that such a framework for vaccine distribution for COVID-19 will be developed through the World Health Assembly (WHA), with calls from governments already for this to happen. To date, there is only one existing international legal framework for the distribution of vaccines and other medical countermeasures, developed in the context of access and benefit-sharing (ABS) laws under the UN's Convention on Biological Diversity and its supplementary Nagoya Protocol. ABS forms the conceptual basis for the WHO's Pandemic Influenza Preparedness (PIP) Framework, the only dedicated ABS framework for pandemic vaccines. As a result, the PIP Framework provides a potentially useful starting benchmark to analyse a potential COVID-19 vaccine distribution framework. This project will assess the suitability of the ABS mechanism for COVID-19 vaccine distribution. This project uses responsive doctrinal legal analysis to assess the extent to which ABS can provide a legally robust framework on which to model the ethical global distribution of a COVID-19 vaccine. The project will rapidly publish its findings to help inform the development of a COVID-19 vaccine distribution strategy through the WHA and will publish a comprehensive analysis of the suitability of ABS mechanisms for future pandemic response.",2020,2021,Keele University,151963.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,"Medicines, vaccines & other technologies",2020 +C01064,ES/V003720/1,COVID-19: Supporting family carers in making decisions for older relatives with dementia,"Background: If an older relative with dementia with suspected COVID-19 becomes unwell quickly, family carers and the person with dementia may have to make rapid decisions. Decisions may concern hospital admission or whether to receive care at home, social distancing, and which treatments the person may or may not wish to receive. This can include very difficult decisions such as whether the person wishes to be resuscitated or have other potentially traumatic treatments. These decisions will have an impact on the emotional wellbeing of both the family and person with dementia. Aim: We will produce an evidence-based decision tool to support family carers and people with dementia to make these difficult decisions during COVID-19. Methods: This project will consist of three phases: 1) We will identify key factors influencing the choice of place of death in older people, conducting a rapid review of the evidence; 2) We will review and analyse common challenges and decisions family carers of people with dementia are making in relation to COVID-19, from the Alzheimer's Society online community forum. We will also explore concerns of people living with dementia during COVID-19 reported on the forum and; 3) Together with people living with dementia, family carers and health care professionals, we will develop a decision tool for family carers and people with dementia to use when making difficult decisions. Dissemination and Impact: The tool will provide carers with a clear framework to help them to make decisions and ease feelings of guilt, burden, stress, strain and anxiety. We will work closely with Marie Curie Charity, Alzheimer's Society and British Geriatrics Society to disseminate the tool and our findings to the people who may benefit from using them.",2020,-99,University College London,87194.3,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01065,ES/V003844/1,Modelling the Impact of the Coronavirus Pandemic on the UK economy,"This proposed project seeks to use and develop NIESR's modelling capability to estimate the short term impact of the coronavirus pandemic on the UK economy, and to assess longer-term issues on how the economic recovery is affected by different policy measures. An aim of this project would be to use the experience of modelling the coronavirus pandemic to establish a dynamic sectoral model of the UK economy that can be used in the analysis of supply-side policy issues. The model will be disseminated through the National Institute's NiGEM software package, which is widely used by UK and international policy makers.",2020,-99,National Institute of Economic and Social Research,81362.37,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01066,ES/V003879/1,Welfare at a (Social) Distance: Accessing social security and employment support during the COVID-19 crisis and its aftermath,"The benefits system is crucial to supporting people during, and after, the COVID-19 crisis but is under extraordinary pressure from an unprecedented wave of new Universal Credit (UC) applications. The benefits system therefore faces two significant challenges: (1) Urgently, to provide timely income and support to claimants. The wave of new applications places stresses on DWP processes (e.g. ID verification), exacerbating pre-existing concerns over the five-week wait for payment and the shift to a digitalised benefits system. Navigating this 'virtual' system often depends on in-person help (from e.g. advice agencies) and the extent to which claimants can access support remotely is unknown. (2) Later, helping claimants quickly return-to-work, whilst maintaining security for those out-of-work. Not only do 'new' claimants differ from existing claimants, but they are entering an altered system, with higher payments and reductions in conditionality/employment support. However, there is little knowledge about these new claimants, the operation of the 'new' system or the 'exit strategy' that follows. There is no time to waste; initial payments to the cohort of new applications are due late-April and major changes in the operation of the benefits system are likely to occur shortly after social distancing ends/relaxes. As such, this 18 month project will provide large-scale evidence on how well we are meeting these challenges and where the system is struggling in order to help policy makers and practitioners to develop rapid solutions. To provide this vital evidence, we will use the following methods: (1) Surveying claimants We will conduct an online survey of 8,000 new and existing claimants. We will start this within three weeks of commencing the project and go back to these people twice over the during of the project. (2) Case studies of claimant support We will also speak to the people who provide support to claimants. Using case studies of Leeds, Newham, Salford and Thanet, we will conduct 8-12 interviews (48 in total) with people providing this support (e.g. local authority, voluntary organisations, Jobcentres). (3) Interviewing claimants We will also carry out in-depth interviews with 80 claimants. These individuals will be interviewed twice (160 interviews in total) starting our first interviews in May. Participants will be recruited from both our survey and case study areas to ensure we include a diverse range of experiences.",2020,-99,University of Salford,648629.01,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01067,ES/V003887/1,COVID-19: Burden and impact in care homes - a mixed methods study,"The COVID-19 pandemic poses a substantial risk to elderly and vulnerable care home residents and COVID-19 can spread rapidly in care homes. We have national, daily data on people with COVID-19 and deaths, but there is no similar data for care homes. This makes it difficult to know the scale of the problem, and plan how to keep care home residents safe. We also want to understand the impact of COVID-19 on care home staff and residents. Researchers from University College London (UCL) will measure the number of cases of COVID-19 in care homes, using data from Four Seasons Healthcare, a large care home chain. FSHC remove residents' names and addresses before sending the dataset to UCL, protecting resident's confidentiality. Since we cannot visit care homes during the pandemic, we will hold virtual (online) discussion meetings with care home stakeholders (staff, residents, relatives, General Practice teams) every 6-8 weeks, to learn rapid lessons about managing COVID-19 in care homes and identify pragmatic solutions. Our findings will be shared with FHSC, GPs and Public Health England, patients and the public, and support the national response to COVID-19. Patients and the public will be involved in all stages of the research.",2020,-99,University College London,211293.08,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01068,ES/V003941/1,English Longitudinal Study of Ageing COVID-19 Substudy,"The COVID-19 crisis is having an unprecedented impact on people's lives from the perspectives of their health, psychological wellbeing, social activity, employment and financial circumstances. Older people are at high risk because of the presence of long-term health conditions, problems with mobility, as well as social isolation due to lower levels of internet use compared with the rest of the population. The repercussions of this crisis will be considerable and long-lasting. Research for years to come will need to understand who has been most affected economically and socially, and how policymakers can best help them in the long run. Additionally, researchers need to study the crisis now, and policymakers' responses to it, in order to make future health and social systems more resilient to such events in the future. There is a strong scientific case for collecting data in the time of the crisis within the framework of existing longitudinal data and infrastructure investments that already form a large part of the evidence base when it comes to understanding the links between health, economic welfare, family and social structures. There is an urgent need to monitor these processes in order to identify the extent of adverse experience, to learn how to promote resilience, and to inform policy. ELSA is uniquely positioned to do this for older people. Our aim is to carry out assessments of a large well characterized sample of men and women aged over 50 who are participants in the long running English Longitudinal Study of Ageing (ELSA). We will implement an internet assessment of the complete sample (more than 9,000 people), with telephone interviews to ensure people who are not able to use the internet can participate. We will measure experiences of COVID-19, changes in financial circumstances, work and caregiving, mental and physical health, social contact and loneliness, health and social care, stress and worries. The survey will be carried out in June 2020, with a second assessment in September/October. The study will inform policy makers and researchers about the diverse impacts of COVID-19.",2020,-99,University College London,525683.61,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts, +C01069,ES/V003968/1,The impact of the COVID-19 crisis on nutrition,"A major challenge facing policymaking during the COVID-19 crisis is ensuring all households have access to a nutritious diet. The Department of Environment, Food & Rural Affairs (DEFRA) have provided supermarkets with a list of 1.5 million vulnerable people in England; this is being used to determine eligibility for grocery deliveries. However, there are press stories that families are struggling to put adequate food on the table. And in the devolved nations there are delays in supermarkets obtaining information on who the vulnerable are. Many households are under significant financial pressure, some low-income families have lost access to free school meals, and interrupted supply chains and hoarding by some consumers are leading to significant upward pressure on food prices. We will provide evidence on whether vulnerable people - e.g. the elderly, those on low incomes, and those with young children - are having difficulties accessing essentials and maintaining a healthy diet. We will use real-time longitudinal data on a large representative sample (over 30,000 households) to provide a systematic analysis of how different people's food spending is changing over the crisis relative to pre-crisis spending patterns. We will show how prices have changed and how the crisis is impacting the number of calories different people buy, how they obtain these calories (e.g. food out, takeaways or home cooked), the balance across different types of foods, and the overall quality of people's diets. Our analysis will provide timely, invaluable information to policymakers tasked with ensuring a food supply chain that functions for all.",2020,-99,Institute for Fiscal Studies,136427.68,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts, +C01070,ES/V003798/1,Child Protection and social distancing: Improving the capacity of social workers to keep children safe during the COVID-19 pandemic,"This research will explore the impact of the COVID-19 pandemic on child protection, social workers and service users, with specific reference to the novel use of digital technologies in a period of institutionalised social distancing.",2020,-99,University of Birmingham,361976.04,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Social Workers,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2020 +C01071,ES/V004042/1,The Impact of COVID-19 on Economic Inequality and Employment Progression,"The applicants have already collected novel survey data from a large representative sample of UK workers on 25th March 2020. We find large and significant differences in the impact of the economic disruption across workers of different income levels, ages, and those employed under different work arrangements. They seek funding for five follow-up waves of representative survey data to enable the impacts of the crisis on different workers to be tracked and to assess the effectiveness of different policies aimed to smooth the effect of containment measures on living standards. Using a specialised survey company, we will survey a representative sample of UK workers in mid-April, mid-May, mid-June, and two longer term follow-ups depending on the duration of containment measures.",2020,-99,University of Oxford,84269.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01072,ESRCCOVID007,COVID-19: Harnessing Existing Research to provide Rapid Responses,"Our audit of NIESR research has identified four specific strands that could have immediate impact on policy formation or understanding of the coronavirus crisis. These are the use of our world-leading econometric model to provide new analysis for HMG and other bodies; the roll out of two existing products which will enhance the economic impact of the virus in real time; application of recent work on the public understanding of economic and policy messages to the communication of government policy and application of our understanding of specific disadvantages groups to provide new analysis of the impact of the virus in less advantaged, deprived and migrant communities.",2020,-99,National Institute of Economic and Social Research,103414.01,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Communication | Policy research and interventions | Social impacts",2020 +C01073,ESRCCOVID009,Coronavirus Economics Translational Hub,"The aim of the hub is to provide possible options and answers to questions that policy makers, the public and students have about the economics of the crisis caused by coronavirus and issues raised by post-crisis recovery, drawing on a wide range of research.",2020,-99,Institute for Fiscal Studies,331575.89,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01074,ES/V010069/1,"Remote-by-Default Care in the COVID-19 Pandemic: addressing the micro-,meso-, and macro-level challenges of a radical new service model","AIM In the context of COVID-19, to address micro- (technical tools, clinical techniques), meso- (organisational change) and macro (national infrastructure) aspects of a remote-by-default service model in primary care. OBJECTIVES 1. Validate and embed evidence-based tools for remote assessment and monitoring. 2. Support local implementation teams to overcome technical, operational and professional barriers and implement remote-by-default service models rapidly and at scale. 3. Generate and apply insights on how NHS infrastructure can better support and be supported by digital innovation in a time of crisis. RESEARCH QUESTIONS 1. How can technology support assessment and monitoring of patients at a distance? 2. How can we achieve rapid spread and scale up of remote-by-default models of primary care? 3. What insights can we glean from this time of crisis that will help build a more resilient NHS? OUTLINE METHODS 1. TOOLS: Qualitative research to develop instruments followed by quantitative validation studies. 2. IMPLEMENTATION AND SCALE-UP: Four contrasting case studies in different localities, nested in an over-arching analysis of national policy. Action research (informed by interviews, ethnography, documents, datasets) by virtual researchers-in-residence. 3. WORKSHOPS AND SCENARIO-TESTING: Involving policymakers, regulators, professional bodies, industry, patients/citizens, to identify ways to strengthen infrastructure for rapid change.",2020,2021,University of Oxford,462164.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,"Health service delivery | Medicines, vaccines & other technologies",2020 +C01075,ES/V004050/1,COVID-19: Identifying effective remote literacy teaching methods for primary-aged children,"This research project stems from a direct appeal from our UK teachercollaborators, who suddenly face having to teach pupils online, with scant training and patchy evidence on how to do so effectively. We aim to identify effective remote, evidence-based literacy instruction for primary-aged children with a range of literacy abilities; to mitigate as much as possible the negative effect of school closure on education. Implementing a longitudinal design, we will assess literacy outcomes before,during, and after two five-week cycles of online teaching. We focus on literacy instruction, given that literacy is core to primary education, and a crucial predictor of later educational achievement. We focus on the understudied topic of effective online delivery. 120 Key Stage 2 children will undergo remote one-to-one teaching, in which each child receives one cycle of (a) live interaction, simulating a classroom environment (synchronous),and one cycle of (b) independent work on tasks à live feedback/discussion fromthe teacher, often used in online class (asynchronous) methods, delievered in a counterbalanced curriculum over the two cycles. 120 age- and ability-matched children currently not undergoing structured formal teaching will form a baseline.Literacy outcomes will be assessed remotely, using standardised tests. Testing takes place before and after the first cycle (T1: May; T2 June), after the second cycle (T3: July), and nine weeks later (T4: November), to examine sustained benefits derived from instruction, and the longer term impacts of school closures on literacy, through modelling with the previous year's cohort data.",2020,-99,Bangor University,143995.81,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01076,ES/V00414X/1,A duty of care and a duty to teach: educational priorities in response to the Covid-19 lockdown,"This research explores the challenges the Covid-19 crisis sets primary schools, using surveys and telephone interviews to analyse how teachers weigh a duty of care (for their pupils' well-being and welfare) and a duty to teach (given their responsibilities for curriculum delivery) in their interactions with families during the lockdown. By tracking teachers' immediate responses and longer term reflections, the research will explore the extent to which the crisis is challenging and reshaping shared understandings of the purposes and values of primary education. This will be considered in the light of the diverse roles primary schools find themselves playing as supportive community hubs during the crisis. By conducting the research within a short time frame, and comparing teachers' actions and perceptions with the concerns expressed in public debate on the impacts of Covid-19 on education, alongside the most relevant research studies, the findings will be able to i) inform decisions that will need to be made about how schools resume ""business as usual"" post lockdown, including any implications for high stakes tests and inspection and ii) set an agenda for public reflection on the social role schools should play in their communities through the ways in which they combine a duty of care with a duty to teach.",2020,-99,University College London,94175.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01077,ES/V004433/1,COVID-19: Food and Nutrition Security during and after the COVID-19 Pandemic,"The COVID-19 pandemic is having substantial consequences on UK and global food and nutrition security (FNS). This project will undertake world-leading research to provide government, business and decision makers with the evidence that they need to develop a robust FNS response to the current pandemic. The pandemic is causing major shocks to the four pillars of FNS: access; availability; utilisation and stability. Examples include reductions in productivity (labour limitations), breakdown of norms of food systems (distribution, changed demand) and supply chain restrictions (agri-chemicals for crop management). Economic impacts are altering both supply, distribution and demand. Collectively these shocks are substantially altering food systems whilst in the longer-term norms of trade may not adapt appropriately leading to changes in the balance of traded commodities, reduction in food reserves and price increases. The project focusses on UK FNS which is heavily dependent on global markets. Half of the food we consume is imported and UK livestock industries rely heavily on imported feed. Some countries have already restricted exports in order to supply home markets. Normal market forces, transportation and distribution networks may no longer be appropriate to provide national requirements. A priority is to understand how to increase capacity for self-reliance to maintain civic stability, a healthy population and to understand the ramifications for third countries. The aim of this study is to conduct an initial rapid FNS risk assessment and explore options for changes in agricultural production, trade and distribution to protect FNS without jeopardising wider ecological and climate goals.",2020,-99,James Hutton Institute,419425.41,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01078,ES/V004263/1,Impact of COVID-19 on Staff Mental Health and Well-Being in SMEs:Strategies and Interventions to Support Workforce and Boost Productivity in the UK,"COVID-19 pandemic has led governments globally to respond with unprecedented lockdown and economic measures to combat spread of the disease, and support workers and businesses. The pandemic presents a real threat to small and medium sized enterprises' (SMEs') workforce mental health (MH) and well-being, and employers need to pursue serious plans to support their workforce (16m) in the UK. There is limited evidence in this regard and research is needed from a multi-disciplinary perspective on best strategies, interventions and policies informing SMEs (99.9% of UK businesses) regarding how to support the staff and enhance their productivity. The main objectives of this project are to: (1) Develop a conceptual model that will facilitate analysing the relationship between MH issues faced by SMEs' staff, factors and various job dimensions contributing to these issues, and its impact on both the staff and business productivity during the pandemic, through a multi-stage survey with 1200 SMEs' employees in the UK; (2) Develop a COVID-19 employee well-being framework comprising of strategies, practices and interventions, considering SMEs' needs and constraints, and conduct a longitudinal study for six months with twenty SMEs to evaluate its effectiveness and impact towards increasing the resilience and productivity of SMEs' workforce in varying work contexts during and after the pandemic; (3) Develop a COVID-19 MH application to monitor the MH conditions of SMEs' workforce and pilot it with the longitudinal study, to show how the data collected through the app will enable each individual SME to understand its staff needs, introspect their well-being, that will facilitate customizing the framework, i.e. objectively putting in place practices, strategies and interventions to address employee MH, well-being and firm's productivity related issues.",2020,-99,Aston University,247993.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01079,ES/V004581/1,COVID-19: Safety and personalisation for UK maternity care provision during and after a pandemic.,"Annually, over 1,200,000 UK residents (pregnant women and neonates) need maternity care. All relevant authorities emphasise the critical importance of antenatal, intrapartum, postnatal and neonatal services, birth companionship, keeping mother/baby together, and breastfeeding, even during COVID-19. International disaster reports consistently value community provision. These principles align with NHS England Better Births safety and personalisation policies. UK maternity Trusts have responded differently to COVID-19. Some have reduced tests, contacts, community intrapartum provision, and birth companionship options. These decisions are associated with reports of unattended home births, delays in self-referral for unusual symptoms, and psychological distress. In other Trusts, and in countries such as The Netherlands, increased community care provision, and new innovations (including remote access to tests and contacts) are being trialled. With stakeholders, and using normalisation and behavioural change theories, we will identify which organisational responses have worked best for maternity care organisation during COVID-19. We will undertake policy level UK/Netherlands analyses, using official documents, national level interviews, and a geo-mapped on-line survey of women's experiences before, during and after COVID-19. We will then undertake in-depth maternity/neonatal case studies in 8 UK Trusts, selected on available staffing levels at the crisis peak, and on case-mix. We will include retrospective and prospective documentary reviews, on-line staff and parent interviews, routine clinical outcomes data (including infections), and modelling of what worked to optimise safety and personalisation for women, parents, and staff. A final stakeholder event will co-develop a practical, theoretically informed organisational model for both routine and crisis-affected maternity and neonatal services.",2020,-99,University of Central Lancashire,607254.57,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom | Netherlands,Health Systems Research,Health service delivery, +C01080,ES/V004107/1,"COVID-19: The local as a site of food security resilience in the times of pandemic: opportunities, challenges and ways forward.","The COVID-19 pandemic has significantly impacted on the UK's food systems, and disruptions are likely to continue. There is emerging evidence that the local food sector (local food producers and their supply chains) can significantly contribute to the resilience of the UK's food system at this time. However, robust data is needed to better understand the impact this sector can make on food security during and after the pandemic, and to help maximise its contribution. By working closely with key businesses and organisations in the local food sector, this 5-stage project will use surveys, interviews, citizen science, and backcasting to provide timely evidence on1. the sectors' robustness, capturing the impact of and response to the pandemic (deliverable 1);2. its adaptability, gathering information on adaptation by local producers, short chains andintermediate actors (deliverables 2 & 3);3. its route to transformation in the post-pandemic context, assessing longer-term changes atsupply chain and policy levels (deliverables 4 & 5).The project will collect and feeding back robust data, and by providing structured space for sectorwide collaboration and long-term planning. It will thu enable the business and policy actors on local and national levels to maximise the local food system's contribution to UK's food security, and to ensure its sustainability and resilience. This project has significant buy-in from key businesses and organisations in this sector, as well as policymakers, as evidenced by letters of support. It is therefore highly likely to ensure high participation rates and deliver significant impact.",2020,-99,The University of Sheffield,194931.04,Human Populations | Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01081,ES/V004255/1,Necessary discussions: Advance care planning for nursing homes in a COVID-19 outbreak,"It is likely that nursing homes in the UK will become clusters in their communities for the worst clinical manifestations of COVID-19 (1). Since all nursing home residents are at substantial risk, nursing home care staff need to know what residents would want to happen should they become infected with COVID-19. The aim of this project is to develop and evaluate an online advance care planning (ACP) COVID-centric intervention for nursing homes during a COVID-19 outbreak to improve care at the end of life. Findings from a rapid review of available resources will be used to develop an online ACP COVID-centric intervention for training nursing home staff and providing an information resource to family carers. To evaluate the intervention, we will conduct a prospective case study design where a nursing home will be the unit of analysis or 'case'. Nine nursing homes will participate in the project with three nursing homes located in Northern Ireland, England, and Scotland. We will collect data from up to 54 family carers and 45 nursing home staff. Expected outcomes: (a) enhanced knowledge of conducting end of life discussions during COVID distancing measures; (b) improved ability for staff to assess resident needs and respond more appropriately in relation to ACP; (c) enhanced decision making among family members regarding resident care; (d) improved communication between staff and family carers regarding their relatives health care needs; (e) increased evidence of completed ACPs; (f) development of open source online ACP COVID-centric resources for use by nursing homes.",2020,-99,Queen's University Belfast,161779.95,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01082,ES/V004077/1,The impact of Covid-19 restrictions on recreation and use of green space in Wales,"The use of green spaces for recreation has acknowledged benefits for physical and mental health, to the extent of reducing mortality rates [1]. Green spaces include parks and gardens in urban areas, and the wider countryside in more rural settings. There is, however, great inequality in access to green spaces for different sections of society. People from more deprived backgrounds suffer from a lack of quality local green space, but also the means to travel to more distant green space, and use of green spaces tends to decrease with age. A key policy aim is to increase use of green spaces by all sectors of society.Variation in people's use of green spaces remains poorly understand. The social distancing regulations implemented during the Covid-19 pandemic both restrict travel, but also emphasise the importance of exercising locally. This provides a fascinating 'natural experiment' into how the use of green spaces is affected by these regulations. In particular, do we find that different sections of society are affected differently as distant travel is discouraged, but permitted exercise increases use of local green spaces?In January 2020, we surveyed >1000 people, obtaining a representative sample from across Wales. Data showed where, why and how people access green spaces, and the benefits they derive. Repeating this survey during the period of restricted travel and as the UK recovers from the coronavirus crisis will provide unique insight on how people benefit from natural spaces and how this was impacted by Covid-19.1. http://researchbriefings.files.parliament.uk/documents/POST-PN-0538/POST-PN-0538.pdf",2020,-99,Bangor University,13321.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01083,ES/V004379/1,A longitudinal mixed-methods population study of the UK during the COVID-19 pandemic: Psychological and social adjustment to global threat,"The impact of the COVID19 pandemic on public mental health will affect need for services, further progress or resolution of the pandemic and speed of economic recovery afterwards. Policymakers have emphasised the need for a whole population approach to studying mental health during pandemics but no such study has yet been conducted. With initial funding from the Universities of Sheffield and Ulster, early in the crisis we began collecting longitudinal data from a sample of 2,025 UK adults that is representative of the population in age, sex, household income, etc., measuring anxiety, depression, health behaviours, political beliefs and other relevant variables using standardised measures. We have reported our detailed methods, (https://psyarxiv.com/wxe2n) mental health findings (https://psyarxiv.com/hb6nq) and health psychology findings (https://psyarxiv.com/typqv) from wave 1. Wave 2 follow-ups began on 21th April. Having established the earliest, most comprehensive study of mental health and social adjustment in any pandemic we now seek funding for 6 more waves of survey data from the same respondents (with resampling to replace panel attrition) beginning Wave 3 between May 18th and March 2021. The survey is supplemented by detailed studies of subgroups using qualitative interviewing, cognitive methods and momentary assessment. This and successive waves will allow us to report timely data on changes in mental health and psychosocial functioning from beginning to end of a pandemic for the first time, identifying vulnerable groups needing help. Our findings are being used by the Cabinet Office, Public Health England and Scotland and the Department of Health and Social Care.",2020,-99,University of Sheffield,480289.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01084,ES/V004867/1,Real-time evaluation of the effects of Covid-19 and policy responses on consumer and small business finances,"The project involves the creation of a new real-time economic characterisation of consumer and firm behaviour from mass transaction data. Specifically, the work will evaluate impact on consumer finances (reduced incomes, non-payment of debts, patterns of saving and expenditure) and small business finances (turnover and business continuity). The research will be co-produced with four organisations.",2020,-99,University of Warwick,291693.48,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01085,ES/V00445X/1,Reducing the Unanticipated Crime Harms of COVID-19 Policies,"The COVID-19 crisis is changing the shape of crime. Drawing on crime science, this research will inform evidence-based policy and practice. we will anticipate crime effects of prolonged, graduated or cyclical exit strategies. We will use (1) national police data, (2) detailed data from three police partners, (3) fraud and ecrime data from industry, and (4) sources from other agencies such as Childline (for unreported crime).",2020,-99,University of Leeds,653991,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",, +C01086,ES/V004921/1,COVID-19 and Child Criminal Exploitation: Closing Urgent Knowledge and Data Gaps on the Implications of Pandemic for County Lines,"Our research will assess changes and continuities in perpetrator behaviour resulting from social distancing, showing whether criminal business models are likely to change due to a changing risk and/or profitability profile. This project will detail the impact of social distancing measures on offenders' ability to groom, methods for mobilising 'county lines' operations, and the prevention, detection and safeguarding abilities of police and other organisations. It will use a single case-study design.",2020,-99,University of Nottingham,217194.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01087,ES/V004891/1,"COVID-19: Families, children aged 0-4 and pregnant women: vulnerabilities, resources and recovery in Tower Hamlets","Adverse impacts of the current COVID-19 pandemic will disproportionately fall on individuals and families at the lower end of the income distribution. The highly diverse population profile offers an opportunity to identify how families deploy their interpersonal, economic and social resources to manage risks associated with living in lockdown restrictions and its aftermath. In close partnership with the borough Public Health team, we will run a repeat survey of 2000 couple and single parent families with children aged 0-4, and pregnant women; a longitudinal qualitative panel with approximately 60 household members including fathers and wider kin; and examine changing family support services, and emergent community resources such as mutual aid and peer networks",2020,-99,University College London,370742.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01088,ES/V004859/1,Assessing financial vulnerability and risk in the UK's charities during and beyond the COVID-19 crisis,"This research will provide an analysis of the variegated impacts on charities of the very severe financial constraints they will experience due to the immediate and longer-term economic effects of the COVID-19 crisis. Building on our extensive prior research on the finances, distribution and exposure to risk of charities we will utilise large-scale databases constructed since 2008 to assess the distribution of financial vulnerability across the population of charities.",2020,-99,University of Birmingham,293120.48,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01089,ES/V004913/1,The geography of post COVID-19 shutdown recovery risk in UK economic activity. Implications for recovery inequality and targeted stimulus,"The COVID-19 shutdown is not affecting all parts of the UK equally. Economic activity in local consumer service industries (LCSI), such as retail outlets, restaurants, hairdressers, or gardeners has all but stopped; other industries are less affected. This project will produce data measuring the shock, the multiplier, and the COVID-19 shutdown recovery risk for UK neighbourhoods. These variables will be estimated using a wealth of individual and firm level information from national survey and administrative data.",2020,-99,University of Sheffield,118150.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01090,ES/V004905/1,COVID-19 App Store and Data Flow Ecologies,"Mobile phone applications (apps) have emerged as a key part of the response to COVID-19 around the world and are a feature of UK government plans to manage 'phase two'. While raising concerns from privacy and security to the adoption rates required for their effectiveness, initial research on COVID-19 apps has either remained abstract, been conducted in an ad hoc manner or has targeted individual apps.This project will deliver a systematic empirical analysis of: 1) emerging ecologies of COVID-19 apps and their governance through app stores, and; 2) the data flows of prevalent apps within this domain. Through these combined methods, the project will provide an assessment of the governance risks and challenges posed to the public by COVID-19 apps.",2020,-99,University of Warwick,59237.11,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Other secondary impacts, +C01091,ES/V004840/1,Covid-19: What are the Drivers of the Islamophobic Infodemic Communications on social media,"The research project will examine the interaction between miscommunications and conspiracy theories in relation to key factors such as anonymity, membership length and peer groups, within the context of the current Covid-19 pandemic on social media. The research will explore irrational beliefs and thoughts that are disseminated on social media, covering important coverage of communications surrounding conspiracy theories online whilst paying particular attention to content associated to racist infodemic messages.",2020,-99,Birmingham City University,175247.5,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C01092,ES/V004956/1,"Entrepreneurial resiliency, innovation, and change during the COVID-19 Crisis","Entrepreneurship is a critical part of the Government's economic development efforts and is a major goal for local and devolved governments. However, the COVID-19 crisis threatens many entrepreneurial firms. Existing research on crisis management and resiliency is oriented towards large multinational firms and gives little guidance to how entrepreneurs can protect their companies and innovate their business models in times of uncertainty. This project will investigate how entrepreneurs across the country are reacting to this crisis. Through interviews with 60+ high-growth commercial and high-impact social entrepreneurs we will identify the immediate strategies entrepreneurs use to limit the damage done to their firms. Repeated interviews over the next 18 months will show how these strategies evolve from damage control to planning how to redeploy their existing resources and create new capabilities to take advantage of new market niches created by the COVID-19 pandemic. These interviews will produce a detailed and nuanced perspective on how entrepreneurs react to crisis and how these reactions change over time. Findings will be rapidly communicated to the entrepreneurial community to share best practices and local and national policymakers to help them craft the most effective policies for aiding the recovery of country's entrepreneurial economy.",2020,2021,University of Edinburgh,290603.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01093,ES/V004387/1,COVID-19: Measuring the effects of Covid-19 on businesses and the UK economy,"This application addresses two of the key objectives of this grant scheme by • gathering critical data on the business response to Covid-19 quickly for immediate policy and future research use. • providing new research with a clear impact pathway that has the potential to deliver a significant contribution to the understanding of, and response to, the Covid-19 pandemic and its impacts on UK businesses. We draw on our experience from the Decision Maker Panel (ESRC-BoE-funded), Business Impact of Covid Survey (ONS-funded) and Management and Expectations Survey (ESRC-ONS-funded) coordinated through the Economic Statistics Centre of Excellence (ESCoE). We will • Collect information fortnightly/monthly on Covid-19. Responses from businesses are immediately used for policy decisions in real time by Bank policy committees (MPC and FPC), HM Treasury, BEIS, 10 Downing St and COBRA. • Formulate and cognitively test Covid-19 questions. A Business Engagement Group including McKinsey, CBI, CMI, Be the Business, BEIS will assist us. • Create a data archive offering a matched dataset using administrative data and ONS surveys to provide detailed analysis of the immediate impact on employment, investment and sales growth using state of the art dynamic panel methods in Stata. • Assess the resilience to shocks from a survey focused on management practices updated with Covid-19 questions prior to placement in the field in September 2020, to document the ability of better- (worse-) managed firm to respond to shocks. • Evaluate the impact on businesses over the next 18 months regarding business performance (productivity), use of debt, digital technology, working practices, supply chains etc.",2020,-99,University of Nottingham,804012.61,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01094,ES/V004549/1,Transitions to more harmful forms of gambling during Covid-19 pandemic: behaviours and targeted marketing in young people and bettors on sport,"Around 2 million people experience harms from gambling, and many gamble on live events (including sports) and online. The COVID-19 pandemic has precipitated unprecedented restrictions on people's movements and interactions in public and private settings, and led to the cancellation of major sports events and social activities. These consequences of the COVID-19 'lockdown' have altered the gambling landscape worldwide. There is an urgent need to provide regulators, policy makers and treatment providers (e.g. World Health Organisation (WHO), Gambling Commission, All Party Parliamentary Group on online gambling harms) with high quality evidence on the changing patterns and context of gambling behaviours during COVID-19 and its aftermath. Insight is needed into: the actions undertaken by industry so regulators can consider immediate actions; understanding of new risk groups susceptible to gambling harms to develop effective prevention strategies; and understanding of the escalation and maintenance of harms to inform treatment and support provision. To meet this need, we will address three major research questions across three integrated workpackages: 'How has COVID-19 changed gambling practices, and the risk factors for and experience of gambling harms?'; 'What is the effect of COVID-19 on gambling marketing?'; and 'How has COVID-19 changed high risk groups' gambling experiences and practices?'. Drawing on our extensive experience of mixed-methods research, we will focus on two groups at particular risk of adopting more risky, online gambling practices - young adults and sports bettors. The team will draw on their strong network of stakeholder partnerships to ensure timely dissemination and impact.",2020,-99,University of Stirling,712255.1,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01095,ES/V00476X/1,Domestic Abuse: Responding to the Shadow Pandemic,"Domestic violence is a severe problem in the UK, but the social isolation regulations imposed in March 2020 have exacerbated dangers (""a perfect storm for controlling, violent behaviour behind closed doors""). Media coverage has intimated the likely impact of the 'stay at home' directive on the nature and extent of domestic abuse. Evidence suggests that this has already taken its toll on the rates of intimate partner homicide, and that the number of assaults and murders will continue to rise considerably this year. In April, the 2020 Home Affairs Committee noted that the police are currently struggling to protect the vulnerable. Several forces have innovated, introduced digital reporting, and new types of emergency responses in order to protect victims. The courts are also struggling to hold trials and sentence domestic violence offenders, and the backlog in cases is likely to mean that victims will be dissuaded from taking cases to court. This project will evaluate the efficacy of policy and practice innovations by both the police and courts to deal with the immediate crisis and explore their viability for future practice in face of ongoing service demands and the fiscal impact of such as the longer-term consequences of the global pandemic take root. The research team, which consists of experienced experts in the field, will work together with CJS partners to produce fast-delivery reports in order to facilitate shared good practice in the social-isolation period and its immediate aftermath; and explore longer-term trends which emerge in the next eighteen months.",2020,-99,University of Liverpool,394603.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01096,ES/V006320/1,"Identity, Inequality, and the Media in Brexit-COVID-19-Britain","COVID-19 and Brexit are extraordinary social and political processes that are occurring simultaneously. These events are exposing the major inequalities that underpin British society across class, ethnic, national, migrant, generational and geographical identities. They are also both high profile public events and processes that generate media and government information. The proposed research sets out to examine the resonances and contrasts in the ways in which the inequalities of COVID-19 and Brexit have been framed by the media and everyday experiences. Understanding these inequalities and their potential effects on social and political polarisation is crucial to answering how and in what shape British democracy emerges from Brexit and COVID -19. To do this, we will conduct new research on individual experiences and media narratives that builds on existing data collection about Brexit Britain. By building on this previous research, we can provide a unique longitudinal understanding of the social and political impact of COVID19 in Brexit Britain. The research will begin in May 2020 with the first wave of a panel survey and initial media content analysis collected during the lockdown period, with a second wave of the panel survey taking place in September 2020 when it is expected that some restrictions will have been lifted, and a third wave in January 2021, which will provide the context for and coincide with the beginning of six months of ethnographic research with participants we previously interviewed as part of a Brexit project.",2020,-99,University of Exeter,443578.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C01097,ES/V007033/1,Responding to the Covid-19 domestic abuse crisis: developing a rapid police evidence base,"The proposed project provides a near real-time evidence base to inform the police approach to the apparent surge in domestic violence and abuse (DA) triggered by the Covid-19 lockdown in the UK. Police case file data from seven diverse police forces are pooled to track the impact of the pandemic on DA, analysing changes in the risk factors, frequency, nature and profile of DA reported to police. These changes are mapped closely to shifts in the restrictions imposed during lockdown, transitional phases and post lockdown, when DA calls to police are expected to spike. The proposed study is the largest and most rigorous analysis of police DA case file data conducted anywhere in the world to date. The statistical analysis is complemented by regular focused semi-structured phone interviews with police officers, to identify emerging challenges and best practice in the frontline response to DA. The mixed-methods study addresses urgent questions on the impact of Covid-19 on DA, which may have significant implications for the complex task of accurate police risk assessment, victim safeguarding, and criminal prosecution as the Covid-19 pandemic evolves. The Home Office, the National Police Chiefs Council (NPCC), and College of Policing (CoP) are project partners and constitute direct links to critical decision-makers and provide direct routes to impact. A timely and evidence-based development of a police strategy is urgently needed to address the emerging DA crisis and its devastating, longlasting consequences for victims and their children.",2020,-99,City University of London,173913.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01098,ES/V007270/1,The Real-Time Economic Effects of Covid-19 in the United Kingdom,"This project will examine the microeconomic impacts of the Covid pandemic and lockdown on UK businesses and its interaction with the UK's decision to leave the European Union. The project will deliver two key outputs, which are fundamental to designing and monitoring appropriate policies to mitigate the negative economic impacts of Covid. A first key output will be to provide real-time monthly summaries of the impacts of Covid on UK businesses and their expectations of business and employment outcomes for the coming months. This will use confidential information from firm-level surveys conducted by the Confederation of Business Industry (CBI), made available to us through a special agreement between CBI and the Centre for Economic Performance. The data are unique in providing rich, real-time, firm-level information on current trends and expectations. The surveyed firms have a broad coverage of sectors and regions and our previous work shows that they can deliver nationally representative economic analysis. Supplementing CBI survey data with firm and industry characteristics from ONS and company accounts, a second key output of the project will examine the channels through which businesses are being affected by Covid, such as demand, supply chains, and finance, and the interaction (if any) between these impacts and the effects of Brexit. The project will identify the heterogeneity of impacts by firm-size, sector, and region, and the evolution of business activity as the economy recovers and the UK leaves the EU. The granular findings will help design detailed policy responses.",2020,-99,London School of Economics and Political Science,195032.88,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01099,ES/V005529/1,"DETERMIND-C19: Impact of COVID-19 on people newly diagnosed with dementia and their family carers, a mixed method study nested in DETERMIND","People with dementia are at high risk of adverse outcomes from COVID-19 and may also be adversely affected by the steps taken by society to control the spread of the infection. They have difficulty remembering and understanding restrictions and precautions put in place to protect them and others, and may be distressed that non-resident family and social networks are compromised. In addition, there is currently reduced access to many formal care services. This may cause strain for people with dementia and co-resident and non-co-resident family carers, particularly those with a recent diagnosis who are attempting to come to terms with living with dementia and navigating the complex support landscape. We currently have few empirical data with which to help us to formulate how best to support them. We will address this gap by examining how a group of 266 people newly diagnosed with a range of severities of dementia in the months before the COVID-19 lockdown and their carers have been affected by COVID-19 and the predictors of better and worse outcomes (quality of life, depression, carer burden and physical health). They were recruited as part of the ESRC/NIHR-funded DETERMIND programme and have a rich baseline characterisation of socio-demographics, clinical state, and service use. Using telephone quantitative and qualitative interviews we will investigate what has happened to them and how outcomes vary by clinical and sociodemographic factors such as dementia severity, neuropsychiatric symptoms, service receipt, ethnicity, gender, and place of residence. We will use these data to generate practical guidance for services and families on how best to support people with dementia and carers in this and any future pandemic.",2020,-99,University of Plymouth,115124.5,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical | Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01100,ES/V005200/1,Waste management during the COVID-19 outbreak: Investigating a critical sector in crisis,"The COVID-19 outbreak is transforming everyday household waste into a biohazard. Coronaviruses are transmitted person-to-person, however COVID-19 also persists on surfaces for several days (van Doremalen et al. 2020). Consequently, this pandemic is severely impacting the waste management sector; causing disposal and recycling service disruptions, and putting waste workers at risk. Before the emergence of COVID-19 this heavily marketised and deregulated sector - comprising over 3,000 companies - was already associated with elevated rates of death and injury compared to other sectors in the UK (HSE 2019). This project asks to what extent the UK waste management sector is equipped to meet the unprecedented challenges generated by this pandemic. The interdisciplinary project works in partnership with national industry associations and local authorities to investigate how this critical sector is responding to, and affected by, COVID-19 - particularly in terms of the safety of its workers. It aims to mitigate hazards related to waste management during the outbreak through three interrelated approaches: 1) the project generates urgent data on the sector's rapidly changing waste management practices. It employs social research methods to examine pivotal processes, including collections, disposal, and administration; 2) the project collaborates with key workers to map the sector and design a pandemic toolkit that can amplify workers' voices in decision-making; and 3) in collaboration with the Waste Industry Safety and Health Forum, this project creates guidelines and an industry report to enable greater co-ordination between authorities. This research addresses both the immediate crisis and contributes to future preparedness plans.",2020,-99,University of Exeter,303770.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C01101,ES/V005383/1,Facilitating the public response to COVID-19 by harnessing group processes,"There is international recognition that effective response to Covid-19 is dependent upon the public acting collectively and for the common good. This is important in terms of adherence to preventative measures, which, especially for low-risk groups, is as much about protecting others as protecting oneself. It is important in terms of volunteering and mutual aid, which is critical in complementing the official response by supporting and sustaining people through the pandemic. It is also important in terms of maintaining social cohesion and avoiding social disorder. This multi-method project builds upon understandings of psychological group processes to address how to develop and sustain shared identity and social solidarity during pandemics. It is organised around three interrelated strands that together address the issues of adherence, mutual aid and social order. The first strand uses experiments to examine the impact of collective identification on adherence, the role of leadership in developing collective identification, and how coverage of others' positive or negative behaviours (e.g., volunteering vs. stockpiling) impacts collective identity and adherence to preventative measures. The second strand uses interview and survey methods to understand why people join emergent mutual aid groups, the effects of participation upon efficacy and well-being, and how such groups can be sustained over time. The third strand uses ethnographic interviews to examine the UK's security and civil contingency response to the pandemic and enforcement data to understand how responder actions impact upon community relations, adherence and social tensions.",2020,-99,University of Sussex,705242.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication, +C01102,ES/V00591X/1,Covid -19; Cancer attitudes and Behaviour Study,"Background: The impact of COVID-19 on UK public attitudes towards cancer is likely to be considerable, translating in to impact on the NHS from delayed referrals, missed screening and later-stage cancer diagnosis. Aim: To generate rapid evidence based on public views/response, informaing public health interventions to encourage timely symptom presentation, screening engagement and cancer- related health behaviours in the wake of the panedmic. Design: Prospective mixed-methods cohort study in the UK population. Methods: During June-August 2020, and again six months later, we will conduct a UK-Wide population survey of adults aged 18+ measuring attitudes and behaviour in the domains of cancer symptom presentation, screening, smoking, alcohol, diet and physical activity. We will sample from established online cohorts, supplemented with social media recruitment. Qualitative interviews will be conducted with survey participants to understand the contextual influences on cancer attitudes and behaviour. Using existing linked data, we will assess primary care referrals and investigations for suspected cancer symptoms, screening, smoking cessation and number/stage of new cancers diagnosed in the Welsh cohort. Analysis: Multivariable modelling will be used to assess determinants of symptom presentation (primary analysis), screening and health behaviours, and to identify longitudinal predictors of health service use and cancer outcomes. Qualitative data will be analysed thematically, with triangulation of data sources. Outputs: We will provide rapid recommendations to drive tailored public health initiatives for cancer early detection and prevention in the pandemic recovery period. Longer-term, the study will lay the foundations for assessing policy impact in response to future global health threats.",2020,-99,Cardiff University,677121.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery, +C01103,ES/V005073/1,Covid-19 and councils' finances: understanding risks and impacts & improving policy,"Councils are on the front line of the coronavirus crisis, being responsible for key services like social care and homelessness prevention and facing revenues falling due to lockdown. Government has provided them with billions of additional funding, but more may be required. A key challenge is ensuring this is allocated appropriately. Without such targeting, either more than is needed across the sector has to be provided or the most exposed and least resilient councils could run out of money or be unable to maintain services. Councils also need to understand how their residents are being differentially affected by the crisis. To help address these issues, we will analyse: 1. A suite of ex-ante indicators of the population and financial risks facing different English councils and their potential financial resilience, and publish the compiled data: 2. Actual changes in residents' incomes and spending, council tax payments and problems, and benefit claims by local area across the UK, which will provide evidence on how key risks are crystallising; 3. How different English councils' spending and revenues are changing during the course of the crisis, and the extent to which this corresponds to the aforementioned ex-ante and real-time indicators; We are having frequent discussions with central and local government, and the new research proposed here would directly feed into this - and inform wider public and political debate -, allowing us to help policymakers ensure councils have the funding and flexibility so that vital services can continue to operate and meet new demands",2020,-99,Institute for Fiscal Studies,86887.55,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts, +C01104,ES/V005464/1,"Nature Engagement and Wellbeing Pre-, During and Post Covid-19: Supporting the UK (Green) Recovery","On 23 March, the UK went into lockdown in response to the Covid-19 threat. As a result, people's engagement with natural environments may have changed significantly which is likely to have had significant impact on their wellbeing. We will work with Natural England to understand changes in nature engagement and wellbeing in the UK before, during and after lockdown and help understand what Government and Statutory Bodies can do to ameliorate the impact of Covid-19 on wellbeing now and as part of the UK Government Green Recovery strategy from Covid-19. We will examine what lessons can be learned from this period of disruption for theory development and practice, and for the provision and management of natural places for human wellbeing by: 1) providing an in depth understanding of how wellbeing during and post lock-down has changed across the UK as a result of changes in access to- and engagement with different natural environments. 2) creating a mapping of different wellbeing outcomes associated with different types of natural environments and the use of these environments for different activities. 3) contributing to theory development through improving the measurement and examination of a key concept in nature-wellbeing studies ""a sense of being away"". Four studies will be conducted analysing data on nature-engagement and wellbeing in: (1) a longitudinal survey study with a representative sample of (1500) UK households (June 2020-21) studying (changes in) wellbeing and engagement with different natural environments, (2) an analysis of social media images and comments posted during lockdown, (3) an ethnographic study with up to 30 families from different socio-demographic backgrounds to provide an in-depth insight into experiences during and post lockdown, and (4) secondary data analyses of data collected by Natural England over the last ten years to provide a broad perspective of nature engagement pre-, during and post lockdown.",2020,2021,University of Surrey,267870.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C01105,ES/V005898/1,Assessing policy to address the medium-run impact of COVID-19 on income and health inequality with models informed by the history of disease outbreaks,"This research aims to inform policy by assessing interventions to mitigate the medium-run implications of COVID-19 on income and health inequality. The uniqueness of our work is that we will develop models to predict inequalities that are consistent with medium-run historical postoutbreak dynamics in a large city, Glasgow, demonstrating similar inequalities to those seen across the UK today. The medium run is important because impacts of COVID-19 for inequalities are expected to persist for many years. Assessing mitigation policies requires models that can correctly predict the evolution of income and health distributions many years after an outbreak. To achieve this, we need to combine models typically applied to modern datasets with quantitative data from historical periods that, unlike contemporary data, cover sufficiently extended post-outbreak periods. Records have been especially high quality in Glasgow since the last quarter of the 19th century, covering a period of intense and volatile economic activity, and multiple disease outbreaks. Building on team expertise, we will: (1) construct mathematical models that predict income and health inequality after disease outbreaks; (2) compile quantitative historical data alongside contemporary datasets that capture the pre-COVID-19 situation for calibration and validation; and (3) assess the effects of policies relating to e.g. tax and benefits, upskilling subsidies, and diseasespecific or general health service provision. Our framework will allow us to assess policy interventions conditional on socioeconomic and health characteristics such as health status, professional class and income position, thus providing fine-grained results for economic and public health policy advisers nationally and locally.",2020,-99,University of Glasgow,281038.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts | Economic impacts, +C01106,ES/V008072/1,Rescuing a `Sick' Labour Market: Using Online Vacancy Data to Track COVID-19's Economic Impact.,"The outbreak of COVID-19 pandemic is likely to cause the worst recession the world economy has experienced since the Great Depression. Millions of people have already lost their jobs, and the functioning of the labour market has been profoundly disrupted by social distancing measures. In this context, it is fundamental to quantify the impact of the pandemic on job creation. This project will use a unique data set of daily online job postings to provide answers to key questions: which firms and sectors are expanding or contracting during the pandemic? Which jobs are being demanded? What skills and tasks are required in these jobs and how are work activities being delivered? How fast will the dynamics of job creation change as lockdown measures are eased? To answer these questions, our project will carry out an articulated analysis, employing multiple econometric techniques. Firstly, we will provide a detailed descriptive analysis on the evolution of job creation across occupations, sectors, and regions in order to deliver essential insights on the economic consequences of the pandemic, including the crucial distributive impacts across regions and types of jobs. Second, we will make use of advanced techniques in text analysis to study the wording of job postings in order to shed light on whether and how the structure of jobs changes as a result of the COVID-19 shock. In light of the intensity of the COVID-19 induced economic disruption, we may expect to see persistent structural changes to the design of work activities and the remuneration patterns associated with different jobs. The granular and high frequency data that we will employ will allow us to comprehensively assess the occurrence and importance of such changes. Finally, we plan to identify the firm-level characteristics that play a crucial role in ensuring firms' production continuity, and labour demand resilience. Among other factors, the degree of automated work may be crucial to ensure firms' production continuity under lockdown restrictions. For example, robots assembling product components or production processes that are compatible with remote work may allow firms to remain more active while social distancing measures are in place. Coupled with a detailed analysis on the skills demanded, the study will be provide essential inputs for the design and roll-out of targeted interventions that support the most severely affected areas, jobs and industries. These inputs will also be useful for the informing longer run investment decisions on skill training programs and government assistance.",2020,-99,University of Warwick,104195.61,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01107,ES/V005197/1,COVID-19: Developing evidence-based messages to encourage preventive health behaviours,"The likelihood of someone undertaking a health behaviour, following a public health message, is partly determined by how that message is framed. Therefore, if we wish to design a brief, effective public health message to encourage preventive behaviours, we must identify the specific determinants and moderators of these behaviours. We will provide this information by conducting a systematic review of the determinants of behaviours (such as handwashing and social distancing) that aim to prevent the spread of communicable illnesses. To enhance the appropriateness of the findings, we will only include research about communicable illnesses that are transmitted in a similar way and have similar symptoms to COVID-19. These illnesses include severe acute respiratory syndrome, H1N1 influenza and other types of flu. We will also include any relevant evidence about COVID-19 that emerges. The systematic review will follow the guidance on Conducting Systematic Reviews and Meta-analyses of Observational Studies of Etiology (COSMOS-E) and Cochrane guidance for COVID-19 rapid reviews and will include the following stages: electronic literature search; eligibility assessment; quality assessment; data extraction and synthesis; dissemination of findings. The research team have the necessary expertise and experience to carry out this review and disseminate its findings. Through this project, we will identify the most important variables to be addressed in public health messages and disseminate these findings to public health bodies. Therefore, the project will help to optimise the effectiveness of any messages designed to encourage preventive behaviours for COVID-19 or any future similar situations, thereby serving to minimise contagion.",2020,-99,Queen?s University Belfast,109860.67,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C01108,ES/V007610/1,COVID-19 and VCSE organisations response,"According to a recent government report (DCMS 06/05/2020) the Voluntary Community and Social Enterprise (VCSE) sector is ""fighting for survival"", with increased demand for its services, whilst simultaneously facing funding cuts estimated at £4.3bn (during March-May 2020), resulting in many VCSEs organisations estimated to be insolvent 'within weeks'. As the report states: ""Social distancing is making delivering services harder and more costly. Reserves are running out. Smaller charities, in particular, are at risk of imminent closure"". The core ideas for this project emerged through dialogue with DCMS, who are leading the government's response on how COVID-19 is impacting the sector, and co-designed with NCVO, the sector's leading infrastructure organisation. The project has three purposes. First, to provide realtime data and learning on how COVID-19 is impacting the whole sector and, significantly, varies across different organisations by size, structure and services offered. Second, to provide lessonslearned reports about how organisations on the impacts and responses to COVID-19, particularly focusing on the new working-practices and innovations which can be scaled across the UK. Third, to provide insights to aid long-term the VCSE sector's resilience. The project team brings a unique alignment of researchers specialising in the VCSE sector, HR and innovation, NCVO, who provide sector knowledge, guidance and access, through their research and policy team and 15,000 members. The outputs are a VCSE vulnerability barometer, providing real-time data of the impact COVID-19 on the sector, lessons-learned reports, enabling innovations to be scaled, a final project report and toolkit for resilience.",2020,-99,Nottingham Trent University,420036.46,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01109,ES/V004441/1,Covid-19 international comparative research and rapid knowledge exchange hub on diagnostic testing systems,"The proposed research asks how leading countries such as Germany and South Korea configure and use their national diagnostic testing systems for Covid-19 ('testing systems') in order to have relatively low rates of Covid-19 mortality per capita in their populations, to avoid or shorten 'lock-downs', and reduce economic impacts. We will identify the key elements of testing systems that have contributed to effective performance, including measures taken that have facilitated preparedness and resilience before the crisis, as well as those rapid innovations that have helped countries to deal with a fast evolving pandemic. We will explain how testing systems have been used, and how challenges related to testing have been overcome. The research will include the four nations of the UK and five further countries. Additionally, the role of transnational organisations such as the WHO, EU and large diagnostics companies will be studied to understand how tensions have been managed between increasing the quantity of new tests for Covid-19 and maintaining their quality. The project will establish a UK research and knowledge exchange hub to will facilitate dialogue between the international research team and policy makers so that relevant questions are rapidly addressed and lessons are disseminated to policy makers and public audiences, in the UK, and beyond. In order to support COVID-19 responses deliverables will be shared from the early stages of this 12 month project. Additionally to inform preparations for future outbreaks, we will contribute to national and international fora seeking to learn lessons from the current crisis.",2020,2020,University of Sussex,255407.41,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | Germany | South Korea,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C01110,ES/S002588/1,ESRC Mental Health Research Network,"The Covid-19 Social Study is a panel study of the psychological and social experiences of adults in the UK during the outbreak of the novel coronavirus run by University College London. Over 75,000 people are currently participating in the study, completing weekly online surveys about their experiences and behaviours. www.MARCHNetwork.org/research",2020,2020,University College London,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01111,ES/P010385/1,"Measuring the Impact of Brexit/Covid-19 on UK Investment, Sales and Productivity","Researching impact of COVID-19 via ongoing Decision Maker Panel on sales, employment, capital and requirements/availability of credit, working patterns, non-labour inputs, business expectations.",2020,2021,University of Nottingham,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01112,ES/T00164X/1,Productivity Insights Network,"We have secured a contract with Edward Elgar Publishing Ltd to produce a book entitled ""Productivity and the Pandemic: The Way Forward"". The book will be close to 100,000 words and will comprise some twenty chapters discussing the potential impacts of the coronavirus crisis on different aspects of the UK economy.",2020,2020,University of Sheffield,,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01113,ES/S009809/1,Trust and Trustworthiness in National and Global Governance,"An online national survey in the UK, US and Italy which includes questions 9 on COVID and political trust. Focus groups exploring political trust in towns and cities relating to COVID.",2020,2022,University of Southampton,,Human Populations,Unspecified,Unspecified,Suburban Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom,United Kingdom | United States of America | Italy,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues in Governance | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Policy research and interventions",2020 +C01114,ES/P008852/1,UK Collaborative Centre for Housing Evidence,We are running an internal project for circa 15 months that will examine up to 6 theme areas of housing related policies introduced during lockdown and following what happens to those policies post crisis and into recovery.,2020,2021,University of Glasgow,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",,2020 +C01115,ES/S009965/1,Life with Corona,"IDS, ISDC and UNU-WIDER collecting real time data on the coronavirus and its social and economic impacts, to build a global knowledge base about how people are dealing with the epidemic (including on focus on trust, which was key in the response to the Ebola).",2020,2022,Institute of Development Studies,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C01116,ES/S012648/1,Practices and Combinations of Practices for Health and Wellbeing at Work,Collecting data on how occupational health and wellbeing services are adjusting through a longitudinal case study.,2020,2020,University of East Anglia,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C01117,ES/S015671/1,British Election Study,"Wave 20 of the BES internet panel will ask questions on COVID-19 and its impact on political opinion including exposure (individual and family), evaluations/handling and impact on issue position and salience.",2020,2023,University of Manchester,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",,2019 +C01118,ES/S012486/1,Young graduates' engagement in new training,To what extent have young graduates engaged in new training as a result of the impact of the pandemic on the jobs' market.,2020,2020,"Research Centre on MicroSocial Change (MiSoC), University of Essex",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01121,ES/R00384X/1,Wales Centre for Public Policy,"Briefing papers on promoting a Green Recovery, supporting the groups hit hardest by recession, impact on public services.",2020,2020,"Economic and Social Research Council, Welsh Government, Cardiff University",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom | United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C01122,ES/P008003/1,RELIEF Centre,"The Future Education team of the RELIEF Centre have started a collaboration with the Lebanese University (LU) to develop a massive online open course (MOOC) focused on remote learning, framed within the context of the COVID-19 pandemic but also applicable to other contexts. The team is conducting research via the MOOC, which already has over 14,000 enrolments, to find out about teachers' experiences and RELIEF Centre partner, the Centre for Lebanese Studies (CLS), are also doing research with links from the MOOC to surveys on teachers', learners' and parents' experiences in Lebanon during the pandemic and the lockdown situation associated with it.",2020,-99,University College London,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01123,ES/S012435/1,WISERD,"All workpackages are reviewing their capacity to address Covid19 within the WISERD research programme. The following work is currently being taken forward: (i) we will undertake an Email survey of academics across the Children's Worlds network (an international study of 41 countries measuring subjective children's wellbeing, rights and participation). This aims to ascertain their views about the impact on children, how they have been positioned by decision makers and their role/influence in decision making in their respective countries. (ii) we will undertake follow-up interviews with 10-12 families in South Wales who we originally interviewed in the previous Centre's work on intergenerational transmission of civil society across three generations; children, parents and grandparents. These follow up interviews are to consider how families have responded and adapted to COVID-19 in relation to their family relationships and attitudes towards civil society. (iii) we are designing a new sweep of the WISERDEducation Multi Cohort Study (WMCS) that will collect data from our existing cohort of young people (c1,200) from across 13 secondary schools in Wales (two cohorts, one in Year 8 and one in Year 10). These questions will be about how they are managing during the lockdown, what their daily activities look like, what home learning looks like, how they view their rights during the lockdown, and activities and attitudes towards civil society following the pandemic. (iv) we will apply accessibility models in relation to health patterns in Wales. A study looking at spatial inequalities in access to residential care homes in Wales based on Care Inspectorate Wales data will be followed up with a more detailed case study in the area covered by the Regional Partnership Board in West Wales with colleagues in Ceredigion and Carmarthenshire. (v) our research on human rights and the mixed economies of welfare is being re-focused to look across the 4 UK jurisdictions at how the legal and policy context related to third sector adult social care provision has changed in light of corona virus and what has been the reaction of third sector care providers and what impact have the changes had on their work. (vi) our planned work on civil society, and placed based strategies for sustainable development is being re-focused on the role of City Regions and place based polices in supporting and renewing local economies in the aftermath of Covid 19. (vii) our work on platforms and capabilities is being refocused to explore the impact of economic and social changes arising from Covid19 on Foundational Sectors (including food delivery and social care).",2020,2024,Cardiff University,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C01124,ES/L003945/1,What Works Centre for Local Economic Growth,Research on the evidence to help places rebuild their economies and identify the leading indicators that might help them understand the impact of the pandemic on different areas.,2020,2020,London School of Economics and Political Science,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01125,ES/P008976/1,Network for Integrated Behavioural Science,Multiple projects including work on the impact (and possible unintended consequence of) messages to promote conformity with social distance recommendation and developing an experimental design to measure people's perceptions of when people would consider using NHS services.,2020,2020,University of Nottingham,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C01126,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),Research and working paper on increase in Google searches indicative of anxieties and economic fears.,2020,-99,University of Warwick,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +C01127,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),Application of a phenological model for forecasting the development of COVID-19 cases in Italy and the UK. Daily comment and analysis of Italian data by Facebook post.,2020,-99,University of Warwick,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C01128,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),Analysis of movement of migrant workers and the spread of coronavirus to rural areas where healthcare capacity is low.,2020,-99,University of Warwick,,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C01130,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),"We study the effects of news coverage of the novel coronavirus by the two most widely-viewed cable news shows in the United States - Hannity and Tucker Carlson Tonight, both on Fox News - on viewers' behavior and downstream health outcomes.",2020,-99,University of Warwick,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C01131,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),The team is working with the Swedish government (existing partnership with the local public employment service) to assess the impact of the COVID-19 crisis on the labour market.,2020,-99,University of Warwick,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01132,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),"Research on policies to rebuild government finances: personal income and capital gains taxation, based on HMRC Datalab data; net wealth taxation measuring UK wealth using tax data.",2020,-99,University of Warwick,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01133,ES/L011719/1,CAGE Research Centre (Centre for Competitive Advantage in the Global Economy),"Research on the labour market implications of the 1918 India influenza epidemic, and drawing out lessons for the current pandemic.",2020,-99,University of Warwick,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01134,ES/M001660/1,Centre for Longitudinal Studies,"A nationwide survey of the participants of five national longitudinal cohort studies, to examine the impact of the pandemic, help understand how people at different life stages are affected, and how prior life experiences shape resilience or vulnerability.",2020,2021,University College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01135,ES/M010163/1,Centre for the Understanding of Sustainable Prosperity (CUSP),Looking at the implications for access to finance for small business in the crisis.,2020,2020,Middlesex University London,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01136,ES/M010163/1,Centre for the Understanding of Sustainable Prosperity (CUSP),"New work is being developed with Marit Hammond and Brian Doherty, working with CUSP Fellows Graham Smith, Graham Hayes, and Clare Saunders, collaborating with Extinction Rebellion (XR) on the role of XR pre, during and post COVID.",2020,2020,Keele University,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",,2020 +C01137,ES/M010163/1,Centre for the Understanding of Sustainable Prosperity (CUSP),"With Aldersgate Group we are working on inputs to the emerging discussions on a green recovery in the UK. Through the Club of Rome (of which Director Tim Jackson is a member) we are working on similar themes in the context of the EU (Tim was in a virtual meeting with Frans Timmermans - the executive vice-president of the Commission for instance). We are feeding (sensitively) into the media discussions around implications, recovery, lifestyles, work and so on. And we have initiated some specific bits of work which expand and extend our research programme in response to the crisis. For example, with Aldersgate Group we are looking at some input-output analysis (drawing on our existing work) that could identify jobs-rich green recovery options. We are also doing a piece of econometric work on the antecedents of COVID-19 mortality rates, trying in particular to understand the rather large differences in mortality rate between countries. (This project is part funded by some internal funds that we have been able to leverage - actually from before the crisis, but it involves one of our part-CUSP-funded researchers.)",2020,2020,University of Surrey,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01140,ES/T001364/1,Supporting Adult Social Care Innovation,"Researching adult social care, how adult social care organisations are engaging with the NHS and changes in care delivery during the pandemic.",2020,2020,London School of Economics and Political Science,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01142,ES/L011840/1,Consumer Data Research Centre (CDRC),"Prof. Alex Singleton, Jacob MacDonald and Alessia Calafiore at University of Liverpool has completed a review looking at the impact of changes in mobility patterns as a result of lockdown and how this has impacted air pollution (Decomposing Daily Regional Pollution and Human Mobility Patterns Under UK COVID-19 Stay-at-Home). This work explores the relationship between combustion-based pollution (NO, NO2, NOx) and the relative space-time signature of human mobility patterns under the lens of the recent global COVID-19 pandemic. With mass stay-at-home orders enacted, the movement patterns in and around local points of interest have changed - bringing with it changes in transportation mode use and frequency, among other things. The nature of this shift has led to significant drops in regional pollution levels across the UK, yet quantifying the varying contributions from different human activities to this decrease is challenged by the complexity of pollution patterns across different dimensions.",2020,-99,University of Liverpool,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01143,ES/L011840/1,Consumer Data Research Centre (CDRC),"Oliver O'Brien (Data Scientist, CDRC, UCL) has completed some analysis looking at the impact Covid-19 and the lockdown have had on bicycle sharing schemes usage. This has been reported on the front page of the FT (1st May) and was also presented by Oliver to an audience of 100+ at a public forum Cycling@Tea-Time seminar, hosted by University of Westminster Active Travel Academy (https://register.gotowebinar.com/register/2567905415169655822). This session was chaired by Tom Cohen, recently a director at the UCL Institute for Transport Studies. See also https://oobrien.com/2020/05/lockdown-and-bikeshare/ and https://twitter.com/oobr/status/1256196681579798531.",2020,-99,University College London,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01144,ES/P008313/1,Optimising antibiotic use along surgical pathways: addressing antimicrobial resistance and improving clinical outcomes,"Data being collected on affects of covid-19 at partner hospital sites in Kerala, India and Cape Town, South Africa.",2020,-99,Imperial College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | South-East Asia,,,,United Kingdom,India | South Africa,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01146,ES/P008224/1,Understanding and improving antimicrobial prescribing in care homes: a multidisciplinary approach,Working with care home staff on COVID-19 including an in-depth case study and a survey of care home staff and GPs who prescribe for care home residents.,2020,2020,University of Dundee,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C01147,ES/M010236/1,"Human Rights, Big Data and Technology Project","We are currently applying and developing our existing research to address the human rights implications of the use of new and emerging technologies during the pandemic. Current work includes: 1) the human rights implications of contact tracing apps 2) the impact of the digital divide, particularly in relation to the rights to education and health and groups in positions of vulnerability (including older persons and violence in the home) 3) the use of algorithms to support health-care decisions, including prioritisation of resource 4) disinformation (both health disinformation and in blaming and scapegoating particular groups for the spread of COVID-19) We are in the early stages of developing further research on policing and refugee protection.",2020,2021,University of Essex,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making | Communication,2020 +C01148,ESRCCOVID063,"Post COVID-19, what will be the 'new normal' energy demand in buildings?","Since September 2019, 1,700 bill payers have agreed to share for research purposes, their half hourly gas and electricity smart meter data with SERL. This data will be combined with a COVID-19  questionnaire about changes to occupant energy using behaviours during the lockdown and subsequent energy use surveys while a 'new normal' is established.",2020,-99,Sustainable Energy Research Lab and the Centre for Research on Energy Demand,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",, +C01149,ESRCCOVID033,ADR Wales,"The Welsh Government, data research centres and the NHS have quickly created a cross-institutional team to provide timely evidence to inform policy and practice to tackle the epidemic and its impact in Wales, of which ADR Wales is a part. The team has come together to leverage existing and new datasets and apply their expertise to provide evidence to reduce the impact of the epidemic on the Welsh population using the SAIL Databank, an ADR Wales partner.",2020,-99,Swansea University Welsh Government,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C01150,ESRCCOVID034,ADR Scotland,"Roger Halliday, Chief Statistician and ADR Scotland Co-Director, sits on the Scottish Government Covid-19 Advisory Group. This Group has set up a Data Task Force, which is chaired by Roger and includes in its membership ADR Scotland's other director, Professor Chris Dibben, as well as other members of the partnership. The purpose of the taskforce is to enable evidence-based policy and operational decisions by organisations in Scotland responding to the current Covid-19 situation. For more information about accessing this data, please visit ResearchData.Scot.",2020,-99,Scottish Government Edinburgh University,,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions, +C01151,ESRCCOVID035,ADR UK investment into ONS,"Three new Covid-19 datasets have been made available in the ONS Secure Research Service (SRS). In addition, ONS is jointly leading the government's large-scale virus infection and antibody test study, for which the SRS, which receives funding from ADR UK, is hosting the data and analysis.",2020,-99,ONS,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C01152,ESRCCOVID036,ADR Northern Ireland,"In Northern Ireland, Northern Ireland Statistics and Research Agency (NISRA) researchers have been assisting in the production and continuous development of official weekly deaths statistics, recently supplemented with specific analysis of Covid-19 related deaths. They are investigating how data linkage opportunities may broaden the existing evidence base to support decision making related to Covid-19, as well as the impact Covid-19 is having on society.",2020,-99,NISRA Queens University Belfast,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Ireland,Ireland,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Policy research and interventions | Other secondary impacts, +C01153,ES/V004883/1,COVID-19 (Mis)Information Exposure and Messaging Effects in the United Kingdom,"This project will examine four specific research questions about COVID-19 information and beliefs. 1. How (mis)informed is the public about the COVID-19 pandemic? 2. In this time of crisis, are people making sense of the world through widespread adoption of conspiracy theories? 3. What is the quality of COVID-19-related information on the internet that is actually consumed by people? 4. Can inaccurate information and conspiracy thinking be effectively countered by informational interventions? Each component of the project will seek to increase our scientific understanding of information consumption and belief updating about science, health, and other controversial subjects while also generating practical, real-world recommendations that will help policymakers, journalists, and science communicators to design policies and deliver information that will help stop the pandemic. By combining a multi-wave survey experiment with a large enough sample to examine highly affected areas (e.g., West Midlands) and behavioural exposure data, this study will provide the most systematic measurement to date of (1) the accuracy of the COVID-related beliefs about public health and public policy; (2) the prevalence of health and policy misconceptions related to COVID-19 and the correlates of those misconceptions; (3) the prevalence of exposure to both highquality and untrustworthy information about COVID-19, including the most important sources of (mis)information and the correlates of consumption of both types of information; and (4) the effectiveness of corrective information in combating COVID-related misconceptions.",2020,-99,University of Exeter,339978.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C01154,ES/V004964/1,Identifying and mitigating the individual and dyadic impact of COVID19 and life under physical distancing on people with dementia and carers (INCLUDE),"People with dementia say that personal contact is key to their well-being, while many family members providing unpaid care are isolated and feel lonely. People with dementia and the family members who care for them are especially vulnerable to the impact of the physical distancing measures needed to reduce the risk of developing coronavirus (Covid-19) symptoms. These measures can be frightening and can damage well-being and relationships, while reducing accessibility of care services and support. With social restrictions continuing for an extended period, people affected by dementia risk being 'left behind' as the rest of the population adapts. Our approach to delivering high-quality care and support for people affected by dementia must change to take account of this. In the INCLUDE study we aim to understand the impact of the Covid-19 epidemic and the resulting restrictions on people with dementia and their carers, and to develop resources to address the negative and potentially harmful effects of this situation. We will invite people with dementia and carers participating in the ongoing 'Improving the experience of Dementia and Enhancing Active Life' (IDEAL) programme to take part in INCLUDE. IDEAL has been following a large group of people with dementia and carers over time to understand what makes it possible for people to 'live well' with the condition. The findings highlight the importance of the very social and psychological resources that are most likely to have been affected by the Covid-19 epidemic. The INCLUDE study will add a new data collection module to the IDEAL programme. This will be specifically designed to examine the impact of the Covid-19 epidemic and resulting restrictions. Participants will complete questionnaires and respond to open-ended questions in a structured interview, and a sub-set will additionally engage in a more conversational semi-structured interview about their experiences. People with dementia and carers will be involved in developing the interview schedules. We expect 300 people with dementia and 300 carers to complete the structured interview, with up to 50 people with dementia and 50 carers completing the semi-structured interview. The information that INCLUDE participants provide will enable us to understand how Covid-19 has affected people with dementia and carers as a whole and how the impact differs for particular sub-groups, for example based on age, type of dementia, or socioeconomic status. Because we already have a good deal of information about IDEAL participants we will be able to link their responses with information they provided previously. This will allow us to identify the impact of Covid-19 on trajectories of symptoms and well-being; for example, we can pinpoint where changes over time in particular symptoms are greater than expected. We will also explore the ways in which changes for the person with dementia affect the carer and vice versa. Working together with people with dementia and carers, we will use the evidence gained to develop the Living Well Alongside Coronavirus (LILAC) toolkit, a set of resources to support social, mental and physical health and relationships for people with dementia and carers, and provide guidance for health, social care and voluntary sector staff.",2020,-99,University of Exeter,728738.61,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01155,ES/V004980/1,COVID-19: Human Rights Implications of Digital Certificates for Health Status Verification,"The UK government announced it would consider establishing ""immunity passports"" as part of a lockdown exit strategy during the ongoing outbreak of COVID-19. Digital certificates for verifying immunity, proof of vaccination and COVID-19 test results may contribute to the long-term COVID-19 management strategy, whereby based on their health status, certain individuals would be able to return to work and enjoy their general freedom of movement. Yet, such certificates pose important questions for the protection of data privacy and human rights, given that they would (1) use sensitive personal health information, (2) create a new distinction between individuals based on their health status, and (3) be used to determine the degree of freedoms and rights one may enjoy. The technologies adopted during the current pandemic will have a lasting impact on our societies. They will shape how we respond to the trade-offs between data privacy, human rights, and public health interests. This project will evaluate whether and how digital certificates for health status affect our enjoyment of data privacy and the protection of our human rights, assessing whether there are effective ways to mitigate any potential risks for these rights, thus informing decision-making in this area of crucial national interest.",2020,-99,University of Exeter,121122.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures, +C01156,ES/V005006/1,"Gemini COVID-19 study: Immediate and longer-term impacts on the health, behaviour and wellbeing of U.K. families","The impact of the COVID-19 pandemic on U.K. families goes far beyond the devastating health implications of the virus itself. Added family stresses, including income loss, excessive confinement, social isolation and anxieties about health and education heighten pressure and volatility within the home. Children are among the most vulnerable in society. Changes to the home environment, where families are now spending virtually all of their time, are unprecedented. Children are increasingly reliant on digital devices, opportunities for physical activity have greatly diminished and the home-food environment has been impacted by disruptions to availability and accessibility. Collecting information on the effect of the COVID-19 pandemic on the home environment, and the consequences for children's physical and mental health is an immediate priority. The Gemini study is an established nationally representative twin birth cohort which has been collecting detailed information about the twins and their families for the past 13 years. Gemini offers a unique opportunity because in the five months prior to U.K. 'lockdown', the study collected detailed information on the food, physical activity and media environments within the home, along with measures of health behaviours and psychological wellbeing. This timely and comprehensive baseline data can be combined with extensive information collected during the COVID-19 crisis and its aftermath, enabling rapid characterisation of the impact of the pandemic on the family environment and child health. The immediate insights gained from this study will inform evidence-based guidance for how best to respond to the current pandemic to mitigate negative impacts for families, while simultaneously shaping policies to promote child health and wellbeing should future waves of infection emerge.",2020,-99,University of Leeds,151609.35,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01157,ESRCCOVID064,Safe Gaming: Developing Guidelines to Help Young People Engage Safely in Online Gaming during Covid-19,"The aim of this project is to co-design, with young people, academics, partners from the gaming industry, statutory and third sector organisations, evidence-based guidelines to better equip young people during Covid-19 and beyond engage with online gaming effectively, thus, maximising opportunities for using gaming to enhance their mental wellbeing.",2020,-99,London School of Economics and Political Science,8085.93,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01158,ESRCCOVID065,Ethical challenges for social workers during COVID-19: Resources for practice,"Internationally-relevant web-based guidance/case studies, assist social workers in crisis situations. Building on model of 'ethics work'/related concepts to develop guidance in ethical decision-making in times of crisis (specifically epidemics/ pandemics, but with wider relevance to working in disaster/war zones).",2020,2020,Durham University,5114.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues,Research to inform ethical issues in Clinical and Health System Decision-Making,2020 +C01159,ESRCCOVID066,Creating web resources to support early years settings with making Digital Stories for enabling transitions and assessments of autistic children,"This project was devised to strengthen and maintain existing research-practice relationship with early years settings under the ACoRNS [Autism Community Research Network @ Southampton] remit and apply the methodology of digital stories to support autistic children's transitions between nursery and primary school. In light of Covid19 and the closure of early years settings, the project team are adapting their activities in response to a request from Hampshire Local Authority. Their focus is now to provide new resources to help providers create Digital Stories during lockdown: 'we need Digital Stories more than ever before as traditional transitions are going to be difficult before the summer.'",2020,-99,University of Southampton,613.5,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01161,ESRCCOVID068,A literature review of the evidence for successful post-disaster interventions relating to: (i) schools; (ii) vulnerable children,The COVID-19 crisis is a unique situation but there have been many previous disasters that have resulted in school closures and created emotional difficulties for children (particularly those with vulnerabilities). This project will review the scientific literature on interventions that have followed previous disasters so that we can ensure local and central government follow the best possible evidence when attempting to mitigate the problems created by the COVID-19 crisis.,2020,2020,University of Leeds,2454,Human Populations | Other,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01162,ESRCCOVID069,Collecting school data on home learning provision and interactions with vulnerable children during the COVID-19 lockdown,"We are currently trying to get insights into the situation on the ground - and we are creating questionnaires to capture information from local communities. This project will help support our existing network of researchers (available as they have been removed from school testing duties) to communicate - remotely - with Headteachers and SENCOs to capture the success (or otherwise) of initiatives to support vulnerable children and home learning. We will then be able to link existing routine data sets within the Connected Bradford project around health, education and crime etc). This work will provide much needed information to the local government and the Department for Education to inform their understanding of the National picture.",2020,2020,University of Leeds,2269.95,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01163,ESRCCOVID070,"Forced migration, sexual and gender based violence and COVID-19",Shaping policy and practice about how to ameliorate the multiple effects of COVID-19 on forced migrant sexual and gender-based violence survivors and the organisations that support them.,2020,-99,University of Birmingham,6061.38,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01164,ESRCCOVID071,Optimising Social Media for Physical Activity and Nutrition during COVID-19,"To provide evidence-based guidance to support the health-related uses of social media, to inform the design of effective policy and practice to optimise the educative potential of social media for physical activity and diet during a global pandemic and beyond.",2020,2020,London School of Economics and Political Science,10649.13,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01165,ESRCCOVID072,COVID-19: Work-Life Balance and the Pandemic,"Researchers at the University of Leicester are conducting research (a survey and diary study) examining the effects of new ways of working instituted in response to the COVID-19 outbreak. The funding supports data analysis and subsequent engagement with policy makers, unions and professional bodies representing employees to take forward findings and shape future policy and practice.",2020,-99,University of Leicester,6049.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01166,ESRCCOVID073,Covid-19 Rapid Response Fund (call for impact projects),To provide support for rapid impact projects (up to £3k) each that can be carried out immediately and provide a social science response to the pandemic. 7 projects funded so far.,2020,2020,Queen?s University Belfast,49080,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Ireland,Ireland,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01167,ESRCCOVID074,Recovering from/Adapting to life after lockdown Fund (call for impact projects),"To draw on social science insights to respond to the ""next phase"" of the pandemic, and recovery/adaption for communities, the economy, healthcare systems etc. Will fund projects up to £10k.",2020,2020,Queen?s University Belfast,73620,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Ireland,Ireland,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Economic impacts,2020 +C01168,ES/V008781/1,Addressing inclusivity in the spatial and social impacts of COVID-19 on the self-employed in the UK,"The self-employed are a particularly vulnerable group in this current crisis. In contrast to elsewhere, the UK has seen significant growth in self-employment, now reaching 15% of the workforce. They are predominant in those sectors most hit by shutdown and social distancing measures. This disproportionate impact on self-employment is likely to have a longer-term effect on entrepreneurial activity and regional economic performance in the UK if current policies are not able to support groups and areas that are particularly hit. Self-employment has specific social and spatial features which means that the crisis will impact on specific social groups and areas in the UK differently. Women and some ethnic groups cluster in the most affected sectors, and some regions, particularly in the North and Scotland, have large shares of self-employment in accommodation and food services. Although generous to those eligible, government support (SEISS) excludes some significant groups. We will investigate the disparate spatial and social impacts of COVID-19 on the self-employed. We will undertake 1) quantitative secondary analysis of major UK datasets in order to provide a robust understanding of differential impacts on self-employment. This will be complemented by 2a) qualitative research involving an expert panel, to provide contextualisation and aid rapid impact such as policy and practice advice, and 2b) interviews with the self-employed to understand personal perspectives and effectiveness of policy. We will provide evidence and understanding to inform future support policies, for example within local industrial strategies, to ensure rapid and sustainable recovery in this group of workers.",2020,-99,University of Southampton,174766.52,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01169,ES/V009427/1,Psychosocial effects of the COVID-19 pandemic: Identifying mental health problems and supporting wellbeing in vulnerable children and families,"There is an urgent need to understand and mitigate the psychological and social impacts of the COVID-19 pandemic and associated lockdown on primary school children. This is especially important for those known to be vulnerable. Children with emotional, cognitive, developmental and social vulnerabilities can already be identified in primary schools. The mental health consequences of school closure, social isolation, increased financial and emotional stress, and greater exposure to family conflict are likely to be particularly pronounced for this high-risk group. Data from immediately prior to the pandemic are needed to provide robust assessments of the impact of COVID-19 on vulnerable children. This proposed study capitalises on an ongoing study of 300 primary school children (4-7 years) identified as ""at-risk"" for mental health problems by teachers. Our study collected rich social, cognitive and mental health data prior to the COVID-19 pandemic. Our aim is to re-assess this cohort, now aged 5 to 10 years, remotely, during the pandemic and again later in the academic year to evaluate the social and emotional impacts of COVID-19 and identify how negative consequences can be mitigated. We will also be able to assess longer term impacts because this cohort has consented to life-long health, social care and education record linkage. Understanding the immediate psychological and social consequences for vulnerable children and families is not only important for research; it is essential for rapid development of policies and interventions to mitigate the mental health problems and provide support to families during and after lockdown.",2020,-99,Cardiff University,503327.67,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C01170,ES/V009648/1,How is the COVID-19 accidental experiment around working from home changing the way the UK will work after lockdown?,"This research is designed to support economic recovery from the COVID-19 crisis, providing timely, actionable insight and recommendations about Working from Home (WfH), and the long-term implications of crisis-driven adaptations for organisational practice and policy responses. This proposal engages with three UKRI Research Questions: (1) how the pandemic has influenced different sectors in the UK; (2) the longer-term implications of WfH; and (3) which new behaviours and working practices will remain and which should be encouraged? A team of cross-institutional experts active in research related to WfH during lockdown, will employ a mixed-methods approach using an online survey, organisational case studies, and secondary analysis of national datasets. The research will explore both employer actions, practices and strategic decision-making, and employee experiences and outcomes of WfH during lockdown and its aftermath. Focusing on Professional Services and Public Administration, where access has been agreed in principle with employers in law and local government, a longitudinal perspective will contour and contextualise the recovery process in these sectors, selected for their contrasting business models, frontline pandemic response, and levels of WfH prior to the crisis-driven mass migration of white-collar workers into roles performed entirely from home. Our impact pathway will promote early engagement with findings: offering regular insight briefings on employee experience and outcomes; an employer summit that shares and shapes our assessment of whether WfH under the pandemic is activating wider changes in work organisation, job design, agility and flexibility; and a policy roundtable informing policy responses around 'good work' and flexible working.",2020,-99,University of Southampton,238629.41,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01171,ES/V009400/1,Carrying the work burden of the Covid-19 pandemic: working class women in the UK,"Working class women are carrying the burden of the extra physical and emotional labour being generated by the COVID-19 pandemic. These women care for children, sick and frail elderly, clean buildings, cook and serve food, administer institutions and staff shops, while retaining major responsibility for domestic work and caring at home. The Women's Budget Group (WBG) highlighted that 2.5 million of the 3.2 million workers employed in the highest risk roles during the pandemic are women, many in low-paid roles. There is little detailed attention to their experiences and needs and how to urgently support them in their essential work. The pandemic has created job loss, work instability, financial hardship and great insecurity. Working class women are heavily impacted (WBG 2020; Fawcett Society 2020). There has been time squeeze and work intensification for some, a desperate search for new jobs for others, alongside more unpaid care with school and nursery closures. What is not yet known is how working class women are responding in real time to the various, and as yet potentially unknown, pressures imposed by the virus. If they are unable to manage the existing and additional pressures placed upon them, workplaces, child and elder care will all be severely affected. The project is in collaboration with the WBG, the leading independent organisation that deals with the impact of policy on women's lives. We will analyse data from the ESRC's flagship 'UK Household Longitudinal Study', including vital new information being gathered on the impact of COVID-19. This will be a large nationally-representative study as the pandemic effects roll out over the next year. This project will deliver a significant contribution to the understanding of, and response to, the pandemic. It will rapidly fill an urgent need by identifying and responding to difficulties experienced by working class women in real time. With WBG, it will start to disseminate early findings and urgent policy solutions to employers, unions, government, key charities and lobby groups within two months of starting. This is crucial if working class women are to continue to carry the additional strain of increased work and home demands during the pandemic.",2020,-99,University of Nottingham,166498.99,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C01172,ES/V009508/1,Understanding the impacts of COVID-19 on the provision of NHS health care and patient outcomes,"We will provide a detailed description of the extent to which non-COVID-19 NHS activity has been affected by COVID-19, who is most affected, and how patient outcomes have changed. COVID-19 has led to enormous changes in the provision of NHS care. All non-urgent operations have been cancelled and a third of hospital beds converted for use by COVID-19 patients. A&E attendances dropped by 50% in the past month. This will have major impacts on care received by non-COVID-19 patients and their outcomes during and after the outbreak. However, who is affected and how this is likely to impact future health outcomes is currently unknown. We will quantify the reduction in NHS care, and examine its distribution by age, sex, ethnicity, deprivation and geography. We will analyse the latest information from Understanding Society and the English Longitudinal Study of Ageing to document disruptions to primary, hospital and community care across England, Scotland and Wales. This will complement analysis of real-time patient records from a large London hospital trust that builds a rich picture of disruptions to hospital care and changes in patient outcomes. This will provide detailed, timely and important evidence of the impacts of the pandemic on care provided to other patients. The research team has already engaged with key policymakers - including HM Treasury and DHSC - providing evidence on the impacts of COVID-19, and the related economic downturn, on patient health. This research will provide new empirical evidence to help allocate NHS resources to minimise risks to patient health.",2020,-99,Imperial College London,125214.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,Health Systems Research,Health service delivery | Health financing, +C01173,ES/V009389/1,Risk Sharing Mechanisms To Mitigate The Financial Consequences Of Pandemic Risk: Economic And Social Insurance Solutions For The UK,"The pandemic is causing business interruption (BI) across UK businesses, resulting in unprecedently widespread and global economic losses that are too large to be absorbed in full by the insurance industry. Yet, businesses are unlikely to obtain credit for trading without access to adequate BI insurance. As the government steps in to protect businesses, the burden for taxpayers is rising exponentially. This study will develop a novel risk-sharing mechanism to effectively share pandemic BI risk between UK businesses, insurers and government. We will conduct action research; a method where we work with partners to define the problem, act upon it, and embed actions in future learning. We have partnerships agreed with UK business, insurance industry and government stakeholders to develop a BI risk-sharing mechanism. We will evaluate and build upon short-term post-lockdown products being generated by insurers and develop new solutions with this full range of stakeholders. This will enable delivery of a sustainable longer-term governance and funding solution for supporting UK business against interruption from current and future pandemic. Our research team is perfectly equipped as we have studied risk-sharing mechanisms globally for catastrophic disasters, with our results influencing policy and practice. Our research process and policy recommendations will (i) segment pandemic BI risk into core (must-have) and additional (good-to-have) cover elements; (ii) identify who (business, insurance, or Government) should take which elements; (iii) propose a public-private governance and funding solution that combines different strategic responses to sharing BI risk elements across UK businesses, insurance industry and government stakeholders.",2020,-99,City University of London,156242.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C01174,ES/V009869/1,Meeting food vulnerability needs during COVID-19: applying a systems approach to evidence based policy and practice,"Working with national governments across the UK - including Defra's Food Vulnerability Directorate, the Scottish and Welsh governments and the Food Standards Agency, this project will apply a systems approach to enable understanding and monitoring of the array of activities to enhance or provide food access to vulnerable people during the COVID-19 outbreak, including both financial and direct access. Reflecting Defra's Food Vulnerability focus, target groups include people with low incomes, shielded individuals, and the 'non-shielded vulnerable'. The aims of this project are to: - Undertake comprehensive mapping of the food access systems, highlighting key areas of vulnerability within them and identifying links to other support systems. - Using a case study approach, develop and apply methods for monitoring and evaluating the food access for vulnerable groups during the COVID-19 outbreak and through the easement of lockdown restrictions. - Develop 'exit strategies' for managing the transition out of systems that will not be provided after the crisis. - Establish 'best practice' protocols for resiliency planning for the future. The project methods include collaborative systems mapping, local area case studies (collating qualitative and quantitative data) and in-depth interviews with system users and other key actors. The project will provide policymakers with a comprehensive overview of food access activities for vulnerable groups and identification of key gaps and weaknesses within this system, informed by stakeholders who use these systems and those contributing to them. Civil society and business communities benefit by directly informing this work, but also from its evaluative and monitoring components, enabling them to identify and refine their efforts in the wider context.",2020,2022,University of Sheffield,368223.93,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C01175,ES/V009877/1,Monitoring socioeconomic and mental health trajectories through the COVID-19 pandemic,"This study will use nationally representative data collected monthly by the UK Household Longitudinal Study's (UKHLS) questionnaire which gathers information on people's experiences during the period of the Covid-19 pandemic. This information will be used to assess the pandemic's ongoing impact on individuals' mental health and financial situation, and how this differs among subgroups of the UK population. By combining information within the Covid-19 questionnaire with baseline data collected in previous years as part of the UKHLS, we will be able to identify who has felt the deepest and the longest-lasting impact on their financial situation and their mental health, and how these two impacts are related. Data collected in April 2020 - when the pandemic was at its initial height in the UK - will allow us to identify the groups that were immediately hit by the initial shock to the UK economy and social distancing measures introduced. The research will use statistical modelling to identify the significant factors in explaining poor mental health and poor economic circumstances at the height of the pandemic in the UK as well as to identify groups at particular high risk. Subsequent monthly data will allow us to identify the rate and extent of the recovery of high risk groups. By examining individuals' personal characteristics and socioeconomic situation (including their exposure to schemes aimed at mitigating economic shocks) as well as their mental health and economic situation at each time point, we will be able to identify what personal factors and external interventions are associated with a fuller or quicker recovery, and which individuals remain vulnerable and require additional help and possibly policy interventions to recover.",2020,-99,NatCen Social Research,196270.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts, +C01176,ES/V009931/1,Identifying and mitigating the impact of COVID-19 on inequalities experienced by people from BAME backgrounds working in health and social care,"Black, Asian and minority ethnic (BAME) groups constitute 14 percent of the population in England and Wales. The NHS is the largest employer of BAME staff, comprising at least 20 percent of the workforce (45 percent in London). BAME healthcare staff, experience greater levels of workplace racism, harassment and discrimination than other staff. Discrimination, and bullying or abuse have persistent effects on mental health and occupational outcomes. Such workplace experiences (more commonly perpetrated by colleagues, managers than patients), have increased over the past five years, particularly in London NHS Trusts. BAME staff also have poorer working conditions (e.g., lower pay, less control in decision making, dis-empowered from complaining about working conditions). COVID-19 infections disproportionately affect BAME UK communities including healthcare workers (e.g., increased mortality among Black ethnic groups). Therefore, adverse working conditions faced by BAME NHS staff may be worsened by greater exposure to COVID-19 related disadvantages, within and outside of the workplace. These adversities place BAME staff in vulnerable positions (e.g. working in role that involve greater exposure to COVID-19 wards; heightened workplace stresses, stigma, fear and uncertainty around COVID-19 risks for themselves and their families). These ethnic inequalities must be addressed to avoid the social, economic, and moral costs of mental ill health and worse occupational outcomes for BAME staff. This study aims to identify ethnic inequalities in mental health and occupational outcomes amongst NHS staff how COVID-19 exacerbates such inequalities, and the processes which inequalities are produced, maintained and resisted. We also aim to develop a Race Equality Assessment toolkit, as well as education and training resources targeted at improving BAME staff experiences, retention and relevant NHS policies. To address these aims we will involve service users and BAME staff representatives in deciding the content of the survey and interviews, co-leading interviews and in developing the toolkit; collect new quantitative (survey) and qualitative (interview) data on BAME staff experiences since COVID-19; develop the toolkit to help ensure BAME perspectives are prioritized in research and education for all NHS staff; and develop education and training resources targeted at improving BAME staff workplace experiences, job retention and reducing inequalities faced by BAME staff during and beyond COVID19. To do this, we will incorporate an ethnicity module into an ongoing national longitudinal study of NHS staff (NHS CHECK) to assess health and work outcomes by ethnicity over an 18-month period. With the additional ethnicity module, the NHS CHECK cohort will uniquely capture existing and emerging ethnic inequalities in mental health and occupational outcomes during and after COVID-19. We will also carry out interviews with BAME staff who take part in the NHS CHECK study; London based healthcare practitioners from difference ethnic backgrounds who have previously been interviewed before COVID-19 as part of the Tackling Inequalities and Discrimination Experiences in health services (TIDES) study; and NHS managers and senior staff nationally from BAME and non BAME groups. Data will inform NHS Trusts, NHS England and the public through current initiatives tasked with making sustainable transformations for BAME staff within the workplace )e.g., NHS England Workforce Race Equality Standard) and communities (e.g., Black Thrive). Findings will be used to develop education and training materials to support BAME NHS staff nationally through collaboration with psychologists, medical educations and equality and diversity professionals. These will also be subsequently piloted prior to scale up through our collaborators, such as NHS England Workforce Race Equity Sta",2020,-99,King's College London,619969.97,Human Populations,Asian | Black,Unspecified,Unspecified,Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce, +C01177,ES/V009370/1,Gendering the UK's social policy response to the COVID-19 crisis,"The COVID-19 outbreak and resultant economic crisis have led to governments around the world, including the UK, taking extraordinary action to support citizens, many of whom are facing unprecedented shocks to their livelihoods. For example, the UK has launched the Job Retention Scheme (JRS), the Self-Employment Income Support Scheme (SEISS), and changes to benefits. The JRS pays workers who are not needed during the pandemic at 80% of their earnings up to £2500 per month, while the SEISS pays a taxable grant of 80% of average annual earnings for the previous three years to self-employed people earning less than £50,000 per year. The Government has also increased the support provided by existing benefits such as Universal Credit and Working Tax Credit. Bodies such as the International Labour Organisation (ILO) recommend that government support should target those most affected by the economic fallout from COVID-19. Women form one of these groups - research has already shown that women in the UK are more likely than men to have become unemployed or to have reduced earnings, largely as a result of over-representation in precarious, low-paid work and shut-down economic sectors. School and nursery closures have intensified women's disproportionate responsibility for unpaid care work, and gender intersects with wider structural inequalities which place particular women - including single mothers and BAME women - at greater risk of negative economic consequences. To mitigate these impacts and ensure a gender-sensitive recovery from the crisis, there is an urgent need for gendered perspectives to be built into emergency and long-term social policy responses. However, there is currently a lack of knowledge on how this can successfully be done. To fill this gap in knowledge, our project explores whether the current UK social policy response is gender-sensitive in design, access, and impacts. We do this by (1) documenting and comparing social policy responses around the world to investigate whether the response in the UK is more or less gender-sensitive than that of other countries (2) assessing the reach of UK government social support to different groups through a gendered analysis of uptake and (3) exploring the impact of different policy approaches on longer-term indicators of gender inequalities through and after the crisis. The project will highlight the policy options that are most likely to mitigate gendered economic and social risks in the short and longer term and promote the most gender-equitable recovery from the crisis.",2020,-99,King's College London,84963.62,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts, +C01178,ES/V010018/1,Social learning about COVID-19 vulnerability and social distancing in high density populations: the case of UK urban dwelling Bangladeshis,"Early epidemiology indicates older members of Britain's Bangladeshi communities are disproportionately affected by COVID-19 related morbidity and mortality. Bangladeshis are more likely to have comorbidities and live in poorer, overcrowded areas in the UK's urban centres where viral contagion is more likely. This cross-section of socioeconomic, geographical and health related factors underlines the need for clear messaging about social distancing in a complex and shifting risk scenario - messages that this vulnerable group, who speak an oral language (Sylheti), may not be able to access directly due to low literacy and English language proficiency. This study will identify the practices adopted by Bangladeshis in a London borough in response to the pandemic, the attitudes and beliefs that underlie them and whether and how these have been influenced by messages about social distancing. Drawing on our earlier work, it will examine the role of social learning in how messages are accessed and interpreted and whether and how the health interactions of this older group are mediated by friends, family members and acquaintances. Remote interviews with older Bangladeshis and their social contacts who perform this mediating role will provide insights into how linguistically and culturally appropriate messaging can build on existing beliefs and practices to promote compliance, and on social mediation as a dissemination strategy. We will identify the role of choice of language (English or Sylheti), the differences between written and oral representations of COVID-19 risk, and the manifold ways in which linguistic choices give salience to aspects of a risk scenario.",2020,-99,King's College London,166083.04,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C01179,ES/V009451/1,Pandemic Policing: public attitudes towards compliance and organisational resilience,"The UK's COVID-19 response has provided the police with new powers which potentially impinge upon civil liberties, altering the nature of policing activities. National policing bodies have encouraged a compliance not coercion approach based upon the 4 E's of Engage, Explain, Encourage and Enforce. In an innovative collaboration between the University of Portsmouth and Hampshire Constabulary, this research considers the impact of pandemic policing on the police and the public. It seeks to analyse the experiences of police officers and police leaders in exceptional circumstances and to explore the physical and psychological challenges of pandemic policing. This knowledge will provide evidence of i) organisational resilience, risk identification and effective decision-making, ii) strategies for the maintenance of future service delivery and iii) the impact of pandemic policing on police wellbeing. The research will also consider how the worldviews of individuals influence their perceptions of COVID-19 restrictions, their willingness to comply and key drivers of compliance/non-compliance which will shape the medium-long term police response. This knowledge will provide evidence of iv) effective policing in a crisis, v) public satisfaction/confidence in the police, vi) whether and for how long the public are willing to suspend their civil liberties and vii) factors that underlie any social/spatial variability. The link between perceptions of police legitimacy and willingness to comply means this understanding is crucial. Research findings will be scaled up into evidenced-based policing policies/practices nationally and its impact assessed and practices modified over the period of the crisis and beyond.",2020,-99,University of Portsmouth,207468.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Policy research and interventions | Indirect health impacts, +C01180,ES/V009907/1,COVID-19: Resilience of the UK seafood system to the Covid-19 disruption (RiseUp),"The UK seafood industry is under unprecedented pressure to deliver on national food security during COVID-19/SARS-CoV-2 pandemic, while trying to adapt to remain socio-economically viable. However, no data exists on the systemic impacts to the UK seafood industry, adaptation actions employed by businesses and their potential effects on seafood supply. This compromises the timely adoption of measures to address challenges currently faced by businesses and delays the implementation of changes to increase the UK seafood industry's resilience to future shocks. RiseUP brings together the expertise of SAMS, the University of Manchester and Seafish to explore pathways to increase resilience at the system and business levels and provide policy-relevant recommendations and stakeholder-specific advice to address challenges. It will collect evidence on the impacts of COVID-19 disruption across the UK seafood industry, how these are managed by businesses and how impacts are propagating trough the supply network. A mix-method approach combines data collection through interviews and surveys; modelling of the industry supply network to explore systemic, particularly unintended, consequences to its resilience; and in-depth case studies to investigate business model adaptation and circularity in selected sectors. The project will provide evidence for decision-making under pressure and uncertainty, to manage the COVID-19 disruption. The project will outline areas for immediate action and inform strategic changes to increase the resilience of the UK seafood industry to future shocks. RiseUP will contribute to understanding the routes to increased resilience, sustainability and security of the UK's seafood system.",2020,-99,Scottish Association for Marine Science,389469.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01181,ES/V009788/1,Will COVID19 Change What The Public Expect of Government?,"COVID19 has created a major social and economic shock that has impelled government intervention on a scale unprecedented in peace time. A key question that now arises is whether this experience has changed voters' expectations of what government can and should do - and so altered the climate of public opinion with which politicians will have to deal once the public health crisis has ended. This study will use survey research to assess whether attitudes in Britain have changed in three areas. First, has the anxiety created by the crisis and the experience of social distancing made us more or less trusting of others and tolerant of those who behave differently from ourselves? Second, has the economic shock and risk of unemployment changed our attitudes towards government spending and the provision of welfare to those of working age? Third, has the experience of an internationally transmitted disease created an increased wish to control our borders, most notably in respect of immigration? The first survey will be conducted in 2020, the second in 2021. Both will ask questions that were previously asked on surveys before the pandemic, thereby making it possible to see how attitudes have changed.",2020,-99,NatCen Social Research,379198.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts, +C01182,NERCCOVID004,Air quality and environmental impacts of Covid-19,Air quality impacts resulting from changes in behaviour in response to Covid-19.,2020,-99,National Centre for Earth Observation,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01183,NERCCOVID005,Improved understanding and prediction of the Covid-19 pandemic using data assimilation with epidemiological models,"Study aiming to re-engineer data assimilation for the epidemiological context, thus improving how models are informed by data and their predictions whilst simultaneously focusing on questions which will help to guide current and future strategies in dealing with pandemics.",2020,-99,National Centre for Earth Observation,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,, +C01184,NERCCOVID006,Covid-19: Air quality,"Data collection for national air quality networks, particularly the live networks which provide pollution data hourly. To support the ongoing evaluation of risk during the COVID-19 outbreak due to the potential impact of air pollution on respiratory illnesses.",2020,-99,UK Centre for Ecology & Hydrology,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01185,NERCCOVID007,Covid-19: review of impacts on mineral and metal raw materials,Review of the current and likely COVID-19 impacts on UK security of supply of mineral and metal raw materials.,2020,-99,British Geological Survey,,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01186,NERCCOVID008,Revised methodology for geological and hydrological reports for agencies in support of their Covid-19 emergency duties,Revised methodology to deliver a rapid turnaround for detailed geological and hydrological information for the expansion of existing or the development of new cemeteries,2020,-99,British Geological Survey,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01188,NE/V009400/1,The Hidden Rise in Toxic Air Pollution during the COVID-19 Pandemic: is our response worsening the respiratory burden of particulate matter in the UK?,"Recent research has highlighted the concerning paradigm that reducing ambient concentrations of legislated air pollution, in the form of PM2.5, may lead to a decline in air quality by increasing the concentration of more harmful ultrafine particles (UFP; diameter less than 100nm). It has been shown that PM2.5 plays a crucial role in suppression of UFP numbers, with larger PM2.5 particles acting to scavenge the more toxic UFP from the air. Consequently, removal of PM2.5 as a UFP sink may result in enhanced ambient UFP numbers, particularly if UFP emissions and gaseous precursor concentrations remain unchecked. With the outbreak of the COVID-19 pandemic, anthropogenic activity around the globe has decreased in a vast and unprecedented manner, to such an extent that concentrations of commonly measured primary air pollutants have decreased dramatically. However, levels of secondary pollutants (which often correlate with finest UFP fractions) have already begun to rise. It follows that this sudden, global drop in anthropogenic activity and ambient PM2.5 has the potential to drive an unexpected and potentially significant increase in UFP concentrations and associated detrimental health effects. If we are now inadvertently adding an unlooked-for cardio-respiratory pollutant into the air at a time when many are vulnerable to a virus that impacts the respiratory system, we risk widening the COVID-19 'window of vulnerability', where increased UFP exposure acts to exacerbate underlying conditions for individuals with pre-existing co-morbidities, who may otherwise be considered 'lower risk', and worsen the impact of the virus for those already considered as 'at risk'.",2020,-99,University of Brighton,64780.69,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01189,NE/V00946X/1,"COVID 19 - Reduced Air Traffic due to Coronavirus, Environmental Impacts","The aviation industry is responsible for at least 5% human climate impact, despite producing only 2.5% of CO2 emissions. A key driver of this is contrails, which have a particularly large effect by trapping heat in the troposphere. However, their impact is poorly understood due to difficulties in studying contrails, especially for situations where contrails spread out into large, long-lived, cirrus clouds. The unprecedented reduction in aviation due to the pandemic allows us to isolate and track individual contrails using satellite data, which is usually very challenging. The relatively clear skies during the pandemic also enable us to much better estimate the impact of aviation by comparing airspace and contrail formation during the shutdown against normal conditions. Furthermore, as the pandemic subsides there is a unique and urgent opportunity for the UK government to support aviation in an economically and environmentally friendly manner - especially in the context of controversial decisions such as Heathrow's third runway. This project will use unique data sources to conduct cutting-edge research into aviation's environmental impact, contrails in particular, to allow the government to make evidence-based decisions on financial and regulatory support to the industry as it returns to flight operations in the future.",2020,-99,University of Oxford,86763.62,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01190,NE/V00963X/1,COVID-19: Rapid detection of the impact of COVID-19 on UK greenhouse gas emissions,"The nationwide restrictions on social interaction brought about by the COVID-19 outbreak have the potential to dramatically change the UK's greenhouse gas (GHG) emissions. However, given the lack of precedent, it is difficult to predict the sign, magnitude, or spatial and temporal change that may occur. Atmospheric GHG observations are sensitive to emissions changes over very short timescales (hours to days), and therefore ""top-down"" (atmospheric data-based) inference of GHG emissions has the potential to provide rapid updates to climate researchers, the public and stakeholders (e.g. BEIS and the UK's GHG inventory compilers). There have already been reports of reductions in atmospheric concentrations of GHGs and air pollutants in the media from across the world. However, these reports have sometimes lacked scientific rigour, ignoring the critical influence of meteorology and seasonality. Here, we aim to use data from the UK's unique GHG measurement network (the UK DECC network) and adapt our atmospheric modelling and statistical inference frameworks to provide robust information on any rapid changes in UK GHG emissions that occur during the period of COVID-19-related restrictions. Conversely, the change in anthropogenic activity provides an unprecedented opportunity to test top-down (atmospheric data-based) emissions inference frameworks, such as those used to report UK GHG emissions to the United Nations Framework Convention on Climate Change (UNFCCC).",2020,-99,University of Bristol,98000.49,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01191,NE/V009656/1,Does nature-based citizen science enhance well-being and mitigate negative effects of social isolation?,"There is concern about the negative impacts of COVID-19 movement restrictions and social distancing on people's wellbeing and mental health. Engaging with nature is known to positively impact upon people's wellbeing and this has been promoted by many organisations. Evidence of the benefits of nature-based activities on wellbeing has come from 'noticing nature' activities where people pause and enjoy nature, sometimes with a creative response (e.g. writing or drawing). Nature-based citizen science is another way of connecting with nature and has the added value of collaboration and having a specific purpose, but its benefits have not so far been evaluated. We will undertake a large-scale randomised trial of the impact of citizen science and/or 'noticing nature' activities on people's nature connectedness and wellbeing, promoted through broadcast, print and social media. The outcome will be evidence-based recommendations on the use and design of nature-based citizen science to mitigate the negative effects of social isolation during the COVID-19 crisis and beyond.",2020,-99,UK Centre for Ecology and Hydrology,56948.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01192,NE/S016287/1,Covid-19 Digital Sprint. CINITDIEN - Championing INnovation In the DIgital Environment,"The overall purpose of the Digital Sprint is to elicit from the research and innovation community novel ideas and contributions to provide environmental solutions to the COVID-19 pandemic. The Digital Sprint will be an interconnected series of activities encompassing an initial concept-gathering Ideathon event, followed by a Kaggle challenge and three targeted Hackathon events. It seeks to leverage the use of cutting-edge technology to support environmental solutions through key NERC digital assets and datasets as well as datasets from health, social science and other disciplines, and policy partners. It will draw across the capabilities available to NERC in the Digital Environment Expert Network and the broader NERC and other relevant research and user communities. The activities will develop bridges to comparable programmes, such as the Alan Turing Institute DECOVID1 programme and the Kaggle community COVID-19 challenges. These activities will support several of the ambitions in the NERC Delivery Plan, in particular the key role in the provision of environmental solutions in supporting cross-sector collaboration to tackle key challenges.",2020,-99,Cranfield University,48368.34,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,, +C01193,NE/V009710/1,Improving COVID-19 forecasts by accounting for seasonality and environmental responses,"Policy-makers urgently need medium- and long-term forecasts for SARS-CoV-2, but we are currently ignorant of the virus' seasonal dynamics. In the absence of data, forecasters have been forced to assume that SARS-CoV-2 will have identically strong environmental and seasonal responses to other coronaviruses[1]. We will address this important source of uncertainty by measuring changes in transmission across climatic gradients (e.g., temperature and humidity) to forecast seasonal responses. We will do so by leveraging classical ecological theory related to niche modelling (the measurement of species' environmental tolerances) and space-for-time substitution (using variation across space to predict variation through time). We will integrate this approach into existing forecasting models developed by the Imperial College London COVID-19 Response Team, which have informed the public-health response worldwide. This will allow mitigation strategy to account for climate-driven spatial changes in transmission, highlighting where and when stronger interventions are needed. As SARS-CoV-2 is evolving, and so potentially adapting, as it spreads, we will also conduct preliminary work to assess the extent to which the virus is adapting in situ to environmental conditions. This project will provide new insight into the relationships between SARS-CoV-2 transmission rates, seasonality, and environmental factors, which will inform the development of targeted optimal intervention strategies against COVID-19. We have prioritised our efforts around delivering forecasts before autumn and winter, leveraging an inter-disciplinary team of epidemiologists, quantitative ecologists, evolutionary biologists, and bioinformaticians. [1] Kissler et al. (2020) Science eabb5793.",2020,-99,Imperial College London,348524.44,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics, +C01194,NE/V009737/1,COVID-19: Probing Air Quality Controls in the Oxford-Milton-Keynes-Cambridge Arc,"UK cities regularly exceed air quality (AQ) compliance limits. On-going improvements in AQ will be offset by planned growth in some regions. More detailed observations during a period of quickly changing pollutant emissions would expand our understanding of the complex interactions between human activities, pollutant emissions and AQ control measures. A focus will be the differing responses of particulate matter (PM) and gaseous pollutants. The COVID-19 period provides an unprecedented opportunity for additional measurement to illuminate factors which influencing UK air quality and health. Cranfield University (CU) is a controlled mixed (urban and rural) site in the ARCs heart. It has a self- contained campus with a unique combination of infrastructure, site types and facilities. The Cranfield Urban Observatory reference station is operating, and multi-species sensor units are available for immediate use. In this project, these units would be deployed as soon as possible at identified sites across the Oxford-Milton Keynes-Cambridge Arc (ARC) in order to provide a detailed observational record during a period of low traffic and industrial activity while COVID-19 restrictions are in place and being eased. Real-time information can be provided on the interaction between air quality and the easing of social distancing measures. These measurements made during a period of known intervention measures will inform infrastructure planning for the ARC and the design of Low Emission Zones and air quality policy more generally. The data will be available for use by researchers looking at before/during/after effects of these measures.",2020,-99,Cranfield University,178184.94,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01195,NE/V010360/1,Assessing environmental impacts of COVID-19 emergency public health measures in Oxford City.,"Emergency public health measures were implemented across the UK in early 2020 to suppress COVID-19 transmission; with major implications for ambient air quality (AQ). Well publicised satellite data have indicated associated reductions in air pollutant (AP) concentrations with potential benefits for human health; however ground-based measurements suggest more complex trends in UK cities. These events present a unique natural experimental opportunity to better understand environmental consequences arising from these measures and to apply this learning to future AQ intervention scenarios. Our research focus is Oxford (population ~155,000). Oxford has significant AQ and health inequity challenges, with the equivalent of 1 in 20 early deaths attributed to AP exposure. The City and County Councils plan to introduce a Zero Emissions Zone and enhanced Low Emission Zone from 2021 and to achieve carbon neutral status by 2030. Oxford is also a focal point for existing research activity, including NIHR, Defra, Highways England and Research England funded studies supporting a broad range of environmental and transport monitoring capabilities and existing research infrastructure, which we plan to utilise and repurpose for this study. We plan a 18 month study to integrate longitudinal data arising from multiple observational inputs (e.g. AQ, noise, smart roadside sensors) to enable robust evaluation of the positive and negative impacts of introduction, maintenance and removal of COVID-19 measures in Oxford City. The data we assimilate will be used to generate a series of AQ control scenarios and predicted health benefits, thereby informing and redefining council-led AQ policy and climate strategy.",2020,-99,University of Birmingham,254516.61,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01196,BB/M02542X/1,Three species viral zoonotic infections - a systems virology analysis,"Recent high profile events highlight the transmission of bat viruses to humans, usually involving an intermediate farmed/companion animal host. These include Hendra (bats - horses - humans), Nipah (bats - pigs - humans), SARS-CoV (bats - palm civet - humans) and MERS-CoV (bats - camels - humans). Thus, there is an established paradigm of new viruses passing from wild animals to farmed/companion animals and/or humans. There is every possibility that this kind of jump from bats to humans via another animal - which is known as a zoonosis - could keep happening in the future. Bats make up almost 20% of all living mammals and they are found almost everywhere on the planet, which means that new viruses spreading from bats to animals and humans could happen anywhere. Bats are widespread and carry a range of viruses similar to MERS-CoV/SARS-CoV and in the UK, bats come into contact with a range of wild and farmed animals. Thus, a new outbreak is as likely to happen here as anywhere else. In addition to the threat to human health, this kind of three-stage zoonosis poses two potential food security issues; one is that the novel virus impacts animal health directly (e.g. effects ranging from a failure to gain weight to mortality). The second is an indirect impact on food security resulting from the threat to human health, e.g. Nipah virus outbreaks have resulted in the wholesale slaughter of farmed pigs. A key barrier to understanding how serious a disease might become, or which animals might be affected in zoonotic events, is that we have little information on how the emerging virus interacts with the regulation of transcriptional and translational systems in different animals. This means we do not understand how the virus might interact with a new host species, which will influence whether the virus successfully replicates and whether the infection will cause disease or fatalities. In human virus research, techniques such as high-throughput proteomics/transcriptomics/interactomics have been successfully used to reveal how viruses modulate and interact with thousands of human genes and proteins. This new ""systems virology"" approach even suggests ways of combating or managing the disease. Studying a zoonotic virus with a potential to impact food security, in the same level of detail, could help us understand the pronounced differences in pathogenicity of these viruses in different animal and vector species. Crucially, this will reveal how viruses adapt and jump into other animals, or if certain species jumps are more likely than others. In turn, this will help inform policy by allowing predictions of which animals may readily act as new hosts, or are likely to suffer severe pathogenic responses, and thus can be controlled accordingly. The ability to do this type of research in non-human species (i.e. the animal reservoirs and intermediate hosts of zoonotic infections) has a number of serious bottlenecks. This is because the ""systems virology"" approach requires high-throughput methods of detecting and identifying gene transcripts and proteins, which is still a major challenge in non-human species. Even if there is a genome sequence available, it will not have been annotated with regard to i) the identification of orthologous genes, ii) the full complement of gene transcripts, for example, differentially spliced transcripts, and iii) the proteins encoded by these transcripts. We have developed a world-leading technique (called PIT analysis) that allows us to use high-throughput techniques to study virus-host interactions in any animal with the same precision as we can currently apply to human diseases. In this project we will examine how a zoonotic virus interacts with three different animals (including humans), identifying the different cellular pathways that are affected and help us understand how viruses jump from one animal to another",2020,2020,University of Bristol,602333.07,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2016 +C01197,BB/N002350/1,Understanding the function and formation of infectious bronchitis virus membrane rearrangements,"Poultry products are a major source of animal protein for human consumption with approximately 55 billion chickens raised globally every year. The UK poultry industry contributes approximately £3.4 billion to the economy annually but infectious diseases, including viruses, are a continual threat to animal welfare and productivity. The infectious disease that results in the largest economic losses to the UK poultry industry is caused by infectious bronchitis virus (IBV). IBV infection results in animal welfare costs and significant economic losses due to poor meat quality, poor egg production and poor egg quality. It is estimated that IBV affects 22 million chickens and costs the UK poultry industry £23 million every year. Currently available vaccines against IBV are costly to produce and do not protect against all of the different circulating viral strains. Therefore, new vaccination strategies are required. By understanding how IBV replicates itself and how it manipulates the host cell to allow replication, it will be possible to develop alternative and potentially more efficient control strategies, benefitting animal welfare, the poultry industry and the UK economy. IBV is a coronavirus with a positive strand RNA (+RNA) genome. A critical step during the life cycle of coronaviruses is RNA synthesis, the process of copying the viral genome for packaging into new virus particles and to allow viral proteins to be produced. IBV RNA synthesis, as for all +RNA viruses, is closely linked with the rearrangement of cellular membranes, providing a platform for the assembly of the viral proteins responsible for RNA synthesis, known as replication-transcription complexes (RTCs), and protecting viral RNA from host defences. However, IBV induces more than one type of rearranged membrane and the role of these different structures in the virus life cycle is not known. This proposal aims to understand the formation of IBV RTCs responsible for viral RNA synthesis. Specifically we will identify where in the cell viral RTCs are located and RNA synthesis takes place. We will also identify which viral and cellular proteins are important for the formation of rearranged membranes. The information gained will not only be useful for understanding how IBV and other coronaviruses replicate but will provide insight into potential ways to alter or prevent virus replication for future vaccine and anti-viral development.",2020,2020,The Pirbright Institute,553480.07,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2016 +C01202,BB/V003976/1,Untargeted metabolomics of serum samples during COVID-19 disease progression,"Understanding changes in the biochemistry of an individual who is ostensibly healthy, including when they may show no overt symptoms of infection with SARS-Cov2, remains a huge challenge. Similar questions apply to understanding who is likely to live (unaided or via intervention) and who will die from COVID-19 once diagnosed, and the answers are equally unknown. Since we do not presently have any knowledge (although we know that there are cardiovascular changes that should have easily measured metabolic consequences (Zheng YY, Ma YT, Zhang JY, Xie X: COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020), the best approach is to measure everything and find out. This approach is known as 'untargeted metabolomics'. We are experts in it (Kell co-invented the term 'metabolome'), and have already discovered novel measures of cardiovascular stress. We now wish to apply these to cohorts of serum samples that are already being collected in Liverpool and which will be made available to us (after treatment to remove all proteins, including virus). We anticipate that we shall be able to find markers that could be very early predictors of COVID-19 infection and prognosis.",2020,-99,University of Liverpool,209939.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C01203,BB/V004174/1,The Virus Analysis Tool (VAT) - A computational tool for the characterisation and monitoring of viruses during an acute outbreak,"A main limitation of the response to novel virus outbreaks is the lack of information. While virus identification by next generation sequencing is quick, the investigation of the clinical and biological virus properties takes much longer. Moreover, methods for the early detection of novel virus strains with changed pathogenicity, transmissibility, drug sensitivity, and/ or immunogenicity are needed. Computational approaches have the potential to fill these gaps. We have created a method that identifies determinants of virus behaviour by identifying amino acid sequence positions that are differently conserved between related viruses and subsequent computational modelling of their impact on protein structure/ function. Our research has already identified substantial differences between SARS-CoV-2 and SARS-CoV. Although SARS-CoV-2 and SARS-CoV share a sequence identity of about 80%, the majority of the remaining positions are differentially conserved, which is reflected in differences in clinical behaviour, cell tropism, and drug sensitivity. Here, we will develop this approach into a webserver (the 'Virus Analysis Tool', VAT) that can be used by everyone involved in SARS-CoV-2 research and treatment. In the current outbreak, VAT will enable researchers to compare the genomic sequences of novel SARS-CoV-2 isolates to those of other SARS-CoV-2 strains and to identify novel strains rapidly, which are likely to be characterised by changes in phenotype, for example in disease severity, drug sensitivity, or immunogenicity. Hence, VAT will be a tool for the effective monitoring of the emergence of novel virus variants. VAT will also increase our preparedness for future virus outbreaks.",2020,-99,University of Kent,68208.93,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01204,MC_PC_20001,Enhancing National Covid-19 Screening and Diagnostic Support Capacity in Uganda,This £40k award award is to procure an Applied Biosystems Real Time PCR machine to support the Centres important work on COVID-19. This exceptional award is being made in recognition of the fact that research will be critical in overcoming this epidemic.,2020,2021,London School of Hygiene & Tropical Medicine,49080,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Uganda,,,2020 +C01205,MC_PC_20002,SARS-Cov2 equipment purchases for HIU to support their COVID-19 activities,This £246k award is to procure equipment to support the Units important work on COVID-19.This exceptional is being made in recognition of the fact that research will be critical to overcoming this epidemic.,2020,2021,University of Oxford,301842,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2020 +C01206,MR/R015600/1,MRC Centre for Global Infectious Disease Analysis,"The continued threat posed by emerging infectious diseases has been highlighted in recent years by the emergence of MERS-coronavirus in the Middle East, Ebola in West Africa and Zika in Latin America. Preparedness therefore remains a policy priority for public health agencies and governments worldwide. In addition, as new vaccines, drugs and other interventions are developed for endemic diseases such as malaria, HIV and TB, there is a need to extrapolate from clinical trial results to determine which combination of interventions gives the optimal (or most cost-effective) control strategy for a specific disease in a particular setting. In this context, modern epidemiological modelling and analysis methods have proven themselves increasingly powerful tools for giving insight into the patterns of emergence of novel outbreaks, the transmission dynamics of endemic diseases and the options available for the control of both. The Centre for Global Infectious Disease Analysis is a world leader in research in this area, and in translating our research into improved public-health decision-making. Since it was founded, MRC funding has supported this translation by facilitating the forging of close partnerships with all major global health organisations (e.g. WHO, PHE, CDC, BMGF, The Global Fund, Gavi) and research centres and public health agencies in many low and middle income countries (LMICs). Continued funding for the Centre will allow existing partnerships to be sustained and enhanced, and new collaborations with researchers and health agencies in LMICs to be developed. By supporting PhD training and postdoctoral career development, it will also continue to expand the UK skill base in mathematical modelling and advanced analysis applied to health problems. Last, continued MRC support will pump-prime new priority research areas, including work on improving the development of new vaccines and on tackling the global challenge posed by antimicrobial resistance.",2020,2023,Imperial College London,5529071.82,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2018 +C01207,MR/T027355/1,Ecology or genetics? Adapting machine learning approaches to understand determinants of cross-species transmission and virulence in RNA viruses,"Emerging infectious diseases remain a prominent threat to global health, e.g., Ebola virus, Zika virus. In 2015, the WHO designated 'Disease X' to indicate the serious potential of previously unknown emerging pathogens to cause public health crises. Though zoonotic RNA viruses are known to present higher risks of emergence, detailed determinants of cross-species transmission remain unclear. Zoonotic viruses also vary widely in their capability to cause severe disease. To predict public health impacts of 'Disease X', a better understanding of which traits drive this variation in infectivity and virulence is urgently needed. Whilst previous approaches have focused on ecological predictors, these traditional frameworks have been unable to capture the information within increasingly available RNA virus sequences. This research aims to capitalise upon the potential power within large genetic data resources and quantify comparative influences of genetic versus ecological traits of RNA viruses and hosts upon cross-species transmission dynamics. To fully integrate novel, high-dimensional genetic data, new analytical approaches are needed. I will apply machine learning as a state-of-the-art statistical methodology, comparing several advanced approaches, e.g. gradient boosting, a method of gradual model learning which outperforms traditional methods. Models will span all known mammal and avian RNA viruses (22 families) using the exceptional breadth of EID2, a large, host-virus infectivity dataset. This project will additionally develop further text-mining tools to capture and integrate virulence data within EID2. The proposed models will allow tests of evolutionary theory across a range of RNA viruses. Quantified model outputs will contribute to public health risk assessments by informing prioritisation for novel viruses and advancing frameworks for emergence predictions, moving towards a 'smarter', empirically-driven strategy to prevent future disease burden.",2020,2022,University of Liverpool,289151.14,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2019 +C01208,MC_UU_12014/10,Innate Immunity and Host Species Barriers,"In vertebrates, the interferon (IFN) response is the first line of defence against viruses, stimulating the production of diverse antiviral proteins encoded by hundreds of IFN-stimulated genes (ISGs). These host defences are engaged in continuous evolutionary conflicts with viruses, which have evolved a variety of evasive counterstrategies. Most viruses are only able to efficiently infect and replicate within a limited set of species, and multiple lines of evidence indicate that the IFN response plays a key role in limiting cross-species transmission. Sometimes, however, viruses do succeed in ""jumping"" from one species to another - indicating that host innate defences have been overcome. Since most emerging viruses (e.g. Ebola virus, coronaviruses, Nipah virus etc.) persist in animal reservoirs, it is vital to understand the barriers that normally prevent cross-species transmission. In this programme, we will first characterise the ISGs of a variety of animal species, including reservoirs of zoonotic infections. We will then examine a range of important human pathogens (e.g. Ebola virus, hepatitis C, Dengue and others) in vitro and in silico to (i) define patterns of antiviral restriction by ""homologous"" and ""heterologous"" ISGs and (ii) identify important host and viral determinants of cross-species transmission. We will develop experimental systems that will allow us to dissect the evolutionary history of antiviral genes, and explore the pathways and constraints to the evolution of viral counterstrategies. Altogether, these data will provide a powerful and flexible system for (i) constructing predictive models (a ""zoonotic index"") to assess the risk of future cross-species transmission events and (ii) identifying novel antiviral genes.",2020,2021,University of Glasgow,3625785,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Animal source and routes of transmission,2016 +C01209,MC_UU_12014/9,Respiratory infections,"Multiple viruses are responsible for respiratory infections and co-infections causing a variety of disease outcomes that range from a mild cold to life-threatening viral pneumonia. Occasionally, respiratory viruses result in emerging infections such as the swine-origin influenza A virus (that caused the 2009 pandemic) or the severe acute respiratory syndrome coronavirus that caused an extended outbreak in several countries in early 2000s. Molecular diagnostic assays are routinely used in the UK healthcare system and they can simultaneously test for the presence of multiple viruses. Databases with results from such diagnostic tests represent a rich source of information that can reveal insight into the epidemiology of viral respiratory infections in the patient population. Respiratory viruses are generally studied as single entities and not as a community. Since they are obligate intracellular pathogens that infect a well-defined ecological niche (the human respiratory tract), studying them as a community is a logical approach to capture the impact of their complex interactions on their infection dynamics. We propose to study the infection dynamics of a group of respiratory viruses in a large and well-defined population over an extended period of time. We will analyse the long-term trends in viral respiratory infections using information on diagnostic test results (and associated metadata) of the Greater Glasgow and Clyde Health Board (GGCHB, the largest Health Board in Scotland) patient population. We will sequence a large number of viruses from clinical specimens to determine their complete genomes, study their evolutionary dynamics and to identify mutations that might be associated with changes in their phenotype (virulence, seasonality, age group distribution, etc.). We will use mathematical and statistical models to infer interactions among viruses at the patient level and their impact at the epidemiological scale. Finally, we will develop bioinformatics tools to facilitate the future use of complex sequence data in diagnostic laboratories and public health bodies.",2020,2021,University of Glasgow,1761972,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2016 +C01210,C19-IUC-001,Modelling the epidemic curve,"Statistical analyses of COVID-19 data on death and hospitalisation, and modelling of the epidemic curve in the UK using data provided from PHE",2020,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Prognostic factors for disease severity, +C01213,C19-IUC-005,Participation in coordinating the RECOVERY Trial,RECOVERY Trial - repurposing existing and new drugs for COVID-19 patients.,2020,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C01214,C19-IUC-198,Evaluation of a new rapid COVID-19 diagnostic test,"A University of Cambridge spinout company, Diagnostics for the Real World, has developed a rapid and accurate point-of-care system (SAMBA II) for the diagnosis of infection with SARS-CoV-2. The COVIDx clinical study is now underway to evaluate the SAMBA II machines, which are able to deliver a diagnosis in less than 90 minutes.",2021,-99,MRC Cancer Unit at the University of Cambridge,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C01215,C19-IUC-225,Evaluation of Cytosponge testing for urgent suspected cancer referrals during COVID-19 related suspension of endoscopy services,Upper GI endoscopy services are severely limited in view of the risks of aerosol spread of coronavirus. This risks a delay in cancer diagnosis and a back-log of endoscopy referrals to facilitate once services resume. We have fast-tracked the Cytosponge technology developed in Cambridge to provide a triage service for 2WW referrals.,2020,-99,MRC Cancer Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01216,C19-IUC-018,"Genetic determinants of COVID-19 susceptibility, severity and outcomes","Project investigating the genetic determinants of COVID-19 susceptibility, severity and outcomes, in collaboration with The COVID-19 Host Genetics Initiative",2020,-99,MRC Centre for Drug Safety Science at the University of Liverpool,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C01217,C19-IUC-019,Benefit versus risk for anti-SARS-CoV-2 agents,Investigating the likely effects of anti-SARS-CoV-2 agents at different parts of the viral life-cycle,2020,-99,MRC Centre for Drug Safety Science at the University of Liverpool,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01218,C19-IUC-021,A cell-based reporter assay screening compounds for anti-SARS-CoV-2 activity,Development of a cell-based reporter assay to generate a medium-throughput assay for screening compounds for anti-SARS-CoV-2 activity,2020,-99,MRC Centre for Drug Safety Science at the University of Liverpool,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01219,C19-IUC-212,Evaluating the safety of angiotensin pathway drugs in COVID-19.,Safety of angiotensin pathway drugs in COVID-19,2020,-99,MRC Centre for Drug Safety Science at the University of Liverpool,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",, +C01220,C19-IUC-184,Aerosol measurements in ICU,High time resolution aerosol size distribution measurements in an intensive care unit (ICU) including assessing aerosol generation from patients under different ventilation methods and procedures. The study also involves personal exposure of front-line staff.,2020,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings, +C01222,C19-IUC-194,What is the impact of the Covid-19 pandemic on non-Covid-19 morbidity and mortality?,Study to evaluate the impact of the COVID-19 pandemic on non-COVID-19 morbidity and mortality including impacts of health inequalities. Findings will inform health policy and resource allocation decisions at local and national level,2020,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01223,C19-IUC-195,The availability and accessibility urban parks and gardens during social distancing measures,Study of the availability and accessibility of urban parks and gardens during social distancing measures,2020,-99,"Imperial College London, King's College London",,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C01224,C19-IUC-223,REal-time Assessment of Community Transmission (REACT),"REACT-1: Study of SARS-CoV-2 antigen prevalence in England among 100,000 randomly selected people from age 5 years. REACT-2: Feasibility and usability of lateral flow tests to assess SARS-CoV-2 antibody levels in the general population.",2020,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C01225,C19-IUC-133,Brain development and intra-uterine SARS-CoV-2 virus exposure,"To study the effect of viral infection on foetal brain development using magnetic resonance imaging (MRI), comparing seropositive SARS-CoV-2 with seronegative SARS-CoV-2 mothers.",2020,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C01226,C19-IUC-134,Biomathematical methodology to obtain accurate COVID-19 pandemic estimates from incomplete data,"To assess the asymptomatic infection rate using Italian and world-wide data as part of a collaboration with ISPI (Bocconi University, Italy). To use these estimates to inform policy and inform simulations of end-of-lockdown scenarios",2020,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,Italy,Epidemiological studies,Disease transmission dynamics, +C01227,C19-IUC-158,Resilience in Education and Development (RED) Study,"To explore the impact of the COVID-19 pandemic on child development, education and mental wellbeing. Baseline assessment data, pre-pandemic, are already collected. Detailed information about family life in lockdown is now being collected, and follow-up assessment data will be collected when children return to school.",2020,-99,MRC Cognition and Brain Sciences Unit,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C01229,C19-IUC-092,Genetic variation and COVID-related ICU admission,"Investigating genetic variation associated with severe COVID-19 symptoms as an extension of the GenOMICC study (an open, collaborative, global community of doctors and scientists trying to understand and treat critical illness) during the SARS/MERS epidemics.",2020,-99,University of Edinburgh,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C01230,C19-IUC-175,Neutralising antibodies and protein vaccines,"Defining SARS-CoV-2-specific antibodies isolated from patients and new approaches to vaccination. These will be of value for future therapeutics, diagnostics and disease pathogenesis.",2020,-99,MRC Human Immunology Unit at the University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity, +C01231,C19-IUC-176,Protective T cell responses,"Delineating cytokines, host/viral genotype and T cell responses associated with more severe disease. This will identify high-risk groups and inform future vaccine and therapeutic development.",2020,-99,MRC Human Immunology Unit at the University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C01232,C19-IUC-177,Multi-dimensional immune responses,Investigating comprehensive immune responses in patients and during vaccine and clinical trials. These will provide early data to inform disease pathogenesis and the next steps in vaccine design and testing.,2020,-99,MRC Human Immunology Unit at the University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Clinical trial (unspecified trial phase), +C01233,C19-IUC-178,Clinical trials and immune responses in the lungs,Co-ordinating national and local clinical trial activity. Identifying early immune signals and understanding the mechanisms underlying severe forms of COVID-19 lung disease.,2020,-99,MRC Human Immunology Unit at the University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C01234,C19-IUC-179,Predicting T cell epitopes for future vaccine development,Co-ordinating the Unit's bioinformatics expertise to predict T cell epitopes that are important for future vaccine development.,2020,-99,MRC Human Immunology Unit at the University of Oxford,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies, +C01235,C19-IUC-203,Innate viral sensing,Establishing approaches to determine mechanisms of viral sensing with implications for vaccine design and disease pathogenesis.,2020,-99,MRC Human Immunology Unit at the University of Oxford,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C01236,C19-IUC-049,"ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 expression, and plasma ACE2 levels: a Mendelian randomization study.","Collaboration on project examining the impact of hypertensive drugs, statins and other co-morbidities (e.g. high BMI, Type 2 diabetes, hypertension) on the expression of receptors involved in COVID-19 infection (e.g. ACE2 and TMPRS22)",2020,-99,University of Bristol,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C01237,C19-IUC-050,Potential mechanisms of COVID-19 drug targets on other viral infection phenotypes and complex diseases,"Project to identify genetic predictors of the potential drug targets for COVID-19 from 4 recently published GWASs, and use them as instruments to systematically assess the causal effects of 378 SARS-COV-2 interacted proteins / genes on 46 infection diseases and 576 complex human diseases in 5 related human tissues using Mendelian randomization (MR). Such analysis will help evaluate the causal consequences of these genes/proteins on complex human diseases. Results of all analyses are available in an open assess online platform (www.epigraphdb.org/covid19/drug-accelerator/) to enable rapid queries.",2020,-99,University of Bristol,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01238,C19-IUC-105,RECOVERY Trial,"Leading the RECOVERY Clinical Trial for treatments for COVID-19. The UKRI/NIHR funded RECOVERY trial will test if existing or new drugs can help patients hospitalised with confirmed COVID-19. Over 175 hospitals are now involved and >12,000 patients were recruited in just a few weeks with one high-impact publication (https://www.nejm.org/doi/full/10.1056/NEJMoa2021436) and others in review.",2020,-99,University of Oxford,,Human Populations,Asian | Black | White | Unspecified,Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C01239,C19-IUC-236,Assessing trends in admissions for acute coronary syndromes in England,"Assessing trends in admissions for acute coronary syndromes - in England and Wales there has been a greater than 50% reduction in emergency department attendances for myocardial ischaemia since the start of the pandemic. Several UK cardiologists have reported a substantial reduction in demand for coronary procedures. In order to understand the scale, nature and duration of changes to admissions for different types of acute coronary syndromes, and to evaluate whether the in-hospital management of these patients was also affected as a result of the pandemic, the project will analyse data on all such admissions to NHS acute hospital Trusts in England using the Secondary Uses Service Admitted Patient Care (SUSAPC) database. Early results published online in the Lancet (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31356-8/fulltext)",2020,-99,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C01240,C19-IUC-108,Generation of MRC-PPU CVR Coronavirus Toolkit,"As a partner of the Covid-19 Protein Production Consortium (CPPC) and in collaboration with the CVR, PPU have expressed 38 proteins encoded by the viral genome and produced antibodies to them. Quality control of the antibodies is underway and these resources will be made available for the international community via new website https://mrcppu-covid.bio/. These tools can be used for a wide variety of applications.",2020,-99,MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01241,C19-IUC-109,Developing inhibitors against the crucial Nsp3 SARS-CoV-2 protease enzyme,"Characterise the papain-like cysteine protease encoded by SARS CoV2 (PLpro), that cleaves both viral polypeptide and also ubiquitin molecules from cellular targets to block viral immune responses. Structure and function analysis is being performed in order to develop inhibitors to the enzyme in collaboration with the Dundee Drug Discovery Unit.",2020,-99,MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C01242,C19-IUC-222,Re-purposing current drugs to treat COVID-19,"We are developing tests to find out whether existing drugs could quickly be repurposed to treat COVID 19. As part of a collaboration with the Francis Crick institute in London, we are developing tests for drugs that might inhibit two of the enzymes of the SARS-CoV-2 virus: one called Nsp15 (an RNase) and another called Nsp14 (a methyltransferase)",2020,-99,MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments, +C01243,C19-IUC-088,Devising new methods to detect and visualize SARSCoV2 directly in infected human tissues,"If immune cells (lymphocytes) are infected by this (SARS-CoV-2), then assumptions that patients previously infected are now immune may be incorrect. The project will devise new methods to detect and visualize SARS-CoV-2 directly in infected human tissues to determine which immune cells could be infected, which sub-class of two types of immune cells (T and B cells) are affected and which immune cells of the digestive tract may be affected. These methods will be able to confirm viral infection in deceased cases where a diagnosis was not made. _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_ _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_",2020,-99,MRC Toxicology Unit at the University of Cambridge,,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C01245,C19-IUC-022,"Tracking the virus as the pandemic progresses, including nosocomial transmissions.","Tracking the virus as the pandemic progresses, with rapid sequencing of SARS-CoV-2 from clinical samples (>800 sequences from confirmed cases so far and annotated genomes from more than >600 sequences have been made public).Development of a software package (CoV-GLUE) to track how the virus changes with time during the outbreak. A paper has also been published which details the epidemiology of seasonal coronaviruses in the context of COVID-19.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C01246,C19-IUC-023,Characterising the disease and clinical trials,"Characterising the virus to inform clinical decisions and further our understanding of the disease, by forming key partnerships such as ISARIC and participating in clinical trials to evaluate treatments such as Favipiravir and Remdesivir.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C01247,C19-IUC-025,Generating a research toolkit for the UK community and designing tools to test antiviral drugs,"Generating a research toolkit for the UK community by producing plasmids, virus isolates, antisera, reverse genetic systems, VLPs, and antibodies (in collaboration with MRC-PPU in Dundee) that will be openly shared to facilitate the work of the UK research community. Designing a variety of assays and tools to support the medium and high throughput screening of antiviral drugs to test efficacy against SARS-CoV-2.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01248,C19-IUC-026,Providing evidence for the design and refinement of COVID-19 Scottish surveillance programmes,"Providing evidence for the design and refinement of COVID-19 Scottish surveillance programmes, by estimating the level of COVID-19 infections in the community, their distribution among different age groups, and how these vary with time. This is essential to inform interventions, including the possibility of introducing ""immunological passports"" for the workforceand the easing of restrictions. The results of this project will directly inform current PHSPublic Health Scotland efforts to design a serology-based national surveillance program.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C01249,C19-IUC-196,"Enhancing capacity to understand SARS-CoV-2 infection in Africa (Kenya, The Gambia and Uganda) and globally","Providing a consortium, including the MRC/UVRI and LSHTM Uganda Research Unit and MRC Unit The Gambia,, with genomics and bioinformatics support to increase understanding of SARS-CoV-2 in Africa and to understand the evolution of the virus.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Europe,,,,United Kingdom,United Kingdom | Uganda | Gambia,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations", +C01250,C19-IUC-197,Screening existing and approved drugs and antivirals for activity against SARS-CoV-2 for rapid deployment in the clinics,Working in partnership with the University of Dundee Drug Discovery Unit to support the medium throughput screening of a selection of existing therapeutics to establish their antiviral activity against SARS-CoV-2.,2020,-99,MRC-University of Glasgow Centre for Virus Research,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C01251,C19-IUC-224,Understanding virus emergence and evolution,"Project investigating the role of zoonotic transmission in the evolution of SARS-CoV-2. Key themes include investigating the relationship of this new virus to SARS-related coronaviruses, the role of bats as a reservoir species, and the role of recombination in viral emergence.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C01252,C19-IUC-141,Impacts of restricted pre-school childcare availability,"Project to assess the impact of removing pre-school childcare on children including well-being, school-readiness and BMI as well as the impact on parents including mental health, drinking and smoking. An assessment on inequalities will be made on these outcomes by parental educations and lone parenting status.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C01253,C19-IUC-142,Impact of reducing in-person social contact on loneliness and depression among older people,Project to assess the reduction of in-person social contact and an increase of remote contact on the loneliness of elderly people as well as inequalities in loneliness and depression by education and partner status. This is intended to inform mitigation strategies.,2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions", +C01254,C19-IUC-143,Contextualise COVID-19 deaths by comparing them with other causes of death,To understand the scale of COVID-19-related deaths in the UK by comparing them to other causes of death.,2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C01256,C19-IUC-148,Association between the social determinants of health and COVID19 in informal settlements,"As part of a project led by the Liverpool School of Tropical Medicine and funded by GCRF in Sierra Leone, Kenya, India and Bangladesh, to improve state-citizen accountability and promoting equity in the well-being and health of marginalised people living in poverty in informal urban settlements. The project is now focusing its attention on determining the association between the social determinants of health and COVID-19 in informal settlements",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | South-East Asia,,,,United Kingdom,Sierra Leone | Kenya | India | Bangladesh,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities", +C01258,C19-IUC-233,Local sequencing of SARS-CoV-2 from Uganda COVID-19 cases,The project will seek to generate full virus SARS-CoV-2 genome sequences from all available COVID-19 samples,2020,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C01259,C19-IUC-235,I-COVID: The impact of COVID-19 and related public health response on vulnerable populations in Uganda,"To understand the impact of COVID-19 and related public health response on vulnerable populations, we will collect additional data from mothers and children from impoverished backgrounds and fishing communities of the EMaBS cohort, parents of children with disabilities, as well as their non-disabled peers from the EBIE study, and young sex workers of the ZETRA study, which are all ongoing studies at the MRC/UVRI & LSHTM Uganda Research Unit. Through phone interviews we assess participants' knowledge of and concerns about COVID-19, the impact of COVID-19 related public health response on participants' daily lives, and actions and recommendations for measures to reduce spread and support participants.",2020,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons | Sex workers | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C01260,C19-IUC-128,DECOVID (CMAR),"Monitoring of COVID-19 incidence in hospitals and community through PIONEER, a healthdata initiative allowing innovative healthcare companies to develop, test and deliver advances in clinical care.",2020,-99,MRC Versus Arthritis Centre for Muskuloskeletal Ageing Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C01261,C19-IUC-130,Immune response to covid19,Study to analyse the immune response over time and establish biomarkers of positive/negative outcomes. This project is funded by UKRI via the UK Coronavirus Immunology Consortium.,2020,-99,MRC Versus Arthritis Centre for Muskuloskeletal Ageing Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C01262,C19-IUC-118,Understanding virus cellular targets using the Central Laser Facility,Understanding virus cellular targets using the Central Laser Facility's Octopus Bio-Imaging Facility at Harwell,2020,-99,Research Complex at Harwell,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01263,C19-IUC-119,Analysis of SARS-CoV-2 proteins at the Diamond Light Source,Part of a collaboration to understand the receptor binding domain of the spike protein and polymerase at the Diamond Light Source at Harwell,2020,-99,Research Complex at Harwell,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01264,C19-IUC-120,"Development of nanobodies against SARS-CoV-2 spike protein for research, diagnostics and therapy","As part of Covid-19 Protein Production Consortium (CPPC), developing nanobodies against the viral spike protein for research, diagnostics and therapy at the Rosalind Franklin Institute and Protein Production UK at Harwell",2020,-99,Research Complex at Harwell,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pre-clinical studies", +C01265,C19-IUC-121,Development of software to determine protein structures by crystallography and electron microscopy,Development of software to determine protein structures by crystallography and electron microscopy,2020,-99,Research Complex at Harwell,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01266,C19-IUC-030,Development of in-house tests for immune response to Covid-19 (antibody tests),"Development of a rapid and quantitative antibody test for immune response to COVID-19, which will be used to help select donors for plasma immunotherapy from individuals who have recovered from COVID-19",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity, +C01267,C19-IUC-031,Clinical characterisation: Does SARS-CoV-2 injure the brain?,"Clinical characterisation of the neurological and cognitive effects of SARS-CoV-2 linked brain injury, by examining CNS effects of SARS-CoV-2 in an international collaborative effort to identify the frequency of such symptoms and how these can be detected, predicted, monitored and, potentially, treated. Project will include comparing cerebrospinal fluid/blood biomarker profiles for neuronal injury and neuroinflammation between COVID-19 positive patients with and without neurological symptoms.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C01268,C19-IUC-032,Control and mitigation - Covid-19 Monitoring Protocol,"The UK DRI Care Research & Technology centre is adapting its 'Healthy Homes' programme, which uses remote technology to monitor the physiology and behaviour of around 100 people with dementia and their carers in their homes. Data is shared with a clinical team for rapid intervention aimed at reducing unplanned hospital admission. A new protocol has been introduced specifically to monitor for early symptoms of Covid-19.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C01269,C19-IUC-034,Epidemiology - Patient bioresource and database,Formation of a patient bioresource and database on all patients with either suspected or confirmed COVID-19 infection presenting to the Imperial NHS Trust (through the Imperial Health Knowledge Bank) and coordinate that with national efforts BioAid and ISARIC in order to discover new prognostic and diagnostic biomarkers and tests. Specific efforts are underway to obtain olfactory epithelia and brainstem on a limited number of patients dying of COVID-19 to test hypotheses regarding neurotropism of virus.,2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis", +C01270,C19-IUC-035,Impact of COVID-19 on chronically immunosuppressed neurological patients,Impact of COVID-19 on chronically immunosuppressed neurological patients as an extension of an ongoing pharmacovigilance study of people with multiple sclerosis eligible for treatment. We will assess the impact of chronic immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (OPTIMISE) with an extended focus on collection of COVID-19 related morbidity data collection. The aim is to assess the differential risk of infection with DMT and estimate the relative risks with alternative DMT.,2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis, +C01271,C19-IUC-036,UK DRI-DZNE Collaboration for development of personalised risk models for COVID-19 infection and severity,"Collaboration for development of personalised risk models for COVID-19 infection and severity, by coordinating a small international data science group to prospectively gather COVID-19 healthcare data (updated weekly now) from UK Biobank (and Quebec, CA) over the next year for linkage to genetics, clinical history and environment/lifestyle data for personalisation of the risk of disease and severity. The results will help develop a refined risk profile for COVID-19 infection while exploring the genetic factors associated with infection risk and virulence.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom,United Kingdom | Canada,Epidemiological studies,Disease susceptibility, +C01272,C19-IUC-081,Identifying gene/protein signatures associated with poor disease outcome,Identifying gene/protein signatures associated with poor disease outcome at the time of hospital admission through single cell analysis to allow focussing of resources on the most at risk patients.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C01273,C19-IUC-082,Cardiovascular response in COVID-19,Cardiovascular dysfunction in COVID-19 will be investigated in vitro using human embryonic stem cell derived-cardiomyocyte and vascular cell models. Examining viral proteins and pseudotypes in to human cardiomyocytes and vascular cells and ways this can be modulated by modifying the ACE2 viral receptor or accessory proteases such as TMPRSS2. The project will also study the effects of the immune response on these cells.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity", +C01274,C19-IUC-083,Recruitment and requirement of host RNA binding proteins by SARS-CoV-2 during infection cycle and potential for new therapeutic targets,Recruitment and requirement of host RNA binding proteins by SARS-CoV-2 during infection cycle and potential for new therapeutic targets. The information will be used for selective targeting of viral replication with repurposed drugs.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01275,C19-IUC-085,Developing an in vitro platform to screen therapeutic agents,Developing an in vitro platform to screen therapeutic agents by exploring the hypothesis that infection of cholangiocytes (which express ACE2 receptor) may mediate hepatic dysfunction associated with virus infection. Developing an in vitro platform using primary cholangiocytes as organoids to screen therapeutic agents for their capacity to inhibit viral entry and study the mechanisms by which SARS-COV2 enter cells.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01276,C19-IUC-220,Investigating viral interactions with megakaryocytes,Looking at the effect on platelet release and function because abnormal blood clotting is an important feature in very ill patients. The team will generate stocks of frozen megakaryocytes to send to collaborators in Bristol.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis", +C01277,C19-IUC-221,"Identifying genetic and structural similarities between SARS-CoV-2, the coronavirus that causes COVID-19, and measles, mumps, and rubella (MMR).","The team have found key structural similarities between the coronavirus and the rubella virus - in the Macro domain, almost a third (29%) of the amino acids were the same for both viruses. The team put forward a hypothesis in a pre-print on Medrxiv that MMR could offer some protection to vulnerable groups against poor outcomes in COVID-19 infection.",2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01278,MR/N020413/1,"Applications of Mass Spectrometry to Membrane Protein Drug Development, to address urgent work on COVID-19","Impact/national response: our aim is to accelerate effective drug development and provide critical data rapidly for continued research. We will determine novel chemical matter for further development, identify existing drugs for repurposing and highlight off-target drug binding Urgency: The type of data we are able to generate is needed now to feed into drug discovery programmes; it cannot be obtained through other experimental platforms in the same timescale (6 months)Our approach: we will probe associations in viral assembly and cellular entry pathways using our bespoke massspectrometry (MS) platform (Nature Methods in press). We will monitor the oligomeric status of proteins their ligand binding capacity and PTM status within individual experiments.Objective 1: inhibit Mpro through disruption of the monomer dimer interface.Mpro, a key CoV enzyme, mediates viral replication and transcription. Mpro shares considerable homology withMERS-CoV Mpro which showed substrate-induced dimerization with proteolytic activity. We have proof-ofconceptdata that show the monomer-dimer equilibrium enabling us to screen to disrupt dimer interactionsusing our unique MS platform.Objective 2: understand antigen processing and interactionsPrevious SARS-CoV infections suggest that glycosylation of a specific residue abrogates S protein binding implyingthat interfering with glycosylation could impede recognition. We will investigate how S protein glycans affectassociations with ACE2 to inform design of glycoprotein processing inhibitors.Objective 3: characterise the oligomeric states and binding sites of ACE2The SLC B0AT1 supports dimerization of ACE2. How do lipids, proteases (TMPRSS2) and other small moleculesregulate its activity? We will apply MS-based methods, optimized to study membrane proteins, protein-protein,and protein-ligand interactions to this complex.Feasibility/Critical mass: All proteins are available immediately through collaboration with the SGC Oxford. Wealso have unique chemical libraries that can be deployed for this project as well as bespoke instrumentation. Ourdepartment is open for COVID-19 work only. I have secured permission for access and have engaged a dedicatedteam of highly experienced researchers.Accessibility: High-throughput screens using X-ray structures are ongoing in Oxford and feed into the COVID-19Therapeutics Accelerator Consortium. We will communicate all our findings immediately to this, and other localand national initiatives, including national repositories where they can be accessed immediately. Wherepertinent, these (and other) findings will also be communicated to decision makers through my role as Presidentof the Royal Society of Chemistry.",2020,2021,University of Oxford,340060.6,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2016 +C01279,C19-IUC-006,Antigens as vaccine candidates and for serological testing,Developing effective antigens based on viral spike proteins and nucleoprotein for use as vaccine candidates or in immunological tests to determine if patients have been infected with SARS-CoV-2 already.,2020,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies", +C01280,C19-IUC-007,ACE2 decoys,"Developing 'decoy' molecules that can bind to the virus and reduce its ability to enter cells, with potential to be used as an emergency therapy as an alternative to antibodies.",2020,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Prophylactic use of treatments", +C01281,C19-IUC-008,High-resolution virus structure,"High resolution imaging of parts of the virus in order to aid a deeper understanding of the molecular processes that occur during infection. Images include the SARS-CoV-2 virus, key viral proteins (S protein) bound to the ACE2 receptor, along with the binding of neutralising antibodies.",2020,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01283,C19-IUC-010,S2m RNA elements,Characterising the role of an evolutionary conserved RNA element in stabilising viral transcripts - a potential target for RNA-directed therapeutics.,2020,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C01284,C19-IUC-012,Processing of SARS-CoV-2 multiproteins,Mechanistic understanding of how chloroquine acts against COVID-19 infection by affecting the transport of proteins within the cell.,2020,-99,MRC Laboratory of Molecular Biology,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01286,C19-IUC-260,Drug screening platform,Generation and distribution of an efficient drug screening platform for inhibitors of SARS-CoV2 cell entry.,2020,-99,MRC Laboratory of Molecular Biology,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01287,C19-IUC-261,Phage-based SARS-CoV-2 assay,"Development of a cheap, rapid and easily-scalable phage-based assay for detection and analysis of patient anti-SARS-CoV-2 antibody responses, as an alternative to current antibody assays.",2020,-99,MRC Laboratory of Molecular Biology,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C01289,C19-IUC-253,THEME 2 - COVID-19 immunity and immunopathology,"Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes. Theme 2 is ""Immunity and immunopathology - testing and mechanisms"", how can we tell who's already had the virus and why are some cases so much worse than others? Setting up several serological platforms to enable the testing for prevalence of infection in the population and to determine correlates for protection. These will be developed for simultaneous detection of antibodies to understand which immune parameters are adequately predictive.",2020,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Immunity | Disease surveillance & mapping, +C01290,C19-IUC-254,THEME 3 - COVID-19 molecular mechanisms and target identification,"Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes. Theme 3 is ""Molecular mechanisms and target identification"", how does the virus infect our cells and how can we use this information to identify potential treatments? Aiming to define and validate tractable antiviral drug targets and providing assays for others working in this field. The focus will be on 1. Virus-cell surface interactions which could translate into diagnostic tests for neutralising antibodies, 2. Viral entry, generating mutants with fluorescent markers to understand the viral lifecycle and 3. Virus replication, transcription and translation for mechanistic insights.",2020,-99,Francis Crick Institute,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations", +C01291,C19-IUC-255,THEME 4 - Clinical epidemiology and management in healthy subjects,"Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes. Theme 4 is ""Clinical epidemiology and clinical management in well subjects"", how is coronavirus transmitted and is it evolving? Can lifestyle and ethnicity make the disease more severe? Applying molecular viral typing to trace the transmission of SARS-CoV-2 viral strains and correlating data on infection with individual parameters of susceptibility in order to better understand the factors that define viral spread in different settings. Focus of work will be on 1. Viral transmission and evolution, 2. Influence of the host immune response on disease outcome and 3. Mechanisms of viral-induced organ damage and death.",2020,-99,Francis Crick Institute,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C01292,C19-IUC-256,THEME 5 - Clinical epidemiology and management in vulnerable populations,"Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes. Theme 5 is ""Clinical epidemiology and clinical management in vulnerable populations"", how is coronavirus affecting cancer treatment and vulnerable people who need medical care? Aiming to understand the specific risks for vulnerable populations, including the interaction of SARS-CoV-2 infection with different types of cancer and with specific treatment modalities. This will address, 1. The impact of underlying health conditions, such as cancer, on the course of COVID-19, 2. The impact of anti-cancer interventions on the course of COVID-19 and 3. Protecting vulnerable populations in hospital by using large cohorts of cancer patients and associated healthcare works to study transmission dynamics.",2020,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C01293,MR/S000208/1,Investigation of the generation and functional maturation of regulatory T cells in vivo,"This important study will explore T-cell immunity to COVID-19. T-cell immunity is considered to play key roles in the eradication of infection by promoting B-cell maturation and eliciting cytotoxic activities to the virus. It is also known that severe COVID-19 patients show remarkable T-cell dysregulation. However, it is unknown known how T-cells respond to each of the key COVID-19 viral antigens, and there is still an urgent need for basic research on the antiviral T-cell immunity using animal models. Accordingly, I propose to investigate T-cell responses to the key COVID viral antigens (including Spike protein) using our mouse models. Specifically we will test if each of the viral proteins induces a particular type of T-cell responses (e.g. Th1 response, Treg induction). We will analyse not only regulatory T-cell (Treg) responses but also helper T-cell responses and CD8+ T-cell responses to the antigen. We will produce recombinant proteins and perform DNA vaccination to analyse T-cell responses. Nr4a3-Tocky and Foxp3-Tocky, which allow the analysis of antigen-reactive T-cells and Treg dynamics, respectively. The level of urgency and importance The proposed project will produce basic materials and knowledge for (1) improving vaccine strategies by enhancing T-cell immunity; (2) improving the COVID-19 immunity test. The fund by converting the two original activities into the COVID-19 research will be equivalent to a 6-month project. We will apply for a follow-on fund through the UKRI and/or industrial grants, in order to further investigate anti-COVID-19 T-cell immunity and develop new methods for fighting COVID-19. The necessary critical mass: The proposed project will be still within the scope of the original plans, i.e. to investigate the mechanism of the generation and functional maturation of Treg in vivo. Instead of using other antigen models, we will use the viral antigens. Thus, we have all the resources including the key transgenic mouse tools (Foxp3-Tocky and Nr4a3-Tocky mice) for the investigation. We will use a commercial maintenance service and their technical supports for maintaining and obtaining the Tocky mice for experiments, in order to smoothly conduct the planned experiments. Strengths: The proposed project will provide key preliminary data for further developing new methods to improve COVID-19 vaccines and immunity tests.",2020,2022,Imperial College London,100802.96,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2019 +C01294,MR/S004688/1,Adhesion to host cell membrane microdomains in cornea as an antimicrobial target to prevent corneal ulceration,"This award, made jointly to The University of Sheffield, UK and LV Prasad Eye Institute, India, isaimed at the development of inhibitors of microbial adhesion to host cells based on the sequence ofa human protein, tetraspanin CD9. A key discovery that we have made during the tenure of thisaward, is that the mechanism of action of the peptides is highly likely to be the dispersal of heparansulphate-bearing proteins at the host cell surface. These proteins (e.g. syndecan-1) are usuallylocated in tetraspanin-enriched microdomains (TEM). CD9 is found at high levels on most epithelialsurfaces and is a critical component of TEM in these cells. We have shown that many types ofpathogenic bacteria, and some fungi, use heparan sulphates as an adhesion platform, allowing theirattachment to host cells to enable later events, such as internalisation and transcytosis acrossepithelial layers. CD9 peptides and heparin, a soluble analogue of heparan sulphate, give identicalinhibition of bacterial attachment.We note that some viruses, e.g. herpes simplex, also use heparan sulphates during cell attachment.Coronaviruses such as human NL63, OC43 and SARS-CoV, have also been reported to adhere toheparan sulphates. The furin cleavage motif (RRXRR) found in several human coronaviruses stronglyresembles a heparan sulphate binding motif (XBBXBX or XBBBXXBX). In SARS-CoV-2, the putativefurin site is PRRARSV and is thought to be an important adaption that allowed the transfer ofvirulence between animals and humans.In preliminary work, we have shown that SARS-CoV-2 spike protein (containing S1 and S2 domains)binds strongly to the human RT4 epithelial cell line that expresses low levels of receptor ACE2 andproteases TMPRSS2 and ADAM17. In contrast, recombinant S1 domain, a smaller fragment of S1containing only the receptor-binding domain and a mutant form of S1S2 spike protein that lacks thefurin cleavage site, bind at very low levels. Unfractionated heparin, at 0.1U/ml, can inhibit wild typeS1S2 binding, reducing it to the very low levels detected for the other spike proteins. Surfen, aheparan sulphate binding aminoquinoline, can also inhibit S1S2 binding.We interpret these data as an indication that SARS-CoV-2 has a high affinity for heparan sulphates,and that this interaction with the host cell surface can occur in cell lines with only minimal ACE2expression. Heparan sulphates may therefore be important in the retention of virus at an epithelialsurface prior to internalisation and infection via ACE2, a protein paradoxically found only at lowlevels in airway epithelia. Heparin may inhibit this interaction, and so lower the rate of infection. Wenote that low molecular weight heparin (LMWH) is already used therapeutically with some successin late stage Covid-19 patients to treat hypercoagulation.We would therefore like to repurpose this award to allow us to make a fuller investigation of SARSCoV-2 use of heparan sulphates before alerting clinicians to the possibility that heparin or LMWHtreatment earlier in Covid-19, perhaps even before blood clotting disorders develop, would bebeneficial. There are also heparin analogues and heparan sulphate antagonists that have been usedclinically for other indications (e.g. Fondaparinux, Ciraparantag) that we would like to test forinhibition of S1S2 binding. Finally, we would like to be able to test (by collaboration) the effects ofheparin and analogues in a live virus infection assay. We envisage that this work will take 4-6 weeks,enabling the full resources of the MRC award to be used in Sheffield: at least part-time effort byPDRA, technician and the associated PhD student, funding for drug synthesis and the purchase ofrecombinant viral proteins. During this period, we would apply to the UKRI Rapid Response Call forfurther funding to help transfer this research into clinical practice.This work would make minimal impact on the original aims of the award, as we are currently unableto make progress in the UK or India. It will also feedback into the original award because we wouldalso be able to test Surfen, Fondaparinux and Ciraparantag, etc as inhibitors of bacterial infection.",2020,2021,University of Sheffield,388638.75,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,United Kingdom | India,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2018 +C01295,MC_PC_20009,MRC contribution towards the EDCTP COVID-19 emergency call for proposals (Mobilisation of funding for COVID-19 research in sub-Saharan Africa research),"The MRC contribution (and that of DHSC UK total €3.5m Total funding €10m ) supports the UK participants in the awarded studies. Following the novel Coronavirus disease (COVID-19) outbreak in December 2019, there has been an unprecedented rapid spread across more than 181 countries, with more than 1 million confirmed cases globally as of 3 April 2020. In the light of rising numbers of cases being reported from affected countries, including several sub-Saharan African countries, the EDCTP Association agreed to activate the emergency funding mechanism to support Research & Innovation Actions (RIAs) as part of the European response to the COVID-19 emergency.",2020,2021,European & Developing Countries Clinical Trials Partnership,2454000,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Netherlands,United Kingdom,,,2020 +C01296,MR/V009761/1,"Mathematical modeling and adaptive control to inform real time decision making for the COVID-19 pandemic at the local, regional and national scale","Emergence of a novel strain of coronavirus in the city of Wuhan in China resulted in a global pandemic and the implementation of social distancing measures in a significant number of countries around the world in order to reduce the risk to the most vulnerable members of society. The first case of infection in the UK was reported on 31st January 2020 and with cases continuing to rise, the country was put into lockdown on 23rd March in an effort to reduce the spread of disease.Throughout the epidemic in the UK, mathematical models (including predictions from Warwick) have been used to provide support to the government and to guide decision making. However, these models are typically required to repeatedly produce new outputs as more data emerges on a daily basis on cases and deaths, and there is a need to investigate how the predictions are likely to change as more data become available.This project will develop methodology that will allow for robust parameter inference of the Warwick model, which is already being used for UK-decision support. We will enhance our real time model fitting, incorporating up to date information on cases and outcomes, and use this framework to determine multi-phase adaptive control policies, with a focus upon optimal timing of relaxation and tightening of social distancing measures, that should be implemented to mitigate future infection waves. Our results will be communicated directly to the scientific pandemic influenza modelling group that advises the UK government.",2020,2021,University of Warwick,149161.48,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C01297,MR/V012908/1,"Rapid evaluation of the COVID-19 pandemic response in palliative and end of life care: national delivery, workforce and symptom management (CovPall)","The COVID-19 pandemic is placing an unprecedented strain on health care services. Although many people survive, an estimated 1 to 4% die from this disease. There are more than 10,000 UK deaths from COVID-19, with numbers escalating. Many of the symptoms, such as breathlessness, fever, agitation and pain, are very distressing. But in this new disease these symptoms are not well understood. Palliative care services are adapting rapidly to this situation, but in different ways, not knowing what is best. This research aims to rapidly evaluate the palliative care response in COVID-19 to improve care now and in the future. There are two main components, called work packages (WPs), to the research. WP1 surveys, UK wide, palliative care medical or nursing leads, about their changes in practice, how they deploy the workforce, volunteers and technology, their innovations and challenges. WP2 collects data about patients' symptoms, how they change over time, and the effects of treatments. We collect this information immediately and quickly (phase I), and then repeat the data collection after 6-8 weeks (phase II) to understand how practice is changing. We involve patients, families, the public, policy makers and services in all stages of the research. We release early findings, to help catalyse an effective response.",2020,2021,King's College London,172361.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,Disease pathogenesis | Health service delivery | Health workforce,2020 +C01298,MC_PC_20006,mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 - Repurposed Drugs (TACTIC-R),"The COVID-19 pandemic, declared on 11th March 2020 by the World Health Organisation (WHO), is caused by a novel coronavirus (SARS-Cov-2). In the UK by 3rd May 2020, 185,599 cases had a laboratory-confirmed diagnosis and SARS-Cov-2 associated deaths totalled 28,446. The majority of individuals infected with SARS-Cov-2 have mild/moderate symptoms, but 15% have severe disease and there is 1% mortality. Several risk factors for adverse outcomes have been identified, although their interaction with the disease course is not understood. SARS-Cov-2 causes acute respiratory distress syndrome, which can lead to multi-organ failure and death. There are no vaccines and one drug therapy, remdesivir, that has just received regulatory approval. Severe organ damage is accompanied by a dysregulated inflammatory hyperactivation syndrome with high levels of IL-6, TNF-alpha, IL-1-beta, and influx of neutrophils and cytotoxic T cells. Activation of the coagulation and complement cascades results in amplification of the inflammatory response culminating in tissue cytotoxicity and, and micro thrombosis.TACTIC addresses the hypothesis that immunomodulation of hospitalised patients at high risk of a severe diseasecourse will increase the time to mechanical ventilation, other vital organ failure or death. Eligible patients will be18 years or older with suspected SARS-Cov-2 infection who have been admitted to hospital and score at least 3 points in an 8 point risk score that includes radiologic, demographic and laboratory criteria.Patients will be randomised 1:1:1 to open label ravulizumab (anti-complement C5 monoclonal antibody, Alexion),baricitinib (oral JAK inhibitor, Lilly) or standard of care alone. The treatment duration will be from entry to discharge, to 14 days or until the primary end-point is reached. Following hospital discharge, patients will have telephone follow-up at 28 and 90 days. Those receiving ravulizumab will require antibiotic prophylaxis and meningococcal vaccination after discharge. Termination of treatment groups and addition of further interventions will follow recommendations by the Independent Data Monitoring Committee. A planned interim analysis will occur when approximately 125 patients/group have been recruited. Recruitment of potentially effective therapies will continue until 229-469 patients/group, based on a frequentist hypothesis. Bayesian posterior distributions will inform the advice of the IDMC. A key sub-hypothesis is that predictive biomarkers for drug response can be identified, and a parallel biomarker program involving the NIHR bioresource has been developed.",2020,2021,University of Cambridge,858544.17,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C01299,MC_PC_20007,CATALYST a randomised early phase adaptive trial for new drugs for SARS-CoV-2+ patients,"CATALYST is a randomised, open-label, multi-arm, adaptive, phase II trial to assess the potential efficacy of drugs in the early phase setting, rapidly determining which new therapies should be considered for larger-scale testing within ongoing national phase III platform trials. SARS-CoV-2 virus can cause severe pneumonia and multi-organ failure by sequestration of virally-infected pulmonary and circulating macrophages, dendritic cells and abnormal antibody response to viral antigens, which promote an injurious, proinflammatory microenvironment. Licensed and novel drugs are now available with potential to target this harmful proinflammatory response and/or directly act as antivirals, allowing a healthy adaptive immunity to emerge to suppress the viral infection and reduce viral replication respectively. The primary outcome measure, the ratio of oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2), will be modelled using Bayesian multi-level models that allow for nesting of the repeated measures data. Specifically, posterior probabilities for the treatment and treatment/time interaction covariates will be used to conduct decision making. Data will be analysed in subsets; each treatment against the control group, with modelling conducted on each dataset. Any important covariates will be incorporated accordingly into the model structure. All comparisons will be performed with regard to control arm data.",2020,2021,University of Birmingham,552150,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C01300,UK CPPC,The COVID-19 Protein Portal,"The COVID-19 Protein Portal allows UK scientists to access protein reagents for critical research relating to SARS-CoV-2. Protein reagents are provided free of charge by a consortium of leading protein production laboratories, in an Open Science initiative led by Wellcome and UKRI.In response to the urgent need for COVID-19 therapeutics, vaccines and diagnostics, many expert UK scientists are working to understand the fundamental biology of SARS-CoV-2. Reliable robust protein reagents are crucial to such research, but can be challenging and time consuming to produce, especially under restricted working conditions.To facilitate vital research on SARS-CoV-2, Wellcome and UKRI have brought together a consortium of leading centres of protein engineering and production to launch the COVID-19 Protein Portal. The COVID-19 Protein Production Consortium (CPPC) is made up of expert scientists from founding institutes including Diamond Light Source, the Rosalind Franklin Institute, the Francis Crick Institute, the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) and MRC Laboratory of Molecular Biology (MRC-LMB), the Edinburgh Protein Production Facility, STRUBI and the Structural Genomics Consortium; with logistical support from Instruct-ERIC.The CPPC will produce and provide access to protein reagents through the COVID-19 Protein Portal website at [http://COVID19proteinportal.org]. The Portal contains a searchable database of reagents, including viral proteins, human proteins and antibodies relevant for SARS-CoV-2 biology. Each reagent is annotated with key information, including sequence, origin, and SDS-page results post purification. Researchers are able to select the proteins they require from the database and submit their request with a short research proposal. All requests will be subject to rapid peer review, to enable the CPPC to coordinate and prioritise reagent allocation based on scientific merit and the urgency of the request. Once approved, a request will be allocated to one of the CPPC's expert protein production laboratories, all of whom are committed to providing high-quality reagents as quickly as possible.In the spirit of Open Science, recipient labs will be required to provide feedback to the CPPC on their experiments, and to share important outcomes with the scientific community. By contributing to the coordination of research efforts across the UK, the COVID-19 Protein Portal will accelerate vital research to deliver effective clinical management of COVID-19.",2020,2021,"Numerous including MRC, EPSRC and Wellcome Trust Institutes",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems | Health leadership and governance,2020 +C01301,EP/V009486/1,Enhancing facemask effectiveness during the COVID-19 pandemic through the development of personalised additively manufactured PPE,"This project brings together digitial facial profiling with advanced additive manufacturing of medical grade silicones to improve the effectiveness of facemasks for key workers during the COVID-19 crisis. Customisation of FFP3 standard facemasks, whether generic or those being developed through alternative manufacturing routes to address the global supply shortage, is urgently required to (i) provide an effective seal protecting workers against viral transmission and (ii) enhance wearability to prevent skin trauma that is associated with prolonged use. In this project we will firstly assess the suitability of using smart phone based 3D imaging technologies to capture facial form and compare this data with clinically used photogrammetry. Simultaneously we will develop and assess a range of custom silicone interface prototypes that can be applied to existing FFP3 masks and newly developed designs. To achieve this we will use our existing expertise of 3D printing silicone to systematically optimise compositions tailored for this application exploring rheological and deposition variables. Our aim is to rapidly progress to mask 'fit' checking according to standard clinical procedures, evaluating for superiority in seal, comfort and reduced fitting time. Efficacy of viral disinfection of the additively manufactured silicone interfaces will also be assessed to facilitate translation. End-users will take an active part in the project, which itself will be supported by institutional research and development / commercialisation teams to maximise the chance of scale-up at the earliest timepoint.",2020,2021,King's College London,193220.6,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C01302,EP/M005089/1,SIPHS: Semantic interpretation of personal health messages for generating public health summaries,"Open online data such as microblogs and discussion board messages have the potential to be an incredibly valuable source of information about health in populations. Such data has been rapidly growing, is low cost, real-time and seems likely to cover a significant proportion of the demographic. To take two examples, PatientsLikeMe has enjoyed 10% growth and now has over 200,000 users covering over 1500 health conditions; the generic Twitter service is expanding at a rate of 30% annually with over 200 million active users. Going beyond simple keyword search and harnessing this data for public health represents both an opportunity and a challenge to natural language processing (NLP). This fellowship proposal is about helping health experts leverage social media for their own clinical and scientific studies through automatic techniques that encode messages according to a machine understandable semantic representation. There are three major challenges this project seeks to address: (1) knowledge brokering: to develop algorithms to identify and code the informal descriptions of conditions, treatments, medications, behaviours and attitudes to standard ontologies such as the UMLS; (2) knowledge management: to create a structured resource of patient vocabulary used in blog texts and link it to existing coding systems; and (3) adding insight to evidence: to work with domain experts to utilize the coded information to automatically generate meaningful summaries for follow up investigation. At the technological level the fellowship seeks to pioneer new methods for NLP and machine learning (ML). Social media remains a challenging area for NLP for a variety of reasons: short de-contextualised messages, high levels of ambiguity/out of vocabulary words, use of slang and an evolving vocabulary, as well as inherent bias towards sensational topics. The fellowship seeks to harness the progress made so far in NLP for social media analysis in the commercial domain and develop it further to provide meaningful public health evidence. One key aspect not previously addressed is in the clinical coding of patient messages. Although knowledge brokering systems exist for clinical and scientific texts (e.g. the NLM's MetaMap), their performance on social media messages has been poor. The fellowship will utilise the rich availability of ontological resources in biomedicine together with ML on annotated message data to disambiguate informal language. Research will also aim to understanding the communicative function of messages, for example whether the message reports direct experience or is related to news, humour or marketing. If these problems are successfully overcome an important barrier to data integration with other types of clinical data will be removed. The advantage of providing health coding for social media reports is its potential for studying very-large scale cohorts and also in real-time early alerting of aberrations. In the fellowship I will research the potential for multi-variate time series alerting from semantically coded features, working with domain experts to evaluate across a range of metrics (e.g. sensitivity, timeliness, false alerting rates). A variety of approaches will be explored to generate real time risk summaries across social media sources. Two real-world applications have been chosen to take this forwards: early alerting for Adverse drug reactions (ADRs) and Infectious disease surveillance (IDS). Project outcomes will include fundamental technologies as well as open source algorithms, data sets and ontology. An exciting aspect of this fellowship is inter-disciplinary collaboration across stakeholders at all levels: scientists, public health experts and industry. Finally, participation will be opened up to the international community through the release of open source data. Colleagues working on social media technologies will be invited to participate in discussions with users at a new challenge evaluation workshop.",2020,2020,University of Cambridge,1192587.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health | Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Communication | Health service delivery,2015 +C01303,EP/N014499/1,EPSRC Centre for New Mathematical Sciences Capabilities for Healthcare Technologies,"As quality of life constantly improves, the average lifespan will continue to increase. Underlining this improvement is the vast amount of the UK government's support to NHS (£133.5 billion in year 2011/12) and the UK pharmaceutical industry's R&D large investment (4.9 billion to R&D in year 2011/12). The expectation of quality healthcare is inevitably high from all stakeholders. Fortunately recent advances in science and technology have enabled us to work towards personalised medicine and preventative care. This approach calls for a collective effort of researchers from a vast spectrum of specialised subjects. Advances in science and engineering is often accompanied by major development of mathematical sciences, as the latter underpin all other sciences. The UoL Centre will consist of a large and multidisciplinary team of applied and pure mathematicians, and statisticians together with healthcare researchers, clinicians and industrialists, collaborating with 15 HEIs and 40 NHS trusts plus other industrial partners and including our strongest groups: MRC Centre in Drug Safety Science, Centre for Cell imaging (CCI for live 3D and 4D imaging), Centre for Mathematical Imaging Techniques (unique in UK), Liverpool Biomedical EM unit, MRC Regenerative Medicine Hub, NIHR Health Protection Research Units, MRC Hub for Trials Methodology Research. Several research themes are highlighted below: Firstly, an improved understanding of the interaction dynamics of cells and tissues is crucial to developing effective future cures for cancer. Much of the current work is in 2D, with restrictive assumptions and without access to real data for modelling. We shall use the unparalleled real data of cell interactions in a 3D setting, generated at UoL's CCI. The real-life images obtained will have low contrast and noise and they will be analysed and enhanced by our imaging team through developing accurate and high resolution imaging models. The main imaging tools needed are segmentation methods (identifying objects such as cells and tissues regions in terms of sizes, shapes and precise boundaries). We shall propose and study a class of new 3D models, using our imaging data and analysis tools, to investigate and predict the spatial-temporal dynamics. Secondly, better models of how drugs are delivered to cells in tissues will improve personalised predictions of drug toxicity. We shall combine novel-imaging data of drug penetration into 3D experimental model systems with multi-scale mathematical models which scale-up from the level of cells to these model systems, with the ultimate aim of making better in-vitro to in-vivo predictions. Thirdly, there exist many competing models and software for imaging processing. However, for real images that have noise and are of low contrast, few methods are robust and accurate. To improve the modelling, applied and pure mathematicians team up to consider using more sophisticated tools of hyperbolic geometry and Riemann surfaces and fractional calculus to meet the demand for accuracy, and, applied mathematicians and statisticians will team up to design better data fidelity terms to model image discrepancies. Fourthly, resistance to current antibiotics means that previously treatable diseases are becoming deadly again. To understand and mitigate this, a better understanding is needed for how this resistance builds up across the human interaction networks and how it depends on antibiotic prescribing practices. To understand these scenarios, the mathematics competition in heterogeneous environments needs to be better understood. Our team links mathematical experts in analysing dynamical systems with experts in antimicrobial resistance and GPs to determine strategies that will mitigate or slow the development of anti-microbial resistance. Our research themes are aligned with, and will add value to, existing and current UoL and Research Council strategic investments, activities and future plans.",2020,2020,University of Liverpool,2459273.65,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Other | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies | Approaches to public health interventions,2015 +C01305,EP/P010024/1,"GrantSCAMPI: Self-Care Advice, Monitoring, Planning and Intervention","In order to relieve pressure on an increasingly overstretched NHS, there is an ever-growing need to deliver more efficient, effective, patient-centric care in the community. New intelligent healthcare technologies have the potential to deliver this care relieve the pressure, in the form of simple-to-use digital technologies in people's home that support self-care and reduce the need for routine interventions from healthcare professionals. Therefore, the SCAMPI consortium will develop a new form of computerised toolkit that will allow someone living in their own home with a chronic condition, together with their relatives, carers and healthcare professionals, to self-manage both their care of the condition and life with it. People will interact with the new toolkit through a new form of intelligent visual care plan, called VIZ-CARE. Any care plan is a documented agreement between a patient and healthcare professionals about the patient's care goals and qualities to maintain or work towards, and the desired services, medicines, and activities such as eating, exercising and socialising. SCAMPI's new form of care plan will be visual, natural and simple-to-use, enabling a person living at home with a chronic condition to customise their life and care according to their individual needs and preferences, with pro-active support for thinking about important care goals and qualities, as well as the means to achieve those goals and qualities. The person using VIZ-CARE will also be able to share the plan with named relatives, their carers and targeted healthcare professionals such as specialist nurses and their GPs, and make joint decisions about customising the care plan so that the person's needs can be met more effectively, even when these other people are elsewhere, using web technologies. Moreover, the visual care plan will update regularly with care-specific feedback from discrete and cost-effective sensor devices placed around the person's home. Using the available data from these sensors as input to different artificial intelligence algorithms, a person's visual care plan in VIZ-CARE will indicate the degree to which the care goals and qualities of the person as specified in the plan are being achieved, and if needed, flag potential risk indicators along with care recommendations when a goal or quality is not being achieved. For example, to monitor planned daily activities such as a 20-minute local walk, VIZ-CARE will collect data not only about walking using a device such as a pedometer, but also about life and care qualities specific to the person and dependent on good hydration associated with walking about weight loss (from scales), movement in the home (to detect disorientation), kitchen temperature (to detect food consumption), loss of energy (from bed sensors) and water usage (from tap meters), and generate risks warnings if needed. This intelligence-led feedback is predicted to support self-care and reduce the need for routine interventions from healthcare professionals in the management of chronic conditions. To develop and evaluate this new computerised toolkit, leading researchers in computer science, the health sciences and digital business at City University London have joined forces. The team will develop the first version of the toolkit to support with people with two conditions - dementia and Parkinson's disease. And to engage people with these conditions, their families, carers and disease experts in the co-design and evaluation of the toolkit, the researchers will work closely with the Alzheimer's Society and Parkinson's UK. Moreover, to maximise impact from SCAMPI, the team will work with 6 London-based Care Commissioning Groups (CCGs) - Sutton CCG and the CWHHE Collaborative of 5 CCGs. Digital entrepreneurs Evalucom Consulting will seek to commercialise the research results so that the elements of the toolkit can be made quickly and widely available.",2020,2020,University of London City,1234364.45,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Unspecified,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health | Innovation,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2017 +C01306,EP/P023444/1,Personalised Simulation Technologies for Optimising Treatment in the Intensive Care Unit: Realising Industrial and Medical Applications,"In the UK, approximately 142,000 people are admitted to Intensive Care Units (ICU) each year. A large proportion of these patients have life-threatening pulmonary illness and require mechanical ventilation; the mortality rate in this group is around 35%, and even survival may bring ongoing suffering lasting years after discharge. Critical pulmonary disease thus has enormous financial impact and represents a significant burden of suffering for the general population. Despite years of research, there has been a lack of progress in our understanding of critical illness and in our ability to personalise treatment. Traditional clinical research approaches (using randomised clinical trials) have been costly and often inconclusive, and have provided disappointing improvements in critical care (diagnosis, survival, cost-effectiveness). The development of more effective personalised treatments for this patient population would therefore have significant national and global impact. In this project, we will develop novel methods for personalising and optimising the therapy delivered in the ICU. We will work closely with our business and clinical partners to transfer our high-fidelity modelling technologies from the research lab to the ICU, in order that real-time, personalised, patient simulation can be achieved with the aim of guiding the treatment of critical illness. This approach offers potentially ""low-cost"" improvements in patient-care, since it is based on smarter strategies and technologies that exploit and optimise multiple interventions, without requiring expensive new pharmaceuticals or devices. Using large-scale integration of incoming data streams from routine patient monitoring, our technology will allow us to establish a matched simulation of an individual patient's physiology. The resulting personalised bedside simulation will allow clinicians to test planned interventions and to estimate vital parameters in the patient that would otherwise be inaccessible. In addition to acting passively, the technology will proactively advise on optimised treatment strategies that are expected to improve patient outcome. The technology will scan the patient's treatment and physiological data continually, seeking potential improvements in management, and testing proposed treatment strategies by applying them to the personalised simulation and assessing outcome.Personalised optimisation of critical care treatment offers the opportunity to improve patient outcomes and reduce days spent receiving mechanical ventilation in the intensive care unit, and has the potential for enormous impact in terms of reducing patient suffering and healthcare expenditure. We will make this potential a reality by working closely with our business partner Medtronic (the world's largest standalone medical technology development company, and a leading ventilator manufacturer) and with our clinical partner Prof. Luigi Camporata, a consultant in intensive care medicine at Guy's and St Thomas' NHS Foundation Trust (one of the UK's leading centres for research on the treatment of critical illness).",2020,2021,University of Warwick,1082146.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery | Health financing",2017 +C01307,EP/P033075/1,New developments in non-reversible Markov chain Monte Carlo,"The exploration performed by a Markov chain Monte Carlo (MCMC) algorithm can be likened to the exploration of some interesting terrain. Traditional MCMC is `reversible': the simplicity of this condition has facilitated the huge number of extensions and variations on the standard MCMC algorithm that are available today; however reversibility also implies that on relatively flat terrain (and in real, high-dimensional applications only one direction is `uphill', with all other directions relatively flat), an MCMC `walker' loses their sense of direction so that their path becomes erratic and the exploration slow. By contrast, non-reversible MCMC keeps a sense of direction even over flat terrain. Current non-reversible algorithms come in two main flavours: one imagines a drone flying in a straight line above the terrain and occasionally changing direction so as to keep above the higher regions; the other inverts the terrain and imagines kicking a ball along it in a random direction. Both of these methods have great potential, but also practical problems that limit their usability. Drawing on both methods, this project will create new non-reversible algorithms which are much more efficient than standard, reversible, MCMC and can be applied across a wide variety of contexts; it will also create easy-to-use software for statistical practitioners. MCMC is used for the statistical analysis of complex data sets across a huge range of applications, from finance and fraud detection, through understanding, predicting and intervening in the spread of infectious diseases, to understanding the location of dark matter in the universe, and our work will benefit anyone analysing complex datasets in these and many other areas.",2020,2021,Lancaster University,409070.76,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Not applicable,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2017 +C01308,EP/R013756/1,The Future Vaccine Manufacturing Research Hub (Vax-Hub),"Vaccines are the most successful public health initiative of the 20th century. They save millions of lives annually, add billions to the global economy and extended life expectancy by an average of 30 years. Even so, the UN estimates that globally 6 million children each year die before their 5th birthday. While vaccines do exist to prevent these deaths, it is limitations in manufacturing capacity, technology, costs and logistics that prevent us for reaching the most vulnerable. The UK is a world leader in vaccine research and has played a significant leadership role in several public health emergencies, most notably the Swine Flu pandemic in 2009 and the recent Ebola outbreak in West Africa. While major investment has been made into early vaccine discovery - this has not been matched in the manufacturing sciences or capacity. Consequently, leading UK scientists are forced to turn overseas to commercialise their products. Therefore, this investment into The Future Vaccine Manufacturing Hub will enable our vision to make the UK the global centre for vaccine discovery, development and manufacture. We will create a vaccine manufacturing hub that brings together a world-class multidisciplinary team with decades of cumulative experience in all aspects of vaccine design and manufacturing research. This Hub will bring academia, industry and policy makers together to propose radical change in vaccine development and manufacturing technologies, such that the outputs are suitable for Low and Middle Income Countries. The vaccine manufacturing challenges faced by the industry are to (i) decrease time to market, (ii) guarantee long lasting supply - especially of older, legacy vaccine, (iii) reduce the risk of failure in moving between different vaccine types, scales of manufacture and locations, (iv) mitigating costs and (v) responding to threats and future epidemics or pandemics. This work is further complicated as there is no generic vaccine type or manufacturing approach suitable for all diseases and scenarios. Therefore this manufacturing Hub will research generic tools and technologies that are widely applicable to a range of existing and future vaccines. The work will focus on two main research themes (A) Tools and Technologies to de-risk scale-up and enable rapid response, and (B) Economic and Operational Tools for uninterrupted, low cost supply of vaccines. The first research theme seeks to create devices that can predict if a vaccine can be scaled-up for commercial manufacture before committing resources for development. It will include funds to study highly efficient purification systems, to drive costs down and use genetic tools to increase vaccine titres. Work in novel thermo-stable formulations will minimise vaccine wastage and ensure that vaccines survive the distribution chain. The second research theme will aim to demystify the economics of vaccine development and distribution and allow the identification of critical cost bottlenecks to drive research priorities. It will also assess the impact of the advances made in the first research theme to ensure that the final cost of the vaccine is suitable for the developing world. The Hub will be a boon for the UK, as this research into generic tools and technologies will be applicable for medical products intended for the UK and ensure that prices remain accessible for the NHS. It will establish the UK as the international centre for end-to-end vaccine research and manufacture. Additionally, vaccines should be considered a national security priority, as diseases do not respect international boundaries, thus this work into capacity building and rapid response is a significant advantage. The impact of this Hub will be felt internationally, as the UK reaffirms its leadership in Global Health and works to ensure that the outputs of this Hub reach the most vulnerable, especially children.",2020,2021,University College London,8549955.63,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation | Research on Capacity Strengthening",Vaccine trial design and infrastructure | Systemic/environmental components of capacity strengthening,2018 +C01309,EP/R013764/1,Future Vaccine Manufacturing Hub: Advancing the manufacture and deployment of cost effective vaccines,"Vaccine manufacturing systems have undergone evolutionary optimisation over the last 60 years, with occasional disruptions due to new technology (e.g. mammalian cell cultures replacing egg-based systems for seasonal influenza vaccine manufacture). Global vaccination programmes have been a great success but the production and distribution systems from vaccines still suffer from costs associated with producing and purifying vaccines and the need to store them between 2 and 8 degrees C. This can be a challenge in the rural parts of low and middle income countries where 24 million children do not have access to appropriate vaccinations every year. An additional challenge is the need to rapidly respond to new threats, such as the Ebola and Zika viruses, that continue to emerge. The development of a ""first responder"" strategy for the latter means that there are two different types of challenges that future vaccine manufacturing systems will have to overcome: 1. How to design a flexible modular production system, that once a new threat is identified and sequenced, can switch into manufacturing mode and produce of the order of 10,000 doses in a matter of weeks as part of localised containment strategy? 2. How to improve and optimise existing manufacturing processes and change the way vaccines are manufactured, stabilised and stored so that costs are reduced, efficiencies increased and existing and new diseases prevented effectively? Our proposed programme has been developed with LMIC partners as an integrated approach that will bring quick wins to challenge 2 while building on new developments in life sciences, immunology and process systems to bring concepts addressing challenge 1 to fruition. Examples of strategies for challenge 1 are RNA vaccines. The significant advantage of synthetic RNA vaccines is the ability to rapidly manufacture many thousands of doses within a matter of weeks. This provides a viable business model not applicable to other technologies with much longer lag phases for production (viral vectors, mammalian cell culture), whereby procurement of the vaccine can be made on a needs basis avoiding the associated costs of stockpiling vaccines for rapid deployment, monitoring their on going stability and implementing a cycle of replacement of expired stock. In addition, low infrastructure and equipment costs make it feasible to establish manufacture in low-income settings, where all required equipment has potential to be run from a generator driven electrical supply in the event of power shortage. This fits the concept of a distributed, flexible platform technology, in that once a threat is identified, the specific genetic code can be provided to the manufacturing process and the doses of the specific vaccine can be produced without delay. Additional concepts that we will explore in this category include the rapid production of yeast and bacterially expressed particles that mimic membrane expressed components of pathogenic viruses and bacteria. Examples of strategies for challenge 2 build on our work on protein stabilisation which has been shown to preserve the function of delicate protein enzymes at temperatures over 100 degrees C. We shall exploit this knowledge to develop new vaccine stabilisation and formulation platforms. These can be used in two ways: (a) to support the last few miles of delivery from centralised cold chains to patients through reformulation and (b) for direct production of thermally stable forms, i.e. vaccines that retain their activity for months despite being not being refrigerated. We believe that the best way to deliver these step changes in capability and performance is through a team-based approach that applies deep integration in two dimensions: between UK and LMIC partners to ensure that all the LMIC considerations are ""baked in"" from the start and between different disciplines accounting for the different expertise that will be required to meet the challenges.",2020,2021,Imperial College London,12205668.39,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2017 +C01311,EP/R018561/1,New Approaches to Bayesian Data Science: Tackling Challenges from the Health Sciences,"The health sciences have seen an explosion in the amount of data collected at both individual and population levels. This data can be varied, including genetic information, health records, data on activity levels obtained from wearable devices, and image data from scans. There is huge potential for improved diagnoses, timely interventions and more effective treatments if we can fully extract understanding from this data. Example applications included real-time monitoring of patients, developing personalised treatment, or real-time monitoring and decision-making for epidemics. However the data science challenges in extracting these insights are vast. Features of these challenges include the need to make inferences about and decisions for individuals from within a population, and the need to synthesise information from disparate data sources and data types. Whilst we have substantial data collected at a population level, the amount of information on any given individual may be still be limited. Appropriately quantifying uncertainty is crucial for making decisions, with the optimal decision often being driven by the probability of relatively rare events (e.g. extreme reaction to a drug). We need model-based approaches to data science that can leverage scientific understanding, but we need the statistical analyses to be robust to unavoidable inadequacies of these models. Underpinning many of these applications is the requirement to develop new understanding, and this differs from a focus on making predictions that it is most common among current statistical or machine learning methods. Bayesian data science provides a natural framework for tackling these challenges. Bayesian methods are model-based, can appropriately quantify and propagate uncertainty, and through hierarchical models are able to use population-level information when making inferences about individuals. Repeated application of Bayes theorem gives a natural paradigm for synthesizing information across multiple data sources. However, current Bayesian data science methods are not feasible for many modern, big-data, applications in the health sciences. Bayesian methods require integrating over uncertainty. Such high-dimensional integration carries a substantial computational overhead when compared to alternative, often optimization-based, data science methods. So while the motivation for Bayesian analysis is clear, this computational overhead means that, currently, implementing Bayesian approaches is often not feasible. This programme of research will develop the new approaches to Bayesian data science that are needed both within the health sciences and more widely. It builds on recent breakthroughs in Monte Carlo integration methods that show great promise for being efficient for large data; and on new paradigms for Bayesian-like updates that are suitable for complex models and which focus modelling effort just on the aspects of these models that are most important. It will address key research challenges in the health sciences -- directly developing new insights and understanding for these.",2020,2023,Lancaster University,3622888.05,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Not applicable,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2018 +C01312,EP/R023204/1,"Geometry as a key to the virosphere: Unmasking the fundamental roles of geometry in virus structure, evolution and pathology","Society faces major challenges from viral diseases. The recent Zika and Ebola outbreaks are only two examples of the devastating impact of viral illnesses on human health, and viral pathogens infecting agriculturally important livestock and plants simultaneously reduce food production and inflict great annual financial losses worldwide. Viruses, however, also have positive impacts on health and ecology. They balance and stabilise our gut microbiome, preventing serious illnesses such as certain autoimmune diseases, and influence our climate owing to their roles in carbon cycling in the oceans. It is therefore paramount to better understand virus structure and function across the entire virosphere in order to control, and even take advantage of, viruses in medicine and biotechnology. I have demonstrated previously that mathematical approaches developed in tandem with experimentalists are drivers of discovery of functionally crucial structural viral features, revealing their novel functional roles in viral life cycles, and enabling their exploitation in therapy and biotechnology. Previously developed mathematical approaches were geared towards a specific major sub-group of the virosphere. In this research programme, I will both broaden and deepen the development of novel mathematical techniques. Working in close collaboration with leading experimental groups, at a larger scale, I will identify functionally important geometric viral features in a number of major groups of viruses. This will include: geometric strand assortment in multipartite viruses, such as the major agricultural pathogen Bluetongue virus; the assembly of retroviruses like HIV, with applications to the construction of virus-like particles from viral components as vectors for gene editing and therapy; and the structure and evolution of viruses important for the gut microbiome and marine ecology. By linking structural features with their functions, I will address open problems regarding drivers of evolution in one of the simplest yet most important groups of biological entities. This approach will unmask evolutionarily conserved functional features that can be used as novel targets in anti-viral therapy, for the development of novel safer vaccines or repurposed in bionanotechnology.",2020,2023,University of York,1326671.66,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Pre-clinical studies",2018 +C01313,EP/R00529X/1,i-sense: EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (i-sense COVID-19: Harnessing digital and diagnostic technologies for COVID-19),Additional funding for the I-sense IRC to address the COVID-19 Pandemic. Vision: To harness the multidisciplinary expertise within the i-sense EPSRC IRC track and test Flagship programmes to address the key challenges associated with the COVID-19 pandemic; namely early identification of infection in the community through online data sources and point-of-care diagnostic tests (PoCT) linked to national health systems. We request £500K of emergency funding initially to seed a 12 month 'Plus Award' focused on urgent national needs,2020,2022,University College London,5276860.74,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2018 +C01315,EP/S032002/1,Decarbon8 Network,The Decarbon8 network have been awarded an additional £75k to investigate the environmental impact of as a result of COVID-19. This looks at the challenge from an energy and transport perspective since there will be significant drops in greenhouse gases' emissions during this period.,2020,-99,University of Leeds,1637457.27,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01316,NS/C000001/1,Nanoparticle dispersions for pulmonary delivery of antiviral drugs to combat COVID-19,Limited ventilator availability is currently a global issue. This project aims to provide an alternative to ventilation by building upon ongoing solid drug nanoparticle formulation research of antivirals to develop therapeutic nebulised medicine options for COVID-19 treatment,2020,-99,University of Liverpool,20040.59,Other,Not applicable,Unspecified,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C01317,NS/C000002/1,Anti-viral surfaces and materials,Existing disposable anti-viral surfaces - that can be readily replaced for example as a new patient moves into a bay - will be optimised and translated to acquire anti-COVID-19 properties.,2020,-99,University of Liverpool,20040.59,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings, +C01318,NS/C000003/1,Plasma-activated aerosols for on-demand ambulance sanitisation,"This work addresses an urgent need to increase the efficiency of ambulance cleaning procedures by using aerosolised plasma activated water for rapid ambulance sanitisation. Researchers will exploit the advantageous characteristics of plasma activated water to develop a low cost handheld sanitisation device, enabling crews to rapidly clean their own ambulance without large quantities of liquid disinfectant or returning the ambulance to a cleaning centre.",2020,-99,University of Liverpool,20040.59,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C01319,NS/C000004/1,AI-based medical image analyses to speed up accurate diagnosis of COVID-19,New artificial intelligence techniques will be developed for fast and accurate diagnosis of COVID-19 using automated interpretation of CT and X-ray images. The resulting software tools will be made publicly available free of charge after initial internal validations.,2020,-99,University of Liverpool,20040.59,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C01320,NS/C000005/1,Effect of diagnostic uncertainty in mass testing on the spread of COVID-19,This project aims to support clinical decision making through a robust estimation of the efficacy of the UK testing strategies during the 'containment phase'. A second phase will develop analyses of a variety of testing strategies applicable at community and national level.,2020,-99,University of Liverpool,20040.59,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Impact/ effectiveness of control measures, +C01321,NS/C000006/1,Capitalising on big hypotheses for significantly better decision support for COVID-19,"This project will empower COVID-19 decision makers by developing a data fusion system to bring together key expertise from disparate sources to improve the holistic understanding of COVID-19. A prototype system could provide, for example, daily forecasts of ICU bed demands for each NHS region in the UK to help decision makers agree appropriate social distancing measures.",2020,-99,University of Liverpool,20040.59,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C01322,EP/V010948/1,COVID-19 - Exploration of potential therapeutics against underexplored targets.,"The genome of SARS CoV-2 encodes proteins which perform various functions essential for the replication of the virus. By exploiting our knowledge of the 3D structures of these proteins we can identify and/or design small molecules (i.e. drugs) that bind to viral proteins to prevent them from performing their normal function. COVID-19 research groups worldwide been determining 3D structures of proteins encoded within the viral genome. The focus has been on high-profile target proteins of Cov-2, including the protease, spike protein and helicases. Perhaps surprisingly, less effort is being directed towards other promising targets for which there is structural information. We focus on two underexplored proteins, NSP9 (involved in RNA processing) and E protein (a viroporin). NSP9 helps the virus to replicate its genome. By identifying a compound that binds to NSP9, we would have a potential drug to halt viral replication in infected cells. E protein is a viroporin, forming channels in infected cell and viral membranes. Molecules which 'plug' the channel (""channel blockers"") are potential anti-viral drugs. For target proteins, we will combine advanced molecular simulations in Oxford with AI-driven identification of potential compounds by IBM to enable and accelerate identification of compounds which could be repurposed as candidate anti-viral drugs. The IBM generative AI method has already been successful in identifying new antimicrobials that have since been experimentally validated. The work here will be undertaken as part of a long-standing collaboration between Oxford and IBM and the strong relationship will ensure delivery of this highly collaborative effort.",2020,2021,University of Oxford,192769.06,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C01323,EP/R00529X/1,i-sense: EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (i-sense COVID-19: Harnessing digital and diagnostic technologies for COVID-19),Additional funding for the I-sense IRC to address the COVID-19 Pandemic. To harness the multidisciplinary expertise within the i-sense EPSRC IRC track and test Flagship programmes to address the key challenges associated with the COVID-19 pandemic; namely early identification of infection in the community through online data sources and point-of-care diagnostic tests (PoCT) linked to national health systems.,2020,-99,University College London,490800,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics, +C01324,EP/S025987/1,Next Generation Sensing for Human in vivo Pharmacology - Accelerating Drug Development in Inflammatory Diseases in collaboration with GSK,"Led by the University of Edinburgh, Centre for Inflammation Research, the team wish to rapidly instigate, operationalise and deliver a cross-sector, multidisciplinary programme to expedite repurposing of promising pharmaceutical assets with prior use in man for lead prioritisation and evaluation in experimental clinical trials with readiness for global access. The key intervention is to prevent the lung damage in patients with COVID-19 that leads to respiratory failure, therefore reducing the need for MV and saving lives. As part of this strategy, an enabling technology is currently being developed within this EPSRC HIPS award. The goal of the original HIPS grant in collaboration with GSK was to further develop a cutting-edge point-of-care technology platform which would help drug developers, patients, doctors and healthcare workers throughout the world. This platform, KronoScan , was initially intended to be used as an ultra-sensitive microscopic imaging tool in the evaluation of drug action, with a particular focus on drug development for diseases which are characterised by infectious and inflammatory pathway-mediated tissue injury. This additional funding is to urgently expedite the translation/evaluation and use of Kronoscan in the setting of experimental medicine to evaluate novel therapies targeting fulminant respiratory failure due to ARDS.",2020,-99,University of Edinburgh,481798.73,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments", +C01325,EP/S001123/1,UKRI Innovation Fellowship: Next Generation Endoscopes. Multifunctional endoscopic pharmaceutical treatments for COVID-19,"As part of these COVID-19 related activities the applicant is seeking urgent funding to rapidly push and translate their endoscopic device (Panoptes) into COVID-19 focussed clinical studies. It will be used in conjunction with optical imaging platforms developed at the University of Edinburgh. Together these will enable them to (i) understand how COVID-19 is causing lung damage and respiratory failure and (ii) rapidly screen and monitor promising pharmaceutical assets which are either repurposed or at an advanced stage with feasibility studies in patients. They are specifically seeking funds to expedite the Panoptes device through regulatory approval and improve, streamline and upscale the Panoptes manufacturing process. This will enable them to produce devices for clinical use and to carry out research using direct clinical feedback from initial interventions to further develop the Panoptes platform thus contributing a vital role in the research of the broader consortium into COVID-19.",2020,-99,University of Bath,387803.17,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C01326,EP/S032002/1,Decarbon8 Network,"This proposal for emergency funding from UKRI relates to one of the most critically impacted sectors, transport and mobility. The aims of the proposal are to: i) Capture a new set of data assets during the period of disruption and recovery from the emergency ii) Provide early insights from this evidence to inform the policy response in relation to short and longer term mobility adaptation iii) Maximise the benefits of existing UKRI investments to leverage knowledge, pool expertise and tap in to existing data assets",2020,-99,University of Leeds,92025,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C01328,EP/R024804/1,New Branched Polymer Excipients and Emulsions for Enhanced Drug Delivery,"This translational science research aims to build upon ongoing work across University of Liverpool and Liverpool School of Tropical medicine. The work aims to accelerate preclinical validation of drugs for Covid-19 treatment and/or prevention. To maximise healthcare impact, the work seeks to establish three direct outputs, namely; 1) Selection of candidates based on in vitro anti-SARS-CoV-2 activity, 2) Demonstration of In vivo pharmacokinetics and distribution supporting treatment and prevention applications, and 3) Demonstration of in vivo performance in mice infected with SARS-CoV-2. We expect the research to provide evidence-based candidates for evaluation in human clinical trials. We will also undertake additional evaluations for low-middle income settings, focussing on scalability and affordability in sub-Saharan Africa and preferring orally delivered medications, with little or no laboratory monitoring.",2020,-99,University of Liverpool,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies, +C01329,EP/N010523/1,Balancing the impact of City Infrastructure Engineering on Natural Systems using Robots,"For the foreseeable future, the UK is at risk from COVID resurgence. Upon the relaxation of lockdown, public transport and transport hubs will become key hotspots where the virus has a significantly enhanced likelihood of transmission. Confidence in the cleanliness of our mass transport systems will be essential to reopening the country; without this, people will shun public transport and a large increase in private vehicle traffic will result, with corresponding impacts on carbon, particulate and nitrogen pollution. The UK will need to achieve unprecedented levels of cleanliness on its mass transport systems and the UK robotic community can provide novel technology to enable this. Some countries (e.g. Singapore) already use basic robotic technology to clean trains or to spray streets with disinfectant. Building on our world-class expertise in novel configurations of drones and ground vehicles, we will research and develop robotic systems such as autonomous drones with spray and manipulation capability to contact and disinfect structures. We have already demonstrated autonomous spraying robots and drones with manipulators as part of the international MBZIRC challenge in the UAE this year, and have demonstrated ground robots with wheels and legs equipped for firefighting. Time is critical; we need to adapt the technology urgently to reboot transport systems.",2020,-99,University of Leeds,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C01330,EP/P023312/1,"Hospital Environment Control, Optimisation and Infection Risk Assessment (HECOIRA)",The hospital sampling work will provide valuable data to understand the evolution of environmental contamination in a hospital environment. Published studies to date have taken snapshot samples but give little information of how viral load in the environment changes with space and time. The data is valuable to inform infection control guidelines and to provide data to quantify the transmission of SARS-COV-2 in the environment. There will be an immediate benefit for Leeds Teaching Hospitals NHS Trust as they will have knowledge on the prevalence of SARS-CoV-2 in their wards. Publication in an international journal will make this available for global researchers.,2020,-99,University of Leeds,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings, +C01331,EP/N010221/1,Managing Air for Greener Inner Cities,"Estimates of personal exposure, critical to determine safe procedures in hospitals and in public places (e.g. shops and restaurants), are needed now and post-lockdown. It is also essential that ventilation strategies, the effectiveness of PPE and other containment measures (e.g. curtains, air locks etc.) are evaluated to avoid unnecessary spread of the infection. WHO guidelines suggest ventilation rates in hospitals should be 160 l/s/person. This is based on inefficient modes of ventilation and is not achievable in most cases. The MAGIC team has interdisciplinary expertise that can recommend alternative ventilation strategies that are urgently needed. This work will also provide better information and advice if there were to be subsequent waves in the future.",2020,2021,University of Cambridge,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2015 +C01332,EP/P011330/1,Efficient modelling and validation of cryptic protein binding sites for drug discovery,"To respond to the COVID19 emergency I have put together a project involving two colleagues at the School of Chemistry (Prof Hulme, Prof Barlow) of the University of Edinburgh to pursue a project entitled ''Fluorescent peptide binders of the SARS-CoV-2 Spike protein to accelerate development of COVID-19 diagnostics and drug therapies''. This project will be pursued in collaboration with colleagues in the School of Biological Sciences (Prof Auer) and the College of Medicine (Prof Dhaliwal). We wish to develop fluorescent probes to tag live SARS-CoV-2 virions that could be used for medical imaging and rapid point-of-care diagnostic applications. There is a real urgency to pursue this activity now. The Queens Medical Research Institute at the University of Edinburgh has formed the STOPCOVID research hub to exploit unique strengths in optical imaging technologies to monitor COVID-19 patient's lungs with an array of optical sensor probes. However, to date a fluorescent probe that selectively tags SARS-CoV-2 virions does not exist. Such optical probe would be extremely useful to assay drugs for their ability to prevent fusion of patient derived viral strains with host cells. It could also form the basis of cheap point-of-care biosensor technology to detect live viruses on surfaces. This could find immediate applications in decontamination of PPEs and clinical facilities, or as a diagnostic technology in LMIC countries that lack ready access to facilities with RT-PCR equipment and trained technical staff. Affordable and easily deployable testing worldwide will be essential to prevent future outbreaks from getting out of control.",2020,-99,University of Edinburgh,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies, +C01333,EP/V018450/1,COVID-19: Fast multi-shot epidemic interventions for post lockdown Covid-19 mitigation: Open-loop mitigation strategies,"The objective of this 4-month SPRINT is to design and validate new exit-strategies from the current lockdown policy that actively suppress COVID-19, while allowing significant economic activity. Currently proposed exit-strategies suggest that intermittent lockdowns, in addition to contact tracing, masking, and other measures, may be necessary until an effective vaccine is found. Most of the these propose using data-driven feedback signals, such as hospital admissions, to initiate lockdowns, with a key design consideration being the capacity of the healthcare system. The difficulty with this approach is timing. Intervene too early, and one simply shifts the peak of ill people to a later date, whereas too late an intervention will not limit the peak of infections. The issue of timing is exacerbated by the virus having up to a 14-day incubation period and an initial exponential growth rate. Thus, the problem of observing the true state of the epidemic, in the face of exponential growth, makes the effectiveness of any data-driven feedback policy extremely sensitive to the timing of intervention. From a classical perspective, controlling locally unstable systems, as this is, with time-varying time-delays, is known to be a frontier problem in control engineering. Our suggestion is to circumvent this difficulty by developing periodic open-loop lockdown strategies over short timescales. Such policies, will help suppressing the virus and allow predictable periodic periods of lockdown, thereby facilitating economic activity. The policies will be validated on advanced, realistic epidemiological mathematical models and data, and will be developed for national and international compartmental scenarios.",2020,2020,Imperial College London,177915,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Policy research and interventions,2020 +C01334,EP/V01479X/1,Meeting the UK demand for COVID19/SARS-CoV-2 vaccines via integrated manufacturing and supply chain optimisation,"We shall deliver a blueprint for simultaneously ramping up production and ensuring uninterrupted delivery of SARS-CoV-2 vaccines in the UK to manage and prevent subsequent waves of the pandemic. We shall assist decision-making of manufacturers, governments and stakeholders during SARS-CoV-2 vaccine manufacture and distribution to ensure increased vaccine availability particularly during early stages of manufacturing. The proposed work will consider the UK population in its entirety from the outset with respect to both the population stratification strategy, based on health, disease exposure and socio-environmental risks, and vaccine distribution networks throughout the country including remote communities. Through our involvement in the vaccine hubs funded by the Department of Health (EP/R013764/1 and EP/R013756/1), we have developed world-leading capabilities in vaccine manufacturing and supply chain modelling and optimisation. Early access to the vaccine development efforts by the Jenner Institute in Oxford and the Shattock group at Imperial, has enabled us to develop accurate manufacturing models that will underpin the proposed research. We have access to a remarkable network of key UK and international vaccine stakeholders (CEPI, IAVI), manufacturers (GSK), BIA (via CPI) and governmental bodies, such as the Department of Health who will provide feedback and datasets.",2020,2021,Imperial College London,546015,Other,Not applicable,Not Applicable,Rural Population/Setting | Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2021 +C01335,EP/V015087/1,Synthesis of Targeted Antiviral Nucleosides,"The emergence and rapid spread of the SARS-Cov-2 virus is a major health threat to the UK and to the rest of the world. Accordingly, major research effort has been made to tackle the virus, with current focus on the development of vaccines and the repurposing of existing antiviral therapies not originally designed for SARS-Cov-2. Unfortunately, it is entirely feasible that a vaccine cannot be developed in time, and that existing therapeutics are ineffective. Therefore, novel antivirals targeted to SARS-Cov-2 are urgently required. In order to meet the critical need for new antivirals with targeted activity, this project will enable the rapid generation of structures primed for testing against the viral replication machinery. Whilst a viable mechanism to shut down viral replication is known, the identification of a molecule able to achieve this in the clinic has not been successful. In this project, we are targeting motifs whose biological activity as non-natural nucleoside analogues is known, but currently underexplored as they are difficult to make. They have high similarity to molecules currently being tested against SARS-Cov-2, Remdesivir, Galidesivir, and EIDD-2801, but contain unique motifs that may overcome the limitations of these current therapies. The exploration of these molecules - their biological testing and accompanying structural studies - will teach us more about the mode of action of these antiviral therapies, allow the design of more active species, and lead the way for the discovery of a new, effective treatment.",2020,2021,University of Oxford,548626.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C01336,ST/V00221X/1,Rapid Assistance in Modelling the Pandemic (RAMP - Edinburgh central admin),"Since the pandemic began, many thousands of researchers have had their work interrupted, with no access to laboratory equipment or travel. They stand willing and to contribute to COVID modelling effort. RAMP addresses the need to coordinate and focus the efforts across the UK. Computer modelling is perhaps unique as an area where capacity is actually enhanced by the lockdown, although we will continue to coordinate projects with new or repurposed funding once restrictions are relaxed until the crisis is truly over. The unique situation of lockdown and unprecidented importance of COVID has meant that the generation of new knowledge has advanced apace without direct funding. Thousands of apparently COViD related preprints have appeared across medarXiV, arXiV and other preprint servers, and in the inboxes of all prominent scientists in the field. However this body of work is unfocussed, hugely repetitive and often lacks the specificity to deal with the details of the actual crisis we face. The central aim of this project is to provide focus to this effort, and facilitate the knowledge transfer to policy-making. In addition, we are and will continue to act as a channel for addressing policy questions to the community and escalating promising avenues of work to decision-makers, with co-membership of RAMP and the government's SPI-M and SAGE committees. RAMP provides a mechanism by which useful work which does not require direct funding can get underway immediately.",2020,2021,University of Edinburgh,270530.19,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C01337,971613,Serological Vaccine Standards for Emerging Diseases,"The development of safe, effective and economically affordable vaccines against Emerging Diseases, such as Ebola and Zika, would provide powerful tools not only to prevent re-emergence of these diseases in countries where they are endemic, but also enable swift and effective control of outbreaks initiated by infected returning travellers.  However, these infectious agents can only be handled under high levels of bio-security, making the cost of research on these agents prohibitive for most commercial organisations.  The availability of established standards and reference materials accelerates the development of licenced vaccines.  Where there is robust evidence that convalescent serum (ie serum obtained from someone who has recovered from an infectious disease) protects against reinfection, then the preparation and distribution of serum standards that have been demonstrated to confer protection against infection is hugely beneficial.  These serum standards facilitate pre-clinical and early clinical development and selection of the most promising experimental vaccine without the need for expensive studies under bio-containment, as the serum standard provides as in vitro reference marker for serological protection. NIBSC is the global leader in the development of World Health Organisation (WHO) established International Standards and reference materials for biological medicines such as vaccines.  At the request of the WHO, NIBSC is undertaking a programme to develop and establish sero-diagnostic reference materials for the WHO's List of Priority Pathogens,that heavily overlaps with the UK Vaccine Network Priority Emerging Diseases.   NIBSC has prepared an International Standard for anti-Ebola virus antibodies that was established by the WHO's Expert Committee for Biological Standardisation in October 2017.  An anti-Zika virus antibody standard will be reviewed in October 2018 as well as a preliminary report about an anti-MERS-CoV antibody material. Whilst these candidate materials have been through detailed in vitro analyses in international collaborative studies, without additional competitively awarded funding from InnovateUK, it would not have been possible to establish that the serological reference materials contained specific antibodies capable of preventing infection or disease in in vivo model systems.  They are now established as serological vaccine standards and available globally. This previous Innovate UK funding, (for 1 year) enabled NIBSC to collaborate with Dstl and PHE laboratories at Porton Down.   Their high level bio-containment facilities allowed these critical protection studies to be performed and demonstrated that serological reference materials against Ebola, Zika and MersCoV could protect against these lethal diseases.  Having established an effective collaboration between the 3 centres, NIBSC is now seeking a further 2 years funding to build on this momentum, utilising this PLATFORM TECHNOLOGY to prepare a further 9 candidate sero-diagnostic reference preparations, one each for the remaining UK Vaccine Network Priority Emerging Diseases, and establish whether these materials can protect in appropriate in vivo model systems.  If materials protect, then they add to the list of serological vaccine standards and thus accelerate vaccine development against Chikungunya, CCHF, Marburg, Lassa Fever, Nipah, Hanta, Rift Valley Fever viruses and bacterial infections Q Fever and Plague.",2020,2022,National Institute for Biological Standards and Controls,2452838.03,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Flaviviridae,,,,,,,,,Lassa fever | Rift Valley Fever | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Marburg virus disease | Zika virus disease | Nipah and henipaviral disease | Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2018 +C01338,Support funding,Innovation and Growth Advisory Services,,2020,-99,N/A,47853000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,Unspecified,,,,,,,, +C01475,62121,Emergency Construction for COVID19: A Voice-Activated BIM System for Boosting Productivity for On-Site ASSEMBLAGE and DISASSEMBLY,"BACKGROUND AND PROBLEM STATEMENT: According to WHO (2020), the outbreak of the Coronavirus disease (COVID-19) is a global pandemic that has recorded more than 40million cases, resulting in more than 1.13million deaths. Although more than 28million people have recovered, evidence suggests that there may be a possibility of relapse or reinfection (Independent, 2020). As UK activities resumes back to normal, there is an imperative need for plethora of sectors, particularly the construction industry to Build-Back-Better from COVID-19 by significantly improving Health & Safety and Productivity which have bedevilled the industry (Ajayi et al., 2019). According to PBC Today (2019), Building Information Modelling (BIM) has been unanimously agreed to being central to boosting productivity for on-site assemblage and disassembly. However, evidence suggests that to further improve on-site construction productivity through BIM, its usability needs to be modernised (Goucher and Thurairajah, 2012). At present, BIM provides Conventional Web and Mobile interfaces for interactions that require tremendous time and efforts to master their usage. In this trying time where time is of the essence and workers are fearful about their susceptibility to COVID-19, the last thing on-site assemblage and disassembly workers need is to spend needless time searching BIM models while performing their routine tasks. It is on this premise that Clytell (UK) Limited has spent the last 14 months developing a VOICE-Activated BIM system for boosting productivity for on-site assemblage and disassembly (VOICE-BIM). THE INTERVENTION OF VOICE-BIM AND ITS BENEFIT: In light of this COVID-19 pandemic, VOICE-BIM will significantly improve productivity by enabling users to quickly interact with BIM Models using their voice. This will aid on-site assemblage and disassembly. Also, VOICE-BIM will potentially reduce the spread of COVID-19 amongst on-site workers as the amount of time they touch on-site hardware to access BIM tools will be significantly reduced.",2020,2021,CLYTELL (UK) LIMITED,91775.92,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01742,01KI2047,African Network vor Coronavirus Surveillance,"discovery - Compared to other regions of the world, acute respiratory infections in sub-Saharan Africa cause a disproportionately high burden of illness and death. The aim of this project is to combat transnational acute respiratory diseases, which can be attributed to the current outbreak of COVID-19, in sub-Saharan Africa. For this purpose, the routine molecular biological detection of SARS-CoV-2 is established in central laboratories in Burkina Faso, the Republic of Côte d'Ivoire, the Democratic Republic of the Congo and South Africa. The rapid introduction of corresponding tests is made possible by a close connection to the BMBF-funded African Network for the Detection, Epidemiology and Management of common Infectious Agents (ANDEMIA), which has been running successfully since 2017 and which uses hospital-based monitoring and recording to detect acute respiratory and gastrointestinal diseases and tries to combat acute fever of unknown origin and the spread of multi-resistant pathogens in sub-Saharan Africa. With this project, the detection of SARS-CoV-2 in patients with acute respiratory symptoms is now linked to the acquisition by ANDEMIA. This lays the foundation for the further outbreak and risk areas in Africa to be recorded.",2020,2021,Robert Koch Institute - RKI,55870,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Africa,,,,Germany,Burkina Faso | South Africa | Cote d'Ivoire | Congo (DRC),Epidemiological studies,Disease transmission dynamics,2020 +C01743,01KI20270,ARRay- ACE-2 Rezeptor-basierte Reagenzien als Werkzeuge zur Qualitätsbewertung von Immunoassayreagenzien und zur Entwicklung von Assays zur qualitativen Bewertung von SARS-CoV-2-spezifischen Immunantworten,"discovery - Due to the currently high number of diagnostic tests against SARS-CoV-2 being developed, test materials, the so-called validation reagents, represent a bottleneck for the development of diagnostics. The aim of the project is to develop validation reagents for these tests that are simple and in large quantities can be produced. As such a validation reagent, the human protein ACE2 in various variants is to be produced in plant cells and tested for its suitability. If produced successfully in plant cells, the reagent could be produced simply and in large quantities if successful.",2020,2020,"Fraunhofer-Gesellschaft, München",55460.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01744,01KI20161,Analysis of cellular immune disturbances in COVID-19 for therapeutic stratification and prediction of long-term immunity.,"discovery - This research project aims at expanding knowledge on human primary and secondary antigen-specific B lineage responses to a novel pathogen - severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). We will study the characteristics of host-SARS-CoV-2 interaction with B lineage adaptive immunity including induction of anergy among different clinical courses of Corona Virus disease 2019 (COVID-19). The study will provide mechanistic evidence for novel treatment strategies currently adapted from rheumatology by comparing the immune response by COVID-19 infected individuals with those known from rheumatologic patients. We will further investigate long-term protective immunity after SARS-CoV-2 infection by analyzing serological and ""steady state"" antigen-specific B cells in the blood and bone marrow.",2020,2021,Charité-Universitätsmedizin Berlin,268958.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C01745,01KI20184,Rapid testing for CoV-2 RNA in swabs,"clinical trial - Rapid and extensive testing of both personnel and patients is crucial for proper management SARS-CoV-2 infections and decision-making in times of the current pandemic outbreak. However, point-of-care (POC) testing in emergency units or outpatient clinics is not possible yet at a larger scale using established PCR-based methods. Therefore, we tested two PCR-independent methods to detect viral RNA from primary material (swabs) circumventing the need of RNA preparation. Firstly, SHERLOCK, developed by Feng Zhang at MIT(1), uses Recombinase Polymerase Amplification (RPA) combined with Cas13a-dependent detection of RNA as a second step followed by a lateral-flow assay on a test strip. As a simple alternative, loop-mediated amplification (LAMP) only requires one incubation step with detection based either on a colorimetric assay or lateral flow strips. SHERLOCK and LAMP can be performed in 60 or 30 minutes, respectively. Based on our preliminary data, we can show that both methods work on isolated viral RNA as well as on direct material from pharyngeal swabs - a crucial pre-requisite for point-of-care testing. However, both approaches still lack sensitivity as compared to standard qPCR testing. In this proposal we aim to (1) improve and combine aspects of both SHERLOCK and LAMP to develop an easy and fast diagnostic method allowing for viral RNA detection without RNA isolation at a sensitivity comparable to qPCR and (2) to test these approaches in the setting of an emergency room.",2020,2021,Uniklinik Köln,471635.77,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01746,01KI20147,Identifizierung zellulärer Barrieren für SARS-CoV-2 auf Proteinebene mittels Y2,"discovery - The aim of the project is to identify possible interactions of SARS-CoV-2 proteins with proteins from human cells using an established in-vitro test system (Yeast Two Hybrid Screen, abbreviated to Y2H). The expected results can contribute to understanding the biology of the virus and e.g. B. Provide clues to the mechanisms of virus replication and virus entry into the host cells.",2020,2021,Ludwig-Maximilians-Universität München,67044,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C01747,01KI2040,Development of neutralizing monoclonal antibodics against the 'spike' protein of SARS-CoV-2,"discovery - We engineer extracellular vesicles (eEVs) as antigen carriers to encompass complex membrane proteins in their correct conformation. Conformational authenticity of functional antigenic domains determines the quality of immune responses. Thus, when injected into animals such eEVs can give rise to functional antibodies with superb affinity and avidity. Here, we propose to use eEVs for the systematic generation of a panel of neutralizing antibodies directed against the surface 'spike' glycoprotein of SARS-CoV-2, which is considered central to the entry and fusion of this virus with all its target cells. Using the eEV approach, we also developed a virus-free platform technology that will support the functional screening of SARS-CoV-2 neutralizing antibodies. With this novel assay we will functionally validate the different classes of antibodies obtained from immunizations with eEVs, screen for distinct neutralizing antibodies, characterize them, and humanize and express the most promising clinical candidate in CHO cells for its further preclinical evaluation with a drug target profile to prevent or curb COVID-19 infection.",2020,2021,Helmholtz Zentrum München,206779.34,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C01748,01KI20197,Identification of genetic host susceptibility in COVID-19 patients,"epidemiological study - The COVID-19 epidemic situation needs little introduction and represent a global world-wide emergency. Disease behavior is variable, with the majority of patients experiencing only mild symptoms or no symptoms at all. Some patients develop severe pulmonary affection, with aggressive and extensive inflammatory destruction of lung parenchyma and associated systemic inflammatory response syndrome (SIRS) and superinfections, driving large fractions of the COVID-19 related mortality. What exactly drives this development of severe lung disease remains unknown, but old age, smoking, obesity, diabetes and other co-morbidities increase the risk. Variation in virus genetics and patient immunology are also likely involved. As to the latter, we hypothesize that host genetics may play a role in determining development of severe lung disease in COVID-19 infection. We here aim to address the following research questions: (1) Are there genetic signatures suggesting which biological mechanisms are involved that may suggest relevant therapeutic approaches? (2) Can we predict those at risk (or those with very low risk)? (3) Are specific human leukocyte antigen (HLA) alleles/haplotypes associated with COVID19 disease? (4) Are blood groups of relevance in (a) the infection process and (b) in disease severity? Until today, no well-powered genetic analysis has been performed. To this end, we have collected 5,000 blood samples from some of the most strongest affected regions in Europe, including a significant fraction of severe COVID19 patients from intensive care units.",2020,2020,"Christian-Albrechts-University of Kiel (CAU), University Hospital Schleswig-Holstein (UKSH)",320809.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C01749,01KI20102,Prediction of SARS-CoV-2 infection dynamics and impact of policy by modeling individual decisions of the general population,"social sciences - The current SARS-CoV-2 pandemic leads to a worldwide threat of collapsing health care systems and large numbers of casualties. This necessitates a swift but appropriate response in terms of non-pharmacological interventions to prevent and control the infection. Currently, measures to restrict social contacts are the most important means of limiting the spread of the virus. These measures have economic, psychosocial and other detrimental consequences and need to be limited to the extent and duration that is absolutely necessary. Here, we propose a model that allows to estimate a projected effect of measures based on simulating the impact on individual persons and their behavior in a given environment, going beyond the current state of the art in epidemiologic models. A central improvement over conventional models is the inclusion of a fuzzy logic-based description of the decisions individuals take under the influence of restrictive measures, media reporting, and public communication of policy. By developing this model into a tool including a graphical user interface and parameterizing it based on local data, we provide an accessible way to simulate the impact of policy decisions and inform and guide political and administrative decision processes.",2020,2021,"Helmholtz Zentrum für Infektionsforschung, Braunschweig",229335.32,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Policy research and interventions,2020 +C01750,01KI20393,Untersuchungen von molekularen SARS-CoV-2-Wirt-Interaktionen mit gezielten Knockouts und Pulldowns,"discovery - This is a basic scientific research project on SARS-CoV-2. The aim of the project is to investigate in detail the mutual influences between the viruses and the metabolism of human host cells in a SARS-CoV-2 infection. Preliminary work has already identified certain ribonucleic acids (RNA) in the host cells, the expression of which is changed in the case of a SARS-CoV-2 infection. In the non-infected cell culture, this RNA should now be switched off (knockout) and the effects of an infection of the cells with the virus examined. Ultimately, possible new targets for pharmaceutical interventions against SARS-CoV-2 are to be found.",2020,2021,Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC),90173.89,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C01751,01KI2054A,Instant identification of biomarkers of COVID 19 by applying AI on structured reporting of Chest CT integrating clinical information,"clinical trial - Current evidence suggests that chest CT imaging may be an extremely valuable tool in the diagnosis, epidemiology, and therapy response control of COVID-19 cases. It offers high sensitivity, short turnaround times and wide availability, and may thus complement RT-PCR tests, especially in situations of unclear clinical presentation, such as a negative RT-PCR despite strong anamnestic evidence for COVID-19. More importantly, it may offer opportunities to directly assess the stage of progression of the disease as observed directly from the affected lung tissue, and may thus be a method of choice for therapy response assessment in upcoming trials of new therapeutic agents. However, in order to develop it into a suitable tool for these purposes, a reproducible, standardized, and quantitative approach to image diagnostics is required. This proposal aims to develop such a standardized diagnostic and staging procedure for COVID-19 cases, using an AI-supported approach to select clinical attributes that serve as optimal predictors of the presence and stage of the disease.",2020,2020,"University Heidelberg, Mint Medical GmbH, Deutsches Krebsforschungszentrum (DKFZ)",96653.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C01752,01KI2054B,Instant identification of biomarkers of COVID 19 by applying AI on structured reporting of Chest CT integrating clinical information,"clinical trial - Current evidence suggests that chest CT imaging may be an extremely valuable tool in the diagnosis, epidemiology, and therapy response control of COVID-19 cases. It offers high sensitivity, short turnaround times and wide availability, and may thus complement RT-PCR tests, especially in situations of unclear clinical presentation, such as a negative RT-PCR despite strong anamnestic evidence for COVID-19. More importantly, it may offer opportunities to directly assess the stage of progression of the disease as observed directly from the affected lung tissue, and may thus be a method of choice for therapy response assessment in upcoming trials of new therapeutic agents. However, in order to develop it into a suitable tool for these purposes, a reproducible, standardized, and quantitative approach to image diagnostics is required. This proposal aims to develop such a standardized diagnostic and staging procedure for COVID-19 cases, using an AI-supported approach to select clinical attributes that serve as optimal predictors of the presence and stage of the disease.",2020,2020,MINT Medical GmbH,150714.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C01753,01KI2054C,Instant identification of biomarkers of COVID 19 by applying AI on structured reporting of Chest CT integrating clinical information,"clinical trial - Current evidence suggests that chest CT imaging may be an extremely valuable tool in the diagnosis, epidemiology, and therapy response control of COVID-19 cases. It offers high sensitivity, short turnaround times and wide availability, and may thus complement RT-PCR tests, especially in situations of unclear clinical presentation, such as a negative RT-PCR despite strong anamnestic evidence for COVID-19. More importantly, it may offer opportunities to directly assess the stage of progression of the disease as observed directly from the affected lung tissue, and may thus be a method of choice for therapy response assessment in upcoming trials of new therapeutic agents. However, in order to develop it into a suitable tool for these purposes, a reproducible, standardized, and quantitative approach to image diagnostics is required. This proposal aims to develop such a standardized diagnostic and staging procedure for COVID-19 cases, using an AI-supported approach to select clinical attributes that serve as optimal predictors of the presence and stage of the disease.",2020,2020,German Center for Cancer Research,255414.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C01754,01KI20182,Type III interferon(IFN-L) as a potential drug in SARS-CoV2 infection: Evaluation of antiviral and immune modulatory effects in a human in vitro model,"discovery - Clinical courses of infections with severe acute respiratory syndrome coronavirus (SARS-CoV2) are characterized by viral replication in lung epithelial cells. Infection is accompanied with the activation of early innate immune reactions, in particular the induction of type I interferons (IFN-a/ß) and type III IFN (IFN-lambda). These IFNs are a group of cytokines that strongly restrict viral replication but have pronounced, albeit differential immune modulatory activities. Thereby, they not only control infections but they induce the secretion of inflammatory cytokines from infiltrating immune cells. In the severe courses of disease, these overshooting inflammatory reactions represent one of the most critical clinical phenotypes, which often cause the hardly controllable pathological consequences of the infection. Due to a restricted cell target spectrum of type III IFNs the proinflammatory site effects of type I IFNs are strongly reduced and might thus offer an opportunity for specific treatment. This project aims at elucidating the potential benefit of type III IFN in treating SARS-CoV2 infections. An advanced cell co-culture model based on human epithelial cells and human iPS cell-derived macrophages will be used to elucidate the antiviral properties as well as the immune modulatory consequences of IFN-lambda. Single cell RNA sequencing will determine viral replication, epithelial cell death vs tissue repair as well as the activation profile of macrophages, i.e. their pro-inflammatory vs. anti-inflammatory phenotype.",2020,2020,"Helmholtz Zentrum für Infektionsforschung mbH, Braunschweig",256732.71,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C01755,01KI20126,"In-patient nursing, palliative and hospice care in the time of COVID-19: Social, ethical and legal implications from an intersectional perspective","social sciences - Challenges of SARS-CoV-2 are particularly pronounced in nursing care, even more so for palliative and hospice care, because patients in these settings are particularly susceptible for severe course of COVID-19 and measures necessary to decrease the spread of the virus hamper the very act of caregiving, creating legal, social and ethical dilemmas. These need to be addressed by diversity-sensitive concepts/policies. In the past weeks, providers of nursing, palliative and hospice care by necessity did develop approaches to adjust to a different reality. This study aims to examine these strategies, their perception by patients/relatives and to identify good practice approaches. Based on the findings and using a 6-step process of ethical decision-making, a handbook conceptualizing the determinants of good practice and providing recommendations on how challenges can be addressed will be developed. A mixed-method design is used. It comprises a scoping review of existing guidelines for nursing/palliative/hospice care (A), a document analysis of providers' websites (B), qualitative telephone/video interviews with patients and their relatives (n=10-12) (C), an online survey of in-patient nursing, palliative and hospice facilities in Germany (N=15.677+653) (D), and 8-10 focus group discussions with staff of selected facilities (n=5-7 per group= 40-70) (E). The triangulated findings will be discussed in a discussion circle with patients/relatives and experts in the field of ethics and law (F1) (n=8-10). Guidelines developed will be consented in a second discussion circle (F2).",2020,2021,Private Universität Witten/Herdecke,164860.47,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues in Clinical and Health System Decision-Making | Health service delivery,2020 +C01756,01KI20271,MoKoCo19 - Modellbasierte Datenanalyse für die bevölkerungsbezogene prospektive COVID-19-Kohortenstudie in München,"epidemiological study - Das Projekt MoKoCo19 hat das Ziel die Wirkung nicht-pharmakologischer Interventionen wie z. B. Schulschließungen und Kontaktbeschränkungen genauer zu quantifizieren und damit die Vorhersage des Pandemieverlaufs zu verbessern. Kern des Vorhaben sind modellbasierte Analysen der bevölkerungsbezogenen prospektiven Münchner COVID-19-Kohortenstudie in Kombination mit den vom Robert Koch-Institut gesammelten Daten. Die Resultate sollen dazu dienen politische Entscheidungsträger zu unterstützen den besten Weg aus der aktuellen Krise zu finden. epidemiological study - The MoKoCo19 project aims to evaluate the effects of non-pharmacological interventions such as school closures and contact restrictions and thus to improve the prediction of the to improve the course of the pandemic. At the core of the project are model-based analyses of the population-based prospective Munich COVID-19 cohort study in combination with the COVID-19 cohort study conducted by Robert Koch Institute collected data. The results should serve political decision makers to help find the best way out of the current crisis."" Translated with www.DeepL.com/Translator (free version)",2020,2021,Rheinische Friedrich-Wilhelms-Universität Bonn,50612.83,Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Impact/ effectiveness of control measures,2020 +C01757,01KI2098,"Management in oncology during COVID-19 pandemic - ethical, legal and health-economic implications","social sciences - Decision making on cancer care during the COVID-19 pandemic is characterized not only by limited resources and prioritizations of acute treatments, but also by multidimensional implications for treatment algorithms, long-term outcomes and clinical process management. This is not restricted to the phase of insufficient availability of resources during the pandemic, but has to be considered during all phases of the pandemic progression: 0) regular treatment before the pandemic; 1) prevention of the spread and preparation for infected individuals; 2) resource scarcity, and 3) of re-establishment of regular treatment routines. The complexity of cancer care requires specific considerations of ethical and medico-legal aspects during the pandemic, but currently such guidelines are only available for intensive/ emergency care. The proposed project aims to develop data-based decisional guidelines for oncology care under the context of pandemics. Stakeholder perspectives will be assessed by specific questionnaires. Clinical data from various sources (clinical cancer registry, claims data), data regarding oncology-specific critical resource availability during pandemic and selected economic data will be used for modelling consequences in terms of morbidity development, and disease-related outcomes. Based on our findings, a comprehensive evaluation of ethical and medico-legal aspects will lead to the development of a checklist for the management of oncology care during the pandemic and to the development of guidelines for this type of decision making under these critical conditions.",2020,2021,Medizinische Hochschule Hannover,455811.12,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues in Clinical and Health System Decision-Making | Health service delivery,2020 +C01758,01KI20135,Targeting protease-mediated activation of SARS-CoV-2,"discovery - Here, I propose to decipher the role of furin and related proteases in the activation of SARS-CoV-2 spike proteins. We will compare evolutionarily diverse coronaviruses to characterize proteolytic spike maturation and the downstream effects on viral infectivity. Taking advantage of our long-standing expertise in host-virus co-evolution, we will also characterize spike mutations that emerge during the current SARS-CoV-2 pandemic and may confer a selection advantage to the virus as they enhance furin-mediated cleavage. Notably, we previously identified a novel mechanism of antiviral immunity, demonstrating that guanylate-binding proteins 2 and 5 (GBP2/5) restrict a variety of viruses by targeting furin. We hypothesize that this mechanism also suppresses replication of SARS-CoV-2. In a translational approach, we will therefore test whether induction of GBP2/5 and/or inhibition of furin can limit the spread of SARS-CoV 2. The proposed project will not only provide important insights into the determinants of SARS-CoV-2 infectivity and tropism, but also help to assess consequences of mutations emerging during the current outbreak and might identify promising targets for therapeutic intervention.",2020,2021,Universitätsklinikum Ulm,410586.36,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C01759,01KI20160A,"Clinical, molecular, and functional biomarkers for prognosis, pathomechanisms, and treatment strategies in COVID-19","clinical trial - Infections with the novel Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) manifest with a broad spectrum of clinical presentations, ranging from asymptomatic to upper respiratory tract infections, uncomplicated pneumonia and severe pneumonia with respiratory failure and high lethality. Despite more than 1 Mio. documented infections worldwide, a profound lack of knowledge impedes clinical management and the development of therapies. COVID-19-associated pneumonia and lung injury differ in relevant details from any of the known types of pneumonia that cause respiratory failure, including viral infections like influenza or MERS-CoV. It is unclear whether specific decision guidelines established for pneumonia are applicable or whether these need to be refined for COVID-19. The PROVID consortium thus aims to characterize the host- and virus-dependent mechanisms associated with clinical appearance of COVID-19 to improve patient care through advances in risk stratification and clinical management. We will test the hypotheses that i) host factors (transcriptional response, proteins, antibodies) determine the severity and/or course of COVID-19, ii) molecular and clinical determinants of COVID-19 differ from those previously deciphered in other types of pneumonia and they can be used as molecular predictors for disease progression, iii) specific molecular markers of disease severity can be tested as therapeutic targets for COVID-19, iv) stabilization of barrier function - in addition to antivirals and immunomodulators - may present a third pillar for effective therapy.",2020,2021,Charité - Universitätsmedizin Berlin,1777176.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C01760,01KI20160B,"Clinical, molecular, and functional biomarkers for prognosis, pathomechanisms, and treatment strategies in COVID-19","clinical trial - Infections with the novel Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) manifest with a broad spectrum of clinical presentations, ranging from asymptomatic to upper respiratory tract infections, uncomplicated pneumonia and severe pneumonia with respiratory failure and high lethality. Despite more than 1 Mio. documented infections worldwide, a profound lack of knowledge impedes clinical management and the development of therapies. COVID-19-associated pneumonia and lung injury differ in relevant details from any of the known types of pneumonia that cause respiratory failure, including viral infections like influenza or MERS-CoV. It is unclear whether specific decision guidelines established for pneumonia are applicable or whether these need to be refined for COVID-19. The PROVID consortium thus aims to characterize the host- and virus-dependent mechanisms associated with clinical appearance of COVID-19 to improve patient care through advances in risk stratification and clinical management. We will test the hypotheses that i) host factors (transcriptional response, proteins, antibodies) determine the severity and/or course of COVID-19, ii) molecular and clinical determinants of COVID-19 differ from those previously deciphered in other types of pneumonia and they can be used as molecular predictors for disease progression, iii) specific molecular markers of disease severity can be tested as therapeutic targets for COVID-19, iv) stabilization of barrier function - in addition to antivirals and immunomodulators - may present a third pillar for effective therapy.",2020,2021,CAPNETZ Stiftung Ulm,472994.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C01761,01KI20160C,"Clinical, molecular, and functional biomarkers for prognosis, pathomechanisms, and treatment strategies in COVID-19","clinical trial - Infections with the novel Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) manifest with a broad spectrum of clinical presentations, ranging from asymptomatic to upper respiratory tract infections, uncomplicated pneumonia and severe pneumonia with respiratory failure and high lethality. Despite more than 1 Mio. documented infections worldwide, a profound lack of knowledge impedes clinical management and the development of therapies. COVID-19-associated pneumonia and lung injury differ in relevant details from any of the known types of pneumonia that cause respiratory failure, including viral infections like influenza or MERS-CoV. It is unclear whether specific decision guidelines established for pneumonia are applicable or whether these need to be refined for COVID-19. The PROVID consortium thus aims to characterize the host- and virus-dependent mechanisms associated with clinical appearance of COVID-19 to improve patient care through advances in risk stratification and clinical management. We will test the hypotheses that i) host factors (transcriptional response, proteins, antibodies) determine the severity and/or course of COVID-19, ii) molecular and clinical determinants of COVID-19 differ from those previously deciphered in other types of pneumonia and they can be used as molecular predictors for disease progression, iii) specific molecular markers of disease severity can be tested as therapeutic targets for COVID-19, iv) stabilization of barrier function - in addition to antivirals and immunomodulators - may present a third pillar for effective therapy.",2020,2021,Universität Leipzig,336464.4,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C01762,01KI20152,RECOVER: A Randomized Open-label Phase-II Trial with or without Infusion of Convalescent Plasma in High-Risk Patients with Severe COVID-19 Disease,"clinical trial - Convalescent plasma (CP) has been hypothesized to improve outcome in COVID-19 patients. Randomized trials are urgently needed for high-risk patients especially prior to full blown ARDS and mechanical ventilation. This multicenter phase II trial will analyze the effects of CP in high-risk patients with COVID-19 infection. Patients at high risk for a poor outcome due to underlying disease (group 1, pre-existing or concurrent hematological malignancy and/or ongoing chemotherapy for cancer; group 2, chronic immunosuppression not meeting criteria group 1; group 3, age 50-75 years and lymphopenia <0>1µg/mL not meeting criteria groups 1 or 2; group 4, age = 75 years not meeting criteria for either 1, 2 or 3) are eligible for enrollment. Eligibility also requires PCR confirmed SARS-CoV-2 infection and O2 saturation =93% while breathing ambient air. Patients are randomized to receive (experimental arm) or not receive (standard arm) convalescent plasma from two different donors (day1, day2). A cross-over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. The primary endpoint is the time to clinical improvement defined as two points improvement on a seven-point ordinal scale of patient state of health or discharge alive from the hospital. Secondary outcomes are mortality, changes in clinical scores, inflammatory cytokine changes and viral load dynamics. This trial systematically assesses the therapeutic role of convalescent plasma for treating SARS-CoV-2 infection in a high-risk patient population.",2020,2021,Universitätsklinikum Heidelberg,2402898.3,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,"Clinical Trial, Phase II | Randomized Controlled Trial",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Clinical trials for disease management,2020 +C01763,01KI2059,Innate immune activation and restriction of SARS CoV-2,"discovery - Coronaviruses (CoVs) show striking differences in their pathogenicity, ranging from harmless colds to severe respiratory infections after viral zoonoses with fatality rates of up to 40% in the case of MERS-CoV. With death rates of ~9% and ~0.3-3.4%, respectively, SARS-CoV and the emerging SARS-CoV-2 fall between these extremes. The reasons for this different pathogenicity are poorly understood. However, host immunity and viral adaptation to humans most likely play key roles. Studies on highly pathogenic SARS-CoV and MERS-CoV revealed that they evolved various mechanisms to suppress innate immune sensing and interferon production as well as to antagonize antiviral factors. Counteraction of our immune defense impedes viral control and may be a prerequisite for high virulence. I hypothesize that counteraction of innate immunity together with untimely activation of inflammation have a major impact on CoV pathogenesis. To address this, I propose to perform comparative analyses of human CoVs, MERS-CoV, SARS-CoV, SARS-CoV-2 and their closest animal counterparts for their ability to suppress or counteract innate immunity. Initially, we will determine the expression of viral immune sensors and antiviral factors in primary lung cells. To define determinants of virus transmission and pathogenesis, we will analyze the capability of proteins from various CoVs to manipulate immune sensors, signaling molecules, and antiviral effectors. In addition, we will examine whether it is possible to modulate the innate immune response to achieve efficient control or tolerance of SARS-CoV-2.",2020,2021,Universität Ulm,605917.12,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C01764,01KI20269,scCoV2-Einzelsequenzierung von SARS-CoV2-infizierten Zellen,"discovery - This is a basic scientific research project on SARS-CoV-2. The aim of the project is to investigate in detail the mutual influences between the viruses and the metabolism of human host cells in SARS-CoV-2 infection. Specifically, the ribonucleic acids (RNA) of individual cells from cell lines infected with SARS-CoV-2 are to be examined (sequenced) and analyzed in detail in the project. Based on the findings, cell culture models are to be developed that can be used for further questions on SARS-CoV-2 infections.",2020,2021,"Max-Delbrück-Centrum für Molekulare Medizin, Berlin",54122.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C01765,01KI20185A,"SECOVIT - Sequence-based analysis of interactions of SARS-CoV-2, respiratory viral co-infections, and T-cell immunity: clinical implications","discovery - The outbreak of the new virus SARS-CoV-2 is a major problem at a global scale. Viral evolution is a major characteristic of all RNA viruses leading to accelerated evolution and adaptability to new environments. Our working hypothesis is that specific SARS-CoV-2 variants will be selected, as the virus is passing through a vast set of individuals with diverse HLA alleles and co-infections. The mutations fixed in this process can affect viral properties such as transmission or replication rates, that finally may modulate coronavirus disease (COVID-19) progression. The overall goal of this interdisciplinary consortium is to elucidate whether the HLA background and respiratory viral co-infections play a role in SARS-CoV-2 evolution and adaptation to different Human populations as well as in the severity of COVID-19. The specific scientific questions of the consortium are: 1) to characterise the genetic variability of SARS-CoV-2 in NRW over time of the current outbreak and from possible future infections, and in comparison to other geographic regions; 2) to define the role of HLA as driving force for SARS-CoV-2 evolution and as a determinant for disease severity, using data from our patients as well as prevalence data from other countries; and 3) to define the role of respiratory viral co-infections and their implications for the severity of COVID-19 outcome and SARS-CoV-2 evolution. This will enable to optimise medical and quarantine measures. HLA associations with SARS-CoV-2 genomes can be exploited for the design of T-cell based vaccines",2020,2021,Universität zu Köln Universität Duisburg-Essen,532027.66,Human Populations | Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity | Disease pathogenesis",2020 +C01766,01KI20185B,"SECOVIT - Sequence-based analysis of interactions of SARS-CoV-2, respiratory viral co-infections, and T-cell immunity: clinical implications","discovery - The outbreak of the new virus SARS-CoV-2 is a major problem at a global scale. Viral evolution is a major characteristic of all RNA viruses leading to accelerated evolution and adaptability to new environments. Our working hypothesis is that specific SARS-CoV-2 variants will be selected, as the virus is passing through a vast set of individuals with diverse HLA alleles and co-infections. The mutations fixed in this process can affect viral properties such as transmission or replication rates, that finally may modulate coronavirus disease (COVID-19) progression. The overall goal of this interdisciplinary consortium is to elucidate whether the HLA background and respiratory viral co-infections play a role in SARS-CoV-2 evolution and adaptation to different Human populations as well as in the severity of COVID-19. The specific scientific questions of the consortium are: 1) to characterise the genetic variability of SARS-CoV-2 in NRW over time of the current outbreak and from possible future infections, and in comparison to other geographic regions; 2) to define the role of HLA as driving force for SARS-CoV-2 evolution and as a determinant for disease severity, using data from our patients as well as prevalence data from other countries; and 3) to define the role of respiratory viral co-infections and their implications for the severity of COVID-19 outcome and SARS-CoV-2 evolution. This will enable to optimise medical and quarantine measures. HLA associations with SARS-CoV-2 genomes can be exploited for the design of T-cell based vaccines",2020,2021,Universität Duisburg-Essen,142362.35,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis | Supportive care, processes of care and management",2020 +C01767,01KI20172A,Analysis of innate immune sensing of SARS-CoV-2 using recombinant viruses,"discovery - The fast pandemic spread of SARS-CoV-2 is fostered by its rather high reproduction number R0 but also by a significant proportion of oligo- or asymptomatic infections that complicate containment. The circumstance that the virus is able to replicate without notable signs of inflammation suggests that the initial innate immune control of viral replication might be deregulated and less effective. Thus, this study aims at characterizing mechanisms that allow SARS-CoV-2 to evade innate immune sensing by the host. Proteins in CoVs that counteract immune sensing include the Endonuclease U (Nsp15) and 2OMethyltransferase (Nsp16), which inhibit the detection of CoV RNA by host RNA sensors upon infection. In addition, mutations in the accessory protein ORF8 have been linked to a reduced replication of SARS-CoV. Here, we will analyze the effects of these immunomodulatory factors in shielding SARS-CoV-2 from innate immunity by generating recombinant viruses lacking the respective functional ORFs. We will test the replication capacity and the ability to avoid detection by innate immunity in vitro and in vivo using transgenic human ACE-2 mice. Making the virus more ""visible"" to intrinsic immunity will allow the immune system to better control viral replication and clear the virus more efficiently. Identifying viral proteins, which inhibit innate sensing of SARS-CoV-2, will be of high interest to both vaccine development and therapy.",2020,2021,Friedrich-Alexander-Universität Erlangen-Nürnberg,496512.22,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Immunity | Pathogen morphology, shedding & natural history",2020 +C01768,01KI20172B,Analysis of innate immune sensing of SARS-CoV-2 using recombinant viruses,"discovery - The fast pandemic spread of SARS-CoV-2 is fostered by its rather high reproduction number R0 but also by a significant proportion of oligo- or asymptomatic infections that complicate containment. The circumstance that the virus is able to replicate without notable signs of inflammation suggests that the initial innate immune control of viral replication might be deregulated and less effective. Thus, this study aims at characterizing mechanisms that allow SARS-CoV-2 to evade innate immune sensing by the host. Proteins in CoVs that counteract immune sensing include the Endonuclease U (Nsp15) and 2OMethyltransferase (Nsp16), which inhibit the detection of CoV RNA by host RNA sensors upon infection. In addition, mutations in the accessory protein ORF8 have been linked to a reduced replication of SARS-CoV. Here, we will analyze the effects of these immunomodulatory factors in shielding SARS-CoV-2 from innate immunity by generating recombinant viruses lacking the respective functional ORFs. We will test the replication capacity and the ability to avoid detection by innate immunity in vitro and in vivo using transgenic human ACE-2 mice. Making the virus more ""visible"" to intrinsic immunity will allow the immune system to better control viral replication and clear the virus more efficiently. Identifying viral proteins, which inhibit innate sensing of SARS-CoV-2, will be of high interest to both vaccine development and therapy.",2020,2021,Fraunhofer Gesellschaft München,207904.56,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C01769,01KI20139,Silvestrol als Wirkstoff gegen SARS-CoV-2/ COVID-19,"discovery - The aim of the project is to investigate whether chemically modified variants of the natural product Silvestrol are suitable for therapy against SARS-CoV-2. Previous research with SARS-CoV-2-related RNA viruses has shown that silvestrol inhibits an endogenous protein (eIF4F), which the previously examined viruses need for their multiplication in the host cells. Now the researchers want to check whether this also applies to SARS-CoV-2. To do this, they will produce chemically modified Silvestrol molecules and test their effectiveness against SARS-CoV-2 and other RNA viruses in cell cultures and in animal models. The project builds on the BMBF-funded project ""16GW0203 - Preclinical Animal Model Systems"" (16GW0203) in the SILVIR network. Accordingly, the preparatory work and cooperation established there can be used.",2020,2021,"Friedrich-Loeffler-Institut, Greifswald",55870,Animals | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C01770,01KI2093,"Understanding what happens and acting upon it: ethical, legal, and socio-economic dimensions of the COVID-19 outbreak from the citizens' perspective","social sciences - In this rapid response research project, we use a mixed-methods approach to document, preserve, & share ephemeral data on the social dimensions of an emergent outbreak, and to translate this knowledge into tangible countermeasures that can aid in minimizing the negative impacts of the disease. Our mixed-methods approach includes (1) a national, representative, repeated measures survey of up to 1,050 German households (3.5% of 30,000 households contacted), (2) follow-up interviews across Germany (n = 90 over 3 intervals), (3) a diary method to understand the nuances of everyday life under dramatically new conditions, (4) an online ethnography on Twitter to understand how a range of public health & affective content is received/communicated by diverse audiences (5) content analysis of mainstream media/public health releases. This approach will help us to understand a range of research questions covering the ethical, legal & socio-economic dimensions of the COVID-19 outbreak, including how individuals & communities perceive risks and protective behaviours related to COVID-19 with regards to individual human rights, pro-social ethical duties & their own socio-economic situations; how public understandings of the disease evolve as a result of information production, reception and internalisation processes; how these vary across diverse populations and demographics; how German citizens are experiencing stigmatization and negative outcomes. The results will inform discussions pertaining to what local knowledge can be mobilized to help, & how pro-social behaviours can be fostered.",2020,2021,Sigmund Freud PrivatUniversität Berlin,463875.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C01771,01KI20150C,Identifying host factors as drug targets and drugs employing RNAi knockdown screens,"discovery - We aim to identify and effectively inhibit host dependency factors being essential for SARS-CoV-2 replication and spread, following a systematic screening approach. Human epithelial cells will be seeded in ""ready to transfect"" multiwell plates, designed and produced in the laboratory of HE. Those plates are containing dried siRNA/transfection reagent complexes. When the cells attach to the surface, reverse transfection enables siRNA mediated knockdown of a single gene, in high-throughput. Then, the cells will be infected with clinical SARS-CoV-2 isolates collected by SC and cCytopathic effect and MTT assays performed. After inactivation by paraformaldehyde, these transportable plates will be sent to the lab of HE who will elaborately phenotype the cells using an established imaging pipeline. RK will compare the hits from the screen to time-lapse proteomics data of SARS-CoV-2 infected human epithelial host cells (data was derived from SC recently), omics data from other coronavirus infection studies, and gene associations to the Severe Acute Respiratory Syndrome. This will lead to a short list of host dependency factors for which drugs will be selected employing publicly available drug databases. Selected host factors and drugs will be validated in the lab of SC employing a broad selection of SARS-CoV-2 isolates. In addition, RK will infer a SARS-CoV-2 specific protein interaction network and identify clusters of host factors to get drug combinations, which will be experimentally validated by SC. We will yield an effective drug treatment for COVID-19 therapy and prevention.",2020,2021,Universität Heidelberg,268256.45,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C01772,RIA2020EF-2968,RE-BCG-CoV-19: BCG revaccination for healthcare workers in SARS-CoV-2 pandemic,The RE-BCG-CoV-19 project (RIA2020EF-2968) aims to investigate whether and why BCG-revaccination can reduce infection rate and/or disease severity in healthcare workers during the SARS-CoV-2 virus disease outbreak in South Africa.,2020,-99,Task Foundation NPC,545000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,South Africa,South Africa,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C01773,RIA2020EF-3049,BCG-COVID-RCT: BCG vaccine to reduce absenteeism due to infectious diseases of health workers during the COVID-19 pandemic. A multi-centre randomised controlled trial,The BCG-COVID-RCT project (RIA2020EF-3049) aims to study the BCG non-specific protection of healthcare workers against COVID-19.,2020,-99,University of Southern Denmark,583727.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,Denmark,Guinea-Bissau | Cabo Verde | Mozambique,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C01774,RIA2020EF-2928,HALT_COVID-19 Natural history and laboratory tests for COVID-19 in South Africa,The HALT_COVID-19 project (RIA2020EF-2928) aims to utilize a combination of approaches to characterise clinical disease progression and clinical outcomes among patients with SARS-CoV-2 viral infection and to perform a clinical evaluation of COVID-19 testing kits in South Africa.,2020,-99,Centre for the AIDS Programme of Research in South Africa,594930.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa | Europe,Africa | Europe,,,,South Africa | Denmark | Germany | Netherlands,South Africa | Denmark | Germany | Netherlands,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis,2020 +C01775,RIA2020EF-3020,Covid-19 HCW: Surveillance among healthcare workers for SARS-Coronavirus-2-infection,"The Covid-19 HCW project (RIA2020EF-3020) aims to investigate the epidemiology of SARS-CoV-2 infection among (i) healthcare workers who triage patients with suspected SARS-CoV-2 infection and provide care to COVID-19 patients, and ii) laboratory personnel who test clinical samples for SARS-CoV-2 infection.",2020,-99,Wits Health Consortium (Pty) Limited,549932.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Unspecified,,,,South Africa,,Epidemiological studies,Disease transmission dynamics,2020 +C01776,RIA2020EF-2981,TraCE. Transmission of COVID-19 in crowded environments,"The TraCE project (RIA2020EF-2981) aims to understand and mitigate household transmission of SARs-CoV2 infection in a low-income, high-density South African community setting. Data to be collected over 8 months will be used to determine the Ro for SARS-CoV-2 infection, the rate of symptomatic disease, and the impact of an infection mitigation intervention administered by community healthcare workers.",2020,-99,Desmond Tutu Health Foundation NPC,555780.96,Human Populations,Unspecified,Unspecified,Other,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,South Africa,South Africa,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C01777,RIA2020EF-2983,CSIGN COVID surveillance intensification in Ghana Network,"The CSIGN project (RIA2020EF-2983) aims to build the Ghana COVID-19 surveillance and response system, by amplifying and redirecting the already excellent influenza surveillance toward the new pathogen, by enhancing response activities through contact tracing, and by building capacity in laboratory testing and sequencing.",2020,-99,London School of Hygiene & Tropical Medicine,594426.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa | Europe,Africa,,,,United Kingdom | Ghana | Spain,Ghana,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C01778,RIA2020EF-2947,ITAIL-COVID-19: Integrated testing approaches and intensive laboratory training as strategy against SARS-CoV-2 spread in Brazzaville,"The ITAIL-COVID-19 project (RIA2020EF-2947) aims to better understand the COVID-19 infection epidemiology in Congo-Brazzaville and to strengthen the country's national surveillance system. Surveillance will be carried out by assessing the circulation of the virus in the community, in various ways (patients with flu-like symptoms and a symptom-free control group).",2020,-99,Fondation Congolaise pour la Recherche Médicale,595000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Congo,Congo,Epidemiological studies,Disease transmission dynamics,2020 +C01779,RIA2020EF-2905,Profile-Covid Rapid diagnostic profiling of SARS-CoV-2 in the context of persistent immune activation in sub-Saharan Africa,The Profile-Cov project (RIA2020EF-2905) aims to evaluate the profile of the immune response of the Ethiopian population and will examine its relationship with the noted low CD4+ T-cell count and underlying immune activation status among patients with COVID-19 and will compare the results with data collected in Europe.,2020,-99,Mekelle University,559529.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Ethiopia,Ethiopia | Ghana,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C01780,RIA2020EF-2918,AfriDx: COVID-19 diagnostics for Africa,The AfriDx project (RIA2020EF-2918) aims to conduct a trial of a prototype point-of-care LAMP test (PATHPOD) for detection of viral RNA (SARS-Cov-2) in the COVID-19 testing laboratories in Ghana; develop a production process for local manufacture in Ghana of the required biological materials at low cost; produce a version of PATHPOD in Africa for Africa (the AfriDx).,2020,-99,University of Cambridge,584921.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,United Kingdom,Senegal | Madagascar | Nigeria | Ghana | Uganda | Sudan | Congo (DRC),"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01781,RIA2020EF-2937,Africa_Suitcaslab: Multi-country blinded study to evaluate the suitcase lab for rapid detection of SARS-CoV-2,"The Africa_Suitcaslab project (RIA2020EF-2937) aims to validate a solar-powered suitcase RT PCR lab for the detection of SARS-COV-2. Conducted in seven African countries, the study will include capacity building by providing a BSL-3 level glove box to allow safe inactivation of the clinical samples as well as strengthening the diagnostic capabilities of the involved partners.",2020,-99,Universität Leipzig,590000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,Germany,Sudan | Uganda | Congo (DRC),"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01782,RIA2020EF-3042,ImmunoCoV: Host immune responses to SARS-CoV-2: correlating kinetics with the natural history of infection,"The ImmunoCoV project (RIA2020EF-3042) aims to 1) test and validate antibody and other immunological assays for the diagnosis and further research on the immunology of SARS-CoV-2 infections in African populations, and 2) provide detailed kinetics of the immune response to SARS-CoV-2 in relation to viral shedding, clinical symptoms and asymptomatic infections.",2020,-99,African Research Collaboration for Health Ltd.,556976,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Kenya,Kenya,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C01783,RIA2020EF-2923,STRESSCO: Strengthening epidemiological surveillance in Benin and Burkina Faso for an effective response to COVID-19,"The STREESCO project (RIA2020EF-2923) aims to develop a system for epidemic surveillance and response that will be effective, sensitive, coordinated and adapted to the low-resource context in Benin and Burkina Faso.",2020,-99,Institut de Recherche Clinique du Bénin,599992.8,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Other,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Benin,Benin | Burkina Faso,,,2020 +C01784,RIA2020EF-2926,"periCOVID-Africa: Understanding COVID-19 infections in pregnant women and their babies in Uganda, Kenya, Malawi, The Gambia and Mozambique","The periCOVID-Africa project (RIA2020EF-2926) aims to develop COVID-19 surveillance in pregnancy in The Gambia, Kenya, Malawi, Mozambique and Uganda embedded in existing cohort studies.",2020,-99,St George?s Hospital Medical School,579923.44,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,United Kingdom,Gambia | Kenya | Malawi | Mozambique | Uganda,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C01785,RIA2020EF-2961,AIDCO: Important data on COVID-19 profile in Africa,"The AIDCO project (RIA2020EF-2961) aims to characterise COVID-19 in different parts of Africa, studying the clinical outcome of COVID-19 and the pattern of infection in households with confirmed cases in Senegal, Gabon and Ethiopian.",2020,-99,Centre de recherches médicales de Lambaréné (CERMEL),559998.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Gabon,Gabon | Senegal | Ethiopia,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis,2020 +C01786,RIA2020EF-3008,Investigating COVID-19 infectiousness and antibody evolution in COVID-19 patients in SSA and Europe,"The COVAB project (RIA2020EF-3008) aims to understand antibody evolution following exposure to and/or SARS-CoV-2 infection, and to investigate factors associated with infection by SARS-CoV-2 across oral and nasal mucosa biopsies.",2020,-99,N/A,499605.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,,Africa,,,,,Uganda | South Africa,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C01787,RIA2020EF-3012,COVADIS: COVID-19 epidemic in West Africa: infection dynamics and diagnostic approaches,"The COVADIS project (RIA2020EF-3012) aims to validate an antigen-based point of care test in suspected West African COVID-19 patients; to develop a validated serological platform for COVID-19 serodiagnostic and outbreak surveillance, to characterise the viral load and antibody dynamics in a cohort of confirmed COVID-19 patients and to characterise at the household level the seroepidemiology of COVID-19 infections.",2020,-99,London School of Hygiene & Tropical Medicine,559876.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,United Kingdom,Burkina Faso | Gambia,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Immunity | Disease transmission dynamics,2020 +C01788,RIA2020EF-3004,TREATS-COVID Understanding the epidemiology of SARS-CoV-2 and the interrelation of COVID-19 with TB and HIV in Zambia,"The TREATS-COVID project (RIA2020EF-3004) aims to conduct epidemiological and social research that will improve our understanding of SARS-CoV-2 transmissibility, susceptibility, disease severity, and risk factors and the interrelationship between SARS-CoV-2 and TB/HIV",2020,-99,ZAMBART,595000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa | Europe,Africa,,,,Zambia | France | Netherlands | United Kingdom,South Africa,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C01789,RIA2020EF-3026,COREP: Determining the epidemiological parameters of COVID-19 through sero-surveillance with dried plasma spots and nested household transmission studies in rural Kenya and South Africa,"The COREP project (RIA2020EF-3026) aims to 1) define epidemiological parameters of SARS-CoV-2 infection in rural Kenya and South Africa, including the reproductive number, transmissibility, clinical disease spectrum and population-level incidence; 2) assess the burden of SARS-CoV-2 disease in rural areas of sub-Saharan Africa, and risk factors for infection and transmission; and 3) evaluate the diagnostic performance, feasibility, usability and cost-effectiveness of Dried Plasma Spot samples collected at the community level through fingerpricks by community health workers, followed by centralised serological testing.",2020,-99,Heidelberg University Hospital,594125.35,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa,,,,Germany,Zambia,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C01790,RIA2020EF-3030,"RADIATES Consortium: Development, evaluation and impact of RT-LAMP diagnostics and sequence surveillance on SARS-CoV-2 transmission in South Africa",The RADIATES Consortium (RIA2020EF-3030) aims to optimise and evaluate a cost-effective reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform for point-of-care testing in resource-limited settings.,2020,-99,National Health Laboratory Service (NHLS),561234.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,South Africa,South Africa,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01791,RIA2020EF-3031,AfriCoVER: Characterising transmission parameters of SARS-CoV-2 in peri-urban setting in Mozambique using population-based surveillance and high-throughput sero-assay,"The AfriCoVER project (RIA2020EF-3031) aims to conduct population-based surveillance in a Demographic Health Surveillance System (HDSS) of 16,500 people in a peri-urban neighbourhood of Maputo, Mozambique, by collecting clinical information and respiratory specimens from patients during biweekly household visits, complemented with data from local clinics.",2020,-99,Prins Leopold Instituut voor Tropische Geneeskunde (ITM),554988.9,Human Populations,Unspecified,Unspecified,Suburban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Mozambique,Mozambique,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease pathogenesis,2020 +C01792,50286,COVID-19 in the Gaza Strip: community practices in Palestine refugee camps,"This qualitative study aims to identify the barriers and enablers for the uptake of public health measures in Palestine refugee camp communities in the Gaza Strip. It will also look at protection concerns for vulnerable groups arising as a result of public health measures being implemented in the communities. Expected outcomes are a better- informed UNRWA response to COVID-19 in Palestinian refugee communities, supported by an increased evidence base of current community practices surrounding COVID-19, and data on the interconnection between public health measures and protection issues.",2020,2020,University of Bath,75968.48,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Eastern Mediterranean,,,,United Kingdom,Palestine,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C01793,50195,"Cash transfers and COVID-19: Experiences from Kiryandongo refugee settlement, Uganda","This study, which is an add-on element to an existing randomised controlled trial (RCT), focuses on which refugee households are implementing COVID-19 public health measures and how unconditional cash transfers affect this. It will also explore household understanding of COVID-19, social distancing measures being implemented, and their effects on household daily life. Expected outcomes are increased understanding of both how large, unconditional cash transfers influence refugee households to implement COVID-19 public health measures, such as social distancing; and of effects of COVID-19 on the daily lives of refugee households, including whether existing programmes and messaging are effective in increasing knowledge and changing behaviours.",2020,2020,IDinsight,113296.27,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,International,Africa,,,,International,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C01794,50530,"Knowledge, adherence and the lived experiences of refugees in COVID-19: A comparative assessment of urban and rural refugee settings in Uganda","This is a mixed-method rapid situation analysis conducted in Uganda's diverse refugee settings, targeting Somalis, South Sudanese, Congolese, Rwandans and Burundians. The team seeks to study refugee lived experiences, assess behavioural shifts and local risk perceptions, and determine how refugees are responding to COVID-19 public health measures in Uganda. Expected outcomes are models, frameworks and actionable recommendations for humanitarian actors, based on deeper understanding of the impact of the pandemic on social behaviours in refugee settings, particularly regarding local innovations to implement public health measures; the role of community-based responses and networks; the 'infodemic'; and negative coping mechanisms.",2020,2020,Makerere University,196121.23,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Africa,Innovation,,,Uganda,Uganda,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Communication | Economic impacts | Health service delivery",2020 +C01795,50522,Implementation of public health measures among internally displaced people during the COVID-19 pandemic in Francophone Africa: Pilot study of Mali,"This qualitative exploratory study aims to contribute to the Malian government's public health measures in response to COVID-19. The study aims to understand the challenges and responses to public health measures of IDPs living in Bamako and Ségou, to inform efforts to contextualise and adapt these measures to make them more effective among IDPs. The study will be a pilot for a regional initiative 'COVID Francophone Africa' led by the network Francophone Africa and Fragility. The expected outcomes are improved, evidence-based understanding of the challenges faced by authorities and humanitarian actors in adequately implementing public health measures to inform and adapt in real time the response to COVID-19, and based on this, proposals for appropriate adjustments and best practice guidance.",2020,2020,Faculty of Medicine & Odontostomatology (FMOS) of Bamako,51251.79,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Africa,,,,Mali,Mali,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C01796,50505,Using radio and social media to address misinformation about COVID-19 amongst Internally Displaced Persons in Burkina Faso,,2020,2021,University of Sheffield,129276.72,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Africa,Digital Health,,,United Kingdom,Burkina Faso,"Policies for public health, disease control & community resilience",Communication,2020 +C01797,51538,"Tracking adherence of older refugees to COVID-19 preventive measures in response to changing vulnerabilities: A multi-level, panel study to inform humanitarian response in Lebanon","This study will focus on Syrian refugees in Lebanon aged 50+. Using multi-level analysis, the study will explore how adherence to COVID-19 prevention and control measures among older Syrian refugees varies over time in response to emergent vulnerabilities in the context. The study addresses an important need by addressing a neglected group in humanitarian emergencies - older adults - who are high risk in the COVID-19 outbreak. The expected outcomes are an improved humanitarian response to COVID-19 by NRC, based on evidence and data. Additionally, evidence and knowledge sharing, including through infographics and social media 'bites', will facilitate a coordinated response to COVID-19 among other humanitarian actors in the same location.",2020,2021,Norwegian Refugee Council,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Eastern Mediterranean,Eastern Mediterranean,,,,Lebanon,Lebanon,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Social impacts,2020 +C01798,51529,"Understanding the impact of misinformation on the uptake of and adherence to COVID-19 related public health measures in refugee and IDP settings across Kenya, Somalia and the Democratic Republic of Congo","This mixed-methods study will take place in six sites in three countries with large refugee and IDP populations - Kenya, Somalia and DRC. The team will examine how misinformation on COVID-19 spreads, as well as sources and channels of misinformation. The study will also identify effective countermeasures. The evidence will enable better understanding of how misinformation is currently being spread through the selected study areas. Expected outcomes are frameworks and strategies to deliver targeted, accurate, clear and actionable health information to increase adherence to public health measures, and to combat the spread of misinformation related to COVID-19.",2020,2020,Busara Center for Behavioral Economics,101566.15,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Africa,,,,Kenya,Kenya | Congo (DRC) | Somalia,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C01799,51487,Strengthening the humanitarian response to COVID-19 in Colombia,"This study uses qualitative and quantitative data to determine variation in implementation, and adherence to public health and social distancing policies among Venezuelan migrant refugees in 60 Colombian municipalities. The study will produce better understanding of the effectiveness of stated policies and observed behaviours on the evolution of the COVID-19 epidemic in each of 60 municipalities, and analysis of health care costs for the migrant populations. Expected outcomes are the ability to identify policies and behaviours that have achieved a favourable balance of controlling transmission, while minimizing economic distress on the displaced populations.",2020,2020,Brandeis University,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Americas,Americas,,,,Colombia,Colombia,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Approaches to public health interventions | Policy research and interventions | Social impacts | Other secondary impacts,2020 +C01800,51563,Tracking Community Perceptions: A vital voice in curbing the spread of COVID-19 and other infectious diseases,"This mixed-methods study will use an intervention called the Community Perception Tracker (CPT) to assess community perceptions during the COVID-19 outbreak around the acceptability of programmes, and behaviour change interventions on key topics, such as handwashing, in Zimbabwe and Lebanon.. Expected outcomes are improved understanding of behavioural enablers and barriers for people affected by COVID-19, to minimise infection risks, timely adaptation and increased quality of programme interventions, in line with communities' understanding, priorities and needs. Additionally, enhanced support to field teams to immediately analyse and use the data delivered through the study, and a monitoring and evaluation framework for the use of the CPT in public health programmes.",2020,2021,Oxfam,397428.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Africa | Eastern Mediterranean,,,,United Kingdom,Lebanon | Zimbabwe,"Policies for public health, disease control & community resilience",Community engagement,2020 +C01801,51551,"Using Humanitarian Engineering to Solve Social Distancing Barriers in Refugee Humanitarian Interventions: A Cross-Country Comparison of Turkey, Lebanon and Jordan (Conditional)","This study uses qualitative and quantitative methods to explore how humanitarian non-governmental organisations (NGOs) in three countries tackle the challenge of limiting infection spread of COVID-19 among refugee populations. Using humanitarian engineering, cross-country comparisons will be used to examine how NGOs are addressing infection risks, with a view to informing best practice guidance for humanitarian interventions. Expected outcomes are better understanding of the challenges that NGOs face in trying to minimize spread of infectious disease while administering humanitarian assistance to refugees during a pandemic, and recommendations for NGOs and government officials for overcoming those challenges.",2020,2020,Michigan State University,158994.66,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Americas,Eastern Mediterranean | Europe,Innovation,,,United States of America,Turkey | Lebanon | Jordan,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C01802,51589,Monitoring and maintenance of handwashing devices during the COVID-19 crisis in a humanitarian context - the role of psychological ownership (Conditional),"This controlled trial study aims to increase handwashing in households, and will be conducted in Cox's Bazaar, Bangladesh. Camp residents and staff will be surveyed to assess functionality, monitoring and maintenance systems of handwashing devices as well as psychological ownership of the devices, to assess whether ownership increases handwashing. The expected outcomes are improved monitoring and maintenance of both individual and public handwashing devices in the camp settings, and strengthened interventions for handwashing which increase psychological ownership, tailored to the local conditions and the current COVID-19 crisis.",2020,2020,Swiss Federal Institute of Aquatic Science and Technology (Eawag),,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,South-East Asia,,,,Switzerland,Bangladesh,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +C01803,51553,Evaluating the impact of COVID-19 on multi-sectoral humanitarian needs,"This study will use desk-based research with three country case studies to better understand the impacts on people and communities of the COVID-19 pandemic, taking a multi-sectoral approach (drawing on the REACH Multi-Sectoral Needs Assessments). The study team hopes to identify priority sectors and vulnerable groups or populations. The expected outcomes are a better understanding of the multi-sectoral vulnerability to Covid-19 in the 7 MSNA countries, which can inform research design of the 2020 MSNA process and inform emergency prioritization; and an understanding of how Covid-19 is exacerbating humanitarian needs in these crises, to inform targeting and decision-making of humanitarian response to COVID-19, both within the health sector and other sectors.",2020,2021,IMPACT Initiatives,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Africa | Eastern Mediterranean | South-East Asia,,,,Switzerland,Afghanistan | Bangladesh | Central African Republic | Libya | Iraq | Nigeria,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C01804,51572,Gender-based violence (GBV) risk mitigation among non-protection humanitarian sectors in the context of COVID-19,"This mixed-methods study seeks to understand how global guidance on GBV from the Inter-Agency Standing Committee (IASC) on COVID-19 response programming is being implemented in non-protection sectors including through interviews with humanitarian practitioners. It aims to help inform and adapt the guidance for humanitarian response in the non-protection sectors, for both the COVID-19 and future outbreaks. The expected outcomes are strengthened global guidance on GBV risk mitigation for use during the current COVID-19 response and future responses; and programme adaptions and improvements by UNICEF, CARE and other humanitarian stakeholders in response to evidence and recommendations emerging from the study.",2020,2021,Beth Israel Deaconess Medical Center,150882.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Eastern Mediterranean,Unspecified,Gender,,,Israel,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C01805,50520,Health system and community responses to COVID-19: a comparative study focused on Palestinian refugees in Gaza and Lebanon,"This study adopts a realist case-study and mixed-method design to appraise the effectiveness, equity, acceptability and scalability of strategies put in place by health systems in the context of the global COVID-19 pandemic, to sustain routine service delivery and mitigate the impacts of COVID-19. The study will produce timely evidence, in usable formats such as summaries, infographics, and survey analysis reports, to inform ongoing decision-making of UNRWA and other humanitarian actors. Longer-term outcomes include improved understanding of the resilience of health systems responding to the needs of protractedly displaced populations, and on the effective strategies and underlying capacities required for health systems to respond.",2020,2021,Queen Margaret University,52070.2,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Eastern Mediterranean,,,,United Kingdom,Palestine | Lebanon,Health Systems Research,Health service delivery,2020 +C01806,51420,Dial-COVID: remote mitigation through telephone symptom surveillance in refugee settlements in Uganda,"This study, based in Uganda, focuses on evaluating the acceptability and effectiveness of a mobile telephone interactive voice response (IVR) symptom tracker/information dissemination tool (""Dial-COVID"") for supporting COVID-19 prevention and control measures. The team are testing established technology, already used in LMICs, in a refugee population, to apply the findings to the current COVID-19 response. The expected outcomes are the implementation and validation of Dial-COVID as a COVID-19 surveillance and information dissemination tool, which could be used in other settings; plus improvements in effectiveness and targeting of COVID-19 public health information and interventions for refugees in Uganda.",2020,2021,University of Washington,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Americas,Africa,Digital Health,,,United States of America,Uganda,"Policies for public health, disease control & community resilience",Communication,2020 +C01834,221307/Z/20/Z,COPCOV: Chloroquine/Hydroxychloroquine prevention of COVID-19 in the healthcare setting,"There is no proven treatment, chemoprophylaxis or vaccine for COVID-19. This is the most serious pandemic emergency for 100 years. Healthcare workers are being affected disproportionately in the continuing epidemic threatening an imminent breakdown of health services. Chloroquine and hydroxychloroquine are safe and well-tolerated medications which can be taken for years without adverse effects.Both have significant antiviral activity against SARS-CoV-2 and there is emerging evidence from China and Europe of efficacy in treatment. Unfortunately there is also premature recommendation from countries such as India which now recommends low dose hydroxychloroquine for prophylaxis in health care workers. We propose conducting a multi-centre, multi-country randomised, double blind, placebo controlled assessment of the prophylactic efficacy of chloroquine (Asia) or hydroxychloroquine (Europe) in preventing COVID-19 illness in at-risk healthcare workers and other frontline staff. At least 40,000 participants in Asia and Europe will be randomised 1:1 to receive chloroquine or hydroxychloroquine or a matched film coated placebo as daily prophylaxis for three months. The study's objectives are the prevention of symptomatic coronavirus disease (COVID-19) and the attenuation of the clinical severity.",2020,2021,Mahidol Oxford Tropical Medicine Research Unit,9065376.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation | COVID-19 Therapeutics Accelerator Wellcome Trust,United Kingdom | United States of America,Americas | Europe,South-East Asia,Europe | South-East Asia | Western Pacific,,,,Thailand,Thailand | Lao People's Democratic Republic | Indonesia | United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C01835,221386/Z/20/Z,Africa CDC Response to COVID-19,"The African Union, Africa CDC, in collaboration with WHO on Febraury 22nd, 2020 convened an emergency meeting of all 55 ministers of health to discuss the COVID-19 pandemic. At the end of the meeting, they agreed on a continent-wide strategy for COVID-19 that will allow for greater coordination, collaboration, cooperation and communication. The strategy focuses on six major technical areas and is implemented through and endorsed Africa Coronavirus Task Force (AFCOR). As of 15 March 2020, over 26 countries have reported greater than 250 cases. In Africa, the primary strategy for COVID-19, therefore, is based on limiting transmission and minimizing harm. Delaying and diminishing the peak of outbreaks can help health systems better manage the surge of patients and communities better adapt to the disruption of social, cultural, and economic activities. In order to compliment WHO's efforts to respond to COVID-19, Africa CDC is uniquely positioned to support Member States through its presence within the African Union, the highest political body in Africa, and its five Regional Collaborating Centers. The primary challenge now is executing these tactics in a continent that is large, diverse, and at high risk of social and economic disruption from a pandemic.",2020,2021,Institut Pasteur de Dakar,2620000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Africa,Unspecified,,,,Senegal,,Health Systems Research,Health leadership and governance,2020 +C01836,221407/Z/20/Z,"Western Kenya integrated COVID19 response leveraging community health strategy, youth and technology to flatten the curve and improve COVID19 case detection, isolation and management in Western Kenya","Global COVID19 infections have risen to close to 2 million with epicenters in Asia, Europe, and the USA. Africa was initially spared; however, this is changing rapidly. As of 12/4/20, 52 of the 54 African states have declared cases of COVID19, with a total of 13'814 cases and 747 deaths. Given the high prevalence of endemic diseases, chronic conflict, and fragile health systems, the potential devastation is immense. However, with early action, going big, fast, and focusing on community interventions, Africa can change its COVID19 trajectory. As of 12/4/20, Kenya reported a total of 197 cases with 7 deaths. Infections are moving towards Western Kenya. Siaya reported its first COVID19 related death on 12/4/20. Testing kits remain scarce, and the region has a total of 12 ICU beds. The status quo would lead to 70% of the population being infected with COVID19, 5% would require ventilatory support (25'000 patients in Kisumu and 35'000 patients in Siaya), overwhelming the health system. We will implement aggressive containment & prevention measures leveraging community health workers, youth, and technology and optimizing the care of patients with an integrated COVID19 response; to save lives",2020,2020,Surgical Systems Research Group,462993.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Africa,,,,Kenya,Kenya,"Policies for public health, disease control & community resilience",Community engagement,2020 +C01837,221400/Z/20/Z,COVID-Minds: Mental Health during Covid-19,"This proposal is for the establishment of an international mental health research network for Covid-19 and the running of a UK mixed-methods mental health study. The proposed network will have three core aims: To support the establishment of high-quality longitudinal studies in countries internationally exploring the effects of Covid-19 on mental health To enable international collaboration in longitudinal data analysis to understand cross-cultural differences in the mental health effects of Covid-19 To catalogue and disseminate other quantitative and qualitative mental health research on Covid-19 We will also lead a large-scale UK concurrent mixed methods study comprising a longitudinal study and a qualitative interview study to provide high quality, rigorous scientific data on the mental health impact of Covid-19 in the UK. This study is already underway and has 5 core aims: To understand the psychological and social impact of Covid-19 To map how the psychosocial impact evolves over time as social isolation measures get stricter and once measures are relaxed To ascertain which groups are at greatest risk of adverse effects on their mental health To explore the interaction between psychosocial impact and adherence to healthy and protective behaviours To identify activities during isolation that could buffer against adverse effects",2020,2022,University College London,539492.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C01838,221514/Z/20/Z,OX79 Coronavirus Record Linkage Project,"We propose to undertake large scale data linkage between critical and primary care for patients with severe COVID-19 disease to: • allow rapid assessment of the effects of routine medications and • Understand the detailed effects of comorbidities on outcomes. Assessing the effects of routine medications on COVID is urgent for two reasons. Firstly, some medications (for example, angiotensin converting enzyme inhibitors (ACEi), angiotension II receptor blockers (ARBs), thiazolidinediones and non-steroidal antiinflammatory drugs (NSAIDS)) have been implicated in causing severe disease. As a result patients and clinicians are unclear about whether they should be continued. Secondly, it has been suggested that some routine medications (for example corticosteroids and hydroxychloroquine) may treat or ameliorate infection. In both cases, the evidence underlying effects is limited. Detailed knowledge of how different comorbidities affect outcome once admitted to an ICU is critical to optimum intensive care practice during the course of the pandemic.",2020,2021,University of Oxford,321855.69,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C01839,221427/Z/20/Z,Covid-19: How it is changing us,"This landmark research aims to understand in real time, and longitudinally, how Covid-19 is changing people's experience of community and levels of social protection in society. It will specifically focus on the ways in which: Covid-19 is affecting and shaping the interactions between individuals in society and the effect on health, wellbeing, resilience, quality of life, and community digital is playing a role in community responses to the virus different measures to mitigate the virus changes the experience of community in a time of crisis individuals and communities relate to science, research and its role with respect to Covid-19 The aim of this project is to collect real-time information to inform policy makers and practitioners about how communities are responding to the pandemic, public health measures and other mitigation measures. It will also generate early insight into the potential longer-term impacts on both individuals' mental health and community wellbeing. To understand how communities are experiencing Covid-19 across the UK, we will conduct a quantitative study with a nationally representative sample across the four nations. This will be supplemented by innovative digital ethnographic research which generates in-depth real time insight into the experiences of a diverse group of 100 adults.",2020,2020,The Young Foundation,271560.38,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Digital Health | Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Policy research and interventions | Social impacts,2020 +C01840,220764/Z/20/Z,Detecting and Excluding COVID-19 at Point of Need,"Rapid diagnostics have been identified by the WHO R&D Blueprint as a critical unmet need for the control of COVID-19 - particularly in the absence of a vaccine and proven antiviral agents. Our primary objective is to develop a low cost, high performance rapid test for the detection and exclusion of SARS-CoV-2, the causative virus of coronavirus disease 2019 (COVID-19). The technology will be made available in line with the Global Access Policy for Gavi-eligible countries that are most vulnerable to onward transmission of COVID-19 and of limited detection due to insufficient laboratory capacity. The RDT will be appropriate for assembly and manufacture with multiple quality-assured partners to meet demand.",2020,2021,Mologic,1163416.24,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Wellcome Trust",United Kingdom,Europe,Europe,Africa | Europe | Western Pacific,Innovation,,,United Kingdom,United Kingdom | Senegal | Malaysia,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C01842,221556/Z/20/Z,COVER,"With the rapid development of candidate vaccines for COVID-19, this project will identify and provide guidance on a range ethical issues arising in the development and deployment of COVID-19 vaccines. Over the next six months, the COVER project will concentrate on the ethics of vaccine research and development-including phase 3 trial design and equitable inclusion of special populations in the research agenda, with a particular focus on pregnant women as well as population groups that have or likely will experience disproportionate burden from COVID-19. This project will also conduct formative landscaping work on the ethical challenges and tradeoffs in the allocation and deployment of vaccines, both globally and within nations. This work will lay the groundwork for normative guidance and mathematical models to best inform policymaking once efficacious vaccines become available for wider use, with explicit consideration and assessment of how various approaches will not only impact the trajectory of the COVID-19 pandemic overall, but also how the benefits of vaccination will be fairly distributed across different population subgroups. In addition, the COVER project will begin to address ethical issues of COVID-19 vaccine development and deployment specific to Africa, with a concentrated body of work in Nigeria.",2020,2020,Johns Hopkins University,245798,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Africa | Americas,,,,United States of America,United States of America | Nigeria,Research to inform ethical issues | Health Systems Research,"Research to inform ethical issues in Research | Medicines, vaccines & other technologies",2020 +C01843,221575/Z/20/Z,AVID-CC Adalimumab for COVID19 in community care,"While the first wave of COVID-19 is passing, we have yet to identify effective treatments. Most treatments have been used late in the illness. There is a pressing need to identify treatments delivered in community settings that avoid hospital admission. Novel immunomodulatory treatments have a well understood safety profile but are not suitable for studies such as Principle which rely on remote assessment. Hospital at home is a developing networ; teams of consultant physicians and nurses deliver high intensity care in community settings, commonly using point of care diagnostics. This provides a suitable framework for evaluation of novel therapies. This approach has parallels with healthcare systems employed in low and middle income countries and so the results will directly inform the delivery of interventions in these settings. Multiple strands of evidence identify TNFa as an important mediator of the hyperinflammatory state that is associated with poor outcome. Early intervention with anti-TNF therapy has the potential to substantially mitigate its effects and improve outcomes. Adalimumab is an established subcutaneous anti-TNF therapy. We propose a randomised dose ranging study in community settings to establish whether it can mitigate progression to respiratory failure (requirement for oxygen, non invasive and invasive ventilation) or death.",2020,2021,University of Oxford,1959448.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation | Wellcome Trust,United Kingdom | United States of America,Americas | Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase),2020 +C02146,183942,Characterization of Broadly Neutralizing Coronavirus Spike Protein Antibodies,"The two global outbreaks of severe acute respiratory syndrome (SARS) and Middle-East respiratory syndrome (MERS) underscored the recurring threat of cross-species transmission of coronaviruses (CoVs) to humans. One of the major challenges in CoV drug development are high variation rates in the receptor binding domain (RBD) of the viral spike (S) protein, which is responsible for host receptor binding and membrane fusion. This leads to a wide host and tissue tropism and makes established antibodies (Abs) against the RBD of narrow breadth. Currently, no approved antivirals or vaccines are available for any specific human CoV and no broadly neutralizing antibodies or inhibitors are known against these pathogens. New vaccination strategies are therefore urgently needed to combat these zoonotic viruses and prevent future outbreaks. In this project, we will use high-resolution molecular imaging and computational protein design to isolate and characterize cross-reactive neutralizing Abs targeting conserved regions of SARS-CoV and MERS-CoV and use this information to guide the design of next-generation subunit vaccines against these viruses. We will utilize single-particle cryo-electron microscopy (cryo-EM) to characterize complexes between broadly neutralizing Abs and the S protein of MERS-CoV and SARS-CoV to elucidate the mechanisms of viral inhibition. We will subsequently leverage this structural information to guide the engineering of next-generation subunit vaccine candidates capable of focusing the immune response toward the epitopes identified by cryo-EM. The proposed project will yield the first broadly protecting CoV Abs, pave the way for the development of a universal CoV subunit vaccine and establish a framework for the generation of epitope-based therapeutics targeting other rapidly evolving zoonotic virus families. Keywords MERS; epitope-focused vaccine design; cryo-electron microscopy; viral fusion proteins; SARS; coronaviruses; broadly-neutralizing antibodies Hauptdisziplin Strukturforschung",2020,2021,Veesler Laboratory Department of Biochemistry University of Washington,114400,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2019 +C02149,173085,Host innate immune responses to viral RNA,"""Host innate immune responses to viral RNA""Background: Coronaviruses (CoVs) are RNA viruses that have long been known to cause severe disease in livestock and companion animals. In humans, severe and fatal respiratory diseases have been observed through the emergence of zoonotic CoVs, such as SARS-CoV and MERS-CoV. CoVs are well known to efficiently evade early innate immune responses and enzymatic functions within - and virus-host interactions at - the CoV replication/transcription complex (RTC) are key to efficiently evade early innate immune responses. Working hypothesis and aims: We hypothesize that induction of early innate immune responses to CoV heavily rely on the ability of host cell innate immune sensors to access and recognize viral RNA and that CoVs have evolved efficacious mechanisms to prevent early detection of viral RNA. We further hypothesize that these early virus-host interactions predominantly take place at the CoV RTC. In order to mechanistically understand these innate immune evasion strategies, we will ""illuminate"" the cellular environment of the CoV RTC to identify host cell factors that are required for CoV replication, and host cell factors that are targeting the CoV RTC to restrict CoV replication. The reverse genetic systems for the mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E) and well characterized recombinant mutant viruses will be used in combination with murine and human models of infection to dissect key steps and key molecules involved in early innate immune responses on the molecular level. We will furthermore employ state-of-the-art technologies involving biotin ligase-mediated proximity labeling and proteomics, CRISPR/Cas9-based functional screens, and transcriptomics in combination with ribosomal profiling to obtain a detailed mechanistic view on (i) key interactions involved in early innate immune responses, (ii) the kinetics of these interactions and (iii) the kinetics of the global host cell response under well-defined conditions. These studies will provide spatial and temporal view of basic principles of viral RNA recognition and antiviral innate immune mechanisms in different primary cell types following virus infection. Expected significance: Our proposed studies will reveal basic principles of viral RNA sensing and antiviral innate immune effector mechanisms that are highly relevant also beyond CoV infections. We expect to identify key molecules, mechanisms and pathways that promote or restrict viral replication at the site of viral RNA synthesis. This information will further our understanding on fundamental aspects of viral RNA synthesis and innate immune responses to RNA virus infection, and will facilitate the development of novel strategies to interfere with viral RNA replication during the early phase of infections. Keywords viral RNA synthesis; innate immunity; type I interferon; RNA decay; reverse genetics; viral RNA sensing; RNA virus; Coronavirus; virus replication complex Hauptdisziplin Molekularbiologie",2020,2021,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,1108800,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2017 +C02150,165076,Zoonotic transmission of coronaviruses,"Coronaviruses have received considerable attention since the emergence of SARS-CoV in China 2002/2003. SARS-CoV infection in people exemplified that coronaviruses can cross the species barrier from an animal reservoir to humans and cause severe and lethal disease in humans. The emergence of MERS-CoV in 2012 showed that zoonotic transmission of coronaviruses is not a rare event. Both viruses have close relatives in bats, and moreover, intermediate hosts, such as racoon dogs, civet cats (SARS-CoV) and dromedary camels (MERS-CoV) have been proposed to facilitate zoonotic transmission. The discovery that dromedary camels harbour MERSCoV and may act as a bridge reservoir between bats and humans provides an important paradigm for the ecology of viral emergence.Interestingly, the human coronavirus 229E (HCoV-229E; causing common cold in humans), appears to have a similar history of zoonotic transmission, since close relatives were detected in bats as well as in camelid species (alpacas and dromedary camels). While MERS-CoV has a very recent history of zoonotic transmission and differences between viruses isolated from humans and camels are rather small, camel-229E-like-CoV and HCoV-229E have alreadydiverged considerably. The aim of the proposed project is to identify and characterize critical species barriers of CoV zoonotic transmission by using the HCoV-229E system as a model. Keywords Coronaviren; Speziesbarriere; Zoonose Hauptdisziplin Strukturforschung",2020,2019,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,260010.3,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2016 +C02151,160780,Viral Plasticity Underlying Tropism And Pathogenesis/ Innate Immune Evasion Of Emerging Viruses,"During the past years, numerous novel viruses of zoonotic origin, including flavi-, corona-, and arenaviruses have emerged as causative agents of severe incurable human diseases posing important public health problems. A hallmark of emerging pathogenic human RNA viruses is their low-fidelity mechanism of replication, resulting in high mutation rates and consequent high genetic diversity. Actual RNA virus populations are therefore comprised of swarms of genetic variants with high information content referred to as quasispecies. The quasispecies nature of RNA viruses allows for rapid adaptation to dynamic environments, including changing hosts and tissues during zoonotic transmission and evading host immune responses. In our present project, we will apply cutting edge next generation sequencing (NGS) technologies for a comprehensive real-time analysis of quasispecies dynamics underlying viral plasticity of major emerging viruses in relevant experimental paradigms in vitro and in vivo. We will combine our complementary expertise on highly pathogenic coronaviruses (Thiel), neurotropic flaviviruses (Leib, Gäumann), and hemorrhagic arenaviruses (Kunz) to study the genetic basis of viral plasticity underlying the tropism and innate immune evasion. Importantly, our studies will be performed in natural target cells, such as primary human airway epithelium (HAE, Thiel), organotypic culture slices of brain tissue (OCS, Leib, Gäumann), and primary human endothelial cell cultures (Kunz). These systems recapitulate major features of living tissue in vivo, are biologically highly relevant, and provide well-controlled infection paradigms that, combined with NGS, allow us to track temporal dynamics of genetic changes in viral quasispecies as a function of virus-host cell interaction and adaptation to a changed environment. Upon spill-over into the human population, viruses are subject to strong selective pressure leading to positive selection of viral attachment proteins able to use human receptors and selection of viral proteins involved in cell interactions at later steps of the viral life cycle. Importantly, the subject of selective pressure is not the individual viral variant but the entire quasispecies population, involving complex interactions between variants. The selection of specific viral variants within a population is thus impossible to predict by biocomputational models and an experimental approach is needed. In our first aim, we will use an unbiased approach based on NGS analysis of the entire quasispecies population during passage in organotypic tissue cultures. We hypothesize that alterations in the viral quasispecies are important indicators and requirements for viral adaptation including host and target cell tropism.Innate anti-viral immunity, in particular the interferon (IFN)-I system, represents a powerful first line of defense against RNA viruses. In our second aim, we will treat organotypic tissue cultures with recombinant IFN-I in order to modulate the innate immune status of cells . We hypothesize that selection by innate immune pressure will induce changes in the viral quasispecies that will pinpoint general mechanisms of innate immune evasion. Finally, in our third aim, we will use of a wide panel of functional assays, reverse genetic systems, in vitro and in vivo systems to phenotypically analyze the most interesting virus mutants identified in aims 1 and 2, and we hypothesize that the use of primary organotypic culture systems and in vivo disease models will validate biologically relevant phenotypes present in the viral quasispecies.Using a comparative approach at the level of viral population genetics, streamlined experimental approaches and technologies (aim 4), our studies on coronaviruses, flaviviruses, and arenaviruses will reveal important commonalities and differences, allowing the definition of general principles of viral plasticity in the context of tropism and innate immune evasion. The results of our study could help to predict the risk of zoonotic transmission, adding to our preparedness. By combining cutting-edge technology with an important scientific question our project will address an unmatched problem of high relevance for the infectious disease community at large. Keywords type I interferon; Coronavirus; adaptation; quasispecies; viral plasticity; Flavivirus; innate immunity; RNA virus; Arenavirus; zoonosis Hauptdisziplin Molekularbiologie",2020,2019,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,2031205,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Coronavirus | Flaviviridae,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Pathogen morphology, shedding & natural history",2015 +C02152,158269,Replication and pathogenesis of human rhinoviruses in the context of co-infections with other respiratory viruses,"Rhinoviruses (RVs) are the most frequent cause of the common cold and can be associated with disease of enhanced severity and infection of the lower respiratory tract. Rhinoviruses co-circulate with many other respiratory viruses in human populations but how they cross-interact is poorly understood. In this project, we intend to study RV replication and pathogenesis in the context of co- and successive infections with other human pathogens like influenza virus, respiratory syncytial virus and coronavirus. The interplay with cellular innate immune response will also be investigated. Infections will be performed in reconstituted human airway epithelia, a relevant model system widely used by my host laboratory to study RV biology. This study will extend the understanding of the pathogenesis of these highly common respiratory viruses as well as their pathogenesis in the context of multiple infections. This will improve patients handling in hospital settings and may avoid the misuse of medicines/antivirals. Keywords pathogenesis; innate immunity; respiratory viruses Hauptdisziplin Medizinische Mikrobiologie",2020,2018,Universität Genf - GE Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève,254100,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2015 +C02153,149784,Host innate immune responses to viral RNA,"""Host innate immune responses to viral RNA""1. Project summaryBackground: Coronaviruses are RNA viruses of both veterinary and medical importance. The SARS-CoV epidemic 2002/2003, and the recent emergence of the novel human coronavirus EMC, exemplified the zoonotic potential of coronaviruses and their ability to seriously impact on human health. Notably, in most cell types neither high nor low pathogenic coronaviruses elicit pronounced innate immune responses, such as type-I interferons (IFNs), during the early phase of viral infection, suggesting that coronaviruses counteract sensing of viral nucleic acid. During our previous SNF-funded projects we have uncovered a link between Mda5-mediated sensing of coronaviral RNA and ribose 2'O-methylation, suggesting that RNA modifications such as 2'O-methylation provide a molecular signature for discrimination of self and non-self mRNA. More recently, by assessing a coronaviral inhibitor targeting membrane-bound RNA synthesis, we found that inhibitor-resistant viruses can efficiently replicate without inducing double-membrane vesicles (DMVs). These DMVs are a hallmark of coronavirus replication and harbor dsRNA. Therefore, these inhibitor-resistant viruses represent an excellent tool to study sensing of viral RNA and antiviral effector mechanisms under conditions where dsRNA is not shielded by DMVs but accessible to binding by host cell cytosolic RNA sensors.Working hypothesis and aims: We hypothesize that induction of innate immune responses to viral RNA and restriction of RNA virus replication is dependent on (i) modification of viral mRNA, such as 2'O-methylation, and (ii) localization of viral RNA in the host cell. Furthermore, innate immune responses and restriction of RNA virus replication appears to be very different in particular cell types, depending on which particular innate immune pathways and antiviral mechanisms dominate. The reverse genetic systems for the mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E) in combination with murine and human models of infection that are amenable to genetic modification will allow us to dissect key steps and key molecules involved in host innate immune responses on the molecular level. It will be important to analyze the molecular interactions within infected primary target cells with a particular focus on interactions between pathogen recognition receptors, antiviral effector proteins, dsRNA, and the viral replicase-transcriptase complex. To do this we will generate a number of recombinant murine and human coronaviruses that are deficient in 2'O-methylation, contain inhibitor-resistant mutations and combinations thereof. Using these novel tools we will then assess innate immune responses in primary human and murine cells in order to obtain a detailed view on kinetics and quality of innate immune responses under well-defined conditions. These studies will provide spatial and temporal view of basic principles of RNA recognition and antiviral innate immune mechanisms in different primary cell types following virus infection. Expected significance: The proposed studies will provide general insights into the biology of viral RNA sensing and antiviral effector mechanisms that are highly relevant also beyond coronavirus infections. We expect to identify key mediators of viral RNA sensing and the ""antiviral state"" that are apparently counteracted by many RNA viruses through methylation of viral mRNA and shielding of dsRNA by host cell membranes. Therefore, a better understanding of these fundamental aspects of innate immune responses to RNA virus infection will facilitate the development of novel strategies to interfere with viral RNA replication during the early phase of infections. Keywords localization of viral RNA; innate immunity; type I interferon; non-self RNA sensing; reverse genetics; RNA virus; viral RNA synthesis; Coronavirus; RNA modification Hauptdisziplin Molekularbiologie",2020,2017,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,782337.6,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics",Immunity,2014 +C02154,146546,"Organizing, Communicating, and Costing in Risk Governance: Learning Lessons from the H1N1 Pandemic","Organizing, Communicating and Costing Risk Governance: Lessons from the 2009 A H1N1 PandemicOrganization, communication and costs of governance from the story: The story of the pandemic A H1N1 of 2009 The 2009 pandemic was the first global health crisis of the 21st century to be managed under the auspices of the new international health regulations (2005). Since the early 1990s, the World Health Organization has sought to consolidate a leading position in global health crises in a context of re-emergence of certain risks and the multiplication of global health actors at its side. . The management of the H1N1 pandemic took place in a complex environment undergoing profound change in terms of international public health policy. Since 2010, state agencies and international organizations have engaged in vast experience feedback operations which have resulted in public reports, the aim of which is to better understand how the pandemic has been managed around the world. Traditionally, feedback is far from simple to conduct because many organizational cultures are characterized by a culture of blame when confronted with dysfunctions or self-reported errors. This is the reason why this momentum given by national and international public health organizations, or by national parliaments and parliamentary committees in the post-crisis period, offers a very important source of data for the analyzes of researchers as well as for public policy evaluations. The questions of risk assessment strategies from the combined point of view of organizational processes, risk communication and induced costs have never been asked in a multidisciplinary framework. In addition, these three aspects (Organizing, communicating and evaluating costs) have been the subject throughout the crisis (or have been subject to criticism) of fundamental criticism and very lively public controversies during and after the pandemic. These three angles constitute the framework of this project. This project, which analyzes the organizational responses of three countries in particular (Switzerland, the United States and Japan) in relation to the reference framework of the World Organization of health, would like/wish to demonstrate that organizational strategies for mitigation, risk communication and cost-benefit analysis are in fact very closely linked. Planning and developing organizational responses during periods of severe crisis needs to be articulated with a corresponding risk communication strategy, which itself must not only account for the intrinsic difficulties linked to planning, decision-making and organization of this type of event but also show the organization of activities that has been chosen. Likewise, this strategy must attempt to propose an economic evaluation of the costs incurred and must seek to convince and attract the support of the communities affected by the allocation of these costs. Planning and organizing, communicating and paying bills are not three sequential and independent moments in the unfolding of such a crisis. The fact that these aspects are traditionally, and also in the case of this crisis, understood separately has naturally fueled by numerous social controversies, regardless of the ""good"" decisions that may have been taken. In this project, we would like to test the following hypothesis: In a context where organizational and communication strategies as well as cost-benefit evaluations have not been integrated from the start into a comprehensive and global response, controversies, inevitable by nature, had the potential to grow and damage any transparency or mobilization efforts throughout the pandemic. Many decisions at the local and national level during the pandemic were not understood. Make sense of what happened and understand to what extent the pre-determined plans, the intense preparation, the previous health crises, the development of a hostile public, the presence of public controversies led public decision-makers and front-line actors to take certain paths rather than others, have yet to be properly investigated. It is in this context that this research must be understood. Keywords Risk communications; Organizational decision-making; Pandemic preparedness; global health; Cost-benefit Analysis; H1N1; Comparative health care systems Hauptdisziplin Soziology",2020,2017,Universität Genf - GE Département de Sociologie Faculté des Sciences de la Société Université de Genève,456271.2,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,"Policies for public health, disease control & community resilience",Evaluation of elimination strategy implementation in different contexts.,Switzerland,Switzerland,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Communication | Economic impacts | Health leadership and governance,2013 +C02155,132386,Public skepticism about emerging infectious diseases,"The goal of the planned research is to extend scientific understanding about social psychological processes in public perceptions of emerging infectious diseases (EIDs). The project aims to document a phenomenon called skepticism about EIDs. This phenomenon is a newly emerging public attitude characterized by doubts that EIDs constitute a real risk, or a perception that the degree of risk is exaggerated. A related, more extreme attitude is cynicism about EIDs, characterized by doubts about the truth of information about EID risk that is communicated to the public, as well as negative views of the intentions of institutions involved in combating EIDs. Skeptical and cynical attitudes have developed out of the public's recent experience with the avian influenza (H5N1) and H1N1 outbreaks. These attitudes are currently the most critical phenomenon to understand from a public health and social psychological point of view on EIDs, because they are both novel, undocumented, and also of great import for practical efforts to manage disease risk.Based on literature from public health, social psychology of disease and media psychology, a model is developed that conceptualizes the proximal cause of skeptical or cynical attitudes to EIDs as a perceived discrepancy between official information about EIDs and personal or shared experience. Two main moderator variables are postulated to affect the relation between a perceived discrepancy and skepticism or cynicism: trust in institutions and consumption of alternative media.The model will be tested in two studies, and interview study and a survey study. Two populations will be studied: the general public and nurses. Nurses constitute an interesting contrast case to the general public because they are health care professionals and an essential element of the public health response to disease outbreaks. Nevertheless, nurses exhibited a low rate of compliance with vaccination recommendations - a unique form of skeptical professional behavior. The interview study will involve 80 participants (40 nurses and 40 members of the general public). The surveys study will involve 800 participants (300 nurses and 500 members of the general public). The studies will be performed by 2 doctoral students in collaboration, one who will focus on nurses and the other on the general public.The planned research has important implications for understanding social psychological phenomena related to infectious diseases, as well as practical implications for communication and prevention related to infectious disease risk. The applicant and doctoral students will seek publication of results in international peer-reviewed scientific journals in the fields of social psychology and public health. Furthermore, the results of the study will be made available to interested organizations in public health, to the general public and to the media. Keywords emerging infectious diseases; social representations; trust in institutions; skepticism; public opinion; trust; cynicism; conspiracy theory; vaccination behavior Hauptdisziplin Psychologie",2020,2014,Universität Neuenburg - NE IPTO - Institut de Psychologie du Travail et des Organisations Université de Neuchâtel,368324,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience",Community engagement | Communication,2011 +C02156,132023,Dynamic public perceptions of emerging infectious diseases: A longitudinal study of the H1N1 pandemic,"In a currently funded SNSF research project, we are investigating public perceptions of emerging infectious diseases (EIDs) in the Swiss population, focusing on the origins, transmission, and protective measures related to the case of avian influenza. During the initial data collection phase of the project (a large-scale survey), the world unexpectedly experienced an outbreak of a new strain of influenza, H1N1. This outbreak was subsequently declared a pandemic by the World Health Organization (WHO), and unfolded in a much-publicized manner between May and December 2009. We seized this unique opportunity to collect additional data on H1N1. We collected or plan to collect several sets of data at different points in time. We apply for a 12-month extension of the original project to analyze and publish these additional data sets. In the proposal, we recapitulate our original research questions and show that the planned analysis of the additional H1N1 data contributes to answering those questions. We describe progress in our own current research and publications and manuscripts that have been produced. The planned research will consist of three sets of analyses. First (Study 1), we will analyze two waves of surveys (total n = 302) on perceptions of H1N1 collected in May and December 2009. Next (Study 2) we will analyze two waves of interviews (total n = 75) on perceptions of H1N1 collected in May and December 2009. Finally (Study 3), we will analyze results from a survey on H1N1 that will be conducted in March 2010 (planned n = 300). These data will allow us to study the evolution of the H1N1 pandemic from its outbreak to its aftermath using multiple methods.The planned analyses on the unprecedented H1N1 outbreak have the potential to create unique scientific knowledge about how the public perceives the salience, origins, transmission and prevention of H1N1, especially from a temporal perspective. The analyses may also augment the validity and generalizability of our avian flu results, thereby strengthening potential implications for managing the risks posed by EIDs in general. Moreover, our analyses may contribute important insights to ongoing research in social psychology of disease threat. The research group will seek publication of findings in peer-reviewed international journals in the fields of social psychology and public health. Study results will also be made available to interested organizations, the media and the public. Keywords emerging infectious diseases; pandemic influenza; social representations; threat; intergroup relations; public opinion; H1N1; lay knowledge Hauptdisziplin Psychologie",2020,2012,Universität Neuenburg - NE IPTO - Institut de Psychologie du Travail et des Organisations Université de Neuchâtel,60764,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2011 +C02157,132898,Impact of RNA modification on coronavirus-induced innate immune responses,"""Impact of RNA modification on coronavirus-induced innate immune responses""1. Project summaryBackground: Coronaviruses are RNA viruses of both veterinary and medical importance. In humans, coronavirus infections manifest usually as mild upper respiratory tract disease (common cold), however, the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV), exemplified the zoonotic potential of coronaviruses and their ability to seriously impact also on human health. Therefore, we have to extend our knowledge on critical coronavirus-host interactions and basic mechanisms of viral RNA synthesis in order to develop novel and efficacious coronavirus vaccines and inhibitors.During our previous SNF-funded projects we have identified a number of coronaviral domains and functions that critically impact on pathogenicity. The identification of the replicase-encoded non-structural protein (nsp) 1 as a major pathogenicity factor led to the development of a novel type of live attenuated vaccines based on a modified coronavirus replicase gene. Furthermore, we discovered that the inactivation of replicase gene-encoded RNA-modifying enzymes by reverse genetics resulted in highly attenuated virus mutants in vivo, whereas virus replication in cell culture was only marginally affected. These functions include the nsp14-encoded N7-methyltransferase activity, the nsp15-encoded endonuclease activity, and the nsp16-encoded 2'O-methyltransferase activity. Our preliminary data suggest that these RNA-modifying enzymes are involved in host innate immune responses and therefore represent attractive targets for antiviral intervention and for the generation of rationally designed coronavirus vaccines.Working hypothesis: We hypothesize that modification of viral mRNA, such as N7- and 2'O-methylation, impact on two fundamental cellular processes, namely (mRNA 5'-cap-dependent) protein synthesis and the detection of molecular signatures for non-self RNA recognition. The reverse genetic system for the mouse hepatitis virus (MHV) in combination with a murine model for coronavirus infection allows for the use of genetically modified virus and host strains to assess the biological consequences of RNA methylation. Furthermore, it will be important to analyze the spatial-temporal molecular interactions within infected primary target cells with a particular focus on imaging interactions between pathogen recognition receptors, antiviral effector proteins, viral RNA, and the viral replicase-transcriptase complex. These studies will increase our understanding on foreign RNA recognition by the innate arm of the immune system and control of mRNA translation under cellular stress conditions, such as virus infection.Specific aims: The first aim of the project is to perform detailed phenotypic analyses of recombinant MHV mutants that are deficient in particular RNA-modifying enzymes. These studies will be complemented by high resolution imaging analyses (aim 2) of infected cells using confocal laser and electron microscopy.Expected significance: The proposed studies on the function of viral RNA-modifying enzymes and the nature of viral RNA modifications will provide general insights into the biology of RNA sensing. Furthermore, viruses rely on the host cell's translational machinery for protein synthesis, and thus control of mRNA translation represents an important focus for virus-host interactions. Therefore, a better understanding of viral RNA-modifying enzymes will facilitate the development of novel antiviral drugs and as well as the rational design of live attenuated viral vaccines. Keywords innate immunity; RNA methylation; non-self RNA sensing; type I interferon; pathogenicity factors; reverse genetics; RNA virus; Coronavirus; mRNA; cap-structure; mRNA methylation; innate immune responses; interferon Hauptdisziplin Molekularbiologie",2020,2013,Institut für Immunbiologie Kantonsspital St. Gallen,456500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2010 +C02158,127160,Respiratory viruses: improving molecular diagnostic tools and assessment of clinical impact in lung transplant recipients,"Respiratory viruses are the most frequent cause of infections in humans and can promote seriouscomplications in immunocompromised subjects or those with chronic lung diseases. In lung transplantrecipients, the graft itself is directly exposed to these viruses and thus particularly at risk of dysfunctiononce infected. In previous studies, we have described the impact of these viruses in hospitalizedsubjects and identified unexpected complications in lung transplant recipients. These observationsand a recent pilot study have established the basis of the present multidisciplinary collaborationbetween the University Hospitals of Geneva and Lausanne. The goal is to carefully assess symptomsassociated with viral infections and to evaluate whether respiratory viruses can trigger acute rejectionand bronchiolitis obliterans, the main cause of progressive graft dysfunction and death. To achievethis goal, we will use a longitudinal clinical follow-up approach by enrolling all transplant recipients inour network together with a systematic viral screening over four winter seasons. In order to avoid anyselection bias, we have planned prescheduled screening periods that will be conducted in all cohortsubjects three times per year independent of any symptoms or clinical conditions present. In addition,subjects will be screened systematically during the first three months following transplantation andduring each acute respiratory event and bronchoalveolar lavage procedure. The virological screeningwill use an updated panel of RT-PCR assays applied systematically on upper respiratory specimensand bronchoalveolar lavage fluids when available. The diagnostic assays will be redesignedspecifically for the present project using our most recent expertise and an extensive sequencecollection. The goal here is to design assays likely to detect any divergent strains or new viral variants.This project will provide not only the epidemiological pattern of respiratory viral infections, but also adescription of the associated symptoms and lung function abnormalities. In addition, the study isdesigned to specifically assess the potential causal link between viral respiratory infections and acuteor chronic graft rejections. Another major objective will be to analyze the potential pathologicalabnormalities or specific patterns linked to viral respiratory tract infections. In summary, we willaddress the very relevant question of the short- and long-term impact of these viral infections whichhas never been studied so extensively so far. Our position at the interface between molecular virologyand clinical sciences offers the unique opportunity to correlate clinical end-points with solid virologicalfindings. We have benefited from a preliminary funding that has not only allowed us to establish thebasis of this project, but also to launch the investigation. This strategy potentiates and synergizes thepresent funding request. Keywords transplantation; viral infections; graft rejection; Rhinovirus; Respiratory virus; Lung transplant recipients; Tanzania; Cycstic Fibrosis Hauptdisziplin Innere Medizin",2020,2012,Universität Genf - GE Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève,514800,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,Other | Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2010 +C02159,122366,Dynamic public perceptions of emerging infectious diseases: A longitudinal study of avian flu,"Emerging infectious diseases have been identified by scientific and political authorities as a major threat to human survival. Such diseases include AIDS, bovine spongiform encephalopathy (BSE) and avian flu, but also exotic diseases like Ebola virus, as well as re-emerging diseases like tuberculosis. Massive and coordinated research and policy efforts have been deployed to understand biological aspects of these diseases. However, successfully containing them and limiting their impact on humans also requires scientific knowledge about how the public understands and reacts to the threat they pose. There is much less research on these issues.The planned research focuses on the case of avian flu, which has recently emerged in the public sphere as an acute threat. The risk of a pandemic (= sustained global epidemic) is now greater than ever. Thus, avian flu constitutes a timely natural case study to investigate the development of public knowledge and reactions to the threat of emerging infectious disease. We adopt a social psychological perspective based on social representations research to study public knowledge of avian flu, its determinants, its variation, and its behavioral consequences. Integrating previous survey, qualitative and experimental research on perceptions of disease, threat, and intergroup relations with social representations theory, we seek to answer four research questions. First, how is public knowledge about avian flu organized? Second, how does knowledge vary according to sociodemographic background and existing cultural belief systems? Third, how does knowledge affect relevant behavior (e.g., protection measures, consumer behavior, allocation of resources like medication, avoidance of outgroups)? An important focus is on how intergroup relations in general are affected by public knowledge about diseases. Fourth, how do relevant phenomena vary over time, in other words, how do knowledge and behavioral reactions evolve as a function of varying threat levels? This last question is particularly important, because emerging infectious diseases are, by definition, new to the public. Thus, knowledge may develop and change over time (as in the case of AIDS, for example).We explore these issues in ongoing research. We have constructed a questionnaire measuring variables related to the research questions and initiated a longitudinal study of the evolution of these variables, using the student population of French-speaking Swiss universities. There are currently three waves in the data set. The first wave (n = 520) was collected in December 2005, just after avian flu emerged as a major issue in the media. The second wave was collected six months later, in June 2006. This wave comprised 110 participants from the first wave as well as 242 new participants. The third wave was collected in June 2007. It comprised 90 participants from the first two waves as well as 299 new participants. We apply for 24 months of funding beginning October 1, 2008. We plan to conduct a longitudinal survey comprising two waves of data (n = 600 for each wave) from a sample of the general population. At each wave, we will also interview selected participants from the survey study (n = 30 each time). The interviews will yield complementary qualitative data on how public knowledge about avian flu is organized. The completed study will yield valuable data on the evolution of the Swiss public's knowledge about avian flu over several years. To our awareness, it will constitute a unique resource that can lead to new insights about how the public understands and reacts to disease-related threats in general. The data have the potential to contribute to existing theory in social psychology. Furthermore, valuable implications for public health issues (e.g., the design of disease prevention campaigns) may result from this research. We plan to seek publication of results in international peer-reviewed scientific journals in the fields of social psychology and public health. Furthermore, the results of the study will be made available to interested organizations in public health, to the general public and to the media. Keywords emerging infectious diseases; avian influenza; social representations; threat; intergroup relations Hauptdisziplin Psychologie",2020,2011,Universität Neuenburg - NE IPTO - Institut de Psychologie du Travail et des Organisations Université de Neuchâtel,214926.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other | Unspecified,,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2009 +C02160,119265,The World Health Organization's Governance of Public Health Emergencies of International Concerns: Implications for Travellers from a Human Rights Perspectiv,"Through increasing international travel, any highly contagious pathogen could precipitate a global public health emergency, affecting the fate of millions of people, the security of states and causing severe economic repercussion. The sudden outbreak of SARS exemplified this threat. Therefore, the role of travellers is decisive upon the success of global disease containment strategies. Internationally, the World Health Organization (WHO) is entrusted with the global mandate on health governance and thus adopted a revised version of the ""International Health Regulations"" (IHR) in 2005, which entered into force June 2007. This legally binding document is ground-breaking because it is applicable to situations of ""Public Health Emergencies of International Concern"" and founded upon the premise of human rights, in particular emphasizing the rights implications of travellers.The dissertation will explore this interface of global disease containment, as envisaged in the IHR under WHO policy, and its implications for travellers from a human rights perspective. The main findings will try to balance a high level of global health security and the concerns of travellers, as re-quired according to the IHR and universal human rights law, through benchmarking the human right to health. This topic opens up an entirely new chapter in both global public health as well as universal human rights law. Therefore, it is of significance not only for experts on public international and human rights law, but also for the WHO and its Member States. Keywords Global Public Health Law; WHO Governance; International Health Regulations; Travellers and Human Rights; Human Right to Health; international organizations; international state of emergency; infectious diseases; public health emergency of international concern Hauptdisziplin Rechtswissenschaften",2020,2008,Georgetown University Law Center,55797.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2007 +C02161,114599,Avian Influenza. An Anthropological Perspective on a Contemporary Crisis,"In recent years, avian influenza has gradually emerged as a topic of journalistic attention, political urgency, public anxiety, medical concern, and scientific challenge. A broadening range of policy-makers, public health officials, and scientific experts have turned their attention to the troubling prospect of an avian influenza pandemic posing unprecedented problems for the protection of life on a national and international scale. Today, the H5N1 avian influenza virus is considered in many domains of expertise a major challenge to both national security and public health.Given contemporary developments, there is a need and an opportunity for critical engagement with avian influenza as both a political and biological problem. The existing literature on avian influenza is predominantly journalistic and policy-oriented, or it is technical literature in the biological and medical sciences. In this context, my project proposes to develop a conceptually innovative and empirically grounded anthropological inquiry into the scientific, technical, political, and ethical dimensions of avian influenza. Keywords infectious diseases; avian influenza; risk; danger; precaution; preparedness; rationality Hauptdisziplin Ethnologie",2020,2007,"Deparment of Anthropology University of California, Berkeley",62782.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,Research to inform ethical issues,,2006 +C02328,AH/V008765/1,"COVID-19 CARE: Culture and the Arts, from Restriction to Enhancement: Protecting Mental Health in the Liverpool City Region","This study will assess the impact on mental health of restricted access to arts and culture in a specific city region, and track, enable and enhance the value of innovation in arts provision in mitigating associated harms. Liverpool has one of the richest concentrations of culture in the UK, boasting the largest clustering of museums and galleries outside London. Cultural capital is critical to the city region's economy, contributing c10% (Culture Liverpool,2019). The city also has a pioneering history of harnessing arts for mental health care through partnerships between culture and health providers. Building on the University of Liverpool's strong alliance with organisations across these sectors, this project brings together an interdisciplinary team of arts and mental health researchers to devise and conduct, in consultation with cultural and health bodies, two surveys. Survey 1 (online interviews) will target 20 arts organisations (10 civic institutions, 10 community arts programmes, representing 'elite' and 'popular' arts) to capture (i)the impact of COVID-19 on public access to arts provision (including those who usually access the arts through formal healthcare routes) and on audience/beneficiary change over time (legacy losses and potential gains) (ii)the success of alternative (e.g. online/digital) modes of provision by arts organisations in reaching and communicating with established and/or new audiences. Survey 2 (online questionnaire and supplementary online/telephone interviews) will target c300 arts' audiences/beneficiaries to capture (i)the impact on mental health of restricted/non-existent access to usual provision (ii)the perceived value and accessibility of alternative arts provision and the latter's impact on mental health/wellbeing.",2020,-99,University of Liverpool,211169.38,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts, +C02329,AH/V00879X/1,NHS Voices of Covid-19: Creating a national collection to document and understand the impact and legacy of a pandemic through personal testimonies,"We will develop a national collection of personal testimonies and in-depth reflections around Covid-19 that will be preserved at the British Library as a permanent public resource for informing policy and practice. This builds on the infrastructure of the NHS@70 project which has been working across the four nations of the UK, gathering testimony from patients, staff, policymakers and the public since 2017 about experiences of health and the place of the NHS in everyday life and work - nhs70.org.uk. NHS@70 has trained over 150 volunteer interviewers in oral history methodologies and collected upwards of 1000 recordings. The Covid-19 work will deliver an additional 900 oral history interview sessions capturing experiences and reflections across region, age, race, gender and class. This will create an evidence-base that produces understandings of the social significance of Covid-19. Working with stakeholders across health and the voluntary sector and using co-production methods, we will identify priority themes for rapid data analysis and develop resources to feed learning into policy and practice. Developing the collection through NHS@70 will add unique value by enabling shifts in experiences, practices and policies around health and the NHS to be interrogated through defined time periods of before, during and after Covid-19. Embedding Covid-19 in the longer history of UK health will produce richer understandings of its impacts and legacy. This distinguishes this project from others that seek to create understandings from personal testimony. Importantly, building this new study out of the NHS@70 project means that if successful, we will start work immediately.",2020,-99,The University of Manchester,1200675.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts, +C02330,AH/V008668/1,Responding to and modelling the impact of COVID-19 for Sheffields cultural ecology - a case study of impact and recovery,"COVID-19 is radically affecting Sheffield's cultural ecology. The implications appear catastrophic from surveys conducted by PI for the LEP and partners. (https://www.sheffield.ac.uk/about/city/news/cultural-sector-covid-response-survey-1.887602. National sector surveys underestimate the interconnectivity of the cultural ecology of the City, the role of place, concentrating on national economic data rather than the local recovery models required (see Florida, 2005; Scott, 2006). Disparate sectors within entertainment, creative industries, leisure, heritage are overlooked in standard business responses. Data from Sheffield City Council (SCC) demonstrate that over 47% of the city's creative businesses are ineligible for government grants/loans due to business rates models/mode of production. An immediate response is required: to collect/analyse data on economic impacts on the wider sector; to understand, respond, work with the city's cultural partners assessing how this co-produced approach will enable a robust, evidence based pathway of recovery that can be a model for other places. This project capitalises on benchmark data created through 5 reports (https://www.sheffield.ac.uk/about/city/reports) and a SWOT analysis of Sheffield's cultural ecology commissioned by the SCR/LEP (August 2019) produced by Toulmin/Marshall. The combined collected data will investigate the impact of COVID-19 on Sheffield's cultural ecology - financially, socially, creatively and the implications for the wellbeing of practitioners/audiences. It will explore organisational impacts on LA funding, critique failings in sector models, provide evidence for change, examine positive adaptations. The collaboration includes civic/cultural partners e.g. Sheffield Culture Consortium. By generating immediate and relevant research data about venues, audiences and freelancers that directly impacts on the economic recovery of the sector locally & regionally with national impact, this co-produced research will bring wide and immediate impact by creating data that will directly input into local and regional economic recovery plans, provide a series of benchmark reports for wider national bodies and create a model of best practice for Core Cities and other networks to evaluate the impact of Covid on the wider creative place ecology.",2020,2021,University of Sheffield,453022.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +C02331,AH/V008781/1,Optimising cultural provision to improve older people's wellbeing through social prescribing in the context of COVID-19: Realist review and evaluation,"In recent years, cultural institutions have supported public wellbeing (e.g. increasing offers of activities and volunteering opportunities) and can be considered 'community assets' that are central to social prescribing. Social prescribing aims to empower people to address 'non-medical' challenges (e.g. isolation, anxiety, low mood) that affect how they feel physically and psychologically. The NHS has seen the introduction of link workers, employed to work in GP practices to facilitate social prescribing by connecting people to community assets (e.g. groups, organisations, charities). This might include connections to cultural institutions, which can ameliorate social isolation and give people a focus away from their worries. The COVID-19 pandemic is affecting what the cultural sector can offer, at a time when significant mental and/or social consequences of the crisis are anticipated, especially among older people. From the outset, this population was identified as 'at risk' from the condition itself and responses to it, including extreme isolation, especially if unfamiliar with online communication. Our research will explore how cultural institutions adapt to support older people's wellbeing. This will allow us to provide recommendations on being 'referral-ready'[1] cultural institutions for social prescribing for older people in the context of the current pandemic and future ones. We will use a realist approach to explore what works, for whom, why and in what circumstances. We will synthesise existing evidence to develop a programme theory on how cultural institutions might be best mobilised and engaged to support older people's resilience during and after the pandemic. We will refine this programme theory by testing it through further data collection: interviews with older people/cultural institution staff and survey with link workers.",2020,-99,University of Oxford,333687.13,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C02332,AH/V00865X/1,Communicating the Pandemic: Improving Public Communication and Understanding,"Good communication with all sections of the population is essential to managing the COVID-19 pandemic effectively. Our study will develop evidence-based recommendations to improve the communication of the pandemic by exploring how different groups receive, understand and act upon official information about COVID-19. We will conduct weekly online surveys with a representative sample of UK adults to capture public awareness and understanding of official messages, use of information sources, and relevant attitudes, values, experiences, and behaviour. Using statistical methods to analyse the survey data, we will identify differences among groups within the population and which combination of channels and messages are likely to be most appropriate for which group. To complement our survey research, a series of online discussions with groups will be carried out to explore their needs, the information barriers they might face, and how they might be communicated with effectively in more depth. Through this combination of methods, our study will provide the strongest possible evidence-based advice regarding the communication of the pandemic and the intelligibility and effectiveness of messages for different groups. Drawing on this evidence, we will deliver feasible recommendations to the appropriate bodies on how to improve public communication related to COVID-19.",2020,2021,University of Leeds,172582.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C02333,AH/V008595/1,Combating Social Isolation through Creative and Community Engagement: COVID and beyond (Community COVID).,"The coronavirus pandemic has seen a huge increase in the availability of resources designed to inspire and connect us during lockdown. From online singing groups and art classes, to guides for engaging creatively with nature from your window, garden or local park, there are hundreds of resources designed to combat isolation and stimulate creativity at home. We want to understand how participants engage with these initiatives, such as the Get Creative campaign. We want to know the positive and negative aspects of engaging with creative resources whilst at home, and how this affects participants' lives, their health and their wellbeing. We want to know what works, how and why, so that we can make recommendations about the key ingredients for high quality resources. We will use participant feedback to generate guidance for organisations to use to help people in their communities, through for example harnessing the power of volunteers to support people who may be less able to access online resources, and we will provide guidance regarding safeguarding, facilitation and accessibility. Finally, by working with participants, providers and partners we will use the learning from this project to enable organisations to support their communities as they adapt to post-lockdown Britain.",2020,2021,University College London,269584.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement,2020 +C02334,AH/V008706/1,Infodemic: Combatting COVID-19 Conspiracy Theories,"Responding to the WHO's warning that misinformation surrounding COVID-19 constitute an 'infodemic', this project will focus on conspiracy theories as a particularly harmful kind of misinformation. Our research will lead to improved strategies for combatting the spread of conspiracy theories in the pandemic. It will use methods from digital humanities and cultural studies to map how these narratives circulate in the online environment during the crisis. We will use data scraping and network visualisation tools on a longitudinal data set extracted from social media platforms in order to identify the mechanisms, vectors and histories of transmission of coronavirus conspiracy theories. We will also employ textual analysis, digital ethnography and political economy to analyse the cultural and political contexts in which these narratives arise. By producing a series of 'snapshot' mappings of this complex online ecosystem, we will be able to analyse how conspiracist misinformation has proliferated during the course of the pandemic, which in turn will enable us to assess the effectiveness of the varying interventions by the social media platforms. We will publish our research findings in a peer-reviewed journal article and short book. In collaboration with the anti-misinformation organisation First Draft, we will communicate our results and recommendations to journalists and the general public in a 'Field Guide to the Infodemic'. Working with the campaigning charity Sense about Science and the Institute of Education, we will produce educational materials for teachers, young people and science communicators confronted with the problem of how to tackle the infodemic.",2020,2021,The University of Manchester,291298.15,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C02335,AH/V008730/1,"Social Distance, Digital Congregation: British Ritual Innovation under COVID-19","Religious rituals do work, essential social work, according to both ritual theorists and the UK government, which has recognized clergy as key workers during the COVID-19 pandemic. Funerals, weddings, birth rituals, and holiday observances are vital to people's psychological wellbeing and sense of community, especially given the sense of unease created by the pandemic. But the key means by which clergy do this vital work-live communal ritual-is not possible during lockdown conditions. And so ritual specialists have been forced to improvise means of moving rituals online, something which is virtually unknown to most mainstream clergy. Because these improvised innovations are being done quickly by busy practicing clergy with little co-ordination between them, they are not being collected or studied in a systematic or detailed way. The full implications of these innovations are thus not being adequately considered or developed in ways that could be beneficial for the wellbeing of Britons of all faiths long after the pandemic is over. This project will fill that gap. It will work with religious professionals of a range of faiths from across Britain to capture, analyse, nurture and develop these fire-forged innovations and the possibilities they facilitate, using digitally-led methods drawn from digital religion, online religion and performance studies, including involving subjects in action research. These findings will be shared broadly and accessibly for the benefit of the field. They will also contribute academically to ongoing discussions of the changing practices of religion and ritual in the era of digital culture.",2020,2021,Manchester Metropolitan University,264240.1,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C02336,AH/V008714/1,NURSING NARRATIVES - Racism and the pandemic,"This research will use storytelling as a methodology to develop our understanding of the impact of discrimination that BME nurses have experienced during the Covid19 crises. It will consider how this compares to their previous experiences of working in the NHS and their vision for a more equitable future. The project aims to collect direct testimonies from nursing and support staff to present detailed personal accounts of their experience both during the crisis and historically. The emerging discourse on the diverging impact of Covid19 by ethnicity has focused on pre-existing co-morbidities, cultural differences, possible genetics differences. While socio-economic factors have been referenced with comments on 'pre-existing inequalities in health and healthcare', there has been little address to questions of implicit and explicit racialised discriminations. It is however crucial to develop our understanding of the impact of racism. Feb 2020 BMJ special issue on Racism in Medicine highlighted continued inequalities and discrimination faced both by service users as well as staff in the NHS. Critical Race Theory suggests experiential knowledge, critical consciousness and centring research in the margins are essential strategies to further our understanding of structural inequalities. (Delgado & Stefancic 2017) Using an arts based approach that centres emotion as a resource for memory and recovery we will enable nurses to recount their experiences, visualise their traumas and those of communities worst affected by the crisis, and recognise their experience and insights as a crucial asset in creating significant change with which to support the building of a more inclusive society and a more equitable NHS capable of delivering the best patient care.",2020,2022,Sheffield Hallam University,356887.23,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C02337,MR/V027859/1,PHOSP-COVID Post-hospitalisation COVID-19 study: a national consortium to understand and improve long-term health outcomes,"The COVID-19 pandemic has tragically led to severe acute illness, hospitalisation and death. Beyond the health of those affected, it has had widespread economic, psychological and societal effects. The clinical spectrum is broad, ranging from those with no or minimal symptoms to severe pneumonia in 15-20% with evidence of widespread disease beyond the lung. As we emerge from the first wave of the pandemic we have new insights into the acute phase of this disease but very little information concerning longterm effects of COVID-19 and the ongoing medical, psychological and rehabilitation needs of these patients. We shall establish a national consortium and a research platform embedded within clinical care to understand and improve long-term outcomes for survivors following hospitalisation with COVID-19. We have built the consortium from existing expert groups across the UK and shall use standardised assessments of patients, including advanced imaging, recording of information and collection of samples. This study will provide us with a comprehensive understanding of the impact on the health of those that have been hospitalised with COVID-19. This will enable trials of new strategies of clinical care including personalised treatments to improve the long-term outcome of current and future COVID-19 survivors.",2020,2022,University of Leicester,5588908.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Post acute and long term health consequences,2020 +C02338,MR/V027506/1,The production and application of SARS-CoV-2 reverse genetic systems to facilitate vaccine development and biosafe drug discovery platform,"The development of coronavirus reverse genetic systems has been slow and limited to few laboratories worldwide. We have established a rapid approach to generate a SARSCoV-2 reverse genetic system, by targeted recombination of synthetic SARS-CoV-2 cDNA fragments in yeast, using a yeast artificial chromosome (YAC) vector. Nanopore minION sequencing was used to quickly identify correctly assembled YAC clones, that can be transcribed in vitro to produce RNA corresponding to the SARS-CoV-2 genome, which can be used to recover recombinant SARS-CoV-2 (Figure 1A). The entire process takes 2-3 weeks from the receipt of synthetic DNA. We now propose to use this reverse genetic system to develop: 1) recombinant SARS-CoV-2 reporter viruses expressing one or more reporter genes, in place of genes that are non-essential in cell culture: SARS-CoV-2 reporter viruses can be used to rapidly characterise viral infectivity and will be used to develop high-throughput virus antibody neutralisation and escape assays, to underpin viral vaccine development. 2) a biosafe SARS-CoV-2 ""replicon"" which lacks the viral structural genes but can replicate intracellularly. Human cell lines stably expressing SARS-CoV-2 replicons are powerful tools for antiviral screening and in contrast to assays with SARS-CoV-2, can be undertaken at containment level 2. These constructs will allow academic and commercial laboratories to undertake highthroughput antiviral assays, removing a bottleneck in drug discovery efforts. Furthermore, combined transcriptomics and proteomics will be used to characterise the effects of the recombinant reporter viruses and replicons on the host cell, ensuring that the engineered viruses faithfully represent the natural virus.",2020,2021,University of Bristol,134915.59,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2020 +C02339,MR/V027638/1,COVID-19: Longitudinal immunological and multi-omic profiling of haemodialysis patients,"COVID-19, caused by infection with SARS-CoV-2 ('coronavirus'), is a global emergency. Although most people suffer only mild symptoms, some people get seriously ill and the disease is deadly in around 1%. Patients with kidney disease are at high risk of developing serious illness. We urgently need new treatments for COVID-19. In order to develop them, we need to understand why some people get so ill. In these people, we think that the virus causes the body's immune system to goes into 'overdrive' and this causes collateral damage to the body. It is likely that this damage is caused by cells, genes and proteins involved in the immune response to the virus. To understand which ones are causing the problem, we have taken blood samples from patients with kidney disease who are receiving dialysis treatment 3 times a week and who have been infected with COVID-19. This means that we can look at blood samples over time to understand which genes are being switched on and which proteins are changing, particularly in patients who develop the most severe form of the disease. This will help us decide which drugs might help patients and improve survival.",2020,2021,Imperial College London,385678.41,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C02340,MR/V02776X/1,"COVID-NURSE. The development, testing and evaluation of a COVID-19 fundamental nursing care protocol: a randomised controlled trial","Background: nursing care is a key determinant of patient experience and correlated withsafety, clinical effectiveness, care quality, treatment outcomes and reduced overall serviceuse. No evidence-based nursing protocols exist to address the unique challenges ofnursing hospitalised patients with the SARS-CoV-2 virus.Aim: to co-create and evaluate the impact on patient experience, care quality, functionalability, treatment outcomes and costs of a nursing care protocol specifically addressingthe fundamental care requirements of hospitalised patients with the SARS-CoV-2 virus notinvasively ventilated.Methods: 2-stage mixed-methods programme, following revised 2020 complexinterventions guidance, of: 1) rapid-review, survey, co-creation consensus development ofa nursing protocol; 2) rapid-cycle cluster randomised controlled trial with embeddedprocess and economic evaluations.Deliverables:1.Fundamental nursing care protocol for hospitalised patients with the SARS-CoV-2 virusnot invasively ventilated, with proven effectiveness on patient experience, care quality,functional ability and treatment outcomes within 9 months of project inception.2.Feasible, acceptable and 'implementation-optimised' protocol for widespreadimplementation, through co-creation and changes implemented during rapid cycle trialwaves.3.Adaptable protocol designed to be generalisable for environments such as care homes,patients with other conditions requiring isolation and to global health systems viaknowledge gained in a process analysis of intervention fidelity, mechanisms, contextualfactors and implementation.4.Guidelines, education materials and strategies accessible via Health Education England,the Open University's FutureLearn web platform, and experienced NHS sites acting astraining hubs for other health Trusts/care homes/global health systems.",2020,2022,University of Exeter,412131.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,Clinical trials for disease management | Health service delivery,2020 +C02341,MR/V021206/1,A rapid realist review of community pharmacy support for the public health agenda during the COVID-19 pandemic and future health emergencies,"Background: Community pharmacy has a key role in the current COVID-19 pandemic; this includes mass vaccination, medication supply and providing advice. A realist review is ideally suited to making sense of complex situations such as how community pharmacy can most effectively support the challenges presented by COVID-19. This rapid realist review will use secondary data with input from key stakeholders.Aim: To understand how and when community pharmacy can effectively support the public health agenda in during pandemics such as COVID-19.Method:The realist review contains six stages to develop the programme theory:1. Focussing the research question to identify key priorities, such as supporting mass vaccination.2. Developing initial programme theory, a 'rough and ready' explanation for what needs to be done, by whom, how and why, and in what contexts.3. Developing the search strategy, to rapidly identify academic literature from relevant databases.4. Selection and appraisal of documents based on rigour and relevance.5. Data analysis/synthesis to develop and refine the programme theory.6. Data from the analysis will be used to identify: mechanisms that need to be 'triggered', and related contexts so that community pharmacy can support the public health agenda. Practice guidance, underpinned by the programme theory, will be produced.Key stakeholder input on the initial and evolving programme theory, and the guidance developed will be obtained.Dissemination: Results will be shared with patients, policy-makers and clinicians. Guidelines will be rapidly disseminated via established and evolving links with key professional bodies.",2020,2021,Aston University,56417.77,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Health Systems Research | Policies for public health, disease control & community resilience",Health service delivery | Community engagement,2020 +C02342,MC_PC_20014,"Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: the COVID-HEART study","COVID-HEART is a large UK multi-centre consortium committed to work together to answer a set of unique and important clinical questions. The bid is backed by the major UK professional cardiovascular societies and the NIHR-BHF Cardiovascular Partnership have designated it as a ""COVID-19 Cardiovascular Disease UK Flagship Project"" (see attached letter). Whilst up to 20% of hospitalised COVID-19 patients may have cardiac injury based on serum troponin (and associated with high mortality), this is non-specific and can relate to pericarditis, myocarditis, acute coronary syndromes, acute heart failure, arrhythmias, or simply hypoxia/sepsis/shock. Cardiovascular magnetic resonance (CMR) can make a specific diagnosis and is recommended in European Society of Cardiology practice guidelines. We will use CMR to determine 1) the UK prevalence of acute myocardial injury/myocarditis secondary to COVID-19 and the severity of presentation; 2) how clinical outcomes associate with recognised risk factors for mortality such as age, sex, ethnicity and comorbidities (diabetes, hypertension, heart failure, and coronary/peripheral vascular disease; 3) if there are differences in myocardial recovery at 6 months dependent on demographics, genetics and comorbidities, and how this impacts on patient quality of life and functional capacity; 4) if we can improve the ECG diagnosis of myocarditis minimising the requirement for invasive cardiac investigations. Ethics approval has been granted for clinical CMR scans enabling us to start quickly, and if funded we would extend this approval to include the additional research scans, other investigations, patient reported outcome measures and follow-up as described below.",2020,2021,Leeds Teaching Hospitals NHS trust,507687.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C02343,MR/V027409/1,Modelling the dynamics of viral load to reveal mechanisms of protection in COVID-19,"Characterising the protective host-response in COVID-19 is a critical step towards developing effective treatments and vaccines. Increasing pathogen load stimulates the host response to infection, but identifying the protective components of the response in humans is challenging in cross-sectional studies. Variation occurs between individuals in both the dynamics of pathogen load over time and the relationship between pathogen load and magnitude of the host response, and this variation can be harnessed to identify correlates of protection. A mathematical model of the relationships between pathogen load and host response can be developed using population data and then used to make quantitative estimates of the model parameters determining pathogen load for individual subjects. Importantly, we have shown that parameter estimates in individuals can then be correlated with measured host factors, to identify biological mechanisms controlling pathogen load (Georgiadou et al Nature Microbiology 2019). We propose to develop a within-host model of viral load dynamics in COVID-19 and use it to: i) quantify parameters of viral load control for individuals; ii) predict clinical outcome; iii) identify constitutive host characteristics associated with control of viral load; iv) identify components of the blood and mucosal immune responses which control viral load. We build on extensive clinical and biological data generated by NIHR priority studies ISARIC-4C and DIAMONDS, adding value to these projects and expediting their public health impact. Our approach will deliver a prioritized list of host factors which control viral load dynamics, underpinning development of more effective, and potentially personalised, treatment and vaccine strategies.",2020,2021,Imperial College London,128463.84,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease models | Disease pathogenesis,2020 +C02344,NIHR132154,Exploratory assessment of the key drivers of cost-effectiveness of tests used in the COVID-19 pandemic,"The focus of this project is to undertake exploratory economic modelling of hypothetical SARS-CoV-2 viral detection point-of-care (POC) tests and serology tests, to identify the parameters that are most influential on cost-effectiveness modelling results. The assessment will include modelling of the Medicines and Healthcare products Regulatory Agency's (MHRA) target product profiles (TPP) rather than particular tests, which will allow the utility of various use cases to be explored. The TPPs outline the desired profile or characteristics of the COVID-19 tests. This assessment should help inform DHSC's, NHS England and NHS Improvement's COVID-19 diagnostic strategy, and the need for further research or audit commissioning on key data that are missing or found to be highly uncertain. The assessment will provide a framework to enable accelerated evaluation of such tests in the future for guidance development.",2020,2020,The University of Sheffield,128953.13,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C02345,NIHR132546,Learning from COVID-19 related trial adaptations to inform efficient trial design - a sequential mixed methods study,"Abstract: Background: Activities related to clinical trials (recruitment of participants, delivery of the intervention and follow up appointments) are often undertaken in person. Many such activities, such as measuring blood pressure, or prescribing medications, are difficult to undertake remotely. COVID-19 related social distancing has meant that in order to continue, clinical trials are having to adapt the way they undertake trial procedures. This situation provides an opportunity to investigate new ways of undertaking clinical trials that may improve the efficiency of trials after the pandemic. Aims of the research: The aim of the project is to identify the adaptations CTUs are making in order to incorporate COVID-19 related social distancing and identify those adaptations that may improve the efficiency of trials after the pandemic. Design and methods: The study will be undertaken in 3 stages. Firstly, a survey will be distributed to all CTUs to identify the changes that have been made to trials. Secondly, 6 trials will be selected for further investigation. Those staff involved in the selected studies will be interviewed in order to discuss the changes that have been made and the lessons learnt. Lastly, at the end of the project a workshop will be held with those involved in the clinical trials (both patient representatives, clinicians and academics) in order to develop guidance which will detail adaptations that can be made to trials in order to improve their efficiency. Patient and public involvement: PPI members will be identified from individuals who are already providing PPI input into the selected studies. PPI representatives will be invited to attend the workshop, where their input will be sought into the guidance. Dissemination: The guidance document will be distributed to all registered CTUs in the UK, and will be published in a journal in order to achieve wider dissemination.",2020,2021,The University of Sheffield,104746.29,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel | Nurses and Nursing Staff | Physicians | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Therapeutic trial design | Vaccine trial design and infrastructure,2020 +C02346,NIHR132703,A mixed methods evaluation of remote home monitoring models during the COVID-19 pandemic in the UK,"Delays in the escalation of patient cases during the COVID-19 pandemic has led to the admittance of patients with advanced course of the disease, requiring invasive treatment and potential admission to ICU. Remote home monitoring models (sometimes referred to as 'virtual wards') seek to remotely monitor patients considered high-risk of deterioration at home to: 1) avoid unnecessary hospital admissions (appropriate care at the appropriate place), and 2) escalate cases of deterioration at an earlier stage to avoid invasive ventilation and ICU admission. Remote home monitoring models have been implemented in the US, Australia, Greece and UK, with some variation in the frequency of patient monitoring, modality (telephone or video calls and use of applications or online portals), patient criteria and use of pulse oximetry (Margolius et al. 2020; Karampela et al. 2020; Thornton 2020; Hutchings et al. 2020; Kricke et al. 2020; Annis et al. 2020; O'Keefe et al. 2020; Ford et al. 2020). In the UK, at least 10 remote home monitoring models have been documented with the aim outlined above (this does not include models operating as a step-down service following hospital inpatient stay). These models have mainly involved the following processes: 1) patient triage through 111, GP practice, hot hub (or ED for those pilots in secondary care), 2) patient provided with pulse oximeter, patient information (including escalation warning signs and what to do) and mechanism for recording observations regularly (app or paper diary) (potential observations being symptoms, pulse, heart rate, temperature, O2)., 3) patient receives regular monitoring calls from staff (either primary or secondary care depending on pilot). Symptoms and trends of O2 saturations are monitored. Modality/frequency of surveillance at clinician discretion. Calls are used to identify cases of deterioration and inform patient of next steps, and 4) Patients expected to 'check out' around 14 days mark (when recovery expected) - follow up to check symptoms and have oximeter and diary returned. Despite previous research on the use of remote home monitoring models for other conditions, there is a lack of studies on the implementation of these models for remote home monitoring during the COVID-19 pandemic. This mixed-methods evaluation of remote home monitoring models in the UK will seek to address this gap in two phases: (i) by capturing the lessons learnt during the implementation of these models during wave 1 of the pandemic and (ii) evaluating the implementation of the models during wave 2. The protocol has been developed during a four-week scoping exercise which has included initial scope of the literature (see appendix 2), discussions with each of the proposed sites (n=11), documentary analysis, and discussions with colleagues at PHE and NHSE. From discussions with a team from Imperial, our understanding is that they will be analysing retrospective data from sites operating during wave 1 of the pandemic provided to them by NHS Digital; therefore we are not proposing a quantitative analysis of outcomes in phase 1.",2020,2022,University College London,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C02347,NIHR132679,Pre-hospital specialist triage of potential stroke patients using digital technology: a rapid service evaluation to capture learning and impact of innovations prompted by the COVID19 pandemic,"Stroke is a major cause of death and disability, in the UK and internationally. Evidence from urban settings suggests that centralising stroke systems into a small number of hyper acute stroke units (HASUs, which offer rapid access to stroke specialist assessment and treatment, including clot-busting therapies if appropriate) is linked with better care delivery and outcomes.Such systems rely on effective collaboration between multiple stakeholders, including hospital stroke services and ambulance services, to ensure appropriate transfer of patients to HASU. The NHS Long Term Plan reinforces the role of networked stroke systems at regional level to improve care delivery and clinical outcomes. Integrated Stroke Delivery Networks (ISDNs) are made up of multiple health agencies, including ambulance Trusts, and aim to ensure that NHS stroke services comply with seven-day quality standards for stroke care and National Clinical Guidelines for Stroke. In addition, there is support at the highest level of the NHS to scale up technologies that improve the quality of stroke services, such as through the potential use of artificial intelligence to interpret CT and MRI scans and the implementation of telehealth. Digital technologies have potential to support more effective stroke care systems, such as at the pre-hospitalisation triage stage, through the utilisation of mobile devices or telemedicine that connects clinicians to patients remotely. For example, because of limited specificity of screening tools for stroke (e.g. FAST), acute stroke services commonly manage large numbers of potential stroke patients who turn out to have different conditions (so-called 'mimics').[10] Specialist stroke assessment via telemedicine has been found to support accurate triage of patients and has potential to identify patients who do not need urgent treatment in a specialist unit. However, to date, the piloting and implementation of such technologies has been limited in England. Reported obstacles to adoption include technical issues (e.g. reliable video-signals), and cultural barriers (e.g. anecdotally, paramedics' unwillingness to reach out for advice of this kind from stroke consultants)",2020,2020,University College London,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2020 +C02350,NIHR131931,Developing a Public Health Research System to Support Local Government in Kent,"This project will build the foundations of a system across the county of Kent that promotes knowledge mobilisation and research activity particularly in relation to the wider determinants of health. This may promote better decision-making and use of public funds. This work is timely, as during the recovery phase from the COVID-19 pandemic, it is particularly important to inform the prioritisation agenda. We will study two councils, Kent County Council and Medway Council. Kent County Council serves 1.5 million people across a largely rural area with several large towns. It is an upper tier authority with 12 districts. Medway Council is a unitary authority serving about 280,000 people in the north of the county, made up of a large coastal conurbation and surrounding rural area. They are linked, in health terms, by a joint Health and Wellbeing Board, a single Sustainability and Transformation Partnership and a single clinical commissioning group and have access to the same NIHR infrastructure and university resources. We envisage that we will gain informative insights from including two closely linked but differently structured councils, and ultimately an efficient research system will cover both given the shared geographies and academic links. The evidence suggests that the process of policy decision-making in local government uses research evidence less than the NHS, giving greater emphasis to local context and political constraints. There may be less recognition that research evidence can support better, more rational decision-making and better value. Public health departments in both councils use research evidence and are involved in research, but it is likely that systems to facilitate research activity could be strengthened, especially across the full range of local government functions that have an impact on health (e.g. strategic planning, transport, economic development, housing, leisure, environmental health, green spaces). We plan to carry out a survey of local government officers across the county to understand the extent to which research is used or commissioned to inform decision-making, what perceptions and attitudes are to research, and what is knowledge of research and resources available. We will then carry out interviews with informants including officers and elected members, to gain an understanding of what needs to be in place to promote use of research evidence and greater involvement in research. We will then bring together council representatives, academics and other stakeholders (including members of the public) in a workshop to develop a logic model and plan for the structure and function of a research system and what is needed to implement it. We aspire for the findings to be used to develop a costed implementation plan for the Kent research system. The learning will be shared across the NIHR Applied Research Collaboration for Kent, Surrey and Sussex to encourage similar approaches in other parts of the region and nationally.",2020,2020,University of Kent,63412.38,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Other,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health leadership and governance,2020 +C02351,NIHR131566,Public Health Intervention Responsive Studies Team,"Our team brings many years of experience in applied translational research in public health across three nations of the UK: Fuse Centre for Translational Research in Public Health in North East England; the School of Health and Related Research (ScHARR) at Sheffield; the Centre of Excellence for Public Health in Northern Ireland; the Scottish Collaboration for Public Health Research and Policy and the MRC/CSO Social & Public Health Sciences Unit. Hosted by Fuse, we build on its existing expertise from the innovative rapid response and evaluation service AskFuse service and UK wide links to other NIHR infrastructures and draw on experience with the national Public Health Practice Evaluation Scheme (PHPES), a response mode funded evaluation programme operated by SPHR. We are complementing both schemes by building capacity in responsive research with researchers and knowledge brokers across jurisdictions that enables a rapid response to the research and evidence needs of local government (LG). Our team combines expertise in local and national policy making from across the UK and, while members are located in the north of the UK, our networks cover the whole UK and we will draw on capacity within these networks. We understand the challenges LG faces in mobilising research evidence in a climate of austerity and within a political organisation that requires a range of different types of evidence and research designs to provide local policy makers and practitioners with knowledge that is timely, relevant and useful to ensure interventions work in their local context. The challenges facing LG will be made more acute by the current COVID-19 pandemic, the implications for which will be profound to LG and the communities they serve, particularly in terms of health inequalities. We value co-production as a core mechanism for creating meaningful relationships and knowledge to mobilise and implement evidence to address the most important research questions facing partner organisations. We have extensive experience of working with public health partners to co-produce research and translate high quality research findings into relevant, timely and useful outputs to inform decision-making in LG, build capacity and upskill staff. We will also draw on our experience and that of the LG partners to ensure meaningful public and community involvement in all aspects of our work, following the NIHR SPHR Public Involvement and Engagement strategy. Our model of approach follows a 5-step process: brokerage, work allocation, research, reporting & knowledge mobilisation (KM), and continuous improvement, which includes Evaluability Assessment methodology and embedded research with LG practitioners. With a track record in translational research, wide-ranging methodological expertise and with extensive networks with LG across the UK, we will be able to respond quickly and tailor research to local needs in collaboration with policy makers and stakeholders. Effective dissemination and KM is critical in ensuring impact. We will draw on our experience, applying the NIHR SPHR six knowledge sharing principles, in innovative ways to disseminate and mobilise our research findings into policy and practice, working with LG and the public, and tailoring outputs to relevant audiences, including Government, policy, practice and the public. We will maximise impact by collaborating with the other response teams to align projects and facilitate programme evaluation.",2020,2023,University of Newcastle,1940774.83,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Community engagement | Cross-cutting,2020 +C02352,COV19\200446,Ethical advice and ethics committees in the pandemic,"The research will conduct an evaluation of the role of ethics committees in the pandemic. Committees operate at the national level - both as part of Government and in relevant professional organizations - and at the local clinical level. They produce guidance supported by statements of general principles raising questions as to the origin, status, value, relevance and timeliness of guidance and its potential to conflict. The research will evaluate the guidance and offer recommendations as to the best and most appropriate role of the ethics committees interpreting, supporting and implementing that guidance.",2020,-99,"Queen's University Belfast, School of History, Anthropology, Philosophy and Politics",12486.92,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues in Research | Health leadership and governance, +C02353,COV19\200709,The Consequences of Covid-19 on Mental Health and Political Attitudes,"Life changes due to Coronavirus/Covid-19 responses are predicted to have serious implications for people's mental health, as warned by the WHO and other experts. Given the alarming rates of common mental disorders like depression, anxiety, and stress, the Covid-19 pandemic is likely to exacerbate these already high prevalence rates. With an imminent coronavirus economic recession, these rates are unlikely to improve. These changes in mental health may have important implications for political efficacy and political support, which are closely connected to governments' responses to the pandemic. This project addresses these issues through the use of survey research in the UK. By identifying emotional functioning as a key source of political inequality, our research is original and interdisciplinary and is important for tackling stigma associated with mental illness and for better understanding the relation between mental health and political attitudes.",2020,-99,"University of Liverpool, Department of Politics",13100,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C02354,COV19\200056,Reshaping relations between the state and the private sector post-COVID-19?,"Measures adopted to slow the spread of COVID-19 have inflicted deep and precipitous damage on the global economy. Governments across the world have had to massively increase their borrowing to try to mitigate this unprecedented financial shock, hoping to prop up viable but illiquid firms for the duration of the lockdown and to see a swift re-starting of private sector activity once restrictions are lifted. This unprecedented reshaping of the relationship between the private sector and the state, with governments stepping in as buyer and lender of last resort, means new oversight mechanisms are urgently needed. Society needs mechanisms via which it can assess and, if necessary, redress, moves by firms which have taken state aid. This project will explore the feasibility of adopting a 'social licence framework', based on the Enlightenment thesis of 'doux commerce' and social contract theory, and make recommendations for regulatory changes.",2020,-99,"Reading Centre for Cognition Research, University of Reading, UK, Department of Philosophy",11919.64,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C02355,COV19\200918,"Policing a pandemic: An exploration of police use of powers during COVID-19, dis-proportionality and the impact on public perceptions of police legitimacy.","Traditional UK policing relies on Peelian principles of policing by consent in which public views of police legitimacy are based on transparency about their powers, integrity in exercising powers and accountability for doing so. This research seeks to explore the impact of the Coronavirus Act 2020 on public perceptions towards the police and examine their use of powers. This project seeks to explore these issues within the force area of Merseyside specifically, but hopes to serve as a catalyst for further examination of these trends nationwide and internationally. A mixed methods approach will be taken via three studies: (i) an online survey exploring public perceptions of The Coronavirus Act 2020 police use of powers, (ii) an online survey examining frontline police officer experiences of the implementation of these powers, and (iii) an analysis of the COVID related arrests/use of COVID related powers in Merseyside.",2020,-99,"Liverpool John Moores University, Liverpool Centre for Advanced Policing: School of Justice Studies",12763.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02356,COV19\201444,Childhood heroes: storytelling survival strategies and role models of resilience to Covid-19 in the UK,"The generation-defining disruption to children's lives caused by Covid-19 has heightened reported anxiety levels among UK children, alongside fears for widened attainment gaps and exacerbation of inequalities. In response, public narratives have turned to storytelling, including rethinking concepts of heroism and resilience. However, these stories, along with online home-schooling resources, are fragmented and undocumented. Children's own voices also risk being lost. This project aims to mitigate educational, social and mental health impacts of Covid-19, and the marginalisation of children's voices, by 1) undertaking research into historical children's interaction with classical role-models in early magazines which forged new communities through distanced learning and 2) creative responses to heroic narratives in light of Covid-19. Collaboration with a children's magazine offers new insights into remote reading communities, creates an archive of creative responses for future research, and produces print and digital resources exploiting historical survival narratives to transform present experiences through playful pedagogy.",2020,-99,"Queen Mary Unviersity of London, School of Languages, Linguistics and Film",13100,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C02357,COV19\200837,Communicating through COVID-19 and beyond: a multi-language study of speech perception in adverse listening conditions,"COVID-19 has reshaped speech communication dramatically. Face-to-face communication now often includes one or both parties sporting a (face) mask: the listener's comprehension effort now involves mask-imposed distortions to the acoustic speech signal and a deprivation of visual cues. Online teleconferencing presents unique challenges: people often communicate from non-ideal physical spaces (echoes, background noise) and/or network set-ups (transmission delays). An increase in international collaboration means many people are not communicating in their native language. Using a multi-language study of speech perception in adverse listening conditions, we will investigate language-specific variation in adaptation performance to mask-distorted speech, speech embedded in noise, and comprehension in a second language. By better understanding the way individuals are adapting to the challenging listening experience, we will be able to inform communication guidance for a broad range of stakeholders to ensure information can be passed on efficiently and effectively, especially in remote settings, during COVID-19 and beyond.",2020,-99,"University of Essex, Language and Linguistics",13095.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02358,COV19\200422,Learning to Live with Risk and Responsibility: Understanding Popular Responses to COVID-19,"During the COVID-19 pandemic, British citizens have been asked to act responsibly in novel ways because of the risks their behaviour poses to others and their role in complex chains of causation. This project investigates how citizens have responded to these demands, aiming to advance conceptual and empirical understandings of popular responses to the pandemic. Making use of data collected by Mass Observation, the research will develop a better understanding of how people interpreted demands to act responsibly and translated them into practices of everyday life. Expected outputs include publications on how government public health communications and associated news coverage problematized the daily routines of citizens during the pandemic, and how citizens responded to these publicly circulated imperatives to act responsibly. A research workshop is planned in partnership with Mass Observation to explore how the Archive's collections can be most effectively used to advance understandings of popular responses to COVID-19.",2020,-99,"University of Southampton, School of Geography and Environmental Science",9914.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C02359,COV19\201351,Cultural policy during and after the pandemic: international insights into the recovery of the performing arts sector,"Before Covid-19, the cultural sector was already in crisis - precarious labour conditions, intersectional inequalities and insufficient public funding, particularly but not exclusively in the global South. Now, performing artists have been hit hardest due to venue closures, restrictions in public space and the fact that many cannot perform to digital audiences. While public emergency funding helps cultural workers and arts organisations, its scope and impact vary internationally across socio-economic and institutional contexts as well as different approaches to lockdown. Through in-depth interviews, focus groups and policy workshops with performing artists in the UK and Argentina, together with secondary analysis of ongoing surveys, the project will examine how the pandemic is affecting cultural workers from a sociological perspective. By discussing the work strategies that 80 musicians, actors, dancers and circus artists are now deploying, suggestions will be made about how cultural policy can best support the recovery of the sector.",2020,-99,Goldsmiths University of London - Institute for Creative and Cultural Entrepreneurship,13041.05,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom,Argentina | United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02360,COV19\200122,The two 'Big C's': Colorectal cancer diagnosis during the COVID-19 pandemic,"Cancer is a leading cause of death in the UK. Public health approaches to cancer control are framed around cancer risk, and individual responsibility to manage these risks. Recently a new 'big C' risk has emerged - COVID-19 - which, overnight, changed the way people engage with health services. Cancer diagnostic tests and treatments have been suspended or postponed. 75% fewer people are currently awaiting help for suspected cancer symptoms, with many unwilling to attend for investigation, and 18,000 excess cancer deaths are expected in the next year. Endoscopy services, through which most colorectal cancers are diagnosed, are currently at 5% of pre-pandemic provision. This interview study will seek to understand how changes in service provision and shifting social concepts of cancer/COVID-19 risk have shaped patients' experiences of a colorectal cancer diagnosis amidst the pandemic and identify what needs to, and can be, done to support these, and future, patients.",2020,-99,"Newcastle University, Population Health Sciences Institute",12743.86,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C02361,COV19\201569,Making-Unmaking-Remaking Home in Lockdown Margate,"Set in Dalby Square and Gardens, Margate, a vulnerable community disproportionately impacted by Covid-19, this project explores and maps home as process and network in a COVID 19 context using a transdisciplinary methodology drawing on law, history, architecture, health and housing studies. In this project home is understood as simultaneously bounded and networked, a space and a set of processes and relationships. We utilize the focus on home networking and home making-unmaking-remaking that has been the inevitable consequence of 'lockdown' to unpack the taken-for-granted understanding of home as a safe haven and explore issues around social and environmental regulation, inequalities, marginalization, vulnerability and dislocation as they have been intensified by COVID-19. We situate these in, somewhat paradoxical, historical understandings of Margate as a 'haven of health', and develop a toolkit for a rich and productive understanding of contemporary home making, unmaking and remaking during a global pandemic.",2020,-99,"University of Kent, Kent School of Architecture and Planning",13003.54,Human Populations,Unspecified,Unspecified,Suburban Population/Setting | Urban Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions", +C02362,COV19\200330,"Refugee-led initiatives at the time of COVID-19: exploring new forms of digital information, assistance and livelihood","ICTs are reshaping our lives not only under normal circumstances, but increasingly so in crises. The virus does not discriminate by race, gender or status but not everyone has been impacted in the same way by the crisis; migrant and refugee communities living in cities have been disproportionally affected. Within refugee studies, little research explores refugees' livelihoods, well-being, and support in relation to digitalisation. This leaves a gap in multiple agendas for refugees that risks leaving them further behind at the time of COVID-19. In this small research project we explore the existence of, potential for, and barriers to digital information, assistance and livelihood through a further under-researched phenomenon: the support provided to refugees through initiatives and organisations led by refugees. This research project aims to better understand the impact of the pandemic on new digitally mediated support in three cities: London, Berlin, and Nairobi.",2020,-99,University of Oxford - Oxford Department of International Development,13034.5,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Africa | Europe,Digital Health,,,United Kingdom,United Kingdom | Germany | Kenya,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02363,COV19\201601,"The short- and medium-term impact of the COVID-19 pandemic on exports: a firm-level comparison study in the UK, China and Germany","Globalisation and exports have been key drivers of economic development over the last decades. However, COVID-19 and associated public health policies have led to demand and supply-side shocks, which severely impact the long-running trend of increasing global economic integration. On the other hand, governments are developing special policies to encourage continued exporting. In this research, I am looking at two related research questions: 1) what is the causal impact that COVID-19 has on export performance and 2) do government export stimulus policies lead to better export performance. To study these questions, I am planning to access firm-level data from three leading exporting countries with differing policy responses to the pandemic: China, Germany and the UK and to apply econometric modelling, which I used in previous research, in order to identify causal effects. The econometric work will be complemented by interviews with a selection of 10 companies from each country.",2020,-99,King's College London - Department of International Development,13070.53,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe | Western Pacific,,,,United Kingdom,United Kingdom | Germany | China,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts, +C02364,COV19\200352,COVID-19 and reduced access to communication: the challenges experienced by deaf people,"This project will measure the impact of the lack of deaf-friendly communication strategies during the COVID-19 crisis using accessible, multilanguage online surveys. Deaf people rely on visual communication (sign language and lipreading) and struggle to read at an age appropriate level. Their access to vital information has been reduced due to the 1) lack of sign language interpreting, 2) use of face-masks and 3) use of written texts above their reading level. Furthermore, remote working increases the cognitive fatigue in deaf people because they need to look at small videos of interpreters and increase the amount of reading. We also aim to identify which of the compensatory measures to address information deficits that have originated within the Deaf community have been consulted and relied on. The findings of this research will inform future policies and we shall use them to provide guidelines for disseminating information and setting up remote working.",2020,-99,"University of Essex, Department of Psychology",13071.31,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C02365,COV19\201285,"Pandemic Times: Covid-19, Popular Mobilisation, and Socioeconomic Inequalities in Lebanon","The spread of the Covid-19 virus - and associated measures to mitigate and respond to the pandemic - is having a profound impact on patterns of inequality, marginalisation, and social exclusion. This is a particularly important challenge in many areas of the Global South, where already existing socioeconomic inequalities are likely to be intensified in the wake of the pandemic. The primary goal of this research project is to analyse how social and political movements are responding to, engaging with, and mobilising around these new socioeconomic realities. The research focuses on Lebanon, where a large wave of popular mobilisation erupted in 2019 in protest against the country's dire economic conditions, political corruption, and the crumbling state of infrastructure and public services. Utilising fieldwork in Lebanon, the research will produce an academic article and a transcription of selected interviews for a leading Middle East-related website.",2020,-99,"SOAS, University of London, Development Studies",12811.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Eastern Mediterranean,Eastern Mediterranean,,,,Lebanon,Lebanon,"Secondary impacts of disease, response & control measures",Economic impacts, +C02366,COV19\200643,"Navigating the new normal: Shifting household activity spaces in the UK, Spain and US during the COVID-19 pandemic","This research proposal builds on a recent project which solicited video tours of the homes of people during the COVID-19 pandemic. These videos give an insight into the ways that people in households around the world negotiated the radical restrictions of their activities during the initial lockdown period, and how they reconfigured their domestic spaces to accommodate functions that previously occurred outside the home. The current study aims to build on this project by shifting the focus to the ways that households are now adjusting to the relaxation of lockdown restrictions in the UK, Spain and the USA. We seek to explore the challenges of adjusting to 'the new normal'; the ways that people are orienting to the novel set of social and spatial norms that characterise this crucial transitional period of the pandemic; and the ways that household activity spaces and boundaries are now being redrawn, renegotiated, and extended.",2020,-99,Middlesex University London Department of Psychology,12603.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom,United Kingdom | United States of America | Spain,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions, +C02367,COV19\201414,The Messenger and the Message: Explaining Compliance Among the Mass Public During the COVID-19 Pandemic,"The project aims to explain the British public's compliance with and approval of government policies aimed at reducing and managing infections from the COVID-19 virus. Building on insights from behavioural and political sciences, this project examines the efficacy of messages from politicians and experts aimed at engendering compliance among the mass public. While scientists have collected survey and behavioural data on compliance, we know less about the factors that activate and sustain compliant behaviours and the role that public authorities play in shaping them. Employing nationally representative survey-experiments, we test the effect of elite cues on compliance and approval via appeals to individual and collective health risks. Moreover, we examine whether some individuals are more likely to respond to such messages than others. The project will contribute to our understanding of the public's willingness to make sustained sacrifices and the role of political and public health messages in shaping it.",2020,-99,"London School of Economics and Political Science, Department of Government",12386.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Communication | Policy research and interventions", +C02368,COV19\200862,Rethinking the ethics of vaccination,"Politicians and epidemiologists often claim that developing a Covid-19 vaccination is key to combating the pandemic. However, vaccine development and distribution raises difficult ethical questions: how certain must we be that vaccines are safe before using them in the general population? How should we choose whom to vaccinate when we can't vaccinate everyone? Should we make vaccination mandatory? As the high-profile MMR case exemplifies, these problems intersect with public vaccine hesitancy, and, therefore, public trust in science. These challenges will be even more significant in the case of a Covid-19 vaccine, which will be developed in haste, probably in short supply, and administered against a general backdrop of fear and suspicion. This project aims to use existing philosophical work on vaccination to think through the principles for ethical development and distribution of a Covid-19 vaccine, with the aim of contributing to policies which are fair, effective and trustworthy.",2020,-99,"University of Cambridge, Department of History and Philosophy of Science",12496.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures, +C02369,COV19\201517,"Solidarity in times of a pandemic: What do people do, and why? A comparative and longitudinal study","We propose a comparative study that explores how people in nine European countries react to restrictive measures introduced to contain the spread of SARS-CoV-2. We aim to gain insights into, (1) new behaviours in which people engage, (2) the motivations that underpin people's actions, and (3) how people's actions contribute to notions of solidarity. Our findings will provide a deep understanding of how the COVID-19 crisis affects people's lives in several European countries. Moreover, we will contribute to scholarship on the relationship between societal crises and solidarity. We have already carried out one wave of qualitative interviews during the time of lockdown (April 2020). Pending a positive funding decision, we will invite the same individuals for another interview six months later to obtain a longitudinal perspective. We will analyse the data using a Grounded Theory approach.",2020,-99,"Wellcome Centre for Ethics and Humanities and Ethox Centre, University of Oxford, Nuffield Department of Population Health",12608.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions", +C02370,COV19\201479,Quarantined between cultures: Overcoming communication challenges and building resilience among Chinese students residing in the UK during the COVID-19 pandemic,"This project aims to understand the communication challenges of Chinese university students studying in the UK during the COVID-19 pandemic. Chinese students comprise the UK's largest proportion of international students and are important to HEI's financial sustainability. The project will use principles from research in intercultural communication, health communication and media literacies to examine how Chinese students access and evaluate information, negotiate intercultural differences, and cope with COVID-19-related stigma, and how these processes affect their attitudes towards studying in the UK. It will adopt a participatory-research model, engaging participants in data collection/analysis, empowering them to communicate their findings to relevant parties and build resilience. The results will improve universities' ability to support international students and more broadly enhance our understanding of the problems faced by people residing in different cultures during pandemics. The unique participatory approach developed will be applicable to studying and supporting other multicultural/multilingual communities in the UK.",2020,-99,"University of Reading, Department of English Language and Applied Linguistics",13099.35,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C02371,COV19\200855,Covid-19 and Investor Stewardship: The Need for Responsible Ownership in a Time of Emergency,"Institutional investors, who control the savings of millions of ordinary people, have a key role to play in ensuring that the companies in which they invest maintain high standards of governance and accountability. Investor stewardship - the responsible allocation of capital and purposeful engagement - has particular relevance here. The global coronavirus Covid-19 pandemic - and the response to it - has impacted businesses worldwide and revealed a series of short, medium- and long-term environmental, social and governance (ESG) risks. This project will examine how the Covid-19 outbreak has impacted stewardship activities in the UK and ask questions about the social function of institutional investors and their leadership in ESG practices. This project is part of a highly innovative, longer-term and larger-scale research project on shareholder power and accountability, which can be linked to British Academy interests in ""The Future of the Corporation"" or other such funding agencies.",2020,-99,"King's College London, The Dickson Poon School of Law",13079.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02372,COV19\201225,The social and economic impact of the COVID-19 crisis on women in BAME community: a gendered analysis,"In this study we apply insights adopting Bourdieu's socio-cultural-structuralist approach to conceptualizing and identifying social and economic inequalities resulting from the COVID-19 crisis to BAME women in the UK. Drawing on empirical research with 30 women participants working in the health and care sector the study will aim to highlight the gendered impact and experiences of BAME women of the COVID -19 crisis. The findings will aim to elucidate the gendered social and economic inequalities taking into account the gendered experiences and dispositions of BAME women, including their habitus and the resultant inequalities to generate a number of implications for practice and policy.",2020,-99,"University of Manchester Alliance Manchester Business School, People Management and Organization",12942.8,Human Populations,Other,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C02373,COV19\201563,Developing effective communication about a global pandemic in a multilingual space: Language choice and language use in COVID-19 campaigns in Ghana,"This project aims to improve communication about COVID-19 in a multilingual African context. In Ghana, most COVID-19 information is communicated in English, which may restrict comprehension and efficacy. Focusing on language and using quantitative and qualitive analyses, the project evaluates the effectiveness of COVID-19 campaigns in two communities in Accra with low literacy - one monolingual, traditional and non-mobile, the other multilingual, containing female migrants from Northern Ghana. In focus groups and interviews, community members discuss their knowledge and beliefs about COVID-19 and their sources of information. This informs the development of alternative COVID-19 health promotional materials that take the linguistic and cultural characteristics of the communities into account. Their impact will be assessed in further focus groups. Findings will be presented at a workshop with stakeholders from local authorities and the Health Ministry, as well as teachers and religious leaders. A policy brief will be produced following the workshop.",2020,-99,"University of York, Department of Language and Linguistic Science",12243.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Africa,Africa,,,,Ghana,Ghana,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C02374,COV19\201043,Decentralisation of health systems and subnational variation in COVID-19 responses in OECD countries,"Existing work on policy responses to the COVID-19 pandemic has overwhelmingly concentrated on the national level, but more often than not responsibility for public health lies with the regional level of government. By wrongly attributing all authority to the national level, this ""methodological nationalism"" risks producing some misleading claims. In contrast to existing work, this project therefore analyses the divergence in regional policy responses across five OECD countries: Germany, Italy, Spain, the United Kingdom, and the United States. Divergence in responses can be the result of policies being tailored to specific regional contexts, but given the highly interdependent nature of the COVID-19 context, uncoordinated policy decisions taken might have severe negative externalities on other jurisdictions. This project seeks to find out whether divergence is the result of a lack of coordination or does whether it reflects a coordinated decision to allow divergence?",2020,-99,"King's College London, Department of Political Economy",13100,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom,Germany | Italy | Spain | United Kingdom | United States of America,"Policies for public health, disease control & community resilience",Policy research and interventions, +C02375,COV19\201483,Helping Those Who Need It Most: The Unequal Impact of COVID-19 and Policy Responses on Observed Infection Rates and Economic Status,"Macroeconomic forecasts predict a 3 to 35 percent drop in UK GDP from the COVID-19 crisis. But there has been little forecasting of how COVID-19 and the government's emergency measures will affect economic inequality, and how inequality affects the course of the epidemic. Moreover, most policies only take into account the negative economic consequences from the lockdown, while people's private fear of infection also has a direct impact on inequality between socioeconomic groups. We construct an epidemiology-economics hybrid model that captures the discrepancy between observed and true infection/mortality rates, and emphasize the disproportionate health and economic risk faced by low-wage workers and the self-employed. We differentiate voluntary from enforced social distancing, and quarantines from lockdowns. The model can predict how economic and health inequality evolve with and without government interventions, and allows for a comparison with the US and Korea, which implemented vastly different economic and public health interventions.",2020,-99,"Queen Mary University of London, School of Economics and Finance",13056.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions | Policy research and interventions, +C02376,COV19\201292,"A study of Caabuqa-Corona in the Somali Diaspora: histories of covid-19, male elders and communtiy responses in Tower Hamlets and the East End of London","Preliminary official statistics and popular perceptions suggest Covid-19 has disproportionately impacted BMAE communities in Britain. This research addresses the urgent need to respond to the likely high death rates among the Somali diaspora. It seeks to provide a detailed case-study of Somali male elders and their families in some of the poorest London boroughs, by reconstructing personal histories of Covid-19 through five phases: initial responses, illness, deaths, recovery, and moving forward - a biography of a pandemic weathered by transnational migrants. Specifically it seeks to uncover the extent of mortality and illness among male elders: what factors shaped their understanding of the disease; their responses; immediate impact; their long-term health; the role of community mobilisation; and how this experience has changed (or not) their views, behaviour and attitudes to 'home' . The aim is to provide evidence and analysis to help formulate national policies to increase pandemic resilience.",2020,-99,London School of Economics and Political Science,12188.24,Human Populations,Asian | Black,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Approaches to public health interventions | Community engagement | Indirect health impacts, +C02377,COV19\201439,"COVID and Chinese and East Asian University Students in the UK: Safety, Security, and Communication","There was a marked increase (21%) in hate crimes against East Asian communities, particularly Chinese people, in the UK in the first months of the COVID outbreak. This study is concerned with the experiences and well-being of Chinese (and those perceived to be Chinese) students. There are over 120,000 Chinese students in the UK in the current academic year. Although racist incidents are known to have taken place, our initial research finds that students are not using official channels to inform their universities. Our study aims to investigate the experiences of Chinese and East Asian students and the ways in which they communicated about racist incidents during the crisis. We will explore with whom they shared this information and how. Our findings will enable university staff and local communities to improve the strategies and practices of safety and well-being of these students.",2020,-99,"University of Manchester, Manchester Institute of Education",6209.4,Human Populations,Asian,Adults (18 and older),Urban Population/Setting,Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C02378,COV19\200092,Generosity in the time of COVID-19,"Against the backdrop of a decade of austerity measures, and in the context of a pandemic that has led to many thousands of deaths, this proposal focuses on human generosity in the UK. Generosity is one framework for understanding human giving - so important in times of crises - and our study will consider this from the rarely considered perspective of those who receive it. We see generosity as an important and productive giving practice, that occurs between people, within systems of social and economic resources. Using a range of qualitative methods (collecting stories, in-depth interviews and content analysis) our proposed research will explore: the quality, nature and experience of generosity from a receiver perspective; perceptions of the effects of generosity over time; as well as how generosity is produced within an uneven social world, paying attention to how generosity works to fill gaps left by a receding state.",2020,-99,"University of Sussex, Department of Sociology",13079.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02379,COV19\201112,The meaning of masks in the COVID-19 pandemic: a comparative study of depictions of mask-wearing in public visual arts in sub-Saharan Africa and the UK,"In an attempt to slow the spread of COVID-19, many countries have made wearing face masks mandatory in public spaces. This research explores the role of visual arts in understanding the characteristics of masks as socially imbued objects, the multiple meanings they convey, and the influences shaping how these meanings change over time. This understanding is of critical importance in informing better comprehension of the challenges related to uptake and promoting humane innovations in response to the pandemic. Drawing on a comparative study of sub-Saharan Africa and the UK, the research focuses on street and digital public art as important spaces for scrutinising public policy, discourse and debate in emergency responses to COVID-19. It employs digital ethnography, netnography, online interviews and citizen social science to document and examine depictions of mask-wearing, the cultural meanings of masks, and the significance of visual arts in public debate, community building, resilience and recovery.",2020,-99,"Durham University, Geography",13069.67,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement, +C02380,COV19\200585,"Adherence to COVID-19 public health practices in adolescence: The role of morality, group dynamics and personal choice","Adolescents face a reduced risk of severe symptoms or death from the novel coronavirus, yet there is some evidence that youth can transmit the virus at the same rate as adults. Until an evidence-based consensus is reached regarding transmission, it will be important to promote adherence to public health practices (e.g. social distancing, hand washing) among adolescents. Crucially, there is a need for research exploring how adolescents themselves reason about these issues. The proposed project will examine adolescents' reasoning about public health practices and whether this is related to behavioural intentions to engage with these practices. Second, the project will examine how misinformation can impact adolescents' reasoning and public health behavioural intentions. Together this evidence will inform the communication of COVID-19 related information in order to promote youth engagement with public health practices and challenge the potential consequences of misinformation.",2020,-99,"University of Exeter, Department of Psychology",12527.53,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C02381,COV19\200898,CityLife: Stories of Covid-19,"CityLife is a project which since 2014 pairs up writers and community elders from marginalised communities to produce literary non-fiction about life in London, and then analyses that life writing data through interdisciplinary, mostly cultural studies-based methodologies. The elder population we work with is intersectionally, socio-economically underprivileged. Under Covid-19, these people and their communities are at terrible risk and under considerable mental health strain. Funding to a new phase of the project will allow us to take this project digital, while keeping it accessible to non-internet literate people. This will reinforce our legacy of intergenerational community-building, produce new literary content and activate it in research about isolation, community and coping with Covid-19 in London. We hope that this can represent and advocate for a segment of the population currently excluded from the conversation about Covid-19 in a public engagement, academic and policymaking context and help inform future responses.",2020,-99,"University of East Anglia, School of Literature, Drama and and Creative Writing",13093.45,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C02382,COV19\200776,Raising a Child Without the Village? Social Support and Maternal Wellbeing in the Time of COVID-19,"Received wisdom holds it takes a village to raise a child. Across Western countries, the social distancing measures deployed in response to COVID-19 have significantly disrupted what remained of traditional support systems. Social support is increasingly recognised as a key determinant of postnatal health, predicting postnatal depression, mother-infant bonding, and breastfeeding outcomes. However, public health research typically focuses on partners and professional 'medicalised' support, neglecting the role of wider support and the diverse forms it takes. There is an urgent need to understand how maternal social support networks are being impacted during the COVID-19 pandemic. How social distancing is shifting access to different forms of social support will be elucidated with a UK-wide longitudinal study of mothers with young infants, and the impacts of this on postnatal depression, bonding, and breastfeeding assessed. By identifying the most beneficial network typologies we will evidence optimal targets for support interventions going forward.",2020,-99,N/A,12244.57,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions, +C02383,COV19\200057,The role of neighbourhood conditions in mental health responses to the Covid-19 lockdown,"The Covid-19 lockdown has underscored how important neighbourhoods are for our mental health and wellbeing. Neighbourhood characteristics like urbanicity, greenspace, deprivation, and social fragmentation create very different lockdown experiences, even between neighbours living streets apart. This project will investigate the role of neighbourhood conditions in mental health responses to lockdown. Data are from a longitudinal cohort of >14,000 individuals born in Bristol and surrounding areas and followed from birth for 30 years, coupled with novel data from a Covid-19 questionnaire completed by >7,500 participants. First, I will examine associations of urbanicity, greenspace, deprivation, and social fragmentation with participants' symptoms of anxiety and depression during and after lockdown. Second, I will control analyses comprehensively for confounds such as poverty using propensity score matching. Third, I will examine the interplay between neighbourhood conditions and individual-level factors including age, housing, household composition and garden access in terms of mental health responses to lockdown.",2020,-99,"University of Bristol, Population Health Sciences",11356.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts, +C02384,COV19\201476,The Nexus Between Social Capital and the Burden of COVID-19 in the United Kingdom,"This project is about understanding how social capital has shaped the spatial epidemiological outcomes of COVID-19, and establishing the elements of social capital that will be important facilitators of the socio-economic, mental and physiologic recovery of communities after the pandemic. Observed variations in the severity of the disease in the UK has rejuvenated debates about the social context of health inequalities. Using a social capital framework, this study will determine how aspects of social relationships within the social networks of communities influence the spatial patterning of the disease. The research will integrate recorded data about COVID-19 cases sourced from the Office for National Statistics, with data from the Centre for Thriving Places to explain causal relationships. Additionally, interviews will be conducted with a stratified random sample of participants across England, Wales, Scotland and Northern Ireland to project aspects of family and community social capital that will prove important for recovery.",2020,-99,"University of Lincoln, School of Geography",13080.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02385,COV19\200561,The Impact of COVID-19 on BAME Owned Businesses in the UK,"Due to the COVID-19 pandemic and lockdown, many businesses in the UK temporarily closed with the majority of businesses that operated during the lockdown doing so at a reduced capacity with lower turnover. This would have had significant implications for BAME owned businesses because they are traditionally concentrated in sectors that were particularly affected by the pandemic and lockdown such as retailing, restaurants, fast food provision, and personal services. Furthermore, research shows that BAME business owners are less likely than non-BAME business owners to engage with mainstream business support because of ethnic enclaves dominating their attitude towards institutions and government schemes, along with the absence of trust. This research will investigate the specific challenges that BAME business owners faced during the COVID-19 pandemic and lockdown, the strategies that they used to keep their businesses afloat, and how they engaged with financial and regional support.",2020,-99,"Staffordshire University, Staffordshire Business School",12377.54,Human Populations,Asian | Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C02386,COV19\200228,Finishing time at a distance: an exploration of support mechanisms for socio-economically disadvantaged and criminalised individuals during the Covid-19 crisis and beyond.,"This proposal is to conduct research with LandWorks CIO (LWC), a resettlement charity providing a supported route into employment and community for prisoners and people on community sentences (collectively called trainees), many of whom are socio-economically disadvantaged in terms of employment, housing and health indicators. Since lockdown LWC have maintained and/or re-established relationships with trainees, graduates and their families. In the absence of face-to-face contact, this research aims to map the ways individuals engage with the charity through mediums such as texts, phone calls, letters and email exchanges, with a view to developing an asset-based framework for use beyond the pandemic. The research further aims to explore the lived experience of criminalised individuals negotiating changing circumstances as a consequence of covid-19, whilst identifying some key areas of economic and social disadvantage in order to maximise mechanisms of support that could be initiated by LWC (and others) in the future.",2020,-99,"University of Plymouth, Law, Criminology & Government",13073.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts, +C02387,COV19\200127,Social Care in Times of Crisis,"The project will explore how the COVID-19 crisis is impacting the job quality of social care workers in Scotland to highlight pre-existing and new problems in the social care sector and to propose solutions. The sector has been severely affected by the pandemic but has been deemed in crisis for many years. Using the 'decent work' concept, the project will conduct interviews with key sector stakeholders - with a focus on social care workers from all care settings - and link these to existing data and research to assess job quality. The policy solutions proposed will be for the Scottish context, building on the applicants' existing research and sectoral links. However, the project will be of relevance to a UK-wide debate bolstered by unprecedented focus on care workers as 'key workers' and significant public, media and political concern on the increased personal risk and pressures they face due to COVID-19.",2020,-99,"University of the West of Scotland, School of Education & Social Sciences",12281.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C02388,COV19\200760,"Staying home, connecting care: Infrastructures and experiences of home care and voluntary support given and received at home during the UK covid 19 lockdown and beyond.","The UK covid 19 lockdown and ongoing social distancing has increased the dependence of many older people on care services provided to them in their homes. This has brought additional pressures to home (domiciliary) care provision in the social care sector and volunteer services for people at home provided by charities and non-profits, both of which were already financially stretched and operationally disconnected from each other. This research project will investigate in detail how these two strained infrastructures of care are responding to increased demand, focusing on experiences of care providers (volunteers, their coordinators, care workers and their managers) as well as care recipients who rely on both types of service. This research will inform scholarly and policy dialogues about the interface between home care and volunteer support to people at home, by considering how these separate services could be strengthened through greater cooperation.",2020,-99,"Bournemouth University, Department of Social Sciences and Social Work, in the Faculty of Health and Social Sciences.",9483.09,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Social Workers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Policy research and interventions, +C02389,COV19\201296,"Fear, Stigma and Othering: The Impact of COVID-19 rumours on marginalised population groups of Nepal","There have been rumours of returnee migrant workers from India and Muslims (who had attended religious gatherings in Nepal and India) spreading COVID-19 in Nepal. These rumours are spread and exaggerated by social media and online news portals blatantly blaming these groups as COVID-19 carriers responsible for spreading the infections into communities. We aim to explore the extent and wider impact of such mis/disinformation and rumours on returnee Nepali migrants and Muslims and establish their resilience (if any) and coping strategies. This multi-method study comprises: (a) content analysis of media contents (newspapers, online news portals, YouTube), and (b) interviews with returnee Nepali migrants, Muslims and relevant key stakeholders. Findings from this study will help develop strategies to dispel rumours and mis/disinformation targeted to these socio-economically disadvantaged/minority population groups in Nepal. We will work closely with a Nepal-based charity for field work and dissemination of this study.",2020,-99,"Bournemouth University, Health and Social Sciences",12471.2,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,South-East Asia,South-East Asia,,,,Nepal,Nepal,"Policies for public health, disease control & community resilience",Communication, +C02390,COV19\201403,When Distance is an Act of Love: Exploring the use of Video Diaries for Family Members of Intensive Care Patients.,"Due to Covid-19, intensive care (ICU) patients are not allowed visitors or have severely restricted visiting at the end of life. Most ICU patients are unconscious or extremely weak and cannot speak on a phone or video call to their family. Before these visiting restrictions, family members of ICU patients were already known to suffer significant psychological distress and now face increased distress as they are unable to visit. NHS Scotland are introducing video diaries as an emergency measure to try to support communication with families and reduce distress. The diaries may have a positive impact but there is a risk they could also have negative effects. We will explore staff and family members' experiences of using video diaries and test out using measures of distress and psychological well-being of family members. We can then make some initial recommendations and plan a larger subsequent study to test effect.",2020,-99,"University of Edinburgh, School of Health in Social Science",12721.51,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication, +C02391,COV19\201102,Twin Peaks: Covid-19 and the Labor Market,"The Covid-19 epidemic has posed significant challenges to public health. Since the virus outbreak, governments have implemented confinement measures aimed at reducing the spread of the virus. Nevertheless, these measures have potentially huge economic and social costs. Understanding costs and benefits of alternative confinement policies and supporting labour market policies is of first order. To this purpose, we build a quantitative framework that merges a search and matching model of the labour market to a standard SIR epidemiological model of contagion. Standard epidemiological frameworks abstract from modelling individual behaviour in the labor market, while standard models of labor market are not able to capture the effect of the current epidemic shock, and its heterogeneity in the population. This is the first project to fill this knowledge gap. We calibrate the model to UK data and we use it as a laboratory to evaluate welfare and distributional consequences of government policies.",2020,-99,"University of Nottingham, Economics",10571.7,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C02392,COV19\200629,"Everyday COVID-19 Art 'at home' and across borders: Community, Politics, and Resilience","Before the COVID-19 pandemic, many people's interactions with visual art had been confined to galleries or museums, touring curated exhibits of art chosen for 'us' to consume. During COVID-19, the 'museums' have gone online, and many more people and households are engaging in producing and sharing art than had before the pandemic. This project explores and curates everyday COVID-19 art with global themes, interested in its implications for global community, resilience, and everyday art/museums. It does so through the production of an online museum of the everyday, produced by a collaboration of politics scholars with an interest in art and artists with an interest in politics. It aims to produce curations and research articles focused around the visual economies of everyday art in COVID-19 times, and their meanings for cosmopolitanism and globalization in times of crisis.",2020,-99,"Royal Holloway University of London - School of Law and Social Sciences, Department of Politics and International Relations",11875.15,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02393,COV19\201055,Learning to care in unprecedented times: the impact of COVID-19 on nursing education,"Even before the COVID-19 outbreak, there was a crisis in the healthcare workforce, with 40,000 unfilled nursing vacancies. This case study of a group of final year pre-registration nursing students aims to assess the impact of the COVID-19 pandemic on this group in the midst of the emergency and the immediate aftermath, and the wider repercussions for nursing education. It will explore the students' experiences of the pandemic and inform any immediate support they may require. The project will document the short-term graduate outcomes for this cohort and their 'imagined futures', exploring the role of class, gender and 'race' in shaping their educational trajectories. In doing so it will offer vital sociological insights into the impact of the pandemic on nursing education, the support that this cohort and future nursing students may require, and the implications for addressing the workforce shortage.",2020,-99,"Manchester Metropolitan University, Sociology",10350.31,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02394,COV19\200383,Making Theatre in a Time of Covid,"This project investigates the role of performance arts at a time when conventional performance is not possible. It will use a small group of artists as a microcosm of the sector, to research what is lost when live performance cannot take place, and what the benefits to the public are of seeking new ways to recreate it in a form compatible with social distancing. The PI will work in close collaboration with a small group of theatremakers with different types of expertise. They will devise and deliver two different models of socially distanced performance, and seek feedback from an audience as to their impact and benefit. A workshop at the end of the project's lifespan will allow these models to be showcased more widely to other academics and practitioners, and will allow the sharing of good practice for how live creative work can be made in this period.",2020,-99,"The Open University, Classical Studies",11573.85,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02395,COV19\201169,LGBTQ* UK COVID-19 Lockdown Researching Young Adult Experiences Vulnerability and Resilience Over Time,"The main objectives of our programme are to assess the psychological health of LGBTQ* young adults during the COVID-19 pandemic and lockdown and to understand the pathways underlying their psychological health, vulnerability and resilience. Given the current circumstances of health anxiety and social isolation, alongside intensifying pressure on household and family relationships, a rising rate of mental health problems among LGBTQ* young adults is widely anticipated but as yet under examined. The project proposed will expand upon our newly launched online survey investigating the social support networks and psychological health among UK LGBTQ* people (aged 18- 35 years). We propose adding further follow-up survey waves (using both bespoke and standard measures) and qualitative data from an interviewed sub-sample to examine effects and pathways over time. The project develops understanding of UK LGBTQ* well-being experiences and additionally contributes internationally through comparison with equivalent data from Portugal, Italy, Brazil and Chile.",2020,-99,Birkbeck University of London - Department of Psychological Sciences,13003.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Americas | Europe,Gender,,,United Kingdom,Portugal | Italy | Brazil | Chile,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Indirect health impacts, +C02396,COV19\200891,Making it through COVID-19: the praxis of livelihood generation within craft communities of practice,"Responses to COVID-19 in the UK has seen teams of people sewing scrubs in their homes, maker-spaces fabricating 3D printed PPE masks, recreational craft providing a release from lockdown, and people enjoying the Sewing Bee on TV. Craft seems to have defined part of the pandemic experience. However, for professional makers and organisations who rely of making things for a living, COVID-19 has thrown livelihoods into disarray. Many practitioners and craft development organisations are only surviving as a result of Arts Council emergency funding or swift pivots to locate new audiences. This research dives into the professional craft community to understand the impact the disruption caused by COVID-19 has had on this industrial sector. Working with individual designer makers, long established maker collectives, high profile arts organisations and craft museums, the research will ask how (and if) the craft sector will survive in the long term.",2020,-99,"University of Exeter, Geography",13098.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C02397,COV19\201075,Mitigating the effects of national crisis: the case for a dedicated Civil Defence or Emergency Situations organisation in the United Kingdom,"The United Kingdom was found wanting when the covid-19 pandemic struck. The military had to step in to provide support. Its personnel, for instance, planned and built temporary hospitals, took over the NHS logistics system and ran the vast majority of mobile testing facilities in the country (92 out of 96). The UK government was lucky in that, almost uniquely, a large number of military personnel were available in early 2020. It may not be so lucky next time. Other European countries, though, do not rely on luck. Virtually every one of them has a standing Civil Defence or Emergency Situations body whose sole function it is to deal with sudden national emergencies. This project examines, by comparing and contrasting with other European states badly affected by the pandemic (Italy, Russia and Spain), and which utilised their Civil Defence bodies, whether the UK needs such a body of its own.",2020,-99,King's College London - Defence Studies Department School of Security Studies,12893.02,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,Italy | Russia | Spain | United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02398,COV19\201422,'We will remember them': Covid-19 and Grassroots Memorial Practices,"In March 2020, the WHO classified Covid-19-a novel coronavirus-as a pandemic. By late-May, the UK death toll had passed 35,000. The restrictions on burial rituals and closure of faith spaces may have impacted the commemoration of Covid-19 victims but the emergence of grassroots memorial practices-from yellow hearts in the windows of bereaved households to crowdfunding campaigns for local tribute events-has demonstrated the extent to which communities have adapted ceremonial processes in a period of trauma. This project will investigate these makeshift memorial activities and their post-lockdown counterparts. Data will be analysed to assess their societal role: the methods used, the groups involved and the relationship to community resilience. Alongside scholarly publications and two exhibitions, project outcomes will include the founding of The Covid-19 Memorial Archive, a digital collection of artefacts from across the UK, reflecting the scale and diversity of commemorative responses to Covid-19.",2020,-99,"Loughborough University, School of Design and Creative Arts",13077.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02399,COV19\200774,Families and Community Transitions under Covid (FACT-Covid),"This research will investigate the challenges experienced by families with children during the COVID-19 pandemic. It will explore both how individuals understand and respond to public health measures, and how these are negotiated within the family. As such, it will unpack both inter- and intra-household differences, examining how position in the household (such as that determined by gender and generation) and access to various forms of capital (such as that determined by socio-economic class), shape the ways and means through which individuals can respond to challenges in the context of a public health crisis. The study will follow participants over a year, thus examining the long-term consequences of the pandemic and the potentially changing reactions of families to public health measures. The project is part of an international network of projects, in ten different countries, led by us, all using the same methods and addressing the same questions.",2020,-99,"UCL, Department of Social Science",10584.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C02400,COV19\201302,The impact of the COVID-19 pandemic on community journalism start-ups in the UK,"This project will investigate the experience of community journalism start-ups in the UK during the Covid-19 pandemic, through 30 in-depth interviews and a survey of 100 practitioners. Community journalism start-ups - small, independently owned publications that focus on locally relevant news - are sometimes viewed as a solution to the crisis in local news provision. Their role is particularly vital in the current pandemic, where local knowledge is more crucial than ever. Yet they are highly precarious and under significant financial threat due to the pandemic's economic fallout. There is little research on these organisations, and none on their fate in the context of the pandemic. The proposed project will shed light on how the pandemic has changed the financial situation, ways of working and community relationships of these crucial news providers. The project will generate new scholarly knowledge and contribute to urgent ongoing industry and policy debates.",2020,-99,"Cardiff University, Cardiff School of Journalism, Media and Culture",13012.16,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02401,COV19\200794,Reading for Normal: Young People and Fiction in the Time of Covid-19,"For young people finding their way in the world, what it means to be normal and live an ordinary life are crucial concepts. But the Covid-19 pandemic has meant navigating a 'new normal' in which the very notion of ordinariness is destabilised. 'Reading for Normal' will work with young people to interrogate the 'connective tissue' of commonplace reality that currently feels out of reach. Recognising the value of literature for making sense of diverse experience, it will build a digital reading community to explore ideas of normality in recent young adult novels. The project will create an important record of young readers' responses to Covid-19 through their engagement with textual portrayals of everyday British life, and develop a framework for how they might support each other at a distance through shared reading practices. Outputs will be a journal article and monograph chapter, and a framework and guidance paper for teachers.",2020,-99,"The University of Roehampton, English & Creative Writing",6708.41,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02402,COV19\200323,"The Organisational, Financial and Human Impact of the Covid-19 Pandemic on the Christian Faith-Based Organization Service Sector in Great Britain","Faith-Based initiatives historically provided foundational pillars for the development of the welfare and service sectors in Britain. Of the c.15,000 Faith-Based Organizations (FBOs) that today provide significant scaffolding for contemporary social welfare needs (National Council for Voluntary Services UK Civil Society Alamanac, 2019) a substantial number are Christian. Britain has one of the highest rates globally of COVID-19 infection and excess mortality, and because of the extra demands on Non-Governmental welfare support services to buttress this distressed landscape, it is critically important better to understand the organisational health and durability of FBOs. This exploratory pilot study focuses on geo-mapping Christian FBOs in distress due to COVID-19 and to identify any particularly affected sectors. By also identifying the causal, consequential, contextual and strategic issues experienced, it will enable an assessment of initial and projected short to medium-term human, financial and organisational impacts on these FBOs and their services.",2020,-99,"Coventry University; Centre for Trust, Peace and Social Relations",12607.53,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C02403,COV19\201709,Supporting healthcare professionals during Covid-19: Non-verbal communication and arts-based approaches,"With the outbreak of Covid-19 healthcare professionals face new challenges to their non-verbal communication, as they adapt to the introduction of widespread use of Personal Protective Equipment, video-call consultations, social distancing and limiting of physical touch. The urgent need for research into this area is clear, demonstrated by proactive requests for help from London hospitals such as UCLH answered by Performing Medicine in the first weeks of the crisis. Through interviews with healthcare professionals and workshops with artists, this project will investigate how arts-based approaches can help to better understand the challenges faced by healthcare professionals during this period and to create, disseminate, and test resources to support them. A collaboration between Performing Medicine, sector leaders in non-verbal approaches to healthcare education, and the Emergency Medicine department at Guy's and St Thomas' Hospital, this research will use a live case study to gather insights into best practice in this area.",2020,-99,N/A,12937.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Unspecified,,,,Ireland,,"Policies for public health, disease control & community resilience | Health Systems Research",Communication | Health service delivery, +C02404,COV19\201019,The Languages of Covid-19: Implications for Global Healthcare,"Recent scholarship has identified that an interdisciplinary approach is urgently required to make sense of the biomedical, social and political implications of Covid-19. This project makes the case for the vital though to date underappreciated role that modern languages and translation studies, working together, can play in generating new understandings of the disease. Moving beyond the codes, contexts and cultural values that underpin anglophone articulations of Covid-19, the project aims to analyse what new facets or understandings of Covid-19 might be revealed by a linguistic and cultural encounter with non-anglophone languages and societies. The project will focus on the language used to frame Covid-19 in multilingual healthcare settings, in international public health campaigns and by patients across the globe, asking how these reveal new, and potentially useful, ways of thinking about and communicating the disease. The project will therefore be of benefit to medical practitioners, global policy makers and patients.",2020,-99,"Queen's University Belfast, School of Arts, English and Languages",13100,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C02405,COV19\200243,COVID and change in the public sector: A case study of newly qualified teachers,"The COVID pandemic is having fundamental impacts on society which will have repercussions for years to come. The positive response of the public sector to the pandemic is crucial if the long term health of society is to be maintained. This project considers the experiences of newly qualified teachers (NQTs), taking up their first career role having missed a considerable part of their work-based practice prior to employment. This makes them especially vulnerable in a period when schools will have little capacity for early career professional development, with a backdrop of a retention crisis, with many teachers already leaving the profession in their early years. This project will follow NQTs through their first year of teaching to understand the challenges and opportunities they face and how they can be better supported professionally and emotionally to inform practices and policies to ensure sustainability within the sector during and after the pandemic.",2020,-99,"Bishop Grosseteste University, Research and Knowledge Exchange Centre",12641.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions | Other secondary impacts, +C02406,COV19\201050,Voiceless? Classical Singers and COVID-19,"Classical singers are part of a fragile ecosystem of live music performance that is currently in deep-freeze during the current Covid-19 crisis, and that will likely suffer long-term damage as social-distancing measures and audiences' fear of crowds inhibit attendance at live performances for years to come. This two-year study will examine both short-term and long-term effects of Covid-19 on the creative and socio-cultural well-being of this discrete cohort of performers. Core data and analysis will be generated from individual interviews and focus group sessions with twenty professional singers of classical music from five countries in Europe and America, followed by a response-driven questionnaire of a wider sample of singers from the same countries. An important objective of the study is informing policymakers at both national and international levels, in order to ensure the well-being of this endangered classical music ecosystem and to give a voice to the artists sustaining it.",2020,-99,"Newcastle University, Music",12270.77,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C02407,COV19\200111,For better or worse? An immersive diary study of the effects of return to work policies on disabled employees,"One in five employees in the UK (19% of the working age population, or 7.9 million people 16-64) reported a disability in 2019. Although 53.2% or 4.2 million of disabled people were employed, an increase of 2% or 354,000 from the prior year, the unemployment rate is 2.5 times that of non-disabled people, as employers have historically resisted the range of accommodations instantly implemented across a wide range of occupations and workplaces during the home quarantine stage of the COVID19 pandemic. Most of these social distancing policies will be progressively released through the staged return to work with interruptions and updates projected until late 2021. Disability organizations warn against ""a return to ableism"" instead, as work accommodations originally exclusively extended to disabled people became a burden to undo for those without disability. This 18-months diary study follows 20 UK-based disabled employees/free-lancers who repeatedly renegotiate vulnerabilities and accommodations.",2020,-99,"Royal Holloway University of London, Strategy, International Business and Entrepreneurship",13084.28,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions", +C02932,unknown,"Social distancing, fears and resources over the course of Covid-19 pandemic: a vision longitudinal in population older adult of the City of Buenos Aires",,2020,-99,Universidad Nacional de Luján,4774.22,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C02933,unknown,Biotechnological production of the SARSCoV-2 complete protein S and synthetic peptides for diagnostic and therapeutic purposes,,2020,-99,"Universidad de Buenos Aires / Administración Nacional de Laboratorios e Institutos de Salud ""Dr. Carlos G. Malbran"" / Agidea SRL",55036.8,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pre-clinical studies", +C02934,unknown,RAPID DIAGNOSIS AND GENOTYPING OF SARS-COV-2 THROUGH THE USE OF NANOPORE TECHNOLOGY,,2020,-99,Universidad Nacional de Córdoba,84000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02935,unknown,"Development of immunoassays for optical detection, ultrasensitive and specific to SARSCoV-2 (COVID-19) viral antigens in samples biological using silver nanoparticles.",,2020,-99,Universidad Nacional de Córdoba,25158.01,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02936,unknown,Development of tools that contribute to the prevention of SARS-CoV2 infection.,,2020,-99,Universidad Nacional de San Martín,84000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,, +C02937,unknown,"""Prevalencia y patogenia en la infección por SARS-CoV-2 en la población pediátrica de AMBA (Área Metropolitana de Buenos Aires) Google Translate: Prevalence and pathogenesis in SARS-CoV-2 infection in the pediatric population of AMBA (Metropolitan Area of Buenos Aires)]",,2020,-99,Universidad de Buenos Aires,84000,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C02938,unknown,Development of serological kit (ELISA) for the detection of antibodies against SARSCoV-19,,2020,-99,Universidad Nacional de José Clemente Paz,41409.44,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02939,unknown,Parameter Meter Respiratory for Monitoring Mechanical Ventilation,,2020,-99,Universidad Nacional de San Martín,34459.74,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02940,unknown,"Development and production of critical reagents for diagnosis and treatment of COVID-19: Nanoantibodies, polyclonal IgY antibodies and recombinant proteins",,2020,-99,Instituto Nacional de Tecnología Agropecuaria,83989.32,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies, +C02941,unknown,Development and standardization of a neutralization technique for detection and antibody quantification specific neutralizers against SARS-CoV-2,,2020,-99,Universidad Nacional de Córdoba,64234.13,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02942,unknown,Cohort study on Incidence of COVID 19 symptomatic and its factors of risk of morbidity and mortality in patients with infection by HIV.,,2020,-99,Fundación IBIS para la Investigación de HIV/SIDA,6826.4,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity, +C02943,unknown,SARS-CoV-2 testing incidence of COVID -19 in health workers asymptomatic from two Hospitals of the AMBA.,,2020,-99,Fundación IBIS para la Investigación de HIV/SIDA,62153,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease surveillance & mapping, +C02944,unknown,Development and implementation of innovative methodologies for the diagnosis and follow-up of infection by the new SARS-CoV-2 coronavirus,,2020,-99,Universidad Nacional de Córdoba,84000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02945,unknown,EVALUATION OF THE EFFECT DRUG ANTIVIRAL IVERMECTIN AGAINST SARS-CoV-2,,2020,-99,"Universidad Nacional de Salta / Hospital de Pediatria ""Prof Dr. J P Garrahan"" / CONICET-Centro de Investigacion Veterinaria de Tandil / Universidad Nacional de Quilmes",84000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Therapeutics research, development and implementation",Pre-clinical studies, +C02946,unknown,"Molecular diagnosis of SARSCoV2 by RT-qPCR: optimization, scaling and risk stratification",,2020,-99,Universidad de Buenos Aires,26452.51,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02947,unknown,"Antihypertensive drugs that have targets the reninangiotensin system, does pulmonary ACE2 levels, thus favoring a greater entry of SARS COV-2?",,2020,-99,Universidad de Buenos Aires,6125.21,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C02948,unknown,Development of pseudovirus SARS-CoV2 to detect neutralizing antibodies COVID-19 in samples serological,,2020,-99,Consejo Nacional de Investigaciones Científicas y Técnicas,29952.72,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02949,unknown,Vitamin controlled trial High-dose D versus placebo to prevent complications evolutionary of patients infected by COVID-19,,2020,-99,Consejo Nacional de Investigaciones Científicas y Técnicas,83020,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,Clinical trials for disease management, +C02950,unknown,COVID -19: Viral kinetics and immune response to SARS-CoV-2,,2020,-99,Centro de Educación Médica e Investigaciones Clínicas,57153.6,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity", +C02951,unknown,IDENTIFICATION OF DETERMINANTS IMMUNOLOGICAL PREDICTORS AND MARKERS EVOLUTION OF THE PATHOLOGY IN PATIENTS INFECTED WITH SARSCoV-2,,2020,-99,Universidad Nacional de Córdoba,84000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C02952,unknown,Epidemiological surveillance of SARS-CoV-2 in waters residual and superficial. Quantitative evaluation of microbiological risk. Proposals for mitigation and pollution control (IP 233 and 785),,2020,-99,Consejo Nacional de Investigaciones Científicas y Técnicas / Universidad de Buenos Aires,106400,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Infection prevention and control,"Disease surveillance & mapping | Barriers, PPE, environmental, animal and vector control measures", +C02953,unknown,Development of protocols and kits nationals for extraction of Viral RNA and diagnosis of COVID-19 by PCR in time real,,2020,-99,Universidad de Buenos Aires / Universidad Nacional de San Martin,125842.5,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02954,unknown,"Detection and characterization molecular structure of SARS-CoV-2 in animals and surveillance epidemiological of possible reservoirs, amplifiers and / or virus transmitters",,2020,-99,Universidad Nacional de La Plata / Universidad Nacional de Santiago del Estero,49350,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission", +C02955,unknown,Design and manufacture of cabinets for making patient samples outpatients infected with COVID 19,,2020,-99,Comisión Nacional de Energía Atómica,12522.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02956,unknown,"Fast, simple production efficient and biosecure of recombinant proteins SARS-CoV-2 for purposes biotherapeutics and diagnostics for COVID-19",,2020,-99,Universidad Nacional del Litoral,84000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies, +C02957,unknown,One health: identification of the presence of Covid-19 in domestic and wild animals in two hotspots in Argentina,,2020,-99,One health: identification of the presence of Covid-19 in domestic and wild animals in two hotspots in Argentina,83733.16,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C02958,unknown,"Biosecurity capsule for COVID-19 patient transport, ARK",,2020,-99,Hospital Dr. Guillermo Rawson,18200,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,IPC in health care settings, +C02959,unknown,"Genomics of the SARSCoV-2 viruses that produce COVID19 in Argentina. Analysis comprehensive of genetic aspects, clinical and evolutionary strains indigenous peoples and their impact on diagnosis and epidemiology local and global",,2020,-99,Consejo Nacional de Investigaciones Científicas y Técnicas,83994.08,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations", +C02960,unknown,CREATION AND CHARACTERIZATION OF A COLLECTION OF BIOLOGICAL SAMPLES OBTAINED FROM POSITIVE INDIVIDUALS FOR INFECTION BY SARS-COV-2 WITHIN BIOBANK OF DISEASES INFECTIOUS (BBEICOVID19),,2020,-99,Universidad de Buenos Aires,84000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis, +C02961,unknown,Development of face masks use protection universal with properties microbicides for COVID19 virus deactivation,,2020,-99,Universidad Nacional de Córdoba,64470.67,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02962,unknown,"Proportional Microvalve ""Pneumatic micro valve national for respirators intensive care",,2020,-99,VENG SA,29400,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02963,unknown,Design and Development of a device with UV C radiation to decrease viral load of Covid 19 (SARS-CoV- 2) in surfaces,,2020,-99,Centro de Excelencia en Productos y Procesos Córdoba - Cámara de Industriales Metalúrgicos y de Componentes de Córdoba,40152,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02964,unknown,Development of methodologies fast molecular diagnosis and monitoring of SARS-CoV-2 infection,,2020,-99,"Hospital de Pediatría ""Prof. Dr. J P Garrahan""",49392,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02965,unknown,Development of diagnostic kits for molecular detection of the main viral agents disease causing severe acute respiratory,,2020,-99,DETx MOL SA,84000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics, +C02966,unknown,"Development of gels, films and polymeric coatings for the elaboration of materials of protection and inactivation of COVID-19 of different surfaces",,2020,-99,Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional del Sur - Universidad Nacional de Mar del Plata,17220,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02967,unknown,Omics strategies applied to eco-epidemiology of SARSCoV-2 in Argentina,,2020,-99,"Administración Nacional de Laboratorios e Institutos de Salud ""Dr. Carlos Malbran""",83991.39,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics", +C02968,unknown,Solutions and developments sustainable for certification of textiles and PPE (equipment for personal protection) for decrease the spread of COVID-19,,2020,-99,Instituto Nacional de Tecnología Industrial,83974.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02969,unknown,Development of a genomic test rapid detection for new Corona virus (SARS-CoV-2) causing COVID-19,,2020,-99,Universidad Católica de Cuyo,84000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02970,unknown,Respirator Development Emergency Mechanic,,2020,-99,Universidad Nacional de La Plata,16095.02,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings", +C02971,unknown,Elimination of SARS-CoV 2 from papers and water through ultraviolet radiation,,2020,-99,Instituto de Farmacia y Bioquimica. IBYF Centro de investigación e innovación tecnológicaCENIIT Universidad Nacional de La Rioja-UNLAR,57074.91,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C02972,unknown,Ventilator respirator for intensive care,,2020,-99,IDIT - CONICET,19705.64,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02973,unknown,"Design, construction, evaluation and certification of a mechanical fan for assisted / controlled breathing aimed at improving capacity national response to COVID-19 pandemic.",,2020,-99,Comisión Nacional de Energía Atómica,81585,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02974,unknown,Cycler Development Automatic Resuscitator for Assist Patients with Respiratory insufficiency,,2020,-99,Universidad Nacional de Rafaela,82099.43,Other,Not applicable,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Innovation,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02975,unknown,Clinical development of a serum equine hyperimmune therapeutic against COVID-19,,2020,-99,Inmunova S.A. - INSTITUTO BIOLÇÿGICO ARGENTINO S.A.I.C.,168000,Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Therapeutics research, development and implementation",Pre-clinical studies, +C02976,unknown,Development of a method responsive and inexpensive for detect antibodies against SARS-Cov-2,,2020,-99,Zelltek SA,62027.42,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C02977,unknown,Simplified Monitoring of Patients in Situation Mass Hospitalization,,2020,-99,Universidad Nacional del Sur,46349.1,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C02978,unknown,Chronobiological challenges associated with social isolation,,2020,-99,Universidad Nacional de Quilmes,11200,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C02979,unknown,"Prediction of the impact of climate, confinements social and the different public health strategies about the Covid-19 pandemic through modeling spacetime based on agents",,2020,-99,Universidad Nacional de Entre Ríos,83588.97,Other,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities, +C02980,unknown,Projection of trends and evaluation of scenarios intervention for the epidemic COVID-19 in Argentina through Modeling and Computational simulation,,2020,-99,ICC-CONICET,44100,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities, +C02981,unknown,Big data and experiments massive for the synthesis of real-time information on the impact of COVID-19 and the measurements for your containment in the population,,2020,-99,Instituto de Física de Buenos Aires (IFIBA - CONICET),19958.4,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities, +C02982,unknown,Implementation of a system based on health information in free software for management place of epidemics in municipalities,,2020,-99,Universidad Nacional de Entre Ríos,37536.52,Unspecified,Not applicable,Not Applicable,Not applicable,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Health Systems Research,Health information systems, +C02983,unknown,"Prevention, control and monitoring multidimensional and multiscalar health effects and socio-territorial areas of the pandemic by COVID19 and the measures of ASPO in Argentina",,2020,-99,"Universidad Nacional de San Martin; IIFP - CCT CONICET La Plata, Universidad Nacional de General Sarmiento; CENTRO CIENTIFICO TECNOLOGICO CCT CONICET TUCUMAN",234259.76,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities, +C02984,unknown,Analysis and traceability of spread of the COVID19 virus through devices mobiles,,2020,-99,Universidad Nacional de Cordoba; Universidad Nacional del Centro de la Pcia de Buenos Aires,118020,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Digital Health,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C02985,unknown,Resource Optimization hospitals from a management centralized,,2020,-99,Universidad Nacional del Centro de la Provincia de Buenos Aires,74088,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Digital Health,,,Argentina,Argentina,,, +C02986,172650,Prevention of COVID-19 with high dose Oral Vitamin D supplemental Therapy in Essential healthCare Teams (PROTECT),"During the COVID-19 pandemic, despite personnel protection equipment, healthcare workers are 10 times more likely to contract the infection due to their exposure to patients and co-workers with unknown or confirmed COVID19 infection. Any one withdrawn due to infection has an amplified negative impact on care delivery, further increasing the burden on those remaining and on our healthcare system. Studies have shown that Vitamin D supplementation decreases the risk of common respiratory illnesses by about 20%, particularly in those with lower vitamin D levels. Lower Vitamin D levels is a common occurrence among Canadians, particularly in the fall and winter, that is, at the expected of the second wave of infection. Whether high-dose vitamin supplementation can help decrease the risk of COVID 19 infection in health care workers is yet to determined. In this 16-week randomized clinical trial to be started in September 2020, 2414 healthcare workers in the greater Montreal area will be allocated by chance to receive: (i) a high bolus dose of vitamin D followed by weekly doses of vitamin D or (ii) placebo bolus and placebo weekly dose, for 16 weeks. Every two weeks, participants will perform a nasal swab to be send to analysis. This study will examine whether healthcare workers receiving vitamin D have a lower risk of COVID-19 infection, milder infection, and/ or a shorter infection duration, compared to the control group. If vitamin D proves effective to decrease COVID 19 infections, severity, and duration, it may be the cheapest, most easily applicable approach (in addition to social distancing and personal prevention equipment) to prevent COVID-19 infection in at-risk healthcare workers. If the benefit also translates in fewer and shorter withdrawals from the workforce, it may consubstantially reduce the burden on healthcare system and ensuring sufficient healthcare workforce to better tackle the current pandemic.",2020,2020,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec) Pediatrics",3168747,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C02987,172710,Rapid Prototyping and Deployment of a Therapeutic Pan-Coronavirus Fusogenix DNA Vaccine Engineered to Eliminate ADE,"In this project, this team will rapidly develop, validate and clinically evaluate a novel DNA Vaccine against COVID-19 utilizing well-validated Fusogenix proteolipid vehicle (PLV) intracellular delivery platform. The use of a plasmid DNA vaccine will allow us to utilize multiple epitopes from key immunogenic SARS-COV-2 proteins, generating protection against structural components of the novel coronavirus, which should not only protect against viral entry but provide a robust cell-based response during active infection. Working with an international multi-disciplinary team including investigators at University of Alberta, Dalhousie University, Entos Pharmaceuticals, VIDO, EpiVax, Virscio and a pharmaceutical partner, we will rapidly prototype, validate and clinically evaluate a pan-coronavirus DNA vaccine. Clinical trials will be initiated at the Canadian center for Vaccinology in Halifax within 8 weeks of project initiation, with the goal of a commercial release within one year.",2020,2020,University of Alberta Experimental Oncology,3131250,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Nova Scotia,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C02988,172635,"ANTI-THROMBOTIC THERAPY TO AMELIORATE COMPLICATIONS OF COVID-19 (ATTACC): A randomized, international, multi-centre, adaptive, controlled clinical trial","COVID-19 is associated with an unusually high risk of blood clots. Small studies have suggested that anticoagulant (blood thinning) medications that prevent blood clots from forming or travelling may improve the health and survival of hospitalized patients with COVID-19. The goal of this study is to establish whether anticoagulants called heparins can improve outcomes in patients with COVID-19. This study will compare patients who are treated with higher doses of heparin to those that receive usual clinical care, which typically includes low dose heparin. It will measure whether a patient requires intubation (a breathing tube) and need to be on a ventilator, or dies within 30 days of the treatment. It will also monitor patients for other important outcomes such as bleeding, heart attacks, and blood clots. This trial follows a Bayesian adaptive design. Adaptive designs can make clinical trials more flexible by taking into account early results to modify the course of the trial. This is particularly helpful during the COVID-19 pandemic because the trial will make better use of resources in a short timeframe. The trial also uses a randomization method called response-adaptive randomization which allows more patients to be assigned to the superior treatment as the trial progresses. The trial will enroll up to 3000 patients in Canada, the US, Brazil, and Mexico. Participants will be randomly assigned to the investigational arm will receive higher dose unfractionated heparin or low-molecular-weight heparin for up to 14 days. Participants assigned to the control arm will receive usual clinical care, which may include low dose unfractionated heparin or low-molecular-weight heparin. This trial includes collaborations with two large Canadian research networks, the Canadian Venous Thromboembolism Research Network (CanVECTOR) and the Canadian Critical Care Trials Group (CCCTG), and is being conducted in partnership with another global COVID-19 trial called REMAP-CAP.",2020,2020,University of Manitoba Internal Medicine,2680002,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III | Randomized Controlled Trial",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Phase 3 clinical trial | Therapeutic trial design",2020 +C02989,171496,Canadian Treatments for COVID-19: SOLIDARITY [Added supplement: COVID-19 Variant Supplement],"This proposal is for an adaptive, randomized, open-label, controlled clinical trial for the treatment of COVID19, in collaboration with countries around the world, working in solidarity with the World Health Organization. We are currently active in 22 centres across the country, have randomized 70 patients at time of writing across multiple provinces, and are funded for 440 participants through the first rapid response fund from CIHR for coronavirus. This proposal is to expand to 80 sites across the country and enrol thousands of patients, over the course of this and subsequent waves of the COVID19 pandemic over the next 1-2 years. Eligible and consenting hospitalized patients with COVID19 are being randomized to receive either standard-of-care or the study medication plus standard of care. Current approved study arms include: 1. Lopinavir/ritonavir 400mg/100mg PO BID for 14 day plus optimized supportive care, OR 2. Hydroxychloroquine 800mg BID for 1 day then 400mg BID for 10 days plus optimized supportive care, OR 3. Remdesivir 200mg IV on day 1, followed by 100 mg IV daily infusion for 9 days plus optimized supportive care, OR 4. Optimized support care. Inclusion criteria will be: Age = 18 years of age, has laboratory-confirmed SARS-CoV-2 infection, and is admitted to hospital at a participating centre. The primary outcome will be mortality at hospital discharge. CATCO is incorporated into the WHO Solidarity Global Trial, with interim results from many countries being reviewed by an independent Global Data Monitoring and Safety Committee. This Committee will decide how often to conduct interim analyses and when to declare effectiveness, futility, or harm. It is anticipated that many thousand patients will be recruited into this trial, with over 2000 globally at time of writing. The larger the numbers entered, the more accurate the results will be, both for all patients and for targeted subgroups; the numbers that can be entered will depend critically on how large the pandemic becomes. Inclusion criteria will be: Age = 18 years of age, has laboratory-confirmed SARS-CoV-2 infection, and is admitted to hospital at a participating centre. The primary outcome will be mortality at hospital discharge. CATCO is incorporated into the WHO Solidarity Global Trial, with interim results from many countries being reviewed by an independent Global Data Monitoring and Safety Committee. This Committee will decide how often to conduct interim analyses and when to declare effectiveness, futility, or harm. It is anticipated that many thousand patients will be recruited into this trial, with over 2000 globally at time of writing. The larger the numbers entered, the more accurate the results will be, both for all patients and for targeted subgroups; the numbers that can be entered will depend critically on how large the pandemic becomes.",2020,2022,University of British Columbia,2560000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C02990,172638,A Randomized Open-Label Trial of CONvalescent Plasma for Hospitalized Adults With Acute COVID-19 Respiratory Illness (CONCOR-1),"The COVID-19 pandemic has affected over 4 million people and caused over 300,000 deaths worldwide. There is no known treatment for COVID-19 and it can take many months before a vaccine becomes available. There is a fairly significant body of anecdotal evidence that suggests the plasma from recovered COVID-19 patients - called convalescent plasma - may be an effective method of treating the virus. Convalescent plasma contains proteins called antibodies that can fight off the virus. Taking convalescent plasma from a person who has recovered from COVID-19, and infusing it into someone else who is sick in the hospital with COVID-19 infection might help them get better. The CONCOR-1 trial will tell us if convalescent plasma can help patients with COVID-19 avoid needing a respirator or dying. For the trial, COVID-19 patients who are admitted to the hospital will receive either convalescent plasma or the current standard of care by random selection, like flipping a coin. Patients will be watched for 30 days to see if convalescent works and whether it causes side effects. The CONCOR-1 trial will include 1200 patients from 60 hospitals across Canada and in 3 hospitals in New York City. It is important that we study convalescent plasma properly so that we can know if it is something that blood banks and blood suppliers should be providing to other patients with COVID-19. With our large team of experts from across Canada and a network of hospitals already in place, we plan to complete this large clinical trial quickly in the span of 9 months.",2020,2020,McMaster University Medicine,2229204.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2020 +C02991,172627,Anti-Coronavirus Therapy (ACT) to prevent COVID-19 disease progression: a clinical trial platform,"COVID-19 has been diagnosed in millions of persons and has caused several hundred thousand deaths. Effective treatments are urgently required. We have created the ""Anti-Coronavirus Therapies (ACT) to prevent COVID-19 disease progression"" trials platform to rapidly evaluate whether several commonly available interventions can be repurposed for the treatment of COVID-19 disease. The specific aims of our research are to determine whether treatments that: (a) reduce the levels of virus in the body, (b) reduce the response by the body to the infection (i.e., inflammation), and (c) prevent blood clotting can prevent COVID-19 disease progression. We will test these treatments alone and in combination in two trials: (1) Outpatient trial: here we are trying to patients diagnosed with COVID-19 from needing to go to hospital. (2) Inpatient trial: here we are trying to prevent patients with COVID-19 who are already hospitalized from being admitted to the intensive care unit and from dying. The trial started in Canada on April 21 and will eventually include about 4,000 patients from at least 100 centres and at least 12 countries around the world.",2020,2020,McMaster University Medicine,2202839.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C02992,172631,Anticoagulation and Convalescent Plasma ICU Trials in REMAP-CAP,"Current recommendations for managing critically ill patients struggling with COVID-19 focus on supportive care and prevention of complications. As the development of vaccines and new drugs against SARS-CoV-2 virus will take several months to years, there is an urgent need to optimize the management of hospitalized COVID-19 patients. Recently, two existing interventions have been proposed to treat patients afflicted with COVID-19: 1) therapeutic anticoagulation with heparin to counteract the increased risk of blood clots in these patients, and 2) convalescent plasma from patients cured from COVID-19 to provide direct antibodies against SARS-CoV-2. Our two trials will assess the efficacy of these two different therapies to prevent clinical deterioration and improve survival, and will use existing research infrastructure, the international REMAP-CAP platform, to leverage Canada's investment and put our country at the forefront of our fight against COVID-19. Our research team is already recruiting patients with COVID-19 in 150 centres from 15 countries and we are planning to expand recruitment in low- and middle-income countries in Asia, Africa and South America. Our study a unique opportunity to scale-up an existing international research effort, enhance the scope of a large adaptive clinical trial platform, make major economies of scale, rigorously and quickly evaluate promising but unproven relatively inexpensive and readily available interventions that may improve the health of hundreds of thousands of patients around the world.",2020,2020,Université Laval Anesthesiology & Critical Care Medicine,1632424.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2020 +C02993,172729,Canadian COVID-19 Prospective Cohort Study (CanCOV),"The Canadian COVID-19 Prospective Cohort Study (CANCOV) is the first Canadian study to provide a comprehensive evaluation of early to 1-year outcomes in 2000 patients with COVID-19 infection and their family caregivers. This study will be conducted in Quebec, Ontario, Alberta and British Columbia, the hardest hit provinces in Canada. CANCOV is built on the GEMINI (GEneral Internal Medicine INpatient Initiative) and RECOVER (REhabilitation and reCOVERy after critical illness) established research platforms. Through the CANCOV program of research, we will: 1) characterize the myriad health consequences of COVID-19 including their short and long-term outcomes (recruited from the community and hospitals) and those of their family caregivers, 2) determine the clinical risk factors, timing and pace of recovery across the spectrum of COVID-19 disease, 3) provide detailed clinical descriptions for genetic, basic science, translational and multi-omics research inquiry, and 4) facilitate the creation of prediction models and tools using machine learning and artificial intelligence, as well as secondary clinical studies. Our senior and diverse team of investigators, many with extensive research experience during SARS, will shorten the time to translate knowledge into practice through multiple rapid knowledge to action cycles throughout this project. Insights from this large-scale project will enable Canada to improve COVID-19 clinical care and decision-making regarding service provision, and response to this global pandemic.",2020,2020,University Health Network,1584375,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C02994,172758,Canadian COVID-19 Emergency Department Rapid Response Network,"Coronavirus Disease 2019 (COVID-19) has resulted in more than 4 million infections and 275,000 deaths globally. Yet, pressing questions about its prevention, diagnosis, treatment, and resource allocation remain unanswered. This hinders evidence-based clinical decision-making, particularly in Emergency Departments. The Emergency Department is a place where the sickest patients present for early evaluation and care. Emergency providers are making decisions on whether and when to discharge patients or put patients on life-sustaining measures, such as artificial ventilation. However, these decisions are currently based on subjective judgement. We have created a national network of collaboration to address these knowledge gaps. Our network includes 51 collaborating Emergency Departments in 8 provinces. We will collect prospective and retrospective data on short-term outcomes from Emergency Department patients with suspected and confirmed COVID-19, follow patients by telephone after discharge to see if they developed complications and ask them about their quality-of-life after COVID-19. We will use these data to develop and test clinical decision rules, which are simple user-friendly algorithms or point-scoring systems that predict an outcome, for example which patients have COVID-19 in advance of diagnostic testing, or safe Emergency Department discharge. We are a team of health researchers, clinicians, patients and knowledge users with expertise in international networks, clinical decision rules, diagnostic testing, registries, and knowledge translation. Our work will enhance local and national collaborations to mitigate COVID-19 and its consequences by improving Emergency Department treatment and decision-making. We will also link with other ongoing studies to enable our group and others to take advantage of the rich dataset we are creating to answer more questions to help answer local, national and international questions about COVID-19.",2020,2020,University of British Columbia Emergency Medicine,1584375,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C02995,"172722, 175515, 175569","Analysis of Antibody Neutralization Efficiency and Cellular Immunity in SARS-CoV-2-Positive Individuals Identified in At-Risk Individuals [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","As the COVID-19 pandemic continues its deadly course around the globe, research efforts are closely focused on viral immunity, antibody responses, and vaccine development. Increasing data from multiple reputable international medical sources now indicate that exposure to the COVID-19 virus induces an antibody response in nearly all exposed individuals. However, questions remain about the protective value of these antibodies against repeat exposure to the virus and how long this protection will last. Furthermore, it is unclear whether there are differences in the virus-neutralizing ability of antibodies produced by asymptomatic carriers of the virus and individuals that develop severe COVID-19 infection. Answers to these important questions will enable us to predict the likelihood of additional waves of COVID-19 as well as inform public health efforts and vaccine development. For our study we will recruit a total of 1,000 healthy primary school teachers, daycare personnel, frontline medical workers in hospitals, and elderly people living in retirement homes. We will monitor them every two weeks for the virus and monthly for antibodies. We will regularly report back the data to the participants. The information learned from our laboratory will have five major outcomes: 1) It will enable early detection of infection and thereby greatly reduced the spread of the virus; 2) We will acquire a better sense of the numbers of asymptomatic and symptomatic individuals exposed to COVID-19; 3) Antibodies in the blood of those infected will be tested to see how well it can neutralize the virus; 4) Critical information about immunity to COVID-19 and how long the immunity will last will be shared with the scientific community and local/regional/national health authorities; and 5) This new knowledge will help vaccine developers make the right decisions about how to create their vaccines and how to give them to all of us.",2020,2022,"University of Ottawa Biochemistry, Microbiology & Immunology",2050500,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +C02996,172712,REinfection in COVid-19 Estimation of Risk (RECOVER),"Studies done with human coronaviruses (hCoV) have shown that antibodies rise on average 12 days after the onset of symptoms, are higher with more severe disease and seem to decrease the risk of reinfection for 1-3 years. Participants challenged with the same virus (hCoV 229E) 8-12 months after being infected with hCoV still developed symptoms and shed virus. Thus, if reinfection, whether symptomatic or not, occurs with viral shedding, achieving natural herd immunity against COVID-19 is unlikely. Awaiting a vaccine that would protect the entire population, there is hope that short-term natural immunity following natural disease can be achieved. However, we do not know at this point in time if COVID-19 positive patients in whom we detect an immune response have a long-lasting response and if this response protects them against reinfection and viral shedding There is a need to know these answers to plan for future actions. If an antibody response is not long-lasting and protective against viral shedding, then herd immunity is not a goal to aim for, as vulnerable patients will remain at risk; individuals having recovered from the disease may get re-infected and be a source of infections for others. In such a case, other non-pharmacological interventions will be necessary until an efficacious vaccine or therapeutic agent becomes available. We aim to estimate the risk of reinfection with SARS-CoV-2 in healthcare workers (HCW) who have already been infected with COVID-19 and aim to study antibody response and levels in asymptomatic and symptomatic HCWs with confirmed COVID-19 reinfection over a 1-year period. Findings from this study will allow public health decision-makers to decide on future strategies for deconfinement/reconfinement and pandemic management. The 6-month results will be shared with public health. Showing that COVID-19 does not protect against mild reinfection or viral shedding will completely change the paradigm under which we are operating currently.",2020,2020,Centre hospitalier universitaire Sainte-Justine,1584353.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +C02997,"172639, 175550, 175565","Computer-aided discovery of synergistic drug combinations with Remdevisir for COVID-19 through mechanism-based drug repurposing and combinatorial organoid screening. [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","With more than 4 million cases and over 300,000 deaths worldwide, it is critical to find an effective treatment against COVID-19 and to find it fast. Hopes for ending the pandemic largely rely on new vaccines, however the development of vaccines typically takes years and even if one is available today (which is not), its approval will take more than a year in the most optimistic scenario. Thus, the only realistic option for rapid COVID-19 treatment is drug repurposing. Drug reprofiling (repurposing) implies the use of existing drugs approved for other indications, and yet showing useful activity against SAR-CoV-2 virus. One well-known example of this strategy is remdesivir, currently the most promising treatment against COVID-19, and which was originally developed as Hepatitis C drug. Although very promising, remdesivir is still modestly efficient against COVID-19 and hence, if one could further boost its effectiveness by using it in a synergetic combination with another reprofiled drug, the pandemic might finally see the resolution. This consortium of national and international scientists wants to identify such much-needed SARS-CoV-2 inhibitor among known drugs, which then will be used either as stand-alone therapy for COVID-19 or a synergetic 'booster' for remdesivir. This team of scientists was recently awarded four COVID-19 rapid response grants to build a state-of-the-art organoid-based screening platforms established at UBC CL3 infectious disease facility, working in sync with high-resolution crystallography and artificial intelligence-enhanced molecular modeling and imaging platforms. We are ready and prepared to push forward this project even in this extremely condensed 1-year timeframe. The proposed research will generate high quality data on COVID-19 treatments shared through extensive international collaborations, will initiate critical clinical trials, and will position Canada as a world leader in the global fight against the pandemic.",2020,2022,University of British Columbia Urologic Sciences,1662912.32,Human Populations | Other,Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C02998,172762,SUrveilling Prospective Population cOhorts for COVID19 pRevalence and ouTcomes in Canada (SUPPORT-Canada),"The ability to assess the spread and severity of the COVID-19 pandemic is central to our ability to inform a targeted and proportional public health response, both now and in the future. Here, we will leverage major prior investments into Canadian health platforms to enable the rapid development of a Canadian COVID-19 cohort and research resource that will enable the real-time assessment of population susceptibility and prevalence and act as a critical resource to support both population and clinical-level research at a national scale. The initiative titled SUrveilling Prospective Population cOhorts for COVID19 pRevalence and ouTcomes in Canada (SUPPORT-Canada) aims to capture data and biologics to enable population-level surveillance, and enable researchers and clinicians to find factors contributing to COVID-19 susceptibility and severity, thus identifying high risk individuals or communities across Canada. Building on partnerships between the Canadian Partnership for Tomorrow's Health, Canada's largest population cohort, the University Hospital Network, and regional partners, SUPPORT-Canada is a collaborative effort, with both national and global partners, that will and capture critical short- and long-term COVID-19 clinical features from affected and unaffected Canadians. Our platform has been designed to integrate with national and global research efforts to support clinical, immunological and genetic studies of COVID19. Our integrated approach will enable rapid data sharing and translation of findings to the public health and research community. The identification of diagnosed and symptomatic participants within the Canadian population will enable rapid surveillance that can support our public health agencies at the community and the individual level. Capturing COVID-19-specific information will enable us to provide the research community timely data to support surveillance, prevention and risk factor research.",2020,2020,Ontario Institute for Cancer Research,1579114.5,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C02999,"172753, 175526, 175572","Implementation of serological and molecular tools to inform COVID-19 patient management [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a novel virus that causes COronaVIrus Disease 2019 (COVID-19). There is considerable variability in symptom severity and outcomes among patients infected by SARS-CoV-2. Linking genome and viral sequencing information to antibody (immune) response and other biological information (sex, age, ancestry, symptom severity, comorbidities, and outcome) may identify characteristics of patients that are associated with poor and favourable outcomes. This study will address three aims. Aim 1: Identify the characteristics of the antibody response that result in maintained immune response and better patient outcomes. Aim 2: Determine impact of genetic differences on COVID-19 infection severity and immune response. Aim 3: Determine impact of different viral strains on antibody response and patient outcomes. Patients with COVID-19 will be recruited from Sinai Health System, University Health Network, Baycrest Health Sciences and William Osler Hospital System. Patients seen in the emergency department with mild symptoms as well as hospital in-patients with more severe symptoms will be consented. Blood samples will be collected when patients are in hospital and 6 months and 1 year after COVID-19 diagnosis. Neutralizing antibody levels will be measured at all time points. Patient and viral genomes will be sequenced. Statistical analysis will be used to test for associations between antibody levels, genetic variation, viral genome variation, and patients' characteristics including age, sex, ancestry, comorbidities, and symptom severity. This study will link serological, genomic and patient characteristics to provide a comprehensive understanding of factors that contribute to variability in clinical symptoms and outcomes among COVID-19 patients. Evidence from this study will determine if immune response, viral strain and genome sequencing are effective for the diagnosis, prognosis and management of patients with COVID-19.",2020,2022,Sinai Health System,1639957.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C03000,172744,Sedating With Volatile Anesthetic Agents in Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival (The SAVE-ICU trial),"Up to 40% of COVID-19 patients can incur severe lung failure needing life-saving supportive care using a ventilator (breathing machine) to treat dangerously low oxygen levels. Unfortunately, 40 to 80% of ventilated patients with COVID-19 will die despite best medical care. All patients needing a ventilator require intravenous sedative or sleep inducing medications to tolerate this uncomfortable procedure. High volume of COVID-19 patients needing life saving ventilation and high quantities of sedative medications consumed by these patients has led to a worldwide shortage in intravenous sedative drugs. An alternative method for delivering sedation that can ease pressure on intravenous sedation stocks and possibly accelerate patient recovery is by using inhaled volatile anesthetic agents. Inhaled volatiles are used safely every day in operating rooms, widely available and cheap when providing sedation to ventilated COVID-19 patients. Inhaled volatiles have also shown to reduce lung inflammation and improve oxygen levels that may reduce time spent on a ventilator and improve survival in COVID-19 patients with severe lung injury. Our objective is to evaluate differences in time spent on a ventilator, time spent in intensive care units and survival in adult patients with known or suspected COVID-19 who receive either inhaled or intravenous sedation. After hospital discharge, we will also interview survivors and assess for any differences in satisfaction and activities of daily living between patients who received the two types of sedation. This study is unique and first to addresses the drug shortage issue that all hospitals are facing, and provides a readily available and tested solution. It also provides a potentially effective treatment to improve outcomes for our sickest COVID-19 patients in the absence of an effective vaccine or other therapy.",2020,2020,"Sunnybrook Research Institute (Toronto, Ontario) Anesthesia",1515486,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2020 +C03001,"172743, 175511, 175576","The COVID-19 Hospital Analytics Laboratory: Improving the Clinical, Organizational, and System Response to COVID-19 [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","Hospital care has been dramatically reorganized to respond to the COVID-19 pandemic, with an urgent need to preserve scarce resources like ventilators and personal protective equipment. Yet, there is minimal evidence about how to care for patients with COVID-19 in hospital and how to maintain high quality non-COVID care during the pandemic. Detailed clinical data, such as patient vital signs or medications, are needed to study COVID-19 and its individual- and system-wide effects. These data are available in hospital computer systems but have not been widely collected and shared for research. The General Medicine Inpatient Initiative (GEMINI) has collected detailed clinical data from >340,000 admissions at 7 hospitals in Ontario, making it the largest inpatient repository about adult medicine in Canada and a valuable data source to study COVID-19. We propose to create the COVID-19 Hospital Analytics Laboratory by extending GEMINI to the 30 largest hospitals in Ontario, representing 70% of acute medical/ICU beds in the province. We will collect detailed clinical data from all medical and ICU admissions, including COVID-19 and other medical illnesses. Data will be linked to ICES longitudinal population datasets and updated every 1-3 months to create a globally unique platform that enables advanced analytics and machine learning and includes a diverse sample of patients, meaning research insights will be widely applicable. This platform will address all 5 CIHR objectives by supporting a breadth of research focused on improving hospital care in the setting of COVID-19. Data will be accessible to global experts in artificial intelligence, operations engineering, population modeling, public health and clinical epidemiology. Our first two research priorities will be to improve understanding and prediction of clinical outcomes in patients hospitalized with COVID-19 and to study how the organization of hospital care in the setting of COVID-19 affects patient outcomes.",2020,2020,Unity Health Toronto General Internal Medicine,1598228,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C03002,"172707, 175503",Development of Vaccines to Prevent SARS-CoV-2 Infection of High Risk Individuals [Added supplement: COVID-19 Variant Supplement],"The physical-distancing strategy currently implemented in the Covid-19 pandemic in Canada has been very effective in preventing the vast majority of Canadians from being infected by SARS-CoV-2. This essential short-term strategy is saving lives, but paradoxically will leave most of our citizens without protective immunity and a recurrent outbreak is both predictable and likely without an effective Canadian vaccine strategy. A global effort has been initiated to identify an effective Covid-19 vaccine, testing a variety of vaccine platforms and strategies. Unfortunately, few of these are being developed, tested or manufactured in Canada leaving our population in a very perilous situation where our vaccine needs could be de-prioritized by foreign governments. This project is aimed at bringing together a multi-disciplinary team of scientists and clinicians to rapidly create and manufacture a vaccine to prevent a second wave of infections. We are using scientists and infrastructure, already available in Ottawa, Montreal, Calgary and the US (Covington Louisiana) to rapidly create, compare and contrast different vaccine strategies in animal models. Our best candidate will then be manufactured in a pure enough form to inject in humans. We will complete all of the data and regulatory documents to prepare an application to Health Canada to allow the initiation of a clinical trial in healthy volunteers.",2020,2022,Ottawa Hospital Research Institute Cancer Therapeutics,1491612.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C03003,"172709, 175496",Rapid bench-to-human development of safe and effective aerosol vaccine strategies against Covid-19 [Added supplement: COVID-19 Variant Supplement],"The pandemic of Covid-19 caused by respiratory SARS-CoV-2 infection has brought the world to a standstill. The physical-distancing strategy currently implemented in the pandemic aims to prevent the majority of Canadians from being infected by SARS-CoV-2. While this is an essential short-term strategy to save lives, it will paradoxically leave the majority of our citizens without protective immunity against Covid-19. Thus, the majority of Canadians will be susceptible to the next waves of Covid-19. The only effective way to prevent new outbreaks from getting out of control is to establish herd immunity via implementing a safe and effective vaccination program prior to the next waves of Covid-19. High-risk Canadians including healthcare workers, seniors and indigenous people are especially in need of such vaccine-induced protective immunity. A global effort has been initiated to identify effective Covid-19 vaccines, testing a variety of vaccine platforms and strategies. Unfortunately, only a few of them are being developed and tested in Canada and almost none of them are designed to target respiratory mucosal immunity. To fill the gap, via the effort from a multi-disciplinary McMaster Team we have been rapidly developing innovative recombinant viral-vectored Covid-19 vaccine strategies to target the desired respiratory mucosal immunity. Our Team has internationally recognized reputation in bench-to-human translational vaccine research. Particularly relevant to the proposal is our strong expertise in advanced viral vector bioengineering, vaccine efficacy testing in small animal models at CL3 facility, clinical-grade vaccine production at GMP manufacturing facility, optimized inhaled aerosol vaccine delivery method, and clinical vaccine trials. We are confident that our project will make available to Canadians a superb, needle/pain-free vaccine strategy capable of potent respiratory mucosal protection against Covid-19.",2020,2022,McMaster University,1480238.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Characterisation of vaccine-induced immunity,2020 +C03004,"172654, 175540",Cellular Immuno-Therapy for COVID-19 Induced Acute Respiratory Distress Syndrome: the CIRCA-19 Trial [Added supplement: COVID-19 Variant Supplement],"The number of patients with the novel COVID-19 disease continues to rise world-wide. Approximately 20% of patients require hospitalization, and up to a quarter of these need intensive medical care, mainly due to intense inflammation (swelling) of the lung called 'acute respiratory distress syndrome' or ARDS. This interferes with the lung's ability to exchange oxygen, requiring a machine to support their breathing called a ventilator. Unfortunately, about half of patients who need a ventilator because of COVID-19 lung disease will not survive. We have no specific therapy to treat the lung swelling in these patients. Mesenchymal stromal cells, often termed 'MSCs', have anti-inflammatory effects that can reduce lung swelling in animal models of ARDS. As well, therapy with MSCs in humans has been shown to be safe, with some promising results in patients with severe inflammation due to uncontrolled infections as well as lung swelling due to ARDS. The few small clinical studies using MSCs to treat COVID-19 patients were not properly designed to assess the benefit of MSC therapy. The proposed Cellular Immuno-Therapy for COVID-19 related ARDS (CIRCA-19) trial is a randomized and placebo-controlled study designed to test whether giving MSCs to patients with severe lung swelling due to COVID-19 disease will decrease the need for a ventilator and whether this novel therapy will also have other important benefits such as improving survival and reducing the injury to vital organs like the heart, lungs and kidneys. The MSCs will be obtained from umbilical cords that are harvested during Caesarian section, and then grown in a specially equipped clinical-grade cell manufacturing facility at The Ottawa Hospital using Health Canada approved processes. We have rapidly deployed a multidisciplinary team and have already submitted the study to both Health Canada and Research Ethics for approvals, and we anticipate treating our first patient in early June 2020.",2020,2022,Ottawa Hospital Research Institute Regenerative Medicine,1408844.93,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2020 +C03005,172658,"Rapid research in the CHILD Cohort to inform Canada's response to the COVID-19 pandemic: investigating the prevalence and predictors of SARS-CoV-2 infection, and the health and psychosocial impact of the COVID-19 pandemic on Canadian families","The COVID-19 pandemic is affecting everyone. Millions of Canadians will be infected by the novel coronavirus, but only a few will develop severe COVID-19 disease. Others will have mild symptoms, or none at all. We don't know why some infected people get very sick and others do not, and we don't know the true rate of infection in the population. Social distancing policies and school and business closures have helped slow the spread of COVID-19, but we don't know how they will affect mental health and wellbeing (especially in children) in the long term. These are urgent questions that must be answered quickly to control outbreaks and minimize the unintended consequences of pandemic management policies. We will study the direct effects of coronavirus infection and the indirect effects of the COVID-19 pandemic in the existing CHILD Cohort Study. CHILD involves 3500 families in BC, Alberta, Manitoba and Ontario who have been followed since before their children were born in 2008-2010. Most recently, children provided detailed health data and blood samples in 2018-2020 (just before the pandemic), providing a unique opportunity to study how children's pre-pandemic health and immune status influences the risk and outcome of coronavirus infection. We will now ask all CHILD family members to report COVID-19 symptoms using a text messaging system, and provide a few drops of blood for COVID-19 antibody testing using a simple at-home collection kit. Families will also complete surveys about their physical and mental health, behaviours and emotions during the pandemic. This study will help us understand how Canadian families are being affected - both directly through infection and indirectly through pandemic management policies. Our research will provide important real-time data to Public Health authorities about coronavirus infection, symptoms, transmission and immunity in 12,000 Canadians in 4 provinces (CHILD children, siblings, parents) to inform Canada's COVID-19 response.",2020,2020,University of Manitoba Pediatrics and Child Health,1192346.25,Human Populations | Other,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Manitoba,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Disease pathogenesis | Indirect health impacts,2020 +C03006,172676,"Capturing the anticipated/unanticipated consequences of COVID-19 (C19) and C19 prevention, management, and treatment strategies (C19PS) among Indigenous peoples (IP) in Arctic communities (AC)","The potential consequences of COVID-19 (C19) spreading in Northwest Territories (NT) and Nunavut (NU) remote and isolated communities are severe due to high rates of chronic conditions, overcrowded housing and limited health infrastructure. The Governments of NT and NU have implemented C19 prevention strategies (C19PS), such as travel bans and social distancing. There is an urgent need to capture and understand the anticipated and unanticipated consequences of C19, and C19PS, as well as on the treatment and management of patients in NT and NU, and gather culturally safe recommendations from and for the communities. In addition, we must document the challenges faced by healthcare professionals, public health and policymakers for future planning and mitigation. Working with 4 NT and 6 NU communities, leadership from Indigenous communities and groups, a Community Advisory Board including Elders, and the research team, this project will work with local community coordinators and local community research assistants to collect information via telephone interviews on the impacts of C19 and C19PS that can, upon analysis and dissemination, immediately be used in policy and planning for current and future pandemics. All data collection materials will be developed and led by communities and local staff will be hired to recruit and undertake the interviews, ensuring capacity building, local employment, and sustainability. The majority of the team are Indigenous and almost all have worked together on Indigenous Arctic projects. The team also includes NU/NT public health policymakers, specialists/experts (mental health, qualitative research, ethics/knowledge translation, C19 pandemic research) and international (USA, Finland, Greenland, and Russia) and national collaborators/ international advisory board members, and therefore results will be relevant for Arctic communities at the community, regional, territorial, national and international levels.",2020,2020,University of Alberta Medicine,1138035,Human Populations,Other | Unspecified,Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Social impacts | Health service delivery,2020 +C03007,172696,Determinants of Community COVID Transmission: Learning from the Hutterites,"Synopsis Achieving a better understanding of the determinants of community transmission of COVID-19 is one of the most important challenges facing governments both in Canada and worldwide. This is best studied in actual communities. To do this, it is critical to understand factors such as the role of children and herd effect in community transmission, the role of pre-existing immunity, and the role of physical distancing. Filling these gaps will go far towards reducing the burden of disease to Canadians and others worldwide. Data and Methods Prospective cohort studies where members of multiple entire cities or towns are enrolled are usually not feasible. To this end, we propose a unique Canadian model. Hutterites, along with the Mennonites, were founded as Protestant sects in the 16th century Anabaptist movement of Switzerland. The majority of Hutterites live in Alberta, Saskatchewan, and Manitoba where they practice communal farming on small colonies relatively isolated from towns and cities. Within these homogeneous, moderately sized colonies, regular respiratory virus transmission is facilitated by a communal lifestyle. We propose to conduct a cohort study on COVID-19 in Hutterite colonies to understand community determinants of COVID-19 transmission. We will examine the role that children play in transmitting COVID-19, the role of physical distancing, the role of co-infection with influenza, and the role of virus strain variation. Impact Findings from this cohort study will inform policy makers about the determinants of community transmission. The study will also give vital information about the role of children in creating herd immunity as well as data on diagnosis, the impact of influenza, and SARS-Co-V-2 strain circulation in communities.",2020,2020,McMaster University Pathology and Molecular Medicine,1111854.75,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Minority communities unspecified,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Disease susceptibility | Restriction measures to prevent secondary transmission in communities,2020 +C03008,172741,A systematic and living evidence and guideline recommendation map on COVID-19,"Under the leadership of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations and Cochrane Canada, this project will support Canada's contribution to the global response to the COVID-19 outbreak by bringing together world-class institutions in prioritizing, conducting and mapping synthesized evidence, and in developing clinical, public health and health policy recommendations to research critical questions of global importance for COVID-19. The aims of this project are to provide efficient, easy-to-navigate, adaptable, and freely accessible quality-appraised COVID-19 evidence and recommendations for different stakeholders. For the first aim, we will systematically identify and critically review and map relevant evidence to support researchers and guideline developers in finding the available relevant evidence to their needs, all in one living evidence map. This work is ongoing in collaboration with the Norwegian Institute of Public Health. The second aim focuses on immediately and longitudinally collecting all trustworthy COVID-19 recommendations and create a platform that allows decision-makers to 1) easily locate specific recommendations and the information that supports it, 2) contextualize these recommendation through the GRADE approach, supported by capacity-building for contextualization by the central team for various jurisdictions, and 3) provide continuous feedback to support the research optimizing the work on the platform. We are unaware of any other research team developing living recommendations in relation to COVID-19 that can be contextualized and allow a centralized collection and provision of evidence about this contextualization from various jurisdictions worldwide. This work highlights the novelty of the two-way iterative interaction among the map, the team, and stakeholders.",2020,2020,"McMaster University Health Research Methods, Evidence, and Impact",1092206.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C03009,172669,Development of an Implementation Framework to Advance Provincial and National Health System Supply Chain Management of the COVID-19 Pandemic,"The COVID-19 pandemic demonstrates the current gap in healthcare supply chain in Canada, as healthcare workers struggle to access the products and equipment needed to deliver safe, timely, and quality care to Canadians. The purpose of this research is to examine supply chain processes and infrastructure to create the evidence for strengthening supply chain infrastructure that ensures that products are available to public health teams and health care professionals to protect the health of every Canadian citizen. The research will conduct mixed-method case studies of seven provinces to document how supply chain processes influence COVID-19 health outcomes, and how data, digital tools and analytics can improve health services and public health efforts to manage COVID-19. Cases will examine policy frameworks that ensure health teams have safe and effective products from quality companies, as well as strategies to support effective federal-provincial-territorial supply chain coordination. This research will inform strategies to ensure Canadians have access to public health prevention initiatives and can access care for those who become infected by COVID-19. The proposed research will advance supply chain resilience across Canada to ensure health system capacity, accelerating Canada's pandemic response, and ensuring public health and health care teams have the products and equipment needed to prevent, detect, treat, and manage COVID-19. Improved supply chain infrastructure will create transparency of the effectiveness of COVID-19 interventions, enabling Canada to better coordinate with national and global supply chain networks and strengthen Canada's capacity to proactively manage COVID-19. Evidence of policy frameworks and supply chain infrastructure informs clinical and health system management of this pandemic and will advance planning and coordination across provincial, federal, and global health systems to support effective and timely management of COVID-19.",2020,2020,University of Windsor (Ontario),1033955.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening","Therapeutics logistics and supply chains and distribution strategies | Vaccine logistics and supply chains and distribution strategies | Policy research and interventions | Other secondary impacts | Health service delivery | Medicines, vaccines & other technologies | Institutional level capacity strengthening",2020 +C03010,172718,A rapid at-home test for SARS-CoV-2,"As governments move toward re-opening Canada, it is critical that we have in place fast and simple tests for COVID-19. Canada needs cost-effective diagnostic technologies that allow for accurate and real-time mass testing in a variety of places, such as homes, airports, doctors' offices, borders, long-term care facilities and remote locations without access to centralized testing facilities. The goal of this proposal is to adapt and optimize existing technologies, originally developed by a team of researchers at McMaster University for bacterial detection, into a rapid point-of-need test for COVID-19. The test targets two classes of unique biomarkers - RNA and proteins - from COVID-19 to increase the test accuracy. It targets the RNA using molecular scissors made of DNA (called DNAzymes) and the proteins using molecular hands made of DNA (called DNA aptamers). These molecular scissors and hands will convert the presence of viral RNA and proteins to a DNA output, which is then massively amplified via an equipment-free room-temperature amplification method, known as ""rolling circular amplification"" (RCA), making the test highly sensitive. The device for the test is very simple and cheap, resembling a home pregnancy test. The test uses saliva as the sample source and fast chemical and biochemical reactions so that the test can be performed easily within 30 minutes by untrained users at home or any other points of need. Test reagents are contained in tablets for user convenience and high stability. Our team has already obtained proof-of-concept for most of the components of the test and will aim to optimize and integrate these components into a test kit, and validate the test by working with clinicians at the frontline of COVID-19 diagnostics and treatment. We are also working with Canadian industrial partners who can help with manufacturing and distribution of tests and recording of test results.",2020,2020,McMaster University Biochemistry and Biomedical Sciences,985562.25,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03011,"172683, 175536, 175581","Evaluating the differential impact of what we have done, as we prioritize what to do next: a multi-provincial intervention modeling study using population-based data [Added supplements: COVID-19 Variant Supplement; COVID-19 Variant Network]","In Canada, as elsewhere, the COVID-19 epidemic has spread at varying speeds and amplitudes across people, places, and time. Early model predictions were dire across the board largely because of limited local data. So early models had to assume that we were all at equal risk, regardless of conditions that can lead to differential risks of transmission (e.g. living in shelters or long-term care facilities) and of severe outcomes (e.g. age, health conditions). Thus, an assumption of homogeneity was at the heart of the ""hammer"" part of the public health response. Public health measures (interventions) also varied between provinces. As we enter the ""dance"" phase and prepare for future waves of the epidemic, we have an opportunity to be more specific with our interventions if we can quickly learn from how well our public health measures worked or did not work for different subgroups and between provinces, using the wealth of data now available. Our team will use an integrated surveillance and health-administrative data infrastructure and mathematical models that were built over the last 2 months in Quebec, Ontario, Manitoba, Alberta, and British Columbia to answer the following questions: 1. Who, where, when, and under what conditions are subsets of the population most at risk? 2. What led to differences in the trajectory and size of COVID-19 sub-epidemics within and between provinces? 3. What types of population- and facility-specific strategies that could stop these sub-epidemics and prevent their re-emergence, while allowing us to relax universal physical distancing measures? Our team of epidemiologists, mathematical modelers, statisticians, clinicians, microbiologists, and public health officials will work together to rapidly provide answers in way that embraces data-driven heterogeneity in risks so that we can better inform decisions on what to implement, when, for whom, and for how long, to minimize the need for universal stay-at-home strategies.",2020,2022,"St. Michael's Hospital (Toronto, Ontario) Infectious Diseases",1070612.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions,2020 +C03012,172628,Imaging COVID-19 Lungs to Uncover Therapies,"The clinical and scientific community are at a complete loss trying to understand what happens inside patients that are infected with SARS-CoV-2. They may have some clotting in blood, some platelet clumping and some inappropriate inflammation but what is causing this is unclear and so right now clinical trials are designed on best guesses on what is going on. If researchers could look inside the patients and had all the different cell types color coded, they would know exactly what is going on. Our team proposes to do this in special humanized mice so they behave much more like humans in response to SARS-CoV-2, in hamsters a natural animal model of SARS-CoV-2 and finally in human blood vessels and human lung organoids which are small versions of real human lungs that can be perfused with human blood from COVID-19 patients or infected directly with SARS-CoV-2. We have stained endothelium, neutrophils, platelets, monocytes, macrophages and NK cells different colors so we can watch using a special intravital microscope what each of these cells do during infections. These are the key responders during an infection and because there is clotting and platelet clumps forming and inflammation, we know that the lining of blood vessels the endothelium is likely involved in this inappropriate response. We will look at whether the immune cells and platelets are interacting to determine whether this leads to hyper-activation of the immune cells leading to the release of many toxic molecules into the blood stream. We have a number of lead compounds that we believe can prevent this from happening. Dr Paul Kubes leads this team of immunologists, virologists, pathologists, ICU doctors and lung specialists. Dr Kubes is one of maybe 2-3 labs in the world publishing on visualizing immune responses in lung infections in living animals and together with the various experts they will unveil the intricate problems SARS-CoV-2 causes and find therapies to cure this problem.",2020,2020,University of Calgary Physiology and Pharmacology,953553,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2020 +C03013,172768,COVID-19: Comprehensive biomarker analysis for prediction of clinical course and patient treatment outcomes (COVID-BEACONS),"The COVID-19 pandemic has taken the world by storm. In Canada alone, there are more than 60,000 confirmed cases and more than 5,000 deaths. Despite its global impact, there are no specific therapies. While most patients display mild or no symptoms, a significant number result in severe disease, and sometimes death. We do not know what causes some patients to die from the infection. Developing a test that can identify patients who are at high risk of severe disease would help save lives. Early clinical reports noted that COVID-19 patients have a high risk of developing blood clots in the body including in the brain and lungs, thus hinting at how it makes people ill. We believe that this likely stems from a severe immune response to being exposed to the virus, SARS-CoV-2. This inappropriate response leads to a vicious cycle of damage to the blood vessels. Therefore, measuring when and how clotting problems develop may allow us to learn how severe COVID-19 disease progresses, find new treatment targets, and identify the patients that need to be treated earlier to prevent progression. To achieve this, we have assembled a collaborative effort between the largest intensive care hospital networks in Canada with the Thrombosis and Atherosclerosis Research Institute (TaARI), the largest and most comprehensive Canadian facility dedicated to the study of inflammation and blood clotting diseases. We will measure biomarkers from the biological pathways that control inflammation, blood vessel integrity, blood clotting, and blood clot breakdown. We will then identify which markers can predict disease progression. By understanding which pathways are disrupted over the development of severe COVID-19 disease, we may be able to identify those patients requiring aggressive therapy earlier in the course of the disease.",2020,2020,McMaster University Medicine,879993.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03014,172644,Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19,"Coronavirus disease (COVID-19) can cause low oxygen levels and life-threatening lung failure. Many COVID-19 patients will need treatment in the Intensive Care Unit (ICU) with life support and a breathing machine. A possible treatment that could stop patients in hospital from developing lung failure is prone positioning. Prone positioning is when a patient lays on their stomach and rests for several hours. The risks of prone positioning in COVID-19 are not known. We designed a clinical trial to test if prone positioning before patients need life support can prevent death or the need for a breathing machine. Patients with COVID-19 and low oxygen levels will be treated with either prone positioning or normal positioning. The clinical trial will be performed at 34 hospitals across Canada, Saudi Arabia, and Mexico. If prone positioning saves patients' lives or prevents the need for breathing machines, it will be used in hospitals across Canada and around the world.",2020,2020,McMaster University Medicine,816903.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2020 +C03015,171602,CRISM Urgent Guideline Activities Related to COVID-19,,2020,2021,Centre hospitalier de l'Université de Montréal (CHUM),750000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",,2020 +C03016,"170344, 171482, 175560",Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2) [Added supplements: COVID-19 Variant Supplement; sex as a biological variable supplement],"An epidemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly in China and 27 other countries. As of 15 February 2020, over 69,000 cases of COVID-19 have been reported, with 1,666 deaths. The enormous health, economic and social impact clearly make it paramount to better understand the pathogenesis of COVID-19, as no specific drugs are available to combat COVID-19. To address this issue we have put together a world-class international research team of basic scientists and clinicians who have a track record of working together and have access to resources [SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",2020,2022,"Keenan Research Centre (Toronto, ON)",834500,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C03017,170724,"Sentinel surveillance, viral shedding, clinical characteristics and outcomes of confirmed and suspected hospitalized cases of COVID-19/SARS-CoV-2 infection in the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance Network","The Canadian Immunization Research Network's (CIRN) Serious Outcomes Surveillance (SOS) Network has been conducting influenza surveillance in Canadian hospitals for the past decade. Currently, the SOS Network includes hospitals across five provinces, representing more than 6,000 inpatient beds. The SOS network is now in a position to contribute to Canada's public health response to the COVID-19 pandemic. Adult patients who are admitted to SOS Network hospitals with suspected COVID-19 illness will be tested for the novel coronavirus as part of their usual care. Patients with confirmed COVID-19 will be enrolled in the surveillance study, meaning that key data about their health will be collected, such as age, sex, chronic conditions, frailty, and COVID-19 risk factors such as travel and contact history. Their health outcomes will be tracked, including the need for treatments such as oxygen therapy, breathing tubes, admission to Intensive Care Units, and survival. A subset of patients will be invited to volunteer for repeated swab testing during the course of their illness to help understand how long people are potentially infectious. All of these efforts will help inform the Public Health Agency of Canada and the scientific community about COVID-19 in Canada and contribute to global efforts to manage this pandemic.",2020,2021,Dalhousie University (Nova Scotia) Medicine,748262.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Health Canada,Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C03018,172764,Long-Term Care in Crisis: The Reality of COVID-19,"Long-term care (LTC) in Canada is in crisis due to the COVID-19 pandemic. To date, 82% of all recorded COVID-19 deaths nationwide are connected to LTC and retirement homes. This research will accelerate the availability of high-quality and real-time evidence to support Canada's rapid response to the global pandemic in order to better manage COVID-19 and position Canada to meet future health threats with particular reference to LTC. The goal of this research is to conduct a thorough examination of the LTC system. The limited capacity of LTC homes in Canada to manage COVID-19 has been emphasized in the media. The challenge facing governments is to understand what went wrong and to create policies that ensure improvements across the LTC sector. The transdisciplinary research team comprises experts in health services, political science, organization and management, finance, health law and health economics, sociology and labour studies. The research findings will provide comprehensive information on critical factors necessary for decision making in LTC. The evidence will provide tangible solutions for multiple stakeholders, including governments, service providers and healthcare workers.",2020,2020,McMaster University,719496,Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C03019,172723,"Population-based seroprevalence of prior infection with COVID-19 in Canada: implications for testing, economic revitalization and population health.","Canadian Blood Services blood donors are healthy people from cities and smaller urban areas in all provinces in Canada except Quebec. Left over blood samples from blood donations will be randomly selected and tested for antibodies to COVID-19. Antibodies are part of the body's response to an infection and are specific for the infecting virus. The presence of antibodies to COVID-19 means that the person previously had COVID-19. They may or may not have immunity to prevent them from getting COVID-19 again (that is, have functional immunity). Over 12 months, 1,500 samples will be tested each month. All samples that test positive for COVID-19 antibodies will have additional testing to measure the antibody concentration (titer) and how effective the antibodies are at binding to COVID-19 virus (neutralization). These will help to understand how likely people who had COVID-19 are to have immunity against re-infection. Tests that can be used for large numbers of samples will be compared to help Canada develop tests suitable for large scale testing. Monitoring functional immunity over the course of the pandemic will help to understand if people start to lose their immunity over time. Monthly data reports will be made available to public health staff (federal and provincial) to inform policy over the course of the pandemic. Mathematical modelling will refine estimates of immunity in the population which is fundamental to public health policy formulation.",2020,2020,Canadian Blood Services (Ottawa),716770.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03020,172742,CODA-19: a Collaborative Data Analysis Platform to Improve Clinical Care in Patients with COVID-19,"COVID-19 is a highly contagious acute respiratory illness that has undergone rapid global spread in the beginning of 2020. There is a pressing need to develop tools that can help physicians diagnose COVID-19 rapidly, determine if different disease presentations warrant different types of treatment, flag patients at high risk of deteriorating, and ensure healthcare resources are attributed efficiently and equitably. Through an established partnership with 9 hospitals, a collaborative analysis platform has been developed to pool data from multiple sites while minimizing the exchange of patient-level information. This collaboration is building on a large database of biological data from patients tested for COVID-19 that is being collected in these hospitals. Risk prediction models will be developed to identify patients at high risk of COVID prior to the availability of definitive testing, characterize distinct disease trajectories, intervene pre-emptively in patients at high risk of clinical deterioration, and make forecasts to plan hospital resources and staffing. The accuracy of predictions will be continuously verified using new cases, which will be identified from different hospital sites in real time. These predictive models will be used to build tools that can help physicians better treat patients with COVID-19, and provide actionable recommendations to support Canada's response to COVID-19.",2020,2020,Centre hospitalier de l'Université de Montréal (CHUM) Medicine,703462.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C03021,"172717, 175522, 175570",Development of SARS-CoV-2 Peptide Therapeutics and Point-of-Care Salivary Diagnostics for Rapid Viral Detection [Added supplements: COVID-19 Variant Supplement; COVID-19 Variant Network],"SARS-CoV-2 (the causative agent of COVID-19) poses a generational threat, with no licensed vaccines or effective therapies to date. Further, the scarcity in reliable diagnostics, especially when testing asymptomatic/mildly symptomatic cases, is of grave concern. Accordingly, our proposal tackles 2 of the 3 research areas of this call, and addresses all 5 objectives, by developing and testing SARS-CoV-2 therapeutics and also prototyping convenient point-of-care (POC) COVID-19 diagnostics with scaling-up feasibility. For the therapeutic arm, we will innovatively design and test peptide disruptors of the SARS-CoV-2 spike (S) glycoprotein interaction with the human ACE2 receptor during viral entry, and other peptide inhibitors of viral-human interactions required for SARS-CoV-2 establishment. These will be tested in vitro using cell-based assays, with promising disruptors validated in SARS-CoV-2 hamster models. In addition, we will screen our in-house synthetic compounds targeting chaperones as potential SARS-CoV-2 replication inhibitors in both cell-based assays and animal models. On the diagnostic front, we will develop new diagnostic solutions for effective detection of even mild/asymptomatic SARS-CoV-2 carriers at home and/or in remote locations. This POC lab-on-a tip technology will specifically detect SARS-CoV-2 peptides from patient saliva, with our clinician collaborators taking the lead in scaling-up both peptide therapeutics and our POC diagnostic device through ongoing coordination with the federal government and Saskatchewan Health Authority. This proposal brings together leading Canadian scientists and clinicians to fulfill our objectives by generating high-quality data to diagnostically and therapeutically accelerate the detection and prevention of COVID-19 and foster nationwide collaborations, with a clear scaling-up path that will refine decision-making across Canadian jurisdictions for effective and timely containment of the COVID-19 outbreak.",2020,2022,University of Regina (Saskatchewan) Chemistry and Biochemistry,808831.2,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +C03022,172645,Advancing a Potent Inhibitor of SARS-CoV-2 3CL Protease into Clinical Trials,"The coronavirus, SARS-CoV-2, has caused COVID-19, a disease that is currently pandemic. The drug GC376 targets an enzyme in the virus that stops its replication. This drug has been used successfully to treat a fatal disease in cats known as Feline Infectious Peritonitis (FIP). FIP is caused by a coronavirus similar to the virus causing COVID-19. This study will move GC376 into phase I human trials on the path to bringing this compound to the benefit of patients with COVID-19.",2020,2020,University of Alberta Medical Microbiology and Immunology,678177,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Phase 1 clinical trial,2020 +C03023,172649,"A Randomized trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among COVID-19 patients in Mumbai, India","The COVID-19 pandemic has an unprecedented scale of spread. There is urgent need for effective treatments, and research has focused on development of antiviral drugs and vaccines. However, since host immune response is a critical determinant of disease severity for life-threatening infections, interventions that modify deleterious host responses (for e.g. immune activation, endothelial dysfunction, micro-vascular injury and pro-coagulant responses) may also play a critical role in decreasing progression to severe and fatal COVID-19. Micronutrient deficiencies, particularly vitamin D and zinc, have been associated with dysregulation of these host responses and may play an important role in COVID-19. Nutritional status is critical especially in older individuals and those with chronic disease including diabetes and cardiovascular disease, in whom COVID-19 is often more severe. While supplementation is important in other infections, there are no well-designed studies on the potential effect of such supplements in COVID-19. In line with CIHR's call for testing therapeutics for COVID-19, we propose a 2x2 factorial randomized trial to examine the effectiveness of vitamin D and zinc supplements as immune-based therapy among 700 patients in Mumbai, India. We will also examine the immunological response to COVID-19 and the effect of the intervention on specific biomarkers of immune and endothelial activation (e.g. Angiopoietin-2) that are independent and quantitative predictors of severity and mortality in other severe infections (e.g. sepsis, pneumonia).",2020,2020,University Health Network (Toronto),665254.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | South-East Asia,,,,Canada,Canada | India,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C03024,172689,"COVID-19 household study to assess secondary attack rates and the proportion asymptomatic, including children","The spectrum of illness associated with ""Coronavirus Infectious Disease 2019"" (COVID-19) due to the SARS-CoV-2 virus varies a lot. Most people experience mild or moderate illness but some experience severe illness requiring hospitalization or resulting in death. Cases without any symptoms (called asymptomatic) have also been reported but how frequently that occurs is hard to know because people with asymptomatic infections are less likely to be seen by a health care professional or to be tested for the virus. Children appear to be less affected overall by the pandemic, but some reports suggest they are more likely to have mild or asymptomatic infections so may also be missed. To get a better understanding of the extent to which mild or asymptomatic infections, including children, contribute to the overall burden and spread of COVID-2019, we propose a household study involving families with children in British Columbia (BC) and Quebec. When the first case in a household is identified, we will actively follow all of the household members for infection over a one-month period. We will measure how many become infected by testing them for SARS-CoV-2 antibodies in their blood at the start and end of the one-month period and by asking them to self-collect respiratory specimens weekly. All household members will complete a daily diary of symptoms so we can compare their test results to their symptom severity, including whether they had been infected without even knowing it (asymptomatic). To study immune responses and viral shedding in more detail, we will also offer a subset of households to participate in more intensive sampling. These findings will clarify the role of asymptomatic infections and children and help public health authorities navigate the next stages of the pandemic.",2020,2020,Centre hospitalier de l'Université de Montréal (CHUM) Microbiologie et maladies infectieuses,644613.75,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2020 +C03025,172761,"Canadian Surveillance of COVID-19 in Pregnancy: Epidemiology, Maternal and Infant Outcomes; Vulnerable populations","The effects of COVID-19 in pregnancy on both the mother and fetus are largely unknown. Our pan-Canadian team has initiated a prospective national surveillance project, led and centrally coordinated in British Columbia, to monitor outcomes associated with COVID-19 in pregnancy. This project will determine the burden of COVID-19 among pregnant women in Canada, as well as maternal and infant outcomes associated with infection, including whether the virus may be transmitted from mother to fetus in pregnancy or post partum. This study will allow Canada to develop urgently needed, relevant, evidence-based recommendations for maternity and pediatric care providers and pregnant women and their families. Data aggregation with international partners will complement global efforts.",2020,2020,University of British Columbia Obstetrics and Gynecology,619025.25,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03026,"172760, 175557","The COVID-19 Ontario Pregnancy Event (COPE) Network: Assessing the impact of COVID-19 in pregnancy on maternal, fetal and newborn health [Added supplement: COVID-19 Variant Supplement]","In order to assess the mother-to-infant and potential vertical transmission of SARS-CoV-2 infection in pregnant women, maternal and neonatal biological samples will be prospectively collected from women with confirmed or suspected COVID-19 at participating hospitals across Ontario. Samples will be tested for the SARS-CoV-2 serology and viral load. The study population will consist of pregnant women with confirmed or suspected COVID-19 at any point during pregnancy, who will be delivering at a participating hospital within Ontario and agree to provide maternal and/or neonatal samples. Outcomes for the study objective will be ascertained through the collection and testing of biological samples from the mother and/or infant. Specifically we will: 1) Assess vaginal mucosa, amniotic fluid, placenta, breastmilk, cord blood and neonatal nasopharyngeal swab for RNA particles of SARS-CoV-2, by ddPCR. 2) Examine the impact of SARS-CoV-2 impact on neonate with respect to serology and viral load, in addition to placenta pathology findings and ddPCR. 3) Assess vertical transmission and the effect of SARS-CoV-2 through placental pathology examina",2020,2022,Ottawa Hospital Research Institute Clinical Epidemiology,625031.42,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis",2020 +C03027,172641,Integrated multi-omic delineation of SARS-CoV-2-dysregulated cellular processes,"As of May 10 2020, there were a reported >4 million confirmed cases and > 285,000 deaths attributed to the novel coronavirus (CoV) SARS-CoV-2, causing the COVID-19 disease. Our understanding of the molecular factors that are responsible for the virulence and the selection of host cells to be infected by SARS-CoV-2 that could explain the emerging variety of clinical symptoms reported in COVID-19 patients is rudimentary at best. All strategies of rapidly developing tools to mitigate this catastrophic SARS-CoV-2 pandemic are fundamentally dependent on us identifying and controlling those proteins that execute the cellular mechanisms critical for SARS-CoV-2 virus to infect and replicate in host cells. We will use a powerful novel tool, called SOMAscan, to rapidly determine how COVID-19 (SARS-CoV-2 coronavirus), and a variety of other coronaviruses, affect large numbers of proteins in different human lung cells, the normal target of the COVID-19 virus. By examining how non-pathogenic, and highly pathogenic, coronaviruses, such as SARS-1, MERS and SARS-CoV-2 specifically and differentially affect cellular proteins, we will learn the unique ways in which the deadly coronaviruses can cause disease. We also will examine how these cellular proteins, and virus infection, are influenced by treatment with a variety of anti-viral agents, some of which are currently in clinical trials, to improve the information gained in these complementary clinical trials. Finally, we also will determine how affecting some of the proteins we identify can impact coronavirus-mediated growth and disease processes. Results obtained in this research will provide vital fundamental information about the molecular replication of the SARS-CoV-2 virus and will form the foundation for more in-depth studies, all of which will pave the way for more effective therapeutic interventions to improve human health.",2020,2020,University of Manitoba Medical Microbiology and Infectious Diseases,592621.5,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C03028,172671,A mixed methods evaluation of risk mitigation measures to address the dual public health crises of COVID-19 and overdose,"The COVID-19 pandemic is occurring alongside the overdose public health emergency in British Columbia (BC) with one escalating the harms of the other. The dual public health emergencies has necessitated the development and implementation of innovative response efforts to promote physical distancing and also mitigate the secondary effects of public health measures on persons who use substances (PWUS). We will conduct a mixed-method study of the risk mitigation efforts introduced to reduce COVID-19 infection among PWUS including prescription of pharmaceutical alternatives (PALS) for opioids, stimulants, benzodiazepines, and other drugs or referral to a managed alcohol program (structured dispensing/delivery of alcohol). Linked administrative health data in combination with survey and interview data collected from PWUS and health care providers will be used to: 1) Determine the impact of PALS on COVID-19 infection; non-fatal/fatal overdose; and continuity of care for SUD and concurrent health conditions among PWUS. 2) Articulate how PALS has affected the uptake of physical distancing and other public health measures introduced to reduce the spread of COVID-19 (e.g., mask wearing, hand washing, self-isolation). 3) Identify barriers and facilitators to PALS implementation based on program uptake and the perspectives of PWUS, outreach workers, prescribers and other stakeholders. This project will focus on assessing the effects of risk mitigation efforts on PWUS with an emphasis on First Nations peoples, persons with criminal justice system involvement and pregnant women. PWUS are more likely to have risk factors for severe acute respiratory syndrome and experience homelessness and income insecurity. This project will provide critical evidence to inform pandemic planning and emergency response activities at federal, provincial and local levels in advance of the Health Canada exemption expiring, expansion of PALS in other Canadian provinces, and upcoming 2020 flu season.",2020,2020,B.C. Centre for Disease Control (Vancouver),583079.25,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Indigenous People | Pregnant women | Individuals with multimorbidity | Vulnerable populations unspecified | Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Michael Smith Foundation for Health Research,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience","Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Policy research and interventions",2020 +C03029,172647,INTERCEPTORs: engINeered ThERapeutiC dEfensive Particles TO SARS-CoV-2,"The cataclysmic threat that viruses pose for human health and predicted by virologists for decades has been made crystal clear by the current COVID-19 pandemic. A huge success in curtailing viral infections has been the development of safe and potent vaccines that confer extended immunity as well as the development of antiviral drugs. Many viruses however evolve rapidly (e.g., influenza A, coronaviruses, etc.) rendering previous vaccinations ineffective and drugs obsolete. We propose the development of a new platform that will convert defective particles, generated by all viruses during infection, into antiviral therapies. Defective Interfering particles (DIs) arise during the propagation and spread of a virus infection and are generated by errors made during viral replication. DIs cannot replicate in the absence of the parental virus due to a lack of essential genes, making them ""parasites"" of the parental virus. Hence, if a DI enters an uninfected cell, there is no infectious virus produced and no deleterious effects on that cell. However, their presence in an infected cell has a profound effect on the replication of wild-type virus since they compete for limiting cellular resources during an infection, thus leading to reduced viral yields and blunting of the infection. Many DIs are also able to induce an antiviral response. There is no published information on the type of DIs that arise during a SARS-CoV-2 infection and how these might impact COVID-19 disease progression - a knowledge gap that these studies will address. In parallel to studies aimed at better understanding COVID-19 disease modifiers, we will also engineer DIs to generate INTERCEPTORs - a new anti-viral therapeutic for the treatment of COVID-19. INTERCEPTORs will be designed from DIs to halt an ongoing infection in progress and significantly decrease disease pathology.",2020,2020,McGill University Biochemistry,558843,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03030,172751,Canadian Longitudinal Study on Aging (CLSA) Covid-19 Study: Understanding the Impact of COVID-19 on Brain Health,"From https://www.clsa-elcv.ca/stay-informed/new-clsa/2020/national-study-collecting-data-aging-adults-experience-during-covid-19 How does a pandemic affect the physical and psychological health of adults as they age? Does COVID-19 have an impact on the delivery of regular health-care services? Does a COVID-19 infection lead to long-term health problems affecting the lungs or brain? These are just a few of the questions a new study being launched by McMaster University hopes to answer. The collaborative research project, conducted in partnership with more than 10 institutions across the country, will examine the experiences of older adults during the coronavirus pandemic, exploring how they cope, the impacts on their physical and mental health, and changes to how they access health-care services. The COVID-19 study is being conducted by the Canadian Longitudinal Study on Aging (CLSA), a national research platform on health and aging involving more than 50,000 participants across 10 provinces. The CLSA is led by lead principal investigator Parminder Raina of McMaster University, and co-principal investigators Christina Wolfson of McGill University and Susan Kirkland of Dalhousie University, along with a national team of researchers. ""By using the rich data from the CLSA to study COVID-19, we can assess which factors appear to protect against or increase the risk of developing symptoms,"" said Raina, a professor in the Department of Health Research Methods, Evidence, and Impact at McMaster and the scientific director of the McMaster Institute for Research on Aging. ""This offers a unique opportunity to understand why some individuals develop severe disease while others remain asymptomatic despite being infected by the virus."" Over the next six months, the CLSA COVID-19 study will collect weekly and monthly data from its participants through online and telephone surveys to gain a comprehensive picture of the spread and impact of the pandemic. In addition to data on health and well-being, the study will also gather information on health behaviours, such as social distancing and handwashing, workplace and economic impacts, as well as travel history. Funding for the CLSA COVID-19 study has been provided by the McMaster Institute for Research on Aging (MIRA), McMaster University and Juravinski Research Institute through a new gift earlier this month for research on the pandemic from Hamilton philanthropists Charles and Margaret Juravinski. The CLSA is a major strategic initiative of the Canadian Institutes of Health Research. Funding for the platform has been provided by the Government of Canada through the Canadian Institutes of Health Research and the Canada Foundation for Innovation. Additional support has been provided by several provinces, affiliated universities and research institutions across Canada.",2020,2020,University of British Columbia,542027.25,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease pathogenesis | Approaches to public health interventions | Indirect health impacts | Economic impacts,2020 +C03031,"172690, 175571","COVID-19's differential impact on the mental and emotional health of Indigenous Peoples and Newcomers: A socioeconomic analysis of Canada, US and Mexico [Added supplement: COVID-19 Variant Network]","Evidence shows that there are economic, and cultural differences in COVID-19 frequency, hospitalization, and mortality (Rodriguez-Lonebear et al., 2020; NYC Health 2020). What is less known is how the restrictions that governments have requested to ""flatten the curve"" may have affected the mental, social and economic health of the population. Recent reports suggest that within populations, there is inequality in how these restrictions have been experienced. For example, job losses are gendered (UN, 2020; Statistics Canada 2020a) and racialized (NPR 2020). Concentrated outbreaks-in meat packing plants, and in long-term care homes have been reported widely in all three countries (Bragg, 2020, Reuters 2020). Racialized peoples are also overrepresented in industries where COVID-19 infections are more likely such as food service and manufacturing, hospital and long-term care staff (IOM 2020; Block and Dhunna, 2020). Because the virus preys on people in vulnerable situations such as overcrowded housing and work stations, these conditions are frequent among racialized persons, Indigenous persons and newcomers, our project answers two central questions: 1) How have COVID-19 related government imposed regulations differentially influenced the mental health and well-being of Indigenous peoples, racialized persons and immigrants? And 2) to what extent have socioeconomic inequalities faced by Indigenous peoples, racialized persons and immigrants influenced their experience of COVID-19 and its related social and economic restrictions? Given our connected borders and interconnected cultures and people, we argue that success rests upon our ability as a continent to work together to protect one another and eventually eradicate this virus which necessitates the three country comparison of Canada, US and Mexico. This proposal seeks funding to build on an ongoing weekly Socioeconomic impacts of COVID-19 survey involving over 17,500 Canadians and Americans.",2020,2022,University of Manitoba Sociology,573100.35,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | United States of America | Mexico,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C03032,172643,Semaglutide to reduce Myocardial injury in PATIents with COVID-19 (SEMPATICO): An exploratory randomized controlled clinical trial,"The current COVID-19 pandemic has now affected over 4.1 million people with almost 300,000 deaths. In Canada, there are almost 70,000 cases and over 5100 deaths. There is no decline in the spread of this infection. The virus can cause heart damage in up to 28% of affected patients, with over half of these patients who develop heart damage not surviving their infection. Scientists believe that the virus may cause direct damage of heart cells, or a storm of molecules that cause inflammation, and small blood vessel clots that starve the heart of oxygen. In animal studies, damage is reduced by new diabetes drugs, known as GLP-1 receptor agonists (GLP-1RA) already approved for the treatment of diabetes. Important studies show that GLP-1RA lower the risk of heart attack, stroke and death in patients with diabetes, and that small molecules generated by GLP-1RA directly protect cell of heart blood vessels. The clinical data are so promising with GLP-1RA, that this drug class is now being studied in obese non-diabetic patients at high risk of CV disease. Based on this evidence our hypothesis is that the GLP-1RA semaglutide (Ozempic - Novo Nordisk) will reduce heart damage caused by COVID-19, by protecting heart blood vessels cells. We hypothesize that these effects will reduce the need for patients to need a hospital, a ventilator, and reduce the risk of death. Our target population includes symptomatic COVID-19 patients who are at home or hospitalized, but not (yet) in an intensive care unit (ICU). By random assignment (by chance), they will be assigned to receive a once-weekly simple-to-self-administer painless ""pen-click"" subcutaneous injection of semaglutide or placebo for a total of 4 weeks. We will keep track of how many patients have heart muscle damage, how many need hospitalization, a ventilator to support breathing or medicine to support blood pressure in the ICU, and how many die. We will conduct the study in 15 centres in Canada and other countries.",2020,2020,University Health Network (Toronto) Internal Medicine,498108.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C03033,172684,Serological Testing to Outline Protocols for COVID19 in Inflammatory Bowel Disease: STOP COVID-19 in IBD,"As provinces begin to ease up on physical distancing restrictions, people with inflammatory bowel disease (IBD) who are immunocompromised due to their medications are faced with a difficult dilemma: Do they continue to follow strict isolation protocols until a vaccine is available (possibly more than 18 months), or do they risk potentially severe complications from COVID19-eg. hospitalization or death. At present, we do not know the true risk that COVID19 poses to this population, or if having COVID19 once makes an individual immune to reinfection. This study will follow a cohort of immunocompromised people with IBD for one year to determine infection rates, susceptibility to reinfection, and risks of severe complications from COVID19 by age, sex/gender, pregnancy status, medication type, and disease type (Crohn's disease or ulcerative colitis). As real-world data is accumulated and assessed, we will update Canadians with IBD and their healthcare team with the most up-to-date information available on risk through weekly webinar series and an online interactive dashboard for personal risk assessment. Do immunocompromised people with IBD need to continue strict isolation protocols for the next 18 or more months, and do those who have already had COVID19 need to worry about reinfection? This study seeks to answer exactly these questions through routine blood tests conducted at the time of regular, ongoing treatment so we can provide the best evidence-based advice to patients possible.",2020,2020,University of Calgary Medicine,477562.5,Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03034,172747,Medical Masks versus N95 Respirators to Prevent COVID-19 in Healthcare Workers: A Randomized Trial,"Little is known about the effectiveness of respiratory protective devices in protecting healthcare workers from 2019 novel coronavirus disease (COVID-19). Epidemiologic data to support the superiority of an N95 respirator, preferentially recommended by U.S CDC and European CDC for prevention for COVID-19, over the less expensive and readily available medical mask, are sparse. In contrast, the World Health Organization and the Public Health Agency of Canada (PHAC) recommend use of a medical mask for the routine care of patients with COVID-19. As the pandemic has evolved, a serious concern has been that there is not a sufficient stockpile of N95 respirators available for aerosol generating procedures. Moreover, compliance with N95 respirators could overtime decrease as they have been associated with headaches and discomfort. This could lead to a lack of compliance, which during SARS increased the risk of infection. Although for aerosol generating procedures, N95 respirators are the preferred method of protection, for non-aerosol generating patient care, it is not clear that N95 respirators offer greater protection than medical masks based on the two small existing observational studies that addressed this. Furthermore, the requirement for fit testing may be a barrier in low and middle-income countries. It is therefore of prime importance during this pandemic to conduct a head-to-head comparison of medical masks and N95 respirators. For this reason, we propose a randomized controlled trial in which healthcare workers in healthcare facilities in three provinces will be randomized to either medical masks or N95 respirators when providing care to patients with COVID-19. We will detect confirm COVID-19 in both groups. We hypothesize that medical masks offer similar protection for routine care than N95 respirators for COVID-19.",2020,2020,McMaster University Pathology and Molecular Medicine,468714.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +C03035,"172765, 175500",SARS-CoV-2 immunization strategies to enhance protective immunity with reduced risk of antibody-dependent enhancement (ADE) [Added supplement: COVID-19 Variant Supplement],"A pandemic of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) that emerged from China late in 2019 is currently underway resulting in worldwide severe morbidity and mortality. Thus, a safe and effective vaccine is urgently needed to fight virus propagation. In this project, after identifying and engineering the immunogens, we will translate towards SARS-CoV-2 a versatile, potent and immunostimulating nanotechnology platform recently developed in our laboratory, which not only will adequately present the vaccine materiel to the host immune system but also enhance its immunogenicity, while eliminating the risk associated with the so-called antibody-dependent enhancement (ADE). The gathered investigative team integrates a unique set of complementary knowledge including biophysics, protein engineering, virology and immunology, which is perfectly suited to rapidly address the health challenges of the COVID-19 pandemic, and has the necessary expertise and state-of-the-art infrastructure to conduct the proposed research.",2020,2020,Université du Québec à Montréal Sciences biologiques,512814.32,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03036,172692,Improving the care of older adults living with dementia across Canada during the COVID-19 pandemic: a mixed methods study to inform policy and practice,"Persons living with dementia (PLWD) are disproportionally impacted by the current COVID-19 pandemic. Not only are they at increased risk of severe COVID-19 disease and mortality, they are particularly vulnerable to the consequences of the pandemic including containment strategies (eg. physical distancing) and disruptions in the healthcare system, especially non-COVID care due to 1) difficulty in recalling public health recommendations, 2) disruptions to formal care channels and support networks (e.g. postponed day program, virtual consultation with physicians, shortage of workers and volunteers in home care and community services) and 3) increase isolation, anxiety and depression due to physical distancing measures. Caregivers are also strongly impacted, with increased stress, anxiety and burden. In order to inform policy-makers, health system managers, clinicians, and community organizations, as quickly as possible, we will conduct a study to measure, describe and identify strategies to address the pandemic as well as its consequences in persons living with dementia. We will conduct this study in four provinces (QC, ON, AB, SK), as well as in France. We will leverage our existing infrastructure, expertise and methods to measure the impact of the pandemic and its consequences on health service use, infection rate and mortality in persons with dementia, with data extracted from health administrative databases. We will describe the lived experiences of persons with dementia and their caregivers, as well as family physicians regarding health and social services based on qualitative interviews and surveys. Finally, we will conduct an online deliberative consultation with key stakeholders (persons with dementia, caregivers, clinicians, managers, and decision-makers), to discuss the research findings, share promising avenues, and generate evidence-based recommendations to mitigate the negative impacts of the pandemic and its consequences on persons with dementia.",2020,2020,McGill University Family Medicine,451891.5,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers | Health Personnel | Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03037,"172655, 175551, 175573","Optimizing polar, small inhibitors of a viral cysteine protease to identify a lead for an oral COVID-19 treatment [Added supplements: COVID-19 Variant Supplement; COVID-19 Variant Network]","The COVID-19 pandemic has caused incredible social, personal and economic upheaval and as of early May 2020 killed 275 000 people world-wide and, tragically, is projected to kill millions more. COVID-19 is caused by the SARS-CoV2 (SARS2) virus, which is a coronavirus closely related to SARS. These viruses infect cells and using the host's enzymes and virally encoded proteins create copies of themselves. These viral proteins are different than the host ones and are key targets to stop the viral replication. One such protein for SARS2, nicknamed 3CLP, is key to liberating the viral proteins in order to enable viral replication. Last month compounds we tested strongly inhibited the SARS2 3CLP and were able to inhibit SARS2 replication in a cell-based assay. This proposal is to design and make modifications of those compounds to better inhibit SARS2 and also optimize drug-like properties to discover a Lead compound for the ultimate development of an oral drug to treat COVID-19.",2020,2022,University of Alberta Biochemistry,549227.81,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03038,172713,A central role for the vascular endothelium in COVID-19 pathogenesis,"COVID-19 is a respiratory disease that can lead to a severe lung infection and death in seniors and patients with additional illnesses. Recent studies have recognized severe cardiovascular injury mainly in children and young adults even in the absence of the typical lung disease. Importantly, there are currently no validated vaccines or treatments for COVID-19. Serious and life-threatening cases of COVID-19 involve uncontrolled immune responses. One important part of the immune system's first line of defense is the complement system, which typically helps to clear invaders and damaged cells. Recent studies implicated complement as important in COVID-19, as it is known to activate the inner lining of blood vessels, the vascular endothelium. Endothelial activation leads to the attraction of inflammatory cells, which adds to an ""inflammatory storm"" and increases the risk of blood clotting, together closing a vicious cycle of blood vessel destruction and poor outcome. In a health care system crisis like the current COVID-19 pandemic, identification of patients in highest need for treatment and early determination of likely patient outcomes are urgently needed. We aim to address these needs by (i) investigating the mechanisms, by which complement injures and activates the endothelium, and (ii) identifying the resulting biological markers (biomarkers) reflecting inflammation and endothelial injury, and correlating them with the outcome of COVID-19 patients, thus establishing a COVID-19 risk score. Our study will help to fight the current COVID-19 pandemic in two ways: (i) identifying complement as important mechanism of inflammation and blood vessel injury will allow for trialing available complement blockers in COVID-19 patients; (ii) identifying biomarkers predicting patient outcomes will help determining patients in biggest need for help, and - in a desperate shortage of resources - identifying the ones who might have a chance to survive.",2020,2020,Hospital for Sick Children (Toronto) Cell Biology,437604,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03039,"172677, 175548","Engage-COVID-19: A mixed methods study of biomedical, behavioural, and psychosocial aspects of the COVID-19 pandemic among gay, bisexual, and other men who have sex with men in Canada [Added supplement: COVID-19 Variant Supplement]","Gay, bisexual, and other men who have sex with men (GBM) have historically experienced significant disparities in physical, mental, and sexual health, amplified by systemic marginalization and high barriers to healthcare. This context of inequity creates heightened vulnerabilities to COVID-19. Failure to respond to the health and wellness needs of GBM may have significant negative effects on COVID-19 outcomes and exacerbate existing health disparities. We propose the Engage-COVID-19 Study to rapidly respond to current and pressing knowledge gaps concerning the COVID-19 pandemic among GBM in Canada. This study will be embedded within the Engage Cohort Study, which is the only study with comparable biobehavioural data on HIV/STI prevalence and risk behaviours for GBM in Canada. To date, baseline data collection has been completed with 1842 GBM who are enrolled in the Engage Cohort Study (565 in Vancouver, 388 in Toronto, and 889 in Montreal). All of these participants will be invited to have SARS-CoV-2 antibody testing and complete an in-depth survey that will include COVID-specific quantitative questions. We anticipate recruiting a total sample of 1695-1768 participants. In addition, from this group we will recruit 90 GBM participants for qualitative interviews in Vancouver (30), Toronto (30), and Montreal (30) to assess the direct and indirect impacts of COVID-19 on Canadian GBM. These data are necessary both to understand COVID-19 risks, vulnerabilities, and prevention strategies, as well as the impacts of COVID-19 on health service access and different levels of HIV/STI risk across provinces. By making efficient use of available research infrastructure, our proposed study will ascertain the occurrence of COVID-19 by documenting SARS-CoV-2 immunity within both HIV-positive and -negative participants and produce rapid, high-quality evidence for preventing the direct and indirect effects of COVID-19 for this population across multiple jurisdictions.",2020,2022,University of Toronto,545795.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions,2020 +C03040,172652,Mechanistic studies on ACE2 as a rational therapy for COVID-19,"The COVID-19 pandemic has already killed 100,000s of people worldwide, and triggered a massive global effort to develop vaccines and therapeutics. We will build on our previous research to test a front-line candidate drug, human recombinant soluble ACE2 (hrsACE2), as a treatment for COVID-19. There is a strong rationale for hrsACE2 to be effective: first, hrsACE2 is a modified version of the human protein (ACE2) that SARS-CoV-2 uses to infect cells in the lungs and other organs. We have already shown that hrsACE2 blocks SARS-CoV-2 infection by acting as a decoy. Second, in animal models, hrsACE2 helps to reduce tissue damage in lung, heart, and kidney, and therefore could help prevent multi-organ failure in COVID-19 patients. hrsACE2 is already known to be safe to use, and is currently being tested in clinical trials for COVID-19. While there is an urgent need to understand how SARS-CoV-2 causes disease, evaluate drug efficacy, and optimize treatment conditions, there are limitations to testing in human patients. The goal of our project is to test the effects of hrsACE2 in a living organism and optimize rhsACE2 treatment (dose, drug delivery methods, and timing) to get maximal benefits. For this we will use our novel, improved, mouse model that expresses the human ACE2 gene in the correct location in the lung and other organs, and develops disease after infection. We will also use this mouse to test combination therapies of hrsACE2 with two other front-line drugs remdesivir, an antiviral, and chloroquine, an antimalarial drug. We anticipate that a combination of hrsACE2 treatment with these drugs would allow a reduction in the dosage of remdesivir (known to have liver toxicity at high dose) and chloroquine (heart toxicity at high dose) to a safer range.",2020,2020,University of British Columbia Medical Genetics,433567.5,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C03041,172678,"The Cedar Project: Preparing for culturally-safe, trauma informed COVID-19 response among young Indigenous people who use drugs in Prince George and Vancouver, BC","Indigenous people who use drugs in BC are facing two public health emergencies: COVID-19 and the ongoing overdose crisis. One may create additional risk for the other. On one hand, substance use may increase COVID-19 risk through sharing smoking/injection equipment; creating barriers to physical distancing; and housing instability. On the other hand, COVID-19 and its response may increase overdose risk due to rollback of harm reduction services, banning of guests in social housing, and forcible closure of encampments - pushing people to use drugs alone. Pandemic fears and restrictions may also impact mental wellbeing. Our study assesses the impact of COVID-19 and the pandemic response, as well as its domino effects, among Indigenous people who use drugs. We will also adapt, implement, and determine the feasibility of offering a bundle of strengths-based, wraparound virtual supports using an existing software and weekly text messaging check-ins with trusted case managers. The study will inform a culturally-safe, trauma-informed COVID-19 response among Indigenous people who use drugs.",2020,2020,University of British Columbia School of Population and Public Health,411943.5,Human Populations,Other,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Drug users | Indigenous People,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2020 +C03042,"172746, 175544",CovidFree @ Home: Development and validation of a multivariable prediction model of deterioration in patients diagnosed with COVID-19 who are managing at home [Added supplement: COVID-19 Variant Supplement],"Millions of Canadians are anticipated to be infected with COVID-19 during this pandemic and many more will contract it in ongoing community transmission and/or a possible second wave. The majority of people who test positive for COVID-19 are sent home to isolate. In this population, deterioration of their disease can happen quickly and without warning, and we currently cannot accurately predict the approximately 20% who deteriorate and need hospitalization. From discussions with our patients and patient advisor, we know that people who are isolating at home feel terrified and alone. We need an effective and safe ambulatory care and research strategy for people with COVID-19 isolating at home. We are a team of heath care workers, patients, researchers and computer scientists (WearCOPD.ca; Can-BREATHE.ca) with five years of experience developing and using remote monitoring systems for respiratory disease. We have already built a smartphone application to facilitate the care of people with COVID-19 at home by allowing them to report their symptoms to their physician. With this project, we will expand our system to also include continuous smartwatch-based monitoring of heart rate, respiratory rate, cough, speech and other parameters. Sensor data will provide us with large volumes of objective data and allow us to build accurate real time machine learning models for predicting who needs to go to hospital. We will integrate these models into a dashboard that alerts clinicians of any patients that area getting worse, so that they can be called into hospital. Patients can be reassured that they are being followed thoroughly even though they are at home. Our system will also provide a platform for further research into how to prevent long term sequalae and preserve the health of people with COVID-19 who do not require hospitalization.",2020,2022,"Sunnybrook Research Institute (Toronto, Ontario)",425172.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C03043,"172693, 175498",Wastewater surveillance of SARS-COV2 to enable real-time clinical case-finding in Calgary [Added supplement: COVID-19 Variant Supplement],"We propose to track SARS-COV2 in the wastewater (WW; i.e., sewage) in Calgary, Alberta. The SARS-COV2 virus is excreted in the poop of infected individuals - often before symptoms start. These viruses are no longer infectious, but their genetic material (RNA genomes) can be detected in wastewater samples using molecular biology techniques for RNA quantification. This project will create a pathway enabling mobilized testing of the WW network throughout Calgary. Our project will achieve 3 objectives: 1 develop procedures to collect and analyse SARS-COV2 genetic material in WW samples from regionally diverse parts of Calgary, 2 develop different molecular assays that complement each other and are resilient to the WW chemical matrix, 3 develop genomics and bioinformatics methods for identifying genetic variants of SARS-COV2 in Calgary WW thereby enhancing epidemiological tracking. In Stage 1 we will develop and validate assays with samples from Calgary's three WW treatment plants, accounting for variability in WW chemistry and its effect on molecular biology methods. In Stage 2 we will work closely with Alberta Health Services and City engineers to apply the assays on WW from areas with known active COVID-19 cases to demonstrate proof of principle. In stage 3 we will deploy in real-time sampling teams through the city to collect samples for monitoring new areas where infections are not known to exist, allowing AHS to proactively find and respond to infected people without symptoms. Our team involves AHS, the City of Calgary, engineers, microbiologists, clinicians/public health experts, and University deans from Science, Engineering and Medicine. We will provide real-time, actionable information on SARS-COV2 in Calgary enabling public health officials to perform regionalized case-finding and develop strategies that focus containment efforts in the areas most affected, while minimizing the collateral social and economic consequences of needed public health interventions.",2020,2022,University of Calgary Medicine,418482.5,Viruses | Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +C03044,"172640, 175563",Characterization of Covid-19 infection in rheumatoid arthritis patients- the CoViD-in-RA project [Added supplement: COVID-19 Variant Supplement],"Rheumatoid arthritis is an incredibly diverse disease. The variability observed in clinical presentation, response to treatment and clinical outcomes suggest that the mechanisms activated during the initiation of the disease, are not uniform. Thus, RA offers a unique model to understand how different underlying immune abnormality lead to different outcome when infected with COVID-19. We aim to correlate clinical manifestations, response to treatment and laboratory parameters in order to inform clinical decisions in RA, especially during COVID-19 infection. Patients with recent arthritis will have blood tests (to analyze immune cells and proteins characteristic for RA subtypes) at baseline and at 6 months. Many patients followed in our service have already had these tests (EUPA cohort Dr Boire), and will also be included in our study, distinguishing between subjects who had COVID infection and those who did not develop it. All patients will have COVID-19 serologies and an analysis of their immune cells. This simple approach is original because we will study the different kinds of immune blood cells (not all cells mixed in whole blood) of patients before they have received any medication, as well as after initiating specific RA treatments. We will follow the patients when receiving DMARDs and advanced therapies prescribed to control their disease. We believe that RA heterogeneity could translate into a different susceptibility to the risk of having COVID-19 infection and to the severity of the infection, with a potentially protective effect from certain treatments in some patients. If we can determine which biological profiles or which treatments are associated with a good or bad response to SARS-CoV2, this could facilitate the management of individuals using these drugs for RA or other diseases, and perhaps also help target therapeutic interventions for COVID-19 in any person, affected with RA or not.",2020,2022,Université de Sherbrooke Rhumatologie,409542.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C03045,172769,Real-time evaluation of the deployment of connected technologies and the partnership of care and services in the context of the health crisis related to COVID-19 - the Techno-COVID-Partnership program,"Aux prises avec une crise sanitaire sans precedent, les deux etablissements qui recoivent le plus de patients atteints de la COVID-19 au Quebec, ont decide de mettre en place des innovations sociales et technologiques adaptees a chaque etape de la trajectoire des patients atteints de la COVID-19, du diagnostic a la guerison, afin de reduire l'isolement, maintenir le partenariat entre patients et cliniciens et favoriser la qualite et la securite des soins. Regrouper au sein du projet Techno-COVID-Partenariat, cette recherche permet d'evaluer en situation reelle de soins, comment ces innovations sont implantees, sur quelles dimensions elles agissent et combien elles peuvent couter ainsi que determiner si des facteurs peuvent expliquer certains resultats. Les innovations etudiees portent sur (i) l'apport des applications mobiles pour le maintien des patients nouvellement diagnostiques ; (ii) la conjonction d'appels telephoniques de benevoles pour briser l'isolement et l'utilisation de differentes technologies pour realiser des teleconsultations et de la telesurveillance ; (iii) l'adoption d'un robot compagnon pour divertir et soigner les patients COVID-19 hospitalises avec des troubles psychiatriques ; et (iv) l'accompagnement des patients lors de leur transition et retour a domicile grace a des patients accompagnateurs COVID-19 et une plateforme de telesurveillance. L'evaluation de ces innovations sont une occasion unique de montrer comment les outils de sante virtuels peuvent potentiellement soigner de maniere fiable des milliers de patients sur une courte periode tout en preservant des personnels de sante a risque et en assurant le maintien du lien social et le partenariat. Si les resultats sont concluants, ils permettront d'accelerer leur implantation dans d'autres etablissements (canadiens et a l'international), non seulement pour la COVID-19 mais aussi pour tout autre probleme de sante pouvant beneficier de ces technologies et modalites.",2020,2020,Centre hospitalier de l'Université de Montréal (CHUM),376865.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C03046,"172685, 175532",Household Transmission Dynamics and Vial Load among Asymptomatic SARS-CoV-2 Infected Children [Added supplement: COVID-19 Variant Supplement],"Children have milder disease than adults and many have no symptoms even when infected by SARS-CoV-2. At present, we do not know how likely asymptomatic-infected children are to transmit the infection. Gaining an understanding of this issue is crucial to determining the role children play in transmission and what the risks will be to other children and adults when children return to school. To answer these questions we will enroll children who are brought for care due to non-infectious reasons (e.g. fall, cut, injury, pain) to 20 emergency departments across Canada and the United States. These sites are participating in the CIHR-funded, 57-site, Pediatric Emergency Research Network (PERN)-COVID-19 study, and currently perform screening of select asymptomatic children for SARS-CoV-2. Participating sites will enroll 400 asymptomatic SARS-CoV-2 positive children and 1,200 uninfected children (3:1 ratio of uninfected to infected child). Study aims: 1) Household Transmission Dynamics: Data will be collected regarding exposures and symptoms at baseline and again at 14 days for enrolled children (infected and uninfected) and their household members. Household members who develop symptoms of COVID-19 will be encouraged to have SARS-CoV-2 testing done (if not already) and the results will be obtained. Analyzing and modeling this information, comparing households with transmission versus those without, will help us understand the transmission risk posed by asymptomatic SARS-CoV-2 infected children. In particular this information will inform social distancing policies (e.g. school re-opening) 2) Viral Load Quantification: All SARS-CoV-2 positive specimens will have viral load quantification performed. These results will be analyzed alongside those from aim #1 to determine the relationship with household transmission. Viral load quantification data will also be analyzed alongside symptom evolution data to inform our understanding of the presymptomatic state.",2020,2022,University of Calgary Pediatrics,407498.54,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease pathogenesis,2020 +C03047,172648,Characterization of interferon-lambda 1 as a treatment for COVID-19,"Our immune system reacts quickly upon virus infection to induce multiple types of proteins to inhibit the virus and prevent spread. Unfortunately, in COVID-19 patients, the induction and/or response to one set of antiviral proteins called interferons (IFNs) may be limited. A Canadian clinical trial is treating COVID-19 patients with one type of IFN, called IFN-lambda 1. IFN-lambda 1 strongly inhibits multiple viruses that infect the lung in animal models, including SARS-CoV-2, the virus that causes COVID-19. IFN-lambda 1 has already been shown to be safe and effective in hepatitis virus infected patients, with less side effects compared to another family of IFNs. IFN-lambda 1 will be given to COVID-19 patients and we will use blood samples from the clinical study to investigate immune mechanisms associated with viral clearance. This project will allow us to understand how SARS-CoV-2 and IFN-lambda 1 affect our immune system by examining immune cells and plasma from patients before, during, and after IFN-lambda 1 treatment. We will also gain knowledge about how SARS-CoV-2 counteracts our natural defenses, and whether there are ways to predict how well people respond to this particular therapy. Ultimately, we believe the results of our study will be very important for not just therapy of COVID-19 patients, but also against other deadly viruses that emerge in the future.",2020,2020,University of Alberta Medical Microbiology and Immunology,374831.25,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C03048,"172701, 175574","Detection and quantitation of SARS-CoV-2 in wastewater to conduct surveillance on burden of community infection, identify outbreaks and support public health decision-making on control measures for transmission of COVID-19 [Added supplement: COVID-19 Variant Network]","COVID-19 has been sweeping the world for 6 months. The daily report about new cases, associated deaths and recoveries globally are mentally traumatic for everyone. However, the real number of people infected by this new coronavirus (SARS-CoV-2) may be far higher than official reported because current testing positive numbers counts only sick patients but not asymptomatic ones. Asymptomatic person is the most dangerous silent source for community transmission. A modeling study suggested that the virus might simmer around the world, triggering epidemics every few years. Thus, it would be important to predict the next wave of virus, which allows the government and people to be prepared. Recent studies have detected SARS-CoV-2 in stool as well as raw sewage. We also detected this virus in sewage collected from three different wastewater treatment plants (WWTP) in Alberta. It has been proposed that the occurrence and levels of SARS-CoV-2 in sewage will mirror temporal burden of community infection. Therefore, the aim of this study is to develop a reliable method to detect the prevalence of community infection and forecast the next wave of COVID-19 through monitoring SARS-CoV-2 in sewage. This will provide evidences on the presence and levels of virus in our community, when it will possibly flare up causing an outbreak, and when and why our health authorities give an order to applying or relaxing social distancing and masking measures for controlling virus spread. A mathematical model based on the results obtained from this study will be generated to predict the trend of community infection under different conditions. This research brings benefits and knowledge to every Albertan, and also give us a tool and measure against new coronavirus now and in future.",2020,2022,University of Alberta Laboratory Medicine & Pathobiology,438064.22,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +C03049,172661,Youth mental health and substance use in the context of COVID-19: A rapid response multi-component program of youth-engaged research and action,"There is minimal research on mental health and substance use (MHSU) among youth during pandemics, limiting our ability to meet the needs of youth. COVID-19 presents a time-sensitive opportunity to rapidly enhance knowledge about the impacts of a public health crisis on MHSU among youth, reduce negative impacts and amplify coping strategies, and improve readiness to respond to future pandemics. This project addresses these challenges in four ways. 1) A survey will be conducted to rapidly understand how COVID-19 is affecting youth MHSU over time, how youth are coping, what challenges they have overcome, and what public health response strategies they recommend. We have already surveyed 622 youth and produced preliminary results; funding will enable us to track the experience of these youth for a year. 2) We will conduct interviews with youth over 9 months to further understand impacts over time. 3) Based on each wave of findings, we will partner with our Youth Engagement Initiative to develop innovative materials and interventions to address expressed youth needs. 4) We will conduct participatory action research summits in Ontario and British Columbia to mobilize the perspectives and voices of youth with MHSU concerns to examine youth-designed pandemic response materials, plan for future pandemic responses, and collect any further insights about the pandemic's impacts. This rapid-response study provides high-quality, real-time evidence to support the management of youth MHSU impacts of COVID-19 via a patient-oriented research approach. By collecting and immediately responding to youths' recommendations regarding the clinical, health, and public health responses that would be most meaningful to them, this study will inform MHSU pandemic decision-making and planning within Canada.",2020,2020,"Centre for Addiction and Mental Health (Toronto) Children, Youth and Families",358417.5,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03050,172733,Impact of COVID-19 on Patients Receiving Hemodialysis: The Quebec Renal Network (QRN) COVID-19 Study,"There are 24,000 Canadians living with kidney failure who must receive regular hemodialysis treatments to stay alive. This involves coming to the dialysis unit 3 days every week, for 4-5 hours at a time. While this is burdensome at the best of times, the COVID-19 pandemic has made life even more difficult for hemodialysis patients. As they cannot self-isolate, they are at higher risk of infection than others. If they do get infected, this may not be easily identified because they may not have typical symptoms or may deny them for fear of being denied dialysis. Yet, due to their underlying medical illnesses, dialysis patients are at risk of becoming quite ill from COVID-19. The precise risks to their health are uncertain. Finally, widespread application of infection control measures in dialysis units and physical distancing, while needed to control spread of COVID-19, may have unforeseen impacts on all hemodialysis patients. These range from encountering problems with transportation, interfering with their critical need to get to the dialysis unit, to their interactions with the health care team, access to non-dialysis health care, and inability to have their loved ones at their bedside during dialysis. Being the province hardest hit with COVID-19, we have established a province-wide team of kidney doctors and other experts in Quebec to study: (1) the infection control measures implemented in each dialysis unit; (2) how to better identify dialysis patients who have COVID-19; (3) their risk of dying from COVID-19 and the longer-term risk of COVID-19 on their physical and mental health; (4) whether they develop antibodies to this infection; and (5) how all dialysis patients have generally been affected by this pandemic with respect to dialysis and non-dialysis medical care. The results of this comprehensive study will guide our understanding of the impact of COVID-19 on dialysis patients in order to help improve their care both in Canada and globally.",2020,2020,Research Institute of the McGill University Health Centre Medicine/Nephrology,357249.75,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Secondary impacts of disease, response & control measures",Immunity | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences | IPC in health care settings | Indirect health impacts,2020 +C03051,172665,Developing strategies to support First Nation communities' decision-making during COVID-19 outbreaks,"Although Manitoba First Nation (FN) reserve communities have yet to experience a positive COVID-19 case, communities are preparing for disproportionate severe outbreaks, based on the experience of H1N1. The COVID-19 pandemic highlighted the importance of modeling in estimating the course of the infection over time, the potential impact of public health measures and the resources required to meet response needs. We developed this proposal at the request and in full partnership with the First Nations Health and Social Secretariat of Manitoba (FNHSSM). We are a seasoned team of FN organization-based and university-based researchers with a long history of collaborating. We are already working together on a number of projects, and many of us worked together on the H1N1 pandemic. For this project, we plan to, 1.Construct/update detailed community profiles of Acute Respiratory Infections, community size, remoteness, access to health care, risk factors associated with severe COVID-19 infection, and local infrastructure limitations impacting communities' ability to respond (safe drinking water, crowding, existing facility to be used for isolation), to support FN-centric model developments; 2.Develop a FNHSSM-based agile platform, for modeling community pandemics, to be updated with live data. Models will be developed with data from community profiles, evidence of transmission and severity derived from the literature and approaches co-created through knowledge exchange via a series of monthly meeting; and 3.Estimate the potential financial and social burden on FN communities, in view of ensuring adequate resourcing to support local responses; We have mobilized FN leadership, modeling, health services research and health economic expertise to support FN planning and decision-making on COVID-19 management in their communities and at the provincial level. Our unique project will strengthen an existing platform and make scalable to other Indigenous contexts.",2020,2020,University of Manitoba Community Health Sciences,356877,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Approaches to public health interventions | Community engagement | Policy research and interventions,2020 +C03052,172754,A Rapid Research Platform to Inform Prevention and Improve the Clinical Management of COVID-19 Illness for Priority Older Adult Groups: The Ontario Multi-Regional Hospital Coronavirus Registry (COREG),"Older adults are the more vulnerable to developing COVID-19 and its complications, particularly home care and retirement home residents. Older persons are also less likely to regain full functional and health recovery after a COVID-19 illness. We have little information on why some people develop severe COVID-19; and how COVID-19 may affect older adults in Canada. There is no information on the medium- and long-term outcomes in survivors and how we can improve their recovery rate and prevent health and functional loss. Rapid large-scale Canadian data platforms, with detailed information on patients with COVID-19 and their clinical course, are needed to address these questions and help plan strategies that can limit the spread and the impact of COVID-19 in older adults now and in the future. We are launching the Ontario Multi-Regional Hospital Coronavirus Registry (COREG), a platform that collects detailed case data on confirmed COVID-19 inpatients, and outpatients, in collaboration with the World Health Organization. We will address these critical gaps, with linkage to provincial data to identify risk factors for severe COVID-19 and death in older adults in the general population, home care, and retirement homes in Ontario. The COREG platform will document the clinical course to 9 months, to study the functional recovery and the need for targeted rehabilitative treatments. COREG will provide rapid high-quality evidence to improve the prevention and clinical management of COVID-19 for older adults in Canada, and internationally. COREG will also provide researchers and partners with complete and in-depth regional and individual-level clinical data on COVID-19 to inform rapid decision-making and projections, sub-studies, extensions, and linkage for all affected populations.",2020,2020,"McMaster University Health Research Methods, Evidence, and Impact",346586.25,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C03053,172694,Public Health Response to COVID-19: Addressing Financial Strain-related Health Impacts of the Pandemic,"CONTEXT: The COVID-19 pandemic is having a devastating effect on people's health. Also because of COVID-19, people are facing unprecedented levels of financial strain due to the economic market collapse, job loss, social isolation, illness, and increased caring duties. Financial strain is the feeling of being unable to make ends meet. It occurs when people cannot pay their bills, feel worried about money, and experience negative impacts on their quality of life and health. Adults under financial strain are at higher risk of depression, anxiety, work absenteeism, and poor physical health. Their children are prone to loneliness, depression, poor mental health, and disability into adulthood. The COVID-19 related public health response to financial strain will be vital now and for societal recovery. PURPOSE: Our team will develop a public health framework on financial strain, as well an indicator tool-kit relevant to diverse settings and groups. This research is focused on the consequences of the sudden collapse of a system as a result of the COVID-19 pandemic. Our findings could also help offset financial strain during other public health emergencies. APPROACH: This proposal builds on our previous work on financial strain. We propose a multi-method comparative study, organized as four parts, and occurring in Canada and Australia. Part 1 involves a rapid realist review and international environmental scan to community-led and government strategies to address financial strain and health impacts. We will also do a policy review of government policies on COVID-related financial strain. Part 2 is interviews with government representatives (multiple levels) and organizations addressing financial strain. A financial strain framework will be developed from Parts 1+2. Part 3 will identify relevant indicators to guide action and lead to a tool-kit for practitioners. Part 4 is the involvement of two Practice Advisory Committees (CDA and AUS) in all project activities.",2020,2020,University of Alberta,336917.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Economic impacts,2020 +C03054,172726,Diagnosing the onset of severe Covid-19 disease,"A recent report from China has indicated that many or most individuals who die from severe Covid-19 infections have sepsis. Sepsis is broadly defined as an abnormal host response to infection that causes life-threatening organ dysfunction, and was responsible for 19.7% of global deaths in 2017. Sepsis is a very complex disease, consisting of phenotypic clusters of patients, that constitute distinct endotypes, which are biologically driven and relevant to clinical outcomes. We have defined 5 sepsis endotypes in a large clinical study and propose to extend this here to severely ill Covid-19 patients. We will collect blood from up to 200 patients in BC and Quebec, and analyze the genes that are expressed in these cells (which will enable us to discriminate endotypes). This will allow us to define a set of genes for which the levels of expression correlate with future disease severity. This information will allow the development of a diagnostic that will enable a physician to predict the likely severity of a patient's disease and apply knowledge-driven clinical management. Furthermore, since endotypes operate under distinct mechanisms this knowledge will enable the discovery, by others, of targeted therapies to treat Covid-19 associated sepsis.",2020,2020,University of British Columbia Microbiology and Immunology,316563,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03055,"172771, 175531",Development of safe and effective vaccines against COVID-19 [Added supplement: COVID-19 Variant Supplement],"The current COVID-19 pandemic is a worldwide threat. Moreover, the ability of asymptomatic carriers to transmit the disease is making it very difficult to contain and control. As such, safe and effective vaccines against COVID-19 are urgently needed. The goal of this research project is to develop effective vaccines to combat COVID-19. Combining our expertise in coronaviruses, vaccine development and viral vector engineering, we plan to take novel approaches to develop highly effective vaccines against COVID-19. We will use a helper-dependent adenoviral (HD-Ad) vector to deliver antigens and we will also generate a bacterium-based BCG-COVID-19 compound vaccine. The HD-Ad vectors that we will use offer several advantages over the conventional Ad vectors: 1) they are safer for human use and potent in the delivery of specific antigens, 2) they have a large DNA carrying capacity for expressing multiple antigen genes without the expression of non-specific antigens from the vector and 3) they produce antigens in their native folded form with proper glycosylation and may not require boosting. BCG is an attenuated bacterium and the approved vaccine against tuberculosis in humans. In addition to its specific immune protection against TB, BCG has non-specific benefits as it prevents about 30% of infections with pathogens including viruses. We will construct a recombinant BCG that secretes a fusion protein composed of the bacterial protein antigen 85A fused to the SARS-CoV-2 RBD. This recombinant vaccine will not only retain BCG's nonspecific anti-viral benefits but will also produce specific immune protection against COVID-19. The success of this project will allow us to proceed with the production of the clinical grade vaccines for further testing clinically more than one vaccines while establishing a collaboration with a Canadian biotech that can oversee the licensing and large-scale production of this vaccine for the Canadian market.",2020,2022,University of Toronto Molecular Genetics,343532.59,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C03056,172763,Utilization of an Existing Longitudinal Observational Cohort of Community Adults to Characterize the Mental Health and Substance Use Impacts of COVID-19,"The COVID-19 pandemic is causing historic disruptions worldwide. Previous epidemics have increased mental health problems and evidence of such impacts is already present in China. Thus, there is a high need to characterize the impact of COVID-19 on mental health in Canadians to ""flatten the mental health curve."" To address this, we propose to examine the impact of COVID-19 on mental health in an existing longitudinal observational cohort of 1502 community adults. This group has been assessed over four waves to date, three prior to COVID-19 and one during COVID-19. Leveraging these existing pre-pandemic and intra-pandemic data, we will ascertain the pandemic's effects on high-priority areas of mental health and substance use. Specifically, we propose four primary aims. The first and second are to examine the impacts on mental health symptoms (depression, anxiety, and posttraumatic stress disorder) and substance use (alcohol, cannabis, tobacco, and illicit drug use), respectively. The third aim is to examine the mechanisms by which these effects arise, including impacts of the pandemic and interrelationships among mental health and substance use. The fourth aim is to address where vulnerabilities exist by identifying high-risk and high-resilience subgroups within the larger cohort of individuals. We will also pursue two secondary aims, including sex/gender differences (separately) and targeted qualitative interviews of individuals exhibiting high-risk or high-resilience profiles. Our findings will be informed by Knowledge Users including a clinical psychiatrist, a clinical psychologist, and leaders from the Mental Health Commission of Canada, the Canadian Centre on Substance Use and Addiction, and Veterans Affairs Canada. Collectively, the research will provide a critical longitudinal perspective on the mental health impacts of COVID-19 that will provide substantive insights for government and healthcare responses in Canada and beyond.",2020,2020,McMaster University Psychiatry & Behavioural Neurosciences,311338.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Vulnerable populations unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2020 +C03057,172736,Improving Canadian Outcomes Research On the Novel SARS-CoV-2 using Analytics: the CORONA Consortium,"Despite the major impacts of Covid-19 on all of society and medicine, relatively little is known about this disease. Early reports indicated that those with cardiovascular disease and its risk factors, may be at higher risk of Covid-19 infection. However, there have been few studies of populations of people who are at risk of, or have developed, Covid-19. In this proposal, we will study people living in Ontario and Alberta, and examine the following important questions. First, we will determine who in the population is at risk of developing Covid-19 infection. We will also determine the factors that influence prognosis, among those who have developed a positive test for the virus. We will do this by using methods of artificial intelligence, called machine learning, and sophisticated statistical techniques to consider the very large electronic datasets that have accumulated over each person's lifetime. Second, we will evaluate if medications that have been used to treat people with conditions such as hypertension or diabetes can predispose to the development of Covid-19 infection. Alternatively, we will determine if some medications may potentially reduce the risks associated with Covid-19 infection. These analyses will be performed by linking the large databases described above with prescription drugs that have been prescribed to people in Ontario and Alberta. Finally, we will determine the impacts of the major changes in healthcare that were instituted as a response to the pandemic. Specifically, we will determine if the changes to healthcare had unintended collateral effects on those living with chronic cardiovascular conditions, such as hypertension, coronary artery disease, and heart failure. We will focus on whether there was an increase in death rates and concomitant changes in hospital visits in people living with these conditions.",2020,2020,University Health Network (Toronto) Medicine,306884.25,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures","Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Indirect health impacts",2020 +C03058,172740,PUPPY Study - Problems Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year: A Longitudinal Mixed Methods Study with Rapid Reporting and Planning for the Road Ahead,"The majority of health care visits are to primary care providers such as family physicians, nurse practitioners, and pharmacists. These individuals make up the core care team for most people. They normally help coordinate and manage health care. COVID-19 has caused significant changes in primary care. In Canada, many walk-in clinics and family practices have closed. Pharmacies remain open but with restrictions on patient interactions. Other major changes in care (e.g., virtual care, reduced referrals) have been made to respect public health and emergency orders. During these times with significant restrictions, patients can be unclear or unaware of how to get the right care, at the right time, from the right provider. Patients also fear getting COVID-19 and avoid care settings. Some will also avoid seeking care for COVID-like symptoms due to fear and a lack of access to a primary care provider. Understanding the rapid changes in primary care and how to navigate these is challenging for everyone, but more so for people without a regular primary care provider to help guide them. This is especially true for vulnerable groups (e.g., those with serious mental illness) and those with chronic health conditions that require ongoing, frequent care (e.g., bloodwork, scans, medication changes). COVID-19-related disruptions may lead to significant delays in treatments or unmet health care needs for many people. This may negatively affect population health outcomes and increase costs to health and social systems. The proposed study builds on existing research with an experienced team. The team will work to understand critical gaps in primary care access and coordination by comparing data from before, during, and after the pandemic. Multiple sources of data will be used such as policy makers, primary care providers, patients, waitlist data, healthcare billings, and prescribing data. The results are critical for strengthening primary care during and beyond the COVID-19 pandemic.",2020,2020,Dalhousie University (Nova Scotia) Family Medicine,305664,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Health service delivery,2020 +C03059,172674,Indigenous Health Counts in Urban Homelands: Estimating COVID-19 Incidence and Mortality among Indigenous Populations Living in Ontario Cities,"First Nations, Inuit, and Metis peoples face many challenges as a result of the COVID-19 pandemic. Due to existing social factors such as poor quality, overcrowded housing, homelessness, and lack of clean running water, infections like COVID-19 can spread quickly. There are also big gaps in data about how COVID-19 is spreading among Indigenous peoples, especially in cities. To address this, we will use information from existing studies about the health of Indigenous peoples living in cities to learn more about COVID-19 spread and it's impacts. The Our Health Counts Toronto, London and Thunder Bay studies used social networks to find Indigenous community members living in these cities. These studies were done by the Indigenous community for the Indigenous community. Our methods allowed us to gather information about the needs of the entire Indigenous populations in these cities, even those who don't use services regularly. By linking the Our Health Counts studies to the provincial COVID-19 database at the Institute for Clinical Evaluative Sciences (ICES), our team will use new statistical methods to accurately estimate the rate of COVID-19 transmission for Indigenous peoples in these cities. We will also check for increases in mortality rates, due both to COVID-19 itself and gaps in access to health care for acute (e.g. heart attack) and chronic (e.g. diabetes) health conditions. In partnership with Indigenous community health services, our research team will improve statistical methods and produce currently unavailable information regarding the burden of COVID-19 and its rate of spreading through the urban Indigenous communities living in Toronto, London and Thunder Bay, Ontario. This information is important as Indigenous Peoples are highly mobile between urban areas and First Nations reserves, and rural and remote Metis and Inuit communities. Improving our understanding of COVID-19 in urban centres can reduce its risk of spreading within and from these cities.",2020,2020,"York University (Toronto, Ontario) Kinesiology and Health Sciences",296595,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Indigenous People,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C03060,172774,"The Response of Provincial Health Systems to COVID-19: Service Provision and Costs Across Health Sectors, First Nations and other populations","The COVID-19 global pandemic has affected not only health, but also health systems. In Canada, cancer surgery, joint replacements, angioplasties and other procedures have been delayed or cancelled. Changes have occurred across the health system. Patients too have adapted, avoiding care out of personal fear of COVID. These unprecedented changes have not been measured yet. In our study, we plan to measure, in British Columbia and Ontario: - health resource utilization and medical costs for patients with mild, moderate, and severe COVID. -how hospitalizations, physicians services, home care, long term care, and other resources have changed in patients without COVID through the COVID epidemic. In particular, we are interested in the effects on women and men, remote regions of British Columbia and Ontario, and First Nations peoples. We will conduct this study using data from British Columbia and Ontario that describe almost every interaction with the health system. This allows us to have a ""population level"" look at the health system as a whole. IMPLICATIONS The pandemic is not over yet. We must plan for recurrence, and think about how it will affect other countries who have not yet borne the brunt of infection. Our estimates of COVID costs will be very useful to health modelers who are trying to help develop public policies such as introduction and relaxation of social distancing. Also, looking at health systems as a whole will allow us to plan for system stresses related to COVID resurgence and future pandemics, and ensure that we can meet the needs of Canadians even under conditions of health system strain.",2020,2020,University Health Network (Toronto) Toronto General Research Institute,295314.75,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Indigenous People | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C03061,172699,"The Anatomy, Determinants and Impacts of the Cargill COVID-19 Outbreak Among Newcomers and their Families in Canada","Alberta Occupational Health and Safety has reported that the High River Cargill Meat Processing Plant did not engage workers or their representatives in its investigation of Canada's largest single-site COVID-19 outbreak. With nearly 1600 infections, this outbreak makes up a quarter of all the COVID-19 infections in Alberta to date and is the largest COVID-19 outbreak cluster in North America. Our health project will study: 1) How the outbreak spread?; 2) Why it spread? and; 3) What was the response? To do this, we will work closely with the Alberta Health Services Public Health team, healthcare workers and social services that responded to this outbreak. We will also work closely with the UCFW Union Local 401, engage community members and work with Cargill employees to do this proposed research. Our embedded mixed-methods case study will collect and share all health-related data and stories from Cargill employees and their families to understand why this rapid outbreak occurred and understand how it affected these workers and their families. This work will advance our understanding of how the outbreak began, what factors led to its rapid spread, and why it affected mostly new immigrant, refugee and temporary foreign worker (newcomers) employees and their communities. The ongoing COVID-19 response and future Canadian public health responses require a detailed investigation to prevent similar outbreaks and create knowledge the public health, healthcare and social services systems need to improve care and community trust during COVID-19 outbreaks.",2020,2020,University of Calgary Medicine,273684.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Community engagement,2020 +C03062,"172642, 175499",Development of small interfering RNAs (siRNAs) for the treatment of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) [Added supplement: COVID-19 Variant Supplement],"SARS-CoV-2 is responsible for the current coronavirus disease 2019 (COVID-19) pandemic for which there are no treatments yet available. We propose to rapidly design and test several drugs that could be delivered intranasally to treat SARS-CoV-2. We will also analyze the immune response to the virus in patient cells to determine a possible correlation between the early response and the outcome of the disease. The technology we will use is called RNA interference and it works by using what are called small interfering RNAs (siRNAs). siRNAs can direct a person's existing RNA interference machinery to attack any harmful RNA sequence such as the RNA genome of SARS-CoV-2. Furthermore, by reducing the viral burden, siRNAs could contribute to mounting a patient's natural immune response to the virus. We will also design siRNAs to target any factor that would prevent the immune response in the early phase of the disease. siRNAs are easy to design, manufacture and are stable for long-term storage and transport. An advantage for their use as therapy for respiratory infections is that they remain in the lungs when administered intranasally and therefore have low potential to cause side-effects in other parts of the body. We expect that from our project we will identify a safe and effective treatment that could be used in the fight against the current pandemic and future outbreaks of related coronaviruses.",2020,2022,Lady Davis Institute for Medical Research (Mtl) Medicine,313386.52,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C03063,172772,MOIST study: Multi-Organ Imaging with Serial Testing in COVID-19 infected patients,"The novel coronavirus has devastated the world since its initial outbreak in Wuhan, China in December 2019. Many individuals with this illness suffer from severe respiratory disease however there is growing evidence that this virus also affects other organs. Many patients with coronavirus disease (COVID-19) have evidence for heart damage during their infection and/or they have reported decreased taste and smell. We have developed new techniques in MRI to image the heart, lung, brain and liver. We are proposing to perform MRI scans on patients hospitalized with COVID-19 in order to better understand the injury to the lung and other organs. We will scan patients within the first 2 days of their hospital stay, at discharge and then 3 months after they are discharged. These three time points will also provide information on recovery from illness, an area which is also not well understood and poorly studied. We hope that this research will better identify patients at long-term risk of health issues from COVID-19. This MRI approach could also be used in future studies to evaluate the effects of new treatments on the lungs and other organs.",2020,2020,University of Alberta Medicine/Cardiology,256776.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +C03064,172675,Utilizing Health System Data to Respond to COVID-19 in Seven Resource Poor Countries,"Michael Law, director of the Centre for Health Services and Policy Research and professor in the UBC School of Population and Public Health, is receiving $341,941 from CIHR to co-lead a study aimed at reducing the impact of COVID-19 in resource-poor countries. Working with Partners In Health, the researchers will use health information systems to monitor for potential COVID-19 hotspots and monitor changes in health services use in Haiti, Lesotho, Liberia, Malawi, Mexico, Rwanda, and Sierra Leone. This data will be used to help inform national public health responses to mitigate the spread of COVID-19.",2020,2020,University of British Columbia Centre for Health Services and Policy Research,256455.75,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Haiti | Lesotho | Liberia | Malawi | Mexico | Rwanda | Sierra Leone,Epidemiological studies | Health Systems Research,Disease transmission dynamics | Health service delivery,2020 +C03065,172700,Vaccination in a pandemic: The impact on routine vaccinations and future COVID-19 vaccine acceptance,"Canadians are asking: During the pandemic, should my children or myself receive our regular vaccines? Is it safe to go to my vaccination appointment? Could COVID-19 make me seriously ill? Will new COVID-19 vaccines be safe, since they are being made so quickly? Will there be enough COVID-19 vaccines for everyone? Like everyone else in the world, Canadians face many concerns about COVID-19, and Canadian health care systems are grappling with the direct and indirect impacts of the pandemic. Physical distancing measures that have been put in place to reduce spread of COVID-19 have led to challenges in providing, and accessing, routine vaccines for all ages, such as those for measles or meningitis. At the same time, one of the primary options for containment of the pandemic is through future COVID-19 vaccines. However, public acceptance of COVID-19 vaccines is already being questioned in the media, and initial vaccine shortages will require prioritization of who receives the vaccine first. An understanding of Canadians' acceptance of future vaccines and their perspectives on vaccine prioritization will be critical before vaccines are rolled-out. The aim of this project is to support the public health system in these tasks. We will begin by assessing how provincial and territorial health systems are delivering routine vaccinations during the pandemic, examining what the public think about routine vaccines during this time, and then measuring whether less/more people are getting vaccinated with routine vaccines during the pandemic. Second, since population support for a vaccination program is critical to its success, we will examine public acceptability of new COVID-19 vaccines and the determinants of acceptability. The project will provide Canada's public health system with essential information to organize the distribution of routine vaccines during the pandemic and to prepare for the inevitable COVID-19 mass vaccination program that is on the horizon.",2020,2020,University of Alberta,251181,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2020 +C03066,172697,"A Distinction-Based Study on Equity in COVID-19 Testing for Manitoba First Nations, Metis and Inuit","Some groups of Canadians are likely to be harder hit by the COVID-19 pandemic than others. First Nations, Metis and Inuit (FN/M/I) Canadians are one example of these. These groups have high rates of chronic illnesses (like heart disease and lung disease) that put them at high risk for poor COVID-19 outcomes. Many FN/M/I people experience poverty and live in over-crowded houses, making it hard to keep physically distant from others. As well, health and social services in FN/M/I communities are often underfunded. This means they may not be able to respond quickly to a health crisis if one occurs. To help prevent this type of crisis, this project will provide data on who is being tested for COVID-19, using the province of Manitoba as a sample for the rest of Canada. Testing is one of the first important steps to keeping the spread of the virus down. We will compare rates of testing among FN/M/I people in Manitoba (looking at First Nations, Metis and Inuit groups separately) to rates of testing in the rest of Manitoba. This information can then be used to direct and scale-up the public health response to COVID-19 where it is most needed. Using administrative data on Manitobans' health from the Repository at the Manitoba Centre for Health Policy (MCHP), we will look at where testing is occurring geographically, what the testing rates are and whether FN/M/I people are being tested at a different rate than other Manitobans, and how many tests are likely going to be needed to keep the spread of COVID-19 under control. We will also develop methods to automate these queries in the data, so we can monitor the trends in real time throughout the pandemic. The findings will be shared with FN/M/I health leadership and with the Manitoba Government's Department of Health. With access to the latest data, these decision makers can then respond quickly to issues that arise.",2020,2020,University of Manitoba Community Health Sciences,238437.75,Human Populations,Other,Unspecified,Unspecified,Indigenous People | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C03067,172668,"Scalable, Customizable, Digital Health Communication Materials to Help Canada Address the COVID19 Pandemic","During the COVID-19 pandemic, people in Canada and elsewhere will be asked to follow public health guidance that will change over time and create challenges in people's lives. This guidance is based on science that is not always explained clearly. This project will create digital health materials like videos and web applications that will help people better understand the science about COVID-19, including things like the science behind why effective handwashing is so important, why local statistics about cases and deaths seem to fluctuate a lot, how different ways to limit transmission of the virus work, what treatments for COVID-19 are being studied and what those studies are finding, and what vaccines against COVID-19 are in development and how the vaccines are performing in clinical studies. Working with a team of highly-qualified scientists, doctors, nurses, and citizen partners, we will develop twelve different materials on different topics related to COVID-19. We will make sure the materials are accurate, understandable, easy to use, and that they can be used by people across Canada who may face barriers; for example, people who are deaf or hard of hearing, and people who have slower or more expensive internet connections. After we have developed them, we will test the materials to see if the materials make sense to people, help people understand the science, increase trust in science and public health, and encourage behaviour that will help Canada and Canadians deal with the COVID-19 pandemic. We will make the materials available in English, French, Mandarin, Cantonese, Punjabi, Spanish, Arabic, Tagalog, Persian (Farsi), and Urdu. All the materials will be available for free to anyone in Canada and anywhere in the world with an internet connection. We will release all the software code we develop under an open source license so that anyone who wants to do so can use it to build on our work, including updating the science as the science continues to change.",2020,2020,Université Laval Family Medicine and Emergency Medicine,233472,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C03068,172739,"Advancing healthcare for COVID-19 in Ontario: Strengthening providers' capacity for best practices in African, Caribbean and Black community service provision","The ongoing COVID-19 pandemic represents an unprecedented challenge for healthcare systems across the world. African, Caribbean and Black communities (ACB) include some of the most vulnerable populations in terms of their susceptibility to COVID-19 and their access and receipt of necessary and appropriate health care. The goal of this study is to improve the health system's response to COVID-19 by minimizing its spread and consequences in ACB communities. Specific objectives are to: 1) Engage ACB communities and health provider stakeholders in research and decision-making processes 2) Examine the contextual vulnerability and challenges experienced by ACB communities 3) Identify the adequacy and non-intended consequences of current health care practices on ACB communities 4) Increase individual, community and organizational capacity and leadership and generate strategies to address COVID-19 related-health outcomes, and 5) Share new knowledge and support its translation into policy and practice models to mitigate the impact of COVID-19 on ACB communities. The project will take place in four phases in two sites in Ontario (Toronto and Ottawa). A local advisory group will ensure consistent community engagement and capacity building. Our research team is comprised of influential and committed researchers, community leaders, healthcare providers and knowledge users from diverse backgrounds and disciplines across Ontario. The expected impacts of the proposed research that will be felt locally and globally by strengthening ACB community responses to COVID-19, identifying evidence-based interventions to strengthen the health system's capacity to care for ACB members, and generating knowledge to reduce COVID-19-related health inequities in ACB communities.",2020,2020,University of Ottawa Nursing,230270.25,Human Populations,Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Infection prevention and control | Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Research to inform ethical issues in Research | Community engagement | Indirect health impacts",2020 +C03069,172749,Venous Thrombosis Virtual Surveillance in COVID (VVIRTUOSO),"COVID-19 increases the risk of blood clots especially in patients who are admitted to hospital. Reports show a high rate of venous thrombosis (blood clots in the veins) affecting 3% of COVID-19 patients admitted to hospital and 11% to 70% of those who have life-threatening illness. This is higher than hospitalized patients with other medical illnesses. Venous thrombosis includes blood clots in the lungs (pulmonary embolism) and deep vein thrombosis (DVT). It is one of the most common preventable causes of death and disability associated with hospitalization. Most cases of venous thrombosis occur after hospital discharge and can be fatal if not diagnosed and treated promptly. The risk of venous thrombosis in patients with COVID-19 after discharge from hospital is not currently known. They are likely at high risk due to incomplete recovery, reduced mobility, older age and other medical problems. The overall goal of the VVIRTUOSO study determine the rate of venous thrombosis after hospital discharge in 500 patients with COVID-19 using a virtual monitoring program at 12 sites in Canada and the United States. We will also explore factors that increase the likelihood of venous thrombosis. As part of this study, we will also assess VTE awareness and patient-reported quality of the monitoring program (quality of communication and patient satisfaction). Our multidisciplinary team includes researchers, clinicians, patient partners and collaborators Thrombosis Canada (www.thrombosiscanada.ca) and the CanVECTOR Network (www.canvector.ca). We have the necessary experience, existing research network infrastructure, and knowledge translation mechanisms to successfully complete this study and disseminate the results rapidly and widely.",2020,2020,McMaster University Medicine,227743.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C03070,172748,Understanding and managing the effects of COVID-19 restricted visitation policies on the families and healthcare providers of critically ill patients,"There is worldwide spread of the coronavirus (COVID-19). Right now there is no vaccine or cure for the coronavirus. This means that most people can get sick with the coronavirus. Many hospitals around Canada developed visiting rules to prevent the spread of coronavirus and save masks, gowns, and gloves. Some visiting rules do not allow any family members to visit a patient in the hospital. When a patient is in the intensive care unit (ICU), they might be too sick to make decisions for themselves. This means that their family members might have to make important decisions for them. If a family member is not visiting the ICU, they may have to make these decisions over the phone. Making important decisions over the phone may be hard on the family member and the doctors or nurses. Visiting rules are important to prevent the spread of coronavirus and save masks, gowns, and gloves. We aim to understand what effect these visiting rules have on families, doctors, and nurses. We want to know what support they need while these visiting rules exist. First, we will see which Canadian hospitals have visiting rules to prevent the spread of coronavirus. We want to know how many hospitals do not allow family to visit a patient in the hospital during the coronavirus outbreak. Next, we will talk with patients, families, doctors, and nurses about how hard it is to not have families visit a patient during their hospital stay. We also want to know if these new visiting rules caused any mental health symptoms in family members. Last, we will ask families, doctors, nurses, and hospital leaders what they think would have helped make these visiting rules easier. It is important that we understand how hard these visiting rules are on patients, families, doctors, and nurses. Our goal is to work with hospitals to improve how they support families, doctors, and nurses when visiting rules are in place.",2020,2020,University of Calgary Critical Care Medicine,224076.75,Human Populations,Unspecified,Unspecified,Unspecified,Other,Nurses and Nursing Staff | Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C03071,172757,COVID-19 incidence rates among Canadian dentists as they return to work: a cohort study,"Since the COVID-19 pandemic emerged in Canada, in March 2020, dental regulatory authorities (DRAs) in provinces and territories across Canada obliged dentists to close their offices to routine care and provide emergency care only. The guidelines for dentists on the use of personal protective equipment or high-risk procedures (e.g., aerosol-generating procedures; AGPs), during the pandemic, vary between jurisdictions. Recently, some provinces have started allowing dentists to reopen their offices. However, guidelines on infection control, treatment and other procedures as dentists return to work have minimal evidence to support them. The overarching goal of this project is to estimate the incidence rate of COVID-19 among dentists and its risk associated with AGPs and N95 masks during the reopening phase of dental care services across jurisdictions in Canada. We are proposing a prospective cohort study of dentists during the reopening phase of dental services in Canada. An online questionnaire, adopted from WHO Unity Study protocols for assessment of COVID-19 risk among healthcare workers, will be used to collect information on socio-demographics, details of dental care provided to patients in the previous week, as well as symptoms related to COVID-19 and viral status (e.g., COVID-19 positive test). Saliva samples for detecting COVID-19 cases will also be collected at baseline and every four weeks. Participants will be followed on their viral status, clinical activities and COVID-19 status every two weeks post-baseline for a period of 12 months. Statistical analysis of the collected data will allow for the estimations of the incidence and prevalence of COVID-19 cases among Canadian dentists, and to identify the risk associated with AGPs and N95 masks. Our results will help the DRAs to monitor disease occurrence among dentists as they return to work and in developing evidence-based clinical practice guidelines and, as a result, prevent further spread of COVID-19.",2020,2020,McGill University,221955.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Dentists and dental staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics,2020 +C03072,172679,"Impact of the COVID-19 pandemic on Canadians living with mental illness, and their children","Deterioration of mental health may be the most serious consequence of the COVID-19 pandemic. Social isolation, reduced activity, lack of opportunities, unemployment and financial uncertainty are known triggers of depressive episodes and suicides. Those living with pre-existing mental illness, and their children, may be among the most vulnerable to the indirect consequences of the pandemic. The healthy development of children depends on the health of their parents and children of parents with serious forms of mental illness are at increased risk of adverse outcomes. Now, with closed schools and reduced access to external resources, the wellbeing of children may be linked to the mental health of their parents even more tightly than before. To find out what is harmful and helpful for individuals and families, we will examine the exposure, coping and impact of the COVID-19 pandemic in over 1000 adults and children from 300 families, including 200 families where one or both parents are living with mental illness. We will monitor the course of the parent mental illness, and track the development of mental health in their children. We will examine strategies that may protect against ill consequences, such as active ways of coping, regular sleep and uninterrupted receipt of health services. We will map functional outcomes such as the achievement of milestones in children and record both positive and adverse outcomes, including suicide attempts. We will use this new knowledge to inform public health strategies and mental health service provision and make them sensitive to the needs of families, including those where parents are living with mental illness.",2020,2020,Nova Scotia Health Authority (Halifax),210063.75,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Research Nova Scotia,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C03073,172738,Living network meta-analysis and Rapid Recommendations for the treatment of COVID-19,"Patients and clinician worldwide need trustworthy, rapidly updated guidelines to inform their treatment of patients with COVID-19. This project will produce such guidelines. Trustworthy guidelines need trustworthy evidence summaries. These summaries need to be up to date and need to differentiate will done studies producing valid results from poorly done studies that are likely to be misleading. Some of the studies of COVID-19 treatments will be trustworthy, and others will not. The evidence needs to be interpreted properly by considering all the relevant studies addressing each treatment, and their strengths and limitations. In addition, it will be important to revise evidence summaries frequently as new information is published. We will publish trustworthy summaries of the evidence that will be updated continually as new studies are published. We will search many databases to detect and include all relevant trials COVID-19. We will evaluate how well designed and conducted the studies were. We will also combine the results from all of the most trustworthy studies in a single analysis that will allow users to compare all options. These optimal evidence summaries will inform trustworthy practice guidelines. We will create trustworthy guidelines by constituting a panel that includes experts in COVID-19, experts in assessing evidence, front-line clinicians treating COVID-19, and patients who have lived experience of COVID-19. Panel members will be free of conflict of interest. These recommendations will be produced quickly and revised constantly as researchers publish new data. Finally, we will publish our summaries and recommendations in websites that will be freely available to all. The work will be conducted in collaboration with a leading medical journal, the British Medical Journal, and will be published there. The work will also be conducted in collaboration with the World Health Organization, that will use our guidelines directly or with minor changes.",2020,2020,"McMaster University Health Research Methods, Evidence, and Impact",207236.25,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",,2020 +C03074,172755,COVID-19 and COPD: Important knowledge gaps in subclinical pulmonary disease in the Canadian population,"The rapid outbreak of coronavirus disease 2019 (COVID-19) has resulted in a public health emergency of unprecedented international concern. To adequately guide clinical and public health responses to current and future outbreaks, the World Health Organization has established identifying groups of individuals at high risk of severe infection as an urgent research priority. Chronic Obstructive Pulmonary Disease (COPD) is a prevalent underlying co-morbidity and a leading risk factor for complications of COVID-19, but little is known on specific pulmonary risk factors for COVID-19 severity. We propose to mobilize an existing resource, the CanCOLD longitudinal cohort, to address this knowledge gap. CanCOLD is a population-based cohort of 1561 individuals aged > 40 years categorized as healthy, ""at-risk"" (ex- & current smokers) and COPD recruited in 9 of Canada's largest cities, where COVID-19 transmission is the greatest. We will leverage this established cohort to assess the prevalence of COVID-19 and its presentation (asymptomatic and symptomatic) in COPD, at-risk and healthy controls via serological antibody test. We will also exploit pre- and post-outbreak data and biosamples collected by CanCOLD to characterize prevalence and hazard of COVID-19 hospitalization (with/without ICU) and death according to four pre-morbid pulmonary risk factors: pre-existing pulmonary disease (COPD, asthma, chronic bronchitis), severity of airflow obstruction, lung structure abnormalities, and use of respiratory medication. We will identify and characterize the immunologic profile of CanCOLD participants and its relationship with COVID-19 susceptibility and severity. Finally, we will investigate the impacts of social isolation and confinement on mental health amongst Canadians with chronic airway disease. Ultimately, this study will provide an integrated perspective on COVID-19 susceptibility that can guide recommendations for clinical practice and public health strategies.",2020,2020,Research Institute of the McGill University Health Centre Medicine/Epidemiology and Biostatistics,206665.5,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts,2020 +C03075,"172646, 175502",BLT-Lung mice for the rapid evaluation of COVID-19 therapeutics [Added supplement: COVID-19 Variant Supplement],Controlled animal studies of candidate anti-COVID-19 therapies are required to rapidly identify the most promising drugs and safely advance them to trials in human subjects. The animal models that best predict what therapies will perform similarly in humans are those that closely replicate the human condition. Primates closely resemble humans but rapid high-throughput evaluation of drugs in this animal model is not feasible for economic and ethical reasons. We are producing a unique mouse model that contains human lung implants that support SARS-CoV-2 infection and a human immune system capable of responding to the infection. This animal model thus closely replicates COVID-19 disease seen in humans. These mice are in high demand to evaluate drugs that have already proven safe for the treatment of other diseases and drugs showing strong anti-SARS-CoV-2 effects in the laboratory. We will produce these mice and rapidly assess some of the most promising therapeutic candidates that have been identified as potential treatments of COVID-19. These studies will allow us to rapidly determine the impact of numerous promising compounds in a sophisticated animal model that closely resembles human COVID-19 disease in order to better predict their success in humans and speed their course towards clinical use.,2020,2022,"University of Saskatchewan Biochemistry, Microbiology & Immunology",239943.5,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C03076,172691,Dietary change during COVID-19: A population-based study in Atlantic Canada to build evidence for government economic and social policy responses,"Consumer food environments have been transformed during the COVID-19 pandemic. Early monitoring suggests people may be changing their consumer habits and dietary choices in unprecedented ways. Poor diet is already a leading cause of death and disability in Canada. Inadequate physical and economic access to food can have serious adverse effects on diet-related health and increase health care costs. Existing government monitoring in Canada will not be able to capture the dietary information we need to understand the breadth of dietary compromises being made, and the differential impact of COVID-19 for different populations, including important risk predictors such as age, sex and gender, income, employment, receipt of economic relief, and rural residence. To respond most rapidly and feasibly with a robust study design, we will focus on residents of the four Atlantic region provinces, who have among the highest burden of diet-related chronic diseases and obesity in Canada. This study is based in methodological approaches from nutritional epidemiology but draws substantially from our expertise in spatial and social epidemiology, and health economics. It leverages Canada Research Chair-and national agency funded teams, with links internationally. This population-based research will help us to better understand dietary risks and disparities resulting from COVID-19. The evidence we build will support governments across Canada to design economic and social policies and population interventions to mitigate the consequences of COVID-19.",2020,2020,Dalhousie University (Nova Scotia) Health Administration,200265,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C03077,"172727, 175521",Development of a Microwave Enabled Bio-Nano-Microfluidic Device for Point-of-Care Diagnosis of COVID-19 [Added supplement: COVID-19 Variant Supplement],"The COVID-19 crisis has caused over 280k deaths with more than 4 million infections as of May 8, 2020. These numbers are increasing and may peak again with reopening of businesses. This tragedy could be prevented from happening or its impact could be largely minimized if rapid, massive-scale testing can be performed at community level without the need of highly trained professionals and expensive equipment. This is also the highly recommended action among the immediate next steps by World Health Organization (WHO). The proposed project aims to develop such a system for rapid point-of-care (POC) diagnosis of the COVID-19 virus by leveraging the team's expertise in engineering, nanotechnology, viral immunology and clinical medicine. The proposed system is a palm-sized instrument that consists of a battery-powered microwave circuitry and a microwave-microfluidic device with its sensor surface modified by functionalized gold nanoparticles (gNPs) that specifically recognize the COVID-19 virus. The output is a yes/no answer via a light indicator. A test can be done within 30 minutes including the sample preparation, which is completed by simply stirring a nasopharyngeal swab containing a tested person's sample in a buffer solution. The system allows a test to be completed with a small drop of the sample solution (5 microliter) that is filled in the inlet reservoir and drawn to pass the detection chamber towards the outlet by capillary force. If the sample contains the COVID-19 virus, the virus will be captured by the functionalized gNPs coated on the sensor surface resulting in the change in the microwave spectrum. The microwave circuitry will analyze the spectrum and output a yes/no answer. It is expected that the availability of the proposed portable system will enable the test of COVID-19 at the community level such as at a drive-through point or in an ambulance, which will largely expand the testing capacity and thus assist in the control the COVID-19 pandemic.",2020,2022,University of Waterloo (Ontario) Mechanical Engineering,234472.29,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03078,172682,Uncovering longitudinal patterns of resilience and vulnerability in a pandemic: The All Our Families COVID-19 Impact Study Calgary,"The psychological and social effects of the COVID19 pandemic are pervasive and are impacting current mental health and relationships, with potential long-term effects, notably in youth. Youth is a developmental period of significant social, emotional, biological, and contextual change, simultaneously associated with a surge in mental health difficulties. Preliminary evidence at the national level is indicating reduced mental health during the pandemic, particularly among youth. High-quality, contemporary data on coping and recovery for families and youth during and after an unprecedented pandemic is crucial to inform further action and resource allocation in any future periods of lockdown, increased or re-infection, and future pandemics. Further, the acute and sustainable costs and benefits of aggressive public health measures such as physical distancing on the well-being of families and communities are unknown. The All Our Families (AOF) study, an ongoing prospective pregnancy cohort in Calgary, will survey families at three times points over one year to capture the discrete and longitudinal patterns of direct and indirect impacts of the pandemic on mental health, social connections, school achievement, sleep, and screen-time. AOF is uniquely positioned to disentangle emerging and sustained vulnerabilities from pre-existing vulnerabilities to development using longitudinal data that reflect the individual, family, and community determinants of health. Longitudinal data analysis will uncover patterns of resilience and vulnerability immediately, and over time for mothers and youth. Identification the factors that influence family and youth health and well-being during a pandemic is critical to the development of public health communications and strategies to improve outcomes.",2020,2020,University of Calgary Community Health Sciences,197561.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Alberta Innovates | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Social impacts",2020 +C03079,"172716, 175509, 175578",Point of Care Heart-Lung Imaging for Patients Presenting with COVID-19 Symptoms: Artificial Intelligence Precision Modeling for Prediction of Outcomes [Added supplement: COVID-19 Variant Supplement],"The global COVID-19 pandemic has placed a huge burden on health care systems and upended our way of life. It is caused by the highly infectious virus, SARS-CoV-2. Rapid and accurate testing for viral infection is needed to prevent spread of disease in hospitals and the community so that infected people can be identified early and treated effectively. EARLY COVID-19 symptoms are similar to many other respiratory viruses, like the flu and common cold, making it hard to identify in sick patients.The current approach to SARS-CoV-2 testing can be inaccurate and slow to return results. Improving diagnosis of COVID-19 will be even more important as flu season approaches. Our experience to date in treating patients with COVID-19 symptoms has shown that ultrasound imaging of the heart and lung may help identify positive cases earlier. Ultrasound is fast and safe. It can be performed at the bedside [point of care ultrasound (POCUS)] when patients first enter the hospital, by any physician with remote support from POCUS experts. In this study, we will test if adding heart and lung ultrasound images to existing clinical and laboratory tests can improve the accuracy and speed of COVID-19 diagnosis. A total of 16 hospitals across British Columbia and Ontario will participate in this study, and we will analyze this large data set using artificial intelligence (AI). Our team has already developed a platform to share ultrasound data and applied AI to study other heart diseases, so we are ready to rapidly apply this approach to COVID-19. If POCUS is effective it would allow earlier treatment and isolation of positive cases, reducing exposure of frontline health care workers and the public to the virus, improving both patient care and the distribution of health resources like personal protective equipment, intensive care beds and ventilators. Because POCUS-based COVID-19 diagnosis can be performed remotely it could also be applied in long term care facilities and in rural areas.",2020,2022,University of British Columbia Medicine,300728.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +C03080,172730,Deferred Care Outcomes in Canadian Children and Youth: Measuring and Mitigating Risk during COVID-19,"Early data from Canada and other countries around the world suggest that children are less likely to be directly affected by COVID-19 compared to adults. However, there are concerns that children may suffer important health implications related to efforts to control the spread of COVID-19, such as limited or suspended in-person physician appointments as well as parental concerns about contracting the virus in doctor's offices or Emergency Departments. The areas of highest concern are missed immunizations and important primary care visits such as those for newborns directly after birth, and delayed care for illnesses which result in children being critically ill. Currently, there are no data or studies that have investigated these unintended consequences of the pandemic in Canada. Using the well-established health data systems in Ontario and Manitoba, the goal of this project is to provide a robust and timely understanding of whether such responses to the pandemic have negatively impacted the health of children in these provinces. This assessment will include outcomes such as a reduction in routine vaccination and increases in serious illness and death. We will also examine whether specific subgroups of children, such as those with complex medical conditions and recently arrived refugee and immigrant children are at particularly increased risk of poor outcomes. We will prepare reports of these outcomes by local health regions and public health units and work with policymakers in both provinces to inform mitigation strategies. We will develop a core set of measures that we will report on over the course of the pandemic and its related restrictions. We will share data definitions and codes for conducting these analyses with national organizations such that other provinces may conduct similar analyses.",2020,2020,Hospital for Sick Children (Toronto),194014.5,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Internally Displaced and Migrants | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions | Policy research and interventions,2020 +C03081,172637,Liver as a bioreactor for robust production of SARS-CoV-2 neutralizing antibodies,"Passive immunization is when the serum of recovered patients is transferred to patients suffering from the disease. This serum contains the necessary antibodies produced by the recovered patient's immune system to fight-off the infection. However, this approach to treating infections requires large amounts of convalescent serum, which is difficult to obtain. A novel and promising strategy would be to artificially produce the selected antibodies that would fight-off the infection. However, antibody manufacturing at large scales is a fundamentally slow and laborious process lacking the infrastructure within Canada. Here, we use a more scalable, well understood, already established and approved platform technology, namely lipid nanoparticles, to deliver messenger RNA to the liver, where this antibody will be produced through the natural biochemical processes of the human body and secreted into the systemic circulation. The liver naturally produces over 90% of proteins in blood circulation and has the remarkable ability to produce antibodies also. We will modify the mRNA sequence that encodes the antibody so that it can access the lumen of the lungs where it is most needed to protect epithelial cells from being infected by the virus. The end result is a formulation that generates the antibody in the liver and will afford robust immune protection against virus in the blood and in the lungs. Our proposal requires funding to support the generation of the mRNA material, preparation of the nanoparticles using well-established and scalable procedures, and subsequently testing them in mice. This technology expands upon existing lipid nanoparticle technology that is currently being evaluate as a COVID-19 vaccine in phase II clinical trials (Moderna, CureVac, BioNTech).",2020,2020,University of British Columbia,178083.75,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2020 +C03082,172685,Weathering adversity: toward mitigating the impact of prolonged school closure and social isolation on mental health and lifestyle behaviours of elementary school children,"In early 2020, the COVID-19 pandemic engulfed the world, leading to drastic measures to limit the spread of the virus. These measures included closure of schools and orders to stay home for many weeks. Although these measures are necessary to prevent the virus from spreading, they also created a lot of hardship, particularly among school-aged children. This research builds on our 12 year partnership with a program called APPLE Schools (http://www.appleschools.ca/) which delivers a very successful intervention to promote healthy living and mental health to vulnerable kids from disadvantaged settings and currently operates in 74 elementary schools in northern Alberta, British Columbia, Manitoba and Northwest Territories. In 2018 we collected data on lifestyle behaviours and mental health in 16 schools from northern communities. Together with APPLE Schools, we propose research that collects information on children's mental health (mood, feelings, self-esteem), sleep, diet, physical activity, screen time and how these things may have changed after COVID-19 school closures. We will also ask questions about health-related school programming to find out what worked and what did not. This will help us understand what we can do to improve student supports offered by schools. As we are anticipating repeat school closures to contain COVID-19 and other outbreaks, the knowledge from this study has direct links to the re-opening efforts. The findings can be implemented immediately in schools across Canada and beyond.",2020,2020,University of Alberta,178028.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Social impacts,2020 +C03083,172666,Mitigating the long-term impact of the COVID-19 epidemic on cancer control and care,"The COVID-19 pandemic is causing major disruptions to several activities related to cancer control, prevention, and care. Cancer screening and prevention are now scaled back to prevent exposure of participants to the coronavirus. Many cancer diagnostic procedures and treatments have been delayed, modified, or suspended. As the containment measures are extended over several months, losses in the quality and quantity of cancer control and care will eventually lead to increases in incidence of cancers preventable via screening and vaccination, more advanced disease at diagnosis, and lower survival. The proposed research aims to study the long-term impact of the COVID-19 epidemic on cancer prevention, screening, and care to design evidence-driven mitigation strategies. First, we will assess the spectrum of cancer control and care activities that have been suppressed or altered because of the epidemic. Via a panel of oncologists from all subspecialties, public health experts, nurses, and pathologists we will identify processes of cancer control and care and estimate quantitatively the extent of influence on these processes by the epidemic and associated actions by the healthcare system. Second, we will conduct an in-depth literature review to obtain estimates of screening effectiveness and of the effects of delays in cancer diagnosis on clinical outcomes, such as stage at diagnosis and disease-free survival. Thirdly, based on the quantitative parameters obtained in the latter two research activities, we will develop models representing the population of Canada to estimate the impact of the pandemic on site-specific cancer trajectories. The models will be used to estimate the pandemic's impact in terms of cancer incidence (due to delays in diagnosis and suspended/deferred screening) and survival (due to delays in diagnosis and altered/suspended treatments) and based on these projections, we will propose strategies to reduce cancer morbidity and mortality.",2020,2020,McGill University Oncology,174356.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control | Health Systems Research,IPC in health care settings | Health service delivery,2020 +C03084,172632,"COVID-19 trilogy: ARDS, inflammation and coagulopathy.","The current SARS-CoV-2 epidemic has taken the world by surprise at the end of 2019. TH virus is highly transmittable and causes severe infections mostly in elderly and people with comorbidities such as diabetes, high blood pressure and cardia disease. The most evident medical complication initially reported and associate with the infection is acute respiratory disease syndrome (ARDS). Recent data clearly indicates that in addition to the lungs, other organs such as the heart and kidneys are affected by the infection. One common finding is the presence of blood clots in veins and arterioles of patients, pointing out to a deregulated coagulation process. In addition to study the inflammation during SARS-CoV-2 infection, our goal is to understand why such blot clots are formed. We will be using different mouse models to address how platelets may get activated and from undersized blood clots. Lastly, we will explore the potential benefits of administrating anti-platelet and anti-coagulant drugs to mice in oder to protect them from the disease.",2020,2020,CHU de Québec,169968.75,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +C03085,172721,Development of a Predictive Serologic Test for Cytopathogenic Autoantibodies in COVID-19 Patients,"Patients infected with the SARS-COV2 virus experience large variation in their clinical outcome. Most patients are asymptomatic or have mild symptoms while a smaller fraction of individuals develop devastating organ damage with fatal results. Currently, we have little insight into the factors that contribute to these dramatically different clinical outcomes. This proposal seeks to develop a test that will predict patients who may develop poor outcomes by measuring the emergence of antibodies that are destructive to tissues. These ""destructive"" antibodies are called autoantibodies. Normally our immune system generate antibodies protect us from viral and bacterial infections. We present preliminary data derived from a small cohort of COVID-19 patients that demonstrates the presence of autoantibodies in as many as 40% of infected patients. In some case these autoantibodies are present at high concentration. We will measure the presence of autoantibodies prospectively in a cohort of 150 patients that react against human lung cells, blood vessel cells and heart cells. The presence of these autoantibodies will then be correlated with the clinical course of Covid-19 infected patients. We will use well established mass spectroscopy methodologies to identify the proteins on human cells that are recognized by these autoantibodies. We will determine if purified autoantibodies from patients cause cell damage or death. Lastly, we will raise antibodies in mice directed against the proteins recognized by COVID-19 autoantibodies and determine if they cause injury to lung, heart, or blood vessels in animals. These efforts will allow us to develop a test to identify the emergence of autoantibodies in COVID-19 patients that will aid in stratification and the application of anti-viral therapeutics for those patients predicted to have unfavourable outcomes.",2020,2020,University Health Network (Toronto) Medical Biophysics,161606.25,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2020 +C03086,172630,Identification and validation of nutraceuticals that prevent SARS-CoV-2 infection,"COVID-19 is a significant global health burden and new strategies are needed to reduce the risk of SARS-CoV-2 infection. In this project, we will test nutraceuticals (i.e., bioactive molecules from food) to see if they bind to and inhibit the entry of the virus into the cell. Interestingly, using computer modeling, nutraceuticals have been predicted to bind to SARS-CoV-2. In aim 1, we will directly test if nutraceuticals bind to the virus and prevent its entry into the cell. In aim 2, we will determine the dosing strategy (i.e., how much and how often you need to take the supplement so that the nutraceutical can get to the lungs and bind to the virus) to provide maximal protection. In aim 3, we will test the nutraceuticals anti-viral effects in mouse models. Through this work, we will directly determine which nutraceutical can bind to and inhibit SARS-CoV-2 infection and provide a new approach to reducing the risk of infection.",2020,2020,University of Guelph,158437.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C03087,172670,"Rapidly assessing the impact of the COVID-19 pandemic and response on clinical and social outcomes, service utilization, and the unregulated drug supply experienced by people who use drugs in Toronto","People who inject drugs are at high risk of dying of overdose in Canada. This overdose epidemic claimed almost 15,000 lives between 2016 and 2019, and in response Canadian municipalities, including Toronto, developed a network of harm reduction, clinical and social services to try to prevent these deaths. However, starting in March 2020, the COVID-19 pandemic has created major barriers that prevent people who inject drugs (PWID) from accessing these services and avoiding illness and death. This includes the closures of supervised injection facilities, lack of access to clinicians to provide addiction treatment, and a lack of stable housing which makes it difficult to engage in physical distancing. Simultaneously, Toronto experienced a spike in overdoses in March and April, reversing a year-long trend of declining overdoses, which appears to be related to the COVID-19 pandemic and its restrictions. It is not known, however, exactly how PWID are being impacted and how services need to be changed to prevent them from succumbing to the ongoing epidemic of overdose and the COVID-19 pandemic. This project is using a unique research tool to explore that issue: the only cohort of PWID in Canada that has full linkages to individual clinical data. We are therefore able to rapidly assess people's clinical outcomes--including COVID-19 diagnosis, overdose, loss of access to addiction treatment, and the severity of other health conditions--to their self-reported behaviours. By doing so, we can understand the many ways that the COVID-19 pandemic is directly affecting this vulnerable group, and identify those at highest risk of both COVID-19 and overdose, and how these risks interact. To understand the population-level impact of the pandemic on PWID in Toronto, this study will also track how distancing restrictions are impacting the use of services to prevent overdose across the city, including addiction treatment access, supervised injection services, and street drug checking.",2020,2020,Unity Health Toronto,155070,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts,2020 +C03088,172667,The reorganization of institutional and community services for people experiencing homelessness and the needs of people experiencing homelessness to deal with the COVID-19 pandemic,"Considerant les mesures de confinement adoptees par le gouvernement, les restrictions en termes de rassemblement et de deplacement, les fermetures des espaces publics mais egalement les espaces prives a caractere public comme les commerces, les centres commerciaux, les bibliotheques, etc.. , la realite des personnes en situation d'itinerance (PSI) a profondement change dans les derniere semaines tout comme celles des pratiques d'intervention dans ce champ. Or, peu d'etude s'interessent a comprendre les impacts tant sur les organisations, les services, les intervenants que les personnes concernees tout comme les mecanismes et les strategies d'adaptation mis en place. L'objectif de cette etude est donc de comprendre cette resilience des organisations, des intervenants tant institutionnels que communautaires et des personnes en situation d'itinerance. En observant et comparant dans les differentes regions du Quebec, les adaptations, les transformations mises en place ainsi que les resistances rencontrees pour repondre a cette pandemie, le projet vise a documenter et faire circuler les reponses offertes en termes d'intervention dans le champ de l'itinerance, les impacts de la COVID sur les intervenants et leurs pratiques dans differents milieux d'intervention et sur les PSI dans leurs routines et leurs besoins en contrastant sur les dimensions du sexe, du genre, de l'orientation sexuelle, de l'age, du type d'itinerance vecu et des difficultes personnelles associees notamment sante mentale et consommation de drogues) Par la creation d'un Observatoire Itinerance-COVID19, cette etude vise a produire des analyses axees sur l'utilisation des resultats par les professionnels et les decideurs, et un transfert des connaissances oriente vers le partage des lecons apprises ici pour mieux soutenir ailleurs afin de soutenir et renforcer la resilience de tous dans le contexte de cette pandemie.",2020,2020,Université de Montréal Travail social,154695.75,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C03089,172673,COVID-19 Variant Supplement - Assessing the impact of the COVID-19 pandemic on social and health outcomes among young people: A mixed-method comparative analysis in Canada and France [Added supplement: COVID-19 Variant Supplement],"Youth (<30 years) are among the most at risk for longer-term social and health consequences due to COVID-19-related public health measures (e.g., physical distancing) and the associated social and economic impacts, including unemployment, as well as isolation from their social networks and disruption to their education during key periods of the early life course. To advance evidence and to inform adaptive social, economic and public health responses among youth, we are prepared to rapidly launch a one-year multi-site mixed-methods study. Our aim is to generate new context-sensitive and population-specific data to document how policy and program responses can be optimized to improve the lives of youth in two key international settings: Canada and France. While both Canada and France share some commonalities (e.g., high-income countries, publicly funded health care systems), there are many important contextual differences (e.g., severity and evolution of national and regional COVID-19 curves, economic support/employment insurance programs, community-based responses) that will benefit from empirical investigation as they relate to youth population health. We will conduct a multi-site concurrent mixed-methods study that includes: (i) a series of longitudinal qualitative research activities including semi-structured interviews with youth from across different jurisdictions in Canada (n=30) and France (n=30); (ii) interviews with key stakeholders (n=10 in each setting); and (iii) two national online cross-sectional surveys in both Canada and France with youth (at 6-month intervals). Throughout the duration of the proposed study we will engage in integrated knowledge translation and exchange (KTE) activities to systematically engage in rapid-cycle evaluation and advance actionable findings, including findings that are of relevance to national, federal and local policies and programs that can have an impact on youth social and health outcomes.",2020,2022,University of British Columbia Medicine,177179.1,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C03090,172750,Longitudinal impact of COVID-19 on clinical practice and well-being of global mental health professionals,"Due to the COVID-19 pandemic, health care workers face highly stressful and rapidly changing work environments, often caring for those with COVID-19 without adequate protective equipment while coping with their own fears of getting sick or infecting others. Studies from other pandemics tell us that health care workers often experience impairing psychological symptoms such anxiety, sadness, insomnia and general distress, which can be long lasting and lead to reduced quality of care and safety or to leaving their jobs. Mental health concerns in the population have increased because of the pandemic (e.g., isolation, anxiety, substance use), but accessing services is more difficult. Psychiatrists and other mental health professionals face increased demands and substantial stress; it is critical to understand their experiences to ensure the availability of high-quality services, including those using telehealth technologies like videoconferencing. This study uses detailed online surveys in 6 languages to assess the impact of the COVID-19 pandemic on clinical practice and well-being of global mental health professionals. The survey will be implemented at three time points to look at changes over time. Participants will be members of the World Health Organization's Global Clinical Practice Network, including 15500 mental health clinicians from 159 countries. The study assesses: 1) Effects of COVID-19 on work circumstances and services; 2) Work-related stress and distress; 3) Use of telehealth services and related concerns; and 4) Expectations, resource needs, and recommendations. The study responds to the CIHR call by providing evidence to inform clinical and health system management and public health response. Findings will inform CIHI (co-applicant knowledge user), the Government of Canada, WHO, professional associations and health systems as they work to ensure continuity of care for people with mental illness and to protect and retain the mental healthcare workforce.",2020,2020,University of Ottawa,137725.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03091,172680,Surveilling the impact of local public health on COVID- 19: A model and application for capturing high-resolution insights from the front-lines during a pandemic,"Local public health units, which are often buried within large health care authorities or municipal governments, have proved to be indispensable during the COVID-19 pandemic. In cities and towns throughout Canada, local public health units are responsible for implementing provincial and federal COVID-19 recommendations. These activities by local public units have led to unprecedented consequences for the operations of public health units themselves, and for the community. Unfortunately, there is currently no way to measure the activities of public health units and their impacts. This is unfortunate because such information would be very useful for researchers and decision-makers to learn from. We propose to undertake ""public health policy surveillance"" to capture local public health activities themselves and their consequences on CoVID-19 outcomes. First, we will use surveys and interviews to gather information from front-line public health experts. We will access those experts through our front-line public health network research partners, whose public units serve over two-thirds of the Canadian population. Through our surveys and interviews, we will 1) have baseline data on local public health activities, 2) learn how to collect this information regularly to understand local public health operations and outcomes, and 3) improve pandemic responses in the future.",2020,2020,University of Saskatchewan Community Health and Epidemiology,135458.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Saskatchewan Health Research Foundation,Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery | Health leadership and governance,2020 +C03092,172773,Development of a yeast-based immunoassay for SARS-CoV-2 serologic testing amenable to inexpensive local production,"To monitor the spread of the COVID-19 pandemic and test individuals for potential immunity, we need antibody detection tests, where a blood sample is checked for the presence of antibodies induced by past exposure to the virus. These tests are often expensive, requiring either a fully-equipped laboratory with highly trained technical staff, or costing many dollars per test for field-deployable ""strip tests"". Sending tests to a lab or paying a few dollars per test does not perhaps seem like a problem, here in Canada, but in our partner nation of the Philippines, both of these present significant barriers: public health dollars are sharply limited, and remote areas have very limited access to lab facilities and technical staff. Our goal is to create an antibody detection test that can be ""grown"" locally, here in Canada and in the Philippines. By modifying baker's yeast (S. cerevisiae), we can put antibody-binding proteins (antigens) on their surfaces, able to capture disease-induced antibodies found in blood samples. We test for the presence of these antibodies with an agglutination test: when the yeast cells settle to the bottom of a round well, in the absence of antibodies they form into a tight button that looks like a dot to the naked eye; or in the presence of antibodies they form larger clumps that stay more spread out and look like a flat sheet to the naked eye. A minimally-trained user can thus obtain a positive or negative result with no expensive instruments. The yeast (once designed) can be grown in a simple sugar solution, at a raw material cost that we estimate to be something less than 0.01 cents per test. We have demonstrated lab-bench success at detecting Chagas' disease and dengue fever antibodies, and now we propose to adapt the technique to detect COVID-19 antibodies and develop it in a fully deployable kit for use in under-resourced areas. Our first target is the Philippines, with the help of our collaborators at UP Manila.",2020,2020,University of Toronto Mississauga (ON) Chemical and Physical Sciences,134355,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03093,"172636, 175497","Contribution of genetic variation of ACE2, the receptor for SARS-CoV-2, to COVID-19 disease expression and development of therapeutics [Added supplement: COVID-19 Variant Supplement]","The coronavirus causing the COVID-19 pandemic infects by binding to a receptor called ACE2 on the surface of cells lining the lung. One reason for the virulence of this new virus is the strength of its binding to ACE2. However, one of the leading mysteries of the outbreak has been the wide range of responses to infection, from a complete absence of disease in some, to life-threatening pneumonia in others. Regional difference across the world in disease expression have also been reported, as has a striking increased severity of COVID-19 in men compared to women. Here, we propose to investigate whether genetic variation in the human ACE2 receptor protein underlies these differences. We will test this by making all possible mutations in the ACE2 gene and testing impact on binding to the viral protein. Results from our study will have important impact on new development of therapeutics by improving computational models of ACE2-virus interactions used to design drugs blocking this binding. Another important outcome from our study would be the identification of genetic variants of ACE2 with heightened binding affinity for the viral protein. Such variants can be used as novel therapeutics by out competing virus in a patient's system, preventing virus from infecting host cells. Critically, once established, our platform will be highly versatile and readily allow testing new strains of the COVID-19 virus for increased or decreased infectivity. This platform will also be invaluable to provide a more rapid response to any new virus that appears in the future that infects cells by binding the ACE2 receptor.",2020,2022,University of British Columbia Cellular and Physiological Sciences,168810.5,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies",2020 +C03094,"172633, 175523",Peptide macrocycle decoys against COVID-19 viral spike protein [Added supplement: COVID-19 Variant Supplement],"Peptides are potent, easy-to-synthesize, and synthetically accessible molecules that can specifically interact with pathogens. Peptides have been used to treat diabetes, neuropathic pain, cancer, and HIV. As chemists we have very recently invented news ways to make peptides both more potent as well as fluorescent in order to see where they go and how they act. We are poised to interface our technology with molecular modelling to synthesize peptides that will intercept the virus before it can enter a cell. These peptides can be injected or nasally delivered for therapy and can be used prior to vaccine development or in cases where certain patients cannot be vaccinated.",2020,2022,University of British Columbia Chemistry,162453.22,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C03095,"172687, 175546","Gig couriers delivering people, food and packages in a pandemic: Containment strategies to mitigate the occupational and public health impact [Added supplement: COVID-19 Variant Supplement]","Gig courier workers, such as Uber Eats, Amazon Flex, and Lyft drivers, have been busier than ever during the Canadian COVID-19 pandemic as the public attempts to avoid illness by ordering take-away food, shopping online and taking ride-hails rather than public transportation. This places gig courier workers in a unique position to become infected with COVID-19 and transmit it to others as they move people, food and packages from one location to another. Although gig couriers are key vectors between where people live (e.g. homes, care facilities) and the outside world, formal strategies do not exist to protect them from exposure and to mitigate their role in disease transmission. Importantly, this risk is not expected to change anytime soon as the high use of couriers will likely not decline as the economy re-opens. This study will contribute to coronavirus containment strategies by identifying disease transmission risks embedded in gig work contexts and practices, developing clear and tailored interventions for gig courier workers about gig courier disease-related safety and transmission, and widely disseminating results, in live time, as they are identified. Using framework analysis explicitly geared towards generating policy- and practice-orientated findings within limited time periods, we will: document existing courier safety organisational policy; map gig courier worker work, disease exposure and transmission conditions (with attention to gendered dimensions) via social media forums and in-depth interviews with workers and courier firm representatives; and categorise disease transmission risks. Supported by our Strategic Advisory Committee of unions, government municipalities, employers, and vulnerable worker advocates, and using real-time public health communications, this study will create effective national interventions to reduce gig courier disease exposure and protect the public health of Canadians using these courier services.",2020,2022,University of Waterloo (Ontario) School of Public Health and Health Systems,159195.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C03096,172745,Partially Nested Randomized Controlled Trial to Evaluate the Effectiveness of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Program to Reduce Anxiety among Vulnerable Persons with a Pre-existing Medical Condition,"People with the autoimmune disease scleroderma are vulnerable in COVID-19 due to frailty, lung involvement, and immunosuppression; they are representative of vulnerable groups in terms of COVID-19 mental health ramifications. No previous randomized controlled trials have tested mental health interventions during infectious disease outbreaks. We leveraged our existing ongoing cohort of over 2,000 people with scleroderma and existing partnerships to launch a new cohort, the Scleroderma Patient-centered Intervention Network (SPIN)-COVID-19 Cohort. We enrolled over 800 people in the cohort to assess mental health during COVID-19. The SPIN-CHAT trial is embedded in the cohort and will test a 4-week (3x/week) videoconference intervention that provides social support and positive mental health education. The primary outcome is anxiety symptoms. Secondary outcomes include symptoms of depression, fear, loneliness, boredom, and social interaction. Our team is uniquely positioned to successfully carry out this research with high-level expertise, an experienced patient advisory team, support of >25 patient organizations internationally, and existing infrastructure. We have successfully enrolled and randomized 172 participants into intervention (N = 86) and waitlist groups (N = 86), and we are delivering the trial intervention. As of May 11, 2020, the SPIN-CHAT Trial is only major COVID-19 mental health trial geared at vulnerable populations in the community. SPIN-CHAT is being tested among people with scleroderma, but could be used with any population of vulnerable individuals who are isolated and experiencing high levels of anxiety in COVID-19, such as people with pre-existing medical conditions or older persons. The study received funding of $100,000 to set up the cohort and deliver the intervention plus $65,000 from Scleroderma Canada, but lacks funding for statistical analyses, follow-up after the immediate end of the intervention period, and knowledge dissemination.",2020,2020,Lady Davis Institute for Medical Research (Mtl) Psychiatry,117264.75,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03097,172737,Can COVID-19 and maternal antibodies to SARS-CoV-2 be transmitted through human milk? Implications for breastfeeding and human milk banking,"Protecting the health of newborns is of utmost importance, particularly true at the time of a pandemic such as COVID-19. Human milk, the optimal infant nutrition, modulates the developing human virome and provides protection against infectious diseases especially those of the respiratory and gastrointestinal tracts. There is emerging evidence that SARS-CoV-2, the virus responsible for COVID-19, may be found in human milk which has resulted in conflicting advice from professional groups recommending caution for breastfeeding while a mother is COVID-19 positive. Even less is known about SARS-CoV-2 specific antibodies that may be present in human milk, potentially offering immunoprotection to infants. For vulnerable infants, human donor milk provides an important bridge to mother's milk during hospitalization that helps to protect against neonatal morbidities. This donor milk is provided globally by more than 450 milk banks. Past global epidemics, such as HIV/AIDS, have had devastating effects on breastfeeding and milk banking as a result of social, policy and public health responses to perceived risks. There is a critical, time-sensitive need to develop evidence-based guidance on breastfeeding and human milk banking during the COVID-19 pandemic. This project aims to quickly and efficiently determine the SARS-CoV-2 transmissibility in human milk and measure the associated antibodies along with the impact of thermal pasteurization on SARS-CoV-2 infectivity. Our newly assembled team of experts in breastfeeding, human milk banking, infectious disease and molecular virology will immediately redirect parts of their established research programs including established infrastructure and personnel to accelerate the availability of critical time-sensitive evidence to guide public health recommendations about breastfeeding, handling of raw breastmilk by mothers and front-line workers in hospitals and in donor human milk banks.",2020,2020,Sinai Health System (Toronto),115683.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03098,172663,Psychological First Aid Training to Address COVID-19 Related Stressors,"Emerging evidence tells us that the COVID-19 pandemic will have far-reaching impacts on the emotional and psychological well-being of adults and children. Recent reports also indicate that COVID-19 is likely to result in an economic recession and that the psychological and emotional effects of the pandemic for vulnerable populations - namely children and their families - will endure well beyond the virus' physical impacts. Despite the fact that there is evidence that Psychological First Aid (PFA) could minimize the emotional and psychological toll related to COVID-19, PFA training has not been a focus of the pandemic response in Canada. According to the World Health Organization, PFA is a brief-intervention that provides targeted and practical psychological support to help individuals manage distress related to large crises, such as a pandemic. PFA is widely endorsed by global public health authorities, including the WHO and the United Nations, and has been used to provide widespread psychological and emotional support to the public during extreme events (e.g., Hurricane Katrina) and other viral pandemics (e.g., the Ebola Outbreak). We have chosen to implement and evaluate a PFA training program for mental health counselors - called LIVES for Families - to see if it supports them to address COVID-19 emotional and psychological stressors experienced by caregivers and their children. Reducing the potential burden of child and family suffering attributed to COVID-19 remains a crucial public health challenge. Our work will provide information about: (a) the acceptability and feasibility of implementing the LIVES for Families PFA Training Program with mental health counselors to address COVID-19-related stressors among caregivers and their children; and (b) generate the initial research necessary to develop an evidence-based, COVID-19 PFA training program for widespread implementation and evaluation in the Canadian context.",2020,2020,McMaster University Psychiatry & Behavioural Neurosciences,107403,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03099,172770,Expression and Purification of COVID19 Virus Spike (S) Protein for Diagnostics and Vaccines [Added supplement: COVID-19 Variant Supplement],"Projects described within this rapid response proposal relate to diagnostics and vaccine production. The reagents generated also have longer term ramifications for studying virus attachment and developing inhibitors that block host cell entry and virus mediated fusion. The work in this proposal focuses on the spike protein (S) of the coronavirus which mediates attachment and entry into the host cell and is the major target of neutralizing antibodies that block infections. The first goal of this proposal is to generate large quantities of the S protein is a mammalian expression system that can be easily scaled up for large scale production. The protein generated in this procedure can be used to produce immune diagnostic kits as well as serve as a component of subunit vaccines or booster shots directed against COVID-19. The second aim describes the generation of recombinant vesicular stomatitis (VSV) viruses that express the Spike (S) protein derived from COVID-19 virus. In the first experiments, VSV genome vector is modified to contain coronavirus S protein in place of its G glycoprotein which normally mediates attachment and entry of the host cell. The S protein changes the tropism of the recombinant virus and provides a new antigen target for the immune system. VSV is highly attenuated in human cells and is tightly controlled by the host antiviral interferon system. It is also the vaccine vector for the highly effective Ebola virus vaccine. The diagnostic and vaccine reagents developed in this proposal will be distributed and tested by colleagues at the Canadian Center of Vaccinology (Halifax) and VIDO-InterVac Vaccine Cenre in Saskatoon. The final aim of this proposal will use the reagents generated in the proposal to study cell receptors for COVID19 coronavirus and study infections in susceptible cells using model viruses of lower risk and pathogenicity.",2020,2022,Dalhousie University (Nova Scotia) Microbiology and Immunology,143072.75,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C03100,172863,Assessing the Association Between Frailty and Outcome of COVID-19 Infection,"From https://www.cfn-nce.ca/project/assessing-the-association-between-frailty-and-outcome-of-covid-19-infection/ : A novel coronavirus, SARS-CoV-2, emerged in December 2019 in Wuhan, China. This new virus causes a respiratory illness known as COVID-19, and is now the cause of a severe pandemic. Rapid transmission of this virus is fuelled by a high reproductive number, the substantial number of mild illnesses, and transmission which occurs prior to onset of symptoms or from patients with mild disease. Although many cases of COVID-19 are mild, nearly one-fifth of infected patients experience severe or critical illness; the infection appears to have an overall case fatality rate of 2-3% and up to 7% of patients require intensive care unit admission. Strikingly, very few children develop illness. Adults across all age-categories may develop severe illness, but older adults are clearly disproportionately affected. In the largest case series to date from China case fatality rising drastically from 0.2% for individuals < 40 years of age to 14.8% for those ≥ 80. Since that publication, it has become evident that the frail elderly appear to be even more affected than others: almost half of Canadian deaths to date have occurred in residents of long term care homes, and the case fatality rate in residents the first described outbreak in a long term care home was 30% (this is actually an underestimate because the manuscript was written and published while the outbreak was on-going). Because many patients survive hospitalization without specific antiviral therapy, considerable effort has been expended to identify risk factors for severe outcomes because these would permit decisions about who should receive specific therapy once a therapy is identified, and because stratification by such variables would improve the implementation and interpretation of clinical trial data. To date, however, factors identified have not been highly predictive (e.g. male gender, smoking) or relatively uncommon (e.g. morbid obesity). None of the studies to date, however, have considered whether frailty might be an important predictor of outcome. Frailty is defined as a medical condition of reduced function and health in older individuals. In many sub-populations, it is more strongly predictive of health outcomes than age. Frailty may also be associated with significant declines in immunity, which may impair the ability to respond to COVID-19. Frailty is thus an important candidate measure to consider studies of COVID19. We propose an analysis leveraging an already created prospective cohort of COVID-19 infections, with the overall goal of identifying the extent to which frailty predicts outcomes of COVID-19 infections, and whether it should be considered - and is feasible to consider - as an inclusion criterion or a stratification variable in trials of therapeutics for this new infection.",2020,2020,Sinai Health System (Toronto),99483,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03101,172704,"Canada's COVID-19 Pandemic Response and Impact in Homeless or At-Risk for Homelessness, and Visible Minority Populations in Canada: A Mixed-Method Study","Vulnerable populations are more likely to live with chronic conditions, experience housing and food insecurity,¿precarious employment, and mental health challenges, which are exacerbated during times of crisis. Canadian pandemic responses to COVID-19 fail to identify the interaction of marginalization and health disparities that are intertwined with the social determinants of health, which if incorporated in emergency planning by public health officials can lead to equitable public health risk messaging strategies for vulnerable populations. Using a mixed-method design, the objective of the study is to build upon a pilot trial and measure the bio-psychosocial and economic impacts of the COVID-19 response on homeless, at risk of homelessness, and visible minority populations in Ottawa, Canada. Through mobilizing existing community partnerships, a survey will be shared on social media platforms and through relevant social service networks by individuals with lived experience of homelessness and poverty (community peers). The survey will collect data on the physical health, mental health, socioeconomic characteristics, and health and digital literacy skills of vulnerable populations during the COVID-19 pandemic. A sub-sample will complete telephone-based semi-structured interviews¿that¿will explore in-depth the experiences of vulnerable populations with¿physical distancing, exposure to public health messaging, and COVID-19¿related¿misinformation during the pandemic lockdown. The mixed-method analysis will examine patterns and relationships between the aforementioned factors of interest to inform digital and health literacy gaps, producing equitable pandemic policies in the future. By understanding the susceptibility of vulnerable populations and the unique communication outbreak disease management needs of said populations, the impact will have positive implications around the globe.",2020,2020,Ottawa Hospital Research Institute Internal Medicine,96962.25,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical | Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C03102,172681,Decision-making in the time of COVID-19,"The COVID-19 pandemic has led to an unprecedented global disruption, costing jobs and lives. Its effects can be halted or minimized if we adopt proper, flexible protective measures until a vaccine or treatment is available. But how do we increase the use of protective measures, such as hand washing and physical distancing, and promote the adoption of new measures, such as mask wearing and rotating schedules, as the economy reopens? People have a strong tendency to make choices that lead to immediate and certain rewards, while avoiding losses and placing less value on rewards that require waiting or that are uncertain, even when rewards are larger. These biases in our decision-making affect how likely we are to change our immediate behaviours in order to protect ourselves and other people. For over a decade, our team has studied this form of decision-making in Canada and parts of the world that were devastated early on by the pandemic (Italy), or that differed in their approaches to containing it (USA, New Zealand). We have succeeded in identifying effective ways to change these tendencies that can easily and rapidly be carried out, with high potential to make a real and sustained impact on the global fight against COVID-19. The aims of the proposed research are to 1. characterize and track biases in decision-making around people's willingness to use protective measures, and 2. optimize a scientifically based intervention that can help people overcome biased decision-making by training them to imagine personal scenarios. We also will determine the effects of workplace learning of COVID-19 health and safety measures on changes in decision-making and behaviour through our access to a pool of over 2.8 million frontline workers receiving such training. With the Public Health Agency of Canada as our Knowledge User, we can translate our findings into guidelines on when and how to safely lift restrictions on everyday activities while still under the threat of COVID-19.",2020,2020,"York University (Toronto, Ontario) Psychology",90056.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Research to inform ethical issues,Research to inform ethical issues in Clinical and Health System Decision-Making,2020 +C03103,172659,Implementation of public health measures for vulnerable populations during the COVID-19 pandemic in French-speaking African countries in conflict: Case study in Mali and Burkina Faso,"Le premier cas de COVID-19 en Afrique a ete confirme le 14 fevrier 2020 et, en quelques semaines, le virus s'est propage a tous les pays. L'impact de la pandemie de COVID-19 pourrait etre devastateur dans les pays africains, surtout ceux fragilises par des conflits, qui comptent des milliers de refugies, de personnes deplacees internes (PDI) et de migrants. En l'absence de traitements ou de vaccins, les gouvernements et les acteurs humanitaires ont implante des mesures de sante publique pour ralentir la propagation du virus. Au Mali et au Burkina Faso, ces mesures incluent l'isolement des patients COVID-19 et la mise en quarantaine a domicile des cas suspects. Des mesures de distanciation sociale et de confinement sont aussi implantees afin d'attenuer la pandemie. Pour les PDI et les migrants, la mise en œuvre de ces mesures est plus difficile en raison des conditions de promiscuite et de manque d'hygiene dans lesquelles elles vivent. De plus, plusieurs personnes ne sont pas au courant de l'existence de ces directives, ne les comprennent pas ou ne sont pas convaincues de leur importance. Cette recherche permettra de mieux comprendre les defis auxquels sont confrontees les autorites et les acteurs humanitaires dans la mise en œuvre des mesures de sante publique en riposte a la COVID-19, de meme que les difficultes que rencontrent les PDI et migrants pour adopter ces mesures. Elle etudiera la pertinence de chaque mesure par rapport au contexte specifique dans lequel vivent les PDI et les migrants et proposera des ajustements appropries. Nos resultats permettront d'identifier les meilleures pratiques et d'offrir une assistance adaptee aux besoins des PDI et des migrants afin qu'ils puissent mieux appliquer les mesures de distanciation sociale et de confinement. Nos resultats pourront contribuer a accroitre l'adaptation des mesures de sante publique dans d'autres contextes, afin de ralentir les epidemies en general.",2020,2020,Université Laval,83613,Human Populations,Black,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Burkina Faso | Mali,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C03104,172672,An increased risk of family violence during COVID-19 quarantine in Canada: strengthening social media-based collaborations between non-profit agencies to save lives,"Family violence (DV) increases in the wake of COVID-19. Those are experiencing while social distancing at home is significantly impacted due to the extraordinary stress families face. The Artificial Intelligence Lab for Social Justice lab at the University of Toronto has been collecting Tweets that contain terms related to COVID-19 (e.g., #2019nCoV, #COVID19) since January 2020. To present, our lab has collected approximately 90 million Tweets related to COVID-19. Our computational social science team uses machine learning approaches to examine 1.the impacts and service needs of COVID-19 on family violence survivors; 2.how provincial and city level non-profit agencies use Twitter to communicate with family violence survivors in the COVID-19 context; and 3.how the COVID-19 supportive information for family violence victims is diffused on Twitter. The project findings will provide rapid, real-time knowledge of family violence during the outbreak, and mobilize Twitter to support and ensure victims' safety.",2020,2020,University of Toronto,75517.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Social impacts | Communication,2020 +C03105,unknown,Utility of a Preclinical Model to Study the Impact of Vaping Products on Cardiopulmonary Outcomes,,2020,2021,Lady Davis Institute for Medical Research (Mtl),75000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03106,172657,Social frailty interventions that can best support vulnerable older adults during the COVID-19 pandemic: A rapid review,"By the year 2050, two billion people worldwide will be 60 years of age and older. Global life expectancies are also on the rise, leading to an increased number of seniors who will develop chronic conditions and frailty. Given these projections, frailty is fast becoming a public health concern. Frailty is multidimensional (it affects biological, psychological, and social processes of a person's life), and therefore can lead to reduced functional ability, falls, disability, decreased quality of life, and death. Of the three types of frailty (physical, psychological, and social), social frailty is the least well understood. It is defined as ""a continuum of being at risk of losing, or having lost, social and general resources, activities or abilities that are important for fulfilling one or more basic social needs during the life span"". During public health emergencies such as COVID-19, social vulnerabilities such as social frailty represent an even greater threat to the health of older adults. However, we know very little about the risk factors and interventions that may prevent or reverse social frailty. Therefore, our research goals are to better understand interventions addressing social frailty in older adults by conducting a systematic review and a realist review. The results of this work will help decision makers understand which social frailty interventions can best address the needs of vulnerable older adults impacted by isolation during COVID-19 or other disease outbreaks requiring similar public health measures.",2020,2020,North York General Hospital,75000,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C03108,"172735, 175524",Inferring undiagnosed sources of COVID-19 infections using viral genomes,"The ongoing COVID-19 pandemic is believed to be significantly influenced by asymptomatic SARS-CoV-2 patients. Understanding the role that asymptomatic patients play in the spread of the disease is vital for informing testing procedures. This project aims to build a tool to identify asymptomatic or undiagnosed patients by examining infected people around them without the need to directly test them, allowing health authorities to make rapid and better informed decisions. Viral genomes accumulate small changes, mutations, which usually are neutral in terms of disease progression. These can be used to trace transmission networks - individuals within the network will have acquired the disease from a single source and so will share the same variants. Current approaches do not detect utilize all variants especially the low-frequency ones and so rate less robust in building accurate transmission networks, and inferring transmission by asymptomatic carriers. By utilizing our previously developed tools and expertise in inferring HIV transmission networks, we will develop new mathematical models that are able to infer SARS-CoV-2 transmission. The sequencing data needed to map viral transmission will be acquired through a project funded by the Alberta Children's Hospital Research Institute (ACHRI) and Genome Alberta, which aims to sequence 1,900 COVID-19 patients. In collaboration with our partner organization, Public Health Laboratory under Alberta Health Services (ProvLab) who performs COVID-19 diagnostics for the province of Alberta, we will obtain information on asymptomatic patients who have tested positive for the virus, remove them from our data, and then see if we can retrospectively identify them as likely contacts between the symptomatic individuals.. The resulting tools can be extended for use across Canada, and potentially even model future outbreaks of infections diseases in humans, livestock, and wildlife.",2020,2022,University of Calgary Biochemistry and Molecular Biology,112364,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2020 +C03109,172703,Equity in Emergency Department Utilization in Alberta for Priority Populations during the COVID-19 Pandemic: Exploring Impacts of Changes to Healthcare and Healthcare Utilization through Administrative Data Analysis and Nominal Group Techniques,"Alberta has seen a marked decrease in emergency department presentations while pandemic control measures have been in place. In addition to public health measures including physical distancing, many patients who perceive hospitals as high-risk environments and may avoid emergency department visits, even when seriously ill. This can lead to health issues becoming worse and harder to manage. Harms associated with decreased emergency department use may be greater for some populations, who rely more heavily on emergency departments for their care. Frequent users of emergency departments are more likely to be low income and to be older. In Alberta and British Columbia, First Nations individuals utilize emergency departments at a much higher rate than non-First Nations individuals. This study builds on an existing emergency medicine research partnership with the Alberta First Nations Information Governance Centre, as well as connections to operational (Alberta Health Services) and research leaders in the areas of emergency medicine, seniors care and population health. Through information collected by the Alberta health system, we will compare emergency department use during the initial months of the pandemic to information collected last year. Among other outcomes, we will consider how numbers of ED visits, hospital admissions, deaths in ED and other serious conditions have changed during the pandemic. We will then determine if changes have been greater for First Nations, socially and materially deprived, remote and older populations than for the general population. Through structured engagement with patients, clinicians and health systems leaders, we will share findings and develop understandings of results. Highlighting harms and inequities arising from pandemic-driven changes in care patterns and systems will allow policy- and decision-makers to reduce the negative consequences of efforts to manage COVID-19.",2020,2020,University of Alberta Emergency Medicine,70377.75,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Indigenous People | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions",2020 +C03110,172734,Presence of viable SARS-CoV-2 virus in surgical smoke produced during electrocautery,"Electrocautery is an important, and in many cases, essential tool used during surgery. It is well established that electrocautery can produce aerosol, and previous studies have demonstrated that some viruses can be carried in the vapours from cautery. During the COVID-19 pandemic, out of an abundance of caution, protocols have been put in place to minimize potential exposure to this smoke that significantly reduce the capacity in our healthcare system to do surgery. High level personal protective equipment is required for these procedures when they do occur, and much of that equipment is currently in short supply. This study will be done in a biohazard level 3 laboratory and will examine if the virus that causes COVID-19 (SARS-CoV-2) is viable and present in the smoke produced by using cautery. This study will collect the smoke from using two different types of cautery on blood from a patient with COVID-19, from blood inoculated with SARS-CoV-2 and from cauterizing a culture plate with SARS-CoV-2. The vapour will then be cultured to see if SARS-CoV-2 can be grown, thus demonstrating if viable virus is aerosolized during cautery. Another test (RT-PCR) will be used to look for RNA from the virus to see if any is present in the smoke. A positive control will be done using aerosolized blood from the same samples. The results from this study, whether positive or negative, will important implications. If positive, it will have a critical and direct impact on ensuring the safety of healthcare workers performing procedures on patients. Procedures using cautery will continue to require high level protection if the COVID status of the patient is unknown. If negative, it will significantly improve the ability of our healthcare system to perform surgical procedures safely and effectively, and conserving critical protective equipment for cases that need it.",2020,2020,Western University,63750,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control",Environmental stability of pathogen | IPC in health care settings,2020 +C03111,172714,General and Inexpensive Saliva-based Viral RNA Testing by Direct Imaging,"Existing nucleic-acid-based COVID-19 tests use enzymes to amplify low-copy number RNA to detectable levels. This adds cost, complexity and time to viral detection. In this proposal we will image fluorescently labeled probes hybridized to individual SARS-CoV-2 genomic RNA strands to enable a robust and highly sensitive test. The detection system involves three key steps: 1. Sample stabilization: As the assay does not require enzymes, robust stabilization of samples derived from saliva or nasal swabs is dramatically simplified. Detergents and mild denaturants will release viral RNA and homogenize any cell debris while serving to minimize virulence. 2. Hybridization and Washing: Probes within the stabilization solution will hybridize to viral RNA, brightly labeling it with quantum dots. Control RNA, such as human 18S RNA, will be similarly labelled but in a different colour channel. Sample preparation will be as simple as spitting into a sealable reagent container and shaking. A glass slide derivatized with viral and control probe oligonucleotides will then be introduced into the container and incubated for a defined time to immobilize the fluorescently tagged RNAs onto the slide as individual molecules. After hybridization, the slide will be rinsed stringently and placed into an imager. 3. Single molecule imaging. An inexpensive (target cost <$50) and easily mass-produced microscope will be designed to attach to a cell phone for single-molecule imaging. Images will be analyzed and uploaded to a medical site for analysis. Additional advantages over conventional tests include long-term storage and shipping for a test that is rapid (<15 min) and simple for point-of-care use. The test can be easily adapted to other RNA viruses, allowing a suite of tests to be rapidly deployed. This technology has the potential to revolutionize viral testing in remote locations, the home, and clinical settings to the benefit of all Canadians.",2020,2020,Simon Fraser University,61519.5,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Michael Smith Foundation for Health Research,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03112,172662,Transitions to a new normal: The health of young children in the Maritimes during COVID-19,"The efforts of parents/caregivers are essential to control the spread of COVID-19 and to ensure supportive environments for young children's health. The states of emergency established in the Maritime provinces from COVID-19 have led to closures to many services for families with young children, the enforcement of physical distancing principles and abrupt changes to employment conditions and income; therefore, shifting the balance of responsibility on families. The level of risk associated with disruption to family life impacting children's health and development is unknown as families manage unpredictable challenges while following government and health directives. This research aims to understand how Maritime families with young children (0 to 8 years), are being impacted and manage family life during the COVID-19 global pandemic. Baseline data on family adjustment already collected provides a foundation for this proposed study that will explore adaptation to family life as the conditions of COVID-19 change to reflect unique timelines of the spread and management of the disease across three provinces. Followed by an initial survey of more than 2200 respondents, the second phase will include a repeat survey and opportunity for families to participate in telephone interviews designed to better understand the adjustments and adaptations to family life over time. The need to study family life during this changing time is critical to provide well-timed, relevant information on the resources needed to support early childhood development and health and mitigate the potential impacts now and into the future. Policy interventions targeting the needs of young families are necessary to ensure success of public health measures to prevent and manage COVID-19. Ongoing engagement with decision makers will advance the dissemination of the results and development of resources and supports for families with young children.",2020,2020,Mount Saint Vincent University (Halifax) Child and Youth Studies,60000,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03113,172862,"Frailty & the Incidence and Course of COVID-19 among 500,000 Older Adults in the UK BIOBANK","From https://www.cfn-nce.ca/project/frailty-the-incidence-and-course-of-covid-19-among-500000-older-adults-in-the-uk-biobank/ : n the absence of any available vaccine or cure for COVID-19, it is of utmost importance to develop improved screening techniques to correctly identify those most likely to develop severe illness and die from the disease. Many determinants, including genetic predisposition, nutrition, social, economic, health behaviours, chronic comorbid health conditions, and environmental factors, contribute to communicable diseases1 such as COVID-19. However, there is limited understanding of the relative importance of the individual and synergistic contributions of these determinants in relation to COVID-19. The majority of these factors are also associated with frailty. Older adults, particularly those living with frailty, are at high risk of hospitalization and death due to COVID-19. In addition to older age, the Centers for Disease Control and Prevention (CDC) have identified several other factors associated with higher risk of severe illness from COVID-19 including disabilities, a medical history of Chronic Obstructive Pulmonary Disease (COPD), asthma, heart conditions, diabetes, chronic kidney disease, liver disease, HIV/AIDS, obesity, and prolonged use of medications such as corticosteroids. Other characteristics that have been proposed as potential, but not yet established, risk factors include type A blood, low vitamin D blood levels, Black race, and some genetic variants (e.g., genes coding for receptors of the cell surface protein angiotensin-converting enzyme 2 (ACE2) may increase access of the coronavirus to airway cells) Very little research attention has been paid to the potential risks associated with socio-demographic characteristics such as poverty and lack of social support, nutrient intake and other health behaviours, as well as environmental risk factors such as air pollution, neighborhood deprivation, and lack of neighborhood green space. We hypothesize that there is a wide range of interacting factors associated with the incidence and progression of COVID-19 among older adults living with frailty and that these may differ from risk factors among those living without frailty. Studies to date have been limited by small samples and retrospective data collection as opposed to drawing upon methodologically stronger, large, prospective studies. Without robust data, health professionals are unable to quickly and accurately identify the most vulnerable individuals for screening and targeted intervention. Our proposed innovative analyses will also search for and identify novel protective factors that improve disease prognosis in mid-age and older adults who are frail. We propose to use the UK Biobank (UKB), a prospective cohort study of unprecedented depth and quality that started in 2006 with 500,000 British middle-age and older adults (currently aged 50-83), to examine how frailty, genetic predisposition, socio-demographic characteristics, health-related determinants, and environmental factors contribute to the incidence and prognosis of COVID-19. The UK government has invested more than $370 million CAD in gathering extensive information on half a million participants' health and life course trajectories over the past 14 years. The secondary analyses we are proposing will leverage that investment to provide a cost-effective, comprehensive, prospective analysis to identify causal, risk, and protective factors associated with the incidence and prognosis of COVID-19 among frail older adults and their non-frail peers. ",2020,2022,University of Toronto,41446.5,Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03114,171734,Digital Health Solutions to Support Women with Addiction During COVID-19: Applying a Gender- and Trauma-Informed Lens,"The COVID-19 global pandemic has had extensive impacts on the mental health and substance use of Canadians. The healthcare system has rapidly adapted current models of care, primarily through the use of digital health platforms and supports. Digital health resources for women with substance use difficulties are critical during this time. Current guidelines have highlighted the importance of gender- and trauma-informed treatment of addiction in women. The goal of the current project is to evaluate whether existing digital health resources for addiction uphold gender- and trauma-informed principles, and to identify needs or opportunities to adapt and/or implement these resources. The current project therefore promises to build capacity in the healthcare system to support women with addiction, who face unique barriers to care. First, we will conduct a Rapid Review to evaluate the evidence for digital health resources for addiction, in those who identify as women and/or who disclose a history of trauma. Second, we will evaluate the degree to which digital health resources for addiction can be characterized as gender- and trauma-informed. A Final Report and Knowledge Mobilization Plan, including a high level summary of resources with strong gender- and trauma-informed principles and a series of recommendations for next steps in service development and implementation, will be shared with knowledge users. A Knowledge User Needs Assessment will then refine these materials. In conclusion, in addition to developing a review and database of digital health resources for women with addiction, this work will highlight digital health gaps and potential gender inequities, providing an opportunity for the adaptation of digital tools or the development of new virtual programming in this area. In essence, this proposal will bring together best practices in virtual care with best practices in trauma and addictions care for women, for immediate use during the COVID-19 global pandemic.",2020,2020,Centre for Addiction and Mental Health (Toronto),37500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Gender,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03115,Supplement to P00038,Sex as a Biological Variable Supplement - Identification of biomarkers that predict severity of COVID-19 patients,"The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are overwhelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.",2020,2021,Dalhousie University,37500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe | Western Pacific,,,,Canada,China | Viet Nam | Spain | Italy | Mozambique | Sudan | Ethiopia | Egypt | Morocco | Cote d'Ivoire | Canada,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C03116,171738,Examining the Efficacy of Evidence-Based Psychosocial Interventions for Schizophrenia-Spectrum Disorders Delivered Through Virtual Care,"Schizophrenia-spectrum disorders are the most persistent and debilitating mental health disorders. Individuals with severe mental illnesses such as schizophrenia-spectrum disorders are among those projected to experience the most negative effects to well-being from the COVID-19 pandemic. Ongoing clinical services have largely been discontinued due to social contact restrictions and access to in-person care has been suspended in most regions. In efforts to maintain clinical services, many programs have turned to virtual delivery of mental health services. However, there is little evidence to suggest which interventions can be effectively delivered through virtual care, and which are only effective when delivered in-person. Due to research suggesting that some interventions can actually cause harm when delivered virtually, and the increasing need for virtual services, it is imperative that we understand which evidence-based treatments should be offered virtually and which should not. The proposed project will conduct a rapid scoping review, meta-analysis, and survey of experts and service-users to determine the efficacy of virtual delivery of ten evidence-based interventions for schizophrenia-spectrums. These results will be disseminated to local and national partners to inform priorities for future research and guidelines for providing virtual care.",2020,2020,University of Toronto,37500,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +C03117,Supplement to P00197,Sex as a Biological Variable Supplement - Shutting down emerging Coronaviruses in humans now and in the future,"In December 2019, a pneumonia associated with the 2019 novel coronavirus SARS-CoV-2 emerged in Wuhan, China. This disease is now named COVID-19. Over 73,000 people have been infected worldwide and over 1,700 people have died from the disease. There is no sign that the rate of new infections and deaths are levelling off or showing signs of declining. Similar coronavirus outbreaks in the future are always a risk and must be addressed now. The goal of this proposal is to establish and test an effective vaccine for SARS-CoV-2. In addition, we will develop a coronavirus vaccine bank containing hundreds to thousands of potential vaccines that can be used at the start of the next coronavirus outbreak. This will give us a head start in trying to treat patients early with the goal of reducing the spread of the disease and subsequent fatalities.",2020,2021,Western University,37500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C03118,supplement to P00187,Sex as a Biological Variable Supplement - Neutralizing human-derived single-chain antibodies against SARS-CoV-2,"SARS-CoV-2 is a virus that has caused an epidemic of human respiratory disease (COVID-19). It first emerged from the city of Wuhan in Hubei in December 2019 and has since spread widely in China and to more than 24 counties globally. The virus has been declared as a deadly global threat, and accelerated international efforts have been engaged to control the virus. A total of 1,524 deaths been confirmed as of 15th February 2020 (WHO). As a result of the rapid transmission internationally, a global call to control the spread of the virus in affected and non-affected areas has been implemented. Currently, there is no effective treatment or vaccine to control the virus. Symptoms of the infection include respiratory symptoms, fever, cough, and shortness of breath. In more severe cases, the infection can cause respiratory failure, severe acute respiratory syndrome, kidney failure, and death. The objectives of this application are 1) to develop antibodies that will block the entrance of the virus into the cells, and to test the efficacy of these antibodies in mice.",2020,2021,University of British Columbia,37500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03119,171730,Niikaniganaw (All My Relations) II - the COVID-19 Rapid Response: Indigenous approaches to synthesizing knowledge for culturally-safe and stigma free mental health care for under-served Indigenous communities in Ottawa-Gatineau,"Developing capacity for stigma free and culturally safe care in health and social service providers is an urgent and critical need in Ottawa-Gatineau. The Niikaniganaw model outlined in Phase 1 (CIHR catalyst grant, 2018) and 2 (CIHR operating grant HIV/AIDS CBR, 2020) is designed to address this need in existing health and social service providers. We are also committed to building capacity for stigma free and culturally safe care in students who will be the future health or social service professionals. In this COVID-19 rapid response grant, we will focus on the following questions: 1) How is COVID-19 affecting the mental health of Indigenous community members in Ottawa-Gatineau who are living with or affected by HIV or related issues, such as substance use, mental illness, poverty, or homelessness? How are they receiving / adapting to the standard public health messaging? 2)What is the effect of COVID-19 on the mental health of health and social service providers who serve these communities? 3)What does culturally-safe and stigma free care in health and social services look like in the age of COVID-19, and by extension, future pandemics or remote / isolated environments? 4)How can we develop capacity for culturally-safe and stigma free mental health care for under-served Indigenous communities in Ottawa-Gatineau in the context of COVID-19? Building from previous experience and existing relationships with university academics, community partners, NGOs, social and health services providers, indigenous and non-indigenous, we will adapt the Niikaniganaw model to the COVID-19 context, and offer 'virtual' sharing circles and ceremonies to answer these questions. These sharing circles will be co-facilitated by researchers and Indigenous Knowledge Carriers. We will document and evaluate the challenges and opportunities of providing virtual sharing circles and ceremonies in real world with indigenous approaches of synthesizing knowledge and healing.",2020,2020,University of Ottawa School of Nursing,37500,Human Populations,Other,Unspecified,Unspecified,Drug users | Indigenous People | Other,Social Workers | Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Community engagement | Institutional level capacity strengthening,2020 +C03120,171703,"Mental Health during the COVID-19 Pandemic: A Living Systematic Review of Mental Health Burden, Factors Associated with Mental Health Outcomes, and Intervention Effectiveness in the General Population and Vulnerable Populations","There will be serious mental health implications from COVID-19 that extend beyond the outbreak for many people. Addressing mental health needs requires understanding the nature and extent of mental health ramifications, factors associated with vulnerability, and evidence on effectiveness of interventions that may be rapidly employed to prevent or address mental health concerns. There is little evidence from prior outbreaks to build upon. Studies from COVID-19 are published rapidly, but many are of dubious quality. Thus, curation of this growing evidence base is urgently needed to provide practitioners and policy makers with clear, coherent evidence synthesis. Living systematic reviews are systematic reviews that are continually updated and provide ongoing access to results via online publication. They are logistically challenging, but provide value beyond conventional systematic reviews in situations where (1) important decisions need to be made; (2) uncertainty in existing evidence poses a barrier to decision-making; and (3) new evidence is emerging rapidly. Such a review is urgently needed to guide mental health care during and following COVID-19. Our research team has expertise in high-impact evidence synthesis research (https://www.depressd.ca/teammembers). Our protocol has been made public on the Open Science Framework (https://osf.io/96csg/). An editorial on the project has been published and will be indexed in major search databases to announce that the living systematic review will provide ongoing, rigorous curation of COVID-19 mental health evidence. We have already launched initial database searches, are receiving daily search updates, and have already reviewed almost 4,000 article citations. We have published initial evidence online (https://www.depressd.ca/covid-19-mental-health). Funding is needed to fully include Chinese-language evidence, synthesize and prepare running briefs of evidence on vulnerable populations, and for continuous web updates.",2020,2020,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General Psychiatry,37500,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03121,171728,The relationship between social connectedness and mental health for residents of long-term care homes: knowledge synthesis and mobilization,"Coronavirus (COVID-19) has taken a particularly heavy toll among people living in long-term care (LTC) homes; they make up more than half of COVID-19 deaths in Canada. But the measures put in place to protect their physical health - such as prohibiting visitors and contact with other residents and staff - is also impacting their social connectedness. What has this done to their mental health? And how can we mitigate the negative impact? This knowledge synthesis was designed to provide high quality, timely evidence that helps answer these questions and responds to the immediate needs of people living in LTC homes, their families and the people who work with them. Our team, composed of researchers as well as people with direct experience of living and working in LTC homes, will identify and synthesize research studies that have examined the impact of social connectedness on mental health for people living in LTC homes. We will also identify studies that looked at ways to maintain social connectedness and try to pinpoint which ones could be useful during COVID-19 as well as other future outbreaks. Our partners will use these results to inform practice and empower LTC home residents and family to advocate for LTC home policies and practices. Our research team will use this knowledge to inform future studies. Our shared goal is to improve the mental health and well-being of people living in LTC homes.",2020,2020,Toronto Rehabilitation Institute-UHN,37500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03122,171711,Converging epidemics and the health of people who use drugs: Using evidence to move decision making into action in the context of COVID-19,"People who use drugs are stigmatized and discriminated against and disproportionately affected by HIV and other STBBIs and experience barriers to testing, treatment, and care. The COVID-19 pandemic has already reduced the availability of harm reduction programming and services which provide access to new injection equipment, HIV/STBBI information and resources, and peer support. The COVID-19 pandemic may result in increased drug and sexual risk-taking for persons with reduced access to their regular supply of drugs and related options (e.g., reduced ability to negotiate condom use in transactional sex, need to share limited injection equipment). The team is comprised of HIV, HCV, and harm reduction researchers, clinicians, legal and policy experts, and persons with lived experience of substance use. Collectively we are interested in responding to the needs of people who use drugs and understanding the impact of the COVID-19 pandemic on them and their communities. Project partners include the Canadian Association of People Who Use Drugs, the Canadian HIV/AIDS Legal Network, and the Canadian AIDS Information Exchange. We will undertake a series of knowledge synthesis activities which include reviewing literature about other relevant health emergencies and pandemics which can help us understand how to respond to COVID-19 and support people who use drugs, bringing together experts to deliberate on the evidence, and producing useful resources for researchers, clinicians and service providers, people who use drugs, and policymakers.",2020,2020,University of Windsor (Social Work),37500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03123,171719,Rapid review of the impacts of 'Big Events' on people who use drugs and delivery of harm reduction and drug treatment services: Implications for strengthening systems in response to COVID-19,"""Big Events"" are significant disruptions (e.g. natural disasters) that create social instability and increase vulnerability to drug-related harms. The COVID-19 pandemic has the potential for significant short- and long-term impacts on risks and harms for people who use drugs, and harm reduction and drug treatment providers will need to be equipped to respond appropriately. This project is a rapid review of the impact of Big Events on drug-related risk and harms, and delivery of harm reduction and drug treatment services. We will identify previous research on the impacts of Big Events, and identify strategies and opportunities for harm reduction and drug treatment services to respond to the COVID-19 pandemic. We will use a variety of activities to disseminate findings and encourage rapid uptake into policy and practice, including an infographic, webinar, press release, and articles for the relevant workforce and people who use drugs. As well as informing the COVID-19 response, findings will provide insights to support strengthening health services and systems to respond to future disruptions.",2020,2020,Centre hospitalier de l'Université de Montréal (CHUM) Family Medicine and Emergency Medicine,37500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03124,171733,A COVID-19 rapid evidence synthesis service to support Ontario's Mental Health and Addictions Centre of Excellence,"Mental health decision makers in Ontario need to have rapid access to evidence to inform decisions during the COVID-19 response. We will initiate a rapid evidence service based on a partnership with Ontario's Mental Health and Addictions Centre of Excellence. In response to questions posed by the Centre and the Ontario Mental Health and Addictions COVID Response Table, we will rapidly produce a mix of two types of synthesis products over the grant period: 1) rapid evidence profiles (completed in three hours, to address emergent questions); and 2) rapid evidence syntheses (completed in three, 10 or 30 days, to address increasingly complex questions). The relative mix of product types produced will be demand driven and responsive to the evolving needs. Rapid evidence profiles will draw on a process piloted by COVID-END and will make use of COVID-END's guide to evidence sources. Rapid syntheses will involve a search of databases of systematic reviews, with longer syntheses also including single studies and key informant interviews, following the McMaster Health Forum's well-established processes. Some high-priority topics will be identified as ""living documents"" and updated regularly. We will share findings directly with partners at the Centre of Excellence, the Response Table, and with an existing provincial network for COVID-19 evidence synthesis. All products will also be publicly available through our website. We will support other grant recipients through webinars to share tools and tips developed through COVID-END that can help to jump-start their synthesis activities and convene conversations to explore how synthesis products across research teams can be shared with researchers and decisions makers in other provinces or territories. The availability of a flexible synthesis service can ensure that mental health policy in Ontario continues to be evidence-informed throughout the COVID-19 response and can benefit from expertise elsewhere in Canada and globally.",2020,2020,McMaster University,37500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03125,171716,"What are the repercussions of the COVID-19 pandemic on the mental health of children aged 5-12, and what are the specific issues for children with disabilities or with chronic illness? A scoping review of the problems experienced and promising avenues of intervention","Le COVID-19 a eu un impact sur le quotidien de tous, incluant les enfants d'age scolaire primaire de 5 a 12 qui peuvent souffrir de stress et d'anxiete. Certains enfants pourraient etre davantage a risque de problemes de sante mentale, dont ceux ayant un handicap ou des maladies chroniques. Nous savons que ces enfants peuvent etre plus a risque de problemes de sante mentale que leurs pairs, et le confinement, la diminution des services presentiels et les changements de routine peuvent avoir un impact importants sur eux. Cette etude fera une synthese des connaissances au sujet des repercussions de la pandemie du COVID-19 sur l'ensemble des enfants de 5 a 12 ans, en faisant ressortir les impacts particuliers chez les eleves ayant un handicap ou une maladie chronique. L'etude explorera egalement les facteurs de risque et de protection de sante mentale des enfants, ainsi que les pistes d'intervention prometteuses afin de favoriser une meilleure sante mentale chez ces jeunes. La question qui guidera la synthese des connaissances sera la suivante : Quelles sont les repercussions de la pandemie sur la sante mentale des enfants d'age 5-12 ans, et quels sont les enjeux particuliers pour les enfants handicapes ou ayant une maladie chronique ? L'information pertinente sera extraite des ecrits scientifiques et de differents rapports. L'information sera analysee avec un comite de partenaires incluant des familles et intervenants de la sante et des services sociaux. Une consultation sera realisee afin d'ancrer les resultats de la synthese des connaissances dans le contexte quebecois. Les recommendations de l'etude permettront de soutenir la sante mentale de l'ensemble des enfants canadiens de 5 a 12 ans et des actions concretes au Quebec en lien avec le confinement et le retour a l'ecole. Une attention particuliere sera portee aux enfants ayant un handicap ou une maladie chronique afin de favoriser l'equite en sante.",2020,2020,Université de Sherbrooke,37500,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03126,Supplement to P00179,Sex as a Biological Variable Supplement - Augmented Discovery of Potential Inhibitors of SARS-CoV-2 3CL Protease,"The COVID-19 epidemic is causing serious or even fatal respiratory tract infections around the city of Wuhan, China and other countries. The urgent situation is pressing the global community to respond rapidly together to develop a vaccine or small molecule drug to inhibit viral infection. We have recently established a powerful Deep-Learning accelerated Docking pipeline to virtually screen a commercial 1.3-billion-compound library in a matter of one week--compared to the three years with previous programs. We have applied this novel algorithm to identify 1000 quality ""candidate"" compounds to inhibit the SARS-CoV-2 main protease (3CLpro) which is uniquely critical for the viral life cycle. We will screen these compounds with a high throughput screening biochemical assay and then evaluate these hits using a cell-based SARS-CoV-2 viral replication assay in a Canadian Containment Level 3 facilty at University of British Columbia. In addition we will use X-ray crystallography to refine the protease 3D crystal structure to accelerate the development of COVID-19 therapeutic drug development. Our research program will significantly contribute to global response to the COVID-19 outbreak by rapidly identifying small anti-viral drug molecules in an extremely condensed timeframe. Our expertise, facilities, and capabilities in cutting-edge Artificial Intelligence, inhibitor modeling, X-ray crystallography, coronavirus protease inhibition, human viral pathogen research, and anti-viral therapeutics are world class. Our first application this month of ""Deep Docking"" enabled the screening of 1.3B commercially available compounds against the essential SARS-CoV-2 protease, in 1 week compared to the 3 years of conventional docking. This accomplishment coupled with fast tracking anti-viral assays at UBC and high resolution 3D structure characterization provide our team, Canadians and global colleagues an enormous head start on developing an anti-viral therapeutic for COVID-19",2020,2021,University of British Columbia,37500,Human Populations,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C03127,171720,Digital Interventions to Support Population Mental Health During and After the COVID-19 Pandemic: A Knowledge Synthesis,"Twenty percent of Canadians, or some 7 million people, will experience a mental illness in any year. This number is anticipated to rise as a result of the COVID-19 crisis. However, the available mental health services are not adequate to support this volume of people through conventional services such as face-to-face care; and, during the time of COVID-19, nor is it appropriate or feasible to do so. Population-based interventions are increasingly needed as a way of reducing the potential mental health impacts experienced by Canadians as a result of job loss, social isolation, changes to everyday life, both now and into the foreseeable future. The purpose of this study is to synthesize and mobilize knowledge related to digital interventions that could support population mental health during and after COVID-19 in Canada, and could be leveraged by the general population. We will also identify strengths, weaknesses and gaps that are applicable to the COVID-19 context. By digital interventions, we refer to websites, web-based programs, electronic knowledge platforms, mobile health apps (inclusive of texting), telemedicine and social media that could be used during COVID-19 to support mental health, but were not necessarily designed for this purpose. This study will be done in two phases. Phase 1 will consist of a rapid review of academic and grey literature. In Phase 2, an environmental scan of experts and knowledge users (inclusive of people with lived experience of mental illness) will occur as an embedded knowledge mobilization strategy. Other knowledge mobilization activities will occur after both phases conclude.",2020,2020,Centre for Addiction and Mental Health (Toronto),37500,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C03128,171706,"A COVID-19 Patient Oriented Response and Recovery Effort: Working Across Sectors to Aid Healthcare Providers Suffering from Burnout, PTSD, or Treatment Resistant Depression (TRD)","Workplace stress can lead to burnout, post-traumatic stress disorder (PTSD), and treatment resistant depression which affects morale, absenteeism, retention, and patient care. The mental health of healthcare providers is understudied and inadequately supported, especially given the current pandemic. Starting with a robust knowledge synthesis process, our team will both examine and address workplace mental health wellness among healthcare providers and the community. The relationship between ketamine and the brain-behaviour relationships implicated in PTSD and treatment resistant depression is well supported and scientists have identified the therapeutic effects of ketamine may be potentiated by enhancing resiliency-based therapies. The focus of this application is a combination therapy involving the implementation of a successful evidence-informed resilience curriculum, Roots to Thrive (RTT) and Ketamine-assisted Psychotherapy (KAP). Our team aims to capitalize on the potential synergy of these two interventions and build on current treatment protocol inefficiencies to provide a novel, evidence-based, and sustainable intervention for PTSD and/or treatment resistant depression among healthcare professionals. RTT has undergone two successful pilots, demonstrating statistically significant impact on wellness traits of the participants. Ketamine is an FDA-approved drug. It's off-label use for treatment resistant depression and PTSD has been described as the single most important advance in the treatment of depression in over fifty years. We are collaborating with policy makers, researchers, and clinicians who have experience with this treatment. Beginning with healthcare providers in need (as team members and patients), our team will examine and synthesize knowledge through a literature review, protocol development, and evaluation plan, all of which will support program development and a study of this novel intervention for PTSD and/or treatment resistant depression.",2020,2020,Vancouver Island University (Nursing),37500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03129,171747,Interventions to Mitigate COVID-19 Related Mental Health Risks for Those With Pre-Existing Chronic Health Conditions and Facing Social and Economic Barriers: A Scoping and Rapid Realist Review,"There is an urgent need to provide good evidence that will support mental health and substance use care related to COVID-19, especially for those who are at risk of infection. Examples of groups of people who would most benefit from this evidence include those with mental health, cognition, and physical health concerns. In addition, within these groups are people who face different social and financial barriers that are even higher risk for mental health concerns related to COVID-19. There is a lot of different information which is being shared among researchers and health professionals, however, it needs to be carefully evaluated and combined in order to be more meaningful to those who need it. The purpose of our project is to conduct a structured literature search to identify promising programs and policies. The results will be used to develop resources that will help to reduce mental health issues related to COVID 19 infection and recovery for different people. We will work with experts in mental health who develop policies and programs for mental health care in Canada. They will guide our literature search and how to report and distribute the findings. In addition to these experts we will be guided by people who have recovered from COVID-19. We will use a well established approach referred to as a rapid realist review in order to find out what types of program and policies would work for different types of people and in different situations. We will make recommendations to help address the mental health care needs of different at-risk populations and share our information with other researchers, those in health practice, and the general public. The results of this project will help to provide information that is relevant to researchers, health professionals, and the general public. It is one important step that can help manage the COVID-19 pandemic and future effects of similar disease outbreaks.",2020,2020,Kwantlen Polytechnic University,37500,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03130,Supplement to P00053,Sex as a Biological Variable Supplement - Animal models for SARS-CoV-2: vaccines and immune enhancement,"In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. In less than two months, there have been over 69,000 cases and over 1600 deaths. Quarantine measures have been imposed on entire cities in China in an attempt to control spread. Cases of SARS-CoV-2 have been identified in 28 other countries and there is concern that this could lead to global pandemic. Here we propose to identify what common lab and agricultural animals may be infected with SARS-CoV-2. This addresses two important questions. What animals can be infected and may pose a risk (or are at risk) and can these animals be used to models. Animal model allow us to understand how the virus causes disease, whether vaccines can be developed that protect from disease and how might the virus be transmitted. These are critical questions that need to be addressed when a new pathogen emerges. In addition, there is some concern that less than optimal vaccines or previous exposure to related pathogens could exaserbate disease - this is a somewhat unique phenomenom that was observed with SARS-CoV vaccines. We plan to investigate whether these animal models can be used to test for this, to ensure that vaccines are safe prior to testing in human clinical trials",2020,2021,University of Saskatchewan,37500,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Animal source and routes of transmission,2020 +C03131,171722,Depression In community Residing Elders (DIRE): A Rapid Review and Network Meta-Analysis of Depression Telemedicine Treatments for Older Adults Living in the Community.,"Depression is the single most common mental illness in older adults and it leads to significant struggle day to day. Older adults experiencing depressive symptoms, such as low mood, are often under treated. One reason for under treatment is difficulty accessing treatment. Social isolation worsens low mood, and many other symptoms of depression. There are virtual or telemedicine approaches using phones or computers, that healthcare providers can use to provide treatments for depression in older adults. During the COVID-19 pandemic, older adults are even more socially isolated and less able to seek care. This vicious cycle contributes to poor outcomes for society's most vulnerable members. Our goal is to determine what telemedicine strategies are available for older adults with depression, and which are most effective in reducing symptoms. We will do this by reviewing all the existing studies in scientific research. Through analysing these studies we will be able to determine which treatments work best for patients. Knowing which treatments are best will allow us to inform patients, doctors, and health care teams how to best use these services to help reduce the burden of depression in older adults.",2020,2020,University of Calgary Medicine,37500,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03132,Supplement to P00181,Sex as a Biological Variable Supplement - Host cellular protein substrates of SARS-CoV-2 proteases,"The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to COVID-19 disease in China and worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Currently, the pathogenic mechanisms that lead to COVID-19 and related SARS/MERS-CoV diseases are not understood. In this study, we will identify the host proteins that are targeted by a viral protein called a protease using an unbiased proteomics approach. Identifying the protein targets of SARS/MERS-CoV proteases will reveal into the protein sequence that binds to the proteases. We will engineer and optimize decoy protein sequences that will effectively block SARS/MERS-CoV protease function and thus, inhibit SARS/MERS-CoV infection. Uncovering the proteins that are targeted by the SARS/MERS-CoV proteases will also provide a catalog of the host processes that these viruses affect, thus gaining insights into the pathogenic mechanisms that lead to COVID-19 disease.",2020,2021,University of British Columbia,37500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Phase 1 clinical trial",2020 +C03133,Supplement to P00172,Sex as a Biological Variable Supplement - Reducing the Health Care Resource Burden from COVID-19 (SARS-CoV-2): Rapid Diagnostics to Risk-Stratify for Severity of Illness,"Key to an effective response to the current novel coronavirus (COVID-19) outbreak is a method to rapidly identify emergency department patients presenting with symptoms of COVID-19 and are at high risk of progressing to severe illness and death. At University Health Network, our team represents a deeply experienced group of critical care doctors and infectious disease researchers who can immediately respond to the global need to provide an accurate diagnosis of respiratory illness-the main feature of COVID-19-at the front lines of patient care. We have recently developed a 40 minute diagnostic test to determine lung quality for transplantation. Recent scientific studies from China clearly show that the body's development of respiratory distress as a response to potential COVID-19 infection produces an identical injury profile that would be detected by our diagnostic test. We will work alongside SQI Diagnostics, our Canadian partner committed to developing diagnostics for lung health, to adapt our test towards the development of RALI-Dx (Rapid Acute Lung Injury Diagnostic). This diagnostic can be used by hospital emergency departments to screen for lung sickness and the likelihood of COVID-19 infection. An important part of our CIHR-supported research study is a commitment from our Chinese collaborators to safely test our diagnostic first on COVID-19+ blood samples to make sure the test is highly accurate before hospital use. With our 40 minute RALI-Dx test, we will: -Quickly identify the highest risk patients in need of immediate care -Identify lower risk patients who require at-home monitoring -Reduce the current major stress on health care facilities Additionally, new COVID-19 therapies are being rapidly developed around the world, and the first step will be to identify which patients will benefit the most from these treatments. With RALI-Dx, hospitals everywhere can better manage patient care and provide an accelerated response to the COVID-19 outbreak.",2020,2021,University Health Network,37500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +C03134,171710,Remote cognitive assessment in severe mental illness: A scoping review,"Schizophrenia and related psychoses are arguably the most serious of all mental disorders, imposing enormous burden on individuals, families, and communities. In addition to symptom recurrence or relapse and deterioration in social functioning, most individuals also present with cognitive impairments (difficulties in verbal memory, executive functioning, attention). These impairments represent important psychological intervention targets. Specifically, cognitive remediation therapy(CRT) and meta-cognitive training (MCT) have been shown to improve these cognitive dimensions, in addition to psychotic symptoms, insight, and self-esteem. Brain imaging evidence additionally suggests that CRT and MCT improve brain function. However, the current COVID-19 pandemic has caused a significant barrier to accessing mental health services, which increases risk of relapse, ER visits, and hospitalizations. Hence, we are working to deliver these psychological interventions remotely using digital mental health technology. We plan to conduct a scoping review of the current literature on remote cognitive assessment to determine best practices in this field. To achieve this, we propose to: 1) map the current knowledge on remote cognitive assessment for severe mental illness; 2) identify potential barriers and facilitators; and 3) compare knowledge regarding remote cognitive assessment for severe mental illness with neurological and geriatric populations. Our national collaborative initiative is intended as a rapid response to the COVID-19 situation for populations with serious mental illness. Our scoping review will facilitate the work of researchers, clinicians, and policy makers whose aim is to develop digital health and technology-based interventions for cognitive health. Our findings will be widely available to the Canadian community, as we will establish a knowledge-user and stakeholder consultation group comprised of organizational leaders, patients, and caregiver representatives.",2020,2020,CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital,37500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03135,"170342, 171485, 175492","Preventing SARS-CoV-2 infection by targeting human type II transmembrane serine protease activity [Added: Sex as a Biological Variable Supplement, COVID-19 Variant Supplement]","The SARS-CoV-2 coronavirus causing COVID-19 has been declared a global emergency by the World Health Organization which has mobilized international scientists to collaborate in order to find therapies to counteract the virus's effects which can be devastating. The strategies need to be as vast as possible since we do not yet know if vaccines or other antiviral drugs will be efficacious. Our group had previously shown in the context of influenza infection that the human host has cell-surface proteases (called type II transmembrane serine proteases or TTSPs) that the virus requires in order to cleave a viral surface protein called hemagglutinin, itself essential for the virus to gain entry into the cell and further replicate using the host cell machinery. We had shown that small molecules inhibiting the activity of lung epithelial cell proteases were efficacious at significantly reducing influenza virulence demonstrating novel anti-viral properties of the compounds. The situation is similar with the SARS-CoV-2 virus but the protein found on the surface of the virus is different. This protein is called the spike glycoprotein (or S protein) and it requires cleavage by human host cell proteases of the TTSP family for its virulence. Our proposal will test protease inhibitors in models where cells are expressing the S protein and the most potent molecules will then be validated in lung organoids to verify their efficacy at reducing viral propagation. We have put together a team of molecular pharmacologists, chemists and virologist with access to containment level 3 facilities to rapidly assess the potential anti-viral properties of the compounds that we already have on hand. In addition, our team will be supported by Dr. Gary Whittaker, Cornell University, one of the world's experts in coronavirus biology. We believe that these conditions are very favorable for us to have a quick impact in the field and to deliver novel antiviral compounds for patients with COVID-19.",2020,2022,Université de Sherbrooke,727560,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C03136,"170641, 171490, 175495","Understand the high pathogenicity and zoonotic transmission of the COVID-19 virus: evasion of host innate immune responses [Sex as a Biological Variable Supplement, COVID-19 Variant Supplement]","Coronaviruses are not new to humans. The human coronaviruses OC43 and 229E were discovered as early as in the 1960s. Both viruses cause common cold, a mild infection of our upper respiratory tract. However, the story started to change in 2002 when SARS broke out in China and other countries. This outbreak was caused by a new coronavirus which originally came from bats. Most importantly, this SARS coronavirus is highly pathogenic, with a fatality as high as 10%. Ten years later, a more deadly coronavirus caused the MERS outbreak. Now, a new coronavirus came back, is raging in China, may cause a global pandemic if not controlled. This new virus, COVID-19 (or SARS-CoV-2), has infected more and killed more than the total number by both SARS and MERS. Two urgent questions need to be addressed. - How did these coronaviruses transmit from animals into humans? - What have made them so pathogenic and lethal? Humans are protected from viral diseases by the immune system. These pathogenic coronaviruses must have found ways to evade the immune responses so that they can spread in humans and cause fatal illness. We thus propose this research to elucidate how this COVID-19 virus does this. The findings will identify the key viral genes that suppress immune responses by blocking essential signaling pathways. Our results will open new avenues for the development of effective interventions to halt the COVID-19 break.",2020,2022,Lady Davis Institute for Medical Research (Mtl),410500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03137,171707,"Stress, burnout and depression in women in health care during COVID-19 Pandemic: A Rapid Evidence Synthesis","This proposal is submitted in response to the CIHR's call for COVID-19 rapid research funding opportunity in Mental Health and Substance Use. We aim to develop a rapid synthesis of published literature to identify the common causes of stress, burnout, and depression in women in health care during pandemics. This includes professions such as doctors, nurses, pharmacists, therapists, technicians, personnel support workers, community health workers. As part of this review, we will also explore strategies that can prevent serious psychosocial or mental health consequences as a result of these exposures. Women make up four in five health workers in Canada. In addition to their work responsibilities, they are faced with the burden of caring for families and children. Stress, burnout and depression can lead to substance abuse and suicidal ideations. Protecting the mental and emotional health and well-being of healthcare delivery personnel engaged in directly responding to COVID-19 pandemic is important for health workers own health, patient care, and for the viability of health-care systems. This study will inform hospitals, professional societies, and governments with their efforts to provide supporting resources and services health care workers.",2020,2020,"University of Toronto Institute of Health Policy, Management and Evaluation",37500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03138,171742,The effectiveness of virtual interventions targeting mental health in people with chronic musculoskeletal pain: A Systematic Review and Network Meta-Analysis,"Chronic pain in muscles and joints combined with symptoms like anxiety or depression can result from a disease or traumatic injury that does not resolve. Treatments that focus only on the physical or mental health aspects of the problem typically do not work. Treatment approaches that include improving mobility and activity while addressing mental health symptoms have been shown to improve function and quality of life. These treatments are typically provided by multidisciplinary teams using intensive face-to-face outpatient or inpatient services. Lack of system capacity or restrictions placed on non-emergency services during a pandemic can prevent patients living with these disabling problems from getting the treatment they need. This review will summarize studies that tested virtual services such as telemedicine or web-based services to see if they help manage mental health symptoms, mobility, and quality of life in people with persistent musculoskeletal pain and mental health symptoms. We will describe what mechanisms might be driving treatment benefits and describe the type of interventions and platforms that can be used. This information will be combined with patients' treatment preferences and surveys of what strategies were used during the COVID-19 pandemic to map treatment alternatives. Statistical analyses will be used to compare many different types of treatments, to find out which treatments work best. We will compare virtual treatment to no treatment and in-person treatment. We will evaluate how treatments needs and outcomes might differ for men and women. We will use patient preferences, practice surveys, and research findings to make recommendations for better future care during a pandemic.",2020,2020,Western University,37500,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03139,Supplement to P03280,Sex as a Biological Variable Supplement - Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),,2020,2021,"Keenan Research Centre (Toronto, ON)",37500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03140,171740,Mobilizing Knowledge on the Use of Virtual Care Interventions to Provide Trauma-Focused Treatment to Individuals and Families At-Risk of Domestic Violence During COVID-19,"Across the globe, the Coronavirus (Covid-19) pandemic has been linked to increases in domestic violence reports, crisis calls and shelter intakes. COVID-19 has created an unprecedented shift in healthcare systems around the world with the move towards virtual care to limit unnecessary in-person interactions. As care shifts from in-person to virtual visits it's important to examine the application and feasibility of virtual care interventions (e.g., telemedicine, mHealth or videoconferencing) in addressing domestic violence in the current pandemic context. Our proposed application includes a Knowledge Synthesis (KS) phase that involves a rapid review of the evidence on the application and feasibility of a range of virtual care interventions (e.g., telehealth, mobile health apps, videoconferencing) within primary care settings in addressing domestic violence and that incorporate trauma-informed care and support for individuals at-risk and survivors. Our Knowledge Mobilization (KMb) phase will involve a process of knowledge dissemination on potential virtual care interventions adopted within primary care, engaging key actors/partners, and designing a knowledge translation (KT) plan for implementing a feasible intervention.",2020,2020,University of Alberta,37500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery,2020 +C03141,171743,Valuing Indigenous Emotional Wellness -- Reviewing programs to enhance support for children in rural and remote communities,"One of the most sustained consequences of the Covid-19 pandemic will be its impact on emotional wellness (or mental health). Indigenous children at much higher risk of emotional health issues than their non-Indigenous peers. Health leaders must rapidly prepare to manage the emerging emotional health pandemic among Indigenous children. The main goal of this project is to create program resources geared to Indigenous children in rural and remote regions of Canada. This population is uniquely vulnerable, will be heavily impacted by Covid-19 restrictions, and lacks access to health supports that most Canadians take for granted. This project has two phases. In Phase I, we will review all available information on emotional wellness programs. We will: (a) assess each program's relevance to Indigenous children, (b) determine the program's feasibility in the context of rural and remote communities, and (c) document the level of evidence of the program's effectiveness. We are aware that improving the spectrum of services available will be pointless if stigma continues to prevent children from accessing support. Thus, in Phase II, we will create a positive messaging strategy that normalizes and prioritizes emotional health. This project will create new information for leaders, that is grounded in both evidence and culture, tailored for their use and easy to access, including: •tips sheets that summarize information about each program, •a repository of reference materials, and •positive messaging materials to reduce stigma. Our results will inform enhancements to stepped care, support children's emotional wellness, and prevent crises. We will share the results broadly through the www.ACHWM.ca partner portal to aid communities as they work to promote wellness and recovery for school-aged Indigenous children during and following Covid-19.",2020,2020,Laurentian University of Sudbury,37500,Human Populations,Unspecified,Children (1 year to 12 years),Rural Population/Setting,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03142,171726,Family Carers and COVID-19: A Rapid Integrated Mixed Methods Systematic Review,"The overall goal of this project is to develop a population-based program to improve the mental health and well-being in family carers of COVID-19. In order to do this quickly and properly, we have divided our project into two phases. Phase 1 (current proposal) is a 6-month project to summarize the published, unpublished and grey literature related to the mental health and well-being of family carers. Results from Phase 1 will inform Phase 2, which is development of a population-based intervention. We are using the logic model of the Caregiver Support Framework, which is intended to identify gaps and plans for improvements. We are also building on our previous experience and expertise in synthesizing the literature. We will start with a one month broad search of published papers describing the approaches used to improve the mental health and well-being of family carers (i.e., informal or unpaid adult family caregivers over 18 years of age caring for adults or children) during communicable disease outbreaks (e.g., SARS, Ebola, COVID-19). We will present our results in a knowledge map (e.g., visual aid) to describe the age, sex, ethnicity, and geographical spread. Then we will complete two rapid searches of the unpublished and grey literature (e.g., guidelines, policies, websites, public health campaigns) to determine: 1) the mood, thinking, and behaviours (including substance use) of family carers during COVID-19, and 2) how approaches are used to improve the mental health and well-being of family carers during COVID-19. Our knowledge mobilization plan includes updating our knowledge map to include unpublished and grey literature related to COVID-19. We will also integrate the results of the rapid searches and apply these to the logic model of the Caregiver Support Framework. This framework will be used to inform a population-based intervention (Phase 2, future proposal), public/conference presentations, and lay summaries/open access publications.",2020,2020,University of Toronto,37499.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03143,171714,A systematic review on the effectiveness of virtual sleep intervention delivery to improve sleep and mental health outcomes in the post-secondary student population.,"Students pursuing post-secondary education (e.g., college/university) are a population group at risk for both significant sleep problems and poor mental health outcomes such as depression and anxiety. Interventions such as sleep hygiene education and cognitive behavioural therapy (CBT) are commonly used treatment options for sleep problems and have been effective in improving sleep and mental health in the university student population. Digitally-delivered CBT has also shown to be effective in improving sleep in youth, however it has not been evaluated in the post-secondary population. As a result of the COVID-19 pandemic, many industries, including mental health services, were forced to close to comply with physical distancing measures. In an effort to address the growing sleep challenges faced by students, some institutions have moved to providing care through a virtual platform. However, the effectiveness of delivering sleep interventions virtually to the post-secondary population is unknown. Given this paucity of information - especially in a climate that may be forced to embrace virtual care options for service delivery in perpetuity as we slowly enter a 'new normal', we propose a systematic review of the literature to synthesize the best available evidence on the effectiveness of non-pharmacological sleep interventions delivered through a technology-based platform. Our review will provide knowledge users with a synthesis of the best available evidence to inform decision making when developing interventions to be delivered through virtual platforms. Moreover, as the COVID-19 situation develops, this synthesis allows us to be proactive in adapting a new way to deliver mental health services (e.g., virtual care).",2020,2020,University of Ontario Institute of Technology,37499.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03144,171717,"Digital Interventions to Detect, Prevent, and Manage Mental Health Problems in People with Chronic Diseases: Knowledge Synthesis","La pandemie mondiale de COVID-19 touche la majorite des pays et a cause des centaines de milliers de deces jusqu'a maintenant. Consideree comme une catastrophe humanitaire, elle aura de graves impacts sur la sante mentale de la population, surtout les groupes plus vulnerables, dont les personnes ayant des maladies chroniques. Ces individus sont plus a risque de presenter des problemes de sante mentale comme l'anxiete et la depression, risques augmentes par la perte du soutien social et la solitude. S'ils ne sont pas pris en charge, ces problemes peuvent avoir des consequences a long terme sur la sante des personnes et augmenter les couts relies a leur traitement. Des etudes scientifiques ont demontre l'efficacite des interventions en premiere ligne pour ameliorer la prise en charge des problemes de sante mentale chez les personnes vivant avec des maladies chroniques. Cependant, il y a peu de connaissances sur les interventions qui utilisent les technologies numeriques. Dans le contexte de la crise actuelle, ces technologies peuvent etre une solution pertinente pour mieux rejoindre les personnes vivant avec des maladies chroniques et intervenir aupres d'elles. Notre projet permettra de verifier s'il y a des interventions en sante numerique efficaces pour prevenir, depister et prendre en charge les problemes de sante mentale chez les personnes vivant avec des maladies chroniques. Tout d'abord, nous allons consulter des documents qui resument les resultats des recherches sur le sujet. Ensuite, nous allons resumer les connaissances identifiees et les partager avec les partenaires de l'equipe. Enfin, nous allons faire des recherches plus poussees dans la litterature scientifique afin de repondre le plus adequatement aux questions des partenaires. Ce projet va permettre de developper des solutions de sante numerique pour un suivi optimal des problemes de sante mentale chez les personnes atteintes de maladies chroniques, en s'adaptant au contexte de la crise de COVID-19.",2020,2020,Université Laval,37494,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03145,171744,The COVID-19 Pandemic and Eating Disorders in Children and Adolescents: Recommendations from the Canadian Consensus Panel,"The negative impact of COVID-19 and the associated social isolation on mental health has been well-described in terms of heightened anxiety and depression. Literature on the impact on individuals with eating disorders (ED) and their families is only just emerging. In most settings across Canada only urgent outpatient visits or admission to inpatient units are currently permitted, with ambulatory care having been suspended. Given these challenges, we propose to complete a scoping review of the literature and synthesize the knowledge available on the impact of COVID-19, as well as virtual treatments and other online technologies for children and adolescents with EDs and their families in order to develop practice guidelines. Experts in guideline methodology, library science, and EDs have partnered on this knowledge synthesis project which will use several internationally recognized frameworks including the Appraisal of Guidelines, Research, and Evaluation (AGREE II) tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to synthesize and evaluate the evidence. Our team has recently published Canadian Practice Guidelines for treating children and adolescents with EDs and is perfectly positioned to respond to this rapid research funding opportunity. Many of our recommended interventions for children and adolescents with EDs are focused on in-person treatment, which currently cannot be delivered. New recommendations would help clinicians, administrators, and policy-makers to provide the best possible care in these unprecedented times, and ultimately help thousands of Canadians with EDs and their families.",2020,2020,McMaster University Psychiatry & Behavioural Neurosciences,37492.5,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03146,171735,"Harnessing digital mental health to improve equity in mental health care in the context of COVID-19: Needs, best-practices and opportunities in the Asia Pacific region","COVID-19 has had an unprecedented impact worldwide and is expected to have profound mental health effects. The impacts of the pandemic and the changes to regular life all affect mental health. These affects might be more severe for people who experience other challenges or are in particularly stressful circumstances, including healthcare workers, people experiencing homelessness, women, the elderly, children, people living with existing mental health and substance use conditions, and victims of domestic violence. People who are at-risk might also have a more challenging time accessing mental health care. Because the pandemic is global, its affects are felt worldwide. The way that countries respond can provide important lessons for Canada and other parts of the world. The Asia Pacific region includes Canada and is home to 40% of the world's population. Countries in the region have grappled with COVID-19 at different stages and have taken different approaches to addressing mental health. All countries have challenges with making sure that mental health services reach those most at-risk and there is an opportunity to learn from each other. The use of digital mental health care has increased during the pandemic. While digital mental health has potential to improve access to care, there are also challenges with making sure it reaches at-risk groups. This study, led by the APEC Digital Hub for Mental Health, brings together a network of researchers, healthcare providers and policy makers to rapidly synthesize information about the needs of at-risk groups in the Asia Pacific, challenges they face to accessing mental health care, and the possibilities of using digital health to improve their care. We will conduct reviews and consultations with expert groups. The results of these activities will lead to a knowledge mobilization plan that includes recommendations for improving mental health care via digital technology for at-risk groups in the Asia Pacific.",2020,2020,University of British Columbia Psychiatry,37491.75,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03147,171723,"A rapid review of the effects of epidemics or pandemics on suicide, suicidal behaviours and suicidal thoughts","Suicide remains one of the most important public health challenges worldwide, with more than 800,000 people dying every year. The effect of the pandemic, including physical distancing measures, on suicides and suicidal behaviors remains unclear. This proposal aims to gather and present all available evidence for the effect of infectious pandemics on suicide, suicidal behavior and suicidal thoughts. This rapid review will answer the question ""in a population exposed to an infectious epidemic or pandemic, what is the effect on suicides, suicidal behavior and suicidal thinking both during and after the pandemic"". The review will consider this question across all age groups; between men and women; within indigenous populations; those in lower socioeconomic classes; those with pre-existing health conditions (including mental illnesses); and those who have been infected with Covid-19. The review will include all articles found in several electronic databases using predetermined search terms and will be continuously updated. These will be studies published in peer-reviewed journals which address mental health outcomes in an epidemic or pandemic. Papers will not include research related to the epidemic of suicide. Using this review, we hope to provide policymakers with high quality evidence for suicide prevention planning during pandemics. We will also use the review to modify existing guidelines on suicide prevention to be appropriate during times of pandemics and physical distancing. Also, we propose to use this review as a first step in creating a suicide prevention rapid synthesis team with our knowledge users to create ""evidence on tap"". We will create a governance group with our knowledge users to oversee the generation and answering of questions related to Covid-19 and suicide. The review will inform planning for a strategic plan for suicide and Covid-19 research.",2020,2020,Ottawa Hospital Research Institute,37490.25,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People | Individuals with multimorbidity | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03148,171721,Approaches to support mental health of diverse patients on wait lists for procedures delayed by COVID-19,"Due to COVID-19, hospitals across Canada cancelled thousands of procedures for patients with cancer, heart failure and many other conditions. The backlog grows with each week, so even when service resumes, patients will face lengthy waits, and many were waiting for months prior to the pandemic. These patients (and family/care partners), many facing worsening health, are suffering from anxiety, which can further limit physical health and also affect mental health (i.e. depression, substance use, suicide). If untreated, mental health can deteriorate. Clearly, these patients would benefit from approaches (strategies, interventions) to support their mental health. Over the years, many researchers have studied the impact of treatment delays or ""waiting lists"" on patients. We will summarize ten years of waiting list research published pre-pandemic to identify: (1) the mental health impact of waiting on patients with diverse characteristics, and (2) approaches that hospitals can implement to support mental health of wait-listed patients. We will share the results with our research partners including clinicians and health care managers who lead hospitals and professional organizations in Ontario and Canada so that they can: encourage governments to provide resources for mental health support; share the results even more broadly through the Canadian healthcare community; and implement the results in their hospitals. Doing so may alleviate anxiety among the thousands of patients in Canada waiting for healthcare procedures.",2020,2020,University Health Network,37485,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03149,171705,Protecting those who Protect Us: An evaluation and synthesis of resources deployed to support firefighter mental health during COVID-19,"Firefighting is a high-risk occupation that increases firefighters' chances of exposure to transferable diseases as well as witnessing traumatic events. Witnessing traumatic events can increase firefighters' chance of experiencing mental health conditions including post-traumatic stress injury (PTSI), depression, difficulties with alcohol and chronic fatigue. It is known that in periods of heightened risk such as a pandemic, there are further impacts on individuals' mental health. For example, following the severe acute respiratory syndrome (SARS) outbreak in 2003, front-line workers identified this event as traumatic and those who had higher risk for SARS exposure reported more PTSI symptoms than other workers. It would be expected that firefighters would have the same exposure to PTSI and associated mental health conditions during and following the COVID-19 pandemic. Consequently, in addition to known factors that increase firefighters' risk for mental health disorders, COVID-19 has created a unique and challenging context where their risk for experiencing mental health conditions has increased. Our project will use an integrated knowledge translation (KT) approach where firefighters as knowledge users are embedded in the research process. As a team, we will appraise information about managing mental health from three primary sources: i.) peer-reviewed academic journals, ii.) online information specific to firefighter health and general platforms, and iii.) existing guidelines provided by firefighter associations. The results of the appraisal of our knowledge sources will be integrated in a way that will allow comparisons for similarities and differences to ensure the most representative synthesis of knowledge. Results of the synthesis will be communicated using various KT tools including lay summaries, fact sheets, info-graphics, and video vignettes that can be used to develop strategies to help firefighters better manage their mental health and prevent illness.",2020,2020,Lakehead University,37476,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Emergency Responders,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03150,171729,"COVID-19 Physical Distancing and Post-Traumatic Stress Injury: Utilization of Digital Health and Remote Mental Health Services for Military, Veterans, and Public Safety Personnel","Physical distancing arising from COVID-19 has rapidly forced a paradigm shift toward remote mental health (MH) service delivery and a surge in the use of digital health (DH) (e.g., teletherapy/medicine, eHealth, and mHealth). Though limited in use mere weeks ago, DH has become essential for system access, assessment, and treatment. Legal, clinical, cultural, practical, and security considerations, however, remain unaddressed for delivering MH services to trauma-affected populations (TAPs). TAPs include public safety personnel (PSP; e.g., border services, communications officials, correctional workers, firefighters, paramedics, police, etc.), military members, and Veterans struggling with Post-Traumatic Stress Injuries (PTSIs) and other MH concerns that can be associated with or exacerbated by the pandemic. As TAPs may be particularly affected by changes from in-person to digital delivery of MH services, an understanding is needed of: (1) the clinical effectiveness of DH when addressing PTSIs; (2) perspectives of persons with lived experience, MH clinicians, senior leadership and policymakers; (3) the current context, needs, and considerations associated with DH uptake and use; and (4) realistic solutions for effectively delivering DH to TAPs. The HiMARC research team, with its established relationships with PSP, military, and Veteran communities in Alberta and beyond, is well-positioned to conduct a current state and needs analysis through a rapid review and key stakeholder engagements with the aim of synthesizing knowledge of needs, gaps, barriers, and facilitators for DH delivery of PTSI assessment and interventions. A co-designed, multi-phased knowledge mobilization and implementation plan coordinated with national efforts (e.g., CIPSRT and CIMVHR) will be created to deliver safe digital MH services at local, national, and international levels to PSP, military, Veteran, and civilian populations suffering from MH conditions including PTSIs.",2020,2020,University of Alberta Occupational Therapy,37473,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C03151,171741,Securing Safe Supply During COVID-19 and Beyond: Scoping Review and Knowledge Mobilization,"https://cihr-irsc.gc.ca/e/documents/HERDER_Initial-Knowledge-Synthesis_Draft-2020-06-22.pdf Creating a ""safe supply"" of drugs has the potential to reduce a variety of harms suffered by People Who Use Drugs (PWUDs), including non-fatal and fatal overdoses associated with Canada's ongoing opioid crisis. The onset of the COVID-19 pandemic, and related social distancing measures, has complicated PWUDs ability to access the pharmacological substances they need, placing them at increased risk of harm from withdrawal and/or toxicity from unsafe 'street' sources of drugs. In the context of COVID-19, the college of pharmacists has lifted the requirement of triplicate prescriptions for controlled substances, making it easier for physicians and pharmacists to serve people in our public state of emergency. Addiction clinics have also developed more leniency for 'take-home' doses of medication (such as opioid agonist therapy) to encourage social isolation and support people in quarantine. However, access to a safe supply of opioids remains elusive for many PWUDs in Canada for reasons that are presently unclear. Integrating the expertise of PWUDs, clinicians, scientists, and legal scholars, the core aim of our project is to find ways to facilitate access to a safe supply of drugs in the context of the COVID-19. We will: 1) identify best practices for securing a safe supply for PWUDs, focused in part on how ""safe"" supply may be contextually conditioned; and 2) develop a set of recommendations and strategies to encourage the uptake of safe supply across Canada. These will take into account factors including the circumstances of PWUDs who have recently been released from prison and additional challenges related to geography, homelessness, poverty, race, and/or gender. Incorporating the lived experiences and expertise of PWUDs directly into our research, our team's combined medical, scientific, and legal training has the capacity to make sense of-and act upon-the evidence on how to provide access to a safe supply of drugs in the context COVID-19 pandemic and beyond.",2020,2020,"Health Law Institute, Dalhousie University",37464,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03152,171745,Developing a Rational Approach Towards Offering Procedural Interventions (ECT & rTMS) for At Risk Populations in Psychiatry During the COVID-19 Pandemic: An Interdisciplinary Evidence Synthesis.,"The COVID-19 pandemic will associate with parallel mental health pandemics, one during the pandemic and the other after. The mental health impact of COVID-19 will be disproportionately experienced by at risk populations, with increased prevalence of mental illness such as mood disorders where procedural neurostimulation treatments such as Electroconvulsive Therapy (ECT) and repetitive Transcranial Magnetic Stimulation (rTMS) have significant evidence. However, hospitals across the country have either discontinued or decreased ECT and rTMS offerings, procedural aspects remain arbitrary varying from hospital to hospital putting healthcare providers at risk, and there is a lack of an understanding of the short-term and long-term impact of these changes on the at-risk population. Thus, there is a need to bring together a more systematic approach with a Canadian perspective and adopt best practices from other countries and procedural disciplines. This rapid knowledge synthesis will bring together interdisciplinary teams from neurostimulation programs at three major hospital systems in Toronto who have been at the forefront of responsible delivery of their respective programs since the beginning of the COVID-19 pandemic. The project will be a collaborative effort with Infection Prevention & Control, Anesthesia, Nursing and Ethics across hospital systems. Importantly, the knowledge users will include leaders from academic hospitals across Ontario, pertinent stakeholders nationally & internationally and patients with lived experience. This project will offer a rational framework for decision makers at the hospital, provincial and other levels to offer neurostimulation treatments and mitigate the negative impact of COVID-19 on vulnerable populations. Further, it will form the foundation to develop services/targeted interventions, and delineate critical areas of knowledge gap in the procedural domain which need to addressed from an interdisciplinary perspective.",2020,2020,Unity Health Toronto Psychiatry,37461.75,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03153,"171712, 175517",Gender and intervention in dependency in the context of a pandemic with people in a situation of social insecurity,"file:///C:/Users/GrundH/Downloads/VFGID-COVID-IRSC-Synthseprliminairedesconnaissances_22.06.2020.pdf; Cette synthese de connaissance vise a guider l'amelioration des pratiques en dependance en contexte de pandemie, tenant compte d'une analyse basee sur le sexe et le genre relative aux divers besoins sociaux et de sante des personnes en situation de precarite sociale. Les personnes en situation de precarite sociale confrontees a une consommation problematique de substances font face a des risques accrus relativement a la COVID-19 comparativement a la population generale. Souvent aux prises avec des conditions de sante chroniques, ces personnes sont particulierement a risque de faire face a des consequences graves si elles deviennent infectees alors que les consignes sanitaires tendent a etre plus difficilement applicables a leur contexte de vie. L'experience d'une pandemie peut contribuer a declencher ou aggraver une crise psychosociale chez ces personnes deja confrontees a des troubles mentaux concomitants. L'OMS souligne que les consequences sociales de la COVID-19 frappe encore plus durement les femmes (precarite economique, monoparentalite, violence, barrieres a l'acces aux services, etc.). Un examen de portee ou scoping review permettra d'examiner les guides de meilleures pratiques et etudes evaluatives permettant d'identifier les interventions en dependance qui tiennent compte du genre pouvant etre recommandees pour les personnes en situation de precarite sociale en contexte de COVID-19. Aussi, environ 30 entrevues individuelles de 45 a 60 minutes seront menees aupres d'acteurs cles du Quebec possedant une expertise professionnelle ou un savoir experientiel sur le sujet d'etude (decideurs, praticiens et usagers de drogues). La synthese de connaissances permettra d'integrer les resultats de ces deux volets afin de guider la co-production de recommandations avec l'equipe de ce projet qui integre des chercheurs et des utilisateurs de connaissances provenant des milieux de la dependance et de la sante publique.",2020,2020,Université de Sherbrooke,74462.9,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C03154,171736,"Rapid evidence and gap map of virtual care solutions for youth and families to mitigate the impact of the COVID-19 pandemic on pain, mental health, and substance use","The COVID-19 pandemic is incredibly stressful, and will impact the mental and physical health of youth for the rest of their lives. Pain is one of the most common symptoms that youth experience when dealing with stressful events. Early information suggests that youth are experiencing more pain, like headaches and stomach aches, during the COVID-19 pandemic. This is important because pain contributes to worse mental health now and in the future. At least two million Canadian youth already have pain that lasts months to years (also called chronic pain). Youth who live with chronic pain are more likely than their peers to be anxious, depressed, have traumatic stress, and trouble sleeping. They are also more likely to continue to have pain, mental health problems, and misuse drugs as adults. We need to treat pain now to prevent lifelong issues for our youth. One of the major challenges of the COVID-19 pandemic is that many healthcare services are seeing fewer youth or have stopped treating them altogether. Overnight, it has become necessary to deliver medical and mental health care virtually (like using apps, websites, or therapy over video call). The goal of our project is to find out the best ways to delivery virtual care for youth who are dealing with pain and mental health concerns, and their families. We will find the answers by looking at the scientific research and by asking about any new ways healthcare services are being delivered virtually since the COVID-19 pandemic started. Our goal is to identify a range of virtual care options, including some that are good for all youth, and some that are best for youth needing more intensive mental and physical care. We will share this information widely in reports, on social media, and webinars so that the public, youth, families, healthcare providers, and government policymakers can make the best decisions to treat pain and prevent mental health problems in youth during the COVID-19 pandemic and in the future.",2020,2020,University of Calgary,37455,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03155,Supplement to P00168,Sex as a Biological Variable Supplement - Host Response Mediators in Coronavirus (COVID-19) Infection,"The coronavirus (COVID-19) epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. WHO and others are launching clinical trials of novel anti-virals. We have a unique opportunity to complement trials of anti-virals with investigation of modulation of the human host response to improve outcomes of COVID-19. We are proposing to ""repurpose"" a class of drugs (ARBs) for hypertension (high blood pressure) that have been shown to prevent lung injury in influenza and could work on corona because influenza and coronavirus bind to the same cell receptor in the lung. ARBs are commonly prescribed for high blood pressure (50-70% of patients). To date, there have been no clinical studies of ARBs in COVID-19. We call our study ARBs CORONA. We believe that ARBs can decrease the severity of COVID-19 and mortality of hospitalized COVID-19 infected adults. We will evaluate safety and effectiveness of available ARBs in COVID-19 in a multicentre study of 497 hospitalized adult patients who are or are not already on ARBs. Key personnel are in place to expedite this study. If this study is successful, ARBs can potentially limit complications and mortality of COVID-19. Potential results: ARBs are inexpensive clinically available cardiovascular drugs. If this study is successful, ARBs can potentially be used globally to limit complications and death due to COVID-19.",2020,2021,University of British Columbia,37449,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C03156,171732,Substance use among women in the context of the corollary pandemics of COVID-19 and Intimate Partner Violence (IPV),"With greater social isolation, stress and uncertainty during COVID-19, the risk of intimate partner violence (IPV) and substance use among women has increased. In Canada, there have been more IPV related calls, crises and shelter services have identified increased demands, and 10% of women have reported safety concerns. Substance use has also risen, with Canadians reporting more alcohol, cannabis and tobacco use during COVID-19 measures. In the proposed rapid review, we will examine how containment and pandemic related measures affects IPV and substance use among women, including level of consumption, types of substances used and changes in patterns of use. We will partner with three knowledge users representing first responders, shelters and substance use services, to co-develop evidence-based materials to support health care practitioners, IPV workers, substance use workers, and first responders in their work. We will apply sex, gender, equity, harm reduction and trauma informed lenses to analyze the literature and develop knowledge products. These materials will include information on IPV, substance use and COVID-related issues, guidance on responding to these issues, and suggestions for providing health advice and brief interventions.",2020,2020,"Centre of Excellence for Women's Health (Vancouver, BC)",37404.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C03157,171725,A rapid review of Opioid Substitution Therapy during major disruptions to medical care,"Background The recent months have seen a collision of two severe and complex health crises: the novel COVID-19 pandemic and the persistent epidemic of opioid related harms. Individuals living with opioid use disorder (OUD) are vulnerable to the pandemic and the changes it has caused. Opioid substitution therapy (OST) is first-line therapy for OUD and can be life-saving. It requires regular and frequent visits with health care providers, and thus has been affected by the requirements for physical distancing. Medication and drug supplies have also be disrupted during this pandemic. The risks of withdrawal, overdose, and diversion of opioids have increased so there is an urgent need to change existing ways to provide OST and support people with OUD. Research goals We aim to examine the perspectives and experience of opioid users and providers during times of disruptions to medical care. We also will look at how other OST programs have adapted during disruptions to care and alternative ways OST can be provided, such as virtual visits. Methods Because there is a lack of studies that examine the perspectives and experiences of people with OUD and providers of OST during COVID-19, we will do a rapid review of the literature on the impact of medical disruptions such as natural disasters or human conflicts on OST. Instead of launching a new search, we will instead use relevant data sets that we and our collaborators have already created for other reviews about OST. This non-traditional approach will improve the speed of the review and allow us to be more responsive to the pandemic. Impact We will work closely with government and health care decision makers from multiple provinces to apply lessons about how to change OST during and after the pandemic to better improve the health of people who use opioids. We will share our findings through multiple channels, including publishing in scientific journals.",2020,2020,Lunenfeld-Tanenbaum Research Institute (Toronto),37373.25,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03158,171702,Knowledge synthesis for mechanistic and targeted in-person and digital social-connection intervention for wellness and resilience in older adults in pandemic context and beyond,"Extended periods of social isolation and loneliness can have a negative impact on individual physical and mental well-being. This problem is particularly troubling for older adults as loneliness and isolation are risk factors for depression, heart disease, and premature death. Because they are also at greater risk of complications from COVID-19 infections, seniors have been especially targeted by social and physical distancing measures, further limiting their social interactions. In a post-lockdown world where social restrictions are likely to last for vulnerable aging populations, it is important to find the appropriate balance between physical distancing and social connection (be it in-person, digital, or a combination of both) to promote older adults' long term well-being and resilience. This project aims to answer the following questions: Among older adults, who are the most vulnerable to the mental health effects of social isolation? What strategies are the most likely to succeed in preventing or mitigating the effects of social isolation? To this end, we will review the most recent scientific evidence and share our findings with 'knowledge users' such as healthcare professionals, policymakers, and patient groups. Building upon these findings, we will be able to simulate different interventions using a digital platform known as SynthEco. This platform will assist decision-makers in evaluating the potential benefits and harms of the in-person and digital interventions identified by our project.",2020,2020,McGill University,37265.25,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C03159,171715,Supporting children and adolescents' mental health in the context of pandemic and confinement: A scoping review of interventions and ethical challenges,"During the COVID-19 pandemic, different measures are put in place to prevent the spread of the virus. Confinement and physical distancing measures are effective strategies to prevent contagion. However, these strategies can have a negative impact on the mental health of children and adolescents, with possibly worse outcomes for children and adolescents who had mental health issues before the pandemic. We will review the information available on the effect of pandemics on the mental health of children and adolescents to identify ways to better support them and their families. We will also identify the ethical challenges that can be present for these families in the context of a pandemic and offer ways to address them. We will summarize the information available and share the results within one month after the start of the project. We will then update the results based on additional information available in the following months. Our goal is to provide concrete ways to better support children and adolescents' mental health needs and their families.",2020,2020,McGill University,37221,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Indirect health impacts,2020 +C03160,171713,Pandemic-Proof: Synthesizing Real-World Knowledge of Promising Mental Health and Substance Use Practices for Young People Who Are Experiencing or Have Experienced Homelessness,"An estimated 35,000-40,000 Canadian youth (aged 13 - 24 years) experience homelessness at some point during the year and at least 6,000 on any given night. Most of these young people have experienced some form of trauma and really struggle with challenges around mental health and substance use. We also know that young people continue to struggle once they leave homelessness; many continue to live in poverty and feel very isolated and lonely. COVID-19 has highlighted that this pandemic is negatively impacting some more than others. This is particularly true for the young people we serve. Many have lost jobs, do not feel safe where they are isolating, or feel a bit lost without any day-to-day structure. At the same time, physical distancing measures mean most places providing mental health and substance use supports are closed. Still, despite these challenges, we are hearing from our colleagues on the front lines that some are trying really innovative things to connect with young people who have experienced or are experiencing homelessness. In fact, we believe that some of these ideas may be really forward thinking and should continue after the pandemic is over. We want to do three things: 1) Send out an electronic survey to folks across Canada working with young people who are experiencing or have experienced homelessness to understand how they have adapted their practices. 2) Do a ""deeper dive"" and interview those who are doing particularly innovative things to understand what seems to be working well and for whom (e.g., youth who identify as female vs. youth who identify as male). 3) Share this information quickly with folks on the front lines and in government in a way that is easy to understand and helps them make informed decisions.",2020,2020,McMaster University Nursing,37161,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03161,171746,Palliative Care for People who use Substances During Communicable Disease Epidemics and Pandemics: A Scoping Review,"The COVID-19 pandemic and its response efforts magnify the health care challenges encountered by people who use substances. People who use substances are at high risk of life-limiting illnesses such as end-stage organ failure and cancer. Unfortunately, people who use substances encounter barriers to receiving palliative care. People who use substances often have few social supports and lack financial resources. Moreover, delivery of community-based health services may be restricted due to institution and provider concerns that the settings are risky or unsafe. Zero-tolerance policies toward non-medical use of substances also restrict access to palliative care units and hospices. Given these pre-existing inequities to palliative care access and increased demand for palliative care during the COVID-19 pandemic, it is important to understand the impact of COVID-19 on people with life-limiting illnesses who use substances. To address this critical issue, we propose a scoping review that will identify knowledge strengths and gaps about palliative care for people with life-limiting illnesses who use substances during communicable disease epidemics and pandemics. Our project will critically assess the state of knowledge and provide decision support for healthcare providers and policy makers during COVID-19 and future communicable disease epidemics and pandemics. Through our dedicated knowledge translation strategy, we will ensure timely dissemination of our findings to patients, caregivers, healthcare providers, and decision makers. Our project is aligned with a key goal in the Government of Canada's five-year action plan for palliative care (2019 - 2024), which seeks to to improve access to palliative care for underserved populations who experience difficulties in obtaining health care and to improve the quality of care when it is received.",2020,2020,Princess Margaret Cancer Centre (Toronto),37125,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C03162,171704,Knowledge Synthesis to Support and Promote Mental Wellness and Resiliency during the COVID-19 pandemic,"There are currently no vaccine or cures for COVID-19. As a result, our government recommends isolation, quarantine, and other measures to control the virus. However, when people isolate for a long time, their mental health may suffer. Some people with no mental illness, for example, may develop anxiety or depression, with symptoms that can last a long time. Others who are already living with mental illness may experience worsening symptoms, and at the same time experience difficulties accessing their usual health care or social supports. It is therefore important to support the mental health of the population during a pandemic. In line with this, our team of researchers, mental health professionals, and people with lived experience, propose to conduct a rapid review of the evidence on home activities and resources that can support mental health during times of isolation. We also propose to conduct an online survey to understand what activities or resources people prefer and will most likely use. Upon completion, study results will be shared with the government, CMHA and the CIHR. We will create a public website to share the results, with selected examples of effective home activities or resources. A research paper will also be submitted for publication. The results of our study will complement government plans to address the mental health impacts of COVID-19. It will work well, for instance, with the virtual mental health platforms that the government is planning to fund with $240M. We plan to update the project website with new evidence and examples from the literature as they become available so that the website continues to be a useful resource even long after the pandemic is over.",2020,2020,University of British Columbia School of Population and Public Health,36088.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03163,171731,Alcohol consumption and the COVID-19 pandemic: synthesizing knowledge for policy action,"Health researchers are warning that alcohol use and alcohol dependence in many jurisdictions may be increasing due to the COVID-19 pandemic; however, scientific evidence is sparse on the impact of the pandemic on alcohol consumption and alcohol-related harms (e.g., violence against women and children). Thus, a comprehensive understanding of the impact of COVID-19 on short-term and long-term alcohol use and related health harms is urgently needed to inform policy and practice. The proposed project will result in the rapid (within one month of project commencement) production of evidence-informed guidelines for alcohol control policy recommendations. Guidelines will be updated monthly as more information is synthesized by the research team. The guidelines will be based on the following three unique research projects: 1. A systematic scoping review which will a) assess the current state of knowledge regarding how similar crises (e.g., economic crises and natural disasters) affect alcohol consumption and resulting health harms, and b) assess the applicability and/or transferability of these data to the current pandemic context. 2. An analysis of existing data sources, including general population survey data and alcohol sales data, to examine changes in alcohol consumption in Canada since the start of the COVID-19 pandemic. 3. Individual and group interviews with a diverse set of experts to synthesize knowledge from multiple disciplines and to reach consensus on a) the expected short- and long-term impact of the current pandemic on alcohol consumption and related health harms, and b) policy actions required to minimize the negative health effects from increased alcohol consumption during the current pandemic and future crises. The results will inform and assist policy makers in determining which alcohol policies should be implemented during the current pandemic and future crises to mitigate alcohol-related harms.",2020,2020,Centre for Addiction and Mental Health (Toronto),35843.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2020 +C03164,171724,"Translating Knowledge for Child Welfare Organizations Across the Prairies: Managing the Impacts of COVID-19 on the Mental Health of Children, Families, and Workers","The shifting circumstances surrounding COVID-19 have led to a rapid proliferation of research and resources, but organizations responsible for meeting the urgent needs of children and families in child welfare typically have little time to find, evaluate, and translate knowledge to inform services for vulnerable children and families. The conditions brought on by COVID-19 have increased the possibility of separation, isolation, and reduced social support, as well as education, mental health, and physical health services. Thus, children and families are at heightened risk for trauma reactivation and deteriorating family conditions. Workers are also challenged in their efforts to rapidly change practices to respond to increasing demands and the growing complexity of cases, to ensure the safety and well-being of children and families. Thus, in close consultation with existing and new partners, we will undertake a rapid, month-long knowledge scan, synthesis, and subsequent mobilization initiative related to child welfare and COVID-19, geared to child-serving organizations from across the Canadian Prairies. We will use a variety of mobilization outlets, including an innovative Digital Connections Hub, which will be organized into policy, systems, and best practice responses to meet the mental, physical, and social health needs of children, families and workers. We will focus on the unique needs of Indigenous peoples, females, and others at risk of the compounding effects of COVID-19 on existing inequalities. Through an established infrastructure, affiliation with several research centres, and a well-connected research team, our initiative will contribute significant benefits by providing a forum for access to synthesized, vetted research and accessible resources to increase knowledge and support for child and family services providers. This will in turn improve the physical and mental health and well-being of vulnerable children and families during COVID-19, and beyond.",2020,2020,University of Regina (Saskatchewan),35506.5,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Indigenous People | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03165,171709,Mental health and substance use among children and adolescents amidst COVID-19- A Systematic Review,"The coronavirus disease 2019 (COVID-19) pandemic and the social distancing measures that have been implemented worldwide have caused disruptions to the daily routines of people. Children and adolescents are generally healthy and do not require much health care outside of regular checkups. However, mental health care is very important for children and adolescents. The COVID-19 pandemic may worsen existing mental health problems among children and adolescents and may lead to harmful consequences such as substance abuse. Organizations such as UNICEF and WHO have developed some tools and initiated phone lines to improve the mental health of young children during COVID-19. The Centre for Addiction and Mental Health (CAMH) and the Centers for Disease Control and Prevention (CDC) have also recommended several strategies to maintain the mental wellness of young children and adolescents during the COVID-19 pandemic. However, not much is known about the long-term mental health effects of large-scale disease outbreaks on children and adolescents. Therefore, it is important to monitor the impact on children's and adolescent's mental health and substance use status and how to help them to improve their mental health outcomes in the time of current or future pandemic. The aim of this knowledge synthesis study is to identify and evaluate the effectiveness of different interventions employed during the previous and current pandemic to promote children's and adolescent's mental health and to prevent substance use.",2020,2020,University of Alberta,35164.5,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03166,171739,COVID-19 pandemic guidelines for mental health support of racialized women at risk of gender-based violence,"Gender-based violence (GBV) affects 30-60% of women, impacting their mental, physical, and sexual health. Violence against women contributes to high levels of morbidity and mortality. It is associated with life-long mental health impacts including anxiety disorders, depression, and substance use disorders. Studies report higher rates of past suicide attempts and social exclusion and isolation. Global statistics reveal a drastic increase in violence against women during the COVID-19 pandemic. Fear, uncertainties and stressors among the population during the pandemic contribute to anger and aggression against spouses and partners. Worldwide warnings (including Canada) are raised on the increasing domestic violence during the crisis. Growing evidence also shows that racialized groups are especially at higher risk of COVID-19 related morbidity and mortality. Our project's overall goal is to advance trauma-informed mental health care for racialized women at risk of GBV during the COVID-19 pandemic response and recovery phases. We will conduct a rapid review to assess the state of knowledge on mental health among women exposed to GBV during the COVID-19 pandemic, and to identify best practices for detection, referral, and service provision for mental health promotion and care. We will adapt the Cochrane Rapid Reviews method, and will be guided by an equity lens in conducting rapid reviews on public health issues. We will engage in gender-specific knowledge exchange with different sectors. Our project's outcomes will be: a Rapid Review of synthesised findings, an Information Brief, an Infographic, and a Toolkit. We will also prepare a Peer-review Article and a Policy brief. Finally, we will develop emerging Guidelines to assist racialized women at risk of GBV and service providers on mental health supports during the COVID-19 pandemic in Canada.",2020,2020,York University,34927.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03167,171708,School-Based Suicide Risk Assessment Using eHealth: A Scoping Review,"Suicide is the second leading cause of death for Canadian youth. In the context of COVID-19, suicide risk among youth is likely further elevated due to social isolation and associated mental health impacts. Thus, this project will explore school-based suicide risk assessment with youth via eHealth in the context of COVID-19. Given their frequent access to and relationships with most youth, schools play a key role in suicide prevention. For example, school personnel can provide suicide risk assessments so that students can be appropriately referred to community-based intervention. However, training for school personnel on how to assess for risk in an effective, standardized way is lacking. In response, a multi-sectoral team in Alberta developed a School-Based Suicidal Ideation Response Protocol (the SI Protocol), which provides standardized response patterns for school personnel. The protocol is now implemented in over 100 schools in 3 divisions, and preliminary evaluation data suggest that the protocol increases sensitivity and specificity of response, and increases school personnel comfort and preparedness to assess for suicidal ideation. However, because schools across the province are now closed due to COVID-19, school personnel need to connect with students - and implement the SI Protocol - using remote technologies. As a result, our school partners have expressed a need for timely information on how to e-deliver the SI Protocol. To fill this evidence gap, this project will use a systematic scoping review to explore promising practices for conducting school-based suicide risk assessment with youth via eHealth. This proposal will address a critical gap in the provision of targeted intervention to support the mental health of youth in the context of COVID-19. As remote delivery is also likely needed in many other jurisdictions globally, findings from this review have the potential for broad impact on school-based mental health service delivery.",2020,2020,University of Calgary Psychology,32830.5,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03168,Supplement to P00182,Sex as a Biological Variable Supplement - Drug repurposing for the rapid development and evaluation of SARS-CoV-2 antivirals,"The initial symptoms of COVID-19 are fever, shortness of breath and a dry cough. For some patients, the disease progresses to pneumonia as the infection spreads to the lung and leads severe inflammation. These severe symptoms can cause difficulties for the lungs to oxygenate the blood and can lead to death. There are currently no antivirals against SARS-CoV2, the causative agent of COVID-19, and development of new molecules can take years to reach patients. As the COVID-19 epidemic is progressing rapidly, the need for antiviral therapy is urgent. Therefore, our goal is to use our current arsenal of approved drugs already tested for their safety and used in the clinic for various conditions and repurpose them to treat COVID-19. In this rapid response grant, we propose to identify drugs with activity against SARS-CoV2 in vitro and in vivo and contribute to the global COVID-19 response and provide a therapeutic option for patients developing life-threatening disease.",2020,2021,University of Ottawa,30000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03169,171727,Pandemic experiences and impacts of COVID-19 on the mental health of Indigenous communities,"This Study responds to the call for practices and platforms to inform population level responses to COVID-19 generated Mental Health and Substance Use (MHSU) concerns for Indigenous peoples living in BC. It's designed in response to our objective to contextualize the current evidence base on MHSU service needs, delivery, and related guidelines, practices and issues within the COVID-19 pandemic so as to provide decision makers with high quality, timely, accessible, and relevant evidence in a short period of time. Our research approach is shaped by leadership in our collaboration with the Nisga'a Nation, and with an Indigenous Communications and Web design professional practiced in Indigenous Community Based Knowledge Translation methods. The populations we are seeking to address are Indigenous peoples living in BC in the COVID-19 context more generally, and more specifically, Indigenous peoples living in more remote regions of the Pacific Northwest Coast. Our broad knowledge synthesis (KS) approaches include literature searches, social and health policy analyses. Our case specific approach with the Nisga'a Nation permits our KS to address the unique MHSU COVID-19 concerns to Indigenous peoples in Northern BC. This study will also examine the gendered impacts of COVID-19 on the MHSU of Indigenous women. The outbreak of COVID-19 amplifies existing inequalities for Indigenous women who occupy vulnerable social positions including income, housing, and food insecurities. This study will contribute to the establishment of a gendered lens and analytical framework on the gendered impacts of COVID-19 on the MHSU in Indigenous communities.",2020,2020,Simon Fraser University,27159,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2020 +C03170,171737,The Impact of COVID-19 on the Mental Health and Well-being of Caregivers and Families Living with Autism,"Caregivers and families (i.e. siblings) with children and adolescents with autism often experience demanding stressors and distress associated with providing care to the family member with autism. We aim to better understand what has been documented regarding the impact of the COVID-19 pandemic on caregiver and family functioning and identify the supportive programs that have emerged as a result. Before COVID-19, the literature has shown that caregivers of people with autism experience more stressors, more mental health problems and distress, and lower family quality of life, compared to the general population. As a result of the state of emergency due to COVID-19, these stressors and mental health outcomes have likely increased. Distancing requirements have halted many of the programs that caregivers rely on for respite and support (e.g. interventions, day programs, schools, adapted recreation and leisure, etc.). This means caregivers have little or no assistance outside of the family to care for their child with autism. It is essential to recognize the service needs of families, and share the evidence-based best practices that have emerged to support caregivers of children with autism who are faced with these pandemic-related demands. Using a comprehensive family coping model (called the Family Adjustment and Accommodation Resource Model) as a framework, the proposed rapid knowledge synthesis review will outline how families balance the many demands they experience with the services and resources that support their capabilities, and how they make meaning of this process as a means of coping. Moving forward, addressing the mental health of caregivers is an essential part of supporting the wellness of children. By quickly finding and sharing what works to support the mental health of caregivers and families during COVID-19, we can stop and reverse the increasing tide of mental health problems and distress that is emerging in the Canadian autism community.",2020,2020,York University (Psychology),25551,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03171,Supplement to P00052,Sex as a Biological Variable Supplement - Rapid Response to Emerging Serious Pathogen Outbreaks using Next-gen Data: R2ESPOND,"A new virus has been identified from Wuhan City in China from the coronavirus family (SARS-CoV-2), which is now responsible for more than 71,000 cases of illness (COVID-19 disease) in over 29 countries. Although there have not yet been any deaths in Canada, public health agencies are on high alert, as there is a real possibility of a serious epidemic. The WHO has declared COVID- 19 a public health emergency of international concern. As of February 14th, five COVID-19 cases have been confirmed in British Columbia and based on travel patterns there is every reason to expect additional cases in BC. There are many unanswered questions regarding the virus, how it spreads and the disease that it causes. This information is needed for a data-driven response to this outbreak. We aim to use two types of next-generation data (next-gen genomics data and next-gen human data), along with a data integration tool called PLOVER 2.0, to answer these unknowns. The research team will 1)Carry out rapid genomic sequencing on patient samples to study the virus, how it spreads, how it evolves and predict which drugs will work 2)Develop knowledge of how the virus characteristics, along with a patient's previous health conditions, impact the severity of illness and how they recover from the illness 3)Develop a software tool (PLOVER 2.0) that will allow us to carry out this research and will also make the data viewable by key stakeholders such as Medical Health Officers. This work will not only generate critical knowledge about the SARS-CoV-2 virus but will also help develop a better understanding of health outcomes for infected patients. The knowledge generated and tools developed by this research can ensure an evidence-based and cohesive response to this public health emergency, here in Canada and internationally.",2020,2021,University of British Columbia,18750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2020 +C03600,unknown,Blood test to predict the severity of COVID19,,2020,-99,AGE LABS AS,660330,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Clinical characterisation and management,Prognostic factors for disease severity, +C03601,unknown,Introduction of clinically tested digital integrated follow-up of outpatient patients during and after pandemic,,2020,-99,DIGNIO AS,866580,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,Innovation,,,Norway,Norway,Clinical characterisation and management,"Supportive care, processes of care and management", +C03602,unknown,Development of a novel high-throughput COVID-19 antibody test,,2020,-99,GENTIAN AS,880000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C03603,unknown,Interaction applications in the health service for crises and day-to-day operations,,2020,-99,IMATIS AS,596640,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,Digital Health,,,Norway,Norway,Clinical characterisation and management,"Supportive care, processes of care and management", +C03604,unknown,An artificial intelligence platform to identify T cell targets for rapid response tests during pandemics: application to SARS-CoV-2,,2020,-99,NEC ONCOIMMUNITY AS,852390,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C03605,unknown,Easy and safe contact with relatives,,2020,-99,NO ISOLATION AS,443080,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Infection prevention and control,, +C03606,unknown,Development of antibody-based technology for the treatment of COVID-19-infection,,2020,-99,NORIMUN AS,440000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Therapeutics research, development and implementation",Pre-clinical studies, +C03607,unknown,Systemic Pandemic Risk Management,,2020,-99,STEPCHANGE AS,880000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,,, +C03608,unknown,COV- best practice for video solutions and digital supervision in health services,,2020,-99,TELLU IOT AS,465520,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,Innovation,,,Norway,Norway,Clinical characterisation and management,"Supportive care, processes of care and management", +C03609,unknown,Defining the immune cells that correlate with fatal acute lung injury in COVID-19 and in two clinical trials for severe disease,"The ongoing COVID-19 pandemic requires information that could stratify patient treatment and new treatment options for the minority that develop fatal lung injury of unclear pathogenesis. Very few studies have focused on defining SARS-CoV-2 viral interaction with the host immune system, natural history and the pathogenesis of severe disease. This project is designed to discover important pathogenesis principles that may guide triage and choice of therapy, allow an understanding if immune inhibition should play a role, facilitate two clinical trials and suggest novel biomarkers that can point to patients that risk developing life threatening lung disease. We propose a multidisciplinary groundbreaking study of material from blood and bronchoalveolar space from lungs of COVID-19 patients that develop acute fatal lung injury. We will define the pathogenic disease course and biomarkers of fatal disease with single cell mass cytometry and RNA sequencing. Cells from two international clinical trial launched in accordance with the ""Proposed next steps"" in the 2020 WHO Roadmap will be compared for inflammatory signature. We ask what exact types and subsets of inflammatory cells that secrete pro-inflammatory cytokines, a cytokine storm and inflammation that destroys lung tissue. We ask if there is too weak or too strong immune responses in fatal COVID-19. We ask if convalescent patient serum with neutralizing antibodies can reduce the inflammatory cells that cause lung injury. We also ask if cell therapy with immune inhibitory decidua stroma cells (DSC) can negate the cellular inflammatory responses and fatal lung injury in COVID-19. Results will suggest new biomarkers for risk stratification, and triage, test the effect of convalescent serum and immune inhibitory DSC, have importance for the use of cheap anti-inflammatory medication in low-income countries, and will be disseminated in a European lab network to allow improved laboratory prediction of severe lung disease.",2020,2021,OSLO UNIVERSITETSSYKEHUS HF,353870,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C03610,312707,"EU-COVID-19 - a multinational registry-based linkage study with focus on risk and protective factors, clinical outcomes and mental health.","Background and aim: The background for this multinational project is the urgent knowledge gaps on epidemiological factors and consequences of COVID-19 in the general population and vulnerable groups. Moreover, understanding whether available pharmacotherapy options may modify the course and severity of COVID-19 infection, and the impact of the COVID-19 threat on mental health, is an impelling clinical question. The proposed project aims to fill these gaps by generating timely, methodologically sound evidence stemming from high-quality, detailed, and already available population-based data covering a population of over 30 million inhabitants. Methods and material: The project capitalizes on our access to high quality registry data in four countries, Norway, Italy, Denmark and UK, representing individual level patient data across countries with different incidences of COVID-19, and covering different types of health care systems. Design: Register-linkage cohort study with cross-sectional and longitudinal analysis to examine time trends (2018 - 2020). Results will be incorporated in an innovative online risk predicting tool that can be used to predict individual-specific risk for severe COVID-19 infection and prognosis, which is applicable in clinical setting. The research team is highly interdisciplinary, with expertise spanning from the field of epidemiology to pharmacology, biostatistics (incl. machine learning techniques for risk prediction), paediatrics, infectious diseases, signal detection and regulatory pharmacovigilance. The project is a two-year project starting 1. July 2020 and ending 30. June 2022.",2020,2022,UNIVERSITETET I OSLO,546700,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway | Italy | Denmark | United Kingdom,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures","Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Indirect health impacts",2020 +C03611,unknown,"Norwegian SARS-CoV-2 study - Virological, clinical and immunological characterisation of inpatients during the COVID-19 outbreak","The Norwegian SARS-CoV-2 study is designed as a multicenter hospital based cohort study that will allow us to analyse the disease outcome in relation to risk factors and intervention in a large material across institutions. All health regions in Norway are represented in this research initiative to minimise any bias in the material. To address the pathogenicity, we will investigate patients at different time points from inclusion in the cohort according to the ISARIC protocol to assess different outcomes by serial sampling and clinical data collection. We will use rapid syndrome-based point-of-care testing, Whole Genome Sequencing and Next Generation Sequencing to detect co-infections and for detailed studies of virological causes of severe outcome. Such novel sequencing techniques will be employed in collaboration with virologists at Wuhan Institute of Virology, Hubei, China, allowing for comparison with strains from the origin and start of the SARS-CoV-2 pandemic. The study will generate much needed knowledge on the clinical features of the infection, longterm morbidity and mortality and occurrence of co-infections and will describe the response to treatment, including supportive care and novel therapeutics. We will observe pathogen replication, excretion and evolution, within the host in various biological material. Further, we aim to investigate host immune responses over time during hospitalisation and at follow-up in relation to clinical outcome. This large study provides an excellent framework for a PhD fellowship focusing on the pathogenicity of SARS-CoV-2, co-infections and the study of virus mutations and dissemination in the patient over time and across cases using novel virological techniques. Furthermore, data on the whole genome of SARS-CoV-2 from our study will be compared with cases from Wuhan, the origin of the outbreak. The data will be shared with the international scientific community through the Oxford Database solution REDCap.",2020,2022,UNIVERSITETET I OSLO,548240,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe | Western Pacific,,,,Norway,Norway | China,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease susceptibility | Disease pathogenesis",2020 +C03612,unknown,Survival rates and long-term outcomes for patients with COVID-19 admitted to Norwegian ICUs,"The study will be conducted as a collaborative study between Norwegian Intensive Care Register (NIR) and Oslo University Hospital. The study will explore and describe the Norwegian ICU-population with COVID-19. NIR is one of several national quality registries in the Norwegian health care system. Registration is mandatory for all ICU-admissions fulfilling specific criteria. This will increase the generalizability of the results. The data collected during the COVID-19 epidemic may also be compared to existing NIR data, particularly those obtained from previously registered influenza patients, to identify similarities and discrepancies in the management and outcomes in these groups of patients. Respiratory failure is the main cause of ICU-admission for COVID-19 patients. The present project will also collect follow-up data from the NIR registry for all survivors of COVID-19. The negative consequences of surviving an ICU stay has received increased attention in recent years, as decreased mortality rates have contributed to a high number of ICU survivors. It has been reported that survivors of ARF of any aetiology report substantial impairment in physical functioning and quality of life (QOL) up to 5 years after ICU discharge. The one-year follow-up study will include questionnaires that captures physical, psychological and mental health related challenges occurring after ICU treatment.",2020,2022,Oslo Universitetssykehus,431860,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C03613,unknown,COVID-19 Public Response and Rapid-Cycle Re-Implementation of Activities,"This project aims at disentangling the following two overarching and important questions related to the current COVID -19 pandemic: 1. What are the implications of the decisions by authorities in Norway during the COVID-19 pandemic in Norway 2. How can we rapidly and safely re-open important public activities without increasing risk of disease? Working packages 1 will answer question 1 by: • Real-time analysis of the events as they are unfolding by feeling the pulse of the population through group interviews and questionnaires during the outbreak to understand fears, trust, and opinions. • Estimate effects of these measures on health outcomes in the population by linkage to Norwegian registries after the outbreak Working packages 2 will answer question 2 by: • Rapid-cycle randomized testing of re-opening training facilities at Studentsamskipnaden i Oslo with close monitoring of disease activity. We will find the safest and fasted way to relieve society from the burden of restrictive COVID-19 measures. Our aim is to provide the public and decision makers with high-quality, evidence-based real-time advice on the most crucial decisions they will need to make during and after the COVID-19 outbreak.",2020,2022,UNIVERSITETET I OSLO,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Epidemiological studies | Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Governance | Approaches to public health interventions | Policy research and interventions | Social impacts,2020 +C03614,unknown,Monitoring the actual population prevalence of SARS-CoV-2 infection in Norway to model and predict the current and future epidemic,"The current COVID-19 pandemic is an emergency with difficult challenges. Most cases have mild symptoms and transmissions occur pre-symptomatically or even asymptomatically. Furthermore, there are large differences in mortality rates between countries. Limited testing and epidemiological uncertainties lead to possible underestimation of the scope of the epidemic. Data are urgently needed to estimate the true prevalence of the disease and tools to assess changes and predictions of the epidemic dynamics. The goals of this project are to assess the point prevalence the Sars-Cov-2 virus in the Norwegian population, to accurately model the epidemic dynamics and establish a system for continuous assessment of changes in prevalence, incidence and overall immunity in the population. Point prevalence will be assessed by collecting sputum samples in a random sample of 4000 Norwegians above the age of 5. This will be repeated after two months on a new set of individuals. Sampling kits are delivered directly to each participant by Bring, collected the day after and shipped to the laboratory for analysis. Additionally, the participants will complete a questionnaire with personal information, including living/working conditions and travels. The participants will report symptoms on a weekly basis through the NIPH platform hosted by Helsenorge. Additional sputum/swab samples may be collected, depending on necessity and funding availability. Later all participants will be asked to donate a blood sample through their Home Doctor Network (Praksisnett) to assess overall population immunity. Questionnaires and transportation databases will allow machine- and complex network modeling to improve understanding of the evolution of the epidemic. Comparative data analysis will be carried out in collaboration with our international partners (UK and Italy. The project will be part of a national effort and an open source dashboard will be implemented to make data and results available.",2020,2022,UNIVERSITETET I TROMSØ - NORGES ARKTISKE UNIVERSITET,550000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway | United Kingdom | Italy,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease surveillance & mapping,2020 +C03615,unknown,"COVID-19 Seasonality: The effect of environmental variation on the spatio-temporal dynamics at national, regional and global scales","COVID-19 Seasonality is a Norwegian based project with strong collaborations with leading research and response organisations in China, Iran, UK, USA, and the African Union to develop fundamental information and inform the response to the ongoing COVID-19 pandemic. The objectives are organized into three Work Packages (WP) to (I) Extract the functional response of SARS-CoV-2 to environmental factors (including weather/seasonal variation) from variations in the growth rate of the COVID-19 pandemic; to (II) Predict the near term and long term seasonality and age-specific burden of infection of COVID-19 in Norway and other countries; and to (III) Prepare Norway (and other countries) for future pandemics by assessing the potential speed and intensity with which new emerging infectious diseases (EIDs) will arrive from geographic high-risk regions. Early in the project, we will produce quantitative models to forecast the seasonal conditions in Norway and other countries that favour and hinder the transmission of SARS-CoV-2, improving predictions of epidemic trends. We will continue to improve and iterate on these models throughout the project. In addition to the quantitative models, we will produce three high-quality novel datasets: (1) a dataset of the timing and spatial extent of various control measures, testing regimes and hospital patient overflows, (2) a dataset of global hotspots of human-wildlife interactions sourced from grey and published literature, and (3) a spatial database with a probabilistic assessment of the speed and intensity with which future viral spillovers are expected to arrive. We will through COVID-19 Seasonality carry out basic research and apply the obtained insights to one of the biggest challenges of our time. We expect that improved understanding of the spatio-temporal dynamics of COVID-19 pandemic will contribute profoundly to improve the preparedness against future diseases in Norway as well as globally.",2020,2022,UNIVERSITETET I OSLO,550000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Americas | Eastern Mediterranean | Europe | Western Pacific,,,,Norway,Norway | China | Iran | United Kingdom | United States of America,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities,2020 +C03616,unknown,COVIDOSE: Determining infectious dose for SARS-CoV-2 and assessing contact/proximity risk,"The COVIDOSE project has a goal-oriented and straightforward approach to its first and main goal: determining the infectious dose, i.e. the minimum number of SARS-CoV-2 virus particles needed to start an infection resulting in disease, achieved through coalescent analysis on population-based viral genomics sampled from Norwegian patients. Furthermore, this will be compared to samples from likely contact points in the environment to contribute to risk assessment and transmission dynamics. Lastly, an innovative outreach plan enables an open platform for our research. It draws on a small, dedicated team of specialists well placed for such a study. The team consists of highly creative,ambitious and talented researchers in established yet highly productive career stages with the ability, experience and drive to accomplish our objectives. Our work is highly visible and has been featured in Nature, Science, PNAS, Nature Communications, Nature Ecology & Evolution, among other top journals.",2020,2022,UNIVERSITETET I OSLO,471240,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Epidemiological studies,Disease transmission dynamics,2020 +C03617,unknown,Stress responses and health complaints in hospital personnel during the Covid-19 pandemic,"Background The COVID-19 pandemic is currently spreading rapidly, and critically ill patients are increasingly admitted to hospitals, putting a heavy toll on already highly pressured healthcare systems worldwide. In response to the crisis, there is an urgent need to identify measures to adequately support critical personnel`s efforts and safeguard their physical and psychological health and well-being. Objective This study aims to map Covid-19 related work strain factors and critical incidents and investigate the potential impact on levels of distress and health condition during the outbreak. During the critical phases of the outbreak the study will identify risk factors for distress and health complaints and suggest measures needed to be implemented to reduce their impact. Methods The study recruits health care personnel involved in treatment of hospitalized patients infected of Covid-19 in different hospital units in four regional university hospital in Norway. Participants report on Covid-19 work strain and critical incidents at work, individual and work place related factors, work schedules, levels of psychological distress and health complaints including headache, musculoskeletal pain, sleep problems and burn-out. Sensors measuring activity and rest compliment self-reported data of sleep and rest. In analyses of the data we will apply a mixed methods approach, using qualitative and quantitative data. Participation in the study is based on informed written consent and measures will be taken to protect privacy and ensure voluntary participation. Results This study will provide urgently needed knowledge on how the Covid-19 outbreak impact health care personnel`s work load during the phases of the pandemic and provide critical information to stake holders on risk factors needed to be addressed to reduce work-related stress.",2020,2022,NASJONALT KUNNSKAPSSENTER OM VOLD OG TRAUMATISK STRESS AS,546260,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03618,unknown,Digital Infrastructure for Robust and Scalable Patient Monitoring in Pandemic Response Situations,"A digital solution for home-monitoring of patients with suspected COVID-19 has been operational since March 19th in the region of Agder. Patients' self-reporting of symptoms are transferred to clinicians who follow up the progression of the disease. This is made possible by leveraging the existing platform for digital home monitoring of patients with chronic diseases. However, the situation of a pandemic poses certain novel demands to the solution. Our overall research question (""which novel capabilities are required when designing home-monitoring services for forward triaging and remote care in a pandemic usage situation?"") will be answered through both evaluative and exploratory research. A systematic evaluation of the current home monitoring solutions and services will be conducted in order to provide quality assurance and identify areas for improvement. A digitally integrated service across the organizational levels will be designed. Further, digital home monitoring allows systematic capture of unique, patient-reported, early-phase disease data. We propose to systematically capture these data for both short-term optimization of the response to the pandemic, to create a data resource for research oriented towards knowledge building, e.g. on long-term health outcomes. This unique data source will also be a crucial resource for the project's further ambitions: to explore the possibility to strengthen monitoring with e.g. predictive models, assistive intelligence and AI-enabled automation. We will explore the potential for innovation and improvement of the underlying ICT platform, to be able to accommodate third-party solutions and for the platform to be scalable and flexible. Such third-party solutions are e.g. new data sources (from other monitoring technologies such as IoT devices and wearables), and solutions that support analysis. The potential for AI-assisted monitoring and diagnostic tasks will be explored in co-operation with the industry.",2020,2022,University of Agder,546260,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,Digital Health | Innovation,,,Norway,Norway,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health service delivery",2020 +C03619,unknown,CovidNor - Experiences of patients and primary health care professionals during the COVID-19 epidemic in Norway,"Current research on the clinical manifestations of COVID-19 have been mainly based on hospitalized patients. However, most infections are not severe and a majority of COVID-19 patients are diagnosed and handled in primary care. The overall project objective is to understand the clinical picture of early, mild to moderate forms of the disease and fears and experience of safeguarding among people personally affected by COVID-19 outside hospitals, as well as the response of the local medical teams in primary health care and the supporting health care system response including infection prevention and control. Through a web-based survey, we will invite people in isolation/quarantine at home to report symptoms and personal experiences and emotions throughout the course of the illness and/or period in isolation/quarantine. The survey results will be linked to registry follow-up to detect complications and long-term effects of COVID-19. We will invite general practitioners (GPs) to record case information of patients with respiratory tract infections during six weeks of the epidemic to provide clinical information of patients presenting to primary care. In-depth interview studies from a primary care perspective of GPs, leaders of municipal out-of-hours units and municipality chief medical officers will provide insight into how health care workers in Norwegian and Swedish primary care handle the epidemic. We want to focus in particular on their experiences of the local health care system responses including infection control. The clinical observational data of cases outside hospitals, both self-reported data and reported by GPs, will provide knowledge of the natural history of mild to moderate COVID-19 cases. This may help clinicians and health authorities in better identifying patients with COVID-19. The interview studies will provide valuable information regarding the infection control response during the epidemic as experienced from primary care and municipalities.",2020,2022,Institutt for helse og samfunn,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway | Sweden,"Clinical characterisation and management | Infection prevention and control | Secondary impacts of disease, response & control measures | Health Systems Research","Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Barriers, PPE, environmental, animal and vector control measures | Indirect health impacts | Health service delivery",2020 +C03620,unknown,Drivers of public responses toward Coronavirus outbreak and implications of social dynamics (COSD),"As humanity is facing for the first time in contemporary history, a pandemic with such impactful and unpredictable effects, understanding the drivers of public responses toward the Coronavirus outbreak is essential. Emerging research in the areas of the public's reactions toward similar epidemics (the Ebola crisis and the SARS epidemic) has been piecemeal. This project aim to apply a more holistic approach to investigate public responses toward the pandemic and actions taken by authorities, individuals and businesses. We develop and test an integrative social psychological theory that combines specific emotional, cognitive, evaluative, and individual difference variables that undergird the public's reactions to social countermeasures taken to the outbreak of coronavirus. The project is organized in two working packages. WP1 studies public responses toward the outbreak of coronavirus and social countermeasures broadly through a longitudinal survey in Norway, which will exam naturally occurring relationships amongst psychological reactions over time to ascertain the direction of causality. WP2 examines the socio-psychological mechanism underlying public responses toward countermeasures taken by authorities, individuals, and business. Field experiment with adult respondents will be conducted across 4 countries (Norway, Italy, China and USA), which will provide stronger conclusions of causality. This project will contribute to knowledge advancement of the health and social psychology fields by providing an overarching framework to describe public responses toward present and future pandemics. The project output will also have a societal and policy impact by contributing to the management of the crisis both from short- and long-term standpoint. Policymakers can not only derive relevant feedback from predicting public reactions for their application of specific policies, but also anticipate and adjust to the fluctuations in public reactions to real societal changes.",2020,2022,HØGSKULEN PÅ VESTLANDET,484000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Americas | Europe | Western Pacific,,,,Norway,Norway | Italy | China | United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C03621,unknown,COVID-19 Supply Chain Task Force,"The current scramble under COVID-19 for PPE and other critical goods is reminiscent of the Ebola epidemic in 2014. The strain on global supply chains resulting from COVID-19 is not limited to PPE, tests and ventilators. There is a real risk it can spread to other critical goods, including generic medicines. Similarly, the demand for antibiotics may outstrip production as COVID-19 causes serious secondary bacterial infections such as pneumonia. This complex and poorly understood dynamics interconnectedness requires a global system perspective and analysis. Extant literature on medicine and health commodities supply chains has failed to conceptualise and model such supply chains as systems that must adapt from stable situations to crises and back to stability again. There is limited understanding of private-public-partnerships, procurement, contracting, and regulation. To combat the problem of lacking coordination and preparedness, we need to look beyond single countries and single crises to the complex system of global supply chains capable of producing, stockpiling and distributing essential supplies. By establishing and coordinating global preparedness stockpiles of critical goods, framework agreements with suppliers, surge capacities that can be made quickly operational, flexible transport solutions and multiple suppliers of critical goods, we may be able to ensure sufficient slack is built into the system so it can handle stress without breaking down. This project intends to explore these solutions and others to allow governments to prepare and react nimbly. The COVID-19 Supply Chain Task Force constitutes of more than 20 researchers/practitioners from Jimma University Institute of Health, BI Norwegian Business School, St. Pauls Hospital in Ethiopia, and Norwegian Institute of Public Health with strong backgrounds in medicine, health supply chains and analytics and two decades of research in humanitarian logistics, particularly preparedness issues.",2020,2022,STIFTELSEN HANDELSHØYSKOLEN BI,322960,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Africa | Europe,,,,Norway,Norway | Ethiopia,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C03622,unknown,Information Systems for Emergency Diseases Emergency Response to the Covid-19 Pandemic - supporting global and national surveillance,"During epidemics from emerging diseases, WHO guidelines and local circumstances change rapidly. Hence, information systems for operative health workers as well as epidemiological managers should change at the same speed. A consortium for supporting less developed countries with a COVID-19 information system, funded by NORAD, has been set up and is working with 40+ countries. The consortium delivers updated versions every week based on new requirements from the countries and WHO. The research project will generate knowledge on how a consortium can manage such rapid changes to be carried out effectively when there are thousands of end users, travel restrictions, a high performance pressure, and in countries where there is a shortage of skilled health workers, health information systems specialists, unstable electrical power and internet. The research will investigate the system and its development and change process in three countries; Ghana, Palestine and Sri Lanka, representing different cultural regions. The project will have partners in these countries. Also, the global consortium will be studied. The first evaluation will address all direct users with a survey and all members of national and global teams with qualitative interviews. Based on this data and computer logs, an assessment of the system and of the rapid development process will be carried out. Research papers and reports to the consortium and countries including recommendations for changes in the system and in the development process. will be written. This assessment will also be presented to the consortium national teams and selected users after 6 months. A repeated evaluation will take place month 12-18, and a second round of dissemination back to the developers and users will take place. Since no research of such rapid system development cycles has been found in the literature, the conclusions from two evaluations will constitute new knowledge.",2020,2022,UNIVERSITETET I OSLO,550000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Africa | Eastern Mediterranean | Europe | South-East Asia,,,,Norway,Norway | Ghana | Palestine | Sri Lanka,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C03623,unknown,The Smartphone Pandemic: Mobile technologies and data in the COVID-19 response (SMARTPREP),"Will people let public health authorities track their movements through mobile phone data as they seek to establish the effectiveness of Covid-19 countermeasures like physical distancing, school closures and travel restrictions? Until recently, such questions seemed unfathomable outside of authoritarian regimes. However, the COVID-19 pandemic response has seen the rapid introduction of digital innovations like smartphone apps and mobile data in countries' efforts to manage the crisis. New partnerships between governments and tech companies and new legal injunctions passed without public oversight have created a 'data governance crisis of international concern' that seems set to fundamentally alter the way we think about privacy in relation to the public good. The SMARTPREP project provides the first investigation of the political, social and ethical implications of new uses of digital innovations in the COVID-19 response. It will analyse global data governance norms and provide case studies of Norway and Sierra Leone. Norway is currently at the forefront of experimenting with digital innovations as part of its effort to stem its outbreak, while Sierra Leone is drawing on experience of using smartphone tech during the Ebola crisis in 2014-2015 to prepare for a likely outbreak there. The project will explore how political and cultural differences affect public responses to digital innovation in times of crisis, while established relationships between the two countries around health information and development aid will make it possible to study instances of policy and technology transfer. The project will provide policy-relevant knowledge about how digital innovations affect the way societies think of, prepare for, and respond to pandemic risk, and novel insights into how the use of digital innovations to fight the pandemic can challenge core societal values such as democracy, privacy and trust, with potential implications for the effectiveness of countermeasures.",2020,2022,UNIVERSITETET I OSLO,388850,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Africa | Europe,Digital Health | Innovation,,,Norway,Norway | Sierra Leone,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Policy research and interventions",2020 +C03624,unknown,"SARS-CoV-2 infection and COVID-19 in women and their young infants in Kampala, Uganda","Uganda's first confirmed COVID-19 case was recently identified by our collaborating partner in Entebbe. By 29th of March, 33 cases had been confirmed. The high urban population density, extensive and unavoidable social interaction in urban and rural areas, in some areas compounded by challenging hygienic conditions, represent major challenges to the containment of the COVID-19 epidemic in the country. To obtain a population-based description of the evolving COVID-19 epidemic, we will enroll women in labor, and follow them and their young infants for 14 weeks. Concretely, we will describe the evolving epidemic in three neighborhoods in Kampala and identify risk factors for SARS-CoV-2 infection and for COVID-19 as well as its health consequences in our study participants. While the women are likely to mirror the general young adult population with respect to the infection and the disease , the study will also have a particular focus on the large vulnerable group of HIV-positive women and their babies. By including data from a large ongoing randomized controlled trial, an interrupted time-series analysis in both HIV-1 positive mothers and their young infants will describe the impact not only of COVID-19 but also of the recently implemented restrictions on people's movement. We will also examine how these and other measures to contain the epidemic are understood and experienced by women and their families, and explore possible implications for health seeking behaviors. We will also examine the health consequences, beyond that of COVID-19, with the intention of helping to realign the implemented actions to balance their population benefits and risks and suggest strategies to mitigate the latter. The proposed project also encompasses an expansion of a large ongoing randomized controlled trial to examine if BCG vaccination protects HIV-1 exposed young infants not only against Possible Severe Bacterial Infection but also against COVID-19.",2020,2022,UNIVERSITETET I BERGEN,550000,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Africa | Europe,,,,Norway,Norway | Uganda,"Clinical characterisation and management | Infection prevention and control | Vaccines research, development and implementation | Policies for public health, disease control & community resilience | Health Systems Research",Prognostic factors for disease severity | Restriction measures to prevent secondary transmission in communities | Pre-clinical studies | Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2020 +C03625,unknown,"Emotional Contagion (EmotiCon): Predicting and preventing the spread of misinformation, stigma, and anxiety during a pandemic","The EmotiCon project has four interrelated work packages (WPs). WP1 organizes and administrates the grant and disseminates the project's findings. WP2 and WP3 involve the development and execution of social media analysis and an online survey of a representative Norwegian sample, respectively. WP4 will construct a multi-agent artificial intelligence model for analyzing and forecasting the spread of anxiety, stigma and misinformation in social media and offline networks in the wake of COVID-19. That computational model and its simulation experiments will be informed by the data from WP2 and WP3. All WPs will involve the close collaboration between the core research team at NORCE, their international advisory collaborators, and ten municipalities in Norway that have already agreed to participate in a user reference group (these municipalities represent about 30% of the Norwegian population). The Emoticon project will provide new computational tools for assessing and altering the dynamics of emotional and behavioral contagion during public health crises. Our team has already published computational models with the ability to simulate the effect of disease contagion threats on the attitudes and behaviors of human populations. Simulated agents have cognitive architectures and weighted social network ties that affect beliefs and behaviors based on social psychological theories such as 'terror management theory.' They have been empirically validated in relation to real world data. We will adapt these models to simulate the social contagion effects of disease contagion threats under a wide variety of parameters, including those of poorer countries. This will provide stakeholders with an empirically validated 'artificial society' that can serve as a simulation platform within which they can experiment with intervention strategies designed to mitigate the spread of anxiety, stigma, and misinformation during the COVID-19 crisis and future pandemics.",2020,2021,NORCE NORWEGIAN RESEARCH CENTRE AS AVD KRISTIANSAND UNIVERSITETSVEIEN,343310,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Policies for public health, disease control & community resilience",Communication,2020 +C03626,unknown,"Pandemic Rhetoric, Trust and Social Media: Risk Communication Strategies and Public Reactions in a Changing Media Landscape (PAR-TS)","PAR-TS will study 1) the current communication strategies of public health authorities, 2) the role of social media in the crisis; 3) reactions in the public in terms of trust (institutional, social, media), fear and behavioral change, and, finally, 4) potential risk/crisis communication strategies for future pandemic outbreaks. A cross-disciplinary team drawing on political science, media and communication studies, data science, health and civil society studies is put together. The project is based in three academic institutions - Dep. of Media and Communication (IMK), the Institute for Social Research (ISF), and SINTEF - in close collaboration with three key institutions in informing the public - the Norwegian Institute of Public Health (NIPH), the Norwegian Broadcasting Corporation (NRK), and the Association of Norwegian Editors (NR). In addition, two market research companies - Opinion and Kantar - are partners. Focusing on Norway as an empirical case, PAR-TS lays the ground for future comparative studies through the close interaction with a strong network of international scholars participating in an advisory board. PAR-TS pulls together strong methodological expertise that is necessary to address the negotiations of trust between public authorities and citizens. Communication strategies are studied through interviews with communication personnel in the public health institutions and textual analysis of public communication. For the study of interactions in social media, a large scale quantitative and qualitative analysis will be conducted of discussions about corona and the health authorities' handling of the crisis. Finally, population-based representative surveys before, during and after the crisis will enable the study of how citizens receive and act on information, centered on the roles of different types trust. The produced knowledge in PAR-TS will strengthen preparedness and handling of future risks and crisis.`",2020,2022,UNIVERSITETET I OSLO,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Policies for public health, disease control & community resilience",Communication,2020 +C03627,unknown,"Fighting pandemics with enhanced risk communication: Messages, compliance and vulnerability during the COVID-19 outbreak","The PAN-FIGHT project will investigate political and social dimensions of the COVID-19 pandemic, by addressing health risk communication in relation to social and cultural dynamics. We will offer new knowledge on how national and local authorities as well as health institutions can enhance their risk communication to mitigate social vulnerabilities. In so doing, we will contribute to improved preparedness, resilience and societal safety. The COVID-19 pandemic provide an unprecedented opportunity for governments, researchers, health systems and the population at large to assess their resilience and improve preparedness. Future pandemic pathogens can be much more sinister. Of paramount interest in this context is how national and local authorities communicate with their citizens about risks associated with the COVID-19 virus. National and local variations in risk communication appear to have triggered similarly varied reactions in the general public, with subsequent impact on vulnerabilities conditioned by social and cultural differences. Bringing together some of Europe and the United States' most competent researchers on risk communication, societal safety and health emergencies, this project will a) investigate to what extent national variations in authorities' risk communication strategies can be linked to the ways in which members of the public adhere to governmental guidelines, requirements and restrictions; b) identify any correlations between risk communication, adherence, and factors such as social capital, age, gender, socio-economic status and household composition; and c) translate this knowledge into internationally aligned, evidence-based, and culturally sensitive risk communication strategies. The greatest risk to this project is the COVID-19 pandemic itself, with unpredictable health effects on those involved and possible prolonged restrictions on mobility and personal contact. We will counteract the latter with a robust digital infrastructure.",2020,2022,UNIVERSITETET I STAVANGER,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Americas | Europe,,,,Norway,Norway | United States of America,"Policies for public health, disease control & community resilience",Communication,2020 +C03628,unknown,"COVID-19 in Norway: A real-time analytical pipeline for preparedness, planning and response during the COVID-19 pandemic in Norway","The rapidly expanding COVID-19 pandemic poses an imminent threat to the human population and the world economy. There is a need for novel data and high quality analyses of the evolving epidemic in order to guide policies. The overarching purpose of our project is to deliver real-time relevant output to guide policies on the actions to combat the ongoing Covid-19 epidemic in Norway. Our vehicle for these outputs is an advanced mathematical model that incorporates population movements from telephone surveillance as well as a series of epidemiological observations, including data from large cohorts and nation-wide registries. The model can simulate and assess the effects of actions that decrease person-to-person contact in the whole population, as well as in subgroups. Mathematical modelling will make projections of scenarios with different mitigation measures. We will combine dedicated analytical capacities with real time data harvesting, and we will interpret trends, the future course of the pandemic, and explore the possibilities for action to guide decision makers despite remaining uncertainty. We will use repeated data on symptoms from more than 200 000 participants in The Norwegian Influenza Cohort (NorFlu) and the Norwegian Mother, Father and Child Cohort Study (MoBa) with extensive information on previous diseases, exposures and life styles, and whole-genome genotyping. We will examine if underlying genetic predisposition to various diseases influence the susceptibility for COVID-19, or the progression of the disease. Using registry data on the whole Norwegian populations, we will include sociodemographic variables from Statistics Norway and data from health registries that include the newly odes for Covid-19 infection in primary and secondary health care. This will enable us to describe the burden of disease caused by this epidemic and analyse long-term consequences.",2020,2022,FOLKEHELSEINSTITUTTET,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C03629,unknown,COvid19 Network Technology based Responsive Action,"Pandemic responders lack a decision support system (DSS) that realizes the characteristics of the vaccine supply chain problem: (a) the DSS must allow balancing different stakeholder objectives related to effectiveness, efficiency, equity, and sustainability; (b) the DSS should satisfy different objectives throughout a planning horizon; (c) the DSS should account for uncertainties in demand and supply; (d) the DSS must address the critical concerns of different stakeholders; and (e) the DSS should consider the dynamic social and technical components of the situation. The CONTRA project aims to develop a DSS for designing an effective, efficient, fair, and sustainable in-country vaccine supply chain while considering uncertainties along with social and technical components. The DSS will be developed based on mathematical modeling and stochastic optimization (for supply uncertainty) as well as machine learning tools (for demand uncertainty) for designing a robust vaccine supply chain. The main focus of the research is on supporting responders in low-income countries to pandemics, such as COVID-19, and their needs to make informed decisions when designing in-country networks for vaccine supply chains. The project will conduct rapid analyses that will provide actionable advice regarding vaccine distribution and delivery to responders in Norway, including crisis managers, and logisticians responding to the COVID-19 epidemic, in response to the on-going COVID-19 outbreak. To accomplish this, the CONTRA project will use the experience of research on developing decision support systems for vaccine supply chains in low-income countries, although the limitations and generalizability of the approach will be considered. The target group of the project is responders and decision-making stakeholders in low-, middle-, and high-income countries required to make decisions for managing vaccine supply chains in response to epidemics and pandemics, and their information needs.",2020,2021,UNIVERSITETET I AGDER,440440,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2020 +C03630,312716,"Early COVID-19 wave in Norway: Social inequality in morbidity, compliance to non-pharmaceutical interventions and labour marked consequences","Pandemics like COVID-19 are one of the most pressing global threats to human life and economic security. The core idea of CorRisk is that infectious disease pandemics created by influenza or corona-viruses have always been more than just a medical problem and that their epidemiology and impact are profoundly shaped by social and economic structures. While the state of the art mainly studies medical risk factors, this project proposes to study the ""forgotten"" socioeconomic risk factors for unequal morbidity, compliance to the NPIs and labor market consequences. Using survey data and regression models, we ask three essential questions: 1) What is the morbidity risks among the socially and medically at risk vs. the general population? 2) What is the compliance to the NPIs among the socially and medically at risk vs. the general population, and whether and which of the NPIs (personal protection, environmental, social distancing and travel related measures) is associated with reduced morbidity for the risk groups vs. the general population? 3) Which social and employment groups will be in most need for economic austerity packages in mitigating the expected negative labour market outcomes (layoffs, losing jobs and income) of the pandemic and the NPIs? CorRisk undertakes finding socioeconomic inequalities in morbidity, NPI compliance and Labour market outcomes. This is a novel approach emphasizing the need to examine risk as a social and not just a medical phenomena. Our new methodological frame will serve future research on (re)emerging diseses. The CorRisk research group has gathered a strong interdisciplinary and international team of infectious disease and work-life researchers and key national policy-makers in the field of infectious diseases and pandemic preparedness. Findings will be pivotal for real-time current health policies; optimizing the NPIs to prevent severe pandemic outcomes by reducing social inequalities, to save lives and social & economic losses.",2020,2021,OSLOMET - STORBYUNIVERSITETET,249590,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Approaches to public health interventions | Economic impacts,2020 +C03631,312769,Corona-undersøkelsen i Trøndelag: Risk stratification of severe COVID-19 infection in children and adults (CUT COVID-19),"The Covid-19 pandemic is caused by the virus named SARS-CoV2, a corona virus closely related to SARS. The spectrum of disease severity of Covid-19 is wide, ranging from mild symptoms in 80% of the cases, to severe illness with hospitalization in 15% of the cases. The final 5% need intensive care, typically including help to breathe. There is currently no vaccine and no treatment targeting SARS-CoV2. Treatment mainly consist of helping the patient coping with the infection and the immune response. There are important knowledge gaps in our understanding of SARS-CoV2 pathogenesis. The majority of patients that need intensive care are older or have underlying diseases. However, we do not know why some people are at higher risk of Covid-19 infection, serious complications or death. Furthermore, the host and pathogen factors that determines the severity and outcome of the infection are not understood for SARS-CoV2. With this project, we aim to adress these questions. We will establish a database consisting of all hospitalized Covid-19 patients in all ages in Mid-Norway. Furthermore, we will establish a biobank including all these patients. These efforts will make it possible to discover genetic, modifiable, microbiological, clinical and phenotypical factors that can predict disease severity and poor outcome. By including children and adults in the same clinical database and biobank, we will be able to address why children seem to be protected from developing severe disease compared to adults. Many patients will have participated in the population based HUNT and Trøndelagsundersøkelsen (>180 000) from 1984-2019, adding significant value to the proposed study. We expect this research project to result in new knowledge of Covid-19 disease that will aid clinicians in determining risk of disease and poor outcome for individual patients. Furthermore, we expect our results to be relevant in the short term (months) treatment of Covid-19 patients in Norway and globally.",2020,2022,ST. OLAVS HOSPITAL HF,550000,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease susceptibility | Prognostic factors for disease severity",2020 +C03632,unknown,Detection and temporal monitoring of SARS-CoV-2 in Norwegian hospitals and other high transmission risk environments (NorCoV2),"The extremely rapid spread of COVID-19 has resulted in a severe global impact. To stem the tide of the current pandemic, reducing transmission rates within populations and understanding the epidemiological dynamics of COVID-19 is of paramount importance. One way to reduce transmission is to reduce exposure, which requires knowledge about the exposure risk in different environments and scenarios. Further, identifying the sources of observed SARS-CoV-2 strains could identify important transmission routes. The NorCoV2 project will utilize environmental sampling in hospital, subway and airport environments, which are all important with regard to spreading infectious diseases. Air and surface samples will be collected weekly for a period of six months. The presence and abundance of SARS-CoV-2 will be analyzed with Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), and samples where SARS-CoV-2 is detected will be direct RNA long-read sequenced on the Oxford Nanopore Technologies (ONT) MinION platform. The results from NorCoV2 will provide information on exposure risk in important infrastructures, examine the effectiveness of cleaning procedures and infection control measures, provide a high-resolution time series analysis of the current outbreak, and perform critical geographic tracking analyses of environmentally observed SARS-CoV-2 strains. Project members include important stakeholders from the hospital and mass transit sector, and the ENVIRION project, which will perform environmental monitoring of SARS-CoV-2 in sewage. The collaboration with ENVIRION will allow for cross-validation of these two separate monitoring approaches. NorCoV2 will also contribute to a large international SARS-CoV-2 mapping effort coordinated by the MetaSUB Consortium.",2020,2021,FORSVARETS FORSKNINGSINSTITUTT,212850,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2020 +C03633,unknown,"COVID-19 outbreak in Norway - Epidemiology, health care utilization and primary care management (CONOPRI)","Primary care is at the very frontline of the COVID-19 pandemic, and the outbreak already has a huge toll on primary care systems. Consequences of a global outbreak on the Norwegian primary care system have previously been demonstrated for the influenza pandemic. Knowledge about primary care management of COVID-19 outbreak, health care utilization and risk factors for severe outcome, can be used to prepare for future outbreaks and improve the patient management. Primary care needs evidence-based knowledge to meet any epidemic at two levels: 1. The system level, which includes plans to handle an overwhelming number of patients, organization of units to avoid transmission to health care workers and other patients, systems for testing, tracing and isolation, as well as patient pathways through the health care system. 2. The clinical level, which includes knowledge about risk factors for severe illness, and mitigation of modifiable risk factors. The primary study objective is to investigate the effect of organization strategies and handling of risk factors for the outcome of patients in primary care during the COVID-19 outbreak. Secondary objectives are to: 1. Identify patient management strategies in primary care and how this is organized in the municipalities in Norway during COVID-19 outbreak. 2. Identify patient management strategies in European countries during the COVID-19 outbreak. 3. Describe patient contacts to out-of-hours (OOH) services and action taken, and to compare the contacts and action taken between municipalities in Norway during COVID-19 outbreak. 4. Examine how the COVID-19 patient utilize the health care system in Norway and identify different trajectories for COVID-19 patient outcome, compared with other patients. 5. Investigate risk factors for severe outcomes of COVID-19 among primary care patients in Norway. Objective 1 and 2 will be answered by questionnaire data from all OOH services in Norway and OOH services in collaborating European countries. Objective 3 will be answered by use of data from the Watchtower Registry with information from seven representative OOH services in Norway. Objective 4 and 5 will be answered by use of linked data from the Norwegian Registry for Primary Health Care (KPR), the Norwegian Patient Registry (NPR), the Norwegian surveillance system for communicable diseases (MSIS), the Norwegian Prescription",2020,2022,NORCE Samfunn/Helse VESTLAND,550000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Clinical characterisation and management | Health Systems Research,"Prognostic factors for disease severity | Supportive care, processes of care and management | Health service delivery",2020 +C03634,unknown,Perceived Risk and Precautions during a Pandemic Outbreak,"During a pandemic, the behaviour of the general population determines the spread of the contagion, the load on medical services, and the ultimate societal impact of a disease. How individual members of the population understand the risk scenario determines their response to a pandemic, which precautions they take, and the social dynamics they engage in. Social and behavioural science is needed to respond optimally to the COVID-19 pandemic. The current project will measure, track and predict the impact of risk perception and communication on (i) individual decisions and behaviour, (ii) motivation and compliance with public advice, (iii) and social dynamics during a pandemic outbreak. PANDRISK will be among the first projects which transfer knowledge to the specific applied topic of human behaviour during a pandemic outbreak. To achieve this, the project will perform the following work-packages: WP1: Survey of psychological variables related to pandemic's early phases already collected WP2: Four longitudinal surveys following up WP1 WP3: Develop and apply smartphone app for tracking pandemic's relation to mental health, movement and social interaction WP4: Various extensions and generalizations of WP2, among them a US sample (New York) for comparison WP5: Project management and communication with stakeholders The transdisciplinary research team includes expertise in cognitive, biological and social psychology, behavioural aspects of safety, medical psychology with psychophysiological measurements, mental health consequences of long-term trauma, public health policy and communication among the general public. The research team is complemented by Scientific advisory board made up of relevant public, private and civil society service providers.",2020,2022,UNIVERSITETET I BERGEN,502700,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,Digital Health,,,Norway,Norway,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Communication | Policy research and interventions | Indirect health impacts | Social impacts",2020 +C03635,unknown,COVID communication: Fighting a pandemic through translating science,"An infectious disease is a special type of health challenge with its potential for rapid incidence growth. When dealing with such exponential growth regarding potential spread, if an imposed societal measure does not feel drastic, it may already be too late. This has strong implications for public health communication. Bringing about attitude change and acceptance for strict regulations requires explaining health science topics so that also non-experts can quickly understand. How to go about to succeed at this is largely unknown. As media habits have changed, video has become a preferred medium constituting almost 80% of all internet traffic. Yet little is known about how to most effectively use video for relaying complex health messages. The aim of this study is to develop effective, evidence-based video communication for translating complex but important health messages about infectious diseases and pandemics, using COVID-19 as a case to learn and prepare society for handling also future pandemics. Creating effective science communication requires interdisciplinary collaboration, and the project will bring together health professionals and scholars, media creatives, psychologists, statisticians and professional communicators. The study population will include representatives from both the general public and decision makers as part of a holistic approach to how health related risk is understood and communicated on all levels. The general population is a heterogenous group and a one-size-fits-all solution is not to be expected.",2020,2022,UNIVERSITETET I STAVANGER,550000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Policies for public health, disease control & community resilience",Communication,2020 +C03636,unknown,"Cohort study of COVID-19 Nested within an RCT of Patients with Community Acquired Pneumonia: Disease severity, Management, and Outcomes","The COVID 19-CAPNOR study brings together a multidisciplinary research team that seeks to conduct research that will contribute to containing COVID-19, optimizing patient management and preparedness to the curre and analogous outbreaks. The Bergen CAPNOR consortium recently received funding from the Research Council of Norway (NORCAP 288718) and co-funding from the Trond Mohn foundation (RESPNOR 815276) to recruit patients hospitalized for community acquired pneumonia (CAP) at the Emergency Department (ED Haukeland University Hospital (HUS), Bergen, into a randomized controlled trial (RCT) to assess the impact of comprehensive ultra-rapid, molecular diagnostics compared to current standard of care on a broad range of clinical outcomes. CAPNOR, comprising a preparatory pilot study and the RCT (n=1390) has received approval from the Regional Ethics Committee (REK; 31935). A limited pilot study (n=100 CAP patients) was successfully completed in February 2020. COVID-19 cannot be distinguished clinically from other pneumonias. We propose to rapidly leverage our knowledge-and-skill base as well as, the established research infrastructure at the ED, HUS (e.g. trained study staff, standardised eCRFs, optimised sampling, molecular diagnostics, biobanking) to include patients with suspected COVID-19 at the start of the epidemic in Norway. The patient-centred, opportunity driven cohort study will contribute to i) understanding natural history, disease severity and susceptibility; ii) identify groups at high risk of serious infection; iii) optimising sampling strategies and triage processes; iv) optimizing patient management; v) optimising virus detection, elucidating compartments of replication and mapping of antibody responses; vi) supporting capacity building, infection prevention and control measures and best practice to protect health care workers.",2020,2022,UNIVERSITETET I BERGEN,537350,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control","Diagnostics | Pathogen morphology, shedding & natural history | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | IPC in health care settings",2020 +C03637,unknown,COVID-19 infection in healthcare workers and the general population,"The first case of COVID-19 infection was identified in Bergen on 28th February prior to the declaration of a pandemic on 12th March 2020. Rigorous testing of all suspected cases in the community was centralised in Bergen providing a unique opportunity to study the pandemic. Building on our proven experience from the swine influenza pandemic, our interdisciplinary consortium covering the community, hospitals and Universities aims to understand key clinical, epidemiological, and immunological characteristics of COVID-19 infection in the general population, hospitalised patients and frontline healthcare workers (HCW). We commenced our study on 6th March collecting baseline pre-exposure and demographics data and serum samples from 613 HCW. These HCW will be followed up upon suspected or confirmed COVID19 infection. All HCW will be followed up after 2, 6 and 12 months to collect exposure history and serum samples for measurement of specific antibodies. We are the first in Norway to establish serological assays and have confirmed that only infected people have antibodies and no antibodies are found in naive people. In the community, Exposure history and clinical symptoms and blood samples will be collected from all COVIID-19 positive cases and their household/close contacts. We have so far recruited 49 hospitalised patients and will describe the prognostic factors for severe and life-threatening illness and investigate immunological biomarkers for severe disease. We will define levels of population-based immunity to SARS-CoV-2 virus in HCW (exposed and/or infected), community cases and hospitalised patients and evaluate the durability of immunity. Our immunological and epidemiological findings will provide vital information on the ability of the virus to spread in the Norwegian population and in health care services to meaningfully guide future policy decisions at a local, national and international level.",2020,2022,UNIVERSITETET I BERGEN,550000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics | Disease pathogenesis",2020 +C03638,unknown,Technologies for Monitoring COVID- 19 Epidemiological Development,"The overall goal of this initiative is to establish a baseline for new technologies and analytical tools that may support epidemiological observational studies with monitoring capabilities of COVID-19 in a high-risk environment e.g. hospitals to protect healthcare workers from transmission, and to create a safe working environment without contaminated areas, surfaces and objects. The recent findings from Centers for Disease Control and Prevention, UCLA and Princeton University show that the coronavirus can remain active in the air for up to 3 hours, on copper surfaces up to 4 hours, on paper surfaces up to 24 hours and up to two to three days on plastic and stainless steel surfaces. This requires urgent actions to develop technologies and techniques, which can be deployed in healthcare centres to identify potentially infected areas. It is very important to emphasize that this system is not intended for medical diagnosis, as this requires examination of symptoms on a patient and should validated by physical and laboratory tests together with a doctor's assessment. This research project aims to explore the potential and limitations of using a VIS-IR spectroscopic system to measure spectral characteristics in e.g. hospital environments and support epidemiological observations on contamination risk as well as supporting infection prevention and control. The effective application of the proposed methodology may be able to support monitoring infectiousness and support preventing the transmission events. With respect to the eight immediate research actions of WHO in February 2020, this project is focusing on action 4, 5 and 8 to support the epidemiological studies. The consortium consists of technical partners and collaborators (NORCE, NEO, Telops) for hyperspectral imaging, computer vision and machine learning, medical experts (UiB, Haukeland university hospital) for influenza, and viral infections and international labs for clinical analysis.",2020,2021,NORCE Teknologi/Energi AGDER,456500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN) | Trond-Mohn Foundation,Norway | United Kingdom,Europe,Europe,Europe,,,,Norway,Norway,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | IPC in health care settings,2020 +C03777,unknown,Repurposing of Universal and Immunogenic MultiTEP Platform Designed for AD to Develop SARS-CoV-2 Multiepitope Vaccine,"Project SummaryTwo months after the first report of a U.S. death from COVID-19, the death rate is 228 per million people, thetenth highest rate globally. The mortality rate from COVID-19 in those aged 45-54 years is ~5%, and it increasedto 13% in people of 50-60 years old, and sadly 80% of all U.S. coronavirus deaths occurred among people 65years of age and older. To protect people from COVID-19, multiple groups in all over the world have begundeveloping vaccines based on the genetic sequence of SARS-CoV-2. We do not know whether both cellular andhumoral immune responses are necessary for protection against the SARS-CoV-2, but recent data withconvalescent plasma administration into the COVID-19 patients indicate that vaccine inducing neutralizingantibodies could be sufficient for the protection against this infection. More of that, it is possible that a vaccinethat contains currently unknown T cell epitopes of SARS-CoV-2 may induce in immunized subjects a cytokinestorm upon subsequent viral infection that could lead to severe adverse events, culminating in death inparticularly susceptible elderly individuals. To avoid autoreactive T cell activation, using the current AG060965program and other NIA grants, we have developed a universal and extremely immunogenic MultiTEP vaccineplatform for A.D. vaccines targeting pathological Aβ, tau, and α-Syn. Taking advantage of this development wepropose in this Administrative Supplement to create a SARS-CoV-2 vaccine based on proprietary MultiTEPplatform technology. We hypothesize that MultiTEP platform-based vaccine could induce protective neutralizingantibodies in immunocompromised elderly people, including MCI/AD patients. This vaccine may differ from manyothers because it could stimulate adaptive immunity, providing broad coverage of human MHC polymorphismsand activating both naive Th cells and pre-existing memory Th cells generated in response to conventionalvaccines and/or infections with various pathogens during one's lifespan without the activation of harmful virus-specific T cells. Therefore, using our nucleic acid-based vaccine technology we will rapidly generate DNAconstructs by attaching twenty B cell epitope genes from the spike protein to MultiTEP, (ii) select several B cellepitopes that induced virus-neutralizing antibodies in mice, (iii) generate prototype recombinant vaccine, CoV2-2019 targeting simultaneously up to three B cell epitopes associated with production of neutralizing antibodies.This multiepitope CoV2-2019 vaccine will be tested in aged non-human primates (model of age-associatedimmunosenescence) ana transgenic mouse model of A.D./tauopathy (seasonal model of vaccination of elderlypeople and MCI/AD patients previously vaccinated with tau-vaccine, AV-1980).",2020,2022,INSTITUTE FOR MOLECULAR MEDICINE,389064,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2019 +C03778,unknown,Clinical evaluation of SARS-CoV-2 subunit vaccine in a Phase I human clinical study,"AbstractThe novel SARS-CoV-2 is the cause of the coronavirus (CoV) disease (COVID-19) outbreak that currently posea serious pandemic threat to public health. A safe vaccine that rapidly induces long-lasting virus-specific immuneresponses is urgently needed. The CoV spike (S) protein, a characteristic structural component of the viralenvelope, is considered a key target for vaccines against CoV infection, as we and others have previouslydemonstrated for severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS)CoV infections. The safety profile of non-infectious recombinant protein subunit vaccines makes them suitablefor SARS-CoV-2 vaccine candidates for preclinical testing. To develop a SARS-CoV-2 vaccine, we constructedSARS-CoV-2-S1 subunit constructs and established an intracutaneous delivery platform using a novel,dissolving microneedle array (MNA) that enhances the immunogenicity of these subunit vaccines in mice, asdetermined by S1 specific viral titers in serum. Here, we propose to evaluate this PittCoVacc vaccine in a phaseI clinical trial through a single specific aim designed to complete ongoing IND enabling studies, any additionalparallel studies recommended by the FDA, and then to conduct a Phase 1 clinical trial in healthy volunteers.",2020,2020,University of California-Los Angeles,1225641,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +C03779,unknown,A5401 COVID Supplement,ABSTRACTThe AIDS Clinical Trials Group (ACTG) has been selected to lead a Master Adaptive protocol under theAccelerating COVID-19 Therapeutic Interventions and Vaccine (ACTIV) Operation Warp Speed. This trial(ACTG 5401 or ACTIV-2) will evaluate multiple monoclonal antibodies and other small molecules for outpatientCOVID treatment. The Laboratory Center will expand its efforts to include support for COVID-19 clinical trials.,2020,2020,University of California-Los Angeles,3770048,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C03780,unknown,Unraveling the role of the CFTR ion channel in susceptibility to SARS-CoV-2 infection and inflammation,"SummaryThis administrative supplement (under NIH PA-18-591 Administrative Supplements to Existing NIH Grants andCooperative Agreements) seeks funding for research responsive to the SARS-CoV-2/COVID-19 outbreak thatfalls within the scope of the ongoing grant 5R01AI124121-05.The original grant (5R01AI124121-05) is focused on understanding the role of the ion channel Cystic FibrosisTransmembrane conductance Regulator (CFTR) on exacerbated inflammation in the airways. Patients with mutations in this ion channel leading to its malfunction develop Cystic Fibrosis (CF), a disease associated withimpaired bacterial clearance and increased lung inflammation, which ultimately results in lung failure. As an ionchannel, CFTR regulates fluid homeostasis in the lung. In addition, our published studies demonstrated for thefirst time that macrophages lacking functional CFTR had impaired autophagy resulting in excessive inflammatoryprofile. In addition to inflammation, the CFTR ion channel plays also a role in fluid homeostasis in the lung such as edema. Relevant to this Supplement, findings from our group show that mice with reduced CFTR(heterozygous) have increased expression of the severe acute respiratory syndrome coronavirus (SARS-CoV)and SARS-CoV-2 receptor ACE2. The novel emergent pathogen responsible for COVID-19, SARS-CoV-2, is aglobal threat responsible for over 420,000 deaths worldwide as of today and is projected to cause >130,000 deaths in the US alone by the end of June 2020. In Aim 1, we will identify mutations and polymorphisms in theCFTR gene in SARS-CoV-2 positive patients. Aim 2 will determine whether there is a genetic association between CFTR mutations and polymorphisms and severity of respiratory disease. Findings from this study willreveal whether CFTR is a modifier gene to COVID-19. This study will help in the identification of patients prone to respiratory failure or death upon SARS-CoV-2 infection and manage them before they succumb to respiratory failure. Future studies will establish pharmacological compounds that increase CFTR function as newtherapeutics for COVID-19.",2020,2021,OHIO STATE UNIVERSITY,460500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03782,unknown,Real-time syndromic surveillance and modeling to inform decision-making for COVID-19,"Real-time syndromic surveillance and modeling to inform decision-making forCOVID-19 Investigators:Shweta Bansal, Associate Professor, Department of Biology, Georgetown UniversityPej Rohani, Professor, Odum School of Ecology & Dept of Infectious Diseases, University of Georgia Project Summary:The rapid spread of COVID-19 around the United States has created an unprecedentedpublic health emergency. It is now clearly appreciated that smart policy responses to thispandemic require the utilization of reliable, validated transmission models. Models are critical both in terms of forecasting the spatio-temporal spread of the virus, but also inpermitting a rational comparison of alternative non-pharmaceutical intervention strategies.To fill this urgent surveillance gap and inform policy decisions, we propose to model thespatio-temporal dynamics of COVID-19 in the US from novel streams of real-timehealthcare data. Our combination of sophisticated computational and statistical models,together with unique high-resolution data will allow a careful characterization of the burdenof COVID-19 beyond tested cases, discriminate among alternative mitigation policies, and quantify the geographic variation in population immunity as we prepare for the Fall wave.1",2020,2022,GEORGETOWN UNIVERSITY,30885,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2017 +C03783,unknown,Testing the role of NLRP3 and other NLR Family Members in COVID19 pathogenesis,"Abstract:SARS-CoV2 is causing an unprecedented pandemic that is likely to result in millions of deaths, with devastatingeconomic and public health consequences. Approximately 10% of SARS-CoV2 infections result in COVID-19pneumonia that progresses to acute respiratory distress syndrome (ARDS). A growing body of evidencesuggests that the host inflammatory response plays a major role in driving severe disease outcomes. Therefore,it is essential to understand how SARS-CoV2 interacts with the host inflammatory response to drive COVID-19 pathogenesis. Recent studies suggest that bats, which are the natural reservoir of group 2b coronaviruses like SARS-CoV2, have dampened NLRP3 function, which may allow these viruses to infect bats without causing serious disease. This indicates that NLRP3 or other NLR inflammasomes, may play an important role in SARS-CoV2-induced inflammation and thereby drive virus-induced respiratory pathology. Given that these genes andpathways are also polymorphic in humans, this raises the possibility that genetic variation in NLR gene networksmay contribute to variation in SARS-CoV2 susceptibility. Therefore, we propose to take advantage of our research team's unique capabilities in SARS-CoV2 pathogenesis and mouse genetics to directly test whether NLRP3 or other NLR inflammasome pathways contribute to SARS-CoV2-induced disease. We will also test whether genetic variation in these pathways affects disease outcome or virus-induced immunity. This effort willbe further enhanced by a collaboration with Drs. Gary Nolan and Richard Ulevitch (U19AI100627), which will allow us to test whether these genes/pathways are activated during SARS-CoV2 infection in humans. Therefore,the proposed studies, which fall within the scope or the parent grant U19AI100625, achieve three critical research goals by: 1) testing the role of NLRP3 and related pathways in driving SARS-CoV2 disease pathogenesis, 2) testing whether genetic variation in these pathways affects SARS-CoV2-induced inflammatory responses or adaptive immunity, and 3) developing novel mouse models that reproduce key features of COVID-19 disease pathogenesis and inflammation.",2020,2022,University of North Carolina at Chapel Hill,103161,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C03784,unknown,Development and pilot testing of a PrEP communication intervention and integration into existing HIV testing services for female IV drug using clients of a needle exchange,"Project Summary The COVID-19 pandemic mitigation measures are difficult for those with substance use disorder (SUD), whoare more likely to be unstably housed and do not have the economic means to comply. They may also not have access to correct communication messages about their risk. Agencies that provide services to those withSUD, such as syringe exchanges and other harm reduction organizations, have to weigh providing services totheir clients against providing a safe workspace for their employees. These organizations have had to quickly implement response plans in tandem with a fast-moving pandemic, making potential mistakes in bothmessaging to clients and response to COVID-19. This has implications for how best to plan for a futureoutbreak. The primary objective of this study is to understand how best to provide harm reduction services tothose with SUD in an infectious disease outbreak like COVID-19 by understanding how a large syringeexchange plans for and implements a plan and how clients conceptualize an outbreak, prioritize it within thecontext of their other daily risks, and determine what they expect from an agency that provides them harmreduction services. To do this, we will retrospectively investigate how COVID-19 was prioritized by clients of a Philadelphia syringe exchange and how organizational decisions about risk mitigation helped or hurt thatprioritization. Utilizing the RE-AIM Implementation Framework as a guide, we will use a mixed methodsapproach with qualitative in-depth interviews, quantitative mathematically modeled maps from commercialmarketing techniques, and a comprehensive review of planning documents, mitigation policies, and implementation plans. Specific aims are: 1. Assess perceptions of COVID-19 messaging. We will survey clients (n=100) and syringe exchange staff (n=50) and use perceptual mapping and vector modeling analysis to understand how communication of COVID-19 was processed and to inform development of more targeted and effective communication and messaging for future events.; and, 2. Analyze organizational response and COVID-19 plan implementation and develop an action plan. Using the RE-AIM Implementation Framework,we will perform an analysis of framework domains by conducting an implementation assessment. We will use survey data, conduct in-depth interviews with syringe exchange leadership (n=6), staff (n=15) and clients(n=15) and do a comprehensive review of planning documents and implementation of mitigation policies tounderstand how the planning and implementation was carried out. This analysis will then inform strategies forfuture responses through the development of an action plan. These methods aim to elucidate perceptions of COVID-19 messaging and assess decision making around the response from all stakeholders to better understand how to provide targeted communication and evidence-informed responses to potential new waves of this outbreak or similar future outbreaks.",2020,2021,TEMPLE UNIV OF THE COMMONWEALTH,158500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2018 +C03785,unknown,Developing a Multi-epitope Pan-Coronavirus Vaccine,"SUMMARY Humanity is confronting a pandemic caused by the new Corona Virus 2 (SARS-CoV-2) infection. Our long-term goal is to develop a potent prophylactic pan-Coronavirus vaccine to stop/reduce past, current andfuture Coronavirus infections and/or diseases. While SARS-CoV-2-induced antibody and CD4+ and CD8+T cell responses are critical to reducing viral infection in the majority of asymptomatic individuals, anexcessive proinflammatory cytokine storm appears to lead to acute respiratory distress syndrome in manysymptomatic individuals. Major gaps: Identifying the epitope specificities, the phenotype and function of Bcells, CD4+ T cells and CD8+ T cells associated with ""natural protection seen in asymptomatic individuals(those who are infected, but never develop any major symptoms) should guide the development of a futurecoronavirus vaccine. Preliminary Results: We have made significant progress in: (A) Identifying a prioripotential human B-cell, CD4+ and CD8+ T cell target epitopes from the whole SARS-CoV-2 genome; (B)Identifying ""universal"" epitopes conserved and common between: (1) previous SARS and MERScoronavirus outbreaks, (2) current 4388 SARS-CoV-2 strains that now circulate in the United States and184 other countries; and (3) SARS-like coronavirus strains currently found in bats that have the potentialto produce future human outbreaks; (C) Applying our scalable self-assembling protein nanoparticles(SAPNs) antigen delivery platform to produce prototype multi-epitope pan-Coronavirus vaccinecandidates, that incorporate conserved protective epitopes from human and bats Coronaviruses, anddemonstrated their B- and T-cell immunogenicity in HLA transgenic mice; and (D) Generating a novel ""humanized"" susceptible HLA-DR/HLA-A*0201/hACE2 triple transgenic mouse model in which to testthese vaccine candidates. Our hypothesis is that one of our pan-Coronavirus vaccine candidates,containing conserved ""asymptomatic"" SARS-CoV-2 B- and T-cell epitopes that are mainly recognized bythe immune system of ""protected,"" asymptomatic individuals would protect from SARS-CoV-2 infection anddisease, upon intranasal delivery. To test this hypothesis our Specific Aims are: Aim 1: To test in vitro the antigenicity of conserved Coronavirus epitopes, we recently identified from the whole SARS-CoV-2 genome, using blood-derived antibodies, CD4+ T-cells and CD8+ T-cells from SARS-CoV-2-infected symptomatic vs. asymptomatic individuals. The immunodominant conserved ""asymptomatic"" epitopes willbe identified and used in our multi-epitope pan-Coronavirus vaccine candidates. Aim 2: To test in vivo the safety, immunogenicity, and protective efficacy of highly conserved multi-epitope pan-Coronavirus vaccine candidates, delivered mucosally, to our novel ""humanized"" susceptible triple transgenic mouse model. Successful completion of this preclinical vaccine project is expected to identify a broadly protective pan-Coronavirus vaccine candidate that could quickly proceed into an FDA Phase 1 clinical trial.",2020,2025,UNIVERSITY OF CALIFORNIA-IRVINE,745410,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies,2020 +C03786,unknown,Pooled and conventional nucleic acid testing strategies for SARS-CoV-2 to screen direct care research staff and protect HIV patients,"ABSTRACT An outbreak of serious pneumonia caused by a previously unknown viral pathogen, severe acute respiratory syndrome coronavirus (SARS-CoV-2), emerged in Wuhan, China in December 2019. Inadequate access totesting has limited our understanding of the extent of this new epidemic in the U.S. A cost effective accurate andrapid testing strategy is urgent to fill this gap.This administrative supplement to the UCSD Collaborative HIV Clinical Trials Unit (CTU) to screen all patient-facing research staff and a proportion of research participants is directly responsive to PA-18-591 and NOSI AI-20-031 as it may allow safe resumption of key research services at our three U.S. Clinical Research Sites (CRSs)(UCSD Antiviral Research Center [AVRC] CRS, the University of Southern California [USC] CRS and theUniversity of Colorado Hospital [UCH] CRS), serving persons with HIV (PWH) who may be at higher risk forCOVID-19. Continuity of research coordinated with care is critical in progress toward ending the HIV epidemicwithout putting staff and participants at risk for COVID-19 acquisition in the research setting. No other local government or health systems are undertaking this approach. Our goal is to implement and evaluate a cost-effective screening approach to determine the prevalence of SARS-CoV-2 in asymptomatic research staff who are in direct contact with PWH and research participants being seen for study visits, identify new incident infections and potentially prevent asymptomatic carrier transmission ofSARS-CoV-2 to PWH. This proposal is conceptually innovative in that it applies nucleic acid test (NAT) pooling techniques to save testing supplies, personal protective equipment and money to address an immediate need for increased testing. As there are no technical barriers, testing can start immediately.We will screen (1) direct care research personnel 3 days/week at UCSD (n=40) and weekly at USC (n=8) and UCH (n=20) for asymptomatic SARS-CoV-2 and (2) a subset of 10 research participants at each site every testing day. Self-collected nasal swab samples will be tested using a NAT pooling platform (UCSD AVRC CRS)or individual RT-PCR based commercial SARS-CoV-2 testing (USC and UCH CRSs). Our rationale is that by leveraging our CTU expertise in pooled NAT, the infrastructure capacity of the three CRSs and the San Diego Center for AIDS Research (CFAR), we will implement and evaluate a cost-effective screening approach to determine the prevalence of SARS-CoV-2 infection and SARS-CoV-2 immune response (i.e. seroprevalence) among direct care research staff and returning research participants (Aim 1) and todetermine the test characteristics of pooled testing (UCSD AVRC) compared to individual RT-PCR basedcommercial SARS-CoV-2 testing (USC and UCH CRSs, Aim 2). Once validated, this approach can be deployed in other settings to help ensure safe return to work procedures or in high-risk settings such as healthcare workers in cancer or HIV clinics or nursing homes.",2020,2020,UNIVERSITY OF CALIFORNIA-SAN DIEGO,845588,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C03787,unknown,Omics analysis of HIV during synthetic opioid exposure,"Abstract In December 2019, an outbreak of pneumonia of unknown cause occurred in Wuhan, China, and thecausative agent was identified as a novel coronavirus named severe acute respiratory syndrome coronavirus2 (SARS-CoV-2). Additionally, the US is in the midst of a major opioid epidemic largely attributed to synthetic opioids such as fentanyl, and the SARS-CoV-2 pandemic is occurring in parts of the world where recent increases in HIV due to the opioid crisis have been reported. With the SARS-CoV-2 pandemic, there are major concerns about worsening of the opioid crisis. People suffering from addiction are particularly vulnerable to increased infection with SARS-CoV-2 and more advanced disease severity. Many opioids are also associated with immune suppression and enhanced viral pathogenesis. Thus, foundational research on virus-virus and virus-opioid interactions is essential for understanding the impact of SARS-CoV-2 on other co-morbid conditions and for developing robust therapeutic options for limiting viral infection and pathogenesis in high-risk populations.",2020,2021,UNIVERSITY OF CINCINNATI,150215,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2019 +C03788,unknown,High-content optical pooled genome-wide screens of SARS-CoV-2 infection,"PROJECT SUMMARY Identifying gene function and impact on disease biology are overarching aims of life science research in the post-genomic era. Functional genomics also underpins our ability to understand the meaning of genetic variation inhuman populations. However, crucial gaps remain in the functional genomics tool set that will slow our progress in applying genomics to unravel disease biology. Currently, efficiently pooled methods for genome-wide screening require either selection of cells based on growth advantage or physical purification (e.g. by FACS orfor single-cell analysis). Many disease processes are characterized by complex cellular phenotypes including defects in cell or organelle morphology, subcellular localization of molecular components, or cell motility. Other key phenotypes of interest may involve transient states (eg mitosis), cell-cell interactions, or require dynamicassays in live cells (eg, optical recording of electrophysiological activity of cardiac or neural cells). Image-based,high-content screens using overexpression and RNA interference have uncovered novel genes involved incomplex phenotypes, including mitosis, synaptogenesis, and embryogenesis. However, such microplate-based screens of clonal cell populations are not regularly conducted at the genomic scale due to the expense, labor,and automation expertise required. In this program, we developed a new genomic perturbation and screening concept that combines major advantages of pooled perturbation with imaging assays for single-cell arrayedreadout of complex phenotypes. Specifically, we screen pooled genomic perturbations (with CRISPR-Cas9single-guide RNAs) using microscopy to read out phenotypes AND to identify perturbed genes at the single-cell level via in situ sequencing with a sequencing by synthesis approach. This approach is highly scalable because reagent and instrumentation costs are modest (now a few tens of thousands of dollars for a genome-widescreen). Here we request an administrative supplement to apply the technology developed in our existing award to screens for SARS-CoV-2 infection of cell lines with Rob Davey's group at the Boston University NortheastEmerging Infectious Disease Laboratory that is equipped and actively working with high-containment viral pathogens including SARS-CoV-2. This work on antiviral host cell programs is within the scientific scope of the original grant. We will tightly coordinate the rapid execution of optical pooled screens in multiple biological models with Dr. Davey's ongoing conventional CRISPR genomic screening activity. The data-rich genome-wide opticalscreening data will identify new aspects of the SARS-CoV-2-host interface across the viral life cycle and advance our understanding of candidate therapeutics as well as support the generation of new therapeutic hypotheses to address the COVID-19 pandemic.",2020,2021,BROAD INSTITUTE INC,357840,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2017 +C03789,unknown,CVD Risk and Outcome Heterogeneity in Older Adults with Diabetes,"SUMMARY Older people face a higher chance of experiencing serious complications from coronavirus disease 2019 (Covid-19). In particular, older people with diabetes are generally at risk for a number of diabetes-related complications such as heart disease or other comorbidities, which can worsen the chance of getting seriously ill from Covid-19. In a recent study of Covid-19 patients, age, obesity and comorbidities are strongest predictors ofhospitalization, while admission oxygen impairment and markers of inflammation are most strongly associatedwith critical illness (intensive care/mechanical ventilation/hospice/death). This proposal responds to NOT-AG-20-022, ""NIA Administrative Supplements on Coronavirus Disease 2019 (Covid-19)"" through PA-18-591""Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp ClinicalTrial Optional)"" and supplements parent NIA R01 grant (1R01AG054467-01A1) ""CVD Risk and OutcomeHeterogeneity in Older patients with Diabetes"". The goal of the parent grant is to study older patients with diabetes to identify how aging with diabetes affects the risks and development of cardiovascular disease anddisability, so that we can better individualize treatment. We propose a supplementary study, in parallel, to investigate the risk of hospitalization and severe outcomes of Covid-19 in older patients with and without diabetes through analyses of the exceptionally large and racial/ethnically diverse Electronic Health Record (EHR) datasetsin New York City (NYC). Specifically, we will investigate patient characteristics prior to their Covid-19 diagnoses as well as the hospital course of those hospitalized. We will analyze 1) the New York University Langone HealthEHR data (NYULH-EHR); 2) the NYC Health and Hospitals (NYC H+H), a network of 11 NYC public hospitals,long term care centers and clinics; 3) the New York City Clinical Data Research Network (NYC-INSIGHT), anEHR network comprising 20 NYC healthcare institutions, with longitudinally linked data on 12 million patient encounters under a Common Data Model. We will analyze demographics, vital signs, diagnoses, labs,prescriptions, and procedures both pre Covid-19 diagnosis and during hospitalizations. We propose the following3 Specific Aims: Aim 1) Identify risk factors of clinic/ambulatory visit histories and develop individualized risk prediction tools for hospitalization from Covid-19 for older patients; Aim 2) Identify risk factors of clinic/ambulatory visit histories and during hospital stays for severe outcomes from Covid-19 for hospitalized older patients and Aim 3: Cross-hospital assessment and validation of the risk prediction tools in the NYC INSIGHT networks and NYC H+H. The proposal addresses the urgent clinical needs by analyzing the exceptionally large, comprehensive and diverse NYC EHR network in the epicenter of the Covid-19 outbreak in the US. Our extensive experiences with the longitudinal EHR cohort of older patients with diabetes in ambulatory care settings, and our interdisciplinary team of clinicians and biostatisticians well-versed in the state-of-the-art risk-prediction bring ahigh level of scientific rigor to the proposed project.",2020,2021,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,368910,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2017 +C03790,unknown,Kidney Microphysiological Analysis Platforms (MAP) to Explore SARS-CoV-2 Receptors and Inhibitors. A supplement to Parent Grant: Kidney Microphysiological Analysis Platforms (MAP) to Optimize Function,"AbstractCoronavirus disease 2019 (COVID-19) has reached pandemic proportions. Pulmonary andkidney disease are highly prevalent serious consequences of infection with SARS-CoV-2. KidneyInjury Molecule-1 (KIM-1) was identified by Drs Bonventre and Ichimura as the most upregulatedprotein in the injured kidney proximal tubule. KIM-1, also called TIM-1, is a receptor for hepatitisA, Ebola, Dengue and possibly SARS-CoV1 viruses. We hypothesize that KIM-1 is a receptorfor SARS-CoV-2 both in renal tubule epithelial cells and in airway epithelial cells and thatJB1, our newly discovered small molecule inhibitor of KIM-1, and/or nanodisc-incorporated KIM-1 ectodomain can be prophylactic and therapeutic agents for COVID-19.We also hypothesize that we can use the high-affinity binding of KIM-1 and ACE2 to thevirus to create novel diagnostic devices for the virus. In Specific Aim 1 we will characterizethe role of KIM-1 in promoting SARS-CoV-2 entry into kidney and lung epithelia using kidneymicrophysiological analysis platforms (MAPs) on chip and develop an ultrasensitive chip for thehigh-throughput evaluation of potential SARS-CoV-2 binding inhibitors. KIM-1 and ACE2mediated endocytosis of SARS-CoV-2 biomimetic viruses (virosomes) will be compared in kidneyand lung epithelial cells. We will evaluate the effects of KIM-1-mediated spike proteins orbiomimetic virus cellular adhesion and uptake on production of paracrine factors which activateendothelial cells using a kidney-lung MAP. In order to understand binding and/or uptake kineticsof SARS-CoV-2 and characterize potential inhibitors we will develop an ultrasensitivenanoplasmonic triplets-based rapid lateral flow diagnostic chip for a rapid and sensitive inhibitionassay using the kidney-lung MAP. This approach can also be used for point of care diagnostictesting for the virus. In Specific Aim 2 we will evaluate the efficacy of JB1, soluble KIM-1ectodomain and nanodisc-incorporated KIM-1 or ACE2 to inhibit binding and internalization ofSARS-CoV-2 biomimetic viruses by kidney and lung cells using an integrated lung-kidney MAPon chip. Potential inhibitors will be tested to evaluate whether they compete with S-protein and/orbiomimetic virus binding and reduce IL-6 production. Binding affinity and kinetics between KIM-1variants or ACE2 either as free ectodomains or incorporated into nanodiscs and the Spike proteinwill be measured using MicroScale Thermophoresis (MST) and Biolayer Interferometry.",2020,2022,BRIGHAM AND WOMEN'S HOSPITAL,251531,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2017 +C03791,unknown,Influence of NSAIDs and AERD on the expression and function of ACE2 - implications for SARS-CoV2 severity,"PROJECT SUMMARY/ABSTRACT SARS-CoV2 requires angiotensin-converting enzyme 2 (ACE2) to bind to host nasal epithelial cells.However, upon binding of SARS-CoV to ACE2, internalization leads to decreased ACE2 activity. ACE2 cangenerate biologically active peptides (Ang(1-9) and Ang(1-7)) which are protective against severe COVID-19-induced lung injury. Therefore, although ACE2 expression in the nasal epithelium is a required entry point for viralinfection, continued high levels of ACE2 activity may paradoxically provide benefit once the patient is infected. Thehost factors that regulate ACE2 expression and activity are not fully known and are missing pieces required toexpand our understanding of the pathogenesis of this disease. In March 2020 a French health minister suggested that NSAID use might be associated with more severedisease presentation in patients with COVID-19. There is now a desperate attempt to understand whetherNSAID use is simply correlated with, or actually causative of, worsened respiratory outcomes. As fever andmyalgias are associated with COVID-19, and both are often treated presumptively with NSAIDs, it is imperativethat we understand the immunological influence of NSAIDs in this disease. There is also considerable concern regarding the potential for more severe COVID-19-related respiratorydisease in patients with Type 2 inflammation, and the subset of patients with aspirin-exacerbated respiratorydisease (AERD) have severe upper respiratory inflammation in exactly the anatomic areas of the sinuseswhere ACE2 expression has been found to be the highest. It is not yet known how the presence of chronicType 2-driven respiratory inflammation affects ACE2 levels in the respiratory tract or the blood. We have collected nasal epithelial cells (for mRNA assessment of ACE2 expression), and both nasal fluidand serum and plasma (for ELISA measurement of the angiotensin-derived peptides as above) which arebanked and are available for immediate analysis. With these, we aim to shed light on two questions that areplaguing the assessment and treatment of patients with COVID-19: 1) Does use of NSAIDs increase risk of severe complications from COVID-19? 2) Are patients with asthma and Type 2 respiratory inflammation at increased risk of severe complications from COVID-19?Completion of these aims would allow us to make recommendations regarding safety of NSAID use inCOVID-19. Many patients are currently choosing to stop their regularly prescribed aspirin and NSAIDs out offear, which we suspect is unfounded. We will also further understand whether patients with severe Type 2respiratory inflammation have different nasal ACE2 expression and angiotensin peptide levels, compared tohealthy controls, which would suggest a differing risk of severe COVID-19 in those patients.",2020,2021,BRIGHAM AND WOMEN'S HOSPITAL,114202,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C03792,unknown,San Francisco Bay Clinical Trial Unit: Expanding COVID-19 Testing in Heavily Impacted Communities in San Francisco,"Project Summary/AbstractAs of mid-May, 2020, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus thatcauses COVID-19 disease, has been diagnosed in more than 1.3 million persons in the United States andaccounted for more than 80,000 US deaths. Identifying persons infected with SARS-CoV-2 before theypresent to health care can reduce transmission and flatten the epidemic curve. The San Francisco BayArea was particularly hard hit early in the COVID-19 pandemic in the United States, and like many partsof the United States, has substantial racial/ethnic disparities in the distribution of cases of COVID-19 inthe City. The eastern parts of the City have the highest case rates, with most heavily impactedcommunities including the Mission, Bayview and Sunnydale neighborhoods, and the Tenderloin, butrelatively few COVID-19 testing sites exist there. In addition, outbreaks have been occurring incongregate living situations in San Francisco, where testing can be difficult to perform. We plan toincrease SARS-CoV-2 testing through 2 low-barrier testing approaches to identify previouslyundiagnosed persons. First, we will use a mobile testing unit to reach persons in facilities andneighborhoods where COVID-19 rates are high. Second, we will conduct testing through a communitymobilization event in a heavily impacted neighborhood in the southeast San Francisco, testing morethan 3000 persons over a four-day time period. We will integrate HIV testing into SARS-CoV-2 testing, asrates of HIV testing have dramatically declined since the beginning of the COVID-19 pandemic, and thereis substantial overlap in the populations at risk of both types of infection. These activities will have theadditional benefit of increasing capacity at the 2 Clinical Research Sites of the San Francisco Bay ClinicalTrials Unit to conduct COVID-19 research, including trials of vaccines and therapeutic interventions.",2020,2020,PUBLIC HEALTH FOUNDATION ENTERPRISES,600000,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics,2020 +C03793,unknown,Probiotics that moderate pH and antagonize pathogens to promote oral health,"Abstract/SummaryCommensal oral streptococci are the most abundant bacteria in the biofilms that colonize the hard and softtissues of the human oral cavity and many areas of the nasopharynx. These health-associated bacteria employmultiple diverse adhesion strategies and produce a spectrum of compounds and macromolecules that inhibitthe colonization and virulence of pathogens. With support from R01 DE25832, a large collection of commensaloral streptococci has been isolated from healthy subjects, then characterized at the phenotypic and genomiclevels for properties that may promote oral and systemic health. Here, we propose to screen these highlydiverse strains for their ability to bind to and degrade purified SARS-CoV-2 surface proteins and to interferewith CoV-2 Spike protein engagement of the viral receptor, ACE2. Standard methods will then be used toidentify the streptococcal gene products that mediate inhibitory activities. Defined mutants and overexpressingstrains will be utilized to confirm the results. Though not a focus of this Urgent Revision application, it isnoteworthy that, as part of DE25832, we have developed a mouse model in which we can establish variouscommensal streptococci in the oral cavity, then challenge the commensal-colonized mice with a pathogen(s).Such a model could be adapted to in vivo animal challenge studies. Importantly, novel systems for formulationand delivery of one of our commensal strains have already been optimized through an internationalcollaboration, and thus we are well positioned to rapidly translate our in vitro findings to clinical trials of atherapeutic probiotic intervention.",2020,2021,UNIVERSITY OF FLORIDA,215292,Bacteria | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03794,unknown,Endothelial Cell and Cardiomyocyte Dysfunction in Children with Kawasaki disease-like SARS-CoV-2 Induced Immune Activation,"Project SummaryIn the wake of COVID-19 pandemic, fever with severe systemic inflammation and shock, known as PediatricInflammatory Multisystem Syndrome (PIMS), has evolved as a new threat to children. PIMS was originallyreported in Western Europe and the number of cases is rapidly increasing in the U.S. A hallmark of PIMS hasbeen heart failure leading to shock and the absence of significant pulmonary disease. The clinical presentationin these patients shares many features with Kawasaki disease (KD), the most common cause of acquired heartdisease in children, which itself can present with distributive shock requiring inotropic and vasoactive support inthe intensive care unit. Several PIMS patients are either SARS-CoV-2 PCR positive or have developedantibodies against SARS-CoV-2, suggesting that PIMS is an immune-mediated reaction to antecedent exposureto the virus. Curiously, at the same time that patients are being diagnosed with PIMS, the numbers of childrenwith typical KD has increased dramatically in these same regions. The emergence of PIMS is so new and sorapidly evolving that there are literally no publications, treatment guidelines or clinical trials related to theseseriously affected pediatric patients. Through our network of 30 pediatric centers participating in KIDCARE, ourcomparative effectiveness trial for treatment-resistant KD funded by PCORI, we are collecting patient data andclinical samples to support the work proposed here. The goal of this administrative supplement is to analyzedemographic, clinical and laboratory data in conjunction with assays using patient cells and sera, whichwill allow us to study the relationships among SARS-CoV-2 infection, typical KD, and PIMS and to modeldifferent therapeutic strategies against PIMS. Three specific aims are proposed to achieve this goal. SpecificAim 1 will profile and compare clinical features of PIMS and typical KD. Demographic and clinical data and theneutrophil response to intravenous immunoglobulin (IVIG) will be compared between these two illnesses.Cytokine profiles and inflammatory markers in plasma from acute and subacute PIMS and typical KD will alsobe compared. Specific Aim 2 will elucidate molecular features of PIMS and compare with typical KD. We willuse RNA-seq, ELISA, and Western blot analyses to profile changes in levels of molecules related to inflammation(e.g., TIFA, NFkβ, NLRP3-inflammasome, IL-1, IL-6, TNFα) and cardiovascular health (KLF4, miR-483, ACE2)in endothelial cells and cardiomyocytes. Specific Aim 3 will test the efficacy of drug therapy for PIMS bycomparing the in vitro effects of intravenous immunoglobulin, steroids, and anakinra on inflammatory pathwaysand cardiovascular biomarkers in endothelial cells and cardiomyocytes treated with sera from acute PIMSpatients prior to therapy. The synergistic expertise of the investigative teams in this multi-PI supplement providesa unique opportunity to understand the clinical features, molecular basis, and efficacy of drug treatment of PIMSas compared to KD.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN DIEGO,727650,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2018 +C03795,unknown,"Epidemiology, transmission and immunology of COVID-19 in nursing home residents","During late 2019 and the first weeks of 2020 the suspected etiological agent of a large cluster o fpneumonia cases in the Chinese city of Wuhan was identified as a novel coronavirua. SARS-CoV-2 causesCOVID-19, and has erupted as a pandemic in a matter of months. As of 3/30/20 WHO states that there are729,100 confirmed cases globally and 34,689 deaths with the US now having the most cases. Currently novaccines or proven effective therapies exist, leaving transmission control measures to rely on draconianinfection control procedures. Exceptionally high rates of severe infection requiring hospitalization, intensivecare and respiratory support paired with unprecedented restriction of person-to-person contact has resulted inpreviously unseen global consequences on individuals' health, mortality, travel, quality of life and theeconomy. A report of, 72,314 cases in Wuhan resulted in an enormous case-fatality rate of 14.8% in thoseaged ≥80 years, 8.0% age 70-79 years, and 2.3% overall. COVID-19 has spread to 30 nursing homes (NH) in the Seattle area as of March 30th and over 150 NH nationally by March 23rd. The first 120-bed NH in Seattle had 81 COVID+ residents, resulting in 35 deaths atmortality rate of 29%. Importantly, at least 47 staff also developed symptoms or were COVID+. Thesemortality rates highlight the consequence of our current inability to detect infection and monitor transmissionin care facilities with a large number of staff that care for a high-density resident population that is the mostvulnerable to infection. There are over 15,000 NH in the US providing housing to over 1.4 million individuals.These NH residents are typically very elderly, frail, and have multimorbidities. Many millions more within the US share a similar clinical status but live in assisted living or at home where family care for them. The need to understand vulnerability, transmission and develop efficacious therapeutic strategies for COVID-19 in the NH resident is absolutely critical. One of the greatest challenges in an infectious disease outbreak is in determining which patients have mild forms of illness and may be quarantined in place and which patients have or may progress to severeforms of illness and require additional care or hospitalization in another facility. Furthermore, the early identification of those patients that will progress to severe forms of the disease needing further admission tothe ICU is crucial to increase their chances of survival. Here we propose to conduct a surveillance and transmission study through which we will obtain samples that allow us to identify early biomarkers of COVID-19 disease severity or potential for disease severity, that could be used with clinical information to assistclinical decisions in a predictive fashion to stratify patients to the appropriate level of care. Aim 1. Epidemiology: Determine the incidence and prevalence of asymptomatic, presymptomatic, and symptomatic COVID-19 in long-term care residents and the clinical course of their infection longitudinally. Aim 2. Transmission: Assess frequency and dynamics of SARS-CoV-2 transmission after an incident COVID+ resident is identified in the long-term care setting. Aim 3. Immunobiology and Biomarkers: Use systems biology approaches to characterize and follow the virus:host interface and longitudinal host immune responses in COVID+ long-term care residents. Our group has performed multiple NH-based studies in the last 5 years including a series of largecluster randomized studies, each over 800 NH nationally to a multisite vaccine RCT to epidemiologicscreening studies. We are perfectly positioned to obtain the samples and data we propose. In addition,specific to coronavirus we have added Dr. Mark Cameron (Co-PI at CWRU) who has substantial priorexperience with the SARS-CoV outbreak as a lead investigator during that outbreak in 2003 in Toronto.",2020,2021,CASE WESTERN RESERVE UNIVERSITY,1008129,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03796,unknown,ADE-minimized COVID-19 vaccine via epitope focusing and anti-inflammatory innate immunity,"Project Summary Although over 100 COVID-19 vaccines are currently in development worldwide in response to the global publichealth emergency, most or all may suffer from the liability of eliciting anti-viral-spike antibodies (Abs) thatenhance (ADE) either viral infection or COVID-19 disease, upon exposure of vaccinees to circulating SARS-CoV-2 viruses. This phenomenon was observed previously in humans for respiratory syncytial viruses and inpreclinical studies for the closely related SARS and MERS viruses. Notably, none of these viruses currently have a licensed effective and safe vaccine available despite 15 (SARS) to 60 (RSV) years of effort by the scientific community. These facts raise the alarming possibility that all current COVID-19 vaccines that are not rationally designed to avoid ADE may fail, perpetuating the current global health emergency and erodingconfidence in vaccines and in the medical scientific community. Many COVID-19 patients experience near-fatal or fatal immunopathologic ""storms"" in lung, heart and bloodstarting at 7-14 days after onset of symptoms, which is approximately when the antibody response to the virusis rising or peaking. This suggests that immunopathologic ADE of disease enhancement in humans in the current emergency cannot be ignored in vaccine design. A few of the current vaccine candidates take a small step towards avoidance of ADE by restricting vaccine immunogens to the SARS-CoV-2 receptor bindingdomain (RBD), which is theorized to avoid ADE by minimizing immune complex formation without sacrificingvirus neutralization epitopes. Others seek to steer the immune system away from harmful, pro-inflammatoryvaccine responses using viral vectors and adjuvants. We propose to develop a unique vaccine in the pandemic that goes all the way down this road to incorporate only a single, neutralization, B-cell epitope, thereby maximally avoiding both ADE of viral infection and ADE of disease, as well as testing the ALVAC-alum platform we have previously validated for HIV to steer immunity towards a less inflammatory, protective state. Leveraging Rhesus macaques that are already purchased (no cost to this project for purchase), we will produce and test the protection afforded by the single, neutralization, B-cell epitope (Aim 1) as well as theimmune response to the ALVAC-alum platform (Aim 2). The results may set the stage for a rapidly manufactured vaccine to emergently fill the ADE gap in the current COVID-19 vaccine landscape.",2020,2022,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,466125,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C03797,unknown,Genetic screens to find critical host factors for SARS-CoV-2 infection,"PROJECT SUMMARY Emerging and re-emerging viruses cause a constant threat to global health. Discovery and characterization ofcellular signaling pathways that regulate pathogenesis and host defense hold promise for revealing new strategies aimed at enhancing resistance to infection. There are no approved antiviral therapies available forcoronaviruses, including SARS-CoV-2, that cause disease on a large scale, highlighting the need for innovative approaches to develop more broad-spectrum antivirals. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication. Recent breakthroughs in somatic cell genetics have enabled genome-scale genetic knockout screens in human cells to identify cellular factors critical to infection and to dissect innate immune pathways. The pooled genetic knockout approach has several key advantages. First, by using a genome-scale CRISPR library and using pseudotyped virus for entry and a SARS-CoV-2 replicon for RNA replication and transcription, only those genes are selected whose knockout confers a strong resistance to virus infection.Second, because this approach relies on complete knockout of the gene of interest, we select only those genes that affect infection without being required for cellular viability and growth. In this competitive supplement, we propose to use these robust and unbiased knockout screening approaches to identify and thoroughly characterize novel host targets essential for infection by SARS-CoV-2. We expect that these genome-scale screens will elucidate promising cellular targets that could be used to develop host-directed antiviral therapy.",2020,2023,STANFORD UNIVERSITY,121561,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03799,unknown,Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19,"Project Summary In December 2019, a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China, and quickly spreadworldwide, with an increasing number of cases and deaths. In populations naive to this new pathogen, there hasbeen immense inter-individual clinical variability among infected individuals, ranging from asymptomatic infectionto lethal coronavirus infectious disease-19 (COVID-19), which is typically due to pneumonitis and rarely to encephalitis. The infection to severe/life-threatening ratio is estimated to be < 1/1,000 in people <20 years,around 5/1,000 in people 20-50 years, >1/100 over 50 years, and > 1/10 over 80 years. Underlying medical conditions also greatly increase the risk of severe COVID-19. On the other hand, rare cases of apparent resistance to the infection itself have also been identified (viral PCR-negative and seronegative individualsdespite repeated and confirmed exposure). In this context, we hypothesize that monogenic inborn errors of immunity (IEI) may underlie life-threatening COVID-19 infections in previously healthy, young individuals (<50years), whereas monogenic inborn variations of resistance (IVR) may protect other individuals from SARS-CoV-2 infection. Both hypotheses are based on 25 years of studies of a wide range of other viral infections, for which IEI (e.g. influenza virus pneumonitis) and IVR (e.g. resistance to human immunodeficiency virus) have been identified. We will recruit both IEI and IVR cohorts not only in the USA but also, importantly, at the international level; search for candidate disease-causing variants using a cutting-edge strategy developed in our laboratory to analyze whole-exome sequencing (WES) data; and perform in-depth functional studies to characterize the products of candidate genotypes biochemically, and to analyze the corresponding patients' cells immunologically. Our program aims to discover the human genetic and immunological basis of both severe ""idiopathic"" COVID-19 and natural resistance to SARS-CoV-2. Our preliminary results are exciting. In less than 2 months, we and Helen Su (NIAID) have organized the global and growing ""COVID Human Genetic Effort"" (CHGE), with over 400 collaborators and 40 sequencing hubs in 50 countries (www.covidhge.com). In the last month, our own hub sequenced over 100 patients in the IEI cohort and enrolled 2 individuals in the IVR cohort. We have already selected 5 promising candidate genes (IKFZ1, POLR3C,TLR7, IRF7, IL22), which are all involved in anti-viral interferon immunity. Our program focuses on a timely problem (severe COVID in previously healthy young patients and individuals naturally resistant to infection), tests a bold but plausible hypothesis (monogenic basis for both groups of outliers), and uses cutting-edge genetic and mechanistic studies (including the study of leukocyte subsets and induced pluripotent stem cells (iPSC)-derived pulmonary epithelial cells). Our project will permit genetic diagnosis and counseling, while facilitating the development of novel preventive and therapeutic strategies including anti-viral drugs (e.g. aimed at restoring a deficient immunity or blocking viral entry) and vaccines (e.g. aimed at boosting certain immunological pathways) in both genetic and non-genetic cases.",2020,2023,ROCKEFELLER UNIVERSITY,371507,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C03800,unknown,Genetic and Epigenetic Programming of Allergic Airway Inflammation,"ABSTRACT This supplement was written in response to the original NOT-AI-20-031: Notice of Special Interest (NOSI):Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19),and submitted under PA-18-591]. COVID19, caused by the betacoronavirus (CoV) clade SARS-CoV-2, ranges from asymptomatic disease to fatal multi-organ failure. Both innate and T cell-mediated adaptive immunity areimportant for limiting viral replication. Nevertheless, hyperactivation of the immune response in patients withmore severe disease may precipitate a ""cytokine storm"" that results in aggravated morbidity and high mortality.Relevant to the role of immune hyperactivation in COVID disease pathogenesis are our recent studies onasthmatic inflammation showing how allergens and air pollution particulate matter (PM) overcome immunetolerance mechanisms operating in the airway to license tissue inflammation. We identified the JAG1-NOTCH4axis as a key pathogenic mechanism activated by the allergens and PM that acts as a molecular switch to breakdown immune tolerance in the lung and consequently promote inflammation. Along this mechanism we identifiedthat NOTCH4 was selectively induced on lung Treg cells in an allergen and interleukin-6 (IL-6)-dependentmanner, and it directed their subversion into Th2/Th17 effector-like T cells. Importantly, our preliminary results reveal that NOTCH4 expression is upregulated on circulating Treg cells of COVID19 subjects as a function of disease severity, thus implicating this mechanism in disease pathogenesis in COVID19 subjects. Our central hypothesis is that dysregulation of innate and adaptive immunity in COVID19 involves the subversion ofTreg cells in an IL-6 and NOTCH4-dependent manner. Our study team is composed of a multidisciplinarygroup of R01-funded investigators with prior collaborative work, clinical expertise in the care of critically illCOVID19 patients, and research expertise in the role of Treg cells in immunological tolerance. We propose to profile the innate and adaptive immune responses in subjects with mild-moderate and severe COVID19 disease as compared to convalescent and healthy control subjects. We will correlate these changes with NOTCH4expression on circulating Treg cells and the latter's immune regulatory functions. We will also examine the impact of Notch4 expression on transcriptional alterations in Treg and T effector cells in patients with COVID-19. Our studies offer a mechanistic approach to the elucidation of the enigma of immune hyperactivation in COVID19 and the promise to identify targets for precision therapy in this disease.",2020,2021,BOSTON CHILDREN'S HOSPITAL,127625,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C03801,unknown,COVID19 Slide-seq,"Project Summary Cells are the unit building blocks of tissues and organs, thus, to understand how tissues function, it is important to understand where different types of cells reside in health anddisease. In this proposal, we propose to develop a novel spatial genomics platform that willenable multi-modal characterization of tissue structure at the single cell level. This will be revolutionary for the study of tissue organization in development and pathological changes in aging and disease. Our tools will enable us to look at RNA, proteins and regulatory elements in DNA all within the tissue context. We will ensure these novel genomic tools areeasy to use and adopt, which will be especially powerful for pathological settings, where tissue resources are precious, and adoption of tools is limited by ease of use. In addition, we are applying this technology to rapidly develop a deep molecular and spatial understanding of COVID19 infection and its impacts in organs throughout the body. The successful completion of this work will lead to a comprehensive toolset for understanding tissue structure from the perspective of single cell organization.",2020,2023,BROAD INSTITUTE INC,173737,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2019 +C03802,unknown,Development and Deployment of Artificial Intelligence (AI) Driven Methods to Enable Chest X-ray Radiography as an Alternative Diagnostic Method for COVID-19 Pneumonia,"ABSTRACT In this competitive revision, within the same scope of developing and deploying algorithms to make a quantum leap in clinical diagnosis as that in our current U01EB021183, we would like to revise the original aims to add a new Aim to leverage our expertise in the areas of algorithm development and clinical translation to make immediate contributions to combat the COVID-19 pandemic. Specifically, we propose to develop and deploy artificial intelligence (AI) methods to enable chest x-ray radiography (CXR) as an alternative diagnostic tool to diagnose COVID-19 pneumonia, to rapidly triage patients for appropriate treatment, to monitor the treatment response in a contained environment, and to optimize the distribution of the limited medical resources during thecurrent COVID-19 crisis.",2020,2021,UNIVERSITY OF WISCONSIN-MADISON,605070,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03803,unknown,Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection,"ABSTRACT The goals of this proposal are to determine the type I interferon (IFN-I)-mediated antiviral gene program against SARS-CoV-2 infection and to develop novel broad-spectrum antiviral agents (BSAAs) for the treatmentof COVID-19 and other emerging infectious diseases. There are no effective therapeutic agents currentlyavailable in the fight against the global COVID-19 pandemic, in which SARS-CoV-2 has infected millions ofpeople in confirmed cases and caused hundreds of thousands of fatalities. Drugs that target a single virus, like the inhibitors of HIV reverse transcriptase and influenza neuraminidase, require a comprehensive understanding of the lifecycle and disease mechanisms of the virus, which makes development of these drugs necessarily time-consuming. Outbreaks of infection caused by novel emerging highly pathogenic viruses,including avian influenza, SARS, Ebola, Zika virus (ZIKV) and SARS-CoV-2, have become a major concern inthe past two decades. We cannot rely on the traditional virus-specific drugs to treat diseases caused by theseunpredictable emerging viruses. Therefore, it is extremely important to develop BSAAs effective against arange of viruses. My laboratory has been studying anti-viral innate immune responses, particularly the IFN-Isignaling pathway and its downstream gene program, for the last 20 years. While the field has previously focused only on interferon-stimulated genes (ISGs), we have demonstrated that ISGs like cholesterol 25-hydroxylase (CH25H) and IFN-I downregulated genes like fatty acid synthase (FASN) both play important roles in limiting viral infection and replication. We have also identified multiple small molecules for use as BSAAs,including 25-hydroxycholersterol (25HC), the metabolic product of CH25H, and the FASN inhibitor C75. Inaddition, we have extensively studied host innate immune responses to coronaviral infection: we have published multiple papers that explain how the host IFN-I signal transduction pathway is activated in response to infection by coronaviruses like murine hepatitis virus (MHV) and how coronaviruses can suppress their host's innate immune responses through the viral papain-like protease (PLpro). Most importantly, in our preliminary studies we found that 25HC and C75 both have strong inhibitory effects against SARS-CoV-2infection. We hypothesize that the IFN-I-mediated antiviral gene program involves not only upregulation of antiviral ISGs but also downregulation of the host genes required for viral infection and replication. We further hypothesize that by identifying the IFN-I-mediated antiviral gene program against SARS-CoV-2, we will be ableto develop novel antiviral agents to combat COVID-19 and other emerging threats. In this proposal, we will first determine the IFN-I gene program in innate immune response to SARS-CoV-2. We will also develop 25HC,25HC analogs and FASN inhibitors as novel antiviral agents against SARS-CoV-2. We believe our studies will not only determine the IFN-I-mediated antiviral gene program in host innate immune response to SARS-CoV-2infection but also develop BSAAs to treat COVID-19 and other emerging infectious diseases.",2020,2025,University of California-Los Angeles,380328,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C03804,unknown,"Circulating Red Blood Cell Based Nanosensors for Continuous, Real-Time Drug Monitoring","ABSTRACTNanosensor technology for continuous monitoring of proteins in vivo would enable researchers to track thedynamics of biomolecule expression as it pertains to disease pathogenesis or predicting therapeutic efficacy,with results available in real-time. An example where this diagnostic ability would be groundbreaking is in thecontext of understanding cytokine release syndrome (CRS). CRS is a systemic inflammatory response thatarises when the immune system is overstimulated, leading to extreme toxic events such as multiple organdysfunction1. There is now increasing evidence to suggest that the development of severe cases of COVID-19can be attributed to onset of CRS. It has been revealed that serum levels of cytokines like IFNγ, IL-6, sIL-2Rα,and IL-10 can be significantly elevated in patients with severe CRS, before the apparent onset of severesymptoms. However, the use of cytokines as biomarkers of CRS would require a rapid, minimally invasivediagnostic assay, which is currently unavailable, slowing animal studies of COVID-19/CRS. Recently publishedresearch from the Clark laboratory has demonstrated a proof-of-concept DNA-based sensor for minimallyinvasive detection of IFNγ, one of the cytokines that has been proposed as a biomarker for predicting thepotential for onset of severe CRS. This design was inspired by advances in DNA nanotechnology, which enableresearchers to create functional nanostructures with site-specific modifications based on the complementarybase-pairing rules of DNA. The open or closed state of the sensor could be determined through differentialsignals as detected with optical imaging. Drawing from recent advances in DNA origami design and stabilizationtechnology, we hypothesize that we can improve on this work and produce a robust platform for opticalmonitoring of IFNγ in real-time by (1) enhancing the rigidity of our DNA platform and (2) deploying protectionstrategies to ionically stabilize the construct in biological solutions. This project aims to advance current analyticalstrategies for immunological diagnostics by providing researchers with a powerful tool to probe biomoleculedynamics toward in vivo use with existing optical imaging platforms. The one-year project will result in a robusttool developed for animal research. The goal will be to commercialize and distribute the sensor for COVID-19studies, as well as other immune system research.",2020,2021,NORTHEASTERN UNIVERSITY,211086,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Immunity | Disease pathogenesis,2018 +C03805,unknown,Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax,"Project Summary The continuing prevalence of SARS-CoV-2 coronavirus cases has led to an urgent need to developstrategies for identifying patients who are likely to have mild vs. severe disease to optimally allocate healthcare resources. It is also critical that we understand why certain patients develop severe disease. One possiblemechanism is through antibody-dependent enhancement (ADE) a phenomenon well documented for otherviruses including SARS. In order to develop safe and effective vaccines, it is essential that we determinewhether the humoral immune response to Covid-19 induces antibodies that can mediate ADE and tounderstand which aspects of the immune response to the virus correlate with good clinical outcomes.Addressing this knowledge gap quickly is necessary to inform vaccine trials, which are already underway orare about to start. Our multidisciplinary team has the expertise to address the issues described above. As an independentnon-profit research institution, we are nimble and responsive to evolving health needs. Besides studying aspectrum of patients from across Oklahoma, we are uniquely positioned to look at the consequences of SARS-CoV-2 infection for Native Americans. Native Americans have the shortest life expectancy of any ethnic groupin the US with higher rates of nearly every co-morbidity associated with higher mortality with SARS-CoV-2infection (obesity, diabetes, heart disease, and hypertension). Oklahoma is home to 39 federally recognizedtribes and has the 2nd highest number of American Indians (482,760 according to the 2010 census, and highestpercentage, >10%) in the US. Through our Oklahoma Shared Clinical and Translational Resources (OSCTR),we have partnerships with 5 major tribes, urban Indian clinics and the Southern Plains Tribal Health Boardrepresenting all tribes in Oklahoma, Texas and Kansas. Through these and other interactions, we have strongties to obtain samples from Native Americans with SARS-CoV-2 infection and exposure.Specific Aims1. Identify biomarkers and mechanisms of severe Covid-19 disease pathogenesis2. Characterize the humoral immune response to SARS-CoV-2 infection3. Characterize the T cell immune response to SARS-CoV-2 infectionWhenever feasible, we will compare the responses of Native Americans to those of European Americans todetermine whether Native Americans experience worse outcomes to SARS-CoV-2 infection and if so, whichparts of the immune response is/are suboptimal. We will also compare the responses of individuals with mildvs. severe disease. The knowledge gained should lead to better care for individuals with Covid-19 disease.",2020,2021,OKLAHOMA MEDICAL RESEARCH FOUNDATION,832784,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C03806,unknown,CoVPN Vaccine Site Preparation,"Project Summary/AbstractGiven the rapid spread of SARS-CoV-2 infection, the on-going global pandemic, and the risk for seasonalrecurrence there is a critical need to test emerging vaccine candidates in phase 3 efficacy trials. Due toits experience in implementation of global HIVAIDS prevention efficacy trials and its operational capacityto respond to a new global pandemic, the HPTN, in collaboration with the HVTN, is providing operationalsupport for the newly constituted COVID-19 Prevention Network (CoVPN). Preparing for a series oflarge scale efficacy trials, this application outlines aims required to build the infrastructure capacity torapidly implement them over the coming month. The requested funds are to prepare clinical trial sitesfor implementation of these trials. The HPTN will support 30 clinical trials sites in the United States,South America, and Sub-Saharan Africa so they can begin enrollment in NIH supported COVID-19 vaccineand monoclonal trials planned for implementation over the next 6 months.",2020,2020,FAMILY HEALTH INTERNATIONAL,101206482,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C03807,unknown,Ubiquitin Regulation of K Channels in Health and Disease,"SummaryThis proposal is for a COVID-19-related Administrative Supplement for RO1HL142111, ""Ubiquitin regulation ofK Channels in Health and Disease"". We propose to adapt/apply tools and approaches including, nanobodydevelopment and optical assays of membrane proteins, that we have developed for studies in the parent proposalto develop novel solutions for COVID-19. There is an ongoing global pandemic in which a novel Coronavirus,SARS-CoV-2, causes Coronavirus Disease-2019 (COVID-19) that is lethal to a subset of the infected population.To date, there are >1.5 million confirmed COVID-19 cases worldwide with >70,000 fatalities. In the United States,best case scenario projections indicate 100,000 - 240,000 lives will be lost to COVID-19, with a worst casescenario of >2 million deaths. The current pandemic follows two other regional outbreaks of coronavirusesresponsible for severe acute respiratory syndrome (SARS-CoV) in 2002, and Middle Eastern respiratorysyndrome (MERS-CoV) in 2012, that caused epidemics with fatality rates of 10% and 36%, respectively. All threecoronaviruses represent examples of animal to human transmission of infection. Given a high zoonotic reservoirof novel coronaviruses and persistence of close animal/human contact in various parts of the world, the chancesof future viral epidemics/pandemics beyond the current crisis is high. Hence, fatal diseases caused by viralinfections represent current and future widespread public health challenges, highlighting an urgent need forgeneral strategies that can combat not only COVID-19 but also other future viral outbreaks. SARS-CoV-2 is anenveloped virus that gains access to host cells by using a receptor binding domain (RBD) on a viral surface spikeprotein (S) to bind to membrane-bound angiotensin-converting enzyme 2 (ACE2) receptors on target cells.Preventing the SARS-CoV-2 S protein/ACE2 receptor interaction is the main principle behind the beneficialeffects of neutralizing antibodies in recovered patients, and the scientific premise for an ongoing clinical trial foradministration of soluble ACE2 ectodomain. There are ongoing efforts to develop neutralizing monoclonalantibodies (mAb) against SARS-CoV-2 S protein that disrupt interaction with ACE2. While potentially effective,limitations of this approach include high cost, time-consuming, incompatibility with inhalation formulations, andpotential for viral mutations that result in escape from mAb-mediated neutralization. This proposal is based onthe hypothesis that engineered single-domain antibodies (nanobodies) with high avidity for SARS-CoV-2 Sprotein can be generated to overcome some of the limitations of neutralizing mAbs and provide potentialtherapeutic leads for COVID-19. We propose three aims: 1) Isolate and characterize neutralizing and non-neutralizing nanobodies against SARS-CoV-2 S protein; 2) Develop cell-based high throughput fluorescenceassay to probe SARS-CoV-2 S protein/ACE2 interaction and internalization; 3) Comparatively evaluate thecapacity of engineered nanobodies to disrupt SARS-CoV-2 S protein/ACE2 interaction and internalization",2020,2021,COLUMBIA UNIVERSITY HEALTH SCIENCES,337499,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2018 +C03808,unknown,HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals,"This proposal outlines the scientific agenda for the Leadership and Operations Center of the HIV VaccineTrials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4continents dedicated to developing globally effective vaccines for HIV, tuberculosis and now SARS-CoV-2.The HVTN has led HIV prevention science for over 20 years through robust phase 1 and 2 clinicaldevelopment trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizingmonoclonal antibody (mAb) VRC01 undergoing testing in 5 randomized controlled efficacy trials.With the rapid onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in thefield on the contribution of immune functions involved in preventing infection, in modifying COVID-19 disease,and in clearing viral infection. We believe the HVTN is well placed to study these gaps and rapidly deploy thisinformation in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study wepropose initiating an observational cohort study of approximately 400 persons in the United States (22 trialssites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a varietyof risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adultsbetween 18 and 55 years of age and those older than 55 years, and persons with high interest clinical orvirologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolongedviral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims ofthis study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, todevelop and qualify a suite of immunologic assays and reference reagents that will permit detailedinterrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in keypopulations and risk groups, and to characterize presentations of the infection among convalescent individuals.This initial study will tell us much about the adaptive immune responses in persons who have been infectedand recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfullyclearance of infection. It will improve our understanding of the dynamics and duration of responses, as well asthe epitope specificity and other defining signatures, and will inform rational design and testing of preventiveand therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork forprospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study willprepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.Laboratory, statistical and operational experience in this first trial will be invaluable preparation and priming ofnetwork machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVIDPrevention Network in coming months.",2020,2020,FRED HUTCHINSON CANCER RESEARCH CENTER,138462987,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Protocol,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America | Peru,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Immunity | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03809,unknown,Exosome-display as a strategy to enhance the immunogenicity of SARS-CoV-2 vaccines based on adenoviral vectors,"SUMMARY: The emergence of the SARS-CoV-2 coronavirus (CoV) highlighted our lack of preparedness, andhas emphasized the importance of rapidly building capacity in the development of reagents, tools, diagnosticsand therapeutics for SARS-CoV-2 and related CoVs with pandemic potential. An immediate goal is to producea vaccine which can elicit rapid, high-level protective immunity against SARS-CoV-2, ideally following a single-shot. Several candidate vaccines have now advanced into clinical trials. However, a longer term goal is toinvestigate the possibility for a ""universal"" CoV vaccine, a vaccine or prime:boost vaccination regimen whichprovides durable and broadly cross-reactive immunity against CoVs with high potential for spillover from bats.The CoV surface spike (S) glycoprotein is a major target for neutralizing antibodies (NAbs) and T cells, and isan attractive target for vaccine design. NAbs which target the receptor binding domain (RBD) confer protection,but are usually strain-specific and lack breadth. The existence of broadly reactive, protective epitopes outsideof the RBD are not well-characterized. Therefore, vaccines which compare full length or truncated, stabilizedvariants of the S immunogen, could shed some light into potential correlates of protection. Another importantconcern is disease enhancement, which has been observed for related CoV vaccines using selected vaccinedelivery platforms such as the whole-inactivated virus (WIV) vaccine. This has been associated with a Th2-biased immune response and to overcome this issue, CoV vaccines should elicit a largely Th1 biasedresponse. Therefore, studies which aim to compare the phenotype of immunity elicited by different vaccineplatforms, and to different variants of the S immunogen, could help to better understand which components ofthe immune response are optimal in mediating protection, without the risk of immunopathology upon infection.We will develop a potently immunogenic, optimized vaccine platform for SARS-CoV-2 using threeapproaches. (1) Firstly, we will engineer SARS-CoV-2 S in several different forms, a full-length immunogen, asecreted stabilized pre-fusion form or the RBD domain alone. (2) Secondly, we will augment or broadenimmune recognition of pre-fusion S by targeting it to host-derived extracellular vesicles (EVs) includingexosomes in vivo, by generating fusion-Ag constructs which tether Ag to a protein domain highly enriched inexosomes. Exosomes are nano-sized EVs shown to play important roles in cell:cell communication and in theregulation of immune responses, due to their ability to present Ag to T- and B-cells. (3) Finally, we will developnon-replicating, rare species adenoviral (Ad) vectored vaccines which have established protocols for rapidclinical manufacturing and regulatory approval, can be thermostabilized with minimal losses to immunogenicityand have demonstrated safety in human clinical trials. This study will comprehensively evaluate and phenotypethe magnitude and profile of SARS-CoV-2 vaccines in single-shot regimens. These data will provide valuableinformation for the design of subsequent prime:boost regimens and for challenge experiments in the future.",2020,2022,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,466125,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies | Vaccine design and administration",2020 +C03810,unknown,Targeting the Ghrelin System for Novel Opioid Use Disorder Therapeutics,"PROJECT SUMMARYThe coronavirus disease 2019 (Covid-19) pandemic erupted into the midst of the drug overdose crisis in the US.Over 60% of drug overdoses are linked to opioid analgesics, with repeated overdoses indicative of thedevelopment of opioid use disorder (OUD), a growing and life-threatening medical condition. Given that we areunable to decouple opioid-induced pain relief from opioid abuse and OUD at present, opioid analgesics willremain essential in medicine and their use is likely to co-occur with Covid-19 illness. Opioid medications generallyenhance viral replication, pathogenesis, and infectious disease progression, in part via weakening the immunesystem. The SARS-CoV-1 virus is neuroinvasive and neurovirulent and is linked to progressive central nervoussystem (CNS) symptoms (e.g., confusion, delirium, dysphoria), aligning with symptomatology seen in someCovid-19 patients. As for other viruses, SARS-CoV-2 immunopathology and disease progression will prove tobe a function of virus pathogenesis and host vulnerability, one of which may be chronic opioid use in painmanagement and/or OUD. These findings inspire the urgent need to understand how opioids impact specifichost vulnerability factors and cofactors, and how medications proposed to treat Covid-19 affect opioid signaling,particularly within single cells that control CNS actions of opioids. Initial observations suggest that host factorsinvolved in SARS-CoV-2 cellular entry are altered in the brains of heroin users. We recently reported that brain-region specific expression of immune cytokines and chemokines tracks with lifetime fentanyl intake in rats,suggesting that opioid exposure regulates host viral entry and immune function relevant to Covid-19 infection.Given the concurrent Covid-19 and overdose crises, the chronic use of opioids in pain management, the growingproblem of OUD as well as illegal abuse of opioid drugs, we propose two specific aims of immediate relevanceto predicting Covid-19 disease severity and appropriate therapeutics in opioid-exposed OUD patients. Basedupon this premise, we will test the hypothesis that withdrawal from chronic fentanyl self-administration in maleand female rats will impact key targets that mediate SARS-CoV-2 infection in identified single cells in CNS viasingle-nuclei RNAseq transcriptomics (Aim 1) and that acute or chronic Covid-19 medication candidates willalter signaling profiles of opioids (e.g., fentanyl, buprenorphine) in a cellular system (Aim 2). We expect todiscover altered markers of host viral entry and immunological status in identified single CNS cells followingchronic fentanyl self-administration, establishing the potential for enhanced neurological damage in Covid-19patients. We also expect to demonstrate interactions between Covid-19 medications and opioid signaling whichpredict potential interactions in vivo. These innovative aims are consistent with the goals of NOT-DA-20-047 todetermine if opioid exposure is a risk factor for the onset and progression of Covid-19.",2020,2021,The University of Texas Medical Branch at Galveston,237381,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Disease models | Prognostic factors for disease severity | Supportive care, processes of care and management",2019 +C03811,unknown,Characterizing the Functional Architecture of the Necklace Olfactory System,"AbstractSARS-CoV-2 (CoV-2) is a pandemic coronavirus that causes the COVID-19 syndrome, whichcan include upper respiratory infection (URI) symptoms, severe respiratory distress, acutecardiac injury and death. Clinical reports suggest that infection with CoV-2 is associated withhigh rates of disturbances in smell and taste perception, including anosmia. While many virusesinduce transient changes in odor perception due to inflammatory responses, in at least somecases COVID-related anosmia has been reported to occur in the absence of significant nasalinflammation or coryzal symptoms. This observation suggests that CoV-2 might directly targetodor processing mechanisms, although the specific means through which CoV-2 alters odorperception remains unknown. As part of a paper we recently posted to bioRxiv, we queried bothnew and previously published bulk RNA-Seq and scSeq datasets from the olfactory system forexpression of Ace2, Tmprss2 and other genes implicated in coronavirus entry. This analysisrevealed that in mouse and human olfactory epithelium ACE2 transcripts are absent fromolfactory sensory neurons but present in both sustentacular cells and horizonal basal cells. Weperformed a similar analysis in mouse olfactory bulb, which revealed that neurons fail to expressAce2 (either in the olfactory bulb or in the rest of the brain), but that high levels of Ace2expression are observed in vascular pericytes. These preliminary data suggest that non-neuronal cell types are the primary target of SARS-CoV2, and represent the likely mechanismthrough which the virus causes anosmia. However, these preliminary data are based uponsingle cell sequencing, which is biased in terms of the cell types captured, under-representsgene expression, and fails to identify the distribution of Ace2 protein (which is the relevantmolecule for SARS-CoV-2 entry). Here we request supplementary funding to perform in situ,immunohistochemistry and single cell sequencing experiments to comprehensively characterizethe expression of Ace2 and other SARS-CoV-2 entry genes in all cell types in the olfactorysystem. The results of these experiments will have significant implications for our understandingof disease mechanisms, and represents a key first step towards developing strategies foraddressing any long-term olfactory-related sequelae of SARS-CoV-2.",2020,2022,Harvard University,168481,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis",2017 +C03812,unknown,Determinants of Coronavirus Fidelity in Replication and Pathogenesis,"Summary: The SARS-CoV-2 pandemic (COVID-19) threatens the entire world's health, economy and socialstability and is likely to continue for the foreseeable future. The capacity of this virus to cause proteanmanifestations and resist public health control demonstrates its profound evolutionary and adaptive capacity.We have studied the experimental evolution and determinants of fidelity and adaptation of CoVs for more than20 years. The parent grant (R01 AI108197) for this proposed supplement defines the determinants of CoVreplicase proteins in virus fidelity and pathogenesis, and is specifically directed toward understanding the role ofthe unique CoV exoribonuclease encoded in nonstructural protein 14 (nsp14-ExoN). Using SARS-CoV, MERS-CoV and MHV, we have shown that nsp14-ExoN mediates RNA proofreading and is responsible for: i) CoV highfidelity replication; ii) resistance to nucleoside analog inhibitors; iii) virus fitness; iv) evasion of host immunity;and v) virulence in vivo. Engineered mutants of MHV and SARS-CoV lacking ExoN (ExoN(-)) are impaired in allof the above functions and thus define ExoN as an exceptionally conserved and vulnerable virus encoded targetfor inhibition and attenuation. In this administrative supplement, we propose in vitro and in vivo studies of SARS-CoV-2 nsp14-ExoN, with the long-term goal define its role in virus replication and as a target for inhibitors andattenuation. We will rescue SARS-CoV-2 mutants of nsp14-ExoN and define their impact on replication anddisease. In Aim 1, we will introduce mutations into SARS-CoV-2CoV-2 nsp14-ExoN that are known in SARS-CoV, MERS-CoV, and/or MHV to abolish proofreading, alter nucleoside analog sensitivity, impact virusreplication and fitness, or decrease virulence. Recovered viruses will be tested for these phenotypes. In Aim 2,we will select replication-competent ExoN mutants with defined phenotypes for testing in highly relevant humanairway epithelial (HAE) cultures and in a mouse model for SARS-CoV-2 replication and disease. The long-standing and highly productive collaboration between the Denison and Baric labs has already resulted indevelopment of SARS-CoV-2 reverse genetics, initial analysis SARS-CoV-2 recombination, and potential animalmodels, all of which, in combination with our established bioinformatics pipelines, will allow rapid progress onthe proposed supplement aims and will provide data for longer-term detailed studies of the role of ExoN and theviral polymerase. The significance and urgency of these studies is high, as they will rapidly result in identificationof nsp14-ExoN targets for small molecule inhibitors and multiple pathways to stable and universal attenuation ofSARS-CoV-2 and future zoonotic CoVs.",2020,2023,Vanderbilt University Medical Center,318794,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas | Europe,,,,United States of America,United States of America | France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +C03813,unknown,1/5 The Cumulative Risk of Substance Exposure and Early Life Adversity on Child Health Development and Outcomes,"PROJECT SUMMARY / DESCRIPTIONDoes maternal infection by the SARS-CoV-2 virus during pregnancy harm the developing fetal brain or increasethe sensitivity to later developmental and environmental insults? he novel coronavirus (Covid-19) outbreak hasfundamentally altered the child health landscape, ushering in sweeping changes in the social and economicfabric within which children grow. The rapidity of these environment changes, coupled with the relatively noveltyof the SARS-CoV-2 virus and the widespread nature of infections, have presented multiple pressing questions.Among the unknowns that directly affect newborn and child health are: 1. How does Covid-19 infection duringpregnancy effect the developing fetus or subsequent infant neurodevelopment? And 2. How will theunprecedented scale and scope of concurrent environmental changes impact child health andneurodevelopment? Unfortunately, over the course of the outbreak, the impact on children has been slow to berecognized with studies of Covid-19 infection or effects in infants and young children sparse to nonexistent.Moreover, while the health and economic impacts of the Covid-19 outbreak have been felt by everyone, themost severe effects have be felt by racial and ethnic minorities and lower income families. Thus, the mostsensitive families and children already at risk for worsened neurodevelopmental outcomes aredisproportionately and more intensely affected. Studies of newborns and infants are, therefore, critical todesigning effective guidelines of care for expectant mothers, optimizing early care and support for mothers andtheir newborns, and prioritizing pre- and postnatal interventions. This supplement proposal aims to contributeimportant and timely evidence for these outcomes by characterizing neurodevelopmental profiles in infants bornto mothers with and without antenatal Covid-19 infection, and examining the concurrent impact of social,economic, and substance use factors. Building on two existing and on-going studies of infant neurodevelopment(R34DA050284 and UH3OD023313), with deeply characterised longitudinal neuroimaging, neurocognitive,socioeconomic, demographic, psychosocial and biospecimen data, we will first investigate differences in brainstructure, function, and connectivity development from birth to 1yr of age in infants born to mothers who wereinfected by the SARS-CoV-2 virus during pregnancy and born between May 1, and Sept. 1, 2020, compared toinfants recruited at the same time but to non-infected mothers. We will also examine the impact of infectiontiming during pregnancy and symptom severity on brain measures. Next, we will compare these braindevelopment trends to data from children who turned 1year old prior to Jan. 1, 2020, allowing us to examine theimpact of specific environmental factors, including maternal and infant stress, nutrition, sleep health, and parent-child interaction that have changed due to outbreak-related lock-down and social distancing polices. We willfurther look at these environmental factors through a racial and socioeconomic lens, examining differencesacross race and income dimensions.",2020,2021,RHODE ISLAND HOSPITAL,126761,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management | Research to inform ethical issues,"Disease susceptibility | Disease pathogenesis | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2019 +C03814,unknown,CRISPR screens for SARS-CoV-2 Host Factors,"PROJECT SUMMARYIn collaboration with Dr. Wilen (Yale University) and Dr. Goujon (CNRS, France), we will establish cell linemodels and conduct genome-wide CRISPR screens to identify host genes that are necessary for SARS-CoV-2infection. We will first use Vero cells from the African Green Monkey, as they are a well-established model formany pathogens, and we had previously generated a genome-wide library for this species. Preliminary datasuggest that we have also generated human cell lines that can serve as effective model systems, and thesescreens will be conducted as soon as the models are sufficiently validated. Across these screens, we expect tofind host factors that are necessary for infection, such as the surface binding target for the virus, ACE2, andanticipate that the screens will identify additional genes that, when knocked out, prevent viral cytopathiceffects. Additionally, we can modulate the selective pressure to identify factors that, when lost, sensitize thecells to SARS-CoV-2, which will provide a complementary view into host cell biology. Likewise, we will alsoconduct CRISPR activation screens to identify host genes that, when overexpressed, provide protectionagainst infection, which may identify restriction factors that the virus must overcome. Primary screens will bevalidated with secondary pools, which will also allow for testing of genes across more conditions and cell types,establishing the generalizability of the results. Finally, combinatorial screens will be conducted to generateunbiased genetic interaction maps of hit genes, which can identify redundancies that are partially masked in aprimary screen, as well as unexpected synergies across pathways. Focused, mechanistic follow-up of genesidentified by these screens is outside the scope of this proposal, but is of immediate interest to the Wilen andGoujon groups.",2020,2022,BROAD INSTITUTE INC,440000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas | Europe,,,,United States of America,United States of America | France,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03815,unknown,Harvard/Boston/Providence Clinical Trials Unit (Harvard/B/P CTU),"The Harvard/Boston/Providence Clinical Trials Unit (CTU) conducts clinical trials to address research areas ofthree NIAID HIV Clinical Research Networks: vaccines against HIV infection (HVTN); integrated HIVprevention strategies (HPTN); and adult HIV therapeutic strategies including HIV cure, management of non-infectious co-morbidities and infectious co-morbidities of viral hepatitis and tuberculosis (ACTG). The CTU iscomprised of five clinical research sites (CRSs) at institutions where the clinical trials are conducted. Theseinstitutions are Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham andWomen's Hospital, Fenway Health Center, and The Miriam Hospital. The CTU is led by three highlyexperienced principal investigators, Drs. Raphael Dolin, Kenneth Mayer and Daniel Kuritzkes, and includeshighly accomplished CRS leaders and collaborating investigators. The CTU functions as an integrated, highlycollaborative entity, which has centralized planning, resource allocation, decision-making and financialmanagement through an efficient administration plan. Decisions are driven by a rigorous evaluation processbased on established metrics of performance and robust communication among leadership and staff of theCTU and CRSs. Centralized resources of the CTU include a Clinical Research Laboratory (CRL), a ResearchPharmacy Coordinator (RPC), Data and Quality Management Plans, and a Community Engagement Core. TheCTU has diverse and accessible populations for study, representing communities most affected by HIV/AIDS,hepatitis C virus infection, and tuberculosis, and have well-grounded connections with the communities inwhich they are based. The CTU is well poised and experienced to carry out efficient, high quality clinical trialsto address major questions in HIV clinical research. Its leadership and administrative structure facilitates theconduct of studies which cross traditional network boundaries and that enables rapid responses to newscientific directions as they emerge.Under this Administrative Supplement application, The HBP CTU is responding to NIAID's Notice of SpecialInterest (NOSI) (NOT-AI-20-031) to address the need for research on Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19). NIAID is particularly interested inprojects focusing on viral natural history, pathogenicity, transmission, as well as projects developing/expandingmedical countermeasures and suitable animal models for pre-clinical testing of vaccines and therapeuticsagainst SARS-CoV-2/COVID-19. In order to address this urgent public health need, the NIAID-supportednetworks have been charged to serve as a focal point of sponsored trials in COVID-19 vaccines andmonoclonal antibodies (mAbs) for preventing the acquisition of SARS-CoV-2, as well as to increaseunderstanding of and to establish treatments for COVID-19.The HBP CTU and its affiliated CRSs have well established and highly productive relationships with the NIAID-supported networks. Through its existing leadership and administrative structure, the HBP CTU is activatedand prepared to immediately support these efforts.The HBP CTU is based in Boston, Massachusetts, which has been a ""hot spot"" for SARS-CoV-2 infections andCOVID-19 cases. The HBP CTU is well poised and experienced to support these emerging research needsand interests. In particular, HBP CTU is prepared to support and implement studies needed for expandedSARS-CoV-2 RNA and serology testing at our affiliated Clinical Research Sites (CRSs). The CTU is alsoprepared to rapidly implement other studies related to NIAID's charge to address all aspects of SARS-CoV-2and COVID-19 research, vaccine development and clinical trials, other prevention measures, and potentialtreatments. Studies at the CTU may include: seroepidemiology of SARS-CoV-2 in the Boston/New Englandarea; treatment of COVID-19 with antivirals such as remdesivir and hydroxychloroquine; treament of advancedcases of COVID-19 with anti-IL-6 inhibitors; the conduct of clinical trials of candidate vaccines and mAbs forprevention and/or treatment of disease; and the development of in vitro assays used for making measurementsof SARS-CoV-2 neutralization, which have the ability to distinguish incremental advances in potency, breadth,and durability. The HBP CTU administration will oversee the expansion and implementation of these activitiesat our affiliated CRSs and Clinical Research Laboratories (CRLs).",2020,2020,BETH ISRAEL DEACONESS MEDICAL CENTER,900000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +C03816,unknown,Novel nanobodies to prevent and treat SARS-CoV-2 and other pathogenic human coronaviruses,"SummaryA novel coronavirus (CoV), SARS-CoV-2, is causing global pandemics with growing numbers of daily casesand deaths. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2002-2003 SARS epidemic, andless closely related to MERS-CoV, which causes a high mortality rate in infected patients. No therapeuticagents or vaccines have been approved to control the infections of these CoVs in humans, calling forimmediate efforts to develop effective countermeasures. The CoV spike (S) proteins are important targets fortherapeutics. They guide virus entry into host cells by binding to a host receptor through their S1 subunits andfusing the viral and host cell membranes through their S2 subunits. The S1 subunits contain a receptor-bindingdomain (RBD). Both RBD and S2 region of S protein can elicit neutralizing antibodies. The RBD is the majortarget to induce potent neutralizing antibodies, but it diverges among different CoVs, whereas the S2 region ofS protein is more conserved among different CoVs. Nanobodies (Nbs) are single-domain antibodies derivedfrom camelid antibodies. They are emerging as novel therapeutic agents, numbers of which have beenapproved or tested in clinical trials to prevent and treat other human diseases. Nbs possess many uniqueadvantages as therapeutic agents: they have high physical and chemical stabilities, excellent tissuepenetration capability (superior pharmacokinetics), easy expression with great production yields, androbustness for storage and transportation. Moreover, Nbs can potentially recognize epitopes (e.g. hidden orpartially hidden epitopes) that are not accessible to conventional antibodies. In this proposal, we will designand develop Nbs as therapeutic agents against SARS-CoV-2 and other pathogenic human CoVs using phagedisplay and structural biology as guiding tools. We propose to develop highly efficacious Nbs against SARS-CoV-2 to stop the current COVID-19 pandemic and also broad-spectrum neutralizing Nbs targeting future CoVinfections. We have established Nb libraries and identified several neutralizing Nbs targeting the RBDs ofSARS-CoV and MERS-CoV, providing a solid foundation for the proposed studies. In our previous work, weextensively characterized the structures and functions of MERS-CoV and SARS-CoV S proteins, and we haverecently characterized the RBD of SARS-CoV-2 and solved its structure in complex with viral receptor, pavingthe way for rapid screening and identification of SARS-CoV-2 S protein-based Nbs. The specific aims of thisproposal are to: 1) develop highly efficacious Nbs targeting SARS-CoV-2 S (RBD/S2) protein; develop broad-spectrum Nbs against CoV infections, 2) characterize these CoV S-targeting Nbs, and 3) evaluate in vivoefficacy of these Nbs against SARS-CoV-2 and other CoV infections. Overall, this proposal will develophighly efficacious Nbs targeting SARS-CoV-2 S protein, aiming to stop the current COVID-19 pandemic. It willalso develop broad-spectrum Nbs targeting future CoV infections. This proposal has important implications forcombating pathogenic coronaviruses and neutralizing their threat to human health.",2020,2025,NEW YORK BLOOD CENTER,832650,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03817,unknown,Structured nonparametric methods for mixtures of exposures,"The parent R01 focuses on developing reliable and interpretable statistical methods for theassessment of simultaneous health effects of multiple chemicals. This is challenging due to thestatistical curse of dimensionality, to moderate to high correlation in levels of exposure todifferent chemicals, and to missing data and limit of detection issues. Current statisticalmethods for nonparametric regression fail to adequately address these challenges, and canproduce uninterpretable dose response surfaces and high error rates in detecting interactions.The parent R01 is developing transformative methods that incorporate mechanistic constraintson response surfaces, allow for the complications inherent in epidemiology studies of mixtures,produce interpretable results including for interactions, and borrow information across differentdata sources. This R01 has already produced new statistical tools that clearly improve upon thestate-of-the-art, and that can be implemented routinely by epidemiologists using publicly-available software packages (e.g., Ferrari and Dunson, 2020a,b).This proposal describes a competitive revision of the parent R01 to provide a transformativestatistical toolbox for epidemiologists studying risk factors for COVID-19 infection,morbidity and mortality. This toolbox builds on the Bayesian modeling frameworks developedby the parent R01, while crucially accounting for the types of large spatially and temporallystructured datasets that are now being collected as part of the COVID-19 monitoring effort. Anew class of computational algorithms is proposed for rapid analysis of massive andcomplex spatial-temporal data, these algorithms are used to develop statistical tools forepidemiologists studying COVID-19 including an R package, and the approach is applied tostudy interactions between environmental exposures, age, and other comorbidities withCOVID-19 mortality.",2020,2022,DUKE UNIVERSITY,438776,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2018 +C03818,unknown,Vaccine and Treatment Evaluation Units (VTEU),"ABSTRACTThis supplement request is for a Phase 3, randomized, stratified, observer-blind, placebo-controlled study to evaluate the efficacy, safety and immunogenicity, of mRNA-1273 vaccinecompared to placebo in adults 18 years of age and older who have no known history of SARS-CoV-2 infection but whose locations or circumstances put them at appreciable risk of acquiringCOVID-19 and/or SARS-CoV-2 infection. This request also relates to other COVID 19 activities.",2020,2022,BAYLOR COLLEGE OF MEDICINE,5921655,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C03819,unknown,FeverPhone: Point of Care Diagnosis of Acute Febrile Illness using a Mobile Device,"Project SummaryIn this work, we will develop ""RAPID COVIDX"", a rapid screening technology for COVID-19 based onsimultaneous detection of SARS-CoV-2 antigen (Ag) and antibodies to SARS-CoV-2 virus (IgG/IgM) in humanblood and/or nasal/throat swab specimens within 15 minutes at the point of care (POC). This will leverage theNIH-funded FeverPhone platform, which we have already shown capable of rapidly quantifying both antigensand antibodies at the POC for several infections, including malaria (pLDH and HRP2) and dengue/chikungunyavirus infection (IgG/IgM). The 'RAPID COVIDx' technology builds on our team's extensive background in thedevelopment of smartphone-based diagnostics, infectious disease, and global health. The technical effort of thisprogram comprises of the development of in vitro immunochromatographic one-step assay to simultaneouslydetect SARS-CoV-2 specific IgG/IgM antibodies and antigens, a low-cost portable test strip reader for imagingthe test strips, and a mobile app to provide step-by-step instructions to the user. By the end of this project, wewill have developed a ""sample-in, answer-out"" working prototype that will be ready for further validation witharchived serum samples and for testing deployment readiness in POC settings. Serological tests such as theone proposed are going to be increasingly needed with the spread of the pandemic to both identify those withinfection but also those with past exposure. Further, this will be critical to determine those who can return to workand those who are vulnerable and direct limited resources. Key assets of our platform include minimal needs forinfrastructure, training, and sample volume. Additionally, the same platform works for multiple diseases/infectionsand can be commercialized at very low price points for both the reader and test strips. Last but not least, the PIsalso have started a company commercializing similar technology for nutritional tests; there is capacity investedby the New York State and the Department of Defense at this startup to scale up manufacturing of these testsand are also familiar with the licensing process to engage other partners for rapid commercialization.",2020,2021,CORNELL UNIVERSITY,377992,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03820,unknown,CHARACTERIZATION OF INNATE AND ADAPTIVE IMMUNE RESPONSES INDUCED BY DIFFERENT HUMAN CORONAVIRUSES IN HUMAN PRIMARY SYSTEMS,"ABSTRACTThrough comparative analysis, different coronaviruses, including the novel SARS-CoV-2 andhuman seasonal coronaviruses hCoV-OC43 and hCoV-NL63 will be used to unveil both theirsimilarities and differences in cellular susceptibility and permissiveness, innate immuneresponses, and immune modulatory potential in primary human cell systems including monocytederived dendritic cells (MDDCs), normal human bronchial epithelial cells (NHBEs), and an exvivo tonsil histoculture (HC) system. We will use state of the art techniques to analyze toseresponses intracellularly and extracellularly. Our group specializes in the manipulation ofprimary human cell systems and investigating both innate immune responses to viral infectionas well as viral antagonism of innate immune sensing. As such we are uniquely positioned torespond to this new public health threat and provide critical information regarding the molecularbiology of SARS-CoV-2.",2020,2021,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,423750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03821,unknown,In vivo PET imaging of novel engineered AAVs informs capsid design,"Abstract of: Proposed COVID-19-related supplement to In vivo PET imaging of novel engineered AAVs informs capsid designThere is an urgent need to develop tools to assess viral pathogenesis and the efficacy of potential therapeuticsfor novel viruses such as SARS-CoV-2. While organoid and cell-based assays have been broadly used toassess the candidate receptor of such viruses, these assays cannot answer key questions as to: 1) whethermultiple receptors for the virus exist, 2) the in vivo receptor affinity of the virus and accumulation within theupper respiratory tract, 3) transport of the virus into the vascular system and ultimately to the heart andkidneys, and 4) the resulting transfection of these various sites. Our laboratory has previous developedmethods to label adeno-associated viruses and track their transport following systemic injection. We foundthat these engineered viruses carry cargo attached to the capsid across the blood brain barrier and the cargoaccumulates deep within the brain. Combined optical and PET studies have suggested that binding of thevirus to its receptor results in transcytosis of the intact capsid. We hypothesize that coronaviruses maypossess similar capabilities to be transported across the lung epithelium. We plan to address key issues byassessing receptor binding and transduction using PET and optical imaging. Our resulting specific aims are thefollowing: 1) development and validation of tagging strategies to image pseudotype viral particles at BSL2, 2)development and validation of reporter gene strategies to image transduction of engineered viruses, and 3)application and dissemination of these dual strategies to assess viral transport, transduction and susceptibilityto available therapies including a) antibodies, b) protease inhibitors, and c) fusion inhibitors. We propose to develop and image engineered viruses expressing the spike protein and a reporter gene and track theseviruses within a model of lung fibrosis and a mouse model with a humanized ACE2 receptor. We will leveragethe capabilities to label and track viral capsids and transduction developed within this R01 and key capabilitiesof Stanford University. Pseudotype viruses based on vesicular stomatitis virus (VSV) and lentivirus have beendeveloped with spike proteins corresponding to SARS-CoV or SARS-CoV2. Further, replicons with intact viralproteases have been engineered. We propose to collaborate with those developing and testing engineeredviruses and therapeutics at Stanford, including Jan Carette and Catherine Blish in addition to the key personnelon our parent project. At the conclusion of each phase of this project, we will disseminate strategies for theincorporation of a PET tag, a reporter gene, and dual PET imaging protocols. We hypothesize that these toolscan be disseminated and rapidly modified to assess both SARS-CoV-2 and future viruses. We will make ourtechnology available through commercial and scientific partners.",2020,2023,STANFORD UNIVERSITY,655422,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2019 +C03822,unknown,Covid-related changes in Taste Epithelium,"PROJECT SUMMARYDisruption of the sense of taste is a common feature of COVID-19. The proposed supplement will investigatepotential histopathological changes in taste buds and the surrounding epithelium of the tongue in patients whohave lost their sense of taste during COVID-19. Biopsies of fungiform papillae will be obtained from a tastecenter in Germany which shall conduct psychophysical testing prior to sampling 4 fungiform papillae frompatients recovering from COVID-19 - either with or without taste loss. We will analyze these samplesmolecularly and histologically to test for presence of residual virus and for changes in taste bud number,morphology or cellular composition.",2020,2021,University of Colorado Denver,191384,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas | Europe,Data Management and Data Sharing,,,United States of America,United States of America | Germany,Clinical characterisation and management,Disease pathogenesis,2020 +C03823,unknown,"The perception of odor blends and mixtures: Modulation, Inhibition and Enhancement of Olfactory Receptors alters perception of complex blends","Project Summary/AbstractThis application seeks to take advantage of a unique opportunity to obtain significant amounts of human nasal tissue form recent CV-19 positive post mortems. Working with the Columbia University Medical Center Pathology Department and an ENY surgeon tissue is being recovered from post mortem procedures performed within 24 hours of death. We currently have 20 tissue samples of OE (attached to cribiform plate) and OB, in fixative and refrigerated or flash frozen. At the outset of the pandemic spread of the virus there were initially anecdotal, but now well quantified, reports of sudden anosmia and dysgeusia (likely a result of the anosmia) appearing 2-4 days before onset of the documented respiratory and fever symptoms of CV19. Although not all cases of CV19 experience the anosmia, all anosmias eventually became positive for CV19. The sense of smell is reportedly recovered in all surviving patients but requires 4-6 weeks post infection, long after other viral symptoms have resolved. The appearance of anosmia in the absence of respiratory symptoms - both before and after the disease time course, is of special interest as it differs significantly from hyposmias experienced during other respiratory illnesses. We will utilize human post mortem tissue to investigate, with advanced microscopy techniques and tissue preparation, several possible causes for this mysterious anosmia - including cell loss, tissue degeneration, cilia loss, vascular abnormalities, immune response comorbidities, and direct viral infection.",2020,2024,Columbia University,202500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2014 +C03824,unknown,The Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU),"SARS-CoV-2 is a coronavirus that has emerged as a major cause of pandemic upper and lowerrespiratory tract infection, progressing in approximately 15-20% of infected persons to severepneumonia that can be complicated by adult respiratory distress syndrome (ARDS) and, in 1-3% of infected persons, death. Collectively, respiratory and systemic illness due to this virus isreferred to as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infection also manifestswith relatively mild symptoms such as cough, sore throat, and fever, or with no symptoms(asymptomatic infection). Persons with a mild or asymptomatic infection have been implicatedin the spread of this highly infectious virus in the community. Efficient, safe, and rigorousresearch and clinical trials are essential to the development of interventions that can treat andprevent COVID-19 infection. The Baltimore-Washington-India Clinical Trials Unit (BWI CTU)supports high quality HIV-related treatment and prevention research at two domestic ClinicalResearch Sites (CRS's) in Baltimore and Washington. The Johns Hopkins University ClinicalResearch Site (JHU CRS) in Baltimore, and the Whitman Walker Health (WWH) CRS inWashington, DC, have highly experienced and innovative leaders in anti-infective research andhave a long and successful record of HIV and viral hepatitis clinical research implementation.The health systems that are supported by JHU and our partner institutions currently providemedical coverage for more than half of all adult residents in the state. This includes having aphysical presence in every major population center in the state, including the metropolitanWashington, DC, counties -- where nearly half of the state's cases have occurred. This gives usunprecedented access to those with or at risk of this infection. JHU is also home to the Centerfor Immunization Research, a renowned resource for clinical vaccine development andevaluation. We have been invited by the HPTN and HVTN to serve as a site for SARS-CoV-2vaccine and monoclonal antibody prevention trials. COVID-19 clinical research provides specialchallenges beyond the processes developed for most traditional infectious diseases clinicalresearch. This supplement will allow our sites to prepare to offer high quality COVID-relatedclinical research sponsored by DAIDS Networks, and enhance the protection of investigatorsand research participants at JHU and WWH.",2020,2020,JOHNS HOPKINS UNIVERSITY,460679,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +C03825,unknown,"Accelerating viral outbreak detection in US cities using mechanistic models, machine learning and diverse geospatial data","ABSTRACTSince early January 2020, our interdisciplinary research team has conducted several studies to elucidate theemerging threat of COVID-19 and support public health responses throughout the United States, resulting inpeer-reviewed publications, online COVID-19 forecasting tools, and extensive engagement with city, state and national decision makers. In our collaboration with the CDC to develop a national modeling resource for pandemic preparedness, we had recently developed a national model for evaluating multi-layered intervention strategies to contain and mitigate outbreaks in US cities. We adapted the model to COVID-19 by incorporating the latest estimates for age- and risk-group specific rates of transmission, disease progression, asymptomatic infections, and severity (including risks of hospitalization, critical care, ventilation and death). The model is designed to flexibly incorporate combinations of social distancing, contact tracing-isolation, antiviral prophylaxis and treatment, as well as vaccination strategies. Our Supplementary Aims propose to build a more granular and data-driven model of COVID-19 to elucidate the transmission, identify high-risk populations, surveillance targets and effective control of this and future epidemics within US cities. Aim S1: Focusing initially on the Austin-Round Rock metropolitan area in Texas,we will apply these models to improve real-time risk assessments and optimize the timing and extent of layeredsocial distancing measures. Aim S2: We will rapidly evaluate strategies for rolling out antiviral prophylaxis and therapy based on clinical trial data. Aim S3: We will develop user interfaces for our Austin and national modelsto support both scientific research and public health efforts to mitigate COVID-19 and plan for future pandemicthreats. These Aims are synergistic with Specific Aim 2 of our parent grant (R01 AI151176-01), in which we aredeveloping high-resolution models of viral transmission to improve the early detection and control ofanomalous respiratory viruses, particularly in at risk populations.",2020,2023,YALE UNIVERSITY,387199,Human Populations | Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C03826,unknown,Evaluation of the Interplay between HIV and COVID-19 in a large urban safety-net HIV clinic,"PROJECT SUMMARY/ ABSTRACT An unprecedented public health emergency due to the COVID-19 pandemic is unfolding worldwide and the United States has been the epicenter of the pandemic since March 26, 2020. No prior global pandemic ofthis scale has overlapped temporally with the HIV pandemic. Despite this, given the breathtaking speed atwhich the pandemic has progressed, very little is known about the interplay between HIV and SARS-CoV-2 given that COVID-19 has only recently entered areas of high HIV prevalence. The COVID-19 pandemic isthreatening worldwide gains in UNAIDS 90:90:90 targets for HIV by disrupting health systems, economies, andthe health of people with HIV. San Francisco was the first city in the U.S. to impose ""shelter in place""public health measures on March 16, 2020. Given the need to limit in-person visits to counter the spread ofCOVID-19, research on the impact on HIV outcomes, retention in care, and socio behavioral outcomes will becrucial to develop interventions to attenuate COVID-19's deleterious impact and to plan for future pandemics. Whether people with HIV (PWH) are more or less susceptible to COVID-19 or severe disease is unknown;some of the risk factors for severe COVID-19 (older age, cardiovascular disease, pulmonary disease) are more prevalent among PWH but HIV medications such as tenofovir and its metabolites could be protective. PWH inlow-income settings have marginal housing and food insecurity, increasing transmission risk. Given the impactof HIV on immune responses, it is also important to understand if PWH will have less durable immunity against COVID-19 following infection. Finally, the impact of the COVID-19's disruption of medical and social services for PWH needs urgent study, both during the crisis and in its aftermath, since COVID-19 has the potential toeradicate the progress made on Ending the HIV Epidemic to date. This proposal will answer three vital questions concerning the interplay between the two viruses. The site of the study will be at the Ward 86 HIV Clinic, a large safety-net clinic for publicly-insured patients with HIV in San Francisco, near the neighborhoods experiencing concentrated COVID-19 epidemics. Aim 1 will provide novel, urgently needed insights into how SARS-CoV-2 infection risk, prevalence and clinical outcomes vary by HIV status and/or antiretroviral regimen (i.e. tenofovir). Aim 2 will explore whether HIV infection will impair humoral or T-cell responses to COVID-19, providing insights for therapeutic and vaccine development. Aim 3 data will evaluate the impact of disruption of healthcare and social support systems on PWH, including viral suppression; retention in care; hospitalizations, co-morbidity outcomes, and non-COVID-19 related death; healthcare utilization during COVID019; and socio-behavioral outcomes during and after social distancing toassess isolation, food insecurity, stress, substance use, stigma, and resilience. Harnessing, the researchinfrastructure of the UCFAR, city wide COVID-19 registries, and a large, aging population of PWH served by the Ward 86 clinic, this grant will put immediate, high-impact studies in place to track the colliding pandemics.",2020,2024,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,709784,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C03827,unknown,COORDINATING CENTER TO HELP ELIMINATE/REDUCE ORAL HEALTH INEQUALITIES IN CHILDREN,"U01 Project Summary/AbstractCoronavirus Disease 2019 (COVID-19) is a pandemic currently without preventive or curative treatments,causing unprecedented disruption and costs to individuals and society. This COVID-19 Administrative Supplement to the ""Coordinating Center to Help Eliminate/Reduce Oral Health Inequalities in Children"" (CC)(U01DE025507) will leverage collaborative research and coordinating center expertise and services to aUniversity of California Office of the President (UCOP) reviewed and California Breast Cancer ResearchProgram funded (R00RG2901) pilot trial to assess antiseptic mouthwashes in SARS-CoV-2 infected adults on viral load. Initial guidance from US Centers for Disease Control and Prevention and American Dental Association recommended dental providers have patients use a pre-procedural antiseptic rinse, despite no empirical clinical evidence. This proposed administrative supplement will specifically address the item in NOT-DE-20-022 ""Pilot testing of existing therapeutic modulators of oral microbiota that may limit infectivity of SARS-CoV-2"". The CC team possesses relevant transdisciplinary expertise in clinical trials, epidemiology, biostatistics, clinical research, and oral health, as well as data coordinating center experience serving multiple health and oral health projects in NIH research consortia. As the NIDCR Oral Health Disparities in Children(OHDC) Consortium's Coordinating Center the team has demonstrated its ability to collaboratively and creatively support large-scale, clinically-relevant, prevention trial research simultaneously in 9 UH2 studies and then in 4 UH3 randomized clinical trials in 6 institutions across 3 time zones to meet the overall scientific and project community partner goals. The CC will establish ongoing, collaborative relationships with the pilotproject team to provide services and expertise in the following areas: (a) oral health-related clinical knowledge; (b) quantitative research design with particular emphasis on health outcomes in diverse populations; (c)selecting, developing, and refining measurement instruments; (d) informatics, including providing secure,customized data acquisition systems and project management and clinical trials management systems; (e)training in the use of those systems; (f) participant safety monitoring and reporting to the project investigators; (g) data management, processing, and quality control; (h) refining quantitative data analysis plans; (i) reportingon trial progress to the project investigators; and (j) perform statistical analyses including sample sizeestimation for any follow-up trials. Our experienced Coordinating Center team can provide efficient,comprehensive support to this UCOP funded pilot trial which could provide critical knowledge to form theempirical foundation to develop strategies to potentially benefit health care workers, frontline workers, high riskindividuals such as immunocompromised people (including breast cancer patients), and groups impacted byhealth disparities.",2020,2021,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,242250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C03828,unknown,Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1,"Abstract COVID-19, caused by the coronavirus SARS-CoV-2, has an unpredictable clinical course ranging froman asymptomatic carrier state to severe acute respiratory syndrome (SARS). The vast majority of young individuals have an asymptomatic to moderate clinical course, but a subset of patients develop a severe systemic inflammatory response. The genetic factors regulating the immune response to SARS-CoV-2 remain undefined. Our preliminary data shows that since Boston Children's Hospital began admitting patients with COVID-19 in late March 2020, eight of nine of patients with severe COVID-19 had pre-existing lymphopenia, autoimmunity, or hypogammaglobulinemia. None of four patients with moderate COVID-19 had prior history ofimmune dysfunction. Whole exome sequencing on one of the patients with severe COVID-19 and extremely elevated soluble CD25 levels identified a heterozygous frameshift mutation (p.Ala9Profs) in SOCS1, encodingSuppressor of Cytokine Signaling 1. The mutation is predicted to result in SOCS1 haploinsufficiency, whichresults in overactivation of T cells in SOCS1 haploinsufficient mouse models. SARS-CoV-2 may induce endoplasmic reticulum (ER) stress through multiple pathways. Several viralproteins bind to ER resident proteins and to COPI, the heptameric complex that mediates retrograde proteintrafficking from the Golgi to the ER, potentially causing ER stress. Massive cytokine secretion induces ERstress by increasing the load of nascent proteins in the ER, and cellular exposure to high levels of circulatingcytokines further increases ER stress. Notably, the clinical phenotype of severe COVID-19 parallels thatobserved in COPG1 mutant mice during polymicrobial infection, resulting in increased ER stress in activatedlymphocytes. We hypothesize that young individuals with severe COVID-19 exhibit a dysregulated immune response to SARS-CoV-2 infection, characterized by increased ER stress and reduced lymphocyte survival. In AIM I we will test the hypothesis that children with severe COVID-19 have deleterious variants ingenes regulating the equilibrium between anti-viral immunity and immune homeostasis. In AIM II we will test the hypothesis that ER stress contributes to the T cell lymphopenia characteristic of severe COVID-19 and can be reversed with administration of TUDCA. The proposed studies have the potential for identification of genetic variants underlying severe COVID-19,and thereby pathways important for disease severity. In parallel, our investigations of ER stress in immune cellsfrom patients with COVID-19 will test the hypothesis that readily available ER stress relieving agents may be useful for the treatment of COVID-19.",2020,2022,BOSTON CHILDREN'S HOSPITAL,389802,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C03829,unknown,Antibody repertoire characterization in the context of coronaviruses,"Project Summary. SARS-CoV-2, or the 2019 novel coronavirus, is a significant pandemic threat that has resulted in hundreds of thousands of diagnosed cases and tens of thousands of mortalities as of March 2020.The development of preventive and therapeutic measures that can counteract the ongoing, and any future,coronavirus pandemics is therefore of utmost significance for public health worldwide. The S protein is the immunodominant region of coronaviruses (CoV) recognized by the immune system and serves as the target for a number of neutralizing antibodies. Passive transfer of neutralizing antibodies has been shown to prevent coronavirus infection in animal models. Further, engineered prefusion-stabilized S protein immunogens have been shown to elicit high titers of coronavirus-neutralizing antibodies in animal models, in the context of MERS.Together, this prior work establishes a strong premise for targeting the identification and characterization of neutralizing antibodies in the context of SARS-CoV-2. More generally, a better understanding of the human antibody response to the S protein of SARS-CoV-2 as well as other related CoV members can help inform therapeutic antibody optimization and accelerate vaccine design efforts. Our laboratory recently developed the LIBRA-seq technology (LInking B-cell Receptor to Antigen specificity through sequencing) for antibody discovery and characterization of antigen-specific antibody repertoires. Unlike other B cell approaches, LIBRA-seq is the first to enable the simultaneous determination ofBCR sequence and antigen specificity for a large number of B cells against a theoretically unlimited number of diverse antigens, at the single-cell level. LIBRA-seq therefore provides a unique opportunity for characterizing the types and specificities of antibodies that can recognize the S protein from SARS-CoV-2, as well as otherCoV viruses. Here, we propose to utilize the LIBRA-seq technology in the context of SARS-CoV-2, with two major goals: (1) To identify cross-reactive antibodies that recognize multiple antigen variants associated with human coronavirus infection, including SARS-CoV-2, SARS-CoV-1, and MERS-CoV, and (2) To evaluate the ability of current lead CoV vaccine candidates to engage with antibody repertoires from healthy individuals. Taken together, the efforts proposed in this application will be of high potential translational/clinical impact for SARS-CoV-2 and other CoV pathogens of biomedical significance. The types of antibody repertoire characterization that we propose to develop here will also be readily generalizable to other pathogens, and as such, will have a broad and lasting impact on the development of counter measures for established and emerging infectious diseases.",2020,2022,Vanderbilt University Medical Center,666819,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +C03830,unknown,Identifying Coronavirus B-cell Epitopes Associated with COVID-19 Illness Severity,"Identifying Coronavirus B-cell Epitopes Associated with COVID-19 Infection and Illness The new coronavirus outbreak that begin in December 2019 has created a global public health emergency. Thishas led to an intense search to identify factors that contribute to the susceptibility and severity of illness. Werecently developed an array to identify antibody-binding epitopes for rhinoviruses. Data from these arrays can be combined with information about viral protein structure to identify highly immunogenic regions for respiratory viruses. We propose to expand this array to include linear epitopes that represent the entire proteome of SARS-CoV-2 and all other common coronaviruses that infect humans (OC43, NL63, etc.). The study population will include children from the COAST, WISC and URECA birth cohort studies who are also participating in the HEROS SARS-CoV-2 surveillance study. As part of routine cohort activities, these children undergo serial sampling of blood and nasal secretions that we can analyze using the array to determine individual patterns ofantiviral antibody epitope recognition. We hypothesize that the pattern and quantity of antibody specific for epitopes of common coronaviruses contributes to the susceptibility to SARS-CoV-2 infection and illness. We propose three specific aims that will utilize sera obtained from children before and after HEROS-confirmed infection with SARS-CoV-2. First, in specimens obtained pre-infection we will use the array to identify patterns of antibody epitope recognition to common childhood coronaviruses, assess cross-reactivity with SARS-CoV-2,and determine whether cross-reactivity is associated with protection against infection or illness. In the second aim, we will determine whether the diversity of antibody responses to common respiratory viruses is associated with a reduced risk of infection or illness. Finally, in the third aim we will describe antibody binding patterns before and after known COVID-19 cases to identify candidate regions that are immunogenic and neutralizing. To accomplish this aim, we will perform micro-neutralization assays (available in the BSL3 laboratory of Dr. KristenBernard, UW Madison) on convalescent sera or nasal secretions from children who developed symptomatic infection. This information will be analyzed together with pre- and post-infection array data using machine learning approaches to identify neutralizing epitopes. Identifying patterns of serologic responses that are cross-protective could help to identify susceptible individuals in the population and direct the design of vaccines tocurrent and future viruses.",2020,2023,UNIVERSITY OF WISCONSIN-MADISON,406048,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03831,unknown,HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals,"This proposal outlines the scientific agenda for the Leadership and Operations Center of the HIV VaccineTrials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4 continents dedicated to developing globally effective vaccines for HIV, tuberculosis and now SARS-CoV-2.The HVTN has led HIV prevention science for over 20 years through robust phase 1 and 2 clinicaldevelopment trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizing monoclonal antibody (mAb) VRC01 undergoing testing in 5 randomized controlled efficacy trials.With the rapid onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in thefield on the contribution of immune functions involved in preventing infection, in modifying COVID-19 disease,and in clearing viral infection. We believe the HVTN is well placed to study these gaps and rapidly deploy this information in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study we propose initiating an observational cohort study of approximately 400 persons in the United States (22 trialssites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a variety of risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adults between 18 and 55 years of age and those older than 55 years, and persons with high interest clinical or virologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolonged viral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims ofthis study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, to develop and qualify a suite of immunologic assays and reference reagents that will permit detailed interrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in key populations and risk groups, and to characterize presentations of the infection among convalescent individuals. This initial study will tell us much about the adaptive immune responses in persons who have been infected and recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfully clearance of infection. It will improve our understanding of the dynamics and duration of responses, as well as the epitope specificity and other defining signatures, and will inform rational design and testing of preventive and therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork for prospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study will prepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.Laboratory, statistical and operational experience in this first trial will be invaluable preparation and priming ofnetwork machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVID Prevention Network in coming months.",2020,2020,FRED HUTCHINSON CANCER RESEARCH CENTER,401609,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America | Peru,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C03832,unknown,Exploring COVID-19’s Impact on the Care and Well-being of Community Dwelling Persons with Dementia,"AbstractThe disease, COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)was first identified in Wuhan, China. As the COVID-19 pandemic continues to spread throughout the UnitedStates, it puts exceptional burden on at-risk vulnerable populations, including people with Alzheimer's andrelated dementias (hereafter dementia) and their informal and formal support systems. Per the Centers forDisease Control & Prevention, implementation of social distancing (""remaining out of congregate settings,avoiding gathering, maintaining distance approximately 6 ft from others"") is an essential public health practiceto reduce transmission of COVID-19 and a key strategy to guard at-risk populations (e.g., persons withdementia). Community-dwelling live-alone persons with dementia often require ongoing in-person informal(e.g., family or friends) and formal (e.g., home-based care providers) support to successfully engage in variousinstrumental activities of daily living. However, given present social distancing guidelines, this necessary in-person support is likely stymied. How social distancing impacts the execution and receipt/acceptance ofinformal/formal care remains unstudied. The supplement addresses these knowledge gaps by exploring howlive-alone persons with dementia and their informal and formal supports navigate and negotiate socialdistancing guidelines. Leveraging the large recruitment databases from the parent study, Aging at Home Alonewith Alzheimer's and Related Dementias, we propose to conduct an ancillary multi-perspective exploration(N=41) with key informal and formal care providers of live-alone persons with dementia. Together with expertsin the field of dementia and communicable diseases, the parent study's theoretically driven interview guide hasbeen modified to be disease-specific (COVID-19). This ancillary data collection offers a unique andcomprehensive strategy to explore the complex and important perspectives of informal and formal careproviders addressing three specific aims: 1. Explore how social distancing impacts the care & well-being oflive-alone persons with dementia and their informal caregivers; 2. Identify how formal support providers, whoserve community-dwelling persons with dementia, navigate social distancing requirements and its impact onpatient care; 3. Explore informal and formal care providers' perspectives of discrimination and stigmatization.The proposed supplement will address each specific aim using code-based analysis in ATLAS.ti. The proposedresearch offers an effective and immediate ancillary data collection strategy, rarely available within time-intensive qualitative inquiry, to address a complex and vital public health concern. Findings will provide acomprehensive understanding of how live-alone persons with dementia and their carers approach, prioritize,and/or withdraw from various care provisions. Knowing the ""how"" will provide data necessary to developcontextually appropriate care and support plans during critical public health crises that require physicaldistancing for prolonged periods.",2020,2021,UNIVERSITY OF MARYLAND BALT CO CAMPUS,163856,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2019 +C03833,unknown,Flu Dynamics COVID-19 Supplement,"PROJECT SUMMARY/ABSTRACTSARS-COV-2, the virus that causes Coronavirus Disease (COVID) emerged in China in late 2019. It rapidlyspread worldwide and is now causing a pandemic with high morbidity and mortality. Because SARS-COV-2 isa novel virus in humans, there are many fundamental knowledge gaps in our understanding of the virus anddisease. To undertake a detailed investigation of SARS-COV-2 in Nicaragua, we propose to add onSARS-COV-2 aims to our existing Household Influenza Cohort Study. The research questions addressed build naturally on the infrastructure currently in place to conduct the Household Cohort Study. Specifically, wewill add SARS-COV-2 testing on to samples that are already collected through our ongoing cohort study, addthe collection of blood samples around SARS-COV-2 infection in participants, and perform a household SARS-COV-2 transmission study. This proposal addresses major gaps in knowledge on COVID natural historyand transmission. It is thus timely and well-poised to have substantial public health and scientificimpact.",2020,2021,UNIVERSITY OF MICHIGAN AT ANN ARBOR,364096,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,Nicaragua,Nicaragua,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease transmission dynamics",2020 +C03834,unknown,Computational models of naturally acquired immunity to falciparum malaria,"ABSTRACTSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has spreadrapidly across the globe and caused unprecedented global health and economic threats. Emerging evidencesuggests that SARS-CoV-2 infection is associated with an impaired Type I and Type III interferon response,and that this reduced response may play a critical role in immunopathogenesis. Our collaboration has recentlybegun a randomized clinical trial of a Type III interferon, pegylated-lambda interferon (Lambda) for treatment ofSARS-CoV-2 infected patients at Stanford University. In the parent study, 120 SARS-CoV-2 infected patients(both symptomatic and asymptomatic) are being randomized to receive Lambda vs. placebo, withassessments for viral shedding in oropharyngeal and nasal swabs, daily symptom screening for 28 daysfollowing treatment, and peripheral blood collected at multiple timepoints, including 4, 7, and 10 months post-infection. In this proposal, we will leverage samples collected from this trial, comprehensive immunologicinterrogation, and computational analysis to elucidate the dynamics of the host immune response to SARS-CoV-2. In Aim 1, we will determine whether specific immune features, including endogenous IFN-λ productionand cytokine production in response to toll-like receptor (TLR) ligands, predict duration of viral shedding and/orsymptoms in SARS-CoV-2 infected patients. We will also evaluate differences in immune trajectories based onthe presence or absence of clinical symptoms, participant sex, and age. We will broadly profile immuneresponses using parallel methodology to our U01, including transcriptional profiling, cellular phenotyping,plasma cytokine levels, antibody profiling and functional assays, and build flexible computational models tomodel interactions between different compartments of the immune system and to assess associations betweenimmune responses and virologic and clinical outcomes. In Aim 2, we will define the impact of Lambda on theadaptive immune response, including SARS-CoV-2 specific cellular and humoral immunity. We hypothesizethat treatment with Lambda reduces time to seroconversion and is associated with improved immunologicmemory to Lambda, including higher titers and duration of neutralizing antibodies and frequencies of Th2-typeT follicular helper cells. To perform these studies, we will leverage our computational immunology U01research team at Stanford and UCSF including experts in clinical trials and cellular immunity (Dr.Jagannathan), antibody profiling and function (Drs. Greenhouse and Wang), infectious diseases epidemiologyand biostatistics (Dr. Rodriguez-Barraquer), and biomedical informatics and computational biology (Dr. Butte).By improving our understanding of the host immune response to natural SARS-CoV2 infection, identifyingcorrelates of viral resolution, and analyzing the impact of a novel immunomodulatory drug on this immunity, ourresults will provide insight into mechanisms that can be exploited in the design of vaccines and othertherapeutics.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN FRANCISCO,591089,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03835,unknown,Chasing Covid Cohort,"Abstract Immediate characterization of the effects of non-pharmaceutical interventions (NPIs) on communitySARS/COV2 spread will be essential to safely re-opening the U.S. economy. We propose integration of rapidserologic assessment and extension of follow-up in an existing national cohort study of SARS/COV2, theCHASING COVID Cohort (C3) study. Launched on March 28th, 2020, we have already enrolled >4,700 adultparticipants from all 50 U.S. states and Puerto Rico into longitudinal follow-up (Figure), providing the opportunityfor rapid investigation of the effect of different NPIs on SARS/COV2 spread in the United States. With this newapplication for funding, we seek to expand on this work by adding rapid serologic testing and extendingfollow-up to address the following specific aims: 1. Estimate the cumulative incidence of SARS/COV2, and evaluate impact of different NPIs on the cumulative incidence of SARS/COV2 infection, COVID (disease), andCOVID deaths; 2. Estimate the proportion of persons with serologic evidence of SARS/COV2 infection who were asymptomatic or had only mild symptoms; 3. Assess whether SARS/COV2 antibodies are protective againstsubsequent COVID disease. We will conduct in-depth interviews with participants to help contextualize andinterpret key findings. To help increase the scientific impact of this project, we will post public use datasets onGitHub, along with software tools. By deploying specimen collection now, the rapid knowledge gained byaddressing the above aims will help inform policy and implementation and relaxing of NPIs, as well asmathematical models, in the US and around the world.",2020,2022,City University of New York,2653115,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America | United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control",Immunity | Impact/ effectiveness of control measures | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities,2020 +C03836,unknown,CC16 in Childhood and Resilience to Persistent Asthma into Adult Life (Supplement),"PROJECT SUMMARYIn response to NOT-AI-20-031 [""Notice of Special Interest: Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19)""] and in line with the scope of the parent grant, thegoal of this supplement is to determine the role of Club cell secretory protein (CC16) in providingresilience to COVID-19. CC16 is a homodimeric pneumoprotein that is encoded by the SCGB1A1 gene,mainly produced by Club cells in the distal airways, and readily measured in circulation.The central hypothesis of our parent grant is that CC16 exerts protective effects in the lungs by modulatingsusceptibility and inflammatory responses to airway infections. In addition, because CC16-secreting Club cellsare among the main airway cell types expressing Angiotensin-Converting Enzyme 2 (ACE2), it is plausible that- by infecting Club cells - SARS-CoV-2 can affect their survival and/or secretory machinery, and in turn impactproduction of CC16. Here, we postulate that CC16 plays a critical role in susceptibility and host inflammatoryresponses to SARS-CoV-2 and propose the following specific aim:Specific Aim - To determine the relation of circulating CC16 to the presence and clinical progression ofCOVID-19.In this pilot study, we will collect clinical data and biospecimens from both inpatients and outpatients withCOVID-19 at Banner University Medical Center - Tucson. Depending on the dynamics of the pandemic, weestimate that we will recruit between 75-125 inpatients and 100-200 outpatients. In addition, we will recruit agroup of controls (with a target case:control ratio of 2:1). Data from these participants will be used to comparecirculating levels of CC16 across the three groups of controls, COVID-19 outpatients, and COVID-19inpatients. In addition, circulating deficits of CC16 will be tested for prediction of subsequent clinicalprogression of disease.",2020,2021,UNIVERSITY OF ARIZONA,149165,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2020 +C03837,unknown,WCM-Rutgers NJMS CTU Supplement for COVID Testing,"ABSTRACTThe Rutgers New Jersey Medical School (NJMS) Clinical Research Site (CRS) 31786 isrequesting $300,000 in funding to help support Severe Acute Respiratory Distress SyndromeCoronavirus-2 (SARS-CoV-2) testing. The CRS is part of the Weill Cornell-Rutgers NJMSClinical Trials Unit and has been a site for two Division of AIDS (DAIDS) funded clinical trialsnetworks: AIDS Clinical Trials Group (ACTG) and HIV Prevention Trials Network (HPTN) forfifteen years.The program plans to provide SARS-CoV-2 testing by leveraging its existing relationships withthe local community and partnering with the clinical laboratory located at Public HealthResearch Institute (PHRI), also a Rutgers facility to perform SARS-CoV-2 testing using theCepheid testing platform. The Cepheid COVID-19 testing platform has been developed at PHRIwith Cepheid and is one of the most sensitive tests currently available to detect SARS-Co-V 2infection.We will provide SARS-CoV-2 testing at the CRS, in an adjacent building and on a mobile van.These testing locations are well-known and easily accessible to the community, healthcareworkers and other high-risk groups. We will also attempt to ensure that special populations suchas minorities and the LGBTQ community have access to the test. Finally, this will help the CRSfurther strengthen its relationship with the community and allow the unit to provide an essentialservice to this hard-hit community.If funded, this project will allow us to rapidly increase the availability of SARS CoV-2 testing andhelp contribute to the urgent need for additional COVID testing in an underserved communitylocated near the epicenter of the COVID-19 pandemic in the United States.",2020,2020,Weill Cornell Medicine - Cornell University,300000,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Health Personnel | Hospital personnel | Nurses and Nursing Staff,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,,,2020 +C03839,unknown,Florida Development in Early Childhood: Adversity and Drug Exposure (FL-DECADE) Study,"PROJECT SUMMARYIn this administrative supplement application, we propose to expand the original aims of ourFlorida Development in Early Childhood: Adversity and Drug Exposure (FL-DECADE) Study(R34DA050299) to accomplish NIDA research objectives related to the 2019 Novel Coronavirus(2019-nCoV, also known as COVID-19). As part of Phase I of the Healthy Brain and ChildDevelopment (HBCD) Study, the proposed activities of this supplement will provide additionalinformation related to the feasibility of a long-term cohort study of pregnant women and children(HBCD Phase II). COVID-19 will assuredly impact families through the planned enrollment periodof Phase II, thus the knowledge gained from the activities proposed in this administrativesupplement are critical to the early success of the Phase II cohort. Through this administrativesupplement, we will gain a broad understanding of stress and anxiety faced by pregnant andparenting women in Florida, and how their daily lives and prenatal care has changed during thepandemic. We will assess the feasibility of using a very large clinical data research network toidentify pregnant women who are COVID-19 positive in the event it is decided to target thispopulation for recruitment in Phase II. Finally, we will also test the feasibility of using innovativeways to remotely collect data from the home, which will be valuable in developing a long-termcohort study.",2020,2021,UNIVERSITY OF FLORIDA,189329,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts,2019 +C03840,unknown,Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative,"PROJECT SUMMARY/ABSTRACT:The HCSRN-OAICs AGING Initiative seeks an administrative supplement (PA-18-591/NOT-AG-20-022) toR33AG057806 to address pressing research questions related to prevention, control, management, andtreatment of COVID-19 in nursing homes, such as: What are the characteristics of the small to modest-sizedclusters of nursing homes that are associated with the AGING Initiative partners?; What COVID-19 relatedresearch questions, with direct applicability to the care and well-being of nursing home residents, would be ofthe highest priority and most amenable to study in the context of the ongoing pandemic?; What are the currentbarriers and challenges to conducting COVID-19 related research in nursing homes?; and What steps wouldbe required to create a nursing home clinical trials network comprised of the small to modest-sized clusters ofnursing homes that are associated with the AGING Initiative partners? The ""Advancing Geriatrics Infrastructureand Network Growth"" (AGING) Initiative brings together the Health Care Systems Research Network (HCSRN)and the OAICs to advance an interdisciplinary research agenda focused on older adults with multiple chronicconditions (MCCs). The specific aims under the AGING Initiative R33 are: (1) to expand on and further developinnovative methods related to measurement and analytics, observational research, and pragmatic clinical trialdesign and implementation, to inform the development and testing of novel interventions that improve the careand outcomes of older persons with MCCs; (2) to foster the career development and success of new and early-stage investigators, including underrepresented minorities; (3) to create a new core function as part of anelaborated infrastructure that promotes patient-centered research by engaging patients and care partners in allstages of the research process; and (4) to fund a series of ""P-2-R"" (""Pilot-to-R award"") grants. The proposedadministrative supplement builds on the parent project (R33AG057806) by: (1) addressing a research topic ofvital relevance to older adults with multiple chronic conditions (MCCs) - the devastating impact of novelcoronavirus 2019 (COVID-19) in nursing homes; (2) assessing new methods and approaches addressingresearch questions relevant to older adults with MCCs; (3) promoting new collaborations and partnerships toadvance the science of MCCs; and (4) encouraging research that will ultimately translate into the delivery ofhigher quality care for vulnerable populations including residents of nursing homes.",2020,2021,University of Massachusetts Chan Medical School,717173,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,Research to inform ethical issues | Research on Capacity Strengthening,Research to inform ethical issues in Research | Cross-cutting,2020 +C03841,unknown,"Impact of Medical and Recreational Marijuana Laws on Cannabis, Opioids and Psychiatric Medications: National Study of VA Patients, 2000 -2024","Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 is a currently a global pandemic. While mostCOVID-19 cases are mild, severe cases (~15%) require hospitalization, critical cases (~5%) require intensivecare, and many deaths occur. Males and blacks are at greater risk for COVID-19 infection, while poor prognosisis predicted by older age, race/ethnicity, and prior underlying medical conditions. A potentially importantcomplicating risk factor is substance use or substance use disorders (SU/SUD). SU/SUD could increase the riskfor COVID-19 infection and poor prognosis by direct effects of the substances on the cardiovascular, respiratoryor immune systems, or by indirect effects due to the greater prevalence of underlying medical conditions amongsubstance users that predict poor COVID-19 prognosis. Little is known about the relationship between SU/SUDand the risk for COVID-19 infection or poor prognosis, and whether these relationships are modified bydemographic characteristics (sex, age, race/ethnicity, homelessness), medical conditions (e.g., cardiovascular,respiratory conditions, HIV) or state policies (marijuana laws; social distancing policies). To study theserelationships, large databases must include SU/SUD, demographic characteristics, diagnostic, treatment andmortality information.Responding to PA-18-935 and NOT-DA-20-047, we will utilize the Veterans Administration(VA) Electronic Medical Record (EMR) system for this purpose. The VA treats 5.7 million veterans a year. VApatients have high rates of COVID-19vulnerability factors, e.g., male, older age, and chronic medical conditions.A VA Shared Data Resource identifies COVID-19 cases. The large number of VA patients with ICD-10-CM SUDdiagnoses or positive substance use screens will provide extensive data on whether the risk for COVID-19infection and poor prognosis differs by SU/SUD status. Leveraging the research infrastructure established in ourparent grant R01DA048860, we propose a 2-year Competitive Revision to comprehensively address therelationship of SU/SUD to COVID-19 infection and prognosis, and if this varies by demographic, medical andstate characteristics. Aim 1: Determine if SU/SUD (cannabis, tobacco, opioid, stimulants or cocaine) increasethe risk for COVID-19 infection, or in those infected, poor prognosis (e.g., hospitalization, ICU treatment,intubation, death). Aim 2: Determine if associations of SU/SUD with COVID-19 outcomes vary by demographic(sex, age, race/ethnicity, homelessness), clinical (e.g., underlying cardiovascular or respiratory conditions, HIV),or state characteristics. In Year 01, we will focus on 2020 EMR diagnostic, treatment, and vital status death data,using 2019 data to establish that SU/SUD preceded COVID-19. In Year 02, we will incorporate Medicare data toexpand information on those ≥age 65, and incorporate National Death Index data to examine causes of death.Logistic regression will evaluate differences in COVID-19 outcomes by SU/SUD status. Among those withCOVID-19, survival models will determine if time to events indicating poor prognosis differs by SU/SUD. Resultswill fill a major gap in knowledge about the risks for and prognosis of COVID-19 among those with SU/SUD.",2020,2024,Columbia University,158569,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2019 +C03842,unknown,Health Informatics to Model the Scott County HIV Outbreak,"ABSTRACTCOVID-19 cases and deaths are surging in rural areas of the United States. In the last two weeks of April2020, the average number of COVID-19 cases per 100,000 persons rose 125% in rural U.S. counties but only68% in urban counties. During this same time period, COVID-19 related deaths rose 169% in rural areascompared to 113% in urban areas. As of May 4 2020, Georgia had 28,945 confirmed cases of COVID-19 and1,186 COVID-19-related deaths. Georgia is a predominantly rural state. Rural people living with HIV (PLHIV)are at-risk for COVID-19 due, in part, to compromised immune systems and high rates of comorbid healthconditions. Rural PLHIV with comorbid substance use disorders (SUDs) are at particularly high risk for COVID-19 infection. Many rural PLHIV + SUDs lack access to medical and psychological care, must travel vastdistances to receive HIV and SUD treatments, experience high rates of mood disorders, and experiencediscrimination, prejudice, and stigma related to their HIV-status, sexual-identity, and SUD. Georgia is anopportune state in which to study risk for COVID-19 in rural PLHIV + SUDs. In 2017, Georgia had the highestHIV prevalence rate per 100,000 residents of any state. Currently, Georgia ranks 12th in number of COVID-19cases, 5th in hospitalizations due to COVID-19, but has the nation's 7th slowest COVID-19 testing rate. Thisstudy's scientific premise is that, to date, most COVID-19 research has been conducted in urban centers; littleis known about (i) rates of COVID-19 in rural PLHIV + SUDs, (ii) factors predictive of COVID-19 infection in thisgroup, and (iii) types of preventive behaviors in which rural PLHIV + SUDs engage to avoid infection. Thisstudy will assemble a prospective longitudinal cohort of 100 rural PLHIV in northeast Georgia, 50% of whomhave an active SUD (most likely opioid use disorders). The study will be conducted in Georgia's Health District10, in which all ten counties are classified as ""rural,"" 9 are mental health professional shortage areas, and 8are primary care professional shortage areas. To maximize participant safety, all data will be collected usinginnovative remote assessment methodologies. Guided by Wilson and Cleary's model of life quality, participantswill complete assessments at baseline and 3-, 6- and 9-month follow-up that collect: (1) biologic data: CD4count, HIV viral load, viral hepatitis status; (2) behavioral/psychosocial data: tobacco and marijuana use, vapingpractices, depressive symptoms, ways of coping with COVID-19-related stress, and coping self-efficacy; and(3) environmental data: housing status and correctional systems involvement. Surveys will also assessCOVID-19 prevention behavior data (e.g., washing hands with soap and water; social distancing). Analyseswill compare rural PLHIV + SUDs to rural PLHIV without SUDs on rates of engaging in COVID-19 preventivebehaviors. Logistic regression analyses will identify factors predictive of COVID-19 infection in this group.Study findings can inform the development of COVID-19 prevention interventions for rural PLHIV and possiblycontextualize interventions for the unique needs of rural PLHIV + SUDs.",2020,2021,UNIVERSITY OF GEORGIA,142338,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions",2019 +C03844,unknown,COVID-19 Supplement #3 Moderna Trial,"Saint Louis University (SLU) seeks to expand its service to the Vaccine and TreatmentEvaluation Unit (VTEU) network providing resources and expertise to help the network achieveits objectives of evaluating vaccines, preventive biologics, therapeutics and diagnostics forCOVID-19.",2020,2022,SAINT LOUIS UNIVERSITY,11154495,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +C03845,unknown,"Development or improvement of clinical diagnostic tests for SARS-CoV-2 to increase the sensitivity, specificity and ability to provide rapid results","AbstractUnmet Need: q-rtPCR technology has dominated COVID-19 diagnostics and public health screening.Independent of the test developer, q-rtPCR has been shown to have an unusually high false negative rate:15% up to 48% (1). According to the Covid Tracking Project. as of May 16th, 2020, 11 Million COVID-19 testshad been administered in the US (2). With 15% false negative rate, approximately 1.65M people would befalsely classified as free of infection. As might be expected, meta-analysis has shown that the false negativerate for q-rtPCR ""explodes"" before day 7 of infection (3) when viral load is still low, to render q-rtPCRineffective as a tool for detecting weakly symptomatic carriers early, while also lessening its value inepidemiology (4).The Solution: PathogenDx has invented, patented and developed a microarray-based test, DetectX-Rv, andhas submitted it for FDA-EUA review to screen for COVID-19 in NP swabs. The microarray has the capacity totest for multiple viral analytes in parallel with [SARS-CoV-2] as the primary analyte under FDA submission.Content Enhancement. We propose here the addition of a newly identified COVID-19 clade variant, whichhas been hypothesized by others to be more infective (5). DetectX-Rv already contains content needed to testSARS-CoV-2 plus multiple other coronavirus [SARS-CoV, MERS-CoV, CoV 229E,CoV OC43, CoV NL63, CoVHKU1] plus influenza + [PanA & Pan B] which are defined as a set as a ""Pan-Respiratory"" Virus Test.However for the development proposed in this RO1, this ""extra"" coronavirus content will be rationallymodified and used instead as a large set of specificity controls. Other sources of funding outside this RO1will be used to develop the full Pan-Respiratory virus content, as a separate product. Based on the workcompleted thus far, including April 15, 2020 filing to the FDA, we propose that with RO1 funding, the new testvariant (DetectX-Rv-v2) can be made ready (by Q2) for deployment with NP swab collection as an automated96 array/SBS plate COVID-19 test (@576 tests/shift).Sensitivity Improvement. The DetectX-Rv test is based on two Tandem Endpoint PCR reactions in series[Enrichment + Labeling] coupled to microarray hybridization. This technical approach gives rise to detection atsingle nucleotide resolution over a 6-log sample input dynamic range. Most importantly, the [Tandem PCR +Hybridization] assay routinely generates a Lowest Limit of Detection (LLOD) <1 genome per reaction.We anticipate that with this approach, we will routinely detect COVID-19 (signal/noise >20x background) atonly 1 viral genome per reaction. Preliminary data, including that submitted to the FDA EUA program, suggeststhat the LLOD for DetectX-Rv will be roughly 10x lower than for an optimized q-RT-PCR reaction. Thus, with theDetectX-Rv test, COVID-19 should be routinely detected at 100 virus particles/swab.Specificity Enhancement. DetectX-Rv (144 tests) has enormous test capacity relative to q-rtPCR, which hasallowed DetectX-Rv to monitor 3 different sites in the SARS-CoV-2 genome and a human RNA control,concurrently (N1,N2,N3,P) along with a panel of 8 viral controls all performed in parallel and in triplicate, thusallowing confirmation of COVID-19 signals with experimental specificity >10x than attainable with q-rtPCR. Inthe proposed RO1 program, that redundant COVID-19 content will be amended (DetectX-Rv-v2) to include arecently-identified clade variant S-D614G (5) so that initial and variant clades can be measured concurrently.Throughput Enhancement. We are near completion of a program to deploy full automation of DetectX-Rvfunction. As a short term RO1 deliverable, we will develop, by Sept 1, 2020, an integrated suite of technologyfor processing 576 NP swab or saliva tests/shift, in a 96 microarray/SBS plate format, based on the laborburden of 1 technician. The 96 well format employs the same printing technology already in use and the same(patented) microarray fabrication chemistry and is thus low risk. However, by completing the transition to the96 well format, we will have achieved 12,000 arrays/day manufacturing scale, which with support from equityother sources, could be immediately scaled to 48,000 per day.Based the requirements of PAR-20-178, we propose 4 Specific Aims to support this 2 year RO1 program.SA1. Q1. Add Clade & Coronavirus Content Enabling Analysis of SARS-CoV-2 & variants.SA2. Q2. Sensitivity/specificity analysis of DetectX-Rv-v2 vs qRT-PCR predicate: Clinical SpecimensSA3. Q3-5. Simplify DetectX-Rv-v2 Throughput via One pot RT-PCR & Hybridization Rate Enhancement.SA4. Q5-8. Enhance & Validate DetectX-Rv Performance to Diagnose Asymptomatic Transmission",2020,2022,PATHOGENDX,317109,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2020 +C03846,unknown,Identification of the Initial Targets of Transmission,"Summary: The current pandemic of COVID-19 has rapidly spread around the world infecting millions and killingmore than 200,000 people in just months. The first wave of the pandemic is currently peaking in the UnitedStates causing almost 60,000 deaths in the past 6 weeks. This highly contagious virus with the unique features of a high percentage of asymptomatic infected and delayed severe symptoms has wreaked havoc on the population of the US. Without any other options, the US population is flattening the curve by social distancingand self-isolation. To return to normality we need an effective vaccine or therapy to protect populations aroundthe world. Although the SARS-CoV-2 (CoV2) virus is known as a respiratory virus, it clearly has an impactbeyond lung infection with increasing evidence of infection influencing multiple organ systems. Unanticipatedpathologies associated with CoV2 infection such as heart attacks, loss of taste and smell, kidney failure, stroke,and COVID toe suggest possible virus dissemination beyond the respiratory tract. Such dispersed anatomicalinfection is possible because the CoV2 receptor ACE2 is expressed in a variety of tissues, tightly regulated byinnate and adaptive immunity, and plays a key role in vascular homeostasis. High levels of ACE2 expression inthe respiratory tract, liver, kidney, pancreas and cardiovascular tissues correlates with co-morbidities associatedwith death after extended infection. But to better define COVID-19 pathogenesis, it is essential to determine ifthese multiple end organ diseases leading to death are an indirect consequence of CoV2 induced inflammationand hypoxia or a consequence of direct CoV2 infection of various tissues and organs. Through the parent projectand other work, we have developed the concepts of signal guided necropsies and multiscale imaging to identifyand study small foci of SIV replication in the early days after mucosal transmission or rebound after cessation ofantiretroviral drug treatment. The best of these methods utilizes radiolabeled and fluorescently tagged antibody-based probes to identify and in vivo fluorescently label SIVmac239 infected cells. In this emergency competitiverevision application, we will adapt these novel and innovative techniques to study CoV2 infection. Critically,these state-of-the-art methods to identify active sites of CoV2 at the whole live animal method in an unbiasedmanner. Knowing the active anatomical sites of virus replication and inflammation will synergize with modernpathology approaches to provide an increased understanding of the natural history and pathogenesis of CoV2infection. Based on the conceptual and technical innovation described above, combined with the more than 50years of combined virology research expertise of Drs. Veazey and Hope, we believe the application has greatpotential to impact and advance the new field of COVID-19 research. This critical basic understanding willinform the field and advance strategies to stop the pandemic. There is no doubt the completion of the studiesdescribed in this application will advance the field. And we are currently the only ones in the world that can deliverthe described studies at the accelerated pace of research needed for this emergency.",2020,2022,NORTHWESTERN UNIVERSITY AT CHICAGO,786043,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03847,unknown,Impact of Marijuana Legalization: Comparison of Two Longitudinal Twin Cohorts,"This supplemental grant proposes to add questions to extend the aims of the parent project by collectingadditional data related to COVID-19 including financial hardships, social/interpersonal problems, stress, mentalhealth, and substance use changes. Data will also be collected on whether participants are essential workers,were exposed to COVID-19, or have been diagnosed with COVID-19.Parent grant Aim 1: Effect of RML on substance use/misuse, mental health, & psychosocial functionAim 1 extended: Effect of COVID-19 pandemic and RML on substance use/misuse, mental health &psychosocial function.We will test the hypothesis that access to RML increases the likelihood that the stress and disruptionassociated with COVID-19 will lead to increased marijuana use and abuse. Relatedly, we will test the extent towhich increased marijuana use, related to RML and stress/disruptions from COVID-19, is accompanied byincreases in other substance use, mental health disorders, or psychosocial dysfunction.Parent grant Aim 2: Individual differences in the effect of RMLAim 2 extended: Examine individual differences in the effect of COVID-19 pandemic and RML.Examine individual differences in the effects of COVID-19 and legalization by leveraging parallel multi-wavelongitudinal twin studies in CO and MN, which both began collecting substance use, psychopathology, andpsychosocial function during the twins' adolescence. This supplemental assessment will allow us to: a) identifyhow COVID-19 differentially impacts individuals depending on legalization and prior exposure to marijuana; b)examine how individuals differ in their vulnerability and resilience to the effects COVID-19, in the context oflegalization, based on their individual level of risk (e.g., prior diagnosis of anxiety or depression); and c)examine if there are differential associations between COVID-19 and substance use/dependence, mentalhealth, and psychosocial problems depending on legalization status and gender.",2020,2022,UNIVERSITY OF COLORADO DENVER,154303,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C03848,unknown,Cognitive Control in Children of SUD Parents: A Longitudinal Multimodal MRI study,"As the world experiences unprecedented challenges associated with the COVID-19 pandemic, ~15million collegiate students, who are among our nation's healthiest individuals, are facing multiple immediate andlong-term consequences to their mental and physical health, academic careers and post-graduate prospects.These students had been in the middle of an important developmental and educational phase of their lives whenthe COVID-19 pandemic arrived. Their developmental trajectories are now being impacted in unprecedentedways, which has both individual and national importance. However, college students are in the unique positionof being ""embedded"" within the institutional structures of their colleges and universities. With adequate data andknowledge, these institutions can positively impact how students navigate stressors and influence whether theyshow resilience and thrive or develop complicating substance and mental conditions. Using individual academicemails, our partnering academic institutions whose student bodies collectively constitute ~60% of all USundergraduate students, will invite students to join this study. Using an online survey we will obtain consent andcollect baseline information on: demographics, personal/family COVID-19 infections and outcomes, access toCOVID-19 information, effect of the pandemic on housing, food security, finances, social relationships,effectiveness of distance learning, stress related to changes in daily life activities, sources of support, and pre-pandemic/current employment and SU/MH status. We will report these findings in the aggregate and byinstitution to allow for rapid revision of institutional responses. This will lay the groundwork for a definitivelongitudinal study of the long-term effects of the COVID-19 pandemic on these young lives. Study findings arenot only certain to inform academic responses to student needs now, but also identify ways that service providersand academic institutions can better respond to these needs over time.",2020,2021,Columbia University,230375,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C03849,unknown,Viral and immune-mediated CNS pathology during SARS-CoV-2 infection,"Project SummaryThe COVID-19 pandemic has rampantly affected the population of the world and created lasting effects on theeconomy, health and psyche of the global community. Although it shares similarities with SARS-CoV-1, the fullextent of the pathophysiology caused by SARS-CoV-2 is unclear. In particular, extrapulmonary manifestationseffects of SARS-CoV-2 infection remain poorly understood. Case series from China and Europe suggest thatthe central nervous system is involved in the disease process in at least a subset of patients, with some reportsestimating up to 30% of COVID-19 patients having neurological symptoms, including seizure, intractableheadache, and impaired smell and taste. Although there are reports of neurological disease in in COVID-19patients, it is unclear if SARS-CoV-2 invades the central nervous system (CNS). Studies of othercoronaviruses, including SARS-CoV-1, demonstrate clear neurotropism as well as neuroinflammationassociated with other members of this family of viruses. These studies raise the possibility that SARS-CoV-2may cause neurological symptoms either through invasion of the CNS or through an increase in inflammatorycytokines within the CNS. We hypothesize that SARS-CoV-2 infections have neuroinvasive potential and leadto altered and hyperinflammatory immune states within the CNS of infected individuals. We further hypothesizethat infection of the CNS exacerbates respiratory dysfunction through direct toxicity of ACE2 expressingneurons that are critical regulators of cardiopulmonary function. Our investigations will combine the power ofhuman studies with those utilizing mouse models in which we can readily administer virus and assess forpathophysiology. Aim 1, we will determine the CNS immune responses in COVID-19 patients withneurological symptoms. Using a combination of single cell RNA-sequencing, cytokine profiling, viralsequencing and antibody validations, we will fully dissect out the inflammatory responses within the CNScompartment compared to the systemic circulation in COVID-19 patients. Using mouse models, in Aim 2, wewill investigate the encephalitic potential of SARS-CoV-2. Using several complementary approaches toinfect mice with SARS-CoV-2, we will introduce the virus into the central nervous system of mice. Usingdepletion antibodies and various knockout mice, we will identify which immune cells are required forneuropathology in these mice through survival studies, flow cytometry and immunofluorescent staining. Finally,in Aim 3, we will evaluate the effects of CNS infection on respiratory outcomes. Because of the knownexpression of ACE2 in the brainstem, and the brainstem's critical role in regulating cardiopulmonary functions,we suspect that CNS infection with SARS-CoV-2 will exacerbate SARS-CoV-2 respiratory disease.These three aims will help support our hypotheses of how SARS-CoV-2 infections can affect the CNS andrespiratory compartments. We expect that our findings will uncover new strategies to treat patients diagnosedwith COVID-19 and help gain new insight to understanding the biology of SARS-CoV-2 pathophysiology.",2020,2025,YALE UNIVERSITY,417822,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C03850,unknown,Recombinant BCG-based SARS-CoV-2 vaccine,"SummaryThe scale of the humanitarian and economic impact of the COVID-19 pandemic places a high priority on the development of prophylactic and therapeutic countermeasures to better control SARS-CoV-2 infections. Amongthe priorities listed in the NIAID Strategic Plan for COVID-19 research is the need to pursue multiple strategiesto develop a COVID-19 vaccine efficacious across the lifespan, including in the elderly.Recent epidemiologic studies have highlighted the potential for Mycobacterium bovis BCG (the only approvedvaccine for TB prevention) to mitigate through non-specific immunity the prevalence and severity of thesymptoms of COVID-19. Indeed, BCG vaccination has been known since the 1960s to non-specifically improveimmunity against a number of viral pathogens resulting in reduced morbidity and mortality in neonates, childrenand the elderly. Other unique attributes of BCG that make it a vaccine platform of choice for the recombinantexpression of heterologous antigens include the fact that it can produce long-lasting CD4+ and CD8+ T cellresponses, its natural adjuvant properties, its remarkable safety record (> 5 billion doses given to date) and thefact that it is easy and inexpensive to mass-produce.The goal of this project is to leverage ongoing COVID-19 research efforts at Colorado State University togenerate recombinant BCG (rBCG) strains expressing SARS-CoV-2 immunogens (Aim 1) and to assess theimmunogenicity and protective efficacy of rBCG in an established animal challenge model of SARS-CoV-2infection (Aim 2).We hypothesize that the induction of non-specific immunity against SARS-CoV-2 combined with the adaptiveimmune responses elicited by the recombinant expression of validated SARS-CoV-2 antigens will yield rBCG-based COVID-19 vaccines conferring long-lasting protective immunity in people of all ages. Success in thisapproach could rapidly deliver an inexpensive, safe and globally deployable vaccine.",2020,2021,COLORADO STATE UNIVERSITY,411968,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity,2020 +C03851,unknown,SARS-CoV-2 and Autophagy,"PROJECT SUMMARY/ABSTRACTCoronaviruses are major causes of disease worldwide, from the common cold to outbreaks of strains causingsevere and sometimes lethal respiratory distress, including SARS, MERS, and the current outbreak of COVID-19 caused by SARS-CoV-2. It has been observed over the last two decades that multiple coronavirusesinteract with components of the autophagy pathway to rearrange cellular membranes and generate sites forRNA replication. In this application, we propose to test the interactions of SARS-CoV-2 with the autophagypathway. We will rapidly assess whether SARS-CoV-2 has similar interactions with the autophagy pathway asother coronaviruses, then extend the field by identifying how these interactions interfere with viral replication,providing novel therapeutic targets. We will carry this strategy out through three Aims: In the first, we willidentify requirements from the early autophagy pathway for SARS-CoV-2 replication. Data from coronavirusstudies suggest that the autophagy protein LC3 is recruited to generate double membraned vesicles for virusgenomic RNA replication. Other data suggest LC3 is utilized through the ER-associated degradation (ERAD)machinery to generate replication vesicles. We will determine which, if either, of these two pathways is used bySARS-CoV-2. In the second aim, we will determine the role of vesicle acidification in SARS-CoV-2 replication.There is strong evidence that acidification of vesicles plays a role in multiple steps of CoV replication, and wewill identify the role of vesicle acidification in SARS-CoV-2 replication. In the third aim, we will identify thespecific roles of SARS-CoV-2 non-structural proteins in induction of the autophagic machinery. We haveidentified previous studies of expression of non-structural proteins in coronavirus and will use this to guide ourstudy of SARS-CoV-2 proteins. These Aims complement existing studies of autophagy in RNA viral life cyclesby the Jackson Lab while leveraging the existing expertise of the Frieman Lab in studying cell biology ofcoronavirus infections. By completing these Aims, we will understand whether SARS-CoV-2 interacts with theautophagy pathway in a similar or unique fashion compared to other coronaviruses, and extend thecoronavirus field by identifying specific host-virus interactions that may be targeted for COVID-19 therapies.",2020,2022,UNIVERSITY OF MARYLAND BALTIMORE,424875,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03852,unknown,Imaging SARS-CoV-2 proteases for spatio-temporal insight into Covid-19,"Project summary/abstract:This work will build a contrast agent for the SARS-CoV-2 main protease (Mpro; also known as3CLpro) and validate it in an animal model. This contrast agent will have significant value as aresearch tool because it will map and measure Mpro with spatial and temporal resolution.Conventional methods to studying SARS-CoV-2 are based on PCR and serology. These arepowerful and affordable tools for population-wide studies but have limited value in researchstudies because they are in vitro tools that use single time-point sampling. They cannot monitorthe biodistribution and time course of the viral load in vivo or detect the location of viral reservoirs.In contrast, in vivo imaging offers the ability to track biological phenomena longitudinally,quantitatively, and relatively non-invasively. Thus, Aim 1 of this proposal will build a contrast agentfor Mpro based chemiluminescent resonant energy transfer (CRET). Chemiluminescence is a veryuseful in vivo imaging tool because it measures spontaneous emission of photons from contrastagents. Thus, the background emission of normal tissue is zero leading to high sensitivity imagingin contrast to in vivo fluorescence that suffers from high background. When in the CRETconfiguration, the probe is silent; activation via a Mpro-cleavable sequence leads to high signal.We will validate these CRET-based molecules with chemistry and recombinant Mpro. Aim 2 willvalidate this probe with a Sindbis virus models of SARS-CoV-2. We are using this Sindbis modelbecause it is suitable for BSL-2 labs allowing work to proceed immediately unlike wild type SARS-CoV-2 requiring BSL-3. We will express Mpro via Sindbis virus in tissue culture and animal modelsand image viral progression in adult and neonate mice. After validating this contrast agent andimaging approach, the community will have a powerful tool to answer many important questionsrelated to SARS-Cov-2 infection: What is the time course of infection and biodistribution?; Howdoes biodistribution change by route of infection? Are there latent disease reservoirs?; How doprotease levels change in response to therapy? This work is innovative because it will be the firstexample of in vivo Mpro imaging. The significance is motivated by the profound impact Covid-19has had on our society. Importantly, the work is feasible based it will harness Dr. Jokerst'sextensive experience in chemistry and contrast agent development as well as Dr. Siqueira-Neto'sexpertise in infectious disease including Zika virus.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN DIEGO,433927,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03853,unknown,"Oral Microbiome, Nitric oxide Metabolism, and Oral and Cardiometabolic Health","Commensal oral bacteria reduce exogenous (dietary) and endogenous nitrate to nitrite, which is converted to NO, a signaling molecule that regulates vascular tone, inflammation and insulin sensitivity. Our original grant aims to evaluate the role of this ""entero-salivary pathway"" and the related microbial profiles in cardiometabolic health in over 1,000 participants from the San Juan Overweight Adults Longitudinal Study (SOALS) who have pertinent high quality data and biospecimens available at baseline and 3-year follow-up visits (with 79% retention). Endogenous NO also plays important biological functions in the respiratory system such as bronchodilation, vasodilation of the pulmonary blood vessels, and modulation of cytokine production, which could be relevant to COVID-19 outcomes. Furthermore, NO could help prevent COVID-19 infection of the airways because it is involved in ciliary movement and has a demonstrated antiviral activity against SARS-CoV-2, the causative agent of COVID-19. Mouthwash has been recently proposed as a potential strategy for reducing the oral viral load, thus reducing transmission of SARS-CoV-2. However, regular mouthwash use could significantly disrupt the NO production from the entero-salivary nitrate pathway, and it could also possibly interfere with COVID-19 diagnostic tests that use oral or oropharyngeal samples. It is not known to what extent the NO produced exogenously via the entero-salivary pathway contributes to respiratory health and in COVID-19, or how could this be influenced by mouthwash use or other modulators of the oral microbiome. In this revision, we propose to expand the scope of the parent grant to additionally evaluate the role of this pathway, and a key modifiable factor, mouthwash use, in COVID-19 symptoms, diagnosis and outcomes. We propose three new specific aims: 1)To evaluate the association between regular over-the-counter mouthwash use (any mouthwash and few specific brands) and COVID-19 symptoms, diagnosis and outcomes; 2)To evaluate the association of nitric oxide metabolites (nitrate and nitrite) in the saliva with COVID-19 symptoms, diagnosis and outcomes; 3) to evaluate the association of mouthwash use and nitric oxide metabolism with systemic markers of inflammation (IL-6, TNF-a, CRP) and endothelial function (sICAM, VCAM), which may impact COVID-19 progression. As a secondary aim we will also evaluate the association of the salivary nitric oxide metabolites and the oral microbiome with chronic respiratory disease (asthma and chronic obstructive pulmonary disease). Data on COVID-19 and pertinent covariates will be assessed through two sets of interviews conducted over the calls. This supplement expands the scope of the parent grant into a highly relevant and urgent research area pertinent to the transmission, diagnosis and prognosis of COVID-19, and will also evaluate other respiratory outcomes. The additional analyses and insight obtained through this project, will enrich the parent grant, and is expected to have a high",2020,2023,University of Puerto Rico Medical Sciences Campus,224874,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management",2019 +C03855,unknown,SES-Related Disparities in Early Language Development and Child Risk for Developmental Language Disorder,"PROJECT SUMMARY/ABSTRACTThe goal of this study is to understand how the COVID-19 crisis, and related changes incaregiver distress and interactions with infants, affects infant language development over a 12-month period. We propose to gather repeated measures of survey and video-recordedinteraction data from a subsample (n = 100) of SMALL Talk caregiver-infant dyads during one-year of the COVID-19 pandemic. SMALL Talk is actively recruiting and interviewing low-income caregiver-infant dyads in an urban area to study predictors of children's risk of developmentallanguage disorder (DLD) by 54 months. DLD is particularly high among low-SES children(Norbury et al., 2016). However, there are equally important inequalities for DLD risk among low-SES children (Schwab & Lew-Williams, 2016), which may be further exacerbated by theCOVID-19 pandemic. Through this supplemental project, we aim to assess, during one year ofthe COVID-19 pandemic: (1) COVID-19-related forms and frequency of stress and resourceneeds among low-income caregivers with infants; (2) caregiver-infant interactions with primaryand secondary caregivers at multiple, short-term intervals; and (3) how COVID-19-relatedstressors, caregiver distress, and access to resources affect caregiver-infant interactions andinfant language development. We will use remote smart-phone based technology to gather on-line survey data and video recordings of caregiver-infant interactions multiple times during this one-year period. Innovative aspects of this supplemental grant include collecting multiplecaregiver-infant interactions, including secondary caregiver-infant interactions, and using smart-phone technology to conduct in-home assessments among vulnerable groups who are often leftout of digital data collection studies, including COVID-19 studies (Lourenco & Tasimi, 2020). We will use multi-level random-effects models to assess associations among caregiver distress,features of caregiver-infant interactions (including language use and caregiving quality), andinfant language development. We will share this information with key stakeholders to inform thedevelopment of programs and policies to meet immediate needs of low-income families withinfants. We will also publish rapid, open-access research articles and policy briefs to shareevidence of COVID-19-related instability and stress in low-income families and how they areaffect caregiver-infant interactions and child language development in the short- and long-term.",2020,2021,OHIO STATE UNIVERSITY,195000,Human Populations,Unspecified,Infants (1 month to 1 year) | Unspecified,Urban Population/Setting,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2020 +C03856,unknown,NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of Inflammation,"ABSTRACTThis is a request for an Administrative Supplement to expand our current research on the regulation of NLRP3inflammasome activation, carried out under parent award AI043477, with the goal of developing a novel anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome (ARDS). Like its predecessor,the Severe Acute Respiratory Syndrome (SARS)-related coronavirus (SARS-CoV-1), the novel SARS-CoV-2virus, the cause of the COVID-19 pandemic, can establish lower airway infections that cause viral pneumoniathat may progress to ARDS. ARDS is a potentially fatal, severe medical condition that has been estimated tocause 200,000 yearly cases in the U.S., prior to the COVID-19 pandemic and many more now. Several innateimmune cell types including platelets, neutrophils, macrophages and dendritic cells partake in mountinguncontrolled inflammation and tissue injury in ARDS, regardless of its initial trigger. These cells producenumerous inflammatory mediators and cytokines in response to the initial insult, which in the case of COVID-19is viral replication within lung epithelial cells and subsequent cell death. Dying epithelial cells release damageassociated molecular patterns (DAMPs), of which IL-1α and ATP are of primary importance. Together thesemolecules lead to priming (IL-1a) of alveolar macrophages and activation (ATP) of the NLRP3 inflammasome,which mediates production of mature IL-1β and IL-18, which amplify and propagate the inflammatory responsethat culminates in ARDS. Inhibition of this response should reduce much of the mortality and morbidity associatedwith COVID-19. However, since total IL-1 blockade with currently available drugs increases the risk of bacterialinfections, the only suitable strategies for inhibition of SARS-CoV-2 elicited ARDS are either selective IL-1αblockade or inhibition of the NLRP3 inflammasome, which is not involved in anti-microbial defenses. So far,targeting of the downstream cytokine IL-6 had produced mixed results and IL-1a specific antibodies are stillunder clinical development. Moreover, anti-cytokine drugs are quite costly. We recently found the widelyprescribed anti-diabetic drug metformin to be an effective inhibitor of NLRP3 inflammasome activation and IL-1βproduction by activated macrophages in vitro and in vivo. Accordingly, we now ask for additional funding to test and improve the ability of metformin to block the onset of ARDS, first in LPS-challenged Bl6 mice and then inSARS-CoV-2 infected hACE2-transgenic mice. As metformin has a short half-life and macrophages do notexpress the metformin transporters expressed by hepatocytes, we will examine whether metformin-loaded nanoparticles or exosomes given by inhalation allow for more effective inhibition of SARS-CoV-2 elicited ARDS.Importantly, metformin is a very safe and inexpensive drug with strong anti-aging properties that may be offurther value in attenuating the well documented age-related increases in ARDS and COVID-19 risk, attributedto inflamma-aging.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN DIEGO,371655,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C03857,unknown,Effects of COVID-19 on Daily Lives of Older Persons with and without ADRD: National Health and Aging Trends Study Supplement,"AbstractThis application funds a supplement to the National Health and Aging Trend Study (NHATS) to study theeffects of COVID-19 on the daily lives of older adults with and without Alzheimer's Disease and RelatedDementia (ADRD). NHATS interviews a national sample of older adults annually in order to (1) promote scientific inquiry into late-life disability trends and dynamics, their antecedents and correlates, and disparitiestherein and (2) to advance study of the social and economic consequences of late-life disability for individuals,families, and society. The overarching purpose of this supplement is to design, collect and disseminate newdata about older adults' adaptation of their daily lives to the COVID-19 pandemic and consequences for careneeds and wellbeing of those with and without ADRD, drawing on the dual perspectives of older adults andtheir helpers. The specific aims of this supplement are to: 1) Design and administer a COVID-19 mail out/mailback supplement to NHATS 2020 (expected sample sizes=3000-3100 NHATS participants including 600 withprobable or possible dementia; and 2900-3000 family and unpaid helpers including 900 assisting an older adultwith probable or possible dementia); 2) Disseminate a set of rapid release NHATS-COVID-19 public use filesand documentation, a set of final NHATS-COVID-19 files and documentation and a set of transcripts to supportqualitative analysis of the open-ended item about COVID-19's effects; and 3) Conduct targeted analysis of the rapid release COVID-19 items to create a portrait of daily lives and wellbeing of older Americans with andwithout ADRD during the outbreak and the family members and unpaid helpers who assist them. The activitiesproposed for this supplement will facilitate both short- and long-term understanding of the implications of theCOVID-19 pandemic for the care needs and wellbeing of older adults, and how these unfolded differently forthose with and without dementia.",2020,2024,JOHNS HOPKINS UNIVERSITY,630642,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2008 +C03858,unknown,Administrative Supplement to Real-time Wideband Cardiac MRI for Patients with a Cardiac Implantable Electronic Device,"Project Summary/Abstract: While primary manifestations of severe acute respiratory syndrome coronavirus(SARS-CoV-2) infection involve the respiratory system, acute myocardial injury occurs as frequently up to27%, and the 30-day mortality rate is substantially higher in patients with myocardial injury (51.2%) than thosewithout injury (4.5%). Another disturbing trend is the disproportionate impact of COVID-19 on the blackpopulation across the US. In Chicago, blacks (30.1% of population) account for 50.5% of COVID-19 patientsand 69.6% of COVID-19 deaths. These statistics highlight the need to establish the overall prevalence,mechanism, severity, and extent of cardiac injury associated with SARS-CoV-2 and investigate factorscontributing to such glaring health disparities associated with COVID-19. Our primary hypothesis is that acute myocardial injury is more prevalent, extensive, and severe inhospitalized patients with COVID-19 compared to matched hospitalized patients with ORV. Furthermore, wehypothesize that acute myocardial injury associated with SARS-CoV-2 is worse in blacks than whites. To testthese hypotheses, we propose to conduct a case-control study comparing hospitalized patients with COVID-19to hospitalized patients with ORV matched for sex, age, race, viral pneumonia risk score (MuLBSTA), and pre-existing heart disease (coronary artery disease or heart failure). We will enroll equal numbers of whites andblacks to determine factors contributing to racial health disparities in patients with COVID-19. Cardiovascular magnetic resonance (CMR) is the ideal ""one-stop-shop"" imaging test for phenotypingpatients with virus-mediated cardiac injury associated with multiple pathways and manifestations. Thisapproach affords comprehensive assessment of injury, including evaluation of inflammation, necrosis or scar,diffuse fibrosis, contractile function, and hemodynamics. The image quality of a standard CMR, however, maybe unacceptable in hospitalized COVID-19 patients due to two fundamental methodologic deficiencies: (a)lengthy (~60 min) scan time which is too long for sick patients; (b) severe image artifacts caused by dyspnea(55%), arrhythmia (16.7%) and alveolar infiltrates (off-resonance). Leveraging our access to a library of rapid,wideband, arrhythmia-insensitive, free-breathing CMR pulse sequences that were developed for the parentstudy (R01HL151079), we are in a unique position to perform a rapid (20 min) free-breathing CMR tophenotype this cohort who otherwise may not be considered for CMR. The specific objectives of this study are:(a) to determine whether acute myocardial injury differs significantly between COVID-19 and ORV patients; (b)to determine whether cardiac injury differs across race and correlates with social determinants of health; (c) todetermine whether the severity of cardiac injury correlates with the degree of lung injury as assessed withchest X-ray and MuLBSTA. This proposal has high potential impact because new discoveries of cardiac injuryand racial disparities will serve as the requisite evidence for pursuing future therapeutic studies.",2020,2021,NORTHWESTERN UNIVERSITY AT CHICAGO,680708,Human Populations,Black | White,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C03859,unknown,Coronavirus RNA synthesis by multicomponent protein machines,"SUMMARYSARS-CoV-2, the causative agent of COVID-19, has emerged as a global human pathogen sweeping through ourcommunities. The development of strategies to prevent or treat COVID-19 is essential for mitigating disease and limitingfurther viral spread. A key target of antiviral therapeutics is the virus RNA replication complex. The SARS-CoV-2 replication complex is a large multi-subunit machine with multiple co-factors, enzymes and host modulating proteins.How these protein subunits assemble and cooperate to carryout viral RNA replication and transcription remains unclear. The overarching theme of this work is to examine understudied aspects of the coronavirus replication complex with anemphasis on characterizing the effects of existing antiviral therapeutics as well as the discovery of novel targets andcompounds. We are interested in how the virus nsp14 exonuclease contributes to viral RNA proofreading, reducingnucleotide misincorporations and providing natural resistance to nucleoside analogue drugs. We will also explore thefunction of the enigmatic nsp12 nucleotidyltransferase (NiRAN) and will piece together the network of viral proteininteractions responsible for the assembly of the RNA synthesis complex. To this we will use diverse methods includingbiochemistry, biophysics, cell biology, chemical biology and cryo-electron microscopy. These studies will provide newinsight into the workings of this complicated machine, provide new mechanisms of action for existing therapeutics and discover novel antiviral compounds. In addition, the high conservation of components of the replication machineryacross the coronavirus family allows these studies of SARS-CoV-2 to be applicable to future emerging coronaviruses tohead off future viral pandemics before they become global crises.",2020,2025,UNIVERSITY OF WISCONSIN-MADISON,437931,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C03860,unknown,Purinergic modulation of the autoimmune vascular phenotype,"ABSTRACTThis Coronavirus Disease 2019 (COVID-19) supplement will study the role of neutrophil extracellular traps(NETs) as biomarkers and therapeutic targets in COVID-19. The supplement will preserve the parent project'sfocus on ectoenzymes and purinergic signaling as amplifiable counterpoints to neutrophil hyperactivity andexaggerated NET release (NETosis). Indeed, elevated levels of blood neutrophils are an early indicator ofSARS-CoV-2 infection, where they predict severe COVID-19 respiratory disease.Our group and others have recently revealed a critical role for NETs in various thrombo-inflammatory statesincluding sepsis, venous thrombosis, and respiratory failure. NETs are extracellular tangles of chromatin,microbicidal proteins, and oxidant enzymes that are released by neutrophils to corral infections; however, whennot properly regulated, NETs have potential to amplify inflammation and thrombosis. In COVID-19, wehypothesize that NETs will function as powerful biomarkers for predicting progression to respiratory failure.With special relevance to this application, a recent study performed in China suggested potential efficacy of theadenosine-receptor agonist, dipyridamole in severe cases of COVID-19. Dipyridamole is an FDA-approveddrug that our group recently discovered-through work on the parent project-to inhibit NETosis via activationof adenosine A2A receptors (A2AR). The hypothesis here is that A2AR agonists such as dipyridamole willcompensate for virus-mediated deficiencies in the pulmonary ACE2 axis and thereby suppress NETosis.This supplement requests funds to support three complementary Aims. Aim 1 will determine the extent towhich NET levels can be used as predictive biomarkers in COVID-19. Aim 2 will elucidate mechanisms bywhich the ACE2/angiotensin-(1-7) axis regulates COVID-19 neutrophils. Finally, Aim 3 will determine theextent to which adenosine receptor agonism prevents NETosis and macrophage activation in COVID-19.",2020,2021,UNIVERSITY OF MICHIGAN AT ANN ARBOR,390000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2020 +C03861,unknown,The Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC),"PROJECT SUMMARYThe Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2)-driven coronavirus disease 2019(COVID-19) pandemic has fundamentally changed our world, country, community and families. In patients whodie of COVID-19, activation of evolutionarily-conserved inflammatory cascades results in massive increases incirculating levels of inflammatory cytokines producing vascular leak, edema of multiple critical organ (lung,kidneys, heart, brain, liver, GI tract), ultimately leading to multi-organ dysfunction including acute respiratorydistress syndrome (ARDS). There is lack of deep understanding regarding the risk factors for and biology ofCOVID-19. The pandemic has also dramatically highlighted the multiple unmet needs in the care for patientswith SARS-CoV-2 infection including the lack of validated biomarkers, and of effective FDA-approvedpharmacotherapies. Accordingly, this Administrative Supplement seeks to further our understanding throughimmunophenotyping patients who develop COVID-19. We will provide clinical data and samplecollection/processing from a cohort of SARS-CoV2 patients enrolled in Tucson, Arizona. The clinical data andsamples will be transmitted to the central cores that are assigned by the Immunophenotyping Assessment in aCOVID-19 Cohort (IMPACC) study with the overarching objectives to better understand the pathogenesisof COVID-19 disease and to identify immunological pathways that can be used to inform us on how tocombat this disease. In Specific Aim 1, we will recruit and provide clinical data (demographics, clinicallaboratory test results and imaging results, clinical course) longitudinally from patients hospitalized with COVID-19 infection to the designated IMPACC cores in order to establish correlation with immune status and diseaseprogression. In Specific Aim 2, we will provide biological specimens (serum, whole blood, PBMCs,nasopharyngeal samples, endotracheal aspirates) from patients hospitalized with COVID-19 infection to thedesignated cores in order to characterize the immunophenotypes and the immune status and response toinfection. This supplement supports the University of Arizona's participation in IMPACC to facilitate screeningand enrollment of inpatients with COVID-19. The proposed supplement research is within the scope of parentU19 grant entitled ""Dysfunction of Innate Immunity in Asthma"" (1U19AI125357). In summary, the IMPACC studycoordinates a national, multi-institution consortium, collecting detailed clinical data and biologic samples fromhospitalized COVID-19 infected individuals, with the goal of identifying immune signatures/molecular biomarkersassociated with clinical disease course. These data will allow the prioritization of clinical interventions andtherapeutic decision making.",2020,2021,UNIVERSITY OF ARIZONA,561279,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C03862,unknown,Antigen specific T cell responses to two different strains of SARS-CoV-2,"PROJECT SUMMARYCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that is caused by the SARS-CoV-2virus. The disease has caused illness in more than 1.2 million Americans within the last 4 months. However,there are almost no data on human cellular immune response towards this virus. Monitoring the kinetics andbreadth of cellular immune responses associated with clinical resolution of COVID-19 should shed insight on thehuman immune response towards this pathogen during natural infection. We will evaluate SARS-CoV-2 antigenspecific immune responses in subjects with different degree of disease severity that are infected by either theUSA-WAS2/2020 like strain or the FR-HF1465/2020 like strain, the 2 major strains that circulated in Washingtonstate. We will test the hypothesis that coordinated CD4+ and CD8+ antigen specific responses are responsiblefor clearing of the virus. We will also test the hypothesis that subjects that have severe disease and those thatsuccumb to the disease have dysfunctional CD4+T cell responses. We will use transcriptomics analysis toevaluate whole blood, bulk T cells and antigen specific CD4+ and CD8+ T cells. Data will be stratified accordingto the viral strains and disease severity. There will be 3 major aims: 1. Characterize of antigen specific immuneresponses in COVID-19 subjects with severe pneumonia, moderate disease and mild disease, infected by eitherthe USA-WAS2/2020 strain or the FR-HF1465/2020 strain. 2. Characterize epitope specific immune responsein subjects with COVID-19. The hypothesis that the functional defect of antigen specific CD4+ T cells in subjectswith severe disease will be tested. 3. Characterize host RNA-seq signatures of COVID-19 respiratory infectionin whole blood PBMC, bulk and viral antigen-specific CD4+ and CD8+ T cells from COVID-19 subjects infectedby either the USA-WAS2/2020 strain or the FR-HF1465/2020 like strain. A better understanding of antigenspecific immune responses in human should facilitate the identification of effective drug candidates for treatmentand developing new vaccine to prevent infection.",2020,2021,BENAROYA RESEARCH INST AT VIRGINIA MASON,643292,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03863,unknown,Preventing Opioid Overdose Mortality in the United States,"We are proposing an urgent competitive revision for our current grant (R01DA04686702) to study the impactof the novel coronavirus (COVID-19) pandemic on syringe service programs (SSPs) throughout the UnitedStates (US). The COVID-19 pandemic has rapidly proliferated and caused unprecedented disruption to health and health services in the US and has the potential to reverse recent reductions in the nation's opioidoverdose mortality rate. As cities, counties, and states tried to stunt the transmission and impact of COVID-19, they began rolling out various social distancing orders (e.g., Shelter-in-Place). A consequence of these public health mandates and the need to protect people from COVID-19 has been disruptions in services forpeople who inject drugs (PWID). Particularly in the context of the opioid epidemic, understanding how theCOVID-19 pandemic has affected services for people who use drugs is critical to know how to respondwithin the current pandemic and to be better prepared for future public health crises. SSPs have been themainstay for community-based prevention efforts for PWID and have pioneered efforts for implementingoverdose education and naloxone distribution (OEND) and improving enrollment into medications for opioiduse disorder (MOUD) programs. SSPs are considered an ""essential service"" and have not been mandated tosuspend services during Shelter-in-Place orders. As part of our nationwide study of SSPs, our study teamhas documented that SSPs are facing unprecedented challenges and adapting implementations, asnecessary. Leveraging our ongoing study, we propose to build a comprehensive understanding ofadaptations made in response to COVID-19. Using the exploration, preparation, implementation, andsustainment (EPIS) framework, we propose to systematically assess the impacts of the COVID-19 pandemicon SSP services in the US. Our proposed aims are as follows: Aim 1: To characterize the response toCOVID-19 regarding the delivery of syringe services, overdose education and naloxone distribution, andmedications for opioid use disorder among SSPs; Aim 2: To describe barriers and facilitators among SSPsregarding implementation of syringe services, overdose education and naloxone distribution, andmedications for opioid use disorder during the COVID-19 pandemic. To achieve these aims, we will conducta cross-sectional study with all SSPs (N = 407) in the US in late summer/fall 2020. In addition, we willconduct in-depth interviews with 36 SSPs from geographically diverse urban, suburban, and rural locationswhere we observe varying levels of implementation experiences-de-implementation of services, adaptedimplementations, and implementation as usual-during the COVID-19 pandemic. Understanding how theCOVID-19 pandemic has impacted services for PWID is critical for improving our response within the currentpandemic and being better prepared for future pandemics.",2020,2021,RESEARCH TRIANGLE INSTITUTE,164420,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Drug users,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2018 +C03864,unknown,"Developing and Applying a Safe, Tractable Derivative of SARS-CoV-2","PROJECT SUMMARYInfectious stocks of SARS-CoV-2 are now generally studied under BSL3 containment limiting the numberof researchers who can work with it and increasing the difficulties of performing some of their experi-ments. We shall develop a derivative of SARS-CoV-2 that is replication-competent, but propagation-defective, supporting only a single round of infection, and therefore safe to examine under BSL2 contain-ment. Many more scientists will then be able to study this pathogen. This derivative, termed CoV-2.def,will be carried in cells such that its expression is repressed and can only be transcribed upon treatmentwith an inducer, doxycycline. It will also have two deletions of the structural proteins encoded by genes,E and M, so it will not be infectious in their absence. Neither of these engineered viral genes will have homology to CoV-2.def thus minimizing the chance of their recombining with CoV-2.def. M will be supplied in trans and can be expressed only upon induction. E will be supplied only by transfection ofeither an mRNA or the protein itself. These latter properties are designed to ensure that the cells thatcarry CoV-2.def do not accumulate viral RNAs during their passage that could contribute to recombina-tion and that the derivative can infect cells for only a single round.The derivative CoV-2.def will be constructed in multiple phases in order to ensure its safety and function-ing at each step. The first two orfs, 1A and 1B, which encode non-structural proteins of SARS-CoV-2, willbe introduced into a plasmid vector derived from an Epstein-Barr Viral plasmid replicon. These orfscomprise the first 2/3 of the viral genome and will be regulated by the binding of a Tet-KRAB repressorso that they can be expressed only following induction by treatment with doxycycline. This constructionwill be examined for its conditional expression and for its dependence on M and E and perhaps on the Ngene too for its release in extracellular particles. Only when these properties are established as beingeffective and safe will the intact CoV-2.def be constructed and tested under BSL3 containment. AfterCoV-2.def is found to be replication-competent, propagation-defective, and support only a single round ofinfection, it can be examined safely in BSL2 labs.Two sets of experiments with CoV-2.def will be conducted to improve treatment of patients with COVID-19. Because CoV-2.def supports one round of infection, it can and will be used to measure titers of neutralizing antibodies in the plasma of patients. Neutralizing antibodies can only be measured withinfectivity assays so that CoV-2.def is a powerful, safe tool with which to evaluate this facet of the adap-tive immune response and correlate it with patient outcomes. We shall measure these titers in samplesprovided by the Translational Science BioCore (TSB) BioBank, which is a shared service at the Univer-sity of Wisconsin Carbone Cancer Center, and be able to assess how being a cancer patient may affectthis immune response to COVID-19. It is also clear that an effective, safe assay for the titers of neutraliz-ing antibodies can be used to identify samples of plasma that can be provided therapeutically to patientswith COVID-19.In the second set of experiments, engineered derivatives of CoV-2.def will be used in two complementaryCRISPR/Cas9 screens to identify cell-dependencies of SARS-CoV-2. We shall identify these cellulardependencies by establishing a library of gene knockouts with CRISPR/Cas9, infecting this library withtwo engineered derivatives of CoV-2.def to select for and against the cells that support infection, and determining the responsible genes by sequencing the sgRNAs in the selected populations. Inactivatingthese genes in our confirmatory experiments should block infection by CoV-2.def and thereby highlightcellular genes and pathways which are targets for anti-viral therapies.",2020,2021,UNIVERSITY OF WISCONSIN-MADISON,75850,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C03865,unknown,Innate Immune Regulation of the Epithelium in Chronic Rhinosinusitis with Nasal Polyps,"ABSTRACTThe ongoing outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major threat to global health.The nasal passages are the key portal of entry for airway virus infections, and evidencesuggests that the nasal epithelium is a key reservoir for SARS-CoV-2 and a source of viralshedding that accounts for high transmissibility and elevated rates of COVID-19. We hypothesize that diminished interferon-induced innate immune responses in infected nasal epithelial cells is a primary mechanism allowing rapid viral replication without cytotoxicity. Theparent grant focuses on how human sinonasal epithelial cell populations participate in immunedefense and damage repair. In this supplement proposal, in response to NOT-AI-20-031, wewill extend these studies to research in depth the epithelial cell innate immune response toSARS-CoV-2. Specifically, delayed interferon signaling may prevent induction of nitric oxide,which has been previously shown to inhibit viral entry and replication. Nitric oxide can beinduced in nasal epithelial by stimuli other than interferon, including through activation of bittertaste receptors expressed on the cilia. There are a number of approved medications in clinicaluse that taste bitter and can bind to bitter taste receptors. Among these, certain anti-nausea and antihistamines are particularly strong bitter taste agonists. In this proposal, we will test the ability of these medications to inhibit SARS-CoV-2 infection of primary nasal epithelial cells invitro. We will then use pharmacologic modulators of the bitter taste signaling and nitric oxidepathways to establish the mechanism of action of drugs that decrease infection. We will also determine if these medications impact the interferon response to SARS-CoV-2 infection. Ifsuccessful, these studies may lay the foundation for novel therapeutic approaches to enhancethe initial epithelial cell innate immune defense against SARS-CoV-2 infection, limitingprogression of COVID-19 and decreasing transmissibility.",2020,2021,JOHNS HOPKINS UNIVERSITY,141446,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies | Prophylactic use of treatments,2020 +C03866,unknown,ST6Gal-1 Sialyltransferase in Inflammation,"Project Summary (Supplement)COVID-19 is a pandemic in which the high mortality rate is driven by high infectivity and rampant transmissionof the causative corona virus, SARS-CoV-2. The unpredictable and very rapid life-threatening deterioration in some but not all viral-positive patients remains unsolved and requires immediate attention. Plasmapheresis,used to treat patients with acute organ transplant rejection, ameliorates the severe symptoms of COVID-19patients, suggesting a similar immune-related dysfunction in COVID-19. Emerging studies implicate altered glycans and glycosylation as central but overlooked contributors in COVID-19 pathogenesis. Among these studies: 1) Blood group A patients have significantly worse outcomes than blood group O; 2) the SARS-CoV-2 displays unique glycan structures, the TF and Tn antigens that are normally only expressed in cancer; 3)engaging host sialic acid glyan epitopes to facilitate viral entry and dispersal is well document in related coronaviruses although not yet reported for SARS-CoV-2. Our preliminary data supports a glycosylation-axis in COVID-19 pathogenesis. Comparing 10 viral-positive patients with 10 healthy volunteers, we showed patient plasma have 1) IgGs and IgMs directed again a numberof prominent cell surface glycan structures, including against TF and Tn antigens; and 2) a striking shift of anti-ABO from predominantly IgG to IgM (p<0.001 with just 10 patients and 10 volunteers). Additional observations,part of the ongoing parent NIAID-funded R01, identified a blood-borne glycan-modifying enzyme, ST6GAL1 withpleiotropic functions in promoting Ig production, B cell maturation, facilitating transitional B cell survival duringselection, while attenuating inflammation by muting cytokine release from airway macrophages. We have alsoreported that platelets as critical contributors to ST6GAL1 function, natural circulating ST6GAL1 levels fluctuatedepending on disease status, and that inoculation of recombinant ST6GAL1 mitigated acute airway inflammation in mice. We propose using an increase number of patient and healthy donor plasma to expand upon the unique anti-glycan antibodies and correlate with disease status. We will also address how glycosylation abnormalities drive plate dysfunction in COVID19 by assessing the ability of patient anti-glycan antibodies to activate platelets.These Aims should yield definitive insights into blood glycans in COVID-19. Future directions will test the utility of glycans, glycan-mimetics, and/or recombinant glycan-modifying enzymes such as ST6GAL1 as therapeutic modalities for COVID-19.",2020,2022,ROSWELL PARK CANCER INSTITUTE CORP,183648,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C03867,unknown,Regional Healthcare Ecosystem Analyst (RHEA) Modeling the Environment (MODE): SARS-CoV-2,"PROJECT SUMMARY ABSTRACTWith the ongoing COVID-19 coronavirus pandemic, the potential environmental transmission of severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of significant concern, especially inhospitals. Choosing and coordinating the right approaches (e.g., environmental cleaning and monitoring,airflow regulation) in the complex hospital environment can be challenging, given frequent patient and staffturnover, limited resources, and the potential rapid spread of SARS-CoV-2. Further, developing newapproaches requires guidance for design and implementation. Computational modeling with economic,operational, and epidemiologic components can assess the value of approaches with various features andefficacies to guide design and implementation in complex systems. Our Regional Healthcare EcosystemAnalyst (RHEA) Modeling the Environment (RHEA-MODE) project already will be developing agent-basedmodels (ABMs) to help better understand and prevent the environmental transmission of methicillin-resistantStaphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), two pathogens that commonlycause healthcare-associated infections (HAIs). This offers a key opportunity to ask and answer similarquestions about SARS-CoV-2. Therefore, the goal of this proposed RHEA-MODE: SARS-CoV-2supplemental project is to develop ABMs of hospitals to help better understand the role of the hospitalenvironment and environmental cleaning and monitoring methods in preventing and controlling thespread of SARS-CoV-2. While there may be some similarities with MRSA and VRE, the characteristics (e.g.,contact, air transmission) and consequences (e.g., various COVID-19 outcomes) of SARS-CoV-2 are different,requiring different representations in the ABMs. The virus also requires different interventions (e.g., N95 maskuse) and potentially different environmental cleaning (e.g., more aggressive standard disinfectant use, newprocedures like ultraviolet light irradiation, air filtering) and monitoring (e.g., checking compliance with cleaningprotocols and for the presence of virus in the air and on surfaces). Our team is led by Bruce Y. Lee, MD MBA,who has been part of the Models of Infectious Disease Agent Study (MIDAS) network for over 12 years andhas over two decades of experience in industry and academia leading large mathematical and computationalmodeling projects to better understand, prevent, and control infectious diseases, including being embedded inthe U.S. Department of Health Human Services during the H1N1 flu pandemic to assist the national response.Specific Aim 1 for this project will develop detailed computational representations of sample hospitals andtheir environments and determine the role of the hospital environment in the transmission of SARS-CoV-2under various conditions and circumstances. Specific Aim 2 will explore how various environmental cleaningand monitoring products, methods, approaches, and strategies can reduce SARS-CoV-2 transmission, spread,and associated health and economic outcomes based upon the simulation models from Aim 1.",2020,2024,City University of New York,322626,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +C03868,unknown,CTU COVID Testing Supplement,"Emory-CDC Clinical Trials Unit-Supplement for COVID-19 testingProject Summary/AbstractThe emerging COVID-19 pandemic, caused by the SARS-Co-V-2 coronavirus has already caused over 1.3million infections and over 80,000 deaths in the US as of May 13, 2020 (1). In the absence of effectivetherapies or a vaccine, non-pharmacologic measures such as social distancing, face masks and lockdownshave been implemented for prevention of COVID-19 infection which has helped to decrease the spread.Additional critical measures to control the pandemic include identification and isolation of infected individualsand contact tracing which requires scaling up of testing for all people. As of May 13, 2020, the US has beenable to perform ~ 9 million tests, or around 29,000 tests/million population. While this is a large number and, infact, more tests performed than any other country in the world, it is still not sufficient. Several investigatorssuggest that 3 - 4 million tests/week are needed in order to test ~ 1% of the US population.Atlanta, Georgia has not been spared by the COVID-19 pandemic. While these is no data available for City ofAtlanta, the 5 counties that form the Atlanta metropolitan area (Fulton, DeKalb, Gwinnett, Clayton and Cobb)have reported 11,771 cases which represents 34% of the total cases reported in the State of Georgia (2). Thecharacteristics and clinical outcomes of hospitalized patients with COVID-19 in Georgia have been recentlydescribed (3). Among 305 patients, the median age was 60 years with 29% of the patients under the age of 50.Also, 83% were African American and although co-morbid conditions such as diabetes, obesity andhypertension were common, 1 in 4 patients admitted did not have any high-risk conditions. In a study amongCOVID-19 patients in three hospitals where Emory University faculty provide medical care, 20 of 530 personshad HIV co-infection. Median age was 57 years, most had controlled HIV and comorbid condition such ashypertension and diabetes.The Emory-CDC HIV Clinical Trials Unit has two Clinical Research Sites in Atlanta, the Hope Clinic of theEmory Vaccine Center and the Ponce de Leon Clinic. Both sites offer great opportunities to expand testing,not only to their existing patient populations but also to the neighboring communities. In this application wepropose to use the existing infrastructure for research and will add expanded facilities for COVID-19 testing.Since testing for COVID-19 must incorporate safety measures for the staff, we plan to develop expandedfacilities including temporary tents to accommodate potential drive through scenarios, and/or a mobile healthclinic.",2020,2020,EMORY UNIVERSITY,599941,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03869,unknown,Multi-Contrast Chest Radiography (MC-CXR) for COVID-19 Diagnosis and Screening,"AbstractAs of 4/30/2020, the Coronavirus Disease 2019 (COVID-19) has infected more than one million people andcaused 60,057 deaths in the United States. Neither the clinical symptoms nor the radiological features of COVID-19 are specific to the disease, resulting in significant challenges to the screening and early diagnosis of thishighly infectious disease. The current gold standard method for COVID-19 diagnosis, the reverse transcriptasepolymerase chain reaction (RT-PCR) test, has a relatively long turnaround time. Chest x-ray radiography (CXR)has been widely used in the United States for COVID-19 assessment since the first case reported in the US.However, the major challenge with the use of CXR is its low sensitivity and specificity to COVID-19, which islargely attributed to the lack of x-ray absorption contrast sensitivity to mild alveolar damages in the early phasesof COVID-19. In this Emergency Competitive Revision, we offer a quick response to the imperative clinical needto improve the diagnostic accuracy of CXR to COVID-19 by leveraging the multi-contrast x-ray imagingtechnology developed in our ongoing R01 project (EB020521). In particular, the x-ray dark field contrastmechanism is orders of magnitude more sensitive to partial fillings or collapses of alveoli and thus is expectedto offer a significant boost to CXR's sensitivity to alveolar damage. We will quickly construct a multi-contrastchest x-ray radiography (MC-CXR) system, characterize its physical performance, evaluate its radiation safety,and optimize its scan protocols. Finally, we will conduct a pilot human subject study to collect initial evidence forits clinical value in diagnosing COVID-19. Considering the high likelihood for a second wave of COVID-19, theavailability of the proposed MC-CXR system can facilitate the hospital systems to cope with additional rounds ofpatient surge by providing rapid ""entrance"" assessment of COVID-19.",2020,2021,UNIVERSITY OF WISCONSIN-MADISON,404441,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03870,unknown,"BDD CIS: Big Data Driven Clinical Informatics & Surveillance - A Multimodal Database Focused Clinical, Community, & Multi-Omics Surveillance Plan for COVID19","AbstractWith South Carolina's population already being vulnerable to poor health as evidenced by poor national healthrankings, challenging rural geography and health professional shortages, the impact of the novel CoronavirusDisease 2019 (COVID-19) will be long lasting in the state. Patient morbidity and mortality rates alreadycontinue to increase, with ongoing economic damage to health systems and businesses. The speed oftransmission and geographical spread of COVID-19 across South Carolina and the United States is alarming,which combined with the novel nature of the disease justifies the need for accelerated research to combat thispandemic. As clinicians and frontline health workers battle to save lives, creating a data environment thataccelerates research is key, and necessary to battle the disease. Access to such information will equip frontlinehealth workers to continue the fight against the disease. This proposal will build the capacity for acceleratedresearch and intelligence gathering by coalescing multiple state partners and leveraging relevant data fordiscoveries around COVID-19. To accomplish this, this proposal aims to (1) create a de-identified linkeddatabase system via REDCap and a mobile application (app) to collate surveillance, clinical, multi-omics andgeospatial data on both COVID-19 patients and health workers treating COVID-19 patients in South Carolina;(2) examine the natural history of COVID-19 including transmission dynamics, disease progression, andgeospatial visualization; and (3) identify important predictors of short- and long-term clinical outcomes ofCOVID-19 patients in South Carolina using machine learning algorithms. These aims will be accomplishedthrough collaborations with multiple state agencies and stakeholders relevant to COVID-19 and the creation ofa REDCap database and mobile app that allow for coalescing relevant data in a timely fashion, combined withleveraging of statewide integrated data warehouse capabilities.",2020,2022,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,626275,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease surveillance & mapping | Prognostic factors for disease severity,2017 +C03871,unknown,A Reaction- Diffusion-Based Approach for Nucleic Acid Quantification,"ABSTRACTThe recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a largeglobal outbreak and become a major global public health concern. It is still spreading rapidly to many countriesdespite extensive implementation of control measures. So far, SARS-CoV-2 has affected more than 2,544,792patients and resulted in more than 175,694 deaths all over the world. Rapid and accurate detection of novelcoronavirus SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), plays a crucialrole in facilitating early intervention and reducing rapid transmission of the virus. Reverse transcriptionpolymerase chain reaction (RT-PCR)-based molecular detection is highly sensitive and specific method andhas been widely used for early diagnostics of the COVID-19 disease. However, it relies on expensiveinstruments, and well-trained personnel, which are not suitable for point of care settings such as drive-thrutesting sites, home care, small clinics with limited infrastructure and resources. Here, we propose to developand validate a rapid, low cost, CRISPR-based molecular detection technology for early diagnostics of theCOVID-19 disease at the point of care. To achieve the goal, we have assembled a highly interdisciplinaryresearch team (e.g., bioengineer, clinician, virologist and industry partner). We will use this supplementalproject to generate preliminary data to: i) develop and optimize our point of care diagnostic technology forSARS-CoV-2 detection, and ii) evaluate and validate the clinical feasibility of our technology for earlydiagnostics of the COVID-19 disease by using COVID-19 patient samples. The pilot-test data obtained in thisproject will provide a basis for future large-scale research and commercial applications. If successful, suchsimple and rapid diagnostic technology will open a new pathway for cost-effective, molecular detection of theCOVID-19 disease at the point of care.",2020,2021,UNIVERSITY OF CONNECTICUT SCH OF MED/DNT,331006,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03872,unknown,"Identifying pre-sepsis opportunities for early, targeted intervention","ABSTRACT/PROJECT SUMMARYSARS-CoV-2, the novel coronavirus resulting in COVID19 disease, has caused a global pandemic ofunprecedented impact. In just over three months, SARS-CoV-2 spread has infected more than 2 millionindividuals and resulted in at least 150,000 deaths. Non-pharmacologic interventions (NPIs), like socialdistancing and shelter-in-place measures, have proven to be the only effective strategy available today tomitigate rapidly growing outbreaks. However, the effectiveness of social distancing depends on earlyidentification of viral spread, since even short delays in NPIs can result in overwhelming surges in acute illnessand healthcare demand. Unfortunately, current prediction models of SARS-CoV-2 viral spread are based onlagging or incomplete indicators of infections like COVID19 case positivity, hospitalization, or death rates. As aresult, these prediction models may have limited efficacy during the earliest stages of viral spread, when NPIscan have the greatest impact. This project will use methods my laboratory has developed to predict sepsis - alife-threatening infectious disease marked by a dysregulated host response - that incorporate novel real-timedata to identify and compare the value of early indicators of SARS-CoV-2 viral spread. We will compare thepredictive utility of these data in SARS-CoV-2 with influenza, a seasonal viral disease that can cause sepsiswhile also resulting in surges in healthcare demand. We will use a unique source of highly-detailed electronichealth record data arising from an integrated health system with more than 200 medical offices and 21hospitals caring for 4.4 million patients. Our findings will have broad and immediate impact for predictingSARS-CoV-2 viral spread that can inform effective strategies for COVID19 mitigation by patients, clinicians,public health agencies, researchers, and health systems.",2020,2023,KAISER FOUNDATION RESEARCH INSTITUTE,401918,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2018 +C03873,unknown,Deciphering mechanisms of COVID-19 induced anosmia,"Project Summary/Abstract In this Competitive Revision proposal, we seek to investigate the non-cell autonomous effects of Covid-19 infections in olfaction. Our preliminary data suggest that induction of pro-inflammatory/antiviral pathwaysresult in disruption of inter-chromosomal genomic interactions, and downregulation of Olfactory Receptor (OR)gene expression. Since antiviral responses are expected be elicited upon Covid-19 infection, we hypothesizethat disruptions in nuclear architecture and OR expression account for the reported olfactory deficits in infectedpatients. Thus, we propose to analyze human autopsies of the olfactory epithelium, to decipher whether Covid-19 infections disrupt genomic interactions required for OR transcription. We will complement our studies inhuman autopsies with experiments using mice infected with SARS-CoV-2. RNA-seq, in situ HiC andimmunohistochemistry experiments in human and mice will reveal the molecular mechanisms by which Covid-19 induces olfactory dysfunction. Our experiments will provide critical insight to the mechanisms by which thevirus hijacks molecular and physiological processes of the host cell, opening new potential avenues for theprevention, diagnosis and treatment of Covid-19 infection.",2020,2021,COLUMBIA UNIVERSITY HEALTH SCIENCES,202500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C03874,unknown,Assess and Adapt to the Impact of COVID-19 on CVD Self Management and Prevention Care in Adults Living with HIV (AAIM-High),"Social distancing in the context of the SARS-CoV-2 coronavirus and COVID-19 disease pandemic may amplifyisolation and loneliness due to the requirement to limit in-person interactions with loved ones, friends,community members, healthcare providers, etc. Social isolation increases susceptibility to illness, stress,hypertension, depression, and mortality and decreases engagement in self-management and physicalactivity. People living with HIV (PLWH) are at increased risk for cardiovascular disease (CVD) and areparticularly vulnerable to the stress and social isolation caused by the public health measures to combatCOVID-19. Using mixed-methods and a human-centered design approach, we have developed and arecurrently testing in a randomized controlled trial a nurse-led intervention to EXtend the HIV/AIDSTReatment cAscade for CVD prevention (EXTRA-CVD). Racially and ethnically diverse participants onsuppressive antiretroviral therapy (n=300 total; 64 enrolled to date) with high BP AND high cholesterol from 3HIV-specialty clinics [University Hospitals, MetroHealth (both Cleveland, OH) and Duke Health (Durham, NC)]are randomized 1:1 to intervention vs. education control. In response to NOT-OD-20-757, we propose thisadministrative supplement to leverage the EXTRA-CVD platform to Assess and Adapt to the Impact ofCOVID-19 on CVD Self-Management and Prevention Care in Adults Living with HIV (AAIM-High). Theproposed activities are IRB approved and ready to begin immediately if funded. In a formative Aim 1, wewill assess the impact of COVID-19 related social distancing on HIV and CVD self-managementbehaviors among participants in EXTRA-CVD using well-validated instruments, NIH common data elementsand a sequential mixed-methods design. In Aim 2, we will conduct a hybrid type 3 implementation study toevaluate the implementation of a virtually enhanced EXTRA-CVD intervention to improve BP control inPLWH. Using a human-centered design approach, we will convene our EXTRA-CVD stakeholder DesignTeam, to refine virtual enhancements to the intervention, such as virtual adherence support groups,cardiovascular prevention specialist remote consultation, and community health worker technologycoaches. We will enroll adult PLWH participants (n=75) on suppressive ART with high BP whom are otherwiseineligible for the parent trial because they do not also have high cholesterol or because they are unwilling orunable to participate in the in-person trial. Thus, this supplemental study arm will not poach potentiallyeligible participants from the parent trial. Implementation outcomes based on a RE-AIM framework will becompared to parent trial participants: reach (% agreeing to participate), effectiveness (change in homesystolic BP), adoption (frequency of home BP use), implementation (qualitative assessment offeasibility/acceptability), and maintenance (qualitative). This supplement will increase the impact andscalability of the EXTRA-CVD study without compromising the integrity or feasibility of the parent trial.",2020,2021,CASE WESTERN RESERVE UNIVERSITY,446517,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2018 +C03876,unknown,Mechanisms of immune dysregulation in human PI3Kgamma deficiency,"Project Summary Many severe immune diseases in young patients with infection susceptibility and/or immune-mediatedtissue damage are caused by a single-gene defect resulting in an inborn error of immunity. We have a long-standing interest in intensive investigation of severe immune diseases of childhood. Our approach is to pursuerigorous genetic and immunologic studies that define the genes, cell types, and pathways underlying pathologyto glean clinically relevant insights into fundamental human biology directly from patients. Currently, the genetic,molecular, and cellular drivers of susceptibility and pathogenesis in rare cases of severe SARS-CoV2-relateddisease in young, otherwise healthy individuals are unknown. Defining these drivers will not only address theurgent health needs of children and teenagers afflicted with the recently surging 'multisystem inflammatorysyndrome in children' (MIS-C) and severe respiratory manifestations associated with SARS-CoV2 infection butwill also provide fundamental knowledge about immunopathology mechanisms that are a general feature ofCOVID-19 across the age spectrum. We have built an growing cohort of young COVID-19 patients and bankedDNA, cells, and serum from saliva and peripheral blood samples to enable us to tackle this urgent crisis. Ourpreliminary data demonstrate feasibility to obtain suitable samples for multi-dimensional analysis of leukocytesfrom these patients and also raise testable hypotheses about the initiating and triggering events in MIS-C. Usingprimary human cells and cutting-edge technologies, two specific aims will be pursued. Aim 1) To define geneticsusceptibility to severe COVID-19 in young, otherwise healthy subjects. Aim 2) To elucidate immunemechanisms mediating severe inflammatory responses in these children and teenagers. The results of theseinvestigations will provide significant insights into COVID-19 genetics and inflammation and will lay thegroundwork to help advance our understanding and treatment strategies for this world-wide pandemic.",2020,2021,YALE UNIVERSITY,251251,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C03877,unknown,Administrative Supplement to CGRP's effect on hearing and balance in a mouse model of migraine,"The purpose of this COVID-19 research supplement is to critically evaluate if a calcitonin gene-relatedpeptide (CGRP) receptor antagonist can mitigate both neuroinflammatory and hyper-immune responses toSARS-CoV-2 infection. In December 2019, the coronavirus disease (COVID-19) caused by severe acuterespiratory syndrome CoV-2 (SARS-CoV-2) was identified. There are now over ~5.5 million confirmed casesworldwide (1.6 million US), and 345,000 deaths (~100,000 US). COVID-19 causes a respiratory illness like theflu with symptoms such as fever, cough, loss of smell, fatigue, sputum production, shortness of breath, sorethroat, headache, chills, and nausea or vomiting. Approximately 80% of people have mild disease andrecover. However, in those remaining 20%, COVID-19 is severe and there is evidence that progression to themost serious type of COVID-19 illness is related to a hyper-immune response (ie, cytokine storm). Currently,there are no effective vaccines or treatments available for COVID-19. In this supplement we will test the abilityof CGRP-receptor antagonists to inhibit the neuroimmune consequences of SARS-CoV-2 infection, usingtemperature and nausea as an indicator of SARS-CoV2 infection, as we are doing in our parent grant toassess migraine nausea pain. A humanized mouse model has been developed for studying SARS-CoV2,where mice express the human angiotensin-converting enzyme 2 (hACE2), enabling us to model Covid-19 inthe mouse. The FDA has recently approved Biohaven Pharmaceuticals to proceed to a phase 2 clinical trial ofits CGRP-receptor antagonist (vazegepant; currently in phase 3 trials for migraine) to treat patients with severeCOVID-19, suggesting that the neuroinflammatory reaction that is initiated by CGRP in response to SARS-CoV2 could be a therapeutic target for treating severe Covid-19, and that the non-invasive readouts ofneuroinflammation that we are developing could be used to rapidly identify at risk patients. Our hypothesis isthat mild to severe COVID-19 symptoms will occur in the transgenic hACE2 mouse that has been infected withSARS-CoV-2, and that a CGRP receptor antagonist will mitigate these symptoms. The specific aims are totest the following hypotheses that transgenic mice and non-carrier littermates infected with SARS-CoV-2 willexhibit: aim 1) mild severe symptoms based on viral load, and if these symptoms are less severe when treatedwith a CGRP-receptor antagonist; and aim 2) reduced fever and nausea-like pain when treated with a CGRP-receptor antagonist. Information gained from these studies will provide a direct assessment of whether aCGRP-receptor antagonist can mitigate both mild and severe symptoms associated with SARS-CoV-2infection. This proposal also impacts the development of robust preclinical in vivo assays of COVID-19symptoms, paving the way to develop and test future therapeutics for COVID-19.",2020,2023,UNIVERSITY OF ROCHESTER,192500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2018 +C03878,unknown,Defining The Immune Response to SARS-CoV-2 in Aging,"PROJECT SUMMARY / ABSTRACTThe rapid progression of the SARS-CoV-2 pandemic and associated COVID-19 disease in the first 3 months of2020 highlight the urgent need for research to understand the pathogenesis of the disease at the cellular leveland how the immune system responds to this infection. Although persons of any age and gender can be infectedand develop symptomatic disease, patients 60 years or older with or without co-morbidities are particularly proneto severe consequences of the infection ultimately leading to death. While data from all over the world arebeginning to give a better picture about the epidemiology and clinical progression of COVID-19, limitedinformation about the pathogenesis of the disease at the cellular level is available. A recent report showed thatthe SARS-CoV-2 viral spike protein (S) uses the SARS-CoV receptor ACE2 for binding and that the mammalianserine protease TMPRSS2 primes the S protein to allow viral fusion with the cell membrane and viral entry.However, little is known about how viral binding and entry affects specific immune cells, and what pathways areinvolved in the immune response to SARS-CoV-2 and whether differences in this immune response could explainthe increased propensity of individuals aged >60 to develop severe consequences of infection. We will begin toaddress this knowledge gap via a multi-omics approach using: 1) primary human PBMCs isolated from normalyoung and aged individuals and subsequently treated in vitro with the SARS-CoV-2 S protein or infected withSARS-CoV-2 and 2) samples from patients infected with SARS-CoV-2.",2020,2022,MASSACHUSETTS GENERAL HOSPITAL,361494,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03879,unknown,Pilot study of RTB101 as COVID-19 prophylaxis in older adults,"AbstractGiven the elevated mortality of COVID-19 infections in older adults (Wu et al 2020), there is anurgent need to evaluate medicines that may prevent severe disease in these vulnerablepatients. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) wasreported to upregulate pan-antiviral gene expression and protect mice from a viral respiratorytract infection (RTI) (York AG et al. 2015). Importantly, RTB101 was also observed toupregulate interferon-stimulated pan-antiviral gene expression, decrease the levels ofinflammatory cytokines in serum, and decrease the incidence and severity of viral respiratorytract infections including coronavirus infections when given as prophylaxis during winter coldand flu season to older adults (Mannick et al. 2018, Mannick et al., 2019). Therefore wehypothesize that RTB101 will decrease the incidence and severity of COVID-19 when given asprophylaxis to older adults. Before undertaking a large well-powered trial for this indication, wepropose to undertake a pilot study to determine the feasibility of recruiting, consenting,screening and randomizing quarantined outpatient populations of older adults who are predictedto be at increased risk of developing COVID-19 (Specific Aim 1), assess whether COVID-19symptoms can be tracked using an eDiary in older adults (Specific Aim 2), and obtainpreliminary data on the incidence and severity of COVID-19 in subjects treated with RTB101 ascompared to placebo (Specific Aim 3). The data generated in the trial will be used to helpoptimize the study design of a larger adequately powered study to determine if RTB101 iseffective as COVID-19 prophylaxis in the older adults.References1. Mannick, J. B., Morris M, Hockey HP, Roma G, Beibel M, Kulmatycki K et al. (2018) TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 10, doi:10.1126/scitranslmed.aaq1564.2. Mannick et al, (abstract) IDWeek, 2019.3. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24.4. York AG, Williams KJ, Argus JP, Zhou QD, Brar G, et al. (2015) Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell. 163(7):1716-29.",2020,2024,RESTORBIO INC,659614,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase) | Prophylactic use of treatments,2019 +C03880,unknown,The role of serotonin signaling in the nucleus accumbens in excessive alcohol drinking,"PROJECT SUMMARY/ABSTRACTNeurological complications of SARS-CoV2 or Covid-19 have been reported in the literature but little is knownabout the extent to which neural systems are affected by this disease or the long-term impact on brain function.Alcohol consumption during the Covid-19 pandemic is on the rise due to factors such as unemployment, financialstrain, and loss of social support and may be a significant risk factor for neurological complications of SARS-CoV2. Other coronaviruses such as SARS-CoV are thought to gain entry to the brain via the olfactory bulb andquickly spread to interconnected regions such as the dorsal raphe nucleus (DRN), which is a major source ofserotonin (5-HT) neurons in the brain that orchestrates neurological functions ranging from autonomic control toemotional and motivated behavior. Alcohol is also known to compromise the function of 5-HT neurons in thebrain and may render them more vulnerable to infection by SARS-CoV2, exacerbating the neuropsychiatricsequelae of this disease. The goal of the present application is to determine whether alcohol can increaseexpression of known entry factors for SARS-CoV2 in DRN 5-HT neurons and facilitate infection of these neurons.In Aim 1, we will determine whether chronic intermittent alcohol exposure upregulates expression of entry factorsACE2 and TMPRSS2 in 5-HT DRN neurons that project to the olfactory bulb using retrograde tracers. In Aim 2,we will determine whether SARS-CoV2 can infect 5-HT DRN neurons via the olfactory bulb and whether chronicintermittent alcohol exacerbates infection and death of these neurons. Together, these studies will revealwhether alcohol is a significant risk factor for SARS-CoV2 invasion of the CNS and whether the DRN 5-HTsystems is a target for this infection.",2020,2022,UNIVERSITY OF IOWA,154500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2017 +C03881,unknown,Characterizing SARS-CoV-2 infection of human taste cells in culture,"AbstractRelatedness of Supplement Aim to Parent GrantIn the parent grant, we use cultured human taste (HBO) cells, pioneered at Monell by Co-Investigator HakanOzdener, to probe the metabolic sweet taste signaling pathway. HBO cells provide a useful model for probingtaste signaling in culture, but they have also been shown useful for investigating the pathophysiology of certainneurotrophic viral diseases (e.g. Zika virus; see Ozdener et al., 2020). Using HBO cells to accomplish theSupplement Aim will advance our understanding of the pathogenicity of SARS-CoV-2 and other viruses thatadversely affect taste and olfaction. Although many studies have reported taste and olfactory loss in individualswith COVID-19 disease, the underlying mechanisms and cellular effects in taste cells are not well understood.Due to changes in taste function in patients with COVID-19, it will be of particular interest to the parent grant toknow if the subset of sweet taste cells is susceptible to infection by SARS-CoV-2.",2020,2020,MONELL CHEMICAL SENSES CENTER,174487,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2015 +C03883,unknown,HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals: LC,"This proposal outlines the scientific agenda for the Leadership and Operations Center of the HIV VaccineTrials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4continents dedicated to developing globally effective vaccines for HIV, tuberculosis and now SARS-CoV-2.The HVTN has led HIV prevention science for over 20 years through robust phase 1 and 2 clinicaldevelopment trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizingmonoclonal antibody (mAb) VRC01 undergoing testing in 5 randomized controlled efficacy trials.With the rapid onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in thefield on the contribution of immune functions involved in preventing infection, in modifying COVID-19 disease,and in clearing viral infection. We believe the HVTN is well placed to study these gaps and rapidly deploy thisinformation in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study wepropose initiating an observational cohort study of approximately 400 persons in the United States (22 trialssites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a varietyof risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adultsbetween 18 and 55 years of age and those older than 55 years, and persons with high interest clinical orvirologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolongedviral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims ofthis study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, todevelop and qualify a suite of immunologic assays and reference reagents that will permit detailedinterrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in keypopulations and risk groups, and to characterize presentations of the infection among convalescent individuals.This initial study will tell us much about the adaptive immune responses in persons who have been infectedand recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfullyclearance of infection. It will improve our understanding of the dynamics and duration of responses, as well asthe epitope specificity and other defining signatures, and will inform rational design and testing of preventiveand therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork forprospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study willprepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.Laboratory, statistical and operational experience in this first trial will be invaluable preparation and priming ofnetwork machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVIDPrevention Network in coming months.",2020,2020,FRED HUTCHINSON CANCER RESEARCH CENTER,17799483,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America | Peru,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03884,unknown,SARS-CoV-2 testing at the Seattle Vaccine and Prevention CRS (30331),"Project Summary/AbstractOn March 11, 2020, the World Health Organization declared that the rapid spread of the novel coronavirus,SARS-CoV-2, and its associated disease, COVID-19, had become a global pandemic. The ongoing crisis calls for the involvement of clinical research sites (CRSs) to work rapidly and efficiently toward therapeutic andpreventative measures to control the epidemic. Our CRS, the Seattle Vaccine Trials Unit (VTU), has vast priorexperience conducting observational cohort studies and phase 1-2b clinical trials of preventative HIV vaccinesand other HIV prevention modalities. We propose bringing this infrastructure and experience to the field of SARS-CoV-2 clinical research. Our proposal is both to expand the scope of research activity at our CRS and to involvenew venues for protocol conduct. Onsite CRS activity will encompass natural history studies of recoveredCOVID-19 patients, as well as early to late phase vaccine protocols. New venues will be opened and developedin order to effectively conduct COVID-19 research with appropriate infection prevention procedures to preventSARS-CoV-2 transmission. Such new venues will include temporary structures that will provide capability toconduct clinical research in areas with continued SARS-CoV-2 transmission as specific areas with outbreaks arenoted during the course of the epidemic.",2020,2020,FRED HUTCHINSON CANCER RESEARCH CENTER,299401,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Vaccine trial design and infrastructure",2020 +C03886,unknown,Identifying host and viral correlates for coronavirus pathogenesis,"AbstractThe coronavirus (CoV) spike protein is a key viral determinant responsible for receptor binding andfusion/entry. The spike protein has also been predicted to be the major factor driving cross-speciestransmission, allowing the emergence of epidemic strains like SARS- and MERS-CoV. In the first decade afterSARS-CoV emergence, changes to the epidemic spike that allowed binding to a new host receptor werethought to underlie this zoonotic emergence. However, our work has shown that bat species already harborSARS-like CoVs with spike proteins capable of infecting human cells. These results argue that for a subset ofbat CoVs, receptor binding and infection of human cells is not the major barrier for emergence.We found that despite equivalent replication in vitro, chimeric viruses containing bat CoV spikes have reducedvirulence in vivo. Mice infected with a chimeric SARS-CoV expressing the bat derived SHC014-CoV spike hadreduced weight loss and lethality compared to SARS-CoV controls. Importantly, this attenuation occurs despiteequivalent replication to SARS-CoV in the lung. The results indicate that virulence is dictated by more thanjust the ability to infect host cells in vitro. Notably, we also found that the SHC014 spike chimera has reducedinfection of the large airways of the lung. These preliminary data shaped our central hypothesis that SARS-CoV virulence is predicated on both host interactions with and viral motifs in the CoV spike protein.Understanding the host and viral mechanisms that drive reduced airway infection may predict in vivopathogenesis and have critical implications for zoonotic emergence.In this proposal, we explore the host factors and CoV spike changes that attenuate the zoonotic SHC014 spikein vivo. In part one, we examine tropism changes finding that the zoonotic SHC014 spike has impaired upperairway infection. We predict that this incompatibility relates to differences in host protease activity. Wesubsequently define the specific host proteases that mediate this attenuation using both in vitro and in vivoapproaches. In part two, we use mouse-adaptation and structural analysis to predict spike changesresponsible for attenuation of the SHC014 spike. We subsequently generate mutant viruses and restore theSHC014 spike or attenuate the SARS spike in vivo. Finally, we evaluate the mechanism of attenuationfocusing on spike interactions with host proteases. Together, the proposal identifies host proteases and spikeinteractions that alter airway infection and dictate virulence following coronavirus infection. These findingsprovide critical insights for understanding virulence as well as have important implications for emergence andtransmission of coronaviruses.",2020,2024,The University of Texas Medical Branch at Galveston,497886,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +C03887,unknown,DEVELOPMENT OF A REGULATORY T CELL MIMETIC FOR TOLERANCE INDUCTION IN SKIN TRANSPLANTATION,"In this competitive revision we propose to formulate a second generation of regulatory T cell (Treg) mimetic byincluding adenosine (ADO) to the biomaterials system, from muxTIC (TGF-β1, IL-10, and CTLA-4Ig) tomuxTICA. The purpose is to investigate the mechanistic aspects of muxTICA as a locally-delivered (bronchialinstillation) therapeutic for acute respiratory distress syndrome (ARDS). We will test the capacity of thecombined immunosuppressive factors to skew alveolus macrophages to an anti-inflammatory phenotype in apro-inflammatory microenvironment. The experiments involve testing the agents in vitro using alveolarmacrophage lines, in human 3D airway epithelial tissues, and in a microfluidic shear cellular system.The rationale for exploring the immunosuppressive strategy is that COVID-19-induced ARDS is associatedwith excessive inflammation, characterized by rapid surges of pro-inflammatory cytokines such as IL-1β, IL-17,IL-6 and TNFα. The clinical picture akin to the cytokine storm immunopathology reported in the patientsinfected with the coronaviruses emerged in 2002 (`SARS"") and 2012 (""MERS"").Because corticosteroids arenot recommended and might exacerbate COVID-19-associated lung injury, novel immunosuppressivestrategies are urgently needed to mitigate the hyper-inflammation associated with ARDS.Clinical studies indicate that Tregs can ameliorate ARDS. Survivors of COVID-19 infections have higherblood-circulating Tregs than non-survivors, and patients with elevated TGF-β1 and IL-10 have betteroutcomes. Mechanistically Tregs limit lung fibrosis form infections and inhibit excessive virus-specific T cellresponses. A major driver of ARDS in COVID-19 infected patients is massive infiltration of macrophagesinfiltration, which produce pro-inflammatory cytokines and prorogate inflammation, resulting in lung fibrosis andalveolar edema. Tregs has the capacity to steer macrophages an M2 regulatory, anti-inflammatory phenotype.In addition to TGF-β1, IL-10, and CTLA-4Ig, another phenotype-defining factor of Tregs' immunosuppressiveeffects is ADO. In an animal model of ARDS, bronchial instillation of ADO reduces microvascular permeabilityin the lungs. Therefore, we will include ADO in the formulation to generate muxTICA.The experiments proposed are designed to advance an off-the-shelf immunosuppressant strategy as a logicalextension of the original specific aims in the context of an urgent medical need. Therefore, the studies in theoriginal and revision applications are conceptually and technologically synergistic and complementary.",2020,2021,DUQUESNE UNIVERSITY,47784,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03888,unknown,Cueing COVID-19: NLM Administrative Supplement for Research on Coronavirus Disease 2019,"PROJECT SUMMARYThe variability and the complexity of the data needed for clinical care requires clinicians to accurately andefficiently recognize COVID-19 amongst individuals, ranging from asymptomatic infection to multiorgan andsystemic manifestations. COVID-19, like sepsis, involves different disease etiologies that span a wide range ofsyndromes (e.g., initial, inflammatory, hyperinflammatory response). Because patients can present with mild,moderate, or severe symptoms, clinicians must both identify the disease stage and optimal treatment. Thefactors that trigger severe illness in COVID-19 patients are not completely understood. Like other complex,challenging diagnoses, clinicians in the trenches struggle to diagnose and treat patients using data available inthe electronic health record (EHR). In our current NIH NLM R01 ""Signaling Sepsis: Developing a Framework toOptimize Alert Design"", we created sepsis specific enhanced visual display models that outranked preferenceand performance when compared with the usual care of fragmented, non-directed information gathering. For thissupplement, we propose the design and development of COVID-19 diagnosis and clinical managementenhanced visual display models to support clinicians' recognition of critical phases in COVID-19diagnosis and treatment decisions. In order to create the models, we will identify relevant diagnostic andtreatment data elements that will include clinical characteristics, laboratory results, and radiology results (e.g.,chest CT). Our project will survey emerging models of COVID-19 and its stages, and ensure our models arecongruent with best practices that emerge as our knowledge as a medical community evolves. The modelsprovide an EHR based method to mine clinical data to identify the presence of COVID-19 which supports thevariety of ways in which COVID-19 presents, availability of data elements, accuracy of diagnostic tests, and thehighly infective nature of the disease. Specific Aim 1: To identify emerging patient-specific clinical features ofCOVID-19 and testing analytics to present critical information for COVID-19 diagnosis and clinical management.Elements include the characteristics listed above (e.g., symptoms, co-morbidities) plus COVID-19 specific testresults, including data specific to the tests' positive and negative predictive values. Specific Aim 2: To developan EHR embedded CDS tool using our COVID-19 enhanced visual display models using synthesized informationobtained through the NLM parent grant and Specific Aim 1. Evaluate the technical feasibility and usability of thenovel COVID-19 CDS tool. Why It Matters: During a pandemic, there's no room for ambiguity as clinicians arerequired to comb through the EHR. The ability to better visualize and interpret EHR data supports optimaldiagnosis and clinical management. Our enhanced visual display models will support clinicians as they evaluatedemographic factors, underlying conditions, and comorbidities that identify patients at higher risk of morbidityand mortality and will therefore drive better clinical management.",2020,2021,MEDSTAR HEALTH RESEARCH INSTITUTE,75000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Supportive care, processes of care and management",2020 +C03889,unknown,Novel delivery platform and antigen design for an effective COVID-19 vaccine,"PROJECT SUMMARY For effective management of the COVID-19 pandemic and its second wave, the design and implementationof multiple intervention approaches are crucial. They include the development of effective antivirals, high-affinitySARS-CoV-2-neuralizing human or humanized monoclonal antibodies, rapid diagnostic assays, immunogenicand protective vaccines, strategies to mitigate virus transmissibility, and enhancing capacity related to trainedmedical personnel, facilities, and supplies. Due to the possibility of antibody-dependent enhancement (ADE) ofCOVID-19, vaccine efforts should consider the use of a novel vaccine platform and design of a relevant antigenstrategy. It is essential to note that the elderly are the most vulnerable segment of the population that is at ahigher risk of COVID-19 severity; the vaccine development efforts should, therefore, consider the decline in theimmune competence in the elderly. We have developed a novel replication-defective (E1 & E3 deleted) bovine adenovirus (Ad) type 3 (BAd3)-based vaccine platform, which is better than the currently available Ad vector systems for providing heterologousinfluenza protection with dose sparing and is not impacted by the pre-existing human Ad vector immunity.Recently, we have revealed that the BAd vaccine platform provides the expression of significantly higher levelsof the immunogen and innate and adaptive immunity-related factors compared to that of human Ad vectors inmice. This work suggests that the BAd vector system could serve as an excellent delivery vehicle for thedevelopment of recombinant vaccines against emerging pathogens for the elderly and other segments of thepopulation. We have also identified a 22 amino acid residues Autophagy-Inducing Peptide (AIP) C5 (AIP-C5)from the CFP10 protein of M. tuberculosis that enhances robust T cell immune responses in mice to NP of H7N9influenza virus when delivered through an Ad vector. It conferred complete protection against H1N1, H3N2,H5N2, H7N9, and H9N2 influenza viruses. The proposal is based on the hypothesis that immunization with the autophagy-inducing replication-deficientBAd vector expressing relevant antigen/s of SARS-CoV-2 will strengthen an effective mucosal (lung) andsystemic anti-COVID-19 immunity. Under Aim 1, we will evaluate the immunogenicity and protectiveefficacy of a novel vaccine platform and antigen design in animal models for developing an effectiveCOVID-19 vaccine. Whereas under Aim 2, we will investigate the vaccine-induced antibody-dependentenhancement (ADE) of SARS-CoV-2 infection, the quality of memory innate, B and T cell responses, andthe durability of protective immunity in the best animal model. We believe that the use of a uniquenonhuman Ad vaccine platform and novel antigen design containing AIP-C5 will yield an effective COVID-19vaccine for all segments of the population. This effort will be of significant value to effectively flatten the COVID-19 pandemic's trajectory and its second wave.",2020,2025,PURDUE UNIVERSITY,792476,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +C03890,unknown,Remote COVID-19 Symptom Tracking and Improved Cancer Symptom Control for Cancer Patients at Home During the Pandemic,"PROJECT SUMMARYIn response to the COVID-19 pandemic, there is an opportunity to rapidly flex platforms for remote cancersymptom tracking and management to incorporate COVID-19 symptom monitoring and reinforce risk-reducingprecautions. It is critical for cancer patients at home to monitor early indications of COVID-19 symptoms, toadhere to mitigation strategies, as well as to manage their cancer-related symptoms so that they can decreasethe need to utilize the emergency department or unplanned hospitalizations for symptom care, which is acommon occurrence during cancer care. Remote monitoring adds a layer of home-based support which canbenefit all cancer patients and is not restricted to geographic proximity to oncology providers or distance from acancer center. Our Symptom Care at Home (SCH) system, utilized for our currently funded R01CA206522project to monitor and manage patient-reported (PRO) cancer symptoms, includes these necessary elements:remote PRO symptom monitoring, patient self-management information, and oncology provider (nursepractitioner) notification of symptoms exceeding pre-set thresholds. We propose adding two aims toR01CA206522 in response to PA-18-935 Urgent Competitive Revision to an Existing NIH Grant. The overallpurpose of this supplement is to describe the impacts of COVID-19 on cancer patients' well-being at home andevaluate, through a randomized clinical trial, if a systematic patient-reported outcomes (PRO) reportingprocess improves cancer care during a pandemic as compared to usual care. Specific Aims include: 1)describe patient-reported COVID-19 and cancer symptom trajectories over time, COVID-19 social distancingand hygiene practices, and COVID-19 related cancer treatment and daily living impacts on cancer patientsreceiving the SCH-COVID intervention and 2) compare the SCH-COVID intervention to enhanced usual careon health care utilization, COVID-19 diagnosis and outcomes, cancer treatment delays or changes, andpatient-reported global health, anxiety, mood, and feelings of social isolation.",2020,2021,UNIVERSITY OF UTAH,152500,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03891,unknown,Leveraging environmental drivers to predict vector-borne disease transmission,"PROJECT SUMMARYDesigning long-term control strategies to slow COVID-19 epidemics requires understanding theimpact of non-pharmaceutical interventions, their interaction with seasonal climate, and theireconomic costs. We developed an epidemiological model, based on an SEIR framework, thatcaptures non-symptomatic and symptomatic transmission and time lags between infection,hospitalization, and death, to explore the impact of non-pharmaceutical interventions. Weparameterized the model using publicly available data on biological rates and times and dailyCOVID-19 death data from two California Bay Area counties. We estimated that the basicreproduction number, R0, ranges from 2.6-4.3, and that current shelter-in-place orders havereduced the effective reproduction number, Re, below one. In this project, we will use the modelto: 1) estimate transmission parameters and the impact of social distancing on long-term controlstrategies for every county in California; 2) understand the interaction between climateseasonality and control interventions; and 3) study the socio-economic factors underlyingepidemiological disparities across California counties, and the economic costs and benefits ofintervention strategies. This research will help to guide public health responses to the COVID-19crisis and develop safe and effective exit strategies from stay-at-home orders.",2020,2024,STANFORD UNIVERSITY,52568,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Approaches to public health interventions | Policy research and interventions,2019 +C03892,unknown,Characterization of Misinformation Dynamics in COVID-19 related health information in online social media,"Abstract:Social media has become predominant as a source of information for many health care consumers. Howeverfalse and misleading information are a pervasive problem in this context. Specifically, during CVID-19 pandemic,misinformation has been a significant public health challenge, impeding the effectiveness of public healthawareness campaigns and resulting in suboptimal responsiveness to the communication of legitimate risk-related information. In the proposed research, we will apply our ""Pragmatics to Reveal Intent in Social Media(PRISM) framework to facilitate automated detection of intent and belief attributes underlying COVID-19 relatedmisinformation. The PRISM framework aims to incorporate and integrate communication intent, semantics andstructure of online communication to study social processes and cognitive factors underlying misinformationcomprehension. Such analysis forms the foundational step towards characterization of misinformation seedingand perception in digital social settings, ultimately allowing us to develop scalable and reliable computationalinfrastructure that can help formulate resilient and effective dissemination approaches to negotiatemisinformation spread, easing public health burden and informing policy regulations as needed.",2020,2021,The University of Texas Health Science Center at Houston,63106,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Social impacts | Other secondary impacts,2020 +C03893,unknown,Extended follow-up of randomized participants in the INSIGHT START trial,"PROJECT SUMMARYINSIGHT is serving as lead clinical trials network for the development of a master protocol fortrials of therapeutic neutralizing monoclonal antibodies (nMAbs) for patients hospitalized withCOVID-19. Two NHLBI networks, PETAL and CTSN, the ACTG and Veterans Administrationare collaborating with us on the development of the master protocol and will enroll patients inthe trial we lead. The master protocol has been reviewed by CSRC and, following that review,the protocol will be submitted to the FDA.There are many nMAbs to study and we anticipate rolling different treatments into this trial overthe next 2 years. We anticipate the first nMAb to study will be available to begin the first trial inJuly 2020. This grant supplement will be used to support the INSIGHT SDMC, 4 INSIGHTICCs. It will also support subcontracts with our central specimen repository (ABML) and a drugdistribution company (PCI Pharma).",2020,2024,UNIVERSITY OF MINNESOTA,4517512,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Protocol,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase),2020 +C03895,unknown,Tuning big data analysis infrastructure for HIV research,"SummaryThe COVID‐19/SARS‐CoV‐2 pandemic is a once in a generation, ""all‐hands‐on‐deck"" event for thescientific community. This pandemic is also the first in which real time genomic data are available,e.g. via GISAID [1], where genomic sequences are deposited daily. Vital insights about the virus andthe epidemic depend on rapid and reliable genomic analysis of diverse viral sample sequences bymultiple laboratories. Yet we repeatedly encounter the same avoidable shortcomings early in viralinvestigations, including COVID‐19: lack of reproducibility, rigor, and data/analytic sharing. Onlyabout 10% of the published genomes have quality metrics, primary data (read files), or any level ofdetails on analytics, making these data irreproducible and unverifiable; over 40% of GISAIDsubmissions to date provide no information about how the sequences were generated. Essentialquestions about the extent of intra‐host genomic variability (indicative of adaptation or multipleinfection), viral evolution (selection, recombination), transmission (phylogenetic andphylogeographic) cannot be answered reliably if researchers cannot trust/replicate the source dataand analytical approaches. One of the key goals/deliverables of this supplement will be the openanalytic workflows that can be used to curate and standardize genomic data, and high qualityannotated variation data.",2020,2022,PENNSYLVANIA STATE UNIVERSITY-UNIV PARK,374737,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C03897,unknown,Administrative Supplements for Coronavirus Disease 2019 (COVID-19) Research,"ABSTRACTCOVID-19 is caused by a suspected zoonotic source of Severe Acute Respiratory Syndrome-Coronavirus-2(SARS-CoV-2). While coronaviruses (CoVs) are relatively common, mutations can cause severe symptoms inhumans; the challenges of SARS-CoV-2 are: the long incubation period (2-14 days, median 5.1 days), high viraltiter which can appear while a COVID-19+ patient is asymptomatic, and the long period of time in which it isviable outside of its host, both airborne and on surfaces. It is estimated as of May 28, 2020, that there are over5.7 million cases in 212 countries. Symptoms can range from mild to severe and may include: fever, coughing,shortness of breath, sore throat, fatigue, congestion, and chills. Of those cases, 13.8% require medicalinterventions, with 6% of patients dying Tragically, there are no available vaccines against SARS-CoV-2. Witha wide range of clinical symptoms and more importantly a large population of asymptomatic COVID-19+ patients,a crucial question regarding genetic susceptibility, i.e. whether human leukocyte antigens (HLA) play a role inthe patient symptomology. Preliminary in-silico data have revealed binding affinity of specific HLAs to SARS-CoV-2 antigens, indicating a genetic HLA association with COVID-19 clinical symptoms, which is the primaryobjective of this application. We hypothesize that ""A certain HLA allele or combination of certain alleles canserve as biomarker for the severity of COVID-19"". To test this hypothesis, we propose to define HLA bindingepitopes from dominant SARS-CoV-2 T cell antigens using in-silico analysis (Aim 1), determine the HLAalleles of symptomatic and asymptomatic of COVID-19 patients using whole genome genotyping (Aim2), and examine the T cell function in correlation with HLA-associated disease protection andsusceptibility (Aim 3). The results are expected to provide a broader understanding of the genetic HLAassociation pertaining to the severity of COVID-19. Additionally, results should provide critical measures inperforming HLA typing and virus detection to identify high risk individuals. Utilizing this finding, we may be ableto prevent transmission and mitigate the impact of this disease in our dental, health care personnel, and otherfront-line professionals who are particularly susceptible to aerosol or droplet virus transmission.",2020,2021,UNIVERSITY OF FLORIDA,225011,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +C03898,unknown,Administrative Supplement to The When to Worry about Language Study (W2W-L),"PROJECT SUMMARY - Original SubmissionPrimary language impairment (PLI) begins early in life and affects 6-8% of children. Although languageintervention is maximally effective the earlier it is delivered, normative variation in language acquisition acrosstoddlerhood (here 24-36 months) impedes accurate identification of PLI prior to late preschool age. Theproposed study introduces a novel, theoretically- grounded, neurodevelopmental framework designedto generate a sensitive and specific model to identify PLI as early as possible. Our developmentally-sensitive, translational approach introduces multiple innovations including: (1) characterizing thedevelopmental patterning of toddler emergent language beginning at 24 mos. using state-of-the-art methods,within a large community sample; (2) incorporating EEG/ERP neural biomarkers of language into PLI riskassessment; (3) using a novel paradigm to assess the protective effects of both behavioral and neuralsynchronization within parent-child language transactions; and (4) consideration of irritability, a robustdevelopmental marker of early mental health risk, to enhance identification of those language delayed toddlersat highest risk for persistence. For the proposed When to Worry about Language Study (W2W-L), wecapitalize on our funded study of 350 infants (50% irritable and 50% non-irritable) (R01MH107652, Wakschlag,PI) and enrich it via recruitment of a sub-sample of 200 late talking toddlers. This will yield a large and diversesample of 550 24-month-olds. Our key predictors will be toddler emergent language patterns (24-36 months),their neural biomarkers and synchrony within the transactional language environment. Our central outcome isprimary language impairment (PLI) status at preschool age (54 mos., when PLI can be reliably evaluated),assessed via clinical gold standard expressive and receptive language abilities. SPECIFIC AIMS: AIM 1a.Evaluate accuracy of PLI prediction based on multi-component measures of language including intensivelongitudinal assessments of toddler developmental precursors of key language functions at older ages, neuralbiomarkers. We will assess neural and linguistic processing via quantitative EEG during parent-child interactionand ERPs to speech sounds as well as during eye tracking tasks and 1b. Evaluate feasibility of creating analgorithm for early identification of PLI that can be applied in clinical practice, using cross-validation andmachine learning. AIM 2: Test the hypothesis that parent-child dyadic synchrony buffers PLI risk For the firsttime, we combine behavioral and novel social EEG measures of parent-child synchrony during naturalinteraction and a custom-designed word learning task to directly test how observed (behavioral) and neural(EEG) dyadic synchrony impact word learning. AIM 3: Test whether consideration of toddler irritabilityenhances PLI prediction. In sum, PLI confers sustained negative effects on a variety of personal-social andacademic outcomes. Pinpointing children at highest risk for PLI is critical for reducing the public health burdenof PLI for children, families, and the systems supporting them, and enhancing targeted allocation of resources.",2020,2023,NORTHWESTERN UNIVERSITY,197084,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Therapeutics research, development and implementation",Disease susceptibility | Pre-clinical studies,2018 +C03899,unknown,Homebound with Dementia in the Context of COVID-19,"Homebound with Dementia in the Context of COVID-19Summary/AbstractIndividuals with dementia live for many years at home in the community. Even though the community is theoverwhelming preference for site of care, the experience of living with dementia in the community is challengingfor patients and their caregiving families. In the existing parent grant, we examine how being homebound impactsthe lived experience of individuals with dementia using the longitudinal, nationally representative National Healthand Aging Trends Study and the companion National Study of Caregivers with linkages to Medicare claims, theU.S Census, and other geographic data. In this supplement, we examine the impact of COVID-19 on homeboundadults with dementia and their caregiving families in the epicenter of the pandemic, New York City. Usingroutinely collected data within the Mount Sinai Health System, we will examine change in care delivery forhomebound patients during COVID-19 outbreak in NYC, compare end-of-life care experiences for homeboundpatients and caregivers before, during, and after the COVID-19 pandemic, and conduct an in-depth analysis ofcare disruptions for homebound patients with dementia during COVID-19. In summary, this project will criticallyenhance our understanding of the lived experience of patients with dementia by examining their experienceaccessing care throughout this pandemic. Prior to the onset of COVID-19, homebound older adults with dementiafaced social isolation and routine challenges to accessing healthcare. Patients are highly reliant on familycaregivers for daily support.1 In the wake of this pandemic, there are tremendous and unprecedented challengesfor these individuals and their caregivers who support them. The proposed study will allow for the firstdocumentation of the homebound experience before, during, and after the peak of COVID-19 infections in NewYork City and will set the stage for new guidelines and research into emergency preparedness, programadaptations and partnerships with community organizations for persons living with dementia in the communityand their caregiving families.",2020,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,423728,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C03900,unknown,Alabama Clinical Trials Unit - Administrative Supplement: SARS-CoV-2 Testing,"Program Director/Principal Investigator (Last, First, Middle): Overton, Edgar TurnerAbstract:The Alabama CRS is intimately involved in the response to the Alabama COVID-19 epidemic. Our researchteam is currently involved in multiple components of the local response, including COVID-19 testing fordiagnosis, antibody testing for epidemiology and for the development of therapeutic and preventive therapies,contact tracing of COVID-19 patients, outpatient and inpatient management of COVID-19 patients, employeehealth initiatives to prevent COVID-19 among our healthcare workers, expanded testing in the community(particularly to marginalized populations), providing education both within our institution and to the outsidecommunity, as well as leading research initiatives in the state of Alabama. In our efforts to flatten the curve andmitigate COVID-19 disease in our state, we desperately need additional resources, including additional staffing,additional testing capacity for both PCR and antibody testing, and reagents to complete that work. Thissupplement provides our team the very resources needed to achieve these aims.For this proposal, we will augment our ongoing efforts with the following projects. We are adding two nursepractitioners to our team. With their level of experience, they will assist with several aspects of the proposal,including expanded testing in community and for research studies, identifying acute and convalescent patientsto perform both PCR testing and blood draws to facilitate an understanding of viral kinetics, as well as theevolution of host responses in COVID-19 patients. The data and virologic and serologic samples will provide keyinsight in to the distribution and natural history of COVID-19 among both rural and urban settings in Alabama.Additionally, these data will inform a greater understanding of the host-viral interaction and host factors thatcontribute to severity of disease. Currently, we have very little testing being performed outside of the urbancenters and have very little understanding of our rural areas.Dr. Heath has partnered with Dr. Barbara Van Der Pol and her molecular diagnostics lab to increase testingcapacity for our institution and Alabama, at large. Their laboratory team have the capacity to perform anadditional 200 PCR tests per day. We will leverage this laboratory infrastructure to enhance testing forpopulations that are unable to come to testing sites in our urban centers. In addition, Dr. Heath's lab hasexpanded capacity to develop sensitive, specific antibody testing approaches to characterize the natural historyof disease, and more importantly to identify donors for life-saving plasma donation. These initiatives will alsoinform the search for surrogates of protection among convalescent COVID-19 patients and the search forvaccine-elicited immunity, as well as monoclonal antibodies.OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page",2020,2020,UNIVERSITY OF ALABAMA AT BIRMINGHAM,300000,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03901,unknown,A Sensing Platform for Rapid at Home-Test of COVID-19,"ABSTRACTSince the first case of COVID-19 was reported in the United States (U.S.) on January 21st, 2020, ithas already been ascertained to affect >900K active cases with >50K deaths. Currently, COVID-19is being diagnosed primarily by three techniques, i.e. reverse-transcription polymerase chainreaction (RT-PCR), gene sequencing and chest computed tomography (CT). However, limitationsof sample collection and transportation, as well as kit performance with inadequate access toadvanced instrumental techniques, often cannot report COVID-19 at its initial presentation leadingto the spread of this infectious disease to a wider community. Moreover, researchers found at leastthree central variants, distinguishable by amino acid changes, among 160 different complete humanSARS-CoV-2 genome sequences. This limits the universal applicability of the currently availablecommercial COVID-19 kits. In this proposal we present a novel approach for screening of activeCOVID-19 cases with a paper based lateral flow assay mediated colorimetric POC biosensor thatwould be able to detect the SARS-CoV-2 gene sequence using specifically designed antisenseoligonucleotides (ASO). This unique approach for selective sensing of SARS-CoV-2 eliminates thepossibility of misinterpretation arisen due to the genomic variants of SARS-CoV-2 which is the mostconcerning limitation of the current COVID-19 sensing kits.",2020,2021,UNIVERSITY OF MARYLAND BALT CO CAMPUS,76500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2019 +C03902,unknown,A Highly Specific Point-of-Care Rapid Real-time Sensing Device for COVID-19,"ABSTRACTSince the first case of COVID-19 was reported in the United States (U.S.) on January 21st, 2020, it has alreadybeen ascertained to affect >900K active cases with >50K deaths. Currently, COVID-19 is being diagnosedprimarily by three techniques, i.e. reverse-transcription polymerase chain reaction (RT-PCR), genesequencing and chest computed tomography (CT). However, limitations of sample collection andtransportation, as well as kit performance with inadequate access to advanced instrumental techniques, oftencannot report COVID-19 at its initial presentation leading to the spread of this infectious disease to a widercommunity. Moreover, researchers found at least three central variants, distinguishable by amino acidchanges, among 160 different complete human SARS-CoV-2 genome sequences. This limits the universalapplicability of the currently available commercial COVID-19 kits. In this proposal we present a novel approachfor screening of active COVID-19 cases with an electrochemical quantitative biosensor. This unique approachfor selective sensing of SARS-CoV-2 eliminates the possibility of misinterpretation arisen due to the genomicvariants of this virus which is the most concerning limitation of the current COVID-19 sensing kits. Weanticipate that our sensor can detect the specific target nucleic acid sequences without signal cross talk witha detection limit to be around 50 fg/ml with time of response to be around 2-3 mins.",2020,2021,UNIVERSITY OF MARYLAND BALT CO CAMPUS,70380,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2019 +C03903,unknown,Social Media Intervention to Promote Smoking Treatment Utilization and Cessation among Alaska Native Smokers,"PROJECT SUMMARYThis application is for an administrative supplement (PA-18-591) to NIDA-funded R34 grant ""Social MediaIntervention to Promote Smoking Treatment Utilization and Cessation among Alaska Native Smokers"" (R34DA46008). It is responsive to the NIDA notice of special Interest, NOT-DA-20-047 and meets the statedobjective to understand the broad impacts of COVID-19 (e.g., anxiety, social isolation) on access to addictiontreatment and substance use. The parent R34 grant is a Stage I treatment development grant to develop andpilot test a Facebook (FB) intervention for AN smokers statewide. With the advent of the COVID-19 pandemic,now more than ever, virtual options, such as social media, hold promise as sustainable and scalableintervention strategies to promote access to smoking cessation treatment among Alaska Native (AN) people,and other vulnerable and underserved health disparity groups who experience a disproportionate burden oftobacco-related morbidity/mortality and who may also be disproportionately affected by COVID-19. In thissupplement, we propose to adapt and evaluate perceived effectiveness of new content for the FB interventionrelevant to COVID-19 and smoking, using a rigorous participatory approach, as was done in developing othercontent. We will also collect data on self-reported impacts of COVID-19 on our outcomes of treatmentutilization and cessation within our ongoing pilot clinical trial. Our Specific Aims (within the scope, timeline, andcurrent evaluation process of the current R34) are to: 1) Assess the perceived effectiveness of social mediacontent and communication on COVID-19 and smoking (N=40). We will use existing content on COVID-19(e.g., CDC Tips™ campaign videos) for adaptation. Potential content adaptations for COVID-19 messagingthat may impact treatment utilization and quitting as barriers or facilitators include stress, anxiety, perceivedrisks, social isolation, and social support; and 2) Explore the self-reported impact of COVID-19 perceived risks,severity, and COVID-related anxiety, stress, financial impacts, social isolation, and social support, on ourprimary outcome of smoking treatment utilization and cessation in our ongoing R34 pilot clinical trial (N=60) at6-months follow-up. Our measures have been pilot tested and were selected from a bank of COVID-19measures provided by the NIH. Expanding FB intervention content to address COVID-19 and evaluatingCOVID-19 impacts, within the parent R34 grant, is timely and significant. This work will provide the foundationfor a larger Stage II efficacy trial.",2020,2021,MAYO CLINIC ROCHESTER,77895,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts | Social impacts | Economic impacts,2018 +C03904,unknown,Immunogenicity and Efficacy of SARS-CoV-2 stabilized prefusion Spike protein vaccines in infant rhesus macaques,"ABSTRACTThe emergence of the highly-transmissible novel coronavirus SARS-CoV2 has led to a global pandemic ofsevere respiratory disease. While elderly individuals and adults with co-morbidities are high risk populations,coronavirus disease (COVID-19) can occur in individuals across all age groups, including infants. Therefore, itwill be important to develop a vaccine that can be administered in early life and generate long term immunity toend the COVID19 pandemic. While initial safety testing of vaccine candidates will occur in adult populations,there are many potential advantages of targeting the vaccine to the pediatric vaccine schedule including highrates of pediatric vaccine coverage and potential for lifelong immunity. In fact, infants can respond remarkablywell to protein antigens, including the hepatitis B and candidate HIV envelope vaccines, and there is evidencethat HIV-infected infants are better equipped to generate HIV-neutralizing antibodies. Moreover, our previouswork in human and rhesus monkeys has established that infants are able to generate HIV Env vaccineresponses of comparable or higher magnitude to that of adults that persist for months and are able to beboosted. The parent grant P01 AI117915-06 ""Early Life Vaccination to Prevent HIV Acquisition in Adolescence""aims to assess candidate HIV envelope mRNA and SOSIP trimer vaccines in infant rhesus monkey nonhumanprimate model and determine their efficacy against HIV acquisition in adolescence. As related complementarystudies, we propose to assess the immunogenicity and efficacy of candidate SARS-CoV2 spike (S) protein andmRNA vaccine candidates in infant rhesus monkeys. We hypothesize that infants can mount effective andpersistent systemic and mucosal antibody responses to SARS-CoV-2 vaccination that will protectagainst virus challenge. This work will provide preclinical safety, immunogenicity, and efficacy data onleading SARS-CoV2 vaccine platforms that can de-risk human trials in pediatric populations and justifybypassing time consuming and expensive age de-escalation studies. The end of the SARS-CoV2 pandemicwill require high global coverage with a vaccine that prevents viral spread and generates long lasting immunity,which may best be achieved with a pediatric targeted vaccine.",2020,2022,DUKE UNIVERSITY,1227827,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +C03905,unknown,MECHANISMS OF AXON GUIDANCE IN LARYNGEAL REINNERVATION FOLLOWING INJURY OF THE RECURRENT LARYNGEAL NERVE,"Project SummaryLaryngeal functional impairment after critical illness and laryngeal intubation trauma are underrecognized. This impairment will become an issue of epidemic proportions as the number of intubated ICU patients has dramatically increased due to COVID-19. To date, 85,000-170,000 patients with COVID-19 have required ICU admission with intubation for ventilation. Their laryngeal injury risk is exponentially increased due to the current national guidelines which recommend delaying tracheotomy for COVID-19 patients until they have been intubated >21 days. This is alarming as tracheotomies are usual performed at 7-10 days and 57% of patients evidence laryngeal mucosal injury after just 12 hours. These injuries, caused by pressure of the endotracheal tube on laryngeal structures, can permanently compromise vocal function, create glottic incompetence and generate posterior glottic stenosis. All have major morbidity and quality of life sequelae and no optimal treatments exist. Voice dysfunction leads to frustration, isolation, fear, and altered self-identity, as well as impaired quality of life, lost worker productivity, and the need to file disability claims at rates similar to those of chronic diseases like congestive heart failure, chronic obstructive pulmonary disease and severe depression. Quality of life consequences from voice disorders due to treatment of COVID-19 patients in the ICU is expected to be extremely prevalent and severe, resulting in a high personal and societal burden. Our long-term goal is to develop interventions to reduce the incidence and impact of post-intubation laryngeal injury. Heightened risks in the COVID-19 population make it imperative that we understand the burden of laryngeal injuries and learn from this pandemic to minimize risks for future intubated patients. The aims of this project are: 1. Create a national cohort of COVID-19 ICU survivors and quantify the acute burden of infection and treatment on laryngeal function, voice, communication and quality of life after hospital discharge, 2. Quantify the longer-term burden of COVID-19 infection and treatment on laryngeal function, voice, communication and quality of life within the cohort, 3. Identify potential intervention targets to prevent and treat post-intubation related laryngeal injuries. Building on our previous work and the power and reach of the North American Airway Collaboration which we developed, with over 40 participating academic institutions, we will conduct a longitudinal COVID-19 ICU survivor cohort study. The study will gather clinical data on 500 patients as well as longitudinal outcomes obtained using laryngoscopy and validated patient reported outcome measures evaluating voice (Voice Handicap Index-10), communication (Communication Participation Item Bank) and global quality of life (12-Item SF Health Survey).This research will broadly impact the fields otolaryngology, anesthesiology and critical care medicine. It will advance our knowledge of intubation related injuries and allow us to better prevent and treat them, ultimately decreasing patient morbidity and the societal burden of this disease.",2020,2024,COLUMBIA UNIVERSITY HEALTH SCIENCES,233752,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,Data Management and Data Sharing,,,United States of America,,Epidemiological studies | Clinical characterisation and management,"Disease surveillance & mapping | Supportive care, processes of care and management | Post acute and long term health consequences",2019 +C03906,unknown,A nanobody-based vaccine strategy to combat CoVID-19,"SummaryThe development of a vaccine that protects against SARS-CoV-2, the coronavirus responsible for the currentpandemic (COVID-19), is urgently needed. We have developed camelid-derived antibody fragments -nanobodies - that target surface proteins on mouse and human antigen presenting cells. These targets includeclass II MHC products and the integrin alpha M (CD11b). By attaching to these nanobodies various antigens inthe form of proteins or peptides, we can elicit stronger B and T cell responses against the attached payloadswhen compared to the corresponding 'free' antigens. In particular, adducts composed of the anti-CD11bnanobody with peptides of viral origin induced a protective cytotoxic CD8 T cell response in a humanpapillomavirus model and inspire confidence that a similar outcome may be accomplished for SARS-CoV-2. Wepropose to apply these strategies to generate strong adaptive immune responses against SARS-CoV-2 antigens.The anti-mouse and anti-human class II MHC-specific nanobodies recognize all allotypes and will be used totarget antigens to mouse and human class II MHC products in normal and HLA-DR4 transgenic mice. CD4 Tcell and antibody responses will be analyzed in these studies. Adducts composed of the CD11b nanobody andCOVID-19 antigenic peptides will be used to elicit CD8 T cell responses in normal and HLA-A2 transgenic mice.For the most immunogenic SARS-CoV-2 antigens, we shall identify the minimal peptides recognized for possibleinclusion in future vaccine preparations.",2020,2021,BOSTON CHILDREN'S HOSPITAL,442500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C03907,unknown,"Electrokinetic paper diagnostic platform: 15-minute, quantitative nucleic acid amplification for viral pathogens in whole blood","ABSTRACTCOVID-19 is a severe respiratory tract infection caused by the newly discovered, and highly contagious, SARS-CoV-2 virus that emerged in late 2019 in Wuhan, China and has infected over 3 million people globally (> 1MUS) and has caused over 215,000 deaths (58,000 US). SARS-CoV-2 RNA is the only sensitive and specificbiomarker for diagnosis of an active COVID-19 infection and is diagnosed by reverse-transcription polymerasechain reaction (RT-PCR) in a central virology lab. Several CLIA-waived NAAT systems have been rapidlyadapted for testing COVID-19, and have been granted the Emergency Use Authorization (EUA) for use at thepoint-of-care; however, their use is generally restricted to clinical sites because of the instrument, and/or protocolcomplexity, and high cost associated with the equipment. Self-administered nasal swabs have been shown tobe an effective sample to detect COVID-19, and as a result the FDA is allowing their use as an acceptablespecimen for COVID-19 laboratory testing, paving the way for home-based COVID NAT tests.We currently have a NIBIB project focused on the development and validation of a paper microfluidic based POCNAT for quantifying HIV Viral load from whole blood. Here, we propose to leverage this on-going effort to developa COVID-19 Nucleic Acid Amplification Self Test (COAST) that can be performed at home to detect COVID-19infections based on SARS-CoV-2 RNA. COAST is fully disposable test will detect as little as 5,000 cp/swab,have a COGS of less than $2.50, and will have sample-to-result within 30 minutes. In this proposal, our primaryobjectives are (1) optimizing and validating a sensitive and specific Recombinase Polymerase Amplification(RPA) isothermal amplification assay for the N-gene for SARS-CoV-2 RNA with lateral flow readout and (2)developing and evaluating the COAST home-based test with integrated sample preparation, isothermalamplification, lateral flow read-out. RPA is a low-temperature, isothermal amplification chemistry that canspecifically detect a target with a wide range of genomic diversity and easily be integrated with LFA read-out.COAST has a novel elution tube, self-regulating positive temperature coefficient heaters, on-paper RPAamplification, and LFA readout. The RPA assay will be validated with de-identified SARS-CoV-2 RNA fromCOVID-19 patient samples collected by UWs Virology Lab and the COAST cartridge will be evaluated usingmock nasal swabs with non-infectious targets.COVID-19 self-testing can drastically increase total testing numbers which can improve state and federal publichealth officials understanding of disease proliferation, as well as informing policy response (e.g. stay-at-homeorders, school closures, etc.) and allocation of emergency response (for example distribution of PPE orventilators). Self-testing can also reduce new infections by initiating prompt quarantine and public health contacttracing, especially in the case of asymptomatic or mildly symptomatic patients.",2020,2021,UNIVERSITY OF WASHINGTON,413677,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C03908,unknown,Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies,"Project Summary SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >4.1 million people,including >240,000 deaths. Though COVID-19 pathology in children is believed to be relatively mild comparedto adults, approximately 10% of infants experience severe COVID-19 illness requiring advanced care, andrecently, a possible link has been reported between COVID-19 and a serious inflammatory disease recentlytermed ""Pediatric Multi-System Inflammatory Syndrome Temporally Associated with COVID-19"" (1-4).Furthermore, as COVID-19 symptoms do not appear to correlate with transmissibility, infants and youngchildren are likely responsible for a significant amount of SARS-CoV-2 dissemination (5-7). Clearly, protectingthis population from infection remains essential. One potential mechanism of protection in babies is the passiveimmunity provided through breastfeeding by a previously-infected mother, and if the SARS-CoV-2 antibody(Ab) response in milk is potent, these Abs may be highly beneficial as a COVID-19 therapeutic. These milk Absmay be effective in treating COVID-19 by providing secretory (s) IgA and sIgM Abs, the major Ab componentsin milk. Abs of the s class are resistant to proteolytic degradation and likely highly functional in respiratorytissue (2, 6). Nearly all sIgA/sIgM in milk is derived from the mucosal immune system, including the respiratorytract; therefore, we should expect a SARS-CoV-2-reactive sIgA/sIgM response, though the magnitude,functionality, and durability of this response remains unknown. As such, SARS-CoV-2-reactive milk Abs mustbe comprehensively studied for their potential therapeutic and protective efficacy. Towards that aim, we haverecruited over 1600 lactating participants, including over 600 who have recovered from COVID-19 illness. Ourpilot data using 15 samples found 93% obtained post-COVID-19 contain SARS-CoV-2-reactive sIgA Abs.Based on this early evidence, our proposed project intends to: (a) Measure the SARS-CoV-2-reactive Abs inmilk following infection and the long-term durability of this response; (b) Determine the neutralization capacityof these Abs; and (c) Evaluate the non-neutralizing, Fc-mediated functionality of these Abs. Thiscomprehensive research will determine if COVID19-specific Abs in milk have protective biologic functions andshould be considered as a source of therapeutic Abs. These data would provide a foundation for 'convalescentmilk Ab' efficacy studies, and have implications beyond the pandemic, serving to fill a relatively largeknowledge gap regarding human milk immunology.",2020,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,793353,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03909,unknown,System Biological Analyses of Innate and Adaptive Responses to Vaccination,"ABSTRACTThe recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) pandemicposes a major global health challenge. Coronavirus disease (COVID-19) is caused by SARS-CoV-2 and represents the causative agent of a potentially fatal disease. Science has moved veryrapidly in isolating, sequencing, and cloning the virus, and developing diagnostic kits, within amatter of weeks. However, major knowledge gaps remain about the dynamic interaction betweenthe human immune system and the SARS-CoV-2. In particular, several fundamental questionsregarding its pathogenesis, and the mechanisms of protective immunity that need to be inducedby vaccination, remain unanswered. Learning how the immune system senses SARS-CoV-2infection and orchestrates protective immunity is critical for designing effective vaccines andtherapeutics. Our previous work using systems biology, multi-omics approaches to analyzeimmune responses to vaccination in humans has delineated molecular signatures of innateimmunity to vaccination and infection and have provided rich mechanistic insights into the immuneresponse1-7. In this proposal, we propose a site-specific study to analyze samples from theIMPACC sub-study performed at Emory. We will use an integrated multi-omics approach (singlecell transcriptomics, metabolomics, single cell epigenomics) to study innate immunity to COVID-19 infection in humans. We will obtain PBMCs and tracheal aspirate samples from the IMPACCsub-study that will be conducted at Emory. We will address the following questions: What are themolecular and cellular signatures of the immune response to COVID-19 infection in the blood andtracheal aspirates of infected subjects? Does COVID-19 infection exert an epigenetic imprint ofinnate immunity? What is the molecular landscape and function of myeloid cell subsets and airwayepithelial cells in the healthy lung, and following COVID-19 infection? These questions will beaddressed in the following specific aims: 1) Determine the single cell transcriptional andepigenetic landscape of the immune response to COVID-19 infection in blood and trachealaspirates, and 2) Determine the molecular identity and functions of myeloid cell subsets andepithelial cells in human lung and their response to COVID-19 infection. These studies will providesignificant insight into the human immune response to COVID-19 infection that can be leveragedfor designing vaccines and therapeutics to prevent or treat the infection.",2020,2021,EMORY UNIVERSITY,7425306,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C03910,unknown,Clinical studies of a bionic pancreas for automated glucose management in cystic fibrosis-related diabetes mellitus,"Project SummaryRecent data suggest that diabetes is common in patients hospitalized with severe COVID-19 illness, andhyperglycemia during hospitalization has been associated with poor outcomes in this patient population. As withother infections, ensuring good glycemic control will be important for optimizing the care of patients admitted withCOVID-19; however, frequent glucose monitoring is time consuming, requires donning of personal protectiveequipment (PPE), and exposes healthcare workers to infection. The Dexcom G6 Continuous Glucose Monitoring(CGM) System provides real-time glucose data every 5 minutes and is approved for use in patients ages 2 andolder in the outpatient setting. The FDA has recognized the potential value of using CGM to allow hospital staffto remotely monitor glucose in inpatients with COVID-19, releasing a statement that they will not object if CGMcompanies provide devices and technical support to hospitals who want to implement CGM for glucosemonitoring to support COVID-19 healthcare efforts. Using the Dexcom G6 to monitor patients' glucose levelsremotely in real-time could significantly improve diabetes management by alerting providers to high or lowglucose values, reducing the burden of frequent in-person fingerstick glucose checks, limiting viral exposure ofhealthcare providers, and conserving PPE. However, given the lack of data confirming the accuracy of this devicein the hospital setting, particularly in critically ill patients with COVID-19, the introduction of this technology intoclinical use in the hospital and ICU setting requires a systematic approach to evaluate accuracy and safety priorto widespread use.We have developed a plan for introducing the Dexcom G6 into clinical use at Massachusetts General Hospital(MGH), using iterative quality assurance processes and comprehensive data collection to ensure safety andefficacy in this population. This will provide timely, real-life data to guide other health care organizations in theuse of this technology during the COVID-19 crisis. In this proposal, we will pursue the following three aims: (1)we will establish the accuracy of the G6 CGM in patients admitted in an ICU and on a medical floor, identifyingfactors that may impact CGM accuracy and instituting a calibration protocol to improve accuracy if needed; (2)we will investigate the feasibility of non-adjunctive use of the Dexcom G6 in critically ill and non-critically illpatients admitted with COVID-19; and (3) we will evaluate the safety and efficacy of the Dexcom G6 inhospitalized patients with COVID-19 in a nested case-control study of patients with diabetes admitted to MGH.The data collected in this proposal will provide critical information guiding Aim 3 of the parent grant, whichproposes to study an artificial pancreas device, the bionic pancreas (BP), in patients with cystic fibrosis relateddiabetes. Similar to those with COVID-19, patients with CF are often hospitalized with respiratory compromise,hypoxia, and hemodynamic instability. The BP utilizes the Dexcom G6 for glucose monitoring, so acquiring dataon the accuracy and performance of the Dexcom G6 in hospitalized COVID-19 patients would be very valuablefor informing this aim of the R01.",2020,2023,MASSACHUSETTS GENERAL HOSPITAL,224611,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2019 +C03911,unknown,Enhanced infectivity of SARS-CoV-2 in Particulate Matter exposed Sinonasal Epithelial Cells,"Program Director/Principal Investigator (Last, First, Middle): Ramanathan, Murugappan JrIt is estimated that while the majority of SARS-CoV-2 infections in the ongoing coronavirus disease-2019(COVID-19) pandemic are asymptomatic or have mild symptoms, hospitalizations and mortality largelyoccurs in patients with co-morbid conditions such as obesity, diabetes and COPD. Our understanding ofthe role of environmental exposures in modifying the response to SARS-CoV-2 is emerging and airpollution, smoking and vaping have been associated with worst outcomes of SARS-CoV-2 patients. Thereis a time sensitive urgent need to understand host defense mechanisms in the sinonasal epithelia whichare compromised due to environmental exposures and may increase susceptibility to SARS-CoV-2infection. This administrative supplement will forge collaboration with an expert in SARS-CoV-2 research toexpand our horizon in this critical area. We will test the hypothesis of targeting a host defense pathwaywhich is compromised in air pollution that may protect and modify the response to SARS-COV-2respiratory infection. Through the parent R01 grant, we have demonstrated that chronic exposure to PM2.5has an overarching role in epigenetic reprogramming. Our studies have established that transcription factorNuclear factor erythroid-factor 2 (Nrf2) is a key activator of anti-oxidative, anti-inflammatory, and innateimmune defenses. We and others have demonstrated in human biospecimens and animal models thatchronic exposure to PM2.5 causes a decline in Nrf2 activity that correlates with compromised innateimmune defenses. In mice deficient for Nrf2 (Nrf2-/-), viral and bacterial infection causes oxidative stress,worsened lung inflammation, acute lung injury and greater mortality compared to wildtype mice. Genetic orpharmacological activation of Nrf2 pathway can rescue these effects. Disruption of Nrf2 pathway has beenshown to cause upregulation of angiotensin-converting enzyme 2 (ACE2) which is the functional receptorfor SARS-CoV2 entry into airway epithelial cells. Furthermore, hypomethylation of the ACE2 gene hasbeen demonstrated to increase ACE2 expression in immunocompromised patients. The goal for thisadministrative supplement (in response to NOT-AI-020-031) is to investigate the crosstalk of airpollution exposure, host defense and SARS-CoV-2 infection. If this pilot project is successful,preclinical testing of Nrf2 activators will provide proof of concept for further development a noveldrug target for prevention and treatment of SARS-CoV-2 infection. The proposal will leverageexpertise of our team on air pollution, respiratory diseases and an expert virologist with ongoing BSL-3SARS-CoV-2 research. Successful completion of this project will provide proof of concept for future studiesdirected towards development of a novel strategy of targeting host defense for prevention and treatment ofSARS-CoV-2 infection in susceptible populations.",2020,2020,JOHNS HOPKINS UNIVERSITY,196500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease susceptibility",2020 +C03912,unknown,High Precision System Analysis of Infant Immune Responses,"Project Summary/AbstractThe COVID-19 pandemic is a worldwide emergency causing major social and economic disruptions. As anemergent viral infection, there are major knowledge gaps regarding COVID-19. In particular, there is limitedinformation thus far on the impact of COVID-19 on pregnant women and their infants. Initial studies suggest thatclinical manifestations during pregnancy are similar to those identified in non-pregnant adults, and recent reportshave described cases of severe pneumonia and ARDS in pregnant women. Information on the impact of maternalinfection on the infant is also limited. Investigators in China documented perinatal transmission in a small numberof newborn infants. A common feature of severe COVID-19 appears to be inflammation, which is a known riskfactor for poor pregnancy outcomes and can impact the development of the infant immune system.Thus, there is an urgent need to understand the role of COVID-19 during pregnancy and its impact on the infant.Our Parent U01 is focused on high-resolution analysis of immune responses in healthy infants. The goal of thissupplement is to determine how maternal COVID-19 infection affects the infant immune system, which we willachieve by analyzing the interplay between the maternal and infant immune systems in the context of COVID-19. We hypothesize that COVID-19 during pregnancy leaves a stable imprint on the infant immune systemdefined by enhanced inflammation and dysregulated responses to vaccines. Although our focus is the analysisof infant immune responses, a comprehensive system analysis approach is required to efficiently identify themost relevant immunologic and virologic factors that determine COVID-19 outcomes in pregnant women, andhow they impact the immune responses of the fetus and the infant. We propose conducting a prospectivelongitudinal study in pregnant women with COVID-19 occurring at any time during pregnancy and follow theirinfants longitudinally to assess their immune responses until 7 months of age. As a reference control, we willinclude a cohort of non-COVID-19 pregnant women and their infants.",2020,2022,RESEARCH INST NATIONWIDE CHILDREN'S HOSP,360758,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03913,unknown,DIFFERENTIATION AND FUNCTION OF MONOCYTES AND MACROPHAGES,"Project SummaryAlthough much remains unclear with respect to the pathogenesis of COVID-19, the possibilities that cytokinestorm and altered coagulation contribute to adverse disease pathogenesis have emerged. Both the cytokineoutput and promotion of coagulation may be mediated by activated monocytes. Monocytes, for instance, arethe central leukocyte in blood to express tissue factor (F3) and initiate coagulation and this activity promotescomorbidity in Ebola and HIV infections. One cytokine that seems most notably elevated in plasma of COVIDpatients is IL-6. In keeping with the potential importance of IL-6 in cytokine storm, our preliminary data revealthat blood monocytes, of all subsets, are a major source of IL-6 in COVID leukocytes and that their productionof IL-6 positively correlates with adverse disease progression. Surprisingly, though monocytes producecytokines, other features of canonical activation were not present in monocyte subsets of COVID patients.Particularly, induction of functional tissue factor in IL-6-producing monocytes was minimal to absent. This wasin striking contrast to control monocytes from healthy subjects treated ex vivo with LPS or resiquimod. Giventhe clinical concern that coagulation may be altered in COVID-19 and contribute to pathogenesis of adversedisease and given the very robust expression of IL-6, we were especially surprised that tissue factor was notinduced. Overall, it appears that the stimulus for activation of monocytes in COVID-19 patients is distinct fromcanonical responses that also induce tissue factor in cytokine-producing cells, or perhaps a subset ofmonocytes able to activate the tissue factor pathway is missing or in extracted COVID-19 PBMCs. Theoverarching aim of this work is to define, using a robust longitudinal dataset, whether proinflammatoryactivation of monocyte subsets in blood associates with disease severity and to define the core characteristicsof such activation. We will also carry out exploratory analyses in search of signals that lead to such activation.A key resource for our proposal is access to a bank of frozen PBMC, serum, plasma and whole blood in whichlongitudinal blood draws are being collected on 300 COVID-19 patients of differing disease severity admitted toBarnes Jewish Hospital. This bank has been established by the Institutional Clinical and TranslationalResearch program at Washington University School of Medicine. Resources from this bank will be coupledwith a stock of frozen PBMCs from >50 control participants in our laboratory and PBMCs from HIV subjects,where the state of monocyte activation will be compared with that of monocytes derived from COVID patients.",2020,2020,WASHINGTON UNIVERSITY,164107,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03914,unknown,Evaluation of the FcgR mechanisms in the antibody-dependent enhancement of SARS-CoV-2 infection,"AbstractGiven the uncontrolled spread of SARS-CoV-2 and the devastating impact on public health, therapeuticinterventions are urgently needed for disease control. Indeed, several biotech and academic groups are currentlyfocusing their efforts on the isolation and clinical development of monoclonal antibodies (mAbs) with potentneutralizing activity against SARS-CoV-2. During the past few weeks, a number of neutralizing anti-SARS-CoV-2 mAbs have entered clinical testing, representing promising therapeutic modalities for the control of COVID-19disease. In parallel, several vaccine candidates are currently in clinical development or testing, aiming to providelife-long immunity against SARS-CoV-2. However, a major safety concern for these approaches has been thepotential of antiviral IgG antibodies to enhance, rather than control, infection; a phenomenon termed as antibody-dependent enhancement (ADE). Although ADE has been primarily demonstrated for flaviviruses, like dengue, itis unknown whether this phenomenon also extends to coronaviruses, like SARS-CoV-2. Previous studies onSARS-CoV suggest that IgG antibodies against the Spike protein may promote infection of leukocytes andmodulate disease severity by triggering acute lung injury through excessive or inappropriate activation of pro-inflammatory pathways. This pathogenic activity is proposed to be mediated through the interaction of their Fcdomains with FcγRs expressed on the surface of effector leukocytes. Given the ongoing clinical developmentefforts for antibody-based therapeutics and vaccines to control SARS-CoV-2 infection, it is important to assesswhether anti-SARS-CoV-2 antibodies have the capacity to mediate ADE and if so, determine the precisemolecular mechanisms and the role of FcγRs in this process. A major obstacle in the study of human Fc functionin vivo is the substantial interspecies differences in the FcγR biology between humans and other mammalianspecies, necessitating the development of novel animal strains that recapitulate the unique complexity of humanFcγR structural and functional attributes. To overcome these limitations, the proposed studies aim to developnovel mouse strains and hamster models of SARS-CoV-2 infection, which will be used to systematically evaluatethe in vivo pathogenic activity of a panel of anti-SARS-CoV-2 mAbs and polyclonal IgG antibodies from recoveredCOVID-19 patients. By comparing the capacity of Fc-engineered mAbs with defined FcγR binding profile tomediate ADE of SARS-CoV-2 infection, the proposed studies will provide novel insights into the in vivo ADEactivity of anti-SARS-CoV-2 IgG antibodies, characterizing the precise FcγR pathways that contribute to diseasepathogenesis.",2020,2023,ROCKEFELLER UNIVERSITY,654116,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2020 +C03915,unknown,Inflammatory cytokines and pyroptosis in Coronavirus infection,"SUMMARYHuman Coronaviruses (hCoV) cause severe respiratory syndromes like SARS, MERS, and the ongoingpandemic of Covid-19 caused by the recently identified SARS-Cov2. Human and murine studies indicate thatexcessive inflammation, rather than viral replication, may precipitate these infections into lethal diseases. Theoverarching hypothesis of this proposal is that the excessive inflammation and neutrophil recruitmenttriggered by IL-1β and pyroptotic cell lysis severely impair the host ability to control infection and maintainhomeostasis. The corollary of this hypothesis, if proven correct, is that carefully timed inhibition of IL-1β,pyroptosis, and neutrophil proteases should be beneficial to treat Covid-19 and other hCoV infections.Increasing the significance of our study, these therapies are already approved to treat a number of humandiseases, a fact that bodes well for a rapid approval to treat Covid-19 and other hCoV infections. The mouseCoV MHV-1 provides an excellent model of CoV lung infections and will be used to test our hypothesis inthese specific aims: AIM 1. Is IL-1β deleterious during CoV infection and through which mechanisms? We willtest the hypothesis that excessive production of IL-1β drives neutrophil recruitment to the infected lung withconsequent tissue damage. The ability of IL-1β to exacerbate the pathogenesis of MHV-1 lung infection willbe studied in susceptible and resistant mouse strains treated with pharmacological inhibitors of IL-1β or instrains deficient in IL-1β. We will determine whether excessive neutrophil recruitment damages lung tissuethrough release of neutrophil elastase. We will also test the hypothesis that IL-1β inhibits type I and type IIIIFN production by stimulation of PGE2 synthesis. We will use genetic and pharmacological approaches toexamine how inhibition of PGE2 production affects IFN-I and IFN-III production during MHV-1 infection. Wewill test whether interventions to regulate IFN-I or PGE2 in the early or late phases of the infection haveopposite effect on the disease outcome. AIM 2. Is pyroptosis beneficial or deleterious in MHV-1 infection andwhich inflammasome triggers cell death? We will test the hypothesis that gasdermin D-dependent pyroptosisof lung cells may affect pathogenesis of coronavirus infection in opposite ways by either restricting viralreplication or exacerbating inflammation. We will test the hypothesis that pyroptosis of CoV-infected lungepithelial or endothelial cells is mediated by caspase-11. Mouse strains that lack expression of caspase-11 inlung epithelial or endothelial cells have been generated in our lab and will be used to test tissue-specific roleof caspase-11 during MHV-1 infection.",2020,2022,Rosalind Franklin University of Medicine and Science,429000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03916,unknown,Mapping Immune Responses to CMV in Renal Transplant Recipients - Mechanistic Assays Core (UCSF),"ABSTRACTThe COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significantmorbidity and mortality in previously healthy patients. A significant observation is that although this infectionmay result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patientsexperience progression of respiratory symptoms to requirement of intubation for mechanical respiratorysupport and death due to severe respiratory failure. This clinical observation strongly suggests that differencesin host immunologic response are the determinative factor in clinical outcome. We hypothesize that theproposed systems immunology, biostatistical and computational modeling approaches, coupled with detailedclinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplaybetween SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess thefrequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonalityof their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immuneresponse to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation-based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resourceof highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development ofnovel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.",2020,2021,University of California-Los Angeles,208861,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C03917,unknown,Complex Odor Recognition of the Main Olfactory Bulb,"PROJECT SUMMARYCOVID-19 is a devastating disease caused by the severe acute respiratory syndrome coronavirus clade 2(SARS-CoV2) that has resulted in 100,442 deaths in the U.S. (May 28th, 2020). Smell loss is a major symptomfor COVID-19 (1-4). In a recent publication we identified TRPM5-expressing cells (microvillous cells (MVCs)and olfactory sensory neurons (OSNs)) as viral-responding cells in the olfactory epithelium (OE)(5). MVCs arepart of a family of TRPM5-expressing cells found in the airways and the intestine that respond to virus, bacteriaand irritants with a type 2 immune response through IL-25 and release of acetylcholine (6, 7). In preliminarystudies we find that intranasal herpes simplex virus type 1 (HSV-1) infection in mice elicits a dramatic shift inTRPM5 expression from MVCs to the basal epithelium consistent with activation of stem cells (SCs) forimmune defense, as proposed for chronic inflammation of the OE (8-10)expressionHowever,inflammationIt is unclear whether this increasedand altered location of TRPM5 is an aberrant response, contributing to persistent inflammation.influenza infection increases TRPM5 expressing cells in the lung, leading to damaging persistent(11) Here.. we hypothesize that SARS-CoV-2 infection of OE upregulates TRPM5expression, leading to proinflammatory cytokine release, decrease in OSN numbers and activity,persistent inflammation yet ineffective viral clearance leading to worse COVID-19; whereas addition ofTRPM5 blockers will attenuate cytokine release and viral loads.Weepithelialflufenamicwill test this hypothesis with studies of changes in inflammation and olfactory function in human olfactorycell cultures infected with by inhibition of TRPM5 using the FDA approved drugacid in two specific aims:SARS-CoV2Aim 1. Determine if activation of the TRPM5 transduction cascade in MVCs mediates the inflammatoryresponse to SARS-CoV-2 viral infection leading to loss of olfactory function.Aim 2. Determine if TRPM5 expression in the OE promotes SARS-CoV-2 neurotropism, facilitatingnervous system disease.",2020,2023,UNIVERSITY OF COLORADO DENVER,194375,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",1988 +C03918,unknown,Vaccine and Treatment Evaluation Units,Summary/AbstractThe Emory VTEU has proven essential in the fight against the pandemic. This supplement will allow for furtherinvestigations into Treatments trials (20-0006) and Vaccines trials (20-0003 and Moderna Phase III) againstCOVID-19.1,2020,2022,EMORY UNIVERSITY,7831958,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C03920,unknown,Administrative Supplement Covid19: Molecular Regulation of B cells and T cells in Human SLE,"The COVID19 pandemic illustrates the urgent need for understanding human B cell responses to emergentpathogens and its application to assessing herd immunity. Our laboratories have described the phenotypic,immunological and molecular features of different arms of human B cell responses and in particular, the originalcharacterization of the human extrafollicular effector B cell activation pathway and its contribution to differentmemory and plasma cells responses. On that basis, we we propose to interrogate the different arms of the B cellresponse to the SARS-CoV-2 virus; to identify the B cell compartments that participate in the early, ongoing andlate post-infection responses; and to determine their contribution to the establishment of herd immunity, at leastin part through the generation of protective B cell memory. The latter is an essential feature that could beuncoupled from the persistence of serum antibodies; and therefore, would go unrecognized unless formallytested. We postulate that the establishment of cellular B cell memory and the ability to evaluate its magnitudeand quality will be critical to track the risk of the population to short-term re-infection and seasonal exposure; todesign vaccines capable to trigger this protective feature; and to develop SARS-CoV-2 B cell-based diagnostictests. These goals will be accomplished using blood samples from SARS-CoV-2-infected and convalescentindividuals through the following specific aims: Aim 1. Characterization of SARS-CoV-2-specific B cellresponses through multidimensional B cell flow cytometry A precise adjudication of the cellular origin,magnitude, and persistence of the anti-SARS-CoV-2 B cell response will be accomplished by antigen-specificflow cytometry and validated by multiplex antigen assays and single cell analysis of the B cell populations. Aim2. Measurement of SARS-CoV-2-specific B cell memory and herd immunity. Phenotypic features andantigen-specific flow cytometry assays established in aim 1, will be applied to intermediate and late post-infectiontime points in order to understand: a) the cellular compartments in which SARS-CoV-2-specific B cell memoryresides; b) its quality, magnitude and distribution within the population; c) its provenance (whether from early oflate cellular precursors); and d) its concordance or conversely, uncoupling from serological responses and thegeneration of long-lived plasma cells (LLPC).",2020,2023,EMORY UNIVERSITY,525608,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03921,unknown,Consortium for Immunotherapeutics against Emerging Viral Threats,"ABSTRACT We recently galvanized the Coronavirus Immunotherapeutic Consortium, CoVIC, an international effortto conduct side-by-side analyses of leading therapeutic antibody candidates against the SARS-CoV-2 Spikeprotein contributed by a range of large and small companies and academic labs on multiple continents. CoVICprovides an opportunity for side-by-side analysis of the leading therapeutic candidates under the same assayconditions, as well as real-time collaborative assembly of a broader, deeper dataset on the activities andpotencies of antibodies against SARS-CoV-2 than could be assembled by any single discovery effort alone. Thecurrently funded CoVIC studies focus largely on characteristics of the Fab region of the IgG therapeutic: bindingand mechanical neutralization, and analyze only spike from the original Wuhan reference strain of SARS-CoV-2. The proposed supplement will provide support for critical components that are currently missing from CoVICbut which are needed to accelerate clinical advancement of antibodies that will be safe, efficacious and offerdurable protection. We will determine Fc-mediated activities of the therapeutic antibodies, the likelihood or riskof enhancement from clinical candidates, and which epitopes and sites of and susceptibility to mutagenic escape.The resulting body of information will inform early and next-generation antibody therapies and will ensure thattherapeutics are known which are responsive to emerging viral variants.",2020,2022,LA JOLLA INSTITUTE FOR IMMUNOLOGY,2688763,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C03922,unknown,Mechanisms of T Cell Memory Quiescence,"ABSTRACT (COVID-19 SUPPLEMENTAL RESEARCH) During fast-spreading disease outbreaks (such as the present COVID-19 pandemic), quick induction ofherd immunity through vaccination is critical. Currently there are many SARS-CoV2 candidate vaccines invarious stages of clinical development, aimed at inducing robust multimodal protective immunity comprisingboth long-lived antibody and memory T cells. However, we have little control over how quickly protectiveimmunity may be established following immunization. At the very minimum, vaccine-induced T cells require aperiod of ~20-30 days of antigenic rest after initial immunization to effectively downregulate their effectorprogram and convert into quiescent, functionally potent, long-lived memory cells poised at portals of pathogenentry. If vaccine-induced T cells are re-exposed to antigen during this mandatory rest period - as might occurin case of exposure to virulent pathogen during an outbreak - the quantity, quality and overall protectiveefficacy of immune memory are significantly jeopardized. Hence, shortening the window of immune memorydevelopment is a key goal during vaccination, and is of high significance during pandemics to establishaccelerated protection in frontline healthcare and essential service providers, and speed up herd immunity inthe general population for expedited return to normalcy and economic growth.In this administrative supplement, we will evaluate candidate immunomodulatory strategies to accelerate andenhance vaccine-induced protective T cell memory to SARS-CoV2 by facilitating Treg-aided effector-to-memory conversion. This work is based on our studies establishing a critical role of Tregs in promotingeffector-to-memory conversion through CTLA4, an inhibitory molecule most highly expressed on Tregs(amongst all immune cells) (Immunity, 2015). Importantly, soluble CTLA4 administered in trans, is alone ableto fully supplement the function of Tregs in memory differentiation, and accelerates the formation of protectiveanti-viral immunity by promoting the metabolic switch necessary for effector-to-memory conversion. Theseproof-of-concept studies in models of viral immunity (conducted under the aegis of past R21, and parent R01awards) lay a strong foundation for enhancing SARS-CoV2-specific immune memory following immunizationwith candidate SARS-CoV2 vaccine in preclinical murine model. These studies represent a naturaltranslational extension of the parent R01 focused on mechanistic and molecular details of Treg-dependentmemory enhancement through CTLA4 in model viral infections. Importantly, CTLA4-Ig is FDA-approved PhaseIII drug - ready for clinical translation. Therefore, immediate impact on our ability to quickly establish herdimmunity against SARS-CoV2 is expected. In addition to addressing the current COVID-19 exigency, thesestudies are also relevant to other pandemics and situations of urgent vaccination of our defense troops forquick deployment to disease endemic areas.",2020,2023,SEATTLE CHILDREN'S HOSPITAL,338479,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03923,unknown,Immunoprotective Properties of Tissue-resident Memory T Cells in Mice and Humans within Mucosal Sites,"PROJECT SUMMARYThis is an emergency competitive revision to our existing R01 AI121129. As part of this parent R01 entitled,""Immunoprotective properties of tissue-resident memory T cells in mice and humans within mucosal sites"", weperform longitudinal sampling of the genital skin and HSV-2 lesions for both viral load as well as cytokine levels.This approach was highlighted in our recent paper in the Journal of Clinical Investigation (Roychoudhury et al,2020, PMID 32125285), in which we show that T cell-derived proteins including interferon gamma and granzymeB surge concurrently with local viral load. We now propose to use this successful approach to a second infectiousdisease, SARS-CoV-2.The COVID-19 pandemic is an unprecedented event in modern human history, with morbidity and mortality ratesdangerously high in the elderly and those with medical comorbidities. Given the current pandemic status, themost urgent goal is to lower case fatality and hospitalization rates. Front line providers need reliable tests torapidly triage infected patients according to severity and effective therapies to treat them. There is reason forhope; the mean time between presentation and need for hospitalization is a week for SARS-CoV-2 infectedpatients, which allows a much longer window to intervene than for influenza infection; clinical trials are alreadyassessing various small molecular agents and neutralizing antibodies. Thus, the goals of this application are touse an existing prospective cohort to assess multiple potential biomarkers of progression to severe disease atinitial clinical presentation, identify immunologic variables associated with viral elimination over ensuing weeks,and model the optimal timing, dose and duration of therapeutic interventions to prevent respiratory failure. Wewill leverage the currently surging local epidemic in Seattle; an IRB-approved protocol which is already enrollinginfected outpatient participants; a wide network of referring providers; and our multi-disciplinary team ofclinicians, T-cell immunologists, and mathematical modelers, who have existing, complementary tools andexisting collaborations, to rapidly produce and analyze critical data. We will share our results openly and in realtime with the international scientific community to assist in managing this global emergency.",2020,2021,FRED HUTCHINSON CANCER RESEARCH CENTER,817238,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C03924,unknown,Characterizing COVID-19 Patients through a Community Health Information Exchange and EHR databases,"Project Summary/AbstractThe COVID-19 pandemic is a significant public health problem that will require novel approaches formanagement and intervention. Knowledge of the disease's transmission, symptomatology, clinicalcourse, treatment and outcomes is rapidly evolving based on many sources. An important source foradvancing this knowledge are data from electronic health records (EHR) and health informationexchanges (HIE) because they can provide a real-time, unvarnished view of the disease. However,the initially ""invisible"" nature of the disease makes clear that clinicians and public health personnelwere at a significant disadvantage in discovering and quantifying the pandemic. There is an urgentneed to learn rapidly from EHR and other data to improve discovery and monitoring of patientsinfected by the coronavirus. The evolving dynamic and understanding of the incidence and course ofCOVID-19 requires that we develop new methods for discovery from data. The long-term goal of ourresearch is to develop collaborative filtering algorithms to facilitate access to and analysis of clinicaldata. The goal of this application is to characterize COVID-19 patients through data in a communityHIE, specifically the Indiana Network for Patient Care (INPC) within Indiana's HIE (IHIE), andunderstand how that characterization differs from that within the EHRs of individual health systems.Understanding how COVID-19 patients are represented in HIEs and EHRs will build an importantfoundation for downstream computational activities, such as real-time discovery, public healthsurveillance, intervention management and contact tracing. The two specific aims of this project areto (1) extract a cohort of patients suffering from COVID-19 and similar diseases from IHIE and (2)characterize patients according to several dimensions, such as demographics, signs and symptoms,and disease course using both the INPC as well as separate EHR data sets. The data, going back to1/1/2015, will be extracted from the INPC, and the clinical data warehouses at IU Health andEskenazi Health, two of our major health system partners. As of this writing, 230,749 individuals inIndiana (3.4 percent of the population of 6.73m) have been tested for the coronavirus, of whom32,078 (13.9 percent) have tested positive. We will apply computational phenotyping approachesusing both HIE and individual EHR data in order to help us evaluate to what degree data fromindividual EHRs can help approximate characterizations based on HIE data. This proposal issignificant because it will help us understand how HIE and EHR data can be used to characterizeboth COVID-19 and non-COVID-19 patients. It is innovative because it leverages multiplecomputational phenotyping methods on both individual organizations' EHR, as well as HIE, data togenerate a comprehensive characterization of COVID-19 and non-COVID-19 patients.",2020,2021,Indiana University - Purdue University Indianapolis,74999,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2020 +C03925,unknown,A high-throughput nanoparticle assay to characterize cancer neoepitope-specific T cells,"PROJECT SUMMARYAs of early May 2020, there have been approximately 3.7 million confirmed cases of COVID-19 infectionworldwide, and approximately 260,000 deaths.1 A retrospective cohort study of patients from Wuhan, Chinademonstrated that although both survivors and non-survivors initially follow similar clinical courses, developingsepsis and acute respiratory distress syndrome (ARDS) at similar time points, non-survivors progress on tomulti-organ failure (MOF), secondary infection, and death.2 Additionally, pediatric cases have been shown tohave a much milder disease course than adults, and the reasons for this are not clear.3These differences inclinical courses could in part be explained by the patients' pre-existing T cell repertoire, phenotype, and HLA-specificity, which may influence downstream T cell phenotype and cytokine responses. Using in silicoapproaches, we identified multiple potential T cell epitopes which can be divided into 3 broad categories: 1)Epitopes with homology to the original SARS virus 2) Epitopes with homology to other viruses/bacteria 3)Epitopes with homology to self-antigens. We have developed aAPC constructs to interrogate both HLA class Iand HLA class II CD8+ and CD4+ T cell responses, respectively. As such, we will be able to obtain a broadunderstanding of the role these 3 different types of virus-specific epitopes play in the development of COVID-19 specific responses. A better understanding of how T cells contribute to progression of disease severity isespecially pertinent to patients who are on long-term immunosuppressive therapies because of malignancies,bone marrow transplant, or organ transplant. Patients with cancer were found to have higher probabilities ofhaving more severe disease and worse outcomes in China than both patients without cancer and cancersurvivors.4This proposal builds upon previously published work to screen patients for virus-specific T cellsusing only 100 L of whole blood, and with a turn-around time of less than 24 hours.5 In addition, we have alsodeveloped an enrichment and expansion (E+E) technology to rapidly expand virus and tumor-specific T cellswithin a 7 day time frame.6-12Combining these two approaches, we will identify clinically important T cellepitopes and demonstrate that functional T cells can be expanded to large numbers over a brief period-of-timein otherwise healthy donors and patients with cancer.",2020,2021,JOHNS HOPKINS UNIVERSITY,163750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility,2020 +C03926,unknown,Toward a protective Covid-19 vaccine utilizing an established vector platform,"AbstractThe recently emerged coronavirus SARS-CoV-2, the causative agent of COVID-19, is rapidly spreading in theworld with over 4,8 million cases, and 320,000 deaths as of May 16, 2020. This novel coronavirus is thought tohave emerged from a live animal market in Wuhan, China. It has quickly spread in the community with largeclusters of human-to-human transmission. Sequencing of several isolates has determined that the most closelyrelated strains are SARS-like bat coronavirus lineages. The susceptibility of SARS-CoV-2 to anti-viralcompounds, its ability to replicate in cell lines or host factors regulating its replication are all currently unknown.Importantly, there are no therapeutics available to treat the virus, although investigational studies are underway.Modelling of the current outbreak suggests that the virus could infect >1 billion people and become a yearlyepidemic. Identifying people who have developed antibodies is important for the epidemiology as well as patientcare.With the exponentially expounding threat of SARS-CoV-2 to global health, a vaccine is desperately needed.Herein we propose the development of a novel, highly efficacious and safe COVID-19 vaccine with facile scaleup potential. Our proposal uses a rabies virus-based vector that has proven to be an efficient vaccine againstemerging and re-emerging infectious diseases. We have demonstrated that inactivated rabies virus particlescontaining the coronavirus (CoV) spike S1 protein induce potent immune responses and provide protection inanimal systems against Middle Eastern Respiratory Syndrome coronavirus (MERS) and Severe AcuteRespiratory Syndrome (SARS) coronavirus, both of which are highly related to SARS-CoV-2. A similar vaccineentitled CoraVax™ is available and herein we propose to analyze CoraVax™ immunogenicity in mice as well asits abilty to protect in a hamster model.",2020,2022,THOMAS JEFFERSON UNIVERSITY,429000,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies,2020 +C03927,unknown,The Molecular Regulation of Horizontal Basal Cell Activation in the Olfactory Epithelium,"Project SummaryOlfactory dysfunction, including anosmia, is an unexpected and unexplained consequence of infection by the b-coronavirus SARS-CoV-2 and can be the sole manifestation of COVID-19. Existing bulk and single cell RNAseq datasets demonstrate that a very low percentage of nonneuronal cells - sustentacular (Sus) cells, horizontal basal cells (HBCs), and Bowman's gland and duct (BG/D) cells - of the olfactory epithelium (OE) express ACE2, the high affinity receptor for SARS-CoV-2, and the viral relevant proteases, TMPRSS2, FURIN and CATHEPSINS B and L. However, the lack of protein expression data prevents definition of which types and what percentage of cells are susceptible to infection. Specific Aim 1 proposes immunohistochemical evaluation of our library of human and mouse olfactory mucosa (OM) for the presence of the corresponding proteins using validated antibody markers for OE cell types and viral-relevant proteins. The inclusion of mouse allows us, first, to assess protein expression during OE regeneration, and, second, makes feasible subsequent experiments examining the interaction of virus with the olfactory periphery, whether in normal mice or ones that are made transgenic for hACE2, offering a humanized animal model and greatly enhancing our understanding of the disease. For example, other b-coronaviruses reach and decimate the CNS after intranasal inoculation even though olfactory sensory neurons (OSNs) do not express the relevant receptors (Schwob et al, 2001). Even if Aim 1 demonstrates that a substantial percentage of non-neuronal cells express the machinery necessary to support infection and replication, the mechanism underlying the diminution/elimination of the sense of smell would remain obscure. Hence, Specific Aim 2 proposes the pathological examination of the impact of COVID-19 on the human OM and olfactory bulb (OB) in patients that die of the disease and come to autopsy at Massachusetts General Hospital, which Autopsy Service has agreed to supply us with these tissues. This Aim takes advantage of the PI's expertise in general anatomic pathology, and more specifically that of the diseased olfactory epithelium and bulb as well as the contributions of Dr. Eric Holbrook, co-I of this competitive revision, who will harvest the mucosa and assist in the analysis of the tissue. Besides conventional pathological assessment, the tissue will be interrogated for the presence of active virus, the type and extent of inflammatory infiltrate, and the loss of the various cell populations of the epithelium and bulb. The results will clarify whether and to what extent SARS-CoV-2 transits the OSNs and the olfactory nerve and damage the CNS as do other b-coronaviruses. Finally, Specific Aim 3 proposes high risk-high reward experiments based on our ability to differentiate the OE cell types from activated HBCs in vitro, which will then be assayed for the protein apparatus underlying infection and compared with the in vivo results obtained in Aims 1 and 2. When the Aims are completed successfully, the field will then be poised to begin the virological investigations in vitro and in vivo that will truly explain why olfactory dysfunction is such a hallmark of COVID-19.",2020,2025,TUFTS UNIVERSITY BOSTON,223840,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03928,unknown,Bioinformatics Framework for Wastewater-based Surveillance of Infectious Diseases,"Project Summary SARS-CoV-2 is now a global pandemic with 4.2M cases and 290K deaths worldwide (as of May 12, 2020).In the United States, there are over 1.3M cases and 81K deaths. Locally, Arizona has over 11K cases and 562deaths. In response to this public health emergency, several studies have been published that describepatient characteristics in terms of signs, symptoms, and clinical endpoints. In addition, epidemiologists andinfectious disease researchers have utilized next-generation sequencing technology to produce completegenomes of the virus for clinical and epidemiologic investigation. Genomic epidemiology has enabled scientiststo understanding localized transmission while determining geographic sources of introductions from differentstates and countries. However, most of the sequencing for SARS-CoV-2 (as well as for other viruses) isperformed outside of state or local health departments such as the Centers for Disease Control and Prevention(CDC), universities, or private labs. It can then be difficult to link the pathogen, once sequenced, back to thedata collected by the health department for case investigation. This can inhibit genomic epidemiology whenthere is no link between sequences of viral isolates and epidemiologic case data. There is limited research in how to link pathogen sequences to epidemiologic case data; especially forCOVID-19. Thus, despite the abundance of clinical and epidemiologic data collected during this pandemic,more informatics research is needed to understand how to link viral genetic and epidemiological data anddemonstrate the value of this for disease surveillance. The goal of this supplement is to link epidemiologic data from COVID-19 positive patients in Arizona withviral genetics from sequenced isolates to better understand the relationship between viral genetics andepidemiologic and clinical phenotypes. We will accomplish this by utilizing Arizona's disease surveillancesystem and available sequences and metadata that are published in online nucleic acid databases. We will usedifferent probabilistic matching strategies to link the two different sources (Aim 1) and then use Bayesianphylogenetics and phylogeography to study clustering of epidemiologic cases (Aim 2). Epidemiologists can usethese findings to gain an understanding of how local viruses genetically cluster in relation to specificepidemiologic and clinical cases. While disease severity is dependent on individual immune response andenvironmental factors, linking viral genetics to its proper epidemiologic case could also support hypothesisgeneration for future reverse genetics and immunological studies in animal models.",2020,2021,ARIZONA STATE UNIVERSITY-TEMPE CAMPUS,74688,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility,2020 +C03929,unknown,Impact of Vitamin D on the Chemopreventive Efficacy of Erlotinib against Oral Cancer,"The outbreak of COVID-19 has changed the practice of medicine in a fundamental manner resulting in sweeping changes in healthcare virtually across all medical specialties. Dentistry, in particular, has been dramatically affected by this pandemic, given the close 'person-to-person' contact involved in delivering dental care and treatment procedures that produce aerosols and often result in the dental health care professional (DHCP) contact/exposure to blood, saliva and respiratory droplets. Specifically, the pandemic has led to adaptations to diagnostic and treatment paradigms, modifications to clinical workflow and dental/oral care delivery models. Given that the pandemic is still on-going, the magnitude of the impact of these modified oral health care delivery models, especially in high-risk patient populations (e.g. cancer patients) is not known. This application for a ""Urgent Competitive Revision to Existing NIH Grants (Urgent Supplement)"" is being submitted in response to PA-18-935 to request supplemental funding to the R01DE024595 (PI: Seshadri, Mukund). The research proposed in this supplement was specifically developed in response to the recent coronavirus disease 2019 (COVID-19) pandemic to assess the impact of dental care delivery delays in cancer patients. The proposal is of immediate and high impact to NIDCR.",2020,2021,ROSWELL PARK CANCER INSTITUTE CORP,252300,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2016 +C03930,unknown,Persistence of SARS-CoV-2 in Wastewater,"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), member of the Coronavirus family, hasrecently emerged from Wuhan, China. The World Health Organization (WHO) announced an official name of thedisease [coronavirus disease 2019 (COVID-19)] and classified it as a global pandemic. Though the virus isprimarily spread through person-to-person contact and causes respiratory tract illnesses; some recent studieshave suggested the possibility for fecal-oral transmission and detected the RNA virus in the feces of infectedindividuals, even after respiratory symptoms have subsided. A recent study confirmed that the virus is alsocapable of infecting human gut enterocytes (Lamers et al., 2020). However, the potential transmission of SARS-CoV-2 via wastewater is currently unknown. Therefore, the proposed study here will facilitate a betterunderstanding of persistence and disinfection of SARS-CoV-2 in wastewater. First, we will use laboratory-controlled studies examining the survivability of the virus in wastewater. We will spike the SARS-CoV-2 inwastewater and monitor infectivity over time. Second, we will use chlorine disinfectants to determine theinactivation of SARS-CoV-2 in wastewater. Last, we will conduct a field survey to investigate the fate of the virusin wastewater treatment systems from different locales. The proposed work will provide information to state andfederal regulatory agencies that can be used to develop guidance for prevention of COVID-19. The project willalso aid in evaluation and development of best disinfection approaches and quantitative microbial riskassessment (QMRA). The findings will be invaluable to water resource recovery facilities for better managementagainst potential exposure risk and ensuring worker health and safety.",2020,2021,TULANE UNIVERSITY OF LOUISIANA,416092,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2020 +C03932,unknown,Columbia Partnership for Prevention and Control of HIV/AIDS Clinical Trials Unit,"Project SummaryThe SARS-CoV-2 pandemic has presented the field of infectious diseases and the clinical trials networks witha number of challenges and opportunities. This Administrative Supplement request is being submitted for theparent grant, the Columbia Partnership for Prevention and Control of HIV/AIDS Clinical Trials Unit (ColumbiaPartnership Clinical Trials Unit, grant # 5UM1AI069470). The Columbia Partnership CTU encompasses fourClinical Research Sites (CRSs) and one protocol-specific CRS aligned with three DAIDS-sponsored networks,but this request is focused exclusively to support a crucial activity, the efficient and rapid expansion of SARS-CoV-2 serological and molecular testing in diverse communities served by three of the four CRSs: TheColumbia P&S CRS, Harlem Prevention Center CRS and Bronx Prevention Center CRS. Each of the CRSs, byvirtue of their location in areas highly impacted by COVID-19 disease, relationships with local communities,clinical and scientific expertise of investigators is in a unique position to not only expand testing, but do so byusing innovative strategies and among populations at greatest risk of the disease. The specific aims of thissupplement request are: (1) To leverage the existing clinical, laboratory and administrative infrastructure of theColumbia Partnership CTU to efficiently and rapidly scale-up for SARS-CoV-2 testing activities; specifically tohelp scale up testing in response to the growing need to provide clinical testing to diverse communities heavilyand disproportionately impacted by COVDI-19; and to prepare for upcoming clinical trials investigatingtherapeutic and preventive interventions for COVID-19 disease. (2) To build on the existing communityengagement infrastructure to implement innovative methods to engage local communities and stakeholdersaround SARS-CoV-2 testing and research efforts and to develop a suite of educational materials in support ofCOVID-19 studies.",2020,2020,COLUMBIA UNIVERSITY HEALTH SCIENCES,899977,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Research to inform ethical issues in the Allocation of Resources | Community engagement | Systemic/environmental components of capacity strengthening,2020 +C03933,unknown,An Effectiveness-Implementation Trial of SPIRIT in ESRD,"ABSTRACTThis R01 supplement submitted in response to NOT-OD-20-097, Research on the 2019 Novel Coronavirusand the Behavioral and Social Sciences, addresses one of the four focused areas specified in the notice: toexamine ""downstream health impacts resulting from social, behavioral, and economic impacts, includingdifferences in risks and resiliency based on gender, race and ethnicity, socioeconomic status, and other socialdeterminants of health."" The COVID pandemic has brought fear and uncertainty to all aspects of life andespecially to medical care. Research has shown that after experiencing a natural disaster, people exhibit morerisk averse behaviors, and that belief systems can change: people ""update"" their perception of background riskand perceive the world to be a much riskier place. Although studies have shown that values and preferencesfor end-of-life care are stable over time especially after individuals made an effort to actively think about theirend-of-life preferences, another body of literature suggests that abrupt and disturbing social changes, such asdisasters, can affect the psychological mechanisms underlying cognitive performance. The effects of adisaster may bring doubt to clinicians as well as to families regarding how to interpret an advance directive orend-of-life care preferences that were expressed some time prior to the pandemic. There is very little empiricaldata to guide advance care planning (ACP) with our sickest patients in the setting of a disaster and especiallyone that is so novel. Therefore, we seek to learn whether in the setting of this novel disaster patients withserious chronic illness are more or less likely to want aggressive treatment. This supplement research is togenerate new empirical data on the impact of the COVIDE-19 pandemic on patients' end-of-life preferences, toaddress whether the stability of preferences is disrupted by the pandemic, and to identify patientcharacteristics, including race/ethnicity, associated with pre-/post-pandemic changes. We will leverage theparent study (R01NR017018), a cluster randomized trial of an evidence-based ACP intervention (SPIRIT), inwhich we are currently following 143 dyads (65% Blacks) who successfully completed both the baseline and 2-week post-intervention follow-up before the outbreak. In this new longitudinal cohort study, we will recruit 100dyads from the pool of 143 to repeat the study assessment battery 2 more times along with new COVID-19Stress Scales. The specific aims are to: 1) compare the stability of patients' goals-of-care preferences overtime, from pre-outbreak to during-outbreak, by group (SPIRIT vs control) and estimate effect by race (Blacksand Whites); 2) assess the stability in the preparedness outcomes (dyad congruence, patient decisionalconflict, and surrogate decision-making confidence) comparing pre-outbreak to during-outbreak by group, andestimate race effect; and 3) examine the associations of the COVID-19 Stress, sex, race/ethnicity, and othersociodemographic characteristics (e.g., education level, income) to change in the outcomes and the stability ofpatients' goals-of-care preferences after the COVID-19 outbreak.",2020,2022,EMORY UNIVERSITY,156000,Human Populations,Black | White,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Other secondary impacts,2017 +C03934,unknown,8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA,"The Adolescent Brain Cognitive Development (ABCD) study is the largest long-term study of child health andbrain development in the US, consisting of a Coordinating Center, a Data Analysis and Informatics ResourceCenter, and 21 research sites. The ABCD Study has enrolled a diverse cohort of 11,878 9-10-year-olds andwill continue to track their biological and behavioral development through adolescence into young adulthood.All participants receive neuroimaging, neuropsychological testing, bioassays, and detailed youth and parentassessments of substance use, mental health, physical health, and culture and environment. In March 2020,when our participants were ages 11-13, the world became substantially affected by the COVID-19 pandemic,leading to an upheaval in the economy and the lives of almost every family. Most U.S. schools closed toreduce viral spread. Many parents incurred changes in work (e.g., working-from-home, longer shifts, reducedwages, job loss). Some services and support systems became disrupted. And, the number of confirmed casesand deaths have continued to surge. The massive multifaceted impact of this unprecedented event has thepotential to affect today's children for decades to come. Here, we propose to leverage ABCD's infrastructure,cohort, and existing protocol to rapidly characterize the impacts of the COVID-19 pandemic on each child inthe study. In this proposal, we will capitalize on funded (NSF; PI Tapert) and pending supplements toadminister queries to all ABCD participants and their parents about the impact of the pandemic on their lives(family level impact) by also incorporating publicly and privately available measures of community-levelCOVID-19 impacts. For participants' neighborhoods (e.g., census tract, county, state), we will geocodemeasures of incidence, spatial distancing, changes in (un)employment, and timing of implementation of stateand/or local policies on mitigation practices. By collecting this situational information at the family andcommunity levels as soon as possible, we can use existing ABCD data to examine perturbations indevelopmental trajectories of brain functioning, cognition, substance use, academic achievement, socialfunctioning, and physical and mental health. Specifically, we will (1) focus on characterizing the nature andvariability of the community and regional impact of COVID-19, based on geocoding of ABCD participants'neighborhoods (i.e., current home address) and (2) determine how community-level and family-level impacts ofCOVID-19 differentially influence stress, cognition, and mental health during and after the pandemic. We willanalyze (1) the interactions between family- and community-specific impacts on ABCD participants' immediatestress and mental health during the pandemic, (2) the extent to which such potential impacts are associatedwith each other, and (3) how both community and family factors (e.g., SES, neighborhood characteristics) mayserve as protective factors. This unprecedented crisis provides an opportunity to exploit ABCD's infrastructureand scientific rigor to discern critical dimensions of development not previously envisioned.",2020,2027,Children's Hospital of Los Angeles,180234,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Epidemiological studies",Indirect health impacts | Disease susceptibility,2015 +C03935,unknown,HIV CENTERS FOR UNDEREPRESENTED POPULATIONS IN RESEARCH CTU (HIV CURE CTU) Administrative Supplement,"Project Summary:COVID-19 is a disease caused by SARS CoV-2 virus, a novel coronavirus that has caused apandemic due to lack of immunity to the virus in the general population and lack of effectivetherapy. Increased morbidity due to COVID-19 disease occurs in people age 65 years old andolder, persons with hypertension, diabetes, chronic lung disease, and with immunodeficiency.COVID-19 disease has greatly impacted persons of color in the United States due to a highprevalence of comorbidities in persons of color and due to relative lack of access to medicalcare in persons of color, especially in areas of the country most impacted by poverty and lack ofMedicaid expansion, such as some Southern states in the US, like Texas, which has the one ofthe highest rates of uninsured individuals in the country. Texas currently has had 45,198 casesof COVID-19 with 1,272 fatalities. Harris County/Houston has had 9,050 combined confirmedcases with 199 deaths.The COVID-19 pandemic coincides with the HIV pandemic currently impacting the US and bothSARS CoV-2 and HIV cause high morbidity in Communities of Color. Aside from the impact ofboth viral infections, the socioeconomic and mental health impacts of the public health approachto controlling the spread of COVID-19 disease, social distancing, quarantine, and isolation, havedetrimentally impacted persons with HIV over and above the effects on the general population.Mental health problems, poverty, food insecurity, economic vulnerability, work in serviceindustry where jobs have been eliminated, and lack of safety net for children out of school, alldisproportionately affect persons with HIV.The Texas Children's Hospital (TCH) proposal will address the impact of COVID-19 in childrenand youth living with HIV in the Houston area. TCH will evaluate for prevalent SARS CoV-2infection by performing a PCR evaluation at baseline and in 6 months in 160 children and youthages 2 to 24 years who receive care at TCH. Serology for SARS CoV-2 will also be evaluatedat baseline and in 6 months to look for evolving immunity over time in this population. Surveyswill be administered at baseline and 6 months to evaluate for the socioeconomic and mentalhealth impact of social distancing on these families and youth. COVID-19 disease in personswith HIV infection will be described. Baseline and follow-up demographic, immunologic,socioeconomic, and mental health characteristics of the children and youth enrolled living withHIV will be described.",2020,2020,UNIVERSITY OF CALIFORNIA-SAN DIEGO,300054,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Secondary impacts of disease, response & control measures",Immunity | Disease susceptibility | Indirect health impacts | Economic impacts,2020 +C03936,unknown,Estimating the impact of mammography screening disruptions during the COVID-19 pandemic,"PROJECT SUMMARY/ABSTRACTBreast density is a risk factor for developing breast cancer and decreases the accuracy of screeningmammography. An estimated 27 million women aged 40-74 in the U.S. have dense breasts and theyexperience elevated rates of advanced stage breast cancer diagnoses associated with poor outcomes. Thirty-seven states now require mammography facilities to notify women with dense breasts of the limitations ofmammography and recommend discussion of screening options with their healthcare providers, and a nationallaw is pending. In the absence of screening guidelines for women with dense breasts, there has been adramatic increase in use of supplemental ultrasound screening, which is widely available and has low directmedical costs. Early studies of supplemental ultrasound performance suggest increased cancer detection buthigh rates of false positive exams leading to unnecessary biopsies. The United States Preventive ServicesTask Force has called for studies that evaluate the impact of supplemental ultrasound screening on meaningfulclinical outcomes, such as advanced cancer rates, to inform screening guidelines for women with densebreasts. We recently demonstrated that mammography screening failure rates (i.e., advanced cancers andinterval cancers after a normal mammogram) among women with dense breasts vary widely according toclinical risk factors. Therefore, we propose to assess supplemental ultrasound screening performance within anew risk-based framework. We hypothesize that supplemental ultrasound screening targeted to the subset ofwomen with dense breasts at high risk of mammography screening failures will yield a favorable benefit-to-harm profile. We will use observational data from more than 100,000 screening ultrasound exams and 2 millionmammography screening exams collected via the Breast Cancer Surveillance Consortium to (Aim 1) examinethe test performance of supplemental screening ultrasound according to technique (handheld vs. automated)and type of primary screening (digital mammography vs. digital breast tomosynthesis); and (Aim 2) evaluatesupplemental screening ultrasound outcomes across levels of risk for mammography screening failures. Theseresults will be used as inputs in two simulation models from the Cancer Intervention and Surveillance ModelingNetwork to (Aim 3) evaluate the long-term benefits, harms, and costs of supplemental ultrasound strategiestargeted to women at high risk of mammography screening failures. Our study will be the largest evaluation ofsupplemental ultrasound and the first to evaluate rates of interval and advanced cancers according to risk ofmammography screening failures. Our results will provide urgently needed, actionable evidence for women,healthcare providers, and guideline-makers evaluating screening options for women with dense breasts. Thisevidence will support effective supplemental screening strategies that reduce the burden of breast canceramong women for whom mammography screening is not adequate, while minimizing potential harms.",2020,2025,UNIVERSITY OF VERMONT & ST AGRIC COLLEGE,180000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C03937,unknown,Determining the Impact of Swallowing Impairment in People recovering from Severe COVID-19 Infection,"Project Summary/AbstractThe recent spread of COVID-19 has led to an international pandemic, with >4 million confirmed cases to dateworldwide, of which >1.3 million confirmed cases and >80,000 deaths have been reported in the USA. Infectedindividuals commonly experience severe respiratory difficulties and pneumonia, leading to hospital admissionand the need for intensive care and mechanical ventilation. Emerging evidence suggests that impaired tasteand smell may be early markers of the disease, and that in severe cases, there may be neurological damage inin the medulla, an important brainstem control site for both respiration and swallowing. Given theoverlapping neuroanatomical regulation of breathing and swallowing, we hypothesize that dysphagia(swallowing impairment) will be common in People recovering from Severe COVID-19 (PrSC-19) andassociated with poorer outcomes. Through this grant supplement, we propose to extend our existing workcharacterizing dysphagia profiles in different clinical populations to study dysphagia and its impact in PrSC-19. To understand the prevalence and pathophysiology of dysphagia in PrSC-19, we will conduct detailedanalyses of videofluoroscopies performed during the standard of care, post-discharge from intensive care toregular medical care units within the acute care setting. Given the current limitations in performingswallowing assessments for inpatients who test positive for COVID-19, we will also establish 3 regionalresearch clinics that will offer comprehensive swallowing assessments to PrSC-19 after discharge from acutecare to rehabilitation or the community. These assessments will include the collection of case historyinformation, videofluoroscopy, use of a novel digital stethoscope to measure respiratory-swallowcoordination, measures of other risk factors for dysphagia (e.g. bulbar muscle strength) and patient-reportedoutcomes. Detailed analyses of the videofluoroscopies will identify specific measures of swallowing that falloutside the range of normal variation based on comparison to healthy reference values established throughour research program exploring swallowing physiology on liquids of different consistencies.",2020,2021,UNIVERSITY HEALTH NETWORK,135000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C03938,unknown,COVID-19 effects on children who are deaf or hard of hearing and their families: Rapid and rigorous mixed-methods research to inform care,"PROJECT SUMMARY/ABSTRACTCOVID-19 has unleashed a sudden and sustained disruption to usual healthcare and social milieu in theUnited States, and of particular concern are deaf/hard of hearing (DHH) children who rely on hearinghealthcare and ancillary services for access to auditory language and other supports. Parents of DHH childrenexperience psychosocial pressures even in the best of times, including social isolation, parenting struggles,and stress, all in the broader context of social determinants of health. These challenges have been com-pounded by the spread of COVID-19 which has limited in-person contacts outside the home, including accessto hearing, speech, and language services. A swift response to this public health crisis is essential to informprovision of services to DHH children and their families in the context of ongoing shifts in the social/healthcarelandscape. We will rapidly assess and disseminate timely information about COVID-19's effects on DHH chil-dren and their families. In Aim 1, we will assess DHH child, parent, and family quality of life (QOL), as well ashearing healthcare access and use during the first 10 months of this global pandemic. We will survey parentsof DHH children twice, six months apart, using the recently developed COVID-19 Exposure and Family ImpactSurvey (CEFIS) and other measures. Our analyses will identify characteristics of DHH children and familiesmost negatively impacted by COVID-19. Following each survey wave, we will conduct rapid content analysis ofkey informant interviews with parents reporting better and worse outcomes to obtain deeper insights. In Aim 2,we will assess barriers and facilitators to service provision for DHH children during this public health crisis. Wewill conduct key informant interviews with direct service providers and administrators and use rapid contentanalysis to identify actionable multilevel barriers and facilitators they describe. In Aim 3, we will use a mixed-methods design to integrate our findings at each timepoint, then rapidly disseminate them to stakeholders toinform changes to practice and policy to meet the needs of DHH children and their families. We will use webi-nars, social media, policy briefs, and other modalities most likely to reach a wide array of stakeholders. Im-portantly, our research questions were developed with our Community Advisory Board (CAB), which guidesour ongoing NIDCD-funded R01. The CAB includes parents, direct service providers, and administrators whoare in key positions in state and local agencies and organizations across Kentucky, maximizing the chancesthat our results will influence policies and services responsive to the needs of our target population. This studyis significant because it assesses the effects of COVID-19 on DHH children and their families using a rapid butrigorous approach. It is innovative as one of the first studies to assess the effects of COVID-19 on families withDHH children, a particularly vulnerable and often underrecognized population. Our results will impact the fieldby demonstrating a rapid community-engaged research response to a public health crisis, and by strategicallydisseminating findings in a timely manner to prioritize the needs of DHH children and their families.",2020,2023,UNIVERSITY OF COLORADO DENVER,189453,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Indirect health impacts | Social impacts | Health service delivery,2018 +C03939,unknown,"Expansion of SARS-CoV-2 Testing Supplement, Chicago Clinical Trials Unit","Parent Award Project SummaryThe Chicago Clinical Trials Unit (CCTU) is a consortium of five Clinical Research Sites (CRSs) which willaddress three priority clinical research areas of the NIAID: 1) adult HIV therapeutic strategies including HIVcure, noninfectious comorbidities, and infectious co-morbidities of hepatitis and tuberculosis; 2) vaccines toprevent HIV; and 3) integrated HIV prevention strategies. The CCTU consists of five highly experienced andscientifically productive CRSs that are uniquely positioned to develop, implement and adapt the clinicalresearch priorities of the NIAID clinical research priority areas. The CCTU has a proven track record and willcontinue its productivity through active engagement with a diverse host of at risk and HIV-impactedcommunities, participation in high impact, ground-breaking clinical research studies, efficient management ofresources and critical performance oversight of the clinical activities, laboratories, and pharmacies. The CCTUincludes CRSs and personnel that have long term and productive involvement with three of the researchnetworks; the fourth-antibacterial resistance-being a new network in this consortium. The CRSs and theirnetwork affiliations include: Northwestern University (adult HIV therapeutic strategies); University of IllinoisChicago (vaccines to prevent HIV, integrated HIV prevention), Rush University (adult HIV therapeuticstrategies), University of Chicago (integrated HIV prevention strategies) and Trinity Health & Wellness Center(adult HIV therapeutic strategies). Four of the CRSs are located in Chicago, an ethnically and racially diverseurban area of 9.5 million persons that is the third largest metropolitan region in the United States and one ofthe major urban HIV epicenters. The aims of this proposal are: development, implementation and adaptation ofthe clinical research program of the 1) Adult HIV Therapeutics Strategy Network, 2) the Vaccines to PreventHIV Network, 3) the Integrated HIV Prevention Strategies Network, and 4) Bidirectional engagement of therelevant and at risk HIV-infected/impacted communities with the CCTU clinical researchers. The CCTU is wellpositioned to reach diverse populations and contribute significantly to the NIAID research agenda.",2020,2020,NORTHWESTERN UNIVERSITY AT CHICAGO,814136,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,,,,United States of America,,,,2020 +C03940,unknown,Alpha7 Nicotinic Receptor: Structures and Coupling with Intracellular Proteins,"The alpha7 nicotinic acetylcholine receptor (α7nAChR) has emerged as a unique player in the infection andprogression of COVID-19, which has caused more than 325,000 deaths. α7nAChR links tobacco smoking tomajor clinical manifestations in COVID-19, including respiratory infection, anosmia, systemic coagulopathy, andcytokine storm. Several sequences of SARS-CoV-2 are found to be homologous to α-bungarotoxin and α-cobratoxin, potent antagonists of α7nAChR. These findings support the hypothesis that SARS-CoV-2 interactsdirectly with α7nAChR, inhibits its function, and consequently dysregulates the inflammatory responses mediatedby α7nAChR. The experimental evidence is urgently needed to correctly establish the role of α7nAChR inCOVID-19 and to understand nicotine's detrimental or protective effects on the onset and progression of COVID-19. With permission from the NIDA (Dr. Roger Little, Deputy Director, Division of Neuroscience and Behavior),we seek Administrative Supplement support to address several key questions about the involvement of nicotineand α7nAChR in COVID-19. Specifically, we propose to elucidate: (1) where and how SARS-CoV-2 proteinsinteract with α7nAChR and how nicotine alters such interactions; and (2) how SARS-CoV-2 proteins affectintracellular signaling pathways downstream of α7nAChR that lead to upregulation and transactivation of pro-inflammatory cytokines, and how nicotine modulates the outcome of this process. Considering the widespreadexpression of α7nAChR in various organs and the significant regulatory role of α7nAChR in the cholinergic anti-inflammatory pathway, our research outcomes can potentially lead to new treatment strategies to combatCOVID-19.",2020,2023,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,156491,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2018 +C03941,unknown,Development of Broad-Spectrum Antiviral Therapeutics by Destabilizing the Main Protease of Coronaviruses,"AbstractAt the moment, there is a worldwide outbreak of coronavirus disease 2019 (COVID-19) that is caused by theinfection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We urgently need effectiveanti-viral therapeutics against SARS-CoV-2 and related coronaviruses to avoid potential future outbreaks. Thisproposal seeks pilot funding to support the interdisciplinary collaboration between medicinal chemists andvirologists to develop novel small molecules that can destabilize 3-chymotrypsin like protease (3CLpro), themain viral protease that is essential for the replication of SARS-CoV-2 and many related coronaviruses. Theproposed small molecules are able to catalyze the degradation of 3CLpro through the host cell's ubiquitin-proteasome-system, which routinely removes damaged or unfolded proteins.The proposed degraders are bifunctional molecules with a short linker between two ligands. One ligand bindswith high selectivity to an E3 ubiquitin ligase while the other ligand simultaneously engages the viral proteintarget. As the binding event occurs, the viral protein is brought in close contact with the E3 ubiquitin ligasecomplex and is poly-ubiquitinated for degradation in the proteasome. The degrader is then released tocontinue its catalytic activity for the degradation of the viral protein. The degrader only needs to bind transientlyto the target viral protein to induce its ubiquitination, which offers many advantages over traditional smallmolecule inhibitors.We selected 3CLpro as the primary target for selective degradation based on its key role in viral replication andthe availability of selective inhibitors, which will serve as the ligand that binds to 3CLPro. Although inhibitors for3CLpro exist, degraders' catalytic properties will render them much more potent. By destabilizing anddestroying the viral protein instead of stoichiometrically binding to the viral protein, degraders should also actfaster than inhibitors. 3CLpro is conserved among many coronaviruses including SARS-CoV, MERS-CoV, andSARS-CoV-2. The proposed small molecule degraders can be potent antiviral therapeutics against a broadspectrum of coronaviruses, including viral strains that are resistant to antiviral inhibitors. In aim 1, we willprepare bifunctional small molecule degraders by linking ligands of E3 ligase and 3CLPro using our recentlydeveloped two-stage strategy. In aim 2, we will evaluate the degradation and anti-viral activities of 3CLProdegraders in cell-based assays.The research groups of PI and Co-Investigator are highly experienced in bifunctional small molecule degraderdevelopment and anti-viral research, respectively. The proposed study will produce important proof-of-conceptdata for the development of novel antiviral therapeutics against SARS-CoV-2 and related coronaviruses.",2020,2022,UNIVERSITY OF WISCONSIN-MADISON,427052,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C03942,unknown,Philadelphia HIV Therapeutics and Prevention Clinical Trials Unit,"ABSTRACTThe pandemic of COVID 19 has had and will continue to have a profound impact in the research operations ofthe Philadelphia CTU and its associated CRSs (Therapeutic and Prevention)The Aim of this supplemental request is to facilitate the return of safe and efficient clinical Research operationsat the Philadelphia CTU, critically affected by the COVID 19 epidemic.We anticipate the following needs for our CTU from now until December 1st, 2020: 1. Personnel. We anticipate needs of at least one Clinical Research Coordinator in both the Therapeutic and the Prevention CRS. This need is necessitated to maintain the clinical staff required to implement COVID-19 related clinical activities while regular HIV-related trials resume; and in order to minimize risks to workers among our current staff who are at higher risk for severe illness from COVID-19 who will require limited time ""in office"" and face-to-face exposure to clinical trial participants. 2. Clinical supplies to ensure the safety of our employees and the clinical trial participants (Personal protective equipment, masks, gloves, face shields etc.). We are also anticipating that our institution will increase the requirement for COVID-19 testing of our personnel and our clinical trials participants. 3. Increased personnel in the laboratory to allow it to remain operational in the case that one of our employees needs to be quarantined or falls sick in the following months. 4. Equipment and testing kits for the clinical laboratory at the hospital of the University of Pennsylvania to ensure that the increased testing needs associated with our clinical research operations do not tax the regular clinical operations of the laboratory.",2020,2020,UNIVERSITY OF PENNSYLVANIA,299668,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,,,,United States of America,,,,2020 +C03943,unknown,A Microfluidic System Coupling Amplified Nanofluidic Virion Purification and Mass Spectrometry for Detection of SARS-CoV-2,"A Microfluidic System Coupling Amplified Nanofluidic Virion Purification and Mass Spectrometry forDetection of SARS-CoV-2There is an urgent need for new methods and alternative techniques for viral detection in response to the SARS-CoV-2 pandemic. A novel strategy is proposed for viral detection that purifies the virions with ananofluidic/microfluidic (NF/MF) system prior to protein analysis by mass spectrometry. The NF/MF purificationsystem and protein analysis are highly complementary to and a radical departure from existing approaches. TheNF/MF system addresses the fundamental challenge of rapid and efficient purification of virions from the hugebackground of human cells and biomolecules. This novel approach will enable mining of the rich information thatis contained in the protein structures of the virus. In contrast with most other approaches, this technology will becapable of detecting mutated strains of SARS-CoV-2 and emergent viruses.The performance of the novel NF/MF will be fully characterized for different clinical needs. First, the extractionefficiency of the NF/MF system and the limits of detection for the complete diagnostic system will be measured.Second, application specific data acquisition and analysis strategies will be developed for the MS that are tunedto: 1) achieve the best detection limits for diagnostic testing, and 2) to gain the greatest percentage of the viralproteome for enhanced diagnostics for patients with high-viral loads.In addition to the gains in capabilities, it is expected that performance, costs, and sample throughput will befavorable. It is anticipated that limits of detection of 10 virions or better will be achieved with sample throughputof a few thousand samples per day per system. The simplicity of the process and ease of automation will reducepersonnel costs. Only a few consumables will be used that are orthogonal to the supply chain for RNA basedmethods. Thus, this technique is highly complementary to RNA-based approaches and would reducevulnerability to supply chain disruption. It is anticipated that these figures of merit and the potential applicationsfor utilizing the structural information contained in the proteins has the potential to revolutionize viral diagnosticsin both short-term and long-term.",2020,2021,UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN,334234,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2018 +C03945,unknown,Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes,"SUMMARYThe SARS-CoV-2 pandemic demands a swift response to address a broad range of medical and scientificquestions to mitigate harm to populations and slow and eventually eliminate the epidemic. To understand thecourse, history, and pathogenesis that will lead to effective therapies and vaccines it is critical to answerseveral fundamental scientific questions longitudinally: Viral, genetic, ecological factors and co-morbidity/co-infections risk factors need to be identified for 1) symptomatic and asymptomatic infection; 2) prolongedshedding; and 3) acute and chronic sequelae. In particular we must define correlates of reduced viral loadin upper airways early in disease, and the host-viral response that defines later severe lowerrespiratory disease and ARDS that is prefaced by cytokine storm. We hypothesize that a combination ofviral (high viral load, specific viral signature of virulence, respiratory viral co-infection and virome), ecological(such as, microbiome community structure/function) and host (local mucosal immune response) factors willpredict disease outcomes and severity. Below are our specific aims to address our hypothesis: Aim 1:Determine longitudinal kinetics of SARS-CoV2 viral load to establish association between nasal viral load andviral shedding with disease severity. Aim 2: Characterize how SARS-CoV2 infection changes nasalmicrobiome composition, structure and secondary bacterial infection during Covid-19. Aim 3: To examine ifnasal microbiome patterns during SARS-CoV2 infection are associated with local immune responses andcytokine storm. Collectively, this study will identify determinants of SARS-CoV2 viral kinetics, persistence,virus-host and microbiome interactions. Specifically, our proposal will advance our understanding of the role ofthe upper airway microbiome in Covid-19 and establish its role in programming of the local immune responseupon SARS-CoV2 infection and effects on Covid-19 outcomes.",2020,2021,Vanderbilt University Medical Center,303897,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03946,unknown,Systems Approach to Immunity and Inflammation,"This proposal represents a highly innovative and perhaps unique approach to lay the foundation forunderstanding the pathogenesis of COVID19-driven pathologies in man. Here we bring three distinct scientificapproaches together in a novel and coordinated fashion to analyze key steps in innate immune response toCOVID-19 infection. The fundamental studies of the NLRP3 inflammasome pathway is both deep and broadgiven the nearly 20-year experience of the Ulevitch lab in studying various members of the NLR family at thelevel of pathway analysis. While drawing on information from studies in murine cells (genetic, biochemical andcell biologic) the focus here is on human Mϕ where the Ulevitch lab has built a broad approach withimmunologic, cell biologic and genetic approaches. The Nolan lab has pioneered the use of high contentimaging approaches for analyzing cells and tissues. The high parameter technologies maximize the breadth ofimmune features analyzed in samples for rapid discovery. CyTOF gives 42-channel info for millions of cells inblood. CODEX spatially resolves single cells in tissues with >60 parameters, while ViralMIBI brings viralnucleic acid detection to antibody-based multiparameter imaging defining cellular niches of infection.Combining these technologies with SARS-CoV2 challenge models and the Collaborative Cross will also resultin the identification of mouse models that most closely match the disease phenotypes and molecularsignatures of COVID-19 disease in humans. If deemed useful we can also use information and/or murinestrains derived from forward genetic efforts in the Beutler lab. The latter has been an integral part of theScripps U19 program since the initial funding in 2001/2002.",2020,2022,SCRIPPS RESEARCH INSTITUTE,366597,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C03947,unknown,Generating Novel Humanized Mouse Models for in vivo COVID19 Mechanism Studies and Therapeutics Tests,"PROJECT SUMMARY The COVID19 pandemic has spread across the globe with unprecedented speed anddevastation. With infected individuals rising past 1.4 million in the US, there is a dizzyingamount of information causing confusion around which tissues SARS-CoV-2 infects and how ittriggers catastrophic immune response and tissue destruction. Furthermore, with the rapidlyincreasing number of candidate therapies, there is an urgent need for animal models thatfaithfully recapitulate the human disease and is scalable to provide power for preclinical testing. We will use our extensive expertise in mouse genetics to generate two novel mouse modelsthat express human viral receptor ACE2 (hACE2) in either selected cell types/tissues of interestor in the endogenous pattern of ACE2 expression in mice. Expression of the hACE2 gene willallow efficient SARS-CoV-2 infection. We will use infected humanized mice to dissect theprogression of COVID19 from initial infection of host cells, to antiviral and pro-inflammatoryresponses, to development of acute respiratory distress syndrome, using single cell approachessuch as single cell RNAseq. In parallel, we will also use infected humanized mice to test theeffectiveness of candidate FDA approved drugs for their effectiveness in halting COVID19. Weexpect that these humanized mouse models will be valuable platforms for a large number ofCOVID research directions listed as Areas of High Priority in PAR-20-177.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN DIEGO,434000,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C03948,unknown,SUPPLEMENT - Systems Analysis of Social Pathways of Epidemics to Reduce Health Disparities,"SummaryThis application is in response to the urgent need to understand the epidemiological and economicimpact of SARS-CoV-2 in the US. Due to the diverse and complex factors driving this outbreak,understanding the epidemiological and economic impact requires a detailed model of individual andcommunity level activities and mobility, for which it is essential to have a high resolution agentbased model (ABM), rather than metapopulation models. This research will build a detailed, age-strati ed, ABM of SARS-CoV-2 which takes into account the heterogeneity in demographics andsocial interactions among individuals. A large number of novel data sources will be integratedto calibrate the model and to infer the parameters. Due to unobservable parameters such asthe asymptomatic rate, and constantly changing behaviors and compliance to social distancing,the calibration, simulation and analysis of such an ABM is very challenging, and require highperformance computing resources. The calibrated model will be used to simulate di erent kinds of counterfactual scenarios thatwould include di erent types of social distancing strategies { school closure, home-isolation, quar-antine of symptomatic and diagnosed cases, liberal leave policy, and low ecacy vaccines andantivirals. Sensitivity analysis on compliance and duration of social distancing, transmissibility,epidemic severity, and ecacies will be performed. Novel interventions such as \pulsing' of theeconomy i.e. odd/even day closure or alternative week closure will be simulated. The workforcedisruptions due to illness, deaths and prophylactic absenteeism will be used to measure indus-try level inoperability and its cascading e ect on other industries and on the US Gross NationalProduct. Various epidemic and economic outcome metrics will be compared across scenarios andtrade-o s between outcomes will be measured and explained. Epidemic outcomes will be measuredin terms of morbidity, mortality, time to peak and peak infections whereas economic outcomes willbe measured in terms of cost of illness, and cost of prevention due to social distancing directives.Multiple rankings of the scenarios will be provided based on mortality, cost of illness and overallmacroeconomic impact.",2020,2023,UNIVERSITY OF VIRGINIA,381948,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Economic impacts,2014 +C03949,unknown,Experimentally Guided Modeling and Simulation for Cholera Dynamics,"Project Summary/AbstractThe pandemic of the Coronavirus Disease 2019 (COVID-19) is currently on-going with massive numbersof cases and high morbidity and mortality. The disease is caused by a novel coronavirus which is nownamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Effective control strategies forCOVID-19 rely on a deep understanding of the transmission dynamics of SARS-CoV-2. Meanwhile,policy making in the management of the pandemic is significantly impacted by the interaction betweenthe outbreak development and the economic growth, and there is currently a paucity of researchexamining such interaction. The overall objective of this proposal is to establish a new mathematical andcomputational modeling framework to investigate the transmission and spread of SARS-CoV-2 in the USbased on available data, and to analyze the impact of the COVID-19 pandemic on public health and theeconomy. To achieve this objective, the team will pursue two specific aims: (1) Modeling the spread andhealth impact of COVID-19; (2) Modeling the economic impact of COVID-19. The proposed research issignificant because it is expected to advance the current understanding of COVID-19 transmissiondynamics, to provide realistic prediction on the development and long-term evolution of the diseaseoutbreak, and to quantify the interaction between epidemiological and economic factors under the impactof COVID-19, all of which are important for the control and management of the pandemic. The approachis innovative in the development of a sophisticated mathematical and computational framework thatincorporates both the epidemic and economic aspects of COVID-19, and in the integration of rigorousmathematical modeling and analysis, intensive numerical simulation, and realistic epidemic data. Theproject represents an interdisciplinary collaboration among an applied and computational mathematicianwith long-term interest in infectious disease modeling (Wang), an epidemiologist and health scientist withextensive working experiences at CDC (Heath), a business and management professor with abackground in public heath (Mullen), and a data analyst and geographic information system expert (Mix).The success of this project will not only build a solid knowledge base for the complex transmissiondynamics of COVID-19, but also provide important guidelines for the government and the public healthadministration in pandemic management and policy development.",2020,2022,UNIVERSITY OF TENNESSEE CHATTANOOGA,105618,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Economic impacts,2019 +C03950,unknown,Role of Pellino-1 in COVID-19 diseases,"SUPPLEMENT PROJECT SUMMARY Severe acute respiratory coronavirus 2 (SARS-CoV-2, also named as Coronavirus disease 2019 virus(COVID-19)) initially emerged in China in late 2019 and has rapidly spread to more than 70 countries in earlyMarch, 2020 with over 80,000 confirmed human cases world-wide. The World Health Organization hasdeclared COVID-19 disease as a Public Health Emergency of International Concern. Neither effective vaccinesnor treatments are available. A recent study of COVID-19 patients reported a close correlation of high levels ofcirculating inflammatory cytokines with the severity of illness in patients infected with the virus. This suggeststhe virus-induced cytokine storm may serve as a therapeutic target of COVID-19 diseases. Pellino-1 (Peli1),an ubiquitin ligase mediates inflammatory cytokine responses in multiple cell types, including lung epithelialcells and central nervous system resident cells. We have previously demonstrated that Peli1 induces microgliaactivation and promotes lethal encephalitis during West Nile virus infection. Peli1 also mediates inflammatorycytokine responses in bronchial epithelial cells and alveolar macrophages during influenza virus and rhinovirusinfection. Neutralization of Peli1 attenuates virus-induced airway inflammation. The goal of the parent grant isto understand the role of Peli1 in mediating inflammatory cytokine responses in Zika virus - infected humanneural stem cells and induction of congenital zika syndrome in animal models. In this supplement project, incollaboration with Dr. Vineet Menachery, an expert in coronavirus biology, we will investigate the role of Peli1in COVID-19 disease. Specifically, we hypothesize that Peli1 mediates inflammatory cytokine responses inairway epithelial cells upon SARS-CoV-2 infection and blocking Peli1 signaling reduces airway inflammationand attenuates COVID-19 disease in mice. In Aim 1, we will determine the role of Peli1 following in vitro SARS-CoV-2 infection in human lung epithelial cells. In Aim 2, we will determine the therapeutic effects of Smaducin6in animal models of SARS-CoV-2 infection. Initially, we will characterize SARS-CoV-2 infection in aged BALB/cmice. Subsequently, we will determine if treatment with Peli1 inhibitor attenuates COVID-19 disease in mice.Results from this study will provide important insights into CoVID-19 pathogenesis. In addition, identifying themediators responsible for alterations in lung inflammation is key to prevention and treatment of CoVID-19diseases.",2020,2021,The University of Texas Medical Branch at Galveston,184865,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2019 +C03951,unknown,Designing neutralization antibodies against Sars-Cov-2,"Project SummaryCOVID-19 has become a worldwide pandemic whose rapid spread and mortality rate threatens millions of livesand the global economic system. Developing effective treatment such as neutralization antibodies is an urgentneed. We propose here to develop a new method to design antibodies strongly bind to the SARS-CoV-2receptor binding domain (RBD) that is necessary for viral entrance to human cells. We will develop a novelapproach that combines directed evolution, deep sequencing and interpretable neural network models toefficiently identify strong and specific antibodies. This method will allow analyzing large sequencing data setsof antibody variants against the SARS-CoV-2 RBD in order to derive superior binders that do not exist in theoriginal library. Iteration through directed evolution and computational design will efficiently identifyneutralization antibody candidates that can be used as potent therapeutics to treat COVID-19.",2020,2022,UNIVERSITY OF CALIFORNIA-SAN DIEGO,433750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03952,unknown,Overriding the Immune Evasion Tactics of Coronavirus,"PROJECT SUMMARY/ABSTRACTProgression of SARS-Coronavirus-2 (SARS-CoV-2) infected patients to life threatening disease may result froma virus-mediated, dysregulated immune response associated with excessive production of inflammatorycytokines, cytokine release syndrome. In this proposal we seek to identify therapeutics and knowledge ofCoronaviruses that will counteract the disruption in cytokine signaling pathways involved in effective hostdefense. We contribute to the urgent need for therapeutics that inhibit SARS-CoV-2 infection using pathwayspecific reporter cells to screen for therapeutically active compounds that restore cytokine signaling. Our pathwayspecific screens are a component in SBP-wide initiative to develop therapeutics that limit severe COVID-19. Ourscreening strategy selects drugs identified in libraries of pharmacologically active therapeutics that block SARS-CoV-2 lytic replication. We use cytokine pathway reporters to test these compounds in SARS-CoV-2 infection ofa lung cell line and human lung organoids in BSL3 facilities. The selected candidates will undergo analysis forpotential drug development. Fundamental knowledge of cytokine-regulated defense mechanisms related to Coronavirus infectionlimits the rational design of therapeutics and vaccines. To advance this knowledge we focus on the Lymphotoxin-β Receptor (LTβR) and the Herpesvirus entry mediator (HVEM, TNFRSF14) pathways known to regulate anti-viral cytokines, interferons (IFN) and interleukin-1(IL1β). Together, the LTβR and HVEM pathways act as anintegrated, homeostatic network that inhibits virus replication yet limits tissue damaging cytokines. Two SARS-CoV-2 proteins, the Papain-like protease (PLPro, Nsp3) and Nsp9 target novel components in the TRAF3interactome that control the NFκB transcriptome. We will determine the role of these components in the keycytokine pathways using genetic and pharmacologic approaches in a mouse coronavirus lung infection model.Together these two independent but complementary aims will provide an opportunity to help solve the SARS-CoV-2 pandemic, and protect future generations.",2020,2025,SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE,617996,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C03953,unknown,The effects of exposure to violence on risk for substance abuse: neural mechanisms and community level moderators,"Project SummaryIt is well known that stressful events, such as those occurring as a result of COVID-19 prevention efforts, are apotent trigger for the initiation and escalation of illicit substance use. However, it is not well known how stresstriggers increased substance use, which could help improve understanding, prevention, and treatment ofsubstance use disorders. Therefore, our ongoing longitudinal study of adolescents was designed to test thehypothesis that stress during development recalibrates the neural processes underlying threat and rewardreactivity as well as working memory capacity, which leads to increased risk for the initiation and escalation ofsubstance use. Because COVID-19 related social distancing is a profound stressor, measuring it's effectsprovides an opportunity to better understand these hypothesized pathways by which stress increasessubstance use. Therefore, we propose to recontact adolescents (n=309) and caregivers (n=246) in ourongoing longitudinal study to assess changes in stress, cognitive function, and substance use due to theCOVID-19 pandemic at two time points. At both time points, youths will also complete a working memorycapacity task and delay discounting assessment and have their locations tracked with GPS for a week whilethey receive 35 ecological momentary assessment (EMA) prompts to assess their momentary stress, socialinteractions, substance use, and feelings at particular locations as was done in prior waves. In Aim 1, we focuson 3 particular categories of stress to understand their relative contribution to increased substance use: (1)Social distancing experiences: the GPS and questionnaire assessments of activity patterns provide aquantitative, state-of-the-art measure of the magnitude of change in individual mobility elicited by COVID-19social distancing; (2) Economic hardship: Because our sample is socioeconomically diverse (37.4% haveannual household incomes under $30,000), we will have the opportunity to clarify the effects of increasedeconomic challenges on substance use; (3) Social isolation and conflict: The questionnaire and EMA data onfrequency of interpersonal interaction and conflict provide the opportunity to determine if these are also triggersof increased substance use. In Aim 2, potential cognitive mediators of these effects will be assessed using themeasurement of working memory capacity and delay discounting. These youths have already completed aneuroimaging session that assessed neural structure (anatomy and connectivity), resting state activity, andactivity during tasks probing working memory capacity (Emotional N-Back), reward reactivity (viewing imagesof marijuana, e-cigs, and alcohol), reward anticipation (Monetary Incentive Delay), and threat reactivity(emotional faces). Because these same procedures will be repeated as soon as research activity can resumeafter COVID-19 restrictions are lifted, Aim 3 will be to determine how COVID-19 related stress moderateschanges in neural structure and function as well as the degree to which these neural changes predict changesin substance use.",2020,2022,OHIO STATE UNIVERSITY,154959,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2017 +C03954,unknown,A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups,"PROJECT SUMMARY/ABSTRACTFor COVID-19, persons who inject drugs (PWID) have been identified as a population at high-risk of exposureto SARS-CoV-2 (the virus that causes COVID-19) because of their increased risk of homelessness orincarceration-situations linked to increased rates of the disease transmission and co-infection with HIV-1.Given that a SARS-CoV-2 vaccine is likely 12-24 months away, there is a critical unmet medical need for medicalcountermeasures that could contain COVID-19 outbreaks in the general population and in these difficult-to-reachhigh-risk populations such as PWIDs in particular. Moreover, there is a fundamental gap in our understandingof SARS-CoV-2 infection and pathogenesis in these at-risk PWID populations. Evidence indicates that SARS-CoV-2 infects and depletes T lymphocytes and many HIV-infected PWID have limited access to antiretroviraltherapy and consequently exhibit pre-existing CD4+ T-cell depletion. Hence, SARS-CoV-2 infection couldaccelerate clinical progression to AIDS, or alternatively, SARS-CoV-2 infection in HIV+ PWID could exacerbateCOVID-19 clinical symptoms leading to elevated risk of death. Thus, HIV+ PWID may be at elevated risk ofdeath from SARS-CoV-2 infection. In these PWID populations, reducing T-cell depletion would be highlybeneficial to halting clinical progression and may a viable long-term therapeutic goal. The specific objective ofthis supplement proposal is to repurpose existing technologies to rapidly develop a Gene Drive Therapy (GDT)candidate for SARS-CoV-2 and quantify its breadth of interference and transmission in vitro in patient T-cellsfrom HIV+ PWID. This effort will build heavily off our recent success in engineering an HIV-1 GDT (see ParentAward) and a GDT against Zika Virus (ZIKV), demonstrating that the GDT concept can be repurposed for otherviruses. The central hypothesis-based on extensive preliminary studies in HIV and ZIKV-is that a putativeSARS-CoV-2 GDT, depleted of all the pathogenic viral genes, could target the same cells as wild-type SARSCoV-2 (including T lymphocytes), compete for intracellular resources, and reduce SARS CoV-2 viral load andpathogenesis, thereby serving as a single-administration therapeutic. The rationale for a GDT countermeasurefor SARS CoV-2 is based on extensive data for HIV-1 in humanized mice and positive FDA meetings. We willachieve our objectives via two specific aims: (i) Engineer a SARS-CoV-2 GDT candidate (by adapting the existingBioreactor platform); and (ii) Test the SARS CoV-2 GDT candidate's protective effect on patient T-cells from anHIV+ PWID cohort in Tijuana Mexico. While the GDT approach carries inherent risks, single-administrationtherapeutics would be highly beneficial particularly for treating difficult-to-reach, high-risk PWID populations.Regardless of the success of GDTs in protecting against T-cell depletion, the studies proposed here will havebroad fundamental significance by assaying how SARS-CoV-2 infection impacts T lymphocytes from HIV+PWID. These studies would also provide validation of a novel medical countermeasure with the potential to berapidly deployed against new viral threats.",2020,2025,J. DAVID GLADSTONE INSTITUTES,189000,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03955,unknown,Deep phenotyping in Electronic Health Records for Genomic Medicine,"SUMMARYSharable, innovative and scalable methods for abstracting relevant characteristic patient phenotypes fromelectronic health records (EHRs) and for systematically understanding disease relationships are critical foraccomplishing precise disease diagnoses and personalized disease prevention and treatment for patients.As of May 28, 2020, there are 5,716,271 confirmed 2019 Novel Coronavirus (COVID-19) cases worldwide,including 1,699,933 cases in the United States, and 356,124 deaths across over 200 countries, areas, andterritories including 100,442 deaths in the United States, with the numbers continually climbing. The pandemichas had profound economic, social, and public health impact. As Columbia University Irving Medical Center(CUIMC) has been fighting the virus on the frontline in the epicenter of New York City and treating more than4,100 SARS-CoV-2 positive patients, we aim to address the urgent COVID-19 Public Heath need bydeveloping sharable phenotyping methods to identify and characterize COVID-19 cases using our EHR dataand multiple data standards, including the Observational Medical Outcomes Partnership (OMOP) CommonData Model (CDM) and the Human Phenotype Ontology (HPO), and generate novel knowledge about COVID-19, such as its risk factors, disease subtypes, and temporal clinical courses.Our specific aims for this supplement are as follows: Extension to the original Aim 1: Develop and validatescalable and sharable approaches to abstracting characteristic phenotypes of COVID-19 from both structuredand unstructured EHR data and to standardize the concept representations of these EHR phenotypes usingwidely adopted data standards, including the OMOP CDM, HPO, SNOMED-CT, UMLS, and RxNorm.Extension to the original Aim 3: Develop and validate methods for temporal phenotyping for COVID-19 andmethods for identifying disease subtypes of varying clinical outcomes among heterogeneous populations usingdeep characteristic EHR phenotypes of COVID-19.We will disseminate the resulting methods and knowledge with the broad scientific communities and the nation.We will also leverage this supplement to create research and training opportunities for postdocs and graduatestudents from biomedical informatics, data science and computer science, advancing interdisciplinarycollaborations in data science and biomedical informatics to combat COVID-19 and other health problems.",2020,2021,COLUMBIA UNIVERSITY HEALTH SCIENCES,74999,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C03956,unknown,Structural and functional analysis of the coronavirus spike protein fusion peptide,"Project Summary / AbstractEnveloped viruses access their host cells by binding to receptors on the plasma membrane and then undergoingfusion with the host membrane. Both binding and fusion are mediated by a specific viral ""spike"" protein that istypically primed for fusion activation by proteolytic cleavage to expose the fusion peptide. Coronavirus fusionspike protein (CoV S) is a complex biomolecular machine that has a novel fusion peptide with has a great dealof inherent flexibility in its fusion reaction. This is exploited by these viruses in their diverse entry pathways andis a primary determinant of viral tropism. We have pioneered the concept that that the proteolytic cleavage eventsin S that lead to membrane fusion occur both at the interface of the receptor binding (S1) and fusion (S2) domains(called S1/S2), as well as adjacent to a structurally and functionally novel fusion peptide within S2 (called S2').Thus, there are notable differences between CoV S and most other class I fusion proteins including: 1) that theproteolytic events liberating the fusion peptide are diverse, and 2) that the fusion peptide itself is atypical insequence compared to other fusion peptides, containing a mixture of important hydrophobic and negatively-charged residues, and may represent a larger than normal fusion ""platform"" instead of a defined ""peptide"". Thusfusion peptide activity is likely controlled by reorganization of the fusion platform, based on both hydrophobic(i.e. lipid-binding) and ionic (i.e. Ca2+) interactions. Despite the recent availability of S structures in their pre-fusion state, there remains a very limited mechanistic understanding of membrane fusion for the CoV family, orany structural information to correlate structural biology aspects of S to its function in membrane fusion. Thisinformation is critical to understanding viral pathogenesis and CoV emergence into the human population. Wepropose an integrated biophysical, biochemical, and in vivo approach to study the unique cleavage-activatedregulation of CoV S protein, using Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acuterespiratory syndrome coronavirus (SARS-CoV) as primary models. We will use state-of-the-art spectroscopyand an innovative single particle tracking technique to study S protein fusion peptide function, and combine thesewith in vivo infectivity studies, including at BSL3, will allow a complete picture of CoV fusion activation. Theseapproaches will reveal how structure and function vary depending on the key activators of S; i.e. receptor binding,protease availability and the local ionic environment. These studies will allow us to determine common principalsthat can be applied to all CoVs, moving the field forward with these innovative studies will provide criticalknowledge about CoV entry and tropism needed to safeguard human health from an emerging pathogen likelyto cause severe outbreaks, and for which few or no medical countermeasures exist.",2020,2022,CORNELL UNIVERSITY,229985,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C03957,unknown,Augmenting Cognitive Training in Older Adults: COVID Admin Supplement,"ABSTRACT:This randomized clinical trial will test whether transcranial direct current stimulation (tDCS) of frontal cortices enhancesneurocognitive and functional outcomes achieved from cognitive training in older adults experiencing age-relatedcognitive decline. Change in well-validated measures of neurocognitive function and everyday abilities will serve asoutcome measures. Functional and structural neuroimaging biomarkers of neural plasticity and learning (fMRI, GABAMRS, etc.) will measure intervention-associated alterations in specific brain regions impacted by cognitive aging. tDCSis a noninvasive brain stimulation method that facilitates neural plasticity and learning. Accordingly, when used as anadjunctive intervention, tDCS may augment cognitive training effects. This study will leverage existing multisite clinicaltrial infrastructure at McKnight Brain Institutes located in two of the states with the largest representation of older adultsin the United States: University of Florida, University of Miami, and University of Arizona. Adults over the age of 65represent the fastest growing group in the US population. As such, age-related cognitive decline represents a majorconcern for public health. Recent research suggests that cognitive training in older adults can improve cognitiveperformance, with effects lasting up to 10 years. However, effects are typically limited to the tasks trained, with littletransfer to other cognitive abilities or everyday skills. Effects may also be reduced in people with Alzheimer'sdisease risk factors. A two-phase multisite randomized clinical trial will examine the individual and combined impactof pairing cognitive training with transcranial direct current stimulation (tDCS) in older adults experiencing age-relatedcognitive decline (n = 360; 120 per site). Participants will consist of elderly men and women 65-90 years of age withevidence of age-related cognitive decline, but not MCI or Alzheimer's disease (MoCA≥25). We will compare changesin cognitive and brain function resulting from CT and CT combined with tDCS using a comprehensive neurocognitive,clinical, and multimodal neuroimaging assessment of brain structure, function, and metabolic state. Functionalmagnetic resonance imaging (fMRI) will be used to assess brain response during working memory, attention, andmemory encoding; the active cognitive abilities trained by CT. Proton magnetic resonance spectroscopy (MRS) willassess markers of neural plasticity, GABA concentrations, and cerebral metabolism. We hypothesize that: 1) tDCSwill enhance neurocognitive function, brain function, and functional outcomes from CT; 2) Effects of tDCS on CT willbe maintained up to 12 months following training, and 3) Neuroimaging biomarkers of cerebral metabolism, neuralplasticity (GABA concentrations) and functional brain response (fMRI) during resting vs. active cognitive tasks willpredict individual response to tDCS, with certain Alzheimer's risk factors (e.g., APOE4 genotype, family history ofAlzheimer's disease) predicting poorer cognitive and functional outcome. To date, no studies havecomprehensively examined combined CT and tDCS intervention in the elderly. This study will provide definitive insightinto the value of combating cognitive decline in a rapidly aging US population using tDCS with cognitive training.",2020,2021,UNIVERSITY OF FLORIDA,717683,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2016 +C03958,unknown,Mechanistic elucidation of inflammasome assembly and regulation. Supplement: Testing drugs that curtail inflammasome activation to suppress SARS-CoV-2 pathogenesis,"AbstractInflammasomes are supramolecular signaling complexes that activate a subset of caspasesknown as inflammatory caspases such as caspase-1. Upon stimulation by microbial anddamage-associated signals, inflammasomes assemble to elicit the first line of host defense byproteolytic maturation of cytokines IL-1b and IL-18, and by induction of pyroptotic cell death.Assembly of an inflammasome requires activation of an upstream sensor, a downstreameffector, and in most cases an adaptor molecule such as apoptosis-associate speck-like proteincontaining a caspase recruitment domain (ASC). Depending on whether ASC is required,inflammasomes can be categorized into ASC-dependent and ASC-independentinflammasomes. Despite the biological importance of inflammasomes in innate immunity, nostructural and mechanistic information is available.This proposal seeks to link SARS-CoV-2 infection to inflammasomes and to test whetherinflammasome inhibitors alleviate SARS-CoV-2 pathogenesis. Inflammasome activation, inparticular through the NLRP3 inflammasome and the pore forming protein GSDMD, underliesthe serious, and often fatal cytokine storm, lung inflammation and sepsis that are associatedwith SARS-CoV-2 clinical deterioration. It may even contribute to lymphopenia, an importantcharacteristic of severe COVID-19 cases. These data from SARS-CoV-2 and from relatedcoronaviruses, SARS-CoV and MERS-CoV, led us to propose the following hypothesis: thesevere acute respiratory syndrome (SARS) pneumonia induced by SARS-CoV-2 is caused bymassive inflammatory cell infiltration and elevated proinflammatory cytokine/chemokineresponses that depend on GSDMD and/or NLRP3 activation.",2020,2021,BOSTON CHILDREN'S HOSPITAL,264999,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C03959,unknown,Intestinal allograft tolerance in large animals,"Project Summary: There is growing evidence that an overexuberant innate and adaptive immune responsemay contribute to life-threatening pulmonary pathology in COVID-19 disease. On the other hand, inadequateviral control may allow severe disease to develop. Human immune system (HIS) mouse models have enormousand unique potential to model human COVID-19. Unlike other animal models, HIS mice could be used tounderstand the role of the innate and adaptive human immune systems in both controlling and driving SARS-CoV2-mediated disease and hence be used to optimize therapeutic approaches. The goal of our proposal is tooptimize HIS mouse models for these purposes. Specifically, we propose to: 1) Optimize our HIS mousemodels for the study of COVID-19. Existing mouse models are limited by the lack of human ACE2, the SARS-CoV2 receptor, in the respiratory tract. We will implant iPS cell-derived human lung bud organoids generatedfrom cord blood HSC donor cells into HLA-A2 Tg NSG mice receiving HLA-A2+ cord blood HSCs. In a secondapproach to humanizing mice for COVID-19 mouse studies, we will use CRISPR/Cas9 to replace the murineACE2 gene with hACE2, allowing physiologic expression of hACE2 in NSG mice. Human HSC recipients will betreated with mouse TSLP in an AAV vector to enhance murine thymic and lymph node structure and therebyimprove human T cell development and improve peripheral vaccination responses. An alternative approach toenhancing thymus function will involve grafting of multiple pieces of thymocyte-depleted neonatal human thymustissue in multiple sites to compensate for the lack of growth potential (compared to fetal thymus) of neonatalthymus tissue. Immune reconstitution, T cell reconstitution and lymphoid structure will be followed and humoraland cellular responses to live attenuated SARS-CoV2 virus vaccination will be measured; 2) Use optimized HISmouse models to determine the kinetics of disease pathogenesis and the role of human immunecomponents in controlling infection and mediating pathologic host responses. We will first employ HISmice constructed with human cord blood HSCs and autologous iPSC-derived lung bud implants and later utilizethe above HLA-A2 hACE2 Tg model. Baseline infection with SARS-CoV2 will be assessed in non-reconstitutedanimals and compared to HIS mice. In HIS mice, we will deplete various human immune components (T cells,B cells or macrophages) to determine their impact on the course of infection and pathology associated withSARS-CoV2. In hACE2 Tg mice we will investigate the kinetics of infection of various components of therespiratory tract in combination with analysis of the human immune cell infiltrates in each locale over time. Withthese models established, we will be positioned to test therapeutic approaches during different phasesof SARS-CoV2 infection in future studies. Collectively, our models will provide critical information on the roleof human immune components in driving and protecting from COVID-19-associated pathology, allowingaccelerated optimization of immunomodulatory therapies.",2020,2022,COLUMBIA UNIVERSITY HEALTH SCIENCES,283116,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2020 +C03960,unknown,"Maternal Marijuana Use During Pregnancy, Marijuana Legalization, and Adverse Obstetrical and Neonatal Outcomes: A 12-year Cohort Study","PROJECT SUMMARY/ABSTRACTThe COVID-19 pandemic has high potential to lead to broad increases in substance use among pregnantwomen (e.g., via increased social isolation and loneliness due to extensive ""shelter-in-place"" orders,psychological and financial distress, fear of infection). Further, smoking, vaping and other substance use mayincrease risk for COVID-19 and its more serious complications; pregnant women are an ideal population tostudy the effects of substance use on COVID-19 risk and illness progression as they have reduced immunefunctioning and, in Kaiser Permanente Northern California (KPNC), are routinely screened for substance useas part of standard prenatal care. The proposed study represents an unparalleled opportunity to efficientlyleverage rich, valid and contemporary prenatal substance use data by self-report and urine toxicology testingfrom our existing R01 study (DA047405) in innovative ways. For Aim 1, we take advantage of a unique naturalexperiment using interrupted time series analyses to examine whether the COVID-19 pandemic is associatedwith broad increases in prenatal substance use overall and among vulnerable subsets of pregnant women(e.g., those with prenatal depression, low socioeconomic status (SES)) using data from ~200,000 pregnanciesuniversally screened for prenatal substance from January 2018 to December 2021. For Aim 2, we will conducta retrospective and prospective longitudinal cohort study of ~100,000 pregnant women from January 2020 toDecember 2021, to examine whether substance use in the year before pregnancy, and during pregnancy, isassociated with increased risk of COVID-19 onset and severity of illness. COVID-19 data will be ascertainedfrom KPNC's innovative tracking and surveillance system which includes laboratory confirmed COVID-19infection, persons under investigation with symptoms who have not yet been tested, symptom severity, medicalcomplications, and mortality. These data will be efficiently linked to prenatal substance use data ascertainedfor the parent grant using the electronic health record with high generalizability and a large sample size. Ourresults will provide sorely needed and generalizable data on the impact of this pandemic on rates of prenatalsubstance use and the impact of substance use on COVID-19 onset and progression. Results will guidepreventive measures, public health interventions, and health services, and can inform best practices to protectpregnant women against potential long-term health consequences of this pandemic.",2020,2024,KAISER FOUNDATION RESEARCH INSTITUTE,162108,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2019 +C03961,unknown,SARS-CoV-2 and Influenza Infection in the Syrian Hamster,"PROJECT SUMMARYIn a few months, a potential second wave of CoVID-19 will be superimposed on theinfluenza season, which starts in the fall and typically peaks between December andFebruary in the United States. By then, the majority of Americans are unlikely to beimmune to SARS-CoV-2. An effective SARS-CoV-2 vaccine is likely to take months toyears to achieve widespread protection. In addition, reduced social distancing is likely toelicit regional surges in CoVID-19. Potential synergy between these two respiratorypathogens could result in significant morbidity in the short-term. In the long term, we facethe reality that SARS-CoV-2 may assume endemic status and may interact with otherseasonal respiratory pathogens for the foreseeable future. The overall goal of thisproposal is to determine whether prior influenza infection worsens CoVID-19- likedisease in the SARS-CoV-2 Syrian hamster model. Recent studies indicate that ACE2may be upregulated by influenza infection. The Syrian hamster supports infection withhuman influenza A H1N1 subtypes as well as contemporary H3N2 subtypes that cannotreplicate in mice. Additionally, the Syrian hamster is a faithful spontaneous animal modelof CoVID-19. We will pursue two aims: 1) to characterize interferon-driven immuneresponses and ACE2 expression in hamsters infected intranasally with contemporaryH3N2 and H1N1 influenza strains and 2) to characterize clinical disease course, immuneresponses and translationally relevant biomarker alterations following SARS-CoV-2infection of acutely infected and recovered influenza-infected hamsters. We will use afactorial design to assess the effects of controllable variables (influenza virus infectionalone, combined influenza/ SARS-CoV-2, acute/recovered status and sex) on clinicallyrelevant outcome measures (body weight, duration/severity of clinical illness andpulmonary injury scoring). Cytokine, immune and ACE2 responses will allow us toassess association of these variables with infection status and clinical phenotype. Theseapproaches will provide direct and translationally relevant data regarding impact ofinfluenza on SARS-CoV-2 clinical phenotype, as well as advance understanding ofunderlying immune responses.",2020,2022,YALE UNIVERSITY,450500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,H1 | H3,H1N1,,H3N2,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C03962,unknown,Efficient Statistical Learning Methods for Personalized Medicine Using Large Scale Biomedical Data,"Project Summary: Coronavirus disease 19 (COVID-19) has created a major public health crisis around the world. The novelcoronavirus was observed to have a long incubation period and extremely infectious during this period. No proveneffective treatment or vaccine is available. Massive public interventions have been implemented in many countriesand states in the United States (US) at different phases of the outbreak with varying combinations of social dis-tancing, mobility restriction and population behavioral change. Decisions on how to implement these interventions(e.g., when to impose and relax mitigation measures) rely on important statistics of COVID epidemiology (e.g.,effective reproduction number) that characterize and predict the course of COVID-19 outbreak. However, there isa lack of robust and parsimonious model of COVID epidemic that can accurately reflect the heterogeneity betweensusceptible populations and regions (e.g., demographics, healthcare capacity, social and economic determinants).There is no rigorous study to guide precision public health interventions that are tailored to a population or regiondepending on their characteristics. Furthermore, due to the non-randomized nature of public health interventions,it is critical to account for biases and confounding when comparing mitigation measures of COVID-19 across re-gions. To address these challenges, this project develops robust and generalizable analytic methods to evaluatepublic health interventions and assess individual patient risks of COVID-19 infection and complications. In Aim 1,we will develop dynamic and robust statistical models to predict the disease epidemic. The models will estimatethe date of the first unknown infection case, instantaneous effective reproduction number, and account for the incu-bation period of COVID-19 virus. Furthermore, heterogeneity in population's demographics, social and economicindicators, healthcare capacity and geographic locations will be incorporated to reflect their impacts on COVIDepidemic. Under a longitudinal quasi-experimental design, we will provide valid inference for comparing publichealth interventions implemented at different regions while accounting for confounding bias. Multiple sources ofdata from different states in the US will be analyzed to empirically test which states' response strategies are moreeffective and in which subpopulation. In Aim 2, we will focus on developing precise risk assessment tool of individ-ual COVID-19 patients using electronic health records (EHRs) collected at New York Presbyterian hospital in NewYork City, an epicenter of COVID-19. We will engineer features of patient's pre-conditions associated with severeCOVID complications, recovery, or death. More importantly, we will engineer features that represent proxies of virusexposures from patients' geographic information. We will use machine learning techniques to create quantitativesummaries of patient prognosis (e.g., transitioning to serious clinical stages, discharge, death). We will use inter-nal cross-validation and external calibration to validate developed algorithms. The project will generate evidenceto guide precision public health intervention, optimal patient care, and efficient healthcare resource allocation inanticipation of a second wave of COVID epidemic and in preparation of other infectious disease outbreaks.",2020,2022,University of North Carolina at Chapel Hill,331147,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2018 +C03963,unknown,"COVID-19 Knowledge and Attitudes among Nursing Home Patients, Family and Staff.","COVID19 has especially impacted residents in skilled nursing facilities and long term care(SNF/LTC). Who are at extraordinary risk for infection and mortality. Residents with dementiaare at even higher risk because of their need for individual personal care, lack of cognition, andthe impact of social distancing and reduced social interaction on their underlying dementia. Thestaff and family members at SNF/LTCs are facing major challenges in confronting a newinfectious disease, imposing visitation and socialization limits, and needing to identify newworkflows to provide care to this group of residents who often have significant physical andmental health impairmentThis Supplement builds on our previous R21 work in SNF/LTCs and partners with 2 BaltimoreSNF/LTCF network. We will use two complementary models to inform formative research and todevelop a survey instrument which will ultimately guide an intervention: (1) Knowledge,Attitudes and Behavior (KAB) which is individual-focused; and, (2) Systems EngineeringInitiative for Patient Safety (SEIPS), a Human Factors and Systems Engineering model, whichdefines the interactions among humans and other elements in complex sociotechnical worksystems. Integrating both models will identify both knowledge gaps for the educationalintervention and facilitators and barriers within the work system that may require structuralmodification. This is an NIA-defined Stage 0 Behavioral Intervention. The formative researchphase of Aim 1 will include in-depth qualitative research with resident, family, and staffstakeholders in SNF/LTCFs. This will include 25 in-depth interviews with residents and/or theirfamily members, 15 interviews with facility staff. The interview domains will address both KABand human factors issues including intervention facilitators and barriers. This will informdevelopment of a survey instrument in Aim 2, which combines the KAB and SEIPs approachesand which will be piloted in 50 residents/family and 20 staff members, to include post-hocfeasibility assessments. Data obtained from the formative research and pilot surveys willsupport the ultimate objective of developing an interactive intervention in Aim 3 based onbehavioral science and human factors engineering principles, which will inform facility workflowredesign and a potential clinical trial intervention.",2020,2021,JOHNS HOPKINS UNIVERSITY,163750,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions,2019 +C03965,unknown,Development and significance of the plasma cell niche in the human infant thymus,"SUMMARYWhile children can contract SARS-cov-2, they usually develop a milder form of the disease than adults. Acommon explanation is that their immune system is more robust than that of adults. Based on our previousresearch on B cell immunity in human neonates, we hypothesize that innate humoral immunity present at birth,and dwindling with age, confer a first line of defense against SARS-CoV-2, attenuating the severity of thedisease. Our studies will test for the presence of natural IgM, IgG and IgA reactive to major components of thevirus (spike, nucleocapsid...) in neonates and adults. Moreover, we have already generated >300 recombinantmonoclonal antibodies (mabs) from plasma cells isolated from neonatal thymus specimens. We will test theantiviral activity of these mabs. If successful, our studies will uncover a critical immune component responsiblefor children's apparent resistance to SARS-cov-2. We will also identify specific mabs with therapeutic potential.Aim 1. To assess natural serological immunity to SARS-CoV-2Studies in aim 1 will test for the presence of IgM, IgG and IgA reactive to SARS-cov-2 proteins in the serum ofneonates and healthy adults as controls. Experimentally, we will use plasma and serum samples collected beforethe start of the COVID-19 pandemic. Our repository already includes 48 cord blood specimens and 35 healthyadult blood specimens as controls. As a source of antigens, we will first use commercially available recombinantviral proteins. We will also test the reactivity of cord blood antibodies to viral proteins expressed in primary humanairway epithelial cells.Aim 2. To identify recombinant monoclonal antibodies with therapeutic potentialAs part of our ongoing study on the development of humoral immunity in human neonates (U01-AI-131339), wehave generated 362 recombinant monoclonal antibodies (mabs) from plasma cells isolated from 5 neonatalthymus specimens. These mabs are a representative sample of the natural antibody repertoire of neonates.Experiments in aim 2 will assess the reactivity of these mabs to SARS-CoV-2 antigens. All reactive mabs will befurther characterized for their reactivity profile, sequence and capacity to neutralize SARS-CoV-2 infectivity.",2020,2022,COLUMBIA UNIVERSITY HEALTH SCIENCES,394144,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C04105,EP/V028456/1,GCRF_NF39: COVID-19 Child Abuse Prevention Emergency Response,"The COVID-19 Parenting project will reach 57 million families in DAC countries during the COVID epidemic, with evidence-based resources to prevent violence against children and reduce parenting stress. DAC countries are facing far-reaching COVID epidemics, with cyclical periods of lockdowns and school closures (Mahler, 2020). Parents and caregivers globally are caring for children under exceptionally stressful conditions. Even the most secure families are struggling to manage children within extended lockdowns. Shouting and physical violence are worsened by stress, poverty, alcohol use, confined and crowded conditions (Meinck, 2017), all heightened under COVID-19. UNICEF reports global escalation in child abuse, with severe health, social and economic impacts. We will work with the World Health Organisation, UNICEF, the Global Partnership to End Violence, UNODC, USAID, the US Centers for Disease Control and other NGOs including the Special Olympics, World Without Orphans and local DAC country community organisations to: 1. Adapt parenting programs with demonstrated effectiveness into scalable resources for DAC countries, using the best evidence. This will include text message-based systems and low-data ir or offline app support for families. 2. Deliver parenting support programs and resources to 57 million families in an initial 14 DAC countries, through partnerships with UN agencies, NGOs and faith-based organisations. Translate resources into relevant DAC country languages to facilitate uptake. 3. Evaluate mechanisms of delivery, costs and their impact on reduction in violence, parenting and stress through online pre-post repeated surveys and in-depth qualitative research with families in DAC settings. We will achieve a rare outcome for research translation: direct delivery of support to 57 million families in DAC countries. It is exceptional value for money, with a cost to UKRI of less than one penny (£0.008) per DAC family receiving evidence-based violence prevention support during COVID-19.",2021,2021,University of Oxford,623432.04,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,Digital Health,,,South Africa,South Africa,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C04106,EP/V028200/1,GCRF_NF46 Children's learning and development in the time of Covid19: Evidence from an ongoing longitudinal study in Ghana,"The COVID-19 pandemic and related social and economic crises are undermining children's education in low- and middle-income countries through school closures, unequal access to remote-learning activities, and increased household food insecurity and poverty. Groups at greater risk, including girls and children from the poorest families, are likely being disproportionately affected, amplifying existing inequalities in child education, health and broader development. We embed in an ongoing longitudinal project, Quality Preschool for Ghana, a study of the pandemic's repercussions on children's education and broader development for a representative sample of urban Ghanaian boys and girls aged 10-12 years (N=~2,000), their households, and teachers (N=~400). We have four main goals. First, we investigate household and child vulnerability and resilience to the crisis, with three phone surveys with parents and one phone survey with children starting in late summer, followed by already-funded child and parent direct assessments later in the 2020-2021 school-year. Second, with three additional phone surveys with teachers, we generate new data on how children, parents and teachers are faring with the remote-learning implemented during school closures and with re-entry into in-person schooling should that happen in the 2020-21 school year. Third, by piggy-backing on already-funded data collection activities planned for later in the Fall 2020 and Spring 2021, and combined with four prior rounds of data on these children starting in preschool, we examine inequalities in the effects of the crisis on learning and broader child development domains (health, psycho-social outcomes). Fourth, we monitor changes in poverty and food security and examine their associations with later-in-life children's educational outcomes. The proposed study provides the Ghanaian government with unique, real-time data to inform remote-learning, school-reentry, how children, families and teachers are coping with the crisis, and social-protection efforts. Results will provide timely and much-needed academic and policy insights for Ghana and broader global educational efforts to protect children from the long-term effects of the pandemic on their learning and development.",2021,2021,Imperial College London,104969.04,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Ghana,Ghana,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C04107,EP/V028332/1,GCRF_NF55 Fast-track vaccine cold-chain assessment and design for mass scale COVID-19 vaccination in Bangladesh (VaCoBD),"Universal vaccine access is an existing major challenge in low-income countries, mainly due to the lack of robust cold-chains, resulting in loss of potency for +25% of vaccines. Mass vaccination for COVID-19 globally will require a new fast-track approach to assess, re-engineer and build upon available cold-chain logistics assets and systems, to deliver the vaccines at scale and speed never before considered. We aim to evaluate the capacity and preparedness of the cold-chain framework of Bangladesh as a case study country for mass scale COVID-19 vaccination, and assist the policymakers in defining optimised, sustainable interventions and lasting legacy opportunities. Our objectives are: (1) evaluating the context and resilience of cold-chains and resources in Bangladesh, collecting primary data for a robust assessment of the cold chain capacity and gaps; (2) developing a bottom-up whole systems approach building upon existing logistics infrastructure, and distribution systems for mass scale COVID-19 vaccination including modal shifts; (3) developing a cost-benefit analysis framework for the bottom-up (vaccine) systems model; (4) assessing different intervention scenarios for mass-scale COVID-19 vaccination preparedness, and helping shape the country's immunisation strategies and priorities; (5) informing policymakers and other key stakeholders, including Monetary Financial Institutions about the cost-effective intervention alternatives for cold-chain development for mass-scale vaccination for COVID-19, which may be useful for future emergency or disasters; and (6) disseminating learnings to other countries, including methodology, to assess their requirements and to simulate best options for creating sustainable temperature-controlled supply-chains for health and medical supplies in epidemics and natural disasters.",2021,2022,University of Birmingham,620898.96,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,South-East Asia,,,,United Kingdom,Bangladesh,"Vaccines research, development and implementation | Health Systems Research | Research on Capacity Strengthening","Medicines, vaccines & other technologies | Cross-cutting",2020 +C04108,EP/V028499/1,GCRF_NF98_Building an Early Warning System for community-wide infectious disease spread: SARS-CoV-2 tracking in Africa via environment fingerprinting,"Mitigating the rapid global spread of Covid-19 requires real-time data on community infection prevalence in order to guide targeted intervention measures on regional, national and global scales. Individual diagnostic testing is of paramount importance for short- and long-term management of the pandemic, but limits on capacity (both of kits and trained workers) mean that healthcare settings are prioritised over the community. Here we propose a novel supplemental low-resource approach for broad community-wide surveillance of SARS-CoV-2 infection prevalence. We aim for a real-time Covid-19 risk prediction platform for community-wide diagnostics via wastewater-based epidemiology (Figure 1). Disease markers present in domestic wastewater can reveal the health status of contributing population, and we propose that this includes the infection prevalence by SARS-CoV-2. Real-time spatiotemporal estimation of this novel coronavirus in urban water across several sites in South Africa (Cape Town) and Nigeria (Lagos) will provide a broad picture of community infection prevalence, even for asymptomatic cases, as well as the level of acquired immunity, thus identifying hotspots for priority testing, contact-tracing and quarantine and will provide more accurate projections of the spread of the virus and the infection fatality rate. As communities contribute directly to wastewater, we will be able to estimate true infection rate at the community level, including also asymptomatic and pre-symptomatic people. The virus loading levels will be used to establish status and time trends. This would enable rapid identification of hot spots for management via targeted intervention measures and potentially support important decisions regarding entry into and exit from 'lockdown' periods as well as focussed screening of selected communities.",2021,2022,University of Bath,422561.04,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,South Africa | Nigeria,Epidemiological studies,Disease transmission dynamics,2020 +C04109,EP/V028162/1,GCRF_NF94: Identifying and mitigating the impacts of COVID-19 on legal and sustainable wildlife trade in LMICs,"To contain COVID-19, there has been a clampdown on wildlife trade, which is a key source of livelihood and food security for hundreds of millions of people in LMICs. Wildlife markets have been closed, new bans on wildlife trade are being enforced and governments are proposing drastic changes to wildlife trade regulations. These reforms aim to safeguard global public health and global food systems, yet they disrupt wildlife supply chains that meet peoples' food security and economic needs. The clampdown on global wildlife trade also risks pushing trade underground with implications for public health, conservation and crime. The aim of this project is to develop evidence-based guidelines for regulating wildlife trade to address the risks of COVID-19 without undermining legal and sustainable wildlife trade economies. This project will use trade data, interviews and the Delphi method to: (1) track changing wildlife trade trends during the pandemic; (2) assess the impacts of these changing trends on people engaged in wildlife economies; and (3) formulate new guidelines for safe, legal and sustainable wildlife trade in the COVID-19 era. The project will be informed by evidence from Kenya and Cameroon - two LMICs with wildlife sectors that stand to be significantly impacted by COVID-19. This project will be led by an international, interdisciplinary team of wildlife trade, conservation and livelihood experts, and implemented in collaboration with CIFOR, an institute at the forefront of research on wildlife trade in LMICs. An Expert Impact Network (IUCN, IIED, TRAFFIC) has been established to realise impact.",2021,2022,University of Birmingham,323792.04,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Kenya | Cameroon,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Other secondary impacts | Health leadership and governance,2020 +C04110,EP/V028197/1,To develop a Zambian context specific short and long term model for managing COVID-19 pandemic and future infectious disease outbreaks.,"Pandemics such as COVID-19 bring significant challenges for all health services, especially those in low-middle income countries. This trauma, emergency and critical care nursing project was developed with our established partners in Zambia, Ministry of Health, Nursing and Midwifery Council, Lusaka College of Nursing and Ndola College of Nursing, in recognition that the COVID-19 pandemic will have a short, medium and long-term impact on healthcare delivery and workforce. While funding streams may focus on the current COVID-19 pandemic itself, the likelihood of future outbreaks of COVID-19, new or known infectious diseases, cannot be discounted. Therefore, solutions must be sought to address the effects of diverting resources from an already over stretched workforce with limited resources. In Zambia, nurses are the only professional group who are present at every stage of the patient pathway, from initial contact in a rural health clinic or emergency and trauma services through inpatient services to discharge and rehabilitation. Individually they have more patient contact than all other professional groups combined. These nurses need to have increased capacity in leadership, management and clinical decision-making. These attributes, essential to prevent healthcare systems becoming overwhelmed enable nurses to identify and respond appropriately to the rapidly changing health needs that arise during outbreaks of infectious diseases and pandemics. They include the ability to develop and implement strategies for containing infected cohorts and preventing the disease spreading. Our shared needs assessment early in the pandemic. identified the urgent need to up-skill their healthcare workers for what is likely to be rapidly increasing need. These will enable them to be both proactive and reactive in their responses to the COVID-19 pandemic and other infectious diseases. This project will be conducted in three phases. Phase 1: Communities engagement examines how the 73 tribes, with their own language, cultural beliefs and traditions engage with the limited community healthcare services. The nurses live alongside and with the communities they serve, and have a very wide remit, being expected to treat whoever seeks their assistance. This includes communicable and non-communicable diseases (for all age groups), public health and prevention. Consequently, the COVID-19, with its rapid onset and high, unprecedented incidence inevitably impacts adversely on services that the community relies on. Phase 2: Documentary Data Analysis will be used to analyse, interpret and national documentation, health statistics and information, to complete a gap analysis regarding COVID-19. Much of the information, guidance, education and training that the MoH have been able to access was developed in High-Income Countries, and may not be apposite for the Zambian context. Therefore, this project will identify strategies that can build on (and not adversely impact on), current Zambian health systems and structures. Phase 3: Development of processes for practice and enhanced nursing response to COVID-19, combining results from phases one and two to develop educational and clinical processes and procedures for practice; and make recommendations for policy for dealing with COVID-19. This includes planning for a possible second wave, and future infectious disease outbreaks. Deliverables from this research include recommendations for national and international policy makers. A national curriculum and competency assessment document for Bachelor of Science in Trauma and Emergency Nursing and critical care specialist practice. The sharing of outputs via webinars and virtual conference/actual conferences, and peer-reviewed journal papers. It will facilitate knowledge exchange and transfer between healthcare professionals Zambia and UK and support the establishment of an international community of practitioners with expertise in COVID-19 management.",2021,2022,Birmingham City University,201051.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Zambia,Zambia,Health Systems Research,Health workforce,2020 +C04111,EP/V028014/1,"GCRF_NF119 Poverty, vulnerability and crime: What does COVID-19 mean for Nigerian street vendors?","Since the novel coronavirus hit countries and communities around the world, the global response has included strict lockdown and social distancing measures. The Nigerian Federal Government (FG) has largely copied these measures and imposed an indefinite ban on street vending across the country. But how sustainable are these measures given their devastating effects on millions of Nigerian street vendors? Is a total ban on street vending the right approach? How are street vendors coping? Are they prepared to engage in crime, and if so, what types of criminal activity? What immediate actions can government take to support street vendors during and beyond COVID-19? Bringing together an ambitious team of UK- and Nigeria-based researchers, working in partnership with the Nigerian Federal Ministry of Justice, our project seeks to provide urgent solutions to these critical questions. Street vending is the foremost manifestation of Nigeria's informal economy, accounting for over 70% of the country's urban employment. The vendors offer a wide range of goods and services for sale in public spaces and earn a living either through daily monetary transactions or the exchange of services through bartering. Many battle poor hygiene, diseases, economic hardship, drug abuse, prostitution, physical and sexual abuse - all of which have worsened since the onset of COVID-19. Despite recent FG's move to ease lockdown and social distancing restrictions, the continued ban on street vending in fact threatens the lives and livelihoods of these informal workers. Responding to the UKRI GCRF/Newton Fund call, our project will provide new insights on the most pressing socioeconomic difficulties facing the poorest and most vulnerable people in Nigeria. We will focus on how COVID-19 lockdown and social distancing measures have worsened the socioeconomic plights of Nigerian street vendors (e.g., loss of income and hunger), their coping strategies, as well as their susceptibility to crime (e.g., burglary, prostitution and illegal drugs trade). We will also explore street vendors' perspective on what government and policymakers can do to assist them urgently. Using a qualitative research approach, our 18-month project will achieve lasting impact on government policy through in-depth interviews on street vendors' experiences and reactions to COVID-19 lockdown, and also three workshop events aimed at creating new co-produced evidence alongside government representatives, policymakers and street vendors themselves. Findings from our project will provide actionable knowledge to help improve the FG's understanding of, and response to, the COVID-19 outbreak and wider concerns around job creation, crime prevention and social protection for the poor and most vulnerable in society.",2021,2022,University of Sussex,219988.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C04112,EP/V028464/1,GCRF_NF109: GCRFCV19@ukri.org African elections during the COVID-19 pandemic,"Elections involve increased risks of the spread of COVID-19, with the International Foundation for Electoral Systems (IFES) highlighting more than 40 stages where people assemble, or objects are transferred during the electoral cycle. Despite these risks, a number of elections have already taken place in Africa during the pandemic, including those in Mali, Guinea, and Burundi. Nine more elections are due to take place in Africa before the end of 2020, and there are 18 scheduled for 2021. Reducing the risks of increased transmission during these elections is paramount, particularly as the World Health Organisation (WHO) has recently declared that the pandemic is accelerating on the continent. By following three elections (in Tanzania, Ghana and the Central African Republic) from beginning to end, we will look closely at each stage of the electoral process and how the risks of COVID-19 transmission have been mitigated (if at all). We will also chart the extent to which holding elections has had a demonstrable effect on infection rates. Secondly, we aim to assess whether and how the pandemic affects political participation. We will evaluate whether the ability of any social (including gendered) groups or geographic populations to engage in the political process is reduced, either unintentionally or deliberately. These public health and governance foci will allow us to produce detailed, evidence-based, and context-specific recommendations that can be applied to upcoming African elections. The findings will also be valuable to all other low- and middle-income countries (LMICs) that are due to hold elections.",2021,2021,University of Edinburgh,453645.72,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,Gender,,,United Kingdom,Central African Republic | Ghana | Tanzania,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Other secondary impacts,2020 +C04113,EP/V028146/1,"GCRF_NF72 Development, evaluation and implementation of a digital support to improve the management of cancer and mitagate the impact of COVID-19","Over half a million people in Vietnam currently live with cancer or provide care to a relative or friend with the disease. Support and care in the form of palliative care or supportive units are rare in Vietnam. As a result, 70% of patients die at home, in the care of their families. Many families affected by cancer manage severe health issues with minimal knowledge and little help from health care professionals. Providing this care can have a significant negative impact on the carer's health and their ability to work. These challenges have worsened due to COVID-19 as many hospitals appointments throughout Vietnam were cancelled or treatments postponed. As a consequence of these disruptions, many families are managing cancer in isolation. Prior to 'lockdown', we conducted workshops with 100 patients, carers and health care professionals across five regions of Vietnam. Patients and families reported that they require urgent assistance to understand cancer, manage medications, daily personal care needs, nutrition, wound care, emotional issues, how to tell if a patient's health is getting worse and when you should seek help. In response to these needs, we hosted a workshop in March 2020 with cancer experts from across Vietnam to design a remote digital cancer management tool to provide families the support, information and skills they require. This project aims to develop this digital resource called V-CCC (Vietnam -Cancer Caring Coping) to support families to manage cancer remotely. The team have developed a written version of the digital support V-CCC. This project will 1) Develop the digital version of V-CCC 2) Evaluate the impact V-CCC may have on patient and carer outcomes 3) Explore V-CCC usage throughout the country. We will develop the best possible digital advice and information by working together as a large group of doctors, nurses, carers, patients, academics and allied health professionals from across all regions of Vietnam. An expert digital supports team will transfer this information online ensuring that it is easy to use e.g. videos/pictures/ interactive games. We will demonstrate the V-CCC in workshops involving 50 carers from five different regions of Vietnam (Hanoi, HCMC, Hue, Danang and Can Tho). Changes will be made to V-CCC based on this feedback. We will then evaluate the V-CCC with 150 carers (and patients if willing) across five cancer hospitals (Hanoi, Ho Chi Mhin City, Can Tho, Danang and Hue). Nurses in cancer hospitals will recruit participants and assist them to complete baseline measures (mental health, quality of life, health literacy). Cancer carers will be provided with a web-link and access code to V-CCC for two weeks. Participants will be asked to complete follow-up surveys identical to those they completed at the onset. We will then conduct 30 online interviews over Skype with a range of carers to explore their experiences of using V-CCC. We will also ask N=15 Health Care professionals to share their thoughts and experiences of V-CCC interviews. Following evaluation, partners will widely distribute V-CCC throughout Vietnam using hospital clinics, waiting rooms, advocacy groups and social media. We will use google analytics to explore how many people access the resource, from which region and how long they use the resource for. We hope that V-CCC will reduce isolation, poor management and ultimately deterioration of cancer outcomes that have increased due to COVID-19. The lessons we learn during this project will be exchanged with our academic partners in Colombia , Uganda and Malaysia so that they too can learn how remote digital management tools may be useful in those countries.",2021,2022,Queen's University of Belfast,249767.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Caregivers | Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Western Pacific,Digital Health,,,United Kingdom,Viet Nam,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04114,EP/V028103/1,GCRF_NF101: Internally Displaced Persons and COVID-19: Leveraging local low cost COVID-19 solutions in informal settlements in Zimbabwe,"This project focuses on Internally Displaced Persons (IDPs) residing in informal settlements in Harare, Zimbabwe. Zimbabwe is among the latest countries in the region to be affected by the COVID-19 pandemic. Whilst the government has responded well to the pandemic, it is currently preoccupied with returning citizens, some of whom are testing positive on arrival, leading to increasing numbers in infection cases. The system is neglecting the plight of secluded populations such as IDPs, most of whom are of a migrant/refugee heritage and were victims of developmental displacement programmes (e.g. the infamous land reform programme) who lack resources and access to critical public health information. Bringing together an interdisciplinary team of two UK universities, three Zimbabwe universities and a local NGO, this impact-oriented project aims to complement the government's current response to the pandemic by adapting locally developed low cost COVID-19 solutions to fit IDPs' needs. Objectives are to: 1. identify through research what IDPs know about COVID-19, sources of the knowledge and current preventive/protective measures and the gaps; 2. adapt the recent low cost COVID-19 innovations (e.g. sanitisers and facemasks) developed by our co-investigator university, Zimbabwe Ezekiel Guti University, to fit the IDPs context; 3. develop a COVID-19 transformative public health education programme to be accessed through diverse interactive communication channels; 4. produce a toolkit and provide training through media to empower women to make COVID-19 protective products for use by their households; 5. produce policy briefs for engaging relevant government departments to include IDPs in their development plans.",2021,2022,University of Nottingham,275272.8,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Zimbabwe,Zimbabwe,"Infection prevention and control | Policies for public health, disease control & community resilience","Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Communication",2020 +C04115,EP/V028480/1,"GCRF_NF106 Entrepreneurial resilience & recovery during and after covid-19 crisis: firm- & community-level responses in Wuhan, Malaysia, and Thailand","Moscarini and Postel-Viney (American Economic Review, 2012) showed that entrepreneurs are central for economic resilience during an economic crisis and for kickstarting recovery as the crisis attenuates. However, we know little about how this potential can be best harnessed during a covid-19 -style economic emergency, which not only causes a sharp demand shock, but also, requires businesses to radically reconfigure their operations to comply with social distancing. This knowledge gap is particularly acute for low- and middle-income economies, as most studies of entrepreneurial resilience have been conducted in high-income countries. In harnessing entrepreneurs for economic resilience and recovery during a crisis, governments have to deter a 'race to the bottom' response and encourage a 'community pulling together' response. The first is a 'dog-eat-dog' race to secure as many of the dwindling resources for oneself as possible. In the second, the community pulls together to buffer its members against the shock. We currently know little about how to promote sustainable responses and discourage unsustainable ones. We address the above knowledge gaps. Collaborating with Wuhan University, UN Economic and Social Commission for Asia (Bangkok), Asia School of Business (Kuala Lumpur) and Asian Development Bank (Manila) we study entrepreneurial firm- and community-level responses and business model practices for resilient adjustment to covid- 19 crisis and for robust post-crisis recovery. We will conduct 20-25 longitudinal case studies to induct firm- and community -level process models of entrepreneurial resilience and recovery to inform policy and entrepreneurial practice in lower and upper middle income economies in Asia.",2021,2022,Imperial College London,332430.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia | Western Pacific,,,,United Kingdom,China | Malaysia | Thailand | Philippines | United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C04116,EP/V028979/1,GCRF_NF100 PPE & Refugees: dealing with a crisis by building livelihoods,"In March 2020 we were contacted by UNHCR for help with PPE in the Zaatari refugee camp, using digital printing and sewing capabilities here at our UK Universities and in the camp. Our immediate response means that this work has already started. In both the UK and Jordan we have made prototypes of masks, shields and gowns and there have been co-created innovations in both design and joining technologies. With Agile Response funds we will run an interdisciplinary co-production project, comprising a socio-technical part focused on designing PPE for production in refugee camps and the host community, and socio-behavioural part, understanding how the availability of PPE affects people's attitudes and behaviours around risk, and so enables them to address health threats. Digital manufacturing and digital data gathering will be central, enabling real-time collaboration even without face-to-face contact. In Jordan - and other lower/middle income countries - there was very limited availability of PPE at the beginning of the pandemic in refugee camps, and UNHCR was only able to source materials for clinical needs. Whilst Jordan has done extraordinarily well in suppressing transmission of the virus, recording 11 deaths from 1100 cases, it has been at only been achieved through the result of a very severe economic and social lockdown and stringent defense laws being invoked. The UNHCR is preparing for Covid19 to a dramatic impact when it comes into densely populated camps, causing community transmission, as lock down is eased. There is a pressing need for supplies of PPE compliant with Jordanian (and other country) standards, yet with limited buying power neither the UN agency nor the government is well-placed to compete globally for supplies. The development need is thus for sustainable local manufacture, using a reliable supply of locally available, low-cost materials to produce PPE appropriate to refugees' needs. Simultaneously, the project will tackle the problem of plastic waste, (including discarded PPE), open employment opportunities in small-scale manufacturing, and build resilience within the camp community by reinforcing a sense of collective agency and capacity. The direct benefits of this research will accrue to the substantial refugee populations in Jordan, with outcomes also applicable to other low resource economies hosting displaced people. Building on existing technical prototyping activities, the project will increase knowledge on successfully producing PPE in the refugee context. The central innovation is to a) co-create the design, manufacture and distribution process with the refugees as partners and thus empowered agents, and b) to thus calibrate the process and outputs to the specific conditions in the camp. The refugee-led social research will address broader questions, currently insufficiently addressed in the literature, of the effects of PPE uptake on refugees' sense of agency, ability and willingness to play a role in preventing and treating COVID-19. We can move swiftly, as we have engineering and social science PDRAs from the UKRI #redefiningsingleuse grant ready and keen to go. In Jordan, UNHCR and Al Albayt University will train participatory action researchers (PARs) to engage in the design, manufacturing, and implementation of comprehensive reusable PPE (initially masks, shields and gowns, moving on to innovations in gloves and hand sanitiser). The University of Petra will use semi-structured interviews and PARs to understand the social/spatial aspect of PPE-associated behaviour in the confined environment of the camp.",2021,2022,University of Sheffield,576591.84,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Eastern Mediterranean,Innovation,,,United Kingdom,Jordan,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Other secondary impacts",2020 +C04117,EP/V029088/1,"GCRF_NF123: COVID-19, social distancing and violence against women in Brazil (BRAVE)","Domestic violence against women (DVAW) is a major issue in Brazil. It tends to disproportionally affect women of disadvantaged backgrounds, putting them at a higher risk of poverty and potentially increasing gender-based inequities. Commentators have linked social distancing measures introduced in Brazil to address the spread of COVID-19 to significant increases in DVAW cases, with similar reports in other countries. COVID-19 cases in Brazil are forecast to keep increasing, likely leading to further social distancing measures in the near future, making our research urgent to understand how policies can better protect vulnerable women and reduce the broader impacts of these measures to society. BRAVE seeks to understand how social distancing measures affect DVAW and assess the resulting societal costs of such effect. To this end, we will analyse information on DVAW and its link to social distancing adherence, poverty and the financial cost of DVAW to victims and society, focusing on Brazilian cities. We will also examine how public policies aimed at mitigating the negative consequences of social distancing influence DVAW, and how these policies could be refined to better address DVAW. We will work closely with both the local academic community and representatives of public and other organisations, to offer guidance to improve public policies for DVAW victims in the pandemic context, for Brazil and potentially other countries.",2021,2022,University of York,160944.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas,,,,United Kingdom,Brazil,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Social impacts | Other secondary impacts,2020 +C04118,EP/V029177/1,GCRF_NF118: Capacity building reliable diagnostic & epidemiological tools to confront the spectre of a COVID-19 epidemic in refugee communities...,"Evidence-led policymaking for COVID-19 control relies on accurate understanding the epidemiology of SARS-CoV-2 infections by correlating diagnostics, molecular fingerprinting and patient metadata (intrinsic (e.g. age), and extrinsic (e.g. travel history)). Efforts to correlate these data in Uganda are stalling, despite available local expertise, because laboratories designated for diagnosing and tracking COVID-19 are under-resourced, and widespread mistrust of diagnostic workflows. Current policy is therefore shaped by data from industrialised countries, which may be misleading due to significant differences in the population demographics and underlying health status. Laboratory facilities in northern Uganda are lacking: i) reagents and experience of reliable workflows for processing of COVID-19 diagnostics; ii) whole genome sequencing equipment and consumables for providing robust epidemiological information. We will address these needs by bringing together UK-based academics and industrial partners with Ugandan biologists and policymakers to rapidly build local capacity for SARS-CoV-2 diagnostics and real-time epidemiology. Specifically: Transfer knowledge of SARS-CoV-2 diagnostic workflows from leading UK testing centres (NHS, Lighthouse Labs) to Uganda. Establish Nanopore sequencing and bioinformatics in northern Uganda, supported by Salford/Liverpool/COG-UK partners, and facilitate their long-term adoption by Ugandan laboratories (UVRI, Makerere University). Combine WGS with new survey-based patient metadata to provide real-time SARS-CoV-2 genomics, including strains circulating around refugee settlements, to support the Ugandan Ministry of Health and Prime Minister's Office to promptly mitigate local and national COVID-19 spread. Bring together industry and logistics partners with Ugandan policymakers, to identify and address bottlenecks in the equipment and consumable supply chain, to support cost-effective, future Ugandan bioscience.",2021,2022,University of Salford,413747.4,Human Populations,Black,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Uganda | South Sudan,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Health Systems Research","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Medicines, vaccines & other technologies",2020 +C04119,EP/V028731/1,GCRF_NF154: Socio-economic and health impact of Covid-19 on international female migrants and their left-behind families in Indonesia,"Rationale: There are about 1.3 million women from Indonesia working abroad, mainly in the Middle East and South East Asia, as maids and carers in private houses. They leave their families in Indonesia. Husbands who live in Indonesia look after their children. Migrant wives send money for family maintenance. Migrant women are generally vulnerable to neglect by employers and recipient countries because of their gender, poor economic situation, work status, nationality. There are no studies on the impact of Covid-19 on migrants' access to health care; job losses; wage cuts; delayed wages; issues around returning home; welfare of left behind family. Reliable data on the impact of Covid-19 are urgently needed for the government to take timely action. Project aim: Study socio-economic and health impact of Covid-19 on international female migrants and their families in Indonesia, and make policy recommendations to the Indonesian government to minimise negative consequences. Evidence needed: Gather data on the impact of Covid-19 on health, economic, and social welfare of migrants and family via household survey, interviews and online survey. Final output: Rapid and final policy recommendation papers for the Government of Indonesia. What are the benefits of this study? Adoption of rapid response recommendation by the Government of Indonesia in to their policy/programme for Covid-19. Enable migrant women to access Covid-19 tests and treatment if needed, economic support to those who need it most, facilitate travel to return home, social support to the migrants and families.",2021,2022,University of Portsmouth,143960.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Western Pacific,Western Pacific,,,,Indonesia,Indonesia,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +C04120,EP/V029193/1,GCRF_NF127 A capabilities assessment of Covid-19 changes to the Workers' Rights Act in Mauritius:implications for domestic and migrant workers,"The COVID-19 (Miscellaneous Provisions) Act 2020 was passed by the Government of Mauritius in May 2020 and will be reviewed in December 2021. Landmark changes were made to the Workers' Rights Act (WRA) 2019 which are impacting both domestic and migrant workers. The hardest hit are workers in tourism and hospitality, textile factories and the informal economy. Examples include reduced compensation, withholding of workers'annual leave, facilitation of justified termination of workers' contracts and exemption from negotiations with workers' organisations (unions) by employers prior to reduction of the workforce (Appleby, 2020). Public policies are critical in providing an environment for the development of capabilities and freedom of choice. We use a capabilities approach to assess the impact of the amended WRA on workers, their opportunity set and their freedom to lead lives they value. We will collect survey data from 1200 domestic and migrant workers from Bangladesh and conduct 50 semi-structured interviews with relevant stakeholders to produce evidence-based datasets for the co-development of a policy brief and detailed report in order to inform the Government's review in December 2021.",2021,2022,University of Strathclyde,168396.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | South-East Asia,,,,United Kingdom,Mauritius | Bangladesh,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C04121,EP/V028936/1,GCRF_NF151 COVID19:Determining trustworthiness and safety of REmote Consulting in primary healthcare (REaCH) for chronic disease populations in Africa,"During the COVID-19 pandemic, face-to-face healthcare appointments puts Africa's health workers and their patients at risk. Patients are afraid to attend clinics, e.g to collect medicines, and this may harm their health. Remote healthcare, by phone or internet, is advised by the World Health Organisation. Because this is difficult in Africa due to limited digital infrastructure, we have developed a training programme for health workers called REaCH. REaCH enables health workers to deliver trusted and safe care using the phone and limited internet availability. REaCH training aims to increase the number of appointments held by phone for patients with long-term conditions. We want to test whether these remote appointments are as acceptable, safe and trustworthy as face-to-face appointments. We will undertake trials in Nigeria and Tanzania. In each country we involve 20 health clinics and train 8-10 health workers in two clinics every month for 12 months. We collect monthly information on appointment type and the number of prescriptions and investigations given out. Twenty patients in each clinic per month will complete questionnaires on 1) how trustworthy they found their health worker to be and 2) how confident they are in managing their own health. Patients, clinic health workers and managers will be interviewed. We will produce a) Strengthened health care across Africa following REaCH training b) health workers and patients protected from coronavirus/COVID-19 c) stronger scientific research teams in Nigeria and Tanzania.",2021,2022,King's College London,1080893.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,Digital Health,,,United Kingdom,Tanzania | Nigeria,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C04122,EP/V029118/1,GCRF_NF143 Barcoding Galapagos: Recording and mitigating Covid-19 impacts using key-workers in eco-tourism,"The diversity of life in a given area, its biodiversity, is fundamental to the stability and function of the ecosystem within that area, as well as to the services it can provide, including eco-tourism. However, we generally have limited knowledge of the constituents of biodiversity, with implications for our understanding of ecology and evolution, and the implementation of conservation. For example, even for conspicuous animals, such as birds, history has taught us that it is difficult to define a species based on traditional methods of grouping around morphology or song. By revealing hidden variation, molecular genetics has, more recently, exposed hundreds of new species of birds, and there are thought to be hundreds more to be discovered. In addition, molecular methods allow us to detect connectivity between populations, identify sub-species or races and uncover the genetic signature of individuals within a specific area. In turn, these allow us to study speciation in action, recognise threats to population viability, inform captive breeding programmes and even spot individuals that are illegally trafficked or caught. Finally, molecular tools are the fastest method of identifying plankton, the engine of our seas, and are the only viable means of estimating the number and signatures of species at the base of the tree of life (e.g., microbes). We propose to barcode the unique biodiversity of Galapagos, the inspiration for amongst the greatest scientific revolutions in history - Charles Darwin's theory of evolution by natural selection. Today, this Natural World Heritage site (est.1976) and UNESCO Biosphere Reserve (est.1984) not only continues to help us understand the process of evolution by natural selection, but also inspires pioneering models of sustainability, conservation and ecotourism. Such models are celebrated for their long-term solutions to existing tensions between the preservation of biodiversity and the social-economic well-being of local inhabitants. However, the Covid-19 pandemic has revealed their vulnerability to short-term perturbation. The consequence of this vulnerability is obviously far-reaching for a community wherein 80% are reliant on tourism. This not only means that the biodiversity from which we have learned so much and upon which the Galapagos' relies for its ecotourism industry, is under imminent threat from harvesting, but also that the naturalist guides, who are the 'eyes' of the park and disseminate Darwin's legacy to the 275,000 tourists annually, have lost their income. Our vision is to train and employ 84 naturalist guides to catalogue the biodiversity of Galapagos, from microbe to mammal, using 21st century genetic barcoding approaches. This 'Barcode of Life' project will ensure that: (1) the genetic profile of Galapagos is documented and curated so that the direct and indirect impacts of environmental perturbations can be quantified; and (2) naturalist guides, who are central to economic recovery for a population almost entirely reliant on ecotourism, receive immediate capacity-building employment. Throughout, we will (3) record the socio-economic consequences of our approach at the level of individuals and the community in order to guide future attempts at using locally-driven research to improve the socio-economic well-being and resilience of key workers in the ecotourism industry. Our project partner, the Galapagos Conservation Trust, will ensure that our initiative is widely publicised and discussed in schools, in the local community and with the numerous stakeholders (including National Parks, Biocontrol Agency, and the numerous NGO's working in the Galapagos). This novel initiative to barcode an ecosystem puts science at the forefront of socio-economic well-being, and acts as an important reminder of the long-term benefits of sustainable natural resources for employment and education.",2021,2021,University of Exeter,611909.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Ecuador,Ecuador,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C04134,unknown,Eur3ka EUropean Vital Medical Supplies and Equipment Resilient and Reliable Repurposing Manufacturing as a Service NetworK for Fast PAndemic Reaction,RAPID REPURPOSING OF MANUFACTURING FOR VITAL MEDICAL SUPPLIES & EQUIPMENT -,2020,-99,Engineering Ingegneria Informatica Spa,7038870.77,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Eastern Mediterranean | Europe,,,,Italy,Switzerland | Denmark | Germany | Spain | Finland | Israel | Italy | Luxembourg | Netherlands | Norway | Portugal,Health Systems Research,"Medicines, vaccines & other technologies", +C04150,unknown,"SHARE-COVID Non-intended health, economic and social effects of the COVID-19 epidemic control decisions: Lessons from SHARE","BEHAVIOURAL, SOCIAL AND ECONOMIC IMPACTS OF THE OUTBREAK RESPONSES - The non-intended consequences of the epidemic control decisions to contain the COVID-19 pandemic are huge and affect the well-being of European citizens in terms of economics, social relationships and health: Europe is experiencing the largest recession since WWII; social contacts have been interrupted; people avoid seeking medical treatment in fear of infection. The overarching objective of this project is to understand these non-intended consequences and to devise improved health, economic and social policies. In our policy recommendations, we strive to make healthcare systems and societies in the EU more resilient to pandemics in terms of prevention, protection and treatment of the population 50+, a most vulnerable part of the population. The project aims to identify healthcare inequalities before, during and after the pandemic; to understand the lockdown effects on health and health behaviours; to analyse labour market implications of the lockdown; to assess the impacts of pandemic and lockdown on income and wealth inequality; to mitigate the effects of epidemic control decisions on social relationships; to optimise future epidemic control measures by taking the geographical patterns of the disease and their relationship with social patterns into account; and to better manage housing and living arrangements choices between independence, co-residence or institutionalisation. The project pursues a transdisciplinary and internationally comparative approach by exploiting the data sources of the SHARE research infrastructure. It covers all EU MS. The project's team represents medicine, public health, economics and sociology and has worked together since the creation of SHARE. It is experienced in translating data analysis into concrete policy advice. The project's policy recommendation are targeted at policy makers in the Commission and in national ministries as well as at national and international NGOs and social organisations.",2020,2023,Max-Planck-Gesellschaft zur Förderung der Wissenschaften (DE),7993866.55,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Eastern Mediterranean | Europe,,,,Denmark,Czech Republic | Germany | Denmark | Greece | Spain | France | Croatia | Israel | Italy | Netherlands | Poland | Sweden,"Research to inform ethical issues | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Economic impacts",2020 +C04162,1.043E+13,Population differences in diagnosed covid-19 prevalence in the Netherlands. Which groups are at highest risk?,"Project description Which people are most at risk for the coronavirus? Why this research? It is said that everyone is at the same risk of contracting the coronavirus (COVID-19). Still, some population or occupational groups seem to be infected more often than others. What is being studied? n this study, it is examined which people have tested positive for the corona virus more often than others. This could include people with a certain profession or a very low income. The influence of the circumstances in which people live or work on the risk of becoming ill is also examined. This could include the size of a family or the living space. Count and tell Figures only tell part of the story. That is why discussions will also be held with people themselves. In this way they can indicate what could help them to stay healthy. The ultimate goal is to fight the corona virus in a fair (er) way.",2020,2021,GGD Zuid Holland Zuid,91743.63,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C04163,unknown,A multidisciplinary guide for people with disability using ICT for social contact to mitigate impact of restricted in-person visit policies,Focus area 2. Care and Prevention Theme 1: Organisation of care and prevention,2020,-99,VU Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,Digital Health,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts, +C04164,1.043E+13,"A phase-2-study, pivotal for clinical development of lanadelumab for treatment of COVID-19","Project description COVID-19 can lead to fluid in the lungs causing oxygen deficiency. When this is present for a long time, it can lead to intensive care (IC) admission and eventually death. There are indications that the virus disrupts the regulation of blood vessel wall permeability because the virus reduces the function of the protein angiotensin converting enzyme 2 (ACE2). As a result, produced quinines can no longer be broken down at the site of the infection. Quinines can make the blood vessel wall permeable to moisture. Research and expected outcomes This study investigates whether inhibiting the production of quinines with the drug lanadelumab can lead to a rapid recovery from oxygen deficiency. The aim of this treatment is to prevent an ICU admission if patients are admitted to hospital and have signs of fluid in the lungs and oxygen deprivation. If there is a clear effect, the strategy to inhibit the quinine system in COVID-19 will be investigated in larger trials.",2020,2021,Radboud University Medical Center,548813.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C04165,1.043E+13,A virus-free high-throughput platform for studying coronavirus replication inhibitors,"Focus area 1. Predictive diagnostics and treatment Theme 4. Virus, immunity, immune response and pathogenesis",2020,2021,Amsterdam University Medical Center - location AMC,229533.68,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,Innovation,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C04166,1.043E+13,Altered IgG fucosylation driving pathologies in COVID-19: Relevance for diagnosis and therapeutics,"People who become infected with COVID-19 react very differently. Some do not notice it, others show mild symptoms and some become seriously ill. Typically, people with complaints either heal or get worse after about a week after infection. This is accompanied by the activation of the adaptive immune system, which is then able to clear the virus. Unfortunately, this immune activation appears to be too intense in some patients. The cause of this is unclear. Research and expected outcomes Research indicates that an important functional switch in antibodies - the sugar fucose - is 'on' in some viral infections, including in critically ill COVID-19 patients, and not in people with mild complaints. In this project, the development of this type of response and its influence on antibody (plasma) therapies in patients is studied. The results will hopefully lead to a more efficient and safer use of antibody-based therapies.",2020,2022,Sanquin (Blood Supply),455912.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C04167,1.043E+13,BCG vaccination to minimise COVID-19 disease severity and duration,"Project description Mycobacterium bovis is the bacteria that causes tuberculosis in cows. The BCG (Bacillus Calmette-Guérin) vaccine consists of attenuated bacteria of this strain. Almost 100 years ago it was discovered that BCG protects against human tuberculosis. In recent years it has been shown that BCG also protects against other infections by activating the immune system in a broad sense. BCG has the potential to protect against COVID-19. Research This study investigates whether BCG can reduce the incidence, severity and / or duration of COVID-19. The impact of BCG on the development and lifespan of COVID-19 antibodies, the immune system in a broader sense and the microbiome composition of the airways is also investigated. Expected outcomes Should BCG be effective, it could be used to protect risk groups until COVID-19-specific vaccines become available. In that case, BCG could also be used in future epidemics due to new pathogens.",2020,2022,University Medical Center Utrecht,548908.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C04168,114025010,Blood Vessels-on-Chip to Understand and Target COVID-19,"Project description When COVID-19 patients become seriously ill, they often have problems in their blood vessels. This is how we see leakage, inflammation and blood clotting. In this project, a mini-blood vessel based on human vascular wall tissue and COVID-19 patient plasma is used to study blood clot formation. It is not yet clear why vascular problems occur in COVID-19 and whether they offer starting points for treatments. Finding answers to these questions is made difficult because laboratory animals infected with the SARS-CoV-2 virus do not develop complications in their blood vessels. It is therefore essential to perform this research using human tissues. In the project, researchers from the University of Twente will build and analyze the mini-blood vessels. Researchers from the Amsterdam UMC will collect and characterize the patient plasma for these models. Experts from the LUMC will perform molecular biological analysis on the cultured tissues.",2020,2022,University of Twente,273541.19,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C04169,1.043E+13,BTK inhibition to prevent hyperinflammatory syndrome in COVID-19 patients,"Project description About 5% of all COVID-19 patients become seriously ill and must be admitted to intensive care. This patient group often develops serious damage to organs and has a high risk of death. This is because certain cells of the immune system, especially the monocytes, overreact to the virus. This is also called a hyper-inflammatory syndrome. The protein Bruton's tyrosine kinase (BTK) is involved, among other things, in monocyte activation and can be inhibited by the specific BTK inhibitor acalabrutinib. Other cells that are very important for killing the virus, such as T cells, are not affected by BTK inhibitors. Research and expected outcome This study will investigate whether acalabrutinib treatment indeed leads to clinical improvement in admitted COVID-19 patients. In addition, the effects of acalabrutinib on the various cells of the immune system are identified in order to gain knowledge about the mode of action of acalabrutinib in COVID-19 patients.",2020,2020,Erasmus Medical Center,431957.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C04170,1.043E+13,Caring and waving: longitudinal study on the consequences of restrictive COVID-19 measures for relatives of people with intellectual disabilities and their need for support,"Project description During the corona crisis, relatives of people with an intellectual disability had to deal with the visiting arrangement in care institutions (waving) or that the family member came to live at home (care). Care, support and daytime activities often decreased, and contact with other people also decreased. There will be many changes for loved ones and their relatives in the coming period. Questionnaires and interviews are used to investigate the consequences of the corona measures on the quality of life of loved ones and on the care and support they provide. It is also examined which support family members receive and need themselves. The aim of the study is an improved approach to loved ones in the coming period. In 2020 and 2021, questions will be asked to loved ones at three times. The research is carried out together with an expert by experience and those involved in care for the disabled. In addition to the dissemination of knowledge, recommendations are also made for professionals and policymakers, among others.",2020,2022,NIVEL,134906.18,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04171,1.043E+13,Changes in the use and organization of care in general practice and out-of-hours services: lessons learned from the COVID-19 pandemic,"Project description Since the start of the corona pandemic, much has changed in the organization of care, including in general practitioner care via the GP practice and the general practitioner post (HAP). Healthcare use has fallen sharply in some regions, while other regions were faced with high numbers of patients with COVID-19 complaints. Insight into the impact of these changes on health care use - both during and after the corona pandemic - can contribute to resilience and sustainability in the organization of health care in the future. The research is a collaboration between Nivel and the UMCG. Routine care data from the electronic patient files of the general practices and the HAP are analyzed to map the use of care. These will, with specific attention to vulnerable groups in our society, be related to: Organizational changes Experiences of patients and healthcare professionals obtained from interviews Questionnaires and information about the use of Thuisarts.nl",2020,2022,University Medical Center Groningen,548613.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health workforce,2020 +C04172,1.043E+13,"Clinical prediction models for COVID-19: development, international validation and use","Project description To be able to estimate the expected course of their disease is crucial for good care for COVID-19 patients. For example: should someone be admitted to intensive care (IC) and for how long? What is the probability of death? Research In this research, prediction models are developed that provide an answer to these questions upon admission to the hospital. Data is used for this from more than 4000 patients from seven Dutch hospitals. The models use a limited number of factors that are easily measurable, such as respiratory rate, so that the model is easy and direct to use in all Dutch hospitals. Discussions will also follow with care providers, patients and family members about how the models best meet their wishes. The model is available as decision support in a web application: https://mdmerasmusmc.shinyapps.io/COPE/ . Desired outcomes The prediction models can then be used by healthcare providers to make decisions about the optimal care for the patient in consultation with patients and their families. Results: https://doi.org/10.1101/2020.12.30.20249023",2020,2021,Erasmus Medical Center,171319.2,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C04173,1.043E+13,"Consequences of restrictive measures because of COVID-19 outbreak on loneliness and social needs of residents, informal caregivers and volunteers in nursing homes","Project description Protective measures were taken in nursing homes during the COVID-19 outbreak. These measures affect the lives of the residents, their loved ones and volunteers. This project investigates the loneliness experienced by people, but also the social needs and resilience of residents, loved ones and volunteers. The results can be used to minimize the consequences of a second outbreak of COVID-19. What should be taken into account in policy to mitigate consequences? Which ethical issues play a role in this? Answers to these questions are sought through interviews and group discussions with residents, relatives and volunteers. The research is carried out by academic networks for elderly care in Tilburg, Groningen and Leuven. A sounding board group with representatives of the elderly, relatives and volunteers actively participate in the research.",2020,2022,Tilburg University,385646.11,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04174,1.043E+13,CONTROL (CONtact TRacing OptimaLisation): effectiveness & optimalisation of source investigation and contact tracing to limit spread of SARS-CoV-2,"Project description Source and contact research (BCO) is very important to limit the spread of the coronavirus (SARS-CoV-2). In order to research and improve the effectiveness of BCO, seven GGDs (Amsterdam, South Limburg, Rotterdam-Rijnmond, Groningen, Flevoland, Hart voor Brabant, Utrecht Region) and the RIVM-CIb are starting a joint scientific project: CONTROL. CONTROL will evaluate the process and the effectiveness of the BCO. It is examined which characteristics of people with the coronavirus and of their contacts determine the turnaround time and the effectiveness of the BCO. Barriers and success-determining factors for the BCO are identified in consultation with field parties and an improvement plan is drawn up. It is also investigated which factors are predictive of further virus spread. In addition, a tool is being developed to perform BCO quickly and intensively in people with the coronavirus who can potentially infect many others.",2020,2022,GGD Amsterdam,548164.33,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2020 +C04175,1.043E+13,COVID-19 and ischemic stroke - How to tame a dozing monster,"Project description Patients with COVID-19 pneumonia, especially when admitted to intensive care, may develop thrombotic complications that may contribute to a more serious course of COVID-19 pneumonia. Pulmonary embolism (clot in the lung) is the most common complication, but stroke can also occur. The hypothesis in this study is that these strokes may be caused by coagulation activation and inflammation of the arteries, or that they are the result of a blood clot entering the brain vessels from the leg or pelvic vessels through an open connection between the right and left sides of the heart. ends up. Research and expected outcomes In three work packages, knowledge is obtained about: an accurate estimate of the occurrence of ischemic stroke in COVID-19 IC patients. the causes and consequences of strokes based on imaging studies and lab tests. the optimal prevention of strokes by examining the effect of different treatments.",2020,2022,Leiden University Medical Center,549036.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C04176,844001802,"CovId-19 and SOcial isoLATion in dEmentia care (ISOLATE): impact and needs of people with dementia, informal and professional caregivers","Project description The COVID-19 measures on social isolation appear to have a major impact on the well-being of people with dementia, informal carers and care workers. While loneliness and problematic behavior increase in people with dementia, social support for informal carers is declining and they are burdened with additional burden. In addition, rules regarding physical distance complicate the work of care workers. Research This project investigates the impact of social isolation on intra- and extramural dementia care by interviewing informal carers and care workers. Expected results Problems, concerns and needs are mapped in order to improve social well-being during social isolation for people with dementia, their informal caregivers and care workers within the intra- and extramural setting. Expected impact This research makes an important contribution to the still limited knowledge about the impact of social isolation in care for people with dementia and makes policy proposals to improve care and welfare.",2020,2022,Leiden University Medical Center,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04177,1.043E+13,"COVID-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: a combined rehabilitation, pulmonary, and intensive care perspective (CO-FLOW study)","Project description Background After hospital discharge, COVID-19 patients follow various aftercare paths, for example in a rehabilitation center, nursing home, or physiotherapy practice. We still know little about the eventual recovery after COVID-19 and the effect of these aftercare pathways. Target Mapping the long-term consequences of COVID-19 and further developing the aftercare paths. Method COVID-19 patients who have been admitted to hospital in Rotterdam-Rijnmond will be followed for 2 years. A lot of data is collected, such as patient flows, health care use and (predictors of) physical, cognitive and psychological recovery. What are the benefits? It is expected that patients who have experienced COVID-19 after hospital discharge may experience complaints in various areas for a long time. The research provides insight into the long-term consequences of COVID-19 and the aftercare is better tailored to the patient.",2020,2023,Erasmus Medical Center,548359.81,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C04178,1.043E+13,Data-driven Simulation Games for the Evaluation and Prevention of SARS-CoV-2 Transmission in Indoor Public Spaces and the Impact of Changing Compliance to Distancing Measures,"Project description Indoor spaces (restaurants, offices, shops, etc.) play an important role in the spread of SARS-CoV-2. That is why compliance with regulations, especially in these areas, is of great importance. This study examines how effective the measures are for reducing the spread of SARS-CoV-2 in indoor spaces with reduced compliance. The researchers will combine virological and epidemiological data to better understand the spread of the virus in indoor spaces. The changing compliance with rules will be investigated with data from crowd monitoring systems from before, during and after the 'intelligent lockdown'. Using a simulation game, based on this data, the spread of SARS-CoV-2 in indoor spaces is investigated for a large number of scenarios and in the event of changing compliance with rules.",2020,2022,Wageningen University & Research,411428.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C04179,1.043E+13,Effect of COVID-19 on GP care use by underrepresented patients in deprived neighbourhoods,"Project description The pressure on GP practices in deprived neighborhoods is great due to the health problems of residents and low self-reliance. Due to the spread of COVID-19, GP practices offer remote care: telephone consultations, video calling, e-health. These concerns and thresholds for GP visits by COVID-19 may have major consequences for vulnerable groups. Research must clarify for which groups remote care is suitable and where space is created for patients who need more care. For this, the experiences with the changed way of working are mapped. The GP practices participate in interviews and keep diaries. They also register the use of the GP by patients. The research is divided into different phases, making it possible to use interim insights in a revival of the virus. General practitioners are actively involved in the research, so that the knowledge acquired can be applied immediately.",2020,2022,Erasmus University Rotterdam,263846.94,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C04180,114025011,Employing a physiological microfluidic lung bioreactor to improve understanding of SARS-CoV2 biology and testing of therapeutics,"Project description The COVID-19 pandemic has made it clear that acting quickly is important to adequately combat global health problems. In addition to rapidly identifying and treating patients, it is important to develop good methods to understand infection mechanisms and develop vaccines. This project aims to grow human lung cells in a mini bioreactor to simulate the physiology of lungs as much as possible. Airway 'epithelial' cells and blood vessel lining 'endothelial' cells will be simultaneously grown in the bioreactor, forming an artificial airway and blood vessel, respectively, along which air and growth medium flow. This system is closer to reality than currently available testing methods and will mimic viral infections better. With our system, promising drugs can be tested quickly. In addition, the bioreactor can be made on a commercial scale, and its simplicity will make it easy to implement.",2020,2022,Erasmus MC-Sophia Children?s HospitalǨǨ Ǩ,582046.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C04181,1.043E+13,"Establishment and duration of protective immunity against SARS-CoV-2, in relation to severity of SARS-CoV-2 infection","Project description In most people, a specific immune response can be demonstrated after a COVID-19 infection. However, it is not known how long and how well this immune response protects against re-infection. This can be investigated at Sanquin because blood is regularly collected from 300,000 blood donors, some of which is also stored for two years. Research For donors who have had COVID-19 disease - from asymptomatic to seriously ill - the course of COVID-19 antibodies in the serum and (in a subgroup) the memory cells will be analyzed for two years. To what extent an immune response protects against re-infection is prospectively investigated in 2000 antibody positive donors. In addition, all people who are tested positive for COVID19-PCR from September 2020 will be checked to see whether they are blood donors. The plasma of these people, which was frozen around July 2020, will then be tested. Expected outcomes If a previous infection protects, it is expected that much fewer anti-COVID-19 antibodies are found in the COVID-19-PCR positive group than in the control group.",2020,2022,Sanquin Research,494303.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C04182,114025009,Ex vivo models to study tissue-specific features of SARS-CoV-2 infection,"Project description Infection with coronavirus not only leads to problems in the respiratory tract, but also in other organs. However, little is known about how the coronavirus infects various organs. In this project we therefore study how the coronavirus manifests itself in different organs. In addition, the research focuses on simulating coronavirus infections in cultured miniature organs in the laboratory. In these mini-organs we can study in great detail how the coronavirus infects cells and which molecular pathways it uses for this. We hope that these human cell models can contribute to improving the diagnosis and treatment of coronavirus infection, while also reducing the use of laboratory animals.",2020,2022,University Medical Center Utrecht,518980.77,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C04183,unknown,Healthcare utilization in primary care during the corona pandemic: a nation-wide population-based study from a patient and healthcare provider perspective,"Project description Question During the COVID-19 pandemic, people have started to avoid healthcare. In addition, the care capacity has changed due to the measures. Decreases in the use of (regular) primary care can lead to health damage due to, for example, late-diagnosed or untreated heart and vascular diseases or oncological conditions. Research This research provides insight into the use of primary care during the COVID-19 outbreak. It reveals which care demands are being postponed by patients and / or care providers, it identifies groups at risk and finds out the actual reasons for care avoidance. Expected outcome Results of this study contribute to the development of strategies to mitigate declines in health care use in potential flare-ups of COVID-19. Moreover, the research provides tools for policymakers so that they can weigh up new preventive measures against possible side effects.",2020,2022,Erasmus Medical Center,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04184,1.043E+13,Homeless and COVID-19 - lessons for the future,"Project description Homeless people often have poor health. They have a high chance of becoming very ill from Corona. They usually do not visit ordinary GP practices, but they do visit street doctors. It is not known how often they get Corona or what the consequences of Corona measures are for them. Therefore, research is being done to find out the following: How often and how badly homeless people get Corona What other problems they come to street doctors with What are the consequences of the Corona measures How municipalities have applied the Corona measures in the shelter Corona causes more homelessness For this, interviews are held with homeless people, civil servants and social workers. Information is collected from street doctors about patients with Corona and their care for other patients. Furthermore, together with homeless people and other parties involved, advice is being devised for the minister and for social services, so that this research contributes to good care and shelter for homeless people in the future.",2020,2022,Radboud University medical Center,256884.35,Human Populations,Unspecified,Unspecified,Unspecified,Other,Social Workers | Caregivers | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C04185,1.043E+13,ICU triage during a crisis: learning from the application of medical and non-medical criteria to patient cases,"Project description Suppose all intensive care beds (IC beds) are occupied during a pandemic, how is a fair choice made between patients for whom such a bed is necessary care if one bed becomes available? In the Netherlands, medical and non-medical criteria are used in such a situation. These criteria are included in some scripts, but experience with applying them is lacking. This project aims to tackle the problem by simulating triage with the established criteria through retrospective case histories. What considerations play a role when triage teams apply the criteria? What can be learned from this in preparation for the next crisis? The results are presented to a wide group of stakeholders to gauge public support. Based on the research, e-learning is being developed to help doctors (in training) and aims to better prepare members of triage teams for triage in the event of a shortage of ICU beds.",2020,2022,Radboud University Medical Center,261338.65,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C04186,1.043E+13,Identification of COVID-19 patients with high Risk of mortality at ICU admiSsion - IRIS-study,"Project description Deciding which COVID-19 patients will benefit most from intensive care unit (IC) treatment is an important societal issue. New COVID-19 patients are admitted daily. Care for non-COVID-19 patients must also continue. The pressure on IC capacity became very high during the COVID-19 peak in the spring of 2020, which could be repeated in the next wave. Research and expected outcomes This study looks at patient characteristics that indicate an extremely long IC admission or a very high risk of death for the patient. Intensivists, other specialists, the patient and family members can use this knowledge to jointly make informed decisions about the usefulness of an IC admission. The research uses three data registers ( NICE foundation , CovidPredict and Vektis ). Together, the registries include all IC patients in the Netherlands, including detailed and long-term outcome information for COVID-19 patients. Analyzes are done by means of statistical and machine learning techniques.",2020,2022,Nationale Intensive Care Evaluatie,257165.49,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Prognostic factors for disease severity,2020 +C04187,1.043E+13,Identifying pathogenesis of COVID-19 pathology in the Dutch population and unravelling differences in pathogenetic mechanisms in high- and low-risk groups,"Project description COVID-19 has a striking variation in disease severity between patients. There is so far insufficient knowledge about which processes in the tissue are the cause of this variation. This limits the development of targeted diagnostics and therapy for individual patients. Tissue studies in COVID-19 patients may change this, as the tissue can distinguish between direct virus-induced damage, out-of-control inflammation, increased coagulation, and scarring, all of which may require different treatment. need. Research and expected outcomes Within the framework of this project, the tissue available and suitable in the Netherlands from both deceased and living COVID-19 patients will be collected to be able to ask and answer these questions. The results are expected to lead to improved understanding of the variability of this disease and lead to more personalized treatment.",2020,2022,Erasmus Medical Center,526491.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Disease pathogenesis,2020 +C04188,1.043E+13,Immunity against SARS-CoV-2 in immune-suppressed patients: increased risk of insufficient immunological memory or sufficient protection against re-infection?,"Patients with autoimmune diseases often use immunosuppressive medication. The effect of these treatments on the development and maintenance of adequate immunity after a previous COVID-19 infection and on the upcoming vaccines against Covid-19 is unknown. Research and expected outcomes First of all, COVID-19 specific immunity is investigated in patients and healthy people after a previous COVID-19 infection. In the second phase, the response to a COVID-19 vaccination is compared between infected patients and healthy people. In addition, this response is compared to patients and healthy people without prior COVID-19 infection. With these results, the hope is to determine the effect of different types of immunosuppressant medications on immunity to COVID-19, so that advice can be provided on the optimal vaccination strategy in the many immunosuppressed patients. This study is a collaboration between several university centers, Sanquin Blood Supply and the RIVM (Target to B consortium, T2B).",2020,2021,Amsterdam University Medical Center - location AMC,320331.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C04189,1.043E+13,Impact of COVID-19 on children and adolescents with autism spectrum disorder (ASD) and their family,"Project description COVID-19 and the measures it has taken have a major impact on families with children with autism spectrum disorder (ASD). Children and young people with ASD often experience difficulty with social communication, changes, and unclear social rules. In order to keep the children in the social life and educational landscape as much as possible, a detailed and specialized care network has often been built around the children. This study examines the following in the children and their parents: The psycho-emotional impact The risk and protective factors Care and information need More than 600 families are approached via three mental health institutions in the Rotterdam region to report their experiences in questionnaires and interviews. The data is compared with control data from Generation R, a general population cohort. The mixed-method approach provides both an evaluation of current COVID-19 measures and a starting point for future policy on life-changing events.",2020,2021,Erasmus University Rotterdam,134911.67,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2020 +C04190,1.043E+13,"Improvise, adapt, overwork? Understanding and learning from hospitals' adaptations to COVID-19 and their effects on professional functioning and recovery.","Project description The COVID-19 pandemic is forcing hospitals to adapt their daily work habits. These adjustments take place under great pressure, without it being clear which ones work well and which ones have a negative effect. This can have major consequences for the functioning of hospitals and their staff. This project therefore examines which adjustments hospitals are making during the COVID-19 crisis, which are or have been successful, how these adjustments come about and how they are implemented. In addition, the project investigates the effects of these adjustments on the functioning of healthcare personnel. The emphasis is on the sustainable employability of healthcare personnel and their daily recovery after work. Finally, the best practices identified throughout the project are shared with hospitals across the country and published internationally. In this way, the project contributes to an agile and COVID-19 resistant care system.",2020,2022,Maastricht University,541866.16,Other,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Health Systems Research,Health service delivery | Health leadership and governance | Health workforce,2020 +C04191,114025008,Inhalation of Low Molecular Weight Heparins as a prophylaxis to prevent SARS-CoV-2 infection,"Project description Existing drug prevents SARS-CoV-2 infection There is a very urgent need for SARS-CoV-2 preventive drugs to stop the COVID-19 pandemic. We have found that infection of cells with SARS-CoV-2 is blocked by the anti-clotting drug low molecular weight heparin. This drug blocks the binding of the virus to the cells, which greatly reduces or even prevents infection.In this project we will investigate whether inhalation of low molecular weight heparin can be used as a preventive drug against SARS-CoV-2. To this end, we have developed animal-free innovations to determine the effectiveness of the intervention and to unravel the mechanism of action of this drug.",2020,2022,Amsterdam UMC (location AMC),634490.21,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C04192,1.043E+13,Integrative analysis of multi-omics longitudinal data to identify effective strategies for the prediction and treatment of COVID-19,"Project description Some of the COVID-19 patients develop very severe respiratory symptoms, while others experience mild flu-like symptoms. While it is clear that genetic and non-genetic factors influence the severity of the disease course, the underlying molecular mechanisms are unknown. As a result, disease progression cannot be predicted for an individual at this time. Research and expected outcomes This project aims to gain more insight into the disease and to predict its course by using long-term measurements of multi-omics data. The ultimate goal is to develop a treatment strategy for individual patients.",2020,2022,Radboud University Medical Center,548510.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C04193,1.043E+13,"Measuring, understanding & reducing respiratory droplet spreading","Project description In order to contain the COVID-19 pandemic, it is important to prevent the spread of the deadly coronavirus. The spread of the virus occurs through small droplets of virus particles when talking, coughing, singing, etc. Unfortunately, not much is known about these small droplets. That is why the authorities now use the 'social distance' rule. Research and expected outcomes The aim of this research is to measure and understand the release and distribution of breath droplets when someone talks, coughs, sings, shouts and breathes. In addition, it is investigated to what extent masks contribute to the prevention of the spread of breath droplets. The researchers hope to use the results of this study to provide answers about the usefulness of wearing mouth masks and to find good strategies for ventilation.",2020,2022,University of Twente,549040.7,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C04194,1.043E+13,National and regional coordination in times of scarcity,"Project description The corona pandemic quickly led to a shortage of intensive care beds (IC beds) and a worldwide shortage of materials and equipment. National and regional coordination has been shaped under great pressure. Although this has succeeded in staying within the (highly scaled up) IC bed capacity, a lot has also gone wrong. Moreover, there is also increasing scarcity in health care outside the crisis. Both in times of crisis and beyond, scarcity can be offset by pooling the capacity and resources of several healthcare institutions. However, it is not easy to set up the necessary coordination effectively. This project examines how this coordination can best be designed. This is done on the basis of interviews with key stakeholders and by analyzing available data on the availability and utilization of capacity and resources.",2020,2022,University of Groningen,163496.72,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Health Systems Research,Health leadership and governance,2020 +C04195,1.043E+13,Obesity as an amplifier of inflammation and organ injury in SARS-CoV-2 infected patients: prognostic potential and therapeutic target Thema 3:  Risicoanalyse en prognostiek,"Project description Recent research shows that 77% of the COVID-19 patients who were treated in a Dutch Intensive Care Unit (IC) were overweight. There is some evidence that there is a positive correlation between obesity and the severity of COVID-19. Why overweight people often come to the ICU with severe symptoms of COVID-19 is not yet known. Research and expected outcomes This study investigates the underlying molecular mechanisms behind the reinforcing role of excess adipose tissue on the response of the COVID-19 patient. It is investigated exactly how excess adipose tissue contributes to the development of organ failure, especially failing lungs and kidneys. Once these mechanisms behind COVID-19-mediated organ failure are understood, new drug therapies can be developed to combat organ failure.",2020,2022,University Medical Center Groningen,502281.54,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C04196,1.043E+13,Prospective cohort study of non-hospitalised COVID-19 patients: determining length of isolation and patient clinical development at home (COVID-HOME study),"Project description The UMCG conducts research among COVID-19 patients who have not been admitted to a hospital and their family members. The researchers want to gain more insight into the impact and consequences of the disease on these patients and their families, in order to be able to use this information to make guidelines for the treatment of COVID-19 patients at home. Study Positively tested individuals are visited at home weekly to obtain clinical and laboratory data. This is done by, among other things, taking a nose / throat swab (cotton swab) and drawing blood. To see if the virus is spreading through other routes, urine, faeces and semen or vaginal swabs are also collected. Nose and throat swabs are also taken from family members of positively tested persons to determine whether and when they become infected. Importance The necessity and importance of this investigation is great in the current phase of relaxation of all measures and the possible new outbreaks that may result. The research is carried out in collaboration with the GGDs.",2020,2021,University Medical Center Groningen,900173.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis,2020 +C04197,1.043E+13,ReCOVer: A randomized controlled trial testing the efficacy of cognitive behavioural therapy for preventing chronic postinfectious fatigue among patients diagnosed with COVID-19 disease,"Project description Some of the patients who have undergone COVID-19 have complaints. One of those complaints is fatigue. This is often serious and limits people's functioning. Cognitive behavioral therapy can help with severe fatigue that develops during an illness. Behavioral therapy teaches people to deal with complaints differently. Research This project investigates whether behavioral therapy given via the internet also helps with fatigue after COVID-19. By treating faster after the complaint has arisen, it is hoped that the fatigue will not become chronic. There are 114 patients who are hampered by severe fatigue after COVID-19. Half receive behavioral therapy, the other half receive usual care. Coincidence determines which group a participant enters. The treatment lasts four months, with people being examined immediately afterwards and six months after the treatment. Expected outcome By comparing both groups, it is investigated whether behavioral therapy leads to a reduction in fatigue and disability, and whether fewer people become chronically tired after COVID-19.",2020,2022,Amsterdam University Medical Center - location AMC,338594.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2020 +C04198,1.043E+13,SARS-CoV-2 transmission in secondary schools and the influence of indoor environmental conditions,"Project description Much is still unknown about the role of secondary schools in the transmission of SARS-CoV-2, but various circumstances make the risk of spread very real; Pre- or asymptomatic adolescents can spread the virus unnoticed through direct or indirect contact or through exhaled small droplets in the air ('aerosols'). The role of SARS-CoV-2 diffusion via the air is still uncertain, but may be relevant for conditions in schools with regard to air quality and ventilation. This project aims to quantify the SARS-CoV-2 spread in secondary schools this fall. The degree of diffusion via different transmission routes is studied in detail and related to the quality of the indoor environment and the occupancy in classrooms. This project will also specifically investigate the potential for SARS-CoV-2 aerosol transmission under various experimental conditions in lab studies and relate this to the observations in schools.",2020,2022,Delft University of Technology,549100,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Infection prevention and control,Disease transmission dynamics,2020 +C04199,1.043E+13,"SARSLIVA and utility of saliva in diagnosis for wide scale testing, including viral and SARS-CoV-2  antibody detection in pre- and asymptomatic persons and follow-up of infections in COVID-19 patient; a house hold study","Project description Is it possible to detect the new coronavirus COVID-19 in saliva instead of with a nose and throat swab (cotton swab)? And is it also possible to detect antibodies against the virus in saliva instead of blood? This is being investigated in patients with COVID-19 and in housemates who have no complaints (yet). Research and expected outcomes Collecting saliva is simple and less annoying than a nose and throat swab. You can do it yourself. That is why it is being investigated whether the virus is equally detectable in saliva. Because you can collect a larger volume of saliva, it is possible to find a low dose of virus earlier. This applies both before someone becomes ill or with mild complaints, and after the complaints have already disappeared. That is why housemates are also tested and monitored whether they get complaints. In saliva, antibodies against the virus can also be measured. It is therefore examined whether blood tests can be replaced by saliva tests. Saliva may also contain other viruses, bacteria and fungi. It is being investigated what these may contribute to the infection.",2020,2021,Spaarne Gasthuis,385732.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04200,1.043E+13,Serologic surveillance of SARS-CoV-2 during the 2020 pandemic in exposed and unexposed healthcare workers in a tertiary care hospital in Amsterdam (S3 study),"Project description In the S3 study, three groups of hospital employees are followed within the Amsterdam UMC during the COVID pandemic. These are doctors and nurses in the COVID wards, doctors and nurses in the non-COVID wards and employees without direct patient contact. Periodically it is checked whether these employees have produced antibodies against SARS-CoV-2 in order to determine whether healthcare employees are infected more often and, if so, which employees are at greatest risk. Questionnaires are used to identify whether certain exposure risks in the workplace (eg in which department someone works, whether the correct protective measures are followed, whether colleagues have had complaints, etc.) are associated with a higher chance of infection. In addition, it is being investigated whether having antibodies against other coronaviruses that frequently cause a 'common' cold in the Netherlands has an influence on the course (complaints, antibody response, etc.) of SARS-CoV-2. In the S3 study, three groups of hospital employees are followed within the Amsterdam UMC during the COVID pandemic. These are doctors and nurses in the COVID wards, doctors and nurses in the non-COVID wards and employees without direct patient contact. Periodically it is checked whether these employees have produced antibodies against SARS-CoV-2 in order to determine whether healthcare employees are infected more often and, if so, which employees are at greatest risk. Questionnaires are used to identify whether certain exposure risks in the workplace (eg in which department someone works, whether the correct protective measures are followed, whether colleagues have had complaints, etc.) are associated with a higher chance of infection. In addition, it is being investigated whether having antibodies against other coronaviruses that frequently cause a 'common' cold in the Netherlands has an influence on the course (complaints, antibody response, etc.) of SARS-CoV-2.",2020,2021,Amsterdam UMC - location VUmc,66112.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies,Disease transmission dynamics,2020 +C04201,844001801,"Supporting family members of isolated, life-threatening ill patients with COVID-19 who have been admitted to intensive care","Project description At the time of the corona crisis, it is even more difficult to inform and support family members of isolated COVID-19 patients admitted to intensive care (IC) and isolated. Attention to loved ones is very important, especially in times of crisis. That is why ad hoc initiatives have emerged in various places to be able to offer good information and support to loved ones. Research We evaluate these initiatives to gain insight into how best to support loved ones in future, similar situations. This is done by means of questionnaire research and in-depth interviews with family members, IC staff and care providers who provided the extra support. Expected results After discussion with experts, the results will be incorporated into a guide with practical advice. Expected impact Better support for family members in future, comparable situations, because the guide makes it more feasible to start up a good support initiative.",2020,2022,"Amsterdam UMC, location VUmc",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Health Systems Research,Health service delivery,2020 +C04202,1.043E+13,The COUNTER-COVID study: Oral imatinib to reverse pulmonary vascular leak and disease burden in COVID-19,"Project description One in five patients with COVID-19 develops serious lung damage, necessitating hospitalization or even an Intensive Care Unit. This lung damage is caused, among other things, by leakage in the smallest blood vessels of the lung, whereby fluid escapes from the bloodstream and fills the alveoli. The fluid in the alveoli seriously impedes oxygen uptake and causes life-threatening oxygen deficiency. There are currently no medications to prevent leakage of small blood vessels. Research and expected outcomes Previous research in the laboratory has shown that the existing drug imatinib prevents blood vessel leakage. This protective effect of imatinib on the blood vessel wall can therefore potentially be used in patients with COVID-19. The COUNTER-COVID study tests whether patients treated with imatinib recover faster than patients who receive standard care.",2020,2022,Amsterdam University Medical Center - location VUmcǨǨ Ǩ,546881.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C04203,1.043E+13,The development of a COVID-19 scoring system for effective and safe triage of patients in the primary care setting.,"Project description With the recently started corona emergency centers, where patients suspected of having COVID-19 are assessed by a general practitioner, the entire primary care is separated into a 'corona-suspect' and a 'non-corona-suspect' side. When the primary health complaint is unlikely to be caused by infection with SARS-CoV-2, but the patient may still have symptoms of the COVID-19 clinical picture, he or she is referred to the 'corona-suspect' side. This precaution generates many unnecessary references to the corona emergency room, where patients are exposed to an environment with risk of contamination. There is a great need among general practitioners for an objective rule about deciding on which side to evaluate patients with possible COVID-19 symptoms. The purpose of this research is to develop a simple rule to support this decision. This must be immediately implementable at all GP practices and emergency centers.",2020,2021,Leiden University Medical Center,54910,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C04204,844001803,The impact of the COVID-19 pandemic on death and bereavement (the CO-LIVE project),Project description The COVID-19 epidemic is likely to continue for a long time. It is important to learn from the experiences now. The aim of the present study is to balance safe care and the needs of dying patients and their families Research Survivors and caregivers are asked about their experiences with end-of-life care for someone who died during the COVID-19 pandemic. This is done through online questionnaires and interviews. Expected results Understand what survivors and caregivers think of high-quality end-of-life care during the COVID-19 pandemic. Understand what hinders and facilitates grief counseling for family members during the COVID-19 pandemic. Early identification of complicated bereaved grief and long-term problems and burnout among caregivers. The results are translated into practice in the form of guidelines for high-quality and safe end-of-life care. Expected impact A better balance between safe care and the needs of dying patients and their families.,2020,2022,Erasmus Medical Center,,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Unspecified,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04205,1.043E+13,Therapeutic inhibition of excessive lung inflammation induced by anti-SARS-CoV-2 antibodies,"Project description In critically ill COVID-19 patients, pneumonia is associated with very strong inflammatory reactions, which can lead to multiple organ failure and eventual death. The current treatment options for the critically ill COVID-19 patients are unfortunately limited. Since the development and distribution of a vaccine will take one to two years, there is an urgent need for treatment for this category of most ill patients. Research and expected outcomes This study will investigate the underlying reason for these severe inflammatory reactions and will test which possible treatment options (drugs) can counteract these extreme inflammatory reactions. The findings indicate that critically ill COVID-19 patients produce a different kind of antibody against the virus, which in turn triggers the extreme inflammatory response. This could explain why this group of patients deteriorates so much after about a week and a half.",2020,2021,Amsterdam University Medical Center - location AMC,332902.86,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis,2020 +C04206,1.043E+13,Towards Evidence-based Social Distancing Policy: Tracking Behavioral Responses to Pandemic Mitigation Measures and Implementation Strategies,"Project description There is currently no vaccine against the corona virus. The spread can be limited by keeping a distance from each other. The government offers guidelines, but are they also complied with? Do people keep their distance? Do they wear masks? Method A method is being developed to automatically measure compliance with guidelines. This allows behavioral changes to be monitored quickly and efficiently. Camera images and artificial intelligence are used for this. The method can be applied anywhere where there are cameras. Questionnaires and media analysis are also used to chart what citizens think of the guidelines. What are the benefits? The method shows whether people succeed in adhering to the guidelines and what they think of it. It signals changes well before they are reflected in contamination figures. This can help develop and assess policy, both in the current corona crisis and in future pandemics.",2020,2022,Netherlands Institute for the Study of Crime and Law Enforcement,548522.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C04207,1.043E+13,TRACE II: Outcome in patients undergoing postponed elective surgery during the COVID-19 pandemic,"Project description During the peak of the corona crisis in the Netherlands (March - May 2020), many planned operations were postponed. Many appointments with general practitioners and medical specialists have also been postponed, which means that patients may have been diagnosed with surgery later than normal. This can cause delays in scheduling an operation. This project investigates whether postponing surgery has consequences for the health and recovery of patients. In eight different hospitals, patients are asked to fill in questionnaires around their surgery and medical information is collected about their recovery after surgery. These data are compared to a control group of a large nationwide surgical patient survey conducted between 2016 and 2019 (TRACE I). The results of this research can help plan operative care in the future during a crisis situation.",2020,2022,Maastricht University Medical Center+,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04208,1.043E+13,Understanding the two faces of the COVID-19 immune response to predict clinical course and define strategies for early and late phase intervention,"Project description The immune system plays a striking double role in COVID-19. An effective immune response ensures that the virus is attacked and cleared away, but if that does not work properly, a hyper-activation of the immune system appears to arise, which can lead to serious problems. It is unclear what exactly goes wrong in the immune system in patients with a severe course and how they can best be treated. The use of immunosuppressive medications is one of the possible strategies. Research and expected outcomes In this study, a collaboration of the UMCU, RIVM and VUmc, a model of the underlying immune response in different phases of COVID is developed by measuring functional cellular defense and circulating protein profiles of patients of different ages and with a variation in disease severity. -19. In addition, predictive biomarkers will be identified and validated that provide insight into optimal timing for specific treatments.",2020,2022,University Medical Center Utrecht,549034.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C04209,114025007,Use of patient-relevant human lung epithelial cell models to study acute and long-term effects of COVID-19,"Project description The lung epithelium lines the airways and alveoli, and is the main cell type infected by SARS-COV-2, the virus that causes COVID-19. Mapping and understanding the lung epithelial response to SARS-CoV-2 infection is needed to better understand the short and long-term effects of the infection and the severity of COVID-19. In this project, we use our non-animal culture models for this. We will investigate how the epithelium obtained from different locations (from nose to alveoli) responds to infection with SARS-CoV-2. It also compares the epithelium response to SARS-CoV-2 with that to other coronaviruses to investigate what makes this virus so special. Furthermore, epithelial cells and immune cells from COVID-19 patients are compared with those from healthy persons.",2020,2022,Leiden University Medical Center,548404.84,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C04210,1.043E+13,"WikiPathways as a platform for COVID-19 pathway models. Identification of underlying mechanisms explaining differences in host immune response, disease severity and detection of mechanisms for targeted (drug) treatment","Project description WikiPathways is a world-renowned and established knowledge platform, founded and maintained by Maastricht University. The platform makes molecular pathway models accessible to researchers, keeps its pathway collection up-to-date and supports the process of drug development for the different phases of COVID-19. Research The research has three aspects to help fight COVID-19 and future outbreaks: Extension of WikiPathways as a source for COVID-19 pathway models. This is done by sharing models and information and collaborating with all COVID-19 studies. Improvement of software to better describe virus-human interactions within relevant COVID-19 molecular processes so that computers can use them. The development of analysis procedures using the constant influx of knowledge, experiments and clinical data.",2020,2022,Maastricht University Medical Center+ǨǨ Ǩ,470997.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,Data Management and Data Sharing,,,Netherlands,Netherlands,Health Systems Research,Health information systems,2020 +C04303,173142,COVID-19 Associated Outcomes of Critical Illness in Patients with Frailty,Not provided,2020,2021,University of Alberta,29256.2,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C04304,unknown,Improving Outcomes in Individuals with COVID-19 with Renin-Angiotensin System Inhibition: The COVID-RASi Trial,"Cardiovascular disease is not only the #1 killer chronically, but is also the #1 killer in COVID-19. Elderly patients with previous heart attack or stroke, or hypertension or diabetes, have high risk of getting infected. Surprisingly they also suffer 3 to 5 times the chance of dying compared to other infected patients. A clue may lie in a group of commonly used medicines, called renin-angiotensin system (RAS) inhibitors, including ACE inhibitors and angiotensin receptor blocks or ARBs, usually extremely protective for our cardiovascular patients. But they have come under attack because they are suspected to increase the levels of ACE2 in the body, also part of RAS, which is the receptor for the virus, or the doorway for virus to enter our body. So are these agents safe or dangerous? This has become a major source of fear for both patients and physicians alike, and a raging controversy. To answer this question, we analyzed data from Wuhan, and found that these agents actually to be extremely protective. This finding was also replicated in another study examining patients in Europe and America. However, these data looked backwards at events past, which can be fraught with hidden biases. Therefore, the world desperately needs a proper forward-looking trial to evaluate these agents in COVID-19. Together with our Canadian and international partners experienced in COVID-19 research, we are starting this large trial to evaluate whether adding ACE inhibitors, or ARB's, compared to no added treatment in high risk COVID-19 patients, can decrease the chance of dying, requiring ventilators or ICU. A positive trial showing benefit will potentially save many lives in the world, using a very simple and cheap set of medications. Even if we found the medications to be safe, it will be very reassuring for millions of patients. We want to answer this question with urgency to benefit Canadians and cardiovascular patients worldwide in this COVID-19 era.",2020,2020,Ottawa Heart Institute Research Corporation (Ontario) Medicine,893774.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C04305,109547,"Portable, Low-cost Hardware for De-centralized COVID-19 Diagnostics for Canada, Colombia and Ecuador","Here we propose to develop and demonstrate the hardware and molecular tools needed for high-capacity de-centralized COVID-19 diagnostics in Canada, Colombia and Ecuador. We will do this by adapting our portable plate reader, called PLUM, for distributed deployment of two key diagnostic modalities using our patient validated tests. 1) A rapid molecular SARS-CoV-2 diagnostic (RT-LAMP, 15 min) to prevent a resurgence of infection as our communities begin to reduce lockdown restrictions. 2) Serological testing to determine population antibody-levels and allow for strategic use of precious, future vaccine stocks. To bring these diagnostics assays (96 or 384 well plate) out of the laboratory setting and to the point-of-need, we will adapt the PLUM reader to provide the high-temperature incubation (65 C) needed for RT-LAMP. PLUM will also be augmented with purpose-built software and training materials to enable the use of diagnostics by users in the field (e.g. health care workers). This will include automated software for guidance on sample collection, running the assays, data analysis and secure data sharing to public health networks. The RT-LAMP assay, which has already been extensively tested with SARS-CoV-2 patient samples, will be augmented with new safeguard features to prevent false negative results and adapted to allow for RNA extraction-free use. The COVID-19 serological assay has also already been extensively validated with SARS-CoV-2 patient samples and here will be optimized for use in PLUM. Implementation and testing of this de-centralized diagnostic capacity will be performed at small businesses in Canada, and with hospital workers and remote populations in Colombia and Ecuador. Taken together, this proposed project combines a strong technical solutions with patient trials outside of conventional laboratory settings and will enable the development of the crucial de-centralized COVID-19 testing capacity needed for recovery from the pandemic.",2020,2020,University of Toronto Biomolecular Sciences,336319.76,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada | Colombia | Ecuador,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04306,109555,"An international multi-site, randomized controlled trial of a brief eHealth intervention to increase COVID-19 knowledge and protective behaviors, and reduce pandemic stress among diverse LGBT+ people","The extreme global impact and still uncertain path of COVID-19 demands collaboration among researchers and communities in high- (HIC) and low-income countries (LMIC) to effectively halt the pandemic. Currently, public health recommended behavioural measures, such as handwashing and physical distancing, are the only effective approach to prevent COVID-19. However, COVID-19 exerts a disproportionate impact on marginalized populations. Existing disparities in health and its social determinants increase vulnerability to COVID-19, and creates barriers to adopting public health measures, which deepen resulting inequities. LGBT+ populations, including intersections with other forms of marginalization by race/ethnicity, gender, age and HIV status, experience extensive health disparities, and challenges due to unstable housing, employment, healthcare discrimination, and violence. Yet, there are no coordinated pandemic responses to address the expectable excess burden of COVID-19 among diverse LGBT+ people in Canada or LMIC. Community-engaged approaches are essential to bridging mistrust and loss of confidence in public health communications on the part of vulnerable communities, fueled by existing inequities. To address substantial gaps in the pandemic response, we will rapidly mobilize our existing global research team to adapt, test, and disseminate a community-engaged, brief, online peer-delivered intervention (#SafeHandsSafeHearts) with diverse LGBT+ populations to reduce risk in the pandemic. We will test the intervention's effectiveness in increasing COVID-19 knowledge and protective behaviours, and reducing psychological distress among cisgender gay/bisexual men, cisgender lesbian/bisexual women, and transgender people in Canada, India, and Thailand. In addition to immediate impact in slowing the spread of COVID-19, results will inform health system and public health responses to support engagement of LGBT+ and other marginalized populations in the pandemic response.",2020,2020,University of Toronto Social Work,374638.2,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas | South-East Asia,,,,Canada,Canada | India | Thailand,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2020 +C04307,172732,COVID-19 Ring-based Prevention trial with Lopinavir/ritonavir (CORIPREV-LR),"COVID-19 is a global pandemic that has taken a heavy toll on Canada. The prevention of new cases is critical, but vaccines are not likely to be ready for study for 1+ years. CORIPREV-LR is a randomized controlled trial of a prevention strategy called post-exposure prophylaxis (PEP) against COVID-19, in high-risk exposed contacts of confirmed cases. PEP is a well-established approach to the prevention of infectious diseases, in which people who were recently exposed to the virus take a short course of medication to prevent infection. Our primary objective is to find out whether taking an oral medication called lopinavir/ritonavir (LPV/r) for 14 days as PEP protects people from getting COVID-19, if taken shortly after they are exposed to a confirmed case. We will use an innovative 'ring'-based study design, in which we define a 'ring' of exposed contacts around confirmed COVID-19 cases, and then randomize these rings to either the study drug or control (no study drug) condition. This ring design was a key part of the successful eradication of smallpox, and the evaluation of a vaccine used for Ebola. The study drug LPV/r is an anti-HIV medication already marketed in Canada as KaletraTM. Molecular, animal model and early clinical data suggest it to have antiviral activity against SARS-CoV-2, the virus that causes COVID-19. It has a well-established safety profile, based on extensive global experience using it for HIV treatment and prevention for over 20 years. If our trial shows it to be effective, it could be immediately put to use in Canada and around the world, constituting a breakthrough in pandemic control. Our study team includes Canadian experts on the frontlines of SARS, MERS, H1N1, Ebola, and HIV, are our connections with clinical trial networks both in Canada and internationally will allow rapid data-sharing and dissemination of results.",2020,2020,Unity Health Toronto,621649.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments | Therapeutic trial design,2020 +C04308,unknown,PURE SARS-CoV-2: A Prospective Urban Rural Epidemiology (PURE) Substudy,"In this study, we aim to find answers to 2 important unknowns about COVID-19: 1) We do not know if there are factors that increase the risk of people getting infected by COVID-19 or that protect against infection; 2) What are the long-term health effects of getting infected by COVID-19. Specifically, we want to know whether having had COVID-19 infection - even if symptoms were not severe - can lead to long-term lung damage and other complications, like pneumonia, heart attacks, heart failure, stroke. We will find these answers by studying 40,000 adults from 30 communities in 13 high-, middle- and low-income countries. These individuals have already agreed to participate in an ongoing study called the PURE study. They have already provided us with a lot of information about their health, behaviours and medications and we have performed physical measurements and tested their lung function. In this study, we propose testing the blood of these individuals for signs of COVID-19 infection. We can then see if people who had COVID-19 exhibited particular characteristics, such as smoking, alcohol use or low physical activity that increased their risk of getting COVID-19. Because people with bad COVID-19 infection often get damaged lungs, we will test the lung function of participants to see if silent or mild infection lead to injured lungs as well. Finally, we will follow the study participants up for 3 years more to see whether people who had COVID-19 infection develop late complications such as lung disease, heart or circulatory problems more often than people who did not get COVID-19. This unique study will provide information to guide us as individuals and as communities on how best to avoid getting COVID-19 and on potential harmful long-term consequences of infection that we need to prepare for. [Also see https://www.thelancet.com/article/S0140-6736(17)32252-3/fulltext and http://www2.phri.ca/pure/#:~:text=Participating%20Countries%20and%20Territories%3A%20Argentina,Arab%20Emirates%2C%20Uruguay%2C%20Zimbabwe for a list of participating countries in the PURE study]",2020,2020,McMaster University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas | Eastern Mediterranean | Europe | South-East Asia | Western Pacific,,,,Canada,Argentina | Bangladesh | Brazil | Canada | Chile | China | Colombia | Ecuador | India | Iran | Kazakhstan | Kyrgyzstan | Malaysia | Pakistan | Palestine | Peru | Philippines | Poland | Russia | Saudi Arabia | South Africa | Sweden | Tanzania | Turkey | United Arab Emirates | Uruguay | Zimbabwe,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C04309,"172711, 175545, 175556",Towards a comprehensive understanding of adaptive immunity to SARS-CoV-2 [Added supplement: COVID-19 Variant Supplement; COVID-19 Variant Network],"The vast majority of people who get COVID19 fully recover from infection. This means that their immune system has successfully eliminated the virus. After we recover from a virus infection, the immune system leaves behind white blood cells, called memory cells, that can remember the previous infection and prevent that infection from recurring upon re-exposure. This is the basis of how vaccines work. After we recover from infection, two kinds of white blood cells persist, T cells and B cells. T cells and B cells have molecules on their surface that allow them to recognize the specific virus they were first exposed to. B cells give rise to antibody producing cells, while T cells can eliminate infected cells. Some antibodies can bind the virus in such a way that they fully block the virus from entering the cell. These are called neutralizing antibodies and these are ideal to fully protect us from being infected again. However, in some infections, weak antibodies, instead of neutralizing the virus, can actually make things worse by promoting uptake of the virus into cells or by overstimulating certain cells of the immune system. Therefore, there is a pressing need to understand the details of the immune response in COVID19 patients. We need to understand what parts of the virus are recognized when we have an immune response associated with a good outcome and what if any aspects of T and B cell responses are associated with a bad outcome. By studying the immune response in asymptomatic, mild and severe cases in depth, we hope to determine the correlates of a good immune response and use this information to design vaccines and to monitor people for the correct immune responses. For some infections T cell and B cell responses last a lifetime, whereas for other infections they do not last as long. Our study will develop the tools we need to follow how long the immune response to COVID19 infection lasts and to help with evaluating the level of protection in the population.",2020,2022,University of Toronto Immunology,1097328,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C04310,unknown,Household transmission of SARS-CoV-2 in a well-characterized African cohort,"COVID-19 poses unique risks to communities in resource-limited regions of sub-Saharan Africa (SSA). So far, little is known about the incidence, risk factors or outcomes of COVID-19 in SSA, or how these might differ from other areas with different resources, household structures and cultural practices. Elsewhere, COVID-19 is strongly associated with increasing age, male sex, and medical problems. Unexpectedly, children rarely get severe COVD-19 and do not appear to major contributors to spreading the infection, unlike with other respiratory viruses. Detailed household transmission studies of SARS-CoV-2 have the potential to reveal invaluable insights into how SARS-CoV-2 is transmitted, and have been recommended by the World Health Organization. We will take advantage of a CIHR-funded prospective cohort of 210 households in Nairobi, Kenya, which began in early 2019 and was designed to study the transmission of other viruses, to determine the local patterns of SARS-CoV-2 transmission among children and adults. Serum samples were collected from women (half of whom have HIV) who were enrolled during pregnancy, their newborn infants, and all other household members (895 people total), before the pandemic began. Blood collected every 3 months will be tested by different methods to detect SARS-CoV-2 antibodies to see how often infection occurred. Weekly saliva, urine and stool samples are also collected from 100 of the households, which will be tested for SARS-CoV-2 to see how the virus is spread. Because we have all the approvals to do the work and the cohort is already being followed, this study is a highly efficient way to study SARS-CoV-2 transmission in an African setting, where age-structure, household and community practices, and rates of HIV and other co-infections differ from other parts of the world. Thus, this work will provide timely insight into the global COVID-19 pandemic, and guide public health interventions in resource-limited settings.",2020,2020,University of British Columbia Pediatrics,342482.6,Human Populations,Black,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Kenya,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C04311,unknown,"Kukaa Salama (Staying Safe): A Pre-Post Trial of a WhatsApp Social Group for Increasing COVID-19 Prevention Practices with Urban Refugee and Displaced Youth in Kampala, Uganda","THE ISSUE: Poverty, overcrowded living conditions, and poor sanitation increase COVID-19 risks in humanitarian settings while limiting the ability to practice prevention strategies (e.g. physical distancing, hand washing). There is an urgent need for tailored COVID-19 responses with refugee/displaced persons. We address knowledge gaps regarding COVID-19 prevention in humanitarian contexts. We focus on urban refugee/displaced youth in Uganda, where 1.4 million refugees are hosted-Sub-Saharan Africa's largest refugee hosting nation and the 3rd largest globally. Our study is located in Kampala, Uganda that hosts 90,000 urban refugee/displaced persons living in informal settlements. Adolescents and youth comprise half of the world's 70.8 million refugee/displaced persons yet are understudied in pandemics. OUR IDEA: We will develop and evaluate the effectiveness of a WhatsApp social group intervention in increasing COVID-19 prevention practices (hand and respiratory hygiene, physical distancing) among our existing CIHR Project Grant cohort of urban refugee/displaced youth aged 16-24 living in informal settlements in Kampala. Our project involves: 1) qualitative phone interviews with refugee/displaced youth (n=24) and key informants (n=6) to understand barriers and facilitators to COVID-19 prevention, following the RANAS (risk, attitude, norms, ability, self-regulation) approach to behaviour change; 2) integration of the qualitative findings to develop Kukaa Salama (Staying Safe), a 16-week COVID-19 prevention intervention (weekly SMS and moderated WhatsApp discussions); 3) conducting a single arm, pre-test/post-test trial to test the effectiveness of Kukaa Salama in improving COVID-19 prevention with refugee/displaced youth aged 16-24 (n=340); 4) knowledge mobilization, including a think tank to produce a refugee policy analysis. Findings will advance the COVID-19 global response with new knowledge of mHealth approaches for COVID-19 prevention in humanitarian contexts.",2020,2020,University of Toronto,224386.96,Human Populations,Black,Unspecified,Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Uganda,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions | Community engagement,2020 +C04312,172756,Pandemic Planning for Primary Care: Lessons from Four Provinces,"Family physicians (FP) play an important role in pandemic response and recovery. However, existing pandemic plans do not adequately incorporate FP. What are the roles of FP during a pandemic? What facilitates and hinders FP from fulfilling these roles? The goal of the project is to inform the development of pandemic plans for FP by examining experiences in four regions in Canada: Newfoundland and Labrador, Nova Scotia, Ontario, and British Columbia. The project is a multiple case study of regions in four provinces. Each case consists of a two-part mixed-methods design consisting of: 1) chronology of FP roles in the COVID19 pandemic response and 2) qualitative interviews with FP. In each province, we will create the chronology through a document review (supplemented, as needed, by key informant interviews) to describe key milestones in COVID19 pandemic and FP roles and responsibilities at each stage of the pandemic. Using the chronology as common frame of reference, we will conduct semi-structured qualitative interviews with FP who work in each region. In the interview, for each pandemic stage, we will ask FP to describe the facilitators and barriers to performing the proposed, actual and potential roles FP, and the influence of their gender on roles, facilitators and barriers. Results will provide government ministries, public health units, other health organizations, and FP evidence and tools (such as checklists) with which to respond to a second COVID19 wave and plan for future pandemics.",2020,2020,Western University,244234.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C04313,109551,Assessing the impact of COVID-19 response on malaria control and malaria burden in rural Tanzania,"The World Health Organization has warned that deaths from malaria could double across sub-Saharan Africa this year if malaria control programs are disrupted by COVID-19. Currently, 94% of all malaria deaths occur in sub-Saharan Africa, with children and pregnant women amongst the most vulnerable groups. Given recent estimates that predict a return to mortality levels last seen 20 years ago, it is critical that countries can maintain the delivery of insecticide-treated nets and access to antimalarial medicines in the face of the COVID-19 pandemic. To better understand the COVID-19 response in Tanzania and its impacts on malaria control and burden, we will collect information on COVID-19 and malaria prevention practices, malaria care-seeking behaviours and health system impacts in a rural district where a large-scale malaria vector control trial is underway. Data will be collected using a mixed methods approach through (1) repeated cross-sectional surveys with 4200 households in January 2020, July 2020 and January 2021, (2) focus group discussions with women and men in randomly selected communities, and (3) key informant interviews with multiple health systems stakeholders. We will apply a sex and gender based analysis plus (SGBA+) approach to identify vulnerable population sub-groups. We will conduct spatial and trend analyses of survey data and thematic analysis of qualitative data to characterize individual and health systems level responses to COVID-19 and estimate gaps in malaria intervention coverage. We will use simulation models to estimate the potential impacts of changes in malaria control on the burden of malaria disease and death using the 'OpenMalaria' simulator of malaria epidemiology and control. Our results will inform strategies to tailor malaria control strategies in the context of COVID-19 in Tanzania to ultimately prevent a resurgence in malaria cases and deaths while ensuring effective pandemic response.",2020,2020,University of Ottawa Epidemiology and Public Health,103072.72,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas,Gender,,,Canada,Canada | Tanzania,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04314,109554,"Validation of rapid, molecular testing for COVID-19 and integration with TB diagnostics","We are living in a world severely disrupted by the COVID-19 pandemic, but it is critical we do not neglect other diseases that persist outside of the global spotlight. Losing progress against the worldwide tuberculosis (TB) epidemic would mean adding to the 1.5 million TB-related deaths reported each year, but it is not inevitable. The symptoms for COVID-19 and TB are similar, with fever and cough both frequently observed. As such, integrating COVID-19 and TB testing is an opportunity to improve the quality of patient care by taking advantage of already-existing infrastructure. One example is GeneXpert, a diagnostic platform proven to be effective in low- and middle-income countries (LMICs) for TB diagnosis. The TB test, Xpert MTB/RIF, rapidly detects TB with high accuracy. Recently, a COVID-19 test, Xpress SARS-CoV-2, received FDA emergency use authorization for use on the GeneXpert platform. This is a promising development, particularly for LMICs with extensive GeneXpert networks already in place, but the test's diagnostic accuracy is unknown. We propose a validation study of Xpress SARS-CoV-2 to evaluate its diagnostic accuracy in Peru, a middle-income country already using GeneXpert. After obtaining an estimate of the test's performance, we will assess the feasibility of integrating testing for COVID-19 and TB on the GeneXpert platform. Namely, we will collect one sputum sample from individuals presenting with clinical symptoms typical to COVID-19 and TB, and test them using Xpress SARS-CoV-2 and Xpert MTB/RIF, respectively. We expect that the amount of COVID-19 and TB detected will be similar to what we would have detected with complete but time-consuming diagnostic work-ups for each disease. Testing for two diseases with common symptoms in one clinical interaction will be convenient for patients and healthcare workers. Having rapidly available diagnostic data will facilitate a more timely response for patient care and, ultimately, population-level planning.",2020,2020,Research Institute of the McGill University Health Centre,320324.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04315,172629,HOST RESPONSE MEDIATORS IN CORONAVIRUS (COVID-19) INFECTION - IS THERE A PROTECTIVE EFFECT OF ARBs ON OUTCOMES OF CORONAVIRUS INFECTION? (ARBs CORONA II),"As the COVID-19 pandemic continues to spread globally, the World Health Organization (WHO) and others are actively conducting clinical trials for anti-virals to combat this disease. However, many of the severe complications of COVID-19 are caused by the host's response to viral infection. We have a unique opportunity to complement these ongoing studies with our clinical trial to test how modulating the host response can improve outcomes for hospitalized COVID-19 patients. We plan to re-purpose a class of drugs called angiotensin II receptor blockers (ARBs), which are normally used to treat high blood pressure and other cardiovascular diseases. ARBs have been shown to prevent lung injury in influenza (the flu), which is caused by a virus that uses similar mechanisms as SARS-CoV-2 (the virus that causes COVID-19) to enter human cells. We will recruit 1,732 patients from multiple sites throughout Canada and randomize them to be treated with either Losartan (a commonly prescribed ARB with an excellent safety profile), or to continue under usual care. We will evaluate whether patients who receive Losartan have better outcomes, such as decreased mortality and organ dysfunction, than those who receive usual care. At the same time, we will collect blood samples from these patients to determine whether there are certain molecular ""markers"" that can predict mortality and their response to Losartan. This study will provide guidance on whether Losartan can be used to limit organ dysfunction and mortality in hospitalized COVID-19 patients, ultimately resulting in better care and outcomes for patients during this global pandemic.",2020,2020,University of British Columbia Medicine,2626971.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C04316,"172626, 175553",SARS-CoV2 therapeutic discovery through genetic screens and repurposing drugs that target essential virus-host interactions. [Added supplement: COVID-19 Variant Supplement],"The worldwide pandemic of COVID19 caused by the virus SARS-CoV2 has caused over 270,000 human lives and worldwide economic collapse. While public health measures such as social distancing and shutdown of non-essential businesses have been effective at slowing virus spread, restarting society and economies in Canada and around the world will require intensive testing and contract tracing, and ultimately effective treatments and vaccines. In this proposal our goal is identify existing therapeutics that can be re-purposed to treat SARS-CoV2 infections. During an infection viruses must hijack host machinery and regulatory pathways in order to reproduce, and some of the pathways used by viruses are the same ones that are dysregulated during human diseases such as metabolic diseases and cancer. Thus, it is likely that therapeutics designed to treat metabolic diseases and cancer also inhibit SARS-CoV2 infections. However, the specific machinery and regulatory pathways used by SARS-CoV2 remain unknown and the potential inhibitors undiscovered. Our strategy is to identify the host machinery and regulatory pathways the virus needs to grow, and then test drugs that target these proteins to see if they inhibit SARS-CoV. Finally, many different types of coronaviruses likely also use the same host machinery and regulatory pathways so the inhibitors we discover might also be effective against other coronaviruses so could help society prepare for future coronavirus outbreaks and avoid future pandemics.",2020,2022,"University of Saskatchewan Biochemistry, Microbiology & Immunology",370167.14,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C04317,unknown,Protecting healthcare workers from COVID-19: A comparative contextualized analysis,"This research focuses on measures to protect healthcare workers (HCWs) who are at substantially increased risk because of their direct contact with COVID-19 infected patients - and with considerable variation being experienced internationally in different settings. Although there is general agreement on many aspects of policy to protect HCWs, approaches have varied widely with very limited availability of contextualized evidence to guide local decisions. Often differences have been due to availability of specific personal protective equipment (PPE-e.g. N95 respirators, masks, gloves, gowns); sometimes differences have been due to operational necessities (e.g. whether exposed HCWs can continue to work while wearing PPE); sometimes variations in policies relate to availability of COVID-19 test kits or related reagents (e.g. criteria for testing or whether pre-return-to-work testing is implemented); approaches to exposure monitoring and contact tracing for HCWs also vary widely. It is critically important for policymakers to understand consequences of these variations, as well as scrutinize their scientific and contextual rationales. This proposal asks ""What works to protect HCWs, in what contexts, using what mechanism, to achieve what outcome?"" By building on a strong track record of interdisciplinary research in exactly this field, with well-established international networks with expertise in infection control and occupational health, and a long-history of relationship-building to facilitate this research, this team is extremely well-positioned to conduct this highly relevant research and provide world leadership in this area. It will be conducted through in-depth case studies conducted in Vancouver, Canada and Gauteng, South Africa as well an international cross-country comparative analysis based on surveys and experiences in protecting healthcare workers and a case-control study of workers with COVID-19 infection versus other workers in their same facilities.",2020,2020,University of British Columbia School of Population and Public Health,311794.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | South Africa,Epidemiological studies | Infection prevention and control,"Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +C04318,173056,"Trust, Acceptance and Sufficiency: Law as a Barrier to, and Enabler of, Routine and Responsive Immunization including COVID-19A","Primary disease prevention through immunization is a global public health priority with clear economic and health and well-being benefits. However, there is growing recognition in Canada that vaccine uptake rates are not where they need to be for adequate control of vaccine preventable diseases. Importantly, these rates can be further eroded by unanticipated disruptive events such as a pandemic for which there is yet no vaccine (e.g., COVID-19). While control of COVID-19 will be more feasible once vaccine(s) become available, this will not be a simple decision federally or for the provinces and territories as it is highly probable that different types of COVID-19 vaccines will be available in Canada which differ as to safety and efficacy parameters, age targets, etc. While practice/program decisions need to be based on sound scientific evidence, legal considerations relevant to program design and delivery will frequently arise. For example, consider cases in which there are differences between manufacturer license recommendations and effective case- and conditions-sensitive use by and within programs. This project is a first step in gaining a better understanding of immunization, both routine and responsive i.e. in a pandemic, as a 'regulated space' . Laws may both help and may also hinder. The project will generate significant new insights into the content and scope of immunization governance frameworks ( laws and regulations) that exist across Canada, offering observations about their potential as barriers to, and enablers of, public health goals, with special attention to two issues that COVID-19 has already highlighted as problematic, namely the issues of mandates and vaccine injury compensation. The ultimate aim is to assist in identifying what might be done for Canada to perform better in this setting, taking into account its actions in response to COVID-19.",2020,2021,Dalhousie University,182955.56,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Health Canada,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Vaccine/Therapeutic/ treatment hesitancy | Health leadership and governance,2020 +C04590,AH/V006991/1,COVID-19: Using multisensory culture boxes to promote public health guidance and to support the wellbeing of people with dementia in care homes.,"This study addresses two urgent challenges. Firstly, providing COVID-19 (CV-19) information for those with cognitive impairment, specifically people with dementia in care homes 1 . Secondly, alleviating social isolation and loneliness in care homes 2, 3 by providing creative activities that support wellbeing for people with dementia 4 , especially, in the context of long-term CV-19 lockdown and restrictions 5, 6. This project will produce, distribute and evaluate CV-19 culture boxes incorporating pandemic guidance with creative activities to support health and wellbeing and alleviate social isolation and loneliness for people with dementia in care homes. The team will work with the Geller Institute of Ageing and Memory (IAM), stakeholders including people with dementia, staff and family carers and allied professionals, including BAME representatives, to co-design culture boxes with artists. These will be delivered weekly for 3 months (then repeated, updated, for 12 months). Each will contain multisensory materials (subject to health and safety guidance) suitable for diverse populations that: provide information about CV-19 transmission and prevention, with creative resources including music and art activities that are simple to implement and offer stimulation and enrichment. The weekly delivery aims to reinforce public health messaging and to mimic regular activities in care homes. The National Activity Providers Association (NAPA) will support distribution via their network of 3000 members. The project will be evaluated using Participatory Action Research (PAR) 7 . All resources will be archived via the NAPA website ensuring that they are widely available. Dissemination includes an art exhibition, conferences, educational presentations, and a peer-reviewed paper.",2020,2021,University of West London,431038.02,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C04591,AH/V006940/1,Scottish Public Libraries and their role in community cohesion and resilience during lockdown,"In 'normal' times public libraries are crucial community hubs but have, like other public spaces, been closed during the pandemic lockdown. In recent years, public libraries in Scotland have been strongly supported through Scottish Government initiatives (e.g. Public Library Improvement Fund) or through a national strategy for their enhancement (Ambition and Opportunity 2015-20) and are seen as highly trusted public spaces. They play a major role in supporting disadvantaged or socially-excluded members of the community (e.g. through supporting online benefit claims), aiding wellbeing (e.g. Macmillan Cancer centres) and developing literacy (e.g. Bookbug), supporting economic growth (e.g. co-working hubs). The lockdown means they have been compelled to adapt their offerings significantly and, often, creatively. Many have reported surges in the borrowing of e-books(e.g. Aberdeen), they have developed online book clubs (Glasgow et al), 3D printers creating PPE, or online storytelling sessions (Shetland). This research will examine how they have responded to the lockdown, reimagined services and explore the impact on both the services themselves and the end users. It will also seek to understand the difficulties such as those members of the community for whom online access is problematic or even impossible if unable to visit the library physically. The disparity in service provision (between those services in cultural or leisure trusts which have furloughed employees and those remaining in direct local authority control) will also be explored as in the context of the provision of statutory universal service. The research will inform policy and understanding of service governance and resilience",2020,2020,Robert Gordon University,19582.2,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C04592,MR/V015737/1,Urgent research and surveillance on COVID-19 using the new OpenSAFELY secure platform across 55 million patients' full linked primary care records,"Our group is delivering analyses across 27 million patients' full pseudonymised linked promary care NHS records, soon expanding to 55 million. This unprecdented scale is needed for rapid results during Covid-19.OpenSAFELY uses a new model for efficiency and privacy: we have built a secure analytics platform inside the data centres where GP records already reside, and linked to all relevant Covid-19 outcomes data.This is not a proposal for theoretical future delivery. All permissions are signed, all data has flowed, our first analyses are complete. We have achieved this with no external resource.We urgently need funds to sustain, accelerate and expand our work across diverse collaborative analyses. This application covers the platform, and three workstreams:1) Observational epidemiology to identify patients at higher risk of admission, ventilation and death from Covid-19, to inform management, seclusion advice, service planning, and underlying mechanisms (e.g. higher risk among BAME groups); to rapidly assess specific hypotheses arising around treatment/prevention including ACEi's, ARBs, ibuprofen, inhaled corticosteroids, antiocoagulants, and other treatments.2) Deliver innovative transmission models that combine disease-dynamics approaches with near-real-time hyperlocal data on prevalence and population at risk, to predict local spread and service need, and (for example) to design and evaluate exit strategies from lockdown.3) Measure and mitigate the indirect health impacts of Covid-19 on, for example, cancer presentations and referrals, cardiovascular management, vaccinations, etc, using research and observatory approaches to identify urgent necessary actions.",2020,2021,University of Oxford,657255,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Indirect health impacts,2020 +C04593,MR/V020498/1,Liverpool COVID-19 Drug Interactions,"One of the key developments in the fight against HIV/AIDS was the introduction of protease inhibitors in the mid-1990's. This class of drugs in combination with a nucleoside analogue backbone (highly active antiretroviral therapy, HAART) had a huge impact on viral suppression and patient outcome. However, an important trade off was that the protease inhibitors were either the perpetrator or victim of multiple drug-drug interactions. The Liverpool University Drug Interactions group recognised the problem and began developing a web-based resource (www.hiv-druginteractions.org) which over the last 20 years has become very much the gold standard and is now recommended in over 30 international guidelines and many national guidelines. The website has an associated App. In 2011, direct acting antivirals were introduced to treat Hepatitis C and the Liverpool team responded with a new website (www.hep-druginteractions.org) and App. In 2019, these websites had over 50,000 unique monthly visitors searching for > 4.5 million interactions. In response to the COVID-19 pandemic and to address the pressing need for prescribing support for studies and clinical situations where experimental COVID therapies are being used, we have developed a static drug interactions website (www.covid19-druginteractions.org) providing information on the likelihood of interactions between the experimental agents and commonly prescribed co-medications. We now have to move to develop a fully interactive and searchable website resource with an associated App. The website will be constantly updated and populated with the latest information on experimental therapies as it emerges with guidance given to clinicians for managing complex patients.",2020,2021,University of Liverpool,42683.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation | Health Systems Research",Adverse events associated with therapeutic administration | Health information systems,2020 +C04594,MR/V020544/1,Ensuring that COVID-19 trials consider ethnicity: the INCLUDE Ethnicity Framework for randomised trials,"Representation of the Black, Asian and minority ethnic (BAME) community in randomised trials is often poor. As we have seen in the news, the BAME community is disproportionately affected by COVID-19, which means it is essential that trials of treatments and vaccines for COVID-19 include people with BAME backgrounds. It is not clear that this is currently the case. Ongoing UK work looking at the design quality of global COVID-19 trials has found that just 1 of 9 published COVID-19 trials even mentions ethnicity. Of 1518 COVID-19 studies registered on ClinicalTrials.gov (the US registry of clinical trials), only six are currently collecting data on ethnicity. Considering ethnicity is not routine in trials. This project will complete a tool (called the INCLUDE Ethnicity Framework) that trial designers can use to make sure they think about factors that affect BAME involvement such as disease, culture, treatment being tested and trial information and procedures. It will also help people interpreting and reporting COVID-19 trials to make judgements about the applicability of trial results to BAME communities. We have already done some work without funding and this has included patient and public involvement from the BAME community. This proposal will use that feedback to finish the tool.",2020,2020,University of Aberdeen,9785.94,Human Populations,Asian | Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Research to inform ethical issues","Therapeutic trial design | Vaccine trial design and infrastructure | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2020 +C04595,MR/V027905/1,Understanding the impact of covid-19 on pregnant women and new parents: The Born in Bradford 2020 Families Study,"The COVID19 pandemic has dramatically changed how health care is delivered. Pregnant women have been identified as a vulnerable group to COVID19 and as a consequence, women have received much of their essential health care over the phone, and partners have not been able to attend maternity appointments including baby scans. After birth the usual social support offered by friends and family has been restricted due to social distancing. For women and their partners who are having a baby during this time there is concern that this could have an impact on their physical and mental wellbeing and the health and development of their babies. The recovery from the COVID19 pandemic needs research information on the health, social and economic impacts on vulnerable populations to be made available quickly to key policy and decision makers so that they can develop and implement policies and interventions to reduce potential longer term impacts of the COVID19 pandemic. The Born in Bradford (BiB) research programme (www.borninbradford.nhs.uk) is in a unique position to be able to provide such information on a key vulnerable population: pregnant women living in a highly deprived and ethnically diverse city. BiB have two ongoing birth cohort studies: Born in Bradford's Better Start (BiBBS) focussed on women living in ethnically diverse and deprived communities and BiB4All - a routine data linkage birth cohort study aiming to recruit all pregnant women booked to give birth at Bradford Teaching Hospitals NHS Foundation Trust. Participants give permission for follow-up via routine data from multiple agencies (e.g. GPs, maternity, health visiting, social care) and agree to be contacted for additional research projects with bespoke data collection. The aim of our study is to understand the experiences of being pregnant, giving birth and caring for a baby during the COVID19 pandemic. We will adapt the data collection within our birth cohorts to collect additional quantitative survey data and qualitative interview data at 4 time points during pregnancy and during the first year after birth. This will allow us to: a) understand how COVID19 has affected pregnant women (e.g., being identified as high risk by government, having changes to care or birth plans), and the short- and long-term impact these changes have had, for example on their expectations and experiences of care, their mental wellbeing, worries and concerns, birth outcomes; (b) understand how the crisis is affecting wider aspects of pregnancy and the transition to parenthood, for example peer-to-peer social support, support for breastfeeding and parenting, family relationships and livelihoods; (c) explore how these changes affect the partners of pregnant women during pregnancy and in the postnatal period; (d) inform practitioners, service providers and policy makers where intervention is needed to reduce the adverse effects of the health and well being of women and their babies in the short term and as part of recovery. We will combine the findings of our surveys and qualitative work and use expert groups of key stakeholders and local parents to co-produce recommendations for practice. This research will significantly contribute to understanding the impact of COVID19 on pregnant women and their partner's current and future health and the health and development of their children. It will also inform interventions to reduce the impacts of the pandemic. Bradford, like many other large UK cities, has high levels of deprivation and ethnic diversity, the findings from our study will therefore be scientifically valid and relevant to services and policy makers nationally. Our research team have connections to many other COVID19 research teams nationally and internationally as well as direct links into key national health organisations and policy makers. We will use these connections to ensure",2020,2021,Bradford Teaching Hospitals NHS Foundation Trust,415185.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2020 +C04596,MC_PC_20011,Community surveillance for SARS-CoV-2 and COVID-19 in the general and in high risk populations in Uganda and assessment of the wider impact of infection and of pandemic mitigation.,"This award is being made to allow the Unit to undertake rigorous community COVID-19 surveillance in high-risk and general populations in Uganda, in order to understand the wider impacts of pandemic spread and associated mitigation strategies. This will answer critical questions on transmission dynamics, burden and distribution of infection including identifying vulnerable groups.",2020,2021,MRC/UVRI and LSHTM Research Unit Uganda,1485050.58,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa | Europe,,,,Uganda,United Kingdom | Uganda,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures,2020 +C04597,MC_PC_20010,Enhancing the Unit Support of Uganda's Efforts to Contain COVID-19,"This award is being made to allow the Unit to support Uganda's efforts to contain COVID-19 through enhanced diagnostic support and testing capacity, re-deployment of Unit staff to the effort of sample collection and survey activities as well as clinical and procurement support.",2020,2022,MRC/UVRI and LSHTM Research Unit Uganda,1998529.92,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Unspecified,,,,Uganda,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research",Diagnostics | Health workforce,2020 +C04598,EP/V027263/1,SERVICE: Social and Emotional Resilience for the Vulnerable Impacted by the COVID-19 Emergency,"The social distancing imposed by COVID-19 is likely to effect unprecedented psychological impacts. This proposal responds to this need, applying our research on socio-technical resilience to: - Investigate the lived experience of the pandemic on older adults and their support networks. - Support the resilience of these networks in meeting ongoing emotional needs through the development of an adaptive digital platform which enables the recording, sharing, and analysing of wellbeing within a secure and privacy-respecting environment. We will also produce critical data and resources: - Multimethod public datasets on the social implications of COVID-19 and social distancing, the lived experience of social isolation, and the relationships between social support structures, digital engagement, and wellbeing over time. - Methods for software adaptivity in response to an individual's psychological requirements. Our work will address these research questions: 1. What are the benefits and shortcomings to socially distanced older people and their support networks of digitally recording, sharing and analysing psychological states? 2. How can a digital platform support the social support dynamics (requesting, offering and accepting) that were previously face-to-face? 3. What are the real-time relationships between social behaviours, loneliness, and emotion regulation for socially distanced older people? 4. How can we predict trends and trigger system adaptivity to encourage interpersonal engagement and thereby reduce the negative impacts of isolation? This project seeks to contribute to understanding of and response to the COVID-19 pandemic and its impacts due to social isolation, by digitally facilitating support/carer interactions and gathering critical data to assist personalized interventions.",2020,2021,Open University,626940,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C04599,EP/V026895/1,COVID-19: Reducing the Risk of Transmission on Londons transport vehicles,"We have much to learn about how COVID-19 has spread, however it is clear that being close to an infected person is a risk. The virus causing COVID-19, SARS-CoV-2, can be transmitted from one person to another through the air, by direct contact or via inanimate objects. The risk of transmission becomes higher the more people come into contact with each other as well as how long this contact lasts. Governments across the globe have enforced measures which aim to minimise person to person contact, including the transmission of saliva droplets carrying the virus. Public transport vehicles are spaces where the risk of transmission is high because a lot of people use them. London's underground and bus network runs millions of journeys daily and is running at a lower capacity during COVID-19 to minimise risk to passengers and staff. However, it is virtually impossible to maintain the 2 m distance recommended in the UK within the public transport system. This project will combine staff and passenger surveys, microbiological sampling, air flow computer simulations, passenger crowding and ventilation models and air quality measurements to better understand how the risk of transmission can be minimised on London's transport systems.",2020,2021,University College London,848852.25,Human Populations | Viruses | Environment,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2020 +C04600,MR/V027751/1,"Tracking the impact of Covid-19 on the mental health of children, young people and families; follow up of a national longitudinal probability sample","Children and young people's daily lives have been affected in many ways during the Covid-19 pandemic. Schools and colleges have closed to most children, while all have faced disruption to leisure activities and physical distancing from friends, family and community networks. The impact of the outbreak may be most severe for the groups who are already disadvantaged. Children and families needing help may have found it harder to access support during lockdown. Although there have been online surveys of children's mental health, we know that the most disadvantaged groups are less likely to take part in such studies, and we lack data on how children and young people were coping before lockdown. This means that we have a limited understanding of how different groups of children might be affected in the short and longer term. Information from a study that includes children from a wide range of backgrounds and is representative of the population is therefore needed in order to guide efforts to provide help for those affected, prevent longer term problems, and to better support children and families in the recovery from the pandemic, or during any future lockdowns or pandemic response. In this research, we will contact the parents, children and young people and families who took part in the national Mental Health of Children and Young People in England (MHCYP) survey 2017, and ask them to participate in three follow-up surveys, in July 2020, October 2020 and January 2021. The young people are now aged 5-22 years. The main aims of the research are: 1/ To track children's mental health and wellbeing over the course of the pandemic 2/ To identify groups of children whose mental health may have been most affected, 3/ To explore the factors which might increase the risk of problems, or protect against the development of mental health problems 4/ To report on changes in access to help and support for mental health concerns The surveys will ask about: child mental health and wellbeing, parent mental health, worries about coronavirus, impacts of coronavirus on the household (for example, employment and education), access to mental health help and support, and about the child or young person's daily life and activities. We will also invite some young people and families to take part in more detailed interviews about their experiences; the interview topics will depend partly on the findings of the surveys, and on the views and priorities of the young people, families, professionals and organisations working with us. Our team includes experts from the Office for National Statistics and NatCen Social Research who ran the previous national child mental health surveys, as well as from three universities (Cambridge, Exeter and Kings College London). We will be working closely with the Department for Health and Social Care, the Department for Education, and NHS England, as well as with charities and other groups working with children and families and running health, care and education services. We will also have an advisory panel of young people, parents, and professionals working in education, health and care. We will produce 'rapid reports' to help these groups and organisations plan and provide care and support for the children and families who need it most. For example, our findings may help in: identifying groups of children who might need additional support in any future lockdown or pandemic; or in planning services to meet specific needs such as increased levels of anxiety or trauma-related symptoms, and improved access to learning at home. We will work nationally and internationally with other researchers studying children's mental health and Covid-19, to help understand the mental health impacts on a global scale, and share our findings in academic journals and conferences. We will work with our advisory panel to develop blogs, videos",2020,2021,University of Cambridge,876925.23,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C04601,BB/V006738/1,Determining age dependent factors driving COVID-19 disease severity using experimental human paediatric and adult models of SARS-CoV-2 infection,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic of COVID-19. Our lack of understanding about the pathogenesis of SARS-CoV-2 in the human airways is an important barrier to developing effective treatment strategies for COVID-19. So far, we know that COVID-19 disease severity increases with age, with very few severe cases among children. In China, the case fatality ratio was 60-year olds, rising to 15% in those >80. This project will focus on two aspects of the host response of infection, studying how the cells that line the airway respond to the virus, and whether the recruited immune cells (focussing on the behaviour of neutrophils that are the first to respond to infection) the help reduce viral load or contribute to airway damage and the build-up of debris in the airways. We will use an experimental SARS-CoV-2 infection model of the airway epithelium from young children, adults and the elderly. Our objectives are to determine: 1) if the primary site of infection - the nasal epithelium - of the elderly exhibit increased viral replication and increased inflammatory response to SARS-CoV-2 infection compared to children. 2) the molecular mechanisms that govern age-determinants of COVID-19 disease severity using single-cell genomic analysis of cultured cells and comparing outputs to the same data from age-matched COVID-19 patients using scRNAseq. 3) whether the innate immune response to SARS-CoV2 infected airway epithelium exacerbates inflammation and contributes to the severity of illness in the elderly by measuring a) the intensity of immune cell (neutrophil) recruitment to the airway b) epithelial damage and c) neutrophil phenotype and function. It is important that we understand the reasons for these fundamental differences in responses in order to help determine what the most appropriate therapy is for COVID-19 disease in these age groups. There is much debate about the utility of novel and exsiting anti-virals as well as immune modulator therapies including NSAIDs and Tocilizumab. This project will rapidly deliver new understanding about the viral pathogenesis and the cause of these age-related disparties in disease outcomes. Not only will this help support the development of effective therapeutics in the short-term, underlining the relevance of this model for the preclinical evaluation of antiviral candidates, but it may also highlight important risk factors or protective mechanisms that could be used to develop early interventional or prophylaxtic therapies in the long-term.",2020,2021,University College London,490393.5,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C04602,BB/V011316/1,Identification of host cell components essential for the SARS-CoV-2 life cycle,"All viruses are dependent on host cell machinery for aspects of their lifecycle. We plan to identify non-essential host (human) cell components that are required for the life cycle of the SARS-CoV-2 virus. If we are able to identify them, these will provide critical intervention points for developing drugs that could prevent virus infection or hamper/stop viral replication. We will used a genetic approach, mutating each of the 20,000 genes in the genome and testing whether the virus is able to infect the cell, replicate and produce new infectious particles. The results will provide insights into molecular host-pathogen interactions at various steps of the virus life cycle including entrance, replication, biosynthesis, and release. Experimentally, we will try to identify mutant cells which do not support aspects of the viral life cycle. We will then seek to identify the underlying mutant gene(s) which are able provide this protection. Technically this will be achieved by killing/removing cells which have been successfully infected, allowing the ""resistant"" ones to survive. The initial stage of the project will be to establish sensitive and specific assays in human cell lines which can be successfully infected with SARS-CoV-2. Genetic screens would then be conducted with CRISPR libraries that target all the gene in the genome as well as a library specialised on ""drug targetable"" host genes. If hits are identified in a ""druggable"" library, the results could be rapidly translated. For instance by taking the corresponding drug and testing this on cells in culture. Hits identified by genome wide screens will take longer to translate, depending on the gene that is identified and prior work on the gene. The reporter cell lines we are developing to support this project as well as any targets we identify should support collaborative efforts with other laboratories and industrial partners, to translate these findings into host-directed therapies.",2020,2022,University of Cambridge,582998.73,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C04603,BB/V011308/1,COVID 19: LESSONS FROM FATAL CORONAVIRUS INFECTIONS IN COMPANION ANIMALS,"Companion animals are susceptible to coronaviruses, including SARS-CoV-2. This proposal addresses 3 important unmet needs: 1: We do not know precisely why certain individuals or ethnic groups are more susceptible to COVID-19, and whether this difference in susceptiblity has a genetic basis. 2: SARS-Cov2 is a novel virus, so we are poorly prepared to recognise or manage unforeseen chronic or late-presenting medical complications of COVID-19. 3: Dogs and cats may act as a reservoir for future zoonotic coronaviruses, but the responses of these species to coronaviruses are poorly understood. We hypothesise that transcriptomic and whole genome sequencing analysis in extreme responses to veterinary coronaviruses will reveal reveal new genetic susceptibilty loci and treatment targets relevant to COVID-19. These data will also increase preparedness for delayed COVID-19 complications and novel future zoonotic coronaviruses. CANINE RESPIRATORY CORONAVIRUS (CRCoV) is a highly contagious respiratory beta-coronavirus sharing many parallels with SARS-CoV-2. Almost 100% of dogs sero-convert within 21 days of exposure in affected kennels. Many dogs are asymptomatic, some develop 'kennel cough' and a small number are euthanased with severe bronchopneumonia. CRCoV represents a spontaneous beta-coronavirus model which shares many parallels with SARS-CoV-2 and can improve our understanding of genetic risk factors associated with mild and severe coronavirus infections. FELINE INFECTIOUS PERITONITIS (FIP) is a fatal multi-systemic inflammatory disease, occurring months to years after coronavirus infection. FIP shares features with COVID-19 associated Kawasaki-like syndrome in children. FIP is caused by a rare, in-host, mutation of a common feline enteric alpha-coronavirus, changing its tropism from epithelial cells to macrophages. Notably, the SARS-CoV-1 S gene is a mosaic containing FIP-derived sequence. FIP offers an excellent model to examine serious long-term consequences of coronavirus infection RESEARCH PROPOSAL: Utilising unique veterinary tissue archives from dogs and cats with spontanous coronavirus infections, we will use Whole Genome Sequencing (WGS) and RNA-Sequencing (RNA-Seq) to identify host genetic factors and transcriptomic events associated with severe complications of veterinary coronaviruses in dogs and cats. TRANSLATIONAL POTENTIAL: This is a collaborative 'One Health' proposal at the interface of veterinary and human medicine, so we are ideally poised to translate findings promptly.",2020,2021,Royal Veterinary College,256975.74,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2020 +C04604,ES/V010964/1,Impacts on social connections and wellbeing of COVID-19 policies in the Older Population: CFAS cohort Over 75s (OPPO),"The recent introduction of social distancing measures due to the COVID-19 coronavirus outbreak will have had a profound impact on older people's physical and mental health. At the same time there has been a fundamental shift in the use of online communication, both for informal contact with family members and online health consultations as well as for the functions of everyday life. The Cognitive Function and Ageing Study II (CFAS II) is a population representative longitudinal study examining the health, wellbeing, cognition, social networks and health and social care usage of older people in three diverse geographies of England including rural areas and those with high social deprivation. CFAS II began in 2009 but has recently completed (2018-2019) a 10-year follow-up interview with a sample of participants. During this follow up interview, measures of interest to this project, such as wellbeing, social networks, online communication and access to services were gathered. The research team are currently undertaking a new wave of interviews that will enable direct assessment of the mental health impact that social distancing measures have had on this vulnerable group along with any changes to communications and social networks that have occurred. The aim of this project is to analyse these effects, and to undertake a further follow-up interview to investigate the longer term impacts of the COVID-19 pandemic on this group of people; utilising extensive data collected from previous waves of the study. Aims: 1) To estimate the immediate and persistent impacts on mental health, wellbeing, general health of the COVID-19 pandemic; 2) To estimate social care usage and support received from others (family/neighbours etc.) and how this has changed over the course of the pandemic. 3) To examine changes in mobile, smartphone and social network usage by comparing data from previous waves, exploring to what extent there has been new usage as a result of the crisis and if this has persisted.",2020,2021,University of Cambridge,268833.42,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C04605,EP/V026488/1,VIPIRS - Virus Identification via Portable InfraRed Spectroscopy,"Spectroscopic techniques such as infra-red, Raman, and mass spectrometry have long been used to identify chemical compounds and biological species, including bacteria and viruses, usually in specialised lab conditions with high performance instrumentation. Virus identification in realistic clinical/field environments, using low cost instrumentation, is appealing, as it can be widely deployed and so is very suitable for diagnosis, prevention and management in pandemics such as COVID-19. However, low cost instrumentation produces poorly-resolved spectra with added noise. Our recent work has investigated machine learning algorithms applied to spectra from low cost near infra-red (NIR) spectrometers to extract identifiable patterns from targets with complex backgrounds and limited experimental control/processing. Our latest study shows that it is possible to use the technique to accurately differentiate respiratory syncytial virus and Sendai virus in different media, and quantify their viral loads. We aim to develop a spectrometer-fronted, cloud-based system for in-situ SARS-CoV-2 detection with three deliveries. The system will record spectra from patient nasal samples in the field and return a positive/negative diagnosis within ~ 1 minute, based on model-driven analytics running on a cloud-based service. The detection model will be developed, trained and validated using spectra from the SARS-CoV-2 virus in (a) lysis buffer and (b) nasal aspirate simulant; the model will then be used to determine whether the virus is present in the sample using a 'subsumption' operation in the learning algorithm. The system will be validated in real environments in collaboration with our partners in Northern Ireland Regional Virology Lab (RVL).",2020,2022,University of Ulster,529841.7,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04606,ES/V011286/1,Supporting the Business Response to COVID-19: Survey on Technology Adoption,"This research project builds the evidence base on technology adoption, and examines how government can best support businesses, in particular small and medium sized enterprises (SMEs), in the UK at a time of crisis. Working in collaboration with the Confederation of British Industry (CBI), this project will design and undertake a new survey of businesses across the UK to shed light on the extent to which, in response to the COVID-19 crisis, businesses have introduced new technologies or organisational practices that are considered ""productivity enhancing"" in normal times. It will seek to understand the drivers and impacts of such innovation, business perceptions on these, and the relative effectiveness of different business support policies from the perspectives of businesses themselves. Via a follow-up survey one year on (and linking to secondary data sources), we will examine whether such innovation persists into the longer run, its impact on firm survival, performance, employment and worker productivity; and how government policy might promote the persistence of productivity enhancing changes into the recovery phase. The first deliverable will be a report summarising the data, including analysis of heterogeneity by sector, region and firm type. The second deliverable will be a report summarising the findings of the combined initial and follow on surveys. Collaborating with the CBI in these bespoke business surveys will help to create relevant and informative questions on product and process innovation, enablers and barriers to innovation, and business views on potential policy levers for the recovery. The project will seek to inform business support policies to enable firms to survive, adapt and grow out of the current crisis.",2020,2022,London School of Economics and Political Science,147782.4,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C04607,MC_PC_20013,"Developing and Delivering targeted SARS-CoV-2(COVID-19) health interventions to Black, Asian and Minority Ethnic (BAME) communities living in the UK","COVID-19 pandemic appears to cruelly discriminate, inflicting a disproportionate burden of illness and death across Black and South Asian communities. There are concerns that unless targeted interventions are delivered the current pandemic will only serve to magnify existing social inequalities experienced by UK BAME communities. The research team has extensive experience in co-producing digital interventions to assist BAMEcommunities to navigate barriers and gain equal access to care. The current project aims to (a) design culturally specific health messages for Black and South Asian groups and (b)deliver these messages through specific trusted communication channels, in order to have the needed impact on behaviour change and reduce COVID-19 risk, targeting thefollowing: risk and susceptibility, proximity and social distancing and infection control, highlighted by our public and patient involvement. With the support of the local and regional BAME community groups, knowledgechampions (community and faith leaders) and knowledge advocates (from public health and allied health professionals), we will co-produce key written/visual documents, shortfilms up to 2 minutes (mainly for smart phone viewing) and mobile apps. The specific content of the messages will be a combination of public health advice and targeted, salient and culturally appropriate messages. We will evaluate the efficacy of our interventions. We will disseminate, share information and experience gained in a rapid and timely manner to support the behavioural change to mitigate the risk of infection by engaging with stakeholders, community leaders, policy makers, including NHS England and PHE.",2020,2021,Royal Surrey County Hospital NHS Foundation Trust,329152.53,Human Populations,Asian | Black | Other,Adults (18 and older) | Unspecified,Unspecified,Minority communities unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +C04608,EP/V026178/1,Tracking COVID cybercrime and abuse,"Around half of all acquisitive crime was already online before the start of the pandemic; it is now surging as many human activities move online chaotically, and cybercriminals adapt to the opportunities. This project will collect data at scale about online criminality, quickly enough to fetch malicious material before it is removed. We will not work alone but will promptly provide datasets to other researchers, and collaborate to create better analysis tools, analyse offender behaviour, and monitor the effectiveness of police and industry response. Our Cambridge Cybercrime Centre already collects data from underground forums, spam feeds, and industry partners, but we will ensure that pandemic related cybercrime Is prioritised and new datasets collected about online abuse and extremist views, such as anti-vaxxers. To scale up our work, we need to maintain and expand our network of honeypots and other sensors; extend our server cluster; scrape dozens more underground forums; and extend our collection of chat channels and illicit marketplaces - which are often found on Tor hidden services. We have an established ethical framework for data collection and a straightforward legal framework for data sharing, but a current bottleneck is that non-technical users can be swamped by what we provide, so we need to develop NLP tools to enable easier analysis of the data by researchers from other disciplines. We will also do our own analysis, for research to identify opportunities for law enforcement action, and to measure the effectiveness of responses by law enforcement and industry.",2020,2021,University of Cambridge,984270,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C04609,MR/V028480/1,COVID-19: Assessing the vulnerability of the fetus to SARS-CoV2 infection across development,"Numerous studies have shown, that pandemic coronavirus strains such as SARS enter the patient body through ACE2, a specific protein expressed in the airways. ACE2 is important for controlling blood pressure and it is increased in patients with hypertension and kidney conditions. Both of these groups are known to be more susceptible to severe SARS-CoV-2 infection. During the current COVID-19 pandemic, it has been observed that infants and children are less susceptible to severe infection, with extremely low numbers reported across the world requiring intensive care. Strikingly, newborns seems to be unaffected by this condition, even when the mother tested positive for COVID-19. While the data available are still limited, this has led the UK Governement to define pregnant women as a 'high-risk' group. Therefore, it is important to understand the mechanisms behind the low incidence of complications in fetuses and newborns. Our hypothesis is that the fetus is not susceptible to SARS-CoV-2 infection because it lacks the ACE2, in tissues that may be exposed to the virus during development and early postnatal care. Our study will provide the health service and advisory boards with new data, that will help inform updated guidance to pregnant mothers during the current pandemic.",2020,2021,University College London,17335.02,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C04610,MR/V027808/1,What TRIage model is safest and most effective for the Management of 999 callers with suspected COVID-19? A linked outcome study (TRIM),"NHS services are experiencing highly volatile demands for care as a result of the COVID19 pandemic, with initial contact often being a 999 call to the emergency ambulance service reporting coronavirus symptoms. Triage, determining each callers' treatment, is key to appropriate care provision and resource allocation. Undertriage of 999 calls may result in avoidable serious or critical illness or death; overtriage adds unnecessary increased pressure on secondary care services, diverts resources away from the most seriously ill and may expose patients to unnecessary risk of further infection at the hospital. Little is known about what model of triage works most safely and effectively in the context of a pandemic. We will survey all ambulance services In England, Wales and Scotland to categorise triage models used in call centres and on scene during the 2020 pandemic. We will work with selected ambulance services from each triage model type and retrieve anonymised linked outcomes for callers logged by services with COVID-19 symptoms; outcomes include death, hospital and ITU admissions, Emergency Department attendances, COVID19 diagnosis. We will also track 'backwards' to examine ambulance service records of patients admitted to hospital with a diagnosis of COVID-19 in order to identify any missed or undertriaged cases. We will also undertake semi-structured interviews with stakeholders in sampled services, to gain an understanding of experiences and concerns related to implementation, effectiveness and safety. We will deliver staged outputs throughout this study in order to inform policy and practice during later stages of the current crisis and any future pandemics.",2020,2022,Swansea University,233104.29,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C04611,MR/V021060/1,Development and Evaluation of a Training Package to support the Remote Assessment and Management of People with Movement Impairment and Disability,"The problem: Physical disabilities are common throughout life. Usually, hands-on detailed movement assessment results in a targeted rehabilitation plan, with ongoing evaluation required as needs change. During Covid-19, many people, of all ages, have received no rehabilitation, & rehabilitation need is escalating with recovering Covid-19 patients; creating a ""tsunami of rehabilitation need"" (1). In response, clinicians are rapidly adapting & creating telerehabilitation solutions to manage caseloads & prioritise those at risk of deterioration, with little specific guidance, training or support. Professional bodies & clinical networks highlight the marked variations in approaches used, expressing concerns about potential inequity & inefficiency. Our rapid literature review underlines this problem, citing lack of specific guidance/training as barriers to effective telerehabilitation implementation. This has immediate & long-term relevance given the ""new-norm"". Research aim: Develop a Toolkit & Training package for the current/future workforce, wherein telerehabilitation will be integral to assessment & management. Study Design: Knowledge to Action Framework, methodology commonly used in implementation science. Key steps include: (i) literature review to inform guidance/provide examples of best practice; (ii) national online survey to identify clinicians' needs, (iii) production & evaluation of the Toolkit through iterative cycles of data collection, evaluation & refinement (initially in the SouthWest); (iv) national roll-out/evaluation, (v) Production of final training package for use within clinical/educational arenas. Study outputs: Practical guidance, process pathways & training to optimise the confidence & competence of clinicians to effectively implement telerehabilitation in people with physical disability from across the lifespan.",2020,2022,University of Plymouth,143622.15,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Research on Capacity Strengthening,Cross-cutting,2020 +C04612,ES/V011057/1,Tracking Public Attitudes and Preferences for Post-COVID-19 Labour Migration Policies,"How are public attitudes towards foreign-born labour changing, and how can they inform policymaking which supports national recovery efforts across employment sectors and geographic regions? Public opinion research, which shows how major events sometimes contribute to shifts in attitudes, is key for understanding changes in the social and economic fabric of a country. Tracking attitudes' composition across groups and places, as well as dynamics over time, can contribute to more effective migration and labour market policies that reflect public understandings and preferences. This is especially true in the current crisis: COVID-19 has already motivated changes in political and media discussions about migrant workers, especially towards those in key occupations that are now considered fundamental to the country's response to the pandemic. Migrant workers comprise sizable shares of these occupations, and, crucially, many have jobs deemed 'low-skilled' that would not have qualified for work visas under current labour migration policies. Shifts in media and political narratives could reflect-or indeed cause-deeper shifts in public opinion towards migrant labour at all skill levels. However, we still do not know the magnitude of this change, whether it is homogeneous across different regions and sectors of the population, and whether it is short lived or the beginning of a longer-lasting shift. Addressing these questions as post-pandemic events unfold-and as the government has re-introduced its proposed Immigration Bill with modifications-will be crucial for understanding the transformation of the UK's society and economy due to COVID-19.",2020,2021,University of Oxford,212146.95,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C04613,MR/V027913/1,Prognostic models for COVID-19 to support risk stratification in secondary care,"As of mid-July 2020, almost 600,000 people have died with COVID-19 (coronavirus) worldwide. Some patients who are admitted to hospital with COVID-19 experience a rapid worsening of their symptoms and go on to need intensive care treatment, ventilation (to help them breathe) or die. Because the virus is new and affects different people in different ways, doctors find that their clinical experience is not enough to help them to predict which patients are most likely to develop severe symptoms or die, and there is no tool which can help them to do this. Therefore, the aim of our study is to develop tools that will help healthcare professionals to identify patients at high risk of needing intensive care treatment or ventilation, or of dying, as well as patients at low risk who can be safely discharged from hospital. This may provide an early opportunity to treat patients at high risk, while also making best use of limited hospital resources. We will do this by using anonymised patient data from hospitals in the UK to: 1. Develop a model which uses patients' symptoms, test results, and other information to predict their risk of needing intensive care treatment/ventilation, or dying. 2. Find groups of patients with similar test results and explore how their condition progresses.",2020,2021,University of Birmingham,66631.08,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C04614,EP/V026399/1,SCADs: Social Connection Awareness Devices to Reduce Isolation during Social Distancing,"This project's impact will be to benefit wellbeing and advice adherence during social distancing by supporting remote social relationships with lightweight communications devices. Teleconferencing systems such as Zoom or Teams relieve social isolation, but demand focused attention and largely fail to recreate the peripheral awareness supporting ongoing social connection in co-present situations. In this R&D project we will develop a series of dedicated Social Connection Awareness Devices (SCADs) that complement teleconferencing by offering undemanding, non-verbal communication to increase awareness of and feelings of social and emotional connection with remote friends and family. To allow immediate and widespread impact, SCADs will be circulated as self-build ICT products: electronic devices that people make at home using off-the-shelf electronic components, software downloaded from our website, and housings made from everyday materials. Highly accessible, illustrated instructions pitched to a similar skill level as online food recipes will guide their construction, and an online forum will support a community to grow around them. This strategy has already supported 1000s of people to build our designs in recent projects. We will release a series of monthly designs starting soon after the project starts; rapid development will be facilitated by developing shared hard- and software infrastructures. Each new design will be improved based on the large-n qualitative research made possible by previous ones into how different features of lightweight communication devices support social and emotional connections. SCADs will thus enhance the knowledge base in HCI and make timely impact with this relatively underdeveloped form of telecommunications.",2020,2021,Goldsmiths University of London,240385.05,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2020 +C04615,ES/V012657/1,The fiscal response to Covid-19: 'Thinking big' on tax policy after the crisis,"Around the world, the unprecedented public spending required to tackle COVID-19 will inevitably be followed by a debate about how to rebuild public finances. At the same time, politicians in many countries are already facing far-reaching questions from their electorates about the widening cracks in the social fabric that this pandemic has exposed, as prior inequalities become amplified and public services are stretched to their limits. These simultaneous shocks to national politics inevitably encourage people to 'think big' on tax policy. Even before the current crisis there were widespread calls for reforms to the taxation of wealth in the UK. These proposals have so far focused on reforming existing taxes. However, other countries have begun to raise the idea of introducing a 'wealth tax'-a new tax on ownership of wealth (net of debt). COVID-19 has rapidly pushed this idea higher up political agendas around the world, but existing studies fall a long way short of providing policymakers with a comprehensive blueprint for whether and how to introduce a wealth tax. Critics point to a number of legitimate issues that would need to be addressed. Would it be fair, and would the public support it? Is this type of tax justified from an economic perspective? How would you stop the wealthiest from hiding their assets? Will they all simply leave? How can you value some assets? What happens to people who own lots of wealth, but have little income with which to pay a wealth tax? And if wealth taxes are such a good idea, why have many countries abandoned them? These are important questions, without straightforward answers. The UK government last considered a wealth tax in the mid-1970s. This was also the last time that academics and policymakers in the UK thought seriously about how such a tax could be implemented. Over the past half century, much has changed in the mobility of people, the structure of our tax system, the availability of data, and the scope for digital solutions and coordination between tax authorities. Old plans therefore cannot be pulled 'off the shelf'. This project will evaluate whether a wealth tax for the UK would be desirable and deliverable. We will address the following three main research questions: (1) Is a wealth tax justified in principle, on economic or other grounds? (2) How should a wealth tax be designed, including definition of the tax base and solutions to administrative challenges such as valuation and liquidity? (3) What would be the revenue and distributional effects of a wealth tax in the UK, for a variety of design options and at specified rates/thresholds? To answer these questions, we will draw on a network of world-leading exports on tax policy from across academia, policy spheres, and legal practice. We will examine international experience, synthesising a large body of existing research originating in countries that already have (or have had) a wealth tax. We will add to these resources through novel research that draws on adjacent fields and disciplines to craft new solutions to the practical problems faced in delivering a wealth tax. We will also review common objections to a wealth tax. These new insights will be published in a series of 'evidence papers' made available directly to the public and policymakers. We will also publish a final report that states key recommendations for government and (if appropriate) delivers a 'ready to legislate' design for a wealth tax. We will not recommend specific rates or thresholds for the tax. Instead, we will create an online 'tax simulator' so that policymakers and members of the public can model the revenue and distributional effects of different options. We will also work with international partners to inform debates about wealth taxes in other countries.",2020,2021,London School of Economics and Political Science,136768.38,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C04616,MR/V036963/1,Development of a natural transmission model of COVID-19,"For the assessment of interventions against COVID-19, there are currently no alternatives to the use of animal systems that fully recapitulate a whole functioning body system. The initial focus on in vivo models for COVID-19, based on experiences of establishing animal models for the pathogenic coronaviruses which cause SARS and MERS, were with ferret and non-human primate models. However, recent results from international laboratories working on SARS-CoV-2 have highlighted that hamsters show a more distinctive COVID19 disease with clinical signs associated with respiratory infection (rapid breathing, weight loss, ruffled fur). In addition to the clinical signs, hamsters have also been shown to shed SARS-CoV-2 and infect their naïve cage mates. Developing the means of establishing and investigating this natural challenge model will provide important and beneficial testing protocols that can be used evaluate prophylactic therapies and vaccines via a natural infection route under experimental conditions, within a carefully controlled containment level 3 (CL3) envelope. This capability will also enable investigations on transmissibility between animals and studies on different strains, including those SARS-CoV-2 viruses that may be engineered by molecular virology techniques to address questions on virus host interactions. Hamsters appear to offer a valuable disease model for COVID-19. Importantly, establishing the hamster model and associated techniques to evaluate interventions in the UK at the unique CL3 facilities of PHE-Porton, will also support a rapid intervention screening and in vivo research hub for the country on COVID-19. This will support UK industry and academia's research need's and evidence base to progress into clinical trials",2020,2021,Department of Health and Social Care,260069.16,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C04617,MR/V028367/1,Controlling COVID19 through enhanced population surveillance and intervention (Con- COV): a platform approach,"Background: COVID19 is a rapidly evolving complex issue that requires near real time data, analyses and multidisciplinary team science to devise, implement and evaluate a wide variety of inter- and cross-sectoral interventions in order to minimise population harm. Aims: to integrate multiple sources of data to produce timely and responsive analyses to: 1) provide detailed insight into the evolving pandemic in the general population, vulnerable groups and diverse settings (health care workers, social care workers, care homes and schools); 2) support and undertake evaluations of the effectiveness of adopted counter measures as these evolve; 3) rapidly inform policy and practice decision makers; and 4) communicate effectively with the general public. Methods: We will build on the existing total population 3.2 million Wales Multimorbidity Cohort funded by HDRUK/MRC to create the greatest in-depth COVID19 population study with data enhancements on vulnerable groups and settings, serology and viral genomics, scale the breadth and depth of disciplines involved and support embedded evaluations of countermeasures. Our multi-agency team includes individuals from Welsh Government, Public Health Wales, academics from multiple disciplines and members of the public. Deliverables: Reports on exposure risks, incidence and outcomes to Welsh Government COVID19 Technical Advisory Group (TAG) and onwards to SAGE; share models with multiple UK groups including SPI-M, triallists, and the Royal Society DELVE initiative; and provide evaluations of natural experiments in policy and practice. Timeline: We will report weekly to TAG and monthly to funders, recognising the time- sensitive requirements needed to inform evidence-based control and exit strategies.",2020,2022,Swansea University,537314.67,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Social Workers | Health Personnel | Hospital personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Approaches to public health interventions",2020 +C04618,EP/V02874X/1,"Rapid, portable, and scalable Covid-19 antibody testing","Determining antibody levels in humans is crucial for monitoring immunity against Covid-19 and tackling the national crisis. Antibody levels report about a previous infection and help decide whether people can return to work or live with others without spreading the disease. To be effective for national screening, antibody testing should deliver accurate results to individuals ideally within minutes, and be portable as well as high-throughput. Existing techniques based on immunosorbent assays do not deliver these benefits due to the need for multiple liquid handling steps, signal amplification, insufficient accuracy, or read-out with bulky optical equipment. This project will deliver fast, portable, high-throughput and accurate antibody sensing by pioneering step-changing sensor nanopores from the lead PI at University College London Chemistry (UCLC), and by integrating them into memory-stick-sized on-the-market kits from industrial partner and biotech unicorn Oxford Nanopore Technologies (ONT). These MinION analysis kits have ushered in a revolution in portable DNA sequencing and are currently used for unravelling the Covid-19 sequence. The PI has a strong working relationship with the company and has licensed sequencing pore technology which has been one key component to make the MinION a success. In this project, the technology will be adapted with wider nanopores tailored for Covid- 19 antibodies. The new sensor pores can be plugged into the existing MinION kits without the need for redesigning the device, thereby ensuring production to scale. The devices will be clinically tested and benchmarked by Co-PI and intensive care and monitoring specialist Prof. Mervyn Singer at UCL Medicine (UCLM). All project partners have previously successfully worked together in joint grants, for publications, or via technology licensing contracts.",2020,2022,University College London,562949.55,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04619,AH/V00882X/1,Modelling and Supporting Recovery of the UK's Experience Economy: Enhancing Audience Resilience and Engagement via Digital Methods,"This proposal seeks to reconceptualise consumer value and business resilience in the UK's creative and visitor sectors and their value chain (from VFX companies, theatres and museums to festivals, catering and accommodation providers), collectively referred to as the experience economy. With a value of over £300bn, the health of the experience economy maintains the UK's status as the world's seventh most visited country and producer of quality creative experiences. Prior to the COVID-19 pandemic, many experience economy operators in the creative sector had begun experimenting with online content. Over the course of the pandemic, the range of these offers has expanded, opening up new audiences and sustaining existing ones. For many businesses, the digital or online 'experience' comprises mainly recorded and distributed content, usually provided free. Experiences are heavily dependent on evoking a sense of place. Therefore, at a time when access to physical places is restricted, there is a risk that online material fails to provide an effective proxy for the experience itself. While proving popular during the pandemic (see bibliography), existing products arguably offer limited additional experiential or business benefits. Convening expertise in experience design, post-production technology, games, visitor economy and place-making, this project will: - support experience providers in developing online and digital products which enhance their physical counterparts. - investigate modes of delivery and monetisation, as well as the policy instruments required to maintain adjacent place-based reputations and offers. - produce tools to support experience economy businesses' immediate post-COVID-19 regeneration, including scenario modelling, enabling a robust economic recovery.",2020,2022,University of the Arts London,685726.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C04620,MC_PC_20018,Development and manufacture of an improved replication-deficient simian adenoviral vector to prevent COVID-19,"The University of Oxford and Vaccitech jointly developed and then exclusively out-licensed a serogroup E chimpanzee adenoviral vector vaccine encoding the SARS-CoV-2 spike glycoprotein to AstraZeneca. This vaccine, ChAdOx1 nCoV-19, given as a single dose, has moved into Phase 2/3 studies in the UK, and in August 2020 begins Phase 3 studies in the US and Brazil. There are concerns that anti-vector immunity to the ChAdOx1 backbone may limit early boosting responses, or even boosts given on a yearly basis. Vaccitech has developed an alternative serogroup C chimeric gorilla adenoviral vector vaccine (""GAdVac""), which has been shown in completed murine studies to elicit higher antibody and T cell immune responses than the ChAdOx1 candidates. Vaccitech is now developing the full-length spike glycoprotein encoding GAdVac candidate and will use this as both a stand-alone vaccine and evaluate the use of this candidate as a prime and a boost for the ChAdOx1 platform. Efficacy studies in ferrets will be pursued with Public Health England at Porton Down. The pre-master virus seed will be produced in the SOP- controlled Early Development Laboratories at Vaccitech in Oxford, and then transferred to Advent (Rome, Italy) for GMP manufacture. Advent has successfully made three GMP released lots of ChAdOx1 vectors for Vaccitech. Scientific advice will be sought from MHRA, and a formal GLP toxicology study will be performed due to the novelty of this vector. Within 12 months, the CTA to begin a Phase 1 immunogenicity study will be complete.",2020,2021,Vaccitech Ltd,100510.35,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C04621,ES/V012754/1,Quantifying and Simulating the Impact of Social Distancing Policies on Firm-Level Productivity,"This project analyzes the impact of social distancing policies in the workplace in the UK on firm- and organization level productivity. The economic cost are likely to be heterogeneous across firms and sectors as well as across regions as space use intensities vary systematically across the UK, giving rise to the possibility of COVID19 to significantly exacerbate regional economic inequalities raising the necessity to develop more cost-effective and targeted support measures to firms. To do so, the project will produce a novel data product jointly with the ONS to be subsequently hosted and analyzed on the ONS Secure Research Service. This data product will bring together detailed information on the physical make up of the population of the UK's premises in which economic activity takes place along with detailed information on employment, turnover and producivity at the premise level by combining the ONS's Inter-Departmental Business Register (IDBR) with the Valuation Office Agency business rates valuation lists of physical premises. The data product is then subsequently studied through the lense of an economic model that will incorporate ""physical space"" as a factor of production in the estimation of production functions and empirically calibrate an already developed theoretical model. The empirically disciplined model will both help quantify the economic impact of the existing social distancing policies as well as allow the simulation of the economic cost of counterfactual social distancing policies across firms, sectors and regions of the UK helping identify policies that may be effective in reducing both the economic impact while mtaintaining disease containmentment objectives.",2020,2021,University of Warwick,138159,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Economic impacts,2020 +C04622,BB/V011456/1,Molecular mapping of SARS-CoV2 and the host response with multiomics mass spectrometry to stratify disease outcomes,"This project forms part of an international level effort to understand the mechanisms of COVID-19 disease in the global population. Despite the considerable insight gained into the virus,SARS-CoV-2, at the genetic level, the key facets of the virus structure and its pathogenic effects remain to be determined. Equally molecular descriptors that contribute to disease progression are poorly defined, and have not yet been considered in testing strategies. Mass spectrometry (MS) can provide rapid, precise and reproducible diagnostic information at the molecular level (multiomics) that complements genomic information. In this project we will use MS to profile patient response to COVID-19 (with samples from NHS partners). This research will be exploited by our industrial project partners for diagnostic/prognostic testing protocols and for the development of vaccines and therapeutics. Research will constitute the UK effort in an international coalition initiated by the PI, COVID-19 MS, (currently over 600 members in 28 countries) who have agreed to share experience, protocols, materials and data. This next generation measurement approach is both transferable and accessible and through replication studies involving multiple partner labs we will overcome the accuracy, sensitivity issues of current lab- based approaches while also providing population data about individual risk to COVID-19. Our multiomics approach allows detailed structural information of the virus and its effect on the host using an intrinsic physical property - mass - unlike the indirect lab approaches currently employed. Outputs are multifold: we will refine testing approaches, stratify treatment options, determine isolation requirements and bring much needed speed into measurement aspects of novel therapeutic development programmes - for COVID-19 and future threats. Through our expertise in biomarker discovery and validation to profile disease mechanisms we possess the processing pipelines to extract maximum understanding from the data. As world leaders in protein structure analysis, we will structurally characterise virus:cell interactions, informing vaccine design and therapeutic intervention. Knowledge gained will be translatable to hospital testing laboratories for targeted assays, to biopharmaceutical companies for vaccine and therapeutics development, and for the development and quality control of reagents for biomarker or serological tests. Working with LGC Ltd. diagnostics and measurement companies (Waters, Thermo, Sciex, Bruker) and through CAMS the Community for Analytical and Measurement Science major Pharmaceutical companies (Pfizer, AstraZeneca , GSK, and Allergan) we will be able to scale up our methods and translate the outcomes to provide targeted assays to the NHS for biomarkers, to validate serological tests and for vaccine and therapeutic development embedding future resilience. The international effort is purposefully geographically spread allowing regional NHS lab access to enable rapid implementation. Finally, we established the COVID-19 MS Coalition to share sample processing protocols and to make all curated datasets open and accessible for global effort to combat this disease.",2020,2022,The University of Manchester,2364895.08,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C04623,BB/V011324/1,"Generation, characterisation and application of SARS-CoV-2 protein antigens for COVID-19 rapid diagnostic purposes in the hospital and community","We aim to generate a range of stably transfected cell lines to help meet the demand for quality-verified recombinant SARS-CoV-2 structural proteins, which are desperately needed, and which we will use, to help in the development of diagnostics and vaccines. In so-doing our project will complement and expand the repertoire of proteins available on the COVID-19 Protein Portal. The platforms we establish will also be perfectly positioned for the rapid generation of other targets in the future. We will produce these in two different mammalian expression systems, CHO and HEK293 cells, characterise these by mass spectrometry and undertake glycosylation analysis of the Spike glycoprotein. In producing non-glycosylated forms of the protein for comparison, we will define the importance of this post-translational modification for folding, assembly of the trimer form and the ability of the protein to detect anti-spike antibodies from recovered COVID-19 patients. The recombinant authentic and characterised forms of the SARS-CoV-2 proteins will be assessed in diagnostic assays in development with our industrial partner Mologic, and in ELISA assays in the East Kent Hospital Trust at Ashford to profile antibody responses across recovered COVID-19 patients. The proposed research will address the WHO 'coordinated global research roadmap 2019 Novel Coronavirus Global Research and Innovation forum' that stipulates the need for reagents that support the development of 'reliable serological testing as well as assays that monitor response and midterm support development of diagnostic products to improve clinical processes to contribute to control/point of care' and for development of vaccines.",2020,2021,University of Kent,534053.55,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C04624,MR/V028529/1,Optimising Wellbeing during Self-isolation (OWLS),People with severe mental health problems are at increased risk of being affected by COVID-19 and the pandemic restrictions. This is because they are more likely to live in impoverished circumstances and are less likely to be able to access the internet. Many people with mental health problems have physical health problems also which may mean they are in a group that needs to isolate for long periods of time. In this project we want to look at how people with mental health problems are affected by the current pandemic. We want to know whether people are able to access health services when they need to. Whether they are able to use the internet to access services and contact friends and if they are feeling lonely. Finally have they made any changes to reduce the risk of COVID-19 such as stopping smoking. The project involves completing questionnaires and taking part in interviews. We will invite people who took part in the Health and Wellbeing Survey and said they were interested in taking part in future research. The results of the study will be used to make recommendations about how best to support people with severe mental illness during a pandemic.,2020,2021,University of York,127323,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04625,MR/V028502/1,"IMPACT OF COVID-19 PANDEMIC ON CARE HOME PATHWAYS, OUTCOMES AND SAFETY OF CARE","The COVID-19 pandemic seriously affected care home residents leading to a doubling in the number of deaths with the North East being particularly badly affected. This research will seek to understand how residents who fell ill (with COVID-19 or non-COVID-19 conditions) during the pandemic were managed and whether this was different from 'normal' circumstances. Were more residents cared for within homes and not taken to Emergency Departments? Were residents transferred back from hospital with COVID-19 symptoms? Did COVID-19 change how decisions were made by care home staff? First we will gather data for individuals in the North East which includes data collected while in care homes, Emergency Department visits and other hospital admission data. This unique dataset will allow us to examine changes and outcomes of care for residents from before, during and after the easing of lockdown. Subsequently we will interview care home staff and community clinical staff to understand how their decision making changed during the pandemic and how this affected care home residents. We will collate the findings to develop recommendations for future guidance and policy on how care homes react in pandemic outbreaks and on broader strategies for health provision for the care home population.",2020,2021,Lancaster University,162171.06,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C04626,MR/V028421/1,Efficient geostatistical sampling to estimate the fraction of the population recovered from Covid-19,"The Covid-19 pandemic has a long course to run. Its successful management by governments and other international agencies will require statistical tools for real-time monitoring of the evolution of the pandemic over space and time. How covid-19 spreads across an urban area over time, for example whether there are small or large numbers of clusters, how large they are spatially, and how rapidly they grow, is poorly understood. Understanding local phenomena can also support other research programmes and provide evidence to support future lockdown policies, for example how localised lockdowns need to be (city-wide versus neighbourhoods) and for how long. Local authorities may also use this evidence in support of highly targeted partial lockdown policies (such as differential application of the national Covid alert scale for different areas). Data sources that identify the location of cases can be used to generate predictions of the spread of Covid-19 cases over time and space, which will facilitate the implementation of localised policies to contain the spread of the virus. The aim of this project is to adapt statistical methods for this purpose and develop software for their implementation. This project will develop software for the real-time surveillance of Covid-19 that can be used with any georeferenced and time stamped data. We will use data on hospital attendances and admissions for Covid-19 to develop, calibrate, and test our software and models. We will build on state-of-the-art geostatistical software developed by the co-applicants to produce estimates and predictions of incidence or the ""R number"" across an area of interest based on available data sources. These outputs can also support the design of scheme to sample the population for testing when such programmes are rolled out, for which we will also include functionality.",2020,2020,University of Birmingham,22356.99,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C04627,ES/V012789/1,"Understanding the economic, social and health impacts of COVID-19 using lifetime data: evidence from 5 nationally representative UK cohorts","There is an urgent need to understand the economic, social and health impacts of the COVID-19 crisis, the extent to which it is widening or narrowing inequalities, and the lifelong factors which shape vulnerability and resilience to its effects. We propose survey data collection and novel linkages in the UK's unique series of five national longitudinal cohort studies which have captured detailed social, economic, developmental, behavioural, attitudinal, and physical and mental health data on large representative samples since birth. The cohorts cover key life stages from late adolescence (19/20), early adulthood (30/31), mid-life (50) and older age (62, and 74). A rapid first COVID web-survey was successfully issued in-house in all five cohorts in May 2020 (n=18,148). We propose two further web surveys in August and November 2020, to capture the evolving circumstances of study participants across multiple life domains, including in health, work, and social life. This will be combined with the rich social and biomedical life course data already collected within these cohorts, to identify inequalities in the short, medium and long-term effects of the crisis, and to understand how different lifetime trajectories either mitigate or exacerbate its effects. Novel data from a COVID symptoms tracking app, and a range of geo-environmental indicators including green space and air pollution will also be linked. The latter are hypothesised to modify the mental and physical health effects of the crisis. The data collected will be made rapidly available to researchers via UK Data Service, and a series of policy briefings, and academic papers will be produced.",2020,2022,University College London,1436320.83,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C04628,ES/V012851/1,Optimising General Public Uptake of a Covid-19 Vaccine: A Mixed Methods Study (OPTIMUM),"The Covid-19 pandemic of 2020 has disrupted people's daily lives in many parts of the world, including in the UK, and it has caused many people to become ill and even die. Scientists, policy makers and the general public hope that a Covid-19 vaccine will developed soon, to help to prevent the spread of Covid-19 in future. As with any vaccination, it is very important that the public are confident in the vaccine so that most people will want to choose to have the vaccine. A high uptake of the vaccine is needed to protect as many individuals from becoming ill as possible, and to stop the spread of the virus. Recent studies suggest most people want a vaccine, but a minority of people are uncertain about whether they would want to be vaccinated against Covid-19. This seems to be because some people are worried about the safety of a new vaccine or do not have trust in the benefits of vaccination more generally. We want to understand more about what people see as the upsides and downsides of a new Covid-19 vaccine. This information will help to design a vaccination campaign that is trusted by people because it tells them what they want to - or need to - know before making a decision about having the vaccination. A good vaccination campaign would help to increase vaccine uptake, and help people separate facts about the vaccine from misinformed stories. To understand what hopes and worries people have about a Covid-19 vaccine, we plan to do a study on people's attitudes towards a new Covid-19 vaccine. The study will have four parts. In the first part, we will interview 12-15 key people involved in vaccine policy and in providing vaccines in different parts of the UK. The interviews will ask about: plans for vaccine roll-out; expected barriers and facilitators to vaccine uptake; communication challenges; key messages, channels and target groups, including professional and public; and any helfpul learning from other countries and other campaigns. In the second part, we will ask a sample of around 2,250 adults in the general population across Great Britain to take part in a survey about Covid-19 and a vaccine to prevent it. The people we ask will be a random sample of people who have taken part in the British Social Attitudes Survey in the past. The survey will include questions in five key ares: (1) typical behaviour in the past for other vaccines (e.g. annual flu vaccination, childhood vaccination); (2) general attitudes to vaccination; (3) experience of Covid-19 infection and whether people feel they are likely to get Covid-19 in the future (e.g. tested positive, suspected infection, contact with people with Covid-19 through their work, being in some of the groups that were asked to 'shield'); (4) attitudes and beliefs towards a new Covid-19 vaccine (e.g. safety, effectiveness, accessibility, necessity, trust, sources of information about vaccination, responsibility to others); and (5) people's intentions (e.g. whether they think they would agree to be vaccinated). Participants will also be asked about views and use of the NHS Tracking App. In the third part, will will invite a smaller sample of about 30 people, including some people at higher risk of Covid-19, to take part in more in-depth interviews so that we can understand their hopes and concerns about the development and roll-out of a Covid-19 vaccine in much more detail. In the last part of the study, we will go back to key people involved in vaccine policy and in providing vaccines in different parts of the UK and invite them to workshops so that they can hear about the study findings and use these to shape their information and plans to support high uptake of the vaccine.",2020,2021,University of Stirling,345254.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy,2020 +C04629,MR/V028979/1,ISARIC Clinical Characterisation Protocol UK (CCP-UK) - a companion study for patients with Cancer and COVID-19 (CCP-CANCER-UK),"2019 a new virus called SARS-CoV-2 emerged, which causes a disease termed COVID-19. This is often mild but can also be severe, leading to viral pneumonia; about one in 100 infected people are expected to die of i t. However, cancer patients are likely to be at higher risk of infection and death as they have a weakened immune system as a result of either their treatment or their cancer. We will tackle many urgent questions that need answering in cancer patients to help ensure early diagnosis, that the correct shielding advice i s given, and to enable doctors and patients to make informed decisions regarding treatment during the pandemic. This will be achieved by collecting detailed data from the over 5,000 cancer patients recruited into the main UK study which has described COVID-19 (CCP-UK study). The cancer data when linked with the rich COVID-19 data will enable the following important questions to be answered: What proportion of cancer patients die from COVID-19? How does this vary based on cancer type and cancer treatment? What are the symptoms cancer patients develop with COVID-19? Does this vary based on type of cancer and treatment? What type of cancer treatments puts people at higher risk of severe illness and death? What kind of healthcare resources are needed (including intensive care) to treat COVID-19 in cancer patients? How do the outcome of patients with cancer compare with non-cancer patients taking into account age and other illnesses?",2020,2022,University of Liverpool,222479.85,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C04630,EP/V031589/1,"Rapid catalytic disinfection of surfaces, PPE and transportation","Cardiff University and Selden Research have a patented novel catalytic method of making long lived reactive oxygen species effective for pathogen kill and surface disinfection. https://patentimages.storage.googleapis.com/12/c4/b7/8f1ef5827dc436/GB2572364A.pdf The method involves passing an environmentally benign solution containing dilute hydrogen peroxide (H2O2) using a spray bottle through a catalyst (a copper salt on alumina matrix) incorporated in the nozzle. We have tested this with a range of microorganisms including Staphylococcus aureus and Candida albicans yeast and have achieved 99.999% reduction in minutes. To date we have not examined virucidal activity but given the effect of our method on other microorganisms we anticipate it will be effective against enveloped viruses. Our work until now focussed on developing the method for the food preparation and agricultural industries and the key point is that no toxic residues remain on the surfaces that are treated, while also offering exceptional kill efficacy and compatibility with the surfaces treated. The research programme will initially test the virucidal activity of our existing formulation on viruses including coronavirus standard test strain as a surrogate for SARS-CoV-2 (COVID-19). We will then aim to modify and simplify the formulation to determine if we can replace hydrogen peroxide by air whilst maintaining the virucidal activity. We will also develop the use of aerosols so that the new method can be used to treat large spaces which could be applied in the disinfection of PPE for reuse or the environmentally non-toxic disinfection of transportation such as the internal spaces of ambulances, buses, trains and planes.",2020,2021,Cardiff University,212682.3,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C04632,MR/V028499/1,Safety and lower airway immunogenicity of two candidate Coronavirus Disease (COVID-19) vaccines administered to the respiratory tract,"For a COVID-19 vaccine to have maximum impact, it should not only prevent severe infection but also limit the shedding of virus so that transmission is interrupted and pandemic spread is controlled. Experience with the influenza vaccine FluEnz (which is given as a nasal spray) has shown that intranasal vaccines can be effective for both outcomes. All COVID-19 vaccines currently being trialled are delivered by injection but it is known that directly stimulating immunity at the site of infection (i.e. the nose and lung) induces specialised protective responses that may more quickly and completely control infection. This study will test the two leading UK COVID-19 vaccines to show that they are safe, well-tolerated and capable of stimulating immune responses both in the blood and the lung when administered to the respiratory tract. Using standardised methods, we will directly compare immune responses in the blood, nose and lower airway between these two vaccines as well as with data from ongoing clinical trials of intramuscular vaccination. Thus, we will show the effect of different vaccine technologies as well as delivery method and provide the critical information required to begin further clinical trials to show the efficacy of this needle-free vaccination strategy.",2020,2022,Imperial College London,376989.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +C04633,EP/V038141/1,De-risking dentistry: Quantifying aerosols associated with routine dentistry to inform mitigation technology and operating practices,"This project brings together internationally leading expertise in multiphase flows with key stakeholders working to develop evidence to underpin new protocols for safe delivery of UK dental care in the light of covid-19. Aerosol Generating Procedures (AGPs) are ubiquitous in dentistry due to mixed streams of air and water used as coolants during instrumentation. This coupled with evidence that oral fluids contain high levels of viral particles rapidly led to dental AGPs being identified as a critical transmission risk during the current pandemic and all routine UK dental care stopped. In this project, we will first characterise aerosols formed during the most common dental AGPs, (high-speed and low speed cutting of tooth substrate and ultrasonic dental scalers used for dental cleaning). High speed photography combined with appropriate illumination will be used for aerosol characterisation. The illumination angle and strength and image recording speed will be optimised for quantification of aerosol concentration and aerosol dispersion speed and distance from the source where the aerosol cloud can disperse. Then, measurements will be conducted in clinically relevant environments using training mannequins with ambient air exchange, enclosure size and operatory furniture reflective of different care settings. Following establishment of base-line aerosol behaviour for current care practices, mitigation steps, including modifications in air/water supplies to instrumentation, reduction in cutting speeds, high volume aspiration parameters and ambient air flow, will be explored. The direct involvement of clinical experts, virologists, public health policy researchers and instrument manufacturers will ensure that findings are rapidly considered.",2020,2021,Imperial College London,85254.81,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Dentists and dental staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +C04634,MR/V028618/1,"An analytical framework for Test, Trace and Isolate in the UK: optimising and targeting deployment alongside other measures.","We will develop a robust analytical framework to guide decisions about the deployment of Test, Trace and Isolate (TTI) to control the SARS CoV2 epidemic over the next 12 months. As the UK eases lockdown and workplaces, leisure venues and schools re-open, refining and targeting TTI is necessary to prevent the return of rapid exponential epidemic growth. This will require quick feedback, assessment and integration with real-time epidemiological, behavioural and operational data. We will develop mathematical models of SARS CoV2 transmission and TTI processes, to assess how TTI could be most effectively refined and targeted in association with other control measures, and to develop metrics to assess TTI performance. We will consider how both the design of the TTI system and environmental factors affect people's behaviour. We will respond to emerging questions but currently prioritise: 1) optimal combinations of TTI, screening and physical distancing measures, both to reduce transmission and to protect vulnerable groups; 2) appraisal of the role of behavioural responses to take up and adhere to TTI policies, including trade-offs and the consequences for how policies are supported; 3) signals to initiate stepped up intervention intensity; 4) assessment of our understanding of transmission patterns.",2020,2021,London School of Hygiene & Tropical Medicine,268335.48,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C04635,EP/V033670/1,Visual Analytics for explaining and analysisng contact tracing networks,"Contact tracing networks carry invaluable information for researchers to understand the spread of the virus, for policy-makers to control the COVID-19 outbreak, and for the government and the media in informing the public in rich ways. However, current data science tools fall short for the exploratory and explanatory analysis of the temporal, spatial and social aspects of these networks, and little is known on how most effectively the results of such analyses can be communicated broadly. This lack of a toolbox leads to organisations wasting resources on developing partial solutions designed without broad stakeholder engagement. To this end, this project aims to follow a user-centred approach to develop visual analytics methods for the analysis of large collections of contact tracing networks along with techniques for the communication of analysis results in transparent, comprehensive, yet engaging ways. Contact networks come with noteworthy technical and ethical challenges: inherent uncertainties due to the variation in their generation mechanisms, e.g., apps, hospital records, by volunteers; and high volumes of complex and sensitive information represented as event-based interactions with spatio-temporal facets. This project responds to these challenges through two deliverables comprising visualisation methods working simultaneously at group and individual levels while communicating the general trends in the spread: - Visualisations aimed at experts for understanding collections of contact networks to inform public health policies and make in-depth investigations without compromising individuals' privacy. - Visualisations for communicating analysis results with the general public for information and evidencing policy recommendations with representations having a purely explanatory emphasis.",2020,2022,Swansea University,372886.11,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Communication,2020 +C04636,EP/V029762/1,SUrfaCe Characteristics Enabled StrategieS against virus transmission (SUCCESS),"We propose to mitigate the transmission of COVID-19 between humans by development of antiviral formulated products. It will be delivered via additives in domestic formulated products, e.g. spray or aerosol, or integrated with current manufacturing processes, forming an invisible and long-lasting film of sub-micron thickness. Unlike disinfectants, formulations will be designed to both capture the aerosol droplets and inactivate the virus. Our first priority is to establish a mechanistic understanding of the interactions between aerosol droplets (or pure virus particles) and surfaces, which will inform possible antiviral mechanisms while providing a set of fundamental and coherent design principles for antiviral surfaces. Two technology platforms will be pursued to leverage the expertise and capability of our industrial partners. Polymer additives with controlled chemistry and molecular architecture will be explored to generate molecular films that facilitate disruption of aerosolised droplets and which may rupture the viral envelope or interfere adversely with key viral proteins and or genetic material. Proposed nanocellulose additives will confer additional benefits in terms of providing a porous structure designed to wick and absorb any protective mucus present. In parallel, hybrid polymer technology will be developed, employing reactive oxygen-producing copper nanoparticles coupled with flavin dyes that produce singlet oxygen species known to deactivate viruses when irradiated with light of the appropriate wavelength. Upon satisfactory antiviral testing results, promising design/formulation will be recommended based on their processability, suitability for end-applications, and environmental impact. Industrial partners with substantial experience in formulation will carry out pilot-scale production and full- scale manufacturing subsequently.",2020,2022,University of Birmingham,828886.92,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C04637,EP/V036777/1,Risk EvaLuation fAst iNtelligent Tool (RELIANT),"This project brings together unique expertise in Computational and Experimental Fluid Dynamics, Model Reduction and Artificial Intelligence, to identify solutions for the management of people and spaces in the current pandemic and post lockdown. A new interactive tool is proposed that evaluates the risk of infection in the indoor environment from droplets and aerosols generated when breathing, talking, coughing and sneezing. This capability will become more critical as winter approaches and building ventilation will need to be limited for comfort considerations. The fluid dynamic behaviour of droplets and aerosols, the effect of using face masks as well as other parameters such as room volume, ventilation and number of occupants are considered. A datahub capable of storing, curating and managing heterogeneous data from sources internal and external to the project will be created. A synergetic experimental and numerical approach will be undertaken. These will complement the existing literature and data from other EPSRC-funded projects providing suitable datasets with adequate resolution in time and space for all the relevant features. To support experiments and numerical simulations, reduced order models capable of interpolating and extrapolating the scenarios collected in the database will be used. This will permit the estimation of droplet and aerosol concentrations and distributions in unknown scenarios at low-computational cost, in near realtime. A state-of-the-art AI-based framework, incorporating descriptive, predictive and prescriptive techniques will extract the knowledge from the data and drive the decision-making process and provide in near real-time the assessment of risk levels.",2020,2022,University of Glasgow,1731627.63,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing | Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2020 +C04638,AH/V00994X/1,COVID-19: Impacts on the cultural industries and implications for policy,"This project brings together the Centre for Cultural Value, the Creative Industries Policy and Evidence Centre and a national consortium of researchers and partners to analyse existing datasets and conduct targeted empirical research on the impacts of the COVID-19 crisis on cultural organisations, practitioners and audiences. It will provide a clear national picture and identify immediate and longer-term implications for policy and practice. We will map and track the sector longitudinally over 18 months using a mixed-methods design to assess the extent of organisational exit and sectoral adjustment, as well as evolving cultural engagement behaviours amongst the public. We will use a workstreams approach to provide a holistic and nuanced analysis of the impacts of COVID-19 on the cultural industries. Workstream 1 will produce a meta-analysis of cultural sector surveys relating to COVID-19, bringing together the fragmented datasets observed to date, and developing a range of illustrative, representative case studies from the core sub-sectors of the cultural industries. Workstream 2 will examine cultural supply and demand in the digital space, incorporating a longitudinal tracking survey, social media analysis and analysis of content uploaded to an online community-based storytelling platform. Workstream 3 will analyse the impacts of UK policy responses and compare international policy responses. It will include a case study of a regional cultural ecology; examine impacts of intervention packages made available by the UK governments and funders; and convene a reference group of c.20 cultural industry membership organisations, trade associations, advocacy bodies, funders and policymakers.",2020,2021,University of Leeds,997117.11,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C04639,EP/V032658/1,COVID-19: TRACK: Transport Risk Assessment for COVID Knowledge,"Public Transport (PT) patronage is currently well below the norm, but as restart progresses the number of people using transport systems will increase. This could increase COVID-19 infection due to increased proximity and interaction with infected persons and contaminated surfaces. TRACK will develop a novel risk model that can simulate infection risk through three transmission mechanisms (droplet, aerosol, surface contact) within different transport vehicles and operating scenarios. Our interdisciplinary team will collect new data concerning buses, metro and trains (Leeds, Newcastle, London). We will collect air and surface samples to measure SARS-Cov-2 prevalence together with other human biomarkers as a proxy measure for pathogens. We will characterise user and staff travel behaviour and demographics through surveys and passive data collection to relate PT use to geographic and population sub-group disease prevalence. Quantifying proximity of people and their surface contacts through analysis of transport operator CCTV data will enable simulation of micro-behaviour in the transport system. Physical and computational models will be used to evaluate dispersion of infectious droplets and aerosols with different environmental infection control strategies. Data sources will be combined to develop probability distributions for SARS-CoV-2 exposure and simulate transmission risk through a Quantitative Microbial Risk Assessment (QMRA) framework. Working closely with Department for Transport (DfT) and transport stakeholders, TRACK will provide microbial and user data, targeted guidance and risk planning tools that will directly enable better assessment of infection risks for passengers and staff using surface PT networks, and help policy teams design effective interventions to mitigate transmission",2020,2022,University of Leeds,1754527.71,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2020 +C04640,MR/V028596/1,The impact of the COVID-19 pandemic on people with learning disabilities and factors associated with better outcomes,"There are about 1.5 million people with learning disabilities across the UK. Even before the COVID-19 pandemic, people with learning disabilities were more likely to experience poorer health and wellbeing, restricted social lives and loneliness and poverty. The social retsrictions and changes in support during the COVID-19 pandemic may have made this worse. In this project we will ask 1,000 people with mild/moderate learning disabilities, and the carers of 500 people with severe/profound learning disabilities, about their wellbeing, health, living circumstances, the support they are getting, and the impact of COVID-19 on their lives. We will go back to people three times over the 12-month project so we can see if anything is changing over time and what is linked to better experiences for people. We will also ask extra questions about urgent issues that come up during the course of the project. These will be decided by working with collaborating organisations of people with learning disabilities and family carers, policy-makers and other organisations across the UK. We will analyse the information each time we run the survey so we, with collaborating organisations, can get information quickly to the wide range of people and organisations who can use it.",2020,2021,University of Warwick and Lancaster University,492412.35,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C04641,ES/V013017/1,"Assessing the impact of COVID-19 on young peoples' learning, motivation, wellbeing, and aspirations using a representative probability panel","The COVID-19 pandemic has led to an unprecedented challenge for pupils, parents, schools, and policy makers, with many children returning to school in September for the first time after six months at home. Our new project will collect and analyse high quality data on young people (ages 12-19) in England using an existing representative sample to assess the impact of the cancellation of exams, home learning experiences, and returning to school during the COVID-19 pandemic on pupils' learning, motivation, wellbeing, and aspirations. This will be a follow-up of an established stratified random sample, the Science Education Tracker (SET). Data collection will be delivered online by Kantar, who carried out the original fieldwork, with explicit permission from 5,991 respondents for re-contact. These data, which we will link to the National Pupil Database, will provide a unique opportunity to answer the following pressing research questions separately by SES, gender, and ethnic group: 1) Has the cancellation of examinations had differential impacts on wellbeing and motivations? 2) Has this changed pupils' aspirations for further study and future careers? 3) Has home-schooling affected pupils' transitions into further and higher education? 4) What role do young people's experiences of home learning under lockdown and returning to education play in this? Led by Professor Lindsey Macmillan, with Professor Patrick Sturgis, Dr Gill Wyness, and Dr Jake Anders, the team combines world-leading expertise in design and analysis of large-scale survey data with disciplinary expertise in educational inequalities. We will partner with the Department for Education and Wellcome to ensure the co-production of policy-relevant evidence. This will fill an important gap in our understanding of the experiences of young people and the impact on their motivations, wellbeing and aspirations during this unprecedented period.",2020,2021,University College London,267729.18,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C04642,BB/V011448/1,The Genetics of Symptom Severity in COVID-19 Infections,"Copy number variation (CNV) is an important class of genetic variation that can have large impacts on human health. There is a significant amount of knowledge on genomic disorders caused by rare CNVs at specific locations in the genome and a good amount of evidence into the role of common CNVs across a variety of human traits. To date progress on large scale CNV association studies from Exome or Genome sequence data has been limited by methodological constraints and/or technological limitations. The majority of CNV associations studies have been performed using SNP genotyping arrays which suffer from low CNV resolution and limited dose response. We have recently developed methods to allow large scale copy number association tests from Exome sequences within the UK Biobank. These methods result in high resolution (exon level) CNV information with good association discovery signal for human traits. We have run copy number association testing for a variety of human traits and have generated robust results verifying some important regions within genes previously known to impact these traits. Furthermore, these analyses have resulted in new findings that have not be described previously but show great promise in terms of, for example, gene function. We are undertaking research involving genetic association testing for SNPs and CNVs in COVID-19 patients using data from the UK Biobank and Genomics England. Our CNV association methods can be scaled up to generate results across extremely large whole Exome and whole Genome sequencing datasets. Importantly, we are able to correlate GWAS findings between these two classes of genetic variation where, in some cases, when certain SNPs can 'well tag' specific CNVs the differences in human trait distributions could be discovered by the two approaches independently. However, there are a large number of CNVs that cannot be well tagged by single or multiple SNPs and it is these associations that would not be found using other approaches. Additionally, the interplay between SNPs and CNVs adds important information into the understanding of human traits and to the genetics of differences in symptom severity seen in covid-19 infection. We are actively developing SNP-CNV imputation methods such that we can built robust imputation models for CNV locations across the genome. This allows us to impute copy number information into further SNP genotyping cohorts worldwide adding considerable value to the global association testing efforts for covid-19. Many groups across the world are actively undertaking genetic research into covid-19 susceptibility using large scale GWAS analysis from SNP genotyping arrays. However, there are far fewer who can quickly and effectively leverage the CNV information available from whole Exome and Genome sequence data to allow genome wide association testing of CNVs. It is clear that differences in copy number can cause big differences in human traits and influence health. CNVs are certain to be one of the genetic sources of differences that we observe across the wide range of responses to covid-19 infection. Results from this project will contribute to an improved understanding of the genetic basis of differences in symptom severity of covid-19 cases. There are likely to be a large number of specific risk factors based on rare variants in the human population that confer an increased risk of severe symptoms. It is unclear whether there will be a single (or small number) of highly significant genetic variants with large effect sizes that predispose individuals to an increased risk of severe symptoms. It is however likely that a large number of rare or combinations of rare and common genetic variants may lower an individual's robustness to covid-19 infection overall. It is entirely possible that commonly observed CNVs may associate with differences in covid-19 symptom seve",2020,2022,EMBL - European Bioinformatics Institute,358623.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C04643,ES/V011138/1,Periods in a Pandemic: how UK period poverty initiatives are managing with Covid-19 related challenges,"Period poverty refers not only to economic hardship with accessing period products, but also to a poverty of education, resources, rights and freedom from stigma for girls and menstruators (1). Since March 2020, and the introduction of lockdown/social distancing measures as a result of the Covid-19 pandemic, more than 1 of every 10 girls (aged 14-21) cannot afford period products and instead must use makeshift products (toilet roll, socks/other fabric, newspaper/paper). Nearly a quarter (22%) of those who can afford products struggle to access them, mostly because they cannot find them in the shops, or because their usual source/s is low on products/closed (2). Community /non-profit initiatives face new challenges related to Covid-19 lockdown measures as they strive to continue to support those experiencing period poverty. Challenges include accessing stocks of period products, distribution of products given lockdown restrictions, availability of staff/volunteer assistance and the emergence of 'new' vulnerable groups. There is an urgent need to capture how initiatives are adapting to challenges, to continue to support the needs of those experiencing period poverty during the pandemic. This data is crucial to informing current practice, shaping policy, developing strategies within the ongoing crisis and any future crises, and ensuring women and girls' voices are centralised. The project builds upon existing limited knowledge by providing insight into how UK based initiatives and projects are mitigating challenges linked to Covid-19, by examining how they are continuing to meet the needs of those experiencing period poverty and identifying any gaps in provision. 1. Montgomery P., et al., 2016. Menstruation and the Cycle of Poverty. PLoS ONE 11(12): e0166122. 2. Plan International UK, 2020. The State of Girls' Rights in the UK: Early insights into the impact of the coronavirus pandemic on girls. London: Plan International UK",2020,-99,Birmingham City University,54723.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04644,ES/V012053/1,Supporting people bereaved during COVID-19: a mixed methods study of bereaved people's experiences and the bereavement services supporting them,"People bereaved during the Covid-19 crisis face significant challenges that shape their experiences of grief. The sudden nature of many Covid-19 deaths and infection control measures that limit family contact with patients adds to the distress of the bereaved. Whether the cause of death is Covid-19 or another illness/event, social distancing measures mean that family members grieve alone and mourning practices are disrupted. People from Black and minority ethnic groups (BAME) are particularly affected by Covid-19 and also experience barriers to accessing bereavement services. Covid-19 has also brought significant challenges for bereavement services. Social distancing requirements make usual in-person individual and group bereavement support impossible, whilst responding to abnormal bereavement requires additional competencies among staff. This study aims to investigate the grief experiences, support needs and use of bereavement support by people bereaved during the pandemic, and the adaptations, challenges and innovation involved in delivering equitable bereavement support. We will use qualitative and quantitative methods in three work packages: Work Package One involves a UK wide survey administered at three time points: baseline, 7 and 13 months post-death. Recruitment will be via social media, organisations representing BAME groups, and bereavement organisations. Questions will investigate the impact of end-of-life and post-death experiences during Covid-19 and subsequent access to, needs for and experiences of bereavement support. Validated measures will assess grief and coping response, social support, prolonged grief disorder (PGD) and quality of life (QoL). Work Package Two involves semi-structured telephone interviews with a selection of survey respondents after each survey round. The interviews will explore experiences of grief and bereavement during Covid-19, including bereavement support use and unmet needs for support. When selecting interview participants, priority will be given to people from BAME backgrounds and those whose survey responses indicate unmet needs, greater vulnerability and poorer outcomes, to enable exploration of specific challenges during the pandemic. Work Package Three will include an online survey of bereavement service providers. The survey will identify service adaptations, key challenges and approaches to delivering accessible bereavement care during the pandemic. Survey findings will inform targeted case studies, developed via telephone interviews, to describe innovative practice. This study, developed with public contributors, will identify 'real-time' implications for the delivery of end-of-life care and bereavement support during and beyond the pandemic. It will enable us to recommend how to achieve equitable and effective bereavement support, pandemic-specific competencies needed by bereavement support workers and specific types of support that should be prioritised at regional and national levels, whilst working throughout to ensure prompt translation into practice.",2020,-99,Cardiff University,463333.17,Human Populations,Asian | Black,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04645,ES/V011855/1,COVID-19 and rough sleepers: a randomised controlled trial to evaluate models of housing and support to reduce infection and homelessness,"As part of the government's response to COVID-19, 15,000 rough sleepers have now been offered self-contained temporary accommodation in England, mainly in hotels. This approach, which has involved the decanting of hostels, shelters and similar shared provision for rough sleepers, is a short-term response. When the lockdown ends, decisions will need to be taken about how to house former rough sleepers in line with the UK government's commitment to prevent people from going back to the streets - including, potentially, through the re-opening of shelter-type accommodation. Existing temporary accommodation with shared facilities might make it impossible for people to comply with government social distancing advice. So these decisions will impact on the risk of a second wave of infection from COVID-19 and possibly any mutations. This proposal outlines a unique time limited opportunity to conduct the first ever randomised controlled trial in the UK, to evaluate the effectiveness and cost-effectiveness of permanent housing on the risk of COVID-19 infection and housing stability for people experiencing homelessness. That many homeless people are currently waiting to be housed means they can be randomly allocated to different housing solutions at scale quickly. The insights drawn from the short-term impacts of permanent housing can be used to inform other local authorities' responses to the challenges of COVID-19 and the cost-effectiveness of accommodation alternatives more broadly.",2020,-99,Cardiff University,718095.27,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts, +C04646,ES/V010026/1,"Modelling the effects of pandemic control measures and financial support on businesses, regions and households","The economic consequences of the COVID-19 pandemic are far from over. Short-term interventions to contain the spread of the virus and its economic fallout are gradually being unwound. Now, as the lockdown is being lifted, attention is rightly turning to questions of which policies will best support firms, businesses and households in the medium to long-run. Over the coming months, the government faces a number of difficult challenges with long run implications, including how to reopen the economy safely, how and when to address its mounting debt burden, and how to ensure a sustainable economic recovery. We propose two complementary, interlinked strands of research that will help the government navigate these challenges. The first strand will build a sectoral-regional model of the economy. Our detailed model will incorporate several novel features that will allow to assess the impacts of very specific policy interventions, including financial support targeted to different industries, and relaxing or re-imposing social distancing restrictions in different areas. This will provide real-time, practical guidance to policymakers on the short and long-run impacts of different policies on output, investment, and employment in different sectors and regions of the UK. The second strand of work will estimate a model of consumer behaviour to understand the effects of lockdown on households' spending decisions and living standards. This will allow to understand how spending patterns change in response to lockdown measures and price changes, and how restricting the availability of goods affects household living standards (including differences across the income distribution).",2020,-99,Institute for Fiscal Studies,160939.11,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C04647,AH/V008412/1,Sharing Good Practices in Protection of Workers and Victims of Modern Slavery During the COVID-19 Pandemic,"The main objective of this project is to conduct evidence-based research on the key impacts of COVID-19 on modern slavery and identify/share good practices in protecting workers and victims of modern slavery in order to facilitate a victim-centred approach. The pandemic has posed unprecedented challenges to the protection and promotion of human rights, and its impact on modern slavery is no exception. For instance, it has made a large number of workers across the world unemployed because of the closure of businesses, and this may be encouraging them to seek employment in informal or even illegal economies which are rife with exploitation. For those businesses which have seen an increase in the labour demand (such as agriculture, food production/processing, and manufacturing of medicines and medical equipment), the pandemic may give strong incentive for them to exploit vulnerable individuals. In addition, States are shifting their resources to fighting the pandemic, with the result that anti-slavery efforts may be undermined and those already caught in slavery, forced labour and other slave-like practices are left unidentified and unprotected. At this moment, however, actual impacts are yet to be examined thoroughly as the situation is still evolving and things remain speculative, leaving a number of important questions. For instance, the extent to which unemployment is actually pushing people into slavery and forced labour is not entirely clear. Also, while an increase in demand for labour in certain sectors may give strong incentives for businesses to exploit vulnerable individuals, a clear global trend is yet to be established in this regard. In addition, a question remains as to how the reallocation of States' resources from anti-slavery efforts is contributing to further victimisation of people already held in slavery and forced labour. Finally, there are additional questions in relation to protection measures: Do they address the key impacts of COVID-19 sufficiently? Is protection tailored to address the specific needs of particularly vulnerable populations such as women, children and young people and minorities? Can they be accessed by all workers without discrimination? What are practical difficulties in implementing them? The project aims to answer these questions and fill the existing knowledge gaps. The team will conduct research on the key impacts of the pandemic on modern slavery. It will then identify and assess the appropriateness and effectiveness of measures designed to protect workers and victims of modern slavery with a view to sharing them widely among relevant governmental, civil society, inter-governmental and private stakeholders. Finally, in order to promote a victim centred approach, the team will create ""Guiding Principles on Actions against Modern Slavery during the State of Emergency"" containing important human rights norms and principles to be upheld by governmental and non-governmental stakeholders. In terms of research methods, the team will employ desktop research of materials already available in public domain, such as reports and literature published by scholars, governments, NGOs, international organisations and other stakeholders. This will be complemented by virtual interviews to be conducted with stakeholders located around the world, allowing the team to triangulate and verify desktop research. At the end of the project, a project report containing an analysis of the impacts of COVID-19 on modern slavery, good practices in protection of workers and victims of modern slavery, and the Guiding Principles on Actions against Modern Slavery during the State of Emergency, will be produced. The report will be launched at dissemination events in London and Geneva, and team will also promote long-term impact through knowledge transfer and public engagement globall",2020,-99,Keele University,80868.81,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C04648,ESRCCOVID101,The fiscal response to Covid-19: 'Thinking big' on tax policy after the crisis,"Covid-19 is placing extraordinary pressure on public finances. The short- and long-term responses to the crisis will need to be matched by a transformative fiscal settlement for the UK. So far, there has been a lack of 'big thinking' on tax policy to match the scale of this challenge. Reforms to existing taxes are necessary, but may be insufficient._x005F_x000D_ This project convenes a network of world-leading tax experts to provide rapid-response evidence and recommendations to government on the case for introducing a new 'wealth tax' for the UK. Unlike many other OECD countries, the UK has never had a wealth tax; the last time this policy was seriously considered was in 1974._x005F_x000D_ The project will ensure that this policy option is 'on the table' in upcoming fiscal debates about the national recovery from Covid-19, by:_x005F_x000D_ WP1: Creating an evidence base - we have already commissioned eleven 'evidence papers' on key principles and design issues. These papers will provide a detailed and robust new evidence-base that can be used directly by officials at HM Treasury and HMRC._x005F_x000D_ WP2: Modelling revenue and distributional impacts - we are using state-of-the-art quantitative methods and the best-available data sources to model how much revenue a wealth tax could raise, and its impact on the distribution of wealth, based on a range of policy options._x005F_x000D_ WP3: Providing policy recommendations - we will publish a final report summarising our conclusions on the feasibility and design of a new wealth tax for the UK, including (if appropriate) a fully-costed 'ready to legislate' proposal._x005F_x000D_ If funded, we will deliver all of these work packages - including the final report - by December 2020, in time to feed into the Budget and associated fiscal debates occuring in Spring 2021.",2020,-99,London School of Economics and Political Science,128094.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C04649,ES/V010433/1,Generation COVID and Social Mobility: Evidence and Policy,"Our aim is to provide a comprehensive picture of the challenges the pandemic presents in terms of fostering a more socially mobile society in absolute and relative terms. Young people who fall into low quality jobs, long-term unemployment, or who fail to achieve the exam grades needed to pursue the next steps in education, training or employment, are unlikely to rise above the economic status of their parents during their lifetime. They face the prospect of faring worse than previous generations. Our focus is on these aspects of young people's lives and, in particular, on how policy can prevent an even greater chasm opening between the 'haves' and the 'have nots' by preventing educational and labour market 'scarring' of the hardest hit members of the COVID-19 generation. The starting point of the empirical analysis is to show how children's educational environment has been affected by the pandemic and how opportunities for learning from home differ by socioeconomic status. We will document how differences across individuals in parental time inputs, monetary inputs (such as online tutoring), and access to online schooling resources, differ by socioeconomic background. We will also explore how parental job loss and labour market status have shaped the home learning environment. Parents facing financial hardship, greater stresses caused by failing health, or increased workload due to having key worker status, are unlikely to be able to provide as much time and support for their children as higher earning parents who are able to work from home. We aim to quantify how these inputs combine to produce marketable skills and discuss policies to remedy the falls in inputs and ensure that the talent of children who have missed out on key instruction time does not go unfulfilled. Economic and educational hardship go hand in hand. Failing to reach one's potential at school can close the door not only to higher education, but also to the most desirable jobs and early career training opportunities. A dearth of opportunities early on can lead to limited opportunities later in life. In addition to education, we will focus on how the pandemic has affected those entering the labour market and those early in their careers. Given our focus on social mobility, we will look at how individuals from different backgrounds have had different labour market outcomes during lockdown. We will discuss what these outcomes are likely to mean for individuals as the lockdown ends and the transition towards a functioning labour market begins. Once again, we will present a series of proposals, and assess their efficacy, in light of our findings. The policy proposals are aimed at preventing current economic inequalities being further exacerbated by COVID-19. In particular, we will consider evidence (of our own and from others) to look at policies surrounding school and university admissions, vocational training and reskilling, and more general labour market policies such as job guarantees. In order to carry out the above, we will make use of a range of datasets that follow young people as they age. These data allow us to link home environments with labour market outcomes for birth cohorts. The three datasets that we will use - Understanding Society, the Millennium Cohort Study, and Next Steps - also contain, or will contain, modules looking at how the Covid-19 pandemic has affected study participants. In order to gauge the extent to which the polices we propose are supported by the public, we will also carry out a survey asking participants of their views on the redistributive polices that we propose.",2020,-99,London School of Economics and Political Science,355482.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C04650,ES/V010182/1,Enhancing the use of ResilienceDirect in the Covid-19 response: a comparative analysis of Local Resilience Forums,"The project will explore and enhance how the ResilienceDirect (RD) digital collaboration platform is used by multi-agency Local Resilience Forums (LRFs) to remotely plan and respond to the COVID-19 pandemic. LRFs are an integral component of the COVID-19 response as they enable multiple local (e.g. police, NHS, local authorities) and national agencies (e.g. Public Health England, Environment Agency) to work with central government departments to develop shared situational awareness, joint decision-making and collaborative forms of learning and knowledge sharing. They provide a vital function to enable an integrated emergency response as multi-agency co-ordination failures have often weakened previous emergency responses. During the COVID-19 response, the requirement for remote working means this collaboration is to a greater extent occurring digitally within the RD digital platform, produced by the Cabinet Office. Given the scale and complexity of COVID-19 response, the challenge of multi-agency working, and the shift toward digital collaboration, it is vital that LRFs fully understand how to overcome significant potential barriers in how multiple agencies can work together within and between LRFs. The project will explore two key barriers within and between LRFs. First, within LRFs, although RD can enable rapid information sharing and decision-making, if RD does not align with the interests of multiple LRF user agencies it can generate barriers to their collaboration. The project will examine how RD enhances or undermines collaboration between LRF agencies by exploring the interaction between the various human and technological actors that deliver digital collaboration. Second, between LRFs, it is well known that different LRFs organise their responses on RD differently but no evidences exists as to why these differences exist or their outcomes. Further, these differences generate significant opportunities for learning in the dynamics of digital collaboration yet that learning remains tacit and not shared. This project will render this learning accessible between LRFs by comparing and explaining the differences and similarities between how LRFs use RD to enable collaboration. This analysis will then inform 'best practice' proposals in digital collaboration which will be shared and refined with LRF users through the 'Learning and Development' section of RD. By exploring digital collaboration during the COVID-19 response, the research will produce the first independent evidence base for LRF practitioners, national policymakers, and scholars, to understand how RD is being used to facilitate LRF collaboration. This research will provide timely, cyclical feedback on the effective use of RD to support multi-agency collaboration. This project is designed to deliver immediate impact to improve the strength of the UK's integrated response to COVID-19 as well as critical insights into the role of digital technology in facilitating emergency collaborations that will benefit future responses.",2020,-99,Loughborough University,140465.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems | Health leadership and governance, +C04651,CONDOR/MC_PC_20008,COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR),"In response to the COVID-19 pandemic, multiple in vitro diagnostics tests (IVDs) have been rapidly developed to detect SARS-CoV-2 infection or immunity. To meet the urgent demand for increased testing capacity, many IVDs have received emergency use authorization. However, clinical evaluations to date have mainly been single-centre, employing differing reference standards with variable protocols. There remains an urgent need for a multi-site, rapid,and methodologically robust approach to in-context clinical validation. CONDOR will contribute to the coordinated national effort to improve COVID-19 diagnostics by providing a collaborative national platform for clinical evaluation. Incorporating community, care home and in-hospital prospective multi-centre studies, CONDOR will provide in-context clinical validation for multiple IVDs, specifically applied to high-priority use cases. This collaborative platform will also place the UK in a unique position to rapidly evaluate and adopt novel diagnostics into clinical practice when faced with future pandemics. The platform has 4 main elements: 1) A central steering committee to create bespoke evaluation plans for Serology Task Force and VDTAG Priority novel IVDs and their associated use cases. 2) In context laboratory verification via a laboratory network. 3) Evaluation of in-context clinical performance (diagnostic accuracy) of IVDs (self-tests, POCTs and laboratory platforms) through efficient, prospective, multi-centre studies using established clinical networks. 4) Cross-cutting methodological workstreams. a. Care pathway analysis informing use case and TPP development (led by DHSC, RCPath and MHRA) and evidence framework development (in collaboration with NICE). b. Evaluating utility and usability in laboratory and clinical settings.",2020,2022,"Manchester University NHS Foundation Trust, University of Oxford",757673.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C04652,BB/V01126X/1,"Assessing SARS-CoV-2 entry, replication and prevention in a primary human conjunctival cell model and organ cultured cornea/conjunctiva.","The SARS-CoV-2 virus, which has caused the COVID-19 pandemic, is highly infectious and predominantly transmitted through respiratory droplets. To enter the host cell SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a cellular receptor and the transmembrane protease serine type 2 (TMPRSS2) for fusion of viral and cellular membranes. The ocular surface epithelia, conjunctiva and cornea, represent an additional mucosal surface, which can be exposed to respiratory droplets. Several published reports have shown that SARS-CoV-2 can cause conjunctivitis, either as an early sign of infection, or during hospitalization for severe COVID-19 disease. In a recent study of 38 COVID-19 patients, 31.6% had conjunctivitis with 16.7% of these testing positive for SARS-CoV-2 from conjunctival and nasopharyngeal swabs. There is evidence that numerous properties allow the eye to serve as a potential site of virus replication and a gateway for the establishment of respiratory infection, through the nasolacrimal system linking the ocular and respiratory tissues. Our recent data shows co-expression of ACE2 and TMPRSS2 in human superficial conjunctival, limbal and corneal epithelium, suggesting a potential extra-respiratory transmission route of SARS-CoV-2 via the ocular surface. In this proposal we will use human ex vivo differentiated conjunctival and corneal epithelium and organ cultured cornea/conjunctiva as pre-clinical tools to study the entry of SARS-CoV-2 via the ocular surface and to develop effective diagnostic, prophylactics and treatments in the fight against COVID-19. We envisage that proof-of-concept studies developed herein will lead not only to development of eye drops, but also nasal sprays and mouth washes, to provide the much-needed therapies in time of pandemics.",2020,-99,Newcastle University,249480.84,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04653,BB/V006584/1,Development of a highly sensitive serological assay for Covid-19 based on the use of virus-like particles and protein-based nanoparticles.,"Clinical studies have reported co-infections in at least 20% of Covid-19 patients. This figure is likely underestimated because ICU mechanical ventilation results in up to 75% of patients developing nosocomial pneumonia. Moreover, pathological analysis of post-mortem biopsies of lung from patients who died of severe COVID-19 revealed histopathologic findings consistent with superimposed bacterial pneumonia in some patients. Alarmingly, this occurs in a scenario of a limited arsenal of antibiotics to target these infections.Nothing is known on the effect of co-infections in SARS-CoV-2-induced pathophysiology. It is also unknown whether SARS-CoV-2 infection may affect the pathophysiology of nosocomial infections. Addressing this knowledge gap is critical if we are to develop therapeutics; otherwise, treatments may tip the balance from one infection to the other. This happens in a scenario of a limited arsenal of antibiotics to target nosocomial infections. We will investigate the interface between SARS-CoV-2 and bacterial infections (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) by exploiting relevant translational research models: well-differentiated primary human airway epithelial cell cultures (WD-PAECs), excellent surrogates of human airway epithelium in vivo, and PBMCs, reflecting the complexity of the human immune system. Single-cell RNA seq and multiplexed single-cell mass cytometry (CyTOF) will reveal cell-type specific immune pathways associated with the infections. These responses might be suitable for therapeutic manipulation. Cytopathogenesis, viral and bacterial replication in co-infection, and cytokines/chemokines will be additional read-outs. The effect of SARS-CoV-2 and bacteria on each other's virulence will be analysed by determining the transcriptome of exposed bacteria, and investigating viral and bacterial infection parameters upon infection of WD-PAECs and PMBCs. We will screen a panel of FDA-approved drugs affecting host-pathogen interactions to identify drugs against SARS-CoV-2 in the co-infection interface. These drugs shall be considered as new therapeutics entering clinical trials.",2020,-99,Queen's University of Belfast,619963.68,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies", +C04654,EP/V026054/1,Social Protection and the Gendered Impacts of COVID-19 in Cambodia: Longitudinal Research to 'Build Back Better' in the Global Garment Industry,"The COVID-19 pandemic is having significant repercussions on the global garment industry, of huge importance not only to Cambodia's economy, but also to its 1 million workers, 80% of whom are women. Many garment factories are interrupting production with the effect that 1/4 of workers have been dismissed or temporarily suspended. Formal social protection in the sector, though improving due to multi-stakeholder efforts, is weak and fragile. Mixed-method longitudinal research will track and amplify the experiences and coping mechanisms of 200 women workers as they navigate the financial repercussions of the COVID-19 pandemic. The project's interdisciplinary team from human geography, political economy, and organisation studies will generate new knowledge on underlying and differentiating determinants of risk and resilience arising from formal and informal social protections. The ambitious study will focus its policy attention on learning to 'Build Back Better' social protection to prevent and mitigate longer-term impacts of the pandemic and future risk events. Our approach centres women's representation in planning and decision-making as critical to 'stitching back better' just and resilient garment supply chains to make progress towards gender equality (SDG5), inclusive economic growth and decent work (SDG8). The project's impact, within its 18-month lifetime, will be compelled by its partnerships with, and pro-active convening together, of government (Cambodian Ministry of Labor, British Embassy), regulators (ILO, Better Factories Cambodia), industry (Garment Manufacturers Association in Cambodia, H&M), think tanks (ODI), workers' organisations (CATU, the only female-led union in Cambodia), and women's media (Women's Media Center and the Messenger Band).",2020,2022,Royal Holloway University of London,231347.31,Human Populations,Asian,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | Western Pacific,Gender,,,United Kingdom,United Kingdom | Cambodia,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C04655,BB/V006576/1,"COVID-19: role of co-infections, and drug repurposing for treament","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic of COVID-19. Our lack of understanding about the pathogenesis of SARS-CoV-2 in the human airways is an important barrier to developing effective treatment strategies for COVID-19. So far, we know that COVID-19 disease severity increases with age, with very few severe cases among children. In China, the case fatality ratio was 60-year olds, rising to 15% in those >80. This project will focus on two aspects of the host response of infection, studying how the cells that line the airway respond to the virus, and whether the recruited immune cells (focussing on the behaviour of neutrophils that are the first to respond to infection) the help reduce viral load or contribute to airway damage and the build-up of debris in the airways. We will use an experimental SARS-CoV-2 infection model of the airway epithelium from young children, adults and the elderly. Our objectives are to determine: 1) if the primary site of infection - the nasal epithelium - of the elderly exhibit increased viral replication and increased inflammatory response to SARS-CoV-2 infection compared to children. 2) the molecular mechanisms that govern age-determinants of COVID-19 disease severity using single-cell genomic analysis of cultured cells and comparing outputs to the same data from age-matched COVID-19 patients using scRNAseq. 3) whether the innate immune response to SARS-CoV2 infected airway epithelium exacerbates inflammation and contributes to the severity of illness in the elderly by measuring a) the intensity of immune cell (neutrophil) recruitment to the airway b) epithelial damage and c) neutrophil phenotype and function. It is important that we understand the reasons for these fundamental differences in responses in order to help determine what the most appropriate therapy is for COVID-19 disease in these age groups. There is much debate about the utility of novel and exsiting anti-virals as well as immune modulator therapies including NSAIDs and Tocilizumab. This project will rapidly deliver new understanding about the viral pathogenesis and the cause of these age-related disparties in disease outcomes. Not only will this help support the development of effective therapeutics in the short-term, underlining the relevance of this model for the preclinical evaluation of antiviral candidates, but it may also highlight important risk factors or protective mechanisms that could be used to develop early interventional or prophylaxtic therapies in the long-term.",2020,-99,University College London,490393.5,Other,Unspecified,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity | Disease pathogenesis", +C04656,ES/V011103/1,"The Economic, Social, and Cultural impact of the COVID-19 Pandemic on Independent Arts Workers in the United Kingdom","COVID-19 threatens the performing arts; closures of theatres and outlawing of public gatherings have proven financially devastating to the industry across the United Kingdom and, indeed, the world. The pandemic has sparked a wide range of industry-led strategies designed to alleviate financial consequences and improve audience capture amidst social distancing. COVID-19 has affected all levels of the sector but poses an existential threat to freelancers--Independent Arts Workers (IAWs)--who make up 60% of industry workforce in the UK (EU Labour Force Survey 2017). The crisis has put a spotlight on the vulnerable working conditions, economic sustainability, mental wellbeing, and community support networks of IAWs. IAWs are often overlooked by the industry and researchers, however it is their very precarity that makes them pioneers of adaptability responsible for key innovation within the sector. IAWs may prove essential for the industry's regrowth post-COVID-19. An investigation is necessary into the impact of COVID-19 on IAWs and the wide-ranging creative solutions developing within the industry to overcome them. There has been increasing pressure to gather 'robust, real-time data' to investigate the financial, cultural, and social potential long-term consequences of COVID-19 on the UK theatre industry. The impact of the pandemic on IAWs is particularly complex and wide-ranging. A TRG Arts survey stated that 60% of IAWs predict their income will 'more than halve in 2020' while 50% have had 100% of their work cancelled. Industry researchers from TRG Arts and Theatres Trust have launched investigations examining the financial impact of COVID-19 on commercial venues and National Portfolio Organisations, but there has been insufficient research into the consequences for IAWs (eg. actors, directors, producers, writers, theatre makers, technicians) and the smaller SMEs beyond income loss and project cancellation data. In May 2020, Vicky Featherstone of the Royal Court Theatre, stated the importance of support for the 'massive freelance and self-employed workforce' she believed has been 'taken for granted' by the industry. Our study fills this gap by capturing and analysing not only the economic impact, but the social and cultural transformations caused by COVID-19 by and for IAWs. We will compare regional responses across England, Wales, Northern Ireland and Scotland as well as variations across racial and socio-economic groups. Our aims are to document and investigate the impact of COVID-19 on IAWs, identify inequalities in the sector, investigate changes in the type of work produced post-COVID-19, and help develop strategies for how the sector can move forward from this crisis. We will investigate connections between the financial consequences of COVID-19 and creative strategies for industry survival including social support networks, communication initiatives between arts venues and IAWs, and the development of mixed-media work in the wake of the pandemic. Our study scrutinizes the economic, cultural, and social impact of COVID-19 on IAWs and the organisations that serve them with the aim of informing strategies for sector recovery.",2020,-99,University of Essex,509058.51,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C04657,AH/V008102/1,Digital Theatre Transformation: A Case Study and Digital Toolkit for Small to Mid-Scale Theatres in England,"This project aims to provide a roadmap for local and regional companies that will enable them to bring furloughed staff back onto their payroll and develop new ways of working, in terms of administration and creative output, that are less building-dependent and that enable flexible modes of working to mitigate the impacts of Covid-19 on local and regional theatres. The project investigates and learns the lessons from the success of Creation Theatre (Oxford), together with Big Telly (Northern Ireland) in rapidly transforming their business model and theatre practice from local/regional face-to-face immersive location-based performance to a distributed home-working model that brings the interactive and immersive elements of their theatre work online through the Zoom platform, with a national and even international reach. Through a quantitative analysis of existing digital audience datasets, supplemented by new qualitative questionnaires and audience interviews, the project explores the impact of Creation Theatre's Zoom production of The Tempest on its audiences and its ability to impart digital skillsets along with a sense of well-being and community. A comparative analysis of audience responses to pre-recorded and live performances will furthermore answer vital questions about the relative commercial value of the live experience. The outcomes of this research will rapidly be published and disseminated through professional associations. Working with representatives of Equity (UK trade union for creative practitioners), our team will moreover develop guidelines for digital home-working that take account of the technical and ethical impacts of the change in working practices and environments on staff.",2020,-99,University of Exeter,64009.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C04658,EP/V026038/1,Improving COVID-19 and pandemic preparedness and response through the downstream of multi-hazard early warning system,"Many countries are now suffering after years of insufficient attention to warnings about the need for improved pandemic preparedness. The WHO has declared COVID-19 a pandemic, but its underlying factors, vulnerabilities and impacts go far beyond the health sector, and in Sri Lanka, it is overwhelming government and response agencies. This study will address two, inter-related challenges: How will countries cope if a major natural hazard occurs while the COVID-19 pandemic is ongoing? How can pandemic preparedness make use of the existing infrastructure for tackling other hazards? The project team will attempt to understand the potential impact of a pandemic-natural hazard hybrid scenario. It will also seek to improve early warning and preparedness for such an event, as well as the availability of and access to multi-hazard early warning systems (MHEW) and disaster risk information that include pandemic/biological hazards, which is also Target G of the SFDRR [1]. We will address these challenges by examining how public health actors be better included within a MHEW environment and how pandemic threats are integrated within national and local DRR strategies. We will explore the impact of COVID-19 on the response capabilities for other hazards, either multiple simultaneous events, or cascading impacts, and consider how COVID-19 and public health surveillance can be synergised with ""the last mile"" of MHEW. Pandemic is global, but the preparedness and response is local, and that response is very dependent on governance, laws, culture, risk perception and citizen behaviour. The study has been designed in close collaboration with Sri Lankan health and DRR agencies who identified the key gaps that need exploring. The team will develop and disseminate guidance to better incorporate pandemics and other biological hazards into national and local DRR preparedness and response",2020,2022,University of Huddersfield,156945.27,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,United Kingdom | Sri Lanka,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C04659,AH/V00820X/1,When pandemic and everyday ethics collide: supporting ethical decision-making in maternity care and paediatrics during the Covid-19 pandemic,"The response to Covid 19 (C19) will have far reaching consequences for the NHS. This project focuses on how this response has created significant ethical issues for providers of non-C19 services when deciding how to prioritise and reconfigure services. Our central aim is to evaluate and support ethical decision-making in two non-C19 areas: maternity and paediatrics. We have chosen these areas because they have been significantly affected by the C19 response, with professional and patient organisations highlighting the problematic effects on both areas (First 1001 Days, Royal College of Midwives, Make Births Better). Objectives 1. Conduct a rapid review of current local policies and policy-making processes for non-C19 maternity and paediatric services. 2. Examine how the policies are applied in clinical practice and pilot test approaches to ethics support. 3. Make recommendations for ethics support at local policy-making and practitioner levels; and develop tools to support good decision-making practice. This inter-disciplinary project is an empirically informed ethical analysis of current policies, processes and practice in non-C19 maternity and paediatrics. Design: empirical ethics, employing Frith's symbiotic empirical ethics approach, where philosophical theory is used to explore the data, draw normative conclusions, and make policy and practice recommendations. Methods: rapid review of local policies and decision-making processes; analysis (against the national ethics framework for pandemics) of the values being engaged; interviews with key stakeholders involved in policy formation, and healthcare practitioners to understand how the policies are being applied in clinical practice and what support they might need in their ethical decision-making.",2020,-99,University of Liverpool,331185.57,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Research to inform ethical issues | Health Systems Research,"Supportive care, processes of care and management | Research to inform ethical issues in Clinical and Health System Decision-Making | Health service delivery", +C04660,ES/V011154/1,"COVID-19 Risk and Response: Impacts and Mitigations for Modern Slavery Victims, Survivors and Vulnerable Populations","As the UN explained on May 5, COVID-19 ""is likely to increase the scourge of modern-day slavery."" Victims and survivors of modern slavery are at greater risk of ongoing exploitation and re-exploitation. Traffickers will increase recruitment and seek to maintain revenue during economic crisis. Victim identification has become even more challenging as States shift protection resources towards combatting the pandemic. Access to shelters is increasingly limited, and provisions in the 2015 Modern Slavery Act on victim support may be compromised. Economic contraction and resource reallocation will undermine the anti-slavery work of third-sector organisations, law enforcement and local government. NHS staff are stretched to capacity and may not recognise victims. We respond to many warnings by the policy community that, as the UN noted, ""inaction could lead to a sharp rise in the number of people being pushed into slavery"" because of COVID-19. Elsewhere the UN has called upon governments to ""urgently adopt inclusive measures aimed at protecting...trafficked persons in their national response to COVID-19,"" calling such measures ""urgent and necessary."" The OSCE has declared that the crisis brings an acute ""obligation to combat the exploitation of vulnerable people"" and that combating slavery during COVID-19 is ""an urgent priority."" A consortium of NGOs has warned that COVID-19 will have similar consequences to natural disasters, causing spikes in slavery. Yet while there is an increasing number of risks being articulated across the anti-slavery sector, they are not being gathered and assessed in a robust, coherent way. There is no attempt underway to complete a full COVID-19 risk/response assessment for slavery victims/survivors in the UK, although UK-based organisations are sharing their immediate challenges. As we do not fully understand the risks, governments and third-sector organisations cannot effectively respond to calls-including those from the UN-for the urgent adoption of protection and mitigation measures. The complexity of the risk environment may impede anti-slavery mitigation unless risks can be assessed. We need to analyse risk and recommend mitigation, in order to ensure that COVID-19 does not increase enslavement and jeopardise slavery survivors' recovery. We therefore answer the question: what are the accrued risks and mitigating responses of COVID-19 for victims and survivors of slavery? To answer this key question, we answer the sub-questions: What are the causal pathways throughout which mitigations are expected to work? Do these efforts reflect survivors' experiences? We systematically analyse risks and responses across a year, in order to provide large-scale evidence and best-practice recommendations. We do not duplicate the valuable risk mitigation work of front-line organisations, but support it with state-of-the-art risk assessment, using survivor insights and real-time data, for the sector's direct use. Derived from disaster response techniques and public health frameworks, our participatory risk assessment includes interview, survey and web-monitoring data. Our multi-method design includes qualitative and quantitative surveys, public information monitoring, a modified e-Delphi, evidence reviews, and risk analysis. We adopt a multi-level approach to consider risk and assess against a framework adapted from our social determinants model. As we assess risk, we analyse responses and recommend mitigations. To provide lessons, this includes comparative analyses of responses by other countries and during other disasters.",2020,-99,University of Nottingham,515943.24,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04661,ES/V011081/1,Homelessness during the COVID-19 pandemic: homeless migrants in a global crisis,"People experiencing homelessness are disproportionately impacted by the coronavirus. This project, involving researchers from University of Portsmouth, University of Sussex and St Mungo's, the homelessness charity, will produce an 18-month qualitative-based study of migrant homelessness during the crisis. A particular focus of the study will be the experience of non-UK nationals. Government efforts have helped provide emergency accommodation for thousands of homeless people during the crisis, but concerns remain about how homeless migrants with No Recourse to Public Funds (NRPF) can be supported in the longer-term. Many homeless migrants face multiple everyday challenges; they experience the hostility and aggression directed toward homeless people, compounded with often intense experiences of racism. A cultural miasma of fear and anxiety due to pandemic can affect such vulnerable minority groups particularly forcefully. Our project will innovate by examining the biographical and life history narratives of St Mungo's clients in relation to their experiences of homelessness during the coronavirus crisis. In doing so, we will examine the intersection of personal histories, wider social structures and the dynamics of the particular situation. While much of the research on homelessness is nationally specific, we will examine the crisis with a global perspective, one that identifies the complex global processes that underpin homelessness as well as the coronavirus. Based on its findings, and working with St Mungo's partners, the project will make recommendations for measures that can be taken across the UK and elsewhere to support migrant groups facing homelessness, during times of crisis and beyond.",2020,-99,University of Portsmouth,197736.36,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04662,ES/V013009/1,"COVID-19: TOURISM RECOVERY, RISK AND UNCERTAINTY","Tourism has been severely affected by Covid-19, and it is anticipated that it will be one of the last sectors to recover fully from the effects of the pandemic. It faces enduring tourist unwillingness to take risks when booking holidays in the face of uncertain health hazards and border/containment controls. Official estimates predict that international tourism will decline by 55% and domestic tourism by 24% in 2020, with demand remaining subdued until 2022. This matters because tourism accounts for almost 10% of UK jobs, dominates some local economies and contributes to the quality of life of individuals. This project will analyze how unprecedented Covid-19 related risks and uncertainties shape tourist intentions in the UK's inbound, outbound and domestic markets: substitution between domestic and outbound (international) tourism will also be analysed. The impacts on different market segments will be examined: on long-haul versus short-haul international tourism, and on urban versus rural versus coastal tourism destinations. Additionally, both attitudes to risk and uncertainty, and vulnerability to Covid-19, also vary by social characteristics: by age, gender, education, income and ethnicity. The research has two main stages. The first analyses large scale surveys of potential tourists in the UK and its four largest markets: Germany, France, USA, and China. Statistical modelling will provide detailed analyses of attitudes to risks and uncertainties in different elements of the tourism experience: travel versus accommodation versus visiting attractions and places of entertainment. The project will also provide an overall assessment of the determinants of tourism intentions in both the short (3 month) and the long term (to the end of 2021). The second stage of the research analyses how individual tourist intentions would change when faced with contrasting Covid-19 health and containment scenarios. How would different types of tourists respond to continuing gradual relaxation of border and social controls as the pandemic retreats, versus a second wave leading to selective or widespread imposition of lockdown controls such as quarantine, border testing, strict social distancing rules, and closure of commercial and social venues. This research will provide a new evidence base on tourist intentions that can underpin more accurate demand forecasts, and more targeted market research and policy measures for UK tourism. The project is undertaken in collaboration with two leading tourism organizations: VisitBritain and the Association of British Travel Agents.",2020,-99,University of Surrey,226178.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe | Western Pacific,,,,United Kingdom,United Kingdom | Germany | France | United States of America | China,"Secondary impacts of disease, response & control measures",Economic impacts, +C04663,EP/V025899/1,COVID-19: Optimal Lockdown,"The current COVID-19 pandemic has caused whole countries to lockdown, with a huge effect on people's lives and in the economy. Naturally, there are questions about how efficient this lockdown is, and increasing interest in how our country will reduce social distancing measures and eventually go back to normal. We propose to answer some of these questions by using cutting edge epidemiological models for the spread of COVID-19 in the UK using census data to model the typical behaviour of the UK population accurately and then combining this with the increasingly available data from the NHS, PHE and the ONS, which will help us model the spread of COVID-19 in our communities. These models will then be explored in order to design an optimal mitigation strategy based on closing public and commercial venues, or shutting down transport links, and an exit strategy from our lockdown, which will be achieved by reopening such venues or gradually restoring public transports. These strategies will be adapted frequently in response to daily data. Our resulting models and control strategy will be publicly available on a dedicated website, which will be updated frequently as new data becomes available.",2020,-99,University of Warwick,261272.73,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Impact/ effectiveness of control measures, +C04664,Additional funding for Vaccines Manufacturing and Innovation Centre,Vaccines Development & Manufacturing Centre - Challenge Fund (MMIC and VDMC),,2020,2022,Vaccines Manufacturing and Innovation Centre UK Ltd,205253190,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2018 +C04665,C19-IUC-033,An app-based solution for remote cognitive and behavioural assessment,An app-based solution providing an efficient way to asses patients prior to online appointments for remote cognitive and behavioural assessment at large scale in remote clinics. It is also useful for providing assessment prior to face-to-face appointments. MHRA approval would make the technology widely available in remote clinics at national level.,2020,-99,UK Dementia Research Institute,,Other,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management", +C04666,C19-IUC-037,Candidate therapeutics R&D - Arresting Coronavirus replication using a microRNA approach,"Arresting coronavirus replication using a microRNA approach, by devising and testing a microRNA/adenoviral vector-based strategy to treat COVID-19 infection by knocking down the orf1ab gene encoding the RNA-dependent RNA polymerase that SARS-CoV-2 uses to replicate.",2020,-99,UK Dementia Research Institute,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C04667,C19-IUC-044,"Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD)","Amendment to an existing UK-wide observational study of stroke and its cognitive and neuropsychiatric complications R4VaD, (as a high risk population for vascular dementia) to collect data on the impact of COVID-19 on stroke patients with vascular disease. These patients have higher risk of catching and having severe COVID disease, are often on ACE inhibitors which may affect their risk. Neurological complications have been reported in a third of COVID-19 infected patients, and patients already in R4VaD follow-up are reporting high levels of anxiety. All ethics, HRA and NRS approvals are in place; recruitment has commenced where resource is available.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C04668,C19-IUC-045,Understanding and manipulating innate-like B cell mechanisms to prevent stroke associated Infection,"Amendment to an existing study - awaiting approval to add a COVID arm to MRC-funded stroke cohort that recently finished recruiting. This cohort has undergone deep immunophenotyping early after stroke to understand stroke-induced immune changes, infection risk, and associations with long-term outcome (including cognition). Project has potential implications for informing patient management prioritisation.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences, +C04669,C19-IUC-057,Covid-19 Cohort Survey (NSHD),"The National Survey of Health and Development (NSHD), run by the MRC Unit for Lifelong Health and Ageing, is providing researchers access to data about how the COVID-19 pandemic has affected over 18,000 participants part of a collaborative consortium of the five nationally representative longitudinal cohort studies based at UCL. The new data will help researchers understand the economic, health and social consequences of the coronavirus outbreak and track the lasting impact on people's lives. For more information, see https://cls.ucl.ac.uk/covid-19-data-from-five-national-longitudinal-cohort-studies-now-available/",2020,-99,MRC Unit for Lifelong Health and Ageing at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts, +C04670,C19-IUC-063,Impact of viral infection on pregnancy,"We have established a wulti-centred programme to study the impact of viral infection on pregnancy and the influence of treatment. In collaboration with the Edinburgh Reproductive Tissue Biobank (ERTBB) researchers will collect clinical information and biological samples from women with suspected and confirmed Covid-19 infection during pregnancy and their babies. This information will be used to assess the maternal responses to COVID-19 infection across gestation and stratify risk of severe disease. The overall aim is to determine the impact of infection on pregnant women asking whether they are more susceptible, maternal to foetal infection, impact on placental function and outcomes of pregnancy.",2020,-99,MRC Centre for Reproductive Health at the University of Edinburgh,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C04671,C19-IUC-070,The impact of COVID-19 on individuals with lived experience of mental illness.,An online survey to assess the mental health impact of the COVID-10 pandemic on those with experience of previous mental illness. Survey page: https://www.ncmh.info/help-with-research/covid-19-survey/,2020,-99,MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04672,C19-IUC-095,CORONAGENES - Genetic variation and Covid symptoms,CORONAGENES - Investigating the link between genetic variation and COVID-19 symptoms using a self-reporting system via an app and individuals with commerical genotyping or linked to existing genotyped cohorts.,2020,-99,University of Edinburgh,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C04673,C19-IUC-097,COVID infection and chronic fatigue syndrome,"Investigating the link between COVID-19 infection and chronic fatigue syndrome, recruiting patients with the syndrome and using the UKBB cohort to look for genetic determinants of post viral fatigue-like symptom severity",2020,-99,University of Edinburgh,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences, +C04674,C19-IUC-098,SARS-CoV-2 serology test,"Developing a high through-put serology test for SARS-CoV2 antigens, using glycosylated modified immunogenic SARS-CoV-2 antigens, profiling patients' antibody repertoire",2020,-99,University of Edinburgh,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C04675,C19-IUC-164,ACTT-DMID20-0006/INSIGHT-010,"The Adaptive COVID-19 Treatment Trial (ACTT) aims to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. One of the earliest treatments arms - antiviral drug remdesivir - was fast tracked into the clinic after Stage 1 results reported in May 2020. Results from Stage 2 were published in December 2020 and combination of remdesivir and baricitinib given emergency use authorisation by the FDA. While new treatments are being tested in Stage 2, the ACTT trial itself will instead continue under a new master protocol; ACTIV-3 (INSIGHT-14).",2020,-99,MRC Clinical Trials Unit at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C04676,C19-IUC-165,ICOS (INSIGHT-11),"ICOS (An International Observational Study of Outpatients with SARS-CoV-2 Infection) aims to assess the influence of demographics, source(s) of infection, co-morbid conditions, immunosuppression, and other clinical risk factors, for the global cohort and by geographic region. It opened to enrollment in June 2020.",2020,-99,MRC Clinical Trials Unit at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C04677,C19-IUC-167,CoroNerve studies,This observational study seeks to identify neurological and psychiatric complications of COVID-19 in hospitalised patients; enrolling since April 2020.,2020,-99,MRC Clinical Trials Unit at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences, +C04678,C19-IUC-173,COVAC-1 and COVAC-2 RNA vaccine,To evaluate safety and efficacy of a candidate RNA vaccine against the spike1 glycoprotein that binds to the ACE2 receptor and facilitates entry compared to placebo. Phase 1 has started enrollment of healthy volunteers. http://www.isrctn.com/ISRCTN17072692,2020,-99,MRC Clinical Trials Unit at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Phase 1 clinical trial, +C04679,C19-IUC-226,Updates of health records for COVID-19 research,"Crucial new data on the health of 500,000 UK Biobank participants are being made available to scientists tackling the COVID-19 emergency. The pioneering UK Biobank resource, which follows the health of 500,000 volunteers in England, Scotland and Wales, is well placed to help answer a wide range of questions about the pandemic. Results of COVID-19 tests for UK Biobank participants (both positive and negative test results) are now availale for research, together with regular updates of GP, hospita admission and death data.",2020,-99,UK Biobank,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Epidemiological studies,, +C04680,C19-IUC-227,UK Biobank SARS-CoV-2 Serology Study,"Thousands of UK Biobank participants are being asked to take part in a major government study to measure the extent of coronavirus infection in different regions across the UK. Those who agree to take part will provide monthly blood samples for at least six months so that their levels of immunity (antibodies in their blood) can be measured. Researchers will use the information to determine the extent of the infection in different regions across the UK and to understand how long antibody levels persist following infection. This major study will complement existing studies, such as the ONS Covid-19 Infection Survey, which through nasal swabs is testing for presence of the virus and will collect blood samples from 1,000 adults in English households. By collecting blood samples from 20,000 participants across the UK to understand immunity to Covid-19, UK Biobank will contribute to national efforts to ease lock-down measures.",2020,-99,UK Biobank,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics, +C04681,C19-IUC-242,An equity focused rapid review of the epidemiology of COVID-19,To rapidly assess the available epidemiological evidence on social factors that predict developing SARS-CoV2 and the prognosis of COVID-19 disease in those affected. This will provide information to assist with healthcare planning for COVID-19 diagnosis and treatment,2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics, +C04682,C19-IUC-245,Impact of school closures on socioeconomic inequalities in children's wellbeing and development,"To identify potential impacts of school closures on socioeconomic inequalities in cognitive, social and emotional development, through a scoping review of the international literature on effects of school closures and secondary analysis of survey data. This will provide information to inform strategies for managing future school closures.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04683,C19-IUC-250,"Adiponectin as a link between Obesity, Male Sex and BAME ethnicity and COVID mortality","Male, BAME and obese populations have lower adiponectin levels than other populations. This study will use biomarker, genomic and cellular studies to examine the association of adiponectin levels with COVID pathological progression due to the specific effects of this complex protein on suppressing inflammation in the lungs.",2020,-99,MRC Metabolic Diseases Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Minority communities unspecified | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C04684,C19-IUC-251,Biomarkers of COVID pathology/progression,Using highly specialised peptidomics technologies we will undertake exploratory research to seek for biomarkers of COVID progression.,2020,-99,MRC Metabolic Diseases Unit,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C04685,C19-IUC-252,THEME 1 - Diagnostic methods evaluation and development,"Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes. Theme 1 is ""Diagnosis - methods evaluation and development"", how can we compare and evaluate testing methods, and improve coronavirus testing? Alongside re-purposing of facilities to conduct ~2,000 tests for SARS-CoV-2 virus for the NHS, the Crick will use this diagnostic capacity to perform longitudinal research studies to define critical clinical demographics.",2020,-99,Francis Crick Institute,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis, +C04686,C19-IUC-264,"How has COVID-19, and the restrictions on movement in the UK, affected use of green space?","This project aims to explore if, and how, the UK population changed their green space use following restrictions on movement on 23rd March 2020 due to the COVID-19 pandemic.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C04687,C19-IUC-265,Phosp-COVID,"This is a national project to collect samples and data from 10000 covid survivors at 3, 6 and 12 months post discharge from hospital, to understand long term outcomes. Led by researchers at Leicester and Birmingham, CMAR are leading the theme on sarcopenia. Funded to £8.5m and runs for 18 months.",2020,-99,MRC Versus Arthritis Centre for Muskuloskeletal Ageing Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Post acute and long term health consequences, +C04688,C19-IUC-266,Iron biology and COVID-19,"A feature of patients with severe COVID-19 infection is anaemia and changed concentrations of iron in the bloodstream. We are investigating whether the altered iron levels and the anaemia might cause less efficient immune responses against the virus, allowing the infection to persist. If so, therapies aimed at correcting iron imbalances might improve the outcome of infection.",2020,-99,MRC Human Immunology Unit at the University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C04689,C19-IUC-267,Complement levels in Black African men as a risk factor for poor COVID19 outcomes,Study of ethnic differences in complement pathway which may influence susceptibility to severe COVID in Black British people. Now involving collaboration with Kings College London and Cardiff University.,2020,-99,MRC Metabolic Diseases Unit,,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C04690,C19-IUC-268,Biomarkers of ACE2 inhibition,"SARS COV2 binds ACE2 to access cells, ACE2 is a key enzyme in teh breakldown of angiotensin a major stimulus to the hormone aldosterone which controls salt and potoassium homeostasis in the body. We are investigating whether this system is disturbed in COVID19 and whether this contributes to any of the cardiovascular complications of the disease",2020,-99,MRC Metabolic Diseases Unit,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C04691,C19-IUC-269,"Clinical trial of spronolactone + dexamethaosone, Part of ACCORD2",,2020,-99,MRC Metabolic Diseases Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C04692,C19-IUC-270,CVR CRUSH,"The CVR has established ""CRUSH"" (COVID-19 Drug-Screening and Resistance Hub) for the benefit of the UK academic and industrial community. CRUSH is a facility fully dedicated to screen anti-SARS-CoV2 drugs/ monoclonal antibodies and characterise the potential drug-resistant mutations induced by possible lead compounds. CRUSH will also monitor the presence of SARS-CoV-2 globally circulating strains with potential drug-resistant mutations and curate an open access database with this information.",2020,-99,MRC-University of Glasgow Centre for Virus Research,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation | Pathogen: natural history, transmission and diagnostics","Pre-clinical studies | Pathogen genomics, mutations and adaptations", +C04694,C19-IUC-272,How does SARS-CoV-2 affect the nervous system?,"In this biobanking study, blood and CSF has been collected from COVID-19 patients with neurological symptoms. The study will investigate CNS inflammation, injury and vascular dysfunction using state-of-the-art CSF and blood biomarkers.",2020,-99,UK Dementia Research Institute,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C04695,C19-IUC-273,Epidemiology - The REACT Programme,"The REACT programme, the largest of its kind, is a series of studies that are monitoring how the COVID-19 virus is spreading across England. Commissioned by the Department of Health and Social Care, the REACT series of studies are being carried out in partnership with Imperial College Healthcare NHS Trust and Ipsos MORI. The research is offering insight into infection rates broken down by geography, age, sex, ethnicity, key worker status and symptoms. REACT is the largest study of its kind and offers a comprehensive approach to antigen and antibody testing including a large sample (5000+) of keyworkers. REACT 1 and REACT 2 participants are to be followed up via NHS records. Patients who tested positive for COVID-19 (either antigen or antibody) will be followed up for neurological diseases via NHS records.",2020,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C04696,C19-IUC-277,Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts,"Researchers from the University of Bristol used data from the Avon Longitudinal Study of Parents and Children and Generation Scotland to Evidence to find out how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and whether there are groups at greater risk of poorer mental health during the pandemic? there was evidence that anxiety and lower wellbeing but not depression, had increased in COVID-19. The percentage of individuals with probable anxiety disorder was almost double during COVID-19. Depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity.",2020,-99,University of Bristol,,Human Populations,Unspecified,Unspecified,Unspecified,Women | Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04697,C19-IUC-278,COVID-19 Mapping and Mitigation in Schools (CoMMinS),"CoMMinS aims to give us an understanding of COVID-19 infection dynamics centred around school pupils and staff, and onward transmission to family contacts. The project will run during the 2020/21 school year as the reopening of schools in September will bring new challenges and new opportunities to study the natural history of COVID-19 in young people. The project will collect data from 4000 school pupils and 1000 staff in Bristol schools, including a monthly COVID-19 test. There are several nested projects including a study of the impact on mental wellbeing and evaluation of a handwashing intervention.",2020,-99,University of Bristol,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C04698,C19-IUC-279,Testing an alternative enzyme for COVID-19 antibody testing,"Testing an alternative enzyme to enhance COVID-19 antibody testing. This pilot project will serve as a proof of concept, providing a potentially valuable resource and alternative in COVID-19 antibody screenings.",2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C04700,C19-IUC-281,Harnessing the inherent immunosuppressive properties of allogenic mesenchymal stem cells (MSCs),Aiming to harness the inherent immunosuppressive properties of allogenic mesenchymal stem cells (MSCs) which can be used to treat severe inflammation in the lungs. The team are seeking to identify therapies using small-molecules that could address patients experiencing severe Covid-19 inflammation in their lungs without the need for cell transplantation.,2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C04703,C19-IUC-284,National Study of Health and Relationships during Covid-19 (Natsal-Covid Study),"This national online survey of 6,000 participants aged 18 to 59 seeks to understand changes in sexual behaviour in Britain during the Covid-19 pandemic and assess the impact on sexual and reproductive health. The project includes follow-up interviews with around 40 survey participants to explore sexual partnerships across households, unmet health needs and relationship difficulties. The project is co-led by Kirstin Mitchell and comprises the researchers from University of Glasgow, UCL and LSHTM responsible for the National Surveys of Sexual Attitudes and Lifestyles (Natsal). The findings will seek to capture the excess sexual and reproductive health morbidity arising from the Covid-19 and social restrictions, and will contribute to SRH service and policy planning, modelling of STI transmission, and understanding of anomalies in routine SRH data over the course of the pandemic.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04706,C19-IUC-292,Identification of COVID-19 genetic risk factors,"Application of novel phenotype prediction algorithm to DNA data from direct-to-consumer tests collected via online participation and to participants from the UK, Italian and Spanish Biobanks who have tested positive for coronavirus, with aim to identify genetic risk factors",2020,-99,MRC Laboratory of Molecular Biology,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom | Italy | Spain,Epidemiological studies,Disease susceptibility, +C04707,C19-IUC-293,SARS-CoV-2 entry intro the cytosol,This study aims to better understand the factors that control the mechanism of viral entry in order to target more effective compounds that could inhibit viral infection in patients. The study will also investigate whether viral entry can be prevented by manipulating endolysosomal permeability.,2020,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04708,C19-IUC-294,The Impact of maternal immune activation on infant brain,"A longitudinal follow-up study of foetuses and infants exposed to COVID-19 and other sources of maternal immune activations, to assess the impact on the developing brain.",2020,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Human Populations | Other,Unspecified,Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Immunity | Disease pathogenesis | Indirect health impacts, +C04709,C19-IUC-295,Functional screenings for inhibitors of SARS-CoV-2 Spike protein-induced cellular syncytia identifies approved drugs for COVID-19 therapy,"Post-mortem analysis of lungs from COVID-19 patients revealed the presence of numerous pneumocyte syncytia (cells that have fused with each other to form large multi-nuclear structures). Since the expression of the SARS-CoV-2 Spike protein in heterologous cells results in the formation of syncytia, this system was used to screen for FDA/EMA-approved drugs that inhibit Spike-mediated heterologous cell-cell fusion. Of the successful drugs isolated in the screen, three of them were studied further. All three, in addition to inhibiting syncytia formation, also inhibited viral replication. The top candidate was found to also be an inhibitor of a calcium-activated chloride channel that is involved in cell-cell fusion. In our lab at the Centre for Developmental Neurobiology, KCL, we used electrophysiology to show that cells expressing the SARS-CoV-2 Spike protein have an increased channel activity in line with the idea that the virus stimulates syncytia formation via its activation. Our data may also help explain some of the side-effects of COVID-19, which include alveolar oedema and diarrhoea, both of which could be potentially linked to the activity of this channel.",2020,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04710,C19-IUC-302,ES/V009427/1 - New project grant,"Researchers at the centre are co-investigators on a new UKRI covid award; Psychosocial effects of the COVID-19 pandemic. The project aims to understand and mitigate the psychological and social impacts of COVID-19 and the lockdown on primary school children. The project will focus on the most vulnerable children identified as 'at risk' for mental health problems, by re-assessing a cohort now aged 5 to 10 years, to evaluate social and emotional impacts and how negative consequenses can be mitigated.",2020,-99,MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04711,C19-IUC-305,"Mechanism of the macrophage response to COVID-19 in humans, with the intent of understanding the cytokine storm","A major cause of death from COVID 19 is due to a 'cytokine storm'; an overreaction of the body's immune system including white blood cells called macrophages. This project seeks to understand whether COVID19 directly interacts with human macrophages to induce a strong inflammatory response and if so, what are the mechanisms behind this response. The aim is to then define intervention strategies targeted at macrophages to mitigate the response in humans.",2020,-99,MRC Centre for Reproductive Health at the University of Edinburgh,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis", +C04712,C19-IUC-306,Home BP monitoring,"Rapid changes from face-to-face consultations to home monitoring has affected many aspects of NHS services. Here, the researchers will examine home-monitoring of blood pressure (BP) to high-risk and shielded pregnant women across Scotland during the pandemic. The aim of this study is to investigate the impact and acceptability of rapid rollout using a mixed methods approach looking a data driven service evaluation and a series of qualitative interviews with service users and providers.",2020,-99,MRC Centre for Reproductive Health at the University of Edinburgh,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04713,C19-IUC-309,Impact of the pandemic on maternity services,"Researchers have lead an assessment of NHS maternity and gynaecology units across the UK by surveying junior doctors working in Obstetrics and Gynaecology, and looking at service provision for women's health care during the pandemic. The results have been published in BJOG.",2020,-99,MRC Centre for Reproductive Health at the University of Edinburgh,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health service delivery, +C04714,C19-IUC-314,Covid-19 tracking survey (elderly and healthcare workers) - LINKAGE-Camden,"This involves two population COVID-19 tracking projects in a Camden based cohort with blood sample capture. In older people, the aim is to assess the incidence, risk factors, and determinants of outcomes using gene expression, serology and co-infection data along with hospital data of those admitted. In birth cohorts, short to long term impacts on health will be assessed as well as life course determinants of resilience to major shocks.",2020,-99,MRC Unit for Lifelong Health and Ageing at UCL,,Human Populations,Unspecified,Newborns (birth to 1 month) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts, +C04715,C19-IUC-316,Southall And Brent REvisited Study (SABRE) COVID-19 sub-study.,"The aim of this study is to collect insights into how the COVID-19 pandemic has affected different aspect of the lives of SABRE, a longstanding tri-ethnic population-based UK cohort. The survey covers topics including physical health, health behaviours and mental health and social connectedness.",2020,-99,MRC Unit for Lifelong Health and Ageing at UCL,,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C04716,C19-IUC-317,DECOVID (MRC Biostatistics Unit),We are one of the DECOVID analytics teams that aim to answer clinical questions related to COVID-19 using data from digitally-matured NHS Trusts.,2020,-99,MRC Biostatistics Unit,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,, +C04717,C19-IUC-319,"Associations between 25OOH)D status, BMI, ethnicity between SARCS-COV-2 positive cases and controls.","A collaboration with University of Surrey using UK Biobank data to describe associations between 25(OH)D (biomarker of vitamin D) status, BMI, ethnicity between SARCS-COV-2 positive cases and controls.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C04718,C19-IUC-320,Vitamin D and SARS-CoV-2 virus/COVID-19 disease,"A narrative paper and review of current guidance, collaboratively written by UK and Ireland Vitamin D experts regarding vitamin D and prevention of infectious diseases, including COVID-19.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C04719,C19-IUC-321,COVID-19 extension to the Hertfordshire Cohort Study,"The Hertfordshire Cohort Study COVID-19 extension is a telephone-based questionnaire, administered to Hertfordshire Cohort Study participants who have recently being taking part in a behavioural study of nutrition and physical activity. The questionnaire focusses on the impact on daily living, social isolation and lifestyle during the 2020 Lockdown. The work will help us understand how older people living in the community were impacts by the lockdown and how support could be improved in the future. We would also like to understand how Public Health messages can be improved for older people during future pandemics.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Social impacts, +C04720,C19-IUC-322,The role of angiotensin related medications in COVID-19 risk,A collaboration with UK Biobank and QMUL to investigate role of angiotensin related medications in COVID-19 risk.,2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C04721,C19-IUC-323,Ethnicity and sex specific differences in COVID-19 susceptability,A collaboration with UK Biobank and QMUL to investigate possible explanations for ethnicity and sex specific differences in COVID-19 susceptability.,2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C04722,C19-IUC-324,Investigation of role of frailty in COVID-19 susceptability,A collaboration with UK Biobank investigating the role of frailty in COVID-19 susceptability.,2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C04723,C19-IUC-325,Exploring how young people have been coping under the COVID-19 pandemic,"This research project aimed to explore how young people have been coping under the COVID-19 pandemic, how the experience has influenced young peoples' mental and physical health and future views.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04724,C19-IUC-326,Southampton COVID-19 Testing Programme Pilot Study,"The Southampton COVID-19 Testing Programme Pilot Study is assessing the feasibility of at-home COVID-19 saliva testing for whole households to help stop the spread of the virus as lockdown restrictions are eased. Providing saliva for testing is much simpler than the swab tests currently in use. The samples are tested using a technique called direct reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is simpler, faster and cheaper than the usual method of RT-qPCR. What we learn from this first phase will help us assess the feasibility of more widespread testing in the future. Testing started on June 22nd and finished on July 25th 2020.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C04725,C19-IUC-328,"Wash, Walk, Wear - behavioural change to reduce hospital cross-infections","This campaign headed by University Hospital Southampton NHS Foundation Trust aims to reduce hospital Covid-19 cross-infection rate to zero, using the messages and logos for WASH, WALK, WEAR. The Trust understands that to achieve this ambition, significant behavioural change in staff is going to be needed to maintain physical distancing, wearing of masks and frequent hand washing. This comes at a time where a lot has been asked of staff, and many are tired and don't want to be told what to do. The Trust is open to innovative ways to help people remember what to do, rather than repeatedly telling them. To achieve this, behavioural insights are required to inform the city-wide campaign, to take it from awareness-raising to action. Guidance is thus being provided as to how to make the required behaviours more likely, as well as ideas for evaluation/measures of success so that this campaign can be shared with other Trusts/communities as an example of good practice.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings, +C04726,C19-IUC-329,Healthy Conversation Skills to support isolated people,"Face-to-face Healthy Conversation Skills (f2f HCS) are the mode of delivery of Making Every Contact Count in Wessex and other regions in England. During the Covid-19 pandemic, work with Health Education England colleagues to adapt our f2f HCS training has been undertaken to develop & deliver a 90min online ""Supportive Conversations"" training session for those supporting vulnerable, isolated people during the pandemic; around 60 people have been trained to date, largely working in voluntary and community organisations.  The aim is to provide them with skills to have more effective and supportive conversations to help people maintain good health and well-being. We are collecting pre-/post-training evaluation data which we will report on and submit for publication.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research on Capacity Strengthening,Individual level capacity strengthening, +C04727,C19-IUC-330,Exploring acceptance of a possible CHIM (Controlled Human Infection Model) for vaccine development,Working with BRC colleagues on a local public consultation to explore acceptance of a possible CHIM (Controlled Human Infection Model) as part of the effort to fast-track to a vaccine for Covid-19. Seven online focus groups were held with 57 young people aged between 20-40 years. The resultant paper was published in BMC Medicine thus informing others who might be interested in running a CHIM as to the views of the population likely to be recruited to such a trial.,2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies, +C04728,C19-IUC-331,The impact of COVID-19 pandemic on shopping and eating behaviours via the WRAPPED study.,"The impact of COVID-19 pandemic on shopping and eating behaviours is significant and has affected most of the population. We are undertaking a qualitative study with women from disadvantaged backgrounds to examine shopping patterns before the pandemic and changes to shopping, eating, and cooking patterns during the pandemic. Women participants aged 18-45 years from the WRAPPED study, a supermarket intervention study assessing the impact of product placement on the diets and purchasing patterns, were invited to take part in the semi structured interviews. These interviews aimed to collect data on shopping patterns before and during the pandemic, stockpiling, grocery shopping experiences, adjustment to closure of places, cooking more meals at home and eating behaviours. Demographic data are available for the women and will enable greater understanding of influences of educational attainment on shopping and eating patterns during the pandemic.",2020,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C04729,C19-IUC-332,"COVIDITY-COHORT: using UK cohort studies to understand which genetic, demographic and lifestyle factors relate to cardiovascular health","In a collaboraton between researchers at University College London and University of Bristol, we will look into the susceptability to COVID-19 infection and advers outcomes from infection in the UK population. The researchers will use data from longitudinal population cohorts linked to national data resources such as primary care diagnosis, hospitalization and mortality due to COVID-19.",2020,-99,University of Bristol,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C04730,EP/N027167/1,Grand Challenge Network+ in Proton Therapy,"The aim is to estimate the impact of COVID-19 on proton therapy and radiotherapy (RT) services more generally at national and regional level across the UK. We will use our mathematical model of radiotherapy demand (MALTHUS) which was commissioned for the NHS by Prof Sir Mike Richards when he was Cancer Czar. Through adapting MALTHUS we will be able to understand the impact of COVID-19 on radiotherapy practice across the UK and to use it as a scenario modelling tool to provide a long-term assessment of how the provision of radiotherapy will change for different cancer anatomical sites as a result of COVID-19. MALTHUS uses factors relating to patient case-mix, indications for radiotherapy treatment and evidence-based radiotherapy fractionation which are encoded into decision trees representing cancers treated by radiotherapy. Base data for local-level population and cancer registrations were obtained from the National Cancer Intelligence Network and Office of National Statistics. Malthus uses a sophisticated discrete-event simulation algorithm that can provide statistically robust estimates of treatment demand. MALTHUS will be adapted to include new RT evidence and protocols, which reflect the current COVID-19 changes occurring within the NHS. This will allow for scenario-based service simulations that evaluates the practice changes, current reduction in cancer patients and potential backlogs of patients requiring RT and what it will mean for services and patients. Economic factors will be included through integrating NHS tariff charges. Initial service data will be obtained through the Christie NHS Foundation Trust's Big Data Radiotherapy project. MALTHUS is an active framework model used nationally and internationally. MALTHUS is already collaborating with Greater Manchester Cancer (part of the devolved health system) and the CRUK Radiotherapy Policy team. We will work closely with the Christie to develop the service scenarios and collaborate with their radiotherapy and lung cancer research projects, who are gathering COVID-19 RT activity and patient outcome data. This will enable the investigation of wider health economic impacts of changes made to current practice through using QALYs and cost-effectiveness analysis. The project will collaborate with two additional cancer centres to trial scenario simulations. If successful, we will work with national bodies (such as CTRad and RCR) to make the simulations available to all NHS radiotherapy services.",2020,-99,University of Manchester,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C04731,EP/R026939/1,The UK Catalysis Hub -'Core',"Cardiff University and Selden Research have a patented novel catalytic method of making long lived reactive oxygen species effective for pathogen kill and surface disinfection. https://patentimages.storage.googleapis.com/12/c4/b7/8f1ef5827dc436/GB2572364A.pdf The method involves passing a solution containing dilute hydrogen peroxide (H2O2) through a catalyst (a copper salt on alumina matrix) using a spray bottle with the catalyst in the nozzle. We have tested this with a range of microorganisms including Staphylococcus aureus and Candida albicans yeast and have achieved >5 log10 reduction in minutes. To date we have not examined virucidal activity but given the effect of our method on other microorganisms we anticipate it will be effective against enveloped viruses. Our work until now focussed on developing the method for use in the food preparation and agricultural industries and the key point is that no toxic residues remain on the surfaces that are treated, while also offering exceptional kill efficacy. The research programme will initially test the virucidal activity of our existing formulation on viruses including coronavirus standard test strain as a surrogate for SARS-CoV-2 (COVID- 19). We will then aim to modify and simplify the formulation to determine if we can replace hydrogen peroxide by air whilst maintaining the virucidal activity. We will also develop the use of aerosols so that the new method can be used to treat large spaces which could be applied in the disinfection of PPE for reuse or the environmentally non-toxic disinfection of transportation such as the internal spaces of ambulances, buses, trains and planes.",2020,-99,Cardiff University,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C04732,EP/R029563/1,"AutoTrust: Designing a Human-Centered Trusted, Secure, Intelligent and Usable Internet of Vehicles","TIME FOR INNOVATION IN COVID COSTS LIVES. Covid is causing all of us to accelerate our work, while limiting our ways to work. By restricting many of us to communicate by video conferencing, collaborative practices are actually slowed or otherwise compromised - by lack of familiar tools and interactions, and by negative side effects from the current tools themselves never designed for these purposes. Indeed, by now, all of us working with others in research, especially in virtual teams, have encountered ""zoom fatigue."" The effects on performance are almost as critical as sleep deprivation in limiting insight, making errors and, critically, losing time when there is urgency not only to invent new solutions but to make decisions that affect everything from PPE being, to creating a new algorithm to better crunch data to come up with new models for drug discovery. STRATEGIES FOR RAPID IMPACT ON ENHANCED INNOVATION. Our preliminary work shows that current, especially video dominant, sedentary approaches disrupt the already limited communication cues that we use to signal intent, inducing fatigue and limiting the smoothness needed to facilitate insight. Similarly, these tools do nothing to accelerate what is known as 'swift trust' - essential for new teams in particular to form effectively and work as efficiently as possible. We have developed several strategies to address these shortcomings and rapidly enhance creative collaboration within current bandwidth and devices.",2020,-99,University of Southampton,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C04733,EP/S004505/1,A novel coating technology based upon polyatomic ions from plasma,"This project tackles fomite transmission to provide enhanced protection (key workers) and prevent (public) transmission during the current CoVID-19 (SARS-CoV-2) outbreak, and to safeguard against future pandemics. As we understand more about how the virus is spread (by droplets) there is a need for practical interventions to prevent spread from surfaces. Six months allows PI (Short) to work with Virologist (Munir). First tangible results will be < 6 months. Coatings are assessed within Cat 3 facilities using plaque and molecular assays to determine deactivation of SARS-CoV-2 by contact. Candidate coatings will be assessed on 8 real-world materials and leveraging upon a significant knowledge of translation and scale-up, within < 12 months, real-world objects will be coated and deployed.",2020,-99,Lancaster University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings", +C04734,EP/S019901/1,Chemical biology tools for investigating the chemistry of cellular redox stress,"The primary cause of death resulting from infection with (SARS-CoV-2) is pneumonia, which causes acute respiratory distress syndrome (ARDS). Studies have shown that 14% of SARS-CoV-2-related cases of pneumonia are severe and ≈5% of infected patients require intensive care. The disease is fatal in around 60% of severe and critically ill patients, with evidence showing that hypoxemia (low SpO2) is linked to a fatal outcome. It is currently unclear what leads patients to develop these severe symptoms, which can often occur after the patients is seemingly recovering. Given the limited availability of intensive care beds and oxygen treatment, the identification of simple and reliable predictive biomarkers in hospitalised COVID-19 patients is essential to allow prioritisation of treatment. The tools that we will develop will allow accurate determination of SpO2 and CO2 levels simultaneously, allowing more informed and effective clinical decisions to be made. These tools will also allow the real-time monitoring of oxygen therapy, enabling clinicians to determine if this treatment is being used effectively.",2020,-99,University of Oxford,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management", +C04735,MC_PC_17210,Cohorts as Platforms for Mental Health research (CaP:MH)',"As stated by the World Health Organisation, understanding the effects of the pandemic on mental health is a global research priority. Using pre-pandemic baseline information and newly-collection information longitudinal studies can record changes to mental health over the course of the pandemic to contribute to the COVID-19 data-science programme coordinated by HDRUK. The Wellcome Trust COVID-19 secretariat for Longitudinal Population Studies (LPS) has developed a standardised questionnaire enabling ALSPAC and other LPS to measure COVID-19 symptoms/outcomes and associated outcomes linked to social distancing and the economic impacts of the pandemic. This has been adopted by >10 cohorts resulting in a multi-cohort resource with critical mass. With HDRUK we are linking these to NHS records in order to inform priority COVID-19 research. In immediate response to COVID-19, we developed and deployed a questionnaire to the original parents enrolled 1990-92 (G0: mean age ~58 years) and their offspring (G1: mean age 28 years): it received ~5000 responses in 9 days, and >7500 to date. We now have an exceptional opportunity to expand with follow-up questionnaires capturing longitudinal information on COVID-19 status and to assess the societal impact of the pandemic with a repeat of mental health questions. We request approval to reallocate £60,000 within our MH Pathfinder award. £20,000 for a third sweep of our COVID-19 questionnaire towards the end of 2020: the first questionnaire sweep was supported by the Elizabeth Blackwell Institute/ALSPAC and we are seeking support for the second sweep through an application to UKRI (under review). £40,000 to support COVID-19 MH analysis as a new MH Pathfinder exemplar project using linked NHS records and spanning multiple cohorts, including our Pathfinder partners at Born in Bradford (administered using the structure developed to support existing Pathfinder exemplars). We are able to reallocate these funds as TPP (a GP Software System Supplier), with whom we are intending to partner in order to develop a GP data extraction mechanism, are now willing to undertake this work pro bono.",2020,2020,University of Bristol,77400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C04736,MR/P022626/1,VACCINE - Development of novel picornavirus virus-like particle vaccines,"Virus-like particles (VLPs) are are the holy grail of vaccinology, presenting antigenic features of a viral pathogen in a safe, highly-immunogenic form. The focus of MR/P022626/1 is the development of VLP vaccine candidates for enterovirus 71 (EV71) and Coxsackie virus A16 (CVA16).If repurposed to address COVID-19, the EV71 work Leeds will be continued by a PhD student (Mona Shegdar, MS) alongside work continuing at NIBSC. Amended objectives (in italics) are below: 1. Selection of EV71 and CAV16 viruses and native empty capsids with enhanced stability.Already achieved for EVA71 but will not be undertaken for CAV16. 2. Acquisition/production of antibody reagents to distinguish 'native' (H) and 'expanded' (H) particles; assay development.Ongoing and will be completed by MS and at NIBSC. 3. Development of expression constructs; VLP production and characterisation.Work will be completed by MS. 4. Immunogenicity of natural and recombinant VLPs vs wt virions and VLPs and inactivated vaccines.Work will be completed by NIBSC. 5. Initiate comparable studies with other enteroviruses. Work will be undertaken by MS if time permits. We have developed a VLP scaffold system that allows the presentation platform and the glycoprotein antigen to be made separately and then combined in vitro. This scaffold system therefore allows optimal production protocols to be used for the separate components and means that a number of different antigens can be used individually or in combination on the same scaffold. They are therefore ideal as a rapid and flexible intervention strategy. Furthermore, such multimeric display of antigens has been shown to offer superior antigen presentation. The use of multiple antigens also offers the possibility of vaccines with broad cross-protective potential. In addition, the ability to 'add on' additional new antigens via a common linkage system allows for a rapid response to outbreaks by novel emerging viruses. Here, we will use our novel scaffold system to capture the SARS-CoV-2 glycoprotein receptor binding domain (RBD) and evaluate the antigenicity, immunogenicity and stability of the VLP vaccine candidates. Our VLPs are based on the hepatitis B core protein that expresses an affimer - this binds SUMO with high affinity and hence can capture SUMO-tagged proteins (journal.pone.0120751)A number of vaccine candidates are in development, but many of these rely on clinically unproven technology. However, there are commercially-available VLP vaccines made in yeast (against hepatitis B virus and human papillomavirus). Furthermore, a scaffold system allows the flexibility to respond both to the current SARS-CoV-2 pandemic but also to future disease outbreaks.We have the expertise and collaborators in place. The applicants and the PDRA (Natalie Kingston) have expertise in VLP vaccines and in production of VLPs in yeast (10.1128/mSphere.00838-19). Our collaborators Dave Stuart, Liz Fry and Tom Bowden (Oxford) have produced the RBD in mammalian cells. Mark Page, Nicola Rose at NIBSC have a wealth of expertise in evaluation of vaccine material and in immunogenicity assays and we have the support of Incepta vaccines in Bangladesh.",2020,2021,University of Leeds,98219.31,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies,2017 +C04813,Unknown,A ZEBRAFISH MODEL TO STUDY SARS-COV-2 NEUROINVASION (NeuroCoVid project),"Invasion of the central nervous system, possibly via the olfactory nerve, is suspected to play a role in respiratory failure of Covid-19 patients. This project aims to test SARS-CoV- 2 neuroinvasiveness in vivo in a zebrafish model. The zebrafish larva allows easy visualization of the entire nervous system in vivo or with whole mount fixed samples. It could provide a cheap, genetically tractable model to analyze viruss dissemination in its host and effect of antiviral drugs.",2020,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Disease models, +C04814,Unknown,Air monitoring risk area [Co-funded by CEA],"Following the acceptance of the ANR flash project Covid-19 ""ARISE"", the CEA-Leti teams mobilized in record time, and are working to develop a prototype air analysis instrument for the monitoring of the pathogen SARS-CoV-2 in the form of droplets or aerosols. The ARISE project, carried out in partnership with the Pasteur Institute, proposes the development and validation of an analytical chain for air monitoring of areas at risk, in order to control confined environments. This solution will be based on an electrostatic air sampler to collect submicronic and micronic particles coupled with a microfluidic module containing freeze-dried biological reagents, designed for rapid in situ isothermal amplification of viral nucleic acids. This strategy will allow reliable detection of viruses in up to 30 minutes. The system will be compact and lightweight and will allow for semi-continuous on-site monitoring. Particular attention will be paid to its development to ensure its use by non-experts.",2020,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C04815,Unknown,COVID-19 - The Bioinformatics and Biostatistics Hub on the front line (GISAID Project),"Like many other research teams at the Institut Pasteur, the Bioinformatics and Biostatistics Hub is engaged in fighting against the COVID-19 pandemic by participating in the curation of GISAID data (Global Initiative on Sharing All Influenza Data). The Hub is the service division of the Computational Biology Department, and is composed of 50 experts in biostatistics and bioinformatics. At the end of March 2020, following a discussion on phylodynamic questions with the Evolutive Bioinformatics Unit at the Institut Pasteur, GISAID asked for help with processing the increasingly abundant data that was being submitted as well as with maintaining its quality. A solution for managing this essential resource was reached rapidly. The Hub agreed to accommodate this request, and as of April 1st, thirteen of its members have been actively curating, on a daily basis, data received by the consortium. The GISAID initiative, launched in 2006 following the 2006 bird flu epidemic, fosters international sharing of sequences associated with this virus as well as related geographical, clinical and epidemiological information. Its scope is now being extended to species associated with avian and other animal viruses, today including SARS-CoV-2, to help the scientific community understand how viruses evolve, spread and potentially trigger pandemics. (To boot, the National Reference Center for Respiratory Viruses (Including Influenza) at the Institut Pasteur shared the two complete sequences of viruses taken from two of the first French cases on this platform on the 30th of January, 2020.) The Initiative guarantees that access to data in GISAID is free for everyone, provided that individuals log in and agree to respect the GISAID sharing mechanism governed by its database access agreement. As of the 15th of April 2020, more than 130 SARS-CoV-2 genomes had been submitted by Institut Pasteur teams since the month of January. Concretely, Hub members are on duty every day, from midday to midnight, to process the numerous genomes of SARS-CoV-2 submitted (which range from a few dozen to several hundred per day) in order to validate the quality and reliability of sequences and their metadata. The objective is to standardize the metadata in order to facilitate searching the database, and to check the consistency of the assemblies. More than 9,000 genomes are accessible on the GISAID web site today (April 15, 2020), of which almost 3,000 have been curated since the 1st of April with the help of the Hub. This data is used, among other things, by nextstrain, an open source project aimed at providing a snapshot of the evolution of populations of pathogens via a modern and reactive interface. In addition to this action, the Hub remains available to campus scientists. More than ever the Hub is ready to provide its skills in experimental design, data processing, analysis and modelling, as well as in software, pipelines and web application development on priority projects related to COVID-19 research.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,Data Management and Data Sharing,,,,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Pathogen genomics, mutations and adaptations | Health information systems", +C04816,Unknown,COVID-19 RISK EVALUATION AMONG THE HOUSEHOLD CONTACTS OF THE FIRST CASES IN AFRICA (COVID-19 risk evaluation project),"Once the first Covid-19 cases will be identified, the spread of the SARS-CoV-2 will be related with the level of the transmission risk. This study aims to obtain an early understanding of key epidemiological characteristics in the family contacts in different African countries of the IPIN to inform decision makers about the potential spread and impact of SARS-CoV-2 infection in the closest contacts. The study will be carried out in household with at least 5 persons and during three weeks once the family index cases detected.",2020,-99,N/A,,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,Epidemiological studies,Disease transmission dynamics, +C04817,Unknown,"DECIPHERING THE VIRUS INTERACTIONS WITH THE ENTRY RECEPTORS IN HUMAN CELLS, AND THEIR POTENTIAL INHIBITION (DSAC project)",Researchers will develop and employ a workflow that combines cryogenic light and electron microscopy imaging modalities with computational analysis and data mining to determine high-resolution in-situ structural images of the virus-spike interactions with cell receptors and with the antibodies that abrogate their cell entry. These studies will provide a blueprint for the design of vaccines and therapeutics.,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04818,Unknown,DEVELOPING A RAPID DIAGNOSTIC TEST TO DETECT SARS-COV2 VIRUS IN VARIOUS ENVIRONMENT (POC Project),"The epidemy of the SARS-CoV-2 virus and its global spread urgently requires efficient means for rapid diagnosis, as well as detection in various environments (aside from clinical laboratories), such as airplanes, schools, potential animal carriers, etc. We have previously devised a colorimetric method to detect specific pathogen sequences using Rolling Circle Amplification (RCA) which could potentially be used for ""on site"" virus detection.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C04819,Unknown,DEVELOPMENT OF NOVEL NANO-BASED MULTI-EPITOPE VACCINE AGAINST CORONAVIRUS SARS-COV-2 - GENERATION OF HUMANIZED NSG TRANSFER MOUSE MODEL FOR VACCINE TESTING (VacciNanoCor project),"We hypothesize that it may be possible to generate protective anti-SARS-CoV-2 immuneresponse in humanized NSG transfer mouse model. This will be achieved by administering to them of lipid-based nanoparticles carrying peptide molecules, comprising dominant immunogenic B and T cell epitopes from coronavirus SARS-CoV-2. The epitopes will be predicted by EpiDOCK server for evaluation of peptide binding to HLA class II proteins.",2020,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Disease models, +C04820,Unknown,Drug Repurposing & Design to inhibit the SARS-CoV2 proteases (CoV2-Anti-protease project),Identification of antiviral molecules targeting SARS-CoV2 proteases. Structures of the proteases will be used to screen large chemical libraries in complement of the FDA approved drugs. High Througput Screening (HTS) using dual mCherry-Nanoluc reporter cell lines can screen thousands of compounds. Combined with virtual screening this allows coverage of a large chemical space including purchasable compounds libraries. The best hits will be further validated on SARS-CoV-2 growth assays. Validated hits will guide optimization of compounds.,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies, +C04821,Unknown,Evaluating the determinants of coronavirus tropism in 3D models of human pulmonary epithelia (TROPICORO project - TROPIsm of COROnaviruses),"This study will compare the tropism of SARS-CoV-2 and more benign human coronaviruses for primary epithelia of the respiratory tract, to determine whether tropism associates with pathogenicity. The research team will use models based on reconstructed human airway epithelia and take advantage of a lung-on-chip technology that mimics the pulmonary alveolae stretch associated with breathing to develop physiologically relevant models of SARS-CoV-2 infection.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04822,Unknown,EVALUATION OF CLINICAL PRESENTATION AND EVOLUTION OF SARS -COV-2 CORONAVIRUS INFECTION IN SENEGAL (projet SEN-CoV),"The overall objective of this study is to understand the main clinical, biological, virologic and immunological characteristics of Covid-19 cases detected in Senegal in order to inform the development and updating of health guidelines for cases management and reduce the potential impact of infection. A retrospective and prospective cohort study of Covid-19 confirmed cases will be performed.",2020,-99,N/A,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Africa,,,,,Senegal,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C04823,Unknown,INVESTIGATING THE ROLE OF APICO-BASAL PROTEINS DURING SARS-COV2 INFECTION (EPIC project),"Manipulation of the apico-basal Polarity pathways during infection is a strategy routinely used by numerous viruses. This leads to the mislocalization or degradation of the polarity proteins and participate to the disruption of the epithelial integrity. Nothing is known so far concerning SARS-CoV2 and polarity. In order to better understand SARS-CoV2 physiopathology, this study focuses on the expression pattern of apico-basal polarity proteins during SARS-CoV2 infection.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04824,Unknown,"LULISA PROJECT, BIOLUMINESCENCE AS A TOOL FOR HUMAN DIAGNOSTICS, FROM ALLERGY TO COVID19","The LuLISA (Luciferase-Linked ImmunoSorbent Assay) research project aims developing high throughput serological tests for epidemiological studies at local, regional or nation scales. In a recent scientific publication, concerning the detection and dosing of IgE specific to several allergens in patients' blood samples, the use of LuLISA proves to be a vastly improved detection method in comparison with the commercially available kits. The LuLISA has also been adapted to detect various human immunoglobulin types targeting SARS-CoV-2 coronavirus proteins, and it is currently being used as one of the reference methods to evaluate the progress of collective immunity in Covid-19 in France, in collaboration with Santé publique France and several hospitals. This project involves scientists from the Institut Pasteur (Dept. of Immunology and Structural Biology and Chemistry), the CNRS (UMR3523) and the Inserm (U1221, U1222 and UMR1043) in the design of an original assay1 related to an ELISA (Enzyme-Linked ImmunoSorbent Assay). https://www.pasteur.fr/en/research-journal/news/lulisa-project-bioluminescence-tool-human-diagnostics-allergy-covid19",2020,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity, +C04825,Unknown,MECHANISMS OF INTERCELLULAR SPREADING OF SARS-COV-2: ASSESSING THE ROLE OF TNTS TO ESCAPE IMMUNE SURVEILLANCE AND EXPAND TROPISM AND PATHOGENICITY (COVID-Spreads project),"We will study the mechanism of spreading of SARS-CoV-2 between permissive (eg; epithelial) and non-permissive (eg; neuronal) cells, and investigate the role of TNTs, as well as the dependence on the ACE2 receptor. Our cryoEM and FIBSEM set up, will provide unique structural information about this process. Overall, this project will allow understanding the mechanism of the viral neurotropism, as well explain its immune evasion capacity.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C04826,Unknown,MODELING HUMAN SARS-COV-2 INFECTION IN MICE WITH HUMAN LUNG XENOGRAFTS (Cov2-HuLung project),To date there is no specific therapeutic treatment or vaccine for COVID-19 caused by the SARS-CoV-2 virus and relevant animal models that mimic human COVID-19 pathologies are lacking. We will generate two novel humanized mouse models: HuLung mice (human lung) and HIS-HuLung mice (and human immune system and human lung). Infection of HuLung and HIS-HuLung mice with SARS-CoV-2 will provide an in vivo model for viral replication and will enable the study of pathological mechanisms provoked by the anti-viral human immune responses to SARS-CoV-2.,2020,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models", +C04827,Unknown,NEUROLOGICAL IMPLICATIONS OF SARS-COV-2 INFECTION - A TRANSVERSAL STUDY (Neurological project),"The infection of the nasal mucosa and the lungs by CoV-2 may spread to the CNS, including the brainstem, thereby playing a potential key role in the severe respiratory distress observed in COVID-19. Although several clinical observations support this hypothesis, the knowledge in this field is very limited. To fill this gap, we will investigate CoV-2 neuroinvasion in humans, animal models, and cell culture-based experimental models and decipher the molecular mechanisms involved. Results of this project will provide clues on whether targeting potential neurotropism of CoV-2 may be relevant approach for experimental therapeutics in Covid-19.",2020,-99,N/A,,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,Clinical characterisation and management,Disease pathogenesis, +C04828,Unknown,NICOTINIC MODULATION OF SARS-COV-2 INFECTION IN THE BRAIN (NicoSars Project),This project aims at experimentally testing the hypothesis that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.,2020,-99,N/A,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,Clinical characterisation and management,Disease pathogenesis, +C04829,Unknown,RBCG VACCINE SECRETING SARS-COV-2 ANTIGENS (rBCG vaccine project),"Mycobacterium bovis BCG is a live attenuated vaccine that is used since almost 100 years for the vaccination against tuberculosis, with a solid safety record in billions of immunocompetent individuals. The aim of the project is to construct recombinant BCG strains that express viral protein(s) of the SARS-CoV-2 virus in fusion with the 6 kD early secreted antigenic target (ESAT-6), secreted by the type VII secretion systems.",2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Vaccines research, development and implementation",Pre-clinical studies, +C04830,Unknown,SEQUENCE THE COMPLETE GENOME OF COVID-19 DIRECTLY AND AT LOW COST FROM PREPARED RNA SAMPLES FROM PATIENTS (CAPTURE-COV project),to be able to sequence the complete genome of Covid-19 directly and at low cost from prepared RNA samples from patients. We plan to implement a capture sequencing protocol targeting the SARS-CoV-2 genome using three commercial sets of probes in parallel. Results will be compared with a bioinformatics analysis pipeline and shared via publication (Biorxiv preprint followed by classical peer review).,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C04831,Unknown,THE USE OF ARTIFICIAL INTELLIGENCE METHODS TO DISCRIMINATE COVID-19 FROM OTHER COMMUNITY ACQUIRED PNEUMOPATHY USING CHEST X-RAY AND CT IMAGES (AIMDP COVID-19 project),"Diagnostic of SARS-CoV-2 Coronavirus caused-disease (Covid-19) is a bottleneck in the immediate follow-up of patients. We propose automated detection methods based on Artificial Intelligence (AI) Algorithms (Machine Learning and Form Recognition), on chest Computed tomography (CT) or X-Ray images, to discriminate the Covid-19 disease from other Community Acquired Pneumonia (CAP). The methods will be used as complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests.",2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C04832,Unknown,URGENT DISCOVERY OF DRUG CANDIDATES THAT TARGET CORONAVIRUS SARS-COV-2 (DrugCandidates-SARS-CoV-2 project),rapidly provide drug candidates to treat victims of Covid-19. We will do this by applying our cutting-edge technologies and libraries to screen for viable active compounds that kill coronavirus. The strategy will employ phenotype screens (FPDD) that test for coronavirus inhibition using mouse (MHV-59) and human (OC43) virus as models for fast compound screening in cell culture. Direct-acting antivirals will also be sought via target-based screening (FBDD) as inhibitors of essential viral proteins of SARS-CoV-2.,2020,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,,Unspecified,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies, +C06030,60690,Reusable and high performance consumer face masks to protect against COVID-19,"Alongside other measures, public use of personal protective equipment (PPE) and particularly face masks can help to reduce transmission of the COVID19 virus. Public use of face masks is increasingly being recommended by public health bodies around the world. It is important that certified medical masks and respirators are prioritised for medical workers however. Current, non-medical face masks available for the public have limitations. Single use, surgical style masks, are not durable for reuse but using a new mask after each trip out would be expensive and create large amounts of waste. Cloth face masks that can be homemade or bought from textile and fashion companies are often better than no protection but these lack reliable testing and certification. They also must be used, removed and washed carefully. A consumer pollution mask can give better protection but is not specifically designed for infection control and may not be comfortable for long periods of use. We are testing a reusable face mask prototype which could effectively reduce transmission and can be quickly tested and manufactured. The mask is sustainably produced, durable, washable, and comfortable whilst offering good filtration performance. In this project we are working to produce and test improved prototypes and to scale production. In response to the COVID19 crisis, a huge new industry in consumer PPE is emerging. We are well positioned to help and to promote UK innovation in this field.",2020,2020,MODERN SYNTHESIS LIMITED,63941.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C06100,01KI20241A 01KI20241B 01KI20241C,"Dyspnoea and lung function with certified masks, home-made masks and optimized masks-a risk-benefit evaluation in patients with chronic lung diseases (BIO-PROTECT-Mask)","Because of the outbreak of COVID-19, many countries have recently regulated by law or strongly advice that face masks should be worn in distinct public environments in order to prevent further spreading of SARS-CoV-2. While there is a vivid discussion on the different types of certified or home-made masks and possible shortages in the supply chains, previous studies in other virus epidemics (influenza) indicate that compliance with wearing face masks and wearing time are the strongest predictors with respect a successful public healthcare intervention. One explanation for low wearing time might be the high pressure loss of most certified face masks that makes breathing difficult and wearing uncomfortable. Especially high-risk patients with chronic lung diseases may suffer from additional breathlessness while requiring a particularly high level of protection. Shortness of certified masks results in low-evidence recommendations for the use of home-made masks, however, it remains unclear whether the used materials provide reasonable protection against the transmission. In-depth studies that identify the best materials and layering are lacking, although experiments that would identify innovative materials with an optimal relationship of bioaerosol deposition and pressure loss might be a solution to improve the real-world effectiveness of mask wearing in public. In BIO-PROTECT we investigate filtration efficacy, pressure characteristics and effects on the load of breathing for different kinds of face masks in high- and low-risk populations and in relation to wearing time.",2020,2021,"Hochschule Heilbronn, Thoraxklinik Heidelberg gGmbH, Junker-Filter GmbH, Sinsheim",563341.8,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C06101,01KI20505,Effects of implementing advance planning for emergencies in inpatient facilities for elderly care under acute need for action due to the COVID-19 pandemic (BVP acute),"When making decisions about medical care, the patient's will plays an important role. The ""Treatment in advance planning (BVP)"" procedure enables the patient's willingness to be determined in order to plan treatments in a structured manner with trained staff. The BEVOR study examines whether this procedure can better take into account the patient's will in geriatric care facilities. Emergency situations occur more frequently in the COVID-19 pandemic, so crisis strategies are of great importance. The aim of BVP-Akut is, in view of the COVID-19 pandemic, to investigate to what extent in-patient care for the elderly takes the patient's wishes into account in emergency situations. The instruments that doctors should use to prepare advance health planning in dialogue with patients are examined. For this purpose, employees and residents of geriatric care facilities are asked: How do they view this type of determination of the patient's will? Is the tool used in your facility? Did this take treatment decisions in an acute emergency, including Covid-19, into account? The results of the BVP acute study should in turn flow into the BEVOR study and provide recommendations for action on the COVID-related crisis situation.",2020,2021,Ludwig-Maximilians-Universität München,67243.21,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Community engagement",2020 +C06102,01KI20521A01KI20521B01KI20521C,Allocating resources for cancer care in the context of Sars-CoV-2 outbreak (CancerCovid),"The outbreak of Sars-CoV-2 triggered unprecedented preparations for the care of patients with COVID-19 (1). In addition, access to hospitals and outpatient clinics was restricted due to specific hygiene regulations. Allocation of health resources in times of pandemic has potential clinical and ethically relevant implications for non-COVID-19 patients (2, 3). However, a systematic assessment of evidence and interdisciplinary analyses regarding ethical and social aspects related to care for non-COVID-19 patients during the pandemic is missing . The interdisciplinary CancerCOVID consortium will analyse possible implications of the outbreak of Sars-CoV-2 for the access, process and outcomes of care, with a focus on patients with cancer in Germany. For this purpose we will analyse quantitative data derived from the registry of colon cancer centres and data from the statutory health insurance on the care of patients with cancer, diabetes and coronary heart disease. In addition we will explore the ethical and psycho-social challenges perceived by patients and health professionals during the pandemic by means of semi-structured interviews. Based on the findings and together with major decision makers in the German healthcare system we will develop guidance for clinical and health policy decisions about priority settings regarding cancer care in times of pandemics and comparable major events.",2020,2021,"Martin-Luther-Universität Halle-Wittenberg, Technische Universität Dresden, Ruhr-Universität Bochum",543477.4,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in the Allocation of Resources | Approaches to public health interventions,2020 +C06103,01KI20179,Characterization of modulators of the angiotensin-renin system with regard to their effect on an infection with SARS-CoV-2 (CARS),"It is currently being discussed whether clinically used active ingredients such as modulators of the angiotensin-renin system could accelerate an infection with SARS-CoV-2. In order to clarify this question, a time-resolved virus infection assay will be established. The assay will help in identifying active substances that promote virus replication, in particular the effect of modulators of the angiotensin renin system on SARS-CoV-2 cell cytotoxicity. In addition, it was postulated that the ACE2 expression downregulated by SARS-CoV-2 is at least partially responsible for the permeability of the lung epithelium induced by SARS-CoV-2 and related lung injury. Therefore it should be tested whether modulators of the angiotensin-renin system affect the permeability of the epithelial tissue. Our findings can fundamentally contribute to the treatment of patients who use modulators of the angiotensin-renin-systems.",2020,2020,"Fraunhofer-Gesellschaft, München",58500.01,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06104,01KI20218,Use of human lung tissue explants to analyse immunomodulatory approaches for the treatment of COVID-19 caused by the novel SARS-CoV-2 (CoIMMUNE),"COVID-19 is caused by the novel SARS-CoV-2 that has infected more than two million humans and caused over 150.000 deaths worldwide. A vaccine and treatments are not available, which urges the development of new treatments, strategies to limit viral replication and to reduce new infections. SARS-CoV-2 induces a biphasic immune imbalance, characterized by the lack of a proper innate immune response in the early phase and the development of hypercytokinemia in the later phase. Here, we propose that application of human IFN-a subtypes or inhibitors of the immune regulatory kinase p38 provide realistic strategies to achieve either activation of the innate immune response in the early and the reduction of overshooting responses in the late phase, respectively. For rapid translation into clinical treatments, repurposing of pre-evaluated drugs and the use of pre-clinical study models should be conducted. This project employs human lung tissue to provide the first pre-clinical assessment of the antiviral and immunomodulatory properties of human IFN-a subtypes to identify the best candidate(s) to reduce viral replication and limit viral trasmission. In addition, we will deliver a pre-clinical testing of three pre-developed p38 inhibitors to provide experimental evidence that the overshooting cytokine response can be rebalanced by p38 inhibition and IC50 values in human lung tissue to allow rapid application in COVID-19 patients. This project has the potential to identify new efficient treatment options for COVID-19 suitable for translation into clinical applications.",2020,2021,Westfälische Wilhelms-Universität Münster,510578.44,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Immunity | Pathogen morphology, shedding & natural history",2020 +C06105,01KI20249,Clinical- and Omic- Based Analysis of Trajectory for COVID-19 Infection and Recovery (COMBATC19IR),"We aim to develop and validate Artificial Intelligence (AI) models that can reliably predict the course of COVID-19 progression and its complications via: 1) modeling patients clinical trajectories to understand their recovery and potential development of pulmonary complications, 2) characterizing diversity and virulence of the co-infecting viral and microbial community to understand disease mechanisms and severity, and 3) analyzing the host's biological makeup to understand the individual susceptibility to infections in low and high-risk individuals with pre-existing lung conditions. We validate and inform our AI models by clinical datasets and bio-samples collected from five different international patient cohorts: three cohorts in Munich and two in the USA. In addition, we track the COVID-19 patients for their post discharge health status focusing on lung related outcome measures at 3 months to confirm the recovery trajectory observed during hospitalization and compare their disease course and outcome to those recovering from similar-symptom diseases such as Influenza and community-acquired pneumonia. Based on the results obtained by our study, we develop a decision support system for physicians to allocate resources and to plan individualized follow-up care for at-risk patients.",2020,2021,Helmholtz Zentrum München,578425.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Americas | Europe,Innovation,,,Germany,Germany | United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C06106,01KI20117,An ethnographic study of the risks to and potentialities for social health during the Corona crisis (CoronaCare),"Political responses to the 'Corona pandemic' have predominantly focused on containing the spread of Sars-CoV-2 in order to maintain the physical health of the population. Everyone is simultaneously at risk of infection and a risk for infecting others. How humans as fundamentally social beings relate to each other is being radically altered in the responses to the 'Corona crisis'. CoronaCare examines how the political and societal responses to the pandemic influence social health, including how people negotiate the risks regarding their social health during the crisis. From the perspective of social medicine, we understand social health as the everyday social experiences at the level of communities, social networks, families and individuals. CoronaCare investigates four interconnected specific research aims: 1. To understand the tensions that arise in individuals' lives who live under political regulations working to minimize in-person (embodied) interactions; 2. to analyse strategies that individuals and communities develop to uphold social health; 3. to examine how caregivers in informal and institutional settings negotiate the tensions in their care relationships under current regulations of social isolation and 'risk worries' of the Corona crisis; and 4. to document how care receivers experience these tensions, in particular social isolation and the 'risky' relationship with their caregivers. CoronaCare deploys an ethnographic study design, utilizing qualitative telephone interviews, citizen science/ethnographic observational methods and surveys as data collection tools.",2020,2021,"Medizinische Hochschule Brandenburg, Neuruppin",497607.79,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2020 +C06107,01KI20377A 01KI20377B,COVID-19 Proteome Diagnostics: In-depth characterization of the plasma and urine proteome of COVID-19 patients for disease course prediction (COVID-19 ProDiag),"The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread around the world and infects millions of people. The high number of patients with severe COVID-19 response has led to unmanageable situations for healthcare systems, already resulting in thousands of deaths. To this end, we will use well-documented longitudinal COVID-19 cohorts, along with matching non-COVID-19 controls, comprising of plasma and urine samples collected in a highly standardized fashion. Each cohort will consist of a subgroup of patients showing mild symptoms and patients whose condition has deteriorated to a critical status. We will use a standardized sample collection pipeline including laboratory medicine analysis for consecutive sampling of a discovery and a validation cohort. Collection is ongoing with >400 samples per day (sample count: 7685 as of April 21, 2020). The samples will be selected based on clinical data out of our local COVID-19 patient registry CORKUM at LMU Hospital and analyzed using our cutting-edge mass spectrometry (MS)-based proteomics pipeline. The results will mirror the patients' disease state as reflected by concentrations of proteins in blood plasma and urine. We will apply our bioinformatics pipeline to uncover biomarkers and combine them in different risk assessment models (1) to differentiate between COVID-19 and non-COVID-19 patients, (2) to predict the disease trajectory in mild or severe disease courses, and (3) to predict the clinical outcome. This will ultimately allow personalized interventions and guiding the allocation of medical resources.",2020,2021,"Klinikum der Universität München (LMU), OmicEra",1264175.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C06108,01KI20390,"Covid-19 prevalence, disease course, and impact on pulmonary outcome in a TB cohort in four African countries (Covid-19_TB)","The aim of the project is to examine the effects of Covid 19 disease on tuberculosis patients in four African countries (Gambia, Mozambique, South Africa and Tanzania). For this purpose, appropriate clinical data are collected and analyzed on site. The frequency of the diseases and other epidemiological parameters of the SARS-CoV-2 infection as well as the clinical characteristics of the Covid-19 disease are to be described and compared with other patient groups and the healthy population. In addition, the interrelationship between pulmonary tuberculosis (and chronic lung disease after TB) and Covid-19 in terms of the severity and severity of both diseases is the subject of the project. The work is flanked by questions relating to social science aspects.",2020,2021,Ludwig-Maximilians-Universität München,57564,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Africa | Europe,,,,Germany,Mozambique | Gambia | South Africa | Tanzania | Germany,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06109,01KI20386,Randomized placebo controlled assessment of safety and efficacy of inhaled Aloxistatin (E64D) in 24 patients with CoViD-19. (CoViD-19-Aloxistatin),"The aim of this clinical study is to avoid severe courses of COVID-19 and thus reduce mortality from the disease. For this purpose, the safety and effectiveness of inhaled aloxistatin is checked in this project. For SARS-CoV-2 to be infectious, the virus must first be activated by various biochemical processes and penetrate the human host cells in sufficiently high concentrations. Aloxistatin is a protease inhibitor and - as already shown in mouse coronavirus model systems - prevents this activation of the virus at a crucial point. Building on the work already carried out, the preclinical testing of the inhalation of aloxistatin in an animal model and in a phase I clinical trial in humans will now be investigated. Inhaling the active ingredient should lead to higher doses of the active ingredient being achieved on site and the virus being inhibited shortly after infection. This should prevent severe disease progression from the start.",2020,2021,Universitätsklinikum Freiburg,2730249.11,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Veterinary",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies | Phase 1 clinical trial,2020 +C06110,01KI20143A01KI20143B01KI20143C,"Pharmacological induction of the Nrf2 pathway as immunomodulatory, cytoprotective, and antiviral intervention for COVID-19 (COVID-PROTECT)","A hallmark of infection with the highly pathogenic coronaviruses SARS-CoV, SARS-CoV-2, and MERS-CoV is that systemic inflammation and hyperinflammation-related airway damage (including acute respiratory distress syndrome, ARDS) are main determinants of severe morbidity and mortality. Modulating the host immune response might therefore constitute a highly effective addition to treatment regimens based on antiviral agents. The Nrf2 pathway constitutes a particularly attractive therapeutic target because (1) it has a variety of well-documented cytoprotective and anti-inflammatory properties and (2) its pharmacological induction protects mice from LPS-induced ARDS. Indeed, in our ongoing screen of anti-SARS-CoV-2 compounds we have found that the Nrf2 activator bardoxolone strongly reduces cytopathic effect and SARS-CoV-2 infectivity. We therefore hypothesize that Nrf2 inducers may prove useful to treat COVID-19. To test this hypothesis, we will assess anti-inflammatory, cytoprotective and anti-SARS-CoV-2 activity of bardoxolone and other Nrf2 activators using a pipeline based on human primary airway epithelial cells (both iPSC-derived and obtained from human lung) and immortalized cells and ex vivo cultured airway explants, also assessing protective effects in a model of airway epithelial barrier disruption as a proxy for ARDS. Considering that bardoxolone has already advanced in clinical trials to Phase III for other human disorders, further translation into clinical proof-of-concept studies for COVID-19 should be relatively straight forward and will be sought early on.",2020,2021,"Goethe-Universität Frankfurt, Medizinische Hochschule Hannover, Helmholtz-Zentrum für Infektionsforschung",636435.53,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06111,01KI20343,Understanding divergent host responses towards SARS-CoV-2 infection through precision immunology (COVIMMUNE),"SARS-CoV-2 infection can trigger a spectrum of host responses ranging from no symptoms to acute respiratory distress syndrome, multi-organ failure and death. Recovered individuals mount an effective immunity, however, some survivors develop COVID-19-associated morbidities, such as lung fibrosis or neurological symptoms. We postulate that the individual immune response during the course of SARS-CoV-2 infection may be an outcome-relevant factor. We have devised a precision immunology approach to systematically study immune functions in SARS-CoV-2-infected individuals that remain asymptomatic or develop COVID-19 with different levels of disease severity. Our central hypothesis is that innate and adaptive immune responses towards SARS-CoV-2 infection are influenced by genetic, epigenetic and environmental factors, which determine the host's ability to mount an efficient and appropriately controlled immune response and that may influence the development of COVID-19-associated pathologies. COVIMMUNE connects clinicians with core expertise in relevant clinical disciplines with experts in virology, immunology, bioinformatics and systems biology. Our approach aims to identify the factors that determine the immune response and clinical outcome of SARS-CoV-2 infection and will reveal predictive signatures to facilitate the development of superior biomarkers for disease susceptibility and personalized treatment.",2020,2021,Universität Bonn,2778578.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C06112,01KI20191,"Interrogating COVID-19, the lung microbiota, and therapeutic phages to mitigate secondary lung infection and inflammation (COVPHA)","The Coronavirus 2019-nCoV pandemic poses a heavy burden on both society and the healthcare system. Similar to other respiratory viruses, the rate of infection with acute bacterial pneumonia in COVID-19 patients is estimated to be up to 16%. To understand the mechanisms of secondary and co-infection in COVID-19 patients and to develop phage-based therapeutics against the associated bacterial pneumonia, we propose COVPHA, which benefits from our recent advances in high-throughput, culture-independent, but host-targeted methods. COVPHA aims to design a whole battery of phage-based therapies that apply multifaceted modes of action against bacterial secondary and coinfections associated with COVID-19 infection. Using an interdisciplinary approach, COVPHA will systematically identify the co-infecting bacteria in COVID19 patients by metagenomics (WP1), and isolate effective phages against target multi-resistant bacteria, using a revolutionary targeted culture-independent method, viral-tagging (WP2). We will determine the efficacy of different phage cocktails against target bacteria (WP 3), via our high-throughput in vitro system. Using tissue culture and in vivo animal models, we will comprehensively investigate the safety and efficacy of selected single phages and phage cocktails against target bacteria (WP4), to lay the foundation for compassionate use and an early clinical trial (WP5).",2020,2021,Helmholtz Zentrum München,1066667.1,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2020 +C06113,01KI20527,The Ethics of Livetracking in Connection with SARS-CoV-2 (ELISA),"Given the various measures that are being taken to contain SARS-CoV-2, the ELISA will investigate how livetracking applications are evaluated (descriptive level), and under what conditions they are morally justified (normative level). ""Anti-corona apps"", based on ""contact and proximity tracing"", focus on the location determination of users and monitoring of various vital indicators, which identify patterns that may be relevant in the case of coronavirus infection. While some consider individualized body-monitoring to be the ideal way to containing the pandemic, other groups recognize various risks. Against this background, the project will carry out an empirically informed and ethically sound balancing of interests. With a view to the goal of decelerating the spread of SARS-CoV-2 in order to relieve the healthcare system, it shall, as a first step, reconstruct a heterogeneous picture and, as part of a qualitative study, explore two fields of discourse: (a) ""medical/health professionals"" and (b) critical experts (IT-technicians, scienticts)"". Second, a normative assessment will clarify under which circumstances the collection of clinically relevant data is morally justifiable under the premise of informed user consent. Following empirical ethics methogology, interviews are conducted employing semi-structured interviews and combining these with normative analysis. The goal is to achieve a status quo for the perception of site-based monitoring of vital signs and, second, to develop recommendations for ethically justified applications and consent procedures.",2020,2021,Ruhr-Universität Bochum,155325.76,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures,2020 +C06114,01KI20201,CoV-2 specific serological diagnostics based on epitopes (EpiCoV2020),"The challenge for immune diagnostics dealing with Corona viruses like SARS-CoV-2 is the high background of infections with many different types from this subfamily of Orthocoronavirinae. This project aims at rapidly identifying individual peptide epitopes, both specific and unspecific, and mimotopes with improved affinities for serum antibodies from different patients. We are using resources readily set up for projects similar by the immunological and diagnostic challenge as well as readily available sera from a clinical partner. The project's goal is not only to identify a pool of such epitope/mimotope sequences with a proprietary statistical phage display method, NGS and a specially developed software, but also to rapidly validate them in arrays and in a second step in simple PoC devices to identify those suitable for diagnostic tools. They will differentiate between SARS-CoV-2 and other Corona virus infections, even if the antibody titers are decreasing after the infection. Peptide diagnostics can be reproducibly produced by any peptide manufacturer around the globe. This would contribute to worldwide standards in COVID-19 diagnosis and identification of persons with acquired immunity against the virus. In a more advanced setting differential epitope diagnostics will allow to correlate B-cell response with disease progression in a heterogenous background of recent Corona infections. Cytokine storm monitoring in some patients as well as vaccine development will require these tools. We expect first useful results already about 8 weeks after starting the project.",2020,2021,"Fraunhofer Gesellschaft e.V., Leipzig",675481.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06115,01KI20239A 01KI20239B 01KI20239C,Experimental and Computational analysis for linking infection dynamics and lung pathology in COVID-19 (ExComPat-COVID19),"The infection dynamics of SARS-CoV-2 within the lung and its association with disease progression is still incompletely understood. To which extent viral replication kinetics and virus-associated tissue pathology determine patient outcome remains an open question that is of urgent importance to advise effective treatment strategies. In this project, we will combine experimental data of lung organoids with detailed mathematical and computational models to assess SARS-CoV-2 infection kinetics under physiologically relevant conditions. By integrating spatially-resolved microscopy images with time course infection data of SARS-CoV-2 in lung organoids by mathematical analyses we will be able to quantify key parameters governing viral replication and spread, and their association with pathological changes. Extending the computational model to extrapolate infection dynamics within a human lung, we will be able to relate observed viral load kinetics in SARS-CoV-2 infected patients to expected tissue pathology and disease progression. This will help to assess the significance of viral load levels for associated lung pathology during infection. Our interdisciplinary approach will improve our understanding of SARS-CoV-2 replication and spread within lung tissue and its association with disease progression. Furthermore, the inferred computational model provides a tool to test the efficacy of antiviral therapies and represents a first step towards a mechanistic model of infection progression within tissue that could improve our understanding of individual patient outcome.",2020,2021,"Ruprecht-Karls Universität Heidelberg, Deutsches Krebsfoschungszentrum, Heidelberg, Ruprecht-Karls-Universität Heidelberg",284934.1,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06116,01KI20237,Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to prevent ARDS in COVID-19 pneumonia (GI-COVID),"In December 2019, an outbreak of viral pneumonia was observed in China which developed into a pandemic. A new type of corona virus (Sars-CoV-2) is considered to be the cause of this disease, which is known as COVID-19. In the course of COVID-19, pneumonia occurs in some cases, which can develop into an acute, life-threatening lung failure (respiratory distress syndrome, ARDS). This leads to destruction of the lung structure, which makes artificial respiration through a mask or intubation tube necessary. There is currently no specific therapy for COVID-19. The planned randomized, placebo-controlled clinical trial will investigate the efficacy of the drug substance Molgramostim (trade name Molgradex®) by inhalation in patients with COVID-19 pneumonia. Molgramostim promotes the formation and activation of immune cells and a similar preparation (sagramostim) is approved and used in the USA in a different dosage form in immunocompromised patients. Preclinical studies of Molgramostim and first applications of Sagramostim in patients with severe lung infections with organ failure have shown that inhaled administration significantly enhances the immune response of the lungs while accelerating the regeneration of lung tissue. The aim of this study is to measure whether the administration of Molgramostim (Molgradex®) compared to placebo leads to acute lung failure in fewer COVID-19 patients.",2020,2021,Justus-Liebig-Universität Gießen,2148006.78,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C06117,01KI20198A 01KI20198B,"Gastro-intestinal manifestations of SARS-CoV-2, importance for viral replication, spread and pathogenesis.(GI-SARS-2)","Although there are accumulating evidence that the intestinal epithelium is infected by SARS-CoV-2, the importance of this enteric phase for virus-induced pathologies, spreading and prognosis remain unknown. Here, we will engage in the comprehensive analysis of SARS-CoV-2 life-cycle in the human intestinal epithelium. (1) we will evaluate if there are infectious virus particles in stool. (2) we will develop standardized protocols to establish a robust measure for enteric virus shedding. (3) in organoids models, we will characterize how SARS-CoV-2 infects, replicates and is released from intestinal epithelial cells. This will provide the molecular basis of the enteric lifecycle and will enable us to determine the origin of the enteric phase (fecal/oral transmission vs. spreading from lung to gut). To these goals, we will exploit a pipeline combining single cell sequencing and spatial transcriptomics which we developed to study host-virus interaction. Combined with in-situ measurement of immune response in biopsies, we will define whether exacerbated gut inflammation contributes to the lung pathology observed in patients through cytokine storm-induced cytopathic effects. We anticipate that understanding the enteric phase of SARS-CoV-2 will provide us with critical pieces of evidence to outline novel perspectives to treat the disease and eradicate the virus. Most importantly, quantifying the relevance of fecal transmission and its link to SARS-CoV-2 etiology is urgently needed to implement epidemiological and societal measures aiming at monitoring and controlling the virus.",2020,2021,"Department für Infektiologie, Virologie Universitätsklinikum Heidelberg EMBL, The European Molecular Biology Laboratory",280237.45,Human Populations | Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06118,01KI2076,The RNA helicase eIF4A as a target structure for the development of new antiviral agents against,"The synthesis of viral proteins depends on the protein synthesis machinery of the infected host cell, as viruses do not have their own translation factors or ribosomes. Viruses often have functional RNA structural elements in their 5´-UTRs (untranslated regions) that are unwound by the RNA helicase eIF4A. Hence, eIF4A is a relevant broad spectrum antiviral target and inhibition of eIF4A, e.g. by rocaglate derivatives like Silvestrol, leads to broad spectrum antiviral effects. From our research we know that rocaglate derivatives can act like a clamp on viral RNAs at the surface of the RNA helicase eIF4A and thus prevent the synthesis of the virus proteins. All coronaviruses have pronounced and conserved RNA structures in their 5 'UTRs. So far we could show that MERS-CoV and HCoV-229E require eIF4A for their protein synthesis. SARS-CoV-2 has comparable RNA structural elements in its 5´-UTR. We therefore expect that the protein synthesis in SARS-CoV-2 is dependent on eIF4A. Effective eIF4A inhibitors could thus be a general treatment option for infections with coronaviruses. Since the mechanism of the Rocaglat effect on the eIF4A-RNA complex is well understood at the molecular level, this information can be used for the synthesis of new inhibitors. Rocaglate derivatives are very effective, but also have a complex structure. Hence the development of easily manufactured eIF4A inhibitors will be required. The goal of our HELIACOR project is to develop alternative eIF4A inhibitors that are easier to synthesize and can be used as a basis for lead optimization.",2020,2021,Philipps-Universität Marburg,70159.9,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06119,01KI20177,Immunogenetic Characterization of COVID-19 Disease (IC-COVID-19),"The SARS-CoV-2 pandemic will remain a world-wide threat for the next year. It is unknown why some people get severely ill while others have mild or even asymptomatic infections. With this epidemiological study we want to investigate immunogenetic parameters which may determine the clinical course of COVID-19. We plan for a cohort study with approximately 10,000 patients to test two hypotheses: 1) Patients who present at a testing site with SARS-CoV-2 show a specific repertoire of Human Leukocyte Antigen (HLA)- and Killer Immunoglobulin-like Receptor (KIR)-genes. 2) Patients with severe COVID-19 courses have a different immunogenetic HLA- and KIR-gene repertoire compared to patients with mild or moderate symptoms. The hypotheses will be tested in a case-control study and a cross sectional study. We will use leftover material of the diagnostic pharyngeal swab for HLA- and KIR-genotyping. In the cross-sectional study the genotype distribution will be compared among patients with different disease courses. For the case-control study we will use genotype information available on more than 7 million stem cell donors registed with DKMS. If high risk ratios can be revealed for certain genotypes, this information will help identifying high risk individuals among patients and health care workers by a simple non-invasive genetic test. High risk individuals may benefit from more stringent isolation or pre-emptive measures while low risk individuals, who more often have asymptomatic infections, should strictly wear protective masks in order not to spread the virus.",2020,2021,"Universitätsklinikum Carl Gustav Carus, TU Dresden",415317.94,Human Populations,Unspecified,Unspecified,Unspecified,Other,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C06120,01KI20206,Identifying Immune Targets to treat severe COVID-19 lung disease (IT-COVID-19),"While most patients recover from SARS-CoV-2 infection, some progress to acute respiratory distress syndrome requiring mechanical ventilation with a high mortality of 20-30%. This progression might be due to an overwhelming immune reaction. Thus, reducing the hyperinflammation seems to be an ideal therapeutic approach. However, considering the functional heterogeneity of the immune cells, it remains unclear which of the major immune players is the optimal target for a COVID-19 therapy. This is essential, since targeting the wrong immune players might even worsen the disease. Our main hypothesis is that the major detrimental immunological player is a specific population of pathological T cells and that selectively blocking these cells or their bioproducts, (e.g. cytokines, chemokines) will provide a cure for severe COVID-19 patients. We will use our established workflows to perform single-cell RNA-/ TCR-sequencing of lung-infiltrating leukocytes with a focus on T cells and parenchymal lung cells in severe COVID-19. The data analysis will reveal the functional heterogeneity of SARS-CoV-2-specific T cells and establish the pathological interactions between the immune cells and parenchymal lung infected versus non infected cells. Finally, we will test the function of the potential disease-driving cells and/or bioproducts using a recently established airway organoid system. The immediate impact of this project will be a COVID-19 immune atlas which will be key to choose the best target for the already available immune therapies to treat COVID-19 patients in the coming months.",2020,2021,Universitätsklinikum Hamburg-Eppendorf,496372.97,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06121,01KI20501,Legislative Authority in a State of Health Emergency (LegEmerge),"The saying that a state of emergency is the moment of the executive has, at least in Germany, become part of the public domain. Indeed, governments and administrations in Germany and around the world seem to be the decisive actors taking far-reaching decisions which aim at the control of the COVID-19-pandemic and, concomitantly, intrude into basic rights to a historically unparalleled extent. This provokes the question of what should be the legislator's role, especially within a parliamentarian system of democratic government as established under the German constitution. Therefore, this project aims at analyzing and defining the role of the legislator in a pandemic-induced state of health emergency. It will identify and evaluate the existing constitutional and statutory law framework governing a state of health emergency both on the federal and state level. In particular, the project will examine the constitutional limits to delegations of legislative powers to, and of authorizations conferred upon, the executive to take pandemic control measures. In addition, the applicability of the precautionary principle as well as its potential to justify the strict and sweeping measures of pandemic control will be investigated. Moreover, the project will elaborate on a constitution-based guidance for the legislator to enact rules framing triage decisions by clinicians. In light of these analyses, the project will propose options for a coherent and exhaustive legal framework for a state of health emergency as has been caused by the COVID-19 pandemic.",2020,2021,Universität Passau,175182.7,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C06122,01KI20533A01KI20533B,Life with Corona in Africa (LwC-Africa),"The overall objective of LwC-Africa is to generate new evidence and policy guidelines on how African citizens respond to and cope with the profound global shock to their lives and livelihoods caused by Covid-19. The LwC-Africa project builds on a unique Life in Corona online survey to advance understanding of how the pandemic is affecting health, food, work, gender and social cohesion outcomes to better prepare communities and governments to respond to the challenges ahead as the pandemic spreads across the continent. The LwC-Africa project will collect four quarterly repeated cross-sectional phone-based surveys over 12 months. The final choice of African case study countries will be made during the inception phase of the project. The objectives of the project are: - advance conceptual understanding of how a global pandemic impacts Africa - design research methods to generate rigorous evidence for pandemic - generate phone survey data on how people in five Sub-Saharan African countries are coping with the pandemic - analysis on the impacts of the pandemic - support policy actions to mitigate the effects of the pandemic The project will be implemented by a leading team of social and natural science researchers at two German research institutes and their international partners. The findings of this project will advance our understanding of the special challenges of coping with Corona in low income and fragile settings and will contribute to better policies and aid programmes to support the most vulnerable population groups in the vulnerable countries in Africa.",2020,2021,"Leibniz Institute of Vegetable and Ornamental Crops, International Security and Development Center",583812.64,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Gender,,,Germany | Germany,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +C06123,01KI20207,Modulation of SARS-CoV-2 Spike protein function by ADAM family proteases (MoCoSpA),"The SARS-CoV-2 spike protein interacts with angiotensin converting enzyme 2 (ACE-2) on epithelial cells in the lung which is a crucial step in viral infection and development of COVID2019. We propose that the metalloproteinases ADAM10 and ADAM17 are critical modulators of SARS-CoV-2 spike protein interaction with its receptor ACE-2 on lung epithelial cells. We want to study the induced release and functions of shed ACE-2 which may act as a soluble competitor and reduce the interaction of the virus with its membrane-anchored ACE-2 receptor. Moreover we want to study whether the spike protein triggers an inflammatory response by provoking increased ADAM-mediated shedding of proinflammatory mediators. These questions will be addressed in parallel by exposure of cultured epithelial cell lines and primary cells exposure to SARS-CoV-2 spike protein as well as by analysis of COVID19 patient tissues. For the analysis we will use established procedures to study ADAM activity, binding of adapter molecules, release of shed ACE-2, quantification of shed inflammatory mediators and cleavage of adhesion molecules. The analysis of these ADAM17 dependent responses shall help to understand why SARS-CoV-2 infection can cause a severe inflammatory response leading to ARDS with high mortality.",2020,2021,RWTH Aachen University,231146.99,Human Populations | Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C06124,01KI20123,Preparedness and Response for Ethical Challenges in Human Subject Research during COVID-19 and similar PandEmics (PRECOPE),"The WHO research roadmap for COVID-19 highlights as key priority to ""articulate and translate existing ethical standards to salient issues in COVID-19"". The PRECOPE study aims to address these needs by preparing for and responding to the practice-/decision-oriented challenges in translating ethical principles into concrete human subject research on COVID-19. In part 1 PRECOPE addresses the preparedness by summarizing current ethical challenges in COVID-19 research via literature reviews and interview research with relevant stakeholder groups. In part 2 PRECOPE addresses the response via the development of hands-on guidance for the 3-5 ""most-pressing/relevant"" ethical challenges. The selection of these challenges will again include the relevant stakeholder groups. The development process will include external experts (funded by work-contracts). Furthermore, part 2 will closely cooperate with the AKEK (Association of Medical Ethics Committees in Germany) representing all 52 German research ethics committees (REC). In part 3 we analyze and discuss with involved stakeholders and experts the SWOT (strengths, weaknesses, opportunities, threats) of all PRECOPE activities to inform future planning for COVID-19 like pandemics.",2020,2021,Charité - Universitätsmedizin Berlin,253603.13,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Research to inform ethical issues,Research to inform ethical issues in Research,2020 +C06125,01KI20434A 01KI20434B,Proteostasis as target for SARS-CoV-2 antivirals (ProteoCoV),"Therapeutic approaches against SARS-CoV-2 currently focus on repurposing of clinically approved drugs. Functional details on how these drugs affect SARS-CoV-2 are often unknown putting patient safety and clinical trials at risk. Our previous study on MERS-CoV revealed that autophagy, a mechanism for non-selective lysosomal protein degradation, is blocked by MERS-CoV infection. We now confirmed that SARS-CoV-2 also limits autophagy. Targeted induction of autophagy by clinically approved drugs reduced MERS-CoV and SARS-CoV-2 replication. Our preliminary data suggest that SARS-CoV-2 promotes selected degradation of proteins by activation of the ubiquitin proteasome system (UPS). We propose that SARS-CoV-2 modulates proteostasis by inhibiting non-selective autophagy while promoting selective proteasomal degradation. In the proposed project, we will perform pulsed-SILAC to analyze details of protein degradation processes upon SARS-CoV-2 infection on a proteome-wide scale. Identification, characterization and validation of candidate proteins and respective protein-targeting drugs will be done by established in silico, molecular and protein-biochemical techniques in combination with virological methods. Identified, clinically approved drugs will be tested by implemented in vitro methods to determine SARS-CoV-2 growth inhibition in non-toxic, nanomolar concentrations possibly encouraging clinical trials. The mechanistic insights into the virus host interplay will reveal novel, hypothesis-driven treatment and drug repurposing strategies against SARS-CoV-2.",2020,2021,"Universitätsklinik Bonn, Charité - Universitätsmedizin Berlin",589242.62,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C06126,01KI20539,Receiving and Accepting Public Information Despite Polarization: Key to Overcoming COVID-19 (RAPID-COVID),"RAPID-COVID is designed to produce insights about the information level about COVID-19 and the willingness to accept authoritative decisions to cope with the pandemic. The project is located at the intersection of political communication, political psychology, and political culture studies. We link research on media usage, campaign effects, populism and protest studies, to enhance our understanding how the information landscape interacts with individual predispositions to structure response patterns to the pandemic. Our aim is to provide insights into the processes at work - insights that can be rapidly used against the spread of the virus. We focus on six research questions: 1. Do citizens receive necessary and correct COVID-19 related information? Do they feel subjectively well informed and taken care of? 2. Do (problematic) differences in information levels exist between different segments of society? What are potential remedies to cure them? 3. How do citizens process information they receive? Which features of senders, messages, recipients, and contexts matter? 4. How widespread are feelings of discontent concerning measures to limit the spread of the virus? Does discontent grow over time? 5. What are the reasons for discontent? 6. Under which circumstances does discontent lead to non-compliance? To understand the distribution as well as the (causal) dynamics of COVID19-related information with respect to citizens, we propose to implement a three-wave longitudinal panel survey that is further enriched by survey experiments and paralleling cross sections.",2020,2021,Freie Universität Berlin,314840.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Social impacts | Other secondary impacts,2020 +C06127,01KI20337,Understanding the increased REsilience of Children compared to Adults in SARS-CoV-2 infecTion (RECAST),"In RECAST we will investigate whether the resilience of children compared to adults in SARS-CoV-2 infection is due to an age-specific immune response pattern. Our analyses involve multi-omics approaches using single cell RNA sequencing, mass cytometry on whole blood, high-throughput serum proteomics, serum- and saliva-based serology to reveal age-, respective disease-course specific classifiers of cellular composition and activation as well as mRNA and protein expression. We successfully applied these technologies in a collaborative approach within the PA-COVID-19 clinical trial and identified distinct response patterns between COVID-19 patients showing a mild versus critical disease course. Within RECAST this approach will be uniquely complemented with an ex-vivo analysis of nasopharyngeal epithelial cell responses playing a major role in mucosal barrier function. In addition to the infrastructure for data- and sample acquisition from hospitalized adults as part of the PA-COVID-19 study platform, RECAST benefits from vast network of participating pediatric outpatient practices and nursery schools providing access to a large number of children. RECAST will provide in depth understanding of protective immune responses in children and mildly symptomatic adults with COVID-19. We aim to identify new diagnostic biomarkers and therapeutic targets of COVID-19. In addition, the RECAST study will generate data on age-specific resilience factors, which may aide evidence-based decision making on social distancing and lockdown measures for childcare facilities and schools.",2020,2021,Charite - Universitätsmedizin,1829541.47,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +C06128,01KI20328A 01KI20328B,Repurposing nafamostat mesylate for COVID-19 treatment (RENACO),"The novel, pandemic coronavirus (SARS-CoV-2) and the associated disease COVID-19 threaten public health and economies worldwide. In the light of a constantly rising death toll, drugs are urgently needed. The only way to meet this need is to repurpose drugs that have been approved for treatment of other diseases. We have recently shown that the cellular serine protease TMPRSS2 is essential for SARS-CoV-2 infection of lung cells and that a clinically proven TMPRSS2 inhibitor, camostat mesylate, blocks infection. Our recent results show that the FDA-approved serine protease inhibitor nafamostat mesylate, which is used in Japan for treatment of pancreatitis, has 50-fold higher antiviral activity as compared to camostat mesylate. The goal of the present study is to develop nafamostat mesylate for treatment of SARS-CoV-2 infection. For this, we will pursue three goals: First, as proof-of-concept, we will determine the antiviral activity of nafamostat mesylate in a non-human primate (NHP) model of SARS-CoV-2 infection. For this, the compound will be applied intravenously, the route of application used in pancreatitis patients. Second, we will analyze whether the compound can be nebulized and safely applied to the airways. For this, safety and pharmacokinetic studies of the inhaled drug will be conducted in rats and ex vivo lung tissue. Third, we will determine whether application of nafamostat mesylate to the upper respiratory tract of NHP as spray inhibits SARS-CoV-2 spread and could be used for prevention of COVID-19.",2020,2021,"Deutsches Primatenzentrum GmbH, Göttingen, Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.",1894738.48,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06129,01KI20391,RTK structure - structure and function of the non-structural proteins in SARS-CoV-2 replication and transcription complexes (RTK-Struktur),"The overall goal of the project is to transfer our work on SARS-CoV non-structural proteins (NSP) to SARS-CoV-2. For this purpose, all NSPs that are not membrane-bound should be expressed both in bacteria and in eukaryotic systems. Subsequently, partial complexes of the replication and transcription complexes (RTK) should be assembled from the purified NSP and checked for their functionality, e.g. RNA binding and processing. After characterization with native mass spectrometry (MS), selected complexes are to be fed into functional assays and structural biological methods with higher resolution in order to obtain a better understanding of virus biology. This application relates to the announcement ""Funding call for research into COVID-19 in the course of the Sars-CoV-2 outbreak of 03.03.2020"". According to the announcement, the subject of funding is to investigate the biology of the virus. The work is carried out as part of Module 4 - Support for ongoing research projects on coronaviruses - and extends the ERC Starting Grant ERC-StG-2017 759661 ""SPOCk'S MS - Sampling Protein cOmplex Conformational Space with native top down Mass Spectrometry"". The goals are as follows: - Expression of the SARS-CoV-2 NSPs - Assembly of protein complexes of the RTKs - Structural and functional study of the complexes obtained",2020,2021,"Heinrich-Pette-Institut, Leibniz-Institut für Experimentelle Virologie",58500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06130,01KI20511A01KI20511B,Solidary Attitudes and Actions in the Covid-19 crisis as a Trade-off to Freedom and Economic well-being (SAFE-19),"The governments' mitigation measures to fight the COVID-19 pandemic are unprecedented in our post-war history. Citizens are expected to act in solidarity in order to control the spread of the virus and keep public health systems functional. They are called to cope with confinement, limitations of their freedom and economic activity. SAFE-19 provides a social sciences perspective on the concept of solidarity which has become a central claim for the fight against COVID-19. We divide the pandemic into three phases a) mitigation phase b) stabilisation phase and c) the new equilibrium. SAFE-19 strives to shed light on two major questions. What are the sources and scope of solidarity when society as a whole is faced with nearly impossible trade-offs? What are the conditions that enable a political community to act in solidarity and support solidary measures? Focusing on Germany between January and December 2020, we utilise a mixed methods approach: policy coding, survey data, discourse analysis of speeches, and twitter corpora including billions of tweets in order to offer a precise picture of solidarity in Germany in the context of COVID-19 and the trade-off between self-interest and common good orientation. SAFE-19 will demonstrate the ups and downs of solidarity in the intersection between politicians and citizens, and will offer insights to policy makers and other societal stakeholders on the fragile nature of solidarity in settings with extreme trade-offs between freedom and economic well-being on the one hand and saving human lives on the other.",2020,2021,"Universität Hildesheim, GESIS - Leibniz Institut für Sozialwissenschaften, Köln",522082.29,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Communication | Policy research and interventions",2020 +C06131,01KI20396,Significance of the optimized S1 / S2 restriction site for SARS-CoV-2 infection (SARS_S1S2),"As part of the already funded coronavirus project (BMBF-Verbund RAPID: Risk assessment in prepandemic respiratory infectious diseases, subproject 4: Efficiency of the proteolytic activation of respiratory viruses as a marker for pandemic potential), it is investigated whether naturally occurring MERS-CoV variants represent an increased pandemic Show potential. A virus variant was identified in patients in Saudi Arabia that carries the T746K exchange at the S1 / S2 interface of the viral spike protein (S). This exchange leads to the fact that the cleavage of the S protein at the S1 / S2 interface is intensified by the cellular protease furin in infected cells. Also increased the exchange of virus entry into lung cells, which depends on the activation of the S protein by the cellular protease TMPRSS2. Finally, the exchange increases the resistance to the interferon-induced host cell factors GBP2 and GBP5. To what extent T746K increases the virus spread in primary lung epithelium in vitro and the viral spread and pathogenesis in experimentally infected marmosets is unclear and is being investigated in the ongoing project.",2020,2021,Deutsches Primatenzentrum Gesellschaft mit beschränkter Haftung- Leibniz-Institut für Primatenforschung,58159.53,Animals | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2020 +C06132,01KI20158,SARS-CoV-2 und das antivirale Interferonsystem (SARS2_IFN) [Google Tranlate: SARS-CoV-2 and the antiviral interferon system (SARS2_IFN)],"Type I interferons (IFN-alpha / beta) and other cytokines represent the first line of defense against viral infections. IFN activates the expression of more than 300 so-called ISGs (IFN-stimulated genes), some of which are able to deliver viruses directly inhibit. Pathogenic viruses often prevent the induction of IFN, block the signaling triggered by IFN or specifically inactivate individual ISGs. They can also trigger the induction of pro-inflammatory cytokines. The quality and strength of IFN and cytokine induction, IFN evasion, and IFS sensitivity, collectively known as the Innate Immunity phenotype, is an important marker of virulence. The aim of our subproject is to establish systems for the detection of the Innate Immunity phenotype of pre-pandemic respiratory viruses in order to be able to carry out a rapid risk assessment. For this purpose, we will measure the activation of cytokines (including IFN) and antiviral ISGs and create an IFN sensitivity profile for each virus examined. In addition, we will generate a library of ISG-expressing cell lines in order to identify specific ISG resistances and sensitivities. The now largely established systems are now to be applied to the new SARS-CoV-2.",2020,2021,Justus-Liebig-Universität Gießen,57052.89,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +C06133,01KI20154,Aptamers directed against the SARS-Cov2 S protein (SARS-Cov2-Aptamers),"This proposal aims at isolating nucleic acid aptamers (ssDNA, 2'-F-RNA, clickmers) directed against the SARS-Cov2 S protein, and capable of blocking the binding of the virus to the ACE2 receptor. We will use the prefusion-stabilized S ectodomain (AA 1-1208) of the SARS-Cov2 S protein, described in Wrapp et al (2020), for which we have the respective expression plasmids. We will perform parallel SELEX en-richments of chemically stabilized aptamer libraries using our in-house automated selection platform. Moreover, we will also carry out a click-SELEX to enrich for clickmers. Besides in vitro binding assays to quantify the interaction of SARS-Cov2 S with ACE2 in presence of the isolated aptamers we will collaborate with virologists who will test the performance of the aptamers in infection studies in cell culture, and in virus replication assays. Anti-Cov2 S aptamers will be converted into rapid test assays (ELONA, Lateral Flow Assay, dip-stick assays) and will be further developed as therapeutics, e.g., in preventive protection sprays.",2020,2021,Rheinische Friedrich-Wilhelms-Universität Bonn,700950.95,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pre-clinical studies | Prophylactic use of treatments",2020 +C06134,01KI20210,Highly specific IgM and IgG ELISA tests for detection of anti-SARS-CoV-2 antibodies in human sera (SARS-CoV-2-Serologie),"In the context of the current COVID-19 pandemic, sensitive and specific serological tests for the detection of SARS-CoV-2-specific antibodies in human sera are a mandatory prerequisite for epidemiological studies, the retrospective evaluation of molecular testing sensitivity and the performance of vaccine studies. Furthermore, the economic and social burden of shutdowns and social distancing could be alleviated by securely identifying individuals having developed SARS-CoV-2 immunity. Due to the existence of several other human pathogenic Corona viruses, a considerable percentage of false positive test results caused by cross-reactive antibodies can be expected if conventional tests methods (e.g. indirect ELISA or IIFT) are applied. Therefore, the Bernhard Nocht Institute for Tropical Medicine (BNITM, Hamburg) aims at developing a highly sensitive and specific SARS-CoV-2 ELISA employing a patented ELISA technology (EP2492689, EP3207375) that allows efficient suppression of cross-reactive signals and has already been successfully applied to a similarly challenging task, i.e. serological differential diagnosis of flavivirus infections. Following test validation using a comprehensive collection of well characterized COVID-19 patient samples (including longitudinal serum samples allowing observation of seroconversion in individual patients) and negative control sera, an independent comparative evaluation of the newly developed tests will be performed in cooperation with the Foundation for Innovative New Diagnostics (FIND).",2020,2021,"Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Hamburg",582524.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06135,01KI20510,Solidarity in times of a pandemic? A comparative longitudinal study on values and behaviours (SolPan),"The COVID-19 pandemic poses unprecedented challenges for policymakers, public health officials, and societies. The social and economic effects are likely to be felt for years to come. Solidarity has been frequently referred to in designing pandemic response measures; however, little is known about whether, and if so how, solidarity is a value that informs people's behaviours and what other values might play a motivational role. As part of the SolPan consortium of nine European countries, this project aims to explore how people react to and evaluate policy measures that have been introduced in Germany and the German-speaking part of Switzerland. Further, the project evaluates whether, and if so how and why people accept, resist, or take additional actions of their own initiative beyond the official advice by governments. The goal is an in-depth examination of these questions using a mixed methods approach. The study will be conducted in two phases, comprised of qualitative research methods in the first phase (semi-structured interviews), followed by a quantitative element (development and completion of a large-scale, representative survey) in a second phase of the study, in two German-speaking cohorts. Results will be discussed for their national implications and compared with findings from the other countries in the consortium.",2020,2021,Technische Universität München,178594.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany | Switzerland,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C06136,01KI20347,"Influence of the Sars-CoV-2 epidemiology due to co-infections with helminths in Ghana. BMBF research networks for health innovation in sub-Saharan Africa financed the project ""Removing the barriers to fighting v. Filariasis & Podoconiosis ""(TAKeOFF No. 01KA1611)","SARS-CoV-2 breitete sich weltweit aus, auch in den afrikan. Ländern. Im Gegensatz zum hohen Prozentsatz der Todesfälle, z. B. 5,5% in den USA, war er in afrikan. Ländern niedriger, z. B. 0,7% in Ghana. Während Ghana über weniger Ressourcen verfügt, um Tests durchzuführen, erklärt dies die niedrigeren Sterblichkeitsraten nicht vollständig. Es ist bekannt, dass Helmintheninfektion, die Immunantwort immunmodulieren, so dass auch die Reaktion auf unspezifische Reize unterdrückt wird. Darüber hinaus zeigten mehrere Studien, dass Helmintheninfektion die Inzidenz und den Schweregrad von Virusinfektionen beeinflussen, aber wie sich die Koinfektionen gegenseitig beeinflussen, ist unbekannt. Daher ist es dringend erforderlich, den Einfluss der Helminthen-Koinfektion auf COVID-19 zu untersuchen, insbes. in Afrika. Als Reaktion auf die Ankündigung der BMBF-Finanzierung für die Forschung zu COVID-19 vom 3.3.20 haben wir eine epidemiologische Studie entworfen, die unser vom BMBFForschungsnetzwerk für Gesundheitsinnovation in Subsahara-Afrika-finanziertes Projekt ""Bewältigung der Hindernisse zur Bekämpfung von Filariose und Podokoniose ""(TAKeOFF, Nr. 01KA1611;) ergänzen wird. Die Studie wird die Seroprävalenz der Coronavirus-Infektion in einem abgelegenen Gebiet in Ghana liefern, aus dem ansonsten jedoch nur wenige Daten vorliegen, und einen Zusammenhang zwischen Helmintheninfektion und dem Schutz gegen Covid-19 herstellen sowie eine Biobank zur Verfügung stellen. Daher werden wir 1) die Seroprävalenz von COVID-19 in Kassena Nakana, Ghana, und 2) die Koinfektion mit Helminthen und COVID-19 bestimmen. Dies wird zeigen, wie die Teams aufgrund vorherigen Kapazitätsaufbaus innerhalb von TAKeOFF schnell auf einen neu auftretenden Krankheitserreger reagieren und epidemiologische Daten bereitstellen können, die für Entscheidungsträger in Ghana nützlich sind. Die Ergebnisse werden auch dazu beitragen zu erklären, wie Helmintheninfektion den Schweregrad von Covid-19 verringern können.",2020,2021,Rheinische Friedrich-Wilhelms-Universität - Universitätsklinikum Bonn,56139.22,Human Populations,Black,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Africa | Europe,,,,Germany,Ghana | Germany,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis,2020 +C06181,NIHR132046,Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN),"Background: Many survivors of novel coronavirus infections (SARS-Cov and MERS-Cov) had substantial physical, psychological and neurological morbidity for up to 12 months. Similar longer-term consequences of COVID-19 are now apparent. Case level mental health diagnoses along with disabling fatigue, breathlessness and muscle weakness are commonly reported. There is a large population of COVID-19 survivors in the UK with persistently reduced quality of life, even after several months of recovery. Exercise and psychological rehabilitation may help but existing NHS rehabilitation services have insufficient capacity. Alternative delivery models must be tested. Design/setting: Two-arm multi-centre RCT with parallel process evaluation and 1-month internal pilot (n=35). Treatment allocation of 1:1.03 randomised by minimisation based on age, assisted ventilation, and case level mental health disorder. Population: Adults recovering from COVID-19, more than 3 months after hospital discharge with continued physical and/or mental health sequelae, and access to internet video. Exclusions are exercise contraindications and severe mental health problems preventing engagement. Health Technology Assessment: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN' (REGAIN) intervention is an eight-week, on-line, supervised, home-based, exercise rehabilitation programme with behavioural, motivational and mental health support. REGAIN includes: 1) individual assessment; 2) supervised home-based exercise programme with pre-recorded and live sessions; 3) one-to-one and group on-line psychosocial and motivational support and education. Control: Single, on-line, one-to-one, practitioner consultation with general advice on safe and effective physical activity. Outcomes. All measures completed on-line at baseline and 3 (post-intervention), 6- and 12-months post-randomisation. Primary: PROMIS® 29+2 Quality of Life questionnaire at 3 months. Secondary: dyspnoea, EQ-5D-5L, anxiety/depression, PTSD symptom severity, cognitive function, work status, physical activity, health and social care use, cost-effectiveness. Sample size: Allowing for 10% loss to follow-up, 535 (263 control, 272 intervention) participants are required to achieve 90% power at 5% significance level; based on standardised mean effect size of 0.3 (i.e. three points), intervention group size of 8 and an intra cluster coefficient of 0.01. Analysis. Summarised/reported as per CONSORT, using intention-to-treat analyses. Treatment effects (with 95% CI) estimated with hierarchical linear regression models, adjusted for patient-level covariates. We will estimate and adjust for site effects as a random variable in the model. Categorical data analysed using logistic regression models. Pre-specified, exploratory sub-group analyses will examine the interaction of treatment assignment. Prospective cost-effectiveness assessed as incremental cost per QALY estimates and credible intervals, cost-effectiveness acceptability curve and value-of-information analyses. Team: Lay partners, ICUsteps charity, clinical exercise physiology, physiotherapy, health psychology, psychiatry, critical care and respiratory medicine, general practice, statistics, health economics, clinical trialists. Timeline (month): set-up (0-1); internal pilot (2-3); recruitment (2-9); primary outcome (5-12); analysis/dissemination (13-14), 6-month follow-up (8-15), 12-month follow-up (15-22).",2020,2022,University Hospitals Coventry & Warwickshire NHS Trust,1549570.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +C06182,NIHR132068,Work-related stress: the Impact of COVID-19 on Critical Care and Redeployed Nurses,"Background: Critical care nurses (CCNs) and nurses deployed to critical care areas experienced significant challenges during the pandemic. They were faced with a multitude of difficult and new demands, including the high acuity and associated mortality rate of COVID-19 patients, the need to deliver care using personal protective equipment, to communicate and support relatives at a distance, and the well-publicised potential risks to personal and family health. There is a need to understand the impact of these increased demands at the individual, unit and organisational levels in order to know how best to support staff now and through possible second and third waves of the pandemic. This 2-phase, mixed methods study will use a theoretical model of occupational stress, the Job Demand Resource (JD-R) model to understand the impact of the COVID-19 pandemic on CCNs and staff deployed to critical care areas. The JD-R model specifies individual factors (personal resources e.g. resilience), work environment and job characteristics (job demands (e.g. workload) and job resource (e.g. autonomy)) variables that may lead to either negative (health impairment, reduced job satisfaction, burnout) or positive (work engagement, commitment) outcomes for staff, and organisational outcomes (intention to remain and quality of care). Phase 1: Questionnaire study: All CCNs employed within NHS ICUs in 20 adult critical care units across Scotland and three units in England (around n=2000) and registered nurses who were redeployed to critical care areas on at least 2 occasions will be invited to complete a questionnaire designed to measure all components of the JD-R model of stress. We have a recently completed study that employed the JD-R model to assess stress in CNNs prior to COVID. This study will act as baseline data for the current study. Structural equation modelling analyses will be used to assess the ability of the JD-R model to account for the data. These analyses will identify the sources of stress that impact on individual wellbeing and organisational outcomes, such as intention to remain in post. It will also identify factors that mitigate the impact of stress on individual and organisational outcomes. Phase 2: Qualitative Interviews: in depth interviews with CNNs and redeployed nurses (up to 35 interviews with a stopping criterion) will explore the challenges and consequences of delivering critical care services during the pandemic and information about the support services they were offered, used and found useful will be recorded. Framework analyses will be applied to the data with the JD-R model providing the initial codes for charting. Interview text that remains after extraction of the JD-R coded text will be analysed using the usual framework method. The use of the same theoretical framework for the quantitative and qualitative components of the study will facilitate integration of results across phase 1 and 2 of the study. Information about the support services offered, used and found useful by staff will be compared to the sources of stress and the factors that mediate or moderate the effect of stress on health and wellbeing identified in phase 1. Understanding the match and/or mis-match between stressors and support services provided will identify services to be retained, services that are candidates for discontinuance and areas of unmet need.",2020,2021,University of Aberdeen,239937.58,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C06183,NIHR132041,"Lessons from the frontline: The impact of redeployment during Covid-19 on nurse well-being, performance and retention","Background: Delivering safe and effective healthcare requires sufficient staff numbers with the right skill mix. Thus, the rapid redeployment of nursing staff has been critical to the NHS response to COVID-19. The NIHR have recognised the significance of these changes and the challenges of rapidly reallocating staff without evidence on how best to do this or what the longer term consequences are. This proposal directly addresses this evidence gap (see NIHR COVID-19: Recovery and Learning call), falling squarely within the HS&DR remit. Senior NHS Trust staff had to plan staff redeployment in a short timescale with no existing guidelines and had to do this again when certain groups of staff (e.g. BAME) were identified as high-risk. The redeployment of frontline nursing staff has been varied. Some were redeployed to work in high risk areas, others to non-patient facing roles (Dunn et al, 2020). Many worked in unfamiliar teams, caring for frightened patients, dealing with inadequate PPE, and fearing virus transmission. While the psychological consequences of working through COVID-19 are emerging (Nursing Times, 2020), there is no empirical research examining the impact of redeployment on UK nurses. This research addresses two aims 1) understand the impact of redeployment during COVID-19 on nurse well-being, performance and retention 2) provide guidance for those responsible for redeployment at national and local level. Due to the possibility of local 'spikes'/second waves of COVID-19, this work will be of huge value in the on-going management of the NHS workforce in the current pandemic. As redeployment has become common for nursing staff, this work is also directly applicable to improving healthcare during normal service delivery. We will work with 3 NHS Trusts: Oxford, Royal Free and Bradford (all agreed). The multi-disciplinary research team, led from one of the 3 NIHR Patient Safety Translational Research Centres, has the expertise and experience to deliver this project. Close collaboration with a nurse advisory panel and two lay leaders will support the delivery and dissemination of the work. We will also explore the role of the public and patients via our citizen participation group. Two work-packages(WP) will achieve the programme aims as follows: WP1: How was the process of redeploying nursing staff managed prior to and during the Covid-19 crisis? Method: Interviews with 30 senior nurses and 3 senior HR managers responsible for decision making. One senior nurses focus group per Trust. WP2: How did nurses make sense of redeployment during the COVID-19 crisis and what effects does it have on well-being and job outcomes? Method: Questionnaires and interviews at 3 time points with 50-60 nurses involved in different forms of redeployment across the 3 Trusts. Further to these work packages we will work with stakeholders to develop recommendations and guidance based on our learning about how best to manage redeployment and support staff reallocation in future waves of Covid-19 and routine service delivery. We will disseminate our findings to academic (e.g. organisational behaviour and patient safety) and professional (e.g. nurse managers, HR managers) audiences through publications and conferences/meetings.",2020,2022,Bradford Institute for Health Research,365766.83,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2020 +C06184,NIHR132197,"CONtact TrAcing in Care homes using digital Technology (CONTACT) - A pragmatic cluster randomised controlled trial, cost-effectiveness evaluation and theory-informed process evaluation.","Background: 400,000 people live in ~115,000 care homes with and without nursing. With no COVID-19 vaccine, 80% infection and 50% mortality rates in some homes, testing and crucially - contact tracing must become business-as-usual in homes for effective infection control, mortality reduction and minimising community transmission. Traditional contact tracing in care homes is ineffective: ~70% of residents have a cognitive deficit/dementia making reliable recall unfeasible and care staff would need to recall >50 contacts a day. Interview and document-based tracing is labour intensive, expensive and extremely burdensome. Small, wearable, inexpensive, digital devices within secure 'plug and play' wireless networks in homes can provide reliable real-time and historic contact data. Wearables can increase the quantity and quality of contact data, with almost zero burden, using technologies similar to those already present in homes: access fobs, cards and wristbands. The information produced can help homes plan and evaluate infection control procedures such as cohorting of residents/staff, environmental zoning and modification. Systematic reviews of care home infection control suggest 30% improvements in mortality are possible. Research question: Are wearable digital contact tracing devices and tailored feedback of results (the CONTACT intervention) a cost-effective means of contact tracing in care homes, improving infection control and COVID-19 resident infection rates and reducing mortality, compared with contact tracing as usual in homes (the controls)? Research design: pragmatic cluster randomised controlled trial with embedded cost effectiveness analysis, and theory-informed process evaluation. Methods: Over 12 months, residents, staff and visitors in 64 care homes - (80% power to detect a 25-40% improvement in infection rates) in Yorkshire and Midlands will be randomised to the CONTACT intervention or control arms. After brief training for staff and base station installation, CONTACT will provide real time and retrospective data to each home and NHS test and trace services on all individual-individual and individual-home environment contacts (e.g.kitchens,corridors) in homes. Tailored information on contact patterns and trends, including frequency and constituents of contact(s), environment 'pinch points', and deviations from infection control procedures (cohorting/zoning) will be fed back monthly as an emailed PDF and via an electronic dashboard website for each home. Economic data on costs and resource use will be analysed and expressed as £-per-infection-avoided and willingness-to-pay. Determinants for embedding the CONTACT technology will be explored using a mixed method (QUANT|QUAL) process evaluation based on Normalisation Process Theory. Primary analysis of clinical effectiveness will be differences in infection rates (+PCR swab test) and all-cause mortality. Impacts: CONTACT will enable care homes to plan and evaluate infection control procedures efficiently, increasing the likelihood of lower mortality from COVID-19. CONTACT will provide data otherwise unavailable to the NHS Test and Trace system, ensuring contact data does not start and finish at the care home door . It will facilitate more and safer visiting, constructive conversations between homes and the NHS regarding viral transmission risks and offer a minimal-burden approach for care homes to contribute to reducing the impact of COVID-19 on communities.",2020,2023,University of Leeds,2018103.23,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C06185,NIHR132541,Protecting older people living in care homes from COVID-19: challenges and solutions to implementing social distancing and isolation.,"Research for Social Care Programme Care homes (CHs) provide care for some of the vulnerable population of older people. They are at high risk of poor health outcomes and mortality if they contract COVID-19. The risk of contracting COVID-19 is compounded by difficulties in implementing infection control measures such as social distancing and isolation of residents. It is critical that CH services remain safe and provide high quality care during the pandemic and for further surges. Our research will provide a unique contribution to helping protect older people living in CHs from COVID-19. Research aim: to explore and understand the real-life experiences of social distancing and isolation in CHs for older people from the perspective of multiple stakeholders, and to develop a toolkit of evidence-informed guidance and resources to support health and care delivery now and for further outbreaks. Design: This tripartite 12-month study involves a rapid evidence review, in-depth case studies, and toolkit development. Methods: Phase 1: A rapid review of evidence to collate knowledge on the mechanisms and measures used by CHs and long-term facilities previously to socially distance and isolate older people or control the spread of other infectious and contagious diseases. Phase 2: a) In-depth case studies of 6 purposively selected CHs to identify the real-life challenges and consequences of providing safe care incorporating social distancing and isolation measures and to identify novel solutions being used to implement these measures in a person-centred way. Data collection: Within each CH case study: Interviews with a purposive sample of 3 residents and 3 family/friends to examine their experiences while residents are social distancing and isolating. Interviews with a purposive sample of 5 staff to examine how they adapt and manage care delivery for residents with different needs whilst maintaining social distancing and isolation of residents. Interview with the CH manager/deputy to examine how they develop, manage, and adapt policies, procedures, and protocols to achieve these measures. Collection of relevant documents and routinely recorded CH data to understand contextual factors. 2b) A focus group with a purposive sample of 8 external key informants with macro-level knowledge and experience relevant to the pandemic for the CH sector. Data analysis: Interviews will be transcribed and analysed using thematic analysis. Documentary data will be analysed using thematic analysis. Concurrent data collection and analysis will inform decisions about the need for further data collection. Analysis for each case site and across case sites will be conducted. Descriptive summary statistics will be used to describe quantitative data. Phase 3: Synthesis of findings from Phases 1 and 2 will culminate in a co-produced toolkit comprising evidence-informed guidance and resources. The content of the toolkit will be presented in different ways e.g. using flow charts to present evidence-informed guidance, and film to help narrate the stories of older people, their families/friends and CH staff. We will work with CH practitioners, our CH co-applicants, our PPI group, and Project monitoring and advisory group to co-produce a final version that is meaningful, accessible and will be used in practice. Dissemination: project website; publication in peer-reviewed, professional journals, and sector press; social media; presentations to different audiences.",2020,2021,King's College London,308176.44,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +C06186,NIHR131747,Support and enabling health research in local authority: an exploratory study (SERLA),"Research question: What are the factors, relationships, and processes that contribute towards generating research evidence that is of relevance to local public health and shapes its practice? Background: In 2013, the public health function was transferred to Local authorities (LAs) with the responsibility for improving population health and reducing health inequalities. In a time of austerity, LAs need high-quality evidence to optimise the use of resources and implement effective changes to improve population health. Conducting effective transdisciplinary research is vital for tackling future public health challenges. LAs are suitably placed to create transdisciplinary teams due to the broad range of council functions influencing the wider determinants of health. LAs could play a key role in generating their own evidence-base by evaluating public services but the lack of resources and sustainable support infrastructure prohibit the development of rigorous evaluations and making them part of normal practice. The NIHR invest considerable funding to support NHS research and is keen to develop an infrastructure enabling LAs to become research active, but there is little evidence about what works within a LA environment. To fill this gap in knowledge, we will use two major public health challenges as exemplars which aims to provide insight into one LA (Southampton City Council, termed Southampton LA hereafter) public health response in relation to standard practice (childhood obesity) and a crisis (COVID-19). We will identify key mechanisms for generating and using research evidence within a LA environment to support the development of a research system to inform future public health actions. Methods: A qualitative study design will address the study aims using semi-structured interviews with a range of staff across departments in Southampton LA and community members. An interview guide will be developed to allow participants to reflect on responses to public health challenges. This considers the key people, organisations, concerns and other factors that influenced these responses, their views on the enablers and barriers for LA research, the use of research evidence in daily practice, and recommendations for a LA focused research system. A separate interview guide will be used for community members to explore current engagement and involvement with LA services. Due to the COVID-19 pandemic, interviews will be conducted using online platforms such as Zoom or by telephone. Interviews will be audio recorded, transcribed verbatim and analysed using thematic analysis. Timelines for delivery: The study is expected to commence in June and end in September 2020, with a written report due October 1st. However, restrictions placed on LA activity due to COVID-19 mean that these timelines may need to be revised. Anticipated impact & dissemination: This study will provide comprehensive insights into LA actions in tackling public health challenges and the resources needed to create a research system across health and care systems within a LA. We will co-ordinate and host a national stakeholder event to disseminate what we have learned from Southampton LA and present findings at the Local Government Association (LGA) and Public Health England (PHE) conferences. We will also share our findings with local and national Public Policy colleagues across academia and PHE",2020,2020,University of Southampton,54357.2,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Policy research and interventions | Institutional level capacity strengthening,2020 +C06187,NIHR132269,"The Resilience Hubs: A multi-site, mixed-methods evaluation of an NHS Outreach, Screening and Support Navigation service model to address the mental health needs of key workers affected by the COVID-19 pandemic","BACKGROUND: A healthy and resilient NHS and social care workforce is essential to ensure an optimal response to both the current pandemic and future large-scale crises. Research indicates that key workers are at high risk for both acute and long-lasting mental health issues as a result of the adversities faced during the pandemic. The NHS Clinical Leaders Network (2020) has issued an urgent call for action to ensure that NHS organisations prioritise initiatives to enhance mental health resilience and support provision for key workers during this time. The Lancet Psychiatry's immediate research priorities for the COVID-19 pandemic (Holmes et al. 2020) include monitoring mental health issues and determining the best ways of signposting and delivering mental health services for vulnerable groups, including key workers, and to identify and provide interventions to promote mental wellbeing in key workers exposed to stress and trauma that can be delivered now and at scale. RESEARCH AIMS: This research will evaluate the Resilience Hub model in three UK sites. The Resilience Hub is a service model originally developed in response to the 2017 Manchester Arena bombing. It has been adapted and repurposed in Greater Manchester to provide mental health screening and facilitation of access to evidence-based psychosocial support for NHS, social care and emergency response key workers throughout the COVID-19 pandemic. The model is being replicated to support mental health needs of key workers in other UK regions. METHODS: The research will take 20 months. We will produce mixed method case studies triangulating findings from 1) quantitative analyses of routine mental health screening data collected at the three Hubs; 2) health economic analyses conducted using Hub clients' service use and health status data; 3) in-depth interviews with Hub providers (recovery workers; therapists; service managers; commissioners), and key workers who did and did not register with the Hubs. The project will deliver crucial data and evidence-based recommendations for ensuring the 'transactability' of the Hub approach (i.e. how it can be scaled up and replicated in other sites in the UK) and inform evidence-based commissioning both in the short-term (in response to the ongoing pandemic) and longer term (in response to future large-scale crises). These include: i) data relevant to the identification of subgroups of key workers with higher support needs and/or lower support uptake, to guide effective targeted outreach and model service demand; ii) recommendations for maximising mental health screening uptake and psychosocial support access and uptake following screening; iii) guidance on resolving systemic and organisational barriers to accessing onward psychosocial support; iv) economic data to inform future commissioning decisions.",2020,2022,Greater Manchester Mental Health NHS Foundation Trust,616694.78,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C06188,NIHR129678,Primary care Networks,"Background In its 2014 Five Year Forward View, NHS England (now NHS England and Improvement) identified the need for new models of care to improve collaboration across health and social care services. This plan suggested that GP practices work together (and with other primary care providers) in a more systematic, sustained and organised manner. As a result, primary care networks were introduced in 2019 to bring together groups of general practices to hold shared budgets through a collective contract, and develop new and more integrated services. Hence, primary care networks have a formal, incentivised and almost compulsory feel compared to many predecessor schemes of collaborative primary care. There were (in May 2020) 1259 primary care networks in England, serving populations ranging from 20,000 to well above the 50,000 suggested in national guidance. Networks sometimes build on prior GP collaborations such as super-partnerships or federations, which can provide organisational infrastructure and support to newly formed networks. However, some primary care networks also bring together practices that had not worked collaboratively in the past. Objectives The purpose of this evaluation was to produce early evidence of the development and implementation of primary care networks. We sought to answer these research questions (RQs): RQ1: What was the policy context within which primary care networks were introduced? RQ1.1: What were the pre-existing forms of GP collaborative working across primary care in England? RQ 1.2: How have new networks been implemented in a sample of urban and rural settings? RQ 1.3: How do new primary care networks relate to pre-existing GP collaborations? RQ2: What was the rationale and motives for general practices to enter into new primary care networks? RQ3: What evidence exists about the impact of establishing GP collaborations and how does this relate to primary care networks? RQ4: What are the barriers to and facilitators of effective collaboration across GP practices? RQ5: What does this evidence suggest in terms of the likely progress of primary care networks in the NHS in England, including in light of the Covid-19 pandemic? Methods A mixed methods cross-comparative case study evaluation with four case study sites, comprising four work packages (WPs): WP1: Rapid evidence assessment: We conducted a review of published evidence on GP collaborations to inform the design of our evaluation. This included English-language evidence summaries (published from 1998-2012) and primary care research studies and reviews (published from 2013-2018), using key search terms in titles and abstracts in PubMed, Ovid MEDLINE, Web of Science, and Scopus. WP2: Stakeholder workshop: We held a workshop with academics, policy experts and patient and public involvement representatives, to explore findings from the rapid evidence assessment. This enabled us to clarify evidence gaps and develop evaluation questions for WP3. WP3: Comparative case studies of four primary care networks: We undertook multi-faceted sampling to select four rural and urban case study sites. Interviewees (N=25) were purposively sampled and asked about the primary care network, its implementation, facilitators, barriers and early impact. We collected data through: analysis of key documentation; non-participant observations (N=10) of strategic meetings; and an online survey (N=28) of network staff. We used content analysis for documentary reviews and observations, and framework analysis for interview data. The Covid-19 pandemic caused data collection to cease earlier than planned. WP4: Analysis and conclusions: We synthesised our findings to develop suggested lessons for commissioners, providers and policy makers about the future development of primary care networks. Results The rapid evidence assessment identified important lessons for primary care networks, including the time required for networks to become properly established, and the level of high-quality management and leadership capacity required for success. The review also revealed the wide range of formal and informal collaborations across English primary care, and their importance as context for the implementation of primary care networks. Key themes from our data analysis were: Purpose of primary care networks Leaders of primary care networks support the overarching policy aims, and general practices across England have seized the opportunity to access new funding to form networks. Although keen to improve service integration, primary care networks often prioritise the sustainability of general practice, addressing workload pressures, and improving the availability of local primary care services. Primary care networks are expected to meet local population health needs, whilst meeting nationally-specified requirements to employ certain professionals and introduce defined services, which was a source of tension for the primary care networks in our evaluation. Prior GP collaborations In all four case studies, the new primary care network was established in the context of a prior GP collaboration. These helped the networks build on previous successes such as strong relationships between practices and integrated service delivery. Prior collaborations often provided the new network with additional operational and management support. There were also some tensions where the new network was perceived as un-doing the work of the previous collaboration, where aims of the two organisations did not align, or where practices from two previous collaborations joined a single network. Engagement in primary care networks This evaluation revealed a tension between the desire for local autonomy within primary care networks, and the top-down nature of national PCN policy. This led to some differences between local and national priorities, and struggles with local clinical commissioning groups. Networks were therefore aware of the need to take time to clarify roles of primary care networks within the local health system, and develop shared goals and objectives within the network itself. Time and resource for organisational development were important for this process, including through staff away days, and joint training events across the primary care network. Leadership and management The need for effective leadership and management support for primary care networks was a strong theme in the evaluation, particularly the capacity required for implementing and managing networks (e.g. for meetings, recruitment of staff, implementing new services). Time pressures for those leading network development was reported as an acute concern, especially for clinical directors and practice managers. The range of leadership and management expertise on the part of network clinical directors raised a concern about the sustainability of these roles longer term. Funding and incentives A consistent message was that primary care networks had been established in a near universal manner due to NHS England and Improvement using them as the mechanism to offer significant funding to general practices. For some respondents, the experience of setting up the primary care network, establishing cross-practice working, and having to use new resources largely to deliver services required by NHS England and Improvement, had led to frustration and even talk of leaving the network. This was based on an assessment of the work entailed in running a primary care network and its shared services, and the burden experienced by practices 'losing' GP and management time to support the new organisation. Relationship with the wider NHS system The relationship between clinical commissioning groups and primary care networks varied - some clinical commissioning groups had supported networks development, providing resource and expertise to help establish inter-practice working, hire new staff, and operate contracts. Others had attempted to hold onto control delegated to primary care networks, closely monitoring budgets and spending decisions, and not operating within the spirit of national PCN policy. This evaluation took place during the first nine months of operation of primary care networks when they in their formative phase, learning how to work as a collective of practices, and forming relationships with their clinical commissioning group(s), local NHS trusts, and other partners. The experience of rural primary care networks We sought to study the experience of rural as well as urban primary care networks. Two of our case studies were in rural areas while another was semi-rural. Some of those in more rural areas felt that national PCN policy had been developed more with urban networks in mind, not accounting adequately for the experience of providing primary care in rural areas. A key aspect cited was that rural primary care has well-established ways of collaborating to meet local service needs, and patient populations who may be unwilling or unable to travel further to access new shared services. Conclusion We propose the following implications for local and national decision makers: 1) increasing engagement of GP practices and wider primary care teams with primary care networks; 2) building further leadership and management capacity; and 3) clarifying how primary care networks fit into the wider health and social care system, especially in the context of the Covid-19 pandemic and its aftermath. In further research, a mix of quantitative and qualitative measures will be needed to understand how networks contribute to improved sustainability, efficiency and integration in and beyond primary care. Studies will need to answer the question: do general practices need to collaborate to achieve these outcomes and if so, what policy, support and investment are required?",2020,2019,University of Birmingham,,Other,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,,2018 +C06189,NIHR131936,Local Authority Research Systems: developing Doncaster Council's road map to building greater organisational research capacity,"Research question: What mechanisms do we have to increase organisational capacity to undertake research? Background: This study is set in Doncaster Council the largest geographical metropolitan borough in the UK, with a population of around 305,000 people. Doncaster has an industrial past and this presents a significant challenge in connecting people, places and businesses to economic and social opportunities. Despite being relatively flat with many easily accessible green and blue spaces the borough has high levels of inactivity, low levels of participation in physical activity and high levels of deprivation. The 20/30 PHR call recognises that investment is needed to support the development of research capacity within local government. In Doncaster we have had opportunities to develop some capacity using local NIHR infrastructure. We are in a position to be lead organisation within this application. However, we are clear that much of this work has relied on relationships and the ability to spot opportunities. It has not, as yet, let to broader use of research findings within council decision-making. Moreover, although our research questions have arisen from practice the research has often been conducted in isolation and has not addressed policy or organisational research questions or needs. To date then we have not been able to bridge the gap between what is known and what is done. Our collective response to COVID19 brings these issues into sharp relief as there has been an increased urgency to access, use and understand evidence derived from research on the part of local government officers. There is an opportunity to do more as we learn to live in the time of COVID and an organisational recognition of the need to build better research capacity. In Doncaster we have pockets of research but not a research system; this then is the focus of our application. Aims: The study will address four aims: to identify what steps are needed to move from our existing ad hoc research projects to a research system designed to inform and support decision-making at Doncaster council; to establish what appetite is there amongst officers and elected members across the local authority to increase our organisational capacity to undertake research; to understand what types of people would be needed, in the local authority and elsewhere, to enable the authority to access research funding and successfully undertake high quality research and to identify what resources are needed to create a sustainable research system at Doncaster Council. Methods: The qualitative study will use individual interviews, observations and framework analysis techniques. A researcher embedded within the Doncaster Council will lead the data collection and analysis. Anticipated impact and dissemination: Outputs for the study will be those predefined by the funding call. Dissemination will benefit from a regional research infrastructure of academic and practice networks and include an actionable tool /guide for local authorities which will set out our learning and act as a signpost for others. Locally, this work will produce a vision for research, supported by a research capacity development framework, to inform decision-making and enable Doncaster Council to fulfil its ambition for the health and well-being of citizens.",2020,2020,Doncaster Council,56695.59,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research on Capacity Strengthening,Cross-cutting,2020 +C06190,NIHR131566,Public Health Intervention Responsive Studies Team (PHIRST): University of Newcastle,"Our team brings many years of experience in applied translational research in public health across three nations of the UK: Fuse Centre for Translational Research in Public Health in North East England; the School of Health and Related Research (ScHARR) at Sheffield; the Centre of Excellence for Public Health in Northern Ireland; the Scottish Collaboration for Public Health Research and Policy and the MRC/CSO Social & Public Health Sciences Unit. Hosted by Fuse, we build on its existing expertise from the innovative rapid response and evaluation service AskFuse service and UK wide links to other NIHR infrastructures and draw on experience with the national Public Health Practice Evaluation Scheme (PHPES), a response mode funded evaluation programme operated by SPHR. We are complementing both schemes by building capacity in responsive research with researchers and knowledge brokers across jurisdictions that enables a rapid response to the research and evidence needs of local government (LG). Our team combines expertise in local and national policy making from across the UK and, while members are located in the north of the UK, our networks cover the whole UK and we will draw on capacity within these networks. We understand the challenges LG faces in mobilising research evidence in a climate of austerity and within a political organisation that requires a range of different types of evidence and research designs to provide local policy makers and practitioners with knowledge that is timely, relevant and useful to ensure interventions work in their local context. The challenges facing LG will be made more acute by the current COVID-19 pandemic, the implications for which will be profound to LG and the communities they serve, particularly in terms of health inequalities. We value co-production as a core mechanism for creating meaningful relationships and knowledge to mobilise and implement evidence to address the most important research questions facing partner organisations. We have extensive experience of working with public health partners to co-produce research and translate high quality research findings into relevant, timely and useful outputs to inform decision-making in LG, build capacity and upskill staff. We will also draw on our experience and that of the LG partners to ensure meaningful public and community involvement in all aspects of our work, following the NIHR SPHR Public Involvement and Engagement strategy. Our model of approach follows a 5-step process: brokerage, work allocation, research, reporting & knowledge mobilisation (KM), and continuous improvement, which includes Evaluability Assessment methodology and embedded research with LG practitioners. With a track record in translational research, wide-ranging methodological expertise and with extensive networks with LG across the UK, we will be able to respond quickly and tailor research to local needs in collaboration with policy makers and stakeholders. Effective dissemination and KM is critical in ensuring impact. We will draw on our experience, applying the NIHR SPHR six knowledge sharing principles, in innovative ways to disseminate and mobilise our research findings into policy and practice, working with LG and the public, and tailoring outputs to relevant audiences, including Government, policy, practice and the public. We will maximise impact by collaborating with the other response teams to align projects and facilitate programme evaluation.",2020,2023,University of Newcastle,1925959.75,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C06191,NIHR131952,Local Authority Research Systems A qualitative study to inform the development of a South Gloucestershire Council wide research system,"Background: Public Health located within local authorities (LAs) enables leaders to take a population-level and non-clinical approach to meeting health needs and addressing and preventing issues using interventions and research. The co-location of expertise in public health, social care, and place services in LAs means problems influenced by the wider determinants of health can be tackled with transdisciplinary solutions. It also positions LAs as hotbeds for innovation, with successful models such as Oxfordshire County Council's Innovation Hub (iHub) enabling collaboration with academia and the private sector. There is a need for LA research systems to be formed that will enable LAs to become research active, lead and support the co-production of research with academia and the private sector, evaluate LA initiatives' impact on health and health inequalities, and the timely production and use of evidence to help shape practice and policy. Since 2014, the Public Health and Wellbeing Division based at South Gloucestershire Council (SGC) has developed an integrated academic function and is increasingly recognised for research. We recently conducted a qualitative study of the Division's staff, which found that while they valued and were interested in research and evaluation, they faced several barriers. These findings provide some insight into the conditions required to build an SGC research system and will supplement the information from the proposed project. Research Question: How do we create a research system in SGC to produce sustainable and influential research activity across public health, social care, and place services and who are the key stakeholders? Aim: We will conduct a mapping exercise and qualitative interviews to determine who are the key stakeholders in the research system and what is necessary for the system to sustainably produce influential and innovative research activity. Methods and Analysis: This project consists of two workstreams. The first is a mapping exercise that will identify key stakeholders within SGC and its local partners who are crucial to establishing a research system. We will include local NIHR infrastructure and organisations that are research active in the areas of public health, social care, and place. We will identify key roles, contact details, and research projects from each organisation from web pages, electronic reports, and personal communication. We will produce a briefing for each organisation to be compiled in a report. The second workstream is a qualitative study where we will conduct interviews with at least one key stakeholder from each organisation identified from the mapping exercise as well as SGC elected members and senior leadership. We will also interview the four Directors of Public Health who lead the West of England Public Health Partnership. Interviews will be semi-structured, one-to-one, last 30-45 minutes, and recorded. Interviews will be conducted using tailored topic guides and will explore several topics including relationships between SGC and local partners, key roles for developing a productive research system, resource and support, coproducing research, developing social care research, creating a joint innovation function, and the impact of COVID-19. Data will be transcribed, coded, and analysed using the framework method.",2020,2020,University of Bristol,56638.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research | Research on Capacity Strengthening",Community engagement | Health leadership and governance | Institutional level capacity strengthening,2020 +C06192,16/136/87,NIHR Global Health Research Unit on Improving Health in Slums at University of Warwick,"This unit will be led by the Warwick International Centre for Applied Health Research and Delivery (W-CAHRD), University of Warwick (UoW). Its staff and facilities will form the foundation of the proposed unit. W-CAHRD was set up in 2014 with core UoW investment, in line with the institution's strategic aim to increase international collaboration and support world-class global health research. Since inception, W-CAHRD has won 21 externally funded research projects worth £12.8 million and published 100+ peer reviewed global health papers, including a Lancet series on health in slums2,3. UoW provides core funding for a Global Research Priorities (GRP) programme to address the most challenging problems facing the world and to provide a platform for interdisciplinary research. W-CAHRD is represented on the programme and addresses 3 of the GRP's 11 themes: sustainable cities, health and international development. UoW will contribute matched funds and support unit sustainability (see justification of costs). Our unit will focus on how health services are delivered and used in slums, home to nearly a billion people, and identify options to improve affordable access for this group. Access to healthcare is a critical barrier to improved health in LMICs4. Universal Health Coverage (UHC) is a key element of the current global health agenda. It requires a set of physically accessible and financially affordable service providers, and a reduced burden of out-of-pocket expenditure5. All UN Member States have agreed to try to achieve UHC by 2030. Studying disease epidemiology is unhelpful if infrastructure is not in place to address it6. In the context of rapid urbanisation, poor economic growth, urban planning and regulation, slum populations are increasing. Slums, generally situated near to urban centres, are often physically closer to health services than rural settlements. Despite this, people in slums can have poorer health outcomes than their rural counterparts. This is due to the hazardous slum environment and poor access to appropriate healthcare2. In this vulnerable and marginalised group, child and maternal mortality remain high, as do infectious disease deaths, while non-communicable disease risk is growing2,7. Health emergencies are magnified in the slum environment. In the recent Ebola epidemic, the disease was concentrated in slums, and infected residents facilitated transmission throughout the city8. Poor people in LMICs are prone to catastrophic financial loss if they fall ill, and in slums, out of pocket expenses are essential to maintain life (e.g. to buy clean water)9. Observational studies of maternity care in Nairobi have documented a near absence of public facilities in slums. Private providers of varying quality fill the void8. Just 13.9% of people living in Dhaka's slums seek care from modern public providers, and coverage gaps exist10,11. Fragmented services may lead to poor co-ordination of care, reducing efficiency and resilience e.g. over-provision and/or under-provision of some services; reduced continuity of care; increased probability of developing drug resistance; reduced opportunities for disease surveillance. In slums, proximity to urban centres and population density mean that improvements to health service delivery could benefit many people simultaneously and have a large impact on health in LMICs. Our unit will seek to advance this issue. Objectives: Short-term To map geo-spatially current health service delivery arrangements and understand patterns of health service use (including equity of use) in slums in major and secondary cities. Medium-term To identify costs associated with different models of health service delivery arrangements in these slums, including by whom costs are incurred. Long-term To model options for health service delivery in slums, considering quality, cost-effectiveness and equity of provision. To develop capacity, communities of practice and a sustained research programme which exceeds the lifetime of the unit. Throughout To identify, synthesise and curate literature on potential models of health service delivery relevant to the slum context. To engage decision-makers and users in designing models of health service delivery in slums, with a view to subsequent evaluation of effectiveness and costs of viable options. To achieve the objectives work will be structured in 5 packages (WPs see Fig2,3). We have identified primary study sites, located in Kenya, Nigeria, Bangladesh and Pakistan (Fig1). These sites provide variety in social and physical factors, allowing us to examine diverse existing models of healthcare delivery. WP1: Geo-spatial mapping of health services in slums (Years 1-2). a)We will create accurate maps of the slums using participatory mapping instruments that combine local information to 'ground truth' data generated from Earth-observation satellite imagery. This methodology has worked in slums, with lay groups collecting data for the purposes of informing humanitarian aid organisations12. These maps have 2 functions: they will form the basis on which to overlay geo-spatial data on health service location (see b); they will inform our sampling frame in WP2. b)Local participatory mapping will be used to identify and add all health services present in the slum or available to people living in the slum to our maps, including hospitals, clinics, traditional healers, pharmacies etc. With our augmented map, we can calculate the area covered by mapped facilities and identify blind spots ; areas that are not covered or have a high distance/travel time to existing services. WP2: Household survey of health service use by slum residents (Years 1-2). A survey of health service use will be conducted with a stratified random sample of people living in the examined slums. Health service use will be investigated using questions adapted from a validated questionnaire (e.g.13). We will ask where healthcare has been sought by participants over the past year; for what health conditions; unmet healthcare needs; satisfaction with care received (a facet of 'quality'); and associated costs, including out-of-pocket costs. Data will be cross-referenced with WP1 to identify health services used by people living in the slums that are not recorded in the mapping, such as informal providers working from unmarked premises, services delivered at home (e.g. by community health workers) and those delivered outside the slums (e.g. secondary or tertiary care which is likely to be exclusively outside the slum area). Surveys will be georeferenced, so we can examine distance/travel time to health services. We will use Slum Dweller Association collected data14 to augment our findings. WP3: Curation and synthesis of the literature on models of health service delivery relevant to the slum context (Years 1-4). We will perform systematic reviews and overviews of the literature concerning relevant models of health service delivery with specific reference to delivery arrangements as defined in Lavis's taxonomy of structures and implementation strategies within health systems15. WP4: Simulation-based interactive design of optimal service models (Years 2-3). We will draw on insights from WP1-3 to develop simulation models representing alternative approaches to slum health service delivery. These will be used to evaluate affordability and efficiency of services as they currently operate, and provide a policy tool to predict the impact of adopting new approaches, or improving the organisation of existing ones, including estimates of resilience to seasonal or unexpected (e.g. conflict or epidemic related) demand surges. Models will take a broad economic perspective, populated by health service resource use data collected from providers identified in WP1, and patient/ household costs identified in WP2. We will estimate cost-effectiveness by modelling the impact of service configuration on health outcomes as far as possible given available data. The models will allow us to estimate the impact and value-for-money of existing and proposed service configurations, taking affordability and logistical constraints into account, in line with WHO Choosing Interventions that are Cost Effective (WHO-CHOICE) methodology16.The idea is to design optimal services according to resource and staff available and to provide a pathway of improvements, including the option of improving technical efficiency of existing models. WP5: Engaging stakeholders and implementing viable options for health service delivery in slums (Years 1-4). A series of workshops with stakeholders such as healthcare commissioners, providers and people who live in slums will be held in the cities studied. In year 1, workshops will seek to understand local policy-drivers, questions and concerns of local people relevant to the work and develop and prioritise research questions to be addressed by the unit. Year 4 workshops will examine viable models of health service delivery in slums informed by the evidence gathered in WP1-4. E.g. printed maps will facilitate discussion on the optimal location of future services; simulation models will provide a decision aid. WP5 will culminate with formulation of an action plan to implement favoured models of care with selected commissioners or providers of health services. Opportunities for pilot evaluation studies will be examined. While WPs are specified above, we have capacity to respond to emerging global health research requirements. Notably: WP3 is designed to be flexible to allow evidence synthesis activity to support our developing work programme; specific PhD projects will evolve in response to stakeholder priorities (including those of our academic partners) explicated in Year 1 workshops; in years 3-4 we have allocated flexible researcher time to exploit data collected and methodology developed, and to pursue promising leads arising during years 1-2.",2020,2021,University of Warwick,7392798.04,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Other,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Africa | Eastern Mediterranean | Europe | South-East Asia,,,,United Kingdom,Kenya | Nigeria | Bangladesh | Pakistan | United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery | Health financing,2017 +C06193,CV001,"Understanding infectivity, progression and disease severity of COVID-19 in children [Co-funders: CZI, Rosetree]",This study will analyse ACE2 and entry associated proteins (such as the viral S protein priming protease TMPRSS2) within the upper airway of children to test the following hypothesise: Hypothesis 1: Reduced expression of ACE2 (cell entry receptor hijacked by the coronavirus) and entry-associated proteins (such as the viral S protein priming protease TMPRSS2) within the upper airway of children compared to adult nasal epithelium is associated with reduced susceptibility and severity of COVID19. Hypothesis 2: Increased expression of immune-associated anti-viral genes in paediatric nasal epithelium compared to adult nasal epithelium accounts for the reduced susceptibility and severity of COVID 19.,2020,2020,Wellcome Sanger Institute,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease susceptibility | Disease pathogenesis",2020 +C06194,CV002,Single cell molecular signatures in blood and tissues from mild and severe COVID19 patients,"Key questions: What immune pathways and cellular phenotypic states distinguish COVID-19 severity? How do immune cell populations in blood and lung relate in severe COVID-19? Aims: To uncover immune signatures underlying severe disease, revealing candidate immune pathways involved in pathogenesis, Identify candidate predictive biomarkers for larger scale studies, Rapidly provide robust in vivo evidence to guide therapeutic intervention",2020,2020,Wellcome Sanger Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06195,CV004,Investigating longitudinal immune responses to SARSCoV-2 in young and old adults,"Our key research questions are: How does the tissue immune response to the virus differ between young and old? How does the tissue immune response to the virus differ between older individuals who get mild disease versus severe disease? In those with severe fatal disease, does the nature of tissue immune responses across organs?",2020,2020,Wellcome Sanger Institute,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06197,CV009,INSIGHT: Developing reagents for COVID-19 diagnosis and mutational analysis,Development of a two-stage testing assay for the COVID-19 pathogen. Fluorescent/dipstick-based viral RNA detection first stage (10-100 copies detected) and a centralised sequencing second stage to further improve the accuracy of the test. This two-stage testing strategy may be suitable as a home-based or point-of-care assay.,2020,2021,Wellcome Sanger Institute,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06198,CV015,Susceptibility of human fetal cells to SARS-CoV2 and viral infection,"In this study, we will assess the susceptibility of fetal cells and tissues, that are likely to encounter virus following vertical transmission, to SARS-CoV2 infection. Key questions: • Can fetal cells sense and respond to SARS-CoV2? • Can fetal cells become infected to SARS-CoV2? • What are the immunological and molecular consequences of sensing of and infection by SARSCoV2 to fetal cells and their tissue microenvironment?",2020,2021,Wellcome Sanger Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06199,1.01501E+13,RECoVERED,"As the rapid and unprecedented global spread of COVID-19 is disrupting society worldwide, there is an urgent need to address essential knowledge gaps for optimal clinical and public health management. Important gaps in clinical and pathophysiological knowledge can only be answered through close follow-up of individuals following SARS-CoV-2 infection at a range of disease severities. We will establish a cohort of 300 individuals suffering from different levels of disease severity, ranging from mild illness in community-dwelling individuals to life-threatening illness requiring hospitalization, and follow them at regular intervals for a maximum of 9 months. Using data and biological specimens from this cohort we will (1) identify clinical, virological and/or host factors/response markers predictive of disease progression, (2) determine the kinetics, persistence and protective capacity of SARS-CoV-2-specific antibodies during and following COVID-19 at different levels of disease severity, (3) evaluate characteristics of B and T cell subsets characteristics associated with development of potent neutralizing antibodies, and (4) assess mid- and long term sequelae of COVID-19 and their determinants with respect to morbidity and mortality, pulmonary function, quality of life and psycho-social wellbeing. In addition, a data- and biobank will be established for future, in-depth pathophysiological, immunological, host-genetic and further clinical and epidemiologic studies. Outcomes of this study will help to guide interventions to prevent spread and reduce the severity of illness.",2020,2021,Amsterdam University Medical Centre,696170.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C06200,1.01501E+13,ANAkinra for the treatment of CORonavirus infectious disease 2019 at the Intensive Care (ANACOR-IC),"ANACOR-IC focusses on critically ill COVID-19 patients treated with anakinra as part of their treatment regimen. Anakinra is an IL-1 blocker, central to the detrimental immune response that occurs in severely ill patients with COVID-19. For this study, patients randomized within the COVID-19 Immune Modulation domain of REMAP-CAP (to anakinra, no intervention, or other immune modulators) will be sampled, and immune profile, coagulation and -omics data will be combined with clinical data to produce a unique dataset. REMAP-CAP is an international Adaptive Platform Trial that investigates the best treatment for hospitalized patients with COVID-19. It was set up to include severely ill CAP patients and to adapt in case of a pandemic, as has now occurred in the SARS-CoV-2 pandemic. ANACOR-IC aims to provide detailed insight into the pathophysiological mechanisms and effectiveness of anakinra for this novel disease.",2020,2021,Utrecht University Medical Centre,753784,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C06201,1.01501E+13,COntrol of COVID-19 iN Hospitals (COCON-study),"This study will evaluate the sero-epidemiology in healthcare workers (HCWs) in Dutch hospitals in regions with varying incidence of COVID-19. Study design: Cross-sectional study with prospective follow-up during 3 months. Study population: 2000 HCWs employed in one of the participating hospitals. Main study endpoints: Primary endpoint: seroprevalence of SARS-CoV-2 neutralising antibodies. Secondary endpoints: seroprevalence of SARS-CoV-2 total antibodies, cumulative incidence of seroconversion for SARS-CoV-2 (neutralising) antibodies, sqRT- PCR-confirmed SARS-CoV-2 infection, virus culture-confirmed infection, self-reported symptoms suspected for COVID-19, (unplanned) absenteeism, hospital admission and death.",2020,2021,Utrecht University Medical Centre,690099.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +C06202,1.01501E+13,"Monitoring the evolution, spread and transmission of SARS-CoV-2 through whole genome sequencing to enable fast genotype to phenotype prediction","Emerging viral infections, once established in the human population, may evolve with continued circulation. The evolution of SARS-CoV-2 in the Netherlands will be monitored throughout the phases of the pandemic with close to real-time whole genome sequencing, allowing fast responses in case of remarkable genomic changes, and providing a reference database for investigation of community outbreaks. Bioinformatic tools will be developed to rapidly identify changes that may impact ability to detect, treat and prevent infections. In case novel lineages start to emerge, the effects on transmission dynamics will be further investigated using in vitro and in vivo studies to specifically look at the receptor binding properties, pathogenicity and other relevant virus properties. The results will directly inform precise public health decision making to control the outbreak.",2020,2021,Erasmus Medical Centre,483823.6,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C06203,1.01501E+13,Social Impact of Physical Distancing on Vulnerable Populations during COVID-19,"The aim of this mixed-method social science study is to document the challenges, experiences and creativity of socially vulnerable Dutch populations during social isolation. What kinds of problems do people run into? Do they find solutions to these problems? What (other) solutions can be generated? How can policy support these solutions? The main target groups are: 1) older adults, among those people living alone; people with dementia; people living in care- and nursing homes; 2) people with severe psychiatric problems; 3) people with learning disabilities; 4) homeless populations.; 5) families with young children, and 6) families deaing with issues of domestic violence (indirect through professionals). Our aim is to provide actionable lessons about measures that can be taken to sustain social distancing. The rationale for this is that, if we have better insight in what the challenges are for vulnerable people to endure social isolation, we can develop policy and communication strategies to remedy this. Hence, social isolation can be made more humane and easier to bear. Using existing networks, we will conduct digital ethnographic and survey research among professionals, family, and others caring for groups regarded as vulnerable. We will assess what problems people experience and document solutions people find. We will distill policy lessons learned in consultation with societal partners and provide recommendations.",2020,2021,University of Amsterdam,385907.2,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Policy research and interventions,2020 +C06204,1.01501E+13,Safety and efficacy of SARS-CoV-2 antibodies,"Treatment for COVID-19 is urgently needed but safety and efficacy of novel candidate therapeutics need to be assessed first before phase 1 clinical trials start. Therefore, appropriate in vitro and in vivo assays need to be included in a pre-clinical development workflow. These assays need to be carefully selected, optimized and streamlined in order to provide the appropriate data for rapid response and treatment development. The knowledge on COVID-19 intervention strategies and potential side effects of those is now accumulating, and a pre-clinical safety and efficacy assessment workflow needs to be able to easily and rapidly accommodate additional assays. One of the promising treatment options for COVID-19 includes the use of virus-neutralizing antibodies that block virus entry into the cell and thus are considered powerful means to block viral infection. However, several studies suggest that low level (non)-neutralizing antibodies may pose a risk for severe lung disease on virus re-exposure. The latter should be included in the safety assessment of candidate antibodies as early as possible in order to prioritize Abs that are not going to fail in the later stage of the (pre-) clinical development. The current proposed project aims at contributing to the rapid international public health response against SARS-CoV-2 by (i) testing the efficacy and safety of lead candidate SARS-CoV-2 neutralizing monoclonal antibodies (e.g. the antibody 49D11 and others identified by Erasmus MC and AMC) using in vitro assays and in vivo animal models; and by (ii) developing, validating and sharing with the research community a workflow of protocols for rapid testing of the efficacy and safety of recently identified candidate antiviral antibodies and plasma preparations for (a) efficacy and safety in in vitro systems; and (b) efficacy and safety in in vivo animal models. Altogether, we aim to bring a candidate Ab to a phase 1 clinical trial and to provide the research and development community with a streamlined workflow for the rapid efficacy and safety assessment of novel Ab-based therapeutics against COVID-19.",2020,2021,Erasmus Medical Centre,481382.18,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06205,MR/V028650/1,Understanding the impact of COVID-19 on the mental health of Peruvian older adults,"The COVID-19 pandemic has disproportionately affected older adult populations worldwide. Older adults have the highest morbidity and mortality due to COVID-19. Restrictive mobility measures (quarantine, and/or social distancing) aim to reduce viral transmission and protect the most vulnerable. However, there are likely to be unintended consequences of such restrictive measures on the mental (and physical) health of older adults, including increasing feelings of loneliness, reduced physical activity, depression and anxiety. Thus, studies that seek to understand the direct and indirect impacts of COVID-19 on the mental health of older adults are urgently needed, particularly among countries with less robust social and health systems such as Peru. Peru, a middle-income country, has experienced one of the highest rates of COVID-19 infection and deaths per million people. Furthermore, adults 65 years of age and over represent around 10% of the Peruvian population, and around 25% of them live in poverty. The overall objective of this research proposal is to understand the impact of the COVID-19 pandemic and consequent restriction measures on the mental health of older adults from low socioeconomic conditions in areas of Lima, Peru. We plan to conduct a qualitative study, remotely by telephone, using open-ended questions to elicit the points of view and experiences of older adults. Results from this study will generate data to inform future interventions and policy to mitigate the effects of restrictive mobility measures on the physical and mental health of older adults from this and other low resource settings as the pandemic progresses.",2020,2021,University College London,57469.24,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Peru,Peru,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C06206,MR/V033441/1,"COVID-19 Neurological Disease: a Global Meta-Analysis and Prospective Case Control Study in Brazil, India and Malawi","Building on our NIHR Global Health Research Group on Acute Brain Infections (""Brain Infections Global"" or, ""BIGlobal""), which we have recently repurposed to start understanding COVID-19 neurology, we will: 1. Conduct an individual patient data meta-analysis of patients with COVID-19associated neurological disease, identified through the BIGlobal COVID-Neuro Network to define the full spectrum of manifestations. 2. Establish a prospective case control study of hospitalised COVID-19 patients in Brazil, India and Malawi, comparing those with neurological disease to those patients without neurological disease, focusing on risk factors which may be modifiable. 3. Examine outcomes of hospitalised patients with COVID-19 associated neurological disease, looking for prognostic factors associated with a poor outcome. 4. Building on our strong Patient, Public and Community Engagement and Involvement Programme, and close relationship with WHO and national policymakers, use the information from 1, 2, and 3, above to develop national and international clinical care guidelines to improve patient outcomes and reduce disability. 5. Strengthen capacity for emerging brain infections research in partner countries. The case control study will test the primary hypothesis that among hospitalised patients with COVID-19, acute neurological disease is associated with hypoxia. The meta-analysis, case control study, and work with policymakers will run in parallel, to ensure rapid delivery of the changes needed to impact on practice. The study builds on 25 years of research on brain and emerging infections from the Liverpool group, much of which has been translated into new policy and practice.",2020,2022,University of Liverpool,584753.44,Human Populations | Other,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Americas | South-East Asia,,,,United Kingdom,Brazil | India | Malawi,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C06207,unknown,The DOMINO Study: measuring and mitigating the indirect effects of COVID-19 on tuberculosis and HIV care in Indonesia,"Indonesia has recently strengthened efforts to control HIV and tuberculosis (TB), but the diversion of resources to the current pandemic combined with social distancing policies is creating new vulnerabilities and exacerbating existing ones for people who rely on TB and HIV services. Indonesia urgently needs to understand the wider impact of the pandemic on TB and HIV care to inform mitigation strategies. This project will build on strong, existing collaborative research relationships to rapidly assess the impact of COVID-19, and policy responses to it, on the delivery of, and access to, TB and HIV care, with a particular emphasis on highly vulnerable populations. Findings will be used to design strategies to safeguard the continuity of care for TB and HIV patients in the near and medium term, thereby ensuring the country does not lose ground on the major advances it has made towards the control of these diseases. ""This project will provide directions to strengthen the tuberculosis and HIV program's resilience in Indonesia that has been challenged by the COVID-19 pandemic."" Professor Ari Probandari, Universitas Sebelas Maret and the Center of Tropical Medicine, Universitas Gadjah Mada, Indonesia",2020,-99,"London School of Hygiene & Tropical Medicine, Universitas Gadjah Mada, Sebelas Maret University, UNSW Sydney, Ministry of Health, University of Indonesia, United States Agency for International Development (Indonesia)",,Human Populations | Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe | Western Pacific,Western Pacific,,,,United Kingdom | Indonesia | Indonesia | Australia | Indonesia | Indonesia | Indonesia,Indonesia,Health Systems Research,Health service delivery | Health information systems, +C06208,unknown,Household transmission and immunity to SARS-CoV-2 among paediatric clients of a primary care centre in a low-resource community in Rio de Janeiro,"Understanding SARS-CoV-2 in children is important for their health, as well as for their families and communities, particularly in crowded living conditions such as slums, where households are very small and it is almost impossible to keep children within their homes.The aim of this project is to study the household transmission dynamics of the COVID-19 in a favela in Rio de Janeiro, Brazil. The researchers will examine and test for COVID-19 in a sample of children and their families from one of the poorest neighborhoods of the city, with regular follow-up visits over two years. The study expects to bring more evidence to the role of children in disease transmission, answering questions such as whether adults catch the virus at work, then transmit it to their children or do children catch the virus from neighbours, then bring it back to their families. ""The risk of catching SARS-CoV-2 comes down to a variety of factors, from genetics, to behaviour, to the environment in the home. We're hoping to tease variables apart with statistical models and figure out which ones are the most important."" Leonard Bastos, Associate Researcher, FIOCRUZ, Brazil",2020,-99,"Oswaldo Cruz Foundation, London School of Hygiene & Tropical Medicine, University of Exeter",,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Americas | Europe,Americas,,,,Brazil | United Kingdom | United Kingdom,Brazil,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C06209,unknown,"African critical care registry network for pandemic surveillance, clinical management and research (CRIT Care Africa)","Bringing together the expertise of researchers and clinicians based across low- and middle-income countries and partners from established critical care and pandemic networks internationally, this project aims to address the knowledge gaps that exist in the natural history and clinical course of COVID-19 related critical illness in Africa. Knowledge gaps and underlying operational gaps will be identified by implementing a setting-adapted registry for service evaluation and pandemic research in seven countries across Africa. Leveraging the registry data, and led by healthcare stakeholders, the researchers will identify priorities for improving processes of care for the sickest patients. Once established, the same registry platform will support trials to identify strategies for optimal supportive care and interventions in the management of critically ill patients. ""Without data we cannot engage in research, and without research we have no voice."" Prof Madiha Hashmi, co-investigator, Ziauddin University, Pakistan",2020,-99,"University of Oxford, African Coalition for Epidemic Research - Response and Training, Aga Khan University Nairobi, Debre Berhan University, Doctors with Africa CUAMM, D'Or Institute for Research and Education, Intermediate Hospital, International Forum for Acute Care Trialists (InFACT), International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), Mahidol Oxford Tropical Medicine Research Unit, Makerere University, Muhimbili University of Health and Allied Sciences, NICS-MORU, University of British Columbia, University College London, University of Edinburgh, World Health Organization, Ziauddin University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Africa | Americas | Eastern Mediterranean | Europe | International | South-East Asia | Western Pacific,Unspecified,,,,United Kingdom | International | Kenya | Ethiopia | Italy | Brazil | Namibia | International | United Kingdom | Thailand | Uganda | Australia | Tanzania | Sri Lanka | Canada | United Kingdom | United Kingdom | International | Pakistan,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management", +C06210,unknown,Promoting health and safety in traditional food markets to fight COVID-19 in Peru and Bolivia,"This project will design bespoke plans to reduce COVID-19 transmission in two markets in Sacaba, Bolivia, and two in Huancayo, Peru, and will support similar plans elsewhere through the development of a user-friendly tool that will be made available online. In collaboration with health services in these two localities, the researchers will pilot a health promotion plan for market sellers and their families that will include early detection and follow-up of COVID-19 infections. Data from the follow-up of a high-risk population will be valuable to answer questions in relation to COVID-19 infection. Enhanced local capacity resulting from the project will not only help facing the current pandemic but also future public health emergencies.",2020,-99,"Royal Veterinary College, London School of Hygiene & Tropical Medicine, Universidad Peruana Cayetano Heredia, National University of San Marcos, University of San Simón",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Americas | Europe,Americas,Digital Health,,,United Kingdom | United Kingdom | Peru | Peru | Bolivia,Peru | Bolivia,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C06211,MR/V028537/1,"Measuring unanticipated opportunity costs of South Africa's COVID-19 response for children, mothers and people living with non-communicable diseases","Before the COVID-19 epidemic, SA's life expectancy was on an upward trajectory, with gains towards 2030 SDG targets. In response to the epidemic, the government instituted a lockdown to flatten the curve. Though there have been benefits, there are questions about the impact on non-COVID-19 health outcomes. Rapid decision making has also left community perspectives behind. SAMRC Centre for Health Economics and Decision Science-PRICELESS SA & the MRC/Wits Agincourt Unit have partnered to investigate this. Our hypotheses are firstly, that during COVID-19 epidemic there has been and will continue to be a decrease in supply and demand of routine health services which may impact on morbidity and mortality for individuals with HT, Diabetes, pregnant mothers and children under 5. Secondly, the perspective of health workers and community members regarding provision and access to routine health services during the COVID-19 epidemic will differ from that of public policy makers. The proposal aims to quantitatively measure the impact of diverting a workforce who are managing COVID-19, on routine preventive and curative health services. This will include supply and demand side perspectives. We will also qualitatively evaluate the views of the public and of healthcare workers in rural and urban areas. This will be a mixed-method study with a multi-disciplinary approach that will quantify health service opportunity costs due to the COVID-19 response. We will use a time series analysis of health services headcount data, addressing geographical and equity impacts, and qualitative interviews to understand the perspective of the public and health workers. The results will enable policymakers to make evidence-based decisions regarding resource allocation, between maintaining health services and mitigating the epidemic, that are also responsive to community needs and priorities. Our robust track record of policy action research over a decade in SA predicts a successful outcome.",2020,2022,Wits Health Consortium (Pty) Ltd,436252.1,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women | Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C06212,unknown,"Spectrum, determinants and long term outcome of SARS-CoV2 infection and disease in African children.","Children in LMICs experience a very high burden of pneumonia, which continues to be the major single killer of children under five years of age. Risk factors such as malnutrition, pollution, crowded living conditions and the high burden of infectious diseases all contribute to the vulnerability of children to developing severe pneumonia in these settings. However, surprisingly children in LMICs and globally are only mildly affected by COVID-19, with very few severe cases or deaths occurring in young children. This project will investigate what factors protect children against developing infection or severe disease from COVID-19 across LMICs and whether prior infection with other organisms, including seasonal coronaviruses, protects children against severe disease through development of immunity. This project will provide new information on COVID-19 in childhood, protective factors, immune responses and the long term impact on child health. ""This funding provides a wonderful opportunity to better understand COVID-19 in African children in a low and middle income country context. Children are usually very vulnerable to developing severe pneumonia, however this hasn't occurred with COVID-19. Understanding why children are only mildly affected may be key to develop new strategies to prevent or ameliorate illness."" Professor Heather Zar, University of Cape Town, South Africa",2020,-99,"University of Cape Town (South Africa), University of Western Australia (Australia), University of Southampton (UK)",,Human Populations,Black,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C06213,MR/V029363/1,"The impact of COVID-19 on primary health care service provision and utilisation in Tanzania, Sierra Leone and the Democratic Republic of Congo","The impact and implications of the COVID-19 pandemic on routine primary health care provision and utilisation in resource-poor settings is unknown. Initial reports suggest that as health care workers with comorbidities or pre-existing conditions are taken off the 'frontline', others are transferred to COVID-19 response activities, fear of COVID exposure increases absenteeism, and social distancing measures are put in place in health facilities, the capacity to provide services has been reduced. Utilisation has also been affected, potentially by users' fear of catching SARS-CoV-2 infection at health care facilities, misconceptions that services are shut, barriers to accessing health care due to fewer transport options and less disposable income during lockdowns. A reduction in primary healthcare provision could be particularly devastating in low income settings. This multidisciplinary project aims to investigate the impact that the COVID-19 pandemic is having on primary healthcare providers and users in three distinct settings in Central (Democratic Republic of the Congo), East (Tanzania) and West (Sierra Leone) Africa, by building on existing collaborative partnerships. We will conduct the following activities: 1 Data will be collected from healthcare facilities to estimate the change in the number of people seen for essential services e.g. antenatal care, outpatients, routine immunisations, family planning and HIV comprehensive care visits. 2 Qualitative interviews will be conducted with primary healthcare workers to understand barriers and facilitators for effective care provision during the COVID-19 outbreak. 3 Healthcare workers' exposure to SARS-CoV-2 will be estimated in a repeated sero-survey, using a validated serological assay. 4 Qualitative interviews will be conducted with a selection of healthcare users to understand barriers and facilitators of utilisation. 5 A set of recommendations/ key findings will be formulated together with stakeholder",2020,2021,London School of Hygiene & Tropical Medicine,548805.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Congo (DRC) | Sierra Leone | Tanzania,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C06214,MR/V02860X/1,"SARS-CoV-2 infection, transmission dynamics and household impact in Malawi (SCATHIM)","Sub-Saharan African countries have adopted prevention measures similar to those used in developed countries to combat the SARS-CoV-2 virus (COVID-19) pandemic, although their social, cultural and economic contexts are markedly dissimilar. Limited empirical data exist on SARS-CoV-2 transmission dynamics and the feasibility of prevention measures in diverse African households, to guide the adaptation of the preventive measures. We aim to determine the transmission dynamics, determinants and socio-economic impact of SARS-CoV-2 infection in households located in urban medium-density, urban high-density and rural-high density locations in Malawi, Africa. Our specific objectives are to (1) measure the secondary attack rates of SARS-CoV-2 infection within households of symptomatic and asymptomatic index cases, (2) assess how SARS CoV-2 susceptibility and clinical outcomes among household contacts of index cases are influenced by socio-demographic, nutritional and anti-SARS CoV-2 immunological status; co-infections (HIV, TB, malaria) and their treatments, and household environment, (3) assess the acceptability, feasibility, adoption and effectiveness of personal protective equipment among household members of index cases, (4) describe lived experiences of caregivers of SARS-CoV-2 index cases, and (5) estimate the direct and indirect costs associated with SARS-CoV-2 prevention and care in households of index cases. Through this study, we will generate contextually-relevant empirical data for identifying high risk individuals; predicting the intensity of SARS-CoV-2 transmission and the impact of preventive measures; and designing appropriate social safety nets for households affected by SARS-CoV-2. Our research team's existing engagement with policy makers and local health department will facilitate knowledge translation and enhance their pandemic response capacity.",2020,2021,University of Malawi College of Medicine,449923.83,Human Populations,Black,Unspecified,Rural Population/Setting | Urban Population/Setting,Other,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Malawi,Malawi,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Policy research and interventions,2020 +C06215,MR/V033433/1,The impact of the COVID-19 pandemic on people with severe mental illness and on mental health service provision in South Asia (IMPASS),"The COVID-19 pandemic has adversely affected lives and challenged healthcare provision and people with severe mental illness such as schizophrenia and bipolar disorder are likely to be disproportionately affected. This project will look at the impact of the pandemic on people with severe mental illness and on mental health care provision in Bangladesh and Pakistan. The project will specifically look at how individuals with severe mental illness have received and responded to advice about preventing spread of COVID-19, their well-being, health risk behaviors, quality of life and access to healthcare as well as housing issues, food security, domestic violence, employment and income. Using this evidence, the researchers will then work to inform strategies to mitigate the impact of the pandemic on people with severe mental illness and healthcare services. ""IMPASS creates a platform for generating evidence and influencing policy for providing better health care of people with severe mental illness and improving their wellbeing during the pandemic and beyond."" Professor Rumana Huque, ARK Foundation, Bangladesh",2021,2023,"Rawalpindi Medical University, ARK Foundation, University of York, Keele University, London School of Economics and Political Science, University of Dundee, National Institute of Mental Health & Neuro Sciences, National Institute of Mental Health",214548.58,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Eastern Mediterranean | Europe | South-East Asia,Eastern Mediterranean | South-East Asia,,,,Pakistan | Bangladesh | United Kingdom | United Kingdom | United Kingdom | United Kingdom | India | Bangladesh,Pakistan | Bangladesh,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C06216,MR/V030817/1,Development and pilot testing of an m-health intervention to reduce COVID-19 associated psychosocial distress among Nigerian healthcare workers,"The advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) across the globe has brought severe disproportionate distress on individuals, communities, health resources, and nations. The distress is increasingly eroding the mental health and wellbeing of patients and caregivers in contexts with precariously fragile health resources. Nigeria with all health parameters below the WHO standard is no exception. COVID-19 related distress in Nigeria is rapidly jeopardising the mental health and wellbeing of health workers, especially doctors and nurses who spend relatively more time with patients. Doctors and nurses, hereafter referred to as healthcare workers (HWs), are brutally besieged by long working hours, psychological distress, fatigue, and occupational burnout. Also, the HWs' exposure to the virus is exponentially increasing while some of the control measures, like social distancing, imposed by the government are depleting their social capital and social connectedness, further undermining their mental health and wellbeing. However, m-health intervention is increasingly seen by some experts as a game-changer in the context of solutions to mental health and wellbeing challenges. Therefore, this project investigates COVID-19 associated psychosocial distress and evaluate the feasibility and pilot-testing of a guided m-health intervention among Nigeria's HWs. The study will use mixed-method to collect data for pilot-testing a guided m-health intervention to reduce Covid-19 associated psychosocial distress among the HWs in selected tertiary hospitals, Southwest Nigeria. The findings of this project would provide useful information on the feasibility of using such intervention for improving the psychosocial health of Nigerian HWs.",2020,2022,"Obafemi Awolowo University, Nigeria",105952.04,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C06251,881224,DECODE reDucing the health and Economic COst of Diagnostic uncErtainty: establishing potential applications of BV™ and its composite biomarkers in COVID-19 detection and patient management,"Problem: Clinicians routinely face diagnostic uncertainty because acute infections are often clinically indistinguishable and today's diagnostics have constraints. This uncertainty leads to inappropriate patient management, including antimicrobial misuse and avoidable hospitalization. The associated health economic burden are inferior patient outcomes, elevated costs, and antimicrobial resistance (AMR), one of the top 10 threats to global health. Potential solution: In many instances, the clinician only needs to know with confidence if the infection is bacterial or viral to decide how to manage a patient suspected to have an acute infection. We have developed and validated MeMed BV™ - a pioneering test for distinguishing between bacterial and viral infections that decodes the body's immune response to infection. BV™ has been both double-blind and externally validated in clinical studies enrolling thousands of patients and demonstrated superiority to biomarkers in routine use. Concurrently, we have developed Key™, an easy-to-use POC platform that runs BV™ in 15 minutes. To establish potential applications of BV™ and its composite biomarkers in managing COVID-19 patients, the following objectives are proposed: 1. To deploy BV™/Key™ at hospitals in Israel, Germany and Italy that are managing COVID-19 patients. 2. To collect real world evidence to support the performance of BV™ in identifying early viral infection and predicting/monitoring disease severity of COVID-19 disease. 3. To mature the BV™/Key™ system based on lessons learned during deployment. Impact: Fulfilment of Objectives 1 and 2 will pave the way to full EU commercialization of the BV™ biomarkers as an aid in COVD-19 patient management. Obtainment of Objective 3 will mature the BV™/Key™ system in readiness for a wider launch to support the fight against COVID-19. Taken together, the efforts of this project will take BV™ on Key™ from a regulatory cleared test to one that is available commercially and adopted in routine care and is ready for broader launch. By providing an actionable tool that reduces diagnostic uncertainty, this project will improve patient outcomes while reducing healthcare costs and help fight AMR.",2020,2021,MEMED DIAGNOSTICS LTD,2708370.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Eastern Mediterranean,Eastern Mediterranean,,,,Israel,Israel,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C06295,PISAC-COVID- 19-00021,The implementation of public policies to respond to the crisis unleashed by the COVID-19 pandemic: A look from the intergovernmental relations and networks of politics,,2020,-99,Instituto de Investigaciones Gino Germani [IIGG],82340.1,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C06296,PISAC-COVID- 19-00043,"State capacities in a post pandemic municipal agenda""",,2020,-99,Instituto de Investigaciones de la Facultad de Ciencia Politica y Relaciones Internacionales [II],82372.5,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C06297,PISAC-COVID- 19-00040,"Public support for household survival and economic units in emergency. Initiatives, mediations and scope of the assistance in a comparative perspective",,2020,-99,Instituto de Altos Estudios Sociales [IDAES],63000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C06299,PISAC-COVID- 19-00094,"Study on femicides in the context of covid-19 pandemic. risk factors, institutional responses and public policies compared in nine provinces of the Argentinian republic.",,2020,-99,Instituto Académico Pedagógico de Ciencias Sociales de la Universidad Nacional de Villa María [IAPCS],82062.47,Human Populations,Unspecified,Unspecified,Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Gender,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C06300,PISAC-COVID- 19-00117,Care strategies in contexts of urban and rural poverty in Argentina post-pandemic Covid-19,,2020,-99,Facultad de Ciencias Humanas [FCH],80025.59,Unspecified,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06301,PISAC-COVID- 19- 00022,"Nursing and health care professionals during the pandemic and post-pandemic COVID 19 (Argentina, century XX and XXI)",,2020,-99,UNQ-Universidad Nacional de Quilmes. Departamento de Ciencias Sociales [UNQ],82397.82,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Health Systems Research,Health workforce,2020 +C06302,PISAC-COVID- 19-00118,"Covid 19, health and social protection: contributions from territorial care practices for the strengthening of comprehensive SMC policies in the new post-pandemic scenarios",,2020,-99,Universidad Nacional de Lans [UNLA],81676.5,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C06303,PISAC-COVID- 19-00009,Effects of preventive social isolation on the exercise of the right to health in childhood Argentinian,,2020,-99,departamento de Humanidades [Departamento de],82481.25,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C06304,PISAC-COVID- 19-00014,Structural heterogeneity and inequalities persistent in Argentina 2020-2021: analysis dynamic of the reconfigurations caused by the COVID19 pandemic on policies national-provincial-local and their impact in the structure,,2020,-99,Instituto de Investigaciones en Humanidades y Ciencias Sociales [IdIHCS],82500,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health leadership and governance,2020 +C06305,PISAC-COVID- 19-00085,"Regional Research Program Comparative (PIRC): Recent changes in the Argentine social structure: work, income and social inequality in times of pandemic and post-pandemic",,2020,-99,Instituto de Investigaciones Gino Germani [IIGG],82462.5,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C06306,PISAC-COVID- 19-00023,The reconfiguration of inequalities linked to Argentine secondary education in pandemic / post-pandemic situation,,2020,-99,Núcleo de Estudios Educacionales y Sociales [Nees],82500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C06307,PISAC-COVID- 19-00029,Dynamics of Family Debt and Companies during the Pandemic and CODIV-19 post-pandemic. Impacts on Inequalities,,2020,-99,Instituto de Altos Estudios Sociales [IDAES],82500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C06308,PISAC-COVID- 19- 00051,"Identities, experiences and social discourses in conflict over the pandemic and post-pandemic: a multidimensional study about uncertainties, hatred, solidarity, unequal care and expectations in all the regions of Argentina",,2020,-99,Departamento de Ciencias Sociales [DCS],82500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience",Communication,2020 +C06309,PISAC-COVID- 19-00035,"Flows, borders and foci. The imagination geographic area in six urban peripheries of the Argentina during the pandemic and post-pandemic COVID19.",,2020,-99,Laboratorio de Estudios en Cultura y Sociedad [LECyS],62985,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C06310,PISAC-COVID- 19-00098,Discursive configurations in Argentina 2020. Emerging Narratives in daily life: an approach from feminist studies,,2020,-99,Facultad de ciencias Politicas y Sociales. Universidad Nacional de Cuyo FCPyS [FCPyS (UNCuyo)],63000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Gender,,,Argentina,Argentina,,,2020 +C06311,PISAC-COVID- 19-00081,"Radios and educational continuity in the context of social isolation: survey, diagnosis and guidelines to rethink the communication, education and connectivity in Argentina",,2020,-99,"Facultad de Periodismo y Comunicación Social- Instituto de Estudios Comunicacionales en Medios, Cultura y Poder ""Aníbal Ford"" [FP y CS INESCO]",56755.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C06326,2020/05338-3,Modulation of ACE2 in experimental hypertension and in response to treatment with ACE inhibitors and ARBs: potential implications on the severity and therapeutic targets of COVID-19,"Clinical evidence indicates that hypertensive patients are highly susceptible to infection and to the severity of COVID-19, a disease caused by the new SARS coronavirus SARS-Cov-2. SARS-Cov-2 requires activation of viral S protein by serineprotease TMPRSS2 and subsequent binding of active S protein to angiotensin-converting enzyme 2 (ECA2) to gain access to lung, heart and kidney cells, among others, in which ECA2 is expressed. ECA2, however, is a crucial enzyme component of the renin angiotensin system (SARS). ACE2 degrades angiotensin II (Ang II), a peptide with multiple actions that can lead to the development of arterial hypertension, and generates angiotensin-1-7 (Ang-1-7), which antagonizes the effects of Ang II. Besides that, experimental and clinical studies suggest that blockade of SARS by ACE inhibitors (ACE inhibitors) and type 1 angiotensin II (ARB) antagonists may increase the abundance of ACE2. Due to the fact that patients with arterial hypertension, among other cardiovascular diseases, are routinely treated with SARS blockers, a number of clinical concerns have arisen regarding the potential increased risk of these patients being infected with SARS-Cov-2. Notably, there are no studies in experimental or human models that have examined the effects of ACEI and ARB on protein abundance and ECA2 activity in the lungs, a possible route of infection. In addition, the effects of ACEI and BRA on the modulation of the serine protease TMPRSS2 in arterial hypertension are totally unknown. Furthermore, there is no information available in the literature to show that hypertension per se or male gender, factors that contribute to the poor prognosis of patients with COVID-19, modulate TMPRSS2. The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU) The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU) The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU)",2020,2022,Universidade de São Paulo,14379.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Gender,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C06327,2020/05416-4,Experimental strategies for investigating COVID-19-induced anosmia: is there a neurodegenerative component involved?,"The pandemic caused by the COVID-19 virus has led to the saturation of health systems around the world due to the severity of some of its respiratory symptoms. However, the report of patients about the onset of anosmia (decreased or loss of olfactory sense) with the course of the pathology, leads to the hypothesis of the participation of a neural and, perhaps neurodegenerative component of SARS-COV-2. In addition to a common symptom in respiratory viral infections, anosmia is also an early clinical sign of neuroegenerative diseases, such as Alzheimer's, Multiple Sclerosis and Parkinson's. The neural pathway that leaves the olfactory epithelium and reaches the olfactory bulb in the central nervous system is a neurogenic niche with regenerative capacity maintained in adulthood. Besides that, this pathway has an important cognitive and emotional role due to its connections with limbic areas such as piriform, entohrinal and tonsil cortex. The present work aims to study, using in vitro and in vivo strategies, the neural invasive mechanisms of COVID-19 in the sensory olfactory system, in addition to characterizing possible therapeutic targets and behavioral consequences associated with infection.",2020,2022,Universidade de São Paulo,32586.79,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C06328,2020/05430-7,"Multicenter, prospective, randomized, double-blind, placebo-controlled study to evaluate the effect of diacerein to prevent death or multiple organ dysfunction in patients with ARDS secondary to COVID-19","Since its report by the World Health Organization in February 2020, SARS-CoV-2 has spread rapidly at an alarming rate, becoming a pandemic on March 12, 2020. In early April, more than 1 million cases were reported. confirmed and there are no signs of slowdown in transmission. Brazil, with more than 10,000 cases as of the beginning of April 2020, is the most affected country in Latin America and its daily growth of confirmed cases is on an equal footing with the rest of the world. Pyroptosis is an inflammatory form of programmed cell death that occurs most frequently after infection by intracellular pathogens and has been described as occurring in severe coronavirus infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2. Through a direct effect of viral capsule proteins like viroporin 3a, the NLRP3 inflammasome is activated generating damage and rupture of the cell membrane. This process is further intensified with the activation of caspase-1 and production of gasdermine D and interleukin 1B (IL1B). In addition, cell death results in the release of DAMPs in neighboring cells and subsequent activation of the NLRP3 inflammasome, thus propagating the extent of the damage. In this context, reaching the inflammatory cascade and pyroptosis is potentially a viable way to control host injury in cases of severe COVID-19. Diacerein and its active metabolite, the reign, decreases the production of IL-1B AND cell death from pyroptosis by inhibiting caspase-1 E can also inhibit IL-6 production. The attenuation of the production of these inflammatory cytokines has the potential to decrease the severity of the disease, especially in those who are hospitalized with COVID-19. In cell models, the inflammatory response to IL-1B is completely reversed with diacerein treatment. In a rat model of acute sepsis-induced inflammation, diacerein reduced caspase activity and nuclear factor kappa B. Currently, there are no studies on the effect of diacerein on the acute inflammatory response in humans. However, when extrapolating human model data andin vitroin animals for patients with severe manifestations of COVID-19, it can be postulated that the attenuation of pyroptosis and inflammatory activation may be a clinical benefit for these patients. Diacerein has been on the market for approximately 20 years and has been approved for use in osteoarthritis and other inflammatory conditions such as Epidermolysis Bullosa. It is accessible and well tolerated by patients with rare cases of gastrointestinal disorder. For this, 300 patients will be enrolled in a double-blind, randomized, placebo-controlled study in which diacerein treatment will be tested. The primary outcome will be time to clinical worsening, defined as the time from randomization to mortality or worsening of the World Health Organization (WHO) progression scale.",2020,2022,Universidade de São Paulo,71556.94,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C06329,2020/04653-2,Molecular design and synthesis of inhibitors of the main protease of the coronavirus SARS-CoV-2 Mpro,"The current worldwide outbreak of the coronavirus with a pandemic declared by the World Health Organization (WHO) is beginning to strike in Brazilian lands. This pandemic urged us to start an emergency project in the search for new proteases inhibitors of the main coronavirus protease (SARS Cov-2 Mpro) as antiviral agents acting on the coronavirus. Several cysteine ​​protease inhibitors (CPs) under development in our group have 60-70% similarity in the coronavirus SARS 3C protease (CHEMBL3927), directly in the SARS coronavirus (CHEMBL612575) and also in feline coronavirus (CHEMBL612744). Mostly, our inhibitors are similar to the new SARS Cov-2 Mpro inhibitors. That way, we will initially test the entire NEQUIMED / IQSC / USP database in phenotypic assays to be carried out at the Institute of Biomedical Sciences, ICB / USP. Concomitantly, we will modify the structures of our PC inhibitors to improve the percentage of similarity to the best known inhibitors and for which we will seek evidence of action on the coronavirus disseminated in Brazil. In addition, we will immediately employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical stages. (AU) we will modify the structures of our CP inhibitors to improve the percentage of similarity to the best known inhibitors and for which we will seek evidence of action on the coronavirus disseminated in Brazil. In addition, we will immediately employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical stages. (AU) we will modify the structures of our CP inhibitors to improve the percentage of similarity to the best known inhibitors and for which we will seek evidence of action on the coronavirus disseminated in Brazil. In addition, we will immediately employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical stages. (AU) employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical stages. (AU) employ our artificial intelligence tools with machine learning to select test candidates from the drugs currently in therapy, experimental and investigational drugs and those drug candidates that are in clinical stages. (AU)",2020,2022,Universidade de São Paulo,70743.31,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C06330,2020/04680-0,Design of different fragments of the SARS-CoV-2 spike surface protein for the development of rapid and vaccine tests,"Our research group, in collaboration with researcher Dr. Edison Durigon of ICB USP, is developing a rapid test to detect COVID-19. For this, we have already managed to clone and express 4 fragments of the SARS-CoV-2 surface protein and have shown to be immonogenic against the serum of a human patient. For the production of the rapid test, proteins were produced on a large scale to inoculate in three animals (rat, rabbit and goat). We started inoculating three proteins in rats, goats and rabbits. The forecast is that in 21 days we will have enough serum to produce the first rapid tests. Due to the demand and urgency in the production of these fragments of the spike, I am coordinating a task force that also involves Prof. Shaker Chuck Farah to produce the 4 spike fragments in large quantities both to continue inoculation in animals and to do other tests. We have also ordered the synthesis of new oligos to build 4 more fragments of the virus's spike protein to try to obtain soluble proteins for vaccine development, this part of the project will be done in collaboration with Prof. Durigon and with Profa. Ana Marcia also from ICB USP. (AU)",2020,2022,Universidade de São Paulo,32609.7,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C06331,2020/04746-0,Understanding the molecular basis and the role of risk factors in Coronavirus infection (SARS-CoV-2 or COVID-19) in preclinical models,"Rapidly, SARS-CoV-2 viral infections took on pandemic dimensions, leading several countries to a state of public calamity. Using a methodology not directed by hypothesis, based on proteomic and metabolomic analyzes, the present project aims to identify the molecular mechanisms involved in SARS-CoV-2 infection in macrophage cultures, pulmonary epithelium as well as neurons and astrocytes. We will also investigate tissues from preclinical models such as brain, lung and bronchoalveolar lavage. We intend to provide clarifications about SARS-CoV-2 infection, proposing new therapeutic targets that can bring better perspectives regarding the spread of the disease and, consequently, provide an improvement in the quality of life of infected individuals.",2020,2022,Universidade Estadual de Campinas,32119.5,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06332,2020/04909-7,Using simulation to implement the COVID-19 suspect patient care protocol,"Clinical simulation plays a key role in updating and training new protocols. With the rapid growth of the contagion of COVID-19, it is extremely important to train health professionals who will care for patients allegedly contaminated with COVID-19. Thus, a simulated training was created that aims to implement the new protocol for the care of patients with suspected COVID-19 for all health professionals who work at the Hospital das Clínicas at Unicamp. Despite the importance of training, it is necessary to investigate whether it is being effective in acquiring knowledge, skills and the perception of feeling capable in the face of service, relationships with colleagues, autonomy and competence. Objective: This study aims to investigate the effectiveness of simulated training for COVID-19 in the acquisition of knowledge, skills and the feeling of feeling capable in the face of care, relationships with colleagues, autonomy and competence of the health professional. Method: this observational field study will include health professionals from Unicamp Hospital das Clínicas who agree to participate in the research. Health professionals will answer two questionnaires before and after training. The first questionnaire will contain 20 knowledge questions about the COVID-19 protocol. The second questionnaire will contain 14 questions regarding self-efficacy, that is, how much the professional feels capable of doing an activity, autonomy, relationship with the team and competence.",2020,2022,Universidade Estadual de Campinas,76574.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Health Systems Research,Health workforce,2020 +C06333,2020/04964-8,Activation of inflammasome by SARS-CoV-2 and the role of this platform in the pathogenesis of COVID-19: a prospective study aimed at inhibiting NLRP3 for the treatment of COVID-19,"COVID-19, caused by the new coronavirus (SARS-CoV-2) has become a worldwide health problem, with more than one million confirmed cases and 50,000 deaths by the beginning of April 2020. In its most severe forms, COVID-19 manifests itself in the form of fever, cough, fatigue, dyspnoea, headache and may progress to respiratory distress syndrome and death. The most severe cases are characterized by an intense inflammatory process, with important recruitment of classically activated neutrophils and macrophages. There are also high concentrations of inflammatory cytokines, such as IL-6 and IL-1², which is produced in a manner dependent on the inflammasome, a complex of intracellular proteins that promotes inflammatory processes. The presence of high concentrations of IL-1² in patients suggests an important participation of the inflammasome in the pathogenesis of COVID-19. Thus, we intend to evaluate the inflammasome activation in response to SARS-CoV-2 infection in cell cultures and in clinical material obtained from patients with COVID-19. We also intend to monitor inflammasoma activation in a prospective study with 60 patients hospitalized for SARS-CoV-2 at HC-FMRP who will be treated with chloroquine in combination (or not) with colchicine, a drug widely used for the treatment of mediated diseases by NLRP3 inflammasome, as a gout. Colchicine prevents the formation of tubulin dimers, inhibiting several cellular processes, including the activation of the inflammasoma. Thus, the development of this research project should directly contribute to the understanding of the pathophysiology of COVID-19, in addition to providing a mechanistic basis for the use of colchicine as a possible treatment for patients with COVID-19.",2020,2022,Universidade de São Paulo,65976.93,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis,2020 +C06334,2020/05761-3,Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories,"The persistence of human pandemics, emerging and re-emerging viruses and the evolution of viral strains dictate the search for new compounds with antiviral potential. Pandemics like the current one, caused by SARS-Cov-2, directly affect the sectors of health, economy, commerce, tourism and others. In addition, due to its high and rapid spread, there is a saturation of hospitals and health centers, a fact that contributes to the increase in deaths worldwide. In view of the current pandemic situation and the major global public health problem that the SARS-CoV-2 virus represents, in addition to the need to develop effective treatments for this disease and possible future epidemics / pandemics, the study aimed at the identification of new compounds with antiviral action against SARS-CoV-2. Thus, the aim of this study will be to identify and investigate the potential of peptides in virucidal, protective and inhibiting cytoplasmic viral replication activities. Peptides and bioconjugates have shown promising results at different stages of viral infection. At the end of the tests, the compounds will be classified into three groups (virucides, protectors and inhibitors of cytoplasmic replication) and we will identify the possible mechanisms involved in the regulation of SARS-CoV-2 replication. Additionally, we will evaluate the selected peptides together with commercial non-steroidal anti-inflammatory drugs in order to evaluate a joint treatment for the infection and for a possible inflammatory response, common in cases of infection caused by SARS-CoV-2.",2020,2020,Universidade Estadual Paulista (Unesp),70467.29,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C06335,2020/05230-8,Confronting Covid-19: Brazil in a comparative perspective,"The epidemic for the new coronavirus (COVID-19) has caused loss of life and illnesses for thousands of people, as health services and systems around the world have been tested. How have governments responded to the new coronavirus epidemic? What is the response time between the first cases and the actions to face the epidemic? Perhaps more importantly: how and why were these measures adopted? And what can be done to prevent a similar disaster in the future? In collaboration with the School of Public Health at the University of Michigan, our team integrates a study that seeks to identify the explanatory variables on the responses of different countries to COVID-19. This Fapesp financing will enable field research in Brazil in three ways: (i) to explore the response of the health system and policy throughout the development of the epidemic; (ii) investigate the social protection initiatives that have been adopted in order to make public health actions viable; (iii) analyze, compared perspective, how and why these decisions were adopted and propose recommendations. Qualitative methodology combined with analysis of epidemiological data will be used to explore the extent to which the following elements contribute (or not) to understanding the country's decisions: history of coping with public health emergencies; state capacity and crisis management in public health; coordination and initiatives by political parties. Our study will be one of the first initiatives and set of Brazilian publications to explore in depth, explanatory elements, guided by a comparative effort and international cooperation in the area. In addition, our publications will inform future studies on COVID-19 and help define the debates about what this epidemic means for the disciplines of comparative public policy and health policy management.",2020,2022,Escola de Administração de Empresas de São Paulo - FGV,51404.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health leadership and governance,2020 +C06336,2020/05985-9,Evaluation of the mechanisms of hemostasis activation in COVID-19 and its modulation by bradykinin inhibitors,"Serious forms of COVID-19 are characterized by intense activation of inflammation associated with a significant increase in the levels of hemostasis activation markers. According to the theoretical model of immunothrombosis, hemostasis and inflammation are inseparable elements of the innate response to pathogens. According to this model, when regulated, the activation of hemostasis contributes to the eradication of pathogens; but when deregulated, it can lead to secondary damage, such as the formation of thrombi in the microcirculation. It is interesting to highlight that the activation of hemostasis during inflammation occurs by means different from those activated in response to the loss of continuity of the endothelial line observed in post-traumatic bleeding, and involves elements such as the expression of tissue factor in monocytes and microparticles, the activation of intrinsic via DNA released from extracellular neutrophil networks, among others. In addition, breaking the endothelial barrier, which also contributes to the host's response to injury by mediating diapedesis, can be a secondary mechanism of injury, contributing to changes in the alveolar-capillary barrier or even to the activation of hemostasis. In this project, we will evaluate a panel of parameters linked to the activation of hemostasis and the regulation of the integrity of the endothelial barrier in patients with COVID-19 included in a clinical study that will evaluate the effect of bradykinin inhibitors on the clinical course of this disease. The panel will be evaluated at different times in the course of the disease (admission, days +4, +12 and +28), and the allocation by groups will allow conclusions about the evolution of the disease in patients on supportive treatment, or under use of bradykinin, which have the potential to modulate both the regulation of the integrity of the endothelial barrier, and the crosstalk between inflammation and the intrinsic coagulation pathway.",2020,2020,Universidade Estadual de Campinas,32652.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Clinical trial (unspecified trial phase),2020 +C06337,2020/04884-4,Study of the prevalence of Coronavirus COVID-19 in the blood donor population and evaluation of seropositive individuals for the production of hyperimmune serum,"COVID-19 is an acute respiratory disease caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2). In Brazil, it is a cause for concern due to its impact on health structures and the description of current mortality rates (especially in age groups above 60 years). Exponential growth of cases is expected and the assessment of their frequency rates such as morbidity, mortality, lethality, percentage of carriers and seroprevalence in the healthy population is essential to establish policies for action and surveillance. Objectives: 1. To evaluate the seroprevalence of the Coronavirus COVID-19 in blood donors at the Fundação Pró-Sangue Hemocentro de São Paulo. 2. Assess the feasibility of producing hyperimmune serum with individuals who have had their infection confirmed by PCR and from HIV-positive donors in screening the blood bank. 3. Develop an in-house IgG / IgM test that allows the expansion of epidemiological studies. Methods: Cross-sectional, prospective study in which an Elisa IgG antibody test for COVID-19 will be performed on 10,000 serum or plasma samples from FPS-HSP donors, from April to December 2020. Standardization of tests search for IgG antibodies and anti-SARS-CoV2 IgG1 and IgG3 subclasses. Quantitative real-time PCR test, ""in house"", which amplifies part of the RNA-dependent RNA polymerase RNA polymerase and COVID-19 envelope gene. Currently, in Brazil, screening for SARS-CoV-2 infection is performed by testing the oral / nasal mucosa using the polymerase chain reaction (PCR) method only in symptomatic patients, who are included in the definition of suspicious cases offered by the Ministry of Health. Health (MS). The search for IgG antibodies can be used as a marker to understand the epidemiology of SARS-CoV-2 infection and assist in determining the level of humoral immune response in patients. Although infections from immunocompetent patients usually show only mild symptoms, the elderly, pregnant women and patients with pre-existing diseases, develop more serious illnesses. To date, there is no specific therapy for the treatment of COVID-19 infection. Passive immunotherapy with convalescent plasma, which was already used in the epidemic in China by MERS and has been proposed for the treatment of COVID-19 infection, may be an alternative treatment in these cases.",2020,2022,Universidade de São Paulo,34960,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Disease susceptibility | Disease pathogenesis,2020 +C06338,2020/05369-6,Accelerated artificial intelligence strategy for drug repositioning against COVID-19,"The arrival of COVID-19 in Brazil in March 2020, with its rapid spread, exponential growth of cases worldwide and the high lethality of infected patients, has generated panic in the population, disrupted public and private health systems and impacted negative way in the economy of Brazil and the world. Although the search for an effective vaccine is the first arrival of COVID-19 in Brazil in March 2020, with its rapid spread, exponential growth of cases worldwide and the high lethality of infected patients, it has generated panic in the population, disrupted systems public and private health and negatively impacted the economy of Brazil and the world. Although the search for an effective vaccine is urgent, its development should take at least a year and a half before approval. Thus, the need to discover a treatment that can be quickly approved for use in infected patients becomes evident. Drug repositioning offers a potentially faster approach to identifying drugs already approved for use in humans. Artificial intelligence (AI) is a frontier area of ​​knowledge that allows the identification of potentially active compounds with appropriate pharmacokinetic and toxicological properties, leading to greater speed, greater success rate and lower cost in the discovery of new drugs. In this context, in order to transform drug discovery from a slow, sequential and high-risk process to a fast, integrated model with reduced risk of failure, this project aims to develop an integrated platform based on artificial intelligence for accelerate the repositioning of drugs already approved for use in humans for the treatment of COVID-19 with the potential for rapid clinical development, through the integration of high performance computing with chemical and biological data and the use of emerging biotechnological and experimental technologies. development should require at least a year and a half before approval. Thus, the need to discover a treatment that can be quickly approved for use in infected patients becomes evident. For this, we add different expertise from researchers at the Biology Institute of UNICAMP and other research institutions in Brazil and abroad and we will use a multidisciplinary approach that will involve the development and application of artificial intelligence tools to guide and accelerate the repositioning of drugs in use based on inhibiting virus entry into the host cell by inhibiting the interaction between viral Spike proteins and human ACE-2 and testing antiviral activity in cell culture in a level 3 biological containment laboratory. As preliminary data, in a accepted for publication, researchers involved in this proposal developed computational models and performed a virtual screening based on docking of all drugs approved by the FDA (~ 2,400 drugs) in viral glycoprotein spike complexed with human protein ACE2, with the grid centered on the interface of the two proteins. After docking, drugs were reordered using machine learning models developed using the Bayesian algorithm and ECFP6 fingerprint descriptors for SARS-CoV phenotypic data. At the end of this approach, 25 approved drugs were selected and will be subjected to in vitro tests against SARS-CoV-2 in Vero cells.",2020,2022,Universidade Estadual de Campinas,32846.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2020 +C06339,2020/05601-6,Neutrophil Extracellular Traps (NETs): importance in pathogenesis and potential therapeutic target in COVID-19,"2019 coronavirus disease (Covid19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has become a major health problem worldwide. The pulmonary changes observed in patients with Covid-19 are characterized by intense damage to epithelial and endothelial cells, viral replication in lung tissue and extensive inflammatory process characterized by edema, infiltration of inflammatory cells, including neutrophils and increased tissue concentrations of inflammatory cytokines , such as TNF- ±, IL-1 and IL-6. In addition to pulmonary changes, there is also a systemic inflammatory response with important lesions in other organs such as kidneys, heart and intestines. Recent studies suggest that neutrophils participate in lung injuries and possibly in other organs, but it is not yet clear what mechanisms are involved. Among the cytotoxic mediators released by this cell type are free radicals, enzymes and NETs (from Neutrophil Extracellular Traps) or, simply, extracellular traps of neutrophils, which are networks of DNA conjugated with antimicrobial enzymes such as myeloperoxidase (MPO), elastase and citrullinated histones. NETs are described as one of the main mediators responsible for injuries seen in several autoimmune diseases and also in vital organs during sepsis. However, the involvement of NETs in the injuries observed at Covid-19 remains unknown. Therefore, the objective of the present project is to identify the participation of NETs in the pathogenesis of Covid-19. The possible involvement of NETs in the pathogenesis of Covid-19 will allow us to propose new therapeutic approaches for this disease, that is, drugs that degrade this mediator and / or inhibit its synthesis. In this sense, we are also proposing to conduct an open clinical trial treating patients with Covid-19 with Pulmozyme. Pulmozyme is used in the clinic to treat cystic fibrosis and its active ingredient is DNAs that degrade NETs. Confirming the feasibility of the project, in a preliminary experiment, we observed an exacerbated production of NETs by isolated neutrophils and in the plasma of patients affected with Covid-19.",2020,2022,Universidade de São Paulo,70925.21,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06340,2020/05346-6,Interaction studies between cellular proteins and viral proteins of the new coronavirus 2019 (SARS-CoV-2),"SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), as well as SARS-CoV from 2003 and MERS-CoV from 2012, is part of the genus Betacoronavirus of the order Nidovirales and is currently the virus causing the pandemic called COVID- 19 (Coronavirus disease 2019). SARS-CoV-2 causes a severe acute respiratory syndrome or SARS, characterized by fever, cough, fatigue and severe cases of pneumonia, having affected more than 1.8 million people worldwide so far. Three of the virus's structural proteins, proteins E, M and N, are responsible for assembling the viral particle, among other processes. Protein N has a high affinity for viral RNA, forming the viral nucleocapsid. The membrane proteins E and M are responsible for the morphology of the virion and for interactions both with the protein S, which recognizes the cellular receptor, and with the viral nucleocapsid. The replication process of coronaviruses is highly regulated, involving different actions of the non-structural and structural proteins of the virus. However, little is known about which cellular proteins are involved in the assembly of the viral particles of the coronaviruses. This project aims to identify the interactome of SARS-CoV-2 E, M and N proteins in human cells, understanding their molecular interactions with cellular proteins and the cellular pathways that this virus benefits to complete its replication cycle. For that, we will do the optimization of the genes that encode E, M and N for expression in human cells, followed by immunoprecipitation and characterization by mass spectrometry of interacting cellular proteins. Once validated, such interactions will be challenged with pharmacological interventions in vitro, in order to verify their potential to block or interfere with viral replication. These compounds will finally be tested in an in vitro culture model of human cells infected with SARS-CoV-2, analyzing viral load, cytopathic effect and molecular changes in the cells. The present research project aims, therefore, to contribute to a better understanding of the molecular and cellular mechanisms associated with the replication of SARS-CoV-2 in human cells and to the rationalization of potential future therapies against COVID-19. (AU)",2020,2020,Universidade Estadual de Campinas,59657.85,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C06341,2020/04923-0,Glycosylation of SARS-CoV-2 to identify the structural characteristics of COVID-19,"SARS-CoV-2 is a human virus emerging from the Coronaviridae family. SARS-CoV-2 is the etiologic agent of a new pneumonia called COVID-19, coronavirus disease 2019. Due to the rapid increase in the number of cases affecting several countries, WHO has classified the outbreak of COVID-19 as a pandemic ongoing. As of April 1, there were 750,890 confirmed cases and 36,405 deaths worldwide. Understanding the virus-host dynamics is fundamental for the development of prophylactic, diagnostic and therapeutic strategies, in addition to the establishment of measures for the epidemiological control of COVID-19. Many molecular aspects still need to be understood about the behavior of SARS-CoV-2 and the host's response during infection, e.g. molecular and cellular markers of serious, mild and asymptomatic infections, providing a better understanding of the pathogenesis of COVID-19. In this project, we propose the application of a spatial and temporal proteomic approach to characterize the SARS-CoV-2: host interaction, to be addressed on three interconnected fronts: (1) evaluation of the signaling pathways activated by systematic quantitative analysis of the temporal dynamics in protein and glycosylation changes during infection of human cells by SARS-CoV-2; (2) characterization of the diversity of SARS-CoV-2 proteome and PTMs; and (3) development of an early diagnosis and prognosis platform based on the proteomic profile of sera from patients with different clinical characteristics. The proposed project will contribute to broaden the understanding of viral pathogenesis and will prioritize the discovery of biomarkers for rapid diagnostic tests.",2020,2022,Universidade de São Paulo,56541.32,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C06342,2020/04602-9,Development of antivirals for the treatment of COVID-19,"The rapid spread of the COVID-19 pandemic with exponential growth in cases in Brazil and worldwide, there is great concern about the lethality in those infected and the saturation of hospital beds to treat severe cases. Although the search for an effective vaccine is urgent, any development should require one to two years to be approved, so there is no expectation that it can be used even during this global pandemic. In this context, in addition to the necessary mitigating health measures, there is an urgent need for research on drugs with antiviral activity against the SAR-Cov-2 coronavirus, which can assist in the treatment of infected patients. In this project, a primary compound screening assay will be established and standardized, in an HCS (High Content Screening) model, using humans and the SARS-Cov-2 coronavirus isolated from Brazilian patients and grown under conditions of high biological safety (P3) at ICB- USP The forecast is that in this test it will be possible to evaluate up to 4,000 compounds, being able to expand this study according to the availability of compounds and resources for the reagents and consumables of the tests. Next, we will evaluate several collections of compounds: a library of 1500 FDA-approved compounds; all collections of natural and synthetic molecules from CIBFar / CEPID-FAPESP (which include compounds from NuBBE / IQAr / UNESP /, FCFRP / USP, LSPN-DQ-UFSCar and IQ / UNICAMP); the PITE-FAPESP / MMV / DNDi / Unicamp / USP Consortium; NEQUIMED / IQSC / USP. Fluorescent peptide probes and protease inhibitors, produced at EPM / UNIFESP, will be produced and evaluated in phenotypic and enzymatic assays, based on previous studies on the SARS-Cov coronavirus cysteine ​​protease and also the human TMPRSS2 serine protease, involved in the invasion by COVID-19. Compound libraries from the international organization Medicines for Malaria Ventures will be made available for screening against SARS-Cov-2 in this project: they are libraries ranging from 400 compounds (Pathogen Box and Pandemic Box) to 20-40,000 or up to 150,000 compounds with great chemical diversity . All relevant SARS-Cov-2 coronavirus proteins as potential targets for antiviral drugs will be cloned and expressed in recombinant form in E. coli, and biochemical and biophysical assays will be developed to identify inhibitors and ligands. The identification of hits against SARS-Cov-2 will be important not only for their future development as candidates for new antiviral drugs, but knowledge of their chemical structures can immediately assist us in the emergency effort to reposition drugs already in clinical use for other therapeutic indications, by comparing their active pharmacophoric groups and bioisosterism methods. With the possibility of the emergence of immune escape mutants, the sequencing of SARS-CoV-2 genomes and viral isolation will be carried out during the period of the pandemic occurrence in Brazil to identify possible escape mutants in the receptor binding region. On another research front, simple and alternative synthetic routes will be developed for drugs already approved for use in humans and which are being identified as effective, albeit partially, in the treatment of COVID-19.",2020,2022,Universidade de São Paulo,73624.43,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +C06343,2020/05146-7,Development of anti-SARS-CoV-2 vaccine using VLPs,"The emerging SARS-CoV-2 virus appeared in China, with easy spread and significant lethality. In less than three months of its identification it has already caused more than 30,000 deaths worldwide and with an increasing number of fatalities. As it is a new virus introduced into the human population, there is no immune population; it has easy spread and lethality varies from 1 to 16% according to country, age group and comorbidities. In the absence of a specific vaccine or treatment, the pandemic is paralyzing entire continents. In this project, we aim to use the vaccine platform based on virus-like particles (virus like particles, or VLP) conjugating peptide sequences from SARS-CoV-2 to Q²VLPs and VP1VLPs from Spike protein using them as a mechanism for delivering peptide antigens to the components immune system cells. It is worth mentioning that this project was quickly adapted for the development of an effective and safe vaccine against SARS-CoV2 to the Young Researcher project, Process number: 2019 / 14526-0. Because of this, we are already working on selecting the best antigens to be conjugated to VLPs due to the enormous urgency that this historic moment demands of us.",2020,2022,Universidade de São Paulo,70679.96,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C06344,2020/04899-1,Interaction of SARS-CoV-2 Surface Protein (Spike Protein) with Heparin: Therapeutic Potential,"Currently, there are no drugs commercially available and / or designed to treat and prevent infections associated with the new SARS-CoV-2 coronavirus outbreak. Traditionally, drug development has been slow and ineffective against these threats to public health. Therefore, the redirection of existing medications capable of preventing and treating new coronavirus infections is a timely and very attractive alternative. Heparin, a well-tolerated anticoagulant drug, has been used safely in medicine for more than 80 years and, together with its anticoagulant and anti-inflammatory activities, has a known ability to prevent viral infections, including coronavirus. Preliminary data show that SARS-CoV-2 Surface Protein (Spike Protein), the protein responsible for infection of host cells, binds to heparin. Also, high mortality rates due to COVID-19 are associated with coagulopathy and hypercytokininaemia (cytokine storm). Therefore, this project aims to study and explore the structural properties of heparin that mediate such interaction as proof of concept for the development of heparin-based antiviral drugs.",2020,2022,Universidade Federal de São Paulo,72280.56,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C06345,2020/04738-8,Patients with severe acute respiratory syndrome due to Covid-19 in an Emergency Department,"The current Covid-19 pandemic has affected more than 920,000 people and killed more than 46,000 worldwide. Most affected patients have a mild condition, but a small percentage, from the percentage point of view, but large in absolute numbers, may have a severe acute respiratory syndrome (SARS), with fever, cough, pulmonary infiltrates and hypoxemia, and may progress for respiratory failure and need for mechanical ventilation. The Emergency Service of Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HCFMUSP) is the current reference center for the treatment of patients with the most severe form of the disease. Our team is responsible for the initial care of these patients and, therefore, is well positioned to produce the necessary knowledge for a better understanding and treatment of this disease. In this way, we created this project, which consists of four subprojects. The first subproject aims to determine whether serum markers of the inflammatory response can predict, alone or in combination, the evolution of patients with SARS by Covid-19 for respiratory failure. The second seeks to determine whether pulmonary ultrasound is a viable alternative for assessing respiratory function in these patients. The third is a clinical trial with a drug already used in other clinical situations and which may be useful in preventing respiratory failure in patients with Covid-19 pneumonia. Finally, the fourth focuses on statistical and stochastic models, which can improve and guide the care of these patients. The study will be conducted at the Emergency Service of HCFMUSP, which is the gateway to the vast majority of patients with SARS by Covid-19. Patients with severe acute respiratory syndrome who do not require mechanical ventilation at admission will be included. In subprojects 1 and 2, these patients will only be followed up, without intervention, performing laboratory and ultrasound exams. In subproject 3, patients will be divided into two groups, one receiving NAC and the other placebo. In all three subprojects, the outcome will be mortality and the need for mechanical ventilation. In this pandemic moment, the search for a better understanding of the disease and treatments that can reduce the need for mechanical ventilation in these patients is extremely urgent and these are exactly the objectives of our project.",2020,2022,Universidade de São Paulo,19210.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C06346,2020/05256-7,Epitopes mapping of SARS-CoV-2 virus to T lymphocytes and Spike protein receptor to B lymphocytes,"The emerging SARS-CoV-2 virus appeared in China, with easy spread and significant lethality. In less than three months of its identification it has already caused more than 35,000 deaths worldwide and with an increasing number of fatalities. As it is a new virus introduced in the human population, it is not known if there is an immune population; it has easy spread and lethality varies from 1 to 16% according to country, age group and comorbidities. In the absence of a specific vaccine or treatment, the pandemic is paralyzing entire continents. The entry of all coronaviruses into host cells is known to be mediated by the glycoprotein Spike, a potential therapeutic target, especially the region of the receptor receptor domain. The knowledge of the cellular response to this virus is still little known. Therefore, this knowledge is of immediate relevance. In this project, we aim to map the epitopes of T and B lymphocytes recognized by cells and antibodies of convalescent COVID-19 patients, starting from the complete sequence for T epitopes and focusing on the Spike protein receptor for B lymphocytes. These data may assist in the development of vaccines and immunotherapeutics in the medium term.",2020,2022,Universidade de São Paulo,71132.58,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C06347,2020/05984-2,Acute neurological manifestations associated with the SARS-CoV-2 virus,"In 2019, an outbreak of respiratory disease associated with a new coronavirus, SARS-CoV-2, began in the city of Wuhan, China. Since then, this highly transmissible virus has motivated extreme isolation measures around the world, in an attempt to mitigate the infection of entire populations, concomitantly saturating medical services and collapsing health systems. Several coronaviruses are associated with neurological syndromes such as encephalitis, myelitis and Guillain-Barré syndrome, among them SARS-CoV-1, phylogenetically the human coronavirus closest to SARS-CoV-2. Thus, it is expected that similar manifestations affect patients in the current epidemic. OBJECTIVES: To characterize the epidemiological, clinical, laboratory, electrophysiological and radiological profile of patients affected by myelitis, encephalitis and / or acute peripheral polyneuropathy in the presence of an epidemic associated with the SARS-Cov-2 virus. METHODS: This is a prospective observational study, which will evaluate the epidemiological, clinical, laboratory, electrophysiological and radiological characteristics of patients diagnosed with encephalitis, myelitis and / or acute peripheral polyneuropathy during the SARS-Cov-2 epidemic period, assisted in co-participant institutions. Patients who are considered suspected cases of SARS-CoV-2 will be selected according to criteria defined by the Ministry of Health (MS) and the World Health Organization (WHO) in the presence of proven community transmission, who present concomitant or subsequent clinical suspicion (up to 60 days after an event associated with SARS-CoV-2) of viral encephalitis, viral myelitis and / or acute peripheral polyneuropathy.",2020,2020,Universidade de São Paulo,31790.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Disease pathogenesis,2020 +C06348,2020/05211-3,Evaluation of amphiregulin as a prognostic biomarker of severity and its participation in the pathophysiology of COVID-19,"The latest threat to global health is the ongoing outbreak of the respiratory disease that has been named Coronavirus Disease 2019 (COVID-19), which is caused by the virus called SARS-CoV-2. Although scientists in basic and clinical areas worldwide are making great efforts to understand the pathophysiology and investigating the effect of drugs with antiviral action and the repositioning of drugs that have anti-inflammatory action, there is still no specific drug or effective clinical treatment. for COVID-19. However, it is known that progressive respiratory failure caused by massive damage to alveolar cells, resulting from viral replication and excessive local inflammation, is one of the major obstacles to the recovery of critically ill patients with COVID-19. In this sense, the host's defense against infections depends not only on the mechanisms of immune resistance, but also on the body's ability to tolerate the damage that a given pathogen promotes. Amphiregulin (AREG) is a central factor that promotes repair and restoration of tissue integrity after tissue damage associated with inflammation. AREG-deficient animals have a substantial impairment of the ability to restore lung function in infection models. In addition, the administration of recombinant AREG enhances the tissue repair process after tissue injury resulting from excessive inflation. Our working hypothesis is that AREG plays a key role in repairing and restoring the integrity of lung tissue during COVID-19 and that treatment with recombinant AREG shortens patients' recovery period. In addition, we work with the hypothesis that the determination of AREG levels in patients still in moderate form can be an important prognostic biomarker of severity in patients. Thus, we propose in the present project to conduct a translational study to investigate the participation of AREG in the pathophysiology of COVID-19, using animal models of experimental SARS-CoV-2 infection and samples from patients diagnosed with COVID-19. In addition, we intend to assess the potential of AREG as a prognostic biomarker of severity in patients with COVID-19.",2020,2020,Universidade de São Paulo,69381.02,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C06349,2020/04705-2,Diagnostic and prognostic study of SARS-CoV-2 infection and influenza virus,"Introduction: The epidemics caused by the Influenza virus are recognized for their great impact on public health. The identification of a new coronavirus strain (SARS-CoV-2) with pandemic spread has brought new challenges for diagnosis, control and therapy. The rapid and low-cost diagnosis of SARS-CoV-2 and Influenza infections may allow the adoption of measures to control transmissibility both in the environment of Health Units and isolation from social contact in the community. The early identification of patients with a higher risk of death also allows a targeted therapeutic approach with ventilatory support measures and the use of specific antivirals against these two viruses. The understanding of pathophysiological mechanisms related to the coagulation cascade, involved in the severe forms of involvement by respiratory viruses, proposed in this project, may lead to the development of new therapeutic possibilities in order to reduce the high lethality of this serious clinical situation. Objective: 1) Development of a method for rapid and low-cost diagnosis of SARS-CoV-2 and Influenza virus infections; 2) study of early prognostic factors in patients diagnosed with SARS-CoV-2 infection and Influenza virus; 3) Study of platelet aggregation levels by Multiplate-ADP and coagulation in hospitalized patients due to respiratory distress. Method: 4 groups will be compared: SARS-CoV-2 infection patients, Influenza virus infection patients, influenza syndrome patients with negative tests for COVID-19 / Influenza virus and healthy controls. Patients with suspected flu-like symptoms (fever accompanied by one of the following symptoms: cough, sore throat, runny nose, frontal headache with onset of symptoms in the last 7 days) will be enrolled in 2 public referral hospitals. Exclusion criteria: Age below 18 years. The healthy control group will consist of 50 volunteer health care professionals paired by sex and age to the group of patients with SARS-CoV-2 infection. Peripheral blood, skin imprint and saliva samples will be collected from all individuals included in the study. Those who require hospitalization and present criteria for severe acute respiratory syndrome (SARS) will also be collected second and third samples of non-invasive specimens (skin imprint and saliva) 3 and 7 days after inclusion. Nasal flush will be collected for diagnosis of Influenza virus and SARS-CoV-2 infection by the protocol only for those who do not perform these tests through the hospital routine. All samples will be sent for storage (- 80C) at the Virology Laboratory of USP's Institute of Tropical Medicine and UNICAMP's Innovare Laboratory. Metabolites will be studied by plasma mass spectrometry, skin and saliva imprint and analyzed by artificial intelligence. The diagnosis of infection by Influenza virus or SARS-CoV-2 will be considered positive (gold standard) by positive molecular biology test in a nasal wash sample. Patients' prognosis will be assessed by the following outcomes: length of hospital stay, need for dialysis, need for orotracheal intubation or hospital death. Platelet aggregability will be studied using the Multiplate-TRAP and Multiplate-ASPI methods, reticulated platelet levels (young), mean platelet volume (MPV), P-selectin, D-dimer, PAI-1, Fibrinogen, Tromboxane, Tempo activated partial thromboplastin (PTTa), prothrombin time (TP); Type B natriuretric peptide (BNP); Ultrasensitive troponin, peak glycemia during hospitalization, lipid profile when hospitalized.",2020,2022,Universidade de São Paulo,35023.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06350,2020/04558-0,Caracterização de fatores de risco intrínsecos e o desenvolvimento de novas alternativas de diagnóstico e tratamento para COVID-19 [Google Translate : Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19],"The arrival of SARS-CoV-2 in Brazil in March 2020 had a negative impact on the economy, generated panic in the population and disrupted our country's public and private health systems. It is evident the need for methods of rapid diagnosis / prognosis and alternative therapies that help to face this pandemic in our country. Thus, this multidisciplinary project, which involves researchers from several units at Unicamp and other research institutions in Brazil and abroad, aims to use clinical specimens (nasopharyngeal swab, serum and frozen whole blood) already used in the diagnosis and other routine examinations and stored at the Clinical Pathology Laboratory of HC to: (1) Assess the circulation and genetic diversity of Covid-19 in Campinas; (2) Search for biomarkers that help us in the rapid diagnosis or in the prediction of fatal cases, using methodologies of proteomics, metabolomics and multiplex immunoassays; (3) Identify new antivirals through the repositioning of drugs already approved for use in humans, in addition to the discovery of new drug candidates, by computer screening tests and antiviral activity test in cell culture in a level 3 biological containment laboratory.",2020,2022,Universidade Estadual de Campinas,34960,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +C06351,2020/04522-5,Clinical Trial for Bradykinin Inhibition in Adults Hospitalized with Serious COVID-19,"The pandemic of the new severe acute respiratory syndrome virus (SARS-CoV-2) has already been confirmed in more than 330 thousand people, being responsible for more than 14 thousand deaths worldwide (World Health Organization - official data of 23 March 2020). The current treatment for severe cases is based on respiratory support, use of a variety of antibiotics with possible extracorporeal oxygenation; however, the results are still unsatisfactory. Researchers have shown that the virus binds to Angiotensin-Converting Enzyme 2 (ECA2) to gain access to cells. This enzyme is essential in the inactivation of Angiotensin II (ANGII) and bradykinin. The accumulation of bradykinin in the lungs is a common effect after the use of ACE inhibitors with a consequent increase in cough. In studies with animal models, inactivation of ACE2 leads to severe pneumonitis after administration of lipopolysaccharides (LPS) and inhibition of bradykinin completely restores lung function and structure. As pneumonia is the most intense condition and a marker of disease progression, our hypothesis is that the increase in bradykinin is the main link between SARS-CoV-2 infection and ACE2 inhibition resulting in a severe respiratory syndrome. OBJECTIVE: To evaluate the efficacy of two pharmacological inhibitors of bradykinin, the C1 esterase / kallikrein inhibitor (Berinert®, CSL Behring GmbH) and the bradykinin receptor 2 inhibitor, icatibant (Firazyr®, Shire) in critically ill patients hospitalized for SARS -CoV-2. METHODOLOGY: This is an open randomized clinical trial to be carried out at Hospital de Clínicas, Universidade Estadual de Campinas, Brazil. One hundred and eighty patients will be divided in a 1: 1: 1 ratio to receive: i, the basic support established by published clinical trials, which include oxygen support, invasive and non-invasive mechanical ventilation, use of antibiotics, use of vasopressors and therapy renal support; or, ii, Berinert, 20 U / Kg intravenously, one dose on the day of inclusion in the study and one dose on the fourth day; patients in this group will receive the same basic support procedure offered to the control group; iii, Firazyr, 30 mg subcutaneously 8/8 h for four days; patients in this group will receive the same basic support procedure offered to the control group. The primary end points are, complete recovery with hospital discharge or death; monitoring will be done for 28 days. The inclusion criteria will be: men and women aged 18 years or older with positive RT-PCR for SARS-CoV-2; pneumonia confirmed by computed tomography (CT) of the chest; oxygen saturation in ambient air of 94% or less. Exclusion criteria: Pregnant or lactating women; patients with severe liver disease (alanine aminotransferase and / or aspartate aminotransferase> 5x above normal); severe nephropathy (kidney transplant or dialysis), HIV infection, cancer, hereditary angioedema, other immunodeficiencies, past myocardial ischemic disease, past thromboembolic disease. All study patients and / or their relatives will be informed about the research objectives and risks and should read and sign the Informed Consent Form.",2020,2022,Universidade Estadual de Campinas,73624.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C06352,2020/05204-7,Prospective evaluation of the production of lipid mediators in the immune response against COVID-19: search for biomarkers and new therapeutic targets in the evolution of the disease,"Due to the great spread of the new SARS-COV-2 coronavirus, we are experiencing a pandemic. COVID-19 disease, caused by this coronavirus, can have moderate to severe complications, especially in male, elderly and / or patients with underlying diseases. Severe cases have a ""cytokine storm"", with an exacerbated inflammatory response in the lung, the organ most affected. This project therefore seeks to identify molecular factors of susceptibility and resistance, as well as biomarkers of susceptibility and clinical evolution in COVID-19. To this end, we will investigate the inflammatory profile of patients by detecting and quantifying lipid mediators, including eicosanoids, steroid hormones and compounds derived from sphingolipids and ceramides, to seek a possible association with the clinical outcomes of COVID-19 and with components of the immune response, such as cytokines , chemokines and N-glycans profiles of IgE Ecs. In a case-control study approach, control participants (non-infected and asymptomatic) and patients treated at Hospital São Paulo in the city of Ribeirão Preto will be recruited, who will be evaluated clinically and laboratory by the doctors responsible for the care; evidence of infection with SARS-COV-2 will be made in all participants. Plasma and leukocytes (buffy coat) will be obtained from the blood of participants. Protein inflammatory mediators will be quantified in plasma, as well as eicosanoids, steroid hormones, sphingolipid-derived compounds and ceramides. Therefore, through the use of mass spectrometry, we propose a multidisciplinary approach to identify lipid biomarkers related to the inflammatory process in COVID-19. The profiles of N-glycans in the IgG Fcs will be evaluated, according to the team's previous experience. The cells obtained will be frozen in Trizol, for subsequent RNA extraction and analysis of gene expression. With these results, it is expected to understand in more detail, the pathophysiology of COVID-19, to establish markers of disease evolution and morbidity, as well as new targets for therapeutic interventions in patients infected with SARS-VOC-2.",2020,2022,Universidade de São Paulo,70932.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Pre-clinical studies",2020 +C06353,2020/05204-7,Development of protein nanovacins that self-structure against SARS-Cov-2,"The sudden appearance of a new viral pneumonia in China at the end of 2019 was the beginning of a series of events that took the world to a pandemic that in three months infected more than a million people around the world and reached more than 200 countries and territories. The SARS-CoV-2 virus, from the same Coronaviridae family to which the SARS and MERS viruses belong, triggers a severe acute respiratory condition that leads to death in approximately 2% of cases. The COVID-19 disease has already generated immeasurable global impacts and it is believed that it will only be properly contained through the development of vaccines, since we can face new waves of dissemination when suppression measures are suspended, which makes vaccines a top priority. according to the World Health Organization. In a scenario so fragile that it involves the need to give priority vaccination to risk groups, it is necessary to prioritize safer vaccination strategies, such as subunit vaccines. The low immunogenicity frequently observed in this strategy can be countered with the use of nanoparticles that allow a multivalent presentation of antigens, thus generating a more robust immune response. In this project, we propose the use of SAPN (Self Assembling Protein Nanoparticles) nanovaccines, in which the protein antigen is modified by the fusion of short peptide sequences that self-structure in nanoparticles (NPs) of approximately 100 nm under physical-chemical conditions appropriate. Such an approach mimics the disposition of antigens from a viral particle and has already been used in our group in a Zika model, inducing a strong antigen-specific humoral response. Different SARS-CoV-2 structural antigens will be selected to be transformed into nanovacins by the proposed strategy, which will be used to induce immune responses (antibodies) with the ability to inhibit viral infection in vitro for subsequent tests in a murine model. As additional advantages, these nanovacins have better stability and high internalization capacity, as they have peptides that act as membrane-active peptides, thus mimicking characteristics of size and behavior typical of the viral particle, which may even favor cellular immunity. We therefore hope to develop an innovative vaccine strategy that can significantly contribute to this epidemic and will soon be considered a promising tool to limit the progress of COVID-19.",2020,2022,Universidade de São Paulo,67388.83,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06354,2020/05040-4,Translational study on the role of pro-resolution lipids as mediators of tolerance to SARS-CoV-2 infection,"The pandemic of the new coronavirus, COVID-19, caused by the SARS-CoV-2 virus, has been causing an unprecedented number of hospitalizations and deaths worldwide, which seems to be far from over. The high transmissibility and the absence of vaccines and effective therapies against this infection, combined with the need for mass intubation of patients in respirators in ICU beds, composes a tragic scenario where the consequence has been the collapse of public health systems in several countries. countries. The first reports and clinical studies published recently, clearly point to diabetes (type 1 or 2), as one of the main risk factors for death from COVID-19. For these reasons, it is essential and urgent that we deepen our understanding of the mechanisms that make the diabetic, a patient more vulnerable to the severe form of this disease. The first studies investigating the pathology of the disease, indicate that the condition suggests an ineffective process of resolving the inflammatory process caused by the virus. Pro-resolution lipid mediators (MLPRs) are lipids that have the function of resolving inflammation, and are known to be reduced in obese / diabetic patients, as well as in murine models of obesity. For this reason, our hypothesis is that diabetic patients are more vulnerable to the inflammatory process due to SARS-CoV-2 infection, due to their low levels of MLPRs and, therefore, due to their low ability to resolve inflammation in the pathways. aerial views of patients. In this project, we propose a translational research strategy, aiming to achieve 3 main objectives: (1) to determine the correlation between the plasma levels of MLPRs with inflammatory and clinical markers of patients infected with the new coronavirus; (2) identify, through in vitro assays, MLPRs with the greatest protective effect on the pulmonary epithelium infected with SARS-CoV-2; and (3) to evaluate, in an in vivo study with a murine model of metabolic syndrome, the protective effect of MLPR on the inflammatory process and lung damage caused by SARS-CoV-2 infection.",,,Universidade de São Paulo,65203.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C06355,2020/04919-2,Determining molecular candidates that contribute to the high risk of COVID-19 in elderly individuals,"COVID-19 has recently emerged as an age-related disease whose mechanisms are still poorly understood. Using a combination of hypothesis-driven and unsupervised data-based approaches, as well as patients and preclinical models, we hope to find proteins and candidate pathways that can not only predict disease susceptibility, but also unravel the molecular mechanisms through which aging contributes to SARS-Cov-2 infection. We also hope to propose drugs approved by the FDA and ANVISA that can potentially target these pathways to prevent, mitigate or eliminate viral infection. Our general objective is to elucidate how aging constitutes the main risk factor for COVID-19, providing possible solutions for its pandemic.",2020,2022,Universidade Estadual de Campinas,30598.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies,2020 +C06356,2020/04505-3,"Mapping the spread of SARS-CoV-2: size of the outbreak, transmission dynamics, clinical outcomes of the infection and duration of antibody responses in a small Amazonian city","The SARS-CoV-2 virus has spread globally and now represents an important challenge for low- and middle-income countries, where health infrastructure can quickly become overburdened. This proposal is part of our ongoing field research, funded by FAPESP, to investigate the epidemiology and control of SARS-CoV-2 infection in Mâncio Lima, a small Amazonian city. The general objective is to translate the information generated by the field study into evidence to guide the control of COVID-19 in one of the poorest regions of Brazil. We start from the hypothesis that many SARS-CoV-2 infections remain unnoticed and asymptomatic carriers of the infection may continue to spread the pathogen in their daily social interactions until its spontaneous elimination, becoming immune to reinfections or, at least, to serious illness. . The proposed means to test this hypothesis are: (a) to use serial serological assays to retrospectively detect seroconversion events, estimate the size of the SARS-CoV-2 outbreak and identify risk factors associated with seroconversion in the community; (b) identify social interactions and shared spaces, such as home, workplace, schools and churches, that may have contributed to the local transmission of SARS-Cov-2; (c) calculate the proportion of SARS-CoV-2 infections diagnosed retrospectively that remained asymptomatic or had mild symptoms, usually without prior diagnosis, and those associated with the disease (COVID-19), resulting in visits to health services and even even in hospitalization, and (d) determining the proportion of individuals who, when they become seropositive during the outbreak, remain with antibodies to SARS-CoV-2 over the next 12 months.",2020,2022,Universidade de São Paulo,73568.19,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C06357,2020/04583-4,Impact of intestinal microbiota and its metabolites on SARS-Cov-2 infection,"The Covid-19 pandemic has impacted public health dramatically in several countries. In this context, understanding the factors related to the severe forms of Covid-19 is essential for the prevention and, possibly, treatment of those infected. Recent work shows that the intestinal microbiota and its products play a fundamental role in respiratory infections by other viruses including respiratory syncytial virus and Influenza virus. However, it is not known whether there is a relationship between changes in the microbiota and infection by COVID-19. In this project we will use experimental approaches already used by the group to understand the relationship between intestinal microbiota / its products and respiratory viral infection. We will soon use animal models in which we alter the intestinal microbiota and its metabolite production through the use of antibiotics, supplementation with microbiota metabolites or diets that alter the endogenous production of these products and we will analyze your response to SARS-CoV-2 infection. . Mice kept under different experimental conditions (diets, oral supplementation with metabolites or antibiotics) will be infected with SARS-CoV-2 and analyzed for disease progression (weight variation and clinical signs) and subsequently euthanized for analysis of viral load, inflammatory, cellular mediators, and histological changes in the lung. In addition, we will analyze the amount of virus present in the feces and the intestinal production of short-chain fatty acids and the composition of the intestinal microbiota. The data obtained will be complemented by analyzes performed with human cell lines and samples from infected patients.",2020,2022,Universidade Estadual de Campinas,31944.7,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06358,2020/05289-2,Modeling of COVID-19 in vitro and in silico,"The new coronavirus SARS-CoV-2 emerged in December 2019 in China and spread to several countries, causing an acute respiratory disease called COVID-19 (Coronavirus disease 2019). COVID-19 can evolve into severe respiratory infections resulting in a high death rate for individuals over 60 and also patients with chronic diseases, such as diabetes and cardiovascular diseases. COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. At a time when the COVID-19 pandemic is expanding globally, we saw the opportunity to contribute our expertise in two distinct but closely related strands with research projects developed by our group: 1) development of a platform to model SARS-CoV-2 infection in vitro using 3D bioprinting; and 2) production of an in silico model for studies of the spread of contagion by SARS-CoV-2 in Brazil. We propose a multidimensional study that aims to provide tools that can be used for in vitro studies of infection and drug tests, and an in silico model for assessing and predicting the impact of COVID-19. Once validated, the in vitro models will be available for use by researchers who are interested in studying mechanisms of pulmonary and cerebral infection, new treatments to combat infection by SARS-CoV-2, among other possibilities. The in silico modeling of the COVID-19 pandemic may be an important tool for the establishment of public policies to face the pandemic, both in aspects of collective health and in the mitigation of social and economic impacts.",2020,2022,Universidade Federal de São Paulo,70226.37,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +C06359,2020/04836-0,"Clinical and epidemiological study of SARS-CoV-2 in a prospective population and hospital cohort in São José do Rio Preto, São Paulo, Brazil, during a 2020 pandemic","In a global context, COVID-19 is the biggest health threat today. In just over four months, SARS-CoV-2 has spread to 171 countries reaching pandemic status. Most patients with COVID-19 have a mild course of the disease, however, approximately 20% develop severe disease with a high mortality rate that are associated with advanced age, comorbidities and immunosuppression. Epidemiological studies help to reveal the extent of viral spread in homes, communities and hospitals. Thus, preventive and control measures can be established by the authorities. This project proposes to use a pre-established population cohort containing four years of data collection on the participants. The cohort is carried out in a restricted neighborhood in the municipality of São José do Rio Preto, present in the northwest region of the state of São Paulo. To this end, active participants in this study will be monitored for the appearance of symptoms related to COVID-19. A quick access number to the team will be made available in case of acute symptoms and, if necessary, referral to the local health service. Monitoring of hospitalized patients at the Hospital de Base, Faculty of Medicine of São José do Rio Preto (FAMERP), who are suspected or confirmed by COVID-19 will also be carried out. Samples will be collected for further analysis of pro-inflammatory cytokines, possible biological markers that indicate worsening of the disease.",2020,2022,Faculdade de Medicina de São José do Rio Preto - SDE,71610.24,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis,2020 +C06360,2020/05497-4,A reagent-free viral detection platform,"This is a proposal that involves a Joint Partnership (JP) between the University of São Paulo (USP) and the University of the State of São Paulo (UNESP) and will mainly focus on research on the development of portable electrochemical diagnostic devices for the detection viral infections of relevance to Brazil (flavivirus) and worldwide (SARS-Covid-2) using capacitive methods without reagents, already proven viable (in our thematic project) to detect DENV infections in serological samples from infected patients. Therefore, we are including in this proposal the use of this platform to diagnose COVID-19. The proposal provides for the use of a potentiostat the size of a pen-drive that can be attached to cell phones. The biggest challenge is to develop robust, reagent-free sensors for this type of device, which can effectively enable an electronic means of virus surveillance worldwide. The proposal is focused on overcoming the challenge of sensor manufacturing.",2020,2020,Universidade Estadual Paulista (Unesp),71863.56,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Other,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06361,2020/04579-7,Study on risk factors associated with greater severity to COVID-19 and mapping of metabolic pathways required for the anti-SARS-CoV-2 response,"The pandemic of the new severe acute respiratory syndrome virus (SARS-CoV-2) has been confirmed in more than 700,000 people on all continents and has been responsible for more than 20,000 deaths worldwide (World Health Organization - official data of March 27, 2020). The only way to treat severe cases is through respiratory support with still unsatisfactory results. To date, there is no efficient pharmacological treatment to modify the natural history of evolution of COVID-19, which results in the mortality of approximately 2% of diagnosed patients, with more than 20% of these progressing with reduced O2 saturation below 94 % and pneumonia. Although the mechanism of action of SARS-CoV-2 is still not completely clear, some groups appear to be more susceptible to the severe form of this infection. Among them are people with pre-existing medical conditions, mainly disorders related to glucose homeostasis (diabetes) and age (hypertension, heart disease, lung disease, cancer and diabetes) and elderly people. SARS-Cov-2 is known to infect pulmonary epithelial cells and macrophages. Still, different viral families, when infecting target cells, alter cellular metabolism, inducing pathways favorable to its replication. This makes the modulation of specific metabolic pathways extremely promising to induce the production of interferons and improve the antiviral response, resulting in a decrease in viral load. In this project we aim to determine the metabolic pathways with therapeutic potential for the treatment of SARS-CoV-2 that interfere with viral replication and with the induction of interferons and to identify the factors responsible for the greater severity of COVID-19 in diabetic patients. With this study we hope to obtain clarification on the mechanisms related to SARS-CoV-2 infection so that better treatments are available to the population in order to control the spread of the disease and improve the quality of life of infected individuals.",2020,2022,Universidade Estadual de Campinas,72590.64,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C06362,2020/05367-3,Use of convalescent donor plasma to treat patients with severe SARS-CoV-2 infection (COVID-19),"The SARS-CoV-2 virus pandemic affects the whole world and has now reached Brazil. The magnitude and consequences of the COVID-19 epidemic in the country are still unknown. In this study, we will assess the impact of COVID-19 convalescent plasma transfusion in patients with severe clinical presentation of this disease. The clinical picture of SARS-CoV-2 infection is heterogeneous, with a mild and oligosymptomatic clinical presentation, or even asymptomatic, in most cases, but a portion of patients has a severe evolution, with respiratory failure, responsible for most deaths. To date, there is no specific therapy for COVID-19. A potentially promising alternative is the infusion of preformed antibodies, coming from convalescent individuals of COVID-19. This form of therapy, through the infusion of serum or plasma, is the only way to confer immediate immunity, until the affected organism itself has time to mount its own immune response (adaptive immunity). The first reports of this treatment modality date back almost a century, to treat diseases such as polio, measles, mumps and influenza. More recently, in 2009 and 2010, convalescent serum was used to treat patients with severe H1N1 influenza, in which the group of transfused patients (n = 20) was shown to have a lower mortality rate than that observed in the group not transfused (n = 73) (20.0% vs 54.8%; P = 0.01). In addition, the group of transfused patients had a viral load and levels of inflammatory cytokines (IL-6, TNF ±) on days 3, 5 and 7 significantly lower than those observed in the group of non-transfused patients (P <0.05). The first coronavirus epidemic (SARS-CoV), which also originated in China, in 2002 and 2003, provided information regarding the feasibility of using convalescent plasma, in which antibodies neutralizing the virus were identified. The second coronavirus epidemic occurred in the Middle East, in 2012, and then in South Korea. In both epidemics, the mortality rate was very high. Eighty patients with severe acute respiratory syndrome caused by coronavirus were treated with convalescent plasma, with a more favorable clinical outcome in transfused patients. Plasma was obtained from convalescents from the seventh day of their recovery, so that they contained high antibody titers. A recent meta-analysis suggested that convalescent plasma transfusion reduced mortality in groups of patients with severe acute respiratory syndrome caused by viral, coronavirus and Influenza virus. The authors identified 32 studies, mostly of low methodological quality and with a high risk of bias. The hypothesis is that transfusion of plasma from convalescent donor of COVID-19 could result in a more favorable clinical evolution and increase the survival rate of individuals with severe involvement by the disease. Forty patients with the severe form of COVID-19 will be treated with convalescent plasma, whose outcomes will be compared with a control group consisting of 80 patients with the same disease, with similar characteristics and clinical severity. Each patient will receive an approximate dose of 10 mL / kg / day of convalescent plasma (600 mL / day for adults), for 3 consecutive days. The main objective is to compare the survival curve between the two groups until the 30th and then until the 60th day of randomization in a group of patients with COVID-19 treated with convalescent plasma from this infection with that observed in a group of patients undergoing conventional (supportive) treatment. The most important secondary objectives are to assess viral load, the influence of age on the survival rate and the occurrence of possible adverse reactions to plasma transfusion in both groups.",2020,2022,Universidade de São Paulo,30562.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C06364,2020/04635-4,Development of a simple and low-cost device for the rapid diagnosis of the new coronavirus (SARS-CoV-2),"With the recent pandemic caused by the new coronavirus (SARS-CoV-2), the early diagnosis and isolation of infected patients have become essential measures to reduce and delay viral spread. However, the insufficient number of diagnostic tests for the infection has greatly limited the ability of clinicians and public health specialists to accurately determine and track the prevalence, severity, mortality and transmissibility of this disease. In this project, it is proposed the development of a disposable, simple and low-cost microfluidic device for the detection of three RNA sequences of the SAR1-CoV-2 virus N1 gene, aiming at the quick and accurate diagnosis of COVID-19. The performance of our Research Group has been based on the development of devices like this for the detection of protein biomarkers aiming at the diagnosis of diseases with the partnership of Research Groups in the health area, which has generated important results with a strong impact on innovation. The construction of the proposed microfluidic platform will make use of easily accessible materials and simple equipment and will allow the analysis of different samples simultaneously. The device will consist of several microfluidic channels, each containing four independent sensor regions, which will allow detection by electrochemiluminescence of the three RNAs of the virus in addition to a human RNA, which will be used as the device's internal control. The applicability of the devices to be built will be evaluated initially in standard samples containing synthetic sequences (positive and negative) and, in a second moment, in samples from patients infected with SARS-CoV-2 provided by the UFSCar University Hospital. The project also aims at training human resources at different levels and publishing articles in national and international indexed journals as well as filing patents. Therefore, the development of a device for rapid, selective and low-cost detection of viral RNA will allow the early diagnosis of SARS-CoV-2 infection, while meeting an international public health need.",2020,2022,Federal University of São Carlos,51568.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06365,2020/05326-5,Aspectos genômicos e epidemiológicos COVID-19 nas populações nativas brasileiras [Genomic and epidemiological aspects COVID-19 in native Brazilian populations],"Native American populations have been in contact with European colonists exposed to a myriad of pathogens from which they have been isolated for more than 15 centuries, since their differentiation in Beringia. Examples abound of epidemics that plagued post-contact America, leading to the extinction of diverse peoples. Recent studies involving old and current samples show a decrease in genetic variability between 50% and 90% after the arrival of Europeans. The leading cause of death in Brazilian natives today is respiratory complications from infection. Therefore, given the current epidemic of COVID-19, it is important to study these historically vulnerable populations, contributing to a better understanding of the impact of epidemics (past and present) on these populations, and to investigate the existence of genetic differentiation. in these individuals related to the evolution of SARS-CoV-2 infection. The present project intends to study COVID-19 under the genomic and epidemiological aspects in 550 individuals belonging to two native populations, Tupiniquim and Guaraní-Mbyá, resident in Espírito Santo, with different levels of exposure to urban society. Given the extensive studies in these populations over the past few decades, it will be possible to assess the evolution of the epidemic, whether the response is related to the genetic profile of these populations and what the contribution of pre-existing clinical findings (i.e. tuberculosis, diabetes) is. In addition, it will be important to transfer the findings in these native individuals to assess whether the potential for infection may be related to native ancestry in the Brazilian population.",2020,2022,Universidade de São Paulo,74631.62,Human Populations,Other,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06366,2020/04860-8,Global genome screening with CRISPRko libraries to identify essential factors in SARS-COV2 infection and replication,"The present decade begins with a worldwide health emergency, the new coronavirus pandemic, the cause of severe acute respiratory syndrome 2 (COVID-19), also known as SARS-Cov2. To date, there are more than 900,000 positive cases that have resulted in more than 44,000 deaths in 180 countries. In view of these epidemiological data, strategies are needed to contain the transmission of the virus and mainly effective alternatives in the treatment of this disease. In this context, with the project we aim to assess the versatility of using a CRISPRko library to identify critical factors for SARS-Cov2 infection and replication. This library consists of a group of 77,441 guides directed to approximately 19 thousand human genes. This tool will allow us to globally screen the human genome, through CRISPR / Cas9-mediated gene deletion in human lung epithelial cells. After selection against essential genes for cell viability, we submitted the cells to five rounds of lethal infection with human isolate (from Brazil) of a SARS-Cov2 strain. Finally, we will be able to determine genes and pathways involved in viral replication and infection, by sequencing the surviving cells and detecting the guides present in that population. With this high coverage strategy, we believe that we will be able to point out new potential targets for the development of therapies for this disease.",2020,2022,Universidade de São Paulo,71176.44,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06367,2020/05270-0,Role of the death of human alveolar epithelial cells in the inflammation caused by 2019-nCoV and verification by transcriptome analysis of infected patients,"2019-nCoV infection results in pneumonia marked by intense inflammation. There is still no specific treatment for COVID 19 disease. The fact that 2019-nCoV infection causes intense pathological inflammation shows that surviving the infection is more a matter of tolerating lung damage (damage tolerance) than properly controlling the load viral (tolerance to the pathogen). New perspectives for the treatment of pneumonia involve host directed therapies, and should include therapeutic measures aimed at damage tolerance mechanisms. Lung damage in 2019-nCoV infection involves the destruction of pulmonary alveoli as a consequence of the death of infected alveolar epithelial cells, and the cytokine storm. Comorbidities, such as chronic lung diseases, obesity, hypertension, cardiovascular diseases, among others, aggravate the infection caused by the new coronavirus. This project has three well-defined objectives: i. To study the role of the death of human alveolar epithelial cells infected by 2019-nCoV, as direct mediators of macrophage activation; ii. Analyze the transcriptome of patients with or without comorbidities in order to relate the findings in vivo and in vitro; iii. Establish correlations between transcripts and comorbidities. These objectives are in line with the objectives of the Thematic Project under my coordination, aimed at investigating mechanisms that exacerbate asthma and acute bacterial pneumonia and diabetes and tuberculosis comorbidity. At the end of the development of the project, our purpose will be to list molecular targets to be investigated as pharmacological agonists or antagonists in immunotherapies directed to the host with COVID-19 with or without comorbidities, aiming at the damage tolerance. This project is a multicentric proposal, which results from the collaboration between FMRP-USP, FCFRP-USP and Hospital São Paulo de Ribeirão Preto, in a collective effort to better understand the immunopathology associated with COVID-19. The peripheral blood samples from patients and individuals from the control group will be shared to carry out different methodologies and the data collected will also be shared, featuring robust research and strengthening links of scientific collaboration.",2020,2022,Universidade de São Paulo,30929.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +C06368,2020/07247-5,"Diagnosis and monitoring of mutations in SARS-CoV-2, other viruses and opportunistic microorganisms that cause respiratory diseases in humans","The new coronavirus (SARS-CoV-2) has been identified as the cause of an outbreak of respiratory disease in Wuhan, Hubei province, China, as of December 2019 and has spread rapidly to an increasing number of countries. The World Health Organization (WHO) has declared SARS-CoV-2 infection as a pandemic. Efforts to contain the virus are underway; however, given the many uncertainties regarding the transmissibility and virulence of the virus, the effectiveness of these efforts is still unknown. Many molecular biology methods are being used for the diagnosis and surveillance of SARS-CoV-2. The detection methodology most used today is the polymerase chain reaction with reverse transcription (RT-PCR). Despite the great sensitivity, it is known that there are cases of false negatives, probably due to the loss or degradation of the viral RNA in the sampling process, or even mutation of the virus genome in the position of the primers and probes used. In addition, the demand for reagents for RT-PCR has increased considerably in the last few months, and there are not enough reagents being produced to meet global demand. The fraction of undocumented but infectious cases is a critical epidemiological feature that modulates the pandemic potential of an emerging respiratory virus. In addition, the test is specific for SARS-CoV-2, and does not test for other possible viruses that cause respiratory diseases, such as influenza. Therefore, the development of alternative methods, with high sensitivity, is essential to accompany the pandemic and the diversity of viruses and circulating strains.Next generation sequencing (NGS) provides a new and effective way to track samples and detect viruses without prior knowledge of the infectious agent. NGS strategies can provide additional confirmation, in addition to diagnosing other viruses, with strain specific discrimination in a single test. The monitoring of recurrent mutations in these viruses, including mutations in proteins responsible for the mechanism of entry into the host cell, has an impact on the understanding of pathogenicity and the composition of vaccines. The Centers for Disease Control and Prevention (CDC) in the United States annually uses information on genetic changes in influenza viruses to determine whether vaccines and antiviral drugs will work against current influenza viruses. The same monitoring should be used for the SARS-CoV-2 virus. In addition, with NGS it is possible to identify the airway microbiota and have a better prognosis for the evolution of the disease. Thus, understanding the associated microbiota can help to predict the outcome and reduce complications. Therefore, it is proposed here to use molecular biology strategies, such as new generation sequencing to diagnose viruses and bacteria that cause respiratory diseases and to monitor the mutational diversity of circulating strains. The evolution and rate of infection observed to date show an urgent need to develop public health activities to better understand the epidemiology of the new virus and characterize its potential impact on public health.",2020,-99,NGS Soluções Genômicas EIRELI - ME/NGS,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations", +C06369,2020/05023-2,BioApatIgG- Low cost and high performance serological diagnosis,"In December 2019, the World Health Organization was informed of a set of pneumonia cases of unknown etiology in Wuhan, China. Several subsequent investigations have identified a new coronavirus, now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in samples from affected patients. The highly sensitive and specific laboratory diagnosis is important for the rapid control of the evolution of Coronavirus disease associated with SARS-CoV-2 2019 (COVID-19). In Brazil, on February 26, the first patient with COVID-19 was diagnosed and registered. Since then, the curve of new cases has grown logarithmically and the demand for inputs for fast and accurate tests is a very important need. Currently, molecular tests for the detection of viral RNA in human fluids are recommended by the Center for Disease Control and Prevention (CDC). However, detection tests for monitoring people who have already developed immunity to the disease are of fundamental importance for real monitoring of viral progress. In Brazil, inputs for the production of both molecular tests and immunoassays are imported, and with the advance of the pandemic, the logistics of materials and high prices lead to the need for local production of biotechnological inputs for use in immunoassays and molecular tests. Given this, BIOLINKER, a company specialized in rapid protein synthesis with an in vitro transcription and translation system, proposes in partnership with Professor Ester Sabino of the Institute of Tropical Medicine and the Virology group at UFRJ of Professor Almidar Tanuri, to provide standardized ELISA reaction kits for the detection of circulating IgG against the COVID-19 virus in patient sera . Our results with the aptamer, validated during the PIPE phase 1, showed high affinity and specificity for the human IgG constant fraction. We foresee the use of this aptamer developed in PIPE-phase 1 of the 201722801-6 process conjugated with biotin and the detection through peroxidase conjugated with avidin which is another input easily produced by BIOLINKER. We will evaluate the detection of patient serum IgG against the nucleocapsid N antigens, the antigenic fraction of the spike protein RBS (spike receptor binding region). Our objective with this promotion is to establish a scale of production of the antigens that we are already screening in search of antigenic regions and that we initially produced in a ""cell-free"" or cell-free system, and then immobilize them in ELISA plates to the degree with a purity of 85%, in addition to manufacturing anti-IgG buffers and aptamer conjugated with biotin to detect IgG in the serum of patients in screening, together with the Institute of Tropical Medicine - FM-USP. Thus, we enable a fast and very low cost trial for epidemiological screening of the disease. Our estimated costs are low, since the production of aptamers is relatively low cost, as well as the production of antigen via ""cell-free"", since the company has its own expression plasmids and protocols already established. (AU) and then immobilize them in ELISA plates at a purity level of 85%, in addition to manufacturing buffers and anti-IgG aptamer conjugated to biotin for detection of IgG in the serum of patients being screened, together with the Institute of Tropical Medicine - FM-USP. Thus, we enable a fast and very low cost trial for epidemiological screening of the disease. Our estimated costs are low, since the production of aptamers is relatively low cost, as well as the production of antigen via ""cell-free"", since the company has its own expression plasmids and protocols already established. (AU) and then immobilize them in ELISA plates at a purity level of 85%, in addition to manufacturing buffers and anti-IgG aptamer conjugated to biotin for detection of IgG in the serum of patients being screened, together with the Institute of Tropical Medicine - FM-USP. Thus, we enable a fast and very low cost trial for epidemiological screening of the disease. Our estimated costs are low, since the production of aptamers is relatively low cost, as well as the production of antigen via ""cell-free"", since the company has its own expression plasmids and protocols already established. (AU) together with the Institute of Tropical Medicine - FM-USP. Thus, we enable a fast and very low cost trial for epidemiological screening of the disease. Our estimated costs are low, since the production of aptamers is relatively low cost, as well as the production of antigen via ""cell-free"", since the company has its own expression plasmids and protocols already established. (AU) together with the Institute of Tropical Medicine - FM-USP. Thus, we enable a fast and very low cost trial for epidemiological screening of the disease. Our estimated costs are low, since the production of aptamers is relatively low cost, as well as the production of antigen via ""cell-free"", since the company has its own expression plasmids and protocols already established.",2020,2022,Biolinker Biologia Sintética,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06370,2020/05023-2,Development of kits for the detection of COVID-19 by the RT-PCR multiplex method in real time and colorimetric by RT-LAMP,"The outbreak of the disease caused by the new coronavirus (COVID-19) was declared by the World Health Organization (WHO) a Public Health Emergency of International Importance and later as a pandemic. Worldwide, more than 50,000 deaths have been reported and despite worldwide efforts, there is still no vaccine or specific effective treatments. The strategy recommended by WHO to contain the progress of this pandemic consists of social isolation and the rapid identification of cases of infection. Therefore, diagnostic tests are extremely important and a demand of at least 15 million tests has been estimated by the Ministry of Health to supply the needs of Brazil. The virus nucleic acid amplification test (NAATs) using real-time RT-PCR is the diagnosis recommended by the WHO because it has high sensitivity and specificity, being able to detect the infection at the beginning. However, the reagents needed for this test, currently, must be imported and are scarce internationally due to the magnitude of the pandemic. Therefore, this project has as its initial and immediate objective the viability of a test for RT-PCR in real time multiplex totally produced in Brazil. Cellco currently produces 90% of the inputs needed to compose the standard test, being able to quickly validate and establish the complete kit and supply to centers able to perform the test. However, it is known that RT-qPCR tests are designed and require specific equipment and highly trained personnel, which represents another bottleneck in the ability to carry out mass tests. To overcome this other obstacle, we propose to establish a quick and simple test using the RT-LAMP technique. The application of this methodology for diagnostics has been highly explored because it is possible to adapt it to colorimetric tests with the sensitivity and specificity of other tests by nucleic acid amplification. Additionally, the test can be applied directly to clinical samples, without the need for nucleic acid extraction. Cellco already produces the base enzyme of the LAMP methodology, the DNA Polymerase I of Basillus stearothermophilus (Bst), in their native form and mutants that show greater processivity and resistance to common inhibitors in PCR reactions. We therefore propose the development of an RT-LAMP kit, its adaptation for colorimetric testing and making feasible for rapid coronavirus tests. This methodology is based on specific oligonucleotides, making it possible to maintain their sensitivity and specificity even with mutations and different strains of the virus. With this project, we intend, therefore, to quickly meet the national demand for the RT-qPCR standard test and in parallel to develop a rapid test using the RT-LAMP methodology that allows a large number of tests to be carried out to minimize the effects of the outbreak. COVID-19. (AU) its adaptation for colorimetric testing and feasibility for rapid coronavirus tests. This methodology is based on specific oligonucleotides, making it possible to maintain their sensitivity and specificity even with mutations and different strains of the virus. With this project, we intend, therefore, to quickly meet the national demand for the RT-qPCR standard test and in parallel to develop a rapid test using the RT-LAMP methodology that allows a large number of tests to be carried out to minimize the effects of the outbreak. COVID-19. (AU) its adaptation for colorimetric testing and feasibility for rapid coronavirus tests. This methodology is based on specific oligonucleotides, making it possible to maintain their sensitivity and specificity even with mutations and different strains of the virus. With this project, we intend, therefore, to quickly meet the national demand for the RT-qPCR standard test and in parallel to develop a rapid test using the RT-LAMP methodology that allows a large number of tests to be carried out to minimize the effects of the outbreak. COVID-19. (AU) With this project, we intend, therefore, to quickly meet the national demand for the RT-qPCR standard test and in parallel to develop a rapid test using the RT-LAMP methodology that allows a large number of tests to be carried out to minimize the effects of the outbreak. COVID-19. (AU) With this project, we intend, therefore, to quickly meet the national demand for the RT-qPCR standard test and in parallel to develop a rapid test using the RT-LAMP methodology that allows a large number of tests to be carried out to minimize the effects of the outbreak. COVID-19.",2020,2022,Cellco Biotec do Brasil,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06371,2020/04797-4,Development and insertion in the market of Electrical Impedance Tomography equipment for the treatment of patients on artificial ventilation due to respiratory failure caused by COVID,"The project aims to develop and place on the market an Electrical Impedance Tomography (TIE) equipment for the treatment of patients on artificial ventilation due to respiratory failure caused by COVID (TIE-COVID). Electric Impedance Tomography is a non-invasive, radiation-free medical equipment used at the bedside, which allows the real-time assessment of regional ventilation distribution, and the identification of phenomena such as asynchrony, pneumothorax, collapse and pulmonary hyperdistention. One of the main problems associated with COVID-19 is the overload of the health system, especially the ICUs, due to the need for ventilatory support for the most critical cases of the disease. While researchers evaluate the use of anti-viral drugs, it is necessary to optimize the ventilatory treatment of the patient, to reduce the length of hospital stay and alleviate the burden imposed on the health system. From the experience of American, Italian and Spanish doctors, we have identified that the handling of the ventilator that COVID-19 requires has often proved to be anti-intuitive. If you only follow the standard protocols for handling the artificial ventilator (such as the ARDSNet table), the treatment, in addition to being ineffective, can cause even greater damage and require longer hospital stays and availability of ventilators. Recent studies indicate that patients with COVID-19 have hypoxemia disproportionate to the radiological and mechanical impairment of the lung; unlike swine flu, respiratory mechanics are good in the early stages of the disease, with lung preservation very well preserved. And here there is a paradox: as the hypoxemia is profound, due to a major failure of hypoxic vasoconstriction, the doctor ends up ""flushing"" and using much higher pressure (PEEP), resulting in hemodynamic impairment and organ failure, leading to a vicious circle that often results in increased length of hospital stay and death. Thus, it is necessary to adjust ventilation individually, minimizing adverse events caused by ventilation, and addressing respiratory failure in a targeted manner. The reduction in complications and the consequent reduction in ventilation time will result in greater availability of ICU beds. To spread the use and increase access to more individualized and effective ventilatory treatment, including for emergency departments in hospitals, this project aims at the development and emergency insertion in the market of an Electric Impedance Tomography (TIE) equipment dedicated for the treatment of patients under artificial ventilation due to respiratory failure caused by COVID (TIE-COVID). The project involves: 1. Development of an algorithm and specific functionality for adjusting the PEEP and treating patients with COVID, to optimize ventilation, so that the patient is released from the ventilator as soon as possible; 2. 40% price reduction in relation to current Timpel equipment, with size reduction, battery inclusion, making the equipment accessible to all ICUs in Brazil; 3. Development of a disposable electrode belt, given the care that must be taken in relation to contamination by coronavirus, cleaning and sterilizing the equipment; 4. Development of remote access to equipment, to allow access to information outside the contaminated environment; 5. Prototyping, verification, validation, 6. ANVISA certification and market insertion; Gross revenue from the project is estimated at R $ 8.6 million as of the first year after launch, reaching R $ 12.5 million in the fifth year.",2020,2021,Timpel,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06372,2020/04986-1,Thermosys - Sistema de identificação de pessoas suspeitas de apresentarem estado febril por meio de imagens nos espectros visível e termal [Gppg;e Translate: Thermosys - System for the identification of people suspected of having a fever through images in the visible and thermal spectra],"In the context of the serious crisis that is plaguing us because of the COVID-19 infection, a system that can select suspected febrile conditions in places of great crowding is imperative. The proposal is for the development of an intelligent imaging system in the visible and thermal spectra that processes the relative data to identify suspected infection. For this, the company is using its experience in multispectral systems and products in its defense portfolio, calibrating them, adapting them and developing the necessary algorithms for this new desired functionality. The system will be formed by cameras in the visible and thermal spectra mounted on a cabinet that can be installed in crowded places. The system will be connected to a platform with algorithms optimized for face detection processing, identification of measurement points and temperature evaluation routines compensating for environmental variables. Prototypes will be made incrementally. Initially with thermal modules of simple acquisition and software operating in laboratory conditions. Thus, adapting the characteristics for the system to operate in the desired function. Subsequently, the modules will be replaced by sensors manufactured by Opto S&D, optimized for the temperature range of interest. In the same way that the first algorithms will be worked in more controlled conditions (distance, temperature and ambient humidity) and then migrating to more diverse conditions in which the system can be used.",2020,-99,Opto Tecnologia Optrônica,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C06373,2020/04921-7,Development of low cost portable ventilators and a Jiga of functional tests and automated calibration,"On 03/20/20, the World Health Organization classified the disease COVID-19 as a pandemic. Without drugs and vaccines approved to fight the disease, the appropriate actions are extremely restricted: Social isolation and investment in mechanical ventilators and PPE. (Ranney, ML et.al. 2020) On 01/20/20 the first case of COVID-19 in the United States was confirmed and in less than 2 months the greatest economic power on the planet announced that it would not have enough equipment to assist patients in critical condition. According to The New York Times, the estimate for the number of patients who will need ventilators could reach one million, where the availability of equipment is between 60 and 160,000 units. Brazil had the confirmation of the first case of the disease and the estimate of incidence and need for hospitalization of infected people is alarming. Our country has a little more than 10 manufacturers of respirators, which together can produce around 1500 devices per month. Brazil has 65 thousand fans (VEJA of 03/27/2020) and if the isolation measures do not flatten the disease transmission curve, the demand may reach 630 thousand units in the worst scenario and 196 thousand in the best (projection based on American curve). In the country each device is sold, on average, for R $ 54,000.00. Countless global actions and initiatives have emerged to provide a quick response to the problem, from open projects for the production of very low-cost fans, even traditional projects made available by manufacturers on the internet for collaboration in emergency manufacturing. Inspired by this response movement to combat COVID-19, SETUP's team of researchers evaluated more than 10 available projects and found two critical aspects: the majority were concerned with developing very low-cost equipment, resulting in products without the necessary robustness to continuous use over the 14 days (average time of mechanical ventilation in the COVID treatment19) and does not meet the minimum requirements for control of vital function performance indicators that should be monitored in a severely ill patient. In addition, consolidated respirator designs in operation today use an old design concept, dedicated and not-so-simple circuits to operate, requiring advanced training of health professionals. The present project consists of constructive and usability improvements for 2 portable ventilator models: a low cost model, containing the minimum of functions to be tested and calibrated in accordance with ABNT IEC 60601 and other applicable standards, and can be used in field hospitals; a complete respirator model with advanced electronic control and simple interface to be used in Intensive Care Units. An automated lung calibration and testing station will also be developed. (AU) that contains the minimum of functions to be tested and calibrated in accordance with ABNT IEC 60601 standards and other applicable standards, and can be used in field hospitals; a complete respirator model with advanced electronic control and simple interface to be used in Intensive Care Units. An automated lung calibration and testing station will also be developed. (AU) that contains the minimum of functions to be tested and calibrated in accordance with ABNT IEC 60601 standards and other applicable standards, and can be used in field hospitals; a complete respirator model with advanced electronic control and simple interface to be used in Intensive Care Units. An automated lung calibration and testing station will also be developed.",2020,2020,Setup Automação e Controle de Processos,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Innovation,,,Brazil,Brazil,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06382,109476,Community approaches for improved health outcomes of urban refugees in Lebanon during the COVID-19 pandemic,"This project will strengthen Lebanon's public health response to COVID-19 and future health emergencies in fragile settings. It will use a multi-pronged approach to meet the needs of refugees and share knowledge to benefit similar needs in Jordan. First, there will be a critical assessment and analysis of the rapid-response actions and policies that have guided Lebanon's management of the pandemic at the national level. This will be complemented by interventions to manage and mitigate risks posed by COVID-19 at the community level. The project will also build capacity for pandemic responses at the local and regional levels. Experiences at the local, national, and global levels will be triangulated to identify good practices and recommend changes. The project will produce guidance to inform a robust national public health response system that benefits both refugee and host communities and that is gender-responsive and inclusive of diverse populations.",2020,-99,American University of Beirut,1007228,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Eastern Mediterranean,Gender,,,Lebanon,Lebanon,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Policy research and interventions | Cross-cutting, +C06383,109478,Effectiveness and scalability of innovative digital health solutions responding to COVID-19 crisis among refugees and vulnerable populations,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leveraging existing local opportunities to strengthen the overall initiative. This project will investigate the effectiveness of developing and scaling up three digital health solutions in strengthening health systems and improving access to care in at-risk populations in Asia, the Middle East, and Africa. The two-year project will use the current COVID-19 pandemic to identify existing gaps in preparedness and early response of health systems. The approach will include quantitative and qualitative methods to study three critical areas related to health emergencies: early detection of illness in at-risk populations; teleconsultation to improve access to care for the hard-to-reach; and mobile applications for best practice guidelines for healthcare workers. The evidence will be communicated through a variety of academic and policy outputs.",2020,-99,Aga Khan Foundation Canada,497040,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Eastern Mediterranean | Europe,Digital Health,,,Canada,Afghanistan | Kenya | Pakistan | Tajikistan | Tanzania,Health Systems Research,Health service delivery, +C06384,109479,"Exploring and learning from evidence, policy, and systems responses to COVID-19 in West and Central Africa","An effective response to COVID-19 requires a complex array of relevant evidence packaged in user-friendly forms to support decision-making about current and future responses. This project will map out existing evidence and its use in informing responses to COVID-19. It will identify sectoral evidence gaps (epidemiological, public health, health system, and health technology capacities, etc.), as well as intervention responses to emerging epidemics and pandemics. It will document, compare, and contrast experiences at national and subnational levels, with a focus on displaced and vulnerable populations across countries and sub-regional contexts. The project will be implemented in six countries in West and Central Africa: Benin, the Democratic Republic of Congo, Ghana, Guinea, Nigeria, and Senegal. To cope with the fast-moving nature of the COVID-19 pandemic, the team is adopting a flexible study approach with iterative analysis over time. The deeper understanding generated by the project will support more detailed work and interventions that benefit displaced and other vulnerable populations. It will have an emphasis on integrating equity and gender considerations, with attention to information and experiences affecting vulnerable populations. The research team will engage with decision-makers to inform evolving decision-making and serve as a strong basis for building resilient health systems. The work will contribute to identifying areas for inclusion in sub-regional observatories and follow-up work in the West and Central Africa region for improved evidence-informed decision-making. The project will build collaborative learning within and across countries through discussions and policy dialogues with key stakeholders to inform appropriate multisectoral responses to COVID-19 and similar health emergencies.",2020,-99,"Ghana Health Service, Prins Leopold Instituut voor Tropische Geneeskunde, Organisation Ouest Africaine de la Santé",949544,Other,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa | Europe,Africa,,,,Ghana | Belgium,Benin | Congo (DRC) | Ghana | Guinea | Nigeria | Senegal,Health Systems Research,Health leadership and governance, +C06385,109469,Health systems strengthening through preparedness in COVID health emergency for refugees and IDPs in the West Bank.,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis both in the short-term and longer-term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leverage local opportunities. This project will generate evidence to understand the effects of the COVID-19 pandemic on refugees and internally-displaced people in the West Bank and the health system's ability to meet their needs. It will also strengthen the health system through incorporating research and health information system strengthening. The methodology for this study will comprise three phases. There will be an initial rapid situation assessments and community engagement to analyze the pandemic response and engage with institutional and policy stakeholders. Next phase is larger scale quantitative and qualitative research activities followed by the translation of research for policy and practice to inform longer term preparedness and resilience of the health system. Throughout these stages, building capacities for research will be carried out, particularly in health system preparedness with regards to health human resources, health information system and community engagement. This project will lead to enhanced knowledge production both for short-term rapid response to COVID-19 as well as a longer-term participatory approach to pandemic preparedness and resilience from a gender and equity perspective for refugee and internally displaced populations.",2020,-99,Birzeit University,523640,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Unspecified,,,,Palestine,,"Policies for public health, disease control & community resilience",Community engagement | Policy research and interventions | Indirect health impacts | Health service delivery | Systemic/environmental components of capacity strengthening, +C06386,109481,"Improving the health and empowerment of migrants, women, and children in Guatemala during the COVID-19 pandemic","This project will study the effects of COVID-19 on the health of refugees and Indigenous populations in parts of rural Guatemala that are experiencing recent waves of refugees migrating into Indigenous communities. This project builds on the existing Network of Community Health Defenders, which monitors healthcare services and policies, and will expand the Network from 30 to 35 rural Indigenous municipalities in Guatemala. In recent years, the Defenders have reported that migrants deported from Mexico or the USA are choosing to stay and live in the Indigenous communities rather than returning to their countries of origin. This is leading to tensions and hostilities within already economically vulnerable communities, and now the COVID-19 pandemic is exacerbating vulnerabilities of women and their families in host communities, as well as among refugees and migrants. To inform the rapid response component of this project, the Defenders will assess health needs, perceptions of COVID-19 risk of infection, and related fears of refugees, migrants, women, and children, and the barriers they experience to access available public services. Based on the findings, and through a community participation approach, the researchers will design policy engagement strategies and specific programs for these vulnerable populations. The strategies and programs will emphasize the empowerment of women. For longer-term preparedness, the project will also analyze how national and social media and other cultural factors are contributing to narratives that maintain and exacerbate gender inequalities, increase fear of the health system among women and other vulnerable populations, and increase social rejection and subsequent health risks of migrants. The project will test positive communication strategies and messages to reduce the fear of COVID-19 among refugees, migrants, women, and communities, support gender equality, and build trust between users of services and healthcare providers - key elements in pandemic preparedness and resilience.",2020,-99,Centro de Estudios para la Equidad y Gobernanza en los Sistemas de Salud (CEGSS),417392,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Rural Population/Setting,Internally Displaced and Migrants | Indigenous People | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Guatemala,Guatemala,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Community engagement | Communication, +C06387,109477,Managing impact of COVID-19 in Rohingya refugee camps with culturally appropriate technological solutions,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leveraging existing local opportunities to strengthen the overall initiative. This project will identify gaps in COVID-19 responses in addressing sexual and reproductive health and maternal and neonatal child health issues among Rohingya refugees and host population women and adolescent girls in Bangladesh. Bangladesh hosts the largest refugee camps in the world, with close to 860,000 stateless Rohingya refugees. The project will use qualitative and quantitative approaches to examine potential health impacts of COVID-19. It will also assess whether deployment of digital interventions (a contact tracing application and a maternal and neonatal child health application) can reduce transmission of COVID-19 and improve sexual and reproductive health and maternal and neonatal child health outcomes respectively. The project will engage government and other key stakeholders to develop and build evidence on the use of these tools. The evidence will inform local policies and the health systems set up in the refugee camps and host communities to combat COVID-19. It will also inform any future health emergencies, enhancing the preparedness and early response aspects of the health system.",2020,-99,"The BRAC University, BRAC, Dimagi, Inc.",558676,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,South-East Asia,South-East Asia,Gender,,,Bangladesh,Bangladesh,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health leadership and governance, +C06388,unknown,Rectifying the effects of COVID-19 on vulnerable populations in West Africa: research-action,"This research team, led by the West African Network of Emerging Leaders in Health Policy and Systems, in collaboration with the Ghana Health Service, uses rapid assessment, case studies, and action research to identify the full impact of COVID-19 on vulnerable populations and to develop innovative strategies to address their priority needs across West Africa.",2020,-99,N/A,,Human Populations,White,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C06389,109480,Strengthening access to sexual and reproductive health services for internally displaced people during COVID-19 in Burkina Faso [French title: Renforcer l'accès aux services de santé sexuelle et reproductive et aux droits connexes chez les personnes déplacées internes en période de pandémie de la COVID-19 au Burkina Faso : Projet SSRD-COVID],"Refugee and displaced populations, and the vulnerable communities with whom they share space, are at high risk for acquiring COVID-19 because their living conditions make it impossible to practice physical distancing and isolation or to access quality healthcare. Refugee women are particularly vulnerable because their limited access to sexual and reproductive health services and products is further interrupted and their duties as caretakers, especially in under-resourced refugee settings, are increased. This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and the longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations. It will also leverage existing local opportunities to strengthen the overall initiative. This project will assess and respond to the needs of an internally displaced population in the fragile context of Burkina Faso, where growing conflict and terrorism may turn into a chronic development crisis. It focuses on increasing access to sexual and reproductive health services and related rights of internally displaced adolescents and women in the context of COVID-19. Firstly, it will identify the needs, constraints, and facilitating factors for using such services before developing and implementing an intervention to improve access to and awareness of sexual and reproductive health services and rights. The project will document the results and disseminate them as lessons learned to strengthen current and future responses to similar health crises.",2020,-99,Université Ouaga 1 Professeur Joseph KI-ZERBO,442320,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Gender,,,Burkina Faso,Burkina Faso,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery, +C06391,109492,The impact of COVID-19 on inclusive development and democratic governance: rapid and post-pandemic assessment in the Mekong subregion,"This project aims to support inclusive, coordinated, and gender-sensitive responses to the COVID-19 pandemic in Cambodia, Laos, Myanmar, and Vietnam. It will assess the socioeconomic impacts of the COVID-19 pandemic and the effectiveness of responses. The project will explore the current conditions of the economy, firms, and workers, the policy responses intended to support them, the mitigation strategies they have employed, and the level of coordination across various actors that is critical to a strong and inclusive recovery. In close coordination with local governments and organizations, the project will identify gender-sensitive policies and good practices from the macro to micro level that will support the recovery process and improve resilience among vulnerable women workers and micro, small, and medium enterprises. It will facilitate policy dialogue and coordination among researchers, policymakers, private sector actors, civil society, and women's organizations in the response and recovery phases. Finally, it will enhance the capacity of the implementing consortium members to create partnerships, cooperation, and learning at the regional level with international dialogues, comparative research activities, and by engaging regional organizations.",2020,-99,The Cambodia Development Resource Institute,1099875,Human Populations | Other,Unspecified,Unspecified,Unspecified,Women | Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,South-East Asia | Western Pacific,Gender,,,Cambodia,Cambodia | Lao People's Democratic Republic | Myanmar | Viet Nam,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C06392,109496,"Shaping the macro-economy in response to COVID-19: a responsible economic stimulus, a stable financial sector, and a revival in exports","This project aims to contribute to the knowledge on macroeconomic policies that are key for responses to the COVID-19 pandemic in low-income countries. The impacts of the pandemic on the economies of these countries is significant, contributing to growing poverty and hunger. There is an urgent need for credible data, analysis, and advice for the economic policies and the fiscal and monetary measures required to mitigate the impacts and promote an inclusive and sustainable recovery. The project will be led by the Overseas Development Institute in the UK, in collaboration with think tanks in Bangladesh, Sri Lanka, Kenya, Tanzania, and Peru, and the network Southern Voice. This partnership will develop credible evidence that can support national and international policies in response to the pandemic, focusing on macroeconomic performance, growth scenarios, and macroeconomic policy options, with a focus on gender equality and climate change outcomes.",2020,-99,Overseas Development Institute,350550,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Africa | Americas | South-East Asia,,,,United Kingdom,Bangladesh | Kenya | Peru | Sri Lanka | Tanzania,"Secondary impacts of disease, response & control measures",Economic impacts, +C06393,109528,The impact of the COVID-19 pandemic on livelihoods in Africa,"This project will undertake research on the impacts of the COVID-19 pandemic on the livelihoods of vulnerable populations in Ethiopia, Kenya, Nigeria, Senegal, South Africa, and Zambia. The goal is to inform evidence-based decision-making in the policy responses to the COVID-19 pandemic in these countries. The project will evaluate the impact of the pandemic on key macroeconomic indicators and on issues such as food security, malnutrition, and hunger. It will also examine gender-specific socio-economic impacts. The project aims to build the capacity of researchers and institutions for longer-term, sustainable policy changes that address root causes of the pandemic's unequal impact, including gender inequality. It also aims to build a network of stakeholders (individuals and policy, research, and practice institutions) that can continue to track the pandemic's impacts and design and advocate for practical solutions in the post-COVID era.",2020,-99,African Economic Research Consortium/Consortium pour la recherche économique en Afrique,918450,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Gender,,,Kenya,Ethiopia | Kenya | Nigeria | Senegal | Zambia,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C06394,109529,Mitigating socio-economic impacts of COVID-19 and promoting post-pandemic resilience in Uganda,"This project will examine the policies, measures, and strategies to mitigate the socio-economic impacts of COVID-19 on households and small and medium-sized enterprises. It will also look at the interventions required to re-activate resilience of the Ugandan economy post-COVID-19. Using quantitative and qualitative methods, it will examine how the pandemic has affected business operations, the coping mechanisms businesses have adopted, and the support they require. The study will generate country-specific data and evidence-based research on the immediate, short-, medium-, and long-term impacts of the pandemic, mitigation measures, and policy responses. The findings will feed directly into ongoing policy processes to find solutions to the problems caused by the pandemic in Uganda.",2020,-99,Economic Policy Research Centre,486675,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Uganda,Uganda,"Secondary impacts of disease, response & control measures",Economic impacts, +C06395,109532,COVID-19 macroeconomic policy response in Africa,"Many developing countries do not have sufficient financial, monetary, and social instruments for the necessary immediate and long-term responses to the COVID-19 pandemic. This project aims to inform policy responses in Benin, Nigeria, Senegal, South Africa, Tanzania, and Uganda. It will generate evidence to support policymakers, specifically finance ministries, to promote equitable socioeconomic and sustainable environmental policies and interventions in the short and long- term. The project will also support peer learning and capacity building among targeted policymakers and policy think tanks for strong pandemic responses on fiscal and monetary measures, financing and programming options to support vulnerable groups, and rebuilding economies to be climate-resilient, sustainable, and inclusive.",2020,-99,The South African Institute of International Affairs,1115325,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,South Africa,Benin | Nigeria | Senegal | Tanzania | Uganda,"Secondary impacts of disease, response & control measures",Economic impacts, +C06396,109486,Informal workers and COVID-19: evidence-based responses to the crisis at the base of the economic pyramid,"This project focuses on the impact of the COVID-19 pandemic and associated lockdowns on the livelihoods and health of poor workers, especially women, in the informal economy. Over 90% of workers in developing countries are informally employed, with higher rates of informal employment for women. While the impact of the pandemic has been catastrophic for these workers, evidence on how they are affected is not yet available to inform a policy response, especially during the recovery phase. The informal economy is so diverse that nuanced information is required about how the crisis exacerbates existing vulnerabilities for different groups of informal workers and about how different groups of informal workers contribute as essential frontline workers. This project will do so using a mixed-methods longitudinal study that includes a large-scale survey of informal workers spanning over 10 cities across eight countries, with a focus on four groups that predominantly employ women: domestic workers, home-based workers, street vendors, and waste pickers. The findings will inform policies and actions needed to address the impacts of the pandemic. They will also highlight how existing responses are affecting informal workers in ways that deepen or reduce inequalities. Ultimately, this project will contribute novel and contextually grounded evidence to ensure a fundamental rethink of the underlying injustices and inequities that exacerbate the negative impact of the pandemic on informal workers, with a focus on women.",2020,-99,Women in Informal Employment: Globalizing and Organizing (WIEGO) Limited,706125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Africa | Americas | South-East Asia,,,,United Kingdom,Ghana | India | Mexico | Peru | Senegal | Tanzania | Thailand,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C06397,109487,"Economies beyond emergencies: assessing impacts of COVID-19 policy responses on informal workers in India, Kenya, and Uganda","The COVID-19 pandemic has wrought a global socio-economic crisis, with profound implications for the wellbeing of individuals, households, and communities. It has further deepened existing social inequalities and heightened risks for gender-based violence and violation of sexual and reproductive health and rights among marginalized groups. The disruption in livelihoods and protective networks has undermined the bargaining power of women, exposing them to higher risk of abuse and exploitation in domestic and public spaces and in the workplace. This further sets the stage for the increased occurrence of harmful traditional practices that are anchored in gender norms, such as female genital mutilation, early and forced child marriages, and child labour. This project will undertake research to inform gender-responsive, accountable, and democratic policies and strategies that ensure vulnerable populations affected by COVID-19, such as female workers in informal urban economies, can recover and rebuild their lives and livelihoods. Research in three urban settings in India, Kenya, and Uganda will generate data on the impact of the COVID-19 response on women workers in the informal economy. This will provide an understanding of how gender norms, pathways to economic empowerment, and the gendered impacts of violence and access to essential health services can inform policy that is responsive to the specific needs of women workers in these informal economies.",2020,-99,International Center for Research on Women,675000,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Other | Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | South-East Asia,Gender,,,United States of America,India | Kenya | Uganda,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts, +C06398,109490,Strengthening public policies for decent work in Francophone Africa in the context of the COVID-19 pandemic,"The project seeks to analyze the impact of the COVID-19 pandemic on small informal businesses in Benin, Cameroon, Morocco, and Senegal. It will explore policy options for targeted support to those businesses in a way that helps contain the spread of COVID-19 and similar pandemics in the future. It will also seek to identify the best options for building the long-term resilience of vulnerable population groups involved in small informal businesses. Using mixed methodologies, the research team will conduct multidisciplinary analyses integrating gender considerations to better understand the specific challenges facing women and young people. It will then propose appropriate strategies for tailored support. The findings will help to inform the deliberations of the presidential COVID-19 response unit in Senegal, the bureau for economic analysis at the Presidency of Benin, and the COVID-19 national response unit in Cameroon.",2020,-99,Université Cheikh Anta Diop,927300,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Gender,,,Senegal,Benin | Cameroon | Morocco | Senegal,"Secondary impacts of disease, response & control measures",Economic impacts, +C06399,109494,Impact of COVID-19 on family farming and food security in Latin America: evidence-based public policy responses,"The COVID-19 pandemic is threatening the livelihoods and food security of millions of people. Family farming provides a significant share of the food supply and has an important role in the transition toward sustainable agri-food systems and the fight against a possible food crisis. This sector is facing multiple challenges that are exacerbated under the current pandemic. This project, implemented in Chile, Colombia, Ecuador, Guatemala, and Mexico, will generate evidence and promote changes to agri-food systems in the aftermath of the pandemic. It will contribute to mitigating the impact on food security and consumption patterns of the most vulnerable, with an emphasis on women. It will promote small- and medium-scale farming, in addition to agri-food systems that are more sustainable, gender-sensitive, inclusive, and resilient to shocks such as the COVID-19 pandemic.",2020,-99,Corporación de Derecho Privado Rimisp - Centro Latinoamericano para el Desarrollo Rural (Rimisp),1041525,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Colombia | Ecuador | Guatemala | Mexico,Colombia | Ecuador | Guatemala | Mexico,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C06400,109495,"Addressing the socioeconomic impacts of COVID-19 with a gender lens: food systems, labour markets, and social protection in Latin America","The COVID-19 pandemic and confinement are causing severe disruption to labour markets and food security in Latin America, exacerbating structural labour market challenges such as informality, inequality, and low productivity. Millions of workers are left unprotected, highlighting the need to strengthen social protection systems. The impact on the food system is exacerbating inefficiencies and inequalities, putting the livelihoods of small producers and access to healthy food for poor consumers at risk. So far, most Latin American governments have failed to enact policy measures to tackle these problems. This project will support evidence, technical assistance, and a pilot of policy responses addressing food systems, labour market challenges, and social protection that emphasize gender and diversity. It will propose timely and cost-effective policy responses to foster food security and more efficient and inclusive traditional food markets; support the design and piloting of innovative social protection programs to reach informal workers; and inform temporary employment policies for Latin America to reduce the socio-economic impacts of the pandemic and to promote a more equitable and sustainable recovery. The project will also have global reach and foster Southern researchers' visibility and leadership, with at least 15 scholars from the region engaging on global policy dialogues on COVID-19 responses. The project will be implemented in Peru, Ecuador, and two additional Latin American countries that will be selected according to the impact of the pandemic, potential for policy impact, and research capacities.",2020,-99,Group of Analysis for Development (GRADE),1111275,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,Gender,,,Peru,Ecuador | Peru,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts, +C06401,109498,Providing timely evidence to facilitate socio-economic recovery from the COVID-19 pandemic in Rwanda,"This project aims to facilitate evidence-based decision-making to provide appropriate socio-economic responses to the COVID-19 outbreak in Rwanda. Over a period of three years, the project will collect data on a set of 10,000 vulnerable households and 4,500 micro-, small-, and medium-sized businesses. The goal is to gather instantaneous and ready-to-use information on the socio-economic and labour market impacts of COVID-19. The information will be disseminated to decision-makers and other stakeholders and will provide the basis for the development of policy options for the Government of Rwanda to respond to challenges faced by businesses and households. The project will also reinforce the capacities of researchers in Rwanda.",2020,-99,Institute of Policy Analysis and Research (IPAR-Rwanda),764475,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Rwanda,Rwanda,"Secondary impacts of disease, response & control measures",Economic impacts, +C06402,109499,"Supporting small and medium enterprises, food security, and evolving social protection mechanisms to deal with COVID-19 in Pakistan","To prevent the spread of COVID-19 infections, Pakistan enforced a strict lockdown and quarantine system. This system, however, is negatively affecting many sectors of the economy, with a disproportionately high impact on the livelihoods of the most vulnerable. Among the most affected sectors are food production and disrupted food supply chains, where small and medium enterprises are facing massive layoffs or closures. This project will provide evidence-based advice to the government of Pakistan to respond to the crisis, guide rapid policy responses, and develop measures to build resilience for the post-COVID period. It will generate and feed information to a national food security dashboard to facilitate the transportation of food commodities from surplus districts to deficit districts, contributing to food security. The project will also map formal and informal small and medium enterprises (SMEs) in the country and provide evidence on the effectiveness of the current stimulus package to strengthen national SME policy. In addition, given that existing social safety nets are insufficient to support the 60% of Pakistan's labour force working in informal undocumented sectors of the economy, there is an urgent need for an in-depth analysis of existing social protection mechanisms to devise a roadmap for a universal social protection regime in Pakistan. The project will help fill information and action gaps and serve as a bridge between policymakers and the needs of millions of daily wage earners in rural and urban areas, leading to positive impacts on the livelihoods of millions of vulnerable Pakistanis.",2020,-99,Sustainable Development Policy Institute,532125,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Eastern Mediterranean,Gender,,,Pakistan,Pakistan,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C06403,109527,Simulations and field experiments of policy responses and interventions to promote inclusive adaptation to and recovery from the COVID-19 crisis,"This project aims to assess the impacts of the COVID-19 pandemic on national economies and determine the effectiveness of current and potential policy responses in 11 developing countries around the world. It will analyze factors such as sectoral/total production, employment, trade, etc. on national economies, and particularly on household poverty/inequality. It will simulate the impacts of socio-economic policy responses during the lockdown, reopening, and recovery phases and develop a policy simulation model that local researchers and government officials may use to address other policy challenges during and after the current project, and to support governments in the design of effective policy responses. It will also identify general lessons to guide policies in other developing countries.",2020,-99,Partnership for Economic Policy (PEP),902100,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa | Americas | Eastern Mediterranean | Western Pacific,,,,Kenya,Argentina | Benin | Ecuador | Ethiopia | Ghana | Cote d'Ivoire | Kenya | Nigeria | Pakistan | Viet Nam | Zimbabwe,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts, +C06404,109530,"Impacts of public policies related to COVID-19 pandemic on the informal sector, young people, and women","This project will document and analyze the impact of the COVID-19 pandemic on vulnerable groups in Burkina Faso, Cameroon, Côte d'Ivoire, and Senegal. Using qualitative and quantitative techniques, the research team will analyze changes in activities, income, consumption, and well-being, including indicators such as domestic violence and the level of confidence in the future on the part of young people, women, and people working in the informal sector. The team will collect up-to-date and robust data on the impact of the COVID-19 outbreak on vulnerable households and micro-, small-, and medium-sized enterprises; disseminate this information in a clear and accessible way to decision-makers and other stakeholders; provide policy response proposals to the COVID-19 outbreak to improve the conditions of households and businesses; and reinforce capacities of researchers in Rwanda.",2020,-99,Centre Ivoirien de Recherches Économiques et Sociales (CIRES),908550,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Cote d'Ivoire,Burkina Faso | Cameroon | Cote d'Ivoire | Senegal | Rwanda,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts | Economic impacts, +C06405,109488,A new digital deal for an inclusive post-COVID-19 social compact: developing digital strategies for social and economic reconstruction,"For many people around the world, digital technologies have enabled the continuation of work, education, and communication during the COVID-19 pandemic. But for half the world's population who cannot connect to the internet, the pandemic has put a renewed spotlight on the uneven access to and distribution of digital technologies globally. This enduring digital divide undermines governments' abilities to harness technologies for the efficient and safe delivery of necessary services online, and that in turn means education, commerce, and relief support is not accessible for many who need it most. This project will study the linkages between the informal economy and the digital transformation of governance. Among the issues under examination are the potential to ""formalize"" small firms and thus increase the tax base that funds social protection; the impact of digital services during lockdown and eventual recovery; the factors that undermine digital access; and the role of democratic governance and accountability. The project aims to inform policy debates on the role of digitalization in the management of disasters and pandemics, and the economic and social reconstruction of emerging economies. It will provide immediate signals to policymakers on the strengths and deficiencies of current response strategies and help create conditions for economic recovery through improved information flows and efficiencies associated with digitization. The project will involve six countries: Colombia, India, Nigeria, Peru, South Africa, and Sri Lanka, and will generate comparisons with other countries in those regions.",2020,-99,Research ICT Africa,1251075,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa | Americas | South-East Asia,,,,South Africa,Colombia | India | Nigeria | Peru | Sri Lanka,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C06406,109489,"Socio-economic impact of COVID-19 on African economies, social cohesion, and governance: evidence from Benin, Burkina Faso, and South Africa","This collaborative project will contribute to policies and strategies to address the immediate and longer-term effects of the COVID-19 pandemic on economies, social cohesion, and governance in Benin, Burkina Faso, and South Africa. The multidisciplinary and multi-country team of researchers, composed of both men and women, will investigate the negative income shock and state regulations resulting from the pandemic and their corresponding effects on social cohesion, governance, and violence (including violent extremism) in Africa. They will employ mixed methods and a comparative approach across contexts, conduct experiments, and analyze secondary data sources, incorporating a strong gender analysis throughout. The study findings will be positioned for use by policymakers, practitioners, and civil society actors to inform the design and implementation of effective responses to the various effects of the COVID-19 pandemic in Benin, Burkina Faso, South Africa and beyond. The project will contribute to enhancing collaboration between researchers in Africa and strengthen their contribution to the development of effective and rapid responses to the social and economic effects of the pandemic in Africa.",2020,-99,Université d'Abomey-Calavi,909000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Gender,,,Benin,Benin | Burkina Faso,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts, +C06407,109491,Promoting resilience in COVID-19 MENA: building inclusive and effective social protection and safety nets,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis both in the short term and in the longer term. The initiative will support research on building resilience and preparedness to serve the needs of refugees and other populations on the move by promoting intersectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations. It will leverage existing local opportunities to strengthen the overall initiative. This project will generate evidence on the effects of the COVID-19 pandemic on refugees and internally displaced people in the West Bank and the health system's ability to meet their needs. It will also strengthen the health system through incorporating research and health information system improvements. Activities will include initial rapid situation assessments and community engagement to analyze the pandemic response and engage with institutional and policy stakeholders. This will be followed by larger scale quantitative and qualitative research activities. Finally, the research will be presented in an accessible format for policymakers and practitioners to inform long-term health system preparedness and resilience. The project will also support capacity building for research in health system preparedness with regards to human resources, information systems, and community engagement. This will lead to enhanced knowledge production, both for short-term rapid response to COVID-19, and for a long-term participatory approach to pandemic preparedness and resilience from a gender and equity perspective for refugee and internally displaced populations.",2020,-99,Arab Reform Initiative (ARI),1124400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Africa | Eastern Mediterranean,,,,France,Egypt | Jordan | Lebanon | Tunisia,"Health Systems Research | Policies for public health, disease control & community resilience",Health service delivery | Health leadership and governance | Community engagement, +C06408,109493,"Bridging communities in Cox's Bazar: mitigating risks and promoting gender, governance and localization of humanitarian responses in COVID-19 era","This project aims to assist policymaking and civic engagement in the context of the COVID-19 pandemic, both within refugee communities and between host and refugee communities in Bangladesh. A rapid and longitudinal research study on the safety and security concerns of vulnerable refugee groups will provide evidence that can build tolerance and peace-building initiatives and enhance the psychosocial well-being of refugees and host communities. The study will emphasize collaboration between refugee communities, host communities, humanitarian actors, and governments. The aim is to co-create new approaches to promote greater localization of humanitarian interventions and use a gender-transformative lens in relation to acutely vulnerable groups. Research findings and recommendations will be shared through meetings and dialogues with government representatives, volunteers, community-based organizations, local non-governmental organizations, and UN agencies using online and offline platforms.",2020,-99,The BRAC University,930225,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,South-East Asia,Africa | Americas | South-East Asia,,,,Bangladesh,Bangladesh | Kenya | Peru | Sri Lanka | Tanzania,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts, +C06409,109497,Addressing COVID-19-related vulnerabilities for migrant returnees in Central America's Northern Triangle,"Central America's Northern Triangle (Guatemala, Honduras, and El Salvador) is well known for its high rates of violence and poverty, correlated with high rates of migration under vulnerable conditions. Recent shifts in migration policy, particularly in the USA, have contributed to a mass return of Central Americans. The COVID-19 crisis has further aggravated the invisibility and vulnerability of these returnees (particularly youth and women) and has exposed their dire economic and security conditions amidst the pandemic. These include growing rates of gender-based violence, difficulties accessing economic opportunities, and poor access to basic services and information, both in quarantine centres and upon their reintegration into host communities. This project seeks to promote efficient policy responses by identifying and addressing the labour reintegration and gender-based violence challenges and experiences faced by migrant returnees in the Northern Triangle with an emphasis on female and youth returnees. It will also examine the different vulnerabilities that COVID-19 imposes in these contexts. A diagnosis of returnees' economic and security vulnerabilities will be conducted in six communities across the Northern Triangle, involving surveys and interviews with migrants, local organizations, and public officials. It will evaluate the most effective short and medium-term responses required to meet the economic and human security needs of these returnees. Engagement efforts to promote uptake will include discussion forums and information campaigns.",2020,-99,Asociación de Investigación y Estudios Sociales/Association for Research and Social Studies,937500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,Gender,,,Guatemala,El Salvador | Guatemala | Honduras,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts | Economic impacts, +C06410,109500,"Social engagement, citizen agency, and governance: toward a new democratic consensus in post-pandemic Latin America","This project seeks to understand how governments and citizen groups have organized responses to the COVID-19 crisis, and the social, political, and institutional dynamics that shaped responses in Argentina, Bolivia, Chile, Colombia, Guatemala, and Mexico. It will assess how the pandemic and the responses to the crisis have affected the social contract between citizens and the state as well as the social cohesion among citizens. The project places a special emphasis on how the pandemic has affected the ability of women and vulnerable populations to shape strategies in the context of the already high poverty rates of women, Indigenous people, and those of African descent. The groups most vulnerable to the economic and health impacts of COVID-19 are also the most likely to be politically marginalized during the crisis. The project's aim is to support improvements in the policies and practices of engagement with vulnerable groups for both civil society organizations and government agencies. It will identify both failings and innovations in governance by examining practices of citizen engagement, distinct political arrangements, approaches to policy co-creation, and the use of technology as a tool for connecting state agencies and policymakers to the public. It will highlight models of leadership and governance in response to the crisis. It aims to strengthen civil society-led initiatives, incorporate new innovations, and help mobilize the agency of vulnerable groups. Finally, the activities will inform discussions about how to revitalize democratic politics amid declining public trust in traditional political institutions.",2020,-99,"Asuntos del Sur Asociacion Civil, ASOCIACIÓN CIVIL DIÁLOGOS, Icesi University",1004100,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Argentina | Guatemala | Colombia,Argentina | Bolivia | Colombia | Guatemala | Mexico,"Policies for public health, disease control & community resilience",Community engagement, +C06411,109531,"COVID-19 and the youth question in Africa: impact, response, and protection measures in the IGAD region (COYOQA)","This project will not only analyze how young people are affected by COVID-19, it will examine how they can be key actors in the response, mitigation, and evaluation efforts of pandemic policies and actions. It aims to ensure that emerging policies are responsive and promote inclusive governance and accountability by seeking to investigate how social accountability can be factored into COVID-19 responses in three member states (Ethiopia, Kenya, and Uganda) of the Intergovernmental Authority on Development (IGAD), a regional bloc of eight member states in the Horn of Africa. The project focuses on enabling youth-driven documentation of reliable, contextually grounded local data analysis and rapid feedback to local and national authorities and to communities through the development of a citizen-led performance monitoring framework. The focus is on informing policies and decision-making to mitigate the social and economic impacts of COVID-19 and prevent its re-emergence. This project will support youth-led policy influence and encourage the use of research evidence to improve community responses to impacts of COVID-19 and build resilience. By providing rapid support to ongoing work, innovating new ways of learning and sharing, and enhancing capacities to inform current and future policy and practice solutions, the project aims to strengthen the overall governance of the COVID-19 crisis and its aftermath. Ultimately, the project seeks to contribute towards strengthening the social contract and fostering democratic peace in pandemic and post-crisis responses.",2020,-99,Organization for Social Science Research in Eastern and Southern Africa (OSSREA),761625,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Innovation,,,Ethiopia,Ethiopia | Kenya | Uganda,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts, +C06412,unknown,Research on the development of immediate clinical testing systems for SARS-CoV-2,,2020,2020,"Faculty of Engineering , University of Toyama",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06413,unknown,Development of BEF peptides for visualization virus in live cell,,2020,2020,"RIKEN Cluster for Pioneering Research Nano Medical Engineering laboratory, RIKEN",,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06414,unknown,"Highly customizable, rapid and simple detection of pathogen-related RNA",,2020,2020,"School of Life Science and Technology , Tokyo Institute of Technology",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06415,unknown,Precision and portable diagnostics for viruses with new genome editing technology,,2020,2020,"The Institute of Medical Science, The University of Tokyo",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06416,unknown,Development of a recombinant vaccine against SARS-CoV-2 using a cynomolgus macaque model,,2020,2020,"Department of Pathology, Shiga University of Medical Science",,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06417,unknown,Development of vaccines against COVID-19,,2020,2020,"Center for Medical Innovation , Nagasaki University",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06418,unknown,Development of SARS-CoV-2 nanoparticle vaccine inducing mucosal immune responses,,2020,2020,"Department of Biochemistry and Molecular Biology, Hirosaki University",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06419,unknown,Development of sublingual vaccine to induce the defined epitope-specific IgA able to protect infection of the novel corona virus.,,2020,2020,"Innovative Clinical Research, Center of Hospital Kanazawa University",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06420,unknown,Investigation of the biological principle of the pathogenicity and cross-species transmission of emerging virus infections including SARS-CoV-2,,2020,2020,"Institute of Medical Science , University of Tokyo",,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06421,unknown,Research on development of predictive markers for COVID-19 prognosis,,2020,2020,"Genome Medical Sciences Project , National Center for Global Health and Medicine",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C06422,unknown,Patient Stratification for Optimizing Resource Distribution and Outcome,,2020,2020,"Department of Medicine, Yokohama City University",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C06423,unknown,Antibody response against SARS-CoV-2 infection and serosurveillance,,2020,2020,"Institute of Medical Science, University of Tokyo",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +C06424,unknown,Research on the diagnosis and treatment of severe respiratory infections caused by viruses,,2020,2020,"Pediatrics, Aichi Medical University",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Other,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06426,unknown,Development of methods of prevention or treatment for severe pneumonia caused by SARS-CoV2 infection,,2020,2020,"Research Institute for Microbial Disease, Osaka University",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2020 +C06427,unknown,Platform development for finding optimal antiviral treatment based on non-specific virus infection dynamics,,2020,2020,"Department of Biology, Kyushu University",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",,2020 +C06428,unknown,"Development of artificial nucleic acid aptamer for diagnosis, prevention and treatment of COVID-19",,2020,2020,"Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +C06429,unknown,"Development of rapid, point-of-care diagnostic tool applicable for emerging infectious diseases without a need of specific device nor technique",,2020,2020,"Faculty of Medical Technology, Teikyo University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06430,unknown,Development of a triage system for the severity of COVID19 pneumonia using artificial intelligence,,2020,2020,"Department of hematology and oncology, The University of Tokyo Hospital",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Japan,Japan,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06431,unknown,Research and development of cloud-based lesion quantification system for emerging and re-emerging infectious diseases such as COVID-19 using interstitial pneumonia quantification technology.,,2020,2020,"Department of Respiratory Medicine, Kyoto University",,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,Digital Health,,,Japan,Japan,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06432,unknown,"Randomized, Embedded, Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP) for COVID-19 response",,2020,2020,"Department of Emergency and Critical Care Medicine, Department of Emergency and Critical Care Medicine",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase),2020 +C06433,unknown,Study of the screening of the donor patients for the plasma transfusion therapy by measuring the neutralization antibody against COVID-19.,,2020,2020,"Department of Intractable Diseases, National Center for Global Health and Medicine",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C06434,unknown,"Validation of anti-SARS-CoV2 antibody detection methods and application to the preventive medicine, using the biospecimen and data stored in population- and hospital- based biobanks",,2020,2020,"Tohoku Medical Megabank Organization,",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Immunity | Disease pathogenesis,2020 +C06435,unknown,Development of therapeutic vaccine-like cell-based drug available to various emerging infectious diseases,,2020,2020,"Graduate School of Pharmaceutical Sciences, Kyushu University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06436,unknown,Therapeutic small molecule drug development program for novel coronavirus disease (COVID-19),,2020,2020,"Research Planning Development , Shionogi & Co., Ltd.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06437,unknown,Development program for therapeutic neutralizing antibodies against the Novel Coronavirus (SARS-CoV-2),,2020,2020,"Pharma & Supplemental Nutrition Solutions Vehicle, KANEKA CORPORATION",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06438,unknown,Phase 1 Clinical Trial Using Allogenic Umbilical Cord-derived Mesenchymal Stromal Cells in Severe COVID-19-related ARDS,,2020,2020,"Department of Manufacturing Technology, Human Life CORD Inc",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 0 clinical trial,2020 +C06439,unknown,Conducting Phase II/III study of rhGM-CSF in patients with novel coronavirus infection (COVID-19).,,2020,2020,"Research & Development, Nobelpharma Co Ltd.",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 0 clinical trial | Phase 1 clinical trial,2020 +C06440,unknown,Development of therapeutic drugs for preventing the progression to severe COVID-19,,2020,2020,"Tsukuba Research Laboratories, Eisai Co.,Ltd.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06441,unknown,"Japanese, multicenter, phase II trial of combination therapy with favipiravir and corticosteroids for coronavirus disease (COVID-19) patients with mild respiratory failure: J-CRITICAL trial",,2020,2020,"Department of Respiratory Medicine , Nagoya University",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C06442,unknown,Developing main protease inhibitor for COVID-19 treatment,,2020,2020,"Research Institute, National Center for Global Health and Medicine",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06443,unknown,"Development of COVID-19 therapeutic agent based on the Ōmura natural compound, Avermectin",,2020,2020,"?mura Satoshi Memorial Institute, Kitasato University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06444,unknown,COVID-19 Kitasato Project; Investigator-initiated clinical trial of ivermectin for additional indication to COVID-19,,2020,2020,"Department of Rheumatology and Infectious Diseases, Kitasato University",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C06445,unknown,Establishing convalescent plasma treatment for COVID-19,,2020,2020,National Center for Global Health and Medicine,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06446,unknown,Treatment strategy with combination therapy for novel coronavirus disease (COVID-19),,2020,2020,"Dep. of Refractory Viral Infection, Research Institute , International University of Health and Welfare, School of Medicine",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2020 +C06447,unknown,Developing COVD-19 specific globulin agents by identifying epitopes of neutralizing antibodies in convalescent patients.,,2020,2020,"Department of Intractable Diseases, National Center for Global Healthand Medicine",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C06448,unknown,Development and safety assessment of combination drugs and nucleolus-related novel drugs for COVID-19,,2020,2020,"Research Institute for Microbial Diseases, Osaka University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06449,unknown,Development of a therapeutic antibody cocktail for COVID-19,,2020,2020,"Graduate School of Medicine, Tokushima University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06450,unknown,Immunoregulatory drug development to prevent recurrent pandemic COVID-19,,2020,2020,"Department of Immunology and Genomic Medicine, Kyoto University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06451,unknown,A phase II investigator-initiated study to evaluate the efficacy and safety of PAI-1 inhibitor TM5614 in patients with SARS-CoV-2 pneumonia,,2020,2020,"Graduate School of Medicine, Tohoku Universi",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C06452,unknown,Development of anti-COVID-19 therapy to suppress severe pneumonia by combination using adenovirus vector with ultra-multi guide RNA expression system and protease inhibitors.,,2020,2020,"Department of Infectious Diseases and Host Defense, Gunma University",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2020 +C06453,unknown,Development of novel immunotherapy against COVID-19 using alpaca VHH technology,,2020,2020,"Department of Hematology & Oncology , Kyoto University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06454,unknown,Development of universal T cell therapy for novel coronavirus disease (COVID-19),,2020,2020,"Institute for Frontier Life and Medical Sciences, Kyoto University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06455,unknown,Therapeutic drug development program to suppress pandemic infection of COVID-19.,,2020,2020,"Department of Anatomy and Developmental Biology, Kyoto University",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",,2020 +C06456,unknown,Establishment of human monoclonal antibodies that neutralize a novel coronavirus (SARS-CoV-2),,2020,2020,"Joint research Center for Human retrovirus Infection, Kumamoto University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06457,unknown,Establishment of the antibody therapy against novel coronavirus disease (COVID-19),,2020,2020,"Institute of Medical Science, University of Tokyo",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06458,unknown,Development of novel amodiaquine derivatives effective in the treatment of novel coronavirus infection,,2020,2020,"Joint Research Center for Huma Retrovirus Infection, Kagoshima University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06459,unknown,Novel anti-viral strategy against SARS-CoV-2 by RdRP inhibitors,,2020,2020,"Division of Cancer Stem Cell, National Cancer Center",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06460,unknown,Therapeutic drug development for severe pneumonia requiring mechanical ventilation caused by COVID-19 - Phase 2a trial,,2020,2020,"Department of Internal Medicine, Miyazaki University",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C06461,unknown,Development of drug for the therapy of severe COVID-19,,2020,2020,"School of Medicine, Shinshu University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06462,unknown,Development of a novel crude drug extract preparation which prevents the exacerbation of COVID-19 patients in the early stage of infection,,2020,2020,"Oriental Medicine Research Center, Kitasato University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06463,unknown,Intestinal ventilation-based therapeutics development for COVID-19 related severe respiratory complications,,2020,2020,"Institute of Research, Tokyo Medical and Dental University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06464,unknown,"Development of new antiviral drugs against emerging and re-emerging infectious diseases, includingnovel coronavirus disease (COVID-19)",,2020,2020,"Department of safety research on blood and biologics, National institute of infectious diseases",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06465,unknown,Development of in vivo tissue regeneration-inducing medicine for patients with COVID-19 pneumonia,,2020,2020,"Department of Pharmacological Research, StemRIM Inc.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06466,unknown,Development of therapeutic drug for COVID-19 associated severe pneumonia.,,2020,2020,Himuka AM Pharma Corp.,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06467,unknown,Development of a novel COVID-19 therapeutic drug for asymptomatic and mild patients by using inhaled,,2020,2020,"R&D Department, SENTAN Pharma Inc.",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",,2020 +C06468,unknown,Development of novel complement targeting antibody therapy against fatal COVID-19 complications.,,2020,2020,"T-CiRA Discovery, Takeda pharmaceutical company limited.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06469,unknown,Therapeutic drug development program based on targeted protein degradation for novel coronavirus disease (COVID-19),,2020,2020,"Medicinal Chemistry Research Laboratories, Department of New Drug Research Division, Otsuka Pharmaceutical Co., Ltd.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06470,unknown,Development of COVID-19 treatment based on the Cryo-EM Single Particle structur alanalysis of SARS-CoV-2 RdRP-DNA Aptamer complex,,2020,2020,"Research and Development Department, Curreio Inc.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06471,unknown,Development of multivalent VHH antibody drug for novel coronavirus infection (COVID-19),,2020,2020,"Drug discovery and development department, Epsilon Molecular Engineering Inc.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06472,unknown,Therapeutic antibody development program for novel coronavirus disease (COVID-19),,2020,2020,"Pharmaceutical R&D Division ,Meiji Seika Pharma Co., Ltd.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06473,unknown,"Development of novel pharmacotherapy to prevent development of severe conditions in patients with COVID-19 and to improve long-term prognosis, and its companion diagnostics",,2020,2020,ARTham Therapeutics Inc.,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Diagnostics | Prognostic factors for disease severity | Pre-clinical studies,2020 +C06474,unknown,Development and product utilization of innovative inhaled exosome medicine for COVID-19-induced severe pneumonia and ARDS,,2020,2020,"Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University School of Medicine",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06475,unknown,Mechanism-based research for discovery of anti-SARS2-CoV-2 drugs,,2020,2020,"Research Institute for Microbial Diseases, Osaka University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06476,unknown,Therapeutic drug development of neutralizing antibody against novel coronavirus (SARS-CoV-2),,2020,2020,"School of Medicine, Keio University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06477,unknown,Development of nucleoside antimetabolites toward emerging / reemerging infectious diseases including novel coronavirus disease (COVID-19),,2020,2020,"Faculty of Pharmaceutical Sciences, Tokushima University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06478,unknown,Development of anti-inflammatory treatment with low dose colchicine for prevention of host inflammatory response phase in patients with novel coronavirus disease (COVID-19) through a physician-initiated clinical trial,,2020,2020,"Department of Respiratory diseases and infection, University of the Ryukyus",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C06479,unknown,"A phase II clinical trial with HLH-94 protocol, etoposide plus corticosteroid combination therapy, for severe illness patients with COVID-19",,2020,2020,"Internal Medicine, Department of Infectious Diseases, Tohoku University",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C06480,unknown,Creation of infectious disease treatment platform by novel nucleic acid therapeutics with remarkably enhanced catalytic target RNA cleavage activities,,2020,2020,"Institute of Multidisciplinary Research for Advanced Materials Professor, Tohoku University",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",,2020 +C06481,unknown,Research and development for establishment of the treatment for COVID-19,,2020,2020,"Disease Control and Prevention Centre, Centre Hospital of the National Center for Global Health",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C06482,unknown,Therapeutic antibody development for novel coronavirus disease (COVID-19) based on deep structural analysis,,2020,2020,"Faculty of Pharmaceutical Sciences, Hokkaido University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06483,unknown,Development of antisense oligonucleotides for the treatment of novel coronavirus disease and establishment of methods for the prediction and evaluation of off-target toxicity,,2020,2020,"Graduate School of Pharmaceutical Sciences, Osaka University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06484,unknown,Development of proteolysis-inducing drugs for COVID-19 and establishment of the off-target evaluation method.,,2020,2020,"Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06485,unknown,Therapeutic drug development utilizing antibody mimetics against SARS-CoV-2,,2020,2020,"Clinical Research Center, National Hospital Organization Nagoya Medical Center",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06486,unknown,Resistance-free SARS-CoV-2 neutralizing drug development with high-affinity modified ACE2 protein.,,2020,2020,"Department of Cardiovascular medicine, Kyoto Prefectural University of Medicine",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06487,unknown,Development of vasoprotective drug for improving the effect of antiviral drug against COVID-19,,2020,2020,"Research Institute for Microbial Diseases, Osaka University",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06488,unknown,Biomarker exploration on novel coronavirus infectious disease (COVID-19) pneumonia for proper treatment,,2020,2020,"Division of Medicinal Safety Science, National Institute of Health Sciences",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,Clinical characterisation and management,Disease pathogenesis,2020 +C06489,unknown,Optimization of amniotic mesenchymal stem cell therapy to treat cytokine storms by COVID-19,,2020,2020,"School of Medicine, Hyogo College of Medicine",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06655,5K08AI139361-02,Social Epidemiology of COVID-19,"Modified Project Summary/Abstract SectionDr. Richardson is an infectious disease physician with doctoral training in anthropology who is establishing himself as a young investigator in clinical and social scientific research of emerging infectious diseases such as Ebola virus and SARS-CoV-2. This K08 award will provide Dr. Richardson with the support necessary to accomplish the following goals: (1) to conduct clinical and social scientific investigations of COVID-19 in sub-Saharan Africa; (2) to learn to design more effective containment strategies for emerging infectious diseases by integrating rigorous ethnographic and epidemiological evidence; (3) to become an expert in the social epidemiology of emerging infectious diseases in low-income settings; and (4) to develop an independent clinical research career. Dr. Richardson has a strong background in clinical infectious diseases and anthropology. This career development award will enable him to address several remaining gaps in the training specific to his career goals. Specifically, he seeks advanced training in (1) epidemiology and (2) biostatistics and will accomplish through coursework at the Harvard School of Public Health. To further achieve his training goals, Dr. Richardson has assembled a mentoring team comprised of: Primary mentors: Dr. Paul Farmer, who conducts anthropological global health research, and Dr. Ichiro Kawachi, a world renown expert in social epidemiology; Advisers: Dr. Megan Murray, an expert in infectious disease transmission dynamics, Dr. Mosoka Fallah, Director of the National Public Health Institute of Liberia (NPHIL), and Dr. Phyllis Kanki, who has decades of virology experience in West Africa. The novel coronavirus which causes COVID-19 was first reported in Hubei Province, China in December 2019. In the ensuing 4 months, the outbreak spread to nearly every country in the world. The arrack rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that 50-60% or more of the global population may become infected as it assumed that nearly all are immunologically naïve. Despite the rapid development of real-time reverse transcription polymerase chain reaction (RT-PCR) testing for detection of virus in infected patients, many questions remain about SARS-CoV-2 seroprevalence and transmission dynamics. This is because many infected cases remain asymptomatic albeit contagious. Moreover, many symptomatic infections go undetected on account of the slow scale-up of RT-PCR testing. These dynamics have their greatest ramifications for healthcare settings, since healthcare workers are one of the few populations that cannot practice social distancing. It is important to know the attack rate in these groups in order to improve infection prevention and control and decrease nosocomial transmission of the virus. This becomes more important in resource-constrained settings, where optimal PPE stocks are difficult to come by. Novel strategies for healthcare interactions may need to be developed in such cases. Accordingly, this study will determine the proportion of asymptomatic SARS-CoV-2 infection and the attack rate amongst African healthcare workers in various settings through serosurveillance (Aim 1). It will also evaluate the role of social and epidemiologic factors in the acquisition of SARS-CoV-2 infection (Aim 2). This research will form the basis for a longitudinal study of the impact of herd immunity and SARS-CoV-2 vaccine rollouts on future pandemic waves.",2020,2023,Harvard University,187920,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,,,,United States of America,,"Epidemiological studies | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Impact/ effectiveness of control measures | Characterisation of vaccine-induced immunity,2019 +C06656,3UM1AI144462-01S2,"Discovery of SARS-CoV-2 neutralizing Abs for therapy, prophylaxis and vaccine development.","This application is being submitted in response to NOT-AI-20-030Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses andthe subfamily consists of only 2 members, Alpha- and Betacoronavirus which infectmammals and generally result in respiratory illnesses.In 2019, the World Health Organization was notified of a cluster of pneumonia casespossibly originating from a seafood market in Wuhan city, Hubei Province, China.Within three weeks, a total of 198 cases of novel coronavirus-infected pneumonia wereconfirmed, and an analysis of 138 cases at the Zhongnan Hospital of Wuhan Universityfound a mortality rate of 4.3%. As of February 25, 2020, there were 79,331 confirmedcases of a clinical syndrome now called COVID-19, as the result of infection by a novelvirus named SARS-CoV-2. The rapid global spread of COVID-19 is possible in partbecause there is no clinically approved treatment or vaccine for SARS-CoV-2.This supplement application will leverage our existing expertise in antibody discoveryand characterization to rapidly identify pan-CoV neutralizing antibodies. Recovered Abswill function both as lead therapeutics to address the ongoing COVID-19 outbreak andtools for evaluating candidate vaccines, by addressing 3 Specific Aims:Aim 1: Isolation of SARS-CoV-2 neutralizing antibodies. Antibodies will be isolatedfrom plasmablasts (acute infection) and memory B cells (convalescence) of COVID-19patients.Aim 2: Characterization of pan-CoV neutralizing antibodies. Isolated mAbs will bescreened for neutralization using a SARS-CoV-2 pseudovirus assay as well as a panelof Betacoronavirus pseudoviruses to determine the breadth of neutralization across theCoronavirus subfamily.Aim 3: Optimization of potency and developability of neutralizing antibodies.Antibodies in the most promising cocktail will be affinity matured to improve their overallpotency and to remove potential manufacturing liabilities.",2020,2026,Scripps Research Institute,188714,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C06657,3R01AI129868-03S1,1) Optimizing eCD4-Ig for eradication and a functional cure,"SAR-CoV-2 (2019-nCoV) is a human pathogenic coronavirus that is very similar to the SARS coronavirus (SARS-CoV or SARS-CoV-1). As of this writing, more than 40,000 people are reported to be infected with this virus, causing more than 1,000 deaths. It is hoped that the number of new cases will decline precipitously in the coming weeks and months, and that newly available therapies can prevent more deaths. However, it is already clear that SARS-CoV-2 will remain a concern, real or potential, over the several next years. The team assembled here has extensive experience the study of SARS-CoV. We identified its receptor - also the receptor for SARS-CoV-2 - as ACE2 (Li et al., Nature 2003), delineated the receptor-binding domain (RBD) on the SARS-CoV spike (S) protein (Wong et al., J Biol Chem 2004), created the first efficient retroviral pseudotype system to study SARS-CoV S protein-mediated entry (Moore et al., J Virol 2004), identified and characterized a broad neutralizing antibody recognizing the RBD in collaboration with Wayne Marasco (Sui et al, PNAS, 2004), described the structure of the RBD bound to ACE2 with Stephen Harrison (Li et al., Science, 2005), described critical S-protein determinants of zoonosis and disease severity (Li et al., EMBO J, 2005), showed in separate collaborations with David Ho and Shibo Jiang that the S protein or the RBD alone can raise potent neutralizing antisera (Chen et al., J Virol 2005; He et al., J Immunol, 2006), and observed that cathepsin L was necessary for S protein-mediated infection (Huang et al., J Biol Chem, 2006). The current proposal seeks to apply this experience and the tools and approaches we developed for SARSCoV to: (1) develop, characterize, and optimize protein inhibitors of SARS-CoV-2 entry including immunoadhesin forms of ACE2, the SARS-CoV-2 RBD region, anti-ACE2 antibodies, and anti-S protein antibodies, (2) determine whether S-protein-trimers or the RBD, or a combination thereof, most efficiently raise SARS-CoV-2 neutralizing antibodies.",2020,2022,Scripps Florida,331181,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C06658,3R01AI148378-01S1,1)MVA based SARS-CoV-2 vaccines,"The overall goal of this proposal is to develop effective prophylactic vaccines against the novel SARSCoronavirus-2 (SARS-CoV-2) infection that has recently emerged as a pandemic across the world. The SARSCoV-2 has already infected more than 120,000 people and over 4000 people died due to COVID-19, a diseasecaused by SARS-CoV-2. Thus, there is an urgent need for the development of a vaccine that can rapidly induceanti-viral immunity and prevent infection. Previous data from other related coronavirus infections such as SARSCoV and MERS-CoV demonstrate that a strong neutralizing antibody response against the spike protein caneffectively prevent infection. Thus, a primary goal of this proposal is to develop a modified vaccinia Ankara (MVA)based vaccine that expresses SARS-CoV-2 spike protein to generate a rapid and strong neutralizing antibodyresponse both in systemic and mucosal compartments. There are several advantages to MVA based vaccinesthat include their excellent safety and a single dose of MVA vaccination can provide protection against multiplevirus infections including SARS-CoV, MERS, Zika and Ebola viruse. A novel aspect of this proposal is that wewill compare the immunogenicity and protective ability of different forms of the spike protein with a goal ofinducing neutralizing antibodies against both SARS-CoV-2 and SARS-CoV. This proposal has two specific aims.The goal of Aim 1 is to generate MVA vaccines and characterizing the anti-spike antibody response in mice. Wewill also compare parenteral (i.m.) vs mucosal (intranasal) vaccinations to determine the best route for inducingmucosal antibody response. The goal of Aim 2 is to evaluate the protective efficacy of the MVA-based SARSCoV2 vaccines. There is an urgent and unmet need to develop and characterize small animal models forevaluating vaccine efficacy against SARS-CoV2. Mice have served as an excellent model system to not onlyunderstand immunity to the related SARS virus but also for evaluating vaccines and antiviral therapeutics. In thisAim, we will develop and characterize a mouse model of SARS-CoV2 infection and use this model to test theprotective efficacy of our MVA-based vaccine candidates. The completion of these studies will not only providea mouse model for SARS-CoV2 infection but also develop vaccine candidates against SARS-CoV2.",2020,2023,Emory University,102106,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Vaccine design and administration,2019 +C06659,3R01AI147884-01A1S1,Structure of the full-length spike protein of SARS-CoV-2 in the context of membrane,"Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses that caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). To meet the urgent needs for diagnostics, therapeutics and vaccines to contain the current crisis, we need to gain deep understanding of structure-function of the viral proteins and the relevant host factors. Viral membrane fusion is the first key step for enveloped viruses, including CoVs, to enter host cells and establish infection. The spike (S) protein of CoV catalyzes membrane fusion by a spring-loaded mechanism, similar to many other class I viral fusion proteins (e.g., HIV envelope spike (Env) and influenza hemagglutinin (HA)), and it is also the major surface antigen inducing neutralizing antibodies. The protein is first produced as a single-chain precursor that trimerizes and may undergo cleavage by a host protease into two noncovalently associated fragments: the receptor-binding fragment S1 and the fusion fragment S2, at the S1/S2 cleavage site. Binding to a host cell receptor (angiotensin converting enzyme 2 (ACE2) for both SARS-CoV and SARS-CoV-2) and further proteolytic cleavage at a second site in S2 (S2' site) are believed to trigger possible dissociation of S1 and irreversible refolding of S2. The large conformational changes in the S protein bring the two membranes close together and ultimately lead to membrane fusion. There have been extensive structural studies of the soluble fragments of the CoV S proteins, including those reported in the last few weeks on SARS-CoV-2, but the structure of the full-length S protein, in particular, in the context of membrane, remains unknown, and yet the regions near the membrane are known to play important structural and functional roles. In a series of recent studies, we have determined the structures of the transmembrane domain (TMD), membrane proximal external region (MPER) and the cytoplasmic tail (CT) of HIV Env in lipid bilayers. We find that these regions all form well-ordered trimeric structures in the presence of a lipid bilayer and that disruption of any of them reduces membrane fusion efficiency and alters the antigenic structure of the entire Env. Based on these results, we hypothesize that the transmembrane and membrane-proximal regions of the CoV S protein also adopt defined oligomeric structures that are critical for the stability, function and antigenicity of the full-length protein in membrane. We will capitalize on the recent advances in cryoEM and lipid nanodisc technology and plan to determine structures of the intact S protein from SARS-CoV-2 reconstituted in lipid bilayers and its complex with human ACE2 or neutralizing antibodies. Our goal is to gain a full understanding of the S protein structure-function and to facilitate vaccine and therapeutic development.",2020,2022,Boston Children'S Hospital,531000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06660,3R01DA046653-03S1,Overdose Risk Management and Compensation in the Era of Naloxone,"Summary of Proposed SupplementThis proposed research undertakes to evaluate the impact of the novel coronavirus pandemic on the parentstudy's sample of 576 adult-age people who use unprescribed opioids. Covid-19 infections in NYC hold thepotential to impact opioid-related overdose risk behaviors-the parent study's main outcome-by changingaccess to naloxone and related health services for people who use drugs. Evaluating the multiplephysiological, psychological, and social domains through which the pandemic can impact opioid-related risk isessential both to understanding the unique vulnerabilities of this population during public health crises and tomaintaining the empirical integrity of the parent grant's aims. Specifically, the population of people who usenonprescribed opioids in NYC is subject to disruptions in their access to naloxone, opioid agonist therapies,and syringe service programs, while social distancing is likely to result in greater incidence of socially isolatedopioid use, diminishing the opportunity for peers or other bystanders to administer naloxone and/or call 911 inthe event of an overdose. The parent study's participant cohort is currently being followed prospectively usingremote, web- and SMS-based survey instruments, which can be modified and expanded to include novelcoronavirus measures. This research supplement will utilize this capacity to achieve the following mixed-method aims which parallel the parent aims and guarantee that the parent grant findings are not confoundedby the enormous physiological and psychosocial impacts of the pandemic on study participants and their opioiduse: a) Examine the impact of the Covid-19 epidemic in NYC on participants' access to and utilization of theoverdose reversal drug, naloxone; b) Evaluate physiological, psychological, and social impacts of thecoronavirus epidemic in NYC as potential predictors of opioid-related overdose risk behavior; and c) Analyzeparticipant and treatment/service provider' perceptions of the processes whereby the coronavirus epidemic hasprecipitated changes in unprescribed opioid use and related overdose risk. By achieving these aims, thissupplementary inquiry will contribute important preliminary understandings of how multiple forms of riskmanagement overlap in the lives of low-income and largely unstably housed people who use opioids. Byproviding timely data on the unique vulnerabilities of this population during an emerging public health crisis, thestudy will be strongly positioned to contribute an empirical base to health policy that mitigates both diseasetransmission and mortality among this at-risk population.",2020,2023,New York University,158343,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Social impacts | Health service delivery,2019 +C06661,3R01DA044206-02S1,Treating Young Adult Cannabis Use Disorder with Text Message-Delivered Peer Network Counseling,"The novel coronavirus disease (COVID-19) pandemic of 2020 has disrupted normal daily functioning forpeople across the globe as governments have sought to limit community spread of the disease. Because thevirus affects the respiratory tract, individuals with compromised lung function, such as those with COPD or lungdisease associated with smoking or vaping may also be at elevated risk. Preliminary evidence suggests thatsmokers are at higher risk for severe COVID-19 illness and death (Guan et al., 2020). Public health messagesurge people to quit smoking (Forster, 2020, and the World Health Organization recommends not smoking orusing other substances to cope with stress during the pandemic (WHO, 2020). At the same time, studiesindicate that individuals are likely in increase their smoking, alcohol intake and substance use during periods ofhigh stress or traumatic events such as Hurricane Katrina or 911 (Flory et al., 2009). Given the urgency andstressful nature of this pandemic, there is a critical need for research investigating the influence of thepandemic on cannabis and tobacco smoking/vaping and other substance use. Directly building upon ourNIDA-funded (1 R01 DA044206-01A1, Treating young adult cannabis use disorder with text messageddeliveredPeer Network Counseling) RCT, we propose to follow a sample of 262 young adults from Tennessee(n = 139) and Colorado (n = 123) who screened positive for cannabis use disorder (CUD) and participated in asub-study named the Cannabis Culture Study. Participants completed surveys about cannabis use behaviors,cannabis use motivations, and cannabis use attitudes between January 9 and February 3, 2020, immediatelyprior to increases in media attention and public health regulations regarding COVID-19. We propose tocapitalize on this longitudinal natural experiment to understand the health risk effects of the COVID-19pandemic on young adults with cannabis use disorder by assessing participants every 3 months for 24 months.Because the funded RCT will also be conducted during the naturally occurring socio-economic and personalchanges in response to the COVID-19 pandemic, this sample of youth will provide a natural comparison groupof how youths' cannabis use attitudes and behaviors change in the context of COVID-19 but outside theexperimental intervention activities. Our specific aims are:Aim1: Examine changes in cannabis, tobacco smoking/vaping, and other substance use as a functionof the COVID-19 pandemic among young adults meeting criteria for CUD.Aim2: Examine mediated pathways by which COVID-19 pandemic affect changes in cannabis, tobaccosmoking/vaping, and other substance use.Aim3: Examine whether the mediated pathways by which COVID-19 pandemic affect changes incannabis, tobacco smoking/vaping, and other substance use are conditioned on sex and stateresidence.",2020,2024,University Of Tennessee Knoxville,125036,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C06662,3R01DA043396-04S1,Immune correlates of long-term success with DAA therapy in HCV/HIV infected people who inject drugs,"Risk factors for developing severe illness/acute respiratory distress syndrome from coronavirusdisease 2019 (COVID-19) include older age, male gender, and underlying conditions, currentlyidentified as smoking, chronic lung disease or moderate to severe asthma, heart disease withcomplications, severe obesity, diabetes, renal failure or liver disease. Immune factors are likelyto contribute to disease progression. While immune activation is required for anti-viral response,severely ill patients show an excessive and aberrant host immune response as evidenced by highinflammatory markers and proinflammatory cytokines. On the other hand, factors associatedwith less robust immune response against the virus, such as advanced age are associated withsevere disease. Opioid use disorder (OUD) is an important public heath condition associated withdysregulated immunity. This may be related to higher prevalence of systemic comorbidconditions and concomitant conditions like chronic HIV, hepatitis C or incident infectionsrelated to injection drug use, which may further influence immune response to infections. Anespecially vulnerable group is people living with HIV (PLWH) with OUD, which are expected tohave further immune dysregulations due to twin effect of HIV and opioids on immunity.Additionally, people with OUD are at increased risk of COVID-19 due to social factors suchas homelessness, poor access to healthcare, housing insecurity, greater likelihood ofincarceration, which can make it more difficult to maintain social distancing and theseindividuals may not seek medical care promptly due to lack of access to outpatient care. We areasking whether OUD constitutes a risk factor for progressive (COVID-19), especially in PLWH.We are investigating immune responses in individuals with OUD and HIV infection under ourNIDA funded R01; leveraging the clinical cohorts and IRB approved blood collection protocolsfrom COVID-19 patients, here we will investigate incidence and progression of COVID-19 inthese patient populations. First, we will document clinical course and outcomes of COVID-19 inpatients with or without OUD/HIV. To identify immune correlates of COVID-19 severity, wewill perform analysis of B and T cell responses and study impact of OUD and HIV on thisresponse. Our investigation of clinical and immunological features of the disease in PLWH andOUD will expand on known correlates of progressive COVID-19 and will inform treatment andprophylactic approaches for COVID-19 in vulnerable groups.",2020,2022,University Of Maryland Baltimore,154500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2017 +C06663,3P30CA016058-44S2,Impact of COVID-19 on Behaviors across the Cancer Control Continuum in Ohio,"COVID-19 has impacted all countries in the world. No populations remain untouched by either direct or indirecteffects. Social distancing, isolation and a variety of challenges related to employment and access to basic needsare impacting every facet of everyday life. The impact of these COVID-19 restrictions and disease must bequantified to understand and mitigate short and long term effects across the cancer continuum, especially amongthe most vulnerable - underserved and minority populations and cancer patients. The goal of this study is toassess how differences in demographics (rural/urban, age, gender, race, educational attainment) will impactengagement in cancer preventive behaviors (e.g., tobacco cessation) and cancer management/survivorshipbehaviors (e.g., adherence to treatment, adherence to surveillance) in the context of COVID-19 environmentalconstraints (e.g., social distancing, employment, mental health, etc.) among adult healthy volunteers, cancerpatients, and cancer survivors in Ohio, our catchment area.",2020,2020,Ohio State University,156000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Social impacts,1997 +C06664,3P30CA118100-15S5,Development of Epitope-Targeted SARS-CoV-2 Vaccines,"A vaccine against SARS-CoV2 is badly needed. We have developed a vaccine platform technology based on virus-like particles (VLPs) of RNA phages like MS2, PP7, AP205 and Qß. When displayed multivalently on these bionanoparticles, peptide and protein antigens acquire a high level of immunogenicity. They elicit high titer and long-lived antibody responses to virtually any displayed antigen. Moreover, the VLP platform has rapid response potential to quickly counter emerging threats. Here we describe an approach to the display of SARS-CoV2 epitopes, and tests of their ability to elicit neutralizing and protective antibodies in mice. Our approach consists of three specific aims: In Aim 1, we will Identify candidate vaccine epitopes for SARS-CoV2 and endow them with high immunogenicity by displaying them on VLPs. This virus shares sufficient sequence and structural homology with SARS-CoV1 to allow us to infer likely neutralizing epitopes from knowledge of the targets of its neutralizing antibodies. Accordingly, we describe strategies for display and optimization of spike protein epitopes we predict will elicit antibodies that will separately inhibit two essential steps in virus entry - receptor binding and virus-cell fusion. In Aim 2, we will immunize mice with candidate VLPs and will use ELISA to quantify the resulting antibody responses, testing the reaction of sera with recombinant spike protein and with synthetic peptides representing the chosen epitopes. In Aim 3, the neutralization activity of sera will be tested by plaque reduction neutralization tests in cultured cells. Subsequently, we will vaccinate mice transgenic for human ACE2 (the SARS-CoV2 receptor) and test their abilities to resist the effects of SARS-CoV2 infection.",2020,2021,University Of New Mexico Health Scis Ctr,373749,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2005 +C06665,3U19AI118610-06S1,Mount Sinai IMPACC COVID-19 Cores,"As part of an NIAID/DAIT initiative we have been selected to participate in a multicenter project, namelyImmunophenotyping assessment in a COVID-19 Cohort (IMPACC), aimed to collect and distribute patientsamples and to and analyze the immune responses of 2000 COVID19 patients using specific designatedcores. The main purpose of this nationwide immunophenotyping protocol in high impact COVID-19 areas isto perform detailed immunophenotyping and analysis of the host factors that may predict or predispose toresolution of infection versus disease progression and its consequences. The protocol has been designed toinform disease progression dynamics and related biomarkers; and conduct detailed, longitudinalimmunophenotyping (presentation through disease progression) that includes measures of viral load tounderstand the interplay between viral load and immune pathology in disease progression. There is anemphasis on the clinical progression by including all aspects of clinical characterization that will be neededto match immunopathogenesis with each disease stage within each patient. IMPACC builds on the cohortsand clinical resources and technology developed by the NAIAD/DAIT funded Clinical centers for HumanImmunology (CCHI) and the Human Immunology Project Consortia (HIPC). Thus, our team has beenselected by DAIT to participate, since Dr. Fernandez-Sesma is currently the PI of one of the HIPC centers,named DHIPC, which studies human immune responses to dengue, chikungunya and Zika virus infectionand vaccination and Dr. Adeeb Rahman is also a crucial member of the same HIPC center and will be theImmonophenotyping core leader for this application. Additionally, other members of the team have beenselected to participate based on their expertise in clinical sample collection and processing in hospitalsettings to analyze responses to respiratory viral infections, including viral sequencing and viral loadmeasurement. Thus, this administrative supplement to our parent HIPC grant, named Mt Sinai IMPACC iswithin the scope of our parent HIPC award, since it is focused on the study of human immune responses to aviral infection. The team gathered for this application includes Dr. Viviana Simon, leading the clinical/samplecollection core, Dr. Adeb Rahman, that will lead the immunopheotyping core, Dr. Florian Krammer, leadingthe serology Core, Dr. Harm Van Bakel, leading the virus sequencing core as well as Dr. Adolfo Garcia-Sastre as a co-investigator and Dr. Jaime Hook as a pulmonologist in the clinic. With this team and theavailability of clinical samples and the appropriate resources and biocontainment at our site we are poised toprovide samples and to analyze the different immune and viral parameters that will help us understanddisease severity and progression in during the COVID19 pandemic. Mount Sinai Hospital is located in NewYork City, which is at the epicenter of this pandemic in the US and is already treating hundreds of COVIDpatients.",2020,2021,Icahn School Of Medicine At Mount Sinai,5198360,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity",2020 +C06666,3U45ES006155-29S1,AFC Hazmat Worker Health and Safety Training Cooperative Agreement (U45),"AFC Supplement 2020 Project Summary: With this application, the Alabama Fire College (AFC) requests supplemental funding to conductCOVID-19 specific health and safety training with public safety personnel, including healthcareworkers and others that are considered essential workers during the COVID-19 response.Using current Bureau of Labor Statistics, there are over 556,000 public safety and healthcarepersonnel working in the region including those who will provide patient transport or aremembers of emergency response teams and have roles which will require them to respond toan infectious disease outbreak such as the COVID-19 pandemic. Most of these personnel workin rural areas or medically underserved areas which put them and the patients they serve atgreater risk. All these target populations have in common the potential for exposure to personsinfected with COVID-19 and other emerging infectious diseases, through direct contact withinfected individuals as well as through surface contamination or other contaminated materials.Alabama and Mississippi contain many medically underserved areas, health professionalshortage areas, health department with limited budgets and limited ability to conduct contacttracing, and limited access to professional occupational safety and health training programs.Unfortunately, federal funds for preparedness assistance have not reached public safety andhealthcare professionals in the amounts sufficient to meet their needs for training. AFC and it'spartner, UAB, will develop and implement evidence-based training tools that are locally-relevantand consistent with the NIEHS WTP Coronavirus Bio-safety Initiative and guidance from theCenters for Disease Control and Prevention (CDC), the Occupational Safety and HealthAdministration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), aswell as other recognized health professionals. The proposed project will bring critical training toover 400 participants in webinar, virtual simulation, YouTube video, and limited in-persontraining. Courses will also be available through AFC's learning management system to NativeAmerican tribes and other responders and essential workers, adding many potential traineesthrough distance education.",2020,2020,Alabama Fire College,200000,Not applicable,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,Health workforce,1992 +C06667,3P30CA086862-20S3,The Impact of COVID-19 and Social Distancing on Cancer-Related Behaviors,"Given the wide variability in communication and restrictions across communities in the U.S. in response to the COVID-19pandemic, the extent to which people across the country are changing their behaviors to mitigate risk of transmission isunknown. Furthermore, it is difficult to anticipate how changing behaviors in response to COVID-19 could impact cancerrelated behaviors and risk factors; exercising, drinking, smoking, diet and stress could be profoundly impacted as a resultof social distancing and self-isolation. Furthermore, different populations may be impacted in very different ways. Forexample, Iowa is among the handful of predominantly rural states that have not yet implemented a statewide shelter inplace order, citing lower risk of infection in rural areas. Yet in this first week of April, the case rate in rural areas hasmore than doubled from one week prior, and widespread testing is not available to assess the true extent of the casecount. It has also been reported that in rural areas without reliable internet access, adults are struggling to workremotely, and children are having to get school assignments delivered to their door.1 Furthermore, rural communitiesmay have diminished access to health information, healthcare services, grocery stores and pharmacies.As a multicenter group of cancer researchers already invested deeply in understanding and improving health outcomesin our catchment areas, we propose to rapidly deploy surveys containing a standard set of core questions to populationsacross the U.S. The overall objective of our collaborative effort is to assess how differences in demographics (rurality,age, gender, race, educational attainment) will impact engagement in cancer preventive behaviors (e.g., tobaccocessation) and cancer management/survivorship behaviors (e.g., adherence to treatment, adherence to surveillance) inthe context of COVID-19 environmental constraints (e.g., social distancing, employment, mental health, etc.) among thegeneral adult populations, cancer patients, and cancer survivors in Iowa.",2020,2021,University Of Iowa,154500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2000 +C06668,3P30CA023108-41S5,COVID19 Pandemic: Natural Experiment in Rural Cancer Care Telemedicine Capacity Building,"The COVID-19 pandemic has catalyzed an unprecedented need to deliver ongoing care for cancer and other chronic conditions remotely. Telemedicine has long been touted as an underused, but promising, mode of delivering care to rural areas. Successful care delivery models, such as teleconsultation and telementoring, have become more prevalent in the past decade, yet are underutilized in rural areas. Assessing telemedicine capacity within geographic areas is critical for regional planning to serve rural populations' cancer care needs. Telemedicine is a focus of the Rural Supplement to the CCSG for the Norris Cotton Cancer Center (NCCC), with a community-partnered environmental scan of telemedicine capacity underway within our catchment area (NH/VT). Within weeks of confirmed COVID-19 patients in our region, NCCC providers from most ambulatory services transitioned to televisits for a large portion of patients. This extremely rapid expansion of telemedicine services, arising from a public health crisis, will have unknown effects on telemedicine capacity post-pandemic. A persistent increase in capacity and/or readiness to sustain telemedicine care delivery may be a positive unintended consequence of this unprecedented population-wide social isolation. NCCC's precipitous shift of health care delivery to remote modes, leveraged with our ongoing catchment area work, provides a unique opportunity to conduct a natural experiment in telemedicine capacity-building. Using a mixed methods approach to evaluate the multilevel impact of this natural experiment we will test underlying capacity for telemedicine and its sustainability, addressing: a) mobilization of information technology resources; b) rapid development of service delivery pathways; c) clinical information integration; d) attitudinal shifts of patients, providers and health system managers, and the interplay of telemedicine with social determinants of health for our cancer population; and e) payment models. Our specific aims are: Aim 1) Document changes in telemedicine capacity, use, and outcomes across the cancer care continuum by gathering data at multiple levels including patient, provider, health system and policy/contextual; Aim 2) Evaluate the factors associated with sustained telemedicine capacity, use, and outcomes following the COVID-19 pandemic based on Aim 1 multilevel data; Aim 3) Collaboratively document and share lessons learned regarding the impact of the COVID-19 pandemic on telemedicine cancer care delivery with other cancer centers funded to study telemedicine through the CCSG supplement mechanism.",2020,2024,Dartmouth College,204000,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,1997 +C06669,3P30CA068485-24S4,The COVID-19 and Cancer Consortium (CCC19),"COVID-19, the disease caused by the SARS-coV-2 virus, has now affected at least 1,200,000 people globally, and cases are accumulating in an exponential fashion in many countries, including the United States. Cancer patients have a unique risk profile in this pandemic. Many patients, especially those actively on treatment, have high levels of contact with the health care system. This can include provider visits, phlebotomy, imaging, social work and financial consultations, and infusion room visits for anti-cancer therapy and supportive care such as blood transfusions. Despite heroic efforts to reduce viral transmission in these shared spaces, patients are at an increased risk for COVID-19 exposure. Additionally, most cancer patients are immunocompromised through the marrow toxic effects of anti-cancer drugs, supportive medications such as steroids, and/or the cancer itself; and over 60 years of age, putting them in the highest-risk category for COVID-19-related morbidity and mortality. Finally, incidences of important comorbidities can be considerably elevated in several cancers, such as chronic obstructive pulmonary disease in lung cancer or inflammatory bowel disease in colorectal cancer, further exacerbating our patients' vulnerability to this novel pathogen. Early reports on prognosis for cancer patients are conflicting and, for the most part, non-peer-reviewed. The largest study published to date includes 18 patients with cancer, who were shown to have increased risk for severe events in multivariate analysis. Lung cancer was the most common malignancy in this cohort, comprising 5 of the 18 cases (28%). Importantly, only five of the 18 patients were known to be on active systemic anti-cancer therapy. Still, these small patient numbers do not reflect the true impact of COVID-19 on cancer patients, particularly patients on active treatment. Given this acute lack of knowledge and concern for extreme vulnerability, the COVID-19 and Cancer Consortium was formed to understand how the novel virus affects cancer patients. While this national effort began organically, primarily through social media, membership has quickly grown to over 130 physicians and nurses representing over 60 institutions and organizations in the US. Included in this membership, thus far, are 35 NCI-designated Comprehensive Cancer Centers, as well as 6 NCI-designated Cancer Centers and large networks of community practices. The driving goal of the consortium is to collect prospective, granular, uniformly organized information to help generate hypotheses for translational science, and to arm treating providers with the most complete data resource as rapidly as possible on cancer patients infected with COVID-19. As the Coordinating Center for the consortium, we will establish and propagate best practices for governance, data collection, and data dissemination. We will host the main data registry and will work with participant institutions setting up mirrored local databases. We will also pilot a prospective biospecimen collection protocol focused on determining whether clonal hematopoiesis in cancer patients with COVID-19 alters their risk profile.",2020,2020,Vanderbilt University Medical Center,595000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,1997 +C06670,3UM1AI144462-02S1,Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antivirals,"Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses and are divided into Alphaand Beta-coronaviruses. CoVs infect mammals and birds and typically result in lower and/or upper respiratory tract disease. The spectrum of illness in humans caused by CoVs range from common colds to worldwide epidemics/pandemics, including severe acute respiratory syndrome (SARS-CoV) in 2003, human CoV-NL63 in 2004, human CoV-HKU1 in 2005, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. There are no approved vaccines or antiviral drugs to combat CoV infections and a lack oftested and validated therapeutics represents a tremendous global concern with respect to the current SARSCoV-2 outbreak. At the end of December 2019, the World Health Organization became aware of an abnormally large cluster of pneumonia cases localized in the city of Wuhan, China. Within a span of only 3 months, over one million confirmed cases of COVID-19 have been diagnosed worldwide with almost 50,0000 resulting in death. The numbers in the US are now growing at an alarming rate (currently ~25% of the global total) as well as the numberof deaths (currently ~10% of total). The severity of human CoV infections and high mortality rates were strikingly apparent in 2002 with the first SARS-CoV pandemic in Guangdong, China, as well as the MERS-CoV outbreak in 2012. Like SARS-CoV, the current SARS-CoV-2, which is 79% identical, also employs angiotensin converting enzyme II (ACE2) as the host receptor for cellular entry. The CoV surface-exposed spike (S) protein is responsible for the recognition and binding of ACE2 and represents a potential target for development of vaccines and antiviral therapeutics. Importantly, antibodies (Abs) isolated to date from COVID-19 patients appear to bind several regions on the spike protein that then represent ideal targets for small molecule discovery.The spike protein on the CoV surface is a glycosylated trimer and consists of two extracellular domains, S1 and S2. The majority of nAbs (neutralizing Abs) to CoVs characterized to date target the S1 domain that contains the receptor-binding domain (RBD) responsible for ACE2 binding. Notwithstanding, Abs with epitopes on the S2 domain, consisting of the stem fusion machinery, also have neutralizing potential in both cell-based and animal models of infection and are generally more broadly reactive against other CoVs than those antibodies that targetS1. Additionally, a helical peptide EK1 derived from the HR2 domain of human CoV-OC43 (a strain responsible for the common cold) broadly binds to the stem region of CoVs and inhibits membrane fusion. Our goal with this supplement is to define the neutralizing epitopes on the S protein of SARS-CoV-2, such as those targeted by antibodies, the EK1 peptide and other peptides reported to bind to the RBD, to aid in both structure-based vaccine and small molecule antiviral design. Specifically, we will leverage our combined expertise in x-ray crystallography (Wilson), electron microscopy (Ward), and small-molecule discovery and medicinal chemistry (Wolan) to functionally characterize neutralization epitopes and antibody binding motifs and apply this information into high-throughput assays to aid in vaccine design, applications and use of therapeutic antibodies, and for discovery of specific high affinity small molecules to the S protein of SARS-CoV-2, as well as other coronaviruses, including SARS and MERS. We anticipate thatour structural characterization of novel Abs isolated from B cells of convalescent patients will provide critical information on surface hot spots, which can be targeted by vaccines and small molecules. As such, common features employed by antibodies for epitope recognition will inform on the tailored design of compounds as lead candidates for COVID-19 antivirals. Importantly, we will subject our small molecules to biologically relevant pseudovirus plaque assays and cell-based infection models, as well as human microsomal stability assays to generate a compendium of small molecules to move forward into translational studies.",2020,2022,Scripps Research Institute,816869,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies | Pre-clinical studies",2020 +C06671,3UL1TR003096-02S2,1) Center for Clinical and Translational Science,"Abstract: The pandemic prompted by the novel SARS-COV-2 virus continues to have a devastating impact on the healthof communities, clinically, socially and economically. Preventive approaches require an understanding of thevirus prevalence and herd immunity in the general population. To evaluate the sero-prevalence of immunityagainst SARS-COV-2 in the United States, this scientific partnership of academic medical centers and theNIH's intramural research program will examine the population prevalences of detectable antibodies to SARS-COV-2 from a convenience sampling of adults in the U.S. who have not been diagnosed with COVID-19 (Aim1) and will determine the immune attributes associated with health outcomes (Aim 2), including for those inunderrepresented populations and across the life course. From a cohort of >400,000 self-referred,asymptomatic adults nationwide, a near-representative subset will be selected based on demographics suchas age, race/ethnicity, and geography to provide blood samples for characterization of antibodies and otherimmunologic markers to inform the development of screening and neutralization assays. This work benefitsfrom the deep expertise in the basic and applied research of infectious diseases as well as viral vaccinedevelopment, host immune response to viruses, and viral molecular biology and genetics at the NationalInstitute for Allergy and Infectious Diseases (NIAID). It also leverages the rigorous and efficient capacitymaintained by Clinical and Translational Science Awards (CTSA) Hubs to rapidly engage diverse cohorts ofparticipants nationally to accelerate translational research that is high priority scientifically and for eventualpublic health practice. From this study, the collaborative team will gain crucial insights into the magnitude of theCOVID-19 pandemic across the country and will identify potential targets for a vaccine. These data areessential to assess the impact of public health efforts and to guide ongoing COVID-19 response.",2020,2024,University Of Alabama At Birmingham,587941,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2019 +C06672,3UL1TR001857-05S1,1) University of Pittsburgh Clinical and Translational Science Institute,"Abstract: The pandemic prompted by the novel SARS-COV-2 virus continues to have a devastating impact on the healthof communities, clinically, socially and economically. Preventive approaches require an understanding of thevirus prevalence and herd immunity in the general population. To evaluate the sero-prevalence of immunityagainst SARS-COV-2 in the United States, this scientific partnership of academic medical centers and theNIH's intramural research program will examine the population prevalences of detectable antibodies to SARS-COV-2 from a convenience sampling of adults in the U.S. who have not been diagnosed with COVID-19 (Aim1) and will determine the immune attributes associated with health outcomes (Aim 2), including for those inunderrepresented populations and across the life course. From a cohort of >400,000 self-referred,asymptomatic adults nationwide, a near-representative subset will be selected based on demographics suchas age, race/ethnicity, and geography to provide blood samples for characterization of antibodies and otherimmunologic markers to inform the development of screening and neutralization assays. This work benefitsfrom the deep expertise in the basic and applied research of infectious diseases as well as viral vaccinedevelopment, host immune response to viruses, and viral molecular biology and genetics at the NationalInstitute for Allergy and Infectious Diseases (NIAID). It also leverages the rigorous and efficient capacitymaintained by Clinical and Translational Science Awards (CTSA) Hubs to rapidly engage diverse cohorts ofparticipants nationally to accelerate translational research that is high priority scientifically and for eventualpublic health practice. From this study, the collaborative team will gain crucial insights into the magnitude of theCOVID-19 pandemic across the country and will identify potential targets for a vaccine. These data areessential to assess the impact of public health efforts and to guide ongoing COVID-19 response.",2020,2021,University Of Pittsburgh At Pittsburgh,750000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2016 +C06673,3P30CA022453-38S4,Cancer Center Support Grant,"Cancer is the second leading cause of death in the state of Michigan. However, expected cancer mortality in 2020 may be underestimated due to the COVID-19 pandemic. The pandemic is a public health crisis that has dramatically altered almost every dimension of daily life in the U.S. Michigan ranks fifth among states in COVID-19 incidence and mortality, largely driven by the predominantly African American city of Detroit, which accounts for one-third of Michigan's COVID-19 cases. COVID-19-related disruptions in daily life and routines may have a broad range of adverse consequences including limited access to care, resources, and information, as well as psychological distress that undermine prevention and control efforts at the population and individual level and across the cancer care continuum. Therefore, we propose to participate in a consortium of NCI-designated cancer centers who will rapidly deploy surveys containing a standard set of core questions to populations across the U.S. The broad goal of the proposed research is to assess how differences in demographics (rural/urban, age, gender, race, educational attainment) will impact engagement in cancer preventive behaviors (e.g., tobacco cessation) and cancer management/survivorship behaviors (e.g., adherence to treatment and surveillance) in the context of COVID19-related environmental constraints (e.g., social distancing, employment, mental health, etc.). This research will be conducted among the general adult population, cancer patients, and cancer survivors within Karmanos Cancer Institute's 46-county catchment area in Michigan. Further, this work will be aligned with the efforts of a COVID-19 Population Science (CPS) Consortium that includes University of Iowa Holden Comprehensive Cancer Center, the James Comprehensive Cancer Center at the Ohio State University, University of Colorado Cancer Center, and the O'Neal Comprehensive Cancer Center at University of Alabama - Birmingham as the coordinating site. There are three specific aims. Aim 1: Develop a core set of questions to assess community and individual responses to the COVID-19 pandemic across populations, along with modules that will apply to specific sub-populations in any given catchment area. Aim 2: Administer the core set of questions and locally relevant modules to 2000 adults to determine the association between COVID-19 responses and cancer prevention and control behaviors among the general adult population, cancer patients, and cancer survivors in the KCI catchment area in Michigan, with a focus on racial and rural-urban differences. Aim 3: Develop and implement strategies to increase access to appropriate cancer resources based on survey results, in partnership with stakeholder organizations throughout the catchment area and evaluate their reach in the population. The proposed work represents an extraordinary opportunity to capture the impact of this public health crisis on cancer care and outcomes. This research will also shed new light on the social determinants that drive racial disparities in cancer specifically, and health more broadly. Data will also inform practical strategies to support vulnerable populations that disproportionately carry COVID-19 burden.",2020,2020,Wayne State University,154000,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Policy research and interventions | Indirect health impacts | Health service delivery,1997 +C06674,"1OT2HL156812-01, -01S1, -01S3, -01S4",ACTIV Integration of Host-targeting Therapies for COVID-19 Administrative Coordinating Center,"RTI International is pleased to provide this application as requested by the Research OpportunitiesAnnouncement OTA-20-011 ACTIV Integration of Host-targeting Therapies for COVID-19 for the roleof Administrative Coordinating Center (ACC). The title of our application is ACTIV Integration ofHost-targeting Therapies for COVID-19 Administrative Coordinating Center.The Integration of Host-targeting Therapies for COVID-19 Program aims to identify COVID-19interventions relevant to heart, lung, blood, and cardiovascular outcomes that contribute to the scientificknowledge base are likely to inform clinical practice. This Program will rapidly and efficiently conductadaptive platform trials via a coordinated effort of Data Coordinating Centers and clinical sites fromexisting Clinical Study Networks. The ACC is a critical component of the Program. We will coordinatewith NHLBI to ensure collaboration among networks including the use of standardized approaches inclinical trial design and conduct, data collection and validation, and statistical analysis such that studiesare launched, implemented and analyzed swiftly; and study findings are scientifically sound and meetregulatory needs for medical therapy development. As the ACC, we will also serve the vital role offacilitating communication and information sharing among all relevant stake holders and helping NHLBIin tracking study-specific and Program-wide milestones.Sonia Thomas, DrPH, will lead the ACC as Principal Investigator. She is an experienced CC PI andstatistician with 25 years of experience in the design, implementation, and analysis of multicenter NIHandindustry-sponsored Phase 2-4 clinical trials of drugs, biologics, devices, surgical and behavioralinterventions in more than a dozen therapeutic indications. Dr. Thomas will be supported by TracyNolen, DrPH as Alternate PI, an experienced Consortium and CC PI and clinical trial statistician, andsubject matter experts Steve Nissen, MD, Cleveland Clinical Chief Academic Officer, Heart andVascular Institute, Shannon Carson, MD, Univ. of North Carolina Chief of Pulmonary and Critical CareMedicine, and Anastasia Ivanova, PhD, Univ. of North Carolina Professor of BiostatisticsUnder Dr Thomas's direction, our team will lead, support, and collaborate with Program Networksthrough organization into 6 ACC Cores: Program Operations, Scientific Leadership andPrioritization, Informatics, Data Standards, Study Design, Implementation, & Analysis, andRegulatory and QA. We have identified milestones for the essential activities of the ACC within each ofthese 6 Cores with a detailed focus on the activities in the first 6 months as activities completed duringthis time are most important for ensuring the coordinated, expedited and efficient launch of this Program.Dr. Thomas, our subject matter experts, senior statistical scientists, and many of the core leads havesubstantial experience with NHLBI and thus understand the needs and priorities of the Institute and willuse this knowledge to better collaborate with NHLBI and further speed up the launch of this Program.We are willing to collaborate with all involved entities as part of the overarching trans-NIH ACTIVProgram as it evolves. We recognize and anticipate that swift adaptation will be required to rapidlyrespond to the urgent clinical research needs to address the COVID-19 pandemic.RTI is uniquely and substantially qualified for the ACC. We will use our team's broad experience frommany complex coordinating center projects to anticipate the needs for this Program and ""hit the groundrunning"". Proven informatics technology in use by existing NIH programs will be swiftly modified byour analysts for speedy deployment of communications platforms. Our organizational size and flexibilitywill allow us to ramp up quickly and modify personnel resources flexibly. Lastly, RTI has a proven trackrecord of successful collaborations with other coordinating centers on complex programs, yet as we arenot directly involved with any Networks for consideration to be NHLBI COVID-19 trials sites, weprovide independence and objectivity to the Program.",2020,2022,Research Triangle Institute,312370025,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trial (unspecified trial phase)",2020 +C06675,3R44DA048712-01S1,RCT of Woebot for Substance Use Disorders,"PROJECT SUMMARY / ABSTRACTWoebot for Substance Use Disorders (W-SUDs) is a two-phase NIDA-funded SBIR. Presently,W-SUDs, a novel digital therapeutic, is being evaluated in the Phase I pilot. Phase II willinvestigate W-SUDs's efficacy compared to an active control condition. Since the initial award,and across mere months, Covid-19 became a global pandemic, and users worldwide came toWoebot to discuss it and seek help. The company responded by building and deploying Covid-19 specific programming (W-C19) in March 2020. W-C19 elements have been integrated intoW-SUDs; we felt it was timely and appropriate to address users' concerns about the pandemicand demonstrate that Woebot was 'intelligent' to the crisis. Experts expect Covid-19's direct andindirect impact upon individuals with SUDs to be particularly heavy. These individuals oftenhave physical vulnerabilities, which increase the relative risk of death from Covid-19, and facelimited health care access -- fundamentally challenging given often comorbid mental illness.Moreover, high rates of housing insecurity hinders compliance with shelter-in- place and socialdistancing recommendations, thereby increasing contagion risk. This proposal, with the timelyaddition of a randomized controlled trial comparing W-SUDs to a waitlist control (WL),expands understanding of W-SUDs' efficacy whilst investigating Covid-19's impact uponthe SUD population. Secular trends of increased substance use are anticipated given Covid-19stressors (e.g., shelter-in- place, disease concerns, economic strife, under-/unemployment).Hence, the WL condition is essential for testing W-SUDs' efficacy in mitigating these Covid-19related downstream effects. This proposal extends the parent grant by: (i) adding a randomizedcontrolled evaluation of W-SUDs compared to WL and (ii) investigating potential between groupdifferences on (a) substance use, (b) Covid-19 related components (e.g., social distancing;employment and parental factors), and (c) other SUD treatment engagement. While 20.2 million(8.4%) American adults had a SUD within the past year, only 20% received treatment, givensignificant treatment access barriers [1]. W-SUDs: (i) is poised to reduce or eliminate commonyet significant barriers to traditional SUD treatment; (ii) offers virtual access, optimal for sociallydistancing and shelter-in-place adherence; (iii) has unconstrained and immediate scalepotential; and (iv) delivers content text-based conversation, optimal for engagement. This studyoffers immediate access to a digital therapeutic in a resource constrained, socially distancedhealthcare ecosystem for an already vulnerable and underserved population, likely faced withreadily growing psychological challenges.",2020,2020,"Woebot Labs, Inc.",139951,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C06676,3U54AI117804-06S1,Consortium of Eosinophilic Gastrointestinal Disease Researchers-HEROs Supplement,"Project Summary/Abstract: This Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) study will enroll approximately 150families to assess how SARS-COV-2 differentially affects children with Eosinophilic GastrointestinalDisorders (EGIDs) compared to children without these disorders. The proposed work is part of the largerHuman Epidemiology and Response to SARS-CoV-2 (HEROS) study that allows a comparison betweenchildren with atopic conditions and children without those conditions. Although asthma has not beenidentified as a clear risk factor for severe COVID-19 disease, there is evidence that children with asthmaand other atopic conditions have increased susceptibility to viral respiratory infections (Esquivel etal, AJRCCM, PMC5649984) and that viral respiratory infections may result in worsening of underlyingairway disease (Jartti et al, J Allergy Clin Immunol, PMID 28987219). No data currently exist as towhether this is true for SARS-CoV-2 infection or whether allergic airway disease could beprotective. Enrolled families will participate for 6 months completing surveys and biological samplecollections. These children and their families are already enrolled in the CEGIR NIH funded studies andtherefore will overcome many challenges for clinical study implementation. This proposed workremains in scope to the parent award and is responsive to the NOT-AI-20-031.",2020,2021,Cincinnati Childrens Hosp Med Ctr,114280,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C06677,3U19AI082630-12S1,Impact of Immunotherapy on Viral Immunity in Humans,"COVID-19 disease (caused by SARS-CoV-2) typically manifests as a period of low-grade illness followed byprogression in some to an acute phase illness after 7-10 days characterized by pneumonia, and progression toARDS, cytokine release syndrome, and multiorgan failure at 10-14 days. This progression is thought to reflectsome combination of increasing viral load, cytopathic effects, translocation into lower airways and other tissues.During acute respiratory viral infections, pathology and disease can result from either an insufficient or anoveraggressive immune response. In the case of COVID-19 disease it is unclear which side of the diseasepathology spectrum predominates and whether this differs in patients with mild versus severe disease or overthe course of disease in an individual patient. In general, we know little about the immune response to COVID-19 disease, which cell types contribute to control and mild disease and which are involved in severe disease.Moreover, in patients who successfully control disease and recover, we know nothing about immunologicalmemory. There are major questions about the nature of the innate and adaptive immune response duringCOVID-19 disease that can be directly addressed by the unique infrastructure of our existing U19. For example,using our expertise on innate immune cells including myeloid cells, dendritic cells and MAIT cells, we can addressthe following questions: Are these (and other) innate immune cells activated and do these activation stateschange with disease severity or over time? Do these innate immune cell responses link to the responses ofadaptive immune cells? Similarly, our expertise in adaptive immunity can be leveraged to address the followingquestions: How do CD4 T cell responses including Tfh and CD8 T cell responses relate to COVID-19 disease? CanB cell responses to the virus be detected? What happens to these cells in convalescence? Is immunologicalmemory established? Are the same B cell and T cell clonotypes responding in the acute phase and followingresolution? Are immune cells altered by the initial virus challenge, leading to aberrant responses in the secondweek when the virus re-emerges at a new site (alveoli, heart or other sites)? Which adaptive immune responsesprovide protection against the virus? Working with blood and tissue samples from COVID-19 cohorts at UPennand MGH, we will study T cell responses in relation to severity and stage of disease (including kinetics, activationand differentiation states, development into memory and repertoire), B cell and antibody dynamics andrepertoire at different stages of disease, monocyte populations and attendant cytokines as key determinants ofoutcome in COVID-19 disease. We will share de-identified datasets rapidly with the community (following initialquality assessment) via outward-facing portals.",2020,2022,Massachusetts General Hospital,1126470,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2009 +C06678,3UM1AI069423-14S1,HIV/AIDS Clinical Trials Unit (CTU) COVID-19 Admin Supplement,"Project Summary/Abstract: The University of North Carolina (UNC) Global HIV Clinical Trials Unit (CTU) has a wellestablished track record of high-quality, innovative clinical research, strong scientific leadership(both in and outside the NIH HIV/AIDS Networks), and access to critically important infected andat-risk populations in the Southeastern US, Southeast Asia and in Southern Africa. Drawn froma diverse team of clinical innvestigators spanning two continents, our is led by experiencedprincipal investigators (Joseph Eron MD and Mina Hosseinipour MD) and will support all 5 NIHHIV Clinical Trials Networks: Adult Therapeutic Strategies, Strategies to Address HIV and HIV-associated Infections in Pediatric and Maternal Populations, Integrated HIV PreventionStrategies, Microbicide Strategies, and Vaccine Strategies to Prevent HIV Infection. The ClinicalResearch Sites (CRS) include Chapel Hill CRS led by David Wohl MD (Adult TherapeuticStrategies, Integrated Prevention, Microbicide and Vaccine), Greensboro CRS led by CorneliusVan Dam MD PhD (Adult Therapeutic Strategy and Integrated Prevention), Malawi CRS led byLameck Chinula MD (all 5 Networks) and Vietnam (protocol specific site) led by Vivian Go.Supporting this leadership is a well-organized research team, comprising global experts and sitecollaborators who will work to execute the network scientific agendas. The CTU has alsoassembled a diverse group of senior scientists and public health officials to serve on ourScientific and Strategic Advisory Group. The CTU administration incorporates a highlyorganized structure that will be responsive to our experienced research teams across the CRSand will provide ongoing evaluation to ensure optimal performance and efficiency. The CTU issupported by state-of-the-art communications and outstanding laboratory, pharmacy, qualityassurance, data management and regulatory support. With its robust administrative framework,the UNC Global HIV CTU is optimally positioned to provide scientific leadership and clinicaltrials infrastructure to advance the field of agenda of the NIAID HIV networks and emerginginfectious disease such as the SARS-CoV-2 pandemic.",2020,2020,University of North Carolina at Chapel Hill,600000,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Impact/ effectiveness of control measures,2020 +C06679,3P30CA016056-43S3,Phase IbTrial of Rintatolimod and IFNa Regimen in Cancer Patients with Mild or Moderate COVID-19 infection,"Following infection with the novel coronavirus SARS-CoV-, immunocompromised and older individuals are at higher risk of severe illness and fatality. Patients with cancer exhibit multiple factors associated with elevated morbidity and mortality from COVID-19, including older age, pre-existing cardiac and lung disease, and immune impairment from the underlying malignancy and chemotherapy. While the innate immune response is the first line of antiviral defense against SARS-CoV-2, coronavirus infection is accompanied by suppression of type I interferon (IFN), thereby limiting activation of innate immune pathways required for immediate control of infection and adaptive immunity. Coronavirus-mediated inhibition of innate immunity via the type I IFN pathway allows the virus to replicate in epithelial cells, and particularly in high-risk patients, progress to pneumonia and respiratory failure. The mechanisms include inhibition of intracellular signaling driven by pattern recognition receptors (e.g. RIG-I and MDA5) and suppression of IRF-3, a transcriptional factor that induces the expression of type 1 interferons. Consequently, we hypothesize that augmentation of innate immunity during early mild or moderately severe infection might avert progression to respiratory failure and mortality. Rintatolimod, a selective dsRNA ligand of TLR3, has strong antiviral activity against multiple viruses including the coronavirus SARS-CoV-1 in vitro and in animal models. The combination of recombinant IFN (Intron-A) and rintatolimod is currently being evaluated in clinical trials developed by our group at Roswell Park (NCT03403634, NCT03599453, NCT03899987) for patients with multiple solid tumors. In this proposal, we will re-purpose these agents to test whether the synergistic combination therapy will overcome the defective ability to induce type I IFN and stimulate TLR-mediated immune activation to provide protection from viral infection. Patients with cancer and mild or moderate COVID-19 within the Roswell Park catchment area will be enrolled over 6 months. Roswell Park has been selected by New York State as a regional testing area for COVID-19. The principal endpoint is safety of rintatolimod and Intron-A. Secondary endpoints are: (i) progression of infection requiring hospitalization; (ii) respiratory failure requiring mechanical ventilation; and (iii) death within 30 days Biospecimens collected from all patients will be used for translational assays, including kinetics of 1) viral clearance from nasal swabs and serum; 2) circulating inflammatory mediators; and 3) immunophenotype of lymphocyte subsets. Overall significance: We will repurpose the combination of two antiviral agents, which showed safety and promising results in patients with advanced cancer, to stop viral replication and mitigate the risk of progression to severe COVID19 in patients with cancer and SARS-CoV-2 infection. We expect to establish the safety of rIFNα and Rintatolimod in patients with cancer and COVID-19 and create the foundation for a larger multi-center randomized trial to test efficacy.",2020,2024,Roswell Park Cancer Institute Corp,420500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,1997 +C06680,3U19AI110818-07S1,High-throughput CRISPR-based Diagnostic Assay for Coronaviruses and Other Respiratory Diseases,"This proposal is intended to develop novel clinical diagnostics for, and increase our understanding of, thediversity, evolution, and spread of the newly emerged SARS-related coronavirus 2 (SARS-CoV-2) and otherrespiratory disease-causing pathogens in the United States.Coronavirus Disease 2019 (COVID-19) is associated with mild to severe respiratory disease, which can befatal. The novel viral etiological agent was first identified in December 2019 in Wuhan City, Hubei Province,China following an outbreak of pneumonia in individuals associated with a seafood market, and has sincespread globally. Originally named ""2019 novel coronavirus"", the virus has since been renamed severe acuterespiratory syndrome-related coronavirus (SARS-CoV-2). As of 10 February 2020, this includes 40,554confirmed cases and 910 deaths within 25 countries1. There have been 12 confirmed cases of COVID-19 inthe United States2, one of which was identified in Boston, MA in an individual who recently returned fromChina3. As public health agencies continue to monitor, track, and attempt to control its spread, it is most crucialthat they are equipped with the most effective tools to detect SARS-CoV-2 and distinguish it from othercommon causes of similar respiratory illness.This proposal addresses the critical gap in clinical diagnostics amidst the quickly moving COVID-19 outbreakby advancing multiplexed and point of care tools for screening a large number of respiratory disease samplesin a public health lab setting. It builds upon the genomic disease surveillance aims of the Viral project withinour existing Genomic Centers for Infectious Disease (NIAID), but accounts for the increased costs based onthe scale of work related to outbreak response. The tools generated by this project specifically address aglaring need at the public health laboratory level and have the potential to accelerate their investigative abilitiesfor undiagnosed respiratory disease.",2020,2024,Broad Institute Inc,349995,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2014 +C06681,3R01AI120938-05S1,Unlocking the Potential of HIV-Infected Deceased Donors for Organ Transplantation,"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor proven therapy for those who develop COVID-19. Passive antibody (Ab) administration through transfusion of convalescent plasma may offer the best and only short- term strategy to confer immediate immunity to susceptible individuals. In the United States, convalescent plasma transfusions could potentially be used as a prophylaxis for those at high-risk or those showing early symptoms of SARS-CoV-2. The blood transfusion community has begun collecting convalescent plasma from individuals who have recovered from COVID-19. As part of this effort, the US Food and Drug Administration has set a target of a titer greater than 1:320 for the ideal convalescent plasma donor. However, in the US only 70% of recovered patients (at least 14 days symptom free) have had high viral titers meeting the FDA recommendation. It is unknown why some individuals have high titers and others do not. We propose that increased viral titers are associated with low Ab binding affinity and increased inflammation resulting from a `cytokine storm'. We hypothesize that individuals with low antibody titers have a strong neutralizing antibody response due to higher antibody binding avidity, past viral exposures, and a favorable inflammatory response making them suitable for effectively clearing SARS-CoV-2 viral infections. The proposed aims will utilize >120 recovered SARS-CoV-2 donors of plasma and peripheral blood mononuclear cells (PBMC). Our clinical team has already received FDA Investigational New Drug (IND) clearance (IND 19725) and IRB approval to begin collecting convalescent plasma from recovered donors. We have already screened >120 convalescent plasma donors and have access to demographic information. We propose the following aims: Aim 1: Evaluate total antibody repertoire and neutralizing antibody response in convalescent plasma donors. Aim 1b. Evaluate current or prior viral exposures effect on SARS- CoV-2 antibody titers. Aim 2: Characterize inflammatory environment of convalescent plasma donors comparing those with a high titer to those with low titer. Aim 3: Assess if SARS-CoV-2 infection and associated proinflammatory immune responses reactivate latent viral infections in convalescent plasma donors. Convalescent plasma, as well as future monoclonal Ab therapy, represent some of the few promising therapies for COVID-19, and it is critically important to fully understand how these protective antibodies develop and how the viral titer can be interpreted. These proposed studies will also aid in the development of assays to determine antibody avidity and affinity in convalescent patient plasma to be used for future transfusion treatments and future outbreaks.",2020,2021,Johns Hopkins University,166213,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management",2020 +C06682,3R44AI152854-01S1,A smartphone-based rapid point-of-care test for SARS-CoV-2 detection from respiratory samples,"Abstract: In this Emergency Supplemental project, Luminostics will leverage our de-risked and scale-ready CLIP platformto develop a rapid smartphone-based point-of-care (POC) diagnostic for the detection of SARS-CoV-2 antigensfrom respiratory specimens. Luminostics' CLIP technology enables high-sensitivity lateral flow immunoassays(LFAs) using proprietary ""nanophosphors"" in combination with consumer smartphone optics and advanced signalprocessing algorithms for readout. As there is an immediate need for validated tools for rapid POC detection ofactive COVID-19 disease, this project will expeditiously adapt CLIP technology for detection of SARS-CoV-2antigens. While nucleic acid amplification tests (NAATs) have high accuracy, they can take days to return aresult, increasing the potential for continued transmission. In addition, most NAATs must be processed in alaboratory setting using expensive equipment. POC tests approved under the FDA's emergency useauthorization (EUA) for COVID-19 also require the purchase of specialized equipment, limiting widespread use.Thus, this project will develop, validate, and obtain FDA EUA for CLIP-COVID, a rapid smartphone-based testfor the detection of active COVID-19 infection based on an ultrasensitive immunoassay for SARS-CoV-2antigens in respiratory samples, including remnant viral transport media (VTM), nasopharyngeal/nasal swabs,nasal aspirate, saliva, and sputum. When used as labels in LFAs, Luminostics' patented persistent luminescentinorganic nanophosphors enable orders-of-magnitude lower limits of detection (LODs)-and therefore higherclinical sensitivities-on the CLIP platform compared to traditional visually-read LFAs, using only a smartphone'soptics, paired with an inexpensive adapter and mobile app, for unambiguous readout. The assay will use high-affinity monoclonal antibodies (mAbs) specific to SARS-CoV-2 antigens as diagnostic reagents. The CLIPplatform has been previously optimized to detect bacterial and viral pathogens has returned-for our Chlamydiatest-a clinical sensitivity of ~90%, specificity of 99%, and room temperature-stability for >15 months, enablingthe easy transport, storage, and stockpiling of test kits. This project seeks to develop, validate, and obtain FDAEUA for a CLIP-COVID diagnostic test through the following aims: 1) Screening of a large number of mAbs forspecific binding to SARS-CoV-2 antigens and selection of 2-3 preferred sandwich mAb pairs; 2) Developmentand optimization of CLIP-COVID components, including assay design, buffer/conjugate chemistry, and otherancillary components; and 3) Analytical/clinical validation studies, manufacturing transfer, and EUA submission.The expected outcome of this project is an affordable, shelf-stable, rapid, user-friendly test for POC COVID-19detection with FDA EUA submission completed within 6 months of project initiation.",2020,2021,Luminostics Inc,718866,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06683,3P30CA046934-32S3,SARS-COV-2 Environmental Constraint Effects on Cancer Prevention and Management Outcomes,"The Univ. of Colorado Cancer Center (UCCC) will participate in a consortium with other NCI-designated cancer centers to conduct a cross-sectional study within their respective regional catchment area populations. The consortium is led by the Univ. of Alabama (UAB), Birmingham's O'Neal Comprehensive Cancer Center. The first aim of the consortium is to investigate whether the SARS-COV-2 pandemic has impacted individuals' behaviors known to be associated with the development or prevention of cancer malignancies such as tobacco use, alcohol consumption, and physical activity. We are interested in investigating whether constraints due to the pandemic such as social distancing, loss of employment, and mental health challenges have affected individuals' health behaviors differently due to their age, race/ethnicity, rural/urban residency, or socio-economic status. UCCC will survey 1,500 individuals who experience cancer disparities in our catchment (Colorado), including individuals of Hispanic descent, who live in poverty, and reside in rural or frontier counties. We will use the Univ. of Colo. Health Survey Registry (Registry) to draw a sub-sample of individuals from these populations in Colorado. The Registry is enrolled from respondents to the statewide Tobacco Attitudes and Behavior Survey (TABS) on Health, a crosssectional population survey conducted in Colorado. The second aim of the consortium is to investigate whether constraints associated with the pandemic impacted cancer patients and survivors' ability to receive cancer treatment, follow-up or surveillance procedures, treatment regimens as prescribed, participation clinical trials, and interventions to manage pain and treatment side-effects. We will investigate if the pandemic impacted these outcomes differently for patients based on differences in their demographic characteristics, type of cancer diagnosed and stage of diagnosis, as well as their treatment status (active treatment, posttreatment survivorship). Moreover, we are also interested in investigating whether the SARS-COV-2 pandemic negatively affected outcomes that are important to cancer patients (patient-centered outcomes) such as their social and emotional functioning, quality of life, coping, social support/connectedness, and financial hardship due to loss of employment or health insurance associated with the pandemic's constraints. In Colorado, we will leverage our collaboration with UCCC's Oncology Research Information Exchange Network (ORIEN)/Total Cancer Care study platform to field a survey to 1,000 cancer patients and survivors who have been previously consented at UCCC to be contacted for research purposes. Constructs measured will be examined using descriptive statistics, with focus on how specific groups differ. Geospatial information will be used to compare area-based measures (e.g., socioeconomic indicators) to individual-level measures. Multilevel modeling will be conducted to understand the relationship between demographic variables and cancer preventive and cancer management outcomes and how the relationship is moderated by the SARS-COV-2 pandemic.",2020,2022,University Of Colorado Denver,155500,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,1997 +C06684,3R34DA050341-01S2,4/6 Planning for the HEALthy Early Development Study,"Abstract: The Planning for the HEALthy Early Development Study will contribute to the design andrecommended protocol for a future large-scale, multi-site research study to prospectively examinehuman brain, cognitive, behavioral, social and emotional development of children beginningprenatally through ages 9-10, and to determine the impact of maternal pre- and postnatalsubstance use on short- and long-term development of children. The Planning Study will linkinvestigators across 6 research sites who have complementary experience and expertise in theareas that are essential to designing the study. Planning activities will be accomplished using acoordinated set of 10 Working Groups who will work collaboratively to design a sampling andrecruitment strategy for a future large-scale study, to identify and recommend strategies foraddressing the challenges to ethical recruitment and retention of vulnerable populations, and todevelop and test a common protocol for neuroimaging, infant and child assessments, exposureassessment, biospecimen collection, and integration of novel technologies. By the end of thePlanning Phase, the 6 Consortium sites will have produced and tested a recommended protocolfor the future multi-site study, and will have established feasibility of carrying out the study protocolat each of the 6 linked sites.",2020,2021,University Of California-San Diego,228033,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Indirect health impacts | Health service delivery | Institutional level capacity strengthening,2019 +C06685,3UG1DA049435-02S1,Greater Southern California Node of the Clinical Trials Network,"Project Summary/Abstract This application, responding to the Notice of Special Interest (NOSI) regarding the Availabilityof Administrative Supplements and Urgent Competitive Revisions for Research on the 2019 NovelCoronavirus (NOT-DA-20-047), requests an administrative supplement to the Rural Expansion ofMedication Treatment for Opioid Use Disorder (Rural MOUD, CTN-0102). The main purpose of theparent project is to investigate the impact of telemedicine (TM) on MOUD access and retention forindividuals with OUD in rural primary care settings. The coronavirus disease 2019 (COVID-19, orCOVID for short) pandemic has forced many health care systems to rapidly implement remote caremodels, which is of direct relevance to this project. Building upon the existing research plan, werequest an administrative supplement to conduct a thorough investigation of COVID's impact on TMpractices and access to MOUD in rural communities. In addition to characterizing changes inattitudes and perceptions regarding TM for OUD treatment, we will investigate and assess the impactof COVID over the next 2 years with regard to changes in MOUD access and services (especially TM)in rural primary care settings and in OUD patients' use of substances (particularly opioids) and healthconditions. Study specific aims include: Aim 1. To assess changes in MOUD access and services(especially TM) in rural primary care settings over the COVID pandemic, and Aim 2. To assesschanges in OUD patients' substance use (particularly opioids) and health conditions over the COVIDpandemic. The supplement funding will support (1) qualitative data collection and analysis thatincludes focus groups and semi-structured interviews to document COVID impact from theperspective of community stakeholders, providers, and patients drawn from primary care clinicsserving rural communities, and (2) quantitative data collection and analysis that includes healthrecords for patients served by the rural primary care clinics as well as self-report from OUD patients'participant surveys to investigate COVID impact on the use of healthcare, TM, and substances.Findings will contribute to scientific knowledge regarding COVID impact, responses, andconsequences in rural communities, as well as to inform and shape future development of remotecare models.",2020,2024,University of California-Los Angeles,120879,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C06686,3K01AI141579-02S1,"Hospital-Associated Respiratory Virus Infections: Molecular Epidemiology, Clinical Outcomes, and Cost-Effectiveness of Interventions - COVID-19 Administrative Supplement","PROJECT SUMMARY / Abstract: The COVID-19 pandemic has strained hospital capacity and led to shortages in personal protective equipmentand testing supplies. This is particularly concerning because the SARS-CoV-2 virus that causes COVID-19 hasresulted in notable healthcare associated outbreaks, as have other novel coronaviruses such as SARS andMERS. Past studies have shown that these outbreaks are preventable with prompt diagnosis of cases andappropriate use of personal protective equipment. In the face of shortages, hospitals must make rapiddecisions on strategies to room patients, assign infection control precautions, ration personal protectiveequipment, and maintain adequate staffing. Accurate data and projections are needed to inform thesedecisions and evaluating their success is critical to managing the ongoing outbreak and informing futureresponse. This need can be met by applying the existing aims of K01AI141579 to hospital-associated SARS-CoV-2 infection. The overall objective of the existing K01 project is to support Josh Petrie, PhD in thedevelopment of expertise in healthcare epidemiology, state-of-the-art molecular methods, and advancedmodeling techniques. Completion of this objective is in progress through focused training and careerdevelopment activities in healthcare epidemiology, next generation sequencing, bioinformatics, cost-effectiveness analysis, and mathematical modeling that is overseen by an excellent team of mentors. The skillsthat are being developed by the training and career development objectives are strengthened by mentoredresearch to accomplish the following Specific Aims: (1) Define the epidemiology and burden of community-acquired and hospital-associated respiratory virus infections and compare clinical impact by viral species; (2)Improve the sensitivity and specificity of case definitions to identify hospital-associated respiratory virus casesby integrating clinical, epidemiologic, and molecular data; and (3) Determine the cost-effectiveness ofincreased respiratory virus screening and expanded infection control measures to reduce HA-RVI usingmathematical models. The proposed administrative supplement will facilitate application of these aims tohospital-associated SARS-CoV-2 infection. The expected research outcomes of the proposed project are, 1)determination of the incidence and outcomes of hospital-associated SARS-CoV-2 infections; 2) improvedidentification of hospital-associated SARS-CoV-2 infections through integration of clinical, epidemiologic, andmolecular data; and 3) quantification of the effects of COVID-19 response strategies in the hospital on theincidence of hospital-associated SARS-CoV-2. The proposed research is significant because it is expected thatthe outcomes of this work and future studies that build upon it, will inform ongoing response to the COVID-19pandemic and future pandemics. This research is innovative both in its use of cross-disciplinary methodologythat allows for new avenues of research.",2020,2022,University Of Michigan At Ann Arbor,42992,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C06687,3R44AI118017-03S1,Hawaii Biotech COVID-19 Response to PA-18-591,"7. Project Summary/Abstract Coronaviruses have been identified in several avian hosts, as well as in various mammals, includingcamels, bats, palm civets, mice, dogs, and cats. Among the coronaviruses that are pathogenic to humans,most are associated with mild clinical symptoms. However, In the last 18 years there have now been 3significant coronavirus outbreaks that have greatly impacted global health. First, there was the SevereAcute Respiratory Syndrome (SARS) in 2002, then the Middle East Respiratory Syndrome (MERS) in 2012,and most recently a novel coronavirus in 2019, now officially named SARS-CoV-2 and the disease it causesin referred to as COVID-19. On March 11, 2020, as a result of the rapid global spread of the virus, the WHOdeclared that COVID-19 had reached pandemic levels. The emergence of the novel SARS-CoV-2necessitates the need to develop effective medical counter measures to effectively respond to the publichealth threat posed by this virus. Currently, there are at least 40 SARS-CoV-2 vaccine candidates indevelopment. These employ methods that include nucleic acid-based vaccines, viral vectored vaccines, VLPbased vaccines, and recombinant subunit vaccines. Our approach to develop a SARS-CoV-2 vaccine is touse an Administrate Supplement to the current SBIR Phase IIB grant (2R44AI118017-03), ""Cross-ProtectiveMultivalent Vaccine for Tick-Borne Flaviviruses."" The overall goal of this administrative supplement isto expand the scope of the current grant and leverage the use of the S2 cell vaccine platform toexpress recombinant subunits representing the SARS-CoV-2 spike protein and determine theirpotential as vaccine candidates. Subunits that represent the Spike (S) glycoprotein ectodomain(transmembrane region removed) and the S RBD will be expressed with and without trimerization domains.The biochemical and immunological characteristics of subunits will be determined. The evaluation ofimmune responses elicited by the SARS-CoV-2 recombinant subunits will include novel adjuvantformulations with different mechanisms of action in an effort to identify formulations that induce potent,protective immune responses, and support dose sparing, while avoiding Th2 biases immune responses.Formulations that provide the best immunogenic responses will be utilized to assess protective efficacy in atransgenic mouse model. In the development of coronavirus vaccines, it is important to carefully evaluatevaccine candidates in terms of safety as prior studies have identified concerns of enhanced disease as aresult of skewed antibody responses that result in inflammatory alveolar damage. Our studies are designedto address these concerns through the design of subunits and the use of adjuvants that engender balancedTh1/Th2, or Th1 biased responses. The proposed recombinant subunit approach provides a means todeliver a safe, stable, and established manufacturing platform for a SARS CoV-2 vaccine.",2020,2020,Hawaii Biotech Inc,389739,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C06688,3UL1TR002544-03S3,Tufts Clinical and Translational Science Institute,"PROJECT SUMMARY The ongoing COVID-19 pandemic is an urgent public health crisis with few if any rapid and practicalsolutions. From the time that severe acute respiratory syndrome (SARS) coronavirus 2, SARS-CoV-2, wasfirst reported there have been approximately 2.7 million cases worldwide, 900,000 of which occurred in theUnited States; resulting in nearly 50,000 American deaths to date. Given the seriousness and time-sensitivenature of this highly contagious virus, the medical and scientific communities must work quickly and efficientlyto find a feasible way to address this global emergency. While SARS-CoV-2-infected patients most commonly present with fever, tiredness and dry cough; asignificant subset of these patients present with gastrointestinal (GI) issues such as diarrhea, alluding to thepotentially understated role of SARS-CoV-2 in the intestine. A recent study found that fecal viral shedding cancontinue as long as 5 weeks after the last detection of SARS-CoV-2 RNA in respiratory samples, suggestingthat the GI tract serves as a viral reservoir and allows for prolonged COVID-19 infection and transmission.Given that SARS-CoV-2 is so highly contagious, can be easily spread by both respiratory droplets and fecal-oral route, and can be passed on by asymptomatic carriers, limiting its transmission is paramount to publichealth. There is a critical need to develop practical COVID-19 intervention strategies to treat SARS-CoV-2infection and to prevent person-to-person transmission. There are no current proven treatments for COVID-19, and significant efforts are going towarddeveloping novel therapeutics that have not been assessed for safety in humans. Repurposing reliable andeffective drugs for COVID-19 therapy is not only a safer strategy, but will also allow for more rapid introductioninto clinical practice. For this reason, we propose to use the widely used antihelmintic drug, Niclosamide (NIC),for treatment of COVID-19. FDA-approved NIC, is an oral medication used to treat tapeworm infestations,which is on the World Health Organization (WHO) List of Essential Medicines. NIC was found to inhibit SARS-CoV-2 in in vitro studies, and was also found to inhibit similarly structured RNA viruses both in vitro and in vivo.Its mechanism of action in this capacity is to increase the pH within acidic endosomes of host cells, therebyinhibiting virus entry and release. Importantly, NIC has also demonstrated anti-inflammatory activity, and hasbeen shown to function as a bronchodilator in animal studies. Our overall goal is to determine the potential of NIC as both a treatment early in the course of COVID-19 infection as well as a prophylactic measure to prevent spread of SARS-CoV-2 virus. As such, we propose toconduct a randomized, double-blind controlled clinical trial to evaluate the efficacy of NIC in shorteningcontagious period of COVID-19 as determined by time to viral clearance from both respiratory and fecalsamples, as well as its ability to mitigate clinical outcomes of the disease.",2020,2023,Tufts University Boston,1359953,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2018 +C06689,3UL1TR002243-04S2,Vanderbilt Institute for Clinical and Translational Research (VICTR),"The Vanderbilt Institute for Clinical and Translational Research (VICTR) is a highly functionaland integrated clinical and translational (C&T) research infrastructure that has raised the qualityand scientific rigor of the research conducted at Vanderbilt and longstanding partner Meharry,the nation's oldest historically black academic health science institution. VICTR will contribute tothe mission of the CTSA program while leveraging unique resources and expertise withinVICTR's Hub with these aims: 1) Leverage VICTR's strong collaborative energy to enhanceteam science methodologies that propel transdisciplinary research approaches, and integrateproven community engagement principles to stakeholders for all stages of research; 2) Develop,implement and disseminate informatics and data organization methods to promulgate researchefficiency, quality, and preparedness and integrate data collection in the conduct of pragmatictrials; 3) Ensure the translational science workforce is diverse and has the skills, knowledge,and resources necessary to advance translation of discoveries; 4) Measurably improve theefficiency, quality, and representativeness of C&T studies by enhancing and systematicallyintegrating services and programs that support highest quality research initiation and conduct;5) Measurably improve the efficiency and quality of multi-site clinical trials, in collaboration withthe TICs and RICs, by leveraging centralized regulatory and legal agreements, providing rapidfeasibility and recruitment methods and practices, and creating and disseminating novel clinicaltrial designs and methodologies; and 6) Utilize unique strengths leveraging novel resourcesBioVU and PheWAS to guide drug development and repurposing.",2020,2021,Vanderbilt University Medical Center,96461,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,Data Management and Data Sharing,,,United States of America,,,,2020 +C06690,3R44GM132796-03S1,Rapid Hit Generation and Lead Elaboration for SARS-CoV-2 Therapeutics,"The novel SARS coronavirus (SARS-CoV-2) global pandemic has taken a strong foothold and itis estimated that it will infect hundreds of millions of people, with millions dying. These estimatesunderscore the severity of the COVID-19 disease, caused by SARS-CoV-2, yet there are currentlyno effective treatments that can be administered to infected individuals. Our approach centeredaround a proprietary structure-based drug discovery engine, which combines rapid screening ofa molecular fragment library in a fragment-based drug discovery approach with high-throughputX-ray crystallography. We will discover and develop novel small molecule inhibitors of the receptorbinding domain (RBD) of the SARS-CoV-2 viral spike protein S1 subunit (attachment inhibitors),inhibitors of the viral spike protein S2 subunit (fusion inhibitors), and the Nsp14-Nsp10 complex(replication mismatch repair inhibitors). Our approach resolves an important step in early drugdiscovery, i.e., the generation of reliable, high-quality, target-specific hits that can be advanced totherapeutics development. Our method provides experimental validation and unprecedentedability to visualize 3D protein-ligand interactions in a single step, delivering valuable actionableassets (identification and definition of binding sites and binding pose) for immediate chemistryand biology follow up in early drug discovery. Our goal is to target conserved amino acid residueswithin these proteins to discover and advance molecules that may inhibit the SARS-CoV-2proteins and also serve as pan-coronavirus inhibitors. Thus we will create broad-spectrumantiviral therapeutics against multiple coronavirus strains and against the homologous proteins inSARS and MERS, thereby effectively creating treatments for both current and future coronavirusoutbreaks. We will determine X-ray crystal structures of the SARS-CoV-2 RBD, S2 and Nsp14-Nsp10 proteins bound to molecular fragments and elaborate these fragment hits into inhibitorsthrough a combination of computational and medicinal chemistry, high-throughput structuralbiology, and biophysical assays.",2020,2021,Accelero Biostructures Inc,486536,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2016 +C06691,3UG1DA049467-02S1,Great Lakes Node of the Drug Abuse Clinical Trials Network,"PROJECT SUMMARY Individuals with substance use disorders are disproportionately experiencing homelessness, poverty,and chronic medical conditions (diabetes and hypertension), which are emerging risk factors for contractingSARS-CoV-2 (official name for the virus that causes COVID-19). Different types of substance use have beenassociated with development of respiratory infections and progression to severe respiratory failure, also knownas Acute Respiratory Distress Syndrome (ARDS). However, complex syndromes like ARDS and behavioralconditions like substance misuse are difficult to identify from the electronic health record. Clinical notes andradiology reports provide a rich source of information that may be used to identify cases of substance misuseand ARDS. This information is routinely recorded during hospital care, and automated, data-driven solutionswith natural language processing (NLP) can extract semantics and important risk factors from the unstructureddata of clinical notes. The computational methods of NLP derive meaning from clinical notes, from whichmachine learning can predict risk factors for patients leaving AMA or progressing to respiratory failure. Ourteam developed tools with >80% sensitivity/specificity to identify individual types of substance misuse usingNLP with machine learning (ML). Our single-center models delineated risk factors embedded in the notes (e.g.,mental health conditions, socioeconomic indicators). Further, we have developed and externally validated amachine learning tool to identify cases of ARDS with high accuracy for early treatment. We aim to expand thiswork by pooling data across health systems and build a generalizable and comprehensive classifier thatcaptures multiple types of substance misuse for use in risk stratification and prognostication during the COVIDpandemic. We hypothesize that a single-model NLP substance misuse classifier will provide a standardized,interoperable, and accurate approach for universal analysis of hospitalized patients, and that such informationcan be used to identify those at risk for disrupted care and those at risk for respiratory failure. We aim to trainand test our substance misuse classifiers at Rush in a retrospective dataset of over 60,000 hospitalizationsthat have been manually screened with the universal screen, AUDIT, and DAST. This AdministrativeSupplement will allow us to examine the correlations between substances of misuse and risk for COVID-19 aswell as development of Acute Respiratory Distress Syndrome (ARDS) in the context of these phenomena.",2020,2024,Rush University Medical Center,139752,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Epidemiological studies | Health Systems Research,Disease susceptibility | Health information systems,2019 +C06692,3UL1TR003096-02S3,2) Center for Clinical and Translational Science,"The COVID-19 global emergency raises many difficult patient care and healthcare management questions.Which drugs are the most viable candidates for a given patient? How can we efficiently and effectivelyassemble the right cohort for a trial? What social determinants impact course and outcome? How can werapidly deploy clinical decision support tools when new knowledge is available every day?The N3C is a partnership across the Centers for Translational Science Award (CTSA) hubs, several HHSagencies, distributed clinical data networks (PCORnet, OHDSI, ACT/i2b2, TriNetX), and other partnerorganizations. The N3C aims to improve the efficiency and accessibility of analyses with COVID-19 clinicaldata, expand our ability to analyze and understand COVID, and demonstrate a novel approach forcollaborative pandemic data sharing.Under this proposal we will contribute electronic health record data on patients afflicted with COVID-19 andappropriate control patients. We will also participate in three workstreams: (a) Phenotype and Data Acquisition(brining our extensive experience with development of patient registries and data repositories), (b) DataIngestion and Harmonization (contributing our experience with harmonizing and terminologies for UAB,Columbia University, the NIH's Biomedical Translational Research Information System (BTRIS) and the UnifiedMedical Language System), and (c) Collaborative Analytics (with experience in developing collaborativeplatforms for team-based translational science and analytics for precision medicine).",2020,2021,University Of Alabama At Birmingham,148500,Human Populations | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2020 +C06693,3R01AI146779-02S1,Epitope focusing to the receptor binding motif for a universal coronavirus vaccine,"Project Summary: There is urgent need for the development of effective countermeasures against the newly emerged novelcoronavirus or ""nCoV"" (also known as COVID-19). The development of a ""universal"" coronavirus (CoV)vaccine would not only be effective against COVID-19 but, in theory, would protect against future,potential pandemic CoV strains. The pathway to such a vaccine will likely focus on the design of novelimmunogens that elicit broadly neutralizing antibodies to conserved viral epitopes, such as the receptorbinding site (RBS). Here we leverage our structure-based, ""resurfacing"" and glycan engineeringimmunogen design approaches for a universal influenza vaccine and extend it to COVID-19. Our ongoingstudies for influenza demonstrate that our resurfaced, heterochimeric immunogen approach substantiallyincreased the overall frequency of elicited RBS-directed responses and our glycan engineering approachcould effectively focus the immune response to a novel, conserved influenza hemagglutinin epitope; weenvision that implementing comparable immunogen design approaches for COVID-19 specificallyfocusing to its receptor-binding interface epitope would yield similar results. We intend to use thisAdministrative Supplement to generate preliminary data to show the efficacy of our approach for aCOVID-19 vaccine, and to optimize the vaccine regimen in the murine model; the data generated herewill form the basis for future studies for a universal CoV vaccine.",2020,2022,Massachusetts General Hospital,390265,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2019 +C06694,3U24GM132013-02S1,Accelerating COVID-19 modeling research by improving the discovery and new use of data: leveraging community engagement and automation of curation workflows,"Project Summary: The Models of Infectious Disease Agent Study (MIDAS) research network has been highly productive, and akey challenge faced by the MIDAS and the general scientific community is how to make its models anddatasets accessible to others so as to amplify and accelerate the research and discovery process. The value ofdata and software as research products has been widely acknowledged, but individual researchers can facepersistent barriers to data sharing, including the prevailing ""publish or perish"" paradigm as the main driver foracademic tenure and promotion. While new technology can enable data sharing, a social-cultural, human-based approach is essential to improve data access and reuse in a community. We propose to create aMIDAS Coordinating Center (MCC) that is investigator-focused, with the long-term goal of increasingthe use of MIDAS research products for new research and discovery. Our approach will follow FAIR DataPrinciples developed by the NIH Data Commons Consortium to specify requirements for Findable, Accessible,Interoperable, and Reusable research products. We will leverage FAIR-enabling technology developed by theInformatics Services Group (the current MIDAS Information Technology Resource) and add community-basedresearch, outreach, education, and governance. We propose the following specific aims: (1) Facilitatecompliance of MIDAS datasets and software with FAIR Data Principles; (2) Create FAIR 'gold standarddatasets' (GSD) to improve testing of MIDAS models; (3) Create a dynamic infrastructure and support servicesfor data storage and high-performance computing; (4) Coordinate outreach through an annual network meetingand improved electronic communication channels; (5) Educate MIDAS trainees in open science and researchdesign principles; and (6) Create executable workflow representations of MIDAS models to improve modeltesting and reproducibility. The MCC will augment the impact of NIGMS investments in basic scientificresearch by improving the use of MIDAS research products. Other scientists or computer algorithms will beable to discover, access, and integrate MIDAS products and increasingly, machine-driven access to, and useof, datasets and software will accelerate the rate of new discoveries and innovation for control of infectiousdisease threats. The MCC will be led by Dr. Wilbert van Panhuis, MD, PhD, who has worked asepidemiological modeler in the Pitt MIDAS Center of Excellence, and who has collaborated as data scientistwith the ISG. Dr. Van Panhuis has a unique track record of unlocking access to valuable datasets previouslyunavailable to MIDAS and a proven ability to design, and successfully lead, large-scale internationalcollaborations. As PI of the MCC Dr. Van Panhuis will proactively collaborate with MIDAS investigators and theMIDAS Steering Committee. The other MCC team members are also firmly rooted into the MIDAS communityand have complementary expertise in infectious disease and data science.",2020,2024,University Of Pittsburgh At Pittsburgh,334466,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,Data Management and Data Sharing,,,United States of America,,"Policies for public health, disease control & community resilience",Community engagement,2019 +C06695,3R01EB028628-01S1,A rapid and inexpensive point of care diagnostic for SARS-CoV-2 infection,"Project Summary: The project outlines our plans to develop a rapid, point-of-care diagnostic test for the novel SARS-CoV-2 virus that can be used in resource-limited locations. The foundation of the project is a highly selective chemiluminescent reporter probe that produces light when activated by the major viral protease SARS-CoV-2 Mpro. This approach will enable rapid testing (<30 min) of easily obtained clinical samples (i.e., saliva) using a detector that has limited power needs and that can interface with standard smart phones to provide a diagnosis.",2020,2021,Stanford University,354825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06696,3U24GM132013-02S2,COVID-19 Modeling Urgent Grant Program for the Modeling of Infectious Disease Agent Study,"Project Summary: The Models of Infectious Disease Agent Study (MIDAS) research network has been highly productive, and akey challenge faced by the MIDAS and the general scientific community is how to make its models anddatasets accessible to others so as to amplify and accelerate the research and discovery process. The value ofdata and software as research products has been widely acknowledged, but individual researchers can facepersistent barriers to data sharing, including the prevailing ""publish or perish"" paradigm as the main driver foracademic tenure and promotion. While new technology can enable data sharing, a social-cultural, human-based approach is essential to improve data access and reuse in a community. We propose to create aMIDAS Coordinating Center (MCC) that is investigator-focused, with the long-term goal of increasingthe use of MIDAS research products for new research and discovery. Our approach will follow FAIR DataPrinciples developed by the NIH Data Commons Consortium to specify requirements for Findable, Accessible,Interoperable, and Reusable research products. We will leverage FAIR-enabling technology developed by theInformatics Services Group (the current MIDAS Information Technology Resource) and add community-basedresearch, outreach, education, and governance. We propose the following specific aims: (1) Facilitatecompliance of MIDAS datasets and software with FAIR Data Principles; (2) Create FAIR 'gold standarddatasets' (GSD) to improve testing of MIDAS models; (3) Create a dynamic infrastructure and support servicesfor data storage and high-performance computing; (4) Coordinate outreach through an annual network meetingand improved electronic communication channels; (5) Educate MIDAS trainees in open science and researchdesign principles; and (6) Create executable workflow representations of MIDAS models to improve modeltesting and reproducibility. The MCC will augment the impact of NIGMS investments in basic scientificresearch by improving the use of MIDAS research products. Other scientists or computer algorithms will beable to discover, access, and integrate MIDAS products and increasingly, machine-driven access to, and useof, datasets and software will accelerate the rate of new discoveries and innovation for control of infectiousdisease threats. The MCC will be led by Dr. Wilbert van Panhuis, MD, PhD, who has worked asepidemiological modeler in the Pitt MIDAS Center of Excellence, and who has collaborated as data scientistwith the ISG. Dr. Van Panhuis has a unique track record of unlocking access to valuable datasets previouslyunavailable to MIDAS and a proven ability to design, and successfully lead, large-scale internationalcollaborations. As PI of the MCC Dr. Van Panhuis will proactively collaborate with MIDAS investigators and theMIDAS Steering Committee. The other MCC team members are also firmly rooted into the MIDAS communityand have complementary expertise in infectious disease and data science.",2020,2024,University Of Pittsburgh At Pittsburgh,1098999,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Health Systems Research,Health information systems,2019 +C06697,3P30CA036727-33S1,COVID-19 Antigen Team for Immunotherapy and Monitoring Patient Immune Response,"Coronaviruses (CoVs) are one of the major viral pathogens that primarily target the human respiratorysystem. Previous outbreaks include the severe acute respiratory syndrome (SARS)-CoV and theMiddle East respiratory syndrome (MERS)-CoV which were characterized as agents that are a greatpublic health threat. In December 2019, the novel SARS-CoV-2 that causes COVID-19 emerged tobecome a worldwide pandemic. By April 10th, 2020 COVID-19 caused serious illness in more than 1.7million individuals and more than 100,000 deaths (https://www.worldometers.info/coronavirus/).Furthermore, it is noteworthy that immunocompromised individuals, such as cancer patients, areparticularly vulnerable to COVID-19. There is currently no specific drug or vaccine to treat the COVID-19 infection, only supportive care is being given to the infected individuals around the world.The speed with which the current COVID-19 pandemic has expanded across the globe underscoresthe urgent need to develop a rapid-response capability to produce anti-viral therapies that couldmitigate the impact of this disease, as well as future diseases1. To address this need, the University ofNebraska Medical Center (UNMC) and SAb Biotherapeutics (SAb) propose to utilize transchromosomicbovine (Tc bovine) technology to rapidly produce human anti-SARS-CoV-2 polyclonal IgG antibodiesfor use as an immunotherapeutic for COVID-19 patients. The basis of this approach is the unique Tcbovine technology in which the genes encoding the IgG antibodies produced by these animals arereplaced with their human counterparts. Thus, the vaccination of these animals with antigen results inthe large-scale production of antigen-specific human polyclonal antibodies directed to that antigen. Torapidly develop such polyclonal antibodies, our COVID-19 antigen team is producing purified SARSCoV-2 antigens for vaccinations to generate highly specific human polyclonal antibodies that will thenbe purified and used for therapeutic and/or prophylactic purposes in the fight against COVID-19. Ourapproach is similar to the use of convalescent serum from patients who have recovered from COVID-19 to treat active cases of the disease2-4 but our approach will be more powerful in that it can beeffectively applied broadly to a large patient population. Importantly, this approach has already provensuccessful in preventing MERS-CoV5 and Ebola6 in animal studies. In fact, SAb has already put ahuman anti-MERS-CoV polyclonal antibody product through Phase 1 clinical trials7. It is noteworthythat during the Ebola outbreak researchers observed in survivors early and increasing levels of IgGdirected against the nucleoprotein, and other viral proteins, not against the surface glycoprotein8,9.Therefore our approach includes several SARS-CoV-2 antigens as well as the spike surfaceglycoprotein. Once the human polyclonal Abs are generated, UNMC will conduct in vitro and in vivoefficacy studies and will seek FDA approval to clinically evaluate the immunotherapeutic in humans atthe UNMC biocontainment facility.",2020,2021,University Of Nebraska Medical Center,381250,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,1997 +C06698,3K24AI150991-01S1,Impact of Heterogeneous Airway Epithelial ACE2 Expression and Interferon Responses on SARS-CoV2 Infectivity and Replication,"Project Summary: This application is an Emergency Competitive Revision (PA-20-135) to existing NIH award K24AI150991proposing immediate work to help address the urgent need for research on Severe Acute RespiratorySyndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19). While the majority ofcases of COVID19 result in mild symptoms, some progress to respiratory and multi-organ failure. The casefatality rate for COVID19 varies widely according to age group and underlying medical comorbidities. There anurgent need to improve our understanding of mechanisms that underlie the heterogeneity of disease severitywith SARS-CoV2 infection between individuals and explain why children are more resistant to developingsevere COVID-19 than adults. Such knowledge will be critical in developing novel therapeutic interventions totreat and prevent SARS-CoV2 infection and COVID19 disease. One theory for the widely varying COVID-19disease severity between children and adults, and even between older adults, is heterogeneity betweenindividuals in how the virus gains entry to airway epithelial cells (AECs). The spike protein of SARS CoV2 usesangiotensin converting enzyme 2 (ACE-2) as its cell binding site and the membrane serine protease TMPRSS2primes the spike protein. In humans it is unknown if epithelial expression of ACE-2 or TMPRSS2 are loweramong children as compared to adults. In animals two common antihypertension medications (angiotensin IIreceptor blockers, ARBs; and angiotensin-converting-enzyme inhibitors, AECi) increase ACE-2 expression,fueling debate about the effect of these drugs on the infectivity of SARS-CoV2 and risk of COVID-19. Werecently observed that ACE-2 expression by bronchial AECs from children increases following infection withhuman rhinovirus, prompting us to question whether a recent rhinovirus infection modulates SARS-CoV2infection and the risk of COVID-19. The first aim of this Competitive Revision is to determine whether bronchialAEC expression of ACE-2 varies with age or pre-infection with human rhinovirus, and whether treatment ofAECs with ARBs, ACEi or exogenous ACE-2, modulate SARS CoV2 infectivity and replication. A secondpotential explanation for varying COVID-19 disease severity is heterogeneity in type I and III interferon (IFNI/III) responses between individuals to SARS-CoV2. The second aim of this Competitive Revision, whichlogically extends from the goals of the applicant's parent award (K24AI150991), is to determine if heterogeneityof AEC IFN I/III responses following SARS-CoV2 infection of primary AECs from children and adults isassociated with viral replication, and whether the drug azithromycin increases AEC IFN I/III responses toSARS-CoV2 and reduces viral replication. Finally, this supplement to K24AI150991 will also support the directmentorship of 3 junior faculty physician-scientists and a PhD candidate who are all engaged in mechanisticCOVID-19 patient-oriented research under the applicant's mentorship or co-mentorship.",2020,2022,Seattle Children'S Hospital,193352,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06700,3P20GM103629-09S1,Predictive Modeling of COVID-19 Progression in Older Patients,"The objective of this proposal is to develop a predictive model to identify individuals who are infected withSARS-CoV-2 and at risk of developing severe COVID-19. Louisiana has the 5th highest death rate per capita inthe United States as of May 4th, 2020. Severe disease is seen in older individuals and those with underlyingconditions. The New Orleans population is particularly susceptible to severe COVID-19 as hypertension,diabetes and obesity are rampant. After infection, acute lung injury caused by the virus must be repaired toregain lung function and avoid acute respiratory distress syndrome and pulmonary fibrosis. Mounting evidencesuggests that patients with severe COVID-19 have cytokine storm syndrome, which may exacerbatemultiorgan injury and risk of fibrotic complications. Lack of effective ways to identify and attenuate severeCOVID-19 progression persist due to limited understanding of the biological pathways responsible for cytokinestorm syndrome and increased risk in older patients. Therefore, there is a need to determine the criticalcytokine profiles responsible for severe COVID-19 progression to develop effective treatments. Further, it isessential to find a way to stage disease trajectory(ies) to identify therapeutic targets with precision to attenuatedisease progression and uncover preventive strategies. Towards this end, we seek to leverage a mathematicalmodel of SARS-CoV-2-induced lung damage to predict severity of acute respiratory distress syndrome andpulmonary fibrosis by considering key cytokine-cell interactions. We hypothesize that the model will accuratelypredict quantitative changes in suites of key cytokines and matrix accumulation with varying COVID-19progression within 10% accuracy. To accomplish this, we have assembled an investigative team at TulaneUniversity with key expertise in virology, clinical infectious disease research, bioinformatics, and predictivemathematical models of tissue remodeling. In Aim 1 of the proposal, we will identify the critical cytokinemarkers linked to viral-induced lung damage and pulmonary fibrosis. This will be accomplished by leveragingmachine learning to determine the biomarkers and molecular pathways characterizing progression of severeCOVID-19 to focus model formulation. In Aim 2, we will predict the severity of COVID-19 in older patients.Model predictions will be compared to blood markers of COVID-19 disease in cohorts of older patients atdifferent stages of disease progression. The model will be refined and informed by cytokine data to discerncausal biological pathways and disease processes that can be tested and targeted. Our expected outcome isto have determined the critical cytokine interactions responsible for lung tissue damage and dictating pathwaysfor varying disease trajectories in older patients. These results are expected to have an important impact asthe proposed predictive model will open new avenues of research to rationally design pharmaceuticalinterventions for severe COVID-19 patients. Specifically, the study will provide a paradigm-shifting open-sourcetool to delineate target therapeutics, estimate their efficacy, and move towards development of patient-specifictreatment plans for older individuals.",2020,2022,Tulane University Of Louisiana,379884,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2012 +C06701,3U45ES006172-28S1,Coronavirus and Infectious Disease Response Training,"Program Summary/Abstract: This is a supplemental proposal for a coronavirus and infectious disease response training program to beimplemented by The New England Consortium-Civil Service Employees Association (TNEC-CSEA), apartnership between the University of Massachusetts Lowell (UML), four New England coalitions foroccupational safety and health (COSH groups) in Massachusetts, Rhode Island, Connecticut, and NewHampshire, and CSEA, Local 1000 AFSCME, in New York. Since 1987, TNEC has been providing participatoryhands-on HAZWOPER training to workers throughout the New England region. In addition to HAZWOPERtraining, the COSH organizations provide a diversified set of health and safety training programs for laborunions, community organizations, school personnel, and other groups and individuals. CSEA represents300,000 public sector workers in New York State and has been part of AFSCME's NIEHS WTP-awardedtraining program since 2003 and provided substantial direct training from 2007 until joining TNEC. CSEA hasbuilt effective internal health and safety management systems through site-specific hands-on training and usesa labor-management cooperative peer-trainer model with 150 active Peer Trainers, 24 of which have beeninvolved for ten or more years, and part of the Emergency Management Operations Protocol to be deployed inemergencies and disasters. TNEC/New England's previous experience in infectious disease training includes:in 2008-09, delivery of seven 6 to 7 hour Train-the-Trainer courses on avian flu pandemic preparedness toMassachusetts public school teachers, who then delivered training back in their school districts; and in 2014,delivery of Ebola-related training to 190 workers including employees of the New Hampshire Department ofPublic Health, members of the Massachusetts State Police, and for leaders of the Massachusetts NursesAssociation. Altogether, TNEC will deliver 29 courses for 1,010 students for 2,920 contact hours in NewEngland. CSEA will complete approximately 145 sessions for 1,142 participants for 1,376 contact hours in NewYork of mostly interactive online coronavirus/COVID-19 and infectious disease response training. Thesetrainings will include: overview of the SARS-CoV-2 virus; workers' rights; assessing exposure; prevention in theworkplace; personal protective equipment; keeping yourself safe; cleaning & disinfecting and returning towork; hazard communication/Safety Data Sheets; PPE for cleaning & disinfecting; cleaning & disinfectingdelivery systems; and mental health well-being. Our target populations are: 4,831,010 essential personnel inthe six New England states and 300,000 frontline workers in the public sector within New York state. TNEC-CSEA seeks to build sustainable capacity for CSEA peer trainers and TNEC/New England trainers to deliverongoing COVID-19 and infectious disease response trainings that will reduce exposures and increase thecapacity of employers and workers to identify and mitigate the occupational risk factors caused by COVID-19and infectious diseases with a focus on reaching vulnerable populations.",2020,2020,University Of Massachusetts Lowell,131566,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening,2020 +C06702,3R44ES028142-03S1,Just-In-Time Essential Worker COVID-19 Mobile Awareness Campaign,"Summary/Abstract. Just-In-Time Essential Worker COVID-19 Mobile Awareness CampaignThe objective of this effort is to improve essential worker safety through a just-in-time COVID-19 awareness trainingcampaign. The campaign will push brief (under three minute) modules of interactive multimedia, tailored to the specificjob of the worker, to the mobile devices of over 5,000 essential workers, track worker adoption of recommendedbehaviors, and adapt campaign enrollment protocols and training multimedia in response to worker behavior.Under the existing NIEHS WTP SBIR Phase II project, Cell Podium has started development of software that will managethe just-in-time and deliver the mobile multimedia modules. The software works through a cell phone's browser, doesnot require participants to download any mobile app, and the campaign is free to the worker and his/her employer.Content will consist of 10 to 20 brief (under three minute) modules that are specific to the specific job of the worker,delivered over a three week time frame, and derived from vetted training material posted by NIEHS and CDC. Apartnership with Rutgers School of Public Health Center for Public Health Workforce Development will ensure thequality of content and instructional design of the campaigns. The worker will be engaged with checklists, quizzes andopportunities for open-ended feedback, all which provide the campaign with formative and needs assessment withwhich to refine the campaign, and information on the worker's compliance with coronavirus safety recommendations.The just-in-time nature of the campaign supports not only its use as an unobtrusive job aid, but also supports multipleopportunities to revise the campaign itself to improve effectiveness.In response to the urgency of the coronavirus pandemic, project management will proactively recruit workers to thecampaign. The New Jersey Manufacturing Extension Program and the Urban League of Essex County will directly recruitthe workers of their constituents, which include diverse industries and vulnerable populations in New Jersey. Theseorganization will contact manufacturing companies or workers directly to encourage registration in the application. Nopayment is required from workers, and the registration process is simple. As part of formative assessment, reminderswill be sent to encourage participation to any worker who falls behind in the campaign. The outreach to workers is notlimited to the audience of these partner organizations. All organizations, including companies in the business incubatorof the New Jersey Institute of Technology (Newark, NJ), will also be encouraged to participate.",2020,2021,Cell Podium,200000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience | Research on Capacity Strengthening","Barriers, PPE, environmental, animal and vector control measures | Communication | Systemic/environmental components of capacity strengthening",2020 +C06703,3P30DA027828-10S1,Center for Prevention Implementation Methodology for Drug Abuse and HIV (Ce-PIM),"Abstract: This administrative supplement to the NIDA funded Center for PreventionImplementation Methodology for Drug Abuse and HIV is submitted to address theurgent crises in delivering evidence-based interventions for preventing the spread ofHIV and preventing opioid related deaths due to the policies and practices now beingundertaken in immediate response to the COVID-19 pandemic. Because there is suchlimited research to draw upon in this crisis, we need to rely on innovative modelingapproaches that build on Ce-PIM's existing work, as we expand to meet the newchallenges addressed by local governmental agencies and service delivery systems.We are partnering formally in this application with the Pinellas County Opioid TaskForce, which includes the county's Health Department, Human Services, OperationPAR and the University of South Florida. We will adapt two existing agent-basedmodels/ decision support tools to provide decision support to local governmental andsystem leaders on optimizing a set of interventions to reduce HIV spread and opioidrelated deaths in Pinellas County where these systems have been heavily impacted byCOVID-19. These models are built alongside the Task Force and emphasize theimpact on vulnerable populations, including the homeless, and on delivery ofmedications for opioid use disorder.",2020,2021,Northwestern University At Chicago,171041,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2011 +C06704,3P30CA016359-40S4,Isolation and profiling of antibodies targeting SARS-CoV-2,"A promising therapeutic and prophylactic strategy against COVID-19 is passive immunization through the transfer of anti-SARS-CoV-2 neutralizing antibodies and convalescent serum. However, there is growing evidence that antibody responses to the virus can also directly contribute to lethal immunopathology and hyperinflammation present in severe COVID-19 disease. Understanding the distinct mechanisms whereby humoral responses to SARS-CoV-2 provide protective antiviral immunity versus harmful immunopathology is thus essential in developing effective treatments for COVID-19. Furthermore, analysis of antibody responses in SARS-CoV-2-infected individuals will inform development of effective SARS-CoV-2 vaccines and reliable serological tests in the immediate future. Here, we propose to identify and characterize COVID19 patients' anti-SARS-CoV-2 antibodies and the epitopes on SARS-CoV-2 that are targeted by immune responses. The goals of the proposed research are to identify potent neutralizing antibodies against SARSCoV-2 that can be advanced as therapeutic drug candidates and elucidate potential roles for deleterious autoreactive cross-reactivity of humoral responses to the virus. Our working hypothesis is that anti-SARSCoV-2 antibody responses generate neutralizing protective antibodies in most subjects, whereas S1 spike protein-reactive antibodies may cross-react with self-antigens expressed on lung epithelial cells in patients severely affected by the virus as suggested by a previous SARS-Cov study. We therefore propose to isolate and produce in vitro anti-SARS-CoV-2-reactive neutralizing recombinant antibodies cloned from memory B cells and plasmablasts from the blood of patients and asymptomatic infected subjects. We will profile cloned recombinant antibodies and COVID-19 patient plasma samples for reactivity against a large panel of conformational SARS-CoV-2 antigens as well as extracellular/secreted human proteins to identify humoral responses that may contribute to viral clearance and COVID-19 immunopathology, respectively. Responses to extracellular SARS-CoV-2 antigens will be determined using a multiplex flow-cytometry based assay that enables simultaneous quantification of humoral responses against multiple viral proteins as well as a qualitative assessment of their ability to block the interaction of SARS-CoV-2 spike protein with its entry receptor ACE2. Potential autoreactive responses elicited by SARS-CoV-2 infection will be assessed using a technique called REAP (Rapid Extracellular Antibody Profiling), in which serum/antibodies are panned against a comprehensive library of >3,000 human extracellular proteins displayed on the surface of yeast. These studies will thus provide insight into the development of immune responses targeting SARS-CoV-2, identify potent neutralizing antibodies against SARS-CoV-2 that can be advanced as therapeutic drug candidates and may suggest therapeutic strategies to attenuate potentially pathogenic antibody responses.",2020,2023,Yale University,327490,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,1997 +C06705,3P30CA196521-05S2,Identifying immune correlates of disease severity and novel immune drivers of pathogenicity to target in patients with COVID-19,"There is a highly heterogeneous response to infection with SARS-CoV-2 with reports to date suggesting the vast majority of patients are minimally symptomatic, while a significant subset developing life-threatening lung injury associated with hyper-inflammatory response. While initial studies suggested that the cytokine storm was the main driver of lung injuries, more recent observation suggest that vascular lesions leading to severe vasculitis and disseminated intravascular coagulation may also significantly contribute to COVID-19 disease pathophysiology. Regardless of whether the hyperinflammation is causative or reactive, given much of the morbidity and mortality is also associated with hyperinflammation, a better understanding of the immunologic underpinnings of differential responsiveness is necessary to better identify therapeutic targets. Dozens of immunomodulatory agents are rapidly going into clinical trials as well as being used routinely, without a thorough understanding for which inflammatory pathways and cell types to best target, which could be detrimental to critically ill patients. Many of these agents are being tested within the Mount Sinai Health System in New York, a city disproportionately affected by COVID-19. We propose to focus the significant resources of our Human Immune Monitoring Center (HIMC) and the Mount Sinai Cancer Immune Monitoring and Analysis Centers (CIMAC), which have well established and validated platforms to characterize to an unprecedented depth the immune phenotype of SARS-CoV-2 patients at diagnosis and during disease progression with the overarching goal to establish an algorithm to predict disease severity and guide immunomodulatory strategies as well as identify novel immune targets of disease.",2020,2020,Icahn School Of Medicine At Mount Sinai,423750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2015 +C06706,3R43ES030582-01S1,Preventing Opioid Exposure Training (POET) for First Responders,"PROJECT SUMMARY/Abstract: In this competitive revision Phase I SBIR, Gryphon Scientific proposes to expand the scope of theongoing project to support the urgent need to develop and deploy training for first responderpopulations at risk of exposure to the novel coronavirus (COVID-19). The ongoing Phase I SBIRproject focuses on training first responders (including law enforcement, fire, and EMS personnel) torecognize and manage the risks of occupational opioid exposures. The training video format waschosen following formative research interviews with first responders, which revealed a clearpreference for training that could be administered to groups during short stand-up briefings. Currently,training content specifically includes topics such as routes of opioid exposure, PPE, situationalawareness, and recognizing and responding to exposure events. In this supplemental application,Gryphon proposes to expand the scope of the study by developing similar training videos on topicsrelated to the transmission of respiratory diseases, primarily focused on COVID-19. Specific topicsmay include pathogen fundamentals, transmission routes, and recommended measures to managerisk, including distancing measures when feasible, and the selection of appropriate personalprotective equipment (PPE) for various situations, including those where shortages preclude the useof recommended PPE. Recognizing the urgent need to deploy this training to the first respondercommunity, videos would be published as free and ad-supported on YouTube immediately followingtheir development. These videos could be used as standalone just-in-time training, as refreshersthroughout the pandemic, or as multimedia supplements to longer, more comprehensive e-learningcourses to reinforce key principals using a dynamic and engaging medium.Even before the pandemic, educators and researchers called for enhanced pathogen literacy in thegeneral public as an essential component of pandemic preparedness. This study proposes to collectvaluable data on learners' understanding of pathogen safety fundamentals and the potential efficacyof remote educational approaches to enhance microbiological literacy. Usability testing andknowledge retention (both immediately after training and three months later) research will beintegrated into the base Phase I study by testing these videos at the same time as those on opioidexposures. The initial products developed in this study may directly improve microbiological literacyamong at-risk populations, and these early studies may help to inform future training interventions.",2020,2021,"Gryphon Scientific, Llc",67326,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Emergency Responders,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control | Research on Capacity Strengthening,IPC in health care settings | Individual level capacity strengthening,2020 +C06707,3R44ES025448-03S1,Interactive Training in Emergency Operations for the Response Community,"In this competitive revision Phase II SBIR, Gryphon Scientific proposes to expand the scope of theongoing project to support the urgent need to develop and deploy training for two populations ofcitizen responders at risk of coronavirus exposure. The ongoing Phase II SBIR project focuses ontraining responders, including Community Emergency Response Teams (CERT) and the MedicalReserve Corps (MRC). We will expand the training for this group and add training for essentialworkers, a category of citizen responder that includes a large variety of occupations from transitemployees to grocery workers. The training content in our existing grant includes such topics asdisaster operations, deployment safety, mass casualty triage, and light search and rescue. Here,Gryphon proposes to incorporate a self-paced biopreparedness foundations minicourse and anadaptive role-playing minigame focused on pathogen safety for citizen responders. Building on therole-playing system, Gryphon also proposes to build interactive scenarios to train essential workerson core pathogen safety concepts. The full package will be deployed freely through app marketplacesfor self-service remote training. This training technology would reinforce the ongoing efforts bytraining organizations across the US to improve safety for at-risk workers performing essential jobfunctions. Recognizing that financial constraints pose a barrier to the sale of novel commercialtraining products, the app will be deployed at no out-of-pocket cost to organizations or trainees usingan advertising-supported business model commonly encountered in the mobile video-game market. Even before the pandemic, educators and researchers called for enhanced pathogen literacy inthe general public as an essential component of pandemic preparedness. This study proposes tocollect valuable data on learners' understanding of pathogen safety fundamentals and the potentialefficacy of remote educational approaches to enhance microbiological literacy. Usability andknowledge retention in citizen responders will be integrated into the base Phase II study. Anadditional study with essential workers will test their usability and knowledge gains from using remoteself-service learning products. Testers will be randomly assigned into three groups of 20 people who(1) use the app regularly for 3 months, (2) use the app once, at the start of the three-month period,and (3) a control group who do not receive the app. All testers will complete three short assessments:pre-training baseline, immediately post-training (or one week after the pre-assessment for the controlgroup), and approximately three months following the date of first training. The initial productsdeveloped in this study may directly improve microbiological literacy among at-risk populations, andthese early studies may help to inform future training interventions.",2020,2021,"Gryphon Scientific, Llc",153169,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health workforce,2020 +C06708,3U45ES006175-30S1,Training At-Risk Workers on the Corona Virus and Bio Safety Hazards (1),"In response to the COVID-19 pandemic that has swept the country, the USW Tony MazzocchiCenter and its training partners will use their decades of experience in health and safety trainingincluding infectious disease to provide information and support to workers and communitymembers. The program is designed to provide information on disease transmission andcontrols necessary to reduce its impact.Additionally, because physical distancing has become part of the ""new normal"", this programwill include support for each of the training partners to equip themselves to conduct trainingusing both online and blended formats. These modalities differ from the face to face trainingtypically conducted under our programs. The change in approach will require bothtechnological upgrades and a new way of sharing material.The three parts of this program include:Training and Outreach:-Produce and conduct web-based training on COVID-19 and its effect on workplaces andcommunities-Produce and conduct Spanish language trainings on COVID-19Developing and Deploying Advanced Technology:-Support online training platforms for the TMC and its training partners-Purchase of software or licenses-Purchase of training tools that support distance learningStrengthening the Special Emergency Response Training (SERTs) Program:-Onboarding four additional worker trainers to the SERTs team-Initial training on relevant topics concerning HAZWOPER and COVID-19",2020,2020,Steelworker Charitable/Educational Org,90292,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Economic impacts,2020 +C06709,3UL1TR003015-02S2,Provision of Clinical Data to Support a Nationwide COVID-19 Cohort Collaborative,"The unknown and changing characteristics of the SARS-CoV-2 pandemic have severely challenged theUnited States (U.S.) health care systems. The key to addressing many of these challenges is data andinformation sharing. To do this requires bringing together individual level health data from disparate systems intoa common structure that can be analyzed for answers to the important questions about COVID-19. Within the health informatics community there are two approaches to integrating data for analysis: (1)Federated data sharing which keeps the data at individual locations and allows for aggregated queries and (2)Harmonized repository that joins the data from the different sites into one database with a common data modelthat allows for individual or row level queries. While the federated approach is easier to implement and muchmore widely used, the harmonization approach is what is needed to address the challenges of the COVID-19pandemic since it will enable more impactful data analysis on the scientific questions surrounding this disease. The University of Virginia (UVA), the lead site for the cross-state integrated Translational Health ResearchInstitute of Virginia (iTHRIV), is well positioned to serve as an initial, pilot provider of data for the harmonized,analytic database being assembled by the National Center for Advancing Translational Sciences (NCATS)known as the National COVID Cohort Collaborative (N3C). There four reasons iTHRIV can do this at UVA: 1)iTHRIV has implemented the Observational Medical Outcomes Partnership (OMOP) Common Data Model(CDM) and this is not only the accepted CDM for data transfer to N3C but it also the target data transfer modelfor N3C, which will make the iTHRIV CDM a good choice to validate data transforms; 2) The iTHRIV informaticsteam have been active participants in the development of the COVID-19 Phenotype implementation in OMOPand we can thus quickly implement the data queries; 3) The iTHRIV data Commons utilizes an architecture whichincludes multiple CDM and this gives us the capability to expand data acquisition to all partner institutions iniTHRIV and to rapidly respond to changes required in data acquisition and transfer; and 4) The University ofVirginia has an IRB Reliance Agreement in place with SMART IRB and can rely on any non-UVA IRB that alsohas an IRB Reliance Agreement with SMART IRB, which will streamline our start-up process for participation.iTHRIV at UVA therefore provides an ideal pilot site for the N3C project, and brings the iTHRIV Commons andthe iTHRIV partners institutions to rapidly support rapid expansion to other CDM as a model for the largerconsortium. The Commons also provides a leading team-science platform during the follow-on phases of N3Cwhere researchers within Virginia can collaborate with others from around the U.S. and the world to analyze thedata collected in centralized repository by the N3C project and address impactful health problems for thecommunity.",2020,2022,University Of Virginia,50000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C06711,3U01AI142001-02S1,Assessing the determinants of durable protective immunity in SARS-CoV-2 infected human subjects,"PROJECT SUMMARYCoronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has already resulted in nearly 3million laboratory diagnosed infections and over 200,000 deaths worldwide. There is no known pre-existingimmunity to SARS-CoV-2 in humans or licensed therapeutics to combat or limit infection. In the absence ofthese pharmacological interventions, governments around the world have implemented stringent measures tothat curb the spread of SARS-CoV-2 to populations at risk of serious complications from infection. Efforts toidentify efficacious therapies and develop vaccines to counter infection and disease require time and ultimatelyneed to be guided by deep knowledge about this novel pathogen. Immune-directed therapies in particularrequire a detailed understanding of the immune responses generated not only in severe COVID-19 disease butalso in the vast majority of individuals who develop non-severe disease. Innate immunity serves as the frontlineresponse to counter the early stages of infection and but is also critical for regulating the ensuing adaptiveimmune response. In humans, anti-SARS-CoV-2 humoral immunity has gained significant attention while rolesfor innate immunity and memory T cell responses have not been extensively studied. However, knowledgegained from SARS-CoV-1 studies indicate that T cell immunity is critical in virus control. In these SARS-CoV-1infected mice, the induction of the innate type I Interferon signaling cascade is delayed. Yet mice lacking thisinnate immune response exhibited greater numbers of virus specific T cells in their lungs. Thus, thisdysregulated innate immune response impairs anti-SARS-CoV-1 T cell memory. Whether SARS-CoV-2infection induces protective memory T cells and if the durability of anti-SARS-CoV-2 T cell memory isinfluenced by innate immunity are all currently unexplored. In humans, the innate immune response induced innon-severe COVID-19 disease is not well characterized. However, preliminary studies in cultured cells andanimal models indicate that upon SARS-CoV-2 infection, there is a restricted and delayed induction of innateimmunity resulting in limited induction of cytokines and chemokines critical for immune cell recruitment. Wepredict that the vast majority of COVID-19 infected individuals will exhibit a dysregulated innate immuneresponse typified by delayed and limited inflammatory signaling. If true, such a compromised innate immuneresponse could in turn induce limited short-lived adaptive immunity. Indeed, studies from SARS-CoV-1infections indicate that humoral responses are short-lived in recovered patients. To our knowledge, no studieshave examined memory durability in COVID-19 subjects. In this proposal, we will interrogate samples from aprospective longitudinal cohort of Seattle residents to examine if aberrant T cell memory is induced duringSARS-CoV-2 infection and importantly if this impaired memory stems from dysregulated innate immunity.Furthermore, mechanistic studies in the hACE2 transgenic mouse model, where SARS-CoV-2 infection resultsin mild disease, will identify how innate immunity shapes anti-SARS CoV-2 T cell responses.",2020,2022,Seattle Children'S Hospital,338565,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C06713,3R43GM133284-01A1S1,A Web Service for Fragment-based Selectivity Analysis of Drug Leads,"AbstractSignificance: To date, no specific therapeutic drug or vaccine has been approved for the treatment of human coronavirus.Better, direct‐acting anti‐viral drugs and accelerated methods for identifying them are desperately needed. Having a largebody of diverse fragment binding simulation data for each CoV2 drug target represents a unique opportunity to acceleratepreclinical drug discovery for CoV2 protein inhibitors. In contrast to testing‐based approaches, understanding fragmentinteraction patterns provides chemists specific mechanistic information to guide lead optimization. We propose to (1)create comprehensive fragment maps for the full suite of CoV2 proteins; (2) build automated tools for enumeration andevaluation of compounds that address protease selectivity and inhibition at Spike protein ppi and allosteric sites; and(3) make these available worldwide through the BMaps Web application. As such, all anti‐viral researchers can benefit.Innovation: Generating thousands of fragment binding patterns for each of the known CoV2 protein structures is a novelscientific approach to the rational design of CoV2 antivirals. This would be the largest data source of fragment data onCoV2 drug targets available and the resource would be accessible by all scientists working to address the COVID‐19pandemic. The innovation proposed is to enable a new scientific approach to rational design for CoV2 antivirals based onthe analysis of fragment binding patterns using novel compound enumeration and evaluation methods.Aim 1: Generate fragment and water maps for the full suite of proteins involved in the coronavirus life cycle. Using hotspots for location bias, run ~1,000 fragment simulations on each consensus of 6 structures from molecular dynamics.Aim 2: Develop automated tools to accelerate the enumeration and evaluation of candidate inhibitor molecules. Twoapproaches are proposed: (1) adapt our test software to enumerate all available modifications with all fragments for agiven starting point and (2) use a Conditional GAN (Generative Adversarial Network) deep learning network to enumerateinhibitors from fragments, using discriminator networks to bias towards synthesizable molecules with good properties.Aim 3. Build a repository of candidate inhibitors targeting coronavirus proteins through a variety of different mechanisms.Overall Impact: The CoV2 protein‐fragment maps lead chemists to often non‐obvious ideas to progress their compoundstoward clinical trials. The ability to automatically enumerate and evaluate compounds from a large fragment maprepository enables broad access to target‐relevant chemical diversity, without tedious manual searching. A repository ofcandidate inhibitors targeting coronavirus proteins enables drug researchers to get started quickly.",2020,2021,"Conifer Point Pharmaceuticals, Llc",225000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Pathogen morphology, shedding & natural history | Health information systems",2020 +C06714,3UL1TR002556-04S1,Convalescent Plasma to Limit Coronavirus Associated Complications: A Randomized Blinded Phase 2 Study Comparing the Efficacy and Safety of Anti-SARS-CoV-2 Plasma to Placebo in COVID-19 hospitalized pa,"Abstract: There are not any scientifically proven or approved therapies for COVID-19. Convalescent plasma (CP), whichis plasma that is obtained from people who have recovered from COVID-19, contains antibodies to SARS-CoV-2, the virus that causes this disease. CP has a long and storied history of improving symptoms and mortalityfrom other pandemic diseases, such as 1918 and 2009 influenza and SARS, as well as a myriad of other toxin-mediated and infectious diseases. Thus, CP is a rationally based and readily available therapeutic option forCOVID-19. There are thousands of people who have recovered from COVID-19 in the New York City area whohave donated their plasma to help others who are suffering from this disease. This project is a collaborativerandomized blinded placebo-controlled trial to evaluate the efficacy of treatment with CP in hospitalized patientswith COVID-19 that is being conducted at three New York University (NYU) Langone Health hospitals inManhattan, Brooklyn and Long Island, Bellevue Hospital Center, and three Montefiore Medical Center (MMC)hospitals in the Bronx. We designed and launched this trial as the pandemic surged in NYC by rapidly developinga multicenter, well-powered Phase 2 trial via regional collaborations established by Einstein-Montefiore andNYU-Langone CTSAs with support from the New York Blood Center (NYBC). The hypothesis underpinning thetrial is that compared to placebo, administration of CP will avert respiratory deterioration, the main cause of deathin patients with COVID-19. The specific aims of this project are: 1) To examine whether CP decreases thelikelihood of respiratory deterioration in patients hospitalized for COVID-19 compared to placebo (saline solution,SS) at 14 days from administration, and 2) To identify associations between quantitative and qualitative SARS-CoV-2 antibody levels and clinical outcomes in patients hospitalized for COVID-19 who receive CP and placebo.The public health benefit of proof of CP efficacy against COVID-19, which has already caused 338,000 infectionsand 21,845 deaths in the United States and 187,250 infections and 1,127 deaths in New York City would be atremendous and public health advance that could save thousands of lives.",2020,2021,Albert Einstein College Of Medicine,4325153,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Prognostic factors for disease severity | Supportive care, processes of care and management | Phase 2 clinical trial",2020 +C06715,3R43ES031818-01S1,Immersive Modular Preparedness Intelligent Tutor (IMPRINT),"Project Summary/Abstract The novel coronavirus (SARS-CoV-2) highlights urgent training needs for the emergency first respondercommunity. In response to the ongoing COVID-19 pandemic, the Boston Fire Department (BFD) has reportedan increased frequency of firehouse cleaning and decontamination activities; however, there may be substantialvariability in decontamination protocol adherence across firehouses and personnel following responses toservice calls during the pandemic. This is due to deeply ingrained decontamination trained behaviors and a lackof available and effective training resources, ultimately increasing the risk of COVID transmission. Improperdecontamination between service calls increases firefighter and emergency medical services (EMS) risk ofexposure especially in circumstances of complex disasters. Therefore, the first responder community requires ameans of ensuring consistent and thorough decontamination procedures are followed by personnel. In response to the current pandemic, the National Institute of Environmental Health Sciences (NIEHS)Worker Training Program (WTP) is developing a series of PowerPoint slides to address emerging training needs[1]. Charles River Analytics and our partner, Lt. Michael Kates of the Boston Fire Department, propose to extendthe approach funded under the parent grant (Immersive Modular Preparedness Intelligent Tutor (IMPRINT);R43ES031818-01) to adapt and improve this training. Specifically, we will adapt materials developed by the WTPand other organizations (e.g., CDC, OSHA, BFD) into a training course focused on decontamination foremergency first responders. This supplemental work will include the development of complementary, interactiveVR-based training modules that provide individuals and small groups the opportunity to demonstrateunderstanding and proficiency. Furthermore, the VR presentation of individual and small group activitiesencourages active trainee participation and engagement while enabling emergency response trainingorganizations to provide distributed training. Distribution of training is critical to enable social distancing. UsingIMPRINT's virtual environment, trainees will not have to be collocated to participate in small group activities. Thiswill provide the emergency first responder community a means of conducting crucial training while avoiding largegroup gatherings. Finally, we propose to develop an evaluation process to measure training acceptability andeffectiveness.",2020,2021,CharRiver Analytics Inc,99892,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C06716,3R01AI134384-04S1,Unifying big data analyses for Sars-CoV-2 Research,"Summary: The COVID-19/SARS-CoV-2 pandemic is a once in a generation, ""all-hands-on-deck"" event for thescientific community. This pandemic is also the first in which real time genomic data are available,e.g. via GISAID [1], where genomic sequences are deposited daily. Vital insights about the virus andthe epidemic depend on rapid and reliable genomic analysis of diverse viral sample sequences bymultiple laboratories. Yet we repeatedly encounter the same avoidable shortcomings early in viralinvestigations, including COVID-19: lack of reproducibility, rigor, and data/analytic sharing. Onlyabout 10% of the published genomes have quality metrics, primary data (read files), or any level ofdetails on analytics, making these data irreproducible and unverifiable; over 40% of GISAIDsubmissions to date provide no information about how the sequences were generated. Essentialquestions about the extent of intra-host genomic variability (indicative of adaptation or multipleinfection), viral evolution (selection, recombination), transmission (phylogenetic andphylogeographic) cannot be answered reliably if researchers cannot trust/replicate the source dataand analytical approaches. One of the key goals/deliverables of this supplement will be the openanalytic workflows that can be used to curate and standardize genomic data, and high qualityannotated variation data.",2020,2022,Pennsylvania State University-Univ Park,374737,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C06717,3P30CA060553-25S5,Production of protein array for serum antibody screening,"We propose to purify SARS-CoV-2 proteins to build a plate or filter-based array for rapid assessment of antibody responses. Proteins will be expressed in E. coli and purified as recombinant proteins. The arrays will initially be constructed manually using a vacuum blot system or ELISA plates. If arrays prove useful, a robotic system will be retooled. In addition to proteins already under study, we would expand our library to include all of the smaller open reading frames, especially proteins E and M, which are 100% conserved with SARS. The SARS-CoV-2 proteome can be covered in a 30 protein array. These arrays would then be used to ask novel questions about the development of the immune response in different patient cohorts, including cancer patients.",2020,2023,Northwestern University At Chicago,395000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,1997 +C06718,3P30CA033572-37S2,A Phase 2 Trial of Leflunomide for the Treatment of COVID‐19 in Patients with Solid Tumors and Hematologic Malignancies,"Novel interventions are urgently needed to address the COVID-19 pandemic, especially for highrisk populations. Leflunomide is a dihydroorotate dehydrogenase (DHODH) inhibitor, impacting pyrimidine synthesis for DNA and RNA production, and has been in use for over 20 years for treatment of autoimmune diseases such as rheumatoid arthritis and lupus with an excellent safety profile [1, 2]. It has known anti-viral activity and has been applied against cytomegalovirus (CMV) and polyoma BK virus infections in immunocompromised hosts [3, 4]. Leflunomide is orally available and exhibits hepatic clearance and a long elimination half-life. In vitro and in vivo experiments conducted in Wuhan, China demonstrated DHODH inhibitors have activity against COVID-19, including teriflunomide, the active metabolite of leflunomide [5]. Moreover, our preliminary data at City of Hope also suggest that leflunomide significantly arrests viral RNA replication in cancer cells infected with a naturally-occurring RNA virus (reovirus) and impairs ex vivo IL-6 expression in virally infected peripheral blood mononuclear cells (PBMCs).",2020,2022,Beckman Research Institute/City Of Hope,440000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,1997 +C06719,3UL1TR002556-04S2,CTSA Administrative Supplement for Informatics Core: A novel AI/ML system to predict respiratory failure and ARDS in Covid-19 patients,"PROJECT Summary: The Einstein-Montefiore Institute for Clinical and Translational Research (ICTR) proposes an AdministrativeSupplement pursuant to NOT-TR-20-011, CTSA Program Applications to Address 2019 Novel Coronavirus(Covid-19). Specifically, this application addresses the urgent need for research on the coronavirus pandemicwith a project focusing on informatics and data science to preemptively identify patients with the life-threatening complications of SARS-CoV-2, using CTSA-supported core resources. Characterized by severehypoxemia, tachypnea, and decreased lung compliance, the diagnosis of acute respiratory failure (ARF) is abad prognostic sign, and in a subset, leads to development of acute respiratory distress syndrome (ARDS).The rates of Covid-19 infection and death in the Bronx have been higher than any other borough of NYC. Asthe major regional health system, our experience with Covid-19 provides guideposts that may prevent futurevictims of this pandemic. The bleak picture for ARDS in the 4,452 patients admitted showed that 78% of ourintubated Covid-19 patients developed ARDS, with 42% mortality. The overall goal of this proposal is toleverage our novel informatics and analytics platforms enabled by the Einstein-Montefiore CTSA (NIH/NCATS1ULTR002556), and extensive Artificial Intelligence and Deep Learning resources to implement a novel,situational awareness and clinical decision support system for ARF and ARDS (SA-ARDS). We will re-train ourexisting deep learning models with data collected from Covid-19 patients and contextualize its implementationwith data from the Covid-19 response during the pandemic in NYC. The SA-ARDS data platform will providelongitudinally integrated clinical data for research and multi-institutional and national collaborations, with thefollowing specific aims: Aim 1: To integrate, re-train, and validate our novel, near real-time, Electronic RiskAssessment System (ERAS 1.0) optimized for early recognition of ARF, ARDS, and inpatient mortality; Aim 2:To develop an evidence based, real-time, and context appropriate Situational Awareness clinical decisionsupport system targeting ARF and ARDS response (SA-ARDS); and Aim 3: Through our partner CTSAorganizations, to standardize and disseminate ERAS 1.0 and the SA-ARDS to other health systems, includingthe NYC consortium of CTSA hubs and the PCORI INSIGHT network. We will use the clinical data underlyingthe SA-ARDS to support research in local, regional, and national collaborations. All the methods and toolsdeveloped will be shared with the CTSA community via NCATS' National Center for Data to Health (CD2H).",2020,2021,Albert Einstein College Of Medicine,1003424,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C06720,3UG1DA015831-19S3,The National Drug Abuse Clinical Trials Network: New England Consortium Node,"PROJECT Summary: The coronavirus disease 2019 (COVID-19) pandemic poses unique threats to individuals with opioid usedisorder (OUD).1,2 They are likely to be particularly vulnerable to COVID-19 and the public health measures(i.e., social distancing) to control the disease.3,4 Specifically, individuals with OUD in remission may be atsubstantial risk for return to opioid use given disruptions in addiction treatment, such as medications for OUD(MOUD). In addition, stress due to social distancing, finances, loss of employment or housing may be a triggerfor return to use. COVID-19 may result in changes in illicit opioid supply and diverted buprenorphine andmethadone as programs and clinicians follow federal recommendations and provide patients with more takehome doses of methadone (increasing risk for overdose and diversion) and longer prescriptions ofbuprenorphine. Separately, there is concern that OUD-related stigma, lack of usual source of care, andpotential consequences of a positive test (e.g., housing situation), individuals with OUD may be less likely toseek a COVID-19 test even when clinically recommended. Importantly, all of these factors may vary widelybased on geography. To provide urgent insights on the potential impact of COVID-19 on individuals with OUDin four US cities, and informed by prior research,5,6 we will leverage the >700 patients enrolled in Project ED-Health (CTN-0069) and research infrastructure7 to reach individuals with OUD. Specifically, we will attempt tocontact all 738 individuals who were enrolled in Project ED-Health, at one of our four participating emergencydepartments (ED) located in New York, NY; Baltimore, MD; Seattle, WA; and Cincinnati, OH, to participate in afollow-up one time telephone-based survey. We will collect self-reported data on the impact of the COVID-19epidemic on opioid use and treatment and COVID-19 symptoms and testing. We will triangulate these datawith an electronic survey of medical directors and site-Principal Investigators at each site to capture data onthe impact of COVID-19 on ED presentations and experiences of patients with OUD. This work will beconducted by a team of investigators that has robust experiences in developing and implementing surveys,8-12linking self-reported and electronic health record data,13-15 and conducting longitudinal research with individualswith OUD.16-20 Thus, among a geographically diverse (Northeast, Mid-Atlantic, Midwest, West Coast) sample ofindividuals with OUD, we seek to characterize the impact of the COVID-19 pandemic on (Aim 1) OUDtreatment (engagement and access to MOUD), drug use, drug supply, and overdose risk, (Aim 2) COVID-19related symptoms and testing, and (Aim 3) ED leadership reports of the presentation of patients with OUD tothe ED, ED-based buprenorphine prescribing practices, and community treatment options. These timesensitive data are urgently needed to begin to understand the impact of COVID-19 among individuals withOUD to directly inform clinical interventions and policies.",2020,2025,Yale University,99904,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2002 +C06721,3U24DA044554-04S1,Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO),"Abstract: In response to the Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements andUrgent Competitive Revisions for Research on the 2019 Novel Coronavirus (Notice Number NOT-DA-20-047and linked Program Announcement PA-18-591) funding opportunity, the Collaborating Consortium of CohortsProducing NIDA Opportunities (C3PNO; U24DA044554) proposes a project to assess the impact of COVID-19on the participating cohorts' population of substance-using people living with HIV (PLWH) and those at high-riskfor HIV infection. Our innovative study proposes to collect data from a subset of participants from each of sevenparticipating C3PNO cohorts at two time points - in the height of the COVID-19 pandemic and during itsmitigation and control - in order to assess the impact of the COVID-19 epidemic on substance use for PLWHand those at high risk for HIV. We will use our current infrastructure and C3PNO validated harmonizationstrategies to compile new and existing data across the cohorts in order to: assess changes in social andindividual determinants of health during the course of the COVID-19 pandemic, to estimate differences insubstance-using behaviors of those who were confirmed/probable cases of COVID-19 (based on self-report ormedical record) and those who were not a confirmed/probable case, and to assess how PLWH and people whoare at high risk for HIV in C3PNO have different experiences in and responses to the COVID-19 epidemic ascompared to other HIV studies and cohorts that have less substance use. The C3PNO Coordinating Center atUCLA and Frontier Science will facilitate the design and implementation of a survey to collect data from a subsetof participants from each of seven participating C3PNO cohorts (ALIVE, HYM, JHHCC, MASH, mSTUDY,RADAR, and V-DUS). Participating cohorts will issue the survey to participants and transfer the resulting datato the coordinating center. If funded, this administrative supplement would allow a rapid and coordinatedcollection of linked COVID-19, HIV, and substance use data related to an ongoing public health emergencyaffecting the highly vulnerable substance-using populations followed by the cohorts. COVID-19 dataharmonization with other HIV cohorts will further aide our collective effort to understand the impact of COVID-19on HIV impacted communities. Finally, C3PNO's effort to assess changes in social and individual determinantsof health during the course of the COVID-19 pandemic as well as estimate differences in substance-usingbehaviors and the impact on PLWH or at high risk for HIV is both novel and critical in this time of unprecedentedsocial upheaval and instability.",2020,2022,University of California-Los Angeles,326106,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C06722,3UM1AI068634-14S1,"Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)","Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigationalagents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2infection. It includes a Phase II evaluation, with a seamless transition into a larger PhaseIII evaluation for promising agents.The trial is a randomized, controlled platform that allows agents to be added and droppedduring the course of the study for efficient testing of new agents against placebo within thesame trial infrastructure. When more than one new agent is being tested concurrently, thesame placebo will be used, when feasible.The primary outcome measures in the Phase II evaluation will be duration of symptoms,similar to the outcome used for outpatient influenza studies, detection of SARS-CoV-2RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a Phase IIagent will continue to be evaluation in Phase III will be made after the last participantrandomized to that agent or placebo completes their day 28 Phase II visit. If continued,data collected from participants enrolled in Phase II will be included in the Phase IIIevaluation.The Phase III evaluation is a continuation of the Phase II trial, for those agents that meetcriteria for further evaluation and for which sufficient study product is available. Enrollmentof those agents advancing to Phase III will continue for a fully powered trial to determinethe efficacy of each investigational agent compared to placebo to prevent hospitalizationand death in non-hospitalized adults with COVID-19. 1. The ACTG Leadership and Operations Center (LOC). A newly restructured LOC is proposed to provide scientific leadership and fiscal and organizational management of the ACTG. The ACTG Executive Committee (AEC) will serve as the overarching governing body of the network. Transformative Science Groups will oversee the development and execution of the ACTG research agenda, which will be coordinated and prioritized by the Scientific Agenda Steering Committee (SASC). Protocol development, implementation, training and network evaluation will be facilitated by the Network Coordinating Center at Social & Scientific Systems, Inc. The LOC financial management group at Brigham and Women's Hospital (BWH) will oversee resource management and protocol fund distribution at the direction of the AEC. The LOC will assure the engagement of Community in all aspects of the ACTG, and will coordinate communication between all three components of the network. 2. The ACTG Laboratory Center (LC). The ACTG LC will comprise Specialty Laboratories in virology, immunology, pharmacology, mycobacteriology and genomics equipped to perform protocol-specified testing and to advance the state-of-the-art by developing novel assays to address innovative pathogenesis-based questions arising from ACTG clinical trials. The LC will also oversee the quality management of all laboratories performing testing for clinical monitoring and primary endpoint determination. The LC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of LC activities with the research agenda of the network as a whole. Particular emphasis will be placed on building network laboratory capacity at international sites in resource-limited settings. 3. The ACTG Statistics and Data Management Center (SDMC). The SDMC will comprise the Statistical and Data Analysis Center (SDAC) at the Center for Biostatistics and AIDS Research (CBAR) at Harvard School of Public Health (HSPH) and the Data Management Center (DMC) at Frontier Science & Technology Research Foundation (FSTRF) in Amherst, NY. The SDMC will provide innovative approaches to the design and biostatistical analysis of ACTG clinical trials and laboratory studies; leads accurate collection of protocol specific clinical and laboratory datathrough electronic data capture; ensure data integrity, security and quality; and provide training to sites and laboratories. The SDMC will prepare regular reports to support the work of data monitoring committees overseeing the safety of ACTG trials. The SDMC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of SDMC activities with the research agenda of the network as a whole. RELEVANCE: The expertise provided by the SDMC will help advance research concerning the treatment of HIV-infected people or of diseases such as tuberculosis and hepatitis affecting these people. It will achieve this by ensuring that ACTG clinical trials and other studies are efficiently designed and analyzed to the highest standards. This research will continue to make significant contributions in advancing optimal treatment of HIV-infected individuals both in the Unites States and internationally.",2020,2020,Harvard University,655464,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2020 +C06723,3UG1DA049468-02S1,"New Mexico Clinical Trials Node: Clinical research and practice to address substance use in diverse, rural and underserved populations","As early as February of 2020, American Indian and Alaska Native (AI/AN) communities began to reportincreased prevalence rates of COVID-19 relative to the rest of the US. Compared to non-NHWs (21%), 34%of AI/AN adults are at greatest risk of COVID-19 related serious illness. AI/AN adults are also more likely tosuffer from underlying health conditions that further increases vulnerability to COVID-19 infection, such asdiabetes, cardiovascular disease, and cancer. These elevated risks are exacerbated by historical and politicalfactors, including population collapses from smallpox and the Spanish flu, low socioeconomicstatus, obstacles to accessing needed care and chronic underfunding of the Indian Health Service. Tovividly illustrate COVID-19-related disparities, AI/AN people comprise ~11% of the New Mexico population, yetaccount for more than 55% of COVID-19 cases in the state,10 with the Navajo Nation reporting 3,912 confirmedcases and 140 deaths (as of 5/21/20). To address the treatment needs of people with substance use disorders,especially opioid use disorder (OUD), during the COVID-19 emergency, federal regulations guiding addictionservices delivery have been modified, including within AI/AN communities. Changes include expansionof telemedicine and virtual behavioral health delivery, adjusting medication dosing strategies for OUD, andaltering reimbursement and confidentiality policies and practices for addiction services. Although these policyshifts were to promote availability and access, little is known about the adoption, implementation, andeffectiveness of these changes among programs serving AI/AN communities. Data is critically needed to informpolicy decisions following the COVID-19 emergency - that is, should policies be further developed andexpanded or, alternatively, rolled back. In order to ensure future policies decisions about addiction serviceinclude experiences and needs of AI/AN communities, rapid research on the dissemination, adoption, andimplementation of federal addiction policies among AI/AN-serving addiction treatment programs is of vitalimportance. The goal of this study is to rapidly investigate the dissemination, adoption, implementation, andsustainment of substance use and COVID-19 related policy changes among Tribal communities.The specific aims are to assess the dissemination, adoption, and implementation of COVID-19 policy and regulations at Tribal, State, and Federal levels by including quantitative questions to theCTN0096-1a National Tribal Addiction Survey (n=300) and examine the implementation and outcomes ofCOVID-19 policy and regulation changes at the Tribal, State, and Federal levels through qualitative interviewsconducted among providers and consumers (n=50).",2020,2024,University Of New Mexico Health Scis Ctr,148594,Human Populations,Other,Unspecified,Unspecified,Disabled persons | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Community engagement | Indirect health impacts | Health service delivery",2019 +C06724,3R01EB023808-04S3,"Wearable lung sounds, fluid, and body temperature monitoring for patients with COVID-19","The COVID-19 pandemic has tremendously impacted society, communities, and the healthcare system across the world, and threatens to continue to challenge society for the coming months and years. More than 1 million Americans have been diagnosed with COVID-19, and more than 60,000 Americans have lost their lives as of the writing of this proposal. The ultimate goal of this research is to create a wearable physiological sensing solution for COVID-19 patient management, including diagnosis, triage, and monitoring of patients based on lung sounds, lung fluid, body temperature, and inertial measures captured with the same device. The central innovation lies in the hardware and algorithms that have been proposed for this purpose, building upon the team's prior work in other areas of wearable bio-acoustic sensing and bioimpedance spectroscopy. The following two specific aims are proposed for the research: (1) to design, implement, and validate a wearable sensing system for lung sounds, lung fluid, body temperature, and inertial measurements; and (2) to test and evaluate this system to assess efficacy and potential information derived in patients hospitalized with COVID-19 and persons under investigation for COVID-19 longitudinally. Successful completion of this project would result in a validated prototype for sensing multiple parameters of cardiopulmonary health in patients with COVID-19, with imminent feasibility to transition the technology to commercialization and through regulatory pathways. This would provide a much-needed patient management technology for this novel coronavirus to healthcare practitioners and ultimately a means to monitor patients remotely to ensure that any deterioration in health is detected as early as possible.",2020,2021,Georgia Institute Of Technology,396542,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2016 +C06725,3R24AG063718-02S1,COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS),"1 Project Abstract/Summary of COMPASS 2 3 The COVID-19 pandemic has had widespread health, social, and economic implications that the 4 world has not experienced in modern history. It has brought to the forefront the significant health 5 disparities, socio-economic inequalities, and discrimination/xenophobia that exist, both prior to 6 and due to COVID-19. As a result of policies (e.g., shelter-in-place; social distancing) that have 7 been implemented, persons and communities who identify as racial/ethnic minorities, are low- 8 income, have limited English proficiency, and are socially and technologically isolated are 9 among our most vulnerable in terms of the adverse effects of COVID-19. Asian Americans and10 Pacific Islanders (AAPI), specifically, encompass all of these aforementioned characteristics.11 AAPI also experience significant health disparities, which has likely been exacerbated due to12 COVID-19, and reports of discrimination and xenophobia in the AAPI population due to COVID-13 19 are alarming. Older AAPI, especially, are more likely to be disproportionately affected by14 COVID-19 policies. Also, persons with health conditions such as cognitive impairment (i.e.,15 Alzheimer's disease and related dementias [ADRD]) may forget to perform precautions to16 prevent COVID-19 (e.g., handwashing). Caregivers' health may also be affected (e.g., less17 respite options; more care management responsibilities; fear/anxiety of infection for self and18 care recipients, economic instability). The goal of this time-sensitive proposed research, COVID-19 19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS), is to20 assess the effects of COVID-19 on AAPI. COMPASS will leverage potentially the largest21 registry of AAPI (n=10,000), Collaborative Approach for AAPI Research and Education (CARE)22 in ADRD, aging and caregiver-related research, to achieve this goal. CARE involves academic23 and community partners with decades of experience and successful track records in recruiting24 diverse AAPI in research in California. CARE will include AAPI who speak English, Mandarin,25 Cantonese, Vietnamese, and/or Korean representing more than 30 AAPI populations.26 COMPASS aims to recruit 2,500 participants from CARE and will also be available nationwide27 as an online survey. COMPASS participants will complete a comprehensive multilingual survey28 about their health, healthcare access, caregiving, discrimination experience,29 employment/income, and social support and coping strategies (e.g., via digital technology use).30 COMPASS is both a necessary and natural extension of CARE, and will help to inform future31 policies, programs and additional research that can alleviate the adverse effects of COVID-1932 for AAPI.",2020,2022,University Of California-San Francisco,619989,Human Populations,Asian | Other,Unspecified,Unspecified,Minority communities unspecified,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Health service delivery",2019 +C06726,3R44GM126848-03S1,Pdot-Enabled Point-of-Care Digital PCR for Sensitive Detection of SARS-CoV-2,"Project SummaryCurrent SARS-CoV-2 molecular diagnosis tests mostly are based on real-time quantitative PCR(qPCR). Digital PCR is a next-generation PCR technology based on limiting dilution, end-pointPCR, and Poisson statistics. Digital PCR transforms the exponential, analog nature of qPCRquantification into a linear, digital signal quantification. Compared to qPCR, digital PCR offersseveral important advantages, including its ability to provide absolute quantification, tolerance toinhibitors/contaminants, and its high sensitivity.Two recent studies showed digital PCR has improved sensitivity for picking up COVID-19 thatqPCR had missed. In addition, for some patients, results on SARS-CoV-2 infections from qPCRvaried from day to day. But unlike qPCR, digital PCR showed consistent reproducible results.Overall, digital PCR was shown to reduce significantly false-negative results, which isparticularly useful for diagnosing early or asymptomatic infections or for testing convalescentpatients before discharge.Current fluorescent probes used in qPCR, such as FAM (a fluorescein dye), do not have thebrightness to be visualized with a cell-phone type camera. To address this issue and to enablesimple cell-phone readout of digital PCR results in a point-of-care setting, this project aims todevelop Pdots into ultrabright probes for digital PCR assays that can provide sensitive detectionof SARS-CoV-2.",2020,2021,Lamprogen Inc,410204,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2017 +C06727,3R44GM125429-03S1,SBIR Phase II: Protein A Membrane Columns for Rapid Protein Purification,"Project Summary: This SBIR Urgent Competitive Revision will develop the first affinity membrane to purify therapeutic mRNA withhigh selectivity and throughput. mRNA-based pharmaceuticals have potential to address a wide variety ofpathologies. mRNA-based vaccines can increase safety and dramatically shorten development timelines inpandemic scenarios. A number of mRNA-based COVID-19 vaccines are under development, and one suchvaccine has completed its Phase-I clinical trial and showed great promise as a response to the COVID-19pandemic. However, a company pioneering mRNA medicines has revealed that the lack of high throughputdownstream purification processes is a major hurdle that must be addressed in the upscaling of industrialmRNA production to yield the necessary quantity and quality. Considering the profound impact that COVID-19will have on the global population of nearly seven billion people, the time to develop a high productivity mRNApurification technology, like the one proposed, is now. By addressing this challenge, the proposed technologywill have a significant impact on mRNA production and, by association, improve patient accessibility to thevaccine. Therapeutic mRNA usually possesses a polyadenylic acid (poly-A) tail. Oligo-deoxythymidine (oligo-dT) has been recognized as effective affinity ligand to isolate polyadenylated mRNA from feed streams viahybridization between adenine in the poly-A tail and deoxythymidine in oligo-dT. The goal of this CompetitiveRevision project is to demonstrate the feasibility of developing dT-based affinity membrane products with highbinding capacity for the rapid and selective purification of polyadenylated mRNA. Preliminary data are highlyencouraging. The products derived from this innovation will be first-in-market, disposable membranechromatography columns that can improve the mRNA purification productivity up to one hundred times withhigh purity and yield compared to conventional resin columns. The Specific Aims of the study are to (1)synthesize and characterize mRNA affinity membranes and (2) test prototype affinity membrane columns forcapture step purification of polyadenylated mRNA. In Specific Aim 1, Purilogics will evaluate the roles playedby ligand structure and density, synthesis conditions, and bind-and-elute conditions on capacity and recoveryusing a commercially available purified mRNA. In Specific Aim 2, Purilogics will collaborate with a partnercontract manufacturing organization to quantify membrane column performance for capture step purification ofpolyadenylated mRNA prepared with in vitro transcription (IVT) processes. The prototypes also will bebenchmarked against existing products. Multiple iterations of synthesis and performance characterization willimprove membrane performance. Immediate market entry for the new column products will be sales topurification scientists and engineers in biopharmaceutical companies.",2020,2021,"Purilogics, Llc",289381,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2017 +C06728,3R24AG063729-02S1,Social Distancing and Mental Health in Diverse Aging Populations,"New Jersey has the 2nd highest number of COVID-19 cases and mortality in the US, especially elderly withvulnerabilities such as Alzheimer's disease and related dementia (ADRD). Thus, the local governmentalresponse has drastically altered the daily activities of New Jersey residents, especially through the endorsementand enforcement of social distancing for the general public. While the theoretical benefits of social distancingare clear and it is a likely effective tool in reducing the spread of communicable disease like COVID-19, thereare known consequences of isolation and loneliness for older adults, which has been linked to numerousnegative health outcomes. The practice and impact of social distancing contains multiple facets, including thespaces which it is practiced, the activities it may impact, and the degrees to which it is practiced. NJ residentshave additionally experienced acute racial disparities in relationship to COVID-19 outcomes. The objective of this application is to leverage the infrastructure from the New Jersey Minority AgingCollaborative (R24AG063729) to prospectively quantify the impact of social distancing on mental health inAfrican American, Hispanic, and Asian aging populations, especially those with cognitive impairment, subjectivememory loss, or Alzheimer's Disease and Related Dementias (ADRD). In its first year, the parent grant has madesignificant progress in implementing its aims through the establishment and expansion of institutional capacityto foster academic-community partnerships. Through this parent project, we have additionally begun responsesto continue and expand community engagement throughout the COVID-19 crisis. Through a study of 600minority older adults (200 African American, 200 Hispanic, and 200 Asian), this administrative supplement aimsto link the infrastructure of the parent grant to understand the practice, experience, and impacts of socialdistancing (currently at its height) on mental health among minority older adults through biweekly/monthlytelephone interviews and weekly self-reported (social distancing practice and psychosocial wellbeing) through amulti-lingual, intuitive, and user friendly survey application. This study aims to: 1) Quantify the factors that leads to the adherence to social distancing amongcommunity-dwelling African American, Hispanic and Asian older adults; 2) Quantify the intended and unintendedconsequences (hygiene, psychological outcomes, social outcomes) of social distancing in above populations;and 3) Quantify the independent and potential joint influence of resilience factors (individual and family level)that might moderate the negative mental health consequences associated with social distancing in abovepopulation of older adults. We will additionally seek to understand the experience of social distancing amongminority older adults with cognitive impairment or Alzheimer's disease and related dementia (ADRD) throughadditional analyses. In totality, this administrative supplement will provide critical data and knowledge about thehealth and wellbeing of African American, Hispanic, and Asian older adults during the COVID-19 era.",2020,2022,Rutgers The State University of New Jersey,390000,Human Populations,Asian | Black | Other,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Indirect health impacts | Social impacts,2019 +C06729,3R44AI131756-03A1S1,Rapid generation and testing of live-attenuated vaccines against SARS-CoV-2,"There is a clear unmet need for a vaccine against the ongoing epidemic of coronavirus disease 2019 (COVID19) caused by SARS-CoV-2. SARS-CoV-2 was initially detected in the Hubei Province of China late in 2019.SARS-CoV-2 is highly contagious (R0 of 1.4-3.9, greater than seasonal influenza), and presents with fever,cough, fatigue, and shortness of breath. Older patients and those with underlying health conditions may be ata higher risk of severe illness, with most reported cases having occurred in adults (median 59 years of age).There are no vaccines or other medical countermeasures available against SARS-CoV-2. This submission is anAdministrative Supplement to 1R44AI131756-01 in response to NOT-AI-20-030, where we describe ourapproach to pre-clinical testing of our SARS-CoV-2 vaccine candidates. In the parent grant application,Codagenix is developing a safe and effective RSV vaccine based on Codagenix's algorithm-based platform forrapid generation of vaccines. Together, the respiratory illnesses caused by RSV and SARS-CoV-2 present majorpublic health threats. In this administrative supplement, we seek to apply our ""synthetic attenuated virusengineering' (SAVE) platform to design and develop a live-attenuated vaccine (LAV) against SARS-CoV-2.SAVE relies on large-scale DNA synthesis and rational re-design of a target virus to construct a vaccine that is""deoptimized"" for protein expression in human cells. The SAVE platform has been used to generate vaccinesagainst multiple viruses including influenza, Zika, dengue, RSV, and others. One SAVE-based vaccine iscurrently in the clinic in Phase I trials under a US IND, and another entering clinical trials in Q1-20,demonstrating the proof of principle behind SAVE. We already initiated the SARS-CoV-2 vaccine developmentin a real-time response to the ongoing epidemic of SARS-CoV-2. Using our SAVE platform, we designed sixvaccine candidates that are deoptimized to varying extents across the RdRp and Spike genes, along with asynthetic wt SARS-CoV-2. These genomes were synthesized de novo, assembled, sequenced, and are nowready for recovery following transfection in cell culture. Candidate vaccine viruses will be recovered underBSL-3 containment, passaged, deep sequenced, and screened for attenuation, immunogenicity and efficacy in aprimate model. We expect at least one, but likely 4 viruses will be recovered from transfection. Three of thebest-growing viruses (growing to >104 TCID50/ml) will be tested for safety, immunogenicity and efficacy inAfrican green monkeys, previously used for SARS studies. Following the completion of the work describedhere, using non-grant funding, two of the viruses that perform best in primate studies will be put through GLPtoxicity screening, GMP manufacturing and a Phase I clinical trials.",2020,2021,Codagenix Inc,1716496,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +C06730,3U24TR001608-05S2,COVID-19 Supplement - Center for Innovative TRIals in ChilDrEN and AdulTs (TRIDENT),"PROJECT SUMMARY/Abstract: The impact of the current COVID-19 global pandemic is likely underestimated. The specific impact on pregnantwomen, their infants and children is even less well characterized. We will use the infrastructure of the Duke /Vanderbilt Trial Innovation Center to address these knowledge gaps with three projects. We will use anexisting electronic data warehouse of clinical data from approximately 100,000 infants admitted to over 200neonatal intensive care units in the US to examine the epidemiology and outcomes through 12 months of agefor infants born to mothers during the current pandemic. Our collaborative research team, comprisingneonatologists and biostatisticians from the Duke Clinical Research Institute (DCRI) and the Pediatrix MedicalGroup, is uniquely positioned to complete this project. In addition, we will perform a direct-to-familyobservational study to evaluate the natural history of SARS-CoV-2 infection in children exposed to the viruspresumably via health care worker household contact. Up to 1000 children will be enrolled across the UnitedStates. We will identify households using existing registries/trials and will evaluate the rate of infection, viralshedding, and immune response of children exposed to SARS-CoV-2. Finally, to realize the full value of thedata collected as part of the multiple ongoing COVID-19 studies, data needs to be curated and harmonized.Here, data curation is defined as a metadata management activity that results in data with well-definedoutcomes and exposures. The majority of curation will occur at individual study level. After the data have beenharmonized, we will perform detailed quality checks. The resulting harmonized data will made availabel atdifferent timepoints to various audiences with the final result beign a publically available de-identitified dataset.As a result of this research, we will fill major knowledge gaps related to COVID-19 and improve public health.",2020,2023,Duke University,869057,Human Populations,Unspecified,Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2016 +C06731,3UL1TR002384-04S1,Disparities in COVID Disease Severity and Outcomes in New York City,"PROJECT Summary: This application is being submitted in response to Notice Number: NOT-TR-20-011 to highlight the urgentneed for research on the 2019 novel Coronavirus (COVID-19), and is an administration supplement to our parentgrant. The outbreak of COVID-19 and the life-threatening acute respiratory syndrome caused by the virus(SARS-CoV-2/2019-nCoV) have led to a severe, global public health crisis, and economic disruption. Sadly, inthis epidemic, NYC is the epicenter of epicenters. Some neighborhoods in NYC have been more exposed thanothers to COVID, and there seems to be clear correlation with the prevalence of COVID and its severity betweencertain ethnic and racial populations. Importantly, it is recognized that biology factors alone do not exclusivelyaccount for disease outcomes in those stricken with Covid-19. Social determinants have a significant impact onvarious health-related outcomes such as hypertension, diabetes, obesity, kidney and lung disease (1,2).Evidence also indicates that a myriad of social risk factors- such as low income, poor education, minority raceor ethnic background- coupled with inadequate community housing and resources, together with limited healthcare access and decreased health utilization, results in poor health outcomes and increased susceptibility andseverity to Covid-19 (3-14). For this study, we assembled a multidisciplinary team from Weill Cornell Medicine'sClinical Translational Science Center (CTSC); Englander Institute for Precision Medicine (EIPM), the WeillCornell's Center for Health Equity. The initial study will be conducted with the New York Presbyterian (NYP)Hospital health care system database involving ""hotspot"" areas in NYC with COVID. The NYP network is thelargest healthcare system by bed counts in New York City and is on the frontlines of the struggle against theCOVID pandemic. By discerning the interaction/relationship of the biology with the Social Determinants of Health(SDoH), we will gain further insight into why certain racial and ethnic groups are more susceptible to Covid -19,and why they develop the more severe forms of the virus. Furthermore, if we are able to identify the especiallyvulnerable, and provide adequate isolation and early medical intervention in the disease process- then we cansave lives. Protecting and providing preventive and early care for the vulnerable would also allow the remainderof society to interact in daily activities and prevent the economy from a major collapse. The less vulnerable whoare out in society would on average develop mild coronavirus infections. Consequently, once the larger andmildly affected less vulnerable population recover and gain natural immunity, the risk to the most vulnerablewould fall dramatically and the country would stabilize.",2020,2022,Weill Cornell Medicine - Cornell University,749219,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2017 +C06732,3R01AI148049-21A1S1,COVIDgene: Host genetics of SARS_CoV_2 infections,"Modified Abstract: The current COVID-19 pandemic causes illness, hospitalizations and deaths worldwide, and profoundly impacts global health including economic health. The severity of disease varies widely, but there is no evidence that a specific virus sequence is responsible. An estimated 15-20% of all infections require hospitalization with many of these patients progressing to acute respiratory distress (ARDS) and mechanical ventilation, cardiac and renal failure. Known co-morbidities such as older age (>65 years), diabetes, hypertension, pre-existing pulmonary disease, obesity, and smoking pre-dispose to such severe outcomes. However, among hospitalized cases there is tremendous heterogeneity in age, sex, and comorbidities with no clear understanding of disease pathogenesis. Viral differences and inoculum dose to not appear to be driving the differences in disease severity suggesting that host factors are important. Host genetics may influence pathogenesis in multiple ways including differences in immune response and viral shedding and partially explain this disease heterogeneity. A clear host genetic difference is especially likely to explain the instances of severe disease among young persons with no known comorbidities. Our hypothesis is that one or more host genetic polymorphisms predisposed otherwise healthy individual to severe COVID-19 infection. We plan to enroll 1500 individuals across the disease spectrum and to evaluate their serology for exposure and clinical characteristics and interrogate the human genome. We will also evaluate the hospitalized patients for cytokine expression and association with the host genome. This proposal has the potential provide an understanding of COVID-19 disease pathogenesis and identify those at greatest risk.",2020,2022,Johns Hopkins University,531120,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06733,3R42DA049655-02S1,Exhaled breath drug detection using differential mobility spectrometry,"Project Summary: This proposal seeks to expand upon breath analysis technology that is being actively studied as the focus of NIHgrant #6R42DA049655-02 and leverage this technology for rapid COVID-19 diagnostics. There is a dire needfor sensitive and specific diagnostic tests for COVID-19 that can be performed quickly. The differential mobilityspectrometry (DMS) breath analysis technology currently under investigation for drug detection may be adaptedto fill this void.During this supplement we will perform a biomarker discovery effort to determine the exhaled breath molecularspecies most suitable for use as a COVID-19 biomarker. Once a target species has been identified, methods ofcapture that can be implemented within the safety paradigm governing COVID-19 testing will be investigated.We will also initiate conversation with the FDA and develop an FDA approval strategy to expedite the deploymentof a future breath based COVID-19 diagnostic instrument based upon the technology being studied under thisadministrative supplement's parent grant.",2020,2021,Vox Biomedical Llc,59276,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06734,3U01AI069918-15S1,North American AIDS Cohorts Collaboration on Research and Design (NAACCORD) Renewal,"The North American - AIDS Cohort Collaboration on Research and Design (NA-ACCORD) is a collaboration of >20 academic and community-based prospective HIV research cohorts from the United States and Canada. It is the largest collaboration of HIV cohorts in North America and has been shown to be representative of the US HIV epidemic (according to CDC HIV Surveillance reports). Urgent COVID-19 questions can be answered by NA-ACCORD co-investigators using: 1) existing data in large-scale cohorts of people with (PWH) and without HIV (PWOH); and 2) newly established cohorts of people who have been tested for SARS-Cov-2 (regardless of the test result), which are enrolling participants every day. NA-ACCORD investigators will work collaboratively to share data collection instruments, algorithms for identifying COVID-19 disease, and analytic approaches to expedite answers to urgent questions in multiple data sources and understand the heterogeneity in findings. To answer urgent COVID-19 questions, this supplement will support: 1) assembling a team of experienced infectious disease epidemiologists and clinicians versed in longitudinal study design who are focused on answering urgent COVID-19 and understand heterogeneity in findings resulting from the same question being answered in different cohorts 2) the foundational steps to establishing 3 longitudinal COVID-19 clinical cohorts using EHR data 3) data management and analytic expertise specific to the profound health impacts of infectious disease using data from clinical (i.e. primarily EHR data) and interval cohort studies 4) establishing a library of COVID-19 surveys, person under investigation (PUI) forms, and other documentation forms from existing cohort studies, and providing a RedCap-based survey to NAACCORD cohorts in anticipation of future collaborative research 5) the development and sharing of EHR-based algorithms for COVID-19 and facilitating engagement with other groups working on common data models for COVID-19",2020,2021,Johns Hopkins University,906511,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Disease surveillance & mapping,2006 +C06735,3R24OD024624-03S1,A COMPREHENSIVE RESOURCE FOR HIGH-THROUGHPUT PROFILING OF WORM AND ZEBRAFISH METABOLOMES,"Project Summary Coronavirus disease 2019, also known as COVID-19, has created an unprecedented global health crisis.Thus far, the only strategy to minimize spread of the virus has been physical distancing. Unfortunately, theseefforts are negatively impacting the psychiatric health of the nation and devastating our economy. It is thereforeimperative that a treatment for COVID-19 be developed expeditiously. Worms (Caenorhabditis elegans) and zebrafish (Danio rerio) are premier model organisms that havehistorically provided profound insight into a number of human diseases. At this time, however, the applicationof worms and zebrafish to COVID-19 has been severely limited. Currently, the major issue is that there are noreported models in these animals to capture the complex pathophysiology of COVID-19. The overarchingobjective of the current proposal is to create a resource that will help bridge this gap. Specifically, we aim tofacilitate the application of metabolomics to COVID-19 related studies in worms and zebrafish. The basis of our work will be metabolomic analysis of human patients with COVID-19. In addition tocomparing patients with mild and severe disease, samples from an infected patient will be compared tosamples from the same patient after recovery. Together, we expect these experiments to provide acomprehensive picture of metabolic pathways that are altered during COVID-19 pathology. We will then map the metabolic dysfunction we uncover in patients to the worm and zebrafish metabolomesby using technologies that we have developed in the parent award. The result will be a resource delineating acomprehensive set of reference COVID-19 pathways in worms and in zebrafish. This will empower the use ofworms and zebrafish to answer important COVID-19 questions, two examples of which we propose to pursuehere. Our first question is: what is the mode of action of small-molecule drugs in clinical trials to treat COVID-19 patients (e.g., hydroxychloroquine)? We will perform dose-response metabolomics on zebrafish exposed to20 small-molecule drugs currently in clinical trials to treat COVID-19. A comparison of each drug's target toreference COVID-19 pathways will provide insight into mode of action, off-target toxicity, and potentially assistin the improved design of new drugs. Our second question is: which disease processes contribute to COVID-19 pathology? We will perform metabolomics on zebrafish models of cytokine storm, respiratory distress, andorgan failure. Comparing metabolic changes from each of these models to reference COVID-19 pathways willimprove our understanding of which disease processes contribute to COVID-19 pathology. We note that the drugs and disease processes that we propose to evaluate here are largely incomplete,with many additional drugs and C. elegans disease models available to test. These opportunities, and manyothers, represent exciting future applications of our resource to advance our understanding of COVID-19through the use of model animals.",2020,2022,Washington University,753340,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2018 +C06736,3P41EB017183-06S1,Center for Advanced Imaging Innovation and Research (CAI2R),"PROJECT SUMMARYCompetitive Revision to P41 EB017183 The Center for Advanced Imaging Innovation and Research (CAI2R) pursues a mission of bringing peopletogether to create new ways of seeing. The work of our Center has been focused on creating new paradigmsfor the acquisition, reconstruction, and interpretation of biomedical images, and on implementing newcollaboration models in order to translate these developments rapidly into clinical practice. In the proposed Competitive Revision, we will apply our experience in working with biomedical images andother signals to a new collaboration, aimed at the urgent need for COVID-19 testing.Parent Grant Summary The world of biomedical imaging is changing, and CAI2R has been at the forefront of that change. Tasksthat were once the sole domain of meticulously-engineered imaging hardware are now beginning to beaccomplished in software, increasingly informed by diverse arrays of inexpensive auxiliary sensors. Informationonce pursued through the laborious acquisition of carefully separated image datasets is now being derivedfrom newly integrated, and richly quantitative, data streams. In keeping with these themes, our Center will beorganized around the following four Technology Research and Development (TR&D) projects going forward:1. Reimagining the Future of Scanning: Intelligent image acquisition, reconstruction, and analysis.2. Unshackling the Scanners of the Future: Flexible, self-correcting, multisensor machines.3. Enriching the Data Stream: MRI and PET in concert.4. Revealing Microstructure: Biophysical modeling and validation for discovery and clinical care.Competitive Revision Summary With the appearance of COVID-19, the world changed suddenly. The need for definitive but also broadlyavailable COVID-19 testing is clear, and is identified as a top priority in the Notice of Special Interest (NOT-EB-20-008) to which this proposal responds. In this project, we will partner with colleagues in chemicalengineering and virology to develop, evaluate, and deploy a new electrochemical device for multifaceted point-of-care or home-based COVID-19 testing. The device will use molecular surface imprinting to create a goldsurface sensitive to SARS-CoV-2 spike proteins and other analytes of interest. Sensitive solid-stateelectronics will then detect the presence of these analytes in patient samples, ultimately allowing rapid andsimultaneous assessment of COVID-19 infection, immunity and severity. Specific Aims of the CompetitiveRevision are as follows:1. Prototype. We will test whether a COVID-19 signal may already be obtained using our best current imprinting methods and electronic detection circuitry.2. Characterize. We will use biobanked patient samples to establish sensitivity, specificity, and limits of detection (LOD) of our initial prototype for COVID-19, as opposed to other common viruses.3. Optimize and iterate. Informed by Aims 1 and 2, we will develop optimized electronics, surface imprinting protocols, and measurement strategies to improve sensitivity and specificity.4. Evaluate and distribute. We will test designs with promising performance prospectively in a cohort of subjects presenting for testing at NYU, and will compare results with standard RT-PCR COVID-19 testing, with an eye towards FDA approval, commercialization, and broader distribution.",2020,2021,New York University School Of Medicine,772877,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06738,3T15LM007092-29S1,BIC TRAIN - Biomedical Informatics COVID-19 Training,"Project SummaryFor Parent Grant: Harvard Biomedical Informatics and Data Science Research Training (BIRT) program, April 2016.This proposal for the Harvard Biomedical Informatics and Data Science Research Training (BIRT) programrecognizes that the field of biomedical informatics is an increasingly relevant, if not essential, field for medicineand research in the health sciences. The practice of clinical care and biomedical investigation each constitutecomplex enterprises that are dependent on the mastery of enormous data streams. There is a crucial need fortrained individuals who are able to integrate, interpret, and act upon the large-scale, high-throughput, andcomplex data that are generated in the course of biomedical research and the practice of medicine. The primaryaim of this proposal is to contribute to the cadre of highly trained independent and successful researchers inthe field of biomedical informatics.This proposal builds on the strengths of our many years of National Library of Medicine (NLM) fellowshiptraining. The current proposed program will be overseen and administered by the Department of BiomedicalInformatics at Harvard Medical School (HMS) and will involve collaboration with faculty at HMS and itsaffiliated hospitals, including Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham andWomen's Hospital, Dana Farber Cancer Institute, and Massachusetts General Hospital. In addition, theprogram will work closely with other Harvard University Schools in the university-wide data scienceinitiative, and, in particular, with its Data Science Education Working Group, of which the proposed PI is amember. We meet all requirements of the current NLM RFA, which focuses on those informatics areas thatdirectly pertain to health-related application domains. The breadth and depth of our research laboratories,real-world clinical systems, research activities, academic programs, and experienced faculty provide anoutstanding environment to mentor and instruct trainees in all four of the NLM-identified focus areas -healthcare informatics, translational bioinformatics, clinical research informatics, and public healthinformatics.We request support for a total of fifteen trainees per year: ten at the postdoctoral level and five at thepredoctoral level. In addition, we propose to train four short-term trainees each summer. BIRT trainees workwith internationally recognized faculty on high-profile grants and research projects. The program has a formal,required academic component, which includes the Master's degree for all postdoctoral trainees, and the PhDdegree for all predoctoral students. Trainees' overall progression throughout the training period is closelymonitored. Trainees are regularly evaluated through their course work and through progress on their researchprojects.",2020,2022,Harvard University,174995,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,Health information systems,1992 +C06739,3R41GM134782-01S1,Array Based Affinity Selection,"Project SummaryFunds are requested to apply technologies being developed in a current NIGMS award to generate recombinant antibody-like affinity reagents to the spike protein of the SARS-CoV-2 virus. As aproof-of-principle experiment, we have already isolated four fibronectin type III (FN3) monobodiesthat bind with low nanomolar affinity to the receptor binding domain (RBD) of the viral spike protein. An administrative supplement will permit continuation and expansion of this work to generateaffinity reagents that bind with picomolar affinity and can be used in sensitive, robust diagnosticassays (homogenous assays, lateral flow assays) for virus particles in saliva. Separately, thesemonobodies will be reformatted as bivalent Fc fusions and overexpressed in CHO cells. Suchreagents have the potential to serve as therapeutic agents that lower or block viral entry into patients ACE2-expressing cells.1",2020,2021,Tango Biosciences Inc,183318,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2019 +C06740,3U41HG007823-07S1,Establishing the GWAS Catalog as a resource for large-scale association studies,"Project Summary: Accelerating access and sharing of COVID-19 human host genetic and phenotype dataEarly evidence from twin studies suggests that approximately 50% of COVID-19 disease burden isdetermined by host genetics. The identification of host factors for COVID-19 will directly influence thedevelopment of public health intervention strategies and the identification of drug targets. There are a varietyof existing cohort longitudinal studies with existing genetic and clinical data, e.g. UK Biobank, AllofUs,23andMe, Ancestry.com who are engaging existing cohort participants for information on COVID-19 diseaseburden. The COVID-19 Host Genetics Initiative (COVID-19-HGI) is an international consortium that aims toidentify host genetic associations of COVID-19 by combining data from human cohorts. The EuropeanGenome-phenome Archive (EGA) and the NHGRI Analysis, Visualization, and Informatics Lab-spaceAnVIL/Terra platforms are founding partners that form the data sharing and analysis platform. The EGA is aGA4GH driver project and can rapidly acquire these data enabling ethical genomic data sharing. This extendsthe international data sharing infrastructure and processes enabling access to human controlled access datarelevant to addressing the COVID-19 pandemic.Aim 1: Host submissions to the COVID-19-HGI data sharing platformThe EGA has previously received submissions from over 144 US submitters and US based users represent33% of the total user community which streams 8.6 PB of data last year. The COVID-19 pandemic is expectedto significantly increase this number through planned new industrial collaboration (e.g. Ancestry.com,Regeneron Pharmaceuticals). There is an opportunity to develop new submission templates and processesto enable more rapid submission of genetic and phenotype data.Aim 2: COVID-19 host metadata harmonisationRecording and collection of clinical patient data of COVID-19 disease burden is a critical requirement.Phenotype information is collected using a variety of formats, coding schemes, surveys, and ontologies.Using the COVID-19-HGI data dictionary, we will construct a common minimal metadata model that will mapacross COVID-19 studies for genetic association studies.Aim 3: Rapid integrated data access and flow into COVID-19-HGI analysis platformRapid integration of new human genotypes and phenotyping will be essential to determine reliable and wellsupported genetic associations. The NHGRI AnVIL and Terra platform will be the analysis platform for theCOVID-19-HGI. We will use GA4GH standards to provide rapid data access and integration of US COVID-19 data. This will result in more rapid and seamless human data flow between EGA and AnVIL to provideadditional power to COVID-19 host association studies",2020,2022,European Molecular Biology Laboratory,168829,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2014 +C06741,3U45ES006155-30S1,AFC Hazardous Materials Worker Training,"With this application, the Alabama Fire College (AFC) requests supplemental funding to conduct COVID-19 specific health and safety training with public safety personnel, including healthcare workers and others that are considered essential workers during the COVID-19 response. Using current Bureau of Labor Statistics, there are over 556,000 public safety and healthcare personnel working in the region including those who will provide patient transport or are members of emergency response teams and have roles which will require them to respond to an infectious disease outbreak such as the COVID-19 pandemic. Most of these personnel work in rural areas or medically underserved areas which put them and the patients they serve at greater risk. All these target populations have in common the potential for exposure to persons infected with COVID-19 and other emerging infectious diseases, through direct contact with infected individuals as well as through surface contamination or other contaminated materials.Alabama and Mississippi contain many medically underserved areas, health professional shortage areas, health department with limited budgets and limited ability to conduct contact tracing, and limited access to professional occupational safety and health training programs.Unfortunately, federal funds for preparedness assistance have not reached public safety and healthcare professionals in the amounts sufficient to meet their needs for training. AFC and it's partner, UAB, will develop and implement evidence-based training tools that are locally-relevant and consistent with the NIEHS WTP Coronavirus Bio-safety Initiative and guidance from the Centers for Disease Control and Prevention (CDC), the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), as well as other recognized health professionals. The proposed project will bring critical training to over 400 participants in webinar, virtual simulation, YouTube video, and limited in-person training. Courses will also be available through AFC's learning management system to Native American tribes and other responders and essential workers, adding many potential trainees through distance education.",2020,2021,Alabama Fire College,150000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,1992 +C06742,3R44AI114079-03S1,A single antiviral to treat multiple opportunistic infections,"In response to the Notice of Special Interest regarding the Availability of Emergency Competitive Revisions forresearch on SARS-CoV-2 and COVID-19 (NOT-AI-20-034), the proposal herein is focused on the developmentof SARS-CoV-2 therapeutic candidates with broad-spectrum activity against multiple coronavirus strains. It issubmitted as an Emergency Competitive Revision (PA-20-135) to an existing NIAID SBIR Phase II award titled""A single antiviral to treat multiple opportunistic infections"" (R44AI114079). The existing Phase II award is basedon the discovery that human sirtuin-2 protein (SIRT2) modulates the replication and spread of many differentviruses. The applicant, Evrys Bio, LLC, has developed a lead series of >550 SIRT2 inhibitors that exhibit broad-spectrum antiviral activity. Excellent progress for the existing award has been made in the identification of aDevelopment Candidate ready for IND-enablement (DC). The candidates for DC selection show broad-spectrumactivity against human cytomegalovirus (HCMV) and other opportunistic agents causing disease inimmunosuppressed transplant patients. Indeed, Evrys SIRT2 inhibitors block the growth of many differentviruses in addition to HCMV, including DNA viruses (Epstein-Barr virus, BK virus, Hepatitis B virus) and RNAviruses (influenza A and B, respiratory syncytial virus, Zika virus, Junin virus, Marburg virus and coronaviruses).Of special relevance to this application, an Evrys SIRT2 inhibitor was shown to inhibit the production of progenyby the human alpha-coronavirus HCoV-229E (EC50 = 1.6 µM) and beta-coronavirus HCoV-OC43 (EC50 = 0.54µM). OC43 was studied in greater detail, and production of its N and M RNA as well as N protein weredramatically inhibited in human MRC-5 cells. This proposal leverages the funding and progress of the existingSBIR Phase II award to identify and advance a Development Candidate with broad-spectrum antiviral activity.Proposed competitive revision Specific Aims focus on development of SARS-CoV-2 aspects of the broad-spectrum therapeutic: SARS-CoV-2 activity will be tested to select the DC from among nine SIRT2 inhibitors(active against beta-coronavirus OC43) already satisfying Target Compound Profile criteria for developmentincluding broad-spectrum antiviral effectiveness and suitability for pharmaceutical development. To speed atherapeutic solution to patients in need, the selected broad-spectrum DC (including SARS-CoV-2 antiviralactivity) will be advanced through IND enabling studies. In parallel, a back-up DC will be obtained. Evrys hasextensively characterized the lead series with respect to quantitative structure activity relationships (QSAR)predicting HCMV antiviral activity and allowing for optimization of pharmaceutical properties. The algorithmswill be retrained for coronavirus to select a back-up optimized for coronavirus potency and pharmaceuticalproperties (e.g., good lung distribution) for treatment of COVID-19. Extension of the parent grant's original aimsis possible because Evrys' well-characterized SIRT2 inhibitor series exhibits broad-spectrum antiviral activity,including anti-coronavirus activity.",2020,2021,"Evrys Bio, Llc",901086,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06743,3UL1TR002535-03S2,CCTSI Participation in the National COVID Cohort Collaborative (N3C),"PROJECT SUMMARY/Abstract: This application is being submitted by the Colorado Clinical and Translational Sciences Institute (CCTSI; UL1TR002535) in response to NOT-TR-20-028, Clinical and Translational Science Award (CTSA) ProgramApplications to Address 2019 Novel Coronavirus (COVID-19) Public Heath Need, and PA-18-591, AdministrativeSupplements to Existing NIH Grants and Cooperative Agreements.The COVID-19 pandemic has had unprecedented global impact. In some patients, SARS-CoV-2 infection leadsto pneumonia, hyperinflammation, hypoxemic respiratory failure, acute respiratory distress syndrome, multipleorgan dysfunction syndrome, and death. Although rapid advances have been made in identifying risk factors forsevere COVID-19, there are currently no FDA-approved SARS-CoV-2 vaccines and only one emergency FDA-approved therapeutic (remdesivir). Most U.S. reports of COVID-19 clinical characteristics, treatments, andoutcomes have been from a single hospital or health system or have presented only summary statistics obtainedusing a federated query design. Progress in this field is significantly impaired by the lack of a large,centralized multi-center, row-level, high-granularity clinical data resource with which to develop and testhypotheses and develop novel predictive and diagnostic computational tools. Therefore, there is an urgent publichealth need to build such a centralized resource.The Specific Aims for this UL1 Administrative Supplement are: 1. Build a deep and adaptive COVID-19 ClinicalData Mart. We will leverage the CCTSI Informatics Core and our enterprise data warehouse to create a COVID-19 Data Mart that will include rich clinical data extracted from the electronic health records of large adult andpediatric health systems. We will harmonize the Data Mart to N3C's preferred common data model, theObservational Medical Outcomes Partnership (OMOP) model. 2. Share CCTSI COVID-19 case and controldata with N3C. We will secure appropriate regulatory approvals and data transfer agreements and securelytransfer harmonized COVID-19 data to N3C. 3. Co-Lead N3C Clinical Scenarios and Analytics. As one of theonly practicing ICU physicians in the CTSA Informatics Enterprise Committee, the CCTSI Informatics CoreDirector, Dr. Tellen Bennett, will play a key role in N3C by engaging other clinician-scientists and leadingprioritization and execution of clinical analyses. Taken together, these efforts will accelerate clinical and datascience research toward the development of better therapeutic regimens and predictive and diagnostic tools inCOVID-19.",2020,2023,University Of Colorado Denver,99812,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2018 +C06744,3UH3DE025483-05S1,Coordinated Oral Health Promotion (CO-OP) Chicago,"The Coordinated Oral Health Promotion (CO-OP) Chicago studies [UH2DE02583/UH3DE025483] werefunded by the National Institute of Dental and Craniofacial Research (NIDCR) as part of a consortium to developand test interventions to reduce oral health disparities in children. The resulting CO-OP Chicago Trial is a healthdisparities cohort of 420 very young children and their families. At entry into the trial, the mean child agewas 21.5 months old. Forty-two percent of participants describe themselves as Black race, and 54% as Hispanicethnicity. Most children (89%) had Medicaid health insurance. Many caregivers were struggling to brushchildren's teeth twice a day, provide a healthy diet, and take children for preventive oral healthcare. Multi-levelinterventions, such as community health workers (CHWs), are needed to target these factors that operate onindividual, family, community, and public health levels. COVID-19 has brought new changes to household dynamics and unforeseen stressors to thesefamilies. The medical clinics and social service agencies that service these families have also beenmajorly affected. As we begin the process of resuming health, dental, and social services, we need to considerwhat changes are needed. Challenges fall into several domains. (1) Dental care: Access to dental services waschallenging for low-income families before this crisis; this will worsen as providers and facilities attempt to resumeregular services while also catching up on those that had been cancelled and maintaining new safety protocols.Many questions regarding understanding of COVID-19, trust, safety, and logistics surround this process. (2) Oralhealth behaviors: With the disruption of schools, child care, and employment, how have oral health behaviorschanged? (3) Nutrition: How have dietary habits changed with food insecurity challenges and more time at home?(4) Mental health: How has the stress, household chaos, and alternation to social support systems associatedwith this pandemic affected families? We propose to answer these questions in the Community InterventionModifications for Low-Income Urban Families after COVID-19 study. The results will inform the interventionsdental, health, and social service agencies will need to provide in order to support high-risk families to establishhealthy oral health behaviors after a major societal stressor like COVID-19.SPECIFIC AIM: To determine specific intervention needs regarding dental care access, oral healthbehaviors, nutrition, and mental health for low-income urban families with young children followingCOVID-19. We will achieve this aim using quantitative and qualitative data collected from the CO-OP Chicagocohort and our 20 partner sites. Our hypothesis is that families will have poor mental health, food insecurity,disrupted home oral health routines, distrust of dental services, and challenges accessing dental care. We expecttargeted CHW outreach and care coordination will be the best interventions to address these issues. When it comes to long-term recovery from COVID-19, let us not `go back to normal.'",2020,2021,University Of Illinois At Chicago,239847,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery | Health leadership and governance,2020 +C06745,3U45ES006179-29S1,Hazardous Materials Worker Health and Safety Training,"The New Jersey / New York Hazardous Materials Worker Training Center will provide training for essential works to respond and work safely when faced with exposure to COVID-19. The Center will provide train-the-trainer course via distanceweb conferencing to expand the knowledge of trainers to provide the NIEHS developed COVID-19 training tools. Rutgers will provide the training for instructors at Make the Road New York and Wind of the Spirit. These instructors will then provide training for essential workers in the communities. Rutgers will partially fund MDB, Inc. to develop multi-step process to locate, organize, visualize, and present the critical information for workers. NYU School of Global Public Health (NYUGPH) will develop and launch online, interactive, mini-lessons geared around the recognition, evaluation, and control of infectious disease agents. NYUGPH proposes to develop 3 interactive lessons within each of the 3 modules (recognition, evaluation and control) for a total of 9 interactive lessons. World Cares Center (WCC) will deliver worker-based training to prevent and reduce the exposure of hospital employees, first responders, disaster volunteers and others who are at risk of exposure to SARS-CoV-2 through their work duties. NYCOSH will provide a 7-hour Infectious Disease and Industrial Hygiene Train the Trainer course for seven NYCOSH staff who regularly train other workers. The Center will train approximately 937 workers through this project.",2020,2021,Rutgers The State University of New Jersey,300000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,1992 +C06746,3R01AI148378-02S1,2) MVA based SARS-CoV-2 vaccines,"The overall goal of this proposal is to develop effective prophylactic vaccines against the novel SARSCoronavirus-2 (SARS-CoV-2) infection that has recently emerged as a pandemic across the world. The SARS-CoV-2 has already infected more than 120,000 people and over 4000 people died due to COVID-19, a diseasecaused by SARS-CoV-2. Thus, there is an urgent need for the development of a vaccine that can rapidly induceanti-viral immunity and prevent infection. Previous data from other related coronavirus infections such as SARS-CoV and MERS-CoV demonstrate that a strong neutralizing antibody response against the spike protein caneffectively prevent infection. Thus, a primary goal of this proposal is to develop a modified vaccinia Ankara (MVA)based vaccine that expresses SARS-CoV-2 spike protein to generate a rapid and strong neutralizing antibodyresponse both in systemic and mucosal compartments. There are several advantages to MVA based vaccinesthat include their excellent safety and a single dose of MVA vaccination can provide protection against multiplevirus infections including SARS-CoV, MERS, Zika and Ebola virus. A novel aspect of this proposal is that wewill compare the immunogenicity and protective ability of different forms of the spike protein with a goal ofinducing neutralizing antibodies against both SARS-CoV-2 and SARS-CoV. This proposal has two specific aims.The goal of Aim 1 is to generate MVA vaccines and characterizing the anti-spike antibody response in mice. Wewill also compare parenteral (i.m.) vs mucosal (intranasal) vaccinations to determine the best route for inducingmucosal antibody response. The goal of Aim 2 is to evaluate the protective efficacy of the MVA-based SARS-CoV-2 vaccines. There is an urgent and unmet need to develop and characterize small animal models forevaluating vaccine efficacy against SARS-CoV-2. Mice have served as an excellent model system to not onlyunderstand immunity to the related SARS virus but also for evaluating vaccines and antiviral therapeutics. In thisAim, we will develop and characterize a mouse model of SARS-CoV-2 infection and use this model to test theprotective efficacy of our MVA-based vaccine candidates. The completion of these studies will not only providea mouse model for SARS-CoV-2 infection but also develop vaccine candidates against SARS-CoV-2.",2020,2022,Emory University,292855,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Vaccine design and administration,2020 +C06747,3R43ES030580-01S1,Extending a digital risk mitigation intervention for workers deployed in diverse post-flood environments to address unique SAR-CoV-2 virus infection exposure risks in construction workplaces,"ABSTRACTFlooding events continue to increase in both frequency and intensity. Workers involved in post-floodreconstruction work are at increased risk of adverse health effects due to respiratory exposures and otherhazards. With the advent of the SARS-CoV-2 virus into the global community, these workers are even more atrisk for severe illness. Proposed e-learning platform ""Pocket Ark"" provides training before flooding occurs,real-time decision support during a clean-up, and communications capabilities during and after cleanup to theworkers involved. We propose to extend this project to include SARS-CoV-2 screening and education modules.Pocket Ark will be expanded to recognize early onset symptoms in workers and prevent its spread in theworkplace as well as provide training regarding risk reduction in the workplace, and resources to locate healthcare resources. This platform addresses an important public health problem and uses a novel app-based e-learning platform to improve and enhance the cognitive understanding of flood-related health hazards withinthis vulnerable working population.",2020,2021,"Radiant Creative Group, Llc",62559,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,,,2019 +C06748,3P41EB027062-02S1,Tissue Engineering Resource Center-Treatment of COVID-19 induced acute respiratory distress by inhalation of exosomes,"Summary: Tissue engineering is rapidly developing, but remains limited by (i) scaffold and bioreactor designs that arebased on predetermined parameters, and (ii) the lack of real-time, nondestructive measurements of celland tissue function. To overcome these two limitations, we will develop adaptive-responsive biomaterialsthat can sense environmental signals and actuate the cells, and imaging-enabled bioreactors with real-timespatiotemporal control of engineered tissues with feedback from the measured cell responses. Our goal isto offer these advances to the tissue engineering community, and translate them into clinic. The proposedTissue Engineering Resource Center brings together four highly productive and actively collaboratinginvestigators from Columbia University (lead institution), Tufts University and Columbia University MedicalCenter-Presbyterian Hospital. An Administrative Board will coordinate the Center's activities, in conjunctionwith an External Advisory Committee, formed from the world leaders in tissue engineering and clinicaltranslation that will evaluate the Center and provide guidance in strategic planning. The Center will partnerwith a number of existing resources (please see 13 letters of collaboration), and will have very generousfinancial support of the Columbia University School of Engineering ($2,425,000 over the five-year cycle).Strong and effective leadership is uniquely suited to support this transformative Center.The technical components of the Center are three Technology Research and Development Projects(TRD1: Adaptive-responsive biomaterials; TRD2: Imaging enabled bioreactor systems; TRD3:Regenerative engineering), eight Collaborative Projects and six Service Projects. We also propose arobust and diverse Training and Dissemination program to provide links between the projects in theCenter with training of biomedical investigators in the use of new technologies, and the outreach tostudents, general public and underserved communities. Our mission is is that the Center will serve as atransformative driving force for the field of tissue engineering, by developing and translating newtechnologies, providing training and service, and offering dissemination and outreach programs for generalpublic and high school students. With a highly innovative scientific premise, extensive foundationalresearch, strong leadership and institutional support, experience in translational research, and long historyof collaboration among the lead investigators, we are confident that the Center will accomplish its mission. ",2020,2021,Columbia University Health Sciences,467004,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",,2020 +C06749,3P30ES005022-33S1,A randomized crossover trial of portable air cleaners to reduce PM and SARS-CoV-2 exposures at home,"Abstract: Americans newly infected with SARS-CoV-2 (SC2) are directed to isolate at home with care provided byhousehold members. Isolation from others may be difficult to maintain for 2 weeks, especially in economicallychallenged households without enough space to create a private sick room and bathroom. The CDCrecommends that at-home patients and their caregivers use makeshift facemasks for care-giver protection.They do not address the possibility of virus spread via smaller particles that are not captured by improvisedfacemasks. Accumulating evidence supports the significance of patient-generated aerosols, with and withoutambient PM, in the transmission of SC2 infection, but haven't been subject to controlled study. U.S. PM2.5concentrations are linked to a 15% increase in COVID-19 deaths per ?g/m3 of PM2.5, suggesting an interactionbetween the two stressors. Thus, we plan to quantify SC2 in different PM fractions in home isolation rooms ofnewly diagnosed individuals Moreover, a common recommendation to reduce indoor aerosol exposures isfiltration, and based on our experience we plan a crossover trial of air cleaners in home isolation rooms. Wehypothesize that portable indoor particle filters will reduce both airborne PM and associated viral particleconcentrations in the air around patients. We aim to test this hypothesis by enrolling 20 individuals from ouremployee health clinics with newly diagnosed SC2 infections in a cross-over randomized trial of home aircleaners. These will be continuously operated alternately for two consecutive 24-hour cycles, one cycle with aHEPA filter, and the other with a sham filter. Size selective impactors in the isolation room will elucidateparticle sizes most associated with virus. Samplers will allow capture of PM2.5, PM coarse (10-2.5), and >PM10fractions. In both the isolation room and the main living area we will collect total inhalable particles (d<100 µm)at 10 L/min. These samples will be used in initial analyses to check if there is sufficient viral RNA in individualimpactor stages for reliable detection and quantification. Concentrations of PM and virus will be comparedbetween filtered and sham conditions .The greatest impact of our studies will be finding of a significant viralconcentration in the aerosol range (specifically, particles < 10 µm) documenting the potential for aerosolexposure to SC2. Finding substantial viral content in aerosol size fractions will have additional public healthimplications, as preventing person-to-person aerosol transmission is more challenging than preventingtransmission via larger droplets, the focus of almost all current prevention recommendations.",2020,2024,Rutgers The State University of New Jersey,254770,Human Populations | Environment,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",1997 +C06750,3R24OD022005-05S1,A Comprehensive Human cDNA Library For Functional Gene Replacement in Drosophila,PROJECT Summary: The recent pandemic of COVID-19 due to infection with the SARS-CoV-2 coronavirus has created an urgentneed to understand the biological mechanisms of pathogenesis of this new disease. The SARS-CoV-2 is acoronavirus with a slightly less than 30 kilobases (kb) long RNA genome that encodes 26 proteins that interactwith several hundred human proteins and initiate a number of pathogenic steps. Here we use the geneticmodel Drosophila melanogaster to understand gene and protein function involved in COVID-19. We willgenerate a library of UAS-cDNA constructs and transgenic flies to express and functionally assess the viralproteins. We will also generate transgenic flies for over 300 genes in the human genome involved in viralreplication and COVID-19 disease. We will generate Drosophila reagents for the Drosophila homologs of thesehuman genes using a unique drop-in technology and we will update the online hub for the dissemination ofthese resources to Drosophila labs throughout the world.,2020,2024,Baylor College Of Medicine,750329,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2016 +C06751,3U42OD011023-17S1,Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research Center,"The AIDS research portfolio at Yerkes National Primate Research Center (YNPRC) has continued to expandas demonstrated by a growth of approximately $12 million dollars (57% increase) in nonhuman primate (NHP)AIDS research grant funding over the past five years. This growth in grant funding is accompanied by a highdemand for Indian-origin specific pathogen free (SPF) rhesus macaques as the animal model for this research.YNPRC has maintained a colony of SPF rhesus macaques (previously with U24 support) in order to providethese animals for HIV/AIDS research. This application requests continued support (now a U42 mechanism) toexpand the SPF colony by maximizing production. The application includes the Overview; Husbandry andManagement Core; the Viral Testing Core; and the MHC Genetic Typing Core. This grant will support a subsetof the overall YNPRC SPF colony that derive program income from animal assignment fees and per diems.YNPRC will provide institutional support to cover remaining expenses for this colony as well as the remainderof the SPF colony.Management and Husbandry: To leverage the resources provided by the U42 to maximize production ofIndian-origin rhesus monkeys and facilitate allocation of these animals for NIH-funded HIV/AIDS research.Viral Testing: To provide serological and molecular viral diagnostic testing in support of the SPF colony and tomaintain a colony free of diseases that impact AIDS-related research at the Yerkes NPRC. In thissupplement we propose to develop and implement molecular and serologic methods for detectingSARS-CoV-2 infection and immunity in the SPF rhesus macaque colony at Yerkes National PrimateResearch Center.MHC Genetic Typing: To provide parentage testing, comprehensive analysis of MHC class I and class IIalleles, and to develop new techniques for detailed genetic characterization to support a genetically healthybreeding colony and provide genetic information on animals essential to the animal assignment process insupport of AIDS research. In this supplement we propose to define and determine the frequency ofdistinct ACE2 coding alleles within the YNPRC rhesus macaque breeding colony.Achieving these aims will ensure the Yerkes NPRC SPF breeding program is healthy, providing the necessaryanimals to support our HIV/AIDS research program using Indian-origin rhesus monkeys. The sustainability ofthis critical resource to scientists performing preclinical studies using the rhesus monkey model will have apositive, significant impact on the development of treatments to prevent or cure infection from HIV in people.",2020,2022,Emory University,799816,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2002 +C06752,3U42OD010918-21S1,The Mutant Mouse Resource and Research Center at the University of Missouri,"An overarching goal of the Mutant Mouse Resource and Research Center at the University of Missouri (MUMMRRC) is to provide refined mouse models to its users so that the broad range of disciplines in biomedicalresearch can advance efficiently and with optimal translatability. To do so requires constant assessment offactors that can modulate model phenotypes and development of means to control and even exploit suchmodulating factors. In the past decade, there has been an explosion of research on the role of one suchfactor, the gut microbiota (GM), in modulating murine models of disease. We and others have shown thatmultiple factors can influence the composition of GM and more importantly, that changes in the GM can altermodel phenotypes. With this in mind, the MU MMRRC seeks to develop means to provide models on differingcomplex GM that have optimal translatability. To this end, we have created colonies of mice that harbordiffering stable and well-characterized complex GM that represent the spectrum of GM seen in contemporaryrodent colonies. However, additional research is necessary to refine complex GM-associated experimentaldesign strategies. Most notably, there is need to incorporate other components of the GM such as viralinfections so that the GM of our laboratory mice better replicate the human condition. In this proposal, we willapply this concept to refinement and optimization of a major model for the study of SARS-CoV-2 infection, theB6.Cg-Tg(K18-ACE2)2Prlmn/J mouse. We will assess how increasing antigen exposure of mice throughsupplementation of standardized complex GMs with selected viral and bacterial agents will modulate thephenotype of this model. Results generated will be invaluable and immediately applicable and to ongoingstudies of the devastating COVID-19 pandemic and mice developed will be immediately available to thebiomedical research community. Moreover, this strategy can be readily applied to any additional models forSARS-CoV-2 infection that arise in the near future.",2020,2025,University Of Missouri-Columbia,385120,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2000 +C06753,3P40OD028116-01S1,Nonhuman Primate Antibody Resource for Immune Cell Depletion,"Project Summary: The Nonhuman Primate Reagent Resource (NHPRR) develops recombinant biological materials to supportresearch with animal models of human diseases. In our parent P40 award, we produce and distributeapproximately 400g of recombinant protein reagents per year. Therefore, we have the tools, expertise, andinfrastructure to manufacture recombinant reagents and distribute them widely. Very recently, coronavirussevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID) was declared a pandemic,which prompted the development of new animal models. Unfortunately, the potentially infectious nature ofCOVID samples has precluded the exchange of reference serum samples among centers developing monkeymodels of COVID. Thus, our plan is to create safe recombinant reference macaque immunoglobulin standardsto facilitate the development and validation of reliable assays for the detection of pathogenic coronaviruses andantiviral antibodies in NHP animal models of COVID. Specifically, this supplement will fund the generation of thefollowing reagents: recombinant coronavirus-reactive rhesus monoclonal IgGs (Aim 1) and NHP serum referencestandards (Aim 2). These macaque reference antibody reagents will improve the performance and comparabilityof antibody-based assays for NHP models by facilitating serum assay development, proficiency training, andinter-laboratory performance comparisons at the NPRCs (see letters of support).",2020,2024,University of Massachusetts Chan Medical School,323571,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C06754,3R01DA046620-02S1,"Reducing Drug-Related Mortality Using Predictive Analytics: A Randomized, Statewide, Community Intervention Trial","The COVID-19 pandemic is colliding with the ongoing drug overdose epidemic, a public health crisis that hastaken over 750,000 lives in the United States over the past two decades. The pandemic and associatedpolicy responses will have lasting impacts of the lives of people at risk for overdose. Moreover, the immediateeffects of the pandemic on access to overdose prevention and treatment resources, as well as fatal andnonfatal overdose rates, are in need of urgent study. This research will determine how policies enacted as aresult of the COVID-19 pandemic response have affected both access to overdose prevention and treatmentresources, as well as rates of fatal and non-fatal overdoses in the community. The effect of acute changes onCOVID-19 related diagnoses, hospitalizations, and deaths on subsequent spikes in fatal and nonfataloverdose, particularly in racial/ethnic and economically distressed communities, will also be examined.Documenting these impacts will provide important insights into the types of health service measures thatneed to be put in place during future disasters to avoid escalation of drug overdose risk. The study will takeplace in Rhode Island, a state with the 4th highest COVID-10 diagnosis rate and the 7th highest COVIDassociatedmortality rates in the nation (as of May 18th, 2020). In Aim 1, we will determine how policiesenacted as part of the state's COVID-19 pandemic response have influenced both access to and utilization ofharm reduction resources (e.g., naloxone) and engagement in substance use treatment, as well as rates offatal and non-fatal overdoses. In Aim 2, we hypothesize that various measures of COVID-19 disease burden(e.g., diagnosis rates, hospitalizations) will predict subsequent spikes in fatal and non-fatal overdose, and thatthese spikes will be particularly pronounced in economically distressed and racial/ethnic minoritycommunities. This work will help build an urgently needed evidence base to determine how best to effectivelymanage the adverse effects of COVID-19 on the overdose epidemic, and to support addiction-related healthand social service systems during unanticipated public health crises in the future.",2020,2024,Brown University,168548,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C06755,3P30CA013148-48S2,COVID-19 and Its Implications for Cancer Prevention and Control: A Collaborative Effort Across Cancer Centers,"The unexpected COVID-19 pandemic has the potential to trigger major behavior changes worldwide,which, consequently, may have significant implications for cancer prevention, management, and survivorshipefforts, particularly among sub-populations experiencing cancer disparities. Thus, it is imperative to beprepared and adapt our ongoing and future strategies across the cancer care continuum within this newcontext through participatory evidence-based approaches. Given the urgency, and how rapidly these changesare occurring, we must take advantage of ongoing collaborative efforts to maximize resources and accelerateimplementation of these new strategies based on the needs and wants of different sub-populations in the U.S.The overall goal of this collaborative with four other cancer centers (Iowa, Detroit, Colorado, and Ohio) is towork together to rapidly develop a standard set of core questions to incorporate into surveys that can beadministered to populations across the U.S. using protocols that can be delivered by cancer center/universitystaff working remotely (e.g., online and telephone). Although five cancer centers are moving forward with thesupplement, other cancer centers are willing to join our efforts so we have begun a coordinated effort toengage them in the process in the event additional resources become available. The specific aims are:1. To assess how differences in demographics (rural/urban, age, gender, race, educational attainment) willimpact engagement in cancer preventive behaviors (e.g., tobacco cessation) and cancermanagement/survivorship behaviors (e.g., adherence to treatment, adherence to surveillance) in thecontext of COVID-19 environmental constraints (e.g., social distancing, employment, mental health, etc.)among adult healthy volunteers, cancer patients, and cancer survivors in Alabama (field center);2. To provide coordination of efforts and technical assistance regarding data management and analysis to allparticipating cancer centers (coordinating center);3. To strengthen the collaboration with the participating cancer centers toward the development andimplementation of cancer prevention & control strategies in the context of COVID-19 (coordinating center)",2020,2021,University Of Alabama At Birmingham,371250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Indirect health impacts | Health service delivery,1997 +C06756,3R01DE007389-30S1,Novel Role for the P2Y2 Receptor in the Autoimmune Disease Sjogren's Syndrome,"Salivary gland dysfunction is symptomatic of Sjögren's syndrome (SS), an autoimmune disease associated with lymphocytic infiltration of the salivary gland. A commonality between many human autoimmune diseases, including SS, is chronic inflammation whereby sustained accumulation of immune cells promotes tissue degeneration and often leads to other damaging effects. A major focus of the parent grant for this supplement is to identify the functional relevance of extracellular nucleotide ""alarmones"" that are produced at the site of initial tissue damage. We have shown that G protein-coupled P2Y2 receptors (P2Y2R) for ATP and UTP are early responders to released nucleotide alarmones and that knockout of the P2Y2R in a mouse model of SS prevents infiltration of B and T lymphocytes into salivary glands, indicating a loss of the systemic immune response. We hypothesize that chronic inflammation in SS salivary glands is mediated by P2Y2Rs through activation of several signaling pathways through its distinct structural motifs. The Specific Aims of the parent grant are to investigate the cell mechanisms that initiate chronic inflammation at the level of P2Y2 receptors and to test the potential of targeting the P2Y2R in SS to prevent a systemic immune response. Directly relevant to this supplemental proposal, we have identified an Arg-Gly-Asp (RGD) sequence in the 1st extracellular loop of the P2Y2R and conclusively demonstrated its direct interaction with and activation of RGD-binding integrins. Corona Virus Disease 2019 (COVID-19) is a highly infectious disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) to attach to cells via a receptor-binding domain (RBD) located on its Spike (S) protein. Interestingly, the S protein RBD also contains an RGD motif, suggesting that RGD-binding integrins may be co-receptors with ACE2 for S protein. Thus, considering the presence of an RGD motif in the SARS-CoV-2 S protein RBD and the established interaction between ACE2 and integrins, we hypothesize that P2Y2Rs and RGD-binding integrins modulate SARS-CoV-2 entry. In addition to lung tissues, ACE2 is also expressed in oral epithelial cells, particularly in the tongue. This finding suggests that the oral cavity is susceptible to SARS-CoV-2 infection, which presents a significant concern for potential infections associated with dental procedures. Thus, this supplement offers a unique opportunity to test the novel hypotheses that SARS-CoV-2 entry in oral epithelial cells is dependent on RGD-containing S protein association with RGD-binding integrins that act as a co-receptor with ACE2 and that this interaction underlying COVID-19 can be modulated by RGD-containing P2Y2Rs that bind to these same integrins. These studies potentially offer an innovative translational approach whereby patients undergoing dental procedures could be administered a P2Y2R or integrin modulator via mouthwash or mouth spray that would reduce SARS-CoV-2 entry into oral epithelial cells, thereby preventing viral transmission.",2020,2021,University Of Missouri-Columbia,232102,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history",1992 +C06757,3P30CA093373-18S3,Cancer Center Support Grant P30,"The purpose of this 12-month study, ""Impact of COVID-19 on cancer-related behaviors among nonmetropolitan and minorities in inland northern California: Seeking mitigation strategies"" is to measure the impact of COVID-19 on cancer-related behaviors among 1,000 adult respondents and to explore whether telemedicine could be a mitigating factor. These respondents will intentionally over-represent non-metropolitan residents, African Americans, Native Americans, and populations who have Limited English Proficiency. Briefly, the aims are to [1] finalize IRB-approved instruments to measure the impact of COVID-19 on non-metropolitan and minority residents; [2] conduct data collection from these vulnerable populations in the UCDCCC catchment area; [3] disseminate findings to affected populations and to the NCI and professional audiences with the intent to apply insights to mitigation strategies. This Study will utilize qualitative data collection methods, e.g., mail, phone, FaceTime or its Android counterparts, and in-person to characterize responses from non-metropolitan residents, Native Americans, and populations who have limited English proficiency and qualitative research methods (key informant interviews and focus groups) to compile and develop responses from African Americans so that a patient-centered, telemedicine approach could be enhanced. These different methods reflect the premise that ""one size does not fit all"" and will facilitate the outreach strategies and opportunities in place. Successful achievements of these Aims will result in data that are not only aggregated for the full sample but also dis-aggregated by group (e.g., Native Americans) so that potential solutions might also be customized and shared with collaborators which include Feather River Tribal Health, Northern Valley Indian Health, bilingual/bicultural workers, and UC Davis Comprehensive Cancer Center.",2020,2021,University Of California-At Davis,167310,Human Populations,Black | Other,Unspecified,Rural Population/Setting | Suburban Population/Setting,Minority communities unspecified | Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Communication | Indirect health impacts | Health service delivery,2002 +C06758,3P01AG005842-32S1,Improving Health Outcomes for an Aging Population - Project 1,"OTHER PROJECT INFORMATION - Project Summary/AbstractSupplemental Project: The Impact of the COVID-19 Pandemic and Subsequent Economic Downturn onPopulation Health and MortalityThis project supplements an ongoing program project on ""Improving Health Outcomes for an Aging Population""by analyzing the impact of the COVID-19 pandemic and its associated economic downturn on population healthand mortality. As significant as the reported mortality statistics from COVID-19 have become, they do not accountfor undiagnosed cases of COVID-19, the health and mortality costs of deferred or foregone care for otherconditions, or the secondary health effects of economic distress, job loss, and social isolation. Also absent isany understanding of how these wider health effects are influenced by policy responses, notably social distancingrequirements at the local and state levels, and their associated effects on business activity. While COVID-19 isfundamentally a public health crisis, focusing exclusively on its direct health effects, without accounting for theimpact on the health care system and the economy -- and in turn the economy's impact on health, provides anincomplete understanding of the pandemic's overall impact on health and wellbeing. The goal of this supplementis to engage a small network of economic scholars to analyze near real-time data on health and mortality, andto begin to unravel these indirect and secondary health implications of the pandemic. The supplement's aimsencompass three categories of analysis on the secondary impact of the pandemic on health and mortality: (1)other health conditions affected indirectly by the pandemic, and how both the direct and indirect health impactsvary across race, ethnicity, and socioeconomic groups; (2) the dramatic economic downturn of the pandemicand the distinct impact of economic conditions on health and mortality; and (3) the social distancing policyresponse of different communities and states, and its relationship to economic conditions, health and mortalityat the local and state levels.",2020,2023,National Bureau Of Economic Research,447421,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts,1997 +C06759,3UL1TR002544-03S4,Tufts Clinical and Translational Science Institute (N3C Supplement),"PROJECT Summary: Tufts Clinical and Translational Science Institute (Tufts CTSI) is based on the conviction thatauthentic involvement of the entire spectrum of clinical and translational research (CTR) iscritical to fulfilling the promise of biomedical science for meeting the public's needs. Thisincludes not only from translation from bench to bedside (T1 translation), but also, crucially forhaving health impact, translation into effective clinical practice (T2), care delivery and publichealth (T3), and health policy (T4). Advances on all of these fronts is increasingly dependent onmaking effective use of scientific data from multiple domains.The COVID-19 global emergency presents both an immediate challenge and an opportunity toprogress on important data sharing aims emphasized by NIH. In response, NCATS and theCenters for Translational Science Award (CTSA) hubs, several HHS agencies, and otherpartnering organizations have committed to developing a next-generation repository for clinicaldata related to COVID-19, the National COVID Cohort Collaborative (N3C), as a means ofaccelerating global research into the disease and aiding the development of diagnostics,therapeutics, and effective vaccines. The N3C initiative's goal of improving the efficiency andaccessibility of analyses with clinical data is consistent with the primary informatics objectives ofTufts CTSI, which am to reduce barriers to the integration of healthcare and research byproviding innovative systems, data repositories, and analytical tools, and by enabling greaterexchange and collaboration through interoperability, standardization, and resource sharing. In-line with shared objectives, in this supplement we seek to contribute to the N3C initiative as adata provider and thought partner through the following specific aims: (1) continue to play animportant role providing tools and resources for N3C's analytics platform; and (2) ensure TuftsCTSI's Informatics Program has sufficient staff and technical resources to continue to provideCOVID-specific patient data from our hub to the N3C repository.",2020,2023,Tufts University Boston,100000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2018 +C06760,3UL1TR002378-04S2,Georgia Clinical & Translational Science Alliance (GaCTSA),"EFFECTIVE ALLOCATION OF TEST CENTERS FOR COVID-19 USING MACHINE LEARNING AND ADAPTIVE SAMPLINGAbstract: A critical task in managing and dealing with COVID-19 in communities is to perform diagnostic and/or antibody tests toidentify diseased individuals. This information is critical to public health officials to estimate prevalence and transmission,and to effectively plan for required resources such as ICU beds, ventilators, personal protective equipment, and medicalstaff. Additionally, information on the number of infected people can be used to develop probabilistic and statistical modelsto estimate the reproduction number of the disease, and to predict the likely spatial and temporal trajectories of the outbreak.This provides vital information for planning actions and preparing policies and guidelines for social-distancing, schoolclosures, remote work, community lockdown, etc. Despite the importance of diagnostic testing and identification of thepositive cases, broad-scale testing is a challenging task particularly due to the limited number of test kits and resources. Ourproposed research focuses on the development machine learning-based allocation strategies for determining the optimallocation of COVID-19 test centers, including mobile and satellite centers, to minimize the local and global predictionuncertainties, maximize geographic coverage, associated with projections of spatio-temporal outbreak trajectories, and toimprove efficient identification of diseased cases.",2020,2022,Emory University,225579,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2017 +C06761,3R24OD018559-06S1,Groundwork for a Synchrotron MicroCT Imaging Resource for Biology (SMIRB),"Project Summary: We request a high-flux x-ray source and to acquire new team expertise in segmentation from microCT images,in order to apply a new 3D form of histology developed through our parent R24 to begin to characterize thecellular and tissue geometries of COVID-19-associated Acute Respiratory Distress Syndrome (ARDS)pneumonia, our pandemic's most common cause of death. Our novel imaging tool, X-ray histotomography, isbased on microCT of fixed and metal-stained tissue. It is unique among 3D imaging methods as the onlynondestructive way to achieve pan-cellular imaging (allowing characterization of all cell types and tissues) andis potentially practical. Histotomography uniquely allows direct comparison with today's 2D standard of tissuediagnosis, histology, capable of producing both 3D renderings and undistorted 2D slices at any angle and anyslice thickness. Unlike histology, we will also allow us to precisely characterize cellular arrangements into tissuesafter fixing and staining of samples with metal. The ability to volumetrically characterize cell types and theirarrangements in acute respiratory distress syndrome (ARDS) is particularly important because it is what killsmost patients in coronavirus-based pandemics, including SARS (severe acute respiratory syndromecoronavirus) in 2003, MERS (Middle East respiratory syndrome coronavirus) in 2012, COVID-19 now. Theproposed work will increase our preparedness for future pandemics. ARDS lungs are an ideal human tissuemodel for mathematically defining human disease because all cell types are affected. The proposed work withCOVID-19 lungs will increase the precision with which we understand the different stages of coronavirus lunginfection and serve as a model for characterizing the Geometry of Disease across all organ systems.Histotomography in the parent R24 is currently limited to animal models, focusing on the zebrafish. Thesupplement will allow us to translate our work to human health, which was originally envisioned by the PI, aspart of defining the ""Geometry of Disease"". Our experience with this technology tells us that we will be able tocharacterize the numbers of each of the basic inflammatory cell types, including lymphocytes, neutrophils, andmacrophages (which are morphologically distinct) in terms of numbers, volumes, shapes, and density in theinflamed tissue, and to also characterize the changes in the lung epithelia (bronchial ciliated epithelial cells andpneumocytes, cell death, and the filling of airways with fluid and fibrinous exudate, and vascular inflammation.In addition to quantitation of tissue changes, we will also be able to visualize pathological change in the tissuesusing virtual reality. Histotomography will serve as a way to validate a humanized mouse model of COVID-19infection by comparing the quantitative changes with those in human autopsy samples. We will be comparingboth standard histological sections and histotomographic images from adjacent tissue. Machine learning willultimately allow us to automate recognition of cell types and pathological change. The proposed augmentationof our instrumentation and expertise will facilitate definitions of the ""Geometry of Disease"" across organ systems.",2020,2023,Penn State Milton S. Hershey Medical Center,655483,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2015 +C06762,3U2CTR002818-02S1,The Impact of COVID-19 on People Living with Rare Diseases and Their Families,"Abstract: The impact of the COVID-19 pandemic on people who live with rare diseases is unknown. During the past fewweeks, the principal investigators of the Rare Disease Clinical Research Network (RDCRN) have collectivelydesigned a survey that may support a longitudinal assessment of the impact of COVID-19. The DataManagement and Coordinating Center (DMCC) of the RDCRN is coordinating the effort. The data collectedfrom this survey will aid in preparation for future studies and standard of care for the rare disease (RD)community against the potential re-emergence of COVID-19. We will conduct a baseline survey and plan tocollect follow-up data later on. We will also conduct a survey targeting healthcare providers who care for RDpatients. The objectives of the research are: 1)To estimate the proportion of RD patients who have beendiagnosed with COVID-19 infection; 2)To describe the characteristics of the COVID-19 presentation and thecourse of the infection (including treatment) among patients with RD; 3)To determine whether subgroups ofpatients defined by sociodemographic variables and geographic location, with particular rare conditions orcomorbidities have been affected more frequently or have experienced increased severity of the infection; 4)To learn about the potential interaction between specific treatment regimens for rare diseases and COVID-19infection, and specifically whether certain antibiotic, immunosuppressive, or anti-inflammatory drugs areassociated with the frequency of COVID-19 infection and its severity; 5)To learn about the main concerns thatindividuals who live with RD and their families have with respect to COVID-19, and determine how the RDCRNcan respond by providing information and advice through its network of experts, its consortia, and incollaboration with patient advocacy groups; and 6)To allow follow-up for patients and families who agree toprovide contact information, and linkage of information collected in the survey with data maintained by theRDCRN for patients enrolled in RDCRN research studies. The goal is to recruit 5,000 participants but there isnot a maximum population as this survey is intended to establish a registry. The registry will be populated viaby the RD patient, parent or provider as appropriate. Collected variables include patient demographics (race,ethnicity, date of birth, gender), details about COVID-19 infection, and the impact of the pandemic on access toroutine care, special food items, and family life, including the impact of stay-at-home orders on mood andbehavior, with associated demand for professional support to cope with stress and anxiety. The data collectiontool will also be used to identify deaths among the respondents. We have implemented the data collectioninstrument in REDCap and plan to initiate enrollment by 05/01/2020. Select survey results that are deemed ofimportance by the RDCRN consortia and by the PAGs will be returned periodically to the community. We alsoplan to launch a survey targeting healthcare providers who provide care for patients with RDs. We plan torepeat the direct data collection from people who live with RDs at least once in August-September.",2020,2024,Cincinnati Childrens Hosp Med Ctr,238500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Approaches to public health interventions | Community engagement,2019 +C06763,3UL1TR002489-03S4,ICEES+ COVID-19 Open Infrastructure to Democratize and Accelerate Cross-Institutional Clinical Data Sharing and Research,"PROJECT SUMMARY/ABSTRACTWe propose a novel technical, regulatory, and cultural solution to support research on COVID-19 and establish the open infrastructure required to respond to the next pandemic: ICEES+COVID-19. The proposed work will build on the prior work that our team has been engaged withas part of the Biomedical Data Translator program ('Translator'), funded by the National Centerfor Advancing Translational Sciences (NCATS), to research and develop the Integrated Clinicaland Environmental Exposures Service (ICEES). ICEES represents a unique, disease-agnosticframework and approach to support open sharing of and research on sensitive patient data thathave been integrated at the patient and visit level with public exposures data. Importantly,ICEES has been validated in the context of our initial driving use case on asthma. We willextend this effort to instantiate an ICEES+ COVID-19 open infrastructure, focused on patients atUNC Health who have been tested (positive or negative) for COVID-19. The proposed work willleverage not only our prior Translator work, but also new work that our team has been engagedwith as part of the NCATS Center for Data to Health (CD2H) National Covid CohortCollaborative (N3C). Indeed, the North Carolina Translational and Clinical Sciences Institute(home to UNC's CTSA) was selected by CD2H leadership to lead the technical implementationof significant portions of the N3C initiative. We will adopt the N3C COVID-19 consensusphenotype for the proposed work and extend the captured data fields to include relevant datafields that were intentionally excluded by the N3C collaborative in their effort to promoteuniformity and participation, but are available via our local clinical data warehouse, such astemperature, oxygen saturation, isolation flags, and other potentially relevant clinical features(e.g., blood type). We also have partnered with investigators affiliated with the EnvironmentalPolymorphisms Registry at the National Institute for Environmental Health Sciences and will beexposing data on their registry participants. Our overall aims are to develop and deploy ICEES+COVID-19, apply ICEES+ COVID-19 to support research on COVID-19, and promotewidespread use of ICEES+ COVID-19, largely through our engagement with the Translatorprogram, CD2H N3C, and other large-scale collaboratives. A key aspect of the proposed work isthat ICEES+COVID-19 will be open source, which will allow other institutions to rapidly adoptour approach and expose their data for open analysis of COVID-19 data by a much largercommunity. Collectively, the proposed work will catalyze efforts to respond to the COVID-19pandemic and position society to be better prepared for the next one.",2020,2022,University of North Carolina at Chapel Hill,412692,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C06764,3U41HG007050-08S1,Genomic Resource Grant for the PhenX Toolkit - expansion and sustainabilityPhenX Supplement for COVID-19 Research,"PROJECT SUMMARY/ABSTRACTBiomedical science in the 21st century is a multidisciplinary and data-intensive enterprise that relies on clearspecification of research methods and results. The reproducibility of findings and the meta-analysis of pooleddata from disparate sources are both catalyzed by standard approaches to acquiring and representing data.In this context, the PhenX (consensus measures for Phenotypes and eXposures) Toolkit(https://www.phenxtoolkit.org/) is an increasingly valuable catalog of standard measures and bioinformaticstools that help investigators improve the quality and consistency of data collection and identify opportunitiesfor collaborative research. Measures in the PhenX Toolkit are selected by working groups (WGs) of domainexperts using a consensus process and criteria established by the PhenX Steering Committee (SC). Sinceits launch, PhenX has expanded beyond standard measures for genome-wide association studies (GWAS)of common, complex diseases to include domains such as Rare Genetic Conditions, Sickle Cell Disease,and Tobacco Regulatory Research.The specific aims of the proposed Administrative Supplement ""PhenX Measures for COVID-19"" are asfollows: Specific Aim 1: Develop COVID-19 Core and Specialty collections. Specific Aim 2: Develop featuresand tools for the COVID-19 page. Specific Aim 3: Establish PhenX measurement protocols for COVID-19outcomes.The crowd-sourcing approach defined here will rapidly establish COVID-19 Core and Specialty Collectionsand raise awareness of the COVID-19 measurement protocols available in the PhenX Toolkit.Body Text (nomore than 30 lines)",2020,2022,Research Triangle Institute,955000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2013 +C06765,3U24HL135691-03S3,MIS-C Program: Data Coordinating Center for the Pediatric Heart Network MIS-C Program,"PROJECT SUMMARY/Abstract: To address the knowledge gap discussed previously, NIH is initiating a national research program focused onpediatric SARS-CoV-2, COVID-19 and MIS-C. This goal of the program is to gain comprehensiveunderstanding of phenotype, natural history, outcomes, and pathobiology of MIS-C. The Program will haveseveral components including a MIS-C Cohort Study, adaptive design trials, long-term follow-up and a robustcloud-based data platform. The PHN DCC will serve to coordinate some of the components of the Program.The Specific Aims of the DCC are as follows:AIM 1: MANAGE CORE PROGRAM OPERATIONSAIM 2: MANAGE MIS-C COHORT STUDY DEVELOPMENT, LAUNCH, AND DISSEMINATION OFRESULTSAIM 3: PROVIDE SUPPORT SERVICES TO PROGRAM COMPONENTS",2020,2020,New England Research Institutes Inc,4327649,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C06766,3UL1TR002240-04S1,Michigan Institute for Clinical and Health Research (MICHR),"Project Summary: The purpose of the proposed supplement is to support MICHR's ability to contribute data to the NationalCOVID Cohort Collaborative (N3C) initiative. This National Center for Advancing Translational Sciencesupported initiative is requesting a complete dataset containing electronic health records (EHR) of COVID-19positive and tested cases. This dataset will be a separate CDM from the overall CDM, that will need to beseparately maintained, refreshed more frequently, expanded with new data components, and have institutionalpolicies revised to accommodate the innovative vision of how such data can be securely shared, combinedwith other institutions' data, and analyzed in a manner consistent with patient privacy. The curation andgovernance of this unique instance of the UM EHR will require additional effort from both MICHR staff as wellas staff outside of MICHR including the Health Information Technology & Services (HITS) team, the Office ofResearch, the Data Office for Clinical and Translational Research (DOCTR), the institutional review board(IRB), and the Office of Compliance. MICHR will take the lessons learned from tackling the unique regulatory,compliance, and governance challenges that arise from this project to create best practices related to loweringthe barriers of future projects. The N3C platform is likely to serve as a model for how future responses tonational crises can be accomplished.",2020,2022,University Of Michigan At Ann Arbor,100000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2017 +C06767,3P01HL128192-05S1,Personalized small molecule therapy for severe asthma and cystic fibrosis.,"Respiratory infection with COVID-19 (the SARS-CoV-2 virus) has become pandemic. It has significant mortalityand high morbidity, particularly among older patients. Death typically results from severe respiratory infectionleading to ARDS. To bind to cell membranes, SARS-CoV-2 requires S protein cleavage either by thetransmembrane serine protease, serine 2 (TMPRSS2), or by the cathepsin B and L (CatB/L) endosomalcomplex. TMPRSS2 can be inhibited by camostat methylate (CM), but CM is an irritant and may not be ideal forairway administration in patients with evolving ARDS. Of note, CatB/L is inhibited by endosomal alkalinizationusing ammonium chloride. As part of P01 project HL128192, we are studying the beneficial effects of airwayalkalinization in patients with asthma and cystic fibrosis. We have a drug, alkaline glycine buffer (AGB), that isbeing produced for inhalation in our P01 project. This drug has an active IND and has excellent safety data. Wetherefore tested to determine whether AGB would cause intracellular alkalinization in cultured primary humanairway epithelial cells obtained from our P01 subjects. It did; and the drug was well-tolerated by the cells in vitro(as it is in vivo). The next step is to determine whether AGB inhibits viral replication (plaque formation as afunction of multiplicity of infection [MOI]) and viral entry (PCR) in our primary human airway epithelial cultures.To do this, we are partnering with our Indiana University BSL3 virology lab (Dr.'s Gilk and Robinson) whoanticipate delivery of SARS-CoV-2 next week. Their lab has completed preparation, particularly in anticipationof this project. If in fact AGB inhibits viral replication, we would propose to discuss with the FDA the possibilitythat we could expand our IND, allowing a trial in patients at risk for respiratory distress associated with knownCOVID-2 respiratory disease. Ultimately, outcomes of this trial would be proposed to include: mortality (primary);as well as ICU length of stay and oxygen saturation index area under the curve (secondary). In the studyproposed here, we plan to accomplish three Aims. First we will test the hypothesis that SARS-CoV-2 S-proteincleavage is inhibited by human primary airway epithelial cell alkalinization using AGB. Second, we will test thehypothesis that AGB exposure prevents SARS-CoV-2 replication and cell entry in primary human airwayepithelial cells in vitro. Third, we will perform dose-response and time course experiments to determine whetherthe inhibition of SARS-CoV-2 replication and cell entry using AGB could be a realistic therapy.",2020,2021,Indiana University - Purdue University Indianapolis,140306,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Prophylactic use of treatments",2016 +C06768,3U19AI128913-04S1,Mapping Immune Responses to CMV in Renal Transplant Recipients - Transplant Supplement,"SARS-CoV-2 virus infection and associated COVID-19 disease has caused unparalleled global morbidity andmortality in previously healthy patients, with over 4 million cases and 150,000 deaths in the US alone. Olderpatients, who experience immune dysfunction associated with aging, and patients with underlying health issues,such as chronic kidney disease, have been inequitably burdened by COVID-19. Understanding correlates ofprotection against SARS-CoV-2 infection and why these immunocompromised patients apparently possessdeficiencies in generating these protective immune responses is critical to developing clinical practices for theseat-risk populations. To address this fundamental knowledge gap, this study will characterize the natural immuneresponse to SARS-CoV-2 virus infection in immunocompromised patients and determine whether immunity islong-lasting. Specifically, we will evaluate the quantity and quality of antibodies against SARS-CoV-2 and theirrelationship to frequency and functionality of SARS-CoV-2-specific T cells, therefore generating a completepicture of the adaptive immune response to SARS-CoV-2 in immunocompromised patients.To achieve our goal, we have utilized four kidney transplant centers within the University of California to establisha cohort of 2500 patients with end-stage renal disease (ESRD) awaiting transplant and 2000 renal transplantrecipients with banked pre- and post-COVID-19 pandemic sera across a highly racially and ethnically diversepopulation, of which 40% are from minority populations that have been inequitably burdened by COVID-19. Wewill screen for exposure to SARS-CoV-2 in the complete cohort of 4500 patients, enrolling 100 ESRD and 76renal transplant recipients with evidence of SARS-CoV-2-specific antibodies, based on a recent populationseroprevalence estimate of 4% in Los Angeles. We will additionally recruit matched patients without evidence ofSARS-CoV-2-specific antibodies. Antibody titer, isotype, subclass, avidity, infection neutralization and ability tointerface with cell-mediated immunity will be determined at baseline with longitudinal follow-up 3-6 month and 9-12 months later to assess longevity of humoral immune responses to SARS-CoV-2. Similarly, we will delineatethe frequency, phenotype and longevity of SARS-CoV-2-specific cellular immune responses.This study will generate an extensive repository of clinical phenotypes, outcomes, and high-dimensional bloodand urine profiling data on longitudinal samples of patients with and without exposure to SARS-CoV-2 in theCalifornia transplant population, providing an invaluable resource for the research community in understandingimmunity to SARS-CoV-2. Utilizing state-of-the-art biostatistics and computational approaches, we will integratehigh-dimensional data of humoral and cellular immune responses to develop models of combined adaptiveimmune profiles following SARS-CoV-2 exposure and assess their longevity and likelihood of protecting uponre-exposure.",2020,2021,University of California-Los Angeles,2132116,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2017 +C06769,3R01DE006014-37S1,Bacteria and Lymphocyte Suppression in Periodontitis,"We are requesting a one year administrative supplement to our RO1 grant DE006014 entitled Bacteria and lymphocyte suppression in periodontitis. The purpose of this request is to expand the scope of the grant to take advantage of recent observations made on the cytolethal distending toxin (Cdt) and apply them to advancing our knowledge of and identifying novel therapeutic pathways for preventing SARS-CoV-2 infection. Specifically, we have identified a novel role for a host cell protein, cellugyrin (synaptogyrin-2; discussed below), which plays a requisite role in the internalization and endososmal trafficking of the active subunit of Cdt, CdtB; these events are critical to toxicity. Like the internalization process utilized by exotoxins, viruses must gain entry into host cells; this process involves the interaction between viral glycoprotein, such as SARS-CoV-2 spike protein. This protein, like other viral spike proteins, provides a receptor binding domain that confers host cell specificity (e.g, ACE2) and also fusogenic function critical to merging the virus envelope with host endosomal membrane during viral entry. Recent studies have indicated that oral epithelial cells express ACE2 and may be a target for SARS- CoV-2 infection. Therefore, this study will focus on human oral-pulmonary epithelial cells lines. We propose that cellugyrin is a major component of a universal endocytic process utilized by both virus and exotoxins to achieve entry into host cells. This study will focus on the requirement for cellugyrin for SARS-CoV-2 entry into host cells. In order to contain SARS-CoV-2 infection, it is important to identify early molecular mechanism(s) that contribute to its high infectivity as these likely also represent attractive targets for therapeutic intervention. This proof-of-principle study is aimed at demonstrating a key role for cellugyrin in the pathogenesis of SARS-CoV-2 infection of cells within the oral-respiratory tract. The potential for high impact of these studies is to provide the underpinnings for developing a novel, alternative and potentially transformative therapeutic approach to mitigate SARS-CoV-2 infection. It is in this context that this study directly addresses the spirit and focus of the Notice of Special Interest (NOSI) (NOT-DE-20-022): Urgent Competitive Revisions and Administrative Supplements for Coronavirus Disease 2019 (COVID-19) as it is not only of potential high impact, but also addresses acquisition of a more robust understanding of SARS-CoV-2 pathogenesis. Moreover, the proposal addresses one of the bulleted targets of this funding announcement: examination of the role of oral/nasal microbiota and ACE2 receptor on SARS-CoV-2 infectivity and carriage in oral fluids and nasal secretions, as gateways to the spreadof infection into the respiratory tract via proof of principle studies.",2020,2022,University Of Pennsylvania,243125,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",1982 +C06770,1R21AI158169-01,EVOLVING VIRUS-SPECIFIC sACE2 MIMICS FOR COMPETITIVE INHIBITION OF SARS-CoV-2,"PROJECT Summary: The rapid spread of the highly-pathogenic, novel SARS-coronavirus 2 (SARS-CoV-2) has caused a globalhealth emergency. Thus, there is a desperate need for effective antiviral therapeutics to counteract this virus.The SARS-CoV-2 virus enters cells using the ACE2 receptor1 which binds the viral spike protein2. In itssoluble form, ACE2 (sACE2) has the potential to be used as a stable and non-immunogenic competitiveinhibitor to SARS-CoV-2 and is presently being explored in clinical trials3. Due to the potential negative sideeffects of anti-spike mAbs18, and the fact that ACE2 exhibits other biological roles4-6 including integrinsignaling regulation7,8, spike-specific receptor mimics would yield novel therapeutics for SARS-CoV-2 andpotentially other highly infectious diseases.This proposal seeks to use machine learning and directed evolution to develop high affinity, yetendogenously-inactive mimics of sACE2 in order to create rapidly implementable therapeutics to combatSARS-CoV-2 and potential corona-like viruses. This approach would allow for the generation of scalable andtranslatable biologics, and provide a platform to rapidly course-correct for potential mutations that may arisein the future. Utilizing deep-learning with UniRep49, will design and generate sACE2 variants that tightly bindthe SARS-CoV2-2 spike protein but do not cross-interact with endogenous targets such as integrins [Aim 1].Simultaneously, we will perform directed evolution to optimize spike-binding and select against variants thatbind endogenous proteins [Aim 2]. Finally, we will identify lead candidates and evaluate the tolerance andimmunogenicity of engineered sACE2 variants in mice [Aim 3]. Collectively, this proposal will develophighly-specific ACE2 receptor mimics in order to create novel antivirals with minimal immunogenicity in timeto save lives and prevent future outbreaks.10",2020,2022,Massachusetts Institute Of Technology,399346,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C06771,3P30CA046592-31S2,Targeting TMPRSS2 expression as a therapy for coronavirus infection and replication,"Coronaviruses employ two key host proteins to gain entry and replicate within cells, angiotensinconverting enzyme 2 (ACE2), an essential receptor of entry, and cell surface transmembrane protease serine 2 (TMPRSS2), a serine protease that cleaves coronavirus spike proteins following receptor binding to promote viral fusion and entry into cells. Chemical inhibitors and RNA interference of TMPRSS2 have been shown to markedly slow coronavirus entry and replication in human lung epithelial cell lines. In vivo studies with TMPRSS2 transgenic knockout mice have further shown that loss of TMPRSS2 can reduce coronavirus replication in lungs, elicit a weaker proinflammatory response, and result in milder lung pathology. Importantly, initial data stemming from studies on the novel coronavirus responsible for the COVID-19 pandemic, SARS-CoV-2, show that viral entry mechanisms appear similar to other coronavirus family members, as SARS-CoV-2 entry into cells is decreased upon TMPRSS2 inhibition. Altogether, these data strongly suggest that modulation of TMPRSS2 levels may be an effective treatment strategy for patients infected with SARS-CoV-2. The Chinnaiyan lab discovered TMPRSS2 as the androgen-regulated 5' partner of the TMPRSS2- ERG and TMPRSS2-ETS family of prostate cancer gene fusions. TMPRSS2 expression is directly regulated by the androgen receptor (AR), which has been extensively studied and targeted through various therapeutic interventions for the treatment of prostate cancer. Preliminary data from our lab suggests that lung TMPRSS2 is also androgen-regulated. Notably, several FDA-approved agents targeting AR activity in prostate cancer, such as enzalutamide, can markedly inhibit TMPRSS2 expression through antagonism of AR. We, therefore, hypothesize that FDA-approved drugs that markedly inhibit TMPRSS2 expression, like enzalutamide, may be effective in inhibiting coronavirus replication and possibly infection. Recent data from Italy (and other countries) suggests that males, who implicitly have higher levels of androgen than females, die of coronavirus by a factor of two-to-one, providing orthogonal evidence that AR activity may indeed be a player in COVID-19 progression. Thus, we would like to quickly generate pre-clinical data to support the idea that agents that suppress AR/TMPRSS2 may be repurposed to treat or prevent coronavirus infection. Based on this pre-clinical data, we would quickly assemble a clinical team to initiate a clinical trial investigating FDAapproved AR antagonists in patients infected with SARS-CoV-2. Critically, most samples for these studies are already banked in our lab to support an accelerated timeline, and since agents like enzalutamide are FDA-approved, this project could have immediate clinical impact for COVID-19 patients.",2020,2023,University Of Michigan At Ann Arbor,390000,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,1997 +C06773,3R01DK118222-03S1,Prediction of Major Adverse Kidney Events and Recovery (Pred-MAKER) in COVID-19 Patients,"PROJECT SUMMARY Major adverse kidney events (MAKE) are common in individuals hospitalized with COVID-19, particularly inthe United States. Our data from Mount Sinai show that ~40% of hospitalized patients develop acute kidneyinjury (AKI); 20% of those need renal replacement therapy, and the mortality rate in patients that experienceCOVID-19 associated AKI is several-fold greater than patients without AKI. Furthermore, we have seen thatthe rate of non-recovery is also significantly higher compared to those observed in non-COVID AKI,highlighting the potential long-term effects of SARS-CoV-2-associated kidney damage. We propose to utilizethe highly coordinated tissue and biospecimen collection machinery that has been initiated at the Mount SinaiHealth System. As the largest hospital system at the epicenter of the crisis, Mount Sinai treated anddischarged nearly 10,000 COVID-19 patients and created a central IRB approval and data coordination systemunder the auspices of the newly formed Mount Sinai COVID Informatics Center. As part of biospecimen andclinical data collation efforts, we have consented and obtained blood, urine or clinically indicated kidney biopsysamples from over 700 patients at the time of admission. Using these samples, we propose (1) to use a multipronged approach to determine the biomarkers that areassociated with MAKE; (2) to develop a machine learning-based predictive algorithm using a combination ofmultiplexed biomarker expression levels and clinical metrics; and, (3) to determine cellular pathways that areresponsible for COVID-associated AKI by combining multiomics interrogation of SARS-CoV-2 positive patienturine and kidney biopsies as well as the time-dependent transcriptomic signatures of in vitro primary proximaltubule cells. First, our results will have an immediate translational outcome, which will help focus clinical efforts on highrisk patients and triage low risk patients quicker. In addition, our proposal will lead to improved understandingof the complex disease mechanisms that cause the unique kidney injury signatures in COVID-19 and may leadto development of novel biomarkers and therapeutics that may prove beneficial during post-COVID clinicalcare. Our rigorous approach is innovative, and it is supported by established complementary assays. We haveassembled an experienced multidisciplinary team encompassing bioengineers, nephrologists, basic scientists,informaticians and virologists that will help improve the understanding of the landscape of kidney outcomesduring COVID-19 hospitalizations.",2020,2023,Icahn School Of Medicine At Mount Sinai,468762,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2018 +C06774,3R01AI135803-03S2,IMPACC-MEDVAMC,"The objective of this supplement proposal is to understand the causes of airway diseases and thereby improvediagnosis and therapy of these common and debilitating of human ailments. The ImmunophenotypingAssessment in a COVID-19 Cohort (IMPACC) study coordinates a national, multi-institution consortium,collecting detailed clinical data and biologic samples from hospitalized COVID-19 infected individuals, with thegoal of identifying immune signatures/molecular biomarkers associated with clinical disease course, to allowthe prioritization of clinical interventions and decision making. This supplement supports Baylor College ofMedicine's and the Michael E. DeBakey VA Medical Center's (MEDVAMC) participation in IMPACC to facilitatescreening and enrollment of inpatients with COVID-19. The proposed supplement research is within the scopeof parent grant R01 AI135803, Fungal Pathogenesis of Moderate to Severe Asthma. This supplement issubmitted for the purpose of Clinical data and sample collection/processing and the scope will be confined topatients confirmed to have COVID-19. Based on projected trends in COVID-19 disease in MEDVAMC, weestimate that up to 50 COVID-19 patients can be enrolled within 6 months. As enrollees will be followed for upto one year, the budget extends to 18 months. Data to be collected will consist of both primary and secondaryclinical and mechanistic endpoints as well as exploratory clinical and mechanistic endpoints.",2020,2022,Baylor College Of Medicine,162902,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +C06775,3U45ES006175-31S1,Training At-Risk Workers on the Corona Virus and Bio Safety Hazards (2),"In response to the COVID-19 pandemic that has swept the country, the USW Tony Mazzocchi Center and its training partners will use their decades of experience in health and safety training including infectious disease to provide information and support to workers and community members. The program is designed to provide information on disease transmission and controls necessary to reduce its impact. Additionally, because physical distancing has become part of the ""new normal"", this program will include support for each of the training partners to equip themselves to conduct training using both online and blended formats. These modalities differ from the face to face training typically conducted under our programs. The change in approach will require both technological upgrades and a new way of sharing material. The three parts of this program include: Training and Outreach: -Produce and conduct web-based training on COVID-19 and its effect on workplaces and communities -Produce and conduct Spanish language trainings on COVID-19 Developing and Deploying Advanced Technology: -Support online training platforms for the TMC and its training partners -Purchase of software or licenses -Purchase of training tools that support distance learning Strengthening the Special Emergency Response Training (SERTs) Program: -Onboarding four additional worker trainers to the SERTs team -Initial training on relevant topics concerning HAZWOPER and COVID-19.",2020,2025,Steelworker Charitable/Educational Org,250000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,1992 +C06776,3R01HL149450-02S1,Effects of donor plasma and recipient characteristics on convalescent plasma treatment outcome of COVID-19,"In the absence of FDA-approved pharmacological therapies, convalescent plasma infusion has rapidly emerged as a notable emergency therapy for severe cases of COVID-19. However, due to the emergency conditions under which this treatment has been practiced, little effort has been placed in characterizing the properties of the donor plasma and the clinical status of the COVID- 19 patients that can most benefit from the infusion. We have assembled a multidisciplinary team that leverages linked blood donation and blood transfusion programs at Robert Wood Johnson University Hospital and state-of-the-art resources for the study of antibody responses and plasma markers of COVID-19 severity. This team proposes to conduct a study that relates donor plasma properties (antibody titers and functions, and antigen targets) and recipient's clinical status (including peripheral blood cell immunophenotypes and various plasma markers of COVID-19 severity) to the success of convalescent plasma infusion. The new knowledge resulting from our plan will guide the development of rational clinical practice guidelines and the design of convalescent plasma clinical trials.",2020,2021,Rutgers The State University of New Jersey,753853,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Prognostic factors for disease severity | Supportive care, processes of care and management",2019 +C06777,3R35HL135756-04S1,Pneumonia Biology,"Project Summary COVID-19 is a pressing crisis. The responsible coronavirus, SARS-CoV-2, is highly infectious, spreads rapidly, and causes severe disease requiring hospitalization, critical care, or mechanical ventilation. However, even for SARS-CoV-2, only a minority of cases are severe. The biological factors determining who gets very ill need to be better understood. Severe COVID-19 involves pulmonary pathology demonstrating diffuse alveolar damage, hyaline membranes, and inflammatory infiltrates containing T cells and macrophages. While T cells are prominent in the diseased lung, diminished circulating T cells associates with poor outcome. Previous severe coronavirus diseases, SARS and MERS, provide mechanistic perspective. SARS and MERS also have lymphopenia and damaged lungs containing T cells and macrophages, and for these infections inhibiting T cells, antibodies, or monocyte-macrophages can diminish severity of disease. Whether, when, which, and why immune activities may be contributing to lung damage in subsets of COVID-19 patients are unclear. For many respiratory pathogens, heterotypic immunological memory is pivotal to the outcome of infection, but there are no data about whether this applies to coronaviruses. Four coronaviruses (OC43, HKU1, 229E, and NL63) circulate regularly and are among the most common causes of colds and pneumonias. The types of immune memory arising after infections with these viruses is uncertain, and whether or how heterotypic immune memory influences SARS-CoV-2 infections constitute a crucial knowledge gap. Heterotypic immune memory is helpful for fighting influenza viruses, RSV, and pneumococcus. However, pre-existing immunity could be detrimental instead and drive disease, which seems plausible for COVID-19 based on coronavirus epidemiology, immunology, and pathophysiology. We hypothesize that a recent coronavirus infection makes an individual susceptible to more severe COVID-19. We also recognize that the opposite may be true, and recent prior human coronavirus infection might instead provide heterotypic protection against SARS-CoV-2 and thereby make COVID-19 less severe. Either way, the question demands an answer. The effects of pre-existing heterotypic immunity on immune responses and lung defense during subsequent infections is the focus of the ""Pneumonia Biology"" NHLBI R35 award. To effectively and expeditiously study SARS-CoV-2 in containment facilities, including effects of a prior human coronavirus challenge, we created new collaborations and propose to perform studies that will be a change in scope and lead to this Competitive Revision to the R35. Whether and when an individual has been recently infected by other coronaviruses may be a major determinant of COVID-19 severity. We propose to answer this question, with studies expressly designed to minimize time needed while maximizing relevance and impact. Our goal is to provide this answer quickly, for informing and improving the medical and public health approaches to COVID-19.",2020,2021,Boston University Medical Campus,716519,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2017 +C06778,3R01AI150246-02S1,Small Molecule Screening to Identify Novel Sars-CoV-2 Therapeutics,"Summary: The current outbreak of the coronavirus in China (SARS-CoV-2) has spread rapidly. There are experimental drugswhich will be tested; however, there are no approved therapeutics or vaccines. Indeed, there are tests underway todetermine whether remdesivir, which was developed against filoviruses, can be repurposed against SARS-CoV-2infection. It would be transformative if we could identify additional small molecules that could be repurposed to treatthe outbreak of SARS-CoV-2 infection. Given that the goal of the parent grant (R01AI150246) is to discoverantivirals active against bunyaviruses, based on findings from cell based screening, and that we have broadexpertise in diverse viruses, we are applying for Supplemental funding (notice number NOT-AI-20-030, PA-18-035)to expand the scope of the existing grant to use the same methods (small molecule screening) to identify antiviraltherapeutics active against SARS-CoV-2 infection. We will screen two libraries of known bioactives to potentiallyrepurpose existing therapeutics. First, we will test a library of innate immune agonists (~100 PAMPs) for their abilityto block SARS-CoV-2 infection in human cells including airway cells. Second, we will screen another 'actionable'library that I have created as the Director of the High-throughput Screening core at UPENN. We created a library of~3000 drugs that includes ~1500 FDA approved compounds, ~1000 drugs in clinical trials and the remaining drugshave known targets. This library has been used for repurposing (as is being done with the Gilead drug remdesivirthat was originally developed against filoviruses) to more rapidly identify active therapeutics for future testing inhumans. We will also determine if any of our active antivirals act synergistically with remdesivir since this drug iscurrently under development for use against COVID-19. We expect to identify additional drugs with activity againstSARS-CoV-2.",2020,2022,University Of Pennsylvania,336020,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C06780,3R01AA027496-02S1,"COVID-19 Pandemic-related Impacts on Longitudinal Trajectories of Alcohol, Marijuana, and Simultaneous Use and Mental Health Among Young Adults","Abstract: The devastating impacts of the COVID-19 pandemic will likely include negative consequences for youngadults' (YAs) mental health and substance use. It is important to know how alcohol, marijuana (MJ), andsimultaneous use of both substances (i.e., simultaneous alcohol and marijuana [SAM]), as well as motives foruse may be changing in response to COVID-19. The cumulative impact of multiple financial, housing,employment, and social disruptions or losses during the pandemic has the potential to have unprecedentednegative effects on alcohol and MJ use as well as mental health among YAs. In particular, the ability toexamine variation in trajectories of alcohol and MJ use starting from years prior to onset of COVID-19 andextending through the acute pandemic period and beyond is important to guide better prediction models foralcohol and MJ use behavior in times of crisis, including whether trajectories may diverge as policy implications(e.g., stay at home orders) may influence availability, motivations, and mental health. Documenting risk andprotective factors associated with YAs' risk for increased or problematic use during or in response to thepandemic will make it possible to identify those in greatest need of interventions and/or identify targets forintervention during other large-scale crises. The proposed project will supplement R01AA027496 by extendingan existing longitudinal study of 600 diverse young adults (ages 22-29) who participated in Project Transitions(enrolled 2015/2016) and were followed for 24 consecutive months and completed 30-month follow-up.Participants were most recently surveyed in January 2020 (pre-pandemic) and April 2020 (at the height of theacute phase of COVID-19). Using a randomized staggered design, respondents of the January/April surveyswill be invited to complete six bi-monthly surveys between July 2020 and June 2021. The randomizedstaggered design allows us to capitalize on our prior longitudinal intensive monthly design and track relevantvariables cost-effectively across one year as this dynamic public health crisis continues to evolve. Data from 3-5 years pre-COVID with detailed information about transition experiences, substance use, and mental healthwill be combined with new assessments during and after the acute COVID-19 pandemic. Specific aims will beto examine: (1) ) impact of the pandemic and related policies (e.g., stay-at-home order) on YAs' social roletransitions during the acute pandemic and subsequent year and concurrent associations between social roletransitions and alcohol, MJ and SAM use; (2) how physical distancing and economic changes over the courseof the pandemic are associated with shorter- and longer-term alcohol and MJ use and problems (includingAUD/CUD) and motivations for use; (3) impact of the pandemic on longitudinal trajectories of YA alcohol andMJ and SAM use (including whether the pandemic led to substitution [i.e., increases in one substance] orcomplementary effects [i.e., increases in both substances] of alcohol and MJ), and changes to motivations foruse (i.e., social and coping motives) and mental health (i.e., anxiety, depression); and (4) who is most at risk.",2020,2022,University Of Washington,118048,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C06781,3P30CA225520-03S3,Mobile Health Study and Chemoprophylaxis for Preventing Severe Illness from COVID-19 in Cancer,"The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) outbreak in late 2019 has resulted in approximately 1.4 million confirmed cases of novel coronavirus disease (COVID-19), with 85,522 confirmed deaths worldwide. The United States has recently taken the lead with the most reported cases across the world, with a total of 395,030 new cases and 12,740 attributable deaths as of today, April 9, 2020. Severe disease occurs in ~10% of cases overall. However, risk for severe disease and mortality is greater in immunocompromised cancer patients, requiring scarce ventilation resources and intensive care unit space to address rapid clinical deterioration in this population. We propose to use the established InsightTM mHealth Platform (supported by the Stephenson Cancer Center (SCC) mHealth Shared Resource) to monitor symptoms that are consistent with early signs of infection in this high-risk population and automatically (and securely) transfer this information to health care providers. Further, we aim to determine if antimicrobial prophylaxis can mitigate the severity of disease resulting from SARS-CoV-2 infection in cancer patients. Specific Aims: 1. Rapidly deploy a smartphone-based assessment and intervention tool that will enable actively treating cancer patients (N=500) to monitor and self-report symptoms and disease exposures in real-time. The InsightTM app will be downloaded onto the smartphones of patients undergoing cancer chemotherapy. Standard COVID-19 screening questions and a single chemotherapy risk question will be assessed daily through the smartphone app. Specific responses will automatically trigger an alert to clinic nurses AND provide app-based access to contact the clinic for triage to home care or emergency assessment. 2. Initiate antimicrobial prophylaxis in patients that indicate two symptoms or one symptom with exposure to COVID-19 in advance of or concomitant with SARS-CoV-2 testing. When emergent medical intervention is not required, patients will be randomized to standard supportive care or antimicrobial prophylaxis with hydroxychloroquine and azithromycin and will use the app to report daily changes in symptoms. 3. Collaboratively document and share lessons learned regarding the impact of the COVID-19 pandemic on cancer care delivery via telemedicine. We commit to a collegial collaboration with other cancer centers funded to study the use of telemedicine through the COVID-19 CCSG supplement mechanism. This study will determine if an app can be used to rapidly report SARS-CoV2 symptoms, and if antimicrobial prophylaxis reduces severe morbidity and mortality of SAR-CoV2 in immunocompromised cancer patients. The potential reduction of severe COVID-19 mediated disease through: 1) reducing time from symptom detection to treatment initiation, and 2) use of antimicrobial prophylaxis with the repurposed agents listed above. The mHealth platform will be used to monitor symptoms in real-time and facilitate medical triage of high-risk patients. Antimicrobial prophylaxis will further decrease the incidence of COVID-19 mediated morbidity and mortality.",2020,2023,University Of Oklahoma Hlth Sciences Ctr,217000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Clinical trials for disease management | Prophylactic use of treatments,2018 +C06782,3R44TR003065-02S1,Organ-on-Chip Approach for Assessing Tissue-specific SARS-CoV-2 Infection and Response to Antiviral Therapy,"The current COVID-19 pandemic is a worldwide, rapidly developing, health crisis caused by the Severe AcuteRespiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of May 18, 2020, over 4.7 million infections areconfirmed globally and over 315,000 people have died from COVID-19 related complications. Efforts to developand test COVID-19 vaccines are in high gear. In the meantime, there is a dire need for fast and robust in-vitrotests that can be used to study the mechanisms of host-virus interactions and help assess whether existingantivirals could be used against for SARS-CoV-2. Current static 2D cell culture systems and animal-basedmodels are of limited use for these purposes. To address this gap, the proposed project aims to develop organ-on-chip (OOC)-based assays for quantifying SARS-CoV-2 inoculation and replication in three human tissuesthat have been shown to be severely affected by SARS-CoV-2. In order to enable an immediate start, a fasttimeline, and milestones with translational impact, the approach of this supplement will mainly repurpose alreadyexisting, validated, and commercialized OOC models that were developed under the parent grant. AIM1 is todevelop SARS-CoV-2 assays for kidney proximal tubule and vascular endothelium, models that were initiallydeveloped for assessing drug toxicity and drug transport. In addition, an OOC model of the lung alveolus will bedeveloped. SARS-CoV-2 Wuhan Reference Strain, the SARS-CoV-2 Spike Mutation D614G Strain, as well asa Spike-pseudotyped lentivirus will be tested and compared for differences in inoculation rate and replicationrate (AIM2). The assay protocols will include introducing the viruses via the perfusate to the lumen of the tissuestructures in order to bring the virus in contact with the ACE2 and CD 147 receptors that reside on the apicalside of the cell and are responsible for virus binding and subsequent endocytosis. To quantify viral inoculation,the tissues will be removed after a short but adequate incubation period. The viruses will be extracted from thetissues, serially diluted and quantified using plaque assays. In order to assess viral replication, tissues will beharvested from the chips after a pre-determined, longer, incubation period that gives the cells enough time forviral replication. Viral load will be quantified with plaque assays. AIM3 is to use the OOC-based assays for testinga number of candidate antivirals and compare their effect against baseline SARS-COVID-19 virus load. The listof antivirals to be tested includes antibodies against ACE2 and CD147 receptors; RNA polymerase inhibitorRemdesivir; PAMP RNA, a RIG-agonist and interferon inducer; and the antimalarial chloroquine. The dataobtained from the OOC assays will be correlated with pre-existing in-vitro data, animal data, and clinical findings.The technology can be quickly made available to the research community. Models of other tissue structuresaffected by SARS-COVID-19, such as myocardium, intestinal mucosa, and kidney glomerulus can besubsequently added to the portfolio. Further, the models can be tailored to include cells from elderly patients ormimic conditions connected with severe outcomes, such as diabetes, hypertension, or kidney disease.",2020,2022,Nortis Inc,255716,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Prophylactic use of treatments,2019 +C06783,3U45ES019350-11S1,Project SEAMIST (South East Area Maritime Industry Safety Training),"Project SEAMIST, a WTP awardee with primary responsibility for the training of workers in themaritime industries and community for hazardous chemical safety and response, proposes toprovide this essential worker community with critical training in awareness and safe workinghabits in response to the current COVID19 outbreak. Project SEAMIST will deliver, viaestablished, facilitated online procedures, COVID19 training, as developed and provided by theNIEHS WTP, with local optimization and adaptation for our maritime clientele. ProjectSEAMIST has identified a marketing agent, Resolve Maritime Academy, and client industriesincluding ship and port workers, warehouse employees and freight forwarders, who haveexpressed a need for such training. In addition, Project SEAMIST has identified an expertcollaborator, Dr. Alex Isakov, previously leader of a WTP infectious diseases program, to act asa subject matter expert and facilitator in the delivery of this training. Dr. Isakov's program waslargely performed online, and while Nova Southeastern University has extensive experiencedelivering online learning, we welcome Dr. Isakov's input into trainings in this critical subject.",2020,2021,Nova Southeastern University,200000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2010 +C06784,3R01NS112511-01A1S1,COVID-19 Neurological Georgia Cohort Study,"The SARS-CoV-2 virus, like other coronaviruses, is neurotropic. A clue to early invasion and involvement of thenervous system in COVID-19 patients are the early symptoms of anosmia and hypogeusia. These may be seenin over 60% of COVID-19 positive patients. There is evidence from the humanized ACE2 transgenic mouse thatthe SARS-CoV-1 virus rapidly invades the olfactory bulb and spreads transneuronally throughout the olfactorypathwaysOur overall goal is to determine if there are long term neurological sequelae to SARS-CoV-2 viral infection inboth asymptomatic and symptomatic COVID-19 positive patients and to understand the contributing health andgenetic factors. To achieve this goal, we will establish a longitudinal prospective cohort of COVID-19 positivepatients and follow them long-term for neurological sequelae. COVID-19 preferentially affects African Americans(AA) and we will be enrolling in the Central Savannah River Area (CSRA) of Georgia where we expect abouthalf of our patients to be AA. Our hypothesis is that long term neurological sequela will occur over timein COVID-19 positive patients and there will be clinical, racial and genetic predictors of occurrence andseverity of neurological sequelae. To test this hypothesis, we will recruit 500 COVID-19 positive patientsat baseline and conduct follow-up annually. The specific aims are:Aim 1: Determine if COVID-19 positive patients have an increased risk to develop neurological complicationsand cognitive impairment over time and if there is disparity in occurrence and severity of complications in AA.Aim 2: Determine the relative contributions of pre-existing comorbidities, the initial clinical presentation (e.g.,anosmia) and genetic contributions to the development and severity of neurological complications.The technical goal of Year 1 is to recruit 500 COVID-19 positive patients for the baseline testing and conductyear 1 follow-up. The specific aims for Year 1: Aim 1. Determine the 1-year incidence rates of persistentanosmia, hypogeusia and neuropsychiatric disorders (i.e. cognition, depression and anxiety) and whether thereare differences between gender, ethnicity and age groups; Aim 2. Identify the potential contributing factors (i.e.severity of the COVID-19, pre-existing health conditions, the initial clinical presentation of neurological symptomsand unhealthy lifestyles including smoking and use of alcohol and illegal drugs) to the 1-year incidence ofpersistent anosmia, hypogeusia and neuropsychiatric disorders.",2020,2021,Augusta University,308000,Human Populations,Black,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C06785,3U54GM104942-05S2,West Virginia Clinical and Translational Science Institute: Improving Health through Partnerships and Transformative Research,"Emergence of a novel coronavirus, now known as severe acute respiratory syndrome coronavirus2 (SARS CoV-2), has resulted in human disease (COVID-19) that has swept the globe inpandemic proportions with more than eight million confirmed cases and >440,000 deaths to date.Surges of COVID-19 have occurred throughout the United States (US) with urban centers suchas New York City and New Orleans hardest hit. COVID-19 clinical descriptions have evolvedfrom what was initially felt to be a respiratory illness to a multisystem disease with proteanmanifestations. Moreover, disparities in outcomes have been described with African Americanshaving higher infection and mortality rates. Populations residing in rural areas are often poorer,older, and have multiple co-morbidities such as type 2 diabetes, obesity and hypertension, raisingquestions about disease manifestations and outcomes that may differ from those described inurban areas. COVID-19 cases and mortality in rural areas continues to climb with multipleoutbreaks, many of which have been related to meat packing plants and prison clusters. TheNational COVID Cohort Collaborative (N3C) has been established by the National Center for Datato Health (CD2H) in partnership with the National Center for Advancing Translational Sciences(NCATS) for purposes of building a centralized national data resource for the study of COVID-19.As N3C will facilitate translation of data into knowledge urgently needed to effectively address theCOVID-19 pandemic, it is critically important that this resource contain patient outcomes datafrom diverse populations throughout the US - both urban and rural - with inclusion of populationsof color, Native Americans, and others. The Institutional Development Award Program ClinicalTranslational Research Centers (IDeA CTRs) are located in diverse areas of the US, serving ruralpopulations as well as other vulnerable groups, including Native Americans and persons of color.IDeA CTRs are well poised to provide outcomes data that relate to a diverse group of medicallyunderserved persons that may otherwise not receive adequate representation in the N3C.Specifically, eight IDeA CTRs located in Delaware, Louisiana, Maine, Mississippi, Nebraska,Oklahoma, Rhode Island, and West Virginia have established relationships with healthcareorganizations that have, to date, have conducted SARS CoV-2 testing among more than 285,000persons, of whom more than 25,000 have tested positive. This project will enable rapidcontribution of COVID-19 patient data from IDeA states to N3C, enhancing understanding ofCOVID-19 in the US and driving further research addressing COVID-19 patient outcomes inmultiple underserved populations.",2020,2022,West Virginia University,1573155,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Health information systems,2012 +C06786,3R21AA026689-02S1,Developing a Prevention Model of Alcohol Use Disorder for Pacific Islander Young Adults,"Abstract This administrative supplement proposes to re-survey Pacific Islander young adults from our parent R21 tounderstand their unique alcohol risks and harms during, and in response to, the COVID-19 pandemic.Specifically, we will survey 18-30-year old young adult participants in two large Pacific Islander communitiesthat have been deeply affected by the COVID-19 crisis: Samoans in Los Angeles County and Marshallese inNorthwest Arkansas. In prior R21 data collected from these participants, we determined that Pacific Islander young adults are atexceptional risk for alcohol misuse and related harms with an alarming 56% of participants screening positivefor hazardous drinking, 49% for alcohol use disorder, and 40% experiencing significant alcohol-related harms.It is in this context of elevated alcohol burden and high-risk drinking that community concern has emergedregarding the potential negative impact of the COVID-19 pandemic on Pacific Islander young adults' alcohol-related behaviors and health outcomes; as many work in high-risk settings such as meat-packing factories-the number one source of COVID-19 outbreaks in the U.S. The specific goals of this research are to (1) assess Pacific Islander young adults' COVID-19-relatedknowledge and risk of exposure, and (2) re-assess their alcohol use, misuse, comorbid substance use, andalcohol-related harms. Using remote survey methods designed to assess substance use in Pacific Islandercommunity populations, the information gathered in this study will allow us to explore participants' datalongitudinally to understand the scope of Pacific Islanders' exposure to COVID-19-related (1) healthchallenges, and (2) changes in Pacific Islanders' alcohol use and associated harms. The findings of this studywill be disseminated to Pacific Islander stakeholders and response teams to support ongoing communityefforts to increase public awareness of Pacific Islander health disparities during this urgent health crisis.",2020,2021,University Of California-Riverside,89910,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2018 +C06787,3R01DK119936-03S1,"Impact of a SARS-CoV-2 vaccine on gut integrity, immune activation and efficacy of ART","Abstract: A coronavirus pandemic is currently in progress and a tremendous effort for developing effective vaccines to curbit is currently being made. Adenovirus (Ad)-based vaccines are in the lead in the clinical trials, and it is to beexpected that at least one vaccine formulation will comprise of an Ad vector. These vectors are known for inducingmassive activation of the immune responses at the mucosal sites. The gastrointestinal (GI) tract is the primary siteof HIV replication and CD4+ T cell depletion. HIV induces major alterations at the mucosal sites, which impact theirbarrier function, permitting transfer of microbial products from the intestinal lumen into the surrounding tissues andgeneral circulation. Microbial translocation is a key driver of the chronic immune activation and inflammation(IA/INFL) that are responsible for HIV disease progression. IA/INFL have a tremendous impact on the outcome ofHIV infection and persist even in subjects on antiretroviral therapy (ART), preventing a proper recovery of the CD4+T cells and thus being responsible for comorbidities and accelerated aging. Improving gut health and controllingchronic IA/INFL is thus one of the major goals both for prevention of HIV-associated comorbidities and for curestrategies. It is conceivable that the use of Ad-based vaccines for the SARS-CoV-2 in people living with HIV mayresult in high levels of IA/INFL at the mucosal sites, which may reverse HIV control provided by ART. Therefore,we teamedwith Dr. Andrea Gambotto from the University of Pittsburgh, who produced a recombinant type 5 Advector encoding the transgene for the antigen SARS-CoV-2 S1 subunit (Ad5.SARS-CoV-2-S1). We will use thisvaccine in SIV-infected, ART-suppressed rhesus macaques (RMs) to induce effective mucosal immune responsesto SARS-CoV2, and we will monitor the impact of these responses on the key pathogenic features of HIV infection:(a) T-cell immune activation, with particular attention given to the mucosal sites; (b) mucosal inflammation and gutintegrity; (c) microbial translocation; (d) microbiome; (e) hypercoagulability; (f) impact on the drug metabolism andviral suppression; (g) impact on the viral reservoirs. Since severe SARS-CoV-2 infection disproportionately targetolder individuals, both young and old RMs will be included. Our specific aim is to test the impact of a SARS-CoV-2 vaccine on the gut dysfunction and its consequences, systemic immune activation and inflammation andon the response to ART and viral reservoirs in ART-suppressed SIV infection of young versus old RMs. By directly probing the impact of an Ad5.SARS-CoV-2 S1 vaccine on key parameters of HIV infection, ourapproach will assess whether the planned COVID-19 vaccination has the potential of being deleterious to HIV-infected subjects. We will also assess the importance of a healthy gastrointestinal mucosa to the efficacy of theSARS-CoV-2 vaccine, which goes beyond the HIV infection field, covering all the inflammatory bowel diseasepathology.",2020,2022,University Of Pittsburgh At Pittsburgh,705280,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2018 +C06788,3U45ES014084-16S1,International Brotherhood of Teamsters Hazardous Materials Worker Health and Safety Training,"International Brotherhood of Teamsters Consortium (IBT Consortium) developed a Biosafety Preparedness training program in response to the COVID 19 pandemic. In preparation to deliver training to front-line workers, the IBT Consortium is updating its course curricula concerning blood-borne and other infectious diseases that may affect the target populations. To ensure fiscal accountability and sound management practices, the IBT Consortium uses a comprehensive management and administrative structure that provides for multiple levels of review for program expenditures and activities.",2020,2021,International Brotherhood Of Teamsters,300000,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2005 +C06789,3R01DK124063-01S1,Role of Kidney Proximal Tubular Secretion in Critical Illness,"PROJECT Abstract: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2). SARS-CoV-2 has been identified within multiple cell types of the kidneys,including tubular epithelial cells, endothelial cells, and podocytes, suggesting pathologic effects. Early clinicaldata suggest a greater incidence and severity of acute kidney injury (AKI) in persons who have COVID-19;however, existing studies lack comparisons with similarly ill persons who do not have COVID-19, preventingreliable assessment of the causal impact of SARS-CoV-2 on kidney injury and function.Most underlying causes of AKI involve injury to tubular epithelial cells and their microenvironment. Yet, theprevailing clinical assessment of kidney function in AKI is based on incremental changes in serum creatinineconcentrations under the assumption that glomerular filtration and tubular functions are tightly coupled withinan individual. To challenge this assumption, our parent NIDDK funded grant, ""Role of Kidney Proximal TubularSecretion in Critical Illness"" (R01DK124063, PI Kestenbaum) is recruiting a prospective cohort of critically illadults without COVID-19, quantifying tubular secretory clearance using a novel assay that we have developed,and determining the impact of this intrinsic kidney function on prognosis and kidney drug dosing.In this supplement, we propose to expand the unique tools of the parent grant to delineate the impact of SARS-CoV-2 on the kidney tubules. To accomplish this goal, we will comprehensively characterize kidney tubularfunctions in the Covid-19 Host Response and Outcomes (CHROME) study, an ongoing prospective study ofcritically ill persons with COVID-19 that includes a comparison group of similarly ill persons without COVID-19.To our existing measurements of tubular secretory clearance, we will add markers of tubular synthesis, distaltubular viability, and tubular injury. We will test whether COVID-19 is associated with changes in these tubularprocesses over the course of hospitalization and with persistent kidney dysfunction at 30-day follow-up.",2020,2024,University Of Washington,500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts,2020 +C06790,3U01DK119083-03S1,DFU Clinical Research Unit,"Abstract: The ongoing COVID-19 pandemic disproportionately affects type 2 diabetes (T2D) patients, who are especiallysusceptible to SARS-CoV-2-induced adverse outcomes and complications. T2D patients have severalcomorbidities that increases their vulnerability: obesity, chronic inflammation, and vascular complications, i.e.,diabetic kidney disease (DKD), diabetic neuropathy (DN), and cardiovascular disease (CVD). T2D patients arealso predisposed to the cytokine storm syndrome (CSS), an acute inflammation state triggered by COVID-19.CSS releases a cascade of inflammatory cytokines that causes dangerous hyperglycemic surges andperpetuates a vicious cycle of cytokine release. Yet, there is a critical knowledge gap on how the initial CSS thatoccurs with the onset of COVID-19 disease superimposes on chronic T2D inflammation to contribute to adverseoutcomes and what are the cytokines that most strongly predict the clinical course in COVID-19 T2D patients.Given the T2D prevalence, high COVID-19 infection rate, and lack of therapies, there is an urgent unmet needto identify risk-factors and inflammatory biomarker profiles that predict the most critical incoming COVID-19 T2Dcases to prepare us for the next pandemic wave.We also urgently need evidence-based guidelines for managingcomplications in survivors from the first wave. Our objective is to establish the knowledge base needed to meetthis clinical need by developing risk-assessment tools to inform management of current COVID-19 T2D patientsand prepare for future waves. Our overall hypothesis is that acute inflammatory surges, secondary to SARS-CoV-2-induced CSS, raise the risk of acute adverse outcomes and accelerate progression of chronic diabeticcomplications. We will test this hypothesis in an ongoing cohort of ~500 severe COVID-19 patients admitted atMichigan Medicine, of whom 208 have T2D. Known as the Michigan Medicine COVID-19 Cohort (M2C2, PI:Hayek), clinical data and biosamples were collected on admission and throughout the hospital course. Our one-year short term goals are to: (i) identify inflammatory signatures that correlate to inpatient outcomes in the M2C2,(ii) deeply phenotype M2C2 participants 3-6 months post-hospitalization for chronic vascular complications (DKD,DN, CVD), and longer term inflammatory signatures, (iii) assess the 3-6 month psychosocial outcomes of M2C2participants. Our Specific Aims are:1) Identify an inflammatory biomarker signature linked to acute complicationsin T2D M2C2 patients; b) Define the post-discharge clinical course by inflammatory biomarker signatures in T2DM2C2 patients. Our proposed research will have immediate significant impact by generating the knowledge basedrequired for much needed, and immediately applicable clinical guidelines for managing current and futureCOVID-19 T2D patients. It will also establish an informative biomarker panels that correlate with acute andchronic T2D COVID-19 clinical phenotypes and inform outpatient management of T2D patients post-COVID-19infection. Data from this proposal are urgently needed to treat our T2D population in light of their particularvulnerability.",2020,2022,University Of Michigan At Ann Arbor,388652,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts,2018 +C06791,3U54CA210181-05S1,Targeting the Inflammasome As a Treatment Strategy for COVID-19 infected cancer patients,"The novel coronavirus SARS-CoV-2 or COVID-19 has infected over a million people with approximately 63K deaths in the United States alone (date: April 30, 2020). While little is known about this coronavirus, COVID-19 is known to initiate pathologic inflammation characterized by elevated ferritin and d-dimer, and proinflammatory cytokines such as interleukin (IL) -2R, 6, 10 and Tumor Necrosis Factor-alpha (TNF-Į), suggesting that mortality might be due to organ failure driven by hyperinflammation. Cancer patients with COVID-19 infection are at about 3.5 times increased risk of developing severe cases and requiring hospitalization, as has been observed at our Houston Methodist Hospital (HMH) and a published report on patients in Wuhan, China. This administrative supplement is designed to gain in-depth insights onto the immune response of cancer vs. non-cancer COVID-19 patients undergoing pilot therapeutic interventions at HMH that has received very positive clinical outcomes: 1- the use of tocilizumab, an anti-IL-6 receptor antibody (Actemra, Genentech, South San Francisco, CA); and 2- a pilot study of applying Single Donor Banked Bone Marrow Mesenchymal Stromal Cells (MSC) for the Treatment of SARS-CoV-2 Induced Acute Respiratory Failure. We propose to determine the inflammation-related markers and cytokine profiles in COVID-19 infected patients following either anti-IL6 receptor tocilizumab antibody or MSC treatments and to establish correlative immune profiles to predict patient eligibility and clinical outcome. Our group is uniquely poised to conduct this study as we have access to more than a thousand samples of blood specimens (plasma and buffy coat cells) from COVID-19 cancer and non-cancer (control) patients. We believe this will help understand the ongoing processes related to both the immunological response in cancer patients affected with the viral infection and how the management of the disease affect that response and ultimately help develop immunotherapies in COVID-19 infected cancer patients.",2020,2021,Methodist Hospital Research Institute,161500,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Immunity | Prognostic factors for disease severity | Supportive care, processes of care and management | Pre-clinical studies",2016 +C06792,3P30AG049638-05S2,Conserved Transcriptional Response to Adversity (CTRA) and COVID-19: Role of Pre-existing Neighborhood Characteristics and Cognitive Impairment,"Bateman et al., NOT-AG-20-022 2020PROJECT Summary: The proposed administrative supplement will fund an investigation of the impact of COVID-19 on participants ofthe Wake Forest Alzheimer's Disease Research Center (ADRC). We will determine the impact of COVID-19related social distancing and stress on individuals with cognitive impairment as compared to older adults withnormal cognition in the WF ADRC center cohort. The proposed supplement will be conducted in the ClinicalCore cohort of the ADRC at Wake Forest School of Medicine, and falls within the general scope of the ADRCof identifying factors that modulate cognitive decline in aging and Alzheimer's disease, and synergizes with ourcenter's focus on health disparities by utilizing a metric of neighborhood disadvantage. The proposal is basedon evidence that loneliness and stress are associated with cognitive decline and are expected to be moreprevalent as a result of social distancing public health measures for the prevention of COVID-19 spread.Several prior studies have shown that loneliness is associated with chronic stress in older adults, and thatloneliness is further associated with cognitive decline, with some suggestion of a bidirectional relationship.Loneliness has been shown to be affected by neighborhood variables as well. Our proposed supplement willexamine the impact of COVID-19 on loneliness and stress, and determine whether participants with pre-pandemic cognitive impairment, or those living in more deprived neighborhoods, are more vulnerable to theimpact. There are two parts to our proposed study: a telephone-based questionnaire visit and dried blood spotcollection for transcriptional analysis. We will collected two questionnaires focused on the impact of COVID-19,as well as questionnaires to assess perceived stress, loneliness, coping strategies, and psychological well-being. Each participant will be geocoded and their area deprivation index will be obtained based on publically-available data. A new collaborative relationship has been established with the UCLA Social Genomics Corewhich will perform the RNA extraction and analysis.1",2020,2021,Wake Forest University Health Sciences,316108,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2016 +C06793,3UH3OD023289-05S1,"Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment","PROJECT SUMMARY/Abstract: The overarching goal of this ECHO COVID-19 Administrative Supplement (NOT-OD-20-107) is to examinechanges in children's obesity-related behaviors that are occurring in tandem with societal changes related tothe COVID-19 pandemic. Prolonged home stays, physical distancing precautions, school closures andeconomic disruption may impact children's dietary intake, physical activity, screen time and sleep. This is acritical gap to fill because obesity prevention and treatment interventions over the next several years will needto be tailored to address the COVID-19-specific causes of obesity. Societal changes may differentially impactchildren from different socioeconomic and racial/ethnic groups and, in turn, exacerbate existing disparities inobesity. Further, variation in the degree of protective measures varies by US state, which may contribute togeographic variation in the effects of the pandemic on child health. Natural experiments are needed to assessthe effects of the pandemic on obesity-related behaviors in a socioeconomically, ethnically and geographicallydiverse sample of children using rigorous measures of diet, activity, screen time and sleep. KaiserPermanente Northern California (KPNC) is 1 of 4 awardees in the ECHO consortium proposing to collaborateon this Administrative Supplement. We propose a quasi-experimental pretest-posttest design among mother-child dyads from the 4 ECHO sites cohorts (n=375 dyads), including KPNC which consists of two pre-birthcohorts currently following offspring in early childhood. For the pretest, we will leverage existing data on diet,activity, screen time and sleep collected from dyads who completed their ECHO visit before March 2020. Forthe posttest, we will collect novel repeated measures data in Fall 2020 and Spring 2021 from the same dyadsusing remote data collection. We will address the following specific aims: AIM 1: to compare diet, activity,screen time and sleep prior to versus during the pandemic, with a focus on identifying children at high risk foradverse changes. We will explore whether the changes in obesity-related behaviors are modified bysocioeconomic status, race/ethnicity and site location: AIM 2: using a mixed method approach (qualitative andquantitative), examine families' daily routines during the pandemic, and parent perceptions of how societalchanges influence children's obesity-related behaviors. The ECHO COVID-questionnaire will quantitativelyexamine parent perceptions of how societal changes influence obesity-related behaviors. Qualitative interviewswith parents will identify COVID-specific barriers to achieving healthy behaviors, reduced access to physicalspaces that promote active play, and parents' reliance on screen time as a replacement for in-person daycare.This study will be significant for ECHO and the broader child health community because lifestyle behaviorchanges during the pandemic may alter obesity risk and amplify existing obesity disparities. Findings from thisstudy will inform programs, policy and practice to prevent childhood obesity during the pandemic and beyond.",2020,2023,Kaiser Foundation Research Institute,310572,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2016 +C06794,3R01AG058539-03S1,ADVANCE: Assessment of Disparities and Variation for Alzheimer's disease in Nursing home Care at End of Life,"COVID-19 is a crisis in U.S. nursing homes (NHs), where residents with advanced dementia are at especiallyhigh risk of acquiring and dying of the virus. There is an urgent need to understand how to compassionately andeffectively care for these residents, maintain communication with family members, and protect the safety of allresidents and staff. Prior quantitative research highlighted persistent regional and racial variation in the intensityof care provided to NH residents with advanced dementia, and the pandemic is revealing profound racialdisparities in the general population. Little is known about the intersection of COVID-19, advanced dementia,and disparities. ADVANCE (Assessment of Disparities and Variation for Alzheimer's disease Nursing home Careat End of life), is an ongoing qualitative study that seeks to understand the drivers of regional and racial disparitiesin care provided to NH residents with advanced dementia. We have identified two high intensity and two lowintensity health referral regions (HRRs) (Rochester, NY, Boston, MA, Birmingham, AL, and Atlanta, GA) basedon tube-feeding and hospital transfers rates ascertained from recent Minimum DataSet data. Within each HRR,two high and low intensity NHs relative to all NHs in that HRR (16 NHs total) were identified. To date, we haverecruited, conducted site visits, and collected extensive qualitative data in 11 of these NHs in 3 HRRs. We haveacquired a rich dataset and conducted extensive analysis to examine how NH organizational culture and staffand proxies' perceptions influence the care residents with advanced dementia receive. The objective of thisadministrative supplement is to leverage the ADVANCE study infrastructure, with its established relationship toa diverse cohort of NHs and proxies, to explore the experience of residents with advanced dementia duringCOVID-19 from the lens of health care disparities. Qualitative data will be collected by interview with NH staffand proxy decision makers for NH residents with advanced dementia. Aim 1, will use remote, semi-structuredqualitative interviews with NH staff (medical providers, senior administrators, nurses, nursing assistants, andsocial workers) in the 11 ADVANCE NHs to explore their experiences caring for residents with advanceddementia during COVID-19 focusing on: care processes (testing, controlling transmission, managing COVID-19positive residents; connecting residents and families); decision-making processes (advance care planning,hospital transfer, communication with proxies); organizational resources (staffing and personal protectiveequipment); and personal experience (health, safety, and stress). Aim 2, will use remote, semi-structuredinterviews with proxies of advanced dementia resident (11 Black and 11 White) about their experience duringCOVID-19 focusing on: connecting with resident, NH response to the crisis, communicating with NH, decisionmaking (advance care planning, hospital transfer), and personal impact (health, coping and stress). IMPACT:The findings of this supplemental research will generate information needed to guide and inform the delivery ofequitable and culturally sensitive care to NH residents with advanced dementia during this crisis and beyond.",2020,2021,Hebrew Rehabilitation Center For Aged,285025,Human Populations,Black | White,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2018 +C06795,3K08HL136857-03S1,"Developing a Low-Cost Intelligent Ventilator with Remote Control for Rapid, Global Deployment and Minimal Healthcare Provider Exposure","PROJECT SUMMARY/ABSTRACTDr. Jason Rose is submitting this administrative supplement in regards to the Notice of Special Interest:Availability of Administrative Supplements on Coronavirus Disease 2019 (COVID-19) under the PA-18-591opportunity. The parent grant is Dr Rose's K08 HL136857 Mentored Research Career Development Award. Dr.Rose is an Assistant Professor of Medicine and Bioengineering at the University of Pittsburgh. His parent grantfocuses on the cardiovascular and mitochondrial effects of carbon monoxide (CO) poisoning and preclinicaldevelopment of an antidote for CO poisoning. As a pulmonary and critical care physician, Dr Rose has beencaring for patients with COVID-19 in the ICU. He helped lead preparations at the University of Pittsburgh MedicalCenter system to secure a healthy personal protective equipment and biotronic (e.g. ventilators) supply chain.The COVID-19 pandemic has progressed around the globe with over one million cases in the United States byMay 2020. Up to 11.5% of US cases require intensive care unit (ICU) admission. In a scenario where a significantportion of the population (5%) develops COVID-19 in a short time period - through a ""second-wave"" of infectionor viral mutation increasing severity or infectivity - up to 1,000,000 could require mechanical ventilation in somemodels. US hospitals only owned 62,000 full-featured ventilators before COVID-19. Initiatives by the US federalgovernment to invoke the Defense Production Act (DPA) will produce 130,000 new ventilators costing over $2.5billion dollars. Further, while the DPA has activated the final assembly of ventilators, there is likely to be ashortage of key components (e.g. advanced semiconductors). Conversely, available low-cost and easy-to-fabricate emergency ventilators have limited function and cannot reliably ventilate COVID-19 patients with acuterespiratory distress syndrome. These simple devices tax the limited critical care workforce with more bedsidepatient monitoring and additional training. Limiting unnecessary exposures to patients will protect workers.The central objective of this proposal is to develop a rapidly manufactured, full-capability adult ICU ventilator(""Robotic Ventilator"" - RoboVent) that can be controlled remotely to meet worst-case global ventilator demandat reasonable cost (<$800/unit). Aim 1: The device will be prototyped, using robotic principals, using easy-to-fabricate components. The RoboVent will provide closed-loop pressure assist-control (AC), volume AC andpressure-support modes of ventilation. Using novel sensing, control and actuation technology, developed by ourgroup, the ventilator will offer full control over driving pressure (or tidal volume), positive end-expiratory pressure,respiratory rate, and inspiratory to expiratory ratio. Aim 2: The device will be validated for internal consistencyand tested against commercially available adult ICU ventilator units using a test lung simulators. A pilotproduction batch will be validated similarly. These data will be submitted for FDA emergency use authorization.Following this work, the technology will be licensed to a new startup entity and up to 10,000 FDA-cleared remoteventilators per week can be deployed in conjunction with manufacturing partner Foxconn Technology Group.",2020,2023,University Of Pittsburgh At Pittsburgh,160708,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2018 +C06796,3R01DC016272-01A1S1,Determining Optimal Treatment Intensity for Children with Language Impairment (LI),"Project Summary/Abstract This urgent revision will determine the optimal treatment intensity for children with language impairment (LI), provided via telepractice platforms, by systematically manipulating treatment dose and frequency. This study will also investigate the moderating influence of the home environment on children's outcomes. This study aim is urgent in that over 1 million children with LI are no longer receiving language services in the public schools, as prescribed by their IEPs, due to COVID-19. Children instead are either receiving supplemental resource packets or receiving therapy via telepractice - a grossly understudied platform for service provision for this population. Preliminary studies of children with LI in the public schools suggest that children with LI who received high frequency/low dose treatment (or low frequency/high dose) made better gains over time than children receiving the extremes (overall low or high intensity of treatment; Schmitt et al., 2017). These preliminary findings are correlational in nature; the current study aims to manipulate both parameters of intensity (dose and frequency) to determine not only the interactive influence of dose and frequency on children's gains, but also the extent to which factors of the home environment - now a primary learning environment for school age children - influence the dose and frequency required to realize language gains. To address these aims, the proposed study will utilize the methods proposed in the parent study of optimal treatment intensity now on a telepractice platform. Participants (60 children with LI recruited from two US states) will be randomized into one of two frequency conditions (massed vs spaced) in which they will receive a word learning intervention previously tested through NIH funding by Holly Storkel and colleagues (e.g., Storkel et al., 2017). The intervention identifies 60 new vocabulary targets which are presented to children within story book readings using rich vocabulary intervention strategies. For the purposes of the proposed study, each vocabulary target (n = 60) will be randomized to one of six possible dose exposures (0, 4, 8, 12, 16, 20) for each child. SLP interns will deliver the manualized word learning intervention in one-on-one sessions for 10 weeks via telepractice platforms. Comprehensive measures of the child's home environment will be collected before treatment, all via questionnaires and online interviews. Children's vocabulary skills will be measured via telepractice at three time points: pre-treatment, immediate post-treatment, and 6-months post treatment to assess the impact of the intensity regimens on outcomes. Analyses will specify a dose-response curve to identify the point of optimal gain children receive from treatment as well as moderating influences of the home environment. Findings will immediately inform practice for school-based SLPs during the COVID-19 crisis as well as provide intensity parameters and familial considerations for future clinical trials.",2020,2024,"University Of Texas, Austin",195346,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Other secondary impacts | Health service delivery,2020 +C06797,3UH3OD023305-05S1,"NYU Pediatric Obesity, Metabolism and Kidney Cohort Center","PROJECT Summary: The novel coronavirus pandemic (COVID-19) has largely spared children, with relatively few requiring medicalcare. A small case series failed to reveal effects on birth outcomes in mothers with COVID-19 pneumonia, yetthe absence of effects may in part relate to these mothers having been infected in third trimester, as the timingof infection is well known to influence adverse effects in pregnancy. A major barrier to population-basedstudies of SARS-CoV-2 infection has been the lack of a noninvasive method to detect viral RNA.Nasopharyngeal swabs are invasive, require personal protective equipment and swabs which have been inlimited supply, and may be less sensitive than salivary samples for SARS-CoV-2 detection. Studies ofadaptive immunity following infection in children have also been limited by the need for venipuncture to collectsufficient serum for validated testing of antibody. Our research team has developed novel methods formeasuring SARS-CoV-2 infection in saliva, as well as IgG and IgM antibody responses to the spike protein andthe receptor binding domain of SARS-CoV-2 in dried blood spots (DBS). Substantial psychosocial stress islikely to have occurred in pregnant women during the pandemic, whether due to fear of infection, job loss,economic stress, psychological or physical trauma, or other factors. Psychological stress during pregnancy isknown to increase prematurity, yet stress and viral effects have not been examined together as yet. We hadpreviously received PO permission to reallocate Year 4 funds in the NYU Children's Health and EnvironmentStudy (CHES, UH3OD23305) and the Columbia Center for Children's Environmental Health (CCCEH,UH3OD023290) to add remote and repeated saliva, dried blood spot, and hair collection in cohortsprospectively enrolling mothers into ECHO, using kits assembled by Fisher BioSciences for the ECHOprogram. We propose to expand this effort over the next year to newly enrolled mothers in NYU CHES (N=200mothers), CCCEH (N=20 mothers) as well as the Michigan Archive for Research in Children's Health (MARCH,UH3OD23285, N=20 mothers). We also wish to continue data collection in already enrolled NYU CHES(N=340 pregnant women as of March 1, 2020) and CCCEH (N=40 pregnant women as of March 1, 2020)mothers. The data will be supplemented by chart Abstract: Ion for all SARS-CoV-2 testing.",2020,2023,New York University School Of Medicine,339000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences,2016 +C06798,3P20GM104420-06A1S1,Center for Modeling Complex Interactions,"Modeling efforts for COVID-19 within the US have focused primarily on helping urban centers cope with theconsequent health care crisis. The impact of the pandemic on rural communities is still emerging, and theseareas have not received the same degree of modeling attention. At the same time, rural communities aredifferent from urban centers in ways that affect the disease and its dynamics: they have lower densities, aremore isolated, have smaller social networks, tend to be poorer and older, and have scant health careinfrastructure. Rural communities are also the primary source of food production and natural resourceextraction in this country. As the pandemic unfolds across the coming months, rural communities will be facedwith highly variable circumstances: some will have no infections and be focused on early detection; some willhave active cases and be attempting to stop their spread; some will have eliminated active cases and beattempting to reopen economic and community activities while guarding against resurgence. Treating allcommunities as the same would be foolish. At the local level, decision makers need tools tailored to realcommunities: tools that emulate the way people come and go and interact there, tools to consider the mostrelevant interventions, and tools that account for real variation in how able and willing people will be to complywith possible interventions. At the larger health-district and state level, officials need forecasts of how localdecisions, health care infrastructure, and the virus itself will interact to drive the epidemic. The purpose of thecurrent proposal is to provide these tools by building a model of COVID-19 for largely rural states that links thedynamics within communities together into a statewide network. This will be achieved in three specific aims. InAim 1, we develop a predictive epidemiological model of COVID-19 spread and intensity for rural states. Thiswill be done with a spatial, age-structured metapopulation model that relies on differential equations and theirstochastic extensions. In Aim 2, we evaluate how potential interventions in individual communities affectoutbreak risk, transmission, access to health care, and intervention efficacy and adoption. Here we combinesurveys-of both rural and urban communities in Idaho and several broader regions of the US-to estimatepatterns of compliance and the motivations behind them. Using these results, we will then use agent-basedmodels of synthetic communities to simulate interventions. Net effects will be relayed up to the statewidemodel. In Aim 3, we provide support for decision making to state public health officials and local policy makersin rural communities. This will be done by developing two online graphical interfaces for visualizing forecastsand exploring interventions-one high-level application for non-specialists and a second, more sophisticatedversion, for public health professionals. Education, empowerment, and appreciation of uncertainty will beemphasized. Finally, the models and tools we develop here will be implemented in Idaho, but will be designedfor easy export to states with significant rural populations.",2020,2025,University Of Idaho,492598,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions,2015 +C06799,3U01CA202979-05S1,COVID-19 Pandemic and Its Effects Within the Southern Community Cohort Study,"This supplemental application (PA-18-591) is submitted in response to NOT -OD-20-097 to enhance theSouthern Community Cohort Study (SCCS) data to permit evaluation of the effects of the CoronavirusDisease 2019 (COVID-19) pandemic within the SCCS, a prospective cohort study that includes primarilyAfrican American and low-income populations in the southeast US. COVI D-19 has resulted in a globalpandemic. The burden of these outbreaks appears to be unequally shared in the US, with reports that rates ofinfection or severe outcomes, including death, are more common among older adults, those with comorbidities,and African Americans. Transmission reduction is only achievable through adherence to individual infectionprevention behaviors and community-level interventions, such as social distancing. As the COVID-19pandemic is expected to last multiple months and perhaps years, there is an urgent and unmet need tounderstand 1) the extent of adherence to infection prevention recommendations, particularly among individualsat high risk for adverse outcomes, and 2) the factors that are associated with adherence in order to informcontinued interventions for infection prevention. In addition, the same public health measures intended toreduce transmission have also resulted in record levels of unemployment, social isolation, food insecurity, andmany other challenges. While these effects have been observed across multiple US populations, they alsohave the potential to exacerbate existing health disparities in vulnerable populations or to create new ones.The effect of the pandemic on lifestyle factors related to cancer or other chronic diseases and the general wellbeingof already vulnerable populations is not yet well described nor understood. Many pandemic interventionshave been aimed at 'flattening the curve' in order to reduce the potential to overburden the health care system,including the cancellation or delay of health care procedures and appointments. There are many additionalpotential factors which could affect access to and utilization of health care services during the COVID-19pandemic, all of which may result from or exacerbate cancer and other health disparities within the US. Thus,the aims of this supplemental application are 1) To determine adherence to SARS-CoV-2 infection preventionand transmission reduction recommendations and individual and contextual factors that are associated withadherence; 2) To evaluate racial/ethnic, socioeconomic, geographic and urban/rural disparities in well-beingand lifestyle behaviors resulting from the COVID-19 pandemic containment and mitigation efforts; and 3) Toevaluate racial/ethnic, socioeconomic, geographic and urban/rural disparities in healthcare access during theCOVID-19 pandemic, including access to SARS-CoV-2 testing, as well as routine and urgent clinical care. Thedata from this study will enable better quantification of COVI D-19 pandemic effects in a diverse US populationclassified by race, geography, socioeconomic status, and other attributes. These findings will help to informindividual-level and community-level public health interventions during the COVID-19 pandemic.",2020,2021,Vanderbilt University Medical Center,172983,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Social impacts | Health service delivery,2016 +C06800,3R01DK119667-02S1,Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and Survival,"Abstract.COVID-19 was declared a pandemic by the World Health Organization. COVID19 is caused by severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the coronaviridae, a diverse family ofviruses that cause a range of diseases in humans and animals. Recent clinical studies show a strong associationwith COVID-19 and diabetes. Additional studies suggest that diabetes is not only a risk factor for severe COVID-19 disease but also that SARS-CoV-2 infection can induce a new onset diabetes. However, it is not clear whatdiabetes-associated cells are infected by the virus and how these cells respond to SARS-CoV-2 infection.A number of studies support the hypothesis that viral infections play a causative role in Type 1 diabetes (T1D).Enterovirus isolates obtained from newly diagnosed T1D patients can infect and destroy human islet cells in vitro.In T1D patients, beta cell mass decreases due to auto-immune destruction. Here, we assemble a multi-disciplinary investigator team, including expert beta cell biologist (Dr. Chen), stem cell biologists (Drs. Evans andSchwartz), and a virologist (Dr. tenOever) to systematically study the impact of SARS-CoV-2 on pancreaticendocrine cells and test the hypothesis that SARS-CoV-2 infection causes human pancreatic endocrine celldestruction. In preliminary studies, we found that human pluripotent stem cell (hPSC)-derived pancreaticendocrine cells are permissive to SARS-CoV-2 infection, which was further validated using adult primary humanislets. Transcript profiling following SARS-CoV-2 infection of hPSC-derived pancreatic endocrine cells revealedstriking upregulation of chemokines, similar to profiles of tissues obtained after autopsy of COVID-19 patients.In addition, we performed two high content chemical screens and identified several FDA-approved drugs thatshow anti-SARS-CoV-2 activities on both hPSC-derived colonic and lung organoids. Here, we propose tovalidate the SARS-CoV-2 infection using pancreatic samples from COVID-19 patients, examine the impact ofSARS-CoV-2 infection on human endocrine cells, and re-purpose FDA-approved drugs to protect humanpancreatic endocrine cells from SRAS-CoV-2 infection. Three aims are proposed:Aim 1. Validate SARS-CoV-2 infection in pancreatic samples from post-mortem COVID-19 patients.Aim 2. Examine the impact of SARS-CoV-2 infection on human pancreatic endocrine cell function and survival.Aim 3. Repurpose FDA-approved drugs to protect human pancreatic endocrine cells from SARS-CoV-2 infection.Through this study, we expect to provide direct pathogenic evidence of SARS-CoV-2 infection of humanpancreatic endocrine cells, understand the pathogenesis of SARS-CoV-2 infected pancreatic endocrine cells,and develop novel approaches to protect human endocrine cells from SARS-CoV-2 infection.",2020,2023,Weill Cornell Medicine - Cornell University,397733,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2019 +C06801,3P30CA069533-22S3,"Understanding the impact on COVID-19 on health behaviors pertaining to cancer prevention, screening, and treatment activities and the mental health and well-being of cancer survivors","Project Summary/Abstract: The COVID-19 pandemic in the US and the world has had an impact both physical to psychological onindividuals far beyond that of the acute illness. While resources and attention have rapidly and appropriatelyshifted to this current crisis, it is unclear how the virus and necessary community level responses to slow thespread of the virus have impacted ongoing needs for cancer prevention and screening activities as well astreatment and support for the particularly vulnerable cancer survivor population. Impacts of the pandemic mayvary from simply delaying screening activities, to changed perceptions regarding cancer risk, to feelings ofbeing disconnected from needed services, to disruption of treatment and suspension of social supports forcancer survivors. Our proposed research explores and quantifies the impact of COVID-19 and the necessarypublic health response to the crisis on cancer screening and risk behaviors among a random sample ofindividuals across our catchment area, as well as the unique and potentially more challenging effects oncancer survivors. An early understanding of these issues will allow us to be more effective in providingnecessary novel supports to cancer survivors as well as identifying how to maintain screening and riskreducing behaviors both during the crisis and as we slowly return to a more normal state.Surveys, using constructs agreed upon by funded collaborating cancer centers and the NCI, assesspsychosocial and behavioral impacts of COVID-19 on two target populations, a stratified probabilistic sample ofhouseholds in Oregon and cancer patients and survivors from the Knight Cancer Institute residing in Oregon.Using an entirely app based data collection platform, the Healthy Oregon Project (HOP), surveys will beadministered in a manner that allows for ease of participation from any location with cellular service, does notrequire in person contact, and is highly flexible allowing for the addition of surveys and opportunities foradditional study contact rapidly and inexpensively. Differences in knowledge and attitudes about COVID-19,mitigation interventions related to the global pandemic, and its impact on mental health and well-being will areassessed through the application of multiple statistical approaches. Results from this research will inform acancer center's understanding of the impacts of COVID-19 on cancer prevention and control and help guidedevelopment of education and communication strategies designed to effectively address specific challengesthat were brought about by both the disease and our necessary social and public health response to thedisease.",2020,2022,Oregon Health & Science University,154000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,1997 +C06802,3UH3OD023279-06S2,Environmental Influences on Child Health Outcomes in the Northern Plains Safe Passage Study Cohort,"Project Abstract COVID-19 will leave an indelible mark on this period in history. The proposed project is designed todevelop and test strategies and best practices that will optimize remote data and specimen collection duringthe COVID -19 crisis. Using a mixed methods approach will gather information on the feasibility andcompleteness of data collected remotely during this period. We will identify whether racial, geographic andsocio-economic disparities influence the process and quality of remote data collection. This proposal includescollaborative studies led by the University of Colorado (Dabelea) and the University of New Mexico (Lewis). Incollaboration with investigators from Colorado, California, and New Hampshire, we are participating in a time-sensitive, ECHO-wide study to examine changes in obesity-related behaviors that are occurring in tandem withsocietal changes related to COVID-19.",2020,2023,Avera Mckennan,290000,Human Populations,Other,Children (1 year to 12 years) | Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2016 +C06803,3UH3OD023290-05S1,CCCEH ECHO COVID19 Supplement,"PROJECT SUMMARY/ABSTRACTWithin the ECHO consortium, Columbia Center for Children's Environmental Health (CCCEH) has threelongitudinal pregnancy cohorts comprised primarily of African American and Hispanic mothers and theirchildren, who were recruited during pregnancy beginning in 1998. The three cohorts span all ECHO life stagesand represent an urban, minority population that is typically under-represented in scientific research. The 2019novel coronavirus (COVID-19) pandemic has had worldwide impact; during the ""first wave"", New York City(NYC) was identified as the U.S. epicenter. There are many early indicators suggesting that urban minoritycommunities were among the most affected by the COVID-19 pandemic; and effects of exposure to thepandemic vary by life stage. To develop strategies to mitigate these disparities and to more fully understandthe impact of COVID-19 on the health and welfare of children living in the most affected communities duringthis pandemic, our group is contributing to 3 ECHO supplement concepts. Collectively, these conceptsaddress the impact of the COVID-19 pandemic on nearly every outcome domain within ECHO: perinatal;respiratory; neurodevelopmental; and positive health outcomes. Specifically, the aims address the impact ofinfection; the broader impact of the pandemic and its associated policies (e.g., lockdowns) on environmentaldeterminants of health; and the impact on social determinants of health. In complete alignment with the ECHOmission, this proposal addresses the impact of exposure to the COVID-19 virus and concurrent pandemic-related changes in the environmental chemical and psychosocial environments on child health, development,and well-being overall and within urban, minority communities. Given the long-lasting impact of the COVID-19pandemic, it is critical to understand how these factors influence child outcomes measured in ECHO,particularly among a subgroup of the study population that may be among the most highly impacted.Collectively, our proposal seeks to learn from the pandemic, using it as an opportunity to inform the futuredevelopment of more effective programs and policies that protect and support all children, especially the mostvulnerable.",2020,2023,Columbia University Health Sciences,323665,Human Populations,Black | Other,Adults (18 and older) | Children (1 year to 12 years),Urban Population/Setting,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Other secondary impacts,2016 +C06804,1R21ES032762-01,The External Exposome and COVID-19 Severity,"PROJECT Summary: The 2019 novel coronavirus disease (COVID-19) is a global pandemic with severe medical and socioeconomicconsequences. Young adults without any underlying health conditions can still develop severe COVID-19disease, and there are racial and ethnic disparities in COVID-19 hospitalization and mortality rates whichcannot be explained by age and underlying health conditions alone. Risk factors of severe COVID-19 beyondolder age and underlying health conditions are large unknown. There are large overlaps between the currentlyknown risk factors of severe COVID-19 and the health conditions that are affected by environmentalexposures, and emerging evidence suggested that long-term environmental exposures may be importantdeterminants of COVID-19 severity. Traditional environmental epidemiological studies usually examineenvironmental factors separately without considering ""the totality of the external environment"". Such studiesare not only time consuming as they examine individual exposures separately, but more importantly, cannotaccount for confounding by co-exposures. The external exposome is an ideal framework to identify novelexposures associated with severe COVID-19 as it can systematically and efficiently screen thousands ofenvironmental exposures. In this project, we will leverage a unique real-world data (RWD) resource -OneFlorida - a large repository of linked electronic health records (EHR), claims and vital statistics data,covering more than 60% of Floridians, contributing to the national Patient-Centered Clinical Research Network(PCORnet). Building on our prior work on the external exposome, we will expand our existing externalexposome database to include additional factors that may impact COVID-19 outcomes through a systematicanalysis of literature and resources. We aim to (1) develop phenotyping algorithms for identifying a COVID-19cohort and their severity and extracting associated individual-level risk factors from the OneFlorida real-worlddata, and (2) identify external exposome factors associated with severe COVID-19, examine how the externalexposome contributes to racial and ethnic disparities in severe COVID-19, and build predictive models ofsevere COVID-19 with external exposome factors. This study will fill important knowledge gaps by providingtimely information to understand how environmental exposures may impact COVID-19 severity that willimprove identifications of high-risk COVID-19 patients and inform the design of future precision interventions.Our approach and initial results for Florida can (1) be readily scaled up to a multi-state study through PCORnetand (2) answer other novel questions such as the external exposome's contribution to geographic disparities inCOVID-19 outcomes.",2020,2022,University Of Florida,221908,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06805,3U01DK062413-19S1,Genetic and genomic approaches to better understand the clinical heterogeneity in inflammatory bowel diseases,"The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), aresignificant causes of morbidity with recent estimates suggesting there are more than 3 millionAmericans with IBD with very significant financial burden to the US economy. The world iscurrently in the middle of a global pandemic caused by SARS-CoV2 which is the cause of COVID-19. Preliminary studies have identified shared molecular signatures between IBD and COVID-19.Of interest is that the receptor for SARS-COV2 is angiotensin converting enzyme 2 (ACE2) whichis most highly expressed in the gut. Our preliminary data suggests that expression of this receptoris influenced by age and obesity as well as in IBD. Differing patterns suggest differences bydisease location. Interestingly our preliminary data suggest that anti-cytokine therapy alters ACE2expression in inflamed tissue. We propose to study the overlap between these 2 conditions usinga large-scale and comprehensive genetic approach. We will study genetic variants in ACE2 andrelated genes for their effect on IBD susceptibility and disease progression as well as responseto therapy. We will study, in depth, large numbers of gene expression samples from IBD cases toinvestigate this overlap further. We will use a newer technology called single cell RNAseq todetermine which cells are leading to the changes in gene expression that we have seen with ourinitial studies. We will also use a statistical approach called Mendelian Randomization (which canbe viewed as nature's equivalent of a randomized study) to determine whether the therapies usedin IBD are likely to be beneficial or harmful in COVID-19 infection. We will use these data toidentify subjects in whom to generate pluripotent stem cells for functional work. For the functionalstudies we will use gut organoids and the IPSCs to test the effect of cytokines that reflect thedifferent inflammatory states that we have observed (ageing, obesity, ileal inflammation, colonicinflammation) on ACE2 expression. The results from these analyses will also help us refine our'big data' approach described earlier. We anticipate that these studies will give us insights intothe molecular overlap of IBD and COVID-19 and what are the likely effects of anti-cytokine andother treatments used in IBD likely to be in COVID-19.",2020,2022,Cedars-Sinai Medical Center,346893,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2002 +C06806,3P20CA233307-02S1,UChicago Interdisciplinary Cancer Health Disparities SPORE,"This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOTCA-20-042. The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is a public health and economic emergency that has disrupted the lives of breast cancer patients. Unfortunately, it has hit the United States heavily with more than 1.7 million people having been infected and more than 100,000 lives lost to date. While old age and having comorbidities are risk factors for dying from COVID-19, there is also a racial disparity in COVID-19 severity, with black and Latino patients in urban centers dying disproportionately from COVID-19. Breast cancer is the most common malignancy in women, with over 3.8 million women living in the United States with a history of invasive breast cancer. African Americans with breast cancer have an elevated risk of all-cause mortality and breast cancer-specific mortality. During the COVID-19 pandemic, it is important to understand the impact of SARS-CoV-2 infection and COVID-19 on breast cancer disease progression, care delivery, and survivorship including quality of life during and after the COVID-19 outbreak. In response to the needs of patients participating in our P20 funded UChicago Interdisciplinary Health Disparities SPORE and to address these knowledge gaps, we propose to engage with the Community by conducting an online survey, reviewing electronic health records, and searching the National Death Index to determine status of 3,059 breast cancer patients in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. The project has three specific aims: First, we will evaluate the extent of treatment interruption because of COVID-19 outbreak, and understand the utilization and satisfaction with Telehealth. Second, we will conduct a holistic evaluation of COVID-19 and mitigation efforts on loneliness, anxiety, stress, economic impact, and lack of resources among breast cancer patients. Third, we will estimate the coronavirus infection rate, severity and case-fatality rate of COVID-19, and identify factors associated with severity and case-fatality rate of COVID-19. For each aim, we will examine racial differences to understand whether COVID-19 has worsened previously identified mortality gap in the Cohort. The Supplementary Project will greatly enhance our SPORE P20 program by supporting additional interviews and follow-up of the cancer cohort members, and will generate necessary data regarding the impact of COVID-19 epidemic and lockdown on translational research to close the mortality gap in our proposed full SPORE application. These data are critical for guiding both community level interventions and health systems adaptation to support high-risk patients in the era of COVID-19.",2020,2021,University Of Chicago,162000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts | Economic impacts,2020 +C06807,1R21AI158229-01,"Immunomodulatory effects of coronavirus membrane proteins E, M, and S.","Abstract: COronaVIrus Disease 2019 (COVID-19) is caused by a human coronavirus, SARS-CoV-2. This viruscaused a large outbreak in China that was associated with a high human-to-human transmission rate and mortalityand subsequently led to a pandemic in the human population. SARS-CoV-2 is member of the â-coronaviruses andis highly related to SARS-CoV. In an ongoing evolutionary arms race, viruses have evolved factors that facilitatetheir replication while the host cell has evolved signaling networks to detect and eradicate invading viruses. Theinnate immune system is a conserved defense strategy critical for the initial detection and restriction of pathogensand later activation of the adaptive immune response. Activation of innate immunity relies on the recognition ofpathogen-associated molecular patterns (PAMP) by pattern recognition receptors (PRRs) such as Toll-likereceptors, RNA and DNA sensors. Upon activation by PAMPs, PRRs recruit adaptor proteins that initiate signalingpathways involving modifying enzymes such as kinases, phosphatases, E3 ubiquitin ligases that ultimately leadto the activation of crucial transcription factors including IRF3 and NF-êB. Synergistically, these factors promotethe production of antiviral type I interferons (IFN-I), inflammatory cytokines, NK cell immunity, apoptosis, andautophagy. Thus, the pathogenicity and spread of a virus in the host is in part determined by the ability of the virusto evade host cell innate responses. The SARS-CoV-2 virion has three transmembrane proteins [envelope (E),membrane (M), and spike (S)] that are necessary for viral assembly and infectivity. They also have importantimmunomodulatory functions as they trigger or antagonize innate immune responses within infected cells. TheE proteins from other coronaviruses have been shown to form an oligomeric structure with ion channel activity thatcan alter calcium homeostasis with implications on viral pathogenesis. The M protein of other coronaviruses wasshown to have a range of immunomodulatory effects through TLR-dependent and independent mechanisms andthe S protein can exert its effects by modulating surface signaling responses. It also causes the degradation ofBST-2 (tetherin), which functions to prevent release of progeny virus. We hypothesize that theimmunomodulatory properties of SARS-CoV-2 membrane proteins will determine the outcome of theinfection and viral mediated pathogenesis. To test this, in Aim 1, we propose to examine E, M, and S proteinsfrom SARS-CoV-2 and compare their impact in modulating innate immunity, proinflammatory responses,autophagy, and apoptosis with the same proteins from SARS-CoV, MERS-CoV, and HCoV-OC43. In Aim 2, wewill determine the immunomodulatory effects of virus-like particles (VLPs) formed by the membrane proteins ofthe four viruses. We will also determine the immunoevasion capabilities of of SARS-CoV-2 and compare themwith SARS-CoV, MERS and HCoV-OC43. Overall, the results of these studies will further our knowledge ofimmunoevasion strategies of human coronaviruses and guide in the development of efficacious vaccines.",2020,2022,University Of Kansas Medical Center,420750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C06808,3UL1TR002243-04S3,"Passive Immunity Trial for Our Neighbors (PassITON): A randomized, placebo-controlled multi-site trial of anti-SARS-CoV-2 convalescent plasma to treat hospitalized adults with COVID-19","The Vanderbilt Institute for Clinical and Translational Research (VICTR) is a highly functionaland integrated clinical and translational (C&T) research infrastructure that has raised the qualityand scientific rigor of the research conducted at Vanderbilt and longstanding partner Meharry,the nation's oldest historically black academic health science institution. VICTR will contribute tothe mission of the CTSA program while leveraging unique resources and expertise withinVICTR's Hub with these aims: 1) Leverage VICTR's strong collaborative energy to enhanceteam science methodologies that propel transdisciplinary research approaches, and integrateproven community engagement principles to stakeholders for all stages of research; 2) Develop,implement and disseminate informatics and data organization methods to promulgate researchefficiency, quality, and preparedness and integrate data collection in the conduct of pragmatictrials; 3) Ensure the translational science workforce is diverse and has the skills, knowledge,and resources necessary to advance translation of discoveries; 4) Measurably improve theefficiency, quality, and representativeness of C&T studies by enhancing and systematicallyintegrating services and programs that support highest quality research initiation and conduct;5) Measurably improve the efficiency and quality of multi-site clinical trials, in collaboration withthe TICs and RICs, by leveraging centralized regulatory and legal agreements, providing rapidfeasibility and recruitment methods and practices, and creating and disseminating novel clinicaltrial designs and methodologies; and 6) Utilize unique strengths leveraging novel resourcesBioVU and PheWAS to guide drug development and repurposing.",2020,2022,Vanderbilt University Medical Center,34000000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Unspecified,Data Management and Data Sharing,,,United States of America,,,,2017 +C06809,3R21AG060018-02S1,"Understanding the role of ApoE2 in longevity and age-related diseases and conditions using 500,000 UK Biobank participants","Genetic susceptibility of ApoE to delirium and dementia in COVID-19confirmed casesProject Summary: Delirium is an acute confusional state that is commonly seen in hospitalized older adultsduring periods of infection, water and electrolyte imbalance or recovering from surgery.Delirium is often preventable, yet it appears to be particularly frequent and severe in thecontext of severe COVID-19 infection. Little is currently known of the mechanism linkingCOVID-19 to delirium, which is a risk factor for long-term cognitive impairment anddementia (mostly Alzheimer's disease). We aim to study the genetic susceptibility ofApoE to COVID-19 related delirium and dementia as ApoE e4 allele has beenassociated with delirium and dementia using general population samples. In COVID-19positive cases with no history of cognitive impairment and dementia, we hypothesizethat patients with ApoE e3e4 or e4e4 genotypes are more likely than those with e3e3(wild type) to experience delirium during COVID-19 related hospitalizations, and to bediagnosed with cognitive impairment and dementia in the 6 months following COVID-19diagnosis. We also hypothesize that patients who develop delirium during coronavirushospitalization are at higher risk of cognitive impairment and dementia in the 6-monthfollow-up. Additionally, COVID-19 is caused by the novel coronavirus SARS-Cov-2 thatenters cells by targeting ACE2 receptors. We therefore also hypothesize that theassociations between ApoE genotypes and delirium or dementia are moderated bygenetic variants in the ACE2 gene. We propose to test the hypotheses using the UKBiobank data, including existing genetic and phenotypic data, now linked to COVID-19testing results and related hospital admission and primary care data: 669 positive casesof 1,474 tested participants in the first month, with numbers growing substantially overtime. The findings of this project will shed light on the biological mechanisms of deliriumand dementia related to COVID-19, and have important implications for themanagement of public health and clinical interventions. This supplement grant isproposed under a NIA-funded R21 (R21AG060018) to study the role of ApoE e2 allelein aging via a wide range of aging phenotypes. The applicant group have extensiveexperience undertaking aging oriented analyses in UK Biobank, including papers ondelirium and ApoE. Additionally, Pilling (Co-I) has a grant funded by the NIA-fundedNIDUS Network (R24AG054259), to study genetic variation and predisposition todelirium.",2020,2021,University Of Connecticut Sch Of Med/Dnt,69066,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2018 +C06810,3R01DC005575-19S1,Genetic underpinnings of dysosmia in COVID-19,"Abstract entitled ""Genetic underpinnings of dysosmia in COVID-19"": There is evidence that smell and tastedysfunction is an early and often the only identifier in COVI-19 positive patients. We hypothesize that geneticvariants in specific candidate genes associated with the development of unique sensory phenotypes of COVID-19patients: In patients reported to the American Academy of Otolaryngology-Head and Neck Surgery using the COVID-19Anosmia Reporting Tool for Clinicians, in the first 237 entries anosmia was noted in 73% of patients prior to COVID-19diagnosis and was the initial symptom in 26.6%. The occurrence in asymptomatic individuals makes this finding a usefultarget for public health screening and would facilitate earlier diagnosis and treatment, as well as the identification of thoseindividuals who are not ill but still capable of spreading the disease. The mechanism underlying sensory alteration iscurrently unknown. Infectious diseases may demonstrate a heritable component - that is the propensity to contract anddevelop active infection and the severity of the immune response is influenced by host genetic factors to some extent andmay reflect inter-individual variation in the host immune response. The genetic basis of this variability in response willprovide important clues for therapeutics and lead to identification of groups at high risk of death. Public health measuresto identify those at increased genetic risk of severe infection would be useful as a way of mitigating the economic effectsof lockdown and social distancing policies. The genetic influence on COVID-19 symptoms may reflect genotype status ofcandidate genes such as ACE2 and TMPRSS2. Our team has been on the forefront to collect preliminary data on thepresence of neurosensory disturbances in COVID-19 patients. We and others reported that anosmia is an importantpredictive symptom of COVID-19. Moreover, a UK twin study has shown that anosmia in COVID-19 patients has a highheritability (h2 = 0.48), suggesting that an individual's genotype plays a role in the presence or absence of this symptom.The goal of this study is to determine the susceptibility which may be influenced by host genotype to sensory disorders inCOVID-19 patients to estimate the heritability of covid-19 sensory symptoms. In this study we will expand our work onfollowing Specific Aim: Identify genetic variation associated with the development of dysosmia in COVID-19patients. We hypothesize that there are genetic variants in the candidate genes that underlie smell and taste dysfunction inboth symptomatic and otherwise asymptomatic COVID-19 patients. Preliminary data: We have established aninternational interdisciplinary collaboration team and have collected and published preliminary data on the role of ENT inCOVID-19 and on the prevalence of sensory dysfunction in COVID-19 in our pilot studies. To determine if variants inspecific candidate genes are associated with the development of anosmia in COVID-19 patients, we will collect DNAsamples in our local COVID-19 patients and international patients from our collaborators for the study. In our hospitals,we have access to over 462 patients with confirmed positive COVID-19, 1565 with confirmed negative, and 390 patientswith pending testing results. Over 10% of these patients report smell and taste dysfunction; our international collaboratorshave a large cohort of COVID-19 patients with smell and taste dysfunction available to us as well (see their LOS). We willperform WES on 120 samples from COVID-19 patients including 60 with smell and taste dysfunction and 60 without. Wehave established a COVID19 blood sample treatment process at our pathology lab for our ongoing study. Whole exomesequencing will be performed using established methods in the Center for Genome Technology in the Hussman Institutefor Human Genomics (HIHG). Innovations in our proposal include: 1. Identify genetic markers for the early detectionof mild and asymptotic COVID-19. 2. Our minority focused Miami sensory screening and genomic screening pipeline,and a database of genomic variation and phenotypes - sensory disorders and COVID-19-positive people. 3. Amultidisciplinary, international collaboration with samples for duplicating studies.",2020,2022,University Of Miami School Of Medicine,191875,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2001 +C06811,3R01DC012115-08S1,Sensory disorders in COVID -19 as an early identifier and healthcare worker protection,"Abstract: Neurosensory symptoms are a well-known but poorly characterized sequelae of SARS CoV-2infection. In particular, there is evidence that smell and taste disturbances may sometimes be an early orsingular marker of SARS-CoV-2 infection. ENTs and other clinicians involved in the diagnosis and treatmentof sensory and communication disorders are by the nature of their work at high risk for exposure to respiratorypathogens. Furthermore, due to this high risk of disease exposure and infection, they are also particularlyvulnerable to stress and emotional disturbances. Our team has been on the forefront to collect preliminary dataon the presence of neurosensory disturbances in COVID-19 patients, the role of ENT in the treatment of thesepatients, and the protection of the physical and mental health of high risk health care workers. In this study wehope to further expand our work on these topics through the following specific aims: Aim 1 - Investigate theincidence and characteristics of sensory disorders in COVID-19 patients including anosmia, dysgeusia, dizziness, andhearing loss; Aim 2 - Assess the role of ENT in the treatment of COVID-19 and the effectiveness ofimplemented PPE measures; and Aim 3 - Evaluate mental health symptoms in high-risk healthcare workersduring and after the COVID-19 pandemic.We have established an internationally interdisciplinary collaboration to pursue our work on thesetopics including experts from China, Germany, and France. In our hospitals, we have access to our local patientsincluding over 462 patients with positive COVID-19, 1565 with confirmed negative, and 390 patients with pendingtesting results as well as a large cohort of COVID-19 patients from our international collaborators (see their LOS) forthe current study. We have published or are working to publish a variety of preliminary data including thefollowing studies: ""Approaching otolaryngology patients during the COVID-19 pandemic"", ""Olfactory ortaste disorders as an early identifier of COVID-19 in adults and children: an international multicenterstudy"", ""Low Rate of Seroconversion in High Risk Medical Professionals Using a Novel Assay for COVID-19 Exposure"", ""A Systematic Approach to Early Identification and Healthcare Worker Protection"",""Otolaryngology providers must be alert for mild and asymptomatic COVID-19 patients"" and ""COVID-19:Specific challenges faced by Individuals with Autism spectrum disorders and their family"". Innovationsin our proposal include: 1. A multidisciplinary, international collaboration; 3. Our minority focusedMiami sensory screening pipeline, and a database of genomic variation and phenotypes - sensorydisorders and COVID-19-positive people; and 3.Identifying a sensory impairment battery for the earlydetection of mild and asymptotic that can be incorporated into population-based screening studies.",2020,2023,University Of Miami School Of Medicine,188665,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Secondary impacts of disease, response & control measures","Disease pathogenesis | Post acute and long term health consequences | Barriers, PPE, environmental, animal and vector control measures | Indirect health impacts",2013 +C06812,3UL1TR003167-02S2,Convalescent Plasma to Limit Coronavirus Associated Complications,"In the first awarded CTSA class, the Center for Clinical and Translational Sciences (CCTS) formed the firstmultiple-institution CTSA, with The University of Texas Health Science Center at Houston (UTHSC-H) and TheUniversity of Texas M. D. Anderson Cancer Center (UT MDACC). Since its inception the CCTS has beenachieving the primary goal of the Clinical and Translational Sciences Award (CTSA) program: to accelerateresearch to transform healthcare and train the next generation of translational scientists. Our initial proposalwas about bringing individuals and resources together, educating investigators, and building teams. In our2011 renewal we described our Lowering-The-Barriers program, which focused on removing a large number ofimpediments through initiatives such as IRB reciprocity, standard research contracts and subcontracts, clinicaldata warehouses, patient registries, and biobanks. Our efforts have been successful and aligned with thenational CTSA program. In this cycle, we bring in 3 new partner institutions to broaden and diversify ourCTSA: The University of Texas Health Science Center at Tyler (northeast Texas, rural, economicallydisadvantaged), Rice University (with strengths in computer science, education, and team science),and The University of Texas Rio Grande Valley (south Texas, education and physician resources tohelp our nearby Brownsville Clinical Research Unit perform clinical trials). Together we will effect 5strategic goals: Strategic Goal 1: To provide our investigators, staff, trainees, and scholars with theskills and knowledge necessary to advance discoveries and their translation in the new environment ofclinical and translational research (Workforce Development). Strategic Goal 2: To collaborate with allof our stakeholders in a mutually beneficial way to advance translation by furthering engagement andteam science (Collaboration/Engagement). Strategic Goal 3: To integrate pediatric and geriatricpatients, Hispanic patients with cancer, and the LGBTQ+ community into the full spectrum of clinicaland translational research (Integration). Strategic Goal 4: To advance translational science byproviding novel processes, increasing efficiency, and streamlining research (Methods/Processes).Strategic Goal 5. To create and apply innovative informatics solutions to advance translationalresearch, train the CTSA workforce, disseminate best practices, engage communities and integrateclinical and basic research data (Informatics).",2020,2024,The University of Texas Health Science Center at Houston,8681974,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2019 +C06814,3R01DA045499-03S1,Chemokine CXCL12/CXCR4 system and synthetic cathinones,"Human death in persons infected with SARS-CoV-2 (the virus responsible for the covid-19pandemic) is caused by barriers dysfunction (i.e. in the pulmonary system). Angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor of SARS-CoV-2,similarly to other coronaviruses. Surface expression of ACE2 protein was found on lungalveolar epithelial cells and enterocytes of the small intestine. In brain, ACE2 is expressed onendothelial cells, a major component of blood-brain barrier (BBB). We propose to perform aseries of studies to assess the impact of SARS-CoV-2 spike protein on BBB function in thepresence of cocaine as an extension of our funded research on psychostimulants and theCXCL12/CXCR4 chemokine system. First, a comprehensive series of experiments on theimpact of SARS-CoV-2 spike protein in the presence and absence of cocaine on brainmicrovascular endothelial cells will be performed in vitro to inform on the cellular and molecularmechanism involved in altered BBB function. Included in the analysis will be measurements ofcytosolic Ca2+ levels, mitochondrial reactive oxygen species, tight junctions and cytoskeletalproteins. Second, integrated fluorescence microscopy will be used to visualize and quantifychanges in BBB permeability in real time in awake rats after exposure to SARS-CoV-2 spikeprotein. The impact of acute and chronic administration of cocaine on BBB function in thesetting of SARS-CoV-2 spike protein will be determined. Finally, brain regions from ratsexposed to cocaine and the spike protein will be examined for levels of pro-inflammatorycytokines and chemokines. Taken together, this series of experiments will provide novelinformation about the effect of the spike protein on BBB function and neuroinflammation, and itspotential interactions with cocaine. We hypothesize that chronic cocaine exposure willexacerbate the negative impact of SARS-CoV-2 spike protein on BBB integrity and increasepro-inflammatory mediators in the CNS. These studies will provide the necessary groundwork toembark on a larger study of the impact of SARS-CoV-2 on cocaine behaviors and toxicities.",2020,2023,Temple Univ Of The Commonwealth,158500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2018 +C06815,3UL1TR002736-03S1,Convalescent Plasma to Limit Coronavirus Associated Complications: Randomized Blinded Phase 2 Study Comparing Efficacy and Safety of Anti-SARS-CoV-2 Plasma to Placebo in COVID-19 Hospitalized Patients,"PROJECT Summary: The proposed administrative supplement to the Miami Clinical and Translational Science Institute (CTSI) is arandomized blinded placebo-controlled trial to evaluate the efficacy of treatment with convalescent plasma(CP) in hospitalized patients with COVID-19. Studies have shown that CP is safe for transfusion in COVID-19patients. However, this trial was developed to obtain scientific evidence to support or reject the hypothesis thatCP may be a therapeutic option for COVID-19. The hypothesis underpinning this trial is that compared toplacebo, administration of CP will avert respiratory deterioration, the main cause of death, and improve clinicalstatus in patients hospitalized with COVID-19. This trial is being conducted across several sites that haveexperienced rapidly rising numbers of COVID-19 cases, including Miami, Florida, New York City, New York,and Houston Texas. Miami is the new epicenter of the COVID-19 pandemic in the United States, and one ofthe global hot spots. This study is within the scope of the existing CTSA award, with its focus on network trialsand rapid site initiation and team science, and leverages the Miami CTSI's focus on mobilizing resources inresponse to rapidly emerging infectious diseases, proven during the Zika virus in 2015. Miami will serve as anew site in this quickly designed and launched trial, building upon the work already done in NYC to develop amulticenter, well-powered Phase 2 trial via regional collaborations and CTSA consortium partnerships.",2020,2023,University Of Miami School Of Medicine,5391810,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2018 +C06816,3U01AI144673-02S1,"COVID-19 Epidemiology and Immune-Pathogenesis in Pregnant Women, Mothers and Children","PROJECT SUMMARY ABSTRACTDespite pandemic spread of the novel coronavirus, COVID-19, too little is known about the epidemiology ofinfection, transmission, and susceptibility to severe infection. What we do know about COVID-19 is largelybased on severe disease after infection in the elderly, and adults with co-morbid conditions. Unfortunately,susceptibility to severe infection, disease burden, and transmission in pregnant women, infants and childrenremain largely undefined. Filling these fundamental gaps in knowledge regarding infection susceptibility inthese essential developmental time points require maternal-infant cohorts capable of simultaneously screeningclinical symptoms and COVID-19 virus acquisition. The established infrastructure for two maternal-infantcohorts designed for prospective analysis of infant influenza acquisition and immunity (U01AI144673;IMPRINT) and respiratory and enteric infection (CDC sponsored PREVAIL;https://www.cdc.gov/surveillance/nvsn/prevail.html) can be leveraged to investigate the incidence, clinicalmanifestations, disease severity and immune correlates of COVID-19 infection in pregnant women, mothersand their children. The logistics are already in place for recruiting women during their third pregnancy trimester,and following the natural history of infection in infants through twice weekly symptom surveillance (by textmessaging), weekly nasal swab sampling, and virus identification in real-time through a courier network in theCincinnati metro area. Supplemental funding through this Notice of Special Interest regarding the availability ofUrgent Competitive Revision for Research on the 2019 Novel Coronavirus (2019-nCoV; NOT-AI-20-034) willexpand this analysis to include COVID-19 epidemiological surveillance for pregnant women, mothers, infantsand children (Aim 1), plus additional collection of specimens for immunological assays at the time of infectioncompared with recruitment (pre-infection) and infection-community spread resolution (Aim 2). Epidemiologicalsurveillance will include analysis of infection severity and duration of virus shedding relative to postnatal age,transmission of virus between mother and child plus other household contacts, and the potential impacts ofmaternal immunity transferred either vertically and/or postnatally through breast milk on infant COVID-19infection susceptibility. Key specimens will include PBMCs that could be used to identify gains and losses ofeach cell population, plasma/serum for analysis of qualitative/quantitative shifts in virus-specific antibodies ateach time point. An additional ""Tempus"" tube allowing stabilization of intracellular RNA from cells in wholeblood will be collected at the time of infection for gene expression analysis. We envision that as COVID-19immunological assays are being developed and become more standardized, these samples that link COVID-19infection tempo and severity of each individual will provide an invaluable resource to investigate theimmunological changes associated with asymptomatic to severe infection in pregnant women, mothers andtheir children and their relationship in each maternal-infant dyad.",2020,2023,Cincinnati Childrens Hosp Med Ctr,2530068,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity,2020 +C06817,3U24OD023319-03S1,Amplification of Racial and Social Inequalities in Response to the COVID-19 Pandemic: Impacts on Child Academic and Psychological Outcomes,"Abstract: Children are inherently shaped by the environment in which the live, learn, and play. This proposal to study theimpact of SARS-CoV-2 (COVID-19) virus outbreak on children's development brings together a multidisciplinaryteam of investigators across the country from 6 ECHO Awards, representing 5 cohorts of ~2500 middle childhoodand adolescent youth and the Person-Reported Outcome (PRO) Core). The proposed research develops andtests a novel conceptual model that casts family and community sociodemographic risk as important factors thatshape COVID-19 related school, family, and child hardships and resources that influence child positive health.We propose that school resources (e.g., type and quality of distance learning), family hardships (e.g., financialstrain and technology access), and child emotional support (e.g., connections to peers and family support)combine to predict children's positive health as measured by academic competence and psychological well-being. This ECHO proposal combines both variable-centered and person-centered methodological approachesto generate critical, time-sensitive knowledge on modifiable and actionable factors that can effectively mitigatethe impact of COVID-19 psychosocial hardships on child positive health development. As school districts,communities, and states begin planning for the next stages of economic opening and return from school closuresin the fall, it is imperative to know which children are most vulnerable and at-risk of being left behind; how schoolpolicies and teaching approaches can be best optimized; and what social and emotional supports need to be inplace in order for families and communities to ""build back better.""",2020,2023,Northwestern University At Chicago,157973,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2016 +C06818,3P51OD011104-59S2,Improving Research Resources at the TNPRC to Support COVID-19 Research,"PROJECT SUMMARY/Abstract: The Tulane National Primate Research Center (TNPRC) is one of seven National Primate Research Centers(NPRCs) sponsored by the National Institutes of Health. The Center is dedicated to providing the infrastructureand support for basic and applied research efforts to advance scientific knowledge and improve human andanimal health and wellbeing. Resources provided to core and affiliate scientists include well-characterizednonhuman primates and state-of-the-art research instrumentation.The TNPRC has one of the largest Indian-origin rhesus monkey breeding colonies in the United States. Overthe past five years, these colonies produced between 200-900 infants a year and provided close to 2,000 animalsfor biomedical research programs. Currently, there is high demand for specific pathogen free (SPF) macaqueson a national level, which requires continued availability of these resources. The TNPRC P51 base grant (P51OD011104) provides funds to support and maintain this colony, while two U42 grants and program incomederived from animal sales supply additional funds. Ongoing support for moderate expansion of the SPF colonywill continue to come from sources other than the TNPRC P51 base grant and U42 grants, including programincome from the sale of animals, construction grants, and supplements.A variety of core laboratories support TNPRC research and animal care activities, including a newly establishedHigh Containment Research Performance Core. This core includes both BSL-2 and BSL-3 spaces and operatesunder a quality assurance model to enhance rigor and reproducibility. These laboratories are equipped with high-end instrumentation used to generate high quality data from nonhuman primate research. Additional laboratoryequipment is needed to support a rapidly expanding and critically needed coronavirus research program.This supplement to the P51 base grant will be used to add one new outdoor housing enclosure, enable use ofanother existing enclosure on the breeding colony campus, and to provide funds for purchase of researchinstrumentation. The proposed breeding colony enclosures will be used to house SPF animals and have beendesigned to maximize capacity and flexibility for the available funding and to provide novel and provenenvironmental enhancement components. The addition of nonhuman primate housing and equipment resourcesfalls within the goals of the parent award. The benefits realized from these improvements will assist our effortsto enhance our capability to support core and affiliate scientists' COVID-19 research programs.",2020,2023,Tulane University Of Louisiana,2197136,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,1997 +C06819,3R01AA021746-05S1,Next Generation Rare Variant Discovery in Multiplex AD Families,"The World Health Organization (WHO) is currently reporting 4,793,076 confirmed cases ofCOVID-19 infection world-wide with 316,341 deaths. With each new pandemic the population is atrisk until vaccines and medications can be developed. Quarantine of the entire population appearsto be only alternative until sufficient time elapses for vaccine development. Therefore, animportant public health goal is to determine who must be sheltered in place and who can resumenormal activities. Older individuals appear to be disproportionately adversely affected by thevirus. Although immune functioning tends to wane with age, genetic and lifestyle factors appear togreatly alter susceptibility. The goal of this project is to identify individuals who may be more orless resilient due to their lifetime use of alcohol. Those with an alcohol use disorder (AUD) mayhave a greater risk for adverse consequences of SARS-CoV-2 exposure, yet low doseconsumption may improve immune functioning. A better understanding of whether alcohol use hasa different effect at low doses than at high doses is critical to public health campaigns that advisethe public on safe use of alcohol. Genetic variation in the Major Histocompatiblity Locus (MHC)located on chromosome 6 plays an important role in immune functioning. Variation in the humanleucocyte antigens (HLA) have been significantly associated with many diseases and hold promisefor personalized antigen-specific disease prevention. Having this information available, as part ofroutine medical screening in the future, would enable us to stratify the population into thoseneeding sheltering in place and those who do not. This project would determine the feasibility ofusing HLA gene variation along with screening for alcohol use as an important part of stratifyingthe population at the onset of viral epidemics. The present proposal builds on existing resources from participants for whom exomesequencing and/or HLA serology was completed and utilizes the extensive alcohol use histories,psychiatric diagnoses, and health histories obtained at baseline. New interviews concerningalcohol use, both distal and proximal, current health status, and exposure histories for the SARS-CoV-2 virus will enable us to determine their contribution to infection and progression. We willcontrast those with AUD with those without and unaffected members of high risk versus low riskfamilies in (Aim 1). In Aim 2, we will assess levels of recent and past alcohol consumption to viralresponse. Genetic variation in the major histocompatibility complex (HLA) region will be tested forassociation with outcome among those that are demonstrated to have been exposed (Aim 3).",2020,2021,University Of Pittsburgh At Pittsburgh,156267,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2015 +C06821,3UH3OD023271-05S1,Prenatal and Early Childhood Pathways To Health: An Integrated Model of Chemical and Social,"Abstract: Children are inherently shaped by the environment in which the live, learn, and play. This proposal to study theimpact of SARS-CoV-2 (COVID-19) virus outbreak on children's development brings together a multidisciplinaryteam of investigators across the country from 6 ECHO Awards, representing 5 cohorts of ~2500 middle childhoodand adolescent youth and the Person-Reported Outcome (PRO) Core). The proposed research develops andtests a novel conceptual model that casts family and community sociodemographic risk as important factors thatshape COVID-19 related school, family, and child hardships and resources that influence child positive health.We propose that school resources (e.g., type and quality of distance learning), family hardships (e.g., financialstrain and technology access), and child emotional support (e.g., connections to peers and family support)combine to predict children's positive health as measured by academic competence and psychological well-being. This ECHO proposal combines both variable-centered and person-centered methodological approachesto generate critical, time-sensitive knowledge on modifiable and actionable factors that can effectively mitigatethe impact of COVID-19 psychosocial hardships on child positive health development. As school districts,communities, and states begin planning for the next stages of economic opening and return from school closuresin the fall, it is imperative to know which children are most vulnerable and at-risk of being left behind; how schoolpolicies and teaching approaches can be best optimized; and what social and emotional supports need to be inplace in order for families and communities to ""build back better.""",2020,2021,University Of Washington,294760,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2016 +C06822,3U01AI148108-01S1,Host Factors in Response to Therapeutic Monoclonal Antibodies and Vaccination,"PROJECT SUMMARY. Effective responses in Fc-dependent, antibody-mediated anti-viral host defenserequire efficient and productive interactions between the cell-type specific Fc receptors of the host and anti-SARS-CoV-2 antibody. The apparent lack of effective responses in some patients represents both anopportunity and a critical challenge to delineate the mechanistic basis for such differences. Genetic inquiry canidentify the contributions that the host brings to these differences. Preliminary data, presented in our parentU01, indicate that nearly one-third of persons have structural variants (SV) in the classical Fc locus in additionto the prevalent single nucleotide polymorphisms affecting affinity of ligand binding, receptor mobility in theplane of the cell membrane and quantitative receptor expression. These larger SVs affect Fc receptors onboth lymphoid and myeloid cell series, and nearly a third are uncharacterized in terms of genomic structure,resultant alterations in protein structure and impact on net biological function. Furthermore, persons of African-American heritage are over-represented in a number of these novel variant clusters. Current genotyping andwhole genome sequencing efforts (eg, COVID-19 hg; COVIDhge) are unable to identify and define these SVsbecause of the segmental duplication of the FCGR locus with >98% homology of the paralogs. New,innovative technical approaches involving CRISPR/Cas9 targeted excision of the paralogs, coupled with long-read sequencing, now enable resolution of novel structural variations impacting biological function. Suchknowledge will present the exceptional opportunity to enhance our understanding of disparities in COVID-19disease, to anticipate the host response and potentially to adjust vaccination protocols. Accordingly, the goalsof this supplement are to 1) immediately implement and apply our CRISPR/Cas9 digestion strategy and long-read sequence technology of Aim 1b to an expanded number of individuals originally proposed emphasizingethnic minorities disproportionally affected by the COVID-19 pandemic, 2) expand the number of variantclusters to include all those found in African-American donors, 3) sequence the FCGR region in 100 patientswith severe COVID-19 phenotype drawing on biospecimens drawn from across the Deep South, and 4)accelerate the analysis of sequencing data to identify the novel architectures and begin development ofscalable genotyping strategies for detection of SVs and SNPs that are predicted to impact Fc receptorfunction/expression and influence the host response to acquired humoral immunity in both the acute andconvalescent phases of disease. These goals will be enabled our COVID-19 Enterprise biobank andbiospecimens from across the Deep South through our CTSA-driven CCTS Partner Network and will directlyimpact on our ability to identify individuals more or less likely to respond to effector antibody production.",2020,2022,University Of Alabama At Birmingham,222725,Human Populations,Other | Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +C06823,1R21AI158997-01,Accurate prediction of neutralization capacity from deep mining of SARS-CoV-2 serology,"Abstract: The goal of this project is to establish an accurate and sensitive method for predicting the neutralizationcapacity against SARS-CoV-2 of serum samples by deep mining of antibody profiles. The COVID-19 pandemicremains a global threat with nearly seven million cases and 400K deaths. In the absence of effective vaccinesand therapeutics, immunity against SARS-CoV-2 is a main mechanism of protection against SARS-CoV-2(re)infection. Our recent studies of convalescent serum samples revealed that their levels of neutralizationcapacity vary greatly (over 100-fold) and only a small subset has high neutralization capacity. Because viralneutralization assays are inherently low throughput, it is unrealistic to apply it to a high-risk population such ashospital workers in a timely manner. Unfortunately, there is only moderate correlation between theneutralization capacity and the level of anti-SARS-CoV-2 antibody levels determined using standard ELISA.Clearly, we still do not understand what types of antibodies contribute to viral neutralization. Our overarchinghypothesis to be tested in this project is that by examining the antibody profile in patient serum more deeplyand quantitatively in terms of antigens, epitopes and antibody types, we will be able to identify quantitativepredictive markers for viral neutralization. To this end, we will develop multiplex assay for SARS-CoV-2serology that will enable us to deeply characterize the antibody profile. We will then develop a predictivealgorithm by utilizing. We have assembled a team of experts with truly complementary skills in antibodycharacterization, virology and data mining. We have access to a large number of convalescent serum samples,which will enable us to critically validate our technology. We will expeditiously execute the following aims. (1)We will develop multiplex serology assay for SARS-CoV-2 that can profile up to 15 antibody-antigeninteractions in a single reaction. The main technical innovation is the introduction of multi-dimensional flowcytometry. We will produce multiple antigens including Spike, receptor-binding domain and nucleocapsidprotein, and their natural and designed variants. We will refine and validate the assay using a large panel ofconvalescent serum samples. (2) We will develop an improved viral neutralization assay to better quantify theneutralization capacity. (3) We will develop a predictive algorithm for neutralization capacity that utilizes theantibody profiles from our multiplex assay. This analysis will identify serology parameters that contribute toneutralization. The end products of this project will include a high-throughput serology assay that gives far-richer antibody profiles than the current standard accompanied with an accurate predictive algorithm. Together,this platform will help advance a fundamental understanding of SARS-CoV-2 infection as well as thedevelopment of vaccines and therapeutics against this formidable pathogen.",2020,2022,New York University School Of Medicine,466125,Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics | Immunity,2020 +C06824,3U01AG064948-02S1,Harmonized Diagnostic Assessment of Dementia (DAD) for Longitudinal Aging Study of India (LASI)-Genomic study,"Project Summary: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) isthe first and only nationally representative and publicly available dataset on late-life cognition and dementia inIndia. It administers the Harmonized Cognitive Assessment Protocol (HCAP) that is designed to beharmonized with ongoing longitudinal studies of aging around the world, including the Health and RetirementStudy (HRS) in the United States, and prior studies in India. This rich set of cognitive phenotypes and a varietyof other health and social environment phenotypes, as well as genotype data from whole genome sequencing,give us a unique opportunity to identify the mutational spectrum underlying risk of dementia and AD in arepresentative sample of India. In this application, we aim to monitor and investigate the impacts of Coronavirus Disease 2019 (COVID-19)on the LASI-DAD households through phone surveys. The COVID-19 pandemic will fundamentally alter thelives of individuals across the world, and India is not an exception. To gain insight into the health and economicimpacts of the pandemic, we propose to track the LASI-DAD households and conduct quarterly phoneinterviews for 1-year. Through continuous monitoring, we will assess how individuals' knowledge, attitudes,and behaviors related to the disease change over time, as well as the health and economic impacts of thepandemic. The collected data will be linked to the follow-up Wave 2 LASI-DAD for the estimation of theirimpacts on cognitive changes and dementia incidence.",2020,2024,University Of Southern California,360284,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,South-East Asia,South-East Asia,Data Management and Data Sharing,,,India,India,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2019 +C06825,3UH3OD023389-05S2,The Early Growth and Development Study Pediatric Cohort,"Abstract: Children are inherently shaped by the environment in which the live, learn, and play. This proposal to study theimpact of SARS-CoV-2 (COVID-19) virus outbreak on children's development brings together a multidisciplinaryteam of investigators across the country from 6 ECHO Awards, representing 5 cohorts of ~2500 middle childhoodand adolescent youth and the Person-Reported Outcome (PRO) Core. The proposed research develops andtests a novel conceptual model that casts family and community sociodemographic risk as important factors thatshape COVID-19 related school, family, and child hardships and resources that influence child positive health.We propose that school resources (e.g., type and quality of distance learning), family hardships (e.g., financialstrain and technology access), and child emotional support (e.g., connections to peers and family support)combine to predict children's positive health as measured by academic competence and psychological well-being. This ECHO proposal combines both variable-centered and person-centered methodological approachesto generate critical, time-sensitive knowledge on modifiable and actionable factors that can effectively mitigatethe impact of COVID-19 psychosocial hardships on child positive health development. As school districts,communities, and states begin planning for the next stages of economic opening and return from school closuresin the fall, it is imperative to know which children are most vulnerable and at-risk of being left behind; how schoolpolicies and teaching approaches can be best optimized; and what social and emotional supports need to be inplace in order for families and communities to ""build back better.""",2020,2023,University Of Oregon,310064,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2016 +C06826,3UH3OD023344-04S1,"Understanding Risk Gradients from Environment on Native American Child Health Trajectories: Toxicants, Immunomodulation, Metabolic syndromes, & Metals Exposure","Project Summary: Available knowledge about how stress in the home environment influences child neurodevelopment points tothe importance of capturing time-sensitive data on major stressors, such as the COVID-19 pandemic, acrossthe many populations represented in ECHO. The collective ECHO data offers insight into an unfortunatenatural experiment on how such a major stress affects ECHO children and families. Understanding this willallow for better preparation to meet the needs of affected children as they re-enter school and community life,while helping to mitigate the impacts of similar stressors in future disasters affecting children. Minority andmarginalized populations are representative of US population prevalence in ECHO, but the total number of anygroup within the 55,000 ECHO children may still be relatively small. For example, most Native American ECHOparticipants are in 2 cohorts, and represent fewer than 1500 of the 55,000 children in ECHO. It is conceivablethat time-sensitive measures such as responses to ECHO will be captured in very few, or none, of the ECHOparticipants within marginalized populations most affected.This ECHO NOSI application examines the relative pandemic-induced stress across multiple cohorts differingwith respect to marginalization, COVID-19 population prevalence, and experience with historicaltrauma/systemic racism. At present, this comparison includes the Navajo Birth Cohort Study/ECHO(NBCS/ECHO) cohort, the PASS ECHO cohorts (Indigenous and non-Indigenous populations in SouthDakota), and the Atlanta ECHO cohort of urban Black participants. We propose three aims to address ouroverall hypothesis that pandemic-induced stress will be greatest in populations experiencing the greatest ratesof infection and mortality, but exacerbated by historical trauma in Indigenous and Black populations. Aim 1 willensure availability of time-sensitive data to test this hypothesis in the future; Aim 2 will expand theopportunities for remote and lay staff collection of neurodevelopmental data to ensure availability for testing thehypothesis, and Aim 3 will test and develop a reliable system for transfer of NBCS data to the DAC NBCSportal at greater frequency than is currently possible with infrastructure limits.This is the first study exploring the impact of increased stress across communities already affected by historicaltrauma and facing a disaster like COVID-19 to address whether collective stress affects long-term childneurodevelopment through changes in parenting and the home environment, and will ensure minority cohortsare represented in the time-sensitive datasets in sufficient numbers to evaluate and compare impacts todevelop mitigation interventions, rather than simply by population proportional representation.",2020,2023,University Of New Mexico Health Scis Ctr,320875,Human Populations,Black | Other,Children (1 year to 12 years),Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2016 +C06827,3R01AG059546-02S1,Developing an Online Tai Ji Program to Improve Health Outcomes in Older Adults,"Project Summary/AbstractBackground. The ongoing COVID-19 public health crisis is significantly impacting older Americans who are athigher risk for severe illness from novel coronavirus infection. The implementation of shelter-in-place andsocial distancing, though an essential step in reducing transmission of the virus, has imposed unintendedpersonal life hurdles and major social constraints on cognitively impaired older adults. Many of theseindividuals are dependent on community-based services for care and support and therefore face greatchallenges to performing essential social activities, including attending community-based exercise classes.Given that the signs of the outbreak abating are still vague and that there is the likelihood of new outbreak thiswinter, the continued enforced societal isolation will exacerbate sedentary behaviors in a population withalready low levels of physical activity and poor physical and mental health outcomes. Objectives. Thisapplication requests Administrative Supplement to support the development and testing of an Internet-basedexercise intervention (Tai Ji Quan Moving to Improve Brain Health [TJQMIBH]) using real-timevideoconferencing for older adults with mild cognitive impairment (MCI). The proposed work aligns with thescope of our parent project (AG059546), which is designed to evaluate the efficacy of an in-person, group-based, cognitive-motor-integrated Tai Ji Quan intervention for this vulnerable and at-risk population. The fundsfrom this Administrative Supplement will support research work related to the following four specific aims:Specific Aim 1: to transform the in-person TJQMIBH intervention protocol into a deliverable online classprotocol; Specific Aim 2: to pilot test the online TJQMIBH virtual class delivery protocol in older adults withMCI; Specific Aim 3: To develop effective and protected online assessment and data ascertainmentprocedures encompassing the cognitive and physical performance measures; and Specific Aim 4: to conducta randomized controlled trial comparing the effectiveness of the virtual TJQMIBH intervention with a stretchingexercise control group among older adults with MCI. Significance and Impact. Shelter-in-place and social-distancing policies in response to COVID-19 have left older adults with cognitive impairment with few or noopportunities to continue physical activity in their community. Evidence suggests that limited or no physicalactivity may lead to an increased risk and potential worsening of chronic health conditions for this at-riskpopulation. Meanwhile, there are few Internet-based exercise programs available to keep older adults activeand healthy in the highly contagious COVID-19 environment. Our project addresses this urgent public healthneed by developing and delivering a virtual exercise program at home through the Internet. If successful, theoutcome from this project will exert a sustained, powerful influence on the field of disease prevention byproviding a safe, accessible, and effective exercise intervention for older adults with cognitive impairment thatcan be implemented both under current extreme conditions and in the aftermath of the COVID-19 pandemic.",2020,2024,Oregon Research Institute,396468,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health | Innovation,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C06828,3R01MH121079-02S1,"COVID-19 supplement to a computational examination of threat and reward constructs in a predominantly low-income, longitudinal sample at increased risk for internalizing disorders","Abstract: The novel Coronavirus (COVID-19) pandemic has had a far-reaching impact on the US population, and hasdisproportionately affected race-ethnic minorities, individuals living in or near poverty, and those living in largeurban areas. Based on past literature we expect COVID-19 related stressors to have large negative effects onmental health, but we do not yet understand how social and economic factors might moderate those effects.The current supplement would add time-sensitive data by collecting real-time online surveys of both targetyoung adults and their parents (n=1,200) in a representative sample of a disadvantaged population. To betterunderstand how major stressors, like the COVID-19 pandemic, are moderated, we must assess these social,occupational, economic, health, and mental health impacts as they happen, across different cities/states (withdifferent pandemic policies) and in those most at-risk for poor outcomes: low-income and minority families andyoung adults who are showing disparities in infection and mortality. Thus, by adding this critical, time-sensitiveassessment, we will be even better positioned to understand how adversity shapes the ongoing developmentof RDoC threat and reward circuits, as well as a broader assessment of how COVID-19 is impacting mentalhealth in marginalized, low-income, minority populations. Moreover, we will document the way in whichresilience factors including social support, economic policies, and family resources moderate the negativeeffect of COVID-19 related stressors on mental health. This builds on the parent grant's focus to use data-driven analytics and hypothesis testing to validate multilevel-multimodal models of Threat and Rewardconstructs in an existing representative longitudinal cohort at risk for psychopathology and to delineate how ahistory of exposure to adversity links to these domains. The parent grant is assessing 600 young adults twice(at age 20 and 24) from The Fragile Families and Child Wellbeing Study (FFCWS), an ongoing study of 4900children born 1998-200 in large US cities. Attributes of the FFCWS are: 1) parents and children were surveyedand assessed at birth, 1, 3, 5, 9, 15 years; 2) the sample is nationally representative; 3) Substantial enrichmentfor low-income (median income to needs ratio=1.4) and minority families (66%), populations are often under-represented in research; and 4) participants are entering early adulthood, a period of heightened risk forpsychopathology. Because of the unique social distancing required by COVID-19, having data from multiplefamily members will be particularly powerful in understanding the economic and social, and in turn, mentalhealth consequences of COVID-19. To predict internalizing symptoms, we will identify biotypes cross-sectionally and longitudinally. Socio-ecological conditions will be deeply assessed (including COVID-19-relatedadversity, prior public assistance, COVID-19 related public assistance and policies) and used to forecast theonset/intensification of internalizing symptoms at multiple units of analysis from brain to behavior to symptoms.",2020,2024,University Of Michigan At Ann Arbor,155961,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C06829,3UH3OD023348-05S2,"RACE, COVID-19, and Health Outcomes Among Individuals Born Preterm","Abstract: This project addresses a critical gap in the understanding of potential links between race, the COVID-19pandemic, and the well-being of children. We will evaluate these relationships by collaborating with other ECHOcohorts, thus increasing the geographical variation of our study sample. Our cohort, derived from the ExtremelyLow Gestational Age Newborn (ELGAN) study, provides the opportunity to evaluate relationships within subsetsdefined in terms of gestational age at birth. Given the high prevalence of early life adversities among individualsborn extremely preterm, we anticipate finding increased vulnerability to the harmful effects of the COVID-19pandemic. Although fewer children than adults have developed life-threatening infections due to COVID-19, thepublic health policies implemented to stop the spread of COVID-19 have disrupted children's lives througheconomic depression, social distancing, and unprecedented educational disruptions. The shift to distancelearning has changed children's home, school, and social environments, but we know very little about the impactof these changes on children's health and development. These disruptions may have stronger negative effectson historically underserved groups, including lower income families, as well as racial and ethnic minorities. Thisproposal seeks to evaluate the unintended psychosocial impacts of COVID-19 public health policies on childrenand families, and to examine if these effects are more prominent within lower income communities andcommunities of color. We examine if COVID-19 Health Policies impose more hardships on families within thesegroups, and if these hardships adversely affect their positive health development, as indexed by academiccompetence and well-being. By collaborating with cohorts comprised primarily of children born near or at term,we will also evaluate whether COVID-19 related stressors have greater impact on a particularly vulnerable groupof children, i.e., those born extremely preterm. Further, we will examine if school practices related to distancelearning and supportive social networks are also associated with child outcomes, independent of COVID-19hardships. This project will identify processes by which public health policies influence families and will identifypractices that promote children's positive health development.",2020,2023,University of North Carolina at Chapel Hill,311000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Other secondary impacts,2016 +C06830,3UH3OD023285-05S2,Prenatal Exposures and Child Health Outcomes: A Statewide Study,"Project Summary: Evidence from epidemiologic studies demonstrates the negative effects of both chronic and acute stress duringgestation. These effects may occur perinatally or later in the child's life. The COVID-19 global pandemic has ledto unprecedented mass disruption of social and financial security as well as changes in medical care delivery.These conditions are causing elevated levels of distress even for portions of the population that may havepreviously been protected from psychosocial stress. Of particular concern for pregnant women and their children,there may be direct biological effects related to infection with SARS-CoV-2 as well as substantial indirectpsychosocial effects during critical periods of development with long-lasting impact on children relevant to theEnvironmental Child Health Outcomes (ECHO) program. This proposal addresses how psychosocial stressrelated to the COVID pandemic may impact perinatal and neurodevelopmental outcomes. Furthermore, evidencesuggests that psychosocial stress is associated with both the gastrointestinal and vaginal microbiomes.Therefore, we will determine if maternal microbiomes or infant microbiomes mediate the impact of psychosocialstress on perinatal and neurodevelopmental outcomes. In aim 1, we address the maternal microbes and theirrole in mediating perinatal outcomes caused by maternal psychosocial stress during pregnancy. In aim 2, wefocus on maternal psychosocial stress and its impact on neurodevelopment as mediated by the changes to theinfant microbiota. We will examine these objectives in the context of our ongoing work, and as an extension ofthe parent grant (UG3/UH3OD023285, Paneth), where our organizing principle is that for many environmentalexposures the most sensitive period of risk for child health is pregnancy and the perinatal period. The parentgrant explores three primary exposures: toxic, nutritional, and inflammatory in a stratified random sample of statebirths recruited in the first trimester of pregnancy. Of the planned 1,100 new enrollments of cohort dyads intoECHO, more than 700 pregnant women have been consented, and, with a 75% follow up rate, more than 400children have already been seen in infancy. Over 300 women are expected to be enrolled during the projectperiod. While this research will leverage the local ECHO cohort, the project is designed to engage ECHO teamscience through two distinct but complementary ECHO-wide projects: (1) incorporation of data from two cohorts(O'Conner & Deoni) to address the aims proposed above and (2) provision of data and biospecimens to separateCOVID supplement (Transande) which addresses SARS-CoV-2 seropositivity/COVID illness as well aspsychosocial stress (assessed via questionnaire and cortisol measured in hair) as they relate to shortenedgestation and other perinatal outcomes. Our efforts will not only inform the specific hypotheses being tested butwill also inform ""touch-free"" methods for sample collection and patient interaction. The work proposed hereincomplements the parent grant by addressing an exposure (maternal psychosocial stress during a time ofpandemic), not included in the parent grant, and at least two of ECHO's outcomes (PPP and neurodevelopment).",2020,2021,Michigan State University,305679,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2016 +C06831,3R01CA226570-02S1,Aggressive prostate cancer of African Americans is correlated with regulation of Immunoregulatory Genes in stroma,"PROJECT SUMMARY/ABSTRACT Recent studies indicate that patients with metastatic cancer experience more severe outcomes of SARS-CoV-2 (COVID-19) virus infections compared to those with non-metastatic carcinomas and patients withoutcancer, possibly due to their compromised immune systems. According to the Centers for Disease Control andPrevention, African Americans (AA) suffer from the virus at higher rates than the European American (EA)population of the US. The mechanisms of how ethnicity contributes to higher SARS-CoV-2 infection rates andincreased disease severity are unknown, but genetic/epigenetic components (in addition to socioeconomicfactors) often play a role in disease progression and response to therapies. As an example, prostate cancer(PCa) in AA is diagnosed at an earlier median age and in a more advanced stage than PCa of EA, with poorerprognosis and significantly higher mortality. These differences persist even after accounting for socioeconomicand environmental factors. In our parent grant, NIH/NCI R01CA226570 ""Aggressive prostate cancer of AfricanAmericans is correlated with regulation of immunoregulatory genes in stroma"", we propose an epigenetic controlof the antiviral immune response pathways in prostate stromal cells as one of the reasons for differences inprostate cancer progression among patients. We observed that the antiviral immune responses to endogenousretroviruses (ERVs) activate type 1 interferons (IFNs) that in turn increase transcription of interferon-stimulatedgenes (ISGs) in tumor-adjacent stroma, as measured by RNA levels in tumor-adjacent cancer-associatedfibroblasts (CAFs). This stimulation proceeds more strongly in EA than in AA. Furthermore, mRNA markers ofactivated dendritic cells (DCs), which are part of the antitumor immune response, were also more prevalent inEA than in AA tumor-adjacent stroma. These processes have each been associated with improved outcome inseveral solid tumors, making this antiviral pathway a potential target for an activation therapy. DCs are immune cells that produce IFNs and can have antitumor as well as antiviral activity, includinganti-SARS-CoV-2. In this administrative supplement application, we hypothesize that cancer-associatedalterations in the function of DCs affect the response to SARS-Co-V2 among cancer patients, especially in thosewith aggressive disease. These alterations may be different (and have different outcomes) in AA patientscompared to EA. We further hypothesize that antiviral immune response pathways in cancer patients infectedwith SARS-CoV-2 can be activated using the nucleotide analog 5AzaC, a methyltransferase inhibitor, incombination with vitamin C, which increases the viral mimicry induced by 5AzaC. We will test our hypotheses in two aims. First, we will investigate whether and how the antiviralimmune response to SARS-CoV-2 is exacerbated by race and cancer, and second, we will determinewhether AA and EA CAFs treated with a combination of 5AzaC and vitamin C can enhance antiviralresponses of DCs to SARS-CoV-2. Impact: In addition to suppressing tumor growth, the proposed immune-stimulating combination therapywith 5AzaC and vitamin C may also activate immune responses to SARS-CoV-2 infection by galvanizing anti-viral immune response pathways in both the tumor and the DCs.",2020,2021,University Of California-Irvine,78500,Human Populations,Other,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Prophylactic use of treatments,2019 +C06832,3R01AA025720-03S1,The Impact of COVID-19 among Recent Latinx Immigrants: Examining Opportunities for Intervention,"Abstract Emerging evidence reveals the disproportionate impact of COVID-19 on the US Latinx immigrantcommunity. Concern for the consequences of COVID-19 is especially high among the Latinx population inMiami-Dade County, the most populous county in Florida. As of April 24, 35% of all reported COVID-19 casesin the state of Florida (10,926), 27% of deaths (287), and 30% of persons hospitalized (12,465) were residentsof Miami-Dade County. Given that Miami-Dade is at epicenter of the COVID-19 pandemic in the state ofFlorida and the majority of its 2.8 million residents are Latinx immigrants, there is an urgent need to explore theimpact of COVID-19 in this population. Latinx immigrants face increased challenges related to employment,financial strain, access to care, limited social support systems, language barriers, and fears related toimmigration status that create barriers to adherence of COVID-19 containment and mitigation efforts, and couldexacerbate downstream health effects such as mental health and substance use problems. The relative effecton recent Latinx immigrants, many of whom have experienced forced migration and are struggling to adapt to anew host country, may be particularly devastating. The proposed study addresses this urgent need by leveraging an ongoing NIAAA-sponsored longitudinalstudy set (currently in the second wave of data collection). Specifically, the study will administer asupplemental COVID-19 protocol to our already engaged sample of recent Latinx immigrants. This data will bemerged with pre- and post-pandemic data currently being collected via the parent study. The overarching aimof the proposed study is to (1) examine adherence and attitudes to COVID-19 containment and mitigationefforts and (2) how sociocultural factors coupled with COVID-19 related stress impacts changes in alcohol andother drug use and adverse mental health outcomes in this population. This research would immediatelyleverage the parent study cohort, infrastructure, and existing protocol to rapidly assess the impact of theCOVID-19 pandemic in this vulnerable Latinx subgroup. This knowledge will be critical to informing earlyresponse procedures with the power to mitigate deleterious COVID-19 adherence and mitigation efforts,pandemic stressors, and subsequent downstream health consequences such as alcohol and other drug useand adverse mental health outcomes in this population. Additionally, knowledge gained from the proposedstudy can be utilized to examine the impacts of COVID-19 on the original study outcomes (i.e., impaireddriving, transportation). Findings from this investigation can prove to be invaluable in understanding thebehavioral changes triggered by COVID-19 among recent Latinx immigrants, and informing effective policiesand culturally relevant outreach strategies that can be applied in the face of future pandemic recurrences.",2020,2023,Pacific Institute For Res And Evaluation,144794,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Social impacts,2018 +C06833,3R01MH095507-10S1,Delivery of integrated PrEP and ART for HIV prevention for couples in Kenya,"Abstract: Maximizing access is one of the key challenges for optimizing the public health impact of pre-exposureprophylaxis (PrEP) for HIV prevention. The coronavirus disease 2019 (COVID-19) epidemic has overwhelmedhealth systems globally. In Africa, PrEP has been added to an already-burdened health infrastructure, and theoverlay of COVID-19 threatens derail the tremendous progress made with HIV treatment and prevention,including provision of PrEP. Since 2017, in collaboration with the Kenyan Ministry of Health, we have beenconducting a large step-wedge randomized roll-out of PrEP delivery in 24 high-volume, PEPFAR-supported,public HIV care facilities, using detailed data Abstract: Ion from clinic records and implementation science methods(including the RE-AIM framework), plus training and technical assistance in another ~70 clinics outside of therandomized trial (together, the work is called the Partners Scale-Up Project). We have found high enthusiasmamong providers and clients, with good uptake, continuation, and adherence for PrEP and clinic-initiatedadaptions that may PrEP delivery more efficient. During the current COVID-19 emergency, we have continuedremote provision of technical assistance to monitor implementation progress and cross-pollinate best practicesacross clinics. We are hearing that health providers feel ill-prepared to manage or screen for COVID-19 butnevertheless remain committed to serving clients. Clinics have rapidly accelerated adaptations to continueservices provision, including dispensing longer PrEP refills, quickly initiating one-stop provision of PrEP services(to minimize staff-client contact), and shifting PrEP services to HIV testing centers and potentially to community-based delivery. Incredibly, PrEP initiations/refills are continuing at a rate similar to 2019. Thus, we hypothesizethat despite the alarming implications for individuals and health systems of the COVID-19 emergency, there isboth resilience of public health clinic staff and opportunity for health systems to adapt and innovate efficientstrategies for provision of critical services. In this administrative supplement, we propose to add a novel aim (Aim5) to explore the impact of COVID-19 on PrEP services, specifically clinic adaptation and staff resilience. Wepropose to document and accelerate rapid adaptations in PrEP services across the ~100 clinics across Kenyain our network, using our technical assistance model to cross-pollinate best practices that mitigate COVID-19impacts. Qualitative interviews will explore provider distress and identify key components of resilience and PrEPservice adaptation. The work is fully within the scope of our ongoing project, which has explicit goals ofunderstanding barriers and facilitating innovations for PrEP delivery for providers and health systems. Given ourrobust technical assistance network and data collection systems (including phone/video interviews), this workcan begin immediately and will be translatable to PrEP delivery across Africa during this public health emergency.",2020,2021,University Of Washington,147098,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Nurses and Nursing Staff | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Africa,Africa,,,,South Africa,South Africa,"Secondary impacts of disease, response & control measures",Indirect health impacts,2011 +C06834,3R01MH120597-02S1,Adapting Coordinated Specialty Care in the Post COVID-19 Era,"Coordinated Specialty Care (CSC) programs provide evidence-based services for young people withrecent onset of a psychotic disorder. New York State's program, OnTrackNY is a nationally recognized modelof CSC treatment. OnTrackNY provides coordinated, team-based services and has demonstratedimprovements in symptoms, functioning, hospitalization, and work/school participation. The rapid rise ofCOVID-19 has created shocks to the health care system, producing numerous rapid changes in behavioralhealth service delivery, including telehealth, in the absence of guidance from evidence or experience. It isunclear how these changes will impact the need for and delivery of psychiatric care and client outcomes. OnTrack Central, an intermediary organization responsible for training and implementation support ofOnTrackNY programs, has created systems for multi-level stakeholder engagement, a centralized datacollection protocol for quality improvement and evaluation of program fidelity, and a mechanism to supportpractice based-research. Our daily engagement of the OnTrackNY network has revealed how recent changesare dramatically impacting CSC services. In 2019, OnTrackNY was awarded a hub within the Early Psychosis Intervention Network (EPINET) toadvance a learning health care system (LHS). The breadth of OnTrackNY sites coupled with OnTrack Centraloversight provides an opportunity to examine the impacts of the COVID-19 crisis in New York State. Thediversity of the 23 OnTrackNY teams located throughout the state enables examination of settings with highand low prevalence of COVID-19 infections and diverse regulatory and workforce environments. TheOnTrackNY network includes programs that operate within variable regulations (outpatient clinics at communityagencies, state-operated facilities, and community and academic hospitals in urban, suburban, and ruralareas) with very diverse participant populations. This project will examine the implications of modifications to service delivery within the OnTrackNY LHSduring and after the COVID-19 crisis. We will use the implementation science framework, Framework forReporting Adaptations and Modifications-Enhanced (FRAME) to systematically evaluate modifications madeand ascertain their impact. We will utilize integrative mixed methods, including qualitative interviews and focusgroups with stakeholders (clients, families, providers and decision makers at the state and local levels) andanalysis of OnTrackNY program data The project aims to assess: 1) the implications of governmental andagency level policy changes and how these decisions impact team staffing and functioning; 2) implications fordelivery of CSC services; and 3) impact on client-level care processes (e.g. utilization of services) andoutcomes. The goal is to develop a CSC Model Adaptation Guide that will be fidelity-consistent, andassociated with consistent engagement, service utilization or favorable outcomes of care.",2020,2024,Columbia University,324329,Human Populations,Unspecified,Adolescent (13 years to 17 years),Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Policy research and interventions | Indirect health impacts | Health leadership and governance | Systemic/environmental components of capacity strengthening,2019 +C06835,3UL1TR002369-04S2,Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C),"The Oregon Clinical and Translational Research Institute (OCTRI) has been accelerating research at OregonHealth & Science University since 2006. Its many highly functional programs assist investigators and traineesby providing diverse services. Here, we propose that OCTRI will transition to retain our strengths, but alsobecome a key hub in the national network, by focusing on five crosscutting aims. These align closely with thegoals of the Funding Opportunity Announcement, and the goals outlined by NCATS for the CTSA program inan ideal state. OCTRI's overall aims are to:Overall Aim 1: Catalyze Clinical and Translational Research.Overall Aim 2: Enhance Partnerships with Communities.Overall Aim 3: Foster and Support Scientific Collaboration.Overall Aim 4: Expand the Translational Workforce for the 21st Century.Overall Aim 5: Cultivate Innovation in Research.We have organized a highly functional leadership structure to enable us to meet these goals, and will seek theguidance of several advisory groups. We will catalyze research by developing and supporting new informaticsapproaches that both integrate the clinical care enterprise with the research enterprise and facilitate therecruitment of patients into clinical trials, locally and across the CTSA network. We will engage diversestakeholders in the translational research process, by partnering with OHSU investigators, communitycoalitions, and business enterprises. We will foster team science through local awards to trainees and toemerging investigators. We will partner with regional institutions to foster community-engaged research, toenhance the diversity of trainees, and to provide opportunities in biomedical research not available at otherinstitutions. We will train clinical and translational scientists and research staff for the next generation, byfocusing on the skills and attitudes necessary for research in the future. At all steps, we will measure outcomesand, when necessary, ""turn the curve.""",2020,2022,Oregon Health & Science University,100000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2017 +C06836,3UM1AI068635-14S2,"CoVPN 3001 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine SDMC","Project Abstract: This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) VaccinesLeadership Operations Center (LOC) for implementation of the first COVID-19 vaccine efficacy trial ""A Phase3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, andImmunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older.""With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 inSARS-CoV-2 infected individuals. Addressing this gap, the HVTN has joined 4 other National Institute ofHealth (NIH) clinical trial networks to form the CoVPN, an enhanced network dedicated to developing globallyeffective vaccines for SARS-CoV-2. Due to its extensive experience implementing HIV vaccine trials, the HIVVaccine Trials Network (HVTN) LOC was selected to as the CoVPN vaccine LOC.This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of mRNA-1273 SARS-CoV-2, a lipid co-formulated messenger ribonucleic acid (mRNA) vaccine encoding the SARS-CoV-2 spike protein(S), to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from clinicaltrial sites across the US, using data analytics to target high risk individuals with a diverse racial and ethnicprofile. In addition, the CoVPN will use accessory community-based sites, staffed by clinical teams from thehome sites and employ mobile clinics to enroll individuals in new high risk settings (e.g., meat packing plants).Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will bemonitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals whoprogress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will bedone at CoVPN laboratories, using validated assays for diagnosis and immune monitoring.Specific aims of this study are to demonstrate efficacy of mRNA-1273 SARS-CoV-2 to prevent COVID-19, toevaluate the safety and reactogenicity of 2 injections given 28 days apart, the assess the ability to preventinfection with SARS-CoV-2, the assess the ability to modify COVID-19 infection, to evaluate viral infectionkinetics, and to evaluate the vaccine induced immune response. This initial efficacy trial will tell us much aboutthe adaptive immune response in persons who receive a SARS-CoV-2 S protein based vaccine and about theirability to modify the disease course of COVID-19. In addition, it will improve our understanding of the dynamicsand duration of these responses and will inform rational design and testing of preventive and therapeuticmonoclonal antibody interventions. Lastly, the results of this trial will be used to assess registration of thisvaccine product as well as to modify future COVID-19 vaccine trials planned over the next 12 months.",2020,2020,Fred Hutchinson Cancer Research Center,1414274,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C06837,3U01CA199240-04S1,The impact of the COVID-19 pandemic on African American cancer survivors and their caregivers,"PROJECT Summary: The Detroit Research on Cancer Survivors (ROCS) cohort focuses on African American lung, breast, prostate,colorectal and endometrial cancer survivors, as well as survivors of any type of cancer diagnosed under age 50,and a subset of their caregivers. This population-based African American cancer cohort will ultimately includeover 5,000 cancer survivors with annual follow-up, supporting a broad research agenda aimed at identifyingmajor factors affecting cancer survivorship in African Americans. The inclusion of a cohort of caregivers allowsfor a more detailed evaluation of social support determinants of outcomes. To date, we have enrolled 3,633African American cancer survivors and 781 caregivers who have completed a baseline survey. ROCSparticipants live in an area of the country being especially hard hit by the COVID-19 pandemic. Both the ROCSsurvivors and caregivers carry one or more characteristics that put them at high risk of COVID-19 infection andpoor outcomes once infected, including African American race, poverty, comorbid conditions, loss of income andexposures associated with work in essential services. The associated shelter-at-home order in Michigan addssubstantial stress by reducing income and limiting social support. It has also altered cancer care in a numbersof circumstances, with some cancer providers delaying treatment and follow-up visits. In this supplement, wepropose the following specific aims: 1) Administer a supplemental COVID-19 questionnaire to ROCS cancersurvivors and their caregivers, and 2) Conduct preliminary analyses of anxiety and depression, financialhardship, barriers to care and quality of life among cancer survivors and their caregivers during the COVID-19outbreak. The Detroit ROCS cohort is the largest African American cancer cohort, including caregivers, set in alarge minority community, being disproportionately impacted by the COVID-19 pandemic. The additional surveywill provide valuable information about the effects of COVID-19 on these important populations during thisunprecedented time.",2020,2021,Wayne State University,153988,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C06838,1R21AI158335-01,Mechanisms and functional implications of SARS-CoV-2 mRNA capping and modification.,"SARS-CoV-2 must cap and methylate its mRNAs to ensure their stability, translatability, and avoiddetection by host innate immune mechanism as non-self transcripts. The process of RNA capping, therefore,is pivotal to the success of a SARS-CoV-2 infection. It also represents a key contributor to the molecularmechanisms of pathogenesis as well as a very attractive target for the development of antiviral therapeutics.However, there are three key knowledge gaps that have slowed progress in our understanding of thisimportant area of coronavirus molecular biology that will be addressed in this proposal. First, the identity of theguanylyltransferase (GTase), the centerpiece of the viral RNA capping machinery that transfers GTP to the 5'end of the nascent transcript, is unknown. We will use a two-pronged strategy of complementary molecularand biochemical approaches to address this glaring gap in our understanding of SARS-CoV-2 mRNA cappingmechanisms, laying the foundation for the development of capping-targeted antivirals. Second, while RNAcapping is a regulated process and uncapped RNAs play an influential role in the biology of other positivesense RNA viral infections, it is not known if RNA capping is a regulated or a default event in coronaviruses.We will determine if uncapped RNAs are produced by SARS-CoV-2 in order to establish the foundation for arole of regulated capping and non-coding viral transcripts in SARS-CoV-2 infections. Finally, every cellularmRNA that begins with a terminal adenosine has that residue 2'O methylated at the ribose ring as well as N6methylated on the adenosine base (m6Am). The strong conservation of this m6Am modification indicates itsimportance in cell biology, an assertation recently confirmed with data suggesting that the modificationincreases translatability and facilitates recognition of the transcript as `self'. Interestingly, SARS-CoV-2 andother coronaviruses all initiate their transcripts with an A residue, but it is not known whether that A residuecontains an m6A modification. In the final part of this project, we will determine the m6A modification status ofthe terminal 5' A residue of SARS-CoV-2 mRNAs and investigate the role that the modification (or lack thereof)plays in the biology of coronaviral transcripts. Collectively these studies will provide important new insights intothe molecular biology of SARS-CoV-2 and open up avenues for the development of broad-spectrum anti-coronaviral therapeutics.",2020,2022,Colorado State University,407060,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06839,3R01ES029963-02S1,The Impact of Air Pollution Exposure on COVID-19 Severity and Mortality,"PROJECT SUMMARY/Abstract: The novel coronavirus disease 2019 (COVID-19) pandemic is currently the most emergent public healthdisaster of the entire world. COVID-19 disproportionately affects older adults, people having history of smokingand comorbidities like diabetes, obesity, and hypertension. There is no vaccine and treatment for COVID-19,therefore, public health interventions have been taken to control disease transmission. Also, searchingmodifiable environmental factors that can help reduce the COVID-19 severity and mortality is crucial. Airpollution exposure has been shown to have a systemic effect on the human body including lung functionimpairment and immune alterations. Recent two ecologic studies from Europe and the United States havesuggested that higher long-term ambient air pollution exposure (PM2.5 and NO2) significantly contributes to theCOVID-19 mortality. These findings from aggregated data of air pollution exposure and total number of deathsin large geographic areas need to be further verified by cohort study with individual data of air pollutionexposure and COVID-19 case progression and mortality. Also, susceptibility factors such as low socialeconomic status (SES), race/ethnicity, smoking exposures and comorbidities need to be accounted for in theanalysis. To address the urgent public health question about the role of air pollution exposure in COVID-19progression, we propose to conduct a retrospective cohort study based on the existing EMR data of all COVID-19 cases (n>7000) diagnosed at Kaiser Permanente Southern California (KPSC) medical centers. Specificaims of this proposal have been expanded from our ongoing NIEHS-supported R01 study investigatingprenatal air pollution exposure and children's autism risk among 440,000 KPSC mother-child pairs (APARstudy, 1R01ES029963). In this proposal, the main outcomes of interest are COVID-19 severity assessed byhospitalization, ICU admission and ventilator use, as well as death. Details dates will be available throughEMR. Natural language processing technologies will be applied to identify the date of first COVID-19 symptomonset for each case. Thereafter, the earliest date among COVID-19 symptom onset and clinical diagnosis willbe used as the study entry date. Then short- and long-term air pollution exposure will be estimated for eachcase by averaging air pollution exposure levels during one-month and one-year before the study entry date.Both ambient (PM2.5, PM10, NO2 and O3) and traffic-related (line dispersion model estimated NOx) air pollutionexposure will be assessed based on individual residential addresses. Detailed residential history of all KPSCmembers have been well-maintained by the KPSC system. Key covariates including age, sex, race/ethnicity,smoking exposure, body mass index, comorbidities, medication use, and meteorological data will be extractedto control for confounding and identify susceptible high risk subgroups. With the unique cohort data resourceand world-renowned epidemiologists and exposure scientists, this one-year study will greatly enhance ourknowledge about the effect of air pollution exposure on COVID-19 progression and death.",2020,2021,Kaiser Foundation Research Institute,670296,Human Populations | Environment,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Post acute and long term health consequences,2020 +C06840,3UM1AI068613-14S1,LC: HIV Prevention Trials Network - Laboratory Support for the SARS-CoV-2 Seroprevalence Study (CoVPN 5002),"PROJECT Summary: This project will provide laboratory support for a large, cross-sectional COVID-19 seroprevalence study that willbe conducted in 23-25 communities in the United States: the SARS-CoV-2 Seroprevalence Study (COVID-19Prevention Trials Network [CoVPN] 5002). The CoVPN 5002 study will include collection of data and specimensfrom up to 98,000 persons, including persons living in nursing homes and assisted living facilities, personsattending clinics, and persons living in study communities. The study will include children (ages 2 months andolder) and adults. Participants will be tested for COVID-19 in real time using SARS-CoV-2 RNA assays.Seroprevalence will be assessed retrospectively using stored specimens from all participants using a sensitiveand specific SARS-CoV-2 IgG assay (Abbott ARCHITECT COVID-19 IgG test). A subset of specimens fromCoVPN 5002 will also be used to evaluate the performance of diagnostic and serologic SARS-CoV-2 assaysusing alternate specimen types (saliva and dried blood spots). Collection of these sample types is simpler andless invasive than collection of nasal swabs or collection of blood samples by phlebotomy. This project will alsouse of specialized assays to evaluate the serologic response to SARS-CoV-2. This will include use of a massivelymultiplexed antibody profiling assay (CoronaScan) to measure antibody binding to SARS-CoV-2 peptidesspanning the viral genome. This analysis will provide information on the fine specificity of the antibody responseto SARS-CoV-2 and reactivity to other coronaviruses and other viruses that cause respiratory illnesses. Thistesting may also identify participants who have false positive or false negative test results using the ARCHITECTCOVID-19 IgG test. Specimens that have antibodies to the SARS-CoV-2 spike protein (identified using theCoronaScan assay) will be further assessed using a phenotypic recombinant viral neutralization assay(PhenoSense Anti-SARS-CoV-2 Neutralizing Antibody Assay). This analysis may identify viral epitopesassociated with viral neutralization and may also identify demographic and clinical factors associated with thepresence of neutralizing antibodies. Specimens from CoVPN 5002 will also be used for further development andevaluation of a novel, massively multiplexed pathogen detection assay, cRASL-Seq, that does not require RNAextraction. Findings from this research will inform the design of clinical trials for SARS-CoV-2 prevention andtreatment by providing information about the seroprevalence of COVID-19 in diverse geographic regions andparticipants groups, including asymptomatic and symptomatic individuals, children and adults in the generalpopulation, and adults at increased risk for COVID-19.",2020,2020,Johns Hopkins University,167145,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06841,3U54HL127366-06S2,Discovering existing medicines that abrogate cellular responses to SARS CoV-2 infection,"PROJECT SUMMARYOur overall strategy is to screen existing drugs for their unexpected ability to abrogate key aspects of SARS-CoV-2 infection. The proposal will leverage the infrastructure we have created as part of the LINCS Consortiumto use gene expression profiling to discover existing drugs that either block the cellular mechanisms required forviral infection, or block the cellular response to infection that causes disease. While there is much biologicallearning to be done, the focus of this proposal is not basic biology, but rather on the discovery of drugs that couldbe rapidly tested in patients. For this reason, we emphasize existing drugs (those that are either FDA-approved,EMA-approved, or are in clinical development) because of the pace at which they can be advanced to clinicaltrials. Our proposed approach leverages capabilities developed under our Common Fund-supported LINCSCenter for Transcriptomics. First, we have created a ""shovel-ready"" production-scale data generation capabilitythat can now be brought to bear on COVID-19. Second, we have assembled a drug repurposing library with~10,000 drugs that are either FDA-approved or are in clinical development. Third, through our LINCS experience,we have learned that real power comes from unleashing the world's scientific community by creating publicresources that can be utilized by others. In this project, we will screen ~10,000 drugs in lung epithelial cells andmonocytic immune cells, using gene expression profiling as the readout. We will make this Drug RepurposingLINCS dataset immediately publicly available, so that anyone in the research community can query it withrelevant signatures -- including those that have yet to be discovered. High priority drugs identified throughanalysis of these data will be subjected to orthogonal tests of antiviral and immune function. An important aspectof this proposal will be the creation of a COVID-19 Drug Repurposing Portal which will house all of the raw andprocessed data generated by this proposal, together with biologist-friendly analytical and visualization tools thatwill enable the entire COVID-19 research community to identify top priority drugs for pre-clinical and eventuallyclinical testing as anti-COVID-19 therapies.",2020,2021,Broad Institute Inc,1652790,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C06842,3U54CA199090-06S1,Repurposing of cancer therapeutics for treatment of patients with COVID-19 disease,"Project Summary: The pandemic COVID-19 has, as of April 13, 2020, infected nearly 2M individuals worldwide, with over560,000 U.S. cases and over 22,000 U.S. deaths. There are no FDA approved vaccines or treatmentsfor COVID-19. This supplemental proposal describes the accelerated development of such a drug,with potential near-term uses of these early therapeutic candidates for probing the structural-functionrelationships between the SARS-CoV-2 spike protein and the human ACE2 receptor protein. This workbuilds directly from Project 2 of the NCI-supported U54 NSBCC program. The specific aims of thatproject center around the technology of Protein Catalyzed Capture agents (PCCs),1 with a specificfocus on developing technologies for the high-through production of PCCs, as well as an emphasis ondrug-targeting the KRASG12D oncoprotein. A unique aspect of PCCs is that they are, by design,developed to bind to a specific epitope on a specific protein,2 thus providing an avenue for targeting anepitope containing a genetic mutation (relevant to oncoproteins),3 or providing an avenue for targetingepitopes that are broadly conserved, which bears relevance to targeting strategies aimed at the SARS-CoV-2 coronavirus. That NSBCC-funded project has proceeded well (with progress towardsKRASG12D-specific inhibitors recently attracting additional investments). Further, we have also recentlyshown, using other funding, that the platform can be harnessed to selectively target antibiotic resistancepathogens using a variant of the PCC technology termed antibody-recruiting(AR) PCCs.4 Here weseek to combine the high-throughput aspect of PCC development that has been supported by the NCI,5with the pathogen-targeting approach, to develop a series of precisely targeted inhibitors againstSARS-CoV-2. This work has already been moving forward for the past few weeks, and is nearing thepoint where animal model work will soon be required.",2020,2021,Institute For Systems Biology,183000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06843,3UL1TR002649-03S3,N3C & All of Us Research Program Collaborative Project,"Project Summary/Abstract: The COVID-19 pandemic presents unprecedented clinical and public health challenges. Though institutionscollect large amounts of clinical data about COVID-19 cases, these datasets individually might not be diverseenough to draw population level conclusions. Also, statistical, machine learning, and causal analyses are mostsuccessful with large-scale data beyond what is available in any given organization. To tackle this problem,NCATS introduced the National COVID Cohort Collaborative (N3C), an open science, community-based initiativeto share patient level data for analysis. The initiative requires participating institutions to share information abouttheir COVID-19 patients in a standard-driven way, including demographics, vital signs, diagnoses, laboratoryresults, medications, and other treatments. The data from multiple institutions will be merged and consolidated,and access will be provided to investigators through a centralized analytical platform. The COVID-19 datasharing collaboration with the N3C initiative offers a mechanism to initiate collaborations with other NIHsponsored data sharing programs, such as the All of Us Research Program (AoURP).This administrative supplement will support efforts to clean and standardize data at VCU, and to transferit to the N3C data repository. The supplement will also assist in introducing new services at the WrightCenter to support our investigators to use the N3C resources. It will also enable collaboration with theAoURP by establishing a pipeline to collect and transmit consented patients' EHR data and by buildingon existing community outreach pathways to recruit additional participants for the AoURP. The projectwill be overseen by the PI/Executive Committee and supervised by the Director of Research Informatics.Procedures and services developed at our local CTSA hub will be shared and disseminated to the CTSAnetwork.",2020,2023,Virginia Commonwealth University,346608,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2020 +C06844,3UM1AI148574-01S1,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT Abstract: This supplement proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN)research to be carried out at the NYU VTEU. We will participate in the implementation of a COVID-19 vaccineefficacy trial ""A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults toDetermine the Safety, Efficacy, and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine,for the Prevention of COVID-19."" In addition to the above, and as a supplement request to further address themission of the CoVPN, we are requesting funds for other CoVPN studies ""and other COVID-related research"".We plan to conduct an additional study within the CoVPN - Monoclonal Antibody (mAb) Studies: A Phase 3,Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of IndividualsInfected with SARS-CoV-2.With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 inSARS-CoV-2 infected individuals. The vaccine trial we will conduct is a phase 3, placebo-controlled, double-blinded study will test the efficacy of AZD1222, a recombinant replication-defective chimpanzee adenovirusexpressing the SARS-CoV-2 spike (S) surface glycoprotein, to modify COVID-19 disease in adults 18 year ofage and older. Participants will be recruited from up to 100 clinical trial sites across the US, using dataanalytics to target high risk individuals with a diverse racial and ethnic profile.The MAB study we will conduct is a pivotal phase 3 randomized, double-blind, placebo-controlled study inadults with household contact exposure to individuals with SARS-CoV-2 infection in geographic areas with anactive COVID-19 outbreak. An ideal agent for prophylaxis should be fast acting and highly effective and shouldprotect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two differentmonoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike (S) protein that bind toand facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combinationagainst SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease orreduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptomsand adverse outcomes following infection.We also request site preparedness funds, and fund for Dr Mulligan's role as national PI of an additional MABstudy (Lilly MAB in nursing home residents and staff, for COVID-19 prevention).",2020,2022,New York University School Of Medicine,9214781,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Phase 3 clinical trial | Prophylactic use of treatments | Phase 3 clinical trial,2020 +C06845,3P51OD011133-22S3,Significant expansion of the SNPRC ABSL3 capability in the wake of COVID-19,"Research Summary/Abstract.The SNPRC is one of seven NIH supported National Primate Research Centers. The center receivesadditional support from the sponsor organization, Texas Biomedical Research Institute. The center andthe institute have a very strong focus on biomedical research involving infectious disease. The siteoperates primate studies at ASBL 2-3-4 levels. Prior to March 2020, the SNPRC supported studies inNHPs on TB, and TB/HIV co-infection in its new ABSL3 lab (Bldg 12) which can house ~80 rhesusmacaques.In response to the global pandemic caused by the novel coronavirus, SARS-CoV-2; Texas Biomed andthe SNPRC have become interested in developing NHP models of this infection, and the ensuingdiseases, COVID-19. This has led to very early SARS-CoV2 infection studies for model development,in three species of research NHPs (https://www.biorxiv.org/content/10.1101/2020.06.05.136481v1).We are currently supporting a number of NHP studies for Fortune 500/leading biotechnologycompanies for preventative vaccine and therapeutic candidates for SARS-CoV-2/COVID-19. Ourcurrent ABSL3 newly opened in Q4, 2019 is capable of housing up to 80 macaques, across four rooms.This facility is currently in use at virtually full capacity due to COVID-19 and TB work. Due to the urgentnature for research to address SARS-CoV-2, as well as to support research in any future emergingpathogens, the center must therefore expand its ABSL3 primate capabilities. The historic (now closed)ABSL3 located in Bldg 23 on campus can be renovated to a state of the art ABSL3 space. Renovationof this space would bring online four more rooms in ABSL3 containment; with the capacity of anadditional 64 macaques. This would represent a significant, 80% increase in the number of macaquesthat could be enrolled on SARS-CoV2 studies; and a gain of four additional individual study rooms. Inthe short-term this supplemental funding would allow us to complete the COVID-19 vaccinationexperiments currently being supported by the SNPRC. Long-term we would be prepared to respond toCOVID-19 vaccine and therapeutic testing work that is expected to be performed by the NPRCs insupport of ACTIV and Warp Speed operations, as well as any other ABSL-3 work.",2020,2021,Texas Biomedical Research Institute,2000000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,1999 +C06846,3R01AI147394-01A1S1,COVID-19 competitive revision: BALANCING PROTECTIVE IMMUNITY AND CHRONIC SEQUELAE BY RESIDENT CD8 T CELLS,"Summary/AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an international outbreak of respiratory illness termed COVID-19. The primary determinant of outcome in COVID-19 infection is age, with the vast majority of morbidity and mortality occurring in the elderly. Current and emerging data suggests that survivors of severe COVID-19 infection will likely develop pulmonary fibrosis and persistent impairment of lung function. Given the potential catastrophic spreading of SARS-CoV-2 infection, it is predicted here that there will be a large number of individuals that recover from severe COVID-19 infection and develop permanent impairment in lung function due to lung fibrosis. However, there are no preventive means nor therapeutic interventions available to slow down and/or reverse lung fibrosis development following any viral pneumonia. We hypothesize that aged survivors of severe COVID-19 infection will develop persistent impairment of lung function due to pulmonary fibrosis even after complete resolution of acute infection. Furthermore, we hypothesize that recovered patients will pulmonary fibrosis will exhibit enhanced CD8 TRM cell presence in their respiratory tract and/or enhanced CD38 expression on CD8 TRM cells, contributing to tissue fibrosis and impaired lung function. To test these hypotheses, we have proposed two specific Aims in this study. Specific Aim 1: To determine respiratory CD8 TRM cell levels and quantitative lung fibrosis scores following severe SARS-CoV2 infection. Aim 2: To determine whether targeting CD8 TRM cells and/or CD38 pathway will attenuate post-viral pulmonary fibrosis and preserve lung function in elderly survivors of severe viral pneumonia. If successful, we expect that this study will establish an important role for CD8 TRM cells in lung fibrosis following COVID-19 pneumonia. Furthermore, this study will generate the necessary pre-clinical data to design early phase clinical trials using a new CD38 Ab that specific blocks CD38 ectoenzyme function as a novel therapy for recovered COVID-19 patients with lung fibrosis.",2020,2023,Mayo Clinic Rochester,211560,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C06847,3R01AI057555-17S1,Molecular mechanisms underlying immunosuppression and inflammation caused by SARS-CoV2 proteins,"PROJECT SUMMARY/Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) causes coronavirus disease2019 (COVID-19), which is characterized by acute inflammation in the lung and other organs, such as theheart and intestine. It is increasingly clear that the pathogenesis of SARS-CoV2 involves suppression ofantiviral innate immunity and induction of inflammatory responses. SARS-CoV2 suppresses induction of theantiviral type I interferons (IFNs) and, thereby, escapes from destruction by the early phase antiviral immunity.Subsequent induction of inflammatory responses drives the development of COVID-19. Understanding howSARS-CoV2 suppresses type I IFN expression and induces inflammatory responses, is crucial for designingtherapeutic approaches. Based on the studies of SARS-CoV, the close homolog of SARS-CoV2, several viralproteins have been implicated in the interplay with host immune system, contributing to the suppression of typeI IFN responses and induction of proinflammatory cytokines. The major goal of this supplementary applicationis to understand the mechanisms by which SARS-CoV2 proteins suppress antiviral innate immunity andstimulate exacerbated inflammatory responses. We will perform two specific aims. In Specific Aim 1, we will examine how SARS-CoV2 proteins suppress TBK1 signaling and antiviral innateimmunity. As described in the parent grant, TBK1 is a kinase that responds to signals from the toll-likereceptors (TLRs) and other pattern-recognition receptors (PRRs) during viral infections and mediates inductiontype I IFNs. At the same time, TBK1 negatively regulates proinflammatory cytokine induction to preventexacerbated inflammation. Our parental grant focuses on the elucidation of how TBK1 regulates TLR signalingand intestinal inflammation caused by gut microbes. In this supplementary application, we will specificallyaddress how SARS-CoV2 proteins modulate TBK1 signaling in the suppression of antiviral immunity andstimulation of inflammation. We will examine our hypothesis that suppression of TBK1 signaling by SARS-CoV2 proteins not only inhibits type I IFN production but also promotes inflammatory responses. In Specific Aim 2, we will systematically define the mechanisms by which SARS-COV2 proteins induceinflammatory responses using both cell culture and mouse models. We will examine the signaling pathwaysinvolved in SARS-CoV2-induced expression of proinflammatory cytokines in macrophages and epithelial cells.We will also examine how the Spike protein of SARS-CoV2 downregulates its cellular receptor, angiotensin-converting enzyme 2 (ACE2). Since ACE2 is a pivotal anti-inflammatory factor, we hypothesize that Spikeprotein-induced ACE2 downregulation critically contributes to the induction of lung and intestinal inflammation.We believe that these proposed studies address novel mechanisms that mediate the pathogenesis ofCOVID19 and will have important implications for COVID19 therapies.",2020,2023,The University of Texas MD Anderson Cancer Center,162946,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C06848,3U54CA163004-09S1,"SARS-CoV-2, ACE2 and Esophageal Neoplasia","The SARS-CoV-2 pandemic has led to massive morbidity and mortality worldwide due to COVID-19, with the United States particularly affected. Risk factors for COVID-19 include male sex, older age, and obesity, amongst others, which are also key risk factors for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Thus, patients with BE will likely be infected with SARS-CoV-2 at markedly higher rates compared to the general population. Thus, patients with BE will likely be infected with SARS-CoV-2 at markedly higher rates compared to the general population. SARS-CoV-2 infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor and subsequent viral spike protein cleaving by transmembrane serine protease 2 (TMPRSS2). Infection induces key pathways and downstream effectors, resulting in pronounced inflammation. ACE2 is highly expressed in esophageal tissue, ACE inhibitors reduce NF-κB protein expression in BE, and ACE inhibitor use is associated with reduced risk of EAC. It is therefore plausible that SARS-CoV-2 infection in BE patients can result in direct effects on BE tissues that accelerate neoplasia. We published a retrospective cohort study of >1,600 hospitalized COVID-19 patients and found that use of the histamine-2 receptor antagonist famotidine was associated with a >2-fold reduction in the risk of death. While potential mechanisms underlying this observation remain poorly understood, famotidine may not only improve short-term clinical outcomes in these patients but also ameliorate the pro-neoplastic effects of SARS-CoV-2 in BE. Proton pump inhibitors (PPIs) were associated with worse outcomes in the cohort study, and we previously showed that PPI administration leads to increases in the renin-angiotensin pathway in the gut microbiome. Thus, we hypothesize the following: 1) BE patients with a history of COVID-19 are at increased risk for progression to EAC; and 2) famotidine may be indicated instead of PPIs for BE patients with a documented history of COVID19. In this proposal we will address the following specific aims: Aim 1) To define the functional role of ACE2 and TMPRSS2 in BE and EAC cells; Aim 2) To determine whether famotidine influences SARS-CoV-2 infection in BE and EAC cells; Aim 3) To assess the relationship between TMPRSS2 and ACE2 expression and immune cell populations in BE. A history of COVID-19 may represent a novel marker for risk for progression to EAC among BE patients, and this may need to be incorporated into clinical profiles aimed at identifying appropriate high-risk patients for screening and surveillance. Furthermore, treatment with famotidine and not PPIs may be more appropriate for BE patients with mild reflux symptoms and a history of documented COVID-19.",2020,2022,Columbia University Health Sciences,162000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Supportive care, processes of care and management",2011 +C06849,1R21ES032767-01,"Investigating linkages between arsenic exposure, diabetes, and COVID-19 infections and risks on the Navajo Nation","Project Summary: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has generated fear anduncertainty as COVID-19 cases and fatalities spread across the globe. COVID-19 infection rates on tribal landsare more than four times the US national average and are still increasing. In the US, the highest COVID-19infection rate per capita is on the Navajo Nation, the second largest federally recognized tribe. COVID-19cases and deaths for the Navajo Nation continue to rise as COVID-19 cases have begun to decline in some ofthe initially hardest hit states. There are many reasons that Diné people (Navajo) are at higher risk for COVID-19 infections, complications, and death including, but not limited to food, energy and water-insecurities, highprevalence of underlying medical conditions (comorbidities), and environmental health factors. However, we donot have direct evidence that the lack of access to healthy foods, high prevalence of diabetes, and heavymetal-contaminated water are responsible for increased COVID-19 infections on the Navajo Nation. There isan urgent need to identify the environmental and individual risk factors associated with COVID-19 infectionrates and deaths among Navajo Nation residents to inform new strategies and policies to mitigate the currentspread of COVID-19 and prevent future outbreaks. Our long-term goal is to mitigate the spread of COVID-19and other outbreaks on the Navajo Nation. Our research objective is to identify individual and environmentalrisk factors for COVID-19 infection and death among Navajo Nation residents. We hypothesize that individualswith comorbidities (e.g., diabetes), in low socioeconomic situations (e.g., households without indoor plumbing),and/or living with access to water sources with inorganic contaminants will have a higher risk of COVID-19infection and death. The rationale for the proposed research is that, once the specific risk factors for COVID-19infection and death are known on the Navajo Nation, it will be possible to develop useful community educationstrategies, public health messaging and interventions that may benefit these high-risk communities. AIM 1:Identify environmental and individual risk factors for COVID-19 infection and death by Chapter (regions) on theNavajo Nation within 6 months. AIM 2: Identify community education mechanisms, public health messagingand interventions to mitigate risk factors for COVID-19 infection and death in Navajo Nation. AIM 3:Determine effectiveness of community education and public health messaging on knowledge of public healthpractices (e.g. water sources, distribution) to prevent COVID-19 infection and death among Navajo Nationresidents. The Navajo Nation is actively addressing COVID-19, the Navajo Nation needs access to data-drivenanalyses for decision-making. We have chosen to focus on secondary data for the initial project activities formultiple reasons.",2020,2022,University Of Arizona,198521,Human Populations,Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Community engagement | Communication | Individual level capacity strengthening,2020 +C06850,3R01CA207189-05S1,Regulation of Nutrient Stress-Induced Macropinocytosis in Pancreatic Ductal Adenocarcinoma,"PROJECT Summary: The world has been shocked by the recent COVID-19 pandemic. Macropinocytosis is a form of endocytosis thatviruses use to gain entry into cells or to facilitate infection. Our laboratory has the most extensive experience ininvestigating macropinocytosis in the context of cancer, where it functions as a nutrient acquisition pathway2-12.Macropinocytosis is unique among other endocytic pathways because it is preceded by plasma membraneactivity in the form of ruffling. When ruffles fuse with each other they form a macropinosome that encapsulatesthe surrounding fluid and associated particles. Viruses can use macropinocytosis for cellular internalization orthey can hijack macropinocytosis for other aspects of infection. Severe acute respiratory syndromecoronaviruses (SARS-CoVs) induce macropinocytosis late in infection that is continuous, independent from cellentry, and associated with increased infection in vitro. These viruses use their Spike protein to signal throughthe epidermal growth factor receptor (EGFR) to stimulate macropinocytosis, and inhibitors of macropinocytosisor EGFR lead to a reduction in viral spread. While CoVs do not seem to utilize macropinocytosis for entry intothe cell, they do use later steps in the macropinosome maturation pathway to augment infection. The maturationof the macropinosome is not very well characterized, but there are some indications that specific signalingpathways are involved. We have extensively studied EGFR-driven macropinocytosis in cancer cells and we canuse this expertise to determine strategies for blocking macropinosome maturation and SARS-CoV-2 infection.Our hypothesis is that SARS-CoV-2 uses mature macropinosomes as a way to spread to surrounding cells,either by inducing `macropinosome bursting' as occurs in a process called methuosis, or by travelingextracellularly via recycling macropinosomes. In this proposal, we will explore this hypothesis by 1) taking acandidate approache to blocking macropinosome maturation and 2) determine the mechanism of SARS-CoV-2viral escape that involves macropinocytosis. This project will be of great significance and impact because, byand large, a detailed picture of what controls macropinosome maturation in the context of EGFR signaling andSARS-CoV-2 is lacking. Moreover, it will constitute the first evaluation of the impact that candidate inhibitorshave on macropinosome maturation. Understanding the regulators of macropinosome maturation will shed lighton a critical aspect of CoV biology and could lead to new approaches for the treatment of COVID-19.",2020,2021,Sanford Burnham Prebys Medical Discovery Institute,195000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2016 +C06851,3UM1AI148450-01S2,CoVPN - COVID Countermeasures,"The Vaccine and Treatment Evaluation Units (VTEUs) are a critical resource for the NIAID Infectious DiseasesClinical Research Consortium to conduct clinical research and trials to evaluate vaccines, preventive biologics,therapeutics, diagnostics, predictive markers, and devices for the treatment and prevention of infectiousdiseases in people of all ages and risk categories. The VTEU network sites must flexible and respond toemerging threats and changing NIAID priorities. To this end, the University of Rochester VTEU (UR VTEU) willcollaborate with NIAID and the VTEU leadership group (VTEU LG) to address and prioritize initiatives forinfectious diseases such as respiratory, enteric, sexually transmitted infections and antibiotic resistantorganisms as well as maintain flexibility to switch focus to emerging threats as the need arises. The Universityof Rochester is fortunate to enjoy a community with a very positive attitude towards clinical research andcollaborative relationships between the major healthcare providers in the city providing access to all thehospitals, clinics and practices in the area. The UR VTEU offers a very experienced administrative and clinicalgroup with a proven track record of successful multicenter clinical trial work. With the support of the VTEU LG,the UR VTEU will be well positioned to develop as well as implement concepts and projects that addressimportant NIAID priorities and formulate best practices, efficiencies and standard operating procedures amongVTEU sites. UR VTEU investigators have expertise in adult and pediatric clinical research as well asrecruitment of vulnerable populations into clinical trials and thus can anticipate successful recruitment of youngand older adults, infants, young children and adolescents, and pregnant women. Additionally, the closerelationship of the Monroe County Health Department with the University provides access to patients withsexually transmitted diseases for study participation. We will provide capacity to perform phase 1-3 clinicaltrials and pharmacokinetic studies as well as surge capacity in terms of personnel and clinical research sites torapidly respond to urgent NIAID demands. Importantly, our investigators have experience conducting challengeand isolation studies and can provide VTEU facilities for such projects. Our research laboratory expertise willprovide the VTEU network with a variety of state of the art technologies to interrogate the host response toinfection and immunization as well as develop a deeper understanding of pathogenesis for many infectiousdiseases. Specifically, core faculty have expertise in a wide range of novel immunologic assays as well astranscriptional and microbiome analysis. In addition, the UR VTEU will provide research opportunities andeducation for junior faculty to train the next generation of physician scientists. All clinical trials will adhere toNIAID/NIH requirements and comply with Good Clinical Practice. In summary, the UR VTEU site will offer anenthusiastic and diverse group of investigators with a track record of participating in collaborative research andthe necessary scientific, clinical, administrative and organizational structure to support NIAID activities.",2020,2022,University Of Rochester,5088428,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2020 +C06852,3R01AI123126-05S1,Innate immune responses to SARS-CoV-2 in the lung and blood of patients with severe COVID-19,"SUMMARYCOVID-19 disease is an ongoing global pandemic caused by a new beta-coronavirus SARS-CoV-2. A major obstacle to battling SARS-CoV-2 is a better understanding of the human innate immuneresponses that can lead to an uncontrolled hyper-inflammation in the lung and, ultimately, to anacute respiratory distress syndrome (ARDS) in some patients but not others. Due to the rapidemergence of this pandemic, very limited knowledge is available on the lung-specific innateimmune responses to SARS-CoV-2 that could lead to ARDS (and in some cases death) or insteadelicit a protective antiviral response (e.g., type-I interferons, interferon-stimulated genes).The role of the human innate immune system, particularly the myeloid cells, in initiating a ""cytokinestorm"" and generalized hyper-inflammation has been reported, but specifically how lung-residentmacrophages vs. infiltrating monocytes differentially respond to SARS-CoV-2 and how eachmyeloid subset contribute to either protective antiviral responses or uncontrolled hyper-inflammation and ARDS remain unknown. Hence, an in-depth study of the myeloid compartmentin the lung and blood of severe COVID-19 patients in ICU is critical to better understand theinitiation and persistence of ARDS and, most importantly, to the development of more efficientand targeted therapy.Our project's primary objective is to resolve, at a single-cell level, the specific myeloid subsets,including lung-resident alveolar and interstitial macrophages, dendritic cells, as well as infiltratingblood monocytes, that are responsible for protective antiviral responses (e.g., type-I interferons,interferon-stimulated genes) and/or aberrant hyper-inflammatory responses that lead to ARDS(e.g., ""cytokine storm"", neutrophil recruitment, etc.). Through these studies, we will develop novelinsights into the molecular programming and heterogeneity of the human innate immuneresponses to SARS-CoV-2 infection and identify potential target genes to inform effectivetreatment strategies.",2020,2021,Emory University,359677,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C06853,3R01DK121140-01A1S1,Alternative complement pathway regulation of beta cell homeostasis,"Project Summary/Abstract: Coronavirus disease of 2019 (COVID-19) is a worldwide pandemic that quickly grew fromthe end of 2019 to more than 5.6 million confirmed cases as of late May 2020. The numberof cases is approaching 1.7 million with over 100,000 deaths in our country. Within theUnited States, there is tremendous regional variability in the prevalence of COVID-19 withNew York State and specifically the New York City metro area being particularly hard hit.The demographic risk factors for adverse outcomes such as need for mechanicalventilation and mortality in COVID-19 include diabetes and obesity. Hyperglycemia inCOVID-19 is associated with poor outcomes; however, the mechanism for hyperglycemiaremains unknown. Emerging evidence show that SARS-CoV-2 could infect cells outsideof the nasopharynx and lungs. ACE2 is a coreceptor for SARS-CoV-2 and is expressedon pancreatic islet cells, including beta cells. We hypothesize that SARS-CoV-2 directlyinfects beta cells to cause beta cell dysfunction and acute hyperglycemia. We propose todefine the physiological mechanism of hyperglycemia in COVID-19 patients assessingsamples from a large biobank. Understanding the mechanism for hyperglycemia maytranslate into clinical treatments that may improve care of COVID-19 patients.",2020,2023,Weill Cornell Medicine - Cornell University,372799,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06854,3P30CA125123-14S1,Defining Pathologic Immune Dysregulation in 2019-CoV: Opportunities for Risk Stratification and Therapeutic Immune Modulation,"COVID-19 is a coronavirus similar to SARS and MERS. Clinical features among critically ill patients infected with these new viruses includes features of pathologic inflammation, and increased inflammation in patients infected with COVID19 (elevated ferritin, elevated IL6, elevated d-dimer) has been associated with risk of death.1 For some patients, corticosteroids or other immune suppression may be detrimental.2 However, for others, control of extreme inflammation may be life-saving. This concept is illustrated by re-analysis of data from a phase 3 randomized study of IL-1 blockade with anakinra in patients with severe sepsis. Analyzed as a group, anakinra did not confer any benefit. However, in patients with hyperinflammation, there was a significant survival advantage.3 Similarly, cytokine profiling predicts risk of pathologic in inflammation with cancer immunotherapy, and tocilizumab (targets IL-6) and other agents that target cytokines show benefit in patients who develop cytokine release syndrome.4;5 Hemophagocytic lymphohistiocytosis (HLH) is a condition of extreme inflammation that may be caused by inherited defects in cytotoxicity that is fatal without immune suppression. In a mouse model of HLH, blocking IFN specifically improved survival where blocking other pro-inflammatory cytokines did not.6 Emapalumab (IFN antibody) has recently been approved for primary HLH based on results of a single arm trial.7 Our group has evaluated pre-therapy plasma in children with HLH and severe sepsis using unbiased analysis of >130 cytokines and found an IFN signature was specific to HLH and IL-6 to sepsis/SIRS (Figure 1). We hypothesize that analysis of cytokine prolife and immune function in patients infected with COVID19 may identify patients at risk of morbidity and mortality due to pathologic inflammation. Further, these analyses may identify pathways (e.g. IFN) that may be useful to prioritize therapeutic strategies that modulate inflammation. Team Organization: We have assembled an interdisciplinary team of scientific and clinical collaborators (Texas Medical Center: St. Luke's/Baylor College of Medicine, Houston Methodist Hospital, Ben Taub Community Hospital, Texas Children's Hospital; University of Cincinnati, Cincinnati Children's Hospital; and Mt. Sinai School of Medicine) that will provide access to tissue specimens, clinical data and expertise required to efficiency and comprehensively test the role of pathologic inflammation in clinical outcomes of children and adults infected with COVID19. In addition to gaining access to blood and clinical data from hospitalized patients, we will enroll patients with a spectrum of ages and clinical severity in prospective studies/registries which will allow analysis of changes in biomarkers and immune function over time.",2020,2025,Baylor College Of Medicine,400938,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2007 +C06855,3U54AI117804-07S1,Consortium of Eosinophilic Gastrointestinal Disease Researchers,"Project Summary/Abstract: This Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) study will enroll approximately 150families to assess how SARS-COV-2 differentially affects children with Eosinophilic GastrointestinalDisorders (EGIDs) compared to children without these disorders. The proposed work is part of the largerHuman Epidemiology and Response to SARS-CoV-2 (HEROS) study that allows a comparison betweenchildren with atopic conditions and children without those conditions. Although asthma has not beenidentified as a clear risk factor for severe COVID-19 disease, there is evidence that children with asthmaand other atopic conditions have increased susceptibility to viral respiratory infections (Esquivel etal, AJRCCM, PMC5649984) and that viral respiratory infections may result in worsening of underlyingairway disease (Jartti et al, J Allergy Clin Immunol, PMID 28987219). No data currently exist as towhether this is true for SARS-CoV-2 infection or whether allergic airway disease could beprotective. Enrolled families will participate for 6 months completing surveys and biological samplecollections. These children and their families are already enrolled in the CEGIR NIH funded studies andtherefore will overcome many challenges for clinical study implementation. This proposed workremains in scope to the parent award and is responsive to the NOT-AI-20-031.",2020,2021,Cincinnati Childrens Hosp Med Ctr,138242,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C06856,1S10AI160636-01,Personal Protective Equipment for Resources for COVID-19 Related Vaccine and Treatment Clinical Trials and Clinical Studies,"Project Summary/Abstract: Planned COVID-19 vaccine trials require screening, enrolling, and following over 150,000 volunteer studyparticipants over 24 months. The trial participants will be selected based on their risk of COVID-19 infection,with trial participants coming from settings with high rates of community transmission, groups with higher risk ofprogression to symptomatic disease, or both. Study staff working on COVID-19 vaccine trials will need tointeract with trial participants during regular visits as well as conducting in-person assessments of all vaccinetrial participants with symptoms that could be due to COVID-19 disease. This will result in close contactbetween study staff and high-risk participants or infected participants. As a result, study staff need to access aregular supply of personal protective equipment (PPE), including surgical masks, face shields or goggles,gowns, and disposable gloves, as well as the ability to sanitize hands frequently. This combination of PPE willbe used during all risky interactions with study participants, such as during nasal swab collection and duringevaluation of participants for possible study endpoints, including symptomatic COVID-19 disease. In addition,all staff will need to wear surgical face masks during and throughout their normal workday in the health caresetting or on site for mobile study satellite sites. Without appropriate PPE, health care workers are vulnerableto infection with COVID-19, as well as passively transmitting to persons with whom they are in close physicalcontact. Access to adequate PPE is a critical component of the safe and effective conduct of COVID-19vaccine trials, and will enable accurate determination of the study endpoints, especially symptomatic COVID-19 disease.",2020,2021,Fred Hutchinson Cancer Research Center,24903100,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +C06857,3RF1AG059686-01S1,Action of SARS CoV2 in Human Brain Cultures,"PROJECT Summary: There is emerging evidence that SARS-CoV2 or COVID19 gains entry into human brain cells leading to asequela of neurologic symptoms. There is concern that SARS-CoV2 may lead to neurotoxicity and thatneuronal death in the regions of the brain that control respiration and cardiac function may be a contributingfactor to the acute loss of cardio respiratory function and death. SARS-CoV2 could gain access to the brain byseveral routes including through the nose, or neurons innervating infected lung tissue or through the cells liningblood capillaries in the brain. COVID-19 patients lose their sense of smell or taste often before the onset ofrespiratory symptoms and a patient presented with Guillain-Barré syndrome before testing positive for SARS-CoV2. It appears that at least 36% of COVID19 patients had neurologic manifestations including headache,nausea, loss of consciousness, strokes, confusion, encephalitis, meningitis and seizures. These clinicalobservations strongly indicate a role for SARS-CoV2 in the death of neurons and importantly the brain may beone of the first tissues infected and affected. The actions of SARS-CoV2 on the different cells in the brain, aswell as the infectivity, tropism, and replication in brain cells is not yet known. In this application we propose toevaluate: (1) The tropism and replication of SARS-CoV2 in human microglia, astrocytes, neurons, anddetermine relative susceptibility? (2) The mechanisms of cellular injury and evaluate potential protectiveapproaches. (3) Determine the transcriptional responses to SARS CoV2 infection in human neurons,astrocytes, and microglia at the single cell level to gain new insight into the differential response of brain cellsto SARS CoV2 to better understand the neural deficits the virus causes.",2020,2023,Johns Hopkins University,542592,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2018 +C06858,3U34AA026219-03S2,Optimizing PrEP Utilization among Alcohol and Other Drug (AOD) Using Women of Color,"Project Summary: This administrative supplement (PA-18-591) in response to NOT-AA-20-011, leverages an existing NIAAA U34study for time-sensitive research on the impact of social environmental stressors related to COVID-19 on patientand provider experience in the HIV continuum of care for the most HIV-affected ethnic minority femalepopulations in S. Florida, now in one of the epicenters of the new pandemic. The public health emergency posedby COVID-19 has caused unprecedented disruption in daily living, social structures, and employment asmitigation mandates of social distancing have been enforced to slow the spread of illness. Emerging evidencesuggests that the most severe consequences from the novel coronavirus and the mitigation efforts will fall uponU.S. ethnic minority populations historically burdened by health disparities. The parent study, ""Optimizing PrEPUtilization among Alcohol and Other Drug (AOD) Using Women of Color"" (U34AA026219), is the first such projectdevoted to improving implementation and uptake of PrEP among African American, LatinX and Haitian womenin the HIV hotspots of S. Florida and has produced a replicable model driven by community-based participatoryresearch (CBPR). Before COVID-19, these study populations had limited economic resources, prevalent healthdisparities and reported high levels of intimate partner violence. The possible deleterious effects of the pandemichave not yet been investigated or reported for women of color in the South or for the HIV health care providersthat serve them. The supplement will utilize longitudinal, mixed methods data collection within the parent study'ssocial ecological framework to fill critical knowledge gaps about the pandemic's impact on engagement in careand adherence to PrEP and supportive services for alcohol and drug use, mental health, and other ancillary carein the three key ethnic minority populations of women. Our specific aims include: 1) remotely assess experiencesin AOD use, engagement in care, PrEP medication adherence, and HIV risk factors among a sample of womenof color at risk for HIV who are currently enrolled participants in the parent study, comparing measures takenpre-COVID-19, (T1), to post-COVID assessments, (T2 and T3), taken 3 months apart; 2) measure via internetsurveys changes in health services delivery and social distancing due to the pandemic on access to andperceived quality of care, patient trust, and provider stress among a group of health care workers whoparticipated in the community mobilization phase of the parent study; and 3) remotely conduct semi-structuredinterviews with a subset of women from Aim 1 and health providers from Aim 2 to explore COVID-relatedexperiences, needs, areas for improvement in care, and strategies to engage and retain AOD-using women inthe HIV continuum of care. The methods and implementation of the proposed aims will be fulfilled within theparent study's CBPR framework and will inform efforts to offset the adverse stressors of the pandemic andpreserve gains that have been made in HIV prevention in these populations.",2020,2021,Florida International University,147500,Human Populations,Black | Other | Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C06860,3UL1TR003098-02S2,Data Disparities Supplement to Johns Hopkins Institute for Clinical and Translational Research,"The SARS-CoV-2 coronavirus, which causes a respiratory illness known as Coronavirus Disease 2019(COVID-19), has caused a global pandemic of unprecedented proportion. As of April 28, 2020, there were over3 million confirmed COVID-19 cases worldwide, including over 1 million cases within the United States. Inaddition, there has been over 213,000 COVID-19 related deaths globally, including 57,000 deaths in the UnitedStates. The COVID-19 pandemic is disproportionately impacting racial/ethnic minority communities, as well asthose who face socioeconomic disadvantage. Reasons for this disproportionate impact among racial/ethnicminorities include a greater burden of the chronic health conditions that place persons at risk of severe diseaseand death from COVID-19, poorer access to primary and specialty care, an increased risk of contractingCOVID-19 due to barriers to practicing social distancing behaviors, and shortages of testing resources indisadvantaged communities. This pandemic has presented unprecedented needs for timely access to health-related data. The State of Maryland and surrounding regions including the District of Columbia are fortunate tohave a well-functioning health information exchange, CRISP. During the COVID-19 pandemic, CRISP datahave the potential to serve an essential function in tracking and understanding the care and outcomes ofCOVID-19 infections. This resource would be unique among COVID registries in that it includes all healthevents and findings among the entire population of a geographic area, regardless where a health service wasdelivered. As such, it is ideally suited to address questions of health disparities. The Specific Aims of thisadministrative supplement are to (1) develop the CRISP data resource as a unique, population-based COVID-19 registry on the highly secure Johns Hopkins Precision Medicine Analytics Platform, and (2) evaluateCOVID-19 care and outcomes by race, neighborhood and socioeconomic status such that targeted strategiescan be deployed to reduce emerging disparities.",2020,2021,Johns Hopkins University,492704,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C06861,3UH3HL141800-04S1,A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION,"PROJECT Summary: The primary goal of this one-year competitive revision is to assess the potential of two novel therapeutics(DS-iKL and DAPT) to mitigate the extrinsic and intrinsic cardiac effects of SARS-CoV-2, respectively. This isimportant because, while acute respiratory distress is a major cause of morbidity and mortality of COVID-19,the clinical disease caused by the SARS-CoV-2 coronavirus, it has more recently become widely evident thatother organ systems are involved including the heart and blood. For example, cardiac arrhythmias are a majorsource of morbidity and mortality (44-60%) associated with COVID-19 disease, especially in individuals withpre-existing cardiovascular disease in ICU settings. Two recent reports have indicated that 20-22% ofhospitalized patients with SARS-Cov-2 experience cardiac injury, and these patients suffer a staggering 50%mortality rate, more than an order of magnitude greater than those patients without cardiac injury. Cardiacarrythmias or myocardial injury are acutely life threatening and can be caused by a host of factors including co-morbidities (e.g., hypertension), drugs, but also viral infection and systemic inflammation. In addition, a stateof hyper coagulation has also been described as a central feature of COVID-19, leading to blood clots that canbe life threatening as pulmonary emboli and right-sided cardiac failure. The specific aims of the project are to:1) Assess the potential of DS-iKL as a novel therapeutic to mitigate the cardiac effects of SARS-CoV-2 initiatedcytokine storm (coagulation and vascular permeability) using a multi-organ microphysiological system of iPS-derived human cardiomyocytes and vascular endothelium; 2) Assess the potential of the Notch signalinginhibitor, DAPT, on viral infectivity and thus intrinsic cardiac effects of SARS-CoV-2, in an organotypic tissueslice model of healthy and predisposed adult human cardiac tissue. We anticipate a rich data set resultingfrom these experiments that should demonstrate the exciting potential of DS-iKL and DAPT to mitigate theextrinsic and intrinsic cardiac effects of SARS-CoV-2. The research plan will also produce a path to in vivohuman studies to accelerate translation. Finally, the potential impact of DS-iKL and DAPT to mitigate theeffects of SARS-CoV-2 are likely to also be applicable to other inflammatory and infectious diseases that sharesimilar disease etiology.",2020,2021,University Of California-Davis,723616,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Clinical characterisation and management","Pre-clinical studies | Supportive care, processes of care and management",2017 +C06862,3R01MD012428-04S1,"Improving Minority Health by Monitoring Medicaid Quality, Disparities and Value","PROJECT Summary: Schizophrenia is a serious mental illness associated with a high burden of disease due to severe disability andpremature mortality largely driven by co-occurring chronic medical conditions that shorten life expectancy by atleast 20 years. The broad array of services needed by this population are primarily financed by Medicaid.Despite high costs, most patients do not receive recommended care, and minorities are less likely to do sothan whites. These pre-existing disparities and the profound social disadvantage also experienced by thispopulation make them particularly vulnerable to the devastation caused by the COVID-19 pandemic, which inthe US has been particularly severe in the state of New York. New Yorkers with schizophrenia, and minoritiesin particular, are not only a high-risk group for poorer COVID-19 outcomes but they may also experiencedeclines in their health due to disruptions in their ability to access healthcare. Although New York's Medicaidprogram authorized the use of telehealth to mitigate those disruptions soon after the Governor declared a Stateof Emergency in early March 2020, the degree to which telehealth has been adopted by Medicaid providersserving seriously mentally ill people and whether the effects of telehealth adoption may vary by race/ethnicityare not well known. Our proposed administrative supplement application builds on our ongoing NIMHD-fundedparent study (MD012428), which seeks to reduce healthcare disparities and thus improve health outcomes ofracial/ethnic minority populations through measurement of quality disparities and value (or cost-effectiveness)of Medicaid-financed care delivered to adults with schizophrenia. Consistent with the NIMHD's Notice ofSpecial Interest calling for studies of the impact of the COVID-19 outbreak on health disparity populations, wepropose to evaluate the effects of the outbreak on the racially/ethnically diverse population of Medicaidbeneficiaries with schizophrenia living in New York. In Aim 1, we will assess the effect of the outbreak onracial/ethnic disparities in access, quality, and effectiveness of mental and physical healthcare delivered to ourstudy population. In Aim 2, we will assess Medicaid providers' responses to the outbreak and their effects onhealthcare disparities in our study population. We will characterize provider response through a measure ofprovider readiness to adopt telehealth. Our general approach to assessing the impact of the outbreak onhealthcare outcomes and the impact of provider responses on those outcomes will involve the use of post-preoutbreak differences, interrupted time series approaches, as well as approaches that utilize time-varyingcoefficients. In all analyses, our primary interest are parameters that describe how race/ethnicity moderates theoutbreak's effect on outcomes and the providers' responses on outcomes. We expect that our work will providepolicymakers with a better understanding of the impacts of the outbreak on vulnerable populations and enablethe design of more effective policies to address this and future crises.",2020,2022,Rand Corporation,197215,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2017 +C06863,3UH3HL141799-04S1,MIcrophysiological systems to model vascular malformations,"PROJECT SUMMARYCOVID19 is caused by SARS-CoV-2, a novel member of the human coronavirus family that includes the closelyrelated SARS-CoV (SARS) and MERS-CoV (MERS) viruses. SARS-CoV-2 viral spike protein binds to humanangiotensin converting enzyme-2 (ACE2) on the surface of cells and is then primed by the serine/threonineprotease TMPRS22, whereupon the entire complex is internalized by the target cell. ACE2 is expressed bymultiple cell types of the body, including lung and gut epithelium (likely the primary sites of initial infection) andvascular endothelial cells (EC) of multiple organs. In addition to the well-described pneumonia-like diseasecharacterized by compromised lung function with subsequent depressed pO2 levels in blood, patients often alsoshow signs of multi-organ involvement, which can include gut, kidney, liver, heart, and brain. Most recently,numerous pediatric patients have been showing signs of Kawasaki disease, a systemic vascular inflammation.Over 30% of COVID19 ICU patients also show signs of thrombosis and 25% suffer venous embolism. Cerebralischemia, likely due to clot formation, has also been reported. What is not clear is whether this multi-organinvolvement is due to secondary infection of these tissues or whether these are all a consequence of systemichyperinflammation. The sequence of events that could drive systemic hyperinflammation stems from the SARS-CoV-2 mechanism of infection. Angiotensin II (AngII) is an important vasoconstrictor and under normalphysiological conditions its level is closely controlled through rapid degradation by ACE2, however, SARS-CoV-2 entry into cells clears ACE2 from the cell surface, potentially prolonging the action of AngII. Primaryconsequences of this would be two-fold: prolonged vasoconstriction in the lung (exacerbating poor oxygenationof the blood by the already compromised lungs) and a shift toward a pro-inflammatory state, as it is wellestablished that AngII can drive local vascular inflammation, in large part through the induction of IL-6 in EC andsmooth muscle cells (SMC). IL-6 is one of the major drivers of systemic hyperinflammation, and in its mostsevere form, a so-called ""cytokine storm"". IL-6 is also strongly correlated with thrombosis, likely throughupregulation of tissue factor on EC and macrophages, and by downregulation of thrombomodulin on EC.Through the parent award we have generated Vascularized Micro-Organs (VMOs), comprised of perfusedhuman vasculature and a surrounding stroma, and have further developed these into Vascularized Micro-Brains(VMBs) incorporating a Blood-Brain Barrier, and Vascularized Micro-Livers (VMLs). Additional cells, includingmacrophages and SMC have also been incorporated into the VMO. Using these platforms we will address threehypotheses: 1) That the VMO can be used to assess the ability of convalescent serum, soluble ACE2 or smallmolecule inhibitors to block entry of a SARS-CoV-2 pseudotyped virus; 2) That sustained AngII expression cantrigger a hyperinflammatory response from EC and macrophages; and 3) That hyperinflammation cancompromise peripheral and BBB vasculature as well as liver function.",2020,2021,University Of California-Irvine,179153,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2017 +C06864,3UH3HL141797-04S1,Lung-on-a-Chip Disease Models for Efficacy Testing (COVID-19 Competitive Revision),"PROJECT SUMMARY This COMPETITIVE REVISION application is being submitted to expand the scope of our ongoing NIHgrant UH3HL141797 in order to leverage our human organ-on-a-chip (Organ Chip) microfluidic culture devicesfor the rapid development and assessment of potential therapeutic agents for COVID-19. Our ongoing UH3grant supports the development of human Lung Chips as in vitro preclinical tools for rapid discovery of newtherapeutics for viral pandemics caused by influenza. In recent studies, we showed that highly differentiatedhuman cells in our Lung Chips, as well as human intestinal cells within Intestine Chips we developed, expresshigh levels of ACE2 and TMPRSS2 that mediate SARS-CoV-2 virus (CoV2) infection. We also were able toinfect these Organ Chips with CoV2 spike protein-expressing viral pseudoparticles (CoV2pp) that closely mimicthe effects of native CoV2 virus when tested against multiple FDA approved drugs in cell-based assays.Human Lung Chips were also shown to be more stringent models for assessing potential COVID19 inhibitoryactivity as only a subset of these drugs significantly inhibited entry of the CoV2pp when administered underflow on-chip at their maximum concentration (Cmax) in human blood reported in clinical studies. Here, wepropose to use human Intestine and Lung Chips in combination with computational discovery and syntheticchemistry approaches to develop broad-spectrum coronavirus therapeutics that would both help infectedCOVID19 patients now, and allow us to be prepared to prevent infections by related pandemic viruses thatemerge in the future. In preliminary studies, multiple novel compounds designed with our computational toolsexhibited significant inhibitory activities when tested against both CoV2pp and native CoV2 virus in cell basedassays. Thus, our Specific Aims include: 1) to use computational and synthetic chemistry approaches tocreate new compounds that are predicted to inhibit infection by CoV2 virus and related coronaviruses, 2) toprioritize active molecules by analyzing their structure-activity relationships in cell-based assays infected withnative CoV2 and related coronaviruses, 3) to identify lead compounds and effective doses based on inhibitionof infection and host inflammatory responses in human Organ Chips using native coronaviruses, and 4) tocarry out pharmacokinetic studies in mice coupled with iterative chemical synthesis and testing in cell-basedassays to optimize the pharmaceutical properties and safety of the lead compounds, while retaining efficacy.Through this effort, we will identify new compounds that demonstrate broad spectrum inhibiting activitiesagainst CoV2 as well as related coronaviruses, and generate pharmacokinetic data necessary to move thesedrugs into animal validation studies and, eventually, human clinical trials. This work will also further establishthe value of human Organ Chips as preclinical tools for accelerating drug development.",2020,2021,Harvard University,928351,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2017 +C06865,3R01AA026289-04S1,Effect of Alcohol Consumption on Molecular Risk Factors for SARS-CoV-2,"PROJECT Summary: SARS-CoV-2, the viral cause of Coronavirus Disease 2019 (COVID-19), is a highly contagious coronavirus,which upon infection results in a non-uniform distribution of clinical response. SARS-CoV-2 infects the lung andother organs, including liver and immune system, with non-lung infections contributing to the etiology of severeCOVID-19. Co-morbidity factors associated with poorer health outcomes include male sex, older age, anddisease. However, these do not fully explain the distribution of COVID-19 severity, suggesting additionalmodifying factors. Based on the molecular mechanisms mediating viral infection, excessive alcoholconsumption may be an unrecognized factor influencing SARS-CoV-2 infection. Spike proteins on the surfaceof SARS-CoV-2, and host serine proteases (such as furin and TMPRSS2) and ACE2-expressing receptor siteson target cells are required for SARS-CoV-2 infection. Conversely, ADAM17 (TACE), a major sheddase ofACE2, may lower infection. There is strong circumstantial evidence that alcohol directly increases risk forCOVID-19 by altering levels of the enzymes and membrane proteins essential for SARS-CoV-2 infection.Growth hormone/ insulin-like growth factor-1 (GH/IGF-1) and androgen signaling are disturbed by alcohol.GH/IGF-1 signaling is important for regulating levels of furin and ACE2. Androgen signaling is the only knownregulator of TMPRSS2 gene transcription, suggesting a plausible mechanism for male sex as a risk factor forsevere COVID-19. Additionally, alcohol lowers ADAM17 levels and increases levels of the adipocyte-derivedhormone leptin; Adam17 and leptin are important modulators of immune response to viral infection. Based onthe literature and preliminary data, we hypothesize alcohol consumption results in undesirable levels of plasmaand target cell membrane proteins necessary for or opposing SARS-CoV-2 infection. To test this hypothesis,we propose one Specific Aim: Evaluate the effects of alcohol - in the context of sex, age, and weight - onprotein and/or gene expression levels of molecular factors influencing SARS-CoV-2 infection (e.g., ACE2, furin,TMPRSS2 and ADAM17) in archived tissues (plasma, lung, liver, abdominal fat, and bone marrow) from maleand female rhesus macaques. The macaques were subjected to voluntary alcohol intake that mimics the fullrange of human drinking behavior (www.MATRR.com). The proposed research will provide insight into alcoholconsumption as a potential life-style factor for increasing risk for infection by SARS-CoV-2 and contributing topoorer health outcomes following infection. The research will also help identify potential interactions betweenalcohol consumption and intrinsic factors such as sex, age and weight in influencing COVID-19 outcome. Therequested supplement is a logical extension of the parent proposal (R01AA026289: Complex SystemsAnalysis of the Impact of Alcohol on Bone in Non-Human Primates) designed to: (1) determine the contributionof invariant intrinsic factors (e.g., age, sex, species) and variable extrinsic factors (e.g., drinking pattern) onorgan effects of alcohol (original focus on bone), and (2) identify the contribution of hormones/cytokines.",2020,2022,Oregon State University,73720,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2017 +C06866,3R24AA026801-02S1,Alcohol Misuse: An Independent Risk Factor that Increases the Incidence and Severity of COVID-19,"Abstract: The coronavirus disease 2019 (COVID-19) pandemic has resulted in unprecedented morbidity and mortality.Risk factors like age, obesity, and comorbidity impact the rate of SARS-CoV-2 infection and severity of COVID-19 leading to hospital ICU admission and death. Additional risk factors that promote exaggerated immune andinflammatory response to the virus leading to severe disease or death must exist. One such risk factor couldbe alcohol consumption because: (1) Alcohol is the most frequently used drug in the United States. (2) Patientshospitalized for pneumonia who have an alcohol use disorder (AUD) are at greater risk for developing AcuteRespiratory Distress Syndrome (ARDS) (the primary cause of death in COVID-19) than non-AUD patients; and(3) Alcohol negatively impacts function of the immune system and results in an inappropriate response topathogens (a primary mechanism of severe COVID-19 and ARDS); and (4) Alcohol disrupts the intestinalmicrobiome (dysbiosis) and intestinal and lung barriers which can both further promote inflammation andcontribute to ARDS. Accordingly, we hypothesize that alcohol misuse is an independent risk factor thatincreases the incidence and severity of COVID-19 by promoting exaggerated and dysregulated immune-inflammatory responses to SARS-CoV-2. We will leverage our COVID-19 data and biorepository at RushUniversity Medical Center (RUMC), which has tested over 22,000 patients (68% minority) with over 6000patients testing positive, over 1000 hospitalized, over 600 critically ill. Currently, all patients arriving at RUMCare screened for alcohol use with AUDIT. Our COVID-19 biorepository has banked nasopharyngeal swabs,serum/plasma, and peripheral blood mononuclear cells (PBMC). We will address the following Specific Aims:Aim 1: Determine if alcohol use or misuse increases severity of COVID-19 and elucidate interactionswith other risk factors. In this cross sectional study, we will use a machine learning classifier to determine ifincreased alcohol use/misuse are associated with more severe clinical presentation and poorer COVID-19health outcomes (in 12,000 RUMC, 6000 COVID-19+) patients. Aim 2. Determine the impact of alcohol useand misuse on COVID-19 disease course and the impact of COVID-19 on alcohol consumption. In thislongitudinal study, we will conduct longitudinal analysis of alcohol use in 6000 patients positive for COVID-19to determine: (2a) if alcohol use/misuse is associated with slower recovery from COVID-19-associatedsymptoms. Aim 3. Determine if alcohol misuse results in exaggerated immune-inflammatory responseto SARS-CoV-2 infection and more organ dysfunction in COVID-19 patients and explore themechanisms. In this mechanistic Aim, we will compare COVID-19 patients with different disease severity todetermine if alcohol misuse is associated with: (3a) altered immune/inflammatory response. (3b) disruptedintestinal barrier integrity. We will use machine learning and other advanced informatics approaches toinvestigate these Aims to discover new mechanisms for alcohol-COVID-19 interactions for prevention andtherapeutic targets for COVID-19.",2020,2024,Rush University Medical Center,313862,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2019 +C06867,3R61AT009867-02S1,Neural Mechanisms of Mindfulness-Based Cognitive Therapy (MBCT) for Post-Traumatic Stress Disorder (PTSD),"Abstract. Our funded R61 is an RCT of Mindfulness-based Cognitive Therapy (MBCT) for posttraumatic stressdisorder (PTSD) vs a well-matched comparator and pre-post fMRI. We are testing the hypothesis that MBCTengages a novel therapeutic mechanism involving increased capacity for metacognitive emotion regulation(""decentering""), and this is underlain by increased functional connectivity (FC) between the posterior cingulatecortex (PCC) and the dorsolateral prefrontal cortex (DLPFC). We hypothesized that MBCT-linked increases indecentering would reduce perservative negative thinking (PNT), a transdiagnostic process common to distressdisorders. However, at present our entire planet is caught in the grip of a global COVID-19 pandemic, which hasled to suspension of in-person research. Nearly half of US adults report negative mental health impact due toworry and stress over the virus, and disease and social burdens of the COVID-19 pandemic, as well as stressfrom the resulting economic downturn are profoundly impacting mental health. The state of Michigan (>52KCOVID-19 cases/>5K deaths) is among the most impacted ""hot zones"" in the US. Communities with highdensities of low-income African Americans are the hardest hit and disproportionately bear the brunt of thispandemic. African Americans account for 32% of all Michigan COVID cases and 44% of all COVID-relateddeaths, yet are only 14% of the Michigan population. Wayne County, which includes the city of Detroit, is thesingle hardest hit location in Michigan, with >19K cases and >2K deaths. African Americans are also oftenexposed to everyday racial discrimination, a prevalent and pernicious form of psychological stress, and havehigher rates of physical health disorders that amplify COVID risk. Childhood adversity, trauma exposures, andpoverty, disproportionately elevated in African Americans, as well as PNT, likely also substantially increase riskfor anxiety, depression, and SUD in the context of COVID-related stress. Mental health treatments are neededfor COVID-impacted individuals, especially low income African Americans who are disproportionately impacted;however, social distancing measures and increased financial insecurity create additional barriers. To adequatelyserve these communities we now face an urgent need to test the feasibility and efficacy of already validated,remotely-delivered stress management programs in health disparity populations. Such remotely deliveredinterventions, including MBCT, are feasible and recent data suggest are highly efficient and efficacious fordepression, anxiety, PTSD and SUD. Based on this evidence, we propose to conduct a RCT of remotelydelivered MBCT (N=30) & PMR (N=30) in underserved, trauma-exposed health disparity populationsdisproportionately impacted by COVID in South East Michigan. We will test hypotheses about the efficacy ofremotely-delivered stress management for COVID-related stress, anxiety and depression in this population, aswell as hypotheses about the specific psychological mechanism of MBCT, involving increased decentering /metacognitive emotional regulation, and how this relates to improvement in PNT and related distress.",2020,2021,University Of Michigan At Ann Arbor,157819,Human Populations,Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2018 +C06868,3R01AA026623-03S1,"Rural Southern Contexts, COVID-19, and Black Men'™s Alcohol Misuse","Project Summary/Abstract: The young Black men who are the focus of the proposed Urgent Competitive Revision to R01AA026623 arefrom small towns and rural communities in Georgia, an area of persistent poverty for Black residents thatcoincides with the nation's worst educational, economic, and health disparities by race. Black residentsaccount for more than 50% of Georgia's COVID-19 deaths, despite comprising less than 1/3 of the state'spopulation; the state's rural areas have a death rate 1.5 times that of its large cities. NIAAA reports that alcoholuse has increased since pandemic precautions (e.g., shelter in home, social distancing) have beenimplemented. Among rural Black men, we hypothesize that alcohol use may accelerate the spread of SARSCoV-2. In addition to effects on immune function, alcohol misuse undermines the judgement, self-regulation,and motivation to practice recommended disease mitigation behaviors (e.g., physical distancing, self-quarantine, hand washing). Alcohol misuse also encourages young adults' presence in settings andinteractions in which they may be likely to become infected or to infect others. We also propose to examine thepredictors of alcohol use. Many low-income Black men live below or near the federal poverty level and havefew financial resources, including economic assets to use during a protracted pandemic. Economic hardship isexacerbated by racial discrimination, family stress and conflict, fears of exposure to unsafe working conditionswhen work is available, and the greater likelihood that they, their families, or their friends will be affecteddirectly by SARS Cov-2 infection. Pandemic-related stressors are expected to foster the onset of alcohol useproblems and the amplification of existing problems. Importantly, many men will cope well, avoiding alcoholmisuse by drawing on both personal and social coping resources to deal with stress without alcohol use. Wepropose to conduct 3 remote surveys at 3-month intervals with a subsample (N = 242) of rural Black men froman ongoing study who provided past year, pre-pandemic data for the parent study. We will document men'sface-to-face social network contacts, COVID-19 mitigation behaviors, pandemic-related stressors and copingresources, and alcohol use. Our aims are to (a) model alcohol misuse trajectories among rural Black menduring the course of the pandemic, (b) investigate the influence of alcohol misuse, over time, on men's SARSCoV-2 transmission risk, and (c) investigate risk and protective processes associated with change in alcoholuse during the pandemic.",2020,2023,University Of Georgia,148354,Human Populations,Black,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2018 +C06869,3R01AA025854-04S1,Alcohol and the alveolar epithelial barrier,"Project Summary: The COVID-19 pandemic represents the most significant public health crisis to occur in generations. A majorcause of death due to COVID-19 is acute respiratory distress syndrome (ARDS). Whether chronic alcohol usedisorder exacerbates the severity of COVID-19 is not known, but is highly likely given the known impact ofalcohol on several organ systems including priming the lung epithelial barrier for increased paracellular leak. Inaddition, it is well established that chronic alcohol consumption exacerbates the severity of lung injury whencombined with an additional insult, a so-called ""second hit"". Of note, alcoholic lung syndrome increases theincidence of ARDS by 3-4 fold when compared with non-alcoholic ICU patients. We have identified propertiesof SARS-CoV-2 that predispose it towards a milder phase of infection, related to the virus E protein. Theoriginal SARS coronavirus, SARS-CoV-1, has an E protein that specifically targets tight junction protein PDZbinding motifs and thus readily disrupts the epithelial barrier of infected epithelia. By contrast, the COVID-19virus SARS-CoV-2 has E protein mutations that inhibit its ability to bind to PDZ binding motifs which can helppreserve infected epithelial cell barrier function. However, SARS-CoV-2 in the context of alcoholic lungsyndrome is more likely to result in a more severe outcome, since the epithelial barrier is already impaired as aresult of chronic alcohol abuse. Primary human bronchiolar epithelial cells derived from alcoholic and non-alcoholic subjects will be infected with SARS-CoV-2 in vitro and we will measure several outcome variablesrelated to severity of infection. We also have preliminary data showing that cells from alcoholics retainsignature differences in gene expression and function relative to non-alcoholic cells, leading to decreasedbarrier function and altered cell morphology. This supports a hypothesis that chronic alcohol exposure inducespersistent, epigenetic changes to the airway epithelial cell genome. In this supplement proposal, we willdetermine the impact of SARS-CoV-2 on the epigenome of host cells from alcoholics and non-alcoholics,focusing on DNA methylation. Of particular interest will be to examine the impact of DNA methylation inducedby alcohol and/or SARS-CoV-2 infection on the expression and downstream targets of the transcription factorsNrf2 and PU.1, known to be impaired by chronic alcohol exposure and that play key roles in regulatingepithelial antiviral responses. We will also identify novel host genome loci showing patterns of differentialmethylation that correlate with disease severity. We anticipate that identifying differentially methylated lociimpacted by chronic alcohol exposure and SARS-CoV-2 infection will lead to drug targets with the potential toreduce the severity of COVID-19 in alcoholic patients.",2020,2022,Emory University,146791,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2017 +C06870,3R01AI100272-09S1,Rapid production of SARS-CoV-2 molecular clones using CRISPR-based yeast recombineering,"Objective: We propose to construct and distribute a series of SARS-CoV-2-derived molecular clones usingpowerful genome assembly and rapid CRISPR-based manipulation methods available in the yeastSaccharomyces cerevisiae. We will develop and apply methods to mutate and tag each of the 18 viral proteinsin the context of a full-length viral cDNA clone from which virus can be produced and studied. Our two-PI UCSFteam marries decades of experience in virology and yeast molecular genetics.Rationale: Coronaviral replication is a complex process involving numerous viral and host factors. While thereis a strong foundation for studies of SARS-CoV-2 from prior studies of SARS, MERS, and other family members,there is no substitute for direct investigations of the virus responsible for the current pandemic. To date, therehas been only one report of the generational of a full-length replicating molecular clone of SARS-CoV-2. In thisapproach, Thiel and colleagues in Switzerland used a yeast transformation-associated recombination (TAR)vector to assemble an infectious clone of SARS-CoV-2 from overlapping DNA fragments. The Madhanilaboratory has 20 years of experience with recombinational cloning in yeast. We believe that the TAR approachcan be rapidly improved and extended to generate a series of clones useful for investigation of viral RNAreplication in a BSL2 context and the full viral cycle in a BSL3 context. The Andino lab has nearly 30 years ofexperience in molecular virology investigations. We propose to exploit the synergy offered by this team to rapidlydevelop, deploy and utilize a toolbox for investigations of SARS-CoV-2.Plan: To accomplish this goal we will 1) Improve the efficiency and utility of cloning in yeast. 2) Usetransformation-associated recombination and rapid CRISPR-based yeast recombineering to generate series ofmolecular clones in S. cerevisiae derived from SARS-CoV-2. 3). Test the role of viral proteins in RNA replicationand production of infectious virus. 4) Identify the protein interactome of viral proteins during a near-nativeinfection cycle. Importantly, all clones and viruses will be made freely available to the research community.Impact: These resources and methods are anticipated to accelerate the development of rationally-engineeredattenuated viral vaccine candidates, enable the rapid testing of antiviral compounds candidates using reporterviruses and increase fundamental understanding of the SARS-CoV-2 virus.",2020,2022,University Of California-San Francisco,620877,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C06871,3UH3DA044822-04S1,Learning from the COVID-19 pandemic to improve emergency management planning for harm reduction services in rural Ohio,"PROJECT SUMMARYCOVID-19 has been devastating in many areas of the United States. Both the disease itself and the necessarymitigation measures have affected local communities. Local health departments have struggled to identifyways to continue to serve their communities. One population that has been affected in multiple ways is peoplewho inject drugs (PWID). In many rural areas, harm reduction services have been closed because of theresponse to COVID-19, isolating many PWID. Some health departments have noted the absence of a clearemergency response plan to continue serving the vulnerable PWID population. Building on our relationshipsthat we have established in our UG3/UH3 Rural Opioid Initiative project, referred to as the Ohio Opioid Project(OHOP), we will assess the impact of the COVID-19 pandemic on local stakeholders and PWID in southernOhio. We will then use this information to develop an emergency management plan for two local healthdepartments that provide the only syringe service programs in the area. This plan will form the basis of ageneralizable approach that can be used elsewhere in rural areas of the U.S. The aims for this supplement areto: Aim 1) Explore the impact of COVID-19 on PWID and harm reduction services to identify strengths andgaps in emergency preparedness in Scioto and Gallia Counties (Step 1, PHEPARC). Aim 2) Assess the impactof COVID-19 on overdose and infectious diseases among PWID (Step 1, PHEPARC) Aim 3) Develop anemergency management plan for harm reduction and treatment services for use in Ohio and other states. InAim 1, we will assess provider preparation, unanticipated and anticipated challenges, and the impact onservices in the immediate aftermath of the pandemic. We will conduct 30 in-depth interviews with PWID and 30in-depth interviews with substance use providers, first responders, and state and local emergency responseofficials. In Aim 2, we will explore PWID's experiences with stigma, injection networks, overdose, syringeaccess, and access to care for MOUD and other health care through our respondent-driven sampling (RDS)survey. In Aim 3, we will draw from Aim 1 and 2 findings and work closely with the Ohio governmentalagencies, local health departments, and our community advisory board to develop a flexible emergencyresponse plan that can address the unique needs of rural counties. The plan will include a decision structure,communication plan, and detailed guidelines for substance use providers to mitigate the impact of futurecrises. Upon completion of this supplement, we will have a clear understanding of the impact of the COVID-19pandemic on PWID and harm reduction support in rural Ohio. And we will provide a strategy to mitigate theimpact of future crises on the rural PWID population in the future.",2020,2022,Ohio State University,138423,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C06872,3U19AI144301-02S1,Immune Cells and Secretory Pathways Leading to Human Systemic Autoimmunity,"Abstract: As the COVID-19 pandemic was considered to have a limited impact in children, a severe multi-inflammatorysyndrome that specifically affects children (MIS-C) has recently emerged. MIS-C phenotypes include acombination of typical/atypical Kawasaki disease (KD) and toxic shock syndrome. Unlike adults with COVID-19,however, most children display gastrointestinal symptoms but fail to present significant respiratory involvement.A subset of patients develops coronary artery aneurysms, as seen in KD. Importantly, while a large body ofstudies on adult responses to SARS-CoV-2 is being reported, knowledge gaps about the immune responses toSARS-CoV-2 in children remain disproportionally large. We hypothesize that a comprehensive systems analysis approach that incorporates high-resolutionimmunologic assays is required to efficiently identify the most relevant immune factors that contributeto the pathogenesis of COVID-19 related-MIS-C and to determine its subsequent outcomes. For thesereasons, we have assembled an experienced multidisciplinary team to study COVID-19 related MIS-C. We willleverage expertise in pediatric clinical research together with application of high-resolution multi-omics andanalytical tools to characterize the immune system dysregulation underlying MIS-C. Towards this end, we willexamine longitudinal samples and will compare the results with those of matched healthy controls with andwithout previous exposure to SARS-CoV-2. This study offers a unique opportunity to carefully dissect thecontributions of the different components of the immune system to the most severe form of SARS-CoV-2 responses in children. Our specific Aims are 1) to define the clinical variables and risk factors associated with MIS-C andestablish a longitudinal sample biorepository, 2) to identify innate immunity parameters associated withSARS-CoV-2 infection-related MIS-C, and 3) to characterize specific anti-SARS-CoV2 adaptive immuneresponses in patients with MIS-C.This proposal will address major knowledge gaps in MIS-C pathogenesis in children. Completion of the projectgoals will lead to better understanding of dysregulated immune pathways and to the identification of novelbiomarkers and therapeutic targets for this new syndrome.",2020,2022,Weill Cornell Medicine - Cornell University,2419315,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +C06873,3U19AI142731-02S1,A CETR-based partnership accelerator for rapid drug development targeting SARS-CoV-2 and pan-CoVs,"Summary: The unprecedented COVID-19 global health crisis is fueled by the absence of an effective vaccine and no specificantiviral drugs. Consequently, major research efforts have focused on identifying efficacious therapies. The mosteffective short-term solution is repurposing and repositioning of approved drugs or clinical-stage drug candidates,as this approach shortens the time to the clinic. Furthermore, as there are no drugs against any zoonoticcoronaviruses associated with human respiratory infections, pan-coronavirus drug regimens are vital to counterfuture outbreaks. To best address this urgency, a drug development Accelerator has been established as aformal partnership between our NIH Center of Excellence in Translational Research (CETR) and Merck andCo., Inc., a global leader in the discovery and development of antiviral drugs. The CETR program, which isfocused on novel and repositioned drugs against high-threat bacterial infections, provides a comprehensiveplatform for drug discovery. Merck brings a full complement of approved antiviral drugs and advanced candidatesfor repurposing and repositioning, with an emphasis on novel nucleoside and protease inhibitors. Firstly, smallmolecule compounds representing both FDA approved drugs and clinical stage drug candidates discoveredagainst other viruses will be evaluated in viral cytopathic and neutralization assays to assess inhibition of SARS-CoV-2. Lead candidates will be assessed for EC50/90/CC50 values, ADME pharmacokinetics, and safety todetermine their potential for immediate use in therapy. If data supports a robust therapeutic window, thenrepurposed compound(s) will be submitted for an IND under FDA EUA. A rodent model utilizing SARS-CoV-2infection will be used to assess in vivo PK/PD parameters supporting clinical dose ranging and safety margins.Secondly, a pan-coronavirus drug development candidate will be identified from either drug repositioning or fromMerck's focused compound libraries for existing antiviral classes discovered against other conserved viraltargets, as well as new lead series to host and viral targets representing >65 mechanisms of action. Thesecompounds will be screened in a high throughput virus challenge assay. SAR will benefit from the multi-millioncompound Merck sample collection via in silico substructure and similarity searches. Lead compounds will beassessed for robust in vivo therapeutic efficacy against SARS-CoV-2; metabolic stability, toxicity, ADME,rodent tolerability; pharmacologic properties consistent with QD or BID dosing, and acceptable safetymargins supportive of initiation of first in human clinical studies. The ultimate goal is the identification ofdevelopment candidates that can enter preclinical IND enabling safety derisking studies. This is anunprecedented public-private partnership for drug discovery The goal of this drug Accelerator is to identify arepurposed compound(s) that can treat COVID-19 patients within 4-6 months and by the end of Year 2, identifycandidates with pan-coronavirus efficacy that can enter preclinical IND-enabling and derisking studies.",2020,2021,Hackensack University Medical Center,619850,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C06874,3R01AA025956-03S1,Adult Social Networks and Well Being,"PROJECT SUMMARY The proposed project will significantly advance the understanding of the impact of COVID-19 relatedmitigation strategies on isolation, loneliness, alcohol use, alcohol use consequences, and mental health andphysical health outcomes by using social network analysis to investigate how isolation and personal networksare related to patterns of drinking over time. Isolation and loneliness are both known to negatively impact a rangeof health outcomes and health behaviors; while prolonged COVID-19 related stay-at-home orders will increaseisolation, it is unknown what impact they will have on loneliness or the other identified outcomes, which groupswill be most susceptible to negative outcomes, or whether changes in alcohol use will be temporary or long lived.The fields of alcohol research and prevention may see substantial benefit from the use of novel methodologicaltechniques to develop models that may provide a clearer understanding of the ways in which physical isolationand related mitigation strategies impact adult drinking. Specifically, the proposed project will: 1) assess how COVID-19 related changes in physical isolation,perceptions of loneliness, and social support exchanges (emotional and instrumental support) are linked tochanges in mental health, physical health, and alcohol use and consequences in a nationally representativesample of N=1,771 30-80 year olds; 2) determine the relative importance of a range of structural and behavioralpersonal network characteristics on changes in mental health, physical health, and alcohol use andconsequences during COVID-19; and 3) examine the role of COVID-19 related changes in physical isolation,loneliness, and social support on mental health, physical health, and alcohol use and consequences disparitiesby sex, race/ethnicity and economic status within and across two stages of the adult lifespan (mid- and later-life), and identify adults who are more resilient versus vulnerable to COVID-19 related impacts. To do so, we propose to add two surveys to our ongoing data collection for R01AA025956 that specificallyexamine COVID-19 related changes in physical isolation, loneliness, social support, personal and networkalcohol use, and alcohol use outcomes. With this additional data collection, we will have five waves of data onthese measures, spanning critical phases of the COVID pandemic: pre-COVID (Parent project Wave 1, reflectingApril 2019 behaviors), early-COVID (Parent project Wave 2, reflecting April 2020 - during the rollout of distancingguidelines), mid- and late-COVID (2 supplemental surveys: August 2020 and February 2021, likely during easingof current restrictions), and post-COVID (Parent project Wave 3, reflecting April 2021). The study will provide new insights into the role of isolation, loneliness, and social support on alcohol use,and associated health-related disparities, subsequent to pandemic-related mitigation strategies based onisolation. Additionally, data from the study will eventually be made publicly available and other researchers willalso be able to continue to survey the same panel, providing an ongoing resource for the scientific community.",2020,2023,Rand Corporation,100000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2018 +C06875,3UL1TR001857-05S2,2) University of Pittsburgh Clinical and Translational Science Institute,"Abstract: The pandemic caused by the SARS-CoV-2 virus continues to impact public health and the health of individuals,families, and communities. Those with a rare disease may be disproportionately affected because they mayhave a high risk of exposure to SARS-CoV-2 from their caregivers, housing situations, and need to attend in-person medical appointments. They may also be particularly vulnerable to complications from infection due totheir underlying disease condition, immunosuppressive therapies, genetic susceptibility, and/or other factors.The scope of infection among those with rare diseases is unknown. The present proposal will investigate thesero-prevalence of immunity against SARS-CoV-2 among asymptomatic individuals with rare diseases.Specifically, this study will determine the prevalence of detectable antibodies to SARS-CoV-2 (Aim 1) andinvestigate the immune attributes associated with health outcomes across the life course (Aim 2) amongasymptomatic individuals across the United States with one of >280 rare diseases. The anticipated results willprovide crucial insights into the magnitude of the COVID-19 pandemic in the context of rare disease and willcontribute to the identification of potential targets for a vaccine.",2020,2021,University Of Pittsburgh At Pittsburgh,842907,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility | Disease surveillance & mapping,2020 +C06876,3U01HL146208-02S3,"COVID-19 and the MWCCS: Psychosocial and Structural Impact on Physical and Mental Health, and HIV Prevention Behaviors","MACS/WIHS Combined Cohort Study (MWCCS) Administrative Supplements for the proposedproject, ""COVID-19 and the MWCCS: Psychosocial and Structural Impact on Physical andMental Health, and HIV Prevention Behaviors""Abstract. Older adults and people with comorbid conditions are at increased risk for severe illness fromCOVID-19. Given the older age of our research participants and the higher prevalence of comorbidconditions among people living with HIV (PLWH), PLWH are at increased risk for severe disease outcomesresulting from COVID-19. However, while many of our MWCCS research participants may not have testedpositive, mental health challenges, social isolation and psychosocial stressors may have disproportionallyimpacted access to health care, health outcomes and prevention behaviors. Qualitative interviews will allowfor in- depth accounts and perceptions provided by participants, sharing their experiences of dealing withthe COVID-19 pandemic and associated risks and restrictions. The proposed research will provide criticalinsights into the multilevel impact of the COVID-19 pandemic and its associated public health orders on thehealth and well-being of PLWH and those at-risk for HIV across the U.S. Results from this study willelucidate unforeseen consequences of public health efforts on vulnerable populations that are at higherrisk for comorbidities, stigma and discrimination and socioeconomic hardship. Data from this study will helpto inform future studies and public health efforts to prepare for interruptions in health care and studyparticipation due to natural disasters or public health emergences.",2020,2026,University Of Pittsburgh At Pittsburgh,22649,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Drug users | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C06877,3DP2HG010099-01S2,In situ functional genomics to understand transcriptional regulation,"PROJECT SUMMARY The COVID-19 pandemic has taken the lives of nearly 500,000 people worldwide in the span of a few months.Recently, a novel isolate of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) hasemerged and rapidly surpassed others in prevalence, including the original SARS-CoV-2 isolate from Wuhan,China. This Spike variant is a defining feature of the most prevalent clade (A2a) of SARS-CoV-2 genomesworldwide and, recently, we and others have demonstrated this variant leads to virions with an ~8-fold increasein human cell transduction. This is the first experimental evidence of a SARS-CoV-2 population variant acting ina gain-of-function manner. Although there are hundreds of Spike variants now in circulation, we lack tools for high-throughputcharacterization of these variants and their virulence. Here, we propose to develop a massively-parallel, high-throughput approach to test all Spike variants using a pooled forward genetic screen, examine the impact ofthese mutations on proteolytic cleavage of Spike and on ACE2 receptor binding kinetics, and validate changesin viral transduction with live SARS-CoV-2 via an innovative trans-complementation assay. Our proposed studies aim to understand the interactions between Spike protein variants and host (human)cell infection and their underlying biochemical mechanisms. This research will enable us to predict whetherparticular Spike variants can drive more serious COVID-19 outbreaks.",2020,2021,New York Genome Center,518550,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +C06878,3U54MD010722-05S1,Center of Excellence in Precision Medicine and Population Health,"The COVID-19 pandemic is not affecting everyone equally. In Nashville, Tennessee, the number of confirmedCOVID-19 cases are higher in ZIP Code regions that are burdened by poorer social determinants of health andhigher rates of conditions such as asthma. To allow for safe, effective, and physically distant care,telemedicine has emerged as a modality for preferred health care delivery. However, telemedicine requiresaccess to technology, broadband internet access, technologic literacy, and in many cases, English proficiency.These are often inaccessible to vulnerable populations who, additionally, may have privacy concerns and beless trusting of telemedicine. Now that the Health and Human Services (HHS) guidelines for telemedicine arerelaxed, creating greater ease for lower income diverse populations to access this modality from their home, itmust be built to ensure access equity that allows for a more precise tailored approach. Despite indications thatchildren are less often infected with COVID-19 than adults, utilization of overall child health care hasdecreased substantially since the pandemic gained traction with physical distancing requirements, but the useof telemedicine in children has not increased. This is especially true if those children are from underrepresented minority populations. We propose an administrative supplement to understand what makestelemedicine feasible and acceptable in underserved populations. In Aim 1, we will randomly select VanderbiltPediatric Primary Care patients who live in ZIP Code regions reflective of racially and ethnic diverse patientfamilies with higher social needs (N=500) and measure retrospective telemedicine utilization during the earlyperiod of the COVID-19 pandemic (from March 1- June 30, 2020). We will conduct a 30-60 minute telephonicsurvey in the participant language of choice (English, Spanish, or Arabic) to assess telemedicine utilization,knowledge, interest, accounting for social determinants of health, COVID-19 impact, technology access,race/ethnicity, and patient trust. We will then use the knowledge gained to prospectively design and testmodified telemedicine approaches, assessing the feasibility and acceptability of telemedicine visits provided to100 low-income pediatric patients (50 English and 50 non-English). Process data collected will include selectedtelemedicine platform (of the HHS accepted choices), visit length, and patient-family and provider satisfaction.Qualitative data collected will identify both patient-family and provider barriers and facilitators. These data willinform policies and processes to create equitable telehealth approaches for diverse pediatric populations.",2020,2021,Vanderbilt University Medical Center,211245,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Other secondary impacts | Health service delivery,2016 +C06879,3R41AG062023-02S1,"Continuous Monitoring of COVID-19 Symptomatology for Elderly Patients in Long Term Care Facilities Using Advanced, Soft, and Flexible Sensors Mounted on the Suprasternal Notch","Project Summary: COVID-19 is significantly more lethal in the elderly1 with thegreatest risk in those cared for in long-term care facilities (LTCs) where mortality ratesrange from 19% to 72% worldwide. Monitoring COVID-19 infections in LTCs remains aparticular challenging. The existing and a continued expected shortage of sufficientmolecular COVID-19 testing coupled to false negative rates as high as 15% necessitatesa critical need for new and complementary technologies that can surveil, alert, and trackCOVID-19 infections in this population. Our group are pioneers in the development ofnovel soft electronics. Our recent publication, supported by our active Phase I STTR,was published in Nature Biomedical Engineering detailing a next generation ultra-lowprofile, soft, and flexible sensor (ADAM) that continuously measures subtle acousto-mechanic signals generated by the body via an embedded high-frequency, 3-axisaccelerometer in direct mechanical communication with the skin. The ADAM sensorcommunicates via Bluetooth with our custom mobile application for real time streamingas well as on sensor data storage enabling stand-alone operation. All data streams arecloud synchronized (HIPAA compliant). The highly novel soft, flexible nature allows forthe ADAM sensor to be mountable on unusual locations of high information density.Specifically, we exploit the SN-the only location on the body where there is nodampening effect at the skin level with the intrathoracic cavity. This enables a SN-mounted ADAM sensor to capture heart rate (HR), respiratory rate (RR), temperature,physical activity (PA), swallow count, and talk time, along with additional novelrespiratory biomarkers relevant to COVID-19. In this proposal, we propose to develop anew COVID-19 software package, machine learning enhancements to our coughalgorithm, and validation in LTCs with both elderly patients and staff to evaluateusability, feasibility, and adherence. The high level of technology readiness with partnerLTCs allows us to deploy efficiently to generate essential data for a future FDAEmergency Use Authorization. Our team of experts in engineering, dermatology,gerontology, and machine learning are highly qualified to develop this COVID-19surveillance system that offers both commercial and clinical value with broadapplicability to a wide range of other respiratory and chronic medical conditions after thepandemic subsides.",2020,2021,"Sonica, Llc",249304,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2018 +C06880,3R01AG058673-03S1,Development of NLRP3 inflammasome inhibitors towards Alzheimer's disease,"The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2). One of the pathologies associated with COVID-19 is pneumonia that quickly leadsto acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and ultimately patient death. Recentstudies suggested a critical role of the NLRP3 inflammasome, a multiprotein platform that tightly regulates theinnate immune response, in the development of ARDS/ALI in COVID-19. Dysregulation of the NLRP3inflammasome is responsible for the excessive production of pro-inflammatory interleukin (IL)-1β and IL-18, whchis involved in the uncontrolled inflammatory responses and cytokine storm. Therefore, development of NLRP3inhibitors (NLRP3is) represents a novel approach to mitigating ARDS/ALI in COVID-19 patients. Recently, wedeveloped novel small molecule NLRP3is that blocks the assembly and activation of the NLRP3 inflammasome,resulting in inhibition of IL-1β production both in vitro and in vivo. Studies in animal models of neurodegenerativedisorders demonstrated target engagement and in vivo efficacy, thus providing proof-of-concept for furtherdeveloping NLRP3is as therapeutics. Notably, our studies in experimental autoimmune encephalomyelitis (EAE),a mouse model of multiple sclerosis in which excessive inflammation is one of the prominent pathologies, showedthat the lead inhibitor reduced the severity of EAE both preventively and therapeutically. Treatment with this leadcompound also substantially reduced the type 17-helper T (Th17) cells that produce IL-17, indicating its potentialin restraining uncontrolled inflammation. The central hypothesis of this proposal is that aberrant activation ofNLRP3 inflammasome contributes to the induction of cytokine storm and development of ARDS/ALI in COVID-19, and its pharmacological inhibition with NLRP3is will prevent and reduce ARDS. With the current R01 support(R01AG058673), we have successfully developed selective NLRP3is from novel chemical scaffolds andidentified lead compounds with improved inhibitory potency and druggability. We also identified compounds asnon-selective NLRP3is to reduce the production of multiple pro-inflammatory cytokines including IL-1β, IL-6 andTNF-alpha. The goal of this supplement project is to test selective and non-selective NLRP3is as potentialtreatments for ARDS in COVID-19. Two specific aims are proposed in this application. In Aim 1, analogs basedon the newly identified chemical scaffolds will be designed and synthesized to identify candidates for in vivostudies. In Aim 2, the top candidate inhibitors will be studied to confirm the therapeutic efficacy to mitigate lunginjury in a mouse model of ARDS. The proposed research is highly significant because successful developmentof novel NLRP3is may provide promising candidates with translational potential for clinical management ofCOVID-19.",2020,2020,Virginia Commonwealth University,462952,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2018 +C06881,3U01CA213140-02S1,BMT Survivor Study-2 (BMTSS-2),"PROJECT SUMMARY / Abstract: The latest threat to global health is the ongoing outbreak of the respiratory disease named Coronavirus Disease2019 (Covid-19). Covid-19 is highly transmissible, causes relatively high mortality, and has spread globally inour highly interconnected world. As of 4/26/2020, in the US alone there were 963,168 confirmed COVD-19 casesand 54,614 reported deaths due to COVID-19, and the curve demonstrating cumulative cases shows noevidence of a plateau. The case-fatality rate in the US is currently ~5%, and there is emerging evidence that theelderly and those with underlying comorbidities are at higher risk of succumbing to COVID-19-relatedcomplications. Importantly, there is no information about susceptibility to this infection among other vulnerablepopulations, such as those with prolonged immune suppression after blood or marrow transplantation (BMT).BMT survivors are likely at higher risk for COVID-19 infection that the general population for the followingreasons: i) as part of the conditioning for BMT, patients are exposed to high doses of chemotherapy andradiation; ii) BMT has been increasingly offered to older adults and BMT survivors are aging; iii) BMT survivorsare at a higher risk of comorbidities (diabetes, hypertension, coronary artery disease, and heart failure); and iv)~40% of the allogeneic BMT recipients develop chronic graft versus host disease (GvHD), and receive immunesuppressive therapy to manage the GvHD for prolonged periods of time. The risk of COVID-19 infection and ofCOVID-19 infection-related complications as well as case-fatality rate in BMT survivors are not known. Thecontribution of comorbidities to COVID-related complications in BMT survivors is also unknown. We will addressthese gaps using a large cohort of allogeneic BMT survivors (n=2,060) who have already participated in BMTSS-2 (parent study U01CA213140, PI, Bhatia). These patients were transplanted between 1974 and 2014, at oneof 3 participating sites (UAB, COH or UMN) and survival of ≥2y after BMT. As a result of their participation, wenow have information on their sociodemographics, clinical characteristics and burden of morbidity. We have alsoenrolled a cohort of 1,150 non-cancer individuals to serve as a comparison group. We will use this rich resourceto A) Describe the risk of COVID-19 infection in allogeneic BMT survivors compared to controls; B) Amongparticipants with COVID-19 infections, compare the prevalence of severe complications in BMTSS-2 survivorswith controls; C) Describe the prevalence of financial and psychosocial distress among BMT recipients comparedto the controls; D) Identify BMT recipients at highest risk for COVID-19 infection and severe complications. Thiscohort will represent the largest and most comprehensive attempt at examining the health and wellbeing of BMTrecipients during the COVID-19 pandemic. Findings from this study will have direct relevance for prevention fromCOVID-19 infection of not only the high risk BMT recipients, but also other individuals with a compromisedimmune system.",2020,2021,University Of Alabama At Birmingham,148500,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C06882,3U01ES026721-04S1,Investigating Effect of Air pollution and Host Defenses in SARS-CoV2 infection,"It is estimated that while the majority of SARS-CoV2 infections in the ongoing coronavirus disease-2019(COVID-19) pandemic are asymptomatic or have mild symptoms, hospitalizations and mortality largelyoccurs in patients with co-morbid conditions such as obesity, diabetes and COPD. Our understanding ofthe role of environmental exposures in modifying the response to SARS-CoV2 is emerging and airpollution; smoking and vaping have been associated with worst outcomes of SARS-CoV2 patients. There isa time sensitive urgent need to understand host defense mechanisms which are compromised due toenvironmental exposures and may increase susceptibility to SARS-CoV2 infection. This competing revisionwill forge collaboration with expert in SARS-CoV2 research to expand our horizon in this critical area. Wewill test the hypothesis of targeting a host defense pathway which is compromised in air pollution that mayprotect and modify the response to SARS-COV2 respiratory infection. Through the parent U grant, we havedemonstrated that chronic exposure to PM2.5 has an overarching role in epigenetic reprogramming. Ourstudies have established that transcription factor Nuclear factor erythroid-factor 2 (Nrf2) is a key activator ofanti-oxidative, anti-inflammatory, and innate immune defenses. We and others have demonstrated inhuman biospecimens and animal models that chronic exposure to PM2.5 causes a decline in Nrf2 activitythat correlates with compromised innate immune defenses. In mice deficient for Nrf2 (Nrf2-/-), viral andbacterial infection causes oxidative stress, worsened lung inflammation, acute lung injury and greatermortality compared to wildtype mice. Genetic or pharmacological activation of Nrf2 pathway can rescuethese effects. Disruption of Nrf2 pathway has been shown to cause upregulation of angiotensin-convertingenzyme 2 (ACE2) which is the functional receptor for SARS-CoV2 entry into lung epithelial cells.Furthermore, hypomethylation in ACE2 gene has been demonstrated to increase ACE2 expression inimmunocompromised patients. The goal for this project is to investigate the crosstalk of air pollutionexposure, host defense and SARS-CoV2 infection. Preclinical testing of therapeutic efficacy of Nrf2activators will provide proof of concept for further development a novel drug target for prevention andtreatment of SARS-COV2 infection. The proposal will leverage expertise of our team on air pollution,respiratory diseases and an expert virologist with ongoing BSL-3 SARS-CoV2 research. Successfulcompletion of this project will provide proof of concept for future studies directed towards development of anovel strategy of targeting host defense for prevention and treatment of SARS-CoV2 infection insusceptible populations.",2020,2021,Johns Hopkins University,450313,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Environmental stability of pathogen",2020 +C06883,3R01AI150300-01S1,Role of SARS-CoV-2-mediated Type I IFN antagonism in individuals with Down Syndrome,"Project Summary Type I Interferons (IFN-Is) are cytokines with potent anti-viral and proinflammatory activities. As such theyare tightly regulated to provide enough antiviral effects while not causing over and health disrupting inflammation.Disorders where IFN-Is dysregulation is known to cause pathology are termed type I Interferonopathies. Down syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities inchildren and young adults with Incidence in US of about 1 in 600 individuals. Individuals with DS often havecardiac and gastrointestinal abnormalities. Additionally, they have a number of immune-related problems fromincreased susceptibility to an array of infectious diseases to autoimmunity. Unfortunately, the exact molecularmechanism leading to these immune defects has not been elucidated. COVID-19 is a disease caused by a coronavirus, Severe Acute Respiratory Syndrome (SARS) -CoV-2.Infections by SARS-CoV-2 are now present in every country around the globe, causing unprecedented publichealth burden. SARS-CoV is known to interfere with IFN-I induction and signaling. To which extent SARS-CoV-2 can cause illness in individuals with DS is currently unknown. DS is, in most cases, caused by an extrachromosome 21, on which the receptors for type I Interferons (IFNAR1 and IFNAR2) are encoded. How thisgene dosage effects are contributing to SARS-CoV-2 pathophysiology is not understood. This proposal is builtaround the hypothesis that relative amounts of IFNAR1 and IFNAR2 are the essential factors controlling SARS-CoV-2 pathophysiology. To address this hypothesis, we propose to study DS patients in vitro at the molecularlevel to determine the functional significance of dose of these genes in regulating IFN pathway in humans duringSARS-CoV-2 infection. Deeper understanding of molecular regulation of IFN-I in DS in the context of SARS-CoV-2 will allow us tobetter understand how to approach clinical management of disease.",2020,2024,Icahn School Of Medicine At Mount Sinai,255946,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C06884,3R44AG058272-03S1,A Device for the Prevention and Treatment of Multiple Organ Failure in COVID-19 Patients,"Abstract: Multiple organ failure (MOF) is a common cause of morbidity and mortality for individuals in the intensive careunit (ICU) including those suffering from COVID-19. Prevention of multiorgan injury and subsequent treatmentshould be a focus in the ICU, and is thought to be especially important in supportive care of critically ill patientsand COVID-19 patients. In efforts to prevent and treat MOF, the gut may be a key target as it is a driver of MOFdevelopment. Specifically, critical illness has the potential to compromise gut perfusion in many patients(including those with embolic or shock insult), which can propel a pathological responseinitiating systemicinflammatory response syndrome (SIRS)leading to MOF. A novel treatment may be direct peritonealresuscitation (DPR), which consists of circulating commercially available peritoneal dialysis solution throughoutthe peritoneal cavity. DPR improves tissue perfusion and reduces cellular ischemia. In turn, DPR has beenextensively proven to attenuate SIRS, increase blood flow in end-organs with corresponding decreased injuryand improve survival in preclinical small animal models of hemorrhagic shock (HS). Further, significant clinicalbenefits of DPR have been demonstrated in 1) improved recovery of patients requiring surgical management ofabdominal catastrophe (trauma, sepsis and necrotizing enterocolitis) and 2) significantly increased numbers oforgans transplanted from brain dead, heart beating donors. However, the risk of injury-related complicationsduring peritoneal access is a substantial roadblock to the clinical utility of DPR, especially for unstable, criticallyill patients, who require peritoneal catheter placement to be quick, safe and conducted at the bedside. To bringthe benefits of DPR to the ICU, TheraNova has developed the Multi-Organ Failure Treatment (MOFT). MOFThas two functions: 1) safe, quick bedside access through the use of a proprietary Peritoneal Access System(PAS), and 2) autonomous DPR through the use of a Lavage Controller (LC). In our preliminary work, we havedemonstrated 1) attenuated risk of tissue injury, 2) timely peritoneal access, 3) evidence-based insertionguidance, and 4) consistent, autonomous peritoneal lavage. The goal of this revision application is to validateMOFT in a clinically relevant and reproducible animal model before translation to clinical use. First, we willenhance device utility by optimizing the MOFT PAS controller to enable three modalities of evidence-basedguidance within a centralized hub (Aim 1). We will then conduct a randomized, controlled study with an HS swinemodel to demonstrate safe and effective peritoneal access (Aim 2.1) and DPR treatment for the prevention ofgut-derived systemic inflammation and organ injury (Aim 2.2). Successful completion of this proposed effort willprovide sufficient evidence to file for an Investigational Device Exemption with the FDA. We will then initiate pilotclinical studies in the ICU and focus specifically on critically-ill patients with COVID-19.",2020,2021,"Theranova, Llc",398966,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2017 +C06885,3R01DE025001-05S1,Novel coatings to minimize surface degradation and fracture susceptibility of dental ceramics,"This R01 competing revision is focused on establishing the sensitivity of our novel sensor to the SARS-CoV2 protein antigen. This is a revision of our current aims in response to the NIH NIDCR NOSI for immediate and high impact research to help protect dental professionals in this COVID-19 pandemic. Our data using the plastic circuit board (PCB) sensor demonstrated capability to detect the S2 protein antigen of the SARS-CoV2 virus in concentrations as low as 0.7 fM. The long-term goal of this research is to develop a handheld, non-invasive, lowcost,point-of care, accessible sensor capable of detecting SARS-CoV2 in saliva for immediate identification of this disease. Our overall objectives in this application, which are the next steps toward attainment of our longterm goal are to: i) To optimize the analytical sensitivity and specificity of detecting SARS-CoV-2 virus in contexts relevant to clinical application and; (ii) To develop a miniaturized handheld sensor with sensitivity identical to the working PCB prototype, suitable for use in clinical field testing.This unique, translational research project is an alternative testing methodology to the current gold standard for COVID-19 of nasopharyngeal swab tests analyzed through reverse transcriptase polymerase chain reaction (RT-PCR), which is invasive and needs signal amplification of viral RNA for proper detection. Since this electrical sensor can detect the virus at such low concentrations, there is no need for amplification, and the result is rapid so individuals, particularly health care workers, can immediately implement quarantine and treatment strategies to prevent spread. The non-invasive methodology also makes periodic re-testing feasible and also allows identification of the asymptomatic reservoir in the population along with having the ability to monitor the progression of the disease through viral loading in saliva. To achieve this goal, we plan to ensure the specificity and sensitivity of the sensor to SARS-CoV2. In addition, we also plan to consolidate the electronic components into a smaller microchip to allow for portability and easy accessibility of the testing device. We propose thefollowing aims to test our central hypothesis: Aim 1: To optimize the specificity and sensitivity of SARS-CoV-2 antigen detection in human saliva using the PCB sensor platform. Aim 2: Develop a handheld sensor for qualitative detection of SARS-CoV-2 antigen in human saliva with performance specifications equivalent to the large-scale PCB prototype.",2020,2021,University Of Florida,219405,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2016 +C06886,3R44MD012279-03S1,Staying Connected: Community-engaged research to address the impacts of the COVID-19 Pandemic among transgender women through an m-health prevention program,"ABSTRACT: Staying Connected: Community-engaged research to address the impacts of the COVID-19Pandemic among transgender women through an mhealth prevention programThe COVID-19 pandemic has reminded the world that viral outbreaks are a reality and can quickly generate highlevels of mortality and morbidity, overwhelm health-care systems, and produce massive social and economicupheaval. Epidemiological data suggest that COVID-19 will have its most devastating impact on the mostvulnerable members of society, and in the process, exacerbate existing health disparities. In the United States,transgender women, and in particular transgender women of color, are particularly at risk for COVID-19 infectiondue to high levels of HIV infection, substance abuse, depression, anxiety disorders, and social isolation.Research demonstrates that these health disparities and vulnerabilities are connected to the multiple forms ofdiscrimination that shape transgender women's lives. In this context, the COVID-19 pandemic andaccompanying mitigation strategies affect not only COVID-19 transmission and disease, but also transgenderwomen's adherence to HIV anti-retroviral therapies, utilization of the HIV prevention continuum, financial andhousing stability, and anxiety and depression associated with the disruption of gender-affirming care. Thisproposed administrative supplement will build on our current project, Trans Women Connected (TWC), anmhealth sexual health promotion app for transgender women, by conducting research to gain greaterunderstanding of and ways to respond to these inter-connected and still evolving trans-specific COVID-19impacts. Specifically, we aim to: 1) Conduct rapid formative research to examine the impact of COVID-19 andmitigation strategies, including unintended negative consequences, on transgender women through focusgroups, expert advisors, and an engaged community advisory board; 2) Develop a culturally tailored, community-strengths and cognitive behavior theory informed module of interactive COVID-19 educational activities forintegration into the overall TWC mobile app. The skills-building activities seek to support COVID-19 mitigationstrategies, reduce COVID-19 morbidity and mortality, and in general, improve health care utilization, increaseself-care and resilience, and promote connectedness among transgender women, thereby leading to improvedoverall mental and physical health; and 3) Evaluate the impact of the COVID-19 module as part of the largerparent grant 2-arm cluster randomized controlled trial with 450 transgender women. This evaluation will enableus to collect data on COVID-19 and the impact of the mhealth module on transgender women over a 12-monthtime period likely encompassing relaxation of distancing measures, possible second and third waves of infectionsand additional periods of lockdown, and potentially, the emergence of a vaccine. The project offers the possibilityof unprecedented insights into effects of the COVID-19 pandemic on the health, connectedness, and behaviorsof one of the most vulnerable and socially marginalized populations in the US.",2020,2021,Dfusion Inc,178455,Human Populations,Other,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Communication | Indirect health impacts,2017 +C06887,3RF1AG057409-01S1,Dynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer's Disease,"COVID-19-Related Administrative Supplement to NIA RF1 AG057409 under PA-18-591 and NOT-AG-20-022Project Summary: Epidemiological studies of pandemic COVID-19 suggest that aged populations, especially those withAlzheimer's disease and related dementias (AD)/ADRD, are particularly vulnerable. We therefore propose anAdministrative Supplement for work in line with the Division of Neuroscience at NIA, namely, ""studies aimed atdiscovery and development of novel drugs, as well as repurposing and repositioning existing drugs, forpreventing and treating COVID-19, particularly drugs that are specific for COVID-19 related CNS targets andCNS mechanisms related to or driving the viral-mediated pathophysiology."" Specifically, we will test drugsdeveloped in the parent RF1 award by screening them for anti-viral activity to fight the infection andtreat potential CNS ramifications in AD/ADRD and aged populations. Intriguingly, aminoadamantanedrugs (e.g., amantadine, rimantadine, and memantine) were first discovered as anti-viral agents because theycan block the ion channel found in the envelope of viruses such as influenza, but also found in the SARS-CoVfamily. The PI, Dr. Lipton, subsequently found that these aminoadamantanes had activity in the CNS byblocking excessively-activated NMDAR-associated ion channels, and Lipton's work eventually led to FDAapproval of memantine for use in AD. Recently, the Lipton group designed and synthesized aminoadamantanenitrate drugs under the auspices of the parent RF1 Award to be used to inhibit excessively-activated NMDARsto a much higher degree than memantine by adding a nitro-based warhead to an aminoadamantane in order toS-nitrosylate (via covalent reaction of NO) and thus further inhibit receptor activity in a targeted fashion. As aseemingly amazing coincidence, it was recently reported that the SARS-CoV family of viruses are susceptibleto NO, in part by inhibiting their replication cycle. However, the delivery of NO or a NO-related species to analready ill patient could have severe consequences, such as lowering the blood pressure dramatically. Hence,in this proposal we develop a novel targeted delivery of NO-related species directly to the SARS-CoV-2 virusby using the aminoadamantane moiety that binds to the envelope ion channel and has a nitro-based warheadthat it then delivers directly to the virus. Another critical feature of the current proposal is that we use thesesame aminoadamantane nitrate compounds to protect the brain from injury potentially engendered by the virusvia inhibition of excessive NMDAR activity. Importantly, up to 37% of patients hospitalized for severe COVID-19 reportedly display neurological sequelae. Mechanistically in this regard, in the face of severe viral infections,including coronaviruses, excessive levels of glutamate are released (or not taken up) by astrocytes, leading toglutamate-related neurotoxicity (excitotoxicity). In our parent RF1 grant, we reported similar findings in AD, i.e.,that Aß-stimulated astrocytes release glutamate onto neurons. Therefore, this Administrative Supplement willtest the top 'hits' of aminoadamantane nitrates capable of inhibiting SARS-CoV-2 in additional screens for theirability to prevent viral-related damage to neurons in the brains of AD/ADRD and aged populations.",2020,2022,Scripps Research Institute,679644,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2017 +C06888,3R01HL139671-02S1,SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear imaging in Minority Populations) COVID-19 Suppplement,"Project SummaryCOVID-19 is a global pandemic that disproportionately affects minority older adults with cardiac disease andmultiple chronic conditions. Densely populated urban centers with a high proportion of socioeconomicallydisadvantaged persons, including New York City (NYC) and Boston, are most impacted by COVID-19. SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations, R01HL139671) is aNHLBI funded, prospective cohort study that enrolled 123 of a target 800 Black or Caribbean Hispanicparticipants over the age of 60 years with heart failure prior to the mandatory recruitment pause for thepandemic. The profile of the SCAN-MP participant matches those known to be at highest risk from COVID-19. In this application, we propose to leverage the successful recruitment and retention techniques of theSCAN-MP infrastructure to advance our understanding of the prevalence of SARS CoV-2 infection anddisentangle the demographic, social, and environmental factors known to be associated with infection. Whilemitigation is the primary public health strategy to address the spread of COVID-19, it may be particularlychallenging for those with resource limitations or those who live in close physical proximity to others to complywith CDC recommendations, perhaps accounting for the observed increase in infection rates. Successfulemergence from the pandemic will depend upon evidence of prior SARS CoV-2 infection in the population.Given that asymptomatic infection is common, serologic testing will likely play a critical role in the next phaseof recovery. Serologic testing has been validated at Columbia University with a highly sensitive and specific,quantitative ELISA-based assay to detect antibodies to SARS-CoV-2 that we propose to leverage in thisstudy. Our objectives are to (1) define the proportion of SCAN-MP participants with evidence of prior COVID-19 infection by antibody testing, (2) determine the capacity of SCAN-MP participants to comply with CDCmitigation recommendations. We will then explore how infection rate and mitigation compliance interact withsocio-economic factors such as income and living conditions, as well as measures of health literacy,trust/engagement in the health system, and perceived discrimination. We will explore whether the presenceand/or titer of antibodies specific for SARS CoV-2 virus will be associated with future COVID-19 infection aswell as adverse outcomes (hospitalizations and mortality) over a one-year time period. We are uniquelypositioned to perform these studies quickly given our ability to recruit an urban, minority cohort with cardiacdisease at high risk for COVID-19 morbidity/mortality, expertise in the performance of serologic testing forantibodies to SARS CoV-2, and established expertise in community engaged research. Successfulcompletion of these Aims has the potential to inform implementation of mitigation strategies in high-riskpopulations and contribute important data useful for the resolution of the COVID-19 pandemic.",2020,2021,Columbia University Health Sciences,176033,Human Populations,Black | Other | Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Indirect health impacts | Social impacts,2020 +C06889,3R01AI036082-28S1,Neutralization of Primate Immunodeficiency Viruses,"We will repurpose existing assays, techniques and expertise that are central to our project team's virology, structural biology, vaccine development and protein production skill-sets for HIV research, to now also work on SARS-CoV-2 during the COVID-19 pandemic emergency. These interactive research efforts will draw on our established methodologies and should represent a productive use of our existing NIH grant resources. We note that there continue to be institutional restrictions at all three performance sites on the effort that can be applied to our original goals relating to HIV-1 vaccine research and development. Those goals will be unchanged, but will be pursued at a reduced effort during the period when we also work on the new SARS-CoV-2 projects for which we have fewer institutional restrictions due to the COVID-19 pandemic.",2020,2023,Weill Cornell Medicine - Cornell University,177065,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,1994 +C06890,3R01LM012527-04S1,Uncovering Clinical Evidence in COVID-19 Publications: An Integrated Search via Text & Images,"Project Summary: Uncovering clinical evidence in COVID19 publications: An integrated search via text & imagesThe proposed research aims to develop and advance tools for using image-data appearing in scientificpublications, in addition to text, in order to expedite effective access to COVID-19 published information.Current efforts aiming to address the COVID-19 pandemic include devising treatment, understanding virusmechanisms, detecting infection and antibodies, and ultimately - developing a vaccine.All these efforts require effective access to biomedical information related to the virus. The Allen Institute hasrecently released the CORD-19 dataset - a large, continually updated collection of scientific literature pertainingto COVID-19 and Corona viruses. This dataset comprises tens of thousands full text articles, forming a basis fortext-mining tools that will support access to information pertaining to COVID-19.Notably, much of the evidence within these publications is provided in the form of figures. Furthermore, regionswhere such evidential images occur are rich in information.While biomedical text-based mining tools are being quickly developed and offered for accessing this dataset,images, which contain key clinical and biological information, are not considered. Even outside the COVID-19realm, little has been done so far to utilize images within publications, despite the fact that they provide importantcues about the relevance of the information embedded in articles.Our premise, which is supported by our own and by other informaticians and clinicians experience, is thatinformation derived from images can (and should) be directly incorporated into the biomedical - and specificallyinto the COVID-19 - document retrieval and extraction. Doing so will improve accurate access to relevantarticles, while pin-pointing significant evidence within them, and expediting access to much-needed criticalinformation. The work on this project will result in methods and tools that take advantage of both image- andtext-data, facilitating more effective and focused retrieval and mining, thus better supporting speedy data-intensive discovery in the context of COVID-19.",2020,2021,University Of Delaware,74999,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2017 +C06891,3R01MD012421-02S1,Influence of patient-centered HIV care on retention and viral suppression disparities,"Abstract: Antiretroviral therapy leads to viral suppression which not only prevents the progression of humanimmunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome and death among people livingwith HIV (PLH), but also prevents the transmission of HIV. Therefore, viral suppression is one of the keyindicators in the National HIV/AIDS Strategy for the United States. On March 12, 2020, the Mayor of Miami-Dade County declared a State of Emergency in the County due to the COVID-19 Public Health Emergency(PHE) and on March 25, 2020 advised all people 65 and older and those with health conditions, includingimmunosuppression, to stay home. These and other necessary steps to combat COVID-19 had a far-reachingimpact on HIV care; most HIV medical case management sites and HIV clinicians began delivering care viatelehealth or telephone, reducing the availability of in-person services. Furthermore, the ripple effects due tothe loss of the tourist industry and closure of nonessential businesses have led to widespread unemploymentand economic hardship within the community with 67,000 unemployment claims as of April 21st. The RyanWhite Program (RWP) serves about 52% of PLH in the United States and is the provider of last resort, servinguninsured and underinsured PLH. Thus, the RWP serves among the most socioeconomically vulnerable PLH.Anecdotal reports indicate that many PLH are struggling with the COVID-19 PHE-related changes in HIV caredelivery and are experiencing significant hardships such as food insecurity. The objective of this study is tocharacterize the COVID-19 PHE-related changes in HIV care delivery (e.g. use of telehealth and other remotemodes of delivery) and any related difficulties and the COVID-19 PHE-related socioeconomic and psychosocialhardships experienced by RWP clients and assess how these have affected HIV viral suppression amongRWP clients. A further objective is to compare the effects by racial/ethnic and gender groups to identify anypotential inequities. To accomplish these objectives, we will interview 300 RWP clients by telephone (130Hispanic, 100 African American, and 70 Haitians with roughly half men and half women in each group) abouttheir HIV care and COVID-19 PHE-related socioeconomic and psychosocial stressors and compare their HIVviral loads before and after the onset of the COVID-19 PHE. This study will provide important information abouthow the COVID-19 PHE is impacting viral suppression among RWP clients, and the extent to which COVID-19PHE-related stressors are novel barriers to care. Any inequitable impacts by race/ethnicity and gender will alsobe examined. This information is also critical, because due to the immune suppression experienced by manyPLH, it is likely that social distancing measures may be needed during HIV care delivery for an extendedperiod of time during the current pandemic.",2020,2023,Florida International University,163916,Human Populations,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2019 +C06892,3U19AI144306-02S1,Etiology and outcome of MIS-C,"Abstract: This proposal seeks to test two hypotheses regarding the Multisystem Inflammatory Syndrome(MIS-C) recently identified in children and young adults infected with SARS-CoV-2. Wehypothesize that there is a spectrum of disease from severe acute disease to MIS-C. SevereCov acute disease is associated with low interferon production, poor control of virus and agerminal center derived antibody response to the virus leading to long term immunity while MIS-C is associated with high interferon, efficient control of virus, but an extrafollicular derivedantibody response with poor long term immunity. We will test this hypothesis through a geneticanalysis, analysis of serum cytokines and analysis of anti-viral antibodies. We also hypothesizethat plasma metabolic profile of subjects with MIS-C will predict short term cardiac dysfunctionand long term cardiac damage.",2020,2021,Feinstein Institute For Medical Research,1491907,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C06893,3P01CA016038-45S1,"Molecular Basis of Cancer Virus Replication, Transformation, and Innate Defense","Coronavirus disease (COVID-19) and its causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently a most pressing health concern. Much more needs to be learned about the pathology of the virus, as well as the host response to viral infection. Acute respiratory distress syndrome (ARDS), the final state of severe COVID-19, is caused by the uncontrollable immune response of the host, so called cytokine release syndrome (CRS). What predisposes some patients to progress to severe COVID-19 is not known, but certain populations - such as the elderly and cancer patients - are at higher risk. Therefore, we are investigating whether host microRNAs (miRNAs) can serve as biomarkers for COVID-19 prognosis. Since miRNAs regulate virtually every cellular process, and are often dysregulated during disease, including viral infections, it is highly likely that SARS-CoV-2 infection impacts miRNA levels. Aberrant miRNA profiles during viral infection are known to be caused both by host responses to counteract the infecting agent and by deliberate actions of the virus, usually to dampen the immune system Our group has contributed significantly to the realization that some herpesviral transcripts selectively bind host miRNAs and induce their degradation in a process known as target-directed miRNA degradation (TDMD). Such selective miRNA degradation is beneficial for the virus, as exemplified by decreased levels of host miR 27a causing prolonged T cell activation that aids oncogenic transformation by herpesvirus saimiri. It is possible that SARS-CoV-2 selectively affects the miRNAs that regulate crucial cytokines, as many miRNAs are known to regulate immune factors involved in antiviral defense. One of these is a key player during severe COVID19: interleukin 6 (IL-6), which is regulated by miR-146a, miR-142-3p and let-7. Documenting the dysregulation of particular miRNAs during infection by SARS-CoV-2 can therefore have therapeutic potential, as well as providing biomarkers for COVID progression. We will use state-of-the art small RNA sequencing, as well as RNA detection by TaqMan reverse transcription quantitative PCR (RT-qPCR) to investigate miRNA populations at various times after infection of several lung cell lines with SARS-CoV-2. In addition, we are employing custom bioinformatic predictions to search for viral transcripts that could selectively regulate host miRNAs and have already identified several potential candidates. Providing fundamental insights into the biology of SARS-CoV-2 as regards these important host noncoding RNAs will be important for mankind's ability to manage both the current and future pandemics.",2020,2021,Yale University,55833,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity",2020 +C06894,3R01AI146079-01A1S1,Mitigating COVID-19 transmission in U.S. jails,"Project SummaryCongregate settings, such as large urban jails, have been significantly impacted by COVID. While preventionstrategies from hospitals can be implemented, there are unique challenges to preventing transmission withinjails that warrant additional attention. Our primary objective of this supplement is to model infection preventionand mitigations strategies for COVID in a large urban jail. Specifically, we will test strategies that have beenemployed at the jail at (1) admission to the jail, (2) during incarceration, and (3) at discharge to gauge theimpact each strategy has had and to forecast downstream impact of COIVID in jails. We will also examine theimpact of COVID spread in jails on the burden of infection in the community. One major strategy employedacross the country to reduce spread within jails is to encourage release of low-risk, nonviolent offenders.However, the downstream impact in the community of this intervention is unknown and it is critical to examinewhat intermediate steps may be necessary, i.e. a 'step-down' quarantine period. Given the central role the jailis hypothesized to play in propagating the spread of MRSA to high-poverty, inner-city neighborhoods, ourproposal to examine COVID has significant",2020,2023,Rush University Medical Center,255285,Human Populations,Unspecified,Unspecified,Unspecified,Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C06895,3R21HL140287-02S1,Step down of asthma biologics in real-world practice settings,"Our overall goal is to identify risk factors in people with asthma for being hospitalized for COVID-19. Our teamis uniquely positioned to quickly analyze pre-existing data that includes risk factors likely to be relevant forpeople with asthma who are hospitalized for COVID-19. Our team has used a claims data set that includes200+ million people residing in the US in multiple studies in people with asthma called OptumLabs DatabaseWarehouse (OLDW).We hypothesize that there are behavior, health care delivery, and patient demographic factors associated withhospitalization for COVID-19 in people with asthma. To test this hypothesis, we will analyze pre-existing datafrom OLDW, testing the following independent variables: age, sex, race-ethnicity, smoking, comorbid chronicdiseases, geographic region, rural/urban residence, access to provider care (traditional and telehealth),medication-filling behavior, and types of asthma medications filled.",2020,2021,Mayo Clinic Arizona,21370,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C06896,3R01AG058254-03S1,Understanding and addressing challenges to informed consent and research compliance during Covid-19 research,"PROJECT Summary: Within all US and international codes of research ethics, informed consent serves as a cornerstone for theethical conduct of research. The application to our current parent R01, ""Implementing Evidence-basedInformed Consent Practices to Address the Risk of Alzheimer's Dementia and Cognitive Impairment in ClinicalTrials"" (AG058254) reviewed a large body of literature and concluded that there are several evidence-basedpractices that improve the consent process: using plain language and optimizing consent document layout;assessing understanding of information using a validated instrument; reviewing with participants anyinformation that was misunderstood; and involving surrogate decision-makers as necessary. Our currentparent R01 has 3 specific aims-including development of a web-based toolkit and a social media push-thatcollectively aim to increase the implementation of these evidence-based consent practices (EBCPs).Implementing EBCPs is made more difficult in times of pandemic. Severely ill patients may be unable toconsent, yet quarantine prevents access to surrogates. Electronic consent forms may need to be used,because researchers may not be allowed to enter rooms with patients. These electronic consent forms mayneed to be produced very quickly, with little attention given to plain language and formatting. Consentinformation may be incomplete as information about risks may be very limited. Finally, research during apandemic may lead people to embrace a research ethic that is more strongly focused on the common good(public health) than individual rights. This leads us to propose the following aims in an administrativesupplement that examines research on Covid19.1. Analyze qualitative (open-ended) survey data from IRB members and Covid19 researchers on how current ethical, regulatory, and institutional requirements might pose barriers to urgent Covid19 research, and what accommodations would facilitate such research. Relevant to the current R01, we will engage in text mining and model building to explore the issues arising from the need for informed consent, waivers of consent, or permissions for use of human subject data and biospecimens.2. Review findings from the survey of IRB members and Covid19 researchers to guide adaptation and expansion of the parent R01's EBCP toolkit and implementation trial. We anticipate that this will entail providing guidance on electronic informed consent processes and alternatives to legally authorized representatives when patients lack the ability to consent to research.3. Explore the policy implications of the project, and broadly disseminate data and findings. We will publish a special issue of the journal, Narrative Inquiry in Bioethics, publish our findings in peer reviewed journals, and anonymize and deposit data in the ICPSR data repository at the University of Michigan.",2020,2023,Washington University,235401,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues in Research | Research to inform ethical issues in Governance | Health leadership and governance,2018 +C06897,3UH3CA202723-05S1,Adapting KS-Detect technology to high-throughput COVID-19 screening,"Abstract: The COVID-19 pandemic represents a worldwide infectious disease challenge that disrupted our economic,educational, and social norms in a way that was largely unimaginable just months ago. At present the mostefficacious method of limiting the spread of the disease has been to test those that exhibit symptoms - typicallyby nucleic acid based viral identification methods - and isolate those that are positive. Even at this early stagethis approach has put significant strain on the diagnostic infrastructure of advanced countries, let alone thosewith fewer resources. As we move beyond symptom-initiated confirmation diagnoses to the larger scalescreening that may be required to identify asymptomatic carriers and to restart sections of our economy, muchmore rapid and higher throughput techniques will be required.Under ongoing NIH/NCI UH2/UH3 (UH3CA202723) funding we have been developing TINY (Tiny IsothermalNucleic acid quantification sYstem). The TINY system is a self-contained, portable device for the detection andLAMP-based quantification of viral nucleic acids designed for use in settings with limited resources. Through thatprogram, the system is currently deployed within Uganda for identifying Kaposi's Sarcoma Herpes Virus (KSHV)in human biopsies as a novel diagnostic technique for Kaposi's Sarcoma. The system has been validated onover 500 samples showing sensitivity and specificity of 93% and 95%.Through this supplement request, we propose to upscale the TINY system to enable much high-throughputscreening - from 6 parallel samples to 96 - and adapt it to a run a recently developed LAMP assay for SARS-CoV-2 detection which has already been validated on 182 patients in New York City. We believe that this willsimultaneously contribute to the need for higher throughout COVID-19 diagnostics and advance the NCIs desirefor platforms that can enable broader screening for viruses which are known to cause cancers (e.g. HPV in thecase of cervical cancer).",2020,2021,Cornell University,153746,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2016 +C06898,3P30AG066506-01S1,"COVID-19, Social Distancing, and Cognitive Impairment in 1Florida ADRC participants","With ~560,000 Alzheimer's disease (AD) patients and >4 million residents >65years old, Florida will continue to be, an epicenter of the AD epidemic in the UnitedStates. The 1Florida ADRC is a collaboration between Florida institutions,including the University of Florida (UF), Mt. Sinai Medical Center in Miami Beach(MSMC), University of Miami (UM), Florida International University (FIU), and FloridaAtlantic University (FAU). The 1Florida ADRC's global mission is to work with otherADRCs and AD stakeholders to change the understanding of AD and relateddementias (ADRDs) so AD+ADRDs are more quickly and accurately diagnosed, moreeffectively treated, and ultimately prevented or cured. Multiple studies suggest ahigher incidence of dementia among Hispanics and other underrepresented minoritypopulations (URM). Our successful recruitment and evaluation of a majority Hispaniccohort has enabled us to begin to evaluate whether there are differences inAD+ADRDs between Hispanics and non-Hispanics in South Florida. Enhancing ourunderstanding of dementia in ethnically and racially diverse populations is a majortheme of our ADRC. The SARS-CoV-2 or severe acute respiratory syndromecoronavirus type 2 (COVID-19) pandemic could prove especially detrimental to thehealth and well-being of individuals with cognitive impairment due to Alzheimer'sdisease and related disorders (ADRD). We believe this pandemic has placed ourclinical core cohort and indeed all families affect by AD+ADRD under a great deal ofstress. In this supplement, we will leverage our successful institutional and investigatorpartnerships to further expand our engagement and longitudinal follow up ofparticipants with ethnic, linguistic, cultural, and genetic diversity, as well ascomorbidities associated with AD (e.g., vascular disease, Lewy Body Dementia(LBD)). The specific aims of this supplement are to examine: 1) Effects of socialisolation stress as a result of COVID-19 on mood, function, behavior andcognitive status 2) Effects of cognitive impairment severity on social distancingbehaviors. 3) Extent of access and proficiency with video communicationstechnologies 4) Extent of interest in participation in a telecommunicationsdelivered supportive group program among those participants with videocommunications technology access.",2020,2025,University Of Florida,154001,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Other secondary impacts | Health service delivery,2020 +C06899,3R01LM006910-20S1,Discovering and Applying Knowledge in Clinical Databases,"PROJECT Summary: The long-term goal of our parent project, ""Discovering and applying knowledge in clinicaldatabases,"" is to learn from data in the electronic health record (EHR) and to apply thatknowledge to understand and improve health. Its first two aims are as follows: (1) Taking aknowledge engineering approach, study the effect of preprocessing and analytic choices onreducing health care process bias, and using machine learning techniques, learn more abouthealth care process bias. (2) Taking a more empirical approach, use dynamic latent factormodeling and variation inference to accommodate health care process bias, learning how apatient's health state and health processes affect censoring, exploiting information from manyvariables at once.For this supplement, we plan to focus on COVID-19. The emergence of the virus SARS-CoV-2and its corresponding disease, COVID-19, has led to about 100,000 deaths in the US and greateconomic loss and human suffering. Carrying out randomized clinical trials to assess treatmentis essential but stymied by the difficulty recruiting sufficient patients and the urgency of thequestion. Clinical databases are beginning to fill with COVID-19 patients, but the acuity andseverity of the disease make drawing causal conclusion much more difficult, resulting in aliterature filled with conflicting observational studies.We propose to employ structural causal modeling in the study of COVID-19, engaging expertisein such modeling. We will use the Columbia University Irving Medical Center's clinical datawarehouse with over 6000 testing positive for SARS-CoV-2 and the Observational Health DataScience and Informatics (OHDSI) network, which includes most COVID-19 patients in Korea,Spain, the US Veterans Administration, Stanford, Tufts, and new sites coming on board.",2020,2024,Columbia University Health Sciences,37243,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2000 +C06900,3R01AI134861-03S1,Supplement: Immunometabolic and epigenetic effects of obesity on innate immune surveillance in cancer,"Project Summary: The COVID-19 pandemic has affected millions worldwide, however it is clear that there arepredisposing factors that lead to critical illness and mortality including older age, and underlyingconditions particularly type 2 diabetes (T2DM) and obesity. The Centers for Disease Control andPrevention (CDC) has reported that patients with T2DM may have up to ten-times greater risk of deathwhen they contract COVID-19. Understanding the immune response is critical to preventing or reducingmortality from COVID-19 and informing therapeutic strategies for this patient population. The overallaim of this proposal is to identify the immune basis for increased disease severity and death fromCOVID-19 in patients with obesity and T2DM.It is now appreciated that obesity is associated with immune dysregulation, which may be the cause ofsome obesity related diseases. For example, Natural killer (NK) cells, so-called due to their naturalcytotoxicity against viruses and tumors, are unable to kill targets efficiently in obese humans and mice.We have recently found similar defects in CD8 T cells in patients with obesity and T2DM. The keyunanswered questions are 1) are these immune defects responsible for the increased severity anddeath from COVID-19 in patients with obesity and T2DM 2) do patents with obesity and T2DM have anunderactive or overactive (damaging cytokine storm) in response to COVID-19? and 3) is metabolicdysregulation at the heart of these defects? It is critical to understand the immune basis for thissusceptibility in order to prevent or reduce mortality from COVID-19 and to inform therapeutic strategiesin this patient populations. Findings from this study may lead to understanding the immune responsein patients with obesity for future novel viral outbreaks.",2020,2022,Brigham And Women'S Hospital,447500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C06901,3P50CA190991-07S1,Project 3 Supplement - A Novel Cellular Tumor Vaccine Strategy for Mutant IDH1 glioma,"Historically, stimulation of humoral immunity in the form of antibodies has been the most effective means to provide protection against most viral infections. For this reason, almost all SARS-CoV-2 vaccine efforts are focused on stimulating humoral immunity. At the same time, there is evidence to suggest that, as with other RNA viruses such as RSV and Dengue, stimulating protective humoral immune responses against SARS-CoV2 may not be feasible. The alternative, stimulating T cell immune responses to SARS-CoV-2, has been advocated as being the preferred means of inducing long term protective immunity. However, it is currently not known if T cell immunity by itself can protect against SARS-CoV-2 infection or the development of severe COVID-19. In addition, even if stimulating cellular immunity is the goal, it is not clear how this could best be achieved. Stimulating T cell responses, especially cytotoxic T cell responses, with vaccinations has proven to be difficult. We have developed a novel cellular vaccine strategy that induces very strong T cell, especially cytotoxic T cell, responses. In this strategy, circulating monocytes are purified from the blood, loaded with a target antigen, then given back by intravenous infusion. In animal models, this results in the development of much stronger T cell responses than we have been able to obtain with other vaccine strategies but no antibody responses. In the case of COVID-19, this monocyte vaccine platform provides an excellent opportunity to determine if T cell responses are sufficient to protect against SARS-CoV-2 infection or the development of severe COVID-19. In this supplement, we propose to perform critical preclinical studies that will be required by the FDA before a clinical trial of a COVID-19 monocyte vaccine can be approved. These studies include examining vaccine-induced immune responses to SARS-CoV-2 and the toxicity of monocyte vaccination in mice and demonstrating that we can formulate a human COVID-19 monocyte vaccine at a scale sufficient for a clinical trial.",2020,2024,Duke University,160934,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2014 +C06902,3R01AG057510-03S1,Brain Health and Ethnic Disparities in ADRD Risk: The Case of Arab Americans - Covid Supplement,"Project Abstract: This application for an NIA Administrative Supplement proposes to expand Alzheimer's Disease Risk andEthnic Factors: The Case of Arab Americans (R01AG057510) to incorporate an assessment of COVID-19stress as an area of investigation through an immediate, brief telephone interview. The parent study is the firstof its kind to focus on AD health disparities in Arab Americans aged 65 and over living in the metro-Detroitarea, home to the largest and most visible Arab American community in the US. Building on the original study,the planned supplement leverages an existing longitudinal study of Blacks and Whites from the samegeographic area. Capitalizing on the bilingual data collection instruments prepared and finalized for the parentnow delayed face-to-face study, we will conduct telephone interviews to address the following aims: 1)Characterize prevalence of COVID-19 stress types and cognitive health in metro-Detroit among threeracial/ethnic groups; 2) Identify aspects of social relations that buffer links between COVID-19 stress andcognitive health; and 3) Determine the role of pre-existing social resources on COVID-19 stress and cognitivehealth. This project will document the prevalence of pandemic stress and its link to cognitive health amongthese vulnerable older adults in three prominent racial/ethnic groups in Michigan. Further, the telephone modeof the proposed data collection will provide a methodological opportunity to compare modes of cognitive healthdata collection between the newly proposed and parent study (delayed due to COVID-19) among diverseracial/ethnic groups. Establishing reactions to COVID-19 and examining links to cognitive health provides aninnovative, cost effective opportunity to more fully identify health disparities. Understanding the contribution ofsocial relations will refine theory about stress and cognitive health, provide key information to better prepare forfuture pandemics and develop intervention strategies for eradication of cognitive health disparities.",2020,2023,University Of Michigan At Ann Arbor,390000,Human Populations,Black | White | Other,Older adults (65 and older),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C06903,3R01AA024760-05S1,Impact of the COVID-19 Pandemic on Alcohol Use and PTSD Symptoms in a Sample of African American Heavy Drinkers,"Project Summary/Abstract: The current global pandemic raises critically important questions about the ways that heavy drinking and alcohol usedisorder (AUD) may increase risk for COVID-19 illness and engaging in risk reduction strategies, as well as howuncertainty and stress related to the pandemic and measures to contain it may impact drinking and related outcomes.Our current NIAAA-funded study (Pharmacogenetic Treatment with Anti-Glutaminergic Agents for Comorbid PTSD &AUD; 5R01AA024760) is testing the efficacy of pregabalin in reducing symptoms of AUD and posttraumatic stressdisorder (PTSD) in a sample of mostly low socioeconomic status (SES) African American men and women who haveexperienced an array of lifetime traumatic events. Over the course of the trial, we have assessed 140 heavy drinkerswith a variety of measures of alcohol use, trauma experiences, PTSD and mood symptoms, other substance use, andgeneral functioning (i.e., taking care of oneself, communicating and interacting with others, taking care of work anddomestic responsibilities). Further examination of this highly diverse sample has the potential to shed light on theconsequences of the pandemic on high-risk community members and the ways that pandemic-related experiences ofstress, uncertainty, and social isolation may impact alcohol use and related outcomes. In response to Notice of SpecialInterest: Availability of Administrative Supplements and Competitive Revision Supplements on Coronavirus Disease2019 (COVID-19) within the Mission of NIAAA (NOT-AA-20-011), we propose to capitalize on this existing researchcohort to investigate urgent research questions of significance to the COVID-19 pandemic among an underservedpopulation of participants with comorbid alcohol use and mental health disorders. First, we will collect descriptive dataon participants' experiences of COVID-19 illness and engaging in risk reduction practices. This will include experienceswith testing, treatment, and hospitalization for COVID-19, as well as engaging in risk reduction practices such as socialdistancing and wearing masks. Second, we will explore the ways that alcohol use, PTSD symptoms, other substanceuse, mood symptoms, social support, and general functioning are related to engaging in COVID-19 risk reductionpractices. Third, we will compare alcohol use, PTSD symptoms, other substance use, mood symptoms, and generalfunctioning assessed before (prior to February 1, 2020) and after the onset of the pandemic to examine how thepandemic affected these domains. Including measures of functional outcomes offers the opportunity to explore how thepandemic has impacted participants' ability to continue to perform meaningful family and societal roles.",2020,2021,University Of Maryland Baltimore,152703,Human Populations,Black,Adults (18 and older),Unspecified,Drug users | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2016 +C06904,3P30AG031679-10S1,Defining inflammaging and monocyte dysfunction in COVID-19 disease,"Abstract: People over 65 are disproportionately burdened by coronavirus disease 2019 (COVID-19). Oder adults (i.e.,65 years old and older), more often men, experience higher disease severity and increased mortality comparedto younger individuals and women (1, 2). Notably, aging is associated with chronic low-grade inflammation(i.e., inflammaging) that can exacerbate many diseases and has been associated with reduced vaccineresponse to respiratory infections, such as influenza A virus (IAV) (4, 5). COVID-19 severity has beenobserved (6) to resemble a ""cytokine storm"" - a term first described in relation to severe IAV infection (7, 8).Because respiratory viral infections often result in the recruitment of monocytes where they can amplifyinflammatory response, a better knowledge of monocyte dysfunction would inform the development of effectivetherapeutics to reduce inflammation and improve vaccine responsiveness. A critical age-related dysregulationobserved in response to IAV infection (that we speculate may be relevant to SARS-CoV2 infection) is theprofound dysregulation in monocyte response. Notably, peripheral blood monocytes isolated from olderindividuals when compared to monocytes from younger individuals have an amplified inflammatory response(e.g., upregulated NF-kB pathway) and a profound deficit in antiviral interferon response (e.g., type I and IIinterferons, interferon stimulated genes).We have access to a unique cohort through collaborative linkage with Italian investigators at the University ofModena and Emilio Reggio and the Modena COVID-19 working group that includes samples from 167 SARS-CoV2 infected men and women that were hospitalized with COVID-19. The age range of the men and womenis 30-90 years old. We hypothesize that a focus on interferon, proinflammatory, metabolic and senescencepathways will provide proteomic signatures that distinguish disease outcomes. Our primary objective in thissupplement is to characterize inflammatory signatures in serum and primary monocytes in COVID-19disease, controlling for age and biological sex. We will characterize serum circulating proteomes andprimary monocyte proteomes using banked serum and primary monocytes from uninfected (n=20), SARS-CoV2 positive adults hospitalized then discharged (n=20) and SARS-CoV2 positive adults that are deceased(n=20). Serum and cellular proteomic signatures will be used to evaluate type I-III interferons, pro/anti-inflammatory pathway, metabolic pathways and immunosenescence (e.g., senescence associated secretoryphenotype: SASP).",2020,2021,Brigham And Women'S Hospital,366578,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2008 +C06905,3DP5OD026429-03S1,The Health Consequences of Urban Scaling,"PROJECT Summary: The COVID-19 pandemic has killed more than 100,000 people in the US, where very wide inequities in COVID-19 outcomes have been reported for racial/ethnic minorities, including Hispanics. Hispanics suffer from specificsocial vulnerabilities that lead to increased risk of infection, and increased prevalence specific risk factors thatlead to increased risk of severe illness. However, the number of confirmed cases in Hispanics may be severelyunderestimated due to differential coverage of testing by area and population group. Moreover, most preliminarymeasures of inequities in mortality have ignored the role of the different age structure of racial/ethnic groups.Creating consistent estimates of racial/ethnic inequities in COVID-19 outcomes is therefore key to exploringtrends and predictors of these inequities, as a first step to improve the targeting of future interventions.Concurrently, several non-pharmaceutical interventions (NPI) have been deployed to control the pandemic, Thecapacity of racial/ethnic minorities to adhere to or benefit from (NPI) has been limited by several structuralbarriers, including deficient social safety nets, a lower possibility of teleworking and a higher likelihood of workingin essential occupations. Overall, these structural constraints make isolation more challenging and increase thelikelihood of exposure to infection even in areas with social distancing. Continued viral transmission in specificpopulation subgroups makes the control of the pandemic more challenging for the entire population, and theemergence of future waves more likely. In summary, Hispanics are one of the racial/ethnic groups most impactedby the pandemic and, concurrently, one of the groups least able to benefit from NPI. For the current and futurewaves of the pandemic, it is imperative to reduce the risk of infection across the population to reduce communitytransmission; therefore. Therefore, understanding where and why health inequities are wider and whether NPIwork across different groups is key to preventing future waves by reducing overall levels communitytransmission. We propose to systematically examine trends and predictors of heterogeneities of health inequitiesin COVID-19 outcomes between Hispanics and non-Hispanic whites (NHW), and between the neighborhoodswhere they predominantly live, across and within US cities, and the potential unequal effect of NPI in Hispanicsvs NHW. We will leverage data on COVID-19 outcomes by race/ethnicity and neighborhood from the 30 largestcities of the US, corrected for imperfect testing quality and coverage; (2) social inequality measures; and (3) adiverse set of compilations of state-, county- and city-level policies. By using a heterogeneous sample of cities,we will uncover inequities and predictors of these inequities that will allow for more specific targeting ofinterventions that may prove key in continuing to control current waves of the pandemic and to prevent futurewaves. We will also demonstrate whether NPI may be less effective in Hispanics or predominantly Hispanicneighborhoods. Since NPI remain the most effective tool for epidemic control, their failure on specific populationsubgroups represents a hazard for the entire population.Drexel Internal Data",2020,2021,Drexel University,377709,Human Populations,White | Other,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C06906,3R21AG061365-02S1,"COVID-19, Social Distancing and Spouse/Partner Caregiving for those with Alzheimer's Disease","Project Summary: This administrative supplement extends a qualitative study of same-sex and heterosexual olderadults who care for their spouses/partners with Alzheimer's disease and related dementias. Theoriginal research seeks to pinpoint how caregivers draw upon existing gender repertoires - setsof skills and resources learned over the life course that affirm gender identities formed inrelation to the gender division of labor-in performing their care work. The resulting caregivingapproaches influence the particular areas of care work that these caregivers find problematic,the ways they might respond to these challenges, and the extent to which such strategies helpcaregivers effectively perform their work. This study asks how sexual orientation shapes genderrepertories, given that the division of labor among gay and lesbian couples must be negotiated,and examines how this shapes caregiving approaches and experiences.The emergence of COVID-19 and such containment measures as social distancing havecreated a situation with which all AD caregivers must contend, regardless of gender or sexualorientation; however, the ways in which they do so likely exhibit some differences. Thisadministrative supplement builds upon the parent study and seeks to explore the impact ofCOVID-19 and social distancing across time and caregiving groups. The proposedsupplemental study will involve re-interviewing previous respondents from the parent study toidentify similarities and differences in terms of what caregivers find challenging, and thestrategies they use to deal with these difficulties. Understanding the ways that COVID-19 andsocial distancing shape these caregiving experiences will provide much needed information oncaregiving performed by LG and heterosexual spouses/partners while also revealing howgender and sexual orientation shape what caregivers perceive to be challenging, the strategiesthey use to cope with these, and the resources they have available to them. Knowledge gainedfrom the study will have implications for both policy-makers and practitioners who seek todevelop effective interventions to support caregivers and prevent negative physical and mentalhealth outcomes.",2020,2021,Virginia Tech,214433,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C06907,3R01AG066707-01S1,Endophenotype Network-based Approaches to Prediction and Population-based Validation of in Silico Drug Repurposing for Alzheimer's Disease,"There have been more than 550,000 confirmed cases and over 22,000 deaths for COVID-19, the disease causedby the virus SARS-CoV-2, in the United States. Older individuals have the declined immune systems and ahigher mortality from COVID-19; furthermore, there are currently no effective antiviral medications againstCOVID-19. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, offersemerging prevention and treatment strategies for COVID-19. SARS-CoV-2 requires host cellular factors forsuccessful replication during infection. Targeting virus-host protein-protein interactions (PPIs) offers an effectiveway for the development of drug repurposing (i.e., hydroxychloroquine (HCQ), melatonin, and indomethacin)for COVID-19 as demonstrated in our recent study (Cell Discovery 2020). Supported by the NIA R01, our teamare developing and implementing innovative network medicine and systems biology methodologies for drugrepurposing and drug combinations. We showed that HCQ was associated with a decreased risk of coronaryartery disease by reducing the expression of VCAM1 and IL-1β in human aortic endothelial cells. Exogenousmelatonin administration may be of particular benefit to COVID-19 older patients given an aging-related reductionof endogenous melatonin levels. Therefore, the central unifying hypothesis of this project is that an integrative,network medicine methodology that quantifies the interplay between the virus-host interactome and drugtargets in the human interactome network will offer highly repurposable drugs and clinically relevant combinationregimens for effective treatment of COVID-19. Aim 1 will test disease module hypothesis for prediction andvalidation of repurposable drugs for effective treatment of older individuals with COVID-19. We will utilize anetwork-based knowledge graph approach that incorporates not only virus-host interactions from SARS-CoV-2,but also public drug-target databases, the human protein-protein interactome, along with 24 millions ofpublications from PubMed database. Aim 2 will test the hypothesis that combining anti-inflammatory and antiviraltherapeutics for effective treatment of the underlying pulmonary and cardiovascular conditions in older individualswith COVID-19. We will utilize state-of-the-art pharmacoepidemiologic analyses to validate the clinical efficiencyof drug combinations (i.e., melatonin plus HCQ) in reducing incidence of pulmonary and cardiovascularconditions (including acute respiratory distress syndrome, pneumonia and lung injury) in older individuals, usinglarge-scale longitudinal Claims-Electronic Medical Record (EHR) patient databases, along with in vitroobservations in human aortic endothelial cell and pulmonary arterial endothelial cell models. To reduce theconfounding factors from patient databases, we will perform time-to-event pharmacoepidemiologic outcomeanalyses using large-scale de-identified patient EHRs from the Cleveland Clinic COVID-19 registry database.The successful completion of this project will offer clinically relevant repurposable drugs and combinationregimens for COVID-19 patients with aging-related pulmonary and cardiovascular conditions.1",2020,2024,Cleveland Clinic Lerner Com-Cwru,395914,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C06908,3U01AT009974-03S1,Optimizing a self-directed mobile mindfulness intervention for improving,"Abstract The novel coronavirus (COVID-19) pandemic has changed access to and the delivery of medical care across the world rapidly and radically as increasingly large waves of patients fill clinics, hospital wards, and intensive care units (ICUs). Patients with comparable illnesses have high rates of persistent psychological distress symptoms including depression, anxiety, and PTSD. Currently there are few easily accessible therapies available for this distress in this time of deep fear and worry, 'social distancing,' cancelled clinics, isolation and quarantine practices, and understaffed hospitals. Lift, our novel mobile app-based mindfulness intervention, can address COVID patients' distress and access to care issues. Lift was piloted successfully in the intensive care unit (ICU) and has shown the greatest impact on symptoms of any ICU-based trial conducted to date (R34 AT00819). Lift is currently in the midst of a multicenter factorial experimental clinical trial designed to determine which of 8 versions is optimized for symptom relief, cost, and scalability (parent U01 AT009974). This Supplement seeks to expand the scope of the parent U01 project to do what has never to our knowledge has been attempted: test the clinical impact of an automated psychological distress intervention rapidly deployed during a pandemic. To address this unique clinical gap, we propose a 1-year supplemental project involving an additional 300 cardiorespiratory failure survivors of COVID-19 with three specific aims: (1) Compare the clinical impact of two automated, self-directed programs delivered through an identical mobile app platform including Lift (High dose / App Response to Symptoms / Intro call by staff) vs. a validated education control and (2) Compare long-term (6-month) outcomes of COVID RCT patients both by treatment arm as well to the entire CORAL COVID cohort, and (3) Explore barriers and facilitators to intervention deployment, uptake, and engagement in a pandemic. This pragmatic randomized clinical trial will be nested within the NIH PETAL network's CORAL COVID trials. Innovative elements of our supplement proposal include its paradigm-shifting rapid deployment strategy that requires no direct patient contact; automated features (electronic consent, symptom screening, data collection, content directed to change in symptoms); the unique population and pandemic setting; and easily disseminatable mobile app delivery system. The extensive reach of the PETAL network and its sites' numerous COVID positive patients are ideal for testing an intervention that could advance the field with a personalized, yet broadly scalable therapy. To our knowledge, this would be the first mind-body intervention rapidly deployed in a pandemic. As such, the lessons learned could help to guide future interventions that can be quickly scaled to meet surge demands in times of local, regional, or national crisis.",2020,2023,Duke University,670404,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2018 +C06909,3DP5OD023118-05S1,Antibody display libraries for precision screening of antibody immune responses to SARS-CoV-2,"PROJECT SUMMARY/ABSTRACT This project will determine the antibody-based immune features in COVID-19 patients to accelerate thedevelopment of new medical interventions. SARS-CoV-2 causes asymptomatic or mild disease in manyindividuals, demonstrating that an effective human immune response can fully prevent disease. However, itremains unclear what immune response features are associated with protection from disease. To address thisquestion, here we will analyze comprehensive antibody immune responses in COVID-19 patients and determinehow the molecular features of antibody immunity correlate with COVID-19 symptom severity. First, we will immortalize antibody immune libraries from COVID-19 patient cohorts into yeast display librariesfor comprehensive in vitro functional screening. B cell samples from COVID-19 patients will be isolated andemulsified as single cells for native antibody DNA recovery, and antibody genes will be transformed into a yeastFab display platform for repertoire-scale antibody functional analyses. Antibodies will be screened for binding tothe SARS-CoV-2 spike trimer, a dominant neutralization target, and also for inhibition of ACE2 binding to mapneutralizing antibodies in human immune responses. We will also mine our renewable antibody immune libraries for broader features that may correlate withCOVID-19 disease severity. We will investigate antibodies targeting broad SARS-CoV-2 antigens and epitopes,including multiple epitopes on the spike trimer protein (such as the receptor binding domain, RBD, the N terminaldomain, NTD, and the S1 region) and internal viral proteins (e.g., nucleocapsid protein). We will also map themolecular features of single B cell responses (e.g. affinity, competition-based epitope mapping, and differentialbinding to different spike protein conformations) to comprehensively track anti-SARS-CoV-2 molecular immunityin a human cohort. We will analyze the genetic features of each antibody clone to help elucidate the balance ofneutralizing vs. non-neutralizing antibodies as potential disease correlates. Finally, we will perform large-scale data mining of the antibody repertoires from each patient population toidentify key molecular features that may distinguish mild and severe SARS-CoV-2 infections. These newmolecular-scale correlates and potential biomarkers will improve basic and clinical understanding to advanceCOVID-19 preventions and therapies. We seek to reveal critical immune-based biomarkers of COVID-19diseases severity and identify new potent antibody drug candidates to treat and prevent COVID-19.",2020,2021,University Of Kansas Lawrence,376544,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C06910,3R01EB027202-01A1S1,Directed evolution of polymerases that can read and write extremely long sequences,"Supplemental Project Summary (derived from the original, changes underlined)Advances in synthetic biology have accelerated to the point where the synthesis of entire genomes is nowpossible. However, the technologies for these feats are painstaking, and the production of a new chromosomeor genome requires multiple years of effort, working from small fragments to ever larger assemblies. The speed(and ultimately scale) of large fragment assembly would be greatly improved if it were possible to routinelyamplify very long stretches of DNA (> 100 kb) in vitro. The methods developed in the execution of this proposalshould also prove extremely useful for greatly improved reagents for molecular diagnostics for SARS-CoV-2. Tothat end, this proposal is focused on the further development of a novel directed evolution method known asCompartmentalized Self-Replication (CSR), in which polymerases expressed in cells in emulsions undergothermal cycling to amplify their own genes, to generate long read DNA polymerases that should prove capableof generating PCR amplicons > 100 kb in length, with few errors. To achieve this goal, we propose to develop anovel library construction method that most efficiently brings together sequence and structural domains from avariety of DNA polymerase variants to form diverse chimeras (Aim 1.1), and to sieve these libraries usingimprovements to CSR that will allow us to select for extreme processivity in yeast (Aim 1.2) and efficient error-correction (Aim 1.3). Using the methods in Aim 1.2, we can produce polymerase variants that should be able todirectly participate in RT-qPCR without sample preparation, including from samples inactivated with denaturants.The variants that result will be characterized for their ability to synthesize long amplicons in vitro (Aim 2.1), fortheir fidelity (Aim 2.2), and for their detailed kinetic properties (Aim 2.3). Finally, to better ensure the processivityof the resultant polymerase chimeras, we will append either DNA-binding domains (Aim 3.1) or clamps (Aim3.2) that should lead to much better ability to grip DNA. Using the methods described in Aim 3.1, we can generatethermostable reverse transcriptases that should prove useful for the development of isothermal amplificationassays that can be used at point-of-care, or in resource-poor settings. In addition to accelerating the ongoingrevolution in genome synthesis, such long-read polymerases should also pave the way to new sequencingtechnologies, including for single molecule sequencing and for single cell sequencing. In the current crisis,polymerase engineering for particular functions, directed towards needs that the community has and that needto be resolved for forward motion on testing, is a critical component of a national plan.",2020,2021,"University Of Texas, Austin",182969,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C06911,3R01AG058639-02S2,BRAIN-2 COVID-19 Administrative Supplement (2),"The NIA-funded BRAIN-ICU-2 Study [Bringing to light the Risk factors And Incidence of Neuropsychologicaldysfunction (dementia) in ICU Survivors, 2nd Study] will define the relationship between ICU delirium anddementia. The proposed administrative supplement to BRAIN-ICU-2 Study (R01 AG58639) is in response toNIA Availability of Administrative Supplements and Revision Supplements on Coronavirus Disease 2019(COVID-19) (NOT-AG-022; PA-18-591). To understand the brain tissue damage of acute delirium caused bySevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), we will perform new neuropathologicalstudies of critically ill patients affected by COVID-19, as well as those with Alzheimer's disease and relateddementia (ADRD) with/without critical illness. By studying COVID-19, we will better understand the relationshipbetween delirium and ADRD. During the current COVID-19 pandemic, intensive care units (ICU's) across thenation are awash with patients experiencing delirium, a major ICU risk factor for future ADRD. These deliriumsymptoms of impaired consciousness include headache, alteration of gustatory, olfactory, and visual function,neuropathy, seizures, agitation, encephalitis, and/or Guillain-Barre syndrome. These delirium signs andsymptoms could be due to SARS-CoV-2 infection of the brain, particularly in those with ADRD. We do notknow if there are direct nervous system consequences of COVID-19 (e.g., inflammation), and/or indirectnervous system consequences, e.g., coagulopathy. To our knowledge, limited autopsy series that includedbrain tissue have been published. No information about ADRD was provided. The proposed supplement willspecifically compare multiple groups of patients, ICU patients with/without ADRD with/without COVID-19, alongwith non-ICU patients with/without ADRD and with/without COVID-19. The BRAIN-ICU-2 study will provide ICUpatients with/without ADRD with/without COVID-19. The NIA-supported Religious Orders Study (ROS; P30AG10161, R01 AG15819), and Rush Memory and Aging Project (MAP; R01 AG17917) will provide non-ICUpatients with/without ADRD and with/without COVID-19. The proposed supplement will further build oncollaboration between the Vanderbilt and Rush BRAIN-ICU-2 study teams, and represent the mostcomprehensive neuropathologic examination of COVID-19 brains compared to non-COVID-19 brains, in thosewith/without ADRD, and with/without critical illness. This supplement will create a unique resource for theworld-wide COVID-19 research community, with a strong and sustained impact on the fields of ICU deliriumand ADRD.",2020,2024,Vanderbilt University Medical Center,868245,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2019 +C06912,3R01AG028082-12S1,Mechanisms of dysregulated immunity with aging,"PROJECT SUMMARY/ABSTRACTSince our competitive renewal was funded last year, a global pandemic of a novel coronavirus has emergedthat has resulted in higher number of deaths than prior coronavirus outbreaks (e.g., SARS, MERS). Inparticular, older patients (i.e., > 60 years old) exhibit markedly increased mortality from COVID-19 (SARS-CoV2) infections. Hence, we urgently need to understand why older people exhibit worse outcomes during COVID-19 infection. Based upon our preliminary data in mice employed in the parent R01, we hypothesize that duringCOVID-19 infection with aging, senescent alveolar epithelial cells (AEC) secrete neutrophil-attractingchemokines to induce neutrophil recruitment into the lung as well as PGE2, a pleiotropic lipid mediator, whichsuppresses alveolar macrophage proliferation and function. As alveolar macrophages are key in clearingdebris and resolving inflammation, we postulate that impairments in alveolar macrophages with aging inhibitinflammation resolution during influenza infection. In Aim 1, we will leverage the human AEC culture describedin the parent R01, to understand how aging impacts the inflammatory response to SARS-CoV2 infection inAEC and how this impacts neutrophil and alveolar macrophage. In Aim 2, we will leverage, through ourcollaborators, ongoing screens of repurposed FDA agents and novel anti-microbial peptides to identify noveltherapeutics to mitigate the effects of SARS-CoV2 infection in AECs with aging. This administrativesupplement is a natural extension of our funded NIA project on aging and the innate immune response toinfluenza, and could provide urgently needed insights to the mechanisms by which aging promotes mortality toCOVID-19 and potential therapeutics to reduce the suffering and death of older people with COVID 19.",2020,2024,University Of Michigan At Ann Arbor,249600,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis | Prophylactic use of treatments,2007 +C06913,3R01AG059752-03S1,Role of inflammasomes in Alzheimer's Disease,"PROJECT ABSTRACTSupplement to R01 AG059752-03:Neuroinflammation is an important component of Alzheimer's disease (AD) and Fronto-temporal dementia(FTD). However, the molecular mechanism by which inflammation modulates AD and FTD progression are notdefined. We discovered that both AD and FTD patients uniformly have evidence of activated inflammasomes intheir brains. We have also found that systemic inflammation promotes AD disease and increases thedeposition of Ab plaques, in part by reducing microglial clearance of Aβ in the brain. This process wasdependent on inflammasomes, as NLRP3 KO mice showed clear protection with nearly normalized microglialmorphology and Aβ clearance. We have also noted that NLRP3 inflammasome activation drives tau pathologyby inducing tau hyper-phosphorylation. Taken together, these observations suggest that systemicinflammation likely contributes to neurologic diseases, particularly AD and FTD, by promoting the accumulationof Ab plaques and inducing the phosphorylation and aggregation of tau in neurofibrillary tangles.Acute COVID-19 is associated with a hyper-inflammatory cytokine storm and more than a third of patientsdevelop neurologic symptoms. We believe that acute COVID-19 driven inflammation will aggravate pre-existing neurologic disorders, such as Alzheimer's Disease (AD) and fronto-temporal dementia (FTD) viaactivation NLRP3 inflammasomes and downstream inflammasome-dependent cytokines in the brain.Successful completion of this supplemental Aims will elucidate the role of inflammasome-generated cytokinesin COVID-19 associated neurologic symptoms and could result in novel translational approaches designed tospecifically halt the inflammation that drives neuroinflammation in this disease. We also hypothesize thatCOVID-19 inflammation can potentially accelerate cognitive decline in AD and FTD patients. This study hasthe potential to identify therapeutic targets to prevent the neurologic disorders that occur in many COVID-19hospitalized patients and to determine the impact of COVID-19 inflammation on AD and FTD pathology anddisease progression.",2020,2023,University of Massachusetts Chan Medical School,280148,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2018 +C06915,3R01AG061937-03S1,Sequelae of SARS-CoV-2 Infection in Alzheimer's Disease,"Project Summary/Abstract: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemichas created a healthcare crisis that was previously reserved for the accelerating Alzheimer'sdisease (AD) diagnoses. Geriatric individuals are a high risk group prone to severe infection anddeath, however, a large percentage of these individuals will survive. The predilection of SARS-CoV-2 and AD to this population indicates age-associated factors may become aggravated uponviral infection, thereby exacerbating underlying AD symptomatology. We need a betterunderstanding of the long-term effects of SARS-CoV-2 infection - particularly in relation to ADprogression.AD is an age-related neurodegenerative disorder characterized by progressive anterogradeamnesia and eventual death. Blood brain barrier (BBB) disruption is typically observed in ADpatients leading to increased vascular permeability. This disrupted microvasculature predisposesindividuals with mild cognitive impairment and AD to increased CNS infiltration by SARS-CoV-2.Once in the CNS, SARS-CoV-2 can infiltrate host cellular components through interaction withangiotensin converting enzyme-2 (ACE2). ACE2 is part of the renin-angiotensin system,expressed on hippocampal neurons, and involved with learning and memory. Downregulation ofACE2 is observed in AD patients in conjunction with elevated amyloid-β (Aβ) and tau levels.Further internalization of this receptor upon SARS-CoV-2 neurotropism may exacerbate ADpathology and potentiate disease progression. Viral infection can also cause host cell senescenceas a defense mechanism against viral replication. The subsequent senescence-associatedsecretory phenotype (SASP) can secrete pro-inflammatory cytokines and chemokines impactingneighboring cells and causing a deleterious feed-forward cycle propagating AD pathology andcognitive decline.The Aims of our current funding mechanism are designed to elucidate the role of cellularsenescence in AD. The SARS-CoV-2 emergent crisis coupled with its proclivity to infect geriatricpopulations and our scientific understanding of viral infection on senescent cell burden providesSCIENTIFIC PREMISE for the proposed studies. For this administrative supplement wehypothesize that CNS infection of SARS-CoV-2 increases senescent cell burden thus aggravatingthe development, progression, and severity of cognitive deficits in AD mouse models.Complimentary in vitro (AIM 1) and in vivo (AIM 2) assays will be used to probe the long-termconsequences of SARS-CoV-2 infection on senescent cell accumulation andneuroinflammation,thereby accelerating cognitive and physical AD symptomatology.",2020,2021,Southern Illinois University Sch Of Med,368750,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2018 +C06916,3R01AG059823-02S1,Supplement to Lifecourse Patterns of Abuse and Elder Mistreatment (1R01AG059823-01),"In this supplement, we propose to conduct 50 qualitative interviews with adult participants of alongitudinal study on lifecourse patterns of abuse and elder mistreatment. These 60-minuteinterviews, conducted by telephone or videoconference, will consist of a short structured survey,followed by a series of open-ended questions pertaining to COVID-19 pandemic. We areparticularly interested in the effects of state-specific orders of social distancing and self-isolationrelated to the pandemic on adult child-older parent relationships, particularly when participantsare providing support and care for vulnerable older adults, and the mental health, substanceuse, and resilience of adult children. Research questions broaden the data collection on ourparent project to capture dimensions unique to the pandemic but objectives remain within theoriginal scope of the parent study. The specific aims for this application are to (1) identify theunique challenges faced by adult children of formerly abusive parents within the context ofCOVID-19 shelter-in-place orders and social distancing mandates and (2) discern personalbehaviors and social factors associated with the pandemic that influence resilience in adultswho were abused. The research is guided by a life course perspective, which provides afoundation from which to assess responses to this major life stressor in relationship to theintergenerational transmission of violence.",2020,2021,University Of Michigan At Ann Arbor,119868,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C06917,3P01AG031720-08S1,"Social Isolation and Loneliness due to COVID-19: Effect on Cognitive, Physical, and Mental Health in Older Adults in the SAGES Study","PROJECT SUMMARY/ABSTRACTWith the arrival of the SARS-CoV-2 virus and associated Coronavirus Disease 19 (COVID-19) to the U.S. inMarch 2020 came an extraordinary shift in daily living. Social distancing (SD) and sheltering in place (SIP),while essential in the fight against COVID-19, have created unique challenges for the health and well-being ofolder adults, and in particular those with mild cognitive impairment (MCI) and Alzheimer's disease and relateddementia (ADRD). Decreased socialization for many community-dwelling older adults has led to increasedfeelings of isolation and loneliness, both of which has been shown in numerous studies to lead to adverseoutcomes. For this supplement application, ""Social Isolation and Loneliness due to COVID-19: Effect onCognitive, Physical, and Mental Health in Older Adults in the SAGES Study, we propose two related sub-projects: Sub-Project 1 will examine the effects of COVID-19 related loneliness on cognitive, physical, andmental health in the Successful Aging After Elective Surgery (SAGES I) Study (NIA grant P01 AG031720, PIInouye), an ongoing prospective cohort study of 315 older adults with an average age of 84 years old, whohave been followed after elective major non-cardiac surgery with serial cognitive, physical and functionalmeasures. We will use this well-characterized cohort to (1) Examine potential predictors of loneliness resultingfrom social distancing, (2) Examine the effect of loneliness on cognitive function in persons with and withoutMCI or ADRD, and (3) Examine the effect of loneliness on physical and mental health in persons with andwithout MCI or ADRD. We hypothesize that the SIP order due to the SARS-CoV-2 pandemic will increaseloneliness in older adults, and for those with pre-existing MCI and ADRD, loneliness will be associated withgreater declines in cognitive, physical and mental health compared to those without MCI and ADRD. Inaddition to their established annual visit, all SAGES follow-up participants will undergo extra telephoneinterviews for this project, two at the start of the study and two 6 months later. The interview will includemeasures of loneliness, social network size, social and physical activities, technology use, pre-existingcognitive and functional or mobility impairment, cognition, anxiety, depression, and COVID-19 infection orexposure. Hospitalizations, medical visits, falls, nursing home placement, new prescription medication use, anddeath will be determined. Sub-Project 2 will allow us to convert study procedures to remote assessmentsduring the time of COVID-19; and to harmonize and validate the SAGES neuropsychological assessmentadministered via telephone, videoconferencing, and in-person modes. This study will generate statisticallycomparable scores across our approaches to examine cognitive trajectories over time. Significance: This studywill allow us to evaluate the effect of COVID-19 related loneliness on cognitive, physical, and mental health inolder adults and in those with MCI or ADRD. Moreover, this study will allow us to adapt our study proceduresto remote during COVID-19 and to cross-validate our remote assessment with phone and in-person modes.",2020,2023,Hebrew Rehabilitation Center For Aged,520674,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C06918,3UL1TR003015-02S5,Convalescent Immune Plasma for the Treatment of COVID-19: Mechanisms Underlying the Host Immunologic and Virologic Response,"Abstract: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), isan unprecedented global event which has required rapid adaptation to changing clinical and epidemiologicalcircumstances. There are currently limited treatment options available for COVID-19, with an estimated fatalityrate of around 4% globally, and as high as 20-50% among hospitalized populations. Convalescent immuneplasma (CIP) is a promising potential treatment for a wide range of infectious diseases, and one which can bemobilized rapidly even within the confines of resource limitations in the pandemic setting. Prior studies in otherviral pandemics and early evidence from COVID-19 suggests that it may be effective, but formal prospectivestudies of CIP in COVID-19 are lacking. This project is a multidisciplinary collaborative effort frominfectious disease (Dr. Tania Thomas, MD, MPH), pulmonary and critical care (Dr. Jeffrey Sturek, MD, PhD),and cell therapy (Dr. Lawrence Lum, MD, DSc): a phase 2 clinical trial evaluating the efficacy of CIP in COVID-19 infection. The epidemiology in this largely rural catchment area projects continued enrollment through 2020-2021 fueled by subpopulations with rapid upswing in incidence, particularly in the latinx community (one of ourspecial populations for clinical research) where our health system has focused outreach and support. Thecentral hypothesis of this proposal is that early infusion of CIP with high titer anti-SARS-CoV-2 antibodies inhospitalized patients with COVID-19 respiratory disease will prevent progression to critical illness and deaththrough modulation of the anti-SARS-CoV-2 host immune response. This will be tested through three specificaims: Aim 1) Test the effect of high titer CIP on progression to critical illness and death in moderately illhospitalized patients with COVID-19 respiratory disease; Aim 2) Determine the effects of CIP on the hostimmune response. Blood will be collected at 0 (prior to CIP infusion), 7, 14, and 28 days after CIP infusion. Acomprehensive immunologic assessment will be performed, including high-dimensional immunophenotypingby mass cytometry, single-cell RNA sequencing, as well as functional in vitro secretion assays. These will becompared to un-treated controls. Statistical modeling will be used to test associations with clinical outcome;Aim 3) Utilize subgenomic messenger RNA analysis to map the course of virologic clearance in COVID-19disease. Subjects will be tested for viral clearance by serial nasal swab to inform duration of viral viability andimplementation of social isolation practices critical for return to settings where distancing/isolation are limited.Completion of this study will help answer a critical question about the effect of CIP on critical illness and deathin COVID-19. Importantly the in-depth follow on immunologic and virologic studies will lead to a betterunderstanding of the mechanisms of progression to critical illness with the potential for targeted immune-mediated therapeutics and a diagnostic assay for viral viability that could immediately inform clinical care.",2020,2021,University Of Virginia,483575,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C06919,3R01CA203856-05S2,Care Coordination for Complex Cancer Survivors in an Integrated Safety-Net System,"PROJECT SUMMARY/Abstract: The COVID-19 pandemic presents a new and significant health threat for cancer survivors. Cancer survivorsare often immuno-compromised from cancer treatment and thus may have higher risks of contracting COVID-19 in addition to adverse outcomes related to cancer. Early findings among COVID patients show thatindividuals with a history of cancer have a higher risk of severe events that resulted in admittance to theintensive care unit, ventilation support, or premature death. COVID-19 also disproportionately affectsvulnerable, underserved, and ethnic minority populations; many of these receive their health care at safety-nethealth systems such as Parkland. Those who are African American and Latino or who are uninsured are alsomore likely to have underlying medical conditions such as diabetes, heart conditions, asthma, severe obesity,liver disease. In addition to increased risk of COVID-19 infection, cancer patients may also be experiencingdisruptions and changes to their clinical care routines due to COVID-19 shutdown and work-from-homeorders; survivors may experience delays in cancer treatment and follow-up care. Thus, racial/ethnic minorityand underserved cancer survivors who also have co-occurring chronic conditions represent the 'perfect storm'of risk factors for significant impacts on health outcomes as well as increasing health disparities.With this supplement, we will examine the impact of COVID-19 on care for vulnerable cancer survivors withhigh clinical risk further exacerbated by multiple chronic conditions, who are predominantly racial/ethnicminorities, uninsured, and served by a safety-net health system. Our specific aims are:Aim 1: Assess the impact of COVID-19 on the overall health and wellbeing of cancer survivors. Using amixed-methods approach (patient surveys and semi-structured interviews), we will assess the COVID-19effect on patients' physical, emotional, and mental health, financial impact, and coping.Aim 2: Assess the impact of COVID-19 on cancer survivors' access to cancer and non-cancer treatment andhealthcare utilization. We will capture how the pandemic impacted the delivery of cancer care and otherhealthcare services in this integrated safety-net system. We will examine whether there were treatment delaysrelated to cancer or other co-morbidities, challenges accessing care during this time, and the quality of caredelivered. Additionally, we will document and quantify the nature of COVID-19 encounters among our cohortof complex cancer survivors, using electronic health record (EHR) data extraction and analysis.These aims directly leverage existing research methods from the parent R01, adding new covariates andpatient-reported data specific to the COVID-19 experience. Given that COVID-19 has changed the caredelivery process and there is an expectation of other cycles of the disease, our findings will guide stakeholdersin the development of new and alternative care strategies that may mitigate impact among vulnerable,complex cancer survivors.",2020,2021,Ut Southwestern Medical Center,176438,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2016 +C06920,3P30CA015704-45S3,CCSG Supplement: Impact of COVID-19 on Cancer-related Health Behaviors in Rural Cancer Patients and Cancer Survivors.,"The COVID-19 global pandemic has had an unprecedented impact on the lives of almost everyresident of the United States. The subsequent public health mitigation strategies, includingsocial distancing measures, are effectively reducing transmission of the COVID-19 virus, butmay have negative impact on behaviors important for cancer patients and cancer survivors (e.g.adhering to cancer treatment or cancer surveillance, physical activity, healthy diet, or alcoholconsumption). Because rural cancer patients and rural cancer survivors already have significantbarriers to accessing cancer care and engaging in healthy behaviors, the impact of COVID-19social distancing measures may be even more pronounced in these settings. The purpose ofthis study is to conduct a cross-sectional survey of 800 (400 rural, 400 non-rural) cancerpatients and cancer survivors to measure non-adherence to cancer care. We will also explorethe degree to which COVID-19 social distancing measures are associated with non-adherence tocancer care and unhealthy cancer-related health behaviors for rural and non-rural participants.Survey items will be drawn from core items developed by a collaboration with more than 15other NCI-funded Cancer Centers (University of Alabama Coordinating Center) studying theimpact of COVID-19 on health behaviors in various settings and populations. Additional itemsto identify cancer patients and survivors will be drawn from the literature or developed basedon the Health Belief Model, informing overall survey development. We will compareproportions of cancer patients who report non-adherence to cancer care (either missed ordelayed cancer treatment or surveillance) in rural and non-rural settings using the four categoryRural Urban Community Access (RUCA) classification based on zip code. Our unique reachacross Washington State, which includes significant Hispanic/Latino populations in ruralcommunities, and focus exclusively on cancer patients and cancer survivors, is an essentialcontribution to this larger effort. The results of this study will be critical in helping understandthe potentially negative health impact of COVID-19 for rural cancer patients (a particularlyvulnerable group) and provide guidance to public health professionals and policy makers todevelop strategies to reduce the negative health impact.",2020,2020,Fred Hutchinson Cancer Research Center,176324,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C06921,3R61AT010799-01S1,"Understanding the Impact of COVID-19 on Methadone Treatment Retention and Adherence in an Underserved, Minority Population with OUD","PROJECT Summary: The opioid use disorder (OUD) crisis in the US is an epidemic of poor access to care, including medication foropioid use disorder (MOUD) and evidence-based behavioral interventions to support MOUD outcomes. Low-income, racial/ethnic minority individuals with OUD disproportionately evidence poor MOUD outcomes,including less than half of individuals typically being retained in MOUD at six months. Retention is one of thefactors most predictive of future relapse, functioning, and mortality. Implementing evidence-based interventionsto improve MOUD retention that are particularly appropriate for the needs of low-income, racial/ethnic minorityindividuals with OUD is essential. Peer recovery coaches (PRCs), trained individuals with their own livedexperience with substance use disorder, may be uniquely suited to address common barriers to MOUDretention among underserved populations, including stigma, challenges navigating services, housing instability,other structural and psychosocial factors. PRC-delivered interventions are a promising strategy for improvingMOUD retention for low-income, minority individuals with OUD, yet there are few evidence-based interventions(EBIs) that have been evaluated for PRC delivery to promote MOUD retention. Preliminary work by our teamsuggests that behavioral activation (BA) may be a feasible, scalable reinforcement-based approach forimproving MOUD retention for low-income, minority individuals with OUD by PRCs. The proposed study buildsupon our team's formative work to adapt and evaluate the effectiveness and implementation of a PRC-deliveredBA intervention (Peer Activate) to support MOUD retention for low-income, minority individuals initiating MOUD inBaltimore City, which has one of the highest overdose-fatality rates in the US and greatest burdens of OUDamong low-income, racial/ethnic minority individuals. In Phase 1, we propose to refine and finalize the PRC-delivered Peer Activate model and address barriers to implementation for Phase 2 using pre-intervention focusgroups with PRCs, staff, clients, and other key stakeholders (n=24). We will establish the preliminary feasibility,acceptability and fidelity of Peer Activate in an open-label trial (n=30) and pilot Phase 2 study procedures,including collecting preliminary MOUD outcomes (MOUD retention and opioid abstinence at 3 months). Basedupon adaptations in Phase 1, we will then conduct a randomized, Type 1 hybrid effectiveness-implementationtrial to evaluate the effectiveness and implementation of Peer Activate vs. treatment as usual (TAU; n=200) onMOUD retention at six months (primary), MOUD adherence and opioid abstinence (urine toxicology), anddepressive symptoms (secondary). Implementation outcomes will be assessed at multiple levels (patient,provider, organization), including assessments of feasibility, acceptability, fidelity, and adoption guided byProctor's conceptual model of implementation outcomes. Our multidisciplinary team aims to develop anevidence-based PRC-delivered treatment model that can be sustainably delivered to improve MOUD retentionfor low-income, minority individuals with OUD.",2020,2021,"Univ Of Maryland, College Park",129436,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C06922,3R01AA027782-02S1,A National Longitudinal Study of the Impact of COVID-19 on Recovery Residences,"PROJECT SUMMARY/ABSTRACTSafe and stable housing is critical to recovery from alcohol and other drug disorders. Among individuals inrecovery from these disorders, those living in recovery housing are among the most vulnerable. Recoveryhousing is rooted in the social model of recovery, which emphasizes peer support in helping residents maintaintheir recovery. CDC guidance for the general public for managing COVID-19 as well as its guidance for sharedor congregate housing providers may present significant challenges for residential recovery residence operators.Because the majority of recovery residences operate with almost no formal third-party payers to reimburse oroffset costs of this service, furloughs and work stoppages for residents who are responsible for paying for thisservice may contribute financial hardship and closure of recovery residences. To better understand how recoveryresidence are responding to the COVID-19 pandemic and its impact on recovery housing, this applications aimsto: (1) Examine the extent to which CDC guidance and other best practice guidelines are being implemented inrecovery residences, identify residence and other contextual characteristics related to differentialimplementation, and describe changes in implementation over time; and (2) Examine how the pandemic hasaffected the availability and financial viability of recovery housing, identify whether this impact differs byresidence and other contextual factors, and describe changes in availability and financial viability over time. Toaddress these aims, the proposed study will add questions to the survey administered to residences (N=800)participating in the National Study of Treatment and Addiction Recovery Residence (NSTARR) project(R01AA027782). These questions will query the extent to which the COVID-19 pandemic has affected sourcesof revenue for the residence, policies and practices, and programming for residents. An additional 200 randomlysampled residences (stratified by US Census Division) will be asked to complete a COVID-19-specific surveythat also collects information on implementation of COVID-19 guidance to ensure resident and staff safety. Theseresidences will be geocoded and linked with US Census data, COVID-19 case rates, and geo-located data forfederally qualified health centers (FQHCs) and publicly-funded hospitals. They will also be resurveyed 6 and 12months later to track changes over time. Finally, operators of residences that are no longer open will be askedto participate in a semi-structured interview about the role that COVID-19 may have played in residence closure.",2020,2023,Public Health Institute,144053,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2019 +C06923,3R01AG058679-02S1,Preserving Cognitive Resilience: A Biracial Parent-Offspring Study (18-4674) - Feasibility Study,"The specific aims of the parent NIA grant (R01AG058679, MPIs: Rajan & Evans, 2019-2024) has threecomponents: (1) Investigate factors, including behavioral and social factors, associated with epidemiologically-derived cognitive resilience in a biracial population study, the Chicago Health and Aging Project (CHAP: Age65+ years, 60% African Americans [AAs]); (2) Recruit a biracial offspring cohort, Parent Offspring Resilienceand Cognitive Health (PORCH: Age: 40-64, 50% AAs) study; (3) Examine whether cognitive resilience inparents are associated with global cognition and risk of MCI and dementia in offspring. Coronavirus disease2019 (COVID-19) has devastated global populations and has had a large impact in the United States. Thetransmission of COVID-19 is strongly influenced by population demographics, behavioral, and socialcharacteristics, factors which might also have a substantial impact on cognitive function by increasing the riskof MCI and dementia in older parents and midlife offspring, and by reducing cognitive resilience in olderparents, the primary outcomes of the parent grant. The one-year Administrative Supplement will test the feasibility of community-level COVID-19 testingthrough self-administered SARS-CoV-2 RNA nasal swab and fingerstick antibodies testing. Crucially, it canprovide preliminary data on the impact of COVID-19 infections, and behavioral and social factors, such as,household environment, pandemic stress, and social distancing on cognitive health in 100 older CHAP parentsand 100 midlife PORCH offspring with 50% AAs. This administrative supplement will conduct a feasibility studyto test SARS-CoV-2 antigens and antibodies in a well characterized, ethnically diverse, community-basedparent-offspring study with a large number of AAs. Additionally, provide feasibility to enhance the researchvalue of the parent PORCH study by expanding parent grant Aims 1 and 3 through adding COVID-19 to theexposures leading to decreased parental cognitive resilience and expanding parent grant Aim 3 by addingbehavioral and social characteristics and COVID-19 to the exposures leading to impaired offspring MRIIndices, cognitive performance and BP, and feasibility to examine possible racial/ethnic differences in theseeffects.",2020,2023,University Of California-Davis,401861,Human Populations,Black,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2019 +C06925,3U19MH121738-02S1,Mental Health Research Network III,"Summary:The Mental Health Research Network conducts practice-based mental health research in large healthcaresystems serving over 25 million patients in 16 states. The network has the potential to dramatically improve thespeed, efficiency, relevance and impact of mental health clinical and services research. A primary aim of thisnetwork is to have large-scale data infrastructure available for rapid analysis.With the onset of the COVID-19 pandemic, healthcare systems quickly changed from using mostly in-personclinic visits to telehealth visits that use phone or video to care for patients. However, we do not know how thechange to telehealth affects people with mental health conditions. This supplemental application uses theinfrastructure of the Mental Health Research Network to examine how changing from office visits to telehealthvisits disrupts care of people with mental health conditions in three healthcare systems. We want tounderstand how this change to telehealth may affect people differently, including people of racial or ethnicminority groups, patients who speak a language other than English at home, children or teenagers, olderadults, people with schizophrenia or bipolar disorder, people living in rural areas, or people living in areas withlow income or education. We also want to understand how these changes affect the severity of someone'sanxiety or depression, whether they keep taking their mental health medications or continue going to therapy,whether they visit the emergency department or need to be hospitalized in the mental health unit, or whetherthey have increased risk to attempt suicide.Understanding the effects of transitioning to telehealth visits will help us understand who is, and is not, as ableto access and engage in healthcare in future times of crisis - when going to the doctor's office in person maynot be safe - so that we can offer those patients more help and support. In addition, this research has broaderimplications regarding who benefits and who needs more support as the field of behavioral health carecontinues to rapidly transition to more regular use of telehealth services moving forward.",2020,2024,Kaiser Foundation Research Institute,344930,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2019 +C06926,3R21CA236652-02S1,METAL-ORGANIC FRAMEWORK AS PROTECTIVE COATING FOR CANCER BIOSPECIMEN PRESERVATION,"Through this Administrative Supplement to R21CA236652, we propose to explore the applicability of a novel biospecimen preservation technology (developed as a part of the parent grant) in preserving the structure and functionality of COVID-19 patient biospecimens. COVID-19 research and clinical diagnostics rely on the availability of high-quality biofluids. Within these biofluids, the integrity of molecular biomarkers and the quality of information obtained from their analysis is highly dependent on the storage conditions during pre-analytical phase. Unfortunately, due to the poor stability of biomolecules (especially proteins) at ambient temperatures, they are prone to lose their structure and biofunctionality before analysis. Hence, an extensive distribution network of refrigeration, the ""cold chain"", is necessary to maintain an optimal temperature during transport, storage, and handling of these biospecimens. Apart from causing a huge financial and environmental burden, the cold chain system is simply not feasible in pre-hospital and resource-limited settings such as urban and rural clinics, as well as developing countries with low and moderate incomes, where refrigeration and electricity are not guaranteed. Moreover, when the biofluids are frozen, decrease in thermodynamic free energy and unfavorable ice crystal-protein interactions can occur during subsequent thawing, which can further compromise analyte integrity. The above considerations clearly suggest the need for an alternate approach for preserving molecular biomarkers in biofluids during the pre-analytical stage, preferably, without the need for refrigeration. In this exploratory project, we propose a novel approach that involves the use of metal-organic frameworks (MOFs) as encapsulants for preserving the integrity of biomarkers in biofluids under normal (nonrefrigerated) storage conditions. The approach suggested here is transformative in that it completely eliminates the need for refrigeration and avoids unwanted freeze-thaw cycles and overcomes a huge economic and environmental burden. This energy-efficient and environmentally-friendly approach not only represents a novel technique to eliminate the cold chain and temperature-controlled handling of COVID-19-related biospecimens, but also allows interruptible, storable, and restorable on-demand detection at a later time in a centralized manner/location to improve the reliability of clinical diagnostics. Towards this ultimate goal, we will develop and assess the MOF-based preservation of SARS-CoV-2 antibodies (IgG and IgM) in patient serum/plasma under temperature and humidity fluctuations.",2020,2021,Washington University,157500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,"Medicines, vaccines & other technologies",2019 +C06927,3R01AI145988-02S1,Pre-clinical assessment of JAK inhibitors to ameliorate cytokine storms in Down syndrome,"ABSTRACT.This application is being submitted to PA-18-591 in accordance with NOT-AI-20-031.The recent emergence of SARS-CoV-2 and COVID-19 has created an urgent need for rapid deployment oftherapeutic strategies to combat the current pandemic, and major efforts are underway to develop new vaccinesand antiviral medications, however, results from these efforts are not expected in the near term. A moreimmediate approach is to repurpose existing therapeutics approved by the FDA for other conditions to remediatesymptoms associated with the most severe COVID-19 outcomes, potentially saving lives and reducing theburden on the healthcare system. Within this framework, cytokine release syndrome (CRS) also known ascytokine storm or hypercytokinemia, has been implicated in acute respiratory distress syndrome, heart failure,and death in patients with COVID-19 (1-5). However, although diverse immune-suppressive strategies toattenuate the cytokine storm are being tested in clinical trials for COVID-19, there is a dearth of pre-clinical datasupporting their use to attenuate cytokine-driven pathology. Therefore, we propose here to test the ability ofFDA-approved inhibitors of Janus Kinases (JAKs) to mitigate rampant cytokine production and multi-organinflammation in a mouse model of non-infectious lethal immune hypersensitivity.This mouse model has arisen directly from our work over the past five years that revealed a major role for immunedysregulation in Down syndrome (DS). We demonstrated that individuals with Trisomy 21 (T21), the molecularcause of DS, exhibit constitutively active interferon (IFN) signaling driven by presence of four of the six IFNreceptors (IFNRs), located in a single locus on chromosome 21 (chr21) (6). Follow-up studies have revealed 1)signs of IFN activation and chronic inflammation, including numerous cytokines related to CRS, in the plasmaproteome of people with T21 (7, 8) and 2) widespread immune dysregulation and IFN hypersensitivity in theblood of people with DS (9, 10). As part of our ongoing work to understand the role of interferon dysregulation inDown syndrome (DS), we recently discovered that the Dp16 mouse model of DS is lethally hypersensitive tochronic innate immune stimulation with the TLR3 agonist polyinosinic: polycytidylic acid [P(I:C)]. Unpublishedpreliminary data in this proposal include: · P(I:C) treatment of Dp16 mice triggers release of cytokines, including several recently linked to poor prognosis in COVID-19, such as MCP-1, MIP-1α, and IP-10. · The lethal immune hypersensitivity in this model is associated with multi-organ inflammation and liver damage in particular. · The lethality, cytokine release, and inflammation induced by P(I:C) can all be blocked with the JAK1- specific inhibitor INCB054707.We hypothesize that JAK inhibitors are a therapeutically viable strategy to ameliorate COVID-19associated cytokine release syndrome and associated morbidities. As such, our proposal is responsive toNOT-AI-20-031, particularly as a project ""developing medical countermeasures and suitable animal models forpre-clinical testing of vaccines and therapeutics against SARS-CoV-2/COVID-19"". Furthermore, and in keepingwith the spirit of the parent award, our data indicate that individuals with DS are likely to be a high-risk group thatmay experience more severe COVID-19 symptoms and associated cytokine storms in response to SARS-CoV-2 infection. For this administrative supplement, our specific aim is:1. To define the ability of all four FDA-approved JAK inhibitors to block lethality and associated cytokinestorms in a mouse model of immune hypersensitivity.Encouraged by our preliminary results with the JAK1-specific inhibitor INCB054707, we propose here to test theability of additional JAK inhibitors to rescue the hyperinflammatory phenotype in the Dp16 mouse model of Downsyndrome. We will compare the four FDA-approved JAK inhibitors: baricitinib, ruxolitinib, tofacitinib, andupadacitinib, which have differing specificities for JAK1, JAK2, JAK3, and the related kinase TYK2, as well asvarying pharmacodynamic and biodistribution properties. We will define the efficacy of each inhibitor and thetherapeutic window in which inhibition of immune stimulation can be achieved. In addition, we will characterizehyperinflammation in key organs and tissues (e.g. lung, heart, liver) at the histological and molecular level todefine how these organs respond to JAK inhibition.Importantly, our model system and study design allow for the assessment of inflammation in various tissues,many of which are linked to poor prognosis in individuals with COVID-19 (11-16). Completion of this aim willprovide a considerable amount of pre-clinical data in support of ongoing clinical trials aimed at treatingdeleterious immune responses and serve to bolster the selection of agents available as COVID-19 therapeuticsin the near term.",2020,2021,University Of Colorado Denver,257044,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Prophylactic use of treatments",2020 +C06928,3R01AG057389-04S1,Resident-to-Resident Elder Mistreatment Intervention for Dementia Care in Assisted Living,"7. Summary/ Abstract: Proposed is an administrative supplement to the grant, Resident-to-Resident Elder Mistreatment (R-REM)Intervention for Dementia Care in Assisted Living. The proposed supplement address Covid-related behavioraland social outcomes both cross-sectionally (n=400) and longitudinally (n=200) by adding a Covid experiencesmodule to an ongoing assessment. The parent study is a cluster randomized trial to evaluate an innovativestaff intervention in assisted living residences (ALRs), and addresses the goal of comparing the effectivenessof treatments in managing behavioral disorders in people with Alzheimer's disease and related disorders(ADRD). The proposed supplement addresses the goal of evaluating how social distancing requirementsaffect the care and well-being of vulnerable older adults in ALRs, including individuals with mild cognitiveimpairment and ADRD. Front line staff is ideally suited to inform intervention research and to serve asmeaningful collaborators in promoting best practices, including those aimed at keeping residents engaged,such as technological interventions to enhance connections with music, art and social engagement withfamilies. The proposed study addresses the following specific aims:Aim 1 (A1). Describe Covid-related experiences of fear, loneliness, engagement in isolation-mitigatingtechnologies, care satisfaction, and environmental quality.Primary Aim (A2). Examine cross-sectionally and longitudinally the multivariate effects of Covid-relatedexperiences (social isolation, loneliness, fear, stress) of residents on the outcomes of anxiety, depression andbehavior, controlling for personal characteristics such as cognition, co-morbidity and physical function. Hypothesis: Covid-related experiences will contribute uniquely to negative outcomes; these effects will be mitigated (mediated) by technological and other interventions to reduce isolation and loneliness.Aim 3 (A3). Evaluate the impact on staff of Covid-related experiences in terms of heightened resident behavioral aggression, staff stress, burden, burnout as well as positive caregiver experiences. Social isolation due to COVID-19 social distancing restrictions in assisted living and other such settingsmay increase the risk of poor behavioral, cognitive, psychological and health outcomes. Identifying isolation-reducing interventions and examining their potential mediating role in ameliorating adverse outcomes isimportant, and has implications for future such catastrophic events. The results are likely applicable to the over1.2 million residents of ALRs, many of whom have significant care needs and dementia-related behaviors. Theproposed project is an important step in developing approaches and interventions for ameliorating andpreventing social isolation in ALRs. Such interventions have the potential to improve quality of care, enhanceresident safety and quality-of-life and reduce behavioral disorder associated with social isolation in general, infuture crises, as well as during the current pandemic.",2020,2022,Hebrew Home For The Aged At Riverdale,154867,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2017 +C06929,3R01AG057525-04S1,Neurovascular dysfunction in delirium superimposed on dementia,"Abstract: As many as 20-30% of all COVID-19 patients develop delirium during hospitalization, an estimate that increasesto 60-70% in those that develop severe illness. Delirium is a well-established risk factor for dementia, thus theimpact of the ongoing pandemic on neurodegeneration will be long-lasting. In particular, we hypothesize thatCOVID-19 infection will accelerate the progression and emergence of Alzheimer's Disease Related Dementias(ADRD) in the elderly by increasing both peripheral and central inflammation as well as decreasing the ability ofthe lungs to supply the brain with sufficient oxygen to maintain normal cognitive function. This supplement toRO1AG057525 ""Neurovascular dysfunction in delirium superimposed on dementia"" seeks to model the systemicimpact of inflammation, akin to the pathology reported in patients with COVID-19 infection, on the central nervoussystem (CNS) by focusing on the neurovascular unit (NVU) and delirium-like behavior as key endpoints from ourparent grant. Furthermore, we have recently reported on the protective effects of our drug in development,URMC-099 on the NVU after orthopedic surgery in mice with ongoing neurodegeneration. We are well-positionedto rapidly evaluate the effects of this therapy after lung injury using methodological approaches established forour parent grant. Our overall objective for this supplement is to determine the impact of the inflammatory milieuon the NVU and cognitive function after lipopolysaccharide (LPS) inhalation as a simplified model of COVID-19-related delirium. The central hypothesis is that inhaled LPS induces platelet aggregation, neutrophil adhesion,and neurovascular hypoxia - key pathologic hallmarks found in patients with COVID-19. We contend that thesesequelae are preventable by treatment with the brain penetrant mixed-lineage kinase (MLK) inhibitor URMC-099. Our hypothesis is based on preliminary data acquired in the applicants' laboratories and will be tested bypursuing 2 specific aims: 1) To implement an inhaled LPS-based lung injury model to translate the clinicalfeatures of systemic COVID-19 infection by quantifying indices of neutrophils, neutrophil extracellular traps(NETs), platelets and cytokine release syndrome as the basis for CNS dysfunction; 2) To define inflammatoryevents at the NVU and related cognitive impairment in mice treated with inhaled LPS and reposition URMC-099to prevent these sequelae. Feasibility for these models and techniques has been established in the applicants'hands. In this innovative approach, real-time in-vivo brain imaging and postmortem analyses will be combinedwith novel behavioral assays to define delirium-like changes in mice. The rationale for the proposed research isthat successful completion will advance our understanding of how COVID-19 affects CNS function and providenew molecular mechanisms of relevance to aging, delirium, neurodegeneration, and the Alzheimer's Diseaseand Related Dementias at-large. Such knowledge is highly significant because COVID-19 infection during thispandemic will impact millions of older adults and at-risk patients in the United States with ongoingneurodegeneration and dementia.",2020,2022,Duke University,322620,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Disease models | Disease pathogenesis | Pre-clinical studies,2017 +C06930,3R01AG030611-13S1,COVID-19 Supplement to LitCog IV: Health Literacy and Cognitive Function Among Older Adults,"We are seeking a supplement to our ongoing study ('LitCog'; R01AG030611) in order to conduct two parallel,complementary investigations of the longer-term impact of COVID-19 on older adults' lifestyle behaviors,psychological & physical function, socioeconomic circumstances, healthcare use, access & adherence totreatment, and health outcomes. First, we will extend our current inquiries to now determine whether LitCogparticipants with cognitive impairment are experiencing greater challenges in accessing care and managingpersonal health due to COVID-19 compared to cognitively 'normal' adults. Such a natural experiment is possiblewith LitCog; since 2007 we have tracked declines in cognition, as well as onset of cognitive impairment, and theresulting impact on self-management of chronic conditions among diverse, community dwelling, older adults. Wewill leverage our recent renewal award, with data capture from active patients (N=776), involved caregivers(N=100), electronic health (EHR) and pharmacy records, and add 5 telephone interviews conducted every 4months to address the following primary aim:Aim 1 Investigate whether poorer cognitive function or MCI prior to the COVID-19 outbreak is associated with inadequate use of healthcare services and/or poorer health status.Second, we will also extend our LitCog-linked, Chicago COVID-19 Comorbidities (C3) cohort study. In March2020, as cases of COVID-19 were emerging in Chicago, our team rapidly responded by launching a survey tounderstand how older adults with chronic conditions, at greater risk for COVID-19 complications, wereresponding and taking action (or not) to prevent infection and disease spread. LitCog participants (n=153), aswell as patients enrolled in four other active studies (N=673) with uniform data collection for a large set of patientfactors and similar access to EHR and pharmacy records were recruited. Interviews were conducted duringChicago's COVID-19 outbreak phase (March 13-20), rapid acceleration phase (March 27-April 3), and apexphase (May 1-19). Our findings revealed many high risk adults lacked critical knowledge of COVID-19 symptomsand ways to prevent harm, did not feel susceptible to the virus, felt unprepared for the outbreak, were not socialdistancing or ensuring they had adequate supplies of prescribed medications. Disparities were revealed; blackadults, those living below poverty level, with low health literacy and poorer cognition were less prepared. Movingforward, the C3 cohort will also be followed as the LitCog cohort in Aim 1, allowing us to combine both cohortsand more directly investigate the longer-term impact of stress due to COVID-19 on the health and behaviors ofadults with chronic conditions. Our secondary aim is to:Aim 2 Examine adults' perceived stress from COVID-19 and its associations with lifestyle & self-management behaviors, healthcare use, patient-reported and clinical outcomes over time.",2020,2025,Northwestern University At Chicago,391278,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Approaches to public health interventions | Indirect health impacts | Social impacts,2007 +C06931,3DP5OD028162-02S1,Robotic Lung Ultrasound for Triage of COVID-19 Patients in a Resource-Limited Environment,"PROJECT SUMMARYNovel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on a pandemic of epicproportions, affecting over 8 million humans in an estimated 100 countries. A global response to prepare healthsystems worldwide is of utmost importance. Respiratory symptoms are the primary manifestation of COVID-19,and the disease caused by SARS-CoV-2 can range from mild illness to severe, acute and fulminant respiratorydistress. This varying severity in the face of a worldwide pandemic necessitates rapid diagnosis to provide theproper triage and disposition of patients. Diagnostic testing such as plain-film radiography (x-ray) and chestcomputed tomography (CT) are considered the mainstay of diagnostic imaging in the detection of lung-relateddisease. Lung ultrasound (LUS) has emerged as an alternative to x-ray and chest CT for rapid diagnosis ofCOVID-19 affected patients with major advantages include safety, absence of radiation, low cost, and itsportability for ease of bedside diagnosis. Guidelines for LUS imaging in COVID-19 patients have been proposed.However, LUS imaging is highly operator dependent. In resource-limited areas, the accessibility is limited by thesmall number of physicians and sonographers who are properly trained in providing accurate diagnosis.Additionally, LUS imaging requires close physical proximity between the operator and patient, which could leadto an increased risk of COVID-19 transmission. Therefore, there is a unmet need to develop a more accessibleLUS system for COVID-19 patients, whereby reducing physical contact between the operator and patient. In this proposal, we aim to develop a safe, low-cost, and easy-to-use robotic LUS platform to 1) maximize theaccessibility in a resource-limited environment and 2) minimize the risk of COVID-19 transmission betweenpatients and healthcare workers. This robotic platform will be designed to conduct LUS procedures followingestablished diagnostic workflows, while ensuring adequate safety. The proposed gantry-based robot platformallows the operator to tele-operatively manipulate the ultrasound probe based on visual information fromcameras. Thus, the operator is not required to be present with the patient, improving accessibility. An optimaltissue-probe contact pressure will be maintained by an electronics-free passive mechanical configuration toavoid excessive contact forces and ensure patient safety. The gantry system is structurally simple, low-cost, andeasy to implement in a research-limited environment. Specifically, we propose to evaluate the robotic LUSplatform with the active-passive hybrid control (Aim 1), demonstrate the safety and cross-validation in healthyvolunteers (Aim 2), and demonstrate the system reliability and performance in COVID19 patients (Aim 3). Thisproposed robotic LUS platform (1) makes the LUS procedure more accessible in a resource-limited environment,(2) minimizes the risk of contagion between patients and healthcare workers and, (3) establishes standardizeddata collection of LUS to improve the efficacy. The proposed system has the potential to play a critical role inmaximizing healthcare function via triaging of patients suspected to or have been diagnosed with COVID-19.",2020,2021,Worcester Polytechnic Institute,386461,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,,2020 +C06932,3U01AG066529-02S1,T Cell and Monocyte Telomere Length Dynamics in Patients with COVID-19,"Summary: Severe lymphopenia, expressed in decreased numbers of CD4 and CD8 T cells, increases the risk of dying fromCOVID-19. Regardless of the underlying causes of the decline in T cells, replenishing their numbers throughmassive replication is likely vital for convalescence. Such a process depends on telomere length (TL), which canimpose a limit on T cell replication. The recovery from lymphopenia associated with COVID-19 might, therefore,stall in individuals with comparatively short telomeres, including older individuals, men, and those with cardio-metabolic disease. These individuals are more likely to have severe COVID-19 and die from the infection. Inaddition, short telomeres might contribute to a macrophage-mediated 'cytokine storm' in these patients. Thesubstantial inter-individual variation in TL from birth onwards means, however, that telomeres of some youngadults are as short as those of older adults. Despite their young age, such younger persons are also at increasedrisk for severe COVID-19-associated decreased number of T cells and increased number of dysfunctionalmacrophages. The aims of the project are to measure TL parameters in CD4/CD8 T cells and monocytes frompatients with mild and severe COVID-19, monitor their TL dynamics during the course of the disease, andexamine their relations with the levels of selected cytokines, previously shown to be elevated in patients withsevere COVID-19. Findings have the potential to identify adults of any age who are at increased risk of dyingfrom COVID-19, and guide therapeutic modalities to reverse COVID-19- associated decline in CD4/CD8 T cells,including agents that stimulate telomerase, the reverse transcriptase that lengthens telomeres.",2020,2022,Rutgers The State University of New Jersey,286285,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2019 +C06933,3U01AA021696-09S1,Impact of the Coronavirus Pandemic on Alcohol Consumption and Mental Health in Young People,"PROJECT SUMMARY / Abstract: The COVID-19 pandemic, best characterized as a disaster, is unprecedented in its impact on individuals,societies, and the economy. Of special consideration is the effect of the pandemic on the psychological wellbeingand behavior of young people. Here, we propose leveraging the longitudinal, multi-site National Consortium onAlcohol and Neurodevelopment in Adolescence (NCANDA) study (2012-2022) to investigate changes inwellbeing and behaviors, with a focus on alcohol use in response to the pandemic, in an established sample ofyoung people including moderate-heavy users and those at risk for alcohol use, and to identify risk and protectivefactors for distress in response to the pandemic. Using NCANDA, we are able to directly address researchobjectives of NOSI NOT-OD-20-097 to understand social, behavioral and economic impacts from containmentand mitigation efforts implemented to reduce spread of the COVID-19 disease, as well as downstream healthimpacts including substance use/abuse, and to determine risk and resiliency factors and outcomes.Unlike most research in this area, NCANDA includes neurobiological data critical to complement clinical andself-report data in understanding the complex and dynamic interactions leading up to and following a disaster.Also, with its accelerated longitudinal design and current age of participants spanning 17-28 years old, NCANDAis uniquely powered to disentangle age and pandemic related effects, unlike traditional same-age cohort designs.We propose supplementing the NCANDA project with a brief COVID-19 survey about alcohol use, mood, andother behaviors during the pandemic as well as COVID-19 exposure and pandemic-related distress,administered to participants in June 2020. To track long-term effects of the COVID-19 pandemic, the survey willbe re-administered in Winter 2020 and Summer 2021.By embedding this survey, time-linked to the pandemic, within the existing NCANDA dataset, we proposecharacterizing the impact of the COVID-19 pandemic on alcohol use, mental health, and brain in young people(Aim 1) and to evaluate risk and resilience factors for COVID-19 pandemic-related distress (Aim 2). We proposeusing advanced analytics, including machine learning approaches, to identify a `signature' from the richinformation captured by neuroimaging, clinical and self-report data prior to the COVID-19 pandemic, that predictsdistress versus resilience in the face of the COVID-19 pandemic. A machine-learning approach embraces thecomplexity of the COVID-19 pandemic-related influence and takes advantage of the multi-domains within theNCANDA dataset.The analysis proposed in this supplement will offer valuable longitudinal data in a well-characterized sample ofyoung people who are bridging developmental years into adulthood and that includes those at high risk for, orcurrent heavy users of, alcohol. Such information can be used to guide public health and intervention strategiesto benefit vulnerable young populations in the event of future disasters.",2020,2022,Sri International,198581,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2012 +C06934,3UH3AG057039-04S1,An Integrative Science Approach to Resilience: The Notre Dame Study of Health & Well-being,"Project Summary The purpose of the supplement is to collect data during this pandemic (a shared stressor) to:1) understand how vulnerable populations (such as older adults) interpret and deal with thestresses associated with Covid-19; 2) how this differs from aspects of their previous lives; and3) how the pandemic influences the data collection for the parent project. In addition, it is anopportunity to assess data on individuals in the Notre Dame Study of Health & Well-being(NDHWB) for whom we have up to 10 years of questionnaire data and 5 daily diary bursts) toassess the effects of this stressor on individuals in the study and how this may differ by age andcontext. In order to accomplish these goals we will augment the study with four 28-day dailydiary bursts and four global questionnaires on 450 individuals (including the 221 currentlyenrolled in the parent project). We collected daily diary data on 359 individuals (during the socialisolation phase (April) and plan to continue this as we transition back to ""normal"" to assess thepotential influences that range from a second outbreak to a full recovery (July, October,January, and April).",2020,2022,University Of Notre Dame,388906,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C06935,3P30AG031679-10S2,Feasibility of Remote Home Support Coaches to Decrease the Physical and Psychological Impact of Social Distancing on Older Adults,"Background: Millions of older Americans have to practice social distancing due to the COVID-19pandemic. It is anticipated that this will need to continue for many older people until an effectivevaccine is available. Due to these restrictions, most older people cannot take part in their regularphysical and social activities. Physical deconditioning occurs rapidly when older people reduce theiractivity level. This increases the risk of people becoming so weak that it limits their ability to do basicmobility activities like climbing stairs and walking outdoors. Muscle weakness and balance impairmentsare also major risk factors for falls and fall-related injuries, including fractures. Because people have losttheir usual sources of social connection, there is likely to be an increased incidence of loneliness (i.e. thefeeling of being isolated), social isolation (i.e. the lack of social connection and support) and depressionamong older people. Loneliness and social isolation were already serious problems for older peoplebefore this pandemic. Many organizations have put in place telephone calls by volunteers or paidemployees to reduce loneliness and social isolation by engaging in friendly companionshipconversations. However, there is evidence that tele-interventions by lay people that use brief behavioralactivation coaching are significantly more effective in changing important health outcomes thanconversational calls. Methods: This study will explore the feasibility, acceptability and preliminaryevidence of efficacy of telephone-based Behavioral Activation Coaching telephone calls to reduceloneliness and prevent deconditioning in n=50 older people recruited from primary care practices inBoston or senior living/assistive living centers near Baltimore. The intervention will be delivered entirelyremotely in 10 sessions over 4 months. Outcomes include measures of feasibility, safety andacceptability. Efficacy will be explored by measuring changes in daily steps walked using a wearablesensor, loneliness, function, disability, social isolation, depression, anxiety, and health care utilization.Patient reported outcomes will be measured by trained telephone assessors at baseline - and 4-monthspost enrollment. Implications: If the Behavioral Activation Coaching telephone calls are found to beeffective this model could be quickly disseminated to volunteer organizations, health systems orbusinesses that wish to support people who are social isolating due to COVID-19. The materials andresources to implement the Behavioral Activation Coaching will be made freely available online.",2020,2021,Brigham And Women'S Hospital,325895,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2008 +C06936,3R44GM121130-03S1,SampleStream: A Radically Simplified Platform for Protein Sample Preparation,"Abstract: The rise of the global SARS-CoV-2 pandemic has exposed serious weaknesses in our ability to respond to novelpathogens. Three major areas of improvement include the rapid development of vaccines, therapeutics, andserosurveillence. All three of these areas require tools that accurately assess the immune response across individuals.Vaccine development requires lot-to-lot quality control and requires an antibody test that establishes whether or not aparticular formulation has elicited antibody creation in the patient. Likewise, intimate knowledge of the antibodiescreated in populations with mild disease can provide valuable potential candidates for biologics that can be rapidlyproduced. Finally, the identity and amount of antibodies specific to a pathogen within an individual can indicatewhether or not an individual has been infected, and, importantly, whether or not they have lasting immunity.Integrated Protein Technologies has developed a technology called SampleStream that enables rapid purification andconcentration of large proteins, such as antibodies, prior to delivery to mass spectrometry. Herein, we propose usingthis technology to couple immunoprecipitation to mass spectrometry. Using the KingFisher flex platform from ThermoFisher, 96 serum samples can be processed simultaneously with magnetic beads coated with recombinant spike proteinfrom SARS-CoV-2. The resultant samples will contain the antibodies specific to the virus on a per-individual basis. Massspectral analysis of these antibodies will provide sequence and abundance information. When combined with patientoutcome data, this will enable IPT to identify the set of antibodies that are truly neutralizing in the broader population.Ultimately, these antibodies can serve as drug leads, can aid in vaccine development by ensuring a potent immuneresponse is generated, and enable surveillance and assessment of infection/immunity across the globe.IPT's technology and our ""plugin"" system enable us to rapidly integrate these platforms and SampleStream uniquelyprovides the high throughput interface with mass spectrometry. We have an opportunity to have a significant impact onthis crisis and template a new technology that will enable more rapid responses to future pathogens.",2020,2021,Integrated Protein Technologies Inc,318151,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C06937,3R44MD009454-04S1,Mobile Health App to Reduce Diabetes in Latina Women with Prior Gestational Diabetes,"Abstract Latino communities have been disproportionately impacted by the COVID-19 pandemic, being both atincreased risk and experiencing more severe illness when infected. Latinos living in Puerto Rico have alsobeen affected via access to healthy food. Even before the pandemic, access to healthy food had beenthreatened due to the unprecedented series of natural disasters, including Hurricane Maria in 2017. The onsetof COVID-19 has further threatened access to healthy food. Relatedly, social distancing rules, which limitaccess to beaches, parks and public recreation areas to prevent unhealthy crowding in these spaces, mayhave a greater negative impact on low-income Puerto Ricans who rely on these spaces for physical activity.While public health recommendations for healthy shopping, healthy eating, and physical exercise duringCOVID-19 have emerged, these recommendations have not targeted to Latinos nor are they available inSpanish. Puerto Ricans would benefit from targeted healthy shopping and eating guidance due to thewidespread food insecurity and poverty that already existed prior to COVID-19, and physical activity guidancedue to the COVID-19 related constraints to outdoor physical activity. Digital technology, which is widely used by Puerto Rico residents, is a way to help families engage inhealthy behaviors in the face of COVID-19, as it overcomes barriers by providing behavioral tools on healthyfood shopping and food preparation, and providing ways to increase physical activity. Tailoring thisinformation to Latinas, who typically manage shopping and food preparation in Latino families, wouldincrease its impact. To our knowledge, no digital health intervention has been specifically targeted to, andco-designed with Latinas to promote healthy food shopping, healthy eating, and physical activity duringCOVID-19. While such an intervention has potential value for many Latino subgroups, Puerto Ricansrepresent a high-priority target because of pre-existing vulnerabilities brought about by several naturaldisasters that preceded COVID-19. The overall goal of this competitive supplement is to develop a culturally- and individually-tailored Spanish/English digital health intervention to promote healthy food shopping and healthy eating, as well as physicalactivity, among Puerto Rican Latinas during the COVID-19 pandemic and its aftermath. This competitiverevision expands the scope of our current SBIR Phase II parent grant (Hola Bebé), which is building andtesting a digital health intervention with tools for healthy eating and physical activity for Latinas with a priorhistory of Gestational Diabetes Mellitus (GDM), as well as builds on our SBIR Phase I project (LISTA), whichdeveloped tools for healthy shopping and eating for Latinas. We are committed to the rapid dissemination ofthe mobile app during the pandemic and its aftermath, to Latina users of community health centers throughoutPuerto Rico, as well as other sites where Latinas access food.",2020,2021,Environment And Health Group Inc,184794,Human Populations | Other,Other,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2014 +C06938,3U01AA026976-03S1,ALCOHOLIC HEPATITIS CLINICAL AND TRANSLATIONAL NETWORK: LATE PHASE CLINICAL TRIALS AND OBSERVATIONAL STUDIES 6/9,"ABSTRACTDespite the high clinical significance, there is limited knowledge of the management and treatment of COVID-19. Patients with alcohol associated liver disease (ALD) and COVID-19 are at increased risk for severe disease,morbidity and mortality. There are also data that alcohol consumption increases during isolation, like that causedby social distancing measures enacted during the COVID-19 pandemic, therefore the incidence and severity ofALD is likely to increase. Current treatment approaches for patients with severe COVID-19 include antiviralagents and supportive care. In our preliminary and pilot studies we have observed sarcopenia or loss of skeletalmuscle mass and impaired muscle strength in patients with ALD. Sarcopenia and accompanying contractiledysfunction contribute to longer hospital and intensive care stay, greater need for ventilatory support and pooroutcomes in acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19. The ""cytokine storm""that occurs in patients with COVID-19 is accompanied by elevated circulating IL-6, and emerging data suggeststhat IL-6 inhibitors improve survival in patients with severe COVID-19. Despite the significant interest in IL-6inhibitors with multiple ongoing clinical trials underway, these agents increase the risk for secondary infections(a common occurrence in COVID-19) and are contraindicated in those with significant elevated plasmatransaminases. β-hydroxy β-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolicproperties, also inhibits plasma IL-6 while improving muscle mass and contractile function. We thereforehypothesize that COVID-19 worsens clinical outcomes and muscle loss in ALD patients, and that reversal ofmuscle loss by HMB through an IL-6 dependent manner will improve clinical outcomes in ALD patients. Thishypothesis will be tested through two interrelated, but independent specific aims: (1) establish the naturalcourse of COVID-19 infection in patients with ALD by determining whether COVID-19 is more severe inALD and whether COVID-19 worsens liver injury in ALD; (2) determine whether treatment with HMBimproves the acute and long-term consequences of COVID-19 in terms of skeletal muscle mass, skeletalmuscle function, and clinical outcomes in ALD patients. We will use clinical and biosamples to determineoutcomes and responses to intervention targeting the skeletal muscle in these patients. We anticipate HMB willreduce inflammatory markers including circulating IL-6, improve clinical outcomes in-hospital, reversesarcopenia, and improve long-term clinical outcomes. These human studies have the potential for immediatetranslation into clinical practice to rapidly improve immediate and long-term outcomes in ALD patients withCOVID-19. These studies will supplement the applicant's ongoing alcoholic hepatitis network grant supportedby the NIAAA.",2020,2023,Cleveland Clinic Lerner Com-Cwru,153563,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2018 +C06939,3U01HL152405-02S1,Colorado REACH Hub,"Project Summary: This application is being submitted by the Colorado AMC Research Evaluation and Commercialization Hub(REACH) in response to NOT-EB-20-008, Availability of Administrative Supplements on BiomedicalTechnologies for Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has had unprecedentedglobal impact. There is an urgent need to for accelerating the development, translation, and commercializationof technologies to address COVID-19. The National Institute of Biomedical Imaging and Bioengineering (NIBIB)is seeking applications from current grantees to develop life-saving technologies that can be ready forcommercialization within one to two years. The Colorado AMC REACH Hub is addressing one of the areasidentified in NOT-EB-20-008, specifically, the need for rapid point-of-care and home-based testing/diagnostics.The Colorado AMC REACH Hub has received three applications from the NIH that were initially submitted to theRapid Acceleration of Diagnostic Technologies (RADx-Tech) program, a $500 million effort to significantlyincrease testing capacity and accessibility for SARS-CoV-2, the virus that causes COVID-19. Many of theprojects that have been submitted to RADx-Tech have been deemed too early in development or have otherdevelopment challenges that have prevented them from meeting the selection criteria of increasing testingcapacity by the end of 2020. The three applications that were received from the NIH were selected by the RADx-Tech program for potential supplemental funding due to their promise and their suitability for commercializationassistance to be provided by the REACH program. REACH Hubs are designed to increase the speed andsuccess rate of translating biomedical academic discoveries into products to improve human health. Membersof an external review board with extensive experience in medical diagnostic technology development reviewedthe three RADx-Tech applications and approved them for acceptance into the Colorado AMC REACH Hubprogram. The three selected applications are: (1) Development of a point of care SARS-CoV-2 ELASA; (2)COVID-19 POC rapid antigen detection CLIA waived device; and (3) Rapid Synthetic Biology-Based Point ofCare Assay for SARS-CoV-2 Virus. The requested supplemental funding will be used to fund research toadvance these important projects through defined milestones and deliverables. The funding will include hiring aproject management team with extensive experience in commercializing diagnostic products to work with theexisting Colorado AMC REACH Hub project managers, the investigator's research team, and an NIHEntrepreneur in Residence to establish a product development plan that includes significant proof-of-conceptand/or validation milestones that can be met in less than 12 months. The project management team will closelymonitor progress on a regular basis with project support contingent upon satisfactory progress toward the agreedupon milestones/deliverables. The overall goal is to advance the projects to an inflexion point wherein thetechnology can be licensed to an existing or new company to further develop the commercial applications.",2020,2021,University Of Colorado Denver,1166125,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06940,3RF1AG057705-01S1,Nitric oxide-mediated changes in glymphatic and CSF systems in aging and Alzheimer's disease,"ABSTRACTSARS-CoV-2 contact with the organism starts with binding to its key receptor ACE2 which is highlyexpressed in the ciliated cells of the tracheal, bronchial, and nasal mucociliary epithelium. After binding,the virus inhibits the cilia beating in the airways and suppresses mucociliary transport, the first line ofdefense against invading microorganisms. Thus, augmenting the ciliary function may prevent the viralinfection at the very first steps or help fight the further propagation of the virus. ACE2 is also expressedin selected brain cells, underlying the neurological effects of SARS-CoV-2.The main objective of this supplement is to rapidly build a screening system, to identify drugs that canbe immediately applied for COVID-19 therapy, and to use the gained knowledge for expanding thescreen to a broader range of candidate compounds.In our NIA supported grant we discovered the critical role of the nNOS-NO-cGC-cGMP signalingpathway for ciliary activity in the brain and the airways. Here we describe our plans of targeting thispathway with clinically-approved drugs in order to augment cilia activity and airways clearance. Thisproject can be later extended to build a sensitive and powerful drug screen for anti-COVID-19 therapy.In our first Specific Aim we will develop a comprehensive computational toolbox and use it todetermine the key parameters (a signature) of the cilia activity in the airways' and brain ciliated cellsfrom humans and humanized mouse model. In the second Specific Aim, we will apply our setup todetermine the signature of the cilia response to S1, the main cell binding ligand of SARS-CoV-2, and toS1-expressing pseudotyped VSV-S1 virus. Finally, in our third Specific Aim we will examine anti-SARS-CoV-2 drugs currently used in clinic and clinically-approved compounds that activate the NO-cGMP pathway, as well as their combination to determine if such treatments can rescue the S1-affectedcilia activity in the airways and brain preparations. In the same set of experiments we will examine theresponse of preparations from animals of different age, which may contribute to the profound old age-bias of COVID-19. We emphasize that our selection of drugs to be tested is limited to thetherapeutically-approved compounds, thus enabling rapid translation of our findings into clinicalpractice.",2020,2022,Stony Brook University,463521,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2017 +C06941,3R01MD011575-05S1,Social stressors and inflammation: A mixed methods approach to preterm birth,"ABSTRACT Black women are more likely to become ill with COVID-19 than Whites, with disparities reported in manycities including Detroit, one of our sites. Black women are overrepresented in the low-wage essential workforceand more likely to live in disadvantaged neighborhoods (e.g., crowded housing) facing challenges in socialdistancing. Blacks have less in the way of savings and possibly less flexible employers than Whites, increasingrisks for economic hardship (e.g., loss of jobs). Black women may experience discrimination in obtainingtesting and medical care for COVID-19 symptoms for themselves and their families. Due to ""shelter in place""policy and job losses with the pandemic, Black women may also experience increased conflict with their partnerand higher rates of intimate partner violence (IPV) due to families spending nearly all waking and sleeping timetogether. Racial disparities -- in COVID-19 prevalence and death rates, employment, neighborhood conditions,economic hardship, IPV, and discrimination in testing and medical care -- may all increase psychologicaldistress (e.g., depressive symptoms) for Black women. However, no published research has examined Blackwomen's experiences during a viral pandemic such as we are now experiencing. We hypothesize that Blackwomen will experience more discrimination, economic hardship, conflict with partner, IPV and psychologicaldistress as well as lower levels of support during the pandemic than pre-pandemic. Our cohort is comprised of 658 Black women from the Detroit, MI and Columbus, OH metropolitan areas.As part of the R01 study, women completed questionnaires during their pregnancies (T1=pre-pandemic). Forthis supplemental study, women will complete an online survey (T2= during the pandemic) on a smart phone oranother device. The T2 survey will include key domains from the T1 survey (e.g., depressive symptoms, socialsupport, IPV) and provide a second critical time point in the context of the pandemic. We expect some domainsto be especially impacted by the pandemic (e.g., discrimination, stress). We also added items to captureCOVID-19 specific issues, including experiences within their network (e.g. family members sickened), as wellas measures pertinent to the situation (e.g., social isolation). A subsample of women will participate inqualitative interviews for an in-depth understanding of their experiences. We aim to: (1) Examine associationsof disadvantaged neighborhoods, racial discrimination and economic hardship with psychological distress atboth time points (T1 and T2); (2) Examine whether relationship with the partner, IPV, and psychological distressare impacted by the pandemic by comparing the pre-pandemic and during pandemic time points; (3) Examinehow social isolation and social support relate to relationship with the partner, IPV, and psychological distressduring the pandemic; and (4) Explore pregnant women's experiences during the COVID-19 pandemic throughqualitative interviews. Black women are especially vulnerable during the pandemic. The time-sensitive natureof the COVID-19 pandemic demands the immediate exploration of women's experiences.",2020,2022,University Of Central Florida,197610,Human Populations,Black,Adults (18 and older),Urban Population/Setting,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Social impacts",2017 +C06942,3R01CA208303-05S1,Determining the role of SARS-CoV-2 in driving premalignancy of the airway,"Project Summary/AbstractLung cancer is thought to develop in a stepwise fashion giving us the opportunity to intervene before it becomesinvasive. A novel approach to cure patients of lung cancer is therefore to develop a targeted chemopreventionstrategy to prevent the formation of lung premalignant lesions in the first place. My lab studies airway epithelialstem cells (AESCs) and the signaling pathways involved in their repair and regeneration after injury. Our studiesled us to the conclusion that premalignancy represents a state of excessive self-renewal of AESCs with a blockin differentiation and we identified several mechanisms involved in stepwise progression to lung cancer. Onesuch mechanism involves proliferation of AESCs via the Wnt-β-catenin pathway and in particular we found thatonly one of the differential phosphorylation sites, the tyrosine Y489 residue of the β-catenin protein, allowednuclear localization of β-catenin with concomitant TCF/LEF activation for proliferation. This phosphorylation ofβ-catenin at Y489 is not present in normal airway AESCs but persists in premalignant lesions and lung cancer. We have developed human and mouse in vitro models of premalignancy in the proximal and distal airwayepithelium by driving Wnt/β-catenin signaling. These models include the air-liquid interface model of proximalairway stem cell proliferation and differentiation (Aros et al, 2020) and a 3D lung organoid co-culture model withtype I and type II alveolar epithelial cells. We are currently infecting our lung premalignancy models withSARS-CoV-2, in collaboration with Dr. Arumugaswami at UCLA to assess how viral infection alters this aberrantresponse to injury. Our hypothesis is that SARS-CoV-2 infection in the setting of premalignancy with excessive proliferationof AESCs will result in persistent Wnt/β-catenin signaling which will prevent the resolution of premalignant lesionsand allow additional mutations to develop to drive invasive carcinoma. Our goal is to understand the effects ofSARS-CoV-2 on Wnt/β-catenin signaling and especially p-β-cateninY489 in premalignant lesions using thefollowing approaches:Specific Aim: To understand the role of SARS-CoV-2 on p-β-cateninY489 in proliferation of AESCs inpremalignant lesions. We hypothesize that p-β-cateninY489 is induced by SARS-CoV-2 for repair after infectionand prevents resolution of existing premalignant lesions.Specific Aim 1a: We will identify how frequently SARS-CoV-2 infection drives Wnt/β-catenin signaling and leadsto the p-β-cateninY489 in AESCs in proximal and distal airway models.Specific Aim 1b: We have identified a compound that prevents p-β-cateninY489 in AESCs (Aros et al, 2020) andwill test the effects of this compound on SARS-CoV-2 infected proximal and distal airway premalignancy models.Specific Aim 1c: We will use transgenic mouse models with loss of β-catenin in the AESCs of the proximal airwayand examine the effects on repair of the airway after SARS-CoV-2 infection.",2020,2021,University of California-Los Angeles,156000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2016 +C06943,3R01AG052340-05S1,"Durability of immune responses to SARS-CoV-2 infection in the context of HIV-infection, aging and cross-reactive immune responses.","SUMMARY/Abstract: There is almost no information about the immune response to SARS-CoV-2, the causative agent of COVID 19.What little we know has either emerged in real time during the 2020 pandemic or has been gleaned from ahandful of studies on SARS-CoV-1. The pressing question at the moment is whether individuals who haverecovered from infection with SARS-CoV-2 will have durable immune responses that are protective againstreinfection and recurring illness. Current efforts to address this question are largely focused on antibodyresponses as they are not only easier to measure than T-cell responses, but antibodies provide the first line ofadaptive immune protection and can often neutralize a pathogen before widespread infection occurs.However, T-cells are also essential in providing protection against secondary infection and T-cell memory isideally elicited by vaccination. Understanding the T-cell response, both the quality and durability to naturalinfection with SARS-CoV-2, will not only provide insight into the pathogenesis of SARS-CoV-2, but will beimportant for vaccine development. However, HIV-infected individuals, with immune system deficits, representa highly at-risk population for morbidity and mortality from SARS-CoV-2. It is therefore critical to understandhow this population responds to this virus and to vaccination against SARS-CoV-2. To investigate this, we willcharacterize IgG as well as CD4+ and CD8+ T-cell subsets in the MWCCS participants who have hadconfirmed infection with SARS-CoV-2, either through a clinical test to detect virus, or by the presence of post-infection antibodies. Responses to vaccination, when the vaccine is available, will also be studied andcompared to the responses elicited by active infection. IgG and T-cell responses within the HIV-infectedpopulation in response to infection and vaccination will be compared to the responses observed in their HIV-seronegative peers within the MWCCS. The IgG titers and the frequency of SARS-CoV-2 responsive T-cells,their cytokine production, phenotype and durability will be analyzed in a longitudinal fashion until vaccinationoccurs or we have followed them for two years, whichever comes later. Numbers of senescent T-cells will bedetermined and associations investigated between the quantify of these cells and the post-infection immuneresponse and severity of disease reported. Pre-SARS-CoV-2 time points will both serve as case controls andallow us to investigate the potential presence of cross-reactive immune responses as two new studies suggestthat immune responses to other coronaviruses may be cross-reactive with SARS-CoV-2 which couldtheoretically impact immune responses to SARS-CoV-2 for better or worse. Our long-term goal is to informvaccine studies and public policies designed to protect older adults, particularly those aging with HIV.",2020,2021,University of California-Los Angeles,195000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2016 +C06944,3P50MD010428-05S1,Disparities in Exposure and Health Effects of Multiple Environmental Stressors Across the Life Course,"PROJECT SUMMARY The primary objective of our Center is to understand and reduce environmental healthdisparities (EHDs) by conducting three fully-integrated research projects applying novelmethods in epidemiology, exposure science, and cumulative risk assessment, with strongcommunity engagement across the Center. The Center emphasizes multiple health outcomesacross the life course with evidence for EHDs (birth outcomes, childhood growth rates, andcardiovascular mortality), in Massachusetts and within two low-income majority-minoritycommunities (Chelsea and Dorchester). The influence of housing and the neighborhoodenvironment on multiple exposures and health outcomes are emphasized throughout theCenter. Within Project 3, we use novel geospatial data and simulation techniques to provide anextensive and highly resolved set of chemical and non-chemical stressor exposures, includingspatially-resolved air pollution and temperature data generated in Project 1. In this supplement,we will leverage our Project 3 geospatial database of numerous social, housing, demographic,and environmental exposures across Massachusetts to evaluate racial/ethnic disparities inCOVID-19 cases, hospitalizations, and deaths. Our geospatial vulnerability data will be linkedwith individual-level COVID-19 data with address-level geocodes and daily temporal resolution,provided by the Massachusetts Department of Public Health. We will identify vulnerabilityfactors associated with disparities in incidence and severity of COVID-19 infection across citiesand towns in Massachusetts, modeling predictors of case incidence per 10,000 persons andhospitalizations per 10,000 persons by city/town over time. We will also apply novel methods tocharacterize spatiotemporal clustering, allowing us to determine differences in spatiotemporalpatterns of COVID-19 spread within and between cities/towns, including as a function ofindividual characteristics. Finally, we will examine differences in city/town-specific policies,implementation of state policy, and resident perception of public health recommendations, todetermine if observed patterns can be explained in part by between-city differences. With theseanalyses we will identify COVID-19 hot spots in Massachusetts and how cases spread withinand between communities, including the hardest-hit majority-minority communities, and we willdetermine the vulnerability factors that best explain these exposure and health outcomedisparities.",2020,2021,Harvard University,221125,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2015 +C06945,3U54HL119145-07S1,Boston Biomedical Innovation Center,"A well-recognized gap exists in the path from biomedical discovery in academia to clinicalapplication and commercialization of therapeutic, device, and diagnostic technologies incardiovascular, pulmonary, hematologic, and sleep disorders. This chasm is the result ofinadequate funding for support of proof-of concept or validation studies essential for early stagedevelopment; insufficient access to the resources and expertise needed to develop newtechnologies; and a lack of knowledge and experience among academic investigators in bringingnew ideas to commercial realization. Within the partnering institutions included in this application,the essential elements exist with which to build the infrastructure needed to support and sustainthe uninterrupted, durable flow of inventions from discovery through development andcommercialization. While these institutions have a clear track record of remarkably successfuldevelopment of many biomedical technologies, most of these commercial successes have beenachieved by the tenacity of individual inventors rather than with the help of committed institutionalmechanisms. We proposed to address these key shortcomings by establishing the regionalBoston Center for Accelerated Innovation in Therapeutics, Devices, and Diagnostics for Heart,Lung, Blood, and Sleep Disorders (B-BIC, or the Boston Biomedical Innovation Center). The keyobjectives of this Center. are to: 1) develop an integrated infrastructure that would expand theuniverse of commercializable technologies for heart, lung, blood, and sleep disorders; 2) placethese opportunities in the proper evaluative context through an engagement ('seed it'), solicitation('find it'), and selection ('pick it') strategy; 3) efficiently and effectively bring those selected to anappropriate exit point from the development process; and 4) provide the educational andmentoring infrastructure necessary for the development of the proper entrepreneurial skills amongacademic innovators. By achieving these goals, B-BlC would change the culture of our academicenvironment, as well as the relationship between the public and private sectors in facilitatingsuccessful development strategies for technologies in heart, lung, blood, and sleep disorders forthe ultimate benefit of patients and society.",2020,2021,Brigham And Women'S Hospital,1760250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2020 +C06946,3P30AG028747-15S2,University of Maryland Claude D. Pepper Older Americans Independence Center (UM-OAIC),"ABSTRACT :Identifying patients at risk for severe complications (i.e. respiratory failure, shock, or multiorgan dysfunction)following COVID-19 infection represents a critical challenge. The case fatality rate in COVID-19 indicates thatolder people are dying at a higher rate than other age groups, with 80 percent of deaths occurring in those olderthan 65 years. However, predicting disease severity in COVID-19 patients remains elusive.Humans co-exist with a vast and complex set of microbes (termed the microbiota) that extensively interact withthe immune system and have the ability to trigger pro- or anti-inflammatory responses. Recent studies suggestthat the host immune status is influenced by a fine balance of pro- and anti-inflammatory signals generated, inpart, by the microbiota. This balance is most likely disrupted in patients with severe acute respiratory syndromecoronavirus (SARS-CoV-2). Given that previous studies have shown an association between inflammatory statusof the patient and severity of the COVID-19 infection, characterizing the impact of the microbiota in SARS-CoV-2 infection might prove critical to predict disease severity. The objective of this study is to define the associationbetween the proinflammatory microbiome and the risk of developing ARDS in elderly patients with coronavirusinfection admitted at University of Maryland School of Medicine. Our hypothesis is that pro-inflammatorymicrobiota is associated with airway epithelial destruction leading to severe coronavirus infection. The proposedwork has the potential to identify pathway(s) involved in development of more severe complications of viralinfection which can guide new treatments.This supplemental grant expands the current scope of University of Maryland Claude D. Pepper Center (UM-OAIC) research to identify new and critical microbiota-based targets for diagnostic and therapeutic applications,in order to improve outcomes and decrease disabilities in elderly patients diagnosed with Coronavirus infection.Our long-term goal is to develop novel microbiota-based targets for diagnostic applications and new treatmentsto reduce time on the ventilator, ICU and hospital stay with additional goals of rapid discharge home and returnto a meaningful quality of life. We propose the following specific aims:SA1: Characterize the associations between human microbiota and ARDS in elderly patients infected withcoronavirus.SA2: : Evaluate the T-cell repertoires, cytokine profiles associated with proinflammatory microbiota and ARDSin patients older than 65 in comparison with patients younger than 65 years old.SA3 : Evaluate if a proinflammatory microbiome is associated with worse outcomes (longer hospital length ofstay and time on the ventilator) in comparison with anti-inflammatory microbiome.",2020,2021,University Of Maryland Baltimore,386092,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2006 +C06947,3R43MD014923-01S1,Fourth Trimester-A Web-based Tool For Postpartum Care To Address The needs Of Underserved Women,"PROJECT SUMMARY/Abstract: The postpartum period is a critical time, and more than half of all maternal deaths occur postpartum. Blackwomen are 3-4 times more likely than white women to experience maternal mortality. In the US, 1 in 4 womendo not have a timely postpartum visit, and adherence is even lower for women on Medicaid managed careplans. Our Parent Grant (R43MD014923) was funded to develop a program that educates and supportsmothers in the 'fourth trimester', to address the physical, cultural, and knowledge barriers to quality postpartumcare. The COVID-19 crisis presents novel health and economic challenges for this vulnerable population.Because of the myriad challenges COVID-19 presents, and the ways in which it will transform postpartum care,it is our responsibility to revise the scope of our project to address COVID-19 in our research and to addfeatures to the tool we are building to address immediate concerns and needs related to this crisis. Thechallenges of the current pandemic will have a lasting impact for minority and economically at-risk populationsbecause fundamental health disparities persist, further inhibiting already limited access to timely andappropriate care. Racial and ethnic minority women are more likely to have gaps in health insurance coverage,a situation further complicated by the higher proportion of unemployment during the pandemic and ensuingeconomic crisis. In addition, there are over 30 million small businesses in the US hard hit by this dual crisis -many of which are in the healthcare sector. They are critical for providing services to this vulnerable populationand are most at risk of losing their businesses during times of economic instability. Research focused on theconcerns, needs, and health of underserved women, and the development of digital tools to reduce gaps incare which specifically address barriers exacerbated by COVID-19, are essential to protect the health ofmothers and their babies. Our strong relationships with community groups and healthcare providers, andsupport of the RI Department of Health, Brown University, Goldman Sachs 10KSB, and Social EnterpriseGreenhouse, enable us to immediately begin to broaden our scope to learn more about the COVID-19 impacton underserved women and the provider community that supports them. We propose to expand our scope to: •conduct qualitative research activities to obtain specific input regarding the COVID-19 pandemic and economiccrisis from pregnant and recently postpartum women and conduct interviews with the healthcare supportnetwork during the COVID-19 crisis; • expand the scope of the prototype to include specific content respondingto feedback on needs related to COVID-19; and • systematically assess the impact of the prototype on keyhealth outcome measures through a modest pilot study. We will focus on resilience as a key outcome and willmeasure related factors such as depression, anxiety, healthcare utilization, and postpartum experiences.These activities will provide a baseline for longitudinal data collection in Phase II; result in an even strongerprogram for postpartum care; and provide valuable data for future interventions and policies for this population.",2020,2021,Orange Square Design Inc,168215,Human Populations,Black,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Health service delivery",2019 +C06948,3U54HL119893-07S1,UC BRAID Center for Accelerated Innovation COVID-19 diagnostic project development,"PROJECT SUMMARY/Abstract: The University of California Center for Accelerated Innovation created new mechanisms leveraging its diversestrengths in diagnostics, therapeutics, and devices to support translation of promising early-stage inventions forpatient benefit. The Center is a consortium of five UC medical campuses: UC Davis, UC Irvine, UC Los Angeles,UC San Diego, and UC San Francisco. Each campus has a thriving research enterprise, nationally rankedmedical school, and translational research institute funded by Clinical and Translational Science Awards (CTSA).The Center taps into the vigor and creativity of California's legendary biomedical and engineering ecosystemand integrates the many successful business, engineering and health sciences programs at our campuses. Ourprogram partners with well-established biomedical companies, venture capital firms, industry organizations andnonprofits focused on medical innovation. The Center is supported by UC Biomedical Research Acceleration,Integration, and Development (UC BRAID), a joint effort of the five UC biomedical campuses designed tocatalyze and accelerate biomedical, clinical, and translational research across the UC system. Together we: 1)Engage University of California heart, lung and blood disease innovators in entrepreneurism through acomprehensive education, training and mentorship program. 2) Solicit and select technologies with highcommercial potential that align with NHLBI's mission and addressed unmet medical needs or significant scientificopportunity. 3) Incubate our most promising technologies in accordance with industry requirements to facilitatetheir translation to commercial products that improve patient care and enhance health. We are now leveragingthis infrastructure and our network to support the development of COVID-19 diagnostic technologies of highpriority to the NIH.",2020,2021,University of California-Los Angeles,2760000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06949,3UH3DK114920-04S2,Nicotinamide Riboside for AKI in COVID-19 positive inpatients,"Project Summary / Abstract: Acute kidney injury (AKI) has been as high as 68% in COVID-19 patients admitted to intensive care unit (ICU)and 90% in patients on mechanical ventilation in New York City, NY. Moreover, up to 86% of deaths wereassociated with AKI using standard Kidney Disease: Improving Global Outcomes (KDIGO) definition. Kidneycontain abundance of mitochondria and impaired mitochondrial function is now well recognized as a majorsusceptibility feature for AKI. It is generally believed based on histopathological evidence that the underlyingorigin of AKI is inflammation or ""cytokine storm"" which suppresses PPAR-gamma-coactivator-1alpha (PGC1α)- the primary regulator of mitochondrial biogenesis and a regulator of nicotinamide adenine dinucleotide (NAD+).Lower availability of NAD+ limits existing mitochondrial function by reducing electron donors to the mitochondria.Stimulation of pathways that lead to enhancement of NAD+ appears to be beneficial in mitigating AKI occurrenceand severity in both animal models and humans. Recent studies using oral Nicotinamide (NAM) andNicotinamide Riboside (NR) as NAD+ donors have been found to be safe, well-tolerated, and upregulate NAD+pathways in a dose-dependent manner. In addition, NAM use during perioperative period in patients undergoingcardiothoracic surgery showed reduced incidence of AKI in a small number of patients without any adverseevents. It has been demonstrated that NR is more orally bioavailable than NAM and has no major adverse eventsin Phase I studies. At the present time no standard medical treatment for AKI is available and supportive careremains the mainstay of therapy. Therefore, the application of agents to safely restore mitochondrial functionmay provide a major benefit for reduced incidence and severity of AKI and potentially lower multi-organ failureand mortality. We specifically hypothesize that at admission supplementation with NR will improve markers ofAKI including indices of mitochondrial function in SARS-CoV-2 patients without significant adverse events. Wewill test this hypothesis in a pilot clinical study named: NIRVANA: NIcotinamide Riboside in SARS-CoV-2pAtients for reNAl protection. The primary aim of this pilot study is to determine the effects of NR to reduceseverity of AKI in newly admitted patients with SARS-CoV-2 using a randomized, double-blinded placebo-controlled clinical trial of 10-day consecutive treatment with oral nicotinamide riboside (NR) 500 mg twice daily(versus placebo). The primary outcome will be incidence of AKI defined by the KDIGO guidelines. A total of 100SARS-CoV-2 patients ≥18 years of age admitted to hospitals affiliated with 3 major medical academic institutions(University of Texas Health San Antonio (UTHSA), Icahn School of Medicine at Mount Sinai, New York, NY, andUniversity of Washington at Seattle (UW) will be enrolled into this pilot study. To evaluate secondary andexploratory outcomes, we will determine severity of AKI, the effects of NR on biomarkers of AKI andmitochondrial function by analyzing putative markers related to renal involvement, inflammation, andmetabolomics in timed biosamples collected from the study participants.",2020,2022,University Of Texas Hlth Science Center,502216,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 2 clinical trial,2017 +C06950,3P30AG066462-01S1,Alzheimer's Disease Research Center Determinants of health seeking behaviors during COVID-19 in persons with MCI/ADRD and their caregivers,"The recent pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or coronavirus disease(COVID-19), has disrupted much in the world. New York City and Columbia University Irving Medical Centerhave been the hospital at the COVID national and international epicenter. The psychosocial and functionalimplications of COVID-19 on our local population are myriad. The population affected by mild cognitiveimpairment and dementia (including Alzheimer's Disease (AD) and Alzheimer Disease-related dementias(ADRD)) faces high case fatality rates and major disruptions in care following necessary social distancing policesfor high risk persons. These changes have imposed new and unexpected personal and professional caregiverstrains. Specifically, the following have occurred in the population for whom our center provides care:a) the loss of potential direct contact with professional caregivers due to their own social distancingrequirements, new person caregiving responsibilities, personal illnessesb) limited excursions in the local environment out of concerns, for contracting COVID-19, andc) closure of myriad social day activities, both formal and informal.As a result, during periods of social isolation, persons with dementia are largely bound to their homes,confused by the chaos, and perceive and express the stress their family members experience. Moreover, manyof these same family caregivers must balance remote work responsibilities and family caregiving, often withinthe same home. Unfortunately, some of these circumstances are untenable and have led to illness,hospitalization, and death of some of our patients and research participants, as well as their family members.This proposal will explore the experiences, knowledge, attitudes, healthcare-seeking behaviors, andpsychosocial support related to the NYC COVID-19 epidemic, particularly among adults with normal cognitionbeing followed in the ADRC as well as care partners for those persons with pathological cognitive aging, as wellas socioeconomic determinants. It is hypothesized that many adults will have experienced adverse outcomes,been impacted in their personal and professional caregiver expectations, and variably demonstrate COVID-19specific health seeking behaviors, as well as had care impacted, particularly those of advancing age or caringfor others with advancing age, in ethnic minorities, and disadvantaged socioeconomic groups.Better understanding health-seeking behaviors and determinants during and after the local COVID-19epidemic has potential implications both locally and potentially globally wherever community spread is growing.An effective survey instrument, with modules purposefully designed to be capture multigenerational effects maybe relevant to some time to come, until the current pandemic has passed, as well as future pandemics or otheremergencies which restrict social engagement and population movement.",2020,2025,Columbia University Health Sciences,161548,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C06951,3U54MD007579-35S1,PHSU Specialized Center in Health Disparities - Impact of COVID-19 on Life Experiences of Vulnerable Children and Families,"PROJECT Summary: SARS CoV2 is the novel coronavirus that presented in Wuhan, China on December of 2019 as a serious disease(COVID-19) associated to a severe acute respiratory syndrome. COVID-19 has spread with unprecedentedfacility around the world as a pandemic with catastrophic morbidity and mortality rates and widespread social,psychologic, and economic distress. The most severe clinical outcomes of COVID-19, viral pneumonia, severeacute respiratory syndrome, multiorgan failure, and neurologic disease, primarily affect high risk groups, suchas the elderly and those with co-morbidities, but critical illness can present in younger persons, including children.Pediatric experts have also expressed concern that children are at higher risk for malnutrition, behavioral andmental problems, child abuse and vaccine preventable diseases during this pandemic. Measures taken toprevent transmission also cause significant distress and increase the risk for long term mental health problemsin children and adults. While all in the population are perceiving the biologic, psychological, and systemicstressors of COVID-19, disease outcomes of the most vulnerable in society and those with health disparities areparticularly concerning. The main goal of the proposed work is to gain knowledge from ""protective responses""and resilience that vulnerable children and families from the Pediatric Outcomes of Prenatal Zika Exposure(POPZE) study are displaying in response to the COVID-19 pandemic. The POPZE children have special needsfrom a previous biological insult (prenatal Zika) and their mothers and siblings are vulnerable from socio-economic disadvantages and psychological distress. The study will pursue lessons in health equity from the lifeexperiences of these vulnerable children and families through two study aims, Aim 1: To describe the multilevelstressors and needs associated to COVID-19 in a unique group of vulnerable children with prenatal Zika infectionconsequences and their families, and Aim 2: To determine how COVID-19 associated stressors affect the lifeexperiences of vulnerable children and families and impact their health, family interactions, and quality of life. Weexpect that the responses that promote resilience will constitute a repertoire of culturally competent solutionsthat clinical and public health providers can use to promote the health and wellbeing of families at risk for healthdisparities in the face of adversity.",2020,2024,Ponce Health Sciences University,188389,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Disease pathogenesis | Approaches to public health interventions | Indirect health impacts,1997 +C06952,3U54HL119810-07S1,Rapid Diagnostics of SARS-CoV-2/COVID-19 of People Wishing to Return to Work or School RADx Tech Project 5146,"Cleveland Clinic (CC) and its partners Case Western Reserve University, Cincinnati Children's Hospital Medical Center, The Ohio State University and University of Cincinnati have a longstanding commitment and documented success in transitioning laboratory and clinical innovations into dramatic improvements in patient care, CC alone, via its commercialization arm CC Innovations (CCI), has generated 53 spin-off companies and $644 million in equity financing in the past decade; however CCI has a focus on more mature programs and does not reach back into the research pipeline. Also, contributing to commercialization success of the applicant institutions has been the establishment of the state-funded Global Cardiovascular Innovation Center (GCIC) that has a mission of advancing late-stage cardiovascular innovations, i.e., 'shovel ready' opportunities with rapid job creation potential. The applicant consortium has now come together to address an unmet need by proposing a new Center (Cleveland Clinic Innovation Accelerator, CCIA) with an overall goal of propelling early-stage projects forward and educating researchers to be full partners in transforming their discoveries into high-impact advances in patient care. The proposed Center will enhance and coordinate the existing resources of the five partnering institutions to advance the very strong pipeline of laboratory discoveries and technical innovations generated every year in NHLBI mission areas (over 250 NHLBI-funded projects). This application has three specifics aims: (1) To create the CCIA - a self-sustainable, multi-institutional consortium focused on translating early innovations in NHLBI mission areas into advanced solutions for improving global patient care. CCIA will complement the mission of the GCIC by reaching earlier into the discovery and development pipeline in order to address the gap between discovery research and validation/pre-clinical development. (2) To select through rigorous peer-review commercially-promising NHLBI funded projects that will receive funds and expert project management. Projects shall span the technology range of diagnostics, devices, therapeutics and tools. (3) To create a nationally accessible institute for educating and mentoring researchers, clinicians and developers in biomedical innovation and entrepreneurism. The Center will provide experience-based training to cultivate a growing cadre of commercially successful innovators. Generation of the CCIA will thus create a self-sustainable engine for propelling a large pipeline of NHLBI-related research discoveries into advances in human health.",2020,2021,Cleveland Clinic Lerner Com-Cwru,406488,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +C06953,3R01CA237672-02S1,T Cell Immunity Of COVID19: Developing Biomarker And Therapeutic Strategies,"Abstract: Pancreatic ductal adenocarcinoma (PDAC) in its advanced stages, is refractory to conventional therapy, with amedian patient survival rate of 6-7 months and 1-year survival rate of 10-15%. Adoptively transfer of antigen-specific T cells represents a potentially effective strategy in combination with immune checkpoint blockade. Inthis proposal we address two major challenges to advancing the use of adoptive cellular therapy (ACT) forpancreatic cancers: 1. a paucity of proven immunogenic targets for pancreatic cancer and, 2. a means of rapidlydeploying antigen-specific cellular therapy targeting such antigens. Our scientific premise is that strategies thataddress the lack of tumor-reactive T cells in pancreatic cancer, where the mutational burden and immunogenicityis significantly lower, would be desirable and achievable by the adoptive transfer of tumor-reactive T cellsrecognizing pancreatic cancer-associated antigens.To address the challenge of identifying immunogenic targets for pancreatic cancer, we implemented an epitopediscovery workflow to analyze peptides eluted from tumor MHC by LC-tandem mass spectrometry. In thecourse of performing these studies, we cross-indexed predicted epitopes against the virus Uni-Prot database toidentify potential tumor-associated epitopes representing human endogenous viral sequences, and discoveredthat segments of the SARS-CoV2 viral genome are processed and presented by tumor MHC. Analysis of thegenomic sequences of K562 revealed that several regions of the of the SARS-CoV2 gene are present in intronsequences and we propose in this supplement to interrogate additional tumor genomic and RNA sequencingdatabases to identify additional epitopes associated with SARS-CoV2 and other viruses to determine 1) theirimmunogenicity (ability to elicit high affinity virus- and tumor-specific T cells) 2) prevalence among tumortypes. We believe this to be an unprecedented source of immunogenic epitopes that can be used to developpredictive/ prognostic algorithms (TCR clustering) and for therapeutic intervention (antigen-specific adoptive Tcell therapy and vaccination) for malignancies as well as for the treatment of SARS-CoV2 and other coronoviraldiseases. This supplement proposes to identify these novel epitopes in alignment with the objective proposed inAim 3 of the original R01 application.",2020,2024,The University of Texas MD Anderson Cancer Center,149511,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2019 +C06954,3U54MD013376-02S1,RCMI@Morgan: Center for Urban Health Disparities Research and Innovation (1),"PROJECT SUMMARYCOVID-19 infections are disproportionately higher among communities of color, nationwide(CDC, 2020). In Maryland, where 60% of the population is white and 30% is black, the rate ofcoronavirus infections is higher among African Americans (AA) at 49.4% compared to 36.9%among whites, and 13.7% among Asians and among other races (MD Department of Health,2020). Likewise, AAs account for 53% of COVID-19 deaths within Baltimore's Northeastcommunity (i.e. zip code 21215), and, in one of Baltimore's Health Enterprise Zones (HEZ) (i.e.,21216, 21217, 21223, and 21229) four of five infected residents are black (David, P., 2020). Low-income underinsured/uninsured AAs with COVID-19 symptoms often experience transportationbarriers. Even when they are able to arrive at an emergency room (ER) they often are turned away(Shamus, K., 2020). Other members of this population elect not to go to the ER and instead dealwith the painful COVID-19 symptoms at home. To make matters worse, the long history ofsegregation nationwide has forced many AAs into housing areas with limited access to local healthclinics, healthy food options, clean air, and green space, all of which contribute to higherincidences of pre-existing illnesses, which increases the risk of experiencing more severe COVID-19 symptoms.To address the aforementioned problems, the Morgan State University (MSU) School ofArchitecture and Planning (MSU-SAP), MSU Department of Psychology, MSU Department ofGeography, AA biomedical company Juxtopia, University of Maryland, and engineeringconsulting company Contronic LLC, will investigate an innovative concept of rapidly renovatingBaltimore's vacant/underused houses/buildings, located in lower-income Baltimore HEZcommunities and zip code 21215, into temporary clinics. The goal of the project is to provide targetresidents with easier accessibility to culturally aware and competent healthcare services (i.e.,local/community healthcare facilities and resources (i.e., healthcare providers)) to measurablydecrease the health disparity in COVID-19 related infections and mortality rates inBaltimore. The MSU-SAP team hypothesis is that IF some Baltimore City-ownedvacant/underused properties in HEZ and 21215 communities are renovated into hybrid clinics,THEN residents in those communities will have access to efficient and more culturallycompetent healthcare services compared to traditional healthcare facilities (e.g., ERs). Toaccomplish this research, the investigators will address the following specific aims:Aim 1: Assess the impact of the clinic-desert phenomenon on the COVID-19 outbreak inBaltimoreAim 2: Develop a methodology to identify optimal locations for potential temporary communityclinics for testing, vaccination and other related healthcare services during outbreaks andpandemics such as COVID-19Aim 3: Assess the feasibility of converting a vacant or underused building into a temporarycommunity health clinic during times of public health crisis, such as COVID-19",2020,2024,Morgan State University,188693,Human Populations | Other,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,Health service delivery,2019 +C06955,3R01AI072726-10S1,Biological role of SARS-CoV2 Superantigenic structure in hyperinflammatory syndromes,"PROJECT Abstract: The Coronavirus Disease 2019 (COVID-19) pandemic has been associated with the emergence of a new febrilepediatric entity called multisystem inflammatory syndrome in children (MIS-C), that involved systemichyperinflammation, multiorgan involvement and gastrointestinal symptoms. In some cases, this syndrome alsodemonstrated clinical attributes, such as persistent fever, rashes, conjunctivitis and generalized pain in theextremities, that mirror some features observed during Kawasaki Disease (KD). MIS-C patients are critically illand present with prominent cardiogenic shock and impressive myocardial dysfunction. While initially designatedas ""Kawasaki-like"" because of the few features that were reminiscent of KD, it has been suggested that thesevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger KD in children, however manyclinical laboratory as well as cardiac findings indicate that MIS-C and KD are different entities, and that MIS-Cpresents more similarities with toxic shock syndrome (TSS), which is triggered by bacterial or viral superantigens.In recognition of the NIH Strategic Plan and the urgent need for research on Coronavirus Disease 2019 (COVID-19) and its causative agent, SARS-CoV-2, here we propose to expand the planned studies of our R01 by addingexperiments examining the role of SARS-CoV-2 superantigenic activity and its connection to the emergence ofMIS-C. Our preliminary computational analysis of SARS-CoV-2 suggest that the virus has a superantigen (SAg)motif between the S1 and S2 spike proteins. However, this specific finding needs to be assessed biologically inMIS-C patients and by in vitro experiments using human PBMCs.Therefore, we hypothesize that KD and MIS-C are distinct entities triggered by different immune mechanisms,and that the aberrant immune response observed in MIS-C patients is the result of SARS-CoV-2 superantigenicstimulation. We propose to investigate the hypothesis that the SARS-CoV-2 SAg motif triggershyperinflammation in MIS-C patients and severe COVID-19 cases by performing the following supplementalspecific AIMS 1) Determine the involvement of a Superantigen (SAg) in the pathogenesis of MultisystemInflammatory Syndrome in Children (MIS-C) by characterization of the MIS-C patient T Cell Receptor(TCR) repertoire and 2) Determine if the Spike protein of SARS-CoV-2 possesses superantigen-likeactivity in vitro and in vivo. Successful completion of the aims of this administrative supplement could revealnew avenues to predict, prevent, and treat MIS-C and severe COVID-19 disease in adults.",2020,2021,Cedars-Sinai Medical Center,184894,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C06956,3P30AG031679-10S3,Assisted living communities- transforming predictive data into proactive care for COVID-19,"Abstract: Recent data suggests that that older Americans who contact COVID-19 are at greatest risk for hospitalization andpoor outcomes. Additionally, due to advanced age and their high likelihood of having multiple chronic conditions,adults in senior living facilities are at highest risk for developing COVID-19, its most serious complications, and dying. Since the identification of first US case of novel coronavirus 2019 disease (COVID-19) in the Seattle,Washington, several outbreaks have been identified in long-term care and assisted living facilities with evidence of rapid spread. Older residents and the staff of long-term care assisted living facilities as well as public health officials are facing a multitude of challenges which render early detection of COVID-19 infections difficult inthese facilities and which have posed a major barrier to the efforts to control the spread of infection. Adding tothese challenges, more than half of residents with positive COVID-19 test results are asymptomatic at the timeof testing, further contributing to transmission. There is an urgent unmet need for strategies for monitoringof residents in long-term care and assisted living facilities to facilitate early detection of the infectionusing means that require minimal person-to-person contact.While the dynamics of COVID-19 infection spread is being addressed by several contact tracing apps,assessing the risk for development of severe symptoms and hospitalization in these community residentsrequires active physiological monitoring and ecological momentary assessment in the context of preexistingclinical conditions and presents an immediate unmet need. With this project, we propose to deliver a user-friendly COVID-19 early detection alert platform (COVID-Alert) that integrates: 1) biosensor ensemble thatnoninvasively and continuously monitor and record critical vital signs (temperature, heart rate, respiratory rate,oxygen saturation, and activity level); 2) ecological momentary assessment (EMA) using the 5-question setreleased by CDC and adopted across US by healthcare providers and health insurance industry; 3) artificialintelligence framework that triggers an alert based on synthesis of real-time physiological biosensing data feed,EMA monitoring of symptoms, with personalized risk profiles of preexisting conditions derived from electronichealth record maintained by the facility.COVID-19 clinical decision support integrated into the workflow of long-term care facilities will ensure thatresidents receive appropriate and timely care (resident level) and ongoing surveillance to prevent an outbreak(facility level) while avoiding unnecessary staff exposure. This study brings together a strong interdisciplinaryteam of experts in engineering, informatics, data science, machine learning, and CDS. The advanced data-drivenpredictive model will be trained and validated using both high-dimensional EHR data and clinician feedback. Theprocess of the algorithm development and clinical implementation will be closely monitored and evaluatedthrough formative and summative evaluation.",2020,2021,Brigham And Women'S Hospital,371423,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management | Infection prevention and control,"Disease susceptibility | Supportive care, processes of care and management | Barriers, PPE, environmental, animal and vector control measures",2008 +C06957,3RF1AG063811-01S1,The impact of COVID-19 pandemic on community-dwelling older adults with ADRD,"Project Summary. Persons with ADRD face significant challenges under the pandemic of coronavirus disease2019 (COVID-19). First, persons with ADRD are at a high risk for COVID-19 because they are generally olderadults with comorbidities. In addition, persons with ADRD may have difficulty understanding the disease andfollowing the safety procedures, thus making them more susceptible to COVID-19. Furthermore, the generalramifications stemming from the pandemic may affect the usual medical care received by persons with ADRD.Persons with ADRD often have cognitive impairment and are likely to develop disruptive behaviors. Thus, theymay need routine medical and/or psychiatric services to manage their chronic conditions and to address theirmental health issues. They are more likely to benefit from in-person medical visits, which has been greatlyinterrupted during the pandemic. Although the CMS has expanded telemedicine benefits, persons with ADRDmay find telecommunication as the means of receiving healthcare, difficult. Lastly, the majority of persons withADRD live in community, and they may need in-person long-term services and supports (LTSS) to assist withtheir daily living and psychological or emotional care needs. The pandemic may have reduced the availabilityof these supports and services. In addition, caregivers (not residing in the same household) may have to wearpersonal protective equipment to deliver services, causing confusion and upset that trigger behavioral issuesamong patients. These changes in care may have made it more difficult for persons with ADRD to maintaincommunity living and may accelerate the likelihood of institutionalization. The impact of COVID pandemic onblacks with ADRD could be particularly significant. It has been shown that blacks with ADRD tend to havehigher levels of cognitive impairment than their white counterparts. At the same time, it has been revealed thatblacks are at disproportionally high risks for COVID-19 infection and death. These racial differences are likelytriggered by socioeconomic determinants. For example, blacks tend to aggregate in disadvantagedcommunities with fewer resources and supports and higher rates of COVID-19 infection. To date, it is unclearhow this pandemic affects persons with ADRD, both regarding the risk of and severity of COVID-19, aswell as their needs for usual medical care and LTSS (that are not directly related to COVID-19), andhow such impacts vary by individual's race. This proposed study has two Aims: 1) to examine the risk ofCOVID-19 and the severity of illness (hospitalization, ICU, death) among community dwelling older adults withADRD, and how that varies by individual's race; 2) to examine the impact of this pandemic on non-COVIDrelated health care utilization (e.g. hospitalization, ER visits, nursing home placement) among this population,and how that varies by race. The proposed research is significant as the findings will provide valuable andtimely information on how this public health crisis affects the vulnerable older population with ADRD, andinform future efforts aimed at reducing racial disparities in health among this already vulnerable population.",2020,2024,University Of Rochester,384975,Human Populations,Black | White | Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Indirect health impacts | Social impacts,2019 +C06958,3U01AA026108-04S2,Fetal Alcohol Spectrum Disorder in Adults: Health and Neurobehavior,"The 5-year award, for which this would be an administrative supplement in response to NOT-AA-20-011,focuses on the impact of prenatal alcohol exposure (PAE) on physical and mental health within the contextof social and environmental factors that may contribute to outcomes in adulthood. There are two important,and related, reasons to include attention to COVID-19 and the medical and social implications of thepandemic in this ongoing study of alcohol-affected adults. First, there is evidence that the adults in thelongitudinal cohorts being followed in Atlanta and Seattle are particularly vulnerable to the impact of thepandemic. Second, given this vulnerability, the pandemic represents a historic threat to the validity of studyoutcomes that must be addressed. In the parent study, 500 volunteers, half from each site will be seen forTier 1, that includes remote collection of self-reported health and demographic information. In Tier 2, 240individuals are being seen for more comprehensive assessment of health risk, immune status,neurocognition, and social functioning. To date, 226 individuals have completed Tier 1. Preliminary data,from Years 1-3, indicates that, in these samples, PAE is associated with higher risk for cardiovascularcompromise, intellectual and social dysfunction, and higher rates of substance use. The majority ofindividuals in these cohorts are from populations that have been identified nationally as more impacted byCOVID-19 infection and mortality (i.e., African-American; Native-American) and many in these groupsare highly anxious about the effects of the virus. Given these factors, we will collect information on theimpact of COVID-19 on health (e.g..,medical records), social outcomes (e.g., job loss, homelessness), andmental health status as well as substance use. COVID-relevant questionnaires will be administeredremotely to both those who have previously participated and to future participants allow measurement ofthe effects of the pandemic on these outcomes. In Atlanta only, an extra tube of blood will be obtainedduring existing blood draw for antibody testing. Finally, we will employ the National Death Index (NDI)to determine mortality rates over the past 10 years in the parent cohorts from which these samples are beingdrawn, allowing an estimate of mortality in these 902 individuals who have previously participated inresearch. We anticipate that individuals with PAE will show more impact on health during this emergencyand they may have a higher mortality rate than nonexposed individuals. Further, we anticipate that PAEwill be associated with greater anxiety related to COVID-Exposure and increased substance use. We alsohypothesize that social and environmental factors will contribute to the severity of effects.",2020,2022,Emory University,141308,Human Populations,Black | Other,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2017 +C06959,3UL1TR001414-06S1,"THE SEARCH FOR COVID-19 PREVENTION AND CURE: ADDRESSING THE CRITICAL ROLE OF INNATE/ADAPTIVE IMMUNITY BY INTEGRATING NOVEL INFORMATICS, TRANSLATIONAL TECHNOLOGIES, AND ONGOING CLINICAL TRIAL RESEARCH","Individual CTSA hubs are leading the national clinical and translational research efforts in developing newapproaches to address the COVID-19 pandemic. This crucial role was natural. Long before the current crisis,CTSA hubs were committed to translation, building multidisciplinary teams of investigators and communitypartners, overcoming regulatory burdens, ensuring quality in clinical and human research, developingtransformative informatics, and disruptive technologies for diagnostics and therapeutics. In this proposal, webuild on our center's active participation in meaningful clinical trials (e.g., the NIH Remdesivir RCT), the earlycreation of a biospecimen repository from COVID-19 patients, institutional commitment and fundraising that ledto a $3.5 million pilot fund distribution, a robust and accessible clinical database repository, and the ongoingwork of an NCATS-supported CTSA Collaboration Innovation Award (a coalition of the J. Craig Venter Institute,UCSD, UCI, and Stanford) focused on artificial intelligence approaches for the analysis of flow cytometrydata. Using the emerging informatics framework of supervised generalized canonical correlation forintegrative data analysis, we will link clinical data from COVID-19 patients enrolled in a variety of trials andat various stages of disease with innovative in vitro evaluation of innate and adaptive immunity, an areastill poorly understood in SARS-CoV-2 pathology, obtained from patient biospecimens to obtain mechanisticinsights of COVID-19 pathogenesis at a systems level. Innate and adaptive immunity are particularlyrelevant to COVID-19 disease pathogenesis because they play key, but distinct, roles at all phases of theillness (initial tissue-virus interaction; systemic responses; the cell-mediated cytokine storm leading to multi-organ failure and death, likely long after levels of viremia have fallen; and, ultimately, protective immunity). Thecurrent CCIA novel flow cytometry informatics research permits elucidation of dynamic cellular immuneresponses related to the COVID-19 pandemic that were heretofore unobservable. Using Hi-DAFi for masscytometry analysis, validated informatics pipelines for single cell transcriptomics analysis, and cutting-edgestatistical data integration and machine learning strategies tied back to the available clinical data we will beable to discover novel associations between cellular biomarkers and disease state, a particular therapy, anddisease mediating factors such as age, health disparities, and the presence of other diseases or conditions likeobesity. This information will aid in critical efforts to target new therapies and possibly identify idiosyncraticindividual physiologic variables that render certain patients who seem to have no known comorbidities morevulnerable to severe COVID-19 disease. Finally, the robust connection between the UCI hub and both regionaland national networks (e.g., BRAID, the coalition of the 5 UC CTSAs, and NCATS Trial Innovation Network)will provide an unprecedented opportunity to rapidly disseminate clinically relevant discoveries and engage thetalent and insight of the many clinicians and scientists working tirelessly to end this pandemic.",2020,2024,University Of California-Irvine,1088735,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C06960,3R01AI150305-01S1,"Interferon hyperactivity, COVID19, and Down syndrome","PROJECT SUMMARY.This is an application for an Urgent Competitive Revision to our Transformative R01 award funded by the NIHINCLUDE Project and NIAID titled 'Understanding Down Syndrome as an Interferonopathy'. The centralhypothesis of the parent award is that hyperactivation of interferon (IFN) signaling causes many of thedevelopmental and clinical hallmarks of DS. In this revision, we will investigate the interplay between IFNhyperactivity, immune dysregulation, COVID19 pathology, and immunity against SARS-CoV-2. We hypothesizethat IFN hyperactivity will modify the clinical course of COVID19 in DS, including long term immunologicalsequalae, while potentially impairing development of cellular and humoral immunity against SARS-CoV-2. OurSpecific Aims are:1. Determine the clinical and immunological characteristics of COVID19 in DS. It is increasingly evidentthat individuals with DS infected by SARS-CoV-2 are more likely to be hospitalized, develop secondary bacterialinfections, and die at younger ages. However, many questions remain unanswered about the clinical course ofCOVID19 in DS. What are the risk factors for severe COVID19 in DS? Are there treatment modalities that areless or more effective in DS? What are the sequalae of SARS-CoV-2 infection in survivors with DS? Here, wewill employ the National COVID Cohort Collaborative (N3C), the DS-Connect® registry, and the Human TrisomeProject (HTP) cohort study to generate a definitive assessment of the clinical and immunological characteristicsof COVID19 in DS. We will complete parallel analyses of the N3C database and data obtained by the HTP teamvia electronic health record Abstract: Ion and participant surveys to identify differences in early symptoms,immunological parameters, clinical course, risk factors, response to different treatment modalities, and long termsequalae, with emphasis on potential differences by age, sex, race/ethnicity, and geography.2. Investigate the immune phenotype of a cohort of COVID19 survivors with DS. Our extensive investigationof the immune phenotype of people with DS has revealed strong dysregulation of T and B cell lineages, includingchanges that could impair the development of cellular and humoral immunity against SARS-CoV-2 and theresponse to SARS-CoV-2 vaccines. Now, supported by the DS-Connect® registry and the HTP cohort study, wewill obtain biospecimens from individuals with DS that survived SARS-CoV-2 infection. We will include thesesamples in our ongoing pan-omics characterization of IFN hyperactivity and immune dysregulation in DS, whilealso investigating the development and duration of memory T and B cell responses and production of neutralizingantibodies specific for SARS-CoV-2.Altogether, these synergistic aims, which address multiple aspects of this NOSI, will advance our understandingof the impacts of trisomy 21 and IFN hyperactivity on COVID19 in DS, thus informing the rapid development ofcustomized preventive, diagnostics, and therapeutic strategies for this at-risk population.",2020,2024,University Of Colorado Denver,619607,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06961,3U01HL152410-02S1,Midwest Biomedical Accelerator Consortium: MBArC,"Summary: The NIH Rapid Acceleration of Diagnostics (RADx) initiative underpins the US national effort to developaccurate, rapid, user-friendly, and accessible testing for COVID-19 infection. The Midwest BiomedicalAccelerator Consortium (MBArC) is one of five national Research Evaluation And Commercialization Hub(REACH) centers funded by NIH to support the translation of novel scientific discoveries into business products that diagnose, prevent, and treat high-burden diseases affecting the US population. The purpose of thisadministrative supplement request is to leverage the highly aligned goals of the RADx and REACH programsby supporting three promising scientific teams that will develop novel and innovative technologies into point-of-care devices for diagnosing COVID-19 infection. Each scientific team will receive funding to perform proof-of-concept and product definition studies. The leadership of the MBArC hub will work closely with each team toassist them in achieving their milestones and de-risking their technologies. MBArC leadership will connectfunded teams to the academic and educational resources of the MBArC hub and REACH network. MBArCleadership will also work closely with NIH staff to promote the success of the funded teams and the RADxinitiative.",2020,2021,University Of Missouri-Columbia,1171566,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C06962,3R01CA201429-05S1,Helping the Poor Quit Smoking: Specialized Quitlines and Meeting Basic Needs,"Project Summary/Abstract: The impact of COVID-19 on low-income and minority populations has been profound, spanning health,employment, income, food, rent, transportation and daily needs like diapers and toilet paper. In Missouri,where the parent study and proposed supplement take place, disparities abound. African Americans make up<12% of the state population but over 40% of COVID-19 deaths - the second largest gap in the U.S. amongstates reporting race data. As of April 20, 2020, we have enrolled 1,743 low-income daily smokers in the parentstudy, a randomized trial testing two cessation interventions. Over half report annual household income<$10,000, most (59%) are African American, and many (30%) did not complete high school. They are alsosick: 50% report at least one chronic condition (28% asthma, 20% COPD, 15% Type II diabetes, 10% heartdisease), and 56% rate their health as ""fair"" (39%) or ""poor"" (17%). From March 9 to April 16, 2020, weadministered COVID-19 survey items to 88 participants. Awareness of COVID-19 was high, but protectivebehaviors were inconsistent, and occupational exposures were high: of those who worked - 74% AfricanAmericans - only 19% had been off work and 6% worked from home during COVID. In short, low-wageminority smokers, often in fair or poor health, were working outside the home, having more contact with others,but with little protective equipment. We propose a highly innovative study in this sub-group using intensivelongitudinal data collection and cutting-edge time series analyses to understand complex, dynamicrelationships among four factors identified as priorities in the RFA: (1) employment disruptions; (2) social andeconomic needs; (3) adherence to COVID-19 containment and mitigation recommendations; and (4) healthindicators and behaviors. The study will produce estimates that can be used to model adherence to protectivemeasures and disruption to daily needs, personal health, and health behaviors such as smoking in low-wageminority workers during pandemics.",2020,2021,Washington University,157486,Human Populations,Black | Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Indirect health impacts | Social impacts,2016 +C06963,3R01CA211044-04S1,Off-the-shelf engineered NK cells for the treatment of AML,"Abstract: The coronavirus (COVID-19) pandemic has spread rapidly and globally to infect over 3 million individuals, withno effective therapeutic options for patients with serious and life-threatening complications. The impact of thisinfection is likely to be especially serious in patients undergoing hematopoietic stem cell transplant (HSCT), inparticular umbilical cord blood transplant (CBT) recipients or those receiving chimeric antigen receptor (CAR)T or NK cell therapies, given their immunocompromised state, presence of medical comorbidities, and concernsfor higher infection-related severity and mortality. Our team has developed robust clinical banks of HLA-typedGMP-grade viral-specific T lymphocytes (VSTs) targeting cytomegalovirus (CMV), BK virus (BKV) andadenovirus. We have treated over 100 HSCT recipients, 49% of whom had received CB or haploidenticaltransplants, with these partially HLA-matched and off-the-shelf VSTs on FDA-approved clinical protocols with a>80% response rate and no toxicity. We have successfully applied this platform to establish the protocols for themanufacture of GMP-grade COVID-19 specific T cells. We propose to generate a biobank of COVID-19 specificT cells from donors who have recovered from COVID-19 infections using IRB-approved protocols (MDACCLab02-0630) in the MDACC GMP Facility. We will then conduct a phase I/II clinical trial to evaluate the safety,feasibility and antiviral activity of third-party, off-the-shelf, most closely HLA-matched COVID-19 specific T cellsin HSCT including CBT/haploidentical transplant or cell therapy recipients with severe COVID-19 infections (Aim1). To expedite the approval of this trial for our patients, we recently amended another VST protocol to includetreatment with COVID-19 specific T cells (MDACC #2017-0350, IND 17761).One of the most severe manifestations of the COVID-19 viral infection is acute respiratory distress syndrome(ARDS), often requiring mechanical ventilation and high dose corticosteroid therapy due to respiratory failure.Indeed, there is increasing evidence that the use of corticosteroids may reduce mortality in patients with COVID-19 related ARDS, especially if administered early in the treatment algorithm. However, COVID-19 specific T-celltherapy is not an option in such patients as corticosteroids induce apoptosis of adoptively transferred T cells,thus, significantly limiting the efficacy of this approach. To address this challenge, our group has developed anefficient and novel strategy to inactivate the glucocorticoid receptor (GR) in viral-specific T cells, using CRISPR-Cas9 gene editing of the Nuclear Receptor Subfamily 3 Group C Member1 gene (NR3C1- the gene encodingthe GR). In Aim 2 of this proposal, we will perform the IND-enabling studies for the production of GMP-gradeNR3C1 knockout COVID-19 specific T-cells in preparation for a subsequent phase 1 trial, to be funded throughalternative sources. Given our track-record of generating clinically effective viral-specific T-cells, we areoptimistic that our approach of adoptive immunotherapy with COVID-19 specific T cells will be successful inHSCT or cell therapy recipients with life-threating COVID-19 related infections.",2020,2021,The University of Texas MD Anderson Cancer Center,162000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Phase 1 clinical trial | Phase 2 clinical trial,2020 +C06964,3UG3NS105703-03S1,A Lung-chip microphysiological system to model SARS-CoV-2 infection and test novel therapeutics,"Project AbstractSARS-CoV-2 novel coronavirus has caused a pandemic, presenting us with an urgent need to develop newmodels to study the pathophysiology of infection and test innovative therapeutics to combat disease. Thisproposal aims to use chip-based microphysiological systems to establish a model of the human lung toinvestigate SARS-CoV-2 infection and test novel antisense oligonucleotide (ASO) therapies to reduce viralentry and replication. Using human primary and induced pluripotent stem cell (iPSC)-derived lung epithelium,we will generate both proximal and distal airway chip models, infect with live SARS-CoV-2, and test newlydesigned ASOs to target host cell components to prevent viral entry and conserved viral sequences to preventreplication. We have assembled an expert team of lung biologists, virologists, and pharmaceutical industrypartners to complement the iPSC and organ-chip technologies our lab has been developing over the past fiveyears. We feel that the approach presented in this proposal will yield rapid results by generating human-relevant models to better understand the pathological mechanisms of SARS-CoV-2 infection and test noveltherapeutic strategies currently in development by our pharmaceutical industry partner.",2020,2021,Cedars-Sinai Medical Center,1163750,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Disease models | Disease pathogenesis | Pre-clinical studies,2020 +C06965,3P30AG024824-16S1,"Coaching, Collaboration, Cleaning, & Communication: 4C Intervention to Reduce SARS-CoV-2 Transmission","Abstract: COVID-19 has spread rapidly across the globe in the six months since the novel coronavirus SARS-CoV-2 wasfirst detected in a cluster of patients with community-acquired pneumonia in Wuhan, China. As of June 10,2020, the Centers for Disease Control and Prevention (CDC) reports over 1.9 million COVID-19 cases and112,133 deaths in the US; the World Health Organization (WHO) reports over 7.1 million cases and 408,025deaths worldwide (in 216 countries). Advanced age and underlying conditions are risk factors for ICUadmission with COVID-19 infection, meaning nursing home (NH) residents are at greater risk for severe illness.At the same time, NHs have long faced special challenges in implementing effective infection preventionprograms, including limited resources and diagnostic challenges in a frail functionally disabled long-staypopulation. To date, approximately one in three deaths from the virus in the US have been linked to NHs orother long-term care facilities. Anticipating that the virus will return in the fall of 2020, advancing ourunderstanding of the transmission of SARS-CoV-2 within these facilities for vulnerable populations deservesurgent and further investigation. Environmental contamination with SARS-CoV-2 that is reported in limitedstudies highlights the potential importance of transmission between patients, their environment, and healthcareproviders via direct and indirect contact. With this proposal, we plan to characterize the epidemiology of SARS-CoV-2 in the NH patient room environment over time and the risk of transmission to near and far environments,with the explicit intent of developing integrated, simple COVID-19 infection prevention strategies. We willachieve these goals through the following aims. Specific Aim 1: Characterize transmission of the SARS-CoV-2 virus within post-acute care settings including patient rooms and common use areas such as nurses'stations, dining areas and recreation areas. We will conduct a prospective longitudinal study of older adultswith active COVID-19 infection at 4 NHs with designated COVID-19 units to describe risk factors for virustransmission. We hypothesize that risk factors including functional disability, comorbidities, and COVID-19symptom severity will be associated with increased odds of SARS-CoV-2 transmission to the environmentamong residents with active COVID-19 infections. Specific Aim 2: Using a cluster-randomized study design,we will test a multimodal aging-friendly intervention including four components (4Cs): 1) Coaching: infectionprevention coaching to observe, teach, and audit evidence-based infection prevention practices by all frontlineclinicians; 2) Cleaning: standardized recommended environmental cleaning protocols with feedback onenvironmental contamination; 3) Communication: patient and family communication strategy andimplementation of patient hand hygiene and recommended PPE use; and 4) Collaboration: rapid testing, re-testing and contact tracing, in collaboration with referral hospitals. We hypothesize that the implementation ofthis intervention will be associated with lower odds of SARS-CoV-2 transmission to the environment.",2020,2025,University Of Michigan At Ann Arbor,465657,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience","Disease transmission dynamics | Disease susceptibility | Barriers, PPE, environmental, animal and vector control measures | Communication",2004 +C06966,3R01HD094347-03S1,Molecular and Vascular MRI of Placenta Accreta,"An understanding of the transplacental transport of the SARS-CoV-2 virion is of enormous importance.Objective characterization of virion transport, even in animal models, is a hugely challenging task. Usingtransplacental transport as an example, we seek to address this problem: we will design and build a VirionSurrogate Particle (VSP). Binding of the VSP to target receptors (ACE2), and subsequent internalization willbe validated in cell culture, followed by in vivo testing of transplacental transport. The specific aims for thissupplement are thereore: 1. Prepare Virus Surrogate Particles (VSP), recapitulating the viral lipid envelope, bearing the Spike protein S on the surface and carrying proteolytic Furin in the lumen, and validate binding of VSP to the ACE2 receptor in cell culture studies. 2. Study trans-placental transport of VSP in the k18-hACE2 mouse model with the humanized ACE2 receptor throughout the course of pregnancy using MR, CT and fluorescence tracing of particles 3. Study the effect of known ACE2 receptor level effectors (low protein diet, hypertension, high fat diet) on transplacental transport of VSP",2020,2022,Baylor College Of Medicine,156621,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +C06967,3R01NS097719-04S1,A Nomogram to Predict Seizure Outcomes after Resective Epilepsy Surgery,"Project Summary: The full spectrum of neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been clarified. Previous studies have been limited to case series and have describedonly neurological complications observed in patients hospitalized with COVID-19 or admitted to intensive careunits. While these studies provide important information, they do not clarify the range of neurologicalmanifestations in individuals showing different severities of symptoms during infection, the long-term neurologicaleffects of the disease, and they do not provide any understanding of the pathophysiology of the disease.In our current project (1R01NS097719-04-A1), we have constructed a large data and biospecimen infrastructureto develop statistical models for individualized prediction of epileptic seizure-freedom and cognitive outcomesafter resective brain surgery for drug resistant seizures. In this competitive revision application, we propose topair our infrastructure (predictive modeling and genomic expertise) with institutional resources (Cleveland ClinicCOVID-19 Registry and Biobank) to advance the epidemiological and mechanistic understanding of neurologicalcomplications of COVID-19, particularly epilepsy, stroke, and delirium, and to generate nomograms and onlinerisk calculators for the relevant neurological COVID-19 complications.The objectives of this revised proposal are to characterize the incidence and manifestation phenotype of newonset seizures, stroke, and delirium in all patients diagnosed as COVID+ (3,177 as of May 7) in our healthcaresystem, to build and validate prediction models to identify individuals at risk of neurological complications, andto identify systematically disease modules (molecular determinants of disease pathobiology/physiology) forCOVID-19 that can reveal novel underlying mechanisms for SARS-CoV-2 associated neurologicalmanifestations.Older age, smoking, diabetes, hypertension, cardiovascular disease, kidney disease, chronic lung disease, andcancer correlate with progression to severe disease in patients hospitalized with COVID-19. We hypothesize thatthese factors are similarly associated with a higher risk of neurological complications. However, these ""riskfactors"" are not specific, occur in various combinations, and have limited value as isolated indicators of specificneurological complications. Our team's expertise will be used to generate nomograms and online risk calculatorsfor the relevant neurological complications observed in the CCHS COVID-19 registry cohort, to exploreunderlying mechanisms of these neurological complications using innovative human protein-protein analyses,and to generate tools that can guide decisions in clinical care.",2020,2022,Cleveland Clinic Lerner Com-Cwru,308248,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C06968,3K01AG056557-04S1,Style and Substance: Characterizing Dementia Caregiving Styles and Associated Biopsychosocial and Health Services Utilization Outcomes,"Abstract: The physical and emotional toll faced by the approximately 15 million Americans serving as family caregiversfor persons living with dementia (PWDs) is well-established, and the challenges posed by care provision duringCOVID-19 related distancing and shelter-in-place orders likely intensify experienced burdens. The NIA-fundedparent K01, ""Style and Substance: Characterizing Dementia Caregiving Styles and Associate Biopsychosocialand Health Services Utilization Outcomes"" (K01AG056557, PI: Amanda Leggett), characterizes distinctions inhow various caregiving styles react to internal care challenges (i.e. behavioral and psychological symptoms ofdementia, activities of daily living, etc.). This administrative supplement builds off that parent K01 by examininghow various defined caregiving styles cope and manage differently in the face of a global pandemic (COVID-19) and associated shelter-in-place orders. To better understand care styles at higher risk for negative careoutcomes and facets of care styles that may be targeted and modified in future caregiving interventions, thissupplement aims to 1) Identify the association between external COVID-19 care challenges (pandemic-relatedstress, social distancing, and shelter-in-place regulations) on caregiver distress and well-being; 2) Characterizehow identified cognitive-behavioral care styles uniquely perceive and behaviorally manage care in the face ofCOVID-19 care challenges; 2a) Explore caregiving styles as a moderator between COVID-19 related externalcare challenges and outcomes (care-related distress, well-being, informal and formal support seeking, andhealthcare utilization), and 3) Delineate caregiver's perceptions of barriers and facilitators to care duringCOVID-19 and what services and supports they would have found beneficial to pinpoint targets for socialdistancing relevant caregiving interventions. To accomplish these aims we will conduct in-depth mixed-methods interviews with 100 primary family caregivers for PWDs (as many as possible from our originalsample with refill recruitment to maintain a total sample of 100 participants). All participant contact will beconducted virtually by phone, web-based survey, and videoconferencing methods. This work extends thecareer development of the PI by expanding the caregiving styles model to incorporate cognitive-behavioralcare management across typical care and pandemic care contexts and offering additional training related to amajor public health concern which has critical implications for PWDs and their caregivers. Moving forward,insight from this research can inform us on how caregiving styles respond to internal and external stressorsallowing for the development of more efficient and effective caregiver-focused interventions tailored to theindividual's caregiving style.",2020,2022,University Of Michigan At Ann Arbor,21315,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Social impacts | Health service delivery | Individual level capacity strengthening,2017 +C06969,3UM1AI068618-14S2,"CoVPN 3002 A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222 for the Prevention of COVID-19 LAB","This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) VaccinesLeadership Operations Center (LOC) for implementation of the first COVID-19 vaccine efficacy trial ""A PhaseIII Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy,and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19.""With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 inSARS-CoV-2 infected individuals. Addressing this gap, the National Institute of Health (NIH) led rapidconstitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network ofphysician scientists at 64 United States (US) and 55 international clinical trial sites in 15 countries dedicated todeveloping globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing globalHIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as theLOC for CoVPN vaccine trials.This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of AZD1222, a recombinantreplication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein, tomodify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from up to 100clinical trial sites across the US, using data analytics to target high risk individuals with a diverse racial andethnic profile.Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will bemonitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals whoprogress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will bedone at CoVPN laboratories, using qualified and validated assays for diagnosis and immune monitoring.Specific aims of this study are to demonstrate efficacy of AZD1222 to prevent COVID-19, to evaluate thesafety, tolerability and reactogenicity of 2 injections given 4 weeks apart, to assess the ability to preventinfection with SARS-CoV-2, to assess the ability to modify COVID-19 disease, to assess the ability to preventemergency room visits, and to evaluate the binding and neutralizing antibody responses. This efficacy trial willtell us much about the adaptive immune response in persons who receive a SARS-CoV-2 S protein basedvaccine and about their ability to modify the disease course of COVID-19. In addition, it will improve ourunderstanding of the dynamics and duration of these responses and will inform rational design and testing ofpreventive and therapeutic monoclonal antibody interventions. Lastly, the results of this trial will be used toassess registration of this vaccine product as well as to modify future COVID-19 vaccine trials planned over thenext 12 months.",2020,2020,Fred Hutchinson Cancer Research Center,6554653,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C06970,3UH3TR002142-04S1,"Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS COV2 Drug Screening","Abstract: The appearance of SARS CVO2 in early 2020 has spurred efforts to limit the disease spread and developeffective treatments. The most promising long-term approach is a vaccine. While some vaccines are enteringaccelerated clinical trials, it may take 12 or more months before an effective vaccine is available. Even ifsuccessful, it may not be possible to treat everyone with a vaccine or the effectiveness of the vaccine may belimited. Given the severity of the disease among a number of those patients, alternative approaches to limitinfection should be developed. The goal of this proposal is to use human cardiac, vascular, and lung alveolarmicrophysiological systems (MPS) to identify possible compounds that block SARS COV2 entry into cells andtissues. While cell binding assays can be used to screen drug candidates, human MPS offer the advantage oftesting promising drug candidates under conditions encountered in the body. We propose a tiered approach inwhich primary cells and cells overexpressing angiotensin converting enzyme (ACE2) are used to identifypromising candidates that block SARS COV2 virus entry into cells, and vascular, cardiac, and lung alveolarMPS are used to provide a robust evaluation of drugs that block SARS COV2 binding. The first tier withindividual cell types enables a rapid screen and the screen with the microphysiological systems enables testingof the most promising candidates with the tissues most likely to be infected. We will develop the screeningassays using a pseudovirus with the SARS COV2 spike protein. In Aim 1, we will develop an assay forpseudovirus binding to ACE2 expressing cells by verifying binding and fusion to cells that express ACE2. Wewill whether the binding specifically involves the spike protein and determine the levels of binding sites on thecell types used in subsequent aims. In Aim 2, we will screen individual cells types for molecules that blockentry into the cell of pseudovirus expressing the spike proteins. Potential drug candidates include those thatpotentially block spike protein binding (e.g. spike proteins, Captopril, Lisinopril, human recombinant solubleACE2, and antibodies to the spike protein or ACE2) and those inhibiting Transmembrane Serine Protease 2(TMPRSS2), activity (e.g. camostat mesylate, nafamostat mesylate). In Aim 3, we will test most promisingcompounds in vascular, cardiac and lung microphysiological systems and compare against results from 2Dstudies. We will also examine the relationship between drug blocking and factors that affect ACE2 expression.",2020,2022,Duke University,280600,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis | Pre-clinical studies | Prophylactic use of treatments",2017 +C06971,3R33CA235319-02S1,Multi-color Mapping of Cancer Molecular Signatures and Tumor microenvironment,"AbstractSince the recent identification of a novel coronavirus from the pneumonia outbreak in Wuhan, China, now namedas SARS-CoV-2, the virus has spread globally very rapidly. SARS-CoV-2 is closely related to SARS-CoVemerged in 2003. While there are many factors associated the virus transmission, the pattern of SARS-CoV-2spread is distinctly different from that of SARS-CoV. Evidence shows that there is virus transmission beforeonset of symptoms in patients. Diagnosis of the virus infection is more difficult because the infection of SARS-CoV-2 may be in the lower respiratory track. This proposal takes advantage of our pioneered imaging platformand protein agents to rapid develop pMRI diagnostic imaging with strong translational potential in facilitatingeffective treatment to halt further chronic and pandemic lung disease progression. It is highly transformative andspecifically address the call of proposal for Urgent Supplement using existing imaging modality and MRI andlargely extended its capability. The developed MRI diagnostic imaging with its high resolution, non-radiative, andmuch improved sensitivity than current CT in clinical will significantly facilitate accurate detection of coronavirusinfection in patient and control of Covid-19 and other SARS-like COV infections.",2020,2022,Georgia State University,80860,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2019 +C06972,3K23AG058756-03S2,Sarcopenia as a Predictor of Hospital-Associated Disability in Older Adults,"PROJECT SUMMARY/Abstract: At least half of all physical disability among older adults develops in the setting of an acute hospitalization, andthose with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) are at particular risk forphysical disability after an acute hospitalization. Older adults hospitalized for specific illnesses, such aspneumonia and sepsis, are particularly at risk for developing new physical disability. During the COVID-19pandemic, older adults, compared to younger adults, are also at greater risk of developing more severeCOVID-19, including greater risk of needing to be hospitalized, of requiring ICU admission, and of developingpneumonia and sepsis. As of May 6, 2020, over 3.7 million individuals throughout the world have developedCOVID-19, of which over 258,000 have died. Given the historic scale of the COVID-19 pandemic, theincreased burden of physical disability associated with COVID-19 is very likely to have a vast public healthimpact, particularly among older adults and those with AD/ADRD. However, little is known about the functionaloutcomes of COVID-19, especially among older adults and those with AD/ADRD who are most likely to beadversely affected. Addressing this key knowledge gap is critical in identifying key clinical risk factors foradverse outcomes, informing understanding of pathogenesis of physical disability after COVID-19, andultimately developing interventions to prevent or rehabilitate physical disability in these patients. Thisadministrative supplement proposal is an extension of the existing K23 grant (5K23AG058756-01; ""Sarcopeniaas a Predictor of Hospital Associated Disability in Older Adults""), which was awarded to determine the ability ofsarcopenia, operationalized as muscle mass and strength, to predict the development of activity of daily living(ADL) disability among hospitalized older adults. The additional studies proposed herein will leverage existingresearch infrastructure and experience to conduct an original prospective cohort study (COPE: COVID-19Outcomes in Physical hEalth) that will compare short- and long-term functional outcomes of hospitalization forCOVID-19 between older and younger adults and between those with and without AD/ADRD. These studieswill also identify important pre-hospitalization risk factors (e.g. comorbidities and medication use) for adversefunctional outcomes. We propose to enroll a cohort of 200 survivors of COVID-19 hospitalization (age 65years and older, n=100, of whom n=25 with AD/ADRD; and age 64 years and younger, n=100) and to measurephysical function outcomes (ADLs, frailty, mobility, sarcopenia, Health Assessment Questionnaire (HAQ),fatigue) by telephone interview at 1- and 3-months after hospital discharge. A subset of participants (n=50) willalso undergo in-person assessments of body composition (DXA, ultrasound) and physical performance(muscle strength, Short Physical Performance Battery (SPPB)).",2020,2023,University Of Washington,198244,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2018 +C06973,3P01AG005842-32S2,Improving Health Outcomes for an Aging Population - Project 2,"OTHER PROJECT INFORMATION - Project Summary/AbstractDrug Treatments and the Impact of COVID-19 on Alzheimer's Patients and Other Vulnerable PopulationsInterventions in health policy and care management have the potential to reduce COVID-19 infections anddeaths, particularly if they can be targeted to the most vulnerable populations such as patients with Alzheimer'sDisease and Related Dementias (ADRD). In this supplement proposal, we compile information and develop toolsthat can accelerate and target such interventions. The first aim is to identify the medical and socioeconomiccharacteristics of people that make them most vulnerable to COVID-19. We create cohorts of patients with ADRDand for other vulnerable populations based on their Fall 2019 characteristics, and follow them through 2020 toidentify those at greatest risk of both ""direct"" COVID-19 outcomes (e.g., critical illness, mortality) and ""indirect""increases in non-COVID outcomes. The second aim is an ambitious proof of concept: using natural experimentsto shed light on novel drugs to treat or prevent COVID-19 with a particular focus on drugs most heavily used byADRD patients (e.g., anticholinesterase inhibitors). We will develop and apply a machine learning approach totest the potential effect of drug classes on COVID-19, measured by diagnosis, hospitalization, ICU admission,and death. This supplement is made possible by a unique opportunity: Access to near-real-time Medicare claimsdata (one-month lag), which CMS appears willing to make available through an expedited data use agreement.The application will supplement an ongoing program project on Improving Health Outcome for an AgingPopulation, whose overarching aim is to better understand health trends and disparities, determinants of health,and approaches to improving health for an aging population in an evolving landscape.",2020,2023,National Bureau Of Economic Research,161388,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation",Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Prophylactic use of treatments,1997 +C06974,3K08HD092610-03S1,Impact of COVID-19 on the Mental Health of People with Down Syndrome,"Project Summary COVID-19 is an unprecedented global pandemic. Research from previous large-scale, community traumas(e.g, natural disasters) and epidemics have documented a rise in mental health concerns during such crises,and for some, persisting effects. For families having children with Down syndrome (DS), the effects of COVID-19 may be especially salient due to underlying medical conditions associated with poorer course, fears ofmedical rationing, loss of routines, structure, loss of developmental services, and social isolation. Togetherthese factors create a ""perfect storm"" of risk for depression, anxiety, and behavioral conditions in people withDS that may have long-term consequences for mental and physical health of people with DS. Experts havecalled for surveillance studies to monitor the impact of COVID-19 to inform stepped care so that those athighest risk for psychological sequalae receive needed resources. The original scope of the parent award (K08HD092610) was focused on the assessment and evaluation ofthe associations between exposure to stressful life events, depression, and other markers of mental health inpeople with DS aged 12-45, along with the identification of biomarkers of depression in this population. Thissupplemental project will provide the opportunity to examine the impact of COVID-19-related stressors (e.g.,job loss, social isolation, infection) on the health and wellbeing of caregivers and people with DS, includingmeasures of depression, anxiety, adaptive behavior, and cognitive decline. The specific aims of the project areto: 1) conduct a mental health surveillance study (n = 900) to identify acute COVID-19 pandemic impacts oncaregiver stress and mental health outcomes of people with DS, and to assess their trajectory over time (i.e., 2,4, and 6 month follow up); 2) conduct deep psychiatric phenotyping (e.g., depression, anxiety, cognitivedecline, adaptive functioning) and buccal cell sampling of the people with DS from the surveillance studyreporting the highest (n = 25) and lowest (n = 25) COVID-related stress; and 3) examine acquiredgenetic/chromosomal instability, as measured by DNA methylation, telomere length, and micronucleifrequency, as a mediator between COVID-19 related stress and mental health outcomes. The original scope of the training plan of this career development award was designed to support thecandidate's long-term goal of conducting genomically-informed traumatic stress research in people with DSand other forms of intellectual disability with training in DS-related developmental and psychiatric phenotypes,statistics, and epigenetic biomarkers. An additional mentor, Nicole Baumer, MD, Director of Boston Children'sHospital Down Syndrome Program, has been added to the mentorship team. Dr. Baumer is a leader in theinternational response to COVID-19 in people with Down syndrome (e.g., T21 Research Society COVID-19Survey, Q&A on COVID and Down Syndrome) will bring valuable insight into the consequences of COVID-19infection and pandemic-related stressors experienced by people with DS and their families.",2020,2023,Virginia Commonwealth University,131680,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C06975,3P01AG049665-06S1,Disordered Proteostasis as a Driver of Disease in the Aging Lung,"Pneumonia is the leading cause of death in patients with COVID-19 infection and disproportionately affects olderindividuals. In addition to the diffuse patchy alveolar infiltrates and acute hypoxemic respiratory failure typical ofviral pneumonia, patients with COVID-19 often develop hypotension requiring alpha-adrengergic agonists, veryhigh serum levels of IL-6 and its transcriptional target C-Reactive Protein (CRP) and display evidence ofintravascular coagulation. This is accompanied by the death of cells in multiple tissues including the kidney,muscle, liver and occasionally the heart. This end-organ injury is an important driver of morbidity and perhapsmortality in COVID-19 patients. These unusual clinical features suggest a virus-induced cytokine storm, but theunderlying mechanisms are unknown and these clinical features are not recapitulated in rodent or primatemodels of the disease.Our early analysis of bronchoalveolar lavage fluid collected from the alveolar space ofpatients with severe COVID-19 pneumonia requiring mechanical ventilation challenge the existing paradigm thatIL-6 originates in immune cells within the alveolar space. Specifically, we found that at the time of intubation, thealveolar space in the majority of patients with severe COVID-19-induced ARDS harbors mature alveolarmacrophages and lymphocytes none of which produce IL-6. Instead, a subset of resident alveolar macrophagesproduce IL-1? and appear to support replication of SARS-CoV-2.We hypothesize that disordered proteostasis in alveolar macrophages from aged individuals prevents viral killing after uptake of SARS-CoV-2. Replicating virus activates the inflammasome to induce IL-1? release in the lung, which in turn inducesthe release of IL-6 from endothelial cells in the lung and distant organs. We will test this hypothesis in two relatedexperiments. Experiment 1. To determine whether activation of the inflammasome in response to COVID-19 infection is necessary for the release of IL-6 from the lung endothelium. We will infect lung slices fromnormal human donors with SARS-CoV-2 in the presence or absence of an IL-1? inhibitor that is under evaluationas a therapy for patients with COVID-19 associate pneumonia (canakinumab). We will examine the lung slicesafter infection using single cell RNA-Seq and RNAscope. Experiment 2. To determine whether endothelialcells in tissues outside the lung express IL6 in patients with severe COVID-19. We will perform RNAscopeon fixed tissues harvested from 9 patients who have undergone autopsy after COVID-19 at Northwestern andRNAscope plus single cell RNA-Seq on lung, kidney, spleen and lymph nodes from 5 patients who undergo post-mortem biopsy in our ICU.",2020,2025,Northwestern University At Chicago,317542,Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2015 +C06976,3RF1AG063153-01A1S1,Flexible multivariate models for linking multi-scale connectome and genome data in Alzheimer's disease and related disorders,"Abstract COVID-19 is having a major impact around the world, however we are still learning about the mechanisms and manifestations of this illness. There is considerable evidence of neurologicalsymptoms that occur in COVID-19 patients. However the impact of this, and its relationship withage, on brain structure have not been studies at all thus far. We propose to use multivariate approaches to extract covarying brain patterns from individuals to study changes associated withCOVID-19 as well as potential interactions with age in older individuals. We will leverage the approaches being developed as part of the parent award, but customize them to incorporate spatial priors to address ischemic lesions. We will evaluate COVID-19 and age effects on these networks and compare them with networks extracted from normative data. We will share the methods via user friendly tools. Results are expected to provide insights into the neurological manifestations of COVID-19 including age specific effects.",2020,2024,Georgia State University,143254,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2019 +C06977,3U24AA022002-08S1,Southern HIV and Alcohol Research Consortium Administrative and Research Support Core,"Abstract: It is not clear whether the coronavirus (COVID-19) pandemic has differentially affected HIV outcomes or drinking behavior among rural or ethnic minority populations. Understanding how COVID-19 changes HIV careand alcohol use could strengthen future HIV and alcohol care delivery to increase the resilience of theseprograms. Access to health research is also adversely affected by COVID-19. This shift to telehealth haspotential to help clinicians and researchers connect with hard-to-reach populations. However, we need tounderstand feasibility and acceptability of telehealth by persons living with HIV (PLWH) if we are to extendresearch and improve delivery of alcohol interventions and HIV care in the future. This request issupplementary to U24AA022002, providing supportive infrastructure to the Southern HIV Alcohol ResearchConsortium (SHARC), including the FL Cohort. The objective of the FL Cohort is to better understand barriersand facilitators to viral suppression, focusing on alcohol use. However, the planned FL Cohort will not be ableto distinguish if changes in alcohol use or HIV care are due to COVID-19, and will not have sufficient personsfrom rural or Haitian communities to assess differential effects in these underserved populations. Thissupplement will help determine how COVID-related social isolation and COVID disease have influenced theHIV care continuum, alcohol use and treatment, and acceptance of telehealth, stated interests in NOT-AA-20-011 and high priority HIV research areas. The aims of this supplement are to: 1) Determine the impacts ofCOVID disease and related changes in psychosocial factors (e.g., loneliness, social support, economicinsecurity, domestic violence) on alcohol use and HIV-related care and health outcomes (ART adherence, careengagement, and viral suppression) as assessed before and during social distancing measures; 2) Extend FLCohort recruitment into rural areas and the Haitian community, and compare the psychosocial effects, changesin drinking, and HIV-related outcomes in rural vs. urban settings and within the Haitian community. 3) Assessthe feasibility, acceptability, and interest in remote enrollment and data collection for research, and delivery ofalcohol interventions and HIV clinical care among patients and providers, and compare optimal strategiesacross socio-demographic groups (e.g., age cohort, rural vs. urban, ethnic groups). We will accomplish theseaims by adding an additional COVID-related questionnaire to the existing measures in the parent FLCohort study, recruiting and additional 150 persons from rural areas and the Haitian community whowill complete a single, ""light"" version of the study, and conducting qualitative interviews from PLWHand healthcare personnel to better understand how we can learn from the crisis to adapt newinterventions. The study will have impact by directly informing strategies related to implementation of alcoholand HIV interventions, by expanding our knowledge related to the impact of a new infectious disease pandemicon drinking and HIV outcomes, and by enhancing the overall representativeness of our cohort sample.",2020,2023,University Of Florida,152332,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Community engagement | Indirect health impacts | Social impacts | Health service delivery,2012 +C06978,3R21AG065914-01S1,Neuronal activity modulation and age-related neurodegeneration,"Abstract of proposed studies under the Administrative Supplement in response to NOT-AG-20-022Age is a significant risk factor in the recent SARS-CoV-2 pandemic and this risk might be moreprofound in middle-aged people with age-related cognitive decline, neurodegeneration andAlzheimer's disease. While working directly with the SARS-CoV-2 virus is valuable, it requiresworking in an ABSL-3 level facility and substantially restricts potential behavioral and cognitivestudies, brain imaging experiments, and postmortem studies with non-perfused tissues. SARS-CoV-2 recombinant virus-like particles (VLPs) offer an attractive way to study the pathogenesisof SARS-CoV-2 in animals, without the involvement of replicating viruses. In this study, we exposewild-type and human tau mice to SARS-CoV-2 VLPs to study the effects on cognitiveperformance, brain activity, markers of inflammation, and the effect of sex on the expecteddegeneration. This study will provide the first data on potential central nervous systemcomplications of Alzheimer's disease patients, as well as an age-matched population, which areexposed to SARS-CoV-2 VLPs, and will provide an experimental platform to test potentialtreatments.",2020,2022,Cleveland Clinic Lerner Com-Cwru,250383,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C06979,3UL1TR002369-04S3,Oregon Clinical and Translational Research Institute - Evaluation of OCTRI's Response to COVID-19,"The Oregon Clinical and Translational Research Institute (OCTRI) has been accelerating research at OregonHealth & Science University since 2006. Its many highly functional programs assist investigators and traineesby providing diverse services. Here, we propose that OCTRI will transition to retain our strengths, but alsobecome a key hub in the national network, by focusing on five crosscutting aims. These align closely with thegoals of the Funding Opportunity Announcement, and the goals outlined by NCATS for the CTSA program inan ideal state. OCTRI's overall aims are to:Overall Aim 1: Catalyze Clinical and Translational Research.Overall Aim 2: Enhance Partnerships with Communities.Overall Aim 3: Foster and Support Scientific Collaboration.Overall Aim 4: Expand the Translational Workforce for the 21st Century.Overall Aim 5: Cultivate Innovation in Research.We have organized a highly functional leadership structure to enable us to meet these goals, and will seek theguidance of several advisory groups. We will catalyze research by developing and supporting new informaticsapproaches that both integrate the clinical care enterprise with the research enterprise and facilitate therecruitment of patients into clinical trials, locally and across the CTSA network. We will engage diversestakeholders in the translational research process, by partnering with OHSU investigators, communitycoalitions, and business enterprises. We will foster team science through local awards to trainees and toemerging investigators. We will partner with regional institutions to foster community-engaged research, toenhance the diversity of trainees, and to provide opportunities in biomedical research not available at otherinstitutions. We will train clinical and translational scientists and research staff for the next generation, byfocusing on the skills and attitudes necessary for research in the future. At all steps, we will measure outcomesand, when necessary, ""turn the curve.""",2020,2022,Oregon Health & Science University,93496,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Health service delivery | Health leadership and governance,2017 +C06980,3P42ES031007-01S1,The UNC Chapel Hill Superfund Research Program (UNC-SRP) (1),"Abstract: The Data Management and Analysis Core (DMAC) provides critical support for University of North Carolina(UNC)-Superfund Research Program (SRP) researchers to manage and analyze data related to the theme,""Identifying novel methods to reduce inorganic arsenic (iAs) exposure and elucidating mechanisms underlyingiAs-induced metabolic dysfunction with a vision for disease prevention."" Across the globe and in the UnitedStates, there is an urgent need to identify the factors that increase susceptibility to the severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease (COVID-19) and interventions to reducedisease. We propose herein a study which will begin to address some of these questions as well as build capacityto answer further questions regarding environmental contributions to viral-induced disease. In thisadministrative supplement, we build upon the activities in the DMAC and propose to address the fundamentalknowledge gap in understanding environmental contributions to the COVID-19 burden in both NC and the USmore generally as well as build tools to address these questions. In NC, communities are at risk of exposure totoxic substances known to affect the immune system. As an example, with millions of individuals on private wellsin NC, there is significant concern that communities are exposed to toxic levels of inorganic arsenic (iAs), aknown immunosuppressant. In addition to exposure to these chemical toxicants, communities are faced withexposure to social stressors such as neighborhood violence, unemployment, and poverty. These social stressorshave also been shown to have physiologic effects on the immune system. Additionally, the synergistic effects ofchemical and social stressors is becoming increasingly clear. These combined exposures may disproportionatelyimpact the health of individuals who have reduced immune system function such as those suffering with obesity,those with chronic medical conditions, and the elderly. As a major output of this study, we propose thedevelopment of the NC Environmental Scan web portal (NC ENVIRO-SCAN) that will integrate key datasets ofiAs, social stressors, and COVID-19 information to be able to identify communities with increased risk of infectionand disease outcome. The central hypothesis of this research is that individuals living in areas whereexposure to iAs and social stressors are high will have increased COVID-19 disease burden. Thishypothesis is based on findings in our laboratories as well as the published literature. The three aims in thesupplement include: (1) Evaluate the association between exposure to iAs, social stressors and COVID-19disease risk in NC; (2) Identify resiliency factors that protect against COVID-19 disease risk; (3) Develop the NCENVIRO-SCAN web portal and disseminate results to key stakeholders in NC. This study is novel in itsinvestigation of combined effects of toxic substances (iAs), social stressors, and COVID-19 disease risk. It hasthe potential to improve public health in NC and protect populations from the harms of chemically-enhanceddisease risk.",2020,2021,University of North Carolina at Chapel Hill,457296,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Infection prevention and control,"Disease susceptibility | Barriers, PPE, environmental, animal and vector control measures",2020 +C06981,3R00AG053412-04S1,Neurotropic Viral Infection in CNS Aging and Alzheimer's Disease COVID-19 Supplement,"Project Summary: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and itsresulting disease (COVID-19) emerged as an unprecedented worldwide healthcare crisis. COVID-19 primarilymanifests as a lower respiratory tract infection and viral pneumonia; however, neurotropism is a commonfeature of coronaviruses (CoVs) and has been documented for almost all betacoronaviruses, the clade towhich SARS-CoV-2 belongs. It was reported that 36% of COVID-19 patients develop neurologic symptoms,but whether these are due to CNS infection, systemic inflammatory response, or intensive care unit delirium isunknown. Advanced age is a significant risk factor for developing severe infection from SARS-CoV-2. Aging isassociated with compromised cellular immunity and blood brain barrier dysfunction, which may increase thevulnerability of the CNS to infection and long-term damage from systemic infections. Neuroinflammation isrecognized as contributing to disorders of the central nervous system (CNS) including Alzheimer's disease(AD). Our overarching hypothesis is that viral encephalitis enhances inflammatory events that accelerate CNSaging processes and contribute to the development of AD pathology. The original application proposed to useWest Nile virus (WNV) as a model of viral encephalitis to examine behavioral, cellular, and molecularmechanisms of CNS recovery. Here we propose to enhance this research by investigating a murine CoVmodel, mouse hepatitis virus A-59. Like WNV, CoVs are enveloped positive-stranded RNA viruses, but havedistinct effects in the CNS. The addition of this CoV model will augment the original scope of the proposal byallowing the comparison of results from each of the two models to determine universal aging processes thatresult from viral infection. In this supplement, we propose to test the hypothesis that advanced age increasesthe risk of lethal neurotropic infection by CoV and that inflammatory processes initiated by infection maycontribute to the pathogenesis of AD. Aim 1 will determine the impact of advanced age on acute viral infectionand antiviral response. Aim 2 will identify the effect of advanced age on microglial response to infection. Aim 3will investigate the impact of viral encephalitis on pathological Tau accumulation. These studies will addressthe urgent need to understand how aging impacts CoV infections, the impact of viral encephalitis on agingprocesses in the CNS, and their contribution to neurodegenerative diseases. The experiments proposed herewill be analyzed in parallel with our established model of WNV to enhance the goals of the original proposal.",2020,2022,University Of North Carolina Charlotte,243918,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2019 +C06982,3P30AG064200-02S1,Roybal Translational Research Center to Promote Context-Specific Caregiving of Community-Dwelling Persons Living with Alzheimer's Disease or Related Disorders,"Abstract. This application seeks support for an administrative supplement to the Emory Roybal Center forDementia Caregiving Mastery (P30AG06400). We seek to develop and test a broadly accessible and readilyscalable online fully asynchronous course for family caregivers of community-dwelling persons living withdementing disorders like Alzheimer's disease to prepare them to master the new demands of their caregivingrole in the extraordinary circumstance of the coronavirus (COVID-19) pandemic. Under normal circumstances,caregivers need to learn how to guide their person through safe, calm, and pleasant days. In a time of COVID-19, caregivers have to learn how to take all of the complicated precautions to keep themselves and theirpersons from being exposed to the virus. They need skills for keeping their persons occupied and calm in a""shelter in place"" world where day programs or other regular outings to large group settings (e.g., places ofworship) are unavailable. And they need skills for navigating the healthcare system to manage their person'shealth in ways that minimize the need to use emergency or acute services. We seek to produce an onlinecourse that can be completed in 4-6 weeks that will develop and enhance caregivers' mastery not only toprovide effective day-to-day care guidance, but to ensure their care recipients' health and safety, and tofunction as healthcare system navigators for their care recipients. The course will engage caregivers in self-paced learning in a format tailored to and calibrated for a lay learning audience. It will be structured as a smallgroup ""class,"" of 20-30 participants who will interact virtually but never meet as a group, and whose activitiesand exercises will be monitored by a course faculty member. In our Aim 1 activities, we propose to develop, incollaboration with an educational design consultant team, the online course designed to teach these skills. Theproject will seek input from caregivers, clinicians, and other experts - and used the Roybal Center's DesignStudio capacity - to develop the structure, content, and ""feel"" of the course and produce a testable prototype.In our Aim 2 activities, we will recruit 100 family caregivers to take part in a quantitative and qualitative wait-listcontrol randomized trial of the prototype course. The trial will assess usability and acceptability and it will besufficiently powered to examine the preliminary efficacy of the course to develop caregiving mastery andbenefit caregivers' well-being. Formative evaluation data, course faculty observation, and course use data willbe used to produce a revised version of the course. MPIs Hepburn and Clevenger bring psychoeducation andcontinuing education program development experience and extensive clinical and caregiver expertise to theproject - and an established working relationship with the educational consulting team. The Aim 2 test willprovide the basis for an application for a larger randomized trial through an R01 mechanism. The results of theAim 2 test will also support making the course more widely available through reliable channels that can provideappropriate course supervision, such as the NIA-supported Alzheimer's Disease Centers.",2020,2024,Emory University,281998,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management | Research on Capacity Strengthening,"Supportive care, processes of care and management | Individual level capacity strengthening",2019 +C06983,3R01HG004483-12S1,Web-based visualization of coronavirus genomes and proteins,"Project Summary: This supplemental proposal knits together several bioinformaticsvisualization tools in the service of SARS-CoV-2 genome analysis.The core of the proposal is a newly-prototyped JavaScript viewer,ABrowse, that is capable of rendering multiple sequence alignments,navigable by phylogenetic trees, and integrated with protein structureviews, all in a single embeddable component. The ABrowse viewer iscurrently employed to render the Pfam SARS-CoV-2 special release:a collection of 40 protein domains from the coronavirus genome, alongwith PDB structures. (ABrowse is also a candidate for Pfam's futuredefault viewer, as noted in the letters of support.)We propose to accelerate ABrowse development for use by theCOVID-19 pandemic, specifically targeting scaling, performance, andintegration issues that are most relevant to scientists studying thevirus. Chief amongst these is scaling ABrowse to handle millions ofprotein sequences (and/or SARS-CoV-2 genome sequences) bymeans of a new, compressed storage format suitable forrandom-access user-driven exploration of very large trees (andalignments) over the web.Beyond scaling, we also address integration, developing plugins forABrowse to run within JBrowse (the genome browser that is the focusof the project to which this is a supplemental proposal) as well asAuspice (the web dashboard of NextStrain, the phylogenetic genomealignment and annotation package that is widely used for COVID-19analysis). We also propose several user interface enhancements tomake ABrowse more useful as a navigation tool for COVID-19 data.",2020,2021,University Of California-Berkeley,354767,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C06984,3R01AG062282-03S1,COVID-19 and Acute Medical Care: Impact on Dementia Patients,"Abstract.The SARS-CoV-2 virus has resulted in hundreds of thousands of deaths across the globe andoverwhelmed many health systems. In Massachusetts alone, there have been over fivethousand deaths over a two month period attributable directly to COVID-19, i.e., the diseaseresulting from viral infection. Lacking a vaccine or definitive treatment, slowing disease spreadsuch that daily demand falls within the capacity of local medical systems is the immediatepriority for this outbreak, but the changes involved with such mitigation efforts could be costly.For example, many hospitals have implemented changes to increase capacity for COVID-19patients, e.g., delaying elective procedures and shifting resources across service lines, whichcould impact care for other conditions requiring time-sensitive care, e.g., strokes or heartattacks. There currently is limited information on the impact of the outbreak on non-infection,acute medical conditions. There also is little information on how hospital responses impactpatient outcomes. Given concerns about future outbreaks in other states, as well as additionalrepeat outbreaks (or waves of disease transmission), there is a critical need for these types ofinformation. In this project, we will address two aims: 1) to examine the impact of the COVID-19demand shock on acute medical care received in the Emergency Department (ED) or hospital;and 2) to examine hospital responses to the demand shock and their impact on clinical eventrates. We will use novel, linked real-time data sources to address these questions overall andfor vulnerable population subgroups such as patient with dementia. Indeed, the early reportssuggest that the elderly are disproportionally affected by COVID-19 itself and potentially thehealth system's changes in response to the outbreak. These data could inform preparation forfuture COVID-19 outbreak waves occurring later this year, as well as future transmissibledisease outbreaks.",2020,2023,Massachusetts General Hospital,654203,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C06985,3R01AG060581-03S1,COVID-19 Supplement to Strategic Approach to Facilitating Evacuation by Health Assessment of Vulnerable Elderly in Nursing Homes II (SAFE HAVEN II),"PROJECT SUMMARY/Abstract: Much of the research concerning the effect of disasters on older adults has focused on weather events andother natural disasters. The COVID-19 emergency provides critical evidence of the need for an all-hazardsapproach that includes more robust planning for pandemics. Currently, nursing homes (NHs) and assistedliving communities (ALCs) face a mounting challenge from the COVID-19 virus. The reports of NH deathsraise the prospect that the 1.3 million NH residents will be among the most severely affected population. Therisk is also believed to be high for ALC residents, where acuity has increased in the past decade. Of criticalconcern is the care of residents with Alzheimer's disease and/or related dementias (ADRD), who make up 50%of NH residents and 41% of ALC residents. Residents living with ADRD are potentially at great risk of harmfrom COVID-19 because of difficulty they may have understanding safety precautions (e.g. social distancing)and the trauma of usual care disruptions. We propose to supplement our current research into the effects ofHurricanes Harvey (Texas) and Irma (Florida) by examining the effect of and response to the COVID-19emergency among NHs and ALCs in Florida, with a focus on residents with ADRD. The overall goal of ourcurrent research, SAFE HAVEN II, is to understand more about the effect of hurricanes on older adults inresidential care. It conceptualizes disaster planning within the all-hazards framework. The Centers forMedicare and Medicaid Services requires all US NHs to develop all-hazards disaster plans that includepreparedness for a pandemic. However, NH and ALC responses to the COVID-19 emergency suggest a greatneed for guidance concerning protecting residents and staff, maintaining staff, and managing stress caused bysocial distancing requirements and other disruptions. This supplement proposal builds on the parentapplication by employing the research infrastructure established for SAFE HAVEN II, including relationshipswith NHs and ALCs across Florida. Through this supplement, we propose a mixed methods approach tosurvey and interview NH and ALC administrators to better understand the impact of the COVID-19 emergencyon their ADRD residents compared to other residents without ADRD (Aim1), and to define the morbidity andmortality of NH and ALC residents and how this varies for residents with ADRD vs. those without (Aim 2). Aim1 results will be used to provide critical initial guidance on protecting residents from COVID-19 and additionallyto generate hypotheses concerning the effect of and response to the virus in long-term care. Quantitative datacollected and analyzed through Aim 2 will be used to test these hypotheses and confirm or refine guidancefrom the qualitative analysis. These results, combined with work from the parent project, have the potential tosubstantially strengthen the ability of NHs and ALCs to protect and care for their most vulnerable residents.Results will provide valuable guidance concerning residents with ADRD, potentially at greater risk of harm in apandemic due to exposure, disruptions, and isolation.",2020,2021,University Of South Florida,409217,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Approaches to public health interventions | Indirect health impacts,2018 +C06986,3RF1AG054442-02S6,"Brain atrophy, cognitive impairment and Alzheimer's in low CVD-risk population","Project Summary: The parent RF1 (1 RF1 AG054442-01) provides new data on brain atrophy and Alzheimer'sdisease and Related Dementias (ADRD) in two indigenous Bolivian populations, the Tsimaneand the Moseten, with extremely low rates of cardiovascular disease (CVD) but high burdens ofinfection and inflammation. The aims of this project are: (1) Longitudinal assessment ofcognitive impairment and dementia in a low cardiovascular disease (CVD) risk population,Tsimane forager-horticulturalists of lowland Bolivia; (2) Neuroimaging to identify brain atrophycorrelates of cognitive impairment, AD and other dementias; (3) Characterization of theprevalence of brain atrophy, cognitive impairment, and dementias in the Tsimane; (4) Collect in-depth data on diet and physical activity; and (5) Examine the interaction of inflammation andAPOE genotype on cognitive functioning for individual longitudinal change. ADRD prevalencewas estimated during the first 2.5 years of NIA funding. Current results indicate a lowprevalence (<5%) of dementia after age 70 with no cases of moderate to severe dementia. Thetwo specific aims of this administrative supplement will determine: (1) whether cognitiveimpairment and dementia are risk factors for SARS-CoV-2 infection and/or morbidity andmortality, if infected; and (2) if Covid-19 results cognitive and neurological aging impairment.The first aim is necessary for interpreting existing data and achieving the original project goals.it is necessary to determine whether those who develop cognitive impairment dementia are atgreater risk for COVID-19 mortality in order to control for a potential downward bias in theestimation of dementia incidence. The second aim presents a new unique opportunity toinvestigate the original project goal of studying impacts of infection on cognitive decline andADRD. It will evaluate the impact of COVID-19 infection on cognitive function and ADRDincidence.",2020,2022,Chapman University,1035885,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts,2017 +C06987,3R00AG052604-04S1,Epigenetic Age Measures to Predict COVID-19 Symptom Progression and Severity,"PROJECT SUMMARY The risk of fatality and/or severe complications due to COVID-19 infection is strongly agedependent. Data from the CDC suggests that those ages 85 and older have predicted mortality ratesthat is 100-fold higher than for those under the age of 50 and currently, 8 out of 10 COVID-19 deathsin the United States were in adults age 65 or older. While the exact etiology underlying this agedisparity is unknown, evidence suggests that vulnerability may be due to changes that occur as afunction of the aging process. This is further evidenced by the pattern of increased vulnerabilityamong persons with pre-existing diseases of aging-cardiovascular disease, diabetes, COPD,chronic kidney disease, liver disease-suggesting that it isn't just chronological age that determinesrisk, but rather, biological age. In recent years, our group has helped develop some of the most robust biomarkers available,namely the epigenetic clocks. These measures estimate biological age in a sample based on DNAmethylation levels at hundreds to thousands of CpG sites across the genome. Not only do epigeneticclocks track with age in diverse tissues and cell types, but discrepancies between epigenetic age andactual age have also been shown to predict risk of mortality and incidence of major chronic disease,including those which appear to be major risk factors for COVID-19. However, in order for thesemeasures to be informative for assessing COVID-19 risk clinically, or in the general population, 1)they need to be re-optimized to capture the aspects of biological aging specific to COVID-19susceptibility, and 2) advances in technology need to be made to ensure lower costs and rapidturnaround. This proposal aims to build on our team's multidisciplinary strengths to develop and validate atargeted, lab-developed, readily-available test to predict COVID-19 symptomology and mortality risk.If successful, this test will have widespread applications-from informing triage and treatmentdecisions in the clinic, to guiding social and pollical decisions when it comes to lifting ""stay-at-home""orders for certain individuals.",2020,2021,Yale University,139448,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2017 +C06988,3R01AG061105-03S1,A knowledge map to find Alzheimer's disease drugs,"ABSTRACT. This Supplement extends Aims 1 and 2 of the parent grant on Alzheimer's Disease (AD) bydeveloping: prospective benchmarks for algorithms that predict biomarkers of disease risk (Aim 1) and newalgorithms to support drug repositioning (Aim 2). Both extensions strengthen Aims 1 and 2 for AD but also haveimmediate applications for research on COVID-19 disease in keeping with NOT-AG-20-022.AIM 1 of the parent grant develops EA-ML, a Machine Learning (ML) pipeline to compare coding mutations inindividuals with and without AD. The output is a list of genes with which to predict AD risk from their mutations.While the parent grant has multiple criteria for success, none are prospective given the vast lead-time betweenAD onset and symptoms. Supplemental Aim 1 adds prospective testing, using COVID-19. This is possiblebecause the UK Biobank has begun to annotate its 50,000 public exomes with the COVID-19 status ofindividuals, including who had severe morbidity or mild symptoms at worst. The biobank will also add 150,000more exomes by end 2020. Accordingly, we will apply EA-ML to the current UK biobank data to identify humangenetic biomarkers that distinguish severe from mild cases and then test EA-ML predictions of COVID-19virulence prospectively, on the exomes that are newly added to the biobank. As a further new benchmark, wewill also compare EA-ML to a novel ""EA-Wavelet"" algorithm, also tested prospectively on COVID-19. EA-Wavelet sorts cases from controls by factoring EA over the entire network of human protein-protein interactions.The results will tell us which of EA-ML, EA-Wavelet, or combination thereof is the best at identifyingcritical biomarkers and clinical risk of AD, while also doing the same for COVID-19.Aim 2 of the parent grant develops drug repositioning for AD by linking target genes and drugs via knowledgemaps of functional interactions. Here, we propose a complementary approach that connect genes to drugsvia structural maps of binding epitopes. For this we will comprehensively map evolutionarily important sitesin the structural proteome of genes that are associated with AD. The approach exploits EA theory to measurepast and present evolutionary forces in fitness landscapes, and it takes into account current sequence variationsto guard against any possible mutational escape from drugs that target these epitopes. The output will be surfaceaccessible regions of proteins that can then be used for (i) computational docking of small molecules towardsdrug repurposing, combination therapy, and lead discovery for drug design3-5; (ii) engineering mimetic peptidesor other molecules that can inhibit normal interactions6; and (iii) CRISPR engineering or peptide synthesis thatcreate antigens for more effective vaccines7, 8. These automated mapping tools are general, and besides inSARS-CoV-2, will identify an entire new structural library of functional sites to target for AD therapy withrepurposed drugs.",2020,2023,Baylor College Of Medicine,386555,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation",Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies,2018 +C06989,3R44AA025804-03S1,Novel modulators of the dopamine transporter for alcohol and nicotine use disorders,"Abstract: The parent award is to develop novel medications for alcohol and nicotine use disorders. Thesedisorders have increased during COVID19 [e.g. Clay and Parker 2020] and are associated withincreased susceptibility to, and severity of, infection. This supplemental proposal is focused onhow mechanisms of COVID-19 infection and neurotoxicity are influenced by alcohol and nicotine,and how these novel medications interact with these mechanisms. The applicants have previouslyused organotypic hippocampal neuronal cultures to study interactions between nicotine, alcoholwithdrawal and viral protein neurotoxicity, and these cultures will be used here. First, nicotine hasbeen reported to up-regulate the viral ""receptor"" angiotensin converting enzyme 2 (ACE2) onneurons, providing a mechanism for increased SARS CoV2 infectivity and neurotoxicity insmokers and ""vapers"" [see Kabbani & Olds 2020]. The nicotinic receptor partial agonists(lobinaline N-oxides) from the parent award should inhibit this effect of nicotine, and this will betested in the first specific aim using immunohistochemistry to evaluate ACE2 expression inorganotypic cultures. Once CNS infection has occurred, coronaviruses cause ""excitotoxicity"" thatis inhibited by inhibitors of neuronal glutamate /NMDA receptors (NMDARs) [Hasanagic &Serdeveric, 2020]. This is similar to alcohol withdrawal (AWD) [Stepanyan et al, 2008] and soshould be ameliorated by drugs that prevent neurotoxicity in AWD. Once again, the nicotinicactivity of lobinaline N-oxides may be valuable, but another medication under development by thecompany for alcohol use disorder, the aryliminoguanidine, JR220, is even more directly relevantbecause it is an inhibitory modulator of the NMDAR [Barron et al, 2012], The neuroprotectivepossibilities for these drugs will be evaluated against viral protein neurotoxicity in organotypiccultures in specific aim 2. The hypothesis is therefore that coronavirus infectivity and neurotoxicityare enhanced in patients with nicotine and alcohol use disorders, and that both the disorders andthe COVID19 consequences should be inhibited by the medications under development. Thesenovel therapeutic targets for lobinaline N-oxides and JR220 in COVID-19 infection will stronglysupport the therapeutic and commercial value of products from the parent award.",2020,2023,Naprogenix Inc,140059,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Prognostic factors for disease severity | Supportive care, processes of care and management | Prophylactic use of treatments",2016 +C06990,3P30CA225520-03S5,Stephenson Cancer Center - Cancer Center Support Grant,"The COVID-19 pandemic has profoundly altered nearly every facet of daily life. Although social and physicaldistancing constraints appear to be slowing the spread of the disease, they may be adversely affecting cancer-related preventive behaviors and accessibility to medical services, including cancer treatment. The impact ofsuch COVID-19 restrictions must be quantified to understand and mitigate short- and long-term effects acrossthe cancer continuum, especially among vulnerable populations, including American Indian adults. The goal ofthis study is to explore how differences in demographics (e.g., age, sex, educational attainment) may impactengagement in cancer preventive behaviors (e.g., tobacco cessation, cancer screening) and cancermanagement/survivorship behaviors (e.g., access to cancer treatment services) in the context of COVID-19restrictions (e.g., social distancing, alterations in work arrangements) by surveying a sample of 1,000 AmericanIndian adults, including those who have never had cancer, cancer patients and cancer survivors. This study willbe conducted by the Stephenson Cancer Center Community Outreach and Engagement (COE) program inclose coordination with three American Indian tribal nations, Choctaw Nation of Oklahoma, Chickasaw Nation,and Cherokee Nation, and the Oklahoma Area Tribal Epidemiology Center. This goal will be achieved bycompleting three specific aims: (1) to develop and administer a survey exploring the impact of COVID-19restrictions on cancer prevention and control behaviors. This survey will include a core set of common dataelements that will be administered by several NCI-designated Cancer Centers to increase the depth andgeneralizability of findings; (2) to develop an accurate and robust data integration method using novel machinelearning and propensity score weighting approaches to improve the representativeness of the sample ofAmerican Indian adults that will be drawn in Oklahoma; and (3) to analyze data to inform tribes, healthcaredelivery systems serving American Indian patients, and Stephenson Cancer Center research programmembers and clinicians regarding how American Indian adults are being impacted by the COVID-19 pandemic.Findings will be used to inform interventions and policies aimed at mitigating the cancer-relevant effects ofCOVID-19 restrictions in a highly vulnerable group residing within the Stephenson Cancer Center catchmentarea of Oklahoma. Future iterations of the survey to monitor trends over time are planned. A timeline ofCOVID-19 related guidance, restrictions or regulatory mandates that have been enacted at the national, stateand tribal levels will be constructed to form a context that will allow for meaningful interpretation of findings bytribal community leaders and researchers.",2020,2023,University Of Oklahoma Hlth Sciences Ctr,145000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C06991,3U01HG011166-01S1,The Electronic Medical Records and Genomics (eMERGE) Network Phase III - Coordinating Center (U01),"As the COVID-19 pandemic emerged in early 2020 and rapidly spread across the US, an urgentneed developed to improve our current understanding of what factors increase infection risk,likelihood of severe illness, or poor outcomes. Early reports suggest genetics, personal healthhistory, socioeconomic factors, and one's environment increases risk of infection or differencesin outcomes, but little is known with high confidence. As there are currently no vaccinations orother preventative treatment, understanding clinical and genetic risk factors would immediatelyimprove our ability to manage the pandemic across populations and deliver precision care at thebedside. The Electronic Medical Records and Genomics (eMERGE) Network has the expertiseand resources to investigate the factors leading to increased COVID disease susceptibility byrapidly compiling data from electronic health records (EHRs) and mining records for gene anddisease associations. To perform this task well, the features of COVID disease course andcharacteristics of patients with COVID-19 and those who serve as controls must be preciselydefined (""ePhenotyped"") across different record system. Our experience with phenotyping andimputing genomic and EHR data across large populations will enable us to quickly merge alarge number of COVID-19 patients for future genome and phenome wide association studies,polygenic risk assessments, and candidate gene studies. Our specific aims include first tocreate and deploy ePhenotypes for immediate research use establishing a COVID casedefinition, severity scale, and comorbidities with relation to outcomes. Secondly, we propose tocollect COVID EHR and genomic data centrally for future translational research. Theseresources will be beneficial to the scientific community, necessary to predict comprehensive riskof disease across the lifespan, and have the potential to impact downstream patient care.",2020,2021,Vanderbilt University Medical Center,900400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +C06992,3R01AG051588-06S1,Nighttime Agitation and Restless Legs Syndrome in People with Alzheimer's Disease,"Summary/Abstract. Factors associated with Covid-19 social distancing - such as isolation from family, restrictedmovement, insufficient sunlight and social and physical activity, lack of caregiver supportservices, and caregiver exhaustion - may adversely impact the well-being of older adults withAlzheimer's disease related dementia. Because older adults with dementia are cognitively andverbally unable to express their distress, and both sunlight and activity are necessary for healthysleep patterns, social distancing may increase agitation behaviors, worsen sleep patterns, andincrease prescriptions for antipsychotics and sedating medications to manage these problems. We propose an Administrative Supplement to the NightRest study, R01AG051588, todetermine the impact of social distancing on the well-being of older adults with Alzheimer'sdisease related dementia. The primary specific aim is to determine the impact of socialdistancing on nighttime agitation and sleep. The hypothesis is: social distancing will result inmore nighttime agitation and less sleep. Aim 2 will explore the impact of social distancing onphysical function and use of antipsychotics and other sedating medications. Aim 3 will explorethe impact of social distancing from the perspectives of family caregivers using qualitativeinterviews and a Facebook survey. The research will employ an observational study design.Participants from the NightRest trial, 50 pre- and 50 post-Covid-19, living independently or innursing homes, matched on relevant variables, will be used for Aims 1 and 2. Content analysisof 30 family caregiver qualitative interviews (Aim 3) will result in a list of priorities to minimize theimpact of social distancing. Family caregivers accessed via a Facebook survey will rank andadd to the priorities. Because the NightRest study team possesses pre-Covid-19 data, has access to familycaregivers who have expressed interest in future studies, and has developed and piloted virtualdata collection methods, we are uniquely positioned to determine the impact of Covid-19 socialdistancing policies on well-being. We also have the ability and the networks to translate thefindings. The results will be widely disseminated in November/December, 2020 to stakeholdersand other policy influencers through social media, press releases, and presentations. Theproposed project may result in more tailored social distancing policies in the future. Further,dissemination of nursing home realities to a world closely following Covid-19 developments mayultimately result in better nursing home care, not just for now, but also in the future.",2020,2021,"University Of Texas, Austin",531481,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C06993,3K01AA025692-03S1,Functional relations between alcohol use and mental/physical health in the wake of the COVID-19 pandemic,"Project Summary Beyond the impact of infection itself, the COVID-19 pandemic has resulted in far-reaching effects onbehavioral, social, psychiatric, and substance use outcomes. Early data has documented increases in alcoholuse in the wake of the pandemic, consistent with prior evidence of increased alcohol consumption during timesof stress and following traumatic events. Immediate and downstream implications of increased alcohol use, anddevelopment of alcohol use disorder (AUD), on public health include the interplay between alcohol use andpsychiatric distress (i.e., posttraumatic stress disorder; PTSD), potential for problematic alcohol use to increasebehavioral risk for infection/transmission of COVID-19, and the possibility that weakened immune systems andhealth conditions associated with AUD may impact disease severity in those who develop COVID-19. Theoverarching goals of this K01 Supplement are twofold. First, this supplement aims to extend the PI's training toincorporate health impacts of AUD and how it relates to COVID-19 risk and severity, along with analytic trainingin longitudinal modeling and methodological training in an intensive time-series data collection method to try anddevelop a mechanistic understanding of the functional relations between alcohol use, PTSD, risky behaviors,and health outcomes. Second, two new research aims associated with these training aims were added whichseek to address gaps in the current stress and alcohol use literature by leveraging an existing, longitudinaldataset, with prospective (i.e., pre-pandemic) data. The two new research aims are to 1) assess the immediate,and trajectory of, COVID-19 impacts on alcohol phenotypes (e.g., consumption, binge drinking, problems) incomparison to pre-pandemic data and 2) in the context of COVID-19 as an ongoing stressor, collect repeated,time-series data to examine the temporal relations between alcohol phenotypes, PTSD, and COVID-specificrisky behaviors (e.g., lack of social distancing). To achieve these training and research aims, an additional mentorwith expertise in both the health impact of AUD and COVID-19 treatment trials has been added to themultidisciplinary mentorship team. Further, the PI's primary K01 mentor has specific expertise in theimplementation of COVID-19 surveys on substance and mental health outcomes and experience with time-seriesdata collection in traumatic stress populations. The proposed research represents an important contributiontowards advancing our understanding of the complicated interrelationship between AUD, PTSD, and riskybehaviors in the context of the COVID-19 pandemic to determine not only who is at risk, but when risk behaviorsoccur. This information will be important for attempts to plan for a public health response during and after thepandemic. Under the umbrella of a career development award, this pilot data will inform future large-scale studiesand R-level grants aimed at identification and prevention of COVID-19-related impact, further positioning the PIto continue this line of work by adapting ongoing training to be responsive to medical pandemics and decreasethe burden of alcohol-related problems, consistent with NIAAA research priority.",2020,2023,Virginia Commonwealth University,55408,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C06994,3R01NS106229-02S2,Resolving SARS-Cov-2 tropism and COVID19 pathology in the brain,"SUMMARYCoronavirus disease 2019 (COVID19), caused by severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2), has emerged as a global pandemic, causing overwhelmingmorbidity and mortality. While the main manifestations of COVID19 relate to problems withrespiration, emerging studies recognize the presence of neurological complications in a numberof patients, so far primarily related to cerebrovascular disease as reported by our group andothers. Urgent high-resolution molecular studies are needed to understand better how theSARS-Cov-2 coronavirus targets the brain and whether its effects on the cerebral vasculatureare through direct infection, secondary systemic coagulopathy, or a combination of both, whichcarries specific implications for future risk stratification and treatment in vulnerable individuals.The purpose of this one-year supplement is to urgently elucidate the cell-type specific tropism ofthe SARS-CoV-2 virus in primary COVID19 autopsy brain tissue using complementary singlecell transcriptomic and histological analysis tools already established by our team, and toelucidate further the cellular and molecular associations between viral infectivity, co-expressionof ACE2 and other putative viral receptor targets, and central nervous system pathology relatedto cerebrovascular disease, other pathophysiological manifestations of COVID19, and pre-existent co-morbidities. A better understanding of COVID19 pathophysiology in the brainthrough this and other studies will inform clinicians of more effective and personalized treatmentprotocols for patients infected with SARS-Cov-2 who may be predisposed to having neurologicalcomplications.",2020,2023,Icahn School Of Medicine At Mount Sinai,339000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C06995,3R01HD090180-05S1,Genetic-epigenetic and aging interactions at COVID- 19 host response loci in Down syndrome and mouse models,"The importance of the COVID-19 pandemic, with >3M cases and >130K deaths in the USA alone, cannot beoverstated. This highly contagious and too often lethal infection with SARS-CoV-2 has both severe acuteeffects and longer-term adverse sequelae, and disease severity and death rates are strikingly higher in elderlyindividuals. Pathogenesis and host responses to COVID-19 are still very much under investigation, but initialhypotheses include roles for host cytokines, including pro-inflammatory IL-6 and Type I and III interferons(IFNs), and S100-family proteins. Importantly, a group of IFN pathway genes are triplicated in people withDown syndrome (DS; trisomy 21), and other COVID-19 relevant genes, including S100B and TMPRSS2 arealso on chromosome 21. In addition, investigators seeking drug targets have pointed out the dependence ofthe virus on the methyl donor (folate pathway; S-adenosylmethionine; SAM) status of host cells, and a group ofgenes in this pathway are triplicated in DS. From research on COVID-19 in the general population, the geneticbackground of the infected host is known to be important, with a Genome Wide Association Study (GWAS)revealing significant associations with single nucleotide polymorphism rs11385942 in chromosome band 3p21and rs657152 at 9q34. At locus 3p21, the association signal spans the genes SLC6A20, LZTFL1, CCR9,FYCO1, CXCR6 and XCR1, and it is not yet clear which is the most important gene, and which is the criticalgenetic variant. How the presence of the extra chromosome 21 in DS might affect this important locus is acritical issue, and we have preliminary data pointing to differences in DNA methylation in this region in DS vs.control individuals. Importantly, an accurate mouse model of COVID-19 in the DS genetic background isneeded but has not yet been developed. Given these challenges, here we propose to localize COVID-19related host genomic sequences that are epigenetically regulated and altered in immune cell types from DS vseuploid individuals, to use allele-specific methylation mapping to pinpoint key regulatory elements in the 3p21COVID-19 GWAS region, and ask whether these elements are epigenetically altered in DS. We will engineerCRISPR/Cas9-mediated deletions in the differentially methylated sequences and measure the effects onmethylation patterns and regional gene expression. Building upon the progress of genetic engineering, we willdevelop an experimentally tractable mouse model to ask whether COVID-19 infections are more severe in agenetic background that accurately mimics human DS. In both the mouse model and our human biosamplesfrom DS and controls, we will quantitate the age-dependence of methylation of COVID-19 host responsegenes. These fundamental studies, to be carried out in one year, will lay a crucial groundwork for subsequentwork using biosamples from DS individuals who have been exposed to SARS-CoV-2, cohorts that are beingorganized by our colleagues under separate funding.",2020,2022,Hackensack University Medical Center,696828,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease models | Prognostic factors for disease severity",2017 +C06996,3R01AG027060-11S1,"COVID-19 Administrative Supplement for FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III","Abstract: The SARS-CoV-2 virus that causes COVID-19 infection is among the most serious public health challenges inthe last century. However, the true prevalence of COVID-19 infection in the Hawaii community is unknown-- wedo not know how widespread undiagnosed infections are, true morbidity levels, true case-fatality rates, norwhether herd immunity exists in some populations. This information may help facilitate easing of socialdistancing measures among other important epidemiological issues. Data from Johns Hopkins Universitysuggest that Hawaii has one of the lowest COVID-19 infection rates in the United States (U.S.) with only 36confirmed coronavirus cases per 100,000 persons (as of mid-April 2020). This was much lower than the U.S.national rate of 177 infections per 100,000 persons - both of which are hypothesized to be vastlyunderestimated, primarily due to high numbers of undiagnosed infections. One approach to help resolve thesechallenges is to test populations for COVID-19 antibodies (Ab). Early results from such studies in the U.S.mainland, Germany, and Holland, have found that 2% to 30% of populations have previously been infectedwith this coronavirus.We propose to help address these issues by sampling an underrepresented population of older Asian-Americans in Hawaii that have been well studied for other outcomes of interest (e.g. health habits,comorbidities, genetics, etc.) using a reliable Ab test that has FDA emergency use authorization (EUA) and thehighest sensitivity and specificity.We propose the following Specific Aims:Primary Aim: Test the hypothesis that the prevalence rate of prior COVID-19 infection in middle-agedand elderly persons in the Japanese-American community in Hawaii will be higher than reportedprevalence rates. Since the majority of persons in Hawaii tested for COVID-19 infections thus far have beensymptomatic persons, we hypothesize that the actual prevalence rates of prior virus infection within thiscommunity are much higher than official reports from the Hawaii Department of Health (Hawaii Department ofHealth est. 36 cases per 100,000 persons in mid-April 2020). Our study sample will be drawn from a stratifiedrandom sample of over 2,000 previously recruited Kuakini Honolulu Heart Program Offspring Study (KuakiniHHP Offspring Study) participants (n=1,200; age range = 50-90 years).Exploratory Aim #1: Test the hypothesis that those with SARS-CoV-2 Ab+ (positive) tests, and whopossess the longevity-associated FOXO3 and ACE-2 (anti-inflammatory) genotypes, will haveexperienced less severe COVID-19 related-illness (e.g. fewer overall symptoms, fewerpulmonary/cardiovascular symptoms, fewer hospitalizations, shorter duration of illness, etc.) thanthose with the common genotype. These study participants will be drawn from the Kuakini HHP OffspringStudy cohort who test Ab positive (est. at 2%-30% of sample, i.e. 32-480 persons). Ab+ participants will beasked to complete a questionnaire detailing severity of symptoms and stratified by FOXO3 genotype.Exploratory Aim #2: Test the hypothesis that the longevity associated FOXO3 genotype and protectiveACE-2 genotype will correlate with lower risk for COVID-19 infection i.e. fewer FOXO3/ACE-2 protectiveallele carriers will test positive for SARS-CoV-2 Ab. We hypothesize that those with the FOXO3/ACE-2longevity-associated genotypes will be protected from COVID-19 infection.",2020,2022,Kuakini Medical Center,460652,Human Populations,Asian,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2005 +C06998,3RF1AG063913-01S1,Big data and small molecules for Alzheimer's disease,"Abstract: More than half of residents in nursing home communities suffer from cognitive impairment withAlzheimer's disease (AD) or AD related dementia (ADRD), and one-third of all US COVID-19 deaths are long-term care facility residents. The COVID-19 pandemic places AD patients at a greater risk of respiratory failureand mortality. Hypertension, which is prevalent among elderly populations, results in more severe COVID-19symptoms. The goal of this supplement NIH application is to examine whether AD patients vulnerable toinfection by severe acute respiratory syndrome coronavirus (SARS-CoV-2) can improve clinical outcomes ofCOVID-19 with angiotensin converting enzyme inhibitors (ACEI). This supplement application fits within thescope of our NIA-funded parent project, ""Big data and small molecules for Alzheimer's disease (RF1-AG063913)."" The hypothesis from the parent project was that tauopathy and related neurodegenerativedisease pathologies can be suppressed in mice treated with ACEI and statins. The hypothesis for thissupplement project is that ACEI reduces the susceptibility, severity, and improves outcomes of SARS-CoV-2 infection in AD patients. This supplement research shares the same goal of the parent project, whichaims to meet an urgent need to identify and fast-track new AD therapies (ACEI) with a clear efficacy readout.The scientific premise for our approach is strong. First, angiotensin II is elevated in both COVID-19 and ADpatients, making ACE (converting angiotensin I to II) the prime target for inhibition. Second, SARS-CoV-2 bindsto its target cells through ACE homolog ACE2. Third, treating human cell organoids with recombinant ACE2reduces the viral load of SARS-CoV-2, and treating patients with ACEI up-regulates ACE2 in those withhypertension. Using a national database, we have reported significantly longer preclinical (asymptomatic)intervals before AD onset in subjects treated with ACEI and statins compared to those taking neither drug. Wehave identified ~350,000 subjects on an ACEI, with sufficient power to determine whether there is anassociation between ACEI and COVID-19 among AD patients. We propose to achieve three Specific Aims.Aim 1. To determine the susceptibility of AD to SARS-CoV-2 infection. This is a unique Aim that supplementsthe parent grant by using the original data set extended with data on COVID-19 and other variables includinggeographic regions. Aim 2. To determine the association of individual ACEI with the reduced occurrence ofCOVID-19 in medicated AD patients. We will divide all ten prescribed ACEIs into blood-brain barrier (BBB)crossing and non-crossing ACEIs and determine which group of/individual ACEIs reduce the occurrence ofCOVID-19 in AD patients. Aim 3. To determine the association of ACEI therapies with the severity of COVID-19 symptoms in AD patients. The severity of COVID-19 will be defined by self-quarantine, hospitalization,intensive care unit admission, use of mechanical ventilators, as well as mortality.",2020,2024,Boston University Medical Campus,412500,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Other | Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Prophylactic use of treatments",2019 +C06999,3P50AA005595-40S1,Epidemiology of Alcohol Problems: Alcohol-related Disparities,"The COVID-19 (C-19) pandemic has drastically changed life in the US, starting in March 2020 with stay-at-homeorders for much of the population and mass closures of businesses, including on-premise alcohol outlets. Todate, off-premise alcohol sales have been maintained in most states, and delivery and to-go options temporarilyexpanded. Alcohol sales in March 2020 were substantially higher than expected, indicating consumers increasedhome alcohol stocks, and potentially consumption. By June 2020, bars and restaurants have re-opened in manystates with varying distancing restrictions, prompting concerns of virus spread through congregation. The focusof this Center Project was originally on analyses of selected major causes of illness, injury, disability and deathwhere significant racial/ethnic and socioeconomic disparities are evident in the US and which are substantiallyalcohol-related. The proposed revision Aims will focus on changes in drinking patterns, substance use andmental health measures from before to during the C-19 restriction period, associations between drinking patternsand C-19 risk behaviors and behavioral health care need, access and utilization with attention to racial/ethnicand socioeconomic disparities. The 2019-2020 National Alcohol Survey (N14) completed fielding on April 20,2020 with 80% of cases collected before March 2020 and included web survey respondents recruited throughaddress-based sampling (ABS; n=5,176) and telephone respondents recruited through random digit dialing(RDD; n=1,323). We propose to re-survey 1,500 N14 ABS and RDD respondents with a follow-up instrument,N14C, focused on drinking, substance use, and C-19 risk behaviors and attitudes in the C-19 period. Thislongitudinal design allows us to build on the rich lifecourse data and pre-C-19 measures collected in N14,integrating new questions on recent substance use behaviors and problems, physical and mental health, and C-19-related risk behaviors, attitudes and impacts, including job loss and financial insecurity. N14C questions onalcohol and drug use and related problems will reference appropriate C-19 period timeframes, including duringstay-at-home orders (closed period) and during phased reopening (open period). Changes in alcohol and druguse, co-use and problems will be assessed through comparisons with N14 responses. N14C questions willinclude drinking motives and alcohol purchasing, as well as C-19 risk behaviors such as mask wearing, handwashing and congregating in groups of non-household members. Updated geocoding information of areacharacteristics and policies, such as bar closures and expanded delivery, will be utilized, allowing policy analysesutilizing within-person, pre-post comparisons to assess impacts on alcohol use and problems. Measures of anindividual's pre-existing health conditions, including diabetes, hypertension and heart disease, will facilitateanalyses of factors expected to raise the risk of C-19 impacts and measures of depression and anxiety symptomsand discrimination will be utilized for important and timely analyses focused on mental health, stress, anddiscrimination experiences related to C-19 impacts.",2020,2021,Public Health Institute,287615,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Impact/ effectiveness of control measures | Indirect health impacts | Other secondary impacts,1981 +C07000,1R21ES032680-01,Per- and Polyfluoroalkyl substances (PFAS) Exposures and COVID-19 in Firefighters,"PROJECT SUMMARY/Abstract: The spread of SARS-CoV-2 infection and its associated disease state, COVID-19, has led to a global pandemic.Exposure to per- or polyfluoroalkyl substances (PFAS) is associated with reduced immune response, but itseffect on COVID-19 is not known. We have a time-sensitive opportunity to determine the effect of serum PFASon COVID-19, building on a unique statewide firefighter testing program for SARS-CoV-2 antibodies. Our long-term goal is to identify health risks of PFAS mixtures. Our objective in this application is to evaluate the effectsof PFAS exposure levels in firefighters in regards to the severity of and immune response to COVID-19 infection.Our hypotheses are that increased PFAS serum concentrations will increase the severity of COVID-19 infectionand reduce post-recovery serologic titers, which could thereby increase risk of later re-infection. We will testthese hypotheses through two specific aims: 1) Determine the association of serum PFAS concentrations withinfection severity; and 2) Determine the association of serum PFAS with SARS-CoV-2 antibody titers. For aim1, recruiting from our state registry, we will enroll 100 Tucson and Phoenix firefighters with positive SARS-CoV-2 IgM and/or IgG antibodies, and collect and analyze their serum for PFAS. Using an online survey instrumentcompleted at the time of biological sample collection, we will obtain information on whether the subjects hadCOVID-19 infection(s) confirmed by diagnostic testing, extent of symptoms (if any) consistent with COVID-19infection, and whether they were hospitalized. We will evaluate the association between serum PFAS and: 1)severity of symptoms; 2) symptomatic vs. asymptomatic COVID-19 infection; and 3) hospitalization. For aim 2,we will repeat SARS-CoV-2 IgG testing after five months and ten months in all firefighters enrolled in the studyto measure changes in immune response and to test the association of PFAS levels and longitudinal changesin IgG using generalized linear regression models that account for repeated measures. At study completion, wewill have documented the effects of PFAS exposure on the likelihood of a symptomatic COVID-19 infection andsymptom severity in a highly exposed population, as well as effects of PFAS exposure on the subsequentimmune response persistence. The proposed research is significant given the potential for PFAS exposure toincrease the risk of already severe health consequences of COVID-19 and to reduce long-term immuneresponse. The proposed research is innovative as it is the first to our knowledge to determine the associationbetween serum PFAS levels and COVID-19.",2020,2022,University Of Arizona,254748,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +C07001,3R01AA028201-01S1,Chukka Auchaffi' Natana: The Weaving Healthy Families Program to Promote Wellness and Resilience and Prevent Alcohol and Other Drug Abuse and Violence,"Project Summary: Alcohol and other drug (AOD) abuse and family violence are secondary health effects of COVID-19 and riskfactors for the Native American (NA) health disparities that drive mortality rates. Given the gap in culturally-grounded programs to address these secondary effects of COVID-19-AOD abuse and violence in families-there is a critical need to test the efficacy of digitally enhanced and sustainable community-basedinterventions. The long-term goal of the parent research is to promote health and wellness, while preventingand reducing AOD abuse and violence in NA families. The supplement will extend this to address thesecondary health effects of COVID-19 promoting access, sustainability, and engagement with a digitallyassisted intervention. Using community-based participatory research methods (CBPR), the overall objectivesof the proposed parent award are to use a stepped-wedge trial design (SWTD) to test the efficacy of thecommunity-based, ""Weaving Healthy Families program (WHF)"", which will prevent, reduce, and postpone thesecondary health effects of COVID-19, namely AOD use and violence in families while promoting resilienceand wellness (including mental health) among NA adults and youth. Objective 1 of the Supplement is toexamine the secondary health effects of COVID-19, namely AOD abuse, IPV, as well as family functioning,and mental/physical health. Our working hypothesis is that the greater stress imposed by COVID-19 willworsen AOD abuse, IPV, and family conflict, but the WHF program will ameliorate these secondary healtheffects. We continue to use the parent grant's SWTD where groups (i.e. 175 MBCI families) are randomlyassigned the order in which they receive the intervention. We examine the sex differences for COVID-19, usingsex as a moderator to understand whether and how sex moderates the secondary health effects of COVID-19and the differential effect of the WHF program by sex. We also integrate the explanatory sequential mixed-methods design to evaluate socio-behavioral impacts of COVID-19 through 30-50 qualitative interviews withfemale heads of household. Objective 2 of the Supplement is to evaluate the sustainability and feasibility ofthe WHF program with the inclusion of the mHealth component through the use of SMS text messaging toenhance the reach, access, engagement, efficiency, quality, and sustainability of the adapted evidence-basedintervention. Our working hypothesis is that the inclusion of SMS text messages for survey and sessionreminders, engagement, and psychoeducation during and after the WHF program will improve the reach,access, engagement, efficiency, quality, and sustainability of the program. We use the parent grant's CFIR andthe explanatory sequential mixed-methods design to evaluate the impact of qualitative and quantitativeengagement methods enhanced with SMS text messaging. This research is well-matched to the supplementas the digitally enhanced WHF program directly addresses the secondary health effects of COVID-19, inparticular AOD abuse, violence and family conflict, as well as health and mental health.",2020,2025,Tulane University Of Louisiana,204525,Human Populations,Other,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2020 +C07002,3R21AA028432-01S1,"Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning","Abstract: Theinducesflu-liketreatmenthealth,1,919,430societalpeopleCOVID-19.diseasemeansinfectedextremelyventilators,SARS-CoV-2 . We propose to identify alterations inthe plasma metabolome of patients experiencing different levels of severity of COVID-19. Such changesshould be pivotal in allowing the prediction of the severity of the patient COVID-19 symptoms and also providemechanistic information about the disease and its progression. In addition to our expertise in metabolomics, weare able to carry out this project because we have access to samples from the Yale New Haven HospitalSystem via the IMPACT Biorepository. This repository stores human specimens related to emergingrespiratory viral infections (with a particular focus on COVID-19) in order to support research on factors relatedto viral expression, transmission, disease severity, progression, and susceptibility. The directors of thebiorepository are co-investigators in this supplement. As such, we are in unique position to perform this novelresearch because we have: (a) the infrastructure to conduct the metabolomic analyses and we have alreadydeveloped the methodologies, (b) access to COVID-19 patient plasma samples stored at the IMPACT(Implementing medical and public health actions against coronavirus in Connecticut) Biorepository (andassociated patient records), (c) assembled an extraordinary team that includes expertise in metabolomics,virology, pulmonary and infectious disease, and immunology.of this supplementcurrent pandemic caused by SARS-CoV-2 is of major concern because (i) it is highly contagious, (ii) ita spectrum of adverse health consequences (collectively known as COVID-19) that range from mildsymptoms (fever, chills, cough) to life-endangering pneumonia and SARS, and (iii) there is no effectiveor vaccine to prevent it. To date, the SARS-CoV-2 pandemic has had devastating effects on publicwith an international mortality rate of 5.8% in infected individuals. As of June 6, 2020, the U.S. hascases and a mortality rate of 5.7%. Measures taken to stem the pandemic have paralyzed normal activities and crippled national and international economies. I n the early stages of the pandemic, olderand individuals with specific underlying medical conditions were shown to be more vulnerable toMore recently, it has become apparent that younger, ostensibly healthy individuals likely carry the and may succumb/progress to the more serious manifestations of COVID-19. Currently, there is noto reliably predict the severity of COVID-19 symptoms (or the course of COVID-19) in individualsby SARS-CoV-2 . This represents a significant knowledge deficit. Having such information would behelpful in triaging patients and allowing more efficient utilization of limited health resources, e.g.,ICU beds, and medical personnel. Nor that are associated with the various stages of COVID-19o studies have investigated metabolic alterations caused by",2020,2022,Yale University,150625,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C07003,3R41MD014075-01S1,Good Bowls: Empowering Communities to Achieve Good Food Access and Health Equity,"AbstractEmerging data indicate that those with pre-existing health conditions, such as obesity, diabetes, and heartdisease, are at significantly increased risk of contracting COVID-19, as are low income and persons of color.Research also suggests that food insecurity (lack of access to affordable, nutritionally valuable food) and poordietary intake are likely contributors to health disparities in these populations. Unemployment, poverty, ethnicminority status, and rural residence are also strong predictors of poor health. The need to provide accessibleand affordable healthy food options to support improved immune system function to higher-risk populations hastherefore become increasingly urgent as the pandemic unfolds. Nutritional status is believed to play a key rolein the prevention, treatment, and management of COVID-19, with a balanced diet and certain nutrients servingto strengthen the immune system. Yet, even as the need for nutritious food options has become more urgent,the pandemic has led to enormous food industry job loss, closing of food-related businesses, loss of restaurantand institutional markets for small to mid-sized farmers, and excess produce being wasted or donated to foodbanks /pantries where the capacity to store and distribute this volume of perishable food is limited. These effectshave dramatically amplified food insecurity,1 particularly in minority and low income populations.Equiti Foods LLC is advancing Good Bowls, a production and distribution platform to increase availability ofhealthy, affordable, locally-produced, good-tasting frozen meals to low income and minority populations in smalltowns and rural communities, while also providing economic opportunities for small businesses in ruralcommunities. The meals are based on the Mediterranean diet adapted for taste preferences and seasonalavailability of food in the southeastern US (""Med-South Diet""). Equiti Foods has tested the Med-South diet inmultiple studies and found beneficial health impacts in low income populations as well as broad acceptabilityregarding taste. This Phase I administrative supplement will focus on tailoring the platform for application incurrent COVID-19 impacted regional economies and business environments. The goal is to assist in minimizingthe health, financial and social impacts of the pandemic in health disparity populations. Specific aims include: 1)work with three identified restaurants/caterers in rural economically distressed communities (including one Black-owned and one Latinx-owned) to test the Good Bowls model; 2) assess early stage nutrition impact on customersadversely affected by COVID-19 in terms of food security, diet quality and healthy food knowledge/behaviors; 3)incorporate COVID-19-related health messaging into the Good Bowls packaging tailored to local communities.If successful, this project will establish feasibility of a Good Bowls model that will: 1) empower small scale foodproducers, invigorating local economies; 2) prevent food waste resulting from COVID-disrupted food distributionchains; 3) provide at-risk populations with nutritious food to assist in prevention and management of COVID-19.",2020,2021,"Equiti Foods, Llc",162272,Human Populations,Black | Other,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2019 +C07004,3U54AI142766-03S1,Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC),"Extensive clinical research studies are urgently needed to inform patient management strategies and developpharmaceutical countermeasures to combat the 2019 novel coronavirus disease (COVID-19). Currently,COVID-19 infections and hospitalizations are surging across the state of Florida; hence, we propose toestablish the University of Florida (UF) as a subject-enrollment and sample collection center for theImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study at three Florida health sciencecenters. In this nationwide prospective observational study, peripheral blood and nasal swabs will be frequentlycollected from consented hospitalized patients with confirmed COVID-19, with endotracheal aspirates alsocollected if the patient requires intubation. After participants are discharged, blood and nasal swabs will becollected during outpatient visits held at three-month intervals over the course of one year, allowing forlongitudinal analysis of the virus's effects on the immune system both during active infection and followingrecovery. Through the OneFlorida Clinical Research Consortium (CRC), we already have establishedinfrastructure including trained staff to support participant consenting/enrollment and sample collection, as wellas on site laboratory facilities for sample processing. In Aim 1, we propose to integrate three OneFlorida CRCcollection sites (Tampa General Hospital/University of South Florida, UF Health Jacksonville Medical Center,and UF Health Shands Hospital in Gainesville) into the IMPACC study. These sites have sufficient COVID-19caseload to support enrollment of 100 participants over the course of the four-month recruitment period. In Aim2, samples will be processed immediately upon collection and shipped to six core laboratories for precisionmedicine genotyping, viral sequencing, proteomics/metabolomics, antibody measurement and isotyping, aswell as immunophenotyping by CyTOF. From these collective data, IMPACC seeks to link viral burden withimmune signatures as biomarkers of acute disease severity, mortality, the development of durable immunity,and long-term outcomes in survivors. Moreover, extensive immunophenotyping data has the potential touncover new therapeutic targets to mitigate the disease severity. Initially, COVID-19 mortality was attributed toa cytokine storm and enhanced thrombosis, supporting treatment with immunosuppressive drugs in patientswith severe disease. However, in an effort to support the power of immmuophenotyping to provide keyinformation, we provide preliminary data suggesting that immunosuppression is a primary concordant featureof the disease, potentially arguing against the routine use of immunosuppressant medications. These data alsodemonstrate our ability to perform single cell RNA sequencing (scRNAseq), scATACseq, spectral flowcytometry, and ELISpot to evaluate gene expression, chromatin accessibility, protein expression, and immunecell function, respectively. With the consortium's approval to use residual IMPACC samples, these site-specificassays could be funded through outside mechanisms and the data shared across the IMPACC consortium.",2020,2022,University Of Florida,1351492,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +C07005,3R01CA202911-05S1,7T Neurosurgical Mapping Protocol for Endoscopic Resection of Skull Base Tumors,"Project Summary: Although neurological symptoms are being observed in a high number of COVID-19 patients, a prospective studyaimed at scanning recovered COVID-19 patients with advanced multi-modal neuroimaging methods has yet tobe performed. There is much to be learned about the persisting effects of the SARS-CoV-2 virus on the centralnervous system, and high-resolution magnetic resonance imaging (MRI) is the ideal non-invasive tool to revealthese effects as well as mechanisms of infection. In this work, we will leverage the high resolution and enhancedcontrasts offered by multi-modal 7 Tesla (7T) imaging to study the structural, vascular, functional, andconnectomic changes in the brain related to the pathophysiology of COVID-19. In particular, we will reveal,in unprecedented detail, brain abnormalities resulting from the SARS-CoV-2 infection as well as shine a brighterlight on possible links to loss of respiratory drive due to viral infection through the brain stem. Imaging findingswill be correlated to clinical neurological symptoms and neuropsychological measures. Three patient subgroupswill be recruited for our prospective study: non-cancer patients with neurological symptoms who did not requirea ventilator, cancer patients with neurological symptoms who did not require a ventilator, and patients who hadsevere respiratory distress and required ventilation. A retrospective study will also be performed on clinical brainMRI scans for a group of COVID-19 patients with neurological symptoms, seen at Mount Sinai Health System,and outcomes of this analysis will aid in patient selection for the 7T study and additional analysis of persistingversus transient neurological effects. Our study falls within the scope of our R01 application on ""7TNeurosurgical Mapping Protocol for Endoscopic Resection of Skull Base Tumors"" as we are applying similarmultimodal 7T imaging techniques to reveal detailed anatomy in the brain and to characterize effects of diseasein both studies. We will simply extend the cohort to include COVID-19 recovered patients and further optimizeimaging in the brain stem which will be applicable to both studies. Our study aligns with the goals of the Noticeof Special Interest announced by the NCI for administrative supplements on COVID-19 as it addressespotential for differential responses among diverse cancer patient populations to SARS-CoV-2 infection orCOVID-19 disease in central nervous system.",2020,2021,Icahn School Of Medicine At Mount Sinai,169495,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +C07006,3U54MD012388-04S4,Southwest Health Equity Research Collaborative (1),"During the COVID-19 Pandemic, the United States Drug Enforcement Administration (DEA) temporarilyrelaxed restrictions to best serve people in treatment for substance use disorders (SUD) during socialdistancing mandates. Changes include allowing longer take home doses of methadone and buprenorphinerather than coming to the clinic every day (for methadone) or weekly (for buprenorphine), and relaxedrestrictions on telehealth prescribing and treatment. These changes directly and indirectly impact theapproximately 14,500 substance use treatment programs in the United States, but the actual implementation ofthe changes is poorly understood. The overarching goals of the proposed project, therefore, are to: (1)document impacts of relaxed restrictions for telemedicine and mHealth; and (2) assess implementation of MAT""take-homes"" for people in SUD treatment in rural, underserved, and minority communities in Arizona in thewake of COVID-19. To accomplish these goals, we propose to use Rapid Assessment, Response andEvaluation (RARE) methods to complete the following specific aims: AIM 1: Identify barriers and facilitatorsto successful implementation of telehealth and mHealth for opioid treatment in the context of COVID-19 restrictions, temporary guideline changes, and ""reopening stages""; and AIM 2: Assessimplementation of medication assisted treatment guideline changes and equity in access to ""take-homes"" for people in rural and underserved populations. RARE is a well-established mixed-methodapproach designed to gather data relevant to institutions and communities as they respond to crisis situations.RARE assessment involves triangulation of multiple methods to conduct rigorous, locally responsiveassessment and evaluation within a much shorter timeframe than conventional research. We propose to useRARE methods to collect information about online care delivery program barriers and facilitators, and toprovide local communities with information about local equity, acceptability, and feasibility of potentialtelehealth and mHealth interventions. The knowledge to be gained from the proposed project will contribute tounderstanding how DEA guideline changes during COVID-19 were implemented and experienced bystakeholders, providers, and patients in treatment for opioid dependence. The proposed study is expected toprovide in-depth information about providers' and patients' experiences of the changes and inform the debateat the national level about whether policy guideline changes should become permanent after COVID-19 riskhas lessened. There is a pressing need to document experiences of the new guidelines as policymakersdecide whether to make the guidelines permanent. In-depth investigation stands to fills key gaps inunderstanding about whether and how increased access to medication-assisted treatment and more access totreatment via telehealth and mHealth platforms can improve equity for people in rural and underserved areaswho have limited access to care for substance use disorders.",2020,2022,Northern Arizona University,293101,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Research on Capacity Strengthening","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Policy research and interventions | Systemic/environmental components of capacity strengthening",2017 +C07007,3R01CA201189-05S1,Effect of SARS-CoV-2 on clinical course and NK cells in patients receiving immunotherapy,"The pandemic caused by SARS-CoV-2 has killed 430,000 people worldwide in the span of 6 months whichoverall place cancer patients at a higher risk of severe illness and death if infected, although differences betweendistinct therapy regimens are possible (e.g. chemotherapy vs. immunotherapy vs. palliation). Cancer patientswho have recovered from COVID-19 may need to resume treatment, including immunotherapy for their diseaseeven though the repercussions of this infection on their immune systems are unknown. This project will determineif cancer patients who have recovered from COVID-19 have NK cells with different functionality than cancerpatients who were not infected, and whether these phenotypes have an impact on the overall response rate andsurvival of this population.",2020,2021,Icahn School Of Medicine At Mount Sinai,168429,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C07008,3R21MD013674-02S1,Post-Hurricane Cancer Care: Patient Needs after Hurricane Maria,"PROJECT Summary: Studies evaluating the effects of natural disasters on cancer outcomes and disparities are scarce, and to thestudy team's knowledge; none have examined the impact of exposure to multiple disasters, particularly in ethnicminority groups. Currently, the team is expanding assessments to include the impact of COVID-19 and theearthquakes' secondary hazards (social isolation, unemployment, healthcare services disruption, structuraldamage) on stress biomarkers and changes in multilevel determinants of health. The proposed supplement willcomplement the scope of the parent R21 (1R21MD013674) by: 1) expanding recruitment to include additionalcancer patients (+75) and controls (+75) who were exposed to Maria, the 2020 earthquakes, and the COVID-19pandemic; 2) identifying patients' unmet psychological and medical needs resulting from the aftermath of the2020 earthquakes and the COVID-19 pandemic, and; 3) examining the impact of Maria, the earthquakes, andthe COVID-19 pandemic on multilevel factors relevant to health outcomes. The proposed supplement projectwill shift current research paradigms in health outcomes after natural disasters by exploring the physiologicaleffects of extreme stressors on biological processes known to affect cancer progression and comorbidconditions, including inflammation and stress hormones. By expanding the parent grant's scope to include the2020 earthquakes and COVID-19 pandemic, the study team will increase the understanding of the effects ofmultiple disaster stressors.",2020,2022,Ponce Health Sciences University,212707,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2018 +C07009,3P30AG021342-18S1,COVID-19 in Older Adults: A Longitudinal Assessment (VALIANT),"PROJECT SUMMARY / ABSTRACTOlder adults with COVID-19 are much more likely than younger adults to develop severe disease and to diefrom their illness. Nevertheless, the best available data suggest that more than 90% of adults aged ≥60 willsurvive. Virtually nothing is known about the long-term effects of COVID-19 infection, but there are manyreasons to be concerned that older survivors who were ill enough to require hospitalization are at risk of asubstantial decline in their health and functional status. Normal aging involves a decline in physiologic reserve,and many older adults have other underlying vulnerabilities, including multiple chronic medical conditions andfrailty. Hospitalized patients with COVID-19 endure long periods of immobility and social isolation. Upondischarge, there is the potential for limited access to community health care providers, such as physicaltherapists. Finally, reports have suggested that COVID-19 itself has the potential to cause long-termphysiologic changes, including changes in metabolism. High quality data about these phenomena are neededto guide the development of targeted interventions for older COVID-19 survivors and to inform medicaldecision-making. Because the data available in the electronic health record (EHR) are not sufficient to assessthe long-term health outcomes that matter to older adults, such as function, cognition, and symptom burden,longitudinal data about these key outcomes need to be collected from patients or their proxies. The Yale OlderAmericans Independence Center (OAIC), with a wealth of research expertise and a world-class FieldOperations and Data Management Core, is uniquely positioned to collect such data. We propose to leveragethis expertise to accomplish Specific Aim 1, the enrollment of a prospective cohort of 500 patients aged ≥60years with COVID-19 from two large hospitals in southern Connecticut, near the center of the pandemic. Wewill perform a baseline assessment at or near the time of hospitalization and then follow-up assessments at 1,3, and 6 months after discharge, with measures of physical and cognitive health, psychosocial support, frailty,quality of life, and, at the 6-month assessment, performance-based measures of mobility, pulmonary functiontesting, and a blood draw. This work will lead to a repository of outcome data that we will supplement withEHR-based variables and make available for use by other investigators. Specific Aims 2-4 draw upon thebreadth of investigative and analytic expertise at the OAIC to illustrate projects to be undertaken withrepository data. Aim 2 is an investigation of functional outcomes among critically ill and socioeconomicallydisadvantaged groups. Aim 3 involves work to characterize metabolic dysfunction among COVID-19 survivors,while Aim 4 is an examination of symptom burden. Because this study involves the collection of longitudinaldata that would otherwise not be available, it will enable foundational research into the long-term health effectsof COVID-19 in older patients.",2020,2023,Yale University,753175,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management | Health Systems Research,Disease susceptibility | Prognostic factors for disease severity | Health information systems,2002 +C07010,3P30CA013330-48S4,Novel Biologics to Treat Lung Cancer and COVID-19 Comorbidity,"Novel Biologics to Treat Lung Cancer and COVID-19 Comorbidity: Analyses of patients with COVID-19 treated at the Montefiore Medical Center (University Hospital of the Albert Einstein College of Medicine) indicate a high mortality (28%) in cancer patients, in general, and a 55% mortality in patients with lung cancer, especially those that received lung radiation 1-12 months prior to COVID-19 diagnosis. We propose to study the role that CD8 T cell depletion plays as a determinant of this adverse outcome, as CD8 T cells have been shown to provide substantial protection from lethal severe acute respiratory syndrome due to coronavirus infection. We are exploiting a novel biologics platform to provide mechanistic insight into the impact of radiation therapy on the number and quality of protective lung-resident COVID-19 T specific cells. This platform, termed synTac (artificial immunological Synapse for T-cell Activation), selectively modulates specific disease-relevant T cell clones for targeted treatment of malignancies, autoimmune disease and infectious diseases. In this unique design, single chain peptide-MHC (sc-pMHC) constructs are covalently linked to a variety of costimulatory, coinhibitory and cytokine molecules. The sc-pMHC domain acts as an ""address"" to target specific T cell clones for delivery of a range of comodulatory domains (MODS), resulting in clonal-selective T cell modulation, thus eliminating the side effects of current immunotherapeutics, which elicit global immune modulation (i.e., stimulation or inhibition of all T cells). This technology is the foundation of Cue Biopharma (Almo, founder), a publically traded immunotherapy company focused on development and application of this platform. A synTac containing the HPV-derived E7 peptide and IL-2 cytokine elicits selective T cell expansion and tumor growth inhibition of an E7-driven tumor in pre-clinical models. The human analog of this synTac (CUE-101) is in a Phase 1 clinical trial for head/neck squamous cell carcinoma - HNSCC (NCT03978689) demonstrating favorable tolerability and drug exposure. Preclinical studies demonstrated antitumor efficacy as monotherapy and with anti-PD1 treatment. Based upon these findings, Merck, collaborating with Cue Biopharma, is launching a Phase I first-line study of CUE-101 in combination with Keytruda for HPV+ advanced HNSCC. We have adapted this platform to generate viral-targeted synTacs, possessing antigenic peptides for HIV and CMV, to deliver costimulatory signals through CD28 or 4-1BB receptors. These reagents support substantial in vivo expansion of HIV- and CMV-specific T cells (in the NGS murine system), and this platform is being expanded to utilize COVID-19 derived peptides for selective in vivo expansion of protective CD8 T cells for COVID-19 treatment and cancer/radiation comorbidities.",2020,2022,Albert Einstein College Of Medicine,167791,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies,1997 +C07011,3R24AA019431-11S1,Functional Measures of Lung Health in Chronic Ethanol Drinking for Understanding SARS-CoV-2 Infection and Treatment,"PROJECT Summary: SARS-CoV-2, the causative agent of COVID-19, is responsible for a continuing pandemic with over 2 millioninfected individuals and 115,000 deaths in the US as of June 11, 2020 with cases still rising. Similar to therespiratory diseases caused by the SARS and MERS coronaviruses, COVID-19 is characterized by fatigue,cough, fever, sputum production, dyspnea, and acute respiratory distress syndrome (ARDS). ARDS is theresult of excessive lung inflammation causing the accumulation of fluid and inflammatory cell debris andleading to decreased gas exchange and oxygen levels, and eventual multi-organ failure. The leadinghypothesis for the molecular basis of SARS-CoV-2 pathogenesis is that an aberrant induction of pro-inflammatory cytokines, chemokines and soluble mediators lead to a debilitating cytokine storm that in turnresults in severe lung tissue damage (3-6). Current studies suggest a major role for myeloid cell subsets in thedevelopment of the cytokine storm, but the precise roles of pro-inflammatory alveolar monocytes andmacrophages have not been thoroughly examined and animal or human subject studies. SARS-CoV-2disruption to daily routines and social settings have led to increased sales and consumption of alcoholicbeverages. As chronic heavy alcohol consumption compromises lung health and immunity leading to increasedsusceptibility to both bacterial and viral pulmonary infections, and is a risk factor for ARDS. Thus, chronicheavy alcohol drinking could increase the chances of COVID-19 infection and exacerbate the disease course.However, there are no longitudinal studies in controlled populations that provide both precise measures of lungfunction with exact measures of alcohol consumption in human subjects. In this proposal we will obtain apulmonary functional test (PFT), a clinical diagnostic of lung infection (CT) and alveolar macrophages to theR24 AA01943 Monkey Alcohol Tissue Research Resource (MATRR). This added capacity will be a resourcefor investigators to understand19the potentially complex relationships between alcohol consumption and COVID-related-outcomes and to enhance the nation's response to the current pandemic.",2020,2025,Oregon Health & Science University,58916,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2010 +C07012,3R44CA203629-03S1,Development of Population Level Serotyping Technology and Antibody Profiling for Infectious Pathogens with focus on Influenza and SARS-CoV-2,"Abstract: The goal of this proposal is to repurpose technology developed for Next-GenProteomics to develop a highly-scalable digital serotyping technology for infectiousdisease analysis, with particular application to influenza and Covid-19. The approach isbroadly applicable and should greatly improve upon cost, sensitivity, usability, andthroughput of population-level serotyping and greatly improve infectious diseasemonitoring and surveillance.",2020,2021,Encodia Inc,728518,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2016 +C07013,3U01MD010644-05S1,Addressing Emotional Wellness among COVID-19 informal first-responders: REJOICE-P,"PROJECT Summary: The COVID-19 pandemic is currently devastating many communities across America1-3. The increases ininfection, unemployment, and death are straining resources in disadvantaged communities, such as ruralAfrican American communities4. In rural African American communities, pastors are serving as informal first-responders, responding to the communities social and emotional needs associated with the COVID-19pandemic5. For example, many are experiencing increased psychological distress such as anxiety anddepressive symptoms related to the COVID-19 pandemic. Given the decreased access to formal mental healthservices46, pastors are responsible for addressing the emotional concerns7 of congregants in addition toaddressing other psychosocial needs such as the need for financial support and food.5 Pastors, a populationalready at risk for psychological distress and burn-out,8,9 are experiencing an increase in psychological stressrelated to these added demands5; thereby, increasing the likelihood that rural African American pastors willexperience emotional unwellness (i.e. emotional distress or strain that can lead to the development of mentalillness).The parent grant seeks to test the effectiveness of a culturally adapted an evidence-based intervention toaddress emotional wellness in rural African American adults of faith. The multi-level intervention is based onbehavioral activation (BA), an evidence-based psychotherapy for the treatment of depression that focuses onidentifying and scheduling personally meaningful activities to reduce depressive symptoms whilesimultaneously addressing obstacles (i.e. avoidance) to participating in identified activities. Small groups led bylay leaders undergo an 8-session faith-based behavioral activation protocol that provides individuals witheducation about: identifying depressive symptoms, identifying pleasurable activities, scheduling pleasurableactivities, and identifying and addressing avoidant behaviors that act as barriers to completing pleasurableactivities.Given the specific need of pastors serving as informal first responders, this supplement seeks to refine theexisting REJOICE intervention to provide pastors with skills to improve personal emotional wellness related toserving on the first-lines of the COVID-19 pandemic and build the capacity of pastors to adequately respond tothe emotional needs of rural African Americans. Specifically, this supplement aims to:1) Refine REJOICE foruse with rural African American pastors serving as informal first-responders during the COVID-19 pandemicand 2) Assess the feasibility and acceptability of a faith-based behavioral activation intervention (REJOICE) foruse with African American pastors serving as informal first-responders during the COVID-19 pandemic.",2020,2021,University of Arkansas for Medical Sciences,169556,Human Populations,Black,Adults (18 and older),Rural Population/Setting,Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Indirect health impacts,2016 +C07014,3R01HD053654-14S1,COVID-19 Impacts on Time Use and Well-Being,"Summary: This supplemental proposal has one objective that falls under the parent project's first aim ofDatabase Expansion, which is to add five new years of ATUS data from 2016 to 2020; todouble the number of countries included in a web-based portal entitled IPUMS-Time Use; and toincorporate newly-digitized U.S. time diary data from the 1920s and 1930s. Our objective is tosupport data collection on the well-being, quality of life, and physical and mental health of alarge and nationally representative cohort of children and adults ages 15 and older spanningJanuary through December 2021. The COVID-19 pandemic has disrupted American's dailyroutines, increased stress and worry for many, and amplified pre-existing racial, gender, andsocial class inequities in health and well-being. Evidence suggests that these consequencesmay not be short-term, especially since the course of this pandemic is unknown. Time diarydata in general and well-being data in particular are the best sources of information forunderstanding how COVID-19 affects Americans' daily lives and perceptions of health and well-being. The American Time Use Survey (ATUS) is the only large, nationally representativesource of information about how, where, and with whom the U.S. population spends their timeoutside of paid work. The proposed data collection will replicate the ATUS Well-Being Module(WBM) that was previously fielded in 2010, 2012, and 2013, and will add a new question toassess current family well-being in response to the COVID-19 pandemic. The WBM collecteddetailed information about Americans' experienced momentary well-being at three points duringthe interview day, that can be tied to specific contexts during the day - what people were doing,where they were, who they were with, and when they felt these emotions. These data willenable the scientific community to investigate adherence to and effects of containment andmitigation efforts on daily behaviors, well-being, quality of life, and health, by subgroup. This isof particular interest to NICHD because of the link to early life conditions, family processes andparenting, and the health and well-being of the next generation of Americans, taking intoaccount variability across population subgroups. Our web-based portal, IPUMS Time Use,currently archives and makes available data from historical American surveys of time use, theAmerican Time Use Surveys from 2003 to the present, as well as data from 13 other countriesacross the globe. After processing, we will incorporate the WBM data into our datadissemination system, IPUMS Time Use, which is easily and freely accessible to the researchcommunity, and promoted broadly through webinars and a video training library.",2020,2022,"Univ Of Maryland, College Park",113625,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2006 +C07015,3R21AG065776-01S1,Non-Invasive Detection and Staging of Decubitus and Diabetic Ulcers,"Project Summary: We request funds via a competitive revision to our existing NIA award (R21 AG065776) to supportresearch on COVID-19. These supplemental funds will enable us to build and validate amultimodal contrast agent that reports the presence of Mpro-a protease intricately linked to thelife cycle of the SARS-CoV-2. Existing tools to detect and monitor SARS-type viruses are basedon PCR. While quantitative, these in vitro tools are limited in their ability to map the spatiotemporaldistribution of the virus in living subjects. The missing element is a contrast agent for specificimaging of Mpro to map and measure this specific byproduct of SARS-CoV-2 infection. This workwill accomplish this and report the presence of Mpro with conventional fluorescence as well asnovel photoacoustic imaging. The fluorescence will allow for rapid and routine in vitro assayswhile the photoacoustic modality will be used for deep tissue in vivo imaging via rodent models.Aim 1 will build the probe based on a peptide sequence that is selectively cleaved by Mpro withcell penetration based on charge. The probe will be decorated with sonophores that are in adeactivated state until the peptide is cleaved. Once cleaved, these molecules produce bothfluorescence and photoacoustic signal. Aim 2 will validate this contrast agent with a less infectiousanalogue of SARS-CovV-2 (Sindbis virus). Sindbis virus can easily be handled in BSL-2 facilitiesand will allow work to commence immediately. We will validate the probe with infected cells andinfected animals. These aims are feasible because of Dr. Jokerst's prior work in optical imagingand contrast agent construction and Dr. Siqueira-Neto's work in infectious disease includingimage-based screening tools for therapies and pathogens. The innovation of this work is the firstcontrast agent to image COVID-19 infection. The significance is that, once completed, thecommunity will have a powerful chemical tool to quantify and locate SARS-Cov-2 infection toanswer key questions about this disease: What is the time course of infection and biodistribution?;How does biodistribution change by route of infection? Are there latent disease reservoirs?; Howdo protease levels change in response to therapy? Unfortunately, none of these questions canbe answered because there are no in vivo imaging methods specific for viruses much less SARS-CoV-2.",2020,2021,University Of California-San Diego,194150,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2019 +C07016,3P30CA014236-46S3,Ultra-Sensitive Combined Antigen and Serology Rapid Test for COVID-19,"The overall goal of this proposal is to develop a new point-of-care test (POCT) -the D4-POCT- for serosurveillance of COVID-19 infection. The central hypothesis that underlies the proposal is that the D4 POCT will have the sensitivity of ELISA with the ease of use of lateral flow assays, enabling highly sensitive and user-friendly detection of host Abs generated against SARS-CoV-2. The specific objective is to develop two different formats of the D4-POCT to quantify host antibodies to SARS-CoV-2 - an indirect assay and a double antigen assay- and to compare their sensitivity and specificity with SARS-CoV-2 positive and negative blood and serum samples from infected and healthy individuals respectively. In Aim 1, we will develop a multiplexed indirect D4-POCT in which host generated antibodies against the S1 and N protein antigens of SARS-CoV-2 are captured by the two viral antigens that are printed as discrete spots on a ""nonfouling""-protein- and cell-resistant - polymer brush on glass and then the captured host antibodies are subsequently labeled with an anti-human IgG/IgM secondary antibody that is also printed as soluble spots on the chip to determine isotype specific response. In Aim 2, we will develop a competing format, a multiplexed double antigen D4-POCT in which capture S1 and N antigens are inkjet printed as discrete spots on the chip and used to capture the host antibodies, followed by labeling with fluorescently labeled viral antigens that are printed as soluble spots on the chip. Unlike the indirect scheme, the double antigen D4-POCT detects total levels of SARS-COV-2 specific antibodies, which has been shown in some studies to be more sensitive than either IgG or IgM. In Aim 3, the analytical and clinical sensitivity and specificity will be compared for both POCTs. Clinical validation will be performed by testing 30 COVID-19 confirmed patient sera samples and 30 negative controls banked before the outbreak. If successful, this project will have a potentially transformative impact on COVID-19 testing and sero-surveillance. The COVID19 D4 POCT will be useful as an epidemiologic tool to estimate the disease burden more accurately, and as a research tool to correlate Ab responses with clinical outcome broadly and for cancer patients.",2020,2024,Duke University,155412,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,1997 +C07017,3R24AA026801-02S2,Alcohol and Circadian Disruption in Shift Workers Decreases their Resiliency to COVID-19,"Abstract: Coronavirus disease 2019 (COVID-19) pandemic has upended our health care system resulting inunprecedented morbidity, mortality. It is now clear that several host risk factors like age, obesity andcomorbidity impact rate of infection and severity of disease leading to hospital ICU admission and death. Riskfactors that promote exaggerated immune/inflammatory response to the virus that is the cause of the severeand fatal disease outcome must be identified. One such factor could be alcohol use disorder (AUD) because:(1) Alcohol is by far the frequently used drug in the United States, especially in those with increasedsocioeconomic (SES) adversity (another risk factor for COVID-19 death); (2) AUD is already an establishedrisk factor for poor outcomes in hospitalized adults with influenza, a similar respiratory virus to COVID-19, andAcute Respiratory Distress Syndrome (ARDS) - the primary cause of death in COVID-19 and (3) Both alcoholand shift work negatively impacts immunity and inflammatory response to pathogens. Shift work has beenassociated with worse alcohol effects and increased cardiovascular disease, diabetes, and obesity - all riskfactors for severe COVID19. Accordingly, we will study that increased alcohol consumption is an independentrisk factor to increase the incidence and severity of COVID-19 and that circadian misalignment is a key co-factor decreasing resiliency of the host immune system to infection. Establishing this association is an urgentunmet need because one key group of vulnerable populations during this pandemic is healthcare workers, whoare on the front lines for exposure and the ability of the US to protect healthcare workers is critical tosuccessful mitigation and suppression efforts to control the pandemic. We have formed a collaboration with theAmerican Nursing Association (ANA) and propose to conduct an electronic questionnaire survey of its 200,000members to determine the impact of alcohol consumption and circadian misalignment on COVID19 diseasecourse. Our survey includes a demographic form (age, BMI, race, gender, Zip code to assess SES), alcoholuse disorders identification test (AUDIT), health-related quality of life (SF-8), Munich Chronotype questionnaire(MCTQ) or MCTQ (shift), PROMIS 8 sleep and structured COVID-19 questionnaires. Aim 1: Determine ifalcohol consumption increases incidence or severity of COVID-19 in nurses and elucidate interactionwith other risk factors. We will determine if increased alcohol use and misuse are associated with poorerhealth outcomes related to COVID-19 and if socioeconomic status, age, BMI, race, or pattern of alcohol usemodify the risk and/or are an independent predictor for poor health related outcomes. In addition, we will uselatent class analysis (LCA) to examine different alcohol groups related to poor outcomes. Aim 2. Determine ifcircadian misalignment increases incidence or severity of COVID-19 and whether it modify alcoholeffects on COVID disease course. We will use the MCTQ and MCTQ (shift) Questionnaires to assesschronotype - diurnal preferences manifested in sleep/wake preferences. This study will result in new insightsinto the role of alcohol, diet and shiftwork factors on COVID-19 pathogenesis and thus in new insights forpotential prevention and treatment of severe COVID-19 illness.",2020,2024,Rush University Medical Center,157000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2019 +C07018,3R21MD012706-02S1,"Socio-Cultural Stress Profiles, Stress Responses, and Health in Mexican American Adolescents","This competitive revision application examines ways in which the COVID-19 pandemic disrupts the daily lives of Mexican-origin adolescents who are making the transition to young adulthood. This unique sample of low- income emerging adults from immigrant families are language brokers, who translate and interpret both linguistically and culturally for their English-limited parents. The COVID-19 pandemic has amplified the socio- cultural stressors and health disparities they face on a daily basis. It is critical to capture how COVID-19 related stressors may potentially alter their health trajectories, as periods of transition (e.g., from high school to young adulthood) and environmental uncertainty (e.g., COVID-19) provide opportunities to examine where in the life course individual differences become apparent and how changes in health trajectories take shape. The three waves of data on adolescents collected from early to late adolescence before the onset of the COVID-19 pandemic will be linked to two additional waves of online data collected after the onset of COVID-19. We first examine the impact of COVID-19 stress profiles on health outcomes. We then test how COVID-19 related stress profiles influence stress responses both behaviorally and physiologically to influence health outcomes. Specifically, whether adaptive responses to COVID-19 related stressors provide avenues of resilience in health outcomes, whereas the opposite may be the case for those who experience COVID-19 socio-cultural stressors in maladaptive ways. Further, we propose to test whether the associations from socio-cultural stress profiles to stress responses to health outcomes are exacerbated or mitigated through various moderators. Physiological stress responses will be assessed via cortisol. Through a four-day daily diary study, day-to-day cortisol, sleep, and substance use responses to COVID-19 related stressors will be measured. The original sample of Mexican-origin early adolescents were sampled first as middle schoolers (Wave 1) and again one year later (Wave 2). The goal of the first year of the R21 was to re-sample the same set of adolescents after their transition to high school, in order to test how early adolescent experiences of socio-cultural stressors longitudinally influence stress responses and health outcomes. By March 2020, largely before the onset of the COVID-19 pandemic in the U.S., we completed the proposed W3 data collection to reach the stated goals of Year 1 of the R21. In Year 2 of the R21, which starts in the summer of 2020, the adolescents in the study will be making the transition from high school to young adulthood. The supplement will coincide with Year 2 of the R21 grant, a critical juncture for capturing the health trajectories of emerging adults, and an opportune time to lay the foundation for determining the COVID-19 pandemic's long-term influence on their adult health. This project has the potential to uncover processes and practices that can reduce persistent health disparities in Mexican immigrant families that may result from COVID-19.",2020,2021,"University Of Texas, Austin",195626,Human Populations,Other,Adolescent (13 years to 17 years),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C07019,3R01MD010439-04S1,Assessing the Impact of the COVID-19 Outbreak on Women with Experience in the Criminal Probation System,"PROJECT SUMMARY/Abstract: In response to NOT-MD-20-019, this administrative supplement will examine the effects of the COVID-19outbreak and related local public health mandates (e.g., Shelter in Place) in a population of women heavilyaffected by health disparities. Our parent study of health literacy and health care utilization among women inthe criminal probation system (R01MD010439) maintains a cohort of 370 women, 73% of whom are AfricanAmerican and 82% of whom have one or more chronic health condition. Emerging research indicates thatthese characteristics are linked with disparities in COVID-19 risk, infection, and mortality. Our community-based study, located in Oakland (Alameda County), California, adapted to the formal Shelter-in-Place order,beginning March 17, 2020, by modifying data collection from in-person interviews to telephone-basedinterviews. Given the public health crisis and reports from participants about its immediate impacts, webegan collecting data in May 2020 to systematically assess the medical and social consequences of theoutbreak. Coupling these new data with 12 months of longitudinal data obtained prior to the COVID-19outbreak, we propose to conduct a series of rigorous analyses to address the following Specific Aims: (1) Toassess changes in health care access and utilization associated with the COVID-19 outbreak and relatedlocal public health mandates (e.g., shelter in place) (2) To examine how health literacy and socialdeterminants (e.g., housing, income) are associated with adherence to public health mandates andparticipation in COVID-19 screening. The proposed supplement furthers the objectives of NOT-MD-20-019by addressing the urgent need to understand how COVID-19 and related public health mandates arecontributing to health disparities.",2020,2021,Research Triangle Institute,176013,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2016 +C07020,3R01MD013797-02S2,"Urgent Revision to Creating Peace: community-level intervention to reduce youth violence (R01MD013797, PI: Miller)","In response to NOT-MD-20-022 (Notice of Special Interest (NOSI): Competitive and AdministrativeSupplements for Community Interventions to Reduce the Impact of COVID-19 on Health Disparity and OtherVulnerable Populations), this urgent competitive revision (PA-18-935) aims to evaluate a novel community-based multi-level intervention focused on child and youth thriving to respond to the pressing need forbehavioral supports for youth and adults in the context of COVID-19. Residents in oppressed neighborhoodswho are predominantly Black and Latinx have increased vulnerability to COVID-19 and the economic andsocial consequences of public health mitigation measures. The pandemic has disrupted social supports andincreased social isolation among youth in these communities. This community-partnered, multi-levelintervention engages supportive adults and youth to envision child/youth thriving to increase collective self-efficacy, reduce social isolation, promote emotional well-being among supportive adults and youth, and reduceyouth violence in urban, racially-segregated neighborhoods. This intervention involves community membersand youth leaders assessing child and youth thriving in their neighborhood, using a community-developedChild/Youth Thriving Matrix tool to engage in structured dialogue on neighborhood transformation, racial andgender equity, youth engagement, and organizing for social change. Findings from discussions will informyouth engagement in racial and gender justice activities in the context of this pandemic and offer a prototypefor a community-level intervention to help mitigate the consequences of a pandemic, systemic racism, andstructural inequities. This proposed study will assess feasibility of this Child/Youth Thriving Matrix tool as acommunity-based, multi-level intervention to promote neighborhood resilience and prevent youth violence. InAim 1, we will evaluate feasibility of implementing Child/Youth Thriving Matrix within two neighborhoods (i.e.,>80% retention of participants through all sessions; satisfaction scores > 4.0 (range 1-5); identification of atleast three areas of focus for enhancing child thriving). Two other matched neighborhoods will be offered anindividual mindfulness intervention as a control condition (final anticipated n = 80 participants/arm). Aim 2 willexplore appropriateness of measures to evaluate intervention effects on individual- and neighborhood-levelcollective efficacy, emotional well-being (including mental health and social isolation), and youth violence, inpreparation for a larger trial to test this community-level intervention. These research objectives build oninfrastructure of the parent study (Creating Peace: community-based youth violence prevention to addressracism and discrimination (R01MD013797, PI: Miller)). The goal of this urgent revision is to optimize acommunity-designed, community-level intervention to address structural inequities that have become all tooapparent during this pandemic with an emphasis on neighborhood strengths and building resilience.",2020,2024,University Of Pittsburgh At Pittsburgh,324997,Human Populations,Black | Other,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Approaches to public health interventions | Policy research and interventions | Social impacts | Systemic/environmental components of capacity strengthening,2019 +C07021,3U19AI144297-02S1,GENOMIC APPROACHES TO UNDERSTAND DISEASE SUSCEPTIBILITY AND PATHOGENESIS OF SARS-COV-2,"OVERALL PROJECT Summary: The novel coronavirus, SARS-CoV-2, that was first detected in China in December 2019 has now spreadglobally. The Texas Medical Center in Houston, TX, the fourth largest city in the US, and among the top 10 inracial diversity, mounted an aggressive early response to the pandemic, primarily focused on acute care. WithinBaylor College of Medicine, members of the TMC - Genomic Center for Infectious Disease (TMC-GCID) program(https://gcid.research.bcm.edu/overview) are leveraging existing infrastructure, together with an active androbust sample collection stream linked to both clinical and community testing, to characterize SARS-CoV-2virulence and susceptibility across the region. This application requests supplemental funding to the TMC-GCIDto help support SARS-CoV-2 community-wide surveillance, complete viral genome sequencing, nasopharyngealmicrobiome profiling, and targeted host genetic analyses. The primary objective of this supplement will beachieved through the collaborative efforts of a multidisciplinary, integrated team of basic and physician scientistswith a track-record of collaboration and who are already delivering on the primary goals of the TMC-GCID. Theoverall goals of our GCID supplement is to study the biology of SARS-CoV-2 infection, the host andmicrobial genetics associated with disease, and to address community needs, particularly inunderserved communities, through the following aims: i) expand an operational Emergency UseAuthorization- (EUA-) and IRB-compliant COVID-19 qPCR screening/surveillance program featuringonline enrollment and consent as well as HIPAA-compliant return of results, ii) sequence and analyzefull-length SARS-CoV-2 genomes from infected individuals collected from the TMC and surroundingarea, iii) identify microbial co-colonization/co-infections that predict COVID-19 disease severity and/oroutcome, iv) Characterize the host genetic variation with respect to viral titer, disease severity, andoutcome in patients positive for COVID-19, including polymorphisms in human leukocyte antigen (HLA),angiotensin-converting enzyme 2 (ACE2), and natural killer cell immunoglobulin-like receptor (KIR)regions. This supplement will leverage the cutting edge, high-throughput sequencing strategies andtechnologies supplied by the TMC-GCID Sequencing Technology (ST) Core, in generating discoveries, data,tools, and reagents that will be analyzed and disseminated to the infectious disease community through theTMC-GCID Data Management Analysis and Resource Dissemination (DMARD) Core. The result will be acomprehensive genetic profiling of hosts and microbes in SARS-CoV-2 infection that will reveal pathogen geneticvariants associated with individual host response phenotypes that will inform precision medicine-basedtherapeutics and diagnostics, not just for SARS-CoV-2, but for other pandemic threats that we have alreadyobserved to profoundly change the world around us.",2020,2022,Baylor College Of Medicine,100000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease susceptibility | Disease pathogenesis",2020 +C07022,3P20CA221697-04S1,The Impact of COVID-19 Pandemic on Cancer Care and Health-Related Quality of Life of Racial and Ethnic Minority Women Diagnosed with Breast Cancer,"The unprecedented burden of the COVID-19 pandemic has critical consequences for the delivery of cancer care: patients present greater vulnerability to the disease and newly implemented treatment pathways and protocols may affect long-term survival because of suboptimal or delayed care. For racial and ethnic minority women receiving treatment for breast cancer, institutional measures implemented to regulate access of patients to medical settings and modifications in therapy sequence may exacerbate the existing disproportionate burden of the disease. Therefore, understanding the impact of COVID-19 on the cancer care received by minority groups and identifying potentially modifiable factors to inform future models of care delivery is critical. The U-HAND (University of Houston/MD Anderson) Program to Reduce Cancer Disparities (P20CA221697; 9/22/17-8/31/21) is a collaborative partnership between the University of Houston and The University of Texas MD Anderson Cancer Center that supports excellence in educational programming and innovation in research that affects health equity among racial/ethnic groups disproportionately affected by cancer disparities. The proposed Administrative Supplement application is a natural extension of the aims of the UHAND partnership and it is reflective of its overarching mission to execute innovative social/behavioral science aimed at mitigating cancer inequities for Black and Hispanic groups. Specifically, the proposed Supplement will be an extension of this goal by investigating the impact that the COVID-19 pandemic has on the receipt of optimal breast cancer care among women from racial and ethnic communities disproportionately affected by the illness and its psychosocial sequelae. This proposal is a logical next step building upon the Administrative Applicant's expertise on the intermediate determinants of cancer-related outcomes. Pilot data collected will assess differential rates of cancer care disruption and health-related quality of life among Black and Hispanic women diagnosed with early-stage breast cancer (as compared with non-Hispanic white women), and examine how proximal, intermediate, and distal determinants of disparities contribute to these outcomes. It is envisioned that the study will yield information about ""at-risk"" patients and ways to leverage existing social resources. Finally, these findings will be used to inform future multilevel interventions able to sustain effective models of care delivery in a post-acute COVID-19 environment. During the one-year Administrative Supplement grant period, research and mentored training activities will help the applicant complete the research aims of the proposed project, and develop skills that will support her understanding of mechanisms that contribute to disparities in both health care utilization and outcomes among diverse groups to foster a successful career in reducing and eliminating cancer disparities.",2020,2021,University Of Houston,153000,Human Populations,Black | White | Other,Adults (18 and older),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C07023,3U01AA020780-10S1,URBAN ARCH 4/5 Russia Cohort-Targeting HIV-comorbidities with Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-infected Russians,"PROJECT SUMMARY / ABSTRACTOver 4,000,000 people worldwide are infected with COVID19 and cases are rising. Acute respiratory infections(e.g., Severe Acute Respiratory Virus), are associated with increased cardiovascular disease (CVD) risk, andearly data indicate that COVID19 is associated with higher CVD risk. People living with HIV (PLWH) also haveincreased CVD risk compared to uninfected people and this risk is highest among those who arehazardous drinkers and smokers. Our research is designed to reduce CVD risk among these high riskPLWH and to elucidate key mechanism(s). St PETER HIV (U01AA020780) is a randomized controlled trial inSt. Petersburg, Russia comparing the effects of nicotinic partial agonists on alcohol consumption, smoking,and inflammation and CVD risk among PWLH who are heavy drinkers and smokers. The Alcohol associatedComorbidity and Microbiome Evaluation (ACME ½ U01AA026222) study, nested within St PETER HIV,examines the gut microbiome as a novel pathway for increased CVD risk among these PLWH. HIV infectionand hazardous drinking both cause microbial translocation, which increases systemic inflammation and leadsto CVD. Whether COVID19 co-infection among PLWH who drink and smoke increases inflammation,alters the gut microbiome (i.e., reduces beneficial butyrate-producing bacteria which protect the gutfrom microbial translocation) and by extension alters the plasma metabolome (e.g., reduces plasmabutyrate levels) is unknown. Sparse data describe the prevalence of COVID19 among PLWH who are heavydrinkers and smokers, and no data exist assessing the association between COVID19 and biomarker levels ofinflammation and the plasma metabolome (e.g., butyrate) in this population. Our overarching hypothesis isthat COVID19 is a CVD risk factor among heavy drinking and smoking PLWH. For this application, wehypothesize that COVID19 infection will be: (1) common among St PETER HIV participants; (2) associatedwith increased inflammation (e.g., higher IL-6); and (3) associated with an unfavorable metabolomic profile(i.e., lower plasma butyrate) as compared to those not infected with COVID19. To test our hypotheses, we willleverage existing data from and collect new data among St PETER HIV and ACME 1/2 participants includingalcohol measures using the timeline follow-back; biomarkers of inflammation, data on comorbid conditions,longitudinal stored blood and fecal samples and imaging data. New data will include: COVID19 survey itemsand testing, alcohol and smoking data, and inflammatory/metabolomic biomarker testing. We will leveragethese data to complete Aim 1: to describe and estimate prevalence of COVID19 infection in the St PETER HIVcohort; Aim 2: to determine the association between COVID19 infection and biomarkers of systemicinflammations; and Aim 3 (exploratory) to determine metabolic profiles among heavy drinking and smokingPLWH. Completing these aims will advance understanding of COVID19 effects on innate immune function andthe plasma metabolome. Results will inform future interventions targeting the GI microbiome among PLWH.",2020,2021,Boston Medical Center,186966,Human Populations,Unspecified,Unspecified,Unspecified,Smokers | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2011 +C07024,3R01AG063400-02S1,A Precision high content screening assay for AB-mediated neuronal cell cycle reentry,"Project Summary: We have established a human iPS-derived neuronal-glial cell model system that we areusing to (1) study AβO-induced neuronal cell cycle reentry (CCR) as well as (2) screenfor compounds that inhibit AβO-induced neuronal CCR. We now propose to adapt thiscell-based model system to evaluate the effects on SARS-CoV-2 spike protein-ACE2binding on neuronal ""fitness"", responsiveness and intracellular signaling as well as use toscreen for small molecule inhibitors that may used for the next generation SARS-CoV-2therapeutics.",2020,2022,University Of Virginia,161500,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2019 +C07025,3R01MD012190-04S1,Examining the Role of Sleep Disturbances in Contributing to Health Risk Behaviors and Cardiometabolic Outcomes in Urban Native American Youth,"Project Summary/Abstract: The coronavirus pandemic poses unprecedented challenges for people across the lifespan, including youth,and are likely more pronounced for those who live with poverty and health inequities. American Indian/ AlaskanNatives (AI/ANs) are one of the highest risk racial/ ethnic groups for health disparities, and they are aparticularly vulnerable group for adverse health and socioeconomic impacts of the novel coronavirus pandemic(COVID-19). Only one prior study to date retrospectively assessed the long-term psychosocial impact ofquarantine on youth and families following an infectious disease outbreak (H1N1 or SARS), and none haveassessed the impact on youth in the midst of the pandemic. AI/AN adolescents experience disproportionatelyhigh rates of comorbidities known to exacerbate the negative effects of the novel coronavirus, including heartdisease, diabetes, obesity, as well as behavioral health problems, including depression and alcohol and otherdrug (AOD) use problems, which may be exacerbated during stay-at-home orders. This application is beingsubmitted in response to NOT MD-20-019 Notice of Special Interest: Competitive and AdministrativeSupplements for the Impact of COVID-19 Outbreak on Minority Health and Health Disparities. Our aims are asfollows: Aim 1a. Using two waves of data (baseline and during the coronavirus pandemic), we will examinechanges in individual (e.g., technology use), family (e.g., conflict and cohesion), community (e.g., sense ofcommunity), and cultural (e.g., engagement in cultural activities) risk and protective factors, and changes insleep, risk-taking and mental health (depression, anxiety, and post-traumatic stress disorder, PTSD). Aim 1b:Using two waves of data, we will examine how changes in risk and protective factors influence changes insleep, risk-taking behaviors, mental health. For example, we hypothesize that increases in food insecurity willbe associated with greater increases in sleep problems, risk-taking behaviors and mental health problems,whereas increases in engagement in cultural activities will be associated with better outcomes. Aim 2. Usingthe newly added COVID-19 specific questions, we will examine the association between COVID-19 relatedknowledge, risk perception, and behavioral responses, and challenges related to COVID-19 public healthmeasures (e.g., being affected by school closings) and sleep, risk-taking behaviors, and mental health. Aim 3.Randomly select a subsample (N=25) of adolescents and administer qualitative interviews to examine how thecoronavirus outbreak has affected AI/AN adolescent sleep habits, routines, and behaviors. This study willfacilitate better understanding of how to plan support services and prevention measures for this underservedgroup of adolescents. Our findings will also move the field forward as this is the only study of sleep health inthe context of the coronavirus among urban AI/AN youth.",2020,2022,Rand Corporation,187840,Human Populations,Other,Adolescent (13 years to 17 years),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2017 +C07026,3U54MD007598-12S3,Accelerating Excellence in Translational Science (AXIS) - Administrative Supplement,"SUMMARY/ABSTRACTUnderserved and under-resourced African American (AA) communities face two major COVID-19 relatedchallenges during this pandemic. One major challenge, at the community level, is the increased risk ofoutbreaks of COVID-19 at faith-based gatherings. The second major challenge is the negative impact of thispandemic on the management of chronic conditions, particularly older adults with co-morbidities andunderlying conditions. AA older adults, specifically those managing comorbidities and social isolation, are oneof the most vulnerable groups susceptible to COVID-19 infection and have the most severe and criticalconsequences of this pandemic. AA older adults with co-morbidities, who heavily rely on county-based safety-net facilities, have had to change their patterns of seeking required medical care to manage their chronicconditions, including delaying, reducing, or stopping visits to primary and specialty providers, or to a pharmacyto obtain medication and treatment. Reduced routine access to health care providers and prescribedmedications, coupled with risky health behaviors during the pandemic, may substantially exasperate existingdisparities in healthcare utilization, non-adherence to management of chronic conditions, unhealthy lifestyles,and poorer health outcomes among underserved AA older adults. This multilevel, multidisciplinary,theoretically-based, culturally sensitive, community participatory intervention addresses these challenges intwo phases. In Phase One, we collaborate with 10 AA church leaders on implementing Federal and State(California) public health guidelines for churches for reducing COVID-19 risk in predominantly AA churches inSouth Los Angeles, potentially impacting over 3,000 parishioners. In addition, we collaborate with 10 AAchurches to train 30 church-based AA young adults as health advisors to master information about COVID-19and its impact on the daily life of underserved AAs, particularly, older adults with underlying multimorbidity orsocial isolation. In Phase Two, we recruit 265 AA older parishioners to receive a telehealth-based culturallyand spiritually sensitive intervention that provides health coaching and support. The goal of this phase is tomitigate the negative impact of COVID-19 on the management of chronic health conditions, and to reducehealthcare avoidance behaviors and psychological distress caused by the pandemic. This study buildssustainability for the AA community with the training of 30 AA church-based health advisors who will be avaluable community resource as they can continue to provide coaching and support after the intervention.Through collaboration with AA church leaders in South Los Angeles, we ensure that AA ministerial leaders areat the forefront of our efforts to assist in the development of a healthy community. This intervention seeks tohelp one of the most vulnerable populations impacted by COVID-19 and is strongly endorsed by the CaliforniaBlack Health Network.",2020,2024,Charles R. Drew University of Medicine and Science,242549,Human Populations,Black,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2009 +C07027,3RF1AG059088-01S1,"Effects of apoE Isoform, Sex and Diet on Insulin Regulation in Brain","Project Summary: Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) causes a world-wide pandemicinvolving a cytokine storm. Besides direct action at the lung and heart, SARS-CoV-2 has alsobeen shown to cross the blood-brain barrier (BBB), being recovered from cerebrospinal fluid(CSF) and brain tissue. Its ability to invade the brainstem and so affect central nervous system(CNS) control of breathing may contribute to its ability to induce respiratory failure. There areseveral reasons why Alzheimer's disease (AD) patients are at a special risk for COVID-19. Ageis a significant risk factor, where the elderly are more susceptible to COVID-19 by being morelikely to progress to severe disease, showing increased mortality and different clinical featuresthan young and middle-aged patients. The combination of COVID-19 and dementia, anotherpandemic currently present in our aging society, is being considered a ""double hit"" and raisesconcerns regarding dementia care during COVID-19. SARS-CoV-2 has 3 viral envelope proteins(S, E, and M) with the S being the protein that mediates attachment to the host cell, capable offusing to the angiotensin converting enzyme 2 receptor (ACE2R). Several lines of evidence linkACE and the apolipoprotein E (apoE) isoform, E4, another risk factor for developing AD. Whileworking directly with the SARS-CoV-2 virus is valuable, it requires working in an ABSL-3 levelfacility and substantially restricts studies with non-perfused tissues. SARS-CoV-2 recombinantvirus-like particles (VLPs) offer an attractive way to study the pathogenesis of SARS-CoV-2 inanimals, without the involvement of replicating viruses. In this application, using mice expressinghuman E3 or E4 under control of the mouse apoE promoter, we will investigate the mechanismsby which apoE isoform, sex, and age can affect SARS-CoV-2 VLP transport across the BBB andimpact on cognition.",2020,2023,Seattle Inst For Biomedical/Clinical Res,376250,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity",2018 +C07028,3R15AA027655-01S1,Alcohol consumption and related comorbid conditions: health state utilities for economic evaluation in the context of the COVID-19 pandemic,"Project Summary/Abstract: The COVID-19 pandemic has created a social and health environment that is previously unknown in scopeand magnitude. Health effects include mild to severe infection with SARS-coV-2; psychological trauma fromliving through a pandemic, including anxiety and depression; emotional stress from unemployment, foodinsecurity, and caretaking; and diminished social well-being due to physical distancing and restrictions inmovement. At the same time, alcohol sales have been increasing, and many states have protected access toalcohol through declaring restaurants and liquor stores as essential businesses and authorizing off-premisealcohol deliveries, mixed drinks to-go, and curbside pickup. The interplay between alcohol consumption andthe effects of the COVID-19 pandemic are as yet unknown: consumption may be changing in response toCOVID-19 circumstances and hazardous drinking may be increasing with negative consequences on healthand well-being, or consumption changes may be limited to the low-risk end of the spectrum with little or noeffect on well-being. This study will conduct 3 successive cross-sectional surveys of a US populationrepresentative sample to assess alcohol consumption, health-related quality of life (HRQoL), and COVID-related conditions at an individual level. The resultant dataset will allow for estimates of the associationbetween alcohol consumption and HRQoL while under different conditions of COVID-19 experiences. It willallow examination of potential heterogeneity across population subgroups-varying COVID-19 conditions,varying consumption, and varying effects of the two. The study will also compare pre and during COVIDconsumption and HRQoL using prior US data from NESARC-III as a baseline, reflecting population patterns inthe 2013-14 period. As the COVID-19 pandemic is a highly dynamic situation, it is important to collect USpopulation data now to inform behavior in the early stages of response. Our results will inform alcohol policyand will enable accurate evaluation of alcohol interventions in light of the ongoing pandemic.",2020,2021,University Of North Carolina Greensboro,151382,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C07029,3RF1AG063811-01S2,"Factors associated with hospitalization, ICU use and death among vulnerable populations diagnosed with COVID-19","Project Summary. As of April 30, 2020, over 1 million individuals in the U.S. have been diagnosed withcoronavirus disease 2019 (COVID-19). Patients with COVID-19 may develop various symptoms - while themajority of patients have mild symptoms, some require hospitalization, admissions to intensive care unit (ICU),and may die. To date, there is only limited knowledge on risk factors associated with the severity of COVID-19.First, older adults have been found to have higher risks of developing severe symptoms of COVID-19 and aremore likely to be hospitalized or die. Studies have suggested that some underlying conditions, such ashypertension, diabetes, or obesity, are associated with the severity of COVID-19. However, it is unknown towhat extent these comorbidities explain the variation in the severity of COVID-19, whether older age isindependently associated with the severity of COVID-19; and whether and how older age modifies therelationship between comorbidities and the severity of COVID-19. Second, it has been reported that blackAmericans experienced a higher rate of COVID-related hospitalization and were more likely to die of COVID-19, compared to white Americans. However, it is unknown what may contribute to such racial difference -whether it is due to the differences in health conditions between blacks and whites, or due to thecharacteristics of the community where they reside in, or due to some other factors that are also associatedwith race. The objective of this study is to identify individual risk factors that are associated with the severity ofCOVID-19 (i.e. hospitalizations, ICU use and death), especially among older adults, and to understand reasonsthat may contribute to racial differences in COVID-19 severity. To achieve these goals, we will use the daily-updated national Veterans Affairs (VA) data, which contain rich individual-level information on veteransdiagnosed with COVID-19. As of April 30, 2020, almost 9,000 veterans have been diagnosed with COVID-19,and about 500 had died, thus providing a large study cohort. This proposed study has two Specific Aims:1) Toidentify individual risk factors that are associated with COVID-19 related hospitalizations, ICU use andmortality, to understand the role of older age in COVID-19 severity, and to build a predictive model for COVID-19 severity by machine learning; and 2) To examine reasons for racial differences in illness severity amongveterans diagnosed with COVID-19: whether and how such difference is related to individual factors andcommunity characteristics, especially socio-economic status. This study is innovative because it will be the firststudy to examine the role of multiple risk factors in the severity of COVID-19 by using national data withdetailed individual-level information and machine learning algorithm; and it will be the first to examine thereasons, including the role of social determinants, for racial differences in COVID-19 severity. This proposedresearch is significant as it will help to identify patients with the highest-risk phenotypes, thus providing insightsinto disease prevention and resource allocation.",2020,2024,University Of Rochester,578879,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2019 +C07030,3R01EY029033-03S1,Leveraging Maps and Computer Vision to Support Indoor Navigation for Blind Travelers,"Leveraging Maps and Computer Vision to Support IndoorNavigation for Blind TravelersAbstract: COVID-19 has made traveling as a blind or visually impaired person much riskier and moredifficult than before the pandemic. As a result, people with visual impairments may limit theiressential travel such as trips to the doctor's office, the pharmacy and grocery shopping andwalks for exercise or leisure. Accordingly, the goal of this COVID Supplement, which builds onand expands the work being conducted by the parent grant, is to develop a COVID map toolthat provides fully accessible, non-visual access to maps. This tool will allow visually impairedpersons to explore maps and preview routes from the comfort of their home, allowing them toplan their travel along safer, less congested routes using crowdedness data. In addition, the toolwill present county-by-county COVID incidence data in a fully accessible form, which will informtheir travel plans over greater distances. Thus, this project will give visually impaired personsthe tools and confidence to undertake safer, more independent travel.",2020,2022,Smith-Kettlewell Eye Research Institute,406525,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2018 +C07031,3UL1TR001445-05S2,Clinical and Translational Science Award (NYU),"Project Summary: COMBATCOVIDThe coronavirus (COVID-19) pandemic has affected every corner of the globe and has redefined healthcarethroughout the United States. COVID-19 cases in the New York City tri-state area have reached anextraordinarily high number and have quickly become the epicenter region of the crisis in the United States. InNew York State alone, there are over 372,000 confirmed cases as of June 1, 2020. NYU Langone Health(NYULH) has been particularly hard hit, with more than 8,100 COVID-19 hospitalizations to date.In response, the entire clinical research community is marshalling resources in an attempt to improve ourunderstanding of how the virus spreads, how it infects various tissues in the body, which patients are moresusceptible to infection and fatal outcomes, which therapeutics improve symptoms and survival, whether theimmune response confers long-lasting protection against reinfection, and many other crucially importantquestions.The complexity of the development of this disease and unpredictability of progression into severity, as well asthe variety of phenotypic outcomes observed during and post COVID-19, pose major challenges inunderstanding, predicting, preventing, managing and treating this disease and its sequelae. Answers to thesechallenges can only be achieved through the comprehensive analysis of a significantly high number of COVIDcases. Given how recent and unknown this disease is, and its inherent epidemic nature, there is a limited numberof cases at individual medical institutions. The limitation of number of cases per institution becomes even morerelevant when isolating subpopulations with specific health conditions and across the lifespan.This proposed study will aim to overcome the above-mentioned challenges by supporting the formation of aconsortium comprising multiple medical institutions in the U.S.: COMBATCOVID (Consortium for MultisiteBiomedical Analytics and Trials on COVID-19).COMBATCOVID will bring together electronic health records (EHR) data from multiple participating institutionsinto a shared centralized database. As part of the COMBATCOVID effort, biorepository data of COVID-19patients collected by some of the participating institutions will also be shared and linked to the respective EHRdata. The COMBATCOVID consortium will be responsible for transferring EHR data pertaining to participatinginstitutions interested in contributing EHR data to the N3C database.",2020,2021,New York University School Of Medicine,768511,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening,2015 +C07032,3R01HD036916-17S1,Fragile Families and the Transition to Adulthood,"PROJECT Summary: The Fragile Families and Child Wellbeing Birth Cohort Study (FFCWS) is following a stratified,multistate probability sample of approximately 4,900 children born in large US cities (populationsof 200,000 or more) between 1998 and 2000. Interviews were conducted with mothers and fathersat birth and again when children were 1, 3, 5, 9, and 15 years old. Children wereassessed/interviewed at ages 3, 5, 9, and 15. The parent grant for this AdministrativeSupplement facilitates another round of FFCWS interviews focused on outcomes for thefocal children as young adults, at age 22.The parent grant includes interviews with the FFCWS young adults and complementary interviewswith the person who was the young adult's primary caregiver (PCG) at the time of the Year 15interview, providing contextual and triangulated information about the young adults' experiences.The specific aims of the parent grant are to: (1) collect new data on the health and wellbeingof FFCWS young adults; (2) collect new data on the social, economic, and physicalenvironments of FFCWS young adults; and, (3) collect saliva samples from FFCWS youngadults to be used to measure DNA methylation and telomere length.Due to the widespread impacts of the COVID-19 pandemic, additional funding for supplementarydata collection is necessary to address the parent grant's specific aims 1 and 2. The pandemicand related social and economic conditions directly affect the central domains about which theparent grant collects new data, specifically the health, wellbeing, and social, economic, andphysical environments of FFCWS young adults. Because these young adults aredisproportionately Black (49%) and Latinx (25%), and part of immigrant (13%) and low-income(59% below 200% federal poverty line (FPL)) families, they may be particularly vulnerable to theeffects of the COVID-19 pandemic. In this Administrative Supplement, we are requesting$200,000 in additional funds to cover the cost of expanding the parent grant surveys tocollect new data specific to FFCWS young adults' health, wellbeing, and environments inthe context of the pandemic.",2020,2024,Princeton University,119707,Human Populations,Black | Other,Adolescent (13 years to 17 years),Unspecified,Minority communities unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,1999 +C07033,3R01DA038154-05S3,Cognitive Control in Children of SUD Parents: A Longitudinal Multimodal MRI Study (2),"In the context of the COVID-19 pandemic, both economic and racial/ethnic disparities have been dramaticallyon display, with life and death consequences. COVID-19 serves as a deadly wake-up call regarding the needto better understand how existing social, economic and health disparities are compounded in their consequenceson disadvantaged communities in the wake of disaster, in this case, a deadly pandemic. If we are to developimproved preparations for responding to future epidemics, it is especially important to understand how COVID-19 is affecting substance use (SU) and mental health (MH) across different racial/ethnic communities. Therefore,this Stress and COVID-19 (S&C) Study is designed to address such questions by expanding an ongoing study,which immediately entered the field and is recruiting a random selection of participants from four ongoing,longitudinal epidemiologic studies examining the impact of different types of trauma and stress in the York Citymetropolitan area, epicenter of COVID-19. Taken together, these studies encompass a broad range of SES andracial/ethnic diversity (49% minority; 51% white), with the participants thoroughly characterized in multiple wavesof data during key stressors, traumas, as well as thorough diagnostic assessments of SU and MH. The first waveof the proposed S&C Study, which was initiated in mid-March 2020 to capture early indicators, is interviewing,via telephone, a random selection (n=1,000) of participants drawn from four ongoing studies (N=6,178) includingthe Parent Grant study which is focused on a (98%) minority population, and assessing the multifaceted impactsthat COVID is CURRENTLY having, especially on SU and MH behaviors, expecting a sample of N=800.This Supplement is requested to support the follow-up phase, which will consist of two additional waves of datacollection, at six and nine months after the conclusion of the first wave (months 1-3) and analysis of all waves ofdata. This Supplement will allow for a longitudinal trajectory analysis of the COVID-19 impact on SU and MHoutcomes. Importantly, this S&C Study design also allows for the utilization of 2-4 waves of detailed pre-COVID-19 data on each subject, including SU and MH behaviors and diagnoses, and a wide range of important riskfactors for post-COVID outcomes. Thus, this Supplement will support the investigation of which factors predictCOVID-driven trajectories of SU and MH outcomes, as well as other COVID-driven life changes. The cohortsbeing combined for this study were originally chosen for their unique exposures to different forms of childhoodtrauma: including disaster (9/11), parental involvement with the criminal justice system and parental SUD., Thus,this proposed study will help us determine how prior trauma impacts subsequent COVID-19 behaviors, especiallySU and MH across different exposures and across disparate racial/ethnic and socioeconomic groups. Takentogether, the design features of this proposed study represent a unique opportunity to examine how pre-existingand current disparities are contributing to COVID-19 outcome disparities in SU and MH burden.",2020,2021,Columbia University,159098,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C07034,3R01DK115545-03S1,Communication and Coping: Addressing Mothers' Needs to Improve Outcomes in Adolescents with T1D,"Summary: The impact of the 2019 Novel Coronavirus (SARS-CoV-2), COVID-19, and efforts to contain and mitigate theeffects of the virus on health and psychosocial outcomes is unknown. It is likely to be more severe inpopulations already at risk for adverse behavioral health outcomes, increasing problems among alreadydistressed families managing type 1 diabetes (T1D). Our ongoing randomized clinical trial (R01DK11545,Communication and Coping: Addressing Mothers' Needs to Improve Outcomes in Adolescents with Type 1Diabetes) offers a unique opportunity to study the effects of the unprecedented COVID-19 pandemic and socialdistancing. We propose to build on the existing project by leveraging our current sample to collect moredetailed information about the impact of COVID-19 and social distancing requirements on adolescents'diabetes management and maternal stress and coping. We will achieve these aims by adding survey itemsto assess the impact of COVID-19 and conducting qualitative interviews with mother-adolescent dyads who areexperiencing low, moderate, and high impact of COVID. By following 40 dyads over time, we will learn hownew routines and health behaviors are sustained or discontinued when social distancing requirements arereduced. In addition, we will assess how mothers' experiences of COVID-19 affect their coping, social support,and distress. The study will be conducted by a multidisciplinary team, consisting of Sarah Jaser, PhD, apediatric psychologist, and two collaborators: Lindsay Mayberry, PhD, a family and community psychologistwho uses mixed methods to study family support in diabetes, and Laurie Novak, PhD, a medical healthanthropologist with expertise in assessing the systems used in managing chronic health conditions and howthey are maintained or disrupted by disasters. The proposed study has the potential to inform ourunderstanding of how COVID-19 and social distancing influences maternal distress and family diabetesmanagement, which has important clinical and research implications. Results from this study may be used topromote the most adaptive coping and parenting strategies during times of uncertainty.",2020,2023,Vanderbilt University Medical Center,83513,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C07035,3R01DK115728-03S1,Structure-based Bioengineering of Wnt Surrogates for Intestinal Stem Cell Biology and Therapy,"Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)has threatened global health. The severity of disease and rising number of deaths from SARS-CoV-2have raised an urgent need for effective therapies. Besides respiratory symptoms, 20-50% of patientsexhibit gastrointestinal symptoms such as diarrhea and emesis. In addition, clinical evidence showsthat viral RNA can be found in rectal swabs, indicating that the intestine may be a critical target ofSARS-CoV-2 infection. In this proposal, we engineer novel high-affinity blocking agents for known entryreceptors of SARS-CoV-2 to prevent infection of human intestinal cells and pursue a longer-term goalof structure-based discovery of novel receptor targets. Aim 1 designs blocking agents that target the known interaction of SARS-CoV-2 S protein withits primary entry receptor ACE2 (angiotensin-converting enzyme 2), as well as with a novel co-receptor,CD147 (accessory protein for monocarboxylate transporters), both of which are expressed in humansmall intestinal and colon epithelial cells. In Aim 1 we will engineer an ACE2/CD147 bi-specific agentthat can simultaneously target both SARS-CoV-2 S protein receptors to improve the efficiency andspecificity of viral blockade. We utilize in vitro protein evolution by yeast cell surface display to generatehigh-affinity ACE2 and CD147 ECDs with improved affinity for SARS-CoV-2 S protein versus the wild-type ECDs These will be combined into a single bispecific agent containing both ACE2 and CD147affinity-matured ECDs and assayed in human intestinal organoids. In particular, we deploy intestinalorganoids with a ""flipped polarity"" where the apical ACE2-expressing aspect faces outwards towardsthe surrounding ECM/media instead of towards the interior lumen to better model physiologic viralinfection. In Aim 2, we will screen a CRISPRa activating library for additional human SARS-CoV-2secretome targets. The SARS-CoV-2 secretome, i.e. virus-encoded secreted or surface-exposedtransmembrane proteins, also facilitates infection of host cells and provides novel targets for SARS-CoV-2 therapeutics. This proposal leverages expertise of Chris Garcia (Multi-PI of the parental R01)in protein engineering, immunotherapeutics, and structural biology with Calvin Kuo (Multi-PI of theparental R01) expertise in organoid generation and disease modelling to design targeted therapeuticsfor SARS-CoV-2. We also utilize collaboration from the Manuel Amieva and Catherine Blish groups inorganoid apical-basal polarity inversion and BSL3 SARS-CoV-2 infection, respectively.",2020,2023,Stanford University,553964,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2018 +C07036,3P50CA098258-15S2,Evaluation of siRNA nanoformulations and aerosol delivery for treatment of SARS-CoV-2,"The 2019 novel coronavirus, SARS-CoV-2 causes COVID-19, a pandemic viral disease. This disease has resulted in world-wide fatalities, particularly in patients with cardiovascular disease, and arterial hypertension. As of June 2020, close to 6.6 million cases and death of 393,000 were reported worldwide; 1.95 million cases and more than 111,000 deaths in the US. COVID-19 poses a specific and substantial immediate burden on cancer patients who are already facing the tribulations of cancer treatment and survivorship. SARS-CoV-2 will continue to be a major threat to the lives of the above high risk groups including current and future cancer patients irrespective of the type and stage of cancer, unless a treatment that does not interfere with current cancer chemotherapies is developed urgently. CoVs are enveloped with a positive sense, single-strand RNA genome; and belong to the Coronaviridae family. CoVs are composed of at least 5 major fundamental proteins: replicase encoding polypeptide (pp1ab), Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. The viral life cycle begins with the infection, entry of the virion into cells by the binding to the host cell receptor and endocytosis (S protein), release of the viral genome into the cytoplasm and its transport to the host nucleus (N protein) where it replicates (pp1ab) and new virus particles are released. This results in respiratory, enteric, hepatic, and neurologic diseases. pp1ab, E and N proteins, unique to SARS-CoV-2 and not natively expressed in mammalian cells, offer potential opportunities for therapeutic targeting to cure COVID-19. Current drug and treatment strategies include blocking of RNA-polymerase, mRNA-based vaccines to induce antibody production, antibody treatments, and isolation of plasma and antibodies from the survivors of Covid-19. Since there are several unwarranted side effects of targeting the proteins essential to SARS-CoV-2 infection and spread, limited benefits of the current drugs, and limited availability of COVID-19 disease animal models, our strategy is to use and prioritize siRNA candidates based on the greatest inhibition of SARS-CoV-2 proteins (in model cell lines transfected with individual SARS-CoV-2 proteins) for further evaluation. We aim to use the siRNA-based therapeutic candidates with either an aerosolized (through a collision nebulizer) neutral phospholipid 1,2- dioleoyl-sn-glycero-3-phosphatidylcholine nanoliposomes (DOPC) or plant-derived vesicles (PDV) to specifically target the vital proteins of SARS-CoV-2 to inhibit its replication and virus assembly. We expect this approach will have a potent anti-viral RNAi response leading to viral clearance.",2020,2021,The University of Texas MD Anderson Cancer Center,162000,Other,Not applicable,Not Applicable,Not applicable,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2003 +C07037,3R21MD012352-02S1,CRISOL: Building Community Resilience and Integrating Efforts to Understand and Address Syndemic Health Conditions Afflicting Young LatinoImmigrants,"This goal of this competitive revision is to expand our original project to adapt, implement and evaluate a multi-level intervention to mitigate the multi-dimensional toll of COVID19 among Latino immigrant communities inPhiladelphia. Evidence of effective strategies to curb the pandemic, reduce disparities and mitigate its impactis lacking and very urgent. In the US, Latino immigrants are one of the groups hardest hit by this pandemic,with recent steep increases in COVID-19 deaths among this group corroborating their continued increased riskof infection and increased susceptibility. Latino immigrants have long exhibited disparities in diabetes, obesityand hypertension, factors known to increase COVID-19 related severity, and also in Substance Abuse,Violence exposure, HIV/AIDS, and MEntal health (SAVAME) syndemic. These syndemic conditions have beenworsened in the context of COVID-19. Latino immigrants represent a hard-to-reach and marginalizedpopulation, with extremely limited access to adequate health care and safety nets. This group faces manystructural barriers, and social vulnerabilities, that hinder their capacity to access COVID-19 testing andtreatment services and to adhere to public health interventions and measures to decrease the spread ofCOVID-19. Latinos often rely on a thin and fragmented network of health and social services organizations.Intervention to mitigate the impact of COVID-19 on this population will need to have a broad stakeholderengagement and address a wide range of health determinants. Peer-driven interventions have been effectivefor the prevention and control of infectious diseases such as HIV, STIs among Latino populations.Strengthening the links between community members and these organizations and promoting inter-organizational coordination to meet syndemic health, behavioral, economic, and legal needs of Latinocommunities are essential elements to mitigate the impact of COVID-19 on this low-resource population. Indirect response to the NOT-MD-20-022/PAR PA-18-935, our ongoing community-academic partnershipproposes to evaluate ""CRISOL Contigo,"" a multi-level intervention to address the needs created or magnifiedby the COVID-19 pandemic among Latino communities in Philadelphia. CRISOL Contigo includes a peer-driven program and mobilization of Latino-serving organizations. In aim 1, we will adapt an ongoing PopularOpinion Leader (POL) program to address the unique health, social, and economic needs related to COVID-19and the SAVAME syndemic. In aim 2, we will assess the efficacy of CRISOL Contigo to improve COVID-19related preventive health behaviors and use and access to COVID-19 related testing and care (co-primaryoutcomes). In aim 3, we will examine the impact of CRISOL Contigo on community assets, interagencycollaborations and coordination among the Latino-serving organizations in Philadelphia. There are almost 20million Latino immigrants in the US, and they play a central role in sustaining the vital parts of the US economyTailored, multi-level interventions that consider the unique needs of Latinos are urgently needed to mitigate theimpact of this and future outbreaks of COVID-19 on this disadvantaged population.",2020,2021,Drexel University,364111,Human Populations,Other,Adolescent (13 years to 17 years),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Community engagement | Social impacts | Health service delivery | Systemic/environmental components of capacity strengthening,2019 +C07038,3U24AA020801-10S1,1/3 Alcohol Research Consortium in HIV - Administrative Core (ARCH-AC),"This supplemental funding application for the Alcohol Research Consortium on HIV (ARCH)seeks to add COVID-19 related aims to our existing alcohol and HIV epidemiologic andintervention research. This proposal capitalizes on the strengths of the CFAR Network ofIntegrated Clinical Systems (CNICS), which include systematic, on-going collection of patientreported outcomes (PROs) at regular intervals as well as inpatient and outpatient electronicmedical record (EMR) Abstract: Ion. First, using data from all active CNICS patients (N >13,000), we will examine associations between alcohol use prior to and during the SARS-CoV-2pandemic with rates of SARS-CoV-2 infection, and COVID-19-related hospitalizations,hospitalization duration, ICU admissions, and mortality. Second, in a subset of hazardousdrinkers (N=100/site across 6 sites), we will implement a COVID-19 alcohol survey to capturelongitudinal data (4 surveys over 12 - 18 months) on quantity/frequency of alcohol consumption,drinking locations and partners, as well as motivations for drinking. The survey also will assessperceived personal and family threat from SARS-CoV-2, compliance with social distancing andstay-at-home orders, COVID-19 specific stressors (e.g., reduced wages, reduced/no childcare,food shortage, transportation, access to health care for ongoing health problems), and levels ofperceived stress. We will examine changes in alcohol use characteristics during and after theSARS-CoV-2 pandemic as a function of pre-pandemic alcohol use patterns, depressive andanxiety symptom severity, perceived stress and compliance with social distancing and stay-at-home orders. Third, we will study the impact of changes in alcohol use patterns on HIVtreatment outcomes. We will validate drinking self-report using the alcohol biomarker PEth in asubsample of survey participants (N=40/site across 6 sites). Finally, survey participants will ratetheir interest in telehealth alcohol counseling and provide information on availability ofequipment and internet access for implementation. Findings on COVID-19 related changes indrinking characteristics and patient interest in telehealth care models will position us toeffectively implement remote counseling models for alcohol interventions in the future.",2020,2021,Johns Hopkins University,112395,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity,2011 +C07039,3R01AA027456-02S1,Transcriptional and non-transcriptional functions of IRF3 in ALD,"Abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious and fast-spreading infectious disease, which reached pandemic status in only fourmonths and is spreading worldwide with millions of people being affected. The clinical spectrum of COVID-19ranges from mild to critically ill diseases. COVID-19 can progress rapidly into acute respiratory distress syndrome(ARDS), multiorgan failure, and even death. In the midst of the COVID-19 epidemic, there is some evidence forincreased alcohol purchases. Since people generally buy more alcohol during epidemics, increased alcoholconsumption may result in reduced resistance to infections like COVID-19 and promote the progression of thedisease. SARS-COV-2 is a positive-sense single stranded RNA (ssRNA). While alcohol consumption has notyet been shown to directly increase risk for SARS-COV-2 transmission or COVID-19 severity, alcohol negativelyaffects the both the innate and adaptive immune systems and increases risk for many infectious diseases.Importantly, recent data from both murine models of ethanol exposure and peripheral blood mononuclear cells(PBMCs) from patients with alcohol-associated hepatitis (AH) indicate that signaling by viral ss/dsRNA isdisrupted by alcohol, analogous to impact of alcohol on signaling via bacterial products, such as LPS. The parentRO-1 (Transcriptional and non-transcriptional roles of IRF3 in ALD) for this URGENT COMPETITIVE RENEWAL,we are investigating the impact of chronic ethanol on ss/ds RNA sensing and activation of IRF3-mediated cellularresponses. Here we propose to extend the scope of this RO1 to address two important aspects of the interactionof alcohol and COVID-19 in people consuming alcohol. In Specific Aim 1, making use of data from the UKBiobank, we will ask whether alcohol consumption or alcohol-related diseases increase risk of infection,hospitalization and mortality. In Specific Aim 2, we will use single cell RNA seq analysis to interrogate the impactof alcohol consumption on anti-viral responses in peripheral innate and adaptive immune cells. Understandingthe impact of alcohol use on risk for COVID-19 and characterizing the specific cellular changes in anti-viralresponses will meet an important unmet clinical need for guiding public health and medical responses to theCOVID-19 pandemic.",2020,2022,Cleveland Clinic Lerner Com-Cwru,160944,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2019 +C07040,3U01AA020784-10S1,"URBAN ARCH (5/5) Boston Cohort - Alcohol and HIV-associated comorbidity and complications: Frailty, Functional impairment, Falls, and Fractures (the 4F study)","This proposal is an urgent competitive revision designed to supplement an existing NIH-funded study to assessthe impact of the COVID-19 pandemic on alcohol and other drug use, and medication adherence that is criticalfor preventing HIV disease progression, among people living with HIV (PLWH). The COVID-19 pandemic hasprofoundly affected lives around the world. In addition to the effects of infection itself, to which PLWH may bemore susceptible, COVID-19 has affected employment, access to healthcare, and very likely, the incidenceand consequences of other health conditions, by limiting access to healthcare, and through the implementationof physical (social) distancing. PLWH may be at higher risk of consequences of social isolation, and those withaddiction, unemployment and homelessness are at an even higher risk with restrictions that affect foodavailability, hygiene (e.g. handwashing), shelter, and other traditional supports now absent from the alreadyfragile societal safety net. The over-arching goal of this proposal is to assess the impact of the COVID-19 pandemic and the effects ofphysical (social) distancing and other mitigation strategies (collectively termed ""pandemic exposure"") onsubstance use (heavy alcohol use and/or other drug use including nonmedical prescription medication use)and HIV medication adherence among PLWH. Among an ongoing, well-characterized cohort of people living with HIV/AIDS (the existing Boston ARCHCohort parent study), this project will:Aim 1: Determine prospective associations between pandemic exposure and changes in alcohol (and otherdrug) use (primarily) and HIV antiretroviral (ARV) medication nonadherence (secondarily).Aim 2: Identify associations between pandemic exposure and secondary stressors, specifically, foodinsecurity, loneliness, and pain interference (with activities); and associations between those stressors andchanges in alcohol (and other drug) use and HIV ARV medication nonadherence.Aim 3: Determine who is most affected by the pandemic by examining moderators of the associations betweenpandemic exposure and changes in substance use and HIV ARV nonadherence. To achieve these aims, a supplemental COVID-19 specific assessment will be administered to participantsat two time points (6 months apart). Baseline data on substance use, depression, and frailty, collected duringpre-pandemic assessments as part of the parent study will be compared against data collected viasupplemental COVID-specific assessments. Achieving this proposal's aims is an important step to identifyingmodifiable targets for interventions to prevent increased substance use and HIV disease progression after anextreme event such as COVID-19.",2020,2021,Boston University Medical Campus,163640,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts | Social impacts,2011 +C07041,3R37CA244775-01S1,Local microbiota signatures of pro-tumor immunity and checkpoint inhibition susceptibility in lung cancer,"The New York City area has become the hot spot of the COVID-19 pandemic in the United States with an estimated prevalence of >20%, based on preliminary serological tests. The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increased among cancer patients, and their prognosis is worse. Patients with SARS-CoV-2 are more likely to have increased proinflammatory cytokines such as IFN-, IP-10, MCP-1, IL-1, IL-4 and IL-6, many of which have been associated with the pathogenesis of lung cancer and the development of immune checkpoint inhibitor (ICI) -related adverse events. However, the effects of prior SARS-CoV-2 infection on cancer pathogenesis and response to immunotherapy are not know. Under our parent R37 grant, we investigate the role of lower airway dysbiosis on the host immune tone, lung cancer pathogenesis, and the response to immunotherapy. Using and expanding the cohort ensembled under the parent R37 we will evaluate whether SARS-CoV-2 infection affects the lower airway immune tone promoting pro-tumor immunity and ICI-related pneumonitis. To test this, we will test whether prior SARS-CoV-2 infection is associated with protumor inflammation among patients with newly diagnosed NSCLC (New Aim 4) and whether SARS-CoV-2 predisposes patients to ICI-related pneumonitis (New Aim 5). To accomplished these aims we will use our expertise in the characterization of the lower airway microbiome (including the viral fraction) and the host immune profile. We will also take advantage of the high rate of COVID-19 seropositivity in the New York area and the collection of samples from our established bronchoscopy and thoracic surgery cohorts. In addition, we will use a novel RNA sequence approach that allows for the concomitant characterization of the RNA virome, the bacterial microbiome and he host transcriptome in the lower airways. Therefore, this is an unprecedented opportunity to conduct the necessary exploratory investigations on the effects of SARS-CoV-2 infection on the pathophysiology of cancer under the infrastructure established by the parent R37.",2020,2024,New York University School Of Medicine,169500,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts,2020 +C07042,3R43CA243842-01S1,Development of the New Synthetic Triterpenoid CDDO-2P-Im for Chemoprevention of the ARDS of COVID-19,"PROJECT Abstract: COVID-19 infection is associated with substantial mortality in patients with clinical co-morbidities, includingsmoking, advanced age and diabetes mellitus. In these patients, COVID-19 infection leads to ahyperinflammatory state producing vascular leak, interstitial edema, hyaline membrane formation and ARDS.COVID-19 patients requiring ICU admission have high circulating levels of IL-6, GM-CSF, MCP and MIP1 (CCL2)cytokines compared to those with uncomplicated illnesses. This hyper-inflammation syndrome, (aka ""cytokinestorm"") is a prodromal feature of ARDS and multi-organ failure. Bronchoalveolar fluids (BALF) from patients withsevere COVID-19 are enriched in CCL2, one of the most potent chemokines driving the recruitment of monocytesinto the lung. Of note, cytokine storm is also associated with extensive lung damage in SARS-CoV and MERS-CoV infections, suggesting that innate hyper-inflammation is common to respiratory zoonoses. There is noeffective treatment currently available that may be deployed as an intervention to either prevent or amelioratethe cytokine storm of COVID-19. To address this need, our research team is actively engaged in the preclinicaldevelopment of an optimized lead agent (CDDO-2P-Im, or '2P-Im'), a highly potent synthetic triterpenoid that isthe most advanced among a class of small molecules recognized as effective modifiers of the host inflammatoryresponse. Our data show that 2P-Im broadly inhibits expression of cytokine networks and pathways underlyinghyper-inflammation. In particular, 2P-Im and its related derivatives are potent suppressors of macrophageactivation, suppressing the production of MIP1 (CCL2) by human macrophages at picomolar concentrations. 2P-Im is an innovative new drug, with a mechanism of action not shared by any other drug currently underinvestigation for in use in treating COVID-19. We envision 2P-Im will be provided to patients as an oral agentdeployed to prevent macrophage activation syndrome and disrupt progression to the ARDS of COVID-19disease in high-risk populations. 2P-Im also has potential for use in the outpatient setting as a chemopreventiveregimen to reduce risk in first responders, residents living in group settings, and other high-risk groups exposedto COVID-19. Preliminary data demonstrate potent cytoprotective effects in assays of efficacy against Influenzavirus A H1N1 and Influenza virus A H3N2. Through partnership between Triterpenoid Therapeutics (TTX) andthe Texas Biomedical Research Institute, we will pursue full-scale, IND-enabling efficacy studies in establishedmouse models of COVID-19. Specifically, we will define the capacity of 2P-Im to prevent the cytopathic effectsof SARS-CoV-2 in established, validated in vitro models of COVID-19 (Aim 1); and demonstrate the in vivoefficacy of 2P-Im against SARS-CoV-2 induced inflammation and capacity to promote survival in the establishedK18-hACE2 mouse model of COVID-19 (Aim 2). The proposed plan will lead to approval of an IND that will allowfor future clinical trials of 2P-Im in patients with COVID-19, which is the ultimate goal of this project.",2020,2021,Triterpenoid Therapeutics Inc,249799,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07043,3UH3AG060626-03S1,A Telehealth Advance Care Planning Intervention for COVID-19 in New York City,"The novel Coronavirus Disease 2019 (COVID-19) has highlighted the importance of advance care planning(ACP) for older patients who are most at risk of dying, and a critical need exists to optimize this process. ACPempowers patients to express their values and goals for care before they become too ill to do so. ACP alsoprepares patients, and their families, to make difficult decisions in real time when the moment arises. For olderpatients, COVID-19 may result in respiratory failure and high mortality rates. However, many older patientsmay prefer to avoid these interventions, especially if the mortality rate is high and death is experienced alone inthe hospital without family nearby. Motivated by the disproportionate risk to older patients from COVID-19 andthe higher mortality rates, primary care clinicians should engage all older patients with ACP to ensure theirpreferences are known and honored. Unfortunately, many clinicians have not been trained in ACP and patientsare unfamiliar with it. To address this gap, we have developed a Comprehensive Telehealth ACP Program for COVID-19that implements ACP routinely into medical care and responds to the present need for virtual communication.The ACP Program combines two well-tested, evidence-based, and complementary interventions: onlineclinician communication skills training and ACP patient video decision aids. The overall objective of thisapplication is to reduce the burden of COVID-19 and its consequences for an aging US population that mayprefer to forgo aggressive potentially ineffective interventions, and to die outside of the hospital setting. Toaccomplish this, we propose to conduct a Pre-Post trial using an open cohort design of a telehealth ACPProgram among older patients in the nation's COVID-19 epicenter, New York. We will train 250 primary careclinicians caring for 25,000 diverse patients over the age of 65 from the largest health care system in New York(Northwell Health). We will use Natural Language Processing to abstract our outcomes from the electronichealth records for patients. We hypothesize that a telehealth ACP Program of clinician serious illnesscommunication skills training combined with ACP videos will improve and sustain rates of ACP from the timethat the intervention is implemented compared to the time prior to the intervention. Clinician communication training and video decision support is a practical, evidence-based, andinnovative approach to uniformly provide robust ACP. Major strengths of this proposal are: the highlyexperienced team making this project feasible; the present infrastructure already embedded at NorthwellHealth, which has the largest number of COVID-19 patients in the US; and, the potential immediatedeployment of the intervention, if successful, across the country. This work holds the promise of improving thequality of care provided to millions of Americans during the COVID-19 pandemic.",2020,2023,Dana-Farber Cancer Inst,2405961,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2018 +C07044,3U01AA020797-10S1,"Effects of experimentally-induced reductions in alcohol consumption on brain cognitive, and clinical outcomes and motivation for changing drinking in older persons with HIV infection","Abstract: Persons living with HIV (PLWH) are an especially vulnerable population in the COVID-19 pandemic given theircompromised immune system and comorbidities (e.g., substance use, mental health issues). Currently, noresearch has examined how the broad impacts of COVID-19 (e.g., extended social isolation, anxiety, familyloss) are affecting alcohol use and care engagement in PLWH. Further, it is unclear whether these impactsaffect cognition or the brain. This urgent supplement will allow us to capture this window of opportunity andcollect timely data to address these gaps. Our ongoing U01 study of a cohort consisting of PLWH and personswithout HIV focusing on using a contingency management protocol to reduce alcohol consumption providesmany unique strengths to support this supplement. This supplement is within the scope of the parent grantbut extents the parent study by incorporating COVID-19-related questions/measures into the ongoing datacollection. We will collect additional data through questionnaires, electronic at-home cognitive testing viaCANTAB Connect, stress severity quantification via cortisol analysis of hair samples, and qualitativeinterviews. We will also conduct COVID-19 antibody tests (through blood samples) and MRIs that we conductas part of the parent grant procedure. The specific aims of this supplement include: 1) Determine theinfluence of specific psychosocial factors (e.g., social isolation, loneliness, anxiety, and food and housinginsecurity) on alcohol use trajectory and HIV-related health behavior and outcomes (ART adherence, andhealth care engagement) during the period of the pandemic and social distancing. We will also examine whichbaseline factors (e.g., clinical, demographic, neuroimaging, cognitive) best predict individual differences inoutcome; 2) Assess the feasibility and acceptability of (1) an at-home, electronically delivered neurocognitiveassessment on the CANTAB Connect system and (2) participant mail-in hair samples. For those willing andable to complete one or both of these measures, we will examine the relationships of the psychosocial factorsassessed in Aim 1 on cognitive performance and/or stress severity as measured by cortisol levels from hairsamples obtained from participants; 3) Obtain additional neuroimaging from participants to ensure we havedata from both before and after the coronavirus crisis, and (should there be sufficient prevalence), determinewhether participants found to have been infected with COVID-19 (with or without symptoms) have a greaterextent of white matter hypersensitivity (WMH) on FLAIR brain MRI, along with other associated structural,functional, and metabolic brain changes (fMRI, MRS); and an exploratory aim to will conduct a qualitativeinterview to explore factors that are subjectively judged to be interfering with drinking abstinence and HIVmedication adherence, and what might help in this regard. These results will provide valuable evidence on howthe COVID-19 pandemic affects alcohol use and HIV care, in addition to changes in cognition and the brain,which can potentially inform future prevention and treatment programs during future emergency situations.",2020,2021,University Of Florida,133466,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2011 +C07045,3R01HD095128-03S2,Maternal Inflammation during Pregnancy and Neurodevelopmental Disorders,"Abstract: The SARS-CoV-2 novel coronavirus (COVID-19) pandemic has led to over 6.25 million confirmed cases and~375,000 deaths worldwide, yet very little is currently known about the prevalence of COVID-19 infectionduring pregnancy nor the impact of the pandemic on pregnant women and their unborn children. The goal ofthis competing revision application is to establish a new pregnancy cohort to investigate the impact ofthe COVID-19 pandemic on child neurodevelopment. Maternal inflammation during pregnancy can resultfrom immune dysregulation due to infections or stress. The COVID-19 pandemic may therefore result inincreased maternal inflammation during pregnancy. Several lines of evidence suggest that inflammation canhave deleterious effects on fetal neurodevelopment. Our overarching hypothesis is that maternal COVID-19 infection and/or pandemic-related stress during pregnancy will increase risk of neurodevelopmentaldisorders (NDD) in children via in utero exposure to heightened maternal inflammation duringpregnancy. Neonatal blood reflects the maternal gestational immune profile, and IgG antibodies and pro-inflammatory cytokines measured in newborn bloodspots reflect past/present maternal infection. Thus, wefurther hypothesize that neonatal levels of immune markers (antibodies, cytokines, chemokines) willreflect maternal COVID-19 exposures during pregnancy and correlate with NDD risk. We propose alongitudinal pregnancy cohort study of women who were members of KPNC and pregnant during the COVID-19 pandemic in 2020. Utilizing prospectively collected information recorded in the electronic health records ofthe large and diverse cohort of ~40,000 pregnant women and their children receiving care at KaiserPermanente Northern California (KPNC), patient reported data from ~20,000 women who complete the KPNCCOVID-19 pregnancy survey, and newborn bloodspots from babies born to COVID-19 positive women(N~550), we will investigate the impact of the COVID-19 pandemic on child neurodevelopment. We willcompare NDD diagnosed in the first 24 months of life between children born to women 1) with and withoutCOVID-19 infection during pregnancy, and 2) by varying levels of maternal stress during pregnancy. We willalso examine levels of neonatal immune markers (antibodies, cytokines, chemokines) in relation to maternalCOVID-19 infection status and NDD in the child. This large scale and comprehensive study provides a uniqueopportunity to examine, in real-time, the impact of the coronavirus pandemic on child neurodevelopment in thefirst years of life, and establishes a novel framework to continue exploring the relationships between maternaland neonatal immune dysregulation and a range of neurodevelopmental disorders as they emerge over time.Findings will contribute to the development of prenatal and newborn screening for adverse neurodevelopment,ultimately enabling earlier intervention and primary prevention.",2020,2022,Kaiser Foundation Research Institute,152159,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C07046,3R01DK107585-05S1,Innate responses following infection with enteric microbes,"Abstract: As the rapidly unfolding COVID-19 pandemic claims its victims around the world, it has also inspired the scientificcommunity to come up with solutions to meet an urgent and unmet need -i.e., ameliorate the severity of Covid-19 and reduce mortality. Two obstacles make that task difficult-First, the pathophysiology of Covid-19 remainsa mystery; the emerging reports generally agree that the disease has a very slow onset and that those whosuccumb typically mount a 'cytokine storm', i.e., an overzealous immune response. However, despite beingimplicated as a culprit behind the observed mortality and morbidity in COVID-19, we know virtually nothing aboutwhat constitutes (nature, extent) or contributes to (cell or origin) such an overzealous response. A significantnumber of patients have GI symptoms. The treatment goals in COVID-19 have been formulated largely as a 'trialand error'-approach; this is reflected in the mixed results of the trials that have concluded. Second, the processof drug discovery is comprised of time-consuming steps; to avoid delays, we need to define the nature of thefatal cellular response before deciding how to model it in animals or matching therapeutics to curb it. Our preliminary work has helped us define the aberrant host cellular response in COVID-19. We usedmachine learning tools that can look beyond interindividual variability to extract underlying gene expressionpatterns within complex data across multiple cohorts of viral pandemics, including COVID-19. The resultantpattern, i.e., signature, was subsequently exploited as a predictive model to navigate COVID-19 for GIsymptoms. Surprisingly, the 166-gene signature was conserved in all viral pandemics, including COVID-19,inspiring the nomenclature-- (ViP)-signature. The ViP signature identified and predicted the disease severity ofSARS-CoV2-infected patients. We hypothesized that the ViP signature provides a quantitative and qualitativeframework for titrating the cellular response in viral pandemics and could serve as a powerful unbiased tool inour armamentarium to vet candidate drugs rapidly. In this proposal, our predicted model, experimental datasetsand the information from published literature will be used to screen drugs/nutritional components/probiotics inthe GI organoid derived monolayers in a semi-HTP format. We will experimentally validate the effect of thetherapeutics predicted in ViP gene signature of the host. The following two aims will provide a translational impacton the COVID-19 emergency.Aim 1: Identify the gastro-intestinal pathogenic pathways during COVID-19.Aim 2: Determine the impact of drugs, nutrients and supplements in gut-in-a-dish model of COVID-19.Impact: This proposal will identify the gastro-intestinal pathways (in healthy and patients with chronic diseases)involved in the GI symptoms of COVID 19 and provide new treatment options in COVID-19.",2020,2021,University Of California-San Diego,354469,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis | Pre-clinical studies",2016 +C07047,3U01HL146333-02S3,MWCCS Covid-19 Supplement Activities,"Abstract: COVID-19 cases continue to rise, with over 3,000,000 cases and 130,000 deaths in the US and almost 12million cases worldwide to date. Manifestations of SARS CoV-2 infection range from asymptomatic to mild,moderate, or severe disease, and primarily affects the lung, but increasing data suggests involvement of otherorgan and blood systems. Studies document more severe disease and higher mortality among people who areolder and/or have co-morbidities, such as hypertension, diabetes, obesity, and chronic lung disease. However,there is a paucity of data regarding the acquisition, occurrence and severity of infection among people with HIV(PWH). There is also little data to guide prevention and treatment recommendations for this population, manyof whom are older and have comorbidities that may increase not only their risk for acquiring infection, but alsothe morbidity and mortality among those who acquire infection. Moreover, early reports suggest substantialracial disparities in US COVID-19 rates, with increases in mortality among African Americans. The MACS-WIHS Combined Cohort Study (MWCCS), the largest and longest-running observational cohort of men andwomen living with or at risk for HIV in the US provides a unique opportunity to address important knowledgegaps in the acquisition, occurrence, severity and outcomes of COVID-19. The MWCCS is a geographically andracially/ethnically diverse cohort of aging men and women with a high prevalence of risk factors for progressionto severe COVID-19 disease including hypertension, diabetes, obesity, and smoking. The MWCCS has a richbiorepository of specimens, collects rigorous clinical measures including pulmonary, cardiac, kidney,neurocognitive, and physical function, body composition and has performed cohort-wide genome associationstudies. The overarching goal of this application is to understand the impact of the COVID-19 epidemic amongUS men and women with or at risk for HIV infection and to evaluate host factors that contribute to diseaseacquisition, expression, severity and recovery. The proposed studies will determine COVID incidence, short-term and long-term clinical outcomes, including thrombotic and pulmonary sequelae, and how racial andgeographic disparities; immune and genetic risk factors impact these outcomes in the MWCCS.",2020,2026,University of California-Los Angeles,110256,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2019 +C07048,3R01DK123446-01S1,Microbial and metabolomic profiling of the intestinal microenvironment distinguishing patients with mild and severe COVID-19 symptoms.,"Project Summary: The COVID-19 pandemic currently has infected over 4 million people worldwide and led to over 300,000 deaths.These numbers continue to grow and with an anticipated resurgence in the fall and winter months. It is now clearthat SARS-CoV-2 can enter the gastrointestinal (GI) tract, that it can bind to the ACE2 receptor abundantlyexpressed on intestinal epithelial cells, that it can be isolated live from stool, and that it sheds in the stool forseveral weeks after COVID-19 symptom onset. This information combined with the observations that GImanifestations of the disease, such as nausea and diarrhea, appear to be on the rise, place an urgent need formore clearly understanding the intestinal microenvironment in patients with COVID-19. This broad objective willnot only allow for more tailored treatment for patients with GI manifestations currently diagnosed with COVID-19, it will also help to understand whether a perturbed GI tract as a result of COVID-19 may lead to later GIpathology. Perhaps most importantly, this objective will help understand the factors that influence degree ofSARS-CoV-2 GI persistence and shedding in stool, which directly relate to the potential of fecal-oraltransmission. This proposal specifically addresses these objectives by examining whether the extensiveantibiotics administered to COVID-19 patients are creating unintended effects on the GI tract that result in afavorable environment for SARS-CoV-2 infection and persistence in the gut. The principle of competitiveexclusion has been demonstrated in the human GI tract in multiple publications using both oral and intravenousantibiotics, whereby the suppression of the total bacterial community and/or specific members, can result inincreased colonization by fungi, viruses, and antibiotic-resistant bacteria. Among the many roles of the gutmicrobiota, one fundamental role is to provide colonization resistance against foreign invaders. We do not yetknow how this microbial ecology plays out in the context of SARS-CoV-2. We hypothesize that antibioticperturbation of the gut microbiota and its metabolome in COVID-19 patients results in increased load andpersistence of SARS-CoV-2 in the intestines, and intestinal inflammation. We believe this may reflect diseasestage/severity. As a result, we anticipate findings will be rapidly translated to govern clinical managementof antimicrobials in patients as well as provide insight into pathways that influence transmission,development and resolution of COVID-19. Using biobanked specimens from COVID-19 patients that we haveprospectively collected, we will test our hypotheses in the following specific aims: Aim 1. Determine therelationship between bacterial and fungal intestinal communities and SARS-CoV-2 viral load longitudinally inSARS-CoV-2 positive and negative patients, with and without exposure to different antibiotics, and Aim 2.Determine whether alterations to the gut microbiome is reflected in an altered metabolite and inflammatoryprofile.",2020,2024,Cedars-Sinai Medical Center,371859,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Supportive care, processes of care and management | Adverse events associated with therapeutic administration",2020 +C07049,3R01HD100022-02S2,Maternal obesity and inflammation as drivers of maternal morbidity in COVID-19,"PROJECT Summary: While substantial attention on COVID-19 in pregnancy has been focused on whether verticaltransmission occurs, COVID-19 is also associated with severe maternal morbidity and maternalmortality. How pregnancy-specific immune changes impact the response to SARS-CoV-2 and thetrajectory of COVID-19 illness remains unknown. Similarly, it is not understood how maternal obesity,one of the most widespread maternal comorbidities, influences risk for severe disease. Recent worksuggests that the cytokine storm pathophysiology of severe COVID-19 may be mediated by monocytesand macrophages. Our laboratory's focus on maternal obesity and its impact on pro-inflammatorymacrophage priming in pregnancy therefore positions us well to answer these pressing scientificquestions. In light of the recent projection that millions of pregnant women will be exposed to COVID-19, understanding mechanisms underlying severe disease in pregnancy is an urgent public healthconcern.""Fetal Brain-Placental Immune Activation in Maternal Obesity"" is a pre-clinical R01 that tests thehypothesis that maternal obesity-associated inflammatory priming of fetal brain microglia and residentplacental macrophages or Hofbauer cells is a targetable mechanism underlying offspring cognitivedeficits. A key translational aspect of the funded project is to determine whether Hofbauer cellsrepresent a novel biologic surrogate for fetal brain microglial reactivity in the setting of maternal obesity.This administrative supplement proposal aims to test a maternally-focused hypothesis based on thesame premise: that maternal obesity will potentiate maternal inflammatory response to SARS-CoV-2infection by priming maternal monocytes and placental macrophages to overrespond to the virus, andthat maternal peripheral monocyte and placental Hofbauer cell reactivity can be used as a riskassessment or biomarker for COVID-19 disease severity. Here we propose to expand the ex vivo cellstimulation experiments in Aim 1a to include stimulation of SARS-CoV-2-exposed and unexposedhuman maternal peripheral monocytes with toll-like receptor ligands, and to examine the impact ofobesity on maternal monocyte response to SARS-CoV-2. We also propose to expand the single-cellRNA-sequencing experiments in Aim 1b to include human Hofbauer cells exposed and unexposed toSARS-CoV-2 and maternal obesity, to determine whether these exposures induce pro-inflammatoryalterations in Hofbauer cell programs. Together, these experiments will generate key insights into howmaternal obesity and associated priming of maternal monocytes and placental macrophages may drivematernal morbidity in the setting of COVID-19. Monocyte-macrophage priming can be used not only toidentify women at risk for morbidity, but are targetable mechanisms that can inform novel therapies.",2020,2022,Massachusetts General Hospital,175254,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2019 +C07050,3R01AG062690-02S1,Individual differences in dementia spousal caregiver burden: A biobehavioral approach revision,"Abstract: The outbreak of SARS-Cov-2 virus has exasperated the vulnerability of dementia spousal caregivers, as well asthose with Alzheimer's disease or related dementias. SARS-Cov-2 is a highly contagious virus that can causesevere respiratory problems and even death. Older adults and people of all ages with underlying comorbiditiesare considered to be at ""high-risk"" for severe illness from COVID-19. During this pandemic, dementia spousalcaregivers are tasked with the burden of keeping their spouse safe from getting sick and even dying from COVID-19, while simultaneously performing their typical caregiving responsibilities. The vast majority of dementiaspousal caregivers and their spouses with dementia are over sixty-five years of age, the age bracket that putspeople at most risk for COVID-19 disease complications and mortality. Social distancing guidelines make up alarge proportion of the current prevention recommendations; thus, loneliness and other negative emotions willlikely be frequent and more intense than usual. The proposed competitive revision builds upon the primary aimsof the parent grant (R01AG062690) by using attachment theory as an overarching theoretical framework tounderstand dementia spousal caregiver risk and resilience in light of coronavirus disease 2019 (COVID-19disease). The proposed research directly addresses several objectives from the PA-18-935, NOT-AG-20-022.Capitalizing on the dementia spousal caregivers who will take part in the parent study, we propose to collectadditional data for one week each month for three months. We will collect this data using ecological momentaryassessment methods, while passively assessing location, activity, autonomic activity, and sleep via smartphoneand smartwatch technology. We aim to understand how emotions, assessed in real-time in the naturalenvironment, affect the extent to which AD spousal caregivers adaptively navigate the challenges associatedCOVID-19. We will also aim to determine how relatively stable individual difference patterns that originate frompeople's close relationship histories (i.e., attachment orientations) inform risk and resilience. As an exploratoryhigh risk/high reward aim, we will evaluate if dynamic risk prediction models and machine learning approachescan incorporate passively collected information (i.e., location, heart rate, heart rate variability, activity, sleep) withinformation that we learn from our primary aims, to yield a detailed and sophisticated understanding of real-worlddynamics that predict three critical COVID-19 specific outcomes: social distancing adherence, social distancingself-efficacy, and caregiver self-efficacy. By understanding patterns of risk and resilience, intervention scientistswill be better able to identify at-risk AD spousal caregivers. The proposed research would advance ourunderstanding of how AD spousal caregivers can reduce illness exposure for themselves and those they carefor in perhaps the most comprehensive, detailed, real-time, real-world investigation of social distancing in ADspousal caregivers to date.",2020,2024,Rice University,493162,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience","Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings | Approaches to public health interventions",2019 +C07051,3P50CA107399-13S1,Transfer of COVID-19 Immunity Between Allogeneic Transplant Donors and Recipients,"The novel coronavirus, SARS-CoV-2, the agent causing COVID 19 respiratory syndrome has caused a global pandemic, with a toll of significant morbidity and mortality. SARS-CoV-2 infection is expected to be very serious in the vulnerable population of non-Hodgkin lymphoma (NHL) patients, who received an allogeneic hematopoietic stem cell transplant (HCT), as a curative procedure for relapsed NHL (Project 1). Due to their immunocompromised status, HCT recipients are at increased risk for severe COVID 19 disease, including respiratory complications and exacerbated lethality of the infection. There are still critical gaps in our knowledge of the immune response and its role in clinical manifestations of COVID 19, in HCT recipients. In transplant practice, we know that donor immunity can often be transferred to the recipient as part of the graft. Hence, our goal is to investigate if viral immunity is transferred from the HCT donor, who was exposed to COVID 19, to the HCT recipient. SARS-CoV-2 donor derived immunity could benefit the recipient, contributing to reduced COVID 19 morbidity and mortality, and improving HCT outcomes in high risk NHL recipients. Our previous and ongoing studies with cytomegalovirus (CMV), a respiratory virus causing major post-HCT complications, laid the groundwork for the design of the current proposal. Data from our group demonstrated that donor-derived CMV specific immunity can benefit post-transplant outcomes, by reducing the duration and recurrent need of antiviral treatment in the HCT recipient. Additionally, vaccinating donor and/or recipient posttransplant with Triplex, a CMV vaccine developed by our team at City of Hope (COH), augments protective antiCMV immunity. These clinical data lead to our hypothesis that a HCT donor, recovering from COVID 19, will transfer protective antiviral immunity to the HCT recipient. Guided by our established experience in transplant immunology, we propose a one-year observational study to pursue the objective of characterizing levels, quality, and duration of SARS-CoV-2 immunity, which could protect against viral infection when transferred from matched (sibling or unrelated) and half-matched (haploidentical) family donors to HCT recipients. Specimens from SARSCoV-2 seropositive donor/recipient pairs will be extensively assessed for the presence of functional antiviral immune responses. The immune monitoring study will focus on the six months interval post-HCT, when immunity in HCT recipients is mostly donor derived, to assess whether SARS-CoV-2 immunity transfer occurs, and contributes to protection against serious COVID 19. Our proposed research will broadly impact the transplant field, by providing critical information on the role of protective donor-derived SARS-CoV-2 immunity in HCT recipients, during immune reconstitution. This study will also lay the ground work for the use of a novel COH COVID 19 vaccine in the transplant setting, with the goal of amplifying the HCT donor immune response to SARS-CoV-2, and/or eliciting protective immunity by immunizing the recipient.",2020,2023,Beckman Research Institute/City Of Hope,176000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management",2004 +C07052,3P42ES031007-01S2,The UNC Chapel Hill Superfund Research Program (UNC-SRP) (2),"Abstract: This proposal is being submitted as an Emergency Competitive Revision for the University of North Carolina(UNC) Superfund Research Program (SRP) in the context of the Coronavirus Disease 2019 (COVID-19)pandemic. We focus on inorganic arsenic (iAs), the #1 contaminant of the Agency for Toxic Substances Registry(ATSDR) contaminating drinking water around the globe. iAs is toxic to many organs in the body, acting as acarcinogen, diabetogen, neurotoxicant, and immunosuppressant. Notably, in several of the North Carolinacounties where iAs levels in drinking water are high, the prevalence of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection is also high, indicating that a co-exposure to iAs and SARS-CoV-2 likelyoccurs. This co-exposure to iAs on the susceptibility to SARS-CoV-2 infection and COVID-19 severity has neverbeen studied. The goal of this proposal is to characterize the interaction between iAs exposure and SARS-CoV-2 infection using differentiated primary human nasal epithelial cells, an established in vitro model for respiratoryinfections, and a novel humanized hAS3MT mouse strain, in which the metabolism of iAs and disposition of itsmetabolites resemble those in humans. In a strong, transdisciplinary approach, we will use differentiatedprimary human nasal epithelial cells and a humanized hAS3MT mice to test the hypothesis that chronicexposure to iAs enhances susceptibility to SARS-CoV2 infection and severity of COVID-19. Whileintegrating human and mouse models, we will also examine the role of sex and genetic background on thedisease outcome. The two new additional Aims include: (Aim 1) Identify the effects of iAs and its metabolites onSARS-CoV-2 infection in differentiated primary human nasal epithelial cells; and (Aim 2) Characterize the effectsof iAs exposure on SARS-CoV-2 MA infection and COVID-19 outcomes in hAS3MT mice. In Aim 1, we test thehypothesis is that exposure to iAs or its metabolites enhances susceptibility to and severity of SARS-CoV-2infection in the human nasal epithelial cells. In Aim 2, we will compare immune response, viral titer, lungpathology and mortality in hAS3MT mice exposed to iAs in drinking water (0, 40, or 400 ppb) and infected witha mouse-adapted SARS-CoV-2 that has been recently created at UNC Chapel Hill. To assess the role of sexand genetics, we will use male and female hAS3MT mice with C57BL/6NCrl and 129S6/SvEvTac backgrounds.The proposed research utilizes novel laboratory models that are available only at UNC and are uniquely suitedfor studies of the interaction between environmental iAs exposure and SARS-CoV2 infection. The proposedresearch addresses a critical need for understanding of the interaction between a widespread environmentalexposure and a pandemic infection that affects hundreds of millions of people worldwide.",2020,2021,University of North Carolina at Chapel Hill,464251,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity | Disease pathogenesis",2020 +C07053,3U01HL123336-06S2,REPRIEVE COVID-19 Administrative Supplement,"Project SummaryIn response to NOT-HL-20-757, Notice of Special Interest (NOSI): Availability of Administrative Supplementsand revision Supplements on Coronavirus Disease 2019 (COVID-19), and PA-18-591 AdministrativeSupplements for existing NIH Grants and Cooperative Agreements, the enclosed administrative supplement,leveraging parent grant U01 HL123336, is submitted for consideration. Understanding COVID-related CVcomplications in at-risk populations represents an urgent national priority. Retrospective case series haveshown that among patients in the general population hospitalized with COVID-19, approximately 20 to 30%evidence myocardial injury, which is associated with adverse outcomes including cardiac dysfunction,arrythmia, hypercoagulable events, and death. In addition, significant evidence exists for endothelial andvascular dysfunction related to COVID-19, related to membrane uptake via ACE-2 or other mechanisms.People with HIV (PWH) already face increased risk of myocardial infarction and heart failure as compared withthe general population. How COVID-19 affects CV morbidity and mortality among PWH remains unknown andpreventive/therapeutic strategies have yet to be identified. We propose to leverage the REPRIEVE trial - thelargest international randomized trial focused on preventing HIV-associated CV disease - to address criticalknowledge gaps regarding SARS-CoV-2 infection and COVID-related CV complications among PWH. Studying7,700 PWH ages 40-75 across 5 continents, we will focus on three interrelated but independent key topics:epidemiology, host factors, and protective strategies. In this regard, statins have pleiotropic effects andpotently reduce vascular inflammation and improve endothelial function, The results of the supplement willprovide critical information on HIV and COVID-19, and conversely critical effects of statins to mitigate effects ofthe SARS-Co-V2 virus on cardiovascular disease and endothelial function, and MACE. These results will bebroadly generalizable to the large population of HIV patients simultaneously at risk for COVID-19 and CVD andalso to other populations at risk for CVD experiencing COVID infection.",2020,2021,Massachusetts General Hospital,1210912,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Clinical trials for disease management | Clinical trial (unspecified trial phase),2014 +C07054,3UH3TR002158-04S1,Cellular and Molecular Mechanisms of COVID-19 Mediated Kidney Injury,"PROJECT SUMMARY / Abstract: The ongoing coronavirus 2019 (COVID-19) pandemic is caused by severe acute respiratory syndromecoronavirus 2 (SARS‑CoV‑2), and has led to over one million reported cases, significant morbidity andmortality, and extensive economic and societal disruption. The development of the disease has shown to leadto complications kidney failure. It is becoming clear that multiple mechanisms of kidney involvement in COVID-19 infection are operative. Between 30 and 40% of severely infected COVID-19 patients develop Acute KidneyInjury with a high proportion requiring dialysis therapy in the Intensive care Unit. Moreover, evidence frombiopsy and autopsy studies is emerging that kidney podocytes, proximal tubular epithelial cells and endothelialcells may become infected with SARS‑CoV‑2. Emerging data demonstrate that COVID-19 podocyte injuryleads to nephrotic syndrome, proximal tubular involvement leads to acute kidney injury, and endothelialinvolvement leads to thrombotic microangiopathy - thus COVID-19 kidney involvement can have proteanclinical manifestations, analogous to the effects of HIV infection on the kidney. No specific treatment iscurrently validated for COVID-19 related kidney disease, and understanding the cell-specific molecularprocesses associated with COVID-19 in patients with kidney disease and diabetes can have a significantimpact on public health. A better understanding of the mechanism will foster development of effective therapiesbeyond the supportive care in the intensive critical care unit, which is already critically important as many ofthese patients require dialysis-related therapy. Our group has pioneered the development of `human kidney-on-a-chip' microphysiological systems (MPS), which recapitulate critical aspects of kidney physiology, assessthe mechanisms and response to injury, and test reparative mechanisms. We will deploy our existing MPS tounderstand the cellular and molecular mechanisms of COVID-19 mediated kidney injury, and test therapeuticstrategies to prevent kidney injury and kidney failure due to SARS‑CoV‑2.",2020,2022,University Of Washington,300384,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis,2017 +C07055,3U01CA232826-03S2,Leveraging an electronic medical record infrastructure to identify primary care patients eligible for genetic testing for hereditary cancer and evaluate novel cancer genetics service delivery models,"SUPPLEMENT Abstract: This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-042. The application is a proposed administrative supplement to the University of Utah (Utah)/New YorkUniversity (NYU) U01 entitled ""Leveraging an electronic medical record infrastructure to identify primary carepatients eligible for genetic testing for hereditary cancer and evaluate novel cancer genetics service deliverymodels"" (U01 CA232826). The parent U01 is employing a replicable electronic health record (EHR)-basedclinical decision support infrastructure to: (i) identify unaffected primary care patients who qualify for cancergenetics services based on current guidelines in the Utah and NYU healthcare systems (Aim 1); and (ii)compare two models of cancer genetics services delivery for 1,920 of these unaffected primary care patients ina randomized controlled trial (Aims 2 and 3). The parent trial will examine how race and ethnicity modify theeffects of the cancer genetics services delivery models. The landscape for delivering genetics services haschanged substantially due to the COVID-19 pandemic, and our pilot data suggest that patients' uptake ofcancer genetic testing and access to cancer screening has been adversely affected. This supplement wouldprovide us with an unparalleled opportunity to investigate COVID-19 impacts in two study sites with verydifferent pandemic contexts. We propose the following Supplemental Aims: (1) Characterize healthcareexperiences related to COVID-19 among the cohort of 22,208 primary care patients identified as being atincreased risk for hereditary cancer; and (2) Investigate how COVID-19 impacts primary care patients'decisions about and utilization of cancer genetics services. To address Supplemental Aim 1, we will abstractEHR data to investigate COVID-19 diagnosis, SARS-CoV-2 testing, and delays in cancer screening in theidentified cohort. Among the subset of the cohort invited to participate in the trial, we hypothesize that havingbeen diagnosed with or hospitalized for COVID-19 or having had a cancelled cancer screening will negativelyaffect trial participation. We will also investigate differences in these COVID-19 experiences by study site (Utahvs. NYU) and race/ethnicity. To address Supplemental Aim 2, among participants in the parent trial, we willexamine how the health, psychological, and financial impacts of COVID-19 affect decisions about andutilization of cancer genetic counseling and genetic testing using a combination of clinic records andquestionnaire data. Based on pilot data, we hypothesize that those having higher self-reported health,psychological, and financial impacts of COVID-19 will be less likely to complete cancer genetic testing. We willexamine how the effects of COVID-19 are modified by study site (Utah vs. NYU) and race/ethnicity. Together,the supplemental aims will allow us to build a comprehensive picture of how COVID-19 has affectedparticipation in and outcomes of the parent trial. The proposed supplement would also allow us to examinewhether COVID-19 is widening disparities in use of cancer genetics services by race and ethnicity.",2020,2023,University Of Utah,160971,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C07056,3R01AG063954-02S1,Establishing the science behind Alzheimer's recruitment registries: opportunities for increasing diversity and accelerating enrollment into trials,"PROJECT SUMMARY/ABSTRACTWith the singular focus on COVID-19 in both the media environment and in the everyday lives of most people,it is not clear how perceptions of other health conditions may shift, especially among older adults who areparticularly vulnerable to COVID-19. Research demonstrates a tendency for individuals to allow their attitudestowards one salient issue to impact their attitudes and behaviors towards unrelated, but similar other issues(i.e., spillover effects). Given the emphasis on science and research in COVID-19 discourse, it is important toassess whether older adults' pandemic experiences may ""spillover"" to their perceptions of scientific research inways that may affect their willingness to participate in Alzheimer's disease (AD)-related research efforts. In thisproject, we propose to examine how information sources on COVID-19 and the larger context of the pandemicinfluence older adults' perceptions of scientific research and AD, adherence to recommended COVID-19prevention behaviors, and whether these perceptions vary by racial/ethnic group. This research is critical todetermine whether COVID-19 spillover is changing how individuals perceive both AD as a health risk and callsto participate in AD research such as enrolling in recruitment registries. Grounded in Spreading ActivationTheory and the Reasoned Action Approach (RAA), we propose two aims. First, to determine the extent towhich COVID-19 news coverage and lived experiences change perceptions of scientific research andwillingness to participate in AD-related research, we employ a mixed methods approach using surveys andcontent analysis. We conduct a series of repeated cross-sectional surveys over a period of 12 months tomonitor how changes in the pandemic and in news coverage may be related to attitude shifts about researchgenerally and specific to AD and AD risk. Survey data will be collected across 12 waves from a nationalsample stratified by the race groups that correspond to the groups of interest in the parent award (white,Hispanic, Black). Data are collected monthly, which allows for capturing perceptual shifts as the COVID-19situation changes rapidly. A theory-driven content analysis of news coverage from main news sources,coinciding with the surveys, will also be conducted with the goal of understanding the extent and nature ofCOVID-19 information and misinformation, including topics such as racial disparities in COVID-19 morbidityand mortality and emphasis on older adults and racial minorities as vulnerable populations. The second aimidentifies relevant psychosocial determinants (attitudes, norms, efficacy/control) of subsequent COVID-19-related health behaviors (i.e., preparation, prevention) for older adults using the RAA. We collect a follow-upwave of data (Wave 2) from the Wave 1/Baseline from the repeated cross-sectional surveys and predict howeffects of exposure to media and interpersonal messages are mediated through attitudes, norms, and efficacyto predict subsequent COVID-19 recommended behaviors. Together these two aims allow for a test of COVID-19 spillover into AD-related attitudes and willingness to participate in AD research.",2020,2024,Banner Health,387949,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2019 +C07057,3R03AG063290-02S1,MAGL PET tracer-guided prognosis and neuroprotective therapy for Alzheimer's disease,"Project Summary: The 2019 novel coronavirus (SARS-CoV-2; COVID-19) has spread rapidly in the global level sinceits recent identification in patients with severe pneumonia. To date, there is no approved therapy/vaccine to treathuman coronaviruses. For instance, there is tentative evidence of Remdesivir for alleviating COVID-19 symptom asauthorized for emergency use by the FDA, which is still being tested in advanced clinical trials worldwide. Favipiravir is an anti-viral drug developed by Toyama Chemical of Japan. It is a pyrazinecarboxamide derivativethat has been reported to show activities against RNA viruses in vivo and in vitro. Favipiravir is phosphoribosylated tofavipiravir-ribofuranosyl-5′-triphosphate, which then recognized as a substrate by RNA-dependent RNA polymerase(RdRp) and inhibits the RNA polymerase activity. Favipiravir is active against influenza A/B/C, including oseltamivir-resistant variants. Some preclinical research has indicated that Favipiravir may have efficacy against Ebola. InFebruary 2020, Favipiravir was being studied in China for COVID-19 treatment. The results showed that patients whohad tested positive for COVID-19 and given the drug got a negative virus test back four days after treatment. Lungconditions improved in about 91% of patients taking Favipiravir. In March 2020, a pilot trial suggested that Favipiravirwas effective in treating COVID-19 and further clinical trials are underway in Japan (Phase III), Italy (Phase III) andthe U.S. (Massachusetts, Phase I). Although Remdesivir and Favipiravir both target RdRp, it is worth mentioning that,compared to Remdesivir, Favipiravir is a fluorinated anti-viral drug, which represents a unique opportunity for studyingdosing and target engagement in vivo using its 18F-isotopologue by positron emission tomography (PET). Although preliminary positive outcome has been made in COVID-19 patients with Favipiravir treatment, given thatthe study was only able to monitor drug changes in plasma levels following treatment, we hypothesize that anti-viraltherapy using non-invasive imaging tools could provide the direct and real-time correlation between drug treatmentand disease stages via whole body distribution and target occupancy of Favipiravir in organs of interest, such as thebrain. PET can provide such information via targeted radioactive molecules (radiotracers; in this work, the tracer is[18F]Favipiravir), which will be highly advantageous in monitoring [18F]Favipiravir exposure in the central nervoussystem under neurodegenerative conditions comorbid with blood-brain barrier dysfunction/neuroinflammation.Neurodegenerative diseases, including Alzheimer's disease, are known to disrupt brain integrity and function, thusleading to an increase risk of COVID-19 infection, neuroinflammation and immune compromise, as well as safetyconcerns for dose selection for anti-viral therapy. In this work, we hypothesize that [18F]Favipiravir can be re-purposedas invaluable pharmacokinetic and/or pharmacodynamic imaging markers for clinical development of anti-viraltherapeutics by enabling target occupancy studies in highly-vulnerable brain affected by COVID-19. Such criticalinformation would substantially and rapidly improve our design of anti-viral treatment plans, particularly for treatingpotential SARS-CoV-2 reservoirs in the CNS.",2020,2021,Massachusetts General Hospital,163671,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2019 +C07058,3P60AA009803-27S3,LSUHSC-NO Comprehensive Alcohol-HIV/AIDS Research Center,"Abstract Administrative Supplement Research Component 1 (RC1) Comprehensive Alcohol ResearchCenter. Community and Interpersonal Stress, Alcohol, and Chronic Comorbidities among PLWH.Louisiana had the third highest rates of SARS-CoV-2 cases and the second highest deaths per capita in thecountry during the peak of the COVID-19 pandemic. The alarming high rate of mortality in New Orleans led tostrict government issued mandates for social distancing, self-quarantine, and shelter-in-place measures addingchallenges like unemployment, loss of social networks, fear, and decreased access to personally deliveredhealthcare to the most vulnerable individuals. These stressful factors negatively impact pre-existing symptomsof stress, anxiety, and depression and may have unwanted consequences that contribute to morbidity andmortality of vulnerable populations. Persons living with HIV (PLWH) have an excessively high rate of exposureto chronic and lifetime social stressors, that are linked to elevated rates of poorer mental health includingdepressive disorders, alcohol use disorders (AUD), and post-traumatic stress disorder (PTSD). Alcoholconsumption tends to increase during times of duress and uncertainty, and alcohol is often misused to copewith stress, anxiety, and other uncomfortable emotions. Psychiatric comorbidities decrease adherence toantiretroviral therapy and increase risk for substance use that together may increase risk for comorbidities ornegatively impact disease progression particularly in aging PLWH. Heightened psychosocial and physiologicalstress among PLWH is associated with poorer immune status, increased viral load over time, faster diseaseprogression, and higher rates of mortality. Our overarching hypothesis is that PLWH with AUD experiencegreater psychobehavioral and biological consequences of the COVID-19 pandemic. This administrativesupplement proposes studies within the scope of those proposed in Specific Aim 1 of RC1: To examine theimpact of neighborhood and interpersonal stress on alcohol use and its associated comorbidities inPLWH. This aim tests the hypotheses that a) Contextual stressors will be associated with alcohol use as wellas clinical comorbidities (e.g., mental health, cardiometabolic conditions, neurocognitive impairment, andfrailty) and b) Alcohol use mediates the relation between stress and clinical comorbidities. We propose toobtain self-reported measures of stress, anxiety, depression, and alcohol use of PLWH and HIV seronegativesubjects enrolled in our longitudinal New Orleans Alcohol Use in HIV (NOAH) study during the pandemic.Quantitative and qualitative data collected during the government mandated shelter-in-place and within 2months of reopening of the city will be integrated with individual level demographic, clinical (includingserological immunological evidence of exposure), behavioral (alcohol use), and disease-specific (HIV viralloads and CD4/CD8 counts) data to determine the impact of COVID-19 related stress on drinking behavior,adherence to ART, and manifestation of anxiety symptoms. Moreover, we will elucidate the interaction ofCOVID-19 related stress and alcohol drinking during this stressful period with risk for comorbidities in PLWHand HIV seronegative individuals. These studies directly integrate in the overall framework of our center andleverage existing infrastructure to maximize data collection during this unique timeframe.",2020,2024,Lsu Health Sciences Center,102458,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,1996 +C07059,3R01AA025995-03S1,Proximal Effects of Alcohol on Same-Sex Intimate Partner Violence,"Research indicates that stress and its concomitant negative mental health and physical health outcomes aredirect results of pandemic episodes1. Stress related to COVID-19 is no exception2 3 4. We argue that this stress -which we term COVID-19 stress - is temporally and proximally related to increases in HED and IPVperpetration in sexual and gender minority (SGM) couples. This focus on SGM couples is purposeful. Becausethe COVID-19 pandemic poses greater economic, social, and personal challenges for SGM people 5, they mustcope with both COVID-19 stress and well-established minority stressors 6. Thus, they are more likely to engagein maladaptive coping behaviors, including HED and IPV, relative to cisgender, heterosexual people.There are myriad weaknesses in the rigor of research on HED and/or IPV in SGM couples, which include: (1)few studies which distinguish between sex assigned at birth, sexual orientation, and gender identity; (2)inadequate sample sizes of gender minorities; (3) poor operational definitions, and thus weak measurement, ofHED and IPV; and (4) dependence on cross-sectional study designs which cannot model the temporal relationbetween relevant risk factors and HED or IPV perpetration. Our team is uniquely positioned to address theseweaknesses via two aims: (1) evaluate the impact of COVID-19 stress and SGM stress on HED and IPVperpetration, and (2) evaluate a brief, low-resource intervention to mitigate the effects of these stressors.These aims will be achieved by using a longitudinal measurement burst daily diary design that includes four 14-day bursts with three 14-day intervals between each burst. During Intervals #2 and #3, participants will berandomly assigned to receive (1) two daily CBT-based text messages that focuses on emotion regulation,distress tolerance skills, and/or alcohol reduction strategies, (2) two daily text messages that serve as anattention control, or (3) no text messages. Our sample of 240 couples will be comprised of 120 couples in whichboth partners identify as cisgender and a sexual minority and 120 couples in which at least one partneridentifies as a gender minority, meaning one's gender identity is non-congruent with the sex they wereassigned at birth. Effects will be examined within an Actor-Partner Interdependence Modeling framework,which will allow for valid analysis of both partners' intersecting identities as well as risk and resilience factorsat the individual- and couple-level.Expansion of the parent grant via the proposed urgent competitive revision has high potential to inform howpandemic stress contributes to etiological models of alcohol-related IPV perpetration in SGM couples andinform a culturally-sensitive, low burden, and easy to disseminate intervention to mitigate these effects criticalduring a pandemic when access to care is limited. As such, this project has high potential to impact publichealth, particularly in vulnerable SGM communities during a pandemic.",2020,2023,Georgia State University,151659,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2018 +C07060,3R01AA026575-02S1,Preventing Alcohol Misuse among Young Adult Veterans through Brief Online Intervention,"Project Summary/Abstract This application is being submitted in response to NOT-OID-20-097, Availability of AdministrativeSupplements and Urgent Competitive Revisions for Research on the 2019 Novel Coronavirus and theBehavioral and Social Sciences. We are requesting an administrative supplement (PA-18-591) to expand Aim1 of the parent NIAAA project (online survey of 1,548 veterans outside of treatment settings) by addingadditional measurement waves to track changes in outcomes due to the COVID-19 pandemic. The primaryobjective of this proposed mixed-methods research study is to leverage our existing sample of veterans in thecommunity to examine changes in substance use, mental health, and social and economic health. We proposeto survey and interview participants for 18 months after their initial survey, with three follow-up surveys and twosets of qualitative interviews to assess behavioral, social, and economic health to learn more about how thepandemic has affected veterans outside of VA settings. Findings from this study can answer essentialquestions to better serve veterans, such as how COVID-19 has influenced substance use, how veteransscreening positive for mental health disorders have managed during the pandemic, and how changes in socialand economic health, such as changes in relationships, job loss, loneliness, and perceived stress, haveinfluenced changes in substance use and mental health symptoms over time.",2020,2023,University Of Southern California,165000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C07061,3R01DK112322-05S1,Dulce Digital-COVID Aware (DD-CA) discharge texting platform for US/Mexico border Hispanics with diabetes + COVID-19,"Project Summary: Hispanics, a group that shows higher type 2 diabetes (T2D) prevalence, and poor self-management andclinical outcomes, have been disproportionally adversely impacted by COVID-19. The California Department ofPublic Health reports that Hispanics make up 39% of California's population but an unprecedented 57% of theconfirmed COVID-19 cases. This devastating finding is especially notable on the US/Mexico border. Diabeteshas emerged as a leading risk factor for severe COVID-19 illness leading to hospitalization, is associated withgreater disease severity and mortality and is an independent predictor of intensive care placement andinvasive ventilation. It is becoming increasingly clear that maintaining good glucose control improves prognosisof COVID-19 among people with pre-existing T2D. However, social distancing, quarantine, and stay-at-home/lockdown guidelines may impact one's ability to maintain adequate glycemic control. Research isneeded to evaluate the effect and clinical outcomes of a flexible, easily adopted low cost digital interventionthat improves glucose excursions and provides urgently needed COVID-19 mitigation strategies, amongrapidly rising groups of high-risk Hispanics with poorly controlled T2D in US/Mexico border communities.Strong evidence from our parent grant Dulce Digital-Me, supports the use of technology (such as textmessaging) alone or in combination with coaching interventions as a viable and desired method of deliveringtailored diabetes self-management education and COVID awareness messaging to high-risk, underservedpopulations in a manner that is more convenient for both patients and staff while having the added benefit ofbeing cost-effective for health systems, especially within low resource settings. However, effectiveinterventions may encounter barriers which preclude guaranteed success upon implementation in the realworld. This project, taking place along the San Diego/Tijuana border, historically the busiest land port of entryin the Western Hemisphere, will assess the effect of providing an enhanced digital texting intervention-DulceDigital-COVID Aware (DD-CA) to N = 172 Hispanic patients with T2D upon discharge from a recenthospitalization. Key outcomes will assess the impact of DD-CA on hospital readmissions at 30 and 90 dayspost-discharge, glucose control and patient reported outcomes at 90 days post-discharge while also assessingCOVID status and the implementation process. Given that DD-CA offers the potential to address many of thepractical barriers to access and extend the reach of diabetes services, while additionally providing COVIDawareness support, it offers an ideal low-cost and flexible solution to reduce hospital admissions and re-admissions in US/Mexico border communities significantly and simultaneously affected by COVID-19 and T2D.Implemented in a typical hospital and post-discharge setting, it augments existing care team processes, thusproviding a valuable test of real-world effectiveness. More importantly, by helping to reduce existing inequitiesin access to diabetes and COVID-19 care, this program aims to improve health outcomes on a larger scale.",2020,2021,Scripps Health,306364,Human Populations,Other,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Post acute and long term health consequences | Barriers, PPE, environmental, animal and vector control measures | Communication",2016 +C07062,3R01CA207689-04S1,"Adapting and Implementing a Remote, Digital CRC Screening Intervention for Primary Care Practice in Response to COVID-19","PROJECT SUMMARYGuided by the Consolidated Framework for Implementation Research (CFIR), the overall goal of this proposedsupplement is to adapt the Meet ALEX intervention to patient concerns about CRC screening safety as a resultof COVID-19, pilot test in 2 new primary care clinics, and examine implementation of a remote intervention in apost-pandemic clinical environment. The COVID-19 pandemic is expected to exacerbate cancer screeninginequities among vulnerable patient populations. Through the parent grant, the research team has worked in 6UF Gainesville clinics to develop an efficient workflow and support infrastructure to address the CRC screeningneeds of vulnerable patient populations. Stool-based testing is now being recommended to reduce theforthcoming backlog of endoscopic and radiological CRC screening exams. The Meet ALEX intervention isideally situated to help mitigate CRC screening inequities for vulnerable patient populations by providingpatient education and in-home stool testing.In Specific Aim 1, we will expand implementation of the parent grant intervention, called Meet ALEX (AgentLeveraging Empathy for Exams) to 2 UF Jacksonville clinics that serve a predominantly Black/AfricanAmerican and Latinx patient population. We will also pilot test a modification that addresses patient concernsabout CRC screening safety related to COVID-19. We will examine whether tailoring the intervention to patientconcerns about COVID-19 alters self-reported preferences for CRC screening modality (ie, colonoscopy, homestool testing) and behavior (assessed via chart review) compared with patients who receive the existingintervention.In Specific Aim 2, we will describe facilitators and barriers associated with implementing Meet ALEX as a resultof COVID-19 through in-depth interviews with key stakeholders (ie, health care providers and clinic managers)from all implementing clinics (N=8) to understand changes to organizational processes and preferences forCRC screening, availability of remote counseling, and barriers and facilitators related to implementing digitalinterventions as a result of the pandemic.The results of this supplement will lead to the development of best practices for implementing digital cancerscreening interventions to reduce CRC inequities in primary care settings affected by COVID-19.",2020,2021,University Of Florida,152492,Human Populations,Black | Other | Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Policy research and interventions | Indirect health impacts | Health service delivery | Systemic/environmental components of capacity strengthening,2020 +C07063,3U01HL146208-02S4,"COVID-19 and the MWCCS: Pathophysiology, Impact and Outcomes","COVID-19 and the MWCCS: Pathophysiology, Impact and OutcomesAbstract: COVID-19 cases continue to rise, with over 3,000,000 cases and 130,000 deaths in the US[1] and almost 12million cases worldwide[2] to date. Manifestations of SARS CoV-2 infection range from asymptomatic to mild,moderate, or severe disease, and primarily affects the lung, but increasing data suggests involvement of otherorgan and blood systems.[3] Studies document more severe disease and higher mortality among people whoare older and/or have co-morbidities, such as hypertension, diabetes, obesity, and chronic lung disease.[4-7]However, there is a paucity of data regarding the acquisition, occurrence and severity of infection amongpeople with HIV (PWH). There is also little data to guide prevention and treatment recommendations for thispopulation, many of whom are older and have comorbidities that may increase not only their risk for acquiringinfection, but also the morbidity and mortality among those who acquire infection. Moreover, early reportssuggest substantial racial disparities in US COVID-19 rates, with increases in mortality among AfricanAmericans.[8] The MACS-WIHS Combined Cohort Study (MWCCS), the largest and longest-runningobservational cohort of men and women living with or at risk for HIV in the US provides a unique opportunity toaddress important knowledge gaps in the acquisition, occurrence, severity and outcomes of COVID-19. TheMWCCS is a geographically and racially/ethnically diverse cohort of aging men and women with a highprevalence of risk factors for progression to severe COVID-19 disease including hypertension, diabetes,obesity, and smoking. The MWCCS has a rich biorepository of specimens, collects rigorous clinical measuresincluding pulmonary, cardiac, kidney, neurocognitive, and physical function, body composition and hasperformed cohort-wide genome association studies. The overarching goal of this application is to understandthe impact of the COVID-19 epidemic among US men and women with or at risk for HIV infection and toevaluate host factors that contribute to disease acquisition, expression, severity and recovery. The proposedstudies will determine COVID incidence, short-term and long-term clinical outcomes, including thrombotic andpulmonary sequelae, and how racial and geographic disparities; immune and genetic risk factors impact theseoutcomes in the MWCCS.",2020,2026,University Of Pittsburgh At Pittsburgh,359561,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2019 +C07064,3R01CA202021-05S1,Control of Protein Synthesis by the UPS Under Stress,"Project SummaryFollowing its infection, SARS-CoV-2 utilizes cellular networks to enable its efficient replication. Key for its successin hijacking cellular systems of host cells lies in the takeover of the translational apparatus, whereby the virusrequires eukaryotic translation initiation complex 4F (eIF4F) activity. To this end, cap-dependent and eIF4F-driven viral genome RNA translation is essential for production of the viral proteins required for its replication.Notably, cancer cells rewire their RNA translational machinery, as often reflected by enhanced activity and/orexpression of eIF4F subunits leading to increased complex activity. Thus, SARS-CoV-2 and translationalperturbations in cancer may converge on cap-dependent translation and, in particular, on the eIF4F complex.Accordingly, a different degree of susceptibility to SARS-CoV-2 infection is expected in cancer cells based ontheir pre-rewiring of the RNA translation machinery. The underlying hypothesis of this proposal is that targetingcomponents of the eIF4F complex is expected to provide novel therapeutic modality for inhibition ofSARS-CoV-2 replication, while exerting anti-neoplastic effects across broad spectrum of cancers. To testthis, we will define the effectiveness of RNA translation modulators, we have developed, in attenuating SARS-CoV-2 effect on eIF4F activity in lung cancer cells susceptible to coronavirus infection. The effect of RNAtranslation modulators on SARS-CoV-2 infected lung cancer cells response to commonly used therapy will bealso assessed. This is anticipated to improve understanding of coronavirus biology in context of neoplasia andin long-term provide therapeutic modalities for cancer patients infected with SARS-CoV-2 or other coronavirusesanticipated to cause future pandemics.",2020,2021,Sanford Burnham Prebys Medical Discovery Institute,87750,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",,2016 +C07065,3R01DK121072-01A1S1,Optimization of the engineered 3D hepatic microenvironment enhances pluripotent stem cell derived hepatocyte,"Project summaryIn late 2019, COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and has rapidly impacted almost all countries around the world. Officiallydeclared a global pandemic by the WHO, COVID-19 is a worldwide emergency and bymillion United with directly , current in vitro model platforms are so distinct from human infection that they may not capture key components of viral infection or virus-host interactions. May 29, 2020, over 5.8 COVID-19 cases were reported with over 360,000 deaths globally. Although originating in China the States has emerged as an epicenter of this pandemic with over 1.75 million COVID-19 cases reportedover 103,000 deaths. Unfortunately there is no vaccine that can prevent SARS-CoV-2 infection or robustactiving antivirals that can mitigate infection or alter disease progression. MoreoverGiven this local, national, and global emergency our near-term goal is on the development of novel and robustexperimental cell culture models, virological tools, and to identify novel therapeutics for SARS-CoV-2 treatment.Our long-term goal is to elucidate the complex interactions and mechanisms underlying SARS-CoV-2 infectionand host response. Given that our institution has been at the center of the COVID-19 pandemic here in the U.S.we have generated a wide database of clinical data that has revealed that a high prevalence of initial COVID-19 presentations are with GI manifestations with over one-half of patients noted to have biochemical evidenceof liver injury at presentation. The impact of SARS-CoV-2 infection on hepatocellular and cholangiocytefunction remains unclear. To address these knowledge gaps we have generated several novel technologiesand have assembled a robust team with complimentary expertise in stem cell biology, tissue engineering andvirology, chemical screening and stem cell biology, and in virology/BSL3 expertise. We aim to identify drugcandidates that impact SARS-CoV-2 viral infection while we evaluate host-virus interactions.Our work is urgently needed given the impacts SARS-CoV-2 has had on our local, national, and globalcommunities and its potential impact on millions of people who already, or will in the future will developCOVID19 infection by shedding light on mechanisms, molecular targets, and potential drugs that could leaddirectly to the development of new antiviral treatments and therapies.",2020,2022,Weill Cornell Medicine - Cornell University,381375,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2020 +C07066,3R21HG010391-02S1,Urgent Supplement: Correcting genetic disorders using predictable CRISPR/Cas9-induced exon skipping,"Project Summary: The rapid spread of SARS-CoV2 presents an unprecedented challenge to urgently control diseasemorbidity, mortality, and spread. Antiviral drugs including remdesivir, favipiravir, and EIDD-2801 haveemerged as front-line treatments. However, there are toxicity concerns for these drugs, especially asthey are most effective when given at high doses early in disease progression. The ability to administerthese antivirals more safely, particularly in less severely affected individuals, will allow for earliertreatment. In this project, we combine experimental genomic approaches and genetic associationstudies to understand and mitigate toxicity of SARS-CoV-2 antiviral drugs.In Aim 1, we will use state-of-the-art genomic screening to identify human genes that mediate toxicityof SARS-CoV-2 antiviral drugs in liver and intestinal cell lines. In Aim 2, we will examine geneticassociations of remdesivir efficacy and toxicity from ongoing clinical trials. In Aim 3, we will combinethis information to test approved pharmaceuticals or nutrients which are known to target or interact withgenes we identify to determine if any mitigate drug cytotoxicity. We will also determine whether thereare any common genetic or disease conditions for which antiviral dosing may be inadvisable.Altogether, we aim to provide rapid and actionable insight on the toxicity of front-line SARS-CoV-2antiviral drugs.",2020,2021,Brigham And Women'S Hospital,139773,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Adverse events associated with therapeutic administration,2020 +C07067,3U41HG003751-13S1,Rapid and Precise Molecular Pathway Modelling of the SARS-CoV-1 and SARS-CoV-2 Infection Cycle with Human Host Protein and Therapeutic Interactions,"Project Summary: The Reactome Knowledgebase is a widely used and internationally recognized expert-curated, open-sourceresource of a broad array of human biological processes and their disease counterparts, coupled to powerful toolsfor data analysis and display, and integrated with diverse community genomics resources. The work proposedhere will add molecular annotations of the COVID-19 infection process mediated by the SARS-CoV-2coronavirus, interactions between viral components and human host proteins that mediate the severity of viralinfection, and the effects of therapeutics and drug-like compounds on both viral and host proteins. The resultingSARS-CoV-2 pathway annotations will provide a framework for pathway- and network-based data analysis andvisualization, which will be critical for the interpretation of numerous COVID-19 studies now and in the future.In collaboration with a team of community experts in virology, drug design, and infectious disease, we willassemble information in two stages. First, a draft annotation will associate relevant SARS-CoV-1 and SARS-CoV-2 viral and host cell proteins with each stage of the infection process and the host response to it. Theseannotations will be immediately useful for identifying additional relevant interacting proteins, for assessingpossible effects of variation in the host or viral proteins on specific steps of viral infection, and for identifyingpossible drug targets. In the second stage, the SARS-CoV-2 map will be annotated more extensively to fill inmolecular details of each step in these processes and to highlight differences in the processes mediated by SARS-CoV-2 virus and related coronaviruses. This annotation process will continue for the duration of the project toincorporate newly validated molecular details as they are uncovered by the research community.All the data, code and tools developed by this project will be open source and open.",2020,2022,Ontario Institute For Cancer Research,310292,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis",2007 +C07068,3R01DK123733-01S1,Role of Intestinal Barrier Integrity in Modulating the Host Glycome During COVID-19,"PROJECT SUMMARY. Hyper-inflammation and complement activation have been implicated in Coronavirusdisease 2019 (COVID-19) pathogenesis and outcomes; however, the pathophysiological mechanismsunderlying these phenomena remain unknown. SARS-CoV2 infects gut cells, and viral infections in the gutcauses changes in gut structure and breakdown of the epithelial barrier, which can increase permeability to gutmicrobes and microbial products. This microbial translocation has a direct impact on systemic inflammation, butit may also indirectly impact it by modulating circulating glycomes. Recently, it has been shown that viral-infections-mediated alterations to glycans, in particular loss of sialic acid and loss of galactose, on circulatingglycoproteins and antibodies (IgG and IgA) mediate and drive inflammation and complement activation. Gutmicrobial translocation is a potential source of glycomic alterations during viral infections. Translocation ofglycan-degrading enzymes (such as sialidase and galactosidases) released by several members of the gutmicrobiome can efficiently alter circulating glycomes, leading to the exacerbation of inflammation. In ourpreliminary data, we found that levels of several gut bacteria genera correlate with plasma IgG glycosylationduring viral infection. We also found that these pro-inflammatory glycans on IgG correlate with both markers ofmicrobial translocation, as well as with markers of systemic inflammation. These data suggest a link betweenmicrobial dysbiosis, microbial translocation, circulating glycomes, and systemic inflammation during viralinfections. However, the role of circulating glycomes in regulating inflammation during COVID-19 has never beeninvestigated. To fill this knowledge gap, we propose to test the hypothesis that SARS-CoV2 impairs intestinalbarrier integrity leading to translocation of microbial products that alter circulating glycomes, whichimpact COVID-19 pathogenesis and outcomes. In Aim 1, we will test the hypothesis that severe COVID-19 isassociated with disrupted intestinal barrier integrity and dysregulated circulating glycomes. 1.a) We will compareplasma markers of mucosal structural integrity, bacterial translocation, and microbial metabolites of 120 COVID-19 patients (with varying disease outcomes); and 120 controls (matched for age, gender, and ethnicity). 1.b) Wewill compare the glycomic profiles of total plasma, plasma IgG, and plasma IgA of the 120 COVID-19 patientsand controls. 1.c) We will test if levels of plasma markers of mucosal structural integrity and bacterialtranslocation associate with the glycosylation of plasma, plasma IgG, and plasma IgA. In Aim 2, we will test thehypothesis that circulating hyposialylated and agalactosylated glycomic signatures are linked to higherinflammation, higher immune activation, and worse clinical outcomes during COVID-19. This supplement canadvance our knowledge of the microbial and glycomic underpinnings of COVID-19, which can serve as 1) novelbiomarkers for disease risk stratification, disease course, and therapeutic response (to be used immediatelyupon validation); and 2) a foundation to develop innovative therapeutics in the future.",2020,2021,Wistar Institute,456773,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C07069,3R43CA243815-01S2,"An urgently needed low-cost, rapidly deployable platform for simultaneous SARS-CoV-2 viral particle and COVID-19 IgG/IgM detection and quantification","By adapting low-cost technology developed by Nodexus prior to and during the course of the currentNCI Phase I SBIR award, we hereby propose a low-cost, rapidly deployable platform for quantification ofboth SARS-CoV-2 viral particles and anti-SARS-CoV-2 IgG/IgM antibodies simultaneously from saliva bybead-based capture in a simple flow-through assay for low-infrastructure screening utilizing patentedmicrofluidic Node-Pore Sensing (NPS) to urgently address the need for affordable diagnostics andasymptomatic carrier detection to protect at-risk populations including cancer patients andimmunocompromised survivors. The proposed solution further enables rapid deployment to testingcenters and ultimately patient/individual walk-up usability with universal web-based compatibility(including mobile device) for maximum accessibility and adoption for the general public.There is great need for an at-home diagnostic solution like the proposed Nodexus platform because the world iscurrently in the midst of a global pandemic caused by severe acute respiratory syndrome coronavirus 2, orSARS-CoV-2, which emerged from Wuhan, China at the end of 2019. As of May 23, 2020, there are currentlyover >5M cases reported worldwide, and tragically over 338,000 deaths (average mortality rate ~7%, data fromECDC daily tracker). The lack of direct viral particle diagnostic tests currently available has placed an immenseburden on governments around the world to curtail economic and social activities to prevent further communityspread of COVID-19. Recent studies have shown that risk of developing severe events in COVID-19 isstatistically significantly higher in cancer patients. This can present enormous hurdles for engaging with theirsupport system (e.g. family and friend visits) and also lead to fear and safety issues when attending clinical sitesfor checkups, monitoring, and treatment. Nodexus' proposed platform (system and cartridge-based kit) solutionwould offer an affordable, at-home-deployable diagnostic test that would directly detect both the virusand antibodies against COVID-19 in a rapid manner (<20 minutes to result) using saliva samples todiagnose/monitor patients, with particular focus to assist disparately affected populations includingcancer patients and immunocompromised survivors.Saliva was chosen as the optimal diagnostic sample type for a number of reasons. Firstly, saliva samples havea >93% concordance of detection for SARS-CoV-2 as compared to FDA/CDC standard diagnostic test usingnasopharyngeal aspirate (NPA). Secondly, saliva is the easiest sample for patients to self-collect, without thediscomfort or potential bleeding of nasopharyngeal/oropharyngeal swabs, and without the difficulty of sputum toself-collect. Finally, patient self-collecting of saliva significantly has been shown to lower risk of virus spread tohealthcare workers or nearby members of the public compared to more invasive methods which may result inexpectoration or sternutation. Nodexus' proposed platform will ultimately detect viral particles and IgM/IgGantibodies with high sensitivity, specificity, and concordance with NPA qRT-PCR assays.Successful completion of the proposed Aims will significantly contribute to diagnosing COVID infection at theearliest stages (prior to hospitalization becoming needed). Nodexus is well positioned to complete the Aimswithin the urgent timeline based on the previously demonstrated low-cost cartridge production with high marginsusing standard as well as proprietary in-house processes, significant design-for-manufacturing already beingperformed, and because the majority of the proposed platform components have already beendeveloped/integrated into Nodexus' existing products by existing external partners as part of NCI Phase I SBIRaward.",2020,2021,"Nodexus, Inc.",248790,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2019 +C07070,3UM1OD023222-10S1,The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2),"PROJECT SUMMARYIn response to ""NOT-RM-20-015"", we propose an urgent competitive revision to The Jackson LaboratoryKnockout Mouse Phenotyping Project (KOMP2) to develop the next generation of precision mouse models formechanistic discovery of SARS-CoV2 infection and therapeutic discovery of COVID-19 disease treatments.The worldwide response to the COVID-19 pandemic has triggered a surge in demand for animal models tounderstand the underlying biology and pathology of SARS-CoV-2 infection and for the preclinical developmentof novel therapeutic strategies. Several mouse models have recently been reported that respond with varyingdegrees to SARS-CoV-2 infection. However, given the diversity of patient outcomes, any one mouse model ona standard inbred genetic background does not reflect the impact of host genetic context on SARS-CoV-2infection and response to treatment. We therefore propose to create a second-generation mouse modelplatform incorporating diverse genetic backgrounds, to characterize the variation in SARS-CoV-2 infectiondynamics and the development of clinically-relevant disease. The proposed project will rapidly provide theresearch community with an urgently needed resource for linking the variability in COVID-19 disease outcomewith underlying host genetic features, and for developing precision therapies tailored to treat the individualpatient. Our Specific Aims are: 1) To create a panel of genetically diverse transgenic models for SARS-CoV-2infection; 2) To characterize infectivity, phenotypic response, disease outcome, and transcriptomeheterogeneity of these models; and 3) To distribute these models and our outcome data to the scientificcommunity.",2020,2021,Jackson Laboratory,925466,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2011 +C07071,3RM1HG008935-05S1,Center for dynamic RNA epitranscriptomes - Covid 19 Supplement Version 2,"AbstractQuantitative sequencing of SARS-CoV-2 viral RNA modifications and identification of hostmodification enzymes critical to viral RNA replicationA new coronavirus disease (known as COVID-19) has swept 200 countries and was declared apandemic. The causative agent is named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). There is no effective vaccine currently available for SARS-CoV-2. FDA hasapproved two anti-malaria drugs, chloroquine and hydroxychloroquine, for emergency use fortreatment of COVID-19. In addition, remdesivir, a nucleotide analog used for treatment of Ebolavirus disease, is now in clinical trials and clinical use for COVID-19 treatment. Understandingproperties of SARS-CoV-2 and revealing cellular components essential to its infection are criticalto development of effective therapies and vaccines in the near future.SARS-CoV-2 is an RNA virus. Its viral RNAs have been shown to be chemically modified.Previous studies from us and others have revealed crucial roles of viral RNA modifications in viralreplication and immune evasion. Our most recent data indicate that an RNA m5Cmethyltransferase NSUN2 plays a vital role in human coronavirus replication inside host cells. Inthis administrative supplement application we propose to apply quantitative sequencing methodsdeveloped by our CEGS to map N6-methyladenosine (m6A), 5-methylcytosine (m5C),pseudouridine (Ψ), 2'-O-methylation (Nm), N7-methylguanosine (m7G) and N1-methyladenosine(m1A) in SARS-CoV-2 RNA. We will also assign modification enzymes and test their effects onviral infection using established infection models of SARS-CoV-2. We will specifically examinedNSUN2 and its effect on viral RNA m5C methylation, and test known inhibitors for inhibition of viralinfection. We will also examine potential roles of m6A and related modifications in protecting viralRNA from host innate immune responses.",2020,2021,University Of Chicago,388014,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2016 +C07072,1R01AG072301-01,COVID-FIS: A PHASE 2 PLACEBO-CONTROLLED PILOT STUDY IN COVID-19 OF FISETIN TO ALLEVIATE DYSFUNCTION AND EXCESSIVE INFLAMMATORY RESPONSE IN OLDER ADULTS IN NURSING HOMES,"Abstract: Coronavirus-19 (CoV) can cause physical dysfunction, morbidity, and death from hyper-inflammation, acuterespiratory distress syndrome (ARDS), and multi-organ failure, particularly in older or chronically-ill individuals.Across the US, >50% of CoV deaths are in nursing homes and 25-50% of nursing home residents who testpositive for CoV die from these complications. Senescent cells accumulate with age and drive frailty andchronic diseases. These cells can acquire a senescence-associated secretory phenotype (SASP) entailingrelease of many of the same factors as in CoV-induced cytokine storm. We found CoV antigens exacerbate theSASP, SASP factors increase CoV viral entry proteins, and SASP factors impair viral defense mechanisms innon-senescent cells. A coronavirus related to human CoV rapidly kills old but not young mice. We discovereddrugs that selectively eliminate senescent cells, senolytics. They alleviate age-related phenotypes and chronicdisorders in mice and are now in clinical trials, in which they have been found to reduce senescent cell burden,inflammation, and frailty. We found that Fisetin, a natural product flavonoid, has a favorable safety profile in oldmice, monkeys, and elderly humans with multi-morbidity in a trial now underway in which 53 patients havebeen treated. Fisetin decreased cytokine storm and mortality in mice infected with β-coronavirus. An FDA-approved clinical trial of ours has now begun in older hospitalized CoV patients to prevent progression torespiratory failure. Our hypothesis is that targeting senescent cells with Fisetin will delay or preventcomplications of CoV infection in those at great risk: elderly nursing home residents. Aim 1 is to test if Fisetinprevents progression of morbidity in nursing home residents with rt-PCR-proven CoV infection but no, mild, ormoderate symptoms (WHO/NIH Classification) in a double-blind, placebo-controlled, multicenter clinical trialacross nursing homes associated with the NIA-supported Translational Geroscience Network. The primaryoutcome in men and women age >65 (75 Fisetin-treated, 75 placebo) will be prevention of progression, basedon the WHO Ordinal Scale for Clinical Improvement of CoV. Other outcomes will be safety, need forsupplemental oxygen, escalation of care, and death. TGN-based nurses/study coordinators with their own PPEwill minimize impact on thinly-stretched nursing home staff. Fisetin can be provided to the study subjects infoods and drinks. Aim 2 is to test if Fisetin delays, prevents, or alleviates hyper-inflammation and ARDS/multi-organ failure in CoV-infected elderly nursing home residents. When feasible, we will ascertain if Fisetindecreases SASP factors, senescent cell abundance, and viral entry proteins and reduces: progression tosevere or critical CoV, delirium, and hypo-oxygenation. Aim 3 is to test if Fisetin promotes recovery of CoV-infected nursing home residents followed up to 6 months, including antibody response, physical function, andlung fibrosis. This trial will pave the way for more nursing home trials of interventions not only for CoV, butother conditions in the frail elderly. The impact of this clinical trial will extend beyond the current CoV epidemic.",2020,2023,Mayo Clinic Rochester,1917854,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Clinical trials for disease management | Prophylactic use of treatments | Adverse events associated with therapeutic administration",2020 +C07073,3R01CA243486-01A1S1,T-cell intrinsic mechanisms of resistance to PD-1 checkpoint blockade,"Abstract: This Urgent Supplement is addressing the possible effects of cancer therapies, and PD-1 blockade inparticular, on immune responses to COVID-19 infection and vaccination. The primary objective of the parentproposal CA243486 entitled ""T cell intrinsic mechanisms of resistance to PD-1 checkpoint blockade"" is todetermine the function of T cell receptors in the molecular mechanism of resistance to PD-1 checkpointblockade.The COVID-19 pandemic underscores the urgent need for effective vaccines and treatments, especially inimmunocompromised individuals including majority of cancer patients. Previously reported data on animalvaccination against coronaviruses (CoV), including SARS-CoV, demonstrated that parenteral or intramuscularimmunization, which predominantly activates systemic immunity, may be inadequate in prevention of these andother respiratory tract infections. Since respiratory mucosa is a primary target for CoV, it has beendemonstrated that targeted mucosal immunization could be a much more effective strategy as it involvesactivation of all types of adaptive immunity: systemic, mucosal and cellular. It has been shown that resistanceto SARS-CoV infection in mice is primarily driven by cellular immunity represented by the resident memory Tcells. In humans, SARS-CoV-specific memory T cells have been detected in the peripheral blood of SARSpatients six or more years post-infection despite the lack of virus-specific memory B cells. We hypothesize that(1) the long-term protection against CoV including SARS-CoV2 can be achieved by a mucosal vaccine elicitinglong-lasting cellular immunity and (2) checkpoint blockade can elevate the T cell response during COVID-19vaccination. In this supplement to our parent grant we propose to identify SARS-CoV2 specific T cell epitopesin cancer patients and healthy individuals (Aim 1) and utilize the most immunogenic epitopes in engineering ofa recombinant vaccine library (Aim 2). Since short peptide epitopes are poor immunogens, we will utilize anon-toxic cholera toxin B (CTB) protein as a mucosal adjuvant and as a carrier for targeted delivery ofimmunogens to the lung dendritic cells (Aim 2). Next, the vaccine library will be tested for immunogenicityusing mouse models with and without PD-1 blockade to evaluate the effect of checkpoint blockade on T cellactivation during vaccination. The most efficient vaccine prototype will be further validated using a SARS-CoV2mouse model (Aim 3). This project will help to evaluate the role of T cells in immunity to COVID-19 in healthyindividuals and cancer patients, test the efficacy of a novel vaccine using in in vivo mouse model anddetermine the role of PD-1 blockade in T cell response to immunization.",2020,2021,New York University School Of Medicine,169500,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2020 +C07074,3U01DA050442-02S1,Using Implementation Interventions and Peer Recovery Support to Improve Opioid Treatment Outcomes in Community Supervision,"Project SummaryCOVID-19 threatens to exacerbate the ongoing opioid epidemic in the United States, but thepandemic has also provided an opportunity to experiment with changes in how opioid treatmentservices are delivered around the country. The current pandemic has resulted in a flurry ofunprecedented policy measures, and it is crucial to understand the impact that rapid changes inlaw, regulation, and policy are having on individuals with opioid use disorder (OUD), particularlythose involved with the criminal justice system.Deploying law to support, rather than hinder access to treatment requires evidence of whichlegal levers help and which hurt, and a clear mapping of the state of the law in every applicablejurisdiction. Legal epidemiology - the scientific study and deployment of law as a factor in thecause, distribution, and prevention of disease and injury in a population - provides an innovativeframework to understanding the positive, negative, and incidental effects of these policychanges on population health.The research team will use legal epidemiology and policy surveillance methods to collect andsystematically code laws, regulations, executive orders, Medicaid waivers, and other opioid-related policies relevant to the criminal justice system during the COVID-19 pandemic. The legaldata will be published and freely available for download for all users, including JCOIN networkmembers, to evaluate the impact of these evolving legal measures on health outcomes overtime.1",2020,2024,Brown University,184738,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2019 +C07075,3P42ES031009-01S1,Center for Environmental and Health Effects of PFAS,"Project Summary/Abstract This project expands the GenX Exposure Study funded through the NC State Center for Environmental andHealth Effects of PFAS to answer urgent questions related to per-and polyfluoroalkyl substances (PFAS) exposure andtheir impacts on SARS-CoV-2 response. PFAS as a class are associated with immune suppression as evidenced in humansby lower antibody titers to common vaccines in higher exposed individuals. Using the GenX Exposure Study, aprospective study of 1,000 PFAS exposed individuals, we plan to answer two questions: 1) what is the prevalence ofovert disease, symptoms, sequelae, and antibodies in this population? and 2) does PFAS exposure modify response tovirus as measured by antibodies? This study, located in the Cape Fear Region of North Carolina, includes participantsranging in age from 8-86 years with diverse demographic and medical histories. PFAS levels in this study are muchhigher than the national values for PFAS measured; in this population, novel fluoroethers have been measured in serumand represent ~25% of the overall PFAS levels in serum. In this population, we plan to collect two blood samples forSARS-CoV-2 antibody testing, once in the fall of 2020 and again in the summer of 2021. Additionally, we will administera survey related to COVID 19 disease and symptoms at five points in time during this one-year study to capture theongoing disease experience of the cohort. We currently anticipate a prevalence of antibody positive infection of 10%(June 2020); we expect this to increase as the rates of infection are increasing in North Carolina. We will use PFAS valuesmeasured in Fall 2020 to assess the impact of PFAS exposure and SARS-CoV-2 response in cross-sectional analyses; wewill use the same PFAS measures to assess PFAS exposures on these outcomes in a longitudinal fashion for datacollected following PFAS measurement. With 1000 participants, this will be one of the largest studies to date regardingPFAS exposure and immune response as measured by antibodies. Given that PFAS suppress immune function, exposuremay result in worse disease because individuals fail to make sufficient antibodies to the virus, or may result in milderdisease since the so-called ""cytokine storm"" may be mitigated by poorer immune response. Our study will provide thesurvey data combined with antibody data and stored specimens to further explore how PFAS influence COVID. If avaccine becomes available and is adopted during our study, we will shift our focus to vaccine response. We plan to workwith our community partners both local non-governmental organizations and health departments to share results withstudy participants and the community in a timely fashion. This supplement complements the ongoing research at theNC State Superfund Center and allows us to leverage an ongoing epidemiological study to address this important publichealth issue.",2020,2025,North Carolina State University Raleigh,304441,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +C07076,3UM1AI068632-14S2,LOC-IMPAACT Leadership Group Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the US,"PROJECT SUMMARYRemdesivir, the first drug with preliminary evidence of efficacy for treatment of COVID-19, has recently beenawarded Emergency Use Authorization from the FDA for use in hospitalized patients with documented COVID-19. There are no documented pharmacokinetic (PK) and limited safety data available regarding use inpregnancy. The physiological changes associated with pregnancy can have a dramatic impact on drugdisposition, and use of therapeutic agents during pregnancy poses unique safety concerns. The aims of theproposed Phase IV prospective, open label, non-randomized study are to evaluate the PK (Specific Aim 1) andsafety (Specific Aim 2) of remdesivir provided through a compassionate use program or open access protocolin 20 hospitalized pregnant women for treatment of symptoms related to COVID-19, using a well-establishedstudy approach and leveraging the extensive infrastructure of the NIH-sponsored International MaternalPediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and in collaboration with Gilead Sciences. Thestudy will be conducted at multiple experienced IMPAACT-affiliated sites in the US with proven access to thestudy population. Hospitalized pregnant women >18 years of age with COVID-19 scheduled to receiveremdesivir as part of clinical care will be eligible for enrollment if willing and able to provide informed consent orif a legally recognized representative can do so on her behalf. The primary outcome measure will be acomparison of remdesivir PK parameters from study participants (pregnant women) with those in non-pregnantadults. The primary PK endpoints are remdesivir and its major metabolite, GS-441524, AUC0-24h at Day 1, andGS-441524 AUCtau after last dose. Intensive and sparse sampling remdesivir concentrations will be used in apopulation PK analysis to assess the impact of covariates such as stage of pregnancy and severity of COVID-19 disease on remdesivir PK parameters. Plasma remdesivir and GS-441524 concentrations will be quantifiedin the laboratory being used for ongoing Gilead-supported studies of remdesivir in non-pregnant adults,ensuring comparability. At entry and after the last dose, safety monitoring will include liver and renal functiontests and complete blood count (if not obtained within 24 hours for clinical care) and medical record Abstract: Ionfor other laboratory test results and clinical events. Medical record Abstract: Ion for laboratory test results andclinical events will also be performed at 4 weeks postdosing and after labor and delivery. The proposed studywill provide urgently needed pregnancy-specific clinical pharmacology data that will ensure that remdesivir canbe used safely and effectively in pregnant women as rapidly as possible. This research could also serve as amodel to rapidly provide pregnancy PK and safety data for other COVID- therapeutics as they becomeavailable.",2020,2020,Johns Hopkins University,942554,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C07077,3R01HL141237-02S1,IFN responses and SARS-CoV-2 Receptor ACE2 Expression in the airway epithelium of young children with Down Syndrome,"ABSTRACTDown syndrome (DS), also known as trisomy 21, is the most common chromosomal abnormality among live-born infants. DS is associated with a disproportionate high risk for severe viral respiratory infections, a topcause of mortality in this vulnerable population. Nonetheless, the risk of DS patients to develop severe SARS-CoV-2 infections during the COVID-19 pandemic has been remarkably understudied. A major concern in DSindividuals the risk to develop hyper-inflammatory responses manifested as cytokine storm and/or multisysteminflammatory syndrome in children. Indeed, people with DS exhibit hyper-activation of interferon (IFN) signalingbecause they have three copies of the chromosome 21, which encodes four of the six IFN receptors.Importantly, our team and others recently identified that IFNs are strong inducers of the angiotensin-convertingenzyme 2 (ACE2), the cell entry receptor of SARS-CoV-2 in the human airway epithelium. The novel findingthat SARS-CoV-2 may tap into the host IFN-driven airway epithelial antiviral response to enhance its infectivityrepresents a paradigm shift for the pathobiology of COVID19, particularly in individuals with DS. The overallgoal of this application is to investigate, for the first time, the airway epithelial IFN-driven antiviral and pro-inflammatory responses in young children with DS. Our NIH-funded laboratory (R01HL141237) has theexpertise to study the immunobiology of the airway epithelial cell (AEC) of young children, the age group withthe highest risk for severe viral respiratory infections. Our central hypothesis is that the airway epitheliumof DS children exhibits a dysregulated antiviral molecular program leading to enhanced production ofpro-inflammatory cytokines and IFNs (Aim 1); and heightened responsiveness to IFNs leading tooverexpression of ACE2 and increased susceptibility to SARS-CoV-2 infection (Aim 2). Defining the keyinnate cytokines/chemokines and the precise molecular pathways dysregulated in the AEC of DS individualspromises a unique opportunity to discover novel targets to treat severe viral respiratory infections, includingSARS-CoV-2. This new knowledge may have long-lasting impact for people with DS by identifying potentiallynovel approaches to prevent severe respiratory infections caused by SARS-CoV-2 and other viruses (e.g.RSV) in children and adults with DS.",2020,2023,Children'S Research Institute,489740,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2020 +C07078,3R01DK093770-09S1,Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcomes,"Abstract: The incidence of AKI is 20-30% in patients hospitalized with COVID-19 in the United States, andis over 40% in patients admitted to the ICU. Moreover, the mortality rate in patients thatexperience AKI in the setting of COVID-19 is approximately 2- to 10-fold higher than patientswithout AKI. The pathogenesis of AKI in COVID-19 infection remains unclear and it is not knownif the injury to the tubule is direct result of the virus infection or if it is secondary to other organcomplications. Availability of urine, blood and tissue samples early in the course of infection willprovide important pathogenic insights for therapeutic and clinical management.The Translational Research investigating Biomarker Endpoints (TRIBE)-AKI consortium has along-standing history of conducting multidisciplinary epidemiologic and translational researchstudies in the setting of AKI. They have experience with long term follow-up of hospitalizedpatients, tissue and sample handling as well as analytic considerations. We propose aprospective observational study of the clinical and biologic predictors of major adverse kidneyevents and death (MAKE-D) in COVID-19, including the following: severity of AKI (stages 1, 2,3 and requiring dialysis), mortality, and non-recovery of AKI and transition to chronic kidneydisease.We will examine consecutive patients hospitalized with COVID-19 at three premier academichospitals participating in the TRIBE consortium: Johns Hopkins Medicine, Mount Sinai Hospitaland Yale-New Haven Hospital. We assess the incidence, severity, and clinical predictors ofMAKE-D during hospitalization and at 90 days following discharge. We will investigate thepossible role of injury, inflammation and repair mechanisms through biomarkers in the bloodand urine in serial samples collected from patients during hospitalization. We will also performadvanced evaluation of kidney biopsies using single cell RNA sequencing to identify possiblemechanistic disease pathways, which may lead to novel therapeutic targets.Combating this pandemic will require a multidisciplinary approach from the medical researchcommunity, including rigorously conducted epidemiologic studies that include granular patient-level data and translational research studies to understand the pathogenesis of COVID-associated kidney disease.",2020,2021,Johns Hopkins University,718018,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2012 +C07079,3U01DK073975-15S2,Effects of COVID-19 in Patients with Gastroparesis: A GpCRC Supplement,"ABSTRACT:Coronavirus Disease 2019 (COVID-19), a disease caused by infection with Severe Acute RespiratorySyndrome Coronavirus 2 (SARS-CoV-2), commonly presents with symptoms including fever, cough, andshortness of breath. Some patients have tested positive for SARS-CoV-2 after developing gastrointestinal(GI) symptoms either solely or in conjunction with pulmonary symptoms. This may be due to SARS-CoV-2infection of the GI tract or a systemic effect from the respiratory viral infection. In patients with chronic GIillnesses, such as gastroparesis, COVID-19 may present as a flare of their underlying GI condition asviruses have historically been implicated in exacerbations of chronic GI disorders, including gastroparesis.Some patients with no underlying GI conditions have been diagnosed with COVID-19 after presentingpredominantly with nausea, vomiting and diarrhea. They may be at risk for developing post-viralgastroparesis, which is an important and poorly understood potential chronic inflammation-based cause of""idiopathic gastroparesis"". The NIH Gastroparesis Clinical Research Consortium (GpCRC), consisting of sixclinical centers and its Scientific and Data Research Center (SDRC), is following the largest number ofpatients with gastroparesis and dyspepsia symptoms. These patients are well phenotyped. In addition todetailed physiological phenotyping, every 6 months we obtain detailed questionnaires, and store plasmaand serum. The overall goals of this supplemental grant are to determine if COVID-19 affects clinicalcourse of patients with gastroparesis and whether COVID-19 is associated with development ofpost-infection gastroparesis and/or functional dyspepsia. We will accomplish these goals byundertaking the following three specific aims involving patients in our gastroparesis registry. Aim 1.Determine the prevalence of SARS-CoV-2 infection in patients with confirmed gastroparesis to help assessif SARS-CoV-2 infection disproportionately affects patients with gastroparesis compared to generalcommunity population in same geographic location. Aim 2: Determine if COVID-19 affects the clinicalcourse of patients with gastroparesis by causing more flares than usual, increasing the severity ofgastroparesis symptoms, and decreasing gastric emptying. Aim 3: Characterize patients developing newonset gastroparesis and functional dyspepsia after COVID-19 in patients. Currently, the GpCRC is the onlylarge, NIH-funded registry of patients with chronic GI symptoms from gastric dysmotility (gastroparesis). TheGI epithelial involvement with SARS-CoV-2 as well as the existing rationale that such infections can led tochronic gut dysfunction, makes GpCRC ideally poised to conduct this research. This research project will beaccomplished within 1 year timeline to produce impactful clinical data to understand GI implications ofSARS-CoV-2 infection. This proposed study will be implemented at all six clinical sites of the GpCRC withSDRC for coordination and Mayo Clinic core of the GpCRC will be used for SARS-CoV-2 serology testing.",2020,2021,Temple Univ Of The Commonwealth,352133,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2006 +C07081,3R01CA229174-02S1,Developing newly combined therapeutic strategies for mature B cell lymphoma,"Cancer patients inflicted with COVID-19 are at 3.5 times the risk of requiring mechanical ventilation or ICU admission, compared to the general population. Infection of SARS-CoV-2, the causative agent of COVID-19, elicits both T and B cell responses against the virus and the successful coordination of these systems working in concert would normally lead to the control of the viral infection. However, if the immune system is compromised or defective, SARS-CoV-2 may undergo unchecked viral replication triggering cytokine storm, multiple organ failure and ultimately lethality. Conventional wisdom would suggest that fatality rate should be higher in COVID-19 infected cancer patients. While many cancer therapeutics such as chemotherapies preferentially target cancer cells, they also hurt normal cells to a degree, particularly the very cells that are involved in immune responses to infectious agents. Consequently, chemotherapies may weaken the host defense system to allow viral spreading. Other cancer treatments such as immunotherapies or CAR-T, which seek to enhance immune responses of patients to tumors, could be a double-edged sword as these treatments may also enhance the cytokine storm responses. The high mortality rate of cancer patients infected with SARS-CoV-2 begs the question whether vaccination should be prioritized. However, the effectiveness of vaccine in patients with cancer and the presence of tumors with or without anti-PD1 treatment on the development of SARS-CoV-2 immunity remains largely unknown. The goal of this administrative supplement is to investigate the effects of tumors or anti-PD-1 treatment on T and B cell responses against SARS-CoV-2 antigen in a unique syngeneic mouse tumor model we developed. We hypothesize that the presence of tumor compromises mounting of an adequate immune response to viral antigens and impedes production of neutralizing antibodies. Anti-PD1 treatment may enhance SARS-CoV-2 immunity. Two aims are proposed. In SA1, we will characterize T and B cell immune responses to SARS-CoV-2 in wild type (WT) and tumor-bearing mice. In SA2, we will determine the effect of anti-PD1 treatment on T and B cell immune responses to SARSCoV-2 in WT or tumor-bearing mice. The result may provide novel insights into the observed high mortality rate of SARS-CoV-2 inflicted cancer patients, and inform the vaccination strategy for cancer patients.",2020,2021,University Of Colorado Denver,154751,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2019 +C07082,1R01AI157155-01,Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2,"Project Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virusthat was first isolated in Wuhan China in December, 2019. SARS-CoV-2 is the cause of coronavirus disease2019 (COVID-19), which is now a pandemic and has caused more than 1.3 million confirmed cases and 72,000deaths, with an estimated case fatality rate of 4%, with substantially higher death rates (~15%) in the elderly orimmunocompromised. Virtually all countries and territories have reported cases, with major epidemics in China,Italy, Spain, France, Germany, Iran, and the United States. SARS-CoV-2 is thought to be of zoonotic origin, mostlikely bats, and is about 75% identical to the original SARS-CoV. Most cases are spread by direct human-to-human transmission, with community transmission in asymptomatic individuals described. Currently, nocountermeasures are licensed for human use. The development, characterization, and ultimately deployment ofan antibody-based treatment against SARS-CoV-2 could prevent substantial morbidity and mortality, andpossibly mitigate its epidemic spread. This interactive multi-PI proposal leverages complementary expertise inthe Diamond, Crowe, and Baric laboratories to rapidly develop highly neutralizing and therapeutic humanmonoclonal antibodies (mAbs) against SARS-CoV-2 for immediate use in humans. To achieve this goal, we willgenerate and interrogate human mAbs against SARS-CoV-2 that are obtained from multiple convalescentsubjects. We will identify potently neutralizing mAbs and optimize them for affinity by selecting naturally occurringsomatic variants identified by repertoire sequencing and sibling analysis and Fc effector functions. Protectiveactivity of top candidate coronavirus mAbs will be tested in newly-generated and optimized mouse models ofSARS-CoV-2 infection, including those expressing human ACE2 receptors (hACE2). To define correlates ofprotection, we will use chimeric viruses, shotgun mutagenesis, and neutralization escape to identify the epitopesof our most protective mAbs. Our team has extensive experience in the generation, characterization andoptimization of antibodies, CoV biology, and animal models of disease and protection. A therapy composed ofone to three highly neutralizing mAbs may provide an immediate countermeasure against the pandemic spreadof SARS-CoV-2 and help establish correlates of structural and functional humoral protection that ultimatelyinform vaccine efforts.",2020,2025,Washington University,1193309,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C07083,3U2CES030167-03S2,Genetics and quantum chemistry as tools for unknown metabolite identification,"Project Summary/Abstract: The SARS-CoV-2 virus and resulting COVID-19 pandemic has created the biggest global health crisis in ourlifetime. We have assembled a team of investigators with expertise in vaccine development, environmentalexposures, immunology, metabolomics, lipidomics, and modeling to discover metabolic predictive biomarkers(MPBs) of infection in ferrets. We will use ferrets, because they have already been shown to be an effectiveanimal model for human COVID-19 disease, and they are currently being used for vaccine development.Our study builds upon an NIH funded co-infection study in which ferrets will be infected with 4 different commonrespiratory viruses before infection by SARS-CoV-2. That study will determine the severity of infections andimmune responses, but it did not include metabolomics measurements. The hypothesis of the co-infections isthat the severity of SARS-CoV-2 infection will be attenuated with co-infection by another virus. We will be addinga group of ferrets that will be exposed to per- and polyfluoroalkyl substances (PFAS) prior to infection by SARS-CoV-2. PFAS have been shown to suppress the immune system in mice, and a limited number of studies havedemonstrated associations between severity of virus infection and levels of PFAS. PFAS bioaccumulate intissues and are common chemicals used in many everyday items such as plastic bottles and non-stick cookingpans, so this common environmental exposure could be an important variable in COVID-19 symptoms. Theferret model provides an ideal way to study the effect of PFAS on SARS-CoV-2 infection progression andoutcomes. For each group in the study (co-infection, PFAS, or control), 15 serum samples will be collected fromeach animal (n=6 for each group) over about 1 month, with SARS-CoV-2 infection occurring at the midpoint ofthe sampling. Thus, we will be able to derive detailed time-course measurements of metabolites and lipids andassociate these signals with phenotypic outcomes.We have 3 specific aims: 1) Conduct the co-infection and PFAS exposure studies in BSL-3 containment andcollect immunological and infectivity data. Serum samples will be collected and inactivated by a biosafety-approved protocol. 2) Measure metabolites and lipids using non-targeted LC-MS and NMR. NMR is faster andless expensive and will be used to prioritize samples for LC-MS. Background PFAS signals from animal housingequipment will be determined. 3) Model the metabolites and lipids with phenotypic outcomes. We will also modelthe influence of PFAS exposure on the lipidome to better understand the molecular mechanisms of PFASimmunotoxicity.We have also started a Slack workspace for communication between different groups around the worldworking on COVID-19 metabolomics. This workspace provides for sharing of protocols and data, posting thelatest research in this area, as well as a forum for questions and answers. All data generated from our study will be shared publicly as soon as it passes our system suitability tests.",2020,2022,University Of Georgia,351409,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2018 +C07084,3R01AI104870-07S1,Distinct contributions of CCR4 versus CCR7 to thymocyte localization and central tolerance,"PROJECT ABSTRACTSome COVID-19 patients fare well, experiencing asymptomatic or mild disease, while up to 20% of patients havesevere symptoms that can be fatal. Recent studies reveal elevated inflammatory cytokines and a reducednumber of T cells in patients with severe disease, indicating that variation in immune responses may underliedifferences in disease outcomes. However, features of protective versus pathologic immune responses to SARS-CoV-2 are not well understood. Furthermore, children tend to experience milder symptoms, while elderlyindividuals are more susceptible to severe disease, but it is not known if this is a function of age-associateddifferences in immune responses. In Aim 1, we propose to carry out paired single-cell transcriptomics,proteomics, and TCR repertoire sequencing of longitudinal blood samples from COVID-19 patients of differentages and disease severities in order to comprehensively profile the trajectory of immune responses to SARS-CoV-2 and identify candidate immune signatures that correlate with disease severity and age. Candidatesignatures will be tested and refined in a larger patient cohort. Current vaccine efforts are focused on elicitingneutralizing antibodies against SARS-CoV-2. CD4+ T-cell responses are required to activate B cells to produceneutralizing antibodies and to support differentiation of CD8+ T cells, which can promote viral clearance andmaintain immunologic memory. However, viral epitopes that activate protective T-cell responses remainunknown. In Aim 2, we will activate T cells from the longitudinal patient samples used for single-cell profiling inAim 1 with ""megapools"" of overlapping peptides, spanning individual SARS-CoV-2 antigens. Activated T cellswill be subjected to single-cell multi-omics analysis, allowing us to identify TCR sequences of clones that respondto each viral protein. Retrospective analysis of datasets from Aim 1 will enable us to follow the natural progressionof these individual clones to evaluate frequencies and differentiation over the course of disease. Using thesedata, we will determine which viral antigens activate specific T-cell clones during effector and memory phasesthat correlate with favorable outcomes at each age, informing vaccine design. The increased incidence inautoimmune syndromes, such as the Kawasaki-like disease reported in pediatric patients, suggests that SARS-CoV-2 may induce autoimmunity; conversely, patients with autoimmune syndromes may be more susceptible tosevere disease due to immune dysregulation. In Aim 3, we will explore both possibilities. Specifically, we willretrospectively determine if autoimmunity predisposes patients to severe disease and if autoimmune patientshave more inflammatory T cell responses to SARS-CoV-2 antigens. We will also evaluate whether autoantigenswith high sequence similarity to SARS-CoV-2 peptides activate a higher frequency of T cells in COVID-19patients versus uninfected controls, and we will determine if COVID-19 patients develop autoantibodies. Thesestudies will identify specific immune correlates of disease severity at each age to stratify patients into risk groups,inform vaccine design, and test links between autoimmunity and COVID-19 for informed clinical care.",2020,2022,"University Of Texas, Austin",963188,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C07085,3U01AG054580-04S3,Toward Next Generation Data on Health and Life Changes at Older Ages: Administrative Supplement to track the effects of the COVID-19 pandemic on American families,"Abstract: This administrative supplement proposes to continue a high-frequency longitudinal survey ofAmericans' experiences and behavior during the COVID-19 pandemic. The longitudinal surveywas started on March 10. The survey will be conducted of respondents to the UnderstandingAmerica Study (UAS), a probability-based panel of 8,500 adults representing the entire UnitedStates. Housed in the Center for Economic and Social Research, at the University of SouthernCalifornia, the UAS employs an 'Internet Panel,' in which respondents answer surveys on acomputer, tablet, or smart phone, wherever they are and whenever they wish to participate.Respondents are recruited through Address Based Sampling and receive a tablet and broadbandInternet subscription if needed, thus facilitating coverage of the entire adult population 18 andover in the U.S. The set-up allows for an immediate and efficient transmission of data, which arequickly made publicly available through its online platformWe will invite 7,000 UAS respondents to answer bi-weekly surveys (500 every day) through therest of the year. We will report moving weekly averages that will be updated every night byincorporating the newest batch of responses. Thus, results will be based on a rotating sample ofresponses. Importantly, since the same respondents will be answering every other week, we willbe able to track changes with much more accuracy than when one would draw new samplesevery week. Updated results will be posted on the UAS web-site every night.A questionnaire will measure (a) perceptions of coronavirus risk, (b) individual preventionbehaviors, including use of a face mask, hand hygiene, avoidance of health facilities, and otherforms of social distancing, (c) consumption of coronavirus information from various sources, (d)effects on the household's financial situation and their consequences for physical and mentalhealth, health care, psychological distress and substance use, and (e) coping behavior ofhouseholds.",2020,2022,University Of Southern California,3780279,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2017 +C07086,3R01ES026170-05S1,The effect of a housing mobility program on environmental exposures and asthma morbidity among low-income minority children,"Abstract: Minority populations in the U.S. are much more likely to be infected with the novel coronavirus SARS-CoV2and experience severe COVID-19 disease. In this proposal, we leverage our existing cohort of low-incomechildren with asthma who participate in a housing mobility program to characterize rates of SARS-CoV2infection and disease among participating children and their household members, to explore the relationshipbetween indoor allergen and pollutant exposures, including second-hand smoke and SARS-CoV2 infection anddisease, and to assess the impact of pandemic conditions on indoor exposures relevant to asthma among thispopulation. This cohort presents a unique opportunity to study SARS-CoV2 within a cohort of children with wellphenotyped asthma and well-characterized indoor exposures.",2020,2021,Johns Hopkins University,295118,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Disease pathogenesis | Indirect health impacts,2020 +C07087,3R01DK123749-01S1,"Determination of mucosal immune responses to, and infection of the gastrointestinal tract by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)","PROJECT SUMMARYIn approximately 6 months, the Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe acuterespiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in >6 million cases and led to >350K deathsworldwide, with over 100K of these deaths in the USA alone. Although the major pathologies leading to thesedeaths are cardiovascular and pulmonary in nature, COVID-19 is a multi-system disease and gastrointestinal(GI) symptoms are frequently reported. While animal studies and in-vitro experiments demonstrate thatenterocytes can be infected by SARS-CoV-2, analyses of the GI tract in humans have been limited to viralRNA detection in feces or suggestions of enteric inflammation as measured by elevated levels of fecalcalprotectin in a subset of patients. Being at the forefront of COVID-19 cases in New York City, we haverecruited a cohort of >60 individuals. With a strong collaborative infra-structure supported by the parent R01grant focusing on host-viral (HIV-1 associated) interactions in the GI tract, we are well-poised for detailedanalyses of intestinal tissues in COVID-19 patients. Specifically, as evidenced in the submitted application, wehave already generated a strong body of data, demonstrating for the first time, human enterocyte infection bySARS-CoV-2 that is in some cases associated with evidence of intestinal inflammation as measured by fecalcalprotectin and numerous fecal cytokines. We are in the process of determining how these inflammatoryresponses modulate SARS-CoV-2 specific immune responses as measured by fecal IgA. The supplementaryfunds as requested will allow us to continue with the analyses of specimens that are already banked and willenable further recruitment of patients with active and convalescent COVID-19 disease. With the proposedstudies, we aim to a) further characterize infection of GI tissues; b) determine viral persistence in the gut duringconvalescence; and c) determine the generation and evolution of inflammatory and antigen-specific mucosalimmune responses. Altogether, through further development and analyses of this unique cohort, we aim toprovide important insights into the role played by the GI tract in COVID-19 pathogenesis and transmission.",2020,2021,Icahn School Of Medicine At Mount Sinai,787826,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C07088,3R01CA114567-12S1,Testing a cancer patient-specific SARS-CoV-2 vaccine in chemotherapy- and radiation-treated pediatric brain tumor mouse models,"We are proposing work that will address the fundamental question of whether or not the SARS-CoV-2 Spike protein, the basis of many leading COVID19 vaccine approaches, is sufficiently antigenic to elicit neutralizing antibody responses in pediatric patients undergoing chemotherapy. We will immunize control mice and mice undergoing relevant regimens of chemotherapy with a SARS-CoV-2 Spike protein construct found in many leading vaccine approaches, as well as a SARS-CoV-2 Spike protein stabilized with a novel trimeric computationally designed circular tandem repeat protein (a 'cTRP' or 'toroid'). We believe that the toroid scaffold will better stabilize the trimeric Spike protein in the ideal prefusion confirmation necessary for eliciting neutralizing antibody responses, as well as provide a necessary boost of immunogenicity through the in-silico sequence and repetitive nature of the cTRP scaffold. We will assess the antigenicity of the two constructs by examining the ability of serum isolated from the immunized cohort to neutralize a SARS-CoV-2 pseudo virus in a well-established infectivity assay. The results will inform the likelihood of vaccine effectiveness in patients undergoing chemotherapy and potentially provide an alternative vaccine candidate specifically designed to safely elicit antibody mediated protection in the immunocompromised.",2020,2023,Fred Hutchinson Cancer Research Center,176000,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity",2005 +C07089,3R01DK109720-04S1,The KIDCOV Study: Assessment of Kidney Injury and Associated Risk Factors for SARS-CoV-2,"ABSTRACTFrom early studies and published reports indicate kidney injury is one of the manifestations of COVID-19. Thehuman kidney is a direct target of the virus, as the angiotensin-converting enzyme 2 (ACE2), a putative receptorfor SARS-CoV-2, is highly expressed in the kidney tubules. As direct evidence of the virus localizing to the kidney,SARS-CoV-2 viral RNA can be observed in urine and kidney tissue from patients with COVID-19. Kidney injurycan result in acute kidney injury in ~60% of hospitalized patients. The incidence, prevalence and risk factorsof kidney injury in patients with mild/ asymptomatic out-patient COVID-19 disease is as yet unknown. Thisforms a large cohort of SARS-CoV-2 infected patients in the community world-wide.We propose in this supplement to the parent RO1 that examines suPAR and other circulating factors in FSGSdisease, that urinary suPAR and other urine biomarkers that comprise a novel highly sensitive and quantitativeassay (the Kidney Injury Test), can provide an assessment of the incidence and prevalence of kidney damagein COVID-19 by home-based urine testing, independent of any blood test requirement. In this study, weare hypothesizing that risk of kidney injury in COVID-19 disease, also varies by race/ethnicity and otherdemographic factors, is exacerbated by COVID-19 infection, and is more severe in those with a history of or riskfactors of kidney disease. We have made careful selection of 7 large academic medical center study sites, in3 states, to address these questions in the KIDCOV prospective, multi-center study.To test the hypothesis and to achieve the aim of the KIDCOV project, we will perform the study in three stages:.In the first stage, we will enroll outpatient COVID-19 positive patients. COVID-19 positive patients will be enrolledfrom academic medical centers in California (University of California, 5 campuses), Michigan (University ofMichigan) and Illinois (Rush University). Prospective matched cohorts of COVID positive and COVID negativeindividuals, balanced by race/ethnicity, will be identified through EMRs and contacted by phone within 2 weeks ofscreening to provide consent and complete a baseline questionnaire.In the second stage, over the following 12 months, urine samples will be collected and shipped for the assessmentof specific urinary markers at UCSF central lab (cell-free DNA (cfDNA), methylation of cell-free DNA (mcf-DNA),clusterin, CXCL10, protein and creatinine) to compute a validated Kidney Injury Test (KIT)-Score for sensitiveassessment of early kidney damage. Acute kidney injury markers, NGAL, KIM-1 and suPAR will also bequantitated in urine as correlates of kidney damage with the KIT-Score.In the final phase, data analysis will be done to compare the proportion of patients with kidney injury between theCOVID-19 positive and COVID-19 negative groups and identify groups at higher risk for kidney injury, with primaryfocus on COVID19 status, history/risk factors of prior kidney disease, and geographic, demographic and ethnicvariation.",2020,2022,University Of California-San Francisco,459623,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2017 +C07090,3R01CA237401-01A1S2,Investigating the effect of SARS-CoV-2 infection on metabolic reprogramming in lung cancer,"PROJECT SUMMARY/Abstract: Metabolic reprogramming with aerobic glycolysis is a hallmark of cancer. We have previously shown thatglucose transporter expression evolves during lung carcinogenesis, with pre-malignant and early-stage lesionsrelying on sodium-glucose transporter 2 (SGLT2) and advanced cancers switching to GLUT1-mediateddiffusion. Our parent R01 project is focused on the hypothesis that heterogeneity of glucose transport reflectsheterogeneous metabolic and biological phenotypes: SGLT2 is associated with mitochondrial metabolism andslow proliferation in early lesions, GLUT1 with glycolytic metabolism and fast growth in advanced, poorlydifferentiated cancers. Early lesions of the lung adenocarcinoma spectrum are slow growing and can takeyears to progress, or may never progress, to invasive cancer. This indolent behavior correlates with absence ofGLUT1 and expression of SGLT2. The molecular events that drive the switch from SGLT2-positive indolentlesions to GLUT1-positive aggressive cancers are unknown; we are testing the hypothesis that metabolicreprogramming and GLUT1 upregulation play a driving role in this progression.Pulmonary viral infections cause atypical pneumonia, characterized by interstitial inflammation and lowmetabolic activity as measured by positron emission tomography with the tracer FDG, which detects GLUT1activity. However, intensely FDG-avid lesions have been observed incidentally in asymptomatic patients whothen resulted positive for SARS-CoV-2 infection. The absence of systemic or local symptoms suggests that thehigh FDG uptake is not due in these cases to massive inflammatory responses, but to increased glucoseuptake by alveolar epithelial cells infected by SARS-CoV-2. Viral infections can cause metabolicreprogramming in the host epithelial cells similar to the Warburg effect described for cancer, and thisreprogramming is required for viral replication.Here, we will investigate in vitro and in vivo the hypotheses that 1) SARS-CoV-2 infection in alveolar epithelialcells induces metabolic reprogramming with increased glycolysis and intensely positive FDG uptake; 2) if thismetabolic reprogramming is induced in pre-malignant lesions of the lung adenocarcinoma spectrum, the virus-induced switch from SGLT2-driven mitochondrial metabolism to GLUT1-associated glycolysis accelerates theprogression of early-stage, indolent lesions to aggressive, poorly differentiated and invasive cancers.",2020,2021,University of California-Los Angeles,140227,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2020 +C07091,3U2CCA233238-01S1,The Lung PCA: A Multi-Dimensional Atlas of Pulmonary Premalignancy,"In this proposal, that enhances ongoing Lung PCA studies, we propose aims to examine the protein localization, cell type specific expression, and biological pathways up-regulated with key SARS-CoV-2 viral entry genes across the various stages of lung cancer development. We will compare these results with protein expression of key SARS-CoV-2 viral entry genes as well as immune, epithelial, and endothelial cell proteins in lung tissue from patients that died from COVID-19, and from lung tissue sampled pre- and post-COVID-19 disease. Spatially characterizing the epithelium and stromal microenvironment and expression of key SARS-CoV-2 entry genes during the development of lung cancer in the central airway and the alveoli may identify potential ways to improve clinical management of this high-risk patient population and improve COVID-19 outcomes",2020,2023,Boston University Medical Campus,159890,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2018 +C07092,3UG1CA189828-07S3,COVID-19 RELated Barriers to Trial Participation Equity (CO-RELaTE),"The broad long-term objective is to reduce cancer health disparities in women of color (WOC) through increased participation in clinical trials. Cost concerns are a known barrier to trial participation that disproportionately affect WOC. The personal and state- and local-level economic consequences of COVID-19 may disproportionately affect WOC, intensifying financial hardship and widening the gap in trial participation between WOC and non-WOC. The specific aims of this study are to compare 1) the proportion of WOC who experience COVID-related financial hardship (income/employment/insurance loss) vs non-WOC, in a population of women who decline participation in Tomosynthesis Mammographic Imaging Screening Trial (TMIST), a randomized controlled trial of digital mammography (DM) vs tomosynthesis (TM) to evaluate stage shift in screen-detected cancers; 2) the effects of other sociodemographics, and state- or local-level COVID-19 factors on TMIST participation, between WOC and non-WOC. The proposed study is an observational cohort of women who decline to participate in TMIST. In Aim 1, decliners will be surveyed regarding COVID-19 related financial hardship and distress. Among decliners, the proportion of WOC vs non-WOC who experience COVID-related financial hardship will be compared, accounting for patient-, practice-, local- and state-level COVIDrelated factors. In Aim 2, the observational cohort of decliners will be combined with an observational cohort of agree-ers during the same time period. The effects of sociodemographics, and state- and local-level COVID-19 on trial participation will be compared between WOC vs non-WOC. The COVID-19 specific survey in Aim 1 will not be administered to agree-ers and patient-level COVID-19 financial hardship and distress will not be incorporated into AIM 2 analyses.",2020,2025,Ecog-Acrin Medical Research Foundation,118727,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2014 +C07093,3R21CA229069-02S1,SNAP-X: Development of a Mutagenesis Strategy and High Density Protein Array to Comprehensively Display Protein Variants,"This application is being submitted as an Administrative Supplement in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-042. Study of highly infectious diseases, especially those caused by viruses, poses unique biosafety challenges to the scientific research community. Rather than lose the insights this research can provide, common workarounds exist to reduce the risk of studying infectious virus by examining the proteins encoded by the virus in the absence of a fully infectious particle. This approach has been employed for many other viruses and has been proven effective in obtaining valuable data. However, viruses like SARS-CoV-2 mutate leading to many different strains and sequence variations, and it can be difficult to predict which mutations alter virus transmission, infection symptoms, or vaccine / treatment efficacy. Given that cancer patients constitute an at-risk population for Covid-19, this is even more complicated in the context of how cancer cells affect virus infection or how the virus affects cancer progression. Methods to examine virus protein mutations in a high throughput, systematic, and comprehensive (i.e. every mutation) manner are completely lacking. To help address this challenge, we propose to harness our innovative high throughput mutagenesis strategy to comprehensively generate plasmids of every possible point mutation of the SARS-CoV-2 S ""spike"" protein as the key viral recognition protein of the human entry receptor, towards accelerating functional studies and vaccine development. The resulting plasmid set is especially useful for functional assays to identify critical S protein variants, which is a vital area of current Covid-19 research. The S protein mutant plasmid set will be validated by expression of the variant plasmids in human cells and determination of which variants bind to different commercially available SARS-CoV-2 S protein antibodies. These results will be confirmed by immunofluorescence staining. While we envision these variants being employed by the cancer research community in their model systems, they can be used equally effectively by the SARS-CoV-2 research community in general. The proposed method significantly improves on random mutagenesis by error-prone PCR by avoiding its substantial mutational bias and ensuring exactly one mutation per plasmid for streamlined analysis. This strategy will be confirmed by next generation sequencing (NGS), comparing against error-prone PCR. Following successful validation assays for the S protein variant pool, we will generate mutant plasmid sets for three additional key proteins encoded by the SARS-CoV-2 genome. This Administrative Supplement is within the scope of our parent IMAT award, which is a technology development R21 mechanism, to generate all mutants of three key oncoproteins and link the expressed protein variants back to specific feature locations on a microarray. Upon successful completion of this Administrative Supplement, we intend to prepare a SBIR Phase I to sort each individual SARS-CoV-2 mutant plasmid into distinct wells of multiwell plates for additional availability to the Covid-19 research community.",2020,2021,"Proteovista, Llc",129050,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2019 +C07094,3R01AG056587-03S1,Optimizing Self-Monitoring Smartphone App to Promote Adherence to COVID-19 Preventative Behaviors in African Americans,"PROJECT Summary: As the United States faces a rise in known COVID-19 cases, an innovative strategy that expands communityadherence to CDC recommended preventative behaviors (e.g., hand washing and social distancing) is crucialto controlling the COVID-19 pandemic and saving lives. Given the vaccine and specific antiviral treatment forCOVID-19 will take months or years to finalize, preventive behaviors remain the most effective strategy thusfar.Adapted from the ecological momentary assessment (EMA) used in the parent R01 for smartphones, we planto develop a self-monitoring EMA (SM-EMA) intervention to collect real-time behavior data and promoteadherence to COVID-19 preventative behaviors. The central hypothesis of this study is that tailored-feedbackmessages via SM-EMA, a theory-based intervention, will improve knowledge and self-efficacy, which willconsequently lead to self-guided implementation of CDC-recommended preventative behaviors.The proposed research addresses the ongoing COVID-19 pandemic, focusing on African Americans who are aparticularly vulnerable population. It is innovative in its large-scale testing of a novel SM-EMA to reinforcepreventive behaviors and its examination of the sustainability of engagement. The mobile-enabled SM-EMAintervention will involve tapering pop-up messages, behavioral self-monitoring and tailored-feedback. SM-EMAdevelopment has begun during the preparation of this application, so our team is well-prepared to immediatelyimplement the study once funded.",2020,2023,Johns Hopkins University,370183,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2018 +C07095,3R01AA021771-08S1,The effect of the COVID-19 pandemic on alcohol use and psycho-somatic health in pregnant and postpartum women with intersecting vulnerabilities.,"SUMMARY/Abstract: The new clinical guidelines for diagnosing Fetal Alcohol Spectrum Disorders (FASD) list self-regulation as oneof the key behavioral deficits in children affected by prenatal alcohol exposure (PAE). There is a fundamentalgap in knowledge about the underlying mechanisms, spectrum, and severity of such deficits early in life and thebest analytical approaches to identify them. In addition, the effect of prenatal stress and postnatal environmenton PAE-induced alterations is poorly understood. The primary focus of the parent Ethanol, Neurodevelopment,Infant, and Child Health 2 (ENRICH-2) study is on identification of neurobehavioral deficits associated with PAEearly in life. This administrative supplement will allow us to examine the comorbid effect of COVID-19 pandemicand alcohol use on adverse maternal and infant outcomes in this cohort. The long-term goal of this supplementis to characterize the psycho-social effect of COVID-19 pandemic on adverse outcomes, including alcohol use,in a longitudinal birth cohort study, thus providing the foundation for future intervention studies. The objective ofthis supplement is to comprehensively evaluate the effect of COVID-19 related stress in pregnant andpostpartum women enrolled in the ENRICH-2 cohort. We will evaluate this by adding state-of-the-art self-reported measures integrated with real-time physiological data that are not currently part of the funded parentstudy. The rationale for this supplement is driven by the gap in knowledge about the effect of the COVID-19pandemic on psychosocial outcomes, alcohol use, and stress-related physical outcomes in pregnant andpostpartum women, a vulnerable population disproportionately affected. We will address this gap in knowledgeby pursuing two specific aims which evaluate the effect of COVID-19 on adverse maternal and infant outcomesin the ENRICH-2 cohort: 1) psychosocial outcomes and alcohol use, assessed as COVID-19 stress related toexposures and symptoms, COVID-19 pandemic adjustment, emotion regulation, mother-infant attachment, andalcohol consumption and 2) physiologic outcomes assessed as heart rate variability and sleep patterns,evaluated by wearable electronics - an approach particularly novel in the current social distancing environment.This approach is highly innovative, and will allow for the objective, real-time data collection in the climate ofprolonged social distancing and challenges associated with face-to-face research visits in vulnerablepopulations. A detailed characterization of COVID-19 related outcomes in pregnant and postpartum women,effect of COVID-related social isolation and other hardships on mental health and alcohol use, as well as thecumulative effect on pediatric neurodevelopmental outcomes are highly significant in order to lay out thefoundation for early effective interventions to mitigate the effects in these vulnerable populations.",2020,2023,University Of New Mexico Health Scis Ctr,134896,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts,2013 +C07096,3R01DA012237-20S1,Pittsburgh Girls Study: Substance Use and HIV Risk Behaviors/STI in Young Adulthood,"Abstract: This 1-year supplement to the Pittsburgh Girls Study (PGS), a large longitudinal community study of youngadult women, will capture urgently needed data on factors at individual (e.g., smoke or vape tobacco/nicotine,cannabis), social (family, peer), and neighborhood (e.g., perception of neighborhood disorganization) levelsassociated with increased risk for COVID-19 infection and illness progression, particularly among young adultwomen who smoke or vape tobacco or cannabis. Data to be collected with supplemental funds will add newCOVID-19 items to the PGS's 20th annual wave (web survey) in the two youngest cohorts (ages 24-25;N=1,048; 56% Black, 37% White), to be fielded in early June 2020, after the estimated peak in COVID-19-related mortality in Pennsylvania. New COVID-19 items will assess symptoms and related testing and healthcare (e.g., barriers to care, insurance), beliefs regarding transmission and personal infection risk, infectionprevention behaviors, and the broad impacts of COVID-19 on quality of life (e.g., job loss, food insecurity). NewCOVID-19 items to be included in wave 20 will add to 19 annual waves of PGS data collected since childhoodon substance use/disorder (SUD), physical health (e.g., diabetes, asthma, obesity, cardiovascular disease)and healthcare, mental health, personal (e.g., employment, resilience), and environmental (e.g., geocodeddata) risk and protective factors associated with risk for sexually transmitted infection/HIV (parent R01). Thissupplement aims to: (1) investigate differences by race among Black and White young women in pathways ofrisk and protection for COVID-19 infection and progression at individual (e.g., smoking and vaping behavior;perceived risk for and behaviors to prevent COVID-19 infection), social (e.g., extent and duration of socialdistancing), and neighborhood levels (e.g., perceived community cohesion, census tract population density);and (2) examine impacts of COVID-19 on women's substance use/SUD, access to and use of COVID-19-related health care, physical and mental health (e.g., response to stress/traumatic event), employment andfinancial status, and interpersonal relations (e.g., effects of social distancing). Results from this 1-yearsupplement have implications for addressing racial disparities in risk for COVID-19 infection and its broadimpacts, in the context of COVID-19's intersection with substance use/SUD (particularly smoking/ vapingtobacco, cannabis), among women, an understudied population, to guide effective and equitable public policy.",2020,2021,Rutgers The State University of New Jersey,132008,Human Populations,Black | White,Unspecified,Unspecified,Drug users | Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Economic impacts,2000 +C07097,3R01MH122213-01S1,Supplement: Long-term Effects of the Family Check-up on Depression and Suicide Across Trials and Development,"Project Summary This application, submitted as an Urgent Competitive Revision in response to NOT-MH-20-047, ""Notice ofSpecial Interest (NOSI) regarding the Availability of Administrative Supplements and Urgent CompetitiveRevisions for Mental Health Research on the 2019 Novel Coronavirus,"" represents a change in scope from ourcurrently-funded R01, which seeks to examine the long-term crossover effects of the FCU on depression andsuicide-risk using Integrative Data Analysis across three randomized trials. These randomized trials include alarge sample of children and families who received the FCU in early childhood and middle school. At that time,the FCU was delivered as an in-person model, and was adapted for both school and home delivery. Since thattime, the FCU has been adapted to an online version which has been effective with middle school youth atenhancing parenting self-efficacy and reducing child emotional problems (Stormshak et al., 2019). Given thewide-ranging negative effects of the COVID-19 pandemic on parent and child functioning, there is an urgentneed for effective family-focused prevention/intervention programming that can employ telehealth-deliveryformats to reach families in the midst of the current pandemic and future public health crises of similar scale.The proposed administrative supplement will adapt and test the efficacy of the Family Check-Up Online as atreatment to foster resilient family functioning in response to the COVID-19 pandemic. We will test the effectsof the adapted FCU Online program in a randomized clinical trial with 150 families with youth aged 10 - 14years, and assessed over 4 time-points across 6 months. We will examine the effects of the adapted FCUOnline on key mechanisms of change, including parenting skills, parental depression, and parent/child self-regulation, that we predict will directly impact child and family functioning. We predict that changes in these keytargets of the intervention will impact participant's response to the COVID-19 pandemic, including youthdepression and behavior problems, the ability to cope with pandemic-focused stressors (e.g. dealing withchanges in employment status or functioning; following mandated safety measures), and social/familialfunctioning (including relational support and risk for domestic violence).",2020,2022,Case Western Reserve University,481788,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C07098,3UM1AI068617-14S1,CoVPN 5002: SARS-CoV-2 Prevalence Study,"Abstract: The proposed research, CoVPN 5002, will directly contribute to preparedness for SARS-CoV-2vaccine and other COVID-19 prevention and treatment studies by determining the prevalence ofSARS-CoV-2 infection and seroprevalence among samples of individuals at elevated risk as well asthe general population. This research will determine the extent to which children and adults in thestudy communities have SARS-CoV-2 infection or evidence of prior SARS-CoV-2 infection (based onantibody tests, self-report, and medical records). Additionally, about participants' household memberswith COVID-like illness and deaths, combined with serologic data from participants, may also provideinformation about transmission dynamics within households. Questionnaire data will inform estimatesof the percent of individuals of different age groups, including children, who may have had anasymptomatic COVID-19 infection. The frequency of infection among children and whether childrenplay an important role in community transmission is poorly understood. The study will also estimatethe association of SARS-CoV-2 seroprevalence with medical co-morbidities associated with moresevere disease outcomes and identify demographic and social risk factors associated with infection.Finally, this research will provide important information about SARS-CoV-2 transmission, COVID-19disease, attitudes about and uptake of containment and mitigation measures, racial and ethnic healthdisparities, varied access to testing and public health resources by key demographicindicators, prospects for new prevention and treatment strategies, and inform mathematical models ofdisease progression and projection of future COVID-19 risk.The HPTN SDMC, housed at the Fred Hutchinson Cancer Research Center in Seattle, takesadvantage of the strengths of the institution, which also includes the HVTN SDMC. The HPTN SDMChas faculty biostatisticians experienced in the design, conduct and analysis of global clinical trials andsurveillance studies, who support research through leadership in statistical design, trial conduct andanalysis, and development and implementation of innovative statistical methods as needed andmotivated by the scientific goals. The SDMC provides regulatory compliant data managementfunctions for all trials it implements, including electronic data capture directly from research sites orthe field, integration of laboratory specimens and assay results, and electronic participant reportedoutcomes.",2020,2020,Fred Hutchinson Cancer Research Center,295993,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C07099,3R01AG054366-05S1,Predictors of Recovery and the App-Facilitated Tele-Rehabilitation (AFTER) Program for COVID Survivors,"PROJECT SUMMARY/ABSTRACTOlder adults and adults with comorbidities or disability are at highest risk for morbidity and mortality fromCOVID-19, although many healthy middle-aged adults without underlying risk factors also experience severedisease, likely driven by a profound and exaggerated inflammatory response. Those who develop severeCOVID-19 with acute respiratory distress syndrome often require prolonged mechanical ventilation and havelimited contact with hospital personnel, including rehabilitation providers, due to infectivity and shortages ofadequate personal protective equipment. Even patients with less severe COVID-19 who do not requireintensive care unit (ICU) care often experience prolonged fatigue, myalgias, and activity-limiting dyspnea.While the long-term consequences of COVID-19 are not yet known, the combination of immobility, limited in-hospital interventions, and heightened inflammation may have detrimental effects on physical function lastingwell beyond that seen with other critical illness. The overarching hypothesis is that both older adults withmultimorbidity and healthy middle-aged adults who experience the `accelerated aging' effects of profoundinflammation associated with COVID-19 will experience significant ongoing physical and neuropsychologicalimpairment. Novel, scalable interventions that can overcome many of the barriers imposed by COVID-19 areurgently needed to reverse physical and neuropsychological impairments and prevent the long-term functionalconsequences. Aim 1 will determine predictors of improved post-hospitalization recovery of adults recentlyhospitalized with COVID-19. Aim 2 will investigate the feasibility and initial efficacy of a multicomponent tele-rehabilitation program during COVID-19 recovery. This study will enroll 300 adults recently hospitalized due toCOVID-19 and follow these individuals for 16 weeks post-discharge using telehealth; Aim 2 will enroll a subsetof 40 individuals from Aim 1 who required ICU care for at least 24 hours, who will be compared to similarcontrols in Aim 1. Significance of the proposed work is based on the great need to identify predictors ofmultisystem recovery and long-term health in survivors of COVID-19, and to deliver safe and effectiverehabilitative care to medically complex patients even, and especially, when they face post-hospitalizationbarriers to in-person care. This work will directly translate to other medically complex populations who willbenefit from innovative tele-rehabilitation, which has not yet been applied to medically complex patients. Thisstudy will contribute immediately to our knowledge of the course of recovery for survivors of COVID-19 andpredictors for prolonged impairment during COVID-19 recovery. Furthermore, it will advance the feasibility oftele-rehabilitation as a more generally useful intervention in medically complex patients lacking access(distance, availability, mobility) to standard rehabilitative services. Developing safe and effective tele-rehabilitation programs as alternatives to in-person rehabilitation for medically complex populations couldtransform post-hospital care for medically complex patients including, but not limited to, those with COVID-19.",2020,2021,University Of Colorado Denver,523492,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2016 +C07100,1R21AI158568-01,Targeting SARS-Related Coronaviruses with a D-peptide Entry Inhibitor,"Project Summary The 21st century has seen the emergence of multiple lethal human coronaviruses (SARS-CoV, MERS-CoV,and now SARS-CoV-2). There is an urgent need for therapeutic options to combat the current and inevitable future SARS-like pandemics. Coronaviruses infect cells using a conserved entry mechanism shared by viruses across multiple families (including HIV, Ebola, and influenza) in which two regions of the trimeric viral spikeprotein (HR1 and HR2) collapse to form a highly stable six-helix bundle structure that forces the viral and cellular membranes together, inducing membrane fusion. Inhibitor binding to HR1 blocks six-helix bundle formation and stops viral entry, preventing infection. Our lab specializes in mirror-image phage display (MIPD),an innovative approach to identify novel synthetic protease-resistant D-peptide drug candidates, with a specialfocus on the inhibition of viral entry (with our HIV-1 drug, CPT31, set to begin clinical trials). D-peptides (peptides composed of mirror-image D-amino acids) cannot be digested by proteases in the body and,therefore, possess significant therapeutic advantages including extended half-life, lower dosing, reduced immunogenicity (not digested for MHC presentation), and durability in protease-rich environments such as therespiratory tract. To address the current health crisis, we are expediting our drug discovery process to identify D-peptide entry inhibitors that target the conserved HR1 of SARS-related coronaviruses. We have designed, synthesized, and characterized our HR1 mimic drug targets and are using them in MIPD to identify D-peptide inhibitors of 6-helix bundle formation and viral entry. In this proposal, we will chemically synthesize the D-peptides identified by MIPD and characterize their target affinity (using surface plasmon resonance) and antiviral activity against SARS-CoV and SARS-CoV-2 pseudoviruses. Promising D-peptides will be affinity-matured using a second round of MIPD to optimize potency. Using our custom-designed PEG scaffold (the backbone of CPT31), we will trimerize the highest affinity D-peptide candidates to improve avidity for the trimeric spike target and attach a membrane-localizing group, such as cholesterol, that will enrich the D-peptide at the cellular site of viral entry and improve in vivo half-life. These leading D-peptides will be tested against authentic virus (in collaboration with USU's Institutefor Antiviral Research). Our objective is to have one D-peptide candidate with ≤100 nM in vitro EC90 against SARS-CoV-2 and SARS and a good therapeutic index (EC50/CC50 >100) to advance to in vivo PK and efficacy studies, using USU's hamster model of SARS-CoV-2 infection. At the end of the grant period, we expect to have one D-peptide lead with demonstrated in vivo animal efficacy, poised for IND-enabling preclinical studiesand development as a SARS-related coronavirus treatment and/or preventative.",2020,2022,University Of Utah,429481,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07101,3U01DK124166-01S1,"Follow-up on Subjects, Integrative Data Analysis and Measurement of Viral Antibodies in The Environmental Determinants of Diabetes in The Young Study (TEDDY)","The University of South Florida is uniquely qualified to conduct the activities specified in this limited competition RFA. The purpose of the RFA is to fund the continuation of the Data Coordinating Center's (DCC's) functions in support of TEDDY subject follow-up and to add funds for studies of viral markers (antibodies), including COVID-19 and the integrative analysis of omics data. Competition will be sufficient to attract applications from collaborators with the capability to perform reliable measurements of viral markers, and to make the data available to TEDDY investigators for collaborative, integrative analyses. The proposed Data Coordinating Center activities include: 1) Executing the study protocol for follow-up of TEDDY study participants according to schedules and procedures contained in the study's Manual of Operations and incollaboration with the Clinical Centers at which participants are enrolled and with NIDDK staff. 2) Receiving,managing, and analyzing data obtained from the clinical centers 3). Monitoring of adherence to the research plan by conducting site visits to monitor the quality of record keeping, source documentation and the accuracyof data entry and also for overseeing data quality control. Steering Committee, subcommittee, and external evaluation committee meetings and workshops. 4). Providing statistical support, expertise and oversight throughout the study. 5) Providing study-wide communications, dissemination of study materials such asprotocols, Manual of Operations, forms or other study documents, and development and maintenance of the web site. 6) Playing a key role in the operational conduct of TEDDY, providing training and technical assistance to the Clinical Centers in performance of the follow-up assessments; assisting in protocol implementation; and working in conjunction with the Clinical Centers and NIDDK staff to oversee all aspects of Clinical Center performance, including timeliness and quality of data and biosample submission. 7) Procurement and administration of subcontracts for laboratory services, including: central human leukocyte antigen laboratory; the autoantibody laboratories, the mRNA laboratories, infectious disease laboratories, and other laboratories as needed. 8) Providing administrative and logistical support services for the TEDDY StudyGroup including preparation of publications, and organizing periodic meetings for the study group and subcommittees, workshops, and conference calls. 9) Transfer of all biosamples and data to the NIDDK central repositories according to a timeline developed with the NIDDK. and 10) Working closely with the ClinicalCenters in a collaborative and interactive manner and serving on the Steering Committee. The solicitation of external collaborators for studies of viral markers and integrative analyses will follow established mechanisms for soliciting and evaluating proposals. The DCC has successfully done this for several core TEDDY labs and this would be the third solicitation for integrative data analysis.",2020,2023,University Of South Florida,1124836,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2020 +C07102,3UG1CA239771-02S1,A Period Seroprevalence (SARS-CoV-2) Survey in MHCCN Cancer Healthcare Workers (HCWs) Providing Patient Care during the Height of the Outbreak: A Registry Study,"In December 2019, the emergence of an as yet uncharacterized pneumonia in Wuhan, China heralded the onset of the coronavirus pandemic caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). The etiology and disease profile, aka Coronavirus Disease-2019 (COVID-19), has been quickly elucidated; though there is considerable lack of understanding of viral transmission. Public health measures to mitigate and contain the outbreak are hampered by scarcity and scaling up testing. The virus is among the most contagious in our lifetimes and thought to be primarily transmitted by droplet infection. Viral transmission also occurs by airborne routes and during asymptomatic periods of infection, which complicates public health measures. This is further compounded by lack of Personal Protective Equipment (PPE) and different strategies for use. These realities place Healthcare Workers (HCWs) at risk providing care to known infected patients and Persons Under Investigation (PUIs) with high suspicion of COVID-19. We propose a hypothesis-driven period sero-prevalence study of SARS-CoV-2 in MaineHealth Cancer Care Network (MHCCN) cancer Healthcare Workers (HCWs) at a sizeable rural health system and academic medical center. Our study is predicated on the lack of sound sero-epidemiological data to define occupational exposure and risk of SARS-CoV-2 infection in our cancer providers. We anticipate brisk recruitment of our cancer HCWs (Aim 1) and roll-out of a sero-antibody (IgG/IgM) test (Aim 2) to determine exposure. Brief clinical and occupational surveys will be completed. This cohort is invaluable to sustain and provide information on the SARS-CoV-2-transmission dynamics that will guide continued response to this pandemic, especially with an anticipated second wave that will inform cancer care in the rural community setting. This project is submitted in response to NOT-CA-20-0421 and is closely integrated and tethered to MaineHealth Lifespan NCORP (1UG1 CA239771-01) the parent grant that was submitted and subsequently awarded under PA-18-591.",2020,2025,Mainehealth,128919,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease surveillance & mapping,2019 +C07103,3R01LM013309-02S2,Collaborative Research: Statistical Algorithms for Anomaly Detection and Patterns Recognition in Patient Care and Safety Event Reports,"Project Summary: Medical errors have been shown to be the third leading cause of death in the United States. The Institute of Medicine and several state legislatures have recommended the use of patient safety event reporting systems (PSRS) to better understand and improve safety hazards. A patient safety event (PSE) report generally consistsof both structured and unstructured data elements. Structured data are pre-defined, fixed fields that solicitspecific information about the event. The unstructured data fields generally include a free text field where the reporter can enter a text description of the event. The text descriptions are often a rich data source in that the reporter is not constrained to limited categories or selection options and is able to freely describe the details ofthe event. The goal of this project is to develop novel statistical methods to analyze unstructured text like patient safety event reports arising in healthcare, which can lead to significant improvements to patient safety and enabletimely intervention strategies. We address three problems: (a) Building realistic and meaningful baseline modelsfor near misses, and detecting systematic deterioration of adverse outcomes relative to such baselines; (b) Understanding critical factors that lead to near misses & quantifying severity of outcomes; and (c) Identifying document groups of interest. We will use novel statistical approaches that combine Natural Language Processing with Statistical Process Monitoring, Statistical Networks Analysis, and Spatio-temporal Modeling tobuild a generalizable toolbox that can address these issues in healthcare. We will also release open sourcesoftware via R packages & GitHub, which will enable healthcare staff and researchers to execute our methods on their datasets. The COVID-19 pandemic has resulted in increased patient volumes and increased patient acuity, leading to an excessive burden on many healthcare facilities across the United States. This greatly increases the risk of patient safety consequences arising from malfunctioning medical equipment or adverse reaction to medication. To ensure patient safety and the highest quality of healthcare during this crisis, we need a rapid response system to model and analyze COVID-specific safety issues at scale, and quickly disseminate the results to healthcare facilities, so that these risks can be mitigated at the point of care. In this supplement, we propose to do this by (a) mining public databases and EHRs to identify devices/medication being used for treating COVID and (b) applying our methods (based on NLP, SPC, and SPM) to understand risks associated with these items. This information will be disseminated nationally to all healthcare facilities so that it can be integrated into the EHR at the point of care to alert clinicians.",2020,2021,North Carolina State University Raleigh,74963,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2020 +C07104,3P42ES010337-19S1,DETECTION AND MODELS OF TOXICANT EXPOSURE,"Abstract: The novel SARS-CoV-2 coronavirus, the causative agent of COVID-19, can establish fatal lower airway infections. Such infections can in some cases, strongly affected by a variety of risk factors and co-morbidities,can progress to acute respiratory distress syndrome (ARDS), the major cause of death medical condition the entails uncontrolled lung inflammation and injury and can lead to metabolic collapse and multiorgan failure. Anti-inflammatory treatment that effectively prevent ARDS initiation and propagation should reduce the high levels of morbidity and mortality associated with COVID-19 and thereby save many lives and billions of healthcare dollars. Other than glucocorticoids, no such treatments have been developed. Moreover, while glucocorticoids inhibit inflammation they have strong immunosuppressive activity and can therefore prevent the acquisition of longlasting anti-viral immunity. COVID-19 ARDS is initiated by viral-induced killing of lung epithelial cells and the release of damage associated molecular patterns (DAMP) of which IL-1α primes macrophages, ATP triggers NLRP3 inflammasome assembly and activation, a key event in the initiation of ARDS. NLRP3 inflammasomeactivation mediates the processing and secretion of IL-1β and IL-18, two potent inflammatory cytokines, whose circulating levels are elevated in ICU-admitted COVID-19 patients. COVID-19 associated ARDS and ARDS of all causes are age dependent and their risk can increase by up to 20-fold in older adults (65 years and above) who account for 80% of COVID-19 deaths. ARDS and COVID-19 risk are further increased by co-morbidities,such as obesity, type II diabetes (T2D) and fatty liver diseases as NAFLD, including both non-alcoholic andtoxicant induced steatohepatitis (NASH and TASH, respectively). The marked increase in ARDS risk posed by obesity, T2D and NAFLD may account for most of the socio-economic disparity in COVID-29 morbidity and mortality. We recently found that the commonly prescribed, safe and cheap anti-diabetic drug metformin caninhibit NLRP3 inflammasome activation in vitro and in vivo. Metformin, however, has a short half-life and macrophages do not express the metformin transporter present on hepatocytes. To increase metformin delivery to alveolar macrophages, we will generate metformin-loaded nanoparticles and will first test them for inhibitionor amelioration of LPS-induced ARDS. When the efficacy of inhalation metformin will be confirmed in that simple and rapid model, we will examine its efficacy in SARS-CoV-2 infected hACE2 transgenic mice, which provide a suitable model for studying COVID-19 related ARDS. We will also examine whether obesity, excessive fructose consumption and exposure to the environmental toxicant triclosan, a potent induce of TASH, increase ARDS severity in both models and whether inhalation metformin mitigates these effects.",2020,2022,University Of California-San Diego,408869,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Prophylactic use of treatments,2000 +C07105,3U19MH113203-04S3,StepWell: Stepped Care Mental Health and Substance Use Telehealth Services for COVID-19 Affected Patients,"Social isolation, economic insecurity, and rapid increases in numbers of COVID-19 cases and deaths are resulting in alarming rates of mental health and substance use disorders. Furthermore, existing social, health,and mental health (MH) disparities among racial/ethnic minorities have exacerbated. MH care systems and collaborative care systems, which integrate MH into primary care settings, have been hard pressed to provide psychiatric care to new patients with MH and substance use (SU) disorders (MHSUDs) arising from the pandemic- including patients recovered/ recovering from COVID-19 (""COVID survivors"") and their families. The necessity of using telehealth strategies to protect patients and providers has posed additional challenges for MH/SU caresystems. Although telehealth may increase patient engagement, no research has identified optimal, resource-efficient strategies for its use in MHSUD screening and care delivery. Thus, a novel approach that meets both the demand and the safety challenges of the COVID-19 era is required to address the burgeoning COVID-related MHSUD care needs. Coupling a stepped-care strategy with automated triage, psycho education, and shared decision-making can not only address capacity and system-level barriers, but also potentiate treatment effects and address patient/provider-level barriers to engagement. To meet the critical MH challenges presented by the COVID-19 pandemic, the proposed supplement research will adapt and apply a technology developed in the parent grant, the Electronic Mental Wellness Tool (EmwT), that guides providers in screening patients for any MHSUDs using 3 validated items with high sensitivity and then, using another 9 validated items, triages patients to specific evidence-based treatments according to diagnostic categories with good specificity. The initial 3 items also can detect, by proxy and with high sensitivity, any MHSUDs among relatives. We will extend this work to develop and implement StepWell, a telehealth stepped-care approach to MHSUD treatment that integrates the EmwT with an electronic patient-facing depression and anxiety care shared decision-making tool in use at New York Presbyterian Hospital (NYPH). In a new cohort of 1,000 recently discharged COVID patients being followed by NYPH for one year, we will test the feasibility of using StepWell to identify MHSUD problems among COVID survivors and their families and address their MHSUD treatment needs while monitoring MH outcomes for 1 year. We will use human-centered design principles to integrate the eSDM (patient preference) and EmwT(assessment and treatment) technologies to develop StepWell. In a mixed-methods pilot test, we will examine feasibility, acceptability, and factors influencing StepWell implementation in preparation for a larger implementation science R01 proposal. This project addresses calls to monitor and address the MH impact of COVID-19 infected and affected patients, while expanding the ability of the health systems to address the existing treatment gap to provide a sustainable, generalizable MH services solution beyond the COVID-19 crisis.",2020,2022,Columbia University,411638,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2017 +C07106,3U54CA190155-05S2,Seroprevalence of COVID-19 of cancer patients in Tanzania,"The SARS-coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide causing the global pandemic. There are a number of comorbidities and risk factors associated with COVID-19 and cancer patients could be at particular higher risk since they tend to be older, likely to have multiple comorbidities, and are often immunosuppressed due to the disease and cancer treatment. Our team has been collaborating with the Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania through an NCI U54 CA190155 Cancer Research International Training and Intervention Consortium project to study HIV/AIDS associated cancers in Tanzania. As part of that collaboration, we investigated the prevalence of a number of other common infectious agents in the population, such as the Kaposi's sarcoma herpesvirus, hepatitis and HIV, by testing plasma collected from cancer patients and blood bank donors. Because this collection was prior to the COVID-19 pandemic, we have retested some of them recently and have detected antibody responses that appear to target the SARS-CoV-2 proteins. This suggests that cross-reactive antibodies were present in a portion of the Tanzanian population prior to the outbreak, which could confer some protection against SARS-CoV-2. Thus, our overall objective is to develop a better understanding of potential immunological factors that may contribute to partial protection against SARS-CoV-2 infection and COVID-19 disease pathogenesis in cancer patients in Tanzania. We hypothesize that cross- reactive antibodies against different strains of coronaviruses in Africa are present prior to the pandemic, which will provide cross protection to prevent an increase of SARS-CoV-2 infection and COVID-19, in both cancer patients and the general population in Tanzania during the pandemic. Our specific aim is to determine and compare the prevalence of anti-SARS-CoV-2 antibodies among cancer patients and the general population, prior to and during the current COVID-19 pandemic. This will be carried out by: a) analyzing the cancer patients plasma collected by our ongoing U54 current prior to the pandemic and those collected from a prospective cohort of cancer patients recruited during the pandemic by this proposed study, for the presence of anti-SARS-CoV-2 antibodies; b) analyzing a large panel of normal blood donors collected prior to the pandemic and a second panel collected prospectively by this study during the current pandemic; c) compare the prevalence of anti-SARS-CoV-2 antibodies between cancer patients and the general population before and during the current pandemic. The proposed study is significant and timely because it will synergize with our ongoing U54 project and utilize its collected patients' specimen, to determine the protective effect of cross-reactive antibodies to SARS-CoV-2 in both HIV-1 infected and uninfected cancer patients in comparison to the general population, both prior to and during the current pandemic.",2020,2021,University Of Nebraska Lincoln,147415,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Africa | Americas,,,,United States of America,Tanzania | United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +C07107,3UH3CA246594-02S1,"Multiplexed imaging of Renin-Angiotensin System (RAS) pathways, endothelial and immune dysfunction in COVID-19 Lung","PROJECT Summary: SARS-CoV2 pandemic has already taken a high toll with ~700,000 (~155,00 US) deaths and 18 million (~5 million US) infections globally with unabated spread in many countries and new hotspots reemerging on a regular basis. While frantic efforts are underway to develop vaccines and therapies and there is high hope that these will be available over the next 6-12 months, there are no answers to how much and how long these will be effective. A continued effort on understanding the disease etiology, particularly in the organ first infected, and identifying new avenues of intervention therefore is important. The major route of virus infection is via the respiratory tract and virus is reported tospread via lung to other organs by vascular leakage by directly (through infection) or indirectly (byimpairing ACE2 activity) affecting the endothelial and immune cells. Cells expressing ACE2 enzyme and other viral coreceptors (TMPRSS2 or Cathepsin L) are the major targets of viral infection. ACE2 is a key player in regulation of the Renin-Angiotensin system (RAS) pathway. By converting theproduct of ACE activity, angiotensin II (ang II), to angiotensin 1-7 (ang 1-7), ACE2 diminishes Ang II mediated deleterious effects that can include promoting vascular wall inflammation, endothelial dysfunction, endothelial cell and vascular smooth muscle cell migration, growth, proliferation, and thrombosis. Disruption of ACE2 by viral binding may reduce this protective effect. The inhibition of nitric oxide production, activation of megakaryocytes, complement and platelets can also cause thrombosis and thrombolytic dysfunction leading to clot formation in lung arteries and other organs.Since the early unprecedented global effort to identify the cellular targets of SARS-CoV2 using single cell RNA sequencing (scRNAseq) data from multiple human and non-human single cell datasets,several in depth reports on individual organs infected and cells and cellular pathways affected by this virus have appeared. Most of these reports are based on transcriptomic analysis of homogenized or disaggregated samples although some singleplex immunofluorescence analysis have been reported. COVID-19 tissue histology shows a very heterogenous disease which may be a function of multiple factors including cellular composition, spatial organization and neighboring cell activation. To understand these factors, here we propose an in situ multiplex immunofluorescence study of SARS-CoV2 positive and negative patient samples to spatially profile the cell types affected in the upper and lower respiratory tract and the role of RAS pathway activation in endothelial and immune cell dysfunction related to COVID-19 morbidity and mortality.",2020,2022,General Electric Global Research Ctr,99973,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2019 +C07108,3P42ES027723-01A1S1,Impact of Airborne Heavy Metals on Lung Disease and the Environment,"Our current P42 project (Project 5) deals with natural and recycled fiber materials for filtration targeted toward soil remediation. This supplemental funding request (for Project 5) directly addresses the needs of the growing COVID-19 pandemic, with the base theme of natural fibers as filtration media for personal protection.The rapid spread of the COVID-19 pandemic exponentially increases the risk to the P42 community not only from the soil/air contamination with particulate matter and heavy metals, but now the added risk of the virus. Providing low cost reusable and biodegradable personal protection equipment (PPE) solutions to the community will be of immense value. One of the most needed items are PPE masks not only for the health care provider but the public at large. There is growing use of masks of all make ups and configurations, and their use is goingto multiply exponentially. The various federal briefings have emphasized the need for a mask for every person, and over 500 million masks could be worn on daily basis world-wide. Hundreds of millions of N95 masks are inproduction and use worldwide. For the most part, these are disposed after single use (2-3 times at the most) which will result in gigantic quantities in landfill. This will result in massive detrimental environmental implications for years to come. In this project we propose innovative yet practical science to develop natural fiber (biobased) biodegradable filter materials that will meet the NIOSH standards for N95 filter efficiency (FE). The biobased solution is based on sub-micron regenerative cellulose natural fibers (RNCF) and small amounts of textile gradecarbon fiber (TCF) that will be designed for turboelectric charging that impart the interaction to capture and kill the virus(es). The RNCF based filter material will be equally effective in lieu (or complement) of the synthetic polypropylene (PP) based 2 µm diameter, 50 grams per square meter (gsm) filter materials (not biodegradable)currently used in the N95 masks. The work will deliver a tangible full concept to product solution for implementing the RNCF material in reusable masks that the team is already developing. The entire solution will beenvironmentally friendly, safe and will meet NIOSH standards. The materials developed in this project will be tested against the NIOSH 42 CFR 84 for a minimum 95% filtration efficiency against solid and liquid aerosols that do not contain oil. The product will be disseminated to the P42 ecosystem including the health care providers and the community. The feedback from these groups will be sought in the form of surveys, questionnaires, training and the data will be statistically analyzed and become a part of the main P42 grant. The project is collaborative between The University of Tennessee (UT), Oak Ridge National Laboratory (ORNL), University of Alabama at Birmingham and the P42 community.",2020,2025,University Of Alabama At Birmingham,112393,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07109,3R01ES028250-03S1,Reduction of Hazardous Exposures in Small Businesses through a Community Health Worker Intervention,"PROJECT Summary: This administrative supplement application is in response to NOT-ES-20-020, which calls for proposals assessing the impact of Coronavirus 2019 (COVID-19) on environmental exposures. Our parent project aimsto reduce negative health outcomes in small businesses that primarily employ high-risk Latinx workers by characterizing their exposures to hazardous chemicals and assessing if a community health worker (CHW)intervention can decrease these exposures. Workers in small businesses may have increased risk of COVID-19 exposure and severe economic impacts due to social distancing and shelter-in-place guidelines. In addition,small businesses may be unable to obtain needed personal protective equipment and may significantly increase their cleaning practices, and thus their chemical exposures. Small businesses are more likely to employ low-wage Latinx workers, and use hazardous solvents, including volatile organic chemicals (VOCs),that can cause asthma and cardiovascular disease which are risk factors for COVID-19 complications. Yet their workers lack access to culturally and linguistically appropriate occupational health information, including for COVID-19. Due to social distancing and shelter-in-place guidelines, we currently cannot measure chemical exposures or conduct face-to-face CHW interventions. The primary goal of our supplement application is to enhance our relationships with our small business partners by responding to their immediate needs during theCOVID-19 pandemic and helping them through the crisis, while promoting worker safety through a novel tele-promotora program. CHWs are an innovative method to bridge the gap between small businesses and other stakeholders. The proposed project will capitalize on the strong, established partnership between the University of Arizona, the Sonora Environmental Research Institute, Inc., and the El Rio Community HealthCenter. A community-engaged research framework will be used to complete the following specific aims: 1) develop a novel ""tele-promotora"" program to deliver occupational health information to these vulnerable small business owners while face-to-face interactions are not possible; 2) determine how the COVID-19 pandemic has changed VOC exposures in two high-risk industries: auto repair shops and beauty salons; and 3) assess competing risk perceptions regarding COVID-19, economic impacts, and hazards of VOC exposures. These proposed aims directly relate to our previous aims, regarding: 1) assessing workplace exposures and risk perceptions in these two industries and 2) developing a CHW-intervention. It is essential that we gather information on COVID-19 impacts and update our CHW intervention in order to be sensitive to these concernsduring the cluster-based trial (Aim 3, parent). Completing this supplement will preserve and/or increase the intervention's impact by helping marginalized, Latinx workers and small business owners who may have limited education, literacy, and computer skills to understand the risks of COVID-19 and chemical hazards associated with their work, while empowering them to have greater control over their occupational exposures.",2020,2022,University Of Arizona,376908,Human Populations,Other | Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Communication | Indirect health impacts",2017 +C07110,3R01AT009562-04S1,Discovery of GPCR-active natural products and their biosynthetic genes from the human associated bacteria,"Project Summary: The development of therapies inspired by the human microbiome is at least in part limited by our lack of understanding of how human associated (HA-) bacteria communicate with their human host and affect pathogens. Human microbiome sequencing studies show strong correlations between changes in bacterial populations and human health. Despite these correlations and the evidence linking HA-bacteria to disease in mice, the mechanistic details of how HA-bacteria specifically affect mammalian physiology remain largely unknown. In other environments, bacteria are known to rely heavily on low molecular weight compounds (small molecules or natural products) to interact with other organisms. Similarly, we expect that HA-bacteria are likely to use small molecules to interact with their human hosts and pathogens. Mounting evidence suggests that, although each human microbiome is composed of a complex collection of bacteria, a much smaller number of species is highly prevalent across the majority of individuals. While we don't know exactly which HA-bacteria are responsible for maintaining human health or causing disease, we hypothesize that small molecules produced by these commonly encountered HA-bacteria are likely to play an important rolein these processes. The central aim of this proposal is to screen metabolites produced by the most commonly observed HA-bacteria in high-throughput bioactivity screening to identify GPCR and SARS-CoV-2-active small molecules and their producing biosynthetic gene clusters (BGCs). GPCRs constitute the largest family of eukaryotic trans-membrane receptors. They are known to play diverse and profound roles in human biology and are prone to regulation by small molecules. Based on the fact that GPCRs play such an extensive role intransforming chemical information from the environment into biological signals in eukaryotic cells, I believe that HA-bacteria likely affect host physiology through the production of small molecules that interact with GPCRs.The emergence of the SARS-CoV-2 virus represents a worldwide pandemic with no therapeutic drug treatments. The two Aims of this proposal will result in (1) the identification, isolation, and structure elucidation of HA-bacteria-encoded metabolites that either interact with diverse GPCRs or inhibit SARS-CoV-2, (2) the characterization of the gene clusters for these metabolites, and (3) the validation of their production by colonizing bacteria. These studies will help to illuminate the mechanistic details of how HA-bacteria shape human health. The human microbiome is reported to influence complex pathophysiological processes ranging from the regulation of the immune system to the development of the brain and the central nervous system. Changes in HA-bacterial populations are associated with diseases that affect over 200 million Americans including obesity, diabetes, inflammatory bowel disease, autism, irritable bowel syndrome, and cirrhosis among many others. Therapies derived from HA-bacteria have potential utility in controlling diverse basic biological processes and human diseases.",2020,2022,Rockefeller University,254250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis,2017 +C07111,3R01AT005378-10S1,Vitamin D fluctuations and the mucosal immune response,"Summary: Vitamin D supplements have been suggested as being useful in high doses for preventing and treating severe disease associated with SARS-CoV-2 infection (i.e. COVID-19). Vitamin D status has been shown to be low in patients with acute respiratory infections. Unfortunately, it is yet unclear whether those associations are causal. Currently, the mechanisms underlying the effects of vitamin D in the lung are not completely understood. In addition, there is not data that demonstrates that vitamin D or the active form of vitamin D (1,25(OH)2D, 1,25D) is effective for improving outcomes following a viral infection. The effects and timing of supplemental vitamin D will be tested on host resistance to SARS-CoV-2 infection in mice and hamsters. The basic mechanisms by which vitamin D regulates the immune response following a respiratory virus infection are critical for the safe and effective messaging for vitamin D supplementation. Understanding the mechanisms underlying the effects of vitamin D in the lung is needed to provide responsible guidance on whether it is safe and effective to supplement individuals with high amounts of vitamin D to protect from COVID-19 disease.",2020,2021,Pennsylvania State University-Univ Park,240750,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2009 +C07112,3RF1AG053303-01S2,A Multipronged Interrogation of Large-Scale Omics Data to Reveal COVID-19 Pathways,"The COVID-19 global pandemic has led to more than 470,000 deaths. This disease is especially perilousfor the elderly - 80% of deaths in the US have been individuals over the age of 65, and the social isolation created by lockdowns have increased risks of serious physical and mental health issues. COVID-19 is a heterogeneous disease exhibiting a broad spectrum of symptoms, ranging from mild (e.g.loss of smell, dry cough) to critical (e.g. cytokine storm, renal failure, cardiovascular damage, respiratory failure, lethal blood clotting, neurological disorders). This clinical heterogeneity demands a precision medicine approach that elucidates distinct pathways underlying the disease, develops treatments for each pathway, and defines biomarker patterns to diagnose patients for classification within the subsets. A key benefit of precision medicine is that drugs may be repurposed or may already exist to treat specific subsets of infected individuals. For example, one critical outcome for COVID-19 infection is the onset of a cytokine storm, in which the body's immune system gets caught in a positive feedback loop, leading to shock and rapid failure of multiple organs.There are existing drugs for treating cytokine storm syndrome, but practitioners have no clear guidelines if such treatments are beneficial or destructive. If the individual is not in a hyperinflammatory state, the administration of these drugs could cripple their immune response, leading to increased viral load. Plasma biomarker patterns of proteins and metabolites hold potential to identify impending cytokine storms and other lethal outcomes. To advance precision medicine for COVID-19 treatment, this work will generate large-scale omics data and evaluate levels of proteins and metabolites for plasma drawn from 350 COVID-19 positive cases and 750 normal controls. These data will be immediately released to the research community. Our research team will take a concerted multipronged approach for analyzing these data using diverse complementary techniques. Our labs' research focuses on the discovery of combinations of genes and proteins expressing synchronously and the associations of these combinations with traits of interest, as well as endophenotype discovery. In addition to thorough single analyte analyses, this research will employ three computational strategies to reveal combinations of factors defining patterns: 1) network modeling, 2) explainable-AI systems biology, and 3) linear programming. These intensive analyses will require significant computational resources and we will utilize Summit at Oak RidgeNational Laboratory, one of the most powerful supercomputers in the world, for these tasks. The comprehensive protein and metabolite profiles, based on a large cohort of COVID-19 cases and normal controls, along with our rigorous interrogation of these data for complex biomarker patterns indicative of patient outcomes, hold unprecedented potential to drive solid advances in precision medicine and to reduce mortality rates due to COVID-19. In addition, this research will provide an agile model for use when tackling other heterogeneous diseases plaguing humankind, as well as novel viruses that may arise in the future.",2020,2021,Washington University,650002,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2016 +C07113,3R24AG064191-02S2,Rapidly Disseminating Scientific Advances about Northwell Health COVID-19+ Clinical Care to Impact Health and Welfare of Persons across the Life Course in the United States,"This is an application under PA-18-935: Urgent Competitive Revision to Existing NIH Grants activatedunder Notice of Special Interest (NOSI): NIA Availability of Administrative Supplements and Revision Supplements on Coronavirus Disease 2019 (COVID-19) to revise our currently active R24: R24AG064191.The original purpose of the R24 Roybal Coordinating Center is to provide strategic leadership, efficient coordination, inspired support, and creative dissemination for the Edward R. Roybal Centers. We propose a competitive revision to this existing grant to meet immediate dissemination needs to help address the specific public health crisis by the Northwell Health COVID-19 Research Consortium. It is entitled ""Rapidly Disseminating Scientific Advances about Northwell Health COVID-19+ Clinical Care to Impact Health andWelfare of Persons across the Life Course in the United States."" We propose to do so under NOT-AG-20-022. We have created an IRB-approved registry data (""data mart"") on all COVID-19 suspected patients. The data mart includes all clinical, outcome, laboratory, socio-demographic, and geographic characteristics of persons presenting under suspicion for, being tested for, or diagnosed with COVID19. Specifically, it includes information needed to answer vital and urgent public health questions about how to detect, test, and manage patients with this disease. For example, it includes data from thousands of patients on mechanical ventilation status, use of hydroxychloroquine, chronic use of angiotensin-converting enzyme (ACE) inhibitors orangiotensin II receptor blockers, compassionate injection of serum donated from recovered COVID-19+ patients, as well as many other variables. Northwell is the healthcare system with the largest volume ofCOVID-19 patients in the country. As of April 3, 2020, we had a total of 5700 COVID-19+ confirmed patients (mean age, 62.4 years; 39.7% female; 20.1% Hispanic; 23.7% African American). Northwell Health is the largest academic health system in New York, with approximately 4,844 hospital beds and 672 ICU beds,serving approximately 11 million persons in Long Island, Westchester, and New York City. Because the pandemic is predicted to extend several seasons, we are requesting 2 years of support, to ensure that the long-term, as well as short-term, consequences of this pandemic can be fully and transparently reported. This is critical, because the social, economic, institutional, and policy environments addressing the COVID-19 pandemic may differentially impact the health and welfare of people across the life course and in vulnerable social and medical groups, such as those with Alzheimers or other related dementias. We have the data, resources, leadership will, and commitment to accomplish this mission. It would be highly impactful to rapidly address the research dissemination and productivity of the Northwell healthcare system to ensure that other healthcare systems can benefit from what we have learned and continue to learn in addressing this pandemic and addressing disparities in care.",2020,2024,Feinstein Institute For Medical Research,830694,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Post acute and long term health consequences,2019 +C07114,3K76AG059983-02S1,GAPcare II: The Geriatric Acute & Post-acute Care Coordination Program for Fall Prevention in the Emergency Department,"PROJECT SUMMARY Before the COVID-19 pandemic, only 4% of older adults used telehealth, but uptake has been rapid since the start of social distancing. However, little is known about physicians' experiences implementing telehealth or the extent of uptake among US physicians. There is a critical need to disseminate useful telehealth strategies that physicians have employed to treat older adults, especially those with disabilities (e.g. visual, hearing,mobility, cognitive), living in facilities, with limited digital know-how or access to technology. Through in-depth interviews with geriatricians, primary care, and emergency physicians, who are the first point of contact during COVID-19, and a subsequent national survey, we propose revealing these strategies, understanding the scope of telehealth uptake nationally, and disseminating our insights which could inform healthcare delivery transformation for older adults. The rationale that underlies the proposed research is that physicians have made important discoveries about telehealth since the start of COVID-19 and disseminating lessons learned will ensure that older adult needs are considered as care is rapidly shifted to the virtual environment. Without attention to equity and leveraging insights of physicians that care for older adults, the ""digital divide"" will cause already existing inequities in medical care to further increase at the expense of older adults. Identifying where telehealth has not yet been implemented can be helpful to focus awareness efforts. Dr. Goldberg will pursue thefollowing two specific aims: (1) conduct semi-structured telephone interviews (n=36-54) with geriatricians, primary care and emergency physicians (n=12-18 each), stratified by practice setting (metro/suburban/rural(n=12-18 each)) and type (academic/community (n=18-27 each)) to explore telehealth service sprovided/abandoned, modes of use, facilitators/barriers, practical considerations, and experiences with providing care remotely to older adults. We will solicit physicians on social media platforms (Twitter,Facebook), and via specialty society list serves. Findings will inform item generation, reduction, and question content for the survey; (2) conduct a web-based national survey of geriatricians, primary care and emergency physicians (n=1,600, 1% of each specialty) using the American Medical Association's Physician Masterfile to estimate the scope of telehealth use, methods of delivery, barriers/challenges to adoption, and lessons learned delivering care to older adults. This contribution is expected to be significant because the choices physicians make in adapting their clinical practice to the remote environment - what modes to use, how to train and assess patients - are likely to dictate if older adults' needs and challenges are considered as the future of healthcare delivery takes shape. Dr. Goldberg's overarching aims are to ensure older adults receive medical care in the most suitable setting by enhancing the knowledge and training physicians receive in telehealth to meet the unique needs of their patients during and after the pandemic. The completion of these aims will provide Dr.Goldberg with critical pilot data for a telehealth training RCT which will be submitted as a R01 to the NIA.",2020,2024,Rhode Island Hospital,66285,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health service delivery,2019 +C07115,3R01ES025166-05S1,Mechanisms of reversible DUB oxidation in genome stability pathways - Revision,"PROJECT SUMMARY/Abstract: The current pandemic of COVID-19 (Coronavirus Disease-2019), a respiratory disease that hasled to over 5 million confirmed cases and over 350,000 fatalities in over 100 countries since its emergence in late 2019, is caused by a novel virus strain, SARS-CoV-2, an enveloped, positive-sense, single-stranded RNA beta-coronavirus of the family Coronaviridae. My lab has a long-standing interest in understanding how cellular DUBs are regulated by environmentally-produced small molecules, including ROS, toxic heavy metals, chemical pollutants and carcinogens. Similar to human DUBs, viral DUBs, such as the coronavirus Plpro, are proteases that cleave ubiquitinor ubiquitin-like proteins from pro-proteins or from conjugates on target proteins. In doing so, viral DUBs hijack the balance of ubiquitination dynamics in infected cells, potentially disrupting numerous cellular functions, including cell cycle regulation, proteasomal and lysosomal protein degradation, gene expression, kinase activation, DNA repair and ultimately favoring microbial pathogenesis. How viral DUBs are particularly susceptible to environmental exposures, such as ROS and chemical pollutants, have not been adequately explored, especially as novel modulators of human pathogenesis. As it pertains to the rapid global spread of SARS-CoV-2 and the prevalence of COVID-19 disease in the U.S. population and worldwide, we will be focusing our research goals on understanding 1) how the SARS-CoV-2 Plpro protease activity (cleavage of pro-proteins, ubiquitin-, and ISG15-conjugated proteins) can be regulated by environmentally-generated small molecules, and 2) identifying COVID-19 disease-relevant cellular targets of thePlpro upon viral infection in human lung epithelial cells.",2020,2021,New York University School Of Medicine,354319,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C07116,3RF1AG061001-01S2,COVID 19 Respiratory and CNS Pathogenesis in Geriatric Rhesus Monkeys,"Project Summary: Although coronaviruses primarily cause respiratory and intestinal infections, they also have the potential to cause central nervous system (CNS) complications. There is accumulating evidence of neurological damage in COVID-19 patients, with neurological symptoms correlating with disease severity. The primary receptor for SARS-CoV-2, the angiotensin converting enzyme- 2 (ACE-2), is expressed by neurons and other cells in the brain providing a strong rationale to investigate the impact of SARS-CoV-2 infection on the CNS. The goals of this proposal are to understand CNS viral dissemination and neuroinflammation following SARS-CoV-2 infection in geriatric rhesus macaques. Because preventing viral entry into the CNS maybe a lifesaving measure in COVID-19 patients, this work is highly urgent. Additionally, susceptibility of geriatric patients to COVID-19 associated respiratory and CNS complications suggests a role for age-associated immunosenescence and neurodegeneration in COVID-19 morbidity. Addressing these questions in the framework of human studies is challenging; therefore, studies in the COVID-19 rhesus model are critically needed. The goal of this work is to urgently address CNS complications as it relates to age using a COVID-19 rhesus model. Our Aims are: Aim 1: Characterize SARS-CoV-2 dissemination to CNS and neuroinflammation in young and geriatric rhesus monkeys. Aim 2: Determine Efficacy of Convalescent Plasma Therapy in preventing COVID-19 respiratory and CNS complications in geriatric monkeys. Urgency and relevance to NOT-AG-20-022: This proposal aligns with the research interests of Division of Aging Biology and Division of Neuroscience. Our rhesus studies are focused on understanding disease pathogenesis in older animals and are highly relevant to scope and purpose of this NOSI. Work in animal models is vital to fully comprehend how SARS-CoV-2 gains access to the CNS and define crucial interventions to resolve infection without long-term neurocognitive damage. Feasibility: This urgent competitive revision is within the expertise of the PIs of the original grant and we have the resources, reagents, and collaborators at the CNPRC to achieve the proposed goals. We have included as Key Personnel, Dr. Chris Miller and Dr. Koen Von Rompay who are part of the CNPRC team developing COVID-19 rhesus model. Our strong collaborations with the UC Medical Center clinicians treating COVID-19 patientsgives us a significant advantage in understanding the disease process and identifying and testing interventions with direct translational relevance. Work in animal models is vital to fully understand how/why SARS-CoV-2 in more pathogenic in older adults, gains access to the CNS and to define crucial interventions to resolve infection without long-term pathology. All the lab work will be done in certified (by State, County, and UC systemregulators) BSL3 laboratories at the CIID and the AG BSL3 animal facilities at the CNPRC. The work has been approved by the UC Davis IBC and will be monitored by biosafety officers at UCD main campus,CIID, and CNPRC.",2020,2023,University Of California-Davis,780502,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2018 +C07117,3U01HG008657-06S1,"eMERGE SARS-CoV-2 Supplement: Pulmonary, renal, and inflammatory components","Abstract: As of May 4, 2020, more than 3.5M cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and 250,000 deaths have been reported worldwide, with more than 1.2M cases and over 70,000 deaths in the United States. The severity of infection varies from no symptoms to respiratory failure and death. Genetic factors appear to underlie some interindividual variability in SARS-CoV-2 infection outcomes. Part of this heritability may be associated with host immune response, as lymphocyte measures at hospital admission predict disease severity. It may be may also be important to understand whether an individual's underlying or ""baseline"" lymphocyte count is a risk factor for infection and/or severe disease; a multiancestrypolygenic risk score for lymphocytes will be tested for its prediction of COVID-19 severity to address this hypothesis. This supplemental project will improve 1) standardization of electronic health record phenotyping of the pulmonary and renal complications of COVID-19 to improve transferability across sites; and 2) our understanding of host genetic risk factors playing a role in disease severity. We propose to work within the aimsof eMERGE4 to study interindividual variability in COVID-19 severity by developing transferable EHRphenotyping of pulmonary and renal outcomes, evaluating ABO blood group association and GWAS contrasting those COVID-19 patients with respiratory failure (inpatient) with those who remained outpatients, and evaluating whether a multi-ancestry PRS for lymphocytes predicts COVID severity. This project can stand on its own, but we will gain power by pooling data across eMERGE and benefit by testing EHR phenotyping at multiple sites to assure transferability. We will also broadly share any data.",2020,2025,University Of Washington,375152,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C07118,3U01HG006379-09S1,Genomic Basis of Susceptibility to COVID-19 Infection and its Complications,"PROJECT SUMMARY In addition to causing millions of cases and hundreds of thousands of deaths, the Coronavirus disease 2019 (COVID-19) pandemic has brought life and economic activity to a near standstill in many parts of the world. A coordinated scientific effort is necessary to mitigate the widespread misery, morbidity and mortality inflicted by the pandemic. The goal of this supplemental application is to contribute to informatics and genomics efforts to identify the genomic basis of susceptibility to and complications of COVID-19. The wide spectrum of disease severity with COVID-19 is only partially explained by age and medical comorbidities and genetic factors arelikely to play a key role. Identifying genomic factors impacting COVID-19 case status and complications is important for risk stratification, identifying new pathophysiologic pathways for drug development/repurposing, and improved understanding of the biology of SARS-CoV-2 infection and its complications. As part of the electronic Medical Records and Genomics (eMERGE) since its inception in 2007, Mayo investigators have considerable experience in using the electronic health record (EHR) for genomics research. We will develop electronic phenotyping algorithms to ascertain COVID-19 case status, complications and fatality, to identify genomic variants associated with adverse outcomes. Using DNA samples linked to the EHR, we will perform genomic analyses to identify common and rare variants associated with case status, case severity and case mortality. We will collaborate with health systems and consortia in the US and around the world to increase the power and rapidity of the genomic studies. Our specific aims are: Specific Aim 1: Develop and validate electronic phenotyping algorithms to ascertain COVID-19 related phenotypes including case control status, i.e., individuals tested and those were identified to be positive for COVID-19, and disease severity, in particular cardiovascular complications including myocardial injury/infarction, arrhythmias, coagulopathy as well as large vessel thrombosis. Specific Aim 2: Perform genomic association analyses to identify variants associated with susceptibility to infection with SARS-CoV-2 and its complications. We will compare test +ve vs test -ve individuals, mild vs hospitalized cases of COVID-19 and among the latter those who develop severe disease or die. In addition to genome-wide association studies (GWAS), we will conduct association studies of the HLA region and burden tests using sequence data.",2020,2025,Mayo Clinic Rochester,282848,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2011 +C07119,3R44AG063635-02S1,DANA; A Tool to Detect Cognitive Changes in Pre-clinical and MCI Patients (Admin Supplement),"Project Summary/Abstract: The goals of this proposed project are to develop the DANA app into a tool that can be easily used remotely by COVID-19 patients after discharge from an Intensive Care Unit (ICU) and to provide clinicians with meaningful data on the immediate and long term effects of COVID-19 on a patient's cognitive function. DANA will also help clinicians optimize neurocognitive rehabilitation. DANA is an FDA-cleared neurocognitive assessment tool that has been shown to be a valid and reliable method for screening cognitive functioning and tracking changes in cognitive functioning over time. Importantly, DANA can provide results virtually through a HIPAA-compliant portal, which will protect the clinician and others from exposure to the patient. The specific aims of the proposal are: (1) technical modifications and support of DANA for in-home self-administration and remote monitoring of COVID-19 patients, and (2) deploy and show efficacious use of DANA with recovering COVID-19 patients. These will build on the specific aims of the current Phase II SBIR, which includes the same longitudinal surveillance for participants either at-risk for Alzheimer's or diagnosed with Mild Cognitive Impairment (MCI).Three control populations, composed of (1) hospitalized COVID-19 patients who do not require ICU admission, (2) post-discharge ICU patients without COVID-19, and (3) healthy participants from the Alzheimer's Disease Center Registry. All participants will be given DANA immediately before leaving the hospital to determine a baseline, then they will administer the DANA tests to themselves while they convalesce in isolation.Technical changes specific to the needs of COVID-19 patients will be made to the DANA software in order to make DANA easier to use at home and provide optimal data to the clinician.",2020,2020,Anthrotronix Inc,484753,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2019 +C07120,3U41AT008718-07S1,Urgent Covid-19 Revision to the Center for High-Throughput Functional Annotation of Natural Products,"PROJECT Summary: Viruses are cleverly dangerous; they jump from species to species, mutate to evade vaccines and single antiviral drugs, and cause many human diseases and deaths. A notorious and current example is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; hereafter abbreviated SARS-2), of which we are in the midst of a global pandemic. As we are witnessing daily, the pandemic reveals the gaping holes in the US's healthcare system and how woefully unprepared we are for viral outbreaks. While dozens of clinical trials are ongoing, we still do not yet have effective and widely available vaccines and antiviral or anti-inflammatory drugs to fight the virus and the inflammatory sequelae of infection. As such, many people have turned to natural products with the hope that these untested supplements will keep them safe and healthy. In fact, nearly 20% of the US population uses natural products for treatment or prevention of disease. The use of plant-based medicines is even more prevalent in developing countries, where for many people they constitute the primary health care modality. This COVID-19 Emergency Competitive Revision funding request to U41 AT008718-06, The Center for High-Throughput Functional Annotation of Natural Products (PIMacMillan), will address the over-riding hypothesis that natural products contain mixtures of compounds that potently inhibit SARS-2 and virus-induced inflammation primarily by targeting the cell. To address the hypothesis, the Cech, MacMillan, and Polyak labs will merge their complementary expertise in natural product biochemometrics, genetic profiling, and virology to conduct two Specific Aims that will test selected natural product extracts for suppression of virus infection using Biosafety Level (BSL) 2-compatible reporter pseudoviruses that enter cells using the SARS-2 Spike protein (Aim 1). This aim will also identify two- andthree-compound synergists consisting of mixtures of natural products and FDA approved drugs with demonstrated anti-SARS-2 and broad-spectrum antiviral activity. In Aim 2 the most potent extracts and combinations will be validated against fully infectious SARS-2 under BSL3 containment. The natural products being profiled in the U41 will be prioritized for analysis. With this approach, promising antiviral natural products or extracts will have complementary FUSION and cytological profiles such that we will gain immediate insight into mechanisms of cell engagement and action. Since natural products are well known to engage human cells to provide cytoprotection, and since many viruses engage similar pathways into and out of cells, our innovative approach and results may also work against other emerging and re-emerging infections. Thus, our practical approach will help battle COVID-19 and enhance global preparedness for the next virus outbreak.",2020,2025,University Of California-Santa Cruz,241894,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2015 +C07121,3P50HD089922-04S1,Penn State University's Translational Center for Child Maltreatment Studies TCCMS,"PROJECT SUMMARY / Abstract: Although emerging data regarding the current COVID-19 pandemic suggest that children and adolescents have a lower risk of being diagnosed with severe COVID-19 infections, serious adverse effects, including death, have been reported in this age group. Additionally, concerns that children and adolescents with mild COVID-19 infections continue to spread infections remain. Despite being less likely to be diagnosed with cases of COVID-19, youth's lives are profoundly impacted by the COVID-19 pandemic in numerous ways, including due to disrupted daily routines and educational experiences, reduced social contacts with peers and families, and, potentially, increased exposures to unsafe home environments, overwhelmed caregivers, incidents of domestic violence, and, possibly, incidents of child maltreatment. This highlights that youth with a history of child maltreatment may be particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic seeing as they are likely to come from families already experiencing multiple hardships. This impacts a large number of youth; over one third of U.S. youth are investigated for child maltreatment (CM) before theage of 18. The proposed project will build on the currently ongoing Child Health Study (CHS;HD089922, PI: Noll, Co-I: Schreier), as part of which 775 youth aged 8-13 years who were recently investigated for CM as well as 225 comparison youth without a history of CM are being recruited and followed prospectively. Taking advantage of this unique and exceptionally well-characterized cohort, we will augment the biopsychosocial data already being collected to examine vulnerability and resilience towards COVID-19 infections among these youth, as well as how the additional stress that is currently being experienced by caregivers in the study may spill over to impact youth well-being throughout and following this pandemic. We will examine whether a broad range of physiological, e.g., endocrine, immune, and metabolic, as well as psychosocial, and demographic characteristics of youth are associated with known infections of COVID-19 or with an absence of known infections in the context of having been in close contact with individuals with known infections. Additionally, we will investigate the influence of added caregiver stress on possible exacerbations of existing youth health problems, physiological markers of stress, and new incidents of child maltreatment. Thus, by shedding light on the current and future experiences of some of society's most vulnerable individuals, the resulting data have the potential to provide a powerful jumping-off point for future intervention programs to support these youth who are and will be transitioning into adulthood in the wake of theCOVID-19 pandemic. Importantly, this knowledge will also carry forward into informing responses to possible future pandemics which may have similar effects on the everyday lives of individuals.",2020,2022,Pennsylvania State University-Univ Park,160500,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease susceptibility,2017 +C07122,3DP5OD028123-02S2,"Testing Scalable, Single-Session Interventions for Adolescent Depression in the context of COVID-19","Project Summary/Abstract States and localities nationwide are taking unprecedented steps to reduce public health threats posed by COVID-19, including school closures affecting >50 million youth. The pandemic has also caused families extreme financial hardship, sudden unemployment, and distress. This combination of collective trauma, socialisolation, and economic recession drastically increases risk for adolescent major depression (MD): already thelead cause of disability in youth. However, youth MD treatments face problems of potency and accessibility. Up to 65% of youth receiving MD treatment fail to respond, partly due to MD's heterogeneity: an MD diagnosis reflects >1400 possible symptom combinations, highlighting the need for treatments matched to personal need. Treatment accessibility issues are similarly severe. Before the pandemic, < 50% of youth with MD accessed any treatment at all; newfound financial strain will further preclude families' capacity to afford care for their children. It is thus critical to identify effective, scalable strategies to buffer against youth MD in the context of COVID-19, along with strategies to match such interventions with youth most likely to benefit. This project will integrate machine learning approaches and large-scale SSI research to rapidly test potent, accessible strategies for reducing adolescent MD during COVID-19. Via the largest-ever SSI trial (N=1,200 youth with elevated MD symptoms, ages 12-16), Aim 1 is to test whether (1) evidence-based SSIs improve proximal targets (e.g., hopelessness and perceived agency, which has predicted longer-term SSI response) and 3-month clinical outcomes (MD severity) during the COVID-19 pandemic, and (2) whether SSIs targeting cognitive versus behavioral MD symptoms are most impactful in this context. In a fully-online trial, youths recruited from across the U.S. will be randomized to 1 of 3 self-administered SSIs: a behavioral activation SSI,targeting behavioral MD symptoms (anhedonia; activity withdrawal); an SSI teaching growth mindset, the belief that personal traits are malleable, targeting cognitive MD symptoms (e.g. hopelessness); or a control SSI. Per baseline, post-SSI, and 3-month follow-up data, we will test each SSI's relative benefits, versus the control, in the context of COVID-19. Results will reveal whether SSIs targeting behavioral versus cognitive symptoms differentially reduce overall MD severity in this context. Aim 2 is to test whether (and, if so, which of) SSIs can impact COVID-19 specific trauma and anxiety symptoms, informing whether novel, COVID-19-tailored supports may be needed to reduce pandemic-specific mental health sequelae. Aim 3 is to test person-level and contextual predictors of SSI response, via machine-learning techniques, regardless of overall intervention effects observed. Given MD's heterogeneity, we will test whether baseline symptoms (e.g., having more severe cognitive or behavioral MD symptoms) predict response to SSIs targeting different symptom types. We will also test exposure to COVID-19-related adversities (e.g. parent job loss; loved one hospitalized for COVID-19) and general disadvantage (e.g. family low-income; racial minority status) forecast SSI response.",2020,2021,Stony Brook University,392813,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2019 +C07123,3UG1CA189960-07S1,Columbia University Minority/Underserved Site NCI Community Oncology Research Program,"Cancer patients are at particular risk for COVID-19 infection and adverse outcomes associated with the disease. A nationwide cohort study of over 1000 cancer patients diagnosed with COVID-19 reported a 13% mortality rate due to complications, dramatically higher than that seen in subjects without cancer. In addition to the direct impact of COVID-19 infection in cancer patients, the COVID-19 pandemic has resulted in a reallocation of hospital and medical resources to the care of patients with COVID-19. This resource strain has resulted in delays and discontinuation of treatments for chronic diseases such as cancer. Delays and interruptions in chemotherapy, radiotherapy and surgery are common among cancer patients. Our preliminary data strongly suggests that minority and socioeconomically disadvantaged cancer patients are at particular risk for interruptions in their cancer care. The overarching goal of this proposal is to determine the interplay of race and neighborhood socioeconomic factors on cancer care delivery for oncology patients during a period of wide community spread of COVID-19. We will utilize large scale datasets to analyze factors associated with COVID19 infection among a racial and socioeconomically diverse group of cancer patients and perform quantitative surveys in this population to determine how COVID-19 has impacted receipt of cancer care and enrollment onto clinical trials. Specifically, we will link data from 2,000 patients with cancer diagnosed between December 3, 2019 and August 1, 2020 and receiving cancer treatment at Columbia University Irving Medical Center in New York City to census and real estate tax assessment data to determine the association between race and neighborhood socioeconomic status and COVID-19 infection rates. We will then survey a diverse subset of these cancer patients (n = 150, 75 non-Hispanic whites and 75 Hispanic and black) to quantitatively assess knowledge of, attitudes toward, and behaviors related to SARS-CoV-2 and determine how community social and economic indicators, stress, coping style and social support have influenced cancer treatment delays and clinical trial participation during the COVID-19 pandemic. We hypothesize that minority cancer patients and those residing in neighborhoods with low socioeconomic status are increased risk for COVID-19 infection and are more likely to experience treatment delays and disruptions of their cancer care and clinical trial participation. The proposed work will comprehensively determine how racial and socioeconomic factors influence COVID-19 infection and care delivery among cancer patients. We will leverage our unique population of racial and socioeconomically diverse patients from a cancer center at the epicenter of COVID-19 infection in New York City. We anticipate that data from these studies will identify demographic factors associated with a particularly high risk for COVID19 infection and cancer treatment alterations that may impact survival. Ultimately, these data will be utilized to develop pragmatic interventions to help reduce the burden of COVID-19 on cancer care in vulnerable and minority populations.",2020,2025,Columbia University Health Sciences,162000,Human Populations,Black | White | Other | Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Disease susceptibility | Supportive care, processes of care and management | Communication | Indirect health impacts | Other secondary impacts",2014 +C07124,3R01AG061514-02S2,Nicotinamide riboside supplementation for treating elevated systolic blood pressure and arterial stiffness in middle-aged and older adults,"PROJECT SUMMARY/ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 that causes Coronavirus Disease 2019 (COVID-19) disproportionately affects older adults such that individuals 60 years and older have markedly increased risk of infection, severity of morbidity, and mortality. This increased vulnerability with aging is due inpart to greater systemic inflammation and oxidative stress, impaired nitric oxide (NO)-mediated endothelial dysfunction, and nicotinamide adenine dinucleotide (NAD+) deficiency both at baseline and post-infection. As such, novel ""geroprotective strategies"" that: 1) improve baseline risk factor profile for COVID-19; and 2) restore NAD+ levels, inhibit inflammation and oxidative stress, and improve NO bioavailability/endothelial dysfunction induced during infection, are essential for reducing severity/lethality of COVID-19 in older adults. We recently showed that chronic supplementation (6 weeks) with nicotinamide riboside, a natural dietary compound, boosts NAD+ bioavailability in older adults. We then translated the results of this pilot study into an NIA-funded (R01 AG061514) phase IIa randomized clinical trial assessing the efficacy of 3 months of nicotinamide riboside treatment for lowering systolic blood pressure (SBP) and aortic stiffness in older adults with baseline SBP in the elevated to stage 1 hypertension range. This 5-year clinical trial is currently in year 2. The pathogenesis of COVID-19 includes NAD+ deficiency, hyper-inflammation, excessive reactive oxygen species (ROS) bioactivity, and pulmonary and systemic NO-mediated endothelial dysfunction. Our preliminar yresults in older adults suggest that nicotinamide riboside reduces pro-inflammatory cytokine production in peripheral blood mononuclear cells (PBMC), decreases endothelial ROS bioactivity, increases endothelial NO production, and improves in vivo systemic vascular endothelial function. However, these promising initialfindings must be confirmed in a larger cohort to establish the potential efficacy of nicotinamide riboside supplementation as a geroprotective strategy for prevention and treatment of COVID-19 in older adults. The purpose of this administrative supplement is to address a major research objective for the NIADivision of Geriatrics and Clinical Gerontology in NOT-AG-20-022: The evaluation of pharmacological interventions that may prevent or mitigate morbidity and/or improve post-infection health in older adults exposed to SARS-CoV-2. This will be accomplished by: 1) assessing PBMC inflammatory cytokine production before/after nicotinamide riboside treatment and incubation with specific NAD+-pathway metabolites; 2) evaluating ex vivo endothelial function in human pulmonary artery endothelial cells bathed in subject serum with/without COVID-19-like inflammatory and oxidative stress ± protective NAD+ metabolites; and 3) assessing in vivo systemic endothelial function with nicotinamide riboside treatment. The expected results will establish nicotinamide riboside as a promising geroprotective strategy for: a) reducing risk of SARS-CoV-2 infection; b) inhibiting multiple pathways driving COVID-19 morbidity; and c) aiding post-infection recovery in older adults.",2020,2023,University Of Colorado,571966,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2019 +C07125,3R01AG054131-04S1,"Trial of GlyNAC in Older Adults with COVID-19: Glutathione, Inflammation and Recovery","The global pandemic caused by the novel Coronavirus SARS-Cov-2 results in COVID-19 and is associated with a very high mortality rate ranging from 3% (in USA) to 14% (in Italy) Increased age is identified as a high-risk group for COVID-19due to significantly high mortality in older adults (OA). It is not clear why COVID-19 is associated with high mortality, but emerging evidence from hospitalized patients has identified a `cytokine storm' with severely elevated inflammatory cytokines (especially IL-6) as a potential contributor. Increased inflammation in patients with COVID-19 is reported to correlate negatively with peripheral lymphocyte populations, and contributes to immune dysfunction. We have studied aging for >20 years, and found that correcting the deficiency of the endogenous antioxidant protein glutathione (GSH) is critically important to lower inflammation, elevated oxidative stress (OxS) and impaired mitochondrial fatty-acid oxidation (MFO)in OA. GSH is the most abundant endogenous, intracellular, antioxidant protein and functions by protecting cells from toxic OxS generated during mitochondrial energy production. OA are deficient in GSH. We have identified and validated an effective, simple and safe nutritional intervention called GlyNAC (combination of GSH precursors glycine and NAC-N-acetylcysteine) to correct GSH deficiency in OA. GSH is identified as a potential candidate to combat COVID-19, but has not been studied in OA with COVID-19.We recently completed a 16-week NIH-funded double-blind placebo-controlled randomized clinical trial in OA with outcomes measured at 2-weeks and 16-weeks. GlyNAC supplementation for 14-days led to: (1) RBC-GSH ­40%; (2) lowered inflammation; (3) lower OxS; (4) improved mitochondrial function.In earlier pilot studies in OA we found that: (1) OA had striking GSH deficiency, elevated OxS and impaired MFO; (2) GSH deficiency in OA occurs due to diminished synthesis, caused by decreased availability of its precursor amino-acids glycine and cysteine, and can be improved by supplementing GlyNAC for 14-days [; (3) GlyNAC supplementation improved inflammation, OxS , MFO, cognition and function.These results are highly relevant to OA with COVID-19 because: (1) OA with COVID-19 have a high mortality risk; (2) increased inflammation is associated with high mortality in COVID-19; (3) GSH is identified as a potential candidate tocombat COVID-19; (4) OA have GSH deficiency, chronic inflammation and cognitive impairment and GlyNAC corrects these defects in OA; (5) GlyNAC has a strong safety profile in our trials; (6) GlyNAC, GSH and OxS have not been studiedin COVID-19. (7) GSH prevents replication of the influenza virus in rodents. Based on these data, we propose an exploratory pilot randomized clinical trial to test the effect of supplementing GlyNACvs. placebo for 14-days in hospitalized in OA with COVID-19 to determine the impact on clinical improvement, recovery,survival, cognition, function, inflammation, immune and mitochondrial function, GSH concentrations and oxidative stress.If successful, this could identify GlyNAC as a novel nutritional supplement to improve the health of patients with COVID.",2020,2022,Baylor College Of Medicine,520848,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2017 +C07126,3P01AG051428-05S1,Downstream sample analyses from 3 NHP species infected with SARS-CoV-2.,"Over the last three months, COVID-19 has emerged as a major pandemic. Coronavirus SARS-CoV-2, the causative agent of COVID-19, has remarkable infectiousness and pathogenicity, particularly in the elderly and people with immunocompromising conditions.1 The CDC have reported that 8 out of 10 deaths reported in the US related to COVID-19 are in adults 65 years and older. Similar to many other pulmonaryinfectious diseases, the elderly can present with atypical symptoms and initial signs of SARS-CoV-2 infection may be missed resulting in ongoing infection transmission. Texas Biomed recently infected two different age groups of common marmoset, rhesus macaque and baboon with SARS-CoV-2. Each species had differing infection outcomes. Extensive sample collection occurred throughout the 14-day study, providing an array of banked samples from 3 species of NHP, two age groups, and infected and non infected controls. We propose five Aims using banked samples, to increase our understanding of SARS-CoV-2 infection and the host response in old age. Aim 1 will investigate whether the pulmonary environment during SARS-CoV-2 infection results in oxidation of host innate molecules and a possible link to COVID-19 Acute Respiratory Distress Syndrome (CARDS). Aim 2 will determine the phenotype and function of resident and infiltrating innate immune cells during SARS-CoV-2 infection with a focus on the initiation and maintenance of a cytokine storm. Aim 3 will dissect the Tand B cell response in lung and lymph nodes during early SARS-CoV-2 infection that may lead to relevant information about long term protective immunity. Aim 4 will focus on the virus during infection, determining whether viral mutations occur and whether they differ between species and age. Aim 5 will support in-depth analyses of formalin fixed tissues with a goal of viewing SARS-CoV-2 infection beyond the lung and identifying correlates of infection progression in organs such as the brain, heart and intestine.",2020,2021,Texas Biomedical Research Institute,1179314,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2016 +C07127,3U01HG011169-01S1,Northwestern Genomic Risk Assessment and Management Program,"PROJECT Summary: Since early 2020, COVID-19 disease spread rapidly across the US and will likely be sustained or recur periodically until an effective vaccine or prophylactic treatment is developed. The pandemic will have a large impact on the conduct of the next phase of eMERGE, including recruitment of new participants as well as development, validation, and implementation of genomic risk assessments based on polygenic risk scores (PRS). The supplement presents an opportunity for Northwestern to contribute eMERGE network efforts to promote the understanding of the genetic epidemiology and individual susceptibility to COVID-19 infection, disease severity, and complications. In support of efforts proposed in the supplement application for the coordinating center, we propose to expand Aim 1 of our eMERGE 4 application with the following aim: Create,validate and implement COVID-19 ePhenotyping for manifest disease, disease severity, and specific COVID-19 complications in the Northwestern biobank. Recognizing that decisions about ePhenotypedevelopment and implementation will be made in collaboration with the coordinating center and other participating eMERGE 4 sites, in this supplement, we propose leading phenotype development of three critical COVID-19 phenotypes 1) myocarditis, 2) acute kidney injury, and 3) coagulopathy complications. Additionally,we propose to facilitate studies of the full spectrum of COVID-19 disease including those with minimal or no symptoms, which will motivate participation in eMERGE 4 among individuals who may have been at higher risk to exposure to COVID-19. To achieve this, we will expand aim 2 of our parent eMERGE 4 application with the following 2 aims: a) provide SARS-CoV-2 serological testing for IgG to all Northwestern participants recruited into eMERGE 4 in year 1 of the award and b) facilitate SARS-CoV-2 serology testing and genotyping of cohabitating family members of eMERGE 4 participants by mail.",2020,2025,Northwestern University At Chicago,384018,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity | Disease pathogenesis",2020 +C07128,3R01DA042069-04S1,Health outcomes and cognitive effects of marijuana use among persons living with HIV/AIDS,"Abstract: Persons living with HIV (PLWH) are an especially vulnerable population in the COVID-19 pandemic given their compromised immune system and comorbidities (e.g., substance use, mental health issues). Currently, no research has examined how the broad impacts of COVID-19 (e.g., extended social isolation, anxiety, familyloss) are affecting marijuana use, cannabis use disorder (CUD), and care engagement in PLWH. Further, research has not clarified whether chronic marijuana use will interact with HIV infection to impact the onset and progression of COVID-19 infection. This urgent supplement will allow us to capture this window of opportunity and collect timely data to address these gaps. Our ongoing R01 study of a PLWH cohort focusing on marijuana use provides many unique strengths to support this supplement. The primary goal of the active R01project is to examine the long-term impact of marijuana use on cognitive functioning and health outcomes in a cohort of PLWH (currently 300 participants completed baseline assessment) in Florida. This supplement is within the scope of the parent grant but extends the parent study by incorporating COVID-19-related questions/measures into the ongoing data collection. We will collect additional data using a mixed method approach which includes quantitative survey questions and in-depth qualitative interviews on a selected subsample. We will conduct COVID-19 antibody tests using the blood sample we collect as a part of the parent grant procedures. We will also link the collected data with the Florida Department of Health EHARSdata on HIV-related outcomes (e.g., viral load) over time, which is also a part of the parent study. The specific aims of this supplement include: 1) To identify the impact of the COVID-19 pandemic on changes in marijuana use and cannabis use disorder (CUD) among PLWH; 2) To determine the impact of the COVID-19 pandemic on the HIV care continuum (i.e., HIV care engagement) and outcomes (i.e., viral load); and 3) To estimate the prevalence of COVID-19 infection in our study sample after September 2020, using antibody testing for IgG and IgM. If we have a large enough sample (i.e., 10% tested positive for COVID-19), we will examine the association between marijuana use status and COVID-19 incidence/severity. This study will be the first to address the impacts of the COVID-19 pandemic among an ongoing cohort of PLWH with a focus on marijuana use and its related health outcomes. By collecting additional COVID-19-related information as a part of the regular follow-ups in the parent study, we will be able to provide valuable evidence on how the COVID-19 pandemic may cause changes in PLWH's marijuana use/CUD and HIV care/outcomes and will be able to identify the underlying mechanism of these changes. Results from the antibody tests may also provide informative data on whether marijuana use interacts with HIV in affecting COVID-19 incidence and severity,which can potentially inform future prevention and treatment programs for COVID-19 in this population.",2020,2022,University Of Florida,148760,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2017 +C07129,3R01HG010092-04S1,Admin. Supplement to: Ensuring Patients' Informed Access to Noninvasive Prenatal Testing,"PROJECT Abstract: Prenatal genetic screening tests and diagnostic tests (referred to as prenatal genetic tests) are a fundamental component of the delivery of high-quality, evidence-based prenatal care. Current guidelines recommend that prenatal genetic tests should be offered to all pregnant patients to optimize obstetric outcomes, ideally offered early in pregnancy so that patients can make formative decisions about their prenatal care. Delay in access and utilization of prenatal genetic tests can have significant implications for pregnancy outcomes. The COVID-19 pandemic is an urgent clinical problem that has emerged with the potential to jeopardize women's access to genetic tests. Currently, it is not known how COVID-19 may impact pregnant women's access to and utilization of these critical tests. This includes concern not just for those pregnant women who become severely ill with COVID-19 but also those who fear exposure to SARS-CoV-2 by presenting to a healthcare facility have genetic testing by means of a blood draw or ultrasound-based procedure. The goal of this study is to study the effect of COVID-19 on prenatal healthcare delivery, specifically patients' ability to access prenatal genetic screen-ing and diagnostic tests in an informed and evidence-based fashion. By doing so, we will identify serious short term health issues for women, children, and families resulting from this pandemic and readily-deployable and scalable solutions to ensure women's informed access to high-quality prenatal care during future public health crises. This study is significant as its findings will lead to system-level improvements to support pregnant patients' informed access to prenatal genetic tests for the duration of the pandemic and future public health emergencies of similar magnitude. Additionally, this study will increase the impact of theNEST R01, providing an in-depth understanding of how COVID-19 affects shared decision-making, informed consent, and patient satisfaction regarding prenatal genetic testing decisions. In doing so, this proposal dove-tails with the objectives of the parent R01 to ensure that patients have informed access to advances in prenatal genetic technologies as crucial metrics of prenatal healthcare safety, access, and quality.",2020,2021,Cleveland Clinic Lerner Com-Cwru,223677,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health service delivery",2017 +C07130,1R01AI157827-01,Point-of-Care RT-PCR System to Inform COVID-19 and Respiratory Illness Decisions,"Project Summary The ongoing COVID-19/SARS-CoV-2 pandemic highlights the need for simple, rapid, and cost-effective testing for respiratory infections at the point-of-care, including physician's offices, urgent-care settings, ambulatory procedural centers, and low-resource environments. The need is particularly notable for respiratory infections, such as COVID-19 and influenza, which can present with similar symptoms yet require distinct management strategies. With its high sensitivity and specificity, RT-PCR is the gold standard for the molecular diagnosis and differentiation among respiratory pathogens. Traditional RT-PCR workflow requires significant control over specimen contents and reaction conditions, with current methods requiring nucleic acid extraction prior to amplification and detection. The net result is increased complexity, cost, and/or turnaround time for diagnosis. In this context, we have observed in recent influenza studies that outstanding analytic performance characteristics can be achieved without RNA extraction, by applying our novel workflow and Adaptive PCR technology. Unlike traditional RT-PCR, Adaptive RT-PCR incorporates mirror-image L-DNA enantiomers-identical in sequence to PCR primers and targets-that modify cycling conditions to match the biochemical sample contents, thus eliminating the need to monitor reaction temperature. The direct monitoring of reaction conditions overcomes many of the limitations of traditional PCR, facilitating direct amplification within the original specimen matrix, simplifying instrument design, and enabling single-tube analyses. SARS-CoV-2 and influenza are both enveloped RNA viruses, with specimens collected in the same manner (i.e. nasopharyngeal swab) and using the same viral transport medium. Therefore, we hypothesize that we may eliminate RNA extraction for this virus, like we have done for influenza, by performing Adaptive RT-PCR directly on clinical specimens. We propose to enable a simplified methodology through Adaptive RT-PCR, creating diagnostics for COVID-19 and other respiratory pathogens without RNA extraction. As a collaboration between biomedical engineers and a COVID-19 diagnostic laboratory, we seek to develop a workflow and instrument that are simple-to-use, cost-effective, and suitable for point-of-care settings, tools that can rapidly inform treatment and management strategies. To achieve this goal, Aim 1 will evaluate the performance of RT-PCR directly - that is, without RNA extraction - using both traditional and Adaptive RT-PCR instrumentation. Aim 2 will develop multiplexed amplification reagents to create a sensitive and specific respiratory panel thatdetects SARS-CoV-2, four other viruses, two bacteria, and one control target. Ultimately, Aim 3 will design andfabricate a self-contained Adaptive RT-PCR instrument suitable for point-of-care settings, while validating this system using characterized human specimens in a CLIA-accredited lab environment. Completion of this project will result in a novel point-of-care tool for both the established and emerging respiratory infections that threaten public health, facilitating rapid treatment, follow-up, infection prevention, and epidemiologic containment.",2020,2025,Vanderbilt University,791662,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07131,3UH3DA044826-04S1,"Community-based, client-centered prevention homes to address the rural opioid epidemic","PROJECT SUMMARY In response to NOT-DA-20-047, Notice of Special Interest (NOSI) regarding the Availability of AdministrativeSupplements and Urgent Competitive Revisions for Research on the 2019 Novel Coronavirus, our research team proposes increase our understanding of drug use and syringe sharing behaviors, overdose, impacts of homelessness, and other potential barriers PWID face during COVID-19 by developing a phone based survey among PWID who participated in the first phase of the Wisconsin Rural Opioid Initiative. The survey will be embedded in our proposed virtual intervention adapted from our original proposal. Last, we will evaluate how restricted operations at the SSP changed utilization of syringe services and assess the feasibility of the use of at-home HIV and viral hepatitis testing and counseling by phone Using the organizational infrastructure of our local SSP, Vivent Health, a geographically disperse population of people who inject drugs in rural communities across Northern Wisconsin, we are building locally responsive systems to facilitate uptake of evidence-based prevention services for high-risk clients. Understanding information on how COVID-19 may change risk is needed to provide effective prevention and treatment to PWID. The growing problem of opioid injection in rural Wisconsin is highly significant because it exemplifies trends observed nationally indicating severe vulnerability to worsening epidemics of HIV, HCV, and opioid overdose deaths in rural communities that are substantially underserved by evidence-based prevention interventions.This proposal is highly innovative because it will enable us to use an evidence-based intervention in a unique way to reach clients during a global pandemic. Additionally, we have the ability to assess how the pandemicwill have long-term effects on people who inject drugs that will inform future interventions. It has potential for high impact because of our team's state-wide reach, broad access to at-risk individuals, and robust infrastructure for conducting a rigorous, multi-site evaluation of our proposed model.",2020,2022,University Of Wisconsin-Madison,127201,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2017 +C07132,3U24OD026629-04S1,Stanford MoTrPAC Bioinformatics Center,"Abstract: Control of SARS-CoV-2 infection and related pathogenic processes requires an understanding of how host and viral genetics factors drive disease outcome. The study is designed to characterize the genomic epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) and define host genetic effects on the outcome of viral infection. We will whole-genome sequence 1,000 COVID-19 positive patients at Stanford Health Care as part of this research study. Stanford University Hospitals and Clinics has piloted a robust and reproducible next-generation sequencing assay for joint viral and host genome detection. An initial pilot of 319 nasal swab samples and 15 Buffy coats from ICU patients demonstrates we are able to extract, sequence and analyze low pass host genomes and RNA seq data on all nasal swabs. Of these swabs,we were able to obtain full viral genome sequences from 180. Genetic ancestry analysis of the 319 host genomes shows overrepresentation of Hispanic/Latinos, Pacific Islanders, and other at-risk populations, recapitulating the ethnic disparity we and others have seen among cases. In this project, we will sequence additional samples to bring our total to 1,000 COVID-19 positive samples including inpatient, outpatient, severe, and critically ill patients. We will scale this project over the next 12 months and follow infected, severe,critical, and recovered patients to characterize the multiomic profile of disease severity from mild to severe to critically ill. This will be accomplished through two Aims. The first aim focuses on host genetic sequencing from NP swabs where we expect to recover sufficient genetic material to characterize the host genome to high imputation quality. We will also characterize host genetic ancestry and background polygenic risk score for ahost of related traits. A set of 100 contemporaneous COVID-19 negative samples will also be sequenced as controls and comparison for background ancestry in the treatment population. In parallel we will collect DTC derived genetic data from a diverse population sample. Our second aim focuses on the virus genome data obtained from NP swabs. We will fully characterize as much of the SARS-CoV-2 genome per sample as possible and detect co-infections in the swab sample. Our goal is to understand the limit of detection for the technology, impact on reproducing viral dynamics, and characterizing alternative splicing in the SARS-CoV-2 genome over the time course of infection. Completion of the Aims outlined here will pilot Next Generation Sequencing for surveillance of SARS-CoV-2 host and viral genetics in Northern California that can be replicated across the world. This is critical for preparedness of a second wave and detecting co-infections among those infected with SARS-CoV-2 and contributes significantly to the emergency tracking of the pandemic during the second half of 2020 and beyond.",2020,2022,Stanford University,665425,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2016 +C07133,3UL1TR002243-04S4,Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasma,"The Vanderbilt Institute for Clinical and Translational Research (VICTR) is a highly functional and integrated clinical and translational (C&T) research infrastructure that has raised the quality and scientific rigor of the research conducted at Vanderbilt and longstanding partner Meharry, the nation's oldest historically black academic health science institution. VICTR will contribute to the mission of the CTSA program while leveraging unique resources and expertise within VICTR's Hub with these aims: 1) Leverage VICTR's strong collaborative energy to enhance team science methodologies that propel transdisciplinary research approaches, and integrate proven community engagement principles to stakeholders for all stages of research; 2) Develop,implement and disseminate informatics and data organization methods to promulgate research efficiency, quality, and preparedness and integrate data collection in the conduct of pragmatic trials; 3) Ensure the translational science workforce is diverse and has the skills, knowledge,and resources necessary to advance translation of discoveries; 4) Measurably improve theefficiency, quality, and representativeness of C&T studies by enhancing and systematically integrating services and programs that support highest quality research initiation and conduct; 5) Measurably improve the efficiency and quality of multi-site clinical trials, in collaboration with the TICs and RICs, by leveraging centralized regulatory and legal agreements, providing rapid feasibility and recruitment methods and practices, and creating and disseminating novel clinical trial designs and methodologies; and 6) Utilize unique strengths leveraging novel resources BioVU and PheWAS to guide drug development and repurposing.",2020,2022,Vanderbilt University Medical Center,562991,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +C07134,3UH3MH114249-04S1,Mechanisms underlying resilience to neighborhood disadvantage (Administrative Supplement),"Summary: Decades of research have confirmed the damaging effects of chronic and acute adversities on socioemotional, academic, and health outcomes [1-10]. And yet, many children growing up in these contexts demonstrate`resilient' outcomes (operationalized here as both the presence of adaptive competence(s) and the absence of psychopathology). How do children achieve such adaptive outcomes in the face of significant adversity? Extant studies indicate that protective familial- and community-level factors promote socioemotional resilience by buffering children from the effects of adversity [11-16]. Very little work, however, has considered the neurobehavioral pathways through which these protective processes confer resilience [17]. The parent grant will do just this in a sample of youth residing in neighborhood disadvantage, identifying neural markers of resilience to chronic adversity and illuminating the multilevel etiologic processes through which protective factors promote these neuro-resilient pathways. The proposed supplement will enhance this work, leveraging anatural experiment with an exogenous and acute stressor (COVID-19 and its economic, social, and personal impacts) to illuminate the ways in which protective factors promote neuro-resilience to acute adversity as well. We propose to reassess all twin families eligible for the parent grant (i.e., early-to-mid adolescent twin pairs residing in modestly-to-severely disadvantaged neighborhood contexts across lower Michigan), conducting two online COVID-19 related assessments across the next year. We will specifically collect data on the economic, occupational, health, and social impacts of the pandemic and their downstream mental health consequences (e.g., depression, anxiety), as well as youth adaptive competencies in the face of COVID-19. In this way, we can evaluate how the impacts of business and school closures unfold over the course of the pandemic, as well as whether and how some youth developed resilience to these significant stressors. By leveraging exposure to an exogenous and acute stressor like COVID-19, the proposed supplement will allow the parent grant to expand its current focus on neuro-resilience to chronic adversity to also include an acute stressor as well.",2020,2022,Michigan State University,156365,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2017 +C07135,3R35CA232097-04S1,TOWARDS PRECISION IMMUNO-ONCOLOGY: UNRAVELING THE GENOMIC DETERMINANTS AND MECHANISMS UNDERLYING IMMUNOTHERAPY EFFICACY AND RESISTANCE,"The SARS-CoV2 virus has caused a worldwide pandemic resulting in a great deal of morbidity and many deaths. Infection with this virus causes the COVID-19 disease, which can result in acute respiratory distress syndrome. Even in patients that survive the disease, the virus can cause significant morbidity, require ventilator support for respiratory functions, and necessitate a prolonged recovery process. Interestingly, severe sequelae of COVID-19 is not uniformly distributed across the population. While some people are asymptomatic or have mild symptoms, others can rapidly succumb to the disease. Some early data have been generated that shows that cancer patients may be particularly harmed by SARS-CoV2 infection 7,8. However, the differential effects of the infection on patients with different cancers and how genetic factors influence outcomes is unknown. The overall goal of the work proposed in this supplement is to characterize the effects of critical genetic variables on COVID-19 prognosis in cancer patients. The central hypothesis of this proposal is that specific genetic features - HLA genotype and distinct somatic mutations - can strongly influence the severity of COVID19 infection. We will pursue 2 specific aims. In Aim 1, we will elucidate the effects of HLA diversity on prognosis and severity of COVID19 infection in cancer patients. Based on our preliminary data, the working hypothesis here is that HLA molecular diversity will affect prognosis in COVID19 patients with advanced cancers. We have previously developed a highly versatile method to quantitate HLA diversity called HLA evolutionary diversity (HED). We will characterize the effects of HED and HLA allelic effects on COVID severity in cancer patients. In Aim 2, we will characterize the effects of immunologically active driver mutations in cancer patients with common tumors. It is well known that certain driver genes can affect both the tumor immune environment as well as systemic immunity commonly through cytokine dysregulation. Our hypothesis here is that immunologically active cancer drivers may affect COVID19 clinical course. Using our large cohorts of cancer patients with clinical sequencing available, we will examine the effects of common somatic driver mutations on COVID19 prognosis. The combination of our aims will provide novel and impactful insights into the effects of genetic determinants on the clinical course of cancer patients who contract COVID19",2020,2025,Cleveland Clinic Lerner Com-Cwru,161000,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C07136,3U54MD007600-34S1,Center for Collaborative Research in Minority Health and Health Disparities (1),"PROJECT SUMMARY /Abstract: According to literature pregnant women are at a greater risk for exposure and death during emergencies. The overall purpose of this proposed study will be to assess and describe how the isolation and physical distancing measures related to the current Coronavirus pandemic have affected pregnant women and mothers of children 12 months or younger in Puerto Rico. The specific aims of the proposed project are: 1) Examine the impact of the COVID-19 outbreak in pregnancy related experiences and outcomes; 2) Examine the mental health impact of the COVID-19 outbreak in pregnant women and mothers of children 12 months or younger; and 3) Identify risk and protective factors of pregnant women and mothers of children 12 months or younger in the COVID-19 outbreak. Participants will be recruited from the Puerto Rico Test-site for Exploring Contamination Threats (PROTECT) consortium cohort which is composed of pregnant women and mothers from the northwestern region of Puerto Rico that studies the effects of exposure to contaminants and preterm birth and other birth outcomes. The research will have two-phased mixed methods approach with an online-based quantitative survey and a series of individual semi-structured qualitative interviews. Results from the study will provide anassessment of the COVID-19 impact on pregnancy outcomes, mental health status as well as identify risk and protective individual and contextual factors among pregnant women and mothers of children 12 months or younger. The study findings will provide greater insight into the experiences and needs of Latino Hispanic pregnant women and mothers of children 12 months or younger during pandemics. We expect that the findings can lead to the development of interventions for community health centers around the island and also to the creation of evidence-based protocols aimed at the Puerto Rican population.",2020,2022,University of Puerto Rico Medical Sciences Campus,105757,Human Populations,Other,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,1997 +C07137,3R43MD014916-01S1,Digital contact tracing and case investigation application on the Navajo Nation,"PROJECT Summary: The COVID-19 pandemic has had a disproportionate effect on the Navajo Nation, in which there is a higher prevalence of health complications such as diabetes, heart and lung disease. Overall living conditions and a long history of inequities resulting in a distrust of western medicine and health systems are believed to contribute to the spread of the virus. This project is an urgent competitive revision to an existing project in response to PA-18-935. The project supplements an ongoing SBIR Phase I project to study the feasibility and acceptability of COPECare, a novel digital system to support care coordination on the Navajo Nation, particularly those who have or are at high risk of cancer. COPECare is designed to facilitate the work of community health representatives (CHRs) who play a critical role in delivering health education and guidance to members of the Navajo Nation. Since the outbreak of COVID-19 on the Navajo Nation, CHRs and other trained and lay workers have been tasked to support contact tracing efforts throughout the community using a digital contact tracing and case investigation tool. The goal of this urgent supplement is to study the process and early outcomes of a digital contact tracing and case investigation tool that was customized for use on the Navajo Nation and rapidly deployed to support efforts to manage and control the COVID-19 outbreak. We will address this goal in the following two specific aims: In Aim 1, we will evaluate the digital tool using key metrics to gauge program performance for case interviewing and measures of system efficiency. In Aim 2, we will conduct a formative assessment consisting of qualitative one-on-one and group interviews with cadres of contact tracers (CHRs,public health officials, and hospital staff at two large hospitals serving the Navajo Nation) and cancer survivors and their families directly or indirectly affected by COVID-19. Results of this supplement work will directly inform the design and development of COPECare and contribute to a broader understanding of how to develop effective community-based digital solutions to support and promote health on Navajo Nation and potentially other tribal communities across the US.",2020,2021,Dimagi Inc,181240,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Approaches to public health interventions | Restriction measures to prevent secondary transmission in communities | Community engagement,2019 +C07138,1U01CA260539-01,Early Drivers of Humoral Immunity to SARS-CoV-2 Infections,"The duration and nature of humoral immunity to SARS-CoV-2 (CoV2) infection is poorly understood. Most studies have focused on the immune response in patients with clinical illness, but little is known about antibody response to CoV2 regarding the earliest immunological events immediately after exposure and prior to onset of illness or in asymptomatic individuals and how this impacts long-term immunological memory. This proposal addresses these gaps in our knowledge by prospectively following household contacts with clinical cases of CoV2 to determine innate and adaptive immune events associated with this early viral exposure over a 28 day period. Detailed evaluation of samples from these patients including RNAseq of peripheral blood cells and proteomic analysis of oral secretions, the site of initial CoV2 replication. We will determine whether potentially cross-reactive T cells and secretory IgA may contribute to this early protective immune response and if present do they enhance the subsequent humoral immune responses by providing greater T cell help to B cells. These studies will also provide a detailed knowledge of innate immune responses to CoV2 and how this shapes the nature and duration humoral immunity. Our central hypothesis is that peripheral blood lymphocytes and or opharyngeal secretions collected from individuals at the time of viral exposure and prior to onset of symptoms will show innate and adaptive immune responses that correlate with viral clearance and predict whether or not effective humoral immunity and long-term immunological memory develops. This hypothesis will be addressed by exploring the following aims; i) evaluating the early immune humoral and cellular immune responses to CoV2 in close contacts of individuals diagnosed with COVID-19; ii) to assess early innate immune responses in close contacts of individuals diagnosed with COVID-19 and assess their relationship with humoral immune responses and viremia; and iii) to examine early drivers of humoral immunity on the durability of immunological memory and responses to vaccines. This comprehensive evaluation of the relationships between early infection with innate and adaptive immune on long-term memory and immunity will provide a rigorous basis for the development of highly informative and scalable serological tests. Our approach is therefore highly responsive to RFA-CA-20-039, through the development and validation of novel assays that simultaneously measure innate and adaptive immune responses to CoV2 from early infection; this approach will help define immune parameters and serological markers associated with asymptomatic vs. symptomatic infection and disease severity.",2020,2022,Case Western Reserve University,1364482,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07139,3R44CA200174-04S1,Improved diagnostic sensitivity for rapid COVID-19 testing using Enhanced Preservation Media,"Project Summary COVID-19 continues to be a global emergency. As nations and economies attempt to reopen, therate of viral spread and deaths continues to rise, particularly in many large urban centers withinthe United States, where shelter in place orders did not sufficiently reduce infection burden.Continued improvement in SARS-CoV-2 testing infrastructure and test performance are urgently needed. False negative testing rates have been reported at 30-50%, meaning that for every 10 COVID-19 positive patients tested, 3 to 5 will receive an inaccurate negative result. These false negative rates occur with all testing platforms currently used, making control of viral spread nearly impossible. While the technology underlying the test systems themselves are technically very sensitive, much of the lost sensitivity arises earlier in the test process during sample collection, transportation, and RNA extraction. Global rates of high false negative test results - using the best test kits and protocols -continue to arise from two major sources: First, samples are not well preserved in CDC endorsed Viral Transport Media/Universal Transport Media (VTM/UTM) or other transport medias, leading to a 10-100x signal loss as a consequence of poor preservation; Second, the remaining sample is then further diluted often to 0.25% of the original concentration during extraction before going into the test. Until these fundamental testing problems are solved, and with no other solutions available, high false negative test results will allow viral spread to continue rising. In order to address this unmet need, Convergent Genomics has developed Enhanced PreservationMedia™, a universal specimen transportation and integrated extraction solution, to significantly improve testing performance. Enhanced Preservation Media (EPM) enables the following testing improvements: EPMis built for seamless integration with point-of-care or centralized PCR tests world-wide; EPMwill achieve FDA approval as the first integrated stabilization and extraction preservation media for SARS-CoV-2; and EPM will be clinically validated with leading research centers for expanded community surveillance testing of SARS-CoV-2. Our proprietary buffer protects free nucleic acids by multiple mechanisms, destroys virus to protect testing personnel, and facilitates simple, high-throughput extraction of entire samples. In vitro testing has demonstrated the capabilities of this platform to significantly improve testing performance in the most challenging low viral load samples.",2020,2022,Convergent Genomics Inc,999975,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2016 +C07140,3R01AG064802-02S2,Pilot study of RTB101 as COVID-19 prophylaxis in older adults with amended research plan and budget,"Abstract Given the elevated mortality of COVID-19 infections in older adults (Wu et al 2020), there is anurgent need to evaluate medicines that may prevent severe disease in these vulnerable patients. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral respiratory tract infection (RTI) (York AG et al. 2015). Importantly, RTB101 was also observed to upregulate interferon-stimulated pan-antiviral gene expression, decrease the levels of inflammatory cytokines in serum, and decrease the incidence and severity of viral respirator ytract infections including coronavirus infections when given as prophylaxis during winter coldand flu season to older adults (Mannick et al. 2018, Mannick et al., 2019). Therefore we hypothesize that RTB101 will decrease the incidence and severity of COVID-19 when given as prophylaxis to older adults. Before undertaking a large well-powered trial for this indication, we propose to undertake a pilot study to determine the feasibility of recruiting, consenting, screening and randomizing quarantined outpatient populations of older adults who are predicted to be at increased risk of developing COVID-19 (Specific Aim 1), assess whether COVID-19symptoms can be tracked using an eDiary in older adults (Specific Aim 2), and obtain preliminary data on the incidence and severity of COVID-19 in subjects treated with RTB101 as compared to placebo (Specific Aim 3). The data generated in the trial will be used to help optimize the study design of a larger adequately powered study to determine if RTB101 is effective as COVID-19 prophylaxis in the older adults.",2020,2024,Restorbio Inc,51250,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase) | Prophylactic use of treatments,2019 +C07141,1U54CA260582-01,Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID),"Overall Project Summary Stemming the spread of COVID-19 will require research that cross-cuts basic, translational, and applied sciences. The Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID) is proposed as a transdisciplinary entity to understand the interface between exposure risk, transmission, immune responses, disease severity, protection, and barriers to testing/vaccination, with the goal of improving population health and clinical outcomes. The Center will utilize state-of-the-art serological and molecular tests,developed at OSU, in a longitudinal study of first responders, a group at continual high risk of SARS-CoV-2 exposure, as well as their household contacts. Through the proposed work, STOP-COVID investigators will understand critical aspects of: (i) transmission in both asymptomatic and symptomatic individuals, (ii) immune,host, and viral determinants of disease outcome, and (iii) factors associated with immune protection. Center investigators will also identify best practices for communication of test results and information about COVID-19 to improve understanding of risk, transmission, and protection, while reducing access barriers to testing. The Center to STOP-COVID will: Aim 1 Develop Institute Infrastructure through three shared resource cores: 1. An Administrative Core that provides overall direction and leadership, coordinating all Center activitiesas well as Project-Core-SeroNet interactions; 2. A Testing and Biorepository Core, whose role is to perform first-tier serologic and viral testing during our longitudinal study using high throughput ELISA and neutralization assays developed at OSU, and cost-shared by OSU; and 3. A Data Management and Analysis Core that will provide project investigators with a centralized resource for biostatistics, bioinformatics, epidemiology, and psychometrics expertise. Aim 2: Conduct three innovative research projects to address: Project 1: Parallel serological and viral testing to determine COVID-19 prevalence, transmission, and protection in extended first responder cohorts. This project will also generate serology data for vaccines or mAbs, once available to this presumably high-priority group; Project 2: Serologic and molecular determinants of COVID-19 severity and immune protection. This project will evaluate COVID-19 serological responses in the context of SARS-CoV-2and common cold CoV (CCCoV) antibodies, using novel assays specific for a panel of antigens. Project 2 also will employ transcriptomics to understand how host genetics, CCCoV, other respiratory viruses, and immune responses contribute to pathogenesis; and Project 3: Responding to changing serological and viral information around COVID-19. This project will incorporate results from Projects 1 & 2 and SeroNet to inform best practices in risk communication, provide behavioral guidance to decrease transmission, and enhance protection from disease. Aim 3: SeroNet Participation and Sharing of Data and Best Practices. We will leverage STOP-COVID infrastructure to share data, results, reagents, and best practices with SeroNet, which will drive new discoveries and their translation into actionable strategies for implementation across all groups affected by COVID-19.",2020,2022,Ohio State University,3952831,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis | Approaches to public health interventions | Communication",2020 +C07142,3U24HG010262-03S2,The AnVIL Data Ecosystem,"PROJECT SUMMARY In response to the COVID-19 pandemic, the Host Genetics Initiative (HGI) has formed to generate, share, andanalyze data to identify the underlying genetic determinants of the SARS-CoV-2 infection and disease, including the severity in symptomatic presentation and associated outcomes, as well as the development of hypotheses for drug repurposing. To achieve the aims of the consortium, the need for a mechanism to ingest data and make it broadly available for researchers arose. With the National Human Genome Research Institute's commitment to the same goals, the AnVIL, which is predicated on providing a cloud environment for the analysis of large genomic and clinical datasets, became the eminent choice to serve as a data repository and analysis platform for the consortium. As the technology has been developed through the parent grant, the aims proposed for this grant allows the AnVIL to provide scalable support for the Host Genetics Initiative in their utilization of the AnVIL. The specific aims include: • Aim 1: Scale the data Ingest processes for genotypic, phenotypic, clinical report data and metadata to support the expected influx of data from the Host Genetics Initiative • Aim 2: Utilize the Data Use Oversight System (DUOS) to facilitate expeditious data governance and access requests • Aim 3: Dissemination of data for researchers via featured workspaces done in partnership with the Host Genetics Initiative • Aim 4: Provide support for new data generator and user communities Through the implementation of these aims over the course of one year, we will enable the data that is generated by the members of the Host Genetics Initiative to be broadly shared and analyzed with researchersinside and outside of the consortium, which will serve to contribute to the global knowledge of the biology of SARS-CoV-2 infection and disease.",2020,2023,Broad Institute Inc,217232,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2018 +C07143,3R01GM123306-01A1S1,Statistical Methods and Algorithms for Population Genomic Inference,"Project Summary/Abstract: The proposed supplement is in response to the ""Notice of Special Interest (NOSI) regarding the Availability of Urgent Competitive Revisions for Research on the 2019 Novel Coronavirus (2019-nCoV)."" In particular, it is in response to the stated NIGMS Interests: ""Incorporation of data related to the 2019-nCoV into ongoing researchefforts to develop predictive models for the spread of coronaviruses and related infectious agents."" The proposed research extends several aims of the existing grant NIH 5 R01 GM123306 to develop predictive models of the spread of Coronavirus and link these models to genomic variation in hCoV19. Specifically, the proposed research extends Aims 1 and 2 of the original proposal to develop new methods to infer admixture events and recombination among lineages of hCoV19. Recombination is an important factor in the evolution of Coronaviruses and is linked to changes of virulence and transmissibility and is therefore an important parameter of predictive models. The proposed research also extends Aim 4 of the current award by: (1) implementing ""tip-dating"" using viral sampling times to calibrate divergence-time estimates under a relaxed-molecular clock model, and; (2) implements realistic epidemiological priors for gene trees. These extensions allow important epidemiological parameters, such as R0, to be inferred from genomic sequence data while allowing for temporal changes in contacts between infected and susceptible individuals and changes in sampling (intensity of genetic testing) over time across geographic areas. Because CoV19 has a relatively low mutation rate and is under strong purifying selection, it is important to develop integrative methods for analyzing the genetic data that incorporate information from other sources (travel histories, testing regimes, social distancing measures, etc) and maximize the utility of the sequence data. Implementing such an integrative approach is straightforward using the Bayesian framework proposed. The new priors we implement will allow allow external sources of information to be incorporated. The parameters estimated in the preceding aims are essential for constructing predictive simulations of hCoV19. The proposed research extends Aim 6 of the original proposal to develop new simulation methods for predicting the progress of the pandemic from a molecular-genetics perspective. We will develop and implement these methods in open-source software for jointly predicting both the spread of the COVID-19 pandemic through time and the changes in the genomic variation of SARS-CoV-2 under different mitigation strategies. These simulations will accommodate the selective constraints on the genome inferred from phylogenetic analyses of related Coronoaviruses. Genetic variation is important both for understanding the potential power of different genetic sampling strategies for analyzing the progress of the pandemic and for predicting the likelihood that adaptive changes may occur in CoV19 that could impact the severity of the illness and other biologically important features among infected individuals. Predictive modeling of genomic variation in hCoV19 will be useful for designing sequencing strategies to track the progress of the pandemic and for evaluating the reliability of estimates of epidemiological parameters obtained using phylodynamic inference methods.",2020,2024,University Of California-Davis,206764,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Impact/ effectiveness of control measures",2020 +C07144,3P30CA013696-45S3,Exploring Coronavirus-specific T Cell Responses for Immunomonitoring and Adoptive Immunotherapy of COVID-19 in Cancer Patients,"The outbreak of novel coronavirus (SARS-CoV2) causing Coronavirus Disease 2019 (COVID19) has disproportionally affected vulnerable populations including elderly and patients with co-morbidities, including history of cancer and hematopoietic stem cell transplant (SCT) and other defects of immunity. Here we will study the ex vivo T cell responses to SARS CoV2 and related hCoVs 229E and OC43 as a measure of immunocompetence (future diagnostics) and as a possible adoptive transfer strategy (prophylaxis) in high risk patients. Long-lived coronavirus-specific T (CoVST) cell memory responses exist in survivors of SARS and MERS infections and recently described in COVID19 survivors and some unexposed individuals, likely because of the previous exposures to common human CoVs (hCoVs, i.e. 229E and OC43). Based on our preliminary data we hypothesize that cross-reactivity between SARS-CoV2 antigens and their counterparts from common hCoVs exists, potentially contributing to broader anti-CoV protection in some individuals. Responses in cancer patients and SCT recipients (exposed and unexposed to SARS-CoV2) will be characterized in comparison to healthy controls (exposed and unexposed) as a basis for the development of the future research/diagnostic tool evaluating T cell immunity against SARS-CoV2 in correlation with serological testing. Ex vivo generated virus specific T (VST) cells have emerged as a powerful, safe, and cost-effective strategy allowing for rapid induction or restoration of anti-viral immunity. We hypothesize that it is feasible to efficiently induce and expand T cells concurrently recognizing immunodominant antigens of SARSCoV2 and common hCoVs using our standard clinically compatible methodology as a strategy for developing cell-based immunoprophylaxis. Ultimately, we will scale up the manufacturing process of potent cross-reactive allogeneic or autologous CoVSTs and rapidly obtain IND approval providing the basis for the future Phase I safety and feasibility study of adoptive transfer immune prophylaxis for SCT recipients and other vulnerable subjects with cancer as the rapidly accessible ex vivo alternative to vaccination.",2020,2025,Columbia University Health Sciences,162000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,1997 +C07145,3P30CA046934-32S7,Boosting T-cell immunity against COVID19 after CAR T-cell therapy by vaccination,"Summary COVID19 is spreading rapidly across the globe and has caused more than 400,000 deaths, most of which occurred in people with underlying comorbidities. Most patients presented for chimeric antigen receptor (CAR)T-cell therapy against B-cell malignancy have poor immune function. Their immune function is further suppressed by lymphodepleting regimens administered before CAR T-cell infusion and B-cell aplasia and hypogammaglobulinemia caused by CAR T cells. Thus, patients treated with CAR T-cell therapy are at a higher risk of COVID19-related morbidity and mortality. However, whether COVID19 vaccines induce immuneprotection in patients treated with CAR T-cell therapy remains unknown. Studies have suggested that T-cell immunity is critical to the control of infection by human coronaviruses. In addition, SARS-CoV-specific memoryT cells but not memory B cells persist in patients long after recovery from infection. Thus, given the importanceof antiviral T-cell immunity and depletion of B cells in patients treated with CAR T-cell therapy, it is critical to understand how B-cell malignancy and CAR T-cell therapy affect long-term T-cell immunity induced by COVID19 vaccines. In the last twelve years, we have identified multiple signaling pathways essential for antiviral T-cellimmunity and gene signatures associated with effective long-term immune protection by antiviral T cells. In particular, we have recently characterized a stem-like CD8 T cell population that resists T-cell exhaustion andexhibits superior immunity against viruses and tumors. These stem-like CD8 T cells can be induced by vaccination and persist decades in human after vaccination. Thus, stem-like CD8 T cells might endure the immunosuppression caused by malignancy and cancer treatment and mediate potent immunity against SARS-CoV-2. Here, we hypothesize that stem-like CD8 T cells induced by a COVID19 subunit vaccine mediate long-term antiviral immunity after CAR T-cell therapy. Most current experimental models of CAR T-cell therapy rely on severely immunocompromised mice lacking T and B cells and are not suitable for studying the immune response induced by COVID19 vaccines. To evaluate the vaccine-induced T-cell immunity against SARS-CoV-2 in CAR T-cell treated mice, we will employ a novel mouse model of anti-CD19 CAR T-cell therapy against B-cell ALL using wildtype C57BL6 mice with intact immune system. Our study will shed light on the development of vaccination strategy to generate effective immune protection against COVID19 for patients treated with CART-cell therapy.",2020,2021,University Of Colorado Denver,155500,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,1997 +C07146,3UM1CA121947-14S1,AIDS Malignancy Consortium (AMC),"The parent grant of this supplement is the ANal Cancer/HSIL Outcomes Research (ANCHOR) Study, a large multi-site randomized clinical trial and protocol of the AIDS Malignancy Consortium (AMC), UM1CA121947. It is designed to determine if identification and treatment of anal high-grade squamous intraepithelial lesions (HSIL), the anal cancer precursor, is effective in reducing the incidence of anal cancer, similar to the approach currently in place to prevent cervical cancer. Anal cancer has increasing in the general population in both men and women since the 1970s. It is particularly common among people living with HIV (PLWH) and especially men who have sex with men living with HIV (MSMLWH), among whom current incidence exceed 100/100,000 per year (1). PLWH are at high risk of developing anal cancer because of a high prevalence, incidence and rate of persistence of anal HSIL and the causative agent, anal human papillomavirus (HPV) infection (2). The SARS-CoV-2 pandemic has had a dramatic effect impact on the conduct of the study, prompting all ANCHOR study sites round the country to cease screening, enrollment and follow-up of randomized participants in March, 2020. Expectations are that these activities will resume at some sites in May, 2020 with more and more sites resuming normal activity over time. However, apart from affecting normal study activities, SARS-CoV-2 may have additional relevance by impacting on the natural history of anal HPV infection, development and persistence of anal HSIL, and progression from HSIL to anal cancer. This is because of the growing body of evidence that SARS-CoV-2 is shed in stool and may infect the gastrointestinal tract. Nothing is known at present as to whether SARSCoV-2 can infect the anal epithelium specifically, whether it affects the biology of anal HPV infection, how it affects the local immune response, and whether it affects the natural history of anal HSIL. Furthermore, nothing is known about anal SARS-CoV-2 infection in the group at highest risk of anal cancer, PLWH. The ANCHOR study offers an ideal opportunity to begin to address these issues particularly since a high proportion of participants in the ANCHOR Study are from medically underserved minority populations who are also at very high risk of SARS-CoV-2 infection. The focus of this supplement is to describe detection of SARS-CoV-2 in anal swab samples from PLWH being screened for the ANCHOR study; examine its relationship to prevalent anal HPV infection and HSIL in the screening population; and determine its effect on the natural history of anal HPV infection and HSIL by examining its relationship to regression of HSIL and clearance of HPV infection in the subset of enrolled participants randomized to the active monitoring arm.",2020,2025,"Montefiore Medical Center (Bronx, Ny)",149833,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2006 +C07147,3U54MD007598-12S6,Accelerating Excellence in Translational Science (AXIS),"Abstract: This project will use national and local incidence, mortality and testing data, with GIS driven agent-based disease modelling to identify the ""neighborhood effects"" that drive the uneven patterns of transmission and serious outcomes from COVID-19. Neighborhood environments have been associated with chronic disease mortality, disability, cumulative stress, cognitive decline, loss of physical functioning. These same neighborhood effects are implicit in exacerbating disparities in the spread and health outcomes of COVID-19, however the exact mechanisms and the magnitude of the impact of entrenched social disparities specifically onCOVID-19 outcomes are not yet known. The key hypothesis is that agent based disease spread modeling of the existing retrospective COVID-19 data sources at the national and local levels with geospatial data input and spatial-temporal analysis will provide powerful knowledge on the structural factors that influenced the pandemic's spread in local areas and will facilitate the development of valuable recommendations on how to mitigate current and future disparities in impacts of COVID-19 and other future infectious epidemics and pandemics. We will test our key hypothesis and accomplish our objectives via the following Specific Aims.Determine what Counties factors related to the social determinants of health have influenced the spread of coronavirus in the United States. 1) Determine, within the identified Counties, which social determinants have had significant impact on either spread or inhibit spread of CV-19. 2) Determine which populations groups have been impacted more severely in these local contexts and why? 3) Determine what specific recommendations can be made from these findings? The expected outcomes of this research are published manuscripts and scholarly presentations that provide science- based recommendations on the how health authorities and policy makers can proactively address social factors that amplify disease and poor health outcomes in certain communities.",2020,2024,Charles R. Drew University of Medicine and Science,179375,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions,2009 +C07148,3U54MD007598-12S5,Accelerating Excellence in Translational Science (AXIS) - Admin Supplement,"The Disproportionate Impact of COVID-19 Among Racial Ethnic Minority Populations and Other Vulnerable Populations in The United States.Abstract: Charles R. Drew University of Medicine and Science is proposing to coordinate, implement and evaluate a pilot demonstration research project targeting three hundred (300) African American and Latino homeless individuals residing in South Los Angeles who are at high risk for COVID-19 acquisition. The goal of the study is to inform the development of a culturally competent primary healthcare program with a focus on COVID-19 screening, primary prevention education and referral services delivered by trained CDU health professionals. The purpose of the project is to 1. increase knowledge and awareness of the COVID-19 pandemic's impact on African American and Latino homeless populations residing in SPA 6, 2. provide free COVID-19 screening services utilizing the oral swab diagnostic test targeting at risk and vulnerable African American and Latino homeless populations residing in SPA 6, and 3. develop an effective enhanced case management intervention to break the chain of COVID-19 infection among at risk African Americans and Latinos residing in homeless encampments in SPA 6. This is a cross-sectional observational study, whereby the study participants will receive direct primary healthcare services from a newly funded Street Medicine project called the ""MobileHealth Outreach Project"" (MoHOP). MoHOP staff, which will include a physician, FamilyMedicine Residents, Physician Assistants, and graduate students enrolled in the University's Masters in Bio-Medical Sciences and Masters in Public Health programs, will travel with the clinicians to homeless encampments in SPA 6. During this street outreach, we plan to offer free COVID-19 screening services as well as provide COVID-19 primary prevention services in order to mitigate the further spread of COVID-19 among this vulnerable population. Data will be collected from study participants utilizing a baseline pre-test questionnaire to collect thefollowing information: 1. socio-demographic data, 2. data on the study participants' knowledge,attitudes, beliefs and risk reduction behaviors concerning COVID-19, 3. data to assess theparticipants' knowledge of the signs and symptoms of COVID-19 infection, 4. data regarding thestudy participants' knowledge of measures to prevent COVID-19 infection, including effectivemeasures to quarantine and isolate individuals testing positive for COVID-19, 5. data onwhether or not the study participants are knowledgeable about existing resources in the SouthLos Angeles community to obtain COVID-19 screening, and 6. data on how to manage stressand/or depression due to the COVID-19 pandemic. A Core Team, composed of ProfessorCynthia Davis, the PI on the project and Dr. Alexander Rogers, the PI of the CDU MoHOPStreet Medicine Project and Co-investigator on the project, and Co-Investigator and faculty member, Danielle Campbell will lead the project. Mr. Francisco Perez, Executive Director ofGranada on Broadway, a local non-profit agency serving the homeless in South Los Angeles,will assist with the planning, coordination, implementation and evaluation of the proposed study.The Core Team will participate in weekly telephone conference calls in addition tocommunicating daily via email communications. Dr. Rogers will serve as the Preceptor for theCOM Family Medicine Residents, COSH Physician Assistant students and COSH Masters inPublic Health and Masters in Bio-Medical Sciences students who will be completing theircommunity service, Practicum and/or Thesis requirements by volunteering on the MoHOPStreet Medicine Project as part of the CDU Advantage curriculum activities. A Community Advisory Board (CAB) will be established to help guide all phases of the proposed study.",2020,2024,Charles R. Drew University of Medicine and Science,179375,Human Populations,Black | Other | Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified | Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement,2009 +C07149,3R01MH122392-01S1,Reward Re-Training: A new treatment to address reward imbalance during the COVID-19 pandemic,"PROJECT SUMMARYPublic health approaches to reducing the spread of COVID-19 such as social distancing, shelter-in-placeorders, quarantine, telework, and remote learning have produced a sudden and widespread disruption to social networks. The observed disruptions to social networks are leading to increases in social isolation and loneliness and limited opportunities to obtain sufficient reward from day-to-day life activities. Reduced exposure to day-to-day sources of reward can lead to a hypo-reward response to conventionally rewarding stimuli and reduce an individual's motivation to engage in activities that they usually find pleasurable. When insufficient pleasure is experienced from day-to-day life activities, some individuals may be more likely to seek out stimuli that can immediately and powerfully activate neural reward pathways. A hyper-reward response to disorder specific stimuli may develop as individuals seek out larger quantities or more frequent exposure to a limited range ofintensely stimulating sources of reward. Collectively, this may produce a reward imbalance such that individuals achieve very little reward from typically enjoyable day-to-day life activities and instead achieve most of their reward from behaviors or substances that have high potential for adverse consequences. While the reward imbalance is likely a relevant maintenance factor for numerous mental health conditions, there is a strong body of literature suggesting that individuals with an eating disorders (ED) characterized predominately by binge eating experience a reward imbalance. Prior to the COVID-19 pandemic, our team began to develop a novel group-based treatment approach for transdiagnostic binge eating that we call Reward Re-Training (RRT). RRT is designed to indirectly change disordered eating behaviors by directly focusing on building a more rewarding life. RRT hypothesizes that reductions in binge eating will occur as life becomes more rewarding because individuals will no longer need to rely on binge eating as a primary source of momentary reward. RRT notes that in order to live a satisfying life, individuals need to experience an adequate amount of reward in two overlapping yet distinguishable domains:momentary reward (i.e., the active experience of pleasure in the moment) and sustained reward (i.e., a deeper and more long-lasting sense of fulfillment and meaning that arises from building a personally valued life). A keyaspect of RRT is an emphasize on building lasting and meaningful social relationships given the clear evidence that social activities and social connection can enhance both momentary reward and sustained reward. In the current study, we will revise our existing 10-session group RRT treatment manual to specifically address the challenges in enhancing both momentary and sustained reward during the COVID-19 pandemic. We will conduct a small pilot RCT that will randomize individuals to receive either 10-sessions of RRT (n=30) orsupportive therapy (n=30), both delivered as group-treatments via videoconferencing software, to evaluate the feasibility, acceptability, target engagement and preliminary estimates of efficacy for RRT.",2020,2024,Drexel University,232682,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C07150,3R01MH118270-02S1,Efficacy of a Healthy Lifestyle Intervention to Prevent Depression in Older Spousally-bereaved Adults-Supplement,"PROJECT SUMMARY/ABSTRACTOlder spousally-bereaved adults are at very high risk for major depressive disorder (MDD). In the age ofCOVID-19, the inability to engage in rituals that support the grieving process will make it much more difficult tocope with the death of a spouse. This proposed Administrative Supplement leverages our funded R01 ""Efficacyof a Healthy Lifestyle Intervention to Prevent Depression in Older Spousally-bereaved Adults"" (WELL) toincrease the reach, uptake, and sustainability of our existing behavioral-health intervention to accommodateolder spouses bereaved by COVID-19 who are seeking prevention and self-management strategies to managepsychiatric symptoms both during and following the pandemic. We will use digital advertising to optimize reachand access in geographic locations heavily impacted by the COVID-19 pandemic. To promote adherence toand sustained use of WELL, we will use existing data (K01 MH103467) to identify individual and intervention-level characteristics that are associated with discontinuation vs sustained use of digital interventions for mentalhealth support. Additional measurements of death, dying, and bereavement (preparedness for death, lack ofclosure, social isolation, and loss of mourning rituals) will be obtained for the 100 participants recruited over theSupplement's two-year time frame. The data will be used to examine both the impact of COVID-19 death ondepression symptoms (collected through this supplement) and trajectories of depression symptoms over oneyear (collected through this supplement during the WELL follow-up time period). The aims of the proposedresearch will examine in older spousally-bereaved adults at high risk for MDD (due to subthreshold symptomsof depression) (1) whether depression symptom burden is higher in older spouses bereaved by COVID-19 thanthose bereaved by other causes of death; and (2) whether COVID-19 bereavement is associated with otherpsychopathological conditions including anxiety, post-traumatic stress, suicidal ideation, and prolonged griefdisorder(s). In sum, WELL provides a unique opportunity to examine the relationship between COVID-19 deathand surviving spouses' psychiatric symptoms in a large longitudinal study of community-dwelling older spousesparticularly vulnerable to MDD due to spousal bereavement.",2020,2022,University Of Pittsburgh At Pittsburgh,180020,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C07151,3UH3TR002097-04S1,Drug development for tuberous sclerosis complex and other pediatric epileptogenic diseases using neurovascular and cardiac microphysiological models,"Although COVID-19 is recognized primarily as a respiratory infection and the majority of deaths from thedisease are attributed to pulmonary failure, it has become increasingly apparent that the SARS-CoV-2 virus,either directly or indirectly, affects all major organ systems with a confounding degree of variability thatcomplicates the identification of effective therapeutics. In particular, the central nervous system (CNS) andvasculature both seem to play a significant role in disease progression, and CNS symptoms have correlatedwith poorer outcomes in COVID-19 patients. It is hypothesized that the CNS and vasculature each influencepathological dysregulation of immune response, but very little is known about how they respond and possiblycontribute to disease progression. No single therapeutic agent has emerged that broadly neutralizes COVID-19disease progression, which strongly suggests that any effective treatment strategies will need to address notonly effects of SARS-CoV-2 infection in the lungs, but also inflammation in many organ systems, which in turnwould require therapeutic access to the CNS. Thus, understanding the interactions between the lungs and theCNS is critical to identifying treatments capable of improving the prognoses of COVID-19 patients and reducinghospitalization rates and mortality. This project will evaluate how SARS-CoV-2 infection in the lungscontributes to both the organ dysfunction in COVID-19 and potential CNS infection, and how well thecombination of anti-viral and anti-inflammatory drugs addresses CNS involvement in COVID-19. These goalsdemand a physiologically relevant in vitro platform that fully recapitulates the systemic immune and cytokinestorm responses following infection of airway epithelium associated with the most severe cases of COVID-19and that can be readily used in the Biosafety Level-3 (BSL-3) facilities required for studies of this highlyinfectious respiratory disease. This project will implement a two-organ microphysiological system (MPS) modelthat uses an existing NeuroVascular Unit (NVU)/blood-brain barrier tissue chip for the CNS component,repurposes the NVU as an Airway Chip for the lung component, and converts both chips to gravity perfusionfor ease of use in BSL-3 facilities. The aims are to 1) model COVID-19 infection and innate pulmonaryresponse in the Airway Chip, 2) couple the NVU and Airway Chip to evaluate how the response of the AirwayChip to COVID-19 infection affects the function of the NVU, as required to establish therapeutic benchmarksfor drug testing, and 3) screen FDA-approved drugs for efficacy in treating negative symptoms in theNVU/Airway Chip model. A comparison of infection of the separate NVU/CNS and Airway tissue chips withinfection of the coupled-chip system will help determine the infectability of each MPS model and the viralcapacity to cross the blood-brain barrier into the CNS. Candidate FDA-approved drugs will be tested for theirability to affect viral infection, replication, and cytokine production in both microphysiological systems.",2020,2022,Vanderbilt University,1142940,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Prophylactic use of treatments",2020 +C07152,3K01HD087479-04S1,Biopsychosocial Pathways Linking Discrimination and Adolescent Health,"Project Summary: Incidents of discrimination are part of the everyday life experiences of adolescents ofcolor, yet we know almost nothing about how discrimination gets under the skin to influence adolescent health.Although discrimination (the focus of the original K01) is a clear stressor in the lives of youth, with the COVID-19 pandemic, an unexpected and potent new stressor has been introduced to adolescents' daily lives.Moreover, the stark inequities in health and disease burden borne by the poor and racial/ethnic minorities inthe U.S. have been laid bare by the COVID-19 pandemic, and certain groups are encountering discriminatorytreatment tied directly to the pandemic. As such, the COVID-19 pandemic, along with the discriminationexperienced by adolescents both within and outside the context of COVID-19, could initiate or furthercontribute to health disparities tied to race/ethnicity and social class observed in adult populations.Adolescence is a key time to study these stress processes since the social-cognitive ability to recognizediscriminatory treatment emerges in the second decade of life, as do effective coping mechanisms for dealingwith major life stressors, such as those tied to the current pandemic. My proposed competitive revision targetsbiodemography and the pathways by which COVID-19 stress/stressors influence developmental trajectories ofadolescent health and well-being. In addition to integrating COVID-19 stressors into the biopsychosocial modeltested in my original K01 (Aim 1), I introduce two new primary aims for my research project as part of the K01competitive revision: (1) Document the extent to which COVID-19 is influencing all aspects of the daily lives ofadolescents and (2) Examine the extent to which COVID-19 is disrupting trajectories of well-being. To addressthese new research aims, I will leverage three waves of rich longitudinal data from a racially/ethnically andsocioeconomically diverse sample collected pre-pandemic (annually from 8th to 10th grades) with three newdata collection waves collected during the pandemic (11th and 12th grade). These data will allow me todocument how COVID-19 may be disrupting trajectories and psychological well-being, physical health, andacademics, the extent to which these disruptions are temporary (denoting recovery) versus long-lasting, who ismore likely to recover, and how relationships with important others (families, teachers/schools, friends) mightmitigate disruptions. Along with these survey data, I will integrate interviews to delve deeply into COVID-19 andthe lived experiences of adolescents during the pandemic as well as daily diaries to capture how dailyprocesses, social interactions, and well-being are influenced by COVID-19 stressors. Texas relaxed socialdistancing requirements May 1, 2020 without reaching goals for adequate COVID-19 testing, and it thusprovides an important backdrop for understanding how this global pandemic is compromising adolescents'trajectories in real-time. This will provide invaluable information for those designing and implementinginterventions for adolescents as they weather major life stressors and larger sociohistorical events.",2020,2022,"University Of Texas, Austin",71337,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2017 +C07153,3U54CA143924-12S2,2/2 Partnership for Native American Cancer Prevention,"The Navajo Nation is reporting the highest per-capita coronavirus infection rate in the United States (US) with 3.6% infected and a 4.7% case fatality rate, despite quickly responding to the first cases with prevention messaging and community lock-down measures. Chronic conditions like diabetes and obesity, prevalent on the Navajo Nation, have been associated with severe COVID-19 illness. Although several factors have contributed to the high incidence of infection in this population, cultural and economic factors are playing a major role. These conditions complicate maintaining medical care while engaging with the recommendations to reduce COVID-19 transmission. The impact of COVID-19 for the Navajo Nation can become broader than the immediate morbidity and mortality; cancer prevention and early detection screenings may have been postponed, cancer treatments may have been stopped or delayed. It is unknown how SARS-CoV-2 infection and the measures to prevent infection will impact health care delivery, including cancer screening, detection, and care. To address these disparities and to better respond to the impact of the pandemic within one of the most impoverished regions of the US, we propose to use a multimethod approach to determine the impact of the COVID-19 pandemic from the perspectives both the health care providers and facilities and from the individual patients' perspective on health related care delivery, including cancer prevention, early detection, screening, diagnosis, and treatment planning, and the interaction of chronic diseases with SARS-CoV-2 infection. Specifically, we will 1) investigate provider/health care worker perceptions about COVID-19 impacts using online surveys and semi-structured interviews and 2) investigate changes in patients' and communities' care seeking capacity, using online and telephone surveys and Zoom-based focus groups with members of the community and with cancer patients. Our research team from two universities and Navajo community members is uniquely suited to respond because of our current partnerships with the Navajo Nation and medical facilities. Beyond understanding what factors are contributing to the high transmission on the Navajo Nation, the data collected for this project may allow for future assessment of the impact of delay in cancer treatment or detection for patients. Through surveys, semi-structured interviews, and focus groups, we will provide a broad assessment of the experiences of Navajo households and Navajo cancer patients throughout the pandemic and how this widespread community transmission and infection has influenced access, utilization, and quality of health care.",2020,2024,University Of Arizona,166201,Human Populations,Other,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2009 +C07154,1U54CA260591-01,Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2,"ASBTRACT OverviewEvery day, Californians continue to experience high levels of exposure to the novel severe acute respiratorycoronavirus 2 (SARS-CoV-2) virus. There is an ever-growing urgent need to better understand the nature ofexposures, course of illness and recovery, and potential for immunity among persons at particularly heightenedrisk for the worst COVID-19 outcomes. As part of a rapid scientific response to the present public health crisis,we convened on March 18, 2020 a collaborative of frontline clinicians and scientists to form the Coronavirus RiskAssociations and Longitudinal Evaluation (CORALE) studies (corale-study.org). We established two base studycohorts with enrollment centered on (i) patients with suspected or confirmed COVID-19 treated in our healthsystem (currently N>8,300) and on (ii) healthcare workers directly or indirectly involved in delivering their care(currently N=6,679). In response to NIH RFA-CA-20-038, we are now highly motivated and prepared to leverageour existing infrastructure to directly address the critical need for comprehensive longitudinal data collection andanalyses to advanced our understanding of SARS-CoV-2 risks, the course of disease, the nature of recovery,and the potential for immunity across populations at risk. By establishing the CORALE-SeroNet U54 program,our goal will be to form a robust and sustainable structure of academic activities centered on investigating theresponses elicited by SARS-CoV-2 exposure and the extent to which carefully phenotyped clinical and molecularprofiles can signal robust immune reconstitution and complete functional recovery. Our study will be centeredon the ethnically/racially diverse population served by our health system in Los Angeles, given then critical needfor more knowledge regarding the determinants of COVID-19 related risks in these minority subgroups. Ourscientific objectives will be achieved by an outstanding collaborative team of clinician-scientists, epidemiologists,immunologists, basic and translational scientists, analytical chemists, and biostatisticians. Leveraging ourcollective experience, resources, and infrastructure at major academic institutions from across SouthernCalifornia (Cedars Sinai, UCSD, UCLA, and USC), we will advance the scientific enterprise through the threedistinct yet closely integrated research Projects: Project 1 will elucidate the natural history and longitudinaltrajectories that represent the diversity of SARS-CoV-2 exposure, infection, recovery, and clinical immunitypatterns across the spectrum of persons at risk. Project 2 will investigate the determinants of SARS-CoV-2response in persons with altered innate immune function, with a focus on individuals with pre-infectionsusceptibility traits (e.g. metabolic disease states); and, Project 3 will investigate the determinants of SARS-CoV-2 response in persons with altered adaptive immune function, with a focus on individuals with immune-altered status arising from select malignancies, autoimmune disease, and/or their directed therapies. As a wholethis research program will integrate population, clinical, translational, and basic science resources with a world-class investigator team to meet the urgent need for new mechanistic insights and therapeutic approaches toaddress key knowledge gaps regarding SARS-CoV-2 susceptibility and potential for immunity.",2020,2022,Cedars-Sinai Medical Center,3386294,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Disease susceptibility",2020 +C07155,3P50HD103525-01S1,WUIDDRC Supplement-Supporting the health and well-being of children with intellectual and developmental disability during COVID-19 pandemic,"PROJECT SUMMARY/Abstract: Children with intellectual and developmental disabilities (IDD) are at major risk of irreversible harm from theCoronavirus Infectious Diseases 2019 (COVID-19) pandemic, particularly those from underserved populations.Not only are they at dramatically higher risk of becoming infected with Severe Acute Respiratory SyndromeCoronavirus-2 (SARS-CoV-2) and death from COVID-19, but children with IDD are vulnerable to the negativeimpact of school closure. School districts provide critical services beyond the education, including nutritional,social, therapy (physical, occupational, and speech-language) and healthcare services. Risks are heightened forchildren with IDD, as they are often unable to wear masks, practice social distancing and/or implement effectivehand hygiene. Access to rapid and reliable SARS-CoV-2 testing is essential for children with IDD and schoolstaff in order to safely return to school. Members of our research team have developed an innovative, scalable,low-cost method for SARS-CoV-2 testing using saliva samples. Investigators at the Washington UniversityIntellectual and Developmental Disabilities Research Center (IDDRC@WUSTL), in collaboration with theUniversity of Missouri-Kansas City Institute of Human Development and the Kennedy Krieger Institute inMaryland (which includes an IDDRC, the Maryland Center for Developmental Disabilities, and the KennedyKrieger School Programs), are ideally positioned to determine the best implementation strategies to maximizeuse of a saliva-based SARS-CoV-2 diagnostic test for vulnerable children and school staff in a school setting.The IDDRC@WUSTL has a long-standing relationship with the Special School District (SSD) of St. Louis County,whose mission is to serve children with IDD, and the national network of the Association of University Centerson Disabilities (AUCD). First, we will determine the most effective messaging and implementation strategies tomaximize weekly SARS-CoV-2 testing in a school setting. In this adaptive clinical trial, we will administer 52,000diagnostic tests to students and school staff at SSD, whose student population is 48% Black. Second, we willmeasure national attitudes among parents/guardians of children with IDD and school staff regarding the impactof COVID-19 and the importance of SARS-CoV-2 testing. At the successful completion of this project, we willhave improved the acceptance, adoption, and process for SARS-CoV-2 diagnostic testing in a school-basedsetting to enable delivery of critical educational activities for children with IDD in an underserved community. Byidentifying the most effective methods for SARS-CoV-2 testing in a vulnerable population of children with IDD,we will establish a blueprint for wider adoption of COVID-19 mitigation efforts, such as vaccination.",2020,2025,Washington University,3734054,Human Populations,Black,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other | Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Policies for public health, disease control & community resilience",Diagnostics | Disease pathogenesis | Approaches to public health interventions,2020 +C07156,3U19MH113136-04S2,Protecting Native Families from COVID-19: Radx Initiative,"PROJECT Summary: White Mountain Apache-Navajo-JHU research partners are uniquely positioned and prepared to advance COVID-19prevention science through the Emergency Competitive Revisions for Community-Engaged Research on COVID-19Testing among Underserved and/or Vulnerable Populations (NOT-OD-20-121). Since April 2020, we have implementedcomprehensive COVID-19 mitigation activities with Navajo and White Mountain Apache nations, who have had thehighest rates in the US, and honed capacity for home-testing and obtaining rapid results. Our experience and datareview with tribal divisions of health and the Indian Health Service has uncovered barriers to testing, protectivebehaviors, isolation and care-seeking among two high risk sub-groups that must be addressed for successfulmitigation. The first group are elders, ages >65, who have the highest case fatality rate in both communities and aredeeply revered as teachers of cultural practices and languages. A significant portion of elders are currently resistant totesting due to cultural beliefs and fear, and slow to seek care when symptoms worsen. The second group are youngadults, ages 18-34, using substances, who have the highest proportion of cases per capita, are less likely to social-distance or isolate, and are more transient, moving among multi-generational households. This project will apply a 2x2factorial design to evaluate two interventions for these high-risk groups: 1) a culturally tailored, age-specificMotivational Interviewing (MI) intervention to promote testing, protective behaviors and appropriate isolation andcare-seeking, and 2) a COVID-19 symptom (CS) text-based monitoring system designed to shorten time betweensymptom onset and testing, while incorporating GIS to assist with route-mapping for home-based follow-up. MI hasstrong evidence in American Indian communities, including our team's proven MI intervention for improved STI/HIVtesting. The CS System builds on our experience with mobile health surveillance and embedded GIS/GPS tracking. Ourthree primary aims are: 1: Use Community Based Participatory Research to apply knowledge of relevant facilitators andbarriers to create, pilot, implement, and evaluate through an RCT a culturally tailored brief MI intervention to promoteCOVID-19 testing when experiencing symptoms, appropriate preventive behaviors, and isolation and care-seeking whenpositive among elders (ages >65 years) and young adults with a recent history of substance misuse; 2: Implement andevaluate through a RCT a daily CS monitoring system with alerts, mechanisms for participants to request home-testingwhen experiencing first symptoms, and GIS routing for those responding to text-based alerts; and 3: Evaluate therelative merits of MI or CS alone or combined on testing and time to testing when experiencing symptoms, andadherence to isolation and care-seeking recommendations when positive using a 2x2 factorial design. Our secondaryaims will explore if a) cultural identity and connectedness; b) substance use or mental health factors (depression,anxiety, suicidality); and c) age and sex moderate intervention response. If aims are achieved, we will make rapidadvances in diagnostic testing strategies for the most underserved and high-risk populations in the US.",2020,2022,Johns Hopkins University,3517791,Human Populations,Other,Adults (18 and older) | Older adults (65 and older),Rural Population/Setting,Drug users | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2017 +C07157,3P50CA244289-02S1,Building Research in Implementation and Dissemination to close Gaps and achieve Equity in Cancer Control (BRIDGE-C2) Administrative Supplement,"This supplement will explore how the COVID-19 pandemic is impacting cancer screening and prevention (i.e., cancer preventive care) among patients receiving care in community health centers (CHCs) by leveraging the The Building Research in Implementation and Dissemination to close Gaps and achieve Equity in Cancer Control (BRIDGE-C2 ) Center Implementation Laboratory infrastructure. CHCs adapted and changed the way they deliver care during the current pandemic. For example, our Laboratory CHCs showed an 80% decline of in-person office visits, March to April 2020, in which cancer preventive care is typically delivered. This supplement will allow our team to collect the data needed to inform and align the research of our BRIDGE-C2 Center Parent Grant with the new realities of providing healthcare during the COVID-19 pandemic. We will track and understand the implementation strategies made by CHCs to change healthcare delivery processes and priorities, especially cancer preventive care, and share these critical lessons with a variety of stakeholders including the Implementation Science Centers in Cancer Control Program (ISC3 ) and CHCs across the US. With this supplement we will extend the work of our Parent Grant to answer the following questions: (1) What impact has COVID-19 had on the delivery of cancer preventive care; (2) What are the within and across state variations in CHC response to local levels of the COVID-19 outbreak and state / county actions; (3) What processes did CHCs use to adapt existing or adopt new strategies and implement operational changes to realign care with cancer preventive care guidelines in the COVID-19 context; and, (4) How do these findings inform BRIDGE-C2 Center's future work? Once answered, more questions will become apparent leading to larger scale investigations and additional requests for grant funding. The BRIDGE-C2 Center with its national Implementation Laboratory of geographically diverse CHCs caring for over 1.9 million patients impacted by health disparities is uniquely positioned to extend its Parent Grant to quickly answer these important questions. The Aims of this supplement are: Aim 1: Identify and monitor the impact of the COVID-19 pandemic on delivery and receipt of cancer preventive care over a 12-month period; Aim 2: Identify the processes CHCs used, the external support and assistance they received to implement and adapt cancer preventive care to the COVID19 pandemic context, and operational changes employed to realign care with cancer prevention guidelines; and, Aim 3: Rapidly disseminate findings to a variety of relevant stakeholders. This supplemental work will: (1) advance implementation science by understanding how local adaptations were rapidly implemented or deimplemented in a crisis; (2) guide cancer prevention recommendations on identifying new or adapted ways to deliver cancer preventive care; and (3) rapidly distill and widely disseminate critical implementation findings to NCI laboratories and centers, CHCs and other primary care settings.",2020,2024,Oregon Health & Science University,164196,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Health service delivery | Health leadership and governance,2019 +C07158,3U54MD007600-34S2,Center for Collaborative Research in Minority Health and Health Disparities (2),"Project Summary/Abstract:Among patients with COVID19, there is a high prevalence of cardiovascular disease, and >7% of patientsexperience myocardial injury as a result of the infection (22% of critically ill patients). COVID19 maydisproportionately affect people with cardiovascular disease. Previous observations suggest that underlyingcardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized withCOVID19. Furthermore, coagulopathy and vascular endothelial dysfunction have also been proposed ascomplications of COVID19. We propose a supplement to ""Adopting a Precision Medicine Paradigm in PuertoRico: leveraging ancestral diversity to identify predictors of clopidogrel response in Caribbean Hispanics"" todescribe and better understand how the COVID19 pandemic is affecting our established cohort of CaribbeanHispanics with cardiovascular disease. Our cohort is currently made up of 549 patients with coronary arterydisease (CAD), peripheral artery disease (PAD), and/or a history of stroke (CVA) who are currently receivingtreatment with the antithrombotic medication clopidogrel (with or without aspirin). Building on the personalizedmedicine approach we are already developing for this population, we will combine serologic testing to measureindividual exposure to the SARS-CoV-2 virus with their health (symptoms, clinical outcomes, medicalcomorbidities), access to care (including SARS-CoV-2 testing), and household status during the COVID19pandemic. This will allow us to evaluate the true prevalence of SARS-CoV-2 exposure in our cohort, as well asunderstand the phenotypic effects of the virus in our population. These data will shed light on the underlyingbiological pathways involved in COVID-19 pathogenesis. We will then combine data from our cohort with patientshospitalized for acute COVID19 to perform a targeted and untargeted exploratory genome-wide associationstudy of poor clinical outcomes (e.g., hospitalizations, ICU admission, need of mechanical ventilators) in orderto identify potential risk markers or protective genes among Caribbean Hispanics suffering from the disease.",2020,2022,University of Puerto Rico Medical Sciences Campus,187497,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,1997 +C07159,3P30CA047904-32S5,Cancer Center Support Grant Supplement: Clinical Evaluation of a Q GRFT Nasal Spray for Prevention of SARS-CoV-2,"The current approaches of using protective barriers, social distancing and increased hand hygiene to prevent SARS-CoV-2 transmission have economic consequences and variable efficacy at reducing the spread of SARS-CoV-2. Therefore, curtailing the acquisition of SARS-CoV-2 infection via chemoprophylactic strategies is a high priority. SARS-CoV-2 transmission occurs predominantly through oral and nasal routes leading to high viral replication in the oropharynx and nasopharynx. We hypothesize that prophylactic use of antivirals against SARS-CoV-2 via a nasal spray can lead to virus inactivation at the sites of viral entry and replication. Our network of collaborators has shown that the broad spectrum oligomannose-binding lectins, Griffithsin (GRFT) and Q-GRFT, inhibit viral entry of all coronaviruses tested, including SARS-CoV, MERS-CoV and SARS-CoV2. Moreover, delivery of these antiviral lectins to the upper respiratory tract provides significant protection from SARS-CoV, MERS-CoV and paramyxovirus Nipah virus in animal models. Therefore, the PREVENT COVID clinical program is designed to establish the feasibility of this approach by demonstrating that nasal administration of Q-GRFT is safe and acceptable and also ascertain whether levels of Q-GRFT in upper respiratory tract samples are adequate to provide protection from SARS-CoV-2 based on pharmacodynamic assessments of the respiratory tract fluids. Three specific aims are proposed to advance the Q-GRFT nasal spray from bench to the clinic. Aim 1 will collate the results of preclinical studies of Q-GRFT along with chemical composition and manufacturing information related to the Q-GRFT nasal formulation to support the development of the Investigator's Brochure, which will support the filing of an investigator-initiated Investigational New Drug (IND) Application to the US Food and Drug Administration. In Aim 2, pilot studies will be conducted to collect matrices from human volunteers (nasal swabs, nasal washes, saliva samples, pharyngeal swabs and gargle solutions) for development of analytical and biological methods to guide the development of validated assays for the quantification of Q-GRFT in the upper respiratory tract samples obtained from participants in the phase 1 study. In Aim 3, a Phase 1 randomized, placebo-controlled study (PREVENT COVID-101) of the Q-GRFT nasal spray in 45 healthy volunteers will be conducted. Healthy adults ages 18-45 will be randomized 2:1 to receive the Q-GRFT vs identical placebo. Participants will use the spray once, followed by a safety assessment 24 hours later. If safe and acceptable, a second period of daily administration for 14 days will commence. Follow up safety assessments will be conducted after 14 daily applications and the final safety assessment will occur 28 days after initiation of the daily use dosing period. The primary study objective will be to evaluate safety. Secondary objectives include user perceptions and acceptability, assessment of the level of Q-GRFT in respiratory tract samples and the impact of product use on taste and smell. Ultimately, the success of PREVENT COVID program will lead to a safe nasal spray, which can be further evaluated in an efficacy trial to study prevention of coronavirus infection.",2020,2025,University Of Pittsburgh At Pittsburgh,1197257,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,1997 +C07160,1U54CA260492-01,Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2 (JH-EPICS),"Johns Hopkins has broad expertise in the science of human health, with viral immunity, pathogenesis,epidemiology, biostatistics, and surveillance emerging as integral components of the multidisciplinary researchmounted at Johns Hopkins during the current pandemic. We propose development of a Serological SciencesCenter of Excellence: the Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2(JH-EPICS). The overarching goal of JH-EPICS is to distinguish immune responses that protect from thosethat cause pathology during infection. Under the Multiple PI leadership of Drs. Klein and Cox, the JH-EPICSAdministrative Core will ensure resources and samples are available to systematically evaluate innate, T cell,and antibody responses to SARS-CoV-2 in peripheral blood mononuclear cells and serological samples fromCOVID-19 patients sampled longitudinally. JH-EPICS contains three interconnecting Research Projects (RPs).RP1 focuses on innate immune sensing and activation of the human inflammasome by SARS-CoV-2, withevaluation of how anti-SARS-CoV-2 antibodies modulate innate sensing. RP2 uses a novel flow-cytometrybased platform that enables single cell analysis of traditional cell surface markers combined with intracellularstaining for proteins involved in metabolic programming. Using this platform, we have identified distinct myeloidderived suppressor cells (MDSCs) and T cells abundant in COVID-19. RP1 will characterize these MDSCs,while RP2 will explore novel populations of T cells identified in COVID-19 patients. RP2 will also define novelbiomarkers in order to predict severity of disease, track the course of disease, and define novel surrogatemarkers for testing therapeutic regimens. Together, RP1 and RP2 will identify novel therapeutic targets. InRP3, the magnitude, duration, and class switching of SARS-CoV-2-specific antibody isotypes as well as virus-specific neutralizing antibody responses will be analyzed and compared with non-neutralizing antibodyfunctions, e.g., complement fixation and antibody-dependent cellular cytotoxicity, using a novel core set ofserological assays. A centralized Virology Reagent Core will provide antigen for ELISAs, reagents to identifyvirus-specific immune cell populations, inactivated SARS-CoV-2 viruses, methods for quantifying SARS-CoV-2, and access to biosafety level 3 facilities and training needed to perform any experiments involving liveSARS-CoV-2. The Analysis Resource Core will provide statistical modeling and analysis to frame and testhypotheses about the mechanisms mediating the severity of COVID-19 as well as the intersectionality of sex,gender, age, and racial differences in immune mechanisms of COVID-19. In concert with the trans-networkcollaborations, this research will provide significant insights into pathologic immune responses to SARS-CoV-2,identification of novel therapeutic targets, and definition of immunity against SARS-CoV-2 infection. Byuncovering the correlates of protective immunity, JH-EPICS research will further enhance vaccine design andevaluation of vaccine candidates.",2020,2022,Johns Hopkins University,4067207,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies,2020 +C07161,3R00DA041245-05S1,"Stigma, Risk Behaviors and Health Care among HIV-infected Russian People Who Inject Drugs","PROJECT Abstract: The COVID-19 pandemic restrictions to reduce the spread of the SARS-CoV-2 have exacerbated globalinequities. These restrictions may have particularly limited engagement in care of HIV-positive people whoinject drugs (PWID). This longitudinal project aims to qualitatively assess evolving consequences of theCOVID-19 pandemic on health risks and risk behaviors of HIV-positive PWID; and described the impact ofstigma on HIV-positive PWID during the COVID-19 pandemic. We will leverage access to the SCRIPT(R00DA041245) study population (n=108); SCRIPT is a community-based RCT testing the feasibility ofAcceptance and Commitment Therapy as a stigma intervention among PWID with HIV who are not connectedto addiction or HIV care in St. Petersburg, Russia. The SCRIPT study population provides a unique opportunityto understand pandemic impacts on substance use and HIV risk behaviors, as well as health care utilizationamong community-based HIV-positive PWID. This project will inform rights-based, gender-inclusivepreparedness strategies to mitigate adverse pandemic effects and prepare the key population of HIV-positivePWID for future pandemic situations.",2020,2021,Boston Medical Center,160369,Human Populations,Other,Unspecified,Urban Population/Setting,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,Europe,Gender,,,Russia,Russia,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2018 +C07162,3R37CA234239-01A1S1,Lactate as a Driver of Inflammation and Virulence in SARS-Coronavirus Infections,"Aggressive cancer with lung involvement and/or driven by cigarette smoke exposure is a risk factor for death in the context of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) infection. Hence, there is great need to understand factors driving SARS-CoV-2 virulence in the context of aggressive cancer. Patients with SARS-CoV-2 infection are mainly dying from a massive inflammatory response and a severe inflammatory state is also commonly observed with aggressive cancer. Metabolism is the area of biology that studies how cells obtain and utilize energy containing molecules. Lactate is among the most common metabolites in virally infected tissues and cancer. Altered metabolism of inflammatory cells such as macrophages, fibroblasts and T cells is a hallmark of aggressive cancer and may be necessary for the severe inflammatory response to SARSCoV-2 infection. Studies from our group have shown that lactate metabolism drives inflammation in aggressive cancers. Our overall hypothesis is that increased lactate metabolism drives the severe inflammatory state of aggressive cancer, which is increased in the context of SARS-coronavirus infection. Anti-inflammatory drugs in the context of cancer or severe infections have not been effective. The lack of effectiveness might be due to an excessively narrow spectrum (e.g. inhibitors of a particular cytokine) or conversely might be due to toxicity from excessively broad targets (e.g. corticosteroids). However, inhibitors of lactate metabolism may be able to achieve homeostasis with reduced inflammation, thus improving outcomes with SARS-coronavirus infection in the context of aggressive cancer. In Aim 1, we will determine the role of lactate metabolism on SARS-coronavirus virulence in the context of aggressive cancer. In Aim 2 we will determine the role of lactate metabolism in modulating the inflammatory response in SARS-coronavirus infection in the context of aggressive cancer. Understanding the role of lactate metabolism on inflammation and the risk of dying from SARS-coronavirus infections may provide opportunities to develop new treatments for this devastating infection in patients with aggressive cancer.",2020,2024,Thomas Jefferson University,156000,Human Populations,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2019 +C07163,1U01CA260526-01,DISCOVAR:Disparities in Immune Response to SARS-CoV-2 in ARkansas,"PROJECT Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is the causative agent ofcoronavirus disease 2019 (COVID-19) and is responsible for the current pandemic, with 14.4 million totalconfirmed cases of coronavirus disease 2019 (COVID-19) in over 200 countries and territories and more than604,000 deaths as of July 19, 2020. Of these, 3.83 million cases and 143,000 deaths occurred in the UnitedStates (US). Most long-term public health and clinical approaches to pandemic containment are based on thepresumption that infection with SARS-CoV-2 confers immunity against reinfection for at least 1 year. However,understanding of immune responses to SARS-CoV-2 is extremely limited and evidence of conferred immunityagainst reinfection or its duration are lacking. Most concerning is that racial/ethnic minorities bear adisproportionate burden of the incidence, morbidity, and mortality from SARS-CoV-2 infection. To date,explanations for this disparity are postulated as structural racism and discrimination, higher rates of pre-existinghealth conditions, and delayed or limited access to healthcare. However, differences in immune response toSARS-CoV-2 may also play a part in this disparity. Racial/ethnic differences in the immune response are welldocumented for other viral diseases and vaccines, but little is known about immune response to SARS-CoV-2in racial/ethnic minorities. To address this critical gap in knowledge, we will assess and characterize the immuneresponse to SARS-CoV-2 infection in racial/ethnic minorities in Arkansas. To achieve this objective we proposea population-based, observational prospective cohort study comprised of men and women that is a racially,ethnically, and geographically diverse, representative sample of all noninstitutionalized adults residing inArkansas tested by real-time, reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 betweenNovember 2020 and April 2021. The 450-person cohort will be sampled from the statewide COVID-19 testdatabase and followed up to 48 months posttesting. Our first aim is to determine the serological responses toSARS-CoV-2 infection over time by race/ethnicity among RT-PCR confirmed, positive adults in Arkansas. In thisaim we will assess serological response among NH black and Hispanic adults in comparison to NH white adults.Our second aim is to determine the durability of the serological response to SARS-CoV-2 infection over time byrace/ethnicity among RT-PCR confirmed positive adult Arkansans. In Aim 3 we will determine how psychosocialand behavioral factors such as, chronic stress, depression, anxiety, social support, tobacco use, alcohol intake,and sedentary lifestyle, influence the serological response over time to SARS-CoV-2 by race/ethnicity. Weexpect that our results will inform clinical management and prognosis of racial/ethnic minority patients withCOVID-19 and vaccine development. Our findings will also have a significant public health impact for long-termpublic health policies for pandemic containment.q",2020,2022,University of Arkansas for Medical Sciences,1302152,Human Populations,Black | White | Other,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Prognostic factors for disease severity,2020 +C07164,3R01DA047933-02S1,Effectiveness of an Integrated Treatment to Address Smoking Cessation and Anxiety/Depression in People Living with HIV,"Early data indicate that smoking increases the severity of coronavirus disease (COVID-19) symptoms.Individuals living with HIV are more likely to smoke and less likely to quit than those in the general population,placing them at high risk for poor COVID-19 outcomes. Comorbidities associated with HIV, includingcardiovascular disease and chronic lung disease, further heighten risk for a severe course of COVID-19 illness,which has been linked to over 40,000 deaths in the U.S. thus far. To mitigate COVID-19 related healthdisparities and inform intervention strategies, it is crucial to assess the degree to which nicotine dependenceand HIV disease stage affect the onset and progression of COVID-19 in smokers living with HIV. Disruptions to engagement in HIV care and antiretroviral therapy regimens may compromise efforts tomaintain viral suppression and lead to increases in rates of anxiety and depression, both of which are alreadyelevated in individuals living with HIV compared to the general population. Increases in negative affect (anxietyand depression) are established pathways to smoking relapse among smokers living with HIV who may usecigarettes to regulate their negative mood; therefore, increases in anxiety and depression resulting from theCOVID-19 pandemic could impact smoking cessation and relapse. Given the primary outcomes of the parentgrant, we will also examine the ways in which COVID-19 related mental health responses COVID-19influenceuptake of smoking cessation treatments, smoking abstinence, and other relevant smoking outcomes. This proposed Administrative Supplement is responsive to the Notice of Special Interest regarding theAvailability of Administrative Supplements Research on the 2019 Novel Coronavirus (NOSI - NOT-DA-20-047)issued by NIDA and is appropriate to PA-18-591 (Administrative Supplements to Existing NIH Grants).Specifically, our application is responsive to 3 areas of research requested by the NOSI: (1) ""Research todetermine whether substance use (especially smoking tobacco...) is a risk factor for the onset and progressionof COVID-19,"" (2) ""Research on how HIV among persons who use substances may impact the onset andprogression of COVID-19,"" and (3) ""Research using ongoing studies to understand the broad impacts ofCOVID-19 (e.g., anxiety...) on ..., substance use, substance use disorders, and access to addiction treatment."" Through this administrative supplement application we directly address these three areas and propose thefollowing specific aims: (1) to quantify the relationship among baseline nicotine dependence severity, baselineHIV disease stage and their interaction), with COVID-19 outcomes (COVID-19 susceptibility, clinical symptomburden, level of treatment, COVID-19 disease outcome) over up to 2 years of follow up; and (2) quantifymanifestations of negative affect that have emerged in response to the COVID-19 pandemic and the degree towhich these different manifestations impact uptake of smoking cessation treatments over the follow up period.We will achieve these aims by leveraging the of our parent R01 grant.",2020,2023,Massachusetts General Hospital,166958,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2019 +C07165,3UG1CA189854-07S1,Gulf South Minority/Underserved Clinical Trials Network (Gulf South M/U CTN),"Cancer patients overall are at increased risk for developing COVID-19. Both cancer and COVID-19 disproportionately affect minority and underserved populations throughout the country and especially in the Gulf South region of Louisiana and Mississippi. These major health disparities are further magnified in cancer patients living in rural areas and regions of concentrated disadvantage (high poverty). Therefore, there is an urgent need to develop a new Louisiana Cancer-COVID-19 (LA-Cancer-COVID-19 Registry) registry to better understand the impact of the current pandemic on cancer patients in the Gulf South Region. The data obtained will be used to understand how COVID-19 has affected existing cancer health disparities and will prepare us for new national diagnostic and treatment initiatives. The parent grant to this supplement is the Gulf South Minority/Underserved Clinical Trials Network (Gulf South CTN) NCORP. The Gulf South CTN is a partnership between LSU Cancer Center - New Orleans, Ochsner Clinic Foundation, Mary Bird Perkins Cancer Center and LSU- Feist Weiller Cancer Center in Shreveport. Together they oversee a network of 44 clinical sites that have significantly increased enrollments of cancer patients into clinical trials throughout the region. Approximately 50% of patients enrolled are African American. The Louisiana Tumor Registry (LTR), a SEER registry, is also a partner in the Gulf South CTN. The LTR collects all information on cancer patients in the state and has legislative mandate to access all their biological samples and clinical information. For the purpose of this Supplement, the LTR and the Office of Public Health at the Louisiana Department of Health, that oversees the response to COVID-19, have agreed to build this new registry. Therefore the Specific Aims are: 1) Develop the Louisiana Cancer - COVID-19 Registry by linking the LTR cancer registry with the Louisiana Department of Health (LDH) COVID-19 registry. 2) Use the data from the new registry to study the effect of COVID-19 on cancer health disparities in Louisiana, and 3) More effectively participate in national clinical and epidemiological studies through the coordinated data collection efforts of the Louisiana CancerCOVID-19 Registry. The LA-Cancer-COVID-19 Registry will allow us to identify cancer patients who have developed COVID-19 and identify those at high risk for developing the infection and to determine the location of coronavirus ""hot spots"". We will be able to determine how COVID-19 impacts cancer health disparities in different populations and in rural vs urban locations. More importantly the Cancer-COVID19 Registry will better prepare us for a resurgence of COVID-19 or other future pandemics by rapidly deploy being able to deploy diagnostic, treatment or epidemiological trials.",2020,2025,Lsu Health Sciences Center,147000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts | Social impacts,2014 +C07166,3R33AT010125-03S1,Remotely-Delivered Programs Targeting COVID-19 Stress-Related Depression and Substance Use,"Project Summary/Abstract: Remotely Delivered Programs Targeting COVID-19 Stress-Related Depression and Substance Use The COVID-19 pandemic presents an unparalleled level of everyday stress and is likely to increase rates of depression and substance use, potentially overwhelming behavioral health treatment capacity. We have developed a new program (CHA MindWell; CHA-MW) to address the anticipated surge in demand for behavioral health services for our safety-net health system's health system's diverse and socioeconomically disadvantaged population. It has both a screening/monitoring/referral and an early intervention component: First, we implemented remote computerized adaptive testing (CAT-MH®) to stratify patients at risk of stress- related mental illness into 3 tiers: Minimal symptoms or low-risk (Tier 1), mild-to-moderate symptoms or at-risk but not meeting criteria for in-person treatment (Tier 2), and moderate-to-severe symptoms requiring treatment (Tier 3). In standard CHA-MW, CAT-MH is delivered online by email to participants monthly to determine if they are Tier 3 and referral to mental health treatment is needed. Second, Tier 2 patients are referred to a live, online psychoeducational program - Mindfulness-Based Cognitive Therapy for Resilience (MBCT-R), which is an 8-week group adapted from MBCT, which is effective for treatment of stress, anxiety, and depression (known risk factors for substance use), and preventing relapse among patients with recurrent depression. MBCT-R will therefore have impact both during and after COVID-19. When participants enroll in MBCT-R they receive enhanced CHA-MW (i.e., weekly in addition to monthly CAT-MH monitoring), allowing us to closely determine if a higher level of care becomes necessary. We will randomize Tier 2 patients who have mild-to- moderate symptoms of depression (CAT-Depression Inventory 50-75, PHQ-9 equivalency 10-20) in a 3-arm comparative effectiveness RCT to compare MBCT-R + enhanced CHA-MW weekly monitoring to either: a) enhanced CHA-MW weekly monitoring alone (with rapid referral to mental health treatment if needed), or b) an asynchronous internet CBT (iCBT) application + CHA-MW weekly monitoring. We expect MBCT-R to reduce depression symptoms (primary outcome), stress, and indirectly prevent substance use (secondary outcome). For a sub-study within the RCT, we will collect preliminary data using daily diaries to measure stress-related affective reactivity data (upticks in negative affect and/or reductions in positive affect during stress days) and adaptively sample salivary inflammatory cytokines (IL-6, TNF-a, IL-1b) remotely on 2 high and 2 low stress days before and after the interventions. Because this pragmatic effectiveness trial of a live, online mindfulness- based intervention with naturalistic remote monitoring is already embedded in our safety-net health system, it can be implemented immediately and disseminated rapidly if effective at reducing depression symptoms, and could impact behavioral health systems nationally during and after COVID-19 and future public health crises.",2020,2021,Cambridge Health Alliance,696691,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C07167,3U54CA233465-03S2,Impact of COVID-19 on cancer care delivery among diverse populations,"The COVID-19 pandemic and concomitant lockdown across the US has forced sudden and unplanned changes in cancer patient care. A majority of cancer patients are older and immunocompromised while undergoing treatment, which presents a difficult challenge for oncologists and surgeons trying to decide how to continue the best care for their patients while minimizing the risk of infection with SARS-CoV-2. Simultaneously, the ability of patients to adhere to treatment recommendations, and to deal with cancer treatment induced side effects and various co-morbidities, has also been severely affected by the consequences of the COVID-19 pandemic. Many patients lost their usual infrastructure to handle their care, and many may have altered their behaviors towards treatment due to fear, lack of resources, or financial instability. The overall impact of ongoing changes in cancer treatment patterns, and changes in patient adherence to ongoing treatment due to COVID19 is yet to be defined. Early numbers from the American Cancer Society Cancer Action Network show that close to 80% of patients in active treatment for cancer experienced a delay in their healthcare, including 17% that reported to their cancer therapy. We propose to evaluate the impact of the COVID-19 pandemic on cancer care delivery among diverse populations, particularly those mostly affected by this outbreak, which include Blacks and Hispanics. We propose to identify and evaluate the impact of ongoing changes in cancer treatment, and changes in patient adherence to treatment among diverse populations, with the long-term goal of learning from this experience to better serve cancer patients moving forward as this pandemic continues its course. The pandemic imposed changes in cancer treatment protocols and survivorship follow-up to accommodate stay-at-home requirements, new hospital protocols to reduce infection rates, and for the protection of vulnerable cancer patients. Many of these changes may prove to be as effective as the standard of care, some may not. We propose to conduct a mixed-methods study within the Norris Comprehensive Cancer Center (NCCC) clinics, focusing on two of the priority cancers for our catchment area with high volume in our clinics: breast (BrCa) and lung cancer (LCa), focusing on identifying changes in cancer treatment for these two cancers from the start of the COVID-19 pandemic in March 2020 until September 2020, in comparison with the same time period in 2019 (Aim 1). We propose to identify treatment changes and evaluate their impact on short-term outcomes 12 months post-treatment. Given the diversity of our patient population, we are uniquely positioned to identify disparities in cancer treatment outcomes and adherence to treatment among minority populations, particularly Hispanics who constitute ~40% of our patient population. To enhance our reach and understanding of the impact of COVID-19 among Black cancer patients, we are leveraging the Florida-California Cancer Research Education and Engagement (CaRE2) Health Equity Center Community Outreach Core, which is focused on community outreach and engagement among Blacks and Hispanics in Florida and California, and will allow us to include a large Black patient population.",2020,2023,University Of Southern California,164784,Human Populations,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2018 +C07168,3P30CA008748-54S4,Role of host genetics in COVID-19 susceptibility and severity of infection,"Novel Coronavirus 2019 SARS-CoV-2 (COVID-19) infection is a global pandemic disease that has severely affected the United States. Emerging data suggests that racial and ethnic minority groups are disproportionately affected by COVID-19 and African Americans (AA) are overrepresented among hospitalized patients. The clinical symptoms vary from mild in approximately 80% of cases to critically ill. Established risk factors are age, gender and several comorbidities including cancer. Many other factors in clinical severity remain unexplained. This proposal will leverage remnant biospecimens from laboratory-proven COVID-19 positive individuals at Quest Diagnostics, a national commercial laboratory that has performed over 3.75 million COVID-19 tests and has identified over 298,000 positive cases to date, to study host-genetics of COVID19. We expect to include >7500 samples with whole genome genotyping, performed in collaboration with intramural NCI. While there are no established predictors of severity, certain biomarkers from total blood count have been observed to correlate with worse outcomes. Several studies have reported the role of uncontrolled cytokine release to be correlated with poor outcome. We will incorporate biomarkers such as lymphocyte count, neutrophil count and other inflammation markers to develop a severity score. Using this severity score, we will classify individuals as having mild, severe or critical infection. Biospecimens with de-identified clinical data from Quest and vital status data from the National Death Index in the 28 days period from testing positive, will be utilized to determine whether host genetic factors modify COVID-19 outcomes. We will discover novel genetic variation and clonal hematopoiesis (CH) associated with infection severity, mortality and cytokine storm. Finally, we will compare these novel genetic biomarkers in a cancer cohort of 2,000 individuals from MSKCC to contrast COVID-19 specific outcomes in cancer care. This study represents one of the largest COVID-19 cohorts for genetic association studies. These data will be used to compare genetic diversity and the role it plays in COVID-19 severity and will add to the understanding of constitutional determinants of host immune response to mild and severe viral infection and inflammation.",2020,2023,Sloan-Kettering Inst Can Research,177000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity,2020 +C07169,1U01CA260588-01,SARS-CoV-2-reactive tissue-resident memory T cells in healthy and cancer subjects,"PROJECT Summary: This multi-PI proposal titled ""SARS-CoV-2-reactivesubjects"" is written in response to 'RFA-CA-20-039' -tissue-resident memory T cells in healthy and cancerResearch projects in SARS-CoV-2 Serological Sciences.Recent studies have shown that antibody responses to SARS-CoV-2 infection decline rapidly over time, implyinga lack of durable protective humoral (B cell) immunity. Whether this is also true for cellular immunity (e.g., Tcells) is poorly understood. It is well established that CD8+ TRM cells are the first line of defense in viral infectionsat mucosal/barrier sites. They are also known to protect hosts against homologous or heterologous re-infections.Our group was the first to show that TRM cells are pivotal players in driving effective anti-tumor immune responsesin lung cancer, and that TRM cells are the primary cellular targets of anti-PD1 therapies. These key findings werepossible because of the ongoing collaboration between Dr. Vijayanand, Dr. Ay, and Dr. Ottensmeier (Multi-PI).This team brings together experience in T cell immunology, single-cell genomics, bioinformatics, and cancerimmunology. Our Multi-PI team has recently performed the first and largest single-cell RNA-seq and TCR-seqanalysis of SARS-CoV-2-reactive CD8+ and CD4+ T cells (~300,000 single-cells) from COVID-19 patients. Here,to understand TRM responses to SARS-CoV-2, we will capitalize on a cohort of cancer (n=100) and non-cancer(n=100) patients, who will provide excess airway (nasal, oropharynx, larynx), lung and tumor tissue specimensobtained during routine surgery. In AIM 1, we will define the properties of SARS-CoV-2 reactive TRM cells fromcancer and non-cancer patients with or without previous SARS-CoV-2 infection. We will perform combinedsingle-cell RNA-seq and TCR-seq analysis of CD8+ TRM cells in the airways (nasal, oropharynx), lung, and tumortissue. In parallel, by stimulating PBMCs with SARS-CoV-2 peptide pool, we will determine the transcriptomicand TCR sequence of SARS-CoV-2 reactive T cells. We will utilize this TCR sequence information to define thenumbers and properties of SARS-CoV-2 reactive-TRM cells in mucosal and tumor tissues. Recent studies in non-exposed individuals (pre-COVID-19 pandemic) indicate pre-existing, circulating CD8+ T cells, with humancoronavirus cross-reactivity. Here, we will measure the quantity and quality of pre-existing SARS-CoV-2 cross-reactive TRM responses in subjects without clinical or serological evidence of previous SARS-CoV-2 infection. InAIM 2, we will assess the impact of SARS-CoV-2 infection on anti-tumor and other anti-viral TRM responses. Wewill stimulate matched PBMCs (as above) with peptide pools targeting (i) common respiratory RNA viruses(influenza (FLU), RSV), (ii) persistent DNA viruses (CMV, EBV), and (iii) a tumor-driving virus (HPV) to definethe TCR sequence of the respective virus-specific and tumor(HPV)-specific CD8+ T cells; we will utilize the TCRinformation to determine frequency and properties of other virus/tumor-reactive TRM cells in mucosal and tumor-tissue cells.",2020,2022,La Jolla Institute For Immunology,1446305,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +C07170,3U54MD013376-02S2,RCMI@Morgan: Center for Urban Health Disparities Research and Innovation (2),"PROJECT Summary: Similar to HIV and hepatitis C virus, SARS-CoV-2, the cause of COVID-19, is most devastating to people ofhealth disparity populations (HDP). However, we hypothesize that COVID-19 could cause health disparitiesamong different HDP (i.e. ""disparities within"") and certain circumstances and determinants could contribute toand predict the ""disparities within"". Our ongoing partnerships with a multi-hospital healthcare system and amultisite community health center for the study of HIV/HCV-related health disparities provide an immediate,practical, and pertinent platform to study the impacts of COVID-19 on health outcomes and healthcare accessand utilization among people of various HDP. The hospitals of the healthcare system and the clinics of thecommunity health center are situated in urban, suburban, and rural areas with major health disparities. Thehealthcare system has provided SARS-CoV-2 testing services and treated many hospitalized COVID-19patients. The community health center provides HIV care to people of racial/ethnic and sexual/gender minoritiesand other vulnerable populations. We will take advantage of the ongoing partnerships, using a retrospectivecohort study design with data from the medical records, to dissect the ""disparities within"" caused by COVID-19.First, we will delineate the clinical features and natural history of COVID-19 among the hospitalized patients, anddetermine the factors associated with COVID-19 pathogenesis, disease severity, and treatment effectiveness.We also aim to establish novel, unique, and tailored clinical ""scoring"" systems/models that can be used to predictCOVID-19 outcomes and severity in patients of different HDP. Second, we will analyze the trends in andcharacteristics of the SARS-CoV-2 testing and assess whether people of the HDP were underrepresented in thetesting. We will also analyze the factors associated with SARS-CoV-2 positivity among those tested. For thosewho tested positive, we will assess their participation/engagement in the COVID-19 cascade of care anddetermine the factors associated with attending or missing each of the stages in the care cascade. Next, we willassess the HIV continuum of care during the COVID-19 lockdown, analyzing the trends and factors associatedwith missing appointments, labs, and/or prescriptions as well as the utilization of telehealth. We will also examinethe HIV-related health outcomes among those who continued care during the lockdown. Finally, we will performquestionnaire surveys or interviews to assess the experiences and perceptions of (1) COVID-19 patient carefrom the frontline healthcare workforce and (2) the pros and cons of telehealth in HIV care from the HIV patientsand care providers. We will also evaluate how the COVID-19 pandemic has changed/shaped the perception andcareer/specialty choice of the medical residents, interns, and students. The results from this project will helpreduce the health disparities caused by COVID-19 among the HDP.PROJECT SUMMARY",2020,2024,Morgan State University,188750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Disease pathogenesis | Approaches to public health interventions | Indirect health impacts,2019 +C07171,3R44CA246991-02S1,SAC-COVID: An FDA-approved Phase III clinical trial evaluating the safety and therapeutic efficacy of CD24Fc in severe COVID-19 patients,"Summary: Although most COVID-19 patients exhibit mild to moderate clinical symptoms, a substantial portion requirehospitalization with oxygen support. These patients are classified as having severe COVID-19 and have highrisk of progression to an intensive care unit (ICU) with requirement for invasive mechanical ventilation,extracorporeal membrane oxygenation (ECMO), and carry high risk for mortality. The current proposal seeksto repurpose CD24Fc, a first-in-class biological drug in cancer immunotherapy, to accelerate clinicalimprovement while reducing clinical progression of severe COVID-19 patients. The new drug belongs to thecategory of immunomodulators, and thus complements antiviral therapeutics that are being developed to inhibitSARS-CoV-2 virus replication. In addition to viral damage of lung epithelial cells, the pathogenesis of COVID-19 involves inflammation in response to cellular injuries caused by the virus, which is mediated byinflammatory factors referred to as damage-associated molecular patterns (DAMPs). The prototypical DAMPssuch as HMGB1 and HSP70/90 are released when cells undergo either stress or necrosis, and triggerinflammation by interacting with TLR4 or RAGE. Over 10 years ago, we showed that the CD24-Siglec 10/Gpathway selectively regulates inflammation to DAMPs. Numerous studies have confirmed the role of DAMPsin the pathogenesis of different viral infections. Recent reports from our group in collaboration with others havedemonstrated a critical role for CD24 and Siglecs in inflammation caused by human/simian immunodeficiencyvirus (HIV/SIV). Based on this new understanding, effective treatment of COVID-19 likely requires acombination of both antiviral and non-antiviral-based approaches. Antivirals can limit SARS-CoV-2 replication;while immune modulators can ameliorate inflammation in the lung, protect lung tissue from inflammatoryinjuries, preserve immune function by preventing T cell lymphopenia and functional T cell exhaustion, andprevent cytokine release syndrome (CRS). Given the biology of the CD24-Siglec pathway in limitinginflammation to DAMPs, we hypothesize that the CD24-Siglec innate-immune-checkpoint can be fortified totreated COVID-19 patients and improve outcomes for patients. CD24Fc is an investigational drug thatcomprises the non-polymorphic extracellular region of CD24, which we have shown to be an innate checkpointagainst the inflammatory response to tissue injuries or DAMPs, attached to the Fc region of human IgG1.Preclinical and clinical studies have demonstrated that CD24Fc effectively addresses the major challengesassociated with COVID-19 with excellent safety and therapeutic activity in leukemia patients with high risk ofgraft vs host diseases due to hematopoietic stem cell transplantation (HCT). Building on these excitingdevelopments, we received FDA approval of a clinical protocol for a Phase III clinical trial testing thetherapeutic effect of CD24Fc in protecting COVID-19 patients. The Phase III trial will involve 230 patientsrandomized into blinded CD24Fc arms and placebo, with time to clinical improvement from severe to milddisease and time to clinical progression as the co-primary endpoints. By showing safety and efficacy ofCD24Fc for COVID-19 treatment, our work will provide a new medical countermeasure for the global healthcrisis and potential new pandemic by emerging strains of SARS virus and influenza virus in the future. Therequested funding will cover the first part of the clinical trial that provides clinical proof-of-concept for CD24Fcin COVID-19 patients.",2020,2021,Oncoimmune Inc,1000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 3 clinical trial,2019 +C07172,3R01AG046149-07A1S2,Building Community Capacity for Disability Prevention for Minority Elders COVID-19 supplement,"PROJECT SUMMARYPrevious studies have shown that major health crises and economic shocks can have negative impacts onmental health, which are worsened when physical quarantine is required. A particularly vulnerable populationare those that have physical and emotional problems and are ethnic/racial and linguistic minority elders, manyof whom live in areas with high infection rates and lack of appropriate health resources. The ongoing impact ofthe crisis on minority elders, who may take longer to recover and require longer periods of quarantine, isessential to understand and address. Our proposed supplement extends from the Positive Minds StrongBodies clinical trial, that showed positive outcomes for this combined mental health and physical disabilitymanagement and prevention intervention. We seek to assess the long-term effect of this program in reducingelders' mortality (Aim 1) and maintaining mental health (Aim 2), as participants have been exposed to COVID-19 or its social effects. We hypothesize that elders who received the intervention approximately 3 years agopre-COVID will have a lower trend for mortality than those in the control condition, after adjusting for age,gender, and comorbidities at baseline. Our study is a unique opportunity to address disparities in a multiethnic,multilingual sample, including Latino, Asian and Black participants in 4 languages, Spanish, Mandarin,Cantonese and English. We propose to test whether the Positive Minds Strong Bodies intervention buffersmental health and disability impacts, through recontact of elders who participated in the 2015-2019 trial, alongwith those that will be newly enrolled in our new implementation study. In the third aim of the supplement, wewill explore the impact of the COVID-19 pandemic on daily stressors for ethnic/racial minority elders, as well astheir responses to public health interventions such as home confinement, social distancing and isolation, massrisk communications, disease testing, intention to vaccinate and contact tracing. The proposed supplement willtest the potential for this combined intervention to contribute to ongoing preparedness during the COVID-19pandemic while also providing an evidence-based program that could support a diverse population in the faceof future health crises.",2020,2025,Massachusetts General Hospital,209766,Human Populations,Asian | Black | Other,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2014 +C07173,3U54MD012388-04S5,Southwest Health Equity Research Collaborative (2),"PROJECT Summary: The novel coronavirus (COVID-19) has exacerbated health disparities throughout the United States (US) andimpacted American Indian/Alaska Native (AI/AN) populations in significant ways. Arizonahas the third largestpopulation of AI/AN in the US (over 350,000) and is home to 22 federally recognized sovereign Native nations.Compared with Whites, AI/AN in Arizona have a significantly higher prevalence of health risk factors thatincrease their susceptibility to COVID-19. AI/AN represent approximately 4.6% of the state's population, yetaccount for 19% of COVID-19 deaths where race and ethnicity of victims is reported. The long-term goal ofthis study is to conduct community-engaged research and outreach to increase COVID-19 awareness andeducation among AI/AN communities in Arizona disproportionately affected by COVID-19 and to reducemisinformation and mistrust. The goal of this Administrative Supplement is to establish effective, culturallyappropriate strategies to enhance participation of AI/AN communities in prevention and treatment of COVID-19, including vaccine trials and future vaccine uptake. This work will be guided by a community engagementframework, which emphasizes equitable participation between scientists and community members in allphases of the research. In partnership with AI/AN communities in the catchment area of the parent U54 RCMI:The Southwest Health Equity Research Collaborative (SHERC), we aim to: 1) Assess awareness,knowledge, experiences, concerns, attitudes, and needs regarding COVID-19 vaccine trials and vaccinationuptake among AI/AN communities in Arizona; 2) Develop and adapt culturally-appropriate educationalmaterials and strategies designed to increase awareness of COVID-19 vaccine trials, decrease misinformation,and increase medical trust; and 3) Implement the educational session and evaluate the impact of educationalmaterials and strategies on enhanced awareness, trust, self-efficacy, and willingness and intent to participatein COVID-19 vaccine trials and future vaccines. There is an urgent need to better address the concerns ofAI/AN communities at this critical juncture of the COVID-19 pandemic in Arizona. Knowledge derived from thisstudy has the potential to build awareness about COVID-19 vaccine trials and enhance participation amongAI/ANs in the trials and future vaccine uptake. The unique geographical and cultural setting of SHERC,combined with the experience and expertise of this interdisciplinary team of investigators, well-positions theproposed study for success.",2020,2022,Northern Arizona University,200000,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2017 +C07174,1U54CA260543-01,North Carolina Seronet Center for Excellence,"Abstract.The UNC Center for Excellence in SARS-CoV2 Serologic Research uses basic and applied researchstrategies to improve our understanding of the molecular and cellular mechanisms driving serological andhumoral immune responses after SARS-CoV2 infection. Our overall goals are to 1) characterize the immuneresponses elicited to SARS-CoV2 infection, 2) understand the mechanisms driving the serological, humoral andcellular immune responses, 3) determine modifiers of the serologic memory and 4) determine the serologicalcorrelates of disease pathogenesis, and protection against future infection. The program includes threeResearch Projects led by internationally renowned exerts in coronavirus emergence, pathogenesis and immunity(Project 1: Baric), clinical and translational mucosal and systemic immune correlates of disease (Project 2:Bartelt & Margolis) and host-pathogen interactions driving innate and serological immunity (Project 3: Wallet& Maile). Program-wide support is provided by an Administrative Core A and two Shared Resource Cores B andC. Core A includes a robust infrastructure for programmatic oversight as well as participant recruitment, samplecollection, tracking and sharing (Core A: Baric & Wallet). Core B is led by world renowned experts incharacterization of human antibodies in protection and pathogenesis of disease (Core B: de Silva &Lakshmanane) and will provide recombinant spike protein antigens from SARS-CoV-2 as well as antigen-specific serological assays required for accomplishing the aims of all three Research Projects. Core C is led byserological experts (Core C: Ippolitto, Georgiou & Lavinder) who have revolutionized techniques tocomprehensively analyze the molecular composition of the serological antibody repertoire (IgG and IgA) and thecellular antibody repertoire (i.e. B cell receptor) and thus will delineate these repertoires in and isolate humanmonoclonal antibodies from SARS-CoV-2+ individuals in cohorts defined in each Research Project. All threeResearch Projects are integrated, and each require the support of all three Cores. To this end, Project 1 willcharacterize the breadth and potency of polyclonal neutralizing antibody responses as well as determine thekinetics, magnitude and durability of the type-specific and cross neutralizing responses in both the systemic andmucosal compartments. Project 2 will determine the durability and the breadth of anti-SARS-CoV-2 serumantibodies and memory B-cells generated among convalescent plasma donors as well as determine the effectof convalescent plasma on the innate, adaptive and antibody repertoire in recipients. Project 3 will reveal innateimmune signatures as a function of serology across the span of natural disease, as well as identify signatureswhich promote development of protective vs. pathogenic antibody repertoires, while delineating mechanisms ofantibody mediated activation and suppression of innate immune function which drives severe vs. mild diseaserespectively. The integrated expertise of our Team is necessary and sufficient to address the novel cross-cuttinghypotheses put forth which will improve our understanding of SARS-CoV2 serological and humoral immunity.",2020,2022,University of North Carolina at Chapel Hill,3974612,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C07175,1U01CA260476-01,Immunologic Signatures of SARS-CoV-2 Vaccination and Disease,"Abstract: The development of a SARS-CoV-2 vaccine may be critical to ending the COVID-19 pandemic. However, acritical gap in knowledge is the lack of understanding of correlates of SARS-CoV-2 immunity in humans.Our preliminary data suggest that antibodies correlate with protection following vaccination in nonhumanprimates and that unique antibody functional profiles appear to predict disease outcome in natural infection inhumans. Our data also point to a converging antibody profile, including both the antigen-binding domain drivingneutralization and Fc-mediated effector functions driving protective immunity. Another gap in knowledge is theunknown durability of protective immunity following SARS-CoV-2 infection and vaccination in humans.Our preliminary data suggest that antibody titers may wane quickly following SARS-CoV-2 infection in humans,but larger studies and longer follow-up are needed to define the kinetics of antibody responses in convalescentindividuals. Moreover, the durability of vaccine-elicited antibody responses remains to be determined.We hypothesize that both convalescent and vaccinated humans will develop the functional antibodysignature that correlates with vaccine protection against SARS-CoV-2 challenge in rhesus macaques.We further hypothesize that vaccination will induce antibodies with greater durability than those inducedby natural infection and that an immunologic correlate of durability can be defined.Specific Aim 1. Define the antibody profiles following SARS-CoV-2 infection or vaccination that correlatewith protection. We will dissect the functional antibody responses elicited in SARS-CoV-2 infected individualsand in SARS-CoV-2 vaccinated individuals to provide insight into correlates of protection.Specific Aim 2. Define the immunologic correlates of durability of SARS-CoV-2 antibody responsesfollowing infection or vaccination. We will compare the durability of antibody responses induced in SARS-CoV-2 infected and vaccinated individuals, and we will define an immunologic correlate of durability.",2020,2022,Beth Israel Deaconess Medical Center,1477970,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +C07176,1U01CA260462-01,Adaptive Immunity and Persistent SARS-CoV-2 Replication,"Project Summary/Abstract: The pandemic caused by the novel coronavirus, SARS-CoV-2 (SARS2) has so far infected greater than3.5 million individuals and resulted in >138,000 deaths in the US. Although it has been suggested thatadaptive immunity plays an important role in improving clinical outcomes of patients infected withSARS2, protective immune responses have not been specifically defined. Also, the variability in clinicaldisease and outcome in patients with SARS2 infection has not been explained based on qualitative andquantitative antiviral immune responses. Interestingly, a significant proportion of children with presumeddeficits in immune competence secondary to cancer chemotherapy and hematologic disorders havebeen observed to shed virus from the upper respiratory tract for prolonged periods of time (>4 weeks),even after complete resolution of clinical symptoms. This finding raises the possibility that specificqualitative or quantitative deficits in adaptive immune responses in some individuals can result inincomplete control of virus replication and prolonged virus shedding. Therefore, an understanding of theimmune responses that lead to control of virus shedding could help define correlates of protectiveimmunity and perhaps more importantly, determine the potential value of vaccines to limit spread ofSARS2 to unvaccinated populations. The major goal of our studies is to quantify adaptive immuneresponses to SARS2 in a cohort of children with varying levels immune responsiveness and to relatethese responses to the control of virus shedding in the upper respiratory tract, thus allowing stratificationimmune reactivity and control of virus replication. Defining relationships between variations in immunecompetence and virus shedding could provide novel insight into the level and nature of adaptiveimmunity, more specifically antiviral antibodies, that can restrict or eliminate viral shedding in SARS2infected patients. Our studies will also identify SARS2 variants that arise during poorly controlled virusreplication in these patients as prolonged virus replication coupled with ineffective immunity offers anideal opportunity for the generation of viral variants. Analysis of these variants in terms of the quality andquantity of SARS2 antibody responses will help elucidate the role of SARS2 sequence variation andpersistent virus replication as a mechanism for prolonged virus replication. Together, these studies willtest our hypothesis that variations in immune responsiveness contribute to prolonged viral replicationand shedding.",2020,2022,University Of Alabama At Birmingham,1182648,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C07177,3U54MD011240-05S1,"Community Organizations for Natives: COVID-19 Epidemiology, Research, Testing, and Services (CONCERTS)","Abstract: As the COVID-19 pandemic spreads to every corner of the US, the plight of urban American Indian/AlaskaNative (AI/AN) people is often overlooked or ignored. SARS-CoV-2 and the disease it causes, COVID-19,disproportionately affect AI/ANs, who are at highest risk of any US racial or ethnic group for developing severedisease and dying from COVID-19. Sadly, we have no data on infection rates, morbidity, or mortality on urbanAI/ANs, who comprise 71% of the total AI/AN population. Urban AI/ANs may obtain clinical care through UrbanIndian Health Programs (UIHPs), the Indian Health Service, tribal, public, and private facilities. Our discussionswith UIHP leaders reveal complex barriers to testing, such as inability to procure test kits, reach homeboundpatients, and inadequate staffing for outreach. To increase SARS-CoV-2 testing among urban AI/ANs, we willdraw on a nationwide network of Satellite Centers (all led by AI/AN scholars) established in 6 large NIH-sponsored initiatives that reach, engage, and ensure participation of community stakeholders in research at thelocal level. Our Satellite Centers will partner with 6 geographically contiguous UIHPs across the US to launchthe ""Community Organizations for Natives: COVID-19 Epidemiology, Research, Testing, and Services"" study(CONCERTS). The goal of CONCERTS is to remove barriers and increase SARS-CoV testing among urbanAI/ANs. First, we will use data from these 6 UIHPs to estimate current uptake of SAR-CoV-2 testing and theburden of COVID-19 disease. Second, we will survey clinic administrators, providers, and 600 patients acrossall 6 UIHPs to understand testing barriers and promoters, and preferred testing options. Third, informed bythese data, the 6 UIHPs will implement locally tailored clinic-associated (e.g., drive-through, mobile unit-basedtesting) and outreach-based strategies (e.g., COVID-19 navigators) to increase SAR-CoV-2 testing. After 1year, we will re-examine testing rates for a pre-post comparison to establish if these strategies weresuccessful. Fourth, we will collaborate with the UIHPs to produce a list of sustainable, pragmatic practices forfuture pandemics and vaccination programs. Our primary outcome is the monthly testing rate for SARS-CoV among urban AI/ANs. The Specific Aims are to: 1) Estimate baseline SARS-CoV-2 testing and infectionrates to identify disparities in testing and disease burden in urban AI/ANs; 2) Survey administrators, providers,and 100 patients from each of 6 UIHPs to identify barriers, facilitators, attitudes, risk factors, and necessaryservices pertinent to SARS-CoV-2 testing; 3) Implement clinic-associated and outreach-based strategies ateach UIHP to increase testing rates and reduce spread of SARS-CoV-2, then compare testing rates before andafter implementation; and 4) Evaluate CONCERTS and catalog pragmatic practices for application to futurepandemics and successful vaccination campaigns among urban AI/ANs. The nation's efforts in AI/AN healthcare have been described as a ""historic failure."" This history continues during the current pandemic,underscoring the urgent needs of facilities serving America's ""largest tribe"" - urban AI/ANs.",2020,2022,Washington State University,3261570,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication,2020 +C07178,3R01EB022230-04S1,Image-Guided Drug Delivery for Pancreatic Neuroendocrine Tumor,"Project Summary/Abstract (limit within 30 lines) The COVID-19 emerged in December 2019 and then spread rapidly over 214 countries. As of May 15, 2020,a total of more than 4.5M confirmed cases and over 300,000 deaths have been reported worldwide, posingsignificant health and economic threats to our society. Currently, an array of drugs approved for other indicationshave been studied, in addition to multiple investigational agents, for the treatment of COVID-19. Antiviralsincluding remdesivir, favipiravir, chloroquine, and hydroxychloroquine have been rapidly tested in these clinicalstudies and demonstrated preliminary efficacy against COVID-19. However, these studies also revealed that aproportion of patients receiving remdesivir had significant adverse effects, including multiple-organ dysfunctionsyndrome, septic shock, and acute liver and kidney injury. Similarly, the use of chloroquine andhydroxychloroquine in COVID-19 patients has raised serious safety concerns including arrhythmias,cardiomyopathy, and retinopathy. These adverse effects are related to their wide distribution of drugs in thewhole body after administration, causing damages in off-target vital organs. Therefore, tissue-specific deliveryof antiviral therapeutics would ameliorate adverse effects while maintaining their efficacy to treat COVID-19. Our hypothesis that renal clearable ultrasmall nanocarriers can payload antiviral drugs selectively and deliverthem to treat COVID-19 with reduced side effects. In our parent R01 (NIBIB #R01EB022230), we havedeveloped ultrasmall nanocarriers for targeting, imaging, and image-guided surgery of pancreaticneuroendocrine tumors. Importantly, over 80% of the unbound dose was ultimately eliminated into the urinewithin 24 h post-injection after systemic circulation. This narrows the design of nanocarriers to include a targetinganchor, an imaging moiety, and a distribution domain, and we have worked diligently to create a reciprocalarrangement whereby each chemical composition provides balancing properties to the others. Interestingly,during the evaluation of inclusion complexation, we found that the nanocarriers can deliver other types of drugsincluding imatinib (Kang et al. Adv Mater, 2020). This result suggests that ultrasmall nanocarriers can alsodeliver antiviral drugs to the target with reduced side effects due to rapid renal clearance of unbound molecules. Therefore, the ultimate goal in this administrative supplement application is to develop ultrasmallnanotherapeutics that are complexed with antivirals to treat COVID-19. By payloading selected antiviral drugsinto the ultrasmall nanocarriers, we will be able to achieve image-guided drug delivery to the respiratory systemwith reduced side effects due to the rapid renal clearance of unbound drugs. To achieve this goal, we propose1) to develop renal clearable nanocarriers for antiviral drug delivery and 2) to evaluate the pharmacodynamicsand therapeutic efficacy of the nanocarriers in mouse models of coronavirus infection. Armed with the near-infrared fluorophores conjugated on the nanocarrier, we will also monitor the biodistribution and clearance ofantivirals as well as their targetability and therapeutic efficacy under the real-time imaging system.",2020,2021,Massachusetts General Hospital,651080,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2017 +C07179,3R33AG057395-04S1,Use of Behavioral Economics in Repeat SARS-CoV-2 Antibody Testing in Disadvantaged Communities,"Abstract: The rapid spread of the SARS-CoV-2 virus has greatly impacted underserved populations. Thisproject aims to understand social and behavioral determinants of COVID-19 testing andvariations within sub-groups of this population. In partnership with the largest federally qualifiedhealth center in the United States, we will collect survey data and conduct a randomizedexperiment on 2,160 individuals (540 families) to evaluate the effectiveness of risk-basedmessaging and incentives that promote repeated testing for SARS-CoV-2 antibodies. In a 2 x 2(Messaging x Incentive) factorial experiment, participants complete a comprehensive set ofsocial and behavioral surveys to identify determinants of commitment to testing. They are thenrandomized by strata identified in the survey to receive personalized messaging promotingrepeated testing. Messaging will focus upon either (1a) their household risk or (1b) theirpersonal risk of COVID-19. They are also randomly assigned to either an incentive conditionthat (2a) insures against losing baseline rewards for initial testing, or (2b) that enters them into alottery with a small chance to win $100 if they complete both tests. Both the insurance andlottery conditions carry the same incentive costs. Our previous work in similar populationsdemonstrated that adherence to planned health behaviors is higher with insurance-basedincentives than cash payments of equal value. This experiment compares insurance-basedincentives to lottery incentives that have been shown to be effective in multiple contexts. Finally,we evaluate if social and behavioral determinants of health result in heterogeneous treatmenteffects that can inform customization of incentive offerings in future programs devoted toincreasing uptake of testing or vaccinations among underserved populations.",2020,2022,University Of Southern California,648399,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C07180,1U01CA260507-01,Immuno-Serological Assays for Monitoring COVID19 in Patients with Hematologic Malignancies,"SUMMARYPatients with hematologic malignancies appear to have a higher risk of SARS-CoV-2 infection. Diseasecourses are variable in severity, influenced by immunosuppression due to the malignancy and its treatmentdetermining the degree of immune-mediated hyperinflammation implicated in lung damage, multi-organ failure,and death. This highlights the need for comprehensive clinical tests to monitor COVID19 patients, specifically,with hematologic malignancies. We propose to develop and validate two novel immuno-serological assays thatwill be deployed to conduct longitudinal measurement of plasma markers and peripheral blood immune cellsfrom COVID patients with different hematologic malignancies. First, we will develop an automated 32-plexedplasma protein assay to quantify SARS-COV-2 IgG/IgM antibodies, cytokines/chemokines, angiogenesismarkers, endotheliopathy markers, and pro-thrombotic markers all combined in a high-density antibodybarcode array microchip. Second, we will develop a microchip assay for single-cell immune functionmeasurement to quantify cell types and 30+ immune effector proteins in peripheral blood immune frompatients. Single-cell transcriptome sequencing will be performed on select samples to cross-validate the resultsand reveal the mechanisms of action in COVID-induced immune activation. Third, these new assays will bedeployed to measure a cohort of COVID19 patients with or without hematological malignancies and healthydonors in order to identify potential molecular correlates with immune-mediated pathology and COVID diseaseseverity uniquely in hematological cancer patients. As the COVID19 vaccines become available, we will applythese assays to monitoring vaccine-induced humoral, cellular, and immunological response in hematologicalcancer patients and compare to non-cancer populations to understand differences and ways to improve thesuccess of vaccination in patients with hematologic malignancies - a vulnerable group of patients who may notfollow the same mechanisms as general populations in COVID19.",2020,2022,Yale University,1423746,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Immunity | Disease models | Disease susceptibility | Prognostic factors for disease severity,2020 +C07181,3R01HG005115-12S1,High Accuracy Nanopore Sequencing,"This project is an expansion of the scope of our current funding which was awarded to improve nanoporesequencing. In the course of our research to improve nanopore DNA sequencing, we have discovered anddeveloped a new high-resolution single-molecule tool to observe the motion of helicases and polymerases. Thetool, which we called Single-molecule Picometer Resolution Nanopore Tweezers (SPRNT), is able to reveal thesingle-nucleotide steps of helicases and polymerases at unprecedented detail. These enzyme steps are so small(~0.3 nm) and fast (~ 1 ms) that no other existing single-molecule technique can resolve such motion in real timeand at physiological conditions. The genome of the SARS-CoV-2 virus encodes for an RNA-dependent RNApolymerase, also known as non-structural protein 12 (nsp12), and a superfamily 1B helicase, known as nonstructural protein 13 (nsp13). Both of these enzymes are essential and specific to the in vivo replication of manyviruses, making this genomic replication machinery an ideal drug target. Several drug candidates to inhibit theseenzymes exist, however, none are as effective as they need to be to stem the tide of the current pandemic. Manyquestions remain about how exactly these drugs interfere with the function of nsp12 or nsp13. SPRNT providesan opportunity to answer these questions. We aim to use SPRNT to analyze the single-molecule motion of nsp12and nsp13 in physiological conditions and in the presence of drugs against them. The exact knowledge of themechanisms by which various drugs inhibit nsp12 or nsp13 will enable more rational and rapid design of effectiveantiviral drugs that have the potential to stop COVID-19.",2020,2021,University Of Washington,313632,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2009 +C07182,3U54MD007601-34S2,Community Driven Approach to Mitigate COVID 19 Disparities in Hawaii's Vulnerable Populations,"PROJECT SUMMARY/Abstract: The long-term goal of this proposal is to eliminate COVID-19 disparities among Hawaii's racial/ethnically diverseyet vulnerable populations including Native Hawaiian and other Pacific Islanders (NHPI) living in rural andunderserved communities by integrating innovative SARS-CoV-2 testing capacity with novel community-specificmessaging and education. Compounded by long-standing health disparities and socioeconomic challenges,NHPIs suffer from increased infection and mortality rates attributed to COVID-19. To date, NHPIs rank amongthe highest disproportionately burdened by SARS-CoV-2 in the U.S. With the nation's highest Rt, a basicreproductive metric indicating the degree of viral spread, Hawaii's disaggregated NHPI data reveal furtherdisparities. Preliminary testing data collected by our partner, the Waianae Coast Comprehensive Health Center(WCCHC), Hawaii's largest federally funded community health center, indicates a significant deficiency in testinguptake, especially among Pacific Islanders. Further, we observed under-representative coverage of testingamong youth (ages 5-19 years old) in NHPI communities, despite their higher than average infection rate. Otherfactors, including slow testing turnaround time and untested asymptomatic cases, complicate efforts to containfurther community spread. Given the looming public health concerns around re-opening businesses and schools,these gaps highlight the critical need for innovative approaches of effecting behavioral change coupled withnovel testing strategies to enhance access to all community members, including school-aged children/youth.Fortunately, our partnerships in Hawaii's culturally diverse populations offer a unique opportunity to augment thecurrent COVID-19 response with community knowledge and resilience. We propose the hypothesis thatcommunity-contextualized messaging disseminated by novel healthcare-school partnerships coupled with arobust community and patient-centered testing strategy will increase reach, access, uptake, and impact forCOVID-19 testing in vulnerable populations. To test this hypothesis, our multidisciplinary team aims to (1)evaluate SARS-CoV-2 testing data, identify gaps and barriers in testing, and augment community testingcapacity to increase uptake and (2) optimize and implement community-informed COVID-19 messaging andeducation with a novel community healthcare-school network partnership in the NHPI population across Hawaii.Building on our parent ""Ola HAWAII"" grant, this project leverages our existing Community Engagement,Biostatistics, and Administrative Cores with NHPI partnerships to augment the RADx-UP Coordinating and DataCollection Center for common evaluation metrics on COVID-19 testing-related outcomes and implementation.This will lay the foundation for an engaged community network primed for disseminating anticipated vaccines inHawaii's highest risk populations. Given the urgency to both improve public health safety and re-opening schools,results from this project may offer insights into an integrated model or toolkit from which health clinics and schoolsin underserved & vulnerable communities across the country might actively participate in abating this pandemic.",2020,2022,University Of Hawaii At Manoa,3400883,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2020 +C07183,3R01DA043409-04S2,Integrating Assisted Partner Services and Phylogenetics for HIV and HCV Prevention,"Abstract: In sub-Saharan Africa and globally, many persons who inject drugs (PWID) are living with undiagnosed oruntreated HIV, experience high levels of poverty, food and housing instability, and discrimination, and haveincreased risk for health conditions that contribute to worse outcomes from COVID-19. It is also more challengingfor PWID to access healthcare when services have been limited by lockdowns and measures to ensure socialdistancing to prevent spread of respiratory viruses, such as SARS-CoV-2. We propose to recruit and follow acohort of 500 HIV-positive and 500 HIV-negative PWID and their partners, many of whom also have hepatitis C,to determine whether poorly controlled HIV infection, active drug use and other HIV- and PWID-specific riskfactors result in increased likelihood of COVID-19 acquisition, viral transmission, symptomatic disease andpoor clinical outcomes (AIM 1). We will also define transmission dynamics through phylogenetic analysesof SAR-CoV-2 sequences from symptomatic PWID (AIM 2) and determine whether HIV care and harmreduction service delivery disruptions are associated with poor compliance to ART and methadone, HIVviremia and other adverse outcomes (AIM 3). Our proposal is innovative in how it reaches PWID and partnersusing peer educators, employs targeted testing and symptom screening in this high-risk Kenyan population, anddefines COVID-19 transmission within and beyond local networks using phylogenetics. Participant recruitmentand enrollment will take place in drop-in centers and methadone clinics in Nairobi, Mombasa and Kilifi, Kenyaand follow-up visits will occur monthly for 6 months. In addition to collecting interview data and blood for SARS-CoV-2 antibodies, we will ask participants who have symptoms consistent with COVID-19 at any of the 7 visitsto self-collect a nasal swab specimen for SARS-CoV-2 polymerase chain reaction (PCR), followed by genomesequencing if positive. Laboratory assays for antibody and viral PCR testing will be conducted in Nairobi andpositive specimens will be shipped to Seattle for sequencing and phylogenetic analysis. We anticipate that ourresults will highlight the need for targeted testing among PWID and inform interventions and programs for HIVand addiction care and treatment across the globe for similar marginalized populations when confronted withCOVID-19 and other public health crises.",2020,2022,University Of Washington,152199,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Africa,Africa,,,,Kenya,Kenya,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2017 +C07184,1U54CA260560-01,Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses,"OVERALL Abstract: The overarching research theme for the Mount Sinai U54 Serological Center of Excellence ""Vulnerability ofSARS-CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses,"" is to fill the vital knowledgegap in factors contributing to the great vulnerability of lung cancer patients to morbidity and mortality from SARS-CoV-2 infection through serological analysis of antibody responses and studies of inter-individual variation inpatient-derived lung tumor and epithelial cells to SARS-CoV-2 infection. We will characterize and compare lungcancer patients' antibody responses to SARS-CoV-2 infection or SARS-CoV-2 vaccines with a matched non-lung cancer control group; quantitate differences in SARS-CoV-2 viral replication in lung cancer and normal lungepithelial cells from different lung cancer patients; and quantitate differences in neutralizing antibody responsesin lung cancer patients. This information is urgently needed to enact vaccine and other strategies for protectinglung cancer patients against development of COVID-19. While antibodies, induced by infection or vaccines, areprotective against many viruses, it has not yet been established if antibodies to SARS-CoV-2 are protective, howmuch and what types of antibody are needed for protection, and how long protection will last are unknown.Likewise, we do not know if lung cancer patients can mount an effective immune response and if different aspectsof lung cancer or its treatment influences this immune response. Our overall hypothesis is that lung cancerpatients have a different (e. g. weaker) antibody response to SARS-CoV-2 infection compared to persons withoutlung cancer, and that their lung cancer or lung epithelial cells play a role in viral replication of host responses,which together could explain the aggressive course and high fatality rate demonstrated in lung cancer patientswith COVID-19. Our U54 will determine whether natural infection or SARS-CoV-2 vaccines (forecast fordeployment) will give comparable serological antibody responses longitudinally in 1,000 lung cancer patientsand a matched non-lung cancer control group (1,000 individuals); and determine if there are differences inantibody responses related to age, gender, tobacco history, and race/ethnicity. The U54 proposal has twoProjects and three Cores (Administrative, Clinical, and Data Sciences). Project 1: ""Characterization of theAntibody Response to SARS-CoV-2 in Lung Cancer Patients"" quantitatively characterizes anti-SARs-CoV-2antibody responses and their functionality longitudinally in lung cancer patients compared to a control populationafter natural infection and vaccination, and relates the serological response characteristics to key clinical,demographic information. Project 2: ""Susceptibility of Lung Cancer Cells to SARS-CoV-2 Infection and Antibody-Mediated Neutralization,"" determines the inter-individual variation in lung cancers and lung epithelial cells tosupport SARS-CoV-2 viral replication, the inter-individual variation of antibodies to neutralize viral infection, andhow these host viral responses relate to host cell characteristics and important clinical demographic information.",2020,2022,Icahn School Of Medicine At Mount Sinai,3968419,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity,2020 +C07185,3U54GM104942-05S3,Developing novel strategies to increase COVID-19 testing among underserved and vulnerable populations in West Virginia through community and state partnerships,"West Virginia (WV) is rated by Becker's Hospital Review as the state with the sixth most vulnerable populationto the novel coronavirus (SARS CoV-2) while a second group at Wallethub, using three key domains (medical,housing, financial), rates WV as the most vulnerable state to SARS CoV-2 impact. Central to the state's extremevulnerability is the high prevalence of obesity, cardiovascular disease including hypertension, chronic lungdisease due to smoking and environmental exposure (e.g., mining), diabetes mellitus, and cancer. Additionally,WV is among the three states having the highest proportion of persons > age 65 years (20%). Through schooland university closures in March 2020, along with shutdown of non-essential businesses, WV had relatively fewCOVID-19 cases and deaths until July 2020 when transmissibility (Rt) skyrocketed. Testing remains problematicin WV for multiple reasons, including inadequate testing supplies, accessibility to testing sites (given the ruralityof the state and lack of widespread public transportation), shortages of personal protective equipment for staff,and lack of insurance coverage for surveillance testing and for uninsured persons. The West Virginia Clinicaland Translational Science Institute (WVCTSI) is submitting this application in partnership with multipleorganizations with which they have existing collaborative relationships, including: 1) the WV Practice BasedResearch Network (PBRN), a 107 site primary care network spanning the state, 2) the WV Department of Healthand Human Resources, 3) the WV National Guard, 4) West Virginia University (WVU) Health Sciences Centerand College of Engineering, and 5) the Partnership of African American Churches (PAAC). Critically importantis the generous match of $1.5 MM that the state of WV is offering to this initiative should this supplement receivefunding. Vulnerable populations addressed in the application include individuals in rural communities and AfricanAmerican populations as well as those with comorbidities known to increase risk of severe COVID-19. Given thehigh prevalence of substance use disorder (SUD) in WV, a cross-cutting theme is ensuring persons with SUDare included in all proposed strategies to increase SARS CoV-2 testing. We will address COVID-19 testingdisparities through achievement of the following specific aims, all of which use nucleic acid polymerase chainreaction testing on nasal or nasopharyngeal swabs: 1) Enhance COVID-19 testing among rural primary careoffices located across WV, 2) Intensify COVID-19 testing through mobile vans in areas forecasted to experiencea near-term increase in COVID-19 incidence, and 3) Increase COVID-19 testing in Black or African Americancommunities through a dedicated mobile van and home testing. Evaluation of implemented strategies includesassessing numbers of tests performed, uptake of home testing, satisfaction surveys, and structured interviewsamong Black or African Americans enrolled in the home testing study.",2020,2022,West Virginia University,3103241,Human Populations,Black | Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C07186,3R01HG009979-17S1,Cytoscape: A Modeling Platform for Biomolecular Networks,"This application is being submitted in response to NOT-HG-20-030. We will use data-driven network andhierarchical modeling techniques enabled by Cytoscape ecosystem tools and resources to build models ofSARS-CoV-2 infection and will use the models to propose mechanisms of variance in host response based onthe analysis of population genetic and COVID-19 disease outcome data. These data-driven models will informresearch in population risk stratification and potential COVID-19 therapies. Our models, analysis results, andtoolset will be made available to the research community via a website and data repository. The models will bederived from molecular and genetic interaction data and will be used to analyze population data onSARS-CoV-2 infection, comorbidities, and clinical outcomes currently being collected by the UK BioBank. Theanalysis will be updated periodically with each release of data, maintaining an up-to-date resource for theresearch community. The modeling tools and pipelines will be user-friendly and well-documented, enablingresearchers to build alternative models or to analyze other population data.",2020,2021,University Of California-San Diego,179529,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C07187,3U01HG008685-05S1,Finding Genomic Profiles of COVID-19 Phenotypes from the EHR,"Abstract: As the world searches for effective treatments and potential cures for the COVID-19 pandemic, theability to consolidate data, insights, and expertise from many disparate sources will be key to fullyunderstanding the patient outcomes of the infection. Key to facilitating this type of research is a cohesive andsecure research environment that enables clinicians, researchers, data scientists, and technologists frommultiple organizations to work together with a common goal of better understanding COVID-19 symptoms,associated risk factors, and successful therapies. Building upon faculty, staff and infrastructure already in placethrough the eMERGE IV Clinical Center at Mass General Brigham, we are proposing the creation of a COVID-19 Biobank Portal to provide a foundation for building a truly collaborative environment that is compliant withpatient privacy and offers a common set of bioinformatic tools and a standardized IT approach for the stagingof data and analyses. We will do this by accomplishing the following three Specific Aims which supplement theparent grant's Aim I which is: ""Polygenic risks scores will allow us to stratify eMERGE participants based ongenetic risk for common complex traits"" which will focus in this supplement on risk factors for severity ofCOVID-19 illness in our biobank participants. We propose to build on our expertise to accomplish the specificaims: Aim 1: We will create a COVID-19 Centric Biobank Portal that allows general institutional use withproper research agreements in place where patient cohorts can be studied using easily assessable andtransformed data and through which genomic samples can be obtained. Aim 2: Supplement the COVID-19Biobank Portal with test results, phenotype risk factors, symptoms, and outcomes for COVID-19 which arederived from data in the electronic health record (EHR) by using natural language processing andcomputational phenotypes and by performing chart reviews to validate severity indices and clinical outcomesfound in COVID-19 infected patients. Aim 3: Genetic data (array and sequence data) will be contributed to theeMERGE IV network and to the International l COVID-19 Host Genetics Initiative (https://covid19hg.org) suchthat data can be used to calculate polygenic risk scores (PRS) for genome-wide association studies of riskphenotypes and patient outcomes and polygenic risk scores (PRS) for COVID-19 outcomes in our dataset andin collaborations with others.",2020,2025,Brigham And Women'S Hospital,401928,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2015 +C07188,3U54MD013368-02S2,Health Disparities Research at UCR,"ABSTRACT Health literacy is a significant barrier for SARS-CoV-2 vaccine acceptance, particularly among low-income and minority communities that have experienced disproportionately high rates of COVID-19 infectionand mortality. Previous research has identified the importance of trust for health literacy. This is especiallytrue for minority communities that have experienced systemic discrimination within the US healthcare systemand harbor longstanding mistrust of physicians. Vaccine acceptance relies on public trust not only in individualproviders, but also in public health officials and the health care system as a whole. Public health experts agreethat the US lacks vaccine readiness and that interventions are needed to effectively overcome substantialvaccine hesitancy. Yet tens of millions of U.S. adults are unable to make decisions in their own best interestbecause they neither can access, nor understand, health information. This project uses a social ecological framework to investigate how low-income Latinx/Hispanics andAfrican Americans in Southern California's Inland Empire engage with health information about COVID-19and the SARS-CoV-2 vaccine. Understanding how information works as a system, rather than as a problemof physician-patient communication, facilitates identification of high-leverage points for communicationinterventions to increase vaccine acceptance among vulnerable populations. Research questions: What are the health information-seeking patterns of low-income and minoritypatients? And what can be learned from these patterns to design effective communication interventions tomitigate misinformation and overcome vaccine hesitancy? Aim 1: Investigate current information needs, knowledge, and concerns regarding COVID-19and a SARS-CoV-2 vaccine. Focus groups and a Community Advisory Board will inform the design of anonline survey to assess low-income African Americans' and Latinx/Hispanics' knowledge, beliefs,expectations, concerns, and fears regarding COVID-19 and a SARS-CoV-2 vaccine. Follow-up phoneinterviews will be conducted with a subset of survey respondents to probe more deeply into the processesthrough which individuals seek and obtain health information. Aim 2: Develop communication interventions to increase vaccine acceptance. Qualitative andquantitative analyses from Aim 1 will be integrated to categorize information-seeking patterns and identifyrelationships of trust in low-income minority communities. Communication strategies will then be designed toacknowledge both information barriers and existing social capital that can be harnessed in low-income andminority communities to increase vaccine acceptance.",2020,2024,University Of California-Riverside,199526,Human Populations,Black | Other,Unspecified,Urban Population/Setting,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2019 +C07189,1U01CA260469-01,Culturally-targeted communication to promote SARS-CoV-2 antibody testing in saliva: Enabling evaluation of inflammatory pathways in COVID-19 racial disparities,"Project Summary: African Americans develop and die from SARS-CoV-2 infection more than any other racial group in the UnitedStates, including in majority African American cities such as Flint, Michigan. SARS-CoV-2 disparities stem frommany interconnected causes. Yet, connections to inflammatory biological processes in COVID-19 disparitiesremain largely unknown. Evaluating inflammatory responses can be facilitated by SARS-CoV-2 antibodytesting, which can be used to identify and compare inflammation among those with and without confirmedSARS-CoV-2 infection, and to conduct cross-race comparisons of inflammatory factors. However, AfricanAmericans will be reluctant to partake in conventional antibody testing programs due to medical mistrust andexperiences with racism that are salient in the COVID-19 era. There is thus an urgent need to develop anddeploy culturally-relevant communication and antibody testing programs. Our long-term goal is to identify andreduce unjust COVID-19 racial disparities. The immediate objective is to better encourage understanding anduptake of SARS-CoV-2 antibody testing. The central hypothesis is that African-Americans will be receptive toantibody testing when benefits and limitations are communicated in a culturally effective manner, and whennon-invasive salivary collection methods and assays are used. Our rationale is that combining culturallyeffective health communication with salivary testing will reduce mistrust and promote uptake that can lead tobetter grasping the role of inflammation in COVID-19 disparities. Our aims are to 1) develop and compareeffects of a general versus culturally-targeted video about antibody testing on African American and White Flintresidents' antibody testing attitudes and uptake; 2) identify and compare effects of a general versus culturally-targeted video on activation of medical mistrust and racism-related cognition among African Americans whenconsidering antibody testing; 3) measure and identify multi-analyte inflammatory biomarker profiles among FlintRegistry enrollees who complete salivary antibody testing and compare inflammatory biomarker profiles byrace and antibody status. In collaboration with clinical and community partners, we will prepare and evaluategeneral and culturally-targeted video tutorials about SARS-CoV-2 antibody testing. These brief videos will bedistributed to the Flint community through the Flint Registry - a highly visible local health resource exchange.In collaboration with leading salivary bioscience experts, we will furnish an opportunity to engage in at-homesalivary antibody screening - a non-invasive route to antibody testing that is highly suited to disparities-oriented COVID-19 research. The proposed research is innovative and significant in highlighting that culturally-targeted communication and non-invasive antibody testing are vital to propelling disparities-orientedinflammatory COVID-19 research. Knowledge to be gained includes video tutorials and insights aboutcommunity-facing salivary collection that can be immediately disseminated across SeroNet to better promoteincluding racial monitories in ongoing studies of inflammation and antibody testing.",2020,2022,Michigan State University,1326405,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Prognostic factors for disease severity | Approaches to public health interventions | Community engagement | Communication,2020 +C07190,3U54MD010724-05S1,Monitoring COVID19 and Building Capacity with Northern Plains Tribes and the Future of Pandemics,"Monitoring COVID-19 and Building Capacity with Northern Plains Tribes & the Future of PandemicsAbstract: The spread of COVID-19 across the world and throughout the United States has brought extant disparities inhealth care resources and capacity into new focus as the various health, economic, and social harms of COVID-19 disproportionately fall upon under-invested communities. Ongoing limitations in testing capacity, medicalinfrastructure and resources, and strong community partnerships are leading to greater spread of COVID-19,more difficulty in balancing precautionary isolation vs economic decisions, and a lack of data to guide publichealth policies. At the same time, efforts to overcome these issues that are led by faraway groups without localknowledge or consent can not only result in the promotion of ineffective solutions over local needs, but can alsoperpetuate ongoing harms to health, social, and economic concerns. Therefore, solutions that aim to addressCOVID-19 public health capacity in under-resourced environments must include local resources, local consent,and ensure long-term capacity, shared equity, and data control for participants. Here, we propose to leveragepre-existing resources and partnerships between the Stanford School of Medicine & tribal affiliates to upgradeexisting laboratory infrastructure for conducting COVID-19 diagnostic tests, health consultations, and tribe-widepublic health data management and policy. This capitalizes on existing resources built with the Native BioDataConsortium (NBDC)-an Indigenous-led research group- from its collaboration with the SPHERE Project 1 Bio-Repository for American Indian Capacity, Education, Law, Economics, and Technology (BRAICELET) center.The work proposed here was designed to result in a tribe-governed health resource being operational within 6months to conduct COVID-19 diagnostic tests and monitoring on an ongoing basis for improved public health.",2020,2022,Stanford University,3305591,Human Populations,Other,Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Diagnostics | Disease surveillance & mapping | Community engagement,2020 +C07191,3U54MD002316-14S1,Leveraging Bio-Cultural Mechanisms to Maximize the Impact of Multi-Level Preventable Disease Interventions with Southwest Populations,"Title: Eliminating COVID-19 disparities in Arizona in partnership with underserved/vulnerablecommunitiesAbstract Arizona has one of the highest COVID-19 positivity test rates (approximately 19%) in the U.S. Positivityrates are disproportionally higher among Arizona's Latinx, American Indian and African American communities.The proposed community driven and culturally congruent intervention aims to increase access to testing byidentifying and decreasing barriers to testing in vulnerable and underserved communities across Arizona. Theintervention aims at reducing disparities in COVID-19 diagnostics, education, wraparound services andreferrals to a primary care provider, with the ultimate goal of improving the health of underserved communities.The proposed approach empowers local communities, meets community members where they are, is datadriven, and creates the infrastructure for continued community-driven delivery of care. Following a Community Based Participatory Research (CBPR) orientation, the project will: (a) identifyand prioritize testing deserts, (b) coordinate testing at different levels of the social ecosystem, (c) engage andtrain local Community Health Workers (CHWs) deliver saliva-based COVID-19 testing to vulnerable andunderserved community members, (d) deliver test results within 72 hours, (e) provide wrap-around servicesand provider referrals for those testing positive, and (f) sustain the intervention during a follow-up period. Equality Health Foundation serves as the lead community partner and convener of a growing COVID-19 Coalition of Communities of Color Partners (CCCCP) from across Arizona. The ASU Biodesign ClinicalTesting Laboratory (ABCTL) will provide the saliva-based SARS-CoV-2 molecular diagnostic. The saliva test'smain benefits are: a) minimal to no PPE requirements compared to nasopharyngeal (NP) swabs; b)convenience and economy of specimen collection; c) ease of repeat sampling; d) administration by minimallytrained CHWs and e) greater sensitivity and consistency of saliva tests than NP swabs. The project aims toadminister 29,000 saliva tests, 10,000-12,000 at identified testing deserts during the launching period, doublingthe numbers during the follow-up period in Year 1, and adding 5,000 tests in Year 2. A longitudinal evaluationwill assess the intervention's impact by comparing randomly selected participants in the R.A.P.I.D. interventionduring the launching period (N=500) with a matched comparison group (N=500) randomly selected fromstandard testing sites. ASU's existing NIMHD-funded U54 Specialized Center of Excellence (RFA-MD-17-005;5U54MD002316-14) with its Community Advisory Board and in collaboration with key government, communityorganizations, tribal governments and academic partners is well equipped and eligible to undertake theproposed revision. The aims of this emergency competitive revision match and enhance the aims of the currentU54 award and the assembled transdisciplinary team has the infrastructure, capacity, and communitypartnerships in place to implement the project.",2020,2022,Arizona State University-Tempe Campus,3444552,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience",Diagnostics | Approaches to public health interventions | Community engagement,2020 +C07192,3U54AG063546-02S2,Improved Testing for COVID-19 in Skilled Nursing Facilities: IMPACT-C,"The COVID-19 pandemic has disproportionately affected skilled nursing facilities' (SNF) residents and workers,and it is the biggest challenge U.S. SNFs have faced in decades. SNF healthcare workers are also oftendisadvantaged persons at risk for contracting the virus. Thus, universal testing of residents and workers hasbeen a key management approach to containing viral spread. COVID-19 has magnified long-standing healthdisparities in the quality and outcomes of care among minority SNF residents. Equitable SARS-CoV-2 testingstrategies have a critical role to play in mitigating such disparities. This proposal's overarching goal is toleverage the foundation of the NIA IMbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory toestablish IMPACT-COVID-19 (IMPACT-C) which will be dedicated to developing and evaluating SARS-CoV-2testing strategies among highly vulnerable SNF residents and workers. The Aims are to: 1) Establish theinfrastructure of IMPACT-C; 2) Describe disparities in SARS-CoV-2 testing, and identify resident, facility andpolicy characteristics associated with COVID-19 outbreaks and outcomes; 3) Engage key stakeholders todevelop culturally sensitive SARS-CoV-2 testing strategies; and 4) Design and conduct cluster RCTs of SARS-CoV-2 testing strategies embedded in SNF heath systems. All data will be shared with the RADx-UPCoordination and Data Collection Center. The organizational, administrative, and expertise components forIMPACT-C will include: leadership, regulatory structures, dissemination, and investigators. IMPACT-C will alsoleverage IMPACT's Data Sharing Collaborative that includes 11 national companies that collectively own over1,000 SNFs and use a common electronic medical record (EMR) platform. We have already established theinfrastructure to securely and regularly receive daily EMR and COVID-19 data from this consortium and link itto Medicare claims and Minimum Data Set assessments. Using this rich and representative database, we willconduct a series of models to inform policies on SARS-CoV-2 testing and to forecast outbreaks. Further, wewill leverage IMPACT's resources to develop a diverse and engaged group of stakeholders who will identifybarriers to SARS-CoV-2 testing in SNFs, develop solutions, and inform the development of future testingstrategies to be tested in a cluster RCT (Aim 4). We have designed a cluster RCT of 120-150 facilities tocompare the effect of novel, point-of-care testing versus usual care on the rate of COVID-19 infections. TheCOVID-19 pandemic is rapidly evolving, and we have the expertise to modify the proposed trial based onadvances in testing technology, improved access to point-of-care testing in SNFs, stakeholderrecommendations, and regional policies. Ultimately, IMPACT-C will be well-poised to rapidly and rigorouslyconduct a vaccine trial. In summary, IMPACT-C will establish the infrastructure and expertise to develop andevaluate SARS-CoV-2 testing strategies for SNFs that are compassionate and culturally sensitive, but at thesame time, are nimble enough to respond to rapid advances in testing modalities and vaccine development.",2020,2022,Brown University,3572603,Human Populations,Unspecified,Unspecified,Unspecified,Other,Hospital personnel,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Immunity | Disease susceptibility | Disease surveillance & mapping | Approaches to public health interventions,2020 +C07193,3P30DK111024-05S1,Rapid Optimization of COVID-19 Testing for People Affected by Diabetes,"PROJECT SUMMARY/Abstract: The Georgia Center for Diabetes Translation Research (P30DK111024) proposes to leverage its interdisciplinaryexpertise (clinicians, implementation and behavioral scientists, public health, technology, and diabetes experts)and collaborations (community, academic, government, and health system partners) to rapidly scale a COVID-19testing program for adults and children who are at high risk due to background metabolic disease (i.e., diabetes,obesity, or elevated risk of diabetes). The ""Rapid Optimization of COVID-19 Testing for People Affected byDiabetes"" program will adapt, optimize, and iteratively evaluate and refine a testing and education strategydelivered through our network of Federally-Qualified Health Center (FQHC) partners. We focus on Georgia, anational epicenter of diabetes, which is experiencing rapidly escalating COVID-19 cases, morbidity, and mortality.Yet, the state has not accelerated testing opportunities, leaving critically underserved subgroups at high-riskwithout access to testing. Building on technologies and innovations designed by this team, we will addressaccess gaps, optimize resource allocation to meet high risk groups where it suits them best, and support peopleat the time of and after their test results. Guided by the EPIS framework, our implementation program will learnhow to scale the strategy, combining approaches to reach high-risk groups through testing enhancement atFQHC partner sites and other community testing centers with a ""test your bubble"" approach to provideopportunities for all household members to get tested. To achieve this, we will conduct geospatial analyses toidentify localities of ""testing deserts"" within counties with high densities of people at risk for COVID-19 infection,hospitalization, and mortality (Aim 1; Exploration); engage community and clinic stakeholders to formativelyunderstand what barriers and facilitators influence testing and what strategies are well-received by users (Aim 2;Preparation); develop models that provide real-time guidance on whom to test, where to test, and when to test(Aim 3; Preparation); and deploy and evaluate the program at testing site partners using rapid-cycle testing in apre-post effectiveness-implementation type 2 hybrid study (Aim 4; Implementation). Sustainability will bemeasured through continuous quality improvement efforts (Aims 2, 4) and future research. Data from this studywill motivate further programs and studies of how to scale serological testing and vaccination (in the future) andhas huge relevance for underserved areas of other states. We will evaluate this program in terms of its reach,effectiveness, adoption, implementation, and maintenance (REAIM). We have extensive experience applyingthese transformative innovations to reach populations. We will leverage partnerships with the GeorgiaDepartment of Public Health, nationally-recognized expertise via the NIH-funded Rapid Acceleration ofDiagnostics Validation Core at Emory University, National COVID-19 Resiliency Network at Morehouse's Schoolof Medicine, and the Georgia Clinical and Translation Science Alliance's Community Engagement Program.",2020,2022,Emory University,3786234,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease surveillance & mapping | Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication",2020 +C07194,3U54MD010711-05S1,Community-Engaged Research on COVID-19 Testing in the US Territories,"Abstract: COVID-19 has created an unparalleled health crisis across the globe that has ravaged underserved and vulnerablepopulations in the US, including in the territories of Puerto Rico (PR) and the U.S. Virgin Islands (USVI). Whiletesting for COVID-19 has increased in the Caribbean territories, it is still deeply inadequate. The USVI and PR haveexperienced barriers to wide-spread testing, including an overall shortage of testing equipment and supplies, whichhas led to a sharp increase in cases since early July. Data from our Eastern Caribbean Health Outcomes ResearchNetwork Cohort Study (ECS) indicate nearly 61% of our population-based random sample (n=3000) has at leastone chronic condition, making them high risk for severe complications from COVID-19. We propose to enhance andamplify the COVID-19 diagnostic testing cascade in the USVI and PR by utilizing community-based assets-Federally Qualified Health Centers (FQHCs) and their community organization (CBO) partners-to address barriersto full participation in the testing continuum from diagnosis through to self-isolation and quarantine. We will partnerwith 3 FQHCs-one in PR and two in USVI-and CBO partners for each. We will provide FQHCs with protocols fordiagnosis and follow-up and will procure new testing technologies to make testing more efficient. CBOs connectedto the FQHCs will help reach underserved community members not currently being tested, such as those withelevated medical risk, those living without homes, or those living in congregate settings such as nursing homes.After notification of a positive result, we will support FQHCs to provide ambulatory care for active clinical monitoringat home and will deploy a screener for social determinants of health. CBO partners will connect patients with socialneeds to resources to support quarantine and self-isolation recommendations. We will additionally assess thediffusion and uptake of FDA authorized and approved testing technologies across existing and emerging testingmodels. We will utilize a rigorous quasi-experimental approach to focus on assessing our implementationoutcomes. Specifically, we will employ a hybrid III implementation-effectiveness study design. The primaryimplementation outcome will be reach-a measure of the amount of testing that is being done in the community-using an interrupted time series design (ITS). Other outcomes of interest include adoption of new testingtechnologies, fidelity to the intervention, its acceptability, and its effectiveness. We will deploy the RE-AIMframework to guide the evaluation of the intervention. Throughout the project period, we will collaborate with theRADx-Up Coordination and Data Collection Center (CDCC) across all activities, including harmonizing datacollection and procuring new COVID-19 testing technologies. We will also work closely with the CommunityEngagement domain to enhance the experience of our participating stakeholder partners. Finally, the enhanceddiagnostic testing cascade will improve reach, access, uptake, and effectiveness for underserved and vulnerablecommunities in the USVI and PR. This will strengthen the capacity of each stakeholder organization to contribute tovaccine distribution networks for influenza now and a SARS-CoV-2 vaccine in the future.",2020,2022,Yale University,3740347,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C07195,3U54GM115677-05S1,Rhode Island Center for Clinical and Translational Science,"SUMMARY Nationally, Latinx individuals have four times the rate of SARS-CoV-2 diagnoses compared to Non-Hispanic Whites. Furthermore, Latinx populations may face barriers in accessing SARS-CoV-2 tests, receivingtest results, interpreting test results, and getting appropriate follow-up care. Improved understanding of thesources of health equity differences for Latinx populations can be used to better guide allocation of resourcesand provide essential data for provider organizations seeking to support those in the most need. This RADx-UP project will establish a statewide research and monitoring infrastructure in partnership with communityclinics. We will develop community health teams (""Promotoras Teams"") with the largest Latinx communityorganization in Rhode Island to address identified barriers to COVID-19 testing through patient navigation,health literacy support, and follow-up care. The overall goals of the proposed study are to improve testing uptake and the understanding of SARS-CoV-2 outcomes among Latinx populations. We will build on partnerships with community clinics that serve ahigh proportion of Latinx individuals (>50%) in Rhode Island. We will place particular emphasis on disparities incare faced by Latinx populations and factors that have been identified as impacting health equity in RhodeIsland (integrated healthcare, community resilience, physical environment, socioeconomics, and communitytrauma). The insights gained from the quantitative and qualitative approaches will be used to guide theimplementation of community campaigns to improve testing among Latinx populations that are in identifiedlocations with lower per capita testing than other parts of the state (""testing deserts""). This RADx-UP project will utilize a unique approach and infrastructure to monitor SARS-CoV-2 testingrates, including the use of the statewide Health Information Exchange (HIE) in Rhode Island that connects dataacross primary care, urgent care, specialty care, and acute care clinical environments. The HIE containsclinical data for most people receiving care in Rhode Island including SARS-CoV-2 test results from majorlaboratories and other facilities (e.g., CVS MinuteClinic). These quantitative data will be combined withqualitative data and organized according to the Consolidated Framework for Implementation Researchframework to guide our mixed-methods explanatory sequential design. The specific aims of this project are to:(1) Identify COVID-19 hotspots and testing deserts using a near-real time geographic information systemmonitoring system; (2) Determine community and provider barriers that impact access to SARS-CoV-2 testing;and, (3) Implement community-based approaches to improve SARS-CoV-2 testing. This RADx-UP project willdevelop a community-based infrastructure to enable structured, longitudinal relationships with a historUicallyunderserved patient population. Such insights will provide essential data for a population level decision supportsystem guiding testing prioritization and for future consideration of vaccine-based prevention strategies.",2020,2021,Brown University,899640,Human Populations,Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Disease surveillance & mapping | Supportive care, processes of care and management | Approaches to public health interventions | Policy research and interventions | Social impacts | Economic impacts | Other secondary impacts",2020 +C07196,1U54CA260581-01,Tulane University COVID Antibody and Immunity Network (TUCAIN),"Overall Summary: The SARS-CoV-2 virus, the causative agent of COVID-19, has infected a reported 13,810,247 persons globallyas of July 16, 2020 with a mortality rate of 4.2%. In the State of Louisiana, over 7.3% of the 86,411 COVID-19cases involve people living with cancer. Theoretically, convalescent plasma contains protective antibodies thatneutralizes virus and mitigates its pathogenic effects. Yet, there remains a large gap in our understanding of themechanisms that drive humoral and cellular immune responses and how these responses correlate with diseasecourse and protection as well as the durability of those responses. Furthermore, there is a need for serologicalassays that measure these responses accurately for serodiagnosis and as correlates of immunity and protection.Without this knowledge, the true efficacy of convalescent plasma as therapy for COVID-19 and ourunderstanding of the humoral immune response to SARS-CoV-2, especially in immunocompromised patients,will remain unknown.The overall goal of the Tulane University Convalescent Antibody and Immunity Network (TUCAIN) is tocharacterize this response with respect to functionality and durability. We will achieve this goal by investigatingthe following broad specific aims: (1) Characterize the evolution, function and longevity of the humoral immuneresponse to COVID-19. (2) Identify cell mediated immune responses that contribute to durable or short-livedhumoral immunity to SARS CoV-2. (3) Correlate protective and potentially pathogenic immune responses to theclinical course of hospitalized COVID-19 patients. We will achieve these goals by studying a diverse cohort ofCOVID-19 survivors and minimally sick seroconverters, including a large cohort of patients with malignancies.Using serial blood collections, we will apply several immunological technologies to study the evolution anddurability of the immune response over time. We will also correlate these responses to patient outcomes anddisease pathogenesis using a ""big data"", systems biology approach. An approach, such as the one we propose,will allow us to determine if COVID-19 survivors develop long-term, antibody-based protection and we canconfirm if convalescent plasma has therapeutic potential. This research will allow us to identify new targets formedicines and vaccines, inform personalized treatment strategies such as those required byimmunocompromised patients with cancer, and to provide novel immunological algorithms applicable to a widerange of human pathogens.",2020,2022,Tulane University Of Louisiana,3743182,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C07197,1U54CA260563-01,Immune Regulation of COVID-19 Infection in Cancer and Autoimmunity,"Abstract:The Emory U54 SeroNET U54 program is a multidisciplinary program that brings togetherexperienced team of investigators to tackle fundamental issues relating to immunity toSARS CoV-2, particular in patients with cancer and autoimmunity. The team has a longtrack record of prior work in basic and translational studies in the setting of viral infections,vaccines and cancer. The program consists of 3 interacting projects and two essentialcores in addition to the administrative core. Studies in project 1 (led by Sanz) will studythe biology of SARS CoV-2 specific effector B cell responses in patients withautoimmunity, with a particular focus on extrafollicular B cell pathway. Studies in project2 (led by Sekaly and Wrammert) will study the role of inflammatory milieu in regulatingantiviral immunity and in the development of long term memory responses. Studies inproject 3 (led by Dhodapkar and Ahmed) will focus on studying the impact of specificcancer therapies, in particular B/plasma cell depleting therapies in patients with B/plasmacell malignancies, and immune checkpoint blockade in patients with lung cancer. Thesestudies will also set the stage for studying immune responses to future SARS CoV-2vaccines in patients with autoimmunity as well as cancer patients. The programs aresupported by active cores (led by Roback and Neish) which have experience withmonitoring immunity to SARS CoV-2. Together, this program will not only provide basicinsights into immune-pathogenesis of COVID, but also provide the consortium withaccess to unique patient populations at higher risk of COVID-related mortality.",2020,2022,Emory University,3963391,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C07198,3R01DA036832-07S1,Preventing Substance Use in the Context of Poverty: Risk and Protection from Early Childhood to Early Adulthood,"Abstract: The COVID-19 pandemic has impacted the lives and well-being of people across the world. In the UnitedStates, different states have adopted different measures to limit the spread of COVID-19, but the impact of aslowed economy, increased social isolation, and the loss of typically-available support services hasdisproportionally affected racial and ethnic minorities, as well as those in disadvantaged socioeconomicgroups. Tobacco, marijuana, alcohol, opioid, and illicit drug users are likely vulnerable to COVID-19 because ofthe effects of those substances on the respiratory and immune systems, and people who are in treatment orrecovery from substance misuse may be at risk for relapse because of increased mental health issues andadditional barriers to obtaining treatment and support. There are indications that substance use has increasedbecause of the pandemic, but rigorous prospective studies have yet to be conducted. The Early Steps MultisiteStudy of diverse lower income families, recruited from three geographic areas across the country(Pennsylvania, Virginia, and Oregon), presents unique research opportunities during this pandemic. There is awealth of data available on the Early Steps participants, including the history of substance use, social andhealth service utilization, and mental health of both primary caregiving adults (current Mage = 43.8; SD = 7.4)and youth (current Mage = 18.6; SD = 0.5). As the study design also included a randomized control trial of theFamily Check-Up intervention, we can also test the potential protective effects of the intervention on COVID-19related outcomes. We plan to administer two COVID-19 related surveys to Early Steps participants, at both 6months post-COVID-19 (September of 2020) and at 12 months post-COVID-19 (March of 2021). Our first aimis to examine the effects of the COVID-19 pandemic on substance use, mental health, and service utilization(i.e., addiction treatment, access to health care) in both caregiving adults and their young adult children. Weplan to test the extent to which a history of mental health problems among parents and young adultsmoderates the effects of COVID-19 on their substance use, and to test the extent to which service utilization atthe 6-month assessment mediates the effects of COVID-19 on substance use at the 12-month assessment inadult caregivers and young adult children. We will examine differences by geographic location, race/ethnicity,biological sex, and income. We hypothesize that those with more service utilization at 6 months post-COVID-19 will have less substance use at 12 months post-COVID-19. Our second aim is to examine the potentialbuffering effects of the Family Check-Up on substance use and mental health outcomes 6 and 12 monthsfollowing the onset of COVID-19, with those families randomly assigned to the intervention expected to showlower levels of substance use, mental health problems, and greater service utilization. We also will examinemoderators of potential FCU protective effects, including child, family, and community risk factors. These datacan begin to illuminate the wide-ranging impact of COVID-19 on vulnerable populations.",2020,2021,University Of Pittsburgh At Pittsburgh,150591,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Drug users | Sex workers,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Post acute and long term health consequences | Clinical trials for disease management | Policy research and interventions | Indirect health impacts | Social impacts | Health service delivery,2019 +C07199,3U01EB029242-02S1,Using the GoFlowChip to understand SARS-CoV-2 infection of the gastrointestinal mucosa of humans and bats,"Summary The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectioushuman respiratory tract pathogen that has the capacity to infect many different organ systems, including thegastrointestinal (GI) tract. The overall goal of this project is to elucidate the role of the GI mucosa in SARS-CoV-2 infection and transmission. Specifically, we seek to identify mucosal immune mechanisms involved inCOVID-19 pathogenesis and compare epithelial responses to SARS-CoV-2 in the gut of humans and bats.Investigating bat cells is important, because bats are considered the original hosts for SARS-CoV-2, but do notdevelop overt disease upon infection. Our recently developed GOFlowChip platform, which integrates 3-dimensional GI organoids and immune cells on a millifluidic chip with luminal and basolateral flow capacity, isideally suited to probe the mechanisms involved in SARS-CoV-2 infection of the gut mucosa. Here, wepropose to utilize the GOFlowChip to elucidate mechanisms of viral infection, replication and spread involvedin SARS-CoV-2 infection of the GI tract. Specifically, we seek to (1) Define how SARS-CoV-2 infection of theGI epithelium contributes to viral spread. (2) Determine to what extent GI mucosal immune mechanismsregulate SARS-CoV-2 infection and spreading in the GI tract. (3) Compare GI epithelial responses to SARS-CoV-2 between bats and humans. For Specific Aim 1, we will optimize the GOFlowChip for use under BSL-3laboratory conditions, followed by SARS-CoV-2 infection experiments that will elucidate susceptibility and viralreplication dynamics in different gut compartments. Specific Aim 2 will leverage our organoid-mononuclearphagocyte (MNP) co-culture system to elucidate whether MNP-dependent transport mechanisms impact viralinvasion of the GI mucosa, and we will screen SARS-CoV-2 reactive patient sera for their ability to modulategut infection. For Specific Aim 3, we will establish organoid lines from bat GI tissues in order to compareepithelial responses to SARS-CoV-2 in bats and humans using RNA sequencing in order to understanddifferences in viral pathogenicity between humans and bats. The proposed work is directly integrated with ourexisting project, because we will use out GOFlowChip to investigate how SARS-CoV-2 interacts with epithelialcells and immune system components to cross the GI barrier. Our research is technologically innovative,because we are using gut organoid-immune cell co-cultures in a fully contained tissue chip design to study aBSL-3 level pathogen. Our project is conceptually innovative, because it is the first to compare gut organoidsfrom Jamaican fruit bats to human organoids for their ability to sustain SARS-CoV-2 infection and to mountcellular antiviral responses. The proposed research is significant because it will yield crucial information on therole of the GI mucosa in COVID-19 pathogenesis that may inform future strategies to identify viral carriers,prevent viral transmission, and design novel antiviral treatments and vaccines.",2020,2022,Montana State University - Bozeman,493788,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis",2020 +C07200,3U01DA040381-05S1,Community-Engaged Research on COVID-19 Testing Among Underserved and/or Vulnerable Populations,"Project Summary/Abstract: The SARS-CoV-2, also known as COVID-19 pandemic has caused disastrous and unprecedented publichealth and economic consequences in the U.S., seriously affecting Americans' physical and mental health.Death rates attributable to COVID-19 among minority populations are several folds higher than amongpredominantly White counties. South Florida and specifically Miami-Dade County is an epicenter of the COVID-19 pandemic, where non-Hispanic Blacks and Latinos are overrepresented in COVID-19 related hospitalizations and deaths. Pervasive structural inequities and social determinants of health are the maincause of health disparities due to a complex interaction of multiple factors including individual and societal riskfactors. Understanding the impacts of these factors on health and social consequences of the pandemic hasbroad policy implications, especially for the acceptance of testing and future vaccines. The proposed researchwill address the impact of COVID-19 on vulnerable minority populations and examine (1) the barriers to testing and uptake of future vaccines, (2) effectiveness of community engagement to increase the uptake of COVID-19 testing in the underserved communities, (2) acceptability, sensitivity and specificity of using less invasive testing methods compared to nasopharyngeal swabs, and (3) assessment of barriers and potential strategies to engage community members and community organizations in COVID-19 testing and vaccine deployment. We propose to conduct community-engaged research studies in collaboration with community-based partners to (a) determine barriers to testing, and uptake of future vaccines, including health literacy,stigma, drug use and financial burden associated with testing, follow-up care, feasibility of effective self-isolation if positive, and perceived effectiveness of testing and vaccination, (b) assessment of the acceptabilityof extensive community outreach and deployment of a mobile COVID-19 testing unit to geographical areas occupied by underserved and vulnerable populations in close proximity to our community partner, BorinquenHealth Care Center (BHCC), and (c) compare the acceptability, sensitivity, and specificity of alternative approaches to obtain samples, including medically administered nasopharyngeal swabs, saliva, and self-swabbing options sampled simultaneously. The goal is to improve understanding of COVID-19-related healthdisparities, enhance access, effectiveness, and implementation of COVID-19 testing in vulnerable and/orunderserved populations and to mobilize the community to develop culturally-appropriate strategies to mitigatethe COVID-19 epidemic and increase acceptance of future vaccines. The potential for evidence-basedapproaches to address COVID-19 disparities will be facilitated by our community-based partners that have theresources to provide community engagement, follow-up care, and public health mitigation for cases who testpositive; the PI who manages a CLIA-certified laboratory at the university and a research team experienced inrecruiting and retaining >1,000 study participants from the same vulnerable and underserved populations.",2020,2022,Florida International University,3032553,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy",2020 +C07201,1U54CA260517-01,Mechanisms and Duration of Immunity to SARS-CoV-2,"OVERALL: Summary: We propose the Stanford U54 SARS-CoV-2 Serological Sciences Center of Excellence (SUSS-COE) as amember of the SeroNet consortium gathered to address the urgent need for better understanding of human immune responses to the SARS-CoV-2 coronavirus pandemic that has engulfed the U.S. and the world.Our Center will be based on four scientific pillars:  Deep mechanistic analysis of the adaptive immune responses of COVID-19 patients, spanning serological, B cell and T cell responses,  Analysis of immune responses in the blood as well as mucosal sites,  Comparing immune responses induced by infection to those induced by candidate vaccines, and  Studying medically underserved, underrepresented and at-risk patient populations Within these parameters, we will attempt to determine the factors that result in effective and durable immunity to SARS-CoV-2 infection.We are dedicated to broad collaboration, rapid sharing of data and technical knowledge, nimbleness in responding to the rapidly changing pandemic, and rapid translation of research findings to CLIA Lab clinical testing and development of new therapeutic approaches. We feel these are the best routes forward for addressing gaps in our understanding of the determinants of protective immunity to SARS-CoV-2, and providing useful tools for physicians and patients.",2020,2022,Stanford University,4017422,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07202,3P30AI094189-09S1,The Johns Hopkins Center for AIDS Research (JHU CFAR) RADx-UP,"Project Summary: The novel Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (SARS-CoV-2or COVID-19) pandemic has exacted a grievous toll on human existence exacerbating underlying disparities and disproportionately impacting minority, impoverished and elderly populations. Moreover, testing and contact tracing have been identified as critical for reducing community transmission, yet uneven access by race/ethnicity, income and geography limit effectiveness. Proposed is a cluster-randomized trial of testing modalities with longitudinal follow-up in an urban city with COVID-19 disparities illustrative of national trends. We propose the following Specific Aims: 1) To determine multilevel (socioeconomic, behavioral) barriers and facilitators to SARS-CoV-2 testing using a population representative sample of households in Baltimore, MD; 2) To define the optimal SARS-CoV-2 testing modality for maximizing testing acceptance, uptake andtimeliness of providing results through a cluster-randomized comparative effectiveness trial; 3) To evaluate the impact of testing modality and receipt of positive results on subsequent testing behavior and other behavioral,economic and clinical outcomes; and 4) To serve as a platform for future investigations related to SARS-CoV-2 transmission and COVID-19-associated morbidity and mortality. We will recruit a population representative sample of ~1,300 households in Baltimore City. Two-stage sampling will select census block groups (CBGs) and households within CBGs with oversampling to ensure representation of vulnerable groups. Of 105 selected CBGs, 36 clusters will be allocated in a stratified randomization approach to one of three testing modalities including: 1) self-administered home collection (swab/saliva/blood) kit sent to home with returnpackaging; 2) referral to a community-based mobile testing van; or 3) referral to the nearest fixed testing site (as optimized standard of care). All household members will be randomized to the same modality. The primary outcome will be timely completion of testing and receipt of results; secondary outcomes will include the proportion undergoing testing, and time from testing to receipt of results. During six months of follow-up, we will monitor households for new onset COVID-19 symptoms and exposures and if evident, offer re-testing by previously assigned modality. In addition to testing outcomes described in Aim 2, we will examine individual and household-level behavioral (e.g., adherence to self-isolation, social distancing, mask wearing), economic(e.g., unemployment, time to return to work, housing instability), and clinical outcomes (e.g., severity ofinfection, hospitalization, mortality - endpoints which can uniquely be captured systematically through linkagewith a Maryland State health information exchange linkage. High-quality evidence from this comprehensiveeffort will identify multifactorial drivers of testing disparities, provide rigorous data for the most effective testing strategies, and longitudinally monitor behavioral, economic and clinical impact of testing uptake and modality.Ultimately, we will inform national and local large-scale testing programs critical for pandemic control.",2020,2022,Johns Hopkins University,3222658,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Policies for public health, disease control & community resilience","Diagnostics | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication",2020 +C07203,3R01AG060011-03S2,The role of precarious work in the production of health disparities in older ages,"Abstract: The COVID-19 pandemic has highlighted - and exacerbated - the pervasive race/ethnic and social class based health inequities in the US today. Our essential but precarious food provision, service, and delivery workers areat increased risk of exposure to SARS-COV-2 and related health consequences. At present, the robust guidelines prepared by the Occupational Safety and Health Administration are not enforceable and COVID-19 related paid leave provisions are largely inaccessible by this segment of the workforce. Our objective is to show how workplace and other contexts shape individual behavior and define the role of employment quality in the hindrance or expansion of access to resources and opportunities necessary for engagement in individual-level COVID-19 prevention behaviors. Through individual structured and semi-structured interviews with older low wage food provision, service, and delivery workers in the states of Indiana and Washington, we aim toanswer three research questions: 1) What do older workers know about COVID-19 prevention and where do they get their information? 2) What are the personal and social factors that drive adherence or non-adherenceto prevention practices while at work and compliance with the broad preventive guideline of staying homewhen feeling sick? 3) How does place (including local policies, political culture, industry, and demography) influence the adherence to COVID-19 prevention practices for older workers? We will conduct 40 interviews per site (n = 80 total) with low income workers over 50 years old employed in the food provision, service and delivery industries, recruiting participants through social media and other venues. A stratified purposeful sample will allow identification of major variation across subgroups of interest, and facilitates comparisons across the two sites. Subgroups of interest will be defined by high versus low contact with others at work,race/ethnicity, sex/gender and education. In addition we will compile and review documents and prepare descriptive statistics from publicly available sources to understand the influence of place-based factors in hindering or improving adherence to COVID-19 prevention practices. In conducting this qualitative inquiry, we leverage our multidimensional conceptualization of employment quality as a framework for probing and contextualizing the experiences of these precarious essential workers. Knowledge gained through rich qualitative interviews will shed light on workplace interventions and policies that may improve prevention practices and reduce likelihood of infection with the virus while also improving public health messaging for this vulnerable population.",2020,2021,University Of Washington,234766,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,"Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures",2018 +C07204,3P20GM103653-09S1,Social and behavioral implications for COVID-19 testing in Delaware's underrepresented communities,"Summary: Social and behavioral implications for COVID-19 testing in Delaware's underrepresented communities The COVID-19 pandemic has put a spotlight on our nation's stark disparities in health and burden of diseaserelated to race, ethnicity, socioeconomic status, and literacy. Across our nation, the prevalence of the virus is disproportionately high in minority communities as is the number of COVID-19-related deaths. This project will triangulate data from semi-structured surveys, serology testing and census tract-linked public health and economic data to better understand social, behavioral, and ethical factors related to COVID-19 testing in minority communities, and develop communication strategies to increase acceptance of testing and a future vaccine. Social and behavioral factors will be identified through a semi-structured survey, based on the Johns Hopkins University (JHU) COVID-19 Community Response Survey available from the NIH Public Health Emergency and Disaster Research Response (DR2) platform. The survey will collect detailed information on participants' medical history and current health, family structure and living conditions, employment and socioeconomic status, social distancing knowledge and practices,access to health care, presence of symptoms related to COVID-19 in themselves and among their contacts, their history of virus testing, attitudes toward testing, and interest in receiving a vaccine. Working with community partners we will recruit participants from communities which score poorly on Delaware's community health index, and which have also been hardest hit by the virus. The surveys will be combined with rapid, finger-stick serology tests to assess recent (previous 2 - 3 months) infection with the virus. After the initial survey and test we will follow the participants over a 12 month period, repeating the survey and serology test every 4 months. Our longitudinal, cohort design will allow us to track participants' attitudes and adherence to mitigation behaviors, referral of contacts based on their test results,and attitudes toward a future vaccine throughout the changing dynamics of the pandemic and public health response Delaware State University nursing, social work and psychology students will go to trusted sites in thecommunities to administer the serology tests and survey questions to participants. Participants will be given resources for services as appropriate to their test results and health care needs and will also be compensated for their time and information. By following participant's virus-related knowledge, attitudes, testing history and mitigation practices overtime and correlating it with an objective measure of virus exposure, our proposed project will identify strategies to make testing more accessible and acceptable and to increase use and utility of test results among underserved populations.",2020,2022,Delaware State University,576907,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Social Workers | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Impact/ effectiveness of control measures | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Community engagement | Communication",2020 +C07205,3UL1TR002538-03S4,Community-Academic Partnership to Address COVID-19 Among Utah Community Health Centers,"PROJECT SUMMARY/Abstract: Racial/ethnic minority, low socioeconomic status (SES), and rural populations suffer profound health inequities across a wide variety of diseases and conditions, as well as a disproportionate burden of the negative health consequences of the COVID-19 pandemic. Latinos make up ~14% of the Utah population vs. ~40% of Utah's COVID-19 cases, and the case rate is over 3-fold higher in neighborhoods characterized by high vs. low deprivation. The case rate in Utah per 100,000 is 665 among Whites vs. 3,503 among Latinos, 3,470 among Pacific Islanders, 1,727 among African Americans, and 1,569 among Native Americans. Community Health Centers (CHCs) are optimal settings for addressing the screening and uptake of COVID-19 testing among underserved populations. Twelve Utah CHC systems are participating in SCALE-UP Utah. Their 39 primarycare clinics serve over 115,000 unique patients annually (37% Latino, 11% Native American, 61% <100% poverty level, 51% uninsured, and 49% of clinics are in rural/frontier areas). SCALE-UP Utah is a state-wide,pragmatic, multilevel intervention study. The long-term objective is to increase the reach, uptake, and sustainability of COVID-19 screening and testing among underserved populations. The team has existing infrastructure and ""shovel ready"" clinic and population health management (PHM) interventions ready for implementation. SCALE-UP Utah builds on long standing, funded partnerships, and will implement and evaluate three practical, feasible, scalable multi-level interventions to increase COVID-19 screening and uptake in Utah CHCs. Interventions leverage widely adopted Health Information Technology (HIT) at the point of care, text messaging, and patient navigation. SCALE-UP Utah will coordinate and synergize existing infrastructure and resources across the state, as well as strengthen infrastructure and data networks for rapid deployment of new screening and testing protocols, vaccination programs, etc. The project will employ a rapid cycle research approach in which interventions are tested on a small scale, using short time frames (e.g., <1month) and cyclical evaluation cycles. A critical aspect of these rapid-research cycles is that change can be quickly tested on a small scale, and then disseminated to other clinics/patients. The interventions will be readily available for adoption by other low-resource healthcare settings; and, the data will advance population health and implementation science. The specific aims are to: 1. Implement and evaluate clinic and PHM interventions for increasing the uptake of COVID-19 testing among CHC patients across Utah. 2. Examine implementation effectiveness outcomes, as well as characteristics of both clinics and patients that may influence intervention effects and implementation outcomes.",2020,2023,University Of Utah,3762086,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Policy research and interventions",2020 +C07206,3UL1TR002494-03S5,University of Minnesota Clinical and Translational Science Institute (UMN CTSI),"The National COVID Cohort Collaborative (N3C) is a project that is funded by NCATS to build a central registry of patients who have been tested for COVID-19 or have a clinical diagnosis of COVID-19. The Observational Medical Outcomes Partnership (OMOP) data model is the representational format used in the full N3C repository. This project proposes to develop a COVID-19 data extract from the University of Minnesota COVID-19 Registry by mapping it to the OMOP data model in order to support optimal participation in the N3C. The OMOP format will allow us to contribute all of our COVID-19 patient data at a level of detail necessary to study this disease. The University of Minnesota has developed and maintains a CDR that contains the EHR records and ancillary data for 3M patients from affiliated clinics and hospitals of the M Health FairviewSystem. The CDR was created in 2012 and uses a proprietary data model developed at theUniversity of Minnesota which has served our researchers well. In 2017, Fairview HealthSystems merged with another healthcare organization, HealthEast. As of 2020, the HealthEastEHR has not been integrated into the overall Fairview Epic system and no HealthEast EHRrecords are available in the CDR. In March 2020, one of the HealthEast hospitals, Bethesda, was designated as the COVID hospital to treat COVID-19 ICU patients for the combined health system. Because of this, only 50% of our COVID-19 patients' data is available in the CDR.In order to serve the immediate needs of our COVID-19 researchers, a process for extracting COVID-19 related data from the HealthEast system into a University of Minnesota COVID-19 Registry has been implemented. The University of Minnesota has signed the N3C data transfer agreement and will begin participation by extracting data from our ACT i2b2 instance to the N3C. However, none of the HealthEast data is incorporated into our ACT i2b2 database. For complete participation, we propose to map the University of Minnesota COVID-19 Registry to OMOP in order to support optimal participation in the N3C. The OMOP data model provides the optimal mapping with the most detail and gives the N3C the most benefits from our data. This approach will also allow all of the HealthEast COVID-19 patient data to be included in a complete extract of all COVID-19 patients across our entire health system to the N3C with data represented at a level of detail necessary to study this disease.",2020,2023,University Of Minnesota,99921,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2018 +C07207,3U01HG008685-05S2,eMERGE Phase IV Clinical Center at Partners HealthCare,"The Coronavirus Disease 2019 (COVID-19) pandemic has caught the world off guard, reshaping ways of life,the economy, and healthcare delivery. Data in electronic health records (EHRs) should be widely available to study COVID-19 but have not yet been effectively shared across clinical sites, with public health agencies, or with policy makers. There are several large, national and international projects to build informatics infrastructureto analyze the EHR data of patients with COVID-19. However, aggregating data from multiple EHRs only works if you can trust the final results. This means being able to go back to each site and talk to the people who know the data best, to understand the local clinical guidelines, coding practices, data quality problems, and other factors that affect the data. In March, 2020, we launched an international effort called the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). It brings together more than 100 informatics experts, statisticians,and ICU doctors from around the world. The novel aspect of 4CE is that we recognize the complexities of EHR data and the need to directly involve the local data experts, not only in the data collection, but also in the development of research questions and the data analyses. We try to move fast, believing that early intelligenceis worth more than complete intelligence later. To do this, we avoid roadblocks that typically slow down informatics projects, such as building or installing new software, or the regulatory hurdles involved in sharing patient-level data. Instead, we ask participating sites to run analyses locally, using simple existing tools, likeSQL, R, and Python scripts, and only share aggregate counts and statistics centrally with the rest of the 4CEconsortium. We review and validate the data as a group, identify and fix data quality problems, and ask sites to repeat the analyses until everything is right. Through multiple cycles of data verification, we iteratively clean up the data and gain confidence that the findings we are seeing are real. Because we can do this quickly, we go from research question to results in just a few weeks. This proposed project will ""productize"" the 4CE approach, through three Specific Aims: (1) Transition 4CE to ""Phase 2"", where sites will begin more complex local analyses.We will develop Phase 2 analysis scripts; update our data upload, validation, and visualization websites; and,test the Phase 2 scripts at three sites before expanding to the rest of the consortium. (2) Demonstrate and evaluate 4CE through two use cases. We will refine and validate an algorithm for identifying COVID-19 patients with ""severe"" disease and use 4CE to characterize central nervous system complications in COVID-19. (3) Develop a plan for integrating with complementary efforts and long-term sustainability. As part of this, we willcreate a guide that shows sites how to use 4CE data extracts and quality checks to support other COVID-19 informatics projects, including the generation of OMOP files.",2020,2025,Brigham And Women'S Hospital,883131,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C07208,3S06GM127983-03S1,RAD-X UP NARCH Supplement: A Cherokee Nation Community-Driven Program for Testing and Contact Tracing (Cherokee PROTECT),"PROJECT Summary: Through the RADx-UP program, the Cherokee Nation Community-Driven Program for Testing and Contact Tracing (Cherokee PROTECT) unites tribal, academic, and community partners under the leadership of Cherokee Nation (CN) to solve a dire need for COVID-19 testing, contact tracing, and culturally informed education in underserved and vulnerable rural populations. As of August 4, Cherokee Nation Health Services (CNHS) has confirmed >850 cases of COVID-19 in the tribal populations served across mainly rural northeastern Oklahoma. Community spread of COVID-19 exists throughout all 14 counties in the CN reservation, but with CN's limited capacity for community testing, screening, and contact tracing, the true impact of COVID-19 is unknown. Roughly 34% of American Indian/Alaska Native (AI/AN) adults aged 18-64 years are at risk of severe COVID-19 due to comorbidities, more than any other racial/ethnic group in the US.Five counties in CN are in the top 20% of US counties for the prevalence of adults at risk of severe COVID-19due to underlying medical conditions; this vulnerability is compounded by high poverty rates and geographic barriers. People living in rural areas of CN may have to travel as many as 60 miles round-trip for viral testing.Most COVID-19 testing in CN to date has been conducted through CNHS, the largest tribally compacted health system in the US that serves all AI/AN people living within the CN reservation. Although CNHS accounts for approximately 8.5% of all IHS active user population and 38% of active user population of Oklahoma service area, not all tribal members residing in the reservation access CNHS, and therefore, may not be tested by CNHS. Other than CNHS clinics, 7 of 14 counties in this area have only one public testing site, and results maynot be returned for 2-3 weeks. CNHS and its closely integrated CN Public Health program have an exemplary 20-year record of delivering public health interventions, including a groundbreaking Hepatitis C Virus elimination program with the University of Oklahoma Health Sciences Center, and ongoing projects with >40 rural K-12 schools. Through collaborative clinical research and molecular studies, CN and the OklahomaMedical Research Foundation have identified new immune biomarkers in tribal populations. Drawing on these existing strengths and infrastructure, Cherokee PROTECT will (1) Build infrastructure and increase FDA-EUACOVID-19 viral and antibody testing for clinical care in CNHS; (2) Enable community-based COVID-19 testing, contact tracing, and education with CN Public Health; (3) Identify barriers and facilitators to COVID-19 testing in the CN reservation to inform a tailored educational campaign to increase testing and contact tracing, and decrease spread; and (4) Implement a rigorous evaluation to ensure quality improvement and sustainability.",2020,2022,Cherokee Nation,2906085,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control | Policies for public health, disease control & community resilience",Diagnostics | Restriction measures to prevent secondary transmission in communities | Community engagement | Communication,2020 +C07209,3UG1DA050066-02S1,Community network driven COVID-19 testing of vulnerable populations in the Central US,"This C3 project, Community network-driven COVID-19 testing of vulnerable populations in the Central US, will implement and evaluate a COVID-19 testing approach that combines an evidence-based Social Network Testing Strategy (SNS) with community developed COVID-19 public health messages (SNS+). C3 will engage two disenfranchised populations across rural and urban sites in states across the Central US (TX, LA,AR, IN, IL). C3 leverages NIDA's Justice Community Opioid Innovation Network (JCOIN), the PIs' extensive community located COVID-19 testing programs, and a network of established community partnerships. The collaborative community-academic partnerships, research and engagement infrastructure, and team's leadership across JCOIN will ensure that C3 can rapidly recruit, enroll and test most disenfranchised community members, (n=2400) and through this process, accelerate any forthcoming COVID-19 public health prevention interventions. C3 focuses on two communities most impacted by COVID-19: 1) Criminal justice involved (CJI) - non-incarcerated people with previous history of arrest/jail/prison, probation/parole and drug-court attendance; and 2) Low-income Latinx - community members at 250% or below Federal Poverty Level. Both of these diverse populations, and the overlap between them, have some of the highest rates of COVID-19 infection and death in the United States. Messaging that affirms individual agency and corrects misinformation, combined with accessible and acceptable testing, is required to accelerate COVID-19 prevention for these populations. We use contextually adapted and theory-driven messages - misinformation correction and self-affirmation - to increase awareness, self-efficacy and community engagement in our adapted testing strategy -the Social Network testing Strategy (SNS). SNS is an evidence-based testing intervention that has been widely used in multiple settings with marginalized individuals (ie substance-users) who facilitate the recruitment of their social contacts into testing services. SNS combined with theory-driven, contextually appropriate COVID-19 messaging (SNS+) will address challenges to current COVID-19 testing strategies which are limited by misinformation, stigma, distrust, and limited affirmation of ability to prevent COVID-19. C3 in partnership with community will: Develop COVID-19 messages that emphasize self-affirmation and misinformation correctionfor implementation in SNS; Test the efficacy (number of network members COVID-19 tested) of a combined SNS-messaging (SNS+) intervention versus standard SNS using adaptive randomization; and Evaluate C3 implementation strategies and key implementation outcomes (ie cost) using the RE-AIM framework. The disenfranchised populations to be engaged in C3 reflect those most impacted by COVID-19 and least able to adopt COVID-19 prevention practices. C3 is ""shovel-ready"" for implementation in the short timeframe of the RADx-UP mechanism, with significant institutional commitments and community support, to ensure the procedures and interventions are tailored, feasible, acceptable and effective for at-risk communities.",2020,2022,University Of Chicago,3680904,Human Populations,Other | Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication",2020 +C07210,3R01CA226838-02S1,Tri-City Cervical Cancer Prevention Study Among Women in the Justice System,"Abstract: In response to NOT-OD-20-097, we propose to conduct supplemental research to examine the impact of the COVID-19 outbreak on cancer-related health care service utilization, health beliefs, and health disparities in an ongoing study of medically and socially vulnerable women. The parent study, Tri-City Cervical Cancer Prevention Study among Women in the Justice System (# R01CA226838) is a natural history study of cervical cancer risk among women involved in the criminal justice (CJ) system in Kansas City, KS, Birmingham, AL and Oakland, CA (N=497). We will leverage this ongoing longitudinal study to address the following Aims: 1) To examine how the COVID-19 outbreak affects cancer and other health screening and care among women at elevated risk for cervical cancer; 2) To understand how the COVID-19 outbreak and related public health mandates contribute to health disparities among women at high risk for cervical cancer. The proposed research will provide critical information about how pandemics contribute to disparities in cancer and health among poor women and women of color. Knowledge gained from this supplemental research will translate to better patient, provider, and systems-level interventions that are equipped to handle pandemics and thecancer, health, and social needs of poor women.",2020,2023,University Of Kansas Medical Center,88651,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Health service delivery",2020 +C07211,3P30AI027767-32S1,A Dynamic COVID-19 Community-Engaged Testing Strategy in Alabama (COVID COMET AL),"PROJECT SUMMARY / Abstract: Alabama is ranked as the state most vulnerable to COVID-19 by the community vulnerability index, and among the bottom 5 states in meeting SARS-CoV-2 testing targets. COVID-19 case rates are 3-fold higher in several rural counties in Alabama relative to metropolitan areas like Birmingham, with SARS-CoV-2 testing percent positivity approaching or exceeding 20% in a majority of rural counties. Meaningful community engagement in developing and implementing SARS-CoV-2 testing programs is vital to proactively address social, ethical and behavioral considerations germane to underserved communities. University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR) investigators have long-standing relationships working with clinical,community, and public health agencies to conduct innovative HIV testing and prevention studies, and are poised to act swiftly in response to the COVID-19 pandemic. A Dynamic COVID-19 Community-Engaged Testing Strategy in Alabama (COVID COMET AL) will transfer vast community-informed HIV testing knowledge to address the urgent need for rapid scale-up of SARS-CoV-2 testing among underserved rural, socio-economically disadvantaged, and Black/African American populations. COVID COMET AL is grounded in the ADAPT framework for tailoring evidence-based public health interventions for new settings and populations, and includes Assessment, Preparation, and Implementation phases. In collaboration with well-established clinical and community testing partners, regional health education centers, and additional community-based organizations,CFAR investigators will work together with interdisciplinary scientists from across campus at UAB to conduct thefollowing specific aims: Aim 1 (Assessment): Refine a data-driven, time-updated algorithm to identify the underserved rural counties most impacted by COVID-19 in Alabama, Aim 2 (Preparation): Use a community-engaged sequential mixed-methods approach to inform tailored adaptation and implementation of the COVID COMET AL strategy in highly impacted rural counties selected for implementation, Aim 3 (Implementation):Deploy the iteratively adapted COVID COMET AL strategy, which includes peer health advocates, community health workers, and venue based testing, in 3 highly impacted rural Alabama counties at a time, in two sequential waves, each lasting 6-months, and Aim 4: Evaluate the implementation process of COVID COMET AL inpartnering with community stakeholders to maximize program reach, effectiveness, and sustainability. Using aquasi-experimental, paired, comparative time series study design, temporal change in SARS-CoV-2 testing percent positivity will be compared in the 6 implementation counties relative to 6 matched control counties as the primary outcome, with testing reach, time to return test results, and time to contact tracing as secondary outcomes. Evaluation of COVID COMET AL implementation grounded in the Interactive Systems Framework will inform dissemination of this dynamic, data-driven public health testing strategy to maximize impact in addressing disparities in underserved rural communities, and will also guide COVID-19 vaccination strategies.",2020,2023,University Of Alabama At Birmingham,3323570,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Health Systems Research","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Health service delivery",2020 +C07212,1U01CA260541-01,SARS-CoV-2 correlates of protection in a Latino-origin population,"Summary: This is an initiative in support of the SARS-CoV-2 Serological Sciences, Sero Network.The rapid circulation and spread of this virus lead to a significant impact to the healthcare systems with an important societal disruption. Particularly susceptible has been the Black and Latino American origin population. In addition to the demographic and social environment, it is no know if the genetic background plays apre dominant role in that outcome. In 42 states plus Washington D.C., Hispanics/Latinos make up a greater share of confirmed cases than their share of the population. In eight states, it's more than four times greater. A great deal of effort has been deployed at a global level to contain, mitigate, and to understand the circulation, transmission, and immune response among others to SARS-CoV-2. However, there is a huge lack of knowledge particularly in the dynamic of the immune response to this virus. One additional problem is that the correlation between the antibodies titers and their neutralizing capabilities is poorly understood. Due to it, is difficult to anticipate the level of protection of an individual having specific antibodies against SARS-CoV-2. So far, the pandemic metrics, predictions, forecast models, and so on have been relying on molecular and serological assays in an overwhelming manner. The contribution of the T cells, a key player in the immune response has not been even mentioned by the organizations providing advice and guidance on the management of the pandemic.Understanding the mechanisms driving the serological, humoral, and cellular immune responses associated with the host genetic and how they correlate with protection against SARS-CoV-2 is mandatory. We will implement this SeroNet project in a Latino-African background population to determine the real seroprevalence to SARS-CoV-2. Also, we aim to study the contribution of the genetic background (HLA characterization) to the disease outcome and as susceptibility to worst clinical presentations. I order to accomplish our goals we will look in detail to the antibodies neutralizing activity, T cells immunophenotypes, cytokine profile and will integrate that data with the genetic characterization. Particular vulnerable population (individuals with comorbidities such as autoimmunedisease, immunosuppression, and obesity, medically underserved, and cancer populations) will be included inthe cohort). Our results will be compared with results obtained by other group members of the SARS-CoV-2 Sero Network.",2020,2022,University of Puerto Rico Medical Sciences Campus,1413439,Human Populations,Black | Mixed | Other,Unspecified,Unspecified,Individuals with multimorbidity | Minority communities unspecified | Other,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C07213,3UL1TR001436-06S1,Clinical and Translational Science Award (Wisconsin),"PROJECT SUMMARY/ABSTRACT for Randomized COVID-19 Testing in Vulnerable Communities and Risk Tool Creation The broad objective of this project is first to perform community-engaged research using randomized COVID-19 tests among vulnerable populations in Milwaukee County, Wisconsin, and then to use innovative empirical methods to measure infection rates and progression risk, if infected, from symptomatic infection, to hospitalization, ICU admission,and death. This project is part of the NIH RADx-UP initiative to transform health through research and discovery in COVID testing among underserved populations. The 2-year project has three specific aims. Aim 1: Use randomized COVID antibody testing of more than 23,000 persons to measure the population proportion infected with COVID and how this proportion varies over time and with patient health and demographic characteristics. Twelve partner primary care health centers and 150 churches will support community engagement to achieve target enrollments for low-income, minority and elderly populations. These populations will be oversampled to obtain more precise estimates for these high-risk groups. Aim 2: Use extensive data linkages to health care data, virus testing data, and mortality records to estimate infection rates and progression risks as a multivariate function of patient and community characteristics. A web-based risk assessment tool in English and Spanish will be created to allow individuals, families, and health care professionals to assess individual progression risk and household transmission risk and to advise individuals on risk mitigation. This risk assessment tool will be informed by the Milwaukee data and will be of value nationwide. Aim 3: When COVID vaccines become available, the risk assessment tool will be used to inform the prioritization of vaccination of higher risk individuals. Established trusting relationships withprimary care health centers and churches that serve vulnerable populations, social media outreach, community interestin COVID antibody test results, and easily accessed web-based consents, surveys, and risk assessment tools, as well asCommunity Advisory Board and focus groups input, will foster successful participation in this project. Random sampling methods will be used to estimate the population proportion infected as a function of demographic and healthcharacteristics accounting for the potential for COVID virus testing, antibody testing, or both, to result in false negative test results. Population-representative estimates will be adjusted to account for oversampling of elderly, minority, and low-income populations, and for differences in response rates to the testing offers. To estimate progression risk, the tested population will be used to create a ""synthetic"" Milwaukee. This synthetic Milwaukee information will be combined with data on deceased patients and hospitalized patients to estimate progression risks. Core empirical methods innovations include: 1) estimating the proportion of persons who are antibody negative, and either were not virus tested or were virus negative, as a function of personal and community characteristics, in order to develop a more complete measure of the infection rate; 2) using the tested subsample to create a synthetic Milwaukee which can be combined with actual data on hospitalized and deceased patients to estimate progression risks, and using multiple imputation methods to correctly estimate the uncertainty in defining the synthetic Milwaukee.",2020,2025,Medical College Of Wisconsin,3750000,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Disease pathogenesis | Community engagement,2020 +C07214,1U01CA260584-01,SARS-CoV-2 Serological Antibody Testing for Disease Surveillance and Clinical Use,"Abstract Serologic testing for presence of SARS-CoV-2 antibodies is a critical tool for understanding the epidemiology and designing control strategies for the COVID-19 pandemic. Our understanding of the epidemiology of this pandemic is primarily derived from real-time data on the number of polymerase chain reaction (PCR)-positive COVID-19 patients in outpatient and inpatient settings, and thus misses patients with asymptomatic infection or who have not had SARS-CoV-2 PCR testing. Serologic testing for SARS-CoV-2 antibodies can identify persons who have been exposed and infected with SARS-CoV-2 at any time and might be a correlate of protective immunity. This project aims to advance our understanding of SARS-CoV-2 serological testing at the individual and population-level. To achieve this we will develop and implement a large-scale, population-based, flexible platform to assess SARS-CoV-2 sero-prevalence, sero-incidence, risk of sero-conversion and longevity of antibody response in a large, integrated health system with linked rich demographic, behavioral and clinical data. For Aim 1 we will establish a community cohort of Kaiser Permanente Northern California (KPNC) members; a random sample of community dwelling persons, age 7 years and older, will be invited to participate in ongoing surveillance of antibody development to assess population-level sero-prevalence and sero-incidence. For Aim 2, we will enroll a cohort of persons who are positive for SARS-CoV-2 PCR or antibodies and will follow them prospectively with repeat SARS-CoV-2 antibody testing for immune surveillance and to determine longevity of antibody response. For Aim 3, we will establish a data-only cohort of all persons who have been diagnosed with COVID-19 disease, or had SARS-CoV-2 PCR or antibody testing; As of July15, 2020, there are about 290,000 such persons in KPNC and the number increases daily as we test ~10,000 persons per day. In this cohort, we will assess risk of SARS-CoV-2 re-infection and will have the opportunity to examine interactions with a personal history of cancer or cancer treatment and other clinical factors or comorbid conditions, to determine if these conditions influence the likelihood of development of COVID-19 or reinfection. For Aim 4, we will establish mechanisms for collaboration with other scientists in the Serological Sciences Network, including mechanisms for additional sample collection. This series of linked studies embedded in a large, integrated health system with a large number of COVID-19 patients and high SARS-CoV-2 testing capacity will enhance our understanding of the utility of commercially available, large-scale SARS-CoV-2 antibody testing for population-level and individual-level disease control.",2020,2022,Kaiser Foundation Research Institute,1384008,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C07215,3R01CA220591-03S1,Evaluation of Smoke-Free Housing Policy Impacts on Tobacco Smoke Exposure and Health Outcomes,"ABSTRACT. By mid-June, 2020, COVID-19 associated hospitalization rates among Hispanic/Latino and African-American/Black persons in the United States were 4 and 5 times greater than that of non-HispanicWhite persons. New York City (NYC) became the epicenter of COVID-19 early in the epidemic and disturbing patterns of COVID-related disparities rapidly emerged. The Rapid Acceleration of Diagnostics for Underserved Populations (RADx-UP) initiative supports supplements to individual NIH awards to increase COVID-19 testing among underserved populations. For this proposal, we leverage the infrastructure of a current project in NYC(NCI R01CA220591 ""Evaluation of Smoke-Free Housing Policy Impacts on Tobacco Smoke Exposure"") and longstanding partnerships between the NYC Housing Authority (NYCHA), the NYC Health Department. The NYC public hospital system responsible for contact tracing (NYC Health + Hospitals) and a robust set of community partners to execute a data-informed, community-engaged research to develop and test strategiesto increase adoption of COVID-19 testing among NYC public housing residents. NYCHA is the largest public housing authority in North America, with more than 400,000 official residents living in 15% of the nation's public housing units. Median family income is $20,000, and approximately 90% of NYCHA residents are either black or Hispanic. Our aims are to: 1) Develop a sustainable community engagement infrastructure to guide current and future deployment of evidence-based COVID-19 testing and vaccination options for NYC Public Housingresidents; 2) Quantify inequities in COVID testing and SARS CoV-2 infection among Public Housing residents; 3) Engage NYCHA residents and community based organization partners in primary data collection and analysis to understand barriers to testing, isolation and follow-up care; and 4) Test community-informed strategies to increase testing uptake. Specifically, we aim to conduct a cluster randomized controlled trial totest the added value of adding navigation services to teams of community health worker (CHWs) and residentnavigators offering a menu of COVID-19 testing referral options. We will compare impacts on reach,acceptability and adoption of COVID-19 diagnostic testing. By capitalizing on strong partnerships, robustmunicipal data sources that support real-time prospective surveillance, and a rapidly expanding array of testing initiatives, this implementation study offers an unparalleled opportunity to identify effective strategies to reduce disparities in COVID risk and health outcomes in a large, high-need population. Findings will be used to develop guidance for implementing testing strategies in multi-unit and public housing settings nationally.",2020,2022,New York University School Of Medicine,774729,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified,Other,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Impact/ effectiveness of control measures | Disease surveillance & mapping | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement",2017 +C07216,3UH3AI133669-04S1,LITE CONNECT: Addressing testing gaps and epidemiologic disparities of COVID-19 among transgender people in the United States,"Abstract: Transgender (TG) people are a NIH-designated health disparities population with high morbidity and mortality across multiple health conditions, including HIV infection, mental health, and substance use. These conditions are a product of and exacerbated by historical and ongoing discrimination and inequities in access to healthcare. In early 2020, Severe Acute RespiratorySyndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) was recognized as a global pandemic. To date, no data exists on COVID-19 disease in TG people.There is an urgent need to understand the burden of COVID-19 disease, investigate its impacton other health conditions and vulnerabilities burdening TG populations, and identify future public health intervention targets. The current proposal aims to fill this gap. To accomplish these goals, disparities in access to testing among TG people must be identified and mitigated. The parent LITE study enrolled a baseline sample of more than 1500 TG women in the eastern and southern U.S. to assess HIV risk across 24 months of bio behavioral follow-up using technology-enhanced, digital methods of data capture. Leveraging the LITE infrastructure and in partnership with two community-based organizations, we aim to develop LITE-CONNECT, a rapid, community-engaged mixed-methods assessment that will enroll over 2,000 TG men and women across eastern and southern U.S. The objective of this supplemental study is to characterize access and barriers to COVID-19 testing, provide access to and evaluate the use of home-based COVID-19 antibody testing to identify past infection and potential immunity, connect TG men and women to available community-based COVID-19 testing and support services, and identify community-based solutions to support access to COVID-19 testing, interventions, and care among TG people. Results from this study will be rapidly used to inform community-based efforts and national COVID-19 response that is inclusive of TG people. The proposed research will provide critical and timely insights about COVID-19 disease in TG people in a space in which almost no information currently exists. Early identification of disparities in COVID-19 morbidity and in access to COVID-19 testing and care is critical to ensuring access to services as the pandemic continues. We will leverage our existing infrastructure and community collaborations to gather new data, including unprecedented data from TG men, to guide urgently needed interventions to improve and optimize the health andwellbeing of TG people in the context of the COVID-19 pandemic.",2020,2022,Johns Hopkins University,1443647,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Gender,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Impact/ effectiveness of control measures | Disease surveillance & mapping | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Indirect health impacts",2020 +C07217,1U01CA260513-01,"Pre-exposure Immunologic Health and Linkages to SARS-COV2 Serologic Responses, Endothelial Cell Resilience, and Cardiovascular Complications: Defining the mechanistic basis of high risk endotypes.","Abstract: The objective of this proposal is to understand the immunologic foundations of heart disease which can occur as a result of COVID19. Cardiac impairment, when it develops is often fatal, and our hypothesis is that the maintenance of endothelial function is critical to surviving the protracted nature of COVID19 pneumonia, especially in those with reduced or delayed antibody responses. Our first aim will be to analyze those differences in immune function which pre-date infection but appear to impact the risk of fatal COVID. This will be done by enrolling those at high risk for developing COVID19 (frontline healthcare workers), and performing serially assessments of their immunologic function if they develop COVID. We will specifically investigate the mechanisms that link pre-infection inflammatory pathways to protective serologic responses and symptom severity and recovery. Our second aim will be to perform in vitro experiments to assess the requirements for endothelial cell dysfunction and infectivity. We will compare various inflammatory and cardiovascular stimuli which seem to play a role in promoting COVID19-related cardiovascular complications. Our third aim is to characterize immune cells, endothelial cells, and cardiomyocytes in heart tissue from those with COVID19-induced left ventricular dysfunction. Using single cell sequencing techniques, we will determine cellular and molecular signatures that characterize the micro environment of the COVID19-affected heart, compared to appropriate controls. Our conceptual model is that pre-existing immune dysfunction 1) reduces the efficiency of neutralizingantibody responses, and 2) in conjunction with cardiovascular disease risk factors, induces endothelial downregulation/depletion of nodal regulators which protect against inflammatory insults. This renders endothelial cells unable to withstand COVID-specific stimuli. Once completed, this study will provide thenecessary information to improve the identification of those at risk for COVID-related heart disease and developrationale approaches to improve the improve survival in the setting of COVID.",2020,2022,Case Western Reserve University,1358848,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C07218,3R01CA240080-02S1,Advancing Palliative Care in Northern Plains American Indians,"Abstract: COVID-19 has created unparalleled challenges to the health of the most vulnerable communities in the US.Although these disparities are multifactorial, addressing inadequate access to and uptake of COVID-19 testing will be critical for optimizing COVID-19 response in these communities. The Lakota tribal communities in the Great Plains are some of the most disadvantaged communities in the US with life expectancy nearly 20 years shorter than US average and a staggering burden of acute and chronic disease. Although the US governmentis required by treaty agreements to provide health care to the Lakota tribes, inadequate funding of the Indian Health Service (IHS) on top of insufficient staffing and infrastructure, lack of cultural sensitivity, and extensive history of trauma and abuse have led to widespread distrust and dissatisfaction with the IHS. Furthermore, high levels of poverty and unemployment, lack of other forms of health insurance and long travel distancesmean that other health care options are out of reach of most tribal members. Given this reality, the effectiveimplementation of COVID-19 testing requires a tribally driven effort to understand the perspectives of tribal members on testing and the downstream implications of testing, and to ensure that testing strategies and other COVID related interventions are grounded in the cultural values, traditions and experiences of the Lakota tribes. Over the last 6 years, we have developed a multidisciplinary, tribally-driven collaboration to advancethe health of Lakota tribes that brings together organizations in South Dakota (Great Plains Tribal Chairmen'sHealth Board, Avera Health/Walking Forward, South Dakota State School of Nursing, Indian Health Service), the Cheyenne River, Pine Ridge and Rosebud Sioux tribes and Mass General/Harvard. In this application, we propose to build upon this collaboration to conduct a two phase study to: (1) understand the social, cultural andeconomic factors driving use of COVID-19 testing in these tribes; (2) determine alternative strategies for delivering testing in these communities, and (3) expand the Great Plains Lakota Health Research Collaboration(GPLHRC) to develop a sustainable platform for creating evidence to support Lakota COVID-19 response,collaborate with other efforts to improve COVID-19 testing among vulnerable populations, and contribute to theRADx-UP network. Informed by our community advisory board and conceptual frameworks, we will use an innovative methodological approach integrating semi-structured interviews and discrete choice experiments to develop robust insights into how to design key components of test delivery. We will focus on viral testing (and downstream issues of contact tracing/ quarantine), but study results will inform future implementation of vaccination and other strategies. Products will include strategies to increase acceptability and accessibility of testing in Lakota communities, an innovative and adaptable ""tool-kit"" for assessing the impact of future COVID-19 response strategies, a novel ""community detailing"" model for increasing engagement in COVID-19 response, and new knowledge about the role of key cultural, social, and economic factors in access to healthcare among Lakota tribes.",2020,2022,Massachusetts General Hospital,560218,Human Populations,Other,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2019 +C07219,3R41HG010978-01S1,Secure Homomorphically Encrypted National Registry of COVID-19 Recovered Plasma Donors,"PROJECT Summary: Treatment with convalescent plasma (CP) was recently approved by the FDA for seriously ill patients ofCOVID-19. There are many institutions and hospitals that have implemented CP programs, but they all face the challenge of finding sufficient and appropriate donors. The constraints of matching, imbalances in supply and demand, and privacy concerns pose several challenges to engage donors. Considering multiple stakeholders (patients, donors, hospitals), we will develop new algorithms based on multikey homomorphic encryption to protect the privacy of patients and donors, with additional functionality to simplify the registration process, and conduct optimization for plasma donation (of patients who recovered from COVID-19). We are dedicated to the public good and will make freely available the code / resources developed within the framework of this project. If we succeed, our project will build a secure national registry for potential plasma donors and may save many lives.",2020,2021,Elimu Informatics Inc,220723,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2020 +C07220,3P50CA244433-02S1,Implementation Science Center in Cancer Control Equity: A Competitive Revision to Accelerate COVID Testing in Vulnerable Communities,"Abstract: This competitive revision submitted to the RADx-UP Initiative (NOT-20-121) aims to extend the infrastructure ofour P50 Implementation Science Center for Cancer Control Equity (ISCCCE) to accelerate COVID testing in 9 hotspot communities in MA. ISCCCE is a strong partnership with the Massachusetts League of Community Health Centers, in which we co-design studies to increase implementation of evidence-based practices focused on equity. Together we are extremely well-positioned to extend our community-engaged efforts toCOVID-19 testing, and to build an infrastructure that will support future COVID-related mitigation and prevention efforts in the vulnerable communities that our community health centers (CHCs) serve. This project will include 6 community health center- community partnerships in nine vulnerable communities that continue to be COVID hot spots. These communities collectively have 1.3 million residents. Partner CHCs currently focus on COVID-19 testing for diagnostic purposes in symptomatic individuals, with limited outreach testing in high-risk communities. This project will expand the scope of testing to include prospective surveillance activities using dedicated testing and outreach teams. Accelerated testing efforts will be focused on CHC patients and community members who have significant social and medical vulnerabilities to COVID, per the NOSI, including those living in congregate housing, people experiencing homelessness, those with substance use disorders, low wage essential workers, and those with limited English proficiency. The partnership is well-integrated into the State's testing and contact tracing strategy, and well-positioned to leverage those resources. We draw on our strongly community-engaged, equity-focused approach to implementation, and on Mass League's extensive experience in HIV testing and contact tracing. We will use an interrupted time series design to evaluate the impact of the enhanced outreach efforts on testing rates overall and on priority populations in the context of different phases of re-opening and restrictions.We will also use an exploratory sequential mixed methods approach to conduct a series of community-engaged pilot studies to address key barriers to testing and different approaches to return of results. Our Human Participant Research Unit, co-led by academic and community-based investigators, will guide th epartnership's work through an ethics and equity lens. We will support the CHC-community partnershipsthrough our Testing Capacity and Innovation Team, which will provide infectious disease expertise and technical guidance on COVID testing. Our Community Communications Team will use educational andcommunication design strategies to develop culturally and linguistically appropriate materials to support the testing activities.",2020,2022,Harvard University,3432338,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Research to inform ethical issues | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Community engagement | Communication",2020 +C07221,3P30DA011041-23S1,A Nurse-Community Health Worker-Family Partnership Model to Increase COVID-19 Testing in Urban Underserved and Vulnerable Communities,"PROJECT SUMMARY/ABSTRACT New York City (NYC) is a global epicenter of the SARS-CoV2/COVID-19 pandemic, with 223,000 cases and more than 25,000 deaths. Neighborhood-level disparities in cases and deaths in NYC can be explained by socioeconomic and racial/ethnic characteristics, where Latinx and Black New Yorkers and those living in highpoverty neighborhoods are 1.5 times more likely to test positive and more than twice as likely to die as a resultof COVID-19. The community of Mott Haven is located in the South Bronx - one of the poorest congressionaldistricts within the continental United States. Mott Haven is highly diverse (73% are Latinx and 24% are Black),and the COVID-19 mortality rate is higher than NYC as a whole - an epicenter within an epicenter. Yet, although Mott Haven is clearly a priority community for COVID-related prevention, detection, vaccination, and treatment initiatives, so far fewer than 2% of residents have been tested. COVID-19 secondary attack rates are highest in households, varying between 12 - 38%. This led us to propose a COVID-19 testing and mitigation intervention in public housing households in Mott Haven, which are characterized by crowding, intergenerational co-residence, and a high proportion of low wage ""essential workers"" who leave the home for work even during lockdown periods. We will evaluate the effectiveness of an innovative Nurse-Community Health Worker (CHW)-Family Partnership intervention designed to promote COVID-19 testing uptake, adoption of COVID-19 control measures, and mutual aid capacity at the household level. Our intervention is adapted from the Nurse-Family Partnership model, which has been shown to be effective and cost-effective in improving maternal and child health outcomes in high-poverty, racially- and ethnically-diverse communities. CHWs will provide culturally-appropriate support to families, addressing stigma, medical mistrust, and other common barriers to engagement in healthcare. We propose a 2-arm randomized controlled trial, in which 270 households (810 individuals) will be randomly assigned (2:1) to either the experimental group of families who will receive the Nurse-CHW-Family Partnership intervention and the offer of in-home testing and influenza vaccination, or the treatment-as-usual control group referred to free testing and flu vaccination located within walking distance. Participants in both arms will be assessed at baseline and monthly for 12 months. Findings from this study will provide an evidence-base to inform current and future public health initiatives related to COVID-19 mitigation in other high-risk settings. Sustainability will be addressed by building local capacity and expertise among participants, CHWs and CAB members, and partnering with them to develop the community's best practices for COVID-19. Should it prove to be effective, our intervention can be tailored to increase testing and other COVID-19 control measures in other settings of vulnerability and disadvantage.",2020,2022,New York University,3643065,Human Populations,Black | Other,Adults (18 and older),Urban Population/Setting,Minority communities unspecified,Nurses and Nursing Staff | Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication",1998 +C07222,3U01AA020776-10S1,COVID-19 Pandemic-Related Changes in Alcohol use among Persons with HIV,"The COVID-19 pandemic and the resulting stay-home restrictions are likely to drastically impact alcohol use, due to the resulting psychological distress, anxiety, boredom, and social isolation. We propose here to examine changes in alcohol use and the impact on antiretroviral (ART) adherence in ongoing cohorts of people with HIV (PWH) with histories of alcohol use during and after the pandemic in the US (Boston) and Uganda (Mbarara). In the US, there has been a surge in alcohol sales, weekday drinking, and references to alcohol use on the internet. The impact of the COVID-19 restrictions in Uganda is not yet known. There are anecdotal reports of decreased drinking due to low accessibility of alcohol, but drinking may rebound when restrictions are lifted. PWH have high levels of alcohol use and other mental health co-morbidities, and therefore may be at high risk for increases or relapses in any setting. Research is hence urgently needed to quantify pandemic-related changes in alcohol use among PWH with heavy alcohol use in various settings. In addition, alcohol use is a consistently strong risk factor for poor antiretroviral (ART) adherence and poor viral suppression; changes in alcohol use are associated with poor HIV viral control; and the impact of the stay-home measures on medication adherence is unknown. Social desirability and recall bias impede investigations using self-report of alcohol and medication adherence, but drug levels and direct metabolites of alcohol consumption serve as objective markers, yielding quantitative results for dose-response investigations, with long half-lives for retrospective measurement. Thus, we will measure prior alcohol use using alcohol metabolite phosphatidylethanol (PEth) in dried blood spots (DBS) (measuring 2-3 weeks' alcohol use) and ethylglucuronide (EtG) in hair (measuring 1-3 months' alcohol use), as well as ART concentrations in hair(measuring weeks to months' ART), to supplement self-report. We will leverage ongoing cohorts that are part of the NIAAA-funded URBAN ARCH consortium, as well as the UCSF Hair Analytic Laboratory (HAL), with vast experience measuring ART in hair, to adapt existing laboratory protocols to hair EtG testing, and to develop automated DBS processing for PEth. We aim to (1) determine the proportion of drinkers with regular heavy alcohol use before, during, and after stay-home restrictions among PWH in Uganda and the US (n=125each), and characterize changes in drinking in each cohort; (2) examine whether ART levels in hair and viral suppression rates change from pre-COVID to after stay-home restrictions are lifted, and the role of changing alcohol use; and (3) adapt existing HAL ART hair assay protocols for analysis of EtG for the above aims, and to develop and validate automated DBS processing to create high-throughput PEth testing. This work will advance our understanding of the impact of the COVID-19 pandemic on alcohol use and its role in ART adherence and viral suppression, while expanding alcohol biomarker testing capability in specimens which are easy-to-collect and ship to improve objective monitoring of alcohol use into the future.",2020,2021,University Of California-San Francisco,181237,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Africa | Americas,,,,United States of America,United States of America | Uganda,"Secondary impacts of disease, response & control measures",Indirect health impacts,2011 +C07223,3P30ES023513-06S1,"ORALE COVID-19!: Organizaciones para Reducir, Avanzar y Lograr Equidad contra el COVID-19 (Organizations to Reduce, and to Advance, and Lead for Equity against COVID-19)","Abstract: The COVID-19 pandemic has disproportionately affected the already underserved Latinx communities. The overall goal of the proposed testing research project is to decrease disparities in the morbidity and mortality patterns for COVID-19 through engaged partnerships with several communities in central California that are both historically underserved and vulnerable to COVID-19, namely the Latinx. These communities currently are experiencing infection rates that are three times higher than whites, and are among the highest in the U.S.They also are among the most socially and economically disadvantaged, have high rates of co-morbidities such as diabetes and asthma, live in overcrowded housing, and reside in some of the most polluted areas of the country. A high proportion are undocumented and employed in food production, especially farm labor,performing essential work that has been a backbone of the California economy, while simultaneously being marginalized. The proposed research will build upon long-term existing partnerships with an array of community-based organizations and trusted leaders in Latinx communities to develop interventions that address the barriers to SARS-CoV2 diagnostics, as part of a larger strategy to reduce transmission and control the pandemic in the Latinx population of central California. Because of the dynamic changes in incidence,shifting hubs of transmission, and policy changes from authorities, a comparator trial of different community-developed interventions is needed to provide information on which actions are feasible, acceptable, and effective. Hence, comparisons will be made between the Latinx population and whites in the same counties,and among Latinx persons from counties having different interventions, with adjustment for infection incidence rates and trajectories, as well as local policy changes and government interventions. We will pursue the overall goal with the following specific aims: 1) Determine the epidemiology of COVID-19 infections, COVID-19 related mortality, and SARS-CoV-2 testing rates in selected Latinx and white non-Latinx communities of targeted California counties, 2) Develop strategies to increase testing and reduce rates of infection in the targeted areas in collaboration with community partners and, 3) Disseminate information and knowledge gained from this project back to partnering communities, other grantees from this and other COVID-19 initiatives by full participation in RADx-UP Coordinating Data and Collection Center (CDCC), to the broad public, and to policy-makers. Experience and knowledge gained through achievement of these aims will set a firm foundation forsubsequent research on COVID-19 and health disparities and will help to prepare communities to meet thechallenges of future public health crises.",2020,2022,University Of California-Davis,3750373,Human Populations,White | Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease susceptibility | Disease surveillance & mapping | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication",2020 +C07224,3UL1TR002733-03S3,The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve Health,"PROJECT SUMMARY Ohio includes a very diverse population, with many minority, underserved, and vulnerable communities (MUVP).The need to increase testing in Ohio's MUVP is great - testing rates are only at 2.0 per 1000, with positivity rates indicating active community spread. With rapidly rising infection rates, ways to curb infection and morbidity/mortality are needed, especially in the most vulnerable populations. This RADx-UP Initiative Large Network proposal, RADx-UP Ohio, leverages the vast community partnership networks of the Ohio Center for Clinical and Translational Science Award and the OSU Comprehensive Cancer Center to identify reasons for and intervene to reduce disparities in COVID-19 education, testing, contact tracing, follow-up and treatment among MUVP in Ohio in a bi-directional academic-state-community partnership. This complements the work of Ohio Department of Health (ODH) emergency response to this pandemic. Our research process is guided by a socio-ecological model based on the Social Determinants of Health, the Proctor Model for Implementation Science 2 and a Community-Based Participatory Research (CBPR) framework and prior preliminary work of the team, using an implementation science framework and overall program evaluation. The specific aims are to: Aim 1. Implement a multi-level intervention, built on effective interventions of the team, to increase the impact of COVID testing in MUVP in 12 selected counties informed by community partner input that will increase uptake of COVID-19 testing, knowledge of COVID-19 testing and results, and follow-up including contact tracing for positives. Aim 2. Assess the impact and sustainability of the intervention in different MUVP in Ohio. Aim 3. Interact with public health entities to disseminate successful strategies. The interventions will be culturally-appropriate and tailored to the needs of each MUVP in the 12 selected counties using an implementation science design, with counties randomized in a 3-wave step wedge design. RADx-Up Ohio includes the following Units: Community Engagement and Intervention; Testing; Statistics and Data Management); Human Subjects, and Evaluation. RADx-UP Ohio uses a hub and spoke model where the units provide expertise to support the activities of the 4 regional teams, each of which includes CHWs from each of the 3 individual counties with at least one community stakeholder to provide community context and ensure authentic partnerships are maintained. We will work closely with the RADx-UP Imitative components to successfully complete the aims.",2020,2023,Ohio State University,3643333,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication",2020 +C07225,3R01DA045556-04S1,Juntos (Together): A community led approach to enhance to Covid-19 testing among vulnerable Latinos,"PROJECT SUMMARY Latinos are among the most heavily impacted communities by the COVID-19 pandemic in the US, with more than 3 times higher rate than non-Hispanic whites. To address this disparity, this team of investigators andcommunity partners has established a multi-pronged approach that leverages the skill set of trusted bilingual/bicultural peer navigators (or promotoras) to address social determinants of health (SDOH) that create barriers to testing (such as lack of insurance, immigration status, stigmatization or loss of job/income), and to expand access to free COVID-19 testing in community settings. Our preliminary findings show that leveraging the promotora model for timely delivery of results (within 48 hours), paired with rapid linkage of COVID-19 positive patients to critical services (including clinical follow-up, food delivery, cash assistance, and/or isolation hotel), and referral of contacts for testing, increased acceptability and uptake of COVID-19 testing in a heavily impacted Latino community. The overall goal of this Phase I Testing Research Project called Juntos (Together) is to work closely with our community partners to systematically evaluate and refine current COVID-19 testing strategies, and to implement and evaluate innovative customized strategies to rapidly increase reach, access, acceptance, uptake, and sustainment of FDA-authorized/approved diagnostics (especially viral tests) for this highly vulnerable and health care marginalized community. Leveraging community partnerships and prior experience implementing an HIV testing campaign, we will develop and evaluate a customized Juntos COVID-19 testing campaign to address specific common concerns in the Latino community and link users to existing Johns Hopkins COVID-19 community testing sites and to new options, including home-based and/or self-testing kits and rapid tests (Aim 1). To assess the overall impact of the Juntos COVID-19 Testing Project, we will rely on the latest in causal inference methods for evaluating population-level health interventions and implement a synthetic control analysis to compare testing uptake and positivity rate among Latinos in Baltimore City (intervention site) as compared to control zip codes across Maryland. (Aim 2). Finally, informed by Consolidated Framework for Implementation Research (CFIR) and RE-AIM framework, we will assess the implementation determinants, mechanisms, and outcomes of existing and novel Juntos testing interventions to inform future broad-scale implementation (Aim 3). We have assembled a multi-disciplinary team withmethodological expertise in implementation science, community-based research, and laboratory medicine, andhave a mature and long-standing collaboration with our partners at Esperanza Center, Casa de Maryland, theMayor's Office of Immigrant Affairs, and religious leaders. Our team is enthusiastic to propose this implementation study to enhance access to testing for the Latino community, and will actively coordinate and share data and protocols with other grantees, the CDCC, and other research supported by the RADx-UP program.",2020,2022,Johns Hopkins University,1570444,Human Populations,Other,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Research to inform ethical issues | Policies for public health, disease control & community resilience","Impact/ effectiveness of control measures | Supportive care, processes of care and management | Research to inform ethical issues in the Allocation of Resources | Approaches to public health interventions | Community engagement | Communication",2020 +C07226,3U54CA132384-10S1,Communities Fighting COVID!,"PROJECT Summary: The novel SARS-CoV-2 continues to spread in the United States, with almost 5 million confirmed cases of andover 150,000 deaths. Given observed disparities in morbidity, hospitalization, and mortality across race, ethnicity,and socioeconomic status, there is a great need to increase testing access and uptake with rapid return of test results. We propose a community health worker (CHW)-led approach to facilitate COVID-19 testing for underserved populations, with a focus on increasing testing access, uptake, and impact among Latinx, African American, Filipino, and immigrant communities using different testing implementation strategies. Our project will utilize existing COVID-19 contact tracing and community partner infrastructure to reach individuals aged 12 and above exposed or at high-risk of COVID-19 exposure who may be less able to test. We will use a cluster randomized crossover trial to test mobile and home-based testing strategies for increasing testing uptake among contacts, referred high-risk friends and family, and the broader community. Our specific aims are to: 1) Implement COVID-19 testing integrated into community health worker contact tracing home visits and compare the subsequent uptake of testing for referred high-risk friends and family in a mobile testing vs. home-based testing approach; 2) Using a community-led rapid cycle research process, identify effective strategies to promote uptakeof COVID-19 testing through mobile/pop-up testing for Latinx, African American, Filipino, and immigrant populations exposed or at high risk of exposure to COVID-19 who are not accessing testing; 3) Gather CHW and community insights to establish best practices for future scale-up and sustainability. We expect to test over 40,000 individuals through these efforts. The project will contribute to health disparity reductions in COVID-19 morbidity and mortality and produce high impact through the our core strengths in drawing on local knowledge,the team's existing community partnerships, use of culturally-competent community healthcare workers, point-of-care rapid and inexpensive testing, and the use of real-time geospatial data from our contact tracing program to prioritize locations for mobile pop-up testing. Our focus on underserved populations with high COVID-19 exposures without prior testing access will inform both future testing and vaccination efforts.",2020,2021,San Diego State University,3876170,Human Populations,Black | Other,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication",2007 +C07227,1U01CA260508-01,High-Throughput Dried Blood Spot (HT-DBS) Technologies in SARS COV-2 Serology and Vaccinology,"Project Summary: As the COVID-19 pandemic continues to spread across the United States it is imperative that we implement technologies to screen large swaths of the population for the presence of antibodies to SARS-CoV-2. Serological surveillance not only affords a measure of virus exposure within a community at large but also provides information necessary to predict outbreak dynamics. Furthermore, as our understanding of how humoral factors contribute to controlling (and possibly exacerbating) COVID-19, it will be essential to have methods in place to measure the ""quantity"" and ""quality"" of antibodies associated with both natural SARS-CoV-2 exposure and candidate SARS-CoV-2 vaccines. This U01 proposal seeks to advance the use of dried bloodspots (DBS) in conjunction with a Luminex-based microsphere immunoassay (MIA) to enable high-throughput (HT) population-wide serological surveillance for SARS-CoV-2. Specifically, the proposal will expand the HT-DBS assay to capture the breadth and complexity of SARS-CoV-2 antibody responses following natural infection, and develop a high-throughput competitive immunoassay (CIA) as a surrogate measure of SARS-CoV-2 neutralizing antibody titers in DBS. The proposed platform technologies to be developed at theWadsworth Center will contribute directly to NCI's mission to ""... develop, validate, improve and implementserological testing and associated technologies..."" to address the COVID-19 pandemic.",2020,2022,Wadsworth Center,1153230,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C07228,1U01CA261276-01,Enhancing racial and ethnic diversity in COVID-19 research participation through storytelling (COVIDstory),No abstract available.,2020,2022,University of Massachusetts Chan Medical School,2043738,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Community engagement",2020 +C07229,3R01AA024409-05S1,Role of Alcohol Disparities in HIV Risk among Sexual Minority Youth,"PROJECT Summary: The coronavirus (COVID-19) pandemic has had widespread social, psychological, and economic repercussions in the United States, along with devastating morbidity and mortality. However, these effects have not impacted all populations equally. Surveillance data show that racial/ethnic minorities, including Black, Latinx, and Indigenous populations, have been disproportionately burdened by both the disease and its financial and social consequences. Similarly, sexual and gender minority (SGM) groups, while not captured innational surveillance data, experience high levels of vulnerability, suggesting that they too may be experiencing higher rates of infection and related ramifications of COVID-19. Crucially, as the pandemic has continued todevelop in the US, a greater number of cases have been identified among youth and young adults (YYA) aged 14-24 years, a population previously thought to be at low risk. Given the high mobility and lower perceived riskof this population, this may result in larger outbreaks not only within YYA, but also overall and in additional vulnerable groups. Therefore, understanding and increasing testing and preventive behaviors among YYA, especially vulnerable SGM YYA (SGMY) and racial/ethnic minority YYA (REMY), is necessary to stop further COVID-19 spread. Unfortunately, COVID-19 impacts, testing, and preventive behaviors in this population have remained markedly understudied. Critically, disparities in testing and preventive behaviors are highly influenced by outside factors. For example, experiences of stigma, at the individual, interpersonal, and structural level, may impact care engagement and prevention among marginalized populations. Furthermore, policy-level factors, including availability of tests, healthcare, governmental messaging, and re-opening patterns, are also likely to influence rates of testing and rates of infection. As such, given the dearth of information surrounding COVID-19 among SGMY and REMY, and the rising rates of infection in these groups, this project will use a geographically diverse quantitative survey to assess patterns and disparities in COVID-19 testing and preventive behaviors longitudinally across 6 months, as well as the impact of multilevel factors,including stigma and policy. Informed by the results of this survey, and guided by the Information, Motivation,and Behavioral Skills (IMB) Model, we will use a mixed-methods approach to iteratively develop a community engaged, health messaging intervention tailored towards SGMY and REMY to increase testing and preventive behaviors, provisionally titled Prev_Cvd. This text messaging intervention will be pilot testied by 100 REMYand SGMY to refine content and determine feasibility and acceptability. Given the lack of messaging guidelines for this population, this will be the first evidence-based messaging intervention for COVID-19 prevention among YYA. Developing and pilot testing such an intervention with active input from the community will allow for the intervention, if effective, to be rapidly scaled up and widely implemented to address disparities in COVID-19 among YYA and reduce overall transmission.",2021,2021,Northwestern University At Chicago,600928,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Indigenous People | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Communication | Indirect health impacts,2016 +C07230,3R37CA245716-01A1S1,Addressing Low-Income Housing Resident Mistrust in COVID-19 Guidance,"Project Summary Ongoing engagement of low-income housing residents suggests that widespread mistrust of information about COVID-19, particularly when received from public housing authorities, has contributed to low compliance with public health guidance in these communities. In particular, recommendations for COVID-19 testing are met with skepticism and suspicion. We have received similar feedback about potential vaccination when/if a COVID-19 vaccine is developed-in addition to mistrust in COVID-19 messaging, persistent concerns about exploitation in research seem to be negatively affecting attitudes toward participation in certain types of related activities, especially when a blood draw or injection is involved. Principles and approaches from community-based participatory research guide this study. In Aim 1 we investigate why low-income housing residents report poor compliance with public health guidance,including COVID-19 testing. We will determine whether residents do not understand COVID-19 guidance (particularly whether they are able to generalize guidance from one setting to another) or if they understand, but instead choose not to comply. In Aim 2 we will assess telehealth as a potential tool for addressing low-income housing resident mistrust in COVID-19 guidance. In our preliminary work, physicians with whom residents have established relationships were considered the most trustworthy source of COVID-19 information. Unfortunately, residents commonly report that COVID-19 has disrupted how they receive medical care. In Aim 3 we develop community-informed strategies to address resident concerns about COVID-19 testing and to make testing more relevant to their needs. We will begin by exploring strategies to overcome the impact of privacy concerns of residents on the provision of services or other benefits offered or coordinated by PHAs. Other barriers will be addressed as they emerge.",2020,2025,Eastern Virginia Medical School,304629,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy",2020 +C07231,3P42ES010337-19S2,Harnessing Technological Innovation and Community-Engaged Implementation Science to Optimize COVID-19 Testing for Women and Children in Underserved Communities,"ABSTRACT San Ysidro sits on the US-Mexico border and has a linguistically and ethnically diverse (91% Latinx) population,which is impacted by significant economic and health disparities. 33% of household incomes are less than $29K/yr, and there is a high rate of the comorbidities linked to poor COVID-19 outcomes. The San Ysidro Portof Entry is one of the largest international border crossing facilities in the world, with an estimated 50,000 vehicles and 25,000 pedestrians crossing into the US each day. A young and culturally diverse community of 27K residents, San Ysidro has the largest number of pre- and middle school children in San Diego. Physically removed from the major testing centers in San Diego, the response to the pandemic in San Ysidro has been hampered by a shortage of COVID-19 testing coupled with long test result turnaround times. The San Ysidro community has been disproportionately impacted by COVID-19, with the highest incidence of COVID-19 cases in San Diego County. Although children with COVID-19 infection generally have good outcomes, closures of public schools and associated activities have deprived many children of important educational and nutritionalresources. Fear of infection has resulted in marked drops in prenatal and pediatric visits and lower childhood immunization rates. Since regular prenatal and pediatric care is associated with optimal pregnancy and child health outcomes, ensuring the safety of clinics is a high priority. San Ysidro Health is a federally qualified health center and the largest healthcare delivery system serving San Ysidro residents, including the uninsured and underinsured. The recommended schedule of prenatal and pediatric visits (for surveillance of maternal and fetal well-being, monitoring of childhood development, and provision of immunizations) provides an excellent opportunity to engage families in COVID-19 testing within an otherwise hard-to-reach population. At UC San Diego, scientists and engineers have developed a new high-throughput FDA authorized robotic testing work flow that provides an inexpensive, accurate, and rapid detection of COVID-19 infections. As part of the UC San DiegoSuperfund Research Center (SRC), we have in place extensive Community Outreach and Engagement with several South San Diego regions and have established strong partnerships with these communities, including those at San Ysidro. We will rely on a mixed methods, multi-level community-engaged approach to gather information on the barriers and facilitators of the delivery and uptake of COVID-19 testing at the individual, organizational and community levels. In partnership with our diverse Community and Scientific Advisory Board,we will use co-creation and appreciative inquiry approaches to inform the development, implementation and evaluation of a set of contextually relevant strategies that will accelerate the broad delivery and uptake of COVID-19 testing among pregnant women and children and scaling across the entire San Ysidro community. The overarching goal of extensive and rapid COVID-19 testing is to eliminate the disparities experienced by underserved communities in testing access and ultimately in morbidity and mortality from COVID-19.",2020,2022,"University Of California, San Diego",3759967,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Health Systems Research","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Health service delivery",2000 +C07232,3UG1DA050072-02S3,COVID-19 testing and prevention in correctional settings,"PROJECT SUMMARY Correctional settings account for 39 of the 50 largest outbreaks of COVID-19 in the US to date. Transmission of the COVID-19 virus (SARS-CoV-2) is amplified in correctional settings due to restricted access to sanitizing supplies, personal protective equipment and diagnostic tests, close congregant living conditions, and exposure to correctional staff who unknowingly transmit the infection from the community. Incarcerated people are also more likely to die from COVID-19 compared to the general population. Therefore, there is an urgent need for the development and implementation of long-term COVID-19 testing and prevention strategies targeting incarcerated populations and correctional staff. However, there are also long-standing ethical and pragmatic concerns unique to corrections, which may present as barriers to the successful implementation of prevention strategies. Prior work has not explored the ethical, legal, and social barriers to COVID-19 testing and vaccine administration in corrections, especially centered around the values, preferences, and needs of those who work and live in correctional facilities. Until this knowledge gap addressed, it will be difficult to reduce COVID-19 morbidity and mortality in correctional facilities. In response to NOSI-20-121, and as a supplement to aNIDA Justice Community Opioid Innovation (JCOIN) consortium's grant (1UG1DA050072-01), the overall objective of our study, ""COVID-19 Testing and Prevention in Correctional Settings,"" is to increase the reach, access, uptake, and impact of COVID-19 testing and mitigate the impact of COVID-19 among incarcerated people and staff. Our specific aims are to: (1) Identify ethical concerns and potential solutions for COVID-19 testing and vaccine strategies in correctional facilities using a community-engaged strategy; and (2) Characterize baseline COVID-19 incidence, disease progression and related-outcomes among incarcerated individuals and correctional staff. At the core of this work is a long-standing multidisciplinary team, including people with histories of incarceration, correctional policymakers, public health scientists, historians, legal scholars, and ethicists, which will identify ethical concerns and potential solutions to testing and vaccine implementation in correctional settings. We have partnered with the Florida, Rhode Island, and Minnesotastate departments of corrections and the Yakima County jail in Washington, to implement mass testing to characterize COVID-19 incidence, risk factors, and long-term outcomes in a diverse set of jails and prisons inrural and urban geographies. Together, the knowledge produced by this proposal will have a positive impact by providing feasible and ethical solutions for corrections to prevent COVID-19 morbidity and mortality through testing and vaccine distribution.",2020,2022,Yale University,3829777,Human Populations,Unspecified,Unspecified,Unspecified,Prisoners,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Research to inform ethical issues","Diagnostics | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease pathogenesis | Supportive care, processes of care and management | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making",2020 +C07233,2R01AI110700-06,"Cell entry, cross-species transmission and pathogenesis of novel coronavirus from Wuhan","The 21st century has recorded the emergence of three highly pathogenic respiratory coronaviruses, including Severe Acute Respiratory Coronavirus (SARS-CoV) in 2003, the ongoing Middle East Respiratory Coronavirus (MERS-CoV) in 2013 and a novel SARS-like coronaviruses SARS-CoV2 (SARS2) in Wuhan, China in Dec 2019. SARS2 causes COVID19, a severe acute respiratory distress syndrome (ARDS) and has infected 95000 individuals with ~20% severe cases and a ~3% mortality rate, resulting in over 3700 deaths. In the elderly, mortality rates approach 15%. The overall program goals are to identify the viral and host determinants, which regulate the atomic-level interactions between the SARS2 S-glycoprotein and various ACE2 receptor and associated entry components such as cellular proteases. The impact of these studies are high, as these interactions regulate 2019-nHCoV species specificity and host tropism, which play critical roles in viral pathogenesis and inform the evolutionary pathways leading to virus emergence and spread in humans and perhaps other intermediate hosts. In parallel, we apply these and other findings to developing robust mouse models of SARS2-mediated human disease, which is critical for not only evaluating viral pathogenesis but also for future testing of antiviral drugs, immunotherapeutics and vaccines.",2020,2025,University of North Carolina at Chapel Hill,766414,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2015 +C07234,3UL1TR002366-04S3,RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 Testing,"Project Abstract Local health departments are employing widely varying approaches to address the dramatic health inequities associated with the COVID-19 pandemic. Learning collaboratives have been effective in other settings for bringing entities together to support joint problem solving and reduce variance in approach. These collaboratives build upon shared experiences to help their members understand not only what to do but how to do it, providing knowledge and skills that are critical to successful implementation of interventions. This study aims to examine the effectiveness of a diverse, regional learning collaborative of health departments that will rapidly adapt, test, and implement community-driven solutions for COVID testing disparities using a pragmatic, hybrid type II trial design. Based on preliminary data from a community-led approach developed in a severely affected Kansas county (Wyandotte), the project will build Local Heath Equity Action Teams in 10 counties (4 urban and 6 rural) disproportionately affected by COVID and provide them with the training and resources needed to achieve COVID testing equity. These Local Health Equity Action Teams will come together into a multi-jurisdictional learning collaborative or `Community Partner Program' (Aim 1) that can share best practices and collaborate on developing, testing and evaluating multi-component intervention packages for addressing COVID. Initial supported interventions will include: community-sponsored pop-up testing events; home-based and worksite testing; community-informed communication strategies; and `support packages' for at-risk individuals and families receiving testing. Additional interventions developed or proposed by our local community partners or identified through national RADx-UP efforts will be continuously considered by the collaborative. Working with the local Action teams, we will conduct a series of semi-structured interviews and surveys within each local community (Aim 2) to better understand common and subgroup (racial, ethnic,geographic, etc.) barriers to and facilitators of testing. We will leverage existing epidemiologic surveillance tools to develop and track a series of county-level metrics of COVID testing inequities. Guided by the RE-AIM framework and the Consolidated Framework for Intervention Research, we will examine the effectiveness (Aim3) of the collaborative in improving uptake of COVID testing in vulnerable communities and examine the reach, adoption, implementation and maintenance of intervention components within each local community. This study will not only advance our understanding of how to achieve COVID testing equity but will also provide a framework for supporting underserved communities as they respond to future public health emergencies and COVID vaccination challenges.",2020,2022,University Of Kansas Medical Center,3755728,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication",2017 +C07235,3R01DA043089-05S2,Identifying and Engaging Urban HIV infected and uninfected YSMSM in care,"Abstract: Current data suggest a disproportionate burden of COVID-19 illness and death among racial and ethnic minority groups.1,2 In multiple urban cities across the United States (U.S.) Black and Latinx persons are disproportionately impacted by COVID-19 illness and death.1,3-5 Disproportionate rates are likely the result of concomitant comorbidities, and adverse social determinants of health, including high rates of substance use (SU), mentalhealth, structural racism, high population density, inadequate housing, and poor access to healthy foods.6,7 The same social determinants of health that predispose communities to COVID-19 illness, contribute to high rates of HIV in Black and Latinx sexual and gender minority youth (aged 15-24 ) (SGMY). COVID-19 will likely worsen social and economic inequalities, which predispose Black and Latinx SGMY to SU and to HIV.Exacerbated inequalities will also like result in further disruption of the HIV prevention and treatment cascades.8 The national strategy, Ending the HIV Epidemic (EHE), seeks to diagnose, treat and prevent onward infection in communities hardest hit by HIV, particularly Black and Latinx SGMY. High rates of substance use12 in BLSGMY has been identified as a key factor in treatment and prevention non-engagement, 13-15 and increased substanceuse may occur during the COVID-19 pandemic as a coping mechanism. SARS-CoV-2, which causes COVID-19, preferentially attacks the lungs, making YBLSGMY who smoke tobacco or marijuana, particularly at-risk.16-19 We will use a sequential explanatory mixed methods design, inclusive of cross-sectional surveys among 200 PUSH participants (both assigned male and female participants) (aim 1) and qualitative data of 48 participants and their service providers (aims 2-3), to understand potential ways in which the COVID-19 epidemic has affected personal life circumstances, risk behaviors, and health seeking behaviors; community barriers to COVID-19 prevention and treatment; and coping mechanisms to address psychosocial distressed experienced during this time. Specific Aim 1: Using a cross-sectional survey among 200 Black and Latinx SGMY enrolled in PUSH to characterize the psychosocial (including school closures, job loss, mental health and SU) disruptions and access barriers to HIV prevention, treatment and substance treatment services due to COVID-19. Specific Aim 2:Qualitatively describe how psychosocial disruptions due to COVID-19 alters BLSGMY's access to HIV prevention, treatment and substance treatment services and the coping mechanisms used to address disruptions. Specific Aim 3: Identify potential community barriers to COVID-19 treatment and prevention among BLSGMYand their service providers and how such experiences of medical mistrust and misinformation impact experiences of social disruption in BLSGMY. Potential barriers will be explored using paired depth interviews of BLSGMY and their providers. This supplement allows the team to better understand how the COVID-19 pandemic contributes to limited access for HIV prevention, treatment and substance treatment services, andhow potential community barriers and assigned sex at birth modifies this relationship.",2020,2021,Johns Hopkins University,159411,Human Populations,Black | Other,Adolescent (13 years to 17 years),Urban Population/Setting,Sexual and gender minorities | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication | Indirect health impacts | Social impacts",2016 +C07236,3UL1TR001414-06S2,University of California Health Participation in the National COVID Cohort Collaborative (N3C),"PROJECT Summary: Through this supplement, we will orchestrate a collective effort across the five CTSA Hubs at the University ofCalifornia (UC) Health to contribute data to, and become a strategic partner of, the National COVID Cohort Collaborative (N3C). By combining the data resources and research informatics expertise at UC Davis, San Francisco, Los Angeles, Irvine, and San Diego, UC Health is uniquely positioned to provide high-quality clinical data of diverse patient populations across the State of California to help N3C fulfill its mission to ""build a centralized national data resource that the research community can use to study COVID-19 and identify potential treatments as the pandemic continues to evolve."" The proposed work will leverage an existing UC-wide initiative on curating the UC COVID Research Data Set (UC CORDS), a continuously updated HIPAA Limited Data Set that contains comprehensive clinical information of all patients tested for COVID-19 at any UC Health facility. To ensure high-quality and timely data delivery, we will create a UC-wide governance structure to establish a master Data Transfer and Use Agreement (DTUA) with NCATS on behalf of all five UCCTSA Hubs, in addition to coordinating research ethics reviews. We will also create an informatics task force involving key stakeholders at each UC CTSA Hub to coordinate site-level data work. Data aggregation, quality assurance, and submission will be performed by the UC Health Data Warehouse (UCHDW) team at the Centerfor Data-Driven Insights and Innovation (CDI2) in the UC Office of the President.Glossary ACT Accrual to Clinical TrialsCDI2 Data-Driven Insights and Innovation CDW Clinical Data WarehouseCMBI Center for Biomedical InformaticsCOVID-19 Coronavirus Disease 2019 (COVID-19)CTSA Clinical and Translational Science AwardsDTUA Data Transfer and Use AgreementEHR Electronic health recordsi2b2 Informatics for Integrating Biology and the BedsideN3C National COVID Cohort CollaborativeOMOP Observational Medical Outcomes PartnershipPCORnet National Patient-Centered Clinical ResearchNetworkSHRINE Shared Health Research Information NetworkUC BRAID University of California Biomedical ResearchAcceleration, Integration, and DevelopmentUC CORDS University of California COVID ResearchData SetUC Davis CTSC University of California, Davis Clinicaland Translational Science CenterUC Irvine ICTS University of California, Irvine Institute forClinical and Translational ScienceUC ReX University of California Research ExchangeUCHDW University of California Health Data WarehouseUCLA CTSI University of California, Los Angeles Clinicaland Translational Science InstituteUCSD ACTRI University of California, San Diego AltmanClinical and Translational Research InstituteUCSF CTSI University of California, San FranciscoClinical and Translational Science Institute",2020,2024,University Of California-Irvine,498289,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2015 +C07237,3R01ES026994-05S1,"COVID-19 Pandemic among low-income Latino families in an agricultural community: Financial, occupational, and mental and physical health sequelae","ABSTRACT We have been engaged in the CHAMACOS study (R01ES026994, PI-Eskenazi), a longitudinal cohort study ofmore than 600 Latino primarily farmworker families (N=600 mother-child dyads, N=1200) in the agricultural Salinas Valley California for 20+ years. The overaching aim of this study has been to investigate the health sequelae of pesticide exposure over the lifecourse from in utero to adulthood. In this proposal, we aim to study the impact of the COVID-19 pandemic on these families. Low-income families, and particularly farmworker families, will likely be disproportionately infected by COVID-19 given cramped living quarters, their ""essential""work status, traveling to work in crowded farmworker buses, and close working conditions on packing lines. In addition, substantial epidemiologic and toxicologic evidence suggests that pesticides, including organophosphates (OPs), organochlorines (OCs), carbamates, pyrethroids, the herbicide glyphosate, and ethylenebisdithiocarbamate (EBDC) fungicides can impact immunologic suppression and increase susceptibility to infectious diseases and more severe disease. For these reasons, we estimate that between 20%-40% of the CHAMACOS cohort will have been infected by January 2021. In addition, we hypothesize that the CHAMACOS cohort will be more impacted by the pandemic given poverty, insecure employment, risk for food scarcity, immigration status, and poor access to health services. For the 600 mother-child dyads, we have collected key information prior to the pandemic on health, financial and food security, and other relevant variables that may have been altered by the pandemic or increased risk of infection. The specific aims of this proposed supplement are to collect data post-COVID-19 to assess change in health (weight gain, increase in blood pressure, increase in anxiety or depression), food and housing security, access to medical care for COVID-19 or non-COVID-19 related conditions, fear of immigration authorities, barriers to protective behaviors during the pandemic (crowded housing, no indoor running water, workplace policies), and SARS-CoV-2 infection by serology. We will assess whether cumulative pesticide exposure increased risk for infection and disease. Pesticide exposure will be determined in two ways: by using California's unique Pesticide Use Reporting data linked to 20-year residentialhistory (the lifetime of the child) and using existing biomarkers of exposure (including prenatal and early lifeexposure of the child). To our knowledge, there is no other study of a similar population given the hard-to-reach nature of this cohort, the richness of the existing data, and our long-term relationship with the families and the community. Thus, our proposal will give a rare window into a population at high-risk of contracting COVID-19 and our unique opportunity to understand how the pandemic affects low-income Latino families who are living and working in a farmworker community is unsurpassed.",2020,2021,University Of California-Berkeley,161528,Human Populations,Other,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Rural Population/Setting,Women | Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease transmission dynamics | Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences | Approaches to public health interventions | Community engagement",2016 +C07238,1R01AI157253-01,Genetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative Cross,"Abstract:The 2019 nCoV (SARS-CoV2 or nCoV2) is currently causing a global pandemic, and is on track to cause millions of infections, hundreds of thousands of deaths, and significantly disrupt healthcare systems and economies globally. nCoV2 is a group 2B coronavirus that is 75% identical to Severe Acute Respiratory SyndromeCoronavirus (SARS-CoV), which emerged in 2003. Approximately 10% of nCoV2 infections result in COVID-19 pneumonia that progresses to acute respiratory distress syndrome (ARDS), while a significant fraction of other individuals are asymptomatic or develop mild disease. While age, gender, and underlying health conditions predispose individuals to severe disease/death, we have a poor understanding of the factors that drive disease outcome. This knowledge is essential for understanding the pathogenesis of COVID-19, and for developing and testing safe and effective nCoV vaccines and therapies. However, while patient studies can provide insights into the disease risk factors, mechanistic analysis of these factors will require robust animal models of COVID-19 disease. Unfortunately, nCoV does not replicate in standard laboratory mice, and asignificant need exists for new animal models that reproduce human-like COVID-19 disease, including ARDS. Collaborative Cross (CC) mice vary significantly in their response to SARS-CoV, and we were able to take advantage of this variation both to develop new models SARS-CoV-induced disease, while also identifying host genetic factors that regulate disease outcome. Based on this experience, we propose take advantage of a new mouse adapted SARS-CoV2 virus (maCoV2), which was recently developed in the Baric laboratory, to screen apanel of CC mouse strains for susceptibility to maCoV2-induced disease. This work will accomplish two critical research objectives by: 1) developing critically needed mouse models of nCoV2-induced disease, and 2) identifying polymorphic host genes/pathways that regulate resistance or susceptibility to nCoV2-disease.",2020,2025,University of North Carolina at Chapel Hill,748384,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease models | Prognostic factors for disease severity",2020 +C07239,3R33ES024719-05S1,Low-Cost Versatile Sampler for Personal PM Exposure by Microenvironment,"Summary: Stemming the spread of the SARS-CoV-2 pandemic is a leading public health priority. The relative importanceof various transmission modes (e.g., surface contact, large droplet impact, small droplet aerosol), however, remains uncertain. This uncertainty hinders the prioritization of controls and undermines the validity of current guidelines (e.g., the 6-ft social distancing rule). Therefore, research is needed to elucidate whether large droplet or fine-mode aerosol inhalation are viable modes of disease transmittance. A major limitation of the extant research is that aerosol samples have not been collected within the breathing zone of individuals(whether they are infected or not); this limitation stems from the cost and physical burden posed by existing personal (wearable) air sampling technologies. We propose to adapt technologies developed under ourexisting grant (R33ES024719 Low-Cost, Versatile Sampler for Personal PM Exposure) for the detection of aerosolized SARS-CoV-2 RNA within the human breathing zone. We propose to collect the following types of real-world air samples from active healthcare facilities in Colorado: 1) patient breathing zone (symptomatic and asymptomatic), 2) room area (surface and air), and 3) healthcare worker breathing zone. We also propose to quantify viral RNA levels using a novel low-cost microfluidic assay. We hypothesize that enhanced bioshedding of SARS-CoV-2 aerosol will occur in the breathing zone of infected individuals (relative to matched samples collected at a 6-ft distance). Further, we will test this hypothesis for both droplet (up to 100 µm) and lung-penetrating (< 10 µm) aerosol by segregating collected samples by particle size. The information gained from this research will inform stakeholders about the relative importance of personal protective equipment, personal distancing, and local ventilation controls.",2020,2021,Colorado State University,431880,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Pathogen morphology, shedding & natural history | Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2020 +C07240,3U54GM104938-08S1,Oklahoma Shared Clinical and Translational Resources,"The pandemic caused by the novel coronavirus SARS-CoV-2 has resulted in substantial global morbidity and mortality including in Oklahoma and caused unprecedented interruptions in nearly all aspects of our lives.COVID-19 has demonstrated considerable disparities based on age and certain chronic illnesses as well asother social determinants of health. The population of the state of Oklahoma is at particular risk to SARS-CoV-2 due to its large rural population, strained healthcare system, and poor overall health. Rural populations in general are medically underserved, older, and experience significant health disparities that overlap with those comorbid conditions that can result in severe cases or even death from the infection. The Oklahoma Shared Clinical and Translational Resources (OSCTR) and its long-standing community-engaged research programs and partnerships are perfectly positioned to contribute to the knowledge base necessary to improve the effectiveness of interventions to increase testing in underserved and vulnerable populations. We have designed an approach that allows us not only to collect essential information about community, provider, and patient-relevant impediments to SARS-CoV-2 diagnostic testing but also to meet the critical need to increase testing in our state as rapidly as possible. The Community-engaged Approaches to Testing in Community and Healthcare settings for Underserved Populations (CATCH-UP) program will involve both practice-based and community-based approaches to maximize the reach of the RADx-UP consortium, broaden the potential perspectives that could be captured, and compare the effectiveness of strategies. The interventions will be pragmatic to allow CATCH-UP to respond to changing attitudes, barriers, and environments as the pandemic progresses as well as expected technology developments to produce more effective viral testing that canprovide rapid results to patients. The practice-based intervention will utilize our existing research infrastructureto assist 50 small primary care practices to implement guidelines-based testing and patient education about COVID-19 and risk mitigation strategies. Our community-based approach is designed to rapidly respond to community testing needs by deploying mobile testing sites that will provide operational support to increase the efficiency and the existing capacity for state-wide testing by Oklahoma's public health authorities. Together, we estimate that the CATCH-UP program will result in at least 105,000 SARS-CoV-2 tests performed during the first year of implementation. A comprehensive, ongoing evaluation will be performed to analyze patient and provider attitudes, barriers and facilitators of viral testing, identified health disparities caused by COVID-19,effectiveness of the intervention in both settings, and to allow robust collaboration with other RADx-UP consortium sites.",2020,2023,University Of Oklahoma Hlth Sciences Ctr,3240887,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication",2020 +C07241,3P50DA048756-02S2,Prevention Research Center: Parenting Among Women Who Are Opioid Users,"PROJECT Summary: The global SARS-CoV-2 pandemic that causes the severe respiratory illness COVID-19 is the worst health crisis the United States has faced in a century. Although this highly contagious virus has infected millions of Americans already, the disease burdens are disproportionately born by historically underserved populations such as Latinx communities. Nationally, Latinx people with COVID-19 are hospitalized at four times the rate of Whites and have much higher rates of morbidity and mortality. This disparity is notable in Oregon, where the13% of our population that is Latinx represents approximately 44% of COVID-19 cases. An urgent need exists to reach Oregon's Latinx community with public health and prevention messages to increase testing. This project will implement a culturally-tailored community outreach and testing program to increase the reach, access, and uptake of testing in Latinx communities in Oregon. The project will bring together a world-class team of prevention scientists, public health experts, Latinx researchers, community partners, and biologists who have been working together to conduct SARS-CoV-2 diagnostic testing since March, soon after the pandemic first arrived in the U.S. This team has established a CLIA-certified laboratory and honed moleculartesting protocols, hired and trained laboratory personnel and a field research team, procured diagnostic testing equipment and supplies, and partnered with county public health offices and hospitals throughout the state to conduct testing. The team also conducted a comprehensive community assessment using community-based participatory methods to gather Latinx community feedback on modes of communication, health messages,and testing protocols, and staffed multiple county-led testing sites serving Latinx communities. Using these resources and expertise as a foundation, a Sequential Multiple Armed Randomized Trial (SMART) will enable the evaluation of strategies for increasing testing rates and promoting health behaviors in Latinx communities.Specifically, culturally informed, community-oriented interventions will determine tools and best practices to increase testing rates and health behaviors. The efficacy of different types of approaches for increasing access to and utilization of testing will be evaluated. Lastly, the work will examine a set of county-level variables thought to affect communities' abilities to sustain testing capacity. With support from a Latinx Community and Scientific Advisory Board, the project will ramp up to ultimately support 36 community testing sites across sixcounties in Oregon to serve Latinx communities. Over time, this project will help communities institutionalize optimal local testing frameworks supported by UO laboratory facilities for testing capacity, technical support fortesting logistics, and collection of data on health behaviors, testing rates, and sustainability. The resulting structures and systems will be poised for future scale-up to other vulnerable communities and/or for otherpublic health purposes (e.g., vaccination campaigns). If successful, this project will lead to a major reduction in COVID-19 health disparities in underserved populations.",2020,2022,University Of Oregon,4166575,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Pregnant women | Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Health Systems Research","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication | Health service delivery",2020 +C07242,3R34DA050254-01S2,Biological and Environmental Contributions to Healthy Baby Development in Diverse Population,"Project Summary: The COVID-19 pandemic represents the most significant environmental event in living history and is leading to unprecedented social, economic and health consequences. There is an urgent need to longitudinally study the impact of the pandemic on pregnant women and the care they receive, and to understand the consequences for their children's birth outcomes and neurobehavioral development. This project adds an eighth site to address these critical gaps by building upon ongoing harmonized research efforts across seven geographically-representative sites from the NIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, Oregon Health Sciences University, Washington University in St. Louis, University ofPittsburgh, Cedars Sinai Medical Center, University of Vermont and Northwestern University. We will enroll pregnant and postpartum women into a multi-wave study in which we assess medical, economic, psychosocial and substance use risk across pregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral development during the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 related stress leads to differences in birth outcomes, parenting stress and infant temperament and neurodevelopment and 2) substance use, mental health and economic risk enhance susceptibility to negative COVID-19 related health and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth and postpartum data will be obtained across a 3-month period in N=50 pregnant and new mothers at our site (providing a total consortium sample of N=750) to generate individual temporal profiles of COVID-19 related experiences and responses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic. Further, to identify avenues for intervention, we will evaluate substance use, poor mental health and low social economic status as risk factors and coping, agency and utilization of resources as resilience factors that influence COVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects of geographic location will be used to examine the influence of pandemic severity, variation in local government policies and resource availability on these outcomes. Finally,we will collect and bank longitudinal perinatal biospecimens in N=20 women at our site that will contribute to a foundation for future studies to evaluate the biological mechanisms through which the effects on maternal psychological and physical health influence offspring brain and behavioral development. Through this analysis of COVID-19 related stress, contextual factors and child outcomes, we will develop comprehensive understanding of effects and modifiers of this event on health outcomes in individuals that vary in dispositional risk during perinatal life, one of the most sensitive timepoints in human development.",2020,2021,Children's Hospital of Los Angeles,169134,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Economic impacts | Health service delivery,2019 +C07243,3R34DA050262-01S2,"1/5, HEAL Consortium: Establishing Innovative Approaches for the HEALthy Brain and Child Development Study","The COVID-19 pandemic has affected the mental and physical health of children and their parents. The pandemic has also affected the ability to conduct in-person research at most institutions across the United States. However, recent technological advances may allow many in-person assessments to transition to virtual formats. There is an urgent need to develop virtual versions of currently used assessments of the home environment and parent-child interactions, and to concurrently study the effect of the COVID-19 pandemic on family relationships. The proposed project seeks to address this urgent need by building upon ongoing research efforts among three sites from the NIH HEALthy Brains and Cognitive Development (HBCD) study:Arkansas Children's Research Institute, Cincinnati Children's Hospital, and the University of North Carolina at Chapel Hill. We will develop and test a virtual version of the HOME Inventory in 90 mothers with infants between 6-18 months of age. We will validate this virtual version by performing in-person HOME Inventory assessments in 45 of these dyads. In all participants, we will use standard questionnaires to assess COVID-19 exposure and impact. Finally, we will examine associations between regional and temporal variations in COVID-19 exposure and impact and dimensions of the HOME Inventory. The results of this study will be used to finalize the development of a virtual HOME Inventory protocol that can be widely used in future studies, including the HBCD Phase II study.",2020,2021,University of North Carolina at Chapel Hill,154946,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2019 +C07244,3R34DA050268-01S2,4/5 HEAL Consortium: Establishing Innovative Approaches for the HEALthy Brain and Child Development Study,"PROJECT SUMMARY/Abstract: The COVID-19 pandemic has affected the mental and physical health of children and their parents. The pandemic has also affected the ability to conduct in-person research at most institutions across the United States. However, recent technological advances may allow many in-person assessments to transition to virtualformats. There is an urgent need to develop virtual versions of currently used assessments of the home environment and parent-child interactions, and to concurrently study the effect of the COVID-19 pandemic on family relationships. The proposed project seeks to address this urgent need by building upon ongoing research efforts among three sites from the NIH HEALthy Brains and Cognitive Development (HBCD) study:Arkansas Children's Research Institute, Cincinnati Children's Hospital, and the University of North Carolina at Chapel Hill. We will develop and test a virtual version of the HOME Inventory in 90 mothers with infants between 6-18 months of age. We will validate this virtual version by performing in-person HOME Inventory assessments in 45 of these dyads. In all participants, we will use standard questionnaires to assess COVID-19exposure and impact. Finally, we will examine associations between regional and temporal variations inCOVID-19 exposure and impact and dimensions of the HOME Inventory. The results of this study will be usedto finalize the development of a virtual HOME Inventory protocol that can be widely used in future studies, including the HBCD Phase II study.",2020,2021,Cincinnati Childrens Hosp Med Ctr,169281,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2019 +C07245,3U01DA036939-06S1,Multilevel Influences on HIV and Substance Use in a YMSM Cohort,"Abstract: Critical and urgent COVID-19 research questions will be addressed by characterizing SARS-CoV-2 seroprevalence and symptom profile in a racially diverse cohort of substance-using YMSM at baseline and again 6 months later using a home-collected, quantitative assay for antibodies expected to neutralize SARS-CoV-2 infectivity in vitro. The following are the specific aims: (1) Characterize socio-behavioral risks of COVID-19 by testing hypotheses that: a. At time of wave 1 testing in summer 2020, SARS-CoV-2 seroprevalence and symptom rates will be higher among Black and Latinx than White participants. Subsequent seroconversion will also be greater among Black and Latinx substance-using YMSM RADAR participants. b. Substance use will be associated with increased seroprevalence and symptoms. Specifically, utilization of combustible or vaporized nicotine or cannabis products, as well as methamphetamine, will increase prevalence of SARS-CoV-2 infection. Use of these substances will also predict seroconversion over subsequent follow-up. c. Participants who report sharing of drug smoking/vaporizing paraphernalia since March 2020 will have an increased seroprevalence, over-and-above the effect of use alone, due to additional transmission risk from contact. Sharing paraphernalia at wave 1 will also predict seroconversion over subsequent follow-up. (2) Understand COVID-19 risks associated with systemic inflammation, HIV-associated factors, and declining anti-SARS-CoV-2 antibodies by testing hypotheses that: a. Systemic inflammation is associated with increased sero-prevalence/-conversion and symptoms. b. SARS-CoV-2 seroprevalence may differ between HIV-infected and HIV-uninfected participants, or with antiretroviral use as PrEP or treatment (ART), after controlling for systemic inflammation. c. Lower CD4 cell count (in people living with HIV) is associated with decreased anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG quantity and/or duration. d. Lower quantity and/or loss of detectable anti-SARS-CoV-2 spike RBD IgG is associated with higher risk of SARS-CoV-2 reinfection (a second, separate episode of PCR positivity in a subsequent peak of cases).",2020,2025,Northwestern University At Chicago,157325,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2014 +C07246,3R34DA050261-01S2,3/5 HEAL Consortium: Establishing Innovative Approaches for the HEALthy Brain and Child Development Study,"The COVID-19 pandemic has affected the mental and physical health of children and their parents. Thepandemic has also affected the ability to conduct in-person research at most institutions across the UnitedStates. However, recent technological advances may allow many in-person assessments to transition to virtualformats. There is an urgent need to develop virtual versions of currently used assessments of the homeenvironment and parent-child interactions, and to concurrently study the effect of the COVID-19 pandemic onfamily relationships. The proposed project seeks to address this urgent need by building upon ongoingresearch efforts among three sites from the NIH HEALthy Brains and Cognitive Development (HBCD) study:Arkansas Children's Research Institute, Cincinnati Children's Hospital, and the University of North Carolina atChapel Hill. We will develop and test a virtual version of the HOME Inventory in 90 caregivers with infantsbetween 6-18 months of age. We will validate this virtual version by performing in-person HOME Inventoryassessments in 45 of these dyads. In all participants, we will use a standard questionnaire to assess COVID-19 exposure and impact. Finally, we will examine associations between regional and temporal variations inCOVID-19 exposure and impact and dimensions of the HOME Inventory. The results of this study will be usedto finalize the development of a virtual HOME Inventory protocol that can be widely used in future studies,including the HBCD Phase II study.",2020,2021,Arkansas Children'S Hospital Res Inst,153047,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Social impacts,2019 +C07247,3R37DA015612-17S1,Making Better Decisions: Policy Modeling for AIDS and Drug Abuse,"Project Summary/Abstract: In 2019, our competitive renewal for our NIDA-funded work on opioids, HIV, and HCV was funded with a MERIT award. In this supplement to our MERIT grant, we will address pressing issues in vulnerable populations at risk from SARS-CoV-2. We will adapt the modeling frameworks we have developed to address how best to protect vulnerable populations from COVID-19, including people who inject drugs (PWID), people who are incarcerated, and people in other vulnerable settings, including long-term care facilities, and schools. We will address strategies to protect vulnerable populations, including physical distancing measures, scaled-up and targeted testing and tracing, and strategic deployment of new technological innovations in diagnostics, therapeutics and vaccines as they arise. Our aims are to: 1. Model the intersecting epidemics of SARS-CoV-2, HIV and HCV in opioid-using and related vulnerable populations. We will extend our foundational epidemic models of HIV and HCV to include SARS-CoV-2. Doing so enables us to analyze the impacts of strategies in Aims 2 and 3. 2. Model the epidemiologic and population health impacts of currently available strategies to preventand mitigate the harms from transmission of SARS-CoV-2 in vulnerable populations. We will evaluate prevention strategies involving physical distancing and intensive testing programs for vulnerable populations.We will assess the impact of strategies on epidemiologic outcomes including incidence, prevalence, mortality, life expectancy, quality of life, and quality-adjusted life years (QALYs). 3. Model the epidemiologic and population health impacts of future strategies, including improved therapeutics and vaccines, to prevent and mitigate the harms from transmission of SARS-CoV-2 inpopulations of interest. Because no single and sustainable strategy based on currently availabletechnologies will likely have sufficient impact on reducing risks of continuing SARS-CoV-2 transmission, we will examine selected key strategies based on technologies that may become available in the next 18 months, particularly the use of a partially effective vaccine. The proposed work will synergistically expand on our current project and provide clinicians and policy makerswith critically needed guidance about which strategies can most efficiently mitigate the national public healthcrisis from COVID-19 in vulnerable populations and settings.",2020,2023,Stanford University,380547,Other,Unspecified,Unspecified,Unspecified,Drug users | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities,2002 +C07248,3UL1TR003017-02S2,New Jersey Alliance for Clinical and Translational Science: NJ ACTS,"Summary: The COVID-19 pandemic disproportionately impacts members of under-represented minority (URM) communi-ties. Unfortunately, URM and other vulnerable communities remain profoundly under-tested. As such, new ap-proaches are needed to disseminate and accomplish testing that could be generalized across the US. New Jersey can serve as a unique, virtual testing laboratory, ranking 11th in the US in population, 2nd in the US (after NY) in the per capita rate of COVID-19 deaths, and 5th in total cases and represents a highly diverse state with substantial Black and Latinx minority populations. At Rutgers, we have assembled cohorts of healthcare workers (HCWs) to monitor the spread of COVID-19 and to enroll subjects for clinical and vaccine trials. While building our cohorts,we recognized many URMs serve as HCWs or personal care aides often in lower-income roles. Further, we also found these workers were more often infected compared with those with higher income occupations. Given these observations, we posit that HCWs in occupations at lower incomes would facilitate testing among their house-holds and their communities. In a sense, these HCWs can serve as ambassadors to catalyze community-based COVID-19 testing. NJ HEROES TOO (New Jersey Healthcare Essential WoRker Outreach and Education Study- Testing Overlooked Occupations) proposes to approach URM HCWs who we have identified as index individu-als who will act as ambassadors to help expand testing in their households and extended networks. In Aim 1, we will co-design, develop and implement an innovative, HCW-centric outreach intervention strategy to engage Black and Latinx minority communities. We will explore community perceptions about COVID-19 testing, treatment, and vaccination to design COVID-19 testing materials and messages that are culturally tailored to address concernsof Black and Latinx minority communities. In Aim 2, we will conduct a mixed methods study to evaluate the effectiveness and cost of: (1) the HCW-focused outreach intervention strategy versus (2) standard community engaged outreach, working with community based organizations (CBOs). We will explore contextual factors (individual, family, and community) affecting COVID-19 testing implementation outcomes and scalability. The primary out-come will be uptake of COVID-19 testing in the targeted populations. We propose testing with the novel Rutgers Clinical Genomics Laboratory/RUCDR saliva test, the first FDA-authorized diagnostic test using saliva to detectSARS-CoV-2 for non-invasive, home based self-testing. We hypothesize that a participatory outreach strategy approach focused on identified index HCWs will mobilize quicker uptake of testing within community settings than best-practice CBO recruitment approaches. We also hypothesize that recruitment through index HCWs will be more successful for hard to reach participants compared to a traditional CBO approach. The strategy focusing on HCWs could easily be expanded to other front-line and essential workers, making the strategy generalizable and sustainable.",2020,2024,Rutgers The State University of New Jersey,3792941,Human Populations,Black | Other,Unspecified,Unspecified,Vulnerable populations unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2020 +C07249,3U54MD012393-04S3,FIU Center for Reducing Health Disparities in Substance Abuse & HIV in South Florida (1),"SUMMARY Background: The United States (US) remains one of the epicenters of the global COVID-19 public health emergency, resulting in the government's implementation of mitigation policies to stem and contain the virus.Despite these measures, people of color (POC - Blacks, Latinx and American Indian/Alaska Native populations) in the US are disproportionately represented in the epidemic. Objectives: The overall objective of this study is to evaluate the impact of macro and ecological policies by (a) using state and county level data to report on COVID-19 health outcomes experienced by communities of color and (b) conducting in-depth interviews among community members and providers to understand their perceptions about accessing and providing healthcare services. Design: Firstly, there will be an ecological study at the US state and county levels examining the relationship between racial/ethnic density and COVID-19 outcomes, considering selected COVID-19 risk factors (crowding, poverty level, percentage of essential workers) as moderators in that relationship. Secondly, there will be a policy study of differences on timing, interpretation and implementationof federal and state level mitigation policies on COVID-19 outcomes. Finally, interviews will be conducted to understand provider and patient viewpoints about how macro level social and health policies implemented by federal and local governments influence providers' perception about delivery of care and community members'perception about accessing COVID-19 healthcare services. Analysis: Descriptive statistics will be used to describe COVID-19 prevalence by racial/ethnic density in states and counties, followed by bivariate correlations. Any statistically significant correlation (<0.10) in the bivariate correlations will be incorporated intothe regression models with COVID-19 incidence, prevalence and death rate as outcomes. Regression models will be used to determine the relationship between COVID-19 outcomes and state and county level demographic data and COVID-19 policy data. For the interviews, content analysis will be used to analyze qualitative data about perceived barriers and facilitators accessing and providing care. Significance: The results of this study will help to understand the underpinnings of social mechanisms and disparities contributingto the overrepresentation of underrepresented minority populations in the COVID-19 public health crisis. The study objectives are in line with recent NIMHD priorities issued for the COVID-19 response to support studies that investigate the ""influence of state and local mitigation policies on differences in health services utilization and health outcomes, the role of community-level protective factors and interventions in mitigating the adverse consequences of the sector disruptions caused by the outbreak, the influence of COVID-19-related racism andother types of discrimination, and the role of social determinants of health in influencing preventive health behaviors"".",2020,2022,Florida International University,195567,Human Populations,Black | Other,Adults (18 and older) | Unspecified,Unspecified,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2017 +C07250,3U54MD007595-12S5,Enhancing Louisiana Health Professionals in Communication Methods/Strategies to Increase COVID 19 Vaccination Rates of Residents of Vulnerable Communities (LaHealthCom),"Project Summary/Abstract Educating Louisiana Health Professionals in communication methods/strategies to increase COVID 19 vaccination rates of residents of vulnerable communities (LaHealthCom) Introduction LA ranks first in the US for COVID-19 cases by population with a case rate of 2,960 per 100,000and is fifth in deaths by population with a death rate of 97 per 100,000. Furthermore, there areespecially disturbing demographic trends in LA with Blacks representing the highest percentage of cases (40.2%) and second highest percentage of deaths (48.7%). Vaccines for prevention ofCOVID-19 are in development with 29 candidate vaccines in clinical evaluation, of which 6 are in Phase 3. To reduce COVID-19-related morbidity and mortality, an approved vaccine must be disseminated with rapid uptake in the community. Mistrust of the health care system and mistrust of experimentation create barriers to rapid and wide- spread acceptance of novel COVID-19 preventive and therapeutic interventions among vulnerable groups. Surprisingly, many minority health care workers who are not now living in vulnerable communities are also reluctant to get vaccinations and/or to give vaccinations. Our College of Pharmacy have experienced this regularly among the health care staff with whom they work in vulnerable community clinics, communitypharmacies and churches. This reluctance also occurs among a noteworthy percentage of Xavier's pharmacy students. Louisiana's Base COVID 19 vaccination grant, ""Louisiana Community-Engagement Research Alliance against COVID-19 in Disproportionately Affected Communities"" (La-CEAL - attached) will achieve understanding of the perceptions of the residents of vulnerable communities about COVID-19 vaccination in order to develop effective media and communication strategies focused on the residents of these communities that will increase their knowledge of, and address barriers to, participation in the vaccination process as well as clinical trials. To fully implement this strategy will take between 6 and 9 months. However, a variety of healthprofessionals are already meeting with these residents and, to the extent they can be encouraged to become vaccinated and learn how to effectively encourage residents of vulnerable communities to become vaccinated, will have an even more immediate impact that will be sustainable over time. As such, this proposal will first, identify barriers to COVID 19 vaccination faced by health care providers and successful educational strategies that could be used to help them overcome these barriers and communicate to vulnerable communities in a manner that encourages residents to be vaccinated. Second, with a focus on health care staff working in churches, Federally Qualified Health Clinics and Community Pharmacies invulnerable areas as well as Xavier's College of Pharmacy and Physician Assistant programfaculty and students who staff these organizations, this data will be used to create innovative educational strategies to address the attitudes of health care professionals towards COVID 19 vaccination as well as help them develop communication and messaging capabilities to be used on the residents of vulnerable communities they serve. Resultant educational approaches will be implemented and tested in these same churches, Federally Qualified Health Clinics and Community Pharmacies in vulnerable areas as well as Xavier's College of Pharmacy and Physician Assistant program, evaluated and revised. Finally, best practices will be implemented at Xavier and disseminated to the vulnerable community organizations in which they serve as well as to other health provider educational institutions such as Colleges of medicine, nursing and pharmacy and their professional continuing education associations.",2020,2023,Xavier University Of Louisiana,200000,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication,2009 +C07251,3R01DA027379-08S1,"DAT 18-06 Feasibility and Acceptability of HIV, HCV, and Opioid Use Disorder Services in Syringe Service Programs","PROJECT SUMMARY COVID-19 threatens to exacerbate the national opioid crisis by reducing availability and access to harmreduction and health services delivered by syringe service programs (SSPs). Monitoring the impact of COVID-19 on the availability and delivery of harm reduction and health services by SSPs in the U.S. over time is imperative for guiding local and national opioid policies. Failure to restore services will require additional responses to avoid adverse consequences, including HIV and hepatitis C outbreaks, whereas potentially beneficial responses, such as eliminating 1:1 syringe exchange requirements, should be disseminated widely. This supplement proposes collecting and analyzing longitudinal data on the impact of recovery from COVID-19 on SSPs. We will describe the changes in national SSP services in response to COVID-19 over one year via qualitative interviews and short surveys with SSPs every 6 months. Interviews will explore changes in harmreduction and health services offered; funding, adoption and sustainment of innovative services and servicedelivery; and barriers and facilitators for SSPs to delivering different services over a year. Descriptive data analysis will be conducted to determine if programs recover, maintain, or adapt services 6 and 12 months afterthe baseline survey. Qualitative data will be analyzed using content analysis. We will also conduct alongitudinal analysis to determine the associations between COVID-19 reported infections, COVID-19response policies, and SSP services delivered. SSPs registered with the North American Syringe ExchangeNetwork will be invited to participate in the longitudinal study that will collect monthly data on 1) number ofsyringes dispensed, 2) number of naloxone kits dispensed, 3) estimated number of participants served (directlyand through secondary exchange), and 4) whether the SSP offered any on-site HIV or HCV testing in thatmonth. COVID-19 reported infections and policies will be derived from publicly available data sources. We will conduct interrupted time series analysis to determine if changes in local COVID-19 stay-at-home policies areassociated with changes in the monthly number of syringes and naloxone distributed and per client rates,taking into account reported local infection rates. Time-to-event analysis will be used to assess the impact ofCOVID-19 infection rates and policies on HIV and HCV testing. Results will be disseminated to national andlocal policy makers to support decision making for harm reduction and health services provided to people who inject drugs.",2020,2022,Weill Cornell Medicine - Cornell University,179194,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2009 +C07252,3U54MD012393-04S4,FIU Center for Reducing Health Disparities in Substance Abuse & HIV in South Florida (2),"COVID-19 is a pandemic that has caused disastrous and unprecedented public health and economicconsequences in the United States. The pandemic has seriously and negatively affected Americans' physical and mental health, and disproportionately so the health of Americans from underrepresented minority backgrounds (URM). The proposed supplemental project will engage the large network of FIU-RCMIcommunity partner organizations forged by our Engagement Core. Our primary focus will be on Miami-Dad eorganizations serving URM communities suffering disparities in rates of COVID-19 fatalities, infection,exposure, testing, and access to care. Our primary emphasis will be the developing, designing, and mounting of community-partnered efforts (i.e., Town Hall Meetings) to promote COVID-19 vaccine literacy among URM groups, with direct attention to readiness for participation in (a) candidate vaccine trials and (b) approved vaccine rapid deployment. The aims of this proposed supplement are to inform and educate Miami-Dade URMcommunities through Town Halls facilitated by community organizations that serve these hard-to reach communities. Our efforts will be community partnered and involve a formative phase for developing and testing materials, and an implementation phase for conducting Town Halls. The implementation phase also will include assessing the Town Halls' impact on readiness for participation in (a) candidate vaccine trials and (b) approved vaccine rapid deployment. We anticipate reaching a minimum of 700 community stakeholders andinfluencers through the Town Halls. Town Hall participant data will be collected through real-time polling at theopening (pre) and close (post) of each Town Hall meeting. We hypothesize Town Hall participants will demonstrate pre-to-post increases in: knowledge of the risks and benefits of COVID-19 vaccine trials and vaccines; knowledge of the scientific process and vaccine safety and efficacy; confidence about participating in vaccine trials; trust in receiving the approved vaccines; and readiness to participate in vaccine trials and approved vaccines. Separately, Town Hall participants will be asked if they would like to participate in a vaccine trial; any Town Hall participant indicating interest will be asked to provide contact information, and will receive a follow-up contact from the FIU-RCMI with information and instructions on vaccine trial participation.1",2020,2022,Florida International University,199998,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2017 +C07253,1U24MD016258-01,RADx-UP CDCC,"Abstract: There is an urgent need to reduce disparities in COVID-19 associated morbidity and mortality outcomes in historically marginalized and vulnerable populations disproportionately affected by the COVID-19 pandemic. To address this need the Rapid Acceleration of Diagnostics for Underserved Populations (RADx-UP) program willsupport Community-Engaged Testing Research Projects and Social, Ethical and Behavioral Implications (SEBI) Research Projects to understand SARS-CoV-2 infection patterns and increase access and effectiveness of diagnostic methods in underserved and/or vulnerable populations. The Duke Clinical ResearchInstitute (DCRI), the UNC Center for Health Equity Research (CHER), and Community-Campus Partnershipsfor Health (CCPH) propose to serve as the Coordination and Data Collection Center (CDCC) to provide management, direction, and overall coordination of the RADx-UP consortium. Together, our multidisciplinary experience in project coordination; COVID-19 thought leadership; regulatory science; community engagement;health equity research; social justice; adult and child research; statistics; data science; and clinical researchinformatics will advance the objectives of the projects in the RADx-UP Program. Our overarching goal is to implement a community-centered approach and establish an effective, flexible, participatory, and sustainable CDCC that will serve as the infrastructure to maximize the community impact of projects in the RADx-UPProgram. To achieve this vision, we will establish a program framework comprised of four cores. Our Administration and Coordination Core, in collaboration with NIH scientific staff, will facilitate the work of theRADx-UP Program in overarching administrative management. The COVID-19 Testing Core will advise andguide COVID-19 testing protocols; curate emergent testing data; and administer the Rapid Pilot StudiesProgram. The Community and Health System Engagement Core will support a community of practice across the RADx-UP Program; provide support in exchanging best practices across communities on recruitment,engagement, and retention of study participants; and coordinate the dissemination of study findings from RADx-UP projects. The Data Science and Biostatistics Core will manage data collection, integration, andsharing for the RADx-UP Program including merging and harmonization of multiple and diverse data sourcesand provide data standards, data collection design, and biostatistics consulting services. The RADx-UP CDCCgoals will be met using established infrastructure and subject matter experts and will be customized to meetthe variable needs of the RADx-UP community. Using the highest research standards, our team will accomplish the goals set out by the NIH in managing this critically important collaborative effort.",2020,2024,Duke University,20162334,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Diagnostics | Disease transmission dynamics | Community engagement | Communication,2020 +C07254,MR/N026993/1,Pathfinder:Experimental Human Challenge with Genetically Modified Commensals to Investigate Respiratory Tract Mucosal Immunity and Colonisation,"This is a pathfinder study to establish the utility of experimental human challenge with a genetically modified commensal bacterium as a future method to investigate pathogenesis, immunity and to discover and test new vaccines. The commensal bacterium Neisseria lactamica (Nlac) does not have a polysaccharide capsule , so any adaptive immune response to this bacterium after colonisation of the nasopharynx must be directed at non-capsular antigens, providing a good platform for assessing non-anti-polysaccharide immunity against colonising bacteria in the upper respiratory tract. A wild-type strain of Nlac Y92-1009 (Nlac), will be chromosomally modified to express the strongly immunogenic meningococcal antigen PorA (GM-Nlac). GM-Nlac will be fully characterised, in particular with respect to enhanced antimicrobial or serum resistance, and altered genome stability cf Nlac. An application will then be made to DEFRA and the National Research Ethics Service to perform a controlled infection study in which non-smoking male participants aged 18-45 will be infected intranasally at a dose of 10,000 colony forming units (selected because we previously have infected >350 volunteers with Nlac at this dose) and then permitted to re-enter the community after challenge and followed up for 4 weeks. In a comprehensive serological and cellular immunological study we will define the nature and kinetics of the PorA-specific immune response to colonising GM-Nlac and measure recombination in carried isolates over the ensuing period of carriage. PorA is phase variable so we will determine the effect of phase variation in a second challenge experiment by comparing the serological and cellular responses to GM-Nlac expressing PorA under a phase variable promoter with one that is constitutively highly expressed. We will also compare the immune response to Nlac antigens between GM-Nlac and Nlac infected participants, to understand the effect of immunodominant antigens on immunity.",2020,2020,University of Southampton,118454.4,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2017 +C07255,C19-IUC-384,Evidenced based mental health and wellbeing resources made by young people for young people in the COVID-19 context,"Young people have faced extensive disruption and challenge throughout the COVID-19 pandemic. There is good evidence to draw on to provide advice and support, but this is often not easily available to young people in accessible and engaging forms. This is an MRC/AHRC/ESRC Adolescence, Mental Health and the Developing Mind Rapid Knowledge Mobilisation Project led by UKRI Emerging Minds and Triumph Networks, and supported by the wider Mental Health Networks.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C07256,C19-IUC-383,AGILE Clinical Trial Platform,"The AGILE clinical trial platform has been launched specifically to test new COVID-19 treatments, faster than ever before. AGILE is an adaptive randomized seamless Phase I/II trial platform that seeks to quickly establish a safe range of doses and investigates treatments for potential efficacy using a Bayesian sequential trial design.",2020,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial, +C07257,C19-IUC-382,How has COVID-19 and associated mitigation measures impacted on the mental health of carers?,"There are an estimated nine million carers in the UK and pre-pandemic studies indicate that carers have poorer mental health than the general population. With many formal and informal carer support schemes withdrawn due to Covid restrictions we seek to understand how carer mental health may have been affected by the pandemic. Using survey data (Understanding Society and COVID-specific surveys) we will explore changes in mental health of those caring for others in the home. We will consider the relationship of carer to care-recipient and the nature of the recipient's condition, as well as the impact of factors such as the withdrawal of external support, changes to carer workload and role, and the shielding status of both carer and care-recipient.",2020,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C07258,C19-IUC-381,Mobility patterns as potential proxy for contact models,This project focuses on mobility patterns including the extent to which people move outside of their residence as a proxy for contact patterns. This measure feeds into other workstreams to further understand the COVID-19 pandemic.,2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C07259,C19-IUC-380,Vaccines allocation and trial design,This project focuses on vaccine trial design and optimal allocation of vaccines​. Global support and linked to Impact and modelling project.,2020,-99,MRC Centre for Global Infectious Disease Analysis,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine design and administration, +C07260,C19-IUC-379,Phylodynamics,"This project focuses on phylodynamic analysis of SARS-CoV-2. Phylodynamic analysis include epidemiological, immunological and evolutionary processes.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C07261,C19-IUC-378,Global Impact and LMICs,"This project focuses on the COVID-19 trajectory in LMICs, and on individual country support.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,, +C07262,C19-IUC-377,Real-time modelling of epidemic trajectories,"This project focuses on the epidemic trajectories of COVID-19 (UK focus). This includes understanding of carehome, hospital and community transmission and considerations for the winter season. In addition, this workstream provides scientific support to Scientific Pandemic Influenza Group on Modelling (SPI-M) and the Scientific Advisory Group for Emergencies (SAGE).",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C07263,C19-IUC-376,Impact and economic modelling of Covid-19 including resource allocation,"This project focuses on what the direct and indirect economic impact of COVID-19 is. This includes the allocation of resources such as vaccines and therapeutics, both within and between countries.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts, +C07264,C19-IUC-375,Outbreak cluster detection and response,"This project focuses on detecting small, localised flare ups of cases. This includes location specific analysis and incoroprates test and trace and other data.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C07265,C19-IUC-374,Severity of COVID-19,"This project focuses on quantifying the burden of COVID-19. This includes estimates of the case fatality and infection fatality ratio, understanding disease progression and key epidemiological delays, co-morbidities as risk factors for severe outcomes, and quantifying excess deaths during the pandemic.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping, +C07266,C19-IUC-373,Developing novel methods and data sources for outbreak analysis,"This project focuses on the COVID-19 trajectory in LMICs, and on individual country support.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening, +C07267,C19-IUC-372,Transmission dynamics and control of Covid-19,"This project focuses on where transmission of SARS-CoV-2 occurs and what the implications are for control of the epidemic. The project explores how the pandemic has evolved over the first wave, the extent to which mobility patterns can be used as a proxy for transmission, and the non-pharmaceutical interventions employed by different countries. As more evidence emerges that transmission is occuring in specific high-risk settings, this project aims to characterise these risk factors for transmission.",2020,-99,MRC Centre for Global Infectious Disease Analysis,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities, +C07269,C19-IUC-370,Clonal haematopoiesis and Covid-19 disease severity,"Professor George Vassiliou's lab are investigating the hypothesis that clonal haematopoiesis may be linked to increased severity of Covid-19, if proven this would transform disease understanding, help identify at-risk individuals and support immediate initiation of relevant therapeutic approaches. The team have received a European Hematology Association COVID-19 in Hematology Research Grant for their project.",2020,-99,Wellcome - Medical Research Council Cambridge Stem Cell Institute,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C07270,C19-IUC-576,International COVID-19 Data Research Alliance and Workbench,"The International COVID-19 Data Research Alliance and Workbench provide a co-ordinated international platform to enable researchers to access global data to derive rapid insights about COVID-19 and speed up the development of treatments. Convened by Health Data Research UK, the Alliance is an independent consortium of leading life science, philanthropic and research organisations uniting to respond to the COVID-19 global pandemic. The first intiative for the alliance, The Workbench, will connect to regional or national data infrastructures used by International Alliance members, such as the national BREATHE health data research hub in the UK.",2020,-99,Health Data Research UK,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",, +C07271,C19-IUC-345,Health Data Research Innovation Gateway,"The Health Data Research Innovation Gateway is managed by Health Data Research UK in collaboration with the UK Health Data Research Alliance and funded by UKRI ISCF. It provides a common entry point to discover and enquire about access to UK health datasets for research and innovation. It provides detailed information about the datasets such as a description, size of the population, and the legal basis for access. The Gateway includes the ability to search for research projects, publications and health data tools, such as those related to COVID-19. New interactive features provide a community forum for researchers to collaborate and connect and the ability to add research projects.",2020,-99,Health Data Research UK,,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C07272,C19-IUC-344,Coordinate and connect a national data science driven research effort related to COVID-19.,"HDR UK has established multiple elements in existing data sharing platforms to collate information and provide readily available networks connecting new and established resources for the research community. These include a dedicated Slack channel (#COVID-19challenge), a resource page for GitHub (https://github.com/hdruk/covid-19) and a webpage dedicated to COVID-19 projects led by colleagues from across the institute.",2020,-99,Health Data Research UK,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C07274,C19-IUC-337,Characterising the Global Immune Responses to SARS-CoV-2 in COVID-19 Acutely Infected and Recovered Ugandans.,"The project will address the following objectives: 1) Humoral Responses. (1a) Develop sensitive and specific binding antibody tests for detecting exposure to SARS CoV-2. (1b) Develop functional assays for detecting SARS-CoV-2 neutralising antibodies. (1c) Distinguish memory B-cells to isolate human monoclonal antibodies for therapeutics. (1d) Describe association(s) between detected antibodies and clinical outcome/comorbidities. 2) T-Cell Responses. (2a) Determine immunogenic regions of SARS-CoV-2. (2b) Determine the anti-viral T Cell correlates of protection. (2c) Describe association(s) between T Cell responses and clinical outcomes across risk groups (age, sex, comorbidities). 3) Inflammatory Responses and associated omics. (3a) Describe underlying single cell processes associated with distinct disease outcomes. (3b) Describe cytokine profiles associated with distinct disease. 4) Blood Genomics. (4a) Host genetics signatures associated with control of disease. (4b) Genetic regulation of ACE-2 gene expression. (4c) Host HLAs associated with distinct disease outcomes",2020,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Unspecified,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C07275,C19-IUC-336,Excess mortality in different regions of China during the outbreak of COVID-19: findings from nationwide Disease Surveillance Point system,National death data was used in 605 urban districts/rural counties (population >300m) in the China's nationally representative Disease Surveillance Point (DSP) system to estimate excess mortality during the three-month outbreak of COVID-19 (1st January to 31st March 2020) were calculated and compared with the predicted or mean rates for 2015-19 in different areas.,2020,-99,MRC Population Health Research Unit at the University of Oxford,,Other,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Western Pacific,Western Pacific,,,,China,China,Epidemiological studies,Disease surveillance & mapping, +C07276,C19-IUC-110,COVID-19: MRC COVID-19 surveillance in the Gambia,To support global COVID-19 detection and response in the Gambia,2020,-99,MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Gambia,Gambia,Epidemiological studies,Disease transmission dynamics, +C07277,C19-IUC-089,Identification of host RNA binding proteins that are recruited/required by SARS-CoV-2 during its infection cycle to elucidate therapeutic targets_x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_ _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_,"If immune cells (lymphocytes) are infected by this (SARS-CoV-2), then assumptions that patients previously infected are now immune may be incorrect. The project will devise new methods to detect and visualize SARS-CoV-2 directly in infected human tissues to determine which immune cells could be infected, which sub-class of two types of immune cells (T and B cells) are affected and which immune cells of the digestive tract may be affected. These methods will be able to confirm viral infection in deceased cases where a diagnosis was not made. _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_ _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_ Identification of host RNA binding proteins that are recruited/required by SARS-CoV-2 during its infection cycle to elucidate therapies that target viral replication. The protein synthesis machinery suggested by data to be used by the virus, is currently being explored as an anti-cancer target by all major pharmaceutical companies and there are many drugs that can be used in this regard which have been through clinical trial and are readily available._x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_ _x005F_x005F_x005F_x005F_x005F_x005F_x005F_x000D_",2020,-99,MRC Toxicology Unit at the University of Cambridge,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history", +C07278,C19-IUC-002,MC_PC_19074 - COVID-19: Estimating severity from multiple data sources using Bayesian evidence synthesis,"MRC-Awarded COVID-19 Rapid Response Grant on ""Estimating severity from multiple data sources using Bayesian evidence synthesis"".",2020,-99,MRC Biostatistics Unit,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C07279,AH/V013858/1,Lex-Atlas: Covid-19: A Comparative Study of National Legal Responses to COVID-19.,"Original application: 'The project's core deliverables are a Compendium, a Database and a Final Report by fourteen internationally distinguished scholars on the legal responses to Covid-19 in 80 countries across all regions of the world. The Compendium comprises 80 national reports written by local legal experts on the relevant country's response to Covid-19, covering: (1) the constitutional/legal framework; (2) the functioning of institutions (e.g. legislatures, courts); (3) the core public health measures adopted; (4) the social and economic measures adopted; and (5) key legal measures in respect of civil liberties and vulnerable groups. The Database collates determinate and quantifiable data on these themes, allowing users to conduct comprehensive cross-national comparisons and correlations with other known socio-economic, political and health data. The Final Report will comprise: 1. an analytical overview of the data, identifying response trends and correlations to major socio-economic and health indicators; and 2. an in-depth critical analysis of various thematic areas (e.g. privacy, civil liberties, migration), proposing best and worst practices in relation to different themes as well as overall state performance. The deliverables provide critical comparative data for the assessment of the UK's response to Covid-19 as well as for future pandemic preparedness, in general and with particular reference to several topics and questions identified as critical by UKRI: economic, gender and race inequalities; security and justice; national recovery and transformation; contact tracing; and national security and foreign policy. The project's dissemination plans include a clear and viable impact pathway into decision-making in the UK Parliament as well as in Whitehall.' From the www.lexatlas-c19.org website, more media friendly: ""The Lex-Atlas: Covid-19 (LAC19) project was launched in the fall 2020 and will provide a scholarly analysis of national legal responses to Covid-19 around the world. Updated across 2021, it will be published open-access by Oxford University Press. It is the product of a vast collaboration of legal experts from across the world, led by University College London, King's College London, the Max Planck Institute of Comparative Public Law and generously supported by the UK's Arts and Humanities Research Council. The project is motivated by the need for a comprehensive overview of national legal responses to Covid-19. The pandemic has many facets, and national responses have varied considerably. Quite apart from epidemiological performance, countries have employed emergency powers differently, have had different kinds of institutional disruption, diverged in public health measures, and have had variable social policy coverage and responses to the human rights needs of vulnerable groups. A scholarly overview of these legal responses is required both to assess past political choices and to prepare for future pandemics. Cataloguing them in detail will also be an important contribution to the history of the pandemic. However, the complexity and fluid nature of the subject-matter essentially requires an unconventional scholarly approach. To make the international comparisons valuable, it requires a high degree of coordination between distinguished national legal experts, a large editorial team applying a consistent methodology, and the capacity to change national portraits as the law and policy shifts in line with the evolution of the pandemic. The project seeks to meet this need through a world-wide collaboration between legal scholars. The project's core deliverables include a Compendium of Country Reports, a Database, and a Final Report covering best and worst practices in the views of the project's Editorial Committee. All deliverables will be open-access and data will be held open-source.",2020,2022,University College London,458888.57,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C07280,AH/V013807/1,Online teaching and learning with digitised collections in Higher Education contexts,"This project, submitted to the urgency call for the AHRC Towards a National Collection (TANC) programme, will track and evaluate digital teaching with university museum and cultural heritage collections in the 2020-21 academic year. It will synthesise existing good practice and develop new case studies, investigate the pivot to online delivery of collections-based teaching and learning in universities, and identify gaps in skills, tools and infrastructure, as well as in the availability and interoperability of digital and digitised collections and of collections systems. The project will support university museums and other related collections custodians at a crucial turning point in their rapidly-developing collections work and teaching practice, and create guidance and case studies that will be of wider applicability in the sector. Through the close partnership with a strong and collaborative existing regional network, the University Museums in Scotland (UMIS) group, the project can also take advantage of methodologies and case studies across museums of different sizes, scales, and in the context of universities which employ different teaching modes, cover different topics, and have different strategic priorities. It supports TANC by gathering time-sensitive data on how digitised collections are and could be used for university teaching and learning online, and by assessing areas for potential future investment or collaborations.",2020,2021,University of St Andrews,117526.78,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C07281,AH/V013769/1,Cultural translation and the interpretation of Covid-19 risks among London's migrant communities,"One of the key responses to the Covid-19 crisis is change in individuals' behaviour. The success of social distancing, hand-washing, or the wearing of masks/face coverings all depend on individual members of the community adopting these measures. This change of behaviour relies on accurate, reliable and accessible information about Covid-19 and a good understanding of risks associated with Covid-19 among all members of the community. For this, language and understanding of culture are both crucial. This project will investigate public health discourses related to Covid-19 among linguistically diverse communities in London, focussing on languages of Africa and Asia. London is a highly multilingual community - there are more than 200 languages spoken in London's primary schools. London's multilingual and multicultural communities have access to, and rely on, discourses and information about Covid-19 in several languages. Information provided in English by UK media, government agencies, local authorities etc, is augmented by information provided in the community language and from outside of the UK from official channels as well as social media. London's migrant, ethnic, and minority communities are thus engaged in translating and interpreting Covid-19 information from different sources and often adopting a variety of perspectives, and this will inform their understanding of and their behavioural response to the pandemic. The current project will investigate how information about Covid-19 and associated risks flows and is translated in a range of London's diverse linguistic repertoire of languages such as Standard Arabic, Algerian Arabic, Chinese, Hindi, Indonesian, Japanese, Korean, Persian, Punjabi, Turkish, Urdu, Swahili, and Yoruba. Our goal is to understand how London's migrant/ethnic/minority communities receive information about Covid-19 and how that information and its cultural context impact on their reactions and everyday practice in this environment. For example, Japanese speakers in London have access to at least two free community newspapers and the Japanese embassy sent translations of Boris Johnson's key speech introducing the first lock-down and various Covid-19 related information to registered Japanese citizens. The UK-internal perspective on addressing the Covid-19 crisis is thus contrasted with external perspectives, which are often critical of the UK's approach. In order to understand these multilingual and multicultural discourses, the project will investigate five key questions: (1) How London's multilingual and multicultural communities interpret and translate the information they receive from different sources, including information from their home countries and their local communities, and how this impacts on their understanding of Covid-19 and their social behaviour (2) To what extent communities' understanding is coloured by their different cultural, linguistic and social backgrounds and their processes of cultural translation (3) To what extent some communities are at higher risk of contracting or transmitting Covid-19 because they do not understand relevant public health advice (4) How information about Covid-19 can be better communicated or translated for London's diverse linguistic and cultural communities (5) What lessons can be learned from this pandemic for public health communication in the future The project will draw on the extensive language and cultural expertise at SOAS University of London in collaboration with public agencies and community representatives. It will collect, document, and synthesize individual accounts from multilingual community members in London, information in the target languages published in London, and information available to community members from their (historical) home countries, their governments and on social media.",2020,2021,SOAS University of London,521175.13,Human Populations,Asian | Black | Unspecified,Adults (18 and older) | Unspecified,Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2020 +C07282,AH/V013734/1,Social Distancing and Reimagining City Life: Performative strategies and practices for response and recovery in and beyond lockdown,"COVID-19 has transformed city life: we now urgently need to develop imaginative ideas and creative practices to understand and address its impact on how we live and work in cities. Performance theory and practice offer innovative, proven, yet under-explored means to achieve this. This project will provide new models for understanding and practising city life, helping people cope with social distancing, both practically and emotionally. Working with strategic decision-makers in Bristol, Glasgow and Newcastle City Councils (confirmed), we will investigate everyday innovations (social performances) and artistic interventions (aesthetic performances), to understand how performance can reimagine and facilitate city life in times of social distancing, and how performance theory and analysis might contribute to more nuanced, creative and sustainable strategies and practices for response and recovery across five urgent areas: social cohesion, new behaviours, community resilience, perceptions of environment, and crisis management. Working with artists, arts venues and officers from hazard mitigation, sustainability and resilience, the project will lead to new understandings of the place and function of performance, broker creative thinking on response and recovery, and make strategic recommendations for arts strategy, pandemic planning and hazard mitigation policy. Impacts will be scaled, primarily, through Core Cities, a network of eleven UK cities, and arts strategy organisations. This project builds on the investigators' recent work in New Orleans, which led the Office of Homeland Security and Emergency Preparedness to fundamentally change their hazard mitigation policy and practice, and to significant changes in strategies for major arts organisations (www.performingcityresilience.com)",2020,2022,Northumbria University,162377.04,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts | Other secondary impacts,2020 +C07283,AH/V013122/1,The immobilities of gender-based violence in the Covid-19 pandemic,"One particularly concerning consequence of the Covid-19 crisis is the reported surge in domestic abuse. This transdisciplinary project seeks to produce understandings of domestic violence in relation to gender-based violence (GBV) and immobilities in order to produce insights that can be converted to policy. It does so through the creation and analysis of personal stories detailing experiences of GBV across the UK at different stages in the Covid-19 crisis. The Covid-19 lockdown has focused attention on domestic violence and its relationship to constrained mobilities. Understanding domestic abuse within the frame of GBV allows us to look across the multiple sites of felt violence that have been reconfigured. It is critical that we understand and deliberate GBV in these redefined spaces in order to invigorate policy responses to domestic abuse and other GBV within the current crisis and beyond. This research does so through the analysis of told and untold stories of GBV in relation to the complex interdependencies of immobilities. The project investigates how im/mobilities precipitate gendered violence, both felt and experienced and how embodied experiences become situated in mobile spaces - inside, outside and online - in the context of the Covid-19 pandemic. The project combines analysis of existing stories (in the public domain already) with directed original life writing, supported in creative writing cafes, to develop a form of autoethnography that values narrative accounts of experiences of GBV at different stages of the pandemic and reveals inequalities. These stories will be valued as part of the critical research through academic outputs as well underpinning online conversations with policymakers and professionals with a view to producing tangible policy recommendations.",2020,2021,University of Brighton,141033.2,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts,2020 +C07284,AH/V013017/1,Quality Improvement tool for re-designing healthcare service-user journeys with COVID-19 risk assessment & mitigation,"In order to deliver business as normal performance, healthcare care providers will need to reconfigure almost all services (many currently in abeyance) to accommodate the future challenges of covid-19 (For example; pulsed lock-downs, isolation of the vulnerable, new testing & tracing regimes, disrupted supply chains, new working practices & new spatial demands on facilities). Quality Improvement (QI) approaches currently provide a research informed framework of tools for local innovation in healthcare. A wide variety of QI tools currently support NHS QI work, drawn from sectors like manufacturing. Over the last 12 months NHS Tayside has integrated a services of additional QI tools based on Service Design into its QI Programmes. These design approaches work alongside established QI tools to map the service-user (patient) perspective. This proposal describes the development of an online QI tool that will support the challenge of mapping, evaluating and reconfiguring services that take account of the evolving risks & challenges of COVID-19. NHS Tayside will provide the platform for tool development, NHS Education for Scotland (NES) will provide specialist QI guidance & access to wide networks for dissemination. UoStrathclyde will provide service design research expertise. Development will involve: capturing lessons learnt from recently established COVID-19 pathways, integration of proven service design tools with established risk management tools, collation of research into COVID-19 risks and mitigations, synthesis and testing of tool templates and development of online training to deliver the new tool in a QI context. Tool effectiveness will be evaluated. Knowledge gained will be valuable and widely transferable to other service sectors within the service economy, challenged with redesigning & implementing COVID-19 mitigations.",2020,2022,University of Strathclyde,206192.56,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +C07285,AH/V012835/1,COVID-19: Widening access to arts and culture through video streaming,"Recent years have seen gradually developing digital expertise by many arts and culture organisations focused on physically-sited exhibitions, performances, and events. The closure of venues in the wake of COVID-19 has suddenly put these experiments to the test, and given urgency to arts and culture organisations' need to build capacity for digital programming. So far, video streaming has emerged as by far the most common route for the sustainable delivery of cultural content online. It has also often generated large audiences. Initial research suggests that recent moves to video streaming have widened access to arts and culture. However, it is important that organisations also reach more geographically, culturally, ethnically, and economically diverse audiences. Accordingly, this project will gather and analyse qualitative and quantitative data in order to helping arts and culture organisations achieve two symbiotic goals: to develop digital programming strategies that can reach new and more diverse audiences, and to develop long-term resilience to the economic and cultural impact of COVID-19. Research questions will include: - What forms of, and approaches to, video streaming have proven most effective during physical shutdown, and may best complement physically-sited post-lockdown programming? - Which digital distribution models developed in response to COVID-19 are most replicable across organisations and sectors? - How can successful digital initiatives of the last two months be incorporated into organisations' core work, without sacrificing their pre-existing activities? - What opportunities does video streaming provide for increasing equality of access to arts and culture - both during and beyond the current crisis? The project's findings will feed into the equality, diversity, and inclusion (EDI) policies of Arts Council England's forthcoming 10-year strategy, 'Let's Create', and provide practical knowledge for UK-based organisations struggling to adapt their business models and artistic programmes to a socially distanced world.",2020,2021,University of Kent,212918.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C07286,AH/V012819/1,"Museums, Crisis and Covid-19: Vitality and Vulnerabilities","The Covid-19 crisis is having a significant impact on the museum sector, nationally and globally. It is exposing the vulnerability of museums, their staff, projects and collections. Elsewhere, innovative programming is demonstrating the vitality and versatility of an engaged, responsive and participatory museum service, proving that museums are places of relevance even in a crisis. This research project focuses on how museums can continue to contribute to community resilience and wellbeing in a time of crisis. It addresses sector adaptability as it adjusts audience engagement and collaboration (such as new collecting practices, programming and exhibitions) in response to Covid-19. The differing responses during the Covid-19 crisis - in some museums staff were furloughed yet elsewhere they have been involved in responsive projects - uncovers deeper attitudes to the essential (or otherwise) nature of museum services. Going forward, this project will lead and inform the sector as it adapts to effective community-digital possibilities that still embraces new thinking in participation and engagement. Alongside this, the project evaluates how we adapt our practices to be mindful of audience diversity, digital poverty, and the isolation challenges for vulnerable audiences arising from Covid-19. Rising to that challenge this project: 1. identifies how museum pedagogy and practices must adapt to new audience needs; 2. explores possibilities for co-produced community-digital innovation; and, 3. investigates the offer museums can make to support community resilience during and in the aftermath of the Covid-19 crisis. The importance of this project lies in the following areas. Firstly, new knowledge about the understanding of the impact of Covid-19 on the museum sector in NI that will both inform the Department for Communities (DfC) and have national relevance. Secondly, by generating new thinking around the community-digital dynamic and leading innovation as museums adapt. Thirdly, understanding the new needs around community resilience and wellbeing, arising from Covid-19. The Museums Association's response to the Covid-19 enquiry described museums as vital in supporting communities, promoting community cohesion, enabling wellbeing, and reflection on significant public issues. Many of our museums work with vulnerable groups, who will remain cautious/shielding post lockdown e.g. the Dementia Friendly Programme (NI Museums Council). This project will investigate the impact of putting such programmes on hold, how they can be effectively adapted/reinstated, and make recommendations for immediate application/future planning.",2020,2022,University of Ulster,268339.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Social impacts | Other secondary impacts,2020 +C07287,AH/V012797/1,Touch Post-Covid19: Navigating through deafblindness in the UK via contactless haptic-audio-visual technologies of perception.,"This is a public-facing investigation into the impact of touch deprivation on deafblind communities. Building on an existing interdisciplinary research project (Film and Television, and Quantum Physics) at the University of Glasgow, it examines sense perception through the means of audio- visual impairment and investigates how technologies of perception may augment the sensory experience of deafblind people. Covid19 has acutely heightened our awareness of and restrained us from using the sense of touch. Touching is now threatening lives, but it still remains a vital connection to the world and others. For deafblind communities, who rely on haptic experiences to navigate the world, the fear of touch and intimacy in post-Covid society is likely to impose new challenges and increase social isolation. Working primarily with Deafblind Scotland, and Deafblind UK, and drawing on sensory and media studies, we will create audio-visual documentation of social experiences of selected members, which will aid in understanding their and our new world. We will also develop strategies and new contactless haptic-audio-visual tools/technologies that facilitate safe and reliable communication for individuals. Research findings will reach policymakers, academics, and public audiences through reports that inform policymaking, contactless haptic-audio-visual tools and strategies, online exhibitions and open access data, journal articles, and public awareness events.",2020,2022,University of Glasgow,353577.84,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07288,AH/V012770/1,Ensuring Respect for Human Rights in Locked-Down Care Homes,"Residential care facilities have been at the epicentre of the COVID-19 pandemic, with high rates of infection and high mortality rates. In response, many care homes have been 'locked-down' for extended periods, with expanded restrictions on the liberty both of residents and of those who wish to visit them. Even as the broader society emerges from lockdown, these restrictions continue in care home settings. If/when the restrictions are finally lifted, they are likely to be re-imposed in any care home where a new infection is reported. The aim of this project is to determine how best to ensure that the human rights of residents of locked-down care homes are protected, both during the pandemic itself and in the 'new normal' that is likely to follow. The project focuses on three practices that have been common in care homes during the pandemic: the use of blanket restrictions on the movement of residents and their visitors; the blanket use of ""Do Not Attempt Cardio-Pulmonary Resuscitation"" (DNACPR) orders; decisions to restrict transfer of unwell patients to acute-care hospital facilities. The project addresses two main questions. 1) How should the human rights to (inter alia) life, liberty, and non-discrimination be interpreted and applied to these three practices in the context of a public health emergency? 2) How can existing roles such as best-interests assessors (BIAs) and independent mental capacity advocates (IMCAs) best be adapted to help ensure respect for the human rights of residents who are living and dying in locked-down care homes?",2020,2021,University of Essex,230063.4,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Approaches to public health interventions,2020 +C07289,AH/V012762/1,COVID-19 rumours in historical context,"The COVID-19 outbreak has been accompanied by a pandemic of rumour and disinformation in the UK. Rumours about the origins of the virus, shortages, fake cures and government conspiracies are being spread by well-meaning people who want to make sense of the outbreak, as well as by criminals and hostile foreign governments. These rumours have the potential to cost lives, not least by undermining public confidence in any forthcoming vaccine. Despite the apparent novelty of 'fake news' and its circulation online, there is little that is new about these rumours, all of which have historical precedents. Yet policy-makers know little about how and why similar rumours have spread in the past, how previous governments have responded to them, and how successful these efforts were. At a point in history where rumours about COVID-19 present an unprecedented health challenge, this project will deploy a novel longitudinal study of relevant historical rumours and government efforts to address them in order to assist policy-makers. It will track rumours circulating in the UK relating to the COVID-19 pandemic and any vaccination programme as they develop and compare them to historical precedents. A report, published in collaboration with History & Policy, as well as two closed workshops with policy-makers and scholars drawn from other disciplines, will seek to inform UK government strategies for dealing with mis- and disinformation and influence the tone and content of public information campaigns in order to minimise the harmful impact of 'fake news' and maximise uptake of any future vaccine.",2020,2021,University of London,127809.01,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C07290,AH/V012657/1,An Urgent Review of Single Source Procurement During the Pandemic: Recommendations for Best Practice and Reform,"Public procurement has played a vital role in the COVID-19 response with over 1 billion items of equipment sourced across the UK. However, procurement has not been subject to rigorous analysis. Ordinarily, contracts must be awarded following an open competion. Exceptionally, UK law permits awards to a single supplier without a competition in cases of extreme urgency to minimise delay in delivery. Awards must still be published and clear justifications provided. Yet, hundreds of thousands of contracts have been awarded without full visibility. Further, contracting authorities face immense ongoing pressure to source quickly; suppliers have not been able to access all opportunities; and others have opportunistically charged high prices or not delivered. This project, led by the world-leading Public Procurement Research Group (PPRG) at the University of Nottingham in strategic partnership with the Department of Health and Social Care and the Open Contracting Partnership, will conduct an urgent investigation into single sourcing during the pandemic. The aim is to develop better organisational planning, ensure legal compliance, achieve value for money, and reduce corruption risks in ongoing procurement during the pandemic. The project also aims to lay the foundation for lasting reform which is responsive to a new global political, economic and social reality. To meet these aims, the project objectives will be to: (1) collect and collate evidence of single sourcing through contract data and stakeholder interviews during a defined period; (2) develop a best-practice ""toolkit"" for immediate use by contracting authorities and suppliers; and (3) provide a ""real-time"" comprehensive review of single sourcing, comprising analysis of the evidence and recommendations for policy and legislative reform to inform imminent public inquiries and review exercises.",2020,2022,University of Nottingham,26782.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07291,AH/V012630/1,TRAC: COVID - TRust And Communication: a Coronavirus Online VIsual Dashboard,"The COVID-19 crisis has required mass communication and public understanding on an unprecedented scale. During this time there has been a proliferation of online discussion, news sharing and emergence of 'information sources' concerning COVID-19. Such proliferation has raised concerns about the potential dangers of dis/misinformation. As yet, however, neither the extent of the issue nor the sources of information have been studied in detail. Furthermore, despite communication being at the heart of COVID-19 public health efforts, there has been a surprising lack of input from linguistic experts. This project aims to build a large-scale dataset of Twitter posts, which will be made available via an open-access online dashboard incorporating intuitive visualisations. The dataset will be novel in capturing not just the content of tweets, but also the content of web-pages shared in the tweets. Drawing on automated corpus linguistic methods and social network analysis, the dashboard will uncover the multi-layered content of shared information (original links, tweets, replies, retweets), alongside a deeper understanding of the online networks through which (mis)information is shared. To demonstrate the applicability of our novel approach to a wide range of stakeholders, the methodology and dashboard will be validated through two case studies, each focussing on a potentially dangerous area of miscommunication relating to COVID-19. These case studies will approach the problem from a linguistic perspective, examining the clarity and reception of official messaging and the trustworthiness of information sources.",2020,2021,Birmingham City University,101884.65,Human Populations | Other,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C07292,AH/V012614/1,Comics in the time of COVID-19: Tracking data on web-based comics and evaluating their potential for communicating public health messages,"Our pandemic lives are deeply entwined with visual, web-based public health messages, from instructional hand-washing pictograms to infographics about physical activity during lockdowns. Alongside these official public health communications, people are creating thousands of web-based comics conveying public health messages. It is critical that we collect and code these comics now. As ephemeral, web-based artefacts we risk losing access to thousands of these creations and their specific circulation contexts. Capturing and coding this data now will allow us to rapidly track their messages, reach and engagement. In particular, focusing on web-comics from the first 6 months of the pandemic, we will be able to evaluate the impacts and potentials of producing and circualting time-sensitive public health messages via the comics medium across social media platforms. Capturing these web-comics' reach and engagement on digital platforms will also yield insight into how public health messages are shared and interpretted on social media, as well as into how behavioral change is championed and resisted. Coding will be done through a qualitative content analysis of comics' narratives and visuals, as well as an analysis of social media comments, allowing us to evaluate for evidence of behavioural change and real-time resilience-building in relation to public health guidelines. To maximise the impact of this resource on beneficiaries, key stakeholders from the Graphic Medicine Collective, Information Literacy Group, and Public Health Dorset will help shape data collection and analysis. Research data will be stored on BU's secure cloud service and on external hard drives. The final, deliverable dataset will be in Excel and CSV formats, compatible with web interface, database and digital cataloguing for ease of adaptation for future activities.",2020,2021,Bournemouth University,82489.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C07293,AH/V011561/1,Pandemic Review: Rights and Accountability in COVID-19,"The UK's response to COVID-19 significantly limits rights through a combination of law, regulation, guidance, and policing practice emanating from Westminster, devolved administrations, and police forces. While the UK's human rights obligation to protect the right to life mandates an effective response to the pandemic, the nature and extent of that response carries the risk that rights will permanently be undermined. Review of the pandemic response is key to limiting that risk. It is a critical component of ensuring accountability and legitimacy, which in turn underpins public trust and compliance with pandemic regulations. In order to be effective, review must (i) recognise the wide range of rights-related impacts of the response, (ii) engage substantively with questions of disproportionate impact by characteristics such as age, gender, race, ethnicity, and socio-economic status, and (iii) be able to influence government responses by holding the state accountable for rights (non-) compliance and insisting that rights-limitations are temporary, proportionate, and fully rolled back once no longer necessary. This project will monitor and strengthen pandemic review by establishing a 'COVID-19 review observatory', which will document and analyse the extent, nature and effectiveness of (legal and political) review of the impact on rights. It will produce 'report cards' for pandemic reviews, and feed back to and in to review mechanisms in order to strengthen their accountability functions. The project will thus strengthen review mechanisms' contribution to state accountability and the restoration of rights normalcy 'after COVID-19'.",2020,2022,University of Birmingham,297008.95,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +C07294,AH/V011405/1,Creative Doodle Book: Developing Inclusive Community Arts Engagement during Physical Distancing,"The disruption caused by Covid19 has forced community arts companies to drastically adapt their activities. This has been particularly impactful on organisations working with marginalised or vulnerable people, many without the social or economic capital to access digital arts activities. During 'normal' times, the arts have a vital role in supporting resilience through providing opportunities for positive creative expression. During the Covid19 crisis, it is even more vital to find ways for everyone to express their creativity in community contexts. This project will adapt and extend the 'Creative Doodle Book', a hands-on resource developed by the project PI and Mind the Gap Theatre Company (MTG) in 2019. Through a series of playful tasks and activities, the Doodle Book facilitates creative reflection designed to support personal agency. During May 2020, MTG successfully piloted the at-a-distance delivery of the Doodle Book during lockdown with their network of learning-disabled artists. Building on these positive early indicators, this project will work with MTG, and access champions Totally Inclusive People, to develop the Doodle Book as a model of inclusive physically distanced practice. In a blended approach, this will be accompanied by adaptive support and accessible resources to reach individuals otherwise excluded from digital arts activities. We will work in collaboration with twenty community arts groups, and adopt a train-the-trainer approach to provide a structure that can be expanded at scale. The project will also provide evidence of the role of creativity in wellbeing and personal agency in times of extreme uncertainty.",2020,2021,York St John University,87813.25,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C07295,AH/V014293/1,Performing Leadership Differently: Co-Creating Collective Strategies for Change,"The project will focus on central research question: How can arts, social science researchers and creative communities co-create models of participatory leadership and engagement for BAME and working-class communities within theatre and performance after COVID-19? As part of our research we will pilot and test new leadership models, linking them to the theatre and performance community. The methods that we are using are best suited to a participatory action approach which allow for maximum level of substantive participation from diverse stakeholders. This will allow us to innovate, co-create and share best practices for being able to respond to the crisis and enable diverse constituents in the sector to be heard by policy makers. By co-creation we refer to the participation of subjects and partners in further articulating the central questions of this research. In contrast to previous arts diversity initiatives, the project embeds those systematically excluded from leadership within the arts at every stage of the research, drawing on their expertise to build relevant and effective strategies of investigation. Throughout the project research methods will be adapted in response to participant feedback, to maximise impact, recognising that the practical expertise to combat discrimination and marginalisation lies in engaging, connecting with, and amplifying the voices of those directly affected by forms of institutional exclusion. Engagement with artists, organisations and audience initiatives will be activated to facilitate this through partner Something To Aim For (STAF) a sector support organisation funded by Wellcome Trust to increase diverse engagement in the arts and to support centralising voices on the fringes. STAF's networks include over 500 000 individuals and 73 arts organisations, ranging from Wellcome Collection and The Barbican to SMEs including Raze Collective, HighRise Theatre and Migrants in Culture. Direct engagement with artists and participants will mainly be conducted online, using strategies of digital networking to connect artists and networks who are increasingly fragmented and isolated. Workshops and other group activities will be facilitated through 'Us In the Making', a new digital hub developed to create and sustain communities who have been de-platformed, safely online, in response to Covid-19. Hub functionality allows video conferencing, group interaction and participation, remote hosting and presentation of materials and asynchronous access to documents and files.",2020,2021,Queen Mary University of London,118262.27,Human Populations,Asian | Black,Unspecified,Unspecified,Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07296,AH/V013904/1,'Stay home': rethinking the domestic during the Covid-19 pandemic,"As a site of self-isolation and lockdown, the home is at the forefront of strategies to save lives in the Covid-19 pandemic. The proposed research and its co-created outputs will lead the public debate about home in a pandemic society. Based in London and Liverpool, and in partnership with The Museum of the Home (MoH) and The Royal Geographical Society (with IBG) (RGS-IBG), the research combines a nationwide and city-scale approach in three interconnected strands. 1. 'Documenting home' interrogates the ways in which 'stay home' has been represented, reimagined and contested in political debate and media coverage. It also explores and extends MoH's online 'Stay home' collecting project and will co-curate material for display, deposit and digital engagement. 2. 'Practising home' examines the practices, spaces and meanings of home during the pandemic for migrants, diaspora communities and people of faith in London and Liverpool, both 'hotspots' of Covid-19. Working with adults from different ethnicities, faiths and generations, alongside migrant/diaspora and interfaith organizations, we will co-create short films, podcasts, an interfaith toolkit and material for the MoH collections. 3. 'Mapping home' explores children's changing conceptualisations of home at a time of crisis. Working with the RGS-IBG, its school networks and initiatives, we will co-curate (i) a nationwide map of home spaces for children/young people (aged 7-16) during Covid-19; (ii) a city-scale project in Liverpool City Region to anlayse children's narratives alongside their maps; and (iii) a virtual exhibition, learning resources (KS2-4) and a policy brief on children at home during Covid-19.",2020,2022,Queen Mary University of London,665018.62,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C07297,AH/V013890/1,Collaborative Solutions for the Performing Arts: A Telepresence Stage,"Performing arts professionals must collaborate to create, rehearse and perform. COVID-19 restrictions on shared spaces and physical contact now prevent them from working effectively. This project will reframe and customise conventional web-conferencing technologies to create innovative performance spaces, enabling collaboration in a shared online environment that we refer to as a telepresence stage. Real-time video images of remote performers are merged within virtual stage sets, so participants appear to co-exist in the same online space. This enables actors and dancers to simulate presence together from their homes, studios, theatres, or other remote locations to advance online creation, rehearsal and performance. The project team from media and performing arts backgrounds bring together their knowledge and experience of developing live networked performance research and practice for over 30 years. They will develop a Telepresence Laboratory between University of Brighton UK, Third Space Network Studios in Washington DC and LASALLE College of the Arts in Singapore, combining green- screen technology and virtual set design to enable full-body interactions between remote performers in shared online spaces. Eight UK performing arts groups will test, explore, and perform online techniques. These groups include youth theatre, dance companies, musical theatre and regional theatres, working from remote locations using standard computing and video resources. Each 4-month residency will culminate in a live-streamed public performance demonstrating unique telepresence solutions to be immediately disseminated via multiple easy- to-use PDF help guides, step-by-step video tutorials and open-source resources designed to assist UK performing arts professionals in returning to work regardless of lockdown restrictions.",2020,2022,University of Brighton,260169.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Other secondary impacts,2020 +C07298,ES/V01708X/1,Coping with the COVID crisis in prison,"Prisons have emerged as hotbeds of contagion during the COVID-19 health emergency. To try to prevent the spread of the virus, prisons in England and Wales have subjected prisoners to conditions of severe lockdown, confined to their cells for 23 hours per day, with visits, therapy and education effectively suspended for more than three months. Little is known about the impact of this unprecedented shift in penal conditions on prisoners' mental health and well-being as all prisons research has been effectively suspended during this time. The proposed co-production between Queen's University Belfast and the User Voice charity would represent an extremely innovative participatory research project involving prisoners and former prisoners in leadership roles in every stage of the research from design to analysis. This research project would utilise User Voice's democratically elected Prison Councils that operate in one-fifth of prisons and two-thirds of probation areas across England and Wales, representing around 30,000 people a year. Through this partnership, we are proposing a three-phased, 18-month collaborative project to co-design and co-produce key findings from prisoner insights on the impact of COVID-19 on prisoners with a focus on what should happen next to transition out of the crisis. The research will involve 18 focus groups and a survey to be delivered to prisoners across 9 facilities in England and Wales, all delivered by peer researchers trained by experienced researchers at User Voice and QUB.",2020,-99,Queen's University Belfast,681864.4,Human Populations,Unspecified,Unspecified,Unspecified,Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts", +C07299,ES/V016989/1,Leading school learning through COVID-19 and beyond: online learning and strategic planning through and post lockdown in English secondary schools,"Covid 19 has presented unprecedented challenge to school leaders in England: challenge that intensifies as pupils return to full time schooling. The UK government has issued warnings that schools will close if two or more cases of the virus appear within a fortnight and that schools must offer,'a high standard of remote/blended learning' (DfE, 020720). During the lockdown schools developed online learning strategies, but to date there is little or no knowledge of how these strategies have been led and managed or how they have /or will address the needs of disadvantaged pupils, who are recognised to be disproportionately impacted by school closures. This project takes a three stage mixed methods approach to investigate how school leaders at three levels; head teacher (or CEO), heads of curriculum planning and heads of department, in state secondary schools in England, are strategically planning for the management of online learning over the next 2 years, and how this builds on current practices. Using a case study approach based in 20 schools, the project uses an adaptation of Puntedura's model of differing degrees of technology integration to establish what level of online provision is being offered at present and what plans schools have for the next 2 years (Puentedura, 2012) These are : L1 - Substitution- technologies are used passively to support teaching; L2 - augmentation - traditional pedagogies are adapted for online use; L3 - Modification-strategic thought is given to the design of online learning and enhancements that add value to online teaching are implemented in order to improve learner performance; L4 - strategic planning for design of online offerings linking to whole school/ department approaches in online learning. As such, the project will offer unique insights into the short and medium term planning for online learning.",2020,-99,Open University,319841.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07300,ES/V016652/1,Essential experiences in science: addressing the gap in primary enquiry-based practical science created by lockdown and aiding school recovery,"Focusing on primary science education, we will identify and disseminate strategies to enable UK schools and organisations to increase resilience and counter the impacts of lockdown particularly for disadvantaged students. The Epistemic Insight Curriculum Framework underpins research by hundreds of practitioners in schools and Initial Teacher Education (see www.epistemicinsight.com). Designed to raise teacher confidence and expertise in science education and action research, it summarises UK curriculum expectations for scientific enquiry and literacy and provides tools to track children's progress. Accompanying resources and CPD embed these objectives and tools into hands-on science activities, cross-disciplinary investigations and real-world problem-solving. These established tools and methods will be used here to discover best practice and to test the efficacy of interventions on children's enquiry skills, scientific literacy, science capital, academic self-concept and attitudes to learning. Validated questionnaires will be used in quasi-experimental studies focusing on core variables of interest and pre-post surveys (Gopalan, et al., 2020). We describe and interpret naturally occurring variations in the baseline data and also changes over time where subjects act as their own controls. As the interventions will be tailored for multiple settings, we use linear multilevel models to model these differences as a random factor (Goldstein, 2003). Based on effect sizes established in our previous studies, we believe that our target sample sizes will be more than adequate to detect the effect sizes of interest, even if we face modest dropout. Qualitative work will analyse survey comments and interview studies with children, parents and teachers.",2021,-99,Canterbury Christ Church University,132643.56,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions | Social impacts, +C07301,ESRCCOVID134,Supporting Parents and Kids through Lockdown Experiences (SPARKLE),"Co-SPACE, a UKRI-funded nationwide study of families' mental health during the COVID-19 pandemic, found a significant increase in children's behaviour problems (Cohen's d = .21; p < .001) over the first months of lockdown. Additionally, 70% of respondents asked for extra parenting support. This confirms concerns of an upcoming surge in behavioural challenges in schools and increased parental help-seeking from already overstretched children's services, as lockdown restrictions ease off and families readjust to the 'new normal'. Supporting Parents and Kids through Lockdown Experiences (SPARKLE) is a rapid deployment randomised controlled trial evaluating whether an intervention in the form of a digital public health parenting intervention - Families Under Pressure plus (FuP+) - can reverse these negative effects. FuP+ includes eight animations covering universal evidence-based parenting messages designed to be delivered at scale in an engaging way by celebrity parents. FuP+ animations will be accessed via a mobile application, which will supplement and contextualise the messages to provide easily accessible practical parenting resource. Embedding SPARKLE in Co-SPACE, with pre- and post-intervention measures extracted from routinely, monthly, collected data, will ensure rapid implementation. 616 Co-SPACE participants will be automatically randomised to either FuP+ or follow-up as usual (FAU). This will give statistical power to test whether FuP+ can reverse the negative effects of lockdown by producing a positive effect on behaviour equal in size and opposite to lockdown's negative effect. If results are positive, FuP+ will be disseminated rapidly through collaboration with Public Health England and Department for Education, in cooperation with commercial media partners.",2020,-99,King's College London,667069.48,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts, +C07302,ES/V016393/1,Supporting Parents and Kids through Lockdown Experiences (SPARKLE),"The first COVID-19 lockdown and continuing restrictions on everyday life have presented families with unprecedented challenges. Extended joint confinement, often within very limited space, isolation from friends and family, increased demands on parents to deliver childcare in face of often increased work demands, mental and physical health-related and money-related worries, have placed relationships between parents and with their children under great pressure. Consistent with this, Co-SPACE, a nationwide study tracking changes in families' mental health since early lockdown, found a significant rise in parent-reported children's behaviour problems and associated family-related stress. Strikingly, 70% of parents in Co-SPACE reported wanting additional support preferably delivered in digital form. These problems are likely to persist if left unaddressed. There is also widespread concern amongst professionals that they may increase further as the pandemic continues, and with it the restrictions put on people's lives. Families are faced with continuous need to readjust to new routines, structures and challenges. Although children have returned to school and many parents are able to work outside home, many childcare settings are not fully open, and schools have had to make substantial adjustments to comply with the public health measures introduced to curb the spread of the virus. It seems likely that as the pandemic continues and with it the threat of further severe restrictions, including another lockdown, we will see growing pressures on schools and already over-stretched children's services, as more parents seek additional training, support and advice from professionals. This will further increase the already substantial gap between the need for help and the availability of that help and leave many families without access to vital support. Based on existing research of health inequalities, this is likely to disproportionately affect the most vulnerable sections of society. In SPARKLE, we will examine whether providing families, who have taken part in the Co-SPACE study, with an app delivering information and parenting support, Parent Positive, can reverse negative lockdown-related effects to improve families' wellbeing and reduce pressures on services. The Parent Positive app is built around a series of 45-second animations presenting eight foundational messages about managing children's behaviour, which have been carefully selected by parents and parenting experts for their relevance to the pandemic situation.They are light-hearted, humorous and non-judgemental in nature and are delivered by eight high-profile celebrities who are also parents. The eight messages relate to: (1) staying positive and motivated (Olivia Colman); (2) making sure everyone knows what is expected of them (Sharon Horgan); (3) building your child's self confidence and trust (Danny Dyer); (4) getting your child to follow instructions (Rob Brydon); (5) promoting better behaviour (Jessica Ennis-Hill); (6) limiting conflict (Holly Willoughby); (7) keeping calm when your kids act up (Romesh Ranganathan); (8) careful use of sanctions (Shappi Khorsandi). The animations will be supplemented with a video offering practical tips on how and when to use the animations, extended and more detailed accounts of each message, links to useful sources of help and downloadable resources, as well the opportunity to network to find peer support. To test whether Parent Positive can reverse the negative effects of lockdown, 616 Co-SPACE parents will take part in this study. Half the families will be given access to the app and half will not. We will then test whether the app has a positive effect on children's behaviour compared to not using it. If results are positive, the app will be rapidly made available to families across England through collaboration with Public Heal",2020,2022,King's College London,538334.79,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C07303,ES/V016253/1,COVID-19 impacts on children under 5 in temporary accommodation-co-developing solutions from lockdown to the recovery phase-A mixed-methods study,"The temporary accommodation (TA) environment combined with barriers to accessing early years health services place children under age five (under5s) at risk of increased morbidity and mortality (Burton et al. 1998; Marmot 2020), further exacerbated by the COVID-19 pandemic. Culturally tailored support services and interventions for the health of children living in TA is a recognised gap in current UK health service provisions. Institute of Health Visiting and third sector organisations are urgently calling for targeted solutions and interventions to ensure the short- and long-term impacts of COVID-19 on these vulnerable children is addressed. Building on the research team expertise in participatory, culturally-sensitive citizen science research with marginalised communities, we will describe the National impact of COVID-19 on under5s and their families living in TA and utilize co-production to identify suitable, acceptable and feasible integrated crosssector public health intervention solutions for the recovery phase. These solutions will be contextualised for local application and acceptability but grounded in evidence and learnings from globally recognised effective interventions and be aimed at overcoming access barriers by reaching out to the families and communities (e.g. introduction of mobile health clinics)(Yu et al. 2017). However, for the UK-tailored approach to increase successful implementation of the public health solutions and minimise inequality and inequity gaps faced by under5s living in TA, community and professional engagement will drive the co-development process (Questa et al. 2020). Similarly, engagement with health and social care commissioners will ensure that the appropriate evidence to support adoption and implementation decisions is produced.",2020,-99,University College London,702085.72,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07304,ES/V016245/1,"Care leavers' transitions to adulthood in the context of Covid-19: Understanding pathways, experiences and outcomes to improve policy and practice","Care leavers are at risk of social exclusion and vulnerable to poor outcomes including poverty, homelessness, mental ill-health, low educational attainment and unemployment. They typically negotiate the transition from care to adulthood at a younger age than their peers in the general population. Moreover, they often have to negotiate multiple transitions simultaneously and do so without the 'safety net' of the levels of practical, emotional and financial support that birth families typically offer to their kin. At 16-18 years of age young people leaving care tend to follow one of five transition pathways: Direct pathway: transition from care to independent living in a council flat or privately rented property; Transitional placement pathway: transition to semi-independent living arrangements; Return to birth family pathway: transition from care to return to live with birth family; Formal extended care pathway: Staying put or Staying Close arrangements; Complex: pathways typified by a quick succession of placement moves (adapted from Munro et al., 2012). Management information system data on approximately 900 care leavers in transition will be analysed to explore their pathways and outcomes in the context of Covid-19. In-depth interviews will be undertaken with leaving care managers and workers and with 50 care leavers (at two time points) to examine young people's progress and strengths and limitations in services and support during (and in the aftermath of) the pandemic. The team will work in co-production with care leavers and professionals to develop tools to support best practice to meet the needs of different 'sub-groups' within the leaving care cohort, including those at high risk of poor outcomes.",2020,-99,University of Bedfordshire,399525.35,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Other,Caregivers | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery, +C07305,ES/V016210/1,Children and young people living in poverty: COVID-19 needs and policy implications,"This project addresses the UK's serious knowledge gap in understanding the needs of children and young people (CYP) aged 5-18 living in poverty in the context of Covid19. A North East(NE) regional analysis is required urgently to inform policy decisions being taken quickly without real understanding of lived experiences of poverty. This project will enable policy to consider how best to address children's social, emotional, physical and educational needs. This project that puts CYP's voice at its centre is co-designed and co-delivered by researchers from Newcastle University's Centre for Learning and Teaching and the charity Children North East (CNE). The long-standing reputation CNE has built upon by providing support during lockdown will ensure high engagement by families in the research, and an extensive reach through networks will enable policymakers to make timely use of findings. CYP will be invited to communicate experiences and needs in a format of their choice (writing, picture, photo) and we anticipate a sample of 1500. 500 CYP will be consulted in more depth (face to face/online interviews/focus groups). Twenty interviews with organisations working with CYP will triangulate findings. We will investigate and compare organisational response to CYP living in poverty. Case studies of practice and policy change will be shared nationally as good practice examples. Our regional and national networks will ensure quick and effective dissemination of findings. Outputs from the project include two academic articles, three research reports, two linked policy workshops/webinars, a policy brief, a series of short comics, and an animated video.",2020,-99,Newcastle University,204151.01,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07306,ES/V016202/1,"Impacts of the Covid-19 pandemic on criminal justice journeys of adult and child survivors of sexual abuse, rape, and sexual assault","Over 150,000 sexual offences were recorded by police in year ending March 2020 (ONS, 2020), and there are indications that lockdown increased some sexual offences (e.g. online-facilitated abuse, or sexual abuse perpetrated by family members) and decreased others (e.g. assaults by strangers/peers). However, there has been no research into the specific effects of Covid-19 on criminal justice system (CJS) policies and practices relating to sexual offences, nor on the journeys of survivors through the CJS during this period. Prior to the pandemic, there were significant challenges for the investigation and prosecution of sexual offences and conviction rates were extremely low. Some of these challenges may well have been exacerbated by Covid-19 and lockdown e.g. further delays to investigating cases, postponement of Achieving Best Evidence interviews. At the same time, however, Covid-19 has generated significant innovation within the CJS, e.g. the introduction of a video platform within the courts enabling all parties in a criminal hearing to engage securely and remotely, and this may sow the seeds for improvement in survivors' journeys through the CJS. Drawing on the perspectives and experiences of CJS stakeholders, including complainants and families, police, Crown Prosecution Service, HM Courts and Tribunals Services, the Judiciary, Sexual Assault Referral Centres, and Independent Sexual Violence Advisors, this research will provide unique insights into the impact of the pandemic on the CJS in sexual offence cases. Changes to procedures precipitated by Covid-19 might offer longer-term benefits for survivors and stakeholders and we aim to identify these and promote their implementation.",2020,-99,Coventry University,284334.05,Human Populations | Other,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C07307,ES/V016032/1,"Experiences of COVID-19 and recovery: learning from polyphonic voices for communities, policy makers and health and social care providers","The study aims to improve understanding of the ways in which patients from diverse communities have experienced COVID-19, provide an online resource as part of Healthtalk.org (to inform and support individuals and their families) and to co-produce flexible resources to support health and social care staff, communities and policy makers to 'build back better'. The coming months, while the experience of the first year of the pandemic is still in focus, provide a critical opportunity to capture and learn from people's narratives of COVID-19. Interviewing people about their experience will help us to understand how they made sense (or struggle to make sense) of what has happened to them, the recovery process and their ideas about how services and community support could be improved. We will use interviews to document and understand what it has been like for people living with and through COVID-19 during these exceptional times and then use what we have learnt to develop resources for the public, community and services. OBJECTIVES 1. To understand the different ways in which COVID-19 has been experienced in Britain. We will conduct in-depth interviews with a national, diverse sample of around 75 patients, who have managed/been cared for in different (non-ICU) settings. 2. To develop new approaches to make the research relevant to people from black and minority ethnic communities (BAME), including migrant workers. Our team of researchers with expertise in ethnicity and health will work with their networks and PPI on the design, conduct and application of the research. 3. To develop an experience-based online resource (for patients, public, policy makers, care providers) as part of the online platform Healthtalk.org. This well-established award winning site has, since 2001, published findings from over 110 studies in condition-specific sections, illustrated with video, audio and animated interview extracts. 4. To co-design, with communities, patients, carers, service providers in health and social care practical applications of the findings. This may include (in the shorter term) resources to support recovering (long) COVID-19 patients and learning how to 'build back better' services and community resources. 5. To compare findings with those identified by our international collaborators who are independently collecting COVID-19 narratives. The collaborators from 14 countries worldwide are meeting for workshops from December 2020-2022 to prepare cross country analyses and resources in addition to the existing online platforms (similar to Healthtalk.org in UK) in each country. We have assembled a team with expertise in ethnicity and health (Douglas, Rai, Qureshi), research on patients' experiences (McNiven, Ziebland), General Practice (Salisbury, Dixon), PPI (Ali, Hussain), service improvement (Locock, Hinton) and delivery of online resources (Sanders). Our PPI co-applicants, advisory panels and our wider networks including BAME communities will help ensure that our interview focus, recruitment methods and the resources we create are inclusive and remain relevant throughout and beyond the 18 month project. Outputs include a new COVID-19 section on Healthtalk.org (~75 interviews and 35 themed summaries), catalyst films and a theatre workshop, peer reviewed papers, reports, a methods paper on conducting remote research with seldom heard groups and cross country comparisons with our international collaborators.",2020,-99,University of Oxford,636454.21,Human Populations,Black | Other,Unspecified,Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Caregivers | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health service delivery, +C07308,ES/V015990/1,Investigating The Use Of Temporary Accommodation To House Asylum Seekers And Refugees During The COVID-19 Outbreak,"This project will explore the impact of the Covid-19 outbreak on asylum seekers and refugees living in the UK. As reported by the Home Affairs Select Committee, asylum seekers are at 'heightened risk' in the context of Covid-19. The project will focus on those individuals placed in temporary accommodations such as hostels and hotels, using Glasgow as a base for the project as the local authority with the most dispersed asylum seekers in the UK (Sturge 2020, 14). Recent moves by private sector firms to relocate asylum seekers into 'safe environments' have been widely criticised, particularly for the difficulties in maintaining physical distancing in new crowded, shared spaces thus increasing the risks of exposure to Covid-19 (BBC News, 2020). Organisations and stakeholders representing asylum seekers have reported the fear and distress that this move has caused for asylum seekers (PAIH 2020a). In addition, this re-housing has also made it difficult for charities to provide support to affected individuals, who are moved often at short notice. The project will examine what the situation is currently on the ground, how the crisis has accentuated the risk for those seeking asylum and develop responses with migrant communities to create a genuinely 'safer environment' for asylum seekers. Adopting digital ethnographic methods (Lupton, 2020) co-designed and co-produced with grassroots migrant organisations, the project will deliver longer term impact through the development of co-produced creative outputs including a documentary and work with outreach groups to influence UK government policies and public debate on asylum.",2020,-99,Edinburgh Napier University,71113.77,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07309,ES/V015982/1,Understanding and learning from the impact of COVID-19 on probation's work to improve the health of people under its supervision,"Individuals supervised by probation are more likely to have certain health problems than the general population, often having multiple physical and mental health problems. Poor health can negatively impact on criminal justice outcomes like reoffending. In partnership with healthcare organisations, probation work to identify health needs and improve the health of people under supervision. Probation replaced office appointments with email, Skype and doorstep visits in response to the pandemic, and models of partnership working between health and justice agencies have adapted, changing how healthcare is accessed. The nature and impact of these changes for those under supervision isn't fully understood. Concerns have been raised that existing difficulties that this vulnerable group encounter with accessing healthcare may be made worse. However, the pandemic may also have led to helpful innovations in how healthcare is provided that need to be captured and spread. Following discussions with several senior probation staff, NHS England and individuals with lived experience of the criminal justice system, we have created a proposal to address this knowledge gap and thereby inform future policy and practice. We will use staff survey data and correspondence, and service user interviews to improve understanding of the nature and impact of Covid-19 responses on a) health-related probation practice, b) the lived experience of seeking health support whilst under probation supervision, and c) partnership working and pathways into care. Revolving Doors are key to capturing service user views. Through joint working with stakeholders findings will directly inform how services are provided in the future.",2020,-99,University of Lincoln,62956.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Economic impacts | Health service delivery, +C07310,ES/V015974/1,"Rapidly formed COVID-19 teams in the NHS: implications for leadership, team-working, career intentions and individual mental health.","A key component of the NHS (and global) response to the COVID-19 pandemic has been to reinforce acute and critical care capacity, through an unprecedented re-deployment of personnel from different care pathways into fluid teams consisting of volunteers, student doctors and nurses, and in some cases military personnel [1-4]. These COVID-teams provide a unique opportunity to examine the interaction of many of the established factors for successful delivery of medical teamwork and care. Current evidence suggests that without common teamwork, shared communication patterns and clear leadership structures, the ad-hoc and fluid nature of these COVID-teams increases risk to patient outcomes, delivery of care [5-9] and team member resilience, mental-health and retention [10,11]. This project will examine how non-technical factors for healthcare delivery (leadership, social support & cohesion, communication, shared mental models, co-ordination) and expected moderating factors (occupational background, preparedness, work-life balance, home situation, proximity, workforce allocation models) impact on perceived COVID-teamworking and performance, individual team member well-being and team member employment retention intentions. It will be a mixed methods cross-sectional exploratory study of COVID-team members, clinical directors and senior hospital managers across a wide range of partnered NHS Trusts. Qualitative interviews will identify key themes and will be followed up by a more widely recruited confirmatory survey examining longer term individual well-being and retention intentions. Throughout, there will be a high emphasis on rapid dissemination of results to NHS partners and wider medical and other stakeholders to inform evidence-based workforce guidance and accelerate team-working theory, practice and policy.",2020,-99,Oxford Brookes University,409820.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Military Personnel | Health Personnel | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance | Health workforce, +C07311,ES/V015958/1,Did the Furlough Scheme and Mortgage Holidays Prevent Mortgage Default?,"The COVID-­‐19 crisis has inflicted serious financial hardship upon UK households. By May 2020 14% of borrowers were behind on their mortgage payments. To mitigate the economic damage, the government introduced unprecedented economic policies that provide income and job protection support. We investigate to what extent the Coronavirus Job Retention Scheme (furlough) and the mortgage holiday (MH) policy introduced by banks reduced the incidence of mortgage default during the crisis. By safeguarding jobs and subsidising a worker's monthly wages, the furlough scheme may allow distressed borrowers to avoid default and continue making monthly mortgage payments. MHs may directly lower the incidence of default by deferring repayment until a later date. However, their limited duration may constrain the policy's effectiveness and shift the timing of default to the future. We develop a model of mortgage default that incorporates both policies. Using the model, state-­‐ of-­‐the-­‐art macroeconomic methods, and household survey data collected since April 2020 by the Understanding Society database, we quantify how many defaults the policies prevented. We do so at the national and regional levels because the economic impact of the pandemic has impacted UK regions to varying degrees. Furthermore, we study whether the policies have different effects according to a borrower's age, ethnicity and income which influence savings and a person's ability to withstand an income and employment shock. Our research helps understand the effectiveness of the furlough and MH policies, and provides guidance to tailor and optimise their future design.",2020,-99,University of Birmingham,94096.17,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C07312,ES/V015893/1,Investigating how nurse education prior to and during Covid prepares nurses for the pandemic : an analysis of what works,"The Covid-19 pandemic has changed the face of healthcare delivery and has placed ever changing demands on nursing care. This qualitative study will use audio, visual diaries or written diaries kept over four weeks of a clinical placement and telephone or on-line interviews at the end of the placement, to gather data from second and third year student nurses in England, Wales, Scotland and Northern Ireland. Student nurses will describe their experiences of education both before and during the pandemic (including between the first and second waves) and their experience of on-line learning, commenting on what went well and what could have been done better. They will also identify any transferable skills they acquired and how these may be used in nursing to provide optimal care throughout the different phases of the pandemic and beyond.The study will investigate the psychological wellbeing of student nurses and the extent to which their experience within the Covid pandemic influences their identities as nurses and their intentions to pursue a career in nursing.",2020,2022,Oxford Brookes University,651062.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2020 +C07313,ES/V015877/1,"Health, social, economic and cultural impacts of COVID-19 on migrant essential workers in the UK","1.2 Scientific/technical summary (max. 250 words) COVID-19 has exposed the UK's socio-economic dependence on a chronically insecure migrant essential workforce. While risking their lives to offset the devastating effects of the pandemic, migrant workers reportedly find themselves in precarious professional and personal circumstances (temporary zero-hours contracts, work exploitation, overcrowded accommodation, limited access to adequate health/social services including Universal Credit). This project will investigate the health, social, economic and cultural impacts of COVID-19 on the migrant essential workforce and how these might impact on their continued stay in the UK. It will focus on the largest non-British nationality in the UK, the Polish community, who - while employed across a range of roles and sectors - are overrepresented in lower-paid essential work. We will use this group as an illustrative case study to make wider claims and policy recommendations about migrant work during the pandemic. Using a mixed-methods approach, we will conduct: an online survey to map COVID-19 impacts; in-depth qualitative interviews to establish how the pandemic has affected worker's lives; and expert interviews with stakeholders to investigate how to best support and retain migrant essential workers in COVID-19 recovery strategies. The results will generate the first comprehensive UK-wide dataset on the experiences of migrant essential workers against the backdrop of COVID-19. The research, co-produced with partner organisations (Polish Expats Associations, Fife Migrants Forum, PKAVS Minority Communities Hub and Polish Social and Cultural Association), will generate a policy briefing, a toolkit for employers in the essential work sectors, information resources for migrant workers, alongside media and academic outputs.",2020,2022,University of Glasgow,334162.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C07314,ES/V015850/1,Domestic Abuse: Harnessing Learning Internationally under Covid-19 (DAHLIA-19),"There is considerable evidence that, both in the UK and globally, the risks of living with domestic violence and abuse (DVA) have increased consequent to Covid-19 restrictions. A range of responses at policy and practice levels have emerged. These differ across states and their take-up and impact are unknown. Capturing diverse responses and early evidence of impact can influence approaches to further lockdowns and contribute to planning for lifting restrictions and recovery. This study harnesses the global nature of policy and practice responses to DVA under Covid-19 by examining policy and practice responses in the UK; Australia; Ireland and South Africa. These have been selected as upper or upper/middle income countries with established DVA services. The Connect Centre for International Research on Interpersonal Violence and Harm will utilise its established partnerships to convene online stakeholder meetings with policy shapers and service providers in all four countries. These will generate key questions and contacts to inform a mapping and rapid review study that will collect innovative policy and practice examples together with documentary and other evidence across all four countries. Critical appraisal by an international panel of a selected sample of initiatives will enable in-depth study. The research will consider whether responses address all family members: victims, perpetrators and children. This focus will acknowledge that experience of DVA is gendered and differentiated within the family and evokes responses from different policy and practice spheres. Consultation and reporting will be iterative and embedded to achieve early and targeted knowledge transfer.",2020,2022,University of Central Lancashire,245190.82,Other,Not applicable,Unspecified,Unspecified,Other | Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Europe | Western Pacific,,,,United Kingdom,United Kingdom | Australia | Ireland | South Africa,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C07315,ES/V015842/1,Optimising Outcomes from Procurement and Partnering for Covid-19 and Beyond: Lessons from the Crisis,"Procurement accounts for £100bn (47%) of local authority (LA) spending (IoG,2018). Leveraging these resources to the greatest social and economic effect is now crucial in promoting an agile crisis response, maintaining community resilience and helping local businesses stay afloat. Emergent literatures indicate that innovation to leverage procurement for additional positive-sum value is both necessary and possible (NAO,2016; Amey,2019; PWC,2019; NCVO,2020; LGA,2017; WCPP,2019). This connects on the ground with a new urgency and impetus for change. As LAs pivot and flex in response to Covid-19, and the need to leverage resources accelerates, this research asks how can LAs maximise the impact of, and leverage additional value from procurement? An expert academic team, with extensive stakeholder engagement and support from important project partners, will deploy a robust and agile suite of methods (longitudinal surveys, interviews, workshop/webinars, mini-investigations, e-Delphi study) to provide detailed cross-functional, inter-sectoral, and multi-level analyses of procurement practice and performance. This will mark out critical-success-factors and points-of-failure across the whole system, crucially considering how things vary in different LAs with different characteristics. Its focus and reach makes this a first-of-its-kind study, at the time it is most needed. A strong communications plan will enable rapid harnessing of ideas, data and legal advice to practical, positive-sum procurement solutions, and incentivise patterns of stakeholder relations that combine complementary capabilities in response to current challenges. The parallel development of a 'procurement impact tool' will facilitate new data-analytic capabilities, further accelerating innovation and improvements in practice, performance and strategic decision-making.",2020,-99,University of Stirling,506585.03,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07316,ES/V015834/1,"The impact of COVID, lockdown and subsequent easing on recovery in an ongoing international study of people in recovery from drug addiction","Addiction is a chronic relapsing disorder that causes significant harms to individuals, families and communities, and addiction recovery is a fragile and complex process. The study extends an existing NIHR and Horizon 2020 research cohort (from the ERANID programme, and so is a rare 'active' cohort study in the addictions field). There have been three rounds of data collection on recovery pathways by gender, with an outcome study follow-up rate of 85%. This provides the foundation for assessing change in wellbeing and functioning during the lockdown period and in the transition to easement. Standard measures of sobriety, wellbeing, recovery capital, physical and psychological health, and social and family support, will be repeated with additional measures of online recovery group involvement and family engagement. The proposed research hypothesis is that continued engagement in family activites and peer-based recovery support groups will result in better wellbeing and outcomes. In contrast, where there is reduction in family and social support and in recovery group participation, there will be a significantly enhanced risk of relapse and of psychopathology. The study will assess how gender has an effect on social and recovery support pathways to recovery, with the hypothesis that females will be more reliant on generic social capital and males on recovery group belonging as protective factors, based on existing research by the research team. The study will provide evidence on the effectiveness of online supports and identify gender-specific risks and intervention strategies to support addiction recovery.",2020,-99,University of Derby,183081.15,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C07317,ES/V015826/1,Why do households repay their debt during COVID 19 crisis? well-being and financial implications.,"The project examines the impact of the pandemic and government interventions on household debt repayments and on household financial resilience, measured as months during which households can pay for subsistence consumption and debt with liquid assets in case of income loss. Lockdowns by reducing household spending and employment stimulus packages (i.e. furloughing) have affected debt repayments. Monetary expansion and debt repayment moratoriums have reduced household debt burdens. In addition, household specific characteristics, such as ethnicity, age, gender, assets, health, employment could interact with the above. The project uses a plethora of data to analyse household debt repayments and financial resilience also in light that supportive government interventions are going to be faced out while also lockdowns vary.",2020,-99,"Birkbeck, University of London",135854.18,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07318,ES/V015818/1,Capitalising on COVID-19 as a Trigger for Positive Change in Food Waste Behaviour,"The COVID-19 lockdown has been a big contextual change in people's daily lives. However, it has resulted in positive changes in food waste-related behaviours as indicated in the reports of the Waste & Resources Action Programme (WRAP) and UK media (WRAP 2020a; Guardian, 2020). For example, UK consumers reported an increased awareness and willingness to minimise household food waste leading to a 34% reduction in food waste across 4 key products (bread, milk, potatoes, and chicken) compared to the average across 2018-2019. While the changes seen during the COVID-19 lockdown are promising, behaviour change resulting from temporary contextual changes may not last long (Fuji et al., 2009). We argue therefore that there is a need to run interventions that build on the current momentum to support long-term behaviour change. Considering existing research on consumer food waste behaviour under lockdown, our study is unique and adds value by targeting the need to support positive behaviour change with rigorously evaluated interventions. Our project will (1) identify the factors that have affected food waste behaviours under lockdown, (2) develop, implement and systematically evaluate interventions to support positive behaviour change, and (3) use our partnerships with WRAP and Zero Waste Scotland to disseminate the outcomes across the UK. The outcomes of the project will have positive economic impact on UK consumers' cost savings in relation to their food shopping, as well as environmental impact on the amount of resources and inputs required and greenhouse gas emissions generated, by not producing food that becomes waste.",2020,-99,University of Leeds,356858.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C07319,ES/V01580X/1,"Virtual Justice: Enhancing accessibility, participation and procedural justice in family courts and tribunals during the COVID-19 pandemic","Perceptions of accessibility and fairness are central to civil order and the legitimacy of the legal system and state. COVID-19 and social distancing rules have forced radical changes upon the justice system with many trials now having to take place online from participants' homes with no one being present in a physical courtroom. There is currently no online support to prepare members of the public for appearing in court from their own home or to guide them around these new virtual spaces. This poses a number of challenges to the validity of the process with many interest groups expressing concern about due process and the dangers of alienating court users from the process. There are particular concerns about the ability of the digitally impoverished, vulnerable and other lay users to participate effectively in this new way of doing justice. Working in partnership with Her Majesty's Courts and Tribunal Service this project will draw on existing research and extensive consultation with the public, court staff, interest groups, practitioners and policy makers to produce a central repository of good practice materials and a series of audiovisual guides. It will be guided by the five key goals of enhancing technical competence; improving understanding of court processes; supporting court users in navigating the alternative geographies and sense of time in virtual space; engendering a sense of journeys to and from civic space; and promoting dignity and gravitas in virtual court proceedings.",2020,-99,University of Oxford,347800.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C07320,ES/V015788/1,Investigating the impact of the Covid-19 outbreak on stranger sex offender behaviour and victim vulnerability,"In times of crisis, we know that offenders continue to commit crimes, and do so in a manner afforded by the new context (Thornton & Voigt, 2012). Sex offenders are versatile (Lovell et al., 2019), and change their offending behaviour in accordance with the opportunity to offend (Woodhams & Komarzynska, 2014). The Covid-19 outbreak is a crisis that will alter offender behaviour, as well as who is vulnerable to sexual violence and in what circumstances. Our research is highly urgent because, in the UK and internationally, the police and other stakeholders need to know now how to protect people from new vulnerabilities to sexual violence created by Covid-19, and support those victimised. Sexual violence is a shadow pandemic that should be a key priority in planning a Covid-19 response (UN Women, 2020). We are in a unique position to fill this research gap, documenting the 'who, what, when, where and how' of stranger sexual offending (Leclerc et al. 2016), pre-, peri-(and potentially, post-) Covid-19, and across shorter time-periods defined by differing local/national restrictions. Our project partner, the Serious Crime Analysis Section (SCAS) of the National Crime Agency, has a unique, large dataset of serious stranger sex offences that will be subject to repeated, multi-level analyses using our complementary expertise in analytical techniques from the social and engineering sciences. As well as being of urgent relevance to stakeholders, our research will bring new insights to the sparse literature on situational crime prevention and sexual offending (Chiu et al., 2020).",2020,-99,University of Birmingham,318508.4,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C07321,ES/V01577X/1,Youth economic activity and health (YEAH) monitor,"This project will address the UK's need for robust evidence on the pandemic's consequences for youth employment, learning and psycho-social well-being. It will comprise five related work packages: Transitions, Career Planning, Internships, Training, and Employment Initiatives. Using longitudinal quantitative and qualitative methods, we will examine successful transitions from school into jobs and post-18 education; investigate the association of future optimism and career planning with youth well-being; analyse the consequences of the emergency on internship provision and training, and track local employment support provision and careers education initiatives. To contextualise British trends and to illuminate the potential for policy initiatives and the broader role of institutions, we will compare changes in youths' job market transitions and career planning in the UK with detailed findings for Germany. We will commission a survey of 16-24-year-olds in Britain, conduct qualitative interviews with local labour market stakeholders, analyse a range of secondary labour market data. The project will address social inequalities in the epidemic's impact and assess varying prospects for recovery among places and socio-economic groups defined by age, gender, region, ethnicity, educational attainment and job skills. This study will generate intelligence to facilitate urgent, evidence-informed decision making. Taken together the research will illuminate how future career planning, job-related skills acquisition and local employment support initiatives can come together to help (especially vulnerable) young people to maintain employment, get back to work, and develop productive skills. In so doing, it will examine potential mechanisms to avoid long-term 'scarring' effects for careers and lifetime earnings.",2020,-99,University College London,462101.85,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07322,ES/V015761/1,The Impact of Covid-19 on Recent Graduates' Career Decisions and Outcomes,"The Covid-19 crisis has a potentially profound impact on those entering the labour market, in particular recent graduates, seeking to gain a return on their human capital and access to appropriate forms of employment. Using a mixed methods longitudinal approach, this research investigates how the Covid-19 crisis is experienced across the most recent graduate population, its impacts on their career behaviour and outcomes and which graduates may be most affected. It aims to inform future policy on facilitating graduates' access to fair and sustainable employment outcomes. Viewed as a 'shock event' that is outside of individuals' control (Akkermans et al, 2020), the Covid-19 crisis potentially destabilises otherwise clearer and purposive transitions into employment and forces people to re-appraise careers plans and aspirations. This can be either transient or result in longer-lasting scarring effects that deplete individuals' capacity to (re)integrate into the labour market. Responses may also vary across individuals and groups depending on their life situations and dispositions. Career development literature shows that for external challenges such as recessions and pandemics like Covid-19, career resources and behaviours are important influences in how well people cope with negative career experiences and develop strategies and goals (Savickas, 2012; Brown et al, 2012). Such resources include access to networks, crucial labour market knowledge and adaptability and resilience (Tomlinson, 2017; Peeters et al, 2019). However, these may not be evenly acquired across the graduate population depending on their personal circumstances and background profiles. The current context raises significant equity issues around graduates' employment prospects.",2020,-99,University of Southampton,61936.77,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07323,ES/V015745/1,Safeguarding Victims of Domestic Abuse during Covid-19: Challenges and Opportunities,"The overall aim of the study is to inform the development of national safeguarding policies and practices regarding domestic abuse (DA) in pandemics and other emergency situations. The World Health Organisation (WHO, 2020) warns of an increased risk of DA in emergencies, including epidemics. Domestic homicides in England have risen 50% since lockdown, with substantial increases in calls to national domestic abuse (DA) hotlines (The Guardian, 2020a). Safeguarding refers to protecting the rights of adults and children to live safely and taking necessary steps to protect them from abuse having (reasonable) regard to the wishes of the individual/s concerned alongside a positive duty to promote well-being and positive outcomes. Safeguarding is embedded in statutory guidance (DoE, 2019; DoHSC, 2020) and operationalised via multi-agency working. Safeguarding practices of agencies that aim to identify, respond and support families experiencing DA has changed during Covid-19, but little is known about the impact of such changes (cf. SafeLives, 2020). The study's objectives are to: • Investigate how Covid-19 impacts domestic abuse safeguarding interventions, roles and processes; • Identify examples of good practice, challenges, multi-agency relationships, new work practices and innovation during lockdown and as lockdown unfolds; • Analyse the effect of Covid-19 on the identification of DA victims and the support offered to them by different safeguarding agencies; • Document survivor perspectives including Black, Asian and Minority Ethnic (BAME) survivors living with DA during the pandemic and their experiences of help-seeking; • Contribute to the development of national safeguarding policy and guidance during pandemics and beyond.",2020,-99,Manchester Metropolitan University,360715.95,Human Populations,Asian | Black | Other | Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07324,ES/V015737/1,"The Youth Justice System's Response to the COVID-19 Pandemic: Implications and impacts for policy, practice and justice-involved children","The project's overall aim is to explore the impact of COVID-19 on each stage of the youth justice system. It has eight work packages and investigates four specific research questions. The project will focus on: 1)The impact of COVID-19 on justice-involved children (including service provision,education, employment, and well-being) 2)Adaptations to working practices across the youth justice system (including youth justiceteams, courts and the secure estate) 3)Barriers and enablers to adaptation of working practices 4)Recommendations for policy and practice Drawing on pre-existing networks and partnerships, we will provide an exceptionally rich in-depth case study (gathering qualitative and quantitative data) of the Greater Manchester region. Smithson (PI) co-convenes the award-winning Greater Manchester Youth Justice University Partnership (GMYJUP)-a partnership between the Manchester Centre for Youth Studies (MCYS) at Manchester Metropolitan university and the ten regional Greater Manchester youth justice services. We have already secured access to participants including justice-involved children aged 15-18, youth justice professionals and national policy makers.",2020,-99,Manchester Metropolitan University,403587.17,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts, +C07325,ES/V015729/1,Supporting the interviewing and legal representation of crime victims and suspects using digital communication methods: Is it remotely possible?,"Reacting to COVID-19 required significant, immediate changes to Government processes including the Criminal Justice System. Police investigations must continue, and victims, witnesses and suspects of crime must be interviewed. However, social distancing means that investigators are unable to conduct interviews, and legal/third party professionals are unable to communicate with clients in a traditional format. Thus, remote communication is one such way currently being conducted across the UK, however, this is not standardised ant the current research-base to prove its efficacy is extremely limited. The research team comprises experts in the field and will work in collaboration with our national and international partners who include the National Police Chiefs Council (NPCC), the College of Policing, various police forces in England and Wales, Fair Trials, the National Appropriate Adults Network (NAAN), the International Criminal Court (ICC) and the Commission for International Justice and Accountability (CIJA). We will produce timely and much-needed evidence-based reports and resources to enable immediate and direct impact for our partners and stakeholders. These resources will be available at key stages of the project in order to facilitate shared good practice around two main aspects (comprising four Work Packages): (i) the challenges of conducting interviews remotely via digital means in attempts to gain detailed and accurate information, and (ii) the impact of not having legal and other third party representatives in physical attendace to represent suspects (particularly vulnerable ones) in the police station.",2020,-99,Northumbria University,351391.32,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C07326,ES/V015710/1,The role of the neighbourhood environment in shaping the mental health consequences of Covid-19,"The aim of this proposed research is to test to what extent features of the neighbourhood environment moderates the mental health consequences associated with the coronavirus pandemic. While undoubtedly any mental health impact will be partly shaped by individual characteristics, we also posit that there will be differential vulnerability across people due to their neighbourhood environment. Our starting point is Understanding Society (UKHLS), a survey which collects online data relating to people's mental health. Each individual has a unique identifier meaning that we can track their mental health before, during and after the lockdown, and indeed monitor their mental health on an ongoing long-term basis. Of particular importance for this project is the geographic identifier attached to each individual in the survey. This geographic identifier will allow us to identify the local authority in which each individual lives (391 of these in the UK) and through a special licence application, the lower super output area commonly referred to as the neighbourhood (over 32,000 of these in the UK). Using these identifiers, we will spatially link our longitudinal household survey datasets recording individuals' mental health with a variety of publically available datasets relating to neighbourhood contextual information (e.g. economic and social deprivation, population density, environmental capital, health services etc.). This will allow us to identify what makes some neighbourhoods produce better outcomes than others. Ultimately, our research will help in identifying those most vulnerable to the coronavirus pandemic and in formulating place based policy interventions aimed at protecting people's mental health.",2020,-99,Muhammad Waqas,271488.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C07327,ES/V015699/1,MH-CAT: A longitudinal survey of the mental health of children in State Care in England through the COVID-19 pandemic,"The impact of the current Covid-19 pandemic on the vulnerable group of children growing up in State Care is unknown. This research, which maps on to the UKRI Covid-19 priority of establishing 'social and psychological impact upon vulnerable groups', aims to establish new information on the impact of the Covid-19 pandemic on mental health of children in State Care through a prospective, longitudinal survey. At any given time in England, there are nearly 80,000 children being looked after by the State. Children in Care constitute a most vulnerable group of children in society, with more than 60% of these children having histories of severe maltreatment such as abuse or neglect. Fifty percent of children in Care have a diagnosable mental health concern, when compared with 12% of children in the general population, with research further indicating poor adult mental health outcomes. Despite this, there is a dearth of knowledge on the longitudinal patterns of mental health and the impact of a pandemic situation on children in Care. This research aims to fill this gap in knowledge with information collected directly from children in Care aged 11-18 years, over an 18-month period, through the Covid-19 pandemic. The results, covering a wide range of practice and policy relevant questions about children's mental health and the influence of their placement, schooling, social work support, strength of support networks and their contact with birth families will be useful to local-level managers, practitioners and national-level policy makers in making key decisions about children in Care.",2020,-99,University of Bristol,275812.74,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C07328,ES/V015680/1,Exploring remote working practices for patient public involvement and engagement in health and social care research - responding to Covid-19 and rising health inequalities,"This study has been prompted by the shift to remote forms of working in patient public involvement and engagement (PPIE) brought on by Covid-19 prevention measures. Due to shielding and social distancing the usual ways of involving the public (such as face-to-face meetings and events) are not possible and, even with the easing of lockdown, remote working is likely to continue. This creates particular challenges for ensuring access and engagement from all parts of society. There is a digital divide that maps onto existing socio-economic inequalities, and PPIE conducted remotely has the potential to further disenfranchise already disadvantaged groups. This study aims to facilitate and improve ways of doing PPIE remotely and increase the diversity of public contributors in health and social care research. Our objectives are to: 1. Understand the barriers and facilitators to remote working, by: a. Exploring public contributors and PPIE professionals' experiences of remote PPIE. b. Exploring public contributors' preferences for different types of remote working. 2. Develop mechanisms for implementing improvements in remote working and ways to increase diversity in PPIE by: a. Conducting a rapid review of research and 'how to guides'. b. Develop training packages. We will recruit public contributors involved in research projects across the UK: the NIHR, charities, universities and other research organisations and people involved professionally with PPIE. This is a mixed-methods study with: surveys, qualitative interviews, and a discrete choice experiment. We will produce an analysis of how remote working in PPIE is affected by socio-economic and health inequalities, make recommendations for improving practice and develop training packages.",2020,-99,University of Liverpool,231691.32,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07329,ES/V015672/1,Migrant Remittances and Covid-19: Practices of Care during Crisis,"It is predicted that Covid-19 will wipe out US$100 billion in remittance flows, constituting the sharpest contraction since tracking began in 1980 (World Bank, 2020). This decline, driven by reduced capacities among sending communities, is coinciding with escalating need as the pandemic takes hold in many receiving communities. Given its sizeable migrant population, the UK is a significant originator of remittance flows (Migration Observatory, 2020). The British government's response to this remittance emergency aligns with global efforts to 'keep remittances moving' (DFID, 2020). While important, this raises significant questions about the extent to which policy is able to support the resilience of remittances and respond to this unprecedented challenge. Situating remittances as practices of care, and focusing on Somali, Brazilian and Indian migrants in London, Cardiff and Glasgow, this project addresses three lacunae. First, it examines shifts in the nature, patterns and direction of remittance sending in response to Covid-19, tracking the impact of the pandemic on migrants' labour market experiences, BAME migrants' vulnerability to the virus and the needs of transnational families. Second, it redresses a bias in remittance studies by exploring the implications of disrupted remittance flows on migrant (as opposed to recipient) wellbeing. Third, it investigates how migrants' access to remittance services has been affected by Covid-19, and the impacts of increased digitisation of financial services. Deploying mixed methods combining digital methods with secondary analysis, the project's findings will be immediately relevant to cross-HMG work on protecting remittance corridors, and government and NGO stakeholders working with migrant populations.",2020,-99,Queen Mary University of London,545173.65,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C07330,ES/V015664/1,Covid-19: Industry Level Origins of Fluctuations in Growth Rates and Economic Welfare,"The impact of the COVID-19 shock on the UK economy has been heterogeneous across sectors, suggestive of significant reallocation as the economy recovers. Government support for the economy will therefore need to be targeted at specific sectors in order to be effective. We can observe sector-level stock prices and dividends, and estimate wages, but cannot observe directly how expectations of their long-run growth rates and sector sizes have shifted in response to the COVID-19 shock. However, using an asset pricing theory model (based on an extension of work by one of the applicants [Bhamra, Kuehn and Strebulaev (2011)] we can use sector-level stock prices and dividends and wages to derive equations linking these variables to expected long- run growth rates of dividends and wages across sectors. We can hence estimate sector-level expected long-run growth rates and show how they have changed in response to the COVID-19 shock. We can also estimate the contribution of each sector to aggregate welfare in terms of labour income and consumption and show how these contributions have changed over time. By basing our analysis on asset prices, we can update our estimates of sector-level growth rates In real time. This is important, because sector-level macroeconomic data often lags events (e.g., UK sector-level data on output for February 2020 was released by the ONS on 9th April 2020). Existing work has exploited asset prices to estimate aggregate growth rates for the US [see Gormsen & Koijen (2020)], but no such work exists at the sectoral level.",2020,-99,"Imperial College, London",248072.93,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07331,ES/V015621/1,Understanding the impact of the Covid-19 crisis on UK manufacturing and identifying priorities for renewal through innovation,"This project seeks to address and mitigate the social and economic impacts of the COVID-19 pandemic on the UK manufacturing industry. The pandemic is having a profound effect on UK manufacturing. There is an urgent need for action if we are to limit the scarring effects of the pandemic on the future of UK manufacturing. Improving innovation capability within manufacturing firms and across manufacturing supply chains is going to be important if we are to ""build a future which is greener, safer and healthier than before"". This project will: 1.Understand the manufacturing landscape post lockdown (by month 6). The project will start by gathering a clear picture of the effects of Covid-19 on UK manufacturing firms and supply chains. This will be done through a large scale survey combined with a smaller number of interviews. 2. Identify vulnerabilities and explore scenarios for UK manufacturing supply chains (by month 8). Using data from phase 1 and existing understanding of UK supply chains, the research team will analyse areas of vulnerability. Working with scenario experts, they will then develop a number of scenarios that will be useful for policy makers and those involved in manufacturing in the UK. 3. Provide insights into developing innovation capabilities that will help secure a stronger future for UK manufacturing (by months 12). The researchers will use their existing academic knowledge, combined with the data from phases 1 & 2 to identify some of the targeted actions that could help UK manufacturing to develop innovation capability, within the firm and also across supply chains. 4. Develop an audit tool for innovation capability across supply chains (month 15) and use it to analyse one supply chain that is identified as vulnerable (month 18).",2020,-99,Jill MacBryde,368895.45,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07332,ES/V015605/1,Forecasting and influencing product returns and fraud rates in a Covid-19 world,"Covid-19 has significantly aggravated the problem of high product returns rates, which have been increasing over the last few years. This is a significant challenge for retailers and society, causing economic, social and ecological harm. Returns lead to added complex processing, transportation and wasted resources, as many products cannot be resold and risk going to landfill. Online shopping thrived during the lockdown, and many retailers extended their returns periods. A surge of product returns arrived when non-essential retailers reopened. Problems that are costly in normal periods (e.g. wardrobing, fraudulent refunds, serial returners) have become worse in this pandemic period. With recent research showing that many customers will retain their new online shopping habits, the problems will stay, too. We will conduct a consumer survey, interview 25 retailers and work closely with 5 retailers (letter of support attached) to improve our understanding of consumer behaviours in a pandemic. We will then model this at micro and macro levels using explainable artificial intelligence (AI) techniques to forecast returns and fraud rates in a world dominated by Covid-19 conditions. To mitigate this, we will develop a set of measures, indicating the expected effectiveness and environmental impact. The ultimate goals are to help retailers operate efficiently and thrive in this challenging time, avoiding the need to cut jobs and thereby increasing the financial burden on welfare. This project will uniquely combine behavioural research with the development of explainable AI that retailers can use to mitigate the economic and ecological effects of product returns.",2020,-99,Regina Frei,298986.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07333,ES/V015559/1,SMEs and the macroeconomic response to Covid-19,"We propose to study the effects of lockdown and other UK government policy responses on small and medium enterprises (SMEs). Our model will incorporate SMEs into a general equilibrium model of the UK economy, allowing us to understand important spillover effects of policies directed towards SMEs on wider economic outcomes, including earnings and employment. The particular advantage of our approach is that it permits analysis of the welfare of firm owners as well as the effects of government policies on the underlying factors determining firms' ability to borrow. Our approach also permits analysis of the conditions under which firms' financing and business decisions contribute to increases in wider financial instability, and how policies can be designed in a way that reduces the incentives for firms inadvertently to increase financial instability and exacerbate the effects of crises.",2020,-99,University of Kent,142021.39,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07334,ES/V015508/1,How the design of bankruptcy procedures impacts macroeconomic and employment outcomes in the post-Covid recovery period: lessons from previous crises,"We propose to investigate how the design of bankruptcy procedures impacts macroeconomic outcomes, and whether the design should be different in normal times and during times of economic distress. The Covid-19 crisis provides motivation for our proposed research. Government assistance has allowed some businesses to cover their operating costs, despite declining revenues. Nonetheless, the debt of these businesses continues to accumulate and as the crisis persists this may force businesses into bankruptcy. In the post-Covid recovery phase, some of these businesses will have permanently low revenues and will need to close. The majority of them, however, will be viable, and a way must be found to bring their debt down from distress levels. Renegotiating the debt of distressed yet viable businesses is the subject of bankruptcy procedures. Yet, standard procedures are likely to be of little help during the Covid-19 recovery. This is because the procedures are lengthy and available in practice only to the largest firms. The crisis threatens the survival of a large number of small and medium firms as well. If these firms go bankrupt at a wide scale, the crisis will deepen, and there will be large knock-on effects. In Balloch et al (2020) we propose a revised bankruptcy procedure, which includes an automatic write-down on government claims on a firm in exchange for write-downs by the firm's private creditors. We propose to build on this work and investigate in more depth the interplay between bankruptcy procedures and the macroeconomy. We plan to study this issue both theoretically and empirically.",2020,-99,Simeon Djankov,283710.28,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07335,ES/V015494/1,"Social Trust, Crisis Perceptions, and Viral Misinformation over the Course of the Covid-19 Emergency Period","Effective mitigation of the coronavirus health crisis partly depends on trust that the measures which are being imposed are worthwhile, and that the people who have decided them are trustworthy. Such basic trust has come under pressure over time, partly as society has become more questioning, and more recently through the spread of conspiracism online. There is some evidence of online actors exploiting the current emergency to generate distrust and undermine vaccine confidence. Widespread sense of insecurity - whether health-related, or due to economic hardship - may also sharpen distrust of authority. Undermining of public trust may inhibit return to stronger lockdown measures, the management of exit from lockdown, rollout of testing and contact tracing, and introduction of vaccination programmes. Governments and public health bodies accordingly need high-quality evidence on the sources of distrust and noncompliance, and on the health and public security threats posed by the dissemination of conspiracism. We will analyse whether endorsement of conspiratorial accounts of the pandemic undermines trust and compliance, or whether the relationship works the other way around. This will be delivered through robust analysis of new, high-quality survey data tracking both those who endorse conspiratorial views and those who do not over the coming months. Subject to their agreement, we will also sample respondents' posts from a popular microblogging service, to track their online information sharing against their reported attitudes, identities and behaviours.",2020,2022,University of Bristol,501295.62,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C07336,ES/V015486/1,"Removing rights from the vulnerable: the impact of COVID-19 Social Care ""easements""","The Care Act 2014 places obligations on local authorities to help to improve service users' care and wellbeing. However as part of the COVID-19 emergency powers, local authorities are allowed to suspend the application of certain provisions under the Act by using what are known as ""easements"". Considerable concern has been expressed that the easements may have an adverse impact upon the fundamental rights of service users, who include some of the most vulnerable persons in the community. This project will examine the short- and longer-term impacts of these easements on service-users' fundamental rights. Its focus is upon their application in four diverse local authority areas in the Midlands containing locales of acute social deprivation (Birmingham, Coventry, Solihull and Warwickshire). The research will be undertaken in partnership with Central England Law Centre, which is based in Birmingham and Coventry. The Law Centre's involvement will be of critical importance in assisting in mapping the issues and facilitating access to relevant interviewees. The project will provide a comprehensive examination of the legal basis for, and the nature and rationale of, easement powers introduced by these local authorities. Interviews will be undertaken with key stakeholders, including local authorities, legal practitioners and social care workers involved in the implementation and application of the easements. It will set out the practical impacts of the easements on individual fundamental rights during the pandemic itself and also explore the potential broader longer-term impacts on health and social care rights in the provision of local authority services.",2020,-99,University of Birmingham,276699.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07337,ES/V01546X/1,Mobilising the Voluntary and Community Sector to Address the Unmet Needs of the UK LGBT+ Population during Covid-19.,"It has been long-established that the UK's LGBT+ population faces significant disadvantage and inequality. Research suggests that UK LGBT+ people are not only more likely to experience threats to safety and harassment, but are also more likely to have poorer mental health outcomes, to more regularly engage in substance abuse, and are disproportionately affected by homelessness and familial rejection (Hudson and Metcalf, 2016; Government Equalities Office, 2018). Evidence also suggests that specialist VC sector organisations are a crucial source of support for the UK LGBT+ population, as lesbian, gay, bisexual, trans and non-binary people are discouraged and prevented from accessing mainstream support services through fears of inappropriate treatment and discrimination (Hudson and Metcalf, 2016). Preliminary international and small-scale regional UK research indicates Covid-19 is having a significant detrimental impact on the already disadvantaged UK LGBT+ population, resulting in decreased mental wellbeing during lockdown, threats to personal safety as a result of unsupportive home environments, and problems accessing health care and medication (Commonwealth Equality Network, 2020; LGBT Foundation, 2020). Correspondingly, LGBT+ VC sector organisations report unprecedented demand for services, alongside a loss and/or reduction in staff and funding as Covid-19 negatively affects crucial and already scarce statutory and grant funding (TUC, 2014). Within this context, this project, undertaken by NatCen Social Research and Consortium, in partnership with Stonewall, LGBT Foundation and Intercom Trust, will undertake mixed-methods research to identify and explore the impact Covid-19 has, and will continue to have, on the UK LGBT+ population, and how the LGBT+ voluntary and community (VC) sector can be mobilised to address community need. This project will undertake three key strands of research. First, it would collate and analyse raw online survey data on the self-reported impacts of Covid-19 on the UK LGBT+ population. This data has been collected throughout April-June 2020 by our partner organisations and provides the largest UK data resource on the impacts of Covid-19 in areas such as mental health, social connectedness, safety and service engagement. Second, this project would undertake focus groups to elucidate survey findings, providing disaggregation on the impacts of Covid-19 on vulnerable sub-populations, including BAME, older and disabled LGBT+ people, amongst many others. Third, it will work directly with the UK LGBT+ VC sector; hosting workshops to explore research findings and developing a national strategic framework that will map community need and service delivery, to identify how the sector can be mobilised to address unmet need.",2020,2021,NatCen Social Research,120697.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C07338,ES/V015451/1,A National Observatory of Children's Play Experiences During COVID-19,"The devastating health impacts of COVID-19 have resulted in major restrictions on where, when and how children can play. Play is strongly connected to children's wellbeing and social development and is a crucial means through which children express concerns about, and responses to, the world around them. A collaboration between the UCL Institute of Education, the University of Sheffield, V&A Museum of Childhood, British Library, and Great Ormond Street Hospital, will establish a 'National Observatory of Play' to capture children's experiences of the pandemic. Via social media, national press and our collaborating organisations' networks, we will invite children, their parents and carers, to share stories, thoughts and ephemera connected to play in the pandemic by uploading text, image, sound or video files. With children as observers and reporters of their experiences, the Observatory will document indoor, outdoor and imaginary play, including digital play, from onscreen games to social media. It will illuminate our understanding of the social, material, linguistic, spatial and temporal worlds of children, throughout lockdown and beyond. With our partners, we will develop an online exhibition, a public archive, a radio documentary, and 'Play Wellbeing Toolkits' for talking and listening to children in times of anxiety. We are interdisciplinary academics, archivists and practitioners, experienced in exploring forms of contemporary and historical play, working with children, parents and carers as co-producers of research. Our findings will offer insights into the often-overlooked worlds of play and peer cultures, informing policy and practice during the pandemic and the 'new normals' beyond.",2020,-99,University College London,335602.89,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C07339,ES/V015443/1,National recovery and resilience: learning from elections during a pandemic,"Urgent policy decisions need to be made about the conduct of elections worldwide during the pandemic, not least in the UK. Elections in at least 72 countries were postponed due to COVID-19, between February and October 2020. Others have continued to hold elections - but with some adjustments such as introducing special voting mechanisms to adapt their elections to the health crisis. It is essential for national recovery and societal resilience that lessons are learned and disseminated urgently from countries that do hold elections. Most notably, Britain is scheduled to hold elections in May 2021. These will be a 'bumper' set of polls combining scheduled local elections with those postponed from May 2020 because of the Covid pandemic, such as 40 Police and Crime Commissioner elections, the 2020 round of English local elections in 118 councils, local and combined authority directly elected mayors in England, including the Mayor of London and Greater London Authority (GLA). These will be run on the same day as Scottish and Welsh Parliamentary elections, and Police Crime and Commissioner elections, meaning that Great Britain in its entirety will be at the polls, but with no direct previous experience of doing so under pandemic conditions. What can Britain learn from the holding of polls elsewhere? The continuous suspension of elections will deny citizens their democratic voice, and ability to hold their elected representatives to account. However, holding elections without suitable adaption to the health emergency could threaten to accelerate the spread of the disease, by bringing millions of voters, candidates, administrators and officials together on election day. It could also compromise the integrity of the election if citizens are deterred from voting because of concerns about their own health. Issues with any extension of additional accessibility measures, such as extended polling times, or remote voting, whether postal or by alternative methods, may also throw the tension between participation and electoral integrity into sharp relief. This project draws live lessons from states and territories that have continued to hold elections. It will involve the publication of country case studies as technical papers shortly after those elections are held. It will also involve the conduct of surveys of electoral officials. The project will draw out comparative lessons from the case studies about the mitigating steps that can be put in place to protect electoral integrity during the covid-19 pandemic. Findings and analysis about the success, or otherwise, of these COVID-19 mitigations will be used to develop policy recommendations for the stakeholders involved in the organisation of the elections in the UK and in other countries. During 2021, the comparative case studies will be drawn together as an edited volume and published open access with view to generating broader longer term recommendations about how states can prepare in advance for future natural disasters such as an epidemic. It will therefore have longer lasting effects on preserving democracy and electoral integrity, thereby building national recovery and societal resilience.",2020,2021,University of East Anglia,121611.21,Human Populations,Unspecified,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07340,ES/V015435/1,Childcare and Wellbeing in Times of Covid-19: Developing crisis-resilient care solutions,"Government-measures such as lockdown and social distancing have proved successful in the spread of Covid-19 and its burden on healthcare systems. Yet, these policies have exacerbated intense childcare challenges for many families with young children, particularly for families in more vulnerable circumstances, with potentially long-term harm to employment, child-outcomes, wellbeing and relationships. There is urgent need for crisis-resilient solutions of high-quality childcare provision reaching all families in order to mitigate the impact of future waves of Covid- 19-infections. The objectives of this project are two-fold: firstly, it will collate an evidence-base providing the most comprehensive picture on how the Covid-19 pandemic has affected families' childcare arrangements and wellbeing in the short and longer term. This will include collection of rich new data (in-depth interviews with parents and stakeholders) identifying the specific childcare needs and challenges of families in different circumstances (including socio-economic background, protected characteristics and geographical area), and its triangulation with secondary analysis of a wide range of data-sources on Covid-19 impact (including nationally representative surveys and convenience samples). Secondly, in partnership with local and national stakeholders and policymakers, the project will develop a co-produced policy-toolkit providing community-based implementation and practice pathways to support Local Councils' crisis responses and to inform national early years and school-care policy. The innovative project-design combining a comprehensive array of data analysis with a collaborative co-production strategy for local service solutions will be pioneering in designing resilient childcare provision that protects family wellbeing during this pandemic and beyond.",2020,-99,University of Edinburgh,408462.95,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C07341,ES/V015427/1,Supporting separated migrant children to thrive during COVID-19,"Almost 14,000 separated migrant children (SMC) applied for asylum in the EU in 2019 (Eurostat 2019). Without parents/caregivers close by, their connections to support networks, to social work, education and legal services, and to peers are vital. The impact of the COVID-19 pandemic on these networks and services poses urgent risks for SMC's well-being and ability to thrive, socially and educationally. The project aims to examine how SMC (aged 12 -18) experience the COVID-19 crisis and how it has impacted on their connectivity to networks and services. It will identify how services have adapted to meet their needs and will disseminate good practice throughout the UK. An intervention which gives SMC the opportunity to articulate their feelings about this and other crises, while developing English language skills, will be introduced and evaluated. The research adopts a conceptual lens which assumes that for SMC, COVID-19 is likely to be only one of many crises they have faced; in contrast for services, COVID-19 represents the first crisis of this scale. The interdisciplinary research team will adopt a mixed methods design. It combines online interviews with children, their carers, guardians, social workers and teachers; interactional data from the intervention alongside children's blogs/narratives/poetry, and online discussions with stakeholders. Findings will inform the development of an online resource, comprising briefing and working papers and children's work and commentaries. On-going collaboration with UK partners and online workshops and conferences will accelerate impact and build resources to support work with SMC during the current and future crises.",2020,-99,University of Stirling,206177.93,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C07342,ES/V015419/1,UK SMEs: quantifying their pandemic risk and credit risk exposures in the wake of the COVID-19 crisis,"Small and medium-sized enterprises (SMEs) constitute a critical pillar of the UK economy. More than 99% of the roughly 6 million businesses in the UK are SMEs and they employ more than 16 million workers in 2019. As the impact of COVID-19 pandemic becomes clearer, it is evident that SMEs are faced with serious and unprecedented challenges, including declining revenues, defaulting on loans, inability to retain employees and postponing growth plans. There is, however, little detailed attention to their risk exposures and resilience towards funding shortages and how to urgently support them in their economic activities. The project is in collaboration with the Bank of England and Confederation of British Industry (CBI), leading business lobby group, that promotes business interests with government and deals with the impact of policy on businesses in the UK. We will use Artificial intelligence (AI) techniques including Machine Learning (ML), Deep Learning (DL), and Big Data: 1) to quantify the pandemic risk exposure of each SME through constructing a novel Pandemic Risk Index (PRI); and 2) to assess SMEs' credit risk accurately and efficiently by developing a novel Python programme suite (AI_CREDIT). Both PRI and AI_CREDIT will rapidly fill an urgent need by helping policymakers and lenders to make funding decisions based on a comprehensive quantitative analysis of pandemic risk and credit risk exposures at the enterprise level. Overall, this project is directly aligned with the UKRI Priority Area: ""Modelling, AI, digital and data approaches to understanding of the COVID-19 pandemic and mitigating its effect"".",2020,-99,University of Nottingham,397027.61,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07343,ES/V015389/1,"Should I stay or should I go? - NHS staff retention in a post COVID19 world, challenges and prospects","Across the UK the Covid-19 pandemic has imposed unprecedented demands on NHS staff and resources. Issues of capacity - in trained staff, hospital beds, and other vital equipment (PPE and ventilators) - have been critical in determining government policy in managing the crisis. Staff shortages and finding ways to increase rates of staff retention is a long-established challenge for the NHS but, comes into even sharper focus in the context of managing Covid-19 cases, as well as the backlog of care / treatment delayed by the pandemic. Little is known of the impact of the expeeence of the acute demand for services during spring 2020, and the unknowable profile of demand over coming months on NHS staff resilience, in particular their capacity and willingness to continue to meet the unprecedented demand for care, and associated impacts on their health and wellbeing. This research sets out to answer the questions: (i) How will the Covid-19 pandemic impact on staffing resources in the short and longer term? (ii) How long will NHS staff be able/prepared to meet the amplified job demands directly associated with the epidemic and the backlog of demand for non-COVID treatment? (iii) What impact will the legacy of the COVID-19 crisis have on the resolve of NHS employees to remain in the NHS employment? (iv) What might need to change to sustain current NHS employees remaining; motivate those who returned in response to the request from the UK Government and attract recent leavers to return to NHS employment? These questions will be answered using date from an array of complementary sources: a bespoke UK-wide NHS employee survey; case studies of four NHS Trusts and interrogation of established (secondary) data sources (the UK Labour Force and NHS staff surveys). The return of substantial numbers of ex-NHS staff (~27,000), following the Government appeal, is of notable interest, as it directs attention to an untapped resource normally lost to the NHS.",2020,2022,University of Bath,432542.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2020 +C07344,ES/V015370/1,Assessing the Impact of COVID-19 and COVID-related Decision-Making on Forced Marriage Vulnerability in the UK,"COVID-19 and COVID-related decisions are having significant impacts on children and adults vulnerable to, and already experiencing, the crime of forced marriage. Our mixed-methods project will chart and understand this impact, inform evaluation of the UK's response to COVID-19, and shape on-going policy regarding the UK's pandemic response. We consider the uneven economic and social impact of the pandemic, and the ethical dimensions of unequal impacts of COVID-related decision-making, on this vulnerable group, and seek to impact how government, civil society and the voluntary sector support vulnerable people.",2020,-99,University of Nottingham,305906.65,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C07345,ES/V015354/1,Augmented feedback to enhance motor and artistic learning during social distancing,"Social distancing has produced an indefinite shift to remote teaching. This shift poses unaddressed challenges in delivering classes and providing feedback remotely for physical activities such as performing arts or rehabilitation. Digital technologies can facilitate or enhance learning but little is known about remote motor skills teaching, hence there is an urgent need to identify the best practices for remote teaching of physical and artistic disciplines. The lessons learnt in this project will be transferable to any motor skills teaching, such as rehabilitative exercise or practical skills. We will build on (a) Queen Mary University of London facilities and expertise including an online teaching platform, experts in psychology, dance medicine, physiotherapy, cognition and learning, artificial intelligence and multimedial signal processing, and (b) a collaboration with established dance partners (e.g. English National Ballet school, Laban Conservatory, FloorBarreTM) and Barts Health NHS Trust. We will validate the efficacy of different remote teaching methods and tools on physical and artistic training including artificial intelligence augmented feedback. By focusing on remote training for dance we will not only shed light not on a specific popular discipline but on the remote training of a broad range of traits that include physical skills (from flexibility, muscular endurance and power, joint range of motion), psychological state (mental health, concentration, motivation and their relation to this pandemic), artistic development (presence, rhythm, creativity). Human expert assessment will provide immediate results useful to plan teaching, training data for machine learning for behavioural tracking for personalised feedback. Project outcomes include best practice identification and new tools to mitigate social distancing effects on physical, psychological, artistic, and cognitive outcomes. This will be applicable to performing artists, patients with injury, and ultimately the general public.",2020,2021,Queen Mary University of London,310919.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C07346,ES/V015346/1,"Recovering from COVID-19: Informing, supporting and developing guidance for local resilience","Recovery is ""the process of rebuilding, restoring and rehabilitating the community following an emergency"" (HMG Emergency Response and Recovery, 2013). For COVID-19, recovery will involve all-of society (because everyone in the country has been affected to some extent) and whole-system (because every organisation, service and function has been affected). Since the start of the COVID-19 pandemic we have deployed our research expertise in emergency response and recovery to support government. This has involved providing ongoing information about recovery, producing rapid response guides on aspects of response and recovery, and identifying opportunities for research to support the recovery effort. This project builds on this initial work to understand how government develop plans for short-term, transactional 'recovery' and how they think strategically about longer-term, ambitious, transformational change which we call 'renewal'. Objective: This project works closely with resilience partners in three Local Resilience Forums (LRFs) to develop a generalizable, theoretically underpinned framework for how recovery and renewal to COVID-19 can enhance resilience. The framework will: - Take a whole system approach to recovery and renewal (from communities to national levels) - Explore how to manage the changes in people, places and processes that is needed to live with COVID-19 - Address short-term, transactional recovery as well as longer-term, transformational renewal - Complement existing guidance and resilience standards and inform an international standard that we will write on recovery and renewal Approach: The framework will be informed by (and inform) Recovery Coordination Groups (RCGs) by using an action research approach to work closely with the resilience partners and engage with local and national organisations on how they plan recovery and renewal on a system-wide basis. Our partner LRFs have different structures (e.g. for local governance and recovery governance) and characteristics (e.g. partnerships, priorities, populations, local challenges, inequalities) so we can create a framework that is widely applicable to local variations. Activities: We will: - Collect and analyse national/international lessons on recovery and renewal - Gather primary data by interviewing experts across the world on emergency planning, risk, and resilience - Contribute to three Recovery Coordination Groups (RCGs) as well as three specific renewal projects (e.g. on volunteering, community resilience, demand management in emergency services) - Extensively engage with other local and national government organisations to ensure alignment of our framework and exploit ongoing opportunities for impact - Facilitate webinars and training on recovery and renewal for resilience - Develop and test a framework for recovery and renewal, refine it in different contexts (national and international), learn about its application, and use feedback to improve it - Develop and test a methodology to assess the impact of the framework Main deliverables: - A searchable database of lessons for recovery and renewal for local resilience - Expert briefings on how to implement recovery and renewal for resilience - A generalizable, theoretically underpinned, practice-tested framework to support government's thinking about recovery and renewal for resilience - A self-evaluation methodology to reflect on recovery practices - Publish fortnightly 'The Manchester Briefing on Recovery and Renewal' currently distributed directly (and through a network of national/international partners) to 52,000 people along with case studies and training products - International and national standards having a global impact",2020,2022,The University of Manchester,878145.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",,2021 +C07347,ES/V015338/1,Understanding the financial impact of COVID-19 on the UK care home sector - implications for businesses and the workforce,"This project addresses the impact of COVID-19's on the care home sector including the consequence for the workforce and users while assessing its financial viability, as well as requirements for recovery and resilience. The UK depends on the financial sustainability of the mainly privately-owned care home sector, which cares for over 400,000 older people. Prior to the pandemic, the Competition and Markets Authority 2017 report highlighted the financial fragility of the sector. It is clear that COVID-19 has exacerbated financial pressures on care homes, potentially leading to highly disruptive closures. Although there is a growing understanding of the additional costs to the care home sector attributable to COVID-19, there is a lack of knowledge about the implications for the financial sustainability of the sector as a whole, as well as for different types of organisation (e.g. large chains, charities, family-run care homes). Yet, it is essential for policy makers to comprehend these financial impacts if they are to design effective interventions to ensure the stability of care home provision, maintain safe standards of care and deliver good quality services. This new research will complement the analysis of care costs being undertaken by other relevant research conducted by the ESRC Sustainable Care programme. According to the 2019 report produced by the Skills for Care charity, the 600,000-strong care home workforce is characterised by low pay, high staff turnover and vacancy rates, and reliance on migrant labour. Given the difficulties in recruiting and retaining care home workers prior to the pandemic, policy makers also need to understand and address the financial impact of COVID-19 on staff experiences and efforts to retain staff.",2020,2022,University of Warwick,472937.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +C07348,ES/V01532X/1,Financial lives and wellbeing in low-income groups post Covid-19 (FinWell-Covid),"This study builds on two pre-existing samples of low-income individuals in Glasgow (n=69) and Lambeth & Southwark in London (n=29) in whom we explored the relationship between their financial lives and their health and wellbeing. Methods used were: (1) an intensive financial diary, documenting all incomings and outgoings over a six-month period; (2) combined with monthly interviews, to collect quantitative and qualitative data, including health and wellbeing; and (3) two Q methodology studies (n=93) which explored the wider issues of perceptions, not only of the sample but also professional stakeholders, on causes of and solutions to health inequalities in such communities. The similar mixedmethod study we now propose presents a unique opportunity to identify, in depth, changes in the wider social determinants of health induced by COVID-19 itself as well as its associated interventions (e.g. social distancing and isolating) in some of the most economically-vulnerable members of society. This would be done by continuing to work with our previous samples, some new additions and with the various responsible finance and civil society organisations through which participants were recruited. Data would be collected via a new financial diaries app and continuing with interviews via remote technology. An online Q study would also be conducted, but, this time, with a focus on perceptions of COVID-19 and societal responses to it. These data will be useful in enhancing the acceptability of, adherence to and effective delivery of evidence-based strategies for future prevention and containment.",2020,-99,Glasgow Caledonian University,424663.68,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07349,ES/V015311/1,Mitigating the spread of COVID-19 in mass transit using behavioural science,"As societies are re-opening citizen re-enter public space and many begin commuting to work or school again. Dense cities that rely on cramped public transport, typically the economic power houses of countries, are especially at risk of a renewed acceleration of infections with COVID-19. Governments issue public guidelines such as maintaining social distance, avoiding touching surfaces that many people touch, and avoiding touching one's face. However, these guidelines are hard to follow as they require to change behaviours which are habitual and take place unconsciously. Yet there is a dearth of evidence on how to promote such behaviour change. This project will use insights from behavioural science to design and test the efficacy of interventions aimed at increasing compliance with recommended behaviours. We will collaborate with Transport for London (TfL), with support of the Department for Transport (DfT) to implement a randomised controlled trial on the London underground. We will test the effect of different communication materials on trains on reducing face and surface touching and maintaining recommended distances. We have already obtained approval from DfT and TfL for using advertising space on several lines and planned out safe ways for data collection on target behaviours. The study can be immediately implemented and results will be available after a short intervention period. The results will be scalable. We will provide reports that spell out clear and practical recommendations on how to support behaviour change in a multitude of settings.",2020,-99,King's College London,61948.74,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C07350,ES/V01529X/1,Business Creation in the UK,"We will construct and analyse a population-wide dataset of firm creation in the UK using Companies House administrative data. We will use this data to understand the economic implications of COVID-19 on geographic regions and economic sectors of the UK. An important advantage of our project is that it provides a real-time snapshot of the state of the economy based on the entire company register for the UK economy. This coverage avoids underrepresentation or bias implicit in existing survey-based approaches. Our data can be broken down at the regional or industrial level and we can inspect the effects on business creation at a daily, weekly or monthly frequency. This coverage and granularity is our main value-added.",2020,2022,University of Kent,319677.47,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07351,ES/V015281/1,"Mobilising Voluntary Action in the four UK jurisdictions: Learning from today, prepared for tomorrow","The overarching aim of this four nation comparative study is to critically evaluate social welfare voluntary action responses to the pandemic, to help guide the UK volunteer effort to support the national recovery and prepardeness for future crises, and indoing so inform UKRI research questions on inequality and national recovery (1). The four nation study will be delivered by a UK-wide team (academics, the four key sector infrastructure bodies for each nation), supported by a Project Partner advisory panel (from professional networks, organisations and related ESRC investments). It has been co-designed, and will be co-delivered practising the principles of co-production. The analytical framework is a theory-based evaluation technique (2) with refinements from process evaluation of complex systems (3). A desk-based collection of evidence will be undertaken across the four nations facilitated by CoIs (Q 2.2) from the infrastructure bodies and supported by Project Partners (2.3). Key evidence: national voluntary action policy documents; virtual interviews with policy makers; rapid evidence gathering via voluntary action pro-forma (CoI and Project Partner networks) and anonymised data from matching apps/ platforms. A common coding frame will be employed for data analysis, within country analysis preceding integrated analysis, linking the four nations to identify similarities and differences. Critical feedback and validation will be provided by Project Partners (second Advisory Panel meeting). Emerging findings will be shared via an interactive website; regular webinars; mid review briefings to inform recovery, end of review briefing informing future planning, presented at virtual end of award events (one per nation).",2020,2021,Northumbria University,478523.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07352,ES/V015273/1,The role of Health and Safety Representatives in COVID-19,"Workplace health and safety representative have legal rights to represent the interests and concerns of workers over health and safety, to make representations on potential hazards and dangers and to have contact with health and safety inspectors from the Health and Safety Executive or the local authority (HSE,2020). In a pandemic their independence from but relationship with management is potentially critical in assessing and addressing risk for workers and for public health. This research identifies the role that health and safety representatives have played during COVID-19, lessons learned and best practice for future waves or pandemics. It examines organisational and sectoral mechanisms and processes for worker voice and representation and effective social dialogue and joint regulation on health and safety. It explores the potentially key part health and safety representatives are playing in the return to work and productivity. They are not only essential to independent risk assessment and the provision of Personal Protective Equipment (PPE), but also the organisation of work and workplace ergonomics, including the challenges of continued home working. They are central to the protection of mental health, ensuring that health and safety measures cover all groups of workers and to the confidence of workers in their organisation's capacity to keep them safe. Drawing upon case-studies in eight key sectors, the project, supported by the HSE and a range of trade unions, aims to explore the balance between productivity, public health and worker health and safety during pandemics, with a focus upon exemplary and future practice.",2020,2021,University of Greenwich,125873.86,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07353,ES/V015265/1,The Economic Linkages of Covid-19 Across Sectors and Regions in the UK,"The COVID-19 pandemic has affected different countries and regions differently both in the severity and the number of cases. Therefore, different regions within countries may require different policies to effectively address the Covid-19 epidemic and minimize its socio-economic impact. The project wants to understand these asymmetries and help the design of policies that can be effective in restarting the economy and encouraging recovery and long-run renewal at the regional and sectoral levels. To achieve this goal, I plan to study the spatial dynamics of COVID-19 employing an epidemiological model embedded in a quantitative multi-sector economic spatial framework that includes trade in intermediate products. My research focuses on the regions of the UK and incorporates their main international trade partners such as the surrounding European nations, the US and China. The main hypothesis is that economic links among locations work as vectors for the disease and are, therefore, another very important factor for its spread. Specific questions that I want to answer include the following: How does the infection spread over time and space as a result of economic interactions? How can the pandemic affect inter-sectoral flows and supply-chain links across regions? What can be the socio-economic impacts of alternative policy responses to the pandemic? How can this impact be affected by the industrial composition of regions, the supply-chain links and Brexit? The findings of the project can, for example, help allocate more efficiently the Local Growth Fund across industries by the Local Enterprise Partnership (LEP) Network under the current circumstances.",2020,-99,University of Hull,41986.77,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Economic impacts, +C07354,ES/V015257/1,Feeding the Nation: Seasonal Migrant Workers and Food Security during COVID-19 Pandemic,"he UK edible horticulture sector relies on seasonal workers to plant, harvest and pack crops. 94% of seasonal workers in the UK are EU nationals. Travel restrictions and quarantines pose unprecedented challenges to recruitment, yet seasonal workers remain essential to ensure food security throughout the pandemic. This project examines the recruitment and experiences of seasonal agricultural migrant workers throughout harvest seasons 2020 and 2021. Using 212 remote qualitative interviews and data analysis, findings will support policy interventions from our policy impact partner - the Department of Environment, Food and Rural Affairs - and other stakeholders for which we will prepare monthly reports including comparative international analysis. Furthermore, we will co-produce with our charity impact partner - New Europeans - information materials adapted to the needs of seasonal migrants. To engage with the wider audiences and inform public views about seasonal migration, we propose a web-based Monitor and a virtual exhibition. The project has 6 key objectives: (1) to provide information in real time on worker recruitment and retention in order to support evidence-based rapid interventions and mitigate risks for UK the food supply; (2) to provide information to limit contagion on farms; (3) to document the experiences of seasonal workers and farmers; (4) to inform decisions on the post-Brexit immigration system in light of possible future pandemics; (5) conceptually, to contribute to theories about the high demand for migrant labour in periods of high unemployment and (6) and to debates on the contributions of low skilled migrants as key workers.",2020,2022,University of Leeds,327582.99,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C07355,ES/V015222/1,Mind the Gap: Educational Inequalities during Covid-19,"School closures have affected roughly 10m children and young people across the UK, interrupting their learning and placing considerably more responsibility for educational activities on the home environment than ever before. This is expected to slow the progress of a whole generation of students and to widen gender, socio-economic, and ethnic inequalities. Addressing widening inequalities is essential to avoid undesirable long-term consequences, including negative labour market and health outcomes leading to lower economic productivity, increased health care costs, and reduced social mobility. This research project will analyse the effects of the Covid-19 pandemic on educational outcomes with a view to understanding whether some groups of students have been more negatively affected than others, including by students' gender, socio-economic background and ethnicity. We will consider how the period of school closures has impacted students' learning inputs, comprising investments of time and resources provided by schools, parents, and the students themselves, and how the attainment of year 10 and year 13 students (and higher education participation of A-level students) has been affected by the move to teacher-assessed grades.",2020,2022,University of Essex,148285.69,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C07356,ES/V015206/1,Establishing the impact of COVID-19 on the health of domiciliary care workers in Wales: developing a model for UK service planning and carer support,"Domiciliary Care Workers (DCWs) are employed in both public and private sectors to support adults at home. The support they provide varies but often includes personal care, which demands close contact between care worker and the person being supported. Since the start of the COVID-19 pandemic, people working across the care sectors in England and Wales have experienced higher rates of death involving COVID-19 infection. Social care workers, in both residential and domiciliary care settings, have been particularly badly affected, with rates of death involving COVID-19 approximately double that for health care workers. We do not fully understand the full impact on domiciliary care worker mortality, how COVID-19 has affected worker health more broadly, and the risk factors which contribute to these. Existing evidence on deaths from the ONS relies on occupational classification. However, for many individuals reported as dying with some COVID-19 involvement, information on occupation is missing (18% and 40% missing for males and females respectively). The impact of COVID-19 on the health of domiciliary care workers (DCWs) is therefore likely to be considerable, including on COVID-19 infection itself, mental health, and respiratory illnesses. We aim to generate rapid high-quality evidence based on the views of care workers and by linking care workers' registration data to routine health data. We can use this information to inform public health interventions for safer working practice and additional support for care workers. Our study will use a combination of research methods. We will use existing administrative data involving carer professional registration records as well as health care records. Our analysis of these data will be guided in part by qualitative interviews that we will conduct with domiciliary care workers in Wales. The interviews will address the experiences of care workers during the course of the pandemic. Registration data for care workers in Wales will be securely transferred from the regulatory body, Social Care Wales (SCW) to the Secured Anonymised Information Linkage (SAIL) Databank at Swansea University. These data will be combined with anonymised health records made available from the SAIL databank. Information which could be used to identify individual care workers will be removed in this process. We expect that this will create a research database of all domiciliary care workers in Wales, approximately 17,000 individuals. From this group we will also identify about 30 care workers to be approached via SCW to take part in a qualitative interview. The interview sample will be chosen so that it includes workers from a variety of backgrounds. In our analysis, we will describe the socio-demographic characteristics of the group of care workers in the research database, for example, their average age. We will establish the number of care workers with both suspected and confirmed COVID-19 infection. Will explore how infection with COVID-19 has impacted on key health outcomes, including whether workers were admitted to hospital or died. We will also explore the health of care workers before and during COVID-19 pandemic. We will use the information gained from interviews with care workers to guide the way we analyse the health records of the care workers. Finally, we will examine how well the results from our analysis of care workers in Wales can be used inform what may be happening for workers in other countries in the UK. To ensure that our findings will be of most use to those working in social care, we will work with an Implementation Reference Group. The group will include key stakeholders such as representatives from regulators from across the UK. Working with this group, we will provide rapid recommendations to drive public health initiatives for care worker safety. This may include changes in working p",2020,2022,Cardiff University,441199.57,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07357,ES/V015141/1,"Responding to the needs of refugees and asylum seekers in the context of Covid19 - resilience, adaptation, and new forms of care","This project explores the needs of refugees and asylum-seekers in Glasgow, Scotland and in Newcastle-Gateshead, in the North-East of England, in the context of COVID-19. We focus on these cities because they are key points of dispersal with established asylum service infrastructures spanning distinctive national contexts. We will investigate and compare both the response of organisations who provide services for refugees and asylum-seekers, as well as the lived experiences of refugees and asylum-seekers in the context of a global pandemic in Scotland and England. This will build upon five pilot interviews undertaken with refugees in Newcastle-Gateshead during the COVID-19 pandemic. This will facilitate a cross-national, cross-city account of the lived resilience, adaptation strategies and new forms of care that have emerged in the two cities, that can inform local and national government policy. A UK wide survey will provide a crucial overview of the impact of COVID-19 on asylum-seekers and on asylum services. This will be conducted as the start of the study and again six months after this in order to assess how the sector is responding to the unfolding situation. Twenty interviews with organisations who provide services for refugees and asylum-seekers (10 in each city) will supplement forty interviews with refugees and asylum-seekers (20 in each city). Outputs from this project include three academic journal articles; two research reports and two linked policy workshops/webinars in Westminster and Holyrood; two plain language open access online articles about the research findings; and an animated video.",2020,2022,Newcastle University,345036.58,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C07358,ES/V015117/1,Investigating the monetisation of live streams of musical performances in the wake of COVID-19,"Live performances are a vital income source for over 80% of musicians. The COVID19 lockdown has put a temporary stop to performances in concert venues, while social distancing measures are likely to restrict audiences for months to come, with regular attenders deciding to stay at home and venues having to reduce capacity to adhere to government regulations. The result is a severe loss of income for musicians. Lockdown has seen a number of classical and jazz musicians turn to streaming performances live from their homes. However, while having the potential to make up for loss of earnings from other sources, these live streams are rarely being monetised. COVID19 has the potential to be the catalyst for 'creative destruction', bringing into question traditional music industry business models while offering new ones. This research project will investigate optimum ways of monetising live streamed performances. The outcome of the research is an Open Access report for classical and jazz musicians, featuring best practice guidelines and focusing on the staging of virtual concerts; technical requirements; streaming platforms; methods of generating income; collaborations with venues; and online audience engagement. This will enable musicians to quickly and effectively access new income streams. Key findings from the report will be disseminated to over 50,000 UK musicians by the project's partner organisations, including the Musicians' Union, the Incorporated Society of Musicians, and the Music Venue Trust, while the full report will be downloadable from a project-specific website.",2020,-99,Middlesex University London,67082.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07359,ES/V01367X/1,The impact of COVID-19 related school closures on foundation skills in reception children.,"When primary school children return in the Autumn, they will have missed more than a term of usual school provision. The disruption may exacerbate existing inequalities in academic attainment, and potentially create new ones. This project focuses on the impact of school closures on pupils who are at the important transition point between reception and Year 1. In reception, through adult-led instruction, children learn literacy, maths, and language skills that provide the foundation for later academic success. Instruction during the school closure period has varied considerably and inequalities in children's learning experiences during the COVID-19 school closures are evident. These include disparities in the support and resources provided by schools (more active forms of support in advantaged areas), access to technology and study space (more limited for disadvantaged families), and the extent to which parents have been able to support their children. Teachers have reported IT problems, difficulty providing usual standards of teaching remotely, and lower engagement in less advantaged children. As a consequence children are now likely to be on different developmental pathways. For some, progress may have maintained or even accelerated, but for others, progress may have stalled and previously learned skills may have been lost. We urgently need to be able to identify those children whose learning has been most affected by school closures and to better understand the factors that predict poor rates of progress. The usual end of reception EYFS profile has not been completed for this cohort, leaving Year 1 practitioners with limited information to inform support decisions. It is vital that these data are collected as soon as possible. If pupils are unable to recover their rates of learning and secure the foundation skills needed for accessing the school curriculum, then the consequences for their long-term educational outcomes are potentially very serious. In order to provide more differentiated forms of support remotely, in the event of future closures, schools need knowledge of who is likely to be at risk of experiencing the greatest disruption to their learning. Using data collected by schools before closures, at the start of the Autumn term and later in the spring term, we will investigate the factors that have moderated and mediated pupil progress in the Early Years Foundation Stage Profile (EYFSP) goals and reading levels. A large, superdiverse city will serve as the research site to ensure that findings can be generalised to the national context. The data will immediately benefit schools in deciding how to allocate catch-up support. We will convey project findings to policy makers and third sector organisations to inform national strategies aimed at remediating the negative impacts of lockdown post-COVID-19 and addressing inequalities in the event of future school closures.",2020,2021,University of Leeds,201689.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C07360,ES/V013203/1,The impact of COVID-19 on the provision of Early Years childcare in England and Wales,"Early Years (EY) childcare is critical to the UK economy and society given its positive impact on child development and wellbeing. Without the provision of formal and informal childcare, parents will not be able to return to work during or after the COVID-19 crisis, which will exacerbate intra- and inter-household inequalities. This will be includes notably gender inequalities given women's working-lives are impacted most by the absence of EY and informal childcare through families and friendship networks. The urgent challenges that this research will address in the context of COVID-19 are in relation to: 1) Disruption to and sustainability of provision Formal childcare faced financial difficulties before COVID-19 (Penn et al 2011) and 1 in 4 nurseries said that they may not reopen after the crisis (EYA 2020). It is critical to generate empirical evidence on why and where these closures are occurring, what closures will mean for families, how the changing EY landscape and its sustainability will impact on returns to work and gender and socio-economic (in)equalities. Additionally, it is essential to understand the impact on home-based and informal care. Pre-COVID-19, thousands of nannies and childminders and five million grandparents regularly provided childcare. We will generate knowledge of their ability to provide care, as well as parental responses to loss of informal support and the implications for EY provision. 2) Ensuring safe environments for workers, children and families. Childcare necessitates close physical proximity. Some social distancing and safety measures have been enacted, but better understandings are needed of the challenges this poses for providing safe EY environments, and the additional financial pressures it brings. There is an urgent need to understand how staff, children and families who are clinically vulnerable, and may not be able to return to group settings can be supported. The research seeks to find out: - What are the key pressures on EY childcare provision as a result of COVID-19? - How will the landscape of formal and informal childcare provision change during and after COVID-19? - How can sufficient provision be ensured and made sustainable and safe for providers, staff and families? - How can a more sustainable future for the EY childcare sector be created? This project will respond to these questions and challenges via four Work Packages (WPs): WP1: Nursery and pre-school group providers. A survey of 1000 nurseries over two waves complemented by qualitative interviews with 25 nursery managers and 50 nursery workers across two waves to capture change over time. WP2: Home-based childcare workers: A survey of 500 nannies and 500 childminders plus qualitative interviews with 25 nannies and 25 childminders over the same two waves. WP3: Parents and grandparents: A survey of up to 1000 parents of children aged 0-4 years old, over two waves complemented by qualitative interviews with 25 parents and 25 grandparents who provide at least one day of childcare pre COVID-19 for 0-4 year-olds. WP4: Case studies of four different countries, 2-4 expert interviews with key stakeholders in EY childcare provision, to explore best practice in other contexts and draw lessons for developing policy in the UK. This project will be the first to generate detailed, longitudinal evidence on the immediate and longer-term impacts that COVID-19 has on different types of formal and informal childcare provision across England and Wales. The evidence generated will provide urgently needed insight into the challenges of delivering sustainable childcare in the UK following COVID-19 and potential impact of loss of both formal and informal provision of care.",2020,2022,University of Leeds,470817.34,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C07361,ES/V016970/1,The impact of COVID-19 on unemployment and earnings inequality,"The UK Government has recently announced a set of policies to encourage individuals to retrain and reallocate away from sectors hard-hit by the COVID19 pandemic. Evidence shows, however, that the degree of occupational/industry mobility falls during recessions (see e.g. Carrillo-Tudela, Hobijn, She and Visschers, European Economic Review, 2016). This cast doubts on whether individuals will actually be willing and/or able to change occupations in this difficult time. Our project therefore evaluates how effective different labour market policies are at reducing the impact of the pandemic on unemployment and earnings inequality. We will first document how individuals search for jobs across occupations/industries. For this purpose, we will use newly collected longitudinal data on job search available through the Understanding Society COVID19 study. Informed by these data, we will develop and structurally estimate multi-sector business cycle models with heterogenous agents in which workers' occupation/industry mobility decisions trade off idiosyncratic career prospects against the relative abundance of vacancies across sectors. This framework will allow us to quantify the effectiveness of e.g. job seekers assistance, re-training and job retention schemes on unemployment and inequality through their effects on workers' reallocation and firms' layoff and job creation decisions. To showcase our findings, in addition to academic articles we will make freely available an ""unemployment and inequality calculator"". This will provide the likely evolution of unemployment and earnings inequality under different simulated policy regimes. Users will be able to evaluate a combination of these policies by simply changing the parameters that describe them in the models.",2020,-99,University of Essex,313141.85,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07362,ES/V017055/1,"Locked down, locked out? Local partnership resilience in the COVID-19 pandemic","While its long-term economic and social effects are unknown, Covid-19 has created both challenges and opportunities for reducing social deprivation. Local partnerships have a key role in addressing social inequalities, particularly in Scotland, yet little is known about these partnerships and their adaptations to the pandemic. Investigating this would allow new and innovative responses to be identified and promoted, to mitigate the impact of Covid-19 and other crises on the most disadvantaged groups. This project will be undertaken in Scotland to provide evidence to local partners across the UK, as well as contributing to academic knowledge about local governance, partnerships, community resilience and social impacts of Covid-19. Scotland's local partnership approach, developed in response to austerity in 2011, aims to improve efficiency and reduce inequalities by prioritising partnership and prevention (Christie Commission, 2011). The pandemic may have hindered physical face-to-face 'partnership work' which depends on regular meetings and local support agreements; however, there is evidence that some local partnerships have overcome bureaucratic obstacles and inter-agency barriers with unprecedented speed to facilitate partnership working in other ways (Teixeira, 2020). This project will deploy surveys and interviews with local partners across Scotland, providing deep and broad understanding of challenges and adaptations for local partnerships in various settings. Good/innovative partnership practice will be identified to mitigate the pandemic's effects on existing social inequalities, culminating in the dissemination of a Best Practice Framework to stakeholders UK-wide. If funded, this project would begin in November 2020, to share this framework by the end of 2021.",2020,-99,Edinburgh Napier University,43058.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C07363,ES/V017063/1,Counting the costs of COVID-19 on professional football clubs and their communities,"Many professional football clubs, particularly in the lower leagues of English football, are facing financial ruin and on the brink of collapse. This situation is likely to be exacerbated in the coming months owing to the current COVID-19 global pandemic. We have previously argued that football needs to revisit its governance structure to alleviate pressure on lower league clubs by reducing the financial gap between leagues (see Wilson, Ramchandani & Plumley, 2018). Consequently, this project aims to analyse the financial impact of COVID-19 on professional football clubs in England and the wider impact on their communities. In the last year, one community has already lost its professional football club (Bury FC) and other communities have been affected by the demise of semi-professional clubs (e.g. Rhyl FC). The project has three main research questions. First, what is the financial impact of COVID-19 on the professional football clubs? Second, what is the wider economic impact to the local community that a club is placed in given the distinct possibility of matches being played behind closed doors for a considerable amount of time? Thirdly, what are the wider effects on the community in football community trusts and social cohesion? The main aim of this study is to work with professional football clubs and their immediate communities (specifically in League 1 and League 2 of English football) in order to analyse the current financial situation and examine the wider economic impact to the local community.",2020,-99,Sheffield Hallam University,52017.63,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C07364,ES/V01711X/1,"The impact of COVID-19 fear: evidence to inform social, health and economic recovery (a Healthy Ageing In Scotland study)","COVID-19 fear influences decisions such as visiting family and friends, attending GP/hospital appointments, returning to the workplace and employment/consumption patterns. Yet there is no generally accepted instrument to define or measure COVID-19 Fear. This study addresses the problem by: (1) constructing a robust and evidence-based survey instrument for COVID-19 Fear; (2) using the instrument to measure prevalence among older people in Scotland, and (3) relating this to willingness to re-engage across social, health, and economic domains as society adjusts to what may be termed the 'new normal'. This will help researchers and policymakers to understand and respond to the social, health, and economic impacts of COVID-19 fear. The effects of COVID-19 are likely to play out beyond the successful introduction of a vaccine or treatment. So, it is essential that Scotland has the data infrastructure to advance understanding now and in the future. Therefore, we will extend the Healthy Ageing In Scotland (HAGIS, www.hagis.scot) study by partnering with Generation Scotland to advance the development of Scotland's first comprehensive longitudinal study of ageing. Quantitative research will highlight social gradients in COVID-19 fear and will be complemented by qualitative research to address the effects of COVID-19 fear on the use of internet and mobile communication technology (ICT) during lockdown and its impact on social connectedness, engagement with health services, return to the workplace, and consumption and spending patterns. Further an eDelphi exercise will use findings to inform policy and behavioural interventions to address COVID-19 fear.",2020,-99,University of Stirling,773376.38,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Social impacts, +C07365,ES/V017047/1,Developing practical ethics of care for the dead and bereaved: learning from the ways COVID-19 disrupted and reshaped funeral provision,"Funeral provision in the UK was significantly disrupted when COVID-19 infection control policies constrained how and by whom bodies could be attended to and moved to burial/cremation sites; how funeral directors and celebrants could communicate with bereaved families; and possibilities for gathering for funerals, mourning and memorialising activities. The regulations generated significant distress and perceptions of injustice. They also promoted the development of new funeral practices - inviting important questions about funeral provision. Our interdisciplinary research starts from a recognition of funeral provision as a form of care (and set of caring practices) oriented towards people who have died and their bereaved family, friends and communities. It addresses neglected ethical aspects of funeral provision, including, in the context of COVID-19, questions of the fairness and moral dimensions of distress evident in family members' and funeral directors' worries about not fulfilling important responsibilities, or doing wrong, to those who have died or been bereaved. Our ethical analyses will be grounded in an ethnographic examination of changed practices and experiences that includes: (1) analysis of funeral artefacts, including online films, tribute pages, and written accounts; (2 interviews with diverse bereaved family members, funeral directors and celebrants. We will attend carefully to what people consider good and right (or not) and why in different circumstances . We will develop practical ethical analyses of post-death care that address tensions between different purposes of funerals and diverse perspectives on post-death responsibilities. Discussion events with key stakeholders will inform the development of resources for future policy and practice.",2020,-99,University of Aberdeen,516635.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Other secondary impacts, +C07366,NE/V018159/1,Systemic environmental risk analysis for threats to UK recovery from COVID-19,"UK Recovery from COVID-19 needs to balance the needs of the economy, societal cohesion and health. The Environment is not currently explicit in some framings of national recovery, yet there are a number of major risks involving it that can impact economy, societal cohesion and health over a relatively short timeframe (e.g. <24 months). Our team, combining academics embedded in government (Defra) and a leading research centre for evaluating complexity (CECAN), will develop systems analyses to appraise these risks. We will provide knowledge to inform urgent policy to mitigate these risks and recommend monitoring processes that track system dynamics based on key 'watchpoints' to trigger mitigation actions. Furthermore, we will identify uncertainty levels and critical evidence gaps for targeting research. To achieve this, we will use digital workshops with international academic experts and UK government officials to develop causal loop diagrams that map system relationships where environmental risks affect key elements of UK COVID-19 recovery over a short time horizon. We will focus on three important cases: i) Biosecurity- improving resilience to COVID-19 and a second zoonotic emergence; ii) Improving respiratory health of the UK population; iii) Food security- ensuring resilience of home and international supply chains. We will integrate outputs into current Defra-Cabinet Office interactions to ensure that UK strategies for recovery adequately address systemic risks and, more generally, raise the profile of the need to explicitly appraise and mitigate for complex risk in UK governance, especially in the context of rebuilding the nation during COVID-19.",2020,2022,University of Reading,534717.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C07367,NE/V018108/1,Extension of the Breathe-London air quality network into the Covid-19 post-lockdown and recovery periods,"The overarching aim of this proposal is to deliver critical insights into the impacts on air quality following the UK's immediate and medium-term response to the global Coronavirus pandemic using the Breathe-London (BL) air quality network, and to create a unique observational dataset (NO2, NOx, PM and CO2 at 100 London sites) for the next critical periods of the Covid-19 recovery. The urgency stems from the fact that the BL network, which began operation in October 2018, is due to end on July 31st 2020, and the Greater London Authority, due to current constraints, has not yet established a follow-on network. This application responds to the recent decision by the Clean Air Fund (CAF) to extend the operation of the core components of the BL network to the end of November but not the additional network QA/QC or the COVID-19 specific analysis and interpretation activities which are the focus of this proposal (see CAF letter of support). This proposal will exploit this unique opportunity to create a fully validated dataset to the end of April 2021, covering the next phase of the Covid-19 recovery, the recently introduced 2nd lockdown, and the winter and spring period 2020/21. Secondly, it will provide critical additional analysis, including source apportionment and emission index quantification, and data assimilation to improve emission inventories during the recovery phase where unprecedented changes in pollutant sources are occurring. The methodologies and techniques have wide applicability for air quality monitoring, analysis and policy beyond London and would inform similar issues elsewhere in the UK.",2020,2021,University of Cambridge,286740.02,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C07368,NE/V010387/1,"SARS-CoV-2 in Sewage Treatment Works: Environmental Impact, Infectivity and Prevalence Modelling","Given that SARS-CoV-2 RNA is detectable in faeces for prolonged periods (even for otherwise asymptomatic individuals), efforts have so far concentrated on trying to map its prevalence using sewage samples, e.g. via our partners at Bangor University (NERC Urgency Grant NE/V004883/1). Because live viruses have also been detected in the stools of patients affected by COVID19, there is growing concern about the risks of faecal-oral transmission to humans and/or wildlife (where the virus first originated) via sewage outflows and overspill. This is particularly worrying as, for example, hundreds of tonnes of raw sewage enter the Thames each year when sewers overflow during rainstorms, effectively bypassing sewage treatment works (STWs) when they exceed capacity. We combine expertise from Life Sciences and Mathematics at Imperial College, corona virology at Nottingham University, and a network of collaborators to fill this gap and to complement ongoing work in related (but not overlapping) areas. We have also already secured £49K of internal funding from Imperial College to prime the lab work, as a direct in-kind contribution. First, the potential for sewage (via effluent discharge, storm overflows, and other forms of run-off) to contribute to transmission to humans and wildlife will be measured by assessing RNA concentration and viral infectivity from environmental samples, from sewage outflows down to rivers, estuaries, and faeces from wildlife. Second, using data on concentrations of SARS-CoV-2 RNA in sewage and in the environment, we will provide models of population-level prevalence of COVID19 and elucidate key environmental transmission routes for management.",2020,-99,Imperial College London,759407.39,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics | Disease surveillance & mapping, +C07369,BB/V018051/1,Production of full-length proteins of the COVID encounter complex for structural analysis and drug discovery,"The virus SARS-CoV-2 has changed the lives of the world population. The virus is a member of the corona virus family that infects a range of cells in the body, the most important being those of the respiratory tract. The global importance of this disease has led to an extensive effort to develop new therapies that mitigate its effects. One route for developing such therapeutics is to find a way of blocking the entry of the virus into the cells of the host. This process is mediated by a protein on the surface of the virus (Spike) that docks with a protein on the surface of human cells (ACE2). This process is aided by other proteins on the cell surface including one called B0AT1. If this interaction between Spike and ACE2 could be blocked by a drug, then the infection could the inhibited. Unfortunately, all of these proteins a part of a membrane; either the membrane that surrounds the virus or the membrane that surrounds the cell. This makes it technically challenging to make these proteins meaning that is can be difficult to carry out the studies required to produce new drugs. At the Universities of Birmingham and Oxford we have developed 2 novel systems that allow us to make these proteins in a stable form. This enables us to study process of viral binding to human cells in unprecedented detail. In this project we will use these methods to produce each protein and then assemble them to form the structure that triggers viral infection of the cell. We will use Electron Microscopy to study this structure to identify regions that could be targeted by drugs. We will then use the same protein samples to develop systems that could be used to test a wide range of drugs that might inhibit the formation of this complex. Taken together, success in this project could lead to new therapies for SARS-CoV-2 and other corona viruses.",2020,2022,University of Birmingham,569103.01,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +C07370,BB/V01983X/1,An accurate eukaryotic plasma membrane assay for coronavirus binding,"This project focuses on the development of a surface based ACE2 membrane sensor that will provide a highly realistic model of coronavirus cell surface binding and be amenable to high throughput screening. SARS-CoV-2 enters mammalian cells by a transduction pathway whose first stage is the interaction of its spike (S) protein on the viral surface with ACE2 (angiotensin converting enzyme-2), a type-1 transmembrane protein. Once the virus attaches to the membrane surface the S protein is modified by a cell surface protease (TMPRSS2) to form a fusion peptide which inserts into the membrane and facilitates viral transduction. Current S protein/ACE2 interaction studies have primarily focused on utilising a recombinant soluble construct of ACE2 and thus do not truly represent the in vivo processes occurring. Using our expertise with surface based supported bilayers we will fabricate an accurate membrane mimetic of the eukaryotic membrane containing full length ACE2 on a sensor surface. Neutron Reflectometry together with quartz crystal microbalance (QCM) will be used to validate the surface assemblage and viral component binding. The system will then be further developed to include other components known to be involved in ACE2/Coronavirus interaction (e.g. TMPRSS2 & B0AT1), to provide a realistic model of coronavirus membrane surface interaction. This system will be directly translatable to techniques amenable to high throughput screening (QCM and surface plasmon resonance). This will aid the scientific community in studying coronavirus membrane binding and can be used as a diagnostic tool for the identification of inhibitors of coronavirus-membrane interactions.",2020,2021,University of Birmingham,164129.98,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C07371,BB/V017772/1,Exploiting glycosylation against COVID-19,"In this project, we aim to expand our understanding on and exploit the essentiality of protein N-glycosylation for the control of SARS-CoV-2 transmission. N-glycosylation is the most common eukaryotic post-translational modification of proteins; it plays important roles, including protein folding and targeting as well as cell function. All SARS-CoV-2 proteins are predicted to be N-glycosylated, specially the surface homotrimeric Spike protein, which has been confirmed to have 22 N-glycans per monomer and whose structures have been recently determined. It is well known from similar coronaviruses (e.g., SARS-CoV, M-CoV) that surface glycans are important to modulate binding to the host receptor ACE2, and to reduce the accessibility of neutralising antibodies by hindering immunogenic epitopes. Although a lot of information has been obtained on the glycan structures of the Spike protein, to our knowledge, few functional studies on SARS-CoV-2 glycosylation have been performed so far. We hypothesise that interrupting the glycosylation of SARS-CoV-2 and/or host proteins will prevent viral infection and also render the virus more susceptible to the human immune system. We will do this using mainly two approaches: 1) by pharmacological inhibition of the N-glycosylation machinery and 2) by mutagenising specific N-glycan sequons on the virus Spike protein. We intend to translate the generated data into novel glycan-based therapeutics including repurposed glycosylation inhibitors to treat the disease. Our studies may also generate attenuated vaccine strains to prevent COVID-19 transmission.",2020,2022,Liverpool School of Tropical Medicine,246947.75,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Pre-clinical studies",2020 +C07372,BB/V017209/1,A wastewater biosensor enabling detailed COVID-19 population surveillance.,"The UK Government is basing its response to the Covid-19 pandemic on scientific evidence and detailed analysis. For example, the COVID19 National Testing Strategy emphasises the critical importance of robust population-wide surveillance programmes (pillar 4) to understand the rate of infection, and how the virus is spreading across the country. This knowledge directly informs critical decision making and pillar 4 is currently reliant on a recently initiated mass population testing programme using weekly/monthly swab testing of up to 300,000 people. This approach is not only invasive and resource intensive, but it also entirely reliant on public compliance, exceptionally expensive (> £125m per annum on public incentives alone) and measuring <0.5% of the population, offers only limited geographical resolution. In contrast, wastewater surveillance has previously been used to detect and mitigate disease outbreaks and recent research has evidenced that SARS-CoV-2 is excreted into the wastewater system, highlighting an easy to access sample source which could yield real-time geographically detailed population level information of COVID-19 prevalence. RT-PCR analysis of wastewater to detect SARS-CoV-2 is possible in the laboratory, but operating this approach regularly at scale across the UKs network of wastewater sites is exceptionally resource intensive. A simple SARS-CoV-2 wastewater monitoring device that can be used by current site personnel, or incorporated into on-site automated wastewater sampling systems, would offer a cost-effective unparalleled source of detailed data on COVID-19 prevalence. Excitingly, this could provide a robust and enduring real-time warning system of local hot spots, as well as a rich dataset from which geographically specific community-level Governmental policies can be determined, future peaks can be detected early and the effectiveness of a large-scale vaccine delivery and countermeasure programmes monitored. Co-designed with industry partners, this grant aims to prove the concept of a SARS-CoV-2 biosensor as a wastewater monitoring device and demonstrate a simple working prototype operating on real wastewater samples. The ability to rapidly deliver a simple working prototype is supported by the high maturity of the underpinning science (the biosensor system builds on previous BBSRC/EPSRC investment) and the project's direct access to The University of Portsmouth's unique Environmental Technology Field Station (ETFS). The ETFS offers research facilities, wastewater samples and appropriate processing technology at a fully-operational wastewater-works. Industry partners are excited about this work and will be actively engaged in the project, particularly the prototype development stage. They are keen to support rapid exploitation and the envisaged pathway to UK impact as a whole, and the realisation of the full benefit, is through the deployment of ~18,000 SARS-CoV-2 monitoring devices across the UK's network of wastewater sites. Looking to the future, the broader application of the monitoring device is enormous. Not only could it be adapted for use on wastewater systems in less-developed countries, but the biosensor system could be altered to respond to viral mutations or other emerging viral threats. Further work would allow it to be deployed to support wider environmental monitoring applications or as a simple detection/diagnostic tool.",2020,2022,University of Portsmouth,619672.27,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics,2020 +C07373,BB/V01465X/1,Characterisation at the organ level of SARS-CoV-2-induced macrophage-dependent inflammation in the spleen,"This project aims to test if the spleen is a significant source of virus and inflammatory mediators during COVID-19. The induction of a cytokine storm is the cause of pathogenic inflammation both in SARS and COVID-19. Infection of splenic CD169+ macrophages by SARS-CoV-2 has been proposed to contribute to viral spread and excessive inflammation through pro-inflammatory cell death (Park Nat Rev Immunol 2020; Feng BioRxif 2020). Our interdisciplinary team has unique expertise with splenic CD169+ macrophages as key players during systemic infection (Ercoli NatMicrobiol 2018; Chung ALTEX 2019), and with use of a human spleen ex vivo perfusion model that has been authorised for work on COVID-19 (REC 18/EM/0057). We have now confirmed that a subpopulation of human splenic CD169+ tissue macrophages express both the SARS-CoV-2 receptor ACE2 and the spike-modifying protease TMPRSS2. We now propose to exploit our whole organ ex vivo human spleen perfusion model to characterise the steps in the early phases of systemic infection. This set up allows for detailed analysis of the infectious process over time. We will test the hypothesis that these CD169+ tissue macrophages serve as a hub for systemic spread of the virus. The main outputs will be the definition of key events during tissue macrophage infection by SARS-CoV-2 in the spleen. These outputs will provide important insights into the disease process and for optimising systemic host directed treatment strategies.",2020,2022,University of Leicester,418331.55,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C07374,BB/V01384X/1,Development of Broadly Neutralising Antibodies Against SARS-CoV-2,"The beta coronavirus, SARS-CoV-2, has caused a pandemic of unprecedented impact in modern times with nearly 30 million cases worldwide, over 900,000 deaths and immeasurable economic cost. Naturally, there is a huge focus on vaccine development as well as production of monoclonal antibodies as therapeutic agents. Whilst in principle, SARS-CoV-2 is an ideal target for such tools due to its low mutation rate, the very high number of infections worldwide mean the potential for antigenic drift is considerable. Worryingly, mutations arose in the immunodominant epitope within just 2-3 months. This means that there is a real risk new vaccines and monoclonal antibodies will be constantly required. Here, we propose to focus on the ability to efficiently generate broadly neutralising antibodies to develop novel tools to combat the vast majority of virus strains. Broadly neutralising antibodies offer a huge advantage in that they reach normally occluded but highly conserved epitopes that are less prone to mutation. Furthermore, by identifying these epitopes, the targets for next generation, long-lasting, vaccines may be identified. The neutralising activity of the best characterised broadly neutralising antibodies lies entirely within an ultra-long CDR-H3. Here, we propose to perform iterative screening, mutagenesis and selection of a library of naïve ultra-long heavy chain genes, expressed via mammalian cell display. The highest affinity CDR-H3s against the SARS2-CoV-2 spike protein will be selected and characterised. Notably, ultra-long CDR-H3 regions can be transferred to human antibody scaffolds with minimal loss of potency and we propose to generate humanised, broadly neutralising antibodies as novel, long-term therapeutic tools.",2020,2021,University of Leeds,216323.17,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2020 +C07375,BB/V013831/1,Induction and role of type I and III interferons during SARS CoV2 infection,"SARS-CoV-2 infection is a current threat to the world as the cause of the ongoing pandemic. SARS-CoV-2 infects the respiratory tract and spread to the lower airways where an inflammatory response results in the disease COVID-19. We have previously shown that detection of respiratory viruses by pattern recognition receptors drive interferon (IFN) responses that are beneficial for the host response by both inhibiting viral replication and driving an anti-viral inflammatory response. However, if the type I and III IFN response is dyregulated, an enhanced and detrimental lung inflammation can occur. It is very likely that the outcome of SARS-CoV-2 infection, and the magnitude of inflammation, is determined very early during the infection and this will be studied in this proposal. The responses in the lower airways early during infection is impossible to study in humans and therefore, the first part of this work will be to validate several mouse models. We will use humanised ACE2 mice and Adenovirus-delivery of hACE2 to epithelial cells. These models will be transferred to transgenic and knockout mouse models for determination of the induction, timing, source and role of type I and II IFNs in the inflammatory response during SARS-CoV-2 infection. In addition, a SARS-CoV-2 strain will be engineered by reverse genetics, deficient in IFN antagonising genes, that will be used to determine how the virus manipulates the IFN response. Such engineering could eventually contribute to a strategy for attenuated vaccines. In sum, this proposal will unveil a detailed understanding of how the detrimental inflammation during COVID-19 is initiated.",2020,2022,Imperial College London,400203.65,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease models | Disease pathogenesis",2020 +C07376,MR/V038613/1,COVID-19 Modelling Consortium: quantitative epidemiological predictions in response to an evolving pandemic,"Mathematical and statistical modelling has been hugely influential providing rigorous estimates of the COVID-19 epidemic in the UK and making short-term and long-term predictions for decisions on interventions. We are leaving the first phase of this epidemic, cases are slowly declining but there are local outbreaks and variation between regions is of increasing importance. Although standard epidemiological modelling tools have worked well so far, a suite of new tools are now needed that can deal with spatially- and socially-structured stochastic dynamics and population heterogeneities. The teams of epidemiological modellers and statisticians in this consortium represent a core of committed and experienced research groups that have dedicated the last six months to generating predictions, forecasts and insights feeding into SPI-M and SAGE. To tackle the challenges of the next 18 months, these teams require investment in staff time and personnel. The proposed consortium will support these established and collaborating research teams, build national capacity and help train the next generation of applied epidemiological modellers. We have developed a core set of eight overarching questions that we feel underpin the future challenges that will need to be addressed by SPI-M, SAGE & JBC: 1. Data collation, processing and analysis 2. Statistical and computational fundamentals for outbreaks 3. Detection of hotspots or regions in need of greater control 4. Surveillance, Test and Trace 5. Structured environments (workplaces, care homes, hospitals, schools, universities) 6. Realistic individual-scale modelling of contemporary social interactions 7. Implications of finer-scale individual-level characteristics 8. Detailed retrospective analysis of the first wave",2021,2020,University of Warwick,4099240.88,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C07377,MR/V038109/1,Multiresolution predictive dynamics of COVID-19 risk and intervention effects,"SARS-CoV2 is a novel virus, and even as new data improves scientific insight, many uncertainties remain about key aspects of transmission. Throughout the pandemic, mathematical and statistical models of COVID-19 have had an important role in the analysis of epidemiological data, in forecasting incidence trends and in assessing the potential impact of different intervention strategies. Models developed by the Imperial College COVID-19 response team have been particularly influential, but the absence of detailed data on transmission patterns have necessitated important assumptions that limit their predictive performance. This project will (a) extend predictive models of transmission trends to include complex spatiotemporal correlation to better capture new seeding events and improve early identification of hotspots of transmission, (b) understand the causal effect of interventions on transmission and the limits to which this inference is possible, (c) systematically collate and analyse data on transmission in specific contexts (households, schools, workplaces and care homes) to derive specific transmission parameter estimates for those settings to be used to improve the ability of models to predict the impact of targeted non pharmaceutical interventions, (d) Understand how important epidemiological parameters are changing with time and what is driving these changes. This work will directly support the Imperial team's input into the UK COVID-19 response via the SPI-M, NERVTAG and SAGE committees and our partnerships with PHE and the Joint Biosecurity Centre (JBC).",2020,2022,Imperial College London,740359.13,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C07378,MR/V037013/1,Metabolic approaches to abolishing cytokine storm in COVID-19,"Hyperinflammation is a feature of a severe COVID-19 underpinned by dysfunction of mononuclear phagocytes (MNPs). Highly inflammatory blood MNPs traffic to the airways and supplant reparative local MNPs to cause pulmonary damage; similarly, they travel to the heart, kidneys and other tissues. Continuous high levels of multiple cytokines contribute to auto-amplification of inflammation and increased vascular permeability, thrombosis, organ failure and death. The mechanistic determinants of cytokine storm are unknown but intracellular events, such as cellular metabolic adaptation as proposed here, that drive the hyperactivated MNP phenotype offer targets for therapeutic intervention to abolish production of multiple cytokines and provide better outcomes for more patients than mono-cytokine approaches. Recent data from the Thornton laboratory has shown that glucose deprivation of human blood monocytes paradoxically leads to elevated levels of multiple cytokines including interleukin (IL)-6, IL-10 and TNFalpha, i.e. hallmarks of cytokine storm, via increases in oxidative phosphorylation and protein translation. Further metabolic disruption using various metabolic inhibitors, which have counterparts in drugs already in use clinically, induces cell death and abolishes cytokine production. Therefore, we hypothesise that metabolic dysregulation linked to changes in cellular fuel availability underpins hyperinflammation by MNPs and provides a target for therapeutic intervention. To address this, we will use blood and airways MNPs from mechanically ventilated COVID-19 patients to investigate the link between metabolic maladaptation and cytokine hyperproduction. We will then determine if further metabolic disruption, that can be translated clinically by repurposing already approved drugs, might enable elimination of the cytokine storm for patient benefit.",2020,2021,Swansea University,230845.44,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +C07379,MR/V037005/1,AIDED - Acute kIDnEy injury in coviD-19.,"The pandemic caused by the Coronavirus (COVID-19) although primarily affecting the lungs and airways, affects other organs in the body. At least a quarter of people who need hospital treatment for COVID-19 also suffer reduced kidney function (known as acute kidney injury, AKI), which can cause complete kidney failure. As some of the processes that lead to AKI in COVID-19 are specific to the viral infection, it is possible that long term kidney health may be more severely affected. At the moment, we do not know the long-term effects of COVID-19 on the kidneys. Improving our understanding of this is important to allow us to know how best to monitor and support people after their recovery from the initial infection. To address this, we will perform a unique research study that will bring together scientists at the University of Nottingham, UK and those in Uppsala University, Sweden. The study will collect a number of different Magnetic Resonance Imaging (MRI) datasets in ventilated patients with acute COVID-19 in Uppsala University (UU), Sweden. MRI can show the entire kidney in great detail and there is a range of MRI techniques that can assess different aspects of kidney function. Combining the different MRI techniques into a single scan session is called multiparametric MRI. Multiparametric MRI will assess the changes that may have been caused by COVID-19 in the kidneys, such as changes in blood flow, oxygen levels and the degree of scarring (fibrosis). In addition, changes in other organ function such as the liver and spleen will be measured. Importantly, MRI scans do not use radiation (unlike X-Rays and CT scans). Patients scanned at the acute phase of COVID-19 will have their MRI measures collected again at 3 and 12 months after being in hospital. The multiparametric MRI measures collected in Sweden will be analysed by experts at UoN and compared to an existing MRI dataset of non-COVID AKI collected at the UoN, prior to the COVID-19 outbreak, and healthy subjects from both the UoN and UU. These information sources will allow us to understand the long-term effects of COVID-19 on the kidneys. This will inform how COVID-19 is impacting patients' kidney health, and how this should be monitored.",2020,2021,University of Nottingham,133357.77,Human Populations | Other,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,Sweden | United Kingdom,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +C07380,MR/V036998/1,Dissecting innate immune determinants of severity and resolution in a longitudinal study of COVID-19,"The knowledge gap in COVID-19. Myeloid cells have a fundamental role in immune protection against infection. However, their powerful activity against pathogens is usually tightly regulated. This is because when this homeostatic control is deregulated, the over-activated myeloid cells can damage tissues, e.g. resulting in inflammatory joint diseases. Data emerging from the first wave of SARS-CoV-2 infection suggest that the catastrophic tissue damage following coronavirus infection can be attributed to over-activation of myeloid cells, resulting in hospitalisation with respiratory insufficiency and severe COVID-19. There is an urgent need for additional therapeutics to attenuate this progression of severity. With this project, we propose to address important and as-yet unanswered questions about the role of myeloid cells in severe COVID-19. These include: (i) Can we identify characteristics of myeloid cells at an early stage of SARS-CoV-2 infection that might help predict the clinical course of disease? (ii) What allows myeloid cells to escape the homeostatic regulation that would normally attenuate pathology? (iii) Can the regulatory mechanisms be reinstated? (iv) Do myeloid cells retain their aberrant activated state (epigenetics) and contribute to long-term post-COVID-19 symptoms (long-COVID-19)? Experimental plan. To address this knowledge gap, we will investigate the changes in myeloid cells in COVID-19 patients from the day of admission to hospital to post-COVID-19 phase at single cell resolution. Our specific plans include (i) investigating transient changes in their molecular pathways, particularly regulatory mechanisms that should switch-off activation. We will also explore (ii) whether SARS-CoV-2 infection induces long-lasting memory of aberrant activation (epigenetics) in myeloid cells and whether this contributes to long-COVID-19 pathologies. Expectation. We anticipate that our expertise in myeloid cell biology, experienced clinical monitoring and new technologies will discover new mechanisms by which myeloid cells contribute to progression or resolution of COVID-19 disease. From that knowledge we will identify myeloid cell characteristics (biomarkers) that can predict risk of developing severe and/or long COVID-19 and therapeutic targets for new drugs to prevent over-activation of myeloid cells during SARS-CoV-2 infection. The therapeutic potential of these discoveries will be tested in SARS-CoV-2 infected human lung 2D and 3D models in the laboratory. Team. To tackle these challenges, we gathered an international research team of scientists and clinicians with diverse and complementary expertise. These include expertise and facilities in: myeloid cell pathologies (Research into Inflammatory Arthritis Centre Versus Arthritis, RACE, University of Glasgow), COVID-19 (COVID-19 Academic Hospital, Fondazione Gemelli IRCCS, Rome, Italy), SARS-CoV-2 (Centre of Virus Research, University of Glasgow) and epigenetics (Institute of Cancer Sciences, University of Glasgow).",2020,2022,University of Glasgow,635668.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies",2020 +C07381,MR/V036904/1,Exploiting the SARS-CoV-2 nsp14 3′-5′-exoribonuclease as a target for antiviral chemotherapy,"RNA viruses exhibit high mutation rates due to the lack of proof-reading by their RNA-dependent RNA polymerases, imposing a restriction on genome size. In contrast to other positive-strand RNA viruses, coronaviruses have large genomes (~30kb). To ensure high fidelity replication the coronavirus non-structural protein 14 (nsp14) possesses 3'-5'-exoribonuclease (ExoN) activity, which also renders coronaviruses resistant to mutagenic nucleoside analogues (eg ribavirin). Nsp14 ExoN activity is stimulated by nsp10 binding, and structures of the SARS-CoV nsp14:nsp10 complex have been determined to 3.2Å resolution. Importantly, SARS-CoV and SARS-CoV-2 nsp14:nsp10 exhibit 95% amino-acid conservation, allowing us to build a homology model of SARS-CoV-2 nsp14:nsp10. In conjunction with protein dynamic simulations, this model will be subjected to virtual screening to identify small molecules able to bind to either the ExoN active site, or the nsp14:nsp10 interface. Compounds will be tested in combination with mutagenic nucleoside analogues for effects on the replication of SARS-CoV-2, exploiting in-house BSL-3 containment facilities. Specificity and mode of action of compounds will be confirmed by virological and biochemical assays. Our priority is to seek existing clinically approved compounds that inhibit the SARS-CoV-2 ExoN, and could be rapidly repurposed to treat SARS-CoV-2 infection. To this end, we will interrogate the DrugBank database of approved or investigational drugs. This will be followed by an expansion of virtual screening to an in-house library, and a ZINC library subset, comprising available drug-like compounds. In the longer term these could lead to early-stage drug discovery to provide further therapeutic options for SARS-CoV-2, or other future emerging coronaviruses.",2020,2022,University of Leeds,303011.24,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Pre-clinical studies",2020 +C07382,MR/V036750/1,How does SARS CoV-2 infect blood vessels?,"People who are severely affected by COVID-19 show symptoms of damage to their blood system, as well as to their lungs. For example, their blood may form lots of clots, which can cause damage to lots of different tissues in the body. Also other tissues than the lungs may be damaged in COVID-19, such as the heart, and it is likely that infection spreads to these tissues through the blood system. It will be important to know how blood vessels are infected by SARS CoV-2, the virus that causes COVID-19, to understand how damage to blood vessels and other tissues occurs. Our research will discover which types of cells in blood vessels become infected with SARS CoV-2, which will help us understand how blood vessels and other tissues become damaged in COVID-19, and suggest which cells to target to prevent this damage. The two most likely cells that might be infected are endothelial cells, which form the inside surface of blood vessels, or pericytes, which form part of the outer wall of very small blood vessels. In our work, we will use a special inactive version of SARS CoV-2 that cannot replicate but will label cells that have taken it up (become infected). We will apply this inactive version of the SARS CoV-2 virus to endothelial cells and pericytes that are grown in a dish, and see which cell type becomes most strongly labelled, indicating that it takes up the virus most strongly. We then want to find out whether the blood vessels are differently infected in different organs, and whether this could explain some of the non-respiratory symptoms that people suffer from. To investigate this, we will use mice. However, SARS CoV-2 does not infect mouse cells, so we will use two approaches. In one set of experiments, we will use genetically altered mice that express the human version of the protein that binds SARS CoV-2. In another set of experiments we will use normal mice and a version of the inactive virus that has a mutation so it binds to the mouse version of the SARS CoV-2 receptor protein. By injecting the inactive virus into the bloodstream of these mice, we will discover which cells the virus infects in different tissues, including the heart and brain. Finally, we want to find out what factors affect the severity of infection with SARS CoV-2. We will test whether existing inflammation makes it easier for SARS CoV-2 to infect blood vessels, by injecting mice with a bacterial protein that triggers an inflammatory response, before injecting the inactive SARS CoV-2 virus. We will also test whether a gene called APOE4, that seems to be linked with severe COVID-19 in humans, increases infection of blood vessels in our experimental mice. Together, our experiments will discover how blood vessels become infected with SARS CoV-2, indicating which cells to target with treatments, and will test whether risk factors for severe COVID-19 illness could act by increasing the ability of SARS CoV-2 to infect cells on blood vessels.",2020,2022,University of Sussex,314056.89,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C07383,MR/V035851/1,Detection and sequencing of SARS-CoV-2 derived HLA-I bound antigenic peptides in the blood of COVID-19 patients: mapping the CD8 T cell response.,"The immune response to SARS-CoV-2 will comprise both an antibody response (which it is obviously hoped will provide both immediate protection and also prolonged memory) but also crucially a killer T cell response. These cells can seek out and kill virus infected cells, whilst leaving nearby uninfected cells unharmed. Thus they remove the seat of the infection, which antibodies cannot do, and prevent the release of new virus particles. These killer T cells work by recognising small fragments of viral proteins presented to them on immune molecules called HLA class I molecules (HLA-I). Understanding which bits of the virus are being presented by HLA-I to the killer T cells will help inform upon future vaccine design, by incorporating the most targeted bits of the virus into the prospective vaccine. At present this information is not known. We have developed a new method to identify these viral fragments using simple to access blood samples from patients, thus vastly improving on traditional methods which would require a solid lung tissue biopsy. Blood samples contain HLA-I molecules in both a soluble form and also expressed on small vesicles, released from cells in the body, including virus infected cells. Both of these are frequently raised in diseased states where inflammation is present. We will use an antibody that recognises HLA-I molecules to isolate them from patient blood (after first safely inactivating any virus in the blood samples). The small virus fragments are then released from the HLA-I molecules and analysed by a highly sensitive technique called mass spectrometry, which allows us to determine the protein sequence of the virus fragment. Using this technique we can build a picture of which bits of the virus are being seen by these key killer T cells of the immune system. Also, because there are many thousands of different HLA-I molecules present in the human population, our system allows us to identify data which is relevant across a wide spectrum of the population. Our data will allow future vaccine design to incorporate the most relevant bits of the SARS-CoV-2 virus to promote optimal immune responses with, hopefully, long term protection being generated.",2020,2022,University of St Andrews,330665.93,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07384,MR/V03541X/1,Comprehensive Tool Development for the National Covid-19 Effort,"In order to accelerate and facilitate the National efforts in the fight against Covid-19, we are generating an extensive portfolio of Covid related reagents. These cover all components of the Covid-19 virus and some key components of SARs and MERs, including >100 DNA clones, >50 proteins and 42 antibodies. We are making these reagents available globally in the fight against Covid via a new website we have created. https://mrcppu-covid.bio/. The antibodies have been generated in collaboration with CVR, Glasgow and are ovine based polyclonal. These are being fully quality assessed for their utility in immunoprecipitation, western blot and imaging applications. Antigens and being developed with multiple tags and with all relevant variants and DNA clones to cover multiple expression systems and applications. To our knowledge, we are the first to have achieved this complete catalogue of Covid-19 reagents. This project was undertaken within our MRC PPU Reagents and Services Division, which is normally supported only by the income it generates from the cost recovery systems we have put in place. We are also using these tools in our Units research efforts, including screening for modulators of viral proteases and helicases, developing lateral flow and array diagnostic tests, studying the ligases involved in pathogenesis and looking at the interactions of Furan protease and its role in infection. It is crucial for the continued survival of our MRC PPU Reagents and Services operations that we receive some funding contribution for the efforts we are undertaking. We proceeded in the development of the Covid-19 toolbox before securing funding because it was equally crucial to not delay with this project that promises to accelerate the National Covid-19 effort.",2020,2021,University of Dundee,268154.6,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07385,MR/V030841/1,REACT-GE: Multi-omics to identify biological pathways underlying severity of SARS-CoV-2 infection.,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 is a new infectious disease responsible for a global pandemic and presenting major knowledge gaps with respect to disease susceptibility, severity of infection and disease mechanisms. While most individuals infected with SARS-CoV-2 virus are asymptomatic or mildly affected, a minority require hospitalisation, need assisted ventilation and some progress to respiratory or other organ failure/death. The mechanisms for these differences in susceptibility and severity of disease are unknown, but are likely to encompass a combination of genetic susceptibility and gene-environment interactions that lead to downstream biochemical disturbances. We have assembled a multi-disciplinary international team of leading researchers to address these knowledge gaps by applying a multi-omics approach encompassing whole genome sequencing (WGS), proteomic, transcriptomic and metabolomic analyses to mild/asymptomatic cases. We will delineate biological pathways that are protective of or deleterious to the response to SARS-CoV-2 infection that may identify novel targets for treatment and ultimately prevention of the disease (e.g. vaccine response). The partnership between REal-time Assessment of Community Transmission (REACT) and Genomics England (REACT-GE) brings together the DHSC-funded GenOMICC programme and the community-wide viral antigen and seroprevalence surveillance (REACT) platform identifying mild/asymptomatic SARS-CoV-2 positive people in the population. We propose that c.8000 mild/asymptomatic participants are recruited through the REACT study for which we will obtain a multi-omic resource to sit alongside WGS already funded, and thus enhance the biological richness and utility of the resource for drug target discovery. Specifically we propose to undertake a series of proteomics, transcriptomics and metabolomics analyses alongside WGS to provide an unparalleled resource for multiomic phenotyping and discovery.",2020,2022,Imperial College London,2827030.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies | Prophylactic use of treatments",2020 +C07386,MC_PC_20028,Excess mortality during the COVID-19 pandemic in The Gambia: a denominator based analysis within the HDSSs,"The COVID-19 pandemic is causing an unprecedented global burden of mortality. Mathematical models predicted that most West African countries, one of the poorest regions in the world, would exceed 100,000 COVID-19 cases by June 2020. As a result, most countries reacted pragmatically closing borders after the first few cases were confirmed.Official number of COVID-19 cases in Africa show that the expectation has been unmet leading to the idea that COVID-19 severity is disproportionally lower in the continent. The effect of the COVID-19 pandemic, however, goes beyond the official number of cases and deaths. On the one hand, COVID-19 testing is insufficient and, therefore, cases underestimated. Also, limited health resources available are being allocated to the CVODI-19 response which compromises further other health services. Behaviour of people towards health systems may have also changed due to fear of the pandemic.The Gambia, a small West Africa country (2.2 million inhabitants), has 3,626 cases confirmed (September 21st) and 108 deaths. Approximately two thirds of these deaths have occurred in the community and the testing was conducted post-mortem. The MRCG @ LSHTM has 20% of the population under surveillance as part of the Health & Demographic Surveillance Systems (HDSSs). We propose to utilize our HDSSs to assess the excess mortality during COVID-19. To differentiate between the direct and the indirect excess deaths and explain the observed results, we are planning to: (i) conduct analysis of mortality stratified by age group, (ii) perform verbal autopsies to identify causes of death; (iii) carry out COVID-19 serological surveys and correlate hot spots with increased mortality. Rationale: In many high income countries, COVID-19 excess mortality is being quantified showing that the global harm of the epidemic expands beyond the official number of COVID deaths. The overall effect of the COVID-19 in West Africa is unknown. COVID-19 mortality, direct and indirect, is difficult to quantify in this region as there are no official death's register. We rely on official numbers of COVID-19 deaths but, with the limited testing, cases and associated deaths may be largely un-diagnosed. Deaths mostly occur outside of health facilities a situation that may worsen should health systems become overwhelmed. Un-resourced health systems are less resilient to increased burden and therefore, the risk of collateral damage becomes exacerbated.As highlighted by the WHO, community-based surveillance is critical to have a holistic picture of the COVID-19 deaths in economically constraint regions. The HDSS is a unique resource to quantify excess mortality in African countries. Because The Gambia is a small country, we can have as much as 20% of its population under demographic surveillance which will give a robust picture of the overall effect of COVID-19 in the country. We have the opportunity to quantify direct and indirect effects, and identify their drivers. The strength of this study, in addition, is the combination of historical and prospective data and the serology component. https://www.worldometers.info/coronavirus/country/gambia/ https://ourworldindata.org/excess-mortality-covid",2020,2023,London School of Hygiene & Tropical Medicine,391617.17,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Gambia,Epidemiological studies,Disease transmission dynamics,2020 +C07387,MC_PC_20027,COVID-19 in university settings: Establishing an advanced research platform to inform control and mitigation strategies,"Universities have been identified as potential high risk setting for SARS2 spread. This viewpoint is based on specific environmental and social factors - for example mass mobilisation, communal living and frequent social interactions - as well as biological determinants, such as asymptomatic or paucisymptomatic spread. However, the evidence-base is lacking. This project will provide an immediate and timely snapshot of SARS2 prevalence, its molecular epidemiology and seroprevalence in a large cohort (~6K) of hall-based students and associated frontline staff. It will also establish necessary modelling and behavioural research platforms to provide immediate and mid-term analysis of behaviours and social factors associated with infection and spread, as well as its mitigation, with a particular focus on social distancing. It will also utilise existing NIHR-supported activities focussing on the long-term consequences of COVID-19. This will have immediate impact on the national and international higher education community as well as longer-term benefits created through resulting multi-partner collaborative research. These studies will provide important insights into COVID-19, including its epidemiology, control and long-term health impacts.",2020,2020,University of Nottingham,106400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +C07388,MR/V03605X/1,The COVID-19: Clinical Neuroscience Study (COVID-CNS),"Acute neurological complications of COVID-19 affect 20-30% of hospitalised patients, including encephalopathy/delirium, encephalitis, stroke, and Parkinsonism. These are often otherwise unexplained (i.e. excluding risk factors/hypoxia/iatrogenic causes) and often occur in younger patients. Survivors frequently report cognitive impairment,fatigue, and depression. The limited regenerative capacity of the brain means these complications may cause lifelong disability. There is an urgent, unmet need to understand the biological causes of acute neurological complications of COVID-19 and their sequelae. In collaboration with CoroNerve and ISARIC-4C's we have already identified 800 patientswho have been hospitalised with these complications. We will invite these patients to join the COVID-CNS NIHR BioResource, using existing HRA approvals and protocols.We will conduct a case control study to determine the phenotypes and genotypes ofthese patients relative to 500 previously hospitalised controls including those from ISARIC-4C's and PHOSP-COVID (400 with COVID-19; 100 non-COVID). We will collect datafrom clinical cases notes and electronic records, then assess neurological/cognitive/psychiatric sequelae at 3-6 months post-discharge We will analyse brain injury, virologic, and immunological mechanisms in serum and cerebrospinal fluid, and analyse acute MRI's and, at follow up, functional MRI to study the pathophysiology of these complications.By understanding these mechanisms, we will be able to stratify patients into clinical care pathways and into trials using existing and novel therapies. We will apply this knowledge through our WHO-commissioned Task Force (co-Chair Michael) to have immediate impacton patient care and through our PPI programme.The NIHR BioResource will provide sustainability (ALREADY FUNDED) and, through linkage to the community cohort (n=35,000), will allow us to determine if similar, but milder, symptoms are being experienced more widely.",2020,2022,University of Liverpool,1557189.27,Human Populations | Other,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C07389,MR/V03488X/1,CO-CONNECT: COVID - Curated and Open aNalysis aNd rEsearCh plaTform,"CO-CONNECT is a collaborative project and it has four CO-PIs: Jefferson (Dundee), Sheikh (Edinburgh), Hopkins (PHE) and Quinlan (Nottingham).The UK has rich, globally important COVID-19 datasets, including large serology cohort studies funded by UKRI, Wellcome, DHSC/NHS, NIHR and the devolved administrations. However, this breadth of data creates a risk of fragmentation, inconsistent structure and access processes, severely limiting utility, timeliness and impact.Our vision is to transform UK COVID-19 diagnostic datasets to be Findable, Accessible, Interoperable and Reusable (FAIR) and couple this with expert data engineering, enabled by Health Data Research (HDR) UK, to catalyse responsible and trustworthy use of the data for research and innovation.We propose to support PIs and data custodians to link COVID-19 cohort, serology and other health and non-health datasets. This longitudinal linkage is vital to derive new scientific insights and deliver informed decisions about how best to control the spread of SARS-CoV-2. At present there are >30 independent studies with no streamlined approach to linkage to other health and non-health related datasets, lack of data standardisation, and no strategic approach to synthesise analyses across studies.SAGE (9th June) requested HDR to work with partners to develop the UK-wide serology and testing data research asset that is linkable to other data sources.This proposal has been prepared in response to this request. We have bought together 41 leaders from 29 different organisations and 44 data sources to address a major data engineering challenge by building upon existing UKRI investments, including the HDR BREATHE Hub, to create a 'one-stop' service for trustworthy, multi-stakeholder utilisation of curated COVID-19 data for public, private and third sector benefit.",2020,2022,University of Nottingham,2720667.95,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2020 +C07390,MR/V034405/1,Understanding and mitigating the psychosocial impact of the COVID-19 pandemic on NHS staff in England,"The nation has relied heavily on NHS healthcare workers (HCWs) during the COVID-19 pandemic and an effective workforce requires good mental health. Poor quality surveys report high levels of distress in HCWs unconfirmed by some population based studies. So robust evidence is still lacking on the size and impact of the pandemic on HCWs, who is at risk, and what support they may require, if any. We will investigate the psychosocial and occupational outcomes of the pandemic on NHS staff in England, using a well-defined sampling frame across 13 Trusts. Our pilot study, already conducted in three Trusts (Guy's and St Thomas', King's College Hospital, and South London and Maudsley NHS Foundation Trusts) has demonstrated feasibility and acceptability of a brief baseline questionnaire. We request funding to expand the study in time, geography, and depth. The original sample will be followed four and eight months later, with ten new centres contributing data at these timepoints. Questionnaire data will be validated through standardised diagnostic interviews administered by telephone in a sub-sample, to distinguish distress from disorder. Additionally, we will address the use and outcomes of staff support/wellbeing, and a UKRI- funded ethnicity-focused module will capture inequalities in mental health and occupational outcomes. PPI/E will be central: we will establish a steering PPI/E group of NHS workers, unions, and employers, ensuring strong representation of BAME staff. Findings will inform an effective support strategy for NHS staff during and following the pandemic, for example through workforce planning, emergency response strategies, or targeted support. The project team and partners have extensive networks in policy and practice, allowing for rapid dissemination of findings.",2020,2022,King's College London,355207.09,Human Populations,Asian | Black | Other | Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07391,MR/V033530/1,Household Transmission and Immunity to SARS-CoV-2 among Paediatric Clients of a Primary Care Center in a Low-resource Community in Rio de Janeiro,"This project aims to characterise household transmission dynamics in Manguinhos, an urban slum (favela), which has one of the lowest Human Development Index (HDI) scores of Rio de Janeiro/Brazil. We will also estimate the immunity of the study population against SARS-CoV-2. This will be a prospective study of household contacts of laboratory-confirmed SARS-CoV-2 infected and non-infected children and their families, following the WHO Household Transmission Investigation Protocol for COVID-19. We will recruit children 0 to 13 years of age who are brought to the local health care centre to receive free vaccinations. The clinic provides primary care to 4,300 children in this age group per month. After obtaining written informed consent from the child's guardian, samples will be collected at the clinic (oral fluid, nasopharyngeal and rectal swabs, and serum). The child's home will then be visited to collect samples from contacts. All samples will be screened for SARS-CoV-2 by PCR following the Charité protocol, and serum for IgG antibodies by ELISA or CLIA and for neutralising antibodies by FRNT. At the household we will collect samples at Days 1 (first visit), 14 and 28, every three months during the first year and twice in the second year. Clinical follow up will be done through telephone calls and video conferences by nurses and paediatricians from Day 0 to Day 28.",2020,2022,London School of Hygiene & Tropical Medicine,407561.21,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Urban Population/Setting | Other,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas,,,,United Kingdom,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C07392,MR/V030884/1,"African critical care registry network for pandemic surveillance, clinical management and research","Our group of LMIC based co-investigators and project partners from established critical care and pandemic networks aims to address the knowledge gaps that exist regarding the natural history and clinical course of COVID-19 related critical illness in seven African countries. In achieving this aim, we will address operational gaps in pandemic responsiveness by establishing a network with the infrastructure to identify optimal strategies for supportive care and interventions for the same patients.The aim will be achieved by 3 activities. 1. Implementing a setting-adapted (International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Clinical Characterisation Protocol (CCP) compliant critical care registry. The near-real time registry with integrated ISARIC tier 0-2 CCP and capacity for clinical research will be implemented in 35 critical care sites in seven countries building on the methods used in the Wellcome-supported nine country Critical Care Asia (CCA) network. Registry data output will include epidemiology, quality of care processes, risk stratification and outcomes. A comprehensive national service evaluation of critical care services and an EARL evaluation will also be conducted. 2. Identifying stakeholder research priorities to optimise critical care processes and outcomes leveraging activity 1 data. We will facilitate Audit & Feedback workshops and research prioritisation exercises for site stakeholders (inc. public) using Activity 1 output to determine priorities for optimising COVID-19 clinical management and pandemic responsiveness, especially for the critically ill, obstetric and surgical populations. 3. Recruiting sites to registry enabled clinical trials.We will facilitate sites to participate in registry-enabled clinical trials mentored by our group and project partners. The registry infrastructure and specific data will optimise sampling strategies, patient recruitment and study monitoring.",2020,2022,University of Oxford,736778.77,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Clinical characterisation and management | Research on Capacity Strengthening,"Supportive care, processes of care and management | Cross-cutting",2020 +C07393,MR/V030825/1,The DOMINO Study: Measuring and mitigating the indirect effects of COVID-19 on TB and HIV care in Indonesia,"The global health community has made urgent calls for countries to find solutions to minimising the impact of COVID-19 on programs targeting long-standing health problems such as TB and HIV (1). Indonesia, with a population of around a quarter of a billion people, currently has the highest number of COVID-19 infection cases in Southeast Asia, averaging 1000-1300 new infections each day since the 15th June and a case fatality rate of around 6.6% (2). It is also ranked third in TB burden globally (3) and one of a few countries where the number of new HIV infections is rising (4). In recent years Indonesia has strengthened its commitment to controlling these two important diseases. However, the diversion of health resources to the pandemic along with social distancing policies is creating new vulnerabilities and exacerbating existing ones for TB and HIV programs and affected populations. Our team is partnering with the Indonesian government and community organisations to conduct an observational cohort study across all TB and HIV facilities in the major cities of Bandung (N=62) and Yogyakarta (N=30) to assess clinical outcomes before and during the pandemic. We will analyse routinely collected data to measure linkage to care, retention in care and treatment outcomes along TB and HIV cascades of care. Qualitative methods will be used to explore the experiences of TB and HIV patients and their health care providers during the pandemic, including changes to treatment seeking and actions to minimise disruptions. Out-of-pocket health spending by TB and HIV patients and their families during the pandemic will be measured using structured diaries. Wider health system impacts of COVID-19 on stocks of medicines/tests and health facility funding levels will be assessed using facility records and interviews with health authorities and facility staff. Our findings will generate recommendations on how to minimise disruptions to HIV and TB services in the face of the pandemic.",2020,2022,London School of Hygiene & Tropical Medicine,560442.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Western Pacific,,,,United Kingdom,Indonesia,"Secondary impacts of disease, response & control measures | Health Systems Research","Indirect health impacts | Health service delivery | Medicines, vaccines & other technologies",2020 +C07394,MR/V028790/1,Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis (ICECAP),"The current coronavirus pandemic is causing significant illness and death. Severe coronavirus disease 2019 (Covid-19) leads to acute lung damage and organ injury, often requiring intensive care admission and prolonged periods of time on a ventilator. As this disease is new, the way that the virus causes organ injury is not understood. It is therefore urgent and vital that the effects of severe Covid-19 are described to rapidly inform clinical management and identify new treatment approaches. The ICECAP consortium was established as a rapid response to the Covid-19 pandemic. By assembling a team of expert clinicians and scientists we are studying key features of fatal Covid-19. Authorised hospital post-mortem examinations of those who have died from Covid-19 provides a unique opportunity to study the whole body in a level of detail that is not possible during life. By collecting and analysing tissue samples collected during post-mortem examinations this will yield crucial information on the presence of the coronavirus in multiple organs in the body and also understand in greater depth how the body's immune system is responding. This allows us to rapidly answer important clinical questions and help to rapidly inform the evaluation and development of therapeutic interventions for Covid-19.",2020,2021,University of Edinburgh,263995.69,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C07395,MR/V028782/1,"To investigate the spectrum, determinants and long-term outcome of SARS-CoV-2 in African children, immune responses and protective role of prior sHCoV","To prospectively investigate SARS-CoV-2 in African children, we will leverage 2 ongoing cohorts: (i) the Drakenstein Child Health Study (DCHS), a birth cohort study with comprehensive longitudinal measurement of risk factors, a very well phenotyped population and large biobank of samples. Children will be followed for 3 study visits with repeated sampling through the epidemic and at any intercurrent illness. (ii) study of children hospitalized with pneumonia at the largest childrens hospital in Sub-Saharan Africa. Children will be tested for SARS-CoV-2 and for other viral pathogens by PCR of nasal samples.Clinical features, risk factors, nasal specimens and blood samples (serum, Paxgene, PBMCs) will be collected in children. PCR for SARS-CoV-2 and other respiratory viruses will be done on nasal samples. Serology for SARS-CoV-2 will be done in all children; in DCHS we will also investigate the role of prior seasonal coronavirus (sHCoV) infection using biobanked samples to investigate serological responses to sHCoV and potential cross protection for SARS-CoV-2. Immune markers, cytokines and RNA expression profiles will be measured to identify SARS-CoV-2 associated inflammation compared to other viral infections or asymptomatic illness. All children will be followed at 12 months for long-term health outcomes.This study design will enable us to investigate symptomatic and asymptomatic SARS-CoV-2 and serological responses, including cross-reactivity and cross-protection from sHCoV. We will also be able to compare clinical, immunological and inflammatory profiles and long term outcome of children with COVID, with asymptomatic infection, and with other viral-pneumonia, in a LMIC community and hospital setting.",2020,2022,University of Cape Town,566224.89,Human Populations,Unspecified,Children (1 year to 12 years),Other | Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics | Disease pathogenesis",2020 +C07396,MR/V028561/1,Promoting health and safety in traditional food markets to fight COVID-19 in Peru and Bolivia,"Traditional food markets are important for the welfare and livelihoods of thousands of families in low and middle-income countries (LMICs). During the current COVID-19 pandemic, these markets have been identified as important locations for the spread of COVID-19. The establishment of control measures to reduce risk of infection in traditional food markets is an urgent need. However, it is also important that these measures are developed collaboratively with those that may be affected, taking into account the adverse effects that strict controls may have on thousands of families whose lives depend on the markets. In this proposal we build on ongoing projects in two localities of Bolivia and Peru and on requests to members of the research team to support COVID-19 response in these localities, particularly in relation to controls in markets. Our strategy to tackle this complex issue uses research methods from different disciplines such as epidemiology, microbiology and the social sciences. We will provide a program to reduce COVID-19 transmission in food markets applicable to different countries, a computer tool to simulate, in a virtual market, how changing the way the market operates can reduce risk of infection and data on the presence of antibodies and of the virus itself in people at high risk, which could help answer important pending questions about COVID-19 infection. We will also build local capacity of market sellers, regulators and university students, which will be important not only in the current COVID-19 pandemic but to face future public health emergencies.",2020,2022,Royal Veterinary College,535721.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas,,,,United Kingdom,Peru | Bolivia,"Epidemiological studies | Infection prevention and control | Secondary impacts of disease, response & control measures | Health Systems Research",Impact/ effectiveness of control measures | IPC at the human-animal interface | Economic impacts | Health leadership and governance,2020 +C07397,MR/V028545/1,COVID-19 Mapping and Mitigation in Schools (CoMMinS),"This proposal will meet the urgent need for mapping and mitigation of COVID-19 in schools in light of their planned full re-opening in September 2020. Schools pose a major challenge due to features of their operation including the likelihood of cases being asymptomatic[1], the high number of contacts, the presence of vulnerable persons, and the potential for rapid onward transmission to family contacts of children and staff[2,3]. These challenges must be weighed against the benefits to children including resuming their education, peer interaction and social development[3,4]. A deeper understanding of infection history and dynamics and enhanced mitigation measures will have widespread benefit for outbreak control and future pandemic resilience. We will undertake a large-scale mapping study of prior and current COVID-19 infection in pupils and staff, including prospective testing over a 6-month period. This will dramatically enhance our understanding of infection patterns in this age group. Results will be mapped to home postcode location and linked to NHS system-wide data to highlight area-based and individual-level risk factors. To mitigate against infection transmission we will adapt evidence-based digital tools and co-create whole school implementation interventions to support positive infection control practices by staff, parents and pupils. We will co-design and develop a system to collate multiple sources of information to augment contact tracing and facilitate outbreak control. We Zill e[SlRUe Whe iPSacW Rf UeWXUQiQg WR VchRRl fRU VWaff aQd SXSilV¶ PeQWal ZellbeiQg, their attitudes towards actions taken to mitigate the spread of COVID-19, and potential interventions to address identified difficulties.",2020,2022,University of Bristol,1873747.89,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C07398,MR/V028510/1,Enabling Child and Adolescent Mental Health Services (CAMHS) to provide efficient remote treatment for child anxiety problems in the COVID-19 context,"This proposal addresses the need for evaluation of innovations in health and social care delivery prompted by the pandemic which can be generalised and actioned in the pandemic context. Specifically this proposal sets out to mitigate the impact of the COVID19 outbreak on children, families and Child and Adolescent Mental Health Services (CAMHS) by evaluating an innovative, potentially cost-effective, digital intervention for child anxiety problems. The focus is on child anxiety problems because (i) they are the most common mental health problem across the lifespan, (ii) they typically first occur in childhood and are a common reason for referral to CAMHS, (iii) fears, worries, and anxieties have been fuelled by the current context which has increased perceptions of threat and uncertainty, and (iv) CAMHS have identified children with anxiety problems as a key risk group in the context of COVID-19- both during lockdown and as social distancing measures are relaxed. We will conduct a multi-site randomised non-inferiority trial to establish whether a novel online, parent-led cognitive behavior therapy program (OSI; Online Support and Intervention for child anxiety) is as effective as what CAMHS are currently delivering in the COVID-19 context, and whether it brings health-economic benefits. This research has the potential to provide (i) a solution for efficient psychological treatment for child anxiety disorders while social distancing, (ii) an efficient means of treatment delivery to manage the anticipated increase in CAMHS referrals when social distancing measures are relaxed and schools reopen, and will (iii) pave the way for high quality, efficient evaluation and implementation of digital solutions in CAMHS.",2020,2021,University of Oxford,327259.8,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07399,MR/V028472/1,COV0639 - SCAMP-COVID19: a school-based cohort study of COVID-19 secondary impacts on mental health,"COVID-19 poses a significant threat to health. The government-enforced public health measures, including social distancing and closure of schools and businesses, also pose other threats to the health and wellbeing of society and its social and economic infrastructure. The Study of Cognition Adolescents and Mobile Phones (SCAMP) has been studying almost 7000 adolescents (currently aged 15-17) over the past 6 years, from schools across Greater London. It collected detailed information about adolescents' mental health, their use of digital technology, as well as their lifestyle and behaviour, such as sleep and physical activity. We will investigate the impacts of the COVID-19 pandemic and public health measures on adolescent mental health and wellbeing, within the SCAMP study. We will investigate risk factors for mental health problems due to COVID-19 public health measures and their profound disruption to adolescent education and social networks and find out what factors can be changed to boost resilience. This research will investigate questions such as: whether changes in use of digital technology have a positive or negative impact on adolescent mental health; and who is most at-risk of negative outcomes, such as those experiencing more family stress, lack of access to healthy food and outdoor/green space.",2020,2021,Imperial College London,203942.2,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07400,MR/V028464/1,Suppressing SARS-CoV-2 transmission in public spaces through surface engineering,"The exploration of different ways in which the current Covid-19 pandemic can be kept controlled is crucial to enable reopening the society and ensure a flourishing economy. While a successful vaccine would be the ideal way to put a halt on the pandemic, a rapid deployment is not guaranteed, and may not happen for sometime. Short of a vaccine, measures that can prevent spreading the infection are an important alternative. Apart from airborne direct transmission, indirect transmission via surfaces, in particular in public spaces, can play an important role in spreading the disease. We propose the development and identification of routes for easy deployment of surface materials and coatings that can actively inhibit and retard the spread of the virus from an infected person to others via touch surfaces, by deactivating it. This would potentially be a game changer for ""high-traffic"" surfaces in public spaces. We will build on existing knowledge about the antiviral properties of copper, and seek to optimize them.",2020,2021,University of St Andrews,181659.38,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07401,MR/V028456/1,Nosocomial transmission of SARS-CoV-2,"SARS-CoV-2 spreads in many different types of environments including within healthcare settings. Understanding how much transmission happens in hospitals or in the community will aid our ability to control ongoing spread, as well as to improve interventions. By knowing what factors make certain hospitals hotspots of transmission we can limit spread by targeting these factors in particular. Within this project we will use mathematical and statistical techniques to harness the UK wide data on hospital cases to understand how important transission of SARS-CoV-2 in hospitals was to the first ""wave"" of COVID-19 in the UK and what we could do in the face of any future resurgence.",2020,2021,London School of Hygiene & Tropical Medicine,85157.24,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C07402,MR/V028448/1,A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium,"The immune response to SARS-CoV-2 infection is the critical determinant of clinical outcome for patients but although this can suppress virus replication (immunity) it can also cause damage to tissues such as the lung (immunopathology). It is unclear how effective immunity is established or why it damages tissues. Many UK research groups have initiated research and UK-CIC will bring together a consortium of 17 UK centres to coordinate coronavirus immunology research. We will work on 5 questions: -the features of immunity during initial infection and how this relates to clinical outcome of individual patients. SARS-CoV-2 infection triggers an immediate (innate: interferon and white cell) and delayed (adaptive: antibody and cellular) immune response. How these develop and interact is currently unclear but will determine how quickly the infection is cleared. We will study this in patients with mild and severe infection. A number of risk factors for severe Covid-19 infection have been identified including age, gender, obesity and ethnicity. These will be studied in relation to the features of the initial immune response. -how effective immunity is established and maintained to prevent re-infection After infection the immune response develops some 'memory' of the infection and this helps to prevent reinfection. For some infections (e.g. measles) this protection is virtually complete; for others (such as the common cold) this protection is brief. We do not know what the situation will be for SARS-CoV-2. This work will take samples from people in the first year after infection and measure the virus-specific immune response. We will examine the fine details of how the immune system kills the virus and the longevity of this response. We will examine a broad representation of population groups to do this work effectively and compare groups of different ages and backgrounds. -the mechanisms by which the immune system can damage tissue and how this can be stopped In severe or fatal infection the problems arise due to two mechanisms: (1) The virus infects and damages tissue (2) The immune response to the virus can itself damage tissue In this research theme we will investigate the relative importance of these two problems and try to find ways to prevent them. This will involve taking blood and tissue samples from patients with severe disease and also using post mortem tissue. -if immunity to mild 'seasonal' coronaviruses alters the outcome of SARS-CoV-2 infection The term coronavirus was first used in 1965 to describe identification of a common cold virus and these viruses circulate widely in the community. It is thought that the immune response to these viruses may potentially 'cross-react' with the new SARS-CoV-2 coronavirus, perhaps giving some people relative protection against infection. We will investigate this possibility and assess how it might happen. Here we will use blood samples in the laboratory to assess their recognition of both viruses and also see if blood samples frozen down before the Covid-19 pandemic make any response to the new virus. -the details by which the virus 'evades' the immune system and how this could be targeted by new treatments. Viruses can only grow, spread and cause disease if they are able to evade being killed by the immune system. If we can understand how this happens we might be able to develop new drugs that can block this response and allow the virus to take control and eliminate the virus. This work takes place in the laboratory using viral infection studies of cells. UK-CIC will work with other major recent UK investments in Covid-19 biology and represents an essential additional pillar of UK research infrastructure to hasten the control of the pandemic.",2020,2022,University of Birmingham,4357158.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +C07403,MR/V02843X/1,"Self-harm rates, clinical contact and risks of suicide and early death before, during and after the COVID-19 peak: cohort study of linked health data","The COVID-19 pandemic could have a profound impact on suicide. People who have self-harmed, for example by intentionally poisoning or injuring themselves, have particularly high risks of suicide. Therefore, it is important to understand how the pandemic has affected rates of self-harm. So far, information has come from people who have chosen to respond to surveys, rather than from the general population. We aim to find out: - how the pandemic has affected rates of self-harm - likelihood of being prescribed medication for mental illness and being referred for mental health treatment by GPs for patients who have self-harmed - risks of further self-harm and suicide The pandemic has affected people differently so we will examine differences by age group, gender, ethnic group, existing mental or physical illness and social deprivation. This research will use anonymous health records, linked to information on deaths, for around 11 million patients in England. The study will cover the periods before, during and after the peak of the pandemic, including up to August 2020. The findings will be shared rapidly, with key messages communicated on the study's blog. The research team will also host a webinar to share and discuss findings with local and national suicide prevention team and health services.",2020,2021,The University of Manchester,106398.67,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07404,MR/V028413/1,TraCK Transmission of COVID19 in Kids,"COVID-19 can infect children without causing symptoms, meaning that spread of COVID-19 among children has been almost impossible to study. Other infections in the throat like scarlet fever spread rapidly between children, and spread from children to other household members. In contrast, it is thought that children are not major spreaders of COVID-19. Nonetheless, there is evidence that children are just as likely to have been infected with COVID-19 as adults in some communities. If COVID-19 can be spread by children at a level similar to scarlet fever, we may be missing a vital link in preventing wider community spread of COVID-19. Our study will investigate how quickly and efficiently the virus might be spread by schoolchildren, and will include teachers and household contacts. We will investigate how long children can carry 'infectious' virus, and if the virus is present in saliva or the surrounding air. Conversely, if we find that children do not readily transmit the virus at all, our study will be able to provide a high level of reassurance to teachers, parents, and the public. The findings should provide much needed information for modelling and public health guidance.",2020,2022,Imperial College London,225138.41,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +C07405,MR/V028383/1,"Intersections of ethnicity, gender, poverty, and mental health in adolescence in the context of COVID-19","All teenagers are affected by COVID-19 to some extent. Education is severely disrupted, social activities are restricted, and plans are suspended. For many, these changes will produce feelings of worry and low mood. But some groups will be affected more than others. Those from disadvantaged and marginalised backgrounds (e.g., low-income households, minority ethnic groups), and those who were already experiencing mental health difficulties, may be particularly vulnerable. However, at present we have little information about the impact of COVID-19 and school closures on the mental health of adolescents. Without this, it is difficult to develop effective responses to support those who need it most. The proposed work will address this knowledge gap. We will use existing data from, and collect new data in, our ongoing study of adolescent mental health, REACH (www.thereachstudy.com), which - uniquely - involves thousands of teenagers from low income households and minority ethnic groups. Within 12 months, we will (a) generate new information about which groups of young people are most affected and why (b) work with young people, teachers, and the public to translate this information into public health benefits, and (c) consolidate this unique study for further research on lasting impacts of COVID-19 and potential interventions.",2020,2021,King's College London,215440.05,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07406,MR/V028375/1,"Investigating incidence, severity and risk factors for COVID-19 in BAME and Migrant groups to inform public health action.","The severity of illness from COVID-19 and risk of death appears to be increased in minority ethnic and migrant groups. Most of our information about COVID-19 is from people who are ill enough to have to go to hospital. This means we have an incomplete understanding of the infection and how we can tackle it in the community. Our first study will solve this problem by including more minority ethnic and migrant communities in our existing study, Virus Watch, which is studying COVID-19 in the community. Each week we will ask 12,000 people to report any symptoms. We will test a subset any time they have symptoms, and we will perform antibody blood tests (to find evidence of ever having the infection) at the start and end of the study. We will be able to explore why COVID-19 affects BAME and migrant communities differently. Our second study will use health records for nearly all non-EU migrants and refugees that arrived in the UK since 2015. We will use these data to examine how often these groups get diagnosed, hospitalised and die from COVID-19 and investigate whether their existing health conditions and socioeconomic circumstances affect their risk of COVID-19.",2020,2022,University College London,936099.22,Human Populations,Asian | Black | Other | Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C07407,MR/V027956/1,Investigating SARS-CoV-2 Transmission in UK Jewish Communities,"This study, in a UK Jewish community, will investigate the role of children, cross-protection from non-SARS-CoV2 coronaviruses, asymptomatic transmission, household structure, and pre-existing conditions on transmission and burden of disease. This will generate strong evidence for major unknowns in infection natural history, and by using transmission models we can translate findings to improve UK projections of subsequent waves. Uniquely this community has maintained community level records on treatment both within and outside the home for all members providing an unparalleled record of the impact of COVID-19 and combined with their highly-connected population structures and large inter-generational household structures make them an ideal case-study in understanding drivers of transmission in high-risk communities and in particular the role and/or risks associated with children. We will undertake a cross-sectional survey enrolling 500 households. We will collect information on household structure, social mixing, evidence of COVID-19 and collect samples for serological testing for SARS-CoV-2 and HCOV infection. We will collect detailed data on community understanding and perceptions of risk and acceptability and feasibility of future control strategies such as vaccination. We will use these data to fit a mathematical transmission model of SARS-CoV-2 and estimate risk of each transmission in different settings, such as households, schools, synagogues and yeshiva, which is critical as the community (and the country) exit lockdown. By analysing households, we will quantify transmission from children, by comparing the force of infection by household size and composition. This information is critical for re-opening of schools in the Autumn.",2020,2022,London School of Hygiene & Tropical Medicine,167074.6,Human Populations,Other,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Approaches to public health interventions,2020 +C07408,MR/V027883/1,"Transmission, pathogenesis and immunogenicity of SARS-CoV-2 in frontline healthcare workers: a national longitudinal cohort of 1320 participants","We want to know how many and which doctors and nurses have been infected with the virus (SARS-Cov2) that causes COVID-19 with or without symptoms. We have been collecting blood from 1320 healthcare workers on a weekly basis during the pandemic. We are analysing blood for antibodies against the virus. We will continue to measure their blood 10 times up to 6 months after the lockdown is lifted. This study will also allow us to know how the levels of antibodies in blood change over time and which of the antibodies are able to fight the virus. We will investigate whether individual characteristics, including genetics, age, sex, ethnicity, affect the length of time for which antibodies remain in blood at high enough levels to fight the virus. Among the doctors and nurses in our study we have people who have had a severe infection, others who have had mild symptoms and many with no symptoms. We will put all this information together to work out how healthcare workers develop antibodies against the virus and if this is affected by the severity of the symptoms is important. We will measure proteins and gene expression to identify how to effectively vaccinate and treat healthcare workers.",2020,2021,University of Nottingham,482303.22,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +C07409,MR/V027867/1,COPE-Birmingham: The contribution of occupational exposures to risk of COVID-19 and approaches to control among healthcare workers,"Healthcare workers have higher risk of getting coronavirus (COVID-19 disease). Contact with infected patients, the type of work and measures such as use of masks affect their risk. However, factors outside the workplace are also important. For example, being older, from minority ethnic groups, some health conditions and home circumstances increase risk. We don't know how these aspects compare with workplace risks, or which work exposures are most risky. We will invite about 5000 staff with different job-roles and departments from three large West Midlands NHS Trusts (University Hospitals Birmingham, Birmingham Women's and Children's and The West Midlands Ambulance Trust) to join our study. These will include workers who had a COVID-19 test because of symptoms. We will also invite some workers with no symptoms. Participants will be asked to complete a questionnaire covering: - type and nature of work - extent and nature of contact with COVID-19 patients (direct, cleaning, transport etc) - ability to comply with recommended infection control procedures - home/family circumstances - travel patterns - personal data and health conditions We will compare workplace exposures and other characteristics amongst those who had positive with those who had negative tests. Our findings will help us to better understand the risk of infection among healthcare workers and to develop guidelines to reduce risk.",2020,2022,University of Birmingham,295847.86,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +C07410,MR/V027794/1,Evidence-Based Supported Digital Intervention for Improving Wellbeing and Health of people living in Care Homes (WHELD) During COVID-19,"The COVID-19 crisis is severely affecting care staff and the 400,000 older people living in care homes. Care home residents include the frailest members of society, many with dementia, mental and physical health symptoms. Care home staff are finding it challenging to provide support in these times and they face an increasingly difficult and distressing work environment. We urgently need to support care staff and provide the best environment possible for care home residents. Our care home training (WHELD) has shown benefits in two large clinical trials; and we have also demonstrated benefits from a digital version, incorporating virtual supervision in a new trial. We will optimise this programme by adapting it for the COVID crisis, to include peer networking and solution sharing. This will add to the person-centred approach, enhanced activities and reduction in sedative medications that the current WHELD programme already achieves. This digital intervention with virtual supervision will be available to 160 care homes within 4 weeks. We will further improve eWHELD based on benefits, feedback and barriers to implementation, make it available to almost 1500 care homes during the programme and ensure that it is ready to roll out to all UK care homes.",2020,2022,University of Exeter,818904.94,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other | Unspecified,Caregivers,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07411,MR/V027778/1,"Quantifying the association between COVID-19, ethnicity and mortality: A cohort study across three UK national databases","Purpose: Early evidence suggests increased severity of COVID-19 disease amongst Black, Asian and Ethnic minority (BAME) groups. There is limited evidence from population-based cohorts at scale across the UK or internationally that quantify within BAME group differences, or examine these in relation to modifiable risk factors. Aim: To describe the prevalence of confirmed COVID-19 cases by ethnic group in a large and representative sample of UK adults, and to quantify the association between ethnicity and mortality stratified by COVID-19 infection and modifiable clinical and social risk factors (blood pressure, HbA1c level, total cholesterol, Body Mass Index, smoking status, co-morbidities, medication use, domicile and household number). Methods: A cohort study of adults registered across three large national primary care databases in England with over 5000 practices representing over 40% of the UK population. Participant sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared by higher level ethnic group (White, Black, Asian and Mixed Other) and their subgroups. For example, the Asian subgroup includes Pakistani, Indian, Bangladeshi or Chinese while the Black subgroup includes African or Carribean as per the 2011 census. Hazard ratios and 95% confidence intervals for all-cause mortality and COVID-19 mortality, adjusted for potentially confounding factors will be calculated using Cox's proportional hazard regression. Implication: Our findings could provide rapid evidence on patterns of COVID-19 and associated mortality across and within ethnic groups in the UK. This has the potential to inform targeted mitigation public health strategies, and could alter clinical thresholds for at-risk patients presenting with the infection.",2020,2022,"University of Oxford, University of Southampton",215753.93,Other,Asian | Black | White | Mixed,Adults (18 and older),Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity,2020 +C07412,MR/V027549/1,UK-REACH: United Kingdom Research Study into Ethnicity And COVID-19 outcomes in Healthcare workers,"Globally many people, including healthcare workers (HCWs), are becoming ill and dying from COVID-19. We have evidence that people from ethnic minorities have a higher chance of going to intensive care and adying from COVID-19.This may also sbe the case for ethnic minorities working in the health system. We want to investigate this using existing data held by national healthcare organisations to understand what the risk of having, and dying from, COVID-19 is for ethnic minority HCWs. We will also follow a group of ethnic minority HCWs over 12 months to see what changes occur in their physical/mental health. In addition we will interview a smaller group of ethnic minority HCWs to understand how risky their jobs are, and how they have changed their professional/social behaviours in response to COVID-19. Using staff data and linking it to healthcare data may be sensitive and so we will explore how to do this in a way that is acceptable. Finally, we want the findings of this research to be useful for HCWs and so we have a stakeholder group of major national organisations to help us do the research, publicise the findings and make recommendations.",2020,2022,University of Leicester,1427135.22,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Health Personnel,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts,2020 +C07413,MR/V020536/1,Ethnicity and COVID-19: investigating the determinants of excess risk in UK Biobank,"What is the problem? People from minority ethnic groups seem to be disproportionally affected by COVID-19, particularly South Asian and Black and African Caribbean communities. What has been done so far? National datasets have shown that minority ethnic groups are up to 4 times more likely to die from COVID-19. However, the reason for this increased risk is not known. What are we going to do? We will use a large dataset, called UK Biobank, which has been linked to national COVID-19 data. Within this dataset, we will use statistical modelling to examine whether the increased risk in minority ethnic groups is explained by differences in underlying health status, lifestyle behaviours such as physical activity, and environmental factors such as air pollution or measures of social inequality. Why is this important? This work will start to unpick why minority ethnic groups may be at increased risk and whether this increased risk is spread equality across the population. For example, is the increased risk explained by a higher burden of other diseases such as heart disease or diabetes or by living in more polluted areas? Do otherwise healthy individuals from minority ethnic groups still have an increased risk? Addressing these question will help inform public health priorities and actions.",2020,2021,University of Leicester,84482.93,Other,Asian | Black | Other,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility,2020 +C07414,MC_PC_20017,AERosolisation And Transmission Of SARS-CoV-2 in Healthcare Settings (AERATOR),"Aerosolisation of SARS-CoV-2 during clinical procedures is a major concern. The safe resumption of essential NHS services is impaired by the need to mitigate the theoretical risk of cross infection from procedural aerosolisation. This includes extensive preoperative planning, use of personal protective equipment (PPE) throughout, and delays in patient/staff movement before, during, and after the procedure. There is currently little to no evidence on aerosolisation risk for many procedures, hampering national guidance and greatly reducing NHS capacity. The AERATOR study will address a critical gap in evidence by quantifying the concentration, size and temporal and spatial dynamics of aerosols produced during routine medical & surgical procedures in different environments. This will focus on five clinical specialties particularly impacted by procedural aerosolisation: dental, orthopaedic, respiratory, critical care and ophthalmology. This work comprises three workstreams: Workstream 1: Within the Bristol Aerosol Research Centre (BARC) we will rapidly (within 4 weeks) validate instruments to study aerosolisation in clinical settings. Workstream 2: Instruments will be moved into clinical settings and, using multiple instruments and sampling techniques, will measure aerosolisation dynamics and size across time and space. Workstream 3: By using novel equipment, only available within Bristol, to levitate virus within a CL3 laboratory, we will investigate the survival of SARS-CoV-2 in aerosol particles and determine its infectivity. The information gathered in this study will allow us to inform hospital trusts, policy makers and Public Health England regarding the safe and maximally efficient NHS working across multiple specialties.",2020,2021,North Bristol NHS Trust,287801.36,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07415,MC_PC_20016,HICC: Humoral Immune Correlates for COVID19: Defining protective responses and critical readouts for Clinical Trials of Vaccines and Therapeutics,"A critical gap in knowledge is our understanding of immune correlates of protection from COVID-19, and the fine specificity of protective immune responses to SARS-CoV-2. Thisgap is a huge impediment to an entire spectrum of major health care issues, ranging from return to work policies for NHS staff and recovered patients to guiding therapeutic interventions, vaccine development and clinical trials. The WHO cautions that simple antibody tests do not correlate with immunity. In fact robust responses correlate with disease severity, while lower titre responses are associated with accelerated viral clearance (Tan et al, medRxiv https://doi.org/10.1101/2020.03.24.20042382). It isessential to have more specific, qualitative humoral assays and Immunoglobulin (Ig) teststhat clearly identify protective immunity, and distinguish from deleterious responses to be avoided by vaccination.We will characterise the; fine-specificity of anti-SARS-CoV-2 antigen (i.e. S, RBD, N) specific Ig, cross-reactivity (i.e. of anti-S2) to other circulating human Coronaviruses (HCoV), correlation of Ig Fc-binding glycosylation patterns with Fc-gamma receptors used, with Immunoglobulin effector functions such as Neutralisation, Antibody dependent enhancement (ADE) and Antibody dependent cellular cytotoxicity (ADCC). The powerful combination of diagnostic, high throughput MS and comprehensive functional analysis will be applied to 3 clinical cohorts; 1) severe COVID-19 (progressors), 2) survivors(moderate) and 3) mild or asymptomatic cases. This study has already been initiated with the aim of; quickly providing essential data for critical clinical decisions for management of NHS staff, while providing standardised testsfor intervention therapies, vaccine development and immune benchmarks for clinical trials.",2020,2022,University of Cambridge,1055546.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Disease pathogenesis | Supportive care, processes of care and management",2020 +C07416,MC_PC_20030,COVID-19 Longitudinal Health and Wellbeing - National Core Study (LWH-NCS),"The Longitudinal Health and Wellbeing National Core Study will improve understanding of C-19 infection risk factors, examine the physical and mental health consequences of asymptomatic to hospitalised cases, and assess the impact of population scale mitigation policy. We will unite distinct, but complementary, longitudinal studies already engaged in C-19 research, including UK representative population and hospitalised cohorts, household panel surveys, and national primary care registries. These will be enriched with health and administrative data linkage. Linkage, self-reporting and repeat serological assessment will allow greater precision in case assignment. This collective resource will be mined by a consortium of experienced analysts linked to these resources to provide rapid answers to existing and emerging priority research questions. For the first 6 months, these include short- and medium-term physical and mental health impacts of those who have had C-19 infection, risks of re-infection and role of risk factors, health effects of interruption to health care services, and the interplay between socioeconomic and health effects of viral suppression policies. Our outputs will include briefing notes as well as scientific reports in order to optimise policy influence.",2020,2021,University College London,13116460,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07417,MC_PC_20029,COVID-19: Data and Connectivity - National Core Study (D&C-NCS),"The Data and Connectivity study sits across the other National Core Studies and aims to build a national health data research capability to support COVID-19 research questions, ensuring datasets are discoverable and accessible and linkages are established to answer the priority research questions from the other five National Core Studies. Making data available for wider research use will increase the scope of benefits beyond the specific studies above, leading to unexpected benefits and boosting UK research capacity more generally, increasing return on investment for the NCS programme. Data integration and harmonisation of methods and standards will enable rapid research and development of new interventions and technologies across the spectrum of COVID-19, and knowledge and technology transfer to other clinical and public health areas. Over the next 6 months the Data and Connectivity study will: 1. Map the initial high priority COVID 19 datasets required by the National Core Studies. 2. Deliver the necessary data infrastructure and services (quality and timely data, ability to link the data and provide access to data for multiple researchers) in 5 Trusted Research Environments across the UK to allow the initial high priority research questions to be answered efficiently in a transparent and trustworthy way. 3. Deliver a single ""shop window"" for the COVID-19 National Core Studies to ensure the priority datasets for COVID 19 research are findable, accessible, interoperable and reusable (FAIR) by enhancing the UK Health Data Research Innovation Gateway Collation and linkage between datasets is critical to bringing the core studies together, ensuring that each of them can deliver against their policy priorities e.g. hospital data may not currently be linked with GP data and wider community data (e.g. socioeconomic data or data on housing and the built environment). Access, cleaning, linkage and use of these datasets together is needed to fully understand links between these factors and outcomes.Delivery of the COVID-19 Data and Connectivity Study will involve close interaction with data custodians, the public and patients, and providers of UK-wide national Trusted Research Environments (TREs) to ensure the required data is stored safely and securely, made readily available to approved researchers and is associated with compute, analytical and data services that make it easier to address priority research questions in a transparent and trustworthy way.",2020,2021,Health Data Research UK,10945900,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2020 +C07418,EP/V053507/1,"RAMP Continuity Network: Scientific Meetings, Rapid Review Group, and Policy Support for COVID-19","Since its inception in late March, RAMP (Rapid Assistance in Modelling the Pandemic) has initiated many new projects and activities and involved in COVID-19 research several hundred scientists whose skill sets complement those of the traditional epidemic modelling community. The majority of substantive new research projects have sought or will seek individual continuity support from UKRI and can also draw on data support, discussion forums infrastructure, and central admin at Edinburgh funded already by UKRI (PI: Ackland). The current proposal is to sustain and add value to RAMP's new research ecosystem, and enhance its connectivity to other COVID-19 research activities across the UK, by funding continuation of key RAMP activities for a further 18 months in the following areas. (i) Scientific networking, to include discussion meetings, study groups, and workshops involving RAMP, SPI-M and other teams; these events organized primarily via the Isaac Newton Institute. (ii) RAMP's Rapid Review Group, based at Oxford, which scrutinizes outputs and reports (from RAMP, SPI-M, third parties and the open literature) so as to better inform Government and its advice channels. (iii) Policy work staffed by the Royal Society to ensure the scientific outputs of RAMP and others land correctly within Government to maximize their policy value.",2020,2022,University of Cambridge,693686.77,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +C07419,EP/V051679/1,Rapid Decontamination System of PPE and Medical Equipment for Reuse using Flexible Non-thermal Plasma Generator,"This project aims to develop a method and procedure for decontaminating mask/respirators using non-thermal plasma for safely reuse. As a respirator is a basic personal protective equipment (PPE) to protect frontline healthcare workers against COVID-19, the chronic, global shortage of N95/N99 masks is one of the most urgent threats to our collective ability to save lives from the coronavirus. The reuse of masks may need to be considered as a crisis capacity strategy to ensure continued availability, even though most of the masks are considered one-time use. Moreover, a single-use mask is adding to the glut of plastic pollution threatening the health of oceans and marine life, environmentalists warn. In this project, we are developing a rapid and safe dry decontamination method through adapting the state-of-art plasma technologies and printed electronics. The proposing approach will use the viricidal capability of non-thermal plasmas to decontaminate masks without using biocidal chemicals and remaining any chemical residues. The project will ensure the safe reuse of masks with maintaining structural and functional integrity with the biological and material assessments. Specific objectives of the project include (1) preparing and validating coronavirus samples; (2) developing a plasma decontamination system; (3) quantifying concentration and distribution of biological samples before and after plasma treatment; (4) measuring the effect of plasma treatment on mask performance; (5) quantifying viral inactivation efficiency; and (6) collating and interpreting results to assess the efficacy, promise, and potential implementation pathway for the concept. Through opening up re-use of masks, this project will provide a new solution for current PPE shortage for acute global mask shortage and minimise plastic pollution.",2020,2022,University of Southampton,345452.87,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C07420,EP/V051571/1,Improved face-worn PPE designs for use by the public and professionals to reduce audio-visual communication difficulties,"To reduce the transmission of COVID-19, personal protective equipment (PPE) is required. PPE to protect the eyes, nose and mouth comprises face masks and transparent visors. These range from a simple covering made from domestic fabrics for use by the public, to FFP3/N99 rated air filters and wrap-around face visors in care settings. All these PPE styles make spoken and signed communication harder. Everyone, not just the hearing impaired, will struggle to understand in real-world conditions and background sounds. This will result in increased listening effort, stress, communication errors and potentially social withdrawal. Articles published in May 2020 by the PI and his group leader in a professional journal (https://www.entandaudiologynews.com/features/audiology-features/post/the-challenges- of-facemasks-for-people-with-hearing-loss) produced over 100 responses from anxious adults, parents, public and professionals. Both acoustic and visual cues are reduced by face coverings: (i) acoustic : the high frequencies of the sound are attenuated, leading to a ""muffled"" perception (ii) visual : sight of the talker's mouth movements that can be used by all listeners to supplement the muffling of speech and (iii) visual : full-facial expressions that convey emotions, supplement lip-reading and are essential components of (the non-acoustic) British Sign Language (BSL). Employing user surveys, fabrication, and testing, this project will produce validated examples of facemask and visor designs that preserve acoustic and visual cues thereby offering less effortful communication in a variety of usage scenarios. It brings together acousticians, audiologists, material scientists, and users to tackle an urgent problem that affects everyone now, and will also outlast the current pandemic.",2020,2021,The University of Manchester,170612.4,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07421,EP/V051555/1,Uncertainty Quantification for Expensive COVID-19 Simulation Models (UQ4Covid),"Accurate mathematical models of transmission are crucial for targeting successful interventions to combat the spread of SARS-Cov2. In the UK, established models are used to provide real time policy support to Government through the Scientific Pandemic Influenza group - Modelling (SPI-M). Modellers in SPI-M have a proven track record, and models are continually adapted to respond to the evolving pandemic. When using models to inform decision making, it is crucial that all sources of uncertainty are properly accounted for when calibrating and predicting. For 30 years the UK has been a world-leader in developing Uncertainty Quantification (UQ); delivering methods for formal treatments of uncertainty when using models to understand the world, allowing efficient and robust calibration and prediction. Despite this, these techniques are not currently in place for COVID-19 simulation models, leading to slower-than-necessary adaptive model development-UQ allows for fast re-calibration-and an under-representation of uncertainty in predictions delivered to policymakers. This project will adapt and deliver UQ techniques, code and tutorials for models of COVID-19 in the UK, providing SPI-M modellers with tools to facilitate rapid re-calibration of their models when changes are made in response to the evolving pandemic, and to more accurately represent uncertainty in their predictions. We will work closely with MetaWards, a spatial meta-population transmission framework (Danon et al. 2009, 2020) that contributes to SPI-M, to develop and apply these tools as we move into the winter; enabling fast evaluation of interventions responding to localised outbreaks, efficacy of vaccine rollout strategies, duration of immunity and more.",2020,2022,University of Exeter,384076.07,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2020 +C07422,EP/V050761/1,COVID-19: An Algorithmic Model for Critical Medical Resource Rationing in a Public Health Emergency,"The aim of the project is to develop an algorithmic model that calibrates a dynamic index for patient priority by addressing the shortcomings of the current allocation protocols of scarce medical resources. The total number of confirmed Covid-19 deaths in the UK has already passed the 45,000 mark. Such a horrific number of deaths is partly attributable to the shortage of PPE, medical staff, and ICU beds in the early stages of UK pandemic. For a second wave of Covid-19 likely in the winter when the healthcare system is most stretched, scientists have estimated that the UK could see about 120,000 new coronavirus deaths. To achieve the greatest good for the greatest number of patients, it is essential to have in place ethically and clinically sound policies on the allocation of scarce resources. Existing triage guidelines determine patient priority based on several attributes, including the illness severity and the near-term prognosis after discharge. They focus on individual patients but ignore the overall mixture of current patient profiles and the uncertainty in the number of patients who become critical ill over time. Previous research has shown that such frameworks could lead to preventative deaths and inefficient usage of scarce resources. We aim to address these limitations in this project via the development of an algorithmic model that calibrates a dynamic index (priority). Its performance is to be compared against the benchmarks via an empirical study using anonymised data of Covid-19 patients collected by Public Health England.",2020,2021,Durham University,153533.87,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C07423,EP/V050516/1,The Investigation of Particulate Respiratory Matter to Inform Guidance for the Safe Distancing of Performers in a COVID-19 Pandemic (PERFORM-2),"Respiratory particles emitted during human exhalatory events by an individual infected with SARS-CoV-2 are known to span a wide size range, from large macroscopic droplets to small aerosol particles. Although these droplets (>5 micrometres diameter) and aerosols (<5 micrometres) are responsible for direct, indirect and airborne modes of viral transmission, the concentrations and fluxes expired during activities such as speaking, singing, playing musical instruments and exercising, are poorly quantified and, in some cases, remain completely unknown. An absence of data, essential to inform assessments of risk in restarting activities, has led to precautionary measures that severely restrict singing, musical performance and sport, across both the amateur and professional domains. Building on preliminary work with a cohort of professional musicians, we will provide a comprehensive analysis of aerosol and droplet emissions from singers covering a broad range of genres, as well as woodwind and brass instruments. Working in an orthopaedic operating theatre, an environment of ""zero aerosol"" background, we will extend our study to quantify respirable particles exhaled by amateur musicians and individuals undertaking exercise, explore rigorously the distance of large droplet transmission and aerosol flux, focusing on super-emitters, and work with speech and language therapists to understand the risks of aerosol generating procedures used during therapy. In a range of venue types (from a modern auditorium to an historic church), we will measure the dynamics of aerosol dispersion and clearance, informing computational fluid dynamics models of aerosol spread and assessments of exposure risk.",2020,2021,University of Bristol,579348,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07424,EP/V050168/1,INSIGHT - medIcal oxygen supply chaiN deSIGn and planning for COVID-19 HospiTals,"With the evolution of the ongoing SARS-CoV-2 pandemic becoming increasingly uncertain and oxygen-therapy being the current dominant treatment of patients, securing resilient and robust operation of medical oxygen supply chains becomes increasingly urgent. INSIGHT will develop a whole-systems analysis on the integrated design and operation of medical oxygen supply chains in the UK for current, future waves of SARS-CoV-2 as well as for other pandemics and cases that require emergency planning. A key uniqueness of INSIGHT is the spatially-explicit and uncertainty-aware modelling of supply chains which will provide a roadmap to region-specific strategies for coping with different realisations of future COVID-19 waves. Our optimisation-based framework for enhanced decision making for emergency planning will be open-source, publicly available and due to the design of INSIGHT could be easily generalised to inform European and low and middle income countries (LMICs) strategies. To this end, we propose to combine methodologies from supply chain optimisation, multi-scale modelling and stochastic optimisation. Through our long-standing collaboration with Linde.plc we have been developing models related to the air separation industry. Finally, we have secured the active participation of BOC, one of the two NHS bulk medical oxygen providers, so as to maximise the impact and applicability of INSIGHT's outcomes.",2020,2022,University College London,468527.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2020 +C07425,EP/V049771/1,DisCoVer: Aptamer biosensors for the detection of SARS-CoV-2 on surfaces,"The high survivability of SARS-CoV-2 on surfaces, such as metal, plastic, glass and some fabrics, means that fomite transmission is likely to play a key role in the spread of nosocomial COVID-19 infections. With effective vaccines or counteractive drugs against the virus yet to be fully realised, effective monitoring of surfaces potentially contaminated with SARS-CoV-2 is vital to managing infection rates and protecting healthcare workers. However, such environmental monitoring efforts are limited by the length of current viral testing processes (i.e. through swabbing, genomic extraction and RT-PCR), which prevents the identification of viral contamination in real-time. Biosensors, a group of molecules able to produce measurable signals in response to biological interactions, may overcome these challenges by allowing the rapid, specific and sensitive detection of SARS-CoV-2 in situ, without the need for extensive processing or specialised equipment. This work will therefore involve the development of an optical biosensor towards SARS-CoV-2 based on aptamer recognition. Through delivery to surfaces as part of an aerosolised spray reagent, this sensor will allow the 'stand-off' visualisation of viral deposits through the production of discrete areas of fluorescence thereby allowing healthcare workers to quickly triage objects in need of decontamination. Biosensor construction will be based on a 'molecular beacon' design, in which an initially quenched dual-labelled probe is restored to a fluorescent state upon SARS-CoV-2 binding. Fluorescence emission signals will be provided by bright and highly stable conjugated polymer nanoparticles, whilst molecular dynamics simulation and modelling studies will be used to ensure high biosensor specificity/sensitivity.",2020,2022,King's College London,510271.79,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C07426,EP/V048597/1,Learning from COVID-19: An AI-enabled evidence-driven framework for claim veracity assessment during pandemics,"The term 'infodemic' coined by the WHO refers to misinformation during pandemics that can create panic, fragment social response, affect rates of transmission; encourage trade in untested treatments that put people's lives in danger. The WHO and government agencies have to divert significant resources to combat infodemics. Their scale makes it essential to employ computational techniques for claim veracity assessment. However, existing approaches largely rely on supervised learning. Present accuracy levels fall short of that required for practical adoption as training data is small and performance tends to degrade significantly on claims/topics unseen during training: current practices are unsuitable for addressing the scale and complexity of the COVID-19 infodemic. This project will research novel supervised/unsupervised methods for veracity assessment of claims unverified at the time of posting, by integrating information from multiple sources and building a knowledge network that enables cross verification. Key originating sources/agents will be identified through patterns of misinformation propagation and results will be presented via a novel visualisation interface for easy interpretation by users. This high-level aim gives rise to the following objectives: RO1. Collect COVID-19 related data from social media platforms and authoritative resources. RO2. Develop automated methods to extract key information on COVID-19 from scientific publications and other relevant sources. RO3. Develop novel unsupervised/supervised approaches for veracity assessment by incorporating evidence from external sources. RO4. Analyse dynamic spreading-patterns of rumour in social media; identify the key sources/agents and develop effective containment strategies. RO5. Validate the methods via a set of new visualisation interfaces.",2020,2022,University of Warwick,577394.23,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C07427,EP/V045563/1,A BioEngineering approach for the SAFE design and fitting of Respiratory Protective Equipment (BE-SAFE RPE),"Respiratory protective equipment (RPE) is widely used to limit the transmission of viruses and bacteria, representing a critical means of controlling Covid-19. In particular, respirator masks of the FFP3/N95 types, originally designed to protect against airborne dust particles, have been widely used to protect healthcare workers (Fig 1). It is essential that these masks fit tightly against the face to make an airtight seal, checked by fit testing. However, these masks are typically designed for a white male workforce, providing a limited range of size and geometry. This can lead to overtightening to compensate for a poor fit, which is associated with soft tissue injuries, as well as an increased risk of infection. This multidisciplinary project will investigate the fit and biomechanics of RPE devices, to ensure provision of a safe interface with users. Computational modelling and MRI will be used to explore how the soft tissues of the face deform in contact with a mask. These models will be informed through experimental monitoring of mechanical and thermal loads during RPE application and the associated changes in local skin physiology. In addition, the project will utilise existing databases of face shapes to investigate the fit of masks on a more representative range of users. This will lead to the development of design templates for new masks (working with UK manufacturers), standard test methods (STMs) to evaluate the risk of facial injury (working with testing and standards organisations), and intelligent fitting software to ensure that users select the correct mask.",2020,2022,University of Southampton,470393.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07428,EP/V044036/1,"CoRLEIT, Covid Regional Lung EIT","A key challenge for the COVID-19 pandemic is the requirement to monitor for deterioration and provide timely escalation interventions to an unprecedented number of patients at risk of respiratory failure. Existing monitoring poorly predicts sudden deterioration in COVID-19 pneumonia. Regional information, currently from CT scans, has been informative (Scudellari, 2020) [1], but does not provide dynamic information. There is an urgent need for a low cost, bedside, non-invasive imaging system, to continuously monitor dynamic changes in regional lung ventilation [2][3][4][5]. Electrical Impedance Tomography (EIT) can provide this and has proved useful in managing acute respiratory syndrome in infants and adults (Bachmann et al 2018) [2]. We have already developed a low cost wearable EIT system for neonates (CRADL; http://cradlproject.org/) and obtained clinical results from 200 subjects, each for up to 72 hours of continuous monitoring of temporal lung volume changes. This technology can be repurposed for COVID-19 patients (Appendix) with the aim of providing novel insights into COVID-19 pathophysiology, and with the potential to provide a solution for respiratory failure monitoring at scale. Using EIT in HDU-pre-ICU patients, evaluating and stratifying treatment response (to prone positioning, CPAP, other breathing support) and then following through into ICU with ventilation interventions if they deteriorate, will add invaluable information about how COVID-19 effects the respiratory system. This will establish the merits of EIT monitoring for COVID-19 respiratory failure, in particular enhance and expedite clinical research into optimal COVID-19 breathing support treatment strategy and facilitate development of EIT guided personalised treatment plans.",2020,2022,Middlesex University London,706742.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C07429,EP/V043811/1,Antiviral Personal Protective Equipment,"Coronaviruses are transmitted from an infectious individual through large respiratory droplets generated by coughing, sneezing or speaking. These infectious droplets are then transmitted to the mucosal surfaces of a recipient through inhalation of the aerosol or by contact with contaminated fomites such as surfaces or other objects. In healthcare settings, personal protective equipment (PPE) plays a crucial role in interrupting the transmission of highly communicable diseases such as COVID19 from patients to healthcare workers (HCWs). However, research has shown that PPE can also act as a fomite during the donning and doffing process as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive on these surfaces for up to three days. This creates a need for more effective PPE materials that can provide antiviral protection. In this proposal we aim to develop a dual action antiviral/antifouling coating to lower the risk of transmission of the SARS-CoV-2 to HCWs from COVID19 patients. This project will deliver antiviral/antifouling coatings that can be readily applied to PPE surfaces such as faceshields that are likely to encounter a high level of viral load and would be of great benefit to the health of clinical staff. Furthermore, this project has embedded into its planning a rapid pathway for optimisation, translation, and upscaling of manufacture to deliver a low-cost technology within a short timescale.",2020,2022,University of Liverpool,654215.03,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07430,EP/V043714/1,Establishing lung ultrasound as a key tool in the stratification and monitoring of COVID-19 patients,"Lung ultrasound (LUS) is a powerful tool for the diagnosis of different pathologies of the lung. As the main cause of death in COVID-19 patients is from pneumonia, simple, low cost and effective techniques for monitoring the lungs of patients is critical. This proposal seeks to develop the necessary tools to ensure LUS can achieve this in the short and long term. The first goal of this proposal is to rectify the fact that there are currently no computer simulations of LUS for researchers to run simulations with. Implementing this model in free to use software will allow for the rapid study and optimisation of LUS by the research community. The second goal of this proposal is to implement a recently developed ultrasound beamformer for use with the range of transducers used in LUS. This novel beamforming technique has been demonstrated to improve the contrast to noise ratio and spatial resolution of ultrasound images, which enhance the detection of lung pathologies associated with COVID-19 patients. Once validated on lung mimicking phantoms and a healthy volunteer, this technique will be published in an open access journal for implementation on any other ultrasound system. The final goal is to establish a secure repository of clinical LUS images, which can be used to train deep learning networks in order to 'de-skill' the use of LUS. Furthermore, we will implement a weakly supervised deep learning network to test these datasets and those acquired from test phantoms.",2020,2022,University of Leeds,281622.18,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C07431,EP/V043277/1,Rapid Multi-antigen COVID-19 Point-of-Care Antibody Test from a Pin-Prick Blood Sample,"The aim is to develop a point-of-care (POC) device to determine the immune status of an individual to SARS-CoV-2 from a pin prick blood sample in under 10 minutes. The POC device have at its core a disposable, single sample cartridge containing an array of up to eight film bulk acoustic resonator (FBAR). FBAR sensors have the potential to significantly advance the state-of-the-art in COVID-19 testing as they offer a small form factor (each sensor has an active area of 100x300 micron on a 0.7 mm silicon die), high sensitivity, high dynamic range, economical manufacture at scale, and can measure binding of proteins from within whole blood samples without the need for lysis, centrifugation or other pre-processing. The FBAR sensor array, encased in a single use cartridge together with integrated microfluidics, will simultaneously quantitate antibodies against multiple SARS-CoV-2 protein domains (S1, S2, receptor binding domain, N protein), as well as epitopes known to be critical for viral neutralisation. This multiplexed quantitation, together with the high sensitivity of the sensors and automated interpretation algorithms in a small form factor reader, will allow us to achieve the high specificity and sensitivity required by MHRA's target product profile for serology with tiny blood volumes at unprecedented speed. The product would allow rapid quantitation of COVID-19 immune status as the COVID-19 outbreak persists. It would partner rapid RT-PCR based viral detection (e.g. Cepheid) as key tests directing infection control in healthcare and other settings where high transmission risk exists, democratising access to testing.",2020,2022,University of Cambridge,752553.9,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07432,EP/V041789/1,COVID-19: Patient-specific lung models to guide interventions prior to clinical application,"This project will deliver computational models of the lung, to support the development of patient-specific treatment strategies for the COVID-19 pandemic. The models will i) automate analysis of the damaged lung, providing additional quantitative data to support more reliable and rapid conclusions about the presentation of the virus, ii) provide predictions of how the lung will perform in response to different management strategies (supplemental oxygen, mechanical ventilation, fluid balance) and potential future treatment strategies outlined in the RECOVERY/REMAP-CAP trial (e.g. steroids, anti-inflammatories, antibiotics and plasma from recovered patients); innovatively factoring specific parameters such as weight, height, age, general fitness and ethnicity - which unquestionably have acute relevance for recovery. COVID-19 is heterogenous - affecting everyone differently. Therefore, rapid and appropriate medical responses to individual cases are critical. Presently patients can remain on ineffective treatment pathways for 4-6 hours before alternative treatment strategies are employed. This project reduces waiting times, enabling prioritisation based on quantitative tools. The models deliver heightened understanding of individual lung mechanics, enabling clinicians to quickly make better informed treatment decisions to optimise COVID-19 survival rates. The model will use patient CT data, patient-specific calibration factors (age, sex, size) and risk factors (comorbidities, clinical frailty score, exercise tolerance, APACHE-II, ethnicity), state-of-the-art image analysis and computer simulation, in collaboration with 3DLifePrints to build human lung models. Patient data will be accessed via ICNARC and the SAIL databank. The model will mimic lung structure and mechanical function, accounting for the effect of tissue damage and providing dynamic feedback of lung health.",2020,2022,Swansea University,344960.77,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C07433,EP/V041541/1,"Light-activated, disposable antiviral and antimicrobial plastic films for PPE and other applications","Idea: Dyes and semiconductor photocatalysts are able to generate a myriad of reactive oxygen species which destroy viruses and bacteria. However, never before has this technology been harnessed to make inexpensive, disposable anti-virial and anti-microbial plastic films before and this is the primary aim of this research proposal. At present in hospitals and care homes thin plastic disposable films are common in PPE (e.g. gowns and aprons) and curtains and coverings for bedside cupboards and tables; but these films do not have any antiviral or antimicrobial activity, despite the fact that this feature is desperately needed as many viruses and bacteria are able to survive on plastic surfaces for several days (for COVID19: it is 3 days!); this project addresses this need. The key work packages involve: (i) Extrusion of thin, flexible antiviral/antibacterial plastic films containing either a visible light absorbing photocatalyst or dye; with different dyes and photocatalysts to be tested to produce an optimised product. (ii) Testing of plastic films for antiviral activity and feedback to film production - so that an optimised product can be generated (iii) Testing of plastic films for antiviral activity and feedback to film production - so that an optimised product can be generated (iv) Engagement with commercial providers of healthcare PPE and related products, such as Clonallon Ltd. a collaborator, in order to identify the best route to market. Potential: As the materials to be used are inexpensive, the method of production of the thin plastic films easily scaled, the likely impact is immeasurable.",2020,2022,Queen's University of Belfast,396026.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07532,GA92072,Digging Deeper - Exploring the Effects of Coronavirus (COVID-19) Pandemic on Social Connectedness and Mental Health,Unsure,2020,2021,Australian National University,139325.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07533,GA127021,Cellular and molecular correlates to SARS CoV2 immunity in convalescent patients,Studying the natural infection and the level of immunity across these patient groups with varying disease characteristics will support: - understanding the immunological correlates of protection against SARS-CoV-2 infection - understanding how genetic variation between SARS-CoV-2 isolates (as the virus mutates) affects the immune response of different patient groups.,2020,2022,UNSW Sydney,716100.48,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2020 +C07534,GA85470,Novel inhibitors of SARS coronaviruses targeting ACE2,,2020,2021,Burnet Institute,225389.98,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07535,GA143554,Understanding novel viral host interactions that modulate innate immunity,"Lethal viruses such as coronaviruses (MERS, SARS-CoV-1, SARS-CoV-2), Dengue, Zika, Hendra, and Nipah have developed effective mechanisms of replication by dampening the host immune system. Here we will examine how viruses carry out these immune evasion functions, and test antiviral drugs that can prevent these effects in a highly specific manner. If this idea can be proved, it will provide great promise for the development of new antivirals whilst minimising the toxic effects to the cell.",2021,2024,Charles Sturt University,573184.5,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +C07536,GA129719,Defining SARS-CoV-2 immune maintenance in the Australian population,"Control of viruses in humans is dependent on B cells that produce antibodies to recognise and neutralise virus particles, and T cells that recognise and remove virally infected cells. Currently, we do not know how long these immune cells live for in individuals who have recovered from COVID-19. This must be determined in order to assess the risk of reinfection and identify which part of the population may benefit from vaccine boosters if a COVID-19 vaccine becomes available.",2020,2022,QIMR Berghofer Medical Research Institute,709201.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07537,GA85468,Ivermectin as an anti-viral against SARS-CoV-2,"We have shown that the drug Ivermectin, which is already used in humans to treat a number of parasite infections, is also very effective at preventing the virus that causes COVID-19 from replicating. We have shown this in virus infecting cells in a laboratory and now we will confirm whether it is able to be used in people suffering from COVID-19. As ivermectin is already safe for use, if it is effective against the virus at these safe concentrations it can be rapidly moved into human trials.",2020,2021,Monash University,237676.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Phase 0 clinical trial,2020 +C07538,GA133345,"A safe, effective, and rapidly tuneable SARS-CoV-2 vaccine","In response to the COVID-19 pandemic greater than200 vaccine candidates are in active development and greater than20 in clinical trials. While we hope that these 'first generation' vaccines will be safe and effective, there are sure to be challenges in deploying these vaccines to all parts of the globe, including Australia, in a timely manner. Accordingly, we have developed two vaccine candidates with significant novelty, tempered by realistic deployment imperatives, to be deployed in this global emergency.",2020,2022,University of Melbourne,2129646.42,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C07539,GA85471,Targeting the deubiquitinase activity of Coronaviruses: the VirDUB programme,"SARS-CoV-2 shares mechanisms to efficiently reproduce and infect human cells with previous coronaviruses. We propose to directly drug a viral enzyme, the Papain-like protease PLpro, required for this process. During Stage 1, the VirDUB progam will deploy an accelerated approach to identify potent drugs disabling PLpro. During Stage 2, candidate antivirals will progress through already established clinical trials to offer benefit to patients and health professional for prophylaxis and treatment.",2020,2021,Walter and Eliza Hall Institute of Medical Research,800902.72,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C07540,GA143624,Better statistical methods to discover host genetic factors in symptom response to SARS-CoV-2 infection,"The COVID-19 pandemic has infected greater than5 million people worldwide. While the majority of infected individuals recover within a few weeks of infection, others develop severe forms, that in some cases prove fatal. To date, the causes of differences in symptom response are unknown. In this proposal, we seek to discover genetic factors that can contribute to explaining these differences. Our findings have the potential to inform the design and analysis of clinical trials for vaccines and treatments.",2021,2023,University of Queensland,217602.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,Prognostic factors for disease severity,2021 +C07541,GA85467,Monoclonal antibody therapy of COVID-19,"The 2019/20 coronavirus (COVID-19) outbreak originating in the Wuhan province of China represents a major health emergency. In the earlier 2003 outbreak protective antibodies against the highly related SARS coronavirus have been described. Intriguingly, recent data indicate that these antibodies may not only be applicable to SARS, but also to COVID-19. Here we outline a strategy to develop these antibodies for COVID-19 therapy.",2020,2021,Garvan Institute of Medical Research,410149.86,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07542,GA143517,Manipulating antibody production to maximise memory in vaccine responses,"Our immune system provides protection from germs. The secretion of germ-specific proteins (antibodies) is an integral component of this defence and the basis of virtually all vaccines. Pandemics of Influenza and SARS-CoV-2 and failure to develop vaccines against HIV and Malaria remind us that our strategies need urgent improvement. Increasing our understanding of how our body defends us by specifically targeting foreign structures will reveal avenues for successful, rational vaccine development.",2021,2024,Monash University,813318,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C07543,GA143552,"Modulating COVID-19 disease by targeting virus and virus-induced responses through pharmaceutical and mechanical ventilation strategies: SARS-CoV-2 S-protein, ACE2 and TMPRSS2","COVID-19 is a current global pandemic that is likely to be an on-going threat. We need a multipronged strategy to combat COVID-19, including therapeutic anti-virals and clinical practice management strategy. We will address both these points to define the mechanisms triggering disease, test existing drugs targeting androgens and modify the way doctors use ventilators to treat COVID-19 disease in the intensive care unit. Outcomes will have impact beyond COVID-19 for managing viral lung disease.",2021,2023,Flinders University,471642,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Pre-clinical studies",2021 +C07544,GA85469,Targeting SARS-CoV-2 using Stealth nanoparticles loaded with gene silencing siRNAs,"We have developed technology that turns off respiratory virus genes, resulting in a 99.9 percent reduction in virus growth in animal models. We have already used it against Hendravirus, RSV, and hMPV. These stealth nanoparticles, made from FDA approved materials, are able to deliver to the infected lung cells via the blood stream, bypassing the inflamed airway that blocks other medicines from working. Here we will explore this for COVD19 virus.",2020,2021,Griffith University,219208.86,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07545,GA85475,Biologics for the prophylaxis and treatment of COVID-19,"Agents for treatments and prevention of COVID-19 infection are urgently needed. Antibodies are widely used to treat several infectious diseases, as well as autoimmune diseases and cancer. Using novel antibody discovery platforms and high-throughput screening approaches, our team of academic and industry partners is uniquely positioned to accelerate the discovery of an effective and safe antibody-based therapy to combat the new pandemic coronavirus.",2020,2021,Walter and Eliza Hall Institute of Medical Research,1511057.58,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C07546,GA137275,Rethinking Medico-Legal Borders: From international to internal histories,"The response to coronavirus has starkly revealed the significance of internal movement and its regulation. Yet the focus of scholarship on medico-legal border control remains almost exclusively on international movement. This project addresses that major gap by researching the regulation of internal movement in past and present pandemic times, with a focus on plague, influenza, SARS and coronavirus in Australia, and in comparison with Hong Kong. It will interrogate the ambiguous internal/international borders of ships in quarantine in the past and in the coronavirus present. Bringing law and history together, this project will clarify how internal movement has been, and can best be, lawfully restricted.",2020,2023,UNSW Sydney,180983.79,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C07547,GA82795,COVID-19 Response - Disability Individual Advocacy Sector,The program enables the provider to coordinate and support the disability individual advocacy sectors response to the emerging needs of people with disability during the COVID-19 pandemic,2020,2020,Disability Advocacy Network Australia (DANA) Limited,112200,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C07548,GA85492,IMPACT-ICO: Trials of Immuno-Modulatory Particles and Colchicine To Improve COVID-19 Outcomes,"The current coronavirus pandemic is highly contagious and carries a significant risk of death. We propose to test a commonly used inflammatory tablet Colchicine and a novel, biodegradable particle which reduces inflamed cells in the hope that this can improve outcomes. The trial will include 240 people needing oxygen treatment and hospital care for the infection. An expert committee together with consumer representatives will oversee the research.",2020,2021,University of Sydney,676486.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C07549,GA142249,Nowcasting outbreaks leveraging genomic and epidemiological data,"This project aims to inform outbreak response planning by developing new models of infectious disease outbreaks. The project expects to generate new knowledge on the processes driving ongoing outbreaks including those of the novel coronavirus (COVID-19) and African swine fever by integrating the latest advances in Bayesian outbreak inference alongside unique simulation approaches. Expected outcomes should include a shift in how models are developed and used to inform the response to outbreaks as they unfold. This should enable more rapid outbreak containment in Australia and overseas, leading to reduced impacts on public and animal health, and associated industries.",2021,2023,The University of Melbourne,192666.75,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Epidemiological studies,Disease transmission dynamics,2021 +C07550,GA85472,Inhaled oligonucleotides to generate a decoy receptor for the SARS Coronarvirus-2,"The SARS-Coronavirus-2 gains access to the human body by binding to ACE2 on the surface of certain cells. We have found a practical way to change ACE2 so that it is no longer on the surface of cells, so can't be used as a conduit for virus entry. Moreover, by still being able to bind to the virus, this soluble ACE2 can act as a decoy receptor to prevent virus accessing other cells. This technology has been approved for use in humans, and represents a novel strategy for COVID-19.",2020,2021,Monash University,204969.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +C07551,GA85473,Convalescent Plasma for COVID-19,"This study will evaluate whether administration of plasma containing antibodies against COVID-19, collected from people who have recovered from the infection, is safe and improves outcomes for patients admitted to hospital or intensive care with COVID-19. In partnership with Australian Red Cross Lifeblood, we will establish the process to collect, test and administer the convalescent plasma. We will then test whether it is safe and effective in two large, multicentre, national clinical trials.",2020,2021,Monash University,256408.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,Clinical trials for disease management,2020 +C07552,GA85499,Delivery of remote workshops to government officials and civil society on countering online disinformation and hate speech campaigns related to COVID-19 and a virtual regional dialogue,"IFES will develop and deliver learning programs that build government and civil society capacity in the region to counter hate speech and disinformation around COVID-19. Project deliverables include a course curriculum on Countering Disinformation and Hate Speech in Emerging Crises; immediate implementation of online training programs and ongoing advisory support; and gathering an evidence base and convening a virtual regional meeting of human rights and fact-checking organizations on the dangers of using new misinformation legal frameworks and COVID 19 emergency powers to limit freedom of speech online (Cyber Strategy Obj. 5.0). Proposed Project Outcomes: 1. Incresed capacity amongst civil society in the ASEAN region to engage with state agencies involved in managing disinformation and foreign interference 2. Strengthened state agencies' approaches on countering COVID19 disinformation and foreign interference/influence in the ASEAN region 3. Increased dialogue between rights organisations, fact checking groups and governement officials that culminates in rights-informed lessons learned for the region",2020,2021,International Foundation for Electoral Systems,276000,Human Populations | Other,Asian,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Americas,Western Pacific,,,,United States of America,Australia,"Policies for public health, disease control & community resilience",Communication,2020 +C07553,GA143495,Determining the impacts of COVID-19 restrictions on people who use drugs,"COVID-19 has resulted in unparalleled government interventions to close borders and restrict social interactions which have major implications for illicit drug supply, procurement and use practices, as well as responses. People who use drugs will be profoundly impacted by COVID-19 and so our study will leverage existing data collections to compare drug use practices and consequences before, during and after the COVID-19 interventions to determine COVID-19 impacts on people who use drugs.",2021,2022,Burnet Institute,354113.31,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C07554,GA85767,Conceptualising and Detecting COVID-19 Mis/Disinformation Dissemination Project,"Support to RAND's research project that will examine COVID-19 related disinformation/misinformation in two geographic regions, South East Asia and the Pacific.",2020,2021,RAND Australia Pty Ltd,75000,Human Populations,Asian | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Policies for public health, disease control & community resilience",Communication,2020 +C07555,GA84650,Regional Collaborations Programme COVID-19,"The grant is to support Australian researchers to work collaboratively with regional economies to address shared regional challenges resulting from the COVID-19 pandemic. It contributes to the achievement of the Regional Collaborations Programme (RCP), part of the Australian Government’s Global Innovation Strategy, under the National Innovation and Science Agenda.",2020,2022,Australian Academic of Science,364138.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Australia,Australia,"Secondary impacts of disease, response & control measures",,2020 +C07556,GA85491,Repurposing existing medications to reduce severe acute respiratory distress in patients with COVID-19: the CLARITY trial,"The CLARITY trial will test whether a group of common blood pressure medications reduce the duration and severity of lung failure due to COVID-19. These medications have been in clinical use for over 30 years. They protect against lung injury in animal studies, including injury from viruses like the COVID-19 virus although the effect in humans is not known. Existing medications that lessen the severity of COVID-19 lung disease could provide some relief for patients and hospitals.",2020,2021,UNSW Sydney,970545.03,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C07557,GA85494,"Tocilizumab for tReatment Of COVID-19 in intensive cARe patients (""TROCAR"")","Severe illness from COVID-19 is associated with a high risk of death. Currently, no proven treatment exists. We will conduct a clinical trial to determine if tocilizumab, a drug used to reduce the adverse effects of inflammation, will improve clinical outcomes in critically ill patients with COVID-19. We will enrol 194 patients from intensive care units in Brisbane, and will determine if a single dose of tocilizumab reduces the duration of ventilatory support, and reduces the risk of death.",2020,2021,QIMR Berghofer Medical Research Institute,192583.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C07558,GA137293,Alcohol consumption practices in crisis,"This project aims to investigate how meanings and practices of alcohol consumption in Australia are impacted by the global novel coronavirus pandemic.The project expects to generate new knowledge in the area of the sociology of alcohol consumption, gender and social media by using assemblage theory and novel scroll-back qualitative interview methods. Expected outcomes of this project include enhanced capacity in researching alcohol consumption practices in times of crisis, theoretical and methodological innovation and practical recommendations for responding to alcohol consumption in and beyond future crises. This should enhance policy and reduce the economic and social costs associated with alcohol use.",2020,2023,Monash University,169862.24,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07559,GA85497,Precision antibiotic strategies to reduce invasive mechanical ventilation and mortality in COVID-19,"We will investigate whether tracheal microbiology predicts duration of mechanical ventilation and death in COVID-19 patients, and determine whether antibiotic therapies can provide benefit through their impact on airway microbes.",2020,2021,South Australian Health and Medical Research Institute,406285.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +C07560,GA85495,USE OF THERAPEUTIC DRUG MONITORING (TDM) TO OPTIMISE ORAL/ENTERAL HYDROXYCHLOROQUINE DOSING IN CRITICALLY ILL PATIENTS WITH COVID-19,"The Royal Brisbane and Women's Hospital Intensive Care Unit Clinical Consultant Medical Staff, in agreement with the Infectious Diseases Department and the Pharmacy Department, have decided that all Covid-19 patients admitted to the ICU should receive hydroxychloroquine as standard of care. This study is to determine whether therapeutic drug monitoring of hydroxychloroquine dosing in Covid-19 patients results in clinically significant alterations in the drug dosing regimen.",2020,2021,Queensland University of Technology,117313.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C07561,GA129718,Identifying the mental health effects and support needs of people bereaved during and following COVID-19: A Mixed Methods Project,"The potential for significant mental health distress following bereavement has been recognised by the World Health Organisation. Bereavement is linked with mental health conditions such as major depression, anxiety and suicidal ideation. Many of the risk factors for poor mental health have been amplified by the COVID-19 pandemic restrictions on gatherings and physical contact. This project will quantify the mental health outcomes and support needs of bereaved individuals impacted by COVID-19.",2020,2022,University of Technology Sydney,531612.5,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07562,GA91805,"The Peter Doherty Institute for Infection and Immunity will lead COVID-19 related activities with select Chinese universities (including Fudan, Hong Kong and Tsinghua universities).","The ad hoc grant contributes to our priority of contributing to the Australian COVID-19 response, consistent with the NFACR's mandate and purpose.",2020,2021,"The University of Melbourne, represented by The Peter Doherty Institute for Infection and Immunity",462000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,,,2020 +C07563,GA85493,ProTreat: an adaptive and rapid implementation trial of novel therapies to prevent and treat COVID19 infection in high risk cancer patients,"Cancer patients are likely to have more severe COVID and need hospital, ICU or die than the general population. Risk of drug reactions will stop them entering other trials.This trial has many points where a patient could join: preventing COVID with antivirus nose spray; higher dose after COVID exposure; treatment of moderate COVID; treatment for impending severe COVID. Each will be compared to inactive treatment. Results will be continually checked to see if the study should stop or be adjusted.",2020,2021,University of Melbourne,1497253.08,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C07564,GA129715,Novel DNA based COVID-19 vaccine: A phase 1/1b trial for Australia,"This phase 1/1b clinical COVID-19 vaccine trial aims to assess the safety and immune responses of a candidate DNA vaccine made by Bionet-Asia.150 healthy volunteers aged 18 to 75 will be invited to participate. This is a partnership with 4 of Australia's most experienced academic vaccine trial sites, who form an Alliance, known as Vax4COVID and Bionet Asia. If successful larger phase 2 trials will follow. This trial is an important contribution to our goal of developing a COVID-19 vaccine.",2020,2022,University of Sydney,2307667.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +C07565,GA79778,COVID-19 Strategic Planning and Delivery of Testing,"This project consists of four key sub-projects that tackle the evolving pandemic, increase testing capability and control transmission of COVID-19. 1. 'One-step' nucleic acid detection that saves on critical lab consumables and is rapid. 2. Post-market evaluation of TGA approved diagnostic tests before to ensure the quality, accuracy and sensitivity. 3. Development of new testing protocols to enable more individuals to be tested. 4. Testing and validation of serological POCT and assays.",2020,2021,University of Melbourne,1781523.48,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07566,GA129717,A novel text mining and data linkage approach to investigate the mental health needs of the population during the COVID-19 period,"The impact of COVID-19 is expected to affect individuals with increases in mental illness, suicide, and self-harm events. The police are often the first to respond to these events, and their records contain valuable information that has not been used for mental health reporting purposes. This project will use a novel automated method to process police records of the last four years and investigate whether there have been any increases in mental illnesses before and during the COVID-19 crisis.",2020,2022,UNSW Sydney,164832.89,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07567,GA129716,Implementing Artificial Intelligence (AI) to enhance Lifeline's crisis support service capacity in response to COVID-19 and emerging crises,"Lifeline is Australia's national 24-hour crisis service for the general community. It featured heavily in the Australian Government's communications to encourage Australians to seek mental health support during COVID-19, with contacts surging 25 percent. This research aims to boost Lifeline's capacity by using artificial intelligence to enhance its ability to respond rapidly and effectively to emerging community mental health crises.",2020,2022,University of Canberra,154879.29,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07568,GA143639,Repurposing and re-optimising drugs that disrupt glycoprotein folding to treat COVID-19,"As of June 2020, COVID-19 has infected over 7.3 million people and killed over 413,000 in the six months since it emerged. It has pushed many healthcare systems and economies to breaking point. We recently discovered that a known drug is effective at stopping the virus under laboratory conditions. This research will determine exactly how the drug works, evaluate it's potential in pre-clinical models, and re-optimise the drug's antiviral properties to ensure that we can prevent future pandemics.",2021,2023,Walter and Eliza Hall Institute of Medical Research,989895.77,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C07569,GA85496,Reducing acute severe respiratory events in health care workers during the Covid-19 pandemic with OM85,"Covid-19 causes severe respiratory infection, leading to death in some. Health care workers are at high risk of infection. To protect health care workers we propose a clinical trial to reduce respiratory illnesses using a drug called OM85 that has been used safely in Europe for decades. We hypothesise that OM85 will protect health care workers from developing the most serious respiratory infections, saving lives and allowing them to safely treat patients.",2020,2021,University of Queensland,937713,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +C07570,GA137272,Australian understandings of infectious disease symptoms in the COVID era,"This project aims to study how Australians interpret symptoms of acute infectious diseases and how those beliefs shape their health-seeking behaviour. Using mixed social science methods, the project will document how Australians decide when to seek medical treatment at clinics or hospitals and when to stay at home, how they believe disease spreads and how they decide whether to go to work, school, social commitments, shops, or stay home when unwell, and what they think about government health policy regarding infectious disease in the wake of COVID-19. Humans spread diseases through culturally coded patterns of behaviour, and this project will offer critical public health insights in an era of infectious disease epidemics and pandemics.",2020,2023,Macquarie University,122056,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C07571,GA133346,Evaluating the effectiveness of lifestyle therapy versus standard psychotherapy for reducing depression in adults with COVID-19 related distress: The CALM trial,"The mental health of Australians has deteriorated since the COVID-19 outbreak. Our data show almost 1 in 2 Australians experienced depression during lockdown. CALM is an 8-week group-based, telehealth, lifestyle program for those with elevated psychological distress. It is delivered in Victoria as part of a partnership between Deakin University and Barwon Health's Mental Health, Drug and Alcohol Services. We anticipate CALM will be as effective and cost-effective as therapy for reducing depression.",2020,2022,Deakin University,628564.78,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Digital Health,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07572,GA143657,The Impact of the COVID-19 pandemic on Sexual and Reproductive Health Services and Outcomes in the Pacific Islands and Territories,"Delivery of sexual and reproductive health (SRH) services was curtailed in the Pacific Island countries and territories, as already limited resources were redistributed towards meeting priorities dictated by the COVID-19 pandemic. This project will investigate, analyse and quantify the impact on SRH outcomes. It will explore the experiences of SRH policy changes during the pandemic and aim to collaboratively develop a management plan for SRH programs should another pandemic occur in the future.",2021,2023,Burnet Institute,91329.55,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C07573,GA134286,Mobilising and empowering parents in the COVID-19 mental health response: A single-arm trial of an enhanced online parenting intervention to improve parent risk and protective factors for adolescent mental health,We aim to reduce the mental health impacts of COVID-19 and risk of longer-term adolescent mental health problems by enhancing their parents' ability to support them through this pandemic. We will involve parents in a co-designed process that learns and responds to their changing needs; to dynamically adapt an evidence-based parenting program integrated with an online peer-support network for parents. Our research will empower parents in their capacity to support their adolescents' mental health.,2020,2022,Monash University,427645.93,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Digital Health,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07574,GA85466,Tracking COVID-19 using genomics,Unknown,2020,2021,UNSW Sydney,2255680.1,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C07575,GA85461,The Australasian COVID-19 Trial (ASCOT),Unknown,2020,2023,University of Queensland,241500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III | Randomized Controlled Trial",Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,Clinical trials for disease management,2020 +C07576,GA82114,COVID-19 Prophylaxis with Hydroxychloroquine in Front-line Health and Allied-health Care Workers - The COVID-SHIELD Trial,Unknown,2020,2021,Walter and Eliza Hall Institute of Medical Research,2244000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +C07577,GA85465,Rapid Acceleration of the UQ COVID-19 Vaccine Program,Unknown,2020,2023,University of Queensland,2069993.1,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",,2020 +C07578,GA85474,Hyperimmune globulin: a rapid pathway to treatment of COVID-19,"We have assembled a partnership to rapidly harness the body's successful immune responses in the form of antibodies in the blood, to pool them from many patients, purify them and then use them as an intravenous therapeutic to bring the infection under control in those who have progressive infection.",2020,2021,UNSW Sydney,1425027.43,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C07579,GA134287,Narratives of Recovery - Practices supporting community mental health and well being post bush fires and COVID 19,Some communities have implemented their own strategies to address mental health problems following COVID19. Local responses to community need are grounded in contextual knowledge and use existing resources. This project will investigate two different interventions delivered on the South Coast of NSW. The research will provide evidence about ways the interventions ameliorated crises. The outcomes will include recommendations for place-based. culturally safe approaches to mental health care.,2020,2022,University of Wollongong,298062.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C07580,GA82108,Molecular Clamp Stabilized Spike Vaccine for Rapid Response,The Molecular Clamp platform is Australia's most advanced COVID-19 vaccine program. The strategic partners leading this program are aiming to validate safety and efficacy to support development and scale-up of the vaccine for further clinical and potential emergency distribution. The proposed work will identify correlates of protection from infected patients and compare with immune responses elicited by the candidate vaccine. This information will support vaccine dose and adjuvant selection.,2020,2021,University of Queensland,1336470.78,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07581,GA143686,Improving epidemiological assessment for the prevention of travel-related infectious diseases,"Understanding the epidemiology and healthcare burden of travel-related infections is important in order to improve the provision of pre-travel preventive healthcare in Australian travellers. Exploring the impact of the COVID-19 pandemic on perceptions of travel-related risks, attitudes towards travel, and pre-travel preventive health seeking behaviour is also critical to improve the provision of safe travel advice and optimise pre-travel preparation among Australian travellers.",2021,2024,Monash University,99557.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Approaches to public health interventions,2021 +C07582,GA79788,Transforming recognition and assessment of COVID-19 in Australia using lung CT,Unknown,2020,2021,University of Sydney,688180.68,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C07583,GA85460,Stem cell-derived human tissue models for the identification of drugs to treat COVID-19,Unknown,2020,2021,University of Melbourne,420900,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +C07584,GA121377,Re COVER ing SME's Townsville,"This employment project will tailor small business recruitment of a person to suit a very detailed match with a candidate. The project will be delivered in accordance with current departmental guidelines as impacted by the COVID-19 pandemic. The simple goal is that 20 SME's will be taught how to access all types of training and support from all different avenues to ensure the safe and valuable recruitment of a new worker. This also means 20 unemployed people will gain long term sustainable employment and these employer/employee relationships and the further development of them will be provided by this project, ensuring 20 long term employment outcomes.",2020,2021,Employment Solutions Global Inc,51081.84,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07585,GA79142,Melbourne's Northern Economic Wedge,"The project will conduct a quick but comprehensive environmental scan of employers in Melbourne’s North West region, with a focus on identified sectors that provide essential products and services in the current environment, to determine the number and range of occupations where there is urgent demand. It will then facilitate the listing of these positions on key job sites such as MNJoblink, Australian Government’s Jobs Hub and Working for Victoria, to provide opportunities for the multiples of people that have ceased employment or have been stood down as a result of Covid â€"" 19.",2020,2020,Federation University Australia,35178,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07586,GA77615-V1,YE Agenda Limited,"The Machinery Partnerships Transition to Work (TTW) project presents a unique opportunity for at-risk and disengaged young people to participate in a new and innovative aptitude-focussed skills development program. Participants will undertake all activities online through a dedicated RET project website www.machinerypartnerships.com.au which includes a link to stage 1 of a competency-based training progam. The Bridging the skills shortage in the Northern Inland - heavy machinery operators project is already producing exciting results. These include traditional aptitude assessment blended with game-based simulation, and introductions to employers resulting in participants being invited to apply for jobs. Due to COVID-19 restrictions, all elements have been adapted for online delivery. This proposal seeks to capitalise on these early outcomes and engage a cohort of TTW candidates (16-18 year olds) in an entry-level skills online development and training initiative, specially designed for this cohort.",2020,2021,Ye Agenda Limited,42846.38,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07587,GA75956-V1,Federation University Australia,"The program is focused on those mature age jobseekers who present with a range of barriers to employment and require intensive assistance if they are to become work ready. They will often, although not always, be long-term unemployed and likely present with a complex array of personal and social circumstances requiring intensive support. The target group will be qualitatively different from the typical client going through the Career Assistance Program for jobseekers aged over 45, targeting those requiring significant additional assistance to that focused on transferable skills and the better targeting of job-search provided via Call To Action. In order to improve clients’ digital literacy, and in response COVID-19, the program will be delivered entirely online. It adds significant value by being designed as an action research project to identify this jobseeker cohort’s barriers and needs and learnings to be applied to improving the delivery of the program in real time and that can inform the development of future, similar, programs.",2020,2021,Federation University Australia,53529.91,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C07719,173702,Canadian International COVID-19 Surveillance Border Study,"In early September 2020, McMaster HealthLabs launched a month-long study to test arriving international passengers at Toronto's Pearson International Airport for COVID-19. The study was supported by Air Canada and the Greater Toronto Airport Authority. The study assessed the feasibility of enrolling arriving passengers, the acceptability and quality of self-collected specimens for detection of COVID-19 infection, and the scale-up of robotic testing for time-efficient and cost-effective COVID-19 testing. Participants self-collected specimens at the airport on arrival, and weekly at home during 14 days of quarantine. Current data as of September 30, 2020 demonstrated the feasibility for a robust and cost-effective COVID-19 surveillance program for arriving passengers using self-collection, with enrollment of ~8,000 passengers and collection of ~13,000 specimens. COVID-19 results were available within 12-24 hours, and SARS-CoV-2 virus was detected in ~1% of passengers. In the current study proposal, we will expand study enrollment for a further 4-6 weeks, to complete 14-day follow-up on 10,000 passengers. We will add additional resources to regularly contact participants by email or telephone, in order to improve adherence with specimen collection, completion of questionnaires, and to better assess compliance with quarantine. Our study will provide important data on COVID-19 infection on arrival, the development of infection during 14-days of quarantine, and compliance with quarantine. These data will inform policy for quarantine requirements, while demonstrating the feasibility of incorporating passenger testing into decision-making algorithms for travelers arriving in Canada.",2020,2021,McMaster University,1875000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities,2020 +C07720,173622,Canadian Immunization Research Network: COVID-19 Vaccine Readiness,"The Canadian Immunization Research Network (CIRN) is a collaborative national research network that brings together more than 150 investigators in 56 institutions across Canada. CIRN comprises eight subnetworks built to provide research capacity that is responsive and scalable to undertake research during an infectious disease crisis such as a pandemic and to provide public health with Canadian-relevant vaccine-related research for public health decision making. As a network of networks, CIRN is centered on clinical research, surveillance and epidemiological research, and public health program evaluation. The eight subnetworks are the Clinical Trials Network (CTN), Serious Outcomes Surveillance Network (SOS), Canadian National Vaccine Safety Network (CANVAS), Special Immunization Clinics Network (SIC), Provincial Collaborative Network (PCN), Reference Laboratory Network (RLN), Modeling and Economics Research Network (ModERN), and Social Sciences and Humanities Network (SSHN). Four research areas will be addressed: COVID-19 vaccine clinical trials, population prioritization and modeling, vaccine hesitancy and uptake, and coordination and information sharing. The COVID-19 vaccine clinical trials research area will be met by coordinating research through the CTN, RLN, SIC, CANVAS, and PCN networks. The population prioritization and modeling research area will be met by assessing various models through the ModERN network. The SSHN network will address the vaccine hesitancy and uptake research area. Coordination and information sharing will be addressed by the collaborative efforts of the Network Management Office, which will work with network leaders in order to coproduce knowledge that will inform our stakeholders and public health.",2020,2022,Dalhousie University,1520000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Health Canada,Canada | United Kingdom,Americas | Europe,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2020 +C07763,02L18A700,Using good solutions for the future - COVID-19 Lessons Learned / Gute Lösungen für die Zukunft nutzen - COVID-19 Lessons Learned,"The rapid spread of the coronavirus SARS-CoV-2 and the accompanying measures to reduce the reproduction rate have a strong impact on international and national social life. The working environment has also to comply with strict and changing regulations and measures to protect health and is thus confronted with contact restrictions and distance rules as well as partially broken supply chains. In order to be able to continue working and to provide the services necessary to maintain social life, many companies and organizations have had to make far-reaching adjustments to their work structures and processes at short notice, some of which did not seem feasible or sensible before the pandemic. The aim of the research project COVID19LL is to determine which measures can also be applied successfully in a post-pandemic period and gain currency. Based on an exemplary field analysis of the change and transformation processes, best practices are to be identified, described and evaluated across sectors and regions. The research results should provide information about positive changes during the COVID-19 pandemic that can be established in a future working world in the medium and long run and can also be transferred across sectors.",2020,2021,"Technical University of Munich, Munich / Technische Universität München, München",299353.3,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07764,01KX2022A,MODUS-COVID: Model-based investigation of school closures and other measures to mitigate Covid-19 - Subproject 1: Urban and regional simulation based on data-driven synthetic movement profiles,"The spread of SARS-CoV-2 poses considerable problems for the world, including Germany. As is well known, extensive restrictions on normal life have been decided to avert an overload of the health system. In this cooperation between Technische Universität Berlin (Prof. Nagel, Department of Transport System Planning and Telematics), the Humboldt University of Berlin (Prof. Brockmann, Institute for Theoretical Biology) and the Free University of Berlin (Prof. Schütte, Zuse Institute Berlin) complex model applications are used to investigate the infection dynamics in an urban, regional and nationwide context. The overall goal of the MODUS-COVID joint project is to investigate the effects of non-pharmaceutical interventions (NPIs) on the infection dynamics of SARS-CoV-2, with at least initially a special focus on school closings. The project also aims to improve the understanding of infection chains and the dynamics of spread within urban areas as well as in a regional and nationwide context. In addition to examining school closings, other measures and combinations of measures to curb the spread of SARS-CoV-2 are examined and model-based policy recommendations are formulated. The aim of MODUS-COVID - subproject 1 is the extension of a mesoscopic traffic simulation to simulate infection dynamics, the testing and processing of sub-contracted mobile data-based movement patterns, as well as the implementation of measures within the activity and traffic model.",2020,2021,Technische Universität Berlin,702333.3,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C07765,01KX2022B,MODUS-COVID: Model-based investigation of school closures and other measures to mitigate Covid-19 - Subproject 2: Supraregional infection dynamics and analysis of infection graphs,"The spread of SARS-CoV-2 poses considerable problems for the world, including Germany. As is well known, extensive restrictions on normal life have been decided to avert an overload of the health system. In this cooperation between Technische Universität Berlin (Prof. Nagel, Department of Transport System Planning and Telematics), the Humboldt University of Berlin (Prof. Brockmann, Institute for Theoretical Biology) and the Free University of Berlin (Prof. Schütte, Zuse Institute Berlin) complex model applications are used to investigate the infection dynamics in an urban, regional and nationwide context. The overall goal of the MODUS-COVID joint project is to investigate the effects of non-pharmaceutical interventions (NPIs) on the infection dynamics of SARS-CoV-2, with at least initially a special focus on school closings. The project also aims to improve the understanding of infection chains and the dynamics of spread within urban areas as well as in a regional and nationwide context. In addition to examining school closings, other measures and combinations of measures to curb the spread of SARS-CoV-2 are examined and model-based policy recommendations are formulated. The aim of MODUS-COVID - subproject 2 is the integration of more complex infection models based on previous work, the expansion of the simulation methodology to include national infection mechanisms, and the analysis of the dynamic infection graph for specific measures.",2020,2021,Humboldt-Universität zu Berlin,151494.26,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C07766,01KX2022C,"MODUS-COVID: Model-based investigation of school closures and other measures to mitigate Covid-19 - Subproject 3: Parameter estimates, detailed infection dynamics, and high performance computing","The spread of SARS-CoV-2 poses considerable problems for the world, including Germany. As is well known, extensive restrictions on normal life have been decided to avert an overload of the health system. In this cooperation between Technische Universität Berlin (Prof. Nagel, Department of Transport System Planning and Telematics), the Humboldt University of Berlin (Prof. Brockmann, Institute for Theoretical Biology) and the Free University of Berlin (Prof. Schütte, Zuse Institute Berlin) complex model applications are used to investigate the infection dynamics in an urban, regional and nationwide context. The overall goal of the MODUS-COVID joint project is to investigate the effects of non-pharmaceutical interventions (NPIs) on the infection dynamics of SARS-CoV-2, with at least initially a special focus on school closings. The project also aims to improve the understanding of infection chains and the dynamics of spread within urban areas as well as in a regional and nationwide context. In addition to examining school closings, other measures and combinations of measures to curb the spread of SARS-CoV-2 are examined and model-based policy recommendations are formulated. The aim of MODUS-COVID - subproject 3 is to extend the simulation methodology to include more complex infection models, determine infection parameters based on empirical data, transfer the parameterizations to the model, and provide a high-performance computing infrastructure for run infection simulations.",2020,2021,Konrad-Zuse-Zentrum für Informationstechnik Berlin (ZIB),250870.82,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C07767,01KX2023,Simulation-based decision support in the COVID-19 pandemic,"The simulation of the spread of infectious diseases is an important tool which can be used to plan required resources and intervention strategies. The researchers have develpoed the COVID-19 pandemic simulation tool CovidSIM which will be extended in this project in order to help answering urgent questions regarding optimal intervention strategies and the corresponding exist strategies. This work will be accompanied by literature studies and data evaluation to provide realisistc simulation settings. Most importantly, the project aims for the simulation of real-world scenarios and a timely communication of their input and output with stakeholders and decision makers.",2020,2021,Regierungspräsidium Stuttgart,358793.14,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Impact/ effectiveness of control measures,2020 +C07768,01KX2021,National Research Network of the University Medicine on Covid-19 (Nationales Forschungsnetzwerk der Universitätsmedizin zu Covid-19),"The aim of the network is to bring together and evaluate action plans, diagnostic and treatment strategies from all German university hospitals. This bundling of competencies and resources is intended to create structures and processes in the inics that ensure the best possible care for people with COVID-19. The university clinics and the other hospitals will then be able to act quickly, with quality assurance and effectively. https://www.netzwerk-universitaetsmedizin.de/projekte The program is geared towards rapid and immediate supportive effects in order to optimally care for patients suffering from Covid-19. A strong emphasis is placed on research and health services research close to the clinic, the results of which, according to the translational approach, should flow directly into or support the health care process or crisis management. In addition, if possible, sustainable structures should be established that will also develop effectiveness in future cooperation beyond the project. The ""Network University Medicine"" promotes the systematic and comprehensive exchange between the cooperation partners in order to achieve a common approach to fighting pandemics through joint developments in research and patient care, evidence-based procedures and mutual learning. The creation of this structure also serves the goal of being able to face future crisis situations faster, more effectively and better prepared. All of this can save lives in health crises like the current coronavirus pandemic.",2020,2020,Charité Universitätsmedizin Berlin,163061149.7,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management | Health Systems Research | Research on Capacity Strengthening,"Supportive care, processes of care and management | Health service delivery | Health leadership and governance | Institutional level capacity strengthening | Systemic/environmental components of capacity strengthening",2020 +C07769,01IS20S04,Software Sprint - Single project: quarano - Digital documentation of COVID-19 infection cases & contact persons for health authorities,"In the quarano project, a platform will be created to support health authorities in documenting isolation and quarantine measures as well as in manual contact tracing of index patients. By digitizing self-reports of confirmed COVID-19 cases, data currently collected manually will thus be made available to health authorities automatically and in real time. More time is left (even with increasing case numbers) for the critical and meaningful cases. A simple and fast implementation (web-based roll-out and cloud hosting) allows for quick relief. By providing information about direct contacts of the infection case (RKI category I and III), they can be directly informed and collected. Via an interface, the health authorities should be able to directly see which contacts have been indicated and, if necessary, need to be contacted. This tracking and documentation of clusters / chains of infection by the health authorities is already a central point of national epidemic management - and will become even more important with the relaxation of the measures.",2020,2020,"Thorsten Heilig, Ferdinand Biere, Ulrich Kolzenburg und Bodo Biere GbR c/o Ferdinand Biere",52245.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Data Management and Data Sharing | Digital Health,,,Germany,Germany,Epidemiological studies | Health Systems Research,Disease surveillance & mapping | Health information systems,2020 +C07770,01IS20S16,Software Sprint - Single project: Dark figure radar - we shed light on the dark figure of COVID-19.,"The project ""DunkelzifferRadar"" aims to shed light on the dark figure of COVID infections. The core idea is to collect and combine user-specific data with established sources to estimate unregistered cases of infection using various calculation models. The ""dark figure"" is to be visualized in a user-friendly and easily understandable way and made available to the users.",2020,2020,Paul Thum Meyer Schaller Hämmerl GbR,47648.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease surveillance & mapping,2020 +C07771,01IS20S28,Software Sprint - Single project: OpenResearch - Open Research on COVID19,"The plan is to develop a modular, extensible & open API platform that will provide AI services to extract insights & information from the large number of scientific writings on COVID-19. During the grant period, 3 AI services based on Topic Modeling, Doc2Vec & Q&A with SQuAD+Bert will be developed. The combination of these provides a summary & enables semantically rich queries on the scientific content. The API platform integrates with dashboards, websites & 3rd party platforms. The goal is not only to offer insight into the data, but also to allow users to train their own data models. Although COVID-19 is a new disease, already more than 52,000 wiss. Publications have been written on this & more are being added daily. Doctors, physicians & researchers do not have the time to read all the scientific publications, especially if they are in front of a scientific meeting. Publications, especially when they are faced with solving a specific problem, which is not the main topic of the essays, but the solution is contained in them. Helping healthcare professionals cope with the complexity of large volumes of scientific material & enabling them to perform user-friendly data retrieval using NLP techniques are critical attributes for increasing response effectiveness to current & future challenges.",2020,2020,"OpenResearchCOVID19 - Leonardo de Araújo, Nina Hentschel & Hanna Blonska GbR",52119.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Data Management and Data Sharing,,,Germany,Germany,Health Systems Research,Health information systems,2020 +C07772,02WRS1557A-C,Wastewater epidemiology using SARS-CoV-2 as an example biomarker to assess COVID-19 infections at a population scale (Biomarker CoV2),"In the recent past, there is increasing interest in using wastewater-based epidemiology (WBE) as a diagnostic tool to assess the consumption of illicit drugs and pharmaceuticals across an entire sewershed. In the ongoing pandemic, even SARS-CoV-2 could be used as a biomarker as part of WBE to detect not only early changes in the infection pattern, to estimate the number of COVID-19 infected people with asymptomic effects, but also to assess the overall infection pattern in a community including the efficacy of counter measures. The main goals of this study are a) the development of quantitative methods for the identification of SARS-CoV-2 and other viruses in raw sewage, b) a comprehensive assessment of the infection pattern at a population level using WBE based on a novel SARS-CoV-2 biomarker model, c) the development and validation of strategies to identify local infection hot spots in a community, d) the exact assessment and prediction of COVID-19 infections in a community based on the presence of enveloped viruses in municipal wastewater, as well as e) the transfer of the developed strategy and biomarker model to other pathogenic viruses. The overarching hypothesis of this study is that the quantification of SARSCoV- 2 as a biomarker in raw sewage enables the exact assessment and prediction of COVID-19 infections at the population level in a given community. The developed WBE strategy will be expanded to other pathogenic viruses. In addition, based on the developed WBE strategy we will provide guidance regarding appropriate sampling strategies, analysis and the assessment of positive results for wastewater treatment plant operators, health officials, and local decision makers.",2020,2022,"Technical University of Munich, Chair of Urban Water Systems Engineering",634937.94,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics,2020 +C07773,03COV01A,CORONA - SARS-CoV-2-VLP-IVD - Development of a certified in vitro diagnostic (IVD) for the reliable determination of COVID-19-specific immune responses in human serum; subproject 1: Production and characterization of SARS-CoV-2-specific antibodies.,"In the SARS-CoV-2-VLP-IVD project, the partners will jointly establish a reliable and CE-certified diagnostic based on SARS-CoV-2 virus-like particles (VLPs) for the determination of human immune status. The Chair of Immunotechnology at the University of Potsdam will produce camelid antibody formats and provide the tools for affinity chromatographic purification. In addition, human antibodies will be produced that can be used as positive reference materials in the test system.",2020,2021,Universität Potsdam,144598.18,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07774,03COV01B,CORONA - SARS-CoV-2-VLP-IVD - Development of a certified in vitro diagnostic (IVD) for the reliable determination of COVID-19-specific immune responses in human serum; subproject 2: Design and production of virus-like particles (VLPs).,"Within the scope of the subproject, high-quality virus-like particles (VLPs) will be produced. For this purpose, a stable-transfected cell line will be developed. An innovative plasmid design strategy will be applied, which already contain relevant mutations of the virus (antigenicity). The special feature here is that the production design is set up in such a way that all steps (except for the one-time lentiviral transfection) do not require an increased safety level (everything below S1). Mass production is carried out at an external partner under the supervision of Dr. Stefan Hirschberg.",2020,2021,Charité - Universitätsmedizin Berlin,134832.68,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07775,03COV01C,CORONA - SARS-CoV-2-VLP-IVD - Development of a certified in vitro diagnostic (IVD) for the reliable determination of COVID-19-specific immune responses in human serum; subproject 3: Development of a routine method for the concentration and purification of SARS-CoV-2 VLPs.,"The objectives for the collaborative partner sifin are to build a chromotography column based on the principle of immunoaffinity for the purification of virus particles (VLPs). For the purification of the recombinantly produced VLPs, specific camelid antibodies provided by the partner University of Potsdam will be used. The focus of the first project phase is the characterization and validation of the available antibodies with respect to the intended application. An important interim goal is the identification of suitable conditions for the stable binding of the antibodies to the column matrix while maintaining their functionality as VLP scavengers. Further, optimal conditions for antigen-antibody binding in the column and finally the largely non-destructive elution of the VLPs from the column will be determined. The final phase of the project will be the transfer of the cell lines from the partners and the upscaling of the production of culture supernatants and antibodies with the aim of transferring the production of the raw materials to an industrial scale.",2020,2021,sifin diagnostics gmbh,175009.43,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C07776,03COV01D,CORONA - SARS-CoV-2-VLP-IVD - Development of a certified in vitro diagnostic (IVD) for the reliable determination of COVID-19-specific immune responses in human serum; subproject 4: Development and validation of a SARS-CoV-2-VLP ELISA and certification as an in vitro diagnostic (IVD).,"CellTrend will develop and validate a SARS-COV2-VLP ELISA as part of the project. Based on the data obtained, the IvD will then be approved. It is the goal of the project to develop a stable, robust and practical immunoassay for use in a routine laboratory. The technical target parameters for the SARS-COV2-VLP ELISA are 99.5% sensitivity and 99.5% specificity. Due to the unchanged pandemic situation, production capacities of 400,000 kits/month will be established.",2020,2021,CellTrend Gesellschaft mit beschränkter Haftung,162113.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C07777,03COV01E,"CORONA - SARS-CoV-2-VLP-IVD - Development of a certified in vitro diagnostic (IVD) for the reliable determination of COVID-19-specific immune responses in human serum; subproject 5: Establishment of a biobank, comparative measurements and preparation of international distribution","Within the scope of the subproject, a biobank with well-characterized samples is to be established and ultimately international distribution is to be undertaken. By linking Wimedko to MeoClinik - Berlin's largest private practice with 40,000 patients per year - approximately 6,000 serum samples will be collected and archived for test development, validation and approval. The serum samples will be analyzed in-house with EuroImmun's ELISA kit and compared with the results of the new Roche test (Berlin laboratory). The final step is the joint validation and approval study of the newly developed VLP ELISA with CellTrend. Dr. Julian Kamhieh-Milz and Dr. Omar Kamal have a broad network at their disposal, through which the international distribution of the final product can be realized.",2020,2021,Wimedko GmbH,155693.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07778,03COV02A,"CORONA - NuForm - Proximity despite distance - new forms of encounter communication in museum space; subproject 1: Design paradigm, visitor journey, platform strategy.","Encounter communication in museums, visitor centers, show rooms, cultural institutions or at exhibitions/fairs is inherently linked to spatio-temporal contact - with staff, exhibits, other visitors. Hygiene requirements, distance rules and visitor/travel restrictions in a corona context therefore create special challenges for encounter communication. The NuForm project is specifically looking for approaches and options that are not merely acutely effective in relation to the crisis, but for measures that have potential for sustainable benefits for visitors and operators of encounter communication that extend beyond the crisis. In some cases, completely new solutions must be designed and implemented, and the process of digital transformation must be accelerated significantly. Using the example of museum visits under pandemic conditions, the project will investigate which factors play a decisive role in encounter communication, how individual factors can be substituted or overcompensated for with digital and virtual means, and which new possibilities can arise from a hybridization of real and virtual offerings. In particular, contactless and hygienic forms of interaction will be considered, as well as concepts for virtual visits, for the intersection of real and virtual encounters, for personalized visitor guidance, and for the expansion of the museum space. The two partners of the research program approach these questions from two different perspectives. For Art+COM, the focus is on the conceptual approach and the technical solutions, application possibilities and innovations.",2021,2022,ART + COM AG,609541.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C07779,03COV02B,"CORONA - NuForm - Proximity despite distance - new forms of encounter communication in museum space; subproject 2: Visitor behavior, formats and indicators (of knowledge transfer).","Encounter communication in museums, visitor centers, show rooms, cultural institutions or at exhibitions/fairs is inherently linked to spatio-temporal contact - with staff, exhibits, other visitors. Hygiene requirements, distance rules and visitor/travel restrictions in a corona context therefore create special challenges for encounter communication. The NuForm project is specifically looking for approaches and options that are not merely acutely effective in relation to the crisis, but for measures that have potential for sustainable benefits for visitors and operators of encounter communication that extend beyond the crisis. In some cases, completely new solutions must be designed and implemented, and the process of digital transformation must be accelerated significantly. Using the example of museum visits under pandemic conditions, the project will investigate which factors play a decisive role in encounter communication, how individual factors can be substituted or overcompensated for with digital and virtual means, and which new possibilities can arise from a hybridization of real and virtual offerings. In particular, contactless and hygienic forms of interaction will be considered, as well as concepts for virtual visits, for the intersection of real and virtual encounters, for personalized visitor guidance, and for the expansion of the museum space. The two partners in the research program are approaching these questions from two different perspectives. The Museum für Naturkunde is investigating the factors and effects of different communication formats along a gradient from real to virtual with regard to visitor behavior and addressing different sub-publics.",2021,2022,Museum für Naturkunde Leibniz-Institut für Evolutions- und Biodiversitätsforschung (MfN),609541.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C07780,03COV03A,CORONA - QURATOR - PANQURA - a technology platform for more information transparency in times of crisis; subproject 1: AI-supported personalized search according to the social-linked data principle in transparent and verified sources.,"The goal of 3pc's subproject within the PANQURA joint project is the development of software for AI-supported personalized search based on the social-linked data principle in transparent and verified sources. Thus, 3pc offers a novel solution approach for two application areas that are to be combined in one software: - AI-based online search: real-time search in dynamic online sources (information streams) with novel user interfaces for semantic search functionalities and transparent search algorithms - Personalization: processing and storage of personal contextual information in a decentralized network (SOLID) with special consideration of the users' privacy.",2021,2022,3pc GmbH Neue Kommunikation,969424.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2021 +C07781,03COV03C,"CORONA - QURATOR - PANQURA - a technology platform for more information transparency in times of crisis; subproject 3: Validation of sources, content, facts.","The current Corona pandemic has shown that with the emergence of a crisis, an overflowing amount of information is published on effects, affected persons, regulations, medications and measures, the truthfulness and relevance of which is difficult to assess. This is also due to the fact that various forums with diverging opinions are formed on the emerging issues, for which there are neither established reliable sources nor a recognized circle of experts available. As a result, in the media and many other fields, time-consuming, manual analyses are increasingly being carried out to examine and evaluate information from the web and social media before it is used or further published. Against this background, Condat is researching and developing new services for the analysis and validation of sources, content, and facts based on AI and Semantic Web technologies in the present subproject, with which users can evaluate information from the Web more quickly and reliably.",2021,2022,Condat Aktiengesellschaft,613553.28,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2021 +C07782,03COV03D,CORONA - QURATOR - PANQURA - a technology platform for more information transparency in times of crisis; subproject 4: AI-assisted provision of pandemic-related information in process contexts.,"The current COVID 19 crisis shows that transparency and objectivity are key to managing a pandemic that poses unprecedented challenges to governments and societies worldwide. The targeted spread of misinformation or fraudulent offers of help further complicates this situation. The overall objective of the joint project is to meet this particular challenge with a decentralized technology platform for greater information transparency. It is aimed at citizens as well as experts from science and the media. The platform provides experts with AI-based tools for researching and evaluating pandemic-related information. They contribute to making secured knowledge and reputable information offers visible via the platform. At the same time, they can make transparent the criteria they use to evaluate information sources. The sub-project applied for here is aimed primarily at two target groups: on the one hand, citizens in their role as private individuals and, on the other hand, companies and other organizations whose business processes are affected by the pandemic. In the context of citizen information, the sub-project is intended to contribute to the more efficient transport of relevant information on the one hand and to enable an evaluation of the reliability of the information provided on the other. Companies should be given the opportunity to contextualize their processes with current pandemic information and also its reliability in order to be able to decide as early as possible on any necessary process adjustments.",2021,2022,Semtation GmbH,154077.83,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2021 +C07783,03COV03E,CORONA - QURATOR - PANQURA - a technology platform for more information transparency in times of crisis; subproject 5: AI technologies for personalized curation of online articles to ensure information transparency in times of crisis.,"The COVID 19 crisis shows that transparency and objectivity are the keys to overcoming a pandemic that poses unprecedented challenges to governments and societies worldwide. This is particularly true for European democracies, which are based on the dignity and freedom of the individual. Only well-informed citizens can bear the necessary compromises in democratic processes, which are demanded of the individual in times of crisis. At the same time, the digital flood of information and the confusion of sources pose challenges for every individual. The targeted dissemination of false information or fraudulent offers further complicates the situation. The aim of the joint project is to meet this particular challenge with a technology platform for more information transparency. The platform provides AI-based tools for researching and evaluating pandemic-related information. They contribute to making reliable knowledge and serious information offers visible in a transparent form. The DFKI subproject will deal with the automatic analysis of online contributions, the presentation of results and the personalization of information access.",2021,2022,Deutsches Forschungszentrum für Künstliche Intelligenz GmbH,606829.98,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Innovation,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2021 +C07784,03COV03F,"CORONA - QURATOR - PANQURA - a technology platform for more information transparency in times of crisis; subproject 6: Aspect-oriented knowledge analysis and context-sensitive, explorative information search.","The goal of the subcomplex ""Aspect-Oriented Knowledge Analysis"" is to develop a semi-automatic procedure for recognizing contexts in which formalized knowledge (facts and axioms) are valid. E.g., the proposition ""wearing a mouth guard does not provide substantial protection against transmission of the Corona virus"" expressed in online sources does not represent an objectively true fact but a proposition that arose and may be refuted in the context of specific scientific research activities. Context is important to objectify facts, allow end users to categorize and evaluate information, and resolve filter bubbles. Context can be the scientific source, but it can also be temporal, geographic, political, religious, and so on. The second complex ""context-sensitive exploratory information search"" builds on the first using learned contexts formalized in AspectOWL as additional input for a semantic search. The goal is to sort the search results according to the user's needs, taking context into account, and to present the context in a suitable way to explain and classify the search results for the user.",2021,2022,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,621422.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Policies for public health, disease control & community resilience",Communication,2021 +C07785,03COV04,CORONA - CORONAmem - Molecular determinants of differential host susceptibility to SARS-CoV-2 at the point of entry.,"This project will contribute to the management of the corona crisis. One of the most striking features of the Covid 19 outbreak is the tremendous variation in individual susceptibility to the virus. Coronaviruses gain access by binding host membrane proteins via the viral membrane envelope spike protein (S protein). Therefore, the interaction of the S protein with the host cell represents a Trojan horse to enable viral infection. One goal of this proposal is to characterize the interactions of the S protein with genetic variants of host membrane proteins, both structurally and biophysically. The knowledge gained will allow us to better understand why individuals respond so differently to the virus. This may allow classification of at-risk patients and pave the way for personalized therapies. Since the lipid composition of the host cell is dependent on the tissue as well as the age, dietary habits and previous diseases of the host, studies on the dependence of membrane binding of the spike protein on lipid composition should provide insights into why certain populations are more susceptible to infection with SARS-CoV-2, regardless of their genetic background. Therefore, r the interactions of the S protein with model membranes should be investigated to analyze the influence of lipid composition on protein-membrane interactions.",2021,2023,Martin-Luther-Universität Halle-Wittenberg,2140583.57,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2021 +C07786,03COV06A,CORONA - PlasmaplusCorona - Plasma-based respiratory tract disinfection to reduce SARSCoV-2 viral load in vitro and in vivo; subproject 1,"The SARS-COVID2 pandemic has highlighted how susceptible humans are to new corona viruses and the respiratory and systemic diseases that accompany them. In the body, the virus spreads to the lungs and throat. These reservoirs are also instrumental in determining how the virus spreads through the respiratory system, allowing the virus to infect others. A reduction of the viral load in the pharynx and lungs could therefore contribute significantly to reducing infectivity and possibly the severity of the course of the disease. In the sub-project ""PlasmaplusCorona-INP"" (PPC-INP), a new technology is being explored in this context, which is based on the physical cold plasma process and is being investigated in two different approaches. In the first approach, a plasma jet technology is developed and optimized, which is expected to be suitable for application in the pharynx. In the second approach, plasma-treated air or a plasma-treated air-aerosol mixture will be designed for use as an inhalation gas to reduce the viral load in the lungs. In this subproject, the planning, design, characterization and optimization of the physical plasma processes will be carried out. Furthermore, both processes will be tested in vitro for their antiviral and antimicrobial efficacy in the subproject PPC-INP. In addition, cytotoxicity and genotoxicity tests are carried out in vitro.",2021,2024,Leibniz-Institut für Plasmaforschung und Technologie e.V.,1415324.99,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C07787,03COV06B,CORONA - PlasmaplusCorona - Plasma-based respiratory tract disinfection to reduce SARSCoV-2 viral load in vitro and in vivo; subproject 2,"The current coronavirus pandemic demonstrates once again that zoonotic viruses can cross species boundaries at any time and spread from animals to humans. Several years may pass before a suitable vaccine against the new pandemic virus is available. Therefore, until a vaccine is widely available, it is of utmost importance and urgency to develop appropriate therapeutic interventions that will significantly reduce viral load and thus contribute to reduced overall mortality. In these experimental projects, the highly innovative plasma technology for viral load reduction by respiratory tract disinfection will be evaluated for its potential therapeutic use against covid-19. The preclinical evaluation of plasma therapy against Covid-19 will be performed in a suitable animal model (hamster), which reflects the clinical findings very well. Here, potential toxicities of different plasma sources will first be investigated in the hamster model and non-toxic treatment protocols will be determined accordingly. Subsequently, SARS-CoV-2 infected animals will be treated orally and inhalatively with different plasma sources using established protocols and their efficacy in reducing the viral load in the respiratory tract will be determined. The results from this experimental project will lead the way for the development of new plasma-based therapies against infections.",2021,2024,"Heinrich-Pette-Institut, Leibniz-Institut für Experimentelle Virologie",836911.89,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C07788,03COV06C,CORONA - PlasmaplusCorona - Plasma-based respiratory tract disinfection to reduce SARSCoV-2 viral load in vitro and in vivo; subproject 3,"The SARS-CoV-2 pandemic has overwhelmed healthcare systems worldwide. To date, there are neither effective treatments nor vaccines. Therefore, innovative strategies to combat SARS-CoV-2 infection and concomitant opportunistic respiratory pathogens are urgently needed, especially in artificially ventilated patients. In the body, the virus spreads from the throat to the lungs and other organs and can infect others via aerosols. The PPC strategy is to reduce the viral load and accompanying pathogens in the respiratory tract using cold atmospheric pressure plasma (CAP) or ventilation air or aerosols treated with it. To investigate this therapeutic use of CAP, we are using air-liquid interface (ALI) culture of airway epithelial cells in the PlasmaplusCorona-FZB (PPC-FZB) subproject to analyze I) the anti-infective effect of CAP against coronaviruses (including SARS-CoV-2), bacterial and fungal pathogens, and II) the toxic and inflammatory response of the epithelial cells. The opportunistic bacteria and fungi studied in this work are particularly problematic in ventilator patients and difficult to treat due to increasing antibiotic resistance. Our studies on the effect of CAP in the ALI model against SARS-CoV-2 and other respiratory pathogens will serve to optimize this new therapeutic medical technology before it is tested in experimental animals and used in the clinic.",2021,2024,Forschungszentrum Borstel Leibniz Lungenzentrum,353046.21,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2021 +C07789,03COV07,CORONA - ICROVID - Identification of cardiovascular and molecular prognostic factors for morbidity and mortality in COVID-19 sepsis.,"This project aims to make a significant contribution to the management of the COVID-19 crisis by investigating clinical and molecular mechanisms of COVID-19 disease in the acute phase and in the further course - with a focus on cardiovascular events. In the clinical picture of sepsis, also known as blood poisoning, a dysregulated host response of the body to an infection leads to life-threatening organ failure. Sepsis can also occur in severe cases of the disease ""Coronavirus Disease-2019 (COVID-19)"" caused by the virus SARS-CoV-2. In particular, there is evidence that there is an increased incidence of cardiovascular complications with COVID-19. These include impaired cardiac output, damage to the inner vessel walls, and thromboembolic events. A multicenter prospective cohort study in German ICUs is planned to identify cardiovascular and molecular prognostic factors for mid-term disease severity and mortality after COVID-19-associated sepsis. A comprehensive clinical evaluation focusing on the cardiovascular system will be complemented by high-dimensional laboratory chemical and molecular biology analyses of biomaterials. The scientific work is expected to contribute to the elucidation of pathophysiology in severe COVID-19 courses and thus provide a basis for the development of targeted personalized therapies.",2021,2023,Jena University Hospital,2965258.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C07790,03COV08,CORONA - INFLIXCOVID - Phase 2 study evaluating infliximab in patients with severe COVID-19 progression.,"This project aims to make a significant contribution to the management of the COVID-19 crisis. In sepsis, also known as blood poisoning, a dysregulated host response of the body to an infection leads to life-threatening organ failure; this is also the case in severe cases of the disease ""Coronavirus Disease-2019 (COVID-19)"" caused by the virus SARS-CoV-2. These particularly severe courses with high mortality are characterized in most cases by the development of a pronounced systemic, self-perpetuating inflammatory response. Tumor necrosis factor a (TNF-a) is a signaling molecule of the immune system, a so-called cytokine, which is involved in local and systemic inflammatory reactions and regulates the activity of various immune cells. TNF-a is regularly elevated in severe courses of COVID-19. The overall objective of this project is to evaluate the safety and efficacy of the anti-TNF-a antibody infliximab compared to standard therapy in the treatment of patients with severe COVID-19 disease. It is planned to conduct a so-called randomized, controlled, multicenter, open-label Phase 2 study. COVID-19 patients who are hospitalized and have a defined severe systemic inflammatory response and impaired lung function will be treated with infliximab, a drug already established and approved for other disease entities, by expanding the indication. We hope that by neutralizing TNF-a with infliximab, the strong inflammatory reaction that occurs will be slowed down, the severity of the disease course will be mitigated, and thus the development of sepsis will be prevented. The results of this study could directly influence the therapy of patients with COVID-19 worldwide, as the drug used is already available internationally.",2021,2023,Jena University Hospital,906440.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2021 +C07791,03COV11A,CORONA - UVDecon - Joint project - UV LED for decontamination in detection systems; subproject 1: UV LED for decontamination in automated detection systems,The goal of the project is to rapidly refine an instrument platform to address market feedback on real-time PCR thermocyclers used during the pandemic period and changing acute detection requirements.,2020,2023,Analytik Jena AG,893416.17,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07792,03COV11B,CORONA - UVDecon - Joint project - UV LED for decontamination in detection systems; subproject 2: Universal UV LED module for system integration,"In this project, led by Analytik Jena, an instrument system is to be further developed which will be used for the simultaneous identification of SARS-CoV-2 by real-time PCR and the performance of antibody tests using existing detection kits in an adaptable purification unit. In the subproject UV-LED modules will be developed for sample room decontamination.",2020,2022,Forschungsverbund Berlin e.V.,82554.47,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07793,03COV12,"CORONA - FUNKFFP2 - Development of a functionalized, regenerable FFP2 mouth-nose mask with high wearing comfort","The main objective of the R&D project is to develop a novel, functionalized, easily disinfectable or sterilizable oral-nasal mask with antibacterial and antiviral functional structures that can be sterilized by simple superheated steam treatment at T=120-140 °C in a relatively short time, while essentially retaining its filtration effect. This includes: an increase in filtration effectiveness for the liquid aerosol components and ultra-fine particles, the highest possible air permeability (low breathing resistance), the mask-internal disinfection of the liquid droplets and particles fixed by the nonwoven material, the reusability of the mask by washing and disinfection after use, and environmentally sound disposal after the period of use has expired.",2020,2022,Norafin Industries (Germany) GmbH,260267.14,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C07794,03COV14,CORONA - CorTEX - Identification and definition of fields of action for the substitution of petrochemical materials in textile medical disposables with reference to the current Corona pandemic.,"The Corona pandemic posed an unprecedented challenge to the nation's medical supply infrastructures. Particularly in the area of textile medical disposables (tmE), there were sometimes unforeseeable supply bottlenecks with urgently needed medical material. Especially in this application field, there are strong dependencies on outsourced value chains and raw material supply process chains, which can lead to critical bottlenecks in the sometimes sensitive medical infrastructure. The CorTEX project therefore aims to identify and analyze substitution potentials, taking into account regionally available materials and processing capacities, regionally available know-how, and ecologically questionable petrochemical raw materials in tmE. Preferred fields of action are to be delineated in which material substitution leads to significant improvements in product-specific life cycle assessments and to the stabilization of supply chains in the event of a pandemic. The latter can potentially be achieved through the regionalization of value chains (predominantly national value creation through complementary integration of international partners). The identification of basic technical requirements, competencies and know-how of regional actors as well as the analysis of the current supply infrastructure with tmE are the first priority. The analysis of concrete fields of application for the identification of the greatest possible ecological potentials as well as investigations for the practical validation of the feasibility of potential-rich raw material/material substitutions will take place in a second step.",2020,2021,Sachsen-Leinen e.V.,145930.94,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Secondary impacts of disease, response & control measures | Health Systems Research","Other secondary impacts | Medicines, vaccines & other technologies",2020 +C07795,03COV16A,CORONA - COVMon - Monitoring concepts for SARS-CoV-2 - epidemiology and co-infections; subproject 1,"A detailed understanding of the epidemiology of COVID-19 is of central importance for an efficient control of the outbreak. After the phase of general shut-down, efficient monitoring strategies as well as the clarification of open questions regarding the spread of SARS-CoV-2 and the causes of mortality in hospitalized COVID-19 patients are of highest relevance. In particular, they complement the activities of the national research network and seroprevalence studies underway at numerous sites in Germany. Within the framework of an interdisciplinary project study on the epidemiological characterization of COVID-19, questions will be addressed that specifically require an interdisciplinary approach and that are not or insufficiently addressed in current, Germany-wide research projects on epidemiology and diagnostics. Against this background, COVMon will address the following questions in particular: 1. which monitoring concepts are suitable for early detection of virus spread in childcare facilities? 2. which co-infections occur in patients with severe COVID-19 infection? 3. What is the role of animals in the transmission of SARS-CoV-2? Answering these questions will make a critical contribution to our understanding of the epidemiology of the SARS-CoV-2 pandemic in Germany and thus provide a rational basis for decisions on containment measures.",2020,2022,Julius-Maximilians-Universität Würzburg,830306.3,Animals | Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Clinical characterisation and management",Diagnostics | Animal source and routes of transmission | Disease surveillance & mapping | Prognostic factors for disease severity,2020 +C07796,03COV16B,CORONA - COVMon - Monitoring concepts for SARS-CoV-2 - epidemiology and co-infections; subproject 2,"A detailed understanding of the epidemiology of COVID-19 is of central importance for an efficient control of the outbreak. After the phase of general shut-down, efficient monitoring strategies as well as the clarification of open questions regarding the spread of SARS-CoV-2 and the causes of mortality in hospitalized COVID-19 patients are of highest relevance. In particular, they complement the activities of the national research network and seroprevalence studies underway at numerous sites in Germany. Within the framework of an interdisciplinary project study on the epidemiological characterization of COVID-19, questions will be addressed that specifically require an interdisciplinary approach and that are not or insufficiently addressed in current, Germany-wide research projects on epidemiology and diagnostics. Against this background, COVMon will address the following questions in particular: 1. which monitoring concepts are suitable for early detection of virus spread in childcare facilities? 2. which co-infections occur in patients with severe COVID-19 infection? 3. What is the role of animals in the transmission of SARS-CoV-2? Answering these questions will make a critical contribution to our understanding of the epidemiology of the SARS-CoV-2 pandemic in Germany and thus provide a rational basis for decisions on containment measures.",2020,2022,Universitätsklinikum Würzburg,830306.3,Animals | Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Animal source and routes of transmission,2020 +C07797,03COV16C,CORONA - COVMon - Monitoring concepts for SARS-CoV-2 - epidemiology and co-infections; subproject 3,"COVID-19 Patients in intensive care units (ITS) often need mechanical ventilation or even receive extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA) procedures. These applications, together with the other invasive device applications on ITS (urinary tract catheters, vascular catheters) could lead to a high risk for nosocomial infections, but also multidrug-resistant pathogens (MRE) during the stay on the ITS. Currently, however, there is no system to record such NI and MRE systematically and in a uniform structure on a larger number of ITS in COVID-19 patients. In COVMon-TV3, a surveillance system for NI/MRE in COVID-19 ITS patients will be developed and applied. The data obtained will be used to calculate epidemiological characteristics. These data will be made available to the participating ITS in a suitable form together with reference data (feedback) and can thus be used for internal quality management. In addition, an analysis of the NI and MRE data in comparison to other ITS patients is to be carried out in order to be able to describe and present the risk for NI and MRE of COVID-19 patients to non-COVID-19 patients on ITS.",2020,2022,Charité - Universitätsmedizin Berlin,637851.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,Data Management and Data Sharing,,,Germany,Germany,"Secondary impacts of disease, response & control measures | Epidemiological studies",Indirect health impacts | Disease susceptibility,2020 +C07798,03COV16D,CORONA - COVMon - Monitoring concepts for SARS-CoV-2 - epidemiology and co-infections; subproject 4,Systematically collect and evaluate data on SARS-CoV-2 infections in animals and assess the importance of animals in outbreak and maintenance of the epidemic in humans in the context of the One Health approach.,2020,2022,Friedrich-Loeffler-Institut Bundesforschungsinstitut für Tiergesundheit,291915,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Epidemiological studies,Disease transmission dynamics,2020 +C07799,03COV17A,CORONA - ViKon - Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity Visrus binding conjugates; subproject 1: ViKon HKI.,"In this subproject, basic principles will be established and input materials provided to enable selective addressing of the SARS-CoV-2 pathogen and its effective, therapeutically efficient elimination by endogenous processes. A variant of the ACE2 receptor domain that is competitive with the native sequence will be identified (WP1), a bioorthogonal linkage method will be established (WP3), biophysical assays for at least four surface peptides will be performed (WP4), and exposure data for at least one frontrunner nanoparticle drug will be generated in a rodent model (WP5).",2021,2023,Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.V. Hans-Knöll-Institut,1322159.72,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C07800,03COV17B,CORONA - ViKon - Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity Visrus binding conjugates; subproject 2: Polymer-based nanoparticles and microparticles with antiviral binding motifs.,"In this subproject, the chemical and polymer chemical work as well as the formulation of the polymers for the production of the virus-binding particles will be carried out. The aim is to prepare polymers with reactive end groups to which short ACE2 receptor peptides (produced in AS1) are coupled. By varying the coupling chemistry and the conditions for formulating the polymer-peptide conjugates into nanoparticles and microparticles, optimized particles for binding SARS-CoV-2 viruses will be obtained. The subproject is thus integrated into the main focus 2 (AS2) of the joint project. However, in close collaboration with the cooperation partners, supporting work will also be carried out in AS3 and AS5.",2021,2023,Friedrich-Schiller-Universität Jena,449318.2,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C07801,03COV17C,"CORONA - ViKon - Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity Visrus binding conjugates; subproject 3: Functional testing of binding, neutralization and phagocytosis induction of SARS-CoV2-binding microparticles.","The interaction of the surface protein (spike protein) of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) of human cells mediates the uptake of virus particles into the cell interior and thus forms the starting point of infection. Due to its small size, elimination of SARS-CoV-2 by phagocytosis is not normally possible. However, phagocytosis can be exploited to eliminate viruses. This requires that viruses are bound to sufficiently large aggregates (> 400 nm) that can be recognized and rendered harmless by immune effector cells such as macrophages. In this project, ACE2 receptor peptide analogs will be tailored to couple to microparticles to provide a therapeutically effective competitor to surface fixation of viruses to human cells. By coupling the host cell receptor domain to microparticles, on the one hand, the uptake of SARS-CoV-2 into the host cell should be competitively prevented and, on the other hand, the targeted destruction of these aggregates by phagocytosis should be promoted. In this subproject, the ACE2-functionalized nanoparticles will be characterized with respect to their interaction with viral particles and macrophages. Experimental systems will be established to investigate the essential steps of the proposed mechanism of action: 1) the binding of the particles to the viral spike protein, 2) the ability to stop infection by direct interaction between viral particles and the cellular ACE2 uptake receptor (""neutralization""), and 3) the ability to induce their phagocytosis and elimination by cells of the immune system after binding of viruses. The aim is to perform a range of functional assays within a broadly available safety level (S2) by using so-called pseudoviruses, allowing optimization of peptide-loaded particles in terms of binding affinity and phagocytosis induction.",2021,2023,Julius-Maximilians-Universität Würzburg,558612.73,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C07802,03COV17D,CORONA - ViKon - Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity Visrus binding conjugates; subproject 4: Microparticle-mediated inhibition of SARS-CoV-2 replication in vitro.,"The subproject applied for here is part of the joint project ""Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity virus-binding conjugates"". In this subproject, libraries of virus-binding conjugates (VBK) will be investigated in vitro for their potential to inhibit cell entry and thus replication of SARS-CoV-2. These analyses require biological protection level 3 (BSL-3 laboratory), which is given at the Heinrich Pette Institute (HPI). In the present subproject, mainly a human lung cell line (Calu-3) will be used, which has been identified in preliminary studies as a very good in vitro model for SARS-CoV-2 infections. The planned inhibition assays will be optimized stepwise in a time- and dose-dependent manner to achieve an optimal inhibition of viral replication. Subsequently, the best candidates will be further validated and characterized in primary human lung cells. All necessary techniques to achieve these goals will be routinely performed in Prof. Gabriel's group at HPI. Thus, the final goal of this subproject is the identification, validation and characterization of one or more VBCs with maximal inhibition of SARS-CoV-2 in vitro.",2021,2023,"Heinrich-Pette-Institut, Leibniz-Institut für Experimentelle Virologie",414169.81,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C07803,03COV18A,CORONA - Parmenides - RapidCorona - TP 1,"The Corona pandemic shows how helpful broad-based screening processes could be. A rapid indicator ""pre-sorts"" huge populations, and medical diagnosis is then made in enriched populations. Therefore, a rapid-informing, low-cost, ubiquitous clue to detect corona viruses in the form of a chewing gum should be developed. These are to be equipped with a ""read-out"" that everyone understands - a bitter taste in case of infection. The working hypothesis is that infection with corona viruses causes certain enzymes in saliva to appear or be upregulated, and that this makes it possible to distinguish sick people from healthy people even in asymptomatic stages. This enzyme in saliva, which indicates the corona virus, is the target enzyme. The sensors to be developed - these are processed in the chewing gum - are cut only by the target enzyme (i.e. only in Corona sufferers) and only after this cut do they produce a bitter taste. Then the chain closes (i) Corona viruses in the throat → (ii) target enzyme increased in saliva → (iii) chewing gum → (iv) taste → (v) person is warned.",2021,2022,Julius-Maximilians-Universität Würzburg,467326.08,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C07804,03COV18B,CORONA - Parmenides - RapidCorona - TP 2,"The Corona pandemic shows how helpful broad-based screening processes could be. A rapid indicator ""pre-sorts"" huge populations, and medical diagnosis is then made in enriched populations. Therefore, a rapid-informing, low-cost, ubiquitous clue to detect corona viruses in the form of a chewing gum should be developed. These are to be equipped with a ""read-out"" that everyone understands - a bitter taste in case of infection. The working hypothesis is that infection with corona viruses causes certain enzymes in saliva to appear or be upregulated, and that this makes it possible to distinguish sick people from healthy people even in asymptomatic stages. This enzyme in saliva, which indicates the corona virus, is the target enzyme. The sensors to be developed - these are processed in the chewing gum - are cut only by the target enzyme (i.e. only in Corona sufferers) and only after this cut do they produce a bitter taste. Then the chain closes (i) Corona viruses in the throat → (ii) target enzyme increased in saliva → (iii) chewing gum → (iv) taste → (v) person is warned.",2021,2022,Universitätsklinikum Würzburg,467326.08,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C07805,03COV19A,CORONA - VirAn- Joint project: High-throughput multiplex bead assays; subproject 1: Multiplex beads for life science research and diagnostics and suspension bead assays for life sciences,"The overall objective of the subproject is to synthesize, research and develop new multiplex beads to be used as basic and consumable materials in research to address the Covid-19 pandemic: a) Beads to be used in suspension bead assays b) Beads to be used in solid phase assays. In addition, new modular multiplex suspension bead assays will be developed and explored for use in research to address the Covid-19 pandemic. The subproject will explore the synthesis of microparticles via precipitation and emulsion polymerization, irreversible embedding of dyes into a polymeric bead matrix, targeted surface functionalization of dye-encoded microparticles, immobilization of biomolecules, especially antibodies onto the functional beads, and preparation, characterization of multiplex bead assays.",2020,2023,PolyAn Gesellschaft zur Herstellung von Polymeren für spezielle Anwendungen und Analytik mbH,513651.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07806,03COV19B,CORONA - VirAn- Joint project: High-throughput multiplex bead assays; subproject 2: Novel solid-phase bead assays for multiplex measurement of antibodies and inflammatory mediators in the diagnosis of virus-related respiratory diseases.,"The subproject focuses on a new solid-phase bead assay (SBA) for multiplex determination and characterization of antibodies as well as for single-molecule detection of biomarkers (antigens) in the context of diagnostics of respiratory diseases. The envisaged overall system can also be used for research into the efficacy of vaccines in vaccine development. In the subproject, a diagnostic overall system is developed, which consists of the subsystems SBA, measuring device and software. By applying this system to the determination of antiviral antibodies of different antibody classes and their avidity or the concentration of inflammatory mediators in blood sera, statements on the course of the disease and the immunocompetence of the patients or the effectiveness of vaccines should become possible. The main scientific and technical objectives are: 1. development of SBA for the determination of IgA, IgG, IgM antibodies against SARS-CoV-2 and influenza viruses and comparison with suspension bead assays, 2. development of a method for multiplex avidity determination of antiviral antibodies in blood sera, 3. development of an antigen SBA and a digital antigen SBA for the detection of the inflammatory mediators CRP and IL-6 as early markers of viral sepsis and comparison of both detection methods. Comparison with suspension bead assays, 4. development of a measurement device platform including control/evaluation software based on imaging fluorescence spectroscopy for the evaluation of digital bead assays, 5. development of an instrument system and SBA to perform avidity determinations of antibodies in blood sera and integration into the measurement device platform, 6. the performance of the new assays should reach and partly exceed that of the assays currently available on the market.",2020,2023,Attomol GmbH Molekulare Diagnostika,501982.15,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C07807,03COV19C,CORONA - VirAn- Joint project: High-throughput multiplex bead assays; subproject 3: Validation of multiplex bead assays.,"The aim of the overall project is to establish modular bead-based assays for the study of viral infections. In this context, the aim of the subproject is to validate the developed bead assays for the analysis of murine and human samples after infection with SARS-CoV-2 or influenza. Furthermore, after adaptation and further development of the bead assays, it will be evaluated to what extent the assays can contribute to the identification of early predictors for the course of the disease as well as to the monitoring of a possible therapy. Samples from risk groups (mouse models) will also be used for this purpose. With the help of these experimental approaches, the subproject described here should make an essential contribution not only to validating the assays, but also to improving them. In addition, the results obtained should contribute to a better understanding, diagnosis and early treatment of infections with SARS-CoV-2 and the corresponding course of the disease.",2020,2023,Helmholtz-Zentrum für Infektionsforschung GmbH,288117.49,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +C07808,03COV19D,CORONA - VirAn- Joint project: High-throughput multiplex bead assays; subproject 4: Validation and data analysis.,"With the VirAn kit, which is currently being developed by the VirAn team, customized multiplex assays can be rapidly assembled for the simultaneous - determination of IgG, IgM, IgA antibodies in serum, plasma or saliva against various respiratory viruses and - estimation of the immune status by measuring cytokine levels. Multiplex beads are used for this purpose, which can be read on flow cytometers or imaging systems commonly used in the laboratory. The determination of several parameters by means of one and the same measurement platform is a must if a quantitative comparison between the values is desired and if complex markers are to be identified. Furthermore, such multiplex measurement is a prerequisite when speed and affordability are important. The multiplex beads are easily scalable and the composition of the assay can be adapted to the respective requirements, as in a construction kit (custom-tailored assay). Within the scope of the subproject, the assay will be tested on human biological samples. In addition, user cases will be defined, data analysis tools will be set up and data analyses will be performed to identify multi-parameter predictive and diagnostic markers and immune correlates as well as to assess risks of complications.",2020,2023,Charité - Universitätsmedizin Berlin,382767.86,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C07809,03COV22A,CORONA - Travel-Dx - Quick test for mobility; subproject 2: Cor(e)LAMP,"The Corona Lockdown has shown in all clarity: Mobility is an extremely important factor in all our lives: TRAVEL-Dx-Cor(e)LAMP aims at accelerated on-site diagnostics to enable mobility in times of epidemic or pandemic. It involves the detection of SARS-CoV-2 using a LAMP-based procedure that can be performed on-site in a very short time. This is a major step towards acceleration and increased testing capacity, which leads to more mobility. Scientifically, the test detects Sars-CoV-2 specific gene segments and uses similar regions of the viral genome as the gold standard RT-PCR. However, because it does not use thermal cycling, the test is faster and easier to automate and can be reduced to as little as 15 min in favorable cases. A simple color change provides a binary YES/NO statement, which greatly facilitates handling and analysis in the field.",2020,2022,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,290443.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07810,03COV22B,CORONA - Travel-Dx - Quick test for mobility; subproject 2: Detection,"The detection of SARS-Cov-2 without the need for equipment has the advantage of being able to realize a rapid on-site detection. For this purpose, LAMP products must be made visible; this is usually done by means of fluorescence and is thus linked to a readout device. The aim of this subproject is to make a readout device dispensable and to offer an immediately visible detection by means of a lateral flow assay (test strip). The task is to develop stable molecular mechanisms that act like a switch and generate an unambiguous (color) signal triggered by a positive binding process, in this case viral RNA. The scientific goal is to increase the sensitivity sufficiently without loss of specificity. The concrete goal of this project is to identify the amplification products of a LAMP reaction unambiguously in a short time, while the detection reaction itself should be completed in a few minutes.",2020,2022,Universität Potsdam,299087.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07811,03COV24A,CORONA - Parmenides - DIRECT-Dx - TP1,"Within the framework of the joint project ""DIRECT-Dx"", antibodies directed against the SARS-CoV-2 virus are to be developed, which will serve as the basis for a new rapid test procedure. Compared to other diagnostics, such antibody-based direct detections indicate the intact and therefore infectious virus. With the aid of this test procedure, the alliance hopes to create an effective means of rapidly detecting any infections and thus isolating sources of infection at an early stage. A simple detection system, e.g. in the form of a color change or a strip test, is to be developed. In addition to simple handling, such an antibody-based detection method also offers the possibility of obtaining timely on-site results.",2020,2022,Universität Potsdam,834998.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07812,03COV24B,CORONA - Parmenides - DIRECT-Dx - TP2,"Within the framework of the joint project ""DIRECT-Dx"", antibodies directed against the SARS-CoV-2 virus are to be developed, which will serve as the basis for a new rapid test procedure. Compared to other diagnostics, such antibody-based direct detections indicate the intact and therefore infectious virus. With the aid of this test procedure, the alliance hopes to create an effective means of rapidly detecting any infections and thus isolating sources of infection at an early stage. A simple detection system, e.g. in the form of a color change or a strip test, is to be developed. In addition to simple handling, such an antibody-based detection method also offers the possibility of obtaining timely on-site results.",2020,2022,preclinics Gesellschaft für Präklinische Forschung mbH,834998.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C07910,NIHR132254,Procalcitonin: Evaluation of Antibiotic use in COVID-19 Hospitalised patients. (PEACH),,2020,2022,University of Leeds,951416.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",,2020 +C07911,NIHR133206,"New models of remote delivery, in drug and alcohol services, introduced during Covid-19",,2020,2022,University of Hertfordshire,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C07912,NIHR132243,"Supported remote rehabilitation post Covid-19: development, deployment and evaluation of a digitally-enabled rehabilitation programme",,2020,2022,University College London,1016553.89,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Clinical characterisation and management,Post acute and long term health consequences,2020 +C07913,NIHR132103,The prevention and treatment of persisting olfactory dysfunction following COVID-19 infection; a suite of Cochrane living systematic reviews,"This project proposes a suite of Cochrane systematic reviews on the prevention and treatment of olfactory dysfunction due to COVID-19. It is addressed to the Evidence Synthesis Programme. Olfactory dysfunction is a cardinal symptom of COVID-19 infection. This usually takes the form of partial or complete loss of olfactory function (hyposmia and anosmia respectively). For a significant proportion of patients this is only a transient phenomenon, and they recover a normal sense of smell relatively quickly. For others the problem can persist. It is a debilitating condition with a major impact on quality of life. The primary aims and objectives are: 1. To identify those interventions that have been used, or proposed, to prevent or treat olfactory dysfunction due to COVID-19 infection. 2. Working with patients and other stakeholders to identify a set of prioritised outcomes for use in systematic reviews evaluating the effectiveness of those treatments. 3. To publish - rapidly - a suite of Cochrane systematic reviews evaluating the effectiveness of these treatments, and any adverse effects, using the prioritised outcomes. 4. Anticipating limited data at this stage of the pandemic, to maintain these reviews as 'living' systematic reviews for a period of at least 24 months. 5. To inform practice (if effective treatments are identified) and research (if further trials are necessary). This work will be undertaken by an experienced team at Cochrane ENT using standard Cochrane methods. The identification of interventions and outcomes, and in particular the critical engagement with patients to do the latter, builds on experience of the Group in doing this in a number of other clinical areas. The Group will also use its experience of doing formal and informal 'living' systematic reviews. The key output is a suite of living Cochrane systematic reviews updated regularly over the next two years (the suite will comprise at least two reviews, as trials evaluating two interventions have already been identified). Secondary outputs include a prioritised list of patient-focused outcomes for systematic reviews of trials in patients with olfactory dysfunction.",2020,2022,University of Oxford,45235.51,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Adverse events associated with therapeutic administration",2020 +C07914,NIHR133168,"Remote-by-Default Care in the COVID-19 Pandemic: addressing the micro-, meso-, and macro-level challenges of a radical new service model","AIM In the context of COVID-19, to address micro- (technical tools, clinical techniques), meso- (organisational change) and macro (national infrastructure) aspects of a remote-by-default service model in primary care. OBJECTIVES 1. Validate and embed evidence-based tools for remote assessment and monitoring. 2. Support local implementation teams to overcome technical, operational and professional barriers and implement remote-by-default service models rapidly and at scale. 3. Generate and apply insights on how NHS infrastructure can better support and be supported by digital innovation in a time of crisis. RESEARCH QUESTIONS 1. How can technology support assessment and monitoring of patients at a distance? 2. How can we achieve rapid spread and scale up of remote-by-default models of primary care? 3. What insights can we glean from this time of crisis that will help build a more resilient NHS? OUTLINE METHODS 1. TOOLS: Qualitative research to develop instruments followed by quantitative validation studies. 2. IMPLEMENTATION AND SCALE-UP: Four contrasting case studies in different localities, nested in an over-arching analysis of national policy. Action research (informed by interviews, ethnography, documents, datasets) by virtual researchers-in-residence. 3. WORKSHOPS AND SCENARIO-TESTING: Involving policymakers, regulators, professional bodies, industry, patients/citizens, to identify ways to strengthen infrastructure for rapid change.",2020,2021,University of Oxford,475923.38,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C07915,NIHR130914,"A randomised controlled trial and feasibility study of the effects of an e-health intervention 'iSupport' for reducing distress of dementia carers, especially in the ongoing pandemic of COVID-19.","Background: Most of the 850,000 people living with dementia in the UK are cared for at home. Caregiving is known to have a detrimental effect on physical and mental health. Covid-19 has meant that many older people have to self-isolate, placing increasing pressures on carers. NICE recommend informal carers of people living with dementia should be offered training and psychoeducation to help them develop care skills and manage their own physical and mental health. Research question: Is carer distress significantly reduced in participants allocated to receive the iSupport e-health intervention compared to carers allocated to a control group? Objectives 1)To estimate the clinical and cost-effectiveness of the iSupport intervention, compared with brief advice 2)To undertake a process evaluation of the barriers and facilitators to the implementation of 'iSupport' at scale/ 3)To explore the feasibility of adapting iSupport for young carers Intervention: iSupport' is an internet-based psychoeducation skills development intervention. It consists of five themes and accompanying exercises; (i) introduction to dementia; (ii) being a carer; (iii) caring for me; (iv) providing everyday care; and (v) dealing with behaviour changes. Each session takes approximately 5-15 minutes. Carers can construct their own personalised plan and access which sessions they feel are most relevant to them at that point in time. Design: Individually randomised two-arm controlled trial with health economic evaluation and nested process evaluation. A separate non-randomised feasibility study of adapting the intervention for young carers. The research will take place with carers living in the UK. The study will start 1.01.2021 and run for 36 months. The RCT will recruit 356 informal carers (aged 18+) of a person with dementia, caring at least weekly at home for at least 6 months. The carers must self-identify as experiencing at least some stress, anxiety or depression. Participants assigned to the comparison group will receive information about dementia developed by the Alzheimer's Society. The feasibility study will involve 30 carers aged 11-17. The primary outcome will be reduction in carers' distress, as measured by the Zarit Interview (ZBI). Secondary outcomes assess reductions in depression (CESD-10), anxiety (GAD-7) improvements in resilience (RS-14), sense of competence (SSCQ), quality of the carer-patient relationship (QCPR), increases in dementia knowledge (DKAS) and the EQ-5D-5L. Impact: This will be the first study in the UK and the first in an English-speaking population of a globally targeted e-health intervention for dementia carers. iSupport may be especially important in the current climate of distancing and isolating, and benefit the mental health of dementia carers in the UK, who may feel better able to provide care. New knowledge regarding what may enhance or hinder the implementation of iSupport will be of benefit to our collaborators at the WHO by informing the international implementation of iSupport. In the long term, we envisage sustainability with 'iSupport' embedded and recommended as part of care packages in the UK. Given that there are 850,000 people diagnosed with dementia in the UK, and most of them live at home supported by a family member or friend, the number of carers that could benefit is substantial. This may lead to reductions in care home admissions and reductions in health and social care costs, benefiting the economy.",2020,2023,Bangor University,2003496.77,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C07916,NIHR133409,Exploratory economic modelling of severe acute respiratory syndrome coronavirus 2 viral detection point of care tests and serology tests: Testing within care homes.,,2020,2020,The University of Sheffield,166687.5,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C07917,NIHR133170,Exploratory economic modelling of severe acute respiratory syndrome coronavirus 2 viral detection point of care tests and serology tests: Testing at admission to hospital from Accident and Emergency departments,,2020,-99,The University of Sheffield,,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions, +C07918,unknown,Investigating SARS-CoV-2 Transmission in North London Communities,,2020,-99,London School of Hygiene & Tropical Medicine,163306,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C07962,7201101189,"Investigating Interaction Mechanism of Risk Perception, Coping Behavior and Emotional Evolution between Public in China and Korea under Major Public Health Emergencies",,2020,-99,"Renmin University of China, Pusan National University",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Natural Science Foundation of China (NSFC) | National Research Foundation of Korea (NRF),China | South Korea,Western Pacific,Western Pacific,Western Pacific,,,,China | South Korea,China | South Korea,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C07963,8201101284,Development of bacterial vector-based COVID-19 vaccine,,2020,-99,"Nankai University, Korea University",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Natural Science Foundation of China (NSFC) | National Research Foundation of Korea (NRF),China | South Korea,Western Pacific,Western Pacific,Western Pacific,,,,China | South Korea,China | South Korea,"Vaccines research, development and implementation",Pre-clinical studies, +C07964,7201101190,Modeling and Analyzing a Contact Social Graph for Predicting and Managing Outbreak Disease,,2020,-99,"Zhejiang University, Sungkyunkwan University",,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Natural Science Foundation of China (NSFC) | National Research Foundation of Korea (NRF),China | South Korea,Western Pacific,Western Pacific,Western Pacific,,,,China | South Korea,China | South Korea,Epidemiological studies,Disease surveillance & mapping, +C07971,2020-06320,Design and development of mucosal vaccine vectors in commensal bacteria expressing SARS-CoV-2 antigens - a potential prophylactic method,"Medical biotechnology (specializing in cell biology (incl. Stem cell biology), molecular biology, microbiology, biochemistry or biopharmacy)",2020,-99,Karolinska Institutet,180000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Research Foundation of Korea (NRF) | Swedish Research Council,South Korea | Sweden,Europe | Western Pacific,Europe,Europe,Innovation,,,Sweden,Sweden,"Vaccines research, development and implementation",Pre-clinical studies, +C07972,2020-06315,ARCTIC: contAct tRaCing prevenTion of Covid-19,"Public health science, global health, social medicine and epidemiology, Signal processing, Systems science, information systems and informatics",2020,-99,KTH Royal Institute of Technology,180000,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Research Foundation of Korea (NRF) | Swedish Research Council,South Korea | Sweden,Europe | Western Pacific,Europe,Europe,,,,Sweden,Sweden,,, +C07973,2020-06311,Focus on SARS-CoV-2 RNA Modification as a New Therapeutic Approach,"Microbiology, Cell and Molecular Biology",2020,-99,University of Gothenburg,180000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Research Foundation of Korea (NRF) | Swedish Research Council,South Korea | Sweden,Europe | Western Pacific,Europe,Europe,,,,Sweden,Sweden,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C07974,2020-06312,Identification of immunological host factors that regulate SARS-CoV-2 infection,"Cell and molecular biology, Microbiology in the medical field, Immunology in the medical field",2020,-99,Karolinska Institutet,180000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Research Foundation of Korea (NRF) | Swedish Research Council,South Korea | Sweden,Europe | Western Pacific,Europe,Europe,,,,Sweden,Sweden,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C08219,SE0557,SARS-CoV-2 zoonotic/reverse zoonoses animal model,"Coronavirus disease 2019 (COVID-19) is an infectious viral zoonotic disease caused by beta-coronavirus SARS-CoV-2, ACDP3/SAPO unclassified agent requiring bio-containment level (BCL) 3 when virus amplification and bio-aerosols are employed. Coronavirus pathogens are capable of causing human illness ranging from common colds to severe diseases, including Middle East Respiratory Syndrome (MERS-CoV), and Severe Acute Respiratory Syndrome (SARS-CoV) (Cui et al., 2019). COVID-19, was declared a global pandemic by WHO on 11 March 2020. Coronaviruses are known to infect humans, birds and mammals with transmission through fomites, airborne or faecal-oral routes. Epithelial cells in the respiratory and gastrointestinal tract are the primary target cells, with an estimated incubation period ranging from 2-14 days, or longer. Shedding of virus can be very variable from one to several weeks (49 days in a human longest currently recorded). The predominant route of transmission of COVID-19 is via aerosol transmission or contact of contaminated items with mucous membranes. The current spread of COVID-19 is a result of human-to-human transmission (ECDC Report). To date, there is no evidence that companion animals play an important role in COVID-19 epidemiology. There have been reports of infections detected in dogs, cats and tigers that have had direct or indirect contact with positive human cases, indicating cases of reverse zoonoses, which were sub-clinical or mild in nature (Shi et al., 2020; OIE Advisory Group). Public Health and Veterinary Services are using a One Health approach to share information and conduct risk assessments for a person with COVID-19 reporting contact with companion or other animals (key species; dogs, cats (including large felids), ferrets, primates or pigs). The ferret has proven to be a good model for mild-moderate human and animal disease as a result of infection with SARS-CoV-2 viruses based on modest clinical presentation at 1-2 weeks post exposure, viral shedding from the upper (nose and throat) and lower (lungs) respiratory tracts over 1-3 weeks, and gastrointestinal tract (rectal) over a shorter period (Kim et al., 2020; Richard et al., 2020; Shi et al., 2020). The major objective of this proposal is to adapt the APHA ferret-influenza A virus model (animal/human), incorporating the PHE-Porton ferret-SARS-CoV-2 model (human), and establish full COVID19 research and diagnostic capability at APHA-Weybridge using the BCL3 animal and laboratory facilities. This first phase is a challenge/clinical sample/reagent pilot study to build capability and extend the in vitro tool box (molecular/histochemistry) projects undertaken in March 2020. This work will allow more advanced study designs (including assessment of vaccines and therapeutics) to be undertaken in the near future. The design of the in vivo pilot will incorporate infection of ferrets with a suitable virus dose to confirm clinical observations, virus shedding profiles, viral load in organs and immune responses. In addition, environmental samples will be collected to determine if virus can be detected on animal fur, in feed and water and on hard surfaces (e.g. metal/plastic). Reagents that will be made available for future funded work include carnivore-adapted virus, positive control antibodies for serological test development as well as positive control tissues for virology, histopathology and immunology studies with relevance to animal and human investigations. This information and capability will be taken forward as evidence of APHA-Weybridge's competence in this critical new and emerging zoonotic disease research area with UK and European partners providing further added value for Defra. Our large ferret capacity is greater than any other location in the UK and most facilities across the world and allows us to undertake complex multi-armed designs for disease interventions and/or duration of study.Objective 1.0 Establish the ferret/SARS-CoV-2 model at APHA-Weybridge 30/04/20 Skill development (e.g., training to enable novel skill acquisition and capability; development of existing/novel skills base) 2.0 Create positive control reagents - virus, infected tissues and polyclonal antibodies 15/05/2020 Disease threat and mitigation (e.g., pathogen characterization; diagnostic development; optimization and validation of tests) 3.0 Characterise host and virus pathogenesis parameters 29/05/2020 Knowledge acquisition (e.g., pathogenesis; epidemiology; transmission; host competence etc) 4.0 Assess contamination of environmental samples - animal fur, feed and surfaces 29/05/2020 Environmental and safety (e.g., inactivation work, sampling techniques, pathogen matrix evaluation) Impacts: Establishing the ferret model of COVID19 will allow APHA to play a part in disease prevention and control from both human and animal perspectives. Assessment of developmental vaccines and therapeutic interventions, and assess host responses with respect to infection duration (waxing and waining of shedding), and re-infection possibilities and parameters, plus host age, sex and metabolic/underlying conditions. The implementation of COVID19 response (diagnostics and applied research) allows us to test our responsiveness to 'Disease-X' scenarios, adapting our skills sets to novel zoonotic disease challenges on behalf of Defra and the wider UK government. Provide public reassurance that .Gov.UK science is responsive and productive.",2020,2020,APHA (Animal and Plant Health Agency),30042,Animals | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Research on Capacity Strengthening","Diagnostics | Pathogen morphology, shedding & natural history | Disease models | Animal source and routes of transmission | Institutional level capacity strengthening",2020 +C08227,unknown,Accelerating Changes in Norms about Social Distancing to Combat COVID-19 in Mozambique,"Social distancing is one of the most important health behaviors limiting the spread of COVID‐19, but people may practice it insufficiently for multiple reasons: they may not believe or realize that community norms have shifted towards support for social distancing, and they may not realize its public health benefits. This project is supporting Mozambique's effort to promote social distancing, in collaboration with the government's health research center for the central region. In a representative sample of 3,000 households across three provinces, many of whom were displaced by Cyclone Idai, researchers are evaluating two different messaging approaches to promote social distancing. One emphasizes that others in the community-either prominent individuals or a high share of other households-support social distancing. The other emphasizes social distancing's public health benefits. Data from high-frequency phone-based surveys will inform the government about how COVID-19-related knowledge, beliefs, and preventative behaviors are changing over time.",2020,2020,"Beira Operational Research Center at the Ministry of Health, Mozambique",,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Africa,Africa,,,,Mozambique,Mozambique,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C08228,unknown,Cash and Compliance with Social Distancing: Experimental Evidence from Ghana,"As coronavirus begins to spread in developing countries, an important question is whether poor households will adhere to social distancing given the likely inability to work remotely, and the subsequent large income losses. In such a context, mobile money transfers may not only help households maintain consumption levels, they may also complement social distancing policies - those that get the cash may work less, and stay at home more. We are launching a three-arm mobile money transfer study in Ghana to test this idea. Specifically, using a subset of relatively low-income households from the Ghana Panel Survey (a representative panel dataset collected over the last decade) we will randomly assign households to a treatment group that receives eight weekly transfers or a control group the receives only a single transfer. We will examine effects on a battery of economic and psychological measures of well-being as well as adherence with social distancing and self-isolation.",2020,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,,Africa,,,,,Ghana,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Economic impacts,2020 +C08229,unknown,Communication to Promote Healthy Behaviors in Urban Slums in Kenya During COVID-19,"Sub-Saharan Africa contains many densely overcrowded and poor urban slums at high risk of COVID-19 outbreaks. In these contexts, sanitation and social distancing measures are near impossible, and COVID-19's rapid spread is a devastating prospect. To control the pandemic's spread, the Kenyan Ministry of Health COVID-19 Taskforce has implemented initial prevention and mitigation measures. To inform the Taskforce strategy, this study will deploy rapid phone-based surveys every two weeks on knowledge, attitudes and practices to approximately 7,500 heads of household sampled from existing randomized evaluation cohorts across five urban slums in Nairobi. Baseline findings on awareness of COVID-19 symptoms, perceived risk, awareness of and ability to carry out preventive behaviors, misconceptions, and fears will inform Taskforce interventions. In subsequent rounds, behavior change messages will be randomly assigned to measure effectiveness, or if randomization is not feasible, survey questions on exposure and response to government campaigns will be evaluated using causal inference approaches.",2020,-99,"Ministry of Health, Kenya",,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Africa,Africa,,,,Kenya,Kenya,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +C08230,unknown,Effective Communication and Dissemination of Critical COVID-19 Information with Syrian Refugees in Turkey,"This study examines how to most effectively provide mitigation-related information on COVID-19 to Syrian refugees living in Turkey. Researchers are identifying small and medium-sized enterprise owners who can act as information ""seeds"" to the broader Syrian refugee community because they are more likely to have access to important resources, such as the internet. The study is testing how trust in the original information source (either a Syrian NGO or a Turkish NGO) and enterprise owners' autonomy in delivering the information impacts the breadth and depth of information dissemination and subsequent behavioral and health outcomes. Researchers will track sign-ups for an information service and engagement in information dissemination. High-frequency follow-up calls will capture health outcomes, information retention, and self-reported social and health behavior. The study will also track how COVID-19 impacts refugee-owned businesses.",2020,-99,Syrian Economic Forum,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Europe,Europe,,,,Turkey,Turkey,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C08231,unknown,Impact of Cash Assistance to Venezuelan Migrants on Resilience to the Negative Impacts of COVID-19,"Cash assistance is a major component of the humanitarian response to refugee and migration crises around the globe, but we have limited evidence on its impact on resilience and migration, especially in the current context of mobility restrictions due to a public health crisis. In partnership with Mercy Corps, the Immigration Policy Lab is using a novel technology-assisted, partially automated WhatsApp survey methodology to evaluate an ongoing cash assistance program for Venezuelan migrants in Colombia. Researchers will evaluate the impact of cash on household resilience and return migration in the face of a global pandemic. The regression discontinuity design is based on a vulnerability score which distinguishes households that will and will not receive monthly cash assistance and we will conduct follow up surveys at three, six, and nine month intervals.",2020,-99,"Immigration Policy Lab (IPL), Mercy Corps",,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Americas,Americas,,,,Colombia,Colombia,"Secondary impacts of disease, response & control measures",Social impacts, +C08232,unknown,State Engagement with Religious Leaders for Effective COVID-19 Crisis Response,"The goal of this study is to test whether outreach with religious leaders in Pakistan can enhance state effectiveness at dealing with the COVID-19 public health crisis. State interactions with religious leaders present both a challenge and an opportunity: there has been lack of clarity on the official stance on whether and how congregational prayer is restricted as part of ongoing lockdowns. Many mosques in Pakistan continue to hold congregational prayer, and there have been some clashes between the state and mosques over this issue. Effective outreach to the clergy at the community level may help to address this challenge. The research team will conduct information treatment calls with a randomized sub-sample of imams to test secular and religious approaches to persuading community imams to carry out social distancing within their mosques.",2020,2020,Center for Economic Research in Pakistan (CERP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Eastern Mediterranean,Eastern Mediterranean,,,,Pakistan,Pakistan,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C08233,unknown,Understanding Economic Outcomes and Resilience to COVID-19: Evidence from the Kenya Life Panel Survey,"COVID-19 is causing major health and economic challenges for low-income countries in sub-Saharan Africa. The Kenya Life Panel Survey (KLPS) is uniquely situated to address numerous key questions about the effects of the pandemic. The KLPS is a 20-year longitudinal survey on health, educational, nutritional, demographic, social, and labor market outcomes among a sample of thousands of Kenyans who were participants in one or more randomized health, skills training, and financial capital interventions during childhood and adolescence, and collects intergenerational data on their children. Researchers are adding a phone survey round to KLPS to track COVID-19 exposure, knowledge and coping mechanisms (including migration); measure downstream long-term effects of adolescent interventions on responses; and determine how crisis experiences affect subsequent outcomes for adults and children. Researchers are estimating effects using the original experiments, and spatial and temporal variation in survey timing and COVID-19 intensity and policies across Kenya.",2020,2020,National Institutes of Health (NIH),,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Africa,Africa,,,,Kenya,Kenya,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C08234,unknown,Vulnerability and Trust in the Aftermath of COVID-19 in Uganda,"COVID-19 has already disrupted community life and will surely alter community social dynamics for years to come. This project aims to identify and track over time citizens' compliance with COVID-19 mitigation policies and their access to relief services in Kampala, Uganda. Building on an existing study in which certain residents were randomly assigned to attend meetings with Kampala Capital City Authority (KCCA)-which is responsible for the city's health centers, public schools, and other public services-researchers will survey the study's representative sample of urban residents to understand patterns of rule compliance, uncover how the crisis alters patterns of intra-group and inter-group trust (using baseline information collected prior to the pandemic), and identify and track overtime populations that are vulnerable to disruptions caused by the pandemic. The ongoing randomized evaluation will also help researchers to understand how this compliance is shaped by contact with a key governmental institution. Embedding this COVID-19 survey into a data collection process that extends to 2021 will allow researchers to gain a long-term perspective on community resilience.",2020,-99,Kampala Capital City Authority (KCCA),,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO) | Innovations for Poverty Action",United Kingdom | International,Europe | International,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement, +C09329,221377/Z/20/Z,Funding of Covid-19 R&D Priorities in Africa,"Success against the Covid-19 pandemic requires a transdisciplinary approach incorporating social sciences and humanities, economic research and health systems research. It also requires access to funding. The African Academy of Sciences (AAS), through its hosted AESA Platform, acts as Secretariat for this Fund for Covid-19 R&D priorities in Africa. This Fund is seeking proposals against identified priorities; coordinating a network of researchers working on Covid-19 R&D to build a clinical research and trials platform for Africa; and taking a longer-term view to address pandemic preparedness in research actions.  The Fund is open to multiple priority areas for research and development, including:1. Epidemiological studiesStudies to define disease severity and susceptibility of particularly groups at high risk of severe infection; the role of different age groups in transmission; the impact of control and mitigation measures; and to predict the most effective interventions.2. Clinical managementStudies to define the natural history of Covid-19 infection including the identification of prognostic factors for severe disease and the identification of vulnerable groups; and studies to improve the clinical outcome of Covid-19, including strategies to improve the processes of care.3. Infection prevention and controlStudies to assess the effectiveness, in both healthcare and community settings, of movement control strategies in preventing secondary transmission and of personal protective equipment in reducing the risk of transmission.4. Candidate vaccines, diagnostics and therapeuticsClinical trials of potential treatments and preventative strategies, facilitated by the recent AESA programme launched as the Clinical Trials Community online platform.5. Ethical considerations for researchStudies on culturally appropriate approaches to the ethical, social and legal issues prevalent in emergency situations, such as presented by Covid-19.6. Social sciences in a pandemic responseEngagement to bring community voices to decision-making processes, to understand non-intended consequences of pandemic-control decisions and to understand contextual vulnerability; and studies to mitigate impacts of the socio-economic and political externalities of Covid-19.",2020,2022,African Academy of Sciences,712440.3,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Africa,,,,Kenya,Kenya,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience","Diagnostics | Pathogen morphology, shedding & natural history | Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures | Pre-clinical studies | Pre-clinical studies | Approaches to public health interventions | Community engagement",2020 +C09330,221750/Z/20/Z,PlanetDivoc91,"A 9-part digital comic for young adults (YA) aged 16-25 providing an alternative, character-based narrative about a pandemic. Co-created with young adults from across the globe, multidisciplinary researchers and experts, renowned comic writers and artists, PlanetDivoc91 offers audiences diverse perspectives on how to make sense of a pandemic. It connects and empowers YA - whose voices have been marginal in the COVID crisis - to be heard in current and future pandemic research and policy. This proposal builds on work already started in the UK and internationally, to extend in greater depth globally, particularly in India and South Africa (SA).",2020,2021,University of Manchester,194990.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C09331,221558/Z/20/Z,Full text COVID-19 preprints in Europe PMC,"In this pandemic, researchers have responded by publishing results rapidly, often through preprints. In fact, about half of the publications in Europe PMC on COVID-19 are preprints rather than peer-reviewed journal articles. Currently, the full text of these preprints are scattered as PDFs on preprint servers, or, available as a non-standard set of documents for machine learning purposes. This proposal is about making the full text of COVID-19 preprints available on Europe PMC, a large and sustainable life sciences archive, for reading and reuse via a standard XML format, alongside peer-reviewed full text articles. Being able to easily search and read preprint full text on a site already frequented by millions of users a month, means that they will be significantly more discoverable by people, and will be able to make use of existing infrastructure to integrate into the typical ecosystem of publications - for example, linking to related data - as well as being more open to scrutiny. This will accelerate scientific research on COVID-19, provide an opportunity to build new open and rapid publication systems, and form a corpus for future history of science research.",2020,2021,European Bioinformatics Institute,525673.2,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,,,2020 +C09332,221563/A/20/Z,Global Goal: Unite for Our Future,"Global Citizen and the European Commission ran a campaign, Global Goal: Unite for Our Future, with the aim of ensuring that everywhere in the world, those who need them have access to COVID-19 tests, treatments, and vaccines. The campaign also sought to lessen the impact of COVID-19 on the world's most vulnerable people, ensuring they still have access to education, clean water, and more. The campaign, launched under the patronage of European Commission President Ursula von der Leyen, focused on the development of tools to tackle COVID-19, and ensuring that these tools are available to all communities equally, as well as mitigating the impacts of COVID-19 on those living in poverty.",2020,2020,Global Poverty Project Inc,1040000,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Communication,2020 +C09333,221406/Z/20/Z,Highlight It: A Public Information Campaign around the Coronavirus,"This project will ensure as many people as possible have access to straightforward, clear information, that quickly responds to the questions and confusion people have about the coronavirus and the ways in which it is impacting their own lives and those they love. In order to reach millions of people around the world, the project will create high quality, embeddable content that newsrooms, platforms, health authorities, government bodies can all share with their audiences. It will also galvanise engaged citizens, who want to help, by creating an 'army' of 'Information Volunteers' who can take the same content and push it out to their own networks, whether that's via WhatsApp groups, Facebook communities, or family email chains. This crisis has demonstrated that there is no time or resource for duplication. By sharing efforts to monitor trending misinformation, collect real-time questions and areas of confusion from the public, and centralizing the output of shareable 'cards' that respond to these rumours and questions, it will help over-stretched newsrooms and communication departments, and provide concerned citizens with a role to play during a time where they want to help their communities.",2020,2021,First Draft,323960,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C09335,221495/Z/20/Z,The role of research and reflection in third sector responses to complex and fast-changing contexts: Using action learning methodologies to examine responses to supporting people with complex needs during Covid-19 and implications for future practice,"There is a growing recognition within public and third sector organisations that outcomes-based commissioning and management ignores the complexity (at an individual, organisational and systems level) in which services operate. Some in the sector are experimenting with more developmental, collaborative, place-based approaches. However strategic development has recently been disrupted by Covid-19, which has forced services to change overnight whilst increasing support needs within communities. This project will analyse the ways in which community organisations have evolved during the crisis, and identify implications for future practice, not only in terms of service delivery models but also change processes and evaluation methods. CoLab is a cross-sector 'wellbeing hub' hosting 30 organisations from community, social enterprise and public sectors supporting people with complex needs (e.g. homelessness, mental ill-health). As an embedded researcher I will work with staff and users as co-researchers, drawing on research tools from different methodological approaches (e.g. participatory action research, ethnography, developmental evaluation) to explore their experiences of using, delivering and adapting services in a rapidly changing context. Key goals include producing recommendations for service development, identifying appropriate research methods to sustain an 'action research' culture moving forward, and sharing learning more widely within the sector and related academic fields.",2020,2021,University of Exeter,30085.9,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09336,PINV20-107,Study of cardiovascular events in patients with SARS-CoV-2 infection,,2020,-99,Universidad Nacional de Pilar - UNP,125863.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Clinical characterisation and management,Disease pathogenesis, +C09337,PINV20-304,Wastewater epidemiology to quantify and predict SARS-CoV02 levels in the population,,2020,-99,Fundación Facultad de Ciencias Quimicas,42000,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Epidemiological studies,Disease transmission dynamics, +C09338,PINV20-399,"BCG vaccination coverage, Dengue history and COVID-19 incidence in Paraguay",,2020,-99,Salud y Nutrición - Paraguay SRL,10449.25,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Epidemiological studies,Disease surveillance & mapping, +C09339,PINV20-239,Study of the transmission dynamics and genetic variability of circulating SARS-CoV-2 in Paraguay through viral genome sequence analysis,,2020,-99,Centro de Estudios y Formación para el Ecodesarrollo - ALTER VIDA,42000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics", +C09340,PINV20-90,Predictors of severe evolution and mortality in hospitalized COVID19 patients in Paraguay in 2020,,2020,-99,Fundación Centro de Información y Recursos para el Desarrollo - CIRD,42000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Clinical characterisation and management,Prognostic factors for disease severity, +C09341,PINV20-120,Proposal for community intervention to improve hygiene and protection habits during the supply and handling of products from the basic basket to reduce the spread of the SARS-CoV-2 virus,,2020,-99,Universidad Nacional de Pilar - UNP,42000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C09342,PINV20-403,Coronavirus versus urban informality,,2020,-99,"Facultad de Arquitectura, Diseno y Arte - FADA - UNA",42000,Unspecified,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,,, +C09343,PINV20-58,Analysis of the behavior of rural communities to face the COVID-19 pandemic,,2020,-99,Asociación Pro Cordillera San Rafael - PRO COSARA,16644.6,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C09344,PINV20-353,Self-efficacy as a means to strengthen the adoption of health behaviors in vulnerable populations during a pandemic,,2020,-99,Universidad Metropolitana de Asuncion - UMA,42000,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C09345,PINV20-235,Primary Health Care: role of the first level of care during the COVID-19 epidemic and endemic,,2020,-99,DECIDAMOS. Campana por la Expresión Ciudadana,37800,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery", +C09346,PINV20-282,Justice in times of pandemic,,2020,-99,Centro de Estudios Juiciales - CEJ,36680,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Secondary impacts of disease, response & control measures",Social impacts, +C09347,PINV20-362,Identification and promotion of good practices that reduce the possibilities of the spread of the coronavirus in families participating in the Tekopora Program in rural areas,,2020,-99,Fundación Centro de Informacion y Recursos para el Desarrollo - CIRD,22868.79,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions, +C09348,PINV20-139,Verification of the sanitary conditions of popular pots and related initiatives emerging during the COVID-19 pandemic in Paraguay. A guide to its application,,2020,-99,Universidad Privada del Este - UPE,35960.82,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C09349,PINV20-226,Intercultural approach to risk management in the face of the health emergency due to COVID-19 in indigenous communities in the eastern and western region of Paraguay,,2020,-99,Gestion de Desarrollo Social,41720,Other,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Community engagement | Communication", +C09350,PINV20-387,Efficacy of home intervention strategies in patients with COVID-19: a randomized clinical trial,,2020,-99,Fundación Centro de Información y Recursos para el Desarrollo - CIRD,89666.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase)", +C09351,PINV20-273,"Technology and women in pandemic contexts: digital strategies for violence prevention, strengthening economic empowerment and reducing the spread of COVID-19",,2020,-99,Fundacion Capital Paraguay - Fundak Paraguay,41697.6,Human Populations,Unspecified,Unspecified,Unspecified,Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,Gender,,,Paraguay,Paraguay,"Secondary impacts of disease, response & control measures | Infection prevention and control",Social impacts | Economic impacts, +C09352,PINV20-338,"Socio-educational competencies of teachers in situations of health crises (COVID 19 case), in Paraguay",,2020,-99,Universidad La Paz - UNIPAZ,33600,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Secondary impacts of disease, response & control measures",Social impacts, +C09353,PINV20-9,Digital technology to optimize mental health and well-being in chronic patients during the COVID19 crisis in Paraguay,,2020,-99,Universidad Autonoma de Encarnacion - UNAE,37868.95,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C09354,PINV20-343,Implementation of Telepsychiatry in Paraguay: Mental health care in times of COVID 19,,2020,-99,Universidad Politecnica y Artistica - UPAP,41860,Human Populations,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,Digital Health,,,Paraguay,Paraguay,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C09355,PINV20-337,CoVIDA: Repositioning drugs for the treatment of COVID-19 using Artificial Intelligence,,2020,-99,"Centro de Ingenieria para la Investigacion, Desarrollo e Innovacion Tecnologica - CIDIT - Campus Asuncion - UC",43624,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Therapeutics research, development and implementation",Pre-clinical studies, +C09356,PINVO20-6,"In vitro screening of national natural products with antiviral activity, capable of inhibiting the entry of SARS-CoV2 into the cell",,2020,-99,Fundacion Facultad de Ciencias Quimicas,61600,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Therapeutics research, development and implementation",Pre-clinical studies, +C09357,PINV20-287,"Detection of SARS.CoV 2 with GeneXpert in patients of the Pediatric General Hospital ""Niños de Acosta NU""",,2020,-99,Salud y Nutricion - Paraguay SRL,81886,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09358,PINV20-322,Evaluation of spray disinfection devices used to prevent the spread of COVID-19,,2020,-99,Promocion para el Desarrollo - PROPADE,49000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C09359,PINV20-352,Implementation of a Test Laboratory for National Lung Ventilators,,2020,-99,Facultad de Ingenieria - FIUNA - UNA,70000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Research on Capacity Strengthening,Institutional level capacity strengthening, +C09360,PINV20-271,"Comprehensive Planning and Management of the COVID-19 Pandemics in Paraguay: Importance of the integration of epidemiological, economic and social analytical tools",,2020,-99,Desarrollo Institutio de Capacitación y Estudios,42000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Epidemiological studies,Impact/ effectiveness of control measures, +C09361,PINV20-40,Simulation of epidemiological models for prediction and contingency of COVID-19,,2020,-99,Universidad Autonoma de Asuncion - UAA,41678,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Epidemiological studies,Disease transmission dynamics, +C09362,PINV20-140,Results of convalescent plasma administration to COVID-19 carriers,,2020,-99,Facultad de Ciencias Medicas - FCM - UNA,37800,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Clinical characterisation and management,"Supportive care, processes of care and management", +C09363,PINV20-248,COVID 19 infection: age-stratified population-based cohort seroepidemiological study in asuncion and central,,2020,-99,Centro de Estudios y Formación para el Ecodesarrollo - ALTER VIDA,42000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility, +C09364,PINV20-129,Development of a surveillance system to identify probable cases of COVID-19,,2020,-99,Universidad Autonoma de Asuncion - UAA,50400,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,,, +C09365,PINV20-184,A methodology and tool for the management of safe spaces based on group controls and follow-up with contacts,,2020,-99,Centro de Desarrollo Sostenible S.A - CDS,65474.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Americas,,,,Paraguay,Paraguay,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C09366,PINV20-292,Detection and georeferenced monitoring of high-risk patients with chronic diseases at risk of COVID-19 through a mobile application,,2020,-99,Facultad Politecnica - FPUNA - UNA,10254.35,Human Populations | Other,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Consejo Nacional de Ciencia y Tecnología (CONACYT),Paraguay,Americas,Americas,Unspecified,,,,Paraguay,,Epidemiological studies,Disease susceptibility, +C09367,1.04301E+13,Renal patients COVID-19 vaccination (RECOVAC) consortium,,2021,2024,Universitair Medisch Centrum Groningen,3677898.91,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Vaccines research, development and implementation",,2021 +C09368,1.04301E+13,Immunity against SARS-CoV-2 in immune-suppressed patients: increased risk of insufficient immunological memory or sufficient protection against re-infection - a Target to B! substudy,"In general, vaccine responses are variably reduced in a large group of patients with autoimmune diseases (AID), mostly depending on the type and dose of the used immunosuppressive treatment (s). Currently, there is the pressing question whether vaccination against SARS-CoV-2 is less effective in these patients with immunosuppression (ISP). The main objective of this vaccination study is to elucidate whether the efficacy of SARS-CoV-2-targeted vaccination is reduced in ISP compared to patients with AID without immunosuppressive drugs or healthy individuals, and whether the persistence of SARS-CoV-2-specific immunity differs over time because of ISP. To get much better informed and prepared regarding current vaccination strategies, we will use the unique platform of our T2B consortium, a well-established close collaboration and infrastructure of 6 different academic hospitals, Reade, RIVM and Sanquin Blood Supply Foundation. Building on several clinical studies already initiated at the start of the SARS-CoV-2 pandemic by our clinical T2B partners, we will perform in-depth analysis of the humoral and cellular vaccine-induced immunity against SARS-CoV-2. In one of our previous prospective observational studies we focus on the longevity of the immune response in ISP after primoinfection and the role of this previous infection in the early vaccine response. In the current vaccination study in AID, we will collect longitudinal clinical data and samples from selected 3000 patients treated with frequently prescribed immunosuppressive drugs representing distinct categories within the wide spectrum of immunosuppression to determine vaccination efficacy in ISP. Humoral response in ISP upon vaccination will be compared to the humoral response in 1000 patients diagnosed with similar AID but without immunosuppression as well as to the response in healthy controls. In addition, we will determine the safety of vaccination and changes in disease activity of the underlying AID after vaccination (disease flaring), by comparing to a separate control group of 1000 patients with similar AID that are not willing to be vaccinated. Together with our previous objectives,",2021,2023,Amsterdam UMC - location AMC,2807874.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C09369,1.04301E+13,VOICE: Vaccination against cOvid In CancEr,"RESEARCH QUESTION In patients with cancer, the disease and immunotherapy and chemotherapy may significantly impact the ability to develop an effective immune-response to COVID-19 vaccination and could even increase the risk of adverse events. OBJECTIVE To assess immune-response and adverse events after vaccination with one vaccine against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy.",2021,2023,Universitair Medisch Centrum Groningen,3626819.6,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +C09370,1.04301E+13,Vaccination Against Covid in Primary Immune Deficiencies,"Background and research question: Primary immune deficiencies (PIDs), also known as Inborn Errors of Immunity (IEI), are clinically characterized by an increased risk of severe infections. Therefore, these patients may also have an increased risk of adverse outcome of COVID-19 or may experience protracted course of disease. Effective SARS-CoV-2 vaccination would therefore be of great clinical importance in PIDs. However, until now not much is known about the efficacy and safety of SARS-CoV-2 vaccination in these vulnerable patients. In PID patients, the underlying disease may have a significant impact on the ability to develop an effective immune response after SARS-CoV-2 vaccination. Therefore this study aims to assess efficacy and safety of SARS-CoV-2 vaccination in patients with various forms of PID Hypothesis: PID patients show diminished B and T cell response after SARS-CoV-2 vaccination and these patients require intensified vaccination regimens",2021,2023,Erasmus MC,1372391.85,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +C09371,1.04301E+13,Investigating the immune response to COVID-19 VAccination in Lung Transplantation patients (COVALENT study),"Lung transplantation patients are immunocompromised due to antirejection therapy. The effectivity of the COVID-19 vaccination in this high-risk patient group is completely unknown. Objective: To investigate the humoral and cellular immune response, and the development of immunological memory to the COVID-19 vaccination in lung transplantation patients. To clarify firstly if immunity develops in these patients and secondly, if the immune response lasts for 1 year. This is an observational study of the development of humoral and cellular immune responses following COVID-19 vaccination. Baseline samples are taken from participants prior to first vaccination, and these participants are sampled at regular intervals, until a year after vaccination. A group of patients who are on the lung transplant waiting list are immunized and followed at regular intervals. Following transplantation, the observation time is extended to six months after transplantation. Patient characteristics, potential side effects of vaccination, lung function and degree of immunosuppression will be collected.",2021,2024,Universitair Medisch Centrum Groningen,758327.4,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +C09372,1.04301E+13,Prospective monitoring of antibody response following COVID-19 vaccination in people with Down syndrome (PRIDE study),"The risk of severe course of SARS-CoV-2 infection in people with Down Syndrome (DS) is substantially increased. The risk of death is 3-10 fold higher than in healthy people. COVID vaccines have been registered but none of them have been studied in people with DS. Vaccine responses in people with DS are suboptimal, probably related to the partial immune deficiency in DS characterized by - among other things - a lack of naïve T-cells. In this study (PRIDE), we aim to assess the immunogenicity of SARS-CoV-2 vaccination in patients with DS. OBJECTIVES Primary objective: to assess the antibody response after mRNA SARS-CoV-2 vaccination in people with Down Syndrome.",2021,2024,Universitair Medisch Centrum Utrecht,1235330.42,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C09373,1.04301E+13,A phase I study on the pharmacokinetics of anti-SARS-CoV2 virus neutralizing antibodies in middle aged and elderly volunteers. Towards evidence-based dosing of convalescent plasma for COVID-19,,2021,2021,Erasmus MC,155050,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Therapeutics research, development and implementation",Phase 1 clinical trial,2021 +C09374,1.043E+13,"Towards a population-based approach to prevention, care and support by identifying vulnerable groups as a result of the COVID-19 pandemic and response measures","Project description The corona virus and the measures taken have major consequences for the health of the Dutch population. The consequences are not evenly distributed and not always clearly visible. Vulnerable groups in particular are less well identified. This is important in order to have the complete picture in order to find the balance between what the control measures yield (health gain) and costs (health loss). The following objectives are central to this project: Gaining insight into which groups are vulnerable to the Corona measures and why Looking for good examples to recognize early when vulnerability arises and ways to prevent it. This is done by looking in various neighborhoods in the province of Utrecht to see which good examples there are already, and what needs to be developed in order to stay healthy. Ensuring that the knowledge of objectives 1 and 2 can also be used in other places, for example in other cities, in other countries and in (care) training courses.",2020,2022,GGD Region Utrecht,,Human Populations | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Research to inform ethical issues,"Disease susceptibility | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2020 +C09375,844001805,"Grieving in Corona Times: Possibilities, Limitations, and Opportunities to Prevent Complicated Bereavement in Survivors: Descriptive Research and Implementation.","The corona pandemic also has consequences for next of kin. The strict guidelines on ' social distancing ' and not being allowed to comfort physically make the farewell different from what people want, expect and are used to from culture, religion or tradition. This may mean that the farewell, rather than comforting, is traumatic, which can lead to 'complicated grief'. This applies not only to relatives of corona victims, but to all relatives who lost a loved one during the pandemic. Research Questionnaires and filmed interviews among a large group of relatives describe the consequences and the experience with solutions in the short, but certainly also the longer term. Expected results In addition to the research results, there will be a website (films, tips & experiences), a documentary and an e-learning module. Expected impact The project group (with regional, cultural and religious distribution) hopes to reduce the chance of complicated grief.",2020,2022,Locomotion,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09376,1.04301E+13,Convalescent plasma as a treatment for high-risk outpatients administered within 7 days after COVID-19 disease onset (CoV-Early),"Project description The CoV-Early study investigates whether plasma administration of ex-corona patients leads to a faster recovery in corona patients who have not yet been admitted to hospital. Because previous research in the Netherlands showed no benefit from treatment with plasma at a later stage of the disease (in hospital), we administer it quickly in this study (at the latest seven days after the onset of the disease). Research In this study, one group of patients will receive plasma with antibodies and a second group, the control group, will receive plasma without antibodies against the coronavirus. This is necessary in order to be able to reliably investigate the effectiveness of plasma. To participate, a patient must be at least 70 years old or 50 to 69 years old and also belong to a risk group. The study is coordinated by Erasmus MC and LUMC and was set up in collaboration with Sanquin.",2020,2022,Erasmus MC,2701572,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Clinical trials for disease management,2020 +C09377,844001804,An eye for loved ones at the time of the COVID-19 pandemic: an additional module COVID-19 for and aftercare for loved ones around the death of a loved one (further development of the ZonMw Eye for Relatives method),"Project description At the end of 2019, a methodology became available from the Palliantie project Oog voor Naasten (OvN) that enables care providers to provide targeted care to their loved ones before and after the death of their loved one. We are further developing this OvN method in the ON2 project (duration 2021-2023). The corona pandemic changed care, with consequences for the wellbeing of the families of patients who die from COVID-19. It is feared that measures to keep a distance will lead to emotional problems in coping with loss. At the end of May 2020, national experts in palliative care based on the OvN method compiled a specific COVID-19 module for use with family members of patients with COVID-19. Research In this project, we are improving the current COVID-19 module by investigating what care they need before and after the death of their loved one with COVID-19. We also look at the impact of measures on COVID-19 on care for loved ones and which good examples have been developed in the recent period. Expected results We use the information to improve the current COVID-19 module, so that the knowledge gained in the past crisis can be used for future ones. The module will be included in the ON2 project that will be made suitable for various settings (home, hospital, nursing home, etc.) and target groups until 2023. Expected impact The improved COVID-19 module supports caregivers to provide appropriate care for loved ones.",2020,2022,Leiden University Medical Center,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Indirect health impacts | Individual level capacity strengthening,2020 +C09378,50-56300-98-1588,"Risk maps for public buildings as a basis for prevention measures for aerogenic SARS-COV-2 transfer: interaction of occupancy, temperature control and ventilation",,2020,2021,Saxion University of Applied Sciences,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C09379,1.043E+13,The impact of the COVID-19 outbreak on the diagnosis and treatment of cancer patients: lessons for the future,"Project description The project examines the impact of the COVID-19 outbreak on the care of people with symptoms of cancer and people with cancer. Detection and care of cancer patients may have been different and less successful during the COVID-19 outbreak. To prevent this in the event of a subsequent outbreak or comparable major health crises, the following questions are answered: How big was the impact of the COVID-19 outbreak on cancer detection? Why were cancer diagnoses made later and how can we prevent it? How has the care been adapted and what is the effect of this on the quality of care? How can this be better next time? 'Lessons for the future' are formulated to ensure an optimal balance between changes in care required by COVID-19 and the quality / availability of care for people with cancer.",2020,2022,Netherlands Comprehensive Cancer Organization (IKNL),553854.58,Human Populations,Unspecified,Unspecified,Not applicable,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C09380,1.043E+13,RAS inhibition for the prevention of Acute Respiratory Distress Syndrome (ARDS) in patients admitted with a COVID-19 infection,"Project description The COVID-19 pandemic causes high morbidity and mortality because COVID-19 infection can cause acute lung damage and be complicated by severe acute respiratory distress syndrome (ARDS). The renin-angiotensin system (RAS), a well-known cardiovascular cascade, has also been shown to play a role in the development of ARDS. It is believed that the COVID-19 virus consumes the enzyme ACE2. This is an enzyme that normally breaks down angiotensin-II (ANG-II). Reduction of ACE2 can cause an accumulation of ANG-II, which can lead to acute lung damage with IC admissions and possibly death. Research It is hypothesized that RAS inhibition by ACE inhibitors and angiotensin receptor blockers, such as, for example, lisinopril and valsartan, respectively, may reverse the development of acute lung damage and ARDS in hospitalized COVID-19 patients, thereby preventing IC admissions and death.",2020,2022,Netherlands Heart Institute,553877.84,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management",2020 +C09381,1.043E+13,"The impact of COVID-19 among low-literate people and people with MID: measures, (mental) health and action perspectives with regard to the care and support needs and policy","Project description In order to gain insight into the impact of the pandemic, RIVM, together with the GGDs, is conducting national research to map out how the population is doing (physical, psychological and social) and how this will develop over time. However, the aforementioned research does not reach low-literate people and people with mild intellectual disabilities. This project focuses on gaining insight into the impact among these target groups and answering the following questions: To what extent are the pandemic and the national measures understood and monitored? What is the impact of the pandemic on (mental) health? Which action perspectives can be formulated for supporters and municipalities? The goal is to develop a simple questionnaire for these target groups. The questionnaire will be derived from the national questionnaire and deployed at three times. The results are interpreted with different disciplines and translated into concrete action perspectives",2020,2022,Safety and Health Region Gelderland-Midden,256821.27,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C09382,1.043E+13,Impact of the COVID-19 pandemic on patients with inflammatory rheumatic disease,"Project description Target The main aim of this study is to investigate whether infection with SARS-CoV-2 develops differently in patients with a rheumatic disease compared to healthy control participants and what the effect of immunosuppressive medication is on this. The focus is on the severity of the disease of COVID-19, differences in the development of immunity against SARS-CoV-2 and the effect of the pandemic on quality of life. Method Patients with a rheumatic disease are approached to participate in the study. Each patient is asked if he / she wants to enroll a control participant who does not have a rheumatic disease, is of the same sex and is approximately the same age (<5 years difference). In a period of approximately 6 months, both groups will be asked 3 times to complete a questionnaire and to have blood taken twice. The body material obtained will be tested for the presence of antibodies against SARS-CoV-2.",2020,2022,Reade Research BV,307862.7,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +C09383,1.043E+13,Initiative COVID Data (INCODA),"Project description We are moving from a national and uniform COVID-19 crisis approach to a differentiated approach. This requires more insight into epidemiology, transmission, medical progress and burden on the healthcare system. This is necessary to predict the course of the pandemic and to support decisions about measures. The objectives of the 'COVID Data Initiative' (INCODA) are: Designation of groups with a high risk of a COVID-19 infection with a severe course Investigate whether the combination of medical characteristics and clinical parameters with geographic, demographic and socio-economic characteristics is valuable and can be used for secondary prevention measures and the selection of treatment methods INCODA does this by: Combining clinical and IC admission data from COVID-19 patients with CBS data Identifying risk groups based on a multivariable profile and developing prediction models for the risk of severe course of COVID-19 Investigate possible interventions",2020,2021,Amsterdam Health and Technology Institute,239316.93,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Disease pathogenesis | Supportive care, processes of care and management",2020 +C09384,1.043E+13,Primary care research on outcomes of COVID-19 (PRO-COVID-19),"Project description Many research initiatives have emerged since the global spread of COVID-19; these take place almost exclusively in secondary care institutions. In the Netherlands, however, most patients initially contact their GP. Well-organized primary care, including Corona specialist GPs, can optimize referral to emergency care, reduce pressure on hospital capacity and provide adequate follow-up for COVID-19 patients. The acute assessment of COVID-19 patients in general practice is challenging. Furthermore, the long-term impact of COVID-19 patients, both somatic and psychological, within primary care is unknown. Research This study aims to study the effects of two research questions, related to the visit of COVID-19 suspected patients to the GP / GP Coronapost: What clinical signs and symptoms from the medical history, physical examination, and diagnostic tests predict COVID-19-related hospital admissions within 2 weeks? What are the long-term consequences of more serious COVID-19 infections (complicated respiratory tract infections) in patients who have attended the general practice?",2020,2022,University of Maastricht,411229.23,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +C09385,1.043E+13,An unexpected false start on the job market,"Project description The COVID-19 pandemic and the measures taken are affecting the economy. Government measures to limit unemployment are temporary in nature and mainly aimed at preserving existing jobs. Young people who are now entering the labor market or who have recently started a flexible job hardly benefit from this. Young people in a vulnerable position, for example because they are ill, are likely to be hit harder. As a result, the inequality of opportunities between groups of young people is further increasing. Based on administrative data, it is shown which groups of young people are hit hardest in the labor market by the corona crisis. Subsequently, these young people are spoken to and work sessions are organized with policymakers, professionals and young people. This provides more insight into the obstacles experienced by young people and suitable interventions to support young people. The acquired knowledge is shared in an accessible way, so that the results can be used in practice.",2020,2022,SEO Economic Research,413190.57,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09386,1.043E+13,EVER - Economic Resilience of Regions,"Project description The global corona crisis has major economic and social consequences, which have different effects in each region. With this research project, regional stakeholders learn from each other, using scientific insights about the effects of the crisis and interventions. To what extent and how are regions affected by the corona crisis and are regions able to recover? Which regions are able to get out of the crisis even better? This research project consists of three parts. First, scientific research into regional variation in ecosystem resilience for entrepreneurship. Second, an online data dashboard in which existing data sources are made available and relevant to regional stakeholders in real time. Third, decision-makers in sectors and regions are brought together to share experiences and jointly gain new insights, through a so-called Platform of Practice.",2020,2022,University of Utrecht,546381.05,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09387,1.043E+13,Is our environment future-proof for sufficient physical activity in a 1.5m society?,"Project description Our living environment is not designed to keep 1.5 meters away. Since March 2020, a decrease in exercise patterns can also be seen. An inactive lifestyle is a predictor of health problems. Therefore, the expected long-term health effects of COVID-19 will be stronger in less active neighborhoods. These are often neighborhoods with a low income and education level. Research Active physical activity is monitored in various lockdown stages through ongoing medical studies. Outdoor spaces where movement patterns decrease the most are investigated by means of an urban development analysis. Together with 12 municipalities, interventions are being investigated that make the outdoor spaces more suitable for a healthy 1.5 meter society. Expected outcomes A measuring instrument for the mobility-friendliness of the living environment: the Beweegplekmeter, an intervention package for municipalities and a GGData platform addition that provides insight into spatial bottlenecks and solutions.",2020,2022,Radboud University Nijmegen,515654.95,Human Populations | Environment,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09388,1.043E+13,Opportunities in Crisis: how do schools shape educational partnership?,"Project description Resilient schools The COVID-19 crisis means that schools must respond resiliently. They have to adapt quickly to unforeseen circumstances. The big challenge is to simultaneously maintain the quality of education. Disadvantaged students run the most risks here. There is a great risk that they will develop even greater educational disadvantages during this period. Strengthening cooperation with parents of underprivileged students The resilience of schools in secondary education (VO) will be studied over the next two years: how will schools now enter into cooperation with parents of underprivileged students and how can they strengthen this? Developing and testing interventions The research takes place in the regions of Amsterdam and Nijmegen. The study is conducted in three phases. After each phase, insights are immediately shared with secondary schools in the Netherlands. In the second year, the first findings are used to develop and test interventions in collaboration with schools.",2020,2022,University of Amsterdam,546265.16,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09389,1.043E+13,Critical materials in crisis,"Project description The provision of critical materials such as mouth masks, respirators and testing was (and remains) crucial during the pandemic. The presence of these critical materials (timeliness, quality and quantity) turned out to be a bottleneck for the care capacity. Different countries have dealt with this differently and now have different strategies for the second wave and a new pandemic. Examples are the development of a national manufacturing industry and the stockpiling of iron stocks. The aim of this research is to learn from an international comparison of the different strategies in the COVID-19 crisis. The Dutch approach to material supply is compared with that of 23 other countries. Within the Netherlands, this takes place on a national level, but also in various institutions in the cure (hospitals) and care (including nursing homes) sector. The results are expected at the end of 2021.",2020,2021,PPRC BV,413989.29,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09390,1.043E+13,Inequality in sport and exercise under COVID19: The impact of sport on a resilient society,"Project description After education, the sports sector was the first to start after the 'lockdown'. Sport is considered important to mitigate problems as a result of the corona measures and thus contribute to a resilient society. But how can citizens be active? After all, poverty, care tasks, social isolation and / or health issues - caused or reinforced by the corona measures - can experience (too) high barriers to participation in sports and exercise. That is why changes in sports and exercise behavior of the population and of specific target groups are studied to see whether social inequality in sports is increasing or decreasing. In addition, the experiences of the specific target groups during COVID-19 and the effectiveness of policy efforts to enable everyone to participate and to optimize the social value are also discussed. Together we are able to come up with guidelines for a society in which everyone can (continue to) participate in sports and exercise.",2020,2023,Radboud Universiteit Nijmegen,524394.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09391,1.04301E+13,Bacillus calmette-guérin vaccination to prevent serious respiratory tract infection and covid-19 in vulnerable elderly - an adaptive randomized controlled trial (bcg-prime),"Project description There are indications that the vaccine against tuberculosis (the BCG vaccine) reduces the risk of developing respiratory infections by temporarily boosting the immune system. Elderly and chronically ill patients have an increased risk of a serious coronavirus infection. Research and expected outcomes The BCG-PRIME study is investigating the extent to which the BCG vaccine protects vulnerable elderly patients against a coronavirus infection or a clinically relevant respiratory tract infection by another pathogen. Participants are 60 years of age or older and are receiving treatment in hospital or at the thrombosis service. They are assigned BCG or a placebo by drawing lots. After that, they keep a diary about respiratory complaints for six months using a smartphone app, or they pass this information on by telephone. The study is being carried out in 22 hospitals in the Netherlands, including the seven teaching hospitals and the seven top clinical hospitals united in Santeon, and is coordinated by UMC Utrecht.",2020,2022,Universitair Medisch Centrum Utrecht,17866577.16,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Prophylactic use of treatments | Phase 3 clinical trial",2020 +C09392,1.043E+13,Learn to dance. Management of care in times of a pandemic.,"Project description Corona hits us all hard. Particularly in the healthcare sector, an enormous response has been initiated to receive sometimes very sick people. Outside of healthcare, almost everyone has to deal with the measures. The quality of decision-making in a crisis like this is of great importance. Research This project focuses on the organization of decision-making. Looking back, we want to learn from the first and second waves of the pandemic. Looking ahead, we try to learn lessons with the actors involved. The starting point is that some form of 'adaptive management' is required; a board that can adapt to unexpected and uncertain circumstances. The virus will be with us for a long time and that means we have to learn to live with it. We use the metaphor of dance to give meaning to this adaptive way of dealing with the virus. How can we learn to dance (better)? We hope to contribute to this by following decision-making processes and reflecting on them together with those involved.",2020,2022,Erasmus Universiteit Rotterdam,332148.91,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C09393,1.043E+13,Child and adolescent mental health and wellbeing in times of the COVID-19 pandemic; Elucidating intervention targets to decrease mental health problems and optimize wellbeing in Dutch children with and without a history of mental problems.,"Project description Children and young people are less vulnerable to the medical consequences of COVID-19. Yet the corona measures will also hit them hard. However, stories are also heard about children and young people who experience the corona measures as pleasant. They benefit from the peace, structure and reduction of pressure that normal life entails. In this project, large samples of Dutch children and young people (with and without previous mental problems) are systematically investigated what the effects of the corona measures are on their mental health and well-being. The findings will result in recommendations for prevention and interventions at the national, regional and individual levels. Children and young people will be actively involved in this research. By carefully charting the consequences of the corona measures on the mental health of Dutch youth, it is hoped to be optimally prepared for future developments in the pandemic.",2020,2022,Amsterdam UMC - locatie VUmc,545929.52,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09394,1.043E+13,POLAR: Psychosocial effects of corona measures in people with Alzheimer's,"Project description POLAR aims to make people with Alzheimer's more resilient to the consequences of the corona measures. They have a hard time during corona. Not only are patients more susceptible to the virus, but informal carers are also hit hard by the measures. Most people with Alzheimer's live at home and use (in) formal care and support networks. Formal care concerns, for example, case management and daytime activities and these have often been stopped due to the measures. The pressure on the informal caregiver has increased considerably as a result. POLAR maps the effects of corona on behavior, mood and functioning of the patient, burden on the family and use of care. In addition, online information tools are being developed on how to deal with the consequences of the corona measures. This contributes to positively influencing the support system around people with Alzheimer's during and after COVID-19. POLAR is a collaboration of Alzheimercentrum Amsterdam, Amsterdam UMC, Alzheimer Nederland and Pharos.",2020,2022,Amsterdam UMC - locatie VUmc,306421.38,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09395,1.043E+13,Corona measures: 'double jeopardy' for reading performance of target group students in primary education?,"Project description Due to the corona crisis, all schools were closed on March 16, 2020, forcing schools to organize distance learning. This modified way of working may have had a negative impact on the learning process and learning outcomes of students, especially in the area of ​​reading skills. It is also possible that this negative influence is greater for certain groups of pupils than for other pupils, which further increases the inequality of opportunities. This research project will map out the extent to which target group students from the educational disadvantage policy are hit extra hard by the corona measures and what lessons can be learned for future, comparable situations.",2020,2022,Expertisecentrum Nederlands,267602.38,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09396,1.043E+13,Is COVID-19 a threat to banks and financial stability in Europe?,"Project description The COVID-19 pandemic has a huge impact on the economy. The world economy is expected to contract by no less than 5% in 2020, even more than during the 2008-2009 financial crisis. The length and depth of this recession will depend to a large extent on the impact of COVID-19 on banks, given their central role in the economy. However, this impact is difficult to assess, because banks estimate the losses on their outstanding loans based on outdated accounting data. Banks and regulators urgently need an up-to-date estimate of expected losses from COVID-19, so that they can take action when financial stability is at stake. In this project, a new method is being developed to estimate these losses in real-time based on market valuations and the option evaluation model of Nobel Prize winner Robert Merton. The method is applied to European banks and the market valuations of 1,981 European listed companies in 19 sectors.",2020,2022,Erasmus University,87387.47,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C09397,1.043E+13,LAMP-based molecular diagnostics or SARS-CoV-2,"Research The method is based on the so-called loop-mediated isothermal amplification (LAMP) technology. LAMP testing is simpler than the standard PCR method currently in use and is also suitable for performing at sample collection locations. The LAMP test can be performed in parallel with the existing PCR tests and can thus increase the test capacity in the Netherlands. In this project TNO is collaborating with DSM, RIVM, LUMC, UMCG and Micronit on a LAMP test that is less dependent on suppliers of critical reagents. In addition, TNO, in collaboration with the GGD Amsterdam, will accelerate the clinical validation of the LAMP diagnostics and implement it on an existing test street. Expected outcomes This study is working towards a LAMP-based test method for COVID-19, whose materials and reagents will not be pressurized, a comprehensive clinical validation and an implementation plan for large-scale use of LAMP tests in the Netherlands.",2020,2021,TNO,418571.65,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09398,1.043E+13,Running ahead of the tsunami: how mobility and behavior can give a quick indication of a second COVID-19 wave,"Project description Who: Consortium of experts in public health, eHealth, behavioral sciences, mathematical epidemic modeling, governance and data analytics. What: Interactive dashboards are being developed to support decision-making about local lockdowns. These dashboards are complementary to the dashboards developed by the Dutch government, because they contain new types of information: regional, current trends in risky behavior, and mobility between regions. When: October 2020 - March 2022. The first prototype dashboards will be available in early 2021. How: Mathematical models are used to quantify risk predictions and to develop an early warning system in the form of interactive dashboards. To achieve implementation, the response of policy makers is used as input to improve the dashboards. Why: This project helps in making informed regional decisions in a timely manner to contain the spread of the virus.",2020,2022,Technische Universiteit Eindhoven,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies,Disease transmission dynamics,2020 +C09399,1.043E+13,Social impact of COVID-19 on vulnerable groups on the CAS islands,"Project description The COVID-19 pandemic has strained the economies, health-care systems, social structures and living standards on the islands Curaçao, Aruba and St. Maarten. Using a human rights-based approach this multidisciplinary study will focus on the social impact of the COVID -19 pandemic and the State responses towards protecting vulnerable families. We apply a multi-sited, mixed-methods approach to understand the various reasons that contribute to increase in vulnerability and measures that can be taken to build social resilience among families and communities. This study will also evaluate the performance of COVID-19 measures and make recommendations for futures outbreaks and epidemics.",2021,2023,Curacao Biomedical & Health Research Institute,279655.67,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C09400,1.043E+13,Ethnic inequality in COVID-19,"Project description Figures from the United Kingdom and the United States show that among certain migrant groups, COVID-19 is more common and more serious. This inequality is probably related to the higher prevalence of disorders such as diabetes due to obesity, an overrepresentation in essential professions (e.g. nurses), lower level of education, a less good command of the language of the country in which they live, living conditions and ways of getting help. search (for example, fear of being infected in a hospital). The planned study will show the occurrence and severity of COVID-19 differences between migrant groups and the native Dutch. The number of cases of infection and disease outcomes will be investigated through an ongoing large Amsterdam study among migrant groups: the HELIUS study. In this study, supplemented by other smaller-scale studies, information is collected on how information about the measures against dispersal reaches these migrant groups and whether they follow the advice. In addition, the impact of these measures on individual lives, in particular on well-being and use of non-COVID health care, is examined. With this study, the seriousness and consequences of the pandemic for migrant groups in the Netherlands can be made clear. In this way, possible starting points for policy and any need for specific measures become clear, with the aim of reducing the number of infections and improving the prognosis of those who are infected.",2020,2021,Amsterdam UMC - locatie AMC,558100,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Communication | Indirect health impacts,2020 +C09401,1.043E+13,First-line COVID-19 portal: development of best practices for first-line COVID-19 rehabilitation based on digital knowledge sharing,"Project description In this project, healthcare providers are working with researchers and software developers to develop a COVID-19 portal for primary care. Reason The reason is the relatively unknown patient group that has to rehabilitate at home after a COVID-19 infection in order to resume daily activities. In order to be able to optimally coordinate the care for these patients, the different care providers benefit from insight into the physical, mental and social situation of a patient. Care providers, such as physiotherapists, dieticians and psychologists, therefore want to be able to easily share information about the total rehabilitation of an individual patient digitally. Target The COVID-19 portal aims - with the patient's permission - to allow healthcare providers to view each other's electronic patient files. For example, information about changes in weight and food intake may be of interest to a physiotherapist. The portal contributes to person-centered care.",2020,2021,Hogeschool van Arnhem en Nijmegen,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,Digital Health,,,Netherlands,Netherlands,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C09402,1.043E+13,The effect of COVID-19 on the innovation and corporate venturing activities of organizations,"Project description Target The aim of this research is to determine the effects of the Covid-19 pandemic on the innovation and corporate venturing activities of organizations. Which factors determine whether innovation and corporate venturing activities can survive a crisis such as Covid-19? Approach Based on interviews with prominent Dutch companies, this project aims to map out best practices . In this way they can provide companies with tools for innovation management in times of crisis and thus help them to better protect their innovation activities in the future.",2020,2021,Erasmus University,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09403,1.043E+13,Develop a monitoring system and protocols to contain new outbreaks of COVID-19,"Project description Due to the corona pandemic, a problem is likely to remain until a well-functioning vaccine is available. Controlling new outbreaks until then requires a combination of effective monitoring, along with detection, testing, isolation and quarantine protocols. The aim of this project is to develop a broad scientific basis for an effective monitoring system for COVID-19 with associated action protocols. This is done, among other things, by means of mathematical models. This takes into account the characteristics of COVID-19, the status of the outbreak, potential imports of disease cases, specific risks and target groups, the impact of measures to prevent spread and human behavior. This research is conducted with a large group of experts from various disciplines and health institutes and organizations. The results can be used directly by policymakers for the current pandemic. In addition, the developed methods and models can also be used for future outbreaks of other infectious diseases.",2020,2021,Utrecht University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies,Disease transmission dynamics,2020 +C09404,1.043E+13,ACTE - Phasing out scenarios for corona measures: Transport and economic effects,"Project description This research focuses on the economic and logistical consequences of the 1.5 meter society for the mobility of people. This involves looking at various phasing-out scenarios for corona measures that are possible and obvious for the transport sector with social distancing. Examples include combinations of keeping a distance, reorganizing the public road, individual measures such as face masks, and collective protective measures such as transparent partitioning in public transport and airplanes. The study focuses on aviation, the road network, public transport, cycling and walking. Among other things, the researchers compile an overview of phasing out scenarios and policy measures that are being implemented and proposed in other countries. Promising options are selected for the Dutch context together with Dutch policymakers. These options are then assessed by the Dutch population in a Participative Value Evaluation. This project is carried out by TU Delft and VU University Amsterdam.",2020,2021,Technische Universiteit Delft,111286.42,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09405,1.043E+13,"Conditions for technological solutions in a Covid-19 exit strategy, with particular focus on the legal and societal conditions","Project description Digital solutions can help manage the current Covid-19 pandemic. The current discussion about contact tracing apps in particular also poses new challenges, such as the question of how we can implement these technologies in a way that takes into account both the fundamental rights of the individual and the need for democratic control. This research therefore focuses on the question of which legal, ethical and social conditions must be met for the use of digital solutions in the Covid-19 exit strategy. In addition to an in-depth analysis of legal and social conditions regarding the implementation of digital solutions, use is also made of an empirical study of the perceptions and experiences of users, and the impact on society. The research is led by Prof. Natali Helberger, Prof. Claes de Vreese, Prof. Joris van Hoboken and Prof. Mireille van Eechoud. They are assisted by a group of experts and the interdisciplinary research team of Digital Transformation and Information and Communication & the Data Society , two research initiatives at the UvA.",2020,2021,Universiteit van Amsterdam,111340.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures,2020 +C09406,1.043E+13,What does COVID-19 mean for the employability and resilience of vulnerable employees in facility services?,"Project description Reason The COVID-19 crisis can cause many jobs in facility services to change or disappear. Many of these employees fall under the vulnerable groups. It is important to see how they can be supported. Target The project has two objectives: 1. To provide insight into which strategies within facility services can be used to increase the resilience of employees. 2. Provide insight into which jobs within the sector are the most vulnerable and where, based on existing knowledge and skills, there are opportunities for employees. Approach The project uses insights from economics, psychology and sociology to analyze what the labor market situation means for the well-being of employees, which strategies can be used within the sector to increase their resilience, what knowledge and skills they have built up, and what knowledge and skills are needed to increase their employability for new career opportunities.",2020,2021,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09407,1.043E+13,"The social dynamics of the COVID-19 pandemic: education, socio-economic position and solidarity","Project description The major social effects of the COVID-19 pandemic will not be evenly distributed across society and existing inequalities in society may be exacerbated as a result. A research team from the UvA, EUR and VU will therefore map out the consequences of the corona virus on social inequalities. The research team looks specifically at the areas of work and income, education, social psychological well-being, and mutual solidarity and trust. They will look for social dividing lines, will identify vulnerable groups and formulate policy strategies for strengthening the resilience of individuals, organizations and society. The findings are relevant to society and science. This project is in line with another ZonMw funded project:Social Impact of Physical Distancing on Vulnerable Populations during COVID-19 in the Netherlands . The research is carried out by the University of Amsterdam, Erasmus University Rotterdam and VU University Amsterdam.",2020,2021,Universiteit van Amsterdam,130568.19,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C09408,1.043E+13,Digital visits to people with disabilities: a multidisciplinary substantiated guide for residential locations where relatives are physically prohibited,"Project description The coronavirus has changed the daily lives of people with disabilities. Especially for people who receive long-term care and live in a residential care location: In March residents were suddenly no longer allowed to receive visitors, not even from family. Residents were also not allowed to visit family and friends. The advice was that instead of physically visiting, people could call each other as much as possible. They could therefore see each other via an image connection. This project maps out for whom a 'digital visit' is feasible and attractive. It is also being investigated how residential care locations can support this 'digital visit'. In recent months, a great deal of experience has been gained with various forms of digital visits and preconditions to ensure that this runs smoothly. These experiences are brought together with scientific knowledge in a written guide for customization around digital or non-digital visits if this is not physically possible or permitted.",2020,2021,Vrije Universiteit Amsterdam,216156.15,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09409,1.043E+13,Raw grief: if more residents you care for die than you can handle: How can we take care of you?,"Project description A disturbed grieving process can limit professional functioning. This also applies to professionals in training who do an internship. They are suddenly confronted with several deaths per week of residents they care for during corona time. Approach In this project social workers and MBO enter into a partnership in the field of grief. We are examining what we can learn from the training for carers of the elderly with a view to preventing disturbed grief. To this end, in this project we will analyze the experiences of three directly involved groups; namely students, study career counselors and internship supervisors. This analysis is aimed at identifying factors that influence the personal capacity and professional functioning after the crisis situation. This knowledge leads to a report and advice to involved parties (including national ones) in line with current and possibly subsequent crisis situations.",2020,2021,Hogeschool Utrecht,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09410,1.043E+13,Healthy daytime activities for people with intellectual disabilities in corona times (and beyond),"Project description Reason The COVID-19 (corona) pandemic has major consequences for people with intellectual disabilities (ID). This gives them fear of infection and stress because their regular daily routine is disrupted by limitations in their daily activities as a result of the corona measures. This can cause psychological and behavioral problems. Approach In this project, a daytime provision for people with ID is being developed with a fixed structure aimed at health and well-being. It consists of educational, exercise, experience and cultural activities, individually or in groups, which can be used flexibly depending on the corona measures. The effect of the daytime activities on the quality of life and satisfaction with this is measured with questionnaires. The number of infections with the virus and the application of corona measures are monitored. The project is being carried out by the Academic Workshop on Intellectual Disability and Mental Health in collaboration with local municipalities.",2020,2021,Accare,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2020 +C09411,1.043E+13,Caging the dragon: translational approach to unravel and prevent COVID-19 associated thrombosis,"Project description In COVID-19 patients, the rate of venous thromboembolism (VTE), such as leg thrombosis or pulmonary embolism, is remarkably high, up to 48% in the ICU. The presence of VTE causes more serious illnesses and an increased number of deaths. In addition, VTE occurs despite preventive treatment with blood thinners (heparin). This may indicate heparin resistance or the possibility that heparin treatment is not the (only) solution. In order to find the best possible treatment for COVID-19 patients, the disease process and risk factors must be understood, as well as the safety and efficacy of the currently prescribed thrombosis prophylaxis and treatment. Research The study will study the exact magnitude of the number of VTE cases in the Netherlands and the effect of preventive treatment with heparin, identify risk factors and predict which factors contribute to this. Laboratory research also provides insight into the development of VTE. To distinguish whether VTE in COVID-19 patients is the result of a direct effect of the virus or indirectly via the immune system, a combination of clinical cohort studies with in-depth in vivo and in vitro studies is performed. To predict the risk of VTE in admitted COVID-19 patients, patient data is collected and VTE patients are identified. Dynamic prediction models are developed and individual VTE risks are estimated. The project is carried out by the consortium Dutch COVID & Thrombosis Coalition. All UMCs and Sanquin participate in this. In addition, there is collaboration with several general hospitals. The research is partly funded by the Trombose Foundation Netherlands.",2020,2021,Erasmus MC,669720,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C09412,1.043E+13,Collaborate against Corona with Intensive Care Data,"Project description Treatment in intensive care appears to be necessary for many COVID-19 patients. It is of great importance to gain more insight into the disease course of intensive care patients with COVID-19 and the factors that influence it. This can give direction to the treatment of future patients, help in the choice of who should and should not be treated in intensive care and contribute to future capacity planning. Research The project investigates which combination of treatments and properties of which individual intensive care patients with COVID-19 leads to the best outcomes. This is done by means of machine learning, an important form of artificial intelligence, which is applied to large amounts of data from intensive care patients with COVID-19 from some 50 collaborating hospitals. The project is supported by the Dutch Intensive Care Association and the National Intensive Care Evaluation Foundation.",2020,2022,Amsterdam UMC - locatie VUmc,393348.88,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2020 +C09450,109136-004,Documenting household food systems in seven zones of West Africa in the context of the COVID-19 pandemic and the distancing measures put in place by the authorities.,,2020,-99,SOCODEVI,75330.75,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa,,,,Canada,Cote d'Ivoire | Mali | Ghana | Senegal,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09451,109097-002,Generating evidence on the effects of COVID-19 and drawing lessons on the resilience of the informal food economy in the great Dakar metropolis,,2020,-99,Consortium pour la Recherche Économique et Sociale (CRES),75000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Senegal,Senegal,"Secondary impacts of disease, response & control measures",Economic impacts, +C09452,108974-002,Documenting the impact of COVID-19 on local food production and informal food markets in Nigeria with Niger Delta region as case study,,2020,-99,Centre for Population and Environment Development (CPED),74475,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Nigeria,Nigeria,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09453,108855-003,Analysing the impacts of COVID-19 pandemic on food production and supply systems in Kenya and Uganda -,,2020,-99,National Agricultural Research Organization (NARO),73650,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Uganda,Kenya | Uganda,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09454,108424-002,"Food security in urban Johannesburg during the COVID-19 lockdown: food parcels, social grants, and local food economies",,2020,-99,PRICELESS South Africa,66750,Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,South Africa,South Africa,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09455,108867-002,"Assessing gender sensitive policy implications of COVID-19 on youth agri-preneurship resilience in the poultry, horticulture and fish (phf) agribusiness value chains",,2020,-99,United States International University Africa (USIU),74925,Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Gender,,,Kenya,Kenya,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09456,108657-002,Documenting the impact of COVID-19 on food systems and trade between Tanzania and the East African Community (EAC) partner states,,2020,-99,Economic and Social Research Foundation (ESRF),75000,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Tanzania,Tanzania,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09457,109204-002,Understanding the cascading impacts of COVID-19 and how it is re-shaping staple food value chains in Zimbabwe,,2020,-99,Agricultural Model Intercomparison and Improvement Project (AgMIP),73575,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa,,,,United States of America,Zimbabwe | Ghana | Senegal,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09458,108865-002,Assessing the resilience of the fish value chain to the COVID-19 pandemic in Malawi,,2020,-99,University of Malawi,76500,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Malawi,Malawi,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09459,108756-002,Assessing the effect of coronavirus response measures on food and nutrition security in Semi-arid Kenya,,2020,-99,Kenya Agricultural and Livestock Research Organization (KALRO),75000,Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Kenya,Kenya,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09460,109577,Response to COVID-19 through social protection and the strengthening of local food systems: The case of the Niayes in Senegal_COVID19-AFS,,2020,-99,IPAR,489450,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Senegal,Senegal,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C09461,109578,Impacts of Government's COVID-19 responses on food systems and livelihoods in the Sahel_COVID19-AFS,,2020,-99,West and Central African Council for Agricultural Research and Development,561450,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Senegal,Gambia | Ghana | Nigeria | Burkina Faso | Cabo Verde | Mali | Niger | Senegal,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09462,109579,Project to support the definition and implementation of relevant and sustainable measures in response to the effects of COVID-19 in the livestock sector in West and Central Africa (WCA) _COVID19-AFS,,2020,-99,APESS,559350,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Nigeria | Burkina Faso | Cameroon | Chad | Guinea-Bissau | Mali | Niger | Senegal,Nigeria | Burkina Faso | Cameroon | Chad | Guinea-Bissau | Mali | Niger | Senegal,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09463,109580,The Impacts of Covid-19 Responses on the Political Economy of African Food Systems_COVID19-AFS,,2020,-99,"University of Western Cape (Institute for Poverty, Land and Agrarian Studies (PLAAS))",544200,Other | Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,South Africa,Ghana | Tanzania,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09464,109581,"COVID 19 crisis and impact on the pillars of Food Security (SA) and opportunities for reconfiguring unequal gender relations, in Burkina Faso and Senegal: Research project_COVID19-AFS",,2020,-99,CECI,560014.5,Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa,Gender,,,Canada,Burkina Faso | Senegal,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09465,109548,Broad-spectrum antiviral nasal sprays to prevent infection by SARS-CoV2 and seasonal respiratory viruses in patients and healthcare providers,"In March 2020, the World Health Organization declared a pandemic due to the emergence of a novel coronavirus (SARS-CoV2) which causes COVID-19, a potentially lethal respiratory infection. There are currently no antiviral agents to prevent or treat SARS-CoV2 infections. This project proposes the optimization and prototype development of a broad spectrum antiviral pharmaceutical preparation (RespVirex) to protect healthcare workers and high-risk patients from SARS-CoV2 and dozens of other seasonal and pandemic viruses. The team aims to deliver RespVirex by nasal spray and nebulized aerosol. A nasal spray can be dosed conveniently by healthcare workers as needed during respiratory virus seasons or a pandemic. RespVirex can also be inhaled by nebulizer to treat the lower respiratory tract. The pharmaceutical formulation of the nasal spray and nebulized aerosol will be developed in Canada, while its ability to inhibit SARS-CoV2 and other respiratory viruses will be evaluated at the Institut Pasteur in Dakar, Senegal.",2020,-99,University of Alberta,496860,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Senegal,Senegal,"Therapeutics research, development and implementation",, +C09466,SARSCov2-2-20-002,Consortium for Rapid COVID-19 Drug Development in Africa,"Candidate vaccines, diagnostics and therapeutics",2021,-99,Rhodes University,200000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,South Africa,South Africa,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics | Pre-clinical studies | Pre-clinical studies, +C09467,SARSCov2-2-20-004,Compliance with Covid-19 prevention measures: a behavioural economics approach,Infection prevention and control including health care protection,2021,-99,University of Pretoria,74456,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,South Africa,South Africa,"Infection prevention and control | Policies for public health, disease control & community resilience",Approaches to public health interventions, +C09468,SARSCov2-3-20-002,Impact of co-infections and host genetics on susceptibility to SARS-CoV-2 infection and COVID-19 disease severity in well-characterised study cohorts in Uganda (CoHost),Epidemiological studies,2021,-99,Uganda Virus Research Institute,199945.28,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Uganda,Uganda,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C09469,SARSCov2-3-20-006,"Lactoferrin, ovotransferrin and lysozyme (egg white and milk) as an intervention to prevent severe COVID-19","Candidate vaccines, diagnostics and therapeutics",2021,-99,University of KwaZulu Natal,200000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,South Africa,South Africa,Clinical characterisation and management,"Supportive care, processes of care and management", +C09470,SARSCov2-4-20-002,Influence of pre-existing cytokine profile on the outcome of exposure to COVID-19,Epidemiological studies,2021,-99,KEMRI-Wellcome Trust Research Programme,199727,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Kenya,Kenya,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility, +C09471,SARSCov2-4-20-004,Validation of serological assays to enhance COVID-19 surveillance in Ghana,Epidemiological studies,2021,-99,"Noguchi Memorial Institute for Medical Research, University of Ghana",198912.6,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Ghana,Ghana,Epidemiological studies,Disease transmission dynamics, +C09472,SARSCov2-4-20-005,PAMGENe-COVID-19; Dynamics of SARS-CoV-2 and Plasmodium species co-transmission and genetic variation across a gradient of malaria endemic areas in Africa,"Candidate vaccines, diagnostics and therapeutics",2021,-99,MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine,199610,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Gambia,Gambia,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics", +C09473,SARSCov2-4-20-006,Respiratory Coinfections and Microbiome in COVID-19: Prevalence & Implications,Epidemiological studies,2021,-99,Uganda Virus Research Institute,199990,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Uganda,Uganda,Epidemiological studies,Disease surveillance & mapping, +C09474,SARSCov2-4-20-008,"Examining key emerging ethical issues in the planning, review and implementation of COVID19 research in Africa, and the preparedness and responsiveness of research review authorities",Ethical considerations for research,2021,-99,KEMRI-Wellcome Trust Research Programme,196607,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Kenya,Kenya,Research to inform ethical issues,Research to inform ethical issues in Research, +C09475,SARSCov2-4-20-010,PlexiCov: Covid 19 antigen Point of Care Testing; Development and Implementation Research,"Candidate vaccines, diagnostics and therapeutics",2021,-99,Mount Kenya University,199950,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Kenya,Kenya,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09476,SARSCov2-4-20-011,Assessing host and viral factors for Covid-19 disease outcomes in Tanzania,Epidemiological studies,2021,-99,Centre Suisse de Recherches Scientifiques en Côte d'Ivoire,200000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Cote d'Ivoire,Cote d'Ivoire,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C09477,SARSCov2-4-20-022,Enhancing Genomics Characterization and Surveillance of SARS-CoV-2 in Nigeria.,"Candidate vaccines, diagnostics and therapeutics",2021,-99,Redeemer's University,200000,Unspecified,Not applicable,Not Applicable,Not applicable,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,African Academy of Sciences (AAS ),Kenya,Africa,Africa,Africa,,,,Nigeria,Nigeria,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C09493,AH/V013947/1,UK Ethics Accelerator: Coordinating and Mobilising Ethics Research Excellence to Inform Key Challenges in a Pandemic Crisis,"The COVID-19 crisis demands that policy-makers, researchers, health and social care workers, and members of the public address unprecedented ethical dilemmas on a daily basis. Resolving these is hard, and it is risky. The complexity and speed of ethical challenges are leading to harms-some inevitable, some avoidable-on a significant scale. The main aim of the Ethics Accelerator (EA) is to harness and mobilise existing UK ethics research expertise to bear on these multiple, ongoing ethical challenges. The EA will rapidly provide evidence, guidance and critical analysis to decision- makers, helping to improve decision-making over the evolving pandemic response. A second aim is to enable systematic public deliberation around key ethical challenges. A third aim is to identify strategies to embed ethics at the core of future epidemic preparedness. The EA will leverage and promote a broad network of UK and international researchers to create flexible Taskforces that deliver rapid guidance and responsive advice to leadership in government, science, medicine, and public health. It will establish virtual fora for public discussion, deliberation and information about arising ethical challenges. In coordinating and focusing existing national investments in ethics research, the EA adds significant value and scales up the potential impacts of ethics research in science, medicine, policy and society. Primary outputs will be rapid research reviews; policy guidance; commissioned research; a broad peer review body; and stakeholder engagements. Main outcomes will be decision-making that is informed by ethics expertise, and is more transparent and accountable, thereby improving public trust.",2020,2022,University of Oxford,1534441.05,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues | Research on Capacity Strengthening,Research to inform ethical issues in Research | Cross-cutting,2020 +C09494,ES/V006029/1,Co-producing knowledge about the impacts of emergencies/pandemics: developing remote participatory visual methods using smartphones,"The goal of this project is to respond to the challenges of methodological co-production and participatory action research - which are almost always conducted in person face-to-face - that arise during emergencies by developing an innovative remote participatory visual method using smartphones. In collaboration with migrant women in Colombia and a Londonbased film company, we will co-develop and test a novel and pioneering remote participatory visual method for coproduction researchers by applying participatory filming remotely to investigate the impact of the COVID-19 pandemic on women's new lived realities of urban life. The whole research process, from development to dissemination, will be conducted online. During emergencies, such as the COVID-19 pandemic, face-to-face research becomes impossible through travel and social contact restrictions. Many researchers have been stalled immediately prior to, or during, data collection, but the need to work with research participants remains. The same can occur in contexts of climate emergencies, disasters, conflict affected areas or in situations where there is not enough funding available for international travel. This is particularly challenging in transnational research and where collaborative research methodologies conducted with marginalised communities in times of such crisis become even more pressing. A remote participatory visual methodology provides a solution to continue or initiate participatory work, whilst ensuring that co-production and impact research still holds the potential to create social change and transformation of past, current and evolving issues. One of the most promising solutions to be able to co-produce knowledge without face-to-face in-person contact is the use of smartphones to collect and share audio, visual and written data. The increased use of smartphones worldwide provides an opportunity for researchers to connect to participants transnationally remotely and for participants to still being able to express their voice. A remote participatory visual methodology may thus offer deep insights during emergencies, coproduced with participants to include those whose voices are traditionally unheard, while working towards the equalisation of power-relationships during the research process. To successfully develop a pioneering remote participatory visual method in this project, an interdisciplinary research team in the UK and Colombia consisting of Geography, Sociology, International Development, Filmmaking and Education and Human Rights scholars and a London-based film company will explore and test the methodological, ethical and technical challenges and possibilities of the use of smartphones for remote participant recruitment and participatory visual data collection. In collaboration with migrant women in Colombia, we will produce four filming and evaluation cycles, during which we will train researchers and participants in filming techniques, while at the same time collecting filmed material to produce short films of how the pandemic impacts the women's negotiation of their gendered right to the city in Medellin and Bogotá. Methodologically, the research will develop, pilot and evaluate a novel remote participatory visual method that can shift the co-production research landscape and make this form of research more accessible in contexts that have been excluded because of lack of face-to-face access to participants. The project will produce training materials for social science researchers. Substantively, the research project will contribute co-produced knowledge about women's gendered right to the city, including the voices of vulnerable women who are frequently absent from contemporaneous commentaries of emergencies and disasters, especially in situations where face-to-face contact is impossible or undesirable.",2020,-99,London School of Economics and Political Science,227857.05,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Internally Displaced and Migrants | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe,Gender,,,United Kingdom,United Kingdom | Colombia,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09495,ES/W000482/1,Motivational interviewing for contact tracing: developing co-produced training to improve practice,"Contact tracing is currently a national priority, due to its centrality to infection control; low rates of self-isolation compliance (Smith et al., 2020); and regional and centralised initiatives (Iacobucci, 2020; Williams, 2020). Recently, the government proposed fining individuals for not adhering to requests to self-isolate (Hope, 2020). However, this appears to contravene the widely-accepted position, that intrinsic motivation promotes behavioural change (Marmot, 2015; Rollnick, Butler, Kinnersley, Gregory, & Mash, 2010). Motivational interviewing (MI) is a collaborative conversational style for promoting motivation and commitment to behavioural changer (Miller & Rollnick, 2013). Its potential role in improving social distancing and other COVID-19 related safety precautions has already been highlighted (Ross, Zerden, Ruth, Zelnick, & Cederbaum, 2020); as have its benefits for contact tracing within sexual health (Op de Coul, Spijker, van Aar, van Weert, & de Bruin, 2013). MI is effective for working with clients who feel ambivalent about change, making it potentially ideal as a way of talking to individuals testing positive with the COVID-19 virus, who may have conflicting feelings about self-isolation. This exploratory study seeks to consider the feasibility of developing and delivering brief, accessible MI training for contact tracers. The project would involve the co-production, delivery and evaluation of the training. It is anticipated that, in line with previous research (Op de Coul et al. , 2013), the training would improve the skills and self-efficacy of contact tracers, with this also impacting wellbeing. Future research could then seek to assess its potential impact on public engagement with self-isolation, following contact tracing.",2020,-99,University of Manchester,31823.55,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Community engagement | Individual level capacity strengthening, +C09496,ES/W000474/1,Vulnerable Children in a Hostile Environment: The Legal and Social Impacts of Covid-19 on Young Unaccompanied Asylum-Seekers in England,"The proposed research will provide the first in-depth empirical analysis of the legal and welfare effects of Covid-19 on unaccompanied asylum seeking children in the UK (UASCs). It will evidence empirically how UASCs and their legal, welfare and civil society representatives are responding to the delays and disruption in front line services and suggest concrete legal, policy and practice proposals to ensure their rights and welfare are upheld. The project is methodologically innovative in that it will involve co-researching with a team of young UASCs who will facilitate engagement with up to 80 other UASCs. This will be complemented by data from online practitioner surveys and interviews, FoI requests from the Home Office and Local Authorities, and a detailed review of the relevant case law, statutory and policy guidance.",2020,-99,University of Liverpool,386606.25,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C09497,ES/V017551/1,Small and medium enterprises (SMEs) digital footprints and its ethical implications during COVID-19 outbreak and beyond,"This project focuses on SMEs who have been facing challenges regarding the rapid increased usage of digital tools (e-mails, cloud, big data) especially after the COVID-19 outbreak. Digitisation of the business environment creates digital footprints (electronic information each employee or organisation creates, transfers or receives in the form of emails, document-sharing, calls or chats). Digital footprints blur the boundaries between the individuals and organisations, which creates various risks in transparency, equality and inclusion. In the World Bank Report (2016), access to the internet was estimated to have the potential to generate over $2.2 trillion in additional GDP and more than 140 million new jobs worldwide. With the outbreak of the COVID-19 pandemic, these figures will surely increase, where digitalisation, along with its challenges, is expected to be in the heart of our business and social lives. In April 2020, according to the latest research by the Office of National Statistics (ONS, 2020), 46.6% of employees did some work at home, with 86% of these doing so as a result of the COVID-19 pandemic. The proposed project focuses on developing an analytical framework that can help SMEs to better understand their digital footprints and their ethical implications. Through qualitative methods including netnography and in-depth interviews, the project plans to develop insights both at organisational and individual levels to use digital footprints ethically and safely in creating business and social value. Our potential analytical framework can help shape more definite post-COVID and ""future of work"" scenarios.",2020,-99,Brunel University London,175354.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09498,ES/W000156/1,Learning from the impact of and recovery from COVID-19 within prisons: the effect of COVID-19 management and the environment on wellbeing and harm.,"COVID-19 is a particular challenge within the prison setting given the vulnerable nature of the population (in terms of emotional dysregulation, mental health difficulties, rates of suicide, self harm and violence); the characteristics of individuals (e.g. high rates of BAME) and the physical conditions (e.g. difficulties of introducing social distancing without the potential for exclusion). This research uses a carefully selected subgroup (those accessing the Offender Personality Disorder Pathway across 34 prison sites) as a case study from which to generalise across the prison context. The combination of quantitative methods (using linear mixed modelling to examine extensive and existing data) and qualitative research (based on interviews with a purposive sample) will enable this research to determine a) the impacts of prison restrictions implemented in response to COVID-19 and the subsequent easing of these on psychological and behavioral outcomes and b) to identify key factors associated with differences in response to restrictions / easing. Understanding and learning from the impact of COVID-19 and the resultant management responses within prisons is essential in order to identify how to build resilience in readiness for further restrictive measures which may be needed during subsequent 'outbreak waves'. Such findings will also have long term implications with regard to effective practices in the context of a return to standard operating status which might enhance the existing prison regime. Finally, this research will also allow us to examine whether certain groups (e.g. ethnic groups) experience a disproportionate impact in prison, as occurs in the wider/non-prison community.",2020,-99,Swansea University,342846,Human Populations,Unspecified,Unspecified,Unspecified,Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C09499,ES/V017543/1,Occupational changes and skill mismatch following Covid-19: implications for graduates in the UK,"This study investigates how the distribution of workers across occupations has changed during the Covid-pandemic, and how such changes have affected the match between workers' education and the requirements of a particular occupation. This skill mismatch is likely to have increased during the pandemic, with an increase in the associated costs of lower earnings, lower job satisfaction and lower productivity. This study aims to: (1) evaluate the extent of occupational shifts; (2) estimate the impact of the pandemic on the skill-mismatch, both nationally and regionally; (3) analyse the uptake of training during the crisis and whether this reduces the skill mismatch. Analysing occupational shifts will provide vital understanding of how labour market opportunities are changing. Shifts in occupations could lead to a loss of human capital, if workers made redundant cannot find an alternative occupation matching their qualification. This can have long-term effects on their future career and on productivity. Training may offset this situation by allowing workers either to remain in their current occupation or to find a match where their skills are going to be valued. Although undoubtedly the repercussions of the pandemic affect all types of workers, we focus on graduates and younger workers since they are facing very uncertain job prospects and they are more likely to be at risk. They are also more occupationally and geographically mobile. Work by Vecchi (Co-I) and the ONS also shows that the incidence of overeducation is higher among graduates, which further justifies focusing on this group of workers.",2021,2022,University of Kent,66988.35,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C09500,BB/V019864/1,Cell Stress and risk of COVID-19,"It is now well established that certain pre-existing conditions (including cancer, hypertension, obesity, lung disease, and diabetes) greatly increase the risk of severe disease and death from COVID-19. However, the causal link between these co-morbidities and COVID-19 severity remains poorly understood. Most proposed explanations have focused on these conditions causing chronic organ dysfunction and therefore limited physiological reserve. Here we propose an alternative hypothesis: that chronic cellular endoplasmic reticulum (ER) stress, resulting from these diseases, pre-disposes patients to SARS-CoV-2 infection and heightened viral replication. All the aforementioned co-morbidities are characterised by chronic, elevated ER stress. In normal cells, when ER stress is induced by external stimuli, ER proteins are upregulated to allow cells to halt translation, resolve protein misfolding and restore cellular homeostasis. However, this balance is perturbed where cells under long term, chronic ER stress. To protect cells from apoptosis, key ER stress response proteins remain upregulated and, as we have demonstrated in cancers, the cells become ""addicted"" to these proteins for their survival. We have shown, by both immunoprecipitation and immunofluorescence, that the nucleocapsid (N) protein of SARS-CoV-2 binds to cellular ER stress proteins. We have also shown that cells increase their expression of these proteins following infection by SARS-CoV-2. We therefore aim to determine the role played by ER stress in the viral life cycle, specifically in viral replication. We propose that in diseases involving chronic ER stress, SARS-CoV-2 hijacks the cellular dependency on the ER stress response to promote its own replication and ensure the preferential translation of viral proteins. We hypothesise that chronic medical conditions associated with ER stress have COVID-19 predisposition because they have higher cellular and circulating levels of ER stress proteins, which facilitate viral replication and worse outcome. Furthermore, this may implicate circulating ER stress proteins as potential biomarkers for COVID-19 risk, even in the absence of a diagnosed condition. We will determine if pre-existing ER stress allows increased replication of SARS-CoV-2 and, by depleting key ER proteins, will determine if they play a mechanistic role in the viral replication cycle. The second aim of this project is to determine whether the release of viral proteins and RNA into exosomes can promote the spread of SARS-CoV-2 between cells. Several viruses are known to utilise this mechanism as it can shield viral components from recognition by the immune system, and can prime cells for more efficient infection by virions. We have shown previously that certain ER proteins are released within exosomes upon exposure to stress. As we have also demonstrated binding of these proteins to SARS-CoV-2 N protein, there is a strong likelihood that N protein and viral RNA are also packaged into the exosomes of infected cells. We will determine (1) if viral components are packaged into exosomes, (2) if ER proteins are required for this process and (3) whether these viral exosomes promote the spread of SARS-CoV-2 between cells.",2020,2022,University of Oxford,80908.2,Viruses | Other,Not applicable,Not Applicable,Not applicable,Individuals with multimorbidity | Other,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C09501,BB/V019848/1,"Identifying binding partners, biological substrates and antisense oligonucleotides regulating expression of short and long ACE2.","ACE2 is the main viral entry point for SARS-CoV-2. We and others have recently demonstrated that two forms of ACE2, short and long, are expressed in airway epithelial cells, and that expression of these is under the control of independent promoters, with short ACE2 being strongly induced by IFN. Both are upregulated in response to rhinovirus infection but not SARS-CoV-2 infection. Short ACE2 lacks the high affinity binding residues for SARS-CoV-2 spike binding, suggesting that it is not capable of SARS-CoV-2 binding. Preliminary work suggests that short ACE2 is less stable than long ACE2. Short ACE2 has a transmembrane domain but no signal peptide, and it remains unclear whether short ACE2 is located in the membrane and the mechanism of transport of ACE2. As a recently discovered molecule, little is understood about the physiological function of short ACE2 and its role in SARS-CoV-2 infectivity. In this project we aim to identify the binding partners and biological substrates of short and long ACE2 and investigate whether modulation of expression of short and long ACE2 with antisense olignucleotides can modify SARS-CoV-2 infectivity in cell models of respiratory epithelium.",2020,2021,University of Southampton,206194.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C09502,BB/V01854X/1,Airway Epithelial-Myeloid cell crosstalk as a key mechanism in the pathogenesis of COVID-19,"Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the cause of COVID-19, causes mild to severe respiratory illness exacerbated by aging and comorbidities. Patients can develop acute respiratory distress syndrome (ARDS) or multi-organ injuries associated with elevated levels of pro-inflammatory cytokines, including IL-6 and TNF-alpha, alongside minimal amounts of type I IFNs. Reduced Type I IFN production is likely caused by viral antagonism of innate immune responses hampering induction of a robust anti-viral state in the airway epithelium and surrounding tissues facilitating increased viral titres. We hypothesise that crosstalk between infected lung epithelial cells, targeted by SARS-CoV-2 but poor cytokine producers, and myeloid cells, not susceptible to SARS-CoV-2 infection but major producers of cytokines, will contribute to the cytokine imbalance and storm characteristic of COVID-19. The main objective of this study is to establish the role of monocytes/macrophages as amplifiers of inflammatory responses during SARS-CoV-2 infection including evaluating the effect of existing or new drugs. Towards this aim we will (1) Characterise SARS-CoV-2 infection in differentiated primary human airway epithelial cells, both nasal and bronchial cells including; viral growth, cytotoxicity and cytokine production. (2) Determine if crosstalk between airway epithelial cells and monocytes/macrophages influences SARS-CoV-2 infection and can be targeted by existing and new drugs. We will use individual and co-cultures of airway epithelial cells and monocytes/macrophage to (i) investigate changes in cytokine production, (ii) determine if SARS-CoV-2 infection of epithelial cells can be augmented by the presence of myeloid cells, (iii) if monocytes/macrophages can become targets for SARS-CoV-2 and (iv) the effect of drugs on each aspect.",2020,2022,University of Nottingham,334540.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C09503,MR/V03958X/1,Translating potent SARS-Cov2 neutralising nanobodies from the lab to the clinic,"There is currently no cure or vaccine for Covid-19, passive immunotherapy however may prevent halt or ameliorate disease. We have identified multiple single domain antibodies (nanobodies) that neutralise live SARS-CoV-2 virus with picomolar efficacy in vitro. Working with Public Health England, we will test the efficacy of these neutralising nanobodies in a hamster model of mild to moderate disease with the prospect a novel nanobody-based medicine being developed for the treatment for Covid19. Nanobodies are so called because they are single domain (in fact heavy chain) containing the variable region and they derive from camelids. A nanobody is around 120 residues in length (~ 15 kD) and can access epitopes not normally seen by the human immune system. The variable gene sequences of camelids are similar to human and it has been proposed that nanobodies are less likely to be immunogenic than antibodies of other species. The relatively small size and stability of nanobodies gives them a unique advantage over human antibodies, which must be injected or given IV, nanobodies can be given as direct aerosolised delivery to the patient. Such an easy to administer and cheap therapy would transform the outlook for covid19. By the end of the project we aim to have established whether a neutralising nanobody to SARSCov2 is effective in an animal model of Covid19 and in particular whether a therapeutic / prophylactic dose can be delivered by nasal administration. In parallel the potential of candidate nanobodies to elicit virus escape mutants will be assessed.",2020,2021,The Rosalind Franklin Institute,270530.55,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C09504,EP/V054236/1,RAMP VIS: Making Visual Analytics an Integral Part of the Technological Infrastructure for Combating COVID-19,"Computational modelling of the COVID-19 pandemic has been playing a significant role in the UK's effort to combat COVID-19. Across the country, there are about 100 research teams working on different models, and several dozens have provided simulation, estimation, and prediction to inform the governmental decisions in the four home nations. One noticeable oversight is the under-utilisation of visualization and visual analytics technology in supporting the scientific workflows for model development, which typically consists of a set of iterative processes, such as (a) hypothesis formulation and causality analysis; (b) model development, testing, validation, and comparison; (c) model deployment, monitoring, and improvement; and (d) scientific and public dissemination. Because visualization is widely mistaken only for information or knowledge dissemination, the technology is commonly underused in all other stages of a modelling workflow. Ideally, modelling scientists and epidemiologists could have a quick glance of dynamic data anytime there is a need (cf. stock brokers observing stock market data), access effective overviews of spatiotemporal patterns of the disease development and control (cf., meteorologists observing satellite images, contour maps, etc.), be provided with external memorization of data to stimulate hypotheses and contemplate various decisions (cf. a general pacing around in a war room in front of many maps), and receive advice from an ensemble of analytical algorithms and visualizations about similarity, anomalies, clusters, correlation, causality, and association hidden in the data (cf. a CEO consulting specialists). Ideally, there is a visual analytics infrastructure, as a ""standing capacity"" (Secretary of State), that can support many modelling teams performing daily observational, analytical, and model-developmental tasks. The proposed VA technical and knowledge infrastructures are essential for combating COVID-19 pandemic, as many epidemiologists are preparing for COVID-10 to be a threat for some time. With the recent introduction of localised control measures, it indicates an additional need for localised VA supports for many local scientists and healthcare professionals. When vaccination starts, there is a need for monitoring and modelling the effectiveness of different vaccines used in different regions. Such a nationwide need can be cost-effectively delivered by the VA technical and knowledge infrastructures.",2020,2021,University of Oxford,581170.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +C09505,EP/V053922/1,"The CIVIC Project: A Sustainable Platform for COVID-19 syndromic-surveillance via Health, Deprivation and Mass Loyalty-Card Datasets","In light of ongoing COVID-19 infections, and approaching second waves, there is urgent need to: N1. Vastly improve estimation of UK-wide unrecorded cases. N2. Identify key antecedents of COVID in mass, UK-wide behavioural data, that can power urgently needed early-warning systems at scale; sustainably; and without reliance on self-reporting apps. N3. Model impact to hidden, vulnerable communities (e.g. food poverty, BAME), to help long-term intervention strategies. CIVIC is ideally placed to address these needs via unparalleled granularity of access to mass behavioural data; A unique partnership: private-sector data-providers (e.g. Boots, OLIO, Fareshare), academic expertise (Epidemiology, Behavioural Science, AI/Statistics), and public-sector impact partners (ONS, JBC, NHS-X) building an unprecedented platform via 3 interlinked work-packages: WP1. Partnership with Boots/NHS to generate first-ever, sustainable models of untested COVID-19 cases through interrogation of mass, line-item health/pharmacy transaction data (validated against 111-call-data). WP2. Identification of behavioural and clinical antecedents of COVID-19 outbreak; processing mass retail loyalty-card/point-of-sale logs via AI/machine-learning techniques, generating near-future forecasts, underpinning early-warning systems. WP3. Modelling of hidden social/economic impacts to key vulnerable communities, identified in actual behavioural patterns not simple demographic projections. Each WP has 2 stages. Stage-1 focuses on strictly-anonymized, aggregated data derived from >1.5 billion transactional records, providing crucial deliverables and revolutionizing insights for each of the UK's 32,884 neighbourhoods (LSOAs) within just 4 months. Stage-2 increases fidelity, via individual-level modelling via a ground-breaking ""Data Donation"" framework.",2020,2021,University of Nottingham,315852.75,Other,Asian | Black,Not Applicable,Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Economic impacts,2020 +C09506,EP/V052462/1,'COVAIR': Is SARS-CoV-2 airborne and does it interact with particle pollutants?,"Aerosol dispersion and environmental spread of SARS-CoV2 virus apart from direct inhalation of large droplets from a cough or exhaled breath of an infected person remains a high possibility. SARS-CoV2 virus has been collected from the air of hospitals with COVID-19 patients and the presence of the virus on particulate matter has been reported in Northern Italy. We wish to develop diagnostic tools and predictive sensing to detect SARS-CoV2 in crowded urban environments in order to address whether the airborne amounts are high enough to cause a respiratory infection and whether pollution particles can carry live virus that is directly inhaled into the lungs. We will determine whether SARS-CoV2 can be detected as active virus in the air of hospitals with COVID-19 patients, and if so, use a similar technique to measure the virus in crowded spaces such as in underground train platforms, central station concourse, shopping malls and busy roadside. We will use and validate different methods of collecting particles from experience obtained from our EPSRC-funded INHALE project. Particles will be collected onto filters, and virus and virus-particulate interactions determined by RT-PCR (RNA-based), culturing on Vero E6 cells and airway epithelial cells, and using state-of-the -art electron microscopy. We will model this mode of transmission into the lungs by studying airflows and pollutant levels, and as a measure of this infection in the population. This method can be potentially considered as a surveillance assay of crowded public areas for SARS-CoV2 with ~ 2,000 new infections currently reported daily.",,,Imperial College London,696551.4,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2021 +C09507,ST/V006126/1,"Open Epidemiology for pandemic modelling: a transparent, traceable, reusable, open source pipeline for reproducible science","Historically, models used to support advice to government have not been publicly available, at least not readily, prior to publication. Technological advances and the growth of open source and reproducible science mean this is no longer tenable. Although current models feeding into UK policy are publicly available, they still lack the transparent and readily traceable chain of evidence connecting data and assumptions with model outputs that allows them to be readily independently assessed. Our Data Pipeline supports the implementation of COVID-19 epidemiological models that we, the Scottish COVID-19 Response Consortium (SCRC), have developed using volunteer resources within the RAMP initiative, to create new, complementary models. The Data Pipeline fulfils a critical role in our assessment of fitness for purpose for the models in providing policy advice, by managing and documenting a chain of trust that connects the primary data, analyses, and published and unpublished literature on COVID-19 to model outputs, documenting provenance of the conclusions being reached. The software interfaces we develop will be powerful, generic tools that will be useful to any policy-oriented modelling community.",2020,2022,University of Glasgow,679847.85,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Epidemiological studies,,2021 +C09508,3P20GM104417-07S1,Center for American Indian and Rural Health Equity,"Project SummaryThe COVID-19 pandemic has disproportionately affected American Indian (AI) and Latino communities, andthese groups also have increased risk of poor prognosis due to high rates of chronic disease such as diabetes,cardiovascular disease, and cancer. In the northwestern United States, AI and Latino communities alreadyface significant disparities in health care access, which have been further exacerbated by the COVID-19pandemic. In the proposed study, Protecting Our Community: A Pragmatic Randomized Trial of Home-BasedCOVID Testing with American Indian and Latino Communities, we will leverage our long-term community-based participatory research partnerships to test the hypothesis that home-based testing will be feasible,impactful, and better-accepted using active delivery of test kits by trusted community health educators in twovulnerable, high-risk rural communities. Our two long-term partner communities are the Flathead IndianReservation of the Confederated Salish and Kootenai Tribes in Montana, and the Yakima Valley ofWashington, a large Latino community. We will determine the cultural, social, behavioral, and economicbarriers to home-based SARS-CoV-2 testing; culturally adapt and enhance home-testing educational materialsand create home-testing instructional graphics and YouTube videos; conduct a 2-arm pragmatic randomizedtrial of active (delivered by community health educator) vs. passive (mailed) home-based testing kits (n =200/community) for testing completion; and create model community-driven testing protocols that can havesignificant impact for increasing home-based testing uptake among AI and Latino communities nationally. Thiswork will enable underserved AI and Latino communities to take full advantage of the coming wave of rapidpoint-of-care home tests and decrease the significant impact of COVID-19 in their communities.",2020,2024,Montana State University - Bozeman,1115953,Human Populations,Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Policies for public health, disease control & community resilience","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Community engagement",2020 +C09509,3R01ES028615-06S1,"Investigating the effectiveness of COVID-19 testing choices, community engagement, and culturally-embedded mHealth literacy delivery in a medically-underserved, community-based sample","Since the first U.S. cases were identified in Washington on January 20th and soon thereafter in Chicagoon January 24th, COVID-19 has rapidly emerged as the most prevalent and deadly respiratory infection withinthe State of Illinois, with 220,178 total confirmed cases and 7,880 (3.6%) deaths. The UIC Hospital and HealthCare System (UI Health), in collaboration with its 14 partnering Federally Qualified Mile Square Heath Centerpractice sites (FQHCs) (where this project will be implemented), saw over 4,000 of these cases between Marchand June, 2020 (6), noting the disproportionately higher rates if COVID-19 in Latinx people (47.1% with 32.7%of deaths) and in people identifying as African American or Black (28.9% with 43.1% of deaths). Of 48,111 casesreported in Cook County alone, 7,231 (15.0%) were hospitalized with 2,234 (4.6%) in an intensive care unit.These COVID-19-related morbidity and mortality disparities are accompanied by numerous other healthdisparities. Many of our FQHCs lack the staffing and revenue to test on-site and provide extensive follow-upoutpatient care for the large influxes of symptomatic patients concerned about COVID-19. These challengeshave likely resulted in increased COVID-19-related complications and deaths that might have been preventedwith clearer and more accurate public messaging about COVID-19, wider access to testing, earlier diagnosis,and an increased perception that care is confidential, accessible, and self-driven. This project will employsentinel and community-based epidemiological surveillance and participatory research methods to evaluatewhether a person-centered, rapid COVID-19 testing intervention (at-home swab and send, or on-site point ofcare testing), coupled with a novel mHealth COVID-19 Literacy and Outreach Suite of apps and videos, willserve to increase the acceptance, access, reach, uptake, and impact of COVID-19 testing at UI Health and in the14 FQHC practice sites and their corresponding catchment areas. We will also analyze the social, ethical,economic, and behavioral drivers and consequences of our outreach and testing approaches according to thedegree to which participants contribute to the co-creation of study-related messaging. Finally, we will leverageour existing infrastructures to expand testing uptake and analyze (by PCR) viral load at infection onset/exposure and following onset/exposure to determine viral dynamics and identify individuals at early andlate stages of infection. PhenX measures will be used to test intervention effects on testing and retesting uptake, time-to-diagnosis, COVID-19 knowledge, healthcare access and seeking, disclosure, medical adherence,and practice of home self-isolation, quarantine, and other infection control behaviors. All data acquisition,collection and curation approaches will be informed by the CDCC, including AboutML-informed consentapproaches and with the other RADxUP studies and relevant federal agencies.",2020,2022,University Of Chicago,1609765,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Approaches to public health interventions,2020 +C09510,3P30NR016587-05S1,Reaching Communities through the Design of Information Visualizations (ReDIVis) Toolbox for Return of COVID-19 Results,"The overall goal of Reaching Communities through the Design of Information Visualizations (ReDIVis) Toolboxfor Return of COVID-19 Results (RCR) is to decrease health disparities related to COVID-19 by enablingwidespread use of culturally congruent and health literate infographics to return the results of SARS-CoV-2diagnostic and antibody testing in a manner that supports comprehension of the results, informs decisionmaking, and motivates appropriate behaviors. In collaboration with our community partner, the Association toBenefit Children, we will use a mixed-methods research design to achieve the following specific aims:1. Advance understanding of the factors that influence comprehension and use of the results of SARS-CoV-2 diagnostic and antibody testing in underserved and vulnerable populations.2. Collaborate with underserved and vulnerable populations to design infographics for returning the resultsof SARS-CoV-2 diagnostic and antibody testing in a format that maximizes comprehension, informsdecision making, and motivates action.3. Develop, implement, evaluate, and disseminate the ReDIVis Toolbox for returning the results of SARS-CoV-2 diagnostic and antibody testing.ReDIVis Toolbox-RCR builds upon substantial preliminary work in community engagement, lay-personscience, system development and evaluation, and information visualization as well as existing infrastructure:(a) a research cohort of Latino adults, (b) the Visualization Design Studio of the Precision in Symptom Self-Management Center, and (c) the novel COVIDWATCHER lay-person science platform. Informed by seven publichealth ethics principles, ReDIVis Toolbox-RCR research activities (focus groups, interviews, surveys,participatory design sessions, usability testing) will result in the web-based ReDIVis Toolbox that includes: (a)infographics in English and Spanish for returning SARS-CoV-2 test results; (b) documents to support design,implementation, and evaluation of infographics; and (c) software to enable the creation of tailored culturallycongruent and health literate infographics. Within the defined areas of research interests in NOT-OD-20-119,ReDIVis Toolbox-RCR directly responds to the need for SARS-CoV-2 test results templates and toolkitsdesigned in collaboration with communities and strategies and resources to increase use and utility of testresults. In addition, ReDIVis Toolbox-RCR research activities will advance understanding of the social, ethical,and behavioral implications of how test results are interpreted and used; specifically, how the results influencedecision making and COVID-19 mitigation behaviors (e.g., social distancing, self-isolation, mask wearing, andvaccination, when available). Moreover, we will interact with other RADx-UP grantees to enhance thegeneralizability of the ReDIVis Toolbox.",2020,2022,Columbia University Health Sciences,639012,Human Populations,Other,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health | Innovation,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2020 +C09511,3R21EB026008-02S1,DNA Nanoparticle Vaccine for COVID-19,"PROJECT SUMMARY/ABSTRACTCOVID-19 has emerged from SARS-CoV-2 within the course of several months to spread worldwide as a deadlypandemic, with the number of deaths approaching one-half million worldwide. While over one hundred vaccines are currently in development, and several already in human clinical trials, most of these early candidates consist of messenger RNA or DNA formulations used to transiently express SARS-CoV-2 subunit proteins, which maynot elicit sufficiently neutralizing, long-term antibody response. Strategies to enhance antigenicity, antibodyaffinity maturation, and memory induction in response to subunit vaccines are of broad relevance for the designof effective vaccines against infectious diseases such as COVID-19, and may be particularly important toneutralize the SARS-CoV-2 pathogen. One approach to enhance the efficacy of subunit vaccines is to formulateantigens in a multivalent, nanoparticulate form, which promotes several aspects of humoral immunity, mostnotably crosslinking of B cell receptors (BCRs). This approach has been exploited both in licensed vaccines(e.g., the HPV and HBV vaccines), and in a great variety of vaccines in preclinical and clinical development. Inthis project, we use the unique technology of scaffolded DNA origami to engineer virus-like nanoparticles on the10-100 nanometer scale that offer the ability to conjugate controlled copy numbers of SARS-CoV-2 antigens atcontrolled inter-antigen spacings. We test the relative importance of copy number, spacing, and virus-likenanoparticle size on B cell activation in vitro. Optimal constructs identified using B cell activation assays in vitrowill subsequently be used to characterize T-cell and B-cell response in vivo using mouse models. Successfulvaccine constructs identified from in vivo studies will be shared with commercial partners to facilitate follow-ontoxicity, safety, and efficacy studies in higher animal models including non-human primates. Our results will offera novel subunit vaccine formulation that may be generalized to other SARS-CoV variants including SARS-CoV-1 through heterovalent protein antigen presentation, as a generalized vaccine platform to avoid futurecoronavirus-induced pandemics.",2020,2021,Massachusetts Institute Of Technology,370098,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +C09512,3RF1AG041200-06S1,Administrative Supplement Request to Lifespan Cardiovascular Risk Exposures and Alzheimer-related Brain Health,"Sudden changes in cardiovascular (CV) risk factors, especially diet quality, physical activity attainment, andsleep hygiene, commonly accompany acute medical events such as surgeries among middle aged and olderadults. These sudden changes are associated with poorer long-term cognitive and brain outcomes. The Covid-19 pandemic caused a different version of sudden change: large numbers of healthy adults became confined tothe home for extended periods of time, changed their patterns of food shopping, restaurant eating, sports andexercise engagement, and sleep due to home confinement orders and their lingering after-effects. The Covid19pandemic is promoting a new and different form of sudden change in CV and lifestyle factors, the healthimpacts of which are not clear. Our immediate goal in this supplement is to rigorously assess the extent ofsudden CV risk factor changes associated with the Covid-19 pandemic, with a long-term goal of assessingrelationships between such cardiovascular changes and cognitive and brain changes in a large epidemiologicalcohort. This supplement will use validated technologies to objectively assess Covid-19-related changes to diet,physical activity, and sleep among black and white men and women in mid-life who have participated in theBogalusa Heart Study (BHS) participants, and already consented to longitudinal assessment of CV risk factors,brain outcomes, and cognitive outcomes via their enrollment in the parent grant (RO1 AG041200). We willprovide 250 BHS participants with wrist-worn accelerometers capable of assessing sleep quality and physicalactivity attainment (ActiGraph WGT3X+) as well as Remote Food Photography Methods© implemented via asmartphone application (the SmartIntake® app). Physical activity and sleep quality will be objectivelymeasured over a 7-day period, and food intake over a 4-day period. This data, together with previousassessments of diet, physical activity, and sleep quality from earlier sweeps through the cohort, will position usto calibrate and analyze changes in these three CV risk factors due to the Covid-19 pandemic. This data willposition us to assess effects of such sudden CV risk changes on cognitive and brain outcomes, as well as racedisparities in this association, to clarify the long-term public health impact of pandemic-related lifestylechanges. The data collected by this supplement efficiently leverages the parent grant (focused on CV risks andbrain outcomes) in a population with substantial minority representation (35% African-American) and couldidentify targets for a novel lifestyle intervention to be rapidly deployed and scaled in a future pandemic as away to preserve health. Leveraging the long-standing NIH investment in the Bogalusa Heart Study is theoptimal approach for investigating the effects of pandemic-related sudden CV risk factor changes on cognitiveand brain health.",2020,2024,Tulane University Of Louisiana,369440,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2012 +C09513,3R01AG062309-02S1,Supplemental Funding Request for RF1 AG062309 Early life glycemic status and Alzheimer's disease neuroimaging markers in middle age: the Bogalusa Heart Study,"The parent study (R01AG062309) examines associations between lifespancardiometabolic exposures and midlife brain structure and function, as well as midlifecognitive function, in the bi-racial, semi-rural Bogalusa Heart Study (BHS). Theimportance of the main study is that it clarifies which cardiometabolic exposuresinfluence the brain health of a socioeconomically diverse group of African American andwhite individuals at the portion of the lifespan (the 50s and early 60s) when cognitiveand brain health begins to become more heterogeneous and begins to include clinically-significant cognitive decline in a large number of persons. This supplement adds threeadditional cardiometabolic exposures to the set of exposures we will examine: suddenreductions in physical activity, diet quality, and sleep quality caused by Covid-19 relatedhome confinement. BHS participants will receive the same set of diet, physical activity,and sleep questionnaires that are assessed at each of their prior BHS study visits, alongwith a new survey specifically designed to identify Covid19-related changes. There is anextreme time urgency to assessing such confinement-related sudden lifestyle changes:BHS participants are confined to the home now, and are therefore able to assess theirown confinement-related lifestyle changes now, rather than rely on error-prone recall ofdistal events. The supplement significantly enhances the parent study by providing dataon exactly the sort of sudden, event-driven cardiometabolic changes that are importantto long-term outcomes, but are typically missed by a longitudinal cohort study such asBHS, whose structure lends itself to measuring slowly-varying changes over the courseof years. The supplement could clarify the importance of such sudden lifestyle changesto long-term health, relative to such slowly time-varying changes. In so doing, thesupplement could clarify the importance of rapidly deploying lifestyle interventions tohome-confined individuals to support high diet quality, physical activity attainment,and sleep quality in the event of a future pandemic.",2020,2023,Tulane University Of Louisiana,310085,Human Populations,Black | White,Adults (18 and older) | Older adults (65 and older),Other,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C09514,3R01DK124664-01S1,COVID-19 Testing and Linkage to Care with African American Church and Health Agency Partners,"PROJECT SUMMARYAfrican Americans (AA) are disproportionately burdened by COVID19 across the spectrum of related cases,hospitalizations, and deaths compared to Whites. Many multilayered barriers increase risk for COVID19 amongAA including poverty, essential jobs with increased virus exposure, cultural norms (eg, risk denial,medical/contact tracing mistrust), and limited access to healthcare and other services/resources. Thesebarriers highlight the need for accessible, trusted COVID19 testing and linkage to care (LTC) services (eg,health, prevention programs, community resources, contact tracing) to help slow COVID19 spread in AAcommunities. The AA church is an institution with extensive influence in AA communities and may be an idealsetting for increasing reach of COVID19 testing and LTC in hard hit AA communities. Yet, no controlled AAchurch-based studies exist on COVID19 testing interventions. The primary aim of this study is to fully test aculturally/religiously-tailored, church-based COVID19 testing and LTC intervention condition against a non-tailored intervention condition on COVID19 testing rates at 6 months with adult AA church members and thecommunity members they serve. Churches will be matched on membership size, denomination and pastparticipation in church health intervention studies, then randomized to treatment condition. Sixteen churches (8churches/arm; 45 church and 15 community members/church; N=960 total) will participate in the study. LTCuse, contact tracing approval, and COVID19 prevention behaviors will also be examined at 6 months assecondary outcomes. Guided by the Theory of Planned Behavior and Socioecological Model, our community-engaged approach includes trained church leaders delivering a culturally, church-appropriate COVID19 Toolkitinclusive of digital tools: a) individual self-help materials and tailored text messages; b) in-person/virtual groupseminars for caregivers of persons with COVID19; c) in-person/virtual church services with COVID19 relatedmaterials/activities (e.g., sermons, testimonials, responsive readings); and d) church-community level LTCservices (eg, insurance, healthcare, prevention programs, community resources, contact tracing) providedvirtually by community health workers, church-community-based re-opening guidelines, and church-basedCOVID19 testing events with health agencies. Examination of LTC use and contact tracing approval will aid inunderstanding intervention impact on COVID19 testing by addressing participant essential needs. Potentialmediators/moderators related to receipt of COVID-19 testing will be evaluated, and a process evaluation todetermine implementation facilitators, barriers, and fidelity related to increasing COVID19 testing rates. Ourongoing meetings with our long-term faith and health partners is enabling us to quickly adapt our AA church-based HIV testing and diabetes prevention interventions for the proposed study. This multilevel study couldprovide an effective, scalable model for increasing COVID19 testing, prevention, and LTC/contact tracingapproval with AA churches in partnership with health agencies, and provide strategies to streamlinedelivery/uptake of future COVID-19 vaccination.",2020,2022,University Of Missouri Kansas City,1439677,Human Populations,Black,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health | Innovation,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions | Community engagement,2021 +C09515,1R44DE030842-01,A scalable aptamer-based electrochemical biosensor for rapid detection of SARS-CoV-2 from saliva,"AbstractThe COVID-19 pandemic is a critical global public health emergency and many countries are failing to containthe virus's spread due to slow and insufficient testing. While several diagnostic methods are now available, mosttests are either reagent-intensive and must be done in CLIA-approved labs, making them expensive and slow toreport results, or rapid and inexpensive, but potentially lacking in sensitivity. In the U.S., seriously ill and high-risk patients have been prioritized for testing, causing states to miss mild and asymptomatic cases, some ofwhich are the most effective spreaders of the virus. However, expanding testing has been a challenge due toshortages of sampling swabs and key reagents for nucleic acid amplification-based tests, which are the mostpopular option. Testing capabilities must be expanded exponentially to enable mass population-level testing ofall patients, healthcare workers and their families, other critical key workers, and the wider community in orderto bring the pandemic under control. mPOD proposes to expand testing capabilities through a novel biosensorthat will use oligonucleotide molecules called aptamers to bind to unique sites on the SARS-CoV-2 virus.Aptamers have similar binding affinities to antibodies, but due to their smaller size, they are more agile, makingthem particularly suited for high-specificity binding. To complete the test, a saliva sample will be loaded onto atest strip containing aptamers immobilized onto gold electrodes. The gold-electrode test strip will be inserted intothe mPOD DTCT, a proprietary electrochemical test platform where virus-bound aptamers will be detected viacyclic voltammetry, triggering a positive result. The result is sent wirelessly via a mobile app, which sendsencrypted data on to the cloud for storage and to public health agencies for enhanced data collection, tracking,and tracing of COVID-19. The app will also include a backend database to help businesses, manufacturers,schools, and large institutions track tested individuals' results and tailor specific public health responses. In orderto further develop this technology and enable rapid deployment for timely COVID-19 intervention, mPOD plansto 1) Select SARS-CoV-2-specific aptamers for use in electrode test strips with an optimized signal-to-noise ratioperformance, 2) Demonstrate sensitivity and specificity of a low-cost, miniaturized potentiostat test strip for useas a COVID-19 POC or OTC diagnostic, 3) Complete and test a fully-fledged digital infrastructure for datacollection, tracking, and tracing of COVID-19 test results via the mPOD mobile app. This non-traditional approachwill provide new testing capabilities with the potential to report results faster than standard RT-PCR tests andwith greater accuracy and sensitivity compared to existing antigen-based diagnostics. Furthermore, once thesystem is developed, test strips with customized aptamers can be developed for rapid diagnosis of otherpathogens, including future emerging pandemics, via routine POC and OTC testing.",2020,2022,Mpod Inc,502248,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09516,3R01DA051302-01S1,Increasing representation of black communities in SARS-CoV-2 serosurveys by understanding barriers and motivations for participation,"AbstractRacial minorities have disproportionate risk for SARS-CoV-2 diagnoses and adverse outcomes includingdeath. Burden of disease in Black populations is likely underestimated due to sub-optimal access to, andusage of, SARS-CoV-2 testing. Serosurveys, which use probability-based methods to select persons forSARS-CoV-2 testing and an accompanying survey, have potential to improve our understanding of population-level burden of disease and risk factors for infection. However, early results from U.S.-based serosurveysindicate sub-optimal participation rates among Black populations, which results in their under-representation inburden of disease estimates and a limited understanding of risk factors for infection. The current project aimsto identify barriers and motivations for participation in population-based SARS-CoV-2 serosurveys amongdiverse Black sub-populations (e.g. by gender, age, and education level). Understanding factors that influenceBlack people's decision-making about serosurvey participation and how these factors differ by socio-demographic characteristics will allow us to provide tailored recommendations for increasing Black populations'participation in serosurveys and representation in burden of disease estimates. Our interdisciplinary team ofepidemiologists, behavioral scientists, and community health advocates/practitioners will use qualitative andquantitative methods in the context of serosurveys to understand how influences on decision-making arerelated to actual decisions about participation in SARS-CoV-2 antibody testing. Our qualitative interview guidewill be informed by the family of value expectancy theories and will be developed in collaboration with acommunity advisory board (CAB), who will also help us to identify community constituents for participation inqualitative interviews. Key themes from the qualitative interviews, and language used by respondents, willinform a quantitative survey instrument, which will assess relative strengths of influences on serosurveyparticipation and how they differ socio-demographically across Black sub-populations. Our Specific Aims are:(1) Convene a community advisory board (CAB) comprising leaders from organizations serving Blackcommunities in Atlanta (e.g., professional, faith-based, health and social services); (2) In the context of aSARS-CoV-2 serosurvey, conduct 50 semi-structured interviews about barriers and motivations for serosurveyand vaccine participation with Black persons from 3 diverse neighborhoods, representing a range of socio-demographic characteristics; (3) Determine the distribution of barriers and motivations for serosurveyparticipation across socio-demographic subgroups of 2,000 Black persons using a quantitative survey. We willprovide recommendations for increasing participation of black communities in SARS-CoV-2 serosurveys, whichis critical as SARS-CoV-2 serosurveys are likely to be used for on-going disease surveillance in the U.S. and toinform both resource allocation and design and monitoring of prevention and control strategies.",2020,2022,Georgia State University,621604,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Approaches to public health interventions | Community engagement,2020 +C09517,1R61HD105590-01,Diagnosing and predicting risk in children with SARS-CoV-2- related illness,"In the wake of COVID-19 pandemic, Multisystem Inflammatory Syndrome in Children (MIS-C) has evolved as anew threat to children exposed to SARS-CoV-2. The emergence of MIS-C is so new and so rapidly evolvingthat there are currently no diagnostic tests to identify these patients nor are there tools to predict diseaseprogression. Through established, funded, multi-center consortia in the U.S. (CHARMS: Characterization ofMIS-C and its Relationship to Kawasaki Disease funded by PCORI) and the UK (DIAMONDS), we will collectclinical data and samples to support the proposed studies. First, we will generate transcript, protein andantibody datasets from children with COVID-19, MIS-C, and with other febrile illnesses. Next, we will use thesedata to devise tests to distinguish children at risk of progression to severe COVID-19 or MIS-C and diagnostictests to distinguish these conditions from other causes of fever in children. Continuing our establishedcollaboration with Columbia University, we will define the antibody repertoire against all known humancoronaviruses and determine how pre-existing antibody to other coronaviruses may shape the immuneresponse in acute SARS-CoV-2 infection and MIS-C. The first two years (R61) will build on the expertise of theassembled teams to discover unique proteomic and transcriptomic patterns in MIS-C and SARS-CoV-2-infected patients and relate clinical parameters to the antibody response to coronaviral antigens profiled onpeptide arrays. This work will leverage already banked plasma, serum, and RNA samples from children withCOVID-19, MIS-C, Kawasaki disease and other inflammatory conditions. Rigorous Go/NoGo criteria havebeen established and will determine progression to the R33 phase. The final two years (R33) will focus onplatform development and multicenter and bi-national test validation to diagnose and predict severity inchildren with SARS-CoV-2 infection or MIS-C based on aptamer technology, lateral-flow protein detection,point-of-service RNA or antibody profiling with commercial partners. De-identified clinical and molecular datawill be deposited in the RADx-rad hub to facilitate data sharing. Many potential hurdles in this type of researchhave already been overcome: a) IRB-approved patient recruitment for data and samples is on-going, b) clinicalsamples have been banked, c) strong preliminary data has been generated on RNAseq, aptamer proteomics,and coronaviral antibody responses, and d) the teams have a strong track record of previous collaboration andproductivity. The synergistic expertise of these investigative teams in this multi-center proposal provides aunique opportunity to create diagnostic and prognostic tools for children suffering from the spectrum of SARS-CoV-2 illnesses.1",2020,2022,University Of California-San Diego,698415,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2021 +C09518,1U01TR003734-01,Efficacy of Fenofibrate for COVID-19: A phase II randomized controlled trial,"PROJECT SUMMARYAging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydratemetabolism are risk factors for death in Coronavirus disease 2019 (COVID-19). Recent studies suggest thatCOVID-19 infection of human lung primary bronchial epithelial cells is dependent on metabolic mechanismsincluding a marked shift in cellular metabolism that leads to excessive intracellular lipid generation. In this cellculture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple otherregulatory agencies around the world to treat dyslipidemias) at concentrations that can be achieved clinically,markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may bebeneficial in the setting of COVID-19. We propose an international multicenter randomized placebo-controlled trial to assess the impact offenofibrate on outcomes in patients with COVID-19. We will administer fenofibrate (145 mg/d of Tricor or dose-equivalent preparations for 10 days, with dose adjustment in chronic kidney disease [CKD]) will be tested. Ourprimary endpoint will be a global score that ranks patient outcomes according to 5 clinically important patient-centric outcomes. Out hierarchical endpoint achieves high statistical power and thus maximized the likelihoodof productive phase II trials that can readily identify potential therapies for advance into phase III trials. We willassess various secondary and exploratory endpoints. Finally, we aim to consolidate an international networkthat can rapidly execute phase II trials in COVID-19, leveraging established collaborations with COVID-19clinical researchers in Latin America. This network can readily execute this trial and support other NIH-fundedtrials. Our proposal has the potential to advance a novel therapy (fenofibrate), a widely available, generic andinexpensive drug with a proven track record of safety. If fenofibrate is effective for COVID-19, our trial couldhave a major public health impact on the COVID-19 pandemic.",2020,2021,University Of Pennsylvania,1328303,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Phase 2 clinical trial,2021 +C09519,1R61HD105618-01,Discovery and clinical validation of host biomarkers of disease severity and multi-system inflammatory syndrome in children (MIS-C) with Covid-19,"ABSTRACTNovel approaches for early and accurate diagnosis of COVID-19 associated syndromes andevaluation of clinical severity and outcomes of COVID-19 disease in children are urgently needed.The overarching goal of this grant proposal is to develop clinical assays that can evaluate and predictseverity of pediatric COVID-19 disease, ranging from asymptomatic or mildly symptomatic to severemanifestations such as multisystem inflammatory syndrome (MIS-C). To date, we have collected andbiobanked clinical samples from more than 400 patients across 3 academic hospitals, includingapproximately 100 patients with MIS-C. In the first R61 phase of this project, we will continue to enrollpatients with pediatric COVID-19 and MIS-C for sample collection and longitudinal chart review andtesting (Aim 1), leverage machine learning to identify diagnostic and prognostic ""omics"" hostbiomarkers based on RNA transcriptome profiling from nasal swab and whole blood samples (Aim 2)and cell-free DNA analysis from plasma (Aim 3), and generate predictive models of clinical severityand outcomes by incorporating longitudinal clinical, laboratory, viral, and omics data (Aim 4). Ourrationale for including these samples is that they are routinely obtained in hospitals and clinics andpermit easy and noninvasive collection without any special processing or handling requirements,which will accelerate the development of omics-based clinical assays. Our Go/No-Go transitionmilestones for transition to the R33 phase after 2 years include: (1) collection of longitudinal samplesfrom a minimum of 120 patients for each identified presentation (mildly symptomatic outpatient,severely ill in the ICU, and MIS-C) and a comparable number of matched controls, (2) generation ofpanels of candidate of severity and confirmation of a subset of biomarkers by qPCR, (3) developmentof classifier models using machine learning using the biomarkers alone (for clinical assaydevelopment), and (4) combining these omics biomarkers with additional clinical, viral, and laboratorybiomarkers into combined classifier models using machine learning. For the classifier models, theminimum/goal performance requirements would be 70%/>80% sensitivity and 80%/>90% specificity.In the second R33 phase, we propose to develop host-based clinical assays for diagnosis andseverity prediction of COVID-19-associated syndromes, including MIS-C, in children from nasalswabs and blood (Aim 5) and validate these biomarker panels as a Laboratory Developed Test (LDT)in a CLIA (Clinical Laboratory Improvement Amendments) diagnostic laboratory (Aim 6). Theseassays will be evaluated for accuracy, precision, reproducibility, limits of detection (LOD), matrixeffect, interference, among other performance characteristics. We will work closely with the RADx-radData Coordination Center (DCC) on assay development, testing, and validation for submission to theFDA for Emergency Use Authorization (EUA) and timely deployment of these assays for clinical use.",2020,2022,University Of California-San Francisco,863810,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2021 +C09520,1U01AA029331-01,Nanobody-Based Electrochemical Biosensor for Real-Time Detection of Aerosolized SARS-CoV2,"ABSTRACT/PROJECT SUMMARY Coronavirus 2019 (COVID-19) has afflicted 6.2 million Americans and killed 190,000 as of early September2020 (WHO website); a roughly 3% mortality. Between a shortage in testing and unidentified asymptomaticindividuals, the actual number of those infected could be 6 to 24-fold higher than that reported. SARS-CoV-2(CoV-2), the virus underlying the disease, results in a range of symptoms; in select cases a severe respiratoryillness that impedes breathing that could lead to hospitalization and death. CoV-2 is transmitted person-to-person via inhalation of the virus through mucosal membranes of the nose and throat from transfer aftertouching a contaminated surface or by inhaling aerosolized virus. Unfortunately, COVID-19 is likely to beprevalent well into 2021 and beyond. We must increase our ability to test for CoV-2. First, testing is needed to diagnose individuals that aresymptomatic or asymptomatic to reduce community spread. And second, monitoring gathering areas forairborne virus that could inform the decision to shutdown a space or implement disinfection and mitigation ofan area. We propose to use an electrochemical biosensor in two detection devices, 1) a diagnosticbreathalyzer for instant detection of CoV-2 and 2) an airborne detector for real-time, continuous surveillance ofa large space. We have developed a novel ultra-sensitive, antibody-based electrochemical biosensor to detect CoV-2repeat binding domain (RBD) spike protein. The technology is based on a micro-immunoelectrode (MIE)biosensor pioneered by the Cirrito laboratory to study protein dynamics in the setting of neurodegeneration (2,3).The biosensor uses voltammetry to measure the oxidation of tyrosine amino acids; oxidation is the release ofelectrons that the biosensor measures as a change in current. Antibodies are covalently attached to theelectrode surface to provide selectivity. Our prototype CoV-2 biosensor is sensitive to 2 femtogram/ml,compared to several current CoV-2 antigen tests that are sensitive to the low picogram/ml range. The proposal will first (Aim 1) optimize our CoV-2 biosensor to detect CoV-2 viral particles, as well as testseveral parameters to increase sensitivity and longevity. Aim 2 will build a test breathalyzer that will utilize anebulizer to generate virus laden air containing aerosol droplets similar to a breath that contain definedconcentrations of CoV-2 viral particles. Aim 3 will test the airborne biosensor in a realistic environment. Co-IChakrabarty's laboratory has unique capabilities of mimicking real-world environmental conditions, especiallyin the context of atmospheric aerosols, necessary for testing and optimizing the biosensor's performance forfield deployment. Atmospheric conditions include relative humidity (RH) and temperature, as well as commonairborne pollutants found indoors. Finding novel means to detect the CoV-2, as well as create a platform to detect other and futurepathogens, would enable us to limit the viral spread throughout the community in the current and futurepandemics.",2020,2022,Washington University,433266,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Diagnostics | Barriers, PPE, environmental, animal and vector control measures",2020 +C09521,1U01DA053976-01,Wastewater Analysis of SARS CoV-2 in Tribal Communities,"ABSTRACTThe rapid onset of the COVID-19 pandemic left many across the world unprepared to test, treat, and plan forcoronavirus morbidity and mortality. This was true for Tribal nations, whose sovereign status enabled swift andpreventative measures such as lock-downs and border closures, yet whose culture contributed to additionalunique risk factors. Among those are testing disparities, underlying health factors, and community infrastructure.However, clinical testing doesn't capture the extent of positive cases, and without the collective efforts of thisproject, Tribes will likely not be included in wastewater-based epidemiology (WBE) analysis, which has garneredwide-spread interest due to its ability to generate data in advance of community infectivity. In this project, we willshow that WBE is a non-invasive, culturally appropriate biomonitoring strategy that can be adopted andimplemented by Tribal communities to empower them with a practical, yet technologically advanced healthsurveillance tool. Building upon a rigorous methodology of Tribal consultation and community-based participatoryresearch, assessment of wastewater and community infrastructure, and training of Tribal wastewater operatorsand health administrators on WBE, we will form the WBE Tribal Coordination Center. Tribes will be recruitedthrough the InterTribal Council of Arizona's National Tribal Water and Wastewater Operator Training Programnetwork. We will measure coronavirus in wastewater across U.S. reservations using established RT-qPCRtechniques and a novel protein quantification method, and we will sequence viral RNA extracts to assess SARS-CoV-2 variants in Tribal communities. Risk factors contributing to elevated COVID-19 in Tribal communities willbe quantified with integration of geospatial analysis. Frameworks for risks from numerous environmentally-transmitted pathogens have been developed by our team, setting a foundation to incorporate variability anduncertainty for Tribal settings with qualitative information from Tribes in order to appropriately scope our modelingefforts. Simulation results will help to target resources efficiently for monitoring and public health interventionsby identifying specific sampling locations where it is most likely to detect SARS-CoV-2 given other communityand scientific constraints. Information from the RADx Data Coordination Center will be used to the fullest extentto compare Tribal communities with their non-Tribal counterparts. Through the coronavirus pandemic andbeyond, Tribes will be better informed of their ability to use WBE to measure community health, therebyprotecting community health and building capacity for future applications and research translation.",2020,2022,Arizona State University-Tempe Campus,1494765,Human Populations | Environment,Unspecified,Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control | Research to inform ethical issues","Diagnostics | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping | Barriers, PPE, environmental, animal and vector control measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +C09522,1U01DC019578-01,SCENTinel: A Rapid Smell Test for COVID-19 Surveillance,"PROJECT SUMMARYSmell loss is a predominant symptom of COVID-19, and initial evidence based on self-reports suggests thatchemosensory loss is a sensitive predictor of COVID-19 in the general population, more so than fever.However, given the natural lack of awareness of chemosensory changes, self-reports underestimate the trueprevalence of smell loss in patients with COVID-19 by 20% compared to an objective test. Therefore, wepropose testing and deploying a rapid and objective measure of smell ability, the SCENTinel test, inspired bythe NIH Toolbox® Odor Identification Test that our team previously developed. SCENTinel is an inexpensive,and convenient smell test for COVID-19 surveillance of the population that quickly and easily assessesthree smell loss factors: odor detection, odor intensity, and odor identification. It is designed for practical use inseveral contexts, including high-density areas such as community medical sites, universities, subacute carefacilities, and both industrial and nonindustrial workplaces. Our multi-disciplinary team has expertise inunderstanding taste and smell, developing and validating chemosensory tests, as well as studying the broadsymptomatology of COVID-19. The group is led by MPI Dalton from the Monell Chemical Senses Center, anexpert in human olfaction and designing olfactory tests; MPI Parma from Temple University is an expert inCOVID-19 smell loss, is the Chair of the Global Consortium for Chemosensory Research, and has expertise inconducting research in rapidly changing situations; Dr. Schalet and his team at Northwestern University andDr. Chun and his team at Yale University, among the other established and interested partners (Fox subacutenursing homes, Hormel Food). Our team also includes the Director of Technology Transfer at the MonellCenter, Dr. O'Leary, to explore potential partners and expand SCENTinel deployment nationwide. Dr. Reedfrom the Monell Chemical Senses Center will work directly with the Data Coordination Center, drawing on herexperience in managing large shared NIH datasets. All will work closely with the NIH Project Scientist. Thisproposal aims to a) fine-tune SCENTinel's ability to predict a positive COVID-19 diagnostic test; b) examine marginal smell loss as a sign of the earliest phases of COVID-19, before a positive diagnostic test; and c)assess the test's psychometric validity with test-retest reliability measures and validation against the NIHToolbox® Odor Identification Test. Together, these aims will establish a standardized protocol for use ofSCENTinel as a rapid and objective smell test that can easily be incorporated into onsite COVID-19 testingcenters, schools, and workplaces nationwide. Furthermore, it will provide key insights into early-onsetchemosensory symptoms in relation to a confirmed COVID-19 diagnosis, providing a crucially needed meansto contain the spread of COVID-19.",2020,2023,Monell Chemical Senses Center,502671,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09523,1U18TR003795-01,Portable GC detector for breath-based COVID diagnostics,"Project Summary/Abstract: This proposal has two major goals: 1) Define signature exhaled breath volatileorganic compounds (VOCs) to diagnose SARS-CoV-2 infections, and 2) Develop a portable chemical sensingdevice that can capture and detect exhaled VOCs and includes machine learning algorithms for automateddata processing and results interpretation. This project will bring a portable sensor forward into clinical use withthe aim of supplementing COVID-19 diagnostics with a reagentless alternative. Breath testing of exhaled VOCbiomarkers is a relatively new concept that has the potential to transform healthcare in the US and globally.Our overarching hypothesis is that a miniature breath analysis device can measure signatures of exhaledbreath VOCs in real-time and correlate their profile to viral upper respiratory infections such as SARS-CoV-2,even asymptomatically. In Aim #1, we propose a prospective, observational study to analyze breath samplesfrom COVID-19 positive and negative subjects, solely for the purpose of analysis through gold standard GC-MS to define breath VOC biomarkers of infection. We will recruit subjects at two local sites, the UC DavisMedical Center (Sacramento, CA) and VA Northern California Health Care System (Mather, CA), where MPIDr. Kenyon and Co-Is Drs. Harper and Schivo have joint clinical appointments. Our group has a proven trackrecord to conduct these types of clinical breath studies. In Aim #2, we will develop a portable breath analysisdevice using our novel miniature differential mobility spectrometry (DMS) detector, coupled with chip-basedgas chromatography. DMS is a subset of ion mobility spectrometry and detects VOCs at ambient temperaturesand pressures, making it highly appropriate for portable devices. This device would include our custom chip-based preconcentrator, which is packed with a chemical sorbent for extraction of VOCs from breath, and willcompare functionality of a compact commercially available GC column to a micro-GC column chip fromDeviant, a subcontractor in this work. Individual components of this device have already been developed, andunder direction of MPI Prof. Davis, Chair of Mechanical and Aerospace Engineering, a team of researchengineers would integrate these pieces together into a single unit. Collaborator Prof. Chuah would guidedevelopment of a custom software package for the device with machine learning and artificial intelligencecapabilities for automated data processing and interpretation. The device would be placed in the hands ofclinicians, who would provide feedback that engineers would immediately incorporate into the device andreturn to the clinicians for more testing. Under Aim #3, our team would process the GC-MS and GC-DMS datagenerated in this work, identifying a novel VOC profile for COVID-19 diagnostics. Aim #4 would initiate towardsthe end of this study to develop both a regulatory pathway & contract manufacturing plan for large scaleproduction and deployment of the device for clinical approval. These efforts are supported by collaborator Dr.Nam Tran, Director of Clinical Pathology & Clinical Chemistry at the UC Davis Medical Center.",2020,2022,University Of California-Davis,975463,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2020 +C09524,3P01AI073693-11A1S1,Effect of Covid-19 engagement of ACE2 on brain health and pathology,"AbstractThere are mechanisms in the brain that regulate interactions between neurons and microglialcells and promote homeostasis. These are perturbed in several diseases includingneuropsychiatric lupus, NPSLE, studied in this PPG, and following sepsis. Many conditions ofneuroinflammation are characterized by microglial activation, and, as a consequence of thisactivation, by neuronal dendritic pruning and an impaired blood brain barrier. Interestingly, apathway regulating homeostasis in the brain and dysregulated by neuroinflammation is therenin-angiotensin system. Angiotensin II is generated by angiotensin converting enzyme, ACE,and binds to a receptor AT-1 to enhance inflammation. ACE inhibitors or angiotensin receptorblockers, ARBs, can improve neuroinflammation by either decreasing production or neutralizingangiotensin II. In this pathway, ACE2, a membrane-bound protease, also functions to destroyangiotensin and to generate a small angiotensin peptide, ang1-7, that is anti-inflammatory.ACE2 is the cellular receptor for Covid-19, and binds the viral spike protein, S, more specifically,the receptor binding domain, RBD. This study will examine the binding of S and RBD to normalmouse brain and to mouse brain mimicking NPSLE or sepsis survival. We will further studywhether engagement by S or RBD alters the functional state of neurons, microglia and brainendothelial cells. Finally, we ask whether the use of ACE inhibitors or ARBs alters S or RBDbinding, and whether S or RBD impair the efficacy of these medications in halting or reversingthe neurodegenerative process in NPSLE and in sepsis survivors. This study cannot beperformed in humans, but it has important translational implications.",2020,2022,Feinstein Institute For Medical Research,196504,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C09525,3UG1DA050071-02S1,Leveraging Social Networks to Increase COVID-19 Testing Uptake: A Comparison of Credible Messenger and Chain Referral Recruitment Approaches,"Until the advent of treatment or a vaccine, our ability to contain COVID-19 must rely on widespreadidentification of (asymptomatic) positive cases, their subsequent quarantine, and contact tracing of thosepotentially exposed. Therefore testing efforts must be targeted to those highly vulnerable yet unservedpopulations, including individuals who use opioids and other substances. These individuals may have poorrespiratory or pulmonary health due to substance use (e.g. opioids, methamphetamine), which may make themmore susceptible to the virus. Also, these individuals are also more likely to have been incarcerated, or resideon the street, in shelters or in crowded accommodation, further placing them at risk for transmission. Wepropose research to establish efficacy and sustainability of a community-social network outreach model thatpartners infectious disease health providers with community based organizations to successfully implement(reach, uptake, delivery and sustainment) COVID-19 point of service, rapid-testing among a highly vulnerableand often underserved population, those who use opioids and other substances. Two distinct social networkrecruitment strategies with demonstrated efficacy identifying hidden populations and increasing uptake of HIVtesting will be adapted and compared. Guided by the EPIS framework, social cognitive theory, and Andersen'smodel, this study comprises three phases. Phase 1: Adaptation of outreach recruitment strategies, we willwork with our project community advisory board (CAB) to adapt chain-referral and credible messenger strategiesfor uptake of COVID-19 testing, to finalize recruitment and on-site testing protocols, and to train the CAB in thenew protocols and in continuous quality improvement strategies (Aim 1). Phase 2: Strategy Efficacy Trial andImplementation Evaluation, we will compare the two strategies in a cross-over design at two community basedorganizations (CBOs) with long standing history of serving hard-to-reach populations in their communities. Thecomparison of strategies is not to identify the statistical superiority of one sampling strategy in providingpopulation estimates over the other, but instead to identify the ability of each recruitment strategy to reach thetarget population and increase uptake of COVID-19 tests. We will examine the impact of each strategy on (i)reach (recruitment of target population), (ii) COVID-19 testing/repeat testing, and (iii) service delivery (i.e.quarantine, medical care and contact tracing) among those who test positive for COVID-19 (exploratory) (Aim2). Phase 3: Sustainment, CBOs will implement the strategy proven efficacious based on outcomes, and wewill examine their sustainment of the program (Aim 2). Implementation evaluation will identify participant-, staff-,and organizational-level factors that influence the feasibility, acceptability, and sustainability of each strategy inthese CBOs. (Aim 3). This investigation will provide much needed information to improve health outcomes and toidentify effective system-level responses to prevent or arrest the spread of COVID-19 among the social networksof those who use opioids and other substances, a highly vulnerable and often overlooked population.",2020,2022,Columbia University,793293,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09526,1U18TR003812-01,COVID-19 detection through scent analysis with a compact GC device,"Recent studies, including ours, have suggested that breath may allow us to diagnose COVID-19 infectionand even monitor its progress. As compared to immunological and genetic based methods using sample medialike blood, nasopharyngeal swab, and saliva, breath analysis is non-invasive, simple, safe, and inexpensive; itallows a nearly infinite amount of sample volume and can be used at the point-of-care for rapid detection.Fundamentally, breath also provides critical metabolomics information regarding how human body responds tovirus infection and medical intervention (such as drug treatment and mechanical ventilation). The objectives ofthe proposed SCENT project are: (1) to refine automated, portable, high-performance micro-gaschromatography (GC) device and related data analysis / biomarker identification algorithms for rapid (5-6minutes), in-situ, and sensitive (down to ppt) breath analysis and (2) to conduct breath analysis on up to 760patients, and identify and validate the COVID-19 biomarkers in breath. Thus, in coordination with the RADx-radData Coordination Center (DCC), we will complete the following specific aims.(1) Refine 5 automated micro-GC devices to achieve higher speed and better separation capability. Wewill construct 5 new automated and portable one-dimensional micro-GC devices that require only ~6 minutes ofassay time (improved from current 20 minutes) at the ppt level sensitivity (Sub-Aim 1a). Then the devices will beupgraded to 2-dimensional micro-GC to significantly increase the separation capability (Sub-Aim 1b). In themeantime, we will optimize and automate our existing data processing and biomarker identification algorithmsand codes to streamline the workflow so that the GC device can automatically process and analyze the datawithout human intervention (Sub-Aim 1c).(2) Identify breath biomarkers that distinguish COVID-19 positive (symptomatic and asymptomatic) andnegative patients. We will recruit a training cohort of 380 participants, including 190 COVID-19 positive patients(95 symptomatic and 95 asymptomatic) and 190 COVID-19 negative patients from two hospitals (MichiganMedicine - Ann Arbor and the Henry Ford Hospital - Detroit). We will conduct breath analysis using machinelearning to identify VOC patterns that match each COVID-19 diagnostic status.(3) Validate the COVID-19 biomarkers using our refined micro-GC devices. Using the refined 2-D micro-GCdevices from Sub-Aim 1b, we will recruit a new validation cohort of 380 participants (190 COVID-19 positivepatients and 190 COVID-19 negative patients) to validate the biomarkers identified in Aim 2. We will leverage existing engineering, data science, clinical, regulatory, and commercialization resourcesthroughout the project to hit our milestones, ensuring a high likelihood of rapid patient impact. Upon completionof this work, we will have a portable micro-GC device and accompanying automated algorithms that can detectand monitor COVID-19 status for people in a variety of clinical and community settings.",2020,2022,University Of Michigan At Ann Arbor,999775,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis,2020 +C09527,3U01AI100119-09S1,Development of lung T cell responses in infant respiratory immunity,"PROJECT SUMMARYThe emergence of SARS-CoV-2 has resulted in a worldwide pandemic. Infection with SARS-CoV-2 causes aspectrum of disease symptoms ranging from asymptomatic and mild/self-limited disease, to severe diseaseassociated with significant lung damage and high levels of morbidity and mortality. As all individuals areimmunologically naïve to this virus and there are currently no targeted treatments or vaccines against SARS-CoV-2, protection and recovery depend on our own immune responses and supportive clinical care. Initially,children experienced largely asymptomatic or mild disease with severe disease resulting in significant lunginjury a rare occurrence. However, a new multisystem inflammatory disorder in children (MIS-C) related toSARS-CoV-2 has emerged as a late complication of infection. Children with MIS-C commonly present withcardiac dysfunction and shock, most closely resembling Kawasaki disease and toxic shock syndrome.Importantly, some children presenting with MIS-C have been reported to develop coronary artery aneurysms, afinding common to Kawasaki disease. The significant amount of mild/self-limited disease in children contrastedwith the excessive inflammation associated with SARS-CoV-2 suggests distinct immune responses.Additionally, the long-term implications, particularly to the cardiovascular system, of early life infection withSARS-CoV-2 remain unknown. We hypothesize that these distinct clinical manifestations in children, includinglack of symptomatic respiratory infection to SARS-Cov-2 is due to a robust and enhanced T cell response. Theaims of this proposal are to 1) Establish pediatric patient cohorts for comparing outcomes and immuneresponses across the spectrum of pediatric COVID-19 disease, 2) Define the pediatric immune response toSARS-CoV-2 and how it differs across the clinical spectrum of disease, and 3) Define the incidence of andpatient characteristics associated with sustained adverse cardiac outcomes for children with MIS-C andpediatric COVID-19. This project proposes to provide new insights into the pediatric immune and long-termcomplications of SARS-CoV-2 infection by employing a multi-disciplinary approach utilizing a team ofinvestigators including immunologists, pediatricians, and pediatric subspecialists (cardiology/critical caremedicine). These studies will provide invaluable insight that will help guide future decision making for treatmentand preventative strategies for children.",2020,2022,Columbia University Health Sciences,741976,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C09528,3U54MD000502-18S1,Obesity Health Disparities Research Center (OHDRC) - COVID-19 Testing Model among Vulnerable Populations: From Community Engagement to Follow-Up,"The COVID-19 pandemic has created unique challenges for vulnerable populations. As part of the mission ofthe OHDRC, we have maintained continuous community engagement and partnerships aimed at finding waysto reduce the impact of obesity and related chronic diseases. With the advent of COVID-19, we were quicklyable to leverage these long-standing and trusting relationships to learn how COVID-19 was perceived by theresidents of our partnering vulnerable communities. Through ongoing community dialogue, we know that thereare substantial differences in how residents in our partner communities understand and act upon COVID-19guidance, perhaps contributing to the alarming disparities in COVID-19 outcomes. Overall, residents feel thatCOVID-19 is making marginalized communities even more marginalized. In this environment, it is vital that wefind ways to improve COVID-19 testing and follow-up care through collaboration with community partners.The overall goal of this emergency revision to the OHDRC, COVID-19 Testing Model among VulnerablePopulations: From Community Engagement to Follow-Up, is to implement and evaluate the impact of a three-component mobile community-based testing model in improving the access, acceptance, uptake, andappropriate follow-up. Our unique model combines 1) robust pre-testing community engagement to improvereach and acceptability of COVID-19 testing; 2) targeted mobile testing located in underserved neighborhoodsto increase access and uptake; and 3) culturally appropriate post-testing participant navigation and follow-upservices to ensure better impact and health outcomes. Strong community partnerships help ensure theacceptability and sustainability of this effort.The proposed model is guided by the Community Based Participatory Research (CBPR) framework andintegrates a Social Determinants of Health (SDH) approach throughout all aims to strengthen communityengagement, identify areas in greatest need for testing, and enhance navigation services to address unmethealthcare follow-up and social needs. We will compare the effectiveness of our neighborhood mobile testingmodel to the traditional health systems-based fixed testing model. Study findings will provide evidence thatcan help improve testing rates and follow-up among vulnerable populations and address stark disparities inCOVID-19 outcomes. The proposed work builds upon an already active demonstration pilot testing project thatprovided testing to vulnerable African American and Hispanic residents of Jefferson County, Alabama.",2020,2022,University Of Alabama At Birmingham,1576328,Human Populations,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Policy research and interventions,2003 +C09529,3K23AI136579-03S1,'Antibody Profiles and Genetics of Pernio-Like Lesions during the COVID-19 pandemic',"Project SummaryA subset of patients with coronavirus disease-2019 (COVID-19) develop cutaneous manifestations of theirsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including pernio of their feet andhands, known as ""COVID toes."" These patients tend to have a mild disease course, which may indicatesuccessful viral control by the host. By leveraging an existing patient cohort at Massachusetts General Hospital(MGH), and the extensive laboratory infrastructure at the NIH, this proposal aims to elucidate the complexdeterminants of a unique phenotype of COVID-19: pernio/ ""COVID toes,"" with the following Aims. Aim 1: Toevaluate genetic determinants of pernio-like lesions (""COVID toes"") in response to SARS-CoV-2 infection. Aim2: To characterize the inflammatory and serological response during acute infection and convalescence ofpatients with SARS-CoV-2 who develop pernio-like lesions as a symptom of COVID-19. Biological samples willbe obtained at MGH and sent to collaborating labs at the NIH. In particular, this proposal will help usunderstand the host immune response to COVID-19 by focusing on patients who have controlled the diseaseand have had relatively mild clinical courses, as characterized by their skin lesions. Successful completion ofour aims will immediately and directly respond to important gaps in our knowledge regardingmild/asymptomatic COVID-19, which in turn can help inform our understanding of how to harness this type ofsuccessful control for other patients.",2021,2021,Massachusetts General Hospital,53860,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C09530,1U18TR003787-01,A Handheld Microchip for GC analysis of breath to screen for COVID-19,"Project Summary The COVID-19 pandemic has caused unprecedented societal suffering and economic disruption. In theUnited States, more than six million people have contracted COVID-19 and more than one hundred ninetythousand patients have died of this disease to date. Although current COVID-19 diagnostic testing technologiesare critical for slowing the spread of the virus and preventing future outbreaks, they are not practical for field use.Current diagnostic tests are cumbersome to perform because they use aqueous solutions, require multiple steps,and hours-to-days to obtain results. Since the US began to reopen the economy in May, there has been asignificant increase in the number of COVID-19 cases. Therefore, there is an urgent need to develop a diagnosticapproach that is non-invasive, portable, and can rapidly provide test results. The overall goal of the project is to develop a mobile breath analysis technology for rapid screening forCOVID-19 using a handheld breath collection tool and a portable GC with a photoionization detector (PID). Thehandheld tool will be a closed system for trapping select volatile organic compounds (VOCs) on a microfabricatedchip. The captured VOCs will be eluted with ethanol and then analyzed using a commercially available, portableGC-PID instrument. Artificial intelligence (AI) and machine learning algorithms will be applied to recognize theVOC pattern that correlates with COVID-19 infection. The central innovation is the microfabricated chip thatcaptures carbonyl compounds in exhaled breath and thus serves as a preconcentrator, which enables analysisof carbonyl VOCs by the portable GC-PID. The hypothesis is that the carbonyl metabolome in exhaled breath isdirectly related to the body's reaction to the novel coronavirus infection, and changes in the carbonyl VOCcomposition in exhaled breath relative to healthy controls can be used to detect both symptomatic andasymptomatic COVID-19 patients. Three specific aims are proposed to fulfill the overall goal. Aim 1 is to build a disposable handheld breathanalyzer tool for concentrating carbonyl VOCs. Aim 2 is to identify VOC patterns in the breath of COVID-19patients by machine learning algorithms. Aim 3 is to integrate portable GC technology with the breath samplingtool for COVID-19 screening guided by an AI system. The University of Louisville is uniquely suited to rapidlytransition the microchip technology to field use because of the PI and Co-PI's experience in breath analysis andtranslational research, and the project team's experience in virology, infectious diseases, biostatistics, andartificial intelligence as well as the state-of-the-art facilities that include a MicroNano Technology Center,Biosafety Level 3 Regional Biocontainment Lab, and an NIH-funded REACH program.",2020,2022,University Of Louisville,1026672,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09531,3P30AI027763-29S1,Collaborative community networks to optimize implementation of low barrier COVID-19 testing efforts among diverse Latinx populations in Northern California,"Project SummaryThe health and economic effects of the COVID-19 pandemic in the United States are staggering, and personsof color in the US - already heavily impacted by structural inequities - bear a disproportionate burden ofCOVID-19 disease and death. Testing is a cornerstone of stopping the spread of the virus, yet in the UStesting rates remain far below target levels and current strategies are failing to reach the communities mostaffected. In California, despite initial success in limiting spread with the earliest shelter-in-place mandate in thenation, even partial attempts at easing restrictions have resulted in a surge in new cases. Currently, Californiahas the highest case count in the U.S and the pandemic is taking a disproportionate toll on Latinx individuals,many of whom are essential workers. An incomplete understanding of testing barriers and optimal strategies tomitigate these barriers among Latinx persons hampers the design of the scalable strategies needed toaccelerate equity in the reach, uptake, and preventative impact of SARS CoV-2 testing throughout the US.In this proposal, our objective is to evaluate community-engaged approaches to scale low-barrier COVID-19testing for Latinx communities and evaluate retesting strategies for priority groups in Latinx communities atincreased risk of infection. We will draw upon our experience with Latinx community-engaged mass SARS-CoV2 testing campaigns, expertise in community-based HIV testing trials informed by behavioral economicsand the success of San Francisco's Latinx Task Force for COVID-19 model. In Aim 1, we will evaluateimplementation of a Latino Task Force (LTF) collaborative network across 3 counties in Northern California(Marin, Merced and San Francisco), adapted from San Francisco's LTF model to promote locally-adaptedCOVID-19 test and respond initiatives in two majority-Latinx communities: one suburban (Marin) and one rural(Merced). In Aim 2, we will determine the population-level prevalence of active (PCR+) SARS-CoV-2 infection,most at-risk subgroups, and attitudes and preferences of community members regarding COVID-19 testingservices during baseline mass testing campaigns at the Marin and Merced sites. The campaigns will offertesting to all community residents regardless of symptoms at easily accessible venues, implemented inpartnership with each site's LTF. In Aim 3, we will conduct a 3-arm randomized controlled trial (RCT) todetermine the comparative effectiveness of two behavioral strategies - one that leverages incentives (extrinsicmotivation) and another that relies on altruism framing (intrinsic motivation) compared to standard offer ofretesting (control) - to increase frequent SARS-CoV-2 retesting among most at-risk sub-groups (identifiedduring Aim 2 campaigns) within the study communities. The proposed research will provide critical data toinform scalable testing strategies, reduce transmission, decrease health disparities, and set the stage forfuture, biomedical interventions, such as vaccines.",2020,2022,University Of California-San Francisco,3432455,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Diagnostics | Disease transmission dynamics | Impact/ effectiveness of control measures | Approaches to public health interventions | Community engagement | Policy research and interventions,2020 +C09533,1R42DE030832-01,A SARS-CoV-2 Breathalyzer for Direct Virus Detection,"Project SummaryA substantial and growing body of evidence has demonstrated that COVID-19 is transmitted by human-emittedairborne particles; therefore, it is critical to rapidly screen individuals to determine whether they are at risk oftransmitting the disease to others before they enter large venues (e.g., airports, schools) and smaller oneswhere extended exposure or close proximity is expected (e.g., dental offices, hair salons). Given the largenumber of asymptomatic cases of the disease, the infrared thermometers and health questionnaires frequentlyused to screen individuals are plainly inadequate. Existing SARS-CoV-2 detection technology is time consum-ing and complicated to use, expensive and not portable and therefore ill-suited to use as point of care (POC)screening tools. Tests recently approved by the FDA under the Emergency Use Authorization face some ofthe same challenges.The goal of this project is to develop and test a novel breathalyzer for detecting aerosolized SARS-CoV-2 di-rectly from exhaled breath in near real-time by marrying a proven, cutting-edge aerosol sampling technologywith a novel and inexpensive virus detector. The innovation is directly detecting virus in the breath, while otherbreathalyzers depend on indirect detection (VOCs and AI algorithms) to infer the presence of the virus.In this Fast-track STTR project, Aersol Devices Inc (ADev) will modify its commercial bioaerosol collector,which is used to sample from the ambient environment, to enable it to collect viruses from breath samples intoa concentrated liquid sample. The University of Minnesota (UMN) will modify its Magnetic Particle Spectrome-ter (MPS), a version of which has previously been used to detect Influenza A H1N1 virus, so that the liquidsamples from the collector can be analyzed to detect SARS-CoV-2.Specific aims include developing the hardware for transforming an ambient sampler into a breath sampler, de-signing a rapid means of decontaminating the collector between tests, integrating the collector and the detectorinto a robust package, functionalizing magnetic nanoparticles with SARS-CoV-2 antibodies, increasing the sig-nal/noise ratio of the MPS electronics, reducing the assay time, improving the analytical sensitivity/specificity,measuring the clinical sensitivity/specificity and comparing to RT-qPCR in pre-clinical testing.The technology platform proposed is flexible and extensible and could be tailored to detect other pathogens(e.g., rhinoviruses, respiratory syncytial virus, parainfluenza virus other coronaviruses, etc.). This flexibility isvaluable since (1) this will not be the last pandemic (new pathogens in the future) and (2) development couldpivot to a different pathogen if a vaccine or other control measures bring the current COVID-19 pandemic un-der control before this SARS-CoV-2 breathalyzer is commercially available.",2020,2021,Aerosol Devices Inc,254027,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09534,3R01HL151292-01S1,Determinants and Outcomes of Nicotine Metabolite Ratio in HIV + Smokers,"Project Summary COVID-19, the disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), hasled to a global pandemic and has exacerbated existing health inequities among vulnerable populations.Despite higher rates of COVID-19 in Black and Latinx individuals compared to White individuals, rates oftesting in predominately non-White, low-income communities are significantly lower than in high-income areas.Strategies to increase COVID-19 testing rates in underserved populations are thus urgently needed. Self-testing, where individuals collect their own samples, is now feasible for the detection of SARS-CoV-2.Self-testing can increase testing convenience and privacy and has been effectively leveraged to expand testingfor other infections, such as HIV, in key populations across a broad spectrum of contexts. However, self-testingmay be limited to those with access to health services, without reaching individuals underserved by existingmedical systems. One promising approach to increase test uptake is the secondary distribution of self-testingkits, where an individual distributes tests to contacts in their social network and encourages them to self-test. Asignificant advantage of a secondary distribution strategy is that by decentralizing a health care process,individuals may be more likely to access services if delivered by social network peers, rather than healthprofessionals. In addition, secondary distribution can enhance contact tracing efforts, as individuals diagnosedwith COVID-19 can distribute self-tests to close contacts to identify additional cases. Given high levels of COVID-19 misinformation, stigma, and medical mistrust among vulnerable populations, this peer-driven test distribution strategy holds significant promise in increasing the reach of COVID-19 testing among underservedpopulations. In collaboration with our community-based partner, Public Health Management Corporation, we willconduct a 1:1 randomized trial with 1048 individuals cared for at Federally Qualified Health Centers to evaluatewhether secondary distribution of SARS-CoV-2 self-tests increases test uptake compared with referrals amongunderserved populations in Philadelphia (Aim 1). We will also assess whether the secondary distribution ofself-tests to close contacts among individuals with COVID-19 facilitates case detection (Aim 2). Additionally,we will use a mixed methods strategy to identify key social, ethical, economic, and behavioral barriers andfacilitators to secondary distribution to inform its future modifications, implementation, and scale-up (Aim 3).We will engage our relationship with community partners to reach underserved individuals with housing instability, immigrants, and those with significant medical comorbidities including HIV, viral hepatitis, andsubstance use disorders, in order to increase COVID-19 test uptake in these populations. As more rapid anduser-friendly diagnostic tests emerge, this secondary distribution model may become even more impactful. Theproposed project may establish a new paradigm for expanding COVID-19 testing and contact tracing.",2020,2021,University Of Pennsylvania,1446525,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience","Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Community engagement",2020 +C09535,3UL1TR001876-05S1,Adding CTSI-CN COVID Data to the N3C,"PROJECT SUMMARYThis proposal requests a supplement to the parent NCATS award for the Clinical and Translational ScienceInstitute at Children's National (CTSI-CN), a partnership with George Washington University. The supplementis requested to aid our CTSI-CN informatics team and clinical investigators extract targeted data from theelectronic health records of patients who have been tested for SARS-CoV-2 as part of the COVID-19 pandemicat either of our two institutional hospital systems, namely, Children's National Hospital and George WashingtonUniversity Hospital. These data will then be deposited with the National COVID Cohort Collaborative (N3C)data enclave. We will then develop an approach for regular data transfers to keep the N3C data enclave up todate with important data from Washington DC from across the health lifespan.",2021,2021,Children'S Research Institute,99848,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Research on Capacity Strengthening,Institutional level capacity strengthening,2020 +C09536,3R41EB029284-01S1,A PORTABLE MULTI-MODAL OPTICO-IMPEDANCE SYTEM FOR EARLY WARNING OF PROGRESSION IN STABLE COVID-19 PATIENTS,"Project Summary / Abstract:COVID-19, the clinical presentation associated with SARS-CoV-2 infection, has already profoundly impactedhealthcare systems globally. Of particular note, communities such as long-term care facilities, assisted livingcommunities, and prisons, are being devastated because of their high density of vulnerable individuals.Nursing home residents, which represent only 0.5% of the US population, account for 25% of COVID-19deaths. Early detection of COVID-19 progression in these patients is critical to improving outcomes of patientswho are in an early stable condition but at risk of deteriorating, but must be balanced with efficient use ofprimary care resources and adequate protection of healthcare workers. An early alert to progression with ahigh sensitivity and an acceptable rate of false-negatives would save patient lives, reduce exposure ofhealthcare workers, and would also facilitate resource-shifting in the face of a surge. The time, money andeffort saved by allowing medical resources to be applied more accurately is the essence of precision medicine.During our current STTR efforts, we have developed and evaluated an opto-impedance system capable ofintegrating and classifying optical, electrical impedance spectroscopy and tomography data to detect changefrom baseline signatures of early ongoing hemorrhage with high accuracy. This proposal will (1) scale up ourhardware inventory, (2) deploy on COVID-positive patients to collect continuous multiplex data and (3) retrain our algorithms using the data to detect associated deterioration due to progression of COVID symptoms. Thismultivariate approach that has already been demonstrated in other pre-shock models, has the potential toprovide critical diagnostic and prognostic feedback in high-risk individuals.",2021,2022,Multivariate Systems Inc,155282,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +C09537,3U01AI063594-17S1,Multiparametric mapping of Covid-19 immune responses in Kidney transplant recipients,"AbstractAs of May 2020, over five million confirmed cases of COVID-19 have been reported globally with over 400,000associated deaths. Around 5-20% of patients develop critical illness, which predominantly manifests as acuterespiratory distress syndrome. When this develops, the estimated mortality is around 40%, and as high as 80%in ventilated patients. Several early reports describe the development of an excessive inflammatory response,the so-called `cytokine storm', which is strongly associated with rapid deterioration in clinical condition andmortality.Early reports of kidney transplant recipients, who are at high risk due to chronic immunosuppression andadditional comorbid diseases, portray a concerning picture. In one series of 36 patients, 39% requiredmechanical ventilation, 21% required renal replacement therapy, and 28% died. Of the 11 patients that wereintubated, 64% died. However, there is still an unmet need of understanding disease natural course, specificrisk factors, identifying biomarkers, as well as potential impact of COVID-19 on graft/patient survival invulnerable KTRs. To fill this information gap, we propose a comprehensive observational analysis of epidemiological factors and immunological assay results in COVID19-infected KTRs at 2 medical centers atthe epicenter of COVID19 infection in NYC (Mount Sinai Hospital in Manhattan and Montefiore Hospital in theBronx). We hypothesize that specific recipient clinical characteristics affect COVID-19 clinical courseand that recipient immunosuppression in KTRs alters the ability of COVID-19 KTRs to developprotective anti-COVID-19 humoral and cell-mediated immunity that contributes to the morbidity andmortality of these individuals.We will test this hypothesis by 1) examining risk factors of COVID-19 severity in a large dataset of KTRs andindividuals from the general population with COVID-19 (aim 1); 2) by characterizing the COVID-19 reactivehumoral and cellular immune response in serially collected samples from COVID-19 KTRs (aim 2); and 3) bycomprehensive assessment of DNA and serial serum, RNA, and PBMC from COVID-19 KTRs to identifydisease mechanisms and potentially informative biomarkers for outcomes (aim 3).The proposed work is significant because of the high incidence of the disease, rate of community transmission,high mortality, and absence of clearly effective therapeutic options. Our studies will be amongst the first todefine risk factors, predictors, and pathogenic mechanisms of COVID-19 in Kidney transplantation and mayapply to recipients of other transplanted organs, as well as to individuals on chronic immunosuppression due toautoimmune diseases.",2020,2021,Icahn School Of Medicine At Mount Sinai,598676,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C09538,3R01DC017174-02S1,"Defining Trajectories of Linguistic, Cognitive-Communicative and Quality of Life Outcomes in Aphasia","Stroke imposes significant burdens on the health and quality of life terms of healthcare costs and lost productivity.Aphasia adds to the cost of stroke related care. Many stroke survivors with aphasia receive therapy in inpatientrehabilitation facilities. However, aphasia recovery is variable and there is limited evidence on the benefits ofinpatient rehabilitation on outcomes. The objective of the parent R01 is to describe the trajectories of linguistic,cognitive-communicative, and health-related quality of life outcomes following stroke in persons with aphasiaduring inpatient and outpatient rehabilitation to 18 months following stroke. A sample of 300 consecutively-admitted stroke patients with aphasia recruited at three Midwestern rehabilitation hospitals will completemeasures of linguistic and cognitive-communicative performance, and the Quality of Life in NeurologicalDisorders Measurement System instruments during rehabilitation and at 6-,12-, and 18- months post-stroke. Wewill model outcomes as individual and group trajectories, allowing us to develop individual predictions whichcould inform clinical planning and decision-making for new patients.The Covid-19 pandemic has resulted in drastic changes in therapy access and utilization since we launched thisstudy. As a result, patients with aphasia may not receive any inpatient or outpatient speech and language therapy,their lengths of stay or therapy schedules may be shortened, or therapies may be offered only throughtelerehabilitation. Thus, the Specific Aims of this supplement are to: 1. Characterize the Covid-19 experience and telerehabilitation access, service delivery experiences, and perceived effectiveness in a large national cohort of adults with aphasia. 2. Describe the nature and extent of disparities in telerehabilitation service delivery related to sex, race, ethnicity, age, and insurance coverage. 3. Compare the cognitive-communicative and psychosocial health outcomes at 6, 12 and 18 months post- stroke achieved by patients in our longitudinal cohort study (R01 DC017174) receiving telerehabilitation vs. in-person vs. no services following discharge from inpatient rehabilitation.We request a supplement for two years, given the longitudinal nature of the parent R01 grant. At the end of thesupplement, results for Aims 1 and 2 will be available. Descriptive results will be available for Aim 3 on a cohortof about 50 participants followed to 18 months post-stroke, which will be sufficient to allow for a proof of conceptdescriptive analysis, and eventual 300 by the end of the parent R01 for a complete analysis.This supplement demonstrates innovation in that SLP telerehabilitation is relatively new. Outside of controlledresearch studies, its benefits and limitations have not been assessed. An improved understanding of aphasiarecovery may assist with prognosis, allowing patients and caregivers to plan, helping clinicians chooseappropriate therapies, providing benchmarks against which to measure change, and allowing therapymodifications when patients do not attain benchmarks.",2020,2024,Rehabilitation Institute Of Chicago D/B/A Shirley Ryan Abilitylab,177886,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Other secondary impacts | Health service delivery,2019 +C09539,3U01HL152401-02S2,Washington Entrepreneurial Research Evaluation and Commercialization Hub,"The overarching goal of the partnership between NIH and the University of Washington (UW) EntrepreneurialCenter for Research Evaluation and Commercialization Hub (referred to as WE-REACH) is to facilitate andaccelerate the transformation of health research innovations into products. This NIH funded WE-REACHCenter is a National Center of REACH in the Northwest region. Two key objectives of the Center are to (1)assist investigators with innovative technologies to establish proof-of-product concept definition (2) facilitating the formation of spinout companies on track to a self-sustaining structure. With well-established expertise,know-how and infrastructure to assist the Research and Development of the following two Covid-19 technical-ready Covid-19 research and develop projects intended to verify proof-of-product concepts with workingprototype.(1) Aptamer-based highly sensitive biosensors for salivary COVID-19 antigen detection (Pun)(2) Broad-spectrum detection of VOC and non-VOC biomarkers from patient exhalant using biomimeticmultiplexed eNose biosensor for COVID-19 diagnosis (Saikaya)The two technically sound approaches employ by the point-of-care device candidates intend to detect viralantigen in saliva and exhalant biomarker signatures from infected subjects without having to send sample to acentralized facility or a long wait-time for results. WE-REACH will assist the investigators in developingmilestone-driven, stage-gated, activity-based project planning and tracking to accelerate proof-of-productconcept studies within 2-year of funding. The study results will provide measurable outcomes that are deemedsufficient for upscaling and appropriate for follow-on funding.",2020,2021,University Of Washington,412300,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09540,3R01EB025854-03S1,SpongeBot: genetically engineered cells to suppress SARS-CoV-2 and future viruses,"SpongeBot represents a new class of genetically modified cells to address the COVID-19 pandemic, leveraginga novel antiviral platform developed under the proposer team's existing NIH NIBIB R01 project. This antiviral platform facilitates rapid, targeted SpongeBot development and deployment against SARS-CoV-2, its viral mutations, as well as entirely new viruses - providing a barrier to future viral pandemics.SARS-CoV-2 is highly communicable and individuals can transmit the disease even prior to becomingsymptomatic, sharply increasing the rate of disease spread. During the first two weeks following infection, theinnate immune system attempts to slow down the rapidly multiplying pathogen to provide time for the adaptive immune system to develop more specific and effective mechanisms to destroy the virus. However, in individuals with decreased or compromised immune responses, the excessive viral load can lead to elevated inflammation,severe tissue damage, and ultimately death.SpongeBot, our bioengineered cell-based therapy solution, provides vital support to the body's immune system,through its genetically designed ability to sequester and destroy SARS-CoV-2 viral particles at sites of injury, inaddition to attenuation of the immune system's hyperinflammatory response to the virus. Administering SpongeBot cells to an infected individual reduces and keeps viral load below dangerous thresholds, prevents harmful hyperinflammation, and provides the adaptive immune system the time required to mount an effectivedefense against the virus.SpongeBot can be administered prophylactically to at-risk populations (e.g., healthcare workers, the elderly, orimmunocompromised individuals), or therapeutically at any stage during the course of viral infection. Importantly, SpongeBot therapy is extremely safe; the base technology has a long proven clinical safety track record. Unlike the lengthy development times necessary for vaccines or antiviral medications, a targeted SpongeBot therapy against a predicted virus can be placed in clinical trials immediately. SpongeBot development for a novel viruswould be ready for deployment in only about 12 weeks.",2020,2021,Massachusetts Institute Of Technology,752435,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",,2020 +C09541,1U18TR003775-01,"Effective, Reagent-free Detection of the Odor Signature of Covid-19 Infection Using a Nano-Enabled Sensor Array","PROJECT SUMMARYCOVID-19 presents a public health emergency: There is a critical need for rapid, not reagent intensive, non-invasive testing technologies. This program will lead to the production of a prototype system to diagnoseCOVID-19 infection using the body odor signature of the disease. Our goal is to maximize societal impactby creating a validated prototype that can be used in a community or workplace setting by minimallytrained personnel for low-cost, on-the-spot diagnosis within minutes. The system will be developed in amanner that puts it on a pathway for rapid FDA approval. The Research Aims are:Aim 1. Optimization, assembly, and integration of a prototype system with the ability to odor signatureof COVID-19 in samples of body odor. The system will be simple to use, pose essentially zero risk to theoperator and the test subject, and report a result within minutes. The production cost at scale will beapproximately $9,000 for the complete measurement system, with a per test cost of approximately $0.50. Thedesign and construction of the prototype will be conducted by Novo Engineering, a leading firm with extensiveexperience in medical device development.Aim 2. Software development. Software for the system from VOC sampling to final diagnostic result will bedeveloped to ensure error-free operation of the device. Our preliminary results suggest that simple lineardiscriminant analysis (LDA) does an excellent job of classifying VOCs from human body odor as COVID-19positive or negative (92% sensitivity and 87% specificity). Optimization of the sensor array (Aim 1) and use ofricher feature sets in our classifier models will lead to further performance improvements in the prototype system.Aim 3. System Benchmarking and Validation. We will benchmark the full prototype system against a numberof VOC mixtures, with and without in vitro skin models. The system will undergo extensive testing against bodyodor samples from individuals with pathological conditions other than COVID-19 and other sources of potentiallyconfounding VOCs. The prototype will be validated against 1000 samples drawn from the COVID-SAFE programat Penn. The screening will include all members of the Penn community, and represents incredible racial andethnic diversity as well as a wide variance in age, sex, and gender.Aim 4. Regulatory Approval Plan The plan will be developed under the direction of Sr/Key personnel JohnFuson, JD, an attorney at Crowell & Moring LLP and a former Associate Chief Counsel at FDA. Novo Engineeringhas extensive experience in guiding prototype design in alignment with the requirements for FDA approval. Theproposed COVID-19 VOC-based testing device will be regulated by the FDA, likely as a Class I or II medicaldevice. Because there is no clear predicate device to reference in this case, we intend to submit a direct de novopetition to FDA asking the agency to categorize and clear the proposed COVID-19 testing device as Class I orClass II without reference to any predicate.",2020,2022,University Of Pennsylvania,999830,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09542,1U01DA053903-01,Wastewater Assessment for Coronavirus in Kentucky: Implementing Enhanced Surveillance Technology,"Wastewater Assessment for Coronavirus in Kentucky - Implementing Enhanced SurveillanceTechnologySurveillance for SARS-CoV-2 is hindered by the availability of testing, particularly in remote and ruralareas. Screening of wastewater for SARS-CoV-2 viral biomarkers offers a viable alternative to individualtesting and it can identify communities and facilities that are at risk of becoming hotspots.Wastewatersurveillance overcomes several limitations of clinical surveillance, such as the need for robust healthcareand laboratory infrastructure and the lack of representative and comprehensive testing withincommunities. Conventional wastewater surveillance takes samples from sewer systems or wastewatertreatment facilities and uses a series of extraction steps prior to advanced PCR technology to quantitatethe viral biomarker (RNA). This approach is time and resource-intensive, which limits its wide-scaleapplication. Developing next generation technology to simplify wastewater RNA extraction andquantitation will make it feasible to use more broadly at facilities and in rural communities. The limitedclinical testing for COVID-19 in rural Southeastern Kentucky hampers disease surveillance and preventsinformed public action to mitigate and contain the spread of disease. Wastewater testing for SARS-CoV-2 in these communities using field-friendly technology will provide important information to localauthorities and citizens about the spread and trend of SARS-CoV-2 infection in their communities. Ourproject will accomplish two aims: 1) Develop next generation wastewater assessment technology and 2)Implement and evaluate the next generation wastewater assay. For Aim 1 we adapt technology inventedby our team termed exclusion-based sample preparation (ESP) to simplify and improve RNA extractionfrom wastewater. We will pair ESP with loop-mediated isothermal amplification (LAMP) technology forRNA detection to create a sensitive, robust, and field-friendly platform for testing wastewater for SARS-CoV-2 RNA. We will compare the next generation assay with established techniques on metrics ofsensitivity, specificity, and usability (e.g., assay time, number of assay steps). For Aim 2 we will firstvalidate the next generation assay in the field at congregate living facilities in a side-by-side comparisonwith conventional wastewater surveillance. Next, building on existing relationships in AppalachianKentucky, we will recruit and train a purposive group of wastewater treatment plant operators, watershedwatch citizen scientists, and school science teachers to test wastewater in their communities and schoolsusing the field-friendly next generation wastewater assay. Field results will be validated in the lab. Arobust mixed methods evaluation using the RE-AIM framework will assess community perceptions offeasibility, acceptability, and utility of wastewater surveillance for SARS-CoV-2 and identify communitymeasures taken in response to test results.",2020,2022,University Of Kentucky,1834258,Environment,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Epidemiological studies,Disease surveillance & mapping,2021 +C09543,3UM1AI069511-14S1,University of Rochester HIV/AIDS Clinical Trials Unit,"The University of Rochester (UR) Clinical Microbiology laboratory is a CLIA-certified laboratory that offers bacteriology (ID and susceptibility), immunology, mycobacteriology, mycology, parasitology, serology, TB and virology testing including specialized antibiotic and antifungal studies. The laboratory evaluates and adds infectious diseases molecular diagnostic tests on an ongoing basis and has sufficient capability for SARS-CoV-2 RNA testing to meet current clinical demands.",2020,2020,University Of Rochester,290519,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09544,1S10AI162135-01,PPE Request,"PROJECT SUMMARY / ABSTRACTTo meet the challenge of the COVID-19 pandemic, Boston Children's Hospital (BCH) requested and received an administrative supplement to NIAID grant U19AI118608 ""Ontogeny of Human Vaccine Responses"" to fundthe Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) Clinical and Data Coordinating Center(CDCC). The IMPACC study is an observational cohort collecting detailed clinical, laboratory, and radiographicdata in coordination with biologic sampling of blood and respiratory secretions and viral shedding in nasalsecretions in order to identify immunophenotypic and genomic features of COVID-19-related susceptibilityand/or progression in order to generate hypotheses for effective host-directed therapeutic interventions, to helpto prioritize proposals for such interventions, and/or optimize timing for administration of host-responsedirected therapeutics.Many sites in the IMPACC study lacked sufficient PPE to protect all study site staff interacting with hospitalizedCOVID-19 patients. Therefore, the IMPACC CDCC sought additional resources to distribute to the participatingsites. RhoFED responded to this need by procuring the necessary additional PPE, which consisted of masks,masks with eye shields, gowns, gloves, and face shields.",2021,2022,Rho Federal Systems Division Inc,373601,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2021 +C09545,3R01EB023910-04S1,Pulsed Focused Ultrasound (pFUS) exposures and devices for tissue permeabilization without contrast agents,"PROJECT SUMMARYAccording to recent reports from across the world, the need to continuously evaluate lung edema in critically illCOVID-19 patients is essential. Chest x-ray has reduced sensitivity early in the disease; the contagiousness ofthe virus and the risk of transporting unstable patients with hypoxemia make chest CT a limited option for thepatient with suspected or established COVID-19. Lung ultrasound (LUS) is non-ionizing and safe, and hasrecently emerged as a useful triage and monitoring tool for lung edema quantification in COVID-19 patients. InLUS, imaging artifacts termed A-lines (periodic horizontal lines parallel to the lung surface indicating a normalaeration pattern) and B-lines (comet-like hyperechoic regions indicating an alveolar or interstitial abnormality)are evaluated. B-lines stem from acoustic reverberations within regions of alveolar edema, and their number andthickness are known to be correlated with edema severity. However, visualization and quantification of B-linesrequires substantial training, and even then, are highly operator and machine dependent. This is in part due toa still incomplete understanding of the exact physical mechanism of B-line formation. In this emergencycompetitive revision to the current award on ultrasound cavitation-aided drug delivery to solid tumors we proposeto build on our expertise in dissecting the origins of US imaging artifacts and ultrasound instrumentationcapabilities to 1) identify the origins of B-line artifact in LUS and specific associated RF signal features, and 2)based on the attained understanding, develop a single-element, wearable, automated, non-imaging lungultrasound sensor (LUSS) for continuous monitoring of lung pathology while minimizing provider time, risk ofvirus exposure, and radiation. Individual adhesive LUSS elements will be attached to patients in specificanatomic locations similarly to ECG leads, and ultrasound signals will be collected and processed withautomated algorithms to provide lung edema score that can be used in clinical decision making. We havedesigned a proof of principle study scaled to the shortest timeline possible to get the device into the clinic quickly,with the following specific aims. In SA1 we will perform standard LUS exams in non-COVID patients withcardiogenic pulmonary edema while collecting raw RF signal data to understand the manifestation of B-lines inraw RF signals and develop automated signal processing algorithm. In SA2 we will design and fabricate single-element LUSS prototype and validate the automated signal processing algorithm against LUS imaging in lung-mimicking sponge-based phantom. By the end of the 9-month project the prototype device will be ready for usein not only COVID19 patients, but other ED patients for whom continuous evaluation of lung condition is essential(bacterial pneumonia, cardiogenic edema, dialysis). Our commercialization approach here is to broadly licensethis simple technology so that large ultrasound manufacturers with broad sales and distribution capabilities canget the technology to the users.",2021,2021,University Of Washington,306746,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C09546,1R42DE030829-01,A multimodal platform for Oral screening of COVID-19,"The development of a rapid and reliable sensor system from readily available oral specimens is crucial forthe screening and management of SARS-CoV-2 infection. Other than tests that require laboratory-scaleinstrumentation, the development of rapid tests can play a timely role in the management of an outbreak.Current rapid tests often involve the antibodies in a lateral flow format to detect viral protein componentsand, depending on the implementation, can result in a relatively high degree of error. In partnership withMIT, InnoTech proposes the development of a multiplexed sensor platform based on nanomaterials capableof molecular binding and subsequent reporting. We will develop and commercialize a multiplexed sensorplatform using nanomaterial reporters capable of rapid simultaneous detection of multiple components ofviral particles in a field applicable electrochemical device. For our Phase I- Aim 1 we will focus on thedevelopment and optimization of synthetic biosensors for accurate detection of SARS-CoV-2 viral proteinsand nucleic acid. Our milestone is the discovery and validation an array of molecular recognition biosensorsagainst both protein and nucleic acid segments of SARS-CoV-2. We will complete this phase in 4 months.In Phase II-Aim 1, we will develop and validate the electrochemical detectors. We will utilize the syntheticbiosensors identified and validated in Aim 1 to an electrochemical platform for the rapid detection of anactive SARS-CoV-2 infection using multiple biomarkers of the infection. We will specifically employcommercially-available, disposable electrode platforms and existing potentiostats from Metrohm DropSensto streamline scale-up and commercialization. Our milestone, to be completed in year 1 of Phase II, is tohave a multiplex biosensor chip and an alpha prototype with a multiplex biosensor chip and a potentiostatreader which we will benchmark for sensitivity and quantitative accuracy against existing COVID-19diagnostics. In Phase II-Aim 2, we will validate the prototype chips and detectors with retrospective clinicalspecimens in preparation for EUA-FDA submission. We will determine the LOD, clinical performance,and cross-reactivity with other respiratory pathogens and normal flora. The milestone for this Aim is todocument a multiplex of at least two proteins and two nucleic acid biosensors for SARS-CoV-2 that willprovide a LOD of 5-20 viruses per microliter in an oral specimen and will be clinically validated withgreater than 95% concordance with RT-PCR in 30 positive and 30 negative specimens.",2020,2021,Innotech Llc,255999,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09547,3U54MD007592-27S1,Implementing Community-based Approaches to Increase SARS-CoV-2 Testing among an Underserved and Vulnerable Hispanic Population,"PROJECT ABSTRACTHispanics living in the United States have been negatively affected by the COVID-19 pandemic in adisproportionate manner, including significantly higher infection and hospitalization rates compared with non-Hispanic whites. The El Paso, TX metropolitan area has a substantial Hispanic population that has beenprofoundly affected by the current SARS-CoV-2 pandemic, especially the vulnerable residents of rural El PasoCounty. Many of these residents suffer from marked cumulative disadvantages with limited healthcare, pooraccess to public transportation, work as essential workers in low-paying frontline jobs, and demonstrate apersistent hesitancy to interact with unfamiliar medical systems and processes, resulting in ""SARS-CoV-2 testingdeserts"". There is a critical need to increase the number of individuals being tested for SARS-CoV-2 in El PasoCounty, however, success in this space requires an integrated and personalized approach whereby residentsare engaged with and informed by trusted co-ethnics and local organizations. The proposed aims will strategicallyintegrate University of Texas at El Paso (UTEP), non-profit, business, and public partners, coupled with culturally-centric familial and Community Health Worker (CHWs) networks, as catalysts to: 1) reduce testing deficiencies byproviding SARS-CoV-2 testing information, navigation strategies to testing sites, and implementing local pop-uptesting sites, and 2) provide foundational data for understanding testing barriers and developing platforms forassessing future COVID-19 vaccine uptake willingness for El Paso residents. The UTEP Border BiomedicalResearch Center (BBRC), and associated Coronavirus Testing Program that provides CLIA-certified testing, iscentral to completion of the integrated approaches, and the established capability of the investigative team tointeract with community partners and recruit participants is a prominent strength of the proposed plan. Theproposed studies will test the novel hypothesis that improving the reach, acceptance, uptake and sustainabilityof SARS-CoV-2 testing for the most marginalized populations of El Paso County is dependent on implementingstrategies that target the cultural, social and behavioral factors characteristic of this population. The multifacetedapproach will enhance the testing capacity in the El Paso region, reduce testing hesitancy, increase coronavirustesting numbers for vulnerable populations within specific testing deserts, and exert a sustained influence on thehealth status of the region by integrating the extensive collaborative networks that are essential for addressingthe persistent negative social determinants of health.",2020,2022,University Of Texas El Paso,690902,Human Populations,Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,1998 +C09548,3U54GM104940-05S3,Louisiana Clinical and Translational Science Center,"Project Summary/AbstractIn the US, COVID-19 has unveiled a disproportionate health burden in low income and underserved segmentsof society. In Louisiana, some of the greatest health and economic consequences are evident in our Blackcommunities. There is an urgent need to establish effective testing strategies in these communities as theFall/Winter virus surges unfold. The Louisiana Clinical and Translational Science (LA CaTS) Center providesthe essential infrastructure and key foundational support for biomedical research in our region and is uniquelypositioned to lead a community-engaged testing research project to determine differences in COVID-19 testingrates between community-based (churches, community centers, and schools) and medical clinic-based testingsites, and determine approaches that will increase uptake of testing in underserved Black communities in theSouth. We plan to address these issues using a two-pronged approach. First, we will use a community basedparticipatory research approach to determine differences in SARS-CoV-2 testing rates across distincttypes of test sites within five urban underserved Black communities in the American South. We will usea multimedia campaign to promote and conduct RT-PCR testing on salivary samples obtained from 2,000adults at 1) medical clinics, 2) schools, 3) community centers, and 4) churches (in random order) within fiveZIP codes with known low socioeconomic status (SES) and a high representation of Black residents. Theprimary outcome will be the number of tests performed at each type of test site. We will collect information onage, sex, race, BMI, employment, social determinants of health using an aggregate SES score to identifyimportant correlates of testing rates. Second, we will further leverage our strong and well-integratedpartnership with the Baton Rouge Mayor's Healthy City Initiative together with our LA CaTS CommunityAdvisory Boards (CABs) to conduct community-based focus groups to obtain qualitative data about theperceptions and attitudes related to testing access and potential barriers affecting such. We will use thisinformation to determine community-driven approaches that are effective in reducing barriers and createstrategies to increase SARS-CoV-2 testing uptake in urban underserved Black communities. Results ofthis project will greatly increase our understanding of the factors that have led to a disproportionate COVID-19health burden in these underserved populations and lay the groundwork for developing strategies to reducethese disparities in all underserved Black communities. Resulting data will inform the equitable deployment offuture virus/flu testing and a SARS-CoV-2 vaccine.",2020,2022,Lsu Pennington Biomedical Research Ctr,961973,Human Populations,Black,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C09549,1R61HD105619-01,COVID-19 Network of Networks Expanding Clinical and Translational approaches to Predict Severe Illness in Children (CONNECT to Predict SIck Children),"The SARS-CoV-2 pandemic has manifested in children with a wide spectrum of clinical presentations rangingfrom asymptomatic infection to devastating acute respiratory symptoms, appendicitis (often with rupture), andMultisystem Inflammatory Syndrome in Children (MIS-C), a serious inflammatory condition presenting severalweeks after exposure to or infection with the virus. These presentations overlap in their clinical severity whilemaintaining distinct clinical profiles. Public health and clinical approaches will benefit from an improvedunderstanding of the spectrum of illness associated with SARS CoV-2 and from the capacity to integrate data toachieve two goals: (i) to identify the clinical, social, and biological variables that predict severe COVID-19 andMIS-C, and (ii) to target those populations and individuals at greatest risk for harm from the virus. We proposethe COVID-19 Network of Networks Expanding Clinical and Translational approaches to Predict Severe Illnessin Children (CONNECT to Predict SIck Children) comprising eight partners providing access to data on >15million children. Our network will systematically integrate social, epidemiological, genetic, immunological, andcomputational approaches to identify both population- and individual-level risk factors for severe illness. Ourunderlying hypothesis is that a combination of multidimensional data - clinical, sociodemographic, epidemiologic,and biological -- can be integrated to predict which children are at greatest risk to have severe consequencesfrom SARS-CoV-2 infection. To test our hypothesis, we will develop CONNECT to Predict SIck Children, anetwork of networks that leverages inpatient, outpatient, community, and epidemiological data resources tosupport the analysis of large data using machine learning and model-based analyses. For the R61 phase, wewill develop and refine predictive models using data from our network of networks (Aim 1). We will also recruitparticipants previously diagnosed with either COVID-19 or MIS-C (along with appropriate controls who have hadmild or asymptomatic infections with SARS-CoV2), who will provide survey data (including social determinants)and saliva and blood samples to identify persisting biological factors associated with severe disease (Aim 2). Wewill iteratively assess our models using a knowledge management framework that considers the marginal valueof data for improving models' predictive capacity over time. In the R33 phase, we will validate and further refinepredictive models incorporating data from additional participants recruited throughout our network of networks,including newly infected children with severe COVID-19 or MIS-C identified through real-time surveillance (Aim3). We seek to develop predictive models for children and adolescents that are useful, sensitive to communityand environmental contexts, and informed by the REASSURED framework specified by the RFA. The modelsand biomarkers developed through our nationwide network of networks will produce generalizable knowledgethat will improve our ability to predict which children are at greatest risk for severe complications of SARS-CoV-2 infection. This knowledge will facilitate interventions to prevent and treat severe pediatric illness.",2020,2022,Rutgers The State University of New Jersey,840235,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2021 +C09550,3R01CA235773-02S1,Expanding population-level interventions to help more low-income smokers quit,"ABSTRACTMany low-income Americans, racial and ethnic minorities, and other marginalized groups live in information-poor environments, disproportionately exposed to misinformation about COVID-19, and distrusting medical,government and scientific institutions and leaders. These and other social, cultural and behavioral factors posesignificant obstacles to public health efforts to increase population testing and vaccination in a pandemic.Effective health communication is urgently needed to help counter these challenges and reduce disparities inCOVID-19's impact. Working in close partnership with 2-1-1 helplines in four states and nationwide, wepropose rapid-cycle research that moves from audience analysis to message testing among prioritypopulations identified in the NOSI. Our approach builds on strong evidence from our team's decades-longprogram of health communication research to eliminate disparities, especially proven message tactics such ascultural values, disparity framing, and narratives, that will be applied to the COVID-19 context. Specifically, wewill conduct a multi-method content analysis of 43,000+ COVID-19 testing inquiries to 2-1-1 (Aim 1), surveyand interview 350 2-1-1 callers and phone operators (Aim 2), and develop and evaluate in randomized A-Btesting new COVID-19 testing messages among 300 2-1-1 callers (Aim 3). Taken together, these activities willidentify essential context and content for communicating about COVID-19 testing to vulnerable populations,integrate this knowledge into proven message tactics, and determine their impact on interest in and intention tobe tested and other key outcomes. Our partnership with 2-1-1s is central to the proposed research. Of the 24priority populations identified in the NOSI, 2-1-1s serve a higher proportion of callers from nearly every groupcompared to their proportion of the U.S. population, including 60-80% racial or ethnic minorities, 40-55% withhousehold income below $10,000, and 1 in 4 not completing high school. During COVID-19, 2-1-1s in 36states have fielded 964,286 COVID-19 requests. These first-hand accounts from underserved Americansconcerned about or affected by COVID-19 must inform communication efforts, and the infrastructure of 2-1-1 iswell suited to support rapid testing of promising approaches.",2020,2024,Washington University,518613,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2019 +C09552,3R01MD012767-04S1,Building Resilience and Vital Equity (BRAVE) - Increasing COVID-19 Testing in American Indians,"AbstractThe COVID19 pandemic continues to hit hardest on underserved communities including American Indians(AI)/Alaska Natives (AN). Diseases with significant health disparities and social determinants of health aremajor risk factors and define COVID19 related disparities among AI/AN. Increased testing and upcomingadherence to vaccination recommendations are two important strategies to manage COVID19 and mitigate theimpact of the virus on marginalized communities. Mounting evidence indicates that underserved communitiesare less likely to actively participate in mass testing and immunization recommendations due to poverty,access, inadequate information, logistics and issues surrounding fear, stigma and trust. North Carolina (NC)has the largest AI population east of the Mississippi River and the sixth largest AI population in the nation withmore than half living in rural underserved counties of Robeson, Scotland, Hoke and Cumberland. Thisproposal is a partnership between two community engaged academic institutions (North Carolina CentralUniversity - NCCU and University of North Carolina at Pembroke-UNCP) and a major community partner - TheLumbee Tribe of North Carolina (LTNC) with 62,500 members. We hypothesize that a bidirectional community-engaged approach to understand the social ethical and behavioral implications (SEBI) combined with focusedinterventions to address the barriers will increase testing and mitigate the consequences of COVID-19 in AIcommunities of NC. The specific aims of the proposal are (1) To understand the barriers and socialimplications of COVID19 testing among American Indians by designing and implementing culturally sensitivesurvey tools and intervention materials. (2) Implement BRAVE outreach and testing interventions to increasetesting in American Indian community and (3) Data analysis, evaluation and data sharing. BRAVE is a boldcommunity-engaged initiative to increase testing by addressing disparities and building resiliency to change thenarrative from struggle to strength in AI community as we fight this unfortunate public health emergency.",2020,2022,North Carolina Central University,1390688,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2017 +C09553,3U54EB027690-02S1,Emergency COVID-19 supplement for Atlanta Center for Microsystems Engineered Point-of-Care Technoloites (ACME POCT),"The advent of point-of-care (POC) diagnostic capabilities has enabled rapid and timely clinical evaluation in the physician's office, an ambulance, the home, the field, or in the hospital and has the potential to significantly impact health care delivery. In cardiology, pulmonology/critical care, and hematology, POC testing plays an especially significant role as the heart and lungs are among the most vital of organs necessitating real time diagnosis and rapid management during critical illnesses, while pathologic alternations in blood are associated with critical, systemic illness. One class of novel medical technologies that is showing promise for POC applications are microsystems-engineered technologies, that is, microchip-enabled devices ranging from microelectromechanical systems (MEMs)-based sensors, microfluidics, to even smartphone-based systems. Notable for their small size and power requirements, microchip-based systems provide the portability that is vital for POC testing. In addition, the capability of microsystems to convert sound and movement into electrical signals enable these technologies to be ideal devices to sense the dynamics of the lungs and heart and therefore to diagnose and monitor pulmonary and cardiac disorders. Moreover, microsystems engineering has brought forth the field of microfluidics, which is steadily finding applications for blood-based diagnostics, and therefore, hematologic applications. To that end, per the NHLBI's U54 POCTRN guidelines, the overall goal of the Atlanta Center for Microsystems Engineered POC Technologies (ACME POCT) is to assist and enable inventors from across the country who have developed microsystems-based POC technologies for cardiac, pulmonary, hematologic and sleep applications that are beyond proof-of-concept to define their specific clinical needs, conduct clinical validation, and refine their technology, with the objective of accelerating the path to translation and clinical adoption and directly addressing the barriers thereof. The ACME POCT uniquely leverages Atlanta's nationally top-ranked clinical programs at Emory University's hospitals and Children's Healthcare of Atlanta, one of the nation's largest pediatric hospital systems, as well the internationally acclaimed microsystems engineering expertise at Georgia Tech, which includes the Institute for Electronics and Nanotechnology (IEN), and other one-of-a-kind medical device prototyping, innovation, and testbed facilities. The ACME POCT PI's uniquely balance the engineering and clinical sides of the Center and comprise Wilbur Lam, MD, PhD, a clinical hematologist at Emory and Georgia Tech bioengineer with expertise in POC diagnostic development and commercialization, Oliver Brand, PhD, a renowned microsystems engineer and head of Georgia Tech's IEN, and Greg Martin, MD, MSc, a clinical pulmonologist at Emory and head of clinical research in Atlanta's NIH-funded CTSA. Importantly, the leadership of the ACME POCT has a history of collaboration and track record in managing Centers that have fostered medical device development.",2020,2021,Emory University,31080737,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +C09554,1R21AI159246-01,GS-441524 is Pharmacodynamically Equivalent to Remdesivir and Pharmacokinetically Superior Drug for the Treatment of COVID-19,"ABSTRACT. Covid-19 is a once in a generation epidemic that has had dire, destabilizing impacts across theworld. While remdesivir has emerged as the only drug with proven efficacy, its widespread distribution has beenplagued by supply-shortages. Careful review of pre-clinical data evidence that these problems largely derivefrom the poorly optimized phosphate pro-drug moieties on remdesivir, which ultimately make manufacturingremdesivir more difficult. Careful review of the literature indicates that, its parent nucleoside, GS-441524, is likelythe more optimal Covid-19 drug. We hypothesize that GS-441524 is pharmacodynamically equivalent drug toremdesivir, in its ability to generate active nucleotide triphosphate to inhibit the SARS-CoV-2 RNA polymerase.In addition to GS-441524 being significantly easier to synthesize, we contend that its direct administration would enable homogenous tissue distribution of active nucleotide triphosphate inhibitor compared to remdesivir; higherlevels of inhibitor would ultimately be achieved in lung epithelial cells most afflicted by SARS-CoV-2.This proposal will make fundamental biochemical advances at the in vitro level and therapeutic advancementsat the in vivo level. We will compare the rates bioactivation of GS-4441524 and remdesivir across a broad panelof primary human cell types and delineate the exact molecular mechanism and enzymes which bio-transformremdesivir and GS-441524 into the active triphosphate species. At the same time, we will establishpharmacodynamic equivalence between GS-441524 and remdesivir in mice and non-human primates. Finally,we will demonstrate that GS-441524 is ultimately superior to remdesivir in vivo for generating active triphosphateinhibitor, when each is administered at their maximum tolerated doses. Should our hypotheses prove correct,these data will support GS-441524 for IND and clinical trials.",2020,2022,The University of Texas MD Anderson Cancer Center,442002,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C09555,3R01NR018463-01A1S1,Alive Church Network: Increasing COVID-19 Testing in Chicago's African American Testing Deserts,"ABSTRACTThe epidemic of novel coronavirus disease 2019 (COVID-19) has caused an unprecedented public health crisisin the United States. African Americans (AA) have been disproportionately impacted, as systemic inequities havecontributed to increased exposure and vulnerability to COVID-19. Evidence suggests that AAs are delayingtesting and care for COVID-19, which increases risk of transmission and poor outcomes. In Chicago, segregatedAA neighborhoods have experienced some of the highest COVID-19 mortality rates in the city, yet large portionsof these neighborhoods remain testing deserts. Providing trusted, accessible, community-based testing inunderserved AA communities is critical to ensuring that AAs receive an early diagnosis, thereby reducing therisk of further transmission and improving clinical outcomes. This study leverages the Alive Church Network(ACN), a long-standing, community-driven coalition of African American pastors and public health researchersthat was developed as a sustainable infrastructure to address health inequities in chronic disease in segregatedAA neighborhoods in Chicago. The ACN was designed to address lack of access to health care, culturalinsensitivity, and lack of trust, which are the root cause of disparities in chronic disease as well as infectiousdisease, including COVID-19. The proposed project utilizes the ACN infrastructure to create a network of church-based testing sites in a segregated and underserved AA neighborhood in Chicago that will provide COVID-19testing and education as well as linkage to healthcare and social resources. Thirteen ACN pastors who servepredominantly AA congregations in the West Side of Chicago will form a coalition to promote community-wideCOVID-19 testing in local churches. Residents of all ages will receive COVID-19 education and free SARS-CoV-2 PCR testing with rapid turn-around of results from an on-site clinical team, as well as connection to localresources to address social needs, including food, housing, and medical care. Our specific aims are: (1) Conducta rapid needs assessment to identify barriers to and facilitators of COVID-19 testing to inform a tailored outreachand intervention strategy to increase COVID-19 testing among high-risk AAs; (2) (Primary Aim) Evaluate theimpact of the ACN COVID-19 testing intervention on uptake of testing among residents of target high poverty AAneighborhoods in Chicago; (3) Use the RE-AIM framework to assess the reach, adoption, implementation,maintenance and cost of the ACN COVID-19 testing intervention. Our primary analysis uses an interrupted timeseries framework, which is a quasi-experimental approach, to test whether the ACN testing intervention issuccessful at increasing uptake of testing by at least 20% among residents in the target neighborhoods.Completion of these aims will provide crucial evidence about the public health utility of this approach and informefforts to scale this intervention to increase testing uptake in other vulnerable urban areas in Chicago andnationally.",2020,2022,Rush University Medical Center,1616709,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09556,1R61HD105591-01,A data science approach to identify and manage Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection and Kawasaki disease in pediatric patients,"Summary - Since the SARS-CoV-2 pandemic began, the emergence of an associated novel multisysteminflammatory syndrome in children (MIS-C) has been reported. Interestingly, patients with MIS-C follow apresentation, management and clinical course that are somewhat similar to that of patients with Kawasakidisease (KD). Currently, the reason for such an overlap in clinical features and management is unclear andwhether this overlap is the result of a partially shared etiology or pathophysiology is the subject of fiercedebates. The degree of overlap implies that some of the clinical prediction tools that we have developed in thepast for KD could be repurposed to accelerate the development of clinical support decision tools for MIS-C. Inthis study, we will first (R61 component) systematically address the overlap between KD and MIS-C and createsalient machine-learning based prediction models for diagnosis/identification (Aim #1), management (Aim #2),and short- and long-term outcomes (Aim #3) of MIS-C based on our previously developed predictive models forKD in a process akin to transfer learning. Secondly (R33 component), we will validate and evaluate theperformance and clinical utility of these models in a predictive clinical decision support system for the diagnosisand management of pediatric patients presenting with features indicative of either MIS-C or KD. In this study wewill include 3 groups of patients: 1) patients with SARS-CoV-2 infection with MIS-C (CDC criteria) regardless ofwhether they have overlapping signs of KD, 2) patients with SARS-CoV-2 infection investigated for buteventually not diagnosed with MIS-C, and 3) patients with KD but without SARS-CoV-2 infection. Targeted datawill be collected from enrolled patients (900 for training and 450 for validation) for deep phenotyping andbiomarker measurements. Physician feedback on the predictions generated by the algorithm will be used toestablish clinical utility. Data required for model training will be accrued in the first two years of activity (R61period of the grant); the development of algorithms and their internal validation will occur concurrently. In thefollowing 2 years (R33 period of the grant), we will perform external validation, establish clinical utility, add real-time epidemiological surveillance data to the models and finally package, and certify the algorithms for futuredeployment and for the integration in electronic health records. This project will be a collaboration with theInternational Kawasaki Disease Registry (IKDR) Consortium. The IKDR Consortium has an active KD andpediatric COVID registry in 35 sites across the world and the number of sites is currently expanding to 60+ sites.More than 600 MIS-C patients have already been identified at IKDR centers, making this project clearly feasibleand perfectly positioning IKDR to perform this study. We strongly believe that the use of emerging data sciencemethods and of our previously developed algorithms in the context of KD, as opposed to focusing on MIS-Cpatients alone, will boost our understanding of the etiology and pathophysiology of both MIS-C and KD and willmore rapidly lead to the emergence of data-driven management protocols for patients with MIS-C.",2020,2022,Johns Hopkins University,917957,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C09557,3UH3CA233314-02S1,COVID-19 testing in Underserved and Vulnerable Populations Receiving Care in San Diego Community Health Centers,"PROJECT SUMMARY/ABSTRACTPronounced inequities and disparities in coronavirus disease (COVID-19)COVID-19 morbidity and mortalityhave been reported among Black and Latinx individuals, largely due to comorbid conditions and socialdeterminants of health. Approximately 95% of COVID-19 related deaths occur among individuals withunderlying medical conditions. Of all racial/ethnic groups, Latinx communities in San Diego County haveexperienced the greatest burden of COVID-19 disease and deaths. Furthermore, testing challenges to dateare evident, including long turnaround of test results and longer waiting times for Black and Latinxs comparedto whites. The goal of this community-engaged proposal is to develop, test, and evaluate a rapid, scalablecapacity building project to enhance COVID-19 testing in three regional community health centers (CHCs) inSan Diego County. In collaboration with our CHC partners, their consortium organization (Health QualityPartners), and community stakeholders, we propose the following Specific Aims: 1) Compare the effectivenessof automated and live prompts and reminders and their combination for uptake of COVID-19 testing amongasymptomatic adult patients with select medical conditions and those 65 years of age and older receiving careat participating CHCs. We also will invite all study participants to: a) receive a flu vaccination; and b) assessfeasibility and acceptability of study participants to refer adult household members who are essential workersfor COVID-19 testing; and 2) Gather patient, provider, CHC leadership, and community stakeholder insights toestablish best practices for future scale-up of COVID-19 testing sustainability and vaccination. Our goal is totest 9,000 patients (3,000 per arm). Our community-engaged project includes underserved (socioeconomicallydisadvantaged and large proportion of Hispanic/Latinos) and COVID-19 vulnerable individuals (patients withmedical conditions and those 65 years of age and older). Our approach considers regional COVID-19morbidity and mortality to address disproportionate infection and death rates among vulnerable andmarginalized populations who bear a disproportionate burden of the pandemic.",2020,2023,University Of California-San Diego,1207841,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C09558,3R01MD013852-02S3,Connecting our Neighborhoods Need for Enhanced and Coordinated Testing to Achieve Equity: CoNNECT to Achieve Equality,"ABSTRACTCOVID-19 infections, hospitalizations, and deaths are disparate across racial and ethnic groups in the UnitedStates (US), disproportionately impacting minority communities. Northwest Arkansas (Washington and BentonCounties) is a ""COVID-19 Hot Spot"" in the US, with the region reporting such stark racial/ethnic disparitiesrelated to COVID-19 that the Centers for Disease Control and Prevention (CDC) came to Northwest Arkansasto investigate in June and July 2020 and then the National Institutes of Health sent investigators in earlyAugust 2020. The CDC's July 2020 report documented that 45% of all adult cases in Northwest Arkansas wereamong Hispanic/Latinx patients and 19% were Native Hawaiian/Pacific Islander (NHPI) patients.Hispanic/Latinxs and NHPIs, only account for 17% and 2.4% of the two-county population, respectively.COVID-19 deaths in Northwest Arkansas were also disparate across race and ethnicity. NHPI deaths wereestimated to be more than 200 per 100K -much higher than the overall death ratio for the county of 5.10 per100K, as well as the death ratio for Whites of 4.03 per 100K. There is an urgent need to increase COVID-19testing and prepare for future vaccination trials, especially for the NHPI and Hispanic/Latinx communities ofNorthwest Arkansas. The uptake of current testing is low, less than 5%, and our needs assessment found thetop preferred locations identified were clinics with drive-through testing and drive-through testing in targetedhousing complex and neighborhood. We will use a community-based participatory research approach guidedby the Social Ecological Model (SEM) to target testing strategies that will have the greatest impact. Ourspecific aims are: Aim 1: leverage and fully engage our long-standing community-based partnerships toincrease COVID-19 testing and prepare for future vaccination trials; Aim 2: implement and evaluate accessand uptake strategies of two community-driven COVID-19 testing approaches to understand effectiveness andimpact for vulnerable populations; Aim 2a: evaluate which testing sites are most effective in reaching specificvulnerable populations based on age, race/ethnicity, and sex; Aim 2b: examine how social determinants ofhealth influence testing behaviors and preferred testing location; Aim 2c: conduct an implementation study todocument facilitators and barriers to implementation of community-based testing methods; and Aim 3: fullycollaborate with the RADx-UP Coordinating and Data Collection Center (CDCC) and other RADx-UP sites. Theproposed study aims are built directly on our collaborative needs assessment and recommendations from ourCommunity and Scientific Advisory Board (CSAB). Our current infrastructure and partnerships have beensustained for more than seven years and have been highly productive across multiple projects through local,institutional, and federal support. We are confident that we can leverage these partnerships to address COVID-19 mitigation efforts, including potential vaccine, and/or therapeutic implementation efforts.",2020,2022,University of Arkansas for Medical Sciences,715920,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2019 +C09559,3P51OD011107-59S8,California National Primate Research Center,"PROJECT ABSTRACTThis application from the California National Primate Research Center (CNPRC) located on the University of California(UC) Davis campus, seeks to obtain federal funding in the amount of $3,100,000 through the AdministrativeSupplements for Alteration and Renovation (A&R) and expansion of breeding to provide rhesus macaques for COVID-19 research. The Alteration and Renovation funds will be used to renovate a shade structure for a single ½ acre outdoorcorral, perform repairs to the interior corral structure, and renovate and provide heating to five outdoor pens. Thebreeding colony expansion for the CNPRC breeding colony will begin in Year 1 and continue in Year 2. Two previouslyrenovated outdoor breeding corrals will be populated with approximately seventy rhesus macaques in each corral inYear 1. The five outdoor pens that are renovated and have heating installed will be used for animal production in Year2. These outdoor pens are smaller and house approximately 10-15 animals. The CNPRC will acquire forty young rhesusmacaques from the Caribbean Primate Research Center (CPRC) in Year 1. These animals will complete the CNPRC90 day quarantine and will then be housed in the smaller outdoor pens for repeated testing to confirm their viral statusbefore combining them with juvenile rhesus from the CNPRC colony. We will also use ten indoor gang cages for housingof young rhesus, formation of stable social groups, repeat viral screening, and eventual transfer to breeding corrals inthe future. The corral that is renovated in Year 1 will then be used to house an additional 70 animals to form the thirdbreeding corral for colony expansion. The forty young rhesus acquired from the CPRC will be integrated into the thirdbreeding corral along with smaller breeding groups in the outdoor pens. Funds are requested in Year 2 to pay the perdiem for the expanded breeding group as well as hire additional staff to provide for the animal care, colony management,and veterinary care needs. This funding for additional staff is needed because by Year 2 we will designate approximately350 animals including the forty animals from the CPRC for breeding and overall colony expansion. Their primaryassignment will be to the expanded breeding colony. When the 200 females begin breeding, the estimated production(77% live birth rate/female) will produce an additional 154 rhesus on an annual basis for COVID and pandemic focusedresearch.The specific aims of the proposed project are to: • Renovate one ½ acre corral and five outdoor pens to be used for expansion of the CNPRC breeding colony • Establish three additional breeding corrals, five outdoor pens, and ten indoor gang cages for expanded breeding for COVID-19 and future pandemic research • Expand CNPRC animal care, colony management, behavior and veterinary staff to provide care for the expanded colony • Commit 350 adult rhesus to an expanded breeding colony with the goal of increasing current CNPRC production by 154 infants/year",2021,2023,University Of California-Davis,40119,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,,,2021 +C09560,3U54AG063546-02S5,NIA AD/ADRD Health Care Systems Research Collaboratory,"PROJECT SUMMARYThe SARS-CoV-2 pandemic has had a devastating impact on the nursing home and residential care populationin the US and beyond. Between 40% and 80% of all COVID-19 deaths have been among residents of nursinghomes or assisted living facilities. Despite a declining mortality rate among those who have confirmedinfection, the virus' impact on nursing home residents' functioning and quality of life remains significant due toboth COVID-19's medical sequelae and the social isolation arising from visitor restrictions, social interactionsand group activity restrictions. As of September 2020, there are 4 vaccines in Phase 3 trials in the US. Thesetrials aim to recruit over 30,000 thousand subjects each, but few will be frail, aged, or with multiple morbidities.However, frail older persons living in congregate settings are in the top priority group for distribution of the virusonce approved. However, since there is considerable evidence that the immune system of frail older people isnot as responsive as that of the younger population on which these vaccines are being tested, carefulmonitoring of their response to the vaccine will be required. Presently, the Centers for Disease Control (CDC)has limited ability to monitor for adverse events (AEs) of a SARS-COV-2 vaccine in the nursing homepopulation. Since April, 2020, Brown University's Center for Gerontology & Healthcare Research has beenworking the Genesis HealthCare, the largest provider of institutional long-term care in the country with some400 facilities in 25 states. Genesis hosts its own electronic medical record (EMR) system and, working withBrown IT staff, has been transferring most of the data in its EMR to Brown nightly. We propose to use thisextensive, detailed and timely data infrastructure to build a nursing home based AE monitoring system tomonitor the incidence of a variety of different types of adverse effects experienced by nursing home residents.We propose to: 1. Design and build an updated system for identifying, flagging and highlighting within residentchanges in clinical status; 2. convene a team of experts in clinical geriatrics and immunology to propose amultiplicity of diagnoses, functional, symptom or vital sign changes indicative of an adverse reaction to theadministration of a vaccine; 3. develop such indicators specifically focused on the population of residents withdementia and/or significant cognitive impairment; and, 4. design and test a twice-weekly reporting scheme thatcould be put into practice as soon as Genesis facilities begin to receive the different types of vaccine.",2020,2024,Brown University,273187,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase IV",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Adverse events associated with immunization,2019 +C09561,1U01DC019573-01,Rapid olfactory tools for telemedicine-friendly COVID-19 screening and surveillance,"The COVID-19 pandemic is the most devastating infectious disease outbreak in a century, particularly inunderserved and minoritized communities. In 2020 alone, it will cost a million lives. It continues to wreakeconomic havoc worldwide. Therefore, it is critical to develop new tools that can mitigate the spread of SARS-CoV-2, the virus that causes COVID-19. Rapid screening tools can identify potentially infected individuals whocan then be isolated/quarantined from the uninfected and directed towards further testing and treatment.Unfortunately, definitive viral testing for SARS-CoV-2 has proven difficult to implement in many countries,including the US, due to technical, financial and governmental hurdles to universal access and timelyprocessing. Symptom-based screening offers a valuable, albeit imperfect, complement to viral testing that canhelp identify many individuals with the disease for isolation as well as treatment. A major challenge withsymptomatic testing is that COVID-19 is highly protean: the heterogeneity of symptoms means no singlesymptom or constellation of symptoms is definitive diagnostically. Still, there is growing evidence that suddenpartial or complete olfactory loss - even more than other symptoms such as fever or dry cough - is the singlebest predictor of COVID-19. In this proposal, we will develop and implement objective, self-administered smelltests for the purpose of identifying individuals with COVID-19 prior to, or in the absence of, viral testing, as wellas for use in population-level surveillance of COVID-19 spread. Several kinds of objective tests have beenused in clinical or laboratory settings to assess an individual's olfactory ability, including those that test theability to identify or discriminate odors as well as procedures to determine the lowest concentration anindividual can reliably perceive (i.e., odor detection threshold). Each approach has technical and logisticaladvantages and disadvantages, and each captures different aspects of olfactory dysfunction. RegardingCOVID-19, it is unknown what type of measure has the highest specificity or sensitivity. In Aim 1, we will use self-administered objective testing of odor identification and odor detection threshold in SARS-CoV-2-tested individuals to determine which olfactory measure is the best predictor of COVID-19. In Aim 2, we will use objective smell testing to assess whether population monitoring of olfactory loss in university, municipal orother community settings can serve as a sentinel of COVID-19 community spread. Together, our studies willprovide a rapid, remote-friendly, cost-effective, scalable, non-intrusive method to screen for COVID-19 at theindividual level and to assess prevalence in communities, especially those that have been traditionallyunderserved by the health care system and public health infrastructure.",2020,2022,University Of Florida,485408,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2020 +C09562,3R01HD091218-04S1,"Safety, Testing/Transmission, and Outcomes in Pregnancy with COVID-19 (STOP-COVID-19 study)","ABSTRACTIn response to NOT-OD-20-120, we submit this competitive revision of grant # R01 HD091218 04(Mechanisms of Zika Virus Maternal-Fetal Transmission) to investigate the impact of COVID-19 and testing forthe causative virus, SARS-CoV-2, among pregnant women and their infants. Pregnant women are a vulnerableand high-risk population, as COVID-19 is associated with an increased risk of preterm birth, cesarean section,and maternal intensive care. The objectives of this study are to: (a) evaluate the full impact of SARS-CoV-2 inpregnancy to inform testing strategies, (b) examine the factors that impede testing during pregnancy, and (c)use study data to devise implementation strategies that improve SARS-CoV-2 testing in pregnancy andprenatal care during the pandemic. To do so, we propose to prospectively enroll two cohorts of pregnantwomen: 1) exposed (SARS-CoV-2 positive), and 2) unexposed (SARS-CoV-2 negative as defined by antibodytesting at the beginning of pregnancy, every trimester, and at delivery). Women who initially enroll asunexposed but later test positive for SARS-CoV-2 antibodies will cross over to the exposed cohort. In total, anestimated 179 pregnant women will be followed per cohort. In Aim 1, we will evaluate patients' and providers'perceptions of SARS-CoV-2 testing during pregnancy and the influence of COVID-19 on maternal care-seeking behavior and anxiety via surveys and semi-structured interviews. We hypothesize suboptimal uptakeof testing among pregnant women due to the fear of repercussions from a positive test. In Aim 2, we willdetermine the effect of SARS-CoV-2 infection during pregnancy on the risk of preterm birth and other adversepregnancy outcomes in symptomatic and asymptomatic disease. We hypothesize that SARS-CoV-2 infectionwill increase the risk of preterm birth by 12%, regardless of disease severity. In Aim 3, we will estimate the risk of mother-to-fetus SARS-CoV-2 transmission and viral presence in umbilical cord blood, placenta, and amniotic fluid by assaying for viral RNA in the neonate, cord blood, and placenta. We hypothesize that SARS-CoV-2 can be transmitted from mother to fetus. Collectively, Aims 1-3 will be interpreted by investigators, ourScientific Advisory Board (experts in obstetrics, infectious disease, implementation science, disparities) andour Community Advisory Board (an obstetric social worker, pregnant women, and a director of a communityobstetrics clinic) who will apply data to devising targeted implementation strategies designed for rapidcommunity dissemination to improve testing and prenatal care. In sum, this study will fill knowledge gaps onthe impact of SARS-CoV-2 infection and current utilization of diagnostic testing in pregnancy. Further, it willcreate implementation strategies to overcome barriers to testing, increase uptake, and promote acceptanceand sustainability of testing. Lastly, this study will help determine optimal testing strategies by examining thenecessity of testing for asymptomatic disease, inform prenatal care plans by assessing the full impact ofinfection, and contribute to our ability to counsel women and create prenatal care plans if they are pregnant orconsidering pregnancy.",2020,2022,Washington University,791317,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Approaches to public health interventions | Community engagement | Communication",2020 +C09563,1R61HD105594-01,Diagnosis of MIS-C in febrile children,"PROJECT SUMMARYThe recent emergence of SARS-CoV-2 and resultant pandemic of COVID-19 disease has overwhelmed globalhealth systems and led to over 200,000 American deaths to date. While initial reports suggested that SARS-CoV-2 infection in children was generally benign, a novel post-inflammatory syndrome known as multisysteminflammatory syndrome in children (MIS-C) has now been described. MIS-C in children is characterized by fever,systemic inflammation, and end-organ involvement, and the majority of patients are IgG seropositive for SARS-CoV-2. Because the clinical features of MIS-C overlap with other infections and inflammatory disorders, newstrategies for diagnosis of MIS-C in febrile children are urgently needed. Our immediate objective (during theR61 phase) is to determine the reproducible changes in breath, urine, and salivary volatile composition in chil-dren diagnosed with MIS-C. We will integrate these discovery studies with clinical and immunological profiling todevelop (during R61 phase) and validate (during R33 phase) a novel and much-needed MIS-C diagnostic, whichis expected to have a major impact on care of febrile children. Our long-term goal to develop a diagnostic strategyto distinguish children with MIS-C from children with other causes of fever. Supported by our strong preliminarydata that indicate our expertise and feasibility of this strategy, our objectives will be met through three specificaims: 1) Characterize breath biomarkers in children with MIS-C (R61); 2) Relate breath VOC changes to virolog-ical, disease severity, and immunological features of MIS-C (R61); and 3) Validate our novel MIS-C diagnosticfor clinical use (R33). The proposed research is significant, because we will progress in development of new,much-needed MIS-C rapid diagnostic tool.",2020,2022,Children'S Hosp Of Philadelphia,879259,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C09564,3R01LM012309-04S1,Predicting Diabetic Retinopathy from Risk Factor Data and Digital Retinal Images,"African American and Latinx communities nationally and in California not only bear a disproportionate burdenof COVID-19 positive cases and deaths but are also not taking part in COVID-19 testing for a wide range ofunderstudied reasons. This can have profound implications in safety net health care settings where vulnerablepatients, who are in need of clinical procedures to prevent significant morbidity, are refusing such potentiallylifesaving procedures because of fear of COVID-19 testing and/or contracting COVID-19. The Los AngelesCounty Department of Health Services (LACDHS) is the second largest publicly operated county safety nethealth care system in the United States, serving more than 750,000 patients annually. Timely access to healthcare in this under-resourced, high-need setting has been an ongoing challenge for its majority Latinx andAfrican American patients. With the current pandemic, COVID-19 testing for patients has become an essentialfirst step in the provision of critical procedural care. However, the range of reasons why patients refuseCOVID-19 testing is little understood. To this end, we propose to explore the obstacles to COVID-19 pre-procedural testing and provide COVID-19 specific training to LACDHS Community Health Workers (CHWs)from these same communities to effectively address: a) the primary goal of increasing COVID-19 testing forindividual patients, and the secondary goals of b) facilitating needed procedural care in a timely manner for thesafety net health system, and c) developing a sustained public health presence in these communities to buildtrust and preparedness for critical COVID-19 related future needs. Trained CHWs can help to more effectivelyovercome obstacles to COVID-19 testing, including historical barriers of mistrust, provide COVID-19 healtheducation, help address social determinants of health and help facilitate technological literacy to improvepatient access to testing and care in a telehealth environment. The proposal uses a multidisciplinary, mixed-methods approach including unsupervised machine learning and qualitative interviews to systematicallyexplore barriers and facilitators to COVID-19 testing among vulnerable safety net patients. We will then trainclinically based, ethnically/linguistically matched CHWs to implement a hypothesis-driven interventionconsisting of six group classes and six personalized patient encounters with African American and Latinxsafety net patients. This study has the following specific aims: Aim 1- Utilize machine learning methods toassess whether there are characteristics that define African American and Latinx safety-net patients whoengage in or refuse COVID-19 testing; Aim 2 - Conduct in-depth interviews with African American and Latinxpatients who either declined or accepted COVID testing to explore contextual, behavioral, and attitudinalfactors shaping patient circumstances and concerns; Aim 3 - Develop, implement, and pre-test a CHWintervention with the information from Aims 1 and 2, utilizing a randomized control design among AfricanAmerican and Latinx safety net patients to assess the effect of the CHW hypothesis-driven intervention ontrust, self-efficacy, and intent to participate in COVID-19 testing.",2020,2021,Charles R. Drew University of Medicine and Science,399963,Human Populations,Black | Other,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09565,1U24LM013755-01,RADx-Rad Discoveries & Data: Consortium Coordination Center Program Organization,"ABSTRACT   Preparing SARS-­CoV-­2 testing data for reuse requires making the data syntactically and semantically equivalent. Standardization  of  terminologies  and  a  common  data  model  accomplish  the  former,  while  the  latter  is accomplished  through  understanding  the  data  and  making  it  comparable  across  RADx-­rad  awardees  by benchmarking against known gold standards. The standardization of samples is as important as standardizing the data, particularly in the highly innovative RADx-­rad program, where new technologies will be developed or optimized for deployment in various settings. Highly motivated RADx-­rad awardees will receive advice on how their diagnostics compare to FDA-­approved ones, with each other, how their diagnostic performs in independent testing,  as  well as how  to ensure  the  tests  are usable  in  real  world  settings.  In  collaboration  with  University  of Texas  Health  Science  Center  at  Houston,  University  of  California San  Diego  researchers  in  informatics/data science and infectious diseases with ample experience in leading large consortia have designed a unique RADx-­rad  Consortium  Data  and  Coordination  Center  (radCDCC).  This  center  is  based  on  three  pillars:  (1)  effective administration and coordination among awardees, NIH, and other programs;; (2) innovative approaches and tools to  collect  and  standardize  data  and  metadata  to  promote  findability,  accessibility,  interoperability  and  reuse (FAIR)  for  data  sharing;;  and  (3)  principled  preparation  of  standardized  samples  with  known  quantities  of  viral loads, and standardized procedures for testing new diagnostics to allow comparison across tests and calibration of  new  technologies.  Backed  by  sophisticated  HIPAA-­compliant  cloud  services,  user  friendly  web-­tools,  and extensive  support  from  UCSD's  facilities  for  computation and  for  clinical  research,  the  radCDCC will  interface with other RADx programs and other COVID-­19 focused programs at NIH to ensure alignment of awardees, NIH and the public in the pursuit of effective, affordable, and deployable new technologies for testing.  ",2020,2024,University Of California-San Diego,5954423,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,,,2020 +C09566,1U01AA029348-01,Detection and Automatic Privacy-Protected Contact Tracing System Designed for COVID-19,"Project Summary/Abstract The COVID-19 pandemic has rapidly spread across the world, bringing death, illness, disruption to dailylife, and economic crisis to businesses and individuals. The situation has been exacerbated after the schoolsand companies reopened due to economic pressure. One of the key failures in COVID-19 containment isunderlined by the inability of our healthcare system in real-time detection in point-of-care (POC) and end-usersettings and precise tracing with privacy protection of active infections. The fundamental limitations of currentgene-based assays stem from their reliance upon amplification and detection of the viral genetic materialseven if there were no intact/infectious viruses. These tests require labor-intensive, laboratory-based samplepreparation protocols for virus lysis, extraction of genetic materials, purification of the isolated materials,thermal cycling for enzymatic amplification of viral nucleic acid sequences, and interpretation of complexresults by professionals. To accurately determine the infectivity of the infected individuals, contaminatedobjects and environments, and provide guidance for patients, public and authorities to better manage treatmentand containment, we seek a new paradigm for rapid and direct pathogen detection and identification in whichthe intact virions are directly recognized through their distinct surface epitope features, and the resultantfluorescent signal is immediately captured by an end-user smartphone, followed by automatic data transitionand event tracing in a blockchain-encrypted manner. To achieve specific recognition of SARS-CoV-2 virions,we customized a designer DNA nanostructure (DDN)-based capture probe that harbors a macromolecular""net"" whose vertices precisely match the intra- and inter-spatial pattern of SARS-CoV-2 trimeric spikeglycoprotein clusters, and integrates a net-shaped array of SARS-CoV-2 spike specific-targeting aptamers.This aptamer-DDN is designed for maximum affinity and specificity binding with spikes on intact virions in apolyvalent and pattern-matching fashion. Once bound to intact virions, the DNA ""nets"" trigger the release offluorescence. This fluorescent signal can be readily and automatically detected by a membrane-shaped andsmartphone-based fluorimeter attached to the end-users' phone cameras. The acquired results will beassociated with user device IDs that are cyber-protected before tracing. We propose to combine DDN captureprobes and a smartphone device to develop and demonstrate a rapid, room temperature, single-step, virus-specific, and ultrasensitive detection of SARS-CoV-2 virus, in which the detection results can be acquiredwithin 5 minutes upon exposure, at the user end, allowing tracing the presence of viruses without affecting userprivacy. The signal to result transition, result to ID association, individual track and interacting network tracingwill be blockchain-encrypted to ensure information security for individual privacy, while tracing informationwould be available to health authority for public health benefits.",2020,2022,Louisiana State University,450305,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09567,1U01AA029324-01,Minimal False-alarm Touch-based Detection of SARS-Cov-2 Virus Particles using Poly-aptamers,"PROJECT SUMMARY/ABSTRACTAvailable tools for detection of SARS-CoV-2 virus require extensive sample preparation and/or expensive lab-based equipment to obtain accurate results. The objective in this proposal is to build a touch-screen sensor arrayto directly capture, detect, and identify model SARS-CoV-2 virus particles with minimal false alarms. This ambi-tious goal will be achieved by the interdisciplinary team of GE Research scientists and engineers and will be asynergistic combination of the proposed innovations and the prior scientific and engineering accomplishmentsof the team. Our proposed solution is based on several innovations driven by eliminating a need for a dedicated sam-pling step and solving the problems of detection and reliable selective recognition of virus particles, performingdetection/recognition operation in a two-dimensional (2D) format of biosensors, e.g., as a touch-screen surface,and having this technical solution as a low-profile, low power, unobtrusive device that can be adapted to diverseapplication scenarios. Innovations of the proposed proof-of-principle touch-screen detector are in three main areas. For virusrecognition, we will create new multifunctional bioreceptors. Our transduction principle will be based on ourearlier reported transduction with the significantly enhanced performance. Our touch surface design will have a2D array of biosensors. The proposed proof-of-principle sensor will be developed in five aims. Aim 1 will focus on demonstration of new multifunctional bioreceptors. Aim 2 will focus on validation of the functionality of these multifunctionalbioreceptors upon their immobilization on sensor surface. Aim 3 will focus on demonstration of sensing of mod-el virus particles in a layout of 2D array of biosensors. Aim 4 will focus on demonstration of virus recognitionwith immobilized multifunctional bioreceptors in variable ambient conditions. Aim 5 will focus on demonstra-tion of enhanced detection and recognition of model virus particles in the same layout of 2D array of biosensorsas in Aim 3, but under variable ambient conditions. The findings in this proposed work will change the state-of-the-art biosensing paradigm and will improve the scientific knowledge, technologies, and workflow practice forvirus detection.",2020,2022,General Electric Global Research Ctr,581785,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +C09568,1U01AA029316-01,"Touchscreen-compatible, real-time electrochemical sensing of SARS-CoV-2","PROJECT SUMMARYThe SARS-CoV-2 coronavirus, the cause of the COVID-19 global pandemic, is efficiently spreadand has reached over 27 million confirmed cases as of September 8, 2020. There is therefore anurgent need for new technologies that can provide early detection of virus, reducing thetransmission and infection rate. The goal of this proposal is to develop an integrated biosensor-touchscreen that sensitivity reports surface contact with SARS-CoV-2. In our preliminary work,we have identified several aptamers that bind specifically to the envelope-anchored trimeric spike(S) protein of SARS-CoV-2, but not of SARS-CoV or MERS. In comparison to antibodies,aptamers are synthetic molecules that more thermally stable and lower cost while providingsimilar specificity and affinity of target binding. In this application, we propose to integrateaptamer-based biosensing of SARS-CoV-2 into a touchscreen device. Our main objectives are to1) engineer conformation switching aptamers for electrochemical sensing of SARS-CoV-2binding, 2) develop nanogap capacitive sensors as a uniquely complementary approach tocapacitive touchscreen technology and 3) build and test an integrated biosensor and touchscreenarray that can detect SARS-CoV-2 from patient samples. Successful completion of these aimswill result in a novel automatic sensing platform for SARS-CoV-2. This technology could transformpersonal device touchscreens as well as to multi-user touchscreen devices in hospitals, airports,libraries, restaurants, for early detection, curbing transmission rates from secondary exposure.Importantly, the developed technology could be adapted for other electronic sensing platforms,and easily applied for future pathogen detection.",2020,2022,University Of Washington,466500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Diagnostics | Medicines, vaccines & other technologies",2020 +C09569,3R21MH122010-01S1,"Understanding the COVID-19, Racism, and Violence Syndemic and its Effects on COVID-19 Testing Disparities","Project SummaryBlack communities in the US are experiencing three converging public health crises: COVID-19, systemicracism, and community and police violence. Black Americans are significantly less likely to receive a neededCOVID-19 test and have higher rates of COVID-19 infection and death than white Americans. Additionally,Black communities have experienced a surge in gun violence in 2020 and continue to be victims of policeharassment and violence, resulting in large-scale social justice demonstrations. The convergence of theseepidemics has created a syndemic, wherein racism, violence, and COVID-19 cluster in predominantly Blackand low-income communities. The proposed study aims to characterize this syndemic to understand howpersonal and systemic racism and violence in Black communities may influence COVID-19 testing decisions.This mixed-method study with Black residents of Chicago, IL will result in community-driven recommendationsto enhance COVID-19 testing and prevention strategies and address this emerging syndemic. We will examinethe potential mediating pathways of medical mistrust, psychological trauma and stress, and economic injustice.Additionally, we will take a strengths-based approach to understand potential protective factors includingneighborhood cohesion, social support, and access to health care. The specific aims of the study are to: 1)Qualitatively examine how experiences of racial discrimination, community violence, and police violenceinfluence trust in and engagement with healthcare systems and contribute to decisions around COVID-19testing and mitigation strategies (e.g. social distancing) among Black individuals in Chicago (N=50); 2)Quantitatively assess the prevalence and correlates of COVID-19 testing among Black residents in Chicago (N= 500) and characterize the COVID-19, racism, and violence syndemic; and 3) In partnership with aCommunity Advisory Council, use an integrative translational workshop approach and intervention mappingtechniques to develop community and data-driven recommendations and an intervention blueprint for localhealth departments, researchers, and public health organizations to improve COVID-19 testing among BlackAmericans. This study will result in policy and research recommendations, community resources, and a'shovel-ready' intervention blueprint to enhance COVID-19 testing and address this emerging syndemic.",2020,2022,Medical College Of Wisconsin,470715,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09570,1U01DA053899-01,"Improved scalability, sensitivity, and interpretability of pathogen detection, including SARS-CoV-2, in wastewater using high-throughput, highly multiplexed digital array PCR technology","PROJECT ABSTRACTPresently, the application of molecular technology such as RT-qPCR and digital PCR (dPCR) to quantifySARS-CoV-2 and related targets in wastewater is cumbersome, time consuming, and costly. Whileprogress has been made on the development of methods and the interpretation of data, much remains tobe improved for the technology to be used as a public health management tool. A major drawback in thecurrent approaches are 1) the lack of streamlined and consistent pre-analytical processing steps, 2)coverage across the relevant targets requires a high number of reactions (>20) from any single sample toprovide quantitative information, and 3) a lack of vision on the development of a pathogen/marker panel,much like those used in clinical arenas, for interpretation of the data across different states, regions andnations. The goal of this project will be to successfully navigate these three limitations towarddevelopment of a public health warning system that is not dependent on clinical testing and has the abilityto rapidly address novel pathogen threats in the future.",2020,2022,University of North Carolina at Chapel Hill,997507,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2021 +C09571,1U18TR003807-01,Multi-parametric Integrated Molecular Detection of SARS-CoV-2 from Biofluids by Adapting Single Extracellular Vesicle Characterization Technologies,"AbstractThe World Health Organization has recognized a global pandemic of novel coronavirus pneumonia (COVID-19)from exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses (CoVs)are membrane-enveloped positive-sense, single-stranded RNA viruses decorated with membrane proteins. Thespike (S) glycoprotein is implicated in the viral attachment and fusion to host cells via the human angiotensin-converting enzyme 2 (hACE2). There are different assays to test for COVID-19, including nucleic acid, antigen,and serological tests that can be used in hospitals, point-of-care, and large-scale population testing. Nucleic acidtesting is the standard method for the detection of SARS-CoV-2, which consists of the amplification of viral RNAfrom nasopharyngeal swabs (NPS) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).Furthermore, given the invasive nature of NPS, saliva is being considered an alternative for detection. Methodsthat bypass RNA extraction, as well as isothermal amplification such as loop-mediated isothermal amplification(LAMP), have been developed to improve the speed of viral RNA detection. However, viral protein expressioncannot be detected by qRT-PCR. Serological tests, on the other hand, are based on host antibodies against thevirus (IgG/IgM). Although fast, these tests suffer from significant false negative/positive. Besides, they do notdetect a current infection. Therefore, to relieve the current healthcare crisis, new technologies capable ofsimultaneous viral RNA/protein detection at the single virus level and host antibody response detection from abody fluid in an integrated device would be highly valuable for enhanced COVID-19 diagnosis.Recently, our group, as part of Phase 2 of the Extracellular RNA Communication Consortium (ERCC2), hassuccessfully developed a microfluidics technology capable of capturing individual exosomes from biofluids andthen simultaneously quantify both exosomal surface proteins and RNA cargo. Given the resemblance in sizeand other characteristics between exosomes and coronaviruses, our technology can be adapted for COVID-19diagnosis. Therefore, we propose to develop and validate a safe-to-use version of our microfluidics system fordirect detection of SARS-CoV-2. The integrated system is capable of multi-parametric detection for enhancedCOVID-19 diagnosis. The platform will be engineered to simultaneously quantify both viral protein, viral RNA,and host antibodies (IgG/IgM) in the same sample, enabling diagnosis, disease status, and prognostic assessment. Model systems, including host IgG/IgM from patient serum, standard synthetic vesicles (SVs), andheat-inactivated SARS-CoV-2 viral particles (SVVs), will be designed and spiked in biofluids to validate andcalibrate the system. To demonstrate the clinical utility, our biochip technology will be deployed and tested usingdifferent biofluids from COVID-19 patients at two independent laboratories (Institute of Systems Biology inSeattle and The Ohio State University (OSU) Wexner Medical Center in Columbus). Measurements obtainedfrom the biochips will be compared to standard qRT-PCR and ELISA methods. A transition plan will be preparedfor FDA Emergency Use Authorization (EUA) application of the biochip technology through a COVID-19 clinicaltesting laboratory at OSU Wexner Medical Center. A commercialization plan will also be developed via licensingto a biotech company.We have assembled a multi-disciplinary team with extensive knowledge and experience in nanobiotechnology,microfluidics, micro/nano-fabrication, infectious diseases, and clinical COVID-19 patient sample collection andtesting. The proposed aims and milestones are given as follows:Specific Aim 1: Development of an integrated biochip to simultaneously capture, fix, and characterizesingle SARS-CoV-2 and IgG/IgM proteins. Milestones. (i) Sorting, capture, and quantitative analysis ofselected proteins and viral RNA in single virus in spike experiments with >95% repeatability; (ii) A sensitivity ofsingle virus detection with >90% repeatability and 5-fold better sensitivity than the current qRT-PCR and ELISAmethods. Specific Aim 2: Testing of single SARS-CoV-2 virus and associated IgG/IgM in biofluids fromCOVID-19 patients. Milestones. (i) Quantitative analysis of clinical samples with >95% repeatability; (ii) 95%of concordance for the detection of SARS-CoV-2 between the biochip technology and the lab-based qRT-PCRand ELISA. Specific Aim 3: Biochip technology transition plan. Milestones. (i) Submission of documentationto the FDA Center for Devices and Radiological Health (CDRH) for EUA; (ii) Scale-up commercialization plan forGMP chip production.",2020,2022,Ohio State University,900019,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2020 +C09572,3R34AT010661-02S1,"Social, Ethical, and Behavioral Implications (SEBI) Research on COVID-19 Testing and Vaccine Uptake among Rural Latino Migrants in Southwest Florida","Project Summary Latino youth have the highest prevalence of obesity as compared to Black or White youth, and are at high-risk for adult obesity-related complications including cardiovascular disease. Moreover, Latino youth living inrural communities have an increased risk of adult obesity and mortality due to obesity-related chronic diseasethan Latinos living elsewhere. We synthesized our prior childhood obesity intervention and tailored ourevidence-informed, theory-based, multi-family behavioral intervention, Adaptando Dieta y Acción Para Todos(ADAPT), to the acculturation status, language, and national origin or our target population - obese, schoolaged (8-12 years old) Latino youth and their parents living in rural areas. However, because the role of parentstress on obesity has not been adequately addressed in interventions aimed at reducing obesity in Latinoyouth, we argue that mindfulness parent stress reduction strategies may be a key component to improvingeating and physical activity (PA) behaviors in both children and their parents. This NIH Stage I R34 proposes arefinement and optimization of the original ADAPT obesity intervention protocol to include mindfulness parentstress reduction strategies (now ADAPT+) (Stage IA) and feasibility assessment of ADAPT+ implementation(Stage IB). This mixed methods R34 sets the basis for a Stage 2 larger R01 trial to determine ADAPT+'sefficacy in improving Latino families' eating and PA behaviors. Two main aims guide our application.Aim 1: Refinement of ADAPT+ (ADAPT + mindfulness parent stress reduction) intervention.• We assess acceptability of the integration of mindfulness parenting stress reduction into ADAPT to increase healthy lifestyle behaviors by: conducting a series of focus groups with our community health facilitators/ promotoras and parents of children (8-12 years old) with obesity to obtain feedback about and refine each of our 8 integrated sessions and evaluate optimization of ADAPT+ sessions.Aim 2: Feasibility and Acceptability trial. A randomized trial testing feasibility of ADAPT+ vs. EnhancedUsual Care/EUC conducted in two rural communities evaluates:• study sample selection and recruitment, willingness to be randomized and retention.• fidelity of intervention administration, intervention adherence, and further refinement of manuals.• feasibility of data collection procedures, including collecting a battery of measures from parents and children, data quality and sensitivity of our measures to our intervention effects over time - (pre- post- 3 mos post).• We anticipate that compared to EUC, ADAPT+ dyads will have a lower attrition rate and will report greater satisfaction. We also explore whether our eating, PA and stress indices are sensitive to the intervention.This application is significant, as it addresses an urgent public health epidemic among a specific at-risk,ethnic and geographical minority group; innovative, as it implements a unique intervention that addressesmany limitations in the current state of obesity prevention and employs a rigorous scientific approach.",2020,2022,University Of South Florida,502908,Human Populations,Other,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Rural Population/Setting,Internally Displaced and Migrants,Unspecified,Clinical | Non-Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2019 +C09573,3U01EB025136-03S1,Implantable Bio-Artificial Pancreas (iBAP),"PROJECT SUMMARY/ABSTRACTAs of May 25th, 2020, there were over 5.5 million confirmed cases of COVID-19 worldwide and around 1.7million in the US, where almost 100,000 deaths have occurred. Acute Respiratory Distress Syndrome (ARDS)presents secondary to COVID-19 and is primarily treated by mechanical ventilation. Of all hospitalized COVID-19 patients, around 20% will be intubated and mechanically ventilated. Unfortunately, ARDS patients areespecially susceptible to ventilator induced lung injury (VILI) and as many as 80% of intubated COVID-19patients have died. In contrast, ECMO bypasses the lungs, thereby avoiding VILI, and the patient's blood isdirectly oxygenated using an extracorporeal circuit containing a gas-permeable membrane. While ECMO hasshown increased survival relative to mechanical ventilation, the complexity of the ECMO procedure, associatedbleeding and clotting risks, and labor intensiveness has restricted its use. We propose to develop a newoxygenator membrane constructed from silicon nanopore membranes (SNM). The enhanced biocompatibilityand increased gas flux of the SNM will enable the Silicon Membrane Oxygenator (SiMOx) - a compact andpotentially anticoagulation-free ECMO system. The SiMOx will establish a new paradigm of ""set it and forget it""blood oxygenation that is characterized by decreased operational complexity, diminished bleeding/clottingrisks, and reduced personnel needs.",2020,2021,University Of California-San Francisco,806915,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2017 +C09574,3R44ES028145-03S1,Phase II - HazPrep Worker Training - Community Risk Profile - COVID-19 Rapid Response,"PROJECT SUMMARY/ABSTRACTCOVID-19 Supplement to HazPrep Phase II. Original Summary: A worker's personal hazard profile (PHP) is afunction of hazards present and his/her exposure level to those hazards. Workers with an elevated level of riskare those who can be engaged in activities related to - or working around - hazardous materials, wastegeneration, removal, containment, transportation, and emergency response. inXsol's Phase I feasibility studyverified the appeal and effectiveness of a new form of crowdsourced social learning platform. Our approachusing cloud technology creates a dynamically growing library of incidents/scenarios, highly personalized(occupation/task/geo) risk profile and generates learning activities to train on risk awareness and mitigationtechniques. The Phase II proposal includes implementation of an innovative use of big data algorithms forcommunity profiles and fusion with PHP allowing for targeted and personalized training completing the HazPrepprototype developed and exercised by our beta test team in Phase I.",2020,2021,"Inxsol, Llc",86019,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2017 +C09575,1U01AA029345-01,Rolosense: An innovative platform for automatic mobile phone readout of active SARS-CoV-2 particles,"Project AbstractThe ultimate goal of this proposal is to develop a novel platform technology for automatic surveillanceand tracing of airborne SARS-CoV-2 virus particles in real time. The centerpiece of this proposal is the""Rolosense"" technology which leverages a DNA micromotor as the virus sensing and transductionmaterial (VSTM) that can be detected by a conventional smart phone camera. This provides bothgeographical tracing and surveillance. Rolosense motor are comprised a DNA-coated spherical particle(5 micrometer diameter) that hybridizes to a surface modified with complementary RNA. The particlemoves at speeds of over 1 micron/minute upon the addition of RNase H, which selectively hydrolyseshybridized RNA but not single-stranded RNA. DNA motors coated with virus binding ligand (VBL) stallin presence of SARS-CoV-2 virus particles. Because motors move autonomously for distances up tomillimeters without intervention, the assay is fully automated, and conventional steps such as viralinactivation, RNA isolation and amplification are not required. The readout is performed using anautomated smart phone app for particle tracking without the need for a spectrophotometer orfluorometer. Preliminary data shows realtime SARS-CoV-2 pseudovirus particle sensing. Milestonesinclude the screening and identification of high affinity and high specificity VBLs. Both aptamers andantibody VBLs will be screening and validated. Simulations and experiments will be used to understandthe role of temperature and environmental conditions in modulating Rolosense performance.Multivalent display of VBLs with DNA origami will enhance avidity. Finally, microfluidic chips withairborne droplet capture will be implemented and tested. The work will be performed by a highlyinterdisciplinary team with complementary expertise and a track-record of co-publications. PI Salaitainvented the Rolosense technology and has past experience in developing cell phone diagnostics andsynthetic motors. Co-I Melikian is an expert virologist, Co-I Heemstra is an expert at developingaptamers for novel targets, Co-I Ke has extensive experience in DNA origami structures for avid targetbinding and has co-authored work on Rolosense, Co-I Rajaraman and Primordia are experts atmicrofluidic device development and commercialization. Our solution offers the potential to provide animmediate solution to today's urgent virus sensing and tracing needs.",2020,2022,Emory University,449696,Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C09576,1R61HD105613-01,Identifying biomarker signatures of prognostic value for Multisystem Inflammatory Syndrome in Children (MIS-C),"PROJECT SUMMARY / ABSTRACTIn adults, SARS-CoV-2 infection exhibits a wide range of clinical outcomes, from asymptomatic and mild diseaseto severe viral pneumonia, respiratory distress, acute kidney injury, thrombotic disorders, and serious cardiac,cerebrovascular and vascular complications. Severe infection can also occur both in children and young adults(< 21), and a significant proportion of children admitted with Covid-19 require ICU support, frequently includingmechanical ventilation. In addition, children and adolescents with initially asymptomatic SARS-CoV-2 infectionhave presented with a rare, but very severe multisystem inflammatory syndrome (MIS-C). Epidemiologic, clinicaland laboratory predictors of progression towards severe forms of acute infection with SARS-CoV-2 and MIS-Care thus urgently needed in the fight against Covid-19 in this population. As defined in the NIH RapidAcceleration of Diagnostics (RADx) program, biomarker discovery can enable risk stratification and guideinterventional studies to target Covid-19 patients at enhanced risk of developing complications and/or severedisease. To target this discovery initiative, herein we will use a battery of biological, immunological and moleculartests, including Grating-Coupled Fluorescence Plasmonic (GCFP) and advanced flow cytometry, to studychildren and young adults (<21 years) with mild, moderate or severe SARS-CoV-2 infection. GCFP allows theuse of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format togreatly increase multiplexing capabilities. In addition, we will use a similar biomarker approach for rapiddifferentiation of patients with MIS-C versus other pediatric infectious or inflammatory conditions where theclinical presentation resembles MIS-C, most importantly Kawasaki disease. A child's biologic and immunologicresponse to SARS-CoV-2 exposure is likely influenced by a variety of factors, including genetics, epigeneticsand products of the mucosa/gut-brain axis, adipose tissue and neuroendocrine immune network, and furthermodulated by environmental exposures. With these factors in mind, we hypothesize that a child's biomarkerprofile in response to SARS-CoV-2 infection enables a timely and accurate prediction of severity of Covid-19and diagnosis of MIS-C, and will help guide treatment strategies, and predict patient outcomes. To test thishypothesis, we will use a non-traditional diagnostic and comprehensive biomarker discovery to characterize theclinical and laboratory spectrum of children and adolescents with mild, moderate and severe SARS-CoV-2infection, as well as MIS-C. We will then validate our newly developed diagnostic and prognostic algorithm todistinguish MIS-C from other inflammatory disorders with overlapping clinical manifestations, including Kawasakidisease, and predict the longitudinal risk of complications.",2020,2022,Connecticut Children'S Medical Center,877921,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +C09577,3R01MD013769-02S1,Bridging the evidence-to-practice gap: Evaluating practice facilitation as a strategy to accelerate translation of a systems-level adherence intervention into safety net practices,"ABSTRACTCOVID-19 has shed light on the significant and long-standing disparities in underserved communities. Current data still show hospitalization rates among Black and Latinx individuals in the United States are 4 times greaterthan that of Whites. The Rapid Acceleration of Diagnostics for Underserved Populations (RADx-UP) initiativesupports supplements to individual NIH awards to identify the determinants of COVID-19 testing amongunderserved populations. For this proposal, we will leverage the infrastructure of a NIMHD-funded project in theFamily Health Centers (FHCs) of NYU Langone Health, a network of federally qualified health centers in NYCthat serves over 125,000 low-income and racially and ethnically diverse patients. In the current application, wepropose a three-phase community-engaged study that will employ a multipronged, sequential mixed methodsdesign (i.e., one methodology builds on the findings of the other) to gain a comprehensive understanding of themultilevel factors that drive uptake of testing (and future vaccination) for COVID-19 of Black and Latinx patients(primary outcome), and participation in follow-up care offered by safety-net health systems. Phase 1 will consistof three steps: In step 1, we will leverage a well-characterized electronic health record database (~75% Blackand Latinx) to examine differences in the individual-level factors associated with receiving a positive versusnegative PCR test for COVID-19 among 400 Black and Latinx patients who receive care at the FHCs. We willalso capture the community- and structural-level determinants of testing in this sample using validated self-reportmeasures (e.g., NIH PhenX Tool Kit). In step 2, we will compare these multilevel factors across three patientgroups: Group 1- patients who tested positive and received follow-up care and/or services; Group 2- patientswho tested positive but did not receive follow-up care and/or services; and Group 3- patients who were eligiblefor testing (based on symptoms and probable exposure), but did not get tested. In step 3, we will employpredictive modeling to correctly identify patients at high-risk (group 3). In Phase 2, we will combine data fromthe previous phase with qualitative data (i.e., ethnographic observations, document analyses, and focus groupswith FHC staff, providers, administrators, patients and community members) to capture organizational (e.g., FHCstaff/provider attitudes and communications with patients, organizational culture) and ethical issues (e.g., datatransparency and privacy) to shed light on important social, cultural, and contextual factors associated withuptake of COVID-19 testing and potential vaccine. Finally, in Phase 3, in collaboration with our CommunityOversight Task Force, we will integrate Phase 1 and 2 data to refine, test, and disseminate tailored toolkits andethical governance guidelines (e.g. clinical trials transparency and data privacy). These toolkits will be designedto increase knowledge and awareness of COVID-19 testing and vaccine research and will be widelydisseminated among the FHCs, local community, NYULH, and the RADx-UP Coordination and Data CollectionCenter.",2020,2022,New York University School Of Medicine,152467,Human Populations | Other,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Research to inform ethical issues | Policies for public health, disease control & community resilience","Immunity | Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Communication",2019 +C09578,1R61HD105610-01,Severity Predictors Integrating salivary Transcriptomics and proteomics with Multi neural network Intelligence in SARS-CoV2 infection in Children (SPITS MISC),"AbstractChildren have been disproportionately less impacted by the Corona Virus Disease 2019 (COVID-19) causedby the Severe Acute Respiratory Syndrome Corona Virus 2 (SAR-CoV-2) compared to adults. However,severe illnesses including Multisystem Inflammatory Syndrome (MIS-C) and respiratory failure have occurredin a small proportion of children with SARS-CoV-2 infection. Nearly 80% of children with MIS-C are critically illwith a 2-4% mortality rate. Currently there are no modalities to characterize the spectrum of disease severityand predict which child with SARS-CoV-2 exposure will likely develop severe illness including MIS-C. Thusthere is an urgent need to develop a diagnostic modality to distinguish the varying phenotypes of disease andrisk stratify disease. The epigenetic changes in microRNA (miRNA) profiles that occur due to an infection canimpact disease severity by altering immune response and cytokine regulation which may be detected in bodyfluids including saliva. Our long-term goal is to improve outcomes of children with SARS-CoV-2 by earlyidentification and treatment of those at risk for severe illness. Our central hypothesis is that a model thatintegrates salivary biomarkers with social and clinical determinants of health will predict disease severity inchildren with SARS-CoV-2 infection. The central hypothesis will be pursued through phased four specific aims.The first two aims will be pursued during the R61 phase and include: 1) Define and compare the salivarymolecular host response in children with varying phenotypes (severe and non severe) SARS-CoV-2 infectionsand 2) Develop and validate a sensitive and specific model to predict severe SARS-CoV-2 illness in children.During the R33 phase we will pursue the following two aims: 3) Develop a portable, rapid device that quantifiessalivary miRNAs with comparable accuracy to predicate technology (qRT-PCR), and 4) Develop an artificialintelligence (AI) assisted cloud and mobile system for early recognition of severe SARS-CoV-2 infection inchildren. We will pursue the above aims using an innovative combination of salivaomics and bioinformatics,analytic techniques of AI and clinical informatics. The proposed research is significant because development ofa sensitive model to risk stratify disease is expected to improve outcomes of children with severe SARS-CoV-2infection via early recognition and timely intervention. The proximate expected outcome of this proposal isbetter understanding of the epigenetic regulation of host immune response to the viral infection which weexpect to lead to personalized therapy in the future. The results will have a positive impact immediately as itwill lead to the creation of patient profiles based on individual risk factors which can enable early identificationof severe disease and appropriate resource allocation during the pandemic.",2020,2022,Central Michigan University,735449,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Immunity | Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +C09579,3R01DA041243-05S2,"Exploring barriers and facilitators to women who use drugs (WWUD) awareness, acceptance and uptake of COVID-19 testing, the CARE study.","Project Summary In the U.S. women who use illicit drugs (WWUD) have disproportionately high rates of infectious(e.g., HIV, HCV), chronic, and pulmonary diseases that elevate their risk for COVID-19. Their health anddisease profile is driven by enduring social conditions (e.g., scarcity of income, food insecurity, access tohealth services, housing, discrimination). These prevailing social conditions can also undermine WWUDs'ability to protect themselves from COVID-19 (e.g., washing hands, social distancing). Drug procurementand use, which are largely social processes, further challenge these self-protection measures. Testingand future vaccination is vital to reducing COVID-19 among this high-risk population, necessitatingaccessible testing schemes. We propose a mixed methods study that draws upon the AndersenBehavioral Model10 and is grounded in eco-social theory. Specifically, the Baltimore-based study aims to:1) explore predisposing social factors (e.g., housing, food security), individual-level factors (e.g., drug use,mental health), and beliefs (e.g., medical mistrust) that are facilitators and barriers of COVID-19 testingand perceived risks (e.g., income generation, violence) resulting from a diagnosis through in-depthinterviews among WWUD (N=15) and a cultural domain analysis (N=45); 2) gain an understanding of theenabling community-level environment (e.g., medical and social service agencies that currently serveWWUD, existing city-wide COVID-19 testing sites) that could facilitate or hinder WWUDs' COVID-testinguptake through observations (N=8-10) and key informant interviews (N=10); and examine predisposingsocial factors, individual-level factors, and beliefs that are associated with COVID-19 testing and retestingamong a cohort (N=250) of WWUD at baseline and 3-month follow-up. Optional testing offered at bothstudy visits will be a self-administered, rapid antigen test. We will also examine the role of medicalmistrust in shaping women's use of healthcare services as well as experiences of stigma anddiscrimination in healthcare settings, particularly among Black participants. In Baltimore, this mistrust isparticularly pronounced, with Johns Hopkins Hospital having a long history of mistrust in the Blackcommunity owing to experimentation and deception of research engagement. The study will be guided bya community advisory board (CAB) who will inform its design and implementation as well as engage indisseminating the results at community meetings to inform COVID-testing scale up.",2020,2021,Johns Hopkins University,654592,Human Populations,Black | Unspecified,Adults (18 and older),Unspecified,Drug users | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09580,1R01MD016526-01,Marshallese: Alternate Surveillance for COVID-19 in a Unique Population,"ABSTRACT Marshallese Pacific Islanders bear a disproportionate burden of COVID-19 infection, hospitalization, anddeath, with rates 4 to 25 times higher than those of other US racial and ethnic groups in the Continental US.2,3For example, in Northwest Arkansas Marshallese people represent less than 3% of the total population, butthey account for 1 out of 5 COVID-19 cases in this area.2 Similarly, Marshallese represent just 1% of thepopulation in Spokane County, Washington, but were nearly 30% of COVID-19 cases between March andMay, 2020.4 Social determinants of health have powerful influences on community and individual risks forCOVID-19.18 Culturally, the Marshallese community is extremely tight-knit, self-contained, and highly clustered;they often live in multi-generational households; and they traditionally value close contact and large socialevents, all of which increase vulnerability to the COVID-19 pandemic.19,20Marshallese are important recipientsof effective surveillance efforts given the disproportionate impact of COVID-19 on this population and the long-standing disparities in health and health care. The MASC-UP study will generate novel data that reflect variation in risk of COVID-19 infection based onone's place in the highly clustered Marshallese community. For Specific Aim 1, bilingual MarshalleseCommunity Health Workers will recruit and train a longitudinal cohort of 800 Marshallese adults, ages 18 andolder, in participatory disease surveillance methods that include using a wireless thermometer to continuouslytrack body temperature; social media and text messaging in which participants (aka citizen scientists) canreport symptoms; and a CHW helpline to report symptoms and request COVID-19 information. Participatorydisease surveillance complements traditional surveillance systems by engaging communities in reportingCOVID-19 symptoms and events. Its strengths lie in the speed at which data can be made available, the abilityto scale the technology to obtain data at low cost, and the ability to cover populations that might not otherwisebe tracked. For Specific Aim 2 participants will complete an ego-centric contact survey to characterize thesocial contact networks of members in the disease surveillance cohort from Aim 1. The networks will allowidentification of people at highest risk of COVID-19 infection and elucidate targets for high-impact preventiveintervention. For Specific Aim 3 we will integrate findings from Aims 1 and 2 into the existing test-baseddisease surveillance currently being performed at the state and local levels. This Aim will augment existingsurveillance systems that have proved insufficient to stem the pandemic in Marshallese people. The proposedstudy will be generalizable to other high risk, clustered underserved populations.",2020,2023,Washington State University,722487,Human Populations,Other,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Restriction measures to prevent secondary transmission in communities | Community engagement,2020 +C09581,1R01NR020105-01,Multi-Modal Wireless COVID Monitoring & Infection Alerts for Concentrated Populations,"Multi-Modal Wireless COVID Monitoring & Infection Alerts for Concentrated PopulationsAbstract: The high aerosolized transmissibility of COVID, long asymptomatic incubation period,and highly variable presentation attributes of the COVID pandemic have proven challenging inmany settings where patchwork pandemic responses have disproportionately negativelyimpacted vulnerable socioeconomic, minority, and disabled sub-populations. Unfortunately, thesedire trends are only made more acute in settings that feature populations with limited mobility andlittle to no ability to self-isolate (dense concentrated populations [DCPs]), such as residentialnursing homes, schools, drug rehabilitation services, prison and psychiatric facility populations,and high-frequency essential medical services, such as chemotherapy infusion clinics or dialysisunits. In these DCP settings, limited diagnostic testing, prolonged indoor contact, limitations incleaning and filtration capacities, support staff shortages, pre-existing comorbidities, and lack ofeffective infectious disease surveillance systems all collude to drive an increased COVID burdenin DCPs. From this, it is clear that alternative detection strategies for DCPs are urgently neededto improve local capacity to monitor COVID outbreaks, mitigate their spread, and thus reduceinequitable disease and mortality burdens in these under-resourced and often overcrowdedsettings. In previous work, we developed a first generation detection system using heart rate datafrom commercially-available Fitbit Ionic wearable devices to detect the onset of COVID and otherinfectious diseases up to 10 days before users self-reported symptom onset (overall sensitivity67% prior to symptom onset). Here, we propose to further develop this system for the improveddetection of COVID and other infectious diseases in DCPs using existing wearable fitness devicesin a wireless and interoperable digital health framework that centralizes all wearable-derived dataon PHD while tailoring its presentation and health event alert system to the IT capabilities andneeds of each DCP setting. In this, not only will we adapt our existing infection detectionalgorithms for each DCP's particular baseline characteristics, IT infrastructure, and needs, butalso use incoming data to further optimize the performance of those algorithms for continuousimprovement in the sensitivity, specificity, and alert lead time for COVID onset. This will quicklyenable under-resourced DCP support staff to access and use world-class COVID surveillancedata in identifying individual infection events, implementing isolation, cleaning, and testingpolicies, and minimizing transmission, thus reducing the burden of COVID in DCP settings andreducing DCP morbidity and mortality overall.",2020,2023,Stanford University,1121730,Human Populations | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health | Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2020 +C09582,1U01DA053941-01,Development and Proof-of-Concept Implementation of the South Florida Miami RADx-rad SARS-CoV-2 Wastewater-Based Surveillance Infrastructure,"PROJECT SUMMARYThe University of Miami (UM), with three primary campuses in Miami, Florida, is geographically spread withinone of the worst current COVID-19 hotbeds. UM has deployed an elaborate human surveillance testing, trackingand tracing (3T) system to monitor the student body, faculty, and staff. This 3T system includes a major hospitalthat is part of UM and that treats COVID-19 patients. To augment this COVID-19 monitoring system, UM hasdeployed a pilot wastewater surveillance program for detecting SARS-CoV-2 from clusters of buildings oncampus. Weill Cornell Medicine (WCM) is located in New York City, NY, an area that until recently had one ofthe worst outbreaks of COVID-19. WCM has established an international consortium for SARS-CoV-2environmental surveillance, including in NYC and globally with the MetaSUB Consortium, which is creatingmetagenomic and metatranscriptomic maps of the world's sewage. Based on this work at both UM and WCM,this proposal aims to develop, implement, and demonstrate effective and predictive wastewater surveillance byoptimizing sampling, concentration, and detection strategies. Working closely with the RADx-rad DataCoordination Center (DCC), this application (SF-RAD) will develop and implement data standards andinformatics infrastructure and perform integrative analyses to make all data, results, and models available to thecommunity, thus providing a critical contribution to the national SARS-COV-2 RADx-rad Wastewater DetectionConsortium. Our objectives will be addressed through three aims. Aim 1: Data Standardization, focuses ondeveloping and implementing data standards and quality metrics, and establishing the operational infrastructureto manage SARS-CoV-2 wastewater-based surveillance datasets and metadata. Aim 2: WastewaterCharacterization, focuses on optimizing wastewater surveillance protocols and parameters for wastewatersampling, sample concentration, and viral detection technologies. Aim 3: Integration with Human HealthSurveillance, focuses on metatranscriptomic analyses and on the integration of wastewater quantification datawith community and hospital COVID-19 prevalence, to develop predictive models to detect local and communitylevel spread of COVID-19. All data will be made Findable, Accessible, Interoperable and Reusable (FAIR) inclose collaboration with the DCC, and will be collected and managed with attention to ethical issues insurveillance and data management, including efforts to ensure research rigor and reproducibility. The resultsfrom this proposal will develop and deploy experimental and informatics infrastructure and operations as part ofthe national RADx-rad SARS-CoV-2 wastewater surveillance network and will provide a proof-of-conceptimplementation to use wastewater for infectious disease surveillance for early detection of localized COVID-19outbreaks.",2020,2022,University of Miami Coral Gables,2676864,Environment | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2021 +C09583,1R21AI159323-01,Novel small-molecule inhibitors of SARS-CoV-2 protease,"The overall objective of this project is to use a combination of medicinal chemistry, X-ray crystallography,biochemical and biological activity testing to develop potent, drug-like inhibitors of the main protease (Mpro) ofSARS-CoV-2 (SARS-2), a novel coronavirus that causes an outbreak of a serious pulmonary disease COVID-19 (coronavirus disease 2019). SARS-2 has emerged in Wuhan, China and soon spread to >210 countriesworldwide. WHO has declared COVID-19 a global pandemic in March 11, 2020. As of early June, SARS-2 hasinfected ~7 million people (confirmed cases) globally, including ~2 million cases in the US. These numbers arerapidly growing everyday. SARS-2 is highly contagious. While most patients (81%) infected with SARS-2 showrelatively mild symptoms, life-threatening severe illness, including severe pneumonia, sepsis and organ failure,can occur at a significantly higher risk for people at age of ≥65 years and people with serious underlyingmedical conditions. SARS-2 has caused ~400,000 deaths globally including >110,000 in the US (as of earlyJune, 2020), which makes it one of the most dangerous pathogens in modern history. There is therefore apressing need to find effective therapeutics and vaccines for SARS-2 infection. The main protease (Mpro) ofSARS-2 is essential for the viral replication and therefore a drug target. Specific Aim 1 is to use ration inhibitordesign, medicinal chemistry and structure-activity relationship (SAR) studies to find more potent inhibitors ofSARS-2 Mpro. Specific Aim 2 is to perform enzyme inhibition, X-ray crystallographic and otherbiochemical/physical studies to characterize compounds made in Aim 1, which will be used to guide rationaldesign and SAR studies in Aim 1 to find compounds with improved potency. Specific Aim 3 is to performcytotoxicity and cellular antiviral activity testing of selected potent inhibitors of SARS-2 Mpro, in order to findnon-cytotoxic, potent antiviral compound against SARS-2 and -1 infections. Success of this pilot project wouldlead to small-molecule inhibitors with improved potency that can strongly inhibit SARS-2 replication. Inaddition, X-ray crystallography and other biochemical/physical studies would reveal the inhibitor-Mprointeractions. These compounds would serve as novel pharmacological leads for further drug developmenttargeting SARS-2 and other coronavirus infection.",2020,2022,Baylor College Of Medicine,440000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C09584,3U01GM132175-02S1,Keeping rural minority 'essential' workplaces open safely during the COVID-19 pandemic: The role of frequent point-of-care molecular workplace surveillance for miners,"ABSTRACTThere are limited studies on the spread of SARS-CoV-2 infection in rural essential workers. This gap-in-knowledge mustbe addressed to develop and implement novel pandemic strategies to keep open rural essential workplaces, such as coalmines. The long-term goal of the study is to mitigate the spread of the pandemic in miners, a population of high-risk, ruralessential workers who are susceptible and vulnerable to COVID-19, and who are predominantly racial/ethnic minorities inNew Mexico (NM). The study objective is to provide proof-of-principle for frequent point-of-care molecular testing as aworkplace surveillance tool to monitor and prevent the spread of SARS-CoV-2 infection in this unique population. Thecentral hypothesis is that frequent workplace molecular surveillance is an effective method to reduce SARS-CoV-2 infectionand discover novel host risk factors. The site of molecular surveillance (intervention site) will be a surface mine in McKinleyCounty, NM, located just outside the Navajo Nation, comprised of 66% minority miners. Miners at the intervention site willprovide nasal swabs every alternate work shift, which will be analyzed with the Abbott ID Now™ COVID-19 test, i.e., the'index' test. The control mine located at Campbell County, Wyoming, has similar mine characteristics as the interventionmine. The rationale for this study is to establish the suitability of longitudinal molecular surveillance to prevent and controlSARS-CoV-2 infection in this unique population by completing the following aims. Specific Aim 1: To determine theacceptance rate to frequent point-of-care molecular workplace surveillance among miners. Hypothesis 1: Miners will havea cumulative acceptance rate of frequent testing at ≥85%, with the added objective of exploring difference in acceptance byminer characteristics. Specific Aim 2: To determine the ability to detect the presence of SARS-CoV-2 by point-of-caremolecular workplace surveillance in a real-world setting of miners. Hypothesis 2: The sensitivity of the index test in a real-world study setting is a) comparable to that described by others in controlled settings, and b) positively associated with viralload in upper respiratory specimens. Specific Aim 3: To determine the effectiveness and implementation costs of frequentpoint-of-care molecular workplace surveillance on reducing incident infection rates of SARS-CoV-2. Hypothesis 3A:Frequent point-of-care molecular testing over six months in the intervention mine will result in lower incident seropositivityrates compared to the control mine. Hypothesis 3B: Frequent point-of-care molecular surveillance in the intervention mineis cost-effective compared to the control mine. Specific Aim 4: To determine novel predictive host factors associated withincident SARS-CoV-2 infection in miners. Hypothesis 4: Miners with incident infection demonstrate less frequent use ofcloth face coverings outside the workplace, greater mine dust exposure intensity, presence of dust-related lung disease, andracial/ethnic minority status than those not infected. Successful completion of the study will establish the acceptability andeffectiveness of the proposed surveillance in work settings where common occupational mitigation strategies are notpossible. Findings from this study will provide broad-reaching implications for novel pandemic strategies to keep ruralessential workplaces open. By working with the NIH RADx-UP Coordinating and Data Collection Center, this study willprovide crucial data for subsequent studies of vaccine interventions in rural minority essential workers.",2020,2024,University Of New Mexico Health Scis Ctr,958041,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience","Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions",2020 +C09585,3U54MD007597-32S2,Howard University Research Center for Minority Health and Health Disparities,"PROJECT ABSTRACTCenters for Disease Control data continue to show that, in unadjusted analyses, Non-Hispanic Blacks, IndigenousAmericans and Hispanic and Latino persons have higher COVID-19 case rates, hospitalizations, and deaths compared toNon-Hispanic Whites. The observed differences in morbidity and mortality do not appear to be adequately explained bypre-existing risk factors. It is becoming widely accepted that COVID-19 disparities are, in large part, a direct result ofstructural violence; defined as the built in differences in distribution of resources, education and literacy, medical care,social and economic opportunities, and, importantly, power to decide. In keeping with recommendations that pandemicresponse planning and readiness should include addressing social injustice, the proposed study seeks to lay a foundationfor a long-term response to the social determinants of health disparities that have been laid bare by COVID-19. Thepopulation of interest for this study are African Americans in the DC metropolitan area with an emphasis on communitiesthat experience social, economic, and health vulnerabilities. To achieve our aims, we have convened a broad-based groupof diverse scholars, health professionals, and community stakeholders. This group will collaboratively create and curatean information repository that will be used to create strategies to guide interventions to address the current crisis, with alens toward long-term change. We will test two specific interventions; both designed to increase research literacy andpromote community capacity for informed decision making about COVID-19 response behaviors including participationin testing, clinical research, and vaccination. We hypothesize that messages that emphasize informed choice will promotemore favorable attitudes toward COVID-19 research and vaccination. The first intervention approach will conveneopportunities for researchers and community members to have frank dialogues about the quality and relevance ofemerging science and the unique ethical challenges presented by the pandemic. The second intervention will applyevidence-based community health work interventions to address community information needs about COVID-19. Thesecommunity health interventions will also be responsive to everyday health and social priorities that might take precedenceover considerations of adhering to recommendations for COVID-19 response. We anticipate that these activities willpromote trust in using research information to make informed decision because the trust is not in the expert knowledge,but in the individual's ability to weigh the evidence and draw conclusions. We anticipate that this project will result inimportant outcomes including: 1) replicable approaches for enhancing existing networks for engaging communities intesting, follow-up care and social services to address basic needs related to COVID-19; 2) creation of a trusted COVID-19communication network to reach underserved and/or vulnerable populations and 3) evidence-based materials andapproaches to address current misrepresentations or misunderstandings inhibiting uptake of COVID-19 testing andvaccination.",2020,2022,Howard University,193751,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,1997 +C09586,3R01DA037628-05S1,Prevention of Substance Use in At-risk Students: A Family-centered Web Program,"PROJECT SUMMARYPeople who inject drugs (PWIDs) are a socially vulnerable population and are exposed to risk factors includingunstable housing and underlying medical conditions such as human immunodeficiency virus (HIV),tuberculosis (TB), and viral hepatitis that put them at increased risk for severe COVID-19 symptoms, includingdeath. PWIDs also experience barriers such as a history of stigmatization and discrimination by health caresystems and exposure to misinformation about testing that reduces access to health care services and testing.Because timely receipt of services relative to symptoms onset is critical for positive health outcomes and toreduce SARS-CoV-2 transmission, lack of testing has significant implications for PWID, highlighting an urgentneed to increase testing uptake among this population. Despite this, PWIDs have been an underservedpopulation in the context of the current pandemic; thus, little is known about the prevalence of COVID-19 andthe acceptability and possible reach of testing for COVID-19 among PWIDs. To address this gap, this studyleverages a current partnership with HIV Alliance (HIVA) in Oregon and our Community and Scientific AdvisoryBoard to support implementation and sustainability of a COVID-19 testing program. Specifically, we will usecommunity-based participatory approaches to develop, implement, and evaluate a COVID-19 testing programoffered through HIVA's Syringe Services Programs (SSP), a natural point of care for PWIDs. Moreover, SSPsmay offer a natural venue for dissemination and delivery of a vaccine, once available. The COVID-19 testingprogram will include procedures for sample collection, transmission of specimens to the University of OregonCLIA-certified laboratory, and results reporting. For aim 1, we will assess the testing program utilization. Foraim 2, we will develop and test a brief motivational enhancement intervention to optimize testing utilizationamong PWIDs. Using an interrupted time series design, we will evaluate intervention effects on utilization ofCOVID-19 testing resources. For aim 3, we will collect data from syringe exchange staff and key volunteers onprogram acceptability, feasibility, appropriateness, adoption, and implementation barriers and facilitatorsrelated to the testing program and intervention. The current project has the potential to enhance COVID-19testing access and reach among a significantly underserved population who experience multiple risks thatmake it difficult to prevent SARS-CoV-2 exposure and transmission and who are at increased risk for severeCOVID-19 symptoms, if they were to contract the disease.",2020,2021,University Of Oregon,1213204,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C09587,1U18TR003793-01,Microfluidic Isolation and Characterization of SARS-CoV-2 and Virus Related Exosomes,"PROJECT SUMMARYRobust, efficient and reliable testing for SARS-CoV-2 is extraordinarily challenging due to our lack of ultra-sensitive assays and ever evolving knowledge of the virus. Standard PCR based assays still result in very highfalse negative rates in the earliest days of infection. Microfluidic processing of clinical samples is low cost andshows great promise for translating most liquid biopsy assay to the clinic. Our laboratory was one of the first toapply microfluidic technologies for the isolation of both circulating tumor cells and exosomes in the blood ofpatients with cancer. For SARS-CoV-2 patients, saliva, stool, and plasma are all thought to be potential resourcesfor both virus detection as well as other clinical biomarkers that might inform us of infection. Thus, for this U18,we will optimize our exosome capture technology, the EVHB-Chip, for the isolation of intact SARS-CoV-2 virus,testing its utility for each of these biofluids. To complete this work, we will complete a full clinical validation andbenchmarking of the assay. Once fully optimized, our detection assay will be compared against existing EUASARS-CoV-2 detection assay to determine detection sensitivity and specificity. Further, we plan to demonstratethat the increased sensitivity and specificity enabled by our microfluidic device will result in earlier detection ofSARS-CoV-2, reducing false negatives in this testing window. At the completion of this work, we will havecollected the data training sets and submitted a full EUA plan that would enable the FDA's authorization of ourtest to be used in the clinic.",2020,2022,Massachusetts General Hospital,999860,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09588,3R37AI051652-15S1,Biomolecular Markers for Safe Minimization of Immunosuppression,"We seek additional funds for research responsive to the SARS-CoV-2/COVID-19 outbreak that is in scope ofour ongoing grant R37AI051652 ""Biomolecular Markers for Safe Minimization of Immuno-suppression."" FromMarch 13, 2020 to April 20, 2020, we hospitalized 39 kidney allograft recipients positive for SARS-CoV-2 andwith Covid-19 symptoms. Among these patients, 20 (51%) developed acute kidney injury (AKI). Importantly, graftdysfunction due to AKI recovered in 9 patients only and did not recover in 11 patients as of May 15, 2020. Noneunderwent a diagnostic allograft biopsy because of biopsy-associated complications such as bleeding arepotentially much more serious in this cohort and also to limit potential exposure of healthcare workers to SARS-CoV-2 during the invasive biopsy procedure. In the absence of a diagnostic biopsy, none received anti-rejectiontherapy. Whether the graft dysfunction was reversible or nonreversible could not be predicted at the time of graftdysfunction diagnosis. The dynamics of anti-allograft response from the reductions in their immunosuppressivetherapy could not be captured with the available clinical analytes. To address these existing challenges, wepropose the following: Specific Aim 1. To perform RNA sequencing of urinary cells and investigatewhether the urinary cell transcriptome, ascertained at the time of graft dysfunction, is prognostic ofallograft dysfunction. Urine will be collected at the time of graft dysfunction diagnosis and RNA isolated fromurinary cells. RNA from 30 patients with reversible graft dysfunction; RNA from 30 patients with nonreversiblegraft dysfunction; and RNA from 30 patients with no graft dysfunction during the 3 months since Covid-19diagnosis will be RNA sequenced and bioinformatics performed. The goal is to determine whether the urinarycell transcriptome profile, ascertained at the time of graft dysfunction, is prognostic of graft dysfunction anddistinguishes those with reversible graft dysfunction from those with nonreversible graft dysfunction. SpecificAim 2. To measure urinary cell 3-gene signature score in sequential urine samples from Covid-19 kidneyallograft recipients. Urine will be collected at baseline and sequentially every two weeks for 3 months sinceCovid-19 diagnosis. We will retrieve 210 sequential samples from 30 Covid-19 kidney allograft recipients(Baseline and 6 sequential samples from each patient) who developed reversible graft dysfunction; 210sequential samples from 30 Covid-19 kidney allograft recipients who developed nonreversible graft dysfunction;and 30 Covid-19 kidney allograft recipients who did not develop graft dysfunction during the 3-months sinceCovid-19 diagnosis. RNA isolated from urinary cells will be reverse transcribed to cDNA and absolute copynumbers of CD3E mRNA, CXCL10 mRNA and 18S rRNA will be measured using customized PCR assays andurinary cell 3-gene signature score will be computed using a validated regression equation. The objective isto determine whether the urinary cell 3-gene scores in sequential samples anticipate those who developnonreversible graft dysfunction rom those who develop reversible graft dysfunction.",2021,2021,Weill Cornell Medicine - Cornell University,374941,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity",2021 +C09589,1U01DC019579-01,Longitudinal At Home Smell Testing to Detect Infection by SARS-CoV-2,"Abstract:Self-report of sudden loss of smell or taste substantially increases the odds of being infected with SARS-CoV-2(10 - 37-fold). However, self-report of smell function is an unreliable predictor of smell loss. Based on ourexperience developing smell tests with personalized algorithms for asymptomatic detection of Alzheimer'sdisease, we created a self-administered easy to use ""at home"" 5-minute objective smell test to uncoveralterations in smell function unbeknownst to many individuals, and confer increased risk of infection by SARS-CoV-2. Our new smell test consists of a physical smell card containing peel and sniff odor labels and a web-based application. The disposable smell card reduces the risk that the smell test serves as a vector oftransmission to other patients, research staff, and to health care workers. Each participant accesses the web-based app on their own smartphone, tablet, or computer. In our pilot studies, we validated each participant'sCOVID status by extracting results of clinical SARS-CoV-2 RT PCR assays from electronic health records. Thesmell test provides better area under the curve for SARS-CoV-2 infection (0.83 - 0.85) in both US andArgentinian symptomatic patients (ages 19 - 87) than symptom tracking alone (0.66). We are expanding thesmell test from one smell card with three odors to 6 smell cards, each with 3 different odors (18 odors total).Having six different versions of the smell card will afford longitudinal screening several times per week andprovide data to construct personalized thresholds for changes in olfactory function - each person serving astheir own control and monitoring for diminishment of their expected performance based on their personaltrajectory rather than being based on population norms. Here we propose to develop a native app to conductlongitudinal COVID Smell Test (Aim 1), collect data on asymptomatic health care workers, symptomaticpatients, and undergraduates (Aim 2) and develop algorithms for the longitudinal smell test for personalizedthresholds, differentiate smell loss from COVID relative to influenza, and assess risk of developing pulmonarydisease in COVID infected patients (Aim 3). The Longitudinal COVID Smell Test is accessible, affordable, andreadily scalable. Effective screening with the COVID smell test will better inform students and employees ifthey should not report to school or work, and seek an evaluation by a healthcare professional and moleculartesting at an early, often asymptomatic, stage of the disease.",2021,2022,"Adk Group, Llc",877288,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Digital Health,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09590,3P41EB015898-15S1,Image Guided Therapy Center - Ultrasound-based sensor system for the monitoring of COVID-19 patients,"Project summaryThere are currently ~1.8 million active cases of COVID-19 in the US. Most of these patients are recovering athome, creating immense needs for remote monitoring. The main tools currently available for the task arethermometers, pulse oximeters and spirometers, to monitor temperature, blood oxygen level and lung capacity,respectively. We developed an ultrasound-based sensor system that captures in rich manner the way in whichpeople breathe, and we believe that such biomechanical information can be an important complement to other,currently available tools. The proposed project involves modifying the hardware and software of our currentsensor system to make it compatible with home-based monitoring, more specifically by making it smaller,wireless, cloud-based and inexpensive.Pulse oximeters and spirometers are closely related to the proposed sensor system in that they offer ameasure of lung health. Spirometers provide a single measurement for the entire respiratory system, i.e., thevolume of air exhaled. Because it is a device that one blows air into, it readily becomes contaminated whenused by COVID-19 patients. Pulse oximeters are very helpful in the sense that they measure a parameter atthe core of lung function, i.e., the ability to convert deoxyhemoglobins into oxyhemoglobins. For spirometersand pulse oximeters, normal or highly abnormal readings fulfill the purpose of a home-based monitoring devicein the sense that they lead to clear decision making when the options are primarily 'remaining at home' vs.'hospital admission'. Intermediate readings, however, can be more difficult to interpret. Especially as treatmentoptions continue to increase and diversify, more data will be needed to inform decisions, and biomechanicalinformation as provided by our sensors is expected to be a valuable addition. By better informing decisions onpatient management, it is easy to appreciate how the proposed sensor system might very well have life-savingeffects in given patients.We propose to develop a rapid home-based testing/diagnostics device, in the form of wearable remote sensorsfor physiological monitoring. Our ultrasound-based sensors monitor tissue velocity and displacement at varioustissue depths, at up to four separate locations on the torso, and as such richly captures the biomechanicalmotion associated with breathing. The proposed project involves converting our current PC-sized system into asmaller, wireless, cloud-based and inexpensive system compatible with home-based monitoring, and todevelop algorithms specific to COVID-19 patients to better convert the rich motion information the sensorsprovide into an assessment of one's state of recovery from the disease. Preliminary results suggest feasibilitywithin one year, and a path to commercialization is presented in the proposal.",2020,2021,Brigham And Women'S Hospital,359999,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C09591,3R01DC016112-04S1,A confectionary-based screening tool for assessing chemosensory loss in COVID 19 patients.,"The goals of this Emergency Competitive Revision are to develop (Aim 1) and deploy (Aim 2) anovel, objective, psychophysical smell and taste screening test to detect the onset of COVID 19in at-risk populations. Complementary to the temperature screening procedures currently in use,this tool is predicted to promote early identification of COVID onset leading to better prognosesand the early implementation of protocols to prevent community spread. Our specific plan is touse a hard-candy containing different combinations of tastants and flavors that are easy todistribute to a large population. During the development phase (Aim 1), this novel test will becompared with the NIH toolbox to assess the acceptability and efficacy of the two methods. Weexpect that the hard-candy assessment will be at least as efficacious in detecting chemosensoryloss but more acceptable to subjects. Aim 2 will entail daily self-monitoring of chemosensoryfunction in at-risk populations with data tracked through a secure online portal. The novelty ofthis confectionary-based test is that it provides standard stimuli that can yield objectivemeasures of both the qualitative and quantitative aspects of smell (aroma and flavor) and taste(sweet and sour). Moreover, both orthonasal and retronasal olfactory function will beindependently assessed. The test can be self-administered and the familiar, pleasant nature ofthe stimuli should facilitate a high compliance rate, allowing for continuous monitoring overprolonged periods. Moreover, the test is rapid and inexpensive. Data will be incorporated into apredictive model for COVID 19 and assessed using AOC analyses of sensitivity and specificity.OSU is a leading large public land grant university with a varied population of students, faculty,and support staff that includes all health care specialties. These characteristics, along with theUniversity-mandated regular PCR testing of students and staff makes it a perfect site to performthis urgent research.",2020,2021,Ohio State University,305085,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09592,3R01DA036749-05S1,Getting Asian Americans INFORMED to Facilitate COVID-19 Testing and Vaccination,"PROJECT SUMMARYThis time sensitive proposal, Getting Asian Americans INFORMED to Facilitate COVID-19 Testing andVaccinations, is to identify and address sociocultural, ethical and behavioral barriers related to COVID-19testing and vaccination to enable Asian Americans to make well-informed decisions about getting tested forCOVID-19. Asian Americans have experienced among the highest COVID-19 mortality rates when measuredin case fatality and proportionate mortality due to COVID-19. Excess COVID-19 related deaths observed inAsian Americans are in part due to under-testing. Asian Americans may face multiple challenges, includingsociocultural (limited English proficiency, lack of trust, excess fears and social stigma related COVID-19),ethical (lack of proven benefits of various guidelines, unequal access to testing resources), and behavioral(tobacco and e-cigarette use, other competitive behaviors) factors. The pandemic is rapidly evolving andpresents urgent needs to develop highly efficient channels to communicate accurate, easily comprehensive,cultural appropriate and practical information. This application is a supplement to a parent R01 ""A Family-Focused Intervention for Asian American Male Smokers,"" as known to the public as a community-basedintervention research program ""Healthy Family Project."" The Healthy Family Project has provided more than1,100 smokers and families a family-oriented intervention delivered by lay health workers (LHW) showingefficacies in in reducing tobacco use and promoting healthy nutrition and physical activity among Chinese andVietnamese Americans. Prior to the parent R01, our team tested LHW interventions targeting individualbehavior change in increasing colorectal, cervical and breast cancer screening and hepatitis B and C testing,and healthy nutrition and physical activity among Chinese, Hmong, Korean, Filipino and VietnameseAmericans. Leveraging the community partnerships and the individual / family-based LHW interventionapproaches that we developed, we propose these aims: (1) Develop and evaluate ""INdividual and Family-Oriented Responsive Messaging EDucation"" (INFORMED) intervention in increasing knowledge about COVID-19 testing and decreasing decisional conflicts of getting tested for COVID-19. A 2-arm randomized controlledtrial will compare INFORMED delivered by LHW educational outreach plus SMS text messaging to SMS textwith LHW support. (2) Conduct in-depth prospective investigation of sociocultural, ethical and behavioralfactors related to COVID-19 testing in Chinese, Hmong and Vietnamese American over-time. In addition, wewill explore factors affecting acceptance for vaccination research trial participation and vaccination uptake andhow vaccination acceptance is associated with COVID-19 testing uptake.",2020,2021,University Of California-San Francisco,589981,Human Populations,Asian | Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C09593,1U01DA053949-01,Optimizing SARS-CoV-2 wastewater based surveillance in urban and university campus settings.,"The novel coronavirus SARS-CoV-2 is causing significant morbidity and mortality. Current approaches to SARS-CoV-2 testing are costly, inconsistently implemented, and fail to rapidly identify evolving outbreaks. Innovativesurveillance programs are urgently needed to better measure baseline transmission dynamics and anticipatenew localized outbreaks. Wastewater based testing (WBT) has the potential to enable population levelsurveillance, trigger earlier regional responses to acute outbreaks, and overcome barriers to individual testingsuch as stigma and lack of access. WBT could therefore enable faster and cheaper pathogen detection andimprove population-level estimates of prevalence. Reliable capture approaches for this novel coronavirus usingWBT are currently undefined. Viral dynamics during wastewater transport must be considered, and correlationof WBT with clinical testing must be systematically evaluated at multiple scales. Here, we propose to optimizeWBT surveillance protocols of waste streams at an urban university campus encompassing dorms, researchfacilities and a tertiary care hospital, surrounding sewershed and wastewater treatment plant. We will detectSARS-CoV-2 using qRT-PCR to estimate prevalence and viral panel-enriched metatranscriptomics tocharacterize viral diversity. We will model case counts using normalized WBT data and develop point-of-usemicrofluidics systems for WBT. Our team of investigators is uniquely positioned for this study, with expertise ininfectious diseases, epidemiology, microbial characterization using WBT at national scales, and point-of-caretesting. We will implement three complimentary specific aims. In Aim 1, we will optimize (1a) collection andprocessing to determine sensitivity and safety of WBT. This includes grab vs. composite sampling;) filtration- vs.precipitation-based enrichment; and viral inactivation protocols. We will further optimize scale and frequency ofsampling (1b) at the building/sewer pit, campus, sewershed, and WWTP, and across various frequencies.Presence of SARS-CoV-2 will be ascertained by qRT-PCR and long-read spiked-primer enrichedmetatranscriptomics. WBT results will be integrated with clinical case-loads, existing surveillance cohorts andexpanded employee surveillance. In Aim 2. we will improve modeling of SARS-CoV-2 case dynamics usingextrapolated WBT data and site-specific normalization factors. We will correlate modeled building-, campus- andcommunity-level case counts with existing clinical incidence data and campus surveillance using ensembleKalman filter (EnKF) dynamic modeling incorporating both qRT-PCR and metatranscriptomics data. We willcompare normalization methods factoring in wastewater residence time, per capita viral load equivalents(PCVLEs), and other waste flow parameters to reduce model error. Finally, in Aim 3, we will adapt point-of-usetesting capabilities using microfluidics based on optimized WBT protocols. We will apply existing RADxdevelopment of a photothermal amplification system for SARS-CoV-2 detection to optimized WBT practices. Wewill develop a modular system for WBT samples and determine assay detection thresholds using viral controls.",2020,2022,Columbia University Health Sciences,2448262,Viruses | Environment | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics | Disease surveillance & mapping,2021 +C09594,1U01AA029328-01,Development of an Automated Diagnostic Platform for SARS-CoV-2 Monitoring in Vulnerable Areas,"Project SummaryThe devastation caused by emerging pathogens with fast transmission capacity, such as SARS-CoV-2, hasdemonstrated the importance of preparedness for future viral outbreaks; this includes the ability for fastdeployment of in-situ testing tools and epidemiological surveillance with high temporal and spatialresolution; particularly in places that are most vulnerable to becoming reservoirs of infectious agents.We propose to develop a versatile multiplexing detection platform for SARS-CoV-2 in saliva. The proposedsystem will integrate signals from different biorecognition elements. Aptamer, antibody, and ACE2 will beimmobilized onto laser inscribed graphene electrodes, and detection mechanisms targeting SARS-CoV-2spike protein will be studied under varying testing conditions (pH, temperature, ionic strength). Afterdetermining the operating conditions for enhanced performance of each biosensor, a self-referencingapproach will be used between complementary recognition elements (i.e., possible combinations ofaptamers, antibodies, and ACE2 enzyme biosensors) to evaluate the effects on test results accuracy (i.e.,risk of false-positive and false-negative results). A saliva pre-treatment protocol will be developed tofacilitate SARS-CoV-2 testing in human saliva using the multiplex biosensor platform. An open channelmicrofluidics system will be designed to automatically split and channel a single saliva sample into multiplestreams to the biosensors without saturation, biofouling, and pump requirement. The development of afunctional and reliable multiplex biosensor system will be useful for addressing longstanding needs in publichealth as the respiratory Coronavirus family continues its seasonal visits, which may repeat over severaldecades, much like the occasional visits from the influenza virus, with varying degrees of virulence.",2020,2022,Clemson University,471237,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09595,3UL1TR001409-06S3,GHUCCTS N3C COVID data mapping,"AbstractA major challenge to full utilization the available data and resources has been the complex nature of healthdata, and heterogeneity of data sources (including unstructured clinical notes) combined with a lack ofstandards. The lack of standards precludes semantic interoperability across platforms and between institutions.Instead, current approaches utilize resource intensive natural language processes to extract, transform, andcorrelate data from different sources for analysis. To improve translational science and accelerate research toimprove patient outcomes, many new and innovative studies are leveraging large volumes of available datathrough standardized and shared data initiatives. With current advances in computing and health data analysistools, methods and access, and to make data more meaningful, open, and accessible, research studies havemoved beyond traditional retroactive reporting to pragmatic interventions and predictive capabilities. Ongoingefforts focus on exploiting common data standards and models such as the Observational Medical OutcomesPartnership (OMOP) standard-defined by the Observational Health Data Sciences and Informatics (OHDSI)consortium, and accepted as canon by both the NIH and PCORI- will lead the way to discover insights intextual narrative, enforce data standardization, and promote scalability and sharing. The OHDSI Common DataModels (CDM) makes data more meaningful, open, and accessible, which drives translational science andallows for consistent development of predictive models across different data sources. The National COVIDCohort Collaborative (N3C), ACT, BD2K-NIH Data Commons, the National Center for Data to Health (CD2H),and others are among the efforts that will lead to new discoveries and informed decision making, driven bydata science and undergirded by mature Big Data technologies. We propose to design and establish novel,scalable, and standardized big data processes to massively abstract the raw electronic medical recorddatasets for observational studies. This project will develop a secure cloud-based environment to host thesedata, as well as the application programming and graphical user interfaces to support observational researchstudies leveraging these resources. By these means we will reduce the barriers to data standardization,annotation and sharing for reproducible analytics and begin to enforce complete semantic and syntacticinteroperability between the resources in the data ecosystem. This effort will enable our investigators to studythe effects of medical interventions and predict patients' health outcomes and generate the empirical evidencebase necessary to establish best practices in observational analysis.",2021,2021,Georgetown University,99864,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing | Innovation,,,United States of America,United States of America,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening,2015 +C09596,1R01DK130067-01,"Early detection, containment, and management of COVID-19 in dialysis facilities using multi-modal data sources","AbstractWith older age and multiple comorbidities, dialysis patients are at high risk for serious complications, even death,from COVID-19. There is a large disproportionate representation of minorities, especially Blacks and Hispanics.Over 85% of hemodialysis patients travel three times a week to dialysis facilities to receive life-sustainingtreatments and cannot shelter in place. There is a critical need to characterize COVID-19 transmission pathwaysin dialysis patients and clinics, identify potential coronavirus carriers, and develop procedures to curb the spread.With regular medical encounters, a large amount of data has been collected for each patient over time. Thesedata have not been fully utilized for COVID-19 prediction and control in dialysis clinics. In this proposal, we seekto leverage demographic, clinical, treatment, laboratory, socioeconomic, serological, metabolomic, wearable andmachine-integrated sensors, and COVID-19 surveillance data to develop mathematical and statistical modelsand implement them in a large number of dialysis clinics. The mathematical and statistical modeling usingmultiple data resources will help us understand how COVID-19 spread in dialysis facilities, identify potentialCOVID-19 patients before symptoms appear, and identify potential asymptomatic COVID-19 patients. We willdevelop novel mathematical and statistical models that fully utilize the high dimensional multimodal dataavailable to us and other dialysis providers. We capitalize on the intrinsic advantages of hemodialysis clinics toimplement and validate the proposed prediction models. We firmly believe that this cross-disciplinary effort willimprove patients' and staff's safety while delivering high-quality, individualized care to a high-risk population.",2020,2023,University Of California-Santa Barbara,652205,Human Populations | Other,Black | Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease transmission dynamics | Disease surveillance & mapping | Supportive care, processes of care and management",2020 +C09597,3R01AI145840-02S1,Progesterone induced immune modulation during pregnancy - supplemental research in COVID-19,"Project Summary: Despite pandemic spread of the novel coronavirus, COVID-19, significant knowledge gapsremain especially for Center for Disease Control designated high risk populations such as pregnant women. Ofhigh clinical importance is the susceptibility of pregnant women to infection, the direct risk to the mother and theindirect impact of disease severity (including preterm delivery and fetal death) on the pregnancy. While muchresearch is being pursued from translational research to intervention trials for COVID-19, pregnant women arealmost universally excluded from intervention and observational trials. Research in pregnant women is of thehighest priority. The ability to understand which pregnant women are at risk for severe COVID-19 disease, weeksif not months prior to clinical symptomatology, could provide novel and important windows for preventativeinterventions to limit maternal morbidity and mortality. Additionally, if clinical data emerges that the majority ofpregnant women may actually be more tolerant of SARS-CoV-2 compared to other respiratory viruses,understanding the immunological changes of pregnancy may provide insights as to ways to modulate diseaserisk in non-pregnant populations. To address all of these gaps in knowledge, large maternal cohorts withbiospecimens and detailed phenotyping in areas of high prevalence of COVID-19 are required. The establishedinvestigative team and research infrastructure for two active maternal cohorts designed for prospective analysisof maternal immunity during pregnancy (R01-A1145840) can now be leveraged to investigate deep immunephenotyping of pregnant women prior to acquisition of COVID-19. We will be able to investigate how differentimmune phenotypes predict COVID-19 infection in pregnant women. Complementing the existing expertise inperinatology and immunology for the parent RO1, this study add the immunology and virology expertise at theUniversity of Pennsylvania. We propose to investigate the following three scientifically important aims: 1) whethermaternal immune profiles are associated with acquisition and severity of COVID19 in pregnant women; 2)whether immune profiles in pregnant women with active COVID19 are similar to non-pregnant women with similardisease severity and 3) whether immune profiles in the 2nd trimester of pregnancy are associated with adversereproductive outcomes. All women enrolled will have extensive metadata collected with adjudication of COIVD-19 status and severity as well as detailed clinical phenotyping of obstetrical outcomes. Deep immunephenotyping will provide innovative and rigorous investigation of innate and adaptive immune states duringpregnancy and will be interrogated regarding their association with COVID19 phenotypes. We will alsoinvestigate the presence of maternal antibodies (IgG and IgM against SARS-CoV-2) at the same time point asimmune profiling. We have the necessary expertise, the research infrastructure and the patient population tocomplete the proposed study in the 2 year time line with a 400 person cohort. This study address many significantgaps in knowledge including essential questions regarding the immune biology in pregnancy.",2021,2023,Cincinnati Childrens Hosp Med Ctr,488752,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity,2021 +C09598,1U01DA053893-01,Wastewater Detection of COVID-19,"When faced with a pandemic such as SARS-Coronavirus-2 (SAR-CoV-2), the virus responsible for COVID-19,timely risk assessment and action are required to prevent public health impacts to entire communities.Because infected individuals may not have access to testing or may be asymptomatic and contraction canmean death, a proactive approach to detect the virus is needed to develop public health strategy to mitigatevirus spread. Recent studies have detected SAR-CoV-2 genetic material in sewage and demonstrate apositive correlation between the concentration of viral markers and reported cases1-5. The CoronavirusSewershed Surveillance Project (CSSP) is a collaborative effort to monitor sewersheds for genetic indicators ofCOVID-19 in wastewater to provide additional, population-level information about virus circulation that is notcaptured by clinical testing. Untreated wastewater (influent) samples are screened weekly from selectsewersheds and targeted micro-sewersheds for detection and ""true"" prevalence. Congregate facilities provideunique opportunities for study because they are controlled populations where the precise number and timing ofinfections can be defined. Our team will utilize detailed monitoring of congregate facilities to define the preciseper patient contribution and longevity of SARS-COV-2 RNA to wastewater by 1) increasing the number offacilities tested, 2) altering the frequency at which samples are collected, and 3) comparing sewershed datacollected to clinical patient case data.Although SARS-COV-2 contribution/patient varies among communities, there have been clear outliercommunities that produce little or no genetic material in the wastewater despite the presence of knownoutbreaks. The reason for this lost signal is not known, so our team will define factors that contribute to SARS-COV-2 signal suppression in wastewater by 1) defining the physical nature of the genetic material in thesewershed to better understand the types of factors that could suppress signal, 2) expanding testing withinsewersheds with suppressed signal as well as from additional facilities with similar population and industrydemographics as those with suppressed signal to narrow the sources of signal suppression, 3) performingexhaustive chemical characterization comparing wastewater from locations that are suppressed to those thatare not to identify candidate compounds that could be causing suppression, and 4) obtaining or generatingcandidate inhibitors and test their ability to suppress signal from viral genetic material in a controlledexperimental setting.",2020,2022,Missouri State Dept/ Health & Senior Srv,2000004,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen | Disease transmission dynamics | Disease surveillance & mapping",2021 +C09599,3R01MD010629-04S2,Optimization of a new adaptive intervention to increase COVID-19 testing among people at high risk in an urban community,"Project SummaryCOVID-19 has disproportionately impacted medically or socially vulnerable populations in marginalized urbancommunities across the United States (e.g., people with co-morbidities, working in high risk settings, thoserefusing or unable to adhere to the State of New Jersey (NJ) prevention guidelines). Social determinants ofhealth (SDH) such as stigma, incarceration, and poverty are associated with increased exposure to COVID-19and increased deaths. In the absence of effective, potent, and widely available vaccines and treatments,prevention - i.e., testing, social distancing, contact tracing, and quarantine -- is essential. Little is known aboutacceptability of COVID-19 testing in low-income and racial/ethnic minority neighborhoods, where residentsexperience increased barriers to prevention (e.g., inadequate housing, high-risk jobs). However, we haveknowledge of cost-effective, evidence-based, and culturally appropriate interventions that have beensuccessfully used to engage people in HIV prevention and treatment. These interventions can be adapted andtested to help address COVID-19. Navigation services (NS) increase HIV testing and adherence to treatmentwhile addressing structural barriers that deter treatment engagement in high-risk communities. Brief counselingincreases HIV treatment engagement. This study uses a Sequential, Multiple Assignment Randomized Trial(SMART) with 582 COVID-19 medically/socially vulnerable people. Guided by the COVID-19 Continuum ofPrevention, Care, and Treatment, analysis will explore factors associated with testing and adherence to publichealth recommendations. The study aims include: Aim 1: To optimize an adaptive intervention that willincrease rates of testing and adherence to NJ COVID-19 recommendations (testing, social distancing,quarantine, hospitalization, contact tracing and acceptance of COVID-19 vaccination) among high-riskpopulations. Aim 2: To identify predictors of testing completion and adherence to NJ recommendations.This study is innovative in its application of existing evidence-based interventions to address COVID-19 andthe use of SMART following Community Based Participatory Research principles. It has",2020,2022,University Of Illinois At Urbana-Champaign,1239077,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2016 +C09600,1U18TR003778-01,AFS/SERS Saliva-based SARS-CoV-2 Earliest Infection and Antibodies Detection,"Project Summary/Abstract: This U18 application is responsive to the NIH's RADx-rad Emergency Responses to the COVID-pandemic for new or non-traditional technologies developed for single extracellular vesicle, exosome andextracellular RNA (exRNA) isolation and analysis and reposition them for detection of SARS-CoV-2. Theapplicant's group is a grantee in the NIH Common Fund ""Extracellular RNA Communication (ERC)"" Programadvancing a new and emerging technology of Acoustofluidic Separation (AFS) for label-free, high yield and purityexosomes from biofluids which is coupled to extracellular RNA characterization using Surface Enhanced RamanSpectroscopy (SERS) for single EV identification. This U18 application is to reposition the AFS EV technologyand SERS for the non-invasive earliest detection of SARS-CoV-2 in saliva of infected patients. Host immunity toSARS-CoV-2 will also be assessed in the saliva samples, permitting the earliest detection of SARS-CoV-2infection and host immunity non-invasively in a saliva sample. Five Specific Aims are in place to reposition the saliva-based AFS and SERS technologies, in a 2-yearU18 proposal, to test the hypothesis that an integrated multi-parametric non-invasive saliva test for SARS-CoV-2 infection, viral load and host immunity test demonstrating clinical performance surpassing current saliva-basedSARS-CoV-2 EUA tests.",2020,2022,University of California-Los Angeles,904071,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C09601,3P30GM114737-05S1,Puipuia le Ola: Increasing reach and uptake of COVID-19 testing among Pacific Islanders in Hawaii and Guam,"AbstractNon-Native Hawaiian Pacific Islanders (PI), defined as indigenous people having origins in Guam, theCommonwealth of the Northern Mariana Islands, American Samoa, Federated States of Micronesia, Republic ofthe Marshall Islands and Republic of Palau, have among the highest COVID-19-associated morbidity andmortality rates in the U.S. PI also suffer from medical co-morbidities known to increase their risk of severeCOVID-19. In addition, PI have poor access to health care, inadequate or no health insurance, live inmulti-generational or multi-family overcrowded housing, and have low-paying service jobs that expose them tothe infected public. Hawaii is experiencing a dramatic surge in COVID-19, with triple-digit daily counts and morethan 10,000 cases. PI, who comprise only 4% of the State's population, account for 32% of COVID-19 cases.Our long-term goal is to reduce COVID-19 disparities among PI. The overall objective of the proposed researchis to use culturally resonant community-engagement strategies to increase the reach and uptake of COVID-19testing to better understand SARS-CoV-2 infection patterns among PI in Hawaii and on Guam. Our centralhypothesis is that culturally appropriate and linguistically correct strategies will increase uptake of COVID-19testing among PI, resulting in more precise SARS-CoV-2 infection and seroprevalence rates. Ourmulti-disciplinary investigative team comprises physicians and community health workers, community-engagedresearchers and basic and applied scientists. The objective will be achieved by the following specific aims.Specific Aim 1. Develop and evaluate culturally tailored community-engaged strategies to increaseCOVID-19 testing among PI in Hawaii and Guam.Approach: Engage PI communities to jointly design a strategy with culturally and linguistically appropriatecontent to promote COVID-19 testing and mplement the strategy and evaluate its effectiveness.Specific Aim 2: Determine SARS-CoV-2 infection patterns in asymptomatic PI in Hawaii and Guam.Approach: Perform COVID-19 RT-PCR and SARS-CoV-2-specific IgG and IgM testing of asymptomatic adult PIin Hawaii and Guam to ascertain infection rates and seroprevalence.A highly committed Community and Scientific Advisory Board, comprising prominent leaders in the PI communityand academicians who are dedicated to improving IP health, will provide guidance to design culturally relevantstrategies to mitigate COVID-19 disparities among PI. Strong support from the community, academia andgovernment attest to the to the urgency of this Community-Engaged Testing Research Project.",2020,2021,University Of Hawaii At Manoa,958613,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Supportive care, processes of care and management | Approaches to public health interventions | Community engagement",2020 +C09602,1R44DE030852-01,Designer DNA Nanostructure Based Biosensing for Rapid COVID19 Detection and Monitoring using Saliva Sample,"ABSTRACTA Novel Saliva-Based Aptamer Detection Assay for SARS-CoV-2 Infection(RFA-OD-20-021 STTR Application)Automated, rapid diagnostics with little sample collection and preparation are needed to identifyand trace affected persons in times when hyper-infectious pathogens cause pandemics. Frequent,low cost and highly scalable testing is the only way to gain visibility on the magnitude of thepandemic and ultimately control the spread of the disease. We propose the development of aunique system that can cheaply and readily detect SARS-CoV-2 in saliva samples. Thedevelopment of a system that uses saliva present an opportunity to readily test patients using asample that is easily collected and harbors high concentration of viral particles.The SARS-CoV-2 pandemic has predominantly affected individuals with pre-existing conditionssuch as clotting disorders, diabetes, hypertension or other chronic diseases. Patients with thesepre-existing conditions who then are infected have exacerbated symptoms and complications thatcan lead to death. For example, many patients that have succumbed to SARS-CoV-2 infectionhave developed blood clots that have impaired pulmonary or cardiac function and ultimatelycardiac failure. A rapid diagnostic using easily collected samples (e.g. saliva) would allow forinfections to be identified sooner, therapies to be administered quicker, treatment to be monitored,and ultimately leading to fewer individuals that succumb to the infection.We outline a novel DNA Star biosensing approach based on the fact that viruses, such as SARS-CoV-2, express unique spatial patterns of antigens on their surfaces, facilitating multivalentbinding to host cells for infection. These configurations of epitopes drive the high sensitivity andspecificity of our assay. Based on this naturally occurring binding mechanism, we developed arational design approach producing pattern matching designer DNA architecture for viral sensing.A proof-of-concept Dengue virus (DENV) rapid diagnostics was developed to demonstrate itspower: DENV surface antigens present the most complex geometric pattern among all knownpathogens, a DNA star linked 10-aptamers nanostructure that offers polyvalent, spatial DENV-epitope pattern matching interactions has provided high DENV-binding avidity and specificity,increasing affinity by ~1,000× compared to the conventional aptamer approach which relies onmonovalent aptamer-epitope interactions. Our POCT diagnostics detected intact DENV virions inpatient samples with PCR equivalent sensitivity in <2 mins at a cost <$0.15.Current RT-PCR molecular test are suited to large, centralized laboratories, and difficult to scalefor rapid testing of samples and delivery of results to clinicians and patients. Immunoassay testshave lower sensitivity, and patients need to develop a response to the virus in order to detect theantibody response. Our ""DNA star"" biosensor-based rapid diagnostics will provide theinfrastructure for real time SARS-CoV-2 diagnostics that is easy to use (instrument-free), faster(sample to results in minutes) and cost effective (~$3 per test).",2020,2021,Atom Bioworks Inc,1257963,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09603,1R44DE030841-01,Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array,"Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array Nucleic acid tests have become the gold-standard for diagnostic testing for COVID-19, usually performedin specialized laboratories. Most are based on reverse-transcription quantitative polymerase chain reaction(qRT-PCR). The time required for specimen transport and processing results in a turnaround time that is typi-cally several days. The few rapid (<1 hour) point-of-care (POC) tests are more expensive, still require samplepreparation and specialized reagents, and do not have the throughput needed for population surveillance. Di-rect testing for the virus, which also reduces requirements for multiple reagents, is a necessary step to improv-ing diagnostic testing. While four such antigen tests have been approved for detection of SARS-CoV-2 basedon immunoassays to the N protein, sensitivity is limited and no quantitation of viral load is possible. We will address this gap by using DiagnostikosTM, an in-development rapid POC platform for direct, real-time, multiplexed, quantitative bioelectronic detection of biomolecules that employs an all-electronic detectiondevice that functions at the single-molecule level. These single-molecule field-effect transistors (smFETs) arearrayed on a complementary metal-oxide-semiconductor (CMOS) integrated circuit chip. Chips will interfacewith an envisioned USB-stick-form-factor reader device. Robust single-domain antibodies, known as nanobod-ies and immobilized on these devices, are used for sensitive detection of viral particles and viral debris. Theuse of multiple nanobodies for a single protein and nanobodies for different proteins in a single assay allowsfor significant improvements in specificity. Nanobodies will be specific for one or more of the four major struc-tural proteins in SARS-CoV-2; the nucleocapsid (N) protein engulfing the viral RNA, the spike (S) protein, themembrane (M) protein and the envelope (E) protein. No sample preparation or specialized reagents are re-quired for detection, and the device will be designed to operate with saliva, which has very recently beenshown to be a reliable medium for detecting SARS-CoV-2. Individual sensor chips can be manufactured at acost of $35. With the addition of other nanobodies, these large dense arrays can also allow detection of manypathogens in a single test. In this Direct-To-Phase-2 SBIR program we will pursue several key innovations that are required to makesuch a platform possible, including isolation of nanobodies for key structure proteins of SARS-CoV-2 (SpecificAim 1), development of the smFET platform for antigen detection (Specific Aim 2), development of largeCMOS arrays of these smFET devices (Specific Aim 3), and verification of detection in increasingly complexsamples up to and including clinical samples (Specific Aim 4). This project is a partnership between universityresearchers who developed the smFET technology and a venture-based start-up venture, Quicksilver Biosci-ences, spun out to commercialize smFET technology and develop smFET/CMOS arrays for molecular diag-nostic applications.",2020,2022,Quicksilver Biosciences Inc,817335,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09604,3UM1AI069415-15S1,Integrated University of Puerto Rico Clinical Trials Unit,This supplemental funding application aims to increase laboratory capacity to perform COVID-19 testing in the facility at the University of Puerto Rico Medical Sciences Campus (UPR-MSC) in the general population and individuals with risk factors.,2020,2020,University of Puerto Rico Medical Sciences Campus,300000,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09618,MR/V034952/1,Tracking haulage in East Africa to support COVID-19 surveillance,"On the 13th of June, a haulage truck driver was found dead in the 32-kilometre queue of trucks at the Busia border between Uganda and Kenya. This bottleneck in regional supply chain is caused by mandatory COVID-19 testing, whose results take 14-26 hours. Waiting for test results not only represents an increased risk in COVID-19 transmission to communities but also outbreak of water borne and food borne diseases. Critically, such delays in the supply of goods and medicines for land locked countries further threaten the health and wellbeing of these populations. To mitigate this problem, the Ministry of Health of Uganda proposes to test and allow drivers continue with journeys, however, this would require a quicker approach of tracing drivers who test positive, and profile their attributable transmission risk. To address this limitation, we propose to develop and test digital contact tracing technology tailored to the haulage industry. This approach provides a unique opportunity to harness the input of users, characteristics of the haulage sector, support of government, technology firms and academia to maximise uptake and utility of such tools in a developing country context. Critically the tool will be open source, which allows for simultaneous testing of its utility in other parts of the world. In Uganda, the technology will provide the Ministry of health information on location, an alert system for cases, at-risk drivers as well as expected volume of traffic at checkpoints. This strengthens public health responses to COVID-19 and improves regional flow of supply chain",2021,2022,University of Edinburgh,360994.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09619,MR/V035444/1,Implementing genomic surveillance to support SARS-CoV-2 control and mitigation strategies in the Philippines,"As scientists and public health practitioners battle to understand and control the COVID-19 pandemic, the application of genomic surveillance i.e. tracking changes in the virus' genetic footprint, has become an invaluable tool. Genome sequences provide unique insights into how the virus is evolving and spreading and how it can be more effectively controlled. This information enhances traditional surveillance methods like contact tracing to resolve transmission scenarios e.g. providing evidence to determine the most likely route of transmission if an infected hospital worker has had multiple patient and community contacts, guiding improved infection control. It simultaneously provides a means to monitor the impact of control efforts, such as lockdown, by tracking the local extinction or re-introduction of virus lineages. We propose to build genomic surveillance and response capacity in the Philippines, where it can inform infection control at local and regional scales, e.g within healthcare settings and between different islands or provinces. We will deploy the latest sequencing and analytical technologies to characterize virus circulation from archived samples and enable rapid interpretation of genomic data from new case investigations to directly inform responses. This approach will provide crucial and transferrable insights into SARS-CoV-2 dynamics across the island archipelago and globally. Moreover, this project will build surveillance and response capacity against future viral threats and for the control and elimination of diseases that continue to pose a major burden.",2021,2022,University of Glasgow,462185.46,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Western Pacific,Western Pacific,,,,Philippines,Philippines,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2020 +C09620,MR/V036890/1,Serological tools for COVID-19 control and vaccine roll-out in Southeast Asia,"The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused immeasurable burden on economies and public health globally, including in Asia. New diagnostics for detecting the present and past exposure to the virus have been developed, and vaccines are emerging for clinical evaluation and roll-out. As the number of cases plateau, the exit strategy of Governments will involve the use of surveillance and contact tracing to limit the damage of future sporadic outbreaks in the short to medium term, while vaccination will ideally lead to elimination. However, many of the tests and vaccines under evaluation are based on the same biological targets, and infection control activities will need to distinguish immune responses to vaccines and those elicited by SARS-CoV-2 infection, which cannot yet be achieved with current front-line rapid testing kits. With this in mind, we propose to investigate alternative immunological targets arising from LSHTM modelling, informatic tools and laboratory work. These targets will be assessed within ongoing collaborations with government research institutes and hospitals in Thailand and The Philippines, who are at the forefront of clinical management and infection control in the COVID-19 response. These sites have pre-existing biological samples and data collected for diagnosis and treatment that will be used in the proposed project. We will evaluate new biological targets and establish assays that can be implemented by these countries to assist a surveillance system to monitor the progress of vaccination and SARS-CoV-2 elimination in the community. This will provide vital data for the direction of vaccine rollout and containment strategy. Most importantly, the tools developed can be easily implemented across other LMIC countries with a minimal laboratory set-up. With this, our goal, is to make a lasting contribution to Southeast Asian COVID-19 surveillance infrastructure, thereby improving the health and economy of the nations.",2021,2020,London School of Hygiene & Tropical Medicine,287447.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,South-East Asia | Western Pacific,,,,United Kingdom,Thailand | Philippines,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C09621,MR/V03698X/1,The impact of COVID-19 control measures on non-communicable diseases risk factors and metabolic health: a comparison of three Caribbean countries,"Non communicable diseases (NCDs) such as diabetes, hypertension and heart disease are the leading causes of death in Low and Middle Income Countries (LMICs). Caribbean women, urban dwellers and the poor are more likely to have NCDs and a greater burden of NCD risk factors such as obesity, physical inactivity and unhealthy diet. The recent control measures to limit the spread of COVID-19 in many LMICs interfered with daily routines and food systems. While some control measures such as limiting sale of alcohol and closure of fast food restaurants might have potential benefits on NCDs, these may be counterbalanced by limited access to fresh fruits and vegetables and a tendency to consume unhealthy stored/preserved foods. Additionally, stress, working from home, increased screen time (computer and TV) and boredom also create a change in sleep, physical activity and other NCD related lifestyle practices. In this study we will examine how control measures used in 3 Caribbean islands affected the health and lifestyle practices of people living with NCDs, particularly women, the poor and those living in urban vs rural communities. By understanding the effects of COVID-19 control measures on NCD risk factors (lifestyle practices), mental health, metabolic health (blood sugar and cholesterol) and physical measurements (blood pressure and weight), LMIC governments can use their limited resources to better care for persons with NCDs during national crises and respond better to future COVID-19 and other infectious disease outbreaks.",2021,2020,University of the West Indies,259870.56,Human Populations,Black,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Women | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Unspecified,,,,Jamaica,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09622,MR/V035592/1,"Ensuring access to health care and medicines during COVID-19: critical challenges and feasible policy options for the medicines retail sector, East Africa","Managing pandemics and ensuring ongoing access to medicines is a difficult task for any government. In most high income settings, this can be achieved by activities focussed on public health systems. In countries such as Uganda, however, 40-70% of medicines for fever, headaches and cough are delivered through drug shops, private clinics and pharmacies. Governments need to create policies and programmes so that the medicines retail sector (MRS) can continue to provide treatment for common infectious diseases like malaria and bacterial pneumonia; does not become a 'hotspot' for disease transmission; and can actively contribute to the public health response during disease outbreaks. It is difficult for governments to know how to involve the MRS in responses to COVID-19. There are few guidelines to draw upon. The World Health Organisation is seeking ways to better support private sector actors so that they can be an effective part of the COVID-19 response and continue to provide care for other illnesses. Their work is stymied by a lack of evidence. This project is part of a long standing collaboration between researchers in Uganda, UK and Denmark. It will build on recent research in the retail sector to rapidly create and disseminate new evidence on: the impact of current policies (including lockdown and curfew) on the MRS and community access to treatment; the ways in which members of the MRS are willing to be involved in COVID-19 public health response (health education, testing, surveillance); and what this would cost to scale up in the country.",2021,2020,London School of Hygiene & Tropical Medicine,257750.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Europe,,,,United Kingdom,Uganda | United Kingdom | Denmark,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Indirect health impacts | Health service delivery,2020 +C09623,MR/V036157/1,CARE: COVID-19 and antimicrobial resistance in East Africa - impact and response,"There is a growing worry that knock-on effects originating from the response to COVID-19 will cause greater threats to human health in the future. One such area is antimicrobial resistance (AMR) caused by the overuse of antibiotics (AB). Responding to COVID-19, governments have imposed restrictions on everyday life to stop the virus spreading. Whilst these may be successful in combating the virus, they are changing the way people seek medical help for infections, and the way in which people use ABs when they feel ill. In order to help make sure that ABs retain their effectiveness, we need to understand more about how COVID-19 is directly and indirectly impacting on AB use and availability in communities. To do this we are going to build on existing studies in Tanzania and Uganda. We will enrol patients who have symptoms of common diseases caused by bacteria, and find out about how they seek treatment and get and use ABs. In their communities, we will find out about the availability of ABs by interviewing doctors and sellers of ABs, and more widely, we will find out how community members have received and responded to health messages on COVID-19. Using this information we are able to assess change in the situation by comparing with our pre-COVID-19 research information from the same locations. This will help identify where behaviours have changed and whether antibiotics are been used unnecessarily, so that steps and measures can be identified and introduced that can help communities use antibiotics more effectively, and therefore reduce the risk of increasing AMR.",2021,2022,University of St Andrews,681234.24,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Unspecified,Hospital personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Tanzania | Uganda,"Policies for public health, disease control & community resilience",Community engagement,2020 +C09624,MR/V036912/1,Indigenous peoples responding to COVID-19 in Brazil: social arrangements in a Global Health emergency,"This proposal is focused on indigenous peoples' response to the COVID-19 pandemic in Brazil, a country which now has the second highest number of infected people in the world (2,962,442 cases by 7th August). Indigenous peoples are taking responsibility to contain the spread of the new virus among their communities into their own hands. Using anthropological knowledge and methodology, we will identify indigenous responses and help to mobilise strategies to mitigate risk. We will work closely with the special agency for indigenous health (SESAI), and we aim to cooperate with global and public health agencies and policies, as well to engage decision makers to shape better responses to face this outbreak. Three programme themes will frame the research and actions: 1. Health, Care and Death; 2. Mobility and Circulation; and 3. Gender. A digital platform 'Amerindian Response COVID-19 - Anthropology Platform' will also be developed and used as a tool to publish brief reports in real time, using different media, including podcasts and video diaries, in addition to academic papers. Monthly reports will be addressed to SESAI and eight case studies will be conducted across Brazil's regions. The project will have an important impact to mitigate the severe impact of this pandemic on indigenous people. It will also provide vital lessons to increase resilience for the future for Brazil, for all nations with large indigenous communities and for other nations where community-based responses may be a key to help prevent transmission and loss of life.",2021,2021,City University of London,287670.66,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas,,,,United Kingdom,Brazil,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Community engagement | Policy research and interventions | Systemic/environmental components of capacity strengthening,2020 +C09625,20/005,The Impact of the COVID-19 Pandemic on Tuberculosis Service Delivery in Nepal,"There are 10 million cases and 1.5 million deaths from TB annually. The COVID-19 pandemic has interrupted TB diagnosis and treatment in high TB-burden settings. This increases the risk of drug-resistant TB and threatens TB control. To improve TB service resilience to crises, we need to understand the impact of different factors on service delivery, including lockdown restrictions, healthcare worker illness, resources diversion and logistic interruption, including of personal protective equipment. We will conduct interviews with TB care-providers and patients and gather evidence to quantify the COVID-19 impact on TB services to develop recommendations for service delivery in future emergencies.",2021,2021,"Birat Nepal Medical Trust (BNMT), Kathmandu, Nepal",6651.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,South-East Asia,South-East Asia,,,,Nepal,Nepal,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09626,20/090,"Effect of COVID-19 total lock down on severity of non-communicable diseases in HIV positive patients in Kampala, Uganda","On 21ST March 2020, Uganda reported the first case of COVID-19 and by 1ST April 2020, a total lock down was instituted by the government to limit the spread of COVID-19. Despite the continuity of health services, patients living with both acute and chronic illnesses are not able to access health services. We propose to conduct a cross-sectional study using a mixed methods approach to determine the effect of COVID-19 total lock down on severity of non-communicable diseases among HIV patients obtaining care from Kasangati health Center IV.",2021,2021,WHO,6700,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,International,Africa,,,,International,Uganda,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09627,20/001,Understanding Covid-19 survivor experiences and Community attitude in Uganda: Lessons for Community reintegration,"1) Project background, context and needs addressed As Covid-19 continues to ravage the world since its declaration as a pandemic, the average global fatality rate stands at 3.4%, and this is higher among adults aged 70 years and above ranging from 8% to 42.4%2. Despite this, the number of people recovering from the disease has increased over time. The mainstay approaches to management of Covid-19 are case identification, isolation and supportive care till recovery. It is also required that contacts of individuals who test positive for Coronavirus are quarantined for a minimum of 14 days. These long durations of isolation might increase anxiety and stress levels of individuals. Long durations in isolation are also likely to have a negative impact on the individuals' work, with many of the affected individuals likely to lose jobs in the aftermath of the infection because of long periods away from work and discrimination from employers and fellow employees. This, coupled with reports of disease reactivation in some individuals who have previously recovered from Covid-19 and associated disease severity and high mortality rates among adults and the way Covid-19 is portrayed by country leaderships stimulate more panic and fear in the general population. Fear during a disease outbreak can lead to stigma towards infected individuals, their families and communities even after recovery as noted during the Ebola outbreak in West Africa. The resulting stigma might persist for over two years following recovery affecting the individual socially, psychologically and economically for example physical or verbal assault, labelling and stereotyping in society, discrimination and loss of societal status previously held in community affecting the reintegration of recovered individuals into the community. There is currently little information on the impact of fear on community reintegration of patients following recovery from Covid-19 worldwide, and in Uganda in particular. However, there are cited cases of recovered patients in Uganda not wanting to be identified due to the fear of stigma in the community. There have also been cases of individuals who have completed quarantine being physically assaulted by locals accusing them of putting the community at risk of Coronavirus infection. It is predicted that due to such attitudes, many individuals in Uganda will lose the sources of livelihoods. It is also predicted that individuals may develop serious psychological conditions and if not identified and properly managed, victims are likely to suffer long-term mental and emotional issues including depression, suicidal tendencies, self-stigmatisation, anger, anxiety, worthlessness, substance addiction, grief, guilt among others. It is important, therefore, to understand community reintegration following recovery from Covid-19 from the policymakers, patients and community perspectives. This information will be used to better inform the design of community reintegration interventions that are specific to Covid-19 pandemic. 2) Aims or research questions being addressed With this study, we aim to; 1. Understand the community reintegration strategies that the Uganda government is employing for recovered Covid-19 patients 2. Understand the experiences community reintegration of Covid-19 survivors 3. Understand knowledge, attitudes and practices of the wider community towards Covid-19 survivors 4. Design and recommend an evidence-informed strategy for reintegration of Covid-19 survivors in the Uganda context 3) Study design This will be a cross-sectional study, utilising key informant interviews, in-depth interviews and an online survey to collect qualitative data. Study setting: The study will be carried out in Uganda. We will target communities that have had a case of Covid-19 and those without a case. This is aimed at comparing the knowledge and attitude of the two communities. Study Population: We will collect data from policymakers, individuals who have recovered from Covid-19, community leaders and the general public. Policymakers: We shall interview officials at the Ministry of health who are directly responsible for the community reintegration of covid-19 survivors. In responding to Covid-19 pandemic in Uganda, the Ministry of Health set up different teams to address different aspects of the pandemic. We shall identify the team or members directly responsible for reintegration. Covid-19 survivors: Uganda has had 75 cases of Covid-19 to date and over 40 individuals recovered and back to their communities. We shall sample from the recovered individuals for the interviews. Community/opinion leaders: These will be identified by the local leadership of communities where Covid-19 survivors hail from. These shall be identified by the local council one chairpersons and shall be approached for participation in the study. They will be selected conveniently based on whose contact we can get. Due to social distancing requirements and country-wide lockdown, we intend to collect data from the above participants via targeted phone calls for interviews. With some policymakers who prefer responding in writing, we shall email the interview questions and follow up with a phone to call to confirm receipt of the email. The responses shall be recorded and transcribed for analysis. General population: We shall conduct an online survey which seeks to identify the attitude of the community towards Covid-19 survivors. We shall use SurveyMonkey, an online survey platform. The survey shall be widely promoted to ensure that persons from different parts of Uganda respond to the questions. Analysis plan: We will use Dedoose software for the analysis of the data. Two independent individuals will code the same data sets, and we will use the codes to develop themes in the analysis using the framework analysis approach. Ethical Approval: We shall obtain ethical approval for the study from the School of Medicine Research and Ethics Committee (SOMREC) and the Uganda National Council of Science and Technology. We will also obtain written consent from all participants in the study. The data collected during the study will be anonymised and only accessible to the study team. 4) Approach used to maximise the impact of research outputs, to improve health and the research community The information from the study will be used to identify gaps and strengths in the community reintegration approach used by Uganda. We shall use these gaps to draw recommendations on how to improve the reintegration process and address the community fears and potential stigma towards Covid-19 recovered patients. The results will be shared in form of a report with decision-makers at the Ministry of Health with whom we have worked on different policy projects and the National Task Force for Covid-19. We shall also produce a two-page document that we shall share along with the report being cognisant of some policymakers not creating time to read the full report. These shall also be uploaded online so as to make them accessible to a wider audience. We shall also publish a paper in an open-access peer-reviewed journal to provide lessons for the world at large on the different things they need to consider during reintegration of recovered patients. Expected outcomes We expect that the study findings will be used by the policymakers to further refine the integration process. With a better reintegration strategy, it is expected that the patients will face less stigma in the community and thus reduced to no adverse effects on their social, psychological and economic aspects of life. My role in the project I will be the technical lead on this project. I will lead the protocol development process, data collection, analysis, report preparation and results dissemination.",2021,2021,Makerere University,6407.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts,2020 +C09628,20/032,Evaluation of Covid-19 country-wide testing capacity in Uganda,"Evaluation of Covid-19 country-wide testing capacity in Uganda Project background, context and needs addressed Covid-19 Disease is arguably the most prominent pandemic of our time, having grown from a small outbreak in Wuhan province China to a global pandemic within just 3 months. This rapidly growing disease has left many dead, and even big economies pressed down on their knees and overwhelmed by cases. Whereas Africa has remained least affected, the World Health Organization (WHO) has consistently warned of dire consequences if community transmissions start in Africa where the health care systems are already weak(1). Indeed, community transmissions and sporadic cases have been reported in Africa, with more than 23,000 cases reported in 52 (96%) countries(2). In this regard, Uganda is not spared. As I write, there are 56 confirmed cases with over 5000 being monitored for Covid-19 symptoms(3). In response to the pandemic, countries have been plunged into lock-down with associated social and economic effects, people are advised to observe social distancing, there are restrictions on movement and also an emphasis on testing(4). Whereas these measures have been effective in countries such as China, the one shoe fits all approach may not work in Uganda and many other Low and Middle-Income countries where most people live from hand to mouth and live in crowded conditions. Accordingly, there is a need to reinforce these measures with a strategy of rapid and early detection for those with Covid-19, contact tracing and quarantine to limit exposure to the community. Indeed, this approach worked well for South Korea, a country where by early February 2020 had rapid community transmissions and used early testing and contact tracing as an approach to successfully limit the spread of the virus. When the first case was first detected in South Korea, the country made deliberate efforts to set up testing centers that were free of charge, increasing the capacity of the country to run over 20,000 tests a day(5). This ensured that 90% of the suspected cases and their contacts are tested and monitored to limit exposure to the community(6). Because of this approach, the country has successfully brought down the infection rates from 700 people per day to less than 10 people(7) as we write. Drawing from this success, countries are redesigning their strategy to adopt the South Korean approach to ensure testing facilities are available and accessible. More so, estimates suggest that about 80% of people with COVID-19 have a mild or asymptomatic disease, therefore, relying on symptomatic management will leave out asymptomatic individuals who are likely to spread the infection within the community(8). This provides a strong case for wide-spread testing of Covid-19. In Uganda, the government anticipates the national central testing facility to be overwhelmed by the ever-growing number of suspected cases together with their contacts and is moving to roll out the testing to regional centers, particularly regional referrals hospital laboratories and private laboratories. It should be noted that Covid-19 nucleic acid amplification tests require at least biosafety level 2 laboratories(9). Moreover, the currently available tests are molecular tests that include RNA manipulation and therefore full precautions associated with molecular assays. Whereas the move is set to greatly increase the accessibility to the test and eventually lower the turn-around time, the majority of the centers have never conducted molecular tests before and therefore their capacity in terms of human resources, and infrastructure remains questionable. It is basing upon this background that we propose to evaluate the Covid-19 testing capacity in the country. Aims or research questions being addressed To evaluate the country-wide diagnostic capacity of Covid-19 in Uganda Study Design This will be a descriptive cross-sectional study to evaluate the Covid-19 diagnostic testing of Uganda. Approach used to maximise the impact of research outputs, to improve health and the research community Sampling method Purposive sampling will be employed to select all the 16 Regional referrals hospital laboratories, 2 National reference laboratories and 5 private laboratories which have been earmarked as potential testing sites. Assessment tool An adapted version of the WHO Laboratory assessment tool (LAT) will be used for data collection. The WHO LAT is a generic tool that contains several modules (each assessing a laboratory core capacity) and indicators that can be adapted to evaluate specific core laboratory capacities(10). For this evaluation, we shall select 10 modules from the WHO LAT as follows; i)Documents, ii)Sample collection, processing and handling, iii) data and information management, iv) consumables and reagents, v) equipment, vi) laboratory testing performance, vii) facilities, viii) human resources, ix) biorisk management and x) public health functions of the lab). Each of the 10 modules has multiple indicators (ranging from 2-10 per module), which will be scored out of 100%. The module score will be calculated as an average of the indicator scores. The laboratory assessment score will be an overall average of the 10 module scores. The modules will be adapted to the Ugandan setting with slight modification of words to improve comprehension. Data collection and analysis Ethical approval will be sought from the Lira University Institutional Review Board (IRB) and thereafter the study will be registered with the Uganda National Council for Science and Technology. Research assistants will be trained on the use of data collection tools and then dispatched to collect data in a team of 2. A researcher administered questionnaire will be used to collect data from laboratory managers and an observation checklist will be used to collect data during laboratory inspection. The survey data will be double entered into an excel database and reconciled to identify inconsistencies and missing data. Data Dissemination plan Data dissemination is an essential part of our project and we propose to share research findings with policymakers and the wider scientific community. For policymakers, we shall avail and discuss a copy of the research report to the scientific committee of the Covid-19 task force in Uganda. For the scientific community, we shall publish the findings in a peer-reviewed journal, present at scientific conferences and make a copy available at the Lira University website. Expected outcome and significance To determine the Laboratory capacity, module scores will be rated as follows; strong (≥85%), good (70-84%), Weak (50-69%) and very weak (<50%). This will ultimately inform on the country-wide testing capacity of Covid-19 which is a central factor in pandemic control. Additionally, this data will identify core laboratory areas of strength which Uganda and other Low and Middle income Countries (LMICs) countries can benchmark to be better prepared for future epidemics. We shall also identify areas of weakness where technical persons, policy makers and partners can jointly address. Role in the project As a principal investigator, I will be responsible for the direct oversight and coordinating daily operations. This includes ensuring all the regulatory processes including ethical approval, registration, and administrative clearance is obtained, ensuring the study team is trained and that data collection and analysis are conducted to the required standards. I will lead the study team to share findings with all the relevant stakeholders including laboratory heads, policy makers, technical persons and the wider scientific community. References 1. Swalani S. COVID-19: Africa told to prepare for worst. What's the response? Al Jazeera2020 [cited 2020 7th April]. Available from: https://www.aljazeera.com/news/2020/03/covid-19-africa-told-prepare-worst-response-200319085112877.html. 2. African_Agurments. Coronavirus in Africa Tracker: African Arguments; 2020 [cited 2020 8th April]. Available from: https://africanarguments.org/2020/04/07/coronavirus-in-africa-tracker-how-many-cases-and-where-latest/. 3. MOH. Coronavirus (Pandemic) Covid-19 Kampala, Uganda: Ministry of Health Uganda; 2020 [cited 2020 8th April]. Available from: https://www.health.go.ug/covid/. 4. WHO. Basic protective measures against the new coronavirus: World Health Organization; 2020 [cited 2020 April 8th]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. 5. Fleming S. South Korea's Foreign Minister explains how the country contained COVID-19: World Economic Forum; 2020 [cited 2020 April 8th,]. Available from: https://www.weforum.org/agenda/2020/03/south-korea-covid-19-containment-testing/. 6. Levkowitz A. South Korea's Approach to Coronavirus 2020 [cited 2020 April 8th]. Available from: https://besacenter.org/perspectives-papers/south-korea-coronavirus/ 7. South Korea's new coronavirus cases fall to single digits: Al Jazeera; 2020 [cited 2020 April 21st ]. Available from: https://www.aljazeera.com/news/2020/04/south-korea-coronavirus-cases-fall-single-digits-200419031505830.html. 8. Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TD. How will country-based mitigation measures influence the course of the COVID-19 epidemic? The Lancet. 2020;395(10228):931-4. 9. WHO. Laboratory biosafety guidance related to coronavirus disease (COVID-19) Geneva: World Health Organization; 2020 [cited 2020 April 7th ]. 10. WHO. Laboratory Assessment Tool. Annex 2: Laboratory Assessment Tool / Facility Questionnaire: World Health Organization; 2012 [cited 2020 April 8th ]. Available from: http://www.who.int/ihr/publications/Annex2_en.xls?ua=1.",2021,2021,Lira University,6250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09629,20/035,Perceptions and Behaviors related to Hand Hygiene for the Prevention of COVID 19 transmission among community members in Eastern Uganda during a pandemic period,"Perceptions and Behaviors related to Hand Hygiene for the Prevention of COVID 19 transmission among community members in Eastern Uganda during a pandemic period Project Background, context and needs to be addressed The Corona Virus Disease 2019 (COVID-19) first discovered in Wuhan, China and declared a pandemic by the World Health Organization on 11th March 2020 is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (Guo et al., 2020). As of 18th April 2020, COVID-19 had infected over 2 million people and caused an estimated 140,000 deaths in 210 countries worldwide (Johns Hopkins University, 2020). Uganda as of 18th April 2020 has 55 confirmed cases with 35 active cases, 20 recoveries and no deaths (Ministry of Health Uganda, 2020). Across the globe, several measures have been enacted by governments in order to slow the spread of the virus; some of the measures are social distancing, hand washing with soap and water or use of an alcohol-based hand sanitizer. As no vaccine for COVID 19 had has been developed, the Ugandan government has attempted to mitigate the spread of disease by reducing transmission. Infected individuals are being identified, isolated and treated while public health campaigns have been initiated to educate the general public about preventive behaviours that reduce the risk of transmission. The specific techniques recommended include sneezing into a tissue and washing hands regularly with soap and water. Given that the evidence regarding the preventive effectiveness of wearing a facemask is inconclusive, hand hygiene is considered the easiest and most effective measure to prevent the spread of COVID 19. Previously, multiple studies were undertaken to identify the factors that most effectively motivated people to adopt specific hand washing behaviours. Amidst all the stated interventions, the community members still have a challenge with adhering to hand washing habits. In some places there are not hand washing facilities or some are non-functional. The current study aims to assess the perceptions, attitudes and motivating factors regarding hand washing during the peak period of the COVID 19 pandemic through the use of a cross sectional survey model. Aims or research questions being addressed To assess the perceptions, attitudes and motivating factors regarding hand washing during the COVID 19 pandemic. Study design A cross sectional survey with both quantitative and qualitative methods will be used. The study area will be carried out Mbale district in eastern region of Uganda. Sample size will be calculated using the Kish Leslie formula. A questionnaire will be developed and administered to community members by trained research assistants. Study participants will include adults who consent to participate in the study. In addition, four to six focused groups will be conducted to explore the perceptions and motivating factors. Ethical approval will be sought from Mbale Regional Referral Hospital Research and Ethics Committee. Approach used to maximise the impact of research outputs, to improve health and the research community This will be a community study and will employ both quantitative and qualitative methods. Expected outcomes This study will bring out information regarding perceptions and attitudes towards hand washing. The current hand washing habits and motivating factors will be documented. This information will inform the Ministry of Health about the success of the ongoing public education campaigns regarding hand washing. The information will also guide planning for future campaigns on hand hygiene during a disease outbreak. Your role in the project I'm the principal investigator in the project. I conceived and designed the concept. I hope to work with a team of colleagues to carry out the study. I will be responsible for the leadership, accountability, monitoring and evaluation of the project. I will fully engage in the process of data collection. I will also take lead in the data analysis and report writing process. References Guo, Y.-R., Cao, Q.-D., Hong, Z.-S., Tan, Y.-Y., Chen, S.-D., Jin, H.-J., ... Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-an update on the status. Military Medical Research, 7(1), 1-10. Johns Hopkins University. (2020). Coronavirus Resource Center. Ministry of Health Uganda. (2020). COVID-19 Status Report. Kampala, Uganda. National Drugs Authority. (2020). Guidelines on hand sanitizers for use in COVID-19 Pandemic. World Health Organization. (2015). Guide To Local Production: Who-Recommended Handrub Formulations, (April), 1-9.",2021,2021,Busitema University,6432,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09630,20/037,"""Ethical dilemmas in times of COVID 19: Screening and tracing methods in the Zambian context""","Please detail your project under the following headings 1) Project background, context and needs addressed Early this year, a novel zoonotic infection by the coronavirus (SARS-CoV-2) began causing COVID-19 across continents, leading the World Health Organization (WHO) to declare it a pandemic on 11th March 2020(1). This third zoonotic coronavirus, after SARS-CoV and MERS-CoV, is widely believed to have emanated from bats and the source is linked to the seafood market in Wuhan, China with a few studies suggesting otherwise (2). While ""infection is normally characterized by respiratory symptoms, which indicates droplet transmission,"" some patients present with gastrointestinal symptoms and/or shed viral RNA or live infectious virus in faeces suggestive of faecal-oral transmission (3). Worryingly, some patients presented with symptoms after exposure to pre-symptomatic COVID19 cases. Given the implications of human interactions for the spread of infectious diseases, preventive measures include early case detection and quarantine even if asymptomatic (4). Since its first confirmed COVID19 cases in mid-March, Zambia has recorded a total of 88 confirmed cases (as at 26th April, 2020), with a surge in the number of cases after the death of a patient posthumously diagnosed with COVID-19 (5). Based on the public health Act, the government is mandated to impose measures to enhance health security and further statutory instruments have been invoked to empower officials to ""intrude"" the privacy of citizens and limit social interactions(6). With evidence that even one case can lead to a significant increase in the number of infected persons, the government has embarked on phone surveillance on persons who may have travelled or been in contact with a Covid19 patient. People have been requested to call a toll-free number to report not just themselves but also other persons suspected to be exposed to, or having signs of, COVID-19. We propose to study the ""limitation"" of individual rights and choices in times of pandemics through the lens provided by the theories of harm and rational egoism. The principle of harm contends that the actions of individuals should only be limited to prevent harm to other individuals (7). While the theory of rational egoism centres upon the idea that the rational thing to do must be to pursue one's own self-interest or that each person has but one ultimate aim, their own welfare (8, 9). These theories are used in understanding actions towards individuals and choices that individuals are likely to make and for whose benefit. For example, Everett et al reported that, despite strong heterogeneity in response, perceived benefit to others rather than 1) for the self or 2) for the innate virtue of recommended behaviours, motivated their U.S.-based sample to consider taking up preventive practices. This finding led to their suggestion that public messaging that emphasizes duty and responsibility to significant others. Thus, such information is useful to inform public health interventions and motivate desirable behaviours during emergency and pandemic situations. 2) Aims or research questions being addressed Aim: To identify the ethical dilemmas in times of COVID 19 concerning the screening and tracing methods in the Zambian context This research raises two primary ethical questions 1. What is the greater good in this pandemic? 2. What are the ethics of collecting information from patients? More specifically: a. What are the consequences of sharing the names of those with COVID-19 so that people who were in contact with them in the previous 7 days can seek testing services? b. What the implications of people refusing to give information regarding the people they have been in contact with forced to give this information against their will? c. What if persons with COVID-19 and/or their contacts knowingly give you inaccurate or incomplete information, for example, to conceal their whereabouts from significant others? d. What if they unknowingly provide inaccurate or incomplete information, for example, due to recall bias? e. What lessons can be learnt from the Zambian experience during the COVID19 pandemic? 3) Study design We propose a qualitative exploratory study. The philosophical principle of harm and theory of rational egoism and the ethical Delphi method will be used as basis for the inquiry. The ethical Delphi method is a method of inquiry, usually used in mixed methods, but in this case will be used qualitatively to get iterative participatory exchange of views and arguments on ethical issues by experts on the topic. An open-ended questionnaire will be sent to 20 different experts individually and their views will be used as basis for further study activities. 10 bio-scientists and frontline personnel in the fight against Covid19 will be interviewed and 8 ethicists will be invited to 5 Focus Group Discussions (FGDs) using zoom video conferencing. The recordings will be kept on a password protected computer and only be available to the research team. 10 Patients and those interviewed for contact tracing after travel or close intraction with a known case will also be interviewed by phone to get their perspective. The data will be analyzed using thematic analysis, where common themes will be drawn from the data and explained. A total of 20 In-depth interviews (IDIs) and 5FGDs will be conducted virtually. The participants will be purposively sampled for their expertise in research ethics and their experience in dealing with the COVID 19 cases and the whole process of screening for cases and planning to combat the pandemic. 4) Approach used to maximise the impact of research outputs, to improve health, and to the research community In order to maximize the impact of our research outputs, we will publish research findings in an open access journal for a wider coverage. This will help disseminate findings and lessons learnt from the Zambian perspective that may apply in similar settings for better health outcomes and community health. Recommendations will be drawn and shared with the Ministry of Health (MOH) through Zambia National Public Health Institute (ZNPHI) to improve emergency epidemic and pandemic case management with regard to ethics. 5) Expected outcomes 1. The project is expected to provide exploratory findings that may produce new comprehension or lead to other form of research inquiry 2. Ethical dilemmas in times of pandemics like COVID19 and some possible ways to deal with them will be identified 3. Detailed scrutiny of ethical implications of the Zambian Public Health Act and the relevant statutory instruments invoked to facilitate health security. 6) Your role in the project I will be the Principle Investigator in the project. My role will include overseeing all research activities including but not limited to collecting and analyzing the data, and dissemination of the findings. It will be my role to ensure the smooth and timely running of the whole project from inception and ensuring that the funds are being used as per budget. 1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta bio-medica : Atenei Parmensis. 2020;91(1):157-60. 2. Mackenzie JS, Smith DW. COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don't. Microbiology Australia. 2020:Ma20013. 3. Hindson J. COVID-19: faecal-oral transmission? Nature reviews Gastroenterology & hepatology. 2020. 4. Read JM, Eames KT, Edmunds WJ. Dynamic social networks and the implications for the spread of infectious disease. Journal of the Royal Society, Interface. 2008;5(26):1001-7. 5. Institute ZNPH. COVID19 updates. 2020. 6. Ministry of Legal Affairs GotRoZ. The Public Health Act: Chapter 295 of the lwas of Zambia. 2013. 7. Turner PN. ""Harm"" and Mill's Harm Principle. Ethics. 2014;124(2):299-326. 8. Cholbi M. The Moral Conversion of Rational Egoists. Social Theory and Practice. 2011;37(4):533-56. 9. Shaver R. Rational Egoism: A Selective and Critical History. Cambridge University Press 2009.",2021,2021,The Centre for Infectious Disease Research in Zambia (CIDRZ),6450,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Zambia,Zambia,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Research | Research to inform ethical issues related to Public Health Measures | Community engagement,2020 +C09631,20/038,The impact of household structure on the effectiveness of shielding vulnerable populations against COVID-19 transmission: an agent-based modelling study,"PROJECT BACKGROUND COVID-19 is an emerging infectious disease of global importance. As a rapidly progressing public health crisis, responsive interventions must be appropriate to the context and evolution of the epidemic. Many countries around the world have adopted widespread measures aimed at the whole population, such as national lockdowns, travel bans and extreme social distancing regulations. However, due to the high social and economic costs, these measures are not sustainable indefinitely. As these measures are relaxed or as the epidemic progresses, targeted interventions that protect the most vulnerable populations (such as the elderly and those with co-morbidities) will be required to minimise the number of severe cases and death. One of the core public health objectives of the European CDC is to ""Reduce morbidity, severe disease and mortality in the population through proportionate non-medical countermeasures, with emphasis on protecting vulnerable (high-risk) groups, until effective vaccines, treatments and medicines become available."" Several countries have already adopted a strategy of ""shielding"", which is a measure to protect extremely vulnerable people from coming into contact with coronavirus, by minimising all interaction between them and others. The definition of who should be shielded and how stringent the shielding advice is varies by setting. The majority of countries implementing targeted shielding techniques are high-income with household structures that facilitate shielding. However, it is unclear how effective this would be in settings with highly mixed populations, substantial differences between urban and rural settings, large proportions of the population living in informal settlements, and multi-generational household structures. South Africa is an example of a country with these dynamics, as well as having one of the highest GINI coefficients in the world, reflecting a deeply inequal society. While we can learn lessons from the early stages of shielding in high-income settings, understanding how these factors might influence the effectiveness of potential interventions such is critical to creating an effective, context-specific COVID-19 strategy. Mathematical modelling of infectious diseases provides a tool for policy makers and public health planners to predict the impact and cost-effectiveness of possible intervention strategies. This facilitates the effective planning and implementation of interventions, and the appropriate allocation of resources for maximum benefit. Our project will use agent-based modelling to estimate the impact of household structure on the effectiveness of shielding in South Africa. This can help inform evidence-based, context-appropriate interventions for reducing COVID-19-related hospitalisation and mortality in low- and middle-income countries. RESEARCH OBJECTIVES 1. Develop an agent-based model of COVID-19 transmission in South Africa 2. Project the number of COVID-19 cases, hospital and ICU admissions, and deaths averted under different shielding strategies (using several age and co-morbidity cut-offs) and household structures. STUDY DESIGN Study overview and setting We will develop an agent-based probabilistic simulation model coded in Python and visualised in Gephi. Compared with compartmental or population-based modelling, using an agent-based model allows significant flexibility in modelling micro-level process and individual-level behaviour. The model uses the population and age structure of South Africa. It will capture the dynamics of representative populations from different settings in South Africa incorporating the household structures and social mixing patterns (age and location based) in urban versus rural settings, and formal versus informal settlements. The model follows this population over time at an individual level through different stages of the disease. Model methodology A time varying agent-based model applying network theory will be used to capture contacts between individuals within a synthetic population. In the model, each agent is assigned to a household and an occupation, which is either work, school or ""other"". The agents follow a timetable assigning to them a location (household, occupation or other) for each timestep, with a parameter allowing for per-agent deviation from this timetable. On a given timestep, each place randomly assigns contacts between agents currently at this place. The probability distribution on possible contact assignments accounts for parameters such as the expected number of contacts per agent and the increased likelihood of a given agent more frequently contacting certain other agents. The agents are assigned an age, which is drawn from the South African age distribution. The disease dynamics are incorporated per agent such that each agent has a specified disease state and contacts between infectious and susceptible individuals may result in the susceptible individual moving to the exposed state. The model will be verified in several ways. One verification uses two studies of contacts in a South African population which break up the location of these contacts by place (home, school, work or other). This gives a constraint on the distribution on per-agent contacts per day per place. Another verification check uses South African Household Census data to confirm the allocation of people to households with a particular focus on household structure. An SEIR compartmental model which has already been used to assist the South African National Department of Health will be used to verify the disease dynamics component of the model. Study data The model will be informed by published and pre-print academic literature, global COVID-19 case information (specifically from the European CDC, World Health Organization and China CDC), South African population statistics from Stats SA's 2019 mid-year report, national and provincial case and testing details from the South African National Institute for Communicable Diseases and https://sacoronavirus.co.za/category/press-releases-and-notices/. As a new disease, there is much yet to be understood epidemiologically about how COVID-19 manifests and how it spreads. We will therefore conduct sensitivity analyses on key model parameters, including probability of transmission upon contact with an infectious individual and the asymptomatic proportion of infections. EXPECTED OUTCOMES & RESEARCH IMPACT The study will estimate COVID-19 cases (by age and severity), hospitalisation and ICU admissions, and mortality rates under different intervention scenarios, settings, and household structures. Results from this study will be disseminated in two ways: 1. As a publication in a peer-reviewed journal. 2. As a policy-focused report for the South African COVID-19 Modelling Consortium. Although the model is tailored to a South African context, the results can be applied to similar settings. As there is limited research on appropriate, long-term COVID-19 strategies in low- and middle-income countries, we anticipate this study will contribute to a better understanding of effective, context-specific intervention options in these settings. Where data sharing agreements allow, the model code can be made accessible to the research community. This extends the scope of research impact as it enables researchers from other countries to tailor the model to their own setting. MASHA is a member of the South African COVID-19 Modelling Consortium, a group of individuals and institutions with expertise in a range of scientific disciplines that has been convened to provide modelling support to decision makers tackling the COVID-19 epidemic in South Africa. This provides an ideal forum for presenting the study's policy-focused report and engaging decision-makers around the research results. PROJECT TEAM & ROLES Applicant/Primary researcher Rachel will be involved in all phases of the project: model development, intervention simulations, manuscript and policy brief writing. Co-researcher Jared Norman (Researcher at MASHA): Jared is a computer scientist with a background in pure and applied mathematics. His research interests are in agent-based modelling and simulation, GPU computing, and mathematical modelling of infectious diseases. He has experience in the development of user-friendly computer applications designed to allow policy makers to run simple mathematical models and navigate the output of complex models with the aid of interactive graphs. Jared's role in this project will be to provide technical support on the development of the agent-based model and simulations. Supervisor Dr Sheetal Silal (Director of MASHA): Sheetal is a mathematical modeller and statistician focusing on infectious diseases in South Africa, sub-Saharan Africa and the Asia Pacific region. Her interests are in epidemiological and economic modelling to support intervention planning and policy development. Sheetal is the founder and Director of MASHA, a senior lecturer at the University of Cape Town and an Honorary Visiting Research Fellow in Tropical Disease Modelling at the University of Oxford. Sheetal will supervise the project and be the primary contact for the policy brief submission to the South African COVID-19 Modelling Consortium.",2021,2021,University of Cape Town,6398.4,Other,Not applicable,Not Applicable,Rural Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,Epidemiological studies,Disease transmission dynamics,2020 +C09632,20/044,Barriers faced by urban homeless women in accessing Maternal and Child Health Services in the wake of COVID-19 in Delhi,"1) Project Background, context and needs addressed The provision of maternal healthcare in India is grossly inadequate, characterized by high levels of maternal mortality and morbidity and underutilisation of services, especially among the poor. While the maternal mortality ratio has reduced in India (Office of the Registrar General, India, 2018), the country is far behind the goal of achieving SDG target of 70 deaths per 1,00,000 live births (Suri, 2019). Studies indicate low levels of utilization of maternal health care among the urban poor (Agarwal et al., 2007; Siddaiah et al., 2018) as well as poor health outcomes such as prevalence of anaemia (Diamond-Smith et al., 2016; Dwarkanath et al., 2018). An ongoing ethnography carried out by researchers at the George Institute for Global Health (January 2019-June 2020) in Delhi, India, identified barriers to utilization of Maternal and Child Healthcare (MCH) services among homeless women. This is shaped by the unique vulnerabilities faced by the homeless as well as the lack of outreach of the health system. With the outbreak of coronavirus disease (COVID-19) in India, we have begun to observe that the homeless are unable to practise ideas of physical distancing, handwashing and other aspects of infection control, which places them at disproportionate risk of infection. Worse, with an already overburdened public health system having the pressure to manage and treat COVID-19 patients (Kumar & Jeelani, 2020), other health services, including long established ones related to MCH, are being affected. Public Interest Litigation (PIL) filed by activists earlier this month suggest that denial of services is taking place (Pal, 2020). Whether and in what ways MCH service delivery for homeless women is affected, remains unknown. The study will examine the barriers faced by urban homeless women in Delhi in accessing MCH services as a consequence of the outbreak of Coronavirus disease (COVID-19). This study will supplement the ethnography by demonstrating how the pandemic has affected health-seeking of urban homeless women vis-à-vis MCH services. The findings will be useful in informing policy about how MCH services can be streamlined and be made more accessible in the current context, providing critical insights for the PIL as well as for health system actors involved with planning and delivering services to the urban homeless and poor. 2) Aims or research questions being addressed What are the barriers faced by urban homeless women in Delhi in accessing and utilizing MCH services in the wake of public hospitals being overwhelmed with COVID-19 cases? 3) Study Design Qualitative research methods will be used to get an understanding of the present situation of urban homeless women and the challenges that confront them in the wake of the lockdown enforced because of the COVID-19 pandemic. In depth interviews (IDI) will be supplemented by field observations to see the changes that have taken place in the lives of urban homeless women in two field sites in Delhi where the recent ethnography was done. At one field site, women stay with their families under a flyover in temporary enclosures. At another field site, single women stay in pavements or nearby shelters. Key Informant Interviews will be done with activists involved in filing the PIL as well as practitioners involved in advocacy pertaining to arranging food for migrants stranded in cities after the lockdown. We expect to be able to conduct IDIs with 15 women and three key informants. We will be guided by the consolidated criteria for reporting qualitative research (COREQ) guidelines for qualitative research (Tong et al., 2007). Data collection Convenience sampling will be used to speak with women at the field site. Given the contagious nature of the current pandemic, verbal consent procedures will be used. Neither signatures will be taken on paper, nor will verbal consent be recorded. The purpose of the study will be explained to participants in detail, including the risks and benefits of participation. Precautions will be taken to maintain distance from participants to ensure distancing norms so as to safeguard the health of both the interviewer as well as interviewees. After obtaining permission from participants, interviews will be audio-recorded. Data will be stored in password-protected laptops belonging to research team members. A consultant will be hired for transcription of interviews, and asked to sign confidentiality agreement. Data analysis As in the case of the earlier ethnographic research, thematic analysis will be used to interpret findings from fieldnotes and interview transcripts. Atlas.TI software will be used for analysis, with the researcher and her supervisor carrying out coding and iteratively developing and applying a codebook. Analysis will adhere to COREQ and existing standards of quality in qualitative research, including member checking/respondent validation, reflexivity, and fair dealing (Mays & Pope 2000). 4) Approach used to maximise the impact of research outputs, to improve health and the research community This study will be conducted in partnership with our long-term collaborator Centre for Equity Studies (CES), an organization we have collaborated with for the recent ethnography as well. CES runs recovery shelters in collaboration with Delhi Urban Shelter Improvement Board of the Delhi government for ailing homeless women and women. The organization additionally provides mobile van based health services to urban homeless people in several locations in Delhi and other cities in India. In the wake of the lockdown enforced in India in second half of March 2020, members of CES along with other practitioners have been involved with advocacy for the urban poor and migrants who have been displaced as well as working alongside the Delhi government to make arrangements for the distribution of food to urban poor people living in various parts of the city. The findings of our study can therefore be used by CES to improve and streamline their service delivery and support of MCH related health-seeking and service utilisation. Further, we believe their association with the Delhi government will be useful in helping us share the findings of the study with government for its immediate perusal so that action may be timely taken to safeguard the health of urban homeless women. Based on the findings of the study, we will also make a fact-sheet on the needs of the community during the pandemic and carry out dissemination with the organisations involved PIL as well other non-governmental organizations and fund-raising entities working with the homeless and/or urban poor. 5) Expected outcomes The findings will: • Be useful in helping our partner organization, CES, in realigning their current strategies towards prioritizing services for urban homeless pregnant and lactating women. • Add to the evidence base for the urban poor and contribute towards larger subsequent grants to test interventions for improvement of MCH outcomes. • Supplement the PIL by providing evidence for the state government to reorient health services for maternal and child healthcare for urban poor women in public hospitals. 6) Your role in the project The applicant will be engaged in making of interview guide, consent procedures, and in getting the approval from Institutional Ethics Committee. She will also be engaged in data collection, that is conducting interviews, as well as in the analysis of data, and writing of the report, in addition to the subsequent writing of manuscripts. All of this will be done under the supervision of her supervisor, Dr Devaki Nambiar. References Agarwal, P., Singh, M. M., & Garg, S. (2007). Maternal health-care utilization among women in an urban slum in Delhi. Indian Journal of Community Medicine, 32(3), 203. https://doi.org/10.4103/0970-0218.36829 Blas, E., & Kurup, A. S. (2010). Equity, social determinants and public health programmes. World Health Organisation. Diamond-Smith, N. G., Gupta, M., Kaur, M., & Kumar, R. (2016). Determinants of Persistent Anemia in Poor, Urban Pregnant Women of Chandigarh City, North India: A Mixed Method Approach. Food and Nutrition Bulletin, 37(2), 132-143. https://doi.org/10.1177/0379572116637721 Dwarkanath, P., Vasudevan, A., Thomas, T., Anand, S. S., Desai, D., Gupta, M., Menezes, G., Kurpad, A. V., & Srinivasan, K. (2018). Socio-economic, environmental and nutritional characteristics of urban and rural South Indian women in early pregnancy: Findings from the South Asian Birth Cohort (START). Public Health Nutrition, 21(8), 1554-1564. https://doi.org/10.1017/S1368980017004025 Kumar, A., & Jeelani, G. (2020, April 18). Agonising wait for non-Covid patients in Delhi. India Today. https://www.indiatoday.in/mail-today/story/agonising-wait-for-non-covid-patients-in-delhi-1668256-2020-04-18 Office of the Registrar General, India, M. of H. A., Government of India. (2018). Special Bulletin on Maternal Mortality in India 2014-16 (p. 3). Office of the Registrar General, India. http://censusindia.gov.in/vital_statistics/SRS_Bulletins/MMR%20Bulletin-2014-16.pdf Pal, S. (2020, April 23). COVID-19: 'Treat Women's Health as Top Priority,' Delhi HC tells State Government. NewsClick. https://www.newsclick.in/COVID-19-Delhi-High-Court-On%20Women-and-Health Siddaiah, A., Kant, S., Haldar, P., Rai, S. K., & Misra, P. (2018). Maternal health care access among migrant women labourers in the selected brick kilns of district Faridabad, Haryana: Mixed method study on equity and access. International Journal for Equity in Health, 17(1), 171. https://doi.org/10.1186/s12939-018-0886-x Suri, S. (2019, June 5). An analysis of maternal health condition across parliamentary constituencies in India. ORF. https://www.orfonline.org/expert-speak/an-analysis-of-maternal-health-condition-across-parliamentary-constituencies-in-india50535/ Tong, A., Sainsbury, P., & Craig, J. (2007). Consolidated criteria for reporting qualitative research (COREQ): A 32-item checklist for interviews and focus groups. International Journal for Quality in Health Care, 19(6), 349-357. https://doi.org/10.1093/intqhc/mzm042",2021,2021,"George Institute for Global Health, Delhi",6485.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,South-East Asia,South-East Asia,Gender,,,India,India,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C09633,20/048,Assessing the response to the COVID-19 pandemic in Internally Displaced Persons Camp in Northern Nigeria,"Project Title: Assessing the response to the COVID-19 pandemic in Internally Displaced Persons Camp in Northern Nigeria Background Over 2 million people are displaced in Nigeria as a result of Boko Haram Terrorist that have been engaged in an armed conflict with the Federal Republic of Nigeria for close to two decades. Consequently, many migrants live below the poverty line and are at risk of facing dire health consequences due to the fact that many of them are disadvantaged and marginalized. While some studies on the response to the novel coronavirus pandemic among people living with disabilities, individuals in urban settings and among the elderly population, there have been no studies on barriers and drivers to uptake and adherence to preventive public health measures in humanitarian settings such as Internally Displaced Persons (IDP) camps. After searching eight (8) databases (Google Scholar, PubMed, SCOPUS, HINARI, CINAHL, JURN, DOAJ, and Web of Science), I have found no single original study on this area. Knowing about the response to the COVID-19 pandemic in these fragile regions will help in informing public health interventions and policies and will assist these vulnerable communities during the current SARS-CoV-2 pandemic and also for future pandemic and public health emergency response in this region. The priority of this study is supported by a commentary by Dahab and colleagues1 where they identified the following reasons for an urgent response to the pandemic in humanitarian settings such as internally displaced persons (IDP) camps. 1. Increase likelihood of coronavirus transmission due to larger family size, overcrowded IDP camps, poor water and hygienic practices and increased social gatherings 2. Greater chance for the progression of the covid-19 infection to progress to severe condition in these region due to an higer prevalence of noncommunnicable comorbidities eg HIV, TB, malnutrition, etc 3. Greater probability for these vulnerable people to die if they need specialized healthcare services which is not readily available due to lack of intensive care services in these region which are often located outside the major citities.[1] Our focus is to identify both the barriers and drivers to uptake and adherence to prevention public measures such as social distancing, hand washing, etc among the internally displaced persons during the present coronavirus pandemic. The findings of this project will be greatly influential in providing the evidence base needed in national, regional, and continental health policies in the African continent especially during the COVID-19 pandemic and beyond. Also, the project is important in providing great insight into the health burden of vulnerable population in two African countries (Ethiopia and Nigeria) which will provide the necessary evidence for the international non-governmental organization, foreign agencies, multinational companies, philanthropic bodies, and external government agencies to provide funding, support, and partnership to African communities, regions, and countries to help promote health and wellbeing within the great African continent. Research Question What are the barriers and drivers to uptake and adherence to public health prevention measures among internally displaced persons in conflicting regions in Northern Nigeria during the COVID-19 pandemic? Objectives 1. To determine the barriers to uptake of public health prevention measures 2. To investigate the barriers to adherence to public health prevention measures 3. To assess the drivers to the uptake of public health prevention measures 4. To determine the drivers to the uptake of public health prevention measures 5. To assess the effectiveness of developed tools and evidence-based strategies and tools that can enable uptake and adherence to prevention measures in humanitarian settings STUDY DESIGN and Approach Used to Maximise Research Output A mixed-method cross-sectional study will be utilized in order to ensure the collection of both comprehensive quantitative and qualitative data on the topic of interest. Participants would be chosen across internally displaced persons' camps in northern Nigeria using a multistage sampling technique. The list of the IDP camps to be used for the study in the chosen regions would be chosen randomly using a combination of systematic random sampling and simple random sampling (fish bowl technique). While participants for the quantitative part of the study would be selected via consecutive random sampling, participants for the qualitative part would be recruited from the quantitative one that was earlier done to further explore the situation, as those interested would be encouraged to indicate interest. A minimum of 700 participants would be recruited for the qualitative component and 50 for the qualitative component. The qualitative component will involve 7 focus group discussions (involving a maximum of 6 people) and 15 Key in-depth/informant interviews. Qualitative data would be collected (with the help of 4 trained research assistants) through the use of questionnaires adapted from similar gold standard questionnaires with very good psychometric properties, on the uptake, and adherence to preventive measures for infectious diseases. Also, the focus guide along with the guide for the KII would also be prepared from similar ones in high-impact journals. Additionally, tools would be created in consultation with stakeholders and key organizations working with migrants and refugees. Face validity, content validity, inter-rater and intra-rater validity of the developed tools would also be assessed by the research teams. The key variables would include sociodemographic characteristics (age, sex, religion, location of the camp, occupation, marital status, financial status, etc). The questionnaires plus focus and key informant interview guide would also assess for factors responsible for uptake and adherence to preventive measures along with the barriers. Analysis Plan The qualitative data from the Focused group discussion and Indepth interviews would be analyzed thematically using Nvivo software. Quantitative data would be analyzed using both descriptive (mean, mode, standard deviation, charts, maps) and inferential (confidence interval, chi-square, independent T-test, Kruskawalis (ANOVA)) statistical tools using Microsoft Excel, Epi Info (for data entry majorly), and SPSS software. Expected Outcome 1. Identification of barriers and drivers to both uptake and adherence to public health preventive measures by internally displaced persons 2. Development of support for the public health response to individuals living in humanitarian support during the current COVID-19 pandemic an also for future epidemics, pandemics, and other public health emergencies 3. Development of a sound and solid research paper to be published in a very high impact journal such as JAMA, The Lancet, BMC journals that will be easily accessible to governmental agencies, NGOs, donors, etc to facilitate appropriate and evidence-based response to individuals in humanitarian settings Further outcomes 1. These findings of this study would be published as an original research in a high impact journal such as The Lancet. Hence, it can be used in systematic reviews and meta-analysis that inform decisions. Also, being in a high impact journal, it will be easily accessible to policymakers and stakeholders working in the humanitarian field can make use of it for various advocacy, research, and innovation projects. 2. Also, our research and study will greatly contribute to policy development at the community, state, national and continental levels. 3. Also, it will help the government, international NGOs, foreign agencies, philanthropic bodies and corporations know how best to support and aid vulnerable communities to prevent the community spread of the COVID-19 virus and also for future pandemics. MY ROLE IN THE STUDY I will be the Principal Investigator (who will work and report regularly to my supervisor) where I will be recruiting, training, and supervising research assistants and other research team members on this project. I will also be involved in writing for ethical approval from the Ethics Review Committee in Nigeria, and I will also be directly be involved in the data collection (qualitative and quantitative) data collection, data analysis and report writing about the research project. Furthermore, I will be involved in the publication and dissemination of research findings to the State and Federal Ministry of Health in Nigeria, NGOs, humanitarian agencies, foreign bodies, and philanthropic organizations who work in humanitarian settings in Nigeria. I will be majorly involved in writing the manuscripts for publication in a high-impact journal such as The Lancet, BMC, JAMA, among others. Reference: 1. Dahab M, Zandvoort K, Flasche S, Warsame A, Spiegel PB, Waldman RJ, and Checchi F. COVID-19 control in low-income settings and displaced populations: what can realistically be done? http: https://www.lshtm.ac.uk/newsevents/news/2020/covid-19-control-low-income-settings-and-displaced-populations-what-can",2021,2020,Slum and Rural Health Initiative,6525.8,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09634,20/056,Implementing behavioral adaptation to curtail transmission and mental health impact of COVID-19 in Internally Displaced People (IDP) camp in Ethiopia,"1. Project background, context and need addressed The world is facing unprecedented COVID-19 global pandemics. Africa is anticipated to be the next epicenter of COVID-19 pandemics according to the WHO. Given the fact; poor healthcare facilities and scarcity of resources, the COVID-19 outbreak can overwhelm the shaky health services (WHO, 2020). Ethiopia has reported 116 cases of COVID-19 so far by April 22, 2020. Though this number is quite small, it is doubtful to rely on as the number of daily testing is low and stringent preventive measures have not done. Thus, there would be a probable surge of COVID-19 up to 28 million infections in Ethiopia according to the ministry of health model prediction (Ethiopian Public Health Institute report, 2020). Ethiopia is the home to more than 3 million displaced people caused by conflicts which makes one of the leading countries with internally displaced people (IDP) (Relief web international 2019). More than 90,000 people were internally displaced in the Amhara region in 2019 due to longstanding conflict between the Amhara and Qemant communities (IOM displacement report, 2019). The majority have returned to their normal settlement with the peace-deal process between the two communities. Still, 15, 000 IDP are living in various local camps, communal accommodation sites, and collective sites with a high risk of protection concerns because of overcrowded shelter and poor living conditions. Among these, nearly 2,500 people are living in ten small clusters of temporary shelters ranging from 100 to 500 people in the Metema district. (Interagency Rapid Protection Assessment - Gondar, Amhara Region). The IDP's socioeconomic status may negatively impact their ability to take all precautionary measures against COVID-19 and to receive medical care if contaminated. IDP face immense barriers to accessing healthcare and preventative services like proper hand-washing and sanitation facilities. So, when an infectious disease hits, their risk is compounded and would result in catastrophic health and psycho-social consequences (IOM, 2020). Besides to prevention of the outbreak, particularly in highly vulnerable people like IDP's in the humanitarian setting monitoring and reporting rates of anxiety, depression, self-harm, suicide, and other mental health issues are crucial to understand and inform interventions. The rise in symptoms of anxiety and coping responses to stress are expected during these extraordinary circumstances, the number of people with anxiety, depression, and engaging in harmful behaviors (such as suicide and self-harm) will increase. (Emily A Holmes et al, Lancet 2020). The unprecedented occurrence of the COVID-19 pandemics and living with insecurity conditions could devastate the underlying psycho-social well-being of displaced people. Consequently, those highly vulnerable people require tailored responses both to the pandemics and mental health services. Implementing temporary behavioral adaptation, psychological first aid, and consultation to new ways of lifestyle such as emotional support, frequent hand-washing, sanitizer use, and social distancing measures would be helpful to prevent the outbreak of COVID-19 and associated mental health impairment in overcrowded settings. Furthermore, wearing a cloth face-covering may help to protect the most vulnerable from COVID19. Though face- covering cannot be equivalent to self-quarantine, social distancing, and medical face-masks; it may protect the transmission in an asymptomatic carrier of the corona-virus especially in overcrowded conditions (CDC, 2020). Refuge and humanitarian camps are under overcrowded conditions and vulnerable to a high rate of infection transmission. Therefore, in such inevitable circumstances, prevention of the outbreak and implementing feasible behavioral adaptation as voluntary public health measures like washable and reusable handmade face-mask use, frequent hand washing, and sanitizer use could be indispensable when resource-intensive public health measures are not affordable. 2. Aims or research questions being addressed The main aim of this study is to investigate the effectiveness of temporary behavioral adaptation as a voluntary public health measure to curtail the transmission and psycho-social impact of COVID-19 pandemics in IDP at the humanitarian setting in Ethiopia. The specific objectives include:  Explore the baseline behavioral practice and psycho-social status of IDP towards COVID-19 at their temporary camps  Provide comprehensive behavioral adaptation advice, sanitation logistic support, and psychological first aid  Document the number of people referred for tests, cases and mental health complaints of IDPs at the campsites  Evaluate the effectiveness of behavioral adaptation implementation and psychological support in IDPs to prevent COVID-19 outbreak 3. Study Design Study setting Metema is located 900 km away from Ethiopia's capital, Addis Ababa. It has an international boundary of 60 km between Ethiopia and Sudan. Its location makes it one of the high-risk areas to acquire the virus for the COVID-19 outbreak. Therefore, IDP living in the area is subjected to multiple risk factors such as living in overcrowded unsanitary camps, unstable seasonal Malaria areas with a high risk of Leishmaniasis co-infection. The majority (87.3%) of the displaced people have mobile phone devices (UNHCR Ethiopia report, 2019). This could make it easy to provide telephone reminders and weekly telephone consultations to comprehensive educational support, psychological reassurance, and intervention assessment. Method and Materials One small cluster camp of 100 IDP from the 10 camps in the Metema district will be selected randomly and enrolled in this action research project. Multifaceted interventional approach consisting of onsite behavioral training and logistics support, telephone reminders, weekly telephone consultation, and psychological support will be employed. In the first phase of the study, a combination of qualitative and quantitative approaches using descriptive and analytical study designs will be employed to explore the baseline understandings, extent and appropriateness of safety practices to COVID-19 prevention. An in-depth interview will be employed to generate information regarding their awareness, psycho-social status, and preparedness to personal safety measures to COVID-19. This prior assessment of the knowledge and practice gap will help to customize educational delivery and material support. In the second phase of the study, a customized 1-hour hands-on comprehensive adaptive behavioral awareness and training will be delivered at the campsite with some hygiene logistics support. Training on how to make cloth face-mask, wear, and wash for reuse will be provided. Then after, an individual automated telephone alarm before the call (a reminder of the disease transmission, safety measures, and practices), weekly telephone comprehensive advice, psycho-social first aid, and mental health support for those in need will be employed. Weekly telephone surveillance of symptoms for possible infection will be collected from onsite humanitarian workers and will link to the nearby COVID-19 test center. In the final phase of the project; the effectiveness of behavioral adaptation intervention as a voluntary public health measure to prevent the transmission, psycho-social and mental health impacts will be evaluated by predetermined quantitative checklists and qualitative methods. Generally; to conduct this multifaceted action research the following materials and logistics support will be prepared.  3-page COVID-19 brochure consisting of pictograms and factual data regarding COVID-19 mode of transmission, symptoms, safety measures, and social distancing instructions  Sanitizer, hand-washing soap, reusable and washable handmade face-covering mask  Capacity building training of data collector's and humanitarian workers  Mobile air time for a telephone consultation  The WHO standardized mental health status examination questionnaire, Quantitative behavioral adaptation checklists, and Qualitative informant questions 4. Approach used to maximize the impact of research outputs, to improve health and the research community While quantifying and generating practically tested evidence from this project, the multifaceted interventions comprised of comprehensive behavioral education, psychological support, and regular telephone alarming expected to prevent infection transmission and improve the health of the study participants. Furthermore, it involves health workers, psychiatry professionals, and humanitarian workers to provide behavioral support and training, psychological first aid, and gather evidence. The evidence of this study will be disseminated for the ministry of health, local health authorities, and to humanitarian organizations and international refugee agencies. This would be instrumental to provide a tested feasible behavioral adaptation model as a voluntary public health measure in the prevention of infectious disease outbreak in similar overcrowded and humanitarian settings. Finally, it will be published in the peer-reviewed journal for sharing the evidence with the scientific community and the wider public. 5. Expected outcomes  Humanitarian assistance (including behavioral education, psychological and material support) and inculcated behavioral adaptation practices for prevention and coordination of COVID-19 outbreak response in the humanitarian camp of IDP  The quantified measure of behavioral adaptation effectiveness to prevent transmission  The qualitative and quantitative measure of psychological support effectiveness to reduce mental health problems during a pandemic  Documentation of the frequent psychological and mental health problems in IDP  Epidemiological evidence and practical lessons of comprehensive interventional COVID-19 prevention from the small cluster of IDP perspective to the scientific community. 6. Role in the project I am the principal investigator who conceived the study and responsible for carrying most of out the activities under supervision. Among the roles, I am developing appropriate study design, prepare educational content and interventions. I will participate in recruiting and train humanitarian workers and data collectors to provide interventional education. I will also evaluate the intervention effectiveness, analyze and interpret data, disseminating the research output through presentation and feedback for relevant stakeholders. Finally, I will prepare and send the final manuscript for publication.",2021,2020,University of Gondar,6699.33,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Ethiopia,Ethiopia,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09635,20/064,PROPORTION AND CHARACTERISTICS OF COVID-19 SUSPECTS AMONG BLOOD DONORS IN NORTHERN TANZANIA,"BACKGROUND, CONTEXT AND NEEDS The emergency of the Sar-Cov-2 about 5 months ago found most places in the world to be unprepared for this unprecedented crisis. The result is a significant increase of number of infections and the corresponding mortality associated with it. By mid of April, 2020, its estimated that more than 2,094,725 people have already been infected with more than 135,562 (6.5%) deaths, and only 520,930 (24.8%) who have recovered. Tanzania is not an exception with the number of infections and deaths keeping on increasing. Due to its notorious nature of transmission, the pandemic has expressively affected the economical, social and political decisions of the communities at large and individuals in particular. This aspect has seriously affected the struggle to have a continuous supply of adequate and safe blood and blood components. Several strategies have been recommended by the World Health Organization (WHO) so as to ensure availability of adequate and safe blood as well as ensuring the safety of blood donors, blood recipients and staff of Blood Transfusion Service (BTS), during an infectious disease emergency (WHO 2019, WHO 2020). These strategies have been widely applied during blood donation in different settings during this pandemic (Chang et al. 2020, Xiaohong et al. 2020). Some of these strategies include screening for fever for all potential blood donors and appropriate use of personal protective equipment (PPEs) such as masks, gowns and sanitizers as well as frequent hand washing with soap and clean water. Others include maintaining social distance of 1 to 2 meters, reduction of waiting time for blood donors, as well as introducing additional screening questions to exclude donors who have/had a recent positive SAR-Cov-2 infection or had an exposure to a patient who had a positive SAR-Cov-2 diagnosis. Transmission of SAR-Cov-2 through blood transfusion is theoretically possible (Chang et al., 2020) but no objective evidence has yet been obtained (references). This does not eliminate the crucial need of strict screening for SAR-Cov-2 and immediate disposal of infected blood before its use(references). With the current SAR-Cov-2 pandemic, Tanzania has introduced the WHO recommended measures on its blood collection protocol so as to reduce the risk of transmission of the disease. Due to reduced capacity of testing for SAR-Cov-2 and reduced awareness and willingness for testing, the active involvement of BTS in early detection of SAR-Cov-2 suspects among blood donors, and to defer them from blood donation and refer them to get appropriate care is crucial. The practice will help prevent the spread of SAR-Cov-2 and reduce the burden of the disease. This study will determine the proportions and characteristics of those deferred from blood donation due to potential or valid exposure to SAR-Cov-2. It will also highlight the potential magnitude and impact of SAR-Cov-2 in the general population and specifically the blood donors. STUDY AIMS AND RESEARCH QUESTIONS RESEARCH QUESTION What is the proportions and characteristics of patients deferred due to being suspects of SAR-Cov-2 during blood donation in Northern Tanzania? SPECIFIC OBJECTIVES 1. To determine the proportion and characteristics of blood donors deferred due to fever 2. To determine the proportion and characteristics of blood donors deferred due to history of travel to COVID-19 area in the past 28 days 3. To determine the proportion and characteristics of blood donors deferred due to exposure to COVID-19 infected patient in the past 28 days 4. To determine the proportion and characteristics of blood donors deferred due to COVID-19 infection in the past 28 days 5. To determine the proportion of blood units discarded after the blood donor becomes SAR-Cov-2 suspect after a blood unit has already been donated STUDY DESIGN AND METHODOLOGY DESIGN A cross-sectional study whereby all blood donors who donated blood after the commence of the study will be included for analysis STUDY SETTINGS AND POPULATION The study will involve blood donors who donated blood during the study period from July 2020 to June 2021, in Northern Tanzania. VARIABLES Predictor /Independent variables: Age, sex, place of domicile, type of blood donor (voluntary, family replacement, first time or repeat). Outcome /Dependent variables: Being suspect or confirmed case of SAR-Cov-2 infection STUDY PROCEDURES All blood donors will undergo routine demographic and medical screening to establish their eligibility for blood donation. But before this a special SAR-Cov-2 screening will be done using a special designed questionnaire form. All suspected individuals will be deferred from blood donation and referred to the appropriate health care facility for further investigations and management. Those screened negative in all screening procedures, will be allowed to donate blood, but a follow up phone call will be made to each donor after 3 days to rule out a diagnosis of SAR-Cov-2 infection to the blood donor. If the blood units will still be in the BTS premises the blood units will be discarded, but if the blood units will have been transferred to the health facility for use, information will be sent immediately to the relevant health facility authority. ETHICAL CONSIDERATION Ethical clearance will be sought from National Institute of Medical Research (NIMR) -National Health Research Ethical Committee or Kilimanjaro Christian Medical University College-Clinical Research Ethical Committee. Permission from MoH and NBTS authority to conduct the study will also be sought. Blood donors' data will be kept confidential, and privacy will be strictly observed throughout the study. APPROACH TO MAXIMIZE IMPACT OF THE RESEARCH OUTPUTS The following activities will be done to maximize the impact of the research outputs: • The manuscript will be prepared and submitted for publication in an international journal • Findings will be presented to staff of the National Blood Transfusion Services (NBTS) and the Ministry of Health for further discussion and improve the way forward when needed. The aim is to improve availability of safe and adequate blood so as to improve health. • Findings will be presented at the Academic Forum of the Kilimanjaro Christian Medical University College (KCUMCo), and a copy be kept in the KCMUCo library, to increase awareness on the topic to research community EXPECTED OUTCOMES The study will help us estimate the magnitude of the burden of Coronavirus infectious outbreak on availability of adequate and safe blood. It will also help us to characterise the blood donors suspected of Coronavirus infection/exposure. This will inform us on the way forward to tackle the problem. REFERENCES Chang L, Zhao L, Gong H, Wang Lunan, Wang L. Severe acute respiratory syndrome coronavirus 2 RNA detected in blood donations. Emerg. Infect Dis 2020 Jul; 26(7). Le Chang, Ying Yan, Lunan Wang. Coronavirus Disease 2019: Coronavirus and Blood Safety. Transfusion Medicine Reviews 21 February 2020 WHO, 2019. Protecting the Blood Supply During Infectious Disease Outbreak WHO, 2020. Maintaining a safe and adequate blood supply during the pandemic outbreak of coronavirus disease (COVID-19). An Interim guidance Xiaohong Cia, Min Ren, Fenghua Chen, Liliang Li, Hang Lei, Xuefeng Wang. Blood transfusion during the Covid-19 outbreak. Blood transfus. 2020 March; 18(2):79-82 MY ROLE IN THE PROJECT : PRINCIPAL INVESTIGATOR",2021,2021,Ministry of Health Tanzania,6700,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Tanzania,Tanzania,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09636,20/068,Perceptions and adherence to preventive measures for Coronavirus Disease 2019 among rural communities in Uganda,"1) Project background, context and needs addressed The Coronavirus Disease 2019 (COVID-19) pandemic has spread to over 205 countries and territories globally with over 2 million confirmed cases and 140,000 deaths. Africa has the least burden of confirmed cases but is expected to rise exponentially. Uganda has so far registered 74 confirmed cases, and 9% are locally transmitted. COVID-19 is spread from person to person through respiratory droplets and contact with contaminated objects. In the absence of effective treatment or vaccines, governments worldwide have opted for non-pharmaceutical interventions. Low-income countries such as Uganda may not be able to manage exponential increases in COVID-19 cases because of weak health systems. Consequently, the Government of Uganda has implemented stringent preventive measures for the disease which are largely behaviour-based. These measures include frequent hand washing with soap, physical distancing, self-quarantine for those with symptoms, avoidance of non-essential travel, avoiding contact with the eyes, nose and mouth, and staying home . Information on these measures has been communicated to the general public through mass media platforms such as televisions, radios, newspapers and social media. Messages have taken on various forms such as songs, presidential directives and ministerial speeches. Rural communities of Uganda are home to over 75% of the population who are largely poor with limited access to health services. These communities have lower literacy rates, limited access to electricity and smart phones, and majority cannot afford internet services. In addition, the communities are usually hard-to-reach, have poor telecommunication network, and as such may have limited access to information on COVID-19 prevention. Another challenge faced by rural settings is limited access to safe water and soap which may reduce their adherence to personal hygiene measures. High numbers of people living per household in rural communities may reduce adherence to physical distancing. Studies currently being conducted in Uganda on the adherence to COVID19 measures are majorly web-based and use self-administered questionnaires. Consequently, these studies exclude residents of rural communities by enrolling only participants with access to a computer or smartphone, internet and with high literacy levels. This study therefore aims to understand the perceptions and adherence to COVID-19 preventive measures in the midst of the challenges associated with living in rural Uganda. 2) Aims or research questions being addressed Broad objective To assess community perceptions and adherence to COVID-19 preventive measures in rural Wakiso district, Uganda in order to provide essential information needed by public health officials and other stakeholders to make an informed decision on the most effective strategy for reduced transmission. Specific objectives 1. To establish community perceptions towards COVID-19 preventive measures. . 2. To assess community adherence to COVID-19 preventive measures as issued by the Government of Uganda. 3. To explore community barriers and facilitators of adherence to COVID-19 preventive measures. 3) Study design Methods Study design The study will be a community-based cross-sectional study that will involve both quantitative and qualitative methods. A semi-structured questionnaire will be used to collect data on specific objectives 1 and 2. An observational checklist will be used to collect data on specific objective 2. A Focus Group Discussion (FGD) guide and Key Informant Interview (KII) guide will be used to obtain data on specific objective 3. Study Area The study will be carried out in Wakiso district located in central Uganda. It is the most populated district in the country with a population of 1,997,418 as per the 2014 census, and has 8 constituencies. Consequently, the district was chosen as an appropriate site because of its largely rural population. A recent report for the district shows 38% of households had no access to electricity, illiteracy rate at 9.5% among persons aged 18 years and above, and the most common occupation being subsistence farming (65%). The average household size is 4.7 with 47% households resided in dwellings with only one room for sleeping. In the district, 30.2% of household members are aged at least 10 years and 31% of households have no member with a mobile phone. Radio remains a dominant (65.3%) source of information to the households, 24.6% of persons aged at least 10 years use internet, 62.8% of households have access to drinking water while 12.0% of households own a computer. Study duration 12 months Sample size calculation and sampling Using the formulae for cross sectional studies, assuming a sampling error of 5%, and a statistically conservative prevalence of 50% adherence to COVID-19 preventive measures (COVID -19 is a new disease therefore there are no previous studies carried out on this subject in Uganda), a final sample size of 385 participants was obtained. 4 parliamentary constituencies will be randomly selected from the 8. 2 rural sub-counties will be randomly selected from each of the 4 constituencies. From each sub-county, 2 villages will be randomly selected. From each village, households shall be selected by systematic random sampling. Within a household, the household head or an adult above 18 years in the absence of the household head will be involved in the study. Data collection At each household, data will be collected using a semi-structured questionnaire and observational checklist by trained research assistants with proficiency in Luganda, the local language mostly used in Wakiso district. Respondents will be asked questions on: knowledge on COVID-19; perceptions on COVID-19 preventive measures such as individual susceptibility, effectiveness of preventive measures, belief in government; level of adherence to COVID-19 preventive measures such as social distancing, staying at home, hygiene measures, self-quarantine when with symptoms, avoidance of unessential travel; assess the determinants of adherence such as age, sex, socio economic status, gender, size and household composition, level of education, communication channels, culture, and accessibility to water and soap; coping mechanisms such as water storage, bulk buying, alternative sources of disinfectants. An observational checklist will be used to observe type, functionality and usage of handwashing facilities as well as presence of soap. Data collection tools will be pretested in a rural village within Wakiso district that will not be part of the study sites. During pretesting, validity and reliability of individual questions in the questionnaire will be assessed. For the qualitative component, 6 FGDs will be conducted among community health workers (front line health workers based in the community) in 4 constituencies. 12 KIIs will be conducted among local leaders, health practitioners, religious and cultural local leaders, and district health authorities. Respondents will be asked questions on barriers and facilitators adherence to COVID-19 preventive measures such as political will, availability, affordability and accessibility to enabling environmental factors, and coping mechanisms. Data collection will be supported with FGD and KII guides, which will be developed in English, and translated to the local language. Data management and analysis Quantitative data will be examined and cleaned on a daily basis during data collection and will be entered in EpiCollect5. Data will be exported to Stata 15 software for analysis. Qualitative data will be audio recorded, transcribed, translated (where necessary) and analysed using thematic analysis with the help of Atlas ti. Ethical considerations Ethical approval for the study will be obtained from the Makerere University School of Public Health Higher Degrees, Research and Ethics Committee, and registration at the Uganda National Council for Science and Technology. Participation in the study will be voluntary. Consent and confidentiality The reason for the study will be explained to participants in simple clear terms and in a language they understand best after which a written consent will be obtained prior to the start of data collection. Participant names will not be recorded, and data will be stored and backed up on drives that are passcode-protected which only the principal investigator will have access. 4) Approach used to maximise the impact of research outputs, to improve health and the research community • Stakeholder involvement from the early stages of the research to create ownership. Stakeholders will include from Ministry of Health, Wakiso District Health Office, and village / local council chairpersons, health workers from surrounding health facilities, and influential persons such as religious and cultural leaders. • Dissemination of findings to all stakeholders (listed above). • Dissemination of findings to the study areas through a community dissemination workshop and community radios. • Publication of findings in an open access peer-reviewed journal, blogs, newspaper articles and presentations in conferences and seminars. • Open access to data sets for future secondary analysis. 5) Expected outcomes • To provide essential information that will be used to design interventions related to recommended preventive measures for COVID-19 among rural communities in Uganda. • Results will be used for future planning in case of other related epidemics and pandemics. • Information will be used to advocate for the most effective strategy for reducing transmission of COVID-19 and related viruses in rural areas in Uganda. 6) Your role in the project • I will be the principal investigator therefore involved in overall project oversight with supervision from Dr. David Musoke (my immediate supervisor at Makerere University). • Specifically, I will be involved in conceptualization of the study, data collection, data entry and analysis, manuscript writing and dissemination.",2021,2021,Makerere University School of Public Health,6700,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09637,20/085,Engaging and empowering communities in responding to COVID-19 in low resource countries: A case study of Ghana,"The control of epidemics and pandemics such as the coronavirus disease 2019 (covid-19), remain a challenge to the global community's efforts toward achieving the set targets of sustainable development goal 3 (SDG 3) - ensure healthy lives and promote wellbeing for all at all ages (Galati, 2015, Sundewall and Forsberg, 2020, United Nations, 2020). Even more developed countries, which were thought to have stronger health care systems have experienced challenges in their response to covid-19. The effect of global pandemics tend to be greater on Sub Saharan Africa, because of limited workforce and other resources available to already overstretched and weak health care systems. Additionally, poverty, illiteracy, ignorance, socio-cultural beliefs and practices are rife. Such factors contributed to community distrust of the health care system and sometimes poor cooperation resulting in high rates of infections and the loss of several thousand lives in the Ebola outbreak in Sierra Leone, Liberia and Guinea in 2014 - 2015 (Phillip, 2014, Wang et al., 2020). Sub Saharan African countries like Ghana need to strengthen community engagement and empowerment in health delivery, to ensure early and timely delivery of services, curbing widespread infections, reducing stress on health care systems and saving lives, which will accelerate achievement of SDG3 (Hanson et al., 2017). Ghana introduced the community-based health planning and services (CHPS) concept in 1997, to support its relatively weak health care system. The aim of CHPS is to mobilize community leadership, decision making systems and resources in a defined catchment area, the placement of reoriented frontline health staff with logistic support and community volunteer systems to provide services according to the principles of primary health care (Frimpong, 2020). Subsequently the Ghana Health Service and its partner organisations have established CHPS compounds in most districts in Ghana to offer primary health care in communities. The CHPS facilities are under the Ghana Health Service, which is the government's health service provision agency. Currently, Ghana has 1,550 convid-19 cases with 10 deaths (Ghana Health Service, 2020a). Government's strategy in combatting covid-19 include closure of Ghana's boarders with her neighbours, general surveillance, enhance contact tracing, health education and treating cases (Ghana Health Service, 2020b). There have been anecdotal reports of developments that are currently hampering government's efforts in combating covid-19 such as resistance of community members to contact tracing and testing. Stigmatization of covid-19 victims and survivors and outright refusal by some communities to allow government to use public buildings sited in their locality as quarantine centres (Darko, 2020, Ghana Web, 2020a, Ghana Web, 2020c). Also, community leaders have bemoaned government's failure to engage them in the fight against covid-19 (Ghana Web, 2020b). This raises concerns on why government's efforts at using CHPS to engage and empower communities has not yielded the desired results in the fight against covid-19. 2) Aims or research questions being addressed Research Goal To explore and understand how the Ghana health service has engaged and empowered communities to support the fight against convid-19. Specific objectives • To understand how the Ghana Health Service has engaged and empowered communities in the fight against covid-19 • To understand the gaps in the engagement and empowerment efforts of communities in the fight against convid-19 • To explore innovative ways that the Ghana Health Service can employ to improve engagement and empowerment of communities to respond to the fight against covid-19 and other infectious diseases Research questions • How has the government engaged and empowered communities in the fight against covid-19? • What have they engaged communities on? • What has been the response of communities? • How can the challenges in engaging and empowering communities be addressed to support their work? 3) Study design The study design will be ethnographic using indepth interviews (IDIs), focus group discussions and observations in two communities. Ethnographic qualitative design is the appropriate approach for this study, as the study seeks to understand behaviours such as communities' interactions with the Ghana health system, communities' experiences in empowerment processes and their response to the fight against covid-19 (Patton, 2002). Two communities with CHPS compounds would be purposively selected for the study and one community under each CHPS compound will be purposively selected for the study. In each CHPS compound two frontline staff will be purposively selected to participate in the IDIs. Two Ghana Health Service managers from the study district will be included in the study. Twenty-four IDIs will be conducted, 12 in each community with chiefs, elders etcetera (the list below gives the breakdown). They will be purposively selected for face-to-face IDIs, which will seek to understand how the health system has engaged and empowered communities in the fight against covid-19. Focus group discussions will be conducted with women, men and adolescents on the same theme. The focus group discussions would consist of 6 to 13 participants, who would be purposively selected to participate. Participation will be voluntary and those who are not interested would be automatically excluded, as well as those who are mentally challenged. Observations would be carried out in key public places to identify community resources. List of data collection methods and categories of respondents Ghana Health Service level IDIs FGDs District officials 2 - Frontline staff 4 - 2 Communities Chiefs 4 - Elders 4 - Women - 4 Men - 4 Young people - 4 Religious leaders 4 - Herbalists 4 - Assembly persons 4 Total 28 16 The study will be conducted in the Ketu South Municipality of the Volta Region of Ghana, because currently it has the highest number of 6 out of the 10 covid-19 cases in the region. The Municipality also shares boundaries with the Republic of Togo to the east, which makes it to a very interactive district. The population of the Municipality according to 2010 population and housing census stands at 160,756 with 75,648 males and 85,108 females (Ministry of Local Government and Rural Development, 2006, Wikipedia, 2019). Data management Interviews and observation notes will be recorded using a digital recorder. The recorders and the transcribed data will be anonymized and accessible only to the study team and will be used only for the purposes of the study. After the study the anonymized data sets would be uploaded onto the UHAS data sharing portal and will be made available to students for academic work. Data analysis: Transcribed data (IDIs, FGDs, observation notes) will be uploaded onto a computer and transferred onto qualitative software NVivo 12 to support data coding and analysis. Thematic analysis will be conducted, which will form the basis of reporting study results. Ethical issues: All ethical procedure will be followed. The protocol will be submitted to the University of Health and Allied Sciences' ethics review committee for approval. Selection and participation in the study will be purely voluntary. 4) Approach used to maximise the impact of research outputs, to improve health and the research community The approach that would be used to maximise research output will be as follows: • Publication of at least two articles from the study in open access journals • Development of policy briefs that will be shared with the Ghana Health Service, CHPS compounds, the department of infectious diseases of Ghana and it will also be posted on the Institute of Health Research of the University of Health and Allied Sciences website • The study results will be disseminated at local and international conferences • Durbars, which are open air meetings, will be organized to share the results with community members • Dissemination workshops would be held with health workers and managers in the study district to share the findings with them • The results would be presented at the Institutes' monthly technical meetings 5) Expected outcomes The following are the expected outcomes: • The results will contribute to understanding the extent to which the government has engaged and empowered communities in the fight against covid-19 • Challenges in community engagement and empowerment would be identified and recommendations to address them would be proposed • The results would reveal community response to government's engagement and empowerment efforts in their fight against epidemics and global pandemics such as covid-19 in Ghana • The results will unearth strategies to strengthening engagement and empowerment of communities to support the Ghana health care system in fighting diseases such as covid-19 within communities • The results could support policy revisions of community engagement and empowerment approach currently being applied in Ghana 6) Your role in the project The study will involve a team of five researchers: a supervisor, a principal investigator and three field assistants. My role will be the principle investigator, which will include designing the study protocol and study guides, training of field assistants, leading the research team in data collection, analyzing the data gathered, drafting the results into publications, developing policy briefs and presentations and writing and coordinating the dissemination process. I will also liaise with the funders to update them on the developments of the study. Selected reference DARKO, K. A. 2020. 2 Covid-19 patients at Old Fadama on the run [Online]. Accra: Joy Online. Available: https://www.myjoyonline.com/news/national/2-covid-19-patients-at-old-fadama-on-the-run/ [Accessed 12/04/2020 2020].",2021,2021,University of Health and Allied Sciences,6450,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Ghana,Ghana,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Policy research and interventions | Indirect health impacts,2020 +C09638,20/086,Optimizing the World Health Organization guidelines for health care workers' protection from COVID-19 in East Africa: an implementation research study,"1. Background: In November 2019, Wuhan, China was the epicenter of an outbreak of cases of pneumonia of unknown origin (Zhou et al., 2020). Early in January 2020, Chinese scientists isolated the novel virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) in patients with pneumonia (Kim et al., 2020). Later in February 2020, World Health Organization (WHO) designated the clinical syndrome as coronavirus disease 2019 (COVID 19) (WHO, 2020). COVID 19 is responsible for a wide spectrum of illnesses ranging from asymptomatic infection to severe pneumonia causing respiratory failure and fatal deaths. As of 18th April 2020, WHO reported 2,160,207 confirmed cases globally and 146,088 deaths attributed to COVID 19 (Practice, 2020). In one study of patients admitted with confirmed SARS-COV-2 infection, the overall in hospital mortality was 28% (Zhou et al., 2020). Notably, 48% of the deaths occurred in patients with co-morbidities such as hypertension, diabetes and coronary heart disease (Shi et al., 2020; Wu et al., 2020; Yang et al., 2020; Zhou et al., 2020). Some of the lessons learnt at this point in the pandemic include the value of taking extraordinary measures such as complete lock-down, tracing and testing contacts and major quarantine restrictions (Bong et al., 2020). However, the outbreak continues to escalate throughout the world causing unprecedented challenges in the healthcare systems. While millions worldwide are advised to stay at home to abate transmission, health care workers (HCWs) are preparing to do the opposite. Reports from China indicating 3,300 HCWs were infected in early March 2020 and of these, 18 died by the end of February 2020 (SU., 2020). The story is the same in Italy and the United States (US) (The Lancet, 2020; Weise, 2020), reinforcing apprehensions that the nation's frontline defense is now becoming especially vulnerable to the virus. Protecting HCWs is crucial. During the severe acute respiratory syndrome (SARS) outbreak in 2003, approximately 1,725 HCWs were infected (Dena and Darryl, 2004). Risk factors for SARS-CoV-2 infection in HCWs include involvement in procedures generating aerosols such as intubation, working longer hours >10 hours/day, and suboptimal hand hygiene (Ran et al., 2020). As the virus spreads into Africa, it is anticipated that facilities will be overwhelmed not only with patients suffering from COVID-19, but also from other known endemic diseases such as HIV, tuberculosis and malaria. Due to shortages in human resources for health, we expect that HCWs will be required to work long hours under considerable pressure. International guidelines that recommend N95 respirators and gowns may not be implemented due to resource limitations (WHO Global Infection Prevention and Control Network, 2020; World Health Organisation, 2020). As WHO has recommended, implementation research is urgently needed to identify the best strategy for preventing SARS-CoV-2 infection in HCWs in hospitals in Africa where resource limitations prevents adaptation of the international guidelines (WHO Global Infection Prevention and Control Network, 2020; World Health Organisation, 2020). We therefore aim to adapt the existing WHO COVID- 19 guidelines and develop an adopted guideline to protect HCWs from COVID 19 at Bugando Medical Center in Northwestern Tanzania. 2. Research question: What is the best strategy to protect health care workers from COVID-19 in North Western Tanzania? Objective: To develop and optimize guidelines to protect HCWs from COVID-19 at Bugando Medical Center using resources available in Tanzania. Hypothesis: The best strategy for preventing HCWs from developing COVID-19 will involve: 1. Careful hand washing with soap and water with monitoring and supervision at handwashing stations 2. Universal masking of healthcare workers from entry to the hospital campus until departure 3. Use of hospital scrubs with a dedicated changing area 4. Reducing out-patient clinic visits (each specialist seeing at least 5 patients) 5. Providing clothed masks for all patients prior to entering the hospital 6. Visiting hours reduced to once a day instead of twice a day 7. One relative per patient allowed during visiting hours 8. Preparing a designated room in all wards for a COVID suspect 9. Ensuring all in-patients are screened (with a questionnaire) prior to usual assessment. 10. All elective surgeries should be postponed 11. Weekly Continuous medical education for all HCWs to ensure adequate understanding of prevention guidelines 12. Limit work hours to <10 hours per shift 13. N95 masks reserved for HCWs performing intubations and other procedures generating aerosol. 3. Methodology Study design: Interrupted Time Series (Quasi-experimental Design). This study design is used to evaluate the impact of an intervention such as a policy change in real world settings. The outcomes are assessed repeatedly over time, both before and after the intervention is introduced (Shadish, Cook and Campbell, 2002). Study area: The study will be conducted in medical wards at Bugando Medical Centre (BMC). BMC is a tertiary teaching hospital that offers super specialized medical care to all specialties, in the city of Mwanza, Tanzania. It has a total bed capacity of 900, 154 of which are located in the medical ward. The medical department has 4 wards (both private and public patients) and 8 units. The medical staff compromises of 20 medical specialists who are allocated in different medical units within the department, 50 nurses and 40 medical ward attendants. Study population: All HCWs in the medical wards at BMC Study procedures: Using the WHO guidelines (WHO Global Infection Prevention and Control Network, 2020; World Health Organisation, 2020) for prevention of infection to HCWs from COVID 19, the first adapted in-hospital guideline to all medical HCWs at BMC will be deployed by a distinct medical committee after obtaining waivers from the BMC ethical board. Once approved, training will be done for all medical in-patient HCWs every day during the first week to ensure the protocol is well adopted and understood. Training will be conducted every morning from 730am in the usual departmental meetings before clinical routine work to 900am. Attendance and contact information for attendees will be captured. The training will also encompass knowledge on safety measures in handling a suspected or confirmed COVID 19 case. All in-patient medical HCWs will be assessed biweekly for infection with COVID 19 via phone interview (we will determine both suspected cases by verbal report and confirmed cases by PCR). Qualitative interviews will also be conducted either in-person or via phone, lasting ~15 minutes. This will be minimally structured, based on an interview guide, and implemented by the principal investigator to assess for knowledge, attitude and practices of HCWs to the adapted protocol. Interview guides will be composed in English, translated into Kiswahili, and back translated to ensure integrity of translation. Protocol adaptation: Following the assessment phase, we will decide whether the existing protocol can be applied to medical HCWs (""Decision"") based on the outcomes. If we decide that the protocol will not be useful, we will revise and adopt another protocol. Next, we will conduct another round of training to HCWs using the revised protocol and assess for study outcomes. We will review the outcomes and a draft of the adapted protocol will be submitted to the hospital management for review (""Production""). Based on hospital feedback, we will produce a final adapted BMC guideline for protecting medical in-patient HCWs from COVID-19 in Tanzania. 4. Approach used to maximize the impact of research outputs, to improve health and the research community Findings from this implementation study will provide the most optimal strategies to help HCWs protect themselves from COVID 19 in Tanzania. The adapted protocol will be shared with other hospital institutions to help prevent infections in resource limited settings. 5. Expected outcomes 1. Number of HCWs infected 2. Knowledge, attitude and practices of HCWs to the adapted protocol 6. My role in the project As an internal medicine physician, my role will be to actively participate in developing and revising the various versions of the adapted protocols until the final draft, train the medical staff in the process of adopting the protocol, and follow up with the HCWs via interviews. This study will be conducted in collaboration and mentor-ship from other senior faculty members experienced in doing implementation studies: Prof. Robert Peck (Head of Research Department of Internal Medicine) and Dr. Fredrick Kalokola (Head of Department Internal Medicine).",2021,2021,Catholic University of Health and Allied Sciences - Bugando Medical Center (CUHAS-BMC),6187.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Tanzania,Tanzania,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +C09639,20/087,Informational and structural barriers to uptake of preventive behaviours among Healthcare workers working in both isolation and non-isolation sitesduring COVID 19 in Zambia,"1) Project background, context and needs addressed Countries all over the world areimplementing different strategies to prepare for expected increase in numbers of patients who test positive for COVID-19.The rising number of positive COVID-19 cases puts healthcare workers(HCW) at increased risk of infection,posing a serious threat to the epidemic chain as healthcare workers are the frontliners helping in controlling the pandemic.(1) As the numbers of positive patients increase, the risk to Healthcare also increases, putting a strain on supply of Personal protective equipment (PPE) as shortages of PPE are being noted in most health facilities around the world.(2) Other factors that put healthcare workers at risk includedelayed recognition of COVID-19 symptoms and lack of experience in dealing with respiratory pathogens,exposure to large numbers of patients in long shifts with inadequate rest periodsand lack of measures to prevent the spread in hospitals.(3)Thus, the World Health Organisation WHO recommends training and support for HCWs including to recognize respiratory diseases occurring in hospital settings even as it attempts to ensure consistent supply and distrubition of PPE(3,7). Countries have systematically implemented various infection preventionand control measureswith good results - for example, using refined management theory,a general hospital in China ensured zero hospital-acquired COVID-19 infections among hospital staff.They formulated prevention and control measures and standards for non-isolation areas in the hospital,infrared temperature screenin was performed on all entering the hospital those with high fever were escorted to fever outpatient. They also ensured that rapid hand sanitizer stations were at all entrances. All outpatients were scheduled, to control patient flow and surfaced were wiped every 4 hours. For inpatient education material was placed in strategic areas with emphasis on hand hygiene, wearing masks correctly and reducing the number of visitors. Systematic training was also used to continuously give staff on the latest COVID-19 information(4) The Korean government ensured that HCWs received training in diagnostic testing for COVID-19, how to wear protective clothing, and in management of novel infectious diseases in screening clinics.(5) Singapore having learnt from the 2003 Severe Acute Respiratory syndrome (SARS) has begun to prepare for new pandemics by establishing a 330 bed facility and stockpiling PPE and barrier equipment. Other measures such as having strict staff management polices in place has also helped reduce infection. These include 14-day compulsory leave of absence for staff who traveled overseas, twice daily temperature screening for all clinical and nonclinical staff, separation of teams into those who care for COVID-19 patients and those who do not, and designated clean areas.(6)Staff with respiratory symptoms are also not allowed to come to work until symptoms completely resolve . In Italy, organizations such as Médecins Sans Frontières (MSF) helped separate wards that could be contaminated from wards less at risk and monitoring of patient and staff flow.They are also helping to increase knowledge of healthcare staff on how to protect themselves and better manage patients.(8) Zambia reported its first two confirmed COVID-19 cases on Wednesday, 18 March 2020.9 Of the76 confirmed COVID-19 as of 24 April 2020,15 are HCWs, of whom at least 5 were working in isolation wards.10This raises questions about the training, systems, and PPE available and used by HCWs to prevent and controlCOVID-19 infection among HCWs in both non-isolation and isolation facilities. Establishing what HCWs know, their perceived threat of COVID-19 and their ability to practice preventive behavioursdissagregated by those directly working with and those not working with COVID-19 patients is important to design interventions that help control the spread of infection among HCWs including and not limited to training, system changes, practice and policy. 2) Aims or research questions being addressed This exploratory research aims to gather HCWs'perspectives on their knowledge and skills needs, their attitudes towards, and their ability to practice preventive behaviorsin the context of COVID-19 in Zambia.This perspectives will help inform interventions that reduce the risk of COVID-19 transmission in health care settings.The research questions we hope to answer are as follows: 1. What information do healthcare workers need to better protect themselves and their patients from the risk ofacquiringCOVID-19? 2. How do HCWs feel handling patients who present with respiratory illness in the time of COVID-19? 3. What are the motivators, facilitators and barriers to the uptake ofinfection prevention practices to avoid contracting COVID-19? How do these differ between HCWs in both isolation and non-isolation facilities? 3) Study design This qualitative study will use in-depth interviews with 20 healthcare workers, 10 from the isolation centres and 10 from two health centres -- one in high and the other in low density hotspots in Lusaka, the epicenter for COVID-19 in Zambia.Ourstudy populations will includeMinistryOf Health Zambiastaff,in particular HCWsand support staff who are directly involved in triaging, screening, testing and caring for COVID-19 patients in isolation facilitesandnon-isolation sites. If the current guidelines of social distancing are still in place by the time the study starts, we will conduct In-depth interviews by phone, recruiting staff through the facility-in-charges and through the Zambia National Public Heath Institute (ZNPHI). The ZNPHI leads the national epidemic response. Staff will be contacted on phone numbersprovided by the in-charges and ZNPHI. The lead qualitative researcher (this applicant) will explain the study and emphasize voluntary participation, confidentiality and right to refuse/withdraw with no penalty. Those interested to proceed will be asked for verbal consent before the IDI. The IDIs will be conducted on a conference call to includea research assistant, who will document the conversation, engagement and emotion. The interview will be audio recordedwith participants' consent. Each interview is expected to take 1-1.5 hours and will be conducted in English.Which is predominantly spoken in Lusaka.Interviewswill then be transcribed verbatim.The computers used for data entry will be password-protected and have regularly updated anti-virus application. No personal identifiers will be noted; pseudonyms or codes will replace any identifying information arising during interviews. Asemi-structured IDI guide will be used to collect the data andwillcontain open-ended but key questionstofullyexploreparticipantexperiencesthroughthe normal flow of conversation and probes to gain deeper insight and to pursue new information. Questions will explore the Once the interviews are completed, with the participant present on phone or in-person, interviewers will review the field guide and check the availability of notes and audio recordings to ensure that nothing has been left out.The recordings will then be transcribed verbatim. Final transcripts will be reviewed for accuracy against original notes and recordings for at least two transcripts. Recorded data will be transferred on to a lockable pass-word protected computer. Once this process is done and the quality of transcripts has been assured, recordings will be destroyed. All electronic data will be stored in secure locations, with access permissions only for authorized users. At a minimum, data will be stored until the final analysis and reporting on the project are complete. Ethical Considerations Ethical approvals will be sought from University of Zambia Biomedical Research Ethics Committee (UNZABREC).Informed consent will be obtained from persons completing the interviews. Any participants showing signs of distress will be referred to appropriate care. 4) Approach used to maximise the impact of research outputs, to improve health and the research community The findings from this study will be disseminated to relevant stakeholders such as the Ministry of Health, Zambia National Public Health Institute's Epidemic Preparednessand Response team, who are mandated to ensure that national policies, plans, procedures and protocols for public health emergency preparedness and response conform with the International Health Regulations.(11)Organisations like the National Health Research Authority (NHRA) are also key stake holders, part of whose mandate is dissemination research in Zambi and knowledge translation.(12) We will aim to share our findings with Philantrophic organizations such as the Jack Ma foundation who are distributing medical supplies around the world to the most affected parts.(13) We plan to publish the findings in relevant journals and contribute to the knowledge currently being generated on prevention of COVID-19 in healthcare settings with implications for other sub-Saharan African countries. 5) Expected outcomes We hope the findings from this study can be discussed with the relevant stakeholders who can tailor training, health policy and procedures to refineemergency response toolkits or practices for HCWs to use during pandemics.The results from this study will complement current initiatives by providing recommendations on how best HCWs can reduce the risk of contracting COVID-19 in both isolation and non- isolation facilities and for future emergencies.Our rigorous qualitative method design will provide robust evidence needed to protect our frontline workers and keep pace with the dynamic COVID-19 situation in Zambia. 6) Your role in the project I will lead the project and with a research assistant, will collect, analysis and report findings.   References 1. https://www.journalofhospitalinfection.com/article/S0195-6701(20)30187-0/fulltext#secsectitle0025 2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30644-9/fulltext 3. https://www.weforum.org/agenda/2020/04/10-april-who-briefing-health-workers-covid-19-ppe-training/ 4.https://www.sciencedirect.com/science/article/pii/S2352013220300533?via%3Dihub 5. https://www.jeehp.org/upload/jeehp-17-10.pdf 6. Feng Tan L, Preventing the Transmission of COVID-19 Amongst Healthcare Workers, Journal of Hospital Infection, https://doi.org/10.1016/j.jhin.2020.04.008. 7. https://www.who.int/news-room/detail/03-03-2020-shortage-of-personal-protective-equipment-endangering-health-workers-worldwide 8. https://www.msf.org/protecting-hospital-staff-coronavirus-covid-19-codogno-italy 9. Ministry of Health Zambia. https://www.facebook.com/mohzambia/ COVID-19 UPDATE #1 SUMMARY. 2020; 10. https://diggers.news/local/2020/04/22/zambias-covid-19-cases-surge-to-70/ 11. http://znphi.co.zm/preparedness-and-response.html 12. https://www.nhra.org.zm/ 13. https://www.jackmafoundation.org.cn/our-work/#field-medical",2021,2021,Centre for infectious disease research in Zambia (CIDRZ),6700,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Zambia,Zambia,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +C09640,20/092,"Risk Communication and Community Engagement Strategies, Surveillance Systems and Laboratory Testing Capacity for COVID-19: A Comparison of 13 WHO-Prioritized African Countries","1. Project background, context and needs addressed The Director-General of the World Health Organization (WHO) declared the novel coronavirus outbreak (also called COVID-19, or 2019-nCoV, or SARS-CoV-2) as pandemic on 11 March 2020, after it was previously declared a global health emergency. African countries are not spared from the threat and the impact of this pandemic on global health security, which currently seems to have originated from China. The WHO has prioritized 13 African countries (Algeria, Angola, Côte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Kenya, Mauritius, Nigeria, South Africa, Tanzania, Uganda, and Zambia) due to their direct links or high volume of travel to and from China. These countries were warned to be more vigilant to ensure effective containment of COVID-19. In response, these 13 countries have set up measures to respond to COVID-19 pandemic. Their efforts have not been without challenges, such as weak healthcare systems and double burden of communicable and non-communicable diseases among others. In 2019, the Johns Hopkins Center for Health Security reported the African continent as least prepared to respond to health emergencies, treat the sick and protect health care workers. The weak healthcare systems and high prevalence of malnutrition, malaria, HIV/AIDS, and tuberculosis are further challenges facing the continent. Thus, this global pandemic serves to create unique challenges that will test the emergency responsiveness of health systems in these countries. This calls for the need for this study. We would like to compare the public health responses to COVID-19, across the 13-WHO-prioritized African countries, focusing on risk communication and community engagement strategies, surveillance systems and laboratory testing capacity. In addition, we will derive lessons from their responses for future public health decision and policy making and epidemic preparedness. 2. Aim of the research project The project aims to compare public health responses to the COVID-19 pandemic, with a focus on risk communication and community engagement strategies, surveillance systems and laboratory testing capacity across the 13 WHO-prioritized African countries. Specifically, we would like to: a. Describe pre-existing physical infrastructure, equipment, and health policies relating to pandemics present in these countries prior to the COVID-19 pandemic b. Enumerate the initial strategies deployed for COVID-19 risk communication and community engagement, surveillance and laboratory testing across the WHO-prioritized African countries. c. Identify and describe the challenges encountered in the implementation of the aforementioned strategies from a health systems perspective. d. Catalogue how each country has circumvented the unique challenges they have faced in implementing the aforementioned strategies.   3. Study Design This is a descriptive study aimed at comparing public health responses to the COVID-19 pandemic among the 13 WHO-Prioritized African countries, focusing on risk communication and community engagement strategies, surveillance systems and laboratory testing capacity. The 13 WHO-prioritized African countries are: (in alphabetical order) 1. Algeria 2. Angola 3. Côte d'Ivoire 4. Democratic Republic of the Congo 5. Ethiopia 6. Ghana 7. Kenya 8. Mauritius 9. Nigeria 10. South Africa 11. Tanzania 12. Uganda 13. Zambia A questionnaire shall be developed to cover the domains to be examined in this study. These domains are: -Risk communication strategies -Community engagement strategies -Surveillance systems -Laboratory testing capacity In order to create this questionnaire, a systematic literature review for parameters to be included in each of the above domains will be conducted. The systematic literature review will be conducted using online databases, including PubMed, Medline, Google Scholar, The Cochrane Library, Popline, Web of Science, Science Direct and WHO Library Database. Search terms and strategy will be agreed upon by the team and will be documented. The questionnaire shall then collate the parameters pulled from the systematic literature review and shall be designed for use by the study team. The parameters will be examined in the following subdivisions: 1. Pre-existing infrastructure, equipment, personnel, and health policies relating to pandemic response present in these countries prior to the COVID-19 pandemic. 2. Initial strategies relating to infrastructure, equipment, personnel and health policies deployed as response to COVID-19. 3. The variety, difficulty and sectoral involvement of the challenges encountered in the implementation of the initial strategies 4. Solutions to the challenges faced in implementing the initial strategies It will be placed online through Google Forms, selected for its time stamp feature, ease of access across different countries, and low internet bandwidth requirement which is ideal for settings where the internet is not accessible or difficult to access. This questionnaire shall be validated through experts in global and public health, health policy, and methodological research. It will be piloted in Nigeria by 2 independent researchers and compared for consistency. Nigeria was selected as the pilot country due to the proximity of the researcher to this country. Responses to the questionnaire shall be collated through examination of a variety of sources, including: -Government websites of each respective country -Publicly available documents in the health ministries of each country -Broadcast media -Social media -Online databases: PubMed, Medline, Google Scholar, The Cochrane Library, Popline, Web of Science, Science Direct and WHO Library Database The sources of the responses to the questionnaire shall be documented and referenced clearly. These sources shall be supplemented by individual online interviews with key individuals from each of the 13 countries. These individuals shall be selected based on their involvement in public health, health policy, and government response to COVID-19, such as membership in their national COVID-19 task force, local public health body, or local centre for disease control. A minimum of 2 individuals per country shall be interviewed. The consent of the interviewees shall be procured and their responses shall be anonymized in the final research output should the interviewees request this. Meetings shall be set-up online due to the social distancing restrictions in place to COVID-19 and will involve 2 interviewers. These meetings shall use the questionnaire as a discussion guide, although interviewers will be permitted to ask probing questions to further elucidate information from unclear responses. In addition, the initial responses to the questions as taken from the online review shall be validated during each interview. The meetings will be transcribed, with results documented using Google documents. After each meeting, interviewers will triangulate findings with each other and document the agreed responses in the questionnaire response form. Once all data has been collected, the researchers shall collate responses into the previously stated domains, parameters, and subdivisions per country. Tabulation of these responses to summarize findings across countries shall likewise be performed. 4. Approach used to maximize the impact of research outputs, to improve health and the research community -The findings of the study will be published in a reputable public health journal. -A focused group discussion shall be formed with the interviewees from each country to present the findings of the study. Plans for larger engagement shall utilize Global Health Focus and its network, which includes trainees and graduates of different health professions, as well as academics and policy makers from Asia-Pacific, Africa, Europe and North America. Efforts shall be made to coordinate with the Africa Centres for Diseases Control, WHO African Region Office and other non-government and civil society organizations for public health decision, policy making and in preparation towards possible future pandemic. -Policy and infrastructure suggestions shall be collated and re-disseminated in a subsequent paper. -For public engagement, findings from the study will also be shared through blogs and news outlets. Due credit will be given to Royal Society of Tropical Medicine and Hygiene for the funding support in all publications. 5. Expected outcomes With this study, we hope to expand knowledge base, identify research gaps and provide clear understanding of public health responses concerning risk communication and community engagement strategies, surveillance systems and laboratory testing capacity for effective containment of COVID-19 in the WHO-prioritized countries. It will also provide the opportunity for other African countries to learn from the WHO-prioritized countries which strategies are likely to work given the unique challenges. In addition, findings from this study have potential impact for future public health preparedness and policy making towards pandemic and other outbreaks including other diseases afflicting the region. 6. Your role in the project As principal investigator, I will be in charge of managing the methodology of the study and will be allocating resources across the study group. I will lead the communication of the study participants, and function as one of the literature reviewers and interviewers in the study. I will likewise resolve any potential conflicts and issues that arise when it comes to study implementation. 7. Project Supervisor Adrian Paul J. Rabe, MSc, MD, FRSPH, Managing Director, Global Health Focus",2021,2021,Global Health Focus,6200,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Algeria | Angola | Cote d'Ivoire | Congo (DRC) | Ethiopia | Ghana | Kenya | Mauritius | Nigeria | South Africa | Tanzania | Uganda | Zambia,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Community engagement | Communication,2020 +C09641,20/095,"Knowledge and Preventive Practices towards COVID-19 among staff and students in the Walter Sisulu University, South Africa; a mixed method study","1) Project background, context and needs addressed As the new decade began in 2020, there was also a global increase in infection and death from a deadly invisible virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) originating in Wuhan, Hubei Province, China. (1-5) [1-5]. Today, more than 200 countries worldwide are affected by this disease (COVID-19), a fatality rate of 6.87% [6]. Africa accounted for approximately 20.313 (0.84%). Africa had the most reported cases in the Africa continent, 3,158 (15.56%), followed by Egypt 3,144 (15.48%) on 20 April 2020[6, 7]. Africa was a major concern throughout the area. Evidences suggest that human to human transmission is caused as the main symptoms within one week of viral infection by droplets from coughing or snoring or direct contact with contaminated surfaces that may cause tough or / fever or/ or sore throat [4]. Countries worldwide have taken a broad array of steps to avoid the transmission chain of this viruses, and to reduce its harmful impact [8] in response to this deadly global COVID-19 pandemic. One such initiative is the promotion of a high standard of hygiene (e.g., daily soap hand washing), temporary closing of educational facilities, libraries, theatres, shopping mores, dining places, and avoiding religious activities and public meetings, which involves non- pharmaceutical interventions (NPIs). As vaccines and effective therapies are currently not in place for the disease, these steps have been introduced with a view to planning essential services such as high demand medical care [10]. The global trend and magnitude of this pandemic have unmistakably led many African countries, including South Africa, to enforce the postponement and closure of the academic activities of the educational institution in an effort to prevent transmission of the virus [11]. For this reason, the African education sector is now faced with a reduction in funding for advanced innovative research, along with fewer face-to-face conferences and collaborations [12]. Another effect of this pandemic is online education, currently seen as an alternative means of continuing education and its economic impact [13]. As the global fight against COVID-19 continues and plans for alternative forms of learning are being developed, the adherence of students and university faculties to current preventive measures, such as hand washing and social distancing, is crucial. This is because knowledge, attitudes and preventive practices (KAP) towards COVID-19 also play a critical role in this fight [14]. As a result, this study is designed to provide evidence from the assessment of COVID-19 Knowledge, Attitudes and Preventive Practices by staff and students at Walter Sisulu University (WSU), Eastern Cape, South Africa. 2) Aims or research questions being addressed Specific Aim 1: To understand if the staff and students have adequately accurate knowledge about COVID-19 and preventive measures Specific Aim 2: To describe the attitude toward COVID-19 by students and faculties in the Walter Sisulu University, South Africa. Specific Aim 3: To assess the preventive practices toward COVID-19 by students and faculties in the Walter Sisulu University, South Africa. 3) Study design Study design This study would apply a concurrent mixed-method study design involving both quantitative (short online survey for staff and students) and qualitative (KITIs for selected respondents in the institution). Study setting and sampling This study will be conducted in the Eastern Cape (EC) province of South Africa, with an estimated population of 6 712 276 (11.4% of the total population of South Africa in 2019) [17]. There are more than eight (8) higher public institutions in the Eastern Cape, including Walter Sisulu [18]. Walter Sisulu University was established on 1 July 2005 as a result of a merger between Border Technikon, Eastern Cape Technikon and the University of Transkei. The university is named after Walter Sisulu, a prominent figure in the struggle against apartheid and has four campuses, namely Mthatha, East London (Buffalo City), Butterworth and Komani (Queenstown). At present, the university has more than 31,500 students enrolled in various faculties for various academic degrees such as diplomas, bachelor's degrees, honors, master's degrees and doctoral degrees across campuses [19]. 4) Approach used to maximise the impact of research outputs, to improve health and the research community Quantitative approach A short online survey will be used to assess awareness and preventive practices towards COVID-19 among staff and students at Walter Sisulu University. Study Population and sample size: All consenting staff and students in the WSU will be eligible to study. Using Stata statistical software, the minimum sample size of students to be included in this study will be approximately 800 using Stata: since no previous study was available in South Africa, we assumed a 50% knowledge on COVID-19 by students of WSU, effect size of 5% difference, power of 80%, level of significance set at 0.05. Conversely, assuming a 50% knowledge on COVID-19 by staff of WSU, effect size of 20% difference, power of 80%, and level of significance set at 0.05, approximately 320 staff would be enrolled in the study. Data collection: After a preliminary review of the questionnaires that will be adopted, the data will be retrieved using secured online self-administered short questionnaires. Data collection will be done by the study participants who will be sent a link to complete the online survey questionnaire. Measures: Variables to be collected will include sociodemographic variables of study participants (age, sex or gender, occupation, educational status, faculty, department), awareness variables and preventive practices for COVID-19 by staff and students. View the demo online short questionnaire here - https://forms.gle/HVoSYDdvLfevzqsV7. Data management and analysis: Data will be entered into Epidata software and Stata 14.1 will be used for the analysis. Descriptive and inferential analysis will be carried out, where appropriate, with a statistical significance level of 0.05. Qualitative approach A qualitative research method will be conducted to explore knowledge, attitudes and preventive practices towards COVID-19 among purposively selected staff and students. Data collection, management and analysis: Approximately twenty-five key informant telephonic interviews (KITIs) will be conducted among selected students and WSU staff, respectively. Interview questions for the KITIs will be finalized. Interviews will be recorded, and notes will be taken as well. In addition, the recordings would be transcribed and encoded into themes using both content analysis and grounded theory techniques [20, 21]. View the demo interview questions here - https://forms.gle/KBsKqMJ1f5yv46PEA. Ethical considerations This proposal will be submitted to the Faculty of Health Sciences Research and Ethics Committee for ethical approval, along with the completed Ethics Application Form. Data would be anonymized in accordance with the ethical principles for protecting the information of study participants. All completed data will only be made available to appropriate study personnel and stored in locked cabinets at Walter Sisulu University. 5) Expected outcomes I expect the study to produce manuscript publications and abstract for conference presentation. I am also optimistic that the findings will also provide additional pilot data to develop another grant application that will focus on developing interventions that would facilitate high-level preparedness for future emerging diseases. In addition, the process of conducting this study would enhance my expertise and skills in formulating, designing health interventions and conducting multi-disciplinary and international research projects. 6) Your role in the project - I would be an investigator.",2021,2021,Walter Sisulu University,4644,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C09642,20/105,NASAL CARRIAGE OF VIRULENT STAPHYLOCOCCUS AUREUS: A POSSIBLE CO-MORBIDITY OF COVID-19,"BACKGROUND Coronavirus diseases-19 (COVID-19), caused by a coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a respiratory disease. The disease was first reported in China in December 2019, and has currently spread to most part of the world resulting to a global pandemic. There are currently no vaccine and specific antiviral drug recommended for COVID-19 treatment; however, the disease can be successfully managed by treating specific symptoms such as the use of fluids to reduce dehydration risk, medication to reduce fever, and oxygen therapy for respiratory failure [1,2]. Most people with this disease exhibit mild to moderate symptoms and fully recover without special medications; however, elderly people and people with other co-morbidities like cardiovascular diseases, asthma, diabetes, chronic respiratory disease, and the immunocompromised develop more severe illness leading to fatality [1-3]. Though these conditions are the most commonly reported conditions influencing COVID-19 severity, bacterial superinfection may also affect the severity of disease. In the SARS-CoV epidemic of 2003, an increased rate of methicillin-resistant Staphylococcus aureus (MRSA) was reported from the pre-SARS to the SARS period [2]. In the current COVID-19 pandemic, a case-fatality of a French man in his thirties with no underlying medical conditions has been reported [4]. Investigations into the cause of the severe symptoms seen in this patient showed the presence of a cytotoxin producing methicillin-susceptible Staphylococcus aureus which was inducing necrotizing pneumonia in the patient, leading to his death [4]. Considering the similarities already reported between the 2003 coronavirus infection and this SARS-CoV-2 infection [5], there is a need to assess the presence of Staphylococcus aureus in COVID-19 patients, and its treatment be considered to reduce risk of superinfection and ultimately the severity of disease in patients with COVID-19. AIMS Staphylococcus aureus is a human commensal that causes community-acquired and nosocomial infection. The increase in the resistance of this bacterium to antibiotics makes it of great clinical importance. Nasal carriage of S. aureus are reported to increase the risk of acquiring both community and hospital-acquired infections, and are particularly implicated in bronchopulmonary infection, causing both upper and lower respiratory tract infection [6, 7]. The prevalence of nasal carriage of staphylococcus is high in Nigeria even in apparently healthy people [8-9]. There is currently a paucity of data on the different comorbidities that might vary in different populations with COVID-19. Hence, the aim of this study is to evaluate the association of nasal carriage of S. aureus and its association with COVID-19. The objectives of this study are: 1. To determine the nasal carriage rate of S. aureus among suspected patients presented for SARS-CoV-2 screening 2. To evaluate antibiotics resistance patterns in the identified S. aureus strains. 3. To examine the association between nasal S. aureus carriage and SARS-COV-2 infection. 4. To assess the prevalence and distribution of antibiotic resistance and virulence genes among the S. aureus strains. 5. To type isolates into the different S. aureus protein A types STUDY DESIGN The study will be a quantitative study using a cross-sectional research design. The target population for this study will include individuals who present for SARS-CoV-2 testing at the Nigerian Institute of Medical Research drive through COVID-19 testing centre. The inclusion criterion for this target population is that they are willing to participate in the study. The sample size for this study was estimated using the formula for single proportion. With Z set at p<0.05 = 1.96, d at 0.05, and the expected proportion in the population based on a previous studies was set at 57% [9]. The estimated sample size was 380 based on this calculation. Convenience sampling will be used to recruit participants into the study. The two anterior nares of the participant will be swabbed using a sterile swab moistened with normal saline following all safety guidelines. The samples will immediately be plated on mannitol salt agar and nutrient agar and incubated within two hours of collection at 37ºC for 18 - 24 hours. The swab stick will also be transferred into a lysis buffer containing guanidine isothiocyanate for viral inactivation and transported to the laboratory for direct molecular detection of S. aureus. Isolates will be identified using colony morphology, gram staining, slide agglutination and tube coagulase test, and molecular amplification of the 16s rRNA gene specific to S. aureus. Pure isolates will be subjected to antimicrobial susceptibility testing using the disk diffusion method as recommended by Kirby-Bauer method according to the Clinical and Laboratory Standard Institute (CLSI) criteria with the following antibiotics: Gentamicin (10µg), Augmentin (30µg), Streptomycin (10µg), Tetracycline (10µg), Cotrimoxazole (25µg), Cloxacillin (5µg), Chloramphenicol (10µg), Erythromycin (5µg), Imipenem (10µg), Cefuroxime (30µg), Amoxycillin (10µg), Rifampicin (5µg), Cefoxitin (30µg), Methicillin (5µg), ciprofloxacin (5 μg), Ofloxacin (5µg), ceftriaxone (30μg) ceftazidime (30μg), vancomycin (30µg) and azithromycin (15µg). Sensitivity will be read after 24 hours incubation at 35º-37º C. Isolates will be regarded as sensitive or resistant according to the CLSI criteria [10]. DNA will be isolated from all identified isolates and directly from the swab samples using a commercial DNA extraction kit. The mecA and the SCCmec typing will be done using a multiplex polymerase chain reaction (multiplex PCR) method as previously described [11]. The panton valentine leucocidin (pvl) toxin has been associated with necrotizing pneumonia in children [12, 13]. The virulence of the S. aureus will be evaluated with regards to pvl using PCR methods as previously described [13]. The isolates will also be typed into the different S. aureus protein A (spa) types using methods as previously described [14]. Statistical analysis will be done using SPSS version 20.0. Chi square analysis will be carried out to determine if there is a significant association between the presence of S. aureus and SARS-CoV-2 detection and also if there is an association between the presence of virulent S. aureus strains and COVID-19 severity. Ethical considerations Ethical approval will be obtained from the Institutional Review Board of the Nigerian Institute of Medical Research. Apart from the nasal swabs, demographic information such as age and gender of the participants will be collected. Though no identifying information will be collected from the participants, the result of the COVID-19 screening and severity of the diseases in the participant will also be required. MAXIMISING THE IMPACT OF RESEARCH OUTPUTS Collaborations will be made with relevant experts to improve the research output of this project. This will involve collaborating with laboratory technicians, microbiologists and virologists involved in COVID-19 research. The result of this study will be sent to the head of the Nigerian Institute of Medical Research so as to influence health policies by the federal ministry of health. Additionally, the result of this study will be published in open access, peer-reviewed journals, and will also be presented in local and international conferences EXPECTED OUTCOMES Considering the increase in the incidence of COVID-19 in Nigeria, the fact that Nigeria already has a high prevalence of nasal carriage of S. aureus even in apparently healthy people, it is expected that the nasal carriage of virulent S. aureus may influence the severity of COVID-19. The result of this study may help highlight the need to assess the presence of nasal carriage of S. aureus as comorbidity in COVID-19 patients, and consider the treatment of S. aureus co-infection in COVID-19 patients as a means to reduce the severity of disease in COVID-19 patients. ROLE IN PROJECT - Principal Investigator Some Selected References 1.. Lupia T, Scabini S, Pinna SM, Di Perri G, De Rosa FG, Corcione S. 2019 novel coronavirus (2019-nCoV) outbreak: A new challenge. JGAR. 2020 Jun; 21:22 2. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb; 323(13):1239 3. World Health Organization. Coronavirus [Internet]. WHO; 2020 [Cited April 19, 2020]. Available from https://www.who.int/health-topics/coronavirus#tab=tab_1 4. Duployez C, Le Guern R, Tinez C, Lejeune A-L, Robriquet L, Six S, et al. Panton-Valentine leukocidin-secreting Staphylococcus aureus pneumonia complicating COVID-19. Emerg Infect Dis. 2020 Aug; 26(8). 5. Ceccarelli M, Berretta M, Venanzi Rullo E, Nunnari G, Cacopardo B. Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet? Eur Rev Med Pharmacol Sci. 2020 Mar; 24(5):2781 6. Watanabe H, Masaki H, Asoh N, Watanabe K, Oishi K, Kobayashi S, et al. 2000. Molecular analysis of methicillin-resistant Staphylococcus aureus as a causative agent of bronchopulmonary infection: relation to colonization in the upper respiratory tract. J. Clin. Microbiol. 2000 Oct; 38(10):3867 7. Corne P, Marchandin H, Jonquet O, Campos J, Bañuls AL. Molecular evidence that nasal carriage of Staphylococcus aureus plays a role in respiratory tract infections of critically ill patients. J Clin Microbiol. 2005 Jul; 43(7):3491 8. Tuta KE, Okesola AO, Umeokonkwo CD. The Prevalence and Risk Factors Associated with Nasal Methicillin-Resistant Staphylococcus Aureus Colonization among Children in a Tertiary Hospital in Nigeria. Ethiop J Health Sci. 2019 Jul; 29(4):487",2021,2021,NIGERIAN INSTITUTE OF MEDICAL RESEARCH,6566,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,Clinical characterisation and management,Disease pathogenesis,2020 +C09662,221571/Z/20/Z,POETIC-COVID: Provision Of Essential Treatment In Critical Illness in COVID-19,"Conventional evaluation of new medicines is not fast enough for a pandemic. Our aim is to accelerate this process, rapidly identifying which drugs are safe and potentially effective treatments for COVID-19. AGILE is an innovative, multi-arm, multi-dose, multi-stage Phase I/IIa Bayesian adaptive platform protocol to evaluate experimental COVID-19 therapies, and to funnel plausible candidates into large Phase IIb/III trials such as RECOVERY and SOLIDARITY. We will efficiently eliminate candidates with little or no prospect of clinical success. AGILE will recruit COVID-19 patients into very early phase clinical studies, including first-in-human. The innovative design allows us to move seamlessly from first-in-human use to finding the optimal dose for COVID-19 patients. The trial is pragmatic (requiring only small numbers of patients), adaptive (so that the right drug is tested in the right group of COVID-19 patients, either in the community or in hospital) and statistically efficient (so that several drugs can be tested in parallel, making best use of a small number of patients). Our primary focus is population-scalable antiviral drugs for early treatment of COVID-19, for which we will recruit primarily in the community. AGILE has full regulatory and ethics approvals in the UK",2020,2022,London School of Hygiene & Tropical Medicine,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Malawi | Tanzania,"Therapeutics research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2020 +C09663,221590/Z/20/Z,AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment,"Conventional evaluation of new medicines is not fast enough for a pandemic. Our aim is to accelerate this process, rapidly identifying which drugs are safe and potentially effective treatments for COVID-19. AGILE is an innovative, multi-arm, multi-dose, multi-stage Phase I/IIa Bayesian adaptive platform protocol to evaluate experimental COVID-19 therapies, and to funnel plausible candidates into large Phase IIb/III trials such as RECOVERY and SOLIDARITY. We will efficiently eliminate candidates with little or no prospect of clinical success. AGILE will recruit COVID-19 patients into very early phase clinical studies, including first-in-human. The innovative design allows us to move seamlessly from first-in-human use to finding the optimal dose for COVID-19 patients. The trial is pragmatic (requiring only small numbers of patients), adaptive (so that the right drug is tested in the right group of COVID-19 patients, either in the community or in hospital) and statistically efficient (so that several drugs can be tested in parallel, making best use of a small number of patients). Our primary focus is population-scalable antiviral drugs for early treatment of COVID-19, for which we will recruit primarily in the community. AGILE has full regulatory and ethics approvals in the UK",2020,2023,University of Liverpool,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation | Wellcome Trust,United Kingdom | United States of America,Americas | Europe,Europe,Africa | Europe,,,,United Kingdom,United Kingdom | South Africa | Uganda,"Therapeutics research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2020 +C09664,222406/Z/21/Z,RECOVERY (Randomised Evaluation of COVID-19 Therapy) International,"The Phase 3 RECOVERY platform has been a success, recruiting over 13,500 patients and producing 3 clear, world practice-changing results in the first 100 days of recruitment. The RECOVERY team has been approached by clinical investigators from various LMICs who wish to participate in RECOVERY. As it becomes clear that this pandemic will continue at various locations and paces over the next 24 months, there is an opportunity to increase the impact of the RECOVERY trial by expanding internationally. Expansion has the potential to speed up the assessment of novel treatments, increase the global relevance of the trial results, build capacity, and reduce wasted efforts on small uninformative studies. The key goal is to establish RECOVERY internationally, initially in Indonesia, Nepal and Vietnam, with a view to opening sites also in Africa.",2020,2022,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation | Wellcome Trust,United Kingdom | United States of America,Americas | Europe,Europe,South-East Asia | Western Pacific,,,,United Kingdom,Nepal | Viet Nam | Indonesia,"Therapeutics research, development and implementation",Therapeutic trial design,2020 +C09665,221495/Z/20/Z,Using action learning methodologies to examine responses to supporting people with complex needs during Covid-19 and implications for future practice,"There is a growing recognition within public and third sector organisations that outcomes-based commissioning and management ignores the complexity (at an individual, organisational and systems level) in which services operate. Some in the sector are experimenting with more developmental, collaborative, place-based approaches. However strategic development has recently been disrupted by Covid-19, which has forced services to change overnight whilst increasing support needs within communities. This project will analyse the ways in which community organisations have evolved during the crisis, and identify implications for future practice, not only in terms of service delivery models but also change processes and evaluation methods. CoLab is a cross-sector 'wellbeing hub' hosting 30 organisations from community, social enterprise and public sectors supporting people with complex needs (e.g. homelessness, mental ill-health). As an embedded researcher I will work with staff and users as co-researchers, drawing on research tools from different methodological approaches (e.g. participatory action research, ethnography, developmental evaluation) to explore their experiences of using, delivering and adapting services in a rapidly changing context. Key goals include producing recommendations for service development, identifying appropriate research methods to sustain an 'action research' culture moving forward, and sharing learning more widely within the sector and related academic fields.",2020,2021,University of Exeter,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C09666,221989/Z/20/Z,SARS-CoV-2 immunoepidemiology in Wellcome-funded urban and rural cohorts in Malawi : generating evidence to inform regional medium and long term decision making,"General population serosurveillance in low-income Africa is fundamental to understanding the population exposure to SARS-CoV-2, to explain the observed epidemiology and to ensure that ongoing control measures in the region are proportionate and are not guided by observations from very different settings. Detailed longitudinal immunological studies of infected individuals will be key to determining the long-term strategy in managing COVID-19 in highly vulnerable African populations. Utilising the longitudinal urban and rural cohorts established by the Malawi Epidemiology and Intervention Research Unit, and supported by international and national expertise, we will undertake population immunoepidemiological surveillance to understand the trends in exposure and transmission of SARS-CoV-2, risk factors for SARS-CoV-2 infection and severe disease, as well as the proportion of asymptomatic or pauci-symptomatic infection in the population to enable an accurate estimate of infection fatality rate. Furthermore, we will recruit individuals with evidence of past SARS-CoV-2 infection to a nested cohort with 3-monthly sampling, to explore the magnitude and duration of antibody response and protective immunity in the Malawian population, and at the same time creating a biorepository for further in-depth virological and immunological studies.",2020,2022,University of Glasgow,,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Africa,,,,Malawi,Malawi,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2020 +C09667,222574/Z/21/Z,National COVID Testing Africa AAPs/Centre,"To provide consistent technical support to national testing programmes for SARS-CoV-2 in Kenya, Malawi and South Africa. To support epidemiological research, clinical trials, immunological studies and genomics work To consolidate and maintain positive relationships with national policy makers. Our respective Wellcome AAPs/Centre (i.e. MLW, KEMRI-Wellcome, AHRI and CIDRI-Africa) have responded to the COVID-19 pandemic by making resources and staff available for SARS-CoV-2 testing, accounting currently for significant proportions of the local and/or national testing capacities, especially during surges. It is ethically imperative to provide national support alongside research-driven testing, and we have found this testing provided an opportunity to develop stronger relationships with national Government, with the potential for research that is better aligned to informing policy and with a better position to communicate. The immediate need has been covered by re-allocating resources for paused activities. The proposal here will bridge the gap between our immediate response and more sustainable long-term funding. This will allow us to sustain the enhanced relationships developed through our response to the pandemic, and will avoid the reputational risks that might be associated with failing to support the obvious ongoing need while establishing more sustainable long-term projects and core provisions.",2021,2022,University of Oxford,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Africa,,,,United Kingdom,South Africa | Malawi | Kenya,,,2021 +C09668,222112/Z/20/Z,Incentivising pharmaceutical companies to improve equitable access to healthcare interventions,"Equitable access is critical for maximising the impact of innovation and heavily depends on proactive actions by pharmaceutical companies, during and after the COVID-19 pandemic. In order to bring the pandemic to an end, achieve universal health coverage and protect the gains made on Sustainable Development Goal 3, the pharmaceutical industry will need to ensure that all scientific advancements benefit the maximum number of people, independent of the place they live or their ability to pay. The Access to Medicine Foundation (ATMF) has incentivised pharmaceutical company action to improve access to new innovations for more than a decade. By rewarding positive action, sharing best practices, and highlighting opportunities for change, the ATMF encourages companies to become willing partners to improve global access to their products. The ATMF will support Wellcome Trust's approach to equitable access to healthcare interventions through a combination of research and policy initiatives that will (a) incentivise pharmaceutical company action on COVID-19, (b) support global efforts to mainstream access principles during product development and (c) untap the potential of generic medicine manufacturers in expanding access to innovations in low- and middle-income countries. The request from the ATMF is for €471,750 (£425,000) from October 2020 to September 2021.",2020,2021,Access to Medicines Foundation (AMF),,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Netherlands,,Research to inform ethical issues | Health Systems Research,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Health service delivery",2020 +C09669,222305/Z/21/Z,Defining the Protective Immune Response to SARS-CoV-2 Using a Human Challenge Model,"Understanding the nature, effectiveness and durability of the human immune response to SARS CoV2 is crucial for vaccine development and effective public health management. We are beginning to understand the pattern and kinetics of the humoral response to natural infection but are less certain about other aspects of the response. We are unable to establish with certainty whether an individual with a particular titre of antibody, or a particular T cell response, is likely to be protected from reinfection and, if so, for how long. These are central questions for the development of an effective vaccine. A controlled human infection model will provide a more detailed understanding of the protective immune response. It will provide the opportunity to interrogate the full extent of the immune response at the time of exposure and will also allow the evaluation of the durability of immune responses of all kinds and how they correlate with protection. Key goals: To establish an MHRA-approved SARS CoV2 viral stock for use in a controlled human infection model To determine a challenge dose which is safe and allows virus to be recoverable from infected subjects",2020,2022,University of Oxford,,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2021 +C09705,315472,"Co-Duties: Democratic Commitments, Common Challenges, and the Common Good after COVID-19","This project will help us to better understand the relationship between individual duties and collective action in response to large-scale societal challenges. Grounded in a comparative (empirical and theoretical) study of the duties allocated to and undertaken by individuals during the COVID-19 lockdowns in Norway, France and the UK, the project analyses how duties were performed and understood during the time-limited period of the lockdowns. To do this the project combines innovative empirical investigation with comparative analysis and theory-building. In each country we study three basic duty types - (vertical) civic duties, (horizontal) duties of humanitarian assistance, and (closed) associational duties to family and neighbourhoods - to explore what it is that accounts for individuals' willingness to bear imperfect duties (duties of justice) beyond those they are required to perform by law (duties of justice). The study of duties has to date been substantially under-examined relative to the study of rights. CO-DUTIES innovates by first explaining this ""duties gap"", diagnosing its significance for political discourse (with respect to ""duties of virtue"" in particular) and then closing it through empirical research. Second, in a social science literature that mostly looks to rational accounts of self-interest and incentives to understand individual willingness to address ""greater good"" challenges, CO-DUTIES will apply the aforementioned insights into duty-bearing to frame a different way of approaching collective action problems. Finally, it develops a novel theoretical framework of ""duties regimes"" to this end. The project thereby provides new academic insights and policy-relevant knowledge: (a) through its theoretical contributions to history, political science and sociology, (b) as part of the broader societal learning from COVID-19, and (c) for our understanding of how best to respond to other ""greater good"" challenges.",2021,2024,Nasjonale samfunnsvitenskapelige institutter,1392000,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway | France | United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C09706,301929,Norways public-private cooperation for pandemic preparedness and response (PANPREP),"For Norway's public authorities, a serious pandemic is a question of when, not if. Consequently, Norway is currently investing significantly in pandemic preparedness - building up the capacity to detect and respond to pandemic threats and secure the resilience of critical infrastructure and society. To do so, the government increasingly depends on effective collaboration with global multi-stakeholder platforms (like the World Health Organization and the World Economic Forum) and a range of non-state actors, including both Norwegian and foreign non-governmental organizations (NGOs) and private corporations. These introduce innovative digital and biomedical technologies into preparedness work, but also infuse it with a new ethos and pose challenges relating to regulation and trust. PANPREP is the first social scientific project to examine these new constellations and their consequences for Norway's pandemic preparedness efforts. The aim of the project is two-fold: First, to examine how these new forms of inter-sectoral public-private collaboration resulting from growing reliance on private digital technologies, data and innovation in preparedness work, operate in practice. Second, to discern the potential consequences of these new forms of collaboration for public trust in public-private collaboration and the state's capacity to respond to a pandemic. The project findings will improve the knowledge base on the conditions for, and consequences of, different models of public-private cooperation and the use of digital technologies for Norway's pandemic preparedness efforts. The project findings will hold relevance for a variety of project end-users, including public health and civil protection authorities, and private (for- and non-profit) actors involved in improving pandemic preparedness and societal security in Norway and internationally.",2020,2023,UNIVERSITETET I OSLO,1206400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,Innovation,,,Norway,Norway,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health leadership and governance,2020 +C09707,301452,"e-Topia: China, India and Biometric Borders","e-Topia refers to the place of the digital in visions of the future. The e-Topia project studies the digital as political, examining how India and China - the two most populous countries in the world - harness ""smart"" technologies to create new economic opportunities, more efficient governance, and more reliable and transparent welfare provision. The project examines policymaking on biometrics, e-governance, the Internet of Things (IoT) and cyber sovereignty in India and China. It also investigates new forms of digital and cyber in/security due to increasing reliance on public-private partnerships, corporate software providers and data storage and processing faciltities, and tensions between the need for global standards and cyber sovereignty concerns. The project highlights the potential of biometric data registration to be coupled with ID scanning across sovereign territories, conflating border control, surveillance and digital governance. Travel between India and China is on the rise, although their high-altitude border remains unresolved. As the Asian contribution to the global smart technology market continues to grow, the relationship between India and China is increasingly dependent on the compatibility of their digitalization efforts. A key contribution of e-Topia is to study new forms of cyber-governance and its employment in the delivery of services, surveillance and border control in both the Asian giants, examining the trade-offs of e-governance solutions such as vulnerability to digital crime, ethnic profiling, monitoring, surveillance, and loss of privacy. With the introduction of biometric data registration and digital identification programs in a growing number of countries across the world, concerns about cyber insecurity and digital vulnerability are mounting. e-Topia will generate new knowledge on the e-governance and IoT strategies of India and China, their digital relations, and their common ""e-Topian"" dreams.",2020,2024,Nasjonale samfunnsvitenskapelige institutter,1392000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,South-East Asia | Western Pacific,,,,Norway,India | China,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health leadership and governance,2020 +C09708,300816,"The Social Gradient in Mental Health. A Long-Term Longitudinal Study Integrating Survey Data, Register Data, and Molecular Genetic Data","The project aims to provide novel information about social gradients of a wide range of mental health problems, including depression, anxiety, eating disturbances, conduct problems, alcohol use, smoking, and illicit drug use. The project will examine (a) how social gradients in mental health develop from adolescence into middle adulthood; (b) how polygenic risk for mental health problems is related to social marginalization; (c) how socio-economic status and social marginalization interact with genetic risk in predicting mental health problems, and (d) how social gradients vary according to societal contexts. The project utilizes data from a large scale, longitudinal study (Young in Norway Longitudinal), spanning from adolescence over 28 years and which combines survey, register, and molecular genetic data (N=2,600). Moreover, two other large-scale representative samples of Norwegian adolescents are used to examine geographical variations in social gradients and how gradients change across time. Growth curve analyses will be used to model trajectories of mental health problems and to examine how social marginalization is related to such trajectories. Polygenic risk scores are constructed to examine how social marginalization interacts with genetic risk. Multilevel analyses will be conducted to examine how social gradients vary according to societal contexts. The project will be based at the newly established Research Center PROMENTA at the Department of Psychology, University of Oslo, in close collaboration with several national and international researchers. A user-perspective is established by collaborating with among others the Norwegian part of the WHO Healthy Cities Network ""Sunne kommuner"" and by consulting a reference group. By using a unique combination of different high quality data sources, this project will provide important novel knowledge about the nature of social disparities in mental health problems.",2020,2025,UNIVERSITETET I OSLO,1357200,Human Populations | Other,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09709,316539,RegReSir - Regional Resilience and Sustainable Industrial Restructuring,"The proposed project investigates the effects of the COVID-19 crisis on industrial development patterns and industrial policy in Norwegian regions. When considering the economic consequences of this crisis on Norwegian businesses, the strategic, long-term question remains whether to bounce back to the 'old normal', i.e. to a situation we had before the outbreak of the Corona crisis, or to use this crisis as a departure point towards a 'new normal'. To answer this , the project maps and explains the ability of regions, industries and firms not just to bounce back (adaptation) but also their potential to bounce forward (adaptability) towards new, more sustainable development paths in terms of economically robust, environmentally friendly and socially inclusive industrial activities. Theoretically, the research builds on and adds to evolutionary economic geography to understand the uneven distribution of firm-level and regional capabilities and combines this with insights from socio-technical transition studies to understand the agentic role of firms' innovation strategies and public policies in driving new path development. Methodologically the analysis combines large scale quantitative data on determinants of regional resilience and in-depth qualitative case studies of the uneven impacts and responses to crisis across industries and regions. The research will provide analytical tools and policy-relevant insights how sustainable and digital industry restructuring unfolds in different ways across different types of regions. Given its strategic importance for the Norwegian economy the project emphasis resource-based industries (seafood/aquaculture, maritime, offshore renewable energy technologies and bioenergy/biomaterials). Through a focus on policy experimentation we also contribute with insights for policy-making on how to shape industry and innovation policies that balance an expedient recovery with sustainable restructuring across Norwegian industries and regions.",2020,2022,HØGSKULEN PÅ VESTLANDET,580000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09710,316534,Media Innovation Through the Corona Crisis (MICC) - how news media can build and implement innovation ability,"The project ""Media Innovation through the Corona Crisis"" (MICC) addresses the economic impact of the COVID-19 pandemic for the Norwegian news media industry and how news media are pivoting their strategies for business opportunities in order to ensure their role in society. Our central objective is to offer a business perspective on how news media can increase the total value created for all stakeholders, including audience, employees and society as a whole. A key project outcome will be the development of a framework which identifies and analyses factors affecting news media innovation ability and value creation. Our theoretical hypothesis is that news media will create more value if they increase their innovation ability instead of improving their innovation capacity. Combining qualitative and quantitative methods, we will analyze the ability layers of news media organizations which include customer experiences, service systems and business models. The research project will address knowledge needs among policy makers, regulators, and practitioners in the media sector, as well as in the academic field of media and business innovation. Questions are being raised concerning the business model of news media and the value of the Norwegian generous press subsidy system. As the press is overall a conservative industry, stakeholders are also concerned that cultural obstacles and centralized management limit innovation ability. Another concern is the lack of user involvement and customer experience management in media innovation processes.",2020,2022,Vitenskapelige høyskoler,580000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,Innovation,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09711,316599,LabRec - Labor Demand in Crisis and Recovery,"The project consists of three work packages: In the first work package, we start out by tracking changes in job vacancy postings, hires, separations and job growth following the outbreak of COVID 19. We compare the trajectories from 2020, to pre-crisis observations from the same months from 2018 and 2019, by occupations, industries, and regions. These analyses will be in ""real-time"" drawing monthly data at half- or yearly intervals from the fall of 2020. We follow both online job vacancy postings, hires, separations and job growth. The focus in the initial phase will be to study the development of occupations, industries, and regions that are most likely to be affected by the political measures and behavioral responses by individuals and firms, with characteristics such as direct human contact, travel and transport dependency, conditions for home- and teleworking etc. In the next phase it will be important to identify spillover effects to other industries and occupations, and the responses to new challenges in the aftermath of the pandemic, such as likely drops in domestic and international demands, broken international value chains, a decline in oil prices, a possible financial crisis, that again are likely to change the trajectories of labor demand. In the second work package, we add data on labor productivity of firms, and analyse how the crisis impacts productivity growth, job reallocation, inequality, and polarization in the labor market. We depart from underlying trends in productivity and changes in relative demand for different types of labor, and study the extent to which these trends are magnified or ameliorated during the different phases of the downturn. The third work package is comparative. We use nearly real-time data on job postings in Norway, Sweden, Denmark and the US, coupled with nearly real-time data on new hires, new separations and net job growth, we will map labor demand from January 2020, into the crisis and onward.",2020,2022,Nasjonale samfunnsvitenskapelige institutter,580000,Human Populations | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09712,316579,Adaptive measures for non-private transport to the Covid-19 Pandemic (CODAPT),"The transport sector and mobility solutions more broadly are in a transition from a private car based fossil fuel burning system, towards a less polluting future. This sustainability transition has been taking place slowly. In Norway it has its two most prominent features are the support mechanisms for electric vehicles and the zero-growth objective for urban mobility. The first, focuses on reducing GHG-emissions within the current mobility regime. The second, focuses on changing mobility behavior. The Covid-19 outbreak has come as a landscape level shock. This creates a situation that is sparsely described in academic transition literature. How does this affect the ongoing transition? We look into how the Covid-19 shock influences the mobility sector along three different paths. First, we focus on labor, where the availability of support mechanisms is different between new and established actors. Established actors mostly operate on public contracts, where income risk is minimal. The smaller and new actors on the other hand, face a massive drop in demand, while the support mechanisms have mechanisms that limit the payout to these actors, as they have a deductible and use previous years' turnover as a reference. Second, focusing on effect on the sustainability transition, the project looks at how the covid-19 outbreak changes the use and perception of new and less polluting modes of transport. Apart from the obvious, compulsory and temporary adjustment in mobility behavior, does the outbreak accelerate or disrupt the sustainability transition? Thirdly, focusing on desired mode choice, the project looks at how a change in valuation of factors such as crowding on public transport modes, affect the social cost of such services. The project will develop a tool that can help optimize the transport policy response, so that the objectives, maintaining mobility accessibility and reducing the spread of the virus, can be achieved at lowest possible social cost.",2020,2022,Miljøinstitutter,580000,Human Populations,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09713,316585,"RelinC: The role of research, skilled labour and innovation in the Coronacrisis.","The project aims at understanding the role of firm-level innovation in promoting economic resilience to pandemic crises. The project bases upon the scientific literature on evolutionary economics and innovation studies, using concepts like adaptation and selection for understanding, in real time, the consequences of a pandemic crisis on a national economy. Empirically, the country under study will be Norway: by analysing a wide array of historical data, a clear picture of the innovation patterns of Norwegian firms will be described. To this purpose, a taxonomy of firms, built from firm-level and employee-level data, will be used to categorize Norwegian firms according to their research, development and innovation patterns. The project will then dig into real-time information on crisis-related bankruptcies and on policy measures aimed at struggling enterprises, in order to understand which parts of the innovation landacape of Norway, as represented by the firm-level innovation categories outlined above, seem to be most resilient to the crises. A main assumption of the project is that different innovation patterns could lead to crisis resilience. Finally, an update of a comprehensive firm survey on R&D and innovation will allow to investigate how the innovation landscape itself is going to change during and following the pandemic crisis.",2020,2022,Nasjonale samfunnsvitenskapelige institutter,580000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,Innovation,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09714,316453,C4: COVID-19 and Human Capital: Cataclysm and Catalyzer,"The COVID-19 pandemic started as a medical crisis that quickly turned into a recession as governments introduced measures that locked-down large parts of the economy. Even for firms not in lockdown, a steep decline in demand forced a large number of firms to make dramatic changes to how they invest, deploy, and manage their human capital. This raises the general question of how the pandemic impacts firms' human capital decisions, and the economic and labor market consequences this implies - both for firms and individuals. Independently of the crisis, firms were already (to varying extent) going through processes of digitalization. It seems reasonably clear that the pandemic will accelerate this digital transformation. It pushes a wide range of business activities online, some of which will lead to lasting changes in organizational- and consumer-behavior. The crisis has thus encouraged firms to implement digital technologies earlier than anticipated, and it seems to have rewarded firms that were highly digitalized before it started. We therefore believe that to understand the economic- and labor market consequences of the COVID-19 pandemic, it is important to realize that human capital decisions following the crisis and the process of digital transformation of the economy are intertwined. The key key to make significant progress on all these issues are two things. One is higher quality data. We need to be able to integrate data on characteristics of firms and industries, with data on the characteristics of individuals and government interventions in a common dataset to understand their interactions and relative effects. To better understand the dynamics of the crisis we also need real time data to observe changes as the crisis unfolds, rather than retrospective data. The other key thing needed is an interdisciplinary group of researchers who can bring a multitude of theoretical and analytical approaches to the data. Our project aims to do both.",2020,2022,NORGES HANDELSHØYSKOLE,464000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,Data Management and Data Sharing,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09715,316592,The Coronavirus Crisis: Development of Capabilities on Measuring and Managing Its Effects in the Norwegian Service and Food Industries,"The negative effects of the coronavirus crisis on the Norwegian economy as a whole and the Norwegian service and seafood exports industries have been significant. The restaurant, fast food as well as travel sectors experienced fall in turnover of up to 90% due to the reduced consumer spending. Also, sales in physical stores, bank branches, training centres, etc. have been negatively affected by the fallout of this unprecedented event. Furthermore, exports of Norwegian seafood fell by 8% in April 2020 relative to 2019, as a result of the coronavirus crisis. The value of exported salmon fell by 13% in April 2020 relative to 2019. On the consumer level, the coronavirus crisis triggered the phenomena of increased consumption of less healthful products and services, nationalism and materialism. Another significant consequence of the crisis is increased consumer resistance to service innovations. This fallout of the crisis presents considerable threats for companies in the Norwegian service and seafood exports industries. More importantly, due the extraordinary nature of this crisis many companies in these industries lack the necessary competence to measure and manage its effects on their operations. In order to meet these challenges and to protect and manage the strategically important for Norway industries - food, services and seafood exports, this project focuses on the development of economic analysis and market intelligence capabilities of the industry partners in the project - Virke, the Norwegian Seafood Council and their member companies. Each of the partners´ industries will be subject to case studies that will form the foundation for research in this investigation and the development of corporate capabilities.",2020,2022,Nasjonale samfunnsvitenskapelige institutter,580000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09716,317725,Smart Workspace past Covid-19,"The work environment has changed significantly over the last decade with more working from home, video meetings and work in open landscapes. With Covid-19, this change has been accelerated as organizations and employees have been forced to adopt new ways of working. Even after the measures of Covid-19 has ceased, it is expected that more people will work from home, more meetings will be done over video and the office will be where you go for live discussions and social interactions with your colleagues, partners and customers. Thus the work place needs to be more dynamic and flexible going ahead. Having office space that is not suited for the new way of working will give unhappy employees, low productivity and lower utilization of the office which is both costly as well as an environmental challenge. Real estate is the second main cost for companies, and an area that has been overlooked for too long. Before Covid-19, companies reported that up to 40% of meeting rooms are booked but unused , while 40% of employees report wasting up to 30 minutes a day searching for spaces to collaborate, and 50% of meetings occur with just one or two people in the space . The accumulated cost of unused offices, energy and lack of productivity accounts for over a billion NOK in Oslo alone and almost a trillion euros worldwide, yearly! Unless offices adapt and are provided with tools so user needs are better matched, the waste in productivity and real estate will increase drastically leading to both economical as well as environmental losses. This project will provide solutions to these problems by: 1) Optimize real estate by a) increasing desk utilization, b) eliminating the fake usage problem and c) matching room sizes with actual needs 2) Augmenting user satisfaction by a) quickly guiding users, b) delivering resources closer to the time of consumption and c) finding colleagues in real time 3) Ensuring policy and safety including a solution for social distancing.",2020,2022,Næringsliv,1566000,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C09717,316533,CONSIGN - Effects of Covid-19 on reliability Of National Supply In a Global Nexus,"The COVID-19 pandemic has led to major changes and disruptions for Norwegian business and industry, not in the least for freight transport. With CONSIGN, ramifications of the current crisis will be studied through three veins: 1) analysis of real-time and time-series data from fleet management systems for a large sample of trucks; 2) screening of changes in economic activity in different sectors based on detailed shipment data from the three largest freight forwarders in Norway, and 3) in-depth case studies among important actors within Norwegian transport and supply chains. Combined, this yields insights into economic and cost impacts of disruptions on Norwegian freight transport and transport-dependent industries in the economy as a whole, reliability of supply for the Norwegian society and approaches to tackle transport and supply chain challenges. CONSIGN will also study effects of public support measures, by assessing the timing of changes in activity levels against the timing of policy measures and restrictions. Further, CONSIGN will assess whether changes are characterized by short-term shocks, or stabilize at new levels. The latter can provide insights into response time and adaptability for firms and public authorities. Through collaboration with ten major actors from industry, CONSIGN is strongly anchored with practice. This ensures relevant and real life insights, and facilitates very comprehensive analyses that cover a large share of the Norwegian economy and supply chains across a broad range of industries, all transport modes, and with a high level of detail both in geography and time. Due to the abruptness of disruptions and their nature, the corona situation allows for a unique stress test of the robustness of supply chains for Norwegian society and business, and understanding the veins through which the current situation affects transport and reliability of supply is crucial for the design of effective political responses and policy measures.",2020,2022,Miljøinstitutter,487200,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C09718,316475,The corona crisis and its economic consequences,"Based on close to real-time register data, we will document the magnitude, dynamics and socio-economic characteristics of the corona crisis and its recovery, the impact of the various government crisis measures, along with analyses of the economic recovery across individuals, families, businesses, sectors and regions. The research activities will be partly descriptive (what happened during the crisis and its recovery?), partly designed to identify mechanisms (why did it happen?), and partly designed to evaluate effects of policies (what should we do about it?). Central topics include • An analysis of individual job losses, subsequent unemployment durations and their ultimate outcomes • An examination of the distributional consequences of the crisis and the extent to which social insurance programs contributed to a fair burden sharing • A closer look at spillovers across industries and the economy's ability to reallocate workers and entrepreneurs from declining to growing industries • An examination of the matching efficiency between unemployed workers and vacancies, with the aim of identifying mismatches related to skills and geography • A study of how migration patterns responded to the crisis, and how this affected job opportunities for native workers and the availability of labor demanded by Norwegian firms. • An examination of how the crisis affected entrepreneurship and an evaluation of the extent to which Norwegian labor market policies are designed to encourage the creation of new jobs. • An analysis of how the crisis affected educational choices during the Spring 2020 • An effect analysis of Norwegian labor market programs during an era of mass layoffs • An assessment of the major economic support packages implemented by the Norwegian government, including the changes in the unemployment insurance program and the introduction of cash support to cover firms' unavoidable fixed costs • An examination of the role expectations for firms' investment behavior",2020,2022,Nasjonale samfunnsvitenskapelige institutter,580000,Human Populations,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C09719,316244,Digital outpatient clinic with home follow-up,"For a long time, outpatient follow-up of patients stopped at the country's hospital in the first phase of the pandemic fight against the corona virus. Important treatment for thousands of patients was postponed because it was not safe to visit the hospitals for the most vulnerable patients. ""Overnight"" a number of outpatient departments switched to using video consultation to avoid physical close contact. The ""Digital Outpatient Clinic"" project will take this to a new level, where video consultation is only one part of an improved clinical practice to increase safety and provide better treatment of outpatient patients, an important step in achieving ""the patient's healthcare"". In addition to benefits for patients, the project will co-create a more digitally based outpatient follow-up for doctors and nurses in the specialist health service. Clinicians will participate in creating the new work processes together with professional service designers. Dignio will further develop its system for digital home follow-up to fit into the new way of working. Both clinical trials and further development of the system will take place in collaboration with the Intervention Center at OUS, which has a national responsibility to ensure safe development and introduction of new methods. The cancer outpatient clinic at UNN will participate together with several outpatient clinics at OUS to test the solution in daily operations. The Center for Connected Care (C3), also at OUS, will assist with service design and follow-up research on the effect such outpatient treatment will have on patients, health personnel and organizations (including sustainability goals). The hospital partner and DIPS will ensure a good interaction between the hospital's existing systems and Dignio's solution for home follow - up. The Norwegian Cancer Society also participates as a supporter and representative of patients' interests.",2020,2022,Næringsliv,893200,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health service delivery",2020 +C09720,316294,Targeted COVID-19 treatment using neutralizing antibody,"Pending a vaccine and other effective treatments, Norimun AS, together with NTNU and Oslo University Hospital (OUS), has taken the initiative to produce targeted antibodies against SARS-CoV-2, the virus that causes COVID-19. To meet the demand for antibodies that can neutralize SARS-CoV-2, it must be produced in large quantities at a cost-effective price. Furthermore, antibody formulations that meet medical safety requirements must be prepared and a clinical trial on humans must be designed. An effective antibody preparation, which acts as a passive immunization, will be of great benefit to critically ill patients but also to healthcare professionals who are exposed to a high risk of infection. The main objective of the project is to produce antibodies with a neutralizing effect that can be offered to COVID-19 patients and administered either orally, by inhalation or by transfusion.",2020,2021,Næringsliv,464000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C09726,unknown,Establishment of a revolutionary new coronavirus test method using next-generation automation technology that enables multi-sample testing,,2020,-99,Kitasato University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09727,unknown,Comprehensive automation of PCR tests for emerging re-emerging infectious diseases and whole-genome sequence analysis centered on humanoid general-purpose robots,,2020,-99,University of Tsukuba,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C09728,unknown,Research and development on new coronavirus screening test method using AI nanopore,,2020,-99,Osaka University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09729,unknown,Research to build a social examination system using saliva for COVID-19,,2020,-99,Keio University,,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09730,unknown,Demonstration and comparative research of a fully automatic genetic testing system that can safely and mass-process new coronavirus infections,,2020,-99,Kyoto University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09731,unknown,Development of a simple and accurate COVID-19 immunity acquisition test system that can handle large-scale tests,,2020,-99,FUJIFILM Corporation,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Immunity, +C09732,unknown,Development of semi-quantitative and rapid neutralizing antibody titer measurement method in anticipation of the post-vaccine era of new coronavirus infection,,2020,-99,Osaka City University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity, +C09733,unknown,Research for the development and demonstration of a new high-performance mask (equivalent to N95) for preventing new coronavirus infection,,2020,-99,National Research and Development Corporation National Cardiovascular Center,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C09734,unknown,Analysis of functional materials that prevent the spread of coronavirus infection and their interface structures,,2020,-99,Kyoto Prefectural University of Medicine,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C09735,unknown,Identification of COVID-19 prognosis-related immune factors based on analysis of SARS-CoV-2 cross-reactive T cells and B cells in healthy and convalescent patients uninfected with Vietnam SARS-CoV-2,,2020,-99,Kyoto University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C09736,unknown,Vaccine development for new coronavirus infection (COVID-19) in Japan using self-propagating RNA technology,,2020,-99,VLP Therapeutics Japan GK,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09737,unknown,Vaccine development for new coronavirus infection (COVID-19),,2020,-99,"Shionogi Pharmaceutical Co., Ltd.",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09738,unknown,Development of inactivated vaccine against new coronavirus infection (COVID-19),,2020,-99,"KM Biologics Co., Ltd.",,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09739,unknown,RNA vaccine development for new coronavirus infection (COVID-19),,2020,-99,"Daiichi Sankyo Co., Ltd.",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09740,unknown,Development of mRNA-1273 vaccine against new coronavirus,,2020,-99,Takeda Pharmaceutical Company Limited,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09741,unknown,Development of NVX-CoV2373 vaccine against new coronavirus,,2020,-99,Takeda Pharmaceutical Company Limited,,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09742,unknown,Clinical development of DNA vaccine targeting the new coronavirus (COVID-19),,2020,-99,"AnGes MG, Inc.",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase), +C09743,unknown,Development of live attenuated vaccine against new coronavirus infection (COVID-19) II,,2020,-99,University of Tokyo,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09744,unknown,Development of oral vaccine against new coronavirus infection (COVID-19),,2020,-99,Kobe University,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09745,unknown,New Coronavirus Vaccine Phase I / II Study Using Third Generation RNA Vaccine Technology,,2020,-99,Fujita Medical University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial, +C09746,unknown,Development of new coronavirus infection vaccine using measles virus vector,,2020,-99,University of Tokyo,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Japan Agency for Medical Research and Development (AMED),Japan,Western Pacific,Western Pacific,Western Pacific,,,,Japan,Japan,"Vaccines research, development and implementation",Pre-clinical studies, +C09751,unknown,Development of Microfluidic Bioreactors for COVID-19,,2020,-99,Fullgen SRL,65758.62,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C09752,unknown,Isolated intubation system,,2020,-99,Galhaar SAS,58689.35,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C09753,unknown,Industrial-scale production of a simplified molecular kit for the detection of COVID-19,,2020,-99,Neokit SAS,187517.82,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C09754,unknown,Point-of-care device for monitoring COVID + patients in ICU,,2020,-99,Gisens Biotech SA,173517.65,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management", +C09759,RIA2020EF-2975,"ANTICOV: Preparation of an open-label, randomised, comparative, adaptive, multi-country study to test the safety and efficacy of new therapeutic strategies against standard of care in mild SARS-CoV-2 patients in resource-constrained settings",,2020,-99,Drugs for Neglected Diseases initiative (DNDi),220000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Phase 3 clinical trial,2020 +C09760,RIA2020EF-2977,ASCENT: Acceleration of novel coronavirus serological test development and seroprevalence study: an African-European initiative,,2020,-99,Institut National de la Santé et de la Recherche Médicale (INSERM),554965.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09761,RIA2020EF-3005,MozCOVID: COVID-19 surveillance in rural Mozambique for prompt and effective response,,2020,-99,Fundação Manhiça,600000,Unspecified,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa,,,,Mozambique,Mozambique,Epidemiological studies,Disease transmission dynamics,2020 +C09810,20/09377-3,Sudden anosmia: comparative study of intensity and evolution in patients with acute SARS-Cov2 infection and other respiratory viruses,"Smell represents an important sense that allows human beings to understand and interact with the environment. Approximately one third of the sudden loss of smell is caused by an acute viral infection of the upper airways (URTI), usually due to problems in the conduction of odorous molecules to the olfactory fossa, with complete reversal in most cases. Among the clinical manifestations that have drawn attention during the infection caused by SARS-CoV-2 (COVID-19) are olfactory and gustatory changes. According to the first descriptions, the changes in smell have been more intense and of early onset, generally not accompanied by rhinorrhea or nasal obstruction, suggesting a predominant neuroepithelial dysfunction and not an obstructive origin of the olfactory cleft. Another relevant fact is that many patients with COVID-19 have initially manifested themselves only with olfactory changes, even before complaining about other symptoms of greater suspicion, such as fever, odynophagia, cough or dyspnoea. Finally, the olfactory recovery prognosis is not yet fully known in patients affected by COVID-19. Faced with an emerging disease, highly transmissible and of great repercussion for the health and economy system in global dimensions, the natural history of COVID-19 is still little known, particularly in terms of smell changes. In this multicenter study involving several Brazilian cities, we propose to prospectively evaluate the evolution of olfaction (measured by quantitative and qualitative test of smell - modified CCRC test) as well as the positivity of a panel of respiratory viruses in the nasopharynx detected by PCR, including SARS-CoV-2) in individuals with sudden anosmia. In addition, patients who continue to complain of anosmia after 60 days will be investigated with nasofibroscopy, collection of cells in the olfactory region (cytobrush) and magnetic resonance imaging. The results of this study may show the prevalence of SARS-CoV-2 in cases of sudden anosmia, identify the positive predictive value of anosmia as a marker of COVID-19, as well as understand the natural history of anosmia in cases of COVID-19 in relation to to other viral pictures. We hope that the conclusions of this study can assist in the prevention and dissemination of the disease, as well as guiding patients on the prognosis in relation to the natural behavior of the disease. (AU)",2021,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C09811,20/07905-2,Influence of authentic leadership on the patient safety climate in the context of the COVID-19 pandemic,"More flexible, authentic and contemporary styles of leadership have contributed to the satisfaction of workers and patients, as well as the reduction of adverse events. Especially in the current situation, in which the world is experiencing the COVID-19 epidemic, authentic leaders are essential, given that they have the potential to lead the team towards positive results related to patient safety. Thus, this study aims to analyze the relationship between the nurse's leadership and the safety climate of hospitals that serve patients affected by COVID-19. This is an observational, analytical, cross-sectional study, to be carried out in six public and private institutions in the Federal District and the State of São Paulo that are a reference for the care of COVID-19. The population will consist of nurses, nursing technicians and assistants who work in the medical clinic and intensive care units of these institutions who will answer the Authentic Leadership Questionnaire (ALQ), Rater version, and the Safety Attitudes Questionnaire (SAQ). For the analysis of the characterization data of the subjects, descriptive statistics will be used. The numerical variables will be analyzed with the student's t test, for comparisons of means between the groups; and categorical variables with the chi-square test, to compare proportions between groups. The relationship between security climate and perceptions of authentic leadership will be assessed through hierarchical regression analysis. The project will be submitted to the Research Ethics Committee of the Ribeirão Preto School of Nursing - USP, in order to comply with the requirements of Resolution 466/2012 of the National Health Council. This study has the potential to generate results that will contribute to the practice, enabling changes in future behaviors, especially in this context of a pandemic, in which effective leadership it is essential to ensure the provision of safe and quality care. (AU)",2021,2023,Universidade de São Paulo,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Health Systems Research,Health service delivery | Health leadership and governance,2021 +C09812,20/05623-0,"Diagnosis of SARS-CoV2 infection, in different biological materials, in people infected with this virus","In general, the diagnosis of SARS-CoV-2 infection worldwide occurs in the acute phase of the disease and through the identification of the virus in samples collected by nasopharyngeal swab and eventually saliva. Little is known about the presence of this agent in other biological materials and at different stages of the disease. Likewise, little is known about the association of the excretion of this agent in these secretions and the immune-humoral response. Clarifying this information could assist in understanding the natural history of the disease and assist in the diagnosis and management of these patients, clarifying important aspects of interpersonal, hospital and community transmission of this agent. Objectives 1 - Investigate the presence of SARS-CoV-2 in a naso pharynx, saliva, urine, blood and feces swab, during the acute and convalescent phase of infection in immunocompetent and immunocompromised patients; 2 - Investigate the presence of SARS-CoV-2 in saliva or naso-pharyngeal swab of contacts of patients with Covid-19; 3 - Correlate the presence of SARS-CoV 2 in these biological materials and the titers of neutralizing antibodies and IgG-type antibodies by ELISA; 4 - Investigate the SARS-CoV-2 permanence and infectivity rate in these patients during the acute and convalescent phase of COVID-19. Methodology - This is an observational, prospective study, to be carried out on patients and asymptomatic contacts of these patients, attended at the Hospital das Clínicas, USP Medical School, Cancer Institute of the State of São Paulo (ICESP) and in the municipality of São Caetano do Sul, diagnosed with SARS-CoV-2 infection. 125 patients will be included, divided into 3 groups of patients: 1 - Symptomatic patients without diagnosis of any previous immunosuppression (50 patients); 2 - Symptomatic patients diagnosed with solid tumors or candidates for Hematopoietic Stem Cell Transplantation (25 patients); 3 - Asymptomatic contacts of these patients (any group - 50 patients). Blood, urine, saliva, and naso pharyngeal and anal swabs will be collected for 5 consecutive weeks, with intervals of one week (days 1, 7, 14, 21, 28) starting up to 72 hours from the time of diagnosis in all patients in groups 1 and 2. For patients in group 3, only saliva and naso pharynx swab will be collected on day 1. For the detection of anti-SARS CoV 2 antibodies, ELISA serological techniques and the neutralization assay will be used. . For viral identification, molecular biology and viral culture techniques will be used. Duplex quantitative assays (internal control and N or E gene) for SARS-CoV-2 will be carried out according to adapted protocols, with the primers and probes for the real-time PCR assay. The viral isolation will be carried out in a security laboratory level 3 (NB-3), and the samples will be subjected to isolation in VeroE6 cells, known to be susceptible to Coronavirus. (AU) and the samples will be subjected to isolation in VeroE6 cells, known to be susceptible to Coronavirus. (AU) and the samples will be subjected to isolation in VeroE6 cells, known to be susceptible to Coronavirus. (AU)",2021,2023,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease susceptibility",2021 +C09813,20/09378-0,"Structural, functional and inflammatory evaluation of the lungs in patients after infection with SARS-CoV-2 without previous lung disease","A new Coronavirus (SARS-CoV-2) is the etiologic agent of the disease called COVID-19, is causing thousands of mild, moderate and severe infections worldwide and is the cause of the biggest pandemic in the last 50 years. We do not know how many people have been infected with SARS-CoV-2, because many are asymptomatic, nor do we understand why some individuals have mild symptoms while others have severe illness. We also do not understand why some individuals with mild and moderate forms can have great acute pulmonary involvement, without the need for admission to the ICU and with clinical recovery. As for SARS -CoV-2, it is known that it fixes, multiplies and spreads a lot in the pulmonary airways, which could cause sequelae even in mild and moderate forms of COVID-19. Objective: To verify whether children and adolescents who had mild, moderate and severe forms, and adults with mild and moderate forms of COVID-19, present changes in lung structure, lung function and clinical and psychological impact on quality of life, resilience, anxiety and depression, six months after the disease. Casuistry and methods: An observational, analytical, prospective cross-sectional study will be carried out with patients who had COVID-19. The following tools will be used to assess the structure, lung function and clinical and psychological impact of the disease: high-resolution computed tomography of the chest, chest ultrasound; spirometry, impulse oscillometry system (IOS), plethysmography, measurement of the exhaled fraction of nitric oxide (FeNO), measurement of transcutaneous hemoglobin oxygen saturation, manuvacuometry, six-minute walk test (6MWT) and standardized tests on quality of life, depression and anxiety. The numerical variables will be analyzed by obtaining measures of central tendency as mean and median, as well as by measures of variability such as standard deviation and variance. All statistical tests that are used will be performed considering a significance level of 5% (pd0.05). The project is being submitted to the Institution's Ethics Committee. The main goal of this study will be to verify lung changes in subjects who were infected with SARS-CoV-2 and had COVID19. We believe that we will be able to find changes, which will be possible to be managed, to improve the health and the quality of life and the health of these individuals. The research may provide an understanding of pulmonary impairment and temporal sequelae caused by an inflammatory response caused by COVID-19, even in mild cases. Based on this understanding, it is intended to develop strategies to delay and minimize sequelae from COVID-19, reducing the deterioration of lung structure and function. Keywords: pulmonary function, COVID-19, quality of life, spirometry. (AU)",2020,2022,Universidade Estadual de Campinas (UNICAMP),,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts,2020 +C09814,20/07765-6,Cytokine storm in the covid-19 patient: contribution of adipose tissue,"Hypothesis: The white adipose tissue (WAT) contributes, as one of the main endocrine glands, to the cytokine storm and the systemic effects of the infection.Justification: i) WAT is an important component of the inflammatory response in cachexia, a systemic disease in which hypoxia, inflammation and fibrosis occur in the main organs. Therefore, it is possible to expect similarities, given the recent description of the effects of Covid19 on organs / tissues19 ii) ii) WAT secretes all major inflammatory cytokines, eicosanoids and also adipokines. There is no literature available on the expression of inflammatory / autacoid cytokines and adipokines in patients with WAT from COVID19 Objectives: 1. Examine the morphology of WAT, immune infiltration, fibrosis and expression of inflammatory factors 2. Investigate intracellular NFKB (adipocyte and monocyte) and inflammatory pathways 3. Study the load of exosomes derived from WAT. Casuistry and experiments: a) SAMPLES: WAT (subcutaneous and visceral deposits), plasma University Hospital (HU-USP): 40 patients with positive Covid-19 test, submitted to emergency surgery; 20 negative patients for the Covid19 tests, who underwent the same surgeries Faculdade de Medicina-USP: samples obtained from autopsies of patients who passed Covid19 (20); equal number of control samples b) Experiments: WAT: ¾ Histological analysis of tissue (light and electron microscopy) ¾ FACS exam study of infiltrated immune cells ¾ Multiplex assays for inflammatory cytokines, proteins involved in hypoxia, proteins related to fibrosis pathways PCR PCR in real time for the same factors and microRNA analysis ¾ Western blot for evaluation of phosphorylated proteins in the pathways of interest Lip Lipidomics of Incub tissues Incubation of explants and separation of exosomes and subsequent analysis (lipidomics, miRs ) Plasma: ¾ Inflammatory / metabolic profile: quantification of circulating markers of inflammation, cardiometabolic disease, neuropeptides, adipokines and hormones (insulin, cortisol, testosterone, estradiol) PCR, cytokines, neuropeptides, adipokines, glucose, lactate, creatinine, insulin, cortisol Plasma / lipidomic metabolomic metabolism; Separation Exosome separation and load evaluation (AU) quantification of circulating markers of inflammation, cardiometabolic disease, neuropeptides, adipokines and hormones (insulin, cortisol, testosterone, estradiol) PCR, cytokines, neuropeptides, adipokines, glucose, lactate, creatinine, insulin, cortisol Metabol of plasma / lipid metabolism; Separation Exosome separation and load assessment (AU) quantification of circulating markers of inflammation, cardiometabolic disease, neuropeptides, adipokines and hormones (insulin, cortisol, testosterone, estradiol) PCR, cytokines, neuropeptides, adipokines, glucose, lactate, creatinine, insulin, cortisol Metabol of plasma / lipid metabolism; Separation Exosome separation and load assessment (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C09815,20/06438-1,Composition of immunoglobulin CDRs: geography and coevolution with fever-inducing pathogens,"Neutralization of a pathogen requires that the link between the specific antibody and the pathogen has optimal affinity. This affinity is determined by the landscape (loads and formats) of the amino acids that make up the regions that will come into contact. The pathogen can escape the host's immune system by changing these amino acids, while the host's immunoglobulin repertoire presents strategies that result in high mutation rates in the contact regions, the CDRs. The high temperatures of the fever produced during a pathology, can alter the conformation of these interface regions, improving or worsening the neutralizing capacity of an antibody. In this project, we will evaluate the amino acid composition of the CDRs regions of neutralizing antibodies against P. falciparum and SARS-CoV-2, in order to determine what is the contribution of the repertoire generated by the germ line in contrast to that obtained by affinity maturation, which occurs under the influence of the pathogen. We will compare the germline repertoires of several modern populations, distributed in different geographic locations, with those obtained from ancestral populations (Neanderthals, Denisovans, etc.). We anticipate that this project will contribute to the understanding of the co-evolution between pathogens and immunoglobulins on two fronts: (i) the influence of geography and local diseases as a selective pressure on the immunoglobulin repertoire, and (ii) the potential contribution to conformational changes in neutralizing immunoglobulins, when under a febrile episode, for the pathogenesis of malaria and COVID-19. (AU) that occurs under the influence of the pathogen. We will compare the germline repertoires of several modern populations, distributed in different geographic locations, with those obtained from ancestral populations (Neanderthals, Denisovans, etc.). We anticipate that this project will contribute to the understanding of the co-evolution between pathogens and immunoglobulins on two fronts: (i) the influence of geography and local diseases as a selective pressure on the immunoglobulin repertoire, and (ii) the potential contribution to conformational changes in neutralizing immunoglobulins, when under a febrile episode, for the pathogenesis of malaria and COVID-19. (AU) that occurs under the influence of the pathogen. We will compare the germline repertoires of several modern populations, distributed in different geographic locations, with those obtained from ancestral populations (Neanderthals, Denisovans, etc.). We anticipate that this project will contribute to the understanding of the co-evolution between pathogens and immunoglobulins on two fronts: (i) the influence of geography and local diseases as a selective pressure on the immunoglobulin repertoire, and (ii) the potential contribution to conformational changes in neutralizing immunoglobulins, when under a febrile episode, for the pathogenesis of malaria and COVID-19. (AU) with those obtained from ancestral populations (Neanderthals, Denisovans, etc.). We anticipate that this project will contribute to the understanding of the co-evolution between pathogens and immunoglobulins on two fronts: (i) the influence of geography and local diseases as a selective pressure on the immunoglobulin repertoire, and (ii) the potential contribution to conformational changes in neutralizing immunoglobulins, when under a febrile episode, for the pathogenesis of malaria and COVID-19. (AU) with those obtained from ancestral populations (Neanderthals, Denisovans, etc.). We anticipate that this project will contribute to the understanding of the co-evolution between pathogens and immunoglobulins on two fronts: (i) the influence of geography and local diseases as a selective pressure on the immunoglobulin repertoire, and (ii) the potential contribution to conformational changes in neutralizing immunoglobulins, when under a febrile episode, for the pathogenesis of malaria and COVID-19. (AU) and (ii) the potential contribution to conformational changes of neutralizing immunoglobulins, when under a febrile episode, to the pathogenesis of malaria and COVID-19. (AU) and (ii) the potential contribution to conformational changes of neutralizing immunoglobulins, when under a febrile episode, to the pathogenesis of malaria and COVID-19. (AU)",2020,2022,Universidade de São Paulo,,Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C09816,20/08943-5,Investigation of elements induced by the vaccine response in individuals submitted to clinical tests with the ChAdOx1 nCOV-19 vaccine,"This research proposal consists of an unfolding of the international project with samples of volunteers for testing the Oxford-UNIFESP ChAdOx1 nCoV-19 vaccine. The proposal will involve the 2,000 samples of volunteers, and the corresponding periods, to establish mainly a repository for the entire academic community of the State of São Paulo. This repository will be converted into a biobank after the completion of the project, as stated in the current legislation. In addition, the samples stored in the biorepository will be used to perform analyzes of these samples that do not overlap with the ""Primary and secondary outcome measures"", as described in the clinical trial documentation available at ClinicalTrials.gov (National Institutes of Health, ID NCT04400838) . The project will be coordinated by Prof. Luiz Mario Ramos Janini and will include a team of leading researchers in different areas, referring to the specific objectives and research history of FAPESP. The objectives of this project are: (1) to establish a biorepository containing all samples obtained from volunteers before and after vaccination. This biorepository will be available, in accordance with legal procedures, for the entire scientific community of the State of São Paulo, as determined by FAPESP guidelines; (2) to evaluate the neutralization capacity of sera of individuals vaccinated against SARS-CoV-2 strains specific to Brazil and other specific strains of coronavirus to assess cross-immunity; (3) to characterize Brazilian SARS-CoV-2 isolates and to study the sequence variation and evolutionary patterns of the protein ""Spike"" specific to assess the escape potential of the vaccine by modifying the target or epitopes; (4) generate and analyze serum cytokine profiles of volunteers before and after vaccination to assess the inflammatory response and associated effects; (5) analyze and compare the blood transcriptomes of volunteers, by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to assess the impact of the vaccine on differential levels of gene expression and to assess individual variation in the genetic response to the vaccine and (6) to analyze the secretomeome profile in the volunteers' whole blood, before and after vaccination, to evaluate the type of immune response predominant and possible ""priming"" by another coronavirus. (AU) (4) generate and analyze serum cytokine profiles of volunteers before and after vaccination to assess the inflammatory response and associated effects; (5) analyze and compare the blood transcriptomes of volunteers, by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to assess the impact of the vaccine on differential levels of gene expression and to assess individual variation in the genetic response to the vaccine and (6) to analyze the secretomeome profile in the volunteers' whole blood, before and after vaccination, to evaluate the type of immune response predominant and possible ""priming"" by another coronavirus. (AU) (4) generate and analyze serum cytokine profiles of volunteers before and after vaccination to assess the inflammatory response and associated effects; (5) analyze and compare the blood transcriptomes of volunteers, by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to assess the impact of the vaccine on differential levels of gene expression and to assess individual variation in the genetic response to the vaccine and (6) to analyze the secretomeome profile in the volunteers' whole blood, before and after vaccination, to evaluate the type of immune response predominant and possible ""priming"" by another coronavirus. (AU) by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to assess the impact of the vaccine on differential levels of gene expression and to assess individual variation in the genetic response to the vaccine and (6) to analyze the secretomeome profile in the volunteers' whole blood, before and after vaccination, to evaluate the type of immune response predominant and possible ""priming"" by another coronavirus. (AU) by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to assess the impact of the vaccine on differential levels of gene expression and to assess individual variation in the genetic response to the vaccine and (6) to analyze the secretomeome profile in the volunteers' whole blood, before and after vaccination, to evaluate the type of immune response predominant and possible ""priming"" by another coronavirus. (AU) by another coronavirus. (AU) by another coronavirus. (AU)",2020,2025,Universidade Federal de São Paulo (UNIFESP),,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +C09817,20/06073-3,Adaptation and verification of the effectiveness of a program to promote mental health and resilience in children affected by COVID-19,"Pandemics, in general, compromise the psychological system and people's behavior, insofar as they alter the routine, generate insecurity and expose the population to dire realities. In many cases, this adverse context can trigger syndromic conditions resulting from the post-calamity. It can be said that children make up a risk group not only because they are exposed to the virus, but because they experience levels of stress, anxiety and tension in the face of the catastrophe that hit them. Children's reactions to pandemics depend on a number of factors, including how they were dealing with the day-to-day challenges before the disaster; how severe the disaster was and how much it impacted their lives; the people they loved were lost; whether they were separated from their parents or other caregivers; and the type of support systems they have after the disaster. Understanding the situations that produced the pandemic, expanding the network of affective-social support and strengthening family and community bonds are strategies capable of favoring children's resilience processes, since they can imply the construction of social and psychological resources that help them in coping with the misfortunes generated. Based on these considerations, this research project aims to adapt and verify the effectiveness of a psychosocial intervention program aimed at children who have had adverse experiences due to the COVID-19 pandemic. This is a research-intervention type investigation, carried out from a transversal cut and that will use the quantitative and qualitative approaches to evaluate the effectiveness of a psychosocial intervention program developed by Save the Children of Denmark. The program, consisting of 15 sessions, will be tested in a group of approximately 100 children (subdivided, a posteriori, into Experimental Group - GEx - and Espera Group - GEs). Participants will come from 5 Brazilian cities: São Carlos (SP); Fortaleza (CE); Belém (PA); Brasilia DF); Porto Alegre (RS). To verify the effectiveness of the intervention, quantitative and qualitative instruments will be used: i) Children's Depression Inventory - CDI; ii) Child Stress Scale - ESI; iii) Scale of Positive and Negative Affections; iv) Child and Youth Resilience Measure (CYRM) - Child Version; v) Map of the Five Fields (MCC); vi) Field diaries. After the procedure for translating the program manuals (through back-translation), the pre-test, conduct of the intervention, post-test and follow-up will be carried out with both groups. It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) After the procedure for translating the program manuals (through back-translation), the pre-test, conduct of the intervention, post-test and follow-up will be carried out with both groups. It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) After the procedure for translating the program manuals (through the back-translation), the pre-test, conduction of the intervention, post-test and follow-up will be carried out with both groups. It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) conducting the intervention, post-test and follow-up with both groups. It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) conducting the intervention, post-test and follow-up with both groups. It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) It is hypothesized that the participants will present statistically significant improvements in terms of the mental health indicators evaluated and the resilience processes after engaging in the intervention. If the results obtained are in line with the hypotheses raised, the researchers will organize the material to be disseminated among professionals working in the field of promoting psychosocial interventions, so that the program can be replicated in other contexts after the COVID pandemic period. -19. (AU) so that the program can be replicated in other contexts after the COVID-19 pandemic period. (AU) so that the program can be replicated in other contexts after the COVID-19 pandemic period. (AU)",2020,2022,Universidade Federal de São Carlos (UFSCAR),,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C09818,20/07231-1,Exploring the emotional effects of the COVID-19 pandemic on undergraduate health care students,"A pandemic scenario, such as COVID-19, corroborates a state of mental stress worldwide. Studies have been shown to affect even health professionals. The rapid evolution of an outbreak, which spread across all continents, has generated global concern, not only because of the number of cases of infected people and deaths, but also because of the great global biopsychosocial impacts caused, which may exceed the capacity to cope with affected people. In relation to students in the health area, this situation can be similar. Bearing in mind that, in the future, these students will be the next health professionals, it is essential to analyze their emotional stability in the face of this pandemic situation, in addition to measuring whether greater knowledge in the field of health contributes or not to an increase in mental stress. Goals: To evaluate the frequency of symptoms of depression, anxiety of undergraduate students in health courses through recommended scales, in addition to knowing their reactions and perception about the implementation of Digital Teaching (EAD) in this period of Pandemic of COVID-19. Methods: Using the e-mail resource, all students regularly enrolled in the medical, nursing, pharmacy and speech therapy courses at Unicamp and medicine and dentistry at Faculdade São Leopoldo Mandic will be invited to participate in the study. After agreement and consent, a link will be sent to students, by e-mail, to access the data collection form comprising the following instruments: State-Trait Anxiety Scale (STAI) as a reliable measure to assess trait and anxious state, Beck Depression Scale (DBI II) as a reliable measure to assess symptoms of depression, and a closed questionnaire, designed especially for this study. Graduates who accept to participate and who respond to the data collection form will be sent a new invitation to participate in a Focus Group, also to be carried out online, as the second component of the study. Data analysis: It is expected to determine the frequency of students in the health field who showed symptoms of depression and anxiety resulting from the pandemic and to know their reactions and perceptions about the distance study carried out at this time. All data obtained with the aid of the Google Forms program (study form), for further analysis will be used for parametric and nonparametric comparison tests, according to the data distribution. Initially, an analysis will be made in relation to the students' responses about the frequency of signs related to their mental health, specifically signs of anxiety and depression, based on the recommended scales. Then, specific characteristics of each student will be taken into account, analyzing their context in the current pandemic moment and their assessment in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) an analysis will be made in relation to the students' responses about the frequency of signs related to their mental health, specifically signs of anxiety and depression, based on the recommended scales. Then, specific characteristics of each student will be taken into account, analyzing their context in the current pandemic moment and their assessment in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) an analysis will be made in relation to the students' responses about the frequency of signs related to their mental health, specifically signs of anxiety and depression, based on the recommended scales. Then, specific characteristics of each student will be taken into account, analyzing their context in the current pandemic moment and their assessment in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) based on the recommended scales. Then, specific characteristics of each student will be taken into account, analyzing their context in the current pandemic moment and their assessment in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) based on the recommended scales. Then, specific characteristics of each student will be taken into account, analyzing their context in the current pandemic moment and their evaluation in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) analyzing its context in the current pandemic moment and its evaluation in relation to digital teaching (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) analyzing its context in the current pandemic moment and its evaluation in relation to digital education (EAD). The data obtained in the Focus Groups will be treated and analyzed according to the content analysis methodology. Expected results: Emotional changes during this time of global health crisis are expected, but we need to know the real impacts of this, on the students' lives so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) in the lives of students so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU) in the lives of students so that we can find appropriate solutions to help them during the process and also when we return to our normal activities. (AU)",2020,2021,Universidade Estadual de Campinas (UNICAMP),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C09819,20/07205-0,Evolution of computational infrastructure for storing and retrieving scientific health data,"The activities foreseen in this project will provide new computational functionalities for the storage and retrieval of scientific health data, as well as new interfaces for the visualization and analysis of data related to Covid-19. These data come from the Einstein, Sírio-Libanês and Fleury institutions, in a first moment, and public and other private institutions in a second moment. (AU)",2020,2021,Universidade de São Paulo,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Data Management and Data Sharing,,,Brazil,Brazil,Health Systems Research,Health information systems,2020 +C09820,20/10127-1,Development of vaccine against COVID-19,"After months of the worldwide spread of the SARS-CoV-2 coronavirus, it is clear that the development and production of a safe and effective vaccine is a promising public policy strategy to combat the pandemic, allowing the complete reopening of the economy and the prevention of new waves. epidemic. The Butantan Institute is a century-old institution dedicated to the development of biological medicines, being responsible for providing 65% of all vaccines and 100% of serums to the public health system in Brazil. Considering its qualification, self-sufficiency and ability to respond with agility to the specific health challenges of the population, the institute has attracted partnerships with the main developers of immunobiologicals in the world for the development and production of vaccines for COVID-19. The agreement signed between Instituto Butantan and Sinovac Biotech Ltd to carry out Phase III of clinical trials and subsequent production of the vaccine developed by the Chinese company is relevant due to the effectiveness demonstrated by the inactivated vaccine in Phases I and II and because it is a traditional and wide use. FAPESP, which has a recognized role in the production of knowledge and new technologies, is fundamental in the search for solutions to urgent issues. The relationship that will be established between Instituto Butantan and Fapesp to support activities that involve the development and regulation of the inactivated vaccine against COVID-19 goes towards the establishment of pandemic control and mitigation policies that impact health and social conditions and country's economic growth. (AU) The relationship that will be established between Instituto Butantan and Fapesp to support activities that involve the development and regulation of the inactivated vaccine against COVID-19 goes towards the establishment of pandemic control and mitigation policies that impact health and social conditions and country's economic growth. (AU) The relationship that will be established between Instituto Butantan and Fapesp to support activities that involve the development and regulation of the inactivated vaccine against COVID-19 goes towards the establishment of pandemic control and mitigation policies that impact health and social conditions and country's economic growth. (AU)",2020,2022,Secretaria da Saúde (São Paulo - Estado).,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +C09821,20/10710-9,EPICOVID 19-BR 2: national expanded access seroprevalence survey,"COVID-19 is a disease produced by the SARS-CoV-2 virus that is part of a broad family of viruses that can cause illness in humans and animals. This virus has spread rapidly around the world, which has led the World Health Organization to classify this disease as an international health emergency and, subsequently, to declare a COVID-19 pandemic. The number of cases reaches the figure of 19,200,000. cases reported in the world, but these data do not reflect the real prevalence of COVID-19 in the population, since they are susceptible to a series of limitations, given that people with more severe symptoms are more likely to perform the test, whereas asymptomatic individuals or those with mild illness have a low chance of undergoing the test. Brazil is the second most affected country, with more than 2,900,000 reported cases and 98,493 deaths. In Brazil, the State of São Paulo is the most affected state with more than 598,000 cases and 24,500 reported deaths. Therefore, to identify the magnitude of the problem, it is necessary to have data that allow a good estimate of the prevalence of the infection in the population, its dynamic behavior and the dispersion pattern of the disease in the various waves existing in the Brazilian population. Seroprevalence surveys are powerful tools for measuring the exposure of a given population to an epidemic infectious agent. The main objectives of this study are to estimate the seroprevalence of SARS-CoV-2 in Brazil, to evaluate symptoms and to analyze the speed of expansion of the infection in a territorial sample that covers a significant part of the Brazilian population. This study is part of and represents the continuation of the study EPICOVID 19-BR - Evolution of the prevalence of COVID-19 infection in Brazil: a population-based study, coordinated by the Federal University of Pelotas and with 6 sequential phases foreseen. However, for administrative reasons, the original funding foreseen for the study was interrupted after the completion of the third phase. At the moment, it was decided, also for financial administrative issues, to divide the sequence of the study into two parallel projects. 1) corresponds to phase 4 of the original study, with the same design and methodology and will be conducted by the same team from UFPEL with financial support from the institution Todos Pela Saúde, according to attached documents; 2) corresponds to the proposal presented in this project for funding in the form of Thematic Research Project, submitted to FAPESP. It will be conducted in a single phase, with a methodology similar to that of the original study, but with a significant methodological difference, which will be sampled all residents of the selected households. This will represent an approximately 4-fold increase in the sample size originally calculated. There are several advantages of this new design: 1) greater precision in prevalence estimates; 2) possibility of estimating differences in exposure by age and municipality / region with greater precision. Check more precisely the patterns of dispersion of the epidemic wave in the national territory; 3) finally, with the best epidemiological knowledge of the dynamics of the epidemic in our country, allowing the development of optimized control strategies. The following text describes the methodology of the original study with appropriate insertions and modifications for the description of the work that it proposes to finance through the FAPESP Theme. (AU)",2020,2021,Universidade Federal de São Paulo (UNIFESP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +C09822,20/05471-5,"Use of self-management strategies combined with multi-component training to mitigate the effects of COVID-19's social distance on functionality, physical capacity, mental health and quality of life for the elderly","Introduction: Considering the social distance (SD), recommended by the World Health Organization, due to the pandemic caused by Covid-19, and that the elderly population is considered a risk group, proposing recovery strategies for harmful effects resulting from the confinement period if make pertinent. Studies show that the use of self-management techniques and health education associated with regular physical activity reduces the pattern of physical inactivity and improves the physical capacity of the elderly. Objectives: i) to evaluate the effect of the period of confinement on the physical capacity of the elderly; ii) correlate changes in physical capacity resulting from the period of confinement with functionality, mental health and quality of life; iii) evaluate the association of multicomponent training with self-management techniques as an intervention method to recover functionality, physical capacity, mental health and quality of life after the confinement period. Methods: This is a blind, randomized and controlled clinical trial. Eighty elderly people will be divided into two groups: multicomponent training (Multi) (warm-up / aerobic, muscular endurance, balance and flexibility) and multicomponent training + self-management techniques (Multi + AG). The intervention will start immediately after the end of the confinement period and will last for 16 weeks. The assessment of physical capacity (handgrip strength, sit and stand test, timed up and go test, 6-minute walk test, unipodal support) will be performed before confinement (T0), immediately after returning to activities (T1) and after the intervention (T2). The measures of quality of life (WHOQUOL-OLD), mental health (GDS-15 and PSS-10) and functionality (WHODAS 2.0) will be performed in T1 and T2. Expected results: it is expected that the results obtained in the present study may guide future public health policies, aiming at recovering the possible deleterious effects arising from the period of confinement caused by epidemics and pandemics. (AU) aiming at recovering the possible deleterious effects arising from the period of confinement caused by epidemics and pandemics. (AU) aiming at recovering the possible deleterious effects arising from the period of confinement caused by epidemics and pandemics. (AU)",2020,2022,Universidade Federal de São Carlos (UFSCAR),,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09823,20/05539-9,Quantifications of COVID-19 radiological pulmonary structures (Coronavirus infection),"In December 2019, a series of cases were identified in China of the so-called COVID2019, which has spread throughout the world, currently reaching more than 2,000,000 cases with 140,000 deaths. Currently, viral nucleic acid analysis based on RT-PCR (real-time Polymerase Chain Reaction) is used as a standard reference method to confirm COVID-19 infection. One of the main consequences is a pulmonary inflammatory process, which leads to a large part of deaths and hospitalizations. In this sense, computed tomography (CT) is the method of choice for these analyzes and has been considered the main imaging method with high sensitivity for detecting the consequences of COVID19 and even considered as a diagnostic method. COVID19 causes several lung damage, mainly inflammatory processes that manifest themselves with ground-glass radiological findings, among others. The evaluation is subjective and requires trained specialists. Improvements in visualization and quantification of structures and radiological findings are essential for a better diagnosis and quantitative determination of the affected pulmonary percentage. In this proposal, using image processing, generate algorithms to enhance the affected lung characteristics and quantify these structures in relation to the lung volume. Methods of filtering, segmentation and extraction of objective characteristics in CT images will be used in the initial phases, during and after negative by RT-PCR, aiming at a temporal and spatial characterization, in front of the different pulmonary areas. This type of objective analysis will provide greater support for the diagnostic decisions of radiologists and clinicians, providing data support for the treatment and sequencing of cured patients and generating technological processes to aid diagnosis and support classificatory data involving pulmonary structures affected by COVID19. (AU)",2020,2022,Universidade Estadual Paulista (UNESP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Disease pathogenesis | Supportive care, processes of care and management",2020 +C09824,20/05212-0,The use of the face mask by the person with symptoms of infectious-contagious respiratory disease: the prevention of spread in public places,"Thousands of people worldwide die annually from respiratory diseases, with the elderly population being the most affected. According to the report by the Ministry of Health, in Brazil in 2019, 1,109 people died from influenza, with 54.6% of these deaths being patients over 60 years of age. Since the beginning of the year 2020, the world population has been alarmed by the fast and growing index of coronavirus infection (COVID -19) which has been responsible for infecting thousands of people around the world and causing more than 9,000 deaths. Today in Brazil (03/22/2020), according to the latest bulletin from the Ministry of Health, there are 1546 confirmed cases of COVID-19 in all states, the vast majority in São Paulo, with a record of 25 deaths and 3 in Rio de Janeiro. January. For the prevention of influenza, WHO recommends the adoption of pharmacological measures, such as vaccines; and non-pharmacological measures such as hygiene habits, (eg hand washing), isolation of the contaminated individual and the use of facial masks by health professionals. However, there are still no vaccines for the prevention of coronavirus (COVID-19) and the main WHO guidelines for preventing contamination are hygiene habits such as washing hands, covering mouth and nose when sneezing and social isolation. In Brazil, facial masks are recommended especially within hospital environments; and given the concern with prevention outside the hospital area, this project aims to address the use of facial masks, by people with symptoms of some respiratory disease, in public places as a preventive method against the spread of such diseases. Thus, the objective of this research will be to promote the population's awareness of the importance of preventing infectious and contagious respiratory diseases; understand the reasons for non-adherence or adherence to the use of the mask by sick people; and encourage the use of the mask as a measure of individual protection and non-propagation of respiratory diseases. The current research will be of a ""quanti-qualitative"" character, and will have Alfred Schütz's Social Phenomenology as a methodological framework for the analysis of qualitative data; demographic data of the quantitative part, analyzed with the aid of programs such as Excel and SPSS. The research will be carried out with the general and elderly population in a very busy corridor between the two Tatuapé train and subway stations, on the east side, in the city of São Paulo. As a result, we hope through the reasons that led them to wear masks or not, to be able to contribute to the prevention of respiratory diseases and to reduce the number of deaths mainly among the elderly population. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Infection prevention and control | Policies for public health, disease control & community resilience | Health Systems Research","Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Community engagement | Communication | Health service delivery | Medicines, vaccines & other technologies",2020 +C09825,20/06091-1,Analysis of genetic variants determinant for infection and evolution of the clinical picture in young adults with COVID-19,"The severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) has been causing a pandemic unprecedented in human history. In about 3.5 months of the disease (COVID-19), this virus has already infected more than 2.6 million people, causing more than 178 thousand deaths. Initially, it was believed that the prognosis of the disease would be poor almost exclusively for people in the so-called risk group (the elderly or people with pre-existing chronic diseases). However, we are seeing an increasing number of fatal cases in which the victims are young adults (<55 years of age) and apparently healthy. In the USA, the country most affected by the disease, people in this age group represent 51% of ICU admissions and, of these, S die as a result of the disease. Additionally, factors such as race and gender seem to have an importance in relation to the risk to COVID-19. Therefore, if analyzed from a broad point of view, such evidence suggests that there are genetic factors that determine the course of the infection and the response capacity of each organism to SARS-CoV-2. In this project, through DNA sequencing and computer analysis, we will study genetic variations in three groups of young adult patients infected with SARS-CoV-2: patients who have developed mild, severe or critical symptoms of the disease. In a first work front, we will look for genetic variations potentially associated with such symptoms. We will analyze variations in all coding genes and also in genes known to be involved in viral infection, such as ACE2 and TMPRSS2. On a second front, we will type the patients' HLA alleles and look for a relationship between these variations and a response (excessive or attenuated) to the virus. As a final result, we hope to identify a set of genetic variants associated with each group of patients. These results can contribute to predict individuals more (or less) vulnerable to the disease and to understand the molecular mechanisms of action of the virus, contributing to the development of treatments and effective ways to combat SARS-CoV-2. (AU) These results can contribute to predict individuals more (or less) vulnerable to the disease and to understand the molecular mechanisms of action of the virus, contributing to the development of treatments and effective ways to combat SARS-CoV-2. (AU) These results can contribute to predict individuals more (or less) vulnerable to the disease and to understand the molecular mechanisms of action of the virus, contributing to the development of treatments and effective ways to combat SARS-CoV-2. (AU)",2020,2022,Hospital Sírio-Libanês; Sociedade Beneficente de Senhoras (SBSHSL),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2020 +C09826,20/05984-2,Acute neurological manifestations associated with the SARS-CoV-2 virus,"In 2019, an outbreak of respiratory disease associated with a new coronavirus, SARS-CoV-2, began in the city of Wuhan, China. Since then, this highly transmissible virus has motivated extreme isolation measures around the world, in an attempt to mitigate the infection of entire populations, concomitantly saturating medical services and collapsing health systems. Several coronaviruses are associated with neurological syndromes such as encephalitis, myelitis and Guillain-Barré syndrome, among them SARS-CoV-1, phylogenetically the human coronavirus closest to SARS-CoV-2. Thus, it is expected that similar manifestations affect patients in the current epidemic. OBJECTIVES: To characterize the epidemiological, clinical, laboratory, electrophysiological and radiological profile of patients affected by myelitis, encephalitis and / or acute peripheral polyneuropathy in the presence of an epidemic associated with the SARS-Cov-2 virus. METHODS: This is a prospective observational study, which will assess the epidemiological, clinical, laboratory, electrophysiological and radiological characteristics of patients diagnosed with encephalitis, myelitis and / or acute peripheral polyneuropathy during the SARS-Cov-2 epidemic period, assisted in co-participant institutions. Patients who are considered to be suspected cases of SARS-CoV-2 will be selected according to criteria defined by the Ministry of Health (MS) and the World Health Organization (WHO) in the presence of proven community transmission, who present concomitant or subsequent clinical suspicion (up to 60 days after an event associated with SARS-CoV-2) of viral encephalitis, viral myelitis and / or acute peripheral polyneuropathy. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2020 +C09827,20/07200-9,Analyzing complex data linked to COVID-19 to support decision making and prognosis,"This supplementary research project aims to propose, explore and develop new methods and algorithms to be used in decision-making processes for medical diagnosis and prognosis of patients in the context of COVID-19. These methods and algorithms will be instantiated in systems and applications that will be made available to the scientific community to support this decision-making process quickly and accurately. The challenges to be overcome begin with the assembly of databases and images from different and often incomplete platforms, and the application of the radiomic technique on X-ray (RX) and computed tomography (CT) images, with the premise of whereas massive quantitative and qualitative characteristics on X-ray images can bring the necessary information to the diagnosis of COVID-19, in the same way that CT provides. The advantage of this approach that will be investigated is the lower cost and greater availability of X-rays, allowing more patients to benefit from the results of this proposal. In addition to providing cured and consistent material for research and advances in the area of ​​COVID-19. In addition, consistent databases and images for research will be made available to the community in the area. (AU)",2020,2022,Universidade de São Paulo,,Unspecified,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Data Management and Data Sharing,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Health Systems Research","Diagnostics | Supportive care, processes of care and management | Health service delivery",2020 +C09828,20/07069-0,Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19,"The current pandemic of the new respiratory disease Coronavirus 2019 (COVID-19) represents a state of international public emergency. The virus that causes the disease is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been circulating all over the world, triggering clinical manifestations ranging from asymptomatic cases to severe acute respiratory syndrome and death, especially of individuals with comorbidities (eg hypertension, diabetes and asthma). Thus, it is suggested the influence of immunological factors and other intrinsic factors of the host in controlling the development of the disease. Meanwhile, patients who develop severe illness may die due to intense immunodegulation. Yet, the knowledge about the systemic immunological mechanisms that control protection against SARS-CoV-2 is still scarce and the systemic response of CD4 + T lymphocytes, effector leukocytes and regulators of the immune system, remains to be characterized. The hypothesis of this project is that the T lymphocytes of patients with COVID-19 have a systemic exhaustion profile (defined by low effector function associated with high expression of inhibitory receptors). In other words, the T lymphocytes of patients who develop a more severe disease phenotype have an increase in the gene / protein interaction network associated with the exhaustion mechanism, influencing the severity of the disease phenotype. Thus, this project aims to characterize the mechanisms of exhaustion of the immune response of T lymphocytes in patients infected with SARS-Cov-2, with COVID-19 light and serious. We will carry out a systemic and integrative approach, investigating the CD4 + T lymphocyte transcriptome followed by specific functional assays for validating high-throughput screening (transcriptome analysis). In addition, we will perform a meta-analysis of data previously deposited in ArrayExpress and GEO (from English, Gene Expression Omnibus) to determine the networks of gene coexpression that systemically regulate the immune response to SARS-CoV-2. This large-scale experimental approach will allow us to define the immunological signatures, signaling pathways and networks of gene co-expression and the molecular (interactome) and metabolic (metabolome) interactions involved in the immune response against SARS-CoV-2. This way, it will promote a translational and multidisciplinary study that will be able to identify biomarkers for the differential diagnosis. This fact will pave the way for the development of new specific therapies that reduce mortality and morbidity induced by the virus. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity",2020 +C09829,20/06314-0,Acceptability of tele-rehabilitation as an alternative means of delivering physiotherapy programs in the context of COVID-19,"Introduction: Telehealth consists of using telecommunication means to deliver health services. As an arm of telehealth, telerehabilitation stands out in situations of social isolation imposed by both COVID-19 and geographical barriers as a viable alternative to expand access and allow the continuity and implementation of rehabilitation programs. Objectives: To observe the acceptability of the general population, patients and physiotherapists to tele-rehabilitation programs and to deepen the understanding of acceptability from the perspective of patients infected with SARS-CoV-2 (virus that causes COVID-19). Methods: The project will be developed from two studies: I) Cross-sectional study: an Online Survey structured on the TypeForms platform. Through open and closed questions, both patients and physiotherapists will be asked to give an opinion on items they consider necessary in tele-rehabilitation programs and also to provide information on acceptability in relation to this type of intervention. The sample will be for convenience. II) Qualitative study: samples for the convenience of patients who were infected with SARS-CoV-2 seeking to explore the concepts of acceptability, experience and telerehabilitation. Expected Results: It is expected that the acceptability of tele-rehabilitation is relevant and that the results obtained provide data for the planning and development of programs in tele-rehabilitation, contributing to the growing presence of technology in the health sphere and, consequently. (AU) samples for the convenience of patients who were infected with SARS-CoV-2 seeking to explore the concepts of acceptability, experience and telerehabilitation. Expected Results: It is expected that the acceptability of tele-rehabilitation is relevant and that the results obtained provide data for the planning and development of programs in tele-rehabilitation, contributing to the growing presence of technology in the health sphere and, consequently. (AU) samples for the convenience of patients who were infected with SARS-CoV-2 seeking to explore the concepts of acceptability, experience and telerehabilitation. Expected Results: It is expected that the acceptability of tele-rehabilitation is relevant and that the results obtained provide data for the planning and development of programs in tele-rehabilitation, contributing to the growing presence of technology in the health sphere and, consequently. (AU)",2020,2022,Universidade Cidade de São Paulo (UNICID).,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C09830,20/05949-2,"Fast, effective and low-cost molecular diagnosis of COVID-19 and strategies for large-scale population testing","The greatest success in controlling the pandemic triggered by the new coronavirus (SARS-CoV-2), called COVID-19, has been observed among countries with a great capacity to offer tests to the population, such as South Korea (Normile, 2020). However, with the growing need for inputs, often imported, for testing, countries capable of redirecting the domestic industry to produce their own inputs have managed to satisfactorily alleviate the demand for tests, as is the case of Germany, South Korea and Singapore (Editorial in Nature) (2020). However, most countries do not have the technological capacity to be self-sufficient in the production of tests, particularly the RT-qPCR test by TaqMan®, which is mostly used and recommended by the US CDC (Centers for Disease Control and Prevention) (Reusken et al., 2020). Thus, there is an urgent need to develop tests that use alternative inputs and that, ideally, are at the same time fast, efficient and of low cost. In Brazil, dependence on the import of inputs has been one of the main limitations for carrying out the diagnostic tests for COVID-19, as it at the same time delays and makes the process more expensive. In view of these limitations, our proposal is to develop a method based on molecular biology with the RT-LAMP methodology (reverse transcription loop-mediated isothermal amplification; RT-LAMP), which does not depend on sophisticated equipment and can be performed anywhere in the country, even in those with little infrastructure (Hong et al., 2004; Lamb et al., 2020; Shirato et al., 2014; Silva et al., 2019a; Zhang et al., 2020). In addition, we will produce the enzymes necessary for the test. We will also test the sensitivity of the test with pools of 5 to 20 samples together, which could make it possible to increase the screening of a large number of cases and identify population groups at higher risk. The development of these protocols will create technological knowledge for the development of rapid molecular diagnostic methods for the nationally produced COVID-19, easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop approaches to population screening that can guide the control of the SARS-CoV-2 epidemic. (AU) we will produce the enzymes necessary for the test. We will also test the sensitivity of the test with pools of 5 to 20 samples together, which could make it possible to increase the screening of a large number of cases and identify population groups at higher risk. The development of these protocols will create technological knowledge for the development of rapid molecular diagnostic methods for the nationally produced COVID-19, easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop approaches to population screening that can guide the control of the SARS-CoV-2 epidemic. (AU) we will produce the enzymes necessary for the test. We will also test the sensitivity of the test with pools of 5 to 20 samples together, which could make it possible to increase the screening of a large number of cases and identify population groups at higher risk. The development of these protocols will create technological knowledge for the development of rapid molecular diagnostic methods for the nationally produced COVID-19, easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop approaches to population screening that can guide the control of the SARS-CoV-2 epidemic. (AU) which may make it possible to increase the screening of a large number of cases and to identify population groups at greatest risk. The development of these protocols will create technological knowledge for the development of rapid molecular diagnostic methods for the nationally produced COVID-19, easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop approaches to population screening that can guide the control of the SARS-CoV-2 epidemic. (AU) which may make it possible to increase the screening of a large number of cases and to identify population groups at greatest risk. The development of these protocols will create technological knowledge for the development of rapid molecular diagnostic methods for the nationally produced COVID-19, easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop approaches to population screening that can guide the control of the SARS-CoV-2 epidemic. (AU) easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop population screening approaches that can guide the control of the SARS-CoV-2 epidemic. (AU) easily adaptable to other pathogens, thus contributing to the country's preparation to face similar crises in the future, as well as to develop population screening approaches that can guide the control of the SARS-CoV-2 epidemic. (AU)",2020,2022,Universidade de São Paulo,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09831,20/05293-0,Coronavirus infection (SARS-Cov2) in human cell models: search for therapeutic strategies,"The Center of Excellence in New Target Discovery (CENTD) is the result of a partnership between the Butantan Institute and the São Paulo Research Foundation (FAPESP) and the Pharmaceutical GlaxoSmithKline (GSK). It aims to identify and validate new molecular targets and signaling pathways involved in inflammatory diseases. For the identification of these molecular targets, poisons, toxins, molecules isolated from different animal secretions, as well as their peptide derivatives are being used. The discovery of new targets and their validation may allow the development of new drugs. There is a new public health crisis that threatens the world with the emergence and spread of the new coronavirus 2019 (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is mild in most people, but in the elderly and individuals with comorbidities, it can progress to pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The lethality rate currently stands at 4%. Treatment is essentially supportive. The role of antiviral agents has not yet been established. In view of the pandemic situation of the disease caused by SARS-CoV-2 and the competence developed by CENTD, throughout these years of its activity, our team in association with new collaborators from the Viral Biotechnology, Virology and Biopharmaceutical Laboratories of the Butantan Institute, Virology Laboratory of the Institute of Biomedical Sciences of the University of São Paulo and of the Institutes of Biotechnology / Molecular Biology and Experimental Medicine at CONICET, Argentina, intends to make efforts to contribute to a better understanding of this disease. Thus, this project aims to evaluate the inflammatory events triggered by SARS-CoV-2, in different cell models (pulmonary epithelial cells, endothelial cells and in human monocytes / macrophages), and their regulation by the use of molecules derived from animal secretions, potentially antiviral drugs, human monoclonal antibodies, as well as by mesenchymal stem cells. Such analysis will be carried out using a multidisciplinary approach that includes classic virology methods, cellular and molecular biology techniques and analyzes of immunological and pharmacological aspects. To identify the possible signaling pathways involved, additional approaches will be applied, including the use of specific pathway agonists or inhibitors.",2020,2022,Secretaria da Saúde (São Paulo - Estado).,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C09832,20/05288-6,The role of efferocytosis in tissue damage and hyperinflammation in SARS-CoV-2 infection,"Controlling the multiplication of the pathogen and tolerating the impact of the damage caused during the infectious process, are essential to ensure the survival of the organism. Macrophages are a determining component of innate immunity to infectious processes, not only for identifying and eliminating the invading pathogen and activating the immune system, but also for acting to control the inflammatory response and reduce immunopathology. In this context, macrophages are responsible for eliminating dead cells (process of eferocytosis) and orchestrating the mechanisms of tissue repair. Patients infected with SARS-CoV-2 who evolve to the critical form of COVID-19 have symptoms consistent with the development of a hyperinflammatory syndrome that can cause fatal injuries to different organs. However, these critical patients often have a low viral load, suggesting that a failure in the tolerance mechanisms that culminate in exacerbated immunopathology is preponderant in the critical cases of COVID-19. Recent studies describing the clinical aspects of COVID-19 point to the occurrence of exacerbated cell death during infection: patients have acute leukopenia, in addition to high levels of inflammatory cell death markers in the bloodstream. The hypothesis on which this proposal is based is that the excess of cell death during the infection by SARS-Cov-2 and a possible failure in the elimination of these cells contributes to the hyperinflammation observed in patients with severe manifestation of COVID-19. In this sense, we propose to determine the potential of phagocytic cells of patients with COVID-19 to eliminate dead cells, determining the importance of this process for hyperinflammation and its association with the severity of the disease. Finally, we propose to investigate the potential of a possible biomarker associated with the phagocytic activity of macrophages to discriminate the response to therapy with immunosuppressive and anti-inflammatory drugs in critically ill patients. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C09833,20/05451-4,COVID-19: selection of specific inhibitors for the main Mpro protease of SARS-CoV-2 through phage display,"The severe acute respiratory syndrome COVID-19 caused by the coronavirus SARS-CoV-2 is an emerging and highly contagious disease, with which the world is experiencing a pandemic from the end of 2019 to the present day, which has led several countries to bankruptcy public health service, and soon Brazil will be able to reach this situation. So far (04/13/2020) there are already at least 22300 people infected and 1230 deaths in the country. Worldwide, the number of deaths exceeds 116,000. The virus is advancing rapidly around the world, and everyone who can is looking for alternatives to contain it, so far we have no medicine, vaccine or other method of control other than social detachment. In order to contribute to this search for scientific knowledge for the development of specific anti-SARS-CoV-2 therapies, the molecular mechanisms that promote and sustain viral infection must be defined. An important therapeutic target among coronaviruses is the main protease Mpro (or 3CLpro), due to its essential role in the processing of polyproteins that are translated from viral RNA and enabling the formation of the viral particle. Thus, the purpose of this work is to identify specific inhibitors for the main Mpro protease of SARS-CoV-2 using the phage display technique using peptide libraries and protein inhibitors. (AU) the purpose of this work is to identify specific inhibitors for the main Mpro protease from SARS-CoV-2 using the phage display technique using peptide libraries and protein inhibitors. (AU) the purpose of this work is to identify specific inhibitors for the main Mpro protease from SARS-CoV-2 using the phage display technique using peptide libraries and protein inhibitors. (AU)",2020,2022,Universidade Federal de São Paulo (UNIFESP),,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C09834,20/05752-4,"Vitamin D supplementation in patients with COVID-19: randomized, double-blind, placebo-controlled clinical trial","100,000 IU on admission, followed by another 100,000 IU) after 5 days] or control (conventional treatment + placebo supplementation on the same days). Patients will be assessed for: 1) clinical and demographic characteristics (eg, sociodemographic data, comorbidities, medications for continuous use); 2) prognosis (eg, length of stay, number of cases admitted to Intensive Care Units, length of use of ventilators, number and severity of symptoms); 3) blood collection (eg, PCR for diagnosis of the virus and assessment of serum levels of 25-hydroxyvitamin D (25OHD), laboratory parameters included in the institutional guideline HC-FMUSP for the management of treatment of patients with COVID19 (eg PCR, D-dimer), calcium and creatinine (the last two, safety outcomes), on admission and on the day of discharge; 4) level of habitual physical activity (through a questionnaire). Demographic data and clinical characteristics of patients at the time of admission, as well as the patient's prognosis will be obtained through a specific questionnaire obtained from the HCFMUSP electronic medical record (Prontmed) or direct contact with family members and / or patients. Blood samples will be collected for laboratory analysis at the time of admission, and according to a routine hospital protocol. An aliquot will be stored for further analysis of 25OHD and biorepository, at the ward's hospitalization (day zero), day 7, day 14 and before discharge / death. The level of physical activity will be assessed only at the time of admission. This project has the potential to reveal, in an unprecedented way, whether vitamin D supplementation is safe and effective as an adjunctive treatment to COVID-19. In addition, the study will provide information, for the first time, about the influence of the level of physical activity on the prognosis of this disease. The findings may inform new clinical and public health measures to combat COVID-19 (AU) in an unprecedented way, if vitamin D supplementation is safe and effective as an adjuvant treatment to COVID-19. In addition, the study will provide information, for the first time, about the influence of the level of physical activity on the prognosis of this disease. The findings may inform new clinical and public health measures to combat COVID-19 (AU) in an unprecedented way, if vitamin D supplementation is safe and effective as an adjuvant treatment to COVID-19. In addition, the study will provide information, for the first time, about the influence of the level of physical activity on the prognosis of this disease. The findings may inform new clinical and public health measures to combat COVID-19 (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2020 +C09835,20/05527-0,Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury,"Our proposal will consist of the evaluation of the mechanisms of the disease in models of pulmonary comorbidities challenged with SARS-CoV-2 and protection induced by a vaccine using recombinant influenza virus expressing a segment of the Spike protein. Our hypothesis is that the pathology is largely triggered by an excessive activation of the innate immune response in the airway mucosa, and that with the development of the acquired response (IgA and cytotoxic T lymphocytes) induced by vaccination, the replication of the virus is minimized and the activation of cells of the innate immune system is attenuated. It is known that COVID-19 worsens in individuals with pulmonary comorbidities. However, it is not known whether this process involves a weakening of the immune response and an increase in viral load or just a worsening of the inflammatory reaction and, consequent increase in lung injury. As a model of comorbidities, we chose models widely used in our laboratories that trigger different pulmonary inflammatory response processes. Specifically, the models used will be infection models with fungus (Paracoccidioides brasiliensis, Pb), bacteria (Streptococcus pneumoniae, pneumococcus), viral (Influenza) and an asthma model, which induce chronic inflammation of the Th17 type and rich in neutrophils, a model of chronic pro-inflammatory inflammation rich in monocytes, acute pro-inflammatory response rich in monocytes and neutrophils and chronic Th2 response rich in eosinophils, respectively. In these models of comorbidities, different parameters will be evaluated, such as viral load, quality of the inflammatory infiltrate, activation of different pathways of the innate immune system, cytokine production and lung injury. These studies will focus on the toll-like receptors (TLR), inflammasomes and type I IFN pathways, using MyD88, ASC and type I IFN (IFNAR) deficient mice, respectively. Next, we will evaluate the capacity of the PR8 influenza virus, which is defective for multiplication because it does not express neuraminidase. In this virus, the extracellular region of neuroamindase is replaced by the RBD domain of the SARS-CoV-2 Spike protein. Studies carried out by our group have already demonstrated the ability of this neuraminidase-deficient virus to provide 100% protection for challenged animals. Therefore, we believe that we have a bivalent vaccine against influenza and SARS-CoV2. In addition, in previous studies we built an influenza virus that expresses the pneumococcal PspA protein and protects against co-infection with influenza and S. pneumumoniae, the major cause of lethality in patients with influenza and superinfected patients. Therefore, we will evaluate the degree of protection and immunological mechanisms involved in the viral load and inflammation of animals vaccinated and challenged with SARS-CoV-2, and in some groups, infected concomitantly with competent influenza-replication or pneumococcus. As for the protection mechanism induced by the vaccine, we will study the level of protection in mice deficient in B lymphocytes, CD8 + T lymphocytes and with combined immunodeficiency, using mutant mice for m chain, b2-microglobulin mice and RAG knockouts (KO) mice. Focus will be given to the role of neutralizing antibodies and IgA produced in the mucosa, as well as cellular response mediated by CD4 + Th1 and CD8 + cytotoxic lymphocytes. We believe that these studies will lead to a better understanding of the mechanisms of the disease and protection against influenza and SARS-CoV-2 viruses. (AU)",2020,2022,Universidade de São Paulo,,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2020 +C09836,20/05441-9,Impact on the mental health of the pandemic of the new Coronavirus (COVID-19) in the participants of the Longitudinal Study of Adult Health (ELSA-Brazil) of the state of São Paulo,"In late 2019, a new pathogen called SARS-CoV-2 (also referred to as ""COVID-19"" or ""new coronavirus"") was identified in Wuhan, China. The disease spread rapidly around the world, being characterized as a pandemic by the WHO in March 2020. Twenty percent of patients with this infection have severe or critical forms, particularly in those with advanced age or comorbidities. With the exponential increase in new cases and deaths associated with COVID-19, intensive quarantine measures were adopted. In Brazil, the state of São Paulo is the region that most registers cases of the disease and deaths, leading the government to decree quarantine across the state in the last week of March 2020. Faced with this scenario of social distance and home isolation, innumerable psychiatric and psychological repercussions can occur. In this context, we propose a prospective study to assess the psychiatric and psychological repercussions of the COVID-19 pandemic in the 4150 participants in the Longitudinal Study on Adult Health (ELSA-Brasil) followed at the São Paulo Research Center, in 4 evaluations to be carried out during the pandemic, online. The questionnaire will assess, using self-applicable scales, depressive and anxious symptoms, suicide, increased stress, protective factors and risk factors of this population during the COVID-19 pandemic. In addition, participants with self-rated mental health as ""poor"" will be invited to participate in a randomized clinical trial evaluating the effectiveness and safety of group vs. group psychotherapy. supervised group activities (""iPsico program""), via call center, in the reduction of depressive and anxious symptoms. Finally, we will provide psychiatric consultations online for participants with acute suicidal ideation or who refer to mental health as bad. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09837,20/06172-1,Counterproductive behaviors in coping with the SARS-CoV-2 pandemic in Brazil: investigation using a cohort of 10 years of follow-up and electronic Momentary assessment,"The SARS-CoV-2 pandemic requires several changes in the behavior of each individual in order to have a lesser impact on society as a whole. Thus, it is possible to identify individual behaviors that can aggravate the spread of the virus, called counterproductive behaviors. It is possible that individual aspects (such as temperament traits) and socio-environmental aspects (socioeconomic level, education, etc.) prior to the pandemic are associated with such behaviors, representing risk factors for greater vulnerability to contamination. However, it is very difficult to systematically assess the impact of these aspects, as longitudinal studies that have evaluated individuals previously and during the pandemic are necessary. The Projeto Conexão cohort (BHRCS) is in a privileged position to investigate risk factors for counterproductive behaviors. The study has followed 2,511 children and adolescents since 2010, when they were recruited from state public schools. After 3 and 6 years, the participants were reassessed with an extensive protocol on psychic symptoms, temperament traits and socioeconomic characteristics in an attempt to understand the developmental trajectories of mental disorders. Currently, international collaborations have allowed the research group to have access to a questionnaire that will be implemented in several cohorts around the world, via brief telephone interview and mobile application for intensive collection smartphone (Ecological Momentary Assessment). The questionnaire assesses aspects of COVID-19 infection and potential damage from the pandemic to mental health. The application allows to determine in an intensive way (4 times a day) if the individual is in open or closed places through the participant's report. The application also allows the sending of informational messages (push ups) on how to mitigate the harmful effects of the epidemic on mental health. Thus, the project will allow to empirically evaluate previous individual and socio-cultural aspects as risk or protective factors for counterproductive behaviors (eg breach of isolation) during the pandemic through time series associated with EMA. It will also be investigated, through regression discontinuity analysis, how messages impact on reports of psychic symptoms and counterproductive behavior in real time. Previous factors, such as temperament, will be assessed as moderators of the impact of informational messages on the participants' subsequent behavior. Therefore, the present project will allow a better understanding of aspects that lead to counterproductive behaviors, consequently increasing the risk of contamination and transmission of the virus. In view of the vast database already collected from the participants and the dynamism of the collection by the EMA, it will be possible to generate preliminary analyzes a few months after implementation, even in the epidemic period in the national context. (AU) will be assessed as moderators of the impact of informational messages on the participants' subsequent behavior. Therefore, the present project will allow a better understanding of aspects that lead to counterproductive behaviors, consequently increasing the risk of contamination and transmission of the virus. In view of the vast database already collected from the participants and the dynamism of the collection by the EMA, it will be possible to generate preliminary analyzes a few months after implementation, even in the epidemic period in the national context. (AU) will be assessed as moderators of the impact of informational messages on the participants' subsequent behavior. Therefore, the present project will allow a better understanding of aspects that lead to counterproductive behaviors, consequently increasing the risk of contamination and transmission of the virus. In view of the vast database already collected from the participants and the dynamism of the collection by the EMA, it will be possible to generate preliminary analyzes a few months after implementation, even in the epidemic period in the national context. (AU) In view of the vast database already collected from the participants and the dynamism of the collection by the EMA, it will be possible to generate preliminary analyzes a few months after implementation, even in the epidemic period in the national context. (AU) In view of the vast database already collected from the participants and the dynamism of the collection by the EMA, it will be possible to generate preliminary analyzes a few months after implementation, even in the epidemic period in the national context. (AU)",2020,2022,Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado).,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C09838,20/05207-6,Prospective evaluation of the production of lipid mediators in the immune response against COVID-19: search for biomarkers and new therapeutic targets in the evolution of the disease,"Due to the great spread of the new SARS-COV-2 coronavirus, we are experiencing a pandemic. COVID-19 disease, caused by this coronavirus, can have moderate to severe complications, especially in male, elderly and / or patients with underlying diseases. Severe cases present the ""cytokine storm"", with an exacerbated inflammatory response in the lung, the organ most affected. This project therefore seeks to identify molecular factors of susceptibility and resistance, as well as biomarkers of susceptibility and clinical evolution in COVID-19. To this end, we will investigate the inflammatory profile of patients by detecting and quantifying lipid mediators, including eicosanoids, steroid hormones and compounds derived from sphingolipids and ceramides, to look for a possible association with the clinical outcomes of COVID-19 and with components of the immune response, such as cytokines, chemokines and N-glycans profiles of IgG Ecs. In a case-control study approach, control participants (non-infected and asymptomatic) and patients treated at Hospital São Paulo in the city of Ribeirão Preto will be recruited, who will be evaluated clinically and laboratory by the doctors responsible for the care; proof of infection with SARS-COV-2 will be made in all participants. Plasma and leukocytes (buffy coat) will be obtained from the blood of participants. Protein inflammatory mediators will be quantified in plasma, as well as eicosanoids, steroid hormones, compounds derived from sphingolipids and ceramides. For this, through the use of mass spectrometry, we propose a multidisciplinary approach to identify lipid biomarkers related to the inflammatory process in COVID-19. The profiles of N-glycans in the Fcs of IgGs will be evaluated, according to the team's previous experience. The cells obtained will be frozen in Trizol, for further RNA extraction and analysis of gene expression. With these results, it is expected to understand in more detail, the pathophysiology of COVID-19, to establish markers of disease evolution and morbidity, as well as new targets for therapeutic interventions in patients infected with SARS-COV-2. (AU) The cells obtained will be frozen in Trizol, for further RNA extraction and analysis of gene expression. With these results, it is expected to understand in more detail, the pathophysiology of COVID-19, to establish markers of disease evolution and morbidity, as well as new targets for therapeutic interventions in patients infected with SARS-COV-2. (AU) The cells obtained will be frozen in Trizol, for further RNA extraction and analysis of gene expression. With these results, it is expected to understand in more detail, the pathophysiology of COVID-19, to establish markers of disease evolution and morbidity, as well as new targets for therapeutic interventions in patients infected with SARS-COV-2. (AU)",2020,2022,Universidade de São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C09839,19/18581-6,Development of colorimetric kits for porcine circovirus 2 (PCV-2) and SARS-CoV-2 quantification using gold nanoparticles,"Until the morning of March 31, 2020, 719,700 confirmed cases of SARS-Cov-2 were registered worldwide, causing a collapse in the health system of countries such as Italy, Iran and Spain. Brazil to date has recorded 4,661 confirmed cases, with 165 deaths. The transmission of the virus occurs mainly by contact with secretions and infected people, causing fever, cough, dyspnoea, myalgia or fatigue, sputum production, headache, hemoptysis and diarrhea. The diagnosis occurs after medical evaluation and laboratory tests such as RT-qPCR. However, these methodologies present as limitations a high cost for analysis of the samples, in addition to requiring specialized professionals and specific equipment. That's why, it is necessary to develop a new reliable and low cost methodology for a quick and simple diagnosis. Biosensors have stood out in the technological area as an analytical tool that can identify the presence of pathogens (antigens or nucleic acid) using nanoparticles as a base. Therefore, the objective of the present project is to develop and standardize colorimetric kits for the identification of both SARS-CoV-2 and viral RNA, using gold nanoparticles modified with the deposition of antibodies or specific probes, which, when attached to their respective target, will provide an immediate color change. This is a new technique that will promote a diagnosis in a quick, simple and low cost, in comparison with the usual methodologies. (AU) Biosensors have stood out in the technological area as an analytical tool that can identify the presence of pathogens (antigens or nucleic acid) using nanoparticles as a base. Therefore, the objective of the present project is to develop and standardize colorimetric kits for the identification of both SARS-CoV-2 and viral RNA, using gold nanoparticles modified with the deposition of antibodies or specific probes, which, when attached to their respective target, will provide an immediate color change. This is a new technique that will promote a diagnosis in a quick, simple and low cost, in comparison with the usual methodologies. (AU) Biosensors have stood out in the technological area as an analytical tool that can identify the presence of pathogens (antigens or nucleic acid) using nanoparticles as a base. Therefore, the objective of the present project is to develop and standardize colorimetric kits for the identification of both SARS-CoV-2 and viral RNA, using gold nanoparticles modified with the deposition of antibodies or specific probes, which, when attached to their respective target, will provide an immediate color change. This is a new technique that will promote a diagnosis in a quick, simple and low cost, in comparison with the usual methodologies. (AU) using gold nanoparticles modified with the deposition of antibodies or specific probes, which, when bound to their respective target, will provide an immediate change in color. This is a new technique that will promote a diagnosis in a quick, simple and low cost, in comparison with the usual methodologies. (AU) using gold nanoparticles modified with the deposition of antibodies or specific probes, which, when bound to their respective target, will provide an immediate change in color. This is a new technique that will promote a diagnosis in a quick, simple and low cost, in comparison with the usual methodologies. (AU)",2020,2022,Universidade Estadual Paulista (UNESP),,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09928,MR/V028391/1,AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment,"Our Vision is to shorten the time taken to identify safe, effective and affordable treatments for COVID-19. Our Mission is for AGILE to be the key link in the chain of accelerated drug development, evaluating potential candidate treatments for COVID-19 and advancing only the compounds most likely to be effective into large-scale clinical trials. Objectives include: 1. Establish a single UK-wide Phase I platform to accelerate the clinical evaluation of promising new treatments for COVID19, as a feeder programme for larger phase IIb/III trials 2. Implement a Bayesian adaptive platform design which can seamlessly evaluate the optimal dose, safety, tolerability and preliminary efficacy of potential COVID treatments, and flexibly match endpoints and study populations to drug action and anticipated deployment. 3. Develop a strong portfolio of promising compounds with potential for scalable deployment and affordable implementation, progressing at least 3 candidates for onward evaluation. 4. Work with the Department of Health to support Phase IIb/III trials in the UK, and to de-risk significant government investment in large-scale trials at a time when NHS resources are stretched beyond capacity.",2021,2023,University of Liverpool,2282448.11,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Therapeutic trial design,2021 +C09929,AH/V015877/1,Supporting Healthcare Professionals Through Covid-19: Understanding How Arts-based Methods Can Support Non-verbal Communication,"Effective, clear and compassionate verbal and non-verbal communication has been shown to be essential to good patient care, as well as part of an efficient and cost-effective healthcare system (McDonald, 2016). Since the Covid-19 outbreak, communication between patients and healthcare professionals has altered, with healthcare professionals facing new challenges: adapting to the introduction of widespread use of Personal Protective Equipment (PPE), video-call consultations, social distancing and limited physical touch. Healthcare professionals have described the impact of wearing PPE as isolating, exhausting and impeding communication, articulating the urgent need for research in this area which has been reiterated by proactive requests for support from institutions such as University College of London Hospitals (UCLH). Through Clod Ensemble's Performing Medicine programme WILLSON (Principal Investigator) provides sector-leading interventions in healthcare education using performative techniques from non-verbal artistic disciplines, such as dance and physical theatre, to enable healthcare professionals to gain a deeper understanding of how they communicate non-verbally. These techniques have been proven to enhance self-care and communication with patients and colleagues (Osman et al., 2018). This proposed research programme of interviews and workshops will investigate the impact of arts-based interventions on the training and support of healthcare professionals and medical students with regard to the non-verbal communication challenges presented by Covid-19. Undertaken by a unique, multidisciplinary partnership between arts organisations, NHS trusts and academics who have been collaborating for decades, this project will create, test, scale and disseminate online and in-person resources to support healthcare professionals and medical students.",2021,2022,Queen Mary University of London,280364.39,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2021 +C09930,AH/V015613/1,Far Apart UK: Looking beyond lockdown to understand how UK arts organisations can continue to support young people's wellbeing during COVID-19,"Extensive evidence confirms the positive impact of the arts on the mental health, wellbeing, capabilities and agency of young people, particularly those affected by multiple stress factors (including structural exclusions caused by poverty, race, religion, gender and sexuality, cognitive and physical ability). Participatory arts programmes promote positive mental health alongside supporting young people to learn and practice their rights and responsibilities as they become critical citizens. Research shows that pandemics can trigger mental distress (including depression and anxiety) particularly in young people. The COVID-19 pandemic has created an urgent problem for young people, especially those made more vulnerable by intersecting challenges such as poor mental health, low educational achievement and social exclusion (including racism). The COVID-19 pandemic and resulting social distancing measures forced arts organisations to move their activities online, changing the ways in which they support vulnerable young people. This study investigates how arts organisations continue to re-invent their programmes to support young people during the pandemic, examining the impact of these changes on arts workers and how young people are experiencing this new way of connecting with their peers and communities. Research questions: 1. What are the consequences of lockdown and social distancing measures on how arts organisations support the development of young people (18-25)? 2. What are the critical challenges arts organisations are facing in transitioning from physical to digital and other social distancing measures? What can they learn from this experience? 3. How are young people coping with the emergency situation and what role can the arts play in building resilience?",2021,2021,Queen Mary University of London,397790.2,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09931,AH/V015478/1,Visitor Interaction and Machine Curation in the Virtual Liverpool Biennial,"This project looks at how audiences interact with machine-curated virtual exhibitions, specifically in the context of the 2020-2021 Virtual Liverpool Biennial. Using machine learning technologies as curators (rather than as, say, search engines) could potentially change the landscape of online exhibitions, which are currently largely websites with some pictures of artworks (and thus look more like exhibition catalogues than the exhibitions themselves). The project will look in particular at how different types of audience (e.g. local Liverpool residents who might not visit other biennials, vs people in the international contemporary arts scene who do the whole ""biennial circuit"") interact and engage with the co-curated virtual biennial: looking especially at how their curatorial choices or preferences might differ. Finally, the project will look at the link between virtual exhibitions and the physical event; and point towards possible new hybrid (online and physical) models for biennials and other art exhibitions.",2021,2021,Durham University,108167.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C09932,AH/V015443/1,Digital footprints and search pathways: working with National Collections in Scotland during Covid19 lockdown to design future online provision,"The COVID-19 pandemic is affecting every aspect of daily life, including the human need to connect to collections held at museums and galleries. The timing of the pandemic has been particularly damaging for Scotland's 409 museums and galleries. A clear understanding of how people access national collections online can make cultural institutions better prepared for digital service provisions in general, and especially for a crisis situation should there be another lockdown for COVID-19 or a similar catastrophe. This project will undertake a longitudinal study of the digital footprints of users in two national collections - National Museums of Scotland and National Galleries of Scotland - over a 12-month period to investigate: how people engaged with heritage collections during the lockdown and post-lockdown period; whether the lockdown changed digital access patterns; which collections/objects drew more users; and where users are accessing these, for example, through the institutions' websites, or through external platforms like Google Arts and Culture, Youtube, etc. This will lead to a short term impact by informing future policy decisions on the most effective digital platforms for national collections, and how the knowledge of online access patterns can be used to design search pathways that can lead to an ontology-based approach to linking collections combining the user search terms and semantics-based representations of the collections/items accessed. This can make a long term contribution to heritage collection data standards, particularly what data is recorded at object level, something similar to what CETAF (cetaf.org) is achieving for natural history specimens.",2021,2022,University of Strathclyde,222413.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C09933,AH/V015273/1,"Bereavement rituals during the Covid-19 pandemic: Implications for mental health support, funerary practices and public health messaging","Rituals around death and dying allow 'healthy' expression of strong emotions, with funerals identified as a fulcrum in the grieving process. The Covid-19 pandemic has dislocated these significant rituals. Their absence is likely to disrupt 'normal' grief cycles, leading to a range of complex grief presentations. Evidence from prior infectious diseases (Ebola, SARs, MERs) highlighted that some individuals will subvert public health messages to deliver rituals perceived essential to their relative's care and burial. Anecdotal evidence suggests that these behaviours are being mirrored in the Covid-19 pandemic. We will carry out a qualitative research programme to: identify the nature and extent of mental health support necessary following Covid-19, understand the experience of subverting or adhering to public health messages, and assess how public health messages could be developed to support the bereaved in managing the funeral process (e.g. development of replacement rituals) when social distancing is essential. We will carry out qualitative interviews at two time points (six months apart) with 30 bereaved families to explore the short and longer-term impacts of bereavement during the pandemic on mental health and wellbeing. In addition, we will conduct 30 interviews with funeral directors to understand their experiences of the funeral planning process during the pandemic, change in services and their interactions with bereaved people. Along with interim, final reports and peer reviewed open access papers, we will carry out a 'lessons learnt workshop'. This will develop recommendations about funerary arrangements, bereavement support provision and public health messaging, developing and agreeing industry-specific requirements.",2021,2022,NatCen Social Research,162044.81,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C09934,AH/V015230/1,Outside the box: open-air performance as a pandemic response,"COVID-19 has introduced enduring challenges to arts and culture organisations, demanding innovation in response to public health guidelines. Yet there has been little discussion of the range of practices and sites being used for performance beyond theatre buildings, and the practicability of socially-distanced, live, in-person assembly for outdoor arts, especially in public spaces. This inter-disciplinary project between drama and management studies comprises two strands. The project will work with civic partners to identify how public spaces may be used for performance, harnessing the revivified community engagement with green spaces beyond the home, brought about by the lockdown and aligned with the national aspiration for transformation, to Build Back Better from the pandemic. While open-air performance has been a first stage in cultural re-opening, merely replicating indoor models outside does not resolve key safety and management issues. Hence, the first strand aims to document the nature and extent of innovative outdoor practices across the UK, and understand the management challenges from the perspective of two sets of principal stakeholders: artists and local government. Drawing on models of site-specific, dispersed, threshold, and ecological performances, alongside practice-as-research with artists who have long-term experience and expertise in these genres, the second strand entails a season of commissioned practice-as-research work in 2021. The festival of work will make these innovative models more visible and contribute to the revival of live performance cultures UK-wide, providing exemplars of sustainable cultural practices and assisting local government to facilitate culture for quality of life in a physically-distanced world.",2021,2021,University of Exeter,186825.73,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09935,AH/V015206/1,VIP-CLEAR: Voices in a Pandemic: Children's Lockdown Experiences Applied to Recovery,"Our proposal explores how the COVID-19 pandemic has impacted the learning, development, health and wellbeing of vulnerable, socially-disadvantaged children (Early Years: 3-5yrs; Primary: 5-11yrs) in England by capturing their voices and experiences. Their families live with multiple uncertainties, stresses and vulnerabilities, making these children more susceptible to COVID-19 impacts and highlighting deep societal inequalities. Our interdisciplinary research aims to: 1) gather and critically evaluate the worldviews, perceptions and experiences of socially-disadvantaged children during the COVID-19 response; 2) draw learning from the above to support their involvement in 'recovery'; 3) build anticipatory resilient capital from their experiences in preparation for future social shocks, including pandemics. We focus on multicultural Bristol, where we have well-established relationships with practitioners/stakeholders in children's learning, health and wellbeing. This will ensure meaningful co-production with local, regional and national partners (nursery centres, schools, Bristol City Council and Action for Children) for immediate translation of our findings in policy and practice at different scales. Our approach gathers and exchanges critical 'data' quickly: using creative, participatory 'daylighting' methodologies that are child-focused and multi-channel. Our methods interweave socially-engaged arts practice with social science to capture nuances and trends in children's voices and ensure their views are included. We will co-develop outputs tailored to different stakeholder needs: a unique archive of children's voices to inform recovery strategies; a primary school book to support children and professionals; and an extensive evidence-base to inform policy and practice around adaptation to future social and ecological shocks.",2021,2022,University of the West of England,330918.69,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C09936,AH/V015192/1,Nature's Way: Co-Creating Methods for Innovating Nature-based Solutions for Public Health and Green Recovery in a Post-COVID World,"This project aims to co-create Nature-based Solutions (NBS) knowledge to empower communities, organisations, and individuals to innovate NBS as alternatives for healthcare and societal resilience following the COVID-19 pandemic. It will take a human-centred design approach to enable wider collaboration and to integrate otherwise 'siloed' knowledge and expertise. This project is a joint-effort between the Royal College of Art, the University of Sheffield, Walsall Housing Group, Bradford City Council, Shared Assets, HAS technology, National Association of Voluntary and Community Action, and Intelligent Health. NBS are actions, e.g. ecological restoration, that work with nature to help address societal challenges. In this proposal, it refers to social innovation actions utilising green space, parks and lakes, for the purpose of health and wellbeing. It is based on the evidence that regular contact with nature enhances physical health and mental wellbeing, and creates social benefits. It expands the concept of 'green prescription' to include wider communities and public beyond patients and GPs. The main deliverables of the project are: - An integrated method supported with training webinars enabling people to innovate and improve cost-effective NBS; - An open innovation platform facilitating NBS development using the integrated method, to link available resources and different stakeholders including commissioners, providers, agencies and voluntary community action groups and individuals; - The outcome of the pilots - NBS concepts - will be implemented by Walsall Housing Group and Bradford City Council to create immediate benefit to vulnerable people in these two areas, building upon existing approaches in the creation of service directories; - One journal paper, two conference papers to examine the role of design thinking in NBS innovation.",2021,2022,Royal College of Art,449569.09,Human Populations,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C09937,AH/V015176/1,"The New Real - Trust And Acceptance In Networked, Online Experiences To Enable And Support Post-COVID19 Recovery","The vast majority of cultural organisations face significant barriers in transitioning towards networked, online cultural and business models. We call this the 'New Real.' New literacies and skills are needed to develop and delight online audiences while negotiating the profound, complex challenges surrounding safety, privacy, transparency, and misinformation in networked environments. Being able to critically reason about the function of a system makes us more resilient in the face of future system failures, or can help us to make judgements about whether systems are safe and ethical. Our project responds directly to this need. Qualitative research through participatory design and ethnographic methodology will investigate the potential for strategies from data arts to be tailored and situated for organisations newly producing online experiences. It will specifically address the design of online and hybrid experiences to both delight audiences and develop critical literacies around the underlying tensions and moral dilemmas in the New Real. Aim: to better understand how to facilitate and accelerate the transition to resilience through new cultural, social and economic models for the UK's world leading cultural sector. This is supported by three concrete Objectives (O), each corresponding to a work-package (WP) and research question (RQ): O1: Understand the strategies used by data arts practitioners and organisations to delight audiences and build critical literacies in the New Real. O2: Co-design pathways with cultural organisations towards new forms of pandemic-resilient online and hybrid experiences. O3: Synthesise a set of actionable insights, tools, concepts and models that can enable and support post-COVID19 recovery.",2021,2022,University of Edinburgh,520246.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C09938,AH/V015168/1,COJO for COVID recovery: Solutions-focused constructive journalism as a pandemic exit strategy for local/regional UK communities,"This project uses COVID-19 as the research situation to investigate - through a UK-wide rollout - the potential power of the novel genre of solutions-focused constructive journalism (known as COJO) in helping local/regional communities to deal with unprecedented challenges. As the public emerges out of the lockdown to face a painful and uncertain struggle to exit from the pandemic, they will need to be informed, inspired and empowered to respond to social problems in a forward-looking manner. As a rigorous evidence-based reporting framework and toolkit that shifts the focus from what is the problem to what is the solution, COJO - also called solutions journalism (SOJO) - holds a strong potential to serve that acute cause. Gathering Bournemouth University, the Association of British Science Writers, the Solutions Journalism Network and Newsquest, this project investigates the extent to which and the way in which COJO can help the UK public to transition to the ""new normal"". It entails three major activities over 18 months: (a) investigate what a pandemic-wounded public expects the media, especially local news, to do to help them out of the crisis in an informed, inspired and forward-looking manner; (b) use the findings and insights from the first phase to develop and deliver a learning-by-doing campaign in which local news titles across the UK produce constructive journalism on COVID-19 solutions; and (c) evaluate the overall values of constructive journalism for both the news industry and the public during the exit and their implications for news coverage of future epidemics/pandemics and crises.",2021,2022,Bournemouth University,390117.4,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2020 +C09939,AH/V01515X/1,"Walking Publics/Walking Arts: walking, wellbeing and community during Covid-19","There is a proven evidence base for the benefits of both walking and art on physical health and mental wellbeing. Our project addresses the lacuna between the arts and those working to promote walking well in the wider community. Walking organisations need rapidly to find new ways to support their members during social restrictions, and to diversify membership to support more people to walk well in and beyond a pandemic. COVID-19 poses an unprecedented challenge to cultural organisations with the need to rethink practices due to physical distancing. Responses to lockdown have created the opportunity to understand how creative walking activities have been and could be used to mitigate isolation and anxiety, maintain health and wellbeing, enhance social connectivity, and facilitate cultural empowerment. This project will deliver a significant contribution to the understanding of, and response to, the COVID-19 pandemic and its impacts, generate new data about a key activity, and innovate arts resources for rapid implementation to support health, wellbeing, resilience and cultural participation. Collaborating with partner organisations, artists, cultural workers, and residents, the project will capture: a) the walking experiences and creative interventions of people during COVID-19 restrictions. b) the 'lockdown' work of artists using walking activity within conditions of restriction. c) the potential of the arts to sustain, encourage and more equitably support walking during and recovering from a pandemic. Key deliverables include: i) a new data set and report on walking experiences and creative approaches to walking well and safely ii) a curated digital gallery of creative walking models, open-access Walking Toolkits and piloted prototypes iii) a Cultural Walking Summit iv) three peer-reviewed articles v) a new cross-sectoral partnership.",2021,2022,University of Glasgow,400624.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C09940,AH/V015125/1,Coronavirus Discourses: Linguistic Evidence For Effective Public Health Messaging,"Developed in partnership with Public Health England, Public Health Wales and NHS Education for Scotland, this bid addresses key challenges that the coronavirus pandemic presents in relation to understanding the flow and impact of public health messages as reflected in public and private discourses. Our collaborators above who are charged with constructing effective public health messages have identified two particular challenges: messaging around geographical borders (e.g. between England and Wales, and in local lockdowns) and messaging aimed at BAME populations. These areas will be the focus of our research, and we will deliver benefits to our collaborators in the form of initial analytical results and discussion from month 2 onwards. As human behaviour is shaped by the reception and production of discourse, and by the reasoning about different sources of information, we propose a new approach to track the trajectories of public health messages once they are released to the public. Moving beyond corpus linguistic approaches that focus on language production, we will investigate the complex relationship between the production and the reception of discourses relating to specific types of public health messages, focusing on linguistic patterns (in particular modality and stance markers). Drawing on our track record in the construction and analysis of heterogenous corpora and our ongoing work on privacy enhancing technologies, we propose to carry out the first large scale analysis of the trajectories of public health messages relating to the coronavirus pandemic in the UK.",2021,2022,University of Nottingham,507525.14,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2021 +C09941,AH/V015109/1,"Local food-growing initiatives respond to the Covid-19 crisis: enhancing well-being, building community for better futures","The Covid-19 crisis has revealed the stark inequalities in UK society. Many vulnerable people have had more difficulty accessing food, so third-sector organisations have mobilised emergency food provision. They have also expanded community food-growing initiatives, which enhance participants' well-being, strengthen social cohesion, localise food provision and thus build future resilience. This project will investigate the expansion of community cultivation during the Covid- 19 crisis, its benefits, social barriers and means to overcome them, especially for more vulnerable marginalised social groups, with the aim to strengthen third-sector capacities for such inclusion. Through participatory digital story-telling, this project will work with third-sector partners in community cultivation to elicit participants' feelings, aspirations, social connections and multiple benefits from community food activities. This knowledge will identify the most effective strategies that have been deployed during the Covid-19 crisis, and devise ways to share and promote them. Thus the digital story-telling process has a dual purpose: a research method and a means to promote better practices through our third-sector partners. As a practical impact, food growing activities will strengthen their engagement with vulnerable marginalised people, thus helping to overcome inequalities. Based on the digital assets and research insights, the project will provide an open-access online capacity-building programme for community food programmes, so that they can outscale similar benefits around the country. This impacts will promote better mental health, well-being and better access to healthy food; they will also spread agri-food practices that enhance social resilience, and thus provide an alternative to the unhealthy, unsustainable agrifood system.",2021,2022,Open University,89603.57,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Other secondary impacts | Community engagement,2020 +C09942,AH/V015060/1,Covid in Cartoons: Empowering a thick narrative of the crisis by promoting cultural literacy and diversity skills amongst vulnerable young people,"Covid19 poses specific challenges for young people from vulnerable or minority groups, who may feel particularly disempowered by the pandemic (Wilton 2020). In order to restore their sense of agency and belonging, schools will not only need to remedy curriculum and attainment gaps, but also to create an inclusive framework that recognises the differential impact and lived experiences of the crisis, with a view to rebuilding social cohesion. Research shows that engagement with minority narratives is key to ensuring a cohesive processing of traumatic experiences and to avoiding competing memories that might underpin long-term divides and dynamics of victimisation. The project hence aims to foster a 'thick' cultural narrative, including diverse, contextualised views of the crisis and the future. We will do this by promoting processes of meaning-making amongst 15 to 18 year-olds from disadvantaged backgrounds, as this group faces challenging educational transitions. An online minicourse, delivered in collaboration with Shout Out UK, an award-winning educational platform, and Cartooning for Peace, an international network of cartoonists, will use political cartooning on the pandemic to engage participants with representational strategies, varying critical perspectives and humour to build their cultural literacy and diversity skills. By helping them to come to terms with their own as well as other experiences, the project will generate increased criticality, ownership and pathways of resilience. Academic publications will map processes of cultural meaning-making and strategies for an inclusive social response and curriculum. An online anthology and end-of-project film and report will ensure broad dissemination of results.",2021,2022,University of Leicester,412729.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Minority communities unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement,2021 +C09943,AH/V015052/1,"Distanced Arts: Investigating the design, delivery, and impacts of Entelechy Arts' Staying Connected Programme","On-going concerns related to the coronavirus pandemic (severe illness, changing distancing restrictions, second-wave of pandemic) present an increased risk for social isolation (reduced contact friends and/or family; loss of relationships, exclusion from society), which can have a disproportionately negative impact on health and well-being particularly among older adults. Given the uncertainty around the course of the pandemic, remote solutions that help older adults to stay connected are needed. In collaboration with Entelechy Arts, this project will consider one such solution, a distanced arts intervention - Staying Connected - from the perspective of service providers and users. Across two work packages (WP) we will use semi-structured interviews to understand service providers' (staff, artists, volunteers) experiences of distanced arts design and delivery (n=15; WP1), and conduct a longitudinal quantitative survey (2 time-points over 6 months) assessing whether there are changes in participants' isolation, health, and well-being as a results of taking part in Staying Connected's programmes (remote radio show (n=30), creative activity boxes (n=30), choir (n=16), and other activity clusters (knitting, poetry; n=10); WP2). Deliverables and outputs include a practice report outlining guidelines and recommendations for service providers who seek to design and deliver distanced arts, a virtual workshop to share the learning about practice with relevant stakeholders (arts organisations, councils, community members, government), an impact report detailing the effects of Staying Connected programme's on older adults' isolation, health and well-being, a virtual dissemination event to share the impact findings with relevant stakeholders, and two manuscripts for publication in high-impact academic journals.",2021,2022,Queen Mary University of London,271204.29,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Volunteers | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C09944,AH/V015001/1,Information Design for Diagnostics: Ensuring Confidence and Accuracy for Home Sampling and Home Testing,"n this inter-disciplinary project, information designers are working with diagnostic technology researchers on the design of procedural instructions and information to accompany home testing and home sampling kits. COVID-19 testing has placed an unprecedented burden on diagnostics services and sample collection remains a major bottleneck. Samples taken at home can be sent to labs, avoiding the need for sample collection at a clinic or hospital. Point-of-care testing technology can also allow testing in the home, without requiring a diagnostic lab. In both home sampling and home testing, simplicity and accuracy is critical to compliance. We will design spoken and written instructions for home sampling - where fingerstick blood is sent to central labs for testing; and for home testing using conventional lateral flow rapid tests. Information design methods, including evaluation of effectivenesss with a cohort of volunteers will ensure that the needs of users are met. We will combine established information design principles with novel methodology exploiting videolink research plus 3D printed models of home testing equipment to develop a complete set of guidance for a wide range of home diagnostics. By contributing to the success and viability of mass home testing, our work will have economic, social and health impact and unburden health centres with people that need to physically attend for testing.",2021,2021,University of Reading,144646.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C09945,AH/V014986/1,"Routes of infection, routes to safety: Creative mapping of human-viral behaviours on the bus to understand infection prevention practices","There is an absence of qualitative, interdisciplinary research on the personal application of infection prevention (IP) measures, like hand-washing and mask-wearing, and its effectiveness beyond the healthcare setting. In this crisis, IP measures are critical to building confidence to resume leisure and economic activity out of the home. The project advances previous work by this team that identified a need for novel IP research which integrates behavioural, microbiological and aesthetic approaches to creatively demonstrate the interactions of human movement with microbial/viral transmission. The case study is the public transport bus and its diverse community of users, including BAME and other higher-risk groups. The research will: i) investigate the structural challenges in consistent application of IP in public (and private) spaces; ii) provide microbiological and sociological evidence to inform and improve effective cleaning practices for bus operators and safe travel practices for bus users; iii) generate wider public knowledge and understanding of infection risk/prevention and their geographies in shared indoor spaces. This project will build confidence by addressing unknowns about the potential viral threat of boarding the bus. The team will work quickly to undertake and integrate findings from an ethnographic research and a microbiome study to assess the effectiveness of bus cleaning routines and passenger PPE. A fluorescents mapping simulation using ultraviolet powders and sprays will mimic and demonstrate visually the mobility of 'mock' SARS-CoV-2 through contact and aerosols if IP measures are not implemented. Outputs include the creation of novel viral aesthetic materials to communicate the effectiveness of IP.",2021,2022,University of Southampton,235137.96,Human Populations,Asian | Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience","Barriers, PPE, environmental, animal and vector control measures | Communication",2021 +C09946,AH/V014943/1,At Home with Children: Liveable Space for the COVID-19 challenge,"This study focuses on the uneven psychological and social impact of the pandemic on children, young people and their families through the hidden-in-plain-sight factor of physical domestic space. Many studies challenge the idea of home as a 'haven', arguing that domestic space is also a place of family conflict and negotiation. This challenge has been exacerbated by COVID-19. As a pattern of epidemic ebb and flow becomes a potential long-term reality, increased density of occupation over time and disrupted home-life norms will see the 'liveability' of dwellings for children and their families stretched beyond original capacities, affecting mental health, productivity and well-being. Informed by a nationwide survey and experiential accounts of child and adult family members, this research explores inter-relationships between social experience, psychological well-being and everyday domestic space. With a focus on the liveability of dwellings set against complex home/school/work conditions, the study also captures spatial forms of resilience that have emerged in response to COVID-19, to better support families' social and psychological well-being. These inventive responses will be synthesised through a co-design process, leading to an evidence-based 'Home-Hack Toolkit' for widespread dissemination directly to families. The broader findings will inform urgent policy-making that better supports those at risk of the pandemic's psychological and social impacts, by identifying the domestic settings and socio-spatial scenarios that present the greatest challenges to families. For longer-term structural impact, the data will also permit testing of UK domestic space standards, creating a crucial resource to inform liveable dwellings for a contemporary 'pandemic-ready' context.",2021,2022,Newcastle University,606247.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09947,AH/V014870/1,Brain Waves: Accessing creative cultural activity for people living with brain injury through and beyond the Covid-19 pandemic.,"Brain Waves will investigate the impact of the radical shift in the delivery of creative cultural activities for people living with brain injury during Covid-19 pandemic/lockdown and also the ongoing, and likely long-lived, changes in social interactions. We aim to move towards online/digital delivery, and to incorporate social distancing. In particular it will focus on the needs of two cohorts of people: 1. Patients recently discharged from hospital who, especially in the current context when community teams are less able to visit homes, fall between the cracks in terms of support. 2. People who access arts interventions as an essential part of their healthcare and recovery pathway and for whom self-expression through the arts is a key aspect of their reimagined identity and wellbeing. It builds on the ground breaking work of Rosetta Life and partners through the Stroke Odysseys project, which itself is beginning the journey towards a delivery structure blending digital/online resources and face-to-face social distancing sessions and expands the benefits to other brain injuries including Parkinson's Disease, Dementia, Multiple Sclerosis and Motor Neuron Disease. The work will have peoples' voices at the heart of the enquiry: people living with brain injury, healthcare professionals and artists involved in their care, and volunteer Ambassadors (that is, people living with brain injury who have already engaged in Rosetta Life's work and who want to offer peer support for people beginning their journey of rebuilding their lives post brain injury). The project team brings together academics from a range of disciplines at King's College London, community investigators with expertise in performance, arts, healthcare and community engagement, and community partners (see below). We will ask the following research questions: What is the impact of digital and socially distanced engagement in creative cultural activities on the wellbeing of people living with brain injury? And how do these impacts compare with current live face-to-face engagement? What are the benefits/opportunities here for the people who can access this online but wouldn't otherwise be able to, and how can they be reached? How do we build community participation remotely, online and/or with social distancing in place? And how might this influence cultural programming? Do we need to rethink 'community' in general given the major shift to 'online'? Are there downsides i.e. can online sessions actually end up reinforcing loneliness the second they end and the participants alone again? Is it feasible to upscale this participatory work via online resources? And if not, what is needed to support online delivery in socially distanced cultural programming? And how might these resources support the role of the socially engaged artist? We will deliver: An arts intervention that supports access to and engagement in creative cultural activities for at least 20 people living with brain injury - some of the most vulnerable and isolated people in our communities A collaborative, key stakeholders partnership in the area of Kings Health Partners supporting the wellbeing of people living with brain injury A set of online education training resources and a framework for artists, healthcare practitioners and the wider voluntary sector in order to test the potential for upscaling through socially distanced and online forums. A research report publishing findings and the implications for arts, healthcare and community engagement practice A conference event which draws together the key people and learning, made available across the UK via live streaming and recording.",2021,2022,King's College London,463691.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2020 +C09948,AH/V014781/1,Fraud During a Pandemic: Identifying and Appraising New Challenges for the Criminal Justice Response in England and Wales,"The global Covid-19 pandemic has presented new opportunities for those looking to commit fraud, capitalising on new vulnerabilities (of systems, organisations, and members of the population), propelled by sophisticated cyber-enabled schemes. There has been an increase in fraud during the pandemic, as well as an increase in its complexity, which places it front-forward as a criminal law issue which requires advanced analysis. For example, on 7 May 2020, Action Fraud reported that a total of £2,996,252 has been lost by 1467 victims of coronavirus-related scams. 6069 reports of coronavirus-related phishing e-mails were received. Penalising fraud, especially against vulnerable members of the population such as older persons, has been held to be an 'immediate' charging priority for the Crown Prosecution Service. A number of public bodies--the National Crime Agency, the National Economic Crime Centre (NECC), the Cabinet Office--have current interests in fraud research during the time of Covid-19. This research project has two aims. First, it will map the landscape of how fraudulent conduct is changing during the pandemic. This will be achieved in collaboration with the Crown Prosecution Service (CPS) and a series of roundtable discussions with fraud policy-makers and practitioners. Secondly, by critically appraising semi-structured interviews with leading fraud practitioners, it will provide a normative framework for how emerging dishonest conduct ought to be charged and prosecuted at this time. The project will lead to two major academic articles on fraud during a pandemic (a theory piece and a governance piece), and a policy paper on fraud governance.",2021,2022,University of Bristol,44297.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C09949,AH/V014730/1,"Downloading a new normal - privacy, exclusion, and information behaviour in public library digital services use during COVID","The necessity to switch from analogue to digital in so much day-to-day living has been the overarching experience of the COVID lockdown for many of the UK population. This project explores ""the digital turn"" and how compelled use of digital services during COVID lockdown and beyond has impacted one specific sector, namely public libraries across the UK. In doing so it considers issues that have been faced in other public and private organisations across society because of the lockdown, such as (1)privacy and ethical issues in the utilisation of digital in the spaces that were previously overtly analogue in nature, (2)linked issues of digital exclusion and ensuring equity of access, and (3)how information behaviours have adapted and/or been impacted across age groups and other societal demographics. The example of the borrowing of a book brings home the issues; this universally-understood activity of visiting a library building, browsing shelves, and leaving with a physical book has been replaced with (1)visiting library website (2)downloading an app (3)logging into a third party vendor's service (4)agreeing their privacy policy, and (5)navigating their interface to download your content. This is a significant departure from the traditional experience, and raises important issues around privacy, digital equity, and information behaviour that we need to understand. By utilising FoI queries, readability and content analysis of library websites and 3rd party privacy policies, a nationwide survey of library users, and eight UK-wide focus groups, we will gain important insights into how compelled use of digital has impacted society.",2021,2022,University of Strathclyde,238376.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C09950,AH/V013483/1,Scenes of Shame and Stigma in COVID-19,"The WHO has identified social stigma and discrimination related to COVID-19 as problems that need to be urgently addressed. Evidence shows that stigma directly impacts the efficacy of health interventions, while also exacerbating health inequalities - particularly along the lines of race, ethnicity, and class. In the UK, the first months of the COVID-19 crisis have demonstrated that instances of shame, shaming, stigma and discrimination are related to, and often arise from, public health interventions. As a result, there is an urgent need to investigate, understand and address stigma and shame related to COVID-19. 'Scenes of Shame and Stigma in COVID-19' will identify various sites and circumstances of shame, shaming, stigma and discrimination during the first 12 months (January-December 2020) of COVID-19 in the UK, with a particular concern to investigate how digital technologies, neoliberal ideologies and rapid global information exchange have changed the 'scenes of shame and stigma' when compared to previous respiratory pandemics. The project will produce and communicate a body of targeted, rapid and evidence-led recommendations regarding shame, shaming, stigma and discrimination related to COVID-19 to national and global public health bodies, including Public Health England, the NHS, and the WHO. Engaging scholars in philosophy, history and cultural studies, the project will also produce scholarly work identifying and historicising the 'scenes of shame and stigma' in COVID-19, to consider (i) the affective experiences of shame/shaming and (ii) how stigma is connected to broader institutional and political structures, practices and ideologies, along with uneven distributions of social power.",2021,2022,University of Exeter,350250.81,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C09951,AH/V013297/1,COVID-19: The effectiveness of mutual-aid groups and their lessons for post-crisis community care,"Covid-19 has shown that much of the state, public sector, NGOs and elements of the private sector are slow to respond to a crisis. In many areas, mutual aid groups have mobilised quicker, responding to the needs present in their communities and/or neighbourhoods. In so doing, they highlight some of the political and procedural 'gaps' in corporate and State-led institutional emergency response programs, as well as help to identify resource allocation that hasn't been pre-planned in crisis responses (i.e. homelessness provision, national health and social care policies, food delivery etc.). However, often these locally organised groups dissipate afterwards, and their vital operational and local geographic knowledge goes under-utilised in providing more effective and appropriate community care in a post-crisis 'normal' setting. The project aims to collate, evidence and conceptually analyse 'on the ground' mutual aid groups (i.e. those working mostly off-line and in-person) that have mobilised in response to the Covid-19 crisis to care for vulnerable people in the community: e.g. people who are shielded, self-isolating, the homeless, those with long-term conditions etc. This interdisciplinary project has three distinct aims/phases. First, to comprehensively survey and thematically categorise mutual aid provision during the peak, and in the recessionary aftermath of the pandemic. Second, to undertake a deep-dive into selected case studies of categories and geographies to highlight best practice and how they related to (or substituted for) corporate/governmental responses. Third, to produce a multi-media online 'Manifesto of Mutual Aid' that explains the 'how', and crucially, the 'why' of mutual aid to effectuate better policy implementation post-crisis in conjunction with relevant governmental and non-governmental institutions.",2021,2022,Royal Holloway University of London,365369.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2020 +C09952,AH/V012789/1,"Observatory for Monitoring Data-Driven Approaches to Covid-19 (""OMDDAC"")","OMDDAC will provide a national, public space for the consolidation of knowledge and understanding around data-driven approaches to COVID-19, focused upon legal, ethical, policy and operational challenges. Data-driven responses are being developed rapidly across the public sector, academia and industry. These include combining digital health datasets within a single dashboard, use of communications data to map trends, monitoring of quarantine behaviour by drones and automated number plate recognition, and access to Bluetooth data for contact tracing. Developing technology in a 'one-dimensional' way (Nuffield Council on Bioethics 2020) without appropriate consideration of underlying values and judgements, the context and resulting interventions brings with it a high risk of errors, limited efficacy and unintended consequences for individuals. OMDACC's purpose is to provide a long-term mechanism to mitigate these risks in a way that responds to public opinion. This will be achieved by adopting an innovative mixed-methods research design, incorporating case study analysis, stakeholder interviews, representative public surveys, and the development of practitioner-focussed guidelines. By collating lessons learned throughout this period, OMDDAC will be integral to informing both policy and public thinking regarding pandemic management. It is imperative that the UK develops a framework governing the use of data-driven approaches that can be deployed during public health emergencies. Drawing on a powerful range of practical and academic expertise, and working with influential supporting partners such as the Ada Lovelace Institute, OMDDAC is designed to facilitate this process.",2021,2021,Northumbria University,455864.4,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health information systems,2020 +C09953,ES/W001225/1,#ReachIn: A rapid review of informal Social Support Interventions for victim & survivors of domestic violence & abuse,"This project aims to improve outcomes for victim-survivors of domestic violence and abuse (DVA) by advancing knowledge about informal social support interventions. The pandemic has highlighted the challenges that policing, health and frontline services face in seeking to identify and support victims-survivors of DVA. Anecdotal evidence suggests that victims have been less able and/ or willing to seek help from traditional first responders (Peterman et al., 2020) whilst more informal sources of support have faced increased demands: Refuge saw a 700% increase in the number of visits to their Helpline website during the initial lockdown (ONS, 2020). Interventions that aid informal networks (such as family, friends, neighbours and community groups) can therefore play a critical role (Sanchez et al., 2020). For those 'living with domestic abuse... the view from outside, from supportive friends, family and neighbours, is so important' (DVA Survivor, SafeLives), with the potential to improve mental and physical health outcomes for victims of DVA (Coker et al., 2004; Goodman et al., 2011). Yet, very little is known about interventions that promote, enhance, or create informal social support for adults affected by DVA. This project will review existing research to identify effective informal social support interventions and how they 'work'. A systematic rapid review will identify, describe, appraise and synthesize evidence to understand whether, and how, informal social support interventions can improve outcomes for victims and survivors of DVA. In collaboration with stakeholders, these findings will then be translated into practical, real-world guidance for friends, families and communities, as well as DVA practitioners. The collaboration between UCL and SafeLives will ensure relevance, methodological rigour, and UK-wide reach of the project and outputs. SafeLives' #ReachIn campaign will serve as a vehicle for engaging key audiences and maximising benefits now, in the recovery phase of the pandemic, and beyond.",2021,2021,University College London,116337.44,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09954,ES/W001209/1,Assessing the well-being implications of the COVID-19 restrictions on individuals affected by Parkinson's,"Individuals affected by Parkinson's have been significantly disadvantaged by the COVID-19 pandemic. In particular, the consequent social restrictions have removed many existing supports which individuals have considered vital for their well-being. While we, with Parkinson's UK, a leading UK charity, have collected some provisional data on the social effects of the pandemic on well-being, these effects are not static and neither are their impacts on well-being. Consequently this proposed project will use these data already collected as a baseline for two of the three studies within this application: one is a quantitative survey of both individuals with Parkinson's and their carers and the second is a qualitative study on the in-depth experiences of individuals with Parkinson's. For these studies further data will be collected to get a longer-term picture of the same individuals' well-being in the context of the widespread social changes. The quantitative survey data (two administrations in total) will be subject to further statistical analysis and identification of the predictors of change in well-being. The qualitative data (four administrations in total) will be analysed using interpretative phenomenological analysis. A further third study, an in-depth qualitative study, is also planned; this will focus on the experiences of carers/partners and will also be repeated and analysed longitudinally (two administrations in total). The results will be used to help inform responses from Parkinson's UK to provide appropriate support for members, to inform other third sector organisations (e.g., professional organisations) and health and social care policy-makers and to provide theoretical insights.",2021,2022,Lancaster University,259781.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09955,ES/W001195/1,The sectoral economic impacts of COVID-19 on the tourism economy: a regional analysis focussed on Scotland,"The broad patterns of changes in tourism induced by Covid-19 and the resulting containment measures - a sharp and sudden fall in international arrivals and lower international travel to the UK, plus reduced intra-UK domestic tourism flows and changed tourism behaviours - has been felt in all UK regions. Tourism is characterised by relatively low pay (its average gross wage was two-thirds of the Scottish average), high labour intensity (with its 218,000 jobs equivalent to 8% of all jobs in Scotland) and with one quarter of those jobs in rural areas. Tourism is also a key employer in many rural parts of the country, where economic resilience has tended to be more fragile than in other parts of the country. Understanding the potential economic implications of different scenarios will have important policy implications, not just on the economy but for the wider policy support landscape for different communities across Scotland. Crucially, changes in the scale and type of tourism does not impact only on tourist-facing activities, such as travel, accommodation, cultural and recreational activities, but also all those industries that are highly interconnected to tourism activities via supply chains such as such as agriculture, farming and fishing, and retail. In this project we partner with Visit Scotland to analyse the economic impact of COVID-19 on the tourism industry and aggregate Scottish economy and to provide urgently required economic analysis to the key stakeholders in the Scottish tourism industry at national and sub-national levels. There is now a pressing requirement for specialised modelling work and quantitative development of this evidence base, to inform decision-making for Scotland's crucial tourism industry in the process of recovering from the COVID-19 pandemic. There are two parts to the work which will occur through the project's duration. Firstly, it will bring together researchers and stakeholders from the tourism industry in the development of quantitative scenarios - building on already-developed qualitative scenarios by the Scottish Tourism Economic Recovery Group (STERG). These will set out agreed projections for the path of tourism under alternative scenarios, including policies. Secondly, the work will take these projections as inputs to an economic modelling framework for Scotland which will set out impacts of these scenarios. The results will capture impacts on the economy as a whole as well as on individual industries, including those directly exposed to tourism spending and the knock-on effects on linked industries across the whole economy and sub-regions of Scotland. This project will help STERG and policy makers at national and sub-national level in Scotland to fully understand the implications and magnitude of the various scenarios for Scottish tourism, in particular a worst-case 'three winters scenario'. This will ensure the current quantitative knowledge gap is filled and appropriate policy responses are effective in supporting economic recovery.",2021,2022,University of Strathclyde,237688.61,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C09956,ES/W001187/1,Understanding the social impacts of coronavirus under different health restrictions: Longitudinal analysis using the ONS OPN Covid-19 survey,"Data from the 'Coronavirus and the Social Impacts on Great Britain' survey are used to assess social impacts as the COVID-19 crisis deepens. This project reports on the social impacts of the coronavirus pandemic on people's health and subjective wellbeing (SWB) in Great Britain; reports on the public understanding of information about the coronavirus, along with people's behavioural responses and actions to prevent disease spread; reports on how individuals, families and communities are coping and managing risks, considering behavioural impacts and lifestyle changes and how people are building resilience during the pandemic and the social impacts under different conditions and governmental restrictions. The study adopts a longitudinal approach to social impacts by merging survey data covering the period March 2020 to September 2021. This provides a combined sample size of c.70,000 respondents, with sufficient statistical power to support a detailed subnational level analysis. This policy-orientated research is made possible thanks to the new Coronavirus and social impacts survey that has been in continual operation since March 2020. The data from this survey is made available to accredited researchers by the UK Office for National Statistics.",2021,2022,University of Strathclyde,209659.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09957,ES/W001152/1,Student to Degree Mismatch: The Role of Schools and the Impact Of Disruption From Covid-19,"A level grades are crucial in determining how students match with university courses. Previous research by the team (Campbell et al, 2020) finds lower SES students are more likely to 'undermatch' - attending less selective courses than expected given their A level grades - and less likely to overmatch (the reverse). This matters for social mobility since attending a higher-tariff course leads to higher future earnings (Belfield et al, 2018). In 2020, A levels were cancelled due to COVID-19, and most students received Centre Assessed Grades (CAGs), predicted by teachers. Research (Murphy and Wyness, 2020; Anders et al., 2020), shows that high SES and private school students receive more generous predictions. They also have better information, advice and guidance, a key driver of attending higher-tariff courses. Meanwhile, universities were expanding places over fears of fewer overseas students attending, numbers caps were abandoned, and they were legally obliged to accept students they made offers to. This perfect storm could advantage high SES students, impacting the extent of mismatch, and the SES gap. In this project we will: 1) examine the impact of exam cancellations on student to course mismatch, 2) examine the characteristics of mismatched students (by school type and SES) in 2020 versus 2019, 3) provide new evidence on the consequences of mismatch for degree outcomes, describing the potential impact on equity and mobility. Led by Dr Gill Wyness, with Professor Lindsey Macmillan and Dr Jo Blanden, the team combines world leading expertise in education, social mobility, and the study of mismatch.",2021,2022,University College London,248334.62,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09958,BB/V01997X/1,"High-resolution structure, function, and anti-viral inhibition of the SARS-CoV2 E protein ion channel","The Covid19-causing SARS-coronavirus-2 (SARS-CoV2) contains a small number of proteins, three of which reside in its membrane. They include the spike protein (S), responsible for attachment to the host, the membrane protein (M), and a cation-channel (membrane pore) formed by the envelope protein (E), CoV2E. Cation flow through the E-protein of SARS-coronaviruses (SARS-CoV) plays a role in virus replication in host cells. Inhibitors of the E-protein channel have been shown to substantially diminish virulence of SARS-CoV, the coronavirus responsible for the SARS outbreak in 2003. Inhibitors of CoV2E cation flux are expected to attenuate SARS-CoV2 pathogenicity and their discovery is the goal of this application. Repurposing drugs originally developed for other diseases offer a fast-track to new treatments. These will be included in the current study to expedite delivery of effective drugs. Structure-based drug design is another means to accelerate the discovery of drugs by enabling focused, rational approaches to design and repurposing. However, the structure of CoV2E is only partially known. We thus propose to (i) solve high-resolution crystal-structures of CoV2E, (ii) apply computational electrophysiology and in silico screens including cheminformatics/machine learning approaches to identify CoV2E inhibitors from libraries of commercially available and repurposing drugs, and (iii) perform lead validation and further development of inhibitors by electrophysiology and crystallography.",2021,2022,University of Dundee,699363.21,Viruses,Not applicable,Not Applicable,,Not applicable,Not applicable,,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C09959,BB/V019929/1,SARS-CoV-2 infections in cats: assessing their zoonotic potential and role in sustaining the COVID-19 pandemic,"SARS-CoV-2 is a new coronavirus of animal origin that recently emerged in humans and has spread rapidly across the world. It is likely that SARS-CoV-2 will establish as an endemic virus of humans, which has the potential to lead to infections in animals that live in close proximity to humans. There have been sporadic reports of infections in pet cats in households with COVID-19 patients, which demonstrates that cats are susceptible to SARS-CoV-2 infection. This means that cats could potentially act as virus reservoirs, or sources of infection for other species. Experimental infections have demonstrated that cats are susceptible to SARS-CoV-2 infection and infected cats are capable of transmitting SARS-CoV-2 to other cats. The virus replicates in the respiratory tract and infectious virus can be detected in nasal washes, oropharyngeal and rectal swabs. In addition, traces of the virus have been detected in faeces and occasionally urine. The risk of human-to-cat infection and the potential for the establishment of cats as a reservoir for SARS-CoV-2 is unknown. In light of recent reports in The Netherlands and Denmark of SARS-CoV-2 jumping from humans into mink, transmitting between mink and then jumping back into humans, further research is warranted to investigate animals that are susceptible to COVID-19, including domestic pets. In this project we will investigate the susceptibility of domestic cats to SARS-CoV-2 infection and their capacity to transmit the virus to cats and other species as the pandemic progresses. A successful cross-species jump of SARS-CoV-2 from humans into cats not only expands the host range of the virus but might also generate an additional source of infections for humans and other species, which would make the elimination of SARS-CoV-2 more complex. Only by assessing the potential of SARS-CoV-2 viruses isolated from cats to infect other species, including humans, will it be possible to effectively gauge and control virus transmission to all potentially susceptible species.",2021,2022,University of Glasgow,468259.03,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +C09960,MC_PC_20053,MRC Pandemic Preparedness Funding - The Francis Crick Institute,"This funding will enable the Institute to address two major aims: i)             understanding the coronavirus pathogen, including viral assembly, host factors and exploitation of structural components for the development of therapeutic targets; ii)            understanding the features of host response to infection that shape protective or pathological responses and defining correlates of immunity and immune pathology.",2021,2021,The Francis Crick Institute,1688850,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +C09961,MC_PC_20052,Non-hospitalised Children & young people (CYP) with Long Covid (The CLoCk Study),"Uncertainties relate to diagnosis, prevalence, duration and treatment of post-COVID syndrome ('long COVID') in children and young people (CYP). There is no diagnostic test nor definition for long COVID. We do not know the physical, psychological andsocial consequences of long COVID and we need to define the clinical phenotype and longer-term physical/physiological/psychological changes to target therapeutic interventions. Risk factors for acute COVID include: obesity, pre-existing co-morbidities, learning and neurological disabilities, mental health(MH) problems, BAME status. The CYP likely to be most at risk of long COVID are teenagers as they represent the majority of CYP pre-COVID with persistent physical and MH symptoms post-viral infection. Ludwigsson (2020) reported five COVID positive CYP with median age 12 yrs with symptoms longer than 6 months.The research questions: 1. To describe the clinical phenotype of post-COVID symptomatology in test-positive CYP, using test-negativecomparators 2. Use these data to produce an operational definition of long COVID, necessary for any future epidemiological orinterventional study 3. Use this definition to establish the prevalence and natural course of long COVID in CYP to inform NHS services and health policy HYPOTHESIS: the type, prevalence and trajectory of symptoms in COVID positive CYP will differ significantly from thecomparator group, allowing us to construct an operational definition of long COVID. We plan a longitudinal cohort study of non-hospitalised CYP aged 11-17 yrs. We will approach 30,000 CYP, half of whom with proven COVID. We expect 6,000 to consent to help us. We will ask them whether they still have physical or mental health problems at 3, 6,12 and 24 months afterwards. The 3,000 CYP with a positive SARS-CoV-2 tests will be compared with 3,000 test-negative controls. DELIVERABLES: we will access large numbers with proven COVID quickly to generate early outputs to inform future intervention studies and health policy.",2021,2024,"University College London, Great Ormond Street Hospital",1299613.86,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Epidemiological studies,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences | Disease surveillance & mapping,2021 +C09962,MC_PC_20050,"Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)","Background Approximately 1 in 20 individuals with COVID-19 experience symptoms and impaired quality of life beyond 12 weeks ('Long COVID'). Long COVID may comprise several distinct syndromes yet to be fully characterised. Aim: To evaluate symptoms and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals, to coproduce a remotely-delivered intervention, and to establish a virtual trial platform. Objectives and Methods WP1 Establish a representative population-based cohort of individuals with Long COVID. A representative population-based cohort of non-hospitalised individuals with Long COVID will be established using Clinical Practice Research Datalink (CPRD) primary care records. Individuals with a diagnosis of COVID-19 at least 12 weeks prior and matched controls will be identified. We will invite them to report symptoms/quality of life through the Aparito Atom5™ digitalplatform. WP2 Characterise and immunologically phenotype Long COVID syndromes. Machine learning clustering techniques will be used to identify distinct Long COVID syndromes. Individuals from each cluster(n=50) and controls will be invited to undertake biosampling to measure inflammatory markers, autoantibodies, and T cellfunction, and wearable devices to provide data on heart rate, oxygen saturation, physical activity and sleep quality to identify potential pharmacological and supportive therapies. WP3 Provide evidence-based recommendations on targeted pharmacological and supportive therapies for Long COVID syndromes.We will review existing evidence on post-viral inflammatory syndromes and existing evidence on Long COVID to prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers.WP4 Co-produce and evaluate a virtual targeted supportive intervention for Long COVID. A digital trial platform will be established to evaluate the effectiveness, cost-effectiveness, and acceptability of the coproduced virtual supportive intervention in a randomised clinical trial, and for future research.",2021,2023,University of Birmingham,1568724.81,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C09963,EP/V034529/1,"Improving emotional, economic and behavioural resilience to COVID-19 in African University students","The Covid-19 pandemic has had significant adverse effects on university students, whose education and training has been severely disrupted and their social contacts and job prospects lost. Even before the pandemic around of a third of students would had had symptoms of depression, with students who are economically disadvantaged at greatest risk. Depressed students do less well academically which has negative impacts on their employment prospects and they are also less likely to follow health advice. Thus depressed students are particularly vulnerable to the health and economic impacts of the COVID-19 pandemic. This is a particular concern for students in less developed countries such as Zambia where access to mental health services is limited by the lack of resources and by the stigma associated with psychiatric illness. This study aims to address this cycle of disadvantage by providing targeted access to an effective, online treatment programme for depression (moodgym) to a 1000 students who identify themselves as having symptoms of depression. These students will be recruited from universities in Zambia, Malawi and Botswana: all countries identified as eligible for overseas development assistance. Moodgym is based on principles of cognitive behavioural therapy and aims to reduce the risk of depression by helping users to recognize and change those negative thoughts and behaviour patterns which can drive and sustain low mood. The 5 modules are particularly aimed at young people aged 15 to 25 and include exercises, practical assignments and quizzes. This study will investigate whether combining moodgym with a university-wide online COVID-19 prevention programme will improve students' mental health and enhance their ability to withstand the health and economic challenges of COVID-19. The online COVID-19 prevention program, adapted for each local context, will portray health-promotion behaviours such as social distancing and face coverings as a normal part of student life. We will collect feedback data from the prevention programme and survey data before and after the moodgym/ COVID-19 prevention programme intervention to look for improvements in depression, academic performance and COVID prevention behaviours and to check whether benefits are felt equally by men and women. We will also interview participants to try to understand how moodgyam helped them and to explore their feelings about the impact of COVID-19 on their mood and their studies. We also want to find out which factors are associated with improved mental health and academic outcomes so that we can ensure the intervention's sustainability and successful implementation in other less developed countries.",2021,2022,University of Nottingham,148884.29,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Zambia | Malawi | Botswana,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C09964,EP/W002779/1,Airborne Infection Reduction through Building Operation and Design for SARS-CoV-2 (AIRBODS),"This research will deliver robust guidance on ventilation operation and future building design to reduce SARS-CoV-2 transmission in buildings - such as primary healthcare settings, theatres, open plan offices and retail spaces - in response to increasing evidence of aerosol transmission. This work brings together leading UK scientists and engineers to address this using experimental methods, mathematical modelling and field work. By undertaking small-scale experiments and field tests to investigate the transport of aerosols carrying virus particles under various scenarios, the team will develop guidance on how to design and operate buildings to minimise the risk of airborne transmission, and develop a range of modelling techniques and simulation tools for others to use to enable immediate deployment of knowledge. With CIBSE as a project partner, and a work package dedicated to dissemination, we will operate a very transparent channel of regular communication with stakeholders. Through this channel the team will provide advice and guidance, as it becomes available, on mitigating airborne transmission. However, the longitudinal nature of the research means we will refine our models using feedback from field studies and be in a position to respond to the changing demands for information and advice to help society ""reopen for business"". Our approach to the research will mean the knowledge and tools we generate will be relevant for mitigation of a wide range of airborne hazards across the spectrum of indoor environments for many years to come.",2021,2022,Loughborough University,1746234.76,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2021 +C09965,EP/V034057/1,STAMINA: Strategies to Mitigate Nutritional Risks among mothers and infants under 2 years in low income urban households in Peru during COVID-19,"Peru's progress in combatting malnutrition may be reversed with the current COVID-19 pandemic which has caused disruption of maternal and infant nutrition services, closure of health centres and rising unemployment. Peru has experienced one of the highest mortality rates from COVID-19 in South America. Deteriorations in infant nutrition will lead to poorer health outcomes for the next generation. Government and community stakeholders in Peru have highlighted the unknown impacts of the pandemic on the nutrition of mothers and their infants and young children. This study will examine how the COVID-19 response is impacting on the nutritional risks of mothers and infants (aged 0-23 months) within the household setting in low-income areas of two cities, Huánuco and Lima. This information will be compared with detailed nutritional assessments conducted in the same communities immediately before the national State of Emergency due to COVID-19. To address the emerging nutritional risks, we will work with stakeholders to co-create adapted methods for the delivery of nutritional services including iron supplementation and support for exclusive and continued breastfeeding. We will identify the nutritional risks resulting from the COVID-19 pandemic by examining short, medium and longer term changes in: - exclusive breastfeeding rates for infants aged 0-6 months; continued breastfeeding for infants aged 6-23 months, and the extent to which WHO recommended complementary feeding practices are being met. - the uptake of iron supplementation in infants and young children - a national priority to combat anaemia - in the context of the disrupted health services and new delivery strategies implemented since the pandemic. - household food security, maternal psychological wellbeing, and changing quality of diet in relation to nutritional risks of undernutrition as well as overweight and obesity at the household level. - how household dietary practices adapt and respond to the ongoing pandemic. With these insights, we will co-create support systems for the design or adapted delivery of nutritional counselling, growth monitoring and iron supplementation for infants and young children using information and communication technologies or socially-distanced health services. We will work with UNICEF Peru as a project partner in order to ensure that efforts to address malnutrition target the most vulnerable groups and are tailored to the challenges experienced by urban communities which make up the majority population of Peru.",2021,2022,Loughborough University,217611.45,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Urban Population/Setting,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Peru,Peru,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C09966,964728,JIU-JITSU WITH MISINFORMATION IN THE AGE OF COVID: USING REFUTATION-BASED LEARNING TO ENHANCE VACCINE UPTAKE AND KNOWLEDGE AMONG HEALTHCARE PROFESSIONALS AND THE PUBLIC,"Vaccine hesitancy-the delay or refusal of vaccination without medical indication-has been cited as a serious threat to global health by the World Health Organization (WHO), attributing it to misinformation on the internet. The WHO has also identified Health Care Professionals (HCPs) as the most trusted influencers of vaccination decisions. JITSUVAX leverages those insights to turn toxic misinformation into a potential asset based on two premises: 1. The best way to acquire knowledge and to combat misperceptions is by employing misinformation itself, either in weakened doses as a cognitive ""vaccine"", or through thorough analysis of misinformation during ""refutational learning"". 2. HCPs form the critical link between vaccination policies and vaccine uptake. The principal objective of JITSUVAX is to leverage misinformation about vaccinations into an opportunity by training HCPs through inoculation and refutational learning, thereby neutralizing misinformation among HCPs and enabling them to communicate more effectively with patients. JITSUVAX comprises 4 scientific work packages (WPs 1-4), plus one Management WP (WP0). WP1 will systematically measure HCP attitudes towards vaccinations across participating countries. WP2 will analyse argumentation by anti-vaccination activists to provide material for inoculation and refutational learning. WP2 will also develop novel tools that improve public resilience to misinformation and HCP's knowledge and attitudes concerning vaccinations. WP3 will translate the findings from WP1 and WP2 into practice, by exploring several new tools, ranging from a new ""empathic refutational interview"" to interventions in the training of HCPs. WP4 focuses on impact and dissemination. WP4 will design and develop a guidance document for HCPs and public health bodies. Through the team's contacts and previous collaborations with WHO and UNICEF, we will disseminate and leverage our new knowledge for global impact.",2021,2025,UNIVERSITY OF BRISTOL,3800892.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Health Systems Research",Communication | Vaccine/Therapeutic/ treatment hesitancy | Health workforce,2021 +C09970,AH/V015842/1,Grading Gowns: Redesigning One-size PPE To Fit And Protect Female Health Workers More Effectively,"Since the outbreak of COVID-19, a shortage of suitable PPE has resulted in healthcare workers(HCWs) wearing one-size, disposable isolation gowns, compromising comfort and safety. Oversized, ill-fitting gowns impede movement and increase body temperature and risk of viral transmission. Clinical procurement and acute care leads have expressed the need for more sustainable, reusable, individually sized PPE gowns fabricated from washable textiles to enhance the HCWs experiences, while mitigating infection risk and reducing clinical waste. The project will deliver a 'reusable PPE isolation gown system' including a doffing accessory to safely remove contaminated gowns. The healthcare sector ready set of gowns will be designed and produced in EN-certificated textiles and manufacturing conditions in multiple sizes (XS-XXXL) informed by: a systematic review of current PPE design, provision and use; qualitative data from interviews, questionnaires and wearer trials. The PPE outcomes will be disseminated via UK NHS trusts, health authorities, service conferences and publications. The investigators have industry/ research expertise in user-centred fashion and workwear design. Alexandra, is an industry leader in the production and supply of PPE gowns to UK health authorities and links with the Chelsea and Westminster NHS Foundation Trust. Other NHS partners include clinical procurement and acute care team leaders who have in-depth knowledge of the acquisition, distribution, use and affect of disposable PPE. The applicants' universities encompass the product design labs and resources required for fashion/ accessory development and prototyping. Alexandra will provide access to advanced clinical textiles, gown production and testing facilities. Interviews, questionnaires and wearer trials will facilitated via London, Northampton and Nottingham hospitals.",2021,2022,Nottingham Trent University,253410.9,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C09971,AH/V015214/1,The Role of Good Governance and the Rule of Law in Building Public Trust in Data-Driven Responses to Public Health Emergencies,"This research, at the intersection of law, ethics, citizen deliberation, public health and data science, aims to develop a distinct arts and humanities, values-based framework to help understand and address the challenges posed by data-driven responses to public health emergencies and the need to build public trust. In their COVID-19 responses, states have relied on data-driven approaches to justify far-reaching measures including closing entire business sectors and categories of travel, curtailing personal liberties and requiring compliance with new technologies for contact tracing and social distancing. To be effective, such measures must be internationally co-ordinated, nationally adopted and adhered to by a high proportion of the public. Trust underpins both national adoption and public adherence: trust in international institutions, in the measures, and their scientific foundations. This project will examine two critical enablers of that trust: good governance and the rule of law. It aims to provide practical guidance on how international and national institutions can build public trust in the processes by which they design and implement data-driven responses to public health emergencies. The research consists of four interconnected work packages which examine (1) International governance frameworks for public health emergencies (2) Values-based principles to guide data-driven responses by national institutions including governments, parliaments, courts and police (3) Reforms that may be needed to data governance (national and international) given the scale of personal data sharing that is required (4) A citizen jury deliberation on the trustworthiness of data-driven measures and what additional safeguards may be needed.",2021,2021,British Institute of International and Comparative Law,568571.16,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C09972,AH/V015133/1,Public Health Messaging during the COVID Pandemic: Dating App Usage and Sexual Wellbeing among Men Who have Sex with Men,"Public health measures to mitigate the spread of coronavirus are translated into media messaging by organisations that target the health of different groups. Engaging experiences of the minority group of men who have sex with men (MSM), we will provide rapid evidence on the approaches and responses to these messages in relation to using digital platforms to connect for sexual purposes. Organisations have variously advised MSM to practice sexual abstinence, engage in digitally mediated sexual encounters or wear masks and avoiding the exchange of saliva during sex. Campaigns are running which present the situation as a route to ending HIV. Yet, 8/7/2020 the government cut £5M from the pre-exposure prophylaxis budget - an effective of reducing HIV transmission. We must understand MSM's reception of these messages to impact upon policy and practice for this group, shed light on what to look for where minorities are concerned, and provide learning about COVID public health messaging that will benefit the general population. To do this, we will: > Run three online surveys to generate data about public sexual health messaging reception, and dating/hooking up practices (WP1); > Undertake a discourse analysis of the web page resources created by organisations who support the health and wellbeing of MSM, and of the messaging provided by online dating and hook up apps (WP2); > Collect historical and ongoing conversational data from selected social and digital media frequented by MSM. This data will be contextualised by analysing the media they are generated with using the walkthrough method (WP3).",2021,2022,University of Salford,298296.78,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2021 +C09973,AH/V015028/1,"UK Museums during the COVID-19 crisis: Assessing risk, closure, and resilience","Museums are a vital part of the UK's cultural and economic landscape. In England alone, they attract 100 million annual visits and have a turnover of £2.64 billion per annum. Senior staff in governmental and non-governmental museum agencies are deeply concerned that many museums will not survive the impact of COVID-19 with a correlative loss to the cultural and economic landscape. Although museum agencies are urgently seeking funding and developing policy to manage the impact of COVID-19, they do not have established mechanisms for gathering comprehensive data on the UK museum sector, for tracking which museums are at risk of closure, and which actually close. Thus, they proceed with inadequate information. This project will provide museum agencies with rigorous, timely data on which museums are at risk of closure, which museums close, which remain resilient, and how the profile of the UK museum sector changes as a result of COVID-19. We will develop indicators for risk and resilience that are applicable within the current crisis and assess whether the closures that occur have a disproportionate impact on particular audiences and localities. The research draws on the expertise of an existing research team and combines quantitative and qualitative techniques including web-scraping, natural language processing, interview-based research, and primary data collection.",2021,2022,"Birkbeck, University of London",211435.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +C09974,ES/W001039/1,COVID BAME Highlight: Religious community organisations' interventions around the impact of Coronavirus on Muslims in Birmingham in post-Covid Britain,"The research will focus on Muslim communities living in Washwood Heath, Bordesly Green, Sparkbrook and Handsworth, Birmingham, UK, and the responses to the COVID pandemic by religious community leaders, community organisations and Mosques within these communities. The UCL Institute of Health Informatics has shown that BAME individuals are two-three times more likely to die from Covid-19 than the white population (UCL 2020). Specifically, the risk of death from Covid-19 is: 3.29 times higher for Pakistanis than the general population; 3.24 times higher for Black Africans; 2.41 times higher for Bangladeshis; 2.21 times higher for Black Caribbean and 1.7 times higher for British Indians (UCL 2020). The above data clearly indicates that Muslims from BAME backgrounds are at significantly elevated risk. Furthermore, 73.7% Of Muslims in the UK are from South Asian groups and 88.5% are from BAME backgrounds (MCB 2015), with the Annual Population Survey documenting 301,000 Muslims living in Birmingham (ONS 2018). The research will focus on impacts on Muslims living in the wards identified around perceptions of vulnerability post-lockdown; state responses including the policing of social distancing measures and NHS responses to COVID-19; and responses by local Mosques to facilitate collective worship, rituals around burial and community connectedness. Data will be collected through online surveys with Mosques and semi-structured interviews and focus groups with community members and religious leaders. The research will develop applicable interventions based on responses by Mosques and other Muslim community organisations, deliverable in partnership with local government agencies in Birmingham and in the UK more widely. Muslim communities in Birmingham have been among the most affected black and minority ethnic groups to be impacted by COVID-19. The proposed research covers a range of bases which will be integral to identifying areas of need and more pertinently, areas of limitation in local government responses and the ways in which these have been partially filled by community-led initiatives. Through documenting these areas of need and identifying desired and appropriate responses, the insights from the research will allow for effective strategies to be developed specifically to the needs of British Muslims as a particularly vulnerable group within the context of the pandemic. These strategies will be documented in practical terms through toolkits, a written report, and two proposed conferences (both to be delivered in person and live streamed) to facilitate access for Muslim communities, and black and minority ethnic communities across the country more generally. Impact will be focused on alleviating vulnerability within Muslim communities in Birmingham initially, and on the national level later on. The research is significant not least because we will gain an insight into the experiences of Muslims as one of the most vulnerable communities to include black and minority ethnic groups. But we will also gather insights into the implications of the pandemic for religious observance, collective worship obligatory rituals around burial, and the role of Mosques for the community in times of extreme need. We will also look at perceptions of state responses held within Muslim communities in Birmingham, including concerns around the rollout of vaccines. Understanding the complexities of how these factors are related is necessary in order to fully understand areas of need for Muslim communities within the context of COVID-19 Britain.",2021,2022,Birmingham City University,180256.59,Human Populations,Black | Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09975,ES/W000881/1,Co-POWeR - Consortium on Practices of Wellbeing and Resilience in BAME Families and Communities,"Two viruses - COVID-19 and discrimination - are currently killing in the UK (Solanke 2020), especially within BAMEFC who are hardest hit. Survivors face ongoing damage to wellbeing and resilience, in terms of physical and mental health as well as social, cultural and economic (non-medical) consequences. Psychosocial (ADCS 2020; The Children's Society 2020)/ physical trauma of those diseased and deceased, disproportionate job-loss (Hu 2020) multigenerational housing, disrupted care chains (Rai 2016) lack of access to culture, education and exercise, poor nutrition, 'over-policing' (BigBrotherWatch 2020) hit BAMEFC severely. Local 'lockdowns' illustrate how easily BAMEFC become subject to stigmatization and discrimination through 'mis-infodemics' (IOM 2020). The impact of these viruses cause long-term poor outcomes. While systemic deficiencies have stimulated BAMEFC agency, producing solidarity under emergency, BAMEFC vulnerability remains, requiring official support. The issues are complex thus we focus on the interlinked and 'intersectional nature of forms of exclusion and disadvantage', operationalised through the idea of a 'cycle of wellbeing and resilience' (CWAR) which recognises how COVID-19 places significant stress upon BAMEFC structures and the impact of COVID-19 and discrimination on different BAMEFC cohorts across the UK, in whose lives existing health inequalities are compounded by a myriad of structural inequalities. Given the prevalence of multi-generational households, BAMEFC are likely to experience these as a complex of jostling over-lapping stressors: over-policed unemployed young adults are more likely to live with keyworkers using public transport to attend jobs in the front line, serving elders as formal/informal carers, neglecting their health thus exacerbating co-morbidities and struggling to feed children who are unable to attend school, resulting in nutritional and digital deprivation. Historical research shows race/class dimensions to national emergencies (e.g. Hurricane Katrina) but most research focuses on the COVID-19 experience of white families/communities. Co-POWeR recommendations will emerge from culturally and racially sensitive social science research on wellbeing and resilience providing context as an essential strand for the success of biomedical and policy interventions (e.g. vaccines, mass testing). We will enhance official decision-making through strengthening cultural competence in ongoing responses to COVID-19 thereby maximizing success of national strategy. Evidenced recommendations will enable official mitigation of disproportionate damage to wellbeing and resilience in BAMEFC. Empowerment is a core consortium value. Supporting UKRI goals for an inclusive research culture, we promote co-design and co-production to create a multi-disciplinary BAME research community spanning multi-cultural UK to inform policy. CO-POWeR investigates the synergistic effect on different age groups of challenges including policing, child welfare, caring and physical activity and nutrition. WP1 Emergency Powers investigates these vague powers to understand their impact on practices of wellbeing and resilience across BAMEFC. WP2 Children, Young People and their Families investigates implications for children/young people in BAMEFC who experience COVID-19 negatively due to disproportionate socio-economic and psychosocial impacts on their families and communities. WP3 Care, Caring and Carers investigates the interaction of care, caring and carers within BAMEFC to identify how to increase the wellbeing and resilience of older people, and paid and unpaid carers. WP4 Physical Activity and Nutrition investigates improving resilience and wellbeing by tackling vulnerability to underlying health conditions in BAMEFC. WP5 Empowering BAMEFC through Positive Narratives channels research from WP1-4 to coproduce fiction",2021,2022,University of Leeds,2843976.14,Human Populations,Asian | Black | Other | Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Minority communities unspecified | Other,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Indirect health impacts | Economic impacts,2021 +C09976,ES/W000849/1,"The social, cultural and economic impacts of the pandemic on ethnic and racialised groups in the UK","The Covid-19 pandemic has thrown existing patterns of ethnic inequality in Britain into sharp relief, highlighting the vulnerability of ethnic and racialized communities not only in terms of poor health, but across a range of social and economic arenas. The Centre on the Dynamics of Ethnicity (CoDE) has pioneered innovative, policy relevant and impactful multi-disciplinary and mixed-methods social research on ethnic inequality since 2012. Building on this track record, and on new research on the pandemic, the programme will examine the impact of the crisis on ethnic and racialized people and communities, in the context of Brexit, an economic downturn and the increased awareness of racial inequality in the wake of the Black Lives Matters protests, and the rise of racist and anti-racist activism. The programme offers new insights into key policy areas highlighted as concerns as the pandemic has progressed: health inequalities and ageing populations; housing and welfare; education, employment and policing; cultural politics, activism and resilience. The projects employ innovative quantitative and qualitative methods to examine emergent forms of ethnic inequality at multiple scales, from the household and community (micro), institutional (meso), to economic and demographic change (macro). The programme includes work packages which use a survey and the new 2021 census data to explore emerging patterns of racial and ethnic disadvantage related to the pandemic. It will also track the impact of Covid-19 on both physical and mental health of racialized groups, with a focus on older and vulnerable migrant communities. This work will identify gaps in our understanding of the vulnerability of racialized groups and ethnic minorities to Covid-19 and identify routes to filling these gaps, including linking data and the need for the collection of new data. Work packages will explore the impact of austerity and Covid-19 on housing inequalities in specific places as well as tracing the impact on labour market inequalities and their routes in education. The use of algorithms in education and policing will be explored. There will also be examination of the nature of memorialising and mourning in the wake of the pandemic in the context of new forms of community and political activism. The projects foreground the intersection of ethnicity with divisions around migration and citizenship status; the role of gender, religion and age; local/community, regional, sub-national and national level differences; the engagement of ethnic minorities with key institutions and trust in these institutions. The programme will work in partnership with key public and private sector, government and NGO organisations to maximise the reach and impact of its work. This will include a programme of events highlighting the research, continuation of the CoDE covid briefings series and communication on social media, through mainstream media, and in blogs and the website.",2021,2022,The University of Manchester,3109414.71,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09977,ES/V006436/1,Mapping spatial practices and social distancing in smart schools: sensory and digital ethnographic methods,"This 18 month interdisciplinary project collaborates across the fields of Education, Architecture, and Design to improve our understanding of the lived experience of school buildings. This project combines sensory ethnographic methods with social mapping methods, to trace complex networks of relationality and spatial practices in buildings. Our aim is to generate new mapping methods that better document the sensory-affective dimensions of school environments. These dynamic maps will offer time-lapse representations of how staff and students experience the school buildings, shedding light on problematic spaces in the built environment. This constitutes a cutting-edge methodological approach that assembles participatory methods of design-based research with sensory ethnographic mapping. This hybrid ethnographic method involves following the key actors involved (staff, students, visitors, stakeholders), while also attending to the sensory force and impact of the built environment itself. The research team will collect sensory ethnographic data, codify and correlate with voiced/texted concerns regarding building use, assemble the data using mapping software, and create dynamic visualizations of the spatial practices and sensory environment, as it mutates over a 9 month period of time. Working with three secondary schools in Liverpool, our iterative research design involves alternating between 3-month cycles of ethnographic study and 3-month cycles of data processing and map making, for a total of 9 months in the schools. Our methods directly involve school communities in collaborative processes of collectively mapping the complex sensory-affective spatial practices within their buildings. Young people at the schools will increase their understanding of smart architecture and passive sensor technology through their participation in the project. Workshops with students and staff will commence in the first 2 months, exploring participatory methods for sensory ethnography in smart schools. The cycles of ethnography and mapping will follow. Co-designed interventions in schools aim to address problematic spaces during mapping phases. The research team will meet with an advisory group 5 times over the 18 months, which includes experts in UK school architecture, learning environments, and digital design, as well as representatives from the schools. We are partnering with an architecture firm esteemed for their school architecture, and their national and international contributions, over the last two decades, to education learning environment policy. The participating schools were built by the architecture firm, which is contributing person-hours throughout the project, as well as school architectural plans and blueprints, and other planning documents used to visualize the occupant experience. We are also working with a design company that focuses on innovative wearable sensor technologies and citizen science, with experience in school building interventions. The project is situated in our Manifold Laboratory for Biosocial, Eco-sensory, and Digital Studies of Learning and Behaviour, where we have access to equipment and research infrastructure (www.biosocialresearchlab.com). Academic and creative outputs will include (a) a project website, documenting both research process and findings, with a secure blog for posting news and progress, (b) project exhibitions and events in Liverpool public-access sites, such as The Baltic Triangle PLACED digital academy, and Make Liverpool North Docks Warehouse, and the Manchester Whitworth Young Contemporaries space, and Manchester School of Architecture, (c) academic publications (3), conference papers (3), and a report to local education agencies. Findings will also be shared with the Association for Learning Environments (ALE-UK), the UK National Data Archive, and the learning environment group at the OECD.",2021,-99,Manchester Metropolitan University,223737.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C09978,ES/T000066/1,Changing research practice: undertaking social science research in the context of COVID-19,"This new and urgent project from NCRM and funded by the ESRC is looking at how Covid-19 is disrupting our research practice by challenging researchers who are conducting social research to re-consider their designs, re-think their ethics, broker different kinds of access, and adapt their research methods. Responding to the public health mandates, limitations on contact and access, and disruption to people's lives researchers are moving swiftly and sharing accounts, advice and resources on social media and in research papers. Via this project NCRM researchers are playing a key role by engaging with and facilitating timely debates, synthesising useful evidence, and sharing solutions to the challenges. The NCRM portal will offer a response hub to support researchers developing and adapting methods in this challenging period with a view to lasting impact for research communities.",2021,-99,National Centre for Research Methods,30896.92,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C09979,ES/W002507/1,COHERE phase 2: Living systematic reviews and evidence and gap map on determinants of COVID-19 Health Related Behaviour,"1,2] synthesise evidence on the factors that influence uptake and adherence to protective behaviours to inform the development of public health interventions. Rapid reviews, or restricted reviews, necessarily fall short of the full rigour of a traditional systematic review to deliver answers faster but with greater uncertainty",2021,2022,Queen's University Belfast,432925.23,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2021 +C09980,ES/W001721/1,Exploring the psychological drivers and impact of public health communications on vaccination beliefs of minority ethnic groups,"Psychological drivers of behaviour can help explain why individuals engage in protective and risky health behaviours. Understanding behavioural determinants can inform strategies to promote behaviour change and using a theory-driven approach underpinned by behavioural science, facilitates a more detailed understanding of mechanisms of change. Evidence indicates some minority ethnic groups have lower intentions to receive a COVID-19 vaccine. This is of considerable concern given higher COVID-19 incidence, morbidity, and mortality among minority ethnic groups. There is limited evidence of the reasons underpinning COVID-19 vaccine hesitancy in minority ethnic groups in the UK, but emerging evidence indicates it is related to beliefs about vaccine safety/efficacy and issues of mistrust towards formal services, as well as practical barriers such as access. This study will involve three waves of in-depth interviews and focus groups with minority ethnic community members and organisations in London and Birmingham to understand (i) specific barriers and facilitators of vaccine uptake, (ii) changes in COVID-19 vaccination risk perceptions over time, (iii) challenges and strategies for building and sustaining community support for vaccination programmes, and (iv) the impact of public health campaigns on vaccination intention. We will also evaluate national and local campaigns across the UK to identify mechanisms of action of health messages using a behavioural science framework. This will facilitate the rapid development of evidence-based, theoretically informed, tailored health messages that are critical for the ongoing success of the UK mass vaccination programme. It will also support the sustained community engagement that is crucial for optimising public health outcomes.",2021,-99,King's College London,363421.06,Human Populations,Other,Unspecified,Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy, +C09981,ES/W001837/1,"The impact and implications of Covid-19 on the relational, social, and healthcare experiences of hospice care in the West Midlands","People with life limiting conditions are some of the most vulnerable to Covid-19. Until recently, hospice care has largely been associated with in-person, specialist, and buildingcentric support. Covid-19 has been a catalyst to its redesign, bringing rapid and on-going changes that are affecting every aspect of hospice care and support for the dying. However, we do not know how effective these changes to hospice services have been, how they have affected experiences of providing or receiving hospice care and support, and if these changes may have been experienced unevenly. The study's aim is to identify nationally relevant recommendations to mitigate adverse relational, social and healthcare impacts of Covid-19 upon hospice services for vulnerable service users and those that care for them. The West Midlands region provides an ideal context in which to explore these issues, with its diverse community and broad demographic population served by 22 hospices. We will collate and provide an expert review of the grey evidence on Covid-19-associated service redesign that hospices in the region are producing. We will also produce in-depth understanding of the experiences of those involved in receiving and providing hospice care during the pandemic, and the determinants that are affecting this. We will use this evidence to quickly develop recommendations for local and national policy and practice. We will draw on our existing networks and collaborate with Marie Curie to develop a series of reports, delivered and disseminated throughout the project, to hospice service users, stakeholders, political leaders and civil society groups.",2021,-99,University of Warwick,298060.48,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health service delivery, +C09982,ES/W001845/1,Policing the Pandemic: The Role of Enforcement in Securing Compliance with the Coronavirus Regulations,"Compliance with the Coronavirus Regulations has been one of the most hotly debated topics of the pandemic. UK Police Forces were given unprecedented powers to enforce non-compliance with the Regulations, and yet there is a striking lack of robust evidence on the characteristics of those failing to comply with the Regulations. We know little about the reasons for their non-compliant behaviour, the level of risk they posed to the public or the impact of police enforcement. This project will conduct an in-depth examination of the factors and vulnerabilities underlying people's inability or unwillingness to comply and their Covid-19 testing and mortality outcomes. It will also explore police use of enforcement to secure compliance and the impact of this on individuals. Using a mixed method approach, it will provide insights from a unique database of Fixed Penalty Notices that were issued in Scotland, which will be linked at an individual level to a rich array of health, economic and social data within Scotland's Covid-19 Data for Research. It will also offer insights from interviews with individual offenders and police officers involved in the use of enforcement. The findings will be of significant interest and value to police officers, policy makers, and politicians across the UK in considering how best to encourage, enable, support or compel people to adhere to the Regulations as we encounter future waves of the current pandemic, and in any future public health (or other) emergency requiring some form of mass public compliance.",2021,-99,University of Edinburgh,488195.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C09983,ES/W001489/1,Real-time monitoring and predictive modelling of the impact of human behaviour and vaccine characteristics on COVID-19 vaccination in Scotland,"While COVID-19 vaccination will likely be transformative, however many uncertainties may influence how quickly and comprehensively vaccination will have an impact. We shall address here two interlinked factors: the potential for vaccinated individuals to transmit virus without displaying clinical symptoms, and the rate of vaccination uptake and how it may cluster in communities. We shall work with Public Health Scotland, to exploit real-time monitoring of vaccine uptake, COVID-19 testing and cases, to identify geographical localised impacts on infection rates. Wastewater surveillance data will help to identify possible shedding of vaccinated individuals by comparing detection rates before and after vaccination. Using an agent-based model fitted to cases across Scotland, we shall use these data to make short term forecasts for COVID-19 case numbers to support PHS planning. Long-term projections will consider vaccine-induced and natural immunity, vaccine refusal, logistics, and possible loss of immunity. An online survey will build on the ongoing OPTIMUM study by correlating vaccination attitudes and ease of access to Scottish demography, mapping these geographically via the Scottish index of multiple deprivation (SIMD). We shall use models of 'vaccination games' to consider possible future scenarios where combinations of hesitancy and refusal could cause higher refusal rates and embed these scenarios into our simulation models. We shall have a more refined understanding of COVID-19 epidemiology in Scotland under vaccination, and better predictions of epidemic trajectories to aid in planning, to inform possible stresses on hospitals and ICU, and to target vaccine deployment and information strategies. Our results will more generally inform relationships between vaccine attitudes and uptake and refine approaches to surveillance and control.",2021,-99,University of Edinburgh,361377.76,Human Populations | Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C09984,ES/W001985/1,Road to recovery:Understanding the impact of COVID and recovery phases on children and young people with Intellectual Disabilities and their families,"Intellectual disabilities (ID) are characterised by social, cognitive, and adaptive skill deficits (Zayac & Johnston, 2008), which are associated with challenging behaviours (Lee, et al., 2008), and communication difficulties (Memisevic & Hadzic, 2013). Elevated levels of mental health issues have been reported in young people with ID (Young‐Southward, et al., 2017) and their parents (Eisenhower et al., 2005). The COVID-19 response strategy entailed limiting access to education, respite care, and specialist services, reduced the available support for families, with unknown consequences. The relative vulnerability of children with ID was highlighted by a recent report by the Children's Society (2020) which indicated that children with ID are more susceptible to wellbeing and mental health issues as a result of COVID and require urgent support in adapting to routine changes and understanding what is going on. These routine changes and reduction in access to services will continue for some time despite the recent implementation of the UK wide vaccination programme, further compounding mental health outcomes in children with ID and their parents. As we move into COVID transition phase, the current project will: 1) identify the family structure and social demographics of families who have a child with ID who are at greater risk of parent and child negative mental health outcomes; 2) explore the lived experiences of CYP with ID and their caregivers during COVID and transition phases 3) understand the CYP's and parent's experience of the recovery phase, including the lasting effects of COVID.",2021,2022,University of Edinburgh,249543.92,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C09985,ES/W001764/1,Adapting offices to support COVID-19 secure workplaces and emerging work patterns,"COVID-19 changed where we work - 2019 5% of UK workforce worked mainly from home, reaching 44% in May 2020, remaining at 27% in July 2020 when restrictions eased (ONS, 2020). This multidisciplinary project supports economic recovery via identifying effective office design and adaptation of work practices to maximise gains and minimise downsides from remote and hybrid working. Homeworking offers flexibility and work-life balance, but most products and services result from collaboration and discussion (Elliot & Deasley, 2007) - work completion and performance are inherently social processes. Organizations must design offices, technologies and working practices that facilitate this social fabric. We apply a socio-technical approach to 1) establish exemplars for design and operation of offices adaptable to COVID-19 constraints, remote and hybrid working; 2) investigate how different office and work arrangements (e.g., hybrid working) impact social networks, workflow and performance by studying employees' in adapted offices (via interviews, high-frequency diary study, social network analysis, building data); 3) offer recommendations for supporting the transition of workers back into offices; 4) an evidence base to guide office requirement planning. Our project partners (WorldCC, Atkins, Leeds City Council, Coreus, Walker Morris, OneMedical Group) help us reach a range of industries and contribute data, advice and networks. We address:- UKRI RQs regarding COVID-19's impact on: (1) different organisations, sectors, and work patterns; (2) current and future demand for office space. POST's COVID areas of interest: (12.2) how will COVID-19 affect worker productivity in the future; (12.3) potential impacts for infrastructure of long-term widespread remote working.",2021,-99,University of Leeds,554593.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Economic impacts, +C09986,ES/W00173X/1,"COVID and the UK nations' fiscal frameworks: impacts, performance and lessons","The UK's devolved governments (UKDGs) have substantial policy autonomy over health, social care, business support and education and training, and hence are responsible for determining much of the policy response to the COVID-19 crisis for 10.5 million people. Their funding is governed by fiscal frameworks and settlements. These include a combination of grant funding, tax powers, and limited borrowing and other budget management tools. The COVID-19 crisis is an unprecedented health and economic shock that these frameworks were not designed for, demonstrating some strengths, but also revealing weaknesses. The UKDGs have articulated a number of particular problems. First are grant allocations, which take no account of economic or health needs, instead reflecting historic funding and changes in spending in England via the Barnett Formula. Second are strict limits placed on their own borrowing and reserves. Together, these mean that UKDG spending is constrained by English policy priorities, which may be inappropriate, especially if crisis impacts are assymetric. Moreover, these priorities have sometimes been poorly communicated, creating budgetary uncertainty. This project will address two issues. First it will consider how the current frameworks are affecting the UKDGs' ability to respond effectively to the COVID-19 crisis, taking account of the differential impact of it across the UK. Second it will appraise options for reform of these fiscal frameworks to enhance the capacity of devolved governments to support recovery from the pandemic. We will directly engage with governments, parliaments and other stakeholders to achieve these aims and inform key policy decisions.",2021,-99,University of Strathclyde,108714.68,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C09987,ES/W001993/1,School attendance among children with neurodevelopmental conditions a year after the COVID-19 pandemic,"The educational landscape changed dramatically due to the COVID-19 pandemic: school closures in 2019/20, compulsory return in September 2020 with measures to control infection, new regulations on COVID-19-related absences, low levels of school attendance in 2020-21 and increasing school de-registrations. Before the pandemic, school absenteeism was at very high levels among children with neurodevelopmental conditions (NDC). The pandemic has had multiple disruptive effects. We need to investigate how these effects might relate to school attendance in this vulnerable group one year after the COVID-19 pandemic started. Our project will investigate: - School absenteeism and reasons for absenteeism among children with NDC - Child, family and school factors associated with school absenteeism - Barriers and facilitators of school attendance - Parents' experiences of home schooling An online survey will collect data from approximately 1,500 parents of 5 to 17 year-old children with NDC across all 4 UK countries. Our focus will be on children with autism and/or intellectual disability, the most vulnerable children at high risk of adverse outcomes. We will recruit parents of: (i) children registered with a school in May 2021; (ii) children not registered with a school in May 2021 but who were registered with a school at the start of the pandemic in March 2020; and (iii) children not registered with a school on either date. Study findings will provide unique evidence on the impact of COVID-19 on school attendance and absenteeism, highlighting areas for improvement in educational policy and practice related to COVID-19 adaptations.",2021,2022,University College London,270282.72,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C09988,ES/W001810/1,Impact of Covid-19 on delivery and receipt of prison healthcare in the UK and implications for health inequalities: a mixed methods study,"We will produce robust evidence on the impact of Covid-19 on the delivery and receipt of prison healthcare in the UK, alongside an understanding of whether health inequalities have widened due to the pandemic. This will inform immediate clinical practice, commissioning and policy decisions at a regional and national level, in addition to providing planning UK wide recommendations for the recovery period. The application was written in response to the UKRI identified priority topic area ""social impact upon vulnerable groups: the prison population"". Our 12-month, mixed-methods study comprises three stages. First, we will undertake a scoping review of the literature to identify what is known already about Covid-19 and prison healthcare. Second, in a qualitative study we will interview 45 participants (people who have been in prison, prison healthcare staff and prison decision-makers) to explore their observations and beliefs about how and in what ways the pandemic has impacted on prison healthcare. Third, we will conduct an interrupted time series analysis to assess and compare change in recorded prison healthcare activity before, during and potentially after Covid-19. This analysis will utilise anonymised healthcare records from 13 prisons in England. The findings from all three stages will be formally integrated in a workshop. We will produce outputs for prison healthcare decision makers, clinicians, people currently or previously in prison and academics. Our well-connected team and existing prison healthcare research infrastructure means we can produce timely recommendations and directly influence national policy and practice as our findings emerge.",2021,2022,University of York,282074.09,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C09989,ES/W001780/1,Designing human resource management practices to improve the wellbeing of healthcare workers from BAME backgrounds in the context of COVID-19,"COVID-19 has disproportionately affected healthcare staff from BAME backgrounds. As the NHS is reliant on a diverse workforce, it is crucial to mitigate the impact of the pandemic on the wellbeing of BAME staff and thereby alleviate longer-term effects on service delivery and workforce planning. A current obstacle to achieving this successfully is a lack of understanding among healthcare organisations of how to design culturally appropriate and inclusive human resource management (HRM) practices that ensure BAME employees feel valued and supported. This study proposes to address this challenge by coordinating a series of tailored workshops, interviews and surveys in partnership with three NHS organisations. Surveys of BAME staff at all levels will investigate staff perceptions of organisational support, estimate their effects on wellbeing and identify areas of need. Targeted interviews with BAME staff will provide unique insights into critical experiences and impacts of COVID-19 on the BAME talent pipeline. Finally, a series of workshops will engage NHS managers, BAME networks and trade unions in co-producing HRM practices that target BAME staff wellbeing, progression and retention. Stakeholders will also co-produce a training framework and educational resources to raise awareness of BAME perspectives and wellbeing-oriented HRM practices. These will be piloted through the partner organisations and integrated into final deliverables. The project will lead to 1) a set of HRM practices and policy recommendations to transform the support being given to BAME employees and 2) an implemented training framework and educational resource pack for NHS managers and all staff.",2021,-99,"University of Leeds, Leeds University Business School",376398.1,Human Populations,Asian | Black | Other,Adults (18 and older),Unspecified,Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce, +C09990,ES/W001799/1,Influencing policy and practice through examining UK small business understanding of and response to COVID-19 regulation and guidance,"Regulations introduced due to the governmental response to COVID-19 force business leaders to take decisions with far-reaching consequences for employees' livelihoods, public and employee health, and the viability and survival of their businesses. Crucially, what underpins such decisions are complex judgements based on their understanding of the regulatory context and their capacity to discriminate between swathes of legal obligation and guidance of different kinds. This presents a particularly significant challenge to small businesses (0-49 employees) due to their constrained resources. The current pandemic represents the immediate context for this research, which will undertake a large-scale survey with follow-up interviews to understand how small businesses receive, understand and act on the UK's regulatory response to the pandemic and the financial, legal, and emotional costs of complying with this regulatory challenge. The UK regulatory context is further complicated by actions being taken at the level of devolved nations and regionalised variation of regulatory impact at different times. The research, in partnership with the FSB (Federation of Small Businesses), will provide evidence and insights to inform governmental regulatory responses to future public health crises and to regulation in a post-COVID landscape. It will arm those who formulate regulation and related guidance relevant to small businesses with greater clarity about the means by which businesses receive and interpret guidance, and whether and how they act on it. Regulation informed in this way has the potential to deliver a positive impact on employees' livelihoods, public and employee health, and the survival of UK small businesses.",2021,-99,Newcastle University,171695.58,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts, +C09991,ES/W001705/1,Developing a resilience framework and toolkit for UK creative micro-businesses as a route to recovery from the Covid 19 pandemic.,"The proposed work will design as well as assess the efficacy of a resilience framework and toolkit for creative micro-businesses (CMBs) across the UK as a way to aid in the creative sector's recovery from the Covid 19 crisis. Between May and December 2020, a survey of 322 creative and cultural organisations across the South West of England was conducted, led by Dr. Tarek Virani, and funded by the AHRC's Bristol and Bath Creative R + D Clusters programme. It showed that between 18% and 22% of organisations were either not affected by, or became more productive than prior to, the pandemic. Further and ongoing analysis shows a number of shared characteristics across these respondents. They are: diverse, smaller in size, have an online business model, able to pivot quickly, in collaboration with other sectors, engaging with support and anchor organisations, from a range of sub-sectors ( digital, hybrid and non digital), clustered in certain locations, and able to access some type of government support. Based on these findings, the proposed work seeks to: (1) develop a framework of resilience based on testing the accuracy of the above findings across the UK. This will be achieved by: First, distributing a survey to 1040 creative micro-businesses (CMBs) in nine city regions across the UK; second, analysing the survey results and then refining them further through a virtual focus group designed for a cohort of 90 CMBs from across the UK. The proposed work will then (2) design and test a resilience toolkit for CMBs based on the findings of the framework analysis. The toolkit will be presented, refined through a virtual focus group with the same CMB cohort, tested again (using a Randomised Controlled Trial) and then presented at a final resilience workshop. These outputs will aid the recovery and rebuilding of the creative sector across the UK.",2021,-99,University of the West of England,283586.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts | Other secondary impacts, +C09992,ES/W001772/1,Unmasking educational inequalities: The impact of COVID-19 on deaf students in higher education,"The global pandemic has had a significant impact on students in higher education and this has been well documented in the media, but the specific positon of deaf students continues to go unheard. This mixed-methods research conducted across England, Northern Ireland, Scotland and Wales, examines institutional responses to COVID-19 and the impact these responses had on deaf students' experiences. Institutional responses such as remote working, online teaching, facial coverings, online induction and extra-curricula activities will be explored. Deaf students' experiences of these measures will also be explored including any particular impacts on availability of human aids to communication such as interpreters, note takers, language support tutors, lipspeakers and sighted guides for deafblind people. It will examine availability and access to gateway assessment to support such as educational psychologists, disability assessors and the disabled students allowance scheme. The research will examine issues of inclusion and accessibility, in the online classroom and the wider organisations. It will explore perspectives and experiences of both new and returning students. It will examine institutional planning and responsiveness in the short, medium and longer term, but also in relation to future practices aimed at mitigating disadvantages experienced by deaf students so far. The research seeks to make recommendations for supporting current students in the remaining part of their studies. Given the current calls to re-think HE provision (Hack, 2020) the project will also make best practice recommendations for teaching deaf students online in the longer term. Deaf student voices will be centralised in any recommendations presented.",2021,-99,University of the West of Scotland,341913.59,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C09993,ES/W001950/1,Mitigating the impact of COVID-19 disruption on the quality and retention of trainee and newly qualified secondary school teachers,"This project documents the impact of the substantial changes and sustained disruption caused by COVID-19 to the development of secondary school teachers, during their training and newly qualified teacher (NQT) years, and will produce a set of recommendations to enhance teacher quality and retention. Failure to respond now means that 60,000 teachers, working in secondary schools across the UK, will not have sufficient expertise and may rapidly leave the profession. This lack of expertise and high attrition will have a serious impact on the educational outcomes of young people who have already faced significant disadvantage through school closures and ongoing COVID-19-related disruption. Findings from a pilot study underline the extensive challenges facing trainee and NQT teachers and the future learning that needs to be urgently addressed by the Initial Teacher Training (ITT) sector. This project will produce research-informed recommendations that will mitigate COVID-19-related disruptions on teacher quality and retention. Research findings will be generated through analysis of responses gathered from questionnaires and remote interviews with trainees, NQTs, school leaders, and ITT staff based in both schools and university, based on a sample of 400 teachers trained at King's College London (KCL). The project timeline includes interviews across 18 months so that participants' experiences are captured during both the training year and the first year of practice as an NQT. This will provide rich understandings of the impacts of COVID-19 on teacher quality and retention that will have relevance for policy makers, school leaders and ITT providers across the UK.",2021,-99,King's College London,249056.03,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C09994,ES/W001306/1,The Coronavirus Job Retention Scheme and Employer Perceptions of Part-time Working: the implications for economic recovery and future working,"Covid-19 has caused a severe shock to the UK economy, with the highest level of unemployment since the 1980s predicted (Office for Budget Responsibility). Part-time working is increasingly, and internationally, recognised as an alternative to unemployment in a recession, avoiding the costs of benefit payments, loss of tax receipts and some social and health costs of unemployment, whilst retaining skills in the economy. Despite demand from employees, particularly certain demographics, employers have often perceived part-time working as costly and inconvenient, struggling to create quality part-time jobs. The Coronavirus Job Retention Scheme's (CJRS), 'flexible furlough' provision allowing employees to work part-time and be part-time furloughed, has effectively been an experiment in part-time working for many employers. This research is designed to examine employers' experiences of using part-time working under this scheme and whether this has changed their perceptions of its feasibility. Conducting semistructured interviews with managers from selected sectors at two time points, together with a large-scale, representative survey, the research seeks to understand employer responses and whether their perceptions and practices have changed. The findings will have implications for government policy relating to the role of part-time working in the economic recovery and the encouragement and support government needs to provide for employers. The research will be carried out in collaboration with the Confederation of British Industry (CBI), to enable data collection from a large number of UK employers (c. 20 000) and facilitate impact, together with a Steering Group with membership from professional organisations and government.",2021,-99,Cranfield University,345801.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C09995,ES/W001691/1,An investigation into the experiences of domestic abuse helpline staff and service users during COVID-19 lockdown,"Mobility restrictions enforced by the UK Government in March 2020 as a response to COVID-19 resulted in those vulnerable to domestic abuse (DA) being confined in isolation with their abusers, deprived of safe spaces or opportunities for help or support. This saw a spike in engagement with domestic abuse helplines (DAH) during lockdown. However, little is known about the nature of these calls, the experiences of service users during lockdown, or the impact of this surge on DAH staff. Three data collection phases will address this. Remote interviews with DAH staff (n=15; Phase-1) will be analysed narratively and thematically, identifying patterns in the nature of calls received, impact of increased demand on the wellbeing of DAH staff, and emerging support needs. Simultaneously, a survey will be distributed to DAH service users (n=200; Phase-2) investigating the impact of lockdown on the instance and severity of abuse, the impact of/on others in the home and mental health and wellbeing outcomes. Results will be analysed using frequency analysis, inferential statistics and content analysis. Service users will be invited to engage in a final wave of remote interviews (n=15; Phase-3) to provide more in-depth elaboration on survey responses and elicit views regarding ongoing support requirements. We have confirmed involvement from 5 DA helplines (see section 1.4). These three phases are critical to understanding the lived impact of lockdown on DAH staff and service users. Findings will act as a crucial guide for policy decision-making regarding support needs emerging from the pandemic and beyond.",2021,-99,University of the West of Scotland,46056.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts, +C09996,ES/W001829/1,Impact of COVID-19 on family carers for profound and multiple learning disabilities (PMLD): Development of a support programme.,"There is a dearth of research on the impact of COVID-19 amongst families of people with profound and multiple learning disabilities (PMLD) and yet 59% of all COVID-19 deaths in England and Wales have been among people with disabilities (1). A recent 2020 study indicated that people with learning disabilities aged between 18-34 years are 32 times more likely to die of COVID-19 compared to the general population (2). We have chosen to focus on PMLD as an exemplar condition of people with severe disabilities as they comprise the most vulnerable population. The vulnerability of this group is exacerbated by a reduction in services at a time when needs have increased (3). A survey by Carers UK suggests that 4 out of 5 carers are now providing more care for their relatives (3). While an effective vaccine may have been discovered, the reduction of services during the pandemic may mean that the future of social care for these families is uncertain and subject to change in the longer term. We propose to ask family carers (n=180) from across the UK and Ireland about their experiences and will then use this new learning to co-design a tailor-made support programme. We will do this by means of online focus groups with stakeholders using questions which have been co-designed with carers and our voluntary sector partners. The subsequently developed online programme will be tested for acceptability employing mixed methods and will be implemented across the UK and Ireland.",2021,-99,Queen's University Belfast,375666.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C09997,ES/W00156X/1,Optimising Covid-19 diagnostic Testing Systems (OCTS): An international comparative study of diagnostic innovation and learning,"This study asks how leading countries are organising and using national and regional diagnostic testing systems for Covid-19 ('testing systems') in order to reduce Covid-19 mortality per capita in their populations, to avoid or shorten 'lock-downs', and reduce economic impacts from the pandemic. We will explain how testing systems have been shaped during the pandemic, and how challenges related to testing are overcome. The research will span North America, Europe, Africa, Asia and Australia as well as the UK. The project builds on an established Covid-19 UK research and knowledge exchange hub at the University of Sussex that has been facilitating rapid dialogue and dissemination of research on Covid-19 diagnostic testing between the international research team and policy makers in the UK and beyond. The hub has a track-record of reporting results that have been widely welcomed and valued by the UK civil service and reported widely to public audiences in the media. As the pandemic continues, understanding the use of testing systems remains vital to optimise the Covid-19 response and save lives. With innovation and learning continuing (e.g. around the UK government's ambitious mass-testing programme), we propose to undertake further comparative research to share lessons across contexts. In order to support Covid-19 responses internationally, we will engage with governments and share deliverables from the early months of this 15-month project. Additionally, to inform preparations for future outbreaks and pandemics, we will contribute to national and international fora seeking to learn lessons from the current crisis.",2021,-99,University of Sussex,828545.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions, +C09998,ES/W000601/1,Increasing rail transport throughput while avoiding incentives to compromise social distancing: agent-based quantification leading to guidelines,"Public transport is crucial to economic activity, functioning cities and access to work, but presents many pinch-points (doors, confined areas of queuing, ticket gates) where social distancing is easily compromised. These points determine people flow rates, creating conflicting priorities in enabling functioning transport while maintaining social distancing safety. Research is proposed building on previous agent-based modelling of passengers at the railway platform-train interface conducted using massively parallel Graphics Processing Unit (GPU) simulations for parameter exploration and sensitivity analysis. Our current RateSetter model has informed rail sector policy and stakeholders through collaboration with Railway Safety and Standards Board (RSSB). Additional factors to be explored include: (i) Incentives such as imminent train departure to compromise social distancing. (ii) Limitations on personal situational awareness in complex confined space pedestrian flows. (iii) Differing personal assertiveness and its impact on confined space flow dynamics. Modelling will focus on optimisation of passenger flow to avoid incentivising compromised social distancing, providing guidelines on effective timetabling and COVID safe station operation. RSSB will facilitate data access, knowledge exchange and dissemination within the rail industry. The work will increase confidence in rail use and enable higher passenger volumes with lower risk of compromised social distancing through: (i) Algorithms representing human movement in confined spaces subject to incentives to compromise social distancing. (ii) A validated model to rapidly test and optimise new ways of operating transport to aid national recovery. (iii) Guidelines on quantification of intervention effectiveness in limiting proximity and cumulative proximity (potential viral load) for passengers and staff.",2021,-99,University of Sheffield,215525.06,Other,Not applicable,Not Applicable,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Impact/ effectiveness of control measures, +C09999,BB/W003260/2,The role of short ACE2 in Sars-CoV-2 infection and patients susceptibility to COVID-19,"The virus responsible for COVID-19, SARS-CoV-2 utilizes a protein on the surface of cells named Angiotensin Converting Enzyme II (ACE2) as an entry gate. The presence and amount of ACE2 on specific cells is largely responsible for the ability of the SARS-CoV-2 virus to infect cells in the human body. It is therefore of critical importance to study how ACE2 levels vary in different cells and individuals, especially in categories at risk for COVID-19, to understand how this could affect their predisposition to infection and disease severity. We recently discovered that airway cells express a second form of ACE2, which we named short ACE2, in addition to the previously known, long form of ACE2. This novel short ACE2 does not appear to allow virus entry because it lacks regions involved in virus interaction. Surprisingly, we also discovered that short ACE2 is the main form produced in response to Interferons (IFNs); molecules released from cells of the immune system in response to viral infections to protect our tissues. These discoveries made clear that there is an urgent need to better understand the pattern of long and short ACE2 expression in cells and how this varies in patients. Since short ACE2 is IFNs-regulated, and it is not competent for SARS-CoV-2 entry, we reason that it might be part of a mechanism for protecting airway cells from SARS-CoV-2 infection. In this proposal we will study the levels of short and long ACE2 in different cells and patients to correctly understand the relationship between ACE2 levels and susceptibility to infection from SARS-CoV-2. In particular, we will study patients at particular risk of infection to COVID-19 such as Black, Asian and Minority Ethnic (BAME) patients, and patients with severe respiratory diseases such as COPD. To better understand the function of short ACE2 and its potential role in protecting cells from viral infection, we will generate cellular models including human airway cells lacking or having an excess of short ACE2 to investigate its effect on SARS-CoV-2 infection. This study will generate critical information about the interaction between the virus and different cell types in the lung. Importantly it will help identify why some people are more susceptible to SARS-CoV-2 and offer insight into novel therapeutic possibilities targeting short ACE-2; ones aimed at reducing viral transmission and COVID-19 disease severity.",2021,-99,MRC Toxicology Unit at the University of Cambridge,,Human Populations | Other,Asian | Black,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis", +C10000,BB/V018922/1,Human ACE2 transgenic pigs: A large animal model for Covid-19,"Animal models which accurately reflect Covid-19 disease will be critical for vaccine development, antiviral testing and pathogenesis studies. Successful application of in vivo studies will depend on a combination of approaches from multiple animal models. There are a number of animal models for studying Covid-19. Rodent models, including aged mice, mice engineered to express hACE2 and mice infected with mouse adapted virus, have all been used. Golden Syrian hamsters are also susceptible to human coronaviruses. Ferrets are susceptible to infection and have shown promise as models of viral spread. Non-human primates are the most comparable model to human infections. While each of these models has advantages, there are also drawbacks. Rodent models do not accurately reflect human disease and their gross morphology and immunological responses are divergent from humans. Ferrets lack molecular tools, while non-human primates are expensive and restricted to a few institutions around the world. There is a growing appreciation of the use of livestock species as models for human disease. We propose developing pigs as large animal models for Covid-19. Their use is less restrictive compared to non-human primates and associated molecular tools are improving rapidly. As pigs are not susceptible to SARS-CoV-2, we will generate transgenic pigs that express the human angiotensin-converting enzyme 2 (ACE2), the main receptor for SARS-CoV-2 and main determinant of species susceptibility. As well as being an excellent model for vaccine development and antiviral testing, a viable pig model of Covid-19 would be extremely valuable to answer important questions of viral pathogenesis such as; which cells, tissues and organs are infected and when? How does the virus spread within the body? Does the virus infect the central nervous system and what are the long-term consequences of cardiovascular involvement? What factors effect spread between hosts? These studies will not only be critical in our ability to successfully respond to the current pandemic, but will be important for our ability to respond to future pandemics.",2021,2022,University of Edinburgh,377282.14,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +C10001,BB/V017780/1,Development of a virus-free sensor system to repurpose approved drugs for blocking Coronavirus replication,"The COVID19 pandemic has highlighted the importance of timely discovery of antiviral therapeutics, especially when there is little information as to whether vaccines developed (and pending approval) enable a significant period of immunity. Therefore the development of cost effective, high-throughput sensor systems to rapidly repurpose approved drugs as antiviral agents is extremely desirable. We have developed a virus-free sensor system - pShiftSensor that can specifically screen for drugs to block SARS-CoV2 replication by inhibiting the ribosomal frameshift that is essential for production of the viral replicase. The sensor system is fluorescent-based, therefore permitting cost-effective high-throughput quantitate readout. The system is based on the cis-element required for -1 programmed ribosomal frameshifting (-1 PRF), a non-canonical translation mechanism that is ubiquitous throughout all coronaviruses and used to synthesis viral proteins including the RNA-dependent RNA polymerase (RdRP), essential for viral replication. We have developed pShiftSensor-v1, which is a dual-reporter system that contains the SARS-CoV-2 -1PRF cassette (i.e. the slippery sequence UUUAAAC and the 3' pseudoknot). The system is bi-cistronic thereby avoiding expression artifacts due to differential delivery between the control and test reporter expression cassette. Through this proposal, we will upgrade our system to pShiftSensor-V2, which targets primary cell types such as small airway lung cells, the key entry cell type for SARS-CoV2 infection, and primary leukocytes, especially monocytes/macrophages and T-cells, essential for systemic infection. pShiftSensor-V2 will permit cost-effective, high-throughput cell-type specific screening of viral replication inhibitory compounds in a physiological environment.",2021,2022,University of Cambridge,327268.55,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C10002,MR/W005611/1,G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation,"SARS-CoV-2 has caused 1.4 million deaths and has devastated economies worldwide. As SARS-CoV2 replicates and spreads, its RNA genome inevitably mutates. Mutations may confer altered properties of potential concern to human health, such as increased pathogenicity or transmissibility, or reduced sensitivity to prior immunity or antiviral drugs. Importantly, the imminent roll out of vaccination campaigns could provide strong selection pressure for escape from vaccine-induced immunity. We are a consortium (""G2P-UK"") of UK virologists who will work openly with COG-UK and UK-CiC, to establish an experimental pipeline and shared resources (reagents, methodologies and model systems) to rapidly define the phenotypic impacts of SARS-CoV-2 mutations as they emerge. With three interconnected work packages we will obtain and distribute clinical isolates and engineered SARS-CoV-2 mutants (WP1), test the functional properties of the mutations in in vitro assays (WP2) and characterise their phenotype in culture and animal model systems (WP3). The choice of strains and mutations will be informed by a joint working group that includes COGUK members. Current virus strains will be immediately introduced into the pipeline, to accumulate a baseline of underpinning knowledge about SARS-CoV-2 behaviour, to validate the consortium working relationships and to seed mechanistic studies suitable for further research. Then, as variants of concern are detected, they will be prioritized for co-ordinated investigation in real time. By interpreting the biological consequences of SARS-CoV-2 mutations we will inform on the associated risks and vulnerabilities related to public health policy and clinical practice, including treatment strategies, diagnostics and infection control, and vaccination.",2021,2022,Imperial College London,3471149.7,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Pathogen morphology, shedding & natural history | Disease models",2021 +C10003,MR/W004798/1,Neurophysiological characterisation of post-COVID fatigue,"Despite the high severity of the SARS-CoV-2 virus in a substantial minority of those infected, most people only suffer from mild initial symptoms, which typically resolve without the need for hospitalisation. However there is increasing evidence that longer term neurological sequelae can occur even after mild disease, and of these, fatigue and muscle weakness are reported with a high incidence (typically >20%). Although fatigue can be a non-specific core symptom associated with many different conditions, its detrimental impact on quality of life and productivity is well established, particularly if it develops into a chronic symptom. As a novel disease, the mechanisms behind the impact of COVID on neural function remain unclear and this is particularly so for post-COVID fatigue (pCF). Our aim is to use observational and electrophysiological methods to characterise the neural mechanisms behind pCF, particularly with respect to the sensorimotor system and to monitor their progression over time. Even after this pandemic is brought under control, by whatever measures develop over the coming months and years, the longer term sequelae will continue to reap a substantial cost both to the individuals but also to the economic recovery of the nation as a whole. By understanding the neural mechanisms of pCF we can understand the epidemiology better and make more rational decisions for interventions and treatments.",2021,2022,Newcastle University,300873.84,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C10004,MR/W002663/1,COV-AD: COVID infection in patients with antibody deficiency,"Our national case series has found that individuals with primary and secondary immunodeficiencies are more likely to develop severe COVID-19. Individuals with immune deficiency respond poorly to some vaccinations and concern has been raised suboptimal immune responses may allow viral persistence, accelerated viral evolution and the emergence of viral escape variants that may potentially pose a public health risk. Understanding the immune response to the SARS-CoV-2 virus following natural infection or following vaccination is, therefore, of the upmost importance in individuals with immune deficiency. This multicentre study, involving a network of Clinical Immunology centres across the United Kingdom, will recruit 1050 individuals with antibody deficiency to study the magnitude and quality of their immunological responses following natural infection with SARS-CoV-2 and/or their response to vaccination. In partnership with the SavingLIVES charity, individuals will be invited to submit swabs and dried blood spots which will be tested for the presence of the virus and the presence of antibodies against the SARS-CoV-2 spike glycoprotein respectively. Serial swabs will be used to understand the prevalence of persistent viral infection in individuals with antibody deficiency and this information will be correlated with symptom diaries the spectrum of disease in patients with antibody deficiency. PCR positive samples will be submitted to the UK COG consortium for sequencing and phylogenetic analysis. Separate study arms will examine whether patients with immune deficiency make antigen specific antibody and cellular responses to the virus following natural infection or vaccination. This study will provide valuable insight into how SARS-CoV-2 infection manifests in immunologically vulnerable individuals and inform on whether public health countermeasures including vaccination are likely to be successful in preventing infection and disease in this population.",2021,2022,University of Birmingham,1105378.04,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2021 +C10005,MR/V035401/1,MICA: Community Based Point-of-Need Integrated Diagnostics for SARS-CoV-2,"Currently, validated diagnostic tests for SARS-CoV-2 infections include laboratory-based tests involving Reverse Transcriptase (RT) Polymerase Chain Reaction (PCR) or RT-isothermal Loop-Mediated Amplification (RT-LAMP), using swabs from the upper respiratory tract, as well as blood-based IgM/IgG/IgA enzyme-linked immunosorbent assays (ELISAs). Rapid diagnostic tests (RDTs) lateral flow immunodiagnostic devices (LFD) are also available for community testing. Most recently DNA testing ex-laboratories has been achieved, albeit with complex and expensive units (e.g. DNAnudge). In general, although these commercial products provide solutions for testing in many scenarios, there remains a need for low-cost, point-of-need nucleic acid sensors, able to detect SARS-CoV-2 infections in a timely manner, providing multiplexed tests (e.g. with RSV, influenza), without the need for expensive equipment. We have developed a novel SARS-CoV-2 LAMP assay, targeting sequences in the ORF1 ab region and N gene simultaneously (as recommended by China CDC and USA FDA). The assay has been optimised, now giving a limit of detection <64 copies/ml and validated clinically against 7 other respiratory viruses, showing no cross reactivity. We propose to incorporate this into a multiplexed community-use, hand-held nucleic acid-based sensor as a self-contained single-use disposable device. A nasopharyngeal swab or saliva sample will be placed into an injection-molded cartridge, containing all reagents to perform sample enrichment and RT-LAMP. The multiplexed result is read visually on an integrated paper-LFD. The device enables (i) sample enrichment, reducing the elution volume from a swab and (ii) simple methods for thermal management, and will be validated in a statistically-powered study, to ensure the test's rapid translation to our clinical and industrial partners.",2021,2022,University of Glasgow,526023.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C10006,MR/V041533/1,Primary Care response to DVA in the Covid-19 pandemic,"Aim To understand the impact of UK-wide COVID-19 social isolation policies on domestic violence and abuse (DVA) in the context of the general practice response during the pandemic and its aftermath, Research questions 1. What is the impact of COVID-19 social isolation policies on referral to specialist DVA support for patients experiencing abuse? 2. In remote consultations, how have GPs managed asking about/identifying abuse, giving support and offering referral to patients experiencing DVA amd how have they adapted to online DVA training? Methods Question 1: Interrupted-time series (ITS) and non-linear regression analysis including sensitivity analyses, using practice level referral data across 30 areas. Incidence rate ratios (IRR) and 95% confidence intervals of changes in referral rate before, during and reversal of social isolation policies, quantifying the impact of these COVID-19 prevention policies on DVA referrals. The analysis will cover one year before and one year after the implementation of social isolation (23/03/2019 - 22/03/2021) and the sudden national shift - for at least part of the second period - to online GP consultations. Question 2: Observation and interview-based qualitative study in a purposive sample of practices by ethnic and SES of population, and referral rates. Sampling of 30 GPs within selected practices and 10 other professionals (practice managers, DVA advocate educators); observation of 10 online training sessions. Thematic analysis. Triangulation of ITS with qualitative findings, exploring variation in the referral rates between areas, rapidly reporting relevance, feasibility, and safety of GP responses to DVA during the COVID-19 pandemic and its aftermath.",2021,2022,University of Bristol,184127.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10007,EP/W000032/1,"Analysing group testing algorithms for COVID-19 surveillance and case identification in UK schools, universities, and health and social care settings","In the context of a pandemic disease such as Covid-19, group testing (also known as 'pooled testing' or 'batch testing') provides a way of identifying infected individuals in a large group, by pooling samples together in different ways and testing the pooled samples. Group-testing algorithms can yield large efficiency gains over individual testing, when the number of infected individuals (i.e., the prevalence) is relatively low. This project will analyse whether and how strategies based on group-testing algorithms may be effectively used for monitoring Covid-19 prevalence, and for case-identification (i.e., screening of asymptomatics to identify infected individuals), in UK schools, universities, care homes and health care settings. Close attention will be paid to all the practically relevant issues: the impacts on public health and education-loss, resource requirements/costs, the practical ease or difficulty of implementing different strategies in situations of changing (and geographically varying) prevalence, the feasibility of incorporating a pooling step into existing UK testing systems, and ethical/anonymity requirements. As well as producing technical preprints and papers, we will produce non-technical reports aimed at policymakers and written in a way accessible to those without mathematical or scientific training, to aid decision-makers in determining which protocols to implement. Our initial focus will be on schools and universities, and later we will extend our study to health and social care settings.",2021,2022,University of Bristol,118643.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C10008,EP/V055372/1,How simple plastic surfaces can be recruited to the fight against contact transmission of SARS-CoV-2,"To date, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) appears to spread easily in droplets in the air and via surfaces. Early work indicates that viruses appear to remain infectious longer on some surfaces compared to others. However, it is currently unclear what role the surface chemistry plays in the survival, infectivity and denaturation process of the virus outside a host on surfaces. Simple polymers, on which the surface chemistry reduces the transfer of infectious viruses in the ambient environment, would have the advantage over the currently available active-loaded and protein-coated products which deplete and degrade over time. The aims of this project are to identify the effect on the virus adsorption, infectivity and denaturation behaviours of; 1) a range of commercially available gloves and other PPE surfaces, e.g. visors, to enable a recommendation of which existing polymers should be employed for optimal PPE, and 2) screen novel polymer surfaces using high throughput methodologies for selection of virucidal performance recently developed at the University of Nottingham, to develop new polymers for PPE and contact transmission control. Objectives: 1. Quantify viral binding and inactivation under ambient conditions to existing PPE plastics. 2. Quantify the magnitude and specificity of SARS-CoV-2 virus-like particle (VLP) or SARS2 spike-containing pseudovirus (PV) binding to polymers using libraries presented on micro arrays. 3. Quantify the adsorption, infectivity and denaturation of SARS-CoV-2 viruses bound to the scaled up 'top 10' polymers of interest on slide or multiwell-plate and other PPE materials (using new facility in Nottingham). 4. Develop anti-SARS-CoV-2 polymers for PPE and more widely for infection protection control surfaces.",2021,2022,University of Nottingham,574263.21,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Pathogen morphology, shedding & natural history | Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2021 +C10058,unknown,REACT long COVID (REACT-LC),"This project aims to characterise and better understand the genetic, biological, social and environmental signatures and pathways of long COVID. It will also identify factors affecting why some people experience long term health effects of COVID-19, while others do not. To date, most research on long COVID has been in hospitalised patients. The researchers will survey 120,000 people in the community who have taken part in the REACT study. Over 30,000 participants from REACT who tested positive for COVID-19, plus 90,000 who tested negative, will be invited to take part. Participants will be sent a survey about their health, symptoms and experiences. Participants with long COVID will be asked to join a panel to provide regular updates; while 60 will be invited for in-depth interviews. The researchers will develop a set of patient-reported outcomes that reflect the symptoms most important to people living with long COVID in the community. Researchers will also invite up to 8,000 people with positive tests, including at least 4,000 with long COVID, for health tests and samples to test for genetic and other biological markers. This will help researchers understand mechanisms causing persistent symptoms and may point to possible treatments.",2021,-99,Imperial College London,7506000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Post acute and long term health consequences, +C10059,unknown,"Therapies for long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)","This project aims to identify which treatments are most likely to benefit people with particular symptoms of long COVID and test supportive treatments to improve their quality of life. The researchers will identify around 2000 patients with long COVID from GP records. Study participants will be invited to use a digital platform to report long COVID symptoms/quality of life. A subgroup of around 300 patients will receive blood and other biological tests to understand the immunology of long COVID and will wear a device that will measure their heart rate, oxygen saturation, step count and sleep quality. The researchers will review evidence for long COVID treatments, including drugs or supportive interventions (e.g. for mental health or tiredness). Working with patients, doctors and other experts, the researchers will recommend treatments that should be tested in long COVID patients and co-produce a targeted intervention for long COVID, tailored to individual patient need. This will be delivered remotely in the community, via the Atom5TM app, providing critical support and information to empower patients in self-managing long COVID. In addition, they will provide tailored resources to support symptom management and nurse-led support for those with the severest symptoms. The researchers will also use the digital platform to assess whether the treatments and supportive interventions reduce symptoms, improve quality of life, and are good value for money.",2021,-99,University of Birmingham,3197000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Post acute and long term health consequences, +C10060,unknown,"Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services","This project aims to provide an evidence base for healthcare services to define what long COVID is and improve diagnosis. It will address why some people get the condition, the typical effects on a person's health and ability to work, and the factors which affect recovery. It will also look at how best to ensure patients are able to access the right treatment and support through health services. The researchers will use data from more than 60,000 people drawn from a combination of national anonymised primary care electronic health records and longitudinal studies of people of all ages across the country. From these studies, people reporting long COVID and comparator groups, will be asked to wear a wrist band measuring exercise ability, breathing, and heart rate. Participants will also complete online questionnaires on mental health and cognitive function. They will also be invited to a clinic for non-invasive imaging to look at potential damage to vital organs, such as the brain, lungs and heart. Findings will be shared with bodies involved in clinical guidelines (NICE, as collaborators in this project), with government (via the Chief Scientific Advisor), with the public via social media and other outputs, and the scientific community via research publications",2021,-99,University College London,13344000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts, +C10061,unknown,Non-hospitalised children and young people with long COVID (The CLoCk Study),"This research project aims to characterise symptoms typical of long COVID in non-hospitalised children and young people. It will also assess risk factors, prevalence and how long it lasts. This research will establish a medical diagnosis and operational definition of the condition, and look at how it might be treated. The researchers aim to enrol 6,000 children and young people in the study, in two equal size cohorts - consisting of 3,000 who have had a positive COVID-19 test, and 3,000 who have not. Participants will be asked whether they still have physical or mental problems at 3, 6,12 and 24 months afterwards infection. Comparisons will then be made between the two cohorts. Carers and children and young people taking part will be involved in co-production of this study, and encouraged to complete surveys. Results will be published, used to inform NHS services and health policy - and made available to participants. The study will provide data to help doctors to diagnose long COVID, establish how common it is, risk factors, and how long it goes on for",2021,-99,"University College London, Great Ormond Street Hospital",1946000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts, +C10062,unknown,Understanding behaviour and spread of COVID-19 in the UK,"The team will collect samples and data from COVID-19 patients in the UK to answer many urgent questions about the virus in real time, such as: who in the population is at higher risk of severe illness what is the best way to diagnose the disease what is happening in their immune systems to help or harm patients how drugs behave in people with the infection how long people are infectious for and from which bodily fluids whether people are infected with other viruses (e.g. flu) at the same time. The study will recruit at least 1,300 UK patients over the next year and aim to start communicating their initial results in months. The team's capacity builds on planning over the past 8 years as part of the International Severe Acute Respiratory Infection Consortium, and it includes co-investigators from six UK universities and Public Health England.",2021,-99,"University of Edinburgh, Imperial College London, University of Liverpool",5635000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C10063,unknown,Developing processes to manufacture vaccines at scale,"The team is aiming to develop manufacturing processes for producing adenovirus vaccines at a million-dose scale, so that - if clinical trials are successful - a vaccine could be made available to high-risk groups as quickly as possible. They are working with Professor Sarah Gilbert's team, who are developing promising novel coronavirus vaccines by modifying harmless adenoviruses.",2021,-99,University of Oxford,460000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies, +C10064,294011,COVID Oximetry @ home (CO@h): A rapid patient experience study,"During the first wave of the COVID-19 pandemic, some patients were not admitted to hospital until they were displaying advanced symptoms of COVID-19. These patients may then have received invasive treatments and/or been admitted to intensive care. Monitoring patients at home may help to reduce these delays and identify patients earlier. In the UK, a healthcare service called COVID Oximetry @home has been nationally rolled out by NHS England. Within this service, patients are given an oximeter and asked to record their oxygen levels regularly. Patients are monitored and sent for further care if problems arise. This research aims to explore patient experiences of receiving and engaging with the COVID care at home. To find out about how patients and staff have experienced COVID care at home, we will do two things. a) First, we will conduct a national survey with patients and carers in as many NHS trusts across the country as possible. The surveys will explore patient experiences of receiving and engaging with COVID care at home. We will analyse this data using descriptive statistics (e.g. percentages). b) Secondly, we will carry out some case studies in 12 selected NHS sites. We will speak with patients who have received COVID care at home, or who have withdrew from receiving care or declined care. These interviews will help us to find out more about how people experienced receiving COVID care at home and the things that help or get in the way. This research is important as it will help us to find out if healthcare services that require patients to monitor at home are effective, affordable and suitable and practical for both patients and healthcare professionals.",2021,-99,University College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management", +C10065,249030,BASIL+: Behavioural Activation for Social IsoLation,"Summary: This study is based on an existing programme of research, the Multi-morbidity in Older Adults with Depression Study (MODS) which aims to establish if a new treatment for depression in people with long term physical health conditions is effective and good value for money. It focuses on older adults who have minor depression and two or more long-term physical health problems (i.e. diabetes, asthma, heart-disease).For phase1 we first developed a new treatment by talking to older adults with experience of low mood symptoms and physical health problems, and to caregivers and health care professionals. From the understanding we got from these conversations we adapted training and treatment materials used in previous depression studies. We then conducted group discussions with a range of older adults and caregivers, health care providers and academic experts. From this set of materials a short programme (Behavioural Activation) was developed and delivered to around 10 patients recruited from GP practices. We then conducted interviews with patients and health care professionals to further develop materials for use in phase 2. Phase 1 resulted in the short treatment programme (Behavioural Activation) which was given mostly by telephone (with face to face contact for the first session) in late 2019. In March 2020 all older people with multiple health conditions were instructed by the UK government to follow social distancing/isolation guidelines. In response to this, the MODS programme team have amended the Behavioural Activation treatment programme developed in phase 1. The Behavioural Activation in Social IsoLation (BASIL-C19) pilot study aims to test whether this amended treatment programme could be offered to older people with long term conditions to help deal with depression and loneliness during the period of Covid-19 enforced isolation. Description: This study is part of the MODS (Multi-Morbidity in Older adults with Depression Study) programme, which is looking at whether a talking treatment called Behavioural Activation (BA) can help improve a person's physical and psychological functioning, for example self-care and mood. The first workstream of the programme completed in December 2019, and in response to COVID-19 the study team have made specific adaptations to their intervention to answer the following question, 'can we prevent or ameliorate depression and loneliness in older people with long term conditions who are under enforced COVID-19 isolation?'. This is a pilot study which will be recruiting in primary care. Eligible and consenting participants will be randomised to either the intervention group or the usual care group following completion of a baseline questionnaire.",2021,-99,"Tees, Esk and Wear Valleys NHS Foundation Trust",,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10067,282127,Neonatal Complications of Coronavirus Disease (COVID-19) Study,"Summary: This study will collect information about newborn babies admitted to hospital who have Coronavirus (COVID-19) or who are born to mothers who have COVID-19 and require hospital care. The information we collect will help us to understand: how babies get COVID-19; what happens to babies when their mother has COVID-19; what treatments are effective in helping babies with COVID-19 to get better; and what happens to babies when they have been treated. We are carrying out the study through a system called the British Paediatric Surveillance Unit (BPSU): www.rcpch.ac.uk/work-we-do/bpsu Each week every doctor across the UK looking after newborn babies in hospital will be asked by the BPSU if they have looked after a newborn baby with COVID-19 or whose mother has COVID-19. If they have, they will be sent a questionnaire to collect information about the baby and their mother. This identifiable information will be shared with us under special temporary provisions introduced in England & Wales by the Secretary of State for Health and Social Care to allow the processing of confidential patient information without consent for COVID-19 public health, surveillance and research purposes during the current pandemic. [Study relying on COPI notice] Description: Coronavirus is a new virus that has come from China where it was first recognised as a causing a new infection (COVID-19) in late 2019. So far we have very little information about how the virus affects mothers and newborn babies and it is not clear how best to care for mothers and babies affected. We have very little information about how babies get Coronavirus infection, whether it transmits from mothers to their baby(s) while they are still pregnant, during labour and birth, or whether the infection occurs following birth. Understanding this will mean that we can give the best care to mothers and babies and the best advice to pregnant women about the effects of Coronavirus on their baby. This study will collect information about newborn babies who have Coronavirus or who are born to mothers who have Coronavirus. Thw information we collect will help us to understand: • How babies get Coronavirus • What happens to babies when their mother has Coronavirus • What treatments are effective in helping babies with Coronavirus to get better • What happens to babies when they have been treated We are carrying out the study through a system called the British Paediatric Surveillance Unit (BPSU) www.rcpch.ac.uk/work-we-do/bpsu. Each week every doctor across the UK looking after newborn babies in hospital will be asked by the BPSU if they have looked after a newborn baby with Coronavirus or whose mother has Coronavirus. If they have, they will be sent a questionnaire to collect information about the baby and their mother. As this information is needed very urgently about all affected babies we will not be asking parents for consent to include their baby's information in the study, although parents will be able to opt out.",2021,-99,University of Oxford,,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,"Disease transmission dynamics | Disease pathogenesis | Supportive care, processes of care and management", +C10068,101138,The PRIEST Study: Pandemic Respiratory Infection Emergency System Triage,"Summary: The aim of this study is to find the most accurate triage method (the way of deciding the order of treatment of patients) for predicting severe illness among patients attending the emergency department with suspected respiratory infection (infection in the lungs) during a pandemic (when a disease has spread across many countries). The study will be observational and will not change patient care. Participating hospitals and ambulance trusts will use whatever triage method is most suitable for them, based on national and local guidance. The study will include all adults and children with suspected respiratory infection who attend the emergency department of a participating hospital, call 111 or 999 services or are dealt with by a 999 ambulance from a participating ambulance trust. Outcomes will be assessed based on the triage method used. Patients who die or require respiratory (lung), cardiovascular (heart and blood vessels) or renal (kidney) support will be considered as having an adverse outcome. In addition, if the pandemic leads to hospital resources being overwhelmed, meaning that patients with respiratory, cardiovascular or renal conditions are unable to access support, they will be considered to have had an adverse outcome. If patients survive to 30 days without requiring respiratory, cardiovascular or renal support they will be defined as having no adverse outcome. [COVID-19 amendment 23/03/2020] Description: We aim to optimise the triage of people using the emergency care system (111 and 99calls, ambulance conveyance, or hospital emergency department) with suspected respiratory infections during a pandemic and identify the most accurate triage method for predicting severe illness among patients attending the emergency department with suspected respiratory infection. Our specific objectives during the pandemic are: 1. To undertake continuous monitoring of the performance of the emergency care triage method (or methods) used for suspected respiratory infections during a pandemic 2. To identify clinical characteristics and routine tests associated with under-triage (false negative assessent) or over-triage (false positive assessment) during a pandemic 3. To determine the discriminant value of alternative triage methods for predicting severe illness in patients presenting with suspected respiratory infection during a pandemic 4. To inform policy makers and practitioners during a pandemic of the study's emerging findings. Our specific objectives after the pandemic are: 1. To determine the discriminant value of emergency department triage methods for predicting severe illness in patients presenting with suspected pandemic respiratory infection 2. To determine the discriminant value of presenting clinical characteristics and routine tests for identifying severe illness 3. To determine the independent predictive value of presenting clinical characteristics and routine tests for severe illness 4. To develop new triage methods based upon presenting clinical characteristics alone or presenting clinical characteristics, electrocardiogram (ECG), chest X-ray and routine blood test results, depending upon the data available and the predictive value of variables evaluated in objective 3",2021,-99,SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management", +C10069,294480,OCTAVE: Observational Cohort Trial -T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2,"Professor Pam Kearns, Director of the University of Birmingham's Cancer Research UK Clinical Trials Unit (CRCTU), which will be running the study, said: ""Current evidence shows that people with these medical conditions may not obtain optimal protection from established vaccines. ""Patients with significant underlying diseases were generally excluded from COVID-19 vaccine studies to date - it is now important to confirm that the COVID-19 vaccines work well in such conditions. ""We are pleased to be supporting this important nationally collaborative study that will inform the best use of the COVID-19 vaccines to protect these vulnerable patients."" The OCTAVE study will investigate the effectiveness of COVID-19 vaccines being used in the UK in 2021 in up to 5,000 people within these patient populations. Using a variety of state-of-the-art immune tests performed on blood samples taken before and/or after COVID-19 vaccination, researchers will determine patients' COVID-19 immune response and, therefore, the likelihood that vaccines will fully protect these groups from SARS-CoV-2 infection. Scientists do not yet know how long COVID-19 vaccines provide immunity for, and there may be an ongoing vaccination requirement against the disease for years to come. This may be especially so in people with weakened immune systems, due to drug treatments and underlying disease. Results from the OCTAVE study will help to inform how best to vaccinate patients with chronic conditions, and protect them from SAAR-CoV-2 infection. Professor Fiona Watt, Executive Chair of the Medical Research Council, which funded the study, said: ""This study is investigating the response to the new COVID-19 vaccines in people whose immune systems make them more vulnerable to COVID-19 and other infections. This will help ensure that those more at risk from infection receive the best protection possible.""",2021,-99,University of Birmingham,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase), +C10070,284229,Facilitating Accelerated CLinical evaluation Of Novel diagnostic tests for COVID-19 (FALCON C-19),"Summary: The aim of this study is to evaluate the accuracy of a number of commercially available tests for diagnosing COVID-19 infection within hospitals. Accurate diagnosis of infection, identification of immunity and monitoring the progress of the infection are of great importance to our response to COVID-19. Widespread population testing has proved difficult in western countries and has been limited by availability of tests, staff availability and long turnaround times (up to 72 hours). This has limited our ability to control the spread of infection and to develop effective ways to ensure early self- isolation of infected patients and early treatment for those most at risk. Industry has developed a number of new in vitro (outside the human body) diagnostic tests. To take advantage of the potential benefit of those tests we need effective assessment of the tests. This study will evaluate tests in three priority areas: - Evaluation of the accuracy of in vitro tests for the diagnosis of active infection with COVID-19; - Evaluation of tests to show the immune response to COVID-19; - Evaluation of tests for predicting the likely course of the disease in patients with suspected or confirmed COVID-19 infection. (This will not be done immediately but may start later). The study will take place in both primary healthcare (in the community) and secondary healthcare (generally hospitals) settings. The study described in this application (referred to as FALCON) focuses only on hospitals. A separate study (RAPTOR) will look at primary healthcare settings. Description: The United Kingdom and wider world is in the midst of the 2019 novel coronavirus (SARS-CoV-2) pandemic. Accurate diagnosis of infection, identification of immunity and monitoring the clinical progression of infection are of paramount importance to our response. Widespread population testing has proven difficult in western countries and has been limited by test availability, human resources and long turnaround times (up to 72 hours). This has limited our ability to control the spread of infection and to develop effective clinical pathways to enable early social isolation of infected patients and early treatment for those most at risk. The life sciences industry has responded to the pandemic by developing multiple new in vitro diagnostic tests (IVDs). To leverage the potential clinical benefit of those tests we require efficient but robust clinical evaluation. Therefore, to optimise resource utilisation in this global pandemic, we will conduct a platform adaptive diagnostic study on a national level, utilising a national network of expertise in the evaluation of diagnostic technology. CONDOR is the overarching platform which will be providing coordination, and as such, it has been deemed not to require submission to the HRA. Two research studies (FALCON and RAPTOR) which feed into this platform. This study will enable the evaluation of multiple assays in three priority areas: (1) Evaluation of the diagnostic accuracy of IVDs for active infection with SARS-CoV-2 (2) Evaluation of assays monitoring the immune response to SARS-CoV-2 infection (3) Evaluation of the prognostic value of commercially available tests for predicting prognosis in patients with suspected or confirmed SARS-CoV-2 infection. (This arm will not be active immediately but may be activated after initiation). Recognising the need for a holistic, specialty-agnostic approach, our overall programme of work will take place in both primary and secondary healthcare settings, spanning the breadth of a patient's journey. The study described in this application (referred to as FALCON) focuses only on secondary care settings. A separate study (RAPTOR) is being initiated to evaluate IVDs for COVID-19 diagnosis in community settings.",2021,-99,Manchester University NHS Foundation Trust,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10071,293182,"A phase II study of a candidate COVID-19 vaccine in children (COV006) A single-blind, randomised, phase II study to determine safety and, immunogenicity of the Coronavirus Disease (COVID-19) vaccine ChAdOx1 in UK healthy children and adolescents (aged 6-17)","Since emerging in Wuhan, China in December 2019, SARS CoV-2 has since rapidly spread to many other countries around the world, causing the disease known as COVID-19. Common symptoms of COVID-19 include fever, tiredness, and dry cough. Whilst about 80% of infected people have no or mild symptoms and will recover from the disease without needing special treatment, older people and those with underlying medical problems are more likely to develop serious illness. 1.7 millions deaths so far have been reported to the WHO. The World health Organisation declared the COVID-19 epidemic a Public Health Emergency of International Concern on 30th January 2020. Several vaccines have undergone development including ChAdOx1 nCoV-19, which has demonstrated an acceptable safety and efficacy profile in adults in phase 2/3 studies and has been approved for emergency use and routine deployment in the UK. Immunising children is likely to be an important step in gaining control of the pandemic in the UK, as teenagers have some of the highest swab positivity rates in the UK as of December 2020, and immunising school-age children is important to protect vulnerable adults e.g. teachers and carers. This study will give us valuable information on safety aspects of the vaccine and its ability to generate good immune responses against the virus in this age group. In total we will enrol 300 participants between the ages of 6 and 17 years of age.",2021,-99,N/A,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,Europe,,,,,United Kingdom,"Vaccines research, development and implementation",Phase 2 clinical trial, +C10072,287978,COVID-19 Germ Defence Implementation Primary Care implementation of Germ Defence: A digital behaviour change intervention to improve infection control during the COVID-19 pandemic,,2021,-99,University of Bristol,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,IPC in health care settings, +C10073,282608,"C-MORE Capturing MultiORgan Effects of COVID-19 Assessing the effects of Coronavirus Disease (COVID-19) on multiple organ systems and impact on quality of life, functional capacity and mental health","Summary: Although COVID-19 mostly affects the lungs, some people can develop damage to other organs. The symptoms of this disease can continue for months after the infection. The purpose of this study is to understand the effects of COVID-19 on the health of the lungs, heart, brain, liver and kidney and assess its effects on the quality of life, mental health and exercise capacity of affected individuals over a period of 12 months after the infection and compare these with those of people who have not had COVID-19. The researchers aim to study up to 616 patients who have been infected with COVID-19 and 62 people who have not been infected (control group) - and will use the control group as a benchmark to compare against the results of the infected group. Participants will be invited to attend up to 3 visits around three, six and twelve months after the infection. Controls who have not shown COVID-19 symptoms will attend only one visit. The visits will include magnetic resonance (MRI) (a system used in radiology to form pictures of the organs and the way they work) as well as assessments of breathing, exercise capacity and mental health. This research is organized by the Division of Cardiovascular Medicine at the University of Oxford and is funded by NIHR Oxford Biomedical Research Centre. Description: The purpose of this study is to understand the effects of COVID-19 on the health of the lungs, heart, brain, liver and kidney and assess its effects on the quality of life, mental health and exercise capacity of affected individuals over a period of 12 months after the infection and compare these with those of people who have not had COVID-19. We would like to study up to 616 patients who have been infected with SARS-CoV-2, (the virus that causes COVID-19) and 62 people who have not been infected. We will use the control group as a benchmark to compare against the results of the other group. Participants will be invited to attend up to 3 visits around three, six and twelve months after the infection. Controls who have not shown COVID-19 symptoms will attend only one visit. The visits will include magnetic resonance imaging of the lungs, heart, brain, liver and kidney as well as assessments of breathing, exercise capacity and mental health.",2021,-99,University of Oxford,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts, +C10074,279315,"COVAC 1: A first-in-human clinical trial in healthy young and elderly adults to assess the safety, immunogenicity and exploratory evaluation of efficacy of a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative","Summary: COVAC1 is a study that looks at a new vaccine against the virus (SARS-CoV-2) which causes COVID-19. There are two parts to the study. One part is to assess the safety of this vaccine, since this will be the first time that it has been used in humans. The second part is to see how well, and for how long, the vaccine activates the immune system. This trial is NOT looking at whether the vaccine is effective in terms of protecting people against infection. It is just working out how well the immune system responds. Safety will be looked at in 15 healthy young adults aged 18-45. They will be given one of three different doses (0.1, 0.3 and 1 µg) by injection into the muscle, going slowly from the lowest to the highest dose over a period of several weeks. They will be carefully checked for any reactions to the vaccine. As long as there are no safety problems, the second part of the study will start. About 100 participants aged 18-45 will be given one of three doses (0.1, 0.3 and 1 µg). Chance will determine which dose each person is given. The vaccine is given by injection into the muscle of the upper arm. Two injections, four weeks apart, are needed. Participants will be asked to record any symptoms in an online diary. In order to see how well the immune system is responding, they will give blood samples several times during the first 6 weeks; then monthly for a few months; then at 6 months and 12 months. As long as there are no serious adverse events after about 6 weeks a further 200 people or more, from multiple sites, will be assessed for safety using highest vaccine dose (1 µg). This part of the study will include people up to the age of 75. An independent committee will regularly review the information on safety and look at the immune responses to see which dose of the vaccine should be tested in future trials. Description: COVAC1 is a study that is looking at the use of a new vaccine against the virus (SARS-CoV-2) which causes COVID-19. There are two parts to the study. One part is to assess the safety of this vaccine, since this will be the first time that it has been used in humans. The second part is to see how well, and for how long, the vaccine activates the immune system. It is this activation that may provide protection against developing COVID-19. But this trial is NOT looking at whether or not the vaccine is effective in terms of protection. It is just assessing whether and how well the immune system responds. Since this is the first time the vaccine has been used in humans, the safety will be assessed initially in healthy young adults. 15 participants aged 18-45 will be given one of three different doses (0.1, 0.3 and 1 µg) by injection into the muscle, going slowly from the lowest to the highest over a period of several weeks. There will be careful monitoring for any reactions to the vaccine. As long as there are no safety concerns, the second part of the study can then be started. This will see how well the immune system has been activated using different dose levels of the vaccine. About 100 participants aged 18-45 will be given one of three doses (0.1, 0.3 and 1 µg). Chance will determine which dose each individual is given. The vaccine is given by injection into the muscle of the upper arm. Two injections, four weeks apart, are needed. There are likely to be mild side-effects near to the injection site. There may also be more general side-effects such as headache, temperature and chills. Participants will be asked to record any symptoms in an online diary. In order to see how well the immune system is responding, participants will need to give blood samples several times during the first 6 weeks; then monthly for a few months; then at 6 months and 12 months. This will happen at one study centre. In addition, as long as there are no serious adverse events after about 6 weeks of the second part of the trial, the safety evaluation will be expanded. A further 200 people or more, from multiple sites, will be recruited. The safety of the highest vaccine dose (1 µg) will be assessed. The age range will now also be extended to include people up to the age of 75. This is important, since we know older people are more at risk of serious complications from COVID-19, and so are most likely to benefit from a successful vaccine. An independent steering committee will regularly review the information on safety and look at the immune responses to see which dose of the candidate vaccine should go forward to effectiveness testing in future trials. Before this study can start, the protocol describing the procedures and information to be provided to volunteers will be reviewed by the national drug authority and a multi-centre research ethics committee.",2021,-99,Imperial College London,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Phase 1 clinical trial, +C10075,284320,RAPTOR C-19: RAPid community Testing fOR COVID-19 (RAPTOR C-19),"Summary: The aim of this study is to assess the diagnostic accuracy of a number of point-of-care tests (POCTS) for active COVID-19 infection in the community setting. The NHS urgently needs quick, accurate rapid diagnostic tests to diagnose people with COVID-19 or to confirm that people do not have the infection. POCTs can be used in community settings where there is no easy access to a specialist laboratory. They provide quick results that allow people to get immediate advice about self-isolation and treatment, potentially blocking further spread of infection in the community. Companies are quickly developing new rapid diagnostic tests, but we do not know how well they work. Some tests give a result like a pregnancy test by using a drop of blood from a finger prick. Others use saliva, or a swab to collect a sample from the nose or throat. Companies check that tests work in their laboratories, but usually tests do not work as well when used in the outside world with real patients. Accurate rapid diagnostic tests are important so that people are not falsely reassured when they are infected and are not wrongly diagnosed when they are not really infected. Our team manages a national monitoring system with a network of community settings including GP practices from all over England. These GP practices have been testing for COVID-19 since January 2020 with samples sent for laboratory tests. In this study, GP practices in the network will quickly compare new POCTs for COVID-19 with laboratory tests so we can see how good the new POCTs are in a coordinated and efficient way. Description: CONDOR is the overarching platform which will be providing coordination, and as such, it has been deemed not to require submission to the HRA. Two research studies (FALCON and RAPTOR) which feed into this platform.",2021,-99,University of Oxford,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10076,281904,"Investigating a Vaccine Against COVID-19 (COV002): A phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19","Summary: There are no currently licensed vaccines for COVID-19. This study will enable us to assess how well people of all ages can be protected from COVID-19 with this new vaccine called ChAdOx1 nCoV-19. It will also give us valuable information on safety aspects of the vaccine and its ability to generate good immune responses against COVID-19. The researchers will enrol small numbers of older adults (56-70 years, then 70+ years) before expanding to large numbers of adults across all ages (18+ years). After this we will also assess the vaccine in a small group of children (5-12 years). There will be between 9 and 14 visits over 12 months with a blood test at each visit. Participants will receive one or two doses of the new COVID-19 vaccine or a licensed vaccine which has been given routinely to teenagers in the UK since 2015 to protect against meningitis and sepsis. Some participants may be asked to complete an electronic diary for 7 days after each vaccine and update the diary if they have any illness for a month after vaccination. Description: This study will enableresearchers to assess how well people of all ages can be protected from COVID-19 with a new vaccine called ChAdOx1 nCoV-19. It will provide valuable information on safety aspects of the vaccine and its ability to generate good immune responses against the virus. The researchers will enrol small numbers of older adults (56-70 years, then 70+ years) before expanding to large numbers of adults across all ages (18+ years). After this we will also assess the vaccine in a small cohort of children (5-12 years).",2021,-99,University of Oxford,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial, +C10077,282655,"Pregnancy and Neonatal Outcomes in COVID-19: A global registry of women with suspected or confirmed SARS-CoV-2 infeciton in pregnancy and their neonates, understanding natural history to guide treatment and prevention","Summary: To better understand some specific research questions as to how COVID-19 affects early pregnancy, fetal growth, prematurity and virus transmission to the baby the researchers will construct a registry of women with suspected and confirmed COVID-19 from early pregnancy to after delivery of the baby. Healthcare professionals from the UK and across many international centres will contribute data via a web portal. Description: The current coronavirus outbreak (COVID-19) is likely to affect hundreds of pregnant women globally. Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratoy Syndrome (SARS), also coronaviruses, caused more severe illness - particularly lung infections- in pregnant vs. non-pregnant women. There has been a report of nine women affected by COVID-19 in the latter third of their pregnancy, many more are likely to be affected. There is a data-gap on the effect of SARs-CoV-2 infection and COVID-19 at other stages of pregnancy e.g. early pregnancy and its effect on the unborn and newborn baby. Maternity services and individual maternity centres are currently developing their responses using national and WHO guidance for non-pregnant women. PAN-COVID will develop a global database detailing a number of outcomes (death of the baby or mother, stillbirth, miscarriage, pregnancy complications, gestational age at delivery, delivery method and testing the baby for SARS-CoV-2). The aim of this database is to understand the natural history of SARS-CoV-2 and COVID-19 and the impact on mothers and their babies to guide both treatment and prevention.",2021,-99,Imperial College London,,Other,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis, +C10078,281259,"A phase I/II study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers","Summary: Researchers at University of Oxford are developing a coronavirus vaccine called ChAdOx1 nCoV-19. The vaccine acts by encouraging the immune system to recognise and attack the coronavirus. It is made from a harmless virus called an adenovirus that has been altered to produce the surface spike protein of COVID-19. The study will assess if healthy people can be protected from COVID-19 with this new vaccine. It will give information on the safety of the vaccine and how well it can create a good immune response against the virus. The first trials will be in younger adults, followed by people over 55 and, then larger trials in adults over 18 years, before studies in later school age children. In this trial over 1000 healthy adults, aged 18 - 55 years of age in the UK will be given either the coronavirus vaccine or a control vaccine (that cannot protect against COVID-19) on a random basis. Participants will be asked to complete a diary for 7 days after the vaccination to provide information on how they feel. They will be closely monitored by the study team. They will be asked to return for blood tests between 5 and 9 times over a 12-month period and information will be collected about any symptoms that occur after vaccination If the vaccine is shown to be safe and effective in these earlier trials, vaccine manufacturing will be increased to allow larger studies to take place. Description: A new virus causing respiratory disease emerged in Wuhan, China in December 2019 and has since rapidly spread to many other countries around the world, despite unprecedented containment efforts. The virus is part of the Coronavirus family which may cause respiratory infections ranging from the common cold to more severe diseases. This recently discovered coronavirus causes coronavirus disease COVID-19. The WHO declared the COVID-19 epidemic a Public Health Emergency of International Concern on 30th January 2020. There are no currently licensed vaccines or specific treatments for COVID-19. Vaccines are the most cost effective way of controlling outbreaks and the international community have stepped-up their efforts towards developing one against COVID-19. This study will enable us to assess if healthy people can be protected from COVID-19 with this new vaccine called ChAdOx1 nCoV-19. It will also give us valuable information on safety aspects of the vaccine and its ability to generate good immune responses against the virus. We will do this by randomly allocating participants to receive the vaccine or a placebo injection in addition to doing blood tests and collecting information about any symptoms that occur after vaccination. The study would enrol up to 510 healthy adults, aged 18 - 55 years of age living near to a study site in the UK. Dependent on the group, there will be between five and nine study visits over a 12 month period. Participants will be asked to complete a diary for 7 days after the vaccination and will be closely monitored by the study team.",2021,-99,University of Oxford,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial, +C10079,NIHR133443,PROphylactic TrEatment of COVID in Care Homes Trial (PROTECT),"The COVID-19 pandemic has had a devastating impact on care homes, causing illness and death and leading to restrictions on daily routines, including restricted visiting, that have impacted adversely on the health and wellbeing of residents and their relatives. Beyond public health measures to prevent infection (hygiene, masks, personal protective equipment, maintaining distance), we urgently need interventions to reduce the spread and severity of infection. Treatments, such as dexamethasone, may improve outcomes for care home residents who are sufficiently unwell. Vaccination against SARS-CoV-2 has commenced in care homes but its efficacy in older people with multiple comorbidities and immunosenescence is not yet established. It is likely that, even after vaccination, sporadic outbreaks of COVID-19 will continue to occur in care homes. We need to establish whether preventative treatments work in this setting to reduce either the transmission or severity of COVID-19. Such approaches should be complementary to vaccination and acute treatments. We will set up a large platform cluster-randomised trial that will test several treatments intended to reduce the spread of COVID-19 within care homes and/or reduce the risks of hospitalisation and death. We will study between one and three treatments at a time, which will be identified by the NIHR Prophylaxis Oversight Group. Treatments will be replaced in the study as they are shown to be either effective or ineffective. This process can, in principle, go on for many months or years. Care homes will be randomised to either active treatment or control. We will recruit approximately 12,000 residents from 400 care homes for older people (some of whom will include some younger people) from across the UK to allow three treatments to be compared with control/standard of care. We expect most of the interventions will be given for two months before their efficacy is tested. The ordinal primary outcome will be: all cause death, hospitalisation (or intent to hospitalise) for SARS-CoV-2 infection, asymptomatic or symptomatic infection in residents remaining in the care home, and no infection. Secondary outcomes will include the components of the primary outcome, referral for healthcare support, time to infection, cause-specific mortality, serious adverse reactions relevant to the intervention(s), cost effectiveness and process evaluation. We will also contribute to the development of a core outcome set for COVID-19 in social care settings. We will develop training materials including video and audio descriptions for care home staff and information sheets for residents to allow them to make an informed decision on whether to participate. These will be adapted for use by family members who will make decisions on behalf of residents who do not have mental capacity to provide consent. Patient Public and Carer involvement, including with Black and Minority Ethnic representation, will be embedded in the study through a hub (based with the trial team) and spoke (regional centres) model and will review all study materials and outputs. The trial will be run from the University of Nottingham with collaborators at the Universities of Cambridge, Edinburgh, Surrey and Warwick, and University College London. Our team of doctors, statisticians, trial methodologists, health economists, qualitative scientists and public partners are experienced in care home research. We will make the results of the trial rapidly available to ensure that COVID-19 guidelines are quickly updated and to prevent impact delay. This will include creating summaries for the general public, care home residents and their loved ones.",2021,2022,The University of Nottingham,2364877.44,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management | Prophylactic use of treatments | Therapeutics logistics and supply chains and distribution strategies",2021 +C10080,NIHR131847,Assessing the impact of COVID-19 on the physical activity of Year 6 children and their parents: Identifying scalable actions to mitigate adverse impacts & provide rapid evidence to policy makers,"Background: Physical activity is important for health and well-being in children and adults. The end of primary school is key for maximising physical activity into secondary school. Covid-19 and lockdown measures have had a profound impact on the whole system which surrounds and impacts on children and parents' physical activity. The closure of parks, schools, extra-curricular activities, as well as changes to employment, income, and housing security have all affected physical activity. These impacts are unlikely to be uniform with people living with greater inequalities are likely to be more profoundly affected. This project will examine the impact of COVID-19 on the physical activity of Year 6 children and their parents and what can be done to minimise adverse impacts of physical activity restrictions while not exacerbating inequalities. We will identify key knowledge so that if there is a second wave of the virus, we are better prepared to keep people active and can make decisions based on evidence of what works. Methods: The proposed study is a repeated cross-sectional quantitative design with linked qualitative study. The comparator will be pre-COVID data. For the quantitative data we will collect data at two time-points Time1 will be between March - December 2020. This will provide data on the acute impacts on physical activity. Time2 will assess the same measures, in the same schools a year later between January and July 2022 to provide information on chronic impacts. The primary outcome (for children and parents) will be accelerometer measured average minutes of moderate to vigorous intensity physical activity per day. We will also use child and parent surveys to assess the types and locations of physical activity, demographics, and psychosocial variables. We will use a school audit to assess physical activity policies and changes to provision since the virus. We will also examine the implications of COVID-19 on the time and resources that schools allocate to physical activity and family members health-related quality of life. Data will be compared to a survey of 1296 Year 6 children and their parents collected 3 years earlier, in the same schools using the same methods (Time 0). We will conduct focus groups with 48 children and interviews with 30 parents and 18 teachers in a sub-group of schools at Times 1 and 2 to identify how patterns of behaviour and provision have changed in response to the virus and what could be put in place to mitigate impacts. We will use multi-level models to examine differences in physical activity at Time 1, when contrasted with Time0. We will then examine the extent to which the family and school level variables explain differences. The process will be repeated for Time 2. The qualitative data will be analysed to identify identity changes in provision and actions that have been taken to mitigate impacts. We will conduct rapid analyses of the data at 5 time points to provide summaries of how physical activity patterns have changed and mitigation strategies that have some evidence of promise to policy makers. Timelines: This is a 27-month project starting March 2021. Anticipated impact: This study will provide data on the magnitude and type of changes in physical activity that have occurred in response to the pandemic but more importantly we will identify strategies that could be put in place at scale to mitigate adverse impacts.",2021,2023,"NHS Bristol, North Somerset and South Gloucestershire Clinical Commissioning Group",857488.14,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C10081,NIHR134283,A mixed methods rapid evaluation investigating the use of pulse oximetry in care homes across England to manage residents with COVID-19 and long-term health conditions,,2021,2021,University of Birmingham,,Unspecified,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C10082,NIHR133288,Interventions for the treatment of COVID-19: a network meta-analysis (Methodologically complex living systematic review with network meta-analysis),,2021,2022,Medical University of Vienna,13700,Other,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2021 +C10083,NIHR202481,Exploring older people's support needs for making healthier decisions about alcohol during COVID-19,"Research Question: How does promotion of healthier drinking amongst older people need to change during/after COVID-19? Background: One in three older people (aged 50+) has increased their alcohol intake during COVID-19, drinking at home in the context of stresses, boredom and loneliness. This is important for public health, as without intervention alcohol-related harm amongst older people will continue to increase, putting more pressure on health services. A good understanding is needed, of how older people s views and use of alcohol have changed during COVID-19, and their potential support needs to address hazardous alcohol use. Evidence will inform policymaking and service delivery, ensuring older people receive the right support to make healthy decisions about alcohol. Aim: To investigate how promotion of healthier drinking amongst older people needs to change during/after COVID-19. Objectives: 1. To understand how older people s views and use of alcohol have changed during COVID-19 2. To explore changes in older people s motivations to engage in healthy/unhealthy drinking during COVID-19 3. To explore older people s perceptions of the support they need to make healthier decisions about drinking during/after COVID-19 Methods: Qualitative study of older people s views and experiences relating to alcohol during COVID-19, with analysis of Drink Wise Age Well webchat records, where older people receive support for concerns about their drinking; and telephone interviews with a diverse national sample of higher-risk drinkers. Rapid evidence synthesis of research exploring how COVID-19 has affected older people s alcohol use and/or support needs. Timelines for Delivery: 6 months - with staged outcomes throughout. Anticipated Impact and Dissemination: This research will inform responses to older people s identified needs for support to make healthier decisions about alcohol, in alcohol and healthcare services. The applicant team is nested within the NIHR Policy Research Unit Older People and Frailty, and will utilise their existing relationships/regular meetings with policy customers (National Clinical Directors/Specialty Advisors, NHS England and NHS Improvement and local commissioning teams) to share emerging findings. We will also be supported by collaborators and alcohol harm prevention and treatment services Drink Wise Age Well, and Balance North East, to share findings with policy and practitioner audiences. The work will feature in webinars for policymakers and practitioners, briefings and academic publications.",2021,2021,Newcastle University,69652.17,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C10084,NIHR202259,The impact of Care Act Easements under the Coronavirus Act 2020 on co-resident older carers of partners with dementia,"The Coronavirus Act 2020 contains the unprecedented power for local authorities to suspend the majority of their duties within adult social care under the Care Act 2014, leaving only a residual duty to protect human rights (""easements""). This proposal investigates the impact of easements on co-resident older carers (age 70+) of partners living with dementia in the community. Such carers typically have their own high levels of health and care needs, but are often isolated and invisible. Eight local authorities triggered easements between April and August 2020. Many others have suspended services without triggering easements, potentially exposing themselves to legal action. In the event of local lockdowns or a second wave, easements are part of the strategic planning of a number of authorities. We currently have no understanding of the consequences of care easements for the people affected nor how to mitigate urgent needs arising from easements, from either carer or local authority perspectives. There is little official guidance that applies meaningfully to these carers. The objective of this project is to investigate the impacts of care easements on older co-resident carers of partners living with dementia to make recommendations about the operation of this legislation now and in the event of another wave or similar pandemic. The project aims to: document the impacts of care easements and reinstatement of statutory duties; compare these with experiences in local authorities where easements were not formally triggered but services may have been cut; understand how policymakers with safeguarding responsibilities have approached the issues; understand and document current urgent needs. We will work with our established networks and project partners, and specifically with a co-production group of 8 carers. There are three workstreams: 48 in-depth interviews with purposively selected carers in 4 local authorities, (a) two where easements were triggered for sustained time and (b) two where no easements were triggered. In-depth interviews with 10 safeguarding leads and 10 social work leads about services retrenchment and easements, exploring processes, ethical and legal frameworks, and burdens of decision making. A survey of our population of interest, seeking to obtain 500 responses; this will be an observational non-probability non-randomised sample validating reported experiences at scale and with sufficient power to compare groups in easement and non-easement local authorities. This will be multimodal utilising online and paper methods, using validated question sets asking about coping, support, socio-demographics, health and wellbeing, and questions developed from interview data. Understanding the impact of Care Act easements is crucial for government, local authorities, care providers, NHS commissioners and providers, civil society, charities, individuals and their families. This understanding is relevant for the drawing up and implementation of emergency legislation, drafting guidance, providing/resuming services, arguing for resources and system change, and protecting human rights. Specifically, evidence on this problem will inform the six-monthly parliamentary reviews of the Coronavirus Act, proposed Parliamentary debates, safety and regulation, access to health and social care, funding priorities, and systemic understanding of social care in the pandemic.",2021,2022,Contracting Organisation: The University of Manchester,278379.89,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Unspecified,Social Workers | Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C10085,NIHR202320,Appraising Social Distributions To Guide Levelling Up Health And Wellbeing During Covid-19 Recovery,"Research Question How can the costs and outcomes of COVID-19 and the policy response be appraised in a way that shows differences between population groups. The answer is contingent on the definition of relevant outcomes to inform policy. With improving health and wellbeing across society as a goal, evidence based policy relies on understanding the pathways by which COVID-19 and the COVID-19 policy responses affect these outcomes. In order for appraisal to reflect differences between social groups, it is vital to consider where direct impacts or pathways differ between population groups. Where inequality is identified, and where there are trade-offs between outcomes, evidence based policy relies on value judgements to reflect the degree of priority given to reducing inequality and improving outcomes. This scoping study will initiate a map for those undertaking economic evaluations related to COVID-19 that will support the inclusion of inequality impacts in appraisal. Background Existing health inequalities, the elimination of which is an objective in public funding, may have been exacerbated in avoidable ways by COVID-19 and the policy response to COVID-19. As unprecedented levels of public funds are shifted towards COVID-19 policy, further information on the costs and benefits of these activities is required to identify and prioritise those that offer value for money and provide proportionate benefits to disadvantaged groups. Our understanding of the disease and of how policy responses operate differently for different groups is developing over time. Health economic models of the impact of COVID-19 and associated policies must evolve with this to reflect how interventions are understood to effect changes in relevant costs and outcomes across population groups. Aims and objectives We will map current understanding of how COVID-19 and associated policies impact on health and wellbeing via direct impacts on health conditional on individual risk factors, and direct impacts on social determinants of health. We will scope out the level of evidence for differences in the direct impacts and the pathways from social determinants of health to final outcomes between population groups. Methods We will review economic evaluations of COVID-19 and similar pandemics. The results will summarise the social determinants of health captured, the outcomes included, the modelled pathways, the sources of evidence, the relative valuation of outcomes, and how differences between population groups was reflected. We will present the results to stakeholders, including members of the public, directors of public health and social services, experts in economic evaluation, public health and health inequality, and members of the Department of Health and Social Care and arms lengths bodies. Using the results of the review and consultation feedback we will construct an online resource for economic evaluation related to COVID-19. This will summarise the aspects of health and social determinants of health affected by COVID-19, indicating where evidence exists for unequal impacts and where evidence of inequality impact is lacking. Updatable searches and links to existing evidence sources will be provided.",2021,2021,University of York,79895.66,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Economic impacts | Health leadership and governance,2021 +C10086,NIHR134149,COVID19 Public Spaces Management,,2021,2022,University of Newcastle,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C10087,NIHR202326,"Rapid evaluation of the care home response to the need for palliative and end-of-life care during the COVID-19 pandemic: integration, communication and workforce resilience (CovPall_CareHome)","Background: COVID-19 has had a devastating impact on care homes, their residents and families, and staff. Over 20,000 care home residents in England have died from COVID-19 to date. Many more have experienced symptoms and distress. Palliative care is an essential component of the pandemic response. However, there has been limited examination of palliative and end-of-life care provision in English care homes during COVID-19, or strategies to improve this during subsequent pandemic peaks. Aim: To examine the response of care homes in England to meet the rapidly increasing need for palliative and end-of-life care for residents during the COVID-19 pandemic, and make recommendations for policy. Objectives: 1. To describe the response of care homes to palliative and end of life care needs during the COVID-19 pandemic, and the experiences, preparedness and impact on the workforce. 2. To explore in-depth the challenges and facilitators to providing palliative and end of life care in care homes during the pandemic. 3. To make recommendations for policy and develop guidance that helps to improve and sustain palliative and end of life care during current and future pandemic peaks. Methods: Rapid, multicentre observational study, comprising two Work Packages (WPs): WP1. On-line rapid survey, to map care home provision of palliative and end-of-life care. 400 care homes in England will be identified through established networks (Wave 1), augmented with purposive sampling to capture care homes with and without onsite nursing provision, geographical, socio-economic and ethnic diversity, and areas most affected by COVID-19 (Wave 2). Structured data and free text will include care home characteristics; confirmed/suspected COVID-19 positive residents; use of guidance on symptom control, end-of-life care, comprehensive assessment, Advance Care Planning, anticipatory prescribing, communication; service innovations during COVID-19; integration with healthcare services; workforce wellbeing, retention; preparedness to provide palliative and end-of-life care; and facilitators and challenges to palliative care provision. The primary outcome will be preparedness to provide palliative and end-of-life care. Regression models will examine the factors independently associated with the outcome. WP2. In-depth case studies to explore challenges and facilitators to providing palliative and end-of-life care for residents during the pandemic. 20-24 care homes, purposively selected from WP1 based on the findings. On-line or telephone qualitative interviews with care home managers/clinical leads will be conducted. WP1 data will inform the questions and analysis, using qualitative directed content analysis. Data triangulation will synthesise WP1 and WP2 findings, focusing on the challenges and facilitators to providing palliative and end-of-life care in care homes, and development of policies to improve and sustain this. Timelines: This 12-month project will deliver reports in months 4 and 10, and a stakeholder workshop in month 11. Impact and dissemination: The research is designed for short- and medium-term policy impact, through care home, Patient and Public Involvement (PPI), and policy collaboration. An interim analysis will inform short-term policy during winter 2020/2021. Reports will be accompanied by PPI summaries, evidence summaries and guidance for front-line staff. Academic papers will be published as preprints to ensure timely dissemination.",2021,2021,King's College London,249016.68,Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C10088,NIHR202482,Understanding the factors that shape care homes' responses to Government COVID-19 guidance on visiting arrangements,"Background While effective in limiting Covid-19 transmission, restrictions on family visits to care homes for older people can negatively impact residents emotional, cognitive and physical health and cause distress for families.1,2 Government has published guidance for care homes on establishing visiting policies that balance these risks, subject to local-area risk assessments from Public Health Directors.3 The guidance states, the first priority must remain preventing infections and visiting policy should still be restricted with alternatives sought wherever possible. However, it guides homes to develop a policy for limited visits which is made available and/or communicated to residents and families. This is challenging and potentially sensitive, with significant lobbying for increased access on compassionate and human rights grounds.4,5,6 Experience is evolving and care homes will manage these challenges differently.7,8,9,10 Research aims and objectives We will identify: range and diversity in care homes interpretation and implementation of guidance how scope for personalisation afforded by the guidance is reflected in policies need for, and use of, support (guidance, tools, assistance) to develop and implement policies perspectives on how policies are working; including feasibility, acceptability, equity and other impacts consultation with families and other stakeholders, including challenges, achievements and influence on policies how policies are communicated to residents, families and others; perspectives on how well this worked and why whether family members find policies understandable, fair and proportionate, and why how characteristics and circumstances of care homes, and contextual factors, influence all of the above The evidence generated by our study is intended to inform ongoing policy and practice during the current pandemic and be of relevance in the event of future epidemics and pandemics. Methods Stage one (months 1-6): To understand range and diversity and generate theory, we will administer a semi-structured questionnaire to care home managers or nominated senior staff (20 minutes; online or telephone) and review policy documents across 200 care homes, purposively-sampled. This provides sufficient breadth and depth and a sampling pool for later stages. Stage two (months 6-12): We will further develop explanatory analyses using twenty cases theoretically-sampled from the participating homes, involving 1-3 in-depth interviews with care home managers and nominated senior staff. Stage three (months 6-15): Thirty to thirty-five in-depth interviews with family carers, purposively-sampled to reflect diversity, will be conducted to explore understanding and views of care home policies. In all stages, data from will be thematically-analysed using NVivo; range and diversity will be fully described and patterns in the data identified and articulated.16,17,18 Findings will be refined and interpreted, and policy implications considered in consultation with our expert advisors and experts-by-experience. Supported by LSE and Care England s media and communications teams, we will monitor updates to Government guidance and key developments throughout to inform data-collection, analysis and interpretation. Three policy briefings and three peer-reviewed journal articles will be produced and promoted through our websites, professional networks, social media and public platforms. We will run joint webinars, give presentations and produce lay summaries.",2021,2022,London School of Economics and Political Science,275816.62,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C10089,NIHR202333,Social Care Recovery & Resilience: Learning lessons from international responses to the COVID-19 pandemic in long-term care systems,"Research question What can we learn from international evidence and experiences in order to support the recovery of the social care sector and to inform the development of policies to prevent and manage future outbreaks in social care settings in England? Background The first wave of Covid-19 has had an enormous impact on people who use and provide long-term care in England, with substantial excess mortality, compared to previous years, both for people who use home care and who live in care homes, and other impacts on mental and physical health, it has also had a major impact financial impact on care providers. As England faces a second wave and considers the recovery of the sector, there is an opportunity to learn more in-depth from relevant experiences of other countries in implementing measures to prevent and mitigate these impacts in care settings and through taking a systematic and rigorous approach to synthesizing emerging scientific evidence about which measures have worked well or not. Aims and objectives We aim to facilitate learning from the scientific evidence and relevant experiences of other countries in preventing and mitigating Covid, as well as recovering from its impacts in social care setting through: Co-development of a framework to provide strategic direction for how the social care sector in England can recover from, and respond to, Covid-19 (we define the social care sector as care provided in residential and community settings, by paid and unpaid carers) Synthesis of international evidence and lessons learnt that are relevant to the English social care sector Informing the development of policies and practices to support recovery and better prevent and manage future outbreaks Methods We will use situational analysis and Theory of Change (ToC) to establish a framework from which to assess the relevance of international experiences and evidence to the social care system in England. We will then carry out scoping reviews to map and synthesise empirical evidence on measures that can support the social care sector in preventing and mitigating the negative impact of Covid. We will then use a case study approach, including document analysis and interviews, to review in detail the experiences and learnings from 4 countries. Finally, we will apply the framework developed through ToC to synthesise findings from these work streams. Timelines for delivery The project plans to start on the 1st of November and will last for 18 months. The work plan has been organized to deliver outputs in a timely manner as practicable, recognising the critical nature of the Covid pandemic. Anticipated impact and dissemination The project s framework and priorities will be co-developed with stakeholders, to ensure that the research is relevant and useful within an English social care context. The team is well positioned to ensure effective and timely dissemination through their own policy and practice networks, their institutions, relationships with media and the dissemination platforms provided by their respective institutions and the LTCcovid.org website.",2021,2022,London School of Economics and Political Science,640057.15,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +C10090,NIHR134153,Evaluating the adaptation of delivery of the National Exercise Referral Scheme (NERS) to a virtual platform as a result of COVID-19,"Aim To examine the impact of using face-to-face or remote modes of delivery for NERS in order to support future decision making about programme implementation. Research questions 1 What is the effect on service user uptake of offering either the face-to-face or remote programme? 2 What is the effect on service user engagement of delivering either face-to-face or remote exercise sessions? 3 What is the effect on service user retention of delivering either the face-to-face or remote programme (from 4+ weeks)? 4 What are the facilitators and barriers to uptake, engagement and retention for the standard and remote programme? 5 What is the effect on health and wellbeing outcomes of delivering either the face-to-face or remote programme (from 4+ weeks)? 6 What do exercise referral professionals perceive as the facilitators and barriers to delivering the standard and remote programme? 7 Do exercise referral professionals perceive that mode of delivery influences their ability to deliver the programme? 8 What are the expected resources and corresponding costs of delivering core parts of the programme, and do they differ for face-to-face and remote delivery? Study design overview This is a mixed methods study. Research questions will be answered using existing, routinely collected monitoring and evaluation data collected by the NERS programme, and additional qualitative data. The work will be organised across four workstreams as follows: Workstream 1: Qualitative process evaluation with service providers Workstream 2: Qualitative process evaluation with service users Workstream 3: Quantitative outcome and health economic analysis Workstream 4: Data synthesis and dissemination",2021,2022,University of Hertfordshire,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C10091,NIHR202293,The other keyworkers in care homes: implications of including domestic staff in social care workforce strategies and practices relating to Covid-19 recovery,"Ancillary or domestic workers in care homes are key to infection control, routine cleaning and housekeeping tasks; they engage with residents; and assist care workers providing personal care. In general, information available depicts the ancillary workforce as: low paid, but facing high risks; comprising many shielded workers, unsure about coming to work; once at work, uncertain about their safety; and worried about residents and their own families contracting Covid-19. The picture, however, lacks clarity, with ancillary workers presented as both much loved by residents, but also possible sources of contagion. These competing views encourage the development of evidence-based policy-making and workforce strategies. This 10-month study addresses the following research questions over 2 phases: How have ancillary workers experienced the pandemic, in particular its impact on their work role, personal safety and mental health, organisational commitment, and workplace support? How have work practices been changing during the pandemic from the perspective of ancillary workers, their managers, HR managers, residents and staff? Has the treatment of ancillary workers been perceived to impact care quality in homes according to multiple perspectives? How can policy and practice be developed to ensure ancillary workers are better prepared, supported and equipped to deal with future waves of Covid-19 and beyond as services are reopened and reset? How did demographic features of the ancillary workforce - BAME background, migrant, socio-economic status - impact on work-related experiences of the pandemic, with implications for staff safety and wellbeing? What does documentary analysis of care homes policies and other sources, for example Care Quality Commission (CQC) reports, tell us about support of ancillary staff? What international evidence is available about practices of supporting ancillary staff in care homes? What would be are the elements of a co-produced good practice model for managing and supporting ancillary staff in care homes in the Covid-19 context? Phase 1 will include interviews with: 50 ancillary staff; 15-20 care home and Human Resource managers; 8-10 residents and relatives. We will examine care home documents: inspectors reports, staff handbooks, job descriptions, to develop a comprehensive picture of the work context. Drawing upon our networks, we will interview people in different types of care homes, and with different personal/employment characteristics, to examine how management practice reflects variety of ancillary staff and activity in the Covid-19 context. In Phase 2, we will use findings from Phase 1 to co-produce a good practice model for employing and supporting ancillary or housekeeping staff in care homes relevant to policy making in Covid-19 and social care. We will get feedback from stakeholders and finalise a consensus model that increases support for these staff in recovery or reorientation of care home services. Study outputs will include: a detailed report on experiences and treatment of ancillary staff during the pandemic from different stakeholder perspectives; and a coproduced good practice model for policymakers and for care home providers. We will publicise our resources to managers responsible for HR, care home managers, wider care home sector; and produce policy options for national social care policymakers.",2021,2021,King's College London,229053.04,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers | Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C10092,NIHR202322,Understanding the disruption of children and young people's health and healthcare use during and after COVID-19 to inform healthcare and policy responses,"Research Questions 1. What are the differences between expected and observed NHS activity for children and young people (CYP; 0-24 years) during the first COVID-19 pandemic wave and over the next year, and how does this vary by setting, diagnostic category and patient characteristics 2. For which patient groups is the pandemic period linked with adverse outcomes Background CYP health and wellbeing have been markedly affected by the response to the COVID-19 pandemic despite experiencing few direct effects from infection with SARS-CoV-2. Children s services were markedly disrupted during the pandemic and these disruptions continue, resulting in a mix of health harms and benefits for CYP that are poorly understood. Aims Short-term: To inform planning for winter and future pandemic waves; to use health service use data as a proxy for health outcomes and understand the mix of harms and benefits arising from reduced activity during the first wave Medium term: To use insights from analysis of COVID impact and new metrics to inform healthcare policy, in particular the development of integrated care systems and population health management at STP/ICS level (ie to build back better ). Methods: Mixed-methods: Participatory work with CYP and professionals together with secondary analyses of administrative healthcare datasets. Workpackage (WP) 1: Patient/public involvement and expert consultation work Focus groups and online consultation work with CYP and consultation/consensus exercises with RCPCH subspeciality groups and other relevant stakeholders, including charities. WP2: Analysis of trends in primary care and hospital activity Datasets: Secondary Users Survey (SUS), Hospital Episode Statistics (HES), Clinical Practice Research Database (CPRD), ONS Mortality data, RCGP dataset We will: Calculate ratios of observed:expected NHS activity for CYP (0-24 years) during the initial Covid-19 period and subsequently. Expected (denominator) rates will be modelled using 5 years historical data, thus accounting for seasonal variation, secular activity trends and coding changes over time. Separate analyses will be performed by setting, diagnostic category and patient characteristics (including age, sex, deprivation, ethnicity, geographical location) Estimate impact of reduced activity on health outcomes Estimate cumulative unmet need for care WP3: Analysis of new linked datasets. We will explore wider Covid-19 impact through new data linkages, with a range of planned linked datasets accessed through NHS England and PHE. Timelines for Delivery The project will run for 18 months from November 2020 (Month 1) to May 2022 (M18). WP1 will run M1 to 18 WP2 will run M1 to 12 WP3 will run M6 to 18 Anticipated Impact and Dissemination As a partnership between two universities and three key national bodies, this project will have rapid and meaningful impact on major policy decisions, as well as influencing local service planning across the country. We will disseminate findings through PPI partners, academic publications and directly to policymakers, particularly NHS England and regions.",2021,2022,"University College London, Great Ormond Street Hospital",555692.64,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health leadership and governance,2020 +C10093,NIHR202851,Covid-19 heterologous prime/boost vaccine study,"The COVID-19 pandemic has stimulated the development of a large number of potential COVID-19 vaccines (1, 2) and it is likely that at least two of these will be licensed and available during 2020/2021. Most vaccines in development are expected to be licensed as a two dose, homologous prime/boost schedule. Given the anticipated programmatic challenges of immunising large proportions of the population, there would be advantages to having flexible immunisation programmes where the second dose is not necessarily the same as the first dose, i.e. a permissive approach to using heterologous prime/boost schedules. Accordingly this study will determine the reactogenicity and immunogenicity of heterologous prime/boost schedules for candidate COVID-19 vaccines that are potentially to be deployed in the UK. The vaccines to be studied in this protocol will primarily be determined by those made available to the Department of Health and Social Care (DHSC) for population use. This will be an adaptive platform study, so as further vaccines get their licensure in the UK, they can be added to the trial, increasing the number of prime-boost vaccine permutations. The population to be studied will be adults over the age of 50 years; including those with comorbidities classified as mild/moderate/well controlled, as immunisation will most likely be prioritised for an older adult population with co-morbidities.Recruitment of individuals identifying as being of black and minority ethnicity will be prioritised. The sample size will be 460 participants, consisting of 4 group of 115. Vaccines will be given at 28 day intervals. All participants will have bloods tests at day 0, 28, 56, 112 and 365, and participants in the immunology sub-group (N=100, 25 per group) will have additional blood samples taken at day 7, 14, 35 and 42. The primary endpoint will be anti-SARS-CoV2 spike IgG at day 56 (1 month after the booster dose). This is a non-inferiority study, with the non-inferiority margin being a 0.63 fold-difference between the anti-SARS-CoV2 spike IgG geometric mean concentration in the heterologous boost arm and that in the homologous boost arm. The standard deviation of GMC on log scale (base 10) is 0.4 based on the current available data (1). Allowing for 25% of participants withdrawing or being sero-positive at baseline the sample size of 460 achieves 90% of power at one-sided 1% significance level.",2021,2022,University of Oxford,5106116.7,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Clinical trial (unspecified trial phase)",2020 +C10094,COVID-19-Risk Prediction Tool,COVID-19-Risk Prediction Tool,,2021,2022,University of Oxford,1606666.25,Other,Not applicable,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C10095,COVID-19-RECPLAS,The use of convalescent plasma to treat hospitalised and critically ill patients with COVID-19 disease,,2021,2021,University of Oxford,3909898.75,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management",2020 +C10096,PR-ST-0405-10001,Systematic Review of the Association of Coronavirus with Population Density and Climate,,2021,2020,Nottingham University Hospitals NHS Trust,6820,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility,2020 +C10097,COVID-19-AHL01,COVID19 IgG Lateral Flow Test,,2021,2020,Abingdon Health Ltd,3100000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C10098,CO-CIN-01,Clinical Characterisation of COVID-19 admitted to hospitals in the United Kingdom,,2021,2021,University of Liverpool,8283200,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C10099,COVID-19-RSC,"RECOVERY-RS Respiratory Support: Respiratory Strategies in COVID-19; CPAP, High-flow, and standard care",,2021,2021,University of Warwick,1930004.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase)",2020 +C10272,101015990,RESpondIng to outbreaks through co-creaTIve sustainable inclusive equality stRatEgies,"The aim of RESISTIRE is to: 1) understand the impact of COVID-19 policy responses on behavioural, social and economic inequalities in the EU27, Serbia, Turkey and the UK on the basis of a conceptual gender+ framework, and 2) design, devise and pilot policy solutions and social innovations to be deployed by policymakers, stakeholders and actors in different policy domains. RESISTIRE proposes a three-cycle approach, combining quantitative and qualitative research with co-creation. The process is repeated every 6 months, each cycle producing operational results and integrating insights from the previous one. Each cycle involves: • Extensive mapping of policy and societal responses to COVID-19, secondary survey data, workshops with civil society, interviews with public authorities, and individual narratives collected from precarious and vulnerable groups, and translated into operational insights • Development of adequate responses and operational tools from a holistic perspective, with a co-design approach involving multiple stakeholders, with recommendations for actions for policymakers, stakeholders and actors in the field. • Launch of pilot actions to demonstrate the potential impact of a range of proposed solutions. • Dissemination of knowledge, development of policy recommendations and empowerment of stakeholders to exploit project results. RESISTIRE relies on a strong multi-disciplinary consortium of ten European research, innovation, and design partners, with a well-established network of healthcare stakeholders. It is designed to achieve its results through multi-disciplinary research insights, cross-sectoral co-creation, solution development and a wide dissemination strategy. The project will provide in-depth knowledge and understanding of existing problems, as well as current and future priorities and solutions. As a result, it will contribute to the reduction of inequalities arising from COVID-19 policy and how to redress them.",2021,-99,European Science Foundation,6328575.5,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,Gender,,,France,Austria | Belgium | Bulgaria | Croatia | Cyprus | Czech Republic | Denmark | Estonia | Finland | France | Germany | Greece | Hungary | Ireland | Italy | Latvia | Lithuania | Luxembourg | Malta | Netherlands | Poland | Portugal | Romania | Slovakia | Slovenia | Spain | Sweden | Serbia | Turkey | United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C10294,unknown,An international randomised trial of additional treatments for COVID-19 in hospitalised patients who are all receiving the local standard of care,,2020,-99,Indian Council of Medical Research (ICMR),404000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | WHO,India | International,International | South-East Asia,South-East Asia,Unspecified,,,,India,,Clinical characterisation and management,Clinical trials for disease management, +C10295,unknown,Human monoclonals to COVID-19,,2020,-99,"International Centre for Genetic Engineering and Biotechnology, New Delhi",105600,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Emory Vaccine Center | Indian Council of Medical Research (ICMR),India | United States of America,Americas | South-East Asia,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",, +C10296,unknown,"Outcomes of elective cancer surgery during the COVID-19 pandemic crisis: an international, multicentre, observational cohort study (CovidSurg-Cancer)",,2020,-99,Christian Medical College,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Birmingham,India | United Kingdom,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10297,unknown,"COVID-IHPBA: A snapshot study on the outcomes of hepatobiliary and pancreatic surgery during the COVID-19 pandemic: an international, multicentre, observational cohort study",,2020,-99,Tata Memorial Hospital,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | International Hepato-Pancreato-Biliary Association (IHPBA) (USA),India | United States of America,Americas | South-East Asia,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10298,unknown,"Use of novel in-vitro diagnostic technologies (NAOR platform, Terasystem Breath Analyzer, VIRION test and Voice Pattern test) and RT-PCR for rapid testing of SARS-CoV-2 in Indian population",,2020,-99,Defense Institute of Physiology & Allied Science (DIPAS),,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,DDR&D (Israel) | DRDO (India) | Indian Council of Medical Research (ICMR),India | Israel,Eastern Mediterranean | South-East Asia,South-East Asia,South-East Asia,,,,India,India,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10299,unknown,Establishing sentinel sero-surveillance to monitor the trend of SARS-nCoV-2 infection transmission in the general population in rural Western India,,2020,-99,KEM Hospital Research Centre,82907,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Indian Council of Medical Research (ICMR),India | United Kingdom,Europe | South-East Asia,South-East Asia,South-East Asia,,,,India,India,Epidemiological studies,Disease transmission dynamics, +C10300,unknown,COVID-19 Pandemic and its impact on dental students,,2020,-99,DY Patil Dental School,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | The University of Iowa,India | United States of America,Americas | South-East Asia,South-East Asia,Americas,,,,India,United States of America,"Secondary impacts of disease, response & control measures",Social impacts, +C10301,unknown,Assessing the tobacco consumption patterns and willingness to quit among tobacco users during COVID-19 lockdown in India,,2020,-99,Health Related Information Dissemination Amongst Youth,7563.46,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Edinburgh,India | United Kingdom,Europe | South-East Asia,South-East Asia,South-East Asia,,,,India,India,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C10302,unknown,World Heart Federation COVID-19 and Cardiovascular disease (CVD) survey,,2020,-99,Public Health Foundation of India,105284.62,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | World Heart Federation (WHF),India | Switzerland,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,Clinical characterisation and management,Disease pathogenesis, +C10303,unknown,European Society of Intensive Care Medicine Covid-19 Project (UNITE-COVID),,2020,-99,Tata Memorial Centre,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Society of Intensive Care Medicine | Indian Council of Medical Research (ICMR),Belgium | India,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management", +C10304,unknown,Perceptions about Ethics of Public Health Behavioral Interventions during the Covid 19 Outbreak,,2020,-99,Seth G S Medical College and KEM Hospital,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | The Forum for Ethical Review Committees in the Asian and Western Pacific Region (FERCAP),India,South-East Asia | Western Pacific,South-East Asia,Unspecified,,,,India,,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C10305,unknown,Prospective validation of a probability calculation for venous thrombosis in patients with COVID-19 infection,,2020,-99,Christian Medical College,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Indiana,India | United States of America,Americas | South-East Asia,South-East Asia,Unspecified,,,,India,,Clinical characterisation and management,"Supportive care, processes of care and management", +C10306,unknown,"Evaluating the Impact of COVID-19 and Youth-Focused COVID-19 related Public Health Messaging in New Delhi, India",,2020,-99,Lady Hardinge Medical College,3774.75,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | National Institutes of Health (NIH),India | United States of America,Americas | South-East Asia,South-East Asia,Africa | South-East Asia,,,,India,India | Uganda,"Policies for public health, disease control & community resilience",Communication, +C10307,unknown,COVID-19 prevalence during pregnancy and pregnancy outcomes in 8 low and middle-income sites: A Global Network Study,,2020,-99,J. N. Medical College,44800,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | National Institutes of Health (NIH),India | United States of America,Americas | South-East Asia,South-East Asia,Unspecified,,,,India,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Prognostic factors for disease severity, +C10308,unknown,Continuous Monitoring of Pooled International Trials of Convalescent Plasma for COVID-19 Hospitalized Patients COMPILE,,2020,-99,ICMR,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | NYU Grossman school of Medicine,India | United States of America,Americas | South-East Asia,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Clinical trials for disease management, +C10309,unknown,GlobalSurg-CovidSurg Week: Determining The Optimal Timing For Surgery Following SARS-CoV-2 Infection,,2020,-99,Christian Medical College,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Birmingham,India | United Kingdom,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts", +C10310,unknown,The Vascular Surgery COVID-19 Collaborative (VASCC),,2020,-99,Christian Medical College,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Colorado,India | United States of America,Americas | South-East Asia,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management", +C10311,unknown,Trends in COVID19 epidemic and Community Impact study,,2020,-99,Christian Medical College,60456.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Edinburgh,India | United Kingdom,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,Epidemiological studies,Disease transmission dynamics, +C10312,unknown,The impact of the COVID-19 lockdown period on emergency surgery for traumatic brain and spinal injuries: a multicentric international study,,2020,-99,National Institute of Mental Health and Neuro Sciences (NIMHANS),,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Modena and Reggio Emilia,India | Italy,Europe | South-East Asia,Europe,Europe,,,,Italy,Italy,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10313,unknown,"A phase 2/3, observer-blind, randomized, controlled Study to determine the safety and immunogenicity of Covishield (covid-19 vaccine) in healthy Indian adults",,2020,-99,ICMR-National Institute for Research in Tuberculosis (NIRT),100000,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | University of Oxford,India | United Kingdom,Europe | South-East Asia,South-East Asia,South-East Asia,,,,India,India,"Vaccines research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial, +C10314,unknown,Risk of COVID-19 re-infection and its predictors,,2021,-99,Christian Medical College,837315.5,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation | Indian Council of Medical Research (ICMR),India | United States of America,Americas | South-East Asia,South-East Asia,Unspecified,,,,India,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C10315,unknown,Establishment of an Indo-U.S. Molecular Biomarker Knowledge Network for COVID-19,,2021,-99,Amrita Institute of Medical Sciences and Research Centre,25400,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | Indo-US Science and Technology Forum,India,South-East Asia,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",, +C10316,unknown,An International audit of Heparins in Practice - COVID-19 infection (HIP-CoV),,2021,-99,P D Hinduja National Hospital & Medical Research Centre,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | Liverpool School of Tropical Medicine,India | United Kingdom,Europe | South-East Asia,South-East Asia,Unspecified,,,,India,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management", +C10317,unknown,Evaluating SARS-CoV-2 Burden in Urban and Rural Communities in India and Uganda: a Seroprevalence and Wastewater-based Epidemiological Study,,2021,-99,Dr. G.M Taori Central India Institute of Medical Sciences,240674.82,Viruses | Environment,Not applicable,Not Applicable,Rural Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Indian Council of Medical Research (ICMR) | UK Research and Innovation (UKRI),India | United Kingdom,Europe | South-East Asia,South-East Asia,Africa | South-East Asia,,,,India,India | Uganda,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics | Disease surveillance & mapping, +C10318,unknown,Risk of transmission of COVID-19 by a confirmed index case among contacts living in same households- A study in India,,2021,-99,Amrita Institute of Medical Sciences,90410,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | WHO,India | International,International | South-East Asia,South-East Asia,South-East Asia,,,,India,India,Epidemiological studies,Disease transmission dynamics, +C10319,unknown,"COVID-19 epidemiological sub studies under the ongoing study ""Strengthening evidence based advocacy for influenza prevention and control in India""",,2021,-99,All India Institute of Medical Sciences,527550,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CDC | Indian Council of Medical Research (ICMR),India | United States of America,Americas | South-East Asia,South-East Asia,South-East Asia,,,,India,India,Epidemiological studies,Impact/ effectiveness of control measures, +C10320,unknown,A pilot study of the effects of helminth infection and SARS CoV 2 seropositivity on immune response and the intestinal microbiota in India,,2021,-99,ICMR-National Institute for Research in Tuberculosis (ICMR-NIRT),60000,Unspecified,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | National Institutes of Health (NIH),India | United States of America,Americas | South-East Asia,South-East Asia,South-East Asia,,,,India,India,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10321,unknown,"An International Multicenter, Adaptive, Randomized Double-Blind, PlaceboControlled Trial of the Safety, Tolerability and Efficacy of AntiCoronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19",,2021,-99,Indian Council of Medical Research (ICMR),564912,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | National Institutes of Health (NIH),India | United States of America,Americas | South-East Asia,South-East Asia,South-East Asia,,,,India,India,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C10322,unknown,"A Phase 2/3, Observer-blind, Randomized, Controlled Study to Determine the Safety and Immunogenicity of Covovax [Sars-cov-2 Recombinant Spike Protein Nanoparticle Vaccine (Sars-cov-2 Rs) With Matrix-m1™ Adjuvant] in IndianAdults",,2021,-99,ICMR-National AIDS Research Institute (ICMR-NARI),996127.4,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,360biolabs | Indian Council of Medical Research (ICMR) | Novavax,Australia | India | United States of America,Americas | South-East Asia | Western Pacific,South-East Asia,South-East Asia,,,,India,India,"Vaccines research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial, +C10323,unknown,International study of COVID-19 Antibody Response under Sustained immune suppression in Inflammatory Bowel Disease (IBD),,2021,-99,All India Institute of Medical Sciences(AIIMS),24931.11,Unspecified,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | The Leona M. and Harry B. Helmsley Charitable Trust,India | United States of America,Americas | South-East Asia,South-East Asia,Unspecified,,,,India,,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10325,unknown,Risk factors for SARS-CoV-2 infection among health care workers in India: A Case Control Study,,2021,-99,Amrita Institute of Medical Sciences and Research Centre,66550,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Indian Council of Medical Research (ICMR) | WHO,India | International,International | South-East Asia,South-East Asia,South-East Asia,,,,India,India,Epidemiological studies,Disease susceptibility, +C10326,COVID-2020-12371735,The double-edged role of innate immunity in SARS- CoV-2 infection: Dissecting new potential therapeutic targets,,2020,-99,NEUROMED,662349.98,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies, +C10327,COVID-2020- 12371640,Innate and adaptive immunity in COVID-19: from mechanisms to patients,,2020,-99,HUMANITAS,916552.68,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10328,COVID-2020- 12371760,Baseline Immunity status effect on sArs-cov2 presentation and evolution: comparison between immunocompetent and immunocompromised patientS (BIAS study),,2020,-99,SAN MATTEO,619632,Unspecified,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10329,COVID-2020- 12371817,"Exploiting immunopathogenic mechanisms for establishing predictive markers, diagnostic tools and medical countermeasures in COVID-19",,2020,-99,SPALLANZANI,988445.51,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity, +C10330,COVID-2020- 12371781,Deconstructing host-virus interactions to identify biomarkers and therapeutic targets for COVID-19,,2020,-99,MAGGIORE MILANO,923478.78,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C10331,COVID-2020- 12371808,"Endothelial, neuthrophil, and complement perturbation linked to acute and chronic damage in COVID-19 pneumonitis coupled with machine learning approaches",,2020,-99,IST.TECN.AVANZ Reggio Emilia,864087.54,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,Digital Health,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10332,COVID-2020- 12371617,Clinical and biological characterization of patients with COVID-19,,2020,-99,SAN RAFFAELE MILANO,836902.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,Clinical characterisation and management,Disease pathogenesis, +C10333,COVID-2020- 12371675,"COVID19: epidemiological, clinical, genetic, and social determinants of infection and disease progression",,2020,-99,SPALLANZANI,667871.1,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis, +C10334,COVID-2020- 12371849,Host-pathogen interaction and immune response to SARS-CoV-2: molecular mechanisms and their therapeutic exploitation,,2020,-99,HUMANITAS,820741.76,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity", +C10335,COVID-2020- 12371619,COVIDIAGNOSTIX - Health Technology Assessment in Covid serological diagnostics,,2020,-99,GALEAZZI,889938.02,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Ministry of Health - Italy,Italy,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10366,173065,"Evaluation Of Innovative Risk Mitigation Services In The Context Of Dual Crises Of COVID-19 And Overdose Among People Who Use Opioids In Vancouver, BC","Through funding from the Canadian Institute of Health Research (CIHR) and MSFHR, Principal Investigators Dr. Kanna Hayashi, Research Scientist at the BC Centre on Substance Use (BCCSU) and St. Paul's Hospital Chair in Substance Use Research and Assistant professor in the Faculty of Health Science at Simon Fraser University (SFU) along with Dr. Kora DeBeck, Research Scientist at the BCCSU and Associate Professor in the SFU School of Public Policy aim to conduct preliminary evaluation of two novel measures introduced by the BC government in March 2020 to address the dual crisis of overdose and COVID-19. Specifically, these measures include expanding the opioid agonist treatment (OAT) prescription guidelines and pandemic prescribing of pharmaceuticals (e.g. opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these interventions have not been evaluated. The proposed BC-based research aims to fill critical knowledge gaps by examining the reach and preliminary impacts of pandemic prescribing and expanded OAT prescription services among people who use opioids in urban Vancouver. Through this work, the research team, which consists of highly productive investigators and knowledge users with direct clinical and policy expertise, seeks to inform efforts to improve the delivery and effectiveness of the interventions.",2021,-99,Simon Fraser University,,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Michael Smith Foundation for Health Research,Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery, +C10367,173116,Tracking The Prevalence And Incidence Of Modifiable Suicide Risk Factors During The COVID-19 Pandemic To Inform Targeted Suicide Prevention In British Columbia,"Problem: Half of Canadians report worsened mental health since the COVID-19 pandemic began disrupting our lives this Spring. These impacts, combined with rising prevalence of known suicide risk factors such as unemployment and financial hardship, social isolation, alcohol and substance use, relationship strain and domestic violence, have raised concerns that of rising suicide risk in the Canadian population. Canada loses 3,800 to 4,500 lives to suicide each year. Suicide death and bereavement confer long-term psychological and social risk to families and communities. A small increase in suicide rate can thus result not only in excess loss of life, above and beyond the direct impacts of the pandemic, but also confer long-term vulnerability in our communities. Research: In collaboration with an international team of researchers led by investigators Shanaya Rathod and Peter Phiri in the UK, our Canadian team aims to characterize the specific mental health and related cognitive impacts of the COVID-19 pandemic to inform evidence-based policy that can mitigate secondary mental health and suicide risk. We will conduct three pan-Canadian general population surveys, in September 2020, December 2020, and March 2021. For each survey, we will recruit at least 5,000 community adults, balanced by sex, age, and geographic region. Surveys will focus on Canadians' emotional, physical, and cognitive wellbeing across distinct phases of the pandemic. In addition, we will work with mental health service leaders, providers and users to co-create supplemental surveys to assess the mental health experiences and needs of three potentially vulnerable groups: frontline health workers, Indigenous peoples, and people living in rural or remote areas. Our results can inform mental health strategies by identifying where, with whom, and what kind of intervention is needed to effectively reduce suicide risk in the population. Support from MSFHR and the BC Ministry of Health will enable us to over-sample British Columbians so that we can understand mental health needs within this province and identify sectors or populations with mental health needs. Research Team: Our interdisciplinary research team, led by Co-PIs Brianna Turner, Theone Paterson, and Chris Lalonde, includes psychology, social work, and sociology researchers, as well as community knowledge users representing the United Way of the Lower Mainland, the Ontario Association of Social Workers, and the Canadian Mental Health Association.",2020,-99,University of Victoria,,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,BC Ministry of Health | Canadian Institutes of Health Research (CIHR) | Michael Smith Foundation for Health Research,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10383,SE0558,Investigating zoonotic and reverse-zoonotic transmission of SARS-CoV-2,"Description SARS-CoV-2 emerged in 2019, causing coronavirus disease (COVID-19) and attaining pandemic status in March 2020. The origins of the virus likely include transmission from wild animals to humans, possibly via an intermediate animal. SARS-CoV-2 has transmitted from humans to several animal species (reverse-zoonosis), with animal-to-animal infection (reservoir) and zoonotic (animal-to-human) transmission in some instances (e.g. captive mink). However, uncertainty around transmission parameters for SARS-CoV-2 in the zoonotic and reverse-zoonotic context, and the spectrum of host range, remain to be fully elucidated.This proposal is a progression from our initial infection model investigations (SE0557) and will synergise, utilise and expand, on two SARS-CoV-2 Defra toolbox initiation projects. The overall aim is to further our understanding of zoonotic and reverse-zoonotic potential of SARS-CoV-2 infection Objective SARS-CoV-2 emerged in 2019, causing coronavirus disease (COVID-19) and attaining pandemic status in March 2020. The origins of the virus likely include transmission from wild animals to humans, possibly via an intermediate animal. SARS-CoV-2 has transmitted from humans to several animal species (reverse-zoonosis), with animal-to-animal infection (reservoir) and zoonotic (animal-to-human) transmission in some instances (e.g. captive mink). However, uncertainty around transmission parameters for SARS-CoV-2 in the zoonotic and reverse-zoonotic context, and the spectrum of host range, remain to be fully elucidated.This proposal is a progression from our initial infection model investigations (SE0557) and will synergise, utilise and expand, on two SARS-CoV-2 Defra toolbox initiation projects. The overall aim is to further our understanding of zoonotic and reverse-zoonotic potential of SARS-CoV-2 infection",2020,2021,Animal and Plant Health Agency (APHA),129652.74,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +C10384,AQ0850,COVID-19: Differential ethnic environmental behaviours and concerns,"Description This report presents findings from analysis of survey data from the Centre for Climate Change and Social Transformation (CAST) to explore whether respondents from Black, Asian and minority ethnic (BAME) groups experienced the COVID-19 lockdown differently to white respondents in regard to their environmental behaviours, attitudes and experiences. Objective The specific research objectives are to test whether there are meaningful differences in: Environmental attitudes and behaviours between BAME and white respondents since the outbreak of the COVID-19 pandemic; Wellbeing and worry about COVID-19 between BAME and white respondents; and Any change of environmental behaviours reported from before the pandemic to during the pandemic between BAME and white respondents.",2020,2020,N/A,,Human Populations,Asian | Black | White,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,,Europe,,,,,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C10463,COV20_00070,"Pilot, open, randomized clinical trial of combined use of Hydroxychloroquine, Azithromycin and Tocilizumab for the treatment of SARS-CoV-2 (COVID-19) infection","The main objective of the study is to evaluate in-hospital mortality, need for mechanical ventilation, or need for rescue doses of tocilizumab in patients with confirmed COVID-19 infection receiving hydroxychloroquine and azithromycin combined with hocilizumab. The study will compare 2 branches, usual therapy in clinical practice, control branch; vs. tocilizumab treatment, experimental branch.",2020,-99,Fundacio Privada Institut de Recerca de LÇîHospital de la Santa Creu i Sant Pa,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments, +C10464,COV20_00072,Multicenter Randomized Clinical Trial of Convalescent Plasma Therapy Added to Best Available Treatment for COVID-19 in Hospitalized Patients,"Hyperimmune convalescent plasma (CP) is commonly used in severe respiratory infections of viral origin, in emergency situations and based on low-quality non-comparative studies. Faced with the SARS-CoV-2 pandemic, we propose to carry out a randomized trial in hospitalized subjects with non-critical forms of COVID-19 with CP vs ""standard of care"" (according to WHO guidelines), in more than 20 hospitals, in coordination with the transfusion centers and the CNM-ISCIII, which will allow us to analyze with a high level of evidence the efficacy and safety of the treatment, including the risk of lung damage mediated by antibodies and immune response, as well as to evaluate its impact on the evolution of viral load and seroconversion (neutralizing antibodies) of patients, evaluate the feasibility of a model for the identification of donors and CP production for SNS patients, and guide decision-making on CP in COVID-19 at the national and international level.",2020,-99,FUNDACION PARA LA INVESTIGACION BIOMEDICA DEL HOSPITAL UNIVERSITARIO PUERTA DE HIERRO,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10465,COV20_00005,Pilot study to evaluate the efficacy and safety of mefloquine as prophylaxis in people exposed to the disease caused by coronavirus SARS-CoV-2 (COVID-19),"This is a multicenter, randomized, double-blind, two-arm clinical trial comparing the efficacy and safety of mefloquine versus placebo for prophylaxis against COVID-19 in close contacts of infected people. As well as establishing whether the preventive administration of mefloquine attenuates the clinical manifestations of COVID-19 in people who become infected, while seeking to evaluate the safety of prophylactic mefloquine in this scenario. To do this, 200 contacts of people in close contact with patients infected by COVID-19 will be selected and they will be randomly assigned to one or another arm of the study and who must follow the indicated administration schedule (one tablet to week)",2020,-99,Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10466,COV20_00023,Randomized clinical trial to evaluate the efficacy of different treatments in patients with COVID-19 requiring hospitalization,"There is an urgent need to evaluate the drugs currently in use and with potential efficacy for COVID-19 through clinical trials. This protocol evaluates the efficacy of various treatments in patients with severe SARS-CoV-2 pneumonia. The design of the study is an open, randomized CT that allows the addition / removal of treatment arms while the trial is ongoing in an adaptive way to the information that is generated in this study or in other available ones.",2020,-99,FUNDACION PARA LA INVESTIGACIÇÿN BIOMEDICA DEL HOSPITAL UNIVERSITARIO LA PAZ,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10467,COV20_00096,SEVOFLURAN SEDATION IN PATIENTS WITH RESPIRATORY DISTRESS SYNDROME CAUSED BY COVID19 INFECTION.,"TNF] alpha, IL-1beta, IL-6, IL-8) alveolar and plasma at the time of admission and on Day 2. The investigators who will perform the analyzes will be blind to the group assignment. This is an intention-to-treat test",2020,-99,FUNDACION PARA LA INVESTIGACION DE HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C10468,COV20_00122,Development of colorimetric sensors based on gold nanoparticles for the detection of SARS-CoV2,"The project addresses the preparation of colorimetric sensors based on nanoparticles and oligonucleotides, which allow detecting the presence of the virus by means of a change in the color of a solution, or the presence of color in a nitrocellulose strip. The system will be implemented in 3 different amplification systems in order to reduce the use of equipment, highly specialized personnel and reagents to a minimum: 1) in RT-PCR, avoiding the use of qRT-PCR, 2) in isothermal amplification, avoiding the use of PCR in general, and 3) in non-enzymatic amplification, avoiding the use of enzymes. The processes developed are industrially scalable, and it is expected to rapidly acquire the capacity at IMDEA Nanoscience to produce 5,000 nanoparticle-based sensors weekly.",2020,-99,Fundación Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-Nanociencia),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Innovation,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10469,COV20_00399,DEFIBROTIDE AS PREVENTION AND TREATMENT OF COVID-19 RESPIRATORY DISTRESS AND CYTOKINE RELEASE SYNDROME,"This project aims to demonstrate that DEF is effective and safe as a therapy for COVID-19. The goal is to decrease mortality by a rate of at least 25%. 120 patients with WHO COVID-19 grades 4, 5 and 6 will be included, who will be randomized 2: 1 to receive the experimental or control treatment respectively, and will be stratified according to the WHO classification into two groups: 40 patients WHO grade 4-5 will receive experimental treatment + standard treatment and 20 patients (control group) will receive placebo plus standard treatment, and 40 WHO grade 6 patients will receive experimental treatment + standard treatment, and 20 patients (control group) they will receive placebo plus standard treatment.",2020,-99,FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA (FFIS),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10470,COV20_00612,International randomized trial to evaluate unlicensed treatments for COVID-19 in hospitalized patients receiving conventional treatment for COVID offered in each hospital,"International randomized trial of adaptive design to evaluate unlicensed treatments for COVID-19 in hospitalized patients receiving conventional treatment for COVID offered in each hospital. Adults> 18a hospitalized with laboratory confirmed COVID-19 with no contraindication to study drugs or reason for not participating will be included. They will be randomized to: conventional TTo or conventional Tto plus one of the tested drugs (Remdesivir, Chloroquine / OHchloroquine, Lopinavir + Ritonavir or Lopinavir / Ritonavir + Interferon). Included patients are followed daily for the duration of treatment.",2020,-99,Fundación para la Investigación Biomédica del Hospital Clínico San Carlos-IdISSC,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments, +C10471,COV20_00050,Development of a vaccine against SARS-COV-2 using muNS-Mi micro / nanospheres,"We have developed and patented a methodology that allows cells of any origin to be programmed to build protein micro (MS) or nanospheres (NS) and introduce any protein of interest into them by tagging them with a tag called IC. These MS function as vaccines in the absence of adjuvants and the integrated proteins fold perfectly, allowing quaternary structures and even enzymatic reactions. In this project we intend to generate microspheres that contain the S1 domain of the S protein or the M or N proteins of SARS COV-2 and to characterize the immune response that they induce when administered intranasally or intramuscularly in a mouse model. The methodology is already developed in the expression systems of baculovirus, mammalian cells and bacteria, and will be adapted to the yeast system for its rapid implementation in human vaccines.",2020,-99,UNIVERSIDAD DE SANTIAGO DE COMPOSTELA,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity, +C10472,COV20_00279,DETECTION AND RAPID CHARACTERIZATION OF COVID19 AND THE PATIENT,"The life cycle of coronaviruses allows differentiation between the encapsulated virus and its infection and replication processes. We will develop modular kits that allow, on the one hand, to determine the presence of the virus, the presence of viral processes involved in the infection and the determination of those variables that may be relevant in the development of the disease (viral and human). The kits will be based on isothermal amplification and rapid PCR of the regions of interest and their rapid detection (15-30 minutes the presence of the virus, available in 1 - 2 months). In a second kit-module, from these amplified and those of interest in relation to the patient, libraries will be generated to be sequenced using Nanopore systems. This second part of the study will make it possible to know the strain of the virus and the variables of the patient that are relevant in the disease, making a report based on the available data and including other clinical variables of interest.",2020,-99,FUNDACION PARA LA INVESTIGACION DE HOSPITAL CLINICO DE LA COMUNIDAD VALENCIANA,,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C10473,COV20_00080,Proof of concept for rapid detection of surfaces contaminated by SARS-CoV-2 using multispectral holographic and optical analysis with artificial intelligence,"Currently there are no methods for detecting and visualizing the presence of the SARS-CoV2 virus on material surfaces. The design, development and evaluation of a portable prototype device (using existing optical technologies combined with artificial intelligence) is proposed for the rapid and non-contact detection, in-situ, of contaminated areas on surfaces. It is proposed i) combine multispectral images in the optical range (ultraviolet to thermal infrared) and terahertz, ii) use analysis methods through computational optics, interferometry and holography, iii) integrate the information through artificial intelligence, and iv) perform tests of laboratory and in polluted and clean environments.",2020,-99,UNIVERSIDAD DE SEVILLA,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10474,COV20_00173,Nanosensor-based diagnosis and rapid identification in solution of disruptors of the interaction of the SARS-Cov-2 virus with its cellular receptor (NANOCOMPETE),"There are few serological tests against SARS-Cov-2 and none that can be performed in solution. The proposed assay makes it possible to detect antibodies (Ab) and / or viruses from serum or plasma, without processing, and directly identify Acs that compete for the virus / receptor interaction (whose sera may be used in serum therapy). We will use samples from the identified patients to identify coding sequences for Acs variable regions with sufficient affinity to block virus / receptor interaction and we will develop CARs for the destruction of infected cells but regulatory CARs to specifically block the immune system, in those cases in which it is responsible for the pathogenesis of serious infections. Based on existing developments, we proposed the proof of concept of a nanosensor, which allows the analysis of samples by the general public and the sending of results by means of a smartphone.",2020,-99,FUNDACION PARA LA GESTION DE LA INVESTIGACION BIOMEDICA DE CADIZ,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10475,COV20_00505,Design of antivirals for SARA based on polypharmacology S0800099D,"It is essential to design antivirals capable of simultaneously inhibiting various coronaviruses, thus introducing a series of molecules that can act as the first line of shock in SARS-CoV-2 mutations and in future pandemics. For this, it is essential to locate targets with high similarity, well characterized structurally, and perform a virtual screening of millions of compounds, a task that is only possible with the massive use of supercomputing. With this objective, we have formed a team with extensive experience in the development and massive application of software in pharmacological studies, as well as in chemical synthesis and medical chemistry. The selected and synthesized compounds will be tested in different projects already underway (to which we will transfer the molecules): the Grifols-Irsicaixa consortium and the UK's national synchrotron center, Diamond.",2020,-99,Barcelona Supercomputing Center. CENTRO NACIONAL DE SUPERCOMPUTACIÇÿN,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Pre-clinical studies, +C10476,COV20_00820,STUDY OF THE PROTECTION OF BCG AND MTBVAC AGAINST SARS-Cov-2 IN PRIMATES,"Study of the prophylactic activity of the trained innate immunity induced by the live attenuated vaccine MTBVAC compared with BCG against SARS-CoV2 in the model of rhesus macaques (Macaca mulatta) at the Biomedical Primate Research Center (BPRC) in the Netherlands. The present investigation is part of the studies that the BPRC is going to begin on the protective activity due to the increase of the trained immunity induced by BCG against SARS-CoV2, studying the inoculation of the BCG vaccine by different routes of administration (intradermal, pulmonary and intravenous) and which co-finances this proposal at 50%.",2020,-99,UNIVERSIDAD DE ZARAGOZA,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10477,COV20_00155,EARLY DIAGNOSIS OF COVID-19 THROUGH THE ISOLATION OF EXOSOMES IN INDIVIDUALS SUSPICIOUS OF THE DISEASE.,"SARS-CoV-2 or Covid-19 is a new type of coronavirus that causes a serious respiratory infection. Following the WHO indications, it has been announced that new diagnostic tests will be used shortly, much faster, but also more imprecise that may give false positives and negatives. In addition, during the first moments of the infection, some patients were initially negative, despite being infected, with the subsequent transmission of the infection. Given that genetic material of coronavirus has been found in serum exosomes and HIV-1 in urine exosomes of infected people, here we suggest carrying out diagnostic tests on the exosomes of urine, plasma and saliva of patients at different times of the study, in order to detect it more reliably and earlier.",2020,-99,INSTITUTO ARAGONES DE CIENCIAS DE LA SALUD,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10478,COV20_00624,Molecular beacon design for rapid and efficient identification of SARS-CoV-2 RNA species in COVID-19 patient samples,"Due to the health emergency caused by the outbreak of the COVID-19 pandemic, and in the face of a possible rebound or chronic disease scenario, the development of tools that facilitate the detection and monitoring of patients susceptible to infection by the disease is urgently needed. SARS-CoV-2 virus. This project aims to generate an alternative, rapid and sensitive test for the direct detection of virus RNA species from human samples, in order to simplify the times, costs and experimental complexity required for the current diagnosis of COVID -19. To this end, this proposal contemplates the design of a battery of fluorescent molecular beacons and the use of scalable fluorimetric analysis through the use of signal amplification technology by nicking enzyme (NESA), in order to carry out a direct identification. , effective and low cost of different species of coronavirus RNA in human samples.",2020,-99,"AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS, M.P.",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10479,COV20_00823,Rapid serological testing for combined detection of IgG and IgM against SARS-CoV-2,The project aims at the development of a rapid and easy-to-use serological test for the screening of COVID-19 and the differentiation between current and past infections. The addition of fingerprick blood sample and a final immersion of dipstick/addition of substrate is the only required end-user intervention. It is based on the detection of the IgM and IgG antibodies produced by infected person's immune system to fight the infection. The assay design will diffe from the common format used by numerous manufacturers to eliminate the possibility of false negative results. Gold and carbon nanoparticle labels will be used for visual readout and the specific colour combination on the strips will be related to the presence of specific antibody type. A recombinant COVID-19 antigen will be prepared for the final preparation of prototype tests to be validated using patient blood samples. The assay time will be less than 15 minutes and the production cost will be ca 1€,2020,-99,UNIVERSITAT ROVIRA I VIRGILI,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C10480,COV20_00565,"Prevention of COVID19 infection by administration of hydroxychloroquine in institutionalized elderly and nursing home care personnel. Controlled, open and randomized stepped-wedge clinical trial by clusters","Objective: To evaluate the effectiveness of chemoprophylaxis with hydroxychloroquine in healthcare personnel and residents: a) on the incidence of secondary cases of SARS-CoV-2 infection in residents, and b) on the incidence of SARS-CoV-2 infection in the staff themselves . Evaluate the effect of measures to promote infection control. Design: Staggered, randomized, open-label, controlled study. Subjects: institutionalized elderly and direct care professionals in 4 Autonomous Communities. Sample: 880 professionals, 1050 residents in 84 residences. They will be given 800mg of HCQ on the first day and 400mg for four days. Nasopharyngeal swab will be taken for baseline RT-PCR, 6 and 14 days and baseline serology and 28 days. Mortality, compliance, safety, symptoms, admission and viral load will be evaluated secondarily.",2020,-99,FUNDACION PARA LA INVESTIGACION DE MALAGA EN BIOMEDICINA Y SALUD (FIMABIS),,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Health Personnel | Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Epidemiological studies | Therapeutics research, development and implementation",Disease surveillance & mapping | Prophylactic use of treatments, +C10481,COV20_00021,EPIDEMIOLOGICAL REGISTRY OF PREGNANT WITH COVID 19,"Spanish multicenter epidemiological study based on the registry of cases of pregnant women with COVID 19 in Spain Objective to know the influence of COVID 19 on pregnancy and delivery in our country. 77 Associated centers at the time of preparing this document. Database that complies with data protection law This is a prospective observational registry study of pregnant women suspected of having a SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV -two. Follow-up up to two weeks after delivery. Start date March 2020 End March 2021 € 43,000 is requested to create its own database, exploit it and communicate the results",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL PUERTA DE HIERRO,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics, +C10482,COV20_00027,Use of drugs that increase the expression of ACE2 and risk of COVID-19: A case-population study.,"SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) to penetrate cells and replicate. It is known that certain drugs increase the expression of ACE2 and could facilitate the entry of the virus and increase the severity of the infection. It is intended to carry out an epidemiological study of cases and controls, taking as cases the patients hospitalized for COVID-19 in the participating hospitals (subclassified by severity) and primary care population controls extracted from the BIFAP database and matched with the cases by age. (exact), sex and index date. Information on prescribed drugs and comorbidities will be extracted from hospital and Bofap medical records, and the adjusted Odds Ratio will be computed using conditioned logistic regression models. The extraction of information from mild COVID-19 + cases not hospitalized as an alternative series of controls (ratio 1: 1) will be considered.",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSP. PRINCIPE DE ASTURIAS,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease susceptibility, +C10483,COV20_00040,"Short, medium and long-term effect of Coronavirus disease 2019 on the cardiovascular system.","Patients with COVID-19 disease have a very high risk of short-term and long-term adverse cardiovascular events, including death from cardiovascular causes. We propose an epidemiological surveillance study to determine the rate of adverse cardiovascular events (cardiovascular death, myocardial infarction, cardiovascular accident, cardiac arrhythmias = at the time of infection, 30 days, 6 and 12 months, in patients confirmed by COVID- 19. In addition, to determine the relationship between the use of angiotesin-2-converting enzyme inhibitors, angiotesin-2 receptor blockers, and non-steroidal anti-inflammatory drugs in the presentation of severe or fatal symptoms due to COVID-19. Through a case-control study We will develop early warning tools, prediction and risk stratification of adverse cardiovascular events in patients with COVID-19. Through a web page, the information generated will be immediately disseminated and the tools developed will be openly used.",2020,-99,INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C10484,COV20_00108,COVID-19 infection in HIV-infected patients included in CoRIS,"To date, only anecdotal cases of COVID-19 have been described in HIV-infected people. This supports the hypothesis that antiretroviral drugs might have some protective effect against SARS-CoV-2 infection. In order to have reliable information about the incidence of symptomatic or asymptomatic SARS-CoV-2 infection, we intend to carry out a retrospective study within the scope of the Cohort of the Spanish AIDS Research Network (CoRIS). Objectives: (i) describe the frequency and epidemiological and clinical characteristics of patients with COVID-19 in CoRIS, as well as the prognostic factors for the requirement of intensive care, use of mechanical ventilation, length of stay and mortality; and (ii) Study the prevalence of antibodies against SARS-CoV-2 by determining IgG and IgM antibodies by ELISA",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL GREGORIO MARAÑON,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease surveillance & mapping | Prognostic factors for disease severity, +C10485,COV20_00110,"Risk factors, personalized prognosis and one-year follow-up of patients admitted to the Spanish Intensive Care Units infected by the COVID virus: CIBERSESUCICOVID","The project presented has the objective of knowing the risk factors and prognosis and short and long-term outcomes (6 months and one year) of patients with COVID19 admitted to Spanish ICUs. Two other additional objectives are the epigenetic study and essential predictive enrichment biomarkers to help individualize treatment based on the altered biological pathways in each patient. CIBERES has the endorsement of SEMICYUC and SEPAR. The hypothesis at the end of the pandemic that 10,000 patients will have been admitted to the Spanish ICUs selected through SEPAR and SEMICYUC. The clinical data will be analyzed with artificial intelligence. An interim analysis will be made with the first 1000 patients, which may be useful for the clinical management of patients with severe COVID19.",2020,-99,CONSORCIO CENTRO DE INVESTIGACION BIOMEDICA EN RED (CIBER),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences, +C10486,COV20_00156,NGS ANALYSIS OF THE OUTBREAK OF SARS-COV2 OF THE GENERAL HOSPITAL OF ELCHE,"Molecular study using the NGS technique to obtain the genome sequences of the SARS-Con2 virus from the positive cases identified in the Health Department of the Valencian Community. With the data obtained, a molecular epidemiological analysis of the genetic variation of the virus in this department can be carried out from the beginning of the outbreak until its end. In addition, these sequences will contribute to increase the genomic sequences of this virus in world databases that will allow epidemiological studies to be carried out both nationally and worldwide. With the information generated, it can be put into context with the clinical data of the patients affected by the SARS-CoV-2 infection and it will be possible to identify if there is any relationship or any cluster of the virus with the highest prevalence or worst prognosis in our department. of health.",2020,-99,FUNDACION PARA EL FOMENTO DE LA INV. SANITARIA Y BIOMEDICA DE LA COMUNIDAD VALENCIANA (FISABIO),,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis", +C10487,COV20_00157,Neurological involvement in clinically relevant Covid-19 disease. Does Neuro-Covid-19 disease exist?,"1]. On the other hand, in a retrospective review of 214 cases assisted during the epidemic outbreak in Wuhan, symptoms attributable to both the CNS and the PNS are described in a relevant percentage (Mao L et al MedRxiv 2020.02.22.20026500). Based on these data, we establish the hypothesis that neurological involvement in the acute phase and in the medium or long term may condition the prognosis and quality of life in patients surviving the infection. The objective of this project is the clinical, biological and molecular characterization of neurological involvement in a prospective cohort of patients surviving SARS-CoV-2 infection.",2020,-99,FUNDACION PARA LA INVESTIGACION DE MALAGA EN BIOMEDICINA Y SALUD (FIMABIS),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C10488,COV20_00170,"Search for immunological, prognostic and therapeutic markers in patients with COVID-19","Our primary objective is the study of the innate and acquired immune response in patients diagnosed with SARS-CoV-2, by monitoring the cellular and humoral components of the innate and adaptive immune response in blood and its correlation with clinical severity. This panel is similar to the one used in the clinical characterization of immunosuppressed patients and can be applied immediately to the management of the patient with COVID-19.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION MARQUES DE VALDECILLA (IDIVAL),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10489,COV20_00181,"STOP-Coronavirus: Clinical, Immunological, Genomic, Virological and Bioethical Factors of COVID-19","WPs]) over 12 months: WP0 (cross-sectional): constitution of a prospective cohort of patients with COVID-19, clinical characterization and collection of biological samples (HU12O, HUFJD / IIS-FJD, HCUVA, HUIE); WP1 (clinical): predictive model based on clinical and biochemical variables (HU12O); WP2 (immune): immune response to SARS-CoV-2 (HU12O, HCUVA); WP3 (genomic): host genetic prognostic markers (HUFJD / IIS-FJD, HCUVA); WP4 (immunosuppressed): COVID-19 in oncohematological and transplant patients (HU12O, HUFJD, HCUVA); WP5 (therapeutic): response to antiviral and immunomodulatory treatment (HU12O); WP6 (bioethical): socio-economic analysis and ethical repercussions (HUIE, HUFJD, HCUVA); and WP7 (virological): viral dynamics and spectrum of SARS-CoV-2 mutants.",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL 12 DE OCTUBRE,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other | Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Research to inform ethical issues | Secondary impacts of disease, response & control measures","Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts", +C10490,COV20_00188,Gestation and COVID-19: clinical and microbiological study (GESTA-COVID19),"Objective: The main objective of this study is to describe the influence of pregnancy on COVID-19 infection, as well as the influence of COVID-19 (and its treatment) on pregnancy, the fetus and the newborn. Methods: This is a descriptive, observational longitudinal and multicenter study consisting of 8 hospitals: H. U. Vall d'Hebron (Barcelona) and H.U. La Paz (Madrid), H.U. Virgen de la Arrixaca (Murcia), H.U. Cruces (Bizkaia) and H.U.C. Lozano Blesa (Zaragoza), San Cecilio University Hospital (Granada), H.U. La Fe (Valencia), H.U. Torrejón (Madrid). It will take place between April 2020 and March 2021. An electronic data collection notebook (REDCap) will be designed where the data will be entered anonymously. Pregnant women infected with SARS-CoV-2 will be included, microbiological samples from the mother and the newborn will be collected and processed (PCR-SARS-CoV-2 in a delayed manner) and clinical data related to the patient, the infection, its treatment and complications. , pregnancy and complications, childbirth and the newborn. The results will be disclosed to the scientific community, society and health authorities.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION VALLE DE HEBRON,,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C10491,COV20_00227,SARS-CoV-2 INFECTION IN PATIENTS WITH INFLAMMATORY DISEASE,"Objective: To evaluate: 1) the incidence, clinical presentation, severity and mortality of CoVid19 in the epidemic period (5 months). 2) the evolution of patients under immunosuppressive and / or biological treatment compared to those who do not receive it 3) Clinical, demographic, epidemiological factors associated with the risk of contracting the infection and presenting poor evolution 4) influence of COVID infection -19 in the evolution of Eli and its treatment one year after infection.",2020,-99,FUNDACIÇÿ DOCÇ?NCIA I RECERCA - MǸTUA TERRASSA,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis, +C10492,COV20_00236,Study of the Microbiome and Viroma associated with CoVid19 disease,"Infection by this virus ranges from asymptomatic forms to very severe bilateral pneumonias that frequently cause the death of the patient. The microbiome and virome are altered in a large number of pathologies, but their involvement in this process is unknown although it is possible that both are involved in the different clinical severity of the patient. Therefore, it is proposed to carry out the study of the microbiome and the virome through a bioinformatic and statistical analysis of the microbial diversity and the taxa present in each of the samples, in order to identify biomarkers severity of the process that can be used to better manage the patient.",2020,-99,FUNDACION DE LA COMUNIDAD VALENCIANA PARA LA GESTION DEL INST. INV. SANIT. Y BIOMEDICA DE ALICANTE,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C10493,COV20_00310,Ultrasound follow-up in pregnant women with COVID-19 infection. Risks associated with severe infection and the trimester of pregnancy.,"The implications of the COVID-19 pandemic on pregnancy are not well known. Severe maternal infection can be associated with premature delivery or fetal growth retardation. Maternal hypoxia could have consequences on neurodevelopment and at the fetal heart level. On the other hand, there are no data on the repercussions of COVID-19 infection according to the trimester of gestation. Our objective is to analyze the perinatal outcome and the risk of growth retardation, abnormalities at the level of neurosonography or fetal echocardiography in women with COCID-19, as well as associated factors (severe maternal infection, hypoxemia, gestational age at infection). The expected results can be very useful to advise on possible fetal risks, improving care and the pregnancy experience.",2020,-99,INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS,,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C10494,COV20_00314,Immunosenescence as a risk factor for SARS-CoV-2 infection,"In this project we intend to make a rapid approach to the status of lymphocyte populations and the inflammation process in positive COVID19 patients with and without symptoms compared to negative COVID19 patients. With the hypothesis that immunosenescence is playing a role in the susceptibility to being infected, the studies will be carried out in different age ranges (30-40 / 40-50 / 50-60 / older than 60). In the case of COVID19 positive patients, the immunosenescence and inflammation profiles at the time of diagnosis will be correlated with the clinical variables for monitoring the disease in search of prognostic markers of evolution.",2020,-99,ASOCIACION INSTITUTO BIODONOSTIA,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10495,COV20_00324,Functional characterization of SARS-CoV-2-specific T and B cell long-lasting Immunity in immunocompetent and immunosuppressed patients developing SARS-CoV-2 infection (COV-Immunity),"In this project we will investigate, using highly sensitive immune assays, the development of short and long-lasting immunity, both humoral and cellular, specific against SARS-cOv-2, at the time of infection and at different time points afterwards up to 24 months in previously healthy individuals, patients with relevant co-morbidities, solid organ transplant patients receiving chronic immunosuppression and patients with malignancies receiving chemotherapy.",2020,-99,FUNDACIÇÿN INSTITUTO DE INVESTIGACIÇÿN BIOMEDICA DE BELLVITGE (FUNDACION IDIBELL),,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10496,COV20_00377,Role of NK cells in the susceptibility and prognosis of SARS-CoV2 (COVID19) infection,"The project investigates the role of NK cells in the susceptibility and prognosis of SARS-CoV2 (COVID19) infection. In patients with mild (n = 100) and severe (n = 100) disease, the genotype (PCR-SSO-Luminex) and the expression in NK cells (12 Fluorescence cytometry) of the KIR / ligand-HLA-I interactions that regulate the education and function of these cells and determine their effectiveness against viral infections. The data will be contrasted with 600 healthy controls of known genotype. The results would contribute to optimizing health resources and avoiding collapse by facilitating: 1) accentuating protection efforts in the most susceptible people (health professionals, law enforcement officials, relatives of the sick, etc); and 2) anticipate anti-viral and anti-inflammatory therapies at the appearance of the most serious symptoms in susceptible patients.",2020,-99,FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA (FFIS),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10497,COV20_00385,Derivation and validation of a prognostic scale in COVID-19 pneumonia. National multicenter study,"CSI] from a multicenter database in patients with COVID-19 pneumonia with prognostic variables of severity at admission to predict ICU requirement and death . A retrospective and multicenter study will be carried out of adult patients with COVID-19 pneumonia who require hospitalization in hospitals throughout the Spanish geography (it is estimated to recruit about 4,000 pneumonia).",2020,-99,FUNDACION PARA LA INVESTIGACION DEL HOSPITAL LA FE,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Prognostic factors for disease severity, +C10498,COV20_00386,Impact of monoclonal B lymphocytosis and the state of the immune system on the development and evolution of COVID-19 infection in adults,"In this project we start from the hypothesis that patients infected by the SARS-CoV-2 virus carry an aging immune system -determined by the presence of small clones of circulating B cells in peripheral blood and the secondary immunodeficiency associated with this condition- , they would develop a more serious disease and would evolve worse due to their inability to recognize new antigens. To do this, we propose: 1) to explore the presence of B lymphoid clones (LBMlo) in the blood of infected patients admitted to the Internal Medicine Department of the University Hospital of Salamanca; 2) study the state of your immune system, using innovative tools developed by the research group that allow identifying> 250 different populations of immune cells in blood; 3) relate the above data with the clinical characteristics of the patients; and 4) identify parameters related to an aging immune system that will provide a solid basis for prognostic stratification, and clinical validation.",2020,-99,FUNDACION INSTITUTO DE ESTUDIOS DE CIENCIAS DE LA SALUD DE CASTILLA Y LEON,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10499,COV20_00004,Clinical-epidemiological study of coronavirus disease (COVID-19) in health centers: COVID-A study,"The objective is to carry out a clinical-epidemiological study as broad as possible in nursing homes for the elderly in Albacete province to analyze their clinical, sociodemographic, functional, cognitive, nutritional and geriatic syndromes characteristics, identify factors predisposing to infection and health outcomes. specific in this high-risk population. Initially, it will be held in the ""Vasco Núñez de Balboa"", ""Paseo de La Cuba"", ""Vital Parque"", ""Alcabala"" and ""Alábega"" residences for the elderly, although it could be extended to other residences. In total, it is expected to include around 1000 residents. A follow-up will be carried out at 3 and 6 months to collect clinical, epidemiological and economic outcome variables in collaboration with the Department of Economic Analysis of the UCLM (Toledo). The study will be carried out in the Albacete Geriatric Service.",2020,-99,Servicio de Salud de Castilla-La Mancha (SESCAM),,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C10500,COV20_00047,Therapeutic repositioning aimed at inhibition of ACE2 expression and proteolysis of viral S trimer,"Several cell lines (eg Vero or Calu-3) express in their cell membrane the protein ACE2, which participates in the union with the S trimer of SARS-Cov-2, and also presents proteolytic activities for the activation of the same protein, two of the hypothetical requirements for entry of the virus into the human host. According to her, those substances that can decrease the role of ACE2 or the activity of host proteases on protein S, could be used for the treatment of infarction. Thus, i) commercial drug libraries authorized for use in humans and ii) antisense oligonucleotides with peptide vahicles will be used as molecules as a new therapeutic approach.",2020,-99,INSTITUTO INV. BIOMEDICA DE LLEIDA. FUNDACION DR. PIFARRE (IRBLLEIDA),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C10501,COV20_00086,PsyCorona: a multinational initiative of urgent data collection with a longitudinal and prospective approach,"We are conducting a rapid, multi-national collaboration that aims to identify psychological and cultural factors that may be relevant to the virus spread and its imminent social and material consequences. The online survey includes brief measures to assess topic-relevant beliefs, fears, hopes, and frustrations, predictors of self-containment and social distancing, attitudes toward policies, reasoning, and behavioral self-reports. The survey has a built-in longitudinal component as well as a broader data science mission involving metadata. This is an unfunded, citizen-scientist initiative comprised of 40+ colleagues (and counting). The goal of group is to publish reports suggesting to policy makers the most promising avenues to thwart the spread of the virus.",2020,-99,UNIVERSIDAD DE CÇÿRDOBA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C10502,COV20_00121,Identification of the dynamic transcripomic profile in patients with COVID-19 and acute respiratory distress syndrome (TRANSCOVID),"Although some clinical characteristics (advanced age, high fever, SOFA) and inflammatory response (IL-6, PC-R, D-dimer) have been described, the reasons why certain patients with COVID-19 develop severe disease, presenting dyspnea and hypoxemia in the first 7 days and rapid progression to ARDS, multiple organ failure and death, they still remain an enigma. The main objective of this project is to determine the dynamic transcriptomic profile of adult patients hospitalized for COVID-19 and to characterize the subgroup that develops severe disease (ARDS). Secondary objectives are to establish a gene signature capable of basal discrimination of the group that will develop ARDS and contribute to the phylogeny of the virus.",2020,-99,FUNDACIÇÿN INSTITUTO DE INVESTIGACIÇÿN BIOMEDICA DE BELLVITGE (FUNDACION IDIBELL),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C10503,COV20_00140,Addressing unknowns of COVID-19 transmission and infection combining pathogen genomics and epidemiology to inform public health interventions,"There is a growing pressure to understand the transmission patterns of COVID-19. As a new, emergent virus we have important gaps in the epidemiology of its infection. Those gaps translate also to limited understanding on who is infectious and for how long and how is connected to clinical outcome. Here we propose several objectives that involve combining viral genome data to epidemiological, clinical information to address those gaps. We will obtain viral complete genome sequences and epidemiological data and combine to (1) inform public health measures by revealing highways of transmission; (2) identify when an individual is infectious; (3) identify early warnings of local spread; (4) viral diversity connected to immune, drug and diagnostic; (5) complement current diagnostic approaches, and (6) identify the connection to adverse clinical outcomes. To this end, we have put together a nation-wide group of infectious disease, genomics, bioinformaticians and clinical researchers from more than 30 institutions.",2020,-99,"AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS, M.P.",,Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease pathogenesis", +C10504,COV20_00151,"Development of a vaccine, MVA-COVID-19, expressing SARS-CoV-2 antigens","Our objective is to produce an effective vaccine against SARS-CoV-2 as follows: Vaccine 1: This vaccine named MVA-COVID-19(S) will express the full-length S protein of SARS-CoV-2 and is directed to generate in an organism neutralizing antibodies to prevent infection and virus spread. This vaccine is ongoing in our laboratory and expected to have the candidate during April-May 2020 to be used for preclinical studies during June-July 2020. Vaccine 2: This vaccine named MVA-COVID-19(S-E-M) will express three proteins of SARSCoV-2 (S, E and M) in the form of VLPs and is directed to trigger neutralizing antibodies and T cell (CD4+ and CD8+) immune responses, with the goal to produce long-term control of virus infection. This vaccine will be generated along May-September 2020 to initiate the preclinical studies in October-December 2020.",2020,-99,AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTÇ?FICAS M.P.,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Vaccines research, development and implementation",Pre-clinical studies, +C10505,COV20_00183,An innovative therapy against Covid-19 based on circular RNAs,"Given the speed with which we can sequence the genomes of new RNA viruses, developing targeted therapies against them, rather than against viral proteins, would accelerate the development of efficient therapies. In this project we will generate and validate, in cell culture and in mouse models, circular RNAs (ARNcircs) that hybridize and interfere with essential structures in the SARS-CoV-2 genome and inactivate it. The selection of resistances is highly unlikely given the conservation of the target sequences and the interference on several regions simultaneously. Our previous success with ARNcircs that inhibit the replication of other RNA (+) viruses, and the existence of RNA-based therapies already in the clinic and of nebulization delivery systems, support the viability of our proposal.",2020,-99,Universidad Pompeu Fabra,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C10506,COV20_00214,Preclinical development of innovative mRNA / MVAvaccines against SARS-CoV2,"The purpose of this project is to design and test in preclinical studies a new vaccine against SARS-CoV2.The overall objective: 1. In a first step, to test a new mRNA vaccine candidate encoding SARS-CoV2epitopes selected through a bioinformatic approach and co-formulated with nanoparticles (mRNA-CoV2) in vitro and in vivo to assess the potential to induce SARS-CoV2-specific immune responses. 2. In a second step, to test if a prime-boost strategy with mRNA-CoV2 prime and MVA-CoV2 boost induce higher immune responses as compared with mRNA-CoV2 alone.",2020,-99,INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS),,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Vaccines research, development and implementation",Pre-clinical studies, +C10507,COV20_00237,Development platforms for biosafe vaccines against SARS-CoV-2,"A biosafe vaccine engineering platform against SARS-CoV-2 will be established, including three production procedures. The first will use human cells secreting virus-like particles (VLPs), through the constitutive expression of the S, M and E proteins of SARS-CoV-2. The second will use baculoviral vectors for the expression of these genes on a large scale and to compare the production of VLPs. The third will be based on the production of non-replicative and non-integrative lentiviral particles, pseudotyped with the SARS-CoV-2 protein S and expressing the rest of the structural proteins. These particles will deliver the B and T epitopes to the immune system in a VLP format. BIRB796 will be incorporated into vaccine preparations to enhance the human T response, since it is a p38 MAPK inhibitor approved for human use and has anti-senescent properties in lymphocytes.",2020,-99,FUNDACION MIGUEL SERVET-NAVARRABIOMED,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Vaccines research, development and implementation",Pre-clinical studies, +C10508,COV20_00297,An Efficient Peptide Vector for mRNA Vaccination Against COVID19,"In the race to find a COVID-19 vaccine, gene-based approaches are the leading choice with some already ongoing clinical trials. However, the major challenge of this technology is the extreme sensitivity and the very low cellular uptake of the gene material that triggers the hosts' immune response, which hampers their potential. To overcome this limitation, we have developed a synthetic platform for the rapid screening of peptide amphiphiles with potential as gene delivery vehicles. approach allowed the identification of a candidate with a remarkable (one order of magnitude in vitro) improvement in delivery efficiency and cellular toxicity compared to typical commercial reagents. Remarkably, this candidate has also recently proven highly active for in vivo delivery of mRNA in mice, which suggests that it can be an excellent non-viral vector for the formulation of mRNA vaccines with a boosted potency, due to the uptake enhancement provided by this conceptually-new delivery vector.",2020,-99,Universidad de Santiago de Compostela,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Vaccines research, development and implementation",Pre-clinical studies, +C10509,COV20_00308,Analysis of soluble markers of immune activation and populations of CD8 NK and T cells in patients with SARS-CoV-2 infection,"This study aims to generate knowledge about the populations of immune cells in charge of infection control, in order to understand the kinetics and magnitude of the immune response during the COVID-19 disease. This knowledge can identify biomarkers that contribute to: 1) identifying which patients will be more likely to experience respiratory failure requiring admission and respiratory support treatment in intensive care units, 2) monitoring the evolution of the infection, and 3) exploring new therapeutic interventions. All this not only seeks to contribute to personalizing the treatment based on the profile and immune response of each patient, but it will also result in a reduction of the stress of the health system by being able to predict in advance the patients who may develop more serious clinical pictures and therefore plan and optimize the use of the resources available by the health system",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION SANITARIA ARAGON,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies, +C10510,COV20_00357,Prevalence of COVID-9 in patients with chronic inflammatory arthritis under treatment,"Patients with chronic inflammatory arthritis (CIA) have an increased risk of infections both due to dysregulation of the immune system and immunosuppressive treatment. Preliminary evidence in our department indicates a lower rate of infection by SARS.CoV-2 in patients with CICs receiving immunosuppressive treatment than that reported for the general population (<1%). This is a cross-sectional study of a very well characterized cohort of N = 1,175 patients with CIC receiving treatment with selective immunosuppressants (ISS), both adults as in pediatric age, followed systematically in a third-level university hospital. Epidemiological and clinical data will be obtained from the electronic medical record, the shared medical record of Catalonia and through a telephone survey. The prevalence and expression will be determined. clinical practice of COVID-19 in these patients, which will allow establishing clinical practice recommendations with great scientific and social impact.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION VALLE DE HEBRON,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,"Disease transmission dynamics | Supportive care, processes of care and management", +C10511,COV20_00370,Multicenter study of coronavirus disease 2019 (COVID-2019) in Solid Organ Transplant Recipients,"No information exists regarding COVID-19 in solid organ transplant recipients (SOTR). Besides, treatment is challenging as drug interactions might have an important impact on drug toxicity, graft dysfunction and rejection and probably outcome is adverse. No specific recommendations regarding COVID-19 exist. Objectives: to better understand the incidence, risk factors, clinical manifestations and outcome of COVID19 in SOTR. The results obtained will allow us to gain insight on the need of antiviral treatment, on the strategy for complications surveillance, on how to adjust the immunosuppressant therapy and on the level of care in which each patient should be treated. Design: Multicenter prospective study of consecutive cases of COVID-19 in SOTR. There will be a clinical follow-up of the patients included in this study to observe possible complications and survival rate.",2020,-99,FUNDACION PUBLICA ANDALUZA PARA LA GESTION DE LA INVESTIGACION EN SALUD DE SEVILLA,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis, +C10512,COV20_00401,Residual pulmonary fibrosis and lung capacity in survivors of SARS-CoV-2,"After the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic (2003/2003), many of the survivors developed residual pulmonary fibrosis (PF). Autopsies of these SARS patients showed the presence of pulmonary fibrosis at different stages of infection. Risk of PF was higher in older people, and was correlated with clinical severity and disease duration. On the other hand, lung biopsies showed dysregulation of the inflammatory response, the serum levels of certain pro-inflammatory cytokines being especially elevated. Furthermore, SARS-CoV infection induces an overactivation of the TGF-􀑛 pathway leading to pulmonary fibrosis.",2020,-99,FUNDACION RIOJA SALUD,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10513,COV20_00404,Prognosis of patients infected by the new coronavirus SARS-CoV-2,"Because approximately 14% of patients infected by SARS-CoV-2 present severe clinical pictures and 5% require critical care, the advance of the virus is causing an overload in the health system. In this context, the use of Predictive models to identify the most vulnerable subjects becomes a priority objective.Using data collected from electronic health records, this project aims to: 1) build survival and classification algorithms to estimate the risk of patients; and 2) based on the treatments administered to the patients, through the use of causal inference models, to quantify the effectiveness of the drugs according to the characteristics of the patients.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION SANITARIA DE SANTIAGO DE COMPOSTELA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management", +C10514,COV20_00420,COVID-19 in patients with HEART FAILURE AND FAMILY HEART DISEASE,"An online platform will be created to register cases of patients with previous heart failure or familial heart disease in which CoViD19 infection is confirmed. It will be an anonymized record that will be accessed with a username and password through the Web and will include basic demographic data, previous diagnoses, symptoms, previous and during the episode treatments, necessary interventions during admission and events. A common database will be generated from which the grouped data can be viewed and the corresponding statistical analyzes performed. The data will be available from the beginning of the project for the health authorities and for the participants in the registry. The registry will remain active for at least 2 years to be able to collect data retrospectively from patients undergoing previous follow-up in consultations, and for the incorporation of information on evolution and complications in the short and medium term.",2020,-99,FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA (FFIS),,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Data Management and Data Sharing,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C10515,COV20_00421,Epidemiological study and clinical-molecular implications of angiotensin in the prognosis of SARS-Cov-2 infection,"Epidemiological study and expression of polymorphisms in patients with COVID-19 infection under treatment with ACEI or AIIRA. The aim is to establish the association and the impact between COVID-19 infection and chronic treatment with ACEI or AIIRA, in terms of a torpid-fatal clinical course. These drugs increase the expression of ECA2, a vehicle for entry to target cells in SARS CoV / SARS CoV-2 acute respiratory syndrome. The aim is to establish the relationship between viral load and genetic predisposition by identifying polymorphisms and their expression linked to this enzyme, related to diseases such as: diabetes, hypertension and stroke and their treatments; trying to develop clinical trials to identify more efficient therapies in a population with high mortality.",2020,-99,Instituto de Investigación Sanitaria Biocruces Bizkaia,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis", +C10516,COV20_00429,Interaction between SARS-COV-2 and the human respiratory epithelium: sequestration of endocytosis and exocytosis pathways,"The entry routes of a pathogen into our body is based on the breakdown of our physiological barriers. In the case of the respiratory tract, the epithelium is one of the first barriers that the human body presents. The viral transfer of this epithelium has two alternatives: 1) the paracellular space, which would imply the disassembly of the tight and adherent junctions between neighboring cells, and 2) carrying out an intracellular transport process, taking the virus for its benefit the routes of intracellular traffic. This project aims to 1 study how the virus enters our body through the epithelial cells of the human respiratory tract. On the other hand, the release of new viruses to the lumen of the respiratory tract may be due to the exocytosis of the viruses. This process would require the use of the secretion pathways that cells use naturally. This project in its objective 2 will study the exocytosis of SARS-CoV2 in epithelial cells of the human respiratory tract. In addition, the development of Objectives 1 and 2 will conclude with the development of two screening platforms, allowing the search for drugs that block the entry or exit of the virus directly in respiratory tract epithelia.",2020,-99,Universidad de Extremadura,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis", +C10517,COV20_00459,CLINICAL CHARACTERIZATION OF COVID19 INFECTION: PROGNOSIS STRATIFICATION AND COMPLICATIONS,"Objectives: 1.-Create risk stratification scales of poor evolution in patients infected by CoVid19, and evolutionary profile of the patients; 2.-Assess effectiveness of treatment and diagnostic tests; 3-Evaluation of accessibility, equity, variability and costs Methods: Information extracted manually / automatically from the electronic medical record of parameters such as epidemiological antecedents, onset of symptoms, clinical manifestations, tests performed, treatments and evolution up to 3 months after discharge. Statistical analysis: using classic survival models, regression logistics, generalized linear models and also analysis using artificial intelligence techniques that assess the risk of poor evolution. Health care costs are assessed. Applications for decision-making will be derived as a product",2020,-99,ASOCIACION INSTITUTO DE INVESTIGACION EN SERVICIOS DE SALUD-KRONIKGUNE,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Health Systems Research","Diagnostics | Prognostic factors for disease severity | Supportive care, processes of care and management | Health financing", +C10518,COV20_00470,Effect of drug use before and during SARS-COV-2 infection on the evolution of patients with COVID-19. A population-based cohort study.,"There are important inconsistencies and lack of evidence on the effect of treatment with antihypertensive drugs of the ACEI and / or AIIRA type and some NSAIDs could be a risk factor for severity and even mortality from COVID-19. This favors rumors and errors in information, which can negatively affect Public Health and decision-making. Therefore, with this study we intend to assess whether the previous consumption of certain medications (ACEIs, ARA 2 conditions a greater susceptibility to infection by SARS-COV-2; and to identify those treatments received before and after the infection that are associated with a better evolution and greater survival.For this, Galician population registers will be used, through the HEXIN big data platform.",2020,-99,FUNDACIÇÿN INSTITUTO INVESTIGACIÇÿN SANITARIA DE SANTIAGO DE COMPOSTELA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments", +C10519,COV20_00519,FORECAST VARIABLES. RESOURCES CONSUMED AND HOSPITAL COST OF PATIENTS ADMITTED FOR SARS-COV-2 INFECTION ACCORDING TO THEIR FRAGILITY,"At the present time, COVID-19 has generated the greatest public health crisis, putting the health care system at serious risk of collapse. Thus, in mid-March it was necessary to resort to the national state of emergency and impose a home confinement that will continue at least until mid-April, with great chances of an extension. During this time, all the services of our hospitals, and especially the emergency and intensive care services, leave completely healthy, exceeding 100% of the existing capacity. In this authentic chaos, tents and pavilions are being set up to be able to attend the increasing number of patients with mild, moderate or severe symptoms of the disease. In addition, the prognostic, as well as the clinical presentation, is highly variable, with no empirical evidence to corroborate these differences. In this project we want to stratify the infected population according to different stages of frailty, in order to study the difference in evolution as well as in the use of hospital resources.",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL LA PAZ,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management | Health Systems Research,"Disease pathogenesis | Supportive care, processes of care and management | Health financing", +C10520,COV20_00527,Retrospective cohort study to evaluate the effect of NSAIDs and ACE inhibitors on the prognosis of symptomatic patients with COVID-19.,"To determine if patients with confirmed SARS-CoV-2 infection, treated with drugs that increase the expression of angiotensin converting enzyme 2 8 IECAS, ARB and / or NSAIDs) have a higher risk of poor disease progression (pneumonia, acute respiratory syndrome and cardiac involvement), mortality or hospital admission than patients not treated with these drugs. A retrospective study of all patients with confirmed SARS-CoV-2 virus infection in Alava is proposed. All patients with confirmed infection will be followed up from the first contact with the health system until its resolution (negative test) or death, if applicable. The data will precede the electronic medical history of each patient.",2020,-99,ASOCIACION INSTITUTO DE INVESTIGACION SANITARIA BIOARABA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Prophylactic use of treatments, +C10521,COV20_00532,Pre-clinical mouse models for the study of Covid19 and testing of therapeutic strategies,"The ultimate objective of this proposal is to develop a genetically modified mouse, susceptible to being infected by the SARS-CoVi-2 virus. We propose two models. The first consists of a knockin model in which the murine Ace2 gene is replaced by the coding sequence of its human counterpart. We know that Ace2 knockout mice develop phenotypes that may not be rescued by the expression of the human protein. Therefore, and in parallel, we propose the generation of a transgenic model, by means of a BAC that contains all the regulatory sequences for the expression of the murine Ace2 gene, and in which the coding sequence of said gene is replaced by that of the human gene ( cDNA). In both models, concomitant with the expression of the human ACE2 protein, the fluorescent protein tdTomatoo will be expressed, in order to be able to easily detect and isolate cells susceptible to being infected by the SARS-CoVi-2 virus.",2020,-99,FUNDACIÇÿN DEL SECTOR PǸBLICO ESTATAL CENTRO NACIONAL DE INVESTIGACIONES ONCOLÇÿGICAS CARLOS III,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Disease models, +C10522,COV20_00542,"Infection, hospitalization, ICU admission and death due to SARS-CoV-2 in a population cohort","Objective: to estimate the effect of sociodemographic characteristics, chronic diseases and other conditions on risk in infection, hospitalization and severe forms of COVID-19. Methods: Based on healthcare and epidemiological surveillance databases, the population cohort covered by the Health Service (640,000 people) will be constructed. Two sub-cohorts will be defined for specific analyzes: institutionalized people (n = 6000) and health professionals (n = 12,000). The incidence rates of cases with clinical suspicion, of infection confirmed by PCR, of hospitalizations, of ICU admissions, of assisted ventilation and of mortality will be calculated. Lethality will also be calculated in confirmed cases and in hospitalized patients. The predictor variables to be evaluated are sex, age, chronic diseases, pregnancy, obesity, hypertension, smoking, functional capacity, socioeconomic level, number of cohabitants, minors at home and use of services. Antibody seroprevalence will be assessed in a sample of patients from the sentinel network and / or donors.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION SANITARIA DE NAVARRA,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping, +C10523,COV20_00580,Study of the SARS-CoV-2 viral load in the respiratory tract and blood as a factor associated with the prognosis of COVID-19 in adults,"The general objective is to analyze the influence of the SARS-CoV-2 viral load in the lower respiratory tract (sputum or invasive samples if its study is indicated), as well as in blood and feces as indicators of disseminated disease, as factors associated with development of pneumonia and the evolution of the disease, measured by the need for assisted ventilation and cure or death. Virological variables will be included in an analysis along with demographic variables, comorbidities, and clinical and radiological characteristics of pneumonia. Also, the sensitivity of SARS-CoV-2 RT-PCR in nasopharyngeal smears will be evaluated. sputum and viremia. Finally, the excretion and infectivity of the virus in feces will be determined after the patients are cured.",2020,-99,Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis, +C10524,COV20_00587,Preparation of maps of the danger of transmission of COVID19 in urban spaces aimed at the application of anti-propagation measures at a detailed scale,"The project aims to analyze what is the spatial transmission behavior of the Covid_19 virus in urban spaces, in order to know where the main sources of contagion are located, which of them are more virulent and evolve at a faster rate, with what factors urban areas are related, and what are the key areas of action through anti-contagion measures to stop the spread. We understand that the spatial monitoring of contagion at the urban micro-scale level is key to cutting the chain of virus transmission. The spatial scope of study is constituted by the urban spaces of the province of Malaga, including its capital, an urban area in which results are already being obtained.",2020,-99,UNIVERSIDAD DE MALAGA,,Viruses,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics, +C10525,COV20_00595,Characterization and management of Post Intensive Care Syndrome in COVID-19 patients,"Implementation of a combined monitoring system (technological solutions and face-to-face visits) in patients who have overcome a critical episode due to COVID-19 to characterize the Post-Intensive Care syndrome and detect early needs for specific treatment or physical and cognitive rehabilitation. The follow-up will be done in person upon discharge from the ICU and 12 months after discharge from the ICU, and through the use of mobile applications and phone calls per month, at 3 months and at 6 months after discharge from the ICU. A diagnostic tree will be developed to detect survivors of critical illness due to COVID-19 who present moderate-severe physical, cognitive and emotional alterations 3 months after discharge to the ICU. These patients will be offered an extraordinary face-to-face visit with a specialist at 6 months.",2020,-99,FUNDACIÇÿ PARC TAULÇ?,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Digital Health,,,Spain,Spain,Clinical characterisation and management,Post acute and long term health consequences, +C10526,COV20_00622,Genetic Determinants and Genomic Biomarkers of Risk in Patients With SARS-COV-2 Coronavirus Infection,"Objective: Search for genomic risk biomarkers that may predispose to more serious infection prognostic stratification and / or response genomic biomarkers in patients who have received treatment during infarction. A whole genome association study (GWAS) will be carried out in a sample of 7000 Spanish patients and a whole genome sequencing study in a group of selected patients (300), collected by a national and international consortium that includes more than 15 hospitals. , complemented by a high-level research group. Clinical data (signs, symptoms and findings) and personal and epidemiological history will be collected in a common database designed ad hoc for this project. Thus, we will find genetic / genomic determinants of risk and poor evolution that allow a better stratification of patients and the adaptation and optimization of therapeutic protocols.",2020,-99,Consorcio Centro de Investigación Biomédica en Red M.P. (CIBER),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management", +C10527,COV20_00634,"Prognostic variables, resources consumed and cost in primary care of patients with COVID-19","This project will be led by Dr. Rosa Magallón Boyata, Principal Investigator of the Consolidated Group of Research in Primary Care of the Government of Aragon. At the present time, COVID-19 has generated the greatest public health crisis, putting the health system at serious risk of collapse. Thus, in mid-March it was necessary to resort to the national state of emergency and impose a home confinement that will continue, at least, until mid-April, with great chances of an extension. During this time, health services have been completely overwhelmed. In this new situation, tents and pavilions are being set up to be able to attend the increasing number of patients with mild, moderate or severe symptoms of the disease, deriving resources from other healthcare levels. In addition, the prognosis, as well as the clinical presentation, is highly variable, with no empirical evidence to corroborate these differences. In this project we want to stratify the infected population that does not require hospital admission, its pro-disposing factors, comorbidity and frailty, as well as analyze the use of resources in PC in this pandemic in our country.",2020,-99,Instituto de Investigación Sanitaria de Aragón,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management | Health Systems Research,"Prognostic factors for disease severity | Supportive care, processes of care and management | Health financing", +C10528,COV20_00668,Characterization and therapeutic management of immune hyperactivation associated with mortality in COVID-19,"The clinical deterioration of the SARS-CoV-2 infection would be the result of a combination of direct cytopathic effects induced by the virus and the immunopathology induced by a cytokine release syndrome associated with the immune response against the virus. The experience that is being acquired in our centers indicates that in the most serious cases the clinical picture is mainly related to the activation of an exaggerated immune response and an uncontrolled inflammatory process, which leads to multi-organ failure that ends in death. A recent study of 150 confirmed cases of COVID-19 in Wuhan, has just identified elevated ferritin and IL-6 as the main predictors of mortality, confirming that the hyperinflammation caused by the response to SARS-CoV-2 would be the leading cause of death in COVID-19. Our project aims to carry out an exhaustive study of the patient's immune status: i) establishing early cytokine monitoring to guide the targeted and personalized use of biological drugs, in order to rescue patients with a worse evolution from probable death; ii) studying the immunological factors associated with relative risk, progression and also with the development of immunity against the virus.",2020,-99,FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL GREGORIO MARAÑÓN,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management", +C10529,COV20_00675,Registry of SARS-CoV-2 infection in patients with hemoglobinopathies and / or splenectomies: epidemiological surveillance and study of morbidity and mortality in risk groups,"The SARS-CoV-2 infection registry in pediatric patients with clinically serious hemoglobinopathies, such as sickle cell disease (SCD) or Thalassemia major (TM), among others, and / or splenectomized patients aims to collect relevant epidemiological information for the surveillance of this risk group; It is intended to study the morbidity and mortality in this population in addition to the quantification of the resources used by this population during the current epidemic situation (hospitalization rate, treatments used, admission rate to intensive care units, among other markers). of an observational, descriptive, multicenter and ambispective study. With this study we want to study the socioeconomic impact and epidemiology of the COVID-19 disease in this population group.",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL GREGORIO MARAÑON,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping, +C10530,COV20_00698,Creation of the Cohort of COVID19 patients and samples associated with the Biobank of the Instituto de Investigación Sanitaria Galicia Sur (IISGS),"The creation of the cohort of COVID19 patients and samples associated with the IISGS Biobank in the health area of Vigo is the basis for the study of the COVID19 disease in a standardized and quality way. It will allow the execution of clinical and experimental studies to increase our knowledge and optimize the prevention, diagnosis, clinical follow-up and treatment of patients infected by SARS-COV-2 at a local and global level, favoring consortia and study groups with other national centers and international organizations for the development of joint research projects. To this end, a Coordination Unit of the COVID19-IISGS Cohort and a Scientific-Technical Committee have been created for the evaluation of research projects that require the use of data and samples from the cohort once they have the approval of the Relevant Ethics Committees.",2020,-99,FUNDACIÓN BIOMÉDICA GALICIA SUR,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Data Management and Data Sharing,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management | Research to inform ethical issues,Clinical trials for disease management | Research to inform ethical issues in Research, +C10531,COV20_00808,Clinical and immunovirological aspects of SARS-CoV2 infection in a cohort of pregnant women and newborns.,"National prospective multicenter study carried out in RECLIP healthcare centers. At least 150 mother-newborn pairs with confirmed SARS-CoV2 infection during pregnancy will be analyzed. Epidemiological and clinical aspects, treatment of the infection, evolution will be collected. In 50 couples, microbiological studies of SARS-Cov-2 will be carried out in respiratory, blood, placenta, urine and feces of the newborn, breast milk, and immunological samples at the time of diagnosis of the pregnant woman and at birth in the newborn , and prospectively up to 6 months of life of the infant, aimed at knowing in depth the transmission of the infection as well as the immune response that occurs in these populations against SARS-CoV-2",2020,-99,FUNDACION INVESTIGACION BIOMEDICA HOSPITAL GREGORIO MARAÑON,,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics, +C10532,COV20_00852,Incidence and characterization of profiles of low / high risk of complications in people> 60 years with COVID19.,"Population-based cohort study, with a 4-month retrospective-prospective follow-up (03/01/2020-30/06/2020), which will include 48,000 people> 60 years of age from Tarragona (1,500 of them institutionalized). Objectives: (i) to know the real incidence of COVID-19 infection, discriminating according to ""confirmed"" (PCR +) and / or ""suspected"" cases (COVID19-like without PCR confirmation); (ii) identify the frequency of presentation (initial and during evolution) of symptoms and signs of the disease in both types of patients (confirmed / suspected); (iii) characterize the clinical presentation profile (symptoms and signs) of COVID-19 infection in the population and explore prediction models for low / high risk of complication profiles (sudden worsening, need for hospitalization / ICU, death) based on possible predictor covariates (sex, age, symptoms / signs, comorbidity and previous medication).",2020,-99,IDIAP JORDI GOL,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis, +C10533,COV20_00901,Dual Vaccinia MVA virus for immunization against SARS-CoV-2,"For greater effectiveness and potency, an ideal vaccine should induce both humoral and cellular memory responses. We have developed methodology to obtain recombinant MVA vaccinia viruses that simultaneously express two antigens from two separate loci of the genome, without inactivating any gene in the genome. virus that can attenuate the response. In the case of Covid-19, it seems likely that protein S induces good neutralizing antibodies but a poor cellular response (1), so we propose to generate vaccine candidates that enhance the response of T cells by expressing, in addition to the SARS-CoV-2 glycoprotein S, the ns1 / 2 or N proteins. Vaccine candidates must be capable of inducing humoral immunity in addition to cellular immunity against conserved epitopes on intracellular proteins. Once the recombinant viruses have been generated, their immunogenicity will be evaluated in mouse models.",2020,-99,"INSTITUTO NACIONAL DE INVESTIGACION Y TECNOLOGIA AGRARIA Y ALIMENTARIA, O.A",,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies", +C10534,COV20_00923,Seroprevalence against SARS-CoV-2 in pregnant women and newborns,"Cohort study including 1000 pregnant women and their 1000 newborns in the community of Cantabria, which will be followed for one year. IgG and IgM anti-SARS-CoV-2 determinations will be made in the mother at the first pregnancy visit, on the day of delivery and at 6 and 12 months after delivery; in the newborn on the day of birth and at 6 and 12 months. Sociodemographic information and the process of care for pregnancy and childbirth will be collected. At follow-up, the newborn's somatometry and psychomotor development will be evaluated.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION MARQUES DE VALDECILLA (IDIVAL),,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease susceptibility, +C10535,COV20_00943,Immunological and virological factors in COVID-19 and their correlation with the evolution to severe forms of the disease.,"Prospective study to be carried out at the Son Espases and Son LLátzer Hospitals in Palma de Mallorca, the objective of which is to identify virological and immunological factors, as well as clinical, radiological and analytical factors, related to severe forms of COVID-19. During the months of April and May 20120, 150 patients diagnosed with mild, severe and moderate COVID-19 will be recruited (50 patients in each group) and determinations will be made in peripheral blood of baseline levels and at 2 weeks of IL1, IL6, IL8, IL10, TNFa and IL2R, of lymphocyte subpopulations and complement study, as well as study of semiquantitative viral load in oropharynx and peripheral blood and production of Ab against SARS-COV-2. The relationship of these parameters with epidemiological, clinical and radiological variables of mild, severe and moderate COVID-2 will be analyzed.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION SANITARIA ILLES BALEARS,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10536,COV20_00948,EMCOVID-19: Multiple Sclerosis and COVID-19,"MS is an autoimmune disease and its interaction with COVID-19 infection has not yet been studied. This is important for several reasons. 1) COVID-19 infection could modify the evolution of MS 2) MS could alter the response to COVID-19. Nor has the evolution of the infection been studied according to the immunomodulatory treatment (TME) received and whether it alters the evolution of MS. In this we intend to study a) how the infection by SARS-COV-2 affects the clinical and immunological status of patients with MS based on the characteristics of their MS and the MSD they take, b) how MS and MSD treatment influence in the appearance and development of the SARS-COV-2 infection and c) if there are beneficial effects of some MSDs in the evolution of the SARS-COV-2 infection or if some drugs used in the treatment of the infection could be beneficial for treating MS.",2020,-99,INSTITUTO INV. BIOMEDICA DE LLEIDA. FUNDACION DR. PIFARRE (IRBLLEIDA),,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10537,COV20_01100,CoviNanoVax: Design of a polymeric nanoparticle-based mRNA vaccine targeting dendritic cells,"CoviNanoVax arose from our previous experience in the development of polymeric nanosystems loaded with genetic material selectively targeting dendritic cells (DCs). These nanosystems will be used here as vaccines for the prevention of CoVid19. A coding mRNA for the antigenic proteins of the SARS-CoV-2 nucleocapsid will be encapsulated so that, once the nanoparticles have been injected into a healthy patient, they selectively target the DCs and transfect them. As it is an mRNA that encodes only antigenic proteins, and taking into account that the reverse transcriptase will not be present, the safety of the vaccine will be very high and, at the same time, since the mRNA is a highly antigenic macromolecule, it will develop a specific immune response to immunize healthy but susceptible people and protect them against future SARS-CoV-2 infections.",2020,-99,UNIVERSIDAD RAMON LLULL,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Vaccines research, development and implementation",Pre-clinical studies, +C10538,COV20_01112,EPICOS- Clinical Trial for the Prevention of Coronavirus Infection in Healthcare,"Randomized clinical trial to evaluate the efficacy of the daily single tablet dose of Tenofovir (TDF) (245 mg) Emtricitabine (FTC) (200 mg), daily single tablet dose of Hydroxychloroquine (HC) (200 mg), and daily dose of TDF (245 mg) FTC (200 mg) plus CH (200 mg) or placebo, for 12 weeks in: (1) decreased incidence of symptomatic disease and 2) decreased clinical severity of coronavirus infection (COVID -19) in hospital health personnel aged 18 to 65 years exposed to coronavirus infection (COVID-19) in Spain.",2020,-99,"FUNDACIÇÿN ESTATAL, SALUD, INFANCIA Y BIENESTAR SOCIAL, F.S.P.",,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10539,COV20_01138,Registry of patients with inflammatory and autoimmune diseases with SARS-CoV2 infection,"The project tries to generate a registry of all patients diagnosed with SARS-CoV2 infection and previously diagnosed rheumatological disease. To do this, EHR data will be collected from SARS-CoV2 + patients and rheumatological diseases in relation to their underlying disease, their previous treatment, the treatment that was being used when the symptoms of infection began, the course of the disease until its resolution, including the appearance of complications, the therapies used as treatment and the presence of risk factors. The objective is to subsequently analyze the data obtained in order to determine what is the influence of rheumatological diseases in the course of infection and if the therapies administered can be beneficial or harmful in terms of prophylaxis and / or less or greater severity of the disease. infection.",2020,-99,FUNDACION INSTITUTO DE INVESTIGACION MARQUES DE VALDECILLA (IDIVAL),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation | Health Systems Research","Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management | Prophylactic use of treatments | Health information systems", +C10540,COV20_00052,Identification of COVID-19 virus Mpro protease inhibitors by drug replenishment,"The project aims to discover inhibitors of the SARS-CoV-2 virus Mpro protease by reprovisioning drugs as new antiviral agents. For this, computer-aided drug design methods will be used. The process includes the preparation of the target structure by molecular dynamics, molecular screening using a molecular anchoring algorithm and the calculation of the free energy of binding of the best ligands. To carry out the virtual screening, databases of molecules approved as therapeutic agents and natural products will be used. The end result will be an affinity-ordered list of various molecules that can be tested in vitro.",2020,-99,Universidad Politecnica de Catalunya,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Pre-clinical studies, +C10541,COV20_00211,Study for the identification of cytokine profiles capable of predicting the development of respiratory distress secondary to infection by coronavirus 2 (SARS-CoV-2)),"We will carry out, for a week, daily blood draws from a cohort of 100 patients currently admitted to the HM Sanchinarro Hospital with a confirmed or highly suspected diagnosis of COVID-19. A broad panel of cytokines (LUMINEX) will be determined in these samples, prospectively correlating the analytical results with the development of severe SARS. Using computer algorithms, we will establish the determinations that best predict the appearance of this complication. The analysis will focus on proteins included in the portfolio of commercial companies that produce, on an industrial scale, diagnostic kits using ELISA. Thus, the markers found will be immediately available at any healthcare center in the country. In parallel, we will study the interindividual genetic variability and the evolution of the viral load in these cases. In a second phase we will develop more precise and patentable multiplex kits.",2020,-99,FUNDACION DE INVESTIGACION HM HOSPITALES,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C10542,COV20_00491,Evolution of the inflammatory profile and redox status in COVID-19 patients: Possible therapeutic targets?,"The risk of patients with COVID19 increases with age, as does the redox status and the inflammatory component. In relation to the hypothesis of this work is that in COVID19 patients there is an inflammatory profile associated with the severity of the disease that evolves depending on the ability of the patient to stabilize its redox status. The objectives of this work are to carry out a clinical biological and molecular characterization of the Covid19 disease as well as to establish one of innovative therapeutic targets and prognostic biomarkers of clinical activity and even death that can considerably reduce the mortality trend that our country currently suffers.",2020,-99,Hospital Clínico Universitario de Valladolid,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Innovation,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies, +C10543,COV20_00508,ASSESSMENT OF THE SPECIFIC IMMUNE RESPONSE TO SARS-CoV-2,"The control of SARS-CoV-2 infection is based on the development of an effective immune response against the virus and on the appearance and maintenance of memory T lymphocytes that can be activated if the virus reappears. The generation of memory T lymphocytes is also necessary to ensure the efficacy of vaccination strategies. Using cellular techniques (ELISPOT, flow cytometry) we will study the characteristics of the immune response in patients who have resolved the infection, regardless of its clinical manifestations. In addition, we will analyze the evolution of the infection and the immune response in patients with chronic inflammatory diseases to study whether the immunosuppressive treatments (biological or pharmacological) could have had any positive or negative impact on the course of the infection and on the establishment of immunological memory.",2020,-99,Fundacio Institut del Mar dÇîInvestigacions Mediques,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management", +C10544,COV20_00652,Determinants of resistance and pathogenicity in SARS-CoV-2 infection: genomic and biochemical mechanisms,"The clinical management of COVID-19 patients and the implementation of measures to prevent, alleviate and eventually eradicate the disease will require not only a complete characterization of the structural and biological features of the virus, but also a deep understanding of the molecular intricacies of the virus-host cell interaction. In this project we will carry out comparative studies aimed at identifying viral and host genomic features involved in pathogenicity and disease susceptibility. We will also study the role of cellular proteases involved in SARS-CoV-2 infection and explore their regulatory mechanisms, their endogenous inhibitors and their potential role in aging-associated disease vulnerability. These studies will be complemented with a CRISPR / Cas9-based screening designed to search for new cellular factors involved in the infection process and host response.",2020,-99,Universidad de Oviedo,,Viruses | Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis", +C10545,COV20_00067,Evaluation of epidemiological scenarios of the COVID19 disease using an original model using membrane computing,"The aim is to apply our already recognized knowledge in the establishment of computational models based on new membrane computing techniques in order to develop a multiparametric and multi-hierarchical model for predicting the effect of interventions in the Co Vid 19 epidemic. The model allows enter ranges of values at multiple levels (for example, ages, contact rates, contact times, transmission rates, protective transmission measures, effects of possible therapeutic and vaccine agents - see below for other possible changes) and observe how the Modification of each of the factors or of several of them simultaneously influences the epidemiological trend of the disease. The purpose is to help decision-making for the establishment of on-demand interventions for specific scenarios.",2020,-99,VHIR-HUVH (INSTITUTO DE INVESTIGACION HOSPITAL UNIVERSITARI VALL D'HEBRON),,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Impact/ effectiveness of control measures, +C10546,COV20_00115,Real-time quantification of new unreported cases of COVID-19 in Spain,"The proposed project aims to develop a set of mathematical models that make it possible to quantify in real time the new unreported cases of COVID-19 in Spain, by autonomous communities or by other areas of interest. The estimates provided by these models will be used to study the dynamics of the disease based on the application of compartmental epidemiological models (type SIR, SEIR, SIRS, etc.) that will allow a more precise estimate of the associated mortality and morbidity. . Similarly, these estimates will be used to carry out an exhaustive cost-effectiveness analysis in different realistic action scenarios, both from the point of view of public and social management, which may help decision-making in the field of national public health system and also within each Spanish autonomous community, in order to face the present pandemic and in similar future situations.",2020,-99,Centre de Recerca Matemàtica (CRM),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping, +C10547,COV20_00207,Study of the immune response in nested cases in a cohort to evaluate the effect of antiretrovirals on the evolution of the SARS-COV-2 coronavirus infection.,"Patients infected with the CoVid-19 virus are characterized by a high degree of inflammation and dysregulation of the specific T response. In studies carried out with patients from the Hospital Universitario La Paz with respiratory diseases, we have found that the hypoxia and oxidative stress suffered by these patients cause the inflammasome complex to be activated. This complex also has effects on pyroptosis and on the production of type I IFNs. On the other hand, the inflammatory condition of the patient will directly condition the specific T response. In short, understanding the inflammatory state in patients provides relevant information on the evolution of the pathology. The aim of this project is to study the effect of the drugs included in this clinical trial in patients with CoVid-19, on the activation of the inflammasome and its effect on inflammation and the T response. These data associated with the evolution of the patient are determinants to classify responding patients and mechanisms of viral evasion.",2020,-99,Fundación para la Investigación Biomédica del Hospital Universitario La Paz,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Clinical trial (unspecified trial phase), +C10548,COV20_00210,Determination of the presence of SARS-CoV-2 in environmental samples and its potential indirect transmission.,"Although SARS-CoV-2 and other coronaviruses are transmitted mainly directly between individuals during epidemic phases, the permanence of the virus in the environment has the potential to cause new outbreaks despite the mitigation efforts deployed. SARS-CoV -1 was detected in hospital wastewater in China and it was shown that viral particles could remain infective long enough to constitute a risk. We will investigate the potential for environmental transmission of the virus in the specific conditions of our country. primarily in the analysis of sewage treatment plants and in the release of the virus through the intestine. We will also study the stability of the virus, as well as its presence in other environments, such as common surfaces such as plastics, stainless steel or glass. This will provide valuable information for managing the epidemic.",2020,-99,Universitat de València,,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics, +C10549,COV20_00278,ACE2-ORG. Development of a human cellular platform unveiling Angiotensin-converting enzyme 2 (ACE2) - sars-CoV-2 interactions,"There are no models allowing to unveil the molecular pathways and cellular responses differently regulated upon SARS-CoV-2 infection in human tissues. Organoid technology represents and affordable solution to COVID-19 research. Our consortia is able to infect a plethora of human organoids opening the door for drug screening for COVID19 treatment. These results are part of a present manuscript under review in Cell. Bases in our current finding our aim is to understand, identify and target ACE2-SARS. COV2 cellular responses exploiting kidney and heart organoids exposed to systemic conditions worsening COVID19 disease (e.e. Diabetes). Using scRNA sequentiation we will unveil unique and common cellular responses upon SARS-coV-2 infection and use primary cell cultures and retrospective COVID19 necropsies for validation. This approach will identify top ranked pathwys differentially regulated upong SARS-CoV.2 infection in control and diabetic backgrounds.",2020,-99,Instituto de Bioingeniería de Cataluña,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis", +C10550,COV20_00349,Exploiting protective immune responses to COVID-19 to unravel mechanisms associated with favorable clinical outcomes (PROTECTIVE STUDY),"Because COVID19 spectrum of disease range from asymptomatic disease to severe lung injury leading to death, we aim to exploit extreme clinical phenotypes of COVID-19 disease to identify mechanisms that can be leveraged to improve outcomes and to identify predictors of adverse outcomes. Because the clear correlation between clinical outcomes and age, we plan to recruit individuals across a broad range of age, including pediatric populations, reflecting the broad range of COVID19 disease severity. We will interrogate targeted biological pathways (i.e., ACE2 expression and polymorphisms, antiviral responses and innate and adaptive immunity) and untargeted pathways using plasma metabolomics and enzymolomics. These parameters will be correlated with the clinical phenotype and with virologic measures of CoVID19 using multiparametric data integration through a bioinformatic approach.",2020,-99,FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL RAMÓN Y CAJAL,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10551,COV20_00373,"SARS-CoV-2 Inhibition, Host Selection and Next-Move Prediction Through High-Performance Computing.","We will fight SARS-CoV2 by using massive high-performance computing. Thanks to the recently published X-Ray structures, we will unveil the physico-chemical properties of the viral spike protein, those of the human ACE2 receptor and those of the complex they form to permit virus to infect cells and spread. This information, well implemented with knowledge-based bioinformatics techniques, will help us to understand the mechanism of viral entrance into the cell and what are the ""next evolutionary moves"" of the CoV family. Unbiased tajectories along with extensive free-energy calculation would help to identify new ""druggable spots"" (not detectable by crystallography). On this knowledge, we will start a drug discovery effort (of commercially available drugs first) to inhibit the interaction between the virus and the human host, hence impeding virus internalization and spread.",2020,-99,Fundació lnstitut de Recerca Biomédica (IRB Barcelo1,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C10552,COV20_00416,"COVID-19, IMMUNE RISK PROFILE","At present, it is not known whether the minority of COVID-19 cases that evolve poorly are due to an excess or a defect of the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological / virological scenarios in which this infection develops. Objective: To generate algorithms / indices to stratify patients by immunological / virological risk profile applicable to the analysis of clinical trials with ongoing or future immunomodulars. Methods: 1) Capture and daily analysis of inflammation, coagulation, immunology and microbiology parameters as well as general analysis in relation to the origins of the samples, demographic data and clinical evolution; 2) Measurement in 120 patients of the level of 16 cytokines and 32 lymphocyte populations for: 3) the generation of prognostic and therapeutic orientation algorithms from 2; 4) Detailed identification through Nanostring® transcriptomics of the activated immune response pathways in 40 patients and thus confirm / improve the algorithm generated in 3. Support modules: 5) sample collections, 6) extraction of clinical data, 7) Bioinformatic analysis and biostatistics and 8) Communication / dissemination.",2020,-99,VHIR-HUVH (INSTITUTO DE INVESTIGACION HOSPITAL UNIVERSITARI VALL D'HEBRON),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10553,COV20_00437,Decoy-ACE2: Use of catalytically inactivated soluble ACE2 as anti CoVid19 drug,"2,3]). We will purify wild type or mutant ACE2 by affinity chromatography exploiting an artificial removable tag. We will prove that the mutant forms of ACE2 are catalytically inactive, stable, and that they bind to the binding region of the viral protein S. We will evaluate in cell cultures (collaboration with Jesús Rodríguez Díaz, Dept of Microbiology, Hospital Clínico-Universidad de Valencia) the potency of the mutated forms to inhibit the infection of viral inoculums. We will determine (crystallography or cryoEM) structures of mutant ACE / S binding domain complexes.",2020,-99,Consorcio Centro de Investigación Biomédica en Red M.P. (CIBER),,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies", +C10554,COV20_00571,Deciphering ACE-2-Mediated SARS-COV-2 Lung Infection,"Difficulty breathing due to severe pneumonia is by far, the most life-threatening emergency symptom reported for COVID-19. This is because the SARS-CoV-2 virus accesses host cells via the enzyme ACE2, which is most abundant in the alveolar cells of the lungs. We aim to study SARS-CoV-2 receptor ACE2 to identify the regions / residues critical for an efficient cell entry. We also aim to determine how the genetic variants / polymorphisms of main ACE2 receptor found in Spanish population and different tissues impinge on SARS-CoV-2 infection capacity. This have a clear therapeutic applications (eg development of ACE2 peptide comprising the critical region as a viral attachment inhibitor and prospective antibody generation) and can be easily transferred to the clinic as it cold explain why different patients have a different susceptibility, symptoms, and outcome of COVID19 depending on the ACE2 polymorphisms. Finaly in an unprecedented analysis of the COVID19 desease in human lung epitheliym, we will make use of CRISPR / Cas9 to study how ACE2-CoV-2 infection affects epithelial organization, cells most susceptible to infection and we will confirm the previous finding in a totally translational / bench-to-bedside approach.",2020,-99,Fundación Instituto de Investigación Sanitaria Illes Balears,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis", +C10555,COV20_00617,Dynamic prediction of scenarios of COVID-19 impact in the short and medium term (PREDICO),"It is about predicting the evolution of the expansion and incidence of COVID-19, solving the main problems that known models are facing: the disputed reliability of the available data, both due to difficulties in the detection mechanisms and due to a probable abundance of asymptomatic infected. For this, a work is proposed on three fronts: a) based on compartmental models, which provide systems of differential equations; b) with the so-called Empirical Dynamic Modeling, which dispenses with equations, thus eliminating any dependence on the fact of predetermining causal agents; and c) through an analysis of the analysis of the Spanish social network, which will feed back a) and b). The works in these three blocks will have continuous interconnection.",2020,-99,Universidade de Santiago de Compostela (USC),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease surveillance & mapping, +C10556,COV20_00654,"COVID-19, immunological risk profile (attached to the project presented by the VHIR IP R Pujol-Borrell)","At present, it is not known whether the minority of COVID-19 cases that evolve poorly are due to an excess or a defect in the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological scenarios in which this infection develops. Objective: To generate algorithms to stratify patients by immunological risk profile applicable to the analysis of clinical trials with ongoing or future immunomodulars and, specifically, to support therapeutic strategies. Modules 1) daily collection and analysis of inflammation, coagulation, immunology and microbiology parameters as well as biochemistry in relation to the origins of the samples and the demographic data of the patients, evolutionary follow-up and progressive assessment of the most predictive indices; 2) Measurement of the level of 18 cytokines and 32 lymphocyte populations in 120 patients; 3) Generation of prognostic and therapeutic orientation algorithm; 4) Identification of the activated response pathways. Support modules include generating sample collections, clinical data extraction, and statistical analysis.",2020,-99,Instituto de Investigación Biomédica de Bellvitge (IDIBELL),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10557,COV20_00660,Identification and Characterization of the Protective T Immune Response Against SARS-CoV-2: Successfully Guiding Vaccine Design,"At present we do not know if the SARS-CoV-2 infection will be able to generate immunological memory at the population level. The presence of immunological memory T is essential for the control of a new CoV-2 epidemic outbreak. Under these premises, this project proposes: 1) Identify the CoV-2 regions recognized by the immune T response associated with protection. 2) Determine the generation time of these responses. 3) Characterize the functionality of the T responses associated with protection against CoV-2. This information is essential to successfully design and evaluate the immunogenicity of a new prototype T vaccine in a second phase. The ultimate goal is to achieve prolonged population protection against SARS-CoV-2 through vaccination.",2020,-99,INSTITUTO DE INVESTIGACIÇÿN DEL SIDA IRSICAIXA,,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10558,COV20_00711,MIND/COVID-19: Mental health Impact and NeeDs associated with COVID-19: a comprehensive national evaluation in Spain.,"A prospective cohort study of three groups: (1) COVID-19 cases or close contacts recently isolated or quarantined; (2) healthcare workers; and (3) the general population, including both adults and children / adolescents. Recruitment through epidemiologic surveillance services, hospitals, primary care centers in 6 Spanish Autonomous Communities (groups 1 & 2), a panel survey (group 3 - adults), and snowball sampling through social media (group 3 - children / adolescents). Web-based surveys at baseline and 6-month follow-up assess: current living and employment status; COVID-19 infection status; mental health (post-traumatic stress, panic, depression, anxiety, alcohol use, suicidality; services use); psychological functioning; health and quality of life. Specific modules focus on impact of isolation or quarantine (group 1) and care for COVID-19 patients (group 2). Children / adolescents receive adapted modules. Smartphone-based daily brief surveys among groups 1 & 2 will provide additional assessment of main outcomes in the two weeks following baseline assessment.",2020,-99,Fundació Institut del Mar d'investigacions Mèdiques,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts, +C10559,COV20_00736,"Study of the dynamics of the SARS-CoV-2 epidemic with physico-mathematical epidemiological models. Monitoring, control strategies, simulations and surveys","An investigation initiated on the growth dynamics of the SARS-CoV-2 epidemic will continue using physico-mathematical epidemiological models. The study will be carried out on the official data on the number of patients. The following will be investigated: the phases of the epidemic (exponential growth, peak and decrease); gravity according to the height and width of the peak; growth rate and reproductive number; effect of uncertainty on the number of infected. The scientific basis for the design of the most suitable containment strategies will be proposed according to the optimization of parameters (not only confinement). Simulations will be carried out in different scenarios of the incidence and affected curves, which help to anticipate control measures, and to understand the risk of importation of cases and outbreaks.",2020,-99,Universidad de Murcia,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics, +C10560,COV20_00750,Radiographic Chest Inspection Screening in COVID19 Patients,"One of the symptomatic aspects of COVID19 is the effect of pneumonia. Our group is an expert in image analysis and its treatment for combined use with radiologists. With the resources we have, we want to help develop a radiological screening system based on artificial intelligence. to help identify the severity of the pathology. During the project, the exploration capacity of the solution will be addressed, looking for leading companies in the sector such as engines and image acquisition assistance.",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas.,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Innovation,,,Spain,Spain,Clinical characterisation and management,"Supportive care, processes of care and management", +C10561,COV20_00755,Short and Medium Term Therapies for the Treatment of COVID-19: Senolytics and Vaccine Development,"According to the WHO, hypertension, cardiovascular and chronic respiratory diseases, diabetes, immunosuppression, cancer, along with old age, belong to the specific risk group of people affected by the current COVID-19 pandemic. As we age, our body accumulates senescent cells, which produce harmful effects in the body, and are known to play a causal role in the appearance of the diseases indicated above. This fact, together with data that is becoming known, place senescent cells as targets to eliminate or alleviate the symptoms of infection. The main objective of this project is the specific elimination of senescent cells through the use of senolytics, in order to improve the clinical picture of those affected. The fact that some senolytics are already in the clinical phase, means that its use in patients would be faster. The development of vaccines based on cellular response is also raised here.",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase), +C10562,COV20_00788,Mechanistic model based on artificial intelligence for the reuse of drugs against SARS-CoV-2 infection,"The rapid spread of SARS-CoV-2, a new virus, has gripped healthcare systems without adequate therapies. Although the development of a new drug is not feasible in the short term, the solution of reusing drugs with other indications would bring the availability of new therapies closer. Computational approaches have proven to be faster and cheaper than experimental ones. Among these, those based on mechanistic models, which allow inferring cause-effect relationships, have shown greater effectiveness than traditional solutions such as virtual screening or others. We propose the use of a mechanistic model based on artificial intelligence that has already demonstrated its effectiveness in rare diseases for the reuse of drugs for Covid-19.",2020,-99,Fundación Pública Andaluza Progreso y Salud,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10563,COV20_00792,Clinical utility of the analysis of IL-6 signaling as an indicator of COVID-19 disease activity. Therapeutic opportunity with IL-6 trans-signaling blockers,"1) Analysis of the inflammatory response by means of serum cytokines profile related to IL-6 signaling to stratify patients, assess COVID-19 disease activity and select patients to attenuate the inflammatory response by blocking IL-6. 2) Analysis of SNPs of the genes that participate in IL-6 signaling that can explain exacerbated reactions (bioinformatics data and data to be obtained with our samples). 3) To demonstrate the importance of a selective blockade of IL-6, that is to say to block only the transsignaling of IL-6 in patients where there is a severe inflammatory response with high levels of soluble IL-6 receptor. (sIL-6R) and low sgp130 (natural trans-signaling buffer), does not affect the classic IL-6. This contrasts with the use of Tociluzimab, where all IL-6 responses are inhibited, affecting the classic regenerative and defense IL-6 signaling in inflammation processes.",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas.,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis, +C10564,COV20_00932,Regulation of macrophage extravasation by α2 adrenergic agonists in CTS associated with COVID-19,"Patients with severe COVID-19 develop cytokine storm syndrome (CTS) that seriously worsens their prognosis. CTS is characterized by an excessive accumulation of activated macrophages that cause a massive release of pro-inflammatory cytokines. Macrophage depletion in the development of STC has been reported to decrease lethality in several animal models. Data from our laboratory demonstrate that α2 adrenergic receptor agonists prevent the accumulation of neutrophils in the inflammatory focus and preliminary results have shown a similar anti-inflammatory effect in circulating monocytes. The main objective of this project is to generate the mechanistic rationality that allows supporting α2 adrenergic agonists as modulators of the migration of monicycles to the inflammatory focus, in order to prevent / treat COVID-19 patients who develop CTS.",2020,-99,Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC),,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Immunity, +C10565,COV20_00935,Medium and long-term forecast of the spread of COVID-19,"This project seeks to evaluate, through simulation, of: (1) analyzing the effect of the spread of new epidemics on a European scale as well as the effectiveness of policies to restrict the movement of individuals: (2) the impact of climatic conditions (both summer and winter) in the spread of the epidemic: (3) the effect of a potential selective vaccination of the population taking into account different levels of vaccine efficacy as well as potential mutations in the virus that reduce the immunity of the group who has already been vaccinated or has suffered from the disease; (4) the efficiency of different social distancing measures (school closings, job closures or remote work for a percentage of the working class, social isolation, etc.) on the following stages of infection, taking into account different possible levels of collective immunization .",2020,-99,Universidad Carlos III de Madrid,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C10566,COV20_00944,MULTICENTRIC OBSERVATIONAL REGISTRY OF PATIENTS WITH SARS-COV2 INFECTION IN SPANISH PICU (SECIP-COVID),"Multicenter prospective observational study to characterize SARS-VOC infection in critically ill pediatric patients. It is an online registry using an electronic form in which pediatric ICUs from all over Spain will participate. The registry is promoted and sponsored by the Spanish Society of Pediatric Intensive Care. Demographic, clinical, epidemiological, diagnostic, therapeutic, microbiological, and prognostic variables will be recorded.",2020,-99,FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL GREGORIO MARAÑÓN,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Data Management and Data Sharing,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis, +C10567,COV20_00968,Levels of naïve T lymphocytes as a predictor of the efficacy of the immune response against SARS-CoV-2 and its potential vaccines,"The effective immune response capacity against a new pathogen will depend primarily on the specific recognition capacity of native T lymphocytes. The reduction of these cells as a consequence of physiological aging or secondary to pathology could be responsible for the inadequate control of the infection against SARS-COV-2. In patients with a certain genetic or physiopathogenic component, an exaggerated and uncontrolled inflammatory response may occur, perhaps as a compensatory mechanism, which together with other risk factors leads to a fatal outcome. Defining the lymphocyte profile that characterizes patients with different degrees of SARS-CoV-2 involvement will make it possible to predict those with a higher risk of complications or who might not benefit from vaccination once it is available.",2020,-99,Fundación para la Investigación e Innovación Biosanitaria en Asturias - FINBA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis, +C10568,COV20_00988,Impact of the COVID-19 pandemic on the mental health of workers in medical devices. International multicenter study: the COVID-19 HEROES study,"Although outbreaks of previous infectious diseases such as SARS have generated mental health problems in affected communities, the health emergency caused by SARS-CoV-2 is reaching an unprecedented impact, bringing health systems like Spain closer to collapse. Data from China highlights the importance and urgency of examining the psychosocial impact of COVID-19. This urgency is even greater in the case of people with a higher level of risk, among whom are workers of medical devices. Given the magnitude of this public health problem and the exposure to the pandemic and its derivatives suffered by health care device workers, this prospective, multicenter, 12-month follow-up cohort study identifies stressors and protective factors, in order to to inform health policies immediately.",2020,-99,FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL UNIVERSITARIO LA PAZ,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C10569,COV20_01007,Disruption of viral transport processes mediated by microtubules,"SARS-CoV-2 depend on microtubules for its internalization and release process, therefore microtubules can constitute an effective target to stop its replication. since they are involved in important cellular processes essential for growth and proliferation, essential for viral replication. Tools are available to visualize the movement of microtubule transporters attached to viral model peptides and thus evaluate their response to miniscule concentrations of drugs as well as the world's largest library of drugs directed against tubulin. The library will be screened in the evaluation system developed looking for drugs that inhibit this transport and viral replication at tolerable doses.",2020,-99,AGENCIA ESTATAL CSIC CENTRO DE INVESTIGACIONES BIOLÇÿGICAS,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C10570,COV20_01031,Determination of predictive phenotypes of complications in COVID-19 and evaluation of the efficacy of immunosuppressive treatments,"The objective of the project is (1) to identify predictive phenotypes of need for mechanical ventilation in the initial evaluation of patients and their evolution in the first days of admission, and (2) to evaluate the efficacy and safety of immunosuppressive treatments used in patients without Mechanical ventilation with elevation of macrophage activation syndrome markers. They will be carried out through multicenter retrospective cohort studies, with advanced statistical analysis for observational studies.",2020,-99,Fundación Publica Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI) Hospital Universitario Virgen Macarena,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Clinical trial (unspecified trial phase)", +C10571,COV20_01046,Safety of breastfeeding (BF) in confirmed SARS-COV-2 (COVID-19) infection,"Currently there are no formal studies on the efficacy of BF in the transfer of protective factors against SARS_COV-2, and its safety, understood as the exclusion of it as a source of spread of the virus and cause of illness in infants. BF is essential for the correct development of the most vulnerable neonatal populations. This cohort study will evaluate whether there is transmission of the virus through BF (using highly sensitive technology) and whether it depends on viral load. In addition, it will investigate the transfer of immunological / inflammatory factors and microbiological markers potentially associated with the severity of Covid-19",2020,-99,FUNDACION PARA LA INVESTIGACIÇÿN BIOMEDICA DEL HOSPITAL UNIVERSITARIO LA PAZ,,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis", +C10572,COV20_01209,Changes in lung function tests in patients with CoVid19 pneumonia,"The project consists of a prospective, observational, multicenter study that will evaluate the changes in lung function (forced spirometry, measurement of static lung volumes using plethysmography and carbon monoxide pulmonary diffusion test) that patients admitted with pneumonia will present. by CoVid19 according to the level of severity at 4 and 26 weeks after hospital discharge. Restrictive pulmonary alterations will be confirmed by imaging tests (high resolution chest CT). The presence of immune response phenomena that lead to pulmonary fibrosis will be related to demographic and clinical variables and a series of biological markers, some of them already described as co-participants in the pathogenesis of pulmonary interstitial diseases, specifically of the idiopathic pulmonary fibrosis.",2020,-99,FUNDACION HOSPITAL CLINICO UNIVERSITARIO DE VALENCIA,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences, +C10573,COV20_01213,Mathematical modeling and prediction of the incidence of COVID-19 outbreaks in Europe,"We will develop a series of mathematical models that describe the current COVID19 coronavirus epidemic, with various levels of sophistication SIR, SEIR, SSEEIIR, with various delays and infectious structures adapted to the updated medical literature as medical studies specify the parameters of the local situation. . The adjustment method of the various parameters will be carried out using linear regression (normal equation) and machine learning (gradient descent). We will consider the impact of social distancing imposed in various states, as well as other control strategies, in order to measure its effectiveness and determine the best measures to prevent future outbreaks of COVID in the future.",2020,-99,Universidad del País Vasco/Euskal Herriko Unibertsitatea,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C10574,COV20_01304,Th1 / Th2 / Th17 / Treg response and TLRs / KIR receptors in clinical evolution of COVID19,"The immune response is crucial in patients from day 5-7 of symptom evolution. At that time, certain patients unleash an exaggerated immune response that aggravates their clinical situation (cytokine storm), while others progress without known cause. Being able to analyze the Th1, Th2, Treg and Th17 response in these patients upon admission could have a predictive value of later severity of the disease. An exacerbated activation of the Th1 response and low Th2 could produce that described cytokine storm. The Treg and Th17 response could also modulate this response. In parallel, the initial control of SARS-CoV-2 infection is also limited by the expression of Toll-like receptors (TLRs) expressed on monocytes and dendritic cells (TLR-7 and TLR-8). Also, the KIR receptors on NK cells are important for the clearance of viral infections.",2020,-99,Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal (FIBIO),,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C10575,COV20_01333,Inborn errors of Immunity and predisposition to infection by SARS-Cov-2 and the severity of COVID-19. International coordinated action. Full exomic sequencing. (project 1),"SARS-Cov-2 infection is mild or even asymptomatic in many patients, but it can cause severe illness (COVID-19), mainly in patients older than 50 years, especially those with comorbidities. There are, however, young patients without risk factors with severe forms of the disease. Some of these patients may have inborn errors of immunity (diseases often with incomplete penetrance). The main objective is the sequencing of the complete exome, using massive sequencing techniques, in patients under 50 years of age in the Spanish territory without comorbidities or risk factors. The project is part of an international consortium, of which we are one of the participating groups (https://www.cvidhge.com), in which information will be shared to carry out population studies that allow progress towards precision medicine in patients with COVID-19.",2020,-99,FUNDACIÓN INVESTIGACIÓN BIOMÉDICA HOSPITAL LA PAZ,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C10576,COV20_01334,Inborn errors of Immunity and predisposition to infection by SARS-Cov-2 and the severity of COVID-19. International coordinated action. Full exomic sequencing. (project 2),"SARS-Cov-2 infection is mild or even asymptomatic in many patients, but it can cause severe illness (COVID-19), mainly in patients older than 50 years, especially those with comorbidities. There are, however, young patients without risk factors with severe forms of the disease. Some of these patients may have inborn errors of immunity (diseases often with incomplete penetrance). The main objective is the sequencing of the complete exome, using massive sequencing techniques, in patients under 50 years of age in the Spanish territory without comorbidities or risk factors. The project is part of an international consortium, of which we are one of the participating groups (https://www.cvidhge.com), in which information will be shared to carry out population studies that allow progress towards precision medicine in patients with COVID-19.",2020,-99,FUNDACION CANARIA INSTITUTO INFESTIGACIÇÿN SANITARIA DE CANARIAS (FIISC),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C10577,COV20_00388,"COVID-19, immunological risk profile (attached to the project presented by the VHIR IP R Pujol-Borrell)","At present, it is not known whether the minority of COVID-19 cases that evolve poorly are due to an excess or a defect in the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological scenarios in which this infection develops. Objective: To generate algorithms to stratify patients by immunological risk profile applicable to the analysis of clinical trials with ongoing or future immunomodulars and, specifically, to support therapeutic strategies. Modules 1) daily collection and analysis of inflammation, coagulation, immunology and microbiology parameters as well as biochemistry in relation to the origins of the samples and the demographic data of the patients, evolutionary follow-up and progressive assessment of the most predictive indices; 2) Measurement of the level of 18 cytokines and 32 lymphocyte populations in 120 patients; 3) Generation of prognostic and therapeutic orientation algorithm; 4) Identification of the activated response pathways. Support modules include generating sample collections, clinical data extraction, and statistical analysis.",2020,-99,IGTP (Instituto de Investigación Germans Trias i Pujol),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Disease pathogenesis | Supportive care, processes of care and management", +C10578,COV20_00702,Use of ozone for the reuse of personal protective equipment (PPE). Study O3CoVid19PPE.,"The fight that is currently being waged in Spain against CoVid19 has many fronts. One of the most important at a strategic level is the shortage of personal protective equipment (PPE), which has resulted in: 1) a high percentage of infected health professionals, 2) reduction in the number of operational professionals, 3) that the professionals can spread the infection. Ozone has been used for decades in the treatment and disinfection of water (waste and for public use) and air. At low concentrations it destroys most viruses in a few minutes. If this effect on CoVid19 is confirmed, ozone could be used to: 1) inactivate the virus in PPE and facilitate its rapid reuse and availability for professionals, 2) reduce the number of PPE removal procedures as a risk factor.",2020,-99,Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C10579,COV20_00749,Design and development of peptide inhibitors of SARS CoV2 virus entry for human use,"Herein we are proposing the use of a low throughput peptide-screening assay to identify peptides that can inhibit SARS-CoV2 virus entry. The rationale is logical, the technology developed to identify these peptides, the feasibility of using peptides inhibitors of viral entry has been tested and proven and the translation of such findings to the clinic (e.g. clinical trials) is practical. Hence, our group is well positioned to tackle the immediate and growing need to develop novel compounds that can treat patients infected with SARS-CoV2. As principal investigator, I have a proven track record in Virology, with a particular emphasis on viral entry and the development and/or identification of compounds that inhibit viral entry. Thus, the proposal outlined below is well within my and my laboratories expertise and capabilities.",2020,-99,"Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P.",,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C10580,COV20_00764,Structural and Dynamic Characteristics of Intrinsically Disordered Proteins of the SARS-CoV-2 Virus,"A significant proportion of the SARS-CoV-2 proteome lacks homology to known proteins and appears to have no defined structure. Intrinsically disordered proteins (IDPs) are essential for viral infections as they hijack human regulatory networks. IDPs are refractory to structural analysis by X-ray crystallography or cryoelectron microscopy. The objective of this project is to characterize the partial structure and dynamics of three disordered proteins and three peptides of the SARS-CoV-2 proteome, for example, the segment spanning residues 962-1021: FGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMEL TPWQ. We will use NMR spectroscopy and molecular dynamics, which are the only methods that provide information at the atomic level about PIDs.",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C10581,COV20_00856,Application of AI to the immediate prediction of time series to optimize resource management in epidemics,"Given the uncertainty generated by the health crisis, and from the large amount of data that is generated every day on the COVID19 disease, we propose to apply the most modern and reliable techniques for analysis and prediction of spatio-temporal series using / deep-learning / and others paradigms of artificial intelligence. The objective is to immediately develop predictive systems for infections, admissions, ICU patients and deaths by province and autonomous community, together with other magnitudes (logistical, economic, ...) that allow to guide more effectively the action of the Ministry of Health in this and other crises. In addition, a retrospective analysis is proposed that makes it possible to determine a posteriori the start date of each outbreak of the epidemic as well as visualization tools and dashboards that allow the extraction of useful knowledge and facilitate decision-making based on the data.",2020,-99,UNIVERSIDAD NACIONAL DE EDUCACIÇÿN A DISTANCIA -- UNED,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies | Clinical characterisation and management,"Disease surveillance & mapping | Supportive care, processes of care and management", +C10582,COV20_01054,STUDY OF CONTAMINATION OF SURFACES AND PERSONAL PROTECTIVE EQUIPMENT BY PATIENTS WITH SERIOUS RESPIRATORY INFECTION BY CORONAVIRUS 2 (SARS-CoV-2) OF TREATED SYMPTOMATIC PATIENTS WHO REQUIRE ADMISSION TO THE INTENSIVE MEDICINE SERVICE.,"The use of high-flow nasal cannulas (CNAF) in disease caused by SARS-CoV-2 (the causative agent of COVID-19) could be limited by the risk of generation of aerosols that have been associated with an increase in the risk of transmission of airborne pathogens. Our objective will be to determine the degree of contamination of the surfaces and personal protective equipment of patients with SARS-CoV-2 disease treated who require admission to the Intensive Care Service. Smears will be taken from surfaces and personal protective equipment (PPE) and RT-qPCR will be performed to detect the presence of SARS-CoV-2. In addition, RT-qPCR positive samples will be cultured in Vero E6 cells to determine the presence of infectious virus.",2020,-99,IR-HUVH (INSTITUTO DE INVESTIGACION HOSPITAL UNIVERSITARI VALL D'HEBRON),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C10583,COV20_01081,Simulation and evaluation of the transmission dynamics of the SARS-CoV-2 virus in Spain,"This project aims to build its own and realistic model of society to study the transmission dynamics of the SARS-CoV-2 virus in Spain. The model is based on the random movement through the Metropolis Monte Carlos method of a large number of individuals (from 1000,000 to 1,000,000) who interact in certain interconnected scenarios whose parameterization tries to describe the different social collectivities of the people (work , school, family, etc). An extended SIR model will be used, for the characteristics of the individuals and by means of an adequate calibration with the available data, the values of the effective reproduction number and time of generation of the virus in each social layer will be obtained, assessing the validity of possible scenarios and measures to control the epidemic.",2020,-99,UNIVERSIDAD NACIONAL DE EDUCACIÇÿN A DISTANCIA -- UNED,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C10584,COV20_01265,Structural analysis of SARS-CoV-2 membrane proteins for the design of new inhibitors of viral assembly.,"The highly pathogenic human respiratory coronaviruses of the SARS family (SARS-CoV, MERS, and SARS-CoV-2) cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. The fundamental step in the replication and dissemination of the virus is its complete assembly in the intermediate region between the ER and the Golgi (ERGIC in English), which depends on protein-protein interactions between the structural viral proteins, mainly intramembrane interactions. However, the complexity of this type of interaction and the lack of structural information has, to date, made it impossible to understand how CoV viruses are assembled and to be able to design therapeutic tools to prevent it. With the achievement of this project, we will provide structural information on these interactions to the scientific and pharmaceutical community as a first step to achieve their inhibition and subsequent viral assembly.",2020,-99,Agencia Estatal Consejo Superior de Investigaciones Científicas,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis", +C10585,COV20_01275,VirionBreak: Dynamic calculation of the SARS-CoV-2 capsid for destruction by resonance,"The objective of the project is to carry out a structural dynamic analysis of the SARS-CoV-2 virus capsid in order to obtain its frequencies and eigenmodes of vibration, and to determine the characteristics of a radio frequency emission that could cause its collapse. These results will define the design parameters of an emitting device (probably microwaves in the SHF and EHF bands of the electromagnetic spectrum) that allows the virus capsid to be totally or partially destroyed by induced resonance. In your case, the construction of a prototype and its subsequent manufacture could be done in a short time and with low costs. The device could be used for prophylactic purposes immediately for the disinfection of inert material and contaminated biological waste. In case the vibrational frequencies and the energy required to cause the destruction of the capsid are innocuous, the same principle could also be applied for therapeutic treatment.",2020,-99,Universidad de A Coruña,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C10586,COV20_00644,Treatment of patients with COVID-19 and non-severe pneumonia without hospital admission criteria: randomized clinical trial Protocol Code: COME-CLEAN EUDRACT 2020-001962-12,"Objectives: to evaluate the effectiveness of 4 active treatment regimens in monotherapy (hydroxychloroquine, Prednisone, Azithromycin, or Colchicine) versus placebo in patients with COVID-19 with non-severe pneumonia without criteria for admission measured as hospital admission or death in the following 2 weeks after the start of treatment; evaluate and compare the safety of treatment guidelines at 28 days and describe the changes that occurred in the perception of health status at 12 weeks and analyze the impact of various clinical and sociodemographic factors on these potential changes. Design: Randomized, multicenter, double-blind, placebo-controlled clinical trial. N = 1711. Intention-to-treat analysis.",2020,-99,Hospital Universitario Fundación Alcorcón,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C10587,COV20_01385,Study of the potential impact of COVID19 on pets and lynxes.,"A consortium with great experience in sanitary surveillance and control has been created and designed a wide sampling of domestic animals (dogs, cats, ferrets) and wild animals (lynxes), some with epidemiological and clinical information and the possibility of follow-up, in 5 CCAA that represent 75% of human cases of COVID19 in Spain. The samples (saliva, serum, respiratory and rectal swabs and special skin sponges) and the epidemiological survey will be collected by the established veterinary network. They will be analyzed in VISAVET (BSL3) by means of an ELISA for antibodies against COVID19, RT-qPCR, isolation, viral and immunological characterization and differential diagnosis. Likewise, experimental infections will be carried out to assess the infection and viral spread in cats. This project will make it possible to know the presence or not of COVID19-positive animals and their potential reservoir mechanisms and viral release.",2020,-99,Universidad Complutense de Madrid,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C10602,170356,"Rapid, Low-cost Diagnostics and Deployable Surge Capacity for COVID-19","The outbreak of the coronavirus, first identified in Wuhan, China, highlights the importance of the capacity for a rapid and nimble response to infectious disease. As we have seen, the world in highly interconnected and outbreaks in one region quickly become global concerns. Diagnostics are a key tool in the fight against spread of the virus, allowing frontline responders to quickly triage patients. Over the past five years, our team has developed low-cost and de-centralized paper-based diagnostics that are simple to use and easy to distribute. During the Zika virus outbreak, we developed diagnostics within weeks and have since completed patient trials in Latin America showing performance equal to the gold standard CDC tests used in clinical labs (sensitivity equal qPCR test, 98.5% accuracy). These diagnostic, programmable by design, thus hold promise for managing future outbreaks. Seeking to contribute to the COVID-19 outbreak response, we have already begun the development of diagnostics for the virus and anticipate having validated tools within a month. Here we propose the following project to create a deployable diagnostic infrastructure for the virus: 1) A lab-in-a-box kit that can provide diagnostic surge capacity for COVID-19 (14,000 tests), 2) A package with the ""pop-up capacity"" to manufacture the diagnostics on-site for sustained response to the outbreak and 3) A point-of-need test for rapid screening of patients (e.g. cruise ships, airports). Such tools are important in Canada but are especially so in countries where health care system do not have the resilience to handle a large outbreak. We have assembled a team of researchers from four countries with expertise in virology, diagnostics technologies and delivering impactful research outcomes. Our goal is a diagnostic platform capable of providing the capacity to respond to COVID-19 here in Canada or aboard, and the companion technologies, protocols and training to ensure effective deployment.",2020,2022,University of Toronto,740000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C10603,170380,Developing integrated guidelines for health care workers in hospital and primary healthcare facilities in response to Covid-19 pandemic in Low- and Middle-Income Countries (LMICs),"The proposal responds to the CIHR call regarding public health responses to the 2019 novel coronavirus (Covid-19) pandemic. We recognise the gap in LMICs where there is an under financed health system and low capacity of health care workers (HCWs) in hospitals, public and private primary care facilities and the community/ NGO to respond to the pandemic. The World Health Organization (WHO) has produced technical guidance, but the guidance documents are broad, they have to be updated with new developments, and translated into guidelines for HCWs, i.e., doctors, nurses and community health workers for hospitals, primary care and community in LMICs. Here we choose the Philippines and Sri Lanka because they both reported Covid-19 cases, and we can quickly mobilize resources. We aim to develop an integrated plan for HCWs to respond to the pandemic, as well as role-specific guidelines to manage Covid-19 suspects and cases regarding hospital patient flow, infection control, patient supervision and support in communities. We will learn from frontline experiences in China and update our understanding. We will work with policymakers, HCWs and NGOs in the Philippines and Sri Lanka to develop the guidelines and training modules. We will pilot test the tools for feasibility and acceptability among HCWs in the Philippines, adapt in Sri Lanka, and generate a generic version for LMICs to respond to Covid-19 and any future similar pandemic. Our integrated response strategy aims to update skills of HCWs, reduce patient overload at hospitals, avoid hospital transmission, reduce community transmission and public panic, provide patient support and reduce stigma. Our professional team consists of researchers from Canada, the Philippines, and Sri Lanka. The team has strong related experience and can quickly produce a draft guideline and materials within 2 months and finalize all work in 24 months.",2020,2022,University of Toronto,368659.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,South-East Asia | Western Pacific,,,,Canada,Philippines | Sri Lanka,"Infection prevention and control | Policies for public health, disease control & community resilience",IPC in health care settings | Approaches to public health interventions,2020 +C10604,"172302, 175547",Therapeutic approaches to SARS-CoV-2 and other pathogenic coronaviruses [Added supplement: COVID-19 Variant Supplement],"Coronaviruses can cause serious diseases in humans and animals. Over that last two decades, we have seen the emergence of three deadly coronaviruses, the most recent of which SARS-CoV-2 is still spreading rapidly. Antivirals developed for other viruses are presently being tested in clinical trials in China, but there is no indication that these drugs will work against SARS-CoV-2. Currently, public health measures and quarantine are the only means to limit spread of SARS-CoV-2. As such, antiviral therapeutics and vaccines are both desperately needed to mitigate the effects of SARS-CoV-2 and future coronavirus outbreaks. Here, we present a strategy for testing novel antiviral drug candidates and vaccines as well as molecular tools to understand SARS-CoV-2 biology. By focusing initially on drugs already approved for use in humans for other indications, our goal is to identify compounds with activity against SARS-CoV-2 that can be rapidly approved for use in the clinic. In addition, our expertise in immunology and vaccinology against coronaviruses positions us very well for developing novel vaccine candidates. Finally, we will create molecular tools including modified SARS-CoV-2 viruses. Some of these tools which will not require high level containment, will be made available to a wide group of researchers so that they can also screen for antiviral compounds and study virus biology without the need for specialized containment facilities.",2020,2022,University of Alberta,777873.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C10607,"172634, 175538",The role of interleukin-10 responsiveness in lung inflammation in SARS CoV2 infection [Added supplement: COVID-19 Variant Supplement],"A subset of patients infected by SARS CoV2 respond with overproduction of inflammatory cytokines which contribute to their acute respiratory distress and morbidity. This ""cytokine storm"" results from the imbalance between inflammatory and anti-inflammatory mechanisms. One of these mechanisms involve inflammatory macrophages which produce cytokines such as interleukin-6 and interleukin-1, and anti-inflammatory, regulatory macrophages which predominantly produce the anti-inflammatory cytokine interleukin-10 (IL10). IL10 acts on the inflammatory macrophages to temper their response. We propose to examine whether the regulatory, IL10-producing macrophages in the lung are producing appropriate levels of IL10, or whether the inflammatory macrophages are impaired in their ability to respond to IL10. We will also assess whether a small molecule SHIP1 agonist which activates the intracellular protein SHIP1 like IL10 does, can mimic the action of IL10 and reduce inflammation in SARS CoV2 infection.",2020,2022,University of British Columbia,149952.99,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C10608,172651,Broad-spectrum Antiviral Nasal Spray to Prevent and treat Infection by SARS-CoV2 and Seasonal Respiratory Viruses in High Risk Patients and Health Care Providers,"Respiratory virus infections kill hundreds of thousands of people a year around the World. During pandemics this number can increase by over 100-fold. We are developing a nasal spray that has a compound in it that is antiviral against a broad spectrum of different pandemic and seasonal viruses. This antiviral, that we have named RespVirex targets the central replication engine of most viruses, called the polymerase. That means that if the central engine is stopped then the infection is slowed or it is prevented entirely. The throat is the first place that respiratory viruses take hold in the body. Therefore, we are developing RespVirex into a nasal/throat spray and aerosol that can be conveniently dosed by health care professionals and high risk patients to protect them from a broad range of viruses that circulate every flu season and during pandemics. RespVirex is being tested by an international team across Canada and at the Institute Pasteur in Senegal to test its usefulness on African SARS-CoV2 and other tropical viral infections.",2020,2021,University of Alberta,487585.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Other,International Development Research Centre (IDRC),Canada,Americas,Americas,Africa | Americas,,,,Canada,Canada | Senegal,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C10609,"172653, 175504, 175575","Bespoke transition state analog inhibitors of SARS-CoV-2 3CL and PL proteases [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","SARS-CoV-2 is devastating global health and economies. Rapid development of antiviral drugs is critical to treat disease in the short term and beyond. Logical antiviral targets are the proteases 3CLpro and PLpro, responsible for processing of long chains of linked viral proteins produced during viral reproduction. 3CLpro and PLpro are enzymes that harness pac-man like activity to clip the chains into individual proteins. This cleavage process is essential for formation of new disease causing virus. If you block the pac-man activity, you stop the virus in its tracks. Similar types of viruses have been targeted very successfully by drug development in other important global viruses such as HIV. Understanding inhibitor binding to 3CLpro and PLpro at the atomic level is central to antiviral drug development. We are harnessing our significant expertise in xray crystallography and single particle cryoEM, biophsyical techniques that allow us to determine atomic pictures of these proteases in the presence of bound drug. Leveraging our prior work on similar enzymes with international leading antimicrobial pharmaceutical teams we have identified tight binding drug leads that take advantage of the unique features of these enzymes. We aim to optimize these compounds through structure-guided techniques (using our atomic blueprints so to speak) and the antiviral drug discovery pipeline of our industry partner.",2020,2022,University of British Columbia,436155.84,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C10610,172686,Evaluating the Governance of Emergent Pandemic Zoonoses: A Systems and Legal Analysis of Wildlife Markets,"Although mitigating the current pandemic is critically important, a governance response is needed to prevent future pandemics. We need actionable evidence that focuses on the regulation of wildlife trade from which SARS and SARS-Cov2 are believed to have emerged. Specifically understanding the social, legal and cultural dynamics that affect the regulation of wildlife markets in countries where zoonotic epidemics (Ebola) and pandemics (SARs, and SAR CoV-2) emerged, including China, the Democratic Republic of the Congo and the Philippines. Therefore, the purpose of this project will be to evaluate the governance gap in stewardship of international wildlife trade supply chains given their implications for food and health security by analyzing the intersection of global biodiversity, environmental, agricultural and public health governance systems. Within each participating country an institutional and legal epidemiologic analysis will provide policy surveillance and mapping of international and national policy. A systems analysis will be used to identify local contextual interdependencies among laws, regulations, and their implications for the behaviour of social and political actors and communities supplemented by in-depth qualitative case studies. The empirical evidence from these analyses will be integrated into a report and set of policy recommendations that will be utilized in a process to inform the development of a policy design and implementation toolkit for international organizations, national and local stakeholders who will be engaged throughout the research process.",2020,2020,York University,328927.23,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Other secondary impacts | Health leadership and governance,2020 +C10611,172728,Establishing A Research Platform for Investigating and Optimizing PPE Filtration/Barrier Efficiencies Against Aerosolized Bacteria and Viruses in Clinical Healthcare Settings,"The state of emergency brought about by the pandemic has mercilessly exposed the shortfalls of our healthcare system, one of the most pressing being the severe shortage of personal protective equipment (PPE). To meet an urgent need for PPE, the government has taken several measures, such as increased import, repurposing of existing manufacturing lines, and approving methods of decontamination and re-use. Whether imported, locally manufactured, or decontaminated and reused, protective gear must provide an effective barrier against infectious aerosols. However, currently no Canadian lab has the capability to quantify the effectiveness of PPE against biological aerosols in accordance with regulatory standards, which means PPE samples must be sent to labs in the US, with lead times of weeks to month. We have addressed this issue by developing a standardized test setup for determining the barrier efficiency of PPE material against biological aerosols. We propose to expand and extend our Nationally unique workflow to address 3 critical gaps in knowledge and, as a result, create knowledge and capacity for developing a National standard for protective gear: (1) Quantification of filtration efficiency of locally manufactured and imported PPE against aerosolized viruses and correlating the data to standardized bacteria filtration efficiency tests, with focus on suppliers to the 5 major hospitals in Hamilton and local industrial partners, as a representative of the PPE market in Ontario; (2) Investigating the effect of Health Canada-approved sterilization/reuse protocols on barrier of PPE material against airborne viruses, both for single use PPE and PPE designed to be reusable (e.g., cloth masks); (3) A clinical study focused PPE fit, specifically focused on fit based on sex and ethnical background, that will inform general public and policy makers of whether the current design of PPE meets the needs of the entire Canadian population and match our rich cultural landscape.",2020,2020,McMaster University,205233.6,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C10612,"173022, 175530","Vaccine efficacy in nonhuman primates against SARS-CoV-2: protection, cross-protection and immune enhancement [Added supplement: COVID-19 Variant Supplement]","In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. Since then (in only the last 5 months) this virus, has caused a global pandemic resulting in 4.2 million cases and over 288,000 deaths. Quarantine measures have not been sufficient to interrupt transmission despite near world-wide unprecedented disruptions of normal activities. Since its identification we have been working on making a vaccine to prevent infection with SARS-CoV-2. This vaccine contains a portion of the spike protein (the protein that is present on the surface of the virus) and when delivered to animals, induces an immune response. So far, we have shown that this vaccine can cause an immune response in ferrets, and early data suggests that to is also protective. To ensure that this vaccine is safe, immunogenic and effective we propose to test it in a nonhuman primate model of SARS-CoV-2. Typically nonhuman primates are the animal model that most closely resembles what happens in humans. To do this rapidly, we will vaccinated animals at the National Microbiology Laboratory with our vaccine to determine whether it induces the kind of immune response we want to see. Namely, whether it induces antibodies that are capable of blocking infection - called neutralizing antibodies. Finally, we want to demonstrate that this vaccine actually protects the animals from infection and does not cause any deleterious events, so animals will be infected and monitored to determine whether the vaccine stops infection. Subsequent experiments to support this data will be performed at VIDO-InterVac. Together this work will increase the capacity to assess other vaccine concepts that are being worked on across Canada to identify the best approach to stop transmission of SARS-CoV-2.",2020,2022,University of Saskatchewan,944549.98,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C10613,173062,I accompany COVID-19: a participatory action research project testing an innovative virtual support modality developed according to the model of compassionate communities in order to understand and prevent complicated bereavement in the context of a pandemic,"Public health measures to curb the spread of COVID-19 have tragically disrupted the support of people at the end of their life as well as the process of mourning their loved ones. To date, the peculiarities of bereavement in the context of a pandemic have not been documented by any study. However, several writings allow us to conclude that this context involves many factors likely to generate an increase in complicated bereavement. At the same time, the confinement and physical distancing measures are disrupting the methods of psychological support intended for the bereaved. The main community organizations offering group support have had to suspend their activities. Professional individual psychotherapy services can be offered virtually, but pose a definite challenge in terms of accessibility and equity given the costs they generate for bereaved individuals whose job security is often affected. In April 2020, our team received a start-up grant to set up the ""J'accompagne"" project; a participatory action research project developed using the compassionate communities approach. These funds allowed us to collect empirical data through in-depth qualitative interviews with 13 participants bereaved by COVID-19 and thus better understand their support needs. In the context of this request, we wish to: continue and deepen our understanding of bereavement in the context of a pandemic by increasing the size of our sample, add a longitudinal component by documenting the evolution of the bereavement process of these participants in order to identify the factors likely to contribute to possible complications of bereavement and document the effectiveness of an alternative and accessible virtual support modality for bereaved in the context of the pandemic.Les mesures de sante publique afin d'enrayer la propagation de la COVID-19 ont bouleverse de maniere tragique l'accompagnement des personnes en fin de vie ainsi que le processus de deuil de leurs proches. A ce jour, les particularites du deuil en contexte de pandemie n'ont ete documentes par aucune etude. Toutefois, plusieurs ecrits permettent de conclure que ce contexte implique de nombreux facteurs susceptibles de generer une augmentation des deuils compliques. En parallele, les mesures de confinement et de distanciation physique bouleversent les modalites de soutien psychologique destinees aux endeuilles. Les principales organisations communautaires offrant du soutien de groupe ont du suspendre leurs activites. Les services professionnels de psychotherapie individuelle peuvent s'offrir de maniere virtuelle, mais posent un defi certain en termes d'accessibilite et d'equite compte tenu des couts qu'ils engendrent pour les individus endeuilles dont la securite d'emploi est souvent affectee. En avril 2020, notre equipe a beneficie d'une subvention de demarrage afin de mettre sur pied le projet << J'accompagne >>; un projet de recherche action participative developpe selon l'approche des communautes compatissantes. Ces fonds nous ont permis de recueillir des donnees empiriques par l'entremise d'entretiens qualitatifs en profondeur aupres de 13 participants endeuilles des suites de la COVID-19 et ainsi de mieux comprendre leurs besoins de soutien. Dans le cadre de la presente demande, nous souhaitons : poursuivre et approfondir notre comprehension du deuil en contexte de pandemie en augmentant la taille de notre echantillon, ajouter un volet longitudinal en documentant l'evolution du processus de deuil de ces participants afin de cerner les facteurs susceptibles de contribuer aux complications possibles du deuil et documenter l'efficacite d'une modalite de soutien virtuelle alternative et accessible destinees aux personnes endeuillees dans le contexte de la pandemie.",2020,2021,Université du Québec à Montréal,57885.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C10614,173063,Our Virtual Reality: Rapidly Responding to Changing Mental Health Needs among Children and Adolescents,"COVID-19 is affecting child and youth mental health and the ability to access to mental health services. IWK Mental Health and Addictions services changed quickly from in-person to virtual (video or teleconference) services in response to the pandemic and need for physical distancing. Responses from patients and families have not been predictable, and demand for services is at a record low. We had expected many more people to need care, however, fewer are doing so despite our concerns about distress and worsening mental health due to COVID-19. We need to understand why. Some youth and families are waiting until things are ""back to normal"" to start or continue their care. Parents or caregivers may be too overwhelmed with pandemic-related concerns to seek care for their children. Rural locations may lack internet services to support virtual care. And, while for some youth and families virtual care has improved access to services, some may not have the privacy or safety in their homes needed to speak to their clinician. Early feedback from clinicians has identified challenges in providing virtual care, but has also identified opportunities to better engage, understand, and support youth and families. We propose to: 1.Describe the mental health care needs of children, adolescents, and families in Nova Scotia during the COVID-19 pandemic; 2.Evaluate the barriers and facilitators of the delivery of virtual mental health care, including the views of children, adolescents, families, and service providers. We anticipate the need for services will increase with or without new waves of COVID-19. We aim to match services to those who need them most. Better understanding mental health needs and virtual care will help us to plan rapid responses to changes. This will help us to identify and treat children who need mental health care in a timely way, support their ability to go to school, and prevent long-term problems.",2020,2020,Dalhousie University,148571.42,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10615,173064,Alterations in Prescribing of Opioid Agonist Therapy due to the Pandemic (ALT-POP) Study,"Even before the COVID-19 pandemic, Canada was going through one of its worst-ever public health crises: the overdose crisis. Unfortunately, the pandemic seems to have further worsened the overdose crisis, with rates of overdose deaths increasing since the pandemic began. The primary medical treatment used to help people stop using illicit opioids is medication to help reduce cravings and prevent overdose. These medications, referred to as opioid agonist therapy, often require clients to go frequently to the pharmacy and their clinic, which makes it more difficult to practice physical distancing to reduce the risk of getting COVID-19. In order to ensure people have access to these life-saving medications during the pandemic, several changes were made to how doctors and nurses provide them in some cases. These changes included less frequent visits to the pharmacy and reduced monitoring such as urine drug tests. While this may make taking the medications easier for some people, it is also important to make sure the changes are safe and do not have any unintended consequences. Our proposal will evaluate how the changes in prescribing of medications for opioid use disorder as a result of COVID-19 impacted the clients who take them. We will use multiple study methods including Ontario-wide administrative health data as well as surveys and interviews with healthcare providers and people with lived expertise related to the use of these medications. The results of this study will be used to decide how to best provide these medications going forward in order to reduce overdose death and treat opioid use disorder during the pandemic, and, in general.",2020,2020,Unity Health Toronto,143396.19,Human Populations | Other,Unspecified,Unspecified,Unspecified,Drug users,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C10616,173065,"Evaluation of innovative risk mitigation services in the context of dual crises of COVID-19 and overdose among people who use opioids in Vancouver, BC","The province of British Columbia (BC) has been praised for having successfully flattened the curve of novel coronavirus infections early. However, this is in stark contrast with the status of its opioid overdose crisis, another health emergency plaguing BC since 2016. In May 2020, BC recorded 170 overdose deaths, which was the highest number ever recorded for a single month in Canadian history. COVID-19-related public health measures have been expected to pose significant challenges to addressing the overdose crisis that is primarily driven by the toxic illicit drug supply. Physical distancing measures risk interrupting access to key overdose prevention services, particularly opioid agonist therapies (OAT) for people with opioid use disorder. Border closures risk straining traditional illicit drug supplies (e.g., heroin), making the illicit drug market more toxic. In response, BC rapidly initiated a series of innovative measures to address the dual crises of COVID-19 and overdose. Specifically, OAT prescription guidelines have been expanded to encourage OAT prescribers to consider a range of means (e.g., take-home doses, medication delivery) to prevent disruption of OAT. Additionally, pandemic prescribing allowed physicians and nurse practitioners to prescribe certain pharmaceuticals (e.g., opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these innovative interventions have not been evaluated. Our proposed research aims to fill critical knowledge gaps by examining the reach and impacts of pandemic prescribing and expanded OAT prescription services. Through this work, we seek to inform efforts to improve the delivery and effectiveness of the interventions.",2020,2020,British Columbia Centre on Substance Use,152632.8,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Michael Smith Foundation for Health Research,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C10617,173066,Identification of Factors to Improve Effectiveness and Implementation of a Multi-faceted COVID-19 Mental Health Intervention: Follow-up to the SPIN-CHAT Trial,"The COVID-19 pandemic has spread rapidly, seen an increasing number of deaths, and taxed economies. Fears due to risk of infection, collapsing healthcare systems, unknown isolation/restriction periods, and that resources will be insufficient have resulted in poor mental health outcomes. Such outcomes may be worse among those with pre-existing medical conditions. Individuals with the autoimmune disease, scleroderma are representative of other vulnerable groups in terms of COVID-19 mental health ramifications due to their frailty, pre-existing respiratory concerns, and suppressed immune systems. Governments, organizations, and researchers have suggested that multi-faceted interventions are required during this time. Yet, only one study has tested such an intervention during COVID-19: The Scleroderma Patient-centered Intervention Network COVID-19 Home-Isolation Activities Together (SPIN-CHAT) Program, which was rapidly designed and tested with 172 participants. The SPIN-CHAT Program consisted of 3 group sessions/week over 4 weeks. Trained facilitators led the sessions and professional educators provided mental health, physical activity, and other anxiety and worry-management strategies. Early results suggest the intervention may be effective. As this was a practical program, with tremendous potential to be tested again, modified for other vulnerable populations, and eventually implemented into care, exploring how to optimize the SPIN-CHAT Program and study is necessary. Collecting multiple perspectives from participants, facilitators, professional educators, and trial management can provide in-depth information from differing viewpoints to explore benefits accrued, identify aspects of the SPIN-CHAT Program and study were and were not helpful, determine acceptability, and guide improvement efforts. Ultimately, this project will identify ways to improve the SPIN-CHAT Program and study to ensure a greater number of vulnerable individuals can receive this intervention.",2020,2020,Lady Davis Institute for Medical Research,68774.27,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Approaches to public health interventions,2020 +C10618,173067,COVID-19 Effects on Mental Health and Service Provision Effects on Children and Families: The MY LIFE Experience,"Children with co-occurring physical and mental illness, or multimorbidity, have poorer quality of life and use more health services. The parents of children with multimorbidity also experience poor mental health. These burdens are likely amplified by the COVID-19 and subsequent countermeasures to reduce transmission such as school closures, cancelled medical appointments, and physical distancing. Understanding the extent to which COVID-19 has affected the mental health of these vulnerable children and their families is needed to support these individuals during COVID-19 and plan for future crises. Further, the advent of virtual mental health care such as video conferencing has given rise to new challenges. Best practices suggest that health care for children should be family-centred, focusing on the needs of the child in the context of their family environment. But, it is unknown if the delivery of virtual health care is perceived by children with multimorbidity and their parents as family-centred and how virtual health care in the era of COVID-19 impacts mental health. We will engage families already recruited in our ongoing longitudinal study child multimorbidity to investigate the changes in the mental health of children and parents in the time prior to, during, and after COVID-19 countermeasures; examine if virtual mental health care, in response to COVID-19, is family-centred, and understand child and parent perceptions of health care needs for individual and family mental health. Our study includes 263 families who will complete mail surveys and participate in online qualitative interviews that will ask about mental health care needs in the context of COVID-19. Because our sample of families is already engaged with our research team, we can quickly obtain and summarize research findings that can be used by health professionals, families, and policy makers to allocate resources to best support the mental health of children and their families during COVID-19.",2020,2020,University of Waterloo,126225,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10619,173068,Best practices for pharmacists in medication management for opioid use disorder - expanding access and optimizing integration of care during COVID-19 pandemic and going forward,"Pharmacists provide essential medication management services for people with opioid use disorder. Actions taken during the COVID-19 pandemic must balance the risks of community viral transmission with patient and community safety as it relates to medication treatments (e.g., risk of opioid overdose, risk of treatment interruptions). Significant changes in the model of care for medication treatments (e.g., methadone and buprenorphine) have occurred, and pharmacists have been at the forefront of this transformation. The dual effects of the COVID-19 pandemic and opioid crisis has created an urgent need to assess the changes and challenges to these services across Ontario. To address these needs, this project proposal has the following objectives: 1.To assess changes due to the COVID-19 pandemic, establish current state, and identify challenges and facilitators in pharmacist medication management services for people with opioid use disorder in Ontario. 2.To develop best practice guidance for pharmacists across the spectrum of medication management services for people with opioid use disorder to mitigate the impact of COVID-19 and to make recommendations for adapting, advancing and expanding access to medication management services for people with opioid use disorder, leveraging pharmacist expertise in collaboration with health care partners going forward. The current global COVID-19 pandemic is exacerbating existing limitations in pharmacist services delivery for people with opioid use disorder. We will identify needs, establish current best practices, and plan for improvements as we adjust pharmacy practice now and into the future, in order to meet the needs of people with opioid use disorder, prevent harms and reduce overdose deaths.",2020,2020,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,128363.18,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10620,173069,Equity of virtual mental health care uptake for children and youth during the COVID-19 pandemic.,"The COVID-19 pandemic has transformed the way health care is delivered. To reduce the risk of COVID-19 transmission through unnecessary in-person visits to health care facilities, many health care providers are offering virtual visits. This has been facilitated through the creation of telemedicine physician billing codes and increased availability of virtual health platforms. Virtual mental health care has been proposed as a strategy to address the longstanding and growing gap between patient need and available mental health care resources, especially in underserviced and rural areas. However, it remains underused by both patients and physicians. Currently, there is a critical knowledge gap regarding the uptake of virtual mental health care during the COVID-19 pandemic for children and youth previously receiving care and those who are accessing it for the first time. Virtual care may address significant barriers to care including geography, time, and cost, with the pandemic acting as a stimulus for uptake. However, this uptake may not be universal, with some populations (e.g. those with limited reliable internet and language proficiency, or low income) continuing to face barriers in access. As a result, a shift to virtual care with the pandemic may have further widened existing health inequities. Using the well-established linked administrative and health data systems in Ontario, we will compare in-person and virtual mental health care visits for children (<18 years) with ongoing and new mental health care needs before and after the onset of the COVID-19 pandemic. We will illuminate whether the pandemic has widened inequities in access to care for priority populations. Namely, young people from low income neighbourhoods, rural areas, and who are refugees. Given the shift to this modality will likely be lasting, our data will inform ways in which virtual mental health care can be implemented in a more equitable and systematic way to better match patient need.",2020,2020,Hospital for Sick Children,134266.68,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Rural Population/Setting,Minority communities unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10621,173070,Identifying Effective Mental Health Interventions and Populations in Need: A COVID-19 Living Systematic Review,"There will be serious mental health implications from COVID-19 that extend beyond the first outbreak for many people. Addressing mental health needs requires understanding the nature and extent of mental health ramifications, factors associated with vulnerability, and evidence on effectiveness of interventions that may be rapidly employed to prevent or address mental health concerns. Studies from COVID-19 are published rapidly, but many are of dubious quality. Thus, curation of this growing evidence base is urgently needed to provide practitioners and policy makers with clear, coherent evidence synthesis. Living systematic reviews are systematic reviews that are continually updated and provide ongoing access to results via online publication. They are logistically challenging, but provide value beyond conventional systematic reviews in situations where (1) important decisions need to be made; (2) uncertainty in existing evidence poses a barrier to decision-making; and (3) new evidence is emerging rapidly. Such a review is urgently needed to guide mental health care during and following COVID-19. Our research team has expertise in high-impact evidence synthesis research (https://www.depressd.ca/teammembers). Our protocol has been made public on the Open Science Framework (https://osf.io/96csg/). An editorial on the project has been published and will be indexed in major search databases to announce that the living systematic review will provide ongoing, rigorous curation of COVID-19 mental health evidence. We have already launched initial database searches, are receiving daily search updates, and have already reviewed > 12,000 articles. We have published initial evidence online (https://www.depressd.ca/covid-19-mental-health). Important evidence will be published in the months to come. It is crucial to maintain funding for this important project to incorporate the higher quality evidence that is beginning to be made available.",2020,2021,Lady Davis Institute for Medical Research,152874.54,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10622,173071,Online 1-Day Cognitive Behavioural Therapy-Based Workshops for Postpartum Depression,"Postpartum depression (PPD) affects up to 1 in 5 women and is associated with costs of $150,000 per case over the lifespan. Under normal conditions, just 1 in 10 women with PPD get evidence-based treatment, a situation that has worsened substantially during COVID-19. The pandemic has also significantly increased women's exposure to factors that worsen PPD (e.g., more responsibilities at home, increased isolation, loneliness, life stress and partner conflict). While social distancing measures reduce COVID-19 spread, they have made it more difficult for women to access protective influences such as medical care and social and practical support. Innovative interventions capable of reaching large numbers of women safely are urgently needed to reduce the adverse effects of PPD on women, their partners, and their children. The purpose of this study is to test the effectiveness of a self-referred Online 1-Day CBT-Based Workshop for PPD. We will conduct a Canada-wide randomized controlled trial where 264 women will be recruited to receive either the Online 1-Day CBT-Based Workshop right away (treatment group) or be put on a waitlist to receive the workshop 6 weeks later (waitlist control group). We will compare the effect of these Online 1-Day Workshops on levels of maternal depression and anxiety, women's relationships with their partner, and mother-infant attachment in the treatment and waitlist control groups. We will also assess the cost-effectiveness of the intervention. Only interventions that are safe and that can be rolled out on a large scale can have a significant positive impact on PPD at the population level during the COVID-19 pandemic. To achieve this objective, a shift is needed toward treatments that can reach large numbers of women safely and efficiently. Self-referred Online 1-Day CBT-Based Workshops reduce many of the barriers to treatment that currently exist, and can help women and families immediately both in Canada and around the world.",2020,2020,McMaster University,152668.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10623,173072,Personality as a predictor of emerging adults' poor adherence and psychological distress to public health measures for controlling COVID-19 viral spread: Empirical evidence and intervention efficacy,11]. And some who are adhering appropriately appear very psychologically distressed in response to these viral containment measures,2020,2020,Dalhousie University,153000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C10624,173073,Mental Health Needs of LGBTQ2S Youth and Young Adults During the COVID-19 Pandemic,"Youth and young adult serving organizations are facing numerous challenges meeting the needs of youth during the COVID-19 pandemic. Many services typically available to youth in crisis have had to close their doors and are no longer accepting new clients, making it especially difficult for youth to access the services and support they rely on. A recent report focused on the youth-serving sector found that sexual and gender minority youth are experiencing ongoing challenges getting their basic needs met, including food and shelter during the COVID-19 pandemic but little is known about the unmet mental health and substance use needs in these populations. In order to address these gaps, we will leverage an existing cohort of 1500 youth and young adults who identify as LGBTQ2S to understand their specific challenges and unmet mental health and substance use service needs during the COVID-19 pandemic using a longitudinal approach. We will use an innovative machine learning model on our data to identify complex intersectionalities--the way that multiple individual characteristics influence health and behaviour in ways that are difficult to identify with conventional statistics. Finally, in coordination with Rainbow Services at CAMH, our Youth Advisory Board, and our National Community Advisory Board of stakeholders and community organizations, we will use a design-based method called a design charette to allow 40 youth and young adults, who could be potential clients, design adaptations to existing programs and develop new programs that will help meet the needs of sexual and gender minority youth and young adults during the COVID-19 pandemic.",2020,2020,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,152235,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Sexual and gender minorities | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10625,173074,Acceptability and Impact of a Prenatal Internet Intervention for Promoting Maternal Mental Health in the COVID-19 Context,"Pregnancy and the postpartum are known periods when mothers are at heightened risk for psychological distress, including elevated depression, anxiety and stress. With the COVID-19 outbreak concerns related to fear of infection, maternal and infant health, financial stresses and social isolation resulting from extraordinary public health measures to slow the spread of COVID-19 are likely to exponentially increase psychological distress in expectant mothers. A strong body of research has shown that even mild to moderate maternal emotional distress during pregnancy adversely impacts mothers and their offspring. Given the likely increase in emotional distress experienced by pregnant women during the current COVID-19 pandemic, there is an urgent need to promote the mental health of pregnant women with programs that can be delivered remotely. Out team has been ahead of the curve in recognizing the need for developing evidence based online care strategies. We have developed a bilingual prototype website entitled HealthyMoms which is comprised of accurate and understandable information on the impact of stress, depression and anxiety during pregnancy. Tools to promote emotional well-being and healthy behaviours during pregnancy are provided. The present COVID-19 crisis and the expected mental health fallout from the crisis presents an important opportunity to evaluate the potential of our online platform to address the mental health needs of pregnant women and reduce the risk of perinatal depression. Our approach to promote maternal mental health during pregnancy with a far-reaching web-based support program fills an important and urgent gap to address the short and long-term psychological impact of the COVID-19 pandemic, with the potential to positively impact maternal, infant, and family outcomes.",2020,2020,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,136139.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10626,173075,"Pragmatic trial of two novel pathways for implementation of the Better Nights, Better Days (BNBD) online program to promote and protect the sleep, mental health, psychosocial wellbeing, and family resiliency of children and families during and after COVID-19 pandemic","Consistent with worldwide findings, our recent survey of Canadian families shows that sleep has worsened in nearly 40% of school-aged children and 60% of parents since the start of the COVID-19 pandemic. We previously demonstrated that the fully automated online program, Better Nights, Better Days (BNBD), helps parents improve their children's sleep, emotional and behavioural functioning, and quality of life, as well as their own fatigue. Over 5 interactive online sessions, BNBD encourages a 24-hour perspective of healthy daytime behaviours (e.g., exercise, reduced screen time), along with predictable and developmentally appropriate routines, to promote healthy sleep. In turn, sleep promotes resiliency and improved daytime functioning (e.g., emotional regulation, learning, attention). In our recent survey, 95% of parents thought other families who had not used BNBD would benefit from accessing the program during COVID-19. In the current proposed study, we will test how to scale-out BNBD across Canada. We will also determine if BNBD improves the sleep, mental health, psychosocial wellbeing, and family resiliency in children and their parents during and between COVID-19 pandemic waves. We will examine two referral pathways to the BNBD program. The first is a novel direct-to-consumer self-referral pathway that uses a marketing approach. The second uses a traditional healthcare provider referral to the program. We will compare the effect, access, and uptake of BNBD for different CIHR-identified priority populations and across both referral pathways. Our established BNBD program with our multi-disciplinary research, community, institutional, and industry partners, make this research study extremely feasible. Our findings will direct the launch of BNBD as a self-contained virtual program to improve sleep and wellbeing in children and families in the context of COVID-19. Findings could also be used to increase scale and spread of other virtual mental health programs.",2020,2020,Dalhousie University,137470.5,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10627,173076,"A Virtual Community promoting mental Health, psychosocial Adjustment, and peer supporT (vCHAT) for patients living with increased risk for COVID-19","In the age of COVID-19, patients with chronic heart failure (CHF) or advanced chronic kidney disease (CKD) are at increased risk of experiencing psychological distress, social isolation, and decreased quality of life. The potential threat of COVID-19 has placed increased strain on patients and family members. To overcome this challenge, an innovative program of social network support and automated digital counseling is needed to meaningfully address the mental health needs and psychosocial challenges of Canadians with increased vulnerability to COVID-19. This 12-month study will evaluate the clinical benefit of vCHAT (a program of social network support and automated digital counseling) to promote mental health for outpatients with CKD or CHF. Our team includes professionals in health and mental health care, and patient representatives. We will recruit 480 outpatients from CHF and CKD clinics at 2 hospitals in Toronto, Canada. vCHAT will provide access by internet or smart phone to chat rooms and weekly 30-minute webcast presentations or group discussions by health professionals and patient representatives, with 30-minute question-answer periods. The webcasts will be supported by resources from our previous clinical trials and organized by mental health themes such as living well in the age of COVID-19. We hypothesize that over repeated assessments at baseline, 2, 4, 6, and 10 months, vCHAT will improve mental health and quality of life, while decreasing loneliness and perceived social isolation. Analyses of vCHAT will also provide novel insight into key program features of social network support or automated digital counseling that predict positive mental health. This proposed study builds on our previous clinical trials for digital counseling and peer support. vCHAT will provide information that is essential for tailoring digital interventions to the needs of vulnerable populations in Canada, and for mitigating the secondary mental health impacts of COVID-19.",2020,2020,University Health Network,152272.49,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10628,173077,"ATTACH™ & VID-KIDS: Rapid User-Informed Web and Mobile Interface Development, Adaptation and Pilot Testing to Support Children's Mental Health and Development.","Toxic stress undermines parent-child relationship quality and puts children at risk for mental, emotional and behavioural (MEB) health and development problems. The COVID-19 pandemic has placed additional stressors on vulnerable families and dramatically impacted the delivery of support services and related research. Our aim is to build on the success of two CIHR funded in-person (home or clinic) intervention programs designed to improve parent-child relationship quality and child MEB health and development by rapidly pivoting to user-engaged design and pilot testing of two unique virtual delivery programs. ATTACH™ (Attachment and Child Health) is designed to help parents affected by toxic stress (parental depression, addictions, family violence, low-income) improve their reflective function (RF) or capacity to understand their own and their child's mental states, which can strengthen parent-child relationships and buffer the impacts of toxic stress on children. VID-KIDS (Video Feedback Interaction Guidance Program for Depressed Mothers and their Infants) is designed to help mothers with postpartum depression to be sensitive and responsive to their infants, an ability undermined by the symptoms of depression, in order to promote healthy child development. Using integrated knowledge transfer and co-design approaches, we will further develop and pilot test both virtual delivery programs for real world implementation, by evaluating the impact of the beta prototypes on children's MEB health and development. For VID-KIDS, impacts on maternal depression will also be assessed and for ATTACH™, RF will also be measured. This project will set the stage for two future tri-council randomized controlled trial (RCT) grants, expanding our research into user-engaged technology-enabled delivery of urgently needed community mental health interventions, and allowing us to rapidly scale up these parent training programs to reach a greater number of vulnerable Canadian families.",2020,2020,University of Calgary,152571.6,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10629,173078,"Stepped care solutions to reduce impact of the COVID-19 pandemic on youth living with chronic pain, their families, and health care providers: A pan-Canadian study.","The COVID-19 pandemic is one of the greatest threats to youth mental health in generations. Similar to past disasters, youth today report increased pain complaints. Without treatment, this pain will become chronic (CP; pain lasting >3 months), which already affects 1 in 5 youth and has devastating impacts on whole families. CP in childhood can trigger a wave of mental health and substance misuse issues that carry forward into adulthood. In 2019, our team revealed that ""access to pain care"" is a priority for youth with CP and families. Unfortunately, COVID-19 has only made access more difficult. CP clinics cannot see patients in person and only some can offer virtual care. Meanwhile, youth have lost access to school counselors, and physical distancing has likely worsened their mental health. The pandemic offers a once-in-a-lifetime chance to improve access to CP care moving foward. ""Stepped care"" is a promising way to do this. A good thing about stepped care is that it tailors care based on how bad a person's symptoms are. Like a ladder, a person may start with one type of care and then ""step up"" or ""step down"" to more or less intense care depending on need. We want to hear from youth, families, and healthcare professionals (HCPs) in the CP community about COVID-19 impacts. We will then create a ""stepped care"" program called Kids Pain Portal. This online Portal will increase access to CP care and ensure youth get the right treatment at the right time. Our study has four phases. In Phase 1, youth, families, and HCPs from across Canada will complete online surveys. In Phase 2, we will interview some patients, families, and HCPs from Phase 1. These surveys and interviews will tell us about COVID-19 impacts on CP care. In Phase 3, we will meet with HCPs, researchers, and family partners. There, we will create best practice recommendations for virtual ""stepped care"" in Canada. In Phase 4, we will co-design the Kids Pain Portal and ensure it is easy and satisfying to use.",2020,2021,Hospital for Sick Children,187425,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Health Personnel | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10630,173079,Stepping up to COVID-19: Examining a virtual mental health stepped care approach to addressing needs of at-risk children and families,"COVID-19 has necessitated unprecedented quarantine policies that have caused increased stress and uncertainty among Canadian families. At a time when most research is focused on the virus itself, the importance of rapid action in providing and evaluating targeted virtual family mental health interventions for high-risk groups is also paramount. Families with children with pre-existing neurodevelopmental disorders that can influence emotional and behaviour regulation (e.g. ADHD, Autism) are at enormous risk for heightened strain and deterioration, due to disruptions in routine, decreases in external social support, and multiple demands on parents. Providing opportunities for mental health support to these families is essential, with options that are flexible and matched to the family's needs. The current study will evaluate an adapted stepped-care model of an evidenced-based virtual mental health parent intervention (I-InTERACT-North; PI:Williams), an already active SickKids clinical research program with a strong record of success in virtual service delivery predating COVID-19. Stepped care models offer effective treatment and tailor treatment intensity and level of therapist involvement to families' needs. For this proposal, I-InTERACT-North is partnering with the Province of Ontario Neurodevelopmental Disorders (POND) Network (Co-PI: Anagnostou), a large well characterized diverse cohort of children and youth across Ontario with neurodevelopmental conditions impacting mental health. Recruitment will target children ages 3-9 years across four centers in Ontario (Holland Bloorview Kids Rehabilitation Hospital, SickKids, University of Western Ontario, Queen's University). Overall, the purpose of this project is to evaluate implementation of the stepped-care intervention, providing steps to match family need, in effort to mitigate further mental health risk and family dysfunction and inform program scalability during and beyond the immediate crisis.",2020,2020,Hospital for Sick Children,153000,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10631,173080,Remote Treatment of Alcohol Withdrawal: A Pilot Study,"Alcoholism is one of the most common and deadly substance use disorders in Canada. Many people seek alcohol withdrawal management or 'detox' as the first step in the treatment of alcoholism. Unfortunately, the COVID-19 pandemic has made accessing treatment more difficult as many addiction treatment centres are closed to promote social distancing and patients may be reluctant to seek care due to the risk of infection. Previous studies have demonstrated that alcohol withdrawal can be safely managed in the outpatient setting, however, to our knowledge, no studies have considered employing telemedicine (use of phone and video technology to assess patients remotely) to manage alcohol withdrawal. In this study, we propose to assess whether it is feasible to treat alcohol withdrawal using telemedicine. We plan to recruit 30 participants with alcohol addiction requiring medical withdrawal management. Participants will initially be assessed for eligibility. Clinical nurses will then monitor patients remotely using a standardized withdrawal assessment tool to guide treatment. Outcome measures will include retention in treatment, development of withdrawal complications, and patient satisfaction. Finding a new way to provide alcohol detoxification remotely using telemedicine could increase the number of patients able to access care, decrease the risk of coronavirus transmission, and improve patient satisfaction. If this intervention is found to be feasible, it could also be used to provide alcohol withdrawal management for people in remote parts of Canada without access to addiction medicine services.",2020,2020,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,142406.28,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Not applicable,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10632,173081,Reducing Risk and Promoting Health Among Vulnerable Teens and their Families in the Context of COVID-19: A Multisite National and International Implementation and Evaluation Study,"COVID-19 and the associated public health response (e.g., physical distancing) have had significant negative impacts on the mental health of youths and their families. This is particularly notable among vulnerable teens with pre-existing mental health challenges and families experiencing high levels of interpersonal conflict. Concerns that vulnerable teens may leave their family homes and be unable to return due to the risk of COVID-19 transmission are rising. During these difficult times, caregiver depression, stress, and family violence is likely to increase. Evidence-based interventions supporting vulnerable families are critical to combating these challenges. Connect is an evidence based, trauma-informed, attachment-focused program that promotes effective parenting skills (mindfulness, empathy, emotion regulation), and parent-teen collaborative problem solving. National and international studies have demonstrated that Connect reduces family conflict, caregiver depression and stress, and improves family satisfaction. Furthermore, mental health problems (oppositional behavior, anxiety and depression) are reduced amongst teens whose parents complete the program. While structured, Connect can be flexibly adapted to suit unique cultures and contexts. In response to the call for online mental services for vulnerable populations, we have created eConnect Online, a program that specifically addresses the challenges associated with parenting vulnerable youth in the context of COVID-19. The current project evaluates the challenges (related to COVID-19 or otherwise) of families at the start of the program, implementation, uptake, and evaluation of eConnect Online through a global network of researchers, health agencies, clinicians and families in developed and developing countries. As collaboration and knowledge sharing are cornerstones of this project, we will use feedback from families and service providers to inform future implementations of eConnect Online.",2020,2020,Simon Fraser University,152713.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Physicians | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C10633,173082,e-NAVIGATE: Adapting evidence-based early psychosis intervention services for virtual delivery,"Psychosis is an often frightening and disabling condition that typically manifests in adolescence and young adulthood. Early psychosis intervention (EPI) services are the standard of care for youth with psychosis, helping them to achieve recovery and avoid catastrophic outcomes. A manualized package of evidence-based treatments called NAVIGATE has been increasingly adopted by EPI programs to achieve superior outcomes and standardize care. To curb the spread of the COVID-19 pandemic, EPI services have had to rapidly transition to delivering care virtually. However, there is little evidence to support virtual delivery of EPI services. We propose to evaluate the implementation effectiveness of e-NAVIGATE, an innovative virtual adaptation of NAVIGATE. We will examine how closely it adheres to the EPI model, and what helps and harms implementation, including health equity factors, to help improve future development and implementation of the model. We will evaluate the acceptability of e-NAVIGATE to patients, family members and clinicians. A network of EPI programs across Ontario that have recently implemented NAVIGATE will serve as sites for the spread of e-NAVIGATE. This work may help increasing numbers of youth with psychosis receive high-quality care during as well as beyond the pandemic.",2020,2020,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,147934.94,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Other | Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10634,173083,Adapting a holistic program to support the mental health and wellness of front line workers providing care to homeless and street communities,"This research aims to address the mental health needs of frontline workers serving homeless communities that have been intensifying during COVID-19. Background: Canada's Chief Public Health Officer has described the sharp increase in drug overdoses and deaths an unintended consequence of COVID-19 and a worrying trend that is disproportionately affecting homeless people. Frontline workers (health providers and peer support workers, many of whom have lived experience of substance use and homelessness) are experiencing acute mental health issues as they respond to the complex trauma being experience by their clients. To maintain healthcare services and lifesaving supports, we must match the mental health needs of front line workers to services that address the secondary trauma they are experiencing so they can continue to provide effective care to the most vulnerable and marginalized members of society. In partnership with Ottawa Inner City Health (OICH), an organization that provides health care services to people who are chronically homeless, we will use a participatory, mixed methods, pre/post design to adapt, implement and evaluate an innovative series of mental health supports, and develop a framework for adapting and scaling delivery to other organizations. The mental health supports involve: 1) holistic wellness retreats, and 2) suite of mental health services (e.g., cognitive and behavioural therapy, workplace huddles, psychotherapy). Methods: We will use focus group interviews to adapt the mental health supports; implement over 3-months; and evaluate impacts on mental health outcomes, feasibility and costs of implementation, utilization and acceptability. We will use validated scales, qualitative interviews, and administrative data. We will develop a framework for adapting and scaling delivery of the mental health supports and a short documentary film highlighting study findings.",2020,2020,University of Ottawa/Université d'Ottawa,150896.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10635,173084,"Mitigating suicide risk during the COVID-19 pandemic via telehealth using an intensive single session of ""Brief Skills for Safer Living""","The COVID-19 pandemic has swiftly increased suicide risk factors including anxiety, depression, isolation, loneliness, job loss and financial stress, as well as intensified a pre-existing lack of access to vital mental health services. The need for widely available resources to reduce risk factors for suicide across all communities is dire. A few studies have demonstrated the effectiveness of single-session in-person interventions for reducing suicide risk. However, these interventions may not adequately target some of the key deficits experienced among those with suicidal risk. To address this need, ""Brief Skills for Safer Living"" (Brief-SfSL), a single-session individual psychotherapy intervention, was developed for the proposed research. Brief-SfSL is adapted from the original SfSL group therapy that has been proven to reduce suicide risk through enhancing personal safety, emotional literacy, coping skills, relationships and problem solving. The proposed study will be the first to test the effectiveness of Brief-SfSL on suicidal ideation at 3 months, which will be delivered by a certified psychotherapist through an online face-to-face meeting in 75 participants with suicide risk. At the Brief-SfSL session, and at virtual follow-up visits 1-week, 1-month and 3-months later, participants will complete questionnaires that measure suicidal ideation, depression, anxiety, social connectedness, life functioning and treatment utilization. This will be the first study of Brief-SfSL in participants with suicide risk. This research will result in rapid improvement in suicide risk over 12 months, which will reduce healthcare utilization on an already over-stretched system. It will also provide evidence for an effective and accessible suicide risk intervention that can be offered rapidly and widely to urban and rural communities during and post-COVID-19 physical distancing restrictions.",2020,2020,Unity Health Toronto,147645,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10636,173085,Preventing Opioid Deaths due to COVID Related Increase in Smoking Illicit Substances (Preventing OD CRISIS),"During the COVID-19 pandemic, British Columbia (BC) has seen a tragic increase in drug overdose deaths, due to a toxic drug supply, people using drugs alone and difficulty accessing harm reduction services. Overdose prevention services (OPS), where people can use drugs in an observed setting, have struggled to meet physical distancing rules, and visits to OPS sites have fallen by 35% since COVID-19 began. At the same time as this recent spike in fatal overdoses, more people have been dying from smoking drugs in BC since 2016. Many people think that their risk of having an overdose is lower if they smoke opioids than if they inject, but this is not actually true. Also, it is more difficult for people who smoke drugs to use OPS, because many sites do not allow smoking, or if they do, have smoking areas outside that are hard for staff to monitor. During COVID-19, there has been a greater drop in people coming to OPS to smoke drugs than to use drugs in other ways, in part because OPS are not set up well to meet the needs of people who smoke. This study will introduce continuous oxygen monitoring at partnering OPS for people who come to smoke opioids or ""down."" We will train peer researchers at these sites to enroll participants, and to gather information from them. While smoking opioids, participants will attach a wrist monitor that will read and transmit their oxygen levels to iPads available to OPS staff. We will train OPS staff to check on participants if their low oxygen levels trigger an alarm. We will examine whether people who smoke drugs and OPS staff find our continuous oxygen monitoring protocol useful. We will also look at how and when oxygen levels change when people smoke opioids. We will use our findings to develop harm reduction messaging for people who smoke drugs, to expand monitoring to other OPS and private locations like supportive housing across BC, and to develop oxygen monitoring apps that allow people who use drugs alone to do so more safely.",2020,2021,B.C. Centre for Disease Control,153000,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10637,173086,For our mental health and psychological well-being in a pandemic period: Partnership for an online implementation of the Recovery College model,"Google Translate: The current pandemic has a clear negative impact on the mental health and well-being of the population, in particular for health workers, on the front line and vulnerable clients. This project aims to evaluate the online adaptation of the training activities of the Health and Recovery Learning Center, Health and Recovery Learning Center French-speaking Canada, in response to the needs of the health community. These settings wish to support the mental health, psychological well-being and resilience of their workers and vulnerable clients (women, people with mental or chronic illness, people with disabilities, family caregivers) by allowing fast, free access. and online has co-learning trainings. Established initially in England, then in 22 countries, the Health and Recovery Learning Center puts forward a unique educational approach where anyone has access to training on well-being and mental health, taking back the power to act and recovery and better living together. The model is based on the sharing of knowledge and the proximity of learners from various backgrounds. By participating in the trainings, learners collectively equip themselves and reflect both on their own way of taking care of themselves as well as on their attitudes, behaviors and practices in matters of mental health. For the past two years, the Sante et Retablissement Learning Center has been funded and managed by a group of 12 partners from different sectors of activity (health and social services, education communities, citizen organizations, academics). Together, they set up the first French-speaking Health and Recovery Learning Center in Canada offering a range of training courses in different cities of Quebec (santeretablissement.com). To date, no training has been offered online and adapted to the needs of healthcare settings in the context of a pandemic.]",2020,2020,Université du Québec à Trois Rivières,150995.7,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Women | Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10638,173087,Adapting and adopting highly specialized pediatric eating disorder treatment to virtual care: Implementation research for the COVID-19 context and beyond,"The negative impact of COVID-19 and the associated social isolation on mental health has been well-described in terms of heightened anxiety and depression. Literature on the impact on individuals with eating disorders (ED) and their families is only just emerging. In most settings across Canada only urgent outpatient medical visits are currently permitted, with ambulatory mental health care having been suspended. Given the success of our previous CIHR-funded implementation work on Family-Based Treatment (FBT) in Ontario, as well as the COVID-19 crisis, an urgent need to adapt FBT to virtual formats and adopt it in our network of ED care providers was identified. We propose to study the implementation of virtual FBT within six programs in our network, building on our previous work, and further developing capacity in our system. Experts in implementation science, community-based research, standard and virtual FBT use/supervision, and EDs have partnered on this implementation project. Using multi-site case study methodology with a mixed method pre/post design we will examine the impact of our implementation approach. We will develop implementation teams at each site, provide a training workshop on vFBT using Zoom Healthcare, and provide ongoing implementation and clinical consultation during the initial implementation of vFBT. Therapists will submit video-recordings of the first four vFBT sessions which will be rated by experts for fidelity. We propose to examine implementation success by studying fidelity to virtual FBT, as well as team and patient/family experience with virtual care, and patient outcomes. Our team is perfectly positioned to respond to this rapid research funding opportunity with an existing network of clinicians who are keen to adopt virtual FBT. Virtual care is not only important in the COVID-19 context but is vital in the North where access to specialized services is extremely limited.",2020,2020,McMaster University,152946.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10639,173088,Socialization Intervention and Mental Health Monitoring for Older Adults in the Era of Physical Distancing due to COVID-19,"Social interactions are a key component to health, and a lack of socialization impacts older adults' physical health, cognitive health, and mental health. COVID-19, physical distancing, and worries about engaging in activities outside of the home due to a highly contagious disease with a high mortality in older adults is creating social isolation and is, therefore, creating an emerging mental health crisis for older adults. A Lancet article published on March 19th 2020 described this emerging crisis and called upon the global community to use technology to help reduce social isolation in the times of COVID-19 induced physical distancing. In this project we are using technology to address social isolation with the aim of promoting mental health for older adults. We are creating virtual socialization hubs, which are a safe spot for older adults to create new friendships and minimize feelings of isolation using videoconferencing software. We are also creating socialization hubs for specialized groups of older adults, including those with lived experience with dementia in collaboration with the Alzheimer Society. Part of creating this safe virtual space and ensuring this intervention is accessible is training older adults how to use this technology, and we have been volunteering to successfully train older adults to use Zoom videoconferencing initially over the telephone since the onset of the pandemic. A second, and equally important virtual intervention, is telephone-based mental health monitoring, where a trained mental health practitioner will use scales monthly to monitor numerous older adults and implement mental health interventions as needed in a timely manner. The monitoring proposed in this project provides screening timely access to mental health resources, addressing the recent call by Galea (2020) for prevention and early detection of the mental health consequences of physical distancing due to COVID-19 for older adults.",2020,2020,University of Saskatchewan,152676.41,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Saskatchewan Health Research Foundation,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2020 +C10640,173089,Responding to dual public health crises in the Emergency Department: Advancing patient-centered care for people who use opioids during COVID-19,"The COVID-19 pandemic has collided with Canada's ongoing overdose emergency to exacerbate harms for people who use opioids. Border closures and travel restrictions are disrupting the illegal drug supply, increasing adulteration and unpredictability. Public health measures to reduce the spread of COVID-19 are creating economic and psychological strain, and physical distancing and health service closures are reducing available supports for people who use opioids. Taken together, these challenges are increasing risk of overdose morbidity and mortality across Canada. Hospital emergency departments are an important setting for reducing opioid-related harm. However, the onset of COVID-19 has resulted in major shifts in how they care for patients. Our research project adopts a mixed method, patient-oriented approach to (1) describe the impacts of COVID-19 on opioid-related emergency department visits; (2) analyze how emergency department care for patients who use opioids has changed during the pandemic; (3) assess emergency department patient and staff perspectives on receiving or providing opioid-related care during COVID-19; and (4) develop training materials and policy and practice recommendations to prepare emergency departments to deliver patient-centred care for people who use opioids during and after COVID-19 and other future crises. Project findings and knowledge translation materials will directly support emergency departments in responding to dual public health emergencies, help ensure equitable healthcare access, and mitigate the combined harms of overdose and COVID-19 for people who use opioids, locally, provincially, and nationally.",2020,2020,Royal Alexandra Hospital,150219.99,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health leadership and governance,2020 +C10641,173090,Supporting the mental health needs of adults with developmental disabilities and their families during COVID-19: A national capacity building project,"Pre-pandemic, adults with developmental disabilities were at increased risk for mental health problems with over forty percent having a psychiatric disorder diagnosis. Limited mental health supports are available to this group and mental health providers are ill equipped to adapt their approach to treating this population. Untreated mental health issues have an impact not only on the people with developmental disabilities but also their family and paid carers. COVID-19 has made the challenges already faced by people with developmental disabilities in accessing and benefiting from mental health services and supports worse. There is an urgent need to address the unique mental health needs of adults with developmental disabilities during COVID-19. To do so requires training for health care and social service providers, families and the individuals themselves. Specifically, each of these groups need tailored resources to help communication of mental health needs; mental health screening; managing depression and anxiety; and resources to assist with caregiver stress. In this one-year study, we will work together with health and social service providers, with families, and with self advocates with developmental disabilities to build their capacity to address mental health issues, focusing on these 4 areas. We will do this by offering 6-week virtual education using a ""hub"" and ""spokes"" model, where participants from across the country can learn together with the centralized experts in the hub. We have already developed the material to be taught and we piloted virtual delivery within Ontario in the first three months of the pandemic. We will test how this works with surveys and interviews. Our team includes people with developmental disabilities, families, and clinicians, as well as scientists, policy makers, and advocacy groups from across the country, who are in strong agreement that we need to be working together to address these urgent mental health concerns.",2020,2020,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,152996.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons | Other,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10642,173091,Evaluation of Archway: A Guided Program for First-Year Student Success and Mental Health and Wellbeing,"First-year students entering postsecondary must navigate a new and complex academic and social environment. Research indicates that this transition is challenging and stressful - academically, emotionally and socially - and can have negative impacts on mental health and wellbeing during what is an important developmental period. Given the COVID-19 pandemic, the incoming 2020 cohort of first-year students will face heightened and new challenges. Most will have spent the conclusion of high school learning virtually while in quarantine in an uncertain and difficult time, to then experience their first year of university living, learning and socializing off-campus, virtually and remotely. In response to COVID-19 and with an appreciation of the considerable stresses students face generally, and particularly in 2020-21 and the potential effects on mental health and well-being, McMaster University has developed an innovative program to support students, entitled Archway. This initiative has been developed to help prevent and intervene early to address common transitional issues for students, which can influence mental health and well-being, aiming to increase: student connectedness (sense of belonging), student supports (opportunities and programs to promote academic success, social-emotional learning and positive health and wellbeing); and student retention (academic success). The current proposal aims to evaluate Archway, to gain a better understanding the transition into first-year for those students who engage and participate in Archway at various levels. The study will not only help to determine the effect of this program for students during COVID-19, but it will help us to better understand the challenges of this transition broadly and to inform future efforts to support students and protect mental health and wellbeing, using virtual and remote platforms and mechanisms to meet the increasingly diverse needs and circumstances of students.",2020,2020,McMaster University,119340,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10643,173092,"Population-based virtual mental health interventions for children, youth and families during COVID-19: If we build it, will they come?","BACKGROUND: Public health emergency measures (EMs) to prevent the spread of COVID-19 have led to losses of structured school time, extracurricular activities, and social activities, impacting all aspects of children's lives. Virtual mental health care (MH) has since become ensconced in our health care system. Despite the anticipated impact on MH and MH care, data examining these outcomes are scarce. Four leading research teams have joined forces to improve our understanding of the MH of Canadian children, youth, and parents and the acceptability of virtual MH interventions during the pandemic within these well characterized clinical and population-based cohorts. GOALS: To determine the impact of COVID-19 related EM on child and parental MH and family functioning in real-time over 12 months. Further, to determine the feasibility of providing MH profile- and developmental age- specific virtual MH interventions to these children and families, identify risk and protective factors, and compare the MH trajectories of vulnerable and otherwise healthy youth throughout the pandemic and into the recovery period. METHODS: 6,200 children ages 0 to 18 years and their families will be recruited for participation. Validated measures will be administered monthly. Feasibility of virtual MH treatment will be determined by measures of recruitment, enrolment, and retention rates for referred interventions. IMPACT: The results of this study will provide the information needed to direct MH care, including virtual care, planning and inform public health discussions regarding the EM reduction process during the pandemic recovery phase and their reimplementation (if necessary) during subsequent COVID-19 pandemic waves.",2020,2020,Hospital for Sick Children,152720.78,Human Populations | Other,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10644,173093,Transdiagnostic internet cognitive-behavior therapy for mixed anxiety and depressive disorders in primary care: A dissemination and implementation study,"Anxiety and depressive disorders are the most common mental disorders in Canada. COVID-19 is expected to put a strain on the already fragile mental health system, as early reports reveal depression and anxiety have been on the rise. Cognitive-behavior therapy (CBT) is the most evidence-based psychotherapy for anxiety and depressive disorders, but it is not widely available in Canada. The ""This Way Up"" virtual clinic in Australia created an innovative internet-based CBT (iCBT) program for mixed anxiety and depressive disorders. We developed a French adaptation of the iCBT program and conducted a feasibility study in Quebec and Ontario to examine the acceptability of the intervention for patients and family physicians. We now propose to conduct a dissemination and implementation study of the iCBT program to support the widespread uptake of this evidence-based intervention in the pandemic context. The study will be carried out in primary care settings in a large health region in Quebec. Participants with anxiety and depressive disorders in primary care will self-refer or be referred by a healthcare provider to iCBT. The implementation and evaluation of iCBT for settings, healthcare providers and patients will be guided by the five dimensions of the RE-AIM framework: reach, effectiveness, adoption, implementation and maintenance. Training sessions will be provided to clinicians to ensure competency in prescribing the program, monitoring patients' progress and symptoms from dashboard, and providing guided support. Quebec healthcare has not yet established a strategy to provide evidence-based iCBT, and this innovation offers a timely and appropriate response to this need. Our project will provide a rapidly accessible low-intensity iCBT intervention in French for anxiety and depression. The program's large-scale implementation could improve the effectiveness, efficiency, equity and access to a proven treatment for common mental disorders.",2020,2020,Université de Sherbrooke,153000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10645,173094,Evaluating the impact of COVID-19 pandemic on primary care using real world data: focus mental health,"The spread of the COVID-19 virus has created havoc in Canada and around the world. Many aspects of all of our lives have been impacted by this pandemic especially the mental health in our populations. Family medicine is the cornerstone of primary care in our healthcare system in Canada. This team multidisciplinary team of investigators will use family physician electronic medical record data or health claims data to measure and evaluate the impact of this pandemic on patients mental health and addictions. In addition, we will compare the mental health impact of this pandemic on our patients in Canada to the experiences in other countries through the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID). INTRePID includes family physician researchers in Australia, Canada, China, Norway, Singapore, South Korea, Sweden, UK and US with access to data on over 85 million patients worldwide.",2020,2020,North York General Hospital,153000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Europe | Western Pacific,,,,Canada,Australia | Canada | China | Norway | Singapore | South Korea | Sweden | United Kingdom | United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10646,173095,"Mental Health, Substance Use, and Service Needs, Access, and Delivery among Two-Spirit, Gay, Bisexual, Queer, and Other Men Who Have Sex with Men in Manitoba","Very little is currently known about the impacts of COVID-19 on the mental health, substance use, and health care access of Two-Spirit, gay, bisexual, queer, and other men who have sex with men (2SGBQM) in Manitoba. We propose a mixed-methods community-based research study to respond to current, pressing knowledge gaps concerning the impacts of the COVID-19 pandemic on 2SGBQM in Manitoba. We will explore the direct and indirect impacts of the pandemic on 2SGBQM (with a focus on marginalized 2SGBQM) in Manitoba, including how COVID-19 impacts their mental health, substance use outcomes, sexual behaviours, and access to healthcare and other services. Our project will investigate the effects of healthcare system transformations and altered service delivery in response to COVID-19 on both service providers and the 2SGBQM receiving addictions/substance use and mental health care in Manitoba. To accomplish these objectives, we will first use an online survey to gather data on demographics, health and social disparities, and impacts of COVID-19 on mental health, substance use, and healthcare/service access among a sample of 2SGBQM (n=350) in Manitoba. Next, we will conduct interviews with 2SGBQM (n=30) and service providers (n=10) to offer a more contextualized understanding of the survey findings. We will initiate a training program called 'Investigaytors' within this study to provide an integrated approach to knowledge translation and exchange on this project, and to build capacity among young 2SGBQM leaders in Manitoba. Our proposed research will be the first study of COVID-19 impacts among 2SGBQM in a Prairie province. The data from this study will contribute important new information regarding the impacts of COVID-19 on 2SGBQM, and inform pandemic intervention preparedness in Manitoba. This study will also inform mental health and substance use/harm reduction services, enhance mental health assessments, and improve virtual healthcare delivery for 2SGBQM in Manitoba.",2020,2020,University of Manitoba,133875,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Policies for public health, disease control & community resilience",Indirect health impacts | Health service delivery | Community engagement,2020 +C10647,"173096, 175555",Predicting the risk of developing mental and substance use disorders due to COVID-19: machine learning applied to health service utilization data to facilitate access to effective treatments. [Added supplement: COVID-19 Variant Supplement],"COVID-19 has caused unprecedented demand on health care systems worldwide. Early indications suggest that the pandemic will lead to a surge in mental health and substance use disorders. This study aims to examine these mental and substance use implications through comparison of patient cohorts in BC, Canada based on their ""illness dose"" of COVID-19. In partnership with the Health Authorities and the BC Ministry of Health, we will deploy an online survey to assess these patient groups to detect the new onset or worsening of mental and substance use disorders that may be attributed to COVID-19. We will leverage Population Data BC, one of the world's largest collections of health services data containing individual-level, de-identified longitudinal data on BC's 4.7 million residents. We will link our survey results with data available at Population BC data, in order to retrospectively study the sociodemographic, service utilization, prescription drug use, employment, and environmental exposures of patients over the past 10 years. Using machine learning methods (Artificial Intelligence) to compare these different cohorts, each of which represents different ""doses"" of exposure to COVID-19, we will identify patients that are at increased risk of developing COVID-19-related adverse mental health outcomes. We will follow up with COVID-19 positive patients through a virtual clinic and assess existing treatment options for mental and substance use problems. Ultimately, we will have a system to predict increased risk of neuropsychiatric impact of COVID-19 on patients in BC, and to facilitate access of these patients early on to existing mental health services. This important data will allow Health Authorities to prepare for subsequent waves of COVID-19 with the tools required to rapidly mitigate its adverse effects on mental health and substance use.",2020,2022,University of British Columbia,192392.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10648,173097,Keeping Complex Chronic Pain Patients Alive During and After the COVID-19 Pandemic,"Chronic pain affects nearly 20% of Canadians, and sixty percent or more of individuals with chronic pain are also struggling with mental health or substance use disorders (referred to as complex chronic pain, or CCP, patients). This is a major concern in the best of times and has become an emergency during the COVID-19 pandemic. Now individuals suffering from chronic pain are faced with the additional challenges of quarantine, including the stress of isolation, delays in much needed medical care, and anxiety of possible infection to self or loved ones. Prior to COVID-19, psychologists at The Transitional Pain Service and the GoodHope Ehlers-Danlos Syndrome Clinic at Toronto General Hospital have adapted gold standard treatments for mental health and substance use for the unique needs of individuals with CCP. We propose to develop these treatments into a virtual intervention that will meet the needs of patients during and after the COVID-19 pandemic. We will use a mobile health application (called Manage My Pain or MMP) already in use by our patients to identify patients with CCP currently struggling with mental health issues or at risk of opioid misuse. With CIHR support, we will be able to offer treatment to these vulnerable patients throughout Ontario and Alberta from Toronto General Hospital and our partner sites at the Opioid Deprescribing Program in Calgary and the Centenary Pain Clinic in Toronto. We will also help patients with chronic pain across the country access these treatments by creating an educational website with self-help materials and information for providers. This project will provide much needed mental health care to thousands of Canadians during this crisis and will develop the infrastructure to ensure greater availability of high quality psychological care for patients with chronic pain once the crisis has passed.",2020,2020,University Health Network,152195.99,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10649,173098,"Expanding a Randomized Controlled Trial of a Couple Internet-Delivered PTSD Intervention to Reach Military Members, Veterans, and First Responders with COVID-19-Related Trauma Exposure","Posttraumatic Stress Disorder (PTSD) will be a severe problem in Canada in the wake of COVID-19, especially for Military Members, Veterans, First Responders, and Healthcare Workers (MVFH). However, gold standard face-to-face PTSD treatments do not meet current MVFH needs, which requires virtual interventions and minimal healthcare resources. Recognizing the need for a virtual, low-resource PTSD intervention for MVFH with PTSD and their loved ones, our team developed Couple HOPES (Helping Overcome PTSD and Enhance Satisfaction). Couple HOPES is a secure, online self-help intervention for those with PTSD and their partners (www.couplehopes.com). Our team has already received funding to test if Couple HOPES improves PTSD symptoms, relationship satisfaction, and related outcomes more than a waitlist condition in 70 couples with one member who is a MVFH with PTSD related to any kind of trauma exposure. However, MVFH are now particularly likely to be exposed to traumas related to COVID-19. It is essential to identify if Couple HOPES is safe and helpful for couples involving MVFH with COVID-19-related PTSD specifically. This project will expand our existing RCT to recruit an additional 70 couples wherein one member is a MVFH with COVID-19-related PTSD. We will examine if Couple HOPES is helpful in improving PTSD symptoms and relationship satisfaction for such couples, and if it is more or less helpful to this end for these couples compared to those with other forms of trauma exposure. 140 couples including a MVFH with PTSD, half of which have PTSD as a result of a COVID-19-related trauma, will be randomly assigned to receive Couple HOPES or to a waitlist. PTSD symptoms and relationship satisfaction will be measured ~weekly during the intervention and one month after it. Related problems (e.g., depression, anxiety, healthcare use) will be measured before, in the middle of, after, and one month after, the intervention.",2020,2021,York University,153000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Emergency Responders | Military Personnel | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10650,"173099, 175554",A behavioural science approach to evaluate the prevalence and predictors of COVID-19-related mental health issues and maladaptive behavioural coping (MBC) to inform the development of strategies for tailored interventions [Added supplement: COVID-19 Variant Supplement],"COVID-19 will lead to an increase in mental health issues (e.g., depression, anxiety, post-traumatic stress disorder) and maladaptive behavioural coping (e.g., drinking alcohol, taking drugs, taking out our frustrations on loved ones). However, not everyone will be affected or affected in the same way. In order to ensure that the eight people are getting the services they need, we need to understand what kinds of mental health and maladaptive behavioural coping problems are occurring, who they are occurring in, and how best to engage these individuals in the care that is available. The proposed project will be an 'add-on' to an ongoing Canadian-led large international online study looking at the impacts of COVID-19 (The iCARE study: www.mbmc-cmcm.ca/covid19). It will see how people are feeling and coping with COVID-19, in a diverse group of Canadians (men, women, young, old) - using representative sampling, over the next several months. The 'mental health and maladaptive behavioural coping' module will be completed with the main iCARE survey 5 times between July 2020 and January 2021 (a total of 15,000 responses). The questions in the module were developed using behavioural science theory and are similar to those being used in other international studies, meaning that what is happening in Canada can be compared to what is happening in other countries. This project will provide information on the 'real-time' impacts of COVID-19 on mental health and how people are coping among Canadians over the coming months. More importantly, we will be able to understand who is most at risk, what kinds of support, treatments and services they need, and how best to engage them in the available services. This information will be passed on to the federal and provincial governments to help them develop better strategies to ""flatten the mental health curve"" and improve quality of life outcomes in Canadians negatively impacted by COVID-19.",2020,2022,CIUSSS du Nord de l'Ile de Montréal Hôpital Sacré Coeur,186180,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10651,173100,"Development, implementation, and evaluation of equitable and effective e-mental health care delivery for parents and care givers struggling with anxiety and depression arising during the COVID-19 pandemic: improving access and matching services to need.","Parents, particularly women, are experiencing heightened anxiety and depression during the COVID-19 pandemic. It is unclear which specific stressors faced by parents are overwhelming their coping resources during COVID-19. Evidently though, treatment is needed. E-mental health care has become a necessity during the pandemic. Not all adult e-services, however, provide the necessary content to help parents with pandemic-related distress and needs nor provide options to access care in a way that is flexible to the needs of parents with children at home. To address this problem, we adapted an existing iCBT for anxiety and depression program in an innovative way by integrating COVID-19-specific content and developing three service delivery options: unguided, minimally guided, or fully guided. The present study seeks to: (1) investigate parents' preferences for levels of iCBT service delivery in the context of COVID-19, (2) match access to service with parents' individual needs by enrolling them in a COVID-19-adapted iCBT program with their choice of service delivery method and explore whether levels of iCBT service delivery predict treatment outcome; (3) identify which COVID-19 parent stressors are most prevalent and associated with intervention outcome (by gender), by using machine learning to mine written responses in the iCBT program; and (4) improve rapid access to e-mental health through primary care and mental health and addictions services. Participants will be parents (of children under 18 years) recruited from primary care and mental health and addictions services in the Maritimes. They will choose unguided, minimally-guided or fully-guided iCBT. Guidance will be via phone, video, or in-app messaging (at participant preference) at a time convenient for the parent. Outcomes will be measured pre- and post-intervention. Results will contribute to the development of equitable and effective mental health services for parents, particularly during a pandemic.",2020,2020,University of New Brunswick,148942.44,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | NBHRF,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10652,173101,Promising Practices in Accessing Virtual Mental Health: Supporting Refugees during COVID-19,"The goal of this project is to identify key concerns and promising practices with respect to delivery of virtual mental health services, and to develop guidelines for referring refugee clients to these services. The COVID pandemic can affect immigrant and refugee mental health in multiple ways: 1) anxiety about the illness itself; 2) challenges due public health measures, including social isolation, and one's ability to enact these measures; 3) economic stress due to loss or reduction of employment; and 4) decreased or altered access to mental health treatments and medications for those already receiving services. While many on-line mental health services have become available or expanded services, new questions are arising in the settlement sector around access and barriers to these services and considerations when referring. Immigrants may find access to linguistically and culturally appropriate virtual mental health services difficult to find and navigate. Refugees may face even greater barriers relative to other immigrants. Vulnerable populations such as refugees are more likely to be living in crowded conditions that can make physical distancing difficult and may have greater difficulty accessing or understanding public health directives; they are more likely to be experiencing economic hardship; and they may be less likely to have access to or be comfortable using virtual technologies. Through interviews with settlement workers, refugee newcomers, mental health practitioners and virtual mental health experts, we will develop guidelines around WHEN to refer WHICH clients to WHICH virtual mental health services; HOW to refer and document virtual mental health services; and WHAT are key considerations in referring and recommending virtual mental health services to refugee clients. Although developed for refugees, these recommendations will highlight barriers faced by many vulnerable populations and sharing promising practices will support better access for all.",2020,2020,York University,120916.67,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10653,173102,An examination of the impact of COVID-19 on the mental health of Canadian medical residents,"Physicians working on the frontlines during the COVID-19 pandemic are at high risk of experiencing burnout, depression, anxiety, and trauma. Burnout, experienced by more than 50% of medical trainees and practicing physicians under usual conditions, is a public health crisis that compromises patient safety through the provision of poorer quality of care. While initial studies have reported significant distress among healthcare workers exposed to COVID-19, few have examined medical trainees specifically, highlighting an important gap. As the pandemic has progressed in Canada, medical residents (trainee physicians) have expressed new concerns about practicing outside their scope, protecting their families, and fear for their personal safety. This study will use a novel approach to understand the mental health service needs of individuals undergoing medical residency during the pandemic and inform delivery of appropriate mitigation strategies. Using a comprehensive online survey we aim to better identify predictive factors associated with emergence of mental health symptoms in Canadian medical residents during the pandemic. We will apply an innovative artificial intelligence (AI)-based social media algorithm to retrospectively track mood and psychological distress status from residents' social media posts to identify periods of worsening mental health. Finally, we will conduct qualitative interviews to permit in-depth exploration of mental health service use during the pandemic and perspectives on resident satisfaction with available services. We will examine all data through a sex and gender-based lens, as various biological and socio-cultural factors may be differentially associated with susceptibility and resilience to mental illness among residents. Findings will reveal the impact of the pandemic on medical resident mental health and its implications for Canadian medical education while informing service needs to minimize its effects on cohorts of new physicians.",2020,2020,University of Ottawa Institute of Mental Health Research/Institut de recherche en santé mentale de l'Université d'Ottawa,77678.1,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10654,"173103, 175513",Screening Student Resiliency and Mental Health Indicators During School Re-Entry [Added supplement: COVID-19 Variant Supplement],"COVID-19 displaced millions of students from their schools, teachers, and peer groups. Early data proclaimed everything from a second ""mental health pandemic"" wave to significant expressions of strength and resilience. The primary research question is: What are the self-reported mental health needs and resiliency indicators of students returning to school amidst COVID-19? This information is urgently needed by schools to ensure effective, appropriate, and time sensitive mental health supports are available to returning learners in their metropolitan schools (Catholic and public) in two major Canadian cities. This study will measure behavioural and mental health functioning and resilience in a large sample (N approx. 3000) of metropolitan school district students at the time of school re-entry and again at 3, 6, and 9 months post school re-entry. Students will complete measures of COVID-19 health behaviours, mental health symptoms and adaptive behaviours, and resiliency. Results will inform strategic planning related to student services for these school districts and assist in the development of system-wide intervention and resource allocation for students returning to school in Fall, 2020. Knowledge translation activities will include dissemination of results to the metro school districts via reports, data webinars, infographics, social media platforms, and peer-reviewed publications. In summary, the present study will assist four major metro school districts to gather screening data useful for prioritizing district-wide initiatives that can inform strategies to build on identified strengths and remediate self-reported learning, behavioural, and social-emotional needs of students upon school re-entry.",2020,2022,University of Calgary,191801.56,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10655,173104,A cohort study of Covid-19 test positive and negative patients to detect and provide early treatment for mental health disorders,"There has been ample speculation about how the COVID-19 pandemic and lockdown may affect mental health. This proposal aims to screen patients who have been infected with Covid-19 to see how many experience symptoms of mental illness 1 year after testing compared to individuals who tested negative. Participants will complete measures of depression, anxiety, post-traumatic stress disorder, quality of life, and cognitive skills. They will complete these assessments at 6, 9 and 12 months after their first test. Using this study, we hope to better understand the prevalence and nature of mental illness that occurs during and after this global pandemic. Results from this study will also provide information for prevention, screening programmes and service delivery for mental health disorders during COVID-19 so that access can be matched to highest needs",2020,2020,Ottawa Hospital Research Institute/Institut de recherche de l'Hôpital d'Ottawa,152729.19,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10656,173105,Traumatic stress and Mental Health Impacts of the COVID-19 Pandemic on Front-Line Workers in Homeless Services,"Lay Abstract: This proposal addresses the mental health impacts of the COVID-19 pandemic on frontline workers in the homeless sector. Prior to the COVID-19 pandemic outbreak, our research reported high levels of direct traumatic stress among frontline workers. In five previous studies, we surveyed frontline workers in homeless services, in Calgary, Edmonton, AB, and Saint John, NB. Results showed consistently high rates of traumatic stress across all locations, exacerbated by lack of training, inadequate preparation for responses in a pandemic and a perceived lack of physical and psychological safety that could potentiate further primary traumatic stress. Given the sudden and protracted impact of the COVID-19 virus and the systemic challenges faced in the social services, it is critical to examine how these experiences are impacting frontline workers' mental health and well-being. The overall goal of this research is to document the extent to which the COVID-19 crisis has impacted psychological well-being and work-related disability among frontline workers in the homeless sector. A second aim is to document rates of disability (stress) leave for staff through Workers' Compensation Board claims to further asses the extent of this impact. Finally, we will extend the study to four other Canadian cities. Together this data will present important information on staff stress, the impact of the COVID-19 virus, resultant disabilities, and possible mitigating factors resulting from organizational changes. Thus, this study would provide understanding of the pandemic's impact on this vital workforce and illuminate any organizational actions that informed mitigating strategies for staff well-being. This is especially critical as health authorities predict a second and possible third wave of infections that would seriously deplete an already highly stressed group of essential workers.",2020,2020,University of Calgary,151130.34,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | NBHRF,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C10657,173106,Mental health planning in the era of a pandemic: appropriately matching mental health needs with resources across Canada through a rapid assessment of COVID-19's impact on adults and older adults.,"This timely study is a unique opportunity to assess the impact of COVID-19 on depression, anxiety and post-traumatic stress rates and health service use in adults and older adults across Canada and estimate their health needs and impact on future health services and related health system costs. This evidence will inform Canada-wide and province specific strategic planning for the allocation of human and financial resources to offer quality mental health services that will meet the mental health needs of adults and older adults; highlight at-risk groups to inform recommendations on tailored mental health strategies and additional resources required post-pandemic; and provide a comprehensive baseline portrait of mental health status and needs during the pandemic to prepare for Canada's mental health response to future outbreaks.",2020,2020,Université de Sherbrooke,153000,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10658,173107,Protecting and improving the mental health of physicians during and after the COVID-19 pandemic,"Canadian physicians have faced a number of challenges to their mental health and wellbeing during the COVID-19 pandemic. Many are on the front lines treating patients sick with COVID-19, others have had to rapidly adapt to continue delivering routine care, and like many Canadians some have lost jobs or face reduced income from the cancellation or operations and clinics. In addition, many physicians were already at risk of poor mental health prior to the pandemic with national surveys showing high rates of depression and burnout. Taken together, there is reason to be concerned that COVID-19 may result in worsening mental health for Canadian physicians. There are three objectives of this research project: First, to examine in general how the mental health of physicians has been impacted by COVID-19; Second, to identify the characteristics of physicians whose mental health has decreased during the pandemic; Third, to determine if physicians impacted by COVID-19 are receiving the mental health services they require. To complete each of our objectives, we will use a word leading innovative database that links a registry of all physicians who have a license to practice medicine in Ontario (more than 50,000 physicians) to their own health care use and their health outcomes. We will specifically look at how health care visits - including emergency department visits, hospitalizations and outpatient visits to psychiatrists and family physicians - related to depression, anxiety, suicidal behaviour, and harmful substance use (e.g. alcohol, opioids, illicit drugs) have changed during and after the pandemic. We have partnered with physician wellness groups and physician organizations across Canada - including the Ontario Medical Association and the Canadian Medical Association - who plan to use information generated from this project to improve delivery of mental health services and advocate for policies that support the resilience and well-being of the physician work force.",2020,2020,Ottawa Hospital Research Institute/Institut de recherche de l'Hôpital d'Ottawa,152855.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10659,173108,Advancing Digital Connectivity to Support Population Mental Health during COVID-19,"COVID-19 has created multiple mental health stressors as identified by the World Health Organization. Canadians are being overwhelmed with rapid changes and uncertainty contributing to the mental health burden of pandemic life. This study will build on a previous knowledge synthesis project exploring existing and emerging digital mental health interventions to support better access to these resources during COVID-19. The use of a lower-tech two-way SMS texting program will provide opportunity for real-time community engagement (polling), to assess mental health needs and barriers to digital intervention access. The RE-AIM framework, a well-established implementation tool for planning and evaluating public health initiatives, will be used to monitor the Reach, Effectiveness, Adoption, Implementation, and Maintenance of the program through three phases in a mixed methods design. The following research objectives will guide these efforts: 1) Implement a mental health COVID-19 SMS in collaboration with a patient/community advisory group to enhance the reach of the initiative; 2) Advance the effectiveness of the texting service through iterative cycles of reflection and action driven by advisory and SMS participant input; and, 3) Evaluate the adoption of the COVID-19 SMS program with a focus on acceptability, satisfaction, and clinical benefit. The use of texting extends the reach of this digital intervention across divides that may separate some vulnerable or disadvantaged groups from other forms of mental health access and the flexibility of the implementation approach allows for rapid adaptability as the pandemic unfolds.",2020,2020,University of Saskatchewan,149547.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Saskatchewan Health Research Foundation,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10660,173109,"Psychological well-being of housekeeping staff in Canadian hospitals, determining factors and influencing conditions in times of pandemic (COVID-19).","Google Translate: Housekeeping staff in hospitals are on the front line in the fight against COVID-19, but too little is said about it. These people expose themselves, put themselves at risk and work tirelessly to ensure the safety of all patients but also of all hospital staff. They carry a heavy responsibility and experience high psychological stress. Our team of researchers wants to measure the psychological distress of housekeeping workers during COVID-19 but also to collect information on what promotes this distress (personal, organizational, or other factors). We will therefore interview housekeeping workers in several Canadian hospitals by electronic survey, and we will meet with groups of workers to discuss with them to fully understand their concerns.In addition we will conduct interviews with key people such as managers. , or union representatives to discuss strategies to be put in place at the establishment level to prevent the occurrence of this psychological stress. Better understanding what determines the psychological distress of housekeeping workers will help educate health care facilities to better prevent this distress by modifying their processes. With simple tools to identify this distress, health establishments will also be able to periodically monitor the psychological health of their household maintenance staff and offer them the appropriate services at all times, even away from COVID-19.]",2020,2020,University of Ottawa/Université d'Ottawa,152256.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10661,173110,Assessing the Capacity of the Mental Health and Substance Use Workforce to Respond to COVID-19,"BACKGROUND: The people who provide mental health and substance use services play acritical role in the response to COVID-19.The pandemic has brought about big changes for this workforce, such as the sudden shift to online approaches, adjusting to wearing masks, and responding to increasing levels of anxiety, trauma and grief in the population. We know from previous disasters and epidemics that the mental health and substance use impacts are likely to be complex and long-lasting, and may not fully emerge until after the worst of the crisis. PURPOSE: This study will provide better information about the availability of mental health professionals like psychologists, social workers and addictions counsellors to respond to the mental health and substance use needs of people in response to COVID-19. GOALS: The specific goals are to address gaps in information about how COVID-19 has changed the kinds of mental and substance use services that people need and that can be offered, and to provide the people who make decisions about mental health and substances use services with the information they need to improve these services. APPROACH: We will summarize information that has been previously published and we will gather new information from surveys, interviews with experts and mental health and substance use service providers and their organizations. We will examine not only those working in the public system, but also in the private system including employee assistance programs, private practitioners and those in private treatment centres. Once all of this information is gathered, we will engage with leaders and decision makers to build a shared action plan for next steps.",2020,2020,University of Ottawa/Université d'Ottawa,141149.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health leadership and governance,2020 +C10662,173111,Opioid Use Disorder Care during COVID-19 Disruptions,"COVID-19 is disrupting opioid use disorder treatment, and the impacts of these disruptions are unknown. Community addictions clinics have switched to virtual care, decreased their opening hours, or closed. At the same time, opioid overdoses in Alberta and British Columbia have increased. It is currently not known whether patients are being supported through adjusted opioid use disorder care, or whether they are going undertreated. This project will combine review of opioid addiction clinic and emergency department data to profile the impact of COVID-19 on opioid use disorder treatment. Crucially, we will assess impacts of changes in opioid use disorder treatment for First Nations members, in partnership with the Blackfoot Confederacy.",2020,2021,University of Alberta,152851.59,Human Populations | Other,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10663,173112,Substance use disorder treatment transformations due to the COVID-19 pandemic: Impact on Indigenous patients and communities,"The COVID-19 pandemic has had a serious impact on Indigenous Peoples across Canada. One area of concern pertains to the disruption of substance use treatment and recovery. Indigenous Nations have rapidly transformed services to expand access through telemedicine and greater access to medications. This study seeks to evaluate the impact of the pandemic on substance use treatment among Indigenous Peoples, including challenges and successes with these rapid service transformations. We also seek to understand the pandemic's impact on access to culturally-safe treatment, including access to Indigenous traditional healing practices. The study conception stems from the Indigenous Working Group (IWG) of the Quebec-Atlantic Node of the Canadian Research Initiative in Substance Misuse. The study will be a partnership with 6 Indigenous organizations affiliated with the IWG. Qualitative interviews and talking circles (via video-conferencing technology, as necessary) with key stakeholders, clinicians, patients, and community members will be conducted in order to understand experiences and necessary resources in the context of the pandemic and rapid service transformations. Questions will pertain to patients' response to the pandemic, barriers to treatment, complexities with the transition to telemedicine, challenges with accessing traditional healing, and strategies for expanding treatment access and promoting recovery. We anticipate documenting promising practices for expanding treatment access permanently, not only during the pandemic (given the limited treatment access many Indigenous communities have). The study will be guided by a Two-Eyed Seeing framework, and all research will be conducted in consultation with an Indigenous research advisory council. Data will be analyzed using principles of thematic content analysis. Knowledge from this study will be disseminated to Indigenous Nations and organizations across Canada, as well as to federal and provincial agencies.",2020,2021,McGill University/Université McGill,127849.86,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | NBHRF,Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C10664,173113,Assessing mental health and substance use needs and service disruptions for people released from custody during the COVID-19 pandemic.,"Even at the best of times, people who are released from correctional facilities face significant mental health and addiction challenges, in addition to poverty, homelessness, poor physical health, and discrimination as they return to the community. The COVID-19 pandemic has made the community reentry process, including access to mental health and substance use services, more difficult for releasees. Particularly affected are Indigenous, Black and 2SLGBTQ persons, who are over-represented in the prison system. Through qualitative interviews this study will examine the mental health and substance use challenges of community reentry for people released from custody during the pandemic. Within the Greater Toronto Area, we will explore how this population is adapting to disruptions to mental health and addiction services and how service agencies are adapting their practices to support the population despite physical distancing and other public health safety measures. We propose a rapid 3-cycle evaluation of service disruptions/adaptations and releasees needs and responses to service changes followed by in-depth qualitative analysis. The study is a collaboration of researchers and community service providers and knowledge users who support people who face incarceration. The findings will inform government responses to pandemics to ensure people who have incarceration histories are adequately supported. In addition, the findings will document innovative adaptations within the mental health and addiction sectors that can inform the present and future pandemic plans, preparations, and responses to better address the needs of this population.",2020,2021,Unity Health Toronto,153000,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10665,173114,The First Nations Wellness Initiative: A Community-Driven Approach to Promoting Mental Wellness in the Context of the COVID-19 Pandemic,"Despite high rates of mental health and substance use (MHS) challenges in many First Nations due to the effects of colonialism, many existing programs designed to address these challenges are not culturally safe, wholistic or responsive to community-specific needs. The COVID-19 pandemic is exacerbating these MHS challenges and First Nations communities are disproportionately affected, largely due to health and socio-economic disparities stemming from the enduring effects of colonialism. The need for community-driven strength-based mental wellness strategies is more urgent than ever. The First Nations Wellness Initiative (FNWI) is a collaborative model for developing community-driven, evidence-informed and community-based wellness strategies addressing age- and gender-specific MHS challenges in First Nations communities. The project aims to mitigate the impacts of the pandemic in two First Nations by implementing and enhancing the FNWI. Building on strong research partnerships with two First Nations, we will develop sustainable mental wellness strategies in both communities and disseminate knowledge to promote successful wellness strategies in other First Nations. Participatory Action Research will be used to develop strategies that are strengths based, culturally appropriate, built around community needs, and informed by previously collected qualitative and quantitative data. Wellness promotion, prevention of MHS challenges, and community and individual interventions will use community-driven methods that are informed by local data and draw on strengths and resilience resources within the communities. The team will evaluate the strategies and their outcomes and disseminate best practice knowledge from the strategies regionally, provincially and nationally. This collaborative community-driven research-to-action initiative will result in sustainable, culturally safe and wholistic wellness strategies developed by and for First Nations during the current pandemic.",2020,2021,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,153000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | MOH,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Community engagement,2020 +C10666,173115,"Nothing without us: Towards inclusive, equitable COVID-19 policy responses for youth with disabilities and their families","Persons with disabilities and their caregivers are an at-risk population in the COVID-19 pandemic who's mental health has been disproportionately impacted by the policy measures adopted in response. Given the increased risk for this vulnerable population during the pandemic and existing higher rates of mental health concerns, policy and services that are not designed to meet the needs of people with disabilities and their families in emergency pandemic preparedness efforts can add to or create mental health concerns. Addressing these risks in the spirit of ""Nothing Without Us"" and the Accessible Canada Act, and in recognition of Canada's domestic and international human rights obligations is critical. Unfortunately, there is inadequate data collection and insufficient emergency preparedness planning and response for people with disabilities. The goal of this project is to identify policy responses established during the COVID-19 outbreak in Canada and internationally that promote resilience and address mental health challenges and needs of youth with disabilities and their families. To achieve this we will: 1) monitor and compare how COVID-19 policy measures adopted across provinces in Canada align with the provisions of the United Nations Convention on the Rights of Persons with Disabilities (UN CRPD), the Sendai Framework for Disaster Risk Reduction; and the WHO's disability-specific recommendations issued during the COVID19 outbreak; 2) analyze experiences with COVID-19 policies through interviews with youth with disability and their caregivers; 3) integrate findings to co-design and mobilize policy recommendations with partners. Findings are critical to provide evidence to inform decision- making and planning that mitigate potential mental health harms and promote equity in COVID-19 policymaking. Findings will generate knowledge to enhance disability inclusion in future public health emergencies being implemented for youth with disability and their caregivers.",2020,2021,University of Calgary,152732.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Disabled persons,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Policies for public health, disease control & community resilience",Indirect health impacts | Health leadership and governance | Community engagement,2020 +C10667,173202,Characterization of Cellular and Humoral Immunity Against SARS-CoV-2,"Understanding the role of the immune response against SARS-CoV-2 in recovery from infection is critical for identifying people who have been exposed to SARS-CoV-2 and for determining whether the immune response confers protection against future infection. It is also critical for design and development of effective vaccines and immune-based treatments against SARS-CoV-2. We plan to systematically assess the strength, specificity, nature and durability of antibody and cellular immune responses generated against SARS-CoV-2 in relation to severity of infection. To do this, we will recruit individuals deemed to have recovered from SARS-CoV-2 infection and additionally test their close contacts to identify individuals who had very mild or asymptomatic SARS-CoV-2 infection. With blood samples obtained from these subjects and from persons hospitalized for SARS-CoV-2 infection, we will test and compare how their antibodies and immune cells interact with SARS-CoV-2 proteins how these interactions affect SARS-CoV-2 in cell culture and how these interactions change over time. These experiments should identify parts of the virus targeted by successful immune responses, parts of the virus targeted by detrimental immune responses and the strength required of successful immune responses. Analysis of these data will help guide vaccine design and evaluation. Testing the ability of antibodies from recovered persons to inhibit SARS-CoV-2 growth in cell culture will provide criteria for identifying the best candidates for donation of convalescent plasma to treat SARS-CoV-2-infected persons with severe disease.",2020,2021,Memorial University of Newfoundland,380338.88,Human Populations,Unspecified,Unspecified,,Unspecified,Unspecified,,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C10668,"173203, 175561",Early immune predictors of sustained SARS-CoV-2 antibody responses after COVID-19 disease [Added supplement: COVID-19 Variant Supplement],"COVID-19, a disease caused by a new Coronavirus, is an unprecedented global health crisis for which we currently have nor safe nor rapid response. Given the absence of vaccines and effective therapies, it is essential to understand the development, effectiveness and maintenance of antiviral responses against its causing agent, the SARS-CoV-2 virus. The highly variable immune response against SARS-CoV-2 define the severity of the disease, but many critical questions remain: 1) can we predict patients that will experience a severe disease and delayed viral clearance? 2) do survivors of COVID-19 develop durable and protective antiviral immunity? 3) can serology identify convalescent COVID-19 patients who are at high risk of re-infection? 4) does re-exposure to the virus boost their antiviral immunity? We propose the creation of a multi-site consortium composed of 12 scientists (6 women and 6 men) with solid expertise in virology and immunology and from leading academic institutions in Quebec (UdeM, IRCM) and the US (Columbia, NY) to study antiviral immunity in COVID-19 in both sexes to address unresolved issues, as outlined in the CIHR call: in Aim 1 and 2, we focus on early clinical and immunological features of COVID-19 that can predict the emergence of protective and durable antibodies. We will compare cohorts of patients enrolled in the ""Biobanque quebecoise de la COVID-19"" (BQC19) that experienced mild or severe COVID-19 or COVID-19-like symptoms attributed to another infectious agent. In Aim 3, we will focus on a cohort of health care worker tending COVID-19 patients, therefore at higher risk of repeat exposure to the virus. Using this cohort, we will study the effect of repeat exposure on immunity boosting against the virus and help define the immunological requirements of a successful vaccine. Taken together, our proposal will provide the immunological perspective needed to better prepare and implement a safe exit from the current public health crisis.",2020,2022,Centre hospitalier de l'Université de Montréal,841193.23,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +C10669,173204,Long-term protective immunity against SARS-CoV-2 virus in COVID-19 patients,"The current COVID-19 pandemic is caused by a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current tests are unable to accurately identify patients who are infected or determine the effectiveness of their immune response against the virus. They also cannot identify patients who have produced a protective immune response for combating future re-infection with SARS-CoV-2. There are many question regarding the effects this pandemic has presented our society; however, understanding if individuals are protected against the virus, after being infected, continues to be very important. In this proposal, we will identify how our bodies react to the virus by examining antibodies in the immune system and by studying the memory immune cells that produce antibodies to determine if and how long our bodies are protected against the virus in the future. We will do this by identifying which patients have developed an immune response (antibodies) and then test for their ability to eliminate the SARS-CoV-2 virus, effectively. We will also determine if recovered COVID-19 patients develop memory immune cells capable of fighting re-infections in the future. These tests are important for many reasons, including: 1) accurately diagnose COVID-19 patients by identifying who developed an immune response; 2) identify individuals who mounted strong antibody responses that eliminates the SARS-CoV-2 virus and 3) determine if there is immune memory against COVID-19 that could protect against re-infection. A deeper understanding of the immune response will help fight the current COVID-19 pandemic and better prepare us for future pandemics.",2020,2021,McMaster University,267750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C10670,173205,Simple assay to assess antibody-dependent enhancement of SARS-CoV-2,"Antibodies are one of our main immune defences against invading pathogens. However, for some viruses, under certain conditions, antibodies can provide a means for enhanced virus entry and replication in a number of cell types. This phenomenon, known as antibody-dependent enhancement (ADE), often exacerbates disease and is a major challenge for prevention of viral disease by vaccination. ADE has been demonstrated for several human and animal coronaviruses, so there is concern that ADE may increase COVID-19 disease during natural infection or following vaccination. The goal of this proposal is to develop a test for human serum samples that will detect ADE of SARS-CoV-2, the virus that causes COVID-19. This assay will be relatively simple to perform and will allow high-throughput screening of human serum samples in clinical laboratories. It will allow physicians and scientists to assess whether antibodies produced in response to natural infection or vaccination may predispose an individual to ADE, and potentially more severe disease. In addition, to better understand the importance of ADE in SARS-CoV-2 infection, we will further investigate this phenomenon in biologically-relevant circulating human immune cells.",2020,2021,Western University,115553.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +C10671,"173206, 175501","A low-cost, portable, and decentralized microfluidic device for detecting SARS-CoV-2 neutralizing antibodies [Added supplement: COVID-19 Variant Supplement]","Serological surveillance provides population-wide immunity status in a timely manner, which is important evidence in directing public health policy during the COVID-19 pandemic. Immunoassays are serological tests that can measure antibody levels to an infectious disease, and are being rapidly employed to identify individuals with potential immunity to SARS-CoV-2. Although immunoassays can quantify antibodies in a sample, they do not directly measure neutralizing antibodies (nAbs). Tests currently available for nAbs are expensive, labour intensive, require high biosafety containment, and are can only be preformed in centralized national laboratories. Low-cost, rapid, decentralized testing for SARS-CoV-2 nAbs will expedite serological surveys and help evaluate herd immunity and vaccine effectiveness. The goal of this project is to develop a fast and cost-effective assay to detect nAbs for SARS-CoV-2 and with reduced biosafety requirements for immediate distribution. This assay will then be integrated into a paper-based microfluidic device for portable testing that uses a one-step assay capable of separating out antibodies from whole blood. The development of new diagnostic tools will be critical for serological surveillance during and after the current COVID-19 pandemic and can help direct Canada's response to prevent further outbreaks. Low-cost and portable serological testing will also enable low- and middle-income countries to perform high-quality serological surveys and these tools will be of immense value to displaced populations (i.e. refugees). Furthermore, rapid and reliable screening of plasma samples for neutralizing antibodies will provide a valuable resource for the evaluation of current vaccination and antibody-based therapeutic approaches towards SARS-CoV-2.",2020,2022,Ryerson University,219887,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C10672,173207,Rational design and standardization of serology diagnostics using immunoaffinity-targeted proteomics assays,"Current design of serology antibody tests is driven by convenience, speed of manufacturing, and affordability. Limitations of common serology tests include cross-reactivity and lack of standardization, which decrease diagnostic specificity and make such tests inappropriate to screen the general asymptomatic populations with low prevalence of COVID-19. Viral antigens used in the common tests assume detection of binding antibodies, but not necessarily neutralizing antibodies, further limiting the value of such tests. In our study, we will focus on rational design and standardization of serology diagnostics of SARS-CoV-2. We will utilize immunoassays and quantitative immunoaffinity-targeted proteomics assays to discover, verify and validate combinations of antigens and antibody isotypes which provide the highest diagnostic specificity and sensitivity. Unlike semi-quantitative serology immunoassays, our proteomic assays are quantitative, have no cross-reactivity, and provide ""gold standard"" solutions for inter-laboratory and international standardization of serology tests. Our study will facilitate improvements of diagnostic specificity of existing serology immunoassays, thus enabling population screening for the acquired immunity.",2020,2021,University of Alberta,164857.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C10673,173208,"Development of high throughput, inexpensive and scalable testing to detect SARS-CoV-2 antibodies using home blood collection kits and a fully automated ELISA antibody assay","Widely available testing is urgently required to diagnose past COVID-19 infections (detection of SARS-CoV-2 antibodies in serum) and to determine if immunity to COVID-19 is durable. We propose to develop and validate a ""home"" blood collection kit to be used with a high throughput antibody testing platform to provide a high throughput (10,000 tests/day in one centre), inexpensive (<$15/test), accurate and easy to use assay for SARS-CoV-2 antibody detection. An initial pilot study on 100 volunteers will identify ""home"" blood collection kits that are easy to use for the patients, maintain the accuracy of the antibody testing platform and provide the optimum performance by the laboratory. We will select one ""home"" blood collection kit to use on a larger group of 1500 hospital workers to scale up the testing and identify any issues with the blood collection or testing. The goal is to develop an inexpensive and easy to use antibody test which could be rapidly scaled up to be available to very large populations of Canadians. In addition, the volunteers will have repeat blood antibody testing 3 and 6 months following the initial testing. This will provide information on the prevalence of past COVID-19 infections, the incidence of new COVID-19 infections and if immunity indicated by SARS-CoV-2 neutralizing antibodies is present and durable.",2020,2021,Sinai Health System,370998.23,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C10674,173209,"The impact of COVID-19 on the health of physicians, nurses and other healthcare workers: an interprovincial cohort study","Healthcare workers are in the front line of infection from the COVID-19 virus and are working under very demanding conditions. Many may be asked to take on exceptionally long or difficult shifts, or to work in unfamiliar roles. All will be concerned about infecting their families, colleagues or patients and fear that they may not be able to provide adequate support for their patients or provide optimal interventions. The study proposed is recruiting doctors, nurses,health care aides and personal support workers and will follow them up to 12 months from the start of the epidemic in early March 2020, The specific aim of the first part of the study is to identify work factors associated with infection, as reflected in a positive blood test for antibodies to the virus. Rapid reporting of these findings may help prevent further infections going forward. In the second part of the study we are looking to attribute new cases of COVID-19 in health care workers to specific lapses in control measures (such as inadequate personal protection or failure to screen an infected patient). It will also document whether new cases, defined by antibodies, are fewer in the later phases of the epidemic, and if the associated exposure factors change over the year of the study. In addition, at each contact we will assess the mental health of the health care workers and the type of demands associated with higher rates of anxiety or depression. At the final contact, in March-April 2021 we will assess whether there is persistent mental-ill health associated with working through the epidemic, both in those who became infected and those who did not, but who worked with this threat always present.",2020,2021,University of Alberta,782847.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts,2020 +C10675,173210,"Immunity Passports for COVID-19: Scientific, Ethical, Policy and Design Implications","Around the world countries have taken serious steps to slow the spread of coronavirus pandemic. Some countries are considered using ""immunity passports"" as restrictions begin to lift to show who is immune to the virus and can potentially safely leave social isolation. It could particularly be valuable for identifying potentially immune front-line workers to help reduce the spread of disease in these settings. While offering a potential partial solution to lockdowns the approach is frought with legal, ethical and scientific concerns. Furthermore, the Canadian landscape is unique and any solution that is considered will need to be tailored for our setting both from a legal/ethical/policy perspective as well as a technology perspective. We will evaluate the potential use of an immunity passport in Canada. To do this we will look at immunity passports already being used or contemplated in other countries and consider the public health, ethical and legal implications of an immunity pass in Canada. We will consider whether an immunity pass should be used in Canada and if so for whom. We will provide guidance on the design of a potential Canadian digital immunity pass. This project is an important step in carefully examining the issue of immunity passes in a multi-disciplinary and un-biased manner.",2020,2021,Bruyère Research Institute/Institut de recherche Bruyère,181196.37,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues related to Public Health Measures | Health leadership and governance,2020 +C10676,173211,The COVENANT Study: COVID-19 Cohort Study of People Experiencing Homelessness in Toronto,"People experiencing homelessness are at high risk of COVID-19, which can spread rapidly in homeless shelters. The COVENANT study will obtain in-depth information on COVID-19 infections among people experiencing homelessness in Toronto. The study will follow a group of individuals who are homeless to identify new cases of COVID-19 over the next 12 months, identify factors that increase the risk of COVID-19, and build a model that accurately predicts the number of COVID-19 cases expected in the homeless population. Information from this study will be immediately useful to help guide public health strategies and housing interventions to prevent and control COVID-19 among people experiencing homelessness.",2020,2021,Unity Health Toronto,1454798.97,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics,2020 +C10677,173212,Are healthcare workers at higher risk of COVID-19 than other working adults? [Added supplement: COVID-19 Variant Network],"To date, there have been 69,000 confirmed or probable cases of COVID-19 in Canada. Healthcare workers are assumed to be at increased risk of infectious diseases, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2)/CoVID-19 compared to other working adults due to exposure to infective patients. However, no epidemiologic study has examined this assumption. This study is designed to determine incidence of SARS-CoV-2 in HCWs and other, non-healthcare working adults in other frontline service occupations. We will enrol 1640 people working in acute care hospitals (healthcare workers) and 820 people working in non-healthcare jobs from across Canada, including Edmonton, Toronto, Hamilton, Sherbrooke, and Halifax and follow them over 12 months to compare the incidence of SARS-CoV-2 over the 12-month follow-up, risk factors for infection, and several other outcomes in each group. Not only will this allow us to compare and contrast differences in the rates of infection but also in exposures to infective people from all areas of our lives, protective measures taken to reduce infection, and how those measures may affect the risk of infection. We will collaborate with researchers in the US and Puerto Rico, who are collecting similar information on healthcare and non-healthcare workers to determine the similarities and differences between countries and across sites. The results will inform optimal strategies for protecting the workforce, their families, and their patients/patrons.",2020,2022,Sinai Health System,1340485,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics,2020 +C10678,173213,"TARGet Kids! COVID-19 Study of Children and Families: Safe Return to School, Work, and Play","Across Canada and around the world, governments have implemented policies to limit the spread of COVID-19 including physical isolation, school and childcare closures. Many governments are now reducing these measures and returning children and families back to school and work due to a number of economic, social, and political factors. The World Health Organization recommends that governments seeking to relax physical isolation measures do so through two complementary approaches: 1) breaking chains of transmission through testing, isolating, and treating and 2) monitoring disease circulation through surveillance and serological surveys. We propose to pivot Canada's largest ongoing children's study, TARGet Kids, to provide high-quality, real-time data to monitor, quantify and characterize COVID-19 infection among children and parents. We aim to measure the incidence of new infections as well as previous COVID-19 exposure so that we can understand how COVID-19 is transmitted between children and their parents, risk factors for infection, disease severity, and health system use. We will also answer important questions about COVID-19 serological status of children and parents and the impact of physical isolation on child emotional and behavioral health as well as parent mental health and stress. We will provide evidence to support policy interventions to break underrecognized chains of transmission and reduce illness severity which will help policy makers guide children and their parents in safely returning to school, work and play. Key strengths of this proposal include a scientifically rigorous plan with a well-tested rapid implementation strategy that leverages Canada's largest children's cohort study to provide real-time high-quality data on COVID-19 community transmission.",2020,2021,Unity Health Toronto,745741.89,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease pathogenesis | Approaches to public health interventions,2020 +C10679,"173214, 175541","The COVID-19 Pandemic Among Sexual and Gender Marginalized Populations in Canada: Physical Distancing Impacts, SARS-CoV-2 Seroprevalence, and Health and Wellness Needs [Added supplement: COVID-19 Variant Supplement]","Physical distancing may have especially negative effects on marginalized communities such as lesbian, gay, bisexual, trans, queer, Two-Spirit, and other sexual and gender marginalized people (LGBTQ2+). LGBTQ2+ people are more networked socially and sexually compared with other groups. LGBTQ2+ also experience other health inequities such as cardiovascular disease, poorer mental health, and more substance use that may result in greater COVID-19 impacts. This study will determine how COVID-19 impacts LGBTQ2+ people across Canada. We will conduct an online survey of LGBTQ2+ people. Our findings will inform future public health action for LGBTQ2+ people to avoid unintended consequences such as intimate partner and family/domestic violence, anxiety, and depression. Participants will also be mailed a kit to collect a few blood drops to test for COVID-19. This approach may be an important tool for future COVID-19 testing, especially among rural, remote, and Indigenous communities.",2020,2022,University of Victoria,545579.63,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C10680,174027,Presence of Family,"The COVID-19 pandemic has impacted long term care (LTC) facilities across Canada. While restrictive visitation measures were important to limit the spread of the virus, the resulting prolonged separation from family members, had a tremendous impact on the well-being and quality of life of residents. This proposal is to support the implementation and sustainability of public health directives to increase the presence of family (including friends) in LTC facilities through 'support visitations' during COVID-19. This work aligns with CFHI's attention to practices that enhance the presence of family in LTC and the growing body of research that confirms family play a critical role in LTC. Family often assist with feeding, grooming and mobility and the absence of this partner in care during the pandemic resulted in hardship for residents, families and staff. As public health restrictions fluctuate in response to the second wave of the pandemic, it is therefore important to understand the implementation process for support visitations, what factors will support sustainability as the pandemic unfolds, and what the outcomes are of support visitations on residents, family and staff. Our aims are: 1.To explore and identify the contextual attributes of settings where support visitations have been adopted to articulate successful implementation processes. 2.To understand facilitators that support the implementation of support visitations as COVID-19 remains present in LTC and broader community settings. 3.To understand how family has been engaged/represented in the implementation process. 4.To assess the outcomes and impacts of support visitations on residents, family and staff. 5.To obtain insights into implementation and sustainability factors from other jurisdictions adopting similar support visitations practice.",2020,2021,Mount Saint Vincent University,112188.03,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C10681,174028,Presence of Family: (re)Integrating Family Caregivers,"The ""Presence of Family: (Re)Integrating Essential Care Partners in Ontario's LTC Homes"" project will help to develop and disseminate a promising practice intervention concerning the presence of family members in LTC. Our work will help essential care partners, who are chosen by the resident and who provide them with vital physical/psycho-social care, to have safe access to the LTC home. Drawing on existing approaches and tools supported by The Change Foundation, Ontario Caregiver Organization (OCO), Ontario Centres for Learning, Research and Innovation in Long-Term Care (CLRI), and the Canadian Foundation for Healthcare Improvement, the 3 homes we are working with have initiated a Designated Care Partner (DCP) program that combines training with a commitment to follow safety protocols and use ID badges, and facilitates greater access for essential care partners to the home. We will use developmental evaluation and a rapid scoping review to support the homes as they implement the intervention. To assist with spreading the learning from this work, we are convening an Advisory Board (AB) that includes members from participating LTC homes, family members, the Ontario Centres for Learning, Research and Innovation in Long-Term Care, Ontario Caregiver Organization, Family Councils Ontario, Ontario Association of Residents' Councils, Ontario Health-HQO, AdvantAge Ontario, Hotel-Dieu Grace Healthcare, and Bruyere Continuing Care.",2020,2021,Bruyère Research Institute/Institut de recherche Bruyère,112197.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C10682,174029,Dementia Isolation Toolkit,"The Dementia Isolation Toolkit (DIT) was designed and developed with LTCH stakeholders to address two primary aims: 1) To support the compassionate, safe and effective isolation and quarantine of residents of LTC during the COVID-19 pandemic, and 2) To support the moral resilience of LTC staff. In this project, we will evaluate the effectiveness of the DIT implementation program (DITi) and measure the impact of the DIT and its implementation on achieving effective, safe, and compassionate isolation, and reducing the moral distress of LTCH staff. We will explore the impact of the DIT and DITi on other relevant outcomes arising out of a developmental evaluation and the Common Measurement Framework. The impact of this project will include the development of evidence-informed implementation approaches and materials to facilitate the spread and sustainability of promising practices in person-centered isolation care and in supporting the moral resilience of staff, across the Canadian LTCH sector.",2020,2021,University Health Network,111819.27,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts,2020 +C10683,174030,Nutrition as Medication: from research to implementation,"Google translate: Malnutrition and weight loss are rampant in long-term care facilities (LTCFs). Yet their consequences are serious, including an increased risk of mortality and morbidity such as pressure ulcers and respiratory infections. This reality was exacerbated during the pandemic. LTC workers report that those with COVID-19 have seen their nutritional status deteriorate rapidly. At the same time, the unaffected residents also exhibited significant and undesirable weight loss. Interventions to prevent weight loss should aim to increase energy and protein intake. The use of oral nutritional supplements is a popular way to achieve this goal. However, the actual consumption of these products is rather low. Since 2017, an intervention nicknamed NAM for ""Nutrition as Medication"" has been developed and tested in ESLD by our team. This procedure suggests prescribing small doses of an oral nutritional supplement (30 or 60 ml) which are administered as a medication. The effectiveness of NAM has been studied. Preliminary results show a high administration rate (93-95%), a significant improvement in nutritional status and a decrease in pressure ulcers among residents. As a follow-up to these results, a guide was drawn up describing the NAM intervention, the principles that frame it, and the strategy suggested for a successful establishment in a LTCF. The NAM intervention appears to be a promising practice that could limit or even prevent the deterioration of the nutritional status of residents, whether or not they have COVID-19. However, the studies were carried out before the onset of the pandemic and the implementation guide therefore does not take this context into account. Thus, in order to better equip LTCs during the new wave of COVID-19, our team proposes the dissemination and scaling of the NAM intervention in LTCFs. Specifically, we propose to: 1) support the implementation of NAM within two Montreal LTCFs; 2) assess the implementation of NAM in terms of prescription and administration of treatment; 3) identify the facilitating and constraining factors for the implementation of the NAM; 4) identify the effects of NAM as perceived by workers and relatives / residents; and 5) revise the NAM implementation material.]",2020,2021,CIUSSS du Centre-Sud de l'Ile de Montréal,112198.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C10684,"174031, 174034",Preserving the links of LTC residents with cognitive disorders with their loved ones in the context of a pandemic: evaluation of the implementation and effects of virtual and in-person interventions,"Google translate: In Quebec, nearly 70% of deaths linked to COVID-19 are people living in long-term care facilities (LTCF). The restrictions imposed to reduce the transmission of the virus have deleterious effects on the elderly and consequences on family caregivers. In order to mitigate the negative effects, different strategies are used to maintain contact with relatives and thus promote protective actions for the mental and physical state of the elderly. However, the evaluation of the implementation and effects of innovative interventions in the context of a pandemic in elderly people with cognitive impairment have not been studied to date in Canada. In collaboration with 5 partner LTCFs, the goal of the project is to assess the implementation process, the viability and the acceptability of interventions aimed at favoring the presence of relatives (in person or virtually), as well as the effects on families. residents, their relatives and related costs. An evaluative research quote is preferred. A multiple case study will be used to describe the reality of the settings and the target actors, grasp the complex relationships between the different factors, document the degree and the variability of the implantation in the different settings and their results. Residents with cognitive disorders, their family caregiver and members of the care team will be recruited from each setting. Interventions to preserve contacts with loved ones and supported by the living environment can reduce the repercussions of isolation and have a considerable impact on anxiety, cognitive and behavioral symptoms and quality of life. By giving a voice to seniors, relatives and caregivers, documentation of acceptability will add evidence that tailored, humane interventions are viable and relevant in LTCFs.]",2020,2021,Université Laval,261762.6,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10685,174032,Strengthening Pandemic Preparedness in Long-Term Care,"Our Implementation Science Team is partnering with six long-term care and retirement home units in Saskatchewan, Ontario, and New Brunswick to support the reintegration of family caregivers. Furthermore, our team is also supporting the reintegration of other informal caregivers who play an important social role for residents who have no or less involved family caregivers. Using a pragmatic cluster randomized controlled trial, we will compare outcomes from three of the units that will focus on the reintegration of family caregivers alone and outcomes from the remaining three units that will focus on the reintegration of both family and other informal caregivers. Components of the intervention will include the identification of caregivers and a point of contact for caregivers, development of a consistent screening process and safety protocols for caregivers, establishment of a rapid appeals process, pre-entry preparation of caregivers through supportive education, and staff education to understand the essential roles of caregivers. Resident, caregiver, and staff outcomes related to loneliness, social support, resilience, and burnout will be measured before, during, and after the implementation of the interventions.",2020,2021,University of Regina,112029.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR) | Saskatchewan Health Research Foundation,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C10686,"174033, 175556",Supporting mental health and preventing moral injury among long term care+ workers: A mixed methods tool kit development and implementation study [Added supplement: COVID-19 Variant Supplement],"Long term care+ (LTC+) is at the center of tragic outcomes of COVID-19 and LTC+ workers are facing pronounced risk for occupational stress related injuries including moral injury. Moral injury results from guilt and/or shame that accompanies knowing what is needed yet being unable to do what is needed owing to constraints outside one's control (Dean, 2020). For LTC+ workers, moral injury may occur from experiences such as guilt over being required to ""police"" end of life visits where family members are only permitted to touch dying loved ones through gloved hands. Moral injury is being newly and necessarily applied to understand occupational stress of health care workers during COVID-19 because compared to individually focused concepts such as burnout, moral injury locates the source of problems in the structures and processes in which individuals are immersed. Our research question is: how do we support mental health and help prevent moral injury among LTC+ workers? Our objectives are to: 1-gather stakeholder evidence about worker mental health needs and moral injury risks; 2-collect stakeholder assessments of a selection of mental health support/moral injury prevention tools; 3-create and disseminate a mental health support/moral injury prevention toolkit tailored to LTC+ workers in pandemic conditions; and 4-develop theory and evidence-based implementation strategies for scaling and spreading our toolkit.",2020,2022,University of Calgary,151591.54,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C10687,174034,Préserver le lien des résidents en ESLD atteints de troubles cognitifs avec leurs proches en contexte de pandémie : évaluation de la mise en œuvre et des effets d'interventions virtuelles et en personnes,"Google translate: In Quebec, nearly 70% of deaths linked to COVID-19 are people living in long-term care facilities (LTCF). The restrictions imposed to reduce the transmission of the virus have deleterious effects on the elderly and consequences on family caregivers. In order to mitigate the negative effects, different strategies are used to maintain contact with relatives and thus promote protective actions for the mental and physical state of the elderly. However, the evaluation of the implementation and effects of innovative interventions in the context of a pandemic in elderly people with cognitive impairment have not been studied to date in Canada. In collaboration with 5 partner LTCFs, the goal of the project is to assess the implementation process, the viability and the acceptability of interventions aimed at favoring the presence of relatives (in person or virtually), as well as the effects on families. residents, their relatives and related costs. An evaluative research quote is preferred. A multiple case study will be used to describe the reality of the settings and the target actors, grasp the complex relationships between the different factors, document the degree and the variability of the implantation in the different settings and their results. Residents with cognitive disorders, their family caregiver and members of the care team will be recruited from each setting. Interventions to preserve contacts with loved ones and supported by the living environment can reduce the repercussions of isolation and have a considerable impact on anxiety, cognitive and behavioral symptoms and quality of life. By giving a voice to seniors, relatives and caregivers, documentation of acceptability will add evidence that tailored, humane interventions are viable and relevant in LTCFs.]",2020,2021,Université Laval,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2020 +C10688,174082,Implementing & Scaling Up the LTC Palliative Toolkit During COVID,"The impact of the COVID-19 pandemic on the Canadian long-term care (LTC) sector has been a national tragedy. Similar to many other countries, Canada has observed an unprecedented and exponential increase in the number of deaths in LTC due to the COVID-19 pandemic. Prior to COVID-19, our Strengthening a Palliative Approach in LTC (SPA-LTC) work highlighted how residents and families were faced with making critical and emotional end-of-life decisions without any preparatory discussions, resulting in stress and conflict. Most recently, the SPA-LTC team has developed a LTC palliative toolkit that can address the immediate LTC homes needs in response to COVID-19. The LTC toolkit includes tools and practices that support the following: 1. Engagement of residents and families across disease trajectories, including virtual informational resources and instructional videos 2. Workforce capacity development through (a) online staff education modules about implementing a palliative approach, and (b) supports to reduce stress and improve psychological health during COVID-19 and beyond 3. Development of organizational structures and processes embedded in the LTC home to promote a palliative approach to care The research questions/objectives of our CFHI funded study are to: A. conduct a scale-up assessment of the new LTC palliative toolkit in three provinces (ON, SK, NB) B. identify ways to adapt the LTC palliative toolkit for diverse regions and contexts C. document lessons learned from implementation in diverse settings D. evaluate the implementation and effectiveness of the toolkit in participating LTC homes during COVID-19",2020,2021,McMaster University,112198.5,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR) | NBHRF,Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Indirect health impacts | Health workforce | Institutional level capacity strengthening,2020 +C10689,174083,Implementation of Pathway for Goals of Care and End of Life Management in L,"There is a dire need to improve palliative care for frail older adults in long-term care (LTC) across Canada, since almost 40% of Canadians die in LTC. Palliative care, (i.e., supportive care for LTC residents during the final months or years of life), can relieve pain & other distressing symptoms & maintain quality of life. The COVID pandemic has drawn attention to the many barriers to providing palliative care to frail residents of LTC, including unpredictable dying trajectories associated with frailty, barriers to discussing end-of-life within Canadian culture, & limited palliative care knowledge & skills among LTC staff, combined with excessive workloads. Frailty is under-diagnosed in LTC & is often unpredictable in its presentation & progression. However, it is a life-limiting condition associated with increased comorbidity, high levels of physical, emotional & social disability, & an unpredictable illness trajectory. Recent research by our team (unpublished) identified the steps needed to effectively provide palliative care in LTC: i) restructure the physical setting, ii) provide education/skills training, iii) deliver care integration, iv) engage families & v) broaden the meaning of frailty. The COVID pandemic has highlighted the urgent need to improve palliative care that is specific to LTC residents with frailty, yet effective & practical care strategies for this complex care setting must be developed. We propose developing a clinical pathway that focuses on frailty & early palliative care for LTC residents, leading to improved care planning & outcomes. Our overarching goal is to develop an evidence-based care pathway for early recognition of frailty & initiation of early palliative care for LTC residents, appropriate to degree of frailty. An integrated knowledge translation approach & the Knowledge to Action (KTA) cycle will be used to achieve the following three research objectives: • Develop an evidence-informed care pathway focused on diagnosing & managing frailty, which includes incorporating early palliative care in LTC (KTA: Knowledge Creation); • Understand barriers & facilitators to this care pathway in LTC. (KTA: Assessing Barriers); • Develop & pilot an implementation strategy for the pathway. (KTA: Select & Tailor Implementation Interventions).",2020,2021,University of Calgary,110610.5,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2020 +C10690,174084,"Making ""nonessential"" family/volunteer caregiving essential in LTC","The no visitor policies put in place because of Covid-19 have resulted in substantial negative outcomes for residents, families, caregivers, volunteers, and health care professionals. This project will provide rigorous data to address the following implementation questions: (1) can new procedures to distinguish between family/volunteers/caregivers who are essential partners in care and those who are not be implemented successfully and sustained over time; (2) if family/volunteers/caregivers are not permitted in the home, can alternate initiatives for ensuring virtual contact be successfully implemented and what impact do those have on family, resident and health care professional outcomes. To answer these questions, the research team, in close collaboration with the knowledge users, will (1) gain an understanding of the safety, efficacy, effectiveness, and ethics of the current response to COVID-19 that pertains to family/volunteer/caregiver presence in the long-term care setting; (2) increase the evidence about the impact of reduced levels of family/volunteer/caregiver presence as a result of COVID-19 on the emotional and psychosocial well-being of residents, caregivers, and health care professionals, (3) engage stakeholders in generating solutions and recommendations to revisit policies on family/volunteer/caregiver presence to improve the current situation and improve the preparedness for future pandemics and outbreaks, and (4) evaluate the implementation, adoption, effectiveness and sustainability of interventions and policies regarding family/volunteer/caregiver presence; and identify and address barriers and facilitators to the uptake of interventions and policy changes across settings.",2020,2021,University of Ottawa/Université d'Ottawa,99899.89,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Research to inform ethical issues in Clinical and Health System Decision-Making | Indirect health impacts | Policy research and interventions,2020 +C10691,174085,Finding a Better Balance: Implementing Family Presence in Ontario LTC Homes,"Long-term care (LTC) homes have experienced the worst of the coronavirus disease 2019 (COVID-19) pandemic in Canada, with residents of these homes accounting for nearly 80% of all Canadian COVID-19 deaths. Between March and April of 2020 when outbreaks and deaths intensified in Canadian LTC homes, provinces across the country implemented strict blanket ""no visitor"" policies as part of their LTC infection prevention and control (IPAC) strategies. In response, members of our implementation science team (IST) published National Institute on Ageing (NIA) guidance in July 2020 on the reopening of Canadian LTC homes to family caregivers and visitors during the COVID-19 pandemic. This guidance was widely disseminated, and led to several provinces updating their visitor policies. Reports from residents and family caregivers collated by our team suggest an inconsistent and incomplete implementation of this updated family presence policy. Our multiphase project will accomplish the following objectives: 1) Update provincial data collection tools to capture metrics on caregiver and visitor access to LTC homes and LTC resident absences and their relation to relationship with COVID-19 outbreaks in LTC homes; 2) Conduct an analysis of provincial quantitative data on caregiver and visitor access and qualitative LTC home data on the barriers and facilitators to implementing family presence; and 3) Execute and study an implementation strategy at our partner LTC homes, and create a learning collaborative on the implementation of family presence in LTC homes across the province.",2020,2021,Ryerson University,112200,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +C10692,174086,Guidelines to Support Nursing Home Staff,"There is an urgency to respond to the ongoing challenges facing the long-term care home (LTCH) sector which have been uncovered by the COVID 19 pandemic. To address these challenges and contribute to mitigating the effects of any future outbreaks, members of our team along with their international colleagues have developed recommendations to support staff during COVID 19 (i.e., provide clear direction and guidance, keep staff healthy, promote effective human resource policies, implement new clinical practices) and improve infection control practices in nursing homes (McGilton et al., 2020, JAMDA). Preliminary findings from our ongoing work with Nurse Practitioners (NPs) have provided convincing evidence that NPs are well positioned to disseminate and implement these recommendations in LTCHs. This implementation study will determine the steps and resources that are necessary to adapt the guidelines to the context of and to effectively implement them in 2 LTCHs. The focus of the grant is to: 1) Adapt the recommendations to the context of the 2 LTCHs (Phase 1); and 2) Pilot test and evaluate the adaptation of the recommendations by focusing on feasibility, fidelity, cost and sustainability of implementing them per each LTCH context (Phase 2). The LTCHs in Ontario were selected as they have affiliated NPs and they expressed readiness to adopt the recommendations and to commit NP time and resources. We will combine the Consolidated Framework for Implementation Research (CFIR) for modifying and adapting the recommendations to LTCH settings; and the principles from Community-Based Participatory Research (CBPR) to guide our implementation approach. We anticipate that the uptake of the guidelines will have a significant impact on the staff job satisfaction in LTCH and retention rates, and will reduce mortality and admission rates to hospitals. We also believe that continued improvement of the guidelines and its eventual spread and scale up will make a profound contribution to ensuring residents in LTCHs receive the best care possible.",2020,2021,Toronto Rehabilitation Institute,105655,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,CABHI | Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control | Health Systems Research,Restriction measures to prevent secondary transmission in communities | Health workforce,2020 +C10693,174105,COVID-19 Evidence Network to support Decision-making (COVID-END),"The science about how to prevent and manage COVID-19 and its spill-over effects on society is changing rapidly. Summaries of the best available science (which we call evidence syntheses) are the best place to turn when making decisions about public-health measures (e.g., wearing masks), clinical management (e.g., prescribing drugs), health-system arrangements (e.g., making the most of virtual doctor visits), and economic and social responses (e.g., adjusting schools and workplaces). COVID-END will bring together: 1) 25+ Canadian evidence-synthesis teams; 2) leaders of key Canadian initiatives that support the use of science by citizens, service providers and policymakers; 3) diverse citizen partners from across Canada; 4) Canadian professional bodies; and 5) policymakers and leaders from Canadian governments and health authorities. COVID-END will: 1)prepare and update evidence syntheses at the request of Canadian decision-makers in timelines ranging from 4 hours to 10 days; 2)maintain an inventory of the best evidence syntheses for COVID-19 decisions to ensure that Canadian decision-makers have available at all times the most updated summarized science; 3)work with Canadian decision-makers to ensure that their most urgent questions are prioritized and responded to by the most appropriate team in a timely way and that these decision-makers have the capacity to find and use the available science in their decision-making; 4)keep alert to emerging issues where evidence syntheses may be needed in the future; and 5)work with Canadian and global partners to reduce duplication and enhance coordination in the evidence response to COVID-19. COVID-END will undertake (or co-create) its work in close partnership with citizens and with the decision-makers who pose questions and whose existing processes we need to intersect with. COVID-END will disseminate and support the use of its work both directly and through many existing initiatives.",2020,2020,McMaster University,770000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C10694,174125,Canadian Longitudinal Study on Aging (CLSA): Building COVID-19 Platform for Research in Canada,,2020,2020,McMaster University,923989.99,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,,,2020 +C10695,174189,The Canadian Network of COVID-19 Clinical Trials Networks,"Nearly 350,000 Canadians have been diagnosed with COVID-19 infection. In Canada, the elderly have been particular vulnerable, with long-term care homes experiencing the greatest burdens of illness and mortality. Civil society and our usual social fabric have been torn, due to illness, loss, school and work interruptions and social distancing. No Canadian sector has been untouched. There is an ongoing risk of acute health care systems being overwhelmed, including the care for our sickest Canadians. To meet the challenge of knowing how to best prevent, diagnose and treat COVID-19, we need coordinated and supported national research, that is responsive to the needs of citizens, patients, families and health systems, and benefits from the expertise of clinicians, researchers, industry, our public health, clinical and biomedical research infrastructure. Bringing the best prevention, diagnostic tests and treatments to Canadians as quickly as possible demands that we work together as Canadians, and with partners around the world. The Canadian Network of COVID-19 Clinical Trials Networks is a diverse, inclusive partnership that will bring resources to partners to get the most from our research response. We will engage citizens and patients, help set dynamic research priorities involving the public and private sectors, facilitate collaboration and resource sharing, harmonize clincial trial procedures, make the research regulatory steps easier, connect data from many clinical trials, mobilize the knowledge we gain to prevent infection, treat patients, help them recover, and end this pandemic. This Network will not only help to get the most from the Canadian COVID-19 research response, but will build research capacity and better prepare us for the future.",2020,2020,Sunnybrook Research Institute,4620000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Research on Capacity Strengthening,Cross-cutting,2020 +C10696,174742,MedSafer- Optimizing Prescribing for Pandemic Preparedness,"Residents of Long-Term Care (LTC) are generally older than their community-dwelling counterparts, have multiple medical comorbidities, complex care needs, and often take multiple medications (on average 10 or more daily). It is clear from the first wave of the pandemic that this vulnerable population is at highest risk of severe complications from COVID-19, including death. A multi-pronged approach including comprehensive medication management is urgently needed to optimize care for people living in LTC during the pandemic and beyond. MedSafer is a Canadian-made electronic decision support tool for medication management. It is a software that cross-references a patient's medical conditions with their medications and provides a personalized report directed towards the prescriber, with a roadmap for optimizing a person's medication list. MedSafer interfaces with electronic medical records (EMRs) to make use of existing electronic healthcare data to provide individualized medication management reports directly within the EMR. There is sufficient evidence from research into medication management to justify action in typical settings, but it is unknown whether this is the case during a pandemic. This is what we aim to study. Within the context of a pandemic, medication management with MedSafer may help residents and LTC staff by 1) minimizing pill burden; 2) reducing unnecessary clinical encounters; 3) decreasing adverse drug events (ADEs); and 4) preventing ADE-associated requirements for escalation of care, such as hospital transfers. This will be a mixed-methods hybrid type 3 controlled before and after implementation study taking place over 12 months that will examine both the process and the outcomes of providing integrated MedSafer reports in the PointClickCare EMR to augment usual quarterly medication reviews. Some of the research questions we seek to answer are the following: 1. Is medication management supported by the electronic decision support tool MedSafer FEASIBLE during a pandemic? 2. What is the ACCEPTABILITY of the intervention to LTC home staff? 3. Does MedSafer augment the role of pharmacists who cannot visit the home during the outbreak (EFFECTIVENESS measured by a decrease in potentially inappropriate medications and ADEs)?",2020,2021,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,98399.4,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C10697,174743,Enhancing the Lives of Older Canadians in Long Term Care in Newfoundland,"This Newfoundland-based Implementation Science Team project will address specific practices described in the document ""Reimagining care for older adults: ix promising practices and policy options for LTCs and PCHs"" (CFHI); based on desire of LTC decision makers we are focusing on #6 - presence of family- The research will focus on LTC residents and family-centred care intervention for the LTCs. This intervention includes: 1. Virtual solutions such as e-visit by providing i-pad to facilities for day to day visit with their family and electronic messaging between LTC staff and the family to inform them about the resident health conditions; 2. Visitation policy (screening the family for COVID 19 according to the Eastern Health guidelines and maximum 2 visits per day per person; 3. Virtual mental health support for residents and family. 4. Residents care plan for COVID and non-COVID including virtual care, person-centred integrated care plans for all residents, at least of individual with IPC training among the LTC leadership to assist the LTC in case of an outbreak.",2020,2021,Memorial University of Newfoundland,112200,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C10698,174744,COVID-19: Implementation of virtual P.I.E.C.E.S™ for resident care planning with family to build and sustain team collaboration and resilience for the workforce in LTC,"COVID-19 restrictions resulted in profound isolation for older adult residents in long term care (LTC) homes, which exacerbated their physical, social, and mental health care needs (Chu et al., 2020). Illness due to COVID, in combination with LTC workplace challenges, also led to losses of staff and greatly impacted the mental and physical health of the remaining workforce, compounding the detrimental effects on residents (Shechtera et al. 2020). The primary goal of the proposed research is to improve pandemic preparedness, provide a workforce strategy for integrated resident care and safely engage family in care partnerships, to avoid the recurrence of the detrimental effects of the first pandemic wave. A secondary goal is to provide evidence for practices and policy and build research capacity that can be implemented in LTC homes. Facing the likelihood of future COVID-19 outbreaks coinciding with flu season, LTC homes, residents, their families, and staff need a clear strategy in place to better manage resident care. A plan that involves family members, promotes communication, and supports the resilience of Registered Practical Nurses (RPNs), the largest front-line regulated workforce, and staff so they can practice safely and effectively during a pandemic. This project, situated in two partner LTC homes, will investigate a novel virtual intervention of P.I.E.C.E.S.™ (PIECES) for team-based planning of resident care.",2020,2021,Western University,112200,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health service delivery | Health workforce,2020 +C10699,174745,Harnessing a novel multi-institutional cross-sectoral partnership for providing enhanced COVID and non-COVID care in long term care homes,"In April 2020, responding to the first wave of the COVID-19 pandemic, we developed and rapidly implemented a multi-institutional model of collaborative virtual care providing rapid access to specialists and diagnostic services for long term care homes (LTCHs) in the Greater Toronto Area (GTA). Coincidentally, we called our program LTC+ (www.ltcplus.ca), and it has received attention from health system leaders and policy makers as well as the media.To avoid confusion, we refer to our program as GTA-LTC+. Initially GTA-LTC+ focused on preventing avoidable hospital transfers, reflecting the perceived priority at the time of ensuring acute care capacity during the pandemic's first wave. However, meeting care needs in the LTC setting has intrinsic value, offering person-centered care aligned with residents' goals of care. Minimizing avoidable exposures to acute care settings decreases risks of delirium, care discontinuity and functional decline. Even prior to COVID-19, the need already existed for more coordinated access to specialist care, ideally consolidated in a single partner hospital for any given LTCH and minimizing the frequency with which residents need to receive such care outside of their homes. We thus came to view GTA-LTC+ as a program which would improve care even without the problems posed by COVID-19, but with additional value in ensuring that residents can continue to receive high quality, specialized care during future outbreaks. GTA-LTC+ uses a hub and spoke design, where 6 hospital hubs provides rapid access to a suite of virtual and in-person clinical and diagnostic services to geographically-associated LTCHs in 2 of the 5 Ontario Health Regions (i.e., Toronto and Central). Implementation of the intervention was guided by the RE-AIM framework as we grew it from just 3 pilot sites to 52 LTCHs. As the health system braces for the pandemic's second wave, this intervention may represent a solution to improve both COVID-19 and non-COVID-19 care and minimize unnecessary acute care transfers. Yet, the overall impact of the intervention requires further evaluation before the model can be scaled, as does the value of specific enhancements to the intervention currently available at only some sites. We will use a mixed-methods study design to address the following objectives: 1. Evaluate the degree to which GTA-LTC+ provides adequate access to COVID-19 and non- COVID-19 care in LTCHs using reductions in acute care transfers as a marker for such access 2. Explore the impact of GTA-LTC+ on the care experience of residents, caregivers, staff and providers at the 6 LTCHs from the GTA-LTC+ cohort enrolled in the national LTC+ program 3. Identify factors influencing the adoption and maintenance of the intervention to inform ongoing program implementation and spread.",2020,2021,Women's College Hospital,112170.08,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2020 +C10700,174746,Design interventions to support IPAC in LTC,"Canada's Long-Term Care (LTC) sector has been disproportionately burdened by COVID-19, accounting for 85% of all COVID-19 deaths nationwide. LTC residents are particularly vulnerable given their advanced age, reduced immune system capacity and multiple underlying health conditions. But LTC staff have also faced an increased risk of infection due to frequent multi-site work coupled with personal protective equipment (PPE) shortages in work environments that may not support infection prevention and control (IPAC). As a result, LTC staff members represent over 10% of confirmed COVID-19 cases in Canada (as of May 25), with nine reported deaths. Given the frequent close contact between LTC staff and residents, preventing infection among staff has, and will continue to be, an important infection control strategy to reduce further morbidity and mortality among LTC residents and staff while ensuring quality and continuity of care. Existing IPAC protocols designed to help mitigate the risks of staff-to-staff transmission in shared settings are often based on acute care environments and may not 'fit' or support the unique characteristics of LTC, which include: a variety of shared working and respite spaces; spaces which are detailed to be home-like and may in turn be difficult to clean or disinfect; crowding in small staffing areas which weren't designed to support physical distancing; dynamic traffic in shared spaces; open shared spaces which may be difficult to monitor access or inadvertent contamination due to open access; and the organic flow of staff, allied health, contractors, residents, family and friends entering and leaving the home and moving throughout the home, to name just a few considerations. Since March 2020, IPAC protocols had to be rapidly developed, deployed and learned in LTC to respond to the pandemic. The critical nature of this fast-evolving situation, coupled with a lack of information on the impact of such protocols within the context of actual use patterns and behaviours in shared spaces, highlights the urgency of improving our understanding of factors that may influence transmission risks between LTC staff, and in turn the wellbeing of LTC residents, family members and friends. This knowledge is required to improve our ability to modify, renovate and design LTC and senior's homes to be more resilient in the face of infectious outbreaks while maintaining their friendly, residential, people-centred characteristics. Within this context, we want to support homes by studying: 1) How the design of shared staff spaces (or lack thereof) and staff use patterns may be undermining IPAC; 2) What rapid and low-cost design interventions may help reduce such risk factors?; 3) In what ways might our design interventions reduce these risk factors?; and 4) What is the cost and cost-effectiveness of the proposed interventions?",2020,2021,Carleton University,112200,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience",IPC in health care settings | Approaches to public health interventions,2020 +C10701,174747,RESPECT-LTC,"Palliative care is commonly misunderstood as only being relevant for people who are actively dying and in the final weeks or days of life. However, the relief of suffering through the provision of holistic and compassionate care is an essential component of care for all patients with a life-threatening illness. For care of residents with and without COVID-19, palliative care approaches are vital to quality care in LTC. However, the capacity of LTC homes to introduce and embed palliative care approaches can be hindered by poor communication about prognosis. Clinicians, even palliative care specialists, often have difficulty estimating survival beyond a few weeks. Unfortunately, many existing frailty and mortality indices present the outcome as a probability of death or a risk score on a mortality-based index, which are not easily actionable for either clinicians or patients and their families. In this project, we propose to rapidly implement and evaluate the Risk Evaluation for Support: Predictions for Elder-life in the Community Tool in LTC (RESPECT-LTC) to support their ongoing efforts to embed palliative approaches to care in their processes and culture. RESPECT-LTC is a mortality-risk communication tool that accurately predicts an older person's six-month mortality risk as well as life expectancy to inform clinicians' decisionmaking regarding the initiation of palliative and/or end-of-life care. RESPECT-LTC was co-designed with patients and caregivers. It informs care providers, residents and their families when the resident may be approaching the end of life by estimating their survival in days, weeks and months-a metric that has been shown to be patient-oriented and meaningful for care planning. In alignment with the goals of the LTC+ program, we will support LTC homes' implementation and evaluation of promising practices in palliative and end-of-life care based on prognoses generated from RESPECT-LTC. We will achieve this by: 1. Enhancing the assessment of, and clinical decision-making, regarding of palliative care needs using RESPECT-LTC, a validated evidence-based tool; 2. Assessing the acceptability of RESPECT-LTC by individuals spanning the decision-making and care hierarchy in LTC; 3. Supporting implementation science-informed skills training in end-of-life communication for clinicians practising in LTC; 4. Developing recommendations for care pathways in LTC residents based on prognostic information (i.e., mortality risk and life expectancy) generated from RESPECT-LTC; 5. Evaluating the effectiveness of RESPECT-LTC in supporting a palliative care approach and improved resident outcomes in LTC.",2020,2021,Bruyère Research Institute/Institut de recherche Bruyère,112200,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research","Communication | Indirect health impacts | Social impacts | Medicines, vaccines & other technologies",2020 +C10702,174749,Improving prescribing of medications at the end-of-life in long-term care homes through the COVID-19 pandemic,"This proposal involves 2 provinces (Ontario and Alberta) where knowledge users have identified a need to improve palliative care in long-term care (LTC) homes, and where investigators have ready access to data to conduct rapid implementation research. Both provinces have had 70%+ of COVID-19 deaths in LTC homes. We propose 3 main phases/objectives: 1. Data measurement to detect variations in end-of-life palliative medication prescribing (proxy to palliative care delivery) and evaluate changes post-intervention; 2. Mixed methods evaluation to deepen understanding of the barriers and facilitators of end-of-life prescribing in LTC; and 3. Intervention to support homes in both provinces, focusing on those most challenged to provide end-of-life care during COVID-19.",2020,2021,Bruyère Research Institute/Institut de recherche Bruyère,112189.53,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C10703,174804,A proposal to evaluate safer supply pilot programs in Canada,"Safer (or 'safe') supply is defined as a legal and regulated supply of drugs with mind/body altering properties that traditionally have been accessible only through the illicit drug market. Safer supply programs have been established in Canada primarily to reduce overdose caused by the unregulated (""street"") drug supply, which is saturated with high-potency opioids (e.g., fentanyl) and potentially toxic adulterants (e.g., etizolam). Beginning in 2019, Health Canada has been funding a growing number of safer supply pilot projects (SSPPs). SSPPs provide standard dose pharmaceutical-grade opioid formulations via dispensation to individuals. These programs appear beneficial but have yet to be subject to systematic evaluation. Understanding how they are organized, the makeup of their clients, and their impact on overdose and other drug-related outcomes is critical to developing an effective response to the opioid overdose epidemic. We propose an implementation science approach that will a) assess SSPP organizational structures, delivery models, and the contexts in which they are being implemented; b) identify the makeup of their clients and assess how SSPPs are impacting client health across distinct settings, and c) track how these programs evolve, particularly in light of the impact of disruptions from COVID-19.",2020,2024,Unity Health Toronto,933126.48,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C10704,174805,Investigating access to and outcomes from supervised drug consumption services in British Columbia before and during the COVID-19 pandemic,"Canada continues to face two public health epidemics. The opioid overdose crisis continues to account for considerable suffering and death. This is true of British Columbia where a public health emergency was declared in response to the overdose crisis, and where over 6000 people have died of overdose since 2016. More recently, COVID-19 emerged and is responsible for significant illness, hospitalizations, and deaths. Unfortunately, it has now become apparent that the emergence of COVID-19 has worsened the overdose epidemic, due to a range of factors, including restrictions imposed to reduce COVID-19 transmission (e.g., social distancing, isolation) and disruptions in access to overdose prevention programs. Supervised drug consumption services (SCS) are settings where people can consume drugs under the supervision of healthcare professionals who provide emergency response in the event of an overdose. Existing research suggests that SCS reduce the risk of overdose death, and to date, no one has ever died of an overdose in an SCS. While there is now growing concern that access to SCS has been compromised during the COVID-19 epidemic, little is known about how COVID-19 may be impacting access to and outcomes from SCS. To better understand these impacts and inform policy and practice specific to SCS, we propose to undertake research on SCS and COVID-19 in two settings in British Columbia (Vancouver and Surrey). We aim to use our existing research infrastructure to examine changes in SCS use over time (pre-post COVID-19), identify those who are and are not accessing SCS, and specific barriers to SCS access. We will also seek to determine how changes in SCS use during the COVID-19 era have affected key outcomes from SCS implementation, including changes in risk behaviours, addiction treatment use, and the use of public spaces for injecting. Lastly, we also use this project to generate quality data that can be used by others in in modelling and cost-effectiveness studies.",2020,2021,British Columbia Centre on Substance Use,194270.7,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Health Systems Research | Policies for public health, disease control & community resilience",Health service delivery | Community engagement,2021 +C10705,174806,A rapid assessment of the impact of the COVID-19 pandemic on supervised consumption services in Canada,"The COVID-19 pandemic and associated public health measures have increased overdose risk for people who use drugs. Since the start of the pandemic, provinces across Canada have reported record high overdose deaths, likely due to illegal drug market disruptions, physical distancing, and self-isolation measures. These measures may result in delayed intervention in the case of overdose, as more people may choose to consume their drugs alone. These increased overdose risks are occurring in the context of decreased access to health services like supervised consumption services (SCS), which have had to adapt to prevent risks of COVID-19 transmission amongst staff and participants. SCS are a core component of Canada's overdose response, and there are currently 38 federally-sanctioned SCS in Canada. SCS originally developed under a harm reduction approach to substance use and provide safe spaces where people consume drugs, are monitored for overdose, and receive access to health and social care. Ensuring access to SCS during the COVID-19 pandemic is thus important for addressing overdose risk, but we do not know the extent of service disruptions in Canada. Therefore, we aim to: (1) systematically describe SCS use patterns prior to, and after the onset of the COVID-19 pandemic; (2) compare impacts of COVID-19 on SCS across different service models and regions; (3) assess SCS staff perspectives on how the COVID-19 pandemic is shifting care for people who use drugs; and (4) outline staff-identified solutions for ensuring SCS access during the pandemic and other crises. Our findings and knowledge translation resources will directly support SCS in adapting to COVID-19, help ensure ongoing and equitable access to these services, and address the combined harms of overdose and COVID-19 for people who use drugs regionally and nationally.",2020,2021,University of Alberta,166734.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C10706,174807,Supervised Consumption and COVID-19 in ON: an Evaluation (SCCONE),"The opioid overdose crisis and the COVID-19 pandemic are 2 major public health problems in Canada. People who use drugs are at high risk for harms during the pandemic due to changes in the drug supply, uncertain economic instability, and increased isolation. Supervised injection services may help to address these risks. Currently, there are 19 supervised injection sites in Ontario. Fewer than 1 in 10 opioid-related overdose deaths in Ontario occurred in a region in which there was a supervised injection site. Our study will examine the best models for supervised injection sites, how these sites can be sustained over time, and how to address barriers to using sites for specific groups, including people who are racialized and Indigenous, women, and people who use stimulants. We will use a mathematical model to examine how to maximize flow through supervised injection sites. We will also address the public health effects of supervised injection sites during the COVID-19 pandemic and both the experienced and potential impact of scaling up or scaling down supervised injection services in Ontario. Our study will have direct relevance for public health and health policy and will help all stakeholders address which SCS models are the best, for which people, in which contexts, and at which times, including during the COVID-19 pandemic.",2020,2021,Unity Health Toronto,195000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Indigenous People | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C10707,174808,Evaluation of supervised consumption services in Montreal in the context of COVID-19,"Supervised consumption services (SCS) aim to reduce the harms of injection drug use by providing a controlled environment for people to inject drugs, with emergency response in the event of an overdose, sterile injection supplies, drug checking, counseling, referrals, and other supports. The ongoing COVID-19 pandemic has disrupted the operations of these vital services, and fatal overdoses have dramatically increased in Canada since the onset of the health crisis. This study will examine the impact of COVID-19 on supervised consumption services and their attendees. First, we will compare service usage before and during COVID-19 by looking at the number of visits to the services, the number of new attendees, the number of on-site overdoses, and the types of substances being consumed, among other factors. We will use this data to develop an idea of the different groups of people who use supervised consumption services, and to assess whether attendee groups have changed as a result of the pandemic. Building on these results, we will model the impact of service changes on future overdose rates in the population, and project the potential to avert these harms by improving retention and engagement with supervised consumption services in the future. This study will generate insights into the functioning of supervised consumption services during the COVID-19 pandemic. Our results will help develop a clearer picture of attendee profiles before and during the pandemic, supporting supervised consumption services in targeting underrepresented groups. These findings will support recommendations for supervised consumption service operations and policies in the context of health crises, with the ultimate aim of reducing overdose rates both within and beyond supervised consumption sites. Guidelines and best practices developed in response to the pandemic will also serve to prepare knowledge users for future public health emergencies.",2020,2021,Centre hospitalier de l'Université de Montréal,194922,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research","Social impacts | Medicines, vaccines & other technologies",2021 +C10708,174865,"Optimization of the resilience to COVID-19 of long-term care institutions serving linguistic-cultural minorities in Manitoba, New Brunswick and Quebec: evaluation and co-construction of innovative approaches to optimize the social participation of families and caregivers in the challenges of potential outbreaks","Google translate: In Canada, 81% of deaths from the first wave of COVID-19 occurred in long-term care facilities (LTCF). In addition to this heavy toll, there is the threat of a second wave, which has already started in several jurisdictions. Public health measures that reduce contact with professionals, families and caregivers, lock up LTCFs. This particular context, which includes the restriction of visits, deepens the isolation and loneliness of the elderly (PA), particularly in a minority context. These collateral effects that make the IPs more vulnerable, not anticipated in the response, are today strongly experienced by the LTCFs. This unique and alarming situation forces LTCFs to develop promising practices for the present and future outbreaks and ensure the maintenance of social capital between IPs and their families and caregivers, as well as with staff, to break the isolation. and loneliness. In Quebec, a third of COVID-19 infections concern health care personnel. LTCFs, the ideal setting for seasonal outbreaks (eg influenza), already operate with insufficient staff, exhausted and fearful of infection. The vast majority of LTCs do not integrate digital technologies optimally to support staff. No one was prepared for the challenge of COVID-19, but the innovations implemented so far indicate islands of success, winning practices that our project will capitalize on, by focusing on linguistic-cultural minorities (English-speaking ESLDs). of Quebec and francophones of Manitoba and New Brunswick). Indeed, few initiatives concerning COVID-19 are reported with these populations and the situation could be more difficult among IPs in the context of linguisticocultural minority who usually encounter challenges in accessing the health system. Given the very limited number of LTCFs dedicated to these minority populations in the provinces, families and relatives are often geographically far away, or even in other provinces of the country, digital solutions appear particularly relevant. Of the six strategic options, the project revolves around the presence of families (# 6), as key partners in caring for and breaking loneliness. Subsidiarily, it involves the components 2) prevention and 3) effective. The goal of the project is to identify and implement best practices and promising policies and create a community of practice to alleviate the isolation and loneliness of IPs in per and post COVID-19 to ensure safe and quality care in LTCFs.]",2020,2021,Université de Saint Boniface,112088.55,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research","Social impacts | Medicines, vaccines & other technologies",2020 +C10709,174882,"All-cause and cause-specific acute morbidity attributable to Covid-19 epidemic, severe Covid-19 symptoms, and adverse birth outcomes in Canada.","Since the first recognition of a novel coronavirus SARS-CoV-2 in December 2019, the virus has infected over 36 million people globally and caused over one million deaths by October 2020. The true number of infected people is largely unknown, however, due to inconsistent testing and reporting of positive cases. The global pandemic has overwhelmed health care systems and public health measures were introduced to contain the spread of the virus. This study will address important questions about the health impacts of the Covid-19 pandemic on Canadian population. While we do know the exact number of Covid-19 positive individuals in Canada, we can examine increases in hospitalizations for all severe diseases and their complications. Current data show that older people are most severely impacted by the epidemic, however, it is not known whether males or females are affected in different ways, or whether emergency visits for other conditions, for example mental health problems, have increased during the pandemic. We will examine also past medical history among patients with Covid-19 disease as a potentially important predictor of disease severity. Finally, childbearing women may be vulnerable to SARS-CoV-2. While the current literature provides inconsistent results with this respect, more information is needed to describe the risk factors and pregnancy outcomes in Canadian women. We will use national data collected by the Canadian Institute for Health Information (CIHI). CIHI has assigned a new diagnostic code for Covid-19 disease and maximized its efforts to obtain information on all hospitalized cases. In summary, our results will help to identify vulnerable subgroups of population that are highly affected by the direct and indirect effects of the pandemic. We will also clarify the role of prior medical history on the prediction of severe Covid-19 symptoms, and provide insights into the effects of Covid-19 on Canadian pregnant women and their offspring.",2020,2022,University of British Columbia,132957,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Pregnant women | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Post acute and long term health consequences | Indirect health impacts,2021 +C10710,174883,The unintended consequences of implementing stay-at-home policies during the COVID-19 pandemic: Violence outcomes in children and youth in Canada,"Although stay-at-home measures during pandemics are implemented to protect the population, a serious consequence of quarantine has been heightened risk of child maltreatment, such as physical abuse, sexual abuse, emotional abuse, neglect, and exposure to family violence. During the height of the pandemic, public health leaders and governments required Canadians to stay at home and to maintain social distancing if, and when, they were out. These policies, and the response to them, undoubtedly saved lives. We are unsure however, of how certain COVID-19 policies may have affected other health outcomes. A recent Children First Canada report called ""Raising Canada 2020"" reported that children and youth, as well as those less fortunate, may have suffered more than others as the result of COVID-19 policies. This report also states that preventable injury is the number one threat to children and youth in Canada, and called violence against children the ""hidden crisis"" of the pandemic. In the early days of the pandemic, Kids Help Phone calls in Vancouver increased drastically, as did as the number of reported domestic incidents, sexual assaults, and a rise in reported gun violence in Toronto. Despite this, we do not have data on the number of children and youth affected by violence during the COVID-19 restrictions. Our research project will use several sources of data to better understand how many children and youth suffered a violence-related injury during the pandemic. We will use data to report on the type of injuries that occurred and how, so that this information can inform us of what to do to prevent this from happening in the future.",2020,2023,B.C. Children's Hospital,211522.5,Other,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C10711,174884,Covid-19 and infodemic: information practices of groups vulnerable to COVID-19 in Quebec in the context of a pandemic.,"Google translate: The historic measures put in place to protect the population from COVID-19 have disrupted the daily lives of the inhabitants of Quebec, just like the inhabitants of the planet. The pandemic has been accompanied by a continuous flow of information to such an extent that the WHO uses the term ""infodemic"" to describe information overload. This proliferation of information accentuated by social media can have negative repercussions for some people. The surplus of information can generate fear, anxiety, generate mistrust with regard to health authorities, generate dangerous practices that can lead to death, or even non-compliance with preventive practices. Information practices are strongly influenced by the socio-economic level, the level of education, the cultural origin or even the place of residence. Thus, the messages of the public health authorities do not reach certain groups in situations of vulnerability to COVID-19 such as seniors (60 years and +), young adults (18-25 years), members of cultural communities and others. members of indigenous communities living in urban areas. This is why it is important to identify the information practices of these different groups. The results will help guide the communication activities of public health authorities to better adapt to the needs of groups in a situation of vulnerability to COVID-19, thus making it possible to reach them more equitably and promote adherence to the recommended measures.]",2020,2022,Institut national de santé publique du Québec,120870,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older) | Unspecified,Urban Population/Setting | Unspecified,Indigenous People | Vulnerable populations unspecified | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication,2021 +C10712,174885,Feeding EPA and DHA Improve Clinical Symptoms Associated with COVID-19 Infection,"The purpose of this study is to find out if the amount of a certain type of fat in the body, called n-3 fatty acids, is related to the severity of COVID-19 symptoms. Currently, it is known that higher amounts of n-3 fatty acids improve outcomes in some conditions. This study will test whether increasing n-3 fatty acids through a medical food improves the clinical outcomes and severity of COVID-19 infection. Patients admitted to the ICU will be randomized to receive a medical food containing n-3 fatty acids or one without. Blood samples will drawn at specific points during the care of patients who have COVID-19. These blood samples will be examined for fatty acids and level of inflammation. Clinical data regarding symptoms and progression or resolution of disease will be collected from patients medical records. Groups will be compared on level of n-3 fatty acids and the association with inflammation, symptoms and disease progression. We hope this study will lead to simple treatment options involving nutritional strategies designed to significantly raise the individual patient's plasma n-3 fatty acid levels.",2020,2022,University of Alberta,271957.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +C10713,174886,"Chronic pain, poverty, addiction and mental health in a time of pandemic","Canadians are currently facing unprecedented challenges with the COVID-19 pandemic. Governments and health care systems are scrambling to find ways to minimize the downstream impacts of the pandemic on its citizens. However, some groups who experience structural disadvantages as well as certain health conditions, such as chronic pain and poverty, may be finding it more difficult to persevere. Our proposed project will examine how people living with poverty manage their chronic pain during the time of COVID-19. COVID-19 response measures may be creating barriers to accessing services for those living with pain, like pain management services, leading to a spike in overdoses. Our research will also contribute to understandings of how people living with other chronic illnesses (including mental illness and persistent drug use) are variously impacted by pandemic policies, both negatively and positively, and are able to adhere to public health recommendations such as physical distancing and self-isolation. This knowledge will help governments better (re)design our systems and inform decision-making across Canada to ultimately strengthen our public health, health and social care systems now and into the future for all Canadians.",2020,2022,Western University,126913.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C10714,174887,Targeting the novel coronavirus SARS-CoV-2 using an ancient antibody system,"Antibodies are key molecules generated by cells of the immune system involved in the defense against invading pathogens. They are able to bind their targets with a very high degree of specificity. This specific target recognition makes antibodies also valuable reagents in biomedical research as well as in clinical diagnostic and therapeutic applications. While the immune system is capable of generating a vast variety of antibodies, certain targets are difficult to engage either because the protein architecture prevents binding to the target or because the immune system fails to respond to the target. To address this challenge, we propose to harness the variable lymphocyte receptor (VLR) antibody system of the evolutionarily distant jawless sea lamprey. Similar to conventional antibodies, VLR antibodies recognize targets with a high degree of specificity. However, their protein architecture is radically distinct, suggesting that they may detect targets that cannot be recognized by conventional antibodies, a hypothesis supported by studies in our laboratory. We developed an approach to generate specific VLR antibodies. Here we propose to use VLR antibodies to specifically target SARS-CoV-2, the viral pathogen causing Covid-19. Our research will provide a new approach to target the virus, to devise a new class of diagnostic reagent an to explore new vulnerabilities of the viral pathogen.",2020,2022,University of Toronto,181305,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C10715,174888,Predicting perceived and unmet mental health needs in the populations,"COVID-19 is unprecedented in terms of its magnitude and impacts on population mental health and health services delivery. The closure of in-person mental health services may have exacerbated the issues of unmet mental health needs and accessibility. Perceived and unmet mental health needs constitute the central part of demand which is a critical element in the process of health resources allocation. However, we have a little knowledge about perceived and unmet mental health needs at the nation, provincial/territorial, and health region levels, and how the needs may have changed in the context of COVID-19. Building upon our strong expertise in risk predictive analytics and machine learning, we proposed to: 1) estimate perceived and unmet mental health needs pre- and during the pandemic in the populations, and 2) develop innovative tools for estimating and projecting perceived and unmet mental health needs, using both statistical and machine learning approaches. For the objectives, data from the Canadian Community Health Survey and Canadian Urban Environment Research Consortium will be linked and analyzed. The research team involves expertise of psychiatric epidemiology, mental health services research, population health, machine learning, in collaboration with knowledge users from federal and regional health agencies. The proposed study will produce evidence about how the pandemic may have affected perceived and unmet mental health needs, and how the needs vary by demographic, socioeconomic and geographic characteristics, and neighborhood social determinants. We will build predictive models for estimating and projecting perceived and unmet mental health needs at health regional levels, assisting decision makers and mental health service planners in allocating healthcare resources in a timely, equitable and efficient way.",2020,2022,University of Ottawa Institute of Mental Health Research/Institut de recherche en santé mentale de l'Université d'Ottawa,108783,Human Populations | Other,Unspecified,Unspecified,Urban Population/Setting | Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery,2021 +C10716,174889,Sexual Health and STI Prevention For Men Who Have Sex with Men (MSM) In Suburban Cities,"Sexually transmitted infections (STIs) were epidemic in Canada before the COVID-19 pandemic. The ways we usually stop STI epidemics were not working; maybe because we focused interventions on men who have sex with men (MSM) in Toronto's urban downtown, where infection rates are highest, and largely overlooked MSM living in suburban, exurban and rural areas. Many sexual health clinics closed with COVID-19 shutdowns and access to STI testing and treatment became limited. Public health response measures, such as physical distancing and self-isolation, impacted the connectivity of social networks, and by extension, sexual networks. Our goal is to improve sexual health care services for MSM in suburban areas. This requires exploring how MSM from the suburbs manage their sexual lives and sexual health, before and during the time of COVID-19. Specifically, we will: 1. Measure the impact of COVID-19 on the sex life and sexual health seeking behaviours of MSM living in the suburbs. 2. Explore how MSM connect with their social, cultural, racial, ethnic, religious, sexual, and health service communities. 3. Explore how MSM in the suburbs take care (or not) of their sexual health, where they access sexual health services, and how to improve local access and services. 4. Suggest ways to improve sexual health care serving for suburban and rural MSM both independent of, and during, COVID-19. This study is a partnership between the University of Toronto, Moyo Health and Community Services, and Region of Peel - Public Health. We will conduct and online survey and follow-up by interviewing MSM living in Peel Region (Mississauga, Brampton, or Caledon). We will suggest ways to improve sexual health services that respect the different identities, communities, and relationships MSM in suburban areas have to manage. We will host workshops online with community and health care providers to share results, check our interpretations, get feedback, and maximize uptake of results.",2020,2023,Moyo Health and Community Services,311240.25,Human Populations,Unspecified,Adults (18 and older),Suburban Population/Setting,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C10717,174890,The impact of the COVID-l9 Pandemic on long term care home staff and residents,"The COVID-19 pandemic has put enormous additional stresses on Canada's already stressed long-term care system - both the older adults living in long-term care and the frontline workers giving them direct care. Canada has the highest percentage of COVID-19 deaths as a percentage of total country COVID-19 deaths in the world at over 80%. Residents, families, and care staff have been under high levels of stress related to COVID-19 since early spring 2020. Previous reports from the SARS epidemic and early reports from Wuhan, China suggest that the front line staff will experience major mental health challenges and we have already seen early reports of the impact on residents. We will assess the impact of COVID-19 on quality of care and quality of life for residents on mental health and quality of work life for front line staff. We have a large database completed just prior to the COVID-19 spring lock down in LTC homes that includes both residents and staff assessments. In this project, we will collect data one year after the lock downs began to assess the impact of the pandemic. Our findings will be critical to guide improvement efforts in key areas for both residents and staff. We have the networks, partnerships, and proven pathways to bring our findings and recommendations to decision makers who need them and can use them to guide decision-making.",2020,2022,University of Alberta,597943.1,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C10718,174891,Quality of Death in Hospital and Bereavement Outcomes in the COVID-19 Era,"Background: The COVID-19 pandemic and its control measures have changed how people die and how their families grieve. Strict visitor policies in hospitals, restrictions on post-death ceremonies (e.g., funerals), social isolation and lack of access to professional support may have significant negative effects on the quality of death (QOD) of individuals dying during the pandemic and put their family members at risk of experiencing severe grief reactions. It is important to understand how the COVID-19 pandemic has changed the way people die and grieve because this can help improve the support services that are available to families at their most vulnerable time. Aim: This 2-year study will recruit bereaved family members of individuals who died of any cause in two hospitals in Toronto, Ontario, in order to evaluate: i) the QOD and bereavement outcomes (depression, post-traumatic stress and complicated grief) and who is at a greater risk for worse QOD and more severe grief reactions; and ii) the experience and perceived met and unmet support needs of bereaved family members. Methods: Six months after the patient death, family members of patients who died at the University Health Network or Sunnybrook Health Sciences Centre will be asked to complete surveys of the patient's QOD, their satisfaction with and access to care, depression, post-traumatic stress and grief reactions. Participants will also be interviewed about their experience of death and grief. Our research team has experience in interviewing and surveying family members after the death of a loved one in a sensitive and respectful manner. Relevance: It is urgent to address the impact of the pandemic on grieving Canadians. Our study will provide real-time evidence to inform policy and clinical guidelines to better support family members before and after patients' deaths and develop interventions to prevent and treat complicated grief and to support bereavement in general during the pandemic and beyond.",2020,2022,University Health Network,232674.75,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C10719,174892,COVID-19 and Precarious Employment (COPE),"With the COVID-19 induced economic downturn, workers with precarious employment have experienced large negative impacts on financial well-being. While the federal government has responded with financial assistance for workers, precarious workers are eligible for too few of these benefits. In this study, we will measure the impact of the COVID-19 crisis on the health and well-being of precarious workers in Ontario and their families/households. We will also determine to what extent they experienced relief from workplace and government assistance emerging in response to the pandemic. We will answer two research questions: 1.How have government and workplace policy responses in the wake of the COVID-19 virus supported or neglected workers with the highest precarious employment conditions in the first three years of the pandemic? 2.How have the first three years of the COVID-19 economic and health crisis affected employment conditions, health and well-being, and access to resources and health care for workers with the highest precarious employment conditions and their families/households? In this two-year longitudinal study we will administer short 15-minute online surveys to up to 500 individuals with precarious employment. We will conduct longer in-depth 90 minute qualitative interviews with 60 individuals with the high levels of precarious employment. To answer our research questions we will have 3 waves of quantitative surveys and 2 waves of qualitative interviews to monitor changes in conjunction with the evolving pandemic. We will complement these participant interviews with an analysis of ways in which workplace and government emergency responses have succeeded or failed to meet the needs of precarious workers. Our research advances the science of precarious employment and public health and also flags crucial policy gaps experienced by those with precarious employment over the first three years since the start of the pandemic.",2020,2022,Unity Health Toronto,238718.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C10720,174893,Imaging Neuroinflammation In COVID-19 and Persistent Depression With/Without Other Neuropsychiatric Symptoms,"COVID-19 is infecting 1 in 100 Canadians and over 23 million people around the world. After people recover from short term breathing problems, and feelings of sickness with the virus, there can be longer term problems affecting the brain. It is believed that the virus can cause inflammation of the brain. We know that inflammation in the brain is implicated in causing depression symptoms. About 30% of those infected with COVID-19 report later elevations in level of depression and/or other symptoms of mental illness. The purpose of this study is to use state of the art brain scanning to detect whether brain inflammation is happening in those with COVID-19 who later get depression and/or other mental illnesses. There are two main purposes for this study. First, it would be the first to show definitive evidence of brain inflammation in COVID-19 with later mental illness. Second, if we discover brain inflammation, we can study treatments to see if they can prevent or remove this inflammation, using the brain scan to show that the treatment has an effect in the brain. Having a brain scan to detect COVID-19 effect in the brain is extremely important for developing new brain treatments for COVID-19: Most companies and many government funding agencies like the National Institutes of Health in the US, require use of brain scanning to show that brain treatments get into the brain as a requirement to invest funds for clinical trials.",2020,2023,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,601328.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C10721,174894,"CO-Away: Implementation and Evaluation of Digital Health Solutions for Indigenous Self-Determination, Governance, and Data Sovereignty","During wave 1 of the COVID-19 pandemic, northern Indigenous communities in Saskatchewan experienced a rapid surge of COVID-19 cases, with the highest number of active cases in the province at a time when the rest of Saskatchewan was showing signs of recovery. This is an indication that the timeline of outbreak waves in remote Indigenous communities differs from larger population centres. More distressingly, while the rate of infections in remote Indigenous communities was projected to rise sharply, other parts of the country were already planning to reduce restrictions - reiterating the history of disjointed and bifurcated policy towards Indigenous Peoples. The 1918 influenza pandemic swept across the frozen lakes and boreal forests to devastate communities in the north. 100 years later, the risk to remote Indigenous communities is still high, especially because inadequate housing and overcrowding increase COVID-19 transmission. To address this risk, we have developed CO-Away, a culturally-responsive digital epidemiological platform to monitor, mitigate, and manage Coronavirus disease (COVID-19) outbreaks. CO-Away's purpose is to serve Indigenous communities and enable Indigenous self-governance, determination, and data sovereignty. CO-Away will be launched in Ile-a-la-Crosse, a subarctic northern community in Saskatchewan. The CO-Away platform consists of two key components - a frontend virtual care smartphone application (app), and a backend digital decision-making dashboard. The app provides three key precision medicine services that are specific to each citizen: 1) continuous risk assessment of contracting COVID-19 via the virtual doctor feature; 2) evidence-based public health communication; and 3) Citizen reporting of food availability, access to public services, and COVID-19 symptoms and test results - these culturally-responsive features have been co-created with Ile-a-la-Crosse Metis decision-makers based on imminent community needs and preferences.",2020,2023,University of Regina,438002.86,Human Populations | Other,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Social impacts | Other secondary impacts,2021 +C10722,174895,Making Visible the Life Stories of Families of Children who are Immunocompromised during COVID-19,"A significant number of children worldwide are immunocompromised (IC). These children are extremely vulnerable to illnesses and infections, meaning that any time IC children or their family members leave their home, the child's life is in jeopardy. Families of IC children encounter many challenges and inequities, such as financial difficulties, poorer physical and psychological health, social isolation, and marginalization. In spite of the large number of IC children, we have little understanding of what it is like to be a family of an IC child. Moreover, we have limited understanding of these families' experiences during the current COVID-19 crisis from the emergence of the virus, to the various peaks and waves, to the new and changing circumstances in which they find themselves trying to adjust as part of their everyday lives. The goal of this 4-year patient-oriented study is to understand and document the lived experience of families of IC children during COVID-19. Children under the age of 18 who are IC (primary or secondary) and their families (including parents, caregivers, siblings) across Canada will be invited to take part in the study. Multiple data sources are planned to include individual and family interviews (conducted in English and French), and digital story-telling. Short-term, the study will result in advanced knowledge on the experiences of families of IC children during COVID-19 including insights into their well-being has been affected by the pandemic. Recommendations to improve healthcare and social supports and services that improve their well-being for future waves and/or crises will be identified. Long-term, the work emerging from this research program will be used to inform patient-oriented service delivery and outcomes nationwide for this currently underserved and vulnerable population, with implications for children who are IC and their families residing in other contexts, important for future pandemics and other public health crises.",2020,2023,University of Manitoba,283289.26,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C10723,174896,Impact of Aerosol Box Use on Patterns of Healthcare Provider and Environmental Contamination during Aerosol Generating Medical Procedures: A Multicenter Study,"Many patients diagnosed with Coronavirus Disease 2019, or COVID-19, suffer from severe illness requiring intensive medical care. The sickest patients often require procedures, called aerosol-generating medical procedures (AGMPs), that spread virus throughout the air. When doctors perform these procedures they are at high risk of getting sick with COVID-19. A new device, called an aerosol box, has been invented to protect healthcare providers while they perform AGMPs. This device is placed over top of the patient's head while they are lying on a stretcher, shielding the doctor's face from viruses in the air. Unfortunately, there has been no research done describing how well the aerosol box works to protect doctors, nurses and respiratory therapists. Our study will use a plastic manikin head and chest as a patient. Teams of doctors, nurses and respiratory therapists will work together to perform AGMPs on this manikin. We will put a special powder in the manikin's mouth. When the doctor's perform their task, the powder will be spread throughout the air, just like a virus. Then we will use a camera and UV light to see where the powder has spread. Half of the teams will use the aerosol box, and the other half will not, which will allow us to determine if it is effective at preventing spread. By seeing where the powder has spread, we will also be able to figure out how risky each type of AGMP is for doctors, nurses and respiratory therapists. At the same time, we will measure how long it takes for them to complete the procedure. This is important because it will help hospitals decide if aerosol boxes should be routinely used when caring for COVID-19 patients. Our study will also help hospitals develop rules to reduce healthcare provider risk when performing AGMPs during the COVID-19 pandemic.",2020,2022,University of Calgary,196413.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2021 +C10724,174898,Repurposing an FDA-approved anti-gout drug for the treatment of COVID-19,"The ongoing pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 has posed an unprecedented health and economic threat worldwide. Despite the intense research since its outbreak, there is currently no effective treatment or vaccine for this disease. This project focuses on the development of a novel therapeutic for COVID-19 by drug repositioning. Probenecid, under the brand name Probalan, is a medication that is primarily used in treating gout by increasing uric acid excretion in the urine. We have recently made exciting observations that probenecid potently inhibits infection of two different but related families of RNA viruses, i.e., corona- and entero- viruses. Moreover, unlike some anti-viral drugs that may cause severe cardiotoxicity, probenecid actually reduces cardiovascular risks associated with decreased inflammatory response. Based on these preliminary data and the proven anti-inflammatory role of Probenecid, we postulate that Probenecid is a very attractive drug candidate for COVID-19 treatment by suppressing SARS-CoV-2 replication and alleviating disease-associated systemic and lung inflammation. To test this hypothesis, we propose two aims: (1) evaluate the potential of repurposing Probenecid for COVID-19 treatment using cell and mouse models; and (2) define the underlying anti-viral mechanism of Probenecid. If successful, the significance of this study and the follow-up clinical trial will be huge for patients with COVID-19.",2020,2023,University of British Columbia,444197.25,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C10725,174899,Digestive endoscopy in the era of COVID19: An opportunity for optimizing timely equitable care during the pandemic and beyond,"Digestive endoscopies are amongst the most frequently practiced procedures, allowing for specialized endoscopic therapy and permit diagnosis and treatment of pre-cancerous lesions in the upper and lower GI tracts as well as further oncological management. The SARS-coV-2 pandemic has dramatically impacted on endoscopic volumes across Canada; most units saw a sudden reduction of almost 90% of endoscopies with a resulting unmanageable increase of postponed exams since the first pandemic wave hit that persisted even after activity resumption. Amalgamating data from five centers, a ""best-case"" scenario suggests 30,757 procedures (35% of usual yearly totals) will NOT be performed; with a worst-case scenario reaching 69,301 over the 12 months following the initial COVID outbreaks, depending on pandemic epidemiology, mitigation protocols, resources shortages, and patient apprehension about attending a procedure. The crisis is compounded by a paucity of evidence-based forecasting and few procedural priority setting instruments. We propose to establish a toolkit for GI endoscopy units across Canada, addressing these issues by developing and validating clinical and resource management instruments. We will create a dataset of almost 90,000 procedures, designing validated referral prediction for gastroscopies and colonoscopies, allowing for a credible, standardized and equitable approach for triaging these procedures into hierarchal groups. Data collection will be facilitated by implementing a national learning process-based AI platform, while predictive modelling will be validated employing machine learning. We will also use AI methods to optimize procedural scheduling that varies widely across the country. The proposed deliverables develop, test, and implement effective approaches to manage the consequences of COVID-19 at individual and population levels by creating generalizable instruments that amplify existing research platforms and AI infrastructure.",2020,2022,McGill University Health Centre/Centre Universitaire de Santé McGill,619458.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C10726,174900,Burden of COVID-19 among people living with HIV in Ontario,"The COVID-19 pandemic has shown that certain members of our society may be at higher risk for severe disease. One such group is people living with HIV. HIV affects the immune system's ability to respond to infections and shares some of the same risk factors as COVID-19, such as older age, comorbidities, and lower income. So far, people living with HIV who are taking medications to control their HIV infection seem to get infected with COVID-19 and become hospitalized at similar rates to the general population, but evidence in this area is mixed and more research is needed as the COVID-19 pandemic continues to evolve. Because of limited testing and surveillance gaps, we do not yet know how many people living with HIV have been infected with COVID-19 or whether they will have more severe illness than people who do not have HIV. We will use an existing study of about 4,000 people living with HIV who are receiving care in Ontario to fill these gaps. People living with HIV will be invited to collect a finger prick of blood at home. Blood samples will be tested for antibodies to SARS-CoV-2, the virus that causes COVID-19, to see how many people have been infected since the start of the pandemic and whether these antibodies will protect against re-infection. Through linkage to laboratory, hospitalization, and death certificate records, we will find out how many people living with HIV have a lab-confirmed COVID-19 diagnosis or develop more severe illness from COVID-19. We will compare these findings to HIV-negative individuals in Ontario. Through linkage to doctor's visits, we will see how the COVID-19 pandemic has impacted medical care for HIV. Finally, if a COVID-19 vaccine becomes available during our study period, we will also measure vaccine uptake and antibody response to vaccination. These findings will inform health care and health services planning for people living with HIV.",2020,2023,Unity Health Toronto,607371.75,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility,2021 +C10727,174901,Deciphering immune responses in COVID-19 patients to identify immune correlates of protection and susceptibility for targeted therapeutics,"COVID-19 pandemic has already infected >30 M people, claimed >0.9 M lives and paralyzed economies globally. Despite the prior work on understanding how the virus impacts the immune system many questions have remained unanswered and, therefore, substantial efforts are urgently needed to understand them. We yet to understand immune correlates of recovery and protection from COVID-19 infection. Rationally design and evaluate novel vaccines and immunotherapies require a deeper understanding of how the virus interacts with the immune cells. Therefore, we plan to conduct a comprehensive study in detail at the cellular and molecular levels in COVID-19 patients with asymptomatic, mild, moderate, severe, and critical disease in our well-established longitudinal cohorts. We have already assembled a team of internationally-recognized immunologists, virologists, pulmonary medicine, intensive care and infectious disease experts to jointly address some of these issues.  Main Objective: To define protective and long-lasting immunity against SARS-CoV-2 and delineate detrimental immunopathology in COVID-19 by undertaking in-depth immunological studies combined with viral studies and clinical data from the natural SARS-CoV-2 infection across different patient groups. Detailed analyses of immune correlates of protection have the potential for a major impact, especially for those at risk from severe COVID-19. At the conclusion of this work in 3 years, we expect to have gained a thorough understanding of immune responses associated with the patient recovery and severe disease caused by SARS-CoV-2, especially in high-risk groups; fundamental for informing public-health policies needed to limit disease spread and protect high-risk groups.  Feasibility: Collectively, we have established the required breadth of expertise and cutting-edge techniques for COVID-19 research, as shown by our recent under review publications (Nature Communications x2).",2020,2023,University of Alberta,846090,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C10728,174902,Developing and evaluating an online intervention to improve the uptake and maintenance of protective behaviours against COVID-19 among young adults in Canada,"COVID-19 is a worldwide pandemic, and currently no vaccine exists. Thus, many public health officials have recommended physical distancing and wearing masks as key personal protective behaviors to prevent unnecessary deaths and reduce burden on the healthcare system. However, these behaviours can be difficult to adhere to, and the general public may be asked to do them for a long time. Messages from public health officials tend to use an inconsistent approaches that are not based in established theories that explain how to help change people's behaviour. The purpose of this project is to create a program designed to motivate people to physically distance and wear masks by helping them feel that these COVID-19 protective behaviours are tied to a greater societal goal that is larger than themselves and that they are capable of successfully performing them. Motivating people in this way may be more successful in the long run than by relying on fear alone. We plan to create a brief, single-session, interactive online program that understands people's physical distancing and masking behaviour and, based on their responses, provides feedback in real time to either reinforce people's motivation or guide them to consider potential sources of motivation through thought-provoking questions. At the end of the session, people will be provided with a personalized statement of commitment that they can share on social media. We have decided to target young people, who are more likely not to adhere to public health recommendations surrounding COVID-19. The program will be created based on the experiences of a diverse sample of Canadians, will be improved based on user feedback, and will be available in French and English. If effective, a program that could increase motivation for physical distancing and wearing face masks that is relevant and accessible to as many Canadians as possible may help us navigate the COVID-19 pandemic faster and more safely.",2020,2022,University of Calgary,214544.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C10729,174903,"The association between COVID-19-related attitudes, concerns and behaviours in relation to public health policies: A behavioural science approach to optimising policy strategies to improve health, economic and quality of life outcomes (the iCARE Study).","The key to halting the rapid spread of COVID-19 and 'flattening the curve' is public adherence to drastic, rapidly evolving behaviour-based prevention policies that are being implemented around the world. However, adherence depends on: public awareness of prevention policies; the extent to which the public perceives these policies as relevant and important; and their capability to enact them, which may be influenced by various demographic, family, occupational, health, and environmental variables. Further, as things start to re-open, people's willingness to adhere to new government decisions and recommendations (e.g., re: school openings, store openings) will also be critical for transitioning through the phases of the pandemic and improving the economy. Unfortunately, policies have varied greatly between provinces and countries, contributing to uncertainty about government policy motives and confusion about which policies to follow. Understanding people's concerns about COVID-19, their perceptions, beliefs, and attitudes about public health policies, and how they impact what people are (and are not) willing to do will be important for informing policy strategy and communication, to ensure the best health and economic outcomes. The iCARE Study will capture key data on people's awareness, attitudes, and behaviours as they relate to the COVID-19 policies, as well as, the impacts that COVID-19 is having on people's physical and mental health, financial situation, and quality of life. Data from approximately 150,000 people around the world will be linked to case data, policy data, and Google mobility data to understand what government policies are (and are not) influencing behaviour and outcomes, and in whom these policies are most or least effective. This will allow us to inform governments on the efficacy of policy measures on both people's behavior, and on key health and quality of life outcomes.",2020,2022,Université du Québec à Montréal,504632.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C10730,174904,Discovery of small molecules targeting SARS-CoV-2 frameshifting using a rapid yeast platform,"The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to the COVID-19 pandemic worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established drug/vaccine treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Identifying and targeting essential mechanisms that are unique to SARS/MERS-CoVs are key to identifying new antiviral compounds and it is likely a combinatorial approach that targets specific steps of SARS-CoV-2 will be needed (similar to antiviral cocktails for HIV and HCV). The goal of this proposal is to rapidly identify novel drugs targeting a unique mechanism in SARS-CoV-2, called -1 frameshifting. The approach will use a rapid yeast platform which has been used successfully to identify drugs that target autophagy, cell-cycle and influenza. Our entire pipeline will identify non-toxic, bioactive compounds that enhance or inhibit -1 frameshifting that will be tested for efficacy in blocking SARS-CoV-2 infection. The identification of small molecules that inhibit or enhance SARS-CoV-2 FS activity will contribute to candidate therapeutic approaches to treat COVID-19 disease and potentially future emerging outbreaks.",2020,2023,University of British Columbia,351731.7,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C10731,174905,The Effect of COVID-19 Policies on Road Traffic Injury Among Vulnerable Road Users in Canadian Cities,"An unexpected benefit of the COVID-19 pandemic has been a temporary, dramatic reduction in road traffic injuries. Pandemic-related stay-at-home and physical distancing policies led to great reductions in police-reported collisions during the early stages of the pandemic. However, with the progression of the stages of re-opening, reports of collision fatalities have been emerging, likely due to reported increases in speeding. We will assemble collision data from March 2017-April 2023 in 4 Canadian cities - Toronto, Montreal, Calgary and Vancouver and across provinces. The objectives are to 1)determine the effects of the implementation of COVID-19 'stay home' and physical distancing policies on rates of road traffic deaths and injuries 2) determine the effects of relaxation of COVID-19 'stay home' policies (while maintaining physical distancing policies) on rates of road traffic deaths and injuries 3)determine the effects of specific COVID-19 related local roadway mitigation strategies on road traffic injuries and deaths (e.g. lane closures, new bicycle lanes). Collisions and specific new local road safety strategies, such as bike lanes and road closures will be mapped. Collision rates before the implementation of stay-at-home and physical distancing policies, during implementation, and after the relaxation of policies will be compared as well as before and after the implementation of specific road interventions. Data will be analyzed by age, sex, injury severity and travel mode. Cities now have a critical opportunity to institute policies to create safer walking and cycling environments. This pan-Canadian team brings decades of experience having collaborated on applied interdisciplinary research related to active transportation, motor vehicle collisions, road safety policy and the built environment. Results will be shared and disseminated through a variety of key stakeholders including; the municipalities and Parachute, the national injury prevention charity.",2020,2023,Ryerson University,329370.75,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C10732,174906,Short and Long Term impact of COVID-19 on mental health and wellbeing of health workers in Pakistan,"As COVID-19 continues to spread, there is growing concern about its impact in low-and middle-income countries like Pakistan. Like other western countries, Pakistan is experiencing sudden rises in the number of positive COVID-19 cases. Should the virus spread unabated, the impact could be extreme in Pakistan given its fragile economy, limited healthcare access and resources, widespread poverty, gender inequality, and poor health outcomes. As with previous disasters, epidemics and pandemics, preliminary studies from North America, Europe, and Asia show an increased occurrence of depression, anxiety, insomnia, and distress among health workers and the general public in the wake of COVID-19. Yet there has been little research to understand the impact of the pandemic on the mental health and wellbeing of health workers in Pakistan. The overall goal of this study is to assess and promote the mental wellbeing of health workers affiliated with the Aga Khan University Hospital (AKUH), Pakistan. This study will include all HWs (from health care providers and support staff to administrators). The proposed study will consist of: (1) a baseline survey to assess the mental health and wellbeing of HWs, (2) development and dissemination of targeted resources to support wellbeing of HWs, (3) assessment of longitudinal changes in mental health burden of HWs, over a 6, 12, and 24 month period, and (4) evaluation of the use and uptake of resources provided. Results and lessons learned will be shared with local and global communities and leaders in an effort to mitigate the negative impacts of COVID-19 on the mental health of health workers.",2020,2023,University of British Columbia,238718.25,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Eastern Mediterranean,Eastern Mediterranean,,,,Pakistan,Pakistan,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C10733,174907,Upstream determinants of effective COVID-19 response: tools development and application through a case study in British Columbia,"In the midst of an acute crisis, researchers and governments have properly focussed on responding urgently to a rapidly evolving situation. This has resulted in a focus on interventions, their implementation, and their effectiveness. But the diverse experience of many countries suggests to us that there are critical ""upstream"" factors that need to be better understood and planned for to increase the likelihood of more positive outcomes. We refer to these factors as the institutional, organizational, governance, and political dimensions of the response to COVID-19 or ""IOGP"" for short. The effectiveness of current and future responses to pandemics can be improved by learning about and documenting better and worse practices in relation to IOGP both retrospectively and prospectively in the current crisis. This proposal will support the development of tools for analyzing IOGP factors and their application in a case study linking IOGP factors to policy responses to COVID-19 in British Columbia. An interdisciplinary team of researchers at the University of British Columbia has formed to study how IOGP factors influence the effectiveness of jurisdictional responses to COVID-19 across Canada. We have launched an initial pilot study, developing a theoretical framework, methods and instruments for data collection including comparative timeline, organizational mapping, and key event interview guides. This project will support further development of the definitions, concepts, methods, and measures that can be used to study these upstream factors and their implementation in BC and other provinces with local partners. The results will be used to identify better and worse practices in relation to laws, regulations, organizations, and political and governance processes that improve pandemic response. Better practices can inform different contexts in Canada and globally.",2020,2022,University of British Columbia,93674.25,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health leadership and governance,2021 +C10734,174908,Bicyclist and pedestrian crashes in Ontario: Detection and comparison of health outcomes between police-reported collisions and injury health care records,"Active transportation modes like walking and bicycling have environmental and health benefits. The COVID-19 pandemic has placed a new focus on active transportation as a ""safe"" (physically-distanced) travel option. But people walking and bicycling are more vulnerable to road injury. Studies of bicycling and pedestrian injury often rely on police-reported collisions data. However, not all walking and bicycling road injuries are reported to police or entered into collisions records, especially when motor vehicles are not involved or where their involvement is indirect. Police-reported collisions data also contain minimal information on outcomes following injury. Health care records can help detect additional road injuries and the outcomes of these injuries for bicyclists and pedestrians. This project will learn from a linkage between reported collisions and health care records of bicycling and pedestrian injury in Ontario in 3 ways: 1) Ministry of Transportation (police-reported) collision records will be linked to records of health care use (emergency department visits and hospital stays) to compare bicycling and pedestrian collisions reported to police and those found in health care records. We will examine how characteristics that are individual (e.g. gender, age), neighbourhood (socio-economic status), and regional (rurality) affect the chance of being detected in both reported collisions and health care records. 2) We will annually update the linkage as new data become available, including the time period of COVID-19. 3) We will look at what happens to injured pedestrians and bicyclists after crashes, comparing collisions reported to police and those found in health care records, by following their hospital and physician visits after injury. This study will build new partnerships between road safety surveillance and epidemiologists, and form groundwork for prevention of active transportation injury in Canada.",2020,2023,Ryerson University,256848.75,Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C10735,174909,Brain Injury Pandemic Preparedness: Optimizing Community Strategies,"This study will examine how community brain injury associations have changed their services to meet the needs of Canadians affected by brain injury and how to further improve services. Over 1.5 million Canadians live with chronic brain injury. After a brain injury, people often struggle to meet basic needs and stay healthy. Even before the pandemic, life was hard for people living with brain injury. They may have had difficulties in moving or thinking; had mental health issues; or been in pain or always tired. The Covid-19 pandemic has made living with brain injury worse. Many people are reporting increased brain injury symptoms due to stress, isolation, routine disruptions, and less supports. They are struggling to understand and follow public health information to stay healthy and keep others healthy. To meet these increased needs, community brain injury associations provide crucial supports and services. During the pandemic, these associations have had to quickly change their services and the way they provide them, with little guidance from public health. This project will use online information sharing meetings for staff and volunteers of brain injury associations across Canada to improve community services during pandemics. Experts in brain injury research and services will analyse and summarize the information from sharing meetings and present it back to the brain injury associations. This study will help the community associations work together and co-develop a helpful online tool to improve how they support people living with a brain injury during a public health crisis. By getting Canadian brain injury associations collaborating with each other, this project will develop an online resource that can be used to improve their services during this pandemic and in their preparations for future public health crises. The aim of this project works toward the CIHR goal of making community and social care action plans to improve the health of vulnerable people.",2020,2022,Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal/Centre de rech interdisciplinaire en réadaptation du Montréal métropolitain,172239.75,Human Populations,Unspecified,Unspecified,Unspecified,Other,Hospital personnel | Volunteers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C10736,174910,Developing a novel vaccine against COVID-19,"The emergence of life-threatening human respiratory viral pathogens such as SARS-Cov, MERS, and current SARS-Cov-2 present an intense challenge to clinicians who are left with no available therapeutic interventions and scientists who must rapidly develop novel therapies in the midst of a pandemic. Individuals with COVID-19, the disease caused by SARS-Cov-2, exhibit a range of symptoms ranging from mild cough to acute respiratory failure. While most SARS-CoV-2-infected individuals develop only mild disease, infection can be fatal in vulnerable populations, including the elderly. Although the global scientific community is working together to find treatments to stop the outbreak, there are currently no therapeutic approaches that prevent or mitigate SARS-CoV2 infection. Clearly, developing a vaccine that improves the early immune response to infection and prevents disease progression is required to end this pandemic. The goal of our studies is to establish new vaccine approaches to prevent SARS-CoV-2 infection or minimize disease sequelae. Using preclinical animal models, unique clinical human samples collected from COVID-19 patients or individuals with specific vaccination histories, we will test the efficacy of our vaccination strategies against virulent SARS-CoV-2 infection. Within this framework, we will use two major complementary approaches to enhance immunity against COVID19. Our studies will provide new insight into how we can harness the power of our immunity to improve vaccines and human health. If successful, these vaccine strategies can be rapidly deployed to the general population to bring an end to this and potentially future COVID-19 outbreaks.",2020,2023,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,450240.75,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C10737,174911,"Impact of COVID-19 restrictions on Ontario long-term care and retirement home residents' health, well-being and function","Background: To limit spread of COVID-19, long-term care (LTC) and retirement homes restricted residents from leaving homes and family members from entering. Many settings also limited movement of residents within homes. These restrictions were a logical approach to attempt to limit spread of the virus; however, they had serious consequences for the health, well-being, function and autonomy of older adult residents, and important implications for family members and staff in the facilities; these consequences have not been methodically examined. Objectives and methods: Using quantitative and qualitative methods we will 1) conduct a survey to detail and categorize levels of pandemic restrictions in LTC and retirement homes across Ontario; 2) use mobile device data to explore actual movement patterns in these settings; 3) access provincial COVID-19 data to trend outbreak and infection rates with changes in movement restrictions; 4) track outcomes related to health, well-being and function (e.g. RAI-MDS scores for function in activities of daily living, cognition and mood for LTC residents; frailty scores and disease profiles for LTC home residents) to measure the impact of movement restrictions on the well-being, health and function of Ontario LTC home residents; and 5) conduct qualitative interviews to describe the experience of movement restrictions and implications for residents, family members and LTC and retirement home staff. These data and methods will enable us to identify the impact of restrictions on health, well-being and function in the short and longer term. Impact and expected outcomes: This is the first study examining the impact of restrictions in LTC and retirement homes on residents' health, well-being and function, and implications for family and staff. This novel and highly relevant study will provide much needed knowledge to inform practice in LTC and retirement care homes to reduce potential harms in this and future pandemic situations.",2020,2022,McMaster University,90850,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Approaches to public health interventions,2021 +C10738,174912,Palliative care at the end of life among patients with cancer before and during the COVID-19 pandemic,"The COVID-19 pandemic has had a large impact on cancer care, resulting in restrictions to hospital and community services as well as to inpatient visitors. Although palliative care has been shown to improve outcomes for patients with cancer, there has been no large-scale study on how the COVID-19 pandemic has affected the delivery of palliative care. Our aim is to understand the impact of the COVID-19 pandemic on the use of palliative care services at the end of life for patients with cancer. We will conduct this study in two parts. In Part 1, we will use Ontario's healthcare data, which are routinely collected for all patients receiving healthcare in hospitals (as outpatients, inpatients or in emergency rooms) or at home. Using these data, we will compare palliative care near the end of life (e.g. whether, when, and how often a palliative care service was involved in the patient's care) as well as acute care use in the last month of life (e.g. attending the emergency department or hospital admissions) before versus during the COVID-19 pandemic. We will also determine if any changes in receiving palliative care services before versus during the COVID-19 pandemic are greater among patients from areas of Ontario that are more affected by poverty. In Part 2, we will use individual and group interviews to understand the perspectives and experiences of bereaved family caregivers and healthcare workers regarding access to palliative care at the end of life for patients with cancer who died during the pandemic. We will use these results to complement and explain our results from healthcare data. Our research team includes experienced researchers, clinicians and policy-makers, in order to ensure that the results of our research are incorporated into practice. This project will help inform strategies to improve the delivery of palliative care for patients with cancer during and beyond the ongoing COVID-19 pandemic.",2020,2023,Princess Margaret Cancer Centre,334205.55,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C10739,174913,Coping strategies and mental health: quantitative and qualitative insight into the COVID-19 experience in young adults,"Accumulating evidence suggests that COVID-19 is affecting mental health and well-being, and that young adults are hardest hit. Not addressing this issue could have important impact on the ability of young adults to ""pick up where they left off,"" especially if this increased vulnerability erodes their enthusiasm, hope and resiliency to fully re-engage post-pandemic when doing so is critical for their families, society and the economy. Yet fundamental evidence that could inform policy and programming in Canada is lacking, including descriptions on how mental health has evolved among Canadians during COVID-19, better understanding of coping strategies used by young adults to deal with COVID-19 stress (i.e., substance use, physical activity, screen time, online support groups, reliance on social media), whether these coping strategies helped, and identification of specific higher-risk subgroups of young adults that need help the most (e.g., mothers balancing telework with childcare; heads of households who lost their jobs; vulnerable young adults unable to access mental health services). To address these gaps, we will leverage data from two well-established cohorts of young adults in two provinces with very different COVID-19 experiences (NDIT in Quebec; MATCH in New Brunswick). NDIT has pre-pandemic data in 24 data collections spanning age 12 to 33 (1999- 2020). MATCH has 25 data collections spanning age 9 to 20 (2011- 20). More specifically, we will use pre- and early pandemic data in combination with newly collected quantitative and qualitative data in Fall 2021 and Fall 2022, to monitor trends in mental health and coping strategies in both cohorts. Qualitative data on the pandemic lived experience will be collected in 85 one-on-one interviews. These data, combined with ongoing consultations with our knowledge users, will inform discussion on developing, repurposing, and scaling up mental health interventions targeting young adults during pandemics.",2020,2022,Centre hospitalier de l'Université de Montréal,361363.38,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C10740,174914,"The Canadian Severe Acute Respiratory Infection, Prospective, Perpetual Observational Study: Informing Clinical Care and the Public Health Response","Severe acute respiratory infection (SARI) is a major public health problem. The commonest cause of SARI is influenza which is responsible for substantial illness and death each year, in addition to outbreaks and periodic pandemics. Recent outbreaks of pandemic influenza viruses and coronaviruses such as COVID-19, have taught us not only that these viruses can lead to severe illness and death, but also that it can take a long time between the start of an outbreak and when the health care system knows enough about the illness to guide public health policy and clinical care. Each year since 2016, with a network of hospitals and infectious diseases and critical care clinicians, we have described severe respiratory infection in Canadian hospitals, the viruses and bacteria that cause people to get sick, their treatments and how often it leads to patients needing critical care or dying. When the COVID-19 pandemic hit, this team of over 50 adult and children's hospitals worked in collaboration with the World Health Organization and partners in other countries to describe severe illness from this new virus. We found that patients were typically older, more commonly men and often had pre-existing medical problems. Of patients who were sick enough to need admission to the intensive care unit, about one-quarter unfortunately still died; however, this is a much lower death rate than in many other countries hit hard by the pandemic. This ongoing study will describe whether patterns of illness change in the second and subsequent pandemic waves, and will provide a way to rapidly study common and new respiratory infections in the future to inform policy and practice.",2020,2023,Sunnybrook Research Institute,359588.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2021 +C10741,174915,Mitigating the Effects of Epidemic/Pandemic Outbreaks on Temporary Foreign Agricultural Workers and Farm Operations in British Columbia,"Temporary foreign workers (TFWs) employed for seasonal agricultural work play a vital role in preserving Canada's food security. However, TFWs are known to experience many health and structural inequities such as occupational health hazards, inadequate hygiene, and barriers to health services. Often they accept these conditions for fear of losing their jobs. This situation was made worse during the COVID-19 outbreak. Federal and provincial government agencies subsequently announced several programs to safeguard TFWs and relieve the burden on farmers. Our research will determine the COVID-19 experiences of TFWs and farming operations in British Columbia during the 2020 season. We will also assess whether workers and farmers think the government programs to safeguard them from COVID-19 were effective in controlling disease transmission and making it easier to continue farming operations in both 2020 and 2021. We will do this research by interviewing 40 TFWs and 20 farm owners who employ TFWs for seasonal agriculture work in the Fraser Valley area of British Columbia, as well as 8 members of BC agricultural councils. This research is being conducted by researchers from the University of the Fraser Valley who have extensive experience in working with immigrant populations and infectious disease, community health and qualitative methods. The inclusion of appropriate Knowledge Users (including the BC Provincial Health Officer, BC Centre for Disease Control, BC Agricultural Council, regional health organizations and community organizations who provide assistance to TFWs) will ensure the research meets their needs and is conducted appropriately and respectfully. Their involvement also means the results can be readily mobilized into practice. The results from our research will be used to develop recommendations to continue to reduce the inequitable burden of disease for this population now and in the future, and to ensure food security for Canadians.",2020,2022,University of The Fraser Valley,274979.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C10742,174916,"Restricted family presence in the PICU during the COVID-19 pandemic: Understanding impact, experience, and stakeholder priorities","Family presence is essential to family centred care in pediatric intensive care units (PICUs), where children have a high risk of death and disability. PICUs generally value and promote family presence. But to minimize COVID-19 spread, hospitals and PICUs implemented policies to restrict family presence. Our research team, consisting of healthcare providers (HCPs), families, patients, and policy-makers has been studying the policies and their impacts. We have found a lot of variability in the policies and evidence of harm to all stakeholders. We have not yet studied the impact on children. Before the next major threat to family presence and family centered care, we need input from patients, families, and HCPs on what is most important to them in family presence policies, what the impact of restrictions are, and what important outcomes of a family presence policy are. In this study we will build on our existing work and use the situation of restricted family presence to frame a better understanding of family presence policies in general. We will interview pediatric PICU patients to better understand the impact and experience of these policies, and also which parts of a family presence policy are important to them. Next, we will hold focus groups with patients, families, HCPs, and administrators where we will work together to develop priorities for family presence policies, identify ways to improve or avoid the impact of restricted presence policies, and determine how to best assess these policies. Finally, we will hold a national stakeholder conference to create consensus statements on family presence in PICU. All of our studies have been designed with Patient Partners and people in healthcare who will use the information, and we will exchange information with people affected by family presence policies throughout the studies. We will use national platforms to disseminate consensus statements and we will look for feedback from patients, families, and HCPs.",2020,2022,IWK Health Centre,262892.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery,2021 +C10743,174917,Social Isolation and Cognitive Function in Middle-aged and Older Adults: A Prospective Analysis of the Canadian Longitudinal Study on Aging,"Social interaction and cognitive function are critical to aging well. As humans are social beings, social isolation may worsen mental health conditions, lower quality of life and access to health services, and lead to adverse health outcomes. Poor cognitive function reduces independence and quality of life, and increases the chances of developing dementia, being institutionalized, or dying. Scientists believe social isolation can lead to poor cognitive function. However, the links between social isolation and cognitive function are not well understood. To understand these complex links, we will use data collected from more than 27,000 Canadians aged 45 to 85 years. These data include social, psychological, demographic, and health information collected at two points in time, spread three years apart. The collection of these data is made possible through a large investment from the federal government. Using this investment, we will conduct research to: 1) understand the impact of social isolation on cognitive function; and 2) identify vulnerable subgroups who may benefit the most from future interventions to address social isolation and thereby improve cognitive function. Our research fits into the domain of ""social determinants of health"" because we study social factors that positively or negatively affect healthy aging. Our specific focus is on social isolation and cognitive function. Social isolation is comprised of many elements such as a lack of social networks. Cognition is also multifaceted and will be examined for overall cognitive impairment, and within specific domains critical to healthy aging (memory and executive function). The data are rich and support this extensive investigation of social isolation and cognitive function, providing key evidence for social interventions to improve the health of middle-aged and older Canadians.",2020,2023,University of Waterloo,154109.25,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C10744,174918,"How has the COVID-19 pandemic impacted the mental and physical health of Indigenous people in Canada: Taking stock of challenges, needs and factors of resilience in the context of a global crisis","The COVID-19 pandemic has deeply impacted the mental and physical health of individuals around the Globe. Significant increases in stress, anxiety and depression levels have been reported. Furthermore, it is anticipated that many chronic illnesses unrelated to COVID-19 may worsen because they are receiving lower medical attention. Concerns have been raised about disproportionate direct and indirect impacts on Indigenous health. Firstly, the cumulative pressure that this crisis is imposing on healthcare systems is likely to aggravate pre-existing difficulties faced by Indigenous peoples to access appropriate and culturally safe healthcare. Secondly, the progressive widening of socioeconomic disparities resulting from this crisis is taking a greater toll on Indigenous communities. Thirdly, fundamental specificities and strengths of Indigenous communities may influence the health-related consequences of this pandemic. Led by the Ottawa Aboriginal Coalition, in collaboration with Indigenous patient representatives and an interdisciplinary research team, this project will converge Indigenous methods nested in wholistic health approaches with patient-oriented research to investigate the direct and indirect impacts of this global crisis on the health of Indigenous peoples in Canada. This will be done in three phases via Indigenous-led : i) analyses of existing survey data collected during the first pandemic wave, ii) collection of oral/narrative evidence during virtual focus groups structured around Sharing Circles traditions, and ii) co-creation and diffusion of a survey focused on Indigenous health. Knowledge translation and advocacy activities will take place dynamically across the different project phases to enable rapid impacts.",2020,2022,University of Ottawa/Université d'Ottawa,132957,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Community engagement,2021 +C10745,174919,Defining the impact of pre-existing host immunity on SARS-CoV-2 incidence and COVID-19 clinical outcome,"Clinical outcomes are highly variable after SARS-CoV-2 infection (COVID-19), ranging from asymptomatic infection to severe disease. Very soon after exposure to viruses our innate immune responses are triggered, while the development of adaptive host T cell responses takes longer but may give long-lasting protection against reinfection. Interestingly, T cell responses against COVID can be detected in about 50% of uninfected individuals, presumably induced by prior infection with other seasonal coronaviruses. We propose to study the impact of pre-infection innate immune responsiveness and coronavirus-specific T cell responses on subsequent COVID infection rates and disease severity. A June report from Kenya found that 10% of Nairobi residents had already had COVID-19, and we hypothesize that female sex workers are at particularly high risk due to their inability to maintain social distancing. Drs Beattie (London, UK), Kimani (Nairobi, Kenya) and Kaul (Toronto, Canada) established the Maisha Fiti cohort of female sex workers in Nairobi, Kenya in 2018, to study immune pathways linking violence experience to HIV risk: 750 HIV uninfected sex worker participants were enrolled in late 2019, just before the COVID pandemic struck, with the storage of blood plasma and viable peripheral blood mononuclear cells (PBMC) for subsequent immune analysis and collection of very detailed data regarding women's experience of violence. All participants are now returning for repeat sampling and counselling; we have added a detailed survey regarding respiratory symptoms, and have received approval for SARS-CoV-19 serology. This will allow us to work with these unique pre-COVID blood samples to define the impact of pre-existing innate and COVID-specific immune parameters on subsequent SARS-CoV-2 acquisition and disease severity.",2020,2023,University of Toronto,386784,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sex workers,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe,,,,Canada,Canada | United Kingdom | Kenya,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2021 +C10746,174920,A pragmatic randomized controlled trial of a CKD specific telemonitoring platform to minimize adverse outcomes in high risk CKD patients.,"The COVID-19 pandemic has changed the way patients with chronic kidney disease (CKD) are cared for in Canada. Since CKD patients are at high risk of getting very sick from COVID19, they are being cared for with ""virtual visits"", with telephone or video conference calls. While this helps prevent spread of the virus it makes taking care of kidney problems more difficult. CKD patients need careful monitoring of kidney function, blood pressure and weight; of how they feel; and they need education about their kidney disease, diet, and choices for dialysis or kidney transplant. Simple phone or video calls is not enough for proper care.. Additional home monitoring is needed to improve virtual care for CKD patients. We developed a home monitoring kit called VIEWER which is designed for CKD patients and includes an iPad, a blood pressure monitor, a weigh scale, a finger-tip oxygen monitor, and a motion tracker (like a FitBit). All of these devices talk wirelessly (by Bluetooth) to the iPad. The VIEWER app guides patients through a daily home assessment. The app helps patients do a symptom questionnaire once a week to monitor how they are feeling. Patients can see all their information, and can text, call, or video the health team through the iPad. The health care team can see all this information to help assess changes and to guide treatments. To test if VIEWER improves care, we will do a type of study called a randomized clinical trial (RCT). We will ask 340 patient volunteers with low kidney function (<15%) to take part. Half the patient volunteers will use the VIEWER for 6 months, and half will continue with usual care in the clinic. A computer will randomly choose (like a computer coin flip) which patients are assigned to each group. We think VIEWER will reduce how often patients visit the emergency room, are admitted to hospital, or need emergency dialysis. If the trial results are positive, we will work to make VIEWER available to more people with CKD.",2020,2023,University of Manitoba,444197.25,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +C10747,174921,"Evaluation of a digital, rapid self-sampling strategy for individuals with suspected COVID-19 infection in South Africa and India","With over 35 million cases and 1 million deaths worldwide, COVID-19 is the most infectious pandemic to date. India has the second highest number of cases (over 5 million) with 80,000 deaths while South Africa has 651,521 cases and 15,641 deaths. Many individuals infected with the virus are unaware of their serostatus; they can easily transmit the virus to others unknowingly. Diagnostic solutions that can expand the capacity of the healthcare system, save healthcare worker time and resources, are urgently needed. We propose a strategy using rapid antigen tests, with easy to use, self-sampled nasal swabs and a digital application/platform to provide up-to-date, evidence-based information on the virus, guidance on performing the test and collecting the sample, and linkages to care according to health guidelines. We will test our strategy for its speed, and efficiency in triaging populations to care or prevention in 550 patients in both Manipal, India and in Cape Town, South Africa (1100 participants total), and compare it to the conventional COVID-19 testing strategy in 1100 participants. This innovative, digital strategy will be open access and will impact pandemic control globally. The strategy will help people to know their COVID-19 status, detect new infections, and decrease the burden on the overwhelmed healthcare system.",2020,2022,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,299153.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C10748,174922,Social polarization and behavioral intentions during the COVID-19 pandemic: A multi-site study of risk and protective factors in Canadian youth,"The COVID-19 pandemic accentuates social inequalities and exacerbates social polarization, fueling support for diverse forms of violent radicalization, including hate speech and crime. In turn, social polarization promotes reservation and opposition towards public health best practices and guidelines related to COVID-19, including social distancing, wearing masks, and receptiveness to future vaccines. There is an urgent need to bridge expertise in the fields of social polarization, violent radicalization and COVID-19 to inform preventive action at the local and national level that reduces violence and increases behavioral intentions to engage in COVID-19 prevention efforts during the present health emergency. A socio-ecological framework that emphasizes the importance of multiple levels of risk and protective factors is needed to understand and respond to these public health issues, Research aims include: 1) Identify risk and protective factors associated with attitudes towards violent radicalization and COVID-19 behavioral intentions among Canadian young adults, and 2) Explore city and provincial-level variations related to these social phenomena. College and university students in nine cities in three provinces (Quebec, Ontario and Alberta) will participate in an online survey on social polarization, violent radicalization and COVID-19 in 2021. Results will inform public health communication strategies to promote engagement in public health measures such as uptake of a vaccine and decrease support for violent radicalization. In addition, results will be used to design and implement intervention programs in the education and health sectors that respond to local and regional socio-cultural dynamics related to violent radicalization and COVID-19, informing institutional and policy decision makers during and in the aftermath of the pandemic.",2020,2022,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,190370.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2021 +C10749,174923,Provision of services for trauma- and stressor-related (TSR) disorders during a pandemic: Investigating the Utility of Reconsolidation Therapy Delivered Online,"The COVID-19 pandemic has induced a variety of trauma- and stressor-related (TSR) disorders in the population, according to a large international online survey conducted by our research team in May 2020. There currently exists a knowledge gap in our capacity to diagnose and treat these common mental disorders in confinement settings (e.g., via tele-heath). We aim to build capacity by (1) training providers to deliver an evidence-based treatment (Reconsolidation Therapy) using an on-line delivery format and (2) pilot-testing Reconsolidation Therapy, an evidence-based treatment developed by our team to treat TSR disorders, and (3) disseminate widely this knowledge via project partner, the Canadian Psychological Association. We will be using both quantitative (statistics) and qualitative (narratives generated by group interviews) methods to adapt current diagnostic assessments to an online format, as well as evaluate the treatment ease of delivery and (preliminary) efficacy. Considering the uncertainty of the COVID-19 pandemic and its duration, our project will contribute to the development of secure, accessible, and evidence-based online treatments for STRD that meets the needs of patients and treatment providers in Canada and beyond.",2020,2022,CIUSSS de l'Ouest de l'Ile de Montréal Douglas Hospital,190370.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Health Systems Research,Health service delivery | Health workforce,2021 +C10750,174924,Deciphering the immunopeptidomic landscape of COVID-19 disease,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Between December 2019 and September 2020, SARS-CoV-2 had infected more than 30M people and killed more than 1M. Ease of transmission combined with disease severity have led leaders around the world to restrict individual movements and promote physical distancing measures to limit the spread. Therefore, rapid delivery of safe and efficient vaccines against SARS-CoV-2 is the top priority. Importantly, the development of efficient vaccines can be accelerated by a clear understanding of the SARS-CoV-2 targets that are recognized by the human immune system. Until now, very limited information is available about those targets. In addition, SARS-CoV-2 is mutating as the pandemic persists, but it is unclear how those mutations influence the ability of the immune system to eliminate the virus. Here, we propose to deploy an innovative viral epitope discovery platform to identify those mutated and non-mutated targets in a rapid, systematic and unbiased manner. The proposed research will therefore assist vaccine design and will facilitate the evaluation of vaccine candidates as they advance in the clinic.",2020,2024,Centre hospitalier universitaire Sainte,583020,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C10751,174925,SARS-CoV-2 genotype-dependent pathogenesis and transmission,"As the SARS-CoV-2 virus circulates in the Canadian population, it is important to monitor if and how the virus changes. To do this, there is a new national consortium called the Canadian COVID-19 Genomics (CanCOGeN) network to determine the genetic code of the viruses infecting Canadians. Most changes in viral sequence will serve as markers but won't affect the virulence or transmission of the virus. However, some mutations will change how the virus causes disease, transmits or responds to antivirals and vaccines. We have isolated the SARS-CoV-2 virus in the high containment laboratory at the University of Toronto. We would continue to work on viruses from patients to rapidly determine whether there are differences in disease severity and transmission if the virus itself changed, particularly if this affects response to vaccines and antivirals. We will establish small mammal infection and transmission models for SARS-CoV-2 to answer critical questions as they relate to viral disease and spread. We are also building a repository of viruses to support other researchers and innovators in Canada. This work will directly impact individual patient care and public health as the pandemic unfolds with unmitigated person-to-person transmission in the absence of medical counter measures such as vaccines and therapeutics, and remains important as these are put into broad use to ensure that these methods remain safe and effective.",2020,2024,Sunnybrook Research Institute,484084.35,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2021 +C10752,174964,The impact of the COVID-19 pandemic on substance use problems and services: Knowledge synthesis with Indigenous Nations and organizations,"The COVID-19 pandemic has had a serious impact on Indigenous Peoples across Canada. One area of concern pertains to the exacerbation of substance use problems and the disruption of substance use services for Indigenous youth. This study seeks to understand the impact of the pandemic on substance use risk and resilience among Indigenous youth, via a knowledge synthesis including (a) a rapid review of academic research and other available materials (such as news articles and reports) and (b) interviews and Talking Circles with Indigenous communities and service providers in eastern Canada. The study conception stems from the Indigenous Working Group (IWG) of the Quebec-Atlantic Node of the Canadian Research Initiative in Substance Misuse. The project is a partnership with two First Nations communities, an Indigenous SU treatment facility, and other partners from Quebec and Atlantic Canada. Qualitative interviews and Talking Circles (via video-conferencing technology, as necessary) with key stakeholders, clinicians, and youth will be conducted in order to understand key needs, challenges, and strengths of Indigenous youth in response to the pandemic. The project will include seeking to understand the pandemic's impact on access to culturally-safe services, including access to Indigenous traditional healing practices. The study will be guided by a Two-Eyed Seeing framework, which seeks to understand both Indigenous and Western biomedical perspectives. All research will be conducted in consultation with an Indigenous research advisory council. Data will be analyzed using principles of thematic content analysis. Knowledge from this study will be disseminated to Indigenous Nations and organizations across Canada, as well as to federal and provincial agencies.",2020,2022,McGill University/Université McGill,79000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Minority communities unspecified,Health Personnel | Physicians,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Other secondary impacts | Health service delivery,2021 +C10753,174965,Kloshe Tillicum: Creating trustworthy and culturally meaningful public health guidance to address COVID-19 in Indigenous communities,"Trust between public health authorities and the public is required to successfully reduce the impacts of COVID-19 and to slow the epidemic. Participation in contact tracing activities, compliance with physical distancing measures, and uptake of vaccines all depend on this trust. The COVID-19 pandemic has unfortunately revealed a concerning trend, with a gap in trust between many Indigenous communities and public health authorities. Kloshe Tillicum means ""good relations"" in Chinook Jargon. The rapid research we propose builds on longstanding relations between our team-the BC Centre for Disease Control (BCCDC)'s Chee Mamuk program-and numerous Indigenous communities through BC, as well as a provincial survey examining misinformation related to COVID-19 (N=3,073 respondents, April 2020). In conversation with First Nations partners of Chee Mamuk, we have heard members of some communities express confusion over discrepancies in COVID-19-related messages they receive from different levels of government and different sources (media, social media, word-of-mouth, public health, etc.). Meanwhile, other communities have told of missed opportunities for meaningful Indigenous community involvement in public health-directed contact tracing efforts. This rapid knowledge synthesis, working with Indigenous communities throughout BC and the BCCDC, will assess community-led strategies to build trust with regard to the following COVID-19 related activities: testing, contact tracing, social/physical distancing, and vaccination. We will meet this objective through Indigenous and community-led methodologies that have been established and used by our team for many years. Through activities-based focus groups, we will identify culturally meaningful ways to engage communities in COVID-19 prevention measures.",2020,2022,Simon Fraser University,76386.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2021 +C10754,174966,Enhancing culturally-safe ways for community wholistic health and wellness aspirations during COVID-19.,"The COVID-19 pandemic has significantly impacted Indigenous communities throughout Canada. Current COVID-19 restrictions have affected the ability for Indigenous peoples to engage in traditional community activities and gatherings. As a result, wholistic components of community health and wellness (spiritual, emotional, mental, and physical wellness) have been negatively affected. Therefore, this community-based research aims to create a novel and virtual community-driven health and wellness program for urban and rural Indigenous communities within British Columbia. This Indigenous-led and community-based program will reflect the strengths and aspiration of the Indigenous communities. Furthermore, community-based participatory research methodologies will be used to increase empowerment and the self-determination of Indigenous peoples within BC. The findings will be shared with community participants, leaders, and available online as in accordance with the OCAP Principles. The community feedback gained in the evaluation of the community-based program will be used as a guide to develop an online community-based health and wellness toolkit. The toolkit will outline best practices and strategies by outlining culturally safe ways to promote community health and wellness in response to COVID-19. It is anticipated that a virtual community-based traditional health and wellness program and toolkit can be used as a guide to enhance ties to wholistic health and wellness within Indigenous communities throughout Canada.",2020,2022,University of British Columbia,78465.96,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Social impacts,2021 +C10755,174967,How Indigenous communities in Quebec responded to COVID-19: A synthesis of community-level asset mobilization during the first wave of the pandemic,"With the arrival of COVID-19 Indigenous communities in Quebec moved quickly to protect the health and wellbeing of their people. Individuals, community organizations, informal and non-health institutions have initiated numerous activities with the intention of protecting people from infection and mitigating the unintended impacts of public health measures on other health determinants. At writing, the incidence of C-19 in the First Nations and Inuit communities in roughly 20 times less than that of the province at large. Community mobilisation is an important yet understudied aspect of this remarkable success. This knowledge synthesis and translation project builds on preliminary work documenting the mobilization of community-level assets in defence of health. Using social media and other web sources, we have catalogued instances of community asset mobilization by the 55 indigenous communities in the province between March 1 and July 31, 2020. A geo-referenced archive of all instances - over 1500 at present - is nearing completion. The aim of our proposed knowledge synthesis project is to engage representatives of each of the 10 First Nations and the Inuit communities of Quebec in a collaborative analysis of the data gathered. The analysis will focus on creating Knowledge Translation products and processes that can integrate into future epidemic and disaster planning efforts. This project will broaden the understanding of Indigenous community-level response to pandemic disease threat in several ways and contribute to: 1) optimizing disease containment strategies, 2) facilitating effective public health interventions, 3) recognizing and valuing citizen engagement, 4) deepening the understanding of community resilience and 5) mitigating the unintended effects of the COVID-19 response on other determinants of health.",2020,2022,Université Laval,78355.36,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2021 +C10756,174968,An Environmental Scan of Service Adaptations in Community-Based Harm Reduction Services for Indigenous Peoples in Response to the COVID-19 Pandemic,"INTRODUCTION: The Canadian Aboriginal AIDS Network (CAAN) and the Dr. Peter AIDS Foundation (DPAF) are partnering to propose a real-time, knowledge synthesis environmental scan of Indigenous and non-Indigenous harm reduction organizations across Canada to identify: 1) How harm reduction programming for Indigenous people has been impacted by the COVID-19 pandemic, 2) how such programs have adapted in response to the pandemic, and 3) what knowledge translation resources could help address gaps in services resulting from the COVID-19 impact on harm reduction programming. This scan will result in the co-creation of wise practices for culturally responsive Indigenous harm reduction services which will support harm reduction organizations in sustaining and improving the ways that they deliver harm reduction services to their Indigenous clients. METHODS: The methodology of this environmental scan is guided by several core foundations of Indigenous Ways of Knowing and Doing, OCAP, Two-Eyed Seeing, and Ermine's 'ethical space of engagement.' This environmental scan - using a strengths-based, trauma-informed, culturally responsive, and asset-mapping approach - will include published and grey literature, as well as sharing circles and interviews with key informants representing harm reduction organizations. The research team of experts in harm reduction, knowledge translation, and Indigenous epistemologies will ensure that this project proceeds from an Indigenous research epistemology in accordance with CIHR's definition of Indigenous Health Research and Meaningful and Culturally Safe Health Research. OUTCOMES: This project will create an evidence base of culturally safe harm reduction programming for Indigenous Peoples in the context of COVID-19. We will subsequently use this evidence to develop a suite of capacity-building resources for harm reduction programs and services that are grounded in Indigenous Knowledges for diverse community contexts.",2020,2022,Canadian Aboriginal AIDS Network,79000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C10757,174969,Developing wise practices for a culturally safe rapid public health response to COVID-19 with Pikwàkanagàn First Nation,"The aim of this research is to understand how the Algonquins of Pikwakanagan ways of knowing can inform public health responses at local, provincial, federal and global levels, to mitigate the negative impacts of COVID-19 and maximize the health of Indigenous Peoples. At the time of writing this proposal, Pikwakanagan First Nation had no confirmed cases of COVID-19 despite high prevalence of people at risk. Our team includes an Algonquin First Nations Knowledge Keeper of traditional ways of knowing and practices, a health and social services supervisor within Pikwakanagan First Nation, and an Indigenous scholar from the First Nation with expertise in public health policy and sex and gender. We are using innovative methods to identify wise practices and inform culturally safe policies, programs, infrastructures and responses that include: sharing circles, journey mapping, photography and Anishinaabe symbol-based reflection, individual interviews and consultations. To facilitate a rapid response and impact, our knowledge translation plan involves the use of short video as part of a documentary film to rapidly create and share learnings and practices with a broad and diverse audience, in addition to disseminating summaries to Indigenous health forums, provincial and national health agencies and ministries. Deliverables can inform Indigenous and non-Indigenous governments and community members re-evaluate their own disaster mitigation approaches in pandemics or for future threats.",2020,2022,University of Ottawa/Université d'Ottawa,158000,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2021 +C10758,174970,"CO-Away: Evaluation of a digital platform for Indigenous self-governance, determination, and data sovereignty","With the 2nd wave of COVID-19, cases are currently rising across northern Indigenous communities, with the active caseload more than doubling in northern Saskatchewan reserves in mid-November 2020. More critical to this project, an Elder and youth member of our Advisory Council recently tested positive, reiterating the dire need for scalable, innovative platforms such as CO-Away to minimize the impact of subsequent COVID-19 waves in Indigenous communities in Saskatchewan. CO-Away is a culturally appropriate digital epidemiological platform to monitor, mitigate, and manage Coronavirus disease (COVID-19) outbreaks. The CO-Away platform consists of two key components - a frontend virtual care smartphone application (app), and a backend digital decision-making dashboard. The app provides three key precision medicine services that are specific to each citizen: 1) continuous risk assessment of contracting COVID-19 via the virtual doctor feature; 2) evidence-based public health communication; and 3) Citizen reporting of food availability, access to public services, and COVID-19 symptoms and test results - these culturally-responsive features have been co-created with Ile-a-la-Crosse Metis decision-makers based on imminent community needs and preferences. The data from the virtual care app is transferred in real-time to a digital decision-maker dashboard, which is securely accessed by the Metis Mayor of Ile-a-la-Crosse. The dashboard will enable the Mayor's office to assess both individual and community risk, including direct risk of COVID-19, as well as indirect effects such as food insecurity. The primary purpose of this three-year project is to evaluate the implementation of CO-Away for COVID-19 rapid response, while readying the CO-Away digital infrastructure for other existing and emerging health crises in Indigenous communities.",2020,2022,University of Regina,158000,Human Populations | Not applicable,Unspecified,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Approaches to public health interventions | Communication | Other secondary impacts,2021 +C10759,174971,"Impacts of COVID-19 on Virtual Elder-led Supports for Survivors of Violence: Participatory Approaches to Response, Evaluation, and Recovery","Little has been documented about the impacts, adaptation, resiliency, leadership, and effectiveness of Indigenous-led virtual support programs that have arisen during the COVID-19 pandemic. Immediate research is needed to evaluate the impacts COVID-19 has had on the development and delivery of virtual Elder-led supports for Elders, Grandmothers, knowledge keepers, and Indigenous survivors of violence, particularly as COVID-19 countermeasures have exacerbated pre-existing health and social inequities, deepened social isolation, and restricted Indigenous ceremonies (UN, 2020). Our community-based, Indigenous-led research team proposes the upscaling, delivery, and evaluation of the ""Virtual Resilience & Wellness Journey Program Pathway"" at the Native Women's Association of Canada (NWAC)'s Resiliency Lodge, an Elder-led program that provides distinctions-based, land-based, culturally-safe, trauma-informed support online for Indigenous women, two-spirit, and gender-diverse people healing from trauma and violence. We propose the use of participatory action methodologies with Elders, Grandmothers, Knowledge Holders, Resiliency Lodge staff, and other Indigenous-led virtual support programs in Canada to address the research questions: What are the impacts of COVID-19 on the development and delivery of Elder-led support services? How are these Elder-led support services adapting to the impacts of COVID-19? How can we engage Elders and other Knowledge keepers in the development of culturally and contextually relevant evaluation framework to evaluate best practices for virtual Indigenous-led support? Our research approach ensures research findings address critical gaps in knowledge of culturally safe COVID-19 prevention, preparedness, response and recovery strategies, accelerates community-led knowledge, and strengthens Elder-led program infrastructure for communities on the frontlines of culturally safe violence prevention and intervention.",2020,2022,Native Women's Association of Canada,157976.3,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Indigenous People | Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2021 +C10760,174972,"Evaluating COVID-19 Mental Health and Child Welfare Supports at the Under One Sky Friendship Centre in Fredericton, New Brunswick","The COVID-19 pandemic, and its associated economic, social and political consequences, have had a noticeable and detrimental impact on urban Indigenous communities. Separation from their families and communities, job loss, and limited social and educational opportunities are adding to the sense of isolation many urban Indigenous peoples already feel. In response, the Under One Sky Friendship Centre in Fredericton, New Brunswick has been able to quickly develop and launch the Sakelemelsowaken Family Success Program, which consists of two pilot wellness initiatives to address the unmet and exacerbated needs of the regional Indigenous community: one is an Indigenous nursing outreach program to support the strengths and enhance the success of Indigenous families; the other, an Indigenous mental wellness counselling and referral program that serves everyone who seeks support. This research project will entail a community-driven evaluation of this COVID-19 related wellness program. The evaluation will help identify and assess priority goals and outcomes, from the point of view of the Friendship Centre, its clients, Elders and other stakeholders. This will inform adjustments in services in order to best meet the needs of Fredericton's Indigenous community; improve our understanding of the immediate impacts of COVID-19 on urban Indigenous populations, including any differences in impacts faced by men, women, children and gender diverse individuals; and provide much needed evaluation and improvement data for wellness services of this nature, which are common across Canada. Finally, it will build capacity within the Friendship Centre to better collect data and evaluate their own programming going forward.",2020,2022,University of New Brunswick,157929.69,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Policies for public health, disease control & community resilience",Social impacts | Health service delivery | Community engagement,2021 +C10761,174973,Proof of concept of wastewater-based surveillance for SARS-COV2 to mitigate secondary COVID-19 disease transmission in First Nations in Alberta,"We propose to track SARS-COV2 in the wastewater (WW) in targeted First Nations in Treaty 7 in Central/Southern Alberta. SARS-COV2 genetic material is excreted in the poop from infected individuals, often before symptoms start. Our research team has developed and deployed methods within an urban setting with centralized sewage for WW processing and for quantifying the amount of this signal. We will leverage this information to build a surveillance program with partnered First Nations to translate and mobilize monitoring into rapid community responses, enabling community-based targeted screening, isolation of households/groups and supportive distancing- thereby mitigating secondary spread. We will accomplish the following; 1. Develop procedures for efficiently collecting and transporting WW samples from communities to a central laboratory. 2. Within 48 hours multiple SARS-COV2 RNA markers and controls will be quantitatively processed to assess COVID-19 trends. 3. Develop a collaborative model in which real-time data is shared between public health experts and community leaders. 4. Develop health and technical tools to help contain secondary infections (ie, community spread) once a potential cluster has been identified, including preparing Knowledge Keepers and primary care teams with technical knowledge, and linking understanding of community vulnerability based on access to basic infrastructure. Our trans-disciplinary team brings together Indigenous leaders, Alberta Health Services, and University subject matter experts from the Faculties of Science, Engineering and Medicine. Co-leads include scholars who work in close partnership with First Nations on health and infrastructure-related initiatives that intersect with COVID-19 responses. Together, we have extensive experience with OCAP™ principles-aligned research and funding in partnership with First Nations, and are therefore in a position to engage eligible Nations to partner on this initiative.",2020,2022,University of Calgary,158000,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2021 +C10762,174974,Enhancing Indigenous Health as a result of the COVID-19 Pandemic: Developing Indigenous Patient Experience Indicators of High Quality Virtual Primary Care,"In response to the COVID-19 pandemic, rapid shifts in the delivery of primary health care (PHC) services to virtual care models occurred in Canada. Insufficient access to primary care may undermine both the capacity to prevent transmission of COVID-19 infection, as well as effectively manage pre-existing chronic diseases. Moreover, relational factors necessary to provide high quality PHC may be inhibited by virtual care provision. This research aims to develop and test a tool measuring 'patient experiences of care' that is oriented to monitoring and improving the quality of virtual primary care contacts with Indigenous patients. Mixed-methods will be used to a) generate qualitative data; b) develop and pilot a tool; and c) refine the tool after piloting. Semi-structured interviews with Indigenous individuals accessing virtual PHC and their care providers will be completed to elicit and develop key indicators of healthcare quality. Data generated will be integrated with Indigenous primary care quality of care frameworks and other health care quality tools to generate a new tool specific to virtual care provision. Patient, provider, and systems lead perspectives will be analyzed using Framework Analysis to highlight experiences and understandings of chronic disease management for Indigenous populations during COVID-19. Survey development will integrate findings from interviews and published health service utilization data with existing Indigenous primary care health access models and health quality frameworks to generate a survey tool. The developed tool will be piloted with approximately 20-30 Indigenous patients accessing providers through virtual care and approximately 15-20 health care providers. This work will facilitate the improvement of virtual primary care provision for Indigenous patients arising from COVID-19 by developing a robust patient experience measure based on indicators of Indigenous health, grounded in patient and provider experiences.",2020,2022,University of Calgary,157463.59,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery,2021 +C10763,174975,"kitatipithitamak mithwayawin: Evaluating impacts of an existing Indigenous-led project on COVID-19, which includes past work on risk communication, present work on digital health, and a future international gathering for impacted Indigenous communities around the world.","COVID-19 has swept around the globe and has already resulted in over 1.5 million deaths. In the past, Indigenous people were devastated by pandemics including smallpox, Spanish flu and H1N1 and cases of COVID-19 are now rising quickly in many communities. This proposal builds on the activities of our existing project that focuses on COVID-19 and Indigenous people. Named kitatipithitamak mithwayawin, Cree for control or sovereignty over wellbeing, its goal is to document the past, present and future impacts of pandemics. And to support Indigenous communities as they respond to COVID-19. This proposal similarly aims to extend its scope and impact in three ways. i)Past work: Evaluate impacts of our existing activities focusing on Indigenous risk communication. These reflect videos, webinars, workshops, and infographics that are shared on our project website < http://covid19indigenous.ca/> and Facebook page < https://www.facebook.com/covid19indigenous/> ii)Present work: Expand a new digital health initiative that will use web and mobile apps to provide health directors with real-time health data for local decision-making. We will expand these efforts to include any First Nations, Metis, and Inuit communities in Canada wanting to participate. We will also evaluate the benefits and any shortcomings of these apps in local decision-making regarding COVID-19 and wellbeing as a whole. iii)Future work: Hold an international (virtual) conference in May 2021 that brings Indigenous communities and scholars from around the world to share their experiences with COVID-19 and to learn from one another. This will ideally result in an Indigenous-led network of support that helps communities respond to pandemics in the future. The impacts of the conference and network will also be evaluated. In closing, this proposal expands our existing Indigenous-led project on COVID-19 and does so in ways that serve the interests of any and all Indigenous communities regardless of location.",2020,2022,University of Manitoba,158000,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2021 +C10764,174976,"Towards Culturally Safe and Equitable Sexual, Reproductive Health and Justice for Indigenous cis and trans Women and 2SLGBTQ+ peoples in the context of COVID-19: Amplifying the Voices of gender diverse Indigenous women","Equitable access to culturally safe sexual health, reproductive care and justice for Indigenous women, girls and 2S/LGBTQ+ peoples is an issue of concern across Canada. COVID-19 measures and context has amplified existing inequities and barriers to care that already existed for many Indigenous peoples, particularly marginalized groups. This study aims to examine the impact that COVID-19 on shaping access and utilization of sexual and reproductive care and amplify Indigenous voices using community-based participatory and Indigenous grounded research methods. Data will be drawn from 2 established prospective cohort studies to examine the impact of COVID-19 on Indigenous peoples in Metro Vancouver with analysis guided by expert groups of Indigenous elders and community members. Arts-based and Indigenous methodologies will be used to gather Indigenous community voices and create recommendations for enhancing equitable and culturally-safe access to sexual, reproductive care and justice in the ongoing context of COVID-19.",2020,2022,Centre for Gender and Sexual Health Equity,157334.82,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Health Systems Research | Secondary impacts of disease, response & control measures",Health service delivery | Social impacts,2021 +C10765,175622,Coronavirus Variants Rapid Response Network: CoVaRR-Net,"Canadians are concerned about how mutations in SARS-CoV-2, the virus that causes COVID-19, will impact how the virus is transmitted, whether it makes people more sick, and whether immunity conferred through previous exposures to SARS-CoV-2 or vaccination will still be able to fight off a mutated virus. Mutations to SARS-CoV-2 that have these outcomes are called ""Variants of Concern"" (VOC). CoVaRR-Net, a rapid-response Network, will assist in the Government of Canada's overall strategy to address the threat of emerging VOC. The Network will enable the mobilization of Canadian research assets to answer critical and immediate questions regarding threats, such as increased transmissibility, pathogenicity and vaccine resistance, posed by an emerging VOC. CoVaRR-Net will act as Canada's integrated platform for determining how VOCs impact Canadians from diverse communities and demographics. We will work collaboratively with national and international bodies such as the National Microbiology Lab, provincial/territorial public health labs, and the Canadian COVID-19 Genomics Network that are tracking how SARS-CoV-2 is mutating in real time. Central to CoVaRR-Net's service work will be a newly created Biobank for rapid sharing of samples and data with other biobanks across Canada in order to have a harmonized approach to the war on COVID-19. Built on a foundation of eight thematic areas (Immunology & Vaccine Protection, in vitro & in vivo Characterizations, Functional Genomics & Structure Function of VOCs, Viral Genomics & Sequencing, and In Silico Modelling & Computational Biology, Public Health, Health Systems & Social Policy Impacts, Indigenous Outreach and Knowledge Mobilization), CoVaRR-Net is poised to contribute to the Canadian effort to mitigate the impact of harmful VOCs on citizens of Canada and on the world population.",2021,2021,University of Ottawa/Université d'Ottawa,7110000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Immunity | Disease surveillance & mapping",2021 +C11361,872539,Pan-genome Graph Algorithms and Data Integration,"Researchers involved in PANGAIA are investigating how massive amounts of genome sequence data can be ordered and analysed for their use in biomedicine. Their work has important implications in areas such as bacteria and virus research, investigation of drug resistance mechanisms and vaccine development: big data technology can help to identify the characteristics of new strains of viruses such as SARS-CoV-2 and bacteria by comparing their genomes.",2020,2023,UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA,1235884.18,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Italy,Italy,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C11368,"170352, 175506",Development and implementation of rapid metagenomic sequencing coupled with isothermal amplification point of care testing for viral diagnostics [Added supplement: COVID-19 Variant Supplement],"Infectious pandemics or plagues have altered human history since the beginning of time. Today we face the threat of viral pandemics spreading through human populations disseminated fueled by the ease of international travel which has become commonplace. SARS, influenza, and now the 2109 novel coronavirus are examples of just a few of these pandemics. We must create novel tools that enable us to rapidly identify the virus and then develop a test that can reliably test for the virus in patients. The test has to be portable and taken to the bedside where patients are quarantined so that these individuals do not further transmit viruses in our hospitals and public places.",2020,2022,University of Calgary,748198,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C11369,"170364, 175516, 175567","Understanding the pathogenesis of COVID-19 [Added supplements: COVID-19 Variant Supplement, COVID-19 Variant Network]","Pulmonary infections by viruses such virulent Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) and Middle East Respiratory Syndrome (MeRS) CoV associated with significant morbidity and mortality. Clinically, infections by these viruses are associated with a pronounced lung inflammation, causing respiratory problems that often develop in secondary pneumonia. Inflammation is the result of immune activation in response to infection. When activation is too pronounced or sustained for extended periods of time, complications occur. Two main mediators of inflammation are known: Cytokines and lipid mediators of inflammation (LMI). In the current proposal we will study the inflammatory response during infection/exposure of lung and blood cells to the newly described COVID-19 and compare this response to that of SARS-CoV-2 and MeRS-CoV to obtain correlates of pathogenicity between these viruses. We will use primary lung cells and white blood cells from donors to conduct our studies. The mediators of inflammation will be identified and quantitated using state of the art methodology available in our laboratories. More than 200 LMI and 150 cytokine/cytokine receptors will be examined. Upon completion of this proposal, a detailed analysis of the response of primary epithelial cells and leukocytes to COVID-19 will be obtained, enabling the rational design of therapeutic strategies to help combat COVID-19.",2020,2022,"CHU de Québec - Québec, Québec",409246,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2020 +C11370,"172660, 175519",Protecting healthcare workers from COVID-19: A comparative contextualized analysis [Added supplement: COVID-19 Variant Supplement],"This research focuses on measures to protect healthcare workers (HCWs) who are at substantially increased risk because of their direct contact with COVID-19 infected patients - and with considerable variation being experienced internationally in different settings. Although there is general agreement on many aspects of policy to protect HCWs, approaches have varied widely with very limited availability of contextualized evidence to guide local decisions. Often differences have been due to availability of specific personal protective equipment (PPE-e.g. N95 respirators, masks, gloves, gowns); sometimes differences have been due to operational necessities (e.g. whether exposed HCWs can continue to work while wearing PPE); sometimes variations in policies relate to availability of COVID-19 test kits or related reagents (e.g. criteria for testing or whether pre-return-to-work testing is implemented); approaches to exposure monitoring and contact tracing for HCWs also vary widely. It is critically important for policymakers to understand consequences of these variations, as well as scrutinize their scientific and contextual rationales. This proposal asks ""What works to protect HCWs, in what contexts, using what mechanism, to achieve what outcome?"" By building on a strong track record of interdisciplinary research in exactly this field, with well-established international networks with expertise in infection control and occupational health, and a long-history of relationship-building to facilitate this research, this team is extremely well-positioned to conduct this highly relevant research and provide world leadership in this area. It will be conducted through in-depth case studies conducted in Vancouver, Canada and Gauteng, South Africa as well an international cross-country comparative analysis based on surveys and experiences in protecting healthcare workers and a case-control study of workers with COVID-19 infection versus other workers in their same facilities.",2020,2021,"University of British Columbia - Vancouver, British Columbia",341448.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,IPC in health care settings,2020 +C11371,"172731, 175529",Improving Outcomes in Individuals with COVID-19 with Renin-Angiotensin System Inhibition: The COVID-RASi Trial [Added supplement: COVID-19 Variant Supplement],"Cardiovascular disease is not only the #1 killer chronically, but is also the #1 killer in COVID-19. Elderly patients with previous heart attack or stroke, or hypertension or diabetes, have high risk of getting infected. Surprisingly they also suffer 3 to 5 times the chance of dying compared to other infected patients. A clue may lie in a group of commonly used medicines, called renin-angiotensin system (RAS) inhibitors, including ACE inhibitors and angiotensin receptor blocks or ARBs, usually extremely protective for our cardiovascular patients. But they have come under attack because they are suspected to increase the levels of ACE2 in the body, also part of RAS, which is the receptor for the virus, or the doorway for virus to enter our body. So are these agents safe or dangerous? This has become a major source of fear for both patients and physicians alike, and a raging controversy. To answer this question, we analyzed data from Wuhan, and found that these agents actually to be extremely protective. This finding was also replicated in another study examining patients in Europe and America. However, these data looked backwards at events past, which can be fraught with hidden biases. Therefore, the world desperately needs a proper forward-looking trial to evaluate these agents in COVID-19. Together with our Canadian and international partners experienced in COVID-19 research, we are starting this large trial to evaluate whether adding ACE inhibitors, or ARB's, compared to no added treatment in high risk COVID-19 patients, can decrease the chance of dying, requiring ventilators or ICU. A positive trial showing benefit will potentially save many lives in the world, using a very simple and cheap set of medications. Even if we found the medications to be safe, it will be very reassuring for millions of patients. We want to answer this question with urgency to benefit Canadians and cardiovascular patients worldwide in this COVID-19 era.",2020,2022,"Ottawa Heart Institute Research Corporation - Ottawa, Ontario",905049.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C11496,unknown,"Health extension workers role, and information requirements during the COVID-19 outbreak in Ethiopia",,2020,-99,University of Gondar,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Ethiopia,Ethiopia,Health Systems Research,Health workforce, +C11497,unknown,Barriers faced by homeless women in accessing services in the wake of COVID-19,,2020,-99,George Institute for Global Health,,Human Populations,Unspecified,Unspecified,Unspecified,Women | Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,South-East Asia,South-East Asia,,,,India,India,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C11498,unknown,COVID-19 presentation and complications in a typical African setting,,2020,-99,Ministry of Health and Sanitation,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Sierra Leone,Sierra Leone,Clinical characterisation and management,Disease pathogenesis, +C11499,unknown,COVID 19: Screening and tracing methods in the Zambian context,,2020,-99,The Centre for Infectious Disease Research in Zambia,,Unspecified,Black,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Zambia,Zambia,Epidemiological studies,Disease surveillance & mapping, +C11500,unknown,Assessing the response to the COVID-19 pandemic in Internally Displaced Persons Camp,,2020,-99,Slum and Rural Health Initiative,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Secondary impacts of disease, response & control measures",Social impacts, +C11501,unknown,Knowledge and Preventive Practices towards COVID-19,,2020,-99,Walter Sisulu University,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement, +C11502,unknown,The Impact of the COVID-19 Pandemic on Tuberculosis Service Delivery,,2020,-99,Birat Nepal Medical Trust,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,South-East Asia,South-East Asia,,,,Nepal,Nepal,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C11503,unknown,Informational and structural barriers to uptake of preventive behaviours among Healthcare workers during COVID 19,,2020,-99,Centre for infectious disease research in Zambia,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Zambia,Zambia,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C11504,unknown,Effect of COVID-19 total lock down on severity of non-communicable diseases in HIV positive patients in Kampala,,2020,-99,World Health Organization,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,International,Africa,,,,International,Uganda,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C11505,unknown,Understanding COVID-19 survivor experiences,,2020,-99,Makerere University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Community engagement, +C11506,unknown,The impact of household structure on the effectiveness of shielding vulnerable populations against COVID-19,,2020,-99,University of Cape Town,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C11507,unknown,Perceptions and Behaviors related to Hand Hygiene for the Prevention of COVID-19 transmission,,2020,-99,Busitema University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C11508,unknown,Evaluating the public health response for COVID-19 in Sudan 2020,,2020,-99,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,,Africa,,,,,Sudan,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions, +C11509,unknown,Optimizing the World Health Organization guidelines for health care workers' protection from COVID-19,,2020,-99,Catholic University of Health and Allied Sciences - Bugando Medical Center,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Tanzania,Tanzania,Infection prevention and control,IPC in health care settings, +C11510,unknown,Implications of the cluster-containment strategy for COVID-19 control on snakebite care in India,,2020,-99,The George Insitute for Global Health,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,South-East Asia,South-East Asia,,,,India,India,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts, +C11511,unknown,Implementing behavioral adaptation to curtail transmission and mental health impact of COVID-19,,2020,-99,University of Gondar,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Ethiopia,Ethiopia,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C11512,unknown,"Risk Communication and Community Engagement Strategies, Surveillance Systems and Laboratory Testing Capacity for COVID-19",,2020,-99,Global Health Focus,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | Royal Society of Tropical Medicine and Hygiene (RSTMH),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Communication, +C12110,54121.1 IP-LS,alphaRep-HR2 entry inhibitors and a non-antigenic test for the treatment and diagnosis of COVID-19,"The SARS-CoV2 pandemic is a major health, economic and societal issue worldwide. Despite the advent of vaccines, novel therapeutic and diagnostic options are needed. Here, we wish to use S artificial nanoligands to develop novel potent entry inhibitors and a non-antigenic test for massive screening.",2021,2022,N/A,377284.78,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,,Europe,,,,,Switzerland,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2021 +C12111,52533.1 IP-LS,"Preclinical Development of the Live, Single-Cycle, Next-Generation SARS-CoV-2 Vaccine (RVX-13)","RocketVax AG, a startup company from Basel, together with academic partners in Switzerland, will develop a next-generation vaccine against SARS-CoV-2. Based on a live, single-cycle virus, this vaccine will provide a broader and more durable protection, offering a superior and long-term solution.",2021,2021,N/A,1331387.03,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,,Europe,Innovation,,,,Switzerland,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C12112,52910.1 IP-LS,Development of a novel delivery system for mRNA COVID-19 vaccines,"mRNA vaccines have showcased their tremendous potential amidst the COVID-19 pandemic. In this project, we aim to maximize the potential of mRNA vaccines by developing a novel vaccine carrier system to improve their efficacy, stability, safety, and cost-effectiveness.",2021,2023,N/A,825923.46,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,,Europe,Innovation,,,,Switzerland,"Vaccines research, development and implementation",Vaccine design and administration,2021 +C12113,52441.1 IP-LS,COVID-19 Dashboard: Early warning system for undetected SARS-CoV-2 infection and disease progression to severe COVID-19,The false-negative rate of SARS-CoV-2 testing is up to 38%. Virus transmission occurs among hospitalized patients and medical staff. Predictive models are developed including biomarkers and high-resolution data from biosignals to provide a more accurate diagnosis and live prognosis of COVID-19.,2021,2022,N/A,412556.9,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,,Europe,,,,,Switzerland,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2021 +C12379,315637,"Covid-19, Universal Health Coverage, and the Kenyan health system: a collaborative ethnographic study",,2021,-99,"Institute for Health and Society, University of Oslo",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Africa,Africa,,,,Kenya,Kenya,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery, +C12380,315472,"CO-DUTIES: Democratic Duties, Collective Action, and the Greater Good after COVID-19",,2021,-99,INSTITUTT FOR FREDSFORSKNING,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C12381,314578,"Media Use in Crisis Situations: Resolving Information Paradoxes, Comparing Climate Change and COVID-19 (MUCS)",,2021,-99,Institutt for informasjons- og medievitenskap,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Policies for public health, disease control & community resilience",Communication, +C12382,315769,"Employment, investment, and inequality in the aftermath of the Covid-19 crisis",,2021,-99,"NORGES MILJØ- OG BIOVITENSKAPELIGE UNIVERSITET (NMBU), School of Economics and Business",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C12383,315580,Covid-19: Digital Politics and the Role of Expertise,,2021,-99,Senter for vitenskapsteori,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C12384,315008,"The Corona-crisis, structural change, and macroeconomic policy",,2021,-99,STIFTELSEN HANDELSHØYSKOLEN BI,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts, +C12385,315422,"Nordic labour market models facing pandemic crisis: A comparative study of policy responses, actor adjustments, and social outcomes",,2021,-99,FORSKNINGSSTIFTELSEN FAFO,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C12415,20/09064-5,Cardiorespiratory telerehabilitation for patients after hospitalization for COVID-19 in Brazil: randomized clinical trial,"Introduction: Although there is a lack of studies with specificities regarding post-COVID 19 clinical condition, patients who survive the acute condition are likely to suffer with post intensive care syndrome. Hence, they may experience respiratory, motor and psychological impairments, which should be addressed by long-term rehabilitation programs (RP). These programs aim to increase the chances of recovering from this syndrome. However, the offer to RP is worrying nationally and internationally, since, even in non-pandemic periods, there is an important deficit in the number of rehabilitation center opportunities. Considering the increase in the need of rehabilitation after COVID-19, there may happen a collapse in RP system. Moreover, there is a lack of consensus regarding the time after symptoms disappearance patients are still contagious, thereafter, distance RP (telerehabilitation) presents as an adequate tool, however, it must be tested before its implementation. Objectives: Study 1: to characterize physiological responses during the execution of activity daily life (ADL) in patients post-hospitalization for COVID-19. Study 2: to verify the effectiveness of cardiorespiratory telerehabilitation protocol in patients after COVID-related hospitalization. Methods: Individuals after COVID-19 related hospitalization will be assessed regarding eligibility criteria. For sample size will be executed a pilot study. Study 1 will be a longitudinal observational study and study 2 will be a randomized controlled trial coordinated by the Physiotherapy Department of the Federal University of São Carlos regarding a virtual domiciliary RP involving accessible and functional activities. The primary outcome will be functional capacity verified by physical tests. Expected results: we expect with study 1 to understand post-COVID-19 patient's PADL through an analysis of physiological variables after hospitalization and, with study 2 we expect to find and effective and accessible virtual RP with individualized prescription, thus increasing the access to PR benefits such as improvements in functional capacity and quality of life of patients after COVID-19 infection. (AU)",2021,2023,"Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil",,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Randomized Controlled Trial | Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C12416,20/06725-0,Serum vitamin D levels in COVID-19 patients: prevalence of hypovitaminosis and associated factors,"In December 2019, a new coronavirus was identified in Wuhan, China, as the agent of respiratory infections, including cases of respiratory failure and death. The virus called SARS-CoV-2 spread rapidly to more than 180 countries, including Brazil, causing an international alarm and pandemic declaration by the World Health Organization. However, despite the epidemiological importance, additional information on SARS-CoV- 2 are necessary to better understand the transmission, pathophysiology, disease severity factors and risks for the general population. Vitamin D has immunomodulatory properties, including the regulation of inflammatory cytokines, and may have a preventive role in the evolution of acute lung injury. It is plausible that vitamin D may have a protective role against SARS-CoV-2, reducing the severity of pneumonia and the progression to acute respiratory distress syndrome. However, there are no studies on the prevalence of hypovitaminosis D and the factors associated with this condition in the population of people infected with SARS-CoV-2. Considering this knowledge gap, the present study aims to assess serum vitamin D levels in hospitalized patients with SARS-CoV-2 infection, as well as to identify factors associated with this deficiency, especially inflammatory and oxidative stress variables. The project is an observational, cross-sectional study with patients of both sexes, aged 18 years or older and hospitalized with suspected SARS-CoV-2 infection. (AU)",2021,2023,"Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Disease pathogenesis,2021 +C12417,20/14062-1,Nano-Biointerface studies of mucus-modulating particles containing Remdesivir with respiratory epithelium membrane models in healthy and hyperinflammatory conditions of COVID-19,"The most serious cases of COVID-19 are manifested by a state of pulmonary hyperinflammation caused by a cytokine storm, which occurs due to the infection of the lower airways by the SARS-CoV-2 virus. Under these conditions, diffuse alveolar damage leads to severe acute respiratory disease (SARS), with a high mortality rate. Mucus-modulating nanoparticles are potentially useful in the pulmonary administration of drugs and vaccines for the treatment of COVID-19, as they could be designed to overcome the mucus barrier present in the airways and reach the alveolar region, which is covered by the lung surfactant barrier. Thus, the therapeutic and / or preventive success of these carriers depends on interactions occurring at the nano-bio interface of these two barriers present in the pulmonary administration route. The objective of this project is to characterize the nano-biointeractions of mucus-modulating particles containing the model drug remdesivir with real and biomimetic membranes of the respiratory epithelium. The studies will be performed with cells able to producing mucus and lung surfactant. These biointerfaces are relevant to SARS-CoV-2 infection and represent important sites for the release of remdesivir. The characterization of the biophysical properties of biological membranes (extracted from epithelial cells) and biomimetics (produced with synthetic lipids) will be performed using Langmuir films and phospholipid vesicles in the presence of particles in healthy and inflammatory conditions. The project conclusion will allow us to gain mechanistic insights into the main interactions occurring in these nano-biointerfaces that can fundamentally improve the rational design of mucus-modulating particles for pulmonary administration of drugs and vaccines for the treatment of COVID-19 and other serious respiratory syndromes. (AU)",2021,2023,"Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C12418,20/09681-4,Development of the new viral vaccine strategy against SARS-COV-2,"The Covid-19 pandemic has mobilized researchers all over the world for the purpose of developing technology to fight against the coronavirus. The Sars-Cov2 belongs to a coronavirus family which affects people and animals all over the world, it can cause common colds to severe respiratory diseases such as the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS). After a few cases of atypical pneumonia at the end of 2019, the disease disseminated globally, showing high rates of transmission, leading the WHO to declare Public Health Emergency of International Concern, in January 2020, and it was considered a pandemic on March 11, 2020. Many countries have decided to adhere to social distancing as the only alternative to control the transmission rates of the disease, and thus, avoid overwhelming health care services. However, the different levels of restrictions led to a global depression in economies around the world. Several initiatives have been developed to contain the virus and its effects through the economy and health, but the development of an effective vaccine is the technology that will bring the greatest impact to control this pandemic. Intra-muscular vaccines are among the vaccines in development that are most promising. In this project, the proposal is to develop a vaccine based on Salmonella enterica Typhimurium carrying viral proteins against Sars-CoV-2, given that we own the technology and master the vaccinal process with proven effectiveness for other diseases such as Rhodococcus equi, in which our vaccine has been successful through immunization protocols with one or two oral doses or even with a single nasal dose, being capable of protecting mice against experimental with the induced infection agent, leading to cells immunization, systemic humoral and mucous with generation of immunological memory. In this proposal, the developed vaccines will be administered orally or intranasally, in order to facilitate production processes, bring low operation cost, decrease the contamination risks observed for the injected vaccines, enabling large-scale use. Our proposal, if successful during the entire development cycle, will come at following stage to the vaccines that have already been developed. (AU)",2021,2022,Invent Biotecnologia Ltda. - ME,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C12419,21/03661-4,Application of artificial intelligence to aid in the diagnosis and prognosis of SARS-CoV-2,,2021,2021,Lablift Ltda,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Innovation,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C12420,20/06190-0,Drug repurposing and search of selective inhibitors for human dihydroorotate dehydrogenase as a strategy in fighting against COVID-19,"No longer than four months ago, the world was not aware of the existence of the virus SARS-CoV-2. Today, this virus, responsible for COVID-19, has already spread around the all planet, infecting more than 2 million people and killing more than 150 thousand. The pandemic caused by COVID-19 has led to the collapse of both economic and the health systems around the world. So far, social distance is the only weapon available to minimize the impact of the virus proliferation. There is no vaccine available to prevent the infection caused by SARS-CoV-2, neither an effective treatment for COVID-19. In this context, this proposal aims at contributing to the development of an innovative therapy against COVID-19, either through drug repurposing or by identifying new chemical identities, all based on the selective inhibition of the human enzyme dihydroorotate dehydrogenase (HsDHODH). HsDHODH, which, takes part of the de novo pyrimidine biosynthetic pathway, is the pharmacological validated target for proliferative and parasitic diseases, and have been considered an attractive target for the development of antivirais. The fact that the virus relies on the host cell biochemical machinery to provide nucleosides for its viral replication cycle makes enzymes involved in the biosynthesis of nucleosides, such as HsDHODH, potential targets for the development of broad spectrum antivirals. Our studies include enzymatic and biophysical assays, citotoxicity tests using different mammal cells, antiviral assays in cell culture using a biosafety level 3 laboratory and synthesis of drugs and analogues based on virtual screening studies. Our project put together research leaders in complementary areas, contributing not only to accomplish our goals, but also to consolidate a complex and multidisciplinary pipeline in drug discovery. (AU)",2021,2023,"Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C12421,20/12915-7,COVID-19 and mental health: cultural adaptation and validation of instruments for the Brazilian context,"The COVID-19 pandemic is the biggest public health emergency facing the international community in decades. In addition to concerns about physical health, it also brings concerns about mental health, since psychological suffering can be experienced by the general population and by the health professionals involved, directly impacting their quality of life. The intensification of feelings such as fear, anger, stress, insecurity and frustration are associated with an increased risk of developing psychiatric disorders. In this context, the availability of measurement instruments related to COVID-19 and Mental Health, adapted and validated for the Brazilian context, is of great relevance, as for measuring anxiety (COVID Anxiety Scale - CAS) and the threat perceived by COVID-19 (Perceived Coronavirus Threat Questionnaire -PCTQ) and the impact of COVID-19 (Coronavirus Impacts Questionnaire - CIQ). They are instruments that have shown reliability and validity in their original version, developed in other cultures, such as India and the United States and that, through this study, will be made available in Brazil and may guide the conduct taken by health professionals and competent authorities, and the elaboration of public health care policy plans, aiming to prevent the population's injuries. In view of the above, the present study has the general objective of translating, adapting and validating CAS, PCTQ and CIQ for the Brazilian context. This is a methodological study, which will respect the steps recommended by Beaton et al. (2000), which are: translation, synthesis of translations, back-translation, evaluation by a committee of experts, pre-test, presentation and evaluation of reports on the process of cultural adaptation and analysis of the psychometric properties of these instruments. The researchers who developed the tools authorized the process of validating them in Brazil and are associated researchers in the proposal. All ethical precepts will be respected and the project was submitted to the Research Ethics Committee of the Federal University of São Carlos (UFSCar). The development of this study will enable several results, such as the availability of several instruments related to COVID-19 and Mental Health. In addition, it will enhance the international partnership of the proposing researcher with new international research groups of excellence in the subject investigated. The stages of data collection will be carried out online, after the free and informed consent of the participants (in different stages), with the completion of the data collection instruments through google forms, being disseminated at national level, respecting the eligibility criteria previously established. Statistical analyzes will be carried out at different stages of the research, such as descriptive, correlation and confirmatory factor analysis, among others, in order to verify the evidence of reliability and validity of the Brazilian version of the instruments analyzed. It is important to highlight that the proposed research project is original, innovative, with great scientific relevance and notorious applicability for the current pandemic context that we are experiencing. (AU)",2021,2023,"Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil",,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C12422,20/12610-1,Development of colorimetric detection using a molecular biology and nanotechnology platform for the rapid diagnosis of COVID-19,"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the agent of Coronavirus Disease 2019 (COVID-19). The transmission occurs through contact with contaminated surfaces, aerosol inhalation or through spills and secretions. Between the 5th and 14th day: fever, dry cough, tiredness, sore throat, headache, diarrhea, loss of smell and / or taste may appear as symptons. In severe cases: shortness of breath, chest pain or pressure, speech loss and movement disability are mostly associated with comorbidities. The disease reached pandemic status within a large number of deaths. The main methodologies for diagnosis are the fast test (sensitivity 70%) and RT-PCR (sensitivity 99%, which has a higher cost). Diagnosing and tracking patients is important to decrease the spread and allow a safe return of economic, educational, leisure and sports activities. The objective is to develop a sensitive, specific, simplified and accessible test by colorimetric detection of SarsCov-2. Nasopharynx and saliva samples from patients with COVID-19 are going to be collected. In microtube 1, the RNA will be extracted. In microtube 2, reagents will be added for cDNA and RT-PCR synthesis plus thiolated primers (regions: Spike, RNApol and Nucleocapsid), after it, the samples will be subjected to thermal cycling in the dry bath. Afterwards reagent 3 (reading) will be added, which contains gold nanoparticles. The color change from red to blue will be observed when the genetic material is detected by two principles: RT-PCR (exponential increase of the target genes) and Nanotechnology (thiolated primers at the ends of the amplicon will react with nanoparticles occurring the colorimetric reaction). The results of this project will be a low-cost qualitative and quantitative solution with an early and assertative diagnosis of symptomatic patients and identification of asymptomatic patients. Contributing to the planning of public policies in concearn to the treatment and mitigation of contagion. (AU)",2021,2023,"Centro Universitário Saúde ABC. Fundação do ABC. Santo André , SP, Brazil",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C12423,20/13480-4,Virtual screening and in vitro and in vivo evaluation of nicotinic receptors as a therapeutic target for SARS-CoV-2: focus on interaction with ACE2.,"SARS-CoV-2 (Severe Acute Respiratory Syndrome, Coronavirus 2) is the virus that causes COVID-19 (Coronavirus disease 2019), declared as a pandemic in March / 2020, which in its severe form leads to death due to acute lung injury (ALI), refractory hypoxemia and the presence of microthrombi. The virus enters the cell after binding the Spike protein to ACE2 (angiotensin-converting enzyme 2). There are no vaccines and specific treatment so far, the death from COVID-19 is still high and a second wave is beginning to occur in several countries. Nicotinic acetylcholine receptors (nAChRs) appear as a potential therapeutic target. Our hypothesis is that nACRs can participate not only in the capacity for viral invasion since it can be related to an expression of ACE2, but also with a modulation of the inflammatory process. The project aims to elucidate whether from this the nAChRs can be involved in COVID-19 and search for drugs already available with the potential positive modulatory effects in these receptors. An in vitro model of SARS-CoV-2 infection will be used in pulmonary epithelial cells (BEAS and A549) with and without ACE2 overexpression. In vivo, animals with cholinergic deficiency will be submitted to LPS instillation (pulmonary) or intestinal ischemia and reperfusion (extrapulmonary) to mimic a cytokine storm and ALI, and the role of these receptors and their relationship with the expression of ACE2 will be evaluated regarding inflammatory response. Parallel to this, through virtual screening, drugs with the potential for modulation of these receptors that can be subsequently tested model models will be identified. We expected to elucidate whether nAChR can be a therapeutic target for COVID-19 and to point out drugs already available and useful for immediate use. (AU)",2021,2023,"Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C12424,20/06445-8,Dinamics and impact of respiratory infections due to SARS-CoV-2 and other respiratory viruses in individuals with cystic fibrosis,"Patients with cystic fibrosis (CF) have suppurative and recurrent pulmonary manifestations. Some respiratory viruses may have a greater impact on these patients, and previous studies have indicated a significant role for rhinovirus C and also for coronavirus subtypes, such as NL-63. Hypothesis: Pediatric CF individuals will have low clinical manifestations of SARS-CoV-2 infection, when compared to adult CF individuals. A different immune response is expected among children and adults with CF during SARS-CoV-2 infection, including cytokine expression profile and markers such as CD-26 (dipepty peptidase 4) in peripheral blood. Methods: Approximately 150 patients (75 adults and 75 pediatric) will be approached during routine consultations and during acute respiratory exacerbation to collect samples of respiratory secretion, blood sample and perform usual clinical consultation / pulmonary function markers and pulse oximetry, according to the outpatient clinic routine (ICr-HCFMUSP and INCOR-HCFMUSP). Molecular point-of-care tests (commercial panels) will be used for identification of respiratory viruses and SARS-CoV-2. Samples with picornavirus detection will be subjected to real-time PCR specific for rhinovirus and enterovirus D68, and sequencing of the positive samples for rhinovirus will be done to determine the species. The peripheral blood samples will be used to evaluate the immune response, profile of circulating cells and cytokines, presence of antibodies to SARS-CoV-2 and P. aeruginosa, and also presence of antibodies to other species of coronavirus by plaque reduction neutralizing tests (PRNT). Samples with identification of SARS-CoV-2 will be subjected to genome sequencing for epidemiological purposes. The main clinical outcomes assessed will be acute pulmonary exacerbation, hospital admission, acute (or acute) respiratory failure, appearance of new bacterial pathogens. (AU)",2021,2023,"Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil",,Human Populations | Viruses,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +C12425,20/12920-0,Application of natural SARS-CoV-2 proteins to aid the development of new diagnostic strategies for COVID-19,"COVID-19 represents an unprecedented pandemic and tends to become endemic and recurrent due to the characteristics of the SARS-CoV-2 virus and its mutations. With the continuous increase in the number of cases worldwide, the lack of vaccines or effective treatments, the health system is significantly impacted by the high demand for resources to diagnose and treat patients. To understand the infection and fight the pandemic, detailed characterization of SARS-CoV-2 structural proteins primary structure, post-translational modifications, interactions and antigenicity are essential. Pathophysiology and virulence mechanisms of SARS-CoV-2 have been associated with the structural elements, spike (S), membrane protein (M) and envelope (E) proteins. Particularly the glycoprotein S plays important role in viral attachment to the ACE2 receptor in the surface of the host cell, fusion and entry, process depend on specific post-translational modifications to promote virulence. These characteristics in S protein and potentially in other structural proteins are mediated by the constant mutations in viral RNA. These mutations and resulting pos-translational modifications also produce cleavage sites and neo-epitopes that have immediate applications to improve the specificity and sensibility of diagnostics approaches. Here, we seek to explore a combination of biochemical approaches to characterize structural proteins of SARS-CoV-2 as well as its interactions with host cells. After identification and selection of important regions on surface and membrane proteins, we will develop affinity agents and mass spectrometric based approaches to detect and quantify the virus with high sensitivity and specificity. To achieve this general goal, we propose: i) to characterize in detail by mass spectrometry the natural viral proteins obtained from patient samples and recombinant proteins submitted to infection models, with a focus on possible post-translational mutations or modifications; ii) express and purify important domains of SARS-CoV-2 Spike (S), E (envelope) and M (membrane) proteins; iii) identify and synthesize peptides that represent important antigens and are responsible for interacting regions with host cell proteins; iv) produce synthetic heavy variable chain antibodies using phage libraries against natural proteins, expressed domains and selected synthetic peptides; v) scale-up the production of recombinant proteins, synthetic antibodies and peptides and conjugate them with particles to allow a wide exploration of interactions, as well as multiplex diagnostic platforms and rapid assays. Inevitably, developments from this project may also translate into potential therapeutic molecules or vaccine candidates, based on their cell infection neutralizing capabilities or high antigenicity response. More importantly, with a strong collaborative mindset, we will make available these scaled-up molecules for parallel initiatives focused on COVID19 diagnostics, therapy or vaccines, in order to speed up national technological developments and promote, at a least in part, independence from international markets. In summary, the combination of local expertise and a network of specialists and relevant clinical samples, we strongly believe that this effort greatly increases the chances of providing timely and successful answers to the demands in diagnostic of COVID19 in a moment of limited resources and great suffering worldwide. (AU)",2021,2023,"Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Immunity",2021 +C12426,20/08779-0,"Telerabilitation as an alternative to pandemic COVID-19 and its effects on functional capacity, mental health and quality of life of older people with Alzheimer's disease: a randomized and controlled clinical trial","The emergence and increasing incidence of severe acute respiratory syndrome - coronavirus 2019 (COVID-19), presents unprecedented new challenges to clinical practice and research worldwide. Social distancing has been an effective measure to control the rate of viral transmission and studies predicted that social distancing might be prolonged or intermittent until 2022. The populations with the highest mortality due to COVID-19 are older people and vulnerable people. Older people with comorbidities due to primary neurodegenerative disorders, such as Alzheimer's disease (AD) and their caregivers, deserve special attention in this pandemic scenario. Telerehabilitation (RT) can be remote alternatives of clinical and professional support for people with AD and their caregivers. Objective: To analyze the characteristics and effects of a telerehabilitation program on mental health, functional capacity and quality of life statuses of people with AD and their caregivers that will be undertaken during social distancing due to COVID-19. Methods: Forty-eight people with AD (mild and moderate stage) and their caregivers will be invited to answer a structured questionnaire in regards of social distancing and also will be evaluated for mental health, functional capacity and quality of life. The volunteers will be randomized and allocated into two groups, Telerehabilitation and Control and followed for 12 weeks. Participants will be assessed at baseline, immediately after (week 13) and follow-up (week 24). Expected results: It is expected that people with AD and their caregivers will present high adherence to the telerehabilitation program and the program will be beneficial at improving their mental health, functional capacity and quality of life statuses. (AU)",2021,2023,"Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Caregivers | Health Personnel,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C12427,20/05264-0,SARS-CoV-2 VLP production,"The beginning of 2020 saw the outbreak of the COVID-19 caused by a new coronavirus, the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2). A better understanding of this new virus and the development of ways to control its spread is imminent. In this study, we intend to test an already established VLP production platform using the baculovirus-based on gene expression system. Initially we propose to express 4 genes of the SARS Cov-2, the gene of the Nucleocapsid (N), Envelope (E), Spike (S) and Membrane (M) proteins, these being in 4 different bacmids. This provides us with the flexibility to test different MOIs, different combinations and even combinations with proteins from other CoVs, opening the possibility to search for universal VLPs for CoVs. In addition, it is our expectation to use epitopes of these same proteins for immunogenicity tests. VLP-SARS CoV-2 may be studied not only for the production of vaccines, but also for safe biological material for the production of diagnostic kits, the production of hyperimmune serums and other immunobiologicals. Thus, our studies may provide biological material that can help guide experimental efforts for the development of vaccines against SARS-CoV-2 and other CoVs that exist or may arise in the future. (AU)",2021,2023,"Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil",,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +C12428,20/13240-3,Functional validation of a cis-regulatory element associated with coagulation disturbances and severe COVID-19,"Although there is an accelerated advance in the knowledge of the COVID-19 pathogenesis, the causes that lead patients to respond in different ways during the evolution of this disease are poorly known. Enhancers are cis-regulatory elements which are the main determinants of the specificity of gene expression in different cell types. In addition, enhancers are considered important regions hotspots to genetic predisposition to diseases. Based on public data, mainly from: Genome-wide association studies (GWAS), High-throughput chromosome conformation capture (Hi-C), Chromatin Immunoprecipitation with sequencing (ChIP-seq), and regions DNAse I hypersensitive sites, we collected evidence which indicate that a genetic variant associated with severe COVID-19 is located within a putative enhancer of a gene previously associated with coagulopathies. Therefore, in this project we propose to carry out functional assays (ex: capture of chromatin conformation - 3C, in vitro enhancer activity through luciferase reporter, ChIP-qPCR, ATAC-seq, deletion of the enhancer region using CRISPR / Cas9 technology, and in vivo enhancer activity through the generation of transgenic mouse embryos) to evaluate if the enhancer predicted by in silico analyzes, participate of the transcriptional regulation of the gene associated with coagulopathies cited above. The execution of this project may bring new knowledge about the genetic and epigenetic role in the normal coagulation process, as well as coagulopathies and COVID-19 pathogenesis. (AU)",2021,2023,"Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil",,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C12429,20/07957-2,Study of the prevalence of neuropsychological deficits in patients recovered from COVID-19 associated with post-intensive care syndrome,"It is estimated that approximately one third or more of ICU survivors develop continuous and persistent cognitive impairment. As for patients with acute respiratory syndromes such as Covid-19, the prevalence of persistent cognitive impairment is even higher and can reach 78% in 1 year and 25% in 6 years. The literature has treated this phase of post-intensive care syndrome from English Post-intensive care syndrome (PICS), which describes, impairment of psychological health (emotional and cognitive) and physical function of patients who required ICU care. The aim of this study is to evaluate neuropsychological aspects in patients recovered from COVID-19. Method: Observational study that will use a digital platform containing a brief questionnaire of sociodemographic data and information on Covid-19 contamination and a neuropsychological battery with measures of attention, memory and executive functions, in addition to depressive and anxious aspects. It is intended to evaluate a sample of more than 500 participants for the composition of three groups: Light, Moderate and Serious Symptoms (treated in the ICU). The results of this study are expected to provide a cognitive overview of the sample to support the development of neuropsychological rehabilitation programs for patients with Covid-19 cognitive sequelae. (AU)",2021,2023,"Diretoria de Pós-Graduação e Pesquisa. Universidade Metodista de São Paulo (UMESP). Instituto Metodista de Ensino Superior (IMS). São Bernardo do Campo , SP, Brazil",,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,"Post acute and long term health consequences | Supportive care, processes of care and management",2021 +C12430,20/13381-6,"Detection, viral load and phylogenetic analysis of SARS-CoV-2 in samples of volunteers from the vaccine ChAdOx1 nCoV-19 clinical trial","In 2019, a new coronavirus, SARS-CoV-2, was recognized as the cause of an outbreak of respiratory syndrome, COVID-19, causing millions of deaths worldwide, thus reaching pandemic status. Given this scenario, several vaccines are being developed, with emphasis on the vaccine ChAdOx1 nCoV-19 (AZD1222), developed by the Oxford Jenner Institute, in the University of Oxford, United Kingdom, the first one to start phase III clinical trials which started in Brazil, in June this year. In this study, voluntary participants are randomly divided into two groups. One group receives the ChAdOx1 nCoV-19 vaccine and another group (control) receives the vaccine for Meningitis. During the period of one year, vaccinated participants who present symptoms will be invited to collect nasopharyngeal and oropharyngeal swabs in order to detect SARS-CoV-2 by RT-PCR in real time. The samples will also be tested for other respiratory viruses including Influenza A and B, Respiratory Syncytial Virus, Rhinovirus and Adenovirus for differential diagnosis, contributing to epidemiological surveillance data, as well as observation of possible cases of co-infection. Positive samples will also be subjected to new generation sequencing (NGS), allowing the investigation of evolution events, mutation analysis, possible events that favor gain-of-function and trace the origin of the SARS-CoV-2 variants in the immunized population. From the molecular results and data obtained from the patients, statistical analysis will be performed by the Two-way ANOVA test using Graphpad Prism version 8.0, considering statistically different a p value <0.05. (AU)",2021,2023,"Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Vaccine logistics and supply chains and distribution strategies",2021 +C12431,20/10097-5,Assessment of the integrity of the intestinal epithelial barrier in patients infected with SARS-COVID-2: a multicenter study,"Changes in functioning of the gastrointestinal tract (nausea, vomiting, diarrhea and abdominal discomfort) have been described in pandemics by coronavirus in 2003 and 2019. Accordingly, experimental data in rodents confirm that respiratory viral infections promote disorders of the intestinal functions including increased motility, loss/malabsorption of fluids, inflammation of the intestinal mucosa and changes in the composition of the microbiome. In addition, patients who have gastrointestinal symptoms at the initial phase of SARS-CoV-2 infection have a worsening of their clinical condition, with increased need for intensive care procedures, higher fever and mechanical ventilation. However, there are no reports whether in these pathological conditions there is an impairment of the barrier function of the intestinal mucosa. In several other pathologies (sepsis, inflammatory bowel diseases, celiac disease), the rupture of intestinal tight junctions may turn the intestine into a source of potentially pathogenic microorganisms, contributing to the worst clinical prognosis, activation of the systemic inflammatory response and development of secondary bacterial infections. For these reasons, the present study proposes to evaluate, for the first time, the integrity of the intestinal epithelium in patients infected with SARS-CoV-2, by the quantification of biomarkers and bacterial translocation in the systemic circulation and also in urine. (AU)",2021,2022,"Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Disease pathogenesis,2021 +C12432,20/08239-6,"Emotions, mood and coping strategies in the Coronavirus pandemic","The aims of the study are i. to collect information regarding aspects related to the mental health of university students and the general Brazilian population considering the current context of the coronavirus (COVID-19) pandemic; ii. to collect information about these aspects in a convenience population in the United States of America (USA); iii. to verify the measurement invariance of the psychometric instruments between independent samples (according to demographic characteristics) and different countries (Brazil x USA); and iv. to estimate the impact of emotions and mood on pandemic coping strategies adopted by adult Brazilian and North American individuals. This is a cross-sectional study. The Depression, Anxiety and Stress Scale-21 (DASS-21), the Impact of Event Scale-Revised (IES-R), the Brunel Mood Scale (BRUMS) and the Brief COPE Scale will be used as measurement instruments. The validity and reliability of the data will be evaluated by confirmatory factor analysis and coefficient omega, respectively. Measurement invariance of the factorial model of each instrument applied to the different samples (student x general population, states and other characteristics of interest) will be analyzed using multigroup analysis (deltaCFI). The transnational invariance will also be analyzed. The mean scores for depression, anxiety, stress, mood changes and coping strategies will be calculated by point and by 95% confidence interval considering the total sample and other subsamples. The impact of emotions and mood on the coping strategies used by individuals will be estimated using a structural model. The evaluation of this model will be carried out in two steps. In the first step, the goodness-of-fit of the model to the data will be evaluated using X2/df, CFI, TFI and RMSEA. The Weighted Least Squares Mean and Variance Adjusted (WLSMV) estimation method will be used. In the second step, the significance of the hypothetical trajectories (b) of each independent variable will be evaluated using the z-test (significance level = 5%). The qualitative analysis of the answers given to the open answer questions will be carried out through content analysis and elaboration of the discourse of the collective subject (DCS). (AU)",2021,2023,"Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C12433,21/00930-4,Evaluation of pulmonary tissue damage in viral infection (SARS-CoV-2 and/or Influenza),"Respiratory syndromes are associated with lung endothelium damage. Recently, the SARS-CoV-2, the main cause of Coronavirus Disease 19 (Covid-19) was associated with several lung endothelium damages, including alveolar dysfunction. Also, regarding pulmonary injury, immunological response leads to a complex inflammatory response from resident cells into the respiratory tract. The balance between the capacity of crossing off pathogens and extension of the inflammatory response are crucial factors to succeed in the infection control by the host. Cellular communication is essential for the thriving of an organism as a whole. Behavioral cues for individual cells come from the cellular microenvironment as well as other cells or soluble mediators. Activation of these receptors by their ligands triggers cellular effects through activation of intracellular signal transduction pathways, which in turn relies heavily on post-translational modification of proteins. In particular protein, phosphorylation is a pivotal modification mechanism, based on fast and reversible covalent binding of a phosphoryl moiety to specific amino acid residues in proteins. Despite the main actors on immune innate and adaptive, platelets have been highlighted as an auxiliary actor on infections and inflammation. Further, we purpose to investigate: (i) tissue damage from lung and vascular by viral infection by in vitro model; (ii) platelet function as immune cells. The investigation of signaling transduction of vascular and pulmonary damage will be performed by RNA and protein expression/activation and validated on confocal microscopy. To drive the contribution of platelets on the immune and inflammatory response will be evaluated by co-culture between vascular or lung cells pre-incubated with Influenza and/or SARS-CoV-2. (AU)",2021,2022,"Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C12434,21/01560-6,Counterproductive behaviors in coping with the SARS-Cov-2 pandemic in Brazil: investigation using a 10-year follow-up cohort and ecological momentary assessment,"The SARS-CoV-2 pandemic requires several changes in the behavior of each individual so that there is less impact on the entire society. Thus, it is possible to identify behaviors that can aggravate the spread of the virus, called counterproductive behaviors. It is possible that individual aspects (such as personality traits) and social and environmental factors (socioeconomic level, education, etc.) prior or current to the pandemic, are associated with such behaviors, representing risk factors for greater vulnerability to contamination. However, it is very difficult to systematically assess the impact of these aspects, as longitudinal studies that have evaluated individuals previously and during the pandemic are necessary. The Projeto Conexão cohort (BHRCS) is in a privileged position to investigate risk factors for counterproductive behavior. The study has followed 2,511 children and adolescents since the year 2010. Today, aged between 16 and 25 years, these subjects were evaluated with an extensive protocol on psychic symptoms, temperament traits and socioeconomic characteristics in an attempt to understand the developmental trajectories of mental disorders. This proposal aims to expand the previously used method of intensive collection (Ecological Momentary Assessment) to assess counterproductive behaviors and associated factors when facing the pandemic. In this way, we will be able to assess and predict which individual and environmental factors predict counterproductive behaviors. (AU)",2021,2022,"Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C12435,20/12143-4,"Disaster plan implemented in the Covid-19 pandemic - actions, results and lessons learned","The rapid expansion of the COVID-19 pandemic in the world caused the need to adopt new strategies for the organization of health systems and services. In a scenario where the demand quickly exceeded the usual capacity of health services, especially in relation to beds in intensive care units (ICU), there was an urgent need to increase this structure and offer it to the network. In this context, on January 29, 2020, the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HCFMUSP) activated its Disaster Plan to face the pandemic. With the progressive increase in the number of cases in São Paulo, the Crisis Committee of HCFMUSP decided to isolate its Central Institute (ICHC) to serve these patients. Thus, 300 exclusive ICU beds were mobilized for cases of COVID-19, which corresponds to 10% of the total ICU beds for this purpose in the public health network in the city of São Paulo. From March 30 (date that marked the beginning of this movement) until July 31, 2020, more than 3,900 suspected cases of COVID-19 were treated at the ICHC. It is possible and desirable to make a thorough review of the disaster response that has been implemented. Although the primordial role of the strategy adopted by the HCFMUSP Crisis Committee in the response and containment of the epidemic by COVID-19 in the state is notorious, it is essential that this strategy is documented and evaluated in a systematic way. This review after the most critical months of the epidemic in São Paulo will allow the effectiveness of the strategies adopted to be considered, as well as the limitation of others, identifying those that should be incorporated into the Disaster Plan for future confrontations. Thus, this project aims to analyze the Disaster Plan implemented at HCFMUSP in the context of the COVID-19 epidemic, the results obtained from different perspectives (activation, service management in the context of capacity expansion, quality of care, comparative analysis with Plans tertiary university hospitals) and the limitations faced. The study is the report of the implementation of the HCFMUSP Disaster Plan, based on the review of meeting minutes, reports and documents produced, as well as the experience of the proponents - members of the HCFMUSP Crisis Committee, in addition to the quantitative analysis of epidemiological data and assistance. The epidemiological description of suspected cases of COVID-19 will be made based on information from the epidemiological surveillance center and the institutional database - COVID-19 from HCFMUSP. All suspected cases of COVID-19 admitted to the ICHC between March 30 and July 31, 2020 will be included in the study. The analysis of the impact of the Disaster Plan on the health network of the State of São Paulo will be made based on the analysis of CROSS System regulation data. The study will enable a systematic and detailed description of all stages of planning and implementing the Disaster Plan in response to the COVID-19 pandemic in a university hospital in the state of São Paulo. From the results found, a technical document will be produced incorporating the prevention and mitigation strategies found to support the activation of the Disaster Plan at future times. In addition, the comparison of the different response strategies implemented by different university hospitals will allow the proposal of a model for structuring large hospitals for pandemics based on the best results obtained. (AU)",2021,2023,"Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2021 +C12436,20/12124-0,Early molecular detection of SARS-CoV-2 in sputum of vulnerable groups suspected of pulmonary tuberculosis,"The World Health Organization (WHO) has decreed the COVID-19 pandemic since March 2020, after the occurrence of countless cases worldwide, caused by SARS-CoV-2. When present, the symptoms of COVID-19 can range from a simple cold to a flu-like syndrome or severe pneumonia. The risk factors and comorbidities associated with COVID-19 still need to be clarified, but it is known that the impact of the pandemic will affect the poorest populations with economic damage to a great extent, impacting global health. The development of severe forms of COVID-19 is associated with some risk factors, including infection by Mycobacterium tuberculosis. For the diagnosis of COVID-19, nasopharyngeal secretion samples are normally used, however there are reports of research in different biological samples, such as sputum, feces and urine paired with nasopharyngeal samples. With the present study, the authors hope to obtain data to evaluate the use of sputum samples in the detection of SARS-CoV-2 RNA in a population of individuals deprived of their liberty, with respiratory symptoms for COVID-19 and / or tuberculosis (TB). With the evaluation of the data obtained in the research, information on the feasibility of using the Xpert Xpress SARS-CoV-2 methodology can be extracted, which allows reducing the diagnostic time of COVID-19. The possibility of using the methodology to be linked to the Rapid Molecular Test Network for TB will be evaluated, as an aid in the diagnosis of COVID-19 in different capitals and municipalities in the country, which may represent an increase in the availability of laboratory diagnosis and early detection of the virus in symptomatic and contact individuals. Consequently contribute to the early adoption of isolation measures and reduction of new infections. (AU)",2021,2023,"Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil",,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C12437,20/12110-9,"Cannabidiol (CBD) in patients with mild to moderate symptoms of coronavirus 2019: a randomized, double-blind, placebo-controlled clinical trial","The aim of this work is to conduct a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of cannabidiol (CBD - 300 mg a day) in patients infected with SARS-CoV-2. The specific objectives are to assess whether, in patients with mild and moderate forms of SARS-CoV-2, daily use of CBD 300 mg for fourteen days is capable of: i) decrease viral load; ii) modify inflammatory parameters, such as cytokines, measured from serum; iii) reduceclinical and emotional symptoms through daily clinical evaluation; iv) improve the quality of life and sleep; v) reduce hospitalization and worsen the severity of the disease; v) Monitor the possible adverse effects of CBD use in these patients vi) Evaluate whether CBD 300 mg can prevent depression, burnout, PTSD and other neuropsychiatric disorders in SARS-CoV-2 patients; vii) Evaluate if CBD can prevent central structural and functional abnormalities in SARS-CoV-2 patients as assessed by DTI diffusion tensor imaging and rsfMRI - resting-state functional magnetic resonance imaging. (AU)",2021,2023,"Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2021 +C12438,20/12165-8,High molecular weight heparin inhalation for the treatment of Sars-CoV-2,"Coronavirus 19 (COVID-19) is a respiratory disease of viral cause that was identified in December 2019 after the first cases in China, spreading rapidly until reaching pandemic status, causing the collapse of numerous health systems and strong impact economic and social. At the end of April 2020, 3.08 million cases and more than 214 thousand deaths were already recorded. The treatment so far has not been established and there are several clinical trials testing known drugs that have antiviral activity in vitro, due to the urgency that the global situation imposes on us. Medicines with specific actions can take years to be discovered, while a vaccine also takes a long time. Recently, it has been shown that the worsening of Coronavirus infection may be related to the formation of micro clots in blood vessels and anticoagulants have been used as adjuvants in the treatment. This study is justified by conducting a pilot study that showed an in vitro antiviral action (anti-COVID-19) of a new high molecular weight heparin. A phase I / II clinical trial will be conducted. In all, 40 participants will be included in two arms. Participants allocated to Group 1 (control). Inhalation with 0.9% saline applied 4-4 hours, for 7 days. Participants allocated to Group 2 (intervention) will receive high molecular weight inhaled heparin (250ug / mL 0.9% SF), at a 4/4 hour dose, for 7 days. The outcomes of interest will be safety (absence of moderate or serious adverse events) and effectiveness (measured in a score of 7 points, with 1 absence of limitations and 7, death). The development of a new therapeutic option for COVID-19 is expected, with the possibility of use in other serious coronavirus diseases, to be subsequently tested in phase III studies. (AU)",2021,2023,"Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial | Prophylactic use of treatments,2021 +C12439,20/12066-0,"The emotional burden of SUS health teams involved in caring for patients with COVID-19: evaluation of the effectiveness of prophylactic measures, including the use of cannabidiol","The objective of this project is to monitor the level of stress and emotional overload of SUS health professionals who participate in the care of patients with COVID-19, evaluating the effectiveness of cannabidiol in reducing stress and preventing mental disorders (Burnout, Acute Stress, Post-traumatic stress, and depression). One hundred two health professionals participating in the care of patients with COVID 19 will participate in the study. For four weeks, all participants will be monitored, and half will receive CBD (300 mg/day in two doses), and the other half will only be monitored (for ethical reasons, the use of placebo was not allowed). The subjects of each CBD / non-CBD group will be selected by lot, through randomization by minimization. We will evaluate the safety and effectiveness of daily use of CBD in reducing stress, preventing depression, burnout, and acute and post-traumatic stress disorder; sleep and temperature patterns (monitored 24h / day by actigraph); in the modification of inflammatory parameters (such as cytokines), genotyping and viral overload. The assessments will vary between daily (mood and actigraph scales), every two days (viral load and temperature), and weekly (scales applied remotely, electronically (App of cell phones - and laboratory tests). The data will be quickly analyzed and, if the use of the CBD shows satisfactory results and with good tolerance, the CBD will be made available to participants who have not used it and wish to do it. The evaluation of safety and effectiveness will be carried out by an independent committee (Monitoring Committee). After the four weeks of CBD use, research participants will be followed for the next 2 months, with the same protocol and without medication, all patients will be reassessed for the presence of mental disorders (SCID-V) and Burnout (ICD-11- Burnout) 12 months after the beginning of your participation in the study. (AU)",2021,2023,"Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C12440,20/12096-6,"Facing COVID-19 pandemic: care management productions, inventions and challenges","The scenario of the health emergency caused by the COVID-19 pandemic imposed new and immense challenges for the managers of the Unified Health System (SUS). The speed and high rate of transmission, the production of serious and fatal cases, and the consequent risk of collapse for the health network, required the establishment of contingency plans. Analyzing the experiences of managers in health regions is of unequal importance given the differences in health, economic, social, demographic and access to health services, particularly in the State of São Paulo, where the disease indicators are significant.Objective: to analyze the productions, inventions and challenges in the management of care implemented by health care networks in two Health Regions of the State of São Paulo to face the COVID-19 pandemic, and to present proposals that can improve the response capacity SUS.Methodology: a qualitative study, type study of multiple cases, will be carried out in 3 phases. The first, of an exploratory nature, will seek to understand how the 63 health regions of the state have been managing network care to cope with COVID-19. It will be developed through a semi-structured questionnaire, to be completed by local and regional health managers. From a first analytical plan, two health regions will be chosen, considering relevance, originality and preliminary results, to be studied in depth, one in the interior and another in the Metropolitan Region of São Paulo.The second phase aims to analyze in depth the productions, inventions and challenges in care management implemented in these two health regions, and will be carried out in three stages:Stage 1 - Document analysis and evaluation of the Contingency Plans and other documents of the state of São Paulo and of municipalities of different sizes that belong to the two health regions.Stage 2 - Mapping of the care management arrangements produced in response to the COVID-19 pandemic, from semi-structured workshops and interviews with regional and municipal health managers, characterizing the specific participation of primary care in coping with COVID-19 and the strategies implemented for populations in situations of social vulnerability. It is also intended to investigate relations with the private sector.Stage 3 - Recognition and analysis of the strategies implemented for (and by) populations in situations of social vulnerability, based on the identification by the municipalities that integrate the regional, of the territories of high social vulnerability. Open interviews and workshops will be held with leaders of social and community movements. This stage of the research aims to seek an approximation to the ways of life and the concrete needs of people and communities. For the analysis of this material, narratives of the experiences reported and / or monitored will be constructed.In the third phase of the study, the results of the investigation will be returned, from shared workshops and seminars, to state, municipal and community leaders, aiming at the elaboration of proposals. Techniques of participatory strategic planning that contribute to the analysis and validation of the findings and proposals that contribute to overcoming the challenges encountered will be used.The study will involve researchers linked to universities, the State Health Secretariat of São Paulo (SES-SP), Municipal Health Secretariats and the Council of Municipal Secretaries (Cosems-SP) in all its phases, through their respective projects. support - Primary Care (SES-SP) and Regional Supporters (Cosems-SP). This methodological strategy will facilitate the production of empirics and the desired construction of effective propositions to face COVID -19.Expected contributions: qualification of the country's response capacity to face the COVID-19 pandemic and the organizational improvement of SUS. (AU)",2021,2023,"Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health service delivery | Health leadership and governance,2021 +C12441,20/12193-1,Development of optical sensors for diagnosis of microvascular reactivity in COVID-19 patients and other severe acute respiratory diseases,"The COVID-19 pandemic has sparked a search for adjuvant and supportive interventions that can improve the clinical outcomes of infected patients. During the acute phase, clinical symptoms of the disease range from asymptomatic infection to severe pneumonia. Severe acute respiratory syndrome (SARS) is the main complication in the critical acute cases, which quite often leads to the need for mechanical ventilation and accounts for more than 90% of the deaths. After the acute phase, the clinical evolution in the medium and long term in survivors is associated with functional sequelae, which may affect quality of life. Long-term sequelae in the subacute and chronic phase of COVID-19 is still poorly understood due to the short-time of the disease. In both the acute and the chronic phases, however, information on tissue oxygenation can be very useful for understanding the clinical course of the disease and predicting outcomes in infected patients. In this context, the present project aims to develop innovative, portable, scalable, reliable and inexpensive technologies that can quantify tissue oxygenation using diffuse optical spectroscopy methods. The devices will be tested in specific clinical protocols for each stage of the disease, which will allow to establish a relationship between the patients' prognosis and disorders in blood microcirculation. Therefore, it is expected that the technology developed in this project will lead to greater optimization of resources for patient treatment and monitoring, which should impact the quality of life of survivors - in addition to decreasing mortality and decreasing the costs of the related health system with morbidities resulting from COVID-19. (AU)",2021,2023,"Instituto de Física Gleb Wataghin (IFGW). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil",,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Innovation,,,Brazil,Brazil,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C12442,20/12140-5,"Changes in regional management strategies in coping with the COVID-19 pandemic and its implications in the health regions of the ""Project to strengthen state health management in the state of São Paulo""","The Covid-19 pandemic has called into check the entire framework of economic policies of the past 40 years, challenging broad responses from the state and social protection policies. In this context, health systems, in their different organizational models, responded more or less quickly and effectively to health needs. All suffered the risks of exhaustion of available resources, either by the abrupt increase in demand, as well as by the progressive loss of self-sufficiency of supplies (medicines, equipment and other materials) and health professionals (mainly doctors and nurses), or by conflicts between political and governmental authorities. In the case of emerging countries, the answers are more difficult, both due to the immaturity or limitations of their social protection systems - including health - as well as the weakness of their economies and the immense inequalities of income and living conditions among their inhabitants - which are evidenced in the context of crisis, both in terms of the provision of services, as well as in the disease's own espraiando. The Brazilian case does not escape the general rule, but, unlike most of these countries, presents a universal model of social protection, established in the Federal Constitution of 1988. However, data updated for Brazil reach more than 4 million confirmed cases and exceed 128,000 deaths (09/09/2020).This project aims, in view of the new pandemic situation of COVID-19, to analyze the responses implemented in health regions under intervention carried out by the SES-SP, in order to strengthen the state health management in five regions, namely, the Metropolitan Region of Campinas, the Ribeira Valley, the North Coast, Itapeva and the Jurumirim Valley. This initiative was designed and planned to contribute to the improvement of the population's health conditions, through the structuring of care according to the RRAS model and also aiming to expand access quality and comprehensiveness of services. For this, the proposed project also has as specific objectives, briefly: i) to identify the behavior of the indicators of evolution of COVID-19 in the 17 RRAS and compare with the epidemiological situation of the five regions of the Project of Strengthening the State Health Management, in the period from January 2020 to December 2021; ii) identify the intervening factors of this result and the changes related to the political dimensions, structure and organization of the networks, constituent components of the previous analysis performed and baseline of the study, and which were altered in the scenario of the COVID-19 pandemic. On the other hand, changes in the profile of contractualizations, regulation and flow of professionals and patients will be identified and analyzed, as well as an indicator of effectiveness based on epidemiological results found in the 5 regions. As a methodological contribution, this is a study with a design of quantitative and qualitative methods using secondary sources of available database, documentary analysis and the use of empirical data through regional workshops, questionnaires and interviews with key informants in the five health regions of the State of São Paulo object of the study. The regional issue in the policies developed by the SUS has been little studied in its complexity and with a more systemic view. The main contribution of the study is the establishment of parameters for the better understanding and improvement of regional and network management and the reduction of the fragmentation of care ensuring the integrality of actions and the improvement of access to the different levels of assistance in the SUS. (AU)",2021,2023,"Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil",,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures | Health Systems Research",Other secondary impacts | Health leadership and governance,2021 +C12484,unknown,Prevention of SARS-CoV-2 transmission in aged care (PreSTAC): Effective evidence-based measures for rapid translation,,2021,-99,South Australian Health and Medical Research Institute Limited,1070881.09,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Infection prevention and control,IPC in health care settings, +C12485,unknown,Accelerated phase I trial of targeted and tunable SARS-Cov-2 spike protein receptor binding domain recombinant protein and mRNA vaccines,,2021,-99,University of Melbourne,1245055.04,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Phase 1 clinical trial", +C12486,unknown,Statin Treatment for COVID19 to optimise Neurological Recovery (STRONGER) trial,,2021,-99,UNSW Sydney,1862373.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments | Clinical trial (unspecified trial phase)", +C12487,unknown,3D-Printed Facial Guards to reduce P2/N95 respirator leak and protect health care workers from COVID-19,,2021,-99,Flinders University,762827.98,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C12488,unknown,Use of Cardioprotective Therapy to Manage Persistent Cardiovascular Effects of COVID-19: A Pathway to Recognition and Treatment of Subclinical Disease,,2021,-99,University of Melbourne,2018497.82,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies, +C12489,unknown,The Pomerium Trial: Protecting Aged Care Residents from the Pandemic via Specialised Nutritional Supplementation,,2021,-99,University of Melbourne,932470.22,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C12490,unknown,"A single dose, globally accessible vaccine to combat emerging SARS-CoV-2 variants",,2021,-99,University of Sydney,1220187.38,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Pre-clinical studies, +C12491,unknown,Accelerated clinical development of a next generation COVID-19 vaccine using the established Sementis Copenhagen Vector platform system,,2021,-99,University of South Australia,1220187.38,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified | Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase), +C12492,GA149258,Photonic Viropsy: Harnessing light on chip for precise SARS-CoV-2 diagnosis,"Progress in nanotechnology is driving the development of analytical tools capable of unlocking the powerful information encoded in biological fluids. Harnessing such precious information will be critical to enabling breakthroughs in the understanding and control of present and future pandemics. The project will tailor and validate a mature yet cutting-edge sensing technology specifically for integrated, precise diagnosis of SARS-CoV-2. This will allow deep insights into how concentrations of serological markers of this virus in symptomatic and asymptomatic patients are associated with the uncontrolled spread of this deadly disease & with significant benefits for addressing current and future pandemic threats to our society and economy.",2021,2022,THE UNIVERSITY OF ADELAIDE,426193.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C12493,GA148819,Clinicians and researchers from Metro North Hospital and Health Service (MNHHS),"Clinicians and researchers from Metro North Hospital and Health Service (MNHHS) and Queensland University of Technology (QUT), Australia will collaborate with researchers from Indian Institute of Science (IISc), India to generate novel Nanotextured materials that inactivate the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The Nanotextures will be fabricated on various materials using technologies such as hydrothermal processing and reactive-ion-etching in Australia and India. Exposure of virus to nanomaterials will be performed at QUT. The project is directed towards the delivery of antipathogenic nanomaterials for healthcare applications such as hospital environments and personal protection equipment.",2021,2022,METRO NORTH HOSPITAL AND HEALTH SERVICE,426193.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,South-East Asia | Western Pacific,,,,Australia,Australia | India,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C12494,GA148995,A study of inflammation in patients whohave recovered from Covid-19 pneumonia,"Inflammation has an important role in the development of cardiovascular disease. COVID-19 is associated with a high rate of lung infection. In this project we aim to study if there are persistent areas of inflammation (on 18-FDG-PET/CT inflammation) in the aorta and lungs in patients who have recovered clinically from COVID-19 pneumonia as it may predict increased risk for future heart disease. If this study shows that persisting lung inflammation is associated with increased blood vessel inflammation, affected patients may require additional treatment to reduce cardiovascular consequences. This project combines the expertise of leading Cardiologists and Nuclear Medicine researchers in Australia and India.",2021,2022,UNIVERSITY OF WESTERN AUSTRALIA,260667.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,Disease pathogenesis,2021 +C12502,NE/V010441/1,National COVID-19 Wastewater Epidemiology Surveillance Programme,"Wastewater-Based Epidemiology (WBE) requires relatively few resources compared to the systematic testing of populations. WBE is especially promising for novel infectious diseases, where asymptomatic cases might play a significant role in transmitting the virus. However, WBE is only now being used to monitor the spread of a pandemic infectious disease. Early studies by ourselves and others have shown that SARS-CoV-2 RNA can be recovered from wastewater, including from wastewater treatment plants (WWTP) preceding local COVID-19 hospitalisation activity. Given the challenge of making available diagnostic tests to the entire UK population, WBE represents a potentially low-cost and immediate mechanism for understanding levels of infection within large geographic areas. N-WESP aims to compare our methods with those of European & North American WBE teams in an inter-lab trial for understanding, supporting and improving the DEFRA COVID-19 measurements which will feed into the Joint Biosecurity Centre (JBC). We will also compare methods with DEFRA, the EA's and JBC whilst they explore options for finer geographical measurements. N-WESP will empower public health authorities with an optimised surveillance tool with maximal sensitivity and predictive power whose uncertainties have been well characterised. N-WESP will determine whether SARS-CoV-2 RNA in wastewater and sludge is infectious, and to what extent there might be downstream risks to human health. N-WESP will exploit catchment and, uniquely, sub-catchment-scale longitudinal surveillance to understand temporal and spatial heterogeneity, relationships to human disease burden distribution and whether there is potential outbreak 'hotspots' by surveilling sewer system nodes.",2020,-99,UK Centre for Ecology and Hydrology,838257.21,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics, +C12504,EP/V014455/1,COVID-19: Investigating Strategies for Mechanical Ventilation in COVID-19 via Computational Simulation of Virtual Patients,"1]. The pathophysiological basis for this disease phenotype is currently unclear. A recent study also noted a significant time-related disease spectrum in COVID-19 patients, with at least two potential ""sub-phenotypes"": Type L, characterized by low elastance (i.e. high compliance), low ventilation to perfusion ratio, low lung weight and low recruitability by imaging; and a Type H, characterized by high elastance, high right-to-left shunt, high lung weight and high recruitability",2020,2021,University of Warwick,442319.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C13647,unknown,Determining the impacts of COVID-19 restrictions on people who use drugs,"""COVID-19 has resulted in unparalleled government interventions to close borders and restrict social interactions which have major implications for illicit drug supply, procurement and use practices, as well as responses,"" Professor Dietze said. ""People who use drugs will be profoundly impacted by COVID-19 and so our study will leverage existing data collections to compare drug use practices and consequences before, during and after the COVID-19 interventions to determine COVID-19 impacts on people who use drugs.""",2020,-99,N/A,324281.75,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,,Western Pacific,,,,,Australia,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C13648,unknown,Sexual & Reproductive Health and Rights in the Asia-Pacific Region - Impact Evaluation of Interruption of Services during the Pandemic,,2020,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,,Western Pacific,Gender,,,,Australia,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery, +C13745,1.04301E+13,BACILLUS CALMETTEGUÉRIN VACCINATION TO PREVENT SERIOUS RESPIRATORY TRACT INFECTION AND COVID-19 IN VULNERABLE ELDERLY - AN ADAPTIVE RANDOMIZED CONTROLLED TRIAL (BCG-PRIME)',"Rationale: On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. Moreover, recent reports demonstrate that mortality rates rise significantly among patients 60 years and older. Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences in vulnerable populations are urgently needed. Bacille Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly. Objective: To determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly. Study design: An adaptive multi-center double-blind randomized placebo-controlled trial. Study population: 5,200 to 7,000 vulnerable elderly, defined as =60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio. Main study parameters/endpoints: The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience in published and ongoing randomized controlled trials in adults and elderly, the risks of BCG vaccination are considered negligible. Vaccination could cause local pain, suppuration and scarring at the site of injection. The size of the trial will ensure rapid availability of results that can inform policy-making during the ongoing pandemic and may be of benefit for participants that received no intervention, as well as individuals who did not participate in the trial.",2021,2022,Utrecht UMC,9537148.68,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments | Phase 3 clinical trial,2020 +C13746,1.043E+13,Prospective cohort study of non-hospitalised COVID-19 patients: determining length of isolation and patient clinical development at home (COVID-HOME study)',"Guidelines on COVID-19 management are developed as we learn from this pandemic. Most research is on hospitalised patients but, the impact on non-hospitalised ones, their clinical evolution, infectiousness, spreading routes and isolation length is not well understood. Studies are scarce, have small sample sizes and contradictory results. A better understanding is needed to properly manage patients isolated at home and improve biosafety guidelines. RESEARCH QUESTIONS 1. To measure the duration and routes of viral shedding, genetic diversity, and development of immunity of non-hospitalised COVID-19 individuals to improve guidelines for biosafety and patient isolation 2. To establish guidelines for the management of COVID-19 patients at home, including early detection of clinical and laboratory predicting factors for severity HYPOTHESIS 1. We expect viral shedding to last longer than 14 days (and differ by specimen) but virus viability to be shorter. They will differ by age and depend on immunity. 2. We expect to predict mild versus more severe clinical evolution using clinical and (changes in) laboratory parameters APPROACH PLAN A prospective longitudinal study of non-hospitalised COVID-19 patients began on 19/03/2020. We expect to enrol 200 individuals during 9 months (including 4 months before funds granted). Consenting people are visited weekly at home to obtain clinical data, a blood sample for laboratory parameters; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion to test for SARS-CoV-2 by RT-PCR. Blood samples are tested for key parameters related to disease severity. Patients are followed on days 7, 14 and 21 after confirmed infection, and if still PCR positive, invited to continue weekly sampling until negative. Household members of infected individuals are invited to join the study. We hope to obtain funds for a further 7 months to perform further sampling, serology, viral genotyping, viral culture and data analysis.",2021,2021,UMC Groningen,514826.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease pathogenesis | Restriction measures to prevent secondary transmission in communities",2020 +C13747,1.043E+13,Evidence-based effective monitoring and control of Covid-19 after the initial outbreak,"The Netherlands, like many countries in the world, is nearing the phase where the social distancing measures that were imposed to control the outbreak of SARS-CoV-2 (the virus that causes Covid-19) will start to be lifted. As there is unlikely to be anything close to herd immunity even in the most affected areas, there is an acute danger that increased mixing of the population when measures are relaxed, as well as importation of cases from outside the Netherlands, can lead to new clusters of cases and a second major outbreak when uncontrolled. Effective monitoring is essential to find new infections, connected to effective protocols for tracing-testing-isolation/quarantine (to be called TTI here) to prevent the new clusters from growing while undetected. The fact that in the Netherlands there will be ongoing within-country transmission when measures start to be relaxed brings additional complications and challenges to monitoring and TTI-response. In addition, given the fact that the Netherlands is an important nation for tourism, trade, collaboration and industry, there is very substantial interaction between our country and all citizens of nations around the globe. This is likely to resume (slowly) when 'normal' international travel and mobility is restored. As the Covid-19-pandemic is out of phase across the globe, with nations at the beginning of their outbreaks and nations nearing the end of their first waves, it is likely that we will experience importation of cases from abroad, by air, train, boat and car. As the world is currently dealing with a unique new public health problem and threat for the coming years, it is unclear what an effective strategy of monitoring and response is and whether existing protocols and effort are sufficient to prevent new major outbreaks in the Netherlands until a suitable vaccine becomes available. The aim of the project is to provide a broad scientific basis for an effective evidence-based system, including uncertainties, of monitoring and TTI response for SARS-CoV-2 that takes into account the characteristics of Covid-19 disease, the status of the outbreak, potential importation of cases, specific risk and core groups, the impact of basic transmission-avoiding measures and human behaviour. This can only be achieved by bringing together a large group of experts from a wide range of quantitative disciplines and medical/public health institutions and organizations and in coordinated concentrated interaction. The scientific results of the project can be used as input for the RIVM/Cib, GGD, NIVEL and other parties within whose remit it lies to give policy advice on monitoring and control and to implement suitable public health measures in response to Covid-19. On top of that, the methods and models developed during the project will be useful for future outbreaks of newly emerging (respiratory) infections.",2021,2021,Utrecht University,558100,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies,Disease transmission dynamics,2020 +C13748,1.043E+13,Use of primary care during the corona pandemic: a national population study from the perspective of the patient and the healthcare provider,"BACKGROUND During the COVID-19 pandemic, the number of patients that were admitted to hospitals for non-COVID conditions dropped substantially. From March to July 2020, national protection regulations restricted movement among all Dutch citizens, which may have influenced health care seeking behavior. Of particular concern are potential 'side-effects' related to COVID-19, such as delay or failure to seek medical attention in primary care. When left unheeded, such demand for care can result in deleterious health consequences for individuals. This project will quantify changes in healthcare utilization in primary care during the pandemic. It will additionally identify risk groups for targeted education, and will finally determine causes that explain observed changes in healthcare utilization from a patient's perspective. RESEARCH QUESTIONS 1. What are the national and regional consequences of COVID-19 on the use of (regular) primary care during the COVID-19 outbreak, compared to the monitoring period one month or year before the outbreak? 2. What are actual reasons for care avoidance from the perspective of the patient and primary care provider? URGENCE Since the COVID-19 outbreak, people have started shunning care. In addition, the care capacity in general practice is still far from the old level. Decreases in the use of (regular) primary care can lead to additional complications due to, for example, late-diagnosed or untreated heart and vascular diseases or oncological conditions. Although the first peak is behind us, the impact of COVID-19 on healthcare capacity will remain significant due to measures taken and virus flares. It is critical to monitor the change in health care demand and use and identify reasons for changes in healthcare utilization in order to minimize avoidable harm to public health. HYPOTHESIS This study provides insight into the changing use of primary care during the COVID-19 outbreak. It exposes which care needs are being postponed, it identifies groups at risk for targeted public education and identifies the underlying reasons for care avoidance. PLAN OF APPROACH For this mixed-methods study, we make use of seven existing population studies: 6 regional GP registry databases (total: 1,390,000 patients, from 326 general practices), and within ERGO we repeatedly measure the degree and reasons of care avoidance from the perspective of patients (n = 8,732) and caregivers. This unique combination of data from both general practitioners (GP registrations) and patients (ERGO) provides detailed and real-time insight into the consequences of COVID-19 on primary care. Within this national study, we will perform prospective data extractions in order to continue to monitor changes in healthcare use. Keywords / Keywords general practitioner, primary care, prevention, care avoidance, care use, patient, citizen, COVID-19, population research, complications, cardiovascular disease, oncology, incidence, avoidable harm, public health, epidemiology",2021,2022,Erasmus MC,554400.24,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C13749,1.043E+13,A (care) ethical analysis of COVID-19 policymaking,"The measures that the Dutch government took in the first half of 2020 to curb the COVID-19 pandemic successfully slowed down the rate of contaminations and hospitalisations. However, the social and economic costs were high. From an ethical perspective, it is problematic that the far-reaching governmental decisions during those months often lacked a sound ethical argument, or were only accompanied with one-sided utilitarian justifications. This is also troublesome, since the measures especially impacted groups that already found themselves at the margins of public and political attention before the crisis started. Their voices and experiences were not, or barely, included in processes of decision making. At the same time, in the context of stories about exhausted hospital workers and the devastating impact of lockdown measures on vulnerable groups, there was a growing public awareness that care and being cared for are crucial for human flourishing and sustaining a just society. The importance of care and voice, especially for people in the margins, has long been emphasised by care ethicists like Tronto, Sevenhuysen, and Robinson. Therefore, their work seems to be a helpful lens to look back at, and evaluate, the COVID-19 crisis response in order to learn lessons for the future. This project aims to do exactly that, by analysing the drastic policy decisions of the first months from a care ethical perspective, as well as by mapping their impact on vulnerable groups through empirical research. Combined with the reflections of policy makers, these are the building blocks for a new framework for policy making that is ethically coherent and that contributes to a caring democracy, which is resilient enough to respond to future crises in a more inclusive way. This research project consists of four elements. The first is an analysis of the Dutch governmental COVID-19 policies and how these were translated into protocols and measures in the care sector. The focus will be especially on the underlying ethical assumptions and arguments. The second element is a qualitative study that consists of semi-structured interviews and focus groups with people in a vulnerable position, their relatives, professional care workers, and managers. To cover a wide range of care arrangements, four groups will be included: People receiving palliative care, people with mental illness receiving residential care, the elderly living at home who are dependent on informal care, and refugees who have no stable residency. On the one hand, the aim of the empirical research is to understand how the crisis measures impacted the already vulnerable position, the experienced quality of life, and possibilities for hearing the voices of the different groups. On the other hand, the study seeks to explore what creative solutions people found to cope with the impact of the pandemic and the emergency policies. The third element of this project is the drafting of a policy framework based on a care ethical reflection that combines the findings of the policy analysis and the empirical research. This framework will be developed together with policy makers and discussed during round tables with Dutch and international (care) ethicists, as well as policy makers from several sectors, especially education and culture. After these consultations, the framework will be finalised. The fourth element is dissemination: the framework will be presented during a conference with relevant national policymakers. Smaller events will be organised with and for the four vulnerable groups that are at the centre of this project. Through online and offline publications of the policy framework, academic papers, and the network resulting from this project, the dissemination of the lessons learned will be ensured.",2021,2022,Universiteit voor Humanistiek,223444.24,Unspecified,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Governance | Policy research and interventions,2020 +C13750,1.043E+13,Mobility- and behavior-based early-warning system after the first wave of COVID-19,"This project aims to develop a mobility- and behavior-based early-warning system after the first wave of COVID-19 in the Netherlands. In the current phase of the outbreak in Europe, local lockdowns have become part of the containment policies in several countries, including Spain and Germany and are discussed in the Netherlands (RTL Nieuws, 14-07-2020). We will investigate whether, how and under what conditions these measures could be effective and feasible. - We use the information on syndrome and behavior surveillance and mobility, already available to us. - We enable regional decision-making by creating decision support tools in the form of dashboards, complementary to those by the Ministry of Health, and investigate the policy response. - While testing implies inevitable delays, our approach enables quick action because we can observe high-risk behavior almost instantaneously, and we predict the progression of the disease spread. HYPOTHESIS Information on mobility with real-time information on symptoms and risky behavior, combined in a mathematical model, can enable an effective regional early-warning system and decision support tools for policy response in containment of COVID-19 after the first wave. The consortium has expertise in mathematical models for spreading processes (TU/e), epidemiology (UU, LUMC), behavioral sciences (LUMC), data analytics (Mezuro, Ilionx),and governance (UT). We use the mobility information available at Mezuro and the syndrome and behaviour surveillance data from the COVID Radar app by the LUMC. The project consists of three work packages (WPs): WP 1 optimizes the COVID Radar app and integrates its data with the Mezuro mobility data. WP2 develops mathematical epidemiological models that quantify and predict the spread of Covid-19 in the Netherlands. WP 3 delivers an early-warning decision support system in the form of dashboards and investigates the policy response.",2021,2022,Technische Universiteit Eindhoven,528035.47,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C13751,1.043E+13,Ethics of e-Health during the corona crisis and afterwards: lessons from the pandemic,"Due to the Covid-19 pandemic, prevention and (long-term) care must now often be provided remotely: image care, apps for self-monitoring and detecting infections, virtual visits, etc. Care consultations (MDO) also took place virtually. What is new is that e-health replaced direct interaction and was not just a supplement. We want from this 'natural' experiment"" learn how this technology can be used in an ethical and legally responsible manner during and after the corona crisis, building on previous work on 'remote care' and linking up with ongoing projects. Research questions: - Which moral/legal problems and opportunities did/are encountered when using e-health in primary, secondary & secondary healthcare, GGZ and long-term care for (non-)COVID patients during the corona crisis? - How can we learn from this when developing and adapting e-health in different care practices for the (near) future? Urgency: In the 1,5 meter society, direct contact is still very limited, while the demand for care during this period is still very limited protracted crisis is likely to continue to intensify. The development and improvement of e-health is therefore more urgent than ever. It is therefore all the more important that e-health applications are used that are medically ethical and legally responsible. Hypotheses: Experiences with e-health applications during the Covid-19 pandemic offer new practical insights and concrete guidelines for improving and developing ethically and legally responsible care. Plan of approach: 1. qualitative research ((group) interviews/observations/expert meetings), both retro- and prospective, into the experiences of healthcare providers, patients and family, developers on the basis of 8 cases in the above-mentioned care domains; 2. ethical and technological-philosophical analysis of the empirical findings; 3. legal analysis of identified bottlenecks; 4. proposals for responsible integration of e-health in remote care.",2021,2022,Erasmus MC,256914.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Research to inform ethical issues | Health Systems Research,Health service delivery,2020 +C13752,1.043E+13,The impact of the corona crisis on the Dutch judiciary and the position of vulnerable litigants,"As a result of the COVID-19 measures, many lawsuits have been cancelled. Despite this crisis, the Dutch judiciary has attempted to handle the most urgent cases, usually by organising digital hearings or by hearing litigants from a distance. This has led to considerable innovations in digital communication in particular, from which lessons may be learnt for the future. A complete picture of all the measures that have been taken and of their impact on the judiciary and on especially vulnerable litigants is not yet available however. This research project, which is jointly conducted by Utrecht University, Leiden University and the Radboud University, will map out the problems with which the judiciary has been confronted during the corona crisis (until 15 September 2020), which measures the judiciary has taken and which effect the problems and measures have had on the fundamental rights of vulnerable litigants in particular and on their trust in the judiciary. To this end, interviews will be conducted with judges and other relevant authorities and surveys will be distributed among litigants who had contact with the judiciary during the corona crisis. The research project focuses on the following three areas of domestic law: criminal law, immigration law and civil juvenile law. This selection has been made because cases have been handled in these areas of law during even during the beginning of the crisis and because the vulnerability of involved litigants is considerable. The empirical research findings will be evaluated in the light of fundamental rights and theories of procedural justice. This evaluation will give insight into whether the measures should be kept in place during this crisis and once the corona crisis has ended. In this way, the research project aims to contribute to further developing the institution of the judiciary as such in the Netherlands and to strengthening respect for fundamental rights during and outside times of crisis.",2021,2021,Radboud Universiteit Nijmegen,389734.59,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C13753,1.043E+13,The impact of social distancing on the psychosocial well-being of visually impaired and deafblind persons: A human-centered design leading to effective solutions,"About 300.000 persons in the Netherlands who suffer from a visual impairment or deafblindness experience severe consequences of the social distancing guidelines introduced to control the COVID-19 virus. Social distancing leads to limitations in daily activities for these target groups, such as entering public spaces and shops, using public transport, and receiving physical help from others with navigation and communication. These limitations lead to stress, anxiety, feelings of loneliness and loss of autonomy. Thereafter, this has a great impact on their psychosocial wellbeing. A panel of experience experts, representative for the target groups, will be actively involved in developing effective solutions for increasing the psychosocial wellbeing in a social distancing society. By conducting participatory research according to Human-Centered Design, including (group) interviews, observations, co-creation sessions and diaries to record personal experiences, several prototypes will be developed and tested. The two of three most successful prototypes will be developed into more elaborated prototypes that are developed further for implementation. The consortium consists of experts on developing (digital) innovations with the target group (Saxion, NHL Stenden and Windesheim), the patient association for persons with visual impairment and deafblindness (Oogvereniging) and expertise centers for visually impaired persons (Bartiméus, Royal Dutch Visio and Robert Coppes Foundation). In close collaboration with the target groups the project will result in two to three working and effective prototypes in the short, but feasible time of one year. Keywords: Social distancing, Visual impairment, Deafblindness, Psychosocial well-being, Experience expertise, Human-Centered-Design",2021,2021,Saxion,128678.67,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C13754,1.043E+13,"Preconditions for Covid-19 mobile apps: A feature-level investigation of user acceptance based on insights from South Korea and Canada, applied in the Netherlands","RESEARCH QUESTION: How does the Dutch public perceive the privacy and efficacy of potential technologies used for managing Covid-19? How can culturally embedded views on privacy and transparency from other countries be leveraged to enable a secure and efficient app in the Netherlands? How do experts consider the results of the survey in regards to implementation in the app? URGENCY: The Dutch government has installed a task force working on understanding technical requirements and citizen attitudes regarding Covid-19 apps. Tracking is important to prevent or manage a second wave of infections. This project aims to contribute detailed insights in just over 4 months. HYPOTHESIS: Our study will reveal preferences and opinions about the adoption of apps in the Netherlands. Evidence suggests that citizens in South Korea are more accepting of actions taken to promote public health and more open to surveillance, which has allowed for the rapid implementation of mobile apps. We expect their existing technologies, as well as experiences from Canada, to be useful in providing the basis for our survey and for discussing how to explain and market a Covid-19 app in the Netherlands. ACTION PLAN: The project has three work packages (WPs): 1) Design a feature-specific survey and administer it with a representative sample of the Dutch public. 2) Gather expert feedback on survey results and implications for implementation by means of an expert Delphi discussion. Experts will include policymakers, software developers, privacy and legal experts and healthcare workers. 3) Host interactive expert session to discuss results of WPs 1&2. Summarize results and provide recommendations based on the first two work packages into final report. Share images and clips of data on social media with a link to the final report.",2021,2020,Tilburg University,49363.38,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C13755,1.043E+13,EXCEPTIUS Exceptional powers in time of Sars-CoV-2 crisis,"RESEARCH QUESTIONS 1)What are the political impacts of exceptional decision making in European countries? 2)What are the determinants of cross-national variation in exceptionalism? URGENCY Although initially strong (especially in the Netherlands) public support for emergency measures has progressively eroded as the severity of the pandemic has lessened. Throughout Europe, citizens are increasingly critical about the democratic costs of the management of the pandemic. Moreover, exceptional measures can durably affect democratic equilibria. If unaddressed, this decrease in public trust can reduce citizens compliance with public health measures and destabilize democratic stability. This calls for urgent research on the modalities, impacts and rationale of emergency decisions in pandemic times and other exogenous shocks. HYPOTHESES Based on theories of emergency decision-making, we hypothesize that exceptionalism (measured by its severity and its design) is influenced by 8 factors: people's compliance, democratic legitimacy,democratic stability, the severity of the pandemic, contagion over Europe, legal preparedness, equilibrium of counter-powers and national democratic culture. In turn, exceptionalism negatively affects democratic resilience (political legitimacy + regime stability), but increases people's compliance and reduces the severity of the pandemic. ACTION PLAN EXCEPTIUS is a 2 years European transdisciplinary project, led by the University of Groningen supported by a Board and based on a three-staged approach. First, metrics of exceptionalism in all EEA countries will be defined and made publicly available in an open-access dashboard. Second, the health and political impacts of exceptional measures will be assessed through synthetic control analyses. Third, the determinants of cross-national variation will be analyzed based the severity of the crisis and domestic and international political constraints using pooled time-series regression analyses.",2021,2022,Rijksuniversiteit Groningen,221567.01,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C13756,1.043E+13,Against the background of government measures - decision-making and moral leadership of healthcare executives,"The Corona era is a special time, also for healthcare executives. They are faced with complex issues that require fast and adequate decision-making, in an arena full of uncertainty and diverse stakeholders. As we enter the post-acute phase of the crisis, a pressing question for the future is what we can learn from this crisis. Therefore, the central question of this project is: ""What do the experiences of healthcare executives during the corona crisis teach us about good governance, especially in times of crisis? How can these insights about good governance be used for the further professionalization of healthcare executives and used by healthcare executives, government and other stakeholders in preparation for future crises and issues? "" During the acute phase of the corona crisis there was a lack of knowledge, information and resources. The course of the crisis was by no means predictable. Well-known authors in the field of leadership and crisis management propose - given the specific nature of this crisis - an adaptive leadership style (Macpherson & 't Hart 2020): iterative and tailor-made intervention, evaluation and learning (see also Heifetz et al. 2017). Learning focuses on dealing with the daily issues that arise during crises. Also, ethicists in the media called for more reflection on the ethical issues raised by the crisis (including Baart 2020, De Lange 2020). Macpherson & 't Hart also make a plea for another, more in-depth, form of learning: ""They need to personally undertake critical reflective and diagnostic work"". It is precisely this critical and reflective practice that is the object of this research. Research into the reflective and normative practice of healthcare management in times of crisis requires descriptive research. It also requires an interpretive approach, in which the knowledge that is inherent in the actions of healthcare executives - the knowledge in action (Hajer & Cook 2003) - is unlocked, so that it can be strategically deployed and is questionable and transferable. Reflective knowledge is the knowledge that arises through reflection on the events that happen to people and is focused on their own way of dealing with them (Schön 1983). Such reflection turns people into knowledgeable agents, capable of understanding and give meaning to the drastic events of this time (Giddens 1984; Sewell 1992; Leca and Naccache 2006; Cooney 2007). Sharing the deep, internalized knowledge made available in this way with peers (peer group learning) helps to build a strong community of practice of knowledgeable agents (Van der Scheer 2013). Sharing and questioning this knowledge with and by other relevant agents (professionals, supervisors, patients) contributes to a learning process at the level of the sector as a whole (sector learning). The study has a qualitative interpretative research design. First, data is collected through 31 semi-structured interviews with healthcare executives and experts, from all sub-sectors in health care (e.g. hospitals, nursing homes, mental healthcare). Second, insights from the interviews are deepened with focus groups of healthcare executives. Third, enrichment sessions are organized with a broad group of stakeholders (professionals, institutions, experts, patients) to reflect on the findings of the interviews and focus groups. The results of the three research phases are described in a concise research report, which will be widely shared with the professional field, to promote the practice of governance in the form of 'actionable knowledge.",2021,2021,Erasmus University Rotterdam,66418.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,Health Systems Research,Health leadership and governance,2020 +C13757,1.043E+13,Migrants at the front lines. The effects of COVID-19 measures on migrant workers working in crucial sectors,"Migrant workers were performing crucial work in the front line of the COVID-19 crisis. They help produce our food, pack our orders, clean our houses. The protection of these migrant workers requires urgent attention. An team of interdisciplinary researchers at the Radboud University Network on Migrant Inclusion (RUNOMI), together with De Burcht and partners from the field will investigate which structural problems related to labor migration have been exposed by the corona crisis. Also, the opportunities for improving the protection of migrant workers will be investigated. We will look for innovations that make crucial sectors less dependent on vulnerable migrants. Because migrant workers often work and live across borders, this research focuses on the border regions (Netherlands/North Rhine-Westphalia). The research aims to contribute to reducing health risks during the further course of this, and possible future, crises.",2021,2022,Radboud Universiteit Nijmegen,558682.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Europe,,,,Netherlands,Netherlands,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Economic impacts,2020 +C13758,1.043E+13,"COVID-19, Food Security and Economic Diversity in Curaçao, Aruba and Sint Maarten","The socio-economic impact of the COVID-19 pandemic upon the island states of Curaçao, Aruba and Sint Maarten has exacerbated the need for both economic diversification and the bolstering of food security. This research project seeks to explore how the pandemic has affected local food systems and how sustainable agricultural production can contribute to diversification strategies that will help make the islands pandemic resilient. Central to this project is the participation of local stakeholders and community members in the design of data collection and interpretation. Work Package (WP)1 measures the impact of COVID-19 on the sustainability of food systems and community responses to food security since the outbreak of the COVID-19 pandemic. WP 2 explores sustainable economic diversification strategies and food production systems. Together, these will provide important baseline data that can be used to inform evidence-based policy aimed at: 1. increasing local sustainable agricultural development; 2. increasing food and nutrition security; 3. developing innovative small and medium business enterprises supporting agricultural development; 4. building regional consortiums; and 5. promoting economic diversity. The research consortium consists of a research team on all three islands with institutional support from the University of St. Martin, the University of Curaçao Research Institute (UCRI) and the University of Aruba Sustainable Island Solutions through Science, Technology, Engineering and Mathematics (SISSTEM).",2021,2023,University of St. Martin,284562.38,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Americas,Americas,,,,Saint Martin (French part),Aruba,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +C13759,177693,Viral diversity and immune escape variants in vulnerable individuals post-vaccination.,"Emerging viral variants are burgeoning rapidly in this COVID-19 pandemic. However, a number of critical questions remain unanswered and require a rapid response to influence public health decisions, to prevent subsequent pandemic waves, and to reduce their impacts. Are all variants of public health concern? Which variants acquire the capability to evade vaccine-induced protection and re-infect vaccinated individuals? Does the age or the immune status of the individual influence the evolution and transmission of variants, particularly vaccination? To address these essential and urgent questions, our multi-disciplinary team of researchers will actively investigate new infections in previously vaccinated individuals in the general population, as well as among defined cohorts of patients of elderly and cancer patients. We will intently probe for the emergence of novel SARS-CoV-2 variants in these post-vaccination populations and assess their impact on human health through viral genomics, computational biology, and immune testing. Our proposal rests on 3 major thematic pillars: A.Clinical surveillance of SARS-CoV-2 variants in human cohorts. We are exploiting novel sequencing technologies for rapid variant detection through viral genomics in defined human cohorts. B.Viral genome analysis. We will sequence viral genome from this cohort and track mutations both within and between patients. We will put these genomes in the phylogenetic context of global and pan-Canadian genome databases to infer transmission events of variants into and out of elderly and immunocompromised individuals. C.Immunological and functional evaluation of SARS-CoV-2 variants. Modelling of mutated viral proteins will predict their impact on epitope diversity/antigenicity, cellular and humoral immunity, and serological detection. We will model the future transmission of SARS-CoV-2 to identify optimal control scenarios where the effectiveness of available vaccines is reduced.",2021,2022,Research Institute of the McGill University Health Centre/Institut de recherche du Centre universitaire de santé McGill,398601,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Disease pathogenesis",2021 +C13760,177694,Pathogenesis and immune escape potential of SARS-CoV-2 variants of concern.,"The biology of RNA viruses, including SARS-CoV-2, is such that mutations constantly arise upon viral replication. The appearance of variants is therefore expected. The more selective pressure is put on the virus, the more frequent mutations are likely to arise. Fortunately, the majority of these mutations will be silent (synonymous mutations) or even harmful and therefore will not provide a growth advantage to the virus and will not be selected for. However, as we have recently experienced with the current pandemic, some mutations confer new properties that allow these variants to have a growth advantage over the original virus. These variants can spread rapidly and become the dominant strains infecting the population. This was experienced first-hand in the current pandemic with several variants, such as B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil), becoming the most common circulating viruses across various geographical areas. All current vaccine efforts are designed based on the original SARS-CoV-2 Wuhan strain. Whether vaccine induced protection is efficacious against variants of concern (VOC) is only partly known. In fact, in vitro results indicate that neutralization of the B.1.351 is much reduced. Similarly, whether these VOC are more or less pathogenic remains to be studied in detail. In the current proposal, we will compare the disease caused by VOC in young and old mice of both sexes. We will also explore potential therapeutic avenues by studying the roles of serotonin and thromboxane flowing infection of mice with the virus. Lastly, we will study the evolution of VOC and determine whether these evolved VOC are more pathogenic and whether they can infect mice that have received the current vaccines.",2021,2022,CHU de Québec,201814.2,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +C13761,177695,Development of a rapid and simple test to detect the COVID-19 variants that can be used in remote areas and developing countries.,"We have developed a rapid and simple test to detect COVID-19. It uses RNA extracted from a gargle sample. If present, millions of copies of a part of the SARS-Cov-2 are amplified at a fix temperature. Thus the test does not require an expensive temperature cycler normally used for RT-qPCR. The amplified SARS-CoV-2 RNA fragments are specifically cut by the Cas13a RNAse and a crRNA that detects a sequence of 28 nucleotides. Following this specific cut, the Cas13a cuts all the other RNAs present in the sample including a reporter RNA containing a fluorescein molecule on one end and a quencher on the other. When the reporter is intact and the fluorescein molecule is close to the quencher, the latter absorbs the fluorescent signal and the sample stays dark. However, following the cut of the reporter RNA by Cas13a, the positive samples become fluorescent green under a UV light. The proposed project objective is to modify our current test to detect and differentiate between the SARS-CoV-2 variants (London, South African and Brazilian variants) rapidly (under 2 hours) in remote regions of Canada and in developing countries. The modified test will use two enzymes simultaneously: Cas13, which cuts the RNA including a fluorescent green reporter RNA, and Cas12, which cuts DNA including a fluorescent yellow reporter DNA. The cutting of that reporter DNA leads to fluorescence at a different wavelength. The presence of one the fluorescence signals in two wells will serve to identify which variant is present in the sample. These fluorescent signals will be detected with a smartphone camera and the color combinations will be analyzed in large quantities by a cloud-based server to determine which variants are present and create anonymized reports. For this project, we have thus established collaborations with clinicians in several countries (Brazil, Maroc, Central African Republic, and Congo). In the future, the test will be modified to detect other viral and bacterial infections.",2021,2022,Université Laval,158901.75,Viruses,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C13762,177696,Errant epitopes from arginine methylated SARS-CoV-2 proteins predisposing to autoimmune diseases.,"Drugs that can inhibit SARS-CoV-2 replication are urgently needed besides vaccines. The drugs can target the variants while vaccines provide limited immunity against only 1 protein, namely Spike. Our data show that viral proteins are modified post-translationally on arginine (methyl arginines) by protein arginine methyltransferases. This modification is necessary for the virus to suppress the anti-viral response and allow viral replication. We have shown that the N protein is arginine methylated and this is necessary for its function. Actually it is known that we develop antibodies against N protein, as it is very immunogenic. In addition, there are mutations in a key arginine residue in B.1.17 variant. In this proposal, we aim to understand how the methylated viral proteins are recognized by the immune system and if we will develop in the future autoimmune diseases because of this.",2021,2022,Lady Davis Institute for Medical Research,246781.5,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C13763,177697,Teasing apart the differential impact of variants of concern on COVID-19 severity and health inequities: a population-based genomic epidemiological investigation in Ontario and British Columbia.,"As the COVID-19 pandemic turns the one year mark, the causative agent of this disease, SARS-CoV-2 is presenting the Canadian population with new challenges: variants of concern (VoCs), which are mutated strains with undesirable characteristics such as enhanced ability to transmit. VoCs threaten the public health gains obtained via various control measures and may even boost a new trajectory for the pandemic and worsen health inequities. There is early evidence suggesting that these variants may also have deleterious clinical impacts by increasing the disease severity, but these studies used surveillance data alone, and were challenged by potential biases such as the inability to account for factors like chronic health conditions that could act as confounders, and different time periods of comparison - most studies compared severity from VoCs now with cases from a few months ago. Therefore there is urgency in fully understanding the extent of their virulence with population based approaches that can limit these biases. To this end, we propose to use genomic and population-level clinical data on all cases of COVID-19 in two provinces where VoCs were first detected, British Columbia and Ontario, and to fully investigate each of the circulating variant, namely B.1.1.7, B.1.351 and P.1; as well as the role of specific mutations with severity, such as time to clinical deterioration, hospitalizations, need for intensive care, and mortality. We will then estimate the extent to which VoCs may amplify inequities in health outcomes among the most affected communities, such as those living in congregate settings, essential workers, and multigenerational and dense households. The goal of this collaboration is to leverage extensive scientific and methodological expertise, large population-level data and laboratory diagnostic tests, and thousands of genomic sequences to support efficient and proactive public health and health system response to this ever evolving pathogen.",2021,2022,B.C. Centre for Disease Control,360048.02,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease susceptibility",2021 +C13764,177698,Variations on a theme: New approaches to examine SARS-CoV-2 variants and their ABO connections,"Many studies have reported an association between ABO blood group and COVID-19. People who are blood group A tend to have a higher infection rate and a worse course of disease than people who are blood group O. However, for the SARS-CoV-2 virus variants (UK, South Africa, Brazil), the association of ABO blood group and COVID-19 remains unclear. Here, we propose to explore reasons behind this association and whether these are the same for the variant viruses. One reason for the association of COVID-19 with blood group could relate to the 'sugars' that make up the ABO blood group. We have different ABO sugars in our bodies depending on our blood group (either A, B, AB or O). In A, B or AB people these sugars are on cells in the nasal passages and lung and may be used by the virus to enter our bodies and infect these cells. Another reason that ABO blood group may influence COVID-19 is through ABO antibodies that are produced 'naturally' in people depending on their blood group. (We produce ABO antibodies to the ABO sugars that we do not have. For instance, ABO-O people make antibodies to A and B sugars vs ABO-A people make antibodies only to B sugars). ABO antibodies could protect from infection by binding to the virus making it harder to infect cells. Both of these possibilities may be important and may happen together. Working with scientists and clinicians around the world, we will use special tools to: (1) study the binding of the SARS-CoV-2 virus (and variants) to ABO blood group sugars, and (2) measure ABO antibodies in the blood of COVID-19 patients (with known variant infection) and their binding to the virus. If we can understand how ABO blood group affects COVID infections, it may be possible to help guide better clinical treatment or preventative strategies. For instance, an understanding of the connection between ABO and COVID-19 could lead to new treatments for COVID-19 by blocking ABO sugars or by stimulating more ABO antibodies.",2021,2022,University of Alberta,385382.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C13765,177699,Risk of Environmental Surface and Air Contamination in COVID-19 Caused by Variant Viruses (RISC-COV-Variants),"COVID-19 is an infection caused by a virus called SARS-CoV-2. The original form of this virus first emerged in late 2019 and has caused a worldwide pandemic. This virus is transmitted from person to person, usually before or at the beginning of infection, predominantly via large respiratory droplets, although airborne smaller particles, and the contaminated environment may play a role. The best test to detect infection is with a swab of the back of the nose called a nasopharyngeal swab. Like influenza, this coronavirus changes over time. In influenza, changes in the virus mean that the virus evades immunity, so that previously infected and vaccinated people becoming re-infected. This is likely to occur with SARS-CoV-2 as well. However, the situation with coronaviruses is worse than with influenza: coronaviruses are known for their ability to change many different characteristics. Thus, although we are worried that changes may make vaccine less effective, it is also true that the virus might change how or when it is transmitted, or what the best test for detection is. Our study will take advantage of previous work with COVID-19 by our group, and a network of researchers called the Toronto Invasive Bacterial Diseases Network (www.tibdn.ca) to ask whether or not new variants of COVID have different characteristics than the original virus. For a serious of variants of SARS-CoV-2, we will study whether the air and environment around COVID-19 patients is contaminated with virus, what the best diagnostic test for COVID-19 is, and how long people test positive during their illnesses.",2021,2022,Sinai Health System,398177.26,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations | Environmental stability of pathogen",2021 +C13766,177700,Peginterferon lambda to treat outpatients with COVID-19 to prevent severe disease: Focus on variants of concern,"The COVID-19 pandemic continues to cause major problems globally. The appearance of multiple variants of concern (VOC) that spread more easily and cause more severe disease has led to surges of infection in Canada and abroad. There is concern that new variants may evade vaccine responses. The numbers of VOC have risen dramatically. In Toronto, VOC have increased from ~10% to >80% of all newly diagnosed cases of COVID-19 in just 2 months with devastating effects on hospitalization, need for ICU care and mortality. To address the spread and health consequences of VOC, antiviral therapies unaffected by the sequence of the virus are urgently needed. Interferons are hormones that the body produces to fight off viral infections. They are the body's first defense against most viral infections, so their activity does not depend on the sequence of the virus. We have previously shown that peginterferon lambda, a Type III interferon, with fewer side effects than other interferons, is very active against COVID-19. In our previous trial, treatment sped up clearance of the virus. We now propose to do a larger study with 610 people to see if peginterferon-lambda is effective against VOC and if it will prevent outpatients from requiring hospitalization. People with COVID-19 with risk factors for severe disease will be randomized to get a single shot of peginterferon lambda under the skin or a matching placebo and we will assess whether treatment reduces the risk of hospitalization and leads to clearance of the virus more quickly than placebo. We will enroll 200 people in Toronto and will partner with a large group in Brazil where VOC are a major problem. The Brazilian team will enroll 410 people allowing us to evaluate treatment in 610 people to determine if peginterferon lambda is effective. We will also study in the lab how this treatment activates specialized immune cells to fight the virus with a particular focus on how it works against VOC.",2021,2022,University Health Network,793547.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | Brazil,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2021 +C13767,177701,"SARS-CoV-2 variants under investigation (VUIs) and variants of concern (VOCs); phenotyping gaps in transmission, reinfection and response to medical countermeasures","Over the course of this pandemic, we have been monitoring how the SARS-CoV-2 virus has been changing using whole genome sequencing. We now know that many Canadians are infected with variants of concern (VOCs). These are viruses bearing mutations which change how the virus causes disease, transmits or responds to antivirals and vaccines. We have also identified several viruses that harbour suspicious mutations that require further investigation (variants under investigation or VUIs) to determine whether they are VOCs or not. Our group has sequenced over two thousand SARS-CoV-2 viruses from patients, and made these data publicly available to enable others to address a broad range of research gaps. Many of these data are used for general surveillance, but segments of the population do not benefit equally from these technological advances. In March of 2020 we isolated the SARS-CoV-2 virus in a high containment laboratory, and since then we have cultured hundreds of viruses including VOCs and VUIs. We have also established experimental models for SARS-CoV infection and transmission to answer critical questions as they relate to viral disease and spread. We have already done this with a variant called D614G which established itself in Canada early in the pandemic. We propose to use both our virobank and the models we have established to characterize emerging VOCs and VUIs to identify viral determinants of transmission, reinfection and disease, including at risk populations with a focus on the corrections system. Our group moves seamlessly from bedside to bench and back, translating research starting with patient material to generate viral genomes and isolates which we then study in cell and animal models in high containment. This work stands to impact patient care and public health; the pandemic is sustained through person-to-person transmission, and as vaccines and therapeutics are put into broad use, we need to ensure that these interventions remain effective.",2021,2022,Sunnybrook Research Institute,398422.25,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2021 +C13768,177702,Determine how the interaction between SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2) affect viral spread and the severity of COVID-19 outcomes.,"The proposed research focuses on investigating why the SARS-CoV-2 variant, B.1.1.7 that have higher binding affinity to Angiotensin Converting Enzyme 2 (ACE2) on host cells are associated with increased viral spread and mortality rates. ACE2, the main receptor for HCoV-NL63 (common cold virus), SARS-CoV-1 and SARS-CoV-2, is also a key regulator of the renin-angiotensin system (RAS) regulating systemic vascular resistance, which is enhanced in COVID-19 patients with severe disease outcomes. While most studies continue to focus on ACE2's role in RAS, its role in immune modulation and the signal transduction property of its intracellular subdomains have been overlooked. Viral spread is associated with reduced immune response in controlling viral infection and replication and COVID-19 severity is associated with exaggerated inflammation causing damages of critical tissues. ACE2's contribution in preventing inflammation is evident from study of SARS-CoV-1 infection and reduced surface ACE2 expression that is associated with the severity of SARS-CoV-2 infection. Moreover, unlike SARS-CoV-1 and -2, HCoV-NL63 (common cold virus) did not trigger ACE2 shedding. It remains unclear, to what extend SARS-CoV-2-triggered ACE2-shedding affects the inflammation observed in coronavirus infection and viral replication in infected cells. The observation that B.1.1.7, exhibiting enhanced binding affinity for ACE2 caused exacerbated transmissibility and mortality without affecting disease severity further emphasized the urgency to define how SARS-CoV-2 and its VoC modulate the immune activation and cell signalling mediated by ACE2. This knowledge is especially critical for better patient-management and when targeting ACE2 as prophylactic therapeutic strategies to halt the disease progression towards excessive inflammation and acute respiratory distress syndrome during SARS-CoV-2 infection.",2021,2022,University of Manitoba,343938,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C13769,177703,Variants of concern: escape from infection- and vaccination-induced immunity in older adults,"One year after the beginning of the COVID-19 pandemic, much has been learned on the biology of the virus that causes it, SARS-CoV-2. We know that it can enter human cells through the binding of the virus spike protein to a protein at the surface of human cells called ACE2. In response to viral infection, the body tries to defend itself by producing antibodies, including a class of antibodies that attach to the virus spike protein and prevent it from binding to the ACE2 protein on human cells (we call these ""neutralizing antibodies""). The vaccines approved in Canada work by mimicking the viral spike protein, inducing the production of neutralizing antibodies. While the vaccines have been extremely successful to drive immunity to the originally circulating strain, RNA viruses like SARS-CoV-2 make mistakes when they replicate their genetic material; these mistakes are called ""mutations"". Often, the mutations do not change the virus properties, or negatively affect the virus, but sometimes, the mutations offer the virus some selective advantages. Some of the mutations have caused spike to bind more tightly to ACE2 - this is the case of the B.1.1.17 strain first identified in the UK, while some of the mutations make the virus less efficiently ""neutralized"" by antibodies. These viruses that have mutations that potentially render them more dangerous are called ""Variants of Concern"", or VOCs, and we expect that new such variants will continue to emerge. Here, we want to study to what extent the different variants that are circulating in Canada are efficiently ""neutralized"" by the immune system of older adults, because this population is likely to build lower levels of antibodies following vaccination and is more susceptible to severe disease.",2021,2022,Sinai Health System,395934.88,Human Populations | Viruses,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +C13770,177704,Intravital imaging of COVID-19 lungs to visualize pathogenic differences between SARS-CoV-2 variants of concern,"One of the most enigmatic features of SARS-CoV-2 infection is the clinical observation that some individuals have a mild infection that does not require any medical treatment, while others develop severe Coronavirus Disease (COVID) that results in hospitalization and even death. Doctors and scientists are guessing at what causes severe COVID. We propose to look inside the body to elucidate this issue. Our team is comprised of Dr. Corcoran, uniquely an endothelial cell virologist, Dr Braedon McDonald an ICU doctor that takes care of COVID patients and Dr. Kubes, an immunologist and one of the few investigators worldwide capable of visualizing active immune responses after lung infection in living animals. Our combination of expertise will permit us to mutate or fluorescently tag SARS-CoV-2 variants in order to watch the virus as it infects the animal or human blood vessels. It is our believe the lining of blood vessels gets infected. We can color-code each immune cell, visualize blood vessels, and witness the virus-host battle in real time using imaging. We now plan to extend our initial studies on an early isolate of SARS-CoV-2 to the variants of concern. We have a clinical source for patient isolates of SARS-CoV-2 variants, in order to compare how immune responses and disease course including the long haul effects may differ in these infections compared to the 'original' SARS-CoV-2 strain. We will use the SARS-CoV-2 infectious clone that turns cells green after it infects them to track the course of the virus and variants in live animals and human vessels. With these tools and protocols in place, and our functional CL3 facility, our group is poised to make important observations about how the variants of concern may alter the course of infection and the immune response that will complement clinical data. Finally, we have a number of potential therapeutic targets (one of which is in phase 2 clinical trials) to test efficacy in infections with the various variants.",2021,2022,University of Calgary,398863.54,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Immunity | Pathogen morphology, shedding & natural history | Phase 2 clinical trial",2021 +C13771,177705,Mapping the Emergence and Functional Impact of Novel SARS-CoV-2 Variants,"Outbreaks of respiratory viral infections over the past 20 years recently culminated in the COVID-19 pandemic caused by SARS-CoV-2. In a globalized world, repeated cycles of novel viral pathogen is creating an urgent need for population-level molecular screens. SARS-CoV-2 puts this need in sharp relief, as infection leads to generic symptoms of common respiratory pathogens (dry cough, fever and diarrhea), coupled to a broad range of disease manifestations from no/minor symptoms, to acute respiratory distress and death. As the COVID-19 pandemic expanded across the world, the virus started mutating into variants that possess immune evasive properties. They are often referred to as Variants Of Concern (or VOCs). The emergence of SARS-CoV-2 variants can provide viral reservoirs that can be a source of re-infection and reduced efficacy of vaccines. In this proposal we will use data gathered from systematic screening and sequencing of thousands of positive COVID-19 samples identified in a Toronto clinical diagnostics lab since December 2020 to identify known and novel VOCs and define the functional impact of the mutations on the ability of the virus to infect/kill cells and be neutralized by antibodies against the virus. It is well established that VOCs are more infectious and more deadly than the WT SARS-CoV-2 strain, but we do not know why. To address this, our team will use next-generation sequencing methods to profile gene-expression in patients infected with wild-type SARS-CoV-2 or VOCs. This will allow us to determine which genes are up/down regulated in response to VOC infection and illuminate potential treatment options. We will use advanced mathematical modelling to monitor and predict the spread and prevalence of the most concerning VOCs. Early identification of viral variants that escape the immune system would provide an opportunity to intervene and prevent spread of therapy-resistant COVID-19 as well as to instruct public health response.",2021,2022,Sinai Health System,356107.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C13772,177706,The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-acquired Pneumonia (REMAP-CAP): Building an International Research Response to Variant COVID-19,"Information about the best treatments for patients with COVID-19 is being generated at a record pace. Large international clinical trials have been central to this process. REMAP-CAP - the Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia - is one such trial; it focuses on the care of the sickest patients, those who are ill enough to need organ support in an intensive care unit (ICU). REMAP-CAP is currently active in 310 sites on 5 continents. It has recruited more than 6150 COVID-19 patients, and identified three treatments that improve patient outcomes - treatment with corticosteroids, inhibition of a protein called IL-6, and blood thinners in some, but not all patients. As COVID-19 continues in Canada and around the world, new variants have become the most common causes. These are infecting younger patients and resulting in more ICU admissions. REMAP-CAP in Canada has exhausted its initial funding; we seek to maintain our leadership role in the international effort to overcome COVID-19. We will direct our attention to understanding treatments for these new variants in three ways. First, we will focus on treatments that seem to be more effective in patients with severe disease, and in particular, on treatments that interfere with interactions between the virus and a protein called ACE2 that the virus uses to enter cells. Second, we will use international variability in rates of variant disease to determine whether the effectiveness of treatment is influenced by the infecting variant. Finally we will work to expand out network of 34 recruiting sites to ensure that we are enrolling patients from across the country, and in particular where rates of infection are highest. In partnership with clinical researchers around the world, we will collaborate to understand how best to care for the sickest Canadians with COVID-19.",2021,2022,Unity Health Toronto,798000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments | Clinical trial (unspecified trial phase)",2021 +C13773,177707,Comparative analyses of how SARS-CoV-2 variants of concern affect the host response in cells of the respiratory tract,"The COVID-19 pandemic has resulted in the biggest global health crisis in over a century causing ~3 million deaths so far. The causative agent of COVID-19 is a newly emerged coronavirus (SARS-CoV-2) that has continuously evolved into ever more transmissible and pathogenic variants that has exacerbated the spread of the virus across the globe. Due to their high transmissibility and potential resistance to current vaccines, these newly emerging strains of SARS-CoV-2 have been termed 'variants of concern (VOCs)'. The most prominent among these VOCs are the UK strain (B1.1.7), South African strain (B.1.351) and the Brazilian strain (P.1). The number of active COVID-19 cases is again increasing in multiple countries due to the emergence of coronavirus VOCs. These variants contain characteristic genetic mutations in multiple viral genes. While much of the focus has been on mutations in the spike protein gene which can alter binding to host cells and potentially evade vaccine-induced antibodies, it is largely unknown how other mutations in VOCs affect replication and pathogenesis of SARSCoV-2. In this proposal, we will used single cell RNA sequencing to study the interaction of SARSCoV-2 variants with the cells from the upper and lower respiratory tract. Using this technology, we will identify the cell types involved in replication of VOCs and determine the critical changes in gene expression of these cells that affect replication of VOCs. In addition, our recent studies have revealed that SARS-CoV-2 targets peroxisomes during infection. These cellular organelles play a vital role in limiting viral replication and controlling inflammation. As such, we will compare how VOCs affect peroxisome functions relative to earlier strains of the virus. As we have shown that some peroxisome agonists can inhibit replication of early strains of SARS-CoV-2, we will explore the possibility of developing peroxisomal agonists as potential therapeutics against VOCs.",2021,2022,University of Alberta,398305.74,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +C13774,177708,Vaccine effectiveness against SARS-CoV-2 variants of concern in long-term care populations: a multi-province study,"Viruses can mutate and change over time, which results in new versions or variants that behave differently from the strain they originated from. Some variants of COVID-19 can spread more easily, faster, may cause more severe outcomes. These are called Variants of Concern (VOC) and their presence in a vulnerable population, such as individuals living and working in long-term care (LTC) homes, may make it harder to slow the spread of COVID-19 and control outbreaks. Within a few short months, several VOCs have become the predominant strains transmitted in our communities across Canada. In this project, we are proposing to explore the humoral immunity in vaccinated LTC workers, residents, and family members/caregivers of LTC residents against emerging VOCs. We will assess their ability to neutralize VOCs or detect VOC receptor binding domains in a standard ELISA (enzyme-linked immunosorbent assay). We will also study the association between humoral response, socio-demographic and pre-existing health conditions, and the healthcare outcomes (including hospitalization, emergency room visits, and mortality) in this population. This project will be the largest prospective cohort following workers, residents and caregivers of residents in LTC homes across Canada to explore their immunity against VOCs. Our large sample size will support more complex analysis (including regression and prediction modelling) and sub-analysis (by disease groups) in this high-risk population. The findings will provide decision-makers with guidance regarding vaccine effectiveness in this high-risk and highly vulnerable population.",2021,2022,Bruyère Research Institute/Institut de recherche Bruyère,399000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13775,177709,A Prospective Pan-Canadian Cohort Assessment of SARS-CoV-2 Variant of Concern Disease Severity and Association with Long-Term Symptoms in Children,"Over 160,000 children in Canada have been infected by SARS-CoV-2 and although, in general infection in children is milder than what occurs in adults, nearly 1,000 children have been hospitalized and 125 admitted to the intensive care unit. In December 2020, a SARS CoV-2 variant of concern (VOC), strain B.1.1.71, was identified. Data suggest that this VOC has increased transmissibility and is associated with increased mortality. Other VOC have been identified and some of these have the ability to decrease the effectiveness of natural and vaccine-induced immune responses. These VOC are present and spreading rapidly in Canada and there is an urgent need to understand their short and long-term impacts on children, particularly as this group of Canadians will be the last to be vaccinated and thus most likely to be exposed to natural infection. While data are scarce, a substantial proportion of individuals with COVID-19 develop persistent symptoms that are characteristic of long-term COVID symptoms (i.e. Long-Haulers). Symptoms in adults include fatigue, headache, shortness of breath, cognitive impairment, depression, skin rashes and gastrointestinal complaints. While there is a growing body of literature on long COVID in adults, the data on children are scarce. To address these knowledge gaps we will extend and expand two ongoing studies to enable: 1) The collection of acute and long-term data on both SARS-CoV-2 positive (VOC and non-VOC) and negative children thereby permitting an assessment of chronic symptoms and to compare those reported by these three otherwise similar groups of children. 2) Testing for VOC on specimens collected from asymptomatic SARS-CoV-2 test positive children to quantify and compare the secondary clinical attack rate between those positive for a VOC vs. those with non-VOC. 3) Quantify development of long-term symptoms in children with COVID and to extend follow-up from our current plan of 90 days out to a full 12 months.",2021,2022,University of Calgary,371165.76,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis | Post acute and long term health consequences",2021 +C13776,177710,Addressing gaps in our understanding of the mucosal immune response to SARS-CoV-2: Implications for transmission.,"Significant progress has been made in our understanding of systemic immunity to SARS-CoV-2, the virus that causes COVID-19. However much less is known about the mucosal immune response in the upper respiratory tract (the nose, mouth and throat). Based on data from our lab, we can detect antibodies to SARS-CoV-2 in the saliva of COVID-19 patients, and in some cases these antibodies bear the hallmarks of being produced in the local mucosal tissues. Prior to COVID we also discovered that antibody producing cells, particularly those produced at mucosal sites, can move about the body. However, in the context of SARS-CoV-2, we do not know how the mucosal immune response to natural infection is initiated, whether it is durable (maintained over time) and if it is effective at preventing asymptomatic infection against the ""original"" form of SARS-CoV-2 or its variants. We also don't know how vaccine-induced immunity in the upper respiratory tract compares with natural immunity. A better understanding of these questions is critical for predicting whether natural or vaccine-induced immunity prevents transmission against SARS-CoV-2 and its variant strains. In this study, we will take two approaches for addressing these gaps in knowledge. The first is to use an animal model to understand residence and trajectory of antibody producing cells in response to a de novo infection with SARS-CoV-2, or a recall response to SARS-CoV-2 in a pre-immune animal (conferred through natural immunity or vaccination). The advantage of the animal model is that we can assess antibody producing cells in different tissues of the body including the salivary glands, the lungs, the bone marrow and the gut. The second approach is to examine the mucosal immune response to SARS-CoV-2 in human populations that are highly exposed to the virus. Collectively these experiments will close gaps in our understanding of the mucosal immune response to SARS-CoV-2.",2021,2022,University of Toronto,322828.51,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C13777,177712,Pregnant and Lactating Individuals & Newborns COVID-19 Vaccination Study,"Pregnant individuals are a high-risk population for COVID-19 disease, with higher rates of disease severity, hospitalization, intensive care unit admission, and death compared to non-pregnant individuals. COVID-19 vaccines are one of the most powerful public health interventions to prevent and control the spread of COVID-19, and the inclusion of pregnant and lactating individuals in vaccine studies is critical. The Pregnant and LActating Individuals & Newborns COVID-19 Vaccination (PLAN-V) Study is a multi-site longitudinal study involving detailed data and sample collection to investigate the impact of COVID-19 vaccination in pregnancy on the immune responses of vaccinated individuals and their newborns. The PLAN-V Study will build on the successes of our previous study of pregnant individuals diagnosed with COVID-19 during pregnancy and assessment of placental transmission. We will evaluate the differences in immune response to COVID-19 vaccination and natural COVID-19 disease. Finally, to evaluate how pregnancy affects the immune response to COVID-19 vaccination, we will compare differences in the immune responses following vaccination of pregnant and non-pregnant individuals using data from our team's funded study on COVID-19 vaccination in the general population. PLAN-V will provide high-quality, real-time evidence to address key questions about COVID-19 vaccinations in pregnancy and the impact on newborn immunity. In doing so, the findings from our study will inform vaccine guidelines, support patient counselling by healthcare providers, and empower decision-making by Canadian families.",2021,2022,Ottawa Hospital Research Institute/Institut de recherche de l'Hôpital d'Ottawa,399000,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13778,177713,Evaluating the durability and cross-reactivity of SARS-CoV-2 immunity elicited by COVID-19 vaccines,"COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has advanced rapidly from initial clinical observations in late 2019 to a global pandemic. Safe and effective vaccines offer our best opportunity to control spread of infection, but limited availability of vaccine doses and rapid emergence of viral variants of concern that may evade vaccine-elicited immunity are major concerns in Canada and globally. ""Partial"" immunity elicited by one dose of vaccine may not protect some individuals, such as elderly adults, from infection by these new viral strains; however, we have an incomplete understanding of immune factors that may help to identify individuals or populations that remain at higher risk despite receiving the vaccine. Our project will compare the immune response in younger and older adults following one and two doses of COVID-19 vaccine. We will characterize the diversity of antibody-producing B cells generated following vaccination and link genetic features of these cells to each individual's ability to neutralize viral variants of concern. Our results will provide new information about vaccine-elicited immune responses and inform ongoing efforts to protect the most vulnerable members of our population.",2021,2022,Simon Fraser University,395010,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13779,177714,SARS-CoV-2 virus infection in vaccinated vulnerable populations and the potential for variant emergence,"Vulnerable populations including immunosuppressed individuals and those of older ages typically have less effective vaccine responses. Additionally, reports have surfaced that SARS-CoV-2 infection in particular vulnerable populations leads to viral variant emergence. Our research project will investigate the effectiveness of vaccination or previous infection in older frail individuals as well as HIV+ people to prevent infection with the SARS-CoV-2 variants of concern (VOC). As we are investigating the ability of antibodies elicited after vaccination to neutralize SARS-CoV-2 viruses, we will also determine the molecular signature of viruses that have the ability to escape antibody neutralization. We hypothesize that vaccinated vulnerable populations will be less protected from the variants which will enable a selection pressure capable of driving virus evolution and new variants. For our study we have established cohorts of infected and vaccinated vulnerable populations (older frail individuals and those HIV+) from Halifax, Nova Scotia; Sardinia, Italy; and Kigali, Rwanda. Plasma collected from these cohorts will be tested in virus neutralization assays and virus escape assays to identify protection as well as escape viruses. Viral variant signatures will be analyzed by next generation sequencing methods and our bioinformatic pipeline to identify regions of change on the virus that might affect antibody binding. To validate our work, we will perform challenge studies in vaccinated aged hamsters. Two important outcomes will result from this study: 1.Potential effectiveness of COVID-19 vaccines to protect against VOCs in vulnerable groups. 2.The signature of potential future VOCs. The VOC signature can be used to screen for potential VOCs in the community and inform vaccine reformulation.",2021,2022,University of Saskatchewan,398920.2,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe,,,,Canada,Canada | Italy | Rwanda,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity",2021 +C13780,177715,From idea to reality: COVID-19 Vaccination for Children and Youth,"COVID-19 vaccines for children and youth will soon be available. While serious acute ilness in children is rare, it can occur, underscoring the importance of vaccinating children and youth against COVID-19. Further, children and youth represent 21% of the Canadian population so vaccinating children and youth against COVID-19 is necessary for population-wide immunity. There are numerous unknowns including vaccine immune response, side effects, degree of protection for future COVID-19 infection among children and youth in addition to the perceptions of parents and healthcare providers about vaccinating healthy children and youth against COVID-19. In April 2020, we directed Canada's largest ongoing children's cohort study, TARGet Kids!, to understand the effects of COVID-19 on Canadian children and families. We conducted surveillance involving 1123 children to understand SARS-CoV-2 infection and symptoms, risk factors for infection, physical and mental health status and seroprevalence among children and their parents. We propose to build upon this work to understand COVID-19 vaccine effectiveness and safety among 2000 children and youth age 0-16 years and their parents. We will also understand COVID-19 vaccine uptake and use qualitative methods to understand COVID-19 vaccine hesitancy and decision-making among parents and healthcare providers. Rapid evaluation with a specific focus on children, youth and their parents will provide high-quality evidence to guide family-based policy interventions for COVID-19 vaccination for children. This study will provide needed information to inform vaccination policies for children and youth, provide confidence about COVID-19 vaccine effectiveness and safety for children and youth and contribute to a high degree of vaccine uptake so that society can return to normal functioning.",2021,2022,Unity Health Toronto,396503.06,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C13781,177716,Immune response after COVID-19 vaccination during maintenance therapy in immune-mediated inflammatory diseases: an observational cohort study (IMPACT),"The vaccines targeting SARS-CoV-2 (the virus causing COVID-19), are highly efficacious in preventing COVID-19 in the general population. Immune-mediated inflammatory diseases (IMID) such as rheumatoid arthritis, spondyloarthritis, inflammatory bowel disease, or psoriasis affect up to 5% of Canadians, many of whom are treated with immunosuppressive medications. Currently, the efficacy of COVID-19 vaccines in patients with IMIDs is not known since they were excluded from the original vaccine studies. Very little is also known about protection offered by the vaccines to immunosuppressed patients against new variants of SARS-CoV-2 that has spread across Canada. Therefore, our aim is to therefore conduct a study to determine whether patients with IMIDs on immunosuppressive medications mount an adequate immune response to COVID-19 vaccines. We plan to recruit a total of 600 subjects (525 with IMIDs treated with immunosuppressive treatment as well as patients not on such medications, and 75 healthy controls). We will collect blood samples before, and at four-to-five time-points after, COVID-19 vaccination. We will then test these blood samples for antibody responses as well as cellular immune response using our established laboratory methods to determine whether immune response to vaccination is compromised in IMID patients treated with immunosuppressive therapy. We will also determine the immune response against new variants of the SARS-CoV-2 virus. The results of this study will determine whether IMID patients treated with immunosuppressive medications still generate a protective immune response to the original SARS-CoV-2 and new variants after COVID-19 vaccination. We will then ensure that all stakeholders - patient groups, public health administrators and policy makers- are informed, and recommendations made for appropriate vaccination schedule for these potentially vulnerable patients.",2021,2022,University Health Network,398840.4,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13782,177717,Intranasal multivalent vaccines targeting COVID-19 variants of concern,"The COVID-19 pandemic, caused by SARS-CoV-2, is being fuelled by emerging variants such as the ones first detected in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (P.1) and now more recently in California (B.1.427/B.1.429). These variants have mutations in the receptor binding domain (RBD) of the spike protein (S protein) and they are spreading rapidly in many countries, including Canada. A recent human study of the Pfizer mRNA vaccine found that it was significantly less effective (neutralizing antibody titer reduced by two thirds) at neutralizing the B.1.351 variant. This suggests that the currently approved vaccines may not be effective against these variants of concern (VOCs). The goal of our work is to develop multivalent vaccines capable of combating more than one variant simultaneously. Using a helper-dependent adenoviral vector (HD-Ad), we have successfully developed in the past two highly effective COVID-19 vaccines: one expressing the SARS-CoV-2 RBD and the other expressing the full-length S protein. Since HD-Ad vectors are devoid of adenoviral coding sequences, they have a superior safety profile and a large cloning capacity for transgenes. These features make HD-Ad an excellent vaccine platform and one that is ideal for the construction of multivalent vaccines simultaneously targeting multiple VOCs. In this work, we will construct two HD-Ad based multivalent vaccines and examine their immunogenicity and protective efficacy in animal models. These two multivalent vaccines will be representative of the main SARS-CoV-2 variants currently circulating in the human population. We anticipate that intranasal delivery of HD-Ad based multivalent vaccines targeting SARS-CoV-2 and the VOCs will be highly effective in controlling the current and future waves of this pandemic. Significance: The development of multivalent vaccines capable of combating SARS-CoV-2 and the three main VOCs will greatly facilitate efforts to control this pandemic.",2021,2022,University of Toronto,398533.97,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C13783,177718,"Evaluation of COVID-19 antibodies, cell-mediated immunity and telomeres following COVID-19 immunization or natural infection in an immune compromised population: An HIV Cohort Study","Due to a critical need, vaccines against SARS-COV-2 were developed and introduced into practice in record time. This has led to a lingering uncertainty about vaccine efficacy and safety in immune compromised populations, such as persons with HIV (PWH), not specifically studied in the registration trials. There is also little data published in PWH on the immunologic response to COVID-19 infection or immunisation when stratified by age or CD4 count. As both may carry major clinical implications for poor immunity, an in-depth assessment of natural and vaccine-mediated immune response to COVID-19 in PWH is needed. We aim to assess the initial antibody response and its rate of decline and also levels of cell-mediated immunity (CMI) in PWH after COVID-19 infection or vaccination. Factors including age, sex, ethnicity, CD4 nadir, HIV viral suppression, antiretroviral therapy, co-morbidities, co-infections, vaccine type and COVID-19 variant strains will be correlated with loss of COVID-19 antibodies and markers of CMI. We will also study the association between telomere length and COVID-19 disease severity and vaccine-mediated immune response. We will use a well characterized longitudinal cohort of >2020 PWH accessing care at the Southern Alberta Clinic (SAC) and the comprehensive database that routinely collects data on the clinical and demographic factors listed above. We will identify PWH who have i) had COVID-19 infection or ii) received a COVID-19 vaccine or iii) declined immunization between 01/07/2021-01/07/2022. As routine care, bloodwork is obtained quarterly, and aliquots are stored in a biobank. Using both stored and prospective samples we will test for antibody response, markers of CMI and changes in telomere length associated with COVID-19 disease and vaccine. This will be linked to the database to stratify our analysis and evaluate confounding and effect modification. This work will assess severity of COVID-19 disease and efficacy of vaccination in PWH.",2021,2022,University of Calgary,346854.69,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13784,177719,Assessing Immunogenicity of Covid-19 Vaccines in Survivors of Hematological and Solid Cancers,"New vaccines developed against SARS-CoV-2 are being distributed to provide individual protection and eventually, herd immunity. As many cancer survivors have weakened immune systems due to their cancer and their treatments, it is not known how effective these vaccines will be in cancer survivors and whether dosing regimens approved for the general population will be appropriate. To address these issues, we propose to enroll a total of ~1000 survivors of either blood or solid cancers into a study of Covid-19 vaccine immunogenicity. Participants will be categorized as to their types of cancer, types of treatment and extent of immune reconstitution. Blood samples will be collected prior to the first vaccine dose, between the first and second dose at a time dependent upon the dosing regimen prescribed or 30 days after the first dose if a single dose regimen is prescribed. Antibody levels before, between and after immunizations will be measured against SARS-CoV-2 spike protein and SARSCoV-2 spike protein receptor binding domain (RBD) by ELISA. Surrogate ELISA SARS-CoV2 neutralization assays and pseudovirus neutralization assays will be done with samples shown to have anti-SARS-CoV-2 antibodies. Levels of antibodies measured by ELISA and SARS-CoV-2 neutralization titre will be compared between groups of cancer survivors and with an age/sex matched control group of 50 healthy persons. Subsets of cancer survivors with high (n = 50) versus low (n = 50) levels of anti-SARS-CoV-2 antibodies will be tested for T cell reactivity against SARS-CoV-2 by ELISPOT assays with synthetic peptides. Results obtained should provide information on which cancer survivors will benefit from standard vaccination protocols and which will require modified protocols to obtain benefit",2021,2022,Memorial University of Newfoundland,303160.2,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C13785,177720,Canadian COVID-19 Emergency Department Rapid Response Network: Determining Real-World Vaccine Effectiveness and Duration of Protection Against Variants of Concern,"The COVID-19 pandemic is the most significant global public health crisis in over 100 years. Despite recent progress with vaccination, more contagious and deadly variants of the COVID-19 virus have emerged. Our project aims to determine vaccine effectiveness against the COVID-19 virus ""variants of concern"". In April 2020, we founded the Canadian COVID-19 Emergency Department Rapid Response Network to help in the fight against the pandemic. Our network includes 50 Canadian emergency departments from across 8 provinces. The network collects information from the hospital charts of every emergency department patient tested for COVID-19. Our initial goal was to use this information to inform health care personnel and decision-makers about the best way to care for patients with COVID-19 in the emergency department. We propose the use of our network and database to answer new questions about how well COVID-19 vaccines work in the real world. Using data from Ontario patients in the database, we will focus on understanding how well vaccines work for specific variants of the COVID-19 virus. By linking our data with a unique database called the ""Ontario Health Data Platform"", we will be able to get very accurate details about each patient's vaccination history and COVID-19 test results. By comparing the vaccination status of patients who test positive for specific COVID-19 variants against those who test negative, we can determine vaccine effectiveness against specific variants. Also, we will be able to determine whether vaccines prevent severe illness caused by variants, even when vaccinated individuals get infected. This information is critical for our public health partners and decision-makers in the government to guide the choice of vaccines to be delivered according to the type of variants circulating. Our project will support policy decisions aiming to end thes pandemic quickly and protect as many people as possible.",2021,2022,Queen's University,395914.93,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +C13786,177721,A Qualitative Exploration of Vaccine Uptake and Hesitancy Among People Experiencing Homelessness in Toronto,"Homelessness is a public health crisis in Canada, exacerbated by the COVID-19 pandemic. People experiencing homelessness face disproportionate physical, mental, and social burdens, risk factors for poor outcomes if infected with COVID-19. Those living in shelters are at higher risk for contracting COVID-19 because of shared living spaces, crowding, difficulty physical distancing, and high population turnover. Once infected with COVID-19, people experiencing homelessness have a higher likelihood of hospitalization, intensive care unit admission, or death than the general population. Given increased risk for exposure and serious infection, homeless individuals who live in congregate settings are a priority population for the vaccine rollout in Canada. However, vaccination rates among people experiencing homelessness are historically lower than the general population, linked in part to vaccine misinformation and mistrust of healthcare systems and providers. No Canadian studies have yet investigated COVID-19 vaccine uptake and hesitancy among this population. This qualitative study will explore reasons for COVID-19 vaccine uptake and hesitancy among people experiencing homelessness. Over 3 months, we will interview a diverse group of up to 40 homeless individuals living in physical distancing hotels and emergency shelters in Toronto, to better understand opinions, beliefs, and attitudes towards the COVID-19 vaccine. This study will be conducted at MAP Centre for Urban Health Solutions and leverages existing partnerships with City of Toronto and Canadian Alliance to End Homelessness. Findings will be rapidly communicated to our public health partners to develop more targeted interventions and strategies to improve vaccination rates among homeless individuals. COVID-19 has disproportionately impacted people who are homeless and this study will create evidence to address this health inequity.",2021,2022,Unity Health Toronto,80005.88,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C13787,177722,Examining Drivers of Vaccine Hesitancy and Approaches to Improve Vaccine Confidence in Canada,"The COVID-19 pandemic has resulted in over 138 million infections globally. Extensive efforts have been made to keep the public accurately informed of evolving information and public health recommendations. However, variable levels of public trust in both non-pharmaceutical (e.g. masking, hand washing) and pharmaceutical (e.g. vaccination) public health recommendations have been identified. Health Canada has approved several vaccines for COVID-19, and health officials estimate that vaccination in 70-80 percent of the population is required for community immunity (i.e., when most of a population is immune to an infectious disease, providing indirect protection) to be achieved. Understanding the underlying reasons why Canadians are vaccine hesitant within the general public and healthcare workforce is crucial to developing effective approaches to improve levels of vaccine confidence in Canada. In response to this challenge, we propose to co-design, with members of the public, a suite of targeted population level solutions to support public confidence in vaccination for COVID-19. We will achieve this through three overlapping phases of work: Phase I National Survey: design and administration of survey to a representative sample of Canadians and healthcare workers to examine underlying drivers of vaccine hesitancy and confidence, strategies for effective communication of vaccination information, and identification of socio-demographic variations. Phase II: Follow up focus groups within key sub-populations (e.g. sex, age, ethnicity etc.) based on survey findings to develop a richer understanding of contextual factors, and Phase III: Design evidence informed interventions to improve levels of public trust and influence increased rates of vaccination. Interventions will be funnelled into an existing CIHR funded national COVID-19 awareness campaign that is currently being led by our team.",2021,2022,Dalhousie University,200483.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2021 +C13788,177723,Addressing socioeconomic and racial/ethnic inequities in COVID-19 vaccine hesitancy among parents and adolescents,"There is little information that is known about COVID-19 vaccine hesitancy or intentions among parents or teens in Canada. The success of COVID-19 vaccination campaigns for children and youth will be driven by the willingness of parents and adolescents to accept the vaccine. Gaining support for the vaccine for children and youth may be particularly difficult as severe COVID-19 in children and teens remains rare. This project aims to understand the determinants of vaccine hesitancy among parents and adolescents in Montreal and to develop strategies to address inequalities in vaccine acceptance. For this project, we will extend a current cohort study (Enfants et COVID-19: Etude de seroprevalence, EnCORE) which includes two of Montreal's most disadvantaged neighbourhoods. Our objectives are to monitor vaccine hesitancy and uptake in parents and teens through online questionnaires and also to engage with community members to better understand attitudes and perceptions of COVID-19 vaccination. For community engagement, we will create teams of parents and youth that will actively guide the research process with the goal of designing innovative solutions to address vaccine hesitancy in their communities. This research will address knowledge gaps about COVID-19 vaccine hesitancy among parents and adolescents and will use participatory approaches to generate in-depth understanding of vaccine hesitancy and develop community-driven solutions to lessen COVID-19 vaccine inequalities.",2021,2022,Université de Montréal,381990.63,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C13789,177724,Big data and little behaviours: audit and feedback with or without a quality improvement toolkit to help primary care facilitate COVID-19 vaccine uptake,"One of the most important ways to address vaccine hesitancy and build vaccine confidence is through conversations with a trusted health professional. People trust their primary care professionals to provide them with personalized recommendations based on an understanding of their whole lives. So, how can we best help primary care professionals to have effective conversations about the COVID vaccines with their patients who most need their help? This proposal is about implementing a province-wide strategy that uses ""big data"" to enable a sequence of little behaviours to bring us closer to herd immunity. The foundation for our approach is using registry data about vaccine uptake and linking it to datasets that identify the main family doctor for each person. The doctor will get a list of people in their practice who are 'overdue' for the vaccine (e.g., age over 80 and not yet vaccinated). As experts in behavioural science, we know there is more to solving this problem than simply providing a list. That's why alongside this list we will be testing a set of tools to help the doctor to take the steps needed to effectively engage with each of their patients who need their support. We will carefully test whether the list, with or without the additional toolkit, increases vaccine uptake, in which types of primary care settings, and for which types of patients. We will specifically look at whether this strategy helped improve the fairness of vaccine uptake - that is, whether it helped get more people in hard-hit communities to get vaccinated.",2021,2022,Women's College Research Institute,398961.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C13790,177725,Unpacking COVID-19 Vaccine Hesitancy in Canada,"Vaccination against COVID-19 is key in ending the pandemic. However, many Canadian adults can be unsure or fearful of vaccination. Many experts consider that the negative content about vaccination that circulates in online social media can have a negative impact on people's willingness to be vaccinated against COVID-19. However, most of the research on how people make decisions about vaccination and on the influence of online (mis)information on attitudes toward vaccination have focused on parental decisions about childhood vaccination. In this project, we will explore reasons why some Canadian adults hesitate to receive COVID-19 vaccines, what sources of information they trust and what is the impact of online information on COVID-19 vaccines on their attitudes. We will also describe 'fake news' that circulate in social media in Canada and identify the characteristics that make them become 'viral'. Finally, we will investigate innovative, fun and interactive tools leveraging digital technologies to deliver positive messages on COVID-19 vaccination.",2021,2022,Université Laval,398896.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C13791,177726,Developing the VACCINE (VACine Confidence and ImmuNization Education) Checklist to support COVID-19 vaccine confidence and uptake among workers in long-term care,"High levels of vaccine hesitancy among long-term care (LTC) workers, who are among the first to be vaccinated, has been observed globally. Despite a growing understanding of the factors affecting vaccine confidence among healthcare workers and a wide range of tools developed, few have been evaluated for their efficacy in promoting vaccine uptake in this population. This project will leverage the nine behavioural science principles outlined by the Ontario COVID-19 Science Advisory Table to develop a VACCINE (VACine Confidence and ImmuNization Education) Checklist to support COVID-19 vaccine confidence and uptake among LTC workers. We will leverage and assess current efforts to build vaccine confidence and contribute to the future development of high-quality educational tools for COVID-19 and other vaccines. Our goals are to: (1) Develop a checklist to guide the development of vaccine confidence and immunization education programs, called VACCINE, that can assess the quality of educational tools and strategies; (2) Conduct an environmental scan for COVID-19 vaccine education strategies directed at LTC and other healthcare workers. We will identify barriers between knowledge creation and knowledge use, and compile a list of measurable outcomes to be considered for future evaluation of vaccine education strategies; (3) Assess the attributes of existing educational tools and initiatives targeting vaccine confidence against the VACCINE Checklist; (4) Select, tailor and implement appropriate educational strategies to address vaccine hesitancy and boost vaccine confidence within the LTC sector. These will be co-designed with Nurse Practitioner-Led Outreach Teams (NLOTs) and LTC homes and tailored to meet the needs of their specific workforce population, culture and context; and (5) Monitor and enhance knowledge uptake using a developmental evaluation process to enable continuous improvement in the implementation of educational strategies.",2021,2022,Bruyère Research Institute/Institut de recherche Bruyère,206510.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C13792,177727,Reducing COVID-19 Vaccine Hesitancy in Canadian Immigrants,"The roll-out of COVID-19 vaccines in Canada and elsewhere has created considerable optimism that the worst days of the pandemic are behind us and that life will soon return to normal. While some optimism is justified by the promise of vaccines, the extent of the optimism is not yet warranted. Apart from the risks associated with COVID-19 variants, vaccine hesitancy remains a profound challenge to public health. Reducing vaccine hesitancy is likely to require different approaches for different communities, but we do not have a sufficiently nuanced understanding of differences in vaccine attitudes across the country. First- and second-generation immigrants constitute nearly 40% of the Canadian population, but we have inadequate data about vaccine hesitancy in immigrant groups or data about the differences in immigrant communities as a function of generational status, ethnicity, or sex. A deeper and more nuanced picture of vaccine hesitancy in immigrants is thus essential to ending the pandemic. Vaccine hesitancy has traditionally been characterized as a consequence of the ""war on science,"" including the ""death of expertise."" There is considerable evidence, however, that this view is mistaken. Vaccine hesitancy actually reflects a crisis of trust, but we know very little about the attitudes of immigrants regarding public institutions or about the effect of differences of generational status, ethnicity, or sex on these attitudes. Improving vaccine uptake in Canada will not be achieved by giving Canadians a reason to believe in public health messaging regarding COVID-19 but by giving them a reason to trust the messengers, and a successful public health approach will require targeting messaging to match the attitudes of a particular community. The question of how to do that for diverse immigrant communities is the focus of this project.",2021,2022,McGill University/Université McGill,267915.73,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C13793,177728,"SAME PAGE: Bridging the gaps between high-quality clinical research evidence for COVID-19 and clinicians, guideline developers, and policy makers","Due to worldwide interest in COVID-19, over 300 research articles are published daily. However, only a small fraction of these articles are of high enough quality to be used to change how COVID-19 is managed. COVID-19 Premium Literature Service (COVID-19+ EA) is a university-based service that uses computers to search for COVID-19 artricles nightly, and then uses trained human researchers to sort the high-quality articles from the low-quality articles. The titles of these articles are currently posted on a free website that is used by clinicians, guideline developers, public health officers, and is open to the public. The purpose of this grant is to achieve 2 objectives. (1) To find more efficient ways to select the articles that our human staff must read. The high number of daily articles makes manually checking them for quality very time-consuming. To help with this task, we have trained a computer to search for words and phrases that more frequently appear in high-quality articles (called machine-learning, a form of artificial intelligence). Early results are promising, but we need additional testing against our human readers to be sure the computer doesn't discard any high-quality articles by mistake. (2) To add 2 new services to COVID-19+ EA. One new service will be a focused search for articles on COVID-19 vaccines. These articles will be checked for quality and kept in a separate collection. The other new service will pull out data on sex, age, and race from all high-quality articles and label the ones that report results separately based on these features. These new collections will help researchers identify patterns that may not have been obvious in any single study alone. By supporting and improving COVID-19+ EA, this grant will help make the SAME high-quality evidence accessible to everyone in a form that is tailored to their needs. In turn, this evidence will be used to help prevent, diagnose, and treat COVID-19 in Canadians.",2021,2022,McMaster University,144537.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +C13794,177729,Overcoming emerging COVID-19 challenges with relatable science: Developing and evaluating knowledge tools for Canadians,"We have an established program through which we co-create knowledge tools with parents. These tools cover a range of common conditions for which parents seek pediatric healthcare. Currently we have 24 tools (www.echokt.ca) that merge the best available science about how to manage the conditions with the power of parent experiences. Over the past 16 years, we have learned that the strategic merger of the best available science couched within the persuasive power of experience makes science more relatable. We will re-focus our work to create knowledge tools about COVID19 to increase the public's confidence in science and to encourage vaccine uptake and maintenance of ongoing public health measures (social distancing, mask use). Our proposal involves four parts. First, we will conduct interviews/focus groups with families (including diverse community groups, those with low health literacy, and those whose first language is not English) to understand their concerns about COVID19, particularly in response to vaccine hesitancy and other public health measures. It is anticipated that vaccine hesitancy will emerge as a challenge with children and young adults given the low incidence of significant morbidity experienced with COVID19. Second, we will develop infographics and videos that merge parent experience with the best available science to address the knowledge needs identified. Third, we will undertake usability testing to ensure that our tools meet the needs of Canada's diverse population. Fourth, in collaboration with several established national networks, we will disseminate the knowledge tools through a structured social media campaign using platforms and methods (e.g., influencers) known to increase uptake of health messages. We have long-standing relationships with many provincial/national groups and we have an established parent advisory group and a virtual, national parent network that will provide critical input at all stages of development and evaluation.",2021,2022,University of Alberta,217431.06,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +C13795,177730,Identifying strategies to (re)build trust in Canadian social institutions and increase public acceptance of COVID-19 countermeasures,"Canadians' trust is critical for the acceptance of official countermeasures designed to reduce the transmission of SARS-COV-2. Problematic then is data reporting decline in the overall trust of political leadership in Canada (32% in 2021 vs. 39% in 2020), and reports on public concerns with the way the pandemic has been handled (e.g. significant criticism regarding the rollout of vaccines in comparison to other OECD countries). Anti-mask rallies, blatant disregard for restrictions related to social gatherings and circulation of disinformation regarding vaccine safety and efficacy suggest there is public distrust in social institutions, particularly with regards to the management of the pandemic. Through interviews and a national survey, we will identify the nature and extent of Canadians' trust in social institutions, particularly as it relates to the acceptance of measures to reduce COVID-19 transmission (e.g. vaccine uptake, social distancing, lockdowns, wearing a mask). Drawing on these data, we will develop tailored strategies to (re)build public trust in social institutions as a means for increasing public acceptance of measures. Through our established infrastructure for dissemination, we will target public health decision-makers, communication specialists and community leaders nationally. Our strategies will be promoted to individuals across social institutions involved in pandemic management, from high level government officials to individual public health units. Importantly, we will take a targeted approach to translation, identifying knowledge users as data illustrate populations where strategies to build trust are most needed. Ultimately our goal is to develop and disseminate real-time strategies that will (re)build trust in social institutions responsible for pandemic management to foster greater acceptance of measures to reduce SARS-COV-2 transmission.",2021,2022,University of Waterloo,172689.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C13796,177731,Vaccine Outreach Integrating Community Engagement & Science (VOICES): Addressing COVID-19 Vaccine Hesitancy and Promoting Uptake among Racialized Sexual and Gender Minority Populations,"The rapid development of COVID-19 vaccines is a huge scientific achievement; to be effective, however, people must get the vaccine. With disparities in COVID-19 infections and severe disease outcomes among marginalized populations in Canada, vaccination is crucial; yet racialized sexual and gender minority people are among those least likely to be vaccinated-they are also under-represented in pandemic response planning. Systemic discrimination, economic and health inequities, and past unethical medical research heighten distrust of vaccines and health authorities, posing barriers to COVID-19 vaccination. ""Vaccine hesitancy"" (VH)-delays in acceptance or refusal of vaccination, even when vaccines are available-is often attributed to anti-vaxxers and 'deficits' in scientific literacy among 'lay people'. However, WHO and leading research emphasize the need to examine multilevel drivers of VH among specific populations and locations-structural factors (e.g. sociocultural, historical, health system, economic); social and community influences (e.g. community norms about vaccination, COVID-19 stigma)-and for specific vaccines, such as COVID-19. VOICES, an ethnoracially-, gender-, and sexually-diverse multidisciplinary team, will apply a Public Understanding of Science framework and mixed methods-an online survey with discrete choice analysis, follow-up community focus groups, and participatory video to: 1) Explore local understandings of COVID-19 and VH among racialized sexual and gender minority communities in the Greater Toronto & Hamilton Area; 2) Examine multilevel structural and social factors associated with VH; and 3) Engage with community partners in knowledge mobilization to reduce COVID-19 VH and promote informed decision-making. VOICES will accelerate the availability of high-quality and real-time evidence to support Canada's COVID-19 response by enhancing public and 'expert' understanding, dialogue, and COVID-19 vaccination among marginalized populations.",2021,2022,University of Toronto,298702.57,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy | Community engagement,2021 +C13797,177732,Knowledge mobilization activities to support decision-making by public citizens using a systematic and living map of evidence and recommendations on COVID-19,"The COVID-19 pandemic has caused rapidly evolving science, mixed public health and political messages and frank misinformation. With global partners, Cochrane Canada has produced a widely used repository of over 1,200 critically appraised COVID-19 recommendations with a large global network of collaborators (covid19.recmap.org). The work involves prompt identification, evaluation, and extraction of newly published guideline recommendations (and the supporting research evidence). This proposal outlines research to extend this CIHR-supported work (funding ends June 2021) by enhancing the uptake of these recommendations with defined users. We wish to maximize the impact of COVID-19's rapidly evolving science and recommendations through 'highly effective' plain language recommendations for all citizens. This project will use high quality methods, building on existing plain language templates and approaches to create accessible trustworthy COVID-19 recommendations. In addition to maintaining the repository, the key additional activities include: (1) developing and testing, through high quality research, plain language versions of priority recommendations with adolescents, parents and general adult citizens; (2) working with high profile decision-makers from among our high-profile partners in Canada and globally, such as the World Health Organization (WHO) to provide tailored support for adapting and implementing recommendations; and (3) integrating new resources for use by decision-makers when implementing COVID-19 recommendations. Our team provides internationally recognized expertise in knowledge synthesis and mobilization, living guidelines, randomized trials, capacity-building, and content relevant to specific priority populations. Together, this work will further improve comprehensibility, comprehensiveness and use of COVID-19 recommendations by more stakeholders, including public citizens and health care professionals that desire plain language recommendations.",2021,2022,McMaster University,793147.36,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication,2021 +C13798,177733,Mitigating COVID-19 variant spread by leveraging social psychological and neurobiological markers to optimize public health communications during the first vaccine rollout.,"Effective messaging to promote COVID-19 mitigation behaviors is critical for drawing the pandemic to a close in Canada. Research across several health domains suggests that messaging that employ 3 elements-vivid imagery, making other's mitigation behaviours salient (norms), and promote accepting short-term pain for long-term gain-increase protective behaviour. Additionally, research has found that messages that engage brain systems involved in attention capture and self-reflection are more likely to be acted upon. This project will use state-of-the-art theory and methods to identify optimal strategies for motivating COVID-19 mitigation behaviors in the pandemic's post-acute phase. Study 1 will be a 2-wave population on-line cohort survey of 2000 adults who have not received any vaccine shot. They will answer questions on key beliefs about COVID-19 and relevant behaviours (Wave 1). They will be randomly assigned to view 4 PSAs that vary in whether they are vivid, provide information about others, and highlight long-term benefits of protective behaviour. They will then rate the 4 PSAs on quality, emotional impact, informativeness, and perceived effectiveness. At Wave 2 (4 months later), respondents will answer a survey with the same measures on beliefs and behaviours since Wave 1, including vaccination status and other mitigation behaviors. We hypothesize that those viewing PSAs that are vivid, emphasize norms, and make long-term benefits salient will be more likely to have engaged in mitigation behaviours (e.g., getting vaccinated). Study 2 will be a lab study where participants will view all PSAs, and rate each on the same Study 1 dimensions. Eye tracking technology and functional near-infrared spectroscopy (fNIRS) will identify which PSAs are most attention-capturing and lead to deepest self-reflection. These studies will identify which COVID-19 PSAs are most effective for promoting vaccination and other mitigation measures for the current and future pandemics.",2021,2022,University of Waterloo,396258.87,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C13799,177734,Global Impact of COVID-19 in Cystic Fibrosis: An International Collaboration,"Cystic fibrosis (CF) is a multi-system genetic condition that affects nearly 90,000 people globally, for which there is no cure. In addition to managing other complications including CF-related diabetes, malnutrition, and progressive lung damage, those with CF are susceptible to frequent lung infections. To date, the impact of the devastating COVID-19 pandemic on the CF population is not well-understood, and very little is known about the disease course and long-term effects of COVID-19 on this medically vulnerable population. Fortunately, CF is one of the few rare diseases with well-established, national patient databases. These databases contain a wealth of health information, spanning the lifetime of someone living with CF, and using this information, the CF community is well-positioned to answer important questions about COVID-19 quickly and efficiently. This project will aim to answer 3 questions in the CF population: 1) What are the risk factors including sex and other factors that predict poor outcomes following infection? 2) What is the medium- and long-term impact of infection? 3) What are the factors that influence CF health outcomes after COVID-19 in those who have received a transplant? Using national CF databases, we will capture everyone with CF with a confirmed COVID-19 infection between January 1, 2020 and March 31, 2022, and follow these individuals until June 30, 2022, to ensure at least 3 months of follow-up information to assess post-COVID-19 health. Given what is known about the general population, for our CF population, we will consider risk factors such as: age, sex, race/ethnicity, complications, baseline lung health, nutrition, geography (country) and socioeconomic status. Our work will provide vital knowledge about who is at the highest risk for poor health outcome or disease course following COVID-19 infection, so that people with CF and their care teams can make informed choices about exposure risk",2021,2022,St. Michael's Hospital,291270,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2021 +C13800,177735,Autoimmunity as a novel mechanism in post-COVID syndrome,"After recovering from COVID-19, many people keep having bad health outcomes, with an increased risk of hospitalizations and death compared to similar people who did not have COVID-19. Moreover, even if not requiring hospitalization, many of them continue to suffer for a long time from low health-related quality of life, with cognitive dysfunction (""brain fog""), sensory losses (taste, smell) and weakness. This has been termed ""Long COVID"" in the common media, or post-COVID syndrome in the medical world. The reason for this is currently unknown, yet it is likely related to a similar syndrome that affects people after other severe diseases, called post-ICU (intensive care unit) syndrome. In this application we propose to study the post-COVID syndrome and its relationship with post-ICU syndrome. Our main hypothesis is that autoimmunity plays a role in post-COVID syndrome, and we intend to study it in 3 aims: 1) Map the autoimmune landscape of acute COVID-19 by assessing a broad variety of autoantibodies among severe COVID-19 patients over time, and their association with specific organ dysfunction 2) Study the development of these autoantibodies using immune mediators and measurements of immune cells. 3) Validate our findings in long-term post-COVID patients, to see if the same autoantibodies and the same organ dysfunction happen to them as well. Our findings would allow us to understand the role of autoantibodies in post-COVID syndrome. This knowledge would facilitate the use of existing immune-modulating medications to help treat patients with post-COVID syndrome and even prevent it from happening.",2021,2022,St. Michael's Hospital,215061,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2021 +C13801,177736,"Post-Acute Complications of COVID-19: An International Cohort Study (PACS) Note that in a previous iteration, this proposal was titled PACMAN as indicated in some of the Letters of Support","There are nearly 130 million COVID-19 survivors worldwide and this number is likely to increase. Early reports suggest that COVID-19 survivors might have symptoms that last more than a month after the infection. There is little high quality information about what these symptoms are and how common they are in COVID-19 survivors. Also little is known about whether there are effects of COVID-19 on physical measurements like tests of lung function, muscle strength and blood pressure that last after recovery from the initial infection. In this study, we will measure how often COVID-19 survivors develop physical complaints and abnormalities in different physical measurements. We will conduct this study in approximately 50,000 adults from about 20 countries. We expect that about 1000 of these individuals have had COVID-19. We will be able to compare their physical complaints and measurements with the physical complaints and measurements of the roughly 49,000 study participants who have not had COVID-19. We will then use sophisticated statistical techniques to paint a picture of the ""post-COVID"" patient. Once we have an accurate idea of the ways in which COVID-19 patients can be affected after they are over the initial infection, we will be able to identify what characteristics put them at risk for these late COVID-19 complications.",2021,2022,McMaster University,395555.83,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C13802,177737,Exploring Rehabilitation Needs and Access to Services for Long COVID,"Many people in Canada have had COVID-19. Months after acute COVID-19 is over, many people keep having symptoms that affect their ""normal"" daily functioning. This condition is called ""Long COVID"". Very little is known or understood about Long COVID. It has been estimated that almost 1 out of 7 people who get COVID-19 will develop Long COVID. But we don't know what specific problems they experience. We also don't know what type of health care or rehabilitation they need. There are many barriers to accessing health care. These include access to rehabilitation. People in rural/isolated areas have fewer health care options than people in cities. People with lower incomes face barriers to healthcare. Concerns or past negative experiences with the healthcare system may be a barrier. COVID-related restrictions on travel and gathering create more barriers to accessing health care. Learning from people with Long COVID is critical to understanding its impact. Patient views and experiences should help us know how to best treat Long COVID. Current treatment guidelines recommend self-management or rehabilitation. But these guidelines are based mainly on the opinions of experts. The views and preferences of patients have not been studied. We will interview people with Long COVID to better understand their health problems and rehabilitation needs. We will learn if they are getting the help they need for their condition. We will also ask about their experiences with rehabilitation and the health care system. Lastly, we will ask how well currently available services met (or did not meet) their needs. Our results will allow us to make specific recommendations to help people with Long COVID get the help and rehabilitation they need. Results will help improve rehabilitation for Long COVID in Canada and inform international rehabilitation guidelines. (The research team for this project includes people living with Long COVID.)",2021,2022,University of Alberta,121916.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Indirect health impacts",2021 +C13803,177738,In people with Long Covid does adding a digital health platform to usual care improve outcomes at three months compared to usual care alone? The Enhancing Covid Rehabilitation with Technology (ECORT) randomised controlled trial,"About one in five people who test positive for covid-19 continue to have symptoms for longer than five weeks. Similar long-term consequences of infection were described by physicians following the Russian Flu in the 1890's, the Spanish Flu in 1919 and more recently after SARS and MERS. The commonest symptoms are fatigue and breathlessness, but symptoms are highly variable and have been described involving most body systems. The variety of different presentations makes describing a clear treatment pathway difficult. Currently, rehabilitation for Long Covid involves education, symptom management, managed goal setting and support in navigating the health system. In other chronic disorders, symptom tracking, changing treatment in response to alterations in symptoms (measurement-based care) and case management are more effective than usual care in improving outcomes. There is some evidence that these activities can be delivered more effectively using digital platforms, usually with a patient-facing app and a clinician-facing dashboard. There have been no trials of such platforms in Long Covid rehabilitation programs. This study aims to complete a randomized controlled trial in people with Long Covid to test the effectiveness of a digital health platform, NexJ (https://www.nexjhealth.com/). Participants will be recruited from two specialist Long Covid rehabilitation clinics. The main aim of the study is to see whether, in people with Long Covid, adding NexJ to usual care improves quality of life after 12 weeks compared to usual care alone. We will also ask participants about their experience of using NexJ. As part of the trial, we will examine the cost-effectiveness of NexJ and the best way to implement it. If we show NexJ improves outcomes it has the potential to be rapidly rolled out in Canada to provide personalized rehabilitation for people with Long Covid.",2021,2022,Ottawa Hospital Research Institute/Institut de recherche de l'Hôpital d'Ottawa,736449.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C13804,177739,Post COVID hyperinflammation: A syndrome beyond the name,"COVID-19 can threaten the live of previously healthy children. Multisystem Inflammatory Syndrome in Children (MIS-C) develops weeks after a mild or even asymptomatic COVID-19 infection. Each wave of infections is closely followed by a wave of children across Canada and around the world presenting to hospital in shock and heart failure due to MIS-C, an uncontrolled post-COVID-19 inflammation. MIS-C closely resembles Kawasaki Disease (KD). KD causes fever and inflammation of blood vessels, most importantly the coronary arteries feeding the heart. Similar to KD, one in four children with MIS-C develops coronary artery disease. It is critical to enable health care teams to rapidly identify high-risk children with MIS-C and control the life-threatening inflammation before it damages the child's heart. Our team has studied and dissected the reasons responsible for inflammation leading to shock and hyperinflammation in KD and have identified key biomarkers and optimal targets for treatment. These have been rapidly translated to the bedside resulting in new medications and improved outcomes. We urgently need to transfer these lessons to children with MIS-C and provide the desperately needed evidence to guide development of effective therapeutic approaches. Our team includes doctors, scientists, and families working together to tackle this serious disease. We will use machine learning and artificial intelligence strategies to analyze and integrate complex biologic and clinical data, in order to rapidly diagnose MIS-C and identify the children at highest risk. We've successfully done this before in other diseases. We already have a strong and deeply committed Canada-wide team, expertise and infrastructure in place from our other successful projects and national networks. We have international partner networks across Europe and the USA to share our discoveries most efficient and save the lives and protect the hearts of affected children around the world.",2021,2022,Hospital for Sick Children,398337.66,Other,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C13805,177740,Biomarker Discovery for the Post-COVID Pulmonary Syndrome,"COVID-19 has infected over 135 million and killed over 3 million people worldwide. In Canada, over one million individuals have been infected by the virus and 24,000 have succumbed to the disease. Even in survivors of COVID-19, many are left with long-term disability and symptoms, which is now referred to as the ""post-covid syndrome"". Although the data are still scarce, it is thought that approximately 10% of COVID-19 survivors develop a post-covid syndrome, which is frequently characterized by symptoms of fatigue, headache, breathlessness, and loss of smell beyond 12 weeks post-infection. The mechanisms driving post-covid syndrome are largely unknown. However, recent studies indicate that the common risk factors for post-covid syndrome are: 1) increasing age; 2) increased body mass index; 3) female sex; and 4) lung comorbidities. The largest study of its kind to date indicates that the most common co-morbidity in this syndrome is asthma, followed by ""lung disease"" (other than asthma). Together, pulmonary disorders (asthma and ""lung disease"") were found in one-third of all those who experienced the post-covid syndrome. In contrast, only 5% had heart disease or diabetes and less than 1% had kidney disease. These data suggest that airway diseases are the leading predisposing factor for post-covid syndrome (Sudre et al Nat Med 2021). Here, we will investigate the mechanisms behind this observation. Our hypothesis is that SARS-CoV2 infection in individuals with airways disease such as asthma or COPD results in inflammatory responses that damage the airway, leading to persistent long covid symptoms in susceptible individuals. We will investigate this hypothesis by evaluating imaging and genomic changes in the airways of COVID survivors and determine whether these changes are associated with the post-covid syndrome. These results will lead to novel biomarkers to predict and diagnose post-covid syndrome.",2021,2022,University of British Columbia,398601,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C13806,177741,Muticentre Assessment of Cardiovascular Hemodynamics and Autonomic Dysfunction with Long COVID,"The COVID-19 pandemic has had a devastating impact on Canada and worldwide. There are numerous reports of patients suffering from ongoing chronic symptoms, even several months after resolution of the acute illness. These ongoing symptoms have been termed ""Long-COVID"". Common symptoms among these patients includes exertional dyspnea, fatigue, exercise intolerance, lightheadedness, and tachycardia/palpitation. Long-COVID seems to resemble chronic orthostatic intolerance (COI), in which special nerves called autonomic nerves fail to normally control heart rate and blood pressure. Patients with COI have symptoms on standing such as palpitations, chest pains, dyspnea, tremulousness, and mental clouding that are relieved by lying down,. These symptoms last >3 months (like in Long-COVID) and many start with a viral-like illness. Some specific COI disorders include Postural Tachycardia Syndrome (POTS) Inappropriate Sinus Tachycardia (IST), and Orthostatic Hypotension (OH). Treatments are effective but can be different for each of the COI disorders. We do not know how often autonomic nerves work poorly in Long-COVID, whether it is more common in patients with certain symptoms, and how common the different COI disorders are in Long-COVID. In this national cross-sectional study, we seek to characterize cardiovascular autonomic nerve function in Long-COVID. In Aim#1, we will use sophisticated non-invasive tools to understand the heart rate and blood pressure regulation, symptoms and functional burden, Long-COVID patients. In Aim#2, we will determine how common are autonomic dysfunction disorders in patients with Long-COVID, and if these are associated with specific symptoms. In Aim#3, we will bring patients back at 3 months to get early signals about recovery back to normal. If we can understand the problems underlying Long-COVID across Canada, we can develop specific targeted treatments.",2021,2022,University of Calgary,221535.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences,2021 +C13807,177742,Parental presence restrictions due to COVID-19: Examining impact and priorities for neonatal care (The PRESENCE Study),"No parent wants to be separated from their baby during a time of crisis. This is especially true for parents of sick preterm infants requiring care in a neonatal intensive care unit (NICU). Yet, given the severe parental presence restrictions due to the COVID-19 pandemic response, this is the reality for many Canadian families. Many partners must leave the hospital following attendance at the birth and for some parents who must leave to care for other children at home, they are unable to return. For parents able to stay their infant, most cannot be present together. Families lack access to their usual social support systems, partners have little engagement, and usual in-person support, education, and discharge teaching have been disrupted, all associated with higher parental mental health concerns. Many infants have reduced access to life saving breastmilk, parental touch, and learning through facial interactions, with significant implications for later development. Despite the serious consequences for vulnerable infants and their families, inconsistency exists in the degree of restriction nationally, resulting in wide variation within provinces and cities. The lack of standardized approach heightens distrust in health care provision. There is an urgent need to examine the impact of parental presence restrictions on family mental and physical wellbeing, infant outcomes, and healthcare provider experiences to identify priority areas for practice change to reduce unintended harm and inequities, as well as to inform the priority needs of families and stakeholders in the post COVID-19 period to determine a consistent evidenced based national approach. Our diverse team, including families, neonatal care providers, researchers and decision makers, are uniquely positioned to act now. We will leverage existing work and longstanding successful networks to ensure diverse engagement, rapid deployment, and broad impactful and timely uptake of our findings to improve care.",2021,2022,Dalhousie University,154093.8,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Unspecified,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C13808,177743,Evaluation of the effectiveness of probiotics on post-COVID-19 conditions.,"Google translate: The COVID-19 pandemic has affected more than 138 million people and while vaccination brings great hope, many questions remain (eg impact of variants of the virus). Studies show that patients could present symptoms up to 6 months after the acute phase (fatigue, anxiety ...). Little is known about the causes of long-lasting COVID (LONG-COV) but could be linked to persistence of the virus or inadequate immune response. Our group proposes to study the impact of the intestinal microbiota (intestinal flora) on LONG-VOC. We know that: 1) people who have a severe form of COVID-19 (elderly people, diabetics ...) often have an imbalance of the intestinal microbiota, 2) COVID-19 modifies the microbiota (ex: taking of antibiotics) and 3) probiotics can improve the balance of the microbiota. We hypothesize that LONG-COV is associated with the consequences of gut microbiota imbalance and that it is possible to reduce the occurrence of LONG-COV using probiotics. As the gut microbiota is closely related to the lungs and brain, the action of probiotics could also reach other organs affected by LONG-VOC. We propose a study which compares the taking of probiotics to that of a placebo. We will include 618 men and women aged 18 and over, symptomatic of COVID-19 with a COVID + test for 10 days or less. Hospitalized patients (population at risk of LONG-VOC) may be included if they returned home within 10 days of diagnosis. The signs of the LONG-COV will be studied on the 30th and 90th day (internet or telephone). A group of volunteer patients will take samples (saliva and stool) for virus and microbiota analyzes. If successful, probiotics could be used very quickly across Canada (few side effects, affordable costs).]",2021,2022,Université de Sherbrooke,795823.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Post acute and long term health consequences | Prophylactic use of treatments,2021 +C13809,177744,"Investigating Neuropsychological Consequences of COVID-19 on Adults, and Examination of Associated Risk and Resilience Factors","Emerging evidence suggests the virus causing COVID-19 invades the brain, raising concern over possible long-term impacts of infection (i.e.,""long-covid""), not only on brain function, but also on the integrity of the brain's capacity for thinking and supporting everyday functioning. We aim to characterize cognitive functioning in individuals who tested positive for COVID-19 (3 months following their recovery from acute symptoms), and to identify resilience/protective factors as well as risk factors that may predict cognitive outcomes. Adults who have tested positive for COVID-19 at least 3 months prior, and those with no evidence of having had the virus will complete a battery of cognitive and psychological tests via established, reliable, and valid videoconferencing techniques that are re-merging now but which have a long-standing tradition in remote assessment settings (e.g., international/cross border assessments, testing of patients in rural areas and Indigenous territories). We will compare test performance to determine group differences in cognitive functioning and other factors. We will then evaluate if one or more neuropsychological profiles (clusters) emerge from the data, characterizing COVID-19 positive patients uniquely, and then we will determine if risk or protective factors predict cluster/profile membership. Findings will inform clinicians (e.g., neurologists, neuropsychologists, rehabilitation specialists), on how to optimally develop and deploy services in Ontario and BC, and will have relevance to other jurisdictions in Canada, as well as international health care communities. Results of this study will help to ensure that any lasting secondary impacts of COVID-19 infection are appropriately and expeditiously addressed, so that those who have been affected by this virus are able to most efficiently resume complex daily activities requiring considerable cognitive effort, including employment and academic pursuits.",2021,2022,University of Victoria,158898.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C13810,177745,Long COVID-19 on the human brain,"Over one million Canadians have been infected by COVID-19. Many people who have been infected by COVID-19 experience negative mental symptoms, such as ""brain fog"" and fatigue. For many of these people, they continue to feel these negative mental symptoms even after recovering from COVID-19. However, scientists still do not know how COVID-19 harms the human brain and causes these mental problems. Our goal is to use advanced brain imaging to determine whether people who have been infected with COVID-19 show damage in their brain. We hope that this information will help doctors determine what treatments should be provided to help people who are suffering from continuing mental problems after being infected with COVID-19.",2021,2022,Centre for Addiction and Mental Health/Centre de toxicomanie et de santé mentale,744115.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C13811,177746,Living with long-COVID. Patient experience to inform policy makers and care providers,"This project aims to gather and share stories from those known as the 'long haulers', who have lived experience of the longer-term effects of COVID-19. We will work with our patient partners across Canada and research partners in Ontario, Quebec, and Nova Scotia to conduct virtual interviews, using audio/video recording, with about 50 patients from across Canada. The findings will provide an understanding of how they coped, the impact on their day to day lives, their interactions with the healthcare system, and their needs for information and support. Our project team includes scientists, patients, clinicians, decision makers, and community partners. We will build upon our pilot study of patient experience of COVID-19 in progress involving participants from Ontario and Quebec that includes a small sub-set of long-COVID patients. We are organized and equipped to incorporate diversity and inclusion of voices across gender, culture and racialized groups, age, a mix of settings, and severity of illness. Early results will be presented in a short film highlighting key themes, followed by a collection of online resources for patients and professionals, and a roundtable with patients, clinicians and decision makers to review findings and articulate key attributes of responsive, patient-oriented care for Canadians with long-COVID. We will build from existing frameworks, evidence and guidance from other jurisdictions. We are seeking a range and diversity of views to help identify the structures and processes required to address the clinical and psychosocial needs of patients, and help to rethink the health system response. Our team has a strong track record in illness experiences research and patient engagement (www.healthexperiences.ca); we collaborate with parallel projects (separately funded) on patient experiences of COVID-19 in other countries (UK, US, Netherlands, Germany, Japan, Australia, Brazil, and Spain) using the same approach (www.dipexinternational.org).",2021,2022,University of Toronto,220223.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Post acute and long term health consequences,2021 +C13812,177747,Identifying host molecular endotypes associated with diverse COVID-19 outcomes and new variants in a longitudinal multiomics cohort study of 1000 patients,"The COVID-19 pandemic has had a huge impact on people's lives all over the world. As of April 2021, more than 130 million people have been infected with the virus and over 2.8 million have lost their lives because of COVID-19 globally (data from the Johns Hopkins University Coronavirus Resource Center, accessed on April 1, 2021). While vaccination is underway in most well-resourced countries, the virus is not expected to be eradicated in the short to medium term. Understanding the diverse short- and long-term outcomes of COVID-19 remains important. For example, it is currently not possible to predict who will become long-haulers and continue to experience symptoms that last for weeks or even months. The goal of this project is to better understand the molecular underpinnings of diverse patient outcomes in COVID-19 and develop molecular diagnostics that can identify specific patient groups for targeted management (e.g., those likely to require oxygen support or at greater risk of developing long-COVID-19). Early identification of such patients would improve patient care, allow for better allocation of scarce resources to those who need them most, and may even result in the development of novel, more-personalized, treatments. We are uniquely positioned to address this thanks to existing access to the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study. IMPACC is a unique resource that includes comprehensive molecular profiling at many timepoints during infection (enrollment, days 4, 7, 14, 21, 28 post-COVID-19 diagnosis), as well as in long-term follow-up (months 3, 6, 9, and 12), on a large group (n = 1,223) of COVID-19 patients. Crucially, the size of this cohort allows for capture of disease variability driven by emerging variants, as well as the effect of vaccines in diminishing disease. The molecular signatures we develop will be validated using ongoing Canadian research cohorts.",2021,2022,University of British Columbia,367415.16,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C13813,177748,A cell-based assay to measure immune competence in SARS-CoV-2 infection and vaccination,"One of most challenging aspects of COVID-19 is the heterogeneity in the disease severity. While most patients will suffer from a relatively mild flu-like episode, a minority will experience a life-threatening or long-term disease. Being able to better understand why and who will have serious versus mild COVID-19 would improve the prediction of risk associated with COVID, the public health planning and the clinical care of the patients. A clinical tool that measures immune competence could achieve this goal. Over the last years we developed an assay based on live peripheral blood cells (monocytes and B cells) to help predict who, among transplant recipients, are more likely to suffer from severe infections. To measure the ability of the immune system to respond to a foreign aggression, we cultured these cells with peptides of the Epstein-Barr virus and assessed their response by flow cytometry. This sequential, two-step assay was developed based on extensive preliminary studies in cohorts of kidney recipients. We have completed and reported a first round of validation of the assay and we are currently performing a second, multicenter international, validation. Combined, the two steps of the assay seem to predict the risk of infection with a high predictive value in immunosuppressed patients. Here we want to assess the capacity of this assay to predict disease severity of COVID-19 in the general population. Because severe COVID is an inflammatory condition that occurs in patients who fail to clear the virus early, there is a strong rationale to believe that the 'immuno-meter' that we developed will be informative with this regard. We also want to investigate whether the result of the assay can predict how well immunosuppressed patients respond to SARS-CoV-2 vaccination. On the long run, the assay could prove to be useful not only in the transplant setting or in the COVID-19 setting, but also in the prediction of the response to other infections and other vaccines.",2021,2022,Université Laval,196438.87,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation","Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Characterisation of vaccine-induced immunity",2021 +C13814,177749,A double blind randomized trial of low-dose naltrexone for post-covid fatigue syndrome,"This study aims to determine whether low-dose naltrexone (LDN) improves energy and reduces fatigue and pain in people who had COVID-19 (i.e. confirmed SARS-COV-2 positive) and have persistent symptoms of fatigue post-viral infection (PVI). Low-dose naltrexone (LDN) refers to naltrexone given in doses of 1-4.5 mg. Naltrexone is a medication that has been used in the treatment of excessive alcohol and opioids and for some types of itchiness. It has also been used, in low doses, for the relief of symptoms related to fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The medication works differently when used in low doses compared to in high doses. Previous studies in people with FM found a significantly greater reduction in pain among those taking LDN compared to those taking placebo. Overall, the studies found that LDN is safe, well-tolerated, may reduce inflammation, and improves general health and psychological well-being. The proposed trial will be conducted at the Complex Chronic Diseases Program (CCDP), the provincial reference centre for treating ME/CFS and FM in British Columbia. The CCDP clinic has extensive experience in treating cases of FM and ME/CFS with LDN. We propose a placebo-controlled double-blind trial using LDN to treat patients with persistent symptoms of fatigue following SARS-COV-2 infection. We will find out whether people taking the medication show a reduction in symptom severity, such as sustained fatigue and pain, and improved quality of life. Individuals referred to as 'Long-haulers' or 'Long-COVID' currently do not have well researched drug interventions to treat their fatigue and related symptoms. The proposed study will demonstrate whether LDN is a medication that could benefit a large number of people with post-covid-19 fatigue illness. Furthermore, if this trial proves successful, it would lend support for further studies exploring LDN in other forms of post-viral fatigue, ME/CFS and FM populations.",2021,2022,B.C. Women's Hospital,592380.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Post acute and long term health consequences | Prophylactic use of treatments | Clinical trial (unspecified trial phase),2021 +C13815,177750,An intervention to teach self-management skills for persisting symptoms of COVID-19: Minimizing impact of symptoms on everyday functioning and on healthcare usage/utilization - A randomized controlled trial,"After a COVID-19 infection, more than 75% of patients report ongoing symptoms. Even in young people who are otherwise healthy and physically fit, these ongoing symptoms can develop and persist. These symptoms are concerning, because they can lower quality of life and stop people from returning to work. The symptoms themselves can be grouped into three types: (1) ""somatic"", including fatigue, headache, sleep issues, and respiratory/breathing problems, (2) ""cognitive"", such as symptoms of ""brain fog"" that make it harder to maintain attention or remember important information, and (3) ""psychiatric"", such as depression and anxiety (which can have a negative impact on mood). Making the effects of symptoms even more consequential is the ""vicious circle"" that often occurs, whereby one symptom exacerbates another. For example, if after COVID-19 patients have trouble falling asleep, this can then lead to mood-related problems, which can worsen brain fog. At this time, we need research to help develop treatments that limit the impact of these symptoms on people who have had COVID-19. Our intervention will provide people with increased knowledge and skills about how to manage symptoms, reducing the negative impact of symptoms on people's everyday lives. It may also help to reduce how often people must visit the doctor or go to the hospital, at a time when our healthcare system is already under extreme pressure. Our early research has shown that group-based education, which we deliver over the internet using videoconferencing, is of benefit. What we need to learn now, through a bigger study that involves more patients, is how effective this education is compared to simply having social support. This is the goal of our study, and it can help us fight COVID-19 by reducing the impact of its enduring symptoms.",2021,2022,University Health Network,263788.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C13816,177751,Identification of microbial factors to modulate immune dysregulation and treat post-COVID-19 syndrome.,"Post-COVID-19 syndrome represents a new epidemic within the pandemic, affecting potentially more than 330,000 Canadians. While several studies have described post-COVID-19 symptoms, no studies to date have demonstrated the pathophysiological mechanisms underlying these alarming sequelae. Yet, it is precisely this knowledge that will inform post-COVID-19 management and health care resource planning. Previous studies have demonstrated that the composition of the intestinal microbiota in patients with acute COVID-19 is concordant with disease severity and markers of inflammation and tissue damage. Studies in other viral infections such as HIV, have demonstrated that perturbations of the intestinal microbiota and translocation of intestinal bacteria into blood circulation contribute to inflammation and end-organ damage. We hypothesize that perturbations of the intestinal microbiota caused by COVID-19 infection persist for months following infection, leading to leaky gut and bacterial translocation, which results in persistent inflammation and post-COVID-19 manifestations. We have established the first post-COVID-19 research clinic in Montreal and will therefore synergize with our existing infrastructure to address our hypothesis. Through the study of patients with post-COVID-19 syndrome, patients with resolved COVID-19 and patients who tested negative for COVID-19 we will: 1) define the composition and function of the intestinal microbiota; 2) determine if patients with post-COVID-19 syndrome have a leaky gut by evaluating bacterial translocation from the gut into systemic circulation; 3) determine if patients with post-COVID-19 syndrome have increased systemic inflammation and immune dysregulation. This important study will help uncover a mechanism for post-COVID-19 syndrome, while identifying diagnostic markers and bringing forward new therapies such as probiotics or microbially-derived metabolites as a means to treat this debilitating syndrome.",2021,2022,Institut de recherches cliniques de Montréal,394176.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C13817,177752,SARS-CoV-2 triggers Autoimmunity: implications for the pathogenesis of Post-Acute COVID-19 Syndrome - (AI-PACS),"The coronavirus pandemic has severely affected healthcare systems and changed life as we know it, globally. In Canada alone, more than 1 million cases and >23000 deaths have been documented. Apart from the acute phase disease complications, it is now apparent that a significant proportion (15%) of patients who recover continue experiencing symptoms such as chronic fatigue, shortness of breath, joint pains, cognitive impairment (""brain fog""), etc for several months, if not for life. This syndrome has been labeled as ""long-COVID"" or Post-Acute COVID-19 Syndrome (PACS) and can happen to anyone whether you're young, old, healthy, or have a chronic illness. One can get it even if the COVID-19 symptoms were mild. There is no confirmed cause as to why this happens. However, there is data to support that inappropriate activation of the immune system by the virus may play a role. While our immune system is programmed to protect us against foreign invaders (such as viruses), in this case, it is directed against elements of our own. The net result is autoimmunity, where the immune system produces autoantibodies that cause damage to the body. This may lead to the development of chronic and serious diseases like lupus, rheumatoid arthritis, vasculitis, scleroderma, and others. Our preliminary data show that more than half of patients post-recovery develop multiple autoantibodies. That said, it is not known if these patients will develop autoimmune diseases in the future. The aim of our study is to understand the exact impairment of the immune system, why these patients develop autoantibodies, characterize their impact on the clinical symptoms of PACS, and, potentially, identify ways to modify this. The study's impact is significant since it is projected that 100000 Canadians will experience (or are already experiencing) this syndrome. Our team brings together several experts, both clinicians, and scientists, to guarantee the success of the project.",2021,2022,McMaster University,398397.51,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2021 +C13818,177753,"Long COVID and Episodic Disability: Advancing the Conceptualization, Measurement and Knowledge of Episodic Disability with people living with Long COVID","Our goal is to characterize the disability experiences among people living with Long COVID in Canada, UK, United States, and Ireland; and to develop and assess the properties of a patient-reported outcome measure (PROM) to assess the presence, severity and episodic nature of disability among people living with Long COVID. Standardized PROMs that capture disability and its fluctuation over time are critical to guide timely and appropriate Long COVID care. In earlier work, we developed and validated the Episodic Disability (ED) Framework in the context of HIV, and established a PROM to capture episodic disability across 6 domains: physical, cognitive, mental-emotional health, daily activities, uncertainty about the future, and social inclusion. This tool possesses reliability and validity among adults living with HIV internationally. As the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. The multidimensional and fluctuating nature of Long COVID may be similar to other episodic illnesses such as HIV, highlighting an opportunity to apply lessons learned in the context of Long COVID. In Phase 1 of this study, we will conduct a series of interviews to explore experiences of disability (dimensions, influencing factors, triggers) and extent to which the ED Framework applies to living with Long COVID. In Phase 2, we will establish an Episodic Disability Questionnaire and assess its measurement properties for use with Long COVID. This study builds on our work in episodic disability among an international team with expertise in episodic illness, measurement, COVID-19, and rehabilitation. Findings will yield the first known conceptual framework and PROM developed to assess the prevalence and impact of episodic disability in Long COVID. Future universal measurement of disability may assist with clinical management, tracking of episodic disability trends, and evaluating interventions for people living with Long COVID.",2021,2022,University of Toronto,162955.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C14292,,Antibody correlates of vaccine-induced immunity to SARS-CoV-2 501Y.V2,,2021,-99,N/A,68502,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity, +C14293,,Examining the duration of antibody responses for SARS-CoV-2,,2021,-99,N/A,272868.75,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics",Immunity, +C14294,,"Nitazoxanide for mild to moderate COVID-19 in HIV-infected and HIV uninfected adults with enhanced risk: a double-blind, randomized, placebo-controlled trial in a resource-poor setting (Catalysing the Containment of COVID-19; the C3-RCT)",,2021,-99,N/A,1049937,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other | Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase) | Prophylactic use of treatments, +C14295,,Development of an Autologous Human Dendritic Cell Vaccine to Treat SARS-COV-2 501Y.V2: A Preclinical Trial,,2021,-99,N/A,45773.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Vaccines research, development and implementation",Pre-clinical studies, +C14296,,Investigating Point of Care Diagnostic Strategies to Optimise the Rapid Diagnosis of COVID-19 in routine public and private health care settings in South Africa,,2021,-99,N/A,770000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14297,,A prospective surveillance network linking SARS-CoV-2 genomics and clinical severity data in South Africa - DATCOV-Gen,,2021,-99,N/A,139995.31,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis", +C14298,,Surveillance for SARS-CoV-2 in South Africa,,2021,-99,N/A,561554.56,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,Epidemiological studies,Disease transmission dynamics, +C14299,,Assessing the clinical severity of the SARS-CoV-2 variant 501Y.v2 vs previous variants/lineages,,2021,-99,N/A,27559.77,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis", +C14300,,A linked database (registry) of COVID-19 related deaths,,2021,-99,N/A,92785,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,Data Management and Data Sharing,,,,South Africa,Health Systems Research,Health information systems, +C14301,,"A proposal to ignite civil society engagement around key COVID-19 issues, mobilise national community ownership of COVID-19 research and address anti-science, anti-research trends on social media",,2021,-99,N/A,209876.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Policies for public health, disease control & community resilience",Community engagement | Communication, +C14302,,Structural characterization of 501Y.V2 enhanced transmissibility,,2021,-99,N/A,81200,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C14303,,Infectiousness of the 501Y.V2 variant using aerosol sampling technology,,2021,-99,N/A,137998,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Environmental stability of pathogen | Disease transmission dynamics", +C14304,,Defining SARS-CoV-2 neutralizing responses and Fc effector function in COVID-19 acute and convalescent sera in South Africa,,2021,-99,N/A,367172.47,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,South Africa Department of Science and Innovation | South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Pathogen: natural history, transmission and diagnostics",Immunity, +C14305,,"An adaptive phase I/II randomized placebo-controlled trial to determine safety, immunogenicity and efficacy of non-replicating ChAdOx1 SARS-CoV-2 vaccine in South African adults living without HIV; and safety and immunogenicity in adults living with HIV",,2021,-99,N/A,700000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,South Africa Department of Science and Innovation | South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial, +C14306,,Maternal and perinatal outcomes of pandemic influenza or novel coronavirus in pregnancy,,2021,-99,N/A,84000,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),,Pregnant women | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Pandemic-prone influenza,South Africa Department of Science and Innovation | South African Medical Research Council (SAMRC),South Africa,Africa,,Africa,,,,,South Africa,Clinical characterisation and management,Disease pathogenesis, +C14307,AH/V008560/1,Understanding the Impact of COVID-19 on Modern Slavery in Global Garment Supply Chains,"Amidst COVID-19, garment supply chains feeding the United Kingdom markets have changed dramatically. As demand for new clothes has plummeted amidst government-imposed lockdowns, brand companies have cancelled orders and refused to pay for goods already produced, leaving suppliers unable to pay wages. As garment producing countries prepare to face intermediate challenges, including reduced order volumes and brand requests for discounts, governments have suspended minimum wages for garment workers, businesses have laid off unionised workers. As garment workers compete for relatively little work, there is widespread concern among civil society, United Nations organisations, and others that these dynamics will fuel and exacerbate business demand for forced labour within the global garment supply chain, while lowering workers' bargaining power for decent work conditions. This project will undertake a multi-country comparative study to determine whether, how, and with what consequences COVID-19 is deepening vulnerability to forced labour in garment-producing countries. It will use an innovative mixed-methods approach including: supply chain mapping; a multi-country digital survey of workers and suppliers; in-depth interviews with workers, business representatives, trade unionists, and government officials; and analysis of Bank of England Covid Corporate Financing Facility data. Drawing on research methods successfully pioneered through my previous research, this project will generate urgent, ground-level data to deepen understandings of the impact of COVID-19 on those vulnerable to forced labour and efforts to detect and prevent it. The project will put vulnerable workers at the heart of the research with the aim of helping them to influence corporate practices and government policy.",2021,2021,University of Sheffield,164019.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C14308,AH/V008676/1,Tackling Modern Slavery in Malaysian Medical Gloves Factories Using a Whole-Systems Approach to the Supply Chain,"This project will identify and implement mechanisms to prevent and remediate modern slavery in the recruitment and employment of workers in the medical gloves sector in Malaysia, where demand for gloves has more than doubled during the COVID-19 pandemic, whilst endemic abuse of worker rights has either continued or become worse. In 2019 Malaysia was the source of two-thirds of gloves supplied to the world by volume, and also the main source of gloves to the UK's National Health Service (NHS). Over 1.8 billion gloves have been provided for use in health and social care in England since the start of the pandemic. Manufacturing is reliant on migrant labour in glove factories, where recent media reports highlight conditions of modern slavery, including payment of high recruitment fees leading to debt bondage, confiscation of passports, and restrictions on movement or association. The UK NHS Supply Chain is the single largest purchaser of gloves in the world, responsible for procuring up to 80% of medical goods in England and Wales. The recent UK Government Modern Slavery Statement in March 2020 included a commitment to pilot work in the gloves sector which, along with increasing pressure on the production of gloves, means it is timely to pick up analysis and identify where in UK and international supply chains change can be leveraged, and understand the drivers and barriers to such change. The research will employ a whole-systems approach to understand structures and processes affecting workers and modern slavery in the Malaysian gloves sector during the pandemic. Through interviews with actors at all tiers in the supply chain (workers, factory management, suppliers, purchasers, and policy makers), we aim to identify pathways of change and communicate these throughout the supply chain so that, for example, procurement policy can be made sensitive to the realities of global supply chain issues, including providing appropriate logistical support, commercial and contractual terms, and pricing to enable the changes needed, and incorporating mechanisms to enable real and sustained worker voice and representation. Our approach to understanding and tackling modern slavery in Malaysian medical gloves factories involves the use of a whole supply chain approach to avoid a situation where individual subsystems are optimised but the whole supply chain remains sub-optimal. Through stakeholder engagement workshops, reports and policy briefs, the project will generate policy influence and change focused on UK procurement and supply chain organisations in the UK and Malaysia and will build the connection between procurement governance and practices in the UK and the occurrence of labour exploitation at the upstream end of the supply chain in Malaysia. Most importantly, it will support demonstrable outcomes for the victims and survivors of modern slavery in the Malaysian gloves sector, including education and the reimbursement of recruitment fees, and will produce recommendations for policy-makers and NHS procurement on incentivising and implementing improvement. The project will be executed by an interdisciplinary team already at the forefront of raising awareness and tackling these issues in the gloves supply chain, in order to ensure swift and sustainable positive outcomes.",2021,2021,Newcastle University,162540.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Western Pacific,Western Pacific,,,,Malaysia,Malaysia,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C14309,AH/W003643/1,Co-design and implement a COVID-19 vaccine uptake intervention within Chinese communities in England,"This study addresses the call of the UK Government Scientific Advisory Group for Emergencies (SAGE) (2020a) by investigating complex and multi-layered factors and determinants of Chinese communities' vaccine hesitancy, as well as the barriers and facilitators of vaccination uptake. Through focus groups (up to 16 groups), interviews (up to 20) and surveys (up to 1,000) with members of the Chinese communities and community workers, this study will address gaps in knowledge by exploring the understanding, attitude, risk perceptions, trust, source of information, barriers, facilitators, and concerns of the communities. The central aim of the study is to use the above empirical data to inform the co-design/development and implementation/evaluation of a communicative intervention to promote the uptake of COVID-19 vaccines with the Chinese communities. The study will then explore the opportunities to scale up its impact in other cities in England where there are large Chinese populations. It will also explore the possibility of adapting the resources developed from this study for other ethnic communities in collaboration with the Centre for Black and Minority Ethnic (BME) Health which has well-established connections with Black, Asian, Ethnic Minorities (BAME) communities. Core digital resources (app codes, databases) and content (radio jingle, animation story board, leaflets) will be produced as templates and made publicly available for cultural adaptation for other ethnic community organisations. The project will produce reports with advice, guidance and best practices for community organisations, the NHS Clinical Commission Groups (CCGs) and policy makers (e.g. Sage ethnicity subgroup) and a standard scholarly publication.",2021,2021,University of Leicester,82531.84,Human Populations,Asian | Black | Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C14310,AH/W003694/1,"UK Literary Heritage Sites and Covid-19: measuring impact, enhancing resilience, and learning lessons.","Across the UK there are around 70 museums in writers' homes and birthplaces open to the public. Some are world famous, attracting big annual footfall; some are run on a shoestring by small groups of volunteers. All will have been profoundly impacted by Covid-19, in ways unique to the sector. Most will have tried to develop new ways of engaging with the public during lockdown and the subsequent restrictions. The impact of the pandemic and the responses to it remain unknown, unquantified, and unanalysed. The UK's literary heritage sites include museums dedicated to globally renowned household names such as Shakespeare, Dickens, Austen, and Burns, as well as to underappreciated national treasures such as Laurence Sterne, Elizabeth Gaskell, and Horace Walpole. The challenges faced by the literary heritage sector during Covid-19 are different from those faced by other museums, stately homes, and heritage sites, and there is reason to believe that the sector has been hit particularly badly by Covid-19 issues, with several key sites ineligible for or unsuccessful in securing financial support from government. Above all, the study will seek to identify and quantify the challenges posed to UK literary heritage sites by Covid-19, to evaluate and compare responses between sites, and to help this world-class sector develop its future resilience.",2021,2022,University of Huddersfield,61045.76,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C14311,AH/W003813/1,Between environmental concerns and compliance: How does media messaging affect motivation and choice between disposable versus reusable facemasks?,"Facemasks are a crucial part of UK strategy to contain and mitigate transmission of COVID-19. While disposable facemasks present a convenient, low-cost solution, they carry greater associated environmental costs than reusable masks which are less likely to be discarded but require higher financial outlay. Although clearly central, the influence of media messaging - positive or negative - in determining people's mask-wearing choices is unknown, despite the considerable medical and environmental implications. This project will explore the complex factors underpinning consumer choice of masks and the adoption or rejection of facemask wearing, including responsible disposal of masks, by using multi-disciplinary methods to evaluate constructive and destructive messaging around (a) mask-wearing and motivation, and (b) sustainable choices within the facemask wearing arena. There are three components: 1. Assessing the influence and effectiveness of media messaging around the wearing of facemasks to date. 2. Examining the ways in which more effective media messaging can be developed to respond to rising rates of infection as well as potential long-term facemask use in the post-Covid era. 3. Examining how the wearing of facemasks can be encouraged in an environmentally friendly and sustainable manner to prevent short, medium and long-term collateral environmental harm, in alignment with the UK's obligations under international human rights and environmental laws. The overarching aim of this twelve-month project is, then, to better understand current facemask wearing behaviour as influenced by the media to improve uptake and enhance the effectiveness of media campaigns for the future, specifically considering environmental issues.",2021,2022,Bangor University,440286.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2021 +C14312,AH/W003945/1,"Children, acceptable health risks and COVID-19: Ethical guidance for a fair policy response","To respond to the pandemic the NHS deployed strategies (e.g. usual service restriction, changes in care delivery, redeployment of staff and clinic space) which had an immediate effect on children's usual care. To date, the direct impact of Covid-19 infection on children's physical health has been recorded as being far milder than for other groups. By contrast the indirect impact on children has been profound, with substantial reductions in urgent activity in hospitals (von Dadelszen, Khalil, Wolfe et al. 2020 BMJ). There are no known studies which assess the extent to which health service restrictions and changes in care delivery are fair for children. This project, undertaken in collaboration with NHS child healthcare specialists, aims to address the omission of a children-related ethical dimension in Covid-19 related research and policy. It will achieve this by exploring which risks on children's physical and mental health can be morally justified in health systems' response to the pandemic. This project will provide accessible ethical guidance to medical authorities and government departments on how the needs of children with long-term conditions should feature in the prioritisation process required in the pandemic context. This guidance will be assessed, in context, in conjunction with a range of decision-makers who are responsible for making decisions about the allocation to resources and by working closely with the clinical-academic Children and Young People's Health Partnership (CYPHP) in South East London.",2021,2022,University of Oxford,290469.12,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Clinical and Health System Decision-Making | Communication,2021 +C14313,AH/W00416X/1,Re-Inventing the Live Arts Event with Local Arts Communities: Covid 19,"Has Covid-19 killed the live event? Many in the Creative Industries fear so. An alternative view, however, could be: 'Long live the live event!' The proposed research will interrogate this dynamic by exploring how artists can re-invent the live event by asking the following questions: How do pandemic-related changes to conditions of production affect art-making for live events? What are the creative solutions explored by artists across genres to re-invent live events (e.g. site-specific, multi-media, participatory) under Covid-19 restrictions? How do Covid-19 restrictions affect the intrinsic power of live events to generate a sense of community and enable shared experiences? How do audiences respond to innovative live arts events, which might appear experimental and unfamiliar to them? How does the pandemic change people's understanding and appreciation of live arts events? How can pandemic-related changes be harnessed to improve future resilience in the creative sector? In order to explore these questions, the PI will organise a local arts festival in North Wales (June 2021), bringing together artists and performers with the shared aim of creating a series of live outdoor and indoor events. The PI will shadow, document and discuss the artistic work-in-progress and the art works during the preparations for the festival as well as after the festival. Collaborating artists will document their work-in-progress and discuss their work with academics and stakeholders in an online conference. The PI will collaborate with artists on a co-authored article, making the research findings available to key stakeholders and informing future practice. All aspects of the research project will be available online.",2021,2022,Bangor University,85025.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C14314,BB/W003546/1,The risk of SARS-2 establishing itself in animal reservoirs,"The current SARS-2 pandemic is primarily driven by human to human spread, yet its origins began in wildlife and the virus displays a propensity for repeated spill over from humans to other animal species. The establishment of infection spreading from animal to animal in farmed mink in Europe has highlighted that the virus is quite capable of establishing itself in new animal reservoirs. Should the species it establishes in be a wild animal rather than an easily culled domestic one this creates a permanent re-infection risk for the human population, greatly complicating efforts to minimise COVID-19s impact Southern India is a prime hotspot for zoonotic spillovers with a dense human population and a tropical climate with high species diversity and density in the animal population. Ample opportunity exists for human/wildlife interactions and the sharing of pathogens. This project will focus on identifying whether SARS-2 spill over is occurring into the wild animal population in the Indian State of Kerala. The project will use established pan-coronavirus PCR and deep sequencing methods used successfully to identify coronaviruses in wild animals to determine whether animals in this location are contracting SARS-2 from the human population and whether it is establishing independent circulation. This project will in addition identify any other coronaviruses present filling a crucial knowledge gap in preparation for the next pandemic. The sheer variety of wildlife present in Kerala means that it is not feasible to sample all species, this project will focus on those groups (bats and small carnivores) with a known propensity for SARS-2 infection , those likely to carry SARs like viruses (the sarbecovirus genus) naturally and those in close contact with the human population",2021,2022,University of Nottingham,112212.48,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,South-East Asia,South-East Asia,,,,India,India,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +C14315,BB/W003562/1,Rapid Molecular Diagnostics For New&Emerging SARS-CoV-2 Variants of Concern-Protecting Vaccine Efficacy,"Despite the successful development of several efficacious vaccines, the COVID-19 pandemic continues to threaten the UK and global populations. Whilst vaccinations efforts have been hugely successful and provide the basis to facilitate opening up of society and a return to normality, the emergence of SARS-CoV-2 variants capable of evading the immune response endanger the efficacy of the vaccination strategy. To preserve the efficacy of SARS-CoV-2 vaccination in the UK population, aggressive and rapid surveillance for known and emerging SARS-CoV-2 variants of concern (VoCs) is required. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response to facilitate containment. In this project, we expand our recently developed SARS-CoV-2 variant-specific detection technology to allow rapid discrimination of variants of concern. This approach can be implemented directly and immediately on positive samples in the pipelines of large testing facilities or developed for Point of Care (PoC) use. This technology will complement the current genomic sequencing efforts that allow identification of new and existing VoCs and facilitate lineage tracking, with rapid molecular diagnostics able to assist the public health response by identifying key variants without the delay and sub-sampling associated with genomic sequencing, therefore allowing a rapid and agile response to aid breaking chains of transmission and facilitate containment before widespread community transmission occurs.",2021,2021,Cardiff University,103020.8,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2021 +C14316,BB/W00402X/1,Global trade of coronavirus hosts: bringing geographically isolated hosts and viruses together risks novel recombination and spillover to humans,"Novel pathogenic coronaviruses - such as SARS-CoV and probably SARS-CoV-2 - arise by two coronaviruses co-infecting viruses a single host cell, and then 'swapping' parts of their genome. The result of this swapping (termed homologous recombination) is a novel daughter virus containing components of each parent virus. These viruses then circulate in reservoir animal populations before spillover to humans. Our previous work has identified mammalian and avian hosts susceptible to each coronavirus and hosts biologically susceptible to multiple coronavirus strains (recombination hosts). Here, using a novel ecological network approach, integrating presence, habitat, and behaviour indicating ecological traits of host species, we will build on our previous work to predict contact facilitated sharing of coronaviruses. Combining these predictions with epidemiologically-relevant spatial predictors, will allow us to predict geographical hotspots of coronavirus recombination (Work package 1), and therefore enable specific spatially-targeted surveillance and mitigation efforts. Many coronavirus hosts interact with humans (e.g. through geographic/habitat overlap), or are used by humans as (e.g. pets/food). By enriching our novel network from WP1 with host species utilisation data from open-access sources, we will estimate the in situ likelihood of spillover from our previously identified hosts (Work package 2). Highlighting priority species and geographic hotspots for spillover mitigation efforts. Wild animal trade has been implicated in the spillover of coronaviruses, including SARS-CoV-2, to humans. Trade could also readily facilitate homologous recombination in otherwise geographically isolated hosts and their respective coronaviruses. Utilising global animal trade and usages in our predictive framework will enable us to assess the impact of trade on spillover and recombination risk (Work package 3). Understanding the relative risk of wild host trade will allow insight into avoidable human influence on novel coronavirus generation.",2021,2022,University of Liverpool,150279.68,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics,2021 +C14317,BB/W006839/1,SARS-Cov-2 infection at the animal-human interface: longevity and re-infection dynamics with virus evolution,"SARS-CoV-2 infection causes asymptomatic through severe clinical presentations in humans. Parameters around infection and transmission dynamics have been studied in animal models. However, there are growing reports of 'reactivation' and re-infection with variant SARS-CoV-2 viruses, months after 'recovery'. The frequency, timing, clinical and virological consequence, in terms of infectious virus shedding and onward transmission following secondary intra- and inter-species infections, remain unknown. The underlying immunological mechanisms behind these infections also remain unexplored. Additionally, SARS-CoV-2 infection in mink has generated novel virus variants, capable of infecting and partially evading existing immunity in humans, increasing the threats of re-infection. Here, we propose to use our established ferret model of SARS-CoV-2 (human and animal adapted viruses), to study longitudinal outcomes of respiratory droplet infection for two genetically different viruses over a six-month period. We will monitor virological and immunological progression of longitudinal SARS-CoV-2 infection; investigate the consequences of SARS-CoV-2 re-infection with homologous and heterologous strains; and investigate the effect of adaptation and immunity on the evolution of SARS-CoV-2 during these infections. We hypothesise that productive re-infection with SARS-CoV-2 variants can result in both infected and infectious stages, the latter being able to transmit disease irrespective of prior exposure and immune status. These investigations will provide detailed robust novel information relevant to mitigation strategies such as droplet avoidance, herd immunity, vaccination and virus evolution. It will also address questions regarding the emergence and maintenance of SARS-CoV-2 in animal reservoirs which may threaten eradication and long-term management of COVID",2021,2022,Animal and Plant Health Agency (APHA),611772.16,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +C14318,BB/W009501/1,What's the Risk from and to European wildlife from SARS-like Coronaviruses?,"The current COVID-19 human pandemic had its origins in SE Asian wildlife, and although the natural, endemic host remains unknown (most likely bats), onward transmission from humans to other species including large outbreaks in farmed mink and cases in domestic cats keep occuring . The outbreak in mink in Europe and the USA with transmission back to humans has raised the spectre of the virus establishing itself in other animal hosts, creating a new reservoir for the virus, with potentially serious consequences for both humans and affected animals. Europe is home to a large number of wild mustelid species, including feral mink, along with bats known to carry SARS-like viruses and cricetid rodents thought to be susceptible to SARs-CoV2. However, we currently have no idea whether any virus spill-over or circulation is occurring in these animals. This project will perform PCR based screening of faecal and lung samples from the highest risk wildlife species for SARS-CoV-2 like viruses in the UK (bats, mustelids and cricetid rodents), including retrieval of full virus sequences from any positive animals using NGS sequencing techniques (Illumina and Nanopore). The project will determine: a) If SARS-COV-2 spill-over from humans into wildlife is currently occurring b) What other coronaviruses these animals are carrying This will enable decisions to be made as to whether SARS-CoV-2 circulation in European wildlife represents a real risk to the human population and/or to wildlife, and if monitoring or mitigation programmes are necessary",2021,2022,University of Nottingham,373160.96,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +C14319,BB/W010747/1,The Molecular Basis Of The Sex-linked Functional Differences In B Cells,"The risk of mortality from Covid-19 is up to two-fold higher in men versus women, especially in the middle-age category, across different cultures and social structures. However, the biological reasons behind this difference is unknown. Recent research has highlighted significant divergences in the immune system response between the two sexes. This observation has been paralleled by the discovery of tissue-specific euchromatinisation of the inactive X chromosome in both B and T cells, accompanied by the identification of immune-related genes that specifically escape X inactivation in B cells. One of these escapees, TLR7, is a receptor for ssRNA viruses such as SARSCoV- 2. Its increased dosage caused by bi-allelic expression in women, has been shown to be advantageous for B cells response upon stimulation of TLR7. Moreover, recent studies have shown hypomorphic alleles of TLR7 lead to severe Covid-19 in young men. We hypothesised that, following escape from X inactivation, double-dosage of one or more X-encoded genes involved in B cell activation could be at the basis of the sex-linked differential mortality from Covid-19. To identify the X-encoded B-cell specific proteins that are present in higher dosage in women, we propose an unbiased approach, employing quantitative mass spectrometry from B cells from healthy, middle-aged men and women. We thus aim at identifying relevant proteins which could represent potential pharmaceutical targets to improve the prognosis of SARS-CoV-2.",2021,2022,University of Edinburgh,134216.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C14320,BB/W010763/1,Mechanisms of coronavirus replication: the role of cellular lipids in the generation of replication organelles,"Following entry into the host cell, coronaviruses, including SARS-CoV2, remodel cellular membranes to form replication organelles. A characteristic feature of this membrane remodelling is the formation of distinctive double membrane vesicles (DMVs) in which the viral RNA resides and replicates. DMV generation involves rewiring of host lipid metabolism. We found that expression of two SARS-CoV-2 proteins (nsp3C and nsp4) is sufficient to induce abundant DMV formation in human cell lines, with a corresponding upregulation of host cell lipogenic pathways that our preliminary data suggests is essential for the formation of DMVs. Replication of other viruses has been shown to depend on lipid transport from host cell organelles at sites of contact between the outer DMV membrane and that of the host organelle. We have identified extensive membrane contact sites between DMVs and a variety of host cell organelles in SARS-CoV-2 infected lung epithelial cells. In the proposed study, we aim to generate stable inducible SARS-CoV-2 nsp3C/nsp4 cell lines to use as a model of SARS-CoV-2 replication. Using this model, we will elucidate key pathways that mediate lipid provision for DMV formation, by first exploring the contribution of different cellular lipid sources. We will further establish, by expression of key candidate SARS-CoV-2 proteins and manipulation of membrane contact site machinery, how DMV-driven interorganelle lipid transport mechanisms are regulated, in order to identify novel targets for potential therapeutic intervention. Finally we will assess the effect of lipogenesis/lipid transport inhibition on DMV formation and cell survival in SARS-CoV-2 infected cells.",2021,2022,University College London,269693.44,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C14321,BB/W010771/1,Developing a rapid quality control and long-term stability assay for RNA vaccine candidates,"RNA vaccines against SARS-Cov2 have shown great promise with early results from clinical trials indicating >90% protection conferred. The RNA component of these vaccines is very long, up to 10,000 nucleotides, which introduces analytical challenges as standard methods such as gel electrophoresis are not sufficient to detect small differences in chain length. In addition, assays to detect the presence of the 5' cap that is necessary for efficient translation rely on slow and laborious methods. Thus, there is a need to develop new analytical technologies that can be applied to the QC/QA of RNA vaccines to support both manufacturing and the assessment of the long-term stability of vaccines during storage. We have previously demonstrated a proof-of-concept for a new RNA assay that is able to capture the molecule by one end and then probe specifically for the other end, leading to a measurable signal only when the RNA molecule is intact and contains a 5' cap. However, when applied to long RNA molecules such as vaccines, the assay loses sensitivity due to steric hindrance in the initial capture step. Therefore, high concentrations of RNA are required for analysis, which might limit the overall application of the assay. In this project, we aim to explore a series of interventions designed to maximise RNA capture. We will compare three strategies in the project. First, we will use statistical design of experiments to optimise our existing assay by varying the concentrations of the different molecules involved to maximise the signal-to-noise ratio. Second, we will try reversing the assay so that we capture the RNA molecule by the 5' cap and probe for the opposite end. Finally, we will examine whether it is possible to omit the capture step entirely and form a complex that bridges both ends of the RNA molecule leading to a fluorescence signal. As a proof-of-concept we will apply the assay to the Imperial College saRNA vaccine candidate that is currently undergoing clinical trials. To build on this proof-of-concept study, we aim to engage with a broad variety of stakeholders to enable uptake by vaccine manufacturers and will seek regulatory approval to enable the assay to be used for batch release testing.",2021,2023,Imperial College London,312174.08,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +C14322,BB/W010801/1,Circadian Rhythms in the light of COVID-19: Formulating optimal time-of-day regimens for antiviral drugs using human 3D models and in silico modelling,"A number of antiviral, immunomodulatory and anti-inflammatory drugs are being repurposed for COVID-19. Clinical trials worldwide are testing their use as a treatment and/or prophylactic. At present, no clinically available antiviral drugs have been established for SARS-CoV-2. We have recently prioritized promising drug candidates for COVID-19 based on in vivo pharmacokinetic drug modelling in target tissues. Moreover, a number of new animal models are being tested in SARS CoV-2 infections studies in combination with promising drug candidates. Human immune defence, inflammatory responses as well as efficacy of therapeutics and vaccines follow robust daily circadian rhythms, but their role in SARS-CoV-2 infection has yet to be studied. Moreover, recent systems-level studies have defined many host factors and physiological pathways as potential therapeutic targets, many of them which are under the circadian control. To devise therapeutic strategies to counteract SARS CoV-2 infection and the associated COVID-19 pathology, it is crucial to understand how SARS COV-2 affects the host circadian rhythms during infection, and to apply this knowledge towards improved repurposing of existing drugs and development of new drugs and drug formulations. Our interdisciplinary study aims to determine optimal time-of-day regimens for currently repurposed antiviral COVID-19 drugs and develop in silico mathematical models for their time-of-day use in vivo. This will provide time-of-day information on when such drugs exert most potent effects (on viral load and/or viral-induced inflammation) without perturbing circadian clock timing (least toxic). Disruption of circadian timing has serious consequences on many physiological processes especially given its essential role in drug metabolism and recovery from bacterial/viral infections with emerging relevance to SARS-CoV-2. This inter-disciplinary project will lead to novel understanding of how SARS-2 viral infection impacts human circadian rhythms and clock-controlled inflammatory pathways. This project will utilise cutting-edge molecular and biochemical techniques (gene/protein expression, 'omic' profiling, real-time bioluminescence imaging) to analyse cellular and organ-level circadian rhythms upon SARS CoV-2 infection using susceptible human cell types and experimental animal models as well as combined in vitro/in vivo pharmacokinetic drug modelling to project optimal times-of-administration of antiviral drugs in a human setting. This new knowledge will provide new insights on time-of-day dosing profiles of current repurposed COVID-19 drugs, which will have help guide ongoing/future clinical trials to obtain improved clinical outcomes and in vivo experimental studies. This study will also uncover novel drug targets at the interface between circadian control and SARS CoV-2 viral infection to aid development of improved drug formulations thus moving towards precision medicine based on chronotherapy for COVID-19.",2021,2023,University of Liverpool,439756.8,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2021 +C14323,EP/V027468/1,"Epidemic modelling and statistical support for policy: sub-populations, forecasting, and long-term planning","The ongoing COVID-19 epidemic requires careful monitoring as a variety of measures such as lockdown and social distancing are introduced and subsequently relaxed, leading to varying levels of demand for and capacity within the healthcare system. The disease has varying expected outcomes depending on the age, sex, and underlying comorbidities of cases. Epidemic dynamics, particularly in the presence of changing control policies, will shift the dominant modes of transmission and hence the distribution of disease. We will develop models to integrate the diverse but often noisy and incomplete datasets available, providing real-time policy support together with quantification of uncertainty. We will address three particular challenges. (1) Understanding spread in closely connected sub-populations in which there are close, repeated contacts capable of spreading disease such as households, hospitals, prisons, and care homes. Data from these contexts allow epidemiological parameters relating to infection risk conditional on contact to be identified in statistical work, and they are also important foci for policies. (2) Making short- and medium-term predictions of the epidemic trajectory and healthcare demand with appropriate uncertainty quantification. (3) Modelling long-term prospects for the epidemic, including the likelihood of eventual endemicity, the consequences of different virological assumptions about SARS-CoV-2, and how the different scenarios in this context will interact with long-term societal and health consequences of the pandemic. The project will use mathematical methodology, integrated with interdisciplinary expertise from social science, biology, clinical medicine, and epidemiology.",2021,2022,The University of Manchester,573858.56,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Post acute and long term health consequences,2020 +C14324,EP/V034502/1,GCRF_NF178 Mobile Arts for Peace (MAP) at home: online psychosocial support through the arts in Rwanda,"During COVID-19 lockdown the Rwandan government initiated strict measures to prevent movement outside the home. Restrictions due to the pandemic increased risks of gender-based violence, teenage pregnancy and school drop-out. Previous studies reported that 26.1% of the population were estimated to have symptoms related to posttraumatic stress disorder (Munyandamutsa et al. 2009); whereas recent studies have reported similar prevalence (RMHS, 2018) and genocide survivor organizations have reported an increase in mental distress during the lockdown. Deteriorating economic conditions pose a significant risk to young people's mental health, which could be further entrenched should further waves of the pandemic occur. Specifically, within Rwanda, there are no current initiatives to provide psychosocial support at home (including referral systems for those in need of more specialist intervention) or building two-way communication and synergies between formal and informal education structures (i.e. schools and community-based groups) to enable learning and social networking during social distancing. MAP at home examines the potential for providing mental health support and community engagement in Rwanda through interactive online platforms, participatory arts workshops, and communications between young people, educators, cultural artists and psychosocial workers across the five provinces of Rwanda: Rwamagana District (Eastern Province); Rubavu District (Western Province); Gicumbi District (Northern Province); Huye District (Southern Province); and Kicukiru District (Kigali Province). MAP at home will research the prevention of, response to and awareness of mental health and promotion of psychosocial well-being among youth, families, and community members through an innovative arts-based, culturally-informed approach, responsive to the needs of participants. MAP at home will generate knowledge on how to reach, engage and equip young people and caregivers with tools for psychosocial wellbeing through the development of a psychosocial module, online and participatory workshops (subject to COVID-19 guidance and social distancing measures), and integration of psychosocial workers. MAP will partner with community-based mental health provider Uyisenga Ni Imanzi, research organisation Institute of Research and Dialogue for Peace (IRDP), national cultural organisation Rwanda Arts Council, and government mental health providers Rwanda Biomedical Centre/Mental Health Division and National Rehabilitation Services to coproduce the design, implementation and dissemination of research from a local to national level. UNESCO serves as a project partner to align national to international policy implementation concerning youth policy and mental health. The project will respond to the following research questions in relation to COVID-19: *How can arts-based approaches be translated to online platforms to enhance psychosocial well-being? *What lessons can be learnt from the provision of online arts programmes for psychosocial well-being, especially regarding building resilience (individual and systemic) against future outbreaks or crises? *How might MAP at home advance digital innovation in the design and delivery of mental health provision and response services in Rwanda?",2021,2022,University of Lincoln,389422.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Rwanda,Rwanda,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C14325,EP/V034553/1,"GCRF_NF138: Uptake of Public Health Practices for Prevention of COVID-19 among Refugees, Pastoralist Communities, Truck Drivers, Slum Dwellers: Uganda","How can the uptake and acceptance of health guidelines regarding COVID-19 be improved among 'hard-to-reach' communities in Uganda, specifically among refugees, pastoralist communities, truck drivers and urban slum dwellers? Specifically, the project will consider how guidelines can be made more compatible with local cultural practices, and practical and economic constraints, and whether this indeed improves the distribution and uptake of information. Since in many communities women are central to preventive activities, the project pays specific attention to the gendered aspects of the distribution, communication and uptake of health guidelines. It further considers how trust in health organisations can be improved by means of including local community organisations in developing and implementing health guidelines. The main objectives are: 1) To establish how culture, information, attitudes and practices unique to targeted communities influence the risk of COVID-19 transmission. 2) To promote culturally sensitive radio and mobile phone communication to enhance awareness of the COVID-19 prevention; specifically, the relevance and the importance of community engagement and local solutions. 3) To examine the role of trust in health organisation with the aim to build local community capacity to respond to pandemics, and to gather local evidence that can inform health policy and humanitarian response.",2021,2022,University of Essex,388328.96,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Internally Displaced and Migrants,Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Uganda,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C14326,EP/V036394/1,GCRF_NF332 Ongoing impacts from the surge in sand mining during COVID-19: Enhanced river bank erosion hazard and risk in Vietnam's Mekong delta,"SE Asia's CV19 economic recovery plan is heavily reliant on an expanded construction industry, creating high demand for sand across the region. Sand is routinely mined from large rivers and is normally subject to regulation because, if it is removed more rapidly than it is replaced by river flows, it can trigger adverse socio-environmental impacts that hinder development. These include bank erosion - threatening homes and infrastructure - while over-deepened delta channels are also prone to saltwater intrusion. The Mekong delta is already experiencing these problems, but the issue highlighted here is that the CV19 'lockdown' - and potentially the recovery - has led to an upsurge in unregulated sand mining due to limitations in governance capacity. This proposal will spatially quantify this activity and predict the extent to which it will further stimulate bank erosion in the forthcoming monsoon season (when banks become saturated) and subsequent dry season (bank collapse is usually triggered during flow recession). Changes in exposed population as a result of internal migration pre- and post lockdown will also be estimated using expert knowledge verified with traffic volume changes, along with an assessment of exposed socio-economic assets (e.g., roads, schools), to establish changing spatial patterns of hazard, vulnerability and risk. This work is urgent because of concerns that CV19 related mining has primed the system for severe erosion during the impending flood season. The results will guide remediation efforts and aid efforts to promote stronger regulation of sand mining, both post CV19 and for any future disrupting events (including, but not limited to, pandemics) that could potentially stimulate an upsurge in illegal mining.",2021,2021,University of Southampton,422178.56,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Western Pacific,,,,United Kingdom,Viet Nam,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C14327,EP/V042947/1,GCRF_NF516 Increasing resilience in fishing communities to impacts of COVID-19 in northern Peru,"Peru is one the world's worst COVID affected countries. Gaps in social welfare, poor infrastucture and living conditions and high levels of informal employment exacerbate the impact of this disease. Artisanal fisheries are an important and overlooked activity which provides employment and basic nutrition for some of the poorest in rural areas. Thousands of jobs in the seadood supply chain are affected by the pandemic. In the Piura region, the impact on fishing communities is expected to be higher due to the large number of people involved in fisheries-dependent activities and the lack of alternative economic opportunities. There has been no systematic effort to document the impact of COVID on these communities. The Regional Government has identified a need for this information in order to respond with appropiate social welfare measures and is leading an Inter-Agency Consortium (IAC) to re-establish artisanal fisheries activities. This project will support the IAC by collecting and disseminating data on the impact of COVID in fishing communities. It will assess key fisheries, rigorously estimate the impact of the pandemic througout the supply chain and look at the way that this has, or needs to adapt to become more resilient. Throught the timely provision of relevant socio-economic information through a virtual online platform, this project will support decision-making by fishers, government and society in general, By engaging stakeholders in affected communities the project will develop recommendations for a sustained re-activation of fishing and associated activities.",2021,2022,University of St Andrews,261946.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Peru,Peru,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C14328,EP/V043064/1,GCRF_NF335 COVID19: Greening the Social and Economic Recovery in Ghana and Zambia,"This project will support a clean and resilient recovery from the Covid-19 pandemic in Ghana and Zambia. It will work with research partners, governments and other organisations in those countries to develop strategies that integrate economic recovery and climate change policies. Ghana and Zambia have been chosen because there is an opportunity to build on existing collaborations; there is a clear demand from policy makers for this research; and they have important differences that will enable lessons to be learned in other countries. The project has five main objectives. It will: 1. Understand the drivers, challenges and opportunities for a clean, resilient recovery in Ghana and Zambia 2. Investigate options for a clean, resilient recovery through the co-creation of participatory pathways for future development 3. Quantify the socio-economic, energy and climate implications of a clean, resilient recovery 4. Support government decision-making on recovery, climate action and development planning, including through information-sharing and the adaption of clean, resilient recovery initiatives from other contexts 5. Strengthen capacity, share knowledge and create equitable and enduring partnerships The project will focus in particular on the development and implementation of revised Nationally Determined Contributions (NDCs). Revised NDCs need to be submitted to the UN Framework Convention on Climate Change before COP26, which will be held in Glasgow in late 2021. This integration is critical not only for social and economic recovery in the short-term, but also for avoiding lock-in to carbon intensive development pathways that could undermine long-term resilience.",2021,2022,University College London,368240.64,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Ghana | Zambia,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C14329,EP/V043102/1,"GCRF_NF228 The COVID Observatories: Monitoring the interaction of pandemics, climate risks, & food systems among the most disadvantaged communities","Indigenous Peoples (IPs) are believed to be at particularly high risk from COVID, exacerbated by climate risks and socio-economic stresses. There is emerging evidence that national responses to the pandemic are compounding the vulnerability of IPs, exacerbated by little--if any--understanding on the unique pathways through which COVID will affect IPs. This project will address this knowledge and policy gap by documenting, monitoring, and examining how COVID is interacting with multiple stresses to affect the food systems of IPs globally, co-generating knowledge and capacity to strengthen resilience. Our focus on food reflects the fact that many of the risks posed by COVID stem from interactions with food systems, which for IPs are composed of a mix of traditional and modern elements. The work will be undertaken in collaboration with 24 distinct Indigenous peoples in 14 countries, and is structured around objectives which will: document the emergence of COVID and examine its impacts on food systems to-date; monitor and examine the real-time lived experiences, responses, and observations on COVIDs impact on food systems; compile and assess how COVID is being officially communicated and responded to; identify, examine, and promote interventions to strengthen resilience; and examine scalable insights for vulnerable populations across LMICs. Qualitative data collection is underpinned by a network of 'COVID Observers' within communities, in decision making roles, and researchers already located in the study regions, who will document their experiences and observations in reflective diaries over a 12 month period, capturing different stages of the pandemic and how multiple factors interact over time to create vulnerability and resilience. The global scope of the work builds upon ongoing and completed projects by team members in the study regions, leveraging considerable capacity and networks developed in work funded by DFID, UKRI, Wellcome Trust, FAO, and IDRC, among others.",2021,2022,University of Leeds,447852.8,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C14330,EP/V043110/1,GCRF_NF407 - Emergency strategies for mitigating the effects of COVID-19 in care homes in low and middle income countries,"In many developing countries there are large numbers of care homes for older people. Until the onset of the COVID-19 pandemic, they received little attention from policymakers or academics. There is now understandable concern that the pandemic will affect care home residents, as well as staff. Responsibility for care homes is mainly devolved to local governments, and many are looking to develop emergency plans. These need to take account of specific contexts, including scarce resources and very limited regulation of care homes prior to the pandemic. We will partner local government agencies in three countries (Brazil, South Africa and Mexico) to support the development and implementation of emergency plans, and to assess their effects on care homes. Based on consultations with a wider network of policy-makers and experts, we have developed a set of guiding principles (The CIAT Framework). We will work with local governments to put this framework into practice, refine it and assess its potential value for developing countries more generally. At the same time, we will develop an interactive online network with policy-makers and researchers interested in care homes and COVID-19, linked to an existing online policy network we have developed during the pandemic.",2021,2022,University of East Anglia,202429.44,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Americas,,,,United Kingdom,Brazil | South Africa | Mexico,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +C14331,EP/V043129/1,GCRF_NF437 High Performance Low Cost Ventilator (HPLV) project,"The unmet need addressed by the High Performance Low-cost Ventilator (HPLV) project is the shortage of ventilators for patient care in OECD DAC list countries. The global pandemic of COVID-19 has highlighted this lack of ventilators which is in-turn compounded by a shortage of trained staff available to operate them. Beyond COVID-19, there remain the critical requirements of caring for pneumonia patients and others suffering from acute respiratory conditions in the OECD DAC-list countries. This project takes as its starting point the HEV (High Energy physics Ventilator) developed by the CERN particle physics laboratory in Geneva with advice and guidance from WHO with the aim of being suitable for OECD DAC list use. HEV has been developed using techniques routinely used in the context of CERN research, including for delivery and regulation of gases, and for sophisticated monitoring and control. Nevertheless, HEV was designed to be reasonably priced, robust, easily maintained and able to operate in an environment where oxygen supply pressure is variable, power is unreliable and few trained staff are available. The result is a resilient and simple design with comprehensive in-built options for remote training, monitoring, and operation, which does not compromise on either performance or functionality, but allows easy operation via a multi-lingual user interface. Within this HPLV project, partners in Brazil will identify local difficulties encountered when ventilating patients and input that information to the design team working on re-engineering the HEV ventilator into an HPLV design. Regulatory experts in the UK will also provide valuable guidance on this re-engineering activity. As well as re-engineering an HPLV prototype in line with real-world advice from Brazil, the HPLV project team will provide the necessary documentation to accompany the HPLV design, such that it is ready for regulatory approval. This is a key milestone to enabling commercial organisations to bridge the gap between prototyping and manufacture for use in a medical environment. The end point of this project will be reached when the new re-engineered HPLV prototype has been successfully tested in Brazil and the technical file is available for companies to use when they license the design for manufacture and sale to OECD DAC list users.",2021,2022,Science and Technology Facilities Council,750993.92,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +C14332,EP/V043153/1,GCRF_NF345 Tackling Covid19 through co-production: engaging Brazilian vulnerable communities in facing the consequences of pandemics,"There is a long history of disconnection and lack of trust between vulnerable communities (slums and favelas) and public authorities in Brazil, due to diverse reasons, including failures in service delivery (e.g., sanitation, education, health), overuse of violence by the police force, and the presence of militias (parastatal power). Many social interventions for COVID-19 prevention and control require co-operation from citizens to be effective. Local communities and their local leaders know their daily needs, their areas, and the social environment better than the government. To cope with COVID- 19, and similar future crises, members of the vulnerable community need to be engaged as part of the solution, and given voice. Our proposal aims to enact co-production with members of these communities and municipal councils. Such councils are already established all over the country. The project will promote an exercise on co-production to design tactics and solutions to prepare neighborhoods for facing future interventions, and in particular vaccine delivery (SDGs goals 3, 10,11,16). Such co-production space would open up opportunities to share information, give voice to local leaders and community members. It is about increasing resilience, reducing social vulnerability, rebuilding trust, through co-production to cope with pandemic outbreaks. The process includes four stages: (i) identification of ""successful collective strategies"" in vulnerable areas of two Brazilian capital cities (Belem and São Paulo), looking at the determinants of such action, by interviews, (ii) extending the understanding through an extensive survey to others communities from the same cities, (iii) developing a mobile application to create a co-production milieu supporting people to jointly act with municipal councils, (iv) rolling out the initiative to others urban areas disseminating the results.",2021,2022,University of Essex,73235.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Brazil,Brazil,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C14333,EP/V04317X/1,"GCRF_NF362 Socio-economic, wellbeing and human rights related experiences of people with disabilities in Covid-19 times in South Africa","People with disabilities (PWD) are recognised globally as a large but often excluded and disadvantaged minority. The South African White Paper on the Rights of Persons with Disabilities (WPRD) (DSD 2016) estimates 12% of South Africans live with a disability. The South African (SA) government has ratified various international and regional disability treaties, but has no specific legislation for disability rights, these being dealt with in general antidiscrimination legislation. Thus, SA does not have the necessary frameworks to monitor, intervene, enable and provide justice for PWD (Sibanda 2015). This has become more apparent during the COVID-19 pandemic and lockdown in SA in March 2020. Much information has been gathered on how South Africans generally are experiencing the COVID-19 outbreak and the subsequent lockdown, but this does not gather the experiences and circumstances of PWD. Some COVID-19 studies relating to this population focus on specific impairments, on selected locations, or on particular challenges such as communication or mobility, but there is no countrywide data. A current international survey has recruited less than 50 PWDs in SA (Global Disability Rights Monitor 2020). Uniquely, we will do a national survey with people with all types of impairment, aiming to identify experiences and challenges PWD face during COVID-19. We will explore whether the SA National Disaster Management Act is seen to be compliant with the UN Convention on Rights of Persons with Disabilities (2017) and South Africa's WPRD. We will produce new comprehensive data revealing impacts of COVID-19 on PWDs and thus provide the Ministry of Women, Youth and PWD (MWYPD) with evidence to inform the development of a monitoring framework for the inclusion of PWD in mitigations during and after pandemics, shocks and crises. This study will investigate the experiences of people with diverse impairments (PWD) during COVID-19 and hear their perspectives on what could be improved, revealing whether they feel their human rights have been upheld or denied during this time of uncertainty. These findings will then be used to mobilise/influence the SA government to address any rights-based concerns and exclusionary oversights across sectors. It will provide evidence and recommendations to inform the development of a framework (already recognised and documented as needed by MWYPD) to ensure the realisation of the rights of people with disabilities during future national disasters, shocks and crises such as pandemics and similar. After initially reviewing relevant literature, we will refine our survey tool and conduct the first national disability survey asking PWD for their views, with a sample size of approximately 4000 PWDs in South Africa. Mobile phone and online platforms (ICT) will be used to administer remotely, an electronic quantitative and qualitative survey, adhering to COVID-19 lockdown regulations. IDS and HSRC will work in partnership with member organisations, affiliates and partners of the National Council of and for Persons with Disabilities (NCPD) to design the survey and recruit participants. We will ensure that a wide cross-section of this subpopulation is reached (balancing disability type, race, class, gender, age), respondents being adults with disabilities (or parents and caregivers) who volunteer to participate. Personal information will be protected as per the Protection of Personal Information Act (2013). The 9-month study is unique in focussing specifically on the perceptions of South African PWDs and their concerns during COVID-19 and related events and then lobbying for their recommendations to inform a new framework to guide improved disability inclusive practices generally and in future crises. Findings will be shared nationally, regionally and globally to a range of formats (verbal and written), for various including disability interested audiences, activists, academics, service planners and policymakers",2021,2021,Institute of Development Studies,141678.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2020 +C14334,EP/V04320X/1,GCRF_NF225 - Improving community engagement with COVID-19 public health messages in hard to reach communities,"Pakistan has one of the highest number of confirmed coronavirus cases in the world, with potentially devastating health and economic implications for a population heavily dependent on daily incomes. It is important to ensure that communities understand and act on public health messages to limit the spread of further coronavirus outbreaks. This may be difficult to achieve in hard to reach populations, particularly when such messages are not sensitive to their culture. Previous health crises have highlighted that mistrust and rumour can under-mine public confidence in the scientific evidence and can be a dangerous hindrance to response efforts. Our study will explore the cultural barriers and facilitators to communicating public health and safety guidance in rural communities in North West Pakistan. We will focus on an impoverished brick-kiln community near Peshawar, where households have average income of less than one US dollar a day, many have limited access to clean water and unequal access to education and healthcare. We will work with the community to develop a response that is both effective and consistent with local interests. As well as finding out about best ways to engage the community to follow public health advice, the community will decide on the material resources needed to support and implement these guidelines, such as providing a clean water supply. Researchers will work with community members to produce a toolkit that will help to support communication, community engagement and risk minimisation in similar hard to reach communities for future health crises.",2021,2022,University of Central Lancashire,195532.8,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Eastern Mediterranean,Eastern Mediterranean,,,,Pakistan,Pakistan,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2020 +C14335,EP/V043218/1,GCRF_NF292: Social and environmental impacts of the Covid-19 pandemic in Vietnamese provinces bordering China and Laos following border closure,"Northern provinces in Vietnam that border China and Laos have been severely affected economically by the current Covid-19 pandemic. These provinces have high populations of ethnic minority groups such as the Tay, Nung, Hmong and Thai who rely in part on cross border migration to sustain their families' livelihoods. However, the Covid-19 crisis has led to the closure of international borders and migrant workers have been forced to return home. With this, major sources of income were foregone and because loss of employment in a foreign country is not recognized by Vietnamese social protection mechanisms in the context of this crisis, entire communities have had to develop their own coping mechanisms. For example, some communities have increasingly started to rely on their surrounding natural environment, including freshwater resources and forest products (both timber and non-timber products). It is not clear how effective these and other coping measures are, nor what the long term consequences on natural resources will be. As there are many uncertainties regarding the evolution of the pandemic and the potential reopening of borders, we aim to investigate how the current crisis has shaped the relationship between vulnerable communities and their natural environment by combining different scientific approaches. Our research will achieve impact locally, by providing scientific evidence to local and national policy-makers as to the situation of vulnerable communities and of their environment, as well as developing future scenarios of this situation under various assumptions of the evolution of the pandemic and potential cross border movement. We are partnering with local authorities and aim to provide scientifically-grounded advice on amending existing policies so that ethnic minority-dominated regions can receive the appropriate support to ensure we are ""leaving no-one behind"", the stated aim of the United Nations Sustainable Development Goals.",2021,2022,University of Glasgow,236006.4,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,South-East Asia | Western Pacific,,,,United Kingdom,Viet Nam | Lao People's Democratic Republic,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C14336,EP/V043226/1,GCRF_NF359: Modelling the exposure risk tradeoff between public transit and private paratransit for transport decision making in the era of Covid19,"A safe and functioning transport system is vital to maintain economic activities in countries, developing or not. In most developing countries, the transport system is characterised by a crowded bus transit and micro-transit systems, supplemented by paratransits such as motorcycle taxis and autorickshaws. The paratransit sector is also a large source of employment (e.g. 3 Million motorcycle taxis in Nigeria, 300,000 in Kampala, Uganda, 104,000 in Dhaka, Bangladesh). The COVID19 pandemic has massively disrupted the transport sector and economic activities. In the project countries, motorcycle-based paratransits are banned from operating in order to maintain safe distances. In addition to disrupting travel and affecting the primarily poor users (prices in other modes have gone up), this has also resulted in massive unemployment and poverty among the drivers. However, there are also serious concerns about the safety of passengers in crowded buses or micro-transit vehicles, where maintaining appropriate distances are nearly impossible, and paratransits can be a viable alternative. The risks of virus exposure is also high in high occupancy vehicles due to the closed nature of the vehicles compared to the open nature of motorcycles and semi-open nature of autorickshaws. It may also be possible to mitigate risks in paratransits through barriers or shields. However, there are no studies investigating the relative risks of these modes, with or without the mitigation measures. The project aims to model the exposure risk in different types of transport modes in order to allow policymakers to make an evidence-based optimum decision. The physics-based computer modelling will be accompanied by user surveys to understand their travel pattern, preferences and acceptance of various mitigation measures (such as shields designed using the models). Given the prevalence of micro-and paratransits in many other DAC countries, the results will be useful for other similar DAC countries too.",2021,2021,University of Leeds,215010.56,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2020 +C14337,EP/V043250/1,GCRF_NF452 Climate Change & COVID-19 (CCC19): Achieving a Sustainable and Equitable Recovery in Malawi and Rwanda,"Most of our responses to the COVID-19 pandemic are focused on the immediate needs of affected countries and populations and their swift economic recovery. In developing countries, where the effects of climate change are now made even worse by COVID-19, there is a lot of appetite for making this recovery sustainable and equitable. Specifically, we need to understand how COVID-19 has affected local people's ability to withstand droughts, floods and sea-level rise and the prospects for adapting to and mitigating climate change in these countries. However, the data and knowledge on how to achieve this are lacking. This project will invite local community members as well as practitioners from government, development, private sector and community-based organizations in Rwanda and Malawi - two countries simultaneously affected by the pandemic and climate change - to participate in interviews, focus groups and surveys on this topic. Participants from local communities will also be asked to produce video stories of their experiences of COVID-19 and climate change in order to put a human face on both crises and ensure local voices are heard at the highest levels of government in both countries. The findings of this research will inform the work of the Malawian and Rwandan ministries responsible for health, climate change and environment (key project partners). This will be achieved through a range of products and events, including reports, journal articles, a documentary, an interactive website and case-study leaflets. We will hold two simultaneous end-of-project workshops with online participation from the UK, during which all stakeholders will be able to discuss and exchange their experiences and inform policy development. The project's ultimate aim is to ensure that the way these countries plan and carry out their recovery after COVID-19 is environmentally sustainable and socially equitable, so that it does not harm the climate or the most vulnerable people.",2021,2021,Glasgow Caledonian University,212295.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,Malawi | Rwanda,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +C14338,EP/V043315/1,GCRF_NF391 Maximising benefit and minimising the harm of COVID-19 control measures on child and women's health in four Sub-Saharan African countries,"COVID-19 is challenging everywhere because many of the measures to control the disease also produce negative effects. This is especially the case in Sub-Saharan Africa (SSA) where health systems are relatively under-resourced, where poverty rates are high, and where countries have to simultaneously deal with other health challenges such as those presented by HIV/AIDS, TB, diarrhoeal disease, malaria and malnutrition. Previous research conducted by ourselves has shown strong anecdotal evidence of health systems disruption and other unintended harms. Concerns include the effects of school closures, reduced household food income, worsening food security, reduced vaccination coverage rates and the effects of certain COVID-19 control measures having a worse impact on the health of girls and women. We also found countries adopting different approaches and actions to control COVID-19. Building upon these findings, we intend to: 1) describe and evaluate the impact of COVID-19 and COVID-19 control measures on health systems functioning, child health and women's health in Ghana, Tanzania, Uganda and Zimbabwe; 2) identify how COVID-19 control measures can be improved; and 3) enable the sharing of lessons and information across countries. The main deliverables will be: - a set of country case study reports incorporating new knowledge about how COVID-19 control measures impact on the health of children and girls/women, with recommendations for how children and women may be better protected; - a report describing the different approaches and strategies taken to control COVID-19 across the four countries, with recommendations on how research and evidence can be produced and harnessed to strengthen future policy making and implementation These reports will form the basis for shorter policy briefs, lay summaries and peer-reviewed publications. The project will also deliver: - a series of in-country stakeholder discussions and meetings and establish opportunities for cross-country dialogue; - a collaborative research network that will set the foundations for future research studies. The activities and outputs proposed here will complement the efforts of government agencies and non-governmental organisations (including UNICEF, Save the Children and UNFPA) working to promote and protect child and women's health. And it will identify critical knowledge gaps and priorities for further research, including in-depth epidemiological studies, intervention studies and in-depth social science inquiries.",2021,2021,Queen Mary University of London,589373.44,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,Gender,,,United Kingdom,Ghana | Tanzania | Uganda | Zimbabwe,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Social impacts | Health service delivery,2020 +C14339,EP/V04348X/1,"GCRF_NF278 Building evidence on households, firms and value chains to support economic policy decisions under COVID-19","IGC has worked with policymakers in the nine named countries to identify key research questions to understand how COVID-19 is impacting their economy, how the economic recovery can be accelerated, which policy interventions should be implemented and how assistance should be provided to those most in need. Our Co-Investigators, based in the named DAC-list countries, are uniquely positioned to implement a co-generation approach with policymaker partners to design research projects that will inform key policy decisions in the next 18 months and so will maximise impact from the research. Our Principal Investigator, IGC's Research Director, will leverage IGC's network of world class researchers to work with Co-Investigators to design high quality and robust research. This proposal will enable us to fund around 30 individual studies, all addressing first order priorities for policymaker partners, and building on the 34 COVID studies we have already launched. Research will combine existing administrative data, which Co-Investigators have good access to and familiarity with, and new data through phone surveys. Data priorities include monitoring value chains, firms and households' economic activity, and measuring the effectiveness of policy interventions on economic agents. We will feed data and research findings back to our existing policymaker contacts, including monitoring dashboards, infographics and appropriate policy options, to facilitate real-time, evidence-based decision making in the participating countries. The two main research activities to be carried out under this project are: - Monitoring and tracking economic activity, focusing on the post-lockdown economic recovery, through descriptive analysis of administrative data and of new survey data generated using carefully designed survey instruments implemented by phone. The analysis carried out will help identify which firms and households are most affected by the economic crisis, the main constraints they are facing and the support they need from governments. Results will be made directly available to policymakers through a series of dashboards and high frequency policy reports. - Testing the effectiveness of policy interventions by building on sample frames from previous randomized control trials to measure the impact of current interventions and, where appropriate and feasible, of new interventions co-generated with policy makers. Comparative analysis undertaken by local and UK-based researchers will use crosscountry and cross-sector variation in policy interventions to assess the effectiveness of these interventions.",2021,2022,London School of Economics and Political Science,746819.84,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Economic impacts | Systemic/environmental components of capacity strengthening,2020 +C14340,EP/V044613/1,GCRF_NF252 Co-surveillance of Wasterwater and Environmental Water Samples for SARS-CoV-2 and Pathogenic Viruses in South Africa and Nigeria: Incidence,"Information about SARS-CoV-2 levels circulating in the community is an essential part of developing an effective strategy to prevent the further spread of COVID-19 globally. Testing of individuals is time consuming, costly and currently does not capture a large proportion of the population. Wastewater monitoring of SARS-CoV-2, shed in faeces from infected individuals, including asymptomatic cases, provides an alternative approach. It has distinct benefits, obviating community sampling bias, and providing a cheap, non-invasive process to determine the level of infection in a large community within a single sample. However, this method cannot be directly implemented in many developing regions where wastewater is released into the environment without any treatment. Such pollution raises concerns about the environment-based transmission of the disease, which has not been studied. Our project aims to assess the prevalence of COVID-19 in two sub-Saharan countries, South Africa and Nigeria, using wastewater-based epidemiology and environmental surveillance. We will measure SARS-CoV-2 RNA concentrations to investigate the spread of COVID-19 at a community level. We will also assess the occurrence of other, common and emerging virus strains (e.g. enteroviruses, measles and influenza) to evaluate the effect of lockdown measures on the transmission of viral diseases. We will also determine the health risks associated with polluted environments using infectivity assays and determine the most common SARS-CoV-2 variants circulating in each country using environmental metaviromics. Working alongside public health stakeholders, our findings will allow enhanced decision making on the containment of COVID-19 and achieving UN Sustainable Development Goals 3, 6 and 11.",2021,2022,Bangor University,252029.44,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa,,,,United Kingdom,South Africa | Nigeria,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen | Disease transmission dynamics | Disease surveillance & mapping",2020 +C14341,EP/V048414/1,GCRF_NF411 Effective point-of-use STERilisation of medical equipment using Ethylene Oxide (STEREO),"The project addresses the needs of effective chemical sterilisation that is essential to manage virus spread and in everyday healthcare. Currently, the most effective sterilisation can be performed with ethylene oxide, a chemical that is not available in Botswana or South Africa, or many other African countries. We propose a new process for producing ethylene oxide for the most effective sterilisation, aiming for equal access to high-level healthcare in DAC-list countries. The process will use inexpensive and widely available ethanol as a starting substrate. Our research goal is to demonstrate ethylene oxide production at the rates and in quantity needed for 1 m3 of stand-alone sterilisation units.",2021,2022,University of Cambridge,312614.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C14342,EP/W010917/1,Low cost air quality device for virus removal from indoor air environment and public transport (EP/V049100/1),"SARS-CoV-2, the virus that causes the disease Covid-19, is primarily transmitted through respiratory droplets which linger in enclosed spaces, often exacerbated by HVAC systems. Although research to improve HVAC handling of SARS-CoV-2 is progressing, currently installed HVAC systems cause problems because they recirculate air and also use ineffective virus filters. This project will develop a novel method of eliminating SARS-CoV-2 and future viruses in enclosed spaces using Photocatalytic Oxidation (PCO) technology, previously employed to remove organic contaminants and compounds from air streams using the irradiation of titanium dioxide (TiO2) surfaces with ultraviolet (UV) lights causing the disintegration of organic compounds by reactions with oxygen (O) and hydroxyl radicals (OH). The O and OH reactions can also destroy viruses. Using the established results from previous R&D, the project will develop a novel TiO2 coated copper fibre mop system, which will both act as a fan and provide the essential very large surface area for UV irradiation. Research will include optimizing UV frequencies, intensity, and improvement on photocatalytic oxidation by doping of TiO2 with metals, followed by in vitro studies investigating the effects on SARS-CoV-2, and other endemic coronaviruses. The rotating fibre fan, illuminated by a high intensity UV, allows viruses to be eliminated in an efficient, nearly silent system, adaptable for small or larger applications. Engineering will include optimization of two demonstrators: a low-profile wall unit and free- standing floor unit. These low cost, efficient systems will be demonstrated to industry to allow rapid adoption for buildings and public transport systems.",2021,2022,University of Nottingham,335333.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C14343,EP/W01114X/1,"Development and manufacturing of innovative, low-cost, mass-produced, environmentally friendly filters and masks protecting against COVID-19","Given the surge in demand for masks to protect against CONVID-19, there is huge investment for new mask manufacturing plants in UK. A shortage of specialised mask materials points to the need to also manufacture these materials in UK. Enlisted in this herculean effort, we have assembled a team of industrial partners, including mask manufacturers, an equipment manufacturer, and testing companies. Our project aims at bringing manufacturing of filters and masks to the UK, lowering the cost and developing a roll-to-roll process of additive manufacturing using low-cost, abundant and environmentally-friendly materials. The principal idea of this project is to select, after testing, a range of natural-fibre cloths, to be used as substrate for additive manufacturing. Such substrates will be coated with a novel porous layer with functional groups trapping the COVID-19 and other high-risk viruses. Electrospinning is proposed as our additive manufacturing technique, where the assembly of coating layer(s) and cloth substrate will protect against the virus by filtering it, depending on porosity, pore size, fibre orientation, coating layer thickness and functional groups of coating and cloth. The proposed project includes the following tasks: (a) molecular simulations to screen materials and functional groups in terms of their binding energy with the virus spike; (b) continuum infiltration mechanics simulations to investigate the virus migration through the porous material assembly, as well as the air flow for breathing in the case of masks or air flow filters; (c) development of the electrospinning to a continuous roll-to-roll process; (d) material and product testing.",2021,2022,University of Surrey,660604.16,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C14344,EP/W011212/1,XAIvsDisinfo: eXplainable AI Methods for Categorisation and Analysis of COVID-19 Vaccine Disinformation and Online Debates,"UK vaccination rates are in decline and experts believe that vaccine disinformation, widely spread in social media, may be one of the reasons. Recent surveys have established that vaccine disinformation is impacting negatively citizen trust in COVID-19 vaccination specifically. As a response, the UK Government agreed with Twitter, Facebook, and YouTube measures to limit the spread of disinformation. However, simply removing disinformation from platforms is not enough, as the government also needs to monitor and respond to the concerns of vaccine hesitant citizens. Moreover, manual detection and tracking of disinformation, as currently practiced by many journalists, is infeasible, given the scale of social media. XAIvsDinfo aims to address these gaps through novel research on explainable AI-based models for large-scale analysis of vaccine disinformation. Specifically, vaccine disinformation will be classified automatically into the six narrative types defined by First Draft. A second model will categorise vaccine statements as pro-vaccine, anti-vaccine, vaccine-hesitant, or other. We will investigate explainable machine learning approaches that are human interpretable: both in detecting errors and weaknesses of the models and in providing human-readable explanations of the models' decisions. XAIvsDisinfo will also create two new multi-platform datasets and organise a new community research challenge on cross-platform analysis of vaccine disinformation, as follow-up from our RumourEval one. Our XAI models and tools will be integrated into the open-source InVID-WeVerify plugin, for take up by journalists and fact-checkers. The project outputs will also contribute to evidence-based policy activities by the UK government on improving citizen perception of COVID-19 vaccines.",2021,2022,University of Sheffield,295257.6,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2021 +C14345,EP/W011840/1,COVID-19: Bayesian inference for high resolution stochastic modelling for the UK,"We will develop an efficient and robust MCMC-based framework for fully Bayesian inference methodology for spatially explicit, stochastic, and partially observed meta-population epidemic models within human populations. This will be applied to the current UK Covid-19 epidemic. We particularly focus on the challenge of providing continuously updated parameter estimation and risk assessment in the face of censored data observations and hence detailed age- and space-specific predictions of Covid-19 prevalence and incidence in the UK. Our predictions will be targeted at disease management, providing early warning of spatial ""hotspots"" of epidemic resurgence as Behavioural and Social Intervention (lockdown) measures are lifted, as well as informing targeted disease surveillance to space- and age-related sub-populations. We respond to the observation that existing differential equation based models informing SAGE cannot operate at high population resolution, since as meta-populations get smaller, stochastic fluctuations intrinsic to the epidemic process begin to dominate case observation noise. Whilst stochastic models of Covid-19 spread (based on pre-existing influenza models) do exist, methods to fit them at scale in the face of changing data availability require development. To address this, we will extend our existing Bayesian approach to real-time risk prediction for individual level models, developing a data-augmentation MCMC approach to state-transition models defined on high-dimensional meta-population structures. Inference and forward simulation algorithms will be built using Google's TensorFlow library, providing appropriate balance between rapid algorithm development and fast GPU-accelerated computations to ensure that our results are timely, and appropriate for Covid-19 decision support across the UK.",2021,2022,Lancaster University,193794.56,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2021 +C14346,EP/W011956/1,"Waves, Lock-Downs, and Vaccines - Decision Support and Model with Superb Geographical and Sociological Resolution","This proposal aims at further developing, validating, and deploying the JUNE model for the simulation of the spread of COVID-19 in the United Kingdom and the impact of medical and non-medical mitigation strategies. Recently constructed, JUNE combines superb geographical and sociological resolution in its virtual population model with a detailed, flexible and adjustable simulation of daily activities and the ability to include mitigation strategies and other interventions, to asses their effect. JUNE is already being used by NHS England to gain insights into the nature of the disease and the dynamics of its spreading, thereby informing operational planning and supporting decisions. In this proposal we will 1. continue to provide valuable insights for the NHS, PHE, and the UK government, for example the impact of further complete or partial lock-downs, of the tier system and possible extensions and modifications, and of different vaccination protocols. This includes, in particular, the application of cutting-edge Bayesian methods for uncertainty quantification in projections of possible futures, and the development of robust data assimilation protocols to improve short-term predictions. 2. further refine the population model, with special emphasis on the transmission dynamics and conditions in minorities and on the effect of socio-economic factors on infection and fatality rates. We will also include models for multiple infectious diseases affecting the population concurrently, to quantify the impact of seasonal flu the resulting demands on the health care system. As a by-product we will fully document the code and produce a convenient user-interface, to facilitate its use in future epidemics, thereby turning it into an enduring national asset.",2021,2022,Durham University,453579.52,Other,Not applicable,Not Applicable,Unspecified,Minority communities unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2021 +C14347,EP/W01226X/1,A Visual Analytics and Multi-Objective Optimisation Approach for Balancing Economic and Public Health Objectives through Compartmental Models,"Modelling of disease spread continues to play a crucial role in the response to the COVID-19 pandemic. There is light at the end of the tunnel with effective vaccines, but it will take until the summer of 2021 for distribution to be widespread, and re-vaccination may be an ongoing requirement. In the meantime, hybrid solutions are required to manage non-pharmaceutical interventions (NPI), that minimise the restrictions to our daily lives while suppressing transmission and maintaining the integrity of our healthcare systems. Realistic models are publicly available to predict the spread of the virus. Varying the parameters of these models can be used to represent tentative policy actions, and the consequences are deduced in simulations of the model. Typically, the main objective for identifying effective policy actions has been to reduce the infection rate. However, often there are multiple, potentially conflicting, objectives that require optimisation in parallel. For instance, we may want policies that reduce the hospital occupancy, while simultaneously reducing economic impacts. Our goal is to provide a generic visual analytics framework to explore the parameter space of complex models as well as the trade-offs between objectives to inform policy makers. Specifically: 1. A scalable visual analytics framework for parameter space exploration of feasible regions of the parameter space for complex compartmental models in order to identify effective policy actions. 2. Extend this framework to handle multiple objectives: reduction of transmission to high risk groups, overall cases and deaths, hospital costs, thresholds for circuit breakers, and economic factors.",2021,2022,Swansea University,236808.96,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Approaches to public health interventions | Policy research and interventions | Economic impacts,2021 +C14348,EP/W012294/1,A Multimodal COVID-19 Database for Research,"The proposed project addresses one of the key UKRI priority areas of preparing data sets to defined quality standards by delivering a Multimodal Database for COVID-19 Research, a comprehensive and easy-to-use database for creating and validating epidemiological models. Modelling, machine learning, digital and data approaches to understanding the COVID-19 pandemic will shape policy decisions over the coming year. Such research requires rich and standardised data at a fine geographical level and of multiple modalities: epidemiological, mobility, socioeconomic and more. Large quantities of COVID-19 data are collected both in the UK and around the world. However, sourcing and linking data of different modalities are major burdens for researchers, owing to the lack of standardisation. There is a clear need to establish a central repository to facilitate world-class research immediately and in coming years. Building on our extensive voluntary work on the OxCOVID19 Database (https://covid19.eng.ox.ac.uk/), we seek funding to expand our global coverage, deepen our focus on the UK, design new interfaces for diverse users, develop stronger infrastructure for increasing demand, and grow our user numbers. This database will enable data linkage for research, delivering consolidated, well-formatted data in a way that avoids duplication of effort by multiple research groups and accelerates research by removing barriers to entry.",2021,2022,University of Oxford,311290.88,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2021 +C14349,EP/W01257X/1,Rethinking Public Technology in a COVID-19 Era,"What do public interactive information displays, vending machines and pedestrian crossings have in common? They are just a few of the ubiquitous yet essential public infrastructures that rely on buttons or touchscreens; common interactions that, until recently, were considered perfectly safe to perform. The Covid-19 pandemic, however, has created unprecedented opportunities for technologies that minimise interaction with shared devices. While recent advances in sensor technology and artificial intelligence have enabled consumer products that can respond to other modalities such as speech, gestures and faces, the underlying interaction paradigms have not been widely studied in public-facing settings (as opposed to specialised contexts such as operating theatres or with personal technologies in public). As a result, we do not know how usable, accessible, inclusive or effective these potential solutions are. The project will begin by surveying the landscape of touch interactions in public services to learn through observation how they are being adapted or avoided. Drawing on these insights, we will develop and integrate a suite of touchless technologies into exemplar public-facing services in a test-bed city, facilitated by our partner, Swansea Council. These flexible longitudinal deployments will allow us to study usage in-situ to determine the most appropriate, robust and cost-effective ways of facilitating safe, touchless interfaces for the Covid-19 era (and any subsequent outbreaks). The result of this work will be a public-facing touchless interaction design methodology and open-source toolkit of blueprints and techniques that can be integrated into existing infrastructures and used to inform the design of future installations.",2021,2022,Swansea University,293288.96,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C14350,EP/W01484X/1,Application of multiscale algebra and topology to understanding heterogeneity in the immune response to SARS CoV 2 infection,"The basis of variability between patients in their immune response and outcome from acute SARS-Cov-2 infection remains poorly defined, limiting opportunities for targetted intervention. The generation of multi-modal molecular and immunological data sets profiling the immune response across individuals and over time provides opportunities to address this but maximising the informativeness of such datasets remains a major roadblock. Here, we propose to address this through application of state-of-the-art integrative mathematical and computational techniques to analyse data together and extract novel insights. We will use algebraic systems biology approaches to combine algebraic geometry, data tensors, topological data analysis and network theory to encode multidimensional and multi-indexed data in order to identify signatures and cellular drivers of heterogeneity in the host immune response leading to different disease severity. We will apply this to data recently generated by the Oxford COVID-19 Multi-Omic Blood ATlas (COMBAT) consortium which includes high resolution clinical phenotyping, single cell profiling of the cellular blood compartment for composition, repertoire, transcriptomics and epigenomics, the plasma secretome, serology, viral sequencing, metagenomics and host genotyping. Our application is timely and urgent given availability of data and opportunity for impact. The work will promote collaboration between medical and mathematical sciences, promoting cross-disciplinarity. The analysis will provide novel insights into pathophysiology, identify key networks and nodal points for targetted intervention that will enable development of immunmodulatory therapy, and define biomarkers informative for the individual immune response that can be taken forward for validation and enable development of a precision medicine approach to COVID-19.",2021,2022,University of Oxford,233583.36,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +C14351,EP/W015153/1,WELD: Integrated Cyber-Infrastructure for Scalable Data-Driven Research into COVID-19,"The project will implement a unifying cyberinfrastructure based on automated machine-actionable policies that will enable data-driven clinical and medical research across the four nations and produce evidence essential for making rapid decisions on the UK's response to the COVID-19 outbreak. The research explores the development of integrated computing, modelling, simulation, and information technologies as the basis of cross-disciplinary research for collaborating teams investigating COVID-19 and SARS-CoV-2. The application will implement a ""cloud native"" software infrastructure for federating distributed healthcare data across the Trusted Research Environments and include methods for working with ensemble collections of data. The result will quantifiably improve existing model- and statistically- based methodologies for evaluating vaccine efficacy and risk prediction using live NHS data in clinical research environments. A unique contribution will be ""policy-based"" data federation techniques that allow each devolved nation or Trusted Research Environment to control its use of a shared UK-wide data collection, across regulatory boundaries, while guarding against data exfiltration. This capability, which has never been addressed, is fundamental to providing a secure evidence base for effective data analysis and scientific discovery of COVID-19 at UK-wide levels. The methodology draws on state-of-the-art in data abstractions and virtualisation levels, provides greater flexibility for automation and re-use across the lifecycle, and addresses the need for a more systematic, community-based approach to data and metadata as part of a shared solution. The architectural model will instruct HDR-UK strategic decision-making responding to COVID-19 and future pandemics that require an improved technology readiness level.",2021,2022,University of Oxford,1537500.16,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems | Health leadership and governance,2021 +C14352,EP/W015609/1,Reducing the Infectivity of SarsCov2 on PPE gowns used in heaLthcare Environments (RIPPLE),"Reducing the Infectivity of SarsCov2 on PPE gowns used in heaLthcare Environments (RIPPLE) The COVID-19 pandemic has had significant and far-reaching effects for everyone. While we now have effective vaccines, some people are still vulnerable to the coronavirus and especially to its variants. In particular, people who have immune systems that do not function well, or the very elderly and very young in hospitals and health or social care settings are still at risk. One of the major ways we can reduce the risk of infection is by wearing personal protective equipment, such as gowns and masks. However, when healthcare staff are looking after a COVID-19 patient, these items become contaminated with virus. Taking them off can result in viruses being shaken off and contaminating the environment or being breathed in by other people. This could lead to further infections. Our idea is to make PPE gowns specifically sticky to the COVID-19 virus (SARS-CoV-2). By doing this, the virus will be held on the gowns for disposal in clinical waste bins, rather than being released into the healthcare environment or breathed in. By reducing the amount of virus available to infect people, we hope this will reduce the risk of COVID-19 for those who are particularly vulnerable to infection. To do this, we are working with industrial partners to create small molecules (ligands) that are designed to stick to a part of the virus surface (spike glycoprotein). We will create lots of ligands and use a safe virus with the same spike glycoprotein (lentivirus vector) to find out which ones stick the best. When we have chosen the best ligands to work with, we will see which ones can be attached to the materials used in PPE gowns. We will then make sure these still stick to the lentivirus vector by looking at how long and how strongly they bind. Finally, we will use the specialised facilities at the University of Leeds to see how the new sticky materials perform with live SARS-CoV-2 virus to make sure they will work well in the real world. Our industrial partners, Astrea and NIRI have a lot of experience with making ligands and specialised materials on large scales, so that the ligand-material combination that successfully binds SARS- CoV2 can be produced in large quantities and reach staff in the health and social care sectors as soon as possible.",2021,2022,University of Leeds,346350.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C14353,ES/W001861/1,Assessing the Court System's Response to the COVID-19 Pandemic in Eviction Cases,"The COVID-19 pandemic has had a profound effect on household debt evidenced in part by a significant increase in rent and mortgage arrears (Brady, 2020 and Wilson et al, 2021). In response, the landscape of eviction in England and Wales has changed fundamentally. Lenders, landlords, regulators and the court system have all introduced changes designed to mitigate the impact of the pandemic on households in an effort to assist them in keeping their homes, for now (see Wilson et al, 2021). With all legal claims for eviction halted until 20 September 2020, the resumption of legal proceedings has taken place under a new system known as the 'Overall Arrangements' which will operate from 20 September 2020 until 30 July 2021. In addition, a new 'Housing Possession Mediation Pilot Scheme', intended to run for six months, began on 1 February 2021. These initiatives are designed to increase opportunities for the parties to reach agreement and avoid the need for a substantive court hearing, thereby reducing the number of evictions and relieving pressure on the already overburdened court system. Given the temporary nature of these schemes, it is imperative that an assessment of their effectiveness is undertaken before the end of July 2021. This project will achieve that aim by collecting data from, among others, occupiers threatened with eviction and legal practitioners on the frontline of eviction cases. An analysis of that data will offer a unique insight into the impact of the COVID-19 pandemic on household debt and home loss, how occupiers respond to and engage in the arrears process and the effectiveness of the new initiatives on handling possession cases. The findings of this project will contribute new knowledge to a range of academic disciplines including law, business, economics, and psychology. By working closely with key stakeholders, including housing providers, legal practitioners and the Ministry of Justice, it will also give rise to knowledge exchange and impact. It will, in particular, inform urgent policy decisions regarding both the current and future development of the eviction process and thereby assist some households in their attempts to avoid losing their home.",2021,-99,University of Hull,56215.04,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C14354,ES/W002124/1,Learning inequalities during the Covid-19 pandemic: a longitudinal analysis using the UK Understanding Society 2020 and 2021 data,"The spring of 2020 saw a widespread and prolonged closure of schools across the UK due to the Covid-19 pandemic. Schools began a phased reopening in July 2021 and in January 2021 closed for the second time. The resulting transition to distance schooling has impaired students' learning and transferred to families a great deal of responsibility for educational activities, thus exacerbating inequalities in learning opportunities by socio-economic status. The current debate on the extent of the learning loss, the possibility of new school closures, the activities that are necessary to remediate the learning loss, and the nature of the 2021 school assessment would benefit from a timely analysis of the learning opportunities that children had during the two school closures. Our project will provide such an analysis. It will use longitudinal data from the April 2020 and January 2021 Understanding Society (USoc) Covid-19 surveys to offer the most recent insights into learning opportunities in the United Kingdom during the January-March 2021 school closure. As both surveys interviewed the same families, are representative of the UK and can be linked to previous US surveys, we are able to construct a rich, reliable and longitudinal dataset of around 1300 children in primary school and 1500 children in secondary school. Dr. Birgitta Rabe and Professor Stephen Machin are currently leading two separate ESRC projects on the effects of the Covid-19 pandemic on educational learning opportunities, attainments at national exams and higher education participation (respectively projects ES/V015222/1 and ES/V010433/1). While their cross-sectional research design focuses on specific points in time, our project is the first to use panel data covering both school closures to offer a longitudinal analysis of learning opportunities. The newer USoc survey was prompted by the new school closure, which was announced in January 2021, hence the application through the ESRC Time Critical Covid-19 Call. We will analyse whether the uptake of schoolwork - which reflects both the school provision and how families engage with it - changed between the first and the second school closure and whether the gap between advantaged and disadvantaged families in schoolwork has narrowed or widened. We define advantage using a wide range of characteristics including: parental occupational category; availability of computers at home; working patterns such as working from home and being in furlough; and family structure. In our previous study we suggested that in case of school closure inequalities in learning can be remediated by providing students with better access to IT and by providing online academic tutors to compensate for the absence of parents who cannot work from home. Thanks to our existing relationship within academics, a clear dissemination plan which will be delivered with the cooperation of Public Policy at Southampton, we expect to match the impact of our previous research on learning inequalities during the first school closure, which included being featured in more than 100 national and regional outlets such as the Guardian, impact sessions with MPs Michael Tomlinson and Alan Whitehead and impact event contributions for the Scottish Government. Our research will enable policy makers and practitioners to evaluate whether distance learning has improved during the second transition to home-schooling, and what new policies are necessary to mitigate the consequences of the school closures and prepare for possible future school closures.",2021,-99,University of Southampton,40989.44,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C14355,ES/W002868/1,Approaching the cliff edge? The intentions of private sector landlords on cessation of the eviction ban in Scotland,"The Private Rented Sector has grown considerably over the last 25 years and is now a crucial part of the UK's housing mix. The sector provides easily accessible accommodation for young, mobile, transient populations, but is increasingly being used to provide long term accommodation for vulnerable groups who in earlier times might have been able to access local authority or housing association accommodation. With the arrival of Covid, The Scottish Government made a series of temporary changes to the legislation that governs the tenant eviction process. These changes have been made over concerns that Covid-19 would result in an increase in evictions resulting in tenants being made homeless and support services being overwhelmed. The changes include extensions to notice periods (up to 6 months) for certain grounds, the introduction of 'Pre-action requirements', and the re-classification of all grounds as discretionary. Importantly the changes also include a ban on evictions due to tenant non-payment, until the end of September 2021. The amendments apply to all areas under a Tier 3 or Tier 4 lockdown. Whilst these changes are believed to have safeguarded tenants and support services in the short term, they have not addressed the underlying problems, and unprecedented levels of rent arrears have accumulated for private landlords. Every additional month of arrears increases tenant debt levels and further reduces landlord income. In many cases landlords rely on this income to support their living expenses or service a mortgage. The changes are only temporary and there is great concern as to what will happen when the ban is lifted. Some believe that there will be no markable increase in the number of evictions, others belief that there will be a significant increase leading to many tenants being made homeless. While the truth is likely to be somewhere in between, policy makers, service providers and charities urgently need a more detailed understanding of what is likely to happen, to allow them to create policies that minimise the impacts of the ban when it comes to an end. To obtain this understanding we need to identify the extent of the problem as it stands, specifically, how many landlords have arrears and how large are the arrears? We also need to gain insights into how landlords are currently dealing with arrears, to identify how familiar landlords are with the temporary changes in legislation, and to ascertain whether the support currently available, such a loan schemes, is fit for purpose. Insight into the resilience of landlords and identification of the tipping points that may result in an increase in evictions is also necessary, as is the identification of landlord intentions following the cessation of the ban. Unfortunately, we do not currently know the answers to these questions. In fact, we know very little about the behaviours or intentions of landlords in general. This research therefore aims to answer these questions by undertaking primary research with the support of landlords.The research will take the form of a quantitatively focused online questionnaire, which will be issued to a large population of Scottish Private Rented Sector (SPRS) landlords via our project partner SafeDeposits Scotland. The responses from the survey will be analysed and findings generated. The findings will then be shared directly with Government, Parliament, Service Providers and Third Sector organisations. To maximise impact and reach, the findings will be also be made available through a series of blogs and tweets. The entire research process from survey design to the dissemination of the findings will take just 4 months. This accelerated program is required to allow those receiving the data sufficient time to digest the findings and generate appropriate policies in response.",2021,-99,University of Glasgow,35710.72,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C14356,ES/W00299X/1,Assessing Mechanisms for Delivery of COVID-19 Vaccines to University Students,"Achieving a high level of vaccine coverage and immunity among university students is urgent and critical for the long-term control of COVID-19 infections. Mixed methodologies will be used to survey university students' attitudes to COVID-19 vaccination as part of a strategy to develop informed recommendations on university involvement in vaccine programmes. Multiple studies indicate that students are high-risk spreaders of COVID-19 with students' arrival on campus in the autumn of 2020 likely to have contributed to the second wave of the pandemic in the UK. With universities being a major industry, effective delivery of vaccines to students is essential for the inter-twined goals of economic recovery and breaking COVID-19 transmission cycles. University student cohorts are ethnically, economically and geographically diverse with international students being a major, economically-important sub-set of the student population. Delivery of effective student-centred COVID-19 vaccine campaigns will require a clear understanding of how these different student groups perceive the vaccines and whether differing experiences during the pandemic will negatively or positively impact on decisions relating to vaccine uptake. The University of Leicester (UoL) provides an ideal case study. One reason is because UoL is located in one of the cities worst affected by COVID-19. But more importantly, UoL has an exceptionally diverse student population with ~50% having BAME backgrounds and boasts a vibrant international student community. We aim to deliver a vaccine-focussed questionnaire to a large-proportion of the current UoL student cohort whilst making sure of representative coverage of a range of home and international students. We will then conduct 40-80 follow-up semi-structured interviews with specific sub-groups. One set of survey questions will focus on knowledge of the effectiveness and accessibility of COVID-19 vaccines and, as comparators, vaccines that are critical for protection against meningitis, measles and mumps. Another set of questions will focus on vaccine complacency and hesitancy. As a younger age group, students may be less inclined to take up vaccines because of perceptions of a lower risk of falling seriously ill with COVID-19. Moreover, as digital natives, students are comparatively more likely to be exposed to disinformation about COVID-19 vaccines circulating on social media, such as the myth that vaccination leads to female infertility. A final question set and the interviews will examine pandemic experiences. These aspects will focus on COVID-19-related discrimination based on race and ethnicity or prejudice encountered purely on the basis of being a student in a university town, along with the detrimental impact of prolonged lockdowns on wellbeing and individual freedom. There will also be interview questions about students' exposure to media coverage of the pandemic. These factors may all shape students' evaluation of COVID-19 vaccination as a way of returning to 'normal', pre-pandemic life. As an inherently mobile and transient population, university students may be among the hard-to-reach groups for COVID-19 vaccination programmes. In consultation with Public Health England and other stakeholders, we will utilise evidence from our questionnaires and interviews to develop COVID-19 vaccine-delivery recommendations that will be applicable across the entire university sector. The applicability of our ideas will be further explored in a follow-on ESRC application for a multi-partner, multi-institutional project to evaluate COVID-19 vaccine uptake and delivery mechanisms among different student groups and a range of institutions (i.e. universities of differing sizes, types and parts of the country). This application will also address the important long-term goal of developing effective policies on vaccine delivery to undergraduate students that are achievable by all higher educational institutions.",2021,-99,University of Leicester,78517.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts, +C14357,ES/W003333/1,Listen to us! The psychosocial impact of COVID-19 on adolescents - A mixed methods study,"The continued impact of COVID-19 on adolescent mental health, educational attainment and future prospects is of great concern. The aim of our proposed study is to capture the experiences of adolescents as the pandemic unfolds and longer-term societal and economic consequences emerge. Adolescents may be of particular risk for adverse effects due to COVID-19 as this is a period of increased risk for developing psychopathology (Fairchild 2011, Paus et al 2008), as well as a crucial time for establishing personal identity/independence. During this period, peer relationships are especially important (Albarello et al 2018, Hay & Ashman 2003, Steinberg & Morris 2001). Hence, the normal developmental processes of adolescence are likely to be disrupted by the COVID-19 pandemic. Nonetheless, there are individual differences in responses to adversity so that not all individuals exposed to the same stressors will experience adverse effects or impaired mental health (Cicchetti 2010) and some exhibit better-than-expected responses to adversity, a phenomenon known as 'resilience' (Galatzer-Levy et al 2018, Masten 2011, Yule et al 2019). This study has been designed to explore which factors (e.g., gender, ethnicity, socioeconomic status, family function, decision-making abilities) determine the impact of the pandemic on young adolescents. The basis for this work was established just over a year ago when we conducted an online survey to examine the impact of Covid-19 on young people aged 13-24 (n = 2002, stratified by age, ethnicity and deprivation index) as part of the COVID-19 Research Consortium Study (C19PRC, https://osf.io/v2zur/wiki/home/). Our findings revealed unique challenges faced by younger adolescents in terms of the impact of the pandemic on their mental health and highlighted the importance of key factors that are not currently being addressed, e.g., young people's social and psychological adjustment and difficulty in enacting health behaviours (Levita et al 2020a, Levita et al 2020b). Due to a lack of resources, this study did not include follow-ups or further exploration of the lived experience of the pandemic from young people themselves. Consequently, our objective is now to build on this work and enrich the self-report data to more accurately profile the mental health and well-being of adolescents, by following a representative sub-sample aged 13-16 from our original cohort one year on. To that end, we will (1) conduct qualitative individual personal interviews (virtually) with participants. This is a more personal form of research that helps to better explore and understand participants' opinions, behaviour, and experiences and has been missing from research on the Impact of COVID-19 on young adolescents (e.g., Ares et al 2021, Copeland et al 2021, Hawes et al 2021). (2) We will gather mental health, well-being, and resilience indices from an online survey. (3) We will capture, using short smartphone tasks, decision-making indices, that can provide an accurate way (less prone to bias) to gauge how mood affects the way these young people make decisions about risk. These tasks have been shown by our team to predict anxiety symptoms and real-time COVID-19 health behaviours (including social distancing adherence) in adults (Lloyd et al 2020). This work is both timely and urgent, as pupils have now returned to school following the latest lockdown, and we wish to capture both their recent experiences of the lockdown and their current experiences of returning to school. This time period is the last opportunity to capture data at a critical time point before the start of the next school year. In a rapidly changing context, this work will help policy makers understand, from young people's perspective, which groups of young people need support to aid their well-being; when they need support and what kind of support they would like, from evidence-based research.",2021,-99,University of Sheffield,75822.08,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14358,MC_PC_20059,Phase 1 COVID-19 Longitudinal Health and Wealth - National Core Study (Phase 1 LHW-NCS),"The Longitudinal Health and Wellbeing National Core Study will improve understanding of COVID-19 infection risk factors, examine the physical and mental health consequences of asymptomatic to hospitalised cases, and assess the impact of population scale mitigation policy. We will unite distinct, but complementary, longitudinal studies already engaged in COVID-19 research, including UK representative population and hospitalised cohorts, household panel surveys, and national primary care registries. These will be enriched with health and administrative data linkage. Linkage, self-reporting and repeat serological assessment will allow greater precision in case assignment. This collective resource will be mined by a consortium of experienced analysts linked to these resources to provide rapid answers to existing and emerging priority research questions. These include physical and mental health impacts and socioeconomic adversity of those who have had COVID-19 infection, evolving impacts on health and socioeconomic inequalities, and uptake, safety and effectiveness of vaccination and determinants of responses. Our outputs will include briefing notes as well as scientific reports in order to optimise policy influence. Phase 1 funding will: 1. Establish a centralised, responsive resource linking data assets from a diverse range of longitudinal population studies with health, social and environmental records, with harmonised governance for processing and research interrogation. 2. Inform population health and social policy by providing evidence, both proactively and in response to customers, of the medium to long term consequences of infection, and of policies to control the pandemic 3. Establish a cadre of highly skilled big data scientists",2021,2022,University College London,11614720,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts | Economic impacts,2021 +C14359,MC_PC_21006,COVID-19 therapeutics and beyond: An HTS to identify inhibitors of SARS-CoV-2 nsp12 and starting points for other Coronavirus inhibitors,"In the face of rapidly emerging viral pandemics, the normal commercial approach to antiviral translational research will not produce therapeutics in a timely manner. Consequently, there is an urgent need to prepare a strategic resource, openly available, to stimulate research into new antivirals for emerging viruses and, in an emergency situation, to provide compounds for expedited preclinical and human testing. Identification of collections of potent inhibitors of essential viral mechanisms within a virus family provides an excellent starting point for this accelerated transition to preclinical toxicity studies. Ultimately, we envisage libraries of 'poised' anti-coronavirus compounds would enable future responses to emerging pandemics as well as targeting SARS-CoV-2. We believe high throughput screening of a well-curated library enables this, with a focus on identification of robust chemical templates suitable for optimisation. We propose an HTS to identify non-nucleoside small molecules (mwt 200-450 Da) that inhibit the nsp12, the SARS-CoV-2 RdRp. Dependent upon the activity of our molecules, we will test our compounds against other coronavirus replicon systems or infectious virus. The coronavirus polymerase is a druggable antiviral target, conserved across the viral family. SARS-CoV RdRp and SARS-CoV-2 RdRp share a remarkable 96% identity. Morse et al (2020) comment that 'efforts towards drugging coronavirus in a RdRp manner should provide a basis not only to develop therapeutics for 2019-nCoV, but could provide broad-spectrum antivirals useful for future CoV outbreaks'. To that end we expect that classes of inhibitors identified by this proposal will have application across the coronavirus family.",2021,2022,Imperial College London,261209.6,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C14360,MR/V011561/1,Genetic identification of host factors required for SARS-CoV-2 cell infection,"The unprecedented medical and economic impact of the SARS-CoV-2 pandemic represents a global challenge to the scientific community. In the absence of any vaccine or therapeutic agent, it is essential to understand how SARS-CoV-2 interacts with its host cell with the aim of identifying viral vulnerabilities for potential therapeutic intervention. Inhibitors of viral entry have been developed for HIV and HCV and represent an attractive step for therapeutic intervention. In this application we will use our expertise in CRISPR-Cas9 genome-wide forward genetic screens to identify host factors required for virus entry and infection. SARS-CoV-2 cell entry is dependent on its spike protein which mediates both binding to its cognate cell surface receptor, Ace2, and fusion of viral and cellular membranes. The Spike protein is activated by the host cell serine protease TMPRSS2 which promotes viral fusion with the cellular membrane. The role of other host cell proteins in viral entry and infection is less clear, nor do we know how the low oxygen tension of COVID19-infected lungs, affects viral infection. We have developed different models of virus entry, including internalisation of Spike fusion protein, Spike protein pseudovirus infection and, infection with live SARS-CoV-2 virus. Using these tools we will perform genome-wide forward genetic screens to identify host factors required for (i) the regulation of cell surface Ace2 expression; (ii) entry of SARS-CoV-2 into the cell and whether this is affected by low oxygen tension. (iii) Having identified the host factors required for SARS-CoV-2-mediated entry we will validate our results in the context of SARS-CoV-2 infection of primary human bronchial epithelial cells. We will characterise our hits and determine their therapeutic potential. We anticipate that the comprehensive identification of host cell factors essential for SARS-CoV-2 infection will identify targets for the development of novel antiviral agents.",2021,2023,University of Cambridge,569696,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C14361,MR/V01157X/1,MOLECULAR BARRIERS TO THE EMERGENCE OF CORONAVIRUSES IN HUMANS,"We hypothesise that certain circulating bat coronaviruses (CoVs) could emerge in human populations with devastating consequences (similar to SARS-CoV-2). However, the existing human CoVs all appear to have emerged via transmission from possible intermediate species, rather than directly from bats, suggesting that specific molecular barriers may hinder direct zoonotic transmission from bats to humans. We therefore aim to identify both the bat CoVs with increased risk of emerging in humans, as well as genome-encoded defences that could constrain CoV cross-species transmission.By combining supervised machine learning with evolutionary and bioinformatic analyses, we will identify bat CoVs with an increased risk of emergence in humans. Six of these 'poised' bat CoVs will then be synthesised, and combined with highly pathogenic human CoVs, and seasonal human CoVs, to create a cross-species CoV test panel, on which we will focus further molecular experimentation.Previous studies have shown that genome-encoded antiviral defences can form powerful barriers to cross-species transmission of viruses, and are often encoded by interferon-stimulated genes (ISGs). We will therefore define the interferome of horseshoe bats (the reservoir of SARS-CoVs) and construct a library of ~150 horseshoe bat ISGs. These bat ISGs, along with our existing ISG libraries (human, macaque, bovine) will then be used to identify ISGs that inhibit any coronaviruses in our cross-species test panel (described above).Subsequent analyses will examine patterns of restriction of the anti-CoV ISGs in potential intermediate species, in order to identify blocks to cross-species transmission. Together, this knowledge should improve our capacity to make predictions about which CoVs are likely to make successful cross-species 'jumps', aiding surveillance of CoVs with pandemic potential. In addition, understanding how ISGs inhibit CoVs could potentially improve our understanding of SARS-CoV-2 pathogenesis.",2021,2023,University of Glasgow,783390.72,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2020 +C14362,MR/V014919/1,Developing an mHealth intervention to strengthen the community mental health system in the context of the COVID-19 pandemic in Peru,"The COVID-19 pandemic and the mandatory social distancing have made visible the challenges the Peruvian health system faces to provide remote care. People with mental disorders are particularly vulnerable in this context, due to the impact of the pandemic on their health, as well as the limitations in accessing services. As a result, the Ministry of Health in Peru published guidelines to providing mental health care through telemedicine. In this context, which is simultaneously a great challenge and opportunity for the community mental health system in Peru, we proposed a two-year project with the following objectives: (1) To assess the impact of the pandemic on the community mental health system in Peru, (2) To identify the strategies implemented to preserve the provision of mental health care during the pandemic and assess, using the Learning Health Systems framework, the readiness to deliver remote mental care, (3) To co-design and evaluate the performance of an mHealth intervention to deliver remote care within the community mental health system in Peru. To achieve this, the study comprises 3 phases: (1) the formative phase, centered around the first two aims, will involve the review of local and international guidelines and evidence produced during the pandemic and a qualitative study with stakeholders. (2) The intervention development phase to co-design along with stakeholders the mHealth intervention based on the formative phase. Finally, (3) the pilot of our intervention, assessing implementation and clinical outcomes. The pilot will recruit 60 participants (30 users and 30 relatives) who will receive the intervention delivered by 15 health providers. Recruitment will take place at 3 Community Mental Health Centers. Data will be collected at 3 different time points: (i) before starting, (ii) during and (iii) after finishing the intervention, through questionnaires, in-depth interviews, as well as data generated through the mHealth platform.",2021,2022,Peruvian University Cayetano Heredia,258944,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Peru,Peru,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C14363,MR/V028839/1,Developing mass spectrometry to understand molecular mechanisms of antibacterial and antiviral drugs,"The search for new antibiotcs has become more acute as the COVID-19 pandemic has brought a surge in antimicrobial usage that is expected to drive up resistance. Here, we seek to uncover the targets and mechanisms of action of antibiotics and antivirals - aspects that remain, for many drugs, poorly understood or completely unknown. To investigate the mechanisms of action of antibiotics - both new and re-engineered - we have assembled a series of mass spectrometry-based assays, involving in vitro synthesis of bacterial cell-wall components and a clear indication of bacterial lipid flippase activity. Where targets are unknown, we will eject complexes directly from bacterial membranes, monitoring antibiotic responses over time and thereby identifying targets in situ. We also aim to identify new antibiotic targets, by establishing a mechanistic understanding of the membrane-embedded enzymes and multiprotein complexes responsible for remodelling and synthesising components of bacterial cell envelopes. Though extremely difficult to study via standard biophysical approaches, these enzymes and complexes are essential for bacterial survival; a better understanding of them will be invaluable for antibiotic targeting. For our COVID-19 research theme, we will continue our studies with existing antivirals, covering additional drugs that have shown activity in in vitro assays of virus proliferation. Probing interactions among the SARS CoV-2 main proteins, RNA and accessory factors - and, applying our expertise in membrane protein-lipid interactions, we will explore emerging COVID-19 targets, such as the two-pore cation channel in the lysosomal degradation pathway. Bringing antibacterial and antiviral studies together allows synergistic discoveries and consideration of repurposed drugs active in both scenarios, and enables us to contribute to tackling the biggest global health challenges of our time.",2021,2026,University of Oxford,575598.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +C14364,MR/V029339/1,Rapid knowledge mobilisation to promote adolescent mental health in the era of COVID-19,"During the COVID-19 pandemic young people have been exposed to established risk factors for psychopathology and have been struggling to access support from schools and CAMHS. Existing psycho-educational materials typically targeted parents to deliver support to their children or adolescents. This passive transfer of information is unlikely to work well with older adolescents (14-24 years), who progressively separate from their parents and strive to gain agency. To support young people's mental health, we will co-produce novel, engaging psycho-educational materials with adolescents and creative professionals, and rapidly disseminate them widely across the UK. First, we will capitalise on the wealth of data emerging from ongoing longitudinal surveys to capture young people's voices about their mental health concerns and on our expertise in identifying and delivering evidence-based interventions. Second, we will work with young people to prioritise the mental health concerns and to ensure that the content built from evidence-based interventions is clear and relevant. We will then work with young people and creative professionals to produce the materials in the most engaging way. Third, we will disseminate the materials produced widely thought social media campaigns and our established links with voluntary organisations across the UK. The materials will also be disseminated across all devolved nations in partnership with local senior clinicians.",2021,2021,King's College London,257719.04,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C14365,MR/V035924/1,Healthcare and Socio-economic Impacts of COVID-19 on Patients with Diabetes in Tanzania and Kenya,"This project will provide much-needed, timely and unique evidence from rural and urban areas of neighbouring East African Countries (Tanzania and Kenya) with different approaches to the control of COVID-19. The project aims to explore the experiences of people with type 2 diabetes (T2D) and healthcare providers on managing T2D during COVID-19. Guided by the World Health Organization Social Determinants of Health and Wellbeing Framework [1] , it will focus on how the pandemic has impacted patients' and healthcare providers' ability to manage T2D, the socio-economic burden of T2D, and patients' response to COVID-19 itself. It will also identify policy gaps in each country in relation to health and social care of T2D during COVID-19. The study will foster multidisciplinary collaboration and capacity building by close working between scientists from Africa and UK throughout delivery of five interrelated workpackages (WPs). WP1 will employ questionnaires (N=500 in each country) and in-depth interviews (N=30 in each country) to explore patients' experiences of healthcare access, and T2D self-management, socio-economic challenges and knowledge, attitude and practices related to COVID-19 in rural and urban settings in each country. WP2 will use a desk review and field research to estimate the individual and societal economic burden of T2D. In WP3, IDIs with local healthcare providers (N=15 in each country) will explore their perspectives on T2D management during COVID-19. In WP4, a policy landscape analysis in each country will employ a desk review and key informant interviews to identify policy gaps, priority setting and action for T2D during COVID-19. WP5 will use a multi-stage participatory process involving key stakeholders in which evidence from WPs 1-4 will be synthesised to develop context-specific national policy recommendations and health education messages for T2D management during COVID-19",2021,2023,Ifakara Health Institute (IHI),569109.76,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Other,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Tanzania,Tanzania | Kenya,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Social impacts | Economic impacts | Policy research and interventions,2021 +C14366,MR/V036939/1,REBRACOVID' - multicentre cohort study of the natural history and immunology of COVID-19 in Brazil,"While a number of COVID-19 cohort disease demographic and mechanism studies are in progress, many unknowns remain, and each setting has offered distinctive insights. The clinical imperative to better understand the specific challenges in Brazil is strong: WHO data places Brazil 2nd in the world for COVID-19 cases and deaths. Furthermore, this huge country poses challenges of urban crowding and socioeconomic disparities and a healthcare system stretched by disease burden. On a COVID-19 disease trajectory lagging about 1-month behind Europe, there is potential to establish a large cohort during acute disease, taking into account mechanistic insights already gained. In doing so, we benefit also from building a consortium that bolts-on to our established consortium, international,collaborative studies, REPLICK (Brazil) and SPIICA (Anglo-Brazil, MRCNewton ref MR/S019553/1), designed to conduct analogous cohort studies in relation to the immunopathology and chronic disease phenotype in Chikungunya virus infection. We aim to recruit a cohort of 20,000 total infected, PCR+ COVID-19 cases from 9 centres across Brazil, as well as household contacts and healthcare workers. We will characterise basic demographics of those affected, including impacts of age, gender, occupation, ethnicity, co-morbidities, socio-economic factors, blood biochemistry, antibody and T cell immunity (and durability), CT findings, as well as defining chronic sequelae. We will also investigate treatment modalities and co-infections in relation to disease outcome. Communication of findings from this cohort study will be valuable to inform management of the pandemic in Brazil and elsewhere.",2021,2022,Imperial College London,642785.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences",2020 +C14367,MR/V040049/1,CoV-Ind-UK: Prospective investigation of the determinants for COVID-19 outcomes amongst South Asians in India and the United Kingdom.,"South Asian people are at high risk both for infection with SARS-CoV2 virus, and for developing severe or fatal COVID-19. Addressing this inequality is a major public health priority. In this study, we will identify incident COVID-19, amongst ~30,000 South Asian men and women who are participants of our established prospective population studies in India and the UK. Participants will undergo testing for SARS-CoV2, and complete a validated questionnaire to assess symptoms, relevant behaviours, attitudes to vaccination, and adverse outcomes. We will use our available comprehensive baseline phenotypic data, including molecular characterisation and stored biological samples, collected before the COVID-19 pandemic, to determine what are the major risk factors for infection with SARS-CoV2, severe COVID-19, or prolonged COVID-19, amongst South Asians in India and the UK. We will focus initially on recognised risk factors such as adiposity, raised blood pressure, diabetes, cardiovascular disease, health behaviours, socio-economic indicators, and biochemical measures. We will compare our results in South Asians with equivalent data for Europeans, to determine whether these known risk factors explain the high risk of COVID-19 in Asians. We will develop simple tools for predicting risk of COVID-19 in South Asians, that can prioritise people for vaccination or behavioural interventions, and thus protect them from COVID-19. We will report on vaccine hesitancy in South Asians and the main reasons for this. Finally, we will use 'all-of-the-data', including available health and genetic data, to search for novel risk factors or biological processes that might contribute to COVID-19 in South Asians. Our research will thereby determine the reasons underlying the high burden of COVID-19 in South Asians and generate knowledge that will inform health policy and practice for prevention and control of the disease amongst South Asians in India, the UK and globally.",2021,2022,Imperial College London,1240849.92,Human Populations,Asian | Other,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,India | United Kingdom,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Vaccine/Therapeutic/ treatment hesitancy",2021 +C14368,MR/V040162/1,CARDINNATE: Variation in innate immune activation and cardiovascular disease risk as drivers of COVID19 outcome in South Asians in UK and India,"In the UK, individuals of South Asian heritage have a higher COVID-19 mortality rate than other ethnic groups, even after adjusting for age and social., , factors. This is driven by a greater risk of in-hospital death rather than an increased rate of admissions, in part related to a higher prevalence of cardiovascular disease (CVD) and diabetes which are recognised risk factors for severe COVID-19. By contrast, mortality rates for COVID-19 in India are markedly lower than the UK. Severe COVID-19 is associated with profound systemic immune dysregulation, haemodynamic and thrombotic complications. Multiple lines of evidence suggest that innate immune mechanisms, specifically variation in the regulation of the type 1 interferon (IFN) response and the subsequent dysregulation of cellular innate and adaptive immunity, may be very important determining factors in COVID-19 pathogenesis. Hence these mechanisms are good candidates for underlying increased mortality risk in UK South Asians and set a platform for understanding why the situation is different in India. Our multi-disciplinary UK and India team will elucidate the inter-relationship among innate immune mechanisms, pre-existing CVD/diabetes and environment (India versus UK). Differences in innate immunity, which provides a first line of defence to infection, are captured by the term ""trained immunity"", reflecting its conditioning in part via IFN, by exposure to endemic environmental pathogens, diet, and inflammatory conditions including CVD/diabetes. Hence, evident differences in these factors for South Asians in India versus the UK may profoundly affect the speed and strength of first-phase immune responses to SARS CoV2, as well as attendant cardiovascular damage and dysfunction, to collectively drive systemic immunopathology and the differences in COVID-19 mortality between the UK and India.",2021,2022,King's College London,1293423.36,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,India | United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C14369,MR/V040170/1,Role of the oral microbiome & mucosal immunity in COVID-19 disease: diagnostic/prognostic utility in South Asian populations,"SARS-CoV2 (CoV2) primarily infects respiratory mucosae, yet the role of mucosal immunity is not known. UK South Asian (SA) patients have a higher mortality from CoV2 infection than most ethnic groups, whereas in India similarly adjusted mortality rates are lower than in the UK. We hypothesise that mucosal immunity plays a role in susceptibility to and severity of COVID-19 and explains these differences. Minor salivary glands appear to be major sites of CoV2 replication leading to extremely high viral counts in saliva and upregulated production of cytokines. Mucosal surfaces have their own microbiome which protects against pathogens and oral, lung & nasal microbiomes are closely related. Microbiome dysbiosis may be a factor in COVID-19 severity. This study will therefore compare the oral microbiome, salivary innate and specific mucosal antibody responses longitudinally among CoV2-positive SA patients in India and the UK and determine their diagnostic and prognostic utility.Healthy controls and CoV2-positive patients of SA origin with asymptomatic or symptomatic disease or who are COVID recovered will be recruited in the UK and India. Blood and stimulated whole mouth saliva (SWMF) samples will be collected longitudinally for up to 90 days from infected individuals. Cytokines, T cell phenotypes and IgA & IgG anti-CoV2 antibodies will be determined in SWMF and compared with those in blood. The SWMF microbiome will be analysed by shotgun metagenomics and the metabolome by using NMR. The influence of pre-existing mouth disease in susceptibility to COVID will be determined. Identification of these factors should result in direct and applicable clinical benefit to SA populations and others. Ongoing collaborations between London and Chennai will facilitate commencement of these studies. In London, samples will be taken from patients who are also part of a partner proposal (KCL-SIMS), enabling saving on research costs.",2021,2022,King's College London,560357.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,India | United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity,2021 +C14370,MR/V040235/1,Explaining the differential severity of COVID-19 between Indians in India and the UK,"Emerging data suggest that Indian residents may be less susceptible to severe COVID-19 than Indians in the diaspora. It remains unclear whether these differences are real or due to data artefact. Hypothesized mechanisms for protection from COVID-19 include lower burden of obesity and cardio-metabolic disease, greater exposure to vitamin D, and cross-immunity from past infections and vaccinations. The aim of this study is to determine whether the risk of severe COVID-19 (defined as COVID-19 related hospitalisation or death) differs between Indian populations in India and the UK and the extent to which this is explained by differences in data quality, age structure, co-morbidities, and cross-immunity. This project will comprise two work packages: The first is an epidemiological study comparing the population prevalence of severe COVID-19 in India and the UK. Using anonymised longitudinal electronic health record data for 400,000 people of Indian ethnicity in the UK, we will quantify the prevalence of severe COVID-19 adjusted for age, sex, and co-morbidities. A parallel analysis will be conducted in India using COVID-19 surveillance and chronic disease registry data from 220,000 people in the extended cohorts of two established studies in the states of Karnataka and Telangana. The second work package will use detailed biomarker and phenotyping data available in a 10,000 person subset of the two Indian cohorts to conduct an in-depth mechanistic study to elucidate hypothesized relationships between COVID-19 severity, environmental (vitamin D levels) and socio-economic factors (cross-immunity from greater exposure to infections and lower rates of obesity and cardiometabolic co-morbidities due to undernutrition). Findings will be used to triangulate evidence on the differential severity of COVID-19 in global Indian populations and translated into recommendations for clinical and policy use targeted at reducing risk of severe COVID-19 in Indian populations worldwide.",2021,2022,London School of Hygiene & Tropical Medicine,354237.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe | South-East Asia,,,,United Kingdom,India | United Kingdom,Epidemiological studies,Disease susceptibility,2021 +C14371,MR/W000970/1,Longitudinal immune and inflammatory responses in the respiratory mucosa and blood of patients after hospitalisation with COVID-19.,"This study will test the hypothesis that natural infection with SARS-CoV-2 results in virus-specific IgA and T cell responses in the nasal mucosa, which are sustained for up to one year.In order to study the longevity of immune responses, 400 participants who have been hospitalized with COVID-19 will have blood and nasal samples collected at 3, 6 and 12 months post-discharge.Nasosorption allows collection of concentrated nasal fluid which is amenable to studies of antibody specificity. ELISA will be used to determine mIgA/IgG titres at each time-point to longitudinally assess the mucosal antibody response. Responses to viral epitopes including spike and nucleocapsid will be measured. Participant vaccination status and timing will be recorded during the study. This will allow comparison of spike and non-spike antibody titres following vaccination in order to compare the course of natural immunity and vaccine boosted immunity. This will also identify if vaccination can boost mucosal immune responses to SARS-CoV-2. MHC Tetramer staining on nasal curette samples will be used to analyse virus-specific tissue resident CD8+ and CD4+ T cell responses. This will be assessed at each time point to determine the strength and durability of responses. Cytokine levels in plasma and nasal mucosa will be measured through multiplex ELISA. This will be related to data from flow cytometry in selected patients, characterising neutrophil and NK cell populations in the blood and nasal mucosa. This will enable study of the chronic inflammatory response in those with symptoms of Long COVID.This is the first study to provide insights into long-term mucosal antibody and T cell responses to SARS-CoV-2 in convalescent patients. This study will identify if mucosal responses are a potential correlate of protection which can be evaluated further in mechanistic studies. This has important implications for vaccine development and understanding the future course of the pandemic.",2021,2024,Imperial College London,312268.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C14372,MR/W014556/1,The cellular immune response to B.1.1.7 variant COVID-19 deciphered by single cell multi-omics,"During wave 1 of COVID-19, we performed the largest single cell multi-omic analysis of peripheral blood cells from 130 COVID-19 patients and controls, measuring full transcriptomes, 192 proteins and B-cell/T-cell receptor rearrangement status in over 800,000 single cells (https://www.medrxiv.org/content/10.1101/2021.01.13.21249725v1; currently in Minor Revision at Nature Medicine). With over 1,500 individual datapoints for each single cell, our dataset contains in excess of 1 billion total datapoints, and therefore provides the perfect reference to ask whether COVID-19 caused by the B.1.1.7 variant differs in the way it affects all our blood and immune cells. We have already collected samples from over 30 patients with the new variant, but do not have the funds to carry out the single cell profiling (£30,000 required in total). Experimental and bioinformatics staff will donate their time. All we need is funding to pay for the reagents for single cell genomics (~£1,000 per patient). Given the recent announcements, that the new B.1.1.7 variant strain is likely to cause higher rates of mortality, there is a pressing need to perform the most detailed molecular comparisons possible between patients infected with the old and new strains. The main urgent outcome may be to reassure the medical community and wider public that the molecular profiles of patients are broadly similar, thus confirming that the current treatments are still appropriate for variant B.1.1.7. It is of course also possible, that distinct immune pathways are activated, which will inform the development of new treatment strategies, and would require follow-on funding.",2021,2021,University of Cambridge,47744,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +C14373,MR/W015560/1,MICA: Pharmacokinetic/Pharmacodynamic (PKPD) Model Development to Inform SARS-CoV-2 Antiviral Development,"Antivirals generally need to reduce viral load to positively influence clinical endpoints such as hospitalisation or mortality. To prioritise antivirals for Phase III trials, Phase II trials seeking significant viral load decrease versus placebo are required. Interpreting viral load is challenging since it changes with time since infection (rises then falls) and by sampling site. This proposal seeks to develop a pharmacometric nonlinear mixed effects model of SARS-CoV-2 viral dynamics. The model will be used to design and analyse efficient antiviral Phase II trials, and prioritise antivirals and antiviral combinations for Phase III. The target cell limited model, along with its common extensions (eclipse phase and innate and adaptive immune components) and simplifications (quasi-steady-state assumption between infected cell and free virus numbers), will be compared using graphical and numerical model diagnostics. A preferred model will be chosen and applied to viral load data in ongoing trials and to simulate outcomes to optimally design future trials. The model will be applied to real-world clinical data to seek subgroups of hospitalised patients who may benefit from antivirals. It will also be used to perform a model-based appraisal of whole genome sequence-derived biomarkers such as subgenomic RNA, to be assessed as a possible Phase II endpoint. This work will be carried out by a collaboration of academic, clinical and pharmaceutical industry investigators who will develop and share SARS-CoV-2 antiviral modelling best practice.",2021,2022,University College London,302279.68,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Therapeutic trial design,2021 +C14374,MR/W01615X/1,CHEKOV: CHEcKpoint Inhibitor effects On SARS-CoV-2 Vaccination,"Data on the effectiveness of prophylactic vaccination in cancer patients is limited. Patients receiving Immune Checkpoint Inhibitors (ICIs) are likely to differ from other groups due to the unique mode of action of these agents: blocking homeostatic controls that normally limit T-cell response generation and effector functions, which include direct cytotoxicity but also providing B-cell help essential for establishing effective antibody responses. It is unknown whether ICI-exposure affects the size and quality of the T-cell/antibody response to SARS-CoV-2 infection and vaccination, possibly skewing them away from virus control to enhance immune pathology, and, conversely, whether virus infection alters ICI-induced immunity including patterns associated with auto-immunity. We will describe the immune interactions between ICI treatment and immunity to SARS-CoV-2 infection and vaccination using an already established blood sample collection from well-defined cohorts including: i) healthy donors pre- and post-vaccine, ii) serial samples from people with melanoma (with linked clinical data) receiving ICIs pre- and post-vaccine, and iii) melanoma patients infected with SARS-CoV-2 while treated with ICIs. We will first measure IgG, IgA and neutralising antibody responses to spike and nucleocapsid antigens using MesoScale assays. This will provide a rapid initial assessment of vaccine efficacy in patients. We will then characterise T-cell responses to overlapping peptide pools spanning the open reading frames of the main virally encoded T-cell antigens (spike, nucleocapsid and matrix proteins) using an established intracellular cytokine assay capable of measuring six effector functions (IFN-g, TNF-a, IL-4, IL-10, IL-17, and cytotoxic degranulation by surface exposure of CD107a) on CD8+ and CD4+ T-cells.",2021,2021,University of Birmingham,71127.04,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C14375,MR/W01730X/1,Functional immune responses after the use of immune-modulatory therapy for Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV2 (PIMS-TS),"During the first few months of the SARS-CoV2 pandemic, a new paediatric syndrome was described: Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV2 (PIMS-TS), whereby children presented with fever and multisystem inflammation ranging from mild symptoms to critical illness with multi-organ failure. For mild cases supportive treatment appears to be sufficient, however more severe cases have been treated with a range of immune-modulators including intravenous immunoglobulin, systemic glucocorticoids, tumour-necrosis-factor blockade, interleukin-6 and/or interleukin-1Ra inhibitors. Although largely effective in reducing the inflammation and resolving acute cardiovascular impairment, the medium and long-term outcomes of the use of these therapies is not well-described, and there is clinical equipoise about which agent is most best-suited to treat future cases of PIMS-TS. In addition PIMS-TS/COVID in itself may have medium/long lasting impact on the immune system. An improved understanding of the extent and duration of immune-suppression caused by the immune-modulatory agents used to treat PIMS-TS will help guide clinicians to appropriate follow-up, further investigations and potentially interventions such as vaccine boosters, shielding or even the use of antimicrobial prophylaxis. It may also help to differentiate between different agents and their medium-long term impact on the child's immune system, and this may inform treatment strategies. The three main paediatric centres for the management of PIMS-TS in London are: Great Ormond Street Hospital, Evelina Children's Hospital and St Mary's Hospital, and this study proposes to recruit children from these centres to examine the functional immune responses during the recovery from PIMS-TS and following their treatment with immune-modulatory therapy.",2021,2021,Imperial College London,19299.84,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management",2021 +C14376,MR/W020556/1,Determining the immunological basis for weakened SARS-CoV-2 vaccination outcomes,"COVID-19 vaccine efficacy in people living with HIV (PLWH) and other immunosuppressive conditions such as B cell malignancies remains poorly evaluated. The objective of this study is to establish the quality and durability of responses to inform future recommendations/policy. Optimisation of vaccine responses will maximise protection against disease and new emerging variants in this vulnerable population. In this study we will use our combined expertise and well curated longitudinal cohorts of clinical samples to: 1. Perform an integrated analysis of innate and adaptive components of the immune responses and dynamic changes post vaccination to allow stratification of functional anti-SARS-CoV-2 responses regardless of clinical drivers. 2. Determine mechanistically why these inferior responses occur by testing the hypothesis that breadth is limited by inefficient B cell recall (assessed by BCR sequencing of spike-reactive B cells) due to sub-optimal T cell help and/or excessive NK cell regulation. To achieve these aims we have available samples pre and post vaccination from a well-characterised longitudinal cohort of HIV negative (n>100), PLWH) (n>100), and patients with B cell malignancies (n>70). In addition, we are uniquely placed to sample additional PLWH with suboptimal responses to vaccination through the current SARS-CoV-2 seroprevalance study (>1500 participants). Our approach is to investigate extreme ends of the immunosuppression spectrum by investigating mild to severe T cell impairment (PLWH) and major B cell dysfunction during malignancy. This will yield data to allow informed vaccination choices/boosters based on immunological phenotype rather than clinical presentation, facilitating translation of these results beyond the study populations.",2021,2022,University College London,544133.12,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR) | UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C14377,MR/W020564/1,SARS COV2 vaccine ResPonse In Obesity - SCORPIO study,"Over 20% of the UK population are obese; people with obesity have substantially higher morbidity and mortality from COVID-19 infection. As obese people have reduced immune responses to other vaccines (influenza, hepatitis), we hypothesise that obesity may similarly reduce the protection offered by SARS-CoV-2 vaccines by impairing cellular immunity, reducing initial antibody titres and/or by causing an acceleration of the natural decline in antibody titres. We will address this question by recruiting a cohort of 200 patients with severe obesity (Body Mass Index (BMI)>40 kg/m2) - the population we suspect is at highest risk - from clinics in Cambridge University Hospital and Kings College Hospital, London (SCORPIO study). We will compare their vaccine responses (T and B cell-mediated immunity, neutralisation assay, anti-Spike and Nucleocapsid antibodies, inflammatory cytokines) to 1500 normal weight people studied using the same assays. To comprehensively investigate the impact on vaccine responses of BMI across the full range from overweight, to obese and severely obese, we will collaborate with a network of investigators leading existing UK studies to perform a meta-analysis of 50,000 people. We will seek to identify predictive nutritional and metabolomic biomarkers (obese responders vs non-responders) and test whether weight loss (shown to improve response to the influenza vaccine in mice) can improve vaccine responses in obese people. This ambitious programme of research will deliver new insights into the relationship between BMI, metabolic health and the response to SARS-CoV-2 vaccines and inform public health policy in this area, within 12 months.",2021,2022,University of Cambridge,962936.32,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C14378,MR/W020610/1,The Durability of immune Responses to vaccination against SARS-CoV-2 and its Variants.,"This proposal comes from a team who have been at the forefront of decoding immune parameters in COVID-19 throughout the pandemic, giving us a sharp focus on the current questions. The concern is to understand, at a qualitative and quantitative level, the details of immune response durability in 'real-life settings' of different vaccination regimens, with or without prior infection. We will study large, longitudinal, cohorts (totalling 12097 individuals) with different exposures to SARS-CoV-2 and its variants, in the UK, South Africa and Brazil, enabling us to study vaccination using diverse platforms, with or without infection by SARS-CoV-2 and the alpha, beta, gamma and delta variants of concern (VoC). These are cohorts with a high-granularity history, encompassing infection and symptom history as well as immune data. Moving forward, we wish to understand the durability and nature of immune protection, including susceptibility to reinfection and breakthrough infections. To achieve this, we will track longitudinal immunity, analysing serum antibody durability, live virus neutralisation, antibody affinity, B cell receptor repertoire and B cell memory frequency, both to wild-type and variant targets. In terms of T cell immunity, we will track durability of response frequency to wild-type and variant epitopes using a wide range of approaches. The CLARITY and CML-Co-vax Cohorts will enable us to probe vaccine response impairment and its mitigation in immunosuppressed cohorts (IBD and chronic myelogenous leukemia) after Infliximab or tyrosine kinase inhibitor (TKI) therapy respectively. Data will be modeled in relation to CoP values to extrapolate and provide guidance regarding the need / timing of boosts for different vaccine platforms in healthy adults and immunosuppressed patients to achieve protective immunity.",2021,2022,Imperial College London,1008181.76,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Americas | Europe,,,,United Kingdom,United Kingdom | South Africa | Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation | Health Systems Research","Immunity | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity | Medicines, vaccines & other technologies",2021 +C14379,MR/W020629/1,An immunogenetic approach to guide the need for booster shots and combat immune failure in SARS-CoV-2 vaccine response,"Vaccination has been hugely impactful in control of the current COVID-19 pandemic. However, in a significant proportion of individuals, the immune response to vaccination is insufficient to control SARS-CoV-2 and this may be exacerbated with viral variants of concern. To establish the optimal strategy for booster vaccination, we propose a programme of work that will advance our ability to identify individuals who have, or are at risk of mounting, a low response to COVID-19 vaccination; to understand the underlying heritable, molecular and immunological mechanisms for this response; and whether booster dose vaccination can mitigate a dampened immune response. To deliver this, we propose a collaborative, multi-disciplinary and multi-centre approach. We will work with the National COVID-19 Infection Survey to contact individuals in the general UK population with extremes of antibody responsiveness to vaccination and map genetic associations with response. This will deliver specific predictive genetic biomarkers that can help identify at risk individuals and populations and reveal novel insights into mechanism of poor vaccine response. Complementing this genetic analysis, we will investigate the role of clonal hematopoiesis of indeterminate potential and of epigenetics. We will determine the effect of booster vaccination in poor responders to facilitate multivariate analysis of the immune response and help identify associated immune correlates. The project deliverables will directly impact and inform vaccine policy and rollout.",2021,2022,University of Oxford,1263953.92,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease susceptibility | Characterisation of vaccine-induced immunity,2021 +C14380,MR/W020653/1,Optimising Vaccine Efficacy in Multi-Disease Patient Cohorts with SARS-CoV-2 vaccine failure (OCTAVE-DUO),"The multi-centre OCTAVE study is a flagship UK CTIMP evaluating the immune response following COVID-19 vaccination in people with immune mediated inflammatory diseases, hepatic/gastrointestinal disease, renal failure, solid or blood cancers, solid organ transplant, and patients who have received haematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cells (CAR-T). Uniquely, OCTAVE seeks to comprehensively assess SARS-COV-2 vaccine responses within and between disease cohorts using common platforms in patients recruited across the UK. Early data show that approximately 30% of patients mount a low, or undetectable immune response after two homologous SARS-CoV-2 vaccines evaluated by serology based assays. It is not known whether re-vaccination booster strategies will initiate, or further enhance the immune response to thereby provide appropriate protection from COVID-19 in these prevalent and clinically vulnerable disease cohorts. Leveraging our existing and successful OCTAVE consortium, and its related infrastructure, the OCTAVE-DUO study will investigate the effectiveness of homologous and heterologous re-vaccination strategies using licensed vaccines to generate a protective immune response in patients within our disease cohorts who have sub-optimal primary vaccine responses. Patient will be stratified based on low/no serological vaccine response and state-of-the-art optimised immune assays will characterise the magnitude, functionality, and durability of T cell and humoral immune responses following re-vaccination. NHS data linkage and standard pharmacovigilance approaches will determine the level of protection afforded by revaccination and adverse events related to a third vaccine exposure. Identifying immune and clinical parameters that predict which patient populations will benefit from re-vaccination strategies will critically inform UK health and government policies during the ongoing pandemic.",2021,2022,University of Glasgow,718415.36,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C14381,MR/W02067X/1,Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway,"The SIREN Consortium aims to investigate the correlates of immunity against SARS-CoV-2 post-vaccination, including the durability of the immune response in healthcare workers (HCW). The study uses the strengths of the largest global cohort study (N~45,000) with regular serological and alternate weekly SARS-CoV-2 PCR testing. This additional funding enables detailed immunological nested case-control studies where cases are infections post-vaccination and compared to appropriately matched controls. 75 proven vaccine breakthrough cases have already been identified and daily alerts for new infections are in place. It will assess host and pathogen factors related to infections post-vaccination with the PITCH Plus pathway 1. Anti-S and anti-N neutralising antibodies against the current SARS-CoV-2 variants of concern, using validated pseudovirus microneutralisation (pMN) assay and live virus MN & Tcell memory responses, by IFNG Elispot and T cell proliferation assay 2. The durability of binding and quantification S and N antibody, neutralising antibody and T-cell responses in recipients of different vaccines and vaccination schedules 3. Genotype to phenotype mapping including centralised genomic surveillance for all cases, analysis and exploratory assessment to better define the correlates of humoral and cellular immunity for novel mutations/ emerging variants. 4. Clinical immunology consultation: individuals with post-vaccine infections will be invited to a telephone consultation to review their medical history, have bloods undertaken to assess underlying health conditions, associated immunodeficiency and the humoral and cellular immune system. 5. Human genotyping with consent we will obtain and store genetic material from vaccine breakthrough cases to enable future assessment of known single nucleotide polymorphisms and where necessary whole genome sequencing for associations with suboptimal vaccine response and immunodeficiency.",2021,2022,Department of Health and Social Care,2029779.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Characterisation of vaccine-induced immunity",2021 +C14382,MR/W022397/1,Africa CDC - LSHTM MRC International Statistics & Epidemiology Group Partnership to Support Robust Analysis of COVID-19 Seroprevalence Data in Africa,"Africa CDC is coordinating a unique, multi-national research initiative, supporting African Union Member States to carry out robust nationally-representative COVID-19 seroprevalence surveys, in order to inform rapid response prevention planning, policy, and practice at country and continental level. Seventeen countries joined the first wave of surveys, of which six have completed data collection, and seven are expected to do so by October 2021. Participating countries will analyse their survey findings with support from Africa CDC as needed, and have agreed to share their data for aggregate analysis and interpretation under precedent-setting data-sharing agreements. However, there is currently insufficient statistical and epidemiological capacity to undertake these critical activities. The aim of this proposal is to employ a medical statistician, initially on a six-month basis, to rapidly undertake time-critical analysis of the COVID-19 seroprevalence data, facilitated by Africa CDC, in order to inform policy decisions for pandemic response including vaccine scale-up. The statistician will manage and analyse this complex multi-country survey data, advise country-level teams on survey design and analysis issues, and establish the database for future research. They will provide on-the-job training and mentoring to the Africa CDC epidemiology analytics team and will support strategic interpretation and use of COVID-19 seroprevalence and vaccine coverage data and findings to inform Africa CDC and the Member States in their ongoing COVID-19 response including vaccine roll-out strategies. Following the six-month period, further funding will be identified to extend the duration of the post and to enable sustainable strengthening of biostatistical capacity at Africa CDC.",2021,2022,London School of Hygiene & Tropical Medicine,76225.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +C14383,NE/W00481X/1,Air quality benefits from multi-year changes in post-pandemic working and travel patterns,"Air quality is significantly affected by levels of economic activity and wider patterns of industrial and domestic consumption. Whilst lower air pollution was frequently reported as a short-term consequence of lockdown, less well quantified are the potential longer term improvements in urban air quality that may arise from more sustained shifts in behavioural patterns during the recovery phase and beyond. For example, these may arise from changed commuting modes, office and school times, and continuation of homeworking. Altered air pollution emissions in cities, even if only sustained for a few years, may deliver disproportionately front-loaded benefits. As the UK transitions towards transport electrification and older vehicles leave the fleet, it is in the years immediately following the pandemic that the largest benefits to air quality are likely to be felt. Lower air pollution during the lockdown phase of the pandemic was not surprising, with NO2 falling widely across the UK. More surprising has been the recent divergence between increasing traffic volumes and the rebound in pollution as restrictions on society have lifted. Understanding the mechanisms behind this, and the potential air quality and public health opportunities, lies at the heart of this proposal. This research is ideally conducted at a time once most the significant lockdown restrictions have been lifted and specifically once schools (and their related transport have resumed). It is therefore timed to begin towards the end of 2020. The real-world impacts of this research may be highly significant, allowing an evaluation changing urban emissions regimes.",2021,2022,University of York,229361.92,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C14794,unknown,"PRIMARY CARE OF THE HABITAT IN POPULAR NEIGHBORHOODS OF GRAN LA PLATA, IN THE FACE OF THE HEALTH EMERGENCY OF COVID-19",,2020,-99,CENTRO INTERDISCIPLINARIO DE ESTUDIOS COMPLEJOS - FACULTAD DE ARQUITECTURA Y URBANISMO ? UNIVERSIDAD NACIONAL DE LA PLATA,6019.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14795,unknown,ECONOMIC AND PRODUCTIVE EFFECTS OF SOCIAL ISOLATION ON INDUSTRY SMES AND SERVICES IN THE PROVINCE OF BUENOS AIRES (CONURBANO AND OTHER HIGH DENSITY LOCATIONS INDUSTRIAL),,2020,-99,UNIVERSIDAD NACIONAL DE SAN MARTÇ?N - INSTITUTO DE ALTOS ESTUDIOS SOCIALES,14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14796,unknown,CYT FOR INDUSTRIAL DEVELOPMENT. AN ANALYSIS OF THE HETEROGENEITY OF THE PRODUCTIVE STRUCTURE OF THE PROVINCE OF BUENOS AIRES IN THE FRAMEWORK OF THE COVID-19 PANDEMIC.,,2020,-99,UNIVERSIDAD NACIONAL DE GENERAL SARMIENTO,7200,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14797,unknown,MONITORING AND MONITORING OF STRATEGIES TO MINIMIZE THE CIRCULATION OF COVID 19 IN THE MUNICIPALITY OF GENERAL PUEYRREDÓN,,2020,-99,UNIVERSIDAD NACIONAL DE MAR DEL PLATA - INSTITUTO DE HUMANIDADES Y CIENCIAS SOCIALES (INHUS),4752,Unspecified,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C14798,unknown,DEVELOPMENT OF AN INFORMATION SYSTEM FOR THE RECOGNITION AND MONITORING OF THE RESPONSE AND ORGANIZATION CAPACITIES OF THE SOCIAVULNERABLE COLLECTIVES OF THE MORENO MUNICIPALITY IN THE FACE OF THE COVID19 PANDEMIC,,2020,-99,UNIVERSIDAD NACIONAL DE MORENO,4392,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Social impacts | Systemic/environmental components of capacity strengthening, +C14800,unknown,PEDAGOGICAL CONTINUITY IN TIMES OF PANDEMIC: A STUDY OF DISTANCE EDUCATIONAL MODALITIES AND THEIR IMPACT ON SOCIAL INEQUALITIES IN THE PROVINCE OF BUENOS AIRES.,,2020,-99,UNIVERSIDAD NACIONAL DE LA PLATA - CONICET - CENTRO INTERDISCIPLINARIO DE METODOLOGÇ?A DE CS SOCIALES,6912,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C14801,unknown,"HOUSEHOLD LIVING CONDITIONS AND CARE FACING THE PREVENTIVE AND COMPULSORY SOCIAL ISOLATION BY COVID-19 IN LA PLATA, BERISSO AND ENSENADA. STATUS OF THE SITUATION OF CHILD WELFARE AND PROPOSALS.",,2020,-99,CICPBA - COMISIÇÿN DE INVESTIGACIONES CIENTÇ?FICAS DE LA PROVINCIA DE BUENOS AIRES,5846.4,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14802,unknown,"STRENGTHENING OF FOOD SOCIO-ECONOMIC CIRCUITS, FOR THE ATTENTION OF THE FOOD EMERGENCY FACING COVID-19 IN THE QUILMES AND SURROUNDINGS PARTY",,2020,-99,UNIVERSIDAD NACIONAL DE QUILMES,9504,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C14803,unknown,CONDITIONS AND CONDITIONS OF TEACHING WORK AT THE SECONDARY LEVEL IN CONTEXTS OF PANDEMIC. FROM PRESENTIALITY TO VIRTUALITY FORCED,,2020,-99,UNIVERSIDAD NACIONAL DE GENERAL SARMIENTO,6624,Human Populations | Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14804,unknown,PROVINCIAL PUBLIC COMPANIES AS VECTORS OF DEVELOPMENT AND TECHNOLOGICAL AND PRODUCTIVE SCALING,,2020,-99,UNIVERSIDAD NACIONAL DE QUILMES,13032,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C14805,unknown,EFFECTS OF THE COVID19 CRISIS ON THE LABOR MARKET AND LIVING CONDITIONS OF THE POPULATION IN THE PROVINCE OF BUENOS AIRES,,2020,-99,UNIVERSIDAD NACIONAL DE GENERAL SARMIENTO,3600,Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C14807,unknown,ASSESSMENT AND PERSPECTIVES OF THE MANUFACTURING INDUSTRY IN THE PROVINCE OF BUENOS AIRES POST-COVID19: A STUDY OF THE METALMECHANICS AND CAPITAL GOODS SECTORS WITH A VIEW TO A RECOVERY AND DEVELOPMENT STRATEGY,,2020,-99,UNIVERSIDAD DE BUENOS AIRES,10059.84,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14808,unknown,"INDIGENOUS KNOWLEDGE AND PRACTICES IN A HEALTH EMERGENCY CONTEXT: CONTRIBUTIONS TO HEALTH, EDUCATION AND THE ENVIRONMENT WITHIN THE FRAMEWORK OF THE PLANNING OF CONTROL, PREVENTION AND MONITORING STRATEGIES OF COVID-19",,2020,-99,UNIVERSIDAD NACIONAL DE LA PLATA - FACULTAD DE CIENCIAS NATURALES Y MUSEO,4320,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C14809,unknown,TUTORING THROUGH THE VIRTUAL PLATFORM OF UNIVERSITY STUDENTS TO ELEMENTARY LEVEL STUDENTS OF THE CAMPANA PARTY.,,2020,-99,UNIVERSIDAD TECNOLÇÿGICA NACIONAL ? FACULTAD REGIONAL DELTA,7200,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14810,unknown,"COVID 19: WORK, GENDER AND INEQUALITIES IN THE PROVINCE OF BUENOS AIRES",,2020,-99,UNIVERSIDAD NACIONAL DE J.C. PAZ,14400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14811,unknown,ONLINE PLATFORM OF PRICES AND VOLUMES OF FRUITS AND VEGETABLES IN THE CONCENTRATING MARKETS OF THE METROPOLITAN AREA OF BUENOS AIRES,,2020,-99,INTA - ESTACIÓN EXPERIMENTAL AGROPECUARIA ÁREA METROPOLITANA DE BUENOS AIRES,7200,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C14812,unknown,SMART CITIES: DEVELOPMENT OF AN INTEGRATED TERRITORIAL INFORMATION SYSTEM FOR POST-PANDEMIC RESILIENT MANAGEMENT.,,2020,-99,UNIVERSIDAD NACIONAL ARTURO JAURETCHE,10929.6,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Data Management and Data Sharing,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14813,unknown,"SOCIO-ENVIRONMENTAL STRATEGIES FOR THE STRENGTHENING OF THE COMMUNITY, IN THE FACE OF GLOBAL AND LOCAL PANDEMIC PROBLEMS, IN THE RECONQUISTA AREA, BUENOS AIRES, ARGENTINA.",,2020,-99,UNIVERSIDAD NACIONAL DE SAN MARTÇ?N - INSTITUTO DE ALTOS ESTUDIOS SOCIALES,13501.15,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14814,unknown,"DEVELOPMENT OF AN ECOLOGICAL, ECONOMIC AND PREVENTIVE HEATING DEVICE (CEEP) FOR THE RESOLUTION OF HEALTH PROBLEMS DERIVED FROM CONDITIONS OF SOCIO-HABITATIONAL VULNERABILITY IN THE CITY OF TANDIL IN THE CURRENT CONTEXT OF THE COVID-19 PANDEMIC",,2020,-99,UNIVERSIDAD NACIONAL DEL CENTRO DE LA PROVINCIA DE BUENOS AIRES,4914.72,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14815,unknown,KNOW TO ACT. INSTITUTIONAL ARTICULATION PROPOSALS AIMED AT VULNERATED SECTORS OF / IN A MIDDLE RANGE CITY OF THE BONAERENSES CENTER IN THE FRAMEWORK OF THE IMPACT OF COVID 19.,,2020,-99,UNIVERSIDAD NACIONAL DEL CENTRO DE LA PROVINCIA DE BUENOS AIRES,4694.4,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14816,unknown,TERRITORIAL IMPACT OF LOCAL ARTICULATION POLICIES IMPLEMENTED IN THE CONTEXT OF COVID19 IN POPULAR NEIGHBORHOODS OF THE PARTY OF GENERAL PUEYRREDON: CAPACITY TO RESPONSE TO EMERGING NEEDS AND PROPOSALS FOR THEIR STRENGTHENING.,,2020,-99,UNIVERSIDAD NACIONAL DE MAR DEL PLATA,10656,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14817,unknown,SOCIAL AND CULTURAL IMPACT OF THE COVID-19 PANDEMIC IN ARGENTINA,,2020,-99,UNIVERSIDAD NACIONAL DEL NOROESTE DE LA PROVINCIA DE BUENOS AIRES,7200,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14818,unknown,"NUTRITIONAL OBSERVATORY OF PREGNANT WOMEN AND CHILDREN UNDER 5 YEARS OLD WITH SOCIAL VULNERABILITY AND FOOD INSECURITY, IN THE CONTEXT OF COVID-19 PANDEMIC.",,2020,-99,UNIVERSIDAD NACIONAL DE MAR DEL PLATA - ESCUELA SUPERIOR DE MEDICINA (ESM),5760,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts, +C14819,unknown,LONGITUDINAL STUDY FOR THE EVALUATION OF THE EMOTIONAL IMPACT OF ISOLATION BY COVID 19,,2020,-99,UNIVERSIDAD NACIONAL DE MAR DEL PLATA,4176,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14820,unknown,DEVELOPMENT OF A TELEMEDICINE SYSTEM FOR REMOTE MONITORING AND CONTROL OF GLUCEMIA IN HOSPITALIZED AND / OR ISOLATED PATIENTS.,,2020,-99,UNIVERSIDAD NACIONAL DE LA PLATA - CONICET - CICPBA INSTITUTO LEICI,12240.58,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,Digital Health,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C14821,unknown,EPIDEMIOLOGICAL PREVENTION AND CONTROL INTERVENTIONS IN THE POPULATION OF THE SOUTHEAST REGION OF GREAT BUENOS AIRES AFFECTED BY THE COVID-19 PANDEMIC. IMPLEMENTATION OF DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR THE NETWORK OF HOSPITALS AND HEALTH CENTERS IN THE REGION,,2020,-99,"HOSPITAL EL CRUCE ""NÉSTOR KIRCHNER"" (HEC)",14400,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Infection prevention and control | Therapeutics research, development and implementation","Diagnostics | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities", +C14822,unknown,PREVENTION OF THE SCOPE OF SARS-COVID2 AMONG WORKERS AND HEALTH WORKERS BASED ON STRENGTHENING THEIR SAFE WORK PRACTICES.,,2020,-99,UNIVERSIDAD NACIONAL DE AVELLANEDA,12254.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14823,unknown,COVID-19. SEROLOGICAL SURVEY STRATIFIED BY AGE BASED ON THE POPULATION OF THE PARTY OF TANDIL (PROVINCE OF BUENOS AIRES). MODELS FOR THE ANALYSIS OF FUTURE SCENARIOS,,2020,-99,UNIVERSIDAD DEL CENTRO DE LA PROVINCIA DE BUENOS AIRES - CONICET - CIC - FCV - CIVETAN,14400,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14824,unknown,SARS-COV-2 EPIDEMIOLOGY BASED ON CLOACAL LIQUID RESIDUES,,2020,-99,CONICET,14400,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C14825,unknown,COMMUNITY TRANSMISSION AND EPIDEMIOLOGY OF INFECTION BY SARS-COV-2 IN THE NORTHWEST OF BUENOS AIRES: SCOPE OF SEROLOGICAL TESTS.,,2020,-99,UNIVERSIDAD NACIONAL DEL NOROESTE DE LA PROVINCIA DE BUENOS AIRES,14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14826,unknown,SURVEILLANCE OF THE CIRCULATION OF SARS-COV-2 IN URBAN AREAS THROUGH VIRAL MONITORING OF WASTEWATER.,,2020,-99,CONICET - CCT MAR DEL PLATA - INSTITUTO DE INVESTIGACIONES EN BIODIVERSIDAD Y BIOTECNOLOGÇ?A (INBIOTEC),14400,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14827,unknown,"UNIVERSITY AND MUNICIPALITIES: STATISTICAL MODELING OF SCENARIOS AND PROMO-PREVENTIVE ACTIONS IN THE TERRITORY FOR LOCALITIES WITH LESS THAN 500,000 INHABITANTS OR LOW NUMBER OF CASES",,2020,-99,UNIVERSIDAD NACIONAL DE MAR DEL PLATA - ESCUELA SUPERIOR DE MEDICINA,13104,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Impact/ effectiveness of control measures, +C14828,unknown,"INTELLIGENT MONITORING FOR THE EARLY DETECTION OF SARS- COV-2: EPIDEMIOLOGY, MODELING AND IMPACT OF HEALTH AND SCIENTIFIC POLICIES.",,2020,-99,LABORATORIO MUNICIPAL DE VIROLOGÇ?A MOLECULAR. HOSPITAL ?BLAS L. DUBARRY?,14400,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease surveillance & mapping | Policy research and interventions, +C14829,unknown,DETECTION OF SARS- COV-2 IN ENVIRONMENTAL SAMPLES OF PARTICULATE MATERIAL AND WASTEWATER,,2020,-99,UNIVERSIDAD NACIONAL DE QUILMES,14400,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen, +C14830,unknown,ARGENTUM MEDERIS PROGRAM PART II: ROBOT TITLE MOBILE ULTRASOUND SANITIZER FOR OPEN SPACES.,,2020,-99,UNIVERSIDAD NACIONAL DE LOMAS DE ZAMORA - FAC DE INGENIERÇ?A.,14356.8,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14831,unknown,BIOCIDAL COATING FOR PROTECTIVE ELEMENTS FOR SANITARY PERSONNEL,,2020,-99,"UNIVERSIDAD TECNOLÇÿGICA NACIONAL, REGIONAL LA PLATA",14400,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14832,unknown,ASSESSMENT OF VIRICIDAL CAPACITY OF SPRAY DISINFECTION CHAMBERS,,2020,-99,UNIVERSIDAD NACIONAL DEL CENTRO DE LA PROVINCIA DE BUENOS AIRES,1440,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14833,unknown,TREATMENT OF PNEUMONIA ASSOCIATED WITH MECHANICAL VENTILATION: COFACTOR OF MORTALITY IN COVID-19 POSITIVE PATIENTS.,,2020,-99,CONICET- CCT LA PLATA - INIFTA,10080,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management", +C14834,unknown,VARIABLE FLOW VENTURI VALVE FOR USE IN OXYGEN MASKS- COVID-19 TREATMENT,,2020,-99,UNIVERSIDAD NACIONAL DE TRES DE FEBRERO,10869.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C14835,unknown,DEVELOPMENT AND STANDARDIZATION OF A QUANTITATIVE TEST FOR THE DETERMINATION OF THE VIRAL LOAD OF SARS-COV-2 IN PATIENTS WITH COVID19,,2020,-99,UNIVERSIDAD NACIONAL DE LA PLATA - FACULTAD DE CIENCIAS MÉDICAS,14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14836,unknown,IMPLEMENTATION OF AN EPIDEMIOLOGICAL SURVEILLANCE STRATEGY FOCUSED ON GROUPS WITH HIGH RISK OF INFECTION BY SARS-COV-2 IN THE HEALTH REGION 1,,2020,-99,UNIVERSIDAD NACIONAL DEL SUR,14400,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C14837,unknown,"STRENGTHENING THE DIAGNOSTIC AND RESEARCH CAPABILITIES OF THE PUBLIC HEALTH LABORATORY OF THE FACULTY OF EXACT SCIENCES (UNLP), INTEGRATED TO THE SARS-COV-2 DIAGNOSTIC NETWORK OF THE PROVINCE OF BUENOS AIRES",,2020,-99,UNIVERSIDAD NACIONAL DE LA PLATA,13993.92,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14838,unknown,CARRAGENAN NASAL SPRAY TO AVOID NEUROGENIC RESPIRATORY STRESS FROM COVID-19.,,2020,-99,UNIVERSIDAD DE BUENOS AIRES - CONICET - INSTITUTO DE FISIOLOGÇ?A BIOLOGÇ?A MOLECULAR Y NEUROCIENCIAS,7200,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C14839,unknown,IMPLEMENTATION OF A PLATFORM FOR THE ANALYSIS OF THE NEUTRALIZING ACTIVITY OF ANTI-SARS-COV-2 ANTIBODIES IN THE PLASMA OF CONVOLVING PATIENTS TO BE USED AS A TREATMENT.,,2020,-99,CONICET - INBIRS,12384,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management", +C14840,unknown,"DESIGN OF PROTOTYPES FOR THE DISINFECTION OF REDUCED PUBLIC ENVIRONMENTS, OF HIGH VIRAL DENSITY, APPLYING UV RADIATION",,2020,-99,UNIVERSIDAD NACIONAL DE CATAMARCA - FACULTAD DE TECNOLOGÇ?A Y CIENCIAS APLICADAS,13968,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14841,unknown,"PANDEMIC, ECONOMY AND POLICY RESPONSES BETWEEN LEVELS OF GOVERNMENT OF THE PROVINCE OF CHACO",,2020,-99,UNIVERSIDAD NACIONAL DEL NORDESTE,12960,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts, +C14842,unknown,"INCIDENTS OF TERRITORIAL, URBAN AND HOUSING CONDITIONS IN",,2020,-99,UNIVERSIDAD NACIONAL DEL NORDESTE,14385.6,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14843,unknown,THE CONTAINMENT AND SPREAD OF COVID-19 IN THE PROVINCE OF CHACO. PUBLIC POLICY RECOMMENDATIONS.,,2020,-99,N/A,,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,,Americas,,,,,Argentina,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C14844,unknown,"COVID-19 IN CHUBUT: MENTAL HEALTH IN ESSENTIAL SERVICES WORKERS AND THE POPULATION IN A SITUATION OF PSYCHOSOCIAL VULNERABILITY. EVALUATION OF THE SITUATION AND INTERVENTIONS IN NETWORKS AND CARE DEVICES """,,2020,-99,UNIVERSIDAD NACIONAL DE LA PATAGONIA SAN JUAN BOSCO,11059.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14845,unknown,"INTELLIGENT PROSPECTIVE ANALYSIS OF THE SOCIAL, ECONOMIC AND PRODUCTIVE IMPACT OF COVID-19 IN THE PROVINCE OF CHUBUT",,2020,-99,CCT - CONICET - CENPAT,14256,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C14846,unknown,PROTECTION OF MEDICAL PERSONNEL IN THE CARE OF THE COVID-19 PANDEMIC. SYSTEMS OF EXTRACTION AND TREATMENT OF AIR EXHALED BY INFECTED PATIENTS.,,2020,-99,CONICET - CCT CENPAT - CESIMAR,14400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14847,unknown,SOLIDARITY MAPPING: DEMANDS AND COMMITMENTS IN THE FACE OF THE COVID-19 CRISIS,,2020,-99,Universidad Nacional de Córdoba,4939.2,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",, +C14848,unknown,"THE GRAN RÍO CUARTO (GRC) IN THE SOCIAL-HEALTH EMERGENCY. LOCAL IMPACTS OF SOCIAL, PREVENTIVE AND COMPULSORY ISOLATION (ASPO)",,2020,-99,UNIVERSIDAD NACIONAL DE RÇ?O CUARTO- Y CENTRO DE OPERACIONES DE EMERGENCIA (COE) REGIONAL RÇ?O CUARTO,3600,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14849,unknown,"ENVIRONMENTAL MONITORING OF SARS-COV-2 IN SEWAGE WATERS OF THE CITY OF CÓRDOBA, ARGENTINA",,2020,-99,Universidad Nacional de Córdoba,9432,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen, +C14850,unknown,OPTIMIZATION OF THE INTEGRAL SANITARY FURNITURE (MASI) FOR PERSONAL AND FAMILY HYGIENE.,,2020,-99,CONICET - CCT CÇÿRDOBA,4608,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14851,unknown,MONITORING AND TERRITORIAL DYNAMICS OF THE PANDEMIC (COVID19) IN THE PROVINCE OF CÓRDOBA. INFORMATION FOR DECISION MAKING.,,2020,-99,Universidad Nacional de Córdoba,4104,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14852,unknown,MONITORING AND PREDICTION SYSTEM OF COVID-19 IN THE PROVINCE OF CORRIENTES USING DATA ASSIMILATION,,2020,-99,UNIVERSIDAD NACIONAL DEL NORDESTE,13809.6,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14853,unknown,DEVELOPMENT OF EVALUATION SYSTEMS ON N95 PERSONAL PROTECTION RESPIRATORS AND ITS APPLICATION TO LOCAL POTENTIALLY APPLICABLE UV-C EMERGENCY DECONTAMINATION SYSTEMS,,2020,-99,UNIVERSIDAD DE BUENOS AIRES,7344,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14854,unknown,"WASTE MANAGEMENT IN TIMES OF HEALTH EMERGENCY: REPRESENTATION OF A VULNERABILITY INDEX LINKED TO COVID- 19 IN A GIS ENVIRONMENT """,,2020,-99,UNIVERSIDAD NACIONAL DE ENTRE RÇ?OS- FACULTAD DE CIENCIAS DE LA SALUD,4392,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14855,unknown,PRODUCTION OF EPIDEMIOLOGICAL INFORMATION ON MENTAL HEALTH AND STRENGTHENING COMMUNITY INITIATIVES FOR REMOTE INTERVENTION IN MENTAL HEALTH IN THE FACE OF ASPO COVID-19 IN THE PROVINCE OF ENTRE RÍOS,,2020,-99,"UNIVERSIDAD AUTÇÿNOMA DE ENTRE RÇ?OS - FACULTAD DE HUMANIDADES, ARTES Y CIENCIAS SOCIALES",7735.68,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14856,unknown,STUDY OF THE SEROPREVALENCE OF SARS-COV2 IN THE PROVINCE OF JUJUY,,2020,-99,"UNIVERSIDAD NACIONAL DE JUJUY. INSTITUTO DE ESTUDIOS CELULARES, GENÉTICOS Y MOLECULARES (ICEGEM)",14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14857,unknown,NORTHEAST SANITARY CORRIDOR OF LA PAMPA: ADAPTATION OF MOBILE POSTS FOR PRIMARY HEALTH CARE IN RURAL AREAS OF THE MUNICIPALITY OF QUEMÚ QUEMÚ,,2020,-99,UNIVERSIDAD NACIONAL DE LA PAMPA,14212.8,Unspecified,Unspecified,Unspecified,Rural Population/Setting,Not applicable,Not applicable,Unspecified,Not applicable,Unspecified,,,,,,,,,Unspecified,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience | Health Systems Research",Communication | Health service delivery, +C14858,unknown,"STRENGTHENING THE FOOD CONTAINMENT NETWORK OF FAMILY FARMING OF THE DEPARTMENT OF CHILECITO, IN THE FRAMEWORK OF THE COVID19 PANDEMIC",,2020,-99,UNIVERSIDAD NACIONAL DE CHILECITO,6703.2,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14859,unknown,"OPTIMIZATION OF THE PROTOCOL FOR COVID-19 DIAGNOSIS BY MOLECULAR BIOLOGY, STATISTICAL ANALYSIS OF ITS MUTATION RATE AND IDENTIFICATION OF PROVINCIAL LINEAGES",,2020,-99,"INSTITUTO REGIONAL DE PLANIFICACIÇÿN, CONTROL Y SERVICIOS AMBIENTALES - IREPCYSA",14328,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations", +C14860,unknown,DESIGN OF METHODOLOGY AND IMPLEMENTATION OF TRACEABILITY SYSTEM AND PROTOCOLS IN THE FRAMEWORK OF COVID-19 FOR VEGETABLE BAGS DISTRIBUTED IN MENDOZA BY FAMILY FARM PRODUCERS,,2020,-99,INTA,8553.6,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14861,unknown,"USE OF INTELLIGENT MAPS FOR THE STUDY OF THE SPREAD OF COVID-19 IN THE MUNICIPALITY OF GUAYMALLÉN, MENDOZA",,2020,-99,CONICET - CCT MENDOZA,12736.8,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14862,unknown,PRESENCE AND MONITORING OF SARS-COV-2 IN WASTEWATER IN THE PROVINCE OF MENDOZA,,2020,-99,CONICET,14400,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen, +C14863,unknown,"SOCIAL, PREVENTIVE AND COMPULSORY ISOLATION FOR POPULAR SECTORS IN A SITUATION OF OVERCROWDING AND HOUSING PRECARITY.",,2020,-99,"CONICET- CCT MZA - INSTITUTO DE AMBIENTE, HÁBITAT Y ENERGÍA. INAHE",14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14864,unknown,USE OF CONVALECIENTS PLASMA FOR THE TREATMENT OF PATIENTS WITH COVID-19,,2020,-99,CONICET,14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trial (unspecified trial phase)", +C14865,unknown,EXPANSION OF THE DIAGNOSTIC CAPACITY OF SARS-COV2 IN THE PROVINCE OF MISIONES,,2020,-99,UNIVERSIDAD NACIONAL DE MISIONES - CONICET - INSTITUTO DE BIOLOGÇ?A SUBTROPICAL,14400,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,,, +C14866,unknown,SENSES AND POSSIBILITIES OF NEUQUINE EDUCATION IN TIMES OF PANDEMIC,,2020,-99,CONICET - UNIVERSIDAD NACIONAL DEL COMAHUE - IPEHCS. INSTITUTO PATAGÇÿNICO DE ESTUDIOS DE HUMANIDADES Y CIENCIAS SOCIALES,9792,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14867,unknown,STRATEGIC COMMUNICATION FOR HEALTH AND COMMUNITY CARE IN LOCATIONS WITH A HIGH RATE OF COVID-19 CONTAGATION,,2020,-99,UNIVERSIDAD NACIONAL DEL COMAHUE - FACULTAD DE DERECHO Y CIENCIAS SOCIALES,4435.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Policies for public health, disease control & community resilience",Communication, +C14868,unknown,INEQUALITIES AND SOCIO-ECONOMIC IMPACTS OF COVID-19 IN THE PROVINCE OF NEUQUÉN.,,2020,-99,UNIVERSIDAD NACIONAL DEL COMAHUE - CONICET - INSTITUTO PATAGÇÿNICO DE ESTUDIOS EN HUMANIDADES Y CIENCIAS SOCIALES (IPEHCS),6480,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14869,unknown,OF PANDEMICS AND FOOD SAFETY: MAPPING OF SHORT SUPPLY CIRCUITS IN RÍO NEGRO,,2020,-99,UNIVERSIDAD NACIONAL DE RÇ?O NEGRO,5760,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14870,unknown,"DESIGN, MANUFACTURE AND TESTING OF A DISINFECTION SYSTEM BASED ON UV-C RADIATION, PORTABLE AND LOW COST FOR PUBLIC TRANSPORTATION",,2020,-99,CONICET - CCT PATAGONIA NORTE,6969.6,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14871,unknown,PRODUCTION OF ETHYL ALCOHOL IN NORTHERN PATAGONIA FOR USE IN THE PREPARATION AND LOCAL SUPPLY OF SANITIZANT,,2020,-99,CONICET - CCT PATAGONIA NORTE,5040,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14872,unknown,DEVELOPMENT AND PRODUCTION OF SANITIZERS AND DISINFECTANTS FOR HOSPITALS IN THE IV SANITARY ZONE OF RÍO NEGRO,,2020,-99,CNEA - CONICET - DEPARTAMENTO CARACTERIZACIÇÿN DE MATERIALES - GERENCIA DE INVESTIGACIÇÿN APLICADA - INN COMISIÇÿN NACIONAL DE ENERGÇ?A ATÇÿMICA,14400,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14873,unknown,STRENGTHENING A PILOT LABORATORY OF REHABILITATION AND PHYSIOTHERAPY FOR PATIENTS IN RECOVERY OF COVID 19 AND RELATED PATHOLOGIES,,2020,-99,UNIVERSIDAD NACIONAL DE RIO NEGRO,14356.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences", +C14874,unknown,DETERMINATION OF THE AERIAL VIRAL LOAD OF SARS-COV-2 IN HOSPITALS AND SPACES ENABLED FOR THE TREATMENT OF PATIENTS WITH COVID-19 IN SALTA,,2020,-99,UNIVERSIDAD NACIONAL DE SALTA - CONICET - INSTITUTO DE INVESTIGACIONES PARA LA INDUSTRIA QUÇ?MICA (INIQUI),13680,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen, +C14875,unknown,IMPLEMENTATION OF A NETWORK SUPPORT AND CONTROL SYSTEM FOR 30 HEALTH CENTERS AND 14 HOSPITALS DEPENDENT ON A REFERENCE HOSPITAL FOR COVID19 PATIENTS.,,2020,-99,HOSPITAL PAPA FRANCISCO. CENTRO DE CONTINGENCIA COVID 19,10512,Other,Not applicable,Not Applicable,Not applicable,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery", +C14876,unknown,RISK ASSESSMENT OF SARS-COV-2 THROUGH PERSISTENCE AND VIABILITY TESTS ON DIFFERENT SURFACES APPLYING A VIRAL MODEL.,,2020,-99,UNIVERSIDAD NACIONAL DE SALTA - CONICET - INIQUI ? LABORATORIO DE AGUAS Y SUELO,12697.92,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen, +C14877,unknown,DEVELOPMENT AND PERFORMANCE EVALUATION OF A RESPIRATORY PROTECTION MASK SUITABLE FOR SELF-CONFECTION,,2020,-99,UNIVERSIDAD NACIONAL DE SALTA,14342.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14878,unknown,NEW RT-QPCR MULTIPLEX SYSTEM FOR THE MOST SENSITIVE AND ECONOMIC DIAGNOSIS OF SARS-COV-2 / H1N1,,2020,-99,UNIVERSIDAD NACIONAL DE SALTA - CONICET - INSTITUTO DE INVESTIGACIONES PARA LA INDUSTRIA QUÇ?MICA (INIQUI),14400,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14879,unknown,CONSTRUCTION OF A WEB GIS AS A TOOL FOR THE DESIGN OF CONTINGENCY PLANS IN THE CONTEXT OF SOCIAL-HEALTH EMERGENCY (COVID-19).,,2020,-99,UNIVERSIDAD NACIONAL DE LA PATAGONIA AUSTRAL - UNIDAD ACADÉMICA CALETA OLIVIA,11692.8,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C14880,unknown,"STRENGTHENING LOCAL AND PROVINCIAL CAPACITIES TO SUPPORT WORKERS FROM THE SOCIAL, SOLIDARITY, POPULAR AND FAMILY FARMING ECONOMY IN THE CONTEXT CAUSED BY THE COVID-19 PANDEMIC.",,2020,-99,UNIVERSIDAD NACIONAL DE ROSARIO,3528,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Economic impacts, +C14881,unknown,STRENGTHENING LOCAL EPIDEMIOLOGICAL MONITORING OF COVID-19 IN ASYMPTOMATIC PEOPLE TO IMPROVE THE HEALTH NETWORK OF THEIR APPROACH,,2020,-99,UNIVERSIDAD NACIONAL DEL LITORAL,14400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C14882,unknown,COVID 19 GEOPORTAL FOR THE PROVINCE OF SANTA FE,,2020,-99,UNIVERSIDAD NACIONAL DEL LITORAL,3600,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,,, +C14883,unknown,LARGE SCALE TESTING PLATFORM FOR THE DETECTION OF SARS-COV-2 BASED ON DROPLET DIGITAL PCR.,,2020,-99,UNIVERSIDAD NACIONAL DEL NORDESTE - FACULTAD DE MEDICINA,14400,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14885,unknown,EXPANSION OF THE DIAGNOSTIC CAPACITY OF COVID-19 IN THE PROVINCE OF SANTA FE THROUGH THE SCIENTIFIC-TECHNOLOGICAL STRENGTHENING OF THE CTSP LABORATORY UNDER THE NATIONAL UNIVERSITY OF ROSARIO.,,2020,-99,UNIVERSIDAD NACIONAL DE ROSARIO. FACULTAD DE CIENCIAS BIOQUÍMICAS Y FARMACÉUTICAS.,12960,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C14886,unknown,MULTIPLEX SEQUENCING OF SARS-COV-2 IN CLINICAL SAMPLES,,2020,-99,UNIVERSIDAD NACIONAL DE ROSARIO,11520,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C14887,unknown,ANALYSIS OF COMPLETE GENOMES OF THE SARS-COV-2 VIRUS CIRCULATING IN THE PROVINCE OF SANTA FE IN 2020,,2020,-99,INTA - EEA RAFAELA,14398.85,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C14888,unknown,DEVELOPMENT OF MULTIVARIATE ANALYTICAL METHODS (NIR / PLS) FOR THE DETERMINATION OF ACTIVE PRINCIPLES IN RAW MATERIAL AND SEMI-PREPARED PRODUCTS OF MEDICINAL SPECIALTIES LINKED TO COVID-19 FROM THE LABORATORY OF PUBLIC PRODUCTION OF MEDICINES,,2020,-99,UNIVERSIDAD NACIONAL DEL LITORAL,13793.76,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies, +C14889,unknown,IDENTIFICATION OF SIGNIFICANT INSTITUTIONAL AND COMMUNITY STRATEGIES AND DEVICES TO MITIGATE THE SOCIAL EFFECTS OF MANDATORY PREVENTIVE SOCIAL ISOLATION IN TERRITORIES,,2020,-99,UNIVERSIDAD NACIONAL DE SANTIAGO DEL ESTERO,7200,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14890,unknown,"OZONE GENERATION, CONTACT AND CONTROLLED DEACTIVATION TECHNOLOGICAL PLATFORMS FOR SANITIZATION OF ENVIRONMENTS, SURFACES AND TEXTILES.",,2020,-99,UNIVERSIDAD NACIONAL DE SANTIAGO DEL ESTERO,14400,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14891,unknown,PREVENTION AGAINST COVID-19 THROUGH STRENGTHENING FOOD SOVEREIGNTY IN THE SAN JUAN MOUNTAIN AREAS,,2020,-99,INTA - ESTACIÇÿN EXPERIMENTAL AGROPECUARIA (EEA) SAN JUAN,4435.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14892,unknown,COVID-19 INFORMATION SYSTEM OF THE PROVINCE OF SAN JUAN DE LA GEOREFERENCED HEALTH INFRASTRUCTURE AND ESSENTIAL INFORMATION SERVICES FOR POSSIBLE CASES AT THE LEVEL OF GRAN SAN JUAN AND REMOTE MUNICIPALITIES.,,2020,-99,"UNIVERSIDAD NACIONAL DE SAN JUAN - FACULTAD DE ARQUITECTURA, URBANISMO Y DISEÑO",12240,Other,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C14893,unknown,GEOGRAPHICAL INFORMATION SYSTEM FOR THE TERRITORIAL RECEPTION CAPACITY OF SAN JUAN FOR THE MITIGATION OF THE IMPACT OF COVID-19.,,2020,-99,UNIVERSIDAD NACIONAL DE SAN JUAN,3916.8,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Impact/ effectiveness of control measures, +C14894,unknown,MODULAR SYSTEM OF ACOUSTIC SEPARATORS TO GENERATE ADAPTABILITY OF USE TO PRE-EXISTING SPACES- COVID19.,,2020,-99,UNIVERSIDAD NACIONAL DE SAN JUAN,8909.28,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14895,unknown,PSYCHOTHERAPY IN TIMES OF QUARANTINE DURING THE COVID-19 PANDEMIC. PERSPECTIVE OF MENTAL HEALTH PROFESSIONALS,,2020,-99,UNIVERSIDAD NACIONAL DE SAN LUIS,4092.48,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14896,unknown,"RESEARCH AND STRENGTHENING THE SKILLS OF HEALTHCARE PERSONNEL FOR THE PREVENTION OF TRANSMISSION TO THE WORKER, ACTION IN THE EMERGENCY AND MANAGEMENT OF PATIENTS WITH COVID-19.",,2020,-99,UNIVERSIDAD NACIONAL DE VILLA MERCEDES,5039.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,IPC in health care settings, +C14897,unknown,"RESEARCH AND DEVELOPMENT OF DISINFECTANT PRODUCTS AND SYSTEMS FOR USE IN PEOPLE, MEDICAL DEVICES AND SURFACES IN HEALTH CARE ENVIRONMENTS.",,2020,-99,UNIVERSIDAD NACIONAL DE VILLA MERCEDES,11088,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14899,unknown,TIMES OF PANDEMIC: THE INITIAL LITERACY IN A SITUATION OF SOCIAL VULNERABILITY,,2020,-99,CONICET - CCT TUCUMAN - UNIVERSIDAD NACIONAL DE TUCUMÁN - INSTITUTO DE INVESTIGACIONES SOBRE EL LENGUAJE Y LA CULTURA (INVELEC),7446.24,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Social impacts, +C14900,unknown,"ASSESSMENT OF THE JOINT INCIDENCE OF COVID, ILI AND PNEUMONIA ON THE HEALTH SYSTEM OF THE PROVINCE OF TUCUMÁN.",,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN,9648,Unspecified,Not applicable,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C14901,unknown,COVID-U-MAP: A PLATFORM FOR THE ENVIRONMENTAL MAPPING OF SARS-COV-2 AND OTHER EMERGING PATHOGENS IN THE GREAT SAN MIGUEL DE TUCUMÁN.,,2020,-99,CONICET - CCT NOA SUR,14400,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Epidemiological studies,Disease surveillance & mapping, +C14902,unknown,NEW URBAN PROGRAM TOOLS FOR LOCAL MANAGEMENT IN COVID SCENARIOS,,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN,6480,Unspecified,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C14903,unknown,DEVELOPMENT OF PORTABLE EQUIPMENT FOR DISINFECTION OF PATHOGENS IN AIR AND ON SURFACES BY USING UV RADIATION: APPLICATION IN AMBULANCES AND PUBLIC PREMISES,,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN - FACULTAD DE CIENCIAS EXACTAS Y TECNOLOGÍA,10800,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14904,unknown,PUBLIC PRODUCTION OF ALCOHOL IN GEL INTENDED FOR PRODUCTIVE AND VULNERABLE SECTORS OF THE PROVINCE OF TUCUMÁN,,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN,14400,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C14905,unknown,DEVELOPMENT OF TWO DEVICES FOR THE DETECTION OF SYMPTOMS ASSOCIATED WITH COVID 19,,2020,-99,CONICET - CCT NOA SUR,3600,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Clinical characterisation and management,"Supportive care, processes of care and management", +C14906,unknown,COMPARATIVE STUDY OF THE GENETIC EXPRESSION OF IMMUNE CELLS OF SICK PEOPLE WITH COVID-19 AND WITH DIABETES MELLITUS TYPE 2 VERSUS SICKNESS WITHOUT COMORBIDITY. ITS PROJECTION IN THE TREATMENT AND MONITORING OF THE DISEASE.,,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN,14400,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Disease pathogenesis | Supportive care, processes of care and management", +C14907,unknown,BIOCIDAL EFFECT OF CHLORINE DIOXIDE ON COVID-19 ASSESSED BY ELECTRON MICROSCOPY,,2020,-99,UNIVERSIDAD NACIONAL DE TUCUMÁN,14400,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Ministerio de Ciencia, Tecnología e Innovación [Ministry of Science, Technology and Innovation] (MINCYT)",Argentina,Americas,Americas,Americas,,,,Argentina,Argentina,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C15047,2007929,Harnessing immunity for optimal SARS-CoV-2 and influenza vaccines,"Vaccines are our most important public health measure to combat infection, however the optimal vaccine format and dosing, or duration of immunity towards influenza virus and SARS-CoV-2 is poorly understood. We need to pre-arm our immune system against antigenic drift and future outbreak strains. This proposal will determine the protective potential of broadly-reactive immune responses by current vaccines, recovered patients, and experimental vaccines for influenza viruses and SARS-CoV-2.",2021,-99,University of Melbourne,1149327.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity, +C15048,2009278,Mathematical modelling to support policy decisions on COVID-19 vaccination in Australia,"Vaccination against COVID-19 is underway globally. However, even as the virus is controlled by vaccination, it will be very difficult to eliminate COVID-19 completely, and we will need additional vaccine doses to boost protection against current and variant strains. I will use mathematical models to estimate the health benefit of COVID-19 vaccines, and to inform policy planning for longer-term, sustainable COVID-19 vaccine programs in Australia and regionally.",2021,-99,UNSW Sydney,476341.68,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Epidemiological studies | Vaccines research, development and implementation",Impact/ effectiveness of control measures, +C15049,2009323,Restoring the Fair Go: which policies and practices are likely to reverse growing health inequities in Australia post-COVID-19,"Australia has become a less equal society. My 'Restoring the Fair Go' program will analyse the underlying economic and health inequity trends, assess the policies that have contributed to these inequalities and determine how these can be reversed. The program will explore Australian policymaker and citizens perspectives on inequality and draw comparisons to other OECD countries. Practical policy proposals will be developed to help Australia build back from COVID-19.",2021,-99,Flinders University,1644062.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Economic impacts | Health service delivery, +C15050,2010051,Mitigating the impacts of infectious disease emergencies,"While public health and social measures have been central to the COVID-19 response and saved lives, many uncertainties remain as to their optimal use. Governments have been repeatedly required to balance the consequences of an uncontrolled outbreak against the social and economic costs of interventions. Over the next five years, I will use modelling and decision science to support the development of more tailored and adaptive response policies for COVID-19 and inevitable future pandemics.",2021,-99,University of Melbourne,476341.68,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C15051,2010091,Research generating evidence to optimise pneumococcal disease prevention,This research program aims to develop an in-depth understanding of various streptococcus pneumoniae (SP) infections that could be serious and even life threatening. Antibiotic resistance and how COVID-19 and influenza could make people vulnerable to SP infections will be two key areas explored. This research is expected to feed directly in to practice and policy relating to pneumococcal disease surveillance and optimizing prevention using vaccinations during COVID-19 pandemic and beyond.,2021,-99,University of Sydney,329670.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Pandemic-prone influenza,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,Clinical characterisation and management,Disease pathogenesis, +C15052,2010212,Behavioural and social science to close gaps in vaccination coverage,"COVID-19 has cost trillions in economic loss globally and devastated entire nations. The pandemic now has the capacity to be much better controlled with vaccination. But the best vaccines - those against COVID-19 and other diseases - are of no use if the public will not, or cannot, take them. This research will help countries to gather a better understanding of why people don't vaccinate and what to do about it.",2021,-99,University of Sydney,1736721.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy, +C15053,2010757,COVID-19-induced vascular complications: mechanisms and potential therapies,"The coronavirus SARS-CoV-2 is responsible for the disease COVID-19, which causes significant lung dysfunction. Importantly, reports have observed COVID-19 symptoms that are not associated with the lungs, such as blood clots, vessel inflammation and leakage of fluid from vessels into tissues. These virus-induced vessel defects can lead to the death of patients. Here, we aim to understand exactly how these vessel defects occur to develop treatments for patients with acute and long term disease.",2021,-99,University of Queensland,531379.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C15054,2010917,Targeting neuropilin in SARS-Cov-2 neuronal uptake and transport,"COVID-19 is associated with a variety of neurological symptoms, ranging from a transient loss of smell and taste to headaches to severe ischaemic damage in fatal cases. The long-term consequences of potential interactions of the causative virus, SARS-CoV-2, with brain cells are currently unknown but could be linked to intractable neuronal degeneration as previously found with the 1918 influenza pandemic. We will investigate the uptake and transport of the virus and find ways to block infection.",2021,-99,University of Queensland,669911.37,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis", +C15055,2011044,COMBAT - A Combination B-and T-Cell Epitope Vaccine to Futureproof COVID-19 Vaccine,"We are proposing a vaccine that contains only safe components of the SARS-CoV-2 virus, yet effectively elicits protective immunity. The vaccine works by inducing antibodies capable of preventing the virus from attaching to lung cells, and killer T cells that destroy virus-infected cells. This highly innovative approach will generate a much needed safe and prophylactic 2nd generation modular vaccine, ideal for ""vaccine update"" that will have a major impact on health and society more generally.",2021,-99,Griffith University,897133.25,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Australia,Australia,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase), +C15056,2011398,Development of a defective interfering RNA based antiviral approach to treat infections by SARS-CoV-2 and emerging variants,"Specific therapy for severe disease caused by SARS-CoV-2 is limited. The ability of viruses to become resistant to a therapy may be obstacle for antiviral development. This project develops a unique platform, using virus-specific antiviral RNA, as a unique and possibly ""antiviral-resistance"" proof approach that could be deployed as a therapeutic for COVID-19 and also help to solve the challenge of viral pandemics from known and unknown viruses, especially other human pathogenic coronaviruses.",2021,-99,QIMR Berghofer Medical Research Institute,603914.24,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies, +C15057,2011467,Defining the impact of chronic lung disease on COVID-19 and developing effective therapies,"COVID-19 disease is driven by virus-induced, hyper-inflammation that damages the lungs. Patients with chronic lung disease, such as chronic obstructive pulmonary disease (COPD) and tuberculosis (TB), have increased severity of COVID-19 disease. Using our models of TB and smoking-induced COPD, we will define how chronic lung disease increases the severity of COVID-19, how CoV2 infection exacerbates TB and COPD, and identify effective drugs that suppress this inflammatory damage to the lung.",2021,-99,University of Sydney,664337.74,Human Populations | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C15058,2012074,The ADEPT study: Adaptive Diagnostics for Emerging Pandemic Threats in regional Australia,"This project will develop regional diagnostic tests for serious infections, using technical advances made against COVID-19. We will apply these rapid, simple to operate technologies in regional Western Australia. This project will involve regional indigenous communities to reduce the physical, mental and cultural harm done when people are shipped out of country to run diagnostic tests for conditions that could be treated with confidence locally when an early, specific diagnosis is available.",2021,-99,University of Western Australia,2544218.04,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C15059,2012769,Harnessing the beneficial off-target effects of BCG vaccination to boost protection against SARS-CoV-2,"Bacillus Calmette-Guérin(BCG), the vaccine that protects against tuberculosis, also protects against other diseases. This is thought to be because BCG can boost immunity. We will investigate how BCG boosts immune responses to SARS-CoV-2 and if this improves protection against COVID-19 and the effectiveness of COVID-19 vaccines. We will combine use of mouse models with use of samples from BRACE, our 6800 participant trial testing if BCG vaccination protects against COVID-19 in healthcare workers.",2021,-99,Murdoch Childrens Research Institute,804156.18,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Disease models | Prophylactic use of treatments, +C15060,2012863,"Dissecting the healthy and immunosuppressed, primary and secondary immune responses within human lymph nodes following COVID-19 vaccination",The dynamics of the immune response to vaccines in human lymph nodes are important in determining eventual vaccine responses but are poorly characterised. We will investigate the critical components of the immune response in human lymph nodes that lead to an effective neutralising antibody response to novel COVID-19 vaccines. Our findings will provide insights into the critical responses required for a successful vaccine and will inform the rational design of future vaccines.,2021,-99,UNSW Sydney,727961.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity, +C15061,2012883,Predicting and preparing for the unfolding evolution of SARS-CoV-2,"One year on from the emergence of the COVID-19 pandemic, variants of SARS-CoV-2 have evolved to be more transmissible, pathogenic and less susceptible to immune responses from infection or vaccination. We propose utilising the deep mutational scanning method to examine the molecular pathogenesis and vaccine escape of SARS-CoV-2 at a single amino acid residue resolution and towards developing a universal vaccine candidate to neutralise all potential future SARS-CoV-2 variants.",2021,-99,University of Queensland,740678.51,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies", +C15062,2013563,Evaluating Systems Change for Health Equity: A Case Study of Australia's COVID-19 Policy Response,"This project will build new resources to evaluate the impact of policy reforms on changes to the underlying societal structures that shape health inequity. Using systems science we will study Australia's COVID-19 policy response and the impact it will have on the rules, norms, power dynamics, and resource flows that stratify society and shape people's health. This new evidence will be used to advocate for policy reform that better targets the roots of health inequity in Australia and abroad.",2021,-99,Australian National University,335198.67,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C15065,GA188770-V1,Rebooting the Muse: Post-COVID-19 sustainability in the performing arts,"Rebooting the Muse advocates new ways of tackling the urgent challenges facing the Australian performing arts in the wake of the COVID-19 pandemic and climate change emergency. The research explores how new digital technologies can be deployed to offer new audience experiences, and documents the impact on artist and community wellbeing of these innovations. Project participants include prominent South Australian music and theatre organisations, and features children's theatre and Indigenous music performance groups. The research findings will drive a revision of organisational business models to better ensure sustainability across the sector, and with that, improve the wellbeing of individuals and the broader community.",2021,2024,N/A,210621.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,,Western Pacific,,,,,Australia,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C15066,GA188813-V1,Creative industries pathways to youth employment in the COVID-19,"This project aims to accredit 21st century skills developed through youth arts. The significance of this project lies in our response to the increase in Australia’s youth unemployment caused by the COVID-19 pandemic and industry demand for 21st century skills. Outcomes include pathways from arts to employment and job-ready skill development, through micro-creds that showcase skills to employers. Benefits align with UN Sustainable Development Goals 4, 5 and 8: to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all, achieve gender equality and empower all women and girls, and promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all",2021,2024,N/A,249510.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,,Western Pacific,,,,,Australia,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C15087,1P01AI165072-01,Cross-Protective Humoral Immunity to Coronavirus,"PROJECT 1 SUMMARY Global establishment of Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a continued human threat. While successful vaccine programs are well underway, genetic drift and immune escape have already begun to subvert immunity. In addition, related zoonotic coronaviruses threaten transition into the human population. CoVs can be highly transmissible and highly lethal, posing a grave threat to human lives and world economies. In this light, developing pan-CoV vaccine options in preparation for the expected broad range of SARS-CoV-2 variants and future emergent coronaviruses could save millions of lives and prevent future global catastrophes. While current SARS-CoV-2 vaccines targeting the virus spike (S) protein hold great promise in providing protection against current circulating strains, research is urgently needed to understand breadth and durability of immunity across the CoV family and to translate this information into next generation vaccines with increased breadth to cover SARS-CoV-2 escape mutants as well as to address emergent CoVs. The overall goal of this program is to produce critical information necessary for the design and testing of next generation CoV vaccine strategies with the greatest possible breadth across the CoV family. The Program team will identify humoral, cellular, and structural immunologic features influencing clinical outcomes and immune recognition breadth in human SARS-CoV-2 infection and human vaccination cohorts to fuel design and pre-clinical testing of protective coronavirus vaccine strategies to identify those with the greatest possible breadth. Project 1's goal in this process is to define B cell/serologic properties of broad CoV immunity and identify vaccine delivery conditions that can best support them. Preliminary discoveries from Project 1 together with recent literature support the working hypothesis that aspects of vaccine strategy such as antigen choice, delivery timing, dose, and valency will influence CoV recognition breadth and effectiveness. Knowledge gained from strategic analysis of the heterogeneity of active human SARS-CoV-2 convalescent and vaccine cohorts will generate new hypotheses to integrate into pre-clinical vaccine testing approach. In particular, recent work from Project 1 investigators has identified the conserved S2 domain as promising target for broad CoV immunity in humans. Program 1's roles in evaluating these hypotheses are to: 1) identify immune correlates of convalescent COVID-19 patients and vaccinees that exhibit superior durability and cross-reactivity; 2) define the mechanisms of cross-reactive monoclonal mediated protection against CoVs in vivo; and 3) evaluate the efficacy of novel vaccine immunogens to induce protective B cell/functional serological responses in animals. Supported by Core B, results from Project 1 will provide strategic antibody, serological and memory B cell analysis in the context of an integrative programmatic approach in synergy with Projects 2 and 3 approach to generate vaccine strategies with maximal breadth and effectiveness.",2021,2024,N/A,3169124,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +C15089,3R01GM124280-04S1,Modeling ongoing SARS-CoV2 vaccination strategies in light of emerging data on immunity and viral evolution,"SUMMARY While SARS-CoV-2, the pathogen causing COVID-19, continues to spread, the rapid development and deployment of effective vaccines provide a means by which we can reduce its future impact. Initial vaccines have shown to be highly effective, however, the current emergence of new SARS-CoV-2 variants, together with indications that of waning immunity, means that continued repeat vaccinations are likely to be required. Here, we will build upon resources we have already developed from our ongoing project aimed at modeling potential norovirus vaccines and our previous work aimed at modeling the impact of vaccination for SARS-CoV-2 Our team has made contributions and investigated the relative population impacts of SARS-CoV-2 vaccines with different mechanisms of action; characterized patterns of virus evolution that have the potential to impact vaccine efficacy and escape; and, examined initial strategies for vaccine deployment with the aim of relaxing social distancing guidelines. We will leverage these data and modeling tools and build on this work to assess more fully the patterns of immune waning and virus evolution. We will then use these data and results and combine them with our existing SARS-CoV-2 vaccine simulation model to inform the building and the calibration of an extended model. This extended model will account for waning immunity to SARS-CoV-2 and its viral evolution. Our model will inform rapidly emerging scientific questions around continued SARS-CoV-2 vaccination and re-vaccination strategies, including both boosting and vaccine reformulation.",2021,2023,N/A,173135,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Vaccines research, development and implementation",Disease transmission dynamics | Impact/ effectiveness of control measures | Vaccine design and administration,2018 +C15090,3U54GM104942-06S1,"Emergence, Progression and Impact of SARS-CoV-2 Variants in West Virginia","PROGRAM SUMMARY The novel coronavirus SARS-CoV-2 has swept the globe resulting in millions of deaths. Recent descriptions of variants have raised concerns regarding the impact on the effectiveness of COVID-19 therapies and preventive strategies including monoclonal antibodies and vaccines. Though COVID vaccine scale-up in West Virginia is currently among the best in the nation, West Virginia's population is highly vulnerable to emergent variants that may impact the effectiveness of current vaccines and therapeutic monoclonal antibodies. To suppress the ongoing pandemic it is critical to identify, track and isolate new variants before they spread and bring a wave of disease that is resistant to current vaccines. Noteworthy is that we have already established high throughput SARS-CoV-2 sequencing with long-standing collaborations between Marshall University, West Virginia University, and the West Virginia Department of Health and Human Resources. We are well positioned to provide rapid, impactful information regarding the prevalence, changing patterns, and clinical outcomes with respect to variants as well as on the effect of variants among those who have received a COVID-19 vaccine. This project will sequence SARS-CoV-2 from heterogeneous populations by leveraging three existing testing programs that include: 1) the Rapid Acceleration of Diagnosis in Underserved Populations (RADx-UP) that has already tested over 1,500 persons throughout the state, 2) surveillance testing among nursing home residents and staff, and 3) university surveillance testing. Through the RADx-UP initiative, testing is currently conducted in 37 counties; all positive tests will be sent for sequencing, enabling assessment of variants in disparate locations in West Virginia - some within 40 minutes of the metro Washington DC area and others in remote rural locations. Moreover, the WV RADx-UP initiative is also conducting testing among communities of color (predominantly Black/African American) enabling description of variants among this group in comparison to the general population of WV. Relevant to nursing home populations, age has been associated with lower antibody levels in both the Moderna and Pfizer Phase 3 vaccine trials. Nursing home patients may be more likely to have suboptimal immunity, a scenario that is ripe for emergence of existing or novel variants. Finally, university students by virtue of their mobility and variable adherence to social distancing measures suggest fertile ground for emergence of variants. Sequencing of all isolates from the WVU surveillance testing program will provide an excellent opportunity to assess cases caused by variants over time. As this project will support SARS-CoV-2 sequencing in multiple West Virginia populations, we are confident that this surveillance sequencing will quickly identify variant emergence and distributions so as appropriate public health measures may be implemented.",2021,2022,N/A,678030,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2012 +C15091,1R21AI163793-01,Trimerization of the N-terminal Domain of ACE2 for Bifunctional Trapping of Future SARS-CoV-2 Variants,"Abstract The Covid-19 pandemic caused by SARS-Cov-2 has resulted in 38.3 million infection cases across 188 countries and territories with more than 1.08 million deaths by October 14 2020. While various vaccines are under expedite development, there is a serious concern that future variants of SARS-COV-2 will evolve and infect humans in the near future. We propose to develop a novel class of universal molecular blockers against SARS-CoV-2 based on the N-terminal three-helix bundle (3HB, residues 20-99) of hACE2, which is recognized by both SARS-CoV and SARS-CoV-2 as cell surface receptor to infect human cells. Based on our previous work in trimerizing three-helical bundle domains, we hypothesize that the N-terminal 3HB domain of hACE2 can be trimerized for highly potent and specific binding with presumably the RBD of all variants of SARS-CoV-2. Two specific aims will be pursued in this project. In specific aim 1, we will develop a trimeric trap based on the N- terminal three-helix bundle (3HB) of hACE2 that trivalently binds to the RBD of SARS-CoV-2 with high specificity and potency. In specific aim 2, we will use directed molecular evolution to identify a human furin inhibitor from a protein domain library and fuse it with the N-terminal 3HB of hACE2 for a bifunctional SARS-CoV-2 trap that highly specifically binds viral RBD while inhibits its furin-mediated preactivation. The resulting novel SARS-CoV- 2 trapping molecules will have the potential to be universally applied to block hACE2-mediated infection by vast majority of, if not all, future variants of SARS-CoV-2.",2021,2023,N/A,224925,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity",2021 +C15092,3UM1AI148689-02S6,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site:21-0011,"Project Summary The primary goal of current COVID-19 vaccine trials is to measure vaccine efficacy (VE) against clinically significant infection. However, on a population level, vaccine efficacy against all infection, including asymptomatic or very mildly symptomatic infection, is an important endpoint. This proposal outlines an ancillary swab study to the Novavax Phase 3 SARS-CoV-2 vaccine trial (PREVENT-19) to address these knowledge gaps. With the global SARS-CoV-2 pandemic, we recognize a significant need for vaccines that not only modify COVID-19 in SARS-CoV-2 infected individuals but also reduce infection/transmission regardless of symptomatology. In this study, participants will self-swab twice weekly starting at or shortly after their second dose of either SARS-CoV-2 rS/M1 or placebo. These swabs will be tested for SARS-CoV-2 by RT-PCR. Specific Aims of this study are to estimate the efficacy of SARS-CoV-2 rS/M1 vaccine against infection, to estimate the efficacy of SARS-CoV-2 rS/M1 vaccine against asymptomatic/very mildly symptomatic infection, to determine the sequence of breakthrough SARS-CoV-2 infections, to estimate the vaccine efficacy on duration of infection, to estimate the vaccine efficacy against SARS-CoV-2 viral load as a proxy of transmission, and to explore whether observed vaccine efficacy against COVID-19 illness reflects a transition from symptomatic into asymptomatic infections versus an absolute reduction in all SARS-CoV-2 infections. This ancillary swab study will tell us much about the ability of SARS-CoV-2 rS/M1 to reduce infection regardless of symptomatology. In addition, it will provide important information on the ability of the vaccine to reduce duration of infection and transmission.",2021,2021,N/A,11669935,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2021 +C15093,1R21AI161600-01,Role of Salivary Gland Localized SARS-CoV-2 Infection in Oral Tolerance & Immunization Efficacy,"Project Summary | Role of Salivary Gland Localized SARS-CoV-2 Infection in Oral Tolerance & Immunization Efficacy Over 5 million individuals in the United States have been diagnosed with systemic acute respiratory syndrome coronavirus-2, SARS-CoV-2, infections 1. One of the primary unanswered questions is whether patients that recover from SARS-CoV-2 or are immunized against SARS-CoV-2 will develop lasting immunity. Early reports of COVID-19 have outlined the potential role of salivary gland (SG) localized SARS-CoV-2 in the development of COVID-19 symptomology. Viruses that are able to infect the salivary glands often escape complete immune-mediated clearance due to immune privilege status of the salivary glands and the development of systemic oral tolerance to oral antigens. To further analyze the role in SG localized SARS-CoV-2 infection, we will 1) develop a murine model of SARS-CoV-2 spike protein expression in salivary gland tissue to evaluate release of antigen into saliva and capacity to trigger the development of oral tolerance, 2) measure immunization-mediated clearance of SARS-CoV-2 antigens from SG tissue and 3) evaluate the impact of oral antigen exposure on existing immunization efficacy and ability to support long lasting immunity. Data obtained from the proposed studies will further define the role of SG localized SARS-CoV-2 infections and potential avenues for development of oral tolerance-based therapies.",2021,2023,N/A,228750,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease models | Disease pathogenesis,2021 +C15095,3U01AI151807-02S1,Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO),"ABSTRACT The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO) network provides a nimble and flexible network of surveillance sites in Central and South America coupled to cutting-edge modeling approaches to anticipate and counter emerging zoonoses and arboviruses. CREATE- NEO forewarns local, regional, and global public health agencies of zoonoses and arboviruses that pose particularly high risk of spillover, emergence into transmission among humans, and/or international spread. The parent grant 1U01 AI151807 supports CREATE-NEO operations during typical conditions of emerging zoonoses and arbovirus activity. Since, 2020 we have built local capacity to detect, predict and respond to such emergence events at their point of origin, thereby maximizing the potential to avert full-blown emergence. Critical activities included: (i) genomic surveillance with deep sequencing and comprehensive phylogenetic analyses of dengue virus in Sao Jose do Rio Preto (SJdRP), Brazil; (ii) vector and non-human primate surveillance in Brazil and Panama; and (iii) characterization of human cases of Zika, dengue and Ilheus virus infections associated with cerebrovascular and encephalitic events. With the onset of the COVID-19 pandemic, we expanded our activities to include: (iv) characterization of human cases of SARS-CoV-2 and dengue virus coinfection; (v) surveillance of NHPs for potential spillback of SARS-CoV-2; (vi) supporting genomic surveillance of SARS-CoV-2 variants in SJdRP and Panama; and (vii) supporting clinical surveillance of arbovirus circulation in Panama and Brazil. Thus, the emergence and rapid spread of SARs-CoV-2 offers an example of our capacity to quickly redirect resources to address any emerging zoonotic or vector-borne diseases. This U01 supplement will continue and expand these emergency activities in support of NIH-funded and other international research on SARS-CoV-2 through the following supplemental activities related to the parent grant's original aims. We will expand our genomic surveillance capabilities of SARS-CoV-2 variants in SJdRP and Panama. We will characterize both between-host and within-host diversity through deep sequencing using Illumina technologies and perform comprehensive phylogenetic studies using complete genomic sequences of SARS-COV-2 to infer patterns of virus spread and to inform hypotheses regarding variation in transmissibility and clinical outcomes (Aim 2e).",2021,2022,N/A,323943,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,Brazil,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15096,1R21AI158240-01,Elucidating the transcriptional mechanisms that control the expression of the SARS-CoV-2 receptor ACE2,"PROJECT SUMMARY There is a pressing urgency to understand the regulatory mechanisms that control the expression of ACE2, the cellular receptor for the new coronavirus SARS-CoV-2, in human cells under physiological and pathological conditions. The binding between ACE2 and the SARS-CoV-2 spike protein, along with proteolytic cleavage of ACE2, facilitates entry of the coronavirus into target cells, viral replication, and transmission. As such, ACE2 has been proposed as a key factor in virus infectivity and disease pathology. Although ACE2 is hijacked by SARS-CoV-2 in the pathogenesis of COVID-19, its primary physiological role is to counteract tissue injury and inflammation as part of the renin-angiotensin system (RAS). The expression of ACE2 is restricted to specific tissue-resident cell types, developmentally regulated, and highly responsive to physiological (e.g. sex hormones) and pathological (e.g. inflammation or virus infection) signals. By surveying the epigenetic landscapes at the human ACE2 locus in the major ACE2-expressing cell types, we identified a set of gene- distal cis-regulatory elements (CREs) displaying tissue-specific activity, consistent with putative cell type- specific enhancer elements for ACE2. The molecular basis for the tissue- and developmental stage-specific expression of ACE2 is unknown, and the regulatory mechanisms controlling ACE2 expression in response to physiological and pathological signals remain unexplored, highlighting a critical gap in knowledge. Without an in-depth understanding of the molecular and cellular pathways that control ACE2 expression, the genetic or pharmacological modulation of ACE2 as an approach to therapy for COVID-19 will likely remain unreachable. The objective of this project is to close a critical gap in our understanding of the transcriptional mechanisms controlling ACE2 expression under normal and pathological conditions. The central hypothesis is that ACE2 expression is controlled by combinations of tissue-specific CREs to recruit cell type-specific and/or signal- dependent transcription factors. This hypothesis has been formulated on the basis of the tissue-specific expression profiles of ACE2 in human cells, the presence of multiple gene-distal CREs demarcated by active chromatin signatures in ACE2-expressing cells, and the differential effects on ACE2 expression upon physiological or pathological stimulations. Guided by these findings, this hypothesis will be tested by two specific aims: 1) Determine the functional roles of tissue-specific cis-regulatory elements in controlling ACE2 expression and its responses to stimuli; 2) Identify and characterize chromatin regulatory complexes responsible for ACE2 expression by CRISPR/dCas9-mediated affinity purification. Together, by focusing on the validated entry receptor for SARS-CoV-2, our studies will not only advance our mechanistic understanding of critical aspects of viral susceptibility and post-infection pathology, but also establish a much-needed resource of candidate cis- and trans-regulatory factors required for ACE2 expression in human cells, thus facilitating ongoing development of innovative strategies to leverage ACE2 as targeted therapies against COVID-19.",2021,2023,N/A,441479,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15097,75N91019D00024-0-759102100001-1,Frederick National Laboratory for Cancer Research (FNLCR) Center for SARS-CoV-2 Serological Sciences,"The purpose of the National Cancer Institute's SARS-CoV-2 Serological Sciences Network (SeroNet) is to study the immune response to COVID-19 by developing and deploying serological assays of the highest specificity and sensitivity, expanding the national testing capacity for SARS-CoV-2 antibodies, and conducting research to develop understanding of immune responses to SARS-CoV-2. The FNLCR Center for SARS-CoV-2 Serological Sciences (the Center) is comprised of (1) Frederick National Laboratory (FNL) Serology Lab, (2) SARS-CoV-2 Serology Capacity Building Centers (CBCs), and (3) a Coordination Center that coordinates the activities of all SeroNet components. The Center's priority for the FNL Serology Lab will be for the development and validation of serological antibody assays, including ELISAs, point of care lateral flow tests, and virus neutralization assays. The Center will also develop and disseminate the National SARS-CoV-2 serology standard that includes positive and negative controls along with proficiency panel samples. The Center will also implement laboratory based serology assays and increase assay throughput capabilities within the FNLCR Vaccine, Immunity and Cancer (VIC) Program and the CBCs for use in viral immunology studies to understand longitudinal responses to natural infection or vaccination and to determine correlates of protection against infection in sero-epidemiology studies with the NIH/NCI and outside community. The Center's CBCs will build serological testing capacity by expanding testing to ~10K samples/week and conducting research in the natural history of infection or following vaccination to identify determinants of the immune response to SARS-CoV-2. The CBCs will also develop new assays as needed for deeper characterization of immune responses to the virus, vaccines, and correlates of protection. This may include development of assays for different functional aspects of the humoral responses, such as pseudovirus neutralization assays, determinants of antibody response and other relevant disease biomarkers. The data from these inter-collaborative studies, the U54 Serological Sciences Centers of Excellence, and U01 Research Projects in SARS-CoV-2 will be made available to the community through the Coordination Center within the Center.",2021,2026,N/A,85668587,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2021 +C15098,3P20GM113131-05S1,SARS-CoV-2 whole genome sequencing from large-scale campus testing and state-wide communities in NH--Center of Integrated Biomedical and Bioengineering Research (CIBBR),"PROJECT SUMMARY/ABSTRACT The Covid-19 pandemic has challenged public health systems throughout the world. Since October 2020, novel variants of concern of the SARS-CoV-2 virus have been identified and appear to be a significant concern for rates of infection, severity of disease, and the potential for variable responses to prior infection and/or vaccination. In the US-and especially in the state of New Hampshire-the number of SARS-CoV-2 genomes sequenced has been sparse. Furthermore, SARS-CoV-2 sequencing efforts have primarily been directed toward symptomatic individuals and/or contact tracing of special cases (e.g., hospital transmission). We currently lack knowledge in several areas including the temporal sequence and geolocation of the appearance of SARS-CoV-2 variants in regional communities; the correlation between incidents of viral outbreaks and SARS-CoV-2 variants; and the racial, ethnic, gender, and age susceptibility to infection (and severity of COVID-19 symptoms) by specific SARS-CoV-2 variants. In addition, as the U.S. enters a critical phase of the SARS-CoV-2 pandemic to develop herd immunity through prior infection and the vaccination program, we also lack an understanding of to what extent previously infected and/or vaccinated individuals are still susceptible to infection by SARS-CoV-2, and if so, what variants are infecting these supposedly ""protected"" individuals. The objective of this project is to determine the genomic sequence of a large majority of the SARS- CoV-2 variants identified in infected individuals in the state of NH and to apply this knowledge to better understand the likelihood that SARS-CoV-2 variants of concern increase the transmissibility of the virus, evade the immune systems of those previously infected, or result in a greater likelihood of infected individuals to experience clinical symptoms. The study population for this project consists of 12,000 stored human specimens previously confirmed by diagnostic tests to contain the SARS-CoV-2 virus, as well as newly identified specimens infected with SARS-CoV-2 as they become available during the project period. Preliminary whole-genome sequencing results document the quality of stored specimens as well as the ability to determine the lineage of SARS-CoV-2 variants present in the UNH congregate community and in the general NH population. Large-scale genomic surveillance of SARS-CoV-2 will permit correlating SARS-CoV-2 variant prevalence with available metadata (e.g., date of infection, geolocation, severity of outbreaks, symptomology, and characteristics of the sample population. Understanding the distribution and infectivity of SARS-CoV-2 variants will provide public health agencies with more accurate and specific information on public health measures that need to be enacted to control COVID-19 based on the types of SARS-CoV-2 variants present in specific populations, including those in congregate communities and previously infected individuals.",2021,2022,N/A,757077,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Disease susceptibility",2017 +C15099,1DP2MD017444-01,Community-Academic Partnerships to Address COVID-19 Inequities within African American Communities,"Abstract In a few months' time, the emergence of the coronavirus disease (COVID-19), a highly contagious disease resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sickened millions and killed hundreds of thousands of people in the United States alone. As with many other communicable and non- communicable diseases, African Americans disproportionately bear the burden of elevated rates of COVID-19- related morbidity and mortality. The rise in negative sentiments towards wearing masks in public, interpersonal and structural racism, and inability to shelter-in-place further exacerbate risk of SARS-CoV-2 exposure for members of vulnerable populations, including African Americans. With recent projections estimating that nearly 50,000 more Americans will die of COVID-19-related complications by December 2020, with at least 30% likely to be African American, it is clear that current public health efforts, which are overwhelmingly expert-driven and top-down, are failing. As such, innovative solutions that: 1) empower and equip communities to play an active role in promoting public health and responsiveness, 2) leverage community assets and multisectoral partnerships, and 3) facilitate a sense of unity and collective responsibility are sorely needed if we are to contain SARS-CoV-2 and eliminate COVID-19-related morbidity and mortality, particularly amongst those suffering disproportionately worse outcomes. Public health campaigns and non-pharmaceutical interventions (NPIs) that are community-driven and developed in collaboration with community members, public health agencies, and researchers may offer a more acceptable and effective approach that could enable the US to drastically reduce COVID-19 transmission and address individual and socio-structural barriers that lead to worse COVID-19-related outcomes among African Americans. Our study goals are to use a crowdsourcing contest to identify exceptional ideas that promote COVID-19 testing and encourage the public to adopt health- promotive behaviors. We will then conduct a randomized experiment to examine the impact of the contest on the targeted health-promotive behaviors. Next, in partnership with Project Grace, an academic-community partnership in rural NC, we will initiate an NPI called the Rapid Response Team, which will be a community- based contact tracing and case investigation program that will focus on identifying local COVID-19 infections in their communities, providing assistance and information regarding implementing safety protocols, and meeting existing needs of community members within a rural community in North Carolina by leveraging NCCARE360, a new digital, statewide coordinated care network intended to better connect individuals to local services and resources. Then, we will determine the feasibility, acceptability, and reach of the Rapid Response Team regarding contacting community members and linking them to local resources as needed, increasing COVID- 19 testing, and increasing the practice of the 3Ws among adults in rural, Eastern North Carolina.",2021,2024,N/A,1449000,Human Populations,Black,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions | Community engagement | Policy research and interventions,2021 +C15101,3UM1AI068614-15S2,"CoVPN 3005 - Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older","FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled ""A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older."" With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 - both monovalent and bivalent (""study vaccines"") in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines.",2021,2021,N/A,61429109,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2021 +C15103,3U01AI151814-02S1,SARS-CoV-2 genomic variant surveillance in human and non-human primate populations in Peru,"ABSTRACT Characterization of SARS-CoV-2 variants in Peru, which has one of the highest mortality rates in the world, has been limited and represents a significant knowledge gap that can be addressed through increased genomic surveillance activities. Located within the Amazon Basin, Iquitos was one of the first cities in Peru to experience the impact of the COVID-19 pandemic with devasting levels of transmission in March 2020, followed by one of the highest documented seroprevalence rates of anti- SARS-CoV-2 antibodies worldwide, only to have a second wave of transmission from January through March 2021. Utilizing human samples collected in and near Iquitos, the EpiCenter for Emerging Infectious Disease Intelligence (EEIDI) will sequence SARS-CoV-2 isolates and characterize variants from Peru and investigate their association with human disease severity and syndromes, reinfection, travel history, health outcomes, and patient demographics. We will also characterize isolates of SARS-CoV-2 variants from sampled animals, in particular non-human primate populations that closely interact with humans to investigate potential for spillback into future animal reservoirs. This work will ensure rapid and adaptive surveillance of existing and emerging variants, while improving an understanding of which variants are most likely to be involved in future outbreaks.",2021,2022,N/A,149998,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,Peru,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease susceptibility",2021 +C15104,1R01AI159182-01,Structure-guided and epitope-based design of potent and broadly neutralizing nanobodies for COVID-19 mucosal immunotherapy,"Project Summary The coronavirus disease 2019 (COVID-19) rapidly disseminated through the human population and became a global pandemic. Significant efforts have been put into developing vaccines or antibody therapies based on the spike glycoprotein of SARS-CoV-2. One challenge of such strategies is to identify conserved epitopes on the Spike and predict viral mutations that could diminish the effectiveness of the vaccine and immunotherapy. To date, over 20 variant of SARS- CoV-2 genome sequences have been reported. Therefore, structure guided and epitope based design are crucial to generate effective medicines for current and future outbreaks of SARS-CoV- 2 or related coronavirus. Nanobodies can recognize conserved epitopes on hypervariable pathogens. Here, we propose that anti-spike nanobodies can be utilized for rapid identification of protective epitopes to inform design of vaccine and therapeutics. Further, we hypothesize that potent and broadly protective nanobodies against SARS-CoV-2 can be developed as an inhaled prophylactic or therapeutic medicine. In this proposal, we will leverage our complementary strengths through a multi-disciplinary approach combining mucosal immunology, structural biology, and virology, to characterize the molecular interactions and differential specificities of a diverse panel of nanobodies against spike of SARS-CoV-2 and other members of the Betacoronaviruese family (Aim 1). A comprehensive list of conserved and non-conserved epitopes (Aim 2) will be used for structure-based design of potent nanobody multimers for in vivo characterization (Aim 3).",2021,2026,N/A,664782,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15105,1R21AI164043-01A1,Multi-dimensional comparison of differentially pathogenic coronaviruses (CoV) in human lung tissue,"PROJECT SUMMARY: SARS-CoV-2 is a novel coronavirus and the cause of the current global pandemic. This outbreak started in December of 2019 and has now spread over the entire world. SARS-CoV-2 is a respiratory pathogen that causes COVID-19, which has been the cause of more than 2.6 million deaths worldwide, with over 538,000 deaths in the US alone as of March 2021. The primary pathology caused by SARS-CoV-2 infection in humans is in the lungs. In this proposal, we seek to study the early events following coronavirus infection by infecting human lung tissue ex vivo. In order to understand the mechanism by which SARS-CoV-2 causes such severe disease outcomes, we will compare two coronavirus strains, SARS-CoV-2 (which is highly pathogenic) and NL63 (which is mildly pathogenic) in humans. In Aim 1, we will identify differences in viral replication kinetics, infected cell types, and the inflammatory response. In Aim 2, we will characterize the host response to infection using mass spectrometry-based proteomics. Understanding these complex virus:host components in a human system and how these differ between coronaviruses will lead to new hypotheses for in vivo susceptibility and identify new drug targets for therapeutic development.",2021,2023,N/A,253750,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C15106,1R01AI161175-01A1,The origin and future protective activity of SARS-CoV-2 RBD specific neutralizing antibodies,"PROJECT SUMMARY SARS-CoV-2 has infected over 138 million people and resulted in over 2.8 million deaths so far, with the expectation the pandemic will continue for many more months, and the virus will persist endemically for years, exacerbated by emerging variants of concern (VoC). Although several vaccines are being used wide-spread, it is unclear if they will be able to induce effective long-term immunity against emerging VoC. Highly effective anti- viral therapeutics for SARS-CoV-2 remain elusive, although several monoclonal antibodies (mAbs) targeting the Receptor Binding Domain (RBD) of the Spike (S) protein have been granted EUA for mild to moderate infection, their effectiveness against severe disease has not yet been evident. With the slow pace of global vaccination, limited anti-viral use/efficacy, and the emergence of antigenic drift variants, the trajectory of this pandemic and future resurgences of the virus is of great concern. Fundamental understanding of the mechanisms of inducing and sustaining protective humoral immunity to SARS-CoV-2 will be critical to its mitigation. The virus is now classified into several clades, numerous VoC emerging, and indications including our work and others that some of this antigenic drift is the result of the virus escaping from immune pressure and increased transmissibility. Drift within the RBD is of the utmost concern as it can enhance the infectivity of the virus and negate the activity of NAbs that may have developed from previous vaccination or infection. Numerous reports have emerged of repeated SARS-CoV-2 infections in patients, and breakthrough infections in fully vaccinated individuals, highlighting the imperfection of naturally acquired SARS-CoV-2 immunity. Utilizing our rationally designed RBD/RBD-ACE2 fusion protein variants, we have identified epitopic and phenotypic heterogeneity amongst RBD-specific human B cells and have isolated several potent RBD-specific human neutralizing monoclonal Abs (NmAbs) (IC50<50 ng/ml) against SARS-CoV-2 which are entering into a Phase 1/2 clinical trial using inhaled delivery in the coming months. We hypothesize that within RBD, the highly conserved regions (RBD-CR), epitopes desirable for mediating broad and potent humoral protection, are surrounded by variable regions (RBD- VR) that are structurally dynamic and highly susceptible to antigenic drift. Further, we hypothesize that RBD-VR mitigate the development of potent and broad RBD-CR specific humoral responses through their immunodominance and direct occlusion of RBD-CR. This RBD-CR/RBD-VR evolutionary dynamic is likely to regulate the sustained protection (or failure) of humoral responses against future viral variants. We will 1) define the ontological and phenotypic diversity of the human RBD-specific neutralizing antibody response, 2) define the dynamics of maintenance of ACE2 binding and immunological pressure on constraining RBD evolution, and 3) determine RBD Ab tolerance for and contribution to SARS-CoV-2 drift. Defining the limits of natural infection and vaccination induced RBD neutralizing antibodies to drive antigenic drift and confer protection from divergent SARS-CoV-2 viruses will inform the development next generation SARS-CoV-2 vaccines and therapeutics.",2021,2024,N/A,856430,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Pre-clinical studies,2021 +C15107,1R21EB031235-01,Development and Deployment of an Electrochemical Antigen Testing System for SARS-CoV-2,"Project Summary: The COVID-19 pandemic has highlighted the shortcomings of existing testing approaches for viral infection. Diagnosing active infections using PCR or other amplification strategies is constrained to centralized testing facilities that have limited capacity. New point-of-care molecular testing approaches, while providing a means to test outside of laboratories, have low throughput and turnaround times that are not compatible with widespread, rapid screening. Moreover, the use of nasopharyngeal swabs is highly problematic given the difficultly of acquiring and processing this sample type. Antibody tests integrated into lateral flow devices utilize a more tractable sample type and are effective for estimating infection rates, but are not useful for detecting active infections. In this proposal we describe a new viral detection approach that is rapid, amenable to massively decentralized testing, and provides a new means to perform viral infection assessment as a tool to combat the current COVID-19 pandemic and control future viral outbreaks. The new technology powering this approach is a breakthrough in reagentless sensing accomplished using electrochemical readout that will enable rapid screening for SARS-CoV-2 infection. The sensors will directly detect viral particles and viral proteins based on a unique signal transduction mechanism and can be used for in situ measurements inside of the mouth or in saliva samples. The fact that no external reagents are required makes this approach particularly amenable to decentralized on-demand testing. Project deliverables will include a screening system that will allow for direct SARS-CoV-2 detection from a saliva sample (without the generation of aerosols) in a time frame relevant at-home community screening. This will accelerate the availability of high-quality and real-time data to support a rapid response to better detect and manage COVID-19. In addition, the low cost and portable nature of the diagnostic device will allow for deployment to low- and middle-income countries to help prevent the rapid spread of COVID-19 within those populations. The rapid viral detection system will: 1) Provide an alternative to PCR-based testing and accelerate the availability of high-quality diagnostic information to allow Americans to better manage the pandemic; 2) Develop an effective intervention that will provide rapid, actionable diagnostic information on COVID-19 status; 3) Enable clinical studies that assess viral load as a function of medical countermeasures by facilitating serial and continuous monitoring of patients for SARS-CoV-2.",2021,2023,N/A,295888,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15108,1R01AI161829-01A1,ACE2-targeted PET radiotracers for investigating spatiotemporal distribution of SARS-CoV-2 organ injury and therapy response.,"PROJECT SUMMARY: The COVID-19 pandemic, caused by the new coronavirus SARS-CoV-2, has had a remarkable impact on public health worldwide with the largest number of cases and deaths reported in the United States. Improved understanding of COVID-19 will accelerate the development of effective therapeutics, which are necessary to fight SARS-CoV-2 including its new variants. The SARS-CoV-2 human receptor ACE2 is central to disease pathogenesis and potential therapies. This proposal focuses on the imaging and therapy of SARS-CoV-2 using a newly developed, ACE2-targeted PET radiotracer and S-protein neutralizing therapies. These therapies include PLGA nanoparticles bearing recombinant ACE2 (rACE2) and a monoclonal antibody (mAb) 5A6 recently developed at UCSF. Although the techniques and therapies proposed are directly applicable to SARS- CoV-2, they will also potentially apply to future coronavirus infections and other diseases driven by ACE2 suppression especially acute respiratory distress syndrome (ARDS). Therapies derived from ACE2 itself also have high impact in the context of SARS-CoV-2 variants that evade vaccines and mAb-based drugs. We recently identified a cyclic, [68Ga]-NOTA modified ACE2 inhibitory peptide ([68Ga]-NOTA-ACE2pep) as a PET radiotracer to study SARS-CoV-2 infection and its treatment in vivo. This radiotracer was developed with the goal of understanding the timing and location of ACE2 suppression in COVID-19, critical in treating infected patients and identifying disease in the lungs, heart, kidneys, gastrointestinal tract and central nervous system. ACE2-specific PET imaging will also help us understand the effects of rACE2/mAb therapies, whose development has lagged behind vaccine rollout. In this proposal, we will first optimize a radiosynthesis of an analogous 18F-labelled tracer namely [18F]AlF-NOTA-ACE2pep and validate its performance in vitro (Specific Aim 1). In Specific Aim 2, we use [18F]AlF-NOTA-ACE2pep to image ACE2 loss in transgenic mice and a COVID-19 murine model. Finally, in Specific Aim 3 we will develop nanoparticle-derived methods to deliver rACE2/ 5A6 and demonstrate suppression of SARS-CoV-2 infection, when therapy is administered around the time of exposure. This treatment effect will be shown in vivo using [18F]AlF-NOTA-ACE2pep. Our 3-year R01 proposal prioritizes methods and approaches that can be developed very quickly, in an effort to impact the COVID-19 pandemic as soon as possible. The principal investigators of this proposal are Drs. David M. Wilson, Robert Flavell, and Tejal Desai (UCSF) and Sanjay Jain (Johns Hopkins); as leaders in the field of infection imaging Drs. Wilson and Jain have worked extensively together. Key infrastructure is already in place at UCSF and Johns Hopkins for the fight against COVID-19. Specifically, Dr. Jain's BSL3 facility at Johns Hopkins is one of the few places in the world where the proposed PET-CT studies of SARS-CoV-2 infected animals can be performed. We will therefore harness the strengths of multiple productive laboratories at UCSF and Johns Hopkins to accomplish the proposed work.",2021,2024,N/A,828473,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2021 +C15109,3U19AI135964-04S2,Assessing SARS-CoV-2 Variant Evolution in Patients,"SARS-CoV-2, the cause of the COVID-19 pandemic, emerged from Wuhan, China, and rapidly spread around the world. A feature of the pandemic has been the repeated emergence of SARS-CoV-2 clades and variants of concern, some of which have been shown to have enhanced transmissibility. Other aspects of these lineages, however, remain unclear. The vast majority of the 3.75 million deaths caused by SARS-CoV-2 are the result of severe pneumonia. In these patients, ongoing SARS-CoV-2 viral replication in the lungs leads to slowly progressing pulmonary injury and subsequent respiratory failure. Yet our understanding of the genetic evolution of SARS-CoV-2 in the lungs is limited because of difficulties sampling the pulmonary alveolar space and in linking viral samples to robust and comprehensive clinical data. In this regard, the Successful Clinical Response in Pneumonia Therapy (SCRIPT) Systems Biology Center provides the ideal infrastructure to collect deep-lung viral samples and corresponding immune response and clinical metadata from patients with COVID- 19. We propose to leverage the clinical and research infrastructure of SCRIPT to study SARS-CoV-2 variants and intra-host adaptation. We will expand SCRIPT to link patient phenotypes with virus genotypes. Our hypothesis is that SARS-CoV-2 clades influence the severity of COVID-19 pneumonia and that viral diversity evolves in the lungs of patients experiencing severe pneumonia. To test our hypotheses, we will perform the following specific aims: Aim 1. We will determine whether specific SARS-CoV-2 clades are associated with greater disease severity or altered host response. We will sequence SARS-CoV-2 isolates from a biobank of a general pool of COVID-19 patients at our institution and from BAL samples of intubated patients with severe COVID-19 pneumonia to establish their genotypes. Associations between specific SARS-CoV-2 clades and disease severity and outcomes in both populations will be sought. Aim 2. We will examine the evolution of intra-host SARS-CoV-2 viral sequence changes over time in the lungs of patients with severe COVID-19 pneumonia. In a subset of patients with prolonged respiratory failure, we will sequence viral isolates and examine the host immune response using longitudinally collected serial BAL samples. These data will be used to quantify viral dynamics in the lung, to map the intra-host emergence of viral quasi-species, to characterize the host immune responses elicited by these changes, and to correlate these features with the clinical conditions of the patients. Aim 3. We will generate a computational model that integrates SARS-CoV-2 clade genome information with clinical and host immune response features to predict the severity of COVID-19 infections. Viral clade data will be integrated with measures of the host immune response (BAL fluid flow cytometry and cytokine levels) and patient clinical metadata to develop a comprehensive model that predicts which patients will develop especially severe COVID-19 disease.",2021,2021,N/A,749891,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease susceptibility | Disease pathogenesis",2021 +C15110,1R21AI157831-01A1,Blocking TMPRSS2 expression for prevention of SARS-CoV-2 infection,"Summary/Abstract SARS-CoV-2 has infected over 51 million and is responsible for the death of over 1.27 million people globally. Interventions to address both prevention and treatment are urgently needed. Infection of SARS-CoV- 2 requires the host serine protease TMPRSS2 to activate the virus spike protein for interaction with the host ACE2 receptor and entry into host cells. TMPRSS2 levels are significantly regulated by androgen receptor signaling in prostate cancer cells, but unknown in respiratory epithelial cells. Numerous inhibitors have been developed to target AR signaling. The toxicity, effective dosage, and side effects of these inhibitors have been well-documented. We hypothesize that reducing TMPRSS2 levels by blocking AR signaling will block activation of the spike protein of SARS-CoV-2 in respiratory epithelial cells, thereby preventing its entry into host cells in the respiratory system. Our preliminary data indicate that genetic and pharmacological inhibition of AR signaling suppresses TMPRSS2 levels, and an AR signaling inhibitor significantly inhibits pseudotype virus infection in prostate cancer cells. In this proposal, we will examine whether AR signaling inhibitors will suppress TMPRSS2 levels in respiratory epithelial cells leading to inhibition of TMPRSS2-catalyzed proteolysis of the SARS-CoV-2 spike protein in vitro, subsequently mitigating its infection efficiency. Next, we will investigate if targeting TMPRSS2 levels will inhibit SARS-CoV-2 infection through the respiratory route in vivo. In particular, we will examine the SARS-CoV-2 infection efficiency in mice deficient in TMPRSS2 or androgen production. We will investigate if AR signaling inhibitors will reduce TMPRSS2 levels in vivo, and mitigate SARS-CoV-2 infection in respiratory system. The goal of this proposal is to examine TMPRSS2 as a target and identify an effective drug from currently known AR signaling inhibitors to inhibit SARS-CoV-2 infection. Although SARS-CoV-2 vaccine is under development and might be effective, this study will provide a therapeutic treatment option of suppressing SARS-CoV-2 infection in the host, thus reducing the severity of COVID-19 symptoms and ultimately preventing deaths from COVID-19.",2021,2023,N/A,226500,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15111,3S06GM127980-03S1,ITCA ASU-Sequencing of Tribal Wastewater to Assess Coronavirus Variants,"PROJECT SUMMARY The COVID pandemic has been particularly detrimental for Tribal communities across the U.S., who have experienced mortality rates greater than any other race: American Indians have 256 deaths per 100,000 people compared to 150/100,000 for white Americans. Several factors have been suggested as contributors to elevated infectivity, including inadequate infrastructure and underlying health conditions. An additional consideration is the presence of SARS-CoV-2 variants within Tribal communities, of which little is known as COVID testing and vaccine distribution have been the priorities of Tribal Health Departments and COVID Response Teams. To determine if variants are present in Tribal communities, we propose to assess wastewater for excreted coronavirus variants, a non-invasive approach that will capture community-wide mutations more efficiently than sequencing clinical samples. Untreated wastewater samples (24-hour composites) will be processed and quantified for coronavirus using RT-qPCR for the E-gene of SARS-CoV-2. After confirmation of the presence of coronavirus, extracted RNA will be converted to cDNA and sequenced with primers that cover the entire 30kb genome. While we are particularly interested in the U.K., South African, and Brazil strains, we will also report if other U.S. and novel variants are detected in the selected Tribal communities. Nucleotide mutations will be translated and modelled in silico to determine if the polymorphism(s) result in amino acid mutagenesis and/or are mapped to key protein regions. Results will be returned to Tribal health administrators to determine if additional testing of clinical biospecimens is necessary. This NARCH project will provide critical and timely pandemic information to sensitive populations through scientific translation and collaboration with Tribal communities.",2021,2022,N/A,94364,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen | Disease surveillance & mapping",2018 +C15112,1R03AG071596-01,Mechanism of pulmonary vascular wall thickening in COVID-19,"Summary/Abstract Currently the world is suffering from the pandemics of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter host cells. So far, over five million people have been infected with SARS-CoV-2 and over 300,000 people have died of COVID-19 worldwide, causing serious health, economical, and sociological problems. The aging population with cardiovascular comorbidities is highly susceptible to be severely affected by and die of COVID-19. However, the mechanism underlying this increased susceptibility has not been defined. Lack of such knowledge interferes with the development of therapeutic strategies to prevent death by COVID-19. The long-term objective of our research is to define the pathogenic mechanism of the SARS-CoV-2 infection to identify new therapeutic targets to combat COVID-19. We recently identified the occurrence of pulmonary vascular wall thickening in patients infected with SARS-CoV-2 who died of COVID-19, but not in patients infected with SARS-CoV-1 or influenza virus. In this project, we will test the central hypothesis that the SARS-CoV-2 spike protein promotes cell growth signaling in lung vascular smooth muscle cells. This hypothesis is based on preliminary results obtained in my laboratory showing that (i) the treatment with recombinant SARS-CoV-2 spike protein (without the rest of viral components) strongly activates cell growth signaling (the activation of mitogen-activated protein kinase) in human pulmonary artery smooth muscle cells; (ii) the ACE2 receptor binding domain of SARS-CoV-2 spike protein alone is not sufficient to activate cell growth signaling; and (iii) SARS-CoV-2 spike protein increases the protein expression of ACE2. We plan to accomplish the objective by addressing the following specific aims: (1) Establish the uniformity of pulmonary vascular wall thickening in patients who died of COVID-19; (2) Determine the mechanism of SARS-CoV-2 spike protein-mediated cell signaling in pulmonary artery smooth muscle cells; and (3) Define the role of SARS-CoV-2 spike protein-mediated cell signaling in the COVID-19 pathology. This project is innovative because it will address a novel mechanism of the SARS-CoV-2 infection and pathogenesis and the role of pulmonary vasculatures in the pathology of COVID-19. Results of this project are significant because they are expected to contribute to the development of new therapeutic agents to reduce the death caused by COVID-19 that occurs largely in the aging population.",2021,2023,N/A,80496,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C15113,3R01ES031082-02S1,"Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunity","Project Summary COVID-19 caused by the novel coronavirus SARS-Cov-2 first emerged in December 2019 and was officially declared a pandemic by WHO in March 2020. During this time, COVID-19 has caused millions of cases and deaths across the world. While most cases are asymptomatic or present with mild respiratory and flu-like symptoms, a significant fraction of COVID-19 patients develop severe pulmonary complications, overproduction of inflammatory factors and other manifestations, leading in critical cases to multiorgan dysfunction, respiratory failure and death. Strikingly, recent evidence indicates that, besides the typical severe lung pathology, SARS-Cov-2 infection also promotes autoantibody production and other autoimmune manifestations in some patients. However, why other patients seem protected and the mechanisms for COVID-19-associated autoimmunity remain unknown. We hypothesize that autoimmunity development in SARS-Cov-2-infected patients depends on genetic predisposition but also on the history of the individual's exposure to environmental triggers, including crystalline silica, an abundant mineral often associated with autoimmunity. To test this possibility, in this supplemental application we propose experiments with mice expressing human ACE2, the receptor for SARS-Cov-2. These mice will be infected with SARS-Cov-2 at doses that induce low-level COVID-related pathology but no mortality, allowing long-term monitoring for autoimmunity. We will test the effect of the time of SARS-Cov-2 infection and airway exposure to crystalline silica on autoimmune manifestations in hACE2-expressing non-autoimmune and lupus-prone mouse models. In addition, we will examine how the dose of silica affects induction of autoimmunity in SARS-Cov-2-infected mice. The results will provide proof of concept that exposure to environmental agents may exacerbate COVID-19-associated inflammatory and autoimmune responses, creating the foundation for future studies to assess the effect of other environmental triggers, mechanisms of disease pathogenesis, and potential therapeutic interventions.",2021,2022,N/A,423965,Animals | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15114,3P51OD010425-60S1,Impact of pre-existing SARS-CoV-2 immunity on vaccination against new variants,"PROJECT SUMMARY The deployment of efficacious SARS-CoV-2 vaccines has prevented the death of millions of people. New SARS- CoV-2 variants that are more transmissible exhibit increased resistance to neutralizing antibodies elicited by either the current vaccine or by prior infection with the original strain. To address this, we have developed a 2nd generation COVID19 vaccine that employs a self-amplifying replicon RNA (repRNA) and is delivered using a novel nanolipid carrier formulation (LION) that can be rapidly scaled up and is more stable at warmer temperatures to support effective worldwide distribution. Our repRNA vaccine expresses a structurally intact receptor binding domain (RBD) immunogen (called SHARP) that matches variants exhibiting resistance to neutralization by current vaccines. Second generation vaccines like this one will be administered to people that are already pre-immune to earlier variants of SARS-CoV-2 due to prior immunization or infection but, to date, the impact of pre-immunity to the original variants on these new vaccines is not known. Pre-immunity may enable the new vaccines to induce even broader antibody responses against different variants. On the other hand, original antigenic sin (OAS), wherein the immune response to an infection preferentially recalls memory cells primed by the first antigenic exposure, could dampen efficacy of 2nd generation vaccines if upon exposure to the new variant, B cell responses primed by the original variant are preferentially recalled. To gain a better understanding of the impact of pre-existing immunity on 2nd generation COVID-19 vaccines, we propose a pilot study using a repRNA vaccine expressing SHARP to immunize macaques with pre-existing immunity to the original D614G variant due to prior immunization. Our goal is to determine if pre-immunity improves or, alternatively, dampens the immunogenicity and/or protective efficacy of 2nd generation vaccines designed to protect against new variants. These questions are best addressed in NHPs that closely model the repertoire of innate and adaptive immune responses in humans and can be challenged with SARS-CoV-2 to investigate the impact on protective efficacy and recall responses. Our Aims are: 1) Characterize the magnitude, specificity and type of immune responses induced in macaques pre-immune to the original D614G variant and boosted with a a repRNA vaccine expressing the B.1351 variant immunogen. 2) Investigate pathogenesis of B.1351 infection in pigtail macaques, protective efficacy of the repRNA B.1351 SHARP vaccine in pre-immune macaques, and immune correlates of protection. 3) Determine the impact of prior immunization with the original D614G variant on innate immune responses and their role in the immunogenicity and efficacy of the 2nd generation repRNA B.1351 SHARP vaccine. Knowledge gained on the impact of pre-immunity from this study will have broader implications for the development of this and other 2nd generation vaccines. If successful, this study will also support further development and evaluation of a trivalent repRNA SHARP vaccine that is more amenable for worldwide distribution than current mRNA vaccines and could provide broad protection against multiple variants.",2021,2022,N/A,499999,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease models | Characterisation of vaccine-induced immunity",1997 +C15115,1R01AI163395-01,Structure and Dynamics of the SARS-CoV-2 Spike Protein,"Summary The COVID19 pandemic may take 1-3 years and only fully subside once we reach herd immunity. Given the high mortality of COVID19, it is of critical importance to reach herd immunity through a vaccine. The viral spike glycoprotein (S) is central to our efforts for developing an effective vaccine immunogen. The S protein mediates viral entry into susceptible cells, is the primary target for antibodies, and is a widely used antigen in diagnostic kits. As such understanding the structure and dynamics of the S protein, and how antibodies engage it, is important to our response to COVID19. S consists of a trimer of S1/S2 dimers. S1 contains the receptor-binding domain (RBD) that interacts with receptor ACE2. S2 is further processed by proteases into S2' that mediates fusion. Structural insights into the S protein have been gained by single particle cryo electron microscopy (SP cryoEM) of a soluble trimer comprising most of the ectodomain, as well as by cryo electron tomography (cryoET) and SP cryoEM of native virus particles. These structural studies have revealed several distinct conformational prefusion states wherein the RBD domain points either up or down. Receptor ACE2 binds the RBD in the up conformation and stabilizes S in the `two-RBD-up' or `three-RBD-up' conformations. The observations of several distinct conformations at the EM level suggest that the S trimer exists in a conformational equilibrium. Real-time measurements of conformational dynamics of the S protein have not been performed. Many antibodies that bind and neutralize the S protein are being isolated from single B cells from recovered patients, or generated in mice, and their epitopes are being structurally characterized. Surprisingly, even though many antibodies clearly bind SARS-CoV-2 S, many do not neutralize the virus. Vaccine studies and clinical trials based on soluble RBD and S immunogens are under way. In general, they elicit antibodies and can protect from challenge in non-human primates and underscore our hope that a vaccine that develops antibodies against the S protein will be successful. However, the observation of non-neutralizing antibodies, a decline of antibodies in patients and worrisome evidence that antibody-bound coronavirus particles are responsible for the tissue-damaging inflammatory response seen in patients indicate that we need to know more about antibody mediated immunity against SARS-CoV-2. To address these challenges, the Mothes, Liu, Xiong and Blanchard laboratories will employ single molecule and in vivo imaging techniques to determine the structure and dynamics of ligand-free and antibody-bound SARS-CoV-2 S protein in the context of virus particles, and determine the fate of antibody-bound virus in vivo. Our work will inform active and passive immunization strategies against the COVID19 pandemic.",2021,2026,N/A,848007,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15116,1P01AI158571-01A1,Project 4: Computational panbetaCoV immunogen design,"Abstract - Project 4 SARS-CoV-2, a member of the genus Betacoronavirus (betaCoV), is the third major zoonotic outbreak of a highly pathogenic betaCoV in the last two decades. We propose to design vaccines to contribute to the global effort to counter the COVID-19 pandemic as swiftly as possible, and then to build on these designs to create panbetaCoV vaccines that could be used to rapidly contain outbreaks of future coronavirus zoonoses. To these ends, we will design both 1) Spike-targeted antibody vaccines, mindful of SARS-CoV-2 evolution as the pandemic progresses, and 2) conserved-region T-cell vaccine designs, to refocus CD8 T-cell response to regions in the proteome that cannot escape without a high fitness cost. These efforts toward pandemic vaccines will then be used as a foundation to extend our vaccine design strategies to counter the variability found among BetaCoVs, the highly diverse genus of CoVs that are found in bat populations. Based on our preliminary explorations of BetaCoV sequence diversity, we expect the design of a trivalent Spike-based vaccine using computational/bioinformatic and structure-based strategies to provide protection against the known range of diversity found in the subgenus Sarbecovirus. This includes both SARS-CoV-1, SARS-CoV-2, and the many related viruses isolated from bats and pangolins. If successful, these designs will be extended to cover Merbecovirus the subgenus that includes the MERS virus and other related viruses found in wild bats, rodents and cattle. Our Specific Aims are: Aim 1. Track the evolution of the SARS-CoV-2 during the COVID-19 pandemic. Aim 2. Design Spike vaccine antigens that optimize epitope exposure and betaCoV diversity coverage. Aim 3. Design T cell vaccines utilizing the most conserved regions in betaCoV. Our Spike-based computational vaccine designs will be based on our structural B cell mosaics strategy, and will be informed by Spike glycoprotein structures and molecular dynamic modeling, and will incorporate alignments of diverse Spike proteins. Using this approach we will design a trivalent set of complementary of proteins that optimally covers the natural diversity found among Sarbecoviruses in the bat reservoir. As we cannot predict with certainty the antigenic profile of viruses that may give rise to future zoonoses, we propose a two-pronged approach, and will simultaneously explore a conserved-region T-cell strategy that, although it might not block infection, could substantially mitigate disease, reducing both morbidity and transmission. Our T-cell vaccine designs will optimize the coverage of linear epitopes among BetaCoVs with a trivalent vaccine mix using our computational design strategy called Epigraphs. By focusing on the most conserved regions in the betaCoV proteome, we can more readily cover the broad spectrum of BetaCoVs diversity than in the more diverse Spike.",2021,2024,N/A,1863181,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C15118,1R56HL159712-01,TMPRSS2 as a potential target for treatments of COVID-19 and respiratory infectious viruses in lung,"Project Summary In December of 2019, a novel coronavirus, now referred to as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), struck Wuhan, China and unleashed the current coronavirus disease (COVID-19) pandemic. There are currently no medications or vaccines proven to be effective for the treatment or prevention of COVID-19. There is an urgent need to identify effective therapeutic options: a vaccine and/or drugs that can effectively cure the disease. Although a vaccine will be the ultimate way to combat the virus as a community, antivirals are likely to be developed and approved faster, especially since a broadly available and effective vaccine is likely years away. Antivirals would hugely benefit the population that is currently affected by the virus, helping individuals recover and reducing the number of deaths. Antivirals would also reduce the number of positive carriers and thus curb the spread of the disease. This proposal aims to develop an efficient antiviral to impede the virus' entry into cells, specifically into lung alveolar type II (AT2) cells, the stem cells of the distal lung. Thanks to recent studies, we know which ""door"" (a receptor called ACE2) and ""key"" (a protease called TMPRSS2) the virus uses to enter cells. Our goal is to remove the ""key"" so the virus cannot open the ""door"" and enter host cells. We will use a recently developed 3-dimensional (3D) in vitro lung organoid model that recapitulates many aspects of lung structure and the cellular environment and that has been used to study respiratory viruses, including SARS-CoV-2. This system represents tissues better than cell lines, but offers the benefit of being less complex than tissue explants or animal models. In addition, we have generated a panel of highly sensitive and specific mouse monoclonal antibodies (mAbs) directed against TMPRSS2. In preliminary studies, the lead TMPRSS2 mAb, AL20, shows no signs of cytotoxicity with a trend towards inhibition of SARS-CoV-2 pseudovirus entry in cell lines. Furthermore, we have identified at least two serine protease inhibitors (serpins) that form complexes with TMPRSS2, and the presence of these complexes is inversely correlated with the SARS-CoV-2 infection rate. These findings lead to our hypothesis that targeting TMPRSS2 can inhibit SARS-CoV-2 viral entry and spread. To test our hypothesis, we will first test the efficacy of AL20 for blocking the entry of SARS-CoV-2 into AT2 cells in lung organoids, and elucidate the underlying mechanisms. We will then evaluate the effects of serpins on TMPRSS2 activity and SARS-CoV-2 viral entry and spread. Finally, to explore the feasibility of advancing AL20 to human trials, we also propose to humanize and test AL20 in available K18-hACE2 mice. This transgenic strain expresses human ACE2, regulated by the KRT18 promoter that directs expression to lung epithelia, to provide the pre-clinical data necessary to test the feasibility of advancing to human clinical trials. These studies will provide critical insights into the mechanisms whereby TMPRSS2 regulates SARS-CoV-2 entry, and suggest potential therapeutic candidates against COVID-19. The proposed work has the potential to impact the lives of millions of individuals affected by COVID-19 and other respiratory viruses, such as influenza A, that use TMPRSS2 to enter cells.",2021,2022,N/A,421219,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2021 +C15119,3P20GM103395-20S3,Surveillance of SARS-CoV-2 in Alaska,"Project Summary: To date (3/23/21), Alaska has suffered over 58,000 cases of COVID-19, 1,318 hospitalizations, and 306 deaths. Alaska is a designated Primary Care Health Professional Shortage Area. Likely driven by health disparities, the COVID-19 fatality rate among American Indian/Alaska Native (AI/AN) residents of Alaska is nearly two times higher than the population of Alaska as a whole (71 v. 47 per 100,000; Alaska DHSS Bull. 1/29/21), a pattern observed in AI/AN population nationwide (CDC MMWR 12/11/20). Even with these challenges, Alaska has one of the lowest COVID-19 hospitalization and fatality rates overall, and one of the highest rates of COVID-19 vaccination. Sequencing of SARS-CoV-2 genomes has emerged as the key technology for analyzing spread of SARS-CoV-2 lineages, including detection of VOC that may cause more rapid spread, more severe disease, or reduce vaccine efficacy. Importantly, through early capacity-building by the Alaska DHSS Public Health Lab (PHL), in partnership with the University of Alaska and Alaska INBRE, over 500 SARS-CoV-2 genomes have been sequenced and released (GISAID), including recent cases of B.1.1.7, B.1.429, and P.1 variants of concern (VOC). Thus, it is important to understand the geographical and temporal spread of SARS-CoV-2 lineages in the state, and specifically in the AI/AN population. In response to this NIGMS NOSI, the Alaska INBRE (IDeA) program is proposing to extend the genomic surveillance for SARS-CoV-2 lineages and variants in Alaska, with a team of University of Alaska researchers (at UA-Fairbanks and UA-Anchorage), in collaboration with the Southcentral Foundation (SCF) and Alaska Native Medical Center (ANMC) AI/AN health networks, and support from other partners including the Alaska DHSS PHL and CDC Arctic Investigations. The project goals are (1) Prospective genomic sequencing of VOC and VOI in Alaska and comparison to other regions; (2) Prospective genomic sequencing of VOC/VOI in AI/AN health networks to understand COVID-19 disparities; and (3) Geographic and temporal analysis of SARS-CoV-2 in Alaska to inform epidemiological understanding. We will leverage both short-read (Illumina) and long-read (Nanopore) sequencing platforms, and bioinformatics expertise built by Alaska INBRE, to analyze SARS-CoV-2 genomes with samples provided by Alaska DHSS/PHL, and specifically in AI/AN (SCF and ANMC served) populations. Data will be released for meta-analyses to provide genomics perspective to epidemic tracing, understanding of spread of novel lineages, and impact of health disparities.",2021,2024,N/A,128440,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease susceptibility",2001 +C15120,1R43AI165089-01,Developing a Thermostable SARS-CoV-2 RBD-particle Vaccine,"PROJECT SUMMARY The coronavirus disease 2019 (COVID-19) global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is unprecedented in our lifetime and has caused major social, economic and human suffering. Globally, there have been 76,858,506 confirmed cases, leading to 1,711,498 deaths as reported by the WHO through December 2020. The rollout of FDA-authorized Pfizer (-80 ˚C storage) and Moderna (-20 ˚C storage) vaccines has highlighted the challenges posed by low requisite storage temperatures. Elimination of cold chain requirements for emerging vaccine solutions could facilitate distribution and provide considerable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposes to investigate a lyophilization strategy for its novel vaccine adjuvant platform that induces spontaneous antigen particles, using the receptor-binding domain (RBD) of the SARS CoV-2 spike (S) protein. We were amongst the first to show that a liquid form of RBD particles potently increases SARS-CoV-2 neutralizing antibodies by orders of magnitude compared to the soluble antigen. Our vaccine platform induces the particle formation of well- characterized his-tagged antigens by simple admixing with liposomes that contain small amounts of cobalt porphyrin-phospholipid (CoPoP) and the clinical adjuvants monophosphoryl lipid A and QS-21. CoPoP liposomes give rise to rapid antigen particleization that is stable in biological media. In this collaborative Phase I SBIR proposal, we will assess the impact of lyophilization on the conformational and thermal stability of the resulting lyophilized vaccine, evaluated by biochemical and biophysical assays, and its efficacy will be assessed by functional immunogenicity in mice. This project will assess the feasibility of breaking the cold-chain requirements for a next-generation particle vaccine system, which could be critical for resource-limited settings. In collaboration with the Texas Biomedical Research Institute (TBRI), a transgenic mouse model for SARS-CoV- 2 infection will be used to study the thermostability on protection induced by the lyophilized, RBD particle vaccine. 1",2021,2023,N/A,299991,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies | Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2021 +C15121,3UM1AI148574-02S2,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU) - DMID 21-0012,"PROJECT SUMMARY This supplement proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) research to be carried out at the NYU VTEU. We will participate in the implementation of in DMID protocol 21- 0012, ""A Phase 1/2 Study of Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) after Receipt of EUA Vaccines."" This Phase 1/2 study will evaluate the safety, tolerability, immunogenicity of different SARS-CoV-2 vaccine delayed boost at >12 weeks. This study will be composed of two different cohorts: 1. A cohort of persons previously vaccinated with an EUA vaccine who will be boosted with a homologous or heterologous vaccine strain on a homologous or a heterologous platform; and 2. A cohort of persons who are prospectively vaccinated with EUA standard dosing and who will be available for rapid assessment of a heterologous boost at some point in the future.",2021,2025,N/A,1341481,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial | Characterisation of vaccine-induced immunity,2021 +C15122,1R21AI163924-01,Functional characterization of SARS-CoV-2 myeloid cell receptors as an immunopathogenic mechanisms of COVID-19,"Project Summary The rapid spread of SARS-CoV-2 and the resulting Coronavirus Disease 2019 (COVID-19) pose a global pandemic. SARS-CoV-2 and its family members share some puzzling, unique pathological features, most notably acute respiratory distress syndrome (ARDS), cytokine release syndrome (CRS), and lymphopenia, despite excessive myeloid cell-dominant inflammation, which has been correlated with COVID-19 severity. How the virus engages and dysregulates the immune system is currently unknown; although angiotensin-converting enzyme 2 (ACE2) is the canonical SARS-CoV-2 receptor, immune cells, particularly myeloid cells, express little, if any, levels of ACE2 despite evidence for direct viral engagement. Based on our extensive experience in the discovery and characterization of immune-modulatory receptor-ligand interactions, we sought to address how SARS-CoV-2 interacts with myeloid cells, which play essential roles in both virus innate sensing and the modulation of host immunity, by developing a myeloid cell receptor-focused ectopic expression screen. In ongoing experiments, we have identified several novel glycan-dependent host interaction partners for SARS-CoV-2 Spike (S) protein, including several C-type lectins and Tweety Family Member 2 (TTYH2). Pulmonary single-cell RNA sequencing (scRNA-seq) analysis in COVID-19 patients indicates a myeloid cell-dominant expression of these receptors as opposed to ACE2. In the preliminary studies, we have shown that these molecules interact mostly through regions outside of the ACE2 receptor-binding domain (RBD), suggesting that they may provide a novel function outside of virus entry. Although these receptors do not support the active replication of authentic SARS-CoV-2, the direct virus-myeloid cell engagement induces a robust pro-inflammatory response, which is blocked by receptor-decoy proteins and a picomolar-affinity anti- spike bispecific nanobody that also blocks virus infection through ACE2. Together, our findings provide the first evidence for direct immune modulation by SARS-CoV-2, potentially targeted for therapeutic benefit. Given these findings, we hypothesize that novel SARS-CoV-2 virus-receptor interactions in myeloid cells constitute a pathogenic pathway for COVID-19, serving as signaling receptors that directly drive myeloid cell dysregulation. These new direct virus-immune interactions may also have heretofore unexplored functions to affect other cells indirectly. These hypotheses will be addressed within the following Specific Aims: (1) to determine the functional contribution of each myeloid cell receptor in the induction of pro-inflammatory responses upon SARS-CoV-2 engagement, and (2) to determine the role of these interactions in the dysregulation of adaptive immunity and SARS-CoV-2 trans-infection through ACE2 receptor. Our study on novel virus myeloid cell receptors that govern aberrant immune responses would greatly contribute to our understanding of COVID- 19 pathogenesis, revealing new therapeutic targets against COVID-19 for the benefit of humanity at large.",2021,2023,N/A,254250,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C15123,3U54GM115677-06S2,RI-Center for Clinical and Translational Science,"SUMMARY Until there is widespread suppression of COVID-19, SARS-CoV-2 testing will remain an essential public health tool to monitor infection patterns and address outbreaks, especially in vulnerable populations. To date, the primary focus in public health has been on reduction of COVID-19 cases in the adult population, who experience higher mortality and complications compared to the pediatric population. Nonetheless, it has been noted that COVID-19 is impacting the health, safety, and well-being of children and their caregivers. Furthermore, there are limited reports on SARS-CoV-2 testing or COVID-19 vaccinations among children and youth with special healthcare needs or their caregivers. In collaboration with community partners, this RADx-UP Phase II project will enhance a statewide system to monitor COVID-19 testing and vaccination patterns to guide improvements in access to testing and vaccine uptake among high-risk pediatric populations, defined as those who either live in vulnerable areas or with special healthcare needs. This RADx-UP Phase II project will build on our previous work to leverage the unique infrastructure of CurrentCare, the Health Information Exchange (HIE) in Rhode Island (RI), which connects data across the entire RI healthcare ecosystem, to obtain clinical data for most people receiving care in RI including SARS-CoV-2 test results and vaccinations. A major objective of this project is to quantify the impact of vaccination on vulnerable populations, focused on children, in near real-time. We are uniquely positioned to build on our explanatory sequential mixed methods design to combine HIE quantitative data with focus group and interview data (from both community members and providers in community health clinics) to further address challenges with testing and vaccination. The specific aims of this project are to: (1) Identify vaccination rates relative to COVID-19 positivity rates for high-risk pediatric populations; (2) Determine barriers to SARS-CoV-2 testing and community hesitancy to COVID-19 vaccination; and (3) Implement community-based approaches to increase testing and vaccination rates for high-risk children. In accomplishing these aims, our approach is designed around community health teams, who will facilitate the improvement of SARS-CoV-2 diagnostic testing and work with community members to understand and address vaccine hesitancy. Community health teams are widely accepted lay heath educators who have demonstrated their effectiveness in addressing community health needs. We will develop and integrate culturally congruent tools to support understanding of vaccination and possible side effects, promote conversations that help individuals move to vaccine acceptance, help with scheduling of subsequent vaccination doses, as well as continue support for access to testing and post-testing guidance. This RADx-UP Phase II project will expand the community-based infrastructure that we have developed in Phase I for enabling structured, longitudinal relationships with underserved patient populations.",2021,2023,N/A,1091210,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15124,1P01AI165077-01,PanCorVac (Center for Pan-Coronavirus Vaccine Development),"SUMMARY Most of the vaccines currently approved or in development against the pandemic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus target immunodominant, strain-specific epitopes in the SARS-CoV-2 spike (S) protein and are therefore not expected to confer protection against other coronaviruses. Accordingly, the NIAID announced NOT-AI-21-002, which calls for the ""development of prophylactic vaccines to provide broad and durable protection against coronaviruses, especially SARS-CoV-2 and others with pandemic potential"". In response to this call, we assembled the Pan-Coronavirus Vaccine (PanCoVac) consortium to develop and test novel pan-coronavirus vaccines. Research Project 1 (RP1; Design and evaluation of pan- CoV vaccines) uses two strategies to develop broadly protective coronavirus vaccines: (i) Focus immune responses away from the immunodominant epitopes in the head region of S and towards the more conserved, immune-subdominant epitopes in the stem region of S; and (ii) Refocus immune responses from the variable immunodominant epitopes towards more conserved epitopes in the head region of S. For each strategy, several innovative approaches will be used. Novel antigens will be presented by virus-like particles based on a self- assembling bacteriophage coat protein (a highly immunogenic platform). The candidate vaccines will be tested for their immunogenicity and protective efficacy against different coronaviruses in an animal model. Selected candidates will be tested in a second animal model, and with an mRNA lipid nanoparticle platform. Additional studies will test the durability of immune responses and the effect of vaccination on virus transmission. Samples from vaccinated animals will be provided to Research Project 2 (RP2; Immunological responses to pan-CoV vaccines) for a detailed assessment of B- and T-cell responses. First, RP2 will continue its ongoing efforts to generate and characterize panels of SARS-CoV S-specific mAbs, which will be used in RP1 to help characterize and prioritize vaccine candidates. Moreover, ""Ig-omics"", which involves single-cell technologies allowing high- throughput analysis of B-cell responses, phenotypes, immunoglobulin (Ig) repertoires and mAbs that react to several coronaviruses (a technology developed by one of the RP2 investigators), will be used to characterize B cell-mediated immunity and mAb specificity induced by the candidate vaccines. RP2 will also test (and compare with data from a human cohort study) the ability of the candidate vaccines to elicit responses to cross-reactive CD4 and CD8 T cell epitopes. In particular, recently developed novel methods will be used to characterize and compare the T-cell repertoires upon infection and vaccination. An Administrative Core will oversee and manage all financial and administrative aspects of the consortium. Our proposed research draws strength from a multi- institutional team of experts in molecular virology, structural biology, nanobiotechnology, and B- and T-cell immunology.",2021,2024,N/A,7000324,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Pre-clinical studies | Characterisation of vaccine-induced immunity,2021 +C15125,272201600013C-P00018-9999-10,MICROBIOLOGY AND INFECTIOUS DISEASES BIOLOGICAL RESEARCH REPOSITORY (MID BRR) - SARS-CoV-2 THERAPEUTICS RESEARCH RELATED ACTIVITIES,"This contract provides unique and quality-assured infectious reagents and resources to the scientific community for use in basic research and product development. The scope of this contract includes the acquisition, authentication, production, preservation, storage, and distribution of research and reference reagents to the research community. These reagents span the pathogens in the Division of Microbiology and Infectious Diseases portfolio, and include the National Institutes of Allergy and Infectious Disease (NIAID) Category A, B and C Priority Pathogens and emerging infectious diseases.",2020,2020,N/A,3008705,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,,,2020 +C15126,3U54GM104940-06S2,Health Disparities and SARS-COV-2 Evolution: A Focused Viral Genomics Study,"Health Disparities and SARS-CoV-2 Evolution: A Focused Viral Genomics Study Project Summary/Abstract We hypothesize that prolonged COVID19 illness, re-infection, and/or post-vaccine infection in patients with chronic conditions are associated with specific SARS-CoV-2 lineages or mutations, and that increasing the awareness of the potential danger posed by variants of concern will improve testing adherence and variant tracking. We propose to use our established FDA- authorized COVID19 sequencing platform in combination with innovative data analytics and clinical bioinformatics as well as our BMI and community engagement KCAs. Our proposal addresses four of the priority areas indicated by NOT-GM-21-031, specifically: • Are there different variants present in the study population, and how has the number of cases caused by different variants changed over time in the study population? • How are different variants distributed among different racial, ethnical, gender, and/or age groups? • Are specific variants associated with different levels of manifestation of COVID19 symptoms? • Do vaccinated study participants still acquire the SARS-CoV-2 virus, and if so, what variants do they carry? We propose these Specific Aims: Specific Aim 1. To improve surveillance of COVID19 by integrating SARS-CoV-2 sequencing and clinical data with a focus on under-represented, vulnerable and remote populations. Using highly automated processes, we will identify variants/mutations associated with clinical phenotypes, including prolonged asymptomatic/antibody-positive individuals, re-infected, and vaccinated populations. All trend data will be integrated in the AWS cloud where it can be accessed by relevant stakeholders including testing and vaccine program partners. Specific Aim 2. To develop and validate simulation models that incorporate SARS-CoV-2 genetic data with clinical outcomes to predict COVID19 case severity in Louisiana by region as vaccination levels increase. Specific Aim 3. To design and deploy culturally and linguistically appropriate outreach material on SARS-CoV-2 and determine whether increased knowledge of the potential danger of adaptive mutations improves acceptance of testing and vaccination.",2021,2022,N/A,737607,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Disease susceptibility | Prognostic factors for disease severity | Community engagement",2012 +C15127,3UM1AI148452-02S6,Vanderbilt Vaccine and Treatment Evaluation Unit - DMID 21-0004,"Program Director/Principal Investigator (Last, First, Middle): Creech, Clarence B Supplement Abstract Observational, Prospective Cohort Study of the Immunogenicity and Safety of SARS-CoV-2 Vaccines Administered during Pregnancy or Postpartum and Evaluation of Antibody Transfer and Durability in Infants. This project supports specific aims 2, 3, and 4 from the Vanderbilt UM1 application and is consistent with the terms of award. More specifically, the purpose of this activity is to evaluate the immunogenicity and safety of SARS-CoV-2 vaccines administered during pregnancy or post-partum and evaluate antibody transfer. Specific Aim 2: Conduct multi-site and single site research evaluating the safety, efficacy, and immunogenicity of novel interventions. We propose a single site at Children's Hospital of Philadelphia that will evaluate the immune response to COVID vaccines in pregnancy Specific Aim 3: Evaluate immune responses resulting from natural infection or vaccine administration. Central to this work will be the evaluation of immune responses to a COVID vaccine candidate. Specific Aim 4: Train future leaders in vaccinology and clinical trials. Similar to other studies conducted for COVID thus far, junior faculty and fellows will be trained in vaccine-related clinical studies and pandemic responsiveness. This request is to support COVID-19 clinical research, including site preparation, study implementation, and enrollment of participants in the above COVID-19 clinical research study. Work will include but is not limited to: site preparation activities; protocol development/revision; clinical study activities; laboratory processing and storage of samples; quality oversight; and manuscript development, as appropriate. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page",2021,2023,N/A,658548,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Urban Population/Setting,Pregnant women | Other,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Immunity | Phase 2 clinical trial | Characterisation of vaccine-induced immunity,2021 +C15128,3UM1AI148574-02S1,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU) - DMID 21-0004,"PROJECT SUMMARY This is an observational, non-interventional, prospective cohort study designed to collect clinical information and specimens to evaluate the immune responses from approximately 2,000 study participants following maternal receipt of licensed or EUA SARS-CoV-2 vaccines. Pregnant and postpartum individuals and their infants will be screened for study interest and eligibility and enrolled. Study participant groups are as follows: Approximately 2,000 study participants will be enrolled into one of four subject groups:  Group 1: Individuals who receive a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2) vaccine during pregnancy (up to150 individuals per vaccine type)  Group 2: Individuals who receive a SARS-CoV-2 vaccine postpartum (up to 50 individuals per vaccine type)  Group 3: Infants of individuals who receive vaccine during pregnancy (approximately 150 infants per vaccine type)  Group 4: Infants of individuals who receive vaccine postpartum (approximately 50 infants per vaccine type) Primary objectives are: • Immunogenicity: To describe the kinetics and durability of maternal serum antibodies following receipt of SARS-CoV-2 vaccine in individuals vaccinated during pregnancy, by vaccine type and platform. • Immunogenicity: To describe the transplacental antibody transfer of SARS-CoV-2 antibodies among individuals vaccinated during pregnancy, overall and by vaccine type and platform. • Immunogenicity: To describe the kinetics and durability of serum SARS-CoV-2 antibodies in infants of mothers vaccinated during pregnancy, by vaccine type and platform.",2021,2023,N/A,625430,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15129,3UM1AI148689-02S4,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site: CoVPN 3004,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. In the past 17 months, a key area of interest at NIAID has been discovery of safe and effective protective measures, including vaccines, for persons at risk of COVID-19. This proposal describes the implementation of a critical protocol in that arena, namely the Pediatric expansion of the phase 3 pivotal efficacy study of the Novavax recombinant spike protein vaccine with M Matrix adjuvant. The project's primary objectives are (1) to evaluate the efficacy of a 2-dose regimen of SARS-CoV-2 rS adjuvanted with Matrix-M1 compared to placebo against PCR-confirmed symptomatic COVID-19 illness diagnosed ≥ 7 days after completion of the second injection in the initial set of vaccinations of adolescent participants 12 to < 18 years of age; and (2) to describe the safety experience for the vaccine versus placebo in adolescent participants (12 to <18 years of age) based on solicited short-term reactogenicity by toxicity grade for 7 days following each vaccination (Days 0 and 21) after the initial set of vaccinations. Multiple additional objectives are also being evaluated. The design is a Phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants ≥ 18 years of age (Adult Main Study) with a Pediatric Expansion (This proposal is for the Pediatric Expansion). In the Pediatric Expansion, adolescent participants 12 to 17 years of age will be enrolled without stratification. Participants are followed for 2 years for safety, tolerability, efficacy, and immune responses. The expected sample size will be 3000 adolescents: 2000 will receive vaccine first and 1000 will receive placebo first. After 6 months, there will be a double-blind cross over. This study is expected to contribute the data necessary to allow for authorization of this vaccine in 12 to 17 year-olds in the US.",2021,2022,N/A,509201,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 3 clinical trial,2021 +C15130,1R43HL158409-01A1,A PTP4A3 inhibitor for SARS-CoV-2-mediated acute lung injury,"The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SAR-CoV-2, like other coronaviruses, infects human airways and enters cells via its S (Spike) protein, which binds to the human angiotensin-converting enzyme 2 (ACE2) and is primed by the host serine protease TMPRSS2. Both ACE2 and TMPRSS2 have been observed on pulmonary microvascular epithelium and endothelium. A subset of COVID-19 patients develop acute respiratory distress syndrome (ARDS) and subsequently septic shock and multi-organ failure; about half will die. The clinical worsening in the later phases of COVID-19 are thought to result from Spike protein binding to the pulmonary microvascular endothelium and epithelium, which leads to a damaged respiratory tract and ultimately a systemic inflammatory response or cytokine storm. There are currently no FDA-approved drugs/therapeutics that treat the pulmonary damage and ARDS associated with COVID-19. KeViRx is proposing to develop an entirely new therapeutic strategy that prevents or mitigates the initial pulmonary damage and halts the lethal cytokine storm. Our lead compound, KVX-053, is a reversible, selective, allosteric inhibitor of PTP4A3 phosphatase with excellent in vivo pharmacokinetic properties and drug-like properties. Moreover, mice tolerated multiple exposures to KVX-053 In culture KVX-053 was not cytotoxic to human ovarian epithelial cells or fibroblasts at concentrations up to 25 µM. Surprisingly, we found that KVX-053 markedly enhanced the pulmonary microvascular barrier function before and after injury caused by bacterial lipopolysaccharide and vascular endothelial growth factor. PTP4A3 phosphatase is known to be induced in lung cells 12 h after SARS-CoV infection and to control cytokine release. The overall hypothesis of this Phase I SBIR application is that the PTP4A phosphatase family has a sentinel role in the acute lung injury of ARDS and the systemic inflammatory response in COVID-19.The goal of the project is to repurpose KVX-053 for use in individuals with COVID-19 and for future pandemics involving acute lung injury. This Phase I SBIR application has three proof-of-concept Specific Tasks. Specific Task 1 will determine the ability of a novel, potent, allosteric, small molecule PTP4A3 inhibitor, KVX-053, to block SARS-CoV-2 Spike 1 protein-mediated loss of pulmonary endothelial barrier function and cytokine release in vitro. Specific Task 2 will determine the ability of KVX-053 to block SARS-CoV-2 Spike 1 protein-mediated pulmonary alveolar epithelial barrier function and cytokine release in vitro. Specific Task 3 will determine the ability of KVX-053 to inhibit acute lung injruy in mice caused by the SARS-CoV-2 Spike 1 protein.",2021,2022,N/A,252208,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15132,3R24OD026440-03S1,Live imaging of SARS-CoV-2 infection in novel humanized mice,"PROJECT SUMMARY The SARS-CoV-2 pandemic is an unprecedented challenge for the global health community, and there is urgent need to understand the pathogenesis of SARS-CoV-2 and emerging viral variants. The pathology associated with SARS-CoV-2 infection ranges from asymptomatic to severe, in some cases fatal disease that correlates with inflammatory cell death during infection, activation of the immune system and release of inflammatory cytokines or a ""cytokine storm"". Unfortunately, available animal models of SARS-CoV-2 infection do not fully recapitulate the human immune response to viral infection due to multiple differences in genomes, molecular and metabolic pathways, and immune system regulation. The goal of our supplemental proposal in response to PA-20-272 is use a panel of translational humanized mouse models developed by Dr. Leonard Shultz at The Jackson Laboratory to study the clearance of SARS-CoV-2 and the variants that are continually emerging, and for the testing of human-specific therapies that will mitigate the pathology associated with COVID-19. In addition, we will use a novel in vivo bioluminescence imaging approach to monitor the kinetics of SARS-CoV-2 spread and clearance in real time in vivo. We have assembled a team of investigators with extensive experience in 1) creating new humanized mouse strains (Dr. Leonard Shultz at The Jackson Laboratory), 2) engrafting human immune systems into immunodeficient mice (Drs. Dale Greiner and Michael Brehm at UMass), 3) the study of human viral pathogens (Dr. Priti Kumar at Yale University), and 4) expertise in imaging virus infection in real time in vivo (Dr. Pradeep Uchil at Yale University). We will leverage the resources of The Jackson Laboratory to facilitate the rapid distribution of effective models to the scientific community, uniquely positioning our group to contribute quickly to the knowledge of SARS-CoV-2 biology. Dr. Shultz has generated new models of NSG mice expressing human ACE2 and will provide these mice to Dr. Kumar and to Drs. Brehm and Greiner. Drs. Brehm and Greiner will engraft the mice with human UCB CD34+ HSCs and will provide engrafted mice to Dr. Kumar's laboratory. Drs. Kumar and Uchil will perform the infection studies with SARS-CoV-2 and its variants in both non-human immune engrafted (Specific Aim 1) and human immune engrafted mice (Specific Aim 2) and analyze the kinetics of virus clearance in real time using novel bioluminescent imaging technology. In addition, overall mouse health, viral load in tissues and inflammatory cytokines will be monitored. We will validate the optimal SARS-CoV-2 infection protocols with the NSG mouse stocks. Ultimately, these studies will determine the clearance and pathogenesis of SARS-CoV-2 and variants in the absence or presence of a human immune system.",2021,2023,N/A,499998,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Disease models | Pathogen morphology, shedding & natural history | Pre-clinical studies",2019 +C15133,1R43HL158291-01,Highly Selective Pathogen Inactivators For Treatment of Convalescent Transfusion Plasma,"ABSTRACT Presently, convalescent plasma (CP) transfusion is being developed as a therapy for COVID-19 patients and as a prophylactic for high risk individuals. In addition, treatment with plasma or neutralizing antibody preparations from convalescent patients could be the only treatment for emerging infectious diseases, for which no other treatments may be available. At the same time, CP transfusion exposes the recipient to the risk of transfusion transmitted diseases (TTD), a risk which is additionally exacerbated by the compromised immune conditions of the critically ill patients. The limited number of current TTD blood tests does not provide for full protection, restrict the critically limited donor's pool and may not be available in some areas. Pathogen Inactivation can provide the solution. Unfortunately, the currently utilized treatments for pathogen reduction in plasma (solvent-detergent, pasteurization of dry heat, UV or gamma irradiations) are non-selective and can compromise the quality of plasma's neutralizing antibodies or other protective protein factors. We at ZATA Pharmaceuticals have developed a new class of pathogen inactivators (ZPI) based on the natural polyamines scaffold, which are truly selective in inactivating pathogens genomic molecules while sparing plasma proteins. Our preliminary results show that ZPI have high reactivity toward nucleic acids and do not modify model proteins (Cyt-C, RSV fusion protein) and animal sera growth factors. Using them, we inactivated different types of pathogens (G+ and G- bacteria, mycoplasma, fungi, protozoa) and high titer preparations of enveloped or non-enveloped viruses. Currently we are developing ZPI for pathogens reduction in transfusion red blood cells, research funded by NIH SBIR grant (R44 HL145783). In this application we propose to adapt the new pathogen inactivation process for treatment of convalescent plasma (CP) by: (1) using 6 virus species in human plasma to select the optimal ZPI and conditions for pathogen inactivation in human plasma; (2) using already developed analytical methods to establish conditions for complete neutralization and/or removal of the residual inactivator from the treated plasma; (3) using specific antibodies against 4 virus species to demonstrate by ELISA that the virus inactivation treatment has no effect on the binding of the antibodies to their targets; (4) using neutralizing antibodies against SARS-CoV-2 S protein to demonstrate preservation of the virus neutralizing properties of the antibodies after plasma treatment; (5) using repeated autologous infusion of treated plasma to establish its in vivo the safety in the rabbit models. After accomplishment of those initial goals we will apply for funding, including SBIR funding to complete, in collaboration with New York Blood Center, its pre-clinical evaluation and to initiate phase I human trials, or alternatively, will license the treatment procedure for completion of its development and marketing. Ultimately, this proposal will lead to a safe and high quality convalescent human plasma for treatment or prophylactics of COVID19 or other deadly diseases for which no other effective treatment is currently available.",2021,2022,N/A,717598,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15134,1R01AI160953-01,Fusion inhibitors that block host-to-host transmission of SARS-CoV-2,"Coronaviruses (CoVs) can cause life-threatening diseases. The recently emerging coronavirus-related illness was named coronavirus disease 2019 (abbreviated ""COVID-19"") by the World Health Organization. COVID-19 is caused by SARS-CoV-2. Like its predecessors SARS-CoV and MERS-CoV, SARS-CoV-2 (S-CoV-2) is a betacoronavirus that is thought to have originated in bats. Originally its spread was animal-to-human, but human-to-human transmission is now widespread. No vaccines and treatments for COVID-19 are available, and these are urgently needed to address the outbreak as well as inevitable ongoing infection. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viruses. In this proposal, we will apply the results of our fundamental research to the development of novel peptide inhibitors of SARS- CoV-2 entry. We have designed lipid-conjugated fusion-inhibitory peptides that efficiently inhibit coronavirus infection in in vitro, ex vivo, and in vivo. We propose to synthesize and evaluate novel lipidated peptides that have enhanced efficacy. These inhibitors will be evaluated for antiviral activity against live SARS-CoV-2 virus. Promising candidates will be tested in transmission experiments in a ferret model. This application will determine whether our approach to entry inhibition of SARS-CoV-2 prevents infection in vivo. 1. To optimize antiviral potency of HRC-lipopeptide fusion inhibitors. 2. To pre-clinically evaluate HRC-lipopeptide fusion inhibitors biodistribution, toxicity and protection against SARS-CoV-2 infection or transmission in vivo.",2021,2026,N/A,750151,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15135,1R01AI160167-01A1,Mechanisms and pathogenicity of SARS-CoV-2-induced neutrophil extracellular traps,"Project Summary/Abstract The acute respiratory distress syndrome (ARDS) was first formally described in 1967, but it has likely been the predominant cause of death in pandemic viral infections for centuries. Now, the world is at grips with a new pandemic from SARS-CoV-2, or COVID-19, which has infected over 100 million people worldwide resulting in >2 million deaths. Central to the immunopathogenesis of ARDS is the role of neutrophils and neutrophil activation, including the release of neutrophil chromatin into the extracellular space in a process termed neutrophil extracellular traps, or NETs. Originally described as a form of host defense to inactivate pathogens, NETs have emerged as a potentially maladaptive response to infections, producing substantial bystander injury to tissues and serving as a nidus for coagulation. We have shown that NETs are produced in response to both sterile and pathogen-induced acute lung injury (including Influenza A), and when neutralized, lung injury is reduced without compromising microbial containment. We have also shown that NETs are increased in the plasma of patients with ARDS and associate with more severe ARDS and ARDS mortality. Emerging reports indicate that NETs are also present in the blood and lungs of COVID-19 patients. We are now positioned to rapidly test the role of NETs in response to SARS-CoV-2 in this application, and to develop novel approaches to neutralize NETs for therapeutic purposes. In Aim 1, we will challenge neutrophils with SARS-CoV-2 virus or spike protein to determine the production of NETs and NET-induction molecular pathways. We hypothesize that secreted neutrophil proteases and NETs themselves will cleave spike protein to prime for enhanced viral pathogenesis. We will also embark on unbiased studies of neutrophil proteins using mass spectrometry to determine novel pathways of neutrophil activation resulting from SARS-CoV-2, including from neutrophils isolated from COVID-19 patients. In Aim 2, we will turn our attention to a mouse model of COVID-19 in which mouse strains expressing human ACE2 will be challenged with SARS-CoV-2 and lung injury, NETs, and systemic effects measured. We hypothesize that NETs will be produced and predominantly localize to the alveolar spaces. We will use mice with gain and loss of function mutations in NET pathways (PAD4-/-, DNase1- /-, DNase1L3-/-) to test for their pathogenicity in this model. In these studies, we will also test a novel DNase to neutralize NETs into non-toxic mononucleosomes, which could be rapidly deployed to COVID-19 patients. Finally, we will test for the role of NET-associated platelet activation, complement activation, and coagulation responses, and therapeutic strategies to mitigate these systemic effects. In summary, these studies will establish new knowledge on neutrophil activation and the definitive role of NETs in COVID-19 and identify therapeutic approaches to target NETs in SARS-CoV-2-induced ARDS.",2021,2026,N/A,623280,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +C15136,1R03AI163907-01,Rapid SARS-CoV-2 Detection Using Amplicon Templated Reporter Enzyme Assembly,"ABSTRACT We are proposing to pilot test a new enzyme biosensor technology for the purpose of enhancing isothermal RNA amplification assays for SARS-CoV-2. Our overarching goal is to validate this technology, called DETECT, as biomolecular tool to increase the sensitivity, specificity, and speed of SARS-CoV-2 testing. DETECT is based on a modified split luciferase enzyme complementation assay. Instead of the standard bait and prey fused protein constructs, we connect two non-interacting luciferase fragments to SARS-CoV-2 oligonucleotide probes. Conjugation of the luciferase fragments to the oligonucleotides uses a chemi-enzymatic method developed in the investigator's lab. The oligonucleotides are designed to anneal to adjacent segments in a unique SARS-CoV-2 amplicon. With samples containing the amplicon, the split luciferase fragments are brought together through base pairing of their attached oligonucleotides with the SARS-CoV-2 amplicon. Molecular assembly reconstitutes functional luciferase from the two fragments, enabling robust light output. In preliminary experiments, we validate the central and novel concept of DETECT: protein fragment complementation via nucleic acid base pairing. In controls where base pairing of the oligonucleotides is blocked, either by exonuclease pretreatment or by competitor oligonucleotide, we observe luminescence readings on par with buffer only samples. By contrast, in experimental samples where oligonucleotide base pairing is supported, we observe luciferase signal that is increased 100- fold over background. These preliminary experiments were carried out with the split luciferase- oligonucleotide conjugates at 25 nM. Over the course of this 2-year project, we propose to evaluate the DETECT system quantitatively for specificity, sensitivity and speed, thereby assessing the clinical potential of this biosensor technology. Although our objective here is diagnosing SARS-CoV-2 infection, the DETECT system is easily re-programmed by changing the oligonucleotide probe sequences. Thus DETECT holds promise as a new and innovative diagnostic platform.",2021,2023,N/A,78500,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15137,3UM1AI148689-02S7,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site: DMID 21-0012 Mix and Match,"Summary/Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease of 2019 (COVID-19) which was designated as a pandemic respiratory illness (WHO - 2020), has infected over 172 million people worldwide and resulted in over 3.7 million deaths, including > 596,000 in the United States (June 3, 2021, WHO; www.who.int). Multiple Phase 3 efficacy trials of SARS-CoV-2 vaccine constructs are underway or in long-term follow-up in the U.S, and these studies have supported 3 Emergency Use Authorizations (EUAs) for COVID vaccines. However, logistical and manufacturing obstacles are limiting the number of vaccines available at any one time. Further, the emergence of variant strains has raised concerns about the breadth of immunity and protection achieved by the current vaccines. WHO SAGE and CDC ACIP have identified the safety and immunogenicity of mixed schedules as a critical and immediate research priority to inform policy on the use of mixed schedules. Knowledge of the safety, tolerability, and immunogenicity of a delayed boost vaccine incorporating a heterologous platform or variant spike lineage administered following EUA prime dosing regimens may greatly stretch the ability to immunize against SARS-CoV-2 at a population level, induce immunity to variant circulating strains and improve upon the breadth and durability of protection. The heterologous boost strategy will also provide an opportunity to thoroughly evaluate innate, cellular, and humoral immune responses elicited from the multiple prime boost combinations using very similar immunogens, utilizing mRNA, adenovirus- vectored, and protein- based platforms. As new immunogens are manufactured to closely match emerging variants, these foundational data will be key to the evaluation of future variant and heterologous prime- boost strategies. This phase 1/2 clinical trial will evaluate the safety and immunogenicity of different heterologous delayed doses (boosts) in those who received an EUA vaccine (either prior to participation in this trial, or as part of this trial).",2021,2025,N/A,1121472,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2021 +C15138,1R41AI157347-01A1,COVID-19: High Efficiency SARS-CoV-2 Virus Aerosol Sampling and Sensing,"As the current COVID-19 pandemic has demonstrated, aerosolized pathogens such as SARS-CoV-2 can spread explosively if not quickly detected. Early detection of these airborne pathogens can help control out- breaks, particularly within vulnerable populations in densely populated spaces including assisted living facili- ties, places of worship, military installations, hospitals, and prisons. To date, most studies of aerosolized SARS-CoV-2 use filter collection followed by laboratory analysis of viral RNA. While this gives a general indica- tion of viral RNA levels in an environment, filters collect both infectious and non-infectious viruses and damage them through mechanical stress and desiccation, making it difficult to determine the infective fraction of the col- lected viruses. Further, current filter analysis methods require time-consuming nucleic acid extraction and am- plification techniques not suitable to rapid, point-of-care monitoring. Therefore, there is an urgent need for in- struments that can detect intact viruses at the point-of-care. We propose to develop a sensitive, direct reading, bioaerosol detection platform that can quantify specific air- borne pathogens at the point of collection. Furthermore, if a positive result is identified, the sample can be taken to a central laboratory for additional molecular analysis and infectivity testing. This device will integrate the bioaerosol collection technology developed at Aerosol Devices Inc. (ADev) with virus detection technology from Colorado State University (CSU). Using gentle condensation-growth capture that mimics the human lung, the ADev sampler will be the front-end of the platform, concentrating intact, viable virus particles into a small liquid volume. With >90% collection efficiency for particle sizes <10 nm up to 10 µm, ADev samplers uniformly collect all inhalable SARS-CoV-2 particles whether originating from cough droplets (>5 µm), smaller particles exhaled during breathing or talking (<5 µm), or shed as individual virus particles (~120 nm). CSU Professors Henry, Dandy, and Geiss are developing innovative, inexpensive electrochemical biosensors to rapidly detect intact viruses in liquid samples. By synergizing these robust sensors with the ADev aerosol sampler, we will produce a system that can detect and quantify ultra-low concentrations of viral pathogens in near real-time. In this phase I STTR project, we will adapt our commercial aerosol-into-liquid collector to incorporate CSU's biosensors. Specific aims for the ADev sampler include extending sampling time to 24 h to enhance limits of detection, increasing volumetric sampling rate to improve temporal resolution, selecting materials compatible with VHP decontamination and optimizing the system to reduce size, weight, power consumption and cost. Specific aims for the biosensor include modifying electrodes to detect SARS-CoV-2 particles with high sensitiv- ity and selectivity, adapting our current electrode configuration to work with the ADev sampling vial, and testing the system with infectious SARS-CoV-2 in our BSL-3 laboratory. Our immediate focus is SARS-CoV-2, but this technology can be adapted in Phase II to detect any airborne pathogen (e.g., Influenza, B. anthracis, etc.).",2021,2022,N/A,262802,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Environmental stability of pathogen,2021 +C15139,3UM1AI068635-15S4,CoVPN 5001 A prospective study of acute immune responses to SARS-CoV-2 infection SDMC,"This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of a natural history trial for acute SARS-CoV-2 infection in hospitalized and non-hospitalized individuals: ""A Prospective Study of Acute Immune Responses to SARS-CoV-2 Infection."" With the onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in the field on the contribution of innate and adaptive immune functions in modifying COVID-19 disease and in clearing viral infection and in the ability of vaccines to prevent or modify COVID-19 disease in SARS-CoV-2 infected individuals. Addressing this gap, the National Institute of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician scientists at 64 United States (US) and 55 international clinical trial sites in 15 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. We believe the CoVPN is well placed to study the natural history gaps and rapidly deploy this information in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study we propose initiating an observational cohort study of approximately 800 acutely infected persons recruited at 17 United States (US) and 43 international clinical trial sites over an 8 month period. Adults 18 years and older with RT-PCR positive SARS-CoV-2 test results will be enrolled competitively across trial sites until the full cohort is reached. Participants will follow up for 6 clinic visits over a 28 day period and receive a final remote contact one month after the last visit. Participants who experience clinical decompensation will be referred for hospital evaluation. Specific aims of the study are to generate standardized datasets characterizing the SARS-CoV-2 viral kinetics and the quality, magnitude, and kinetics of humoral, innate and cellular immune responses to SARS-CoV-2 infection in asymptomatic and acutely symptomatic participants (in both hospitalized and non-hospitalized individuals) from a diversity of geographic and genetic backgrounds. This natural history study will tell us much about the adaptive immune responses in persons who are acutely infected from SARS-CoV-2 and will shed light on the role the immune system plays in successfully clearance of infection. It will improve our understanding of the dynamics and duration of responses, as well as the epitope specificity and other defining signatures, and will inform rational design and testing of preventive and therapeutic vaccines and monoclonal antibodies. Lastly, this study will prepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.",2021,2021,N/A,673501,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15140,3P51OD011092-62S3,Novel Therapy for SARS-CoV-2 Virus Infection and Pathogenesis by Aerosol Delivery of Monoclonal Antibodies,"PROJECT SUMMARY The Oregon National Primate Research Center (ONPRC) is one of seven National Primate Research Centers (NPRCs) established by Congress in the 1960s. The NPRCs are sponsored by the NIH Office of the Director, and serve the nation's biomedical research needs in a unique and essential fashion through cost-effective provision of NHPs and related scientific expertise, specialized facilities, and equipment to federally funded studies of NHPs that comprise a vital translational link between basic research and human applications. The mission of the ONPRC is to improve human health and the quality of life through NHP research programs that advance our knowledge of the causes of human diseases and that develop effective preventions, treatments, and cures. The Oregon National Primate Research Center (ONPRC) P51 Core Grant (P51-OD011092) supports a colony of approximately 4900 breeding and research nonhuman primates (NHPs), including rhesus macaques of Indian origin, Japanese macaques, cynomolgus macaques, Hamadrayas and olive baboons, and a small number of squirrel monkeys. Rhesus and Japanese macaques are bred at the Center. Other species are imported from domestic sources to fulfill project specific research needs. In this supplement proposal to the parent grant, we will test the hypotheses that: 1) When given prior to challenge, inhaled, aerosolized neutralizing monoclonal antibodies can prevent or mitigate SARS-CoV-2 infection in rhesus macaques; and 2) Inhaled neutralizing monoclonals can reduce viremia and prevent pathogenesis when given after challenge. To test these hypotheses, we will test a cocktail of human mAbs with potent and broad SARS-CoV2-neutralizing activity for their effectiveness in pre-exposure protection and/or limitation of viral shedding following aerosolization and administration by inhalation prior to intranasal/intratracheal challenge with SARS-CoV-2. Animals will be followed for virological and immunological outcomes and pathology using standard protocols developed by the Coronavirus Vaccines and Therapy Evaluation Network. At necropsy, tissues will be harvested and processed for virus quantification and histology. For post-exposure studies, macaques will be infected with SARS-CoV-2, and treated one day later with the same cocktail of human SARS-CoV-2 mAbs, comparing aerosol and intravenous delivery at various doses. These proof-of-principle experiments will pave the way for post-exposure aerosol treatments with potent antibodies and nanobodies toward the goal of reducing COVID-19 disease. Our findings will expand the utility of the nonhuman primate model for SARS-CoV-2 and will support the discovery of novel therapeutics for COVID-19, thereby fulfilling the primary purpose of the P51 grant.",2021,2024,N/A,499631,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +C15141,3P20GM130418-02S1,Community-engaged research to promote SARS-CoV-2 vaccine uptake in Montana's American Indian and rural communities,"Project Summary/Abstract Racial and ethnic minorities, and other medically underserved groups, including rural adults, have been particularly hard hit by SARS-CoV-2, the virus that causes COVID-19 disease. In the United States, the COVID-19 case fatality rate is 25% higher in rural versus urban areas. In Montana, a large, rural Western state, American Indians (AIs) are 7% of the population but have accounted for 18% of COVID-19 deaths. As of April 2021, SARS-CoV-2 vaccines are widely available to eligible adults throughout the state; however, only 33% of Montana adults are fully vaccinated, and demand for the vaccine is waning. As we transition from initial implementation to long-term delivery of these vaccines, primary care providers (PCPs) will be responsible for recommending booster doses, offering the vaccine to newly eligible populations such as children, and convincing previously unvaccinated people to get the vaccine. In this Center for Population Health Research (CPHR) community-engaged research project, our long-term goal is to identify culturally specific and community competent health systems- and provider-level strategies for increasing SARS-CoV-2 vaccine acceptance in AI and rural populations. To achieve this goal, we will collaborate with All Nations Health Center in Missoula, MT to conduct qualitative interviews with vaccinated and unvaccinated AI and rural adults to identify causes of SARS-CoV-2 vaccine confidence and hesitancy (Aim 1). Using qualitative content analyses, we will also identify trusted sources of vaccine information and participant-generated ideas for promoting vaccine confidence and uptake in these communities. We will also conduct a statewide survey of PCPs to determine readiness for addressing SARS-CoV-2 vaccine hesitancy (Aim 2). The survey will include a module regarding knowledge, attitudes, and beliefs about the SARS-CoV-2 vaccines, including questions about confidence in addressing patients' vaccine questions and concerns, as well as questions regarding perceptions of future vaccine authorization for children. Due to our collaborative history with the Montana Department of Public Health and Human Services Immunization Section and health systems throughout the state, we are positioned to facilitate the rapid translation of this study's results into immunization services delivery practice. Furthermore, we anticipate that findings from this study will be generalizable to other states with similar populations, and our team will serve as a key contributor to the national conversation on effective strategies to address SARS-CoV-2 vaccine hesitancy among vulnerable AI and rural populations.",2021,2025,N/A,165790,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2020 +C15142,1I01BX005507-01,COVID19: Respiratory SARS-CoV-2 seroprevalence and the association of humoral immune responses with clinical outcomes in veterans and employees in the Cleveland VA Medical Center,"The global pandemic of SARS-CoV-2 is placing urgent demands on health care workers and researchers. Between April 3rd and May 1st global cases of COVID19 nearly tripled from approximately 1 million to over 3 million. With the possibility of a reemergence of SARS-CoV-2 in the fall, rapid specific antibody assays are essential. This application proposes to investigate the humoral immune responses to SARS-CoV-2 in veterans and employees at the Cleveland VA Medical Center. The proposal has three aims. Aim 1) To develop rapid, high throughput assays to measure total and functional antibodies to SARS-CoV-2 proteins in COVID19 infected individuals. In aim 1, we will establish a magnet bead-based assay that can detect antibody (Ab) responses to up to 50 different epitopes of SARS-CoV-2 in one serum sample. This assay will also be able to detect Abs that interfere with the binding of the receptor binding domain (RBD) of the spike protein of SARS- CoV-2 to its receptor, ACE2. Antibodies that can block binding between the RBD and ACE2 on lung epithelial cells will prevent viral entry and will likely be neutralizing. Aim 2) To determine if robust humoral immunity and higher neutralizing Ab titers protect VA health care employees from clinical COVID19 compared to their colleagues with low or no SAR2-CoV-2 specific antibodies. In aim 2 we will use a rapid antibody test to screen Cleveland VA health care employees at high-risk for infection with COVID19 (first responders, emergency department staff, intensive care unit staff, COVID19 ward staff). We will ask for a serum sample from those that are Ab positive for COVID19 to examine the SARS-CoV-2 Ab response in more depth. We will examine general Ab titers, neutralizing Ab titers, and antibody isotypes. If there is a resurgence of COVID19 in the fall, we will determine if those health care employees with a robust humoral response are better protected from re- infection than those employees who had a weak or no Ab response. Aim 3) To examine the association of COVID19-induced lymphopenia with the ability to generate a humoral immune response. Older age, SARS- CoV-1 and SARS-COV-2 infection are all associated with a decrease of white blood cells or lymphopenia. In aim 3 we will examine the effect of lymphopenia on the development of the humoral Ab response to COVID19. We expect that those individuals with severe lymphopenia will have few T follicular helper cells in their lymph nodes and this will lead to poor Ab affinity maturation, isotype switching, and B cell memory development. In summary, results from this project will provide a rapid SARS-CoV-2 specific serum assay able to detect neutralizing Ab that can be used to screen VA healthcare workers for exposure to SARS-CoV-2. We will investigate the humoral antibody responses of high-risk health care employees that were infected with COVID19 and try to determine what constitutes protection from re-infection if there is a resurgence of COVID19 in the fall. Lastly, we will gain an understanding of the B cell affinity maturation, isotype switching and generation of B cell memory and neutralizing Ab titers and determine how lymphopenia may play a role in the dysfunction of humoral immunity to COVID19. This knowledge will aid in development of better treatment and future vaccines.",2021,2023,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Military Personnel | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2021 +C15143,1R21AI158175-01,Integrated Analysis of SARS-CoV-2 Vaccine Responses During Aging,"Production of high-affinity class-switched antibodies is essential for elimination of viruses and immunity elicited by vaccination. Vaccination has led to the eradication of some diseases, but in some settings do not provide sufficient protection, such as in elderly or immunocompromised individuals. Antibody responses are controlled by humoral immunoregulatory pathways, including inhibition by Tfr cells, which suppress B cell effector functions. Aged-related defects in vaccine responses are partially due to enhanced humoral immunoregulation by Tfr cells. Since the COVID19 pandemic disproportionally affects at-risk populations such as the elderly, new vaccine strategies need to be developed to enhance protection for this group. However, a fundamental understanding of how humoral immunoregulation associated with aging alters SARS-CoV-2 vaccine responses is lacking. We hypothesize that augmented humoral immunoregulation by Tfr cells during aging alters SARS-CoV-2 vaccine responses, and that limiting Tfr cells can enhance vaccine efficacy. We also hypothesize that limiting humoral immunoregulation results in production of new and unique therapeutic antibodies. To test these hypotheses, we will use a novel systems-based approach to integrate, on a per cell basis, SARS-CoV-2 antibody specificity, breadth, viral neutralization potential, and antibody sequence/clonality. We will use novel Tfr-deleter mice to assess how humoral immunoregulation alters these responses. Our aims are to 1) determine how augmented humoral immunoregulation in aging alters clonal selection of neutralizing antibodies during SARS-CoV-2 vaccination, and 2) determine how eliminating humoral immunoregulation enhances clonal selection of neutralizing antibodies. Our goals are to determine, in detail, how humoral immunoregulation alters antibody selection to control effector antibody responses after vaccination.",2021,2023,N/A,255860,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Characterisation of vaccine-induced immunity,2021 +C15144,1R01AI158373-01A1,Inhalation Therapy Platform for Coronavirus Infection Treatment,"PROJECT SUMMARY/ABSTRACT The newly emerged SARS-CoV-2 coronavirus has demonstrated the deadly threat of pulmonary pathogens in an exposure-naïve world with no existing vaccines or therapeutics at the ready. The development of effective vaccines has provided key prophylactic products, but therapeutics remain important due to slow and incomplete world coverage, along with emergence of resistance variants. There is especially a need for polytherapy platforms that can be deployed in formats amenable to global settings, and need for platforms that can be rapidly developed against future pulmonary threats. This project aims to develop a versatile inhalable therapeutic platform against COVID-19 disease and future coronaviruses. It is designed for nebulizer and distributable inhalation devices to maximize drug activity in the lung. The polymeric prodrug platform has recently shown strong potentiating activity against highly lethal and antimicrobial-resistant bacterial lung infections. These ""drugamer"" therapeutics improve the activity of pulmonary drugs by targeting them to specific cell reservoirs in the lung with high and extended dosing profiles. The inhalable platform could be used by infected patients before hospitalization, to reduce administrations by patients in crowded hospitals, and contribute a key distributable therapeutic and prophylactic modality that is needed to protect caregivers and disadvantaged populations. The proposal is structured around 4 specific aims: (1) Develop remdesivir and baracitinib as first drugamer candidates that exploit the lung macrophage as a reservoir to achieve extended dosing, as well as targeted designs against lung epithelium viral reservoirs. Remdesivir and baracitinib prodrug monomers will be developed with corresponding drugamer designs with mannose and peptide targeting ligands for the alveolar macrophage and epithelial compartments, respectively; (2) Characterize and optimize the drugamer candidates by criteria of how they load drugs into the lung macrophage and epithelial cells with extended dosing times. This will lead to better understanding of how to optimize targeting strategies in the lung for future antiviral development. The mechanisms will be studied by using quantitative LC-MS pharmacokinetics characterization and safety characterization using lung inflammatory response assessments; (3) Assess and optimize drugamer activity against SARS-CoV-2 using the hACE2 mouse model. Viral load and survival studies will be used to characterize and develop optimized drugamer and drugamer combinations that could in the future be carried forward into preclinical development. Compared to current formulation approaches, the drugamers exhibit higher drug loading, the ability to co-formulate widely varying drugs for polytherapy, and individually tailorable drug PK profiles that minimize burst release. The modularity of the platform, together with scaled and rapid manufacturing response attributes, will allow diverse incorporation of other drugs as combinations. These favorable platform attributes motivate this project to develop a new repertoire of current and future coronavirus therapeutic products.",2021,2026,N/A,634365,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Pre-clinical studies | Prophylactic use of treatments",2021 +C15145,3R01HD100022-03S1,Helping Us Grow Stronger (HUGS/Abrazos): COVID-19 in pregnancy and reducing toxic stress in mother-infant dyads,"PROJECT SUMMARY Pregnancy and early childhood mark a unique period when two lives can be permanently impacted by the presence of maternal stressors such as economic instability, poor mental health, and social inequities, all of which have been amplified by the COVID-19 pandemic. The COVID pandemic has also collided with the epidemics of racism and maternal mortality plaguing the United States, to disproportionately impact already- marginalized Black and Latinx pregnant individuals in the greater Boston area. In the absence of protective buffers, prolonged exposure to excessive adversity (""toxic stress"") can lead to poor health outcomes for both mothers and infants. Effective interventions to improve maternal mental health and mitigate social determinants of health in individuals with COVID-19 in pregnancy are therefore urgently needed. Helping Us Grow Stronger (HUGS/Abrazos) is a community-based program, designed and launched during the COVID pandemic. HUGS/Abrazos combines emergency relief, patient navigation, and direct behavioral health support to foster resilience and mitigate the negative impacts of COVID-related toxic stress on pregnant and postpartum women and their families. Participants enrolled in Massachusetts General Hospital's COVID-19 Pregnancy Biorepository will be referred to the HUGS/Abrazos program if they test positive for SARS-CoV-2. Using validated survey instruments, we will assess the extent to which the program improves maternal stress, anxiety, depression, quality of life, food insecurity, and experiences of racism and discrimination in this high-risk pregnant population. We will also assess the impact of maternal COVID-19-associated inflammation on behavioral health outcomes using cytokine analysis of banked serum samples from the participants. This urgent competitive revision of the R01 ""Fetal Brain-Placental Immune Activation in Maternal Obesity"" is aligned with the R01's long-term translational goals: to understand how in utero exposure to maternal inflammation and immune activation impacts fetal programming, in order to create targeted interventions that can improve short- and long-term maternal and child health outcomes in the face of maternal exposures. This work will generate key knowledge about the efficacy of a novel community-based intervention to reduce the adverse impact of maternal SARS-CoV-2 infection on the mother-infant dyad, and improve transgenerational outcomes.",2021,2022,N/A,419987,Human Populations,Black | Other,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2019 +C15146,1R01AI158410-01A1,Natural Killer cells and the Immunogenetics of COVID-19,"Summary To ensure a successful and sustained response to the COVID-19 crisis it becomes imperative that the functional implications of the considerable genotypic and phenotypic variation in natural human immunity are understood. Natural killer (NK) cells have major roles in controlling the innate and adaptive immune response to viral infections, including herpesviruses, HIV-1, influenza, and SARS. NK cells comprise a significant part of the front-line defense against pathogen invasions and are present at large numbers in lung tissues. NK cell effector functions, including cytokine release and cytotoxicity, are modulated by interactions of killer cell immunoglobulin-like receptors (KIR) with class I human leukocyte antigens (HLA) expressed on tissue cells. Across individuals, there is enormous diversity in the number and nature of viable receptor and ligand pairs and within individuals, there is a multitude of NK cell subsets distinguished by their receptors. Previous studies of epidemic diseases have identified clear relationships between this diversity and susceptibility, resistance or control of infection. Likely reflecting exposure throughout human history to multiple, diverse and geographically discrete pathogens, the HLA and KIR genes are highly variable across individuals and population groups. These genetic variations have direct impact on NK cell functions and the response to infection. Allotype-dependent interactions of KIR with HLA inform, modulate and diversify NK cells in their role of identifying and eliminating virus-infected tissue cells. Consideration of the full extent of this variation across human populations is thus critical to understanding, diagnosing and treating SARS-CoV-2 infection, and for developing and testing vaccines. The overarching hypothesis that we will investigate is that genetic variation of HLA and KIR can determine the course of immunity following SARS-CoV-2 infection, leading to severe COVID-19 in some individuals. The first Aim of our study will examine a large multi-ethnic cohort of 11,500 SARS-CoV-2 infected patients, to determine the association of HLA and KIR genetic diversity with severity of disease. The cohorts are drawn from the countries hardest hit by the pandemic, including Brazil, Italy, Spain, UK and the USA. NK cells recognize infected cells through loss of ligands for inhibitory receptors or gain of ligands for activating receptors. Many viruses are known to exploit any or all of these mechanisms to evade immune detection. The second Aim will examine the role of SARS-CoV-2 derived proteins in evading NK cell driven immune responses, and how this varies across all known HLA and KIR allotype interactions. NK cells can be activated by antibodies that are bound to virus segments on the surface of infected cells, and we have shown this activity is also dependent on HLA and KIR diversity. The final Aim will therefore examine the role of antibody-dependent elimination of SARS-CoV-2 infected cells, and the impact of KIR and HLA polymorphism on this response. Validating our approach, our preliminary findings already identified one potential therapeutic target. Our findings will thus have immediate consequence for identifying individuals most at risk for developing severe COVID-19, for developing both universal and personalized treatment, and to aid in vaccine design.",2021,2025,N/A,742765,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas | Europe,,,,,Brazil | Italy | Spain | United Kingdom | United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity,2021 +C15147,1R21AI160334-01,Protective and Pathogenic T Cells Responding to SARS-CoV-2 in Health and Disease,"SUMMARY Understanding the adaptive response to SARS-CoV-2 is critical to halting the devastation wreaked by the COVID-19 pandemic, by identifying new drug targets and informing the rational design of vaccines. Common coronaviruses and human rhinovirus (RV) both cause common cold, and multiple strains of each exist that have varying degrees of sequence identity. All humans, and adults in particular, possess antigen-experienced immune cells by virtue of frequent viral infections. Our work using experimental infections with RV in man has provided unprecedented insight into adaptive immunity to this relatively benign, but troublesome, virus. Seminal findings include a pivotal role for the rapid mobilization of cross-reactive memory T helper 1 (Th1) cells and T-bet+ B cells in controlling RV infection. Th1 cells are critical to anti-viral responses by aiding in viral clearance through secretion of IFN-γ, and providing help to B cells for the production of neutralizing antibodies. Notably, expansion of circulating RV-specific Th1 cells is limited to those infected patients who develop serum neutralizing antibodies, whereas this feature is lacking in those who are infected but fail to mount an antibody response. Nonetheless, there is also evidence of a pathogenic role for virus-specific Th1 cells in patients with asthma who are at risk of adverse sequelae, based on enhanced and persistent responses. We posit that a similar scenario underlies the ""cytokine storm"" and rapid decline in patients with severe COVID-19 and those who are at risk, thereby reflecting the double-edged sword of Th1 cells in anti-viral immunity. The technological tools and analytical pipelines developed to study cross-strain immunity to RV infections, coupled with access to COVID-19 patients and those at risk, allow us to pivot quickly to analyze T cell responses to SARS-CoV-2. Powerful single-cell analytical tools for interrogating large cell numbers will be used to test the theory that cross-reactive T cells respond rapidly to SARS-CoV-2, and their numbers and functional attributes determine disease status in healthy individuals and at-risk patients. Based on our expertise, we are uniquely poised to map CD4+ T cell epitopes across the SARS-CoV-2 proteome. These data will be used to generate MHCII/peptide tetramers to detect and phenotype cross-reactive SARS-CoV-2-specific memory CD4+ T cells that pre-exist in uninfected adults and persist in recovered COVID-19 patients. This will establish proof-of- concept for priming of T cells for rapid response by previous exposures to related coronavirus strains (Aim 1). Next, novel computational tools and tetramers will be used to identify hallmarks of overactive virus-specific T cells in hospitalized COVID-19 patients in the acute phase, and to assess immune paralysis and antibody deficiencies in those who develop respiratory failure (Aim 2). Finally, we will confirm in vivo expansion of virus- specific pathogenic Th1 cells in uninfected asthmatics with severe disease, and boosting of their function by pro-inflammatory cues present in the lower airways (Aim 3). Study outcomes will yield new insight into T cell mechanisms of viral pathogenesis, and aid in vaccine design and monitoring for COVID-19.",2021,2023,N/A,242250,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15148,1R01DK130381-01,Understanding the interplay between local viral infection and local inflammation in COVID-19 kidney injury,"PROJECT ABSTRACT Acute kidney injury (AKI) is a common complication of Coronavirus disease 19 (COVID-19), affecting more than a third of patients hospitalized with COVID-19 and up to 90% of those requiring mechanical ventilation. Possible contributors to AKI in patients with COVID-19 include systemic inflammation and cytokine release, hemodynamic compromise, and intravascular coagulation. Additionally, several reports have suggested the presence of SARS- CoV-2 viral particles or viral RNA in the kidney tissue of patients who died from COVID-19, suggesting a potential role for local viral infection in the kidney. SARS-CoV-2 is known to infect and replicate in kidney cell lines, and in preliminary data we show that viral RNA can be amplified from the urine of patients with severe COVID-19 and AKI, even after the virus has been cleared in the respiratory tract. Genetic analysis of those viral RNA in urine demonstrated a predominant pattern of deletions and mutations at the furin-cleavage site of SARS-CoV-2 that have not been observed in over 180,000 SARS-CoV-2 genome sequences from respiratory tract samples deposited in the publicly available database GISAID. However, those mutations have been reported to occur after virus passaging in the African green monkey kidney cell line Vero-E6, raising the possibility that those mutations might be positively selected following virus replication in kidney cells. The primary goal of this application is to understand the interplay between local viral infection and local inflammation in COVID-19-related kidney injury by leveraging our expertise in the study of HIV-related kidney disease. Our specific objectives are 1) to isolate and genetically characterize SARS-CoV-2 from urine samples of COVID-19 patients with mild, moderate or severe disease, 2) to explore the relationship between SARS-CoV- 2 infection of renal cells and urine inflammatory markers; and 3) to determine the impact of genetic mutations on viral fitness. Understanding the role of direct viral infection of renal epithelial cells is key to the design of interventions to prevent and treat AKI in COVID-19. Further characterization of the viral mutants isolated from urine may provide insight into viral pathogenesis and would inform the design of antiviral and adjunctive therapies for SARS-CoV-2 infection.",2021,2024,N/A,402500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2021 +C15149,3R01DA051202-02S1,Immune Dysfunction in HIV + Opiod Users,"This Competitive Revision application for 2019 Novel Coronavirus research is related to the current grant Immune Dysfunction in HIV+ Opioid Users (DA051202) which is investigating influenza vaccine responses in people with HIV (PWH) who have opioid use disorder (OUD). The premise for the funded grant is that HIV infection impairs immunity with evidence of persisting immune perturbations even after durable virologic control. Opioids are immunosuppressive and abuse through prescription or injection can be damaging to the immune system and prove to be specially harmful in PWH. Our central hypothesis in the parent grant is that chronic opioid use by PWH (HIV+OP+) blunts the immune response and impairs the generation of influenza vaccine induced immune response. Our plan is to investigate participants in 4 groups (HIV+OP+, HIV-OP+, HIV+OP- and HIV-OP-) before and after influenza vaccine administered as a clinical trial. The project funding started in the midst of the COVID-19 pandemic that has resulted in global morbidity and mortality. The clinical course of SARS-CoV-2 infection is highly variable, ranging from asymptomatic to severe disease resulting in full recovery, death, or persistent symptoms described as PASC (post acute sequalae of COVID- 19) which can affect one or more organs such as the brain, heart, lung, gut, kidneys, or musculosleletal system. The immune response generated by SARs COV-2 is dynamic, involves innate and adaptive immunity and evolves with the stage of the disease. Antibodies to the spike protein's receptor binding domain corelate with neutralizing activity and form the basis of judging effectiveness of current vaccines as well as monoclonal Ab therapy. Duration of Ab in the host following SARS CoV-2 infection or vaccination is unknown and there are gaps in our knowledge about the role of T cells in Ab persistence or emergence of viral variants. It is also unknown if COVID-19 causes detrimental effects on immunity and if this effect varies depending on the host's immune competence, with the greatest impact in an immunocompromised host. These issues are relevant for the HIV+OP+ population and need to be investigated. While Ab formation to SARS CoV 2 is dependent upon infection or vaccination, T cell memory for SARS CoV2 has been shown to pre-exist in approximately 50% of the general population due to cross reactive immunity induced by Common Cold Corona viruses. Such SARS-CoV-2 specific memory T cells are considered to be beneficial to the host, affording protection from infection, or reduction in disease severity, particularly in the face of absent or waning humoral immunity. Despite the disruption in operations and regulatory delays due to COVID-19 our project has been initiated, and we feel that a revision at this juncture to incorporate questions related to SARS CoV-2 are timely and important. In this revision we are proposing to incorporate a pilot study of SARS- CoV-2 seroprevalence and T cell memory in the context of original aims in the HIV+OP+ and the other 3 groups (HIV-OP+, HIV+OP- and HIV-OP-) being investigated for flu vaccine induced immune responses.",2021,2025,N/A,153500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Clinical trials for disease management | Characterisation of vaccine-induced immunity,2020 +C15150,1R21AI158788-01,Host inflammatory response to SARS-CoV-2,"Each year, humans encounter a variety of seasonal corona viruses that cause minor symptoms similar to the common cold. In contrast, SARS-CoV-2, which is responsible for COVID-19 (coronavirus disease 2019), has caused more than 110,000 deaths in the United States alone as of June 4, 2020. For unknown reasons, COVID- 19 disease severity is extremely variable, with many infected individuals experiencing mild symptoms including sore throat, headache, and cough or no symptoms at all. However, a significant number of infected individuals experience severe disease, including acute respiratory distress syndrome, renal failure, cardiac arrest, and gastrointestinal distress. Importantly, SARS-CoV-2 infection can trigger a hyperactive immune response that results in a cytokine storm, which is a massive release of pro-inflammatory molecules that can cause fatal tissue damage and likely causes the most severe disease symptoms. What triggers and regulates a cytokine storm is unclear, and studies are needed to reveal the processes by which SARS-CoV-2 induces inflammation, and how SARS-CoV-2 infection imparts COVID19 disease. Thus, the overarching goal of this proposal is to determine how inflammatory responses to SARS-CoV-2 are generated. To address this goal, we propose the following Specific Aims: 1. Define the inflammatory cytokine response induced by SARS-CoV-2. We will evaluate cytokine production from cells infected with SARS-CoV-2 using cell lines derived from lung and immune cells that populate the lung. Additionally, because severe COVID-19 patients present with elevated levels of the cytokine IL-1β and because IL-1β is released following the inflammatory form of cell death known as pyroptosis, we will assess the ability of SARS-CoV-2 to stimulate pyroptosis. We will then use CRISPR-based gene knockout and pharmacologic inhibitors to map the molecular pathways required for production and release of the observed cytokines. 2. Determine the inflammatory transcriptome across infected and bystander cells in propagating and amplifying inflammatory responses to CoV2. Using single cell RNA sequencing, we will assay mixed populations of cells with infected and non-infected (bystander) cells to determine how virus infection imparts inflammatory gene expression and how inflammatory signals from infected cells affect neighboring uninfected cells to amplify the inflammatory response. Sequencing and bioinformatics analyses will be conducted by the Gale lab transcriptomics and computational biology team, and results will be validated by complimentary techniques. From these studies, we expect to reveal the inflammatory cytokine signaling events following SARS-CoV-2 infection. These studies will also provide biomarkers to identify patients susceptible to cytokine storm and will identify gene or gene network/pathway targets to inform strategies to treat COVID-19 disease.",2021,2023,N/A,264750,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2021 +C15151,1R21AI164001-01,COVID-19 comorbidity studies in Syrian hamster models,"PROJECT SUMMARY The pandemic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus can cause severe and even fatal infections in some patients, primarily those with comorbidities such as hypertension, diabetes mellitus, obesity, and cardiovascular disease. In addition, immunocompromised patients are also at a high risk of severe COVID-19, the disease caused by SARS-CoV-2. Animal models are vital for the testing of preventative and therapeutic approaches to COVID-19, but models that recapitulate the major comorbidities associated with COVID-19 are lacking. Recently, we established Syrian hamsters as a robust animal model for COVID-19 research. Building on our work with this model, we here plan to develop and evaluate diabetic (Aim 1), obese (Aim 2), cardiomyopathic (Aim 3), and immunocompromised (Aim 4) Syrian hamsters for COVID-19 research. For Aim 1 ('To evaluate diabetic Syrian hamsters for COVID-19 research'), we have already demonstrated our ability to generate diabetic Syrian hamsters by treating them with streptozotocin, a drug commonly used to establish diabetic animal models. A high-fat diet will be used to generate obese hamsters for studies in Aim 2 ('To establish obese Syrian hamsters for COVID-19 research'). Studies in Aim 3 ('To evaluate cardiomyopathic Syrian hamsters for COVID-19 research') will be conducted with BIO14.6 Syrian hamsters, an established cardiomyopathic disease model. An immunocompromised status will be induced by treating animals with cyclophosphamide (a drug commonly used to induce immunosuppression) for studies in Aim 4 ('To establish immunocompromised Syrian hamsters for COVID-19 research'). Specific markers, such as blood glucose levels (for diabetes), leptin levels (for obesity), troponin T levels (cardiovascular injury) and leukocytes counts (for immunosuppression) will allow us to monitor the disease states. Animals will then be infected with SARS-CoV- 2, and virus titers in different organs will be measured at different timepoints post-infection. In addition, we will measure the duration of virus shedding and the efficiency of virus transmission, both of which may be increased in co-morbid compared with healthy SARS-CoV-2-infected animals. We will also assess the susceptibility for reinfection with SARS-CoV-2 of both healthy and co-morbid Syrian hamsters. The comorbidities tested here result in chronic inflammation and/or impaired immune responses. Therefore, the levels of several pro- inflammatory cytokines and antibodies to SARS-CoV-2 in serum samples from these hamsters will be evaluated. Collectively, we will establish and test several Syrian hamster comorbidity models for SARS-CoV-2 research. Our data should provide a solid platform for the use of co-morbid Syrian hamster models in the testing of vaccines and antiviral compounds for SARS-CoV-2.",2021,2023,N/A,194375,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +C15152,1R01AI160961-01,Engineering protease-resistant antiviral peptide inhibitors for SARS-CoV-2,"No vaccines or treatments for SARS-CoV-2 are yet available. A simple prophylactic antiviral strategy would protect naïve individuals from infection now. In the future, when vaccines should be available, a prophylactic antiviral will be essential for individuals who do not mount a suitable immune response. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viral diseases. The entry/fusion process for CoV (including SARS-CoV-2) is mediated by the viral envelope glycoprotein (S). Concerted action by the receptor-binding domain and the fusion domain is required for fusion. Upon viral attachment (and uptake in certain cases), large-scale conformational rearrangements occur in the fusion domain, driven by formation of a structure that couples protein refolding directly to membrane fusion. The formation of this structure can be targeted by fusion inhibitory peptides (C-terminal heptad repeat or HRC peptides) that prevent proper apposition of the HRC and HRN domains in S. We have found that conjugation of a lipid to an inhibitory peptide directs the peptide to cell membranes and increases antiviral efficacy. Analogous lipo-peptides prevent infection by several viruses (measles, Nipah, parainfluenza, influenza), and can be administered via the airway. Treatment is effective for some of these even several days after infection. In addition, we have shown that modifying the backbone of an HRC peptide via periodic replacement of α-amino acid residues with β- amino acid residues generates α/β-peptides that retain antiviral potency (toward HIV or parainfluenza) but are highly resistant to proteolysis. We recently generated an HRC lipopeptide that is effective against both SARS- CoV2 and MERS live viruses in vitro, blocks spread of SARS-CoV2 in human airway tissue, and inhibits transmission of SARS-CoV-2 between ferrets in direct contact. Here we propose to combine the lipid conjugation and backbone-modification strategies to generate potent inhibitors of SARS-CoV2 infection that display a long half-life in vivo. 1. Optimize the antiviral potency and bioavailability of SARS-CoV-2 HRC peptide fusion inhibitors via rational molecular engineering. Antiviral efficacy of α/β-lipopeptide candidates will be measured in quantitative in vitro assays, in authentic virus infection, and in a human airway model. 2. Evaluate the protection afforded by new backbone-modified α/β-lipopeptide fusion inhibitors against SARS-CoV-2 infection in hamsters. Analysis of in vivo biodistribution and toxicity of backbone modified S- CoV-2 α/β-lipopeptide fusion inhibitors and assessment of in vivo potency and resistance mechanisms will lay the foundation for a safe and effective SARS CoV-2 fusion inhibitor for coronavirus prevention and therapy.",2021,2026,N/A,773390,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15153,1R21EB031466-01,Paper-COVID - Platform for High-throughput SARS-CoV-2 Screening and Contact Tracing,"Abstract At present, most of the diagnostic testing for COVID-19 has been done through local sampling of those who are symptomatic followed by centralized laboratory testing - returning results in 3-4 days. This is now supplemented by several point-of-care (PoC) systems who can perform the same test on site, returning the result much quicker, but at much lower throughput. To return many elements of the US economy to closer to normal function, such as international air travel, large-scale employers, and campus-based institutes of higher learning, will require us to shift from diagnostic testing to large scale, distributed, and repeated screening of asymptomatic (or pre- symptomatic) individuals. The length of time-to-result for traditional centralized testing and the relatively low throughput of existing PoC systems will make this a challenge. Here we propose to develop Paper-COVID - a modular platform that combines a clinically validated LAMP assay (already with FDA EUA approval) with a mobile phone based paper testing platform that enables much higher throughput screening for asymptomatic SARS-CoV-2 and facilitates automated contact tracing. The goal for this effort is to validate a novel sample processing technique, port the previously developed LAMP assay to a paper- based format, construct three modular prototype systems, and validate it on clinical samples from New York City.",2021,2023,N/A,432028,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15154,2R01DA003574-37A1,Risk Factors for AIDS among Persons Who Inject Drugs: HIV and COVID-19,"Abstract It is difficult to underestimate the potential public health significance of the COVID-19 pandemic for generating new outbreaks of HIV among PWID. While public health scale implementation of ""combined prevention and care for HIV"" among PWID has led to dramatic reductions in HIV transmission in many high-income countries, multiple outbreaks of HIV have also occurred, e.g., in the US, Western and Eastern Europe, and Israel. While there were distinct features of each outbreak, a number of common features were noted across the outbreaks, including: 1) community economic dislocations, 2) inadequate or interrupted HIV prevention services, 3) local introduction of new injectable drugs, and 4) homeless PWID as a very high-risk group. The COVID-19 pandemic and its associated lockdown/control measures appear to be re-creating the very conditions that generated HIV outbreaks among PWID in the pre- COVID-19 era. The recent FDA emergency use authorization of effective SARS-CoV-2 vaccines provides a critical opportunity to alleviate some-but certainly not all-of the threats to HIV prevention. However, important potential difficulties in rapidly vaccinating large numbers of PWID exist. We propose to examine relationships between HIV, COVID-19, and racial/ethnic disparities among PWID in NYC, a location that has experienced the world's largest local HIV epidemic among PWID, and one of the world's largest local COVID-19 epidemics, through four specific aims: 1. Assess short term (within 3 years) impact of the COVID-19 pandemic on HIV risk among PWID in NYC, including potential increases in critical bio-behavioral risks (composite risk for HIV transmission and composite multi-person risk for HIV acquisition). 2. Monitor SARS-CoV-2 vaccination over time among PWID in NYC. Identify factors associated with receiving vaccination, including 'underlying health conditions,"" socio-demographics, particularly race/ethnicity and employment, vaccine awareness and attitudes, and across patterns of drug use. Examine peer, family and ""trusted sources"" influences on receiving vaccination. Educate participants on SARS-CoV-2 vaccines, including availability, types, side effects and scheduling. Assess the extent to which ""herd immunity"" is being achieved among PWID. 3. Utilize antibody testing to estimate past and incident COVID-19 infection among PWID, identifying risk factors for infection, including race/ethnicity, and whether practicing protective behaviors is associated with lower seroprevalence. 4. Using principal component analysis (PCA), examine relationships between multiple health problems and social determinants of health among PWID in NYC, including HIV, COVID-19, HCV, opioid and stimulant use, drug overdose, homelessness, and economic and food insecurity, during the COVID-19 pandemic. Examine patterns of racial/ethnic disparities among the clusters of health and social determinants of health.",2021,2025,N/A,792422,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Drug users | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Policies for public health, disease control & community resilience",Immunity | Prognostic factors for disease severity | Approaches to public health interventions,1994 +C15155,1R21EB032117-01,Rapid Sample Preparation and Ultrasensitive Detection of COVID-19 in Human Saliva,"Project Summary The coronavirus disease 2019 (COVID-19) - caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - is a global pandemic with worldwide cases of over 35 million and a death toll of over 1 million people. In the United States, there are a total of over 7.5 million cases with over 210,000 deaths as of October 2020. The ability to identify COVID-19 infected patients rapidly, accurately, and cost-effectively is of paramount importance to control the disease outbreak. The two different types of COVID-19 tests are diagnostic tests and antibody tests. Specifically, the diagnostic tests can only identify active COVID-19 infected patients; the antibody tests can only indicate prior COVID-19 infections but not active cases. These diagnostic tests include quantitative reverse transcription polymerase chain reaction (qRT-PCR) and rapid antigen tests. In particular, the qRT-PCR is currently the most sensitive method (down to ~100 copies/mL) but can take >12 hours to perform and require trained personnel, specific reagents, and expensive machines. The rapid antigen tests provide results within 30 minutes, but these tests require the samples to contain high virus concentration (i.e., >107 virus particles/mL) leading to increasing chances of false-negative cases. In addition, one common example of the antibody tests is the enzyme-linked immunosorbent assay (ELISA). This test only applies to patients who have already developed the antibodies, which could take several days to weeks. Thus far, no single tests can detect both active and previously COVID-19 infected cases. The objective of the proposed research is to develop a proof-of-concept rapid and ultrasensitive virus-detection platform termed viral-ID, which is capable of simultaneous detecting the SARS-CoV-2 RNA and antibodies inside saliva for the identification of both active and previous COVID-19 infections within a single test. Specifically, the viral-ID platform will allow for specific molecular targeting, separation, enrichment, and filtering, all carried out within a single saliva droplet utilizing the nature-inspired coffee ring effect. Targeting and detection of the viral biomarkers will be carried out by aptamer-functionalized nanoparticles and deep-learning-enabled surface- enhanced Raman scattering (SERS), respectively. Using synthetic SARS-CoV-2 RNA and antibody-spiked saliva as a model system, the goal of this research is to demonstrate a bio-analysis platform capable of rapid sample preparation and ultrasensitive detection of both viral RNA (~10 - 100 copies/mL) and antibodies (~femtomolar) in a saliva droplet within 30 minutes. If successful, our viral-ID platform will provide all-in-one and best-in-class diagnostic and antibody test in terms of speed, sensitivity, and specificity for the rapid screening of COVID-19.",2021,2024,N/A,229209,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15156,3U42OD010918-22S2,Equipment to facilitate expansion of MMRRC services related to gut microbiota and infectious diseases including SARS-CoV-2 and future infectious agents,"PROJECT SUMMARY An overarching goal of the Mutant Mouse Resource and Research Center at the University of Missouri (MU- MMRRC) is to optimize and refine mouse models so that biomedical research using these models can proceed rapidly and effectively. The MU-MMRRC also conducts resource-related research, often collaboratively, to further refine and develop mutant mice and capitalize on the power of mouse genetics and associated microbiota for biomedical research. This proposal enhances the capacity of the MU MMRRC to further characterize and refine mouse models through characterization of biological material and enhance our capability to examine the role of infectious disease and the gut microbiome. In the immediate future this equipment will enhance our ongoing and proposed studies of COVID-19. As part of previous supplemental funding, the MU-MMRRC has succeeded in advancing this mouse strain as a model for human COVID-19, characterizing viral growth and the development of acute disease following intranasal and aerosol infection of mice with variations in gut microbiota and prior infection, recapitulating the disease in humans. As new variants of SARS-CoV-2 emerge from human samples the K18-hACE2 mouse will play a key role in evaluating pathogenesis and escape of immunity. As of May of 2021, there have been nearly 32 million survivors of COVID-19 in the United States. As an acute local and systemic inflammatory response is known to cause long-term post-infectious diseases such as chronic pulmonary and neurological diseases, the equipment requested for supplement funding will permit the MU-MMRRC an ability to further characterize and refine the mouse model for the benefit of short- and long-term biomedical research. In addition, this equipment will help the MU-MMRRC expand its ability to phenotype other mouse models in line with its long-term research goals of characterizing and optimizing mouse models by examining the effects of differing microbiota. Current equipment available for use in the BSL3 and ABSL3 laboratories is limited across the nation, effectively slowing COVID-19 research during this pandemic. Expanding the capacity of the BSL3 equipment resources available to analyze infected samples will allow the MU-MMRRC to continue to play a critical role in the biomedical research community and promote studies of pathogenesis for COVID-19. The objective of this proposal is therefore to provide several key pieces of equipment that are expected to be of use not only to COVID-19 researchers, but also provide flexibility to other researchers in the region and nation for studying disease pathogenesis in mouse BSL3 models. The resulting expansion of capabilities will be critical to research on these devastating diseases and on mouse models in general. Crucially, this equipment has use far beyond the pandemic and has been specifically chosen to enhance the parent grant's research goals during this funding cycle and into future funding cycles. .",2021,2025,N/A,467993,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2000 +C15157,1R21EB031306-01,Selectively Replicating Trojan Virus Vectors as Programmable CRISPR-Based Antiviral Therapies,"PROJECT SUMMARY The COVID-19 pandemic has highlighted our long-standing vulnerability to new viral infectious diseases with which there is no acquired immunity. While vaccines and antiviral therapies can eventually be developed to treat many viral infectious diseases, these interventions require significant time and resources to acquire. This results in a critical period of time where there are no therapeutic options to slow the spread of the virus, besides physical countermeasures that have dramatic economic and social consequences. The truly alarming insight is that all of the vaccines and therapies we develop now against SARS-CoV-2 will be useless against the next cycle of viral outbreaks (e.g., influenza, ebola, etc.). There is a paramount need to fundamentally transform our approach to combating emerging viral diseases by developing antiviral strategies that can be rapidly deployed at the onset of a new viral outbreak. We propose a revolutionary new viral-antiviral technology that has the potential to target emerging viral pathogens at all stages of the disease outbreak cycle. This includes targeting viral pathogens in animal hosts prior to human transmission, preventing viral infections in healthy individuals, and treating ongoing viral infections. This new ""Trojan virus"" technology uses engineered viral vectors that imitate viral pathogens, yet contain potent CRISPR antiviral machinery that degrades pathogenic viral particles. These Trojan virus vectors have an incomplete viral genome that can selectively replicate only in previously infected cells by hijacking viral derived proteins, which it uses to multiply and spread throughout the infected areas of the body. The spread of the Trojan virus acts to prevent viral infection in healthy tissue by targeting invading viral particles, while at the same time suppressing active sites of viral infection. The integration of CRISPR antiviral technology into Trojan virus vectors allows the system to be reprogrammed to target new viral strains without extensive protein engineering or clinical testing, facilitating the rapid mobilization of the technology during viral disease outbreaks. The proposed research will focus on developing SARS-CoV-2 Trojan virus technology as a therapeutic option for active viral infections. The research will use engineered non-infectious cellular model systems to evaluate SARS-CoV-2 Trojan virus genome designs that can selectively replicate only in previously infected cells. We will determine the optimal strategy for incorporating CRISPR antiviral technology into the SARS-CoV-2 Trojan virus vectors, while identifying key CRISPR vulnerabilities in the SARS-CoV-2 virus. To validate that the genome engineering principles developed for the SARS-CoV-2 Trojan virus therapy can mitigate active viral infections, we will duplicate the approach to target the mouse hepatitis coronavirus (MHV-A59), tracking the effectiveness of the Trojan virus in murine model systems. If successful, our research will generate a functional SARS-CoV-2 Trojan virus therapy, validating the genome design in preclinical model systems, to establish the foundation for commercial development of the technology for use in the current and future SARS- CoV outbreaks.",2021,2023,N/A,612000,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15159,1R01DK130472-01,NK cell mobilization as a pathogenic etiology of SARS-CoV-2 gastrointestinal disease,"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of Coronavirus Disease 2019 (COVID-19) and its rapid global spread has led to an unprecedented global public health crisis. Currently, treatment options are very limited and vaccines against SARS-CoV-2 are still pending widespread use. Host immune responses to SARS-CoV-2 play a crucial role in the containment of the infection. Although SARS-CoV-2 is generally thought of as a respiratory disease, an unexpected consequence is severe complications of the gastrointestinal tract (GIT). Indeed, up to two-thirds of COVID-19 patients have some GIT symptoms and several lines of evidence suggest a breakdown of the epithelial barrier resulting in widespread inflammation. While recent studies in COVID-19 patients and nonhuman primate (NHP) models described T lymphocytes and antibody responses, less is known about natural killer (NK) cell responses in SARS-CoV-2 infection. Classically, NK cells are viewed as nonspecific effector cells of the innate immune system that play critical roles in defense against viral infections. However, besides their ability to rapidly eliminate virus-infected cells without the need for prior antigen sensitization, NK cells also exhibit adaptive immune functions. Different forms of adaptive capabilities have been identified among human NK cell subpopulations, including reports of true antigen-specific memory NK cells as well as adaptive NK cells with enhanced antibody-dependent functions. NK cells may be crucial for early containment of SARS-CoV-2 and formation of adaptive responses elicited by infection, yet uncontrolled NK response may also contribute to the hyperinflammatory responses observed in COVID-19 patients, including in the GIT. In this proposal we will use NHP models, which recapitulate viral replication, immune responses and disease pathology observed in human COVID-19 infection, to test the following hypotheses: (i) pathogenic inflammation in the gastrointestinal tract in COVID-19 is a consequence, in part, of dysregulated or exacerbated NK cell responses, and (ii) specific subsets of NK cells mediate potent anti-viral responses against SARS-CoV-2, associated with enhanced viral clearance and reduced disease severity. We will address these hypotheses through two specific aims: 1. Determine the contribution of systemic and GIT NK cell mobilization to SARS-CoV-2 pathogenesis and clearance in macaque models; 2. Evaluate the mechanisms by which specific innate and adaptive NK cell subpopulations modulate SARS-CoV-2 infection in the GIT. If successful, the results of these innovative studies will contribute new knowledge of human immune responses against SARS-CoV-2 and provide the rationale to develop novel immunotherapeutic approaches to target specific NK cell subsets that could substantially contribute to prevent and treat COVID-19.",2021,2024,N/A,402500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity | Disease models",2021 +C15160,1R56HL157632-01,Decoding the cellular mechanisms of COVID-19 severe disease susceptibility in patients with chronic respiratory disease,"PROJECT SUMMARY The new coronavirus (SARS-CoV-2) and associated disease (COVID-19) is a global threat to worldwide economies and public health due to its highly contagious nature and rapid spread. To develop optimal strategies for treatment of COVID-19, it is critical to understand the cell types and molecular mechanisms that mediate coronavirus infection, tissue propagation, and host immune response. As recently reported, both SARS-CoV and SARS-CoV-2 use the host ACE2 receptor protein and protease TMPRSS2 to gain cellular entry. High-throughput single-cell RNA-sequencing (scRNA-seq) and Assay for Transposase-Accessible Chromatin (scATAC-seq) now allow us to interrogate cell types and cell states at unprecedented resolution, which has led to groundbreaking discoveries in lung tissue biology, including our lab's and the Human Cell Atlas recent survey of nasal and lung epithelial cell types that co-express ACE2 and TMPRSS2 consistent with disease phenotype. It has been reported that individuals suffering from chronic respiratory diseases are more susceptible to COVID-19 severe disease. We propose to leverage our expertise in lung biology, single-cell analysis, and unique access to lung tissue at Mount Sinai from COVID-19 patients with chronic respiratory disease comorbidities to define the cell types and regulatory mechanisms that mediate COVID-19 disease susceptibility due to SARS-CoV-2 infection, propagation and interplay with the host immune response. Towards this goal, we will perform scRNA-seq, scATAC-seq, and spatial transcriptomic sequencing of multiple infected and non-infected lung regions in 25-30 patients with COVID-19 and chronic obstructive pulmonary disease comorbidity following autopsy. The single-cell resolution data will allow us to characterize the repertoire of SARS-CoV-2 infected cell and surrounding stromal and immune microenvironment and how they contribute to developing COVID-19 severe disease. Analysis of scATAC-seq data from matched lung regions will identify the key transcription factors and regulatory mechanisms driving the expression programs related to viral infection, host immune response, and severe disease susceptibility. Finally, integration of ligand-receptor pair expression and spatial transcriptomics information will elucidate at greater resolution and scale how cell- cell interactions and tissue pathology are altered after coronavirus infection. Single-cell characterization of the cell types, immune response, and regulatory mechanisms of infection will improve our understanding of virus- host interactions and COVID-19 severe disease susceptibility in patients with chronic respiratory disease. This will, in turn, provide mechanistic insight towards discovering new therapeutic targets that specifically benefit COVID-19 patients with pre-existing respiratory conditions.",2021,2022,N/A,839491,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15161,1R01AI158911-01A1,"Cohort and biomarkers for COVID-19 severity, natural history, and reinfection","Summary As the COVID-19 pandemic continues, there is an urgent need to better understand the illness and host responses. In spring 2020, we established two cohorts of U.S. healthcare workers (HCW), a particularly hard- hit frontline community, to understand the characteristics of the illness and to identify predictors of poor outcomes, as well as of long-term sequelae. With the current study phase ending, extending follow-up activities in these well-characterized cohorts is critical to monitor the evolution of the infection and its sequelae in a rapidly evolving situation, which now includes vaccination and emergence of virus variants. In this time- sensitive proposal, we extend the follow-up period for an additional 3 years, allowing us to answer important epidemiological and mechanistic questions about infection, symptoms, long-term outcomes, and protective immunity. In Aim 1, we will define biomarkers of SARS- CoV-2 symptom onset and severity, capitalizing on serial biospecimens collected from cohort subjects prior to and during early stages of infection. We will test the hypothesis that symptom onset and severity correspond to baseline differences in pre-existing factors, including oral virome characteristics and peripheral blood transcriptome. We also will test whether, among SARS-CoV-2+ individuals, progression of illness severity can be predicted by analysis of early biomarkers at the time of diagnosis, including inflammatory biomarkers, immune cell populations, and organ-specific biomarkers of dysfunction, such as cardiac enzymes and coagulation factors. In Aim 2, we will examine long- term sequelae of asymptomatic and symptomatic COVID-19 infections. We will assess evidence of sustained physiological dysregulation up to 3 years following SARS-CoV-2 infections of varying severity (including asymptomatic), focusing on longitudinal biomarkers and pulmonary function. We will examine whether some infected individuals have persistent abnormalities in immunologic, virologic, and end-organ biomarkers and pulmonary function, compared to pre-infection biomarker and uninfected comparison subjects. We also will assess whether persistent abnormalities in biomarkers are associated with prolonged convalescence and reduced pulmonary function. In Aim 3, we will identify serum markers persisting after acute infection that may confer protective immunity. Using sera from SARS-CoV-2+ individuals, we will characterize the spectrum and functions of anti-SARS-CoV-2 antibodies and their relation to immune protection in the cohort as well as in an innovative ex vivo lung slice model. We will specifically examine variation in magnitude, duration, function, and spectrum of antibody responses in relation to severity of initial clinical infection. We will test the hypothesis that anti-SARS-CoV-2 antibody concentrations and protective functions are associated with lower rates of subsequent re-infection in cohort participants, as affected by vaccination status. The biospecimens (currently >40,000) from these cohorts will be available for collaborative studies.",2021,2024,N/A,784970,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +C15162,3R01HD089957-04S1,Determining the impact of COVID-19 vaccination on the menstrual cycle,"Project Summary This supplement to the parent award R01HD089957 will use several large preexisting US-based datasets to determine the impact of COVID-19 vaccine on menstrual health. While the parent award focuses on menstrual cycle changes with direct measures of ovulation and obesity as the main exposure, this supplement will focus on the COVID-19 vaccine as the main exposure, menstrual cycle changes, and indirect measures of ovulation. We will utilize similar scientific methods approved of in Specific Aims 1 and 2 of the parent award including prospective tracking of the menstrual cycle using validated measures and the inclusion of reproductive-age women of varying body mass index with regular menstrual cycles not using hormonal contraception. Public concern is mounting regarding the possible association between COVID-19 and menstrual health. This concern could lead to vaccine hesitancy for individuals and their families; a threat to achieving sufficient rates of vaccination and enabling windows of opportunity for the development of additional virulent variants. Menstrual cyclicity is an overt sign of health and fertility. Thus, our ability to gain a greater understanding of whether or not an association exists between COVID-19 vaccine and menstrual health is critical for the physical and mental well-being of those who menstruate, their community, and our greater public health. The goal of this supplement ""COVID19 vaccination and Menstruation"" is to determine if COVID-19 vaccination causes menstrual disturbances. Our primary outcome is the within-woman difference in mean menstrual cycle length (in days) pre- and post-vaccination or unvaccinated as well as secondary outcomes related to menstrual cycle timing and severity of vaccine response and changes in menstrual characteristics (e.g. flow, length, pain, associated symptoms, intermenstrual bleeding). We will perform a retrospective analysis of prospectively tracked menstrual cycle data utilizing validated measures pre- and post-COVID-19 vaccination or over similar time period for the unvaccinated group. We will develop a multi-variable logistic regression model considering all available potential confounders including but not limited to vaccine type, BMI, age, race/ethnicity, life stressors, etc. Our team has received the commitment of two leading online menstrual cycle tracking platforms with the built-in user approval to provide this de-identified data for research purposes plus the ability to survey these users to obtain additional data. As of June 2021, they report a cumulative number of active US reproductive age users with 'natural' cycles (no hormonal contraception) of approximately 2 million.",2021,2022,N/A,296124,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Adverse events associated with immunization,2016 +C15163,1R01HL158669-01,Hypertension augmented COVID-19 through renin-induced internalization of platelet-ACE2 / SARS-Cov-2 complexes,"Hypertension, for unknown reasons, is a primary co-morbidity risk factor for poor COVID-19 outcomes. SARS- Cov-2 breaches the lung blood-air barrier to spread among organs inducing endothelial cell dysfunction and multi-organ thromboembolism. ACE2 is the high affinity receptor for SARS-Cov-2 with TMPRSS2 cleavage then enabling fusion. However, ACE2 and TMPRSS are not co-expressed by all SARS-Cov-2 infected organs. We discovered human platelets express ACE2 and TMPRSS, bind SARS-Cov-2 spike protein, and internalize ACE2-spike protein complexes. SARS-Cov-2 RNA accumulates within platelets. Platelets are activated in essential hypertension, transgenic renin expression stimulates fibrosis and coagulation, and inhibition of coagulation blocks renin fibrosis. The direct renin inhibitor Aliskiren blocks thrombosis in hypertensive animals, so renin intercalates into coagulation to initiate thromboembolic disease. We discovered cells releasing prorenin stimulate explosive platelet activation, but in a unique way; the onset of activation was very delayed, and activation was always maximal. Mechanistically, prorenin interacted with quiescent platelets promoting escape of intracellular phosphatidylserine onto the platelet surface. Phosphatidylserine organizes tenase and prothrombinase coagulation complexes, forming factor Xa and then thrombin that explosively activated the platelet PAR1 thrombin receptor. Aliskiren abolished phosphatidylserine expression, thrombin formation, and thrombosis. This establishes renin as a novel, direct platelet agonist. Platelets displaying surface phosphatidylserine are rapidly cleared by engulfment by endothelial cells and perivascular macrophages of the reticuloendothelial system of liver, lung, and spleen. We postulate hypertension and renin expression promotes phosphatidylserine display on platelets, initiating coagulation and platelet activation, but also promoting rapid platelet clearance. This, we postulate, internalizes SARS-Cov-2 into cells that need not express ACE2 or TMPRSS2, themselves. Aim 1. Test the hypothesis that renin-activated platelets are entry vectors for SARS-Cov-2 into endothelial cells and macrophages of the reticuloendothelial system. Aim 2. Test the hypothesis renin-stimulated platelet turnover in vivo introduces SARS-Cov-2 pseudotyped lentivirus-platelet complexes into diverse organs. This project will establish a functional connection between hypertension and SARS-Cov-2 infection, identify renin activated platelets as novel SARS-Cov-2 entry vectors, and define a basis for altered platelet clearance in renin-clamped hypertensive mice. This provides a translational basis for Aliskiren use to normalize hypertension risk in COVID-19, elucidates novel approaches to suppress SARS-Cov-2 organ infection and damage, and establish circulating platelet ACE2 expression as a measure of risk for COVID-19 multi-organ damage.",2021,2025,N/A,572341,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15164,1R21AI163912-01,Assessing the Risk of SARS-CoV-2 Remdesivir Resistance,"PROJECT SUMMARY The rapid spread of the SARS-CoV-2 pandemic around the globe has led to an urgent and ongoing evaluation of therapeutic strategies for the treatment of Coronavirus Disease 2019 (COVID-19). While a handful of host- directed therapies are being used for the treatment of severe disease, including monoclonal antibodies and dexamethasone, there is only one antiviral with emergency use authorization, the nucleotide analog remdesivir (GS-5734). Remdesivir is thought to inhibit the viral RNA-dependent RNA polymerase, Nsp12, through nucleotide mimicry and early chain termination. As use of remdesivir for the treatment of COVID-19 escalates, it is essential to understand the nature and risk of developing antiviral resistance. We hypothesize that intra-host variation in Nsp12 could allow for the evolution of remdesivir resistance. In this exploratory grant, we propose to test this hypothesis by quantifying the SARS-CoV-2 viral diversity that arises in hospitalized patients over time with and without remdesivir treatment (Aim 1), and by determining the impact of known Nsp12 mutations on polymerase activity and sensitivity to remdesivir (Aim 2). In Aim 1, we will leverage a biobank of longitudinally collected nasopharyngeal swabs from hospitalized COVID-19 patients at Northwestern Memorial Hospital. Specimens were collected every 4 days after enrollment for up to one month, including specimens from 8 patients given remdesivir. We are continuing to collect specimens and intend to enroll an additional 50 COVID-19 patients over the coming months. Deep, whole genome sequencing of SARS-CoV-2 viruses from each specimen will be performed to classify the viral variants detected within each patient over time. The nature and extent of variation will be compared by time point, viral load, and treatment course as determined from medical record data. These studies will be complemented with deep sequencing of viruses produced ex vivo in the presence of varying concentrations of remdesivir. Overall, this work will determine the nature and extent of SARS-CoV-2 intra-host variation that develops in hospitalized patients and will determine the impact of remdesivir treatment on that variation. In Aim 2, in vitro oligonucleotide extension assays will be used to assess the impact of previously described Nsp12 mutations on polymerase activity and remdesivir efficacy. Documented mutations near the remdesivir binding pocket and Nsp12 active site, newly documented haplotypes arising in our patient population, and Nsp12 mutants found to be under selective pressure will be assessed first for polymerase activity followed by remdesivir sensitivity. The phylodynamic histories of impactful mutations and haplotypes will be followed to look for evidence of selection in the population. Together, these results will assess the risk of emergent remdesivir resistance and additionally identify potential resistance mutations for active monitoring.",2021,2023,N/A,239500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Supportive care, processes of care and management | Prophylactic use of treatments",2021 +C15165,1R21AI163708-01,Biophysical characterization of SARS-CoV-2 spike protein - receptor interactions,"PROJECT SUMMARY/ABSTRACT The current pandemic of Coronavirus Disease-2019 (COVID-19) has had devastating impacts across the world. In order to enter human host cells, SARS-CoV-2, the virus causing COVID-19, uses its surface spike (S) protein to attach to host cell surface receptors. Besides the best-known receptor, ACE2, a number of cell surface proteins, including CD147, neuropilin-1 (NRP1) and DC-SIGN/L-SIGN, have been reported to bind to S protein and mediate SARS-CoV-2 entry. Consistently, our preliminary studies using single-molecule force spectroscopy show that CD147, NRP1 and L-SIGN can bind to the SARS-CoV-2 S protein with comparable affinities to those of ACE2. Therefore, the possible multiple receptor utilization could, at least partially, explain the broad tissue tropism and systemic complications of SARS-CoV-2 infection. However, it remains puzzling how the S protein can bind to these structurally diverse molecules with high affinity. In addition, our all-atom structural modeling data shows that most of the S protein surface is covered by glycans, and only when the S protein's receptor binding domain (RBD) is in the ""up position"" can it bind to a receptor without glycan interference. Therefore, we hypothesize that limited regions on the S protein that are not covered by glycans, including the RBD in up position, as well as the S1/S2 junctional region, may be responsible for binding all the receptors. In the proposed work, we will systematically test the hypothesis using combined approaches of single-virus force spectroscopy, all- atom molecular modeling and simulation and pseudovirus internalization/entry assays. Moreover, since SARS- CoV-2 has two entry routes (direct viral-host membrane fusion or endocytic/macropinocytic internalization followed by endosomal entry), the exact entry pathways that these receptors mediate are not yet clear. The proposed research will determine whether every individual interaction is more prone to mediate direct viral-host membrane fusion or viral endocytic/macropinocytic internalization. Two specific aims will be pursued: 1) to characterize S protein interactions with host cell membrane receptors and 2) to determine the structural basis of S protein's broad receptor recognition. The study will elucidate the structural and biophysical mechanisms behind S protein's receptor recognition and utilization. Successful completion of this work will allow us to identify new targets for antiviral therapies to treat the systemic complications of COVID-19.",2021,2023,N/A,199748,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15166,1R21ES033598-01,Per- and Polyfluoroalkyl Substances (PFAS) Exposures and COVID-19 Vaccine Effectiveness,"PROJECT SUMMARY/ABSTRACT Infection with SARS-CoV-2 and its associated disease state, COVID-19, has resulted in over 374,000 deaths in the United States to date. Vaccines protecting against COVID-19 have recently received FDA emergency use authorization and are being administered to high-risk individuals with wider dissemination to follow. Exposure to per- or polyfluoroalkyl substances (PFAS) is associated with reduced immune response following vaccination against other infections, but its effect on COVID-19 vaccine effectiveness is not known. We have a time-sensitive opportunity to determine the effect of serum PFAS on response to COVID-19 vaccination, building on a unique study in ~2,000 healthcare workers, first responders and other essential workers in Arizona without prior COVID- 19 infection, many of whom have either recently been vaccinated or will be vaccinated in the coming months, supplemented by ~700 additional participants from a similar study in both Arizona and Florida. Our objective in this application is to determine the effects of PFAS exposure levels on COVID-19 vaccine effectiveness. Our central hypotheses are that increased PFAS serum concentrations will: 1) reduce initial SARS-CoV-2 antibody titers following COVID-19 vaccination; 2) increase the rate of longitudinal decline in antibody titers; and 3) increase the frequency of COVID-19 during a nine-month period following vaccination. The rationale for this research is that successful completion can be expected to provide new data about the immune effects of PFAS exposure. We will test these hypotheses through two regular and one exploratory specific aims: 1) Evaluate the association of serum PFAS with initial SARS-CoV-2 antibody titers following COVID-19 vaccination; 2) Evaluate the association of serum PFAS with longitudinal decline in SARS-CoV-2 antibody titers following COVID-19 vaccination; and 3) Evaluate the association of serum PFAS concentrations with frequency of COVID-19 following vaccination. For aims 1 and 2, we will select 600 of our Arizona study participants for measurement of serum PFAS following COVID-19 vaccination. As part of the study, these participants will also provide serum for measurement of SARS-CoV-2 antibodies every three months for at least nine months, and provide respiratory samples weekly for PCR testing to identify SARS-CoV-2 infection. For the exploratory aim, we will identify all COVID-19 cases following vaccination in both the Arizona and Florida study populations, and for each case select five matched controls who received COVID-19 vaccination but were not infected with SARS-CoV-2. Serum PFAS levels will be compared across the cases and controls. At study completion, we will have documented the effects of PFAS exposure on SARS-CoV-2 antibodies following COVID-19 vaccination and the frequency of COVID-19 cases following vaccination. The proposed research is significant given the potential for PFAS exposure to reduce the effectiveness of COVID-19 vaccines. The proposed research is innovative as it is the first to our knowledge to determine the association between serum PFAS levels and measures of COVID-19 vaccine effectiveness.",2021,2023,N/A,261135,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Emergency Responders | Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians | Dentists and dental staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C15167,5R01AI110700-07,"Cell entry, cross-species transmission and pathogenesis of novel coronavirus from","The 21st century has recorded the emergence of three highly pathogenic respiratory coronaviruses, including Severe Acute Respiratory Coronavirus (SARS-CoV) in 2003, the ongoing Middle East Respiratory Coronavirus (MERS-CoV) in 2013 and a novel SARS-like coronaviruses SARS-CoV2 (SARS2) in Wuhan, China in Dec 2019. SARS2 causes COVID19, a severe acute respiratory distress syndrome (ARDS) and has infected 95000 individuals with ~20% severe cases and a ~3% mortality rate, resulting in over 3700 deaths. In the elderly, mortality rates approach 15%. The overall program goals are to identify the viral and host determinants, which regulate the atomic-level interactions between the SARS2 S-glycoprotein and various ACE2 receptor and associated entry components such as cellular proteases. The impact of these studies are high, as these interactions regulate 2019-nHCoV species specificity and host tropism, which play critical roles in viral pathogenesis and inform the evolutionary pathways leading to virus emergence and spread in humans and perhaps other intermediate hosts. In parallel, we apply these and other findings to developing robust mouse models of SARS2-mediated human disease, which is critical for not only evaluating viral pathogenesis but also for future testing of antiviral drugs, immunotherapeutics and vaccines.",2021,2025,N/A,748081,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Disease models",2015 +C15168,1R01AI160662-01A1,Temporal Transcriptomics in Hospitalized COVID-19 Patients from Disparately Impacted Ancestral Groups for Therapeutic Discovery,"PROJECT SUMMARY SARS-CoV-2 is a novel coronavirus which causes COVID-19, a disease that has infected >46M people resulting in >1.2M deaths by 31 October 2020. The US has the highest global case count (>9.2M) and mortality (>230K) with recent record-setting daily cases and hospitalization rates across the country. This has been particularly true for New Mexico (NM) where cases and hospitalizations are surging again. It is now recognized that certain minority groups, i.e., African Americans, Hispanics, and American Indians/Alaska Natives (AI/AN), suffer disproportionally from COVID-19. NM has the highest proportion of Hispanic ancestry, and one of the largest AI/AN populations, with these two groups representing 47% and 26% of the cumulative cases, respectively. After adjusting for population size, the AI/AN group has 3.3-fold higher cumulative case rates, 7.9-fold higher hospitalizations, and 10.6-fold higher age-adjusted mortality rates. As the only academic medical center and Level 1 Trauma Center in the state, the University of New Mexico Hospital (UNMH) has played a principal role in caring for patients with COVID-19. UNMH is the primary tertiary care referral center for NM and surrounding regions, including the Navajo Nation and other tribal lands. As such, we are uniquely positioned to address important gaps-in-knowledge about the molecular basis of increased COVID-19 disease severity and mortality in disproportionally affected ancestral groups. In mid-February, the UNM Center for Global Health assembled a multidisciplinary group of investigators to address the challenges of COVID-19. As of 31 October, we have recruited and followed 167 hospitalized patients with COVID-19, offering an opportunity for rapid translational impact within the planned three-year study. The experimental strategy parallels our ongoing R01 studies in African children utilizing mRNA-Seq to identify novel therapeutic targets (PI: Perkins). State-of-the-art methodologies and modeling efforts in place in our laboratories will be applied to create solutions for improving outcomes in COVID-19 patients. This will be achieved by following non-severe and severe COVID-19 patients across hospitalization from different ancestral groups to successfully complete three specific aims: 1) determine the impact of SARS-CoV-2 viral load dynamics on disease severity, 2) identify gene expression networks that mediate disease severity, and 3) identify prioritized FDA-approved compounds that modulate gene networks associated with enhanced disease severity for use in future clinical trials. In a short time, we have generated extensive data on viral load dynamics and identified novel gene networks with target-compound matches. We present data showing that individuals of AI/AN descent have significantly higher and protracted viral loads in peripheral blood and more severe disease, despite comparable co-morbid factors with other groups. The proposed investigations have direct translational impact, particularly in disproportionately affected ancestral groups by defining the host immune response to SARS-CoV-2, identifying biomarkers for risk assessment, prognosis, and disease progression, and fostering drug repurposing to reduce disease severity and mortality.",2021,2024,N/A,751987,Human Populations,Black | Other,Unspecified,Unspecified,Indigenous People,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Research to inform ethical issues","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +C15170,3P20GM121293-05S1,Center for Translational Pediatric Research (CTPR),"PROJECT SUMMARY The continuing emergence and subsequent circulation of SARS-CoV-2 variants across the world is of concern for the global effort of controlling the Coronavirus Disease (COVID)-19 pandemic. Despite a high-burden of disease overall, Arkansas has been slow to sequence viruses associated with infections in the state. For this proposal, our Center for Translational Pediatric Research (CTPR) Center of Biomedical Research Excellence (COBRE) and Arkansas IDeA Network of Biomedical Research Excellence (INBRE) have partnered together to deliver sustainable SARS CoV-2 genomic surveillance data and analyses for the State of Arkansas. At the core of this proposal, we have built a powerful collaboration named the Arkansas Sequencing (ArkSeq) Consortium which includes the University of Arkansas for Medical Sciences (UAMS), Arkansas Children's Hospital (ACH), including Arkansas Children's Northwest and UAMS Northwest extensions, Baptist Health (BH) in Little Rock, drive-through centers across the State run by the Arkansas Department of Health (ADH), and Arkansas Children's Research Institute (ACRI). This consortium provides remnant viral transport media (VTM) that have been identified as positive for SARS-CoV-2. Our objective is to continuously monitor these samples for SARS- CoV-2 sequence diversity and viral phylodynamics and to provide actionable data back to the ADH and CDC regarding variants. Aim 1 of this proposal is to provide genomic surveillance for Arkansas. To fulfill this aim, we will use Illumina-based platforms to sequence at least 12288 samples from our ArkSeq Consortium for variants of concern (VoCs) over the next year with a goal to scale to all patients. We will obtain clinical information on these samples, including the subject's demographics (age, sex, race, ethnicity, county of residence, and zip code), date of collection, symptoms at the time of sampling, other respiratory viruses present at the time of positive result, and vaccination status (vaccine type and date of vaccination). This approach will allow us to answer the research questions: ""What are the relative levels of the different variants in Arkansas?""; ""How does this change over time?"" and ""How are different Arkansas variants distributed across different geographical regions, as well among racial, ethnic, gender, and/or age groups?"" In collaboration with the ADH and the CDC, we will integrate VoCs and other lineages from Arkansas into national databases. We plan to provide actionable sequencing information on current strains of SARS-CoV-2 that are circulating within Arkansas. To meet this goal, we are currently participating in the weekly SPHERES calls with CDC, and we are partnering with ADH and ArkSeq partners to have monthly meetings regarding identified variants. Upon successful completion of this proposal, we will have provided ~21 times more sequences from Arkansas to the databases than are currently available from our State, with many other samples maintained for future evaluation.",2021,2022,N/A,770000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2017 +C15171,1R01DK130465-01,Mechanisms of childhood obesity underlying the susceptibility to multisystem inflammatory syndrome in children (MIS-C),"PROJECT SUMMARY/ABSTRACT Unpredictability is the hallmark of Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is a severe pediatric complication of SARS-CoV-2 infection. MIS-C is distinct from COVID-19. It is not associated with pre-existing cardiopulmonary, autoimmune, or hematologic disorders. It can occur either during acute phase with detectable SARS-CoV-2 virus, or in the post-infectious period of several weeks after acute infection. Milder symptoms of MIS-C include fevers, rashes, and gastrointestinal symptoms, but can progress to cytopenias, coagulopathy, myocardial dysfunction, coronary aneurysms, and/or shock. We and others have found that MIS- C is associated with pediatric overweight and obesity, thereby identifying over 380 million children at risk for this disease. The mechanisms by which overweight and obesity influence the development of MIS-C are unknown. Until a vaccine against SARS-CoV-2 is globally available to all children, they will remain vulnerable to MIS-C. Our preliminary studies indicate that MIS-C is a highly inflammatory disease that incites more severe immune cell activation than COVID-19, particularly in overweight and obese children. Overweight and obese children with MIS-C had more T cell lymphopenia and T cell activation than their normal weight counterparts, suggesting an increased risk for more severe disease. Deleterious genetic variants increasing IFN and inflammatory signaling were exclusively found in patients with MIS-C, rather than severe COVID-19. This is a mechanistic counterpoint to defective IFN signaling associated with severe COVID-19 in adults. Our central hypothesis is that pediatric overweight and obesity prime interferon signaling, thereby increasing T cell activation and ultimately, the risk of MIS-C Aim 1 will elucidate how pediatric overweight and obesity drive immune cell dysfunction during MIS-C. The proposed studies will test the hypotheses that pediatric overweight and obesity are associated with more severe MIS-C, characterized by excessive interferon signaling and T cell activation. Aim 2 will identify mechanistic risk factors for MIS-C. The proposed studies will test the hypothesis that, even in the absence of infection, circulating immune cells from overweight and obese children exhibit an increased interferon signature that promotes T cell activation. We will develop a strategy for stratifying MIS-C by integrating genetic screening with measures of body mass index. Building on collaborations spanning over a decade and unique cohorts of children with MIS-C and/or obesity, our investigator team brings expertise in MIS-C, host immunity, pediatric obesity and endocrinology, and multiomics. This project will generate causal insights of how overweight and obesity influence the development and severity of MIS-C, with the goal of developing strategies for a population that remains at risk for this disease.",2021,2024,N/A,442500,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C15173,75N93021C00015-0-9999-4,CEIRR: COVID-19 Research Activities,"CEIRR will determine the molecular, ecologic and/or environmental factors that influence the evolution, emergence, transmission and pathogenicity of respiratory viruses, including coronaviruses such as SARS-CoV-2, and characterize the immune response to infection to improve understanding of the immune correlates of protection and cross-protection. CEIRR will carry out a host of activities, including cohort studies and human and animal sampling to further understanding of infection, transmission and vaccination; identification of immunological factors that determine disease outcome in the response to infection and vaccination; and studies to determine how viruses evolve, adapt and transmit between humans and at interspecies interfaces.",2021,2022,N/A,413497,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility",2021 +C15174,1R01AI161152-01A1,Serologic and Molecular Studies of human anti-hCoV antibody cross-immunity and protective responses among endemic HCoVs and SARS-CoV2,"Project Summary The emergence of the novel human betacoronavirus SARS-CoV2 in Wuhan, China in 2019 has rapidly evolved into a worldwide pandemic. Over a 100 million people have been infected and there have been several million deaths. There is also great disparity in the manner in which COVID-19 illness presents, from asymptomatic infection to death. COVID-19 illness in children is overall more mild or asymptomatic compared to adults. One hypothesis that may explain this disparity is that children have cross-immunity to SARS-CoV2 due to frequent early exposure to globally circulating human coronaviruses (HCoVs) that cause a milder respiratory illness. Whether there is some level of cross-immunity between the endemic HCoVs and SARS-CoV2 that carries into adulthood and can provide some level of protection from COVID-19 disease is the subject of this R01 application. Our primary goal is to provide serologic and molecular evidence of anti-HCoV/SARS-CoV2 spike (S) cross- reactive and neutralizing antibodies that can provide protection against SARS-CoV2 in vivo. We have an IRB- approved protocol to collect blood samples on 250 COVID-19 individuals. Our COVID cohort is comprised of 5 groups that includes adult and pediatric cancer patients, adult and pediatric healthcare providers and adults without COVID patient contact. In addition, we will study our pre-pandemic seasonal influenza cohort for evidence of pre-existing anti-SARS-CoV2 S Abs. In Aim 1 we will quantify the present of anti-S HCoV antibodies and quantitate their cross-reactivity to SARS-CoV2 S. The studies in subaim 1A will include FACS staining of S expressing cells and ELISAs of S subdomains for epitope mapping. In subaim 1B, selected plasma samples within each study group will be used for affinity column purification of plasma IgGs that will be passaged over and eluted from one of 4 HCoV or SARS-CoV2 spike columns and tested for cross-binding, cross-Fc effector activity and cross-neutralization activity. In subaim 1C, these purified IgGs will be tested in vivo in hACE2 mice for cross-protection against SARS-CoV2 challenge. In Aim 2 we will establish the molecular basis by which bi- directional immunity to among CoVs could provide cross immunity to HCoVs and SARS-CoV2 through common spike epitope recognition. In subaim 2A, we will perform memory B (mB) cell screening for presence of S cross- binding. Single mB cells that bind at least one hCoV S protein and SARS-CoV2 S will be isolated by FACS, their cognate VH/VL genes cloned, expressed as whole IgG1 mAbs and tested for cross-binding, virus neutralization and Fc effector activity against the different HoCoVs, SARS and SARS-CoV2. In subaim 2B, mAbs with cross- CoV activity will be tested in mouse and hamster models for protection against SARS-CoV2 challenge. In subaim 2C, we will adapt the novel LibraSeq technique to capture the single or multi-spike binding specificity, BCR repertoires and transcriptomes of selected Bm cells to study the potential different evolutionary origins that may exist between mono-spike and multi-spike binding cells. This R01 grant will provide proof-of-principle molecular studies of HCoV/SARS-CoV2 Ab cross-immunity that may aid in COVID-19 vaccine design.",2021,2024,N/A,903360,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +C15175,1R21AI161075-01,Develop novel inhaled neutralizing RNA therapeutics against COVID-19,"Project Abstract Despite various antiviral agents or symptom-alleviating interventions under development, unfortunately no effective drug treatment for COVID-19 have been readily identified so far. Given the desperate need for and willingness to try new therapeutic approaches during the COVID-19 pandemic, RNA-based therapeutics could prove to be an attractive option due to their rational design and relatively faster speed of development compared to conventional strategies. Utilizing our extensive experience and expertise in nucleic acid aptamer technology, we will seek to design and develop RNA aptamer-based drug candidates that can provide immediate neutralizing protection against SARS-CoV-2 infection. The SARS-CoV-2 binds to human angiotensin I converting enzyme 2 (ACE2) through its trimeric spike protein (S protein) on the virion, where after fusion of the viral membrane and host cell membrane occurs. Subsequently, the RNA virus will replicate its genome inside the cells and ultimately make new virions that will be secreted to infect other host cells. The S protein is the key target for the development of neutralizing antibodies (Abs), vaccine and therapeutics. The immediate objective of our project is to develop novel inhaled RNA aptamers that specifically bind to the conserved and functional essential elements of SARS-CoV-2 S protein, as viral neutralizing agents, to prevent viral entry and infection. Our central hypothesis is that the inhaled neutralizing RNA intervention will have utility for both pre-exposure prophylaxis and immediate post-exposure treatment to provide a 1st line of defense against SARS-CoV-2 and/or future SARS-CoV stains. In addition to their utility as stand-alone antagonists, the aptamer can also be formulated as cocktailed format or multivalent modality to maximize neutralization potency and breadth. The inhalation administration will further maximize delivery to the epithelial cilial cells of the upper and lower respiratory tract, the tissue sites of initial viral attachment and infection. To the end, we expect successful completion to lead to a translational stage and justify the use of inhaled neutralizing RNA therapeutics immediately in the clinic to protect 1st line health care workers and others at high risk of SARS-CoV-2 exposure. The proposed research is both significant and innovative, and could change current paradigms in the treatment of SARS-CoV-2 infection. The knowledge gained from this study can be rapidly deployed for combating a future strain evolution of SARS that may emerge as a human healthcare threat.",2021,2023,N/A,396000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +C15176,3R35GM133725-04S1,Spatiotemporal forecasting of COVID-19 by integrating machine learning and epidemiological modeling,"PROJECT SUMMARY/ABSTRACT In this ongoing COVID-19 pandemic, it is crucial to have an accurate and early prediction of the spread of highly infectious SARS-CoV-2. A correct prediction of the pandemic situation and future trends enables effective resource allocation and government policies to reduce the detrimental effect of COVID-19 on public health and economics. Although various epidemiological models have facilitated the prediction of the infection spread, their ensemble-averaging approach largely disregards critical information within the heterogeneity. Conventional epidemiological modeling is focused on the global average trends, which is limited in analyzing dynamic local information and does not allow local prediction due to spatial heterogeneity of the pandemic situations. Given the rapid changes of the COVID-19 pandemic, it is also challenging to take urgent responses to the new epidemiological data if we solely rely on human intelligence. Recently, machine learning (ML) is making tremendous progress and has shown that computers can outperform humans in analyzing complex high-dimensional datasets. Our lab has been addressing these challenges in cell biology by developing an ML platform for fluorescence live cell image analyses at the subcellular level. We established the method to deconvolve the subcellular heterogeneity of time series of cell protrusion, which identified distinct subcellular protrusion phenotypes with differential drug susceptibility. Thus, our goal is to leverage our ML platform to address these technical challenges in epidemiological modeling for rapid forecasting of COVID-19 spread at the county level in the United States. First, we will advance our ML platform for the deconvolution of spatial heterogeneity of COVID-19 dynamics. This method will integrate epidemiological models and ML to identify the clusters of US counties sharing similar temporal patterns. Second, we will apply our deep learning-based feature learning, where the deep neural networks learn the critical features guided by prior knowledge and well-established epidemiological mathematical models. This will allow us to generate fine-grained forecasting maps of Covid-19 spread. Our ML platform will bring unprecedented prediction power to epidemiology and enable us to take urgent responses to the current COVID-19 pandemic and future other infectious disease outbreaks.",2021,2024,N/A,318600,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing | Innovation,,,,United States of America,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2019 +C15177,3R01AI131424-05S1,Development of Sustained-Release Anti-coronavirus Nucleoside Phosphonate compounds,"Since the emergence of SARS CoV-2 in China in the fall of 2019, nearly 200 million cases of COVID-19 have been reported globally; over 4 million of these individuals have died. In the US, the virus has been responsible for over 600,000 deaths. Despite a good understanding of non-pharmaceutical interventions that mitigate viral transmission and the development of several highly efficacious vaccines, the global epidemic has continued at a brisk pace. Vaccine availability has been scant in resource limited settings and, even where it has been widely available for months, substantial segments of the public have declined vaccination. In addition, as new more transmissible viral variants emerge that are less susceptible to immunity stimulated by first generation vaccines, an increasing number of breakthrough infections have been noted. Although most of these breakthrough infections do not result in hospitalization, some do, and there is a significant concern that further immunological evolution will further compromise vaccine efficacy. Although further progress on the vaccine front is to be expected, highly effective and well tolerated antiviral agents are sorely needed. At present, the only two modes of antiviral therapy currently approved by the US Food and Drug Administration are Remdesivir and monoclonal antibodies directed at the viral spike protein. Both of these therapeutic modalities require parenteral administration, greatly limiting their general utility, especially in resource limited settings. In addition, as the viral spike protein has evolved within the human population, several of the monoclonals have lost their efficacy against new circulating viral variants. This evolution is expected to continue as critical viral epitopes are shaped by human immune responses generated during natural infection. In this supplement, we propose to apply our synthetic chemistry to the remdesivir base and other nucleosides to develop well-tolerated compounds with high levels of activity against the RNA polymerase of SARS CoV-2 and other coronaviruses that can be delivered orally and achieve uniformly therapeutic concentrations of the active triphosphate in a wide variety of relevant tissue types. If successful, we anticipate that these compounds could have broad medical applicability in patients with COVID-19 and other coronavirus infections.",2021,2022,N/A,169785,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Prophylactic use of treatments,2017 +C15178,1R21AI163282-01,DiagnosDisk - a highly sensitive point-of-care test for detecting SARS-CoV-2 antigen in saliva,"Project Summary/Abstract SARS-CoV-2, a global pandemic, has caused more than 6 million infections and 180,000 deaths in the United States alone during the past 7 months. Both the WHO and CDC emphasize the need for point-of-care (POC) tests to expand diagnosis of acute infections to control the pandemic (i.e. isolating infected individuals). The current gold standard test for diagnosing acute SARS-CoV-2 infection is reverse transcriptase polymerase chain reaction (RT-PCR) with nasopharyngeal samples. The assay is highly sensitive, but requires well-trained personnel for sample collection and locations with specialized equipment. Therefore, the turnaround time varies from one to few days, delaying isolation, contact tracing, and medical attention. These challenges can be addressed with lateral flow immunoassays (LFIA) to detect viral antigens in self-collected saliva samples. Compared to nasopharyngeal specimens, studies have demonstrated that assays with saliva samples are more consistent and the saliva itself may contain higher viral load. However, existing LFIA for detecting salivary antigens exhibit poor sensitivity (≤ 40%) caused by the use of small sample volumes and sample dilution. To achieve timely and accurate screening of suspected COVID-19 cases, this project aims to develop a rapid assay for detecting SARS-CoV-2 antigens in saliva with high sensitivity to meet WHO's target product profile. We hypothesize that using ≥500 µL saliva as the assay sample can significantly improve the sensitivity because a larger specimen volume provides more analytes for detection. The new test will employ temperature-responsive polymer-antibody conjugates in conjunction with DiagnosDisk, a novel flow-through assay device. The approach is innovative in in using enriched saliva specimens for more consistent assay results, enhancing antigen detection by scaling up the saliva specimen volume, and adopting the well- developed sandwich immunoassay for DiagnosDisk with temperature-responsive polymer reagents that simplify the design while maximizing the sensitivity. We will employ polymer-antibody conjugates that efficiently isolate analytes in saliva (Aim 1) and fabricate the DiagnosDisk device to accommodate larger volume saliva specimens to improve the detection limit (Aim 2). The sensitivity of the new rapid assay, which combines polymer-antibody conjugates and DiagnosDisk, will be evaluated using saliva specimens from COVID-19 positive and negative patients (Aim 3).",2021,2023,N/A,233250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15179,3U42OD012210-22S2,Enhancement of existing ABSL3 facilities to accommodate expanded mouse validation and phenotyping,"ABSTRACT & SCOPE OF WORK The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC-UC Davis) is pleased to submit this administrative supplement for up to 1 year of support in response to ORIP's participation in PA-20-272, ""Administrative Supplements to Existing NIH Grants and Cooperative Agreements"" specifically related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). This application addresses a number of the stated objectives of the call to support general and biocontainment- related alterations and renovations of existing facilities and to purchase equipment to facilitate COVID-19 and other infectious disease research in small animals. Specifically, this application requests funds to enhance and expand capacity and functionality of our existing ABSL3 vivarium and testing facility by 1) purchasing additional mouse caging and related husbandry equipment to double our ABSL3 biosafety housing, maintenance, and testing capacity for mice, 2) obtaining equipment that facilitates increased mouse handling and testing throughput for infectious disease research requiring ABSL3 containment, and 3) procuring laboratory instrumentation for virus preparation and trituration, and mouse challenge and phenotyping activities dedicated to infectious disease research, including SARS-CoV-2 and COVID-19. Funding of this project will accomplish 3 things. First, it will enable us to conduct additional and more complex mouse-related studies than we can currently perform simultaneously, thus accelerating and extending our abilities to respond to a greater variety of researcher needs and in a more timely manner. Second, it will allow us to conduct long-term studies on mouse models after infectious virus challenge, which will permit and catalyze research on aged mice and the pathophysiological consequences and complications of virus infection on the host, such as post-acute sequellae of COVID-19 (PASC). Third, it will permit efficiencies in virus challenge studies and consolidation of phenotyping activities within the ABSL3 facility, such as measuring body weight kinetics, assessing cardiac and lung function, performing necropsy and harvesting tissues (organs, cells, blood, intestinal contents, etc), and whole animal imaging. Together, these upgrades will significantly enhance our ability to conduct infectious disease research on mouse models that require ABSL3 conditions in support of the scientific community and users of the MMRRC resource. This proposal directly addresses a number of the stated objectives of this special NIH call. The parent peer-reviewed NIH funded grant (U42OD012210) has been competitively renewed (as of January 1, 2020) for 5 years. A budget of $482,305 direct costs ($485,622 total costs) requested for the remaining months of the current grant year (until January 31, 2022) is less than half the annual total direct cost budget of the parent grant. If funded by this supplement, the impact of the proposed experiments will be to add critically important and urgently needed new capabilities and capacities for studies of SARS-CoV-2 and related viruses and treatment and prophylactic strategies relevant to human disease, especially research to investigate and treat the long-term health consequences of COVID-19, and to understand and respond to new SARS- CoV-2 variants.",2021,2025,N/A,485622,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,1999 +C15180,1R41AI162575-01A1,Rapid Genetic Fingerprinting of SARS-Cov-2 Variants,"ABSTRACT Since the pandemic spread, SARS-Cov-2 split by mutation into several dozens of closely related clonal groups (phylogenetic clades) that continue to circulate around the globe and form sub-clades from within. Rapid point- of-care/-need capturing of the populational diversification of SARS-Cov-2 is essential for real-time surveillance, fast containment measures and personalized treatment of the patients. The goal is to develop a rapid (<2h) and simple (CLIA-moderate complexity) test for detection and high-resolution genetic fingerprinting of SARS- Cov-2 virus variants (C2F test). The test is expected to resolve a hundred or more of the SARS-Cov-2-types that are most relevant from clinical and/or epidemiological perspectives. The C2F test will be based on a novel approach of Nested Multiplex Reverse Transcription PCR (NMRTP) involving two-step reaction (virus detection and, then, fingerprint determination, both in the same reaction tube) and utilizing common laboratory thermocyclers. The fingerprint will be resolved on 10 capture lines of a lateral flow dipstick creating a binary barcode unique to each SARS-Cov-2-type of interest. First, we will select variable sites across SARS-Cov-2 genomes deposited in public database. SARS-Cov-2 genomes will be subjected to cladistic analysis to determine the main phylogenetic lineages currently circulating across USA and global regions. We will identify the most informative nucleotide positions as well as sites in SARS-Cov-2 proteins that are hotspots for mutational changes and tend to be targeted in the future. Optimal sets of target markers for genetic fingerprinting will be determined. Second, we will design multiple compatible primers for interrogation of the fingerprinting markers. We will design and test compatibility in multiplex reaction-specific primers for, on the one hand, cDNA synthesis and PCR amplifications of highly-variable regions for step 1 of the C2F test and, on the other hand, PCR amplification of the variable sites within those regions for step 2. For the purpose of primer optimization, we will utilize ~350 of SARS-Cov-2-positive oronasal samples already in hands or, if needed, recombinant synthetic SARS-Cov-2 RNA. Third, we will validate the optimized primer combinations using clinical samples. The selected primer combinations will be validated on SARS-Cov-2 positive clinical samples (e.g. oro-nasal/-pharyngeal swabs) from various patients, progressively collected during the course of study period in Seattle and Washington DC, with up to 300 samples received from each collection site. In parallel, SARS-Cov-2 genetic variants in the clinical samples will be analyzed by whole genome sequencing. Finally, we will optimize the peripheral components of the C2F test to comply with the CLIA-moderate complexity test requirements and, in Phase II, create a comprehensive database of the SARS-Cov-2 variant fingerprints and associated epidemiological and, when available, clinical metadata (e.g. asymptomatic carriage, mild or severe form of symptomatic infections, etc).",2021,2022,N/A,299200,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2021 +C15181,3U54CA132384-10S4,Increasing COVID-19 vaccine uptake through a patient navigation intervention among underserved populations,"PROJECT SUMMARY (of funded award) The novel SARS-CoV-2 continues to spread in the United States, with almost 5 million confirmed cases of and over 150,000 deaths. Given observed disparities in morbidity, hospitalization, and mortality across race, ethnicity, and socioeconomic status, there is a great need to increase testing access and uptake with rapid return of test results. We propose a community health worker (CHW)-led approach to facilitate COVID-19 testing for underserved populations, with a focus on increasing testing access, uptake, and impact among Latinx, African American, Filipino, and immigrant communities using different testing implementation strategies. Our project will utilize existing COVID-19 contact tracing and community partner infrastructure to reach individuals aged 12 and above exposed or at high-risk of COVID-19 exposure who may be less able to test. We will use a cluster randomized crossover trial to test mobile and home-based testing strategies for increasing testing uptake among contacts, referred high-risk friends and family, and the broader community. Our specific aims are to: 1) Implement COVID-19 testing integrated into community health worker contact tracing home visits and compare the subsequent uptake of testing for referred high-risk friends and family in a mobile testing vs. home-based testing approach; 2) Using a community-led rapid cycle research process, identify effective strategies to promote uptake of COVID-19 testing through mobile/pop-up testing for Latinx, African American, Filipino, and immigrant populations exposed or at high risk of exposure to COVID-19 who are not accessing testing; 3) Gather CHW and community insights to establish best practices for future scale-up and sustainability. We expect to test over 40,000 individuals through these efforts. The project will contribute to health disparity reductions in COVID-19 morbidity and mortality and produce high impact through the our core strengths in drawing on local knowledge, the team's existing community partnerships, use of culturally-competent community healthcare workers, point-of-care rapid and inexpensive testing, and the use of real-time geospatial data from our contact tracing program to prioritize locations for mobile pop-up testing. Our focus on underserved populations with high COVID-19 exposures without prior testing access will inform both future testing and vaccination efforts.",2021,2022,N/A,299098,Human Populations,Asian | Black | Other,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2021 +C15182,1R44OD031437-01,Wirelessly controlled BSL3 vivarium system for automated microdosing in studies of infectious diseases,"Project Summary Infectious diseases are caused by micro-organisms, such as bacteria, protozoa, viruses or fungi, which can be transferred through direct or indirect human contact. A viral infection occurs when a host's body is invaded by pathogenic viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 and the current pandemic. This pandemic is the greatest public health challenge since the 1918 influenza pandemic and the biggest threat to destabilizing the global economy since World War II. As viruses tend to mutate quicker than other pathogenic agents (and thus newer strains emerge time and again), continuous research is required to combat infectious agents. For preclinical research, the most frequently used animal models are mice and rats. They offer an optimal combination of genetic proximity to humans, cost for breeding and colony maintenance possibilities due to their small size. Mice offer the broadest spectrum of available models. Rats are the second most frequently used mammal animal model. In fact, several SARS-CoV- 2 researchers are turning to rats. They are no more susceptible to COVID-19 than mice, but their larger size is an advantage, as, for example, researchers often want to do repetitive bleeding in an experiment but cannot do that with mice. Furthermore, as vaccine studies often assess how different doses affect antibody responses over several days, most toxicology studies of drugs also start in rat. To achieve intermittent infusions in most non-infectious disease research, the current prevailing administration modes for small animal research are manual (oral, intravenous, intraperitoneal, subcutaneous) requiring repeated handling by trained technicians. However, infectious disease researchers desire the least number of touchpoints possible with their infected animals, especially when sharp needles are involved The proposed FluidSync BSL3 system may aid the discovery of new treatments for COVID-19 by enabling candidate drugs to be administered to model animals infected with SARS-CoV-2 while minimizing investigator contact. It may also be used in the development of vaccines and antibodies. The system builds on the first and only wireless and tether-free administration system that can be used in animals as small as mice. The new system will have new capabilities including i) a medical-grade primary battery and ii) a programmable system-on-chip including Bluetooth telemetry transceiver, processor and memory. Ultimately, the FluidSync BSL3 microinfusion system would enable an intelligent instrumented vivarium system that addresses many BSL3 user requirements with benefits including increased productivity, reduced researcher exposure to potentially toxic drugs and disease vectors, ease of management of large-scale animal studies, and minimized animal handling to reduce white coat effects.",2021,2023,N/A,1273102,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +C15183,1R01MD016372-01,Behavioral and Social Science Research to Optimize SARS-CoV-2 Protective Vaccine Uptake in Racial Minority Communities with High Rates of COVID-19,"ABSTRACT Intensive efforts are underway to develop a vaccine protective against SARS-CoV-2 infection, and hope is high that a safe and effective vaccine will soon be available. However, development of a vaccine does not ensure its uptake on the scale needed to bring COVID-19 under control. In the United States, communities of color are disproportionately burdened by COVID-19 diagnosis, serious illness, and death. However, experience in areas such as influenza vaccination portends that COVID-19 vaccine uptake will be lower in African American communities hard-hit by the disease. Racial disparities in influenza vaccination have been linked to individual factors (including low vaccine awareness, medical mistrust, fears and vaccine skepticism); structural barriers (such as not having an accessible primary health care provider); peer group norms that do not sufficiently support getting vaccinated; and social, economic, and life stressors that contribute to many health inequities. Similar but also unique factors are likely to undermine acceptance of COVID-19 vaccination in racial minority communities. Community-engaged research must be undertaken now-and at a point before a vaccine is widely available-to understand and address community concerns and to develop strategies to prevent racial disparities in COVID-19 vaccination uptake. The planned research will be undertaken in Milwaukee by a team of behavioral and social scientists in a collaboration with an established federally qualified community health center serving low-income inner-city residents. The research will use mixed methods to identify minority community concerns regarding COVID-19 vaccination; to determine factors that influence strength of community members' intentions to vaccinate; and to pilot test and establish the feasibility and acceptability of a virtually-delivered intervention that engages community social influencers to address vaccine concerns and endorse vaccine benefits within their social networks. The work will be undertaken in an accelerated manner in three distinct but interrelated phases, all with samples diverse in age and gender: (1) focus groups conducted with 160 African American inner-city community members to elicit COVID-19 vaccine beliefs; perceived risks, benefits, and norms; and factors that would impede or facilitate vaccination; (2) an online quantitative survey study that will enroll 700 community members from zip codes with greatest SARS-CoV-2 rates and will measure respondents' intentions to vaccinate and test the influence on those intentions of theory-based predictors including perceived COVID-19 threat; perceived vaccination benefits, barriers, and self-efficacy, as well as identifying preferred settings for vaccination; and (3) a feasibility and acceptability pilot test of a virtually-delivered intervention that trains and enlists personally-known and trusted neighborhood social influencers to address the COVID-19 vaccination concerns of their friends, family members, neighbors, coworkers, and social media followers, and that supports informed decisions about vaccination. This research will characterize vaccine concerns and identify strategies that can optimize vaccine uptake in racial minority communities vulnerable to COVID-19.",2021,2024,N/A,639327,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15184,1R01AI160052-01A1,De Novo Design of Minibinder Antagonists for COVID-19 and Future Pandemics,"PROJECT SUMMARY One of the most pressing public health priorities for the COVID-19 pandemic is the development of an effective and inexpensive therapeutic. The long-term goal of this proposal is to develop such COVID-19 treatments, as well as the methods needed to rapidly create such molecules as soon as any new pathogen is identified. The central hypothesis is that computational design can be used to quickly create proteins with potent antiviral activity and others that suppress ""cytokine storms"" associated with advanced infection. Such countermeasures, if rapidly developed and deployed, could save millions of lives during an outbreak until vaccines are developed. The specific aims are to: 1) overcome current limitations in the discovery and development of protein therapeutics by creating methods for the de novo design of hyper-stable miniproteins that bind tightly to vulnerable binding sites on the SARS-CoV-2 Spike glycoprotein, including the receptor binding domain (RBD) of the ACE-2 cellular receptor and the fusion peptide region; 2) Enhance the avidity of such anti-Spike minibinders through genetic fusion of multiple copies, or through rational design of higher-order oligomers to create drug compounds that are less prone to viral mutagenic escape; 3) Apply the same minibinder design pipeline to create cytokine receptor antagonists of key cytokines IL-6 and IL-1β likely involved in acute respiratory distress syndrome (ADRS) associated with COVID-19 mortality; 4) Assess the efficacy of antiviral and anti-interleukin minibinders by several routes of delivery (intravenous, intranasal and subcutaneous) in rodent models of COVID-19 and assess immunogenicity in order to identify those designs best suited for further preclinical development. As proof of principle, the first anti-Spike minibinders have already been designed, were found to bind to SARS-CoV-2 Spike RBD, and were found to neutralize live virus with activities rivaling the most potent known antibodies. This proposal is innovative because it seeks to apply powerful emerging methods in the computational design of new protein therapeutics to the COVID-19 pandemic. The proposal is significant because it would be the first example of computational protein design yielding potent and entirely de novo antiviral and anti-inflammatory therapeutics for an active pandemic. Ultimately, rapid minibinder design methods have the potential to generate treatments for future pandemics, as well as for many other common and neglected diseases and conditions.",2021,2026,N/A,723634,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15185,5R01AI157155-02,Human antibody-based countermeasures against the Coronavirus SARS-CoV-2,"Project Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus that was first isolated in Wuhan China in December, 2019. SARS-CoV-2 is the cause of coronavirus disease 2019 (COVID-19), which is now a pandemic and has caused more than 1.3 million confirmed cases and 72,000 deaths, with an estimated case fatality rate of 4%, with substantially higher death rates (~15%) in the elderly or immunocompromised. Virtually all countries and territories have reported cases, with major epidemics in China, Italy, Spain, France, Germany, Iran, and the United States. SARS-CoV-2 is thought to be of zoonotic origin, most likely bats, and is about 75% identical to the original SARS-CoV. Most cases are spread by direct human-to- human transmission, with community transmission in asymptomatic individuals described. Currently, no countermeasures are licensed for human use. The development, characterization, and ultimately deployment of an antibody-based treatment against SARS-CoV-2 could prevent substantial morbidity and mortality, and possibly mitigate its epidemic spread. This interactive multi-PI proposal leverages complementary expertise in the Diamond, Crowe, and Baric laboratories to rapidly develop highly neutralizing and therapeutic human monoclonal antibodies (mAbs) against SARS-CoV-2 for immediate use in humans. To achieve this goal, we will generate and interrogate human mAbs against SARS-CoV-2 that are obtained from multiple convalescent subjects. We will identify potently neutralizing mAbs and optimize them for affinity by selecting naturally occurring somatic variants identified by repertoire sequencing and sibling analysis and Fc effector functions. Protective activity of top candidate coronavirus mAbs will be tested in newly-generated and optimized mouse models of SARS-CoV-2 infection, including those expressing human ACE2 receptors (hACE2). To define correlates of protection, we will use chimeric viruses, shotgun mutagenesis, and neutralization escape to identify the epitopes of our most protective mAbs. Our team has extensive experience in the generation, characterization and optimization of antibodies, CoV biology, and animal models of disease and protection. A therapy composed of one to three highly neutralizing mAbs may provide an immediate countermeasure against the pandemic spread of SARS-CoV-2 and help establish correlates of structural and functional humoral protection that ultimately inform vaccine efforts.",2021,2025,N/A,1206220,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C15186,1R01AI166791-01,Novel diagnostic tools and animal model system for study human/animal interface of COVID-19,"The ongoing pandemic of COVID-19 is designated by World Health Organization (WHO) as a Public Health Emergency of International Concern. Similarities among ACE2 receptors predict that there are several animals could function as reservoirs for the virus. Recent studies by us and others identified felid animals, including domestic cats, tigers and lions as highly susceptible to SARS-CoV-2 infection. These findings cause great concerns on the potential for human to animal and animal to human transmission, along with the virus mutations that appear as the virus goes back and forth between species. One goal of this study is to design and prepare novel reagents and assays for detection and surveillance in animals. A second goal is to develop a feline animal model. Together, these data will be incorporated into models for understanding the risk of animal infection for veterinarians, other animal care professionals, and the general public. Specific Aims are: 1). To generate and characterize specific reagents for use in COVID-19 research and diagnostics; 2). To develop diagnostic assays for detecting COVID-19 virus infection in animals; 3). To establish a feline model to study SARS-CoV-2 pathogenesis; 4). To apply novel diagnostic assays in the surveillance of pets and zoo animal populations. Outcomes of this study will generate a panel of SARS-CoV- 2-specific antibody reagents, diagnostic standards, and assays for rapid detection of SARS-CoV-2 infection in all species of animals. The diagnostic assays will be applied to COVID-19 surveillance networks, which will identify important animal reservoirs. The novel serological assay can also serve as a DIVA test to differentiate between the vaccinated and infected animals (and humans). The feline pathogenesis studies will improve our understanding of viral pathogenic mechanisms, host immune responses, and provide the source of samples for early detection and test validation.",2021,2025,N/A,799280,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Disease models | Animal source and routes of transmission,2021 +C15187,1R01AI167711-01,Immune response to COVID-19 vaccine in HIV infected men and women,"ABSTRACT The CDC recommends that persons living with HIV (PWH) be vaccinated against SARS-CoV-2. However, there are minimal scientific data to support this important public health principle in relation to ongoing immune dysfunction and chronic comorbidities and the persistent HIV reservoir in antiretroviral treated (ART) PWH. We propose that a formal, comprehensive, longitudinal study in a well-characterized cohort of male and female PWH compared to HIV uninfected controls (HUC) is essential to assess the immunogenicity of COVID-19 vaccines in PWH. The MACS-WIHS Combined Cohort Study (MWCCS) is ideal for analyzing the interactive impact of chronic HIV infection on COVID-19 Pfizer and Moderna RNA-based vaccine immune responses to SARS-CoV-2 and the HIV reservoir. In Aim 1, we propose to conduct an in- depth analysis of antibody neutralizing function and B lymphocyte responses in 100 male PWH and 100 female vaccinated PWH, and 25 male and 25 female vaccinated HUC, from the MWCCS. In Aim 2, we will extensively characterize immune cell phenotypes, soluble markers, and functional cellular immune responses to SARS-CoV-2 vaccination in the participants from Aim 1 before and after vaccination. In Aim 3, we will evaluate the effects of COVID-19 vaccine on the persistent HIV reservoir (amount and composition, immune parameters) before and after immunization. Aim 4 applies machine learning approaches on the entire set of features quantified in Aims 1-3 to predict COVID-19 vaccine response outcomes and determine the critical parameters that influence vaccine responses. We believe that this study is unique, important, and critically timely for assessing the scientifically unprecedented, vaccine prevention phase of the COVID-19 pandemic in the context of HIV infection.",2021,2026,N/A,788164,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +C15188,1R01HL159433-01,Mechanistic registry to study whether infection with Corona Virus Disease 2019 (COVID-19) alters atherosclerotic plaque progression,"Project Summary / Abstract The primary objective of the corona virus disease 2019 (COVID-19) (COVID-CT) registry is to determine if infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus which causes COVID-19, results in marked progression of coronary atherosclerotic plaque in patients with previously defined anatomic coronary artery disease (CAD). COVID-19 induces a pro-inflammatory cytokine release and pro- thrombotic processes that we hypothesize will accelerate atherosclerotic plaque progression. Coronary computed tomographic angiography (CCTA) is a robust noninvasive method uniquely capable of measuring angiographic stenosis and quantifying and characterizing atherosclerotic plaque. Our group has extensive experience in large multicenter trials and registries using CCTA to identify key atherosclerotic plaque features associated with progression and major CAD events. Moreover, we propose use of a novel CT marker of coronary artery inflammation - the perivascular fat attenuation index (FAI) - a marker highly predictive of acute CAD events and to assess serial changes in coronary inflammation. COVID-19 is rapidly becoming a leading cause of death with substantial evidence that pre-existing CAD increases risk of serious illness and mortality from COVID-19. By enrolling patients with high risk, atherosclerotic plaque, findings from the COVID-CT registry will inform this link between the inflammatory response sustained during COVID-19 to accelerated atherosclerotic plaque progression. If our hypotheses are confirmed, then clinicians and patients will have clear information that viral infections, such as SARS-CoV-2, alter the inflammatory milieu and accelerate progression of atherosclerosis. Importantly, a connection between COVID- 19 and CAD will broadly impact preventive risk assessment for the ~7 million patients infected with SARS-CoV- 2 and millions more yet to be tested in the United States. To date, evidence is lacking as to whether the COVID-19 results in marked atherosclerotic plaque progression among racially and ethnically diverse patients with CCTA-defined CAD who reside across a socioeconomically- diverse, urban setting. The present proposal constitutes a comprehensive approach assessing the clinical importance of atherosclerotic plaque progression following COVID-19. Currently, the implications of epicardial coronary injury following SARS-CoV-2 infection is unknown. Yet, the inflammatory pathway of atherosclerotic plaque progression is well studied and, as such, our hypotheses are supported by this knowledge base. The proposed COVID-19 registry is poised to provide an improved mechanistic understanding of the role of viral infection on alterations in atherosclerotic plaque.",2021,2025,N/A,1620596,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15189,3P51OD011104-60S2,Post-Acute COVID Sequelae in African Green Monkeys,"PROJECT SUMMARY The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has resulted in global morbidity and mortality of dramatic proportions. Although the development of vaccines has occurred at an extremely rapid pace, significant challenges remain including vaccine hesitancy, the development of new variants, and major new outbreaks within several countries, despite best efforts for vaccine production and deployment. In addition, there is an urgent need to be able to address the post-acute sequelae of COVID-19 (PASC) or long haul COVID. Significant health problems, including neurobehavioral, pulmonary, renal, and cardiovascular abnormalities have been observed in both hospitalized and non-hospitalized patients well beyond the acute phase of infection, where replication competent virus is no longer shed. In studies proposed here, we will establish a model for the investigation of the longer-term effects of SARS-CoV- 2 infection in African green monkeys (AGM) supported by our previous observations during the acute phase of infection. In the context of our research strategy, we will perform clinical, biologic, immunologic, virologic, behavioral, pulmonary (plethysmography) and telemetric studies at baseline and during the course of our studies. The first six weeks of SARS-CoV-2 infection will be investigated within our Regional Biocontainment Laboratory at BSL- 3. At six weeks post-infection, we will evaluate the status of active and transmissible infection to support the safe transfer of animals to a BSL-2+ environment for an additional 12 weeks, where we will study the longer-term consequences of SARS-CoV-2 infection. Necropsies will be performed within BSL-3 as a safety precaution. Considerable anecdotal and survey evidence suggests vaccination of persons with PASC symptoms can be mitigated in whole or in part by the administration of vaccines approved under emergency use authorization. Our studies will investigate the administration of the Pfizer vaccine to animals two days post-infection to determine its potential as a therapeutic vaccine to modulate the acute and post-acute infection phases. We will also evaluate the potential of a Cathepsin-L inhibitor that interferes with cell entry of SARS-CoV-2 infection. Our previous collaborative studies with Selva Therapeutics, Inc, suggests virological and immunologic properties with earlier detection of neutralizing antibodies in AGM. We anticipate the proposed studies may provide urgently needed novel, translatable, and actionable approaches for the modulation of COVID-19 disease in humans.",2021,2022,N/A,499993,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease models",2021 +C15190,1R01AI161008-01A1,Early life B cell responses and inflammation following SARS-CoV-2 infection,"Abstract As of March 2021, SARS-CoV-2 has caused more than 50 million infections and 2 million deaths, constituting an unprecedented pandemic in the modern world. While infected individuals rapidly develop IgG responses against the viral Spike after infection, some studies have indicated that individuals with mild infection generate weaker neutralizing Ab responses compared to those with severe disease. The durability of the immune response following natural infection and its afforded protection against subsequent infections and emerging related variants remain unclear. Interestingly, unlike other respiratory viruses, children are rarely develop severe disease following SARS CoV-2 infection. Antibody responses in hospitalized children and those who developed the multisystem inflammatory syndrome (MIS-C) have been characterized, but, there is a gap in knowledge of the magnitude, quality, durability, and breadth of antibody responses in asymptomatic or mildly symptomatic children, responses that may contribute to making children less susceptible to severe infection compared to adults. Moreover, the possibiltiy of reinfection or infection with a novel variant in previously-infected children is not known, making the possibility of restarting congregate settings for children without a childhood vaccine quite challenging. Our overarching goal is to characterize the kinetics, function, breadth, and durability of humoral immune responses elicited by SARS-CoV-2 infection across the pediatric age spectrum in comparison to that of adults. We hypothesize that pediatric immune responses to SARS-CoV-2 infection is distinct from that of adults, and associates with protection against symptomatic disease and durability of immunity. Using samples from two unique ongoing community studies of SARS-CoV-2 infections in adults and children, we will test our hypothesis through the following aims: 1) Define the similarities and differences in the kinetics, magnitude, specificity, function and durability of SARS-CoV-2-specific Ab responses in children and adults; 2) Investigate the breadth and potency of antibody responses in SARS- CoV-2-infected children against established and predicted variants of SARS-CoV-2; and 3) Define the SARS-CoV-2-specific B cell repertoire and characterize the potency of pediatric SARS CoV-2-specific monoclonal antibodies. These evaluations will identify immune correlates of protection against severe disease and provide insights for immunization strategies towards the long term control of SARS CoV-2 which will likely become an endemic pathogen.",2021,2026,N/A,854272,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility,2021 +C15191,3U01AI138897-04S1,COVID Protection After Transplant (CPAT) Multicenter Adaptive Trial,"Solid organ transplant recipients experience high mortality from COVID-19 due to a combination of immunosuppression and comorbidities. Although SARS-CoV-2 vaccination has been highly effective in the general population, recent studies show that solid organ transplant recipients are less likely to develop protective antibody responses. In addition, long term studies of safety, including immunologic sequela such as rejection, and de novo donor-specific antibody formation are lacking. We propose a Multicenter Randomized Adaptive Design Trial to investigate strategies for CPAT (COVID Protection After Transplant). This trial will build on results from a CPAT Pilot Trial in 200 kidney transplant reipients which will investigate the safety and immunogenicity of 3rd dose of a SARS-CoV-2 mRNA vaccines in recipients who fail to develop high level antibodies after a standard 2 dose series. That trial will identify key correlates of risk and efficacy. This trial will incorporate that data to investigate additional protective strategies including the use of different vaccine platforms and changes in immunosuppression in 800 solid organ transplant recipients with suboptimal anti-spike antibody responses across 15 US transplant centers. This trial will personalize randomization to candidate arms with the highest probability of success using a Bayesian framework. In conjuction, we will perform novel, comprehensive virologic and immunologic mechanistic studies to better understand vaccine-associated immunity over time. Our multidisciplinary team includes experts in Transplant Surgery, Infectious Diseases, Epidemiology, Biostatistics, Pathology, Virology, and Immunology. Our team has experience successfully enrolling and conducting multicenter transplantation trials (U01AI134591, U01AI138897) and will leverage existing infrastructure for operations, data management, analysis, and safety reporting. In summary, this Multicenter Adaptive Design CPAT Trial will determine the immunogenicity and safety of novel SARS-CoV-2 vaccination strategies in 800 transplant recipients across the United States. Important mechanistic studies will further fundamental understanding of development of protective immune responses in this vulnerable population.",2021,2023,N/A,6941821,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Prognostic factors for disease severity | Phase 3 clinical trial | Characterisation of vaccine-induced immunity,2021 +C15193,1R01AI163336-01,Kinetic and structural basis for SARS-CoV-2 RNA-dependent RNA polymerase specificity and inhibition,"Project Summary/Abstract Although there is much hope for an effective vaccine to combat COVID-19, a pressing need remains to develop direct acting antivirals in the event that vaccines fail to provide protective immunity, for the treatment of acute infections, and for future coronavirus strains that might evade existing vaccines. The SARS coronavirus (CoV- 2) RNA-dependent RNA polymerase (RdRp) is an attractive target because inhibitors of viral RNA-dependent polymerases form the cornerstone of antiviral drug combination therapy for successful treatment of HIV and hepatitis C virus infections. Remdesivir, a nucleotide analog developed by Gilead, is already showing promise in clinical trials. The long-term goal of this research is to facilitate the development of more effective, less toxic drugs directed against the SARS CoV-2 RdRp. The rationale for this research is based on prior experience demonstrating that accurate measurements of the kinetics of nucleotide incorporation and excision by the viral polymerase/exonuclease translates directly to understanding viral RNA replication and can guide the design of robust assays to find effective inhibitors. Kinetic analysis will be based on single turnover rapid-kinetic measurements of polymerization to provide definitive results to define the mechanistic basis for nucleotide selectivity. Our working hypothesis is that an effective nucleotide analog can be identified and its therapeutic potential quantified based on analysis of the kinetics of incorporation relative to the kinetics of excision by the proofreading exonuclease. Specifically, the aims of this research are to quantify the kinetics of nucleotide incorporation using single turnover kinetic analysis in order to establish the mechanism and overall fidelity of the RNA replication. Parallel studies will establish the kinetic and mechanistic basis for inhibition for nucleotide analogs. We will also include extensive characterization of the kinetics of the proofreading exonuclease to define the rules governing removal of mismatched base pairs and nucleotide analogs. We will also us cryoEM with samples based on our biochemical knowledge to obtain structures of the polymerase with Remdesivir incorporated and of the RdRp with the exonuclease. These studies are innovative in that they take advantage of the most advanced methods of single turnover kinetic analysis and global data fitting developed by the PI to establish the kinetic and thermodynamic basis for polymerase specificity to reveal the basis for discrimination against nucleotide analogs. No other lab is applying such standards to this important problem. Moreover, this quantitative analysis provides an accurate vector pointing toward more effective inhibitors in structure/activity relationship studies. The work is soundly based the the PI's prior work and on preliminary data explaining the kinetic basis for the effectiveness of Remdesivir in competing with ATP. The proposed research will significantly advance our understanding the mechanism and kinetics of CoV RNA replication and provide a sound quantitative basis to find inhibitors acting directly against viral replication. This research has a strong potential to play a key role in the developing direct acting antiviral drugs to combat SARS CoV-2 and future coronaviruses.",2021,2026,N/A,577840,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15194,1R01AI161374-01,Development and characterization of engineered therapeutic antibodies against SARS-CoV-2,"Project Summary/Abstract This R01 entitled, ""Development and characterization of engineered therapeutic antibodies against SARS-CoV- 2"", builds on our project infrastructure, expertise, and experience in characterizing viral-host factor interactions in negative strand RNA viruses. Since originating in China, SARS-CoV-2 has since rapidly spread and is now a global pandemic. Significant concerns are that humans are immunologically naïve, and there are no available therapies. In the US, the disease has already overwhelmed the healthcare system in some states and have a serious knock-on effect in exacerbating the standard of care for other diseases. At the time of writing, nearly 5 million cases and >160,000 deaths have been attributed to COVID-19. The virus replicates in the lungs and causes a severe respiratory disease, COVID-19, which is fatal in >2% of cases. Neutralizing antibodies (nAbs) generated by natural infection or vaccines is known to control many infections and early studies in the current COVID-19 pandemic, including studies to test convalescent plasma treatments, are promising. These studies highlight the potential significance of nAb-based therapy. While IgG format of nAbs have long been the most extensively used format, early studies, including our own suggest that additional multivalent formats of nAbs may be more effective. This provides an innovative method to develop nAbs while acquiring potential benefits from effective neutralization at lower doses and lower likelihood of the emergence of resistance mutants. SARS-CoV- 2 is a single stranded, non-segmented, enveloped RNA virus. Viral infection requires interaction of the spike glycoprotein receptor binding domain (RBD) to the host receptor ACE2. Here, we will build on newly developed and established approaches that have been optimized through our work other systems to generate antibodies targeting spike and spike RBD using phage display technology and characterize their physical properties. We will engineer antibodies with increased valency and test for potency in in vitro neutralization assays and in vivo efficacy in a mouse model. At the completion, we expect to provide innovative and unique multivalent nAb leads with unique characteristics that will rival the best in class IgG drugs.",2021,2024,N/A,667277,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15195,1R21AI161567-01,T cell modulation of COVID-19 disease,"Project Summary/Abstract The novel coronavirus that emerged in late 2019, termed SARS-CoV-2, quickly spread throughout the world and has, to date, infected millions and killed hundreds of thousands. This virus is shockingly complex in that the majority of infected individuals show few overt symptoms (though some data suggest they may have lasting damage nonetheless) but are largely healthy. In contrast, a small fraction of infected individuals exhibit a range of serious symptoms including pneumonia, acute respiratory distress, clotting disorders, and even death. The mechanisms that underly mild versus severe symptoms are not fully understood but immune mechanisms appear to play a role. Thus, we need to understand the roles of particular immune cells in order to understand the disease and properly treat it. Of particular interest is the role of CD8 T cells (CTL) in disease outcome. In this project we will use the rhesus macaque model of SARS-CoV-2 infection to assess the importance of CTL and other CD8+ cells in disease. In aim 1, we will deplete animals of all cells that express the CD8a molecule, including CTL and NK cells, and assess their ability to clear the virus. In aim 2, we will target only CTL for depletion and likewise assess their importance. In aim 3, we will use cells in the lab to assess how CTL interact with virus infected cells. Together, this project will comprehensively assess the importance of CTL in COVID-19 disease or protection from it.",2021,2023,N/A,255000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2021 +C15196,272201600013C-P00018-9999-13,MICROBIOLOGY AND INFECTIOUS DISEASES BIOLOGICAL RESEARCH REPOSITORY (MID BRR): SARS-CoV-2 VACCINE RESEARCH RELATED ACTIVITIES,"This contract provides unique and quality-assured infectious reagents and resources to the scientific community for use in basic research and product development. The scope of this contract includes the acquisition, authentication, production, preservation, storage, and distribution of research and reference reagents to the research community. These reagents span the pathogens in the Division of Microbiology and Infectious Diseases portfolio, and include the National Institutes of Allergy and Infectious Disease (NIAID) Category A, B and C Priority Pathogens and emerging infectious diseases.",2020,2020,N/A,3008705,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,,,2020 +C15198,1R01AI161348-01,Revising Anti-coronavirus Compounds to Enhance Activity and Optimize Delivery,"Project Summary/Abstract The current outbreak of COVID-19 has had devastating global effects on morbidity and mortality. Currently no vaccine is available and no therapeutic with efficacy against SARS-CoV-2019 have been fully approved by the FDA. Remdesivir, an intravenous drug which inhibits the viral RNA polymerase enzyme, has received an EUA designation by the US FDA. A prodrug of N4-hydroxy-cytidine has recently entered Phase 1 trials. Our goal is to synthesize COVID-19 antivirals that inhibit the viral RNA polymerase and can be used orally or intramuscularly with a special focus on delivering maximal amounts of drug to the lungs. We will synthesize prodrugs of remdesivir and other nucleosides with anti-coronavirus activity using an innovative approach that involves converting them to lipid analogs. Some compounds will focus on oral delivery and others on intramuscular administration. The compounds will be screened in vitro against nonpathogenic and pathogenic coronaviruses including SARS-CoV-2 and their activity compared with the unmodified parent nucleosides. Their pharmacokinetics and toxicity of the most active antivirals will be studied in rats. The active antivirals will be evaluated for exposure to lung versus their unmodified nucleosides. Finally, the clinical and antiviral activity of the most promising compounds will be evaluated in the Syrian Golden hamster model of coronavirus disease.",2021,2024,N/A,766165,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15199,1R01HD107420-01,Longitudinal study of health outcomes and mitigating factors in the aftermath of the COVID pandemic,"ABSTRACT The global pandemic caused by SARS-CoV-2 has already claimed over 2 million lives and caused economic and social disruption on an unprecedented scale. There is growing concern about long-term consequences of the pandemic on physical and mental health outcomes of children, stemming from both the illness and from associated disruptions in the economic, social, and healthcare domains. Our overall goal is to study trajectories of child/adolescent mental health and primary healthcare utilization including immunization, in the aftermath of the COVID-19 pandemic. Our project, located in India, will test key hypotheses about the pandemic's impact on health outcomes, vulnerability to future shocks, and sources of heterogeneity in these relationships. A strategic innovation is to create a new health panel dataset - called the SurvEy of HeAlth Trends (SEHAT), which means ""health"" in Hindi - by leveraging the world's largest household panel data on consumption and economic outcomes in India. The SEHAT data will be a new health module spanning 9 waves from September 2021 - August 2024 to generate timely evidence on the pandemic's impact on trajectories of health outcomes. Our project on three COVID-related stressors: (1) disruptions in economic circumstances, (2) disruptions in the social environment, or (3) exposure to severe COVID illness within family networks. We estimate the association between these stressors and (a) mental health, and (b) rates of immunization and primary healthcare utilization. Our second aim is to examine impact of COVID-related stressors on vulnerability to future shocks. Using 9 waves of panel data over a three-year period, we will examine new economic shocks, such as job or income losses in the household, and their cumulative effects on child health outcomes. Our main hypothesis is that the negative impact of future shocks on child health outcomes will be greater in magnitude among children in households that experienced higher levels of COVID-related stressors compared with children from households with lower levels of these stressors. We will also leverage the large amount of data to examine sources of heterogeneity in COVID impacts on child health outcomes, by factors such as gender, caste, or household composition. Our third aim is to make SEHAT panel dataset publicly available to facilitate research and inform policy. Our study aims to collect health data that can be transformative for research and evidence-based policy. We plan to release descriptive statistics on key indicators immediately after every wave, with accompanying policy briefs. After completion of SEHAT data collection in August 2024, we will publicly release microdata by August 2026, prior to end of the grant period. We will also publish detailed documentation to facilitate analysis using the SEHAT data.",2021,2026,N/A,706889,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,South-East Asia,Data Management and Data Sharing | Gender,,,,India,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Indirect health impacts | Social impacts | Health service delivery,2021 +C15200,3P20GM103436-21S1,KY INBRE NOSI Supplement: Targeted COVID-19 Vaccine Decision Making Support for Sexual and Gender Minorities,"Project Summary/Abstract Since the World Health Organization declared COVID-19 a pandemic, 31.6 million Americans have contracted the SARS-CoV-2 virus and 566,000 have died. Effective and safe COVID-19 vaccines have been developed, tested, and deployed in record time and 219 million vaccine doses have been administered in the US. Racial and ethnic disparities in vaccine uptake have been noted, but data are not yet available for some other disadvantaged groups. Sexual and Gender Minorities (SGMs) are potentially at risk for vaccine hesitancy due to social and historical factors affecting vaccination in general and healthcare access specifically. There is a critical need to understand vaccine attitudes and behaviors among SGMs. Our long-term goal is to reduce potential health disparities in COVID-19 among SGMs. The overall objective is to develop and deploy a decision aid that supports SGM COVID-19 vaccine decision making. Using survey and focus group methods, and following accepted international standards for decision aid development, we will develop a tailored decision aid to reduce vaccine decisional conflict and improve vaccine acceptance. The project's specific aims are to: 1. Generate foundational knowledge of COVID-19 vaccine hesitancy among SGMs. We hypothesize that SGMs overall will be somewhat less accepting of the vaccine than the general population and, among SGMs, there will be subgroups with other vaccine hesitancy risk factors (e.g., race, gender minority identity, political affiliation) who have significantly higher rates of vaccine hesitancy. 2. Produce contextualized understanding of intentions to receive the COVID-19 vaccine. We hypothesize the reasons for vaccine acceptance or hesitancy will differ among SGM subgroups. Focus group discussions with diverse samples of SGMs who are vaccine-hesitant will identify knowledge gaps, misconceptions, perceived barriers, negative attitudes such as stigma and mistrust, and preferences for decision support. The primary outcome will be determining decision support needs for SGM subgroups. 3. Create decision aids to reduce decision conflict and improve acceptance of the COVID-19 vaccine. We will generate a decision aid, or multiple versions of a decision aid, to empower the SGM decision maker to compare options for protection against COVID-19, clarify values, and support efficacy for gathering more information, collaborating with a healthcare partner in the decision-making process, and/or obtaining the COVID-19 vaccine. We hypothesize the tailored decision aids will reduce decision conflict and improve vaccine acceptance.",2021,2024,N/A,253183,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2001 +C15201,1R01DK130386-01,Mechanisms of Kidney Injury in COVID-19,"PROJECT SUMMARY/ABSTRACT The SARS-CoV-2 pandemic has infected millions of individuals in the US and caused hundreds of thousands of deaths. We and others have shown that COVID-19 is also strongly associated with devastating and usually rare kidney pathophysiologies, such as collapsing glomerulopathy (CG). As in HIV infection, CG in COVID-19 patients mostly affects individuals with high-risk APOL1 genotypes, which are more prevalent in Black and some Hispanic patients. To guide treatment, there is a pressing need to understand whether COVID-19 nephropathy is due to direct viral infection or indirect mechanisms, such as cytokines or physiologic disturbances that emanate from the lung infection. Addressing this need has been hampered by poorly validated reagents, and misinterpretation of immunohistochemistry and electron microscopy findings. We have assembled a multi-investigator team to uncover the mechanisms of kidney injury due to SARS-CoV-2 infection. We will bring expert and complementary expertise in anatomic, autopsy and renal pathology, integrative genomic analysis, human kidney organoid systems and mouse immunology. We will use primary human tissue specimens, in vitro human kidney model systems and a new mouse model of COVID-19 to define direct and indirect mechanisms of SARS- CoV-2 associated kidney injury in three specific aims. Aim 1: Using kidney tissue specimens from COVID- 19 patients and controls, we will define the spectrum of kidney manifestations in individuals that have been infected with SARS-CoV-2. We will use immunohistochemistry, in situ hybridization, and proteomics to define SARS-CoV-2 kidney infection in a diverse population. In patients with COVID-19 associated CG, we will define molecular changes of this disease using spatial transcriptomic profiling, and the association with APOL1 status. These studies will define the relationship of SARS-CoV-2 infection to COVID-19 associated kidney diseases and uncover molecular mechanisms that underlie direct and indirect modes of kidney injury. Aim 2: Human kidney organoids provide a physiologically relevant model of SARS-CoV-2 infection. We will define cellular, morphologic and molecular hallmarks of SARS-CoV-2 infection in human kidney organoids and organotypic tissue slices. Using established iPSC cells with APOL1 high-risk alleles, we will determine the impact of APOL1 genotype on infection and inflammatory cytokine induced kidney injury. These studies will establish which kidney cells are capable of being infected by SARS-CoV-2, and kidney cell type specific molecular changes induced by viral infection and inflammatory cytokines. Aim 3: We will use a recently developed mouse adapted SARS-CoV-2 virus to determine the effect of SARS CoV-2 infection on kidney function in vivo. Using newly described BAC- transgenic mice that express human APOL1 G0, G1 or G2 alleles, we will define the influence of human APOL1 high-risk alleles on kidney function and kidney injury during SARS-CoV-2 infection. The successful development of these models will establish a paradigm for investigating viral infection associated kidney injury and leverage mouse genetics to define mechanisms of kidney injury and CG, and well as future therapeutic interventions.",2021,2024,N/A,409186,Animals | Human Populations,Unspecified,Unspecified | Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Disease pathogenesis,2021 +C15202,1I01BX005459-01,COVID-19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19,"COVID19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19 The novel coronavirus (SARS-CoV-2) causes a disease called COVID-19. For many people, COVID-19 has almost no symptoms, yet for others, COVID-19 is particularly dangerous and has high morbidity and mortality rates. People with pre-existing type-2 diabetes and atherosclerotic cardiovascular disease (ASCVD) have twice the risk of SARS-CoV-2 infection and are more likely to have poor outcomes. 70% of patients with ASCVD and elevated troponin die of COVID. We don't know what intrinsic factors contribute to these disparate outcomes. High Density Lipoprotein (HDL) particles play a critical role in the innate immune system and are protective against viral and bacterial infections. HDL particles best are known for their roles protecting from atherosclerotic cardiovascular disease (ASCVD). The cardiovascular protection conferred by HDL is largely mediated by HDL's associated proteins, which comprise about half of HDL's mass. Mechanisms for HDL's protection from ASCVD are shared with mechanisms for HDL's protection from viral infections. These protective properties center around the HDL-associated proteins that mediate its anti-inflammatory and antioxidative functions. The goal of this project is to define how HDL may protect from Sars-CoV-2 infection and limit the inflammatory response to COVID-19 illness. Obesity and type-2 diabetes (DM2) lead to hypertriglyceridemia and metabolic changes that impair HDL's anti-inflammatory and antioxidative functions. We will define if DM2 leads to HDL dysfunction and contributes to severe COVID-19 outcomes. Our overarching hypothesis is that HDL's antiviral properties can limit SARS-CoV-2 infection and that HDL's anti-inflammatory and antioxidative capacity limit the systemic inflammatory response to COVID-19. We have initiated a collaboration with Dr. Malall, an immunology expert running a large trial with COVID-19 patients whose de-identified samples are paired with de-identified EMR outcomes data. In AIM1 we will test the hypothesis that SARS-CoV-2 infection impairs HDL's antioxidative and anti-inflammatory capacities, and that these changes can be predicted by proteomic signatures of HDL. We also have collaboration with Dr. Denison, an expert in coronavirus biology. In AIM2 we will test the hypothesis that HDL can reduce SARS-CoV-2 infectivity of lung epithelial cells, but that COVID-19 impairs HDL's antiviral capacity, which can be improved with Remdesavir treatment. In AIM3 we will test the hypothesis that type-2 diabetes alters the HDL-associated protein networks that limit systemic inflammation with COVID-19 and protect against SARS-CoV-2 infection. Diabetes and cardiovascular disease are among the most prevalent problems among United States Veterans, making Veterans more likely to have poor COVID-19 outcomes. An asset to this project is that we can relate our HDL function and antiviral assays with clinical outcomes. Our studies will define proteomic signatures from HDL that are important for its antiviral effects. We ultimately aim to use HDL-directed therapies like recombinant Apo-A1 peptides to improve COVID outcomes.",2021,2023,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease susceptibility | Disease pathogenesis",2021 +C15203,1R21AI161232-01,Accelerated discovery of cell-active SARS-CoV-2 polymerase inhibitors via molecular dynamic guided screening and optimization,"Project Summary Significance: Worldwide spread of the SARS-CoV-2 virus has resulted in over 20 million confirmed human cases and 730,000 deaths from COVID-19, and cases continue to surge as there is no approved vaccine or other therapeutic modality broadly available to mitigate community spread. The virus has not only impacted human health but has also threatened national security, economic stability, and education. Broad, long term objectives: The research objectives described in this proposal will afford vetted, small molecule non-nucleoside-based inhibitors of the SARS-CoV-2 viral polymerase enzyme that will serve as lead compounds for future development and clinical evaluation targeting COVID-19 disease. Specific Aims/premise: The proposed aims are constructed to evaluate if potent, cell permeable, non-nucleot/side-based inhibitors of the SARS-CoV-2 RNA polymerase can be discovered using an integrated drug discovery pipeline. Specifically, we hypothesize that a highly efficient, dynamic computational screening method will reveal desirable hits that will be validated in antiviral assays to show target engagement and cellular efficacy. Further, medicinal chemistry optimization will tune the activity and property profiles of hits to make them suitable for evaluation in our established COVID-19 K18 hACE2 mouse models. Research design and methods: Aim 1 will identify competitive non-nucleot/side SARS-CoV-2 RdRp inhibitors from a strategically chosen compound collection using an efficient in silico screening approach developed and employed by Drs. Baudry and Smith. The hits will be ranked by binding energies and selected for confirmatory activity in the Jonsson's lab using established cellular SARS-CoV-2 assays, along with secondary assays that validate active site inhibition of the viral polymerase. The Golden lab will lead hit validation efforts and advance hits that meet defined criteria to Aim 2. The latter aim will prioritize and evaluate specific scaffolds by medicinal chemistry optimization (Golden lab), guided by the primary and secondary assays, computational models and tiered ADME and pharmacokinetic analyses, to refine compound activity profiles that are suitable for in vivo efficacy assessments performed in the Jonsson lab.",2021,2023,N/A,442542,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15204,1R35GM141812-01,Structural Dynamics of Translation,"The Central Dogma of molecular biology is that DNA is used to make mRNA, which in turn is used to make proteins. Central to physiology of every live cell, translation of messenger RNA (mRNA) into protein is catalyzed by the ribosome, structurally complex and dynamic macromolecular machine. Dysregulation of translation plays an important role in a number of human diseases including cancer. While some fundamentals of protein synthesis have been revealed, many molecular details of ribosomal translation remain unknown. For example, it is unclear why some mRNAs are translated orders of magnitude more efficiently than the others, and how mRNA structure regulates protein synthesis. My laboratory investigates molecular mechanisms of translation by studying structural dynamics of the ribosome, and the role of mRNA secondary structure in translation regulation. We use single-molecule microscopy and biochemical approaches to address the following questions: (i) How does the small ribosomal subunit move along mRNA in search for the start site for translation initiation in eukaryotes? (ii) How does the intrinsic compactness of mRNA and intramolecular basepairing interactions formed by the 5' and 3' untranslated regions (UTRs) of mRNA regulate the efficiency of protein synthesis in eukaryotes? (iii) How do mRNA stem-loop structures induce ribosome translation pauses, which control expression of a number of proteins in bacteria, eukaryotes and eukaryotic viruses, including Human Immunodeficiency Virus (HIV) and the cause of the COVID-19 pandemic, SARS-CoV-2? (iv) How are structural dynamics of eukaryotic ribosome (in particular, rotational movements between the small and the large ribosomal subunits) converted into the intricate process of protein synthesis? Our studies will substantially contribute to establishing the molecular mechanisms of protein synthesis, and provide the basis for the future development of antiviral and cancer therapies.",2021,2026,N/A,376230,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C15205,1R01HL163814-01,SARS-CoV-2 tropism in the brain and its relationship to COVID-19 pathogenesis,"COVID-19 is a US and global disaster which has led to the deaths of almost a million individuals, including over 203,000 Americans, thus far. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome (SARS)-CoV-2, which was reported to cause severe pneumonia and lethal respiratory failure. Little is known about the disease mechanism of this virus and its disease mechanism. In this application, we propose to test the effects of SARS-CoV-2 on the brain. We will develop multiple cell-type specific mouse models that express the SARS-CoV-2 receptor, human ACE2, in a cell-type specific manner. We will then use a variety of molecular, biochemical, histological and neuroscience approaches to test the brain tropism of SARS-CoV-2 in depth and the effects of that on the central regulation of respiration. This proposal will have a transformative impact on our current understanding of COVID- 19 and its mechanisms of pathogenesis and will uncover important therapeutic targets.",2021,2024,N/A,2615479,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis",2021 +C15206,1R01AI163019-01,Mechanism and Inhibition of SARS-CoV-2 Entry,"The long term goal of this study is to understand how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), enters cells and how to block that process through the use of therapeutics. Like other enveloped viruses, SARS-CoV-2 cell entry begins with engagement at the cell-surface and is completed on release of the viral contents following membrane fusion. During the process of cell entry, the SARS-CoV-2 spike protein (S) engages the cellular receptor, angiotensin converting enzyme (ACE2). Proteolytic activation of S is required to activate the fusion machinery which can be achieved by cell surface or endosomal proteases positing a model of cell surface and endosomal entry routes that depend on engagement of different host-cell molecules that vary among cell types. To interrogate the entry pathway of SARS-CoV-2 we developed a set of unique tools that permit application of single virion imaging approaches to track productive entry routes in an unbiased way and to help identify host factors coopted during viral entry. This imaging is facilitated by the use of a chimeric vesicular stomatitis virus (VSV) in which its glycoprotein gene (G) was replaced with the spike (S) gene of SARS-CoV-2. Inhibition of VSV-SARS-CoV-2 infection with monoclonal antibodies, soluble receptor and small molecule inhibitors correlates closely with inhibition of a clinical isolate of SARS-CoV-2, corroborating that the chimera is an effective BSL2 surrogate to study SARS-CoV-2 S-mediated entry. This permits us to genetically modify a core protein of the VSV ribonucleoprotein core to render the particles visible by fluorescent microscopy. By combining this imaging approach, with genetic, chemical and biological perturbations, we will map the entry routes of VSV-SARS-CoV-2 and then examine the effect of those perturbations on infection of cells with a clinical isolate of SARS-CoV-2. We will use this approach to determine how countermeasures currently in clinical trials including monoclonal antibodies, soluble ACE2, and two small molecule inhibitors apilimod and nafamostat block entry. Using genome-wide loss-of-function screens we will also interrogate the requirements for entry of SARS-CoV-2, under native and perturbed conditions to uncover new host proteins that are coopted during entry as potential additional targets for therapeutic intervention. Successful completion of this work will define the entry pathways that lead to productive SARS-CoV-2 infection, inform the mechanism by which multiple molecules in clinical development interfere with that process and unearth new host factors that are coopted during the entry pathway.",2021,2026,N/A,766721,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C15208,2U19AI116497-06,Human Airway Biomimetics for RSV and Other Respiratory Viruses,"PROJECT SUMMARY - Project 2 Respiratory syncytial virus (RSV) is a major global respiratory pathogen. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented crisis. Respiratory virus infections are often accompanied by gastrointestinal (GI) symptoms, but how respiratory pathogens cause GI disease is not understood. Moreover, a number of vaccines and therapeutics are being developed against these important pathogens, however, the existing models do not recapitulate the human experience. Small animal and non-human primate models fall short of mimicking human disease, and the human RSV challenge model is expensive and raises safety concerns. The requirement for BSL-3 facilities to study SARS-CoV-2 hampers data generation and increases cost. The human endemic CoV-NL63 can serve as a proxy for SARS-CoV-2 because it uses the same host receptor, angiotensin-converting enzyme 2. This project will develop an ex-vivo Human Challenge Airway Model by advancing our current 3-dimensional (3D) nose/lung model for studies on RSV and CoV-NL63 (proxy for SARS-CoV-2) to address the urgent need for a preclinical model that recapitulates the human disease. In collaboration with the Human Biomimetic Scientific Core, we have developed the expertise for isolating stems cells and generating 3D nose and lung organoid lines from nasal wash and bronchoalveolar fluids, respectively. Our internationally recognized expertise in RSV and other respiratory viruses uniquely positions us to develop advanced 3D nose/lung models for dissecting the pathogenesis of RSV (Aim 1), and develop airway and GI platforms with the Engineering Micro-Environment Core (EMEC) to evaluate molecular mechanisms driving the lung-gut axis of respiratory virus disease (Aim 2). We will select donors based on sex and age so that we can comprehensively study the complex interactions of host (age, sex, distinct airway sites, and immune cells) and virus, and the contribution of humoral and cellular immune responses in an HLA-restricted system. We will also evaluate the lung-gut axis by studying the downstream effects of RSV and CoV-NL63 airway infection on the GI tract by either direct (infection) or indirect (inflammation) pathways using lung-gut flow systems. This project is responsive to the RFA by the development of an advanced nose/lung model with increased complexity that includes humoral and cellular immunity, as well as defining novel mechanistic pathways in the lung-gut axis of respiratory virus disease. The global scientific community will benefit immensely from a 3-D nose/lung airway-virus model that recapitulates human virus infection and serves as a platform to evaluate therapeutics and vaccines.",2021,2026,N/A,352938,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2015 +C15209,,The Health and Economic Impacts of COVID-19 and Policy Responses,"Project Summary This project develops, estimates, and simulates a cutting-edge model of the health and economic impacts of the COVID-19 pandemic and policy responses to it. The model has four original features: First, it allows for two-way interactions between infections and economic outcomes. These are important because even though the COVID-19 pandemic is fundamentally a matter of public health, it is essential to account for how the pandemic and the policy responses to it affect the economy and how, in turn, the economic impacts affect health, including mental health. Second, it builds policies into a model that accounts for geosocial spread because the SARS-CoV-2 virus is spread through contact with others and policy decisions in one area affect the rest of the country. Third, it allows for incidence rates that are measured only through imperfect proxies, which is particularly important for modeling the prevalence of the virus early in the pandemic in the U.S. as well as in many parts of the world for the foreseeable future. Lastly, the model accounts for disparate impacts across demographic groups, which is critical given that the pandemic has had dramatically different effects on different demographic groups (e.g., by age, gender, race, ethnicity, and living arrangements). This work extends earlier pilot projects that develop a model with the first and second features. Once complete, the model will make it possible to identify the best sets of economic and health outcomes, including infections and mortality, that could have been achieved and the policies that would have produced to those best-case scenario outcomes. It will make it possible to identify the ways in which actual policies deviated from the best policies. It will also make it possible to rigorously quantify the health and economic costs of deviating from the optimal policies overall and for specific demographic groups. In addition to understanding the ways in which policies and outcomes could have been improved as lessons for future outbreaks and pandemics, the estimates can quantify the cost of vaccination rates stalling beneath herd immunity levels. The model can be applied to different countries and to cross-country analysis, and its features are intended to apply to public health crises more generally, such as the opioid epidemic. The ability to apply the model to other epidemics will allow policy makers to ""compare and contrast"" the impacts of different epidemics as well as the same epidemic in different locations using a common approach. Additionally, the project conducts several less structured analyses that document the health and labor market impacts of the COVID-19 pandemic and the policy responses to it. This work will generate results of interest in their own right as policy makers weigh and measure the efficacy of public health responses, will help identify key phenomena to incorporate into our model, and will help us to ensure that the qualitative simulation results are robust to a range of plausible parameter estimates.",2021,2026,N/A,444628,Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Indirect health impacts | Social impacts | Economic impacts,2021 +C15210,3R01DA050542-03S2,Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV,"Project Summary Infection with Covid-19 has reached pandemic status with more than 125 million confirmed cases and 2.75 million deaths making it one of the most deadliest pandemics in history. It is associated with severe acute respiratory syndrome symptoms with high fatality rates. SARS-CoV-2 infection is initiated when its S-protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor through which it gains entry into the host's cells (Kuba et al., 2005; Walls et al., 2020). ACE2 is highly expressed in the in the lungs and to a lesser degree in other organs, such as the heart, kidneys, and intestines (Bavishi et al., 2020), which explains the increased prevalence of lung infection. An analysis of electronic health record data from more than 73 million patients showed that people with SUDs are at higher risk of contracting and suffering worse consequences from COVID- 19 particularly among African Americans. Those with an opioid use disorder (OUD) were 2.4 times more likely to have COVID-19 than those with cocaine use disorder (1.6 times), alcohol use disorder (1.4 times), and tobacco use disorder (smoking or vaping; 1.3 times). Our recent preliminary data show that chronic opioid treatment in a mouse model of opioid substance abuse resulted in significant increase in the expression ACE2 expression in the lungs and brain of these animals. This data suggests that long term exposure to opioids by increasing ACE2 expression in the lung will increase the susceptibility to COVID 19 infection and its expression in the brain suggests high likely hood of neuro-invasiveness. In this supplement we will test the hypothesis that substance use disorders with opioids will increase the risk for COVID 19 infection in the lung and will be associated with neuropathological consequence as a consequence of increased ACE2 expression in brain cells. In Aim 1: We will investigate the expression of ACE2 in small intestine, lung and brain cells in both male and female mice that are chronically treated with morphine. We will further investigate if substance abuse in context of HIV further exacerbates infection and disease progression. In Aim 2; we will investigate using a humanized mouse model where the murine ACE2 receptor is knocked in, the infectivity of the SARS-CoV2 Spike Protein- Pseudotyped GFP using both in vitro and in vivo target cells. In Aim 3 we will investigate the role of the gut microbiome in modulating ACE2 expression levels in the small intestine, lung and brain.",2021,2023,N/A,153500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2021 +C15212,3R01HD098178-03S1,Patient navigation to improve outcomes among low-income women in the postpartum period,"PROJECT SUMMARY Pregnancy is a critical window of opportunity for preventive health interventions, including vaccines. Yet, vaccine hesitancy is a known global phenomenon. Uptake of the currently recommended vaccines in pregnancy (influenza and tetanus, diphtheria, and pertussis [TDaP]) is suboptimal, with only 50% of individuals receiving recommended vaccines. Disparities in vaccine uptake exist, yet this issue has not been thoroughly investigated from the patient perspective. Little is known about the perspectives of pregnant women who identify as racial or ethnic minorities or pregnant women living with HIV (WLHIV), both of whom are underrepresented and understudied populations who are at greater risk of complications from conditions such as influenza. Additionally, the COVID-19 pandemic and introduction of a novel vaccine to health care presents an urgent need to understand factors driving vaccination uptake, particularly in vulnerable populations such as racial and ethnic minority pregnant and postpartum women and WLHIV. Early data suggest that pregnant women and immunocompromised people - such as those living with HIV - are at increased risk of morbidity and mortality from COVID-19. Understanding the evolving perspectives of these populations will inform educational and counseling strategies to enhance vaccination uptake in pregnancy and reduce vaccination disparities. Aim 1 will assess the experiences and preferences of racial and ethnic minority pregnant and postpartum WLHIV and HIV-seronegative women with regard to standard of care vaccines during pregnancy. Individual interviews will address perceptions, experiences, and decisions surrounding routine vaccinations during pregnancy, including issues of trust, access, and knowledge. Analyses will additionally compare perspectives on routine vaccines that may differ by HIV status. Aim 2 will examine the perspectives of this population on the novel COVID-19 vaccine. We will explore motivations and sociocultural underpinnings that may clarify the concerns, beliefs, and experiences surrounding COVID-19 vaccination in pregnancy. We will additionally compare the perspectives of women with and without HIV, and we will analyze differences in attitudes for the COVID-19 vaccine versus standard of care vaccines. To accomplish these aims, we will recruit 40 pregnant or recently postpartum women in partnership with the NICHD-funded Navigating New Motherhood 2 study and the Northwestern Memorial Hospital Women's Infectious Diseases Program. Women with and without HIV will be demographically similar in order to focus on a diverse population of understudied women who are largely low- income and from a racial or ethnic minority. This proposal aims to fill an unmet need for a systematic, in-depth, and unbiased evaluation of the attitudes and preferences of understudied populations of women regarding routine and novel vaccinations during pregnancy. This project directly aligns with the Trans-NIH Strategic Plan for Women's Health Research goals and the aims will address intersections of social determinants of health in diverse populations of women.",2021,2024,N/A,234050,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15213,1R43HL156706-01,Acute Inhibition of TAK1 as a Means to Control COVID-19 Pulmonary Hyperinflammation,"PROJECT SUMMARY/ABSTRACT The recent pandemic of novel coronavirus, COVID-19, has had a devastating effect on the health and well-being of individuals across the globe, including over 3.1 million confirmed infected so far, and a monumental impact on global healthcare systems and economies at large. In the US, over 1,000,000 cases have been confirmed to date, including over 60,000 deaths, and some studies estimate that COVID-19 could cost the US healthcare system $556 billion over the next two years. There are currently no approved treatments for COVID-19, and many current efforts are expectedly targeting the viral mechanisms of disease. However, evidence from COVID- 19 patients has identified hyperinflammation as a major contributor to disease progression and outcomes, and reduction of hyperinflammatory mediators such as TNF, IL-1 and IL-6 has become a novel therapeutic axis for the treatment of COVID-19 patients. Thus, various branded anti-cytokine immunomodulators (e.g., anti-IL-1 and anti-IL-6 biologics) are currently undergoing clinical trials to treat complications of COVID-19 disease such as acute respiratory distress syndrome (ARDS), cytokine release syndrome, and pneumonia. However, all of these therapeutics remove all target cytokine expression, dampening immune-viral detection leading to disease progression. Therefore, there exists an unmet need for an orally bioavailable small molecule therapeutic that can taper inflammatory cytokines to normal levels in an active COVID-19 infection. Our preclinical work has identified TGFβ-activated kinase 1 (TAK1), as a key signaling element within the TNF-mediated proinflammatory response pathway. Given recent clinical data identifying TNF as the primary player in the initiation of the COVID-19 induced cytokine storm, we posit that TAK1 can be targeted to prevent or greatly reduce pulmonary hyperinflammation seen in COVID-19 patients. Our recent discovery of the takinib scaffold and subsequent medicinal chemistry efforts have led to the development of the first orally bioavailable, highly selective and potent (IC50 ~2.5nM) inhibitor of TAK1, HS-276. To obtain proof-of-concept for development of TAK1 as target for COVID-19 induced ARDS, we propose the following Specific Aims: Aim 1 - Establish the therapeutic efficacy of HS-276 to reduce inflammation in the LPS-induced pulmonary inflammatory model. Milestone: Define the therapeutic window of HS-276 in the LPS-induced pulmonary inflammatory model. Aim 2 - Evaluate the in vitro and in vivo effects of TAK1 inhibition with HS-276 in response to COVID-19 spike protein (S-protein) challenge. Milestone: Establish that HS-276 blocks S-protein induced TNF expression by ≥50% compared to vehicle-treated in vitro. Aim 3 - Determine the efficacy of HS-276 to reduce viral-induced ARDS in a SARS-CoV-2 model. Milestone: Expand preclinical indication/efficacy data of HS-276 to treat viral induced pulmonary hyperinflammation. Achieving the Specific Aims above will provide the necessary data for us to pursue a Phase II NIH SBIR application to fund pre-IND-enabling studies en route to IND-enabling studies.",2021,2023,N/A,309288,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15214,1R01DK130414-01,Intestinal organoid modeling of SARS-CoV-2-stimulated innate and adaptive immunity,"ABSTRACT The COVID-19 pandemic, engendered by the novel coronavirus SARS-CoV-2, is a grave threat to public health, with lung infection and respiratory failure. However, the intestine is also targeted by SARS-CoV-2, as many patients present with GI symptoms and the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is abundantly expressed by intestinal epithelium. COVID-19 mortality is strongly associated with systemic inflammation as in ""cytokine storm"", fostering attempts at therapeutic immunomodulation, and raising a critical need for in vitro human systems modeling SARS-CoV-2-induced immune cell interactions with intestinal epithelium. Conventional 3D organoid cultures (""enteroids"") allow intestinal epithelial SARS-CoV-2 infection but unfortunately omit immune cells. Here we generate a holistic intestinal in vitro model of SARS-CoV-2 infection using air-liquid interface (ALI) organoids containing both epithelium and infiltrating immune cells en bloc without artificial reconstitution. The complex intestinal immune system of ALI intestinal organoids contains various innate and adaptive immune cells, highly diverse T cell receptor (TCR) and B cell receptor (BCR) repertoire, and plasma B cell-derived antibody transcripts. Importantly, immune components in these ALI organoids respond efficiently to epithelial damage and ALI intestinal organoids are highly susceptible to bacterial and viral infections. Here, we utilize this unique ALI organoid technology with integrated immune components to explore sequelae of SARS-CoV-2 infection. Aim 1 establishes and optimizes BSL3 SARS-CoV-2 infection of ALI intestinal organoids, exploiting a novel eversion method to relocate the apical aspect of ACE2-expressing cells to the external surface, allowing survey of SARS-CoV-2 infection of different regions of small intestine and colon. The time course of tissue-resident SARS-CoV-2-induced cross-talk between intestinal epithelium and immune cells is unknown, as hindered by lack of human experimental systems. Thus, Aim 2 performs a scRNA- seq and CyTOF study of SARS-CoV-2-induced immune responses within ALI organoids to (1) create a network model of the temporal propagation of immunity and bidirectional communication between epithelium and immune cells and (2) perform therapeutic testing against nodal vulnerabilities, correlating against clinical status (naïve, convalescent, immunized, cross-reactive coronavirus). Current epithelial organoid systems also do not allow study of adaptive immunity. Aim 3 thus recapitulates SARS-CoV-2 adaptive immune responses by co-culturing ALI intestinal organoids with newly developed human lymph node organoids. Within such SARS-CoV-2-infected co-cultures we correlate adaptive immune responses with clinical status including prior cross-reactive coronavirus infection and SARS-CoV-2 naïve, convalescent and ultimately immunized states. Overall, we leverage collaboration from Mark Davis (human LN culture) and Catherine Blish and Scott Boyd (SARS-CoV-2) to create human in vitro systems modeling SARS-CoV-2-induced innate and adaptive immunity, with relevance for pathogenesis investigations and therapeutics testing.",2021,2024,N/A,393625,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Disease models | Pre-clinical studies,2021 +C15215,3R21ES032762-02S1,The External Exposome and COVID-19 Severity among Individuals with Alzheimer's Disease and Related Dementias,"PROJECT SUMMARY The 2019 novel coronavirus disease (COVID-19) is now a global pandemic with severe consequences. Individuals with Alzheimer's disease and related dementias (ADRD) are at a higher risk of contracting COVID- 19 and experiencing severe COVID-19. However, risk factors for COVID-19 severity among individuals with ADRD beyond older age and comorbidities remain largely undefined, and the ability to predict COVID-19 severity among ADRD patients is limited. There are large overlaps between the currently known risk factors of severe COVID-19 and the health conditions that are affected by environmental exposures, and emerging evidence suggested that long-term environmental exposures may be important determinants of COVID-19 severity. Our current R21 (1R21ES032762) was set to identify novel environmental exposures associated with COVID-19 severity considering the totality of the external environment (or the external exposome). Compared with the general population, individuals with ADRD are substantially different in their individual characteristics and environmental exposure profiles. Therefore, a more focused study on the relationships between environmental exposures and COVID-19 severity among ADRD individuals is needed. The rise of real-world data (RWD) creates the perfect opportunity to create a synthetic COVID-19 cohort of individuals with ADRD at the scale needed to understand the full-spectrum of COVID-19 outcomes among individuals with ADRD. Nevertheless, there are two key barriers: (1) the lack of a consensus on methods for examining the external exposome-health associations, and (2) the lack of a pipeline to accurately identify ADRD patients from RWD and extract important risk factors that are only available in unstructured clinical notes. Expanding our parent award on the external exposome and COVID-19 severity to focus on individuals with ADRD, we aim to fill these important gaps to: (1) create a synthetic longitudinal COVID-19 cohort of individuals with ADRD, (2) systematically evaluate statistical methods for external exposome-wide association study (ExWAS), specifically for COVID-19 outcomes among ADRD patients, and (3) through an external ExWAS, identify external exposome factors associated with COVID-19 severity and then develop predictive models of COVID-19 severity among individuals with ADRD. This study builds upon our continuous work on the external exposome and OneFlorida - a repository of RWD with linked electronic health records, claims, and vital statistics data that covers > 60% of Floridians. This study will generate: (1) a large longitudinal COVID-19 cohort of individuals with ADRD, (2) standardized state-of-the-art statistical methods to conduct external ExWAS, and (3) novel external exposome factors associated with COVID-19 severity and predictive models of ADRD patients at high- risk of severe COVID-19. Our approach can be scaled up through PCORnet to create a national cohort and expanded to examine COVID-19's long-term effects among individuals with ADRD in future studies.",2021,2022,N/A,183099,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C15216,1R21AI164088-01,The Development of Reversible Covalent PROTAC Technology as a New Anti-COVID-19 Strategy,"PROJECT SUMMARY/ABSTRACT The current COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. However, to date, no effective targeted drug or vaccine has been identified yet. Finding effective targeted treatment options is of paramount importance. SARS-CoV-2 is an enveloped, positive-sensed RNA virus. Main protease (Mpro), a cysteine protease, is essential for viral replication and pathogenesis which represents an attractive target for the development of antiviral drugs against SARS-CoV-2. One of the traditional antiviral strategies is to develop high- affinity ligands that bind directly to viral proteins and inhibit their functions like SARS-CoV-2 Mpro (SC2Mpro). However, these occupancy-driven inhibitors may lead to several potential problems such as off-target toxicity, dose-limiting toxicity, and drug resistance. Thus, there is an urgent need for new antiviral strategies that can address these challenges by exploiting alternative mechanisms to combat existing CoV pathogens like SARS- CoV-2. Proteolytic targeting chimaera (PROTAC) is an emerging technology for targeted protein degradation in drug discovery. PROTACs are event-driven bifunctional small molecules that simultaneously engage an E3 ubiquitin ligase and a target protein to facilitate the formation of a ternary complex, leading to the ubiquitination and ultimate degradation of the target protein. PROTACs have many potential advantages compared to traditional occupancy-based inhibitors, including (i) catalytic nature to allow for sub-stoichiometric activity, (ii) enhanced target selectivity, (iii) high barrier to resistance; and (iv) abrogating all functions of the target protein and its downstream proteins. On this basis, this proposal provides an innovative anti-CoV strategy: reversible covalent PROTACs by combination of the advantages of ultra-potent reversible covalent SC2Mpro inhibitors and event-driven PROTAC technology. The overall goal is to validate degradation of SC2Mpro as a new strategy for developing COVID-19 drugs with improved selectivity and efficacy. The current proposal is built upon the preliminary work on the discovery of several potent reversible covalent SC2Mpro inhibitors (lowest IC50 < 10 nM) and one small-molecule SC2Mpro PROTAC degrader. Encouraged by these exciting preliminary studies, the goal will be achieved by pursuing the following aims: (1) the development of cellular systems to evaluate degradation of SC2Mpro; (2) the development of various potent reversible covalent anti-CoV PROTACs targeting SC2Mpro; (3) the exploration of the relationship between SC2Mpro degradation potencies and anti-SARS-CoV-2 activities of reversible covalent anti-CoV PROTACs. The successful completion of the proposed study will not only lead to potent anti-CoV PROTACs with good drug-like properties that can be potentially advanced to pre-clinical evaluation for treating COVID-19, but also will provide a proof-of-concept study for more broadly developing anti- CoV PROTACs against various coronaviruses.",2021,2023,N/A,221910,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15217,3U01AI151758-02S1,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","Project Summary/Abstract Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) has rapidly spread across the world. As of June, 2021, over 171 million laboratory-confirmed cases and greater than 3.68 million deaths have been reported globally. This increase in cases has been associated with emergence of new variants which have increased transmissibility and severity. While Southeast Asia kept COVID-19 cases under relative control in 2020. In 2021, SARS-CoV-2 began to spread rapidly and caused continuing outbreaks in the region. In Africa, the genomic surveillance gap, combined with very fragile health systems with limited management capacities, exposes the continent to possible new COVID-19 waves that could prove to be much more severe on the continent, where vaccination clearly remains at a very timid stage. The overall goal of the project is to increase sequencing capacity and add to the depth of sequencing knowledge available in South East Asia and African countries with 4 Specific Aims. 1)To increase sequencing numbers for samples from certain regions. We will focus on samples from land borders with Thailand and Vietnam and community transmission in Cambodia stemming from the February 20th ""event."" These sequences will help to understand community transmission within Cambodia. In Africa, we will increase sequencing numbers from samples from African countries with very low sequencing coverage including Mali, Burkina Faso, Guinea, Côte d'Ivoire, Guinea-Bissau, Niger, Cabo-Verde, Mauritania, Tunisia, Madagascar, Cameroon, Equatorial Guinea and Central Africa Republic. We will confirm known variants of concern as well as detection of potential local new variants. 2)To increase sequencing numbers for samples from patients with atypical profiles. We will systematically collect data at epidemiological level for demographical data, clinical symptoms, COVID-19 vaccination status, history of COVID-19 in relation with patients. We will focus on re-infected patient samples, severe COVID-19 cases and post-vaccinated SARS-CoV-2 infected patients. 3) To monitor introduction and dissemination of known VOCs using molecular sub-typing tools. We will help participating countries building up molecular capacities to subtype known variants. 4) Identify viral genetic determinants of high transmissibility and disease severity. Sequences from severe cases will be analyzed in comparison to the sequences from the randomly selected group to identify viral genetic signatures associated to disease severity. Regarding the transmissibility, we will rely on circulation dynamics of the detected variants in each country as well as in all countries. Overall, the studies outlined in this proposal will rapidly add essential sequence data needed regarding COVID-19 cases in lower-middle income, least-developed countries. They will provide the basis for further study on inter-/intra-host variant emergence and vaccine escape in a unique population from a least-developed country in an understudied, but vitally important, region of the world.",2021,2022,N/A,454536,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Africa | South-East Asia | Western Pacific,Data Management and Data Sharing,,,,Thailand | Viet Nam | Cambodia | Mali | Burkina Faso | Guinea | Cote d'Ivoire | Guinea-Bissau | Niger | Cabo Verde | Mauritania | Tunisia | Madagascar | Cameroon | Equatorial Guinea | Central African Republic,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen genomics, mutations and adaptations | Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity",2021 +C15218,1R01DE031927-01,Development of a handheld rapid air sensing system to monitor and quantify SARS-CoV-2 in aerosols in real-time,"Project Summary The ability to rapidly monitor SARS-CoV-2 in aerosol-drop particles <5 μm in size that evaporate into droplet nuclei and become suspended in air-at the point of presentation is critical to managing the risk of infection by airborne transmission as people return to their communities, workplaces, and schools during the COVID-19 pandemic. However, current enzyme-based methods lack sensitivity, speed, simplicity, and require lab equipment-hence, lack the capability for real-time point-of-presentation (POP) monitoring. In the absence of a real-time POP monitoring capability, SARS-CoV-2 transmission remains poorly understood. In this application, a multidisciplinary research approach that integrates innovations in rapid-kinetic chemical auto-ligation, non- enzymatic isothermal signal amplification, solid-state electronics, and biophotonics is proposed to enable the development of a novel air monitoring system (AMS) that detects and quantifies aerosolized SARS-CoV-2 at the point of presentation in real-time. Recent advances in viral culturing protocols, air sampling technology, and single-photon detection capability will provide the framework for a collaborative research endeavor to establish a new paradigm to address the knowledge gap between the spread of COVID-19 and SARS-CoV-2 aerosol transmission. Therefore, the proposal is aimed at transforming the way COVID-19 is currently researched by providing a tool to enable unparalleled studies that will significantly advance the current knowledgebase. These transformative studies could ultimately guide a new field of investigations that lead to a better understanding of COVID-19 spread, such as viral exposure vs. risk, viral decay rate vs. infectivity, and viral load vs. infectious dose in SARS-CoV-2 airborne transmission. At a minimum, the proposed three research objectives will provide a basic understanding of COVID-19 aerosol transmission. Firstly, current air sampling systems use a multi-step workflow that takes several hours to complete and requires lab equipment, reagents, and significant hands-on time. The goal of objective 1 is to combine air sampling and detection into a one-step real-time POP AMS device that yields SARS-CoV-2 quantification results in less than 5 minutes, without lab equipment or reagents. Secondly, viral inoculum, or initial dose of virus, aspirated into the nasal cavity and lungs has been associated with disease onset and severity. The goal of objective 2 is to optimize and validate AMS to correlate readings from the air monitoring device with tissue-culture infectious dose (TCID50) and reverse transcription polymerase chain reaction (RT-PCR) quantities. These parameters can then later be applied to Human studies to determine the Human infectious dose of SARS-CoV-2 by aerosol transmission. Thirdly, field-based testing in hospitals will provide a means to beta test AMS performance in high-risk environments. The goal of objective 3 is to calibrate AMS measurements with RT-PCR cycle-threshold (Ct) values and cell-culture TCID50 viability results and then benchmark with results from high-risk environments taken from around the world to correlate SARS-CoV-2 aerosol concentrations with global infection rate, as a potential for establishing threshold levels.",2021,2024,N/A,2723214,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2021 +C15219,273201600002I-0-759602100016-1,TASK ORDER 16: USE OF INHALED HYALURONAN IN PATIENTS WITH SEVERE COVID-19,"COVID-19 is a potentially life-threatening infection by the coronavirus SARS-CoV2, which infects respiratory cells and induces epithelial injury, causing susceptible patients to develop adult respiratory distress syndrome (ARDS). ARDS leads to significant inflammation and accumulation of extracellular matrix (ECM), including hyaluronan (HA), a glycosaminoglycan sugar and abundant component of the lung ECM. HA is a powerful modulator of lung injury, inflammation and repair and is found in the airway lumen overlaying ciliated epithelial cells. Airway HA expression is induced by epithelial injury, including viral infection and recent reports highlight increased HA concentration in COVID-19 affected lungs as well. In cell culture and animal experiments we had found that therapeutic HA inhalation protects against SARS-CoV-2 infection. this study we explored the therapeutic role of HA COVID19-induced lung disease in patients with established moderate disease (admitted to hospital, in need for oxygen therapy). Specifically, we questioned whether inhaled HA may promote recovery from COVID19, since HA has antiviral, anti-inflammatory and pro-lung repair properties and ameliorates lung injury after a number of infectious and toxic exposures. We contracted with the Rome facility and initiated a study of inhaled HA (at least 10 days) or placebo. The outcomes were need for oxygen, and length of hospital stay.",2021,2022,N/A,225176,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Phase 2 clinical trial,2021 +C15220,3R01DA049666-03S1,Effects of Mu-opiate receptor engagement on the persistence of HIV-associated activation and viral reservoirs in individuals receiving medication assisted treatment for opioid use disorder,"SUMMARY The administration of effective anti- SARS-CoV-2 vaccines capable of eliciting a protective immune response in a large proportion of the population is a major public heath priority in combating Coronavirus disease 2019 (COVID-19). Our studies indicates that the functionality of soluble antibodies (i.e.: humoral immunity) is affected by chronic inflammation, such as chronic HIV infection and/or opioid use. Our short-term objective is to evaluate the quality and persistence of anti-SARS-CoV-2 antibody response in people living with HIV (PLWH) a) receiving a SARS-CoV-2 vaccination, b) on treatment with suppressive antiretroviral therapy (ART) and c) on treatment with mu opioid receptor (MOR) agonists methadone or buprenorphine for opioid use disorder (OUD). Based on the literature and our pilot studies, our primary hypothesis is that in ART-treated PLWH receiving MOR agonists-based treatment and SARS-CoV-2 vaccination will result in shorter retention of neutralizing titers and with different qualitative antibody responses [including lower antibody-dependent cell cytotoxicity (ADCC)/antibody-dependent cell phagocytosis (ADCP)] when compared to vaccine responses in ART suppressed PLWH who do not use opioids. To address this hypothesis, we will study a cohort of 90 PLWH receiving suppressive ART (VL < 50 c/ml) at approximately 4, 8 and 12 months from SARS-CoV-2 vaccination, in the following groups: (1) OUD on methadone, (2) OUD on buprenorphine/naloxone (Suboxone), and (3) ART- only non-OUD control. We will test our hypothesis by completion of the following aims: Specific Aim 1. To quantify functional anti-SARS-CoV-2 antibody responses by measuring: (a) SARS-CoV-2 antibody response by total binding antibody to Spike protein, and titers of neutralizing antibody against of Vero cells infected with wildtype SarsCoV2 (WA1/2020-Wuhan) or variants of concern (B.1.1.7-UK, or B.1.351-South Africa); (b) Anti-SARS-CoV-2 antibody activity in recruiting innate immune functions by complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). Specific Aim 2. To evaluate the relationships between SARS-CoV-2 antibody responses, immune activation and HIV latency by measuring: (a) Microbial translocation and mucosal integrity by assessing plasma markers of bacterial translocation (e.g.: sCD14, sCD163, LPS, EndoCAB), and mucosal structural integrity (e.g.: Intestinal fatty acid-binding protein (I-FABP) and Zonulin-1); (b) Levels of cell-associated HIV DNA (intact and total), HIV RNA (different transcript), and HIV transcriptional activity (ratio of HIVDNA/HIV RNA. The successful completion of this study will provide novel insights on the ability of ART-suppressed PLWH receiving treatment with MOR agonists to fully benefit from SARS-CoV-2 vaccinations.",2021,2024,N/A,156933,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Disease models | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2019 +C15221,1R21AI159928-01,In vivo tracking of inhaled ACE2 targeting theranostic nanodrugs delivery to the lungs using magnetic particle imaging,"ABSTRACT The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic with significant morbidity and mortality. Despite widespread efforts, it's far from certain that an effective vaccine will be available soon. Therefore, developing new therapeutics for this devastating disease is critically important. However, to date, no specific treatments are recommended to prevent or treat COVID-19. Previous studies have demonstrated that SARS-CoV-2 infects host cells through its viral spike glycoprotein interacting with cell-surface angiotensin-converting enzyme 2 (ACE2), which is a membrane-bound monocarboxypeptidase found in pulmonary alveolar epithelial type II (AECII) cells in the lung. An important function of ACE2 is to degrade angiotensin II, which limits several detrimental effects that result from angiotensin II binding to Angiotensin II type 1 (AT1) receptors, including vasoconstriction, enhanced inflammation, and thrombosis. The entry of SARS-CoV-2 into cells markedly down- regulates ACE2. Loss of ACE2 at the external site of the cell membrane results in increased pulmonary inflammation and coagulation. Nanoparticles are increasingly being proposed as lung drug delivery vehicles. Nanoparticles can also serve as imaging probes for theranostic strategies. Our long-term goal is to develop an effective and efficient protocol for manufacturing a wide range of therapeutic drugs to treat pulmonary infectious diseases using emerging siRNA and molecular imaging technologies. The overall objective of this project is to design a novel approach for introducing ACE2 targeting nanotherapeutics into pulmonary AECII cells to prevent interactions between SARS-CoV-2 and ACE2. These nanotherapeutics will also carry siRNA targeting the AT1 receptor to block the progression of inflammatory and thrombotic processes that local angiotensin II hyperactivity triggers following SARS-CoV-2 infection. In addition, the nanotherapeutics will have a superparamagnetic nanoparticle core, which can provide a way to non-invasively assess drug delivery using magnetic particle imaging (MPI). MPI provides high sensitivity detection and depth-independent quantitation for longitudinal studies. The output of this work will include a novel image-guided method for delivering nanodrugs to the lungs. This is significant because these nanodrugs will be capable of targeting ACE2-expressing cells, and preventing SARS-CoV-2 from entering the cells. These nanodrugs will also silence the expression of the AT1 receptor to block the progression of inflammatory and thrombotic processes that are normally induced by decreases in ACE2. This project will also demonstrate the utility of MPI for lung applications, such as evaluating the efficiency and uniformity of aerosol delivery, and tracking the aerosolized nanodrugs in vivo.",2021,2023,N/A,430375,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15222,1R21AI157903-01,RNA-dependent RNA Polymerase Assays for Biochemical Characterization and Antiviral Drug Discovery,"SARS-CoV-2 is a positive-sense, single-stranded RNA [(+)ssRNA] virus that relies on its RNA-dependent RNA polymerase (RdRp) for survival. Within the months of April and May, five groups have independently reported the production of recombinant SAR-CoV-2 RdRp and a preliminary activity assessment of this essential enzyme. Included in these studies was direct evidence that the triphosphate version of the nucleoside analogue remdesivir, which has received Emergency Use Authorization from the Food and Drug Administration to treat SARS-CoV-2, is incorporated in place of ATP into the growing RNA oligonucleotide, ultimately leading to chain termination. Other nucleobase and nucleoside analogues including EIDD-1931 and favipiravir, the latter of which has been approved in Japan to treat the (-)ssRNA influenza virus, have demonstrated promise as therapeutic agents against SARS-CoV-2 by likely interfering with RNA metabolism via inhibition or processing as alternative substrates for RdRp. This and other data suggest that RdRp is an excellent target for the discovery and development of novel SARS-CoV-2 therapeutics. However, one of the major bottlenecks in exploiting RdRp as a drug target is the relatively low throughput activity-based assays that are costly, prone to interference, and/or lack flexibility in the experimental design. The primary objective of this proposal is to develop a broadly applicable RdRp activity-based assay that will be used for antiviral drug discovery efforts. Our specific aim is to establish a novel, real-time assay using a five-enzyme coupled system with a colorimetric readout. The new assay will be directly compared to the traditional polyacrylamide gel electrophoresis and a liquid scintillation proximity end- point assay, and further validated with high resolution mass spectrometry. It is expected that, by accomplishing this aim, the assay will enable a thorough biochemical characterization of SARS-CoV-2 RdRp and, for the first time, enable the testing of synthetic compound and natural product libraries to identify inhibitors, alternative substrates, modulators, or effectors of SARS-CoV-2 RdRp activity in a high throughput screening format. Notably, the strategy implemented herein is expected to complement on-going structural-based anti-SARS-CoV-2 discovery efforts. Finally, the activity-based assay can be readily adapted for RdRp from other (+)ssRNA and (- )ssRNA viruses in an effort to identify therapeutics against a broad spectrum of pandemic-causing viruses.",2021,2023,N/A,417474,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2021 +C15223,1R01DK130478-01,Mechanism of the short- and long-term effects of COVID-19-induced Alarmins on hematopoietic stem and progenitor cells.,"ABSTRACT The long-term goal of this proposal is to understand the long-term sequalae of acute COVID-19 infection on hematopoietic and immune damages, and to identify the key pathways and mechanism by which COVID-19- associated cytokine dysregulation alters HSC function and differentiation. SARS-CoV-2 infection causes local and systemic damages due to dysregulated immune response and cytokine production. Its long-term negative effects on body tissue and organ remain largely unknown. Our published work showed that SARS-CoV-2 infection dramatically increased neutrophil production and neutrophil-associated S100A8/A9 (Alarmin) release. Persistent high level of S100A8/A9 is a negative prognostic biomarker for the disease severity and mortality. Although the function of S100A8/A9 on mature blood cells have been studied, its functional effect on hematopoietic stem cells (HSCs) are unknown. Our preliminary data show that S100A8/A9 causes loss of quiescence and differentiation of HSC toward myeloid progenitors at the expense of HSCs. Toll-like receptor 4 (TLR4), the endogenous receptor of S100A8/A9, is highly expressed in HSCs, and S100A8/A9 activates its canonical downstream MAPK (mitogen-activated protein kinase) pathway. Very interestingly, S100A8/A9 causes downregulation of epigenetic regulator Setd2, leading to the c-Myc upregulation in HSCs. c-Myc is a key downstream target of both MAPK and Setd2 pathways. MAPK, Setd2 and c-Myc are important regulators of HSC proliferation and myeloid differentiation. We hypothesize that SARS-CoV-2-induced S100A8/A9 activates TLR4 signaling which converts to c-Myc in HSCs, resulting in loss of quiescence and self-renewal, myeloid differentiation skewing, and long-term impairment of hematopoiesis. Since HSC is responsible for the life-long production of blood cells, including all types of immune cells, any functional damages of HSCs would later on have profoundly negative effects on the immune response. Therefore, understanding the cellular and molecular mechanism by which S100A8/A9 regulates HSCs and hematopoiesis would contribute a new evidence base to accelerate advances in diagnostics, therapeutics, clinical management of COVID-19 patients in acute infection and recovery phases. 1",2021,2024,N/A,401750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15224,1R21AI159655-01A1,Identification of olfactory mucosa protein fingerprints in COVID-19,"PROJECT SUMMARY A sudden onset of olfactory impairment is reported as one of the early clinical manifestations of COVID-19, particularly among mild and asymptomatic patients. Though reports indicate that olfactory loss resolves within two weeks, it is unknown what proportion of the patients develops persistent postinfectious olfactory dysfunction due to lacking longitudinal studies. Olfactory neuroepithelium, located in the olfactory cleft region of the nasal cavity, is venerable to SARS-CoV-2 infection. A known receptor to SARS-CoV-2, angiotensin- converting enzyme 2 (ACE2) is expressed in the non-neuronal cell types but not olfactory sensory neurons in the human olfactory epithelium. We hypothesize that SARS-CoV-2 infection in the olfactory epithelium produces an inflammatory microenvironment which in turn impacts on the function of olfactory sensory neurons. Systematic proteomics analysis of the olfactory mucosa microenvironment will facilitate the identification of COVID-19 induced inflammation and provide a better understanding of mechanisms in olfactory loss and recovery. To determine olfactory mucosal proteomics, we will sample the olfactory cleft region with nasal swab under the guidance of endoscopy and perform TMT-based quantitative mass spectrometry analysis to compare COVID-19 positive anosmic/hyposmic with non-COVID-19 normosmic subjects. We aim to 1. identify distinct protein fingerprints in Covid-19 olfactory mucosa; 2 perform longitudinal analysis of olfactory mucosa proteomes to predict olfactory recovery. Data established through this study will also help identify COVID-19 biomarkers, guide therapeutic strategies, and provide insight into the general mechanism of SARS-CoV-2 triggered inflammation and its impact on neuronal functions.",2021,2023,N/A,235500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15225,3U24MD016258-02S1,RADx-UP SAY YES COVID Test Study (S4),"This supplement will follow the approved Abstract under RADx-UP 3U24-MD016258-01S1. As requested by the NIH, we will deploy the SAY YES! COVID Test pilot in two additional communities likely to experience surges in SARS-CoV-2 infections. These additional communities will not be subject to the sub-study.",2021,2024,N/A,5500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,,,2020 +C15226,3U01HL146245-03S1,MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS),"ABSTRACT MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV-infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative for their health that they be vaccinated with the new COVID-19 vaccines. To date, however, there are only anecdotal data on COVID-19 vaccine acceptance and efficacy in people with HIV (PWH). The MWCCS is ideal for analyzing (a) the acceptancy and effects of COVID-19 vaccine(s) in male and female PWH and matched HIV-uninfected controls (HUC), (b) the impact of age and co-morbidities on vaccine immune response and protection against COVID-19, and (c) the social, economic, and behavioral changes after COVID-19 immunization as compared to the individuals who opted to not take the vaccine. To address this issue, we will have 2 groups of MWCCS participants in this study: Group A: Male and female PWH and HUC who choose to receive a COVID-19 vaccine, Group B: Male and female PWH and HUC who choose NOT to receive a COVID-19 vaccine. The aims of our proposed longitudinal observational study for this OAR Innovation application are: Aim 1: To conduct an MWCCS-wide, mixed-methods investigation of the prevalence, correlates, and nuances of COVID-19 vaccine hesitancy among MWCCS participants. Results will help better understand the concerns of PWH and HUC populations regarding COVID-19 vaccines based on age, sex, race/ethnicity, and underlying comormidity burden. Aim 2: To determine the incidence of natural SARS-CoV-2 infections post-COVID-19 immunization in PWH as compared to HUC of the same age, sex, and ethnicity/race and also compare with the incidence of infections in non-vaccinated individuals. Because of budgetary limitations in the OAR Innovation Fund supplement, we will restrict Aim 2 to obtaining one specimen at baseline, just prior vaccination in Group A, and within comparable time periods for Group B. Subsequent samples collected during the core MWCCS visits will be used in the serological analyzes. These samples will allow us to determine the serological COVID-19 status pre-immunization, and post-immunization seroconversions for S and N proteins. The titration of anti-S responses post immunization will indicate vaccine immune response, while anti-N antibody titers will indicate natural SARS-CoV-2 infection This information will allow the identification of asymptomatic and symptomatic individuals infected with SARS- CoV-2 post-vaccination and in non-vaccinated group. The if these infections in the MWCCS will allow a targeted use of core samples in depth investigation of the immune mechanisms of vaccine-mediated protection, the immunologic responses and virologic characteristics of breakthrough SARS-CoV-2 infections, and the impact of the vaccination on underlying HIV infection. Importantly, timely funding from this OAR Innovation opportunity is critical to our addressing these aims prior to the broad rollout of the COVID- 19 vaccines to our PWH participants. We are in a race to obtain this critical information and specimens prior to the wide availability of current FDA EUA vaccines to our MWCCS participants. The MWCCS clinical research sites across the United States and the data center are ready to launch this new study as soon as funding is available and we receive sIRB approval.",2021,2026,N/A,31348,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Characterisation of vaccine-induced immunity | Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15227,1R56AG073226-01,"Shorter T-cell telomeres, lymphopenia, and high mortality of older people with COVID-19","SUMMARY The familiar assertion that older persons are more likely to die from COVID-19 because of their declining immunity is factual but also reductive. This project seeks to generate more specific insight into the high COVID- 19 mortality among older adults by focusing on the role of T-cell telomere length (TL) in the lymphopenia that often develops in patients infected with SARS-CoV-2. The central hypothesis posits that COVID-19 patients with short telomeres are more likely to develop severe T-cell lymphopenia, less likely to normalize their T- cell count during the course of the disease, and therefore less likely to clear the virus and recover. It is directly relevant to aging because TL shortens with age, and older age poses a heightened risk of severe disease after infection with SARS-CoV-2. The work will also explore the potential role of T-cell TL in suppressing the innate immune response, a major contributor to the ""cytokine storm"" that is largely mediated by pro-inflammatory monocytes. The project will study 417 adults hospitalized with COVID-19, half of whom with a severe form of the disease indicated by admission to the ICU. Blood samples will be collected on admission (time point T1), at day 3 (time point T2) and at day 7 (time point T3). All-cause mortality will be determined up to 30 days after T1. As very short telomeres, not mean telomere length, undermine cell viability, T-cell TL parameters will be quantified by the novel Telomeres Shortest Length Assay (TeSLA), a method that detects and measures short telomeres, including those below the range detectable by standard methods. Aim 1 will examine the relation of T-cell TL parameters at T1 with mortality. It will test the hypothesis that short T-cell TL at T1 predicts mortality, and that T-cell lymphopenia at T2 is a mediator of this relationship. Aim 2 will probe deeper into the relation between T- cell TL parameters at T1 and mortality, testing the hypothesis that older age drives the pathway examined in Aim 1. The findings of these two aims will generate new knowledge about the relation between aging, T-cell TL parameters and T-cell lymphopenia, and test models that postulate causal effects of these factors on all-cause mortality in COVID-19. Aim 3, an exploratory aim, will examine the relation of T-cell TL parameters with selected cytokine levels and monocyte subsets in blood samples donated by 50 participants in Aims 1 and 2. This aim represents the first step of examining the role of T- cell TL in the innate immune response to infection by SARS- CoV-2. Findings of the study have the potential to transform understanding of the causes of COVID-19 lymphopenia, elucidate the mechanism underlying the relationship between older age and COVID-19 mortality, and motivate development of new treatments. They may also be relevant to understanding adaptive responses of older adults to vaccination against SARS-CoV-2. Finally, insight generated by this project will be important for not only the present pandemic but also outbreaks and pandemics by other β-coronaviruses that will almost certainly happen in the future.",2021,2022,N/A,321850,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +C15228,1R01AA029921-01,Understanding longitudinal relationships between COVID-19 pandemic outcomes and alcohol use and problems from 2019 to 2020 and 2021 for the U.S. population and vulnerable groups.,"ABSTRACT The COVID-19 (C19) pandemic has upended American lives with far-reaching consequences for health and well-being, and has disproportionately impacted racial/ethnic minorities and other vulnerable communities. Studies from the early pandemic period have observed increases in alcohol use and heavy drinking, and these behaviors and their consequences on physical and mental health are expected to persist well after the pandemic subsides. Thus far, however, there is a dearth of nationally-representative, longitudinal data on the pandemic's effects on alcohol and drug use and mental health that build on baseline pre-pandemic data. The Alcohol Research Group and its P50 Alcohol Research Center have conducted a series of National Alcohol Surveys (NAS) for forty years. We conducted the 14th edition of the NAS (N14) beginning in 2019 and completed it on April 20, 2020, and in early 2021 we conducted a NAS COVID supplement survey (N14C) as a follow-up of N14 (baseline) respondents. With this rapid-response R01 application we are proposing to conduct a 3rd wave of data collection of N14 and N14C respondents (termed N14C2) to build a nationally-representative cohort with 3 survey time-points. With pre-C19 data from the first wave of data collection, N14, and two follow-up surveys covering the first (N14C) and second (N14C2) years following initial efforts to control C19 spread in the US, we will be able to rigorously assess the financial, social, and health impacts of the C19 pandemic on alcohol and other drug (AOD) use and problems. We will investigate the potential impact of increased alcohol use on the course of consequences of the pandemic, such as job loss, social contact and mental health outcomes. We also propose to examine alcohol use and C19-related precautionary behaviors such social distancing, and vaccination uptake. We will contextualize the analysis by including geocoded data linked to our survey data to allow us to examine these associations in relation to relevant C19-related state policies, available alcohol purchasing options, and other area conditions that may affect AOD use and problems. Finally, we propose to apply mixed methods to understand in depth alcohol use experiences during the pandemic and perceived need, barriers, facilitators and plans for seeking support among heavy drinkers in subgroups disproportionately affected by the pandemic, namely Blacks, Latinos, and sexual minorities. To accomplish this we plan to recruit a purposive subsample for semi-structured qualitative interviews following the N14C2 survey. Taken together, this project will identify and characterize those at an increased risk of developing AOD problems, poor mental health, and prolonged C19 impacts, and determine features of environments including regulations that increase or mitigate these risks, aiming to inform modifiable interventions and policies.",2021,2024,N/A,360450,Human Populations,Black | Other | Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Sexual and gender minorities | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Secondary impacts of disease, response & control measures","Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Supportive care, processes of care and management | Restriction measures to prevent secondary transmission in communities | Indirect health impacts",2021 +C15229,1R01HL160046-01,Mechanisms linking the plasminogen/fibrinogen axis to the pathogenesis of COVID-19,"SUMMARY Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; CoV2) is the first highly pathogenic and highly transmissible human coronavirus that is the causative agent for the worldwide COVID-19 pandemic. As of November 2020, 50 million cases of CoV2 infection worldwide and 1.25 million deaths have been reported. The U.S. accounts for the majority of cases, 9.7 million (20%) and deaths 235,000 (19%), and COVID-19 is expected to add an $8 trillion burden to the U.S. health care system. A particularly challenging aspect of clinical management is the variable patient response to CoV2 infection. Some infected individuals report few symptoms whereas others display severe disease characterized by hypoxia, acute respiratory distress syndrome, and multi-organ involvement that can lead to death. A pro-inflammatory 'cytokine storm' in COVID- 19 patients promotes derangements in vascular function and blood composition. Elevated fibrinogen and D- dimer (the breakdown product of fibrin clots) track with significant elevations inflammatory markers (e.g., IL-6, C-reactive protein), which significantly and positively correlate with poor patient outcomes. Autopsy studies of COVID-19 patients have revealed intravascular and extravascular fibrin deposits in lung tissue and other organ systems. A current critical knowledge gap is the molecular basis of how persistent fibrin deposits develop and whether they are functionally linked to the pathophysiology of severe COVID-19 disease. Our central hypothesis that an insufficiency in the plasminogen activation (PA) system is a trigger point for transition of COVID-19 from mild to severe disease due accumulating, proinflammatory, and tissue-damaging fibrin deposits within the lung and other organ systems. To test this hypothesis, our research team developed a mouse-adapted CoV2 virus that replicates key immunological and hematological aspects of COVID-19 in humans. This unique tool will be used in conjunction with mice carrying single or combined deficiencies or functional mutations in fibrinogen or PA system components to define the natural course of hemostatic changes following infection and elucidate functional contributions of coagulation and fibrinolytic factors to the host response. Specifically, we will determine (i) the differences in local and systemic activity of host factors that control fibrin(ogen) deposition, stabilization, and dissolution following mild vs. severe CoV2 infection; (ii) how PA deficiency promotes severe disease following CoV2 infection characterized by exacerbation of local and systemic inflammatory, organ damage, and host mortality; and (iii) the mechanisms linking fibrin(ogen) to exacerbation of host inflammatory responses and induction of severe disease following CoV2 infection. The proposed studies will provide novel insights into the contribution of the plasminogen/fibrinogen axis to the CoV2 pathobiology, illuminate key mechanisms coupling deficiencies in PA system components to CoV2- mediated thrombophilia, tissue damage, and loss of organ function, and provide essential proof-of-principle data to facilitate translation of findings into new treatments for COVID-19.",2021,2025,N/A,580295,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease models | Disease pathogenesis",2021 +C15230,3U42OD012210-22S1,MMRRC COVID-19 variant testing in humanized mouse models,"ABSTRACT & SCOPE OF WORK The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC-UC Davis) is pleased to submit this administrative supplement for up to 1 year of support in response to ORIP's participation in PA-20-272, ""Administrative Supplements to Existing NIH Grants and Cooperative Agreements"" specifically related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). This application addresses a number of the stated objectives of the call to support COVID-19 related research, including to develop and characterize animal models for post-acute sequelae of COVID-19 (PASC) and to study the susceptibility of existing COVID-19 animal models to emerging viral genomic variants. Specifically, this application will generate polygenic humanized mouse models for virus challenge, validation, and post- acute sequellae of COVID-19 (PASC) in both young and aging mice using well-established testing and screening platforms in an ABSL3 environment. This project will build upon our successful efforts to generate monogenic humanized knockin/murine knockout mouse lines for several genes (ACE2, TMPRSS2, and FURIN) involved in SARS-CoV-2 binding, entry, and activation. With this prior experience in hand, we now propose to determine infectivity and transmission in new polygenic humanized mice to assess the extent to which they can be used as suitable models of PASC in humans. Specifically in this project we will 1) use in vitro fertilization (IVF) expansion and intercrossing of our extant monogenic models to rapidly generate polygenic humanized mouse models of hACE2/hTMPRSS2 and hACE2/hTMPRSS2/hFURIN, 2) validate the pathophysiological effects and assess PASC after challenge with currently dominant circulating (B.1.1.7; strain: USA/CA_CDC_5574/2020) in young and aging male and female cohorts of polygenic humanized mice under ABSL3 conditions, and 3) establish breeding colonies and cryopreserved germplasm of humanized mouse models for archiving and distribution to the biomedical research community. Validation studies will involve systematic characterization of viral load and clearance, body weight kinetics, and lung inflammation after SARS-CoV-2 challenge of male and female cohorts of mice; positive results will be communicated to the ACTIV-Preclinical Working Group and others at NIH. In addition, observational and pathological screening of surviving aging mice will be conducted to screen for evidence of PASC; promising findings will be communicated with members of the PASC Initiative and Investigator Consortium (OTA-21-015A and B) and other NIH staff to ensure rapid translation of findings for human studies and functional studies in animal models. Further, we will ensure that our mouse models and testing platform will be made readily available for use by other researchers to swiftly assess the in vivo consequences of not only newly appearing SARS-CoV-2 variants that escape current therapeutic and vaccine strategies but also of future viruses with similarly high- impact pandemic potential. This study is essential to overcome genetic discrepancies between mouse and human and to fill crucial gaps in existing small animal models of COVID-19 that hinder translation of research findings to improvements in human health, including understanding the development, treatment, and prevention of PASC, the effectiveness of antiviral therapies, and the reliability of disease-prevention vaccine strategies.",2021,2025,University of California-Davis,498821,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Post acute and long term health consequences,2021 +C15231,3U01HL146194-03S1,Innovation Fund Application to the Multicenter AIDS Cohort Study MACS/WIHS Combined Cohort Study (MWCCS) COVID-19 Vaccine Acceptance and Hesitancy (CVHB) Study in People with HIV,"MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV-infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative for their health that they be vaccinated with the new COVID-19 vaccines. To date, however, there are only anecdotal data on COVID-19 vaccine acceptance and efficacy in people with HIV (PWH). The MWCCS is ideal for analyzing (a) the acceptancy and effects of COVID-19 vaccine(s) in male and female PWH and matched HIV-uninfected controls (HUC), (b) the impact of age and co-morbidities on vaccine immune response and protection against COVID-19, and (c) the social, economic, and behavioral changes after COVID-19 immunization as compared to the individuals who opted to not take the vaccine.",2021,2026,N/A,26713,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Immunity | Characterisation of vaccine-induced immunity | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15232,3R01AG059502-04S1,Preclinical studies to establish the combination of apoA-I mimetic peptides and statins as novel therapy for COVID-19,"PROJECT SUMMARY/ABSTRACT The SARS-CoV-2 pandemic emphasizes the urgent need to determine pathways that can be targeted by novel antivirals. This proposal describes the use of the combination of apoA-I mimetics with statins as novel therapy for COVID-19. SARS-CoV-2 utilizes mitochondria to replicate in lung epithelial cells. Mitochondrial reactive oxygen species (mito-ROS) induce alterations of lipids, membranes and redox sensitive proteins and ultimately viral replication. Thus, we hypothesized that the antioxidant ApoA-I mimetic peptide 4F, that targets lipids, mito-ROS and redox pathways, has antiviral activity against SARS-CoV-2. We confirmed that 4F not only has antiviral activity against SARS-CoV-2 but also has anti-inflammatory effects in epithelial cells that may alleviate lung injury in COVID-19. Importantly, prior studies have shown that 4F and statins may have major additive in vivo effects on altered lipids, oxidative stress and inflammation that are instigators of cardiovascular disease. Human studies suggest that statin use was associated with a lower risk of developing severe COVID-19. Both statins and 4F attenuate activation of the Toll like Receptor (TLR)-CD147-NF-κB pathways, which are key inflammatory pathways in coronavirus infections. We hypothesize that the combination of 4F and statins has antiviral activity against SARS-CoV-2 in lung epithelial cells and anti-inflammatory activity in lung epithelial cells, macrophages and vascular endothelial cells by attenuating the redox sensitive TLR-CD147-NF-κB proviral and proinflammatory pathway. Thus, in Aim 1 of this proposal and using an air-liquid interface (ALI) culture of primary airway epithelial cells, and cell lines in combination with viral and immune assays, we will determine the mechanisms how the combination of 4F with atorvastatin attenuates aberrant activation of the TLR-CD147-NF-κB pathway as a novel mechanism that drives viral replication and associated inflammatory responses in SARS-CoV-2 infected lung cells. Given that vascular dysfunction is a possible mechanism of chronic post-infectious sequalae of COVID-19, in Aim 2 of this proposal and using an established ex vivo model of atherogenesis and vascular dysfunction and peripheral blood mononuclear cells (PBMCs) from COVID-19 patients in combination with immune assays, we will determine whether 4F and atorvastatin attenuate aberrant activation of the TLR-CD147-NF-κB pathway in macrophages from COVID-19 patients that interact ex vivo with endothelial cells to drive proinflammatory proatherogenic responses. Our independent aims will complement each other and will advance the use of the combination of apoA-I mimetic peptides and statins as novel therapy for COVID-19. This work is innovative, interdisciplinary, public health-oriented, and directly addresses the goals of funding opportunity.",2021,2023,N/A,335400,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies | Prophylactic use of treatments",2018 +C15233,1R56AI159536-01,The cellular mechanisms of immunological memory development in COVID-19 patients,"The recent unexpected emergence of the COVID-19 pandemic has spurred significant interest in an improved understanding of immunological memory to SARS-CoV-2, which consists of humoral (neutralizing antibodies) and cellular (T and B cells) memory. The generation of immunological memory to the SARS-CoV-2 virus critically depends on T cell responses. During a viral infection, CD4 helper T cells differentiate largely into either Th1 cells that orchestrate a type I antiviral immune response or follicular helper (Tfh) cells that enhance antibody production. CD8 T cells clonally expand and acquire effector function to directly kill virus-infected cells. Despite the heterogeneity and clonal diversity of virus-specific T cells, the majority of effector T cells die after viral clearance and only a small portion of them develop into memory T cells that provide long-lasting protection for the host. Similarly, B cells develop into memory B cells and long-lived plasma cells that produce neutralizing antibodies. Snapshot observations with multi-parameter flow cytometry-based assays along the course of infection has yielded abundant knowledge of T cell phenotypic and functional diversity. However, approaches as such fail to address the developmental trajectory of virus-specific T cells. This becomes more obvious in human studies given that lineage tracing by genetic alterations or adoptive transfer experiments, done easily in mice, are inherently difficult or impossible in humans. In this proposal, we will first combine newly developed single- cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) techniques on the same cells and use TCR sequences as natural barcodes to directly ""lineage trace"" each patient's SARS-CoV-2-specific CD4 and CD8 T cell effector response and memory formation at the single-cell level throughout the course of natural infection. Furthermore, we will perform gene regulatory network (GRN) analysis to delineate which transcription factors collaboratively regulate virus-specific CD4 and CD8 T cell differentiation trajectories. Next, we will measure T cell clonal diversity and the quality of T cell memory from COVID-19 patients as well as healthy human controls. The latter will be used to gauge the possible presence of pre-existing immunity (PEI) in the form of memory T cells derived from cross-reactivity to common coronaviruses. These measurements will use high- throughput RNA-seq of TCR amplicons and scRNA-seq of memory T cells from recall cultures as inputs for computational TCR motif analysis. Lastly, successful vaccine development relies on an advanced understanding of the types of Tfh cells that are generated during natural infection and how they interact with B cells as well as T regulatory cells for anti-SARS-CoV-2 antibody production in humans. To this end, we propose to monitor circulating Tfh cells, including three major populations (Th1-, Th2- and Th17-like subsets), and T follicular regulatory (Tfr) cells in both SARS-Cov-2-infected and healthy human control subjects. In addition, we will perform T cell-B cell coculture assays to dissect the functional contributions of each subset of Tfh cells and how they interact with Tfr cells in regulating anti-SARS-CoV-2 neutralizing antibody responses.",2021,2022,N/A,749896,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C15234,3R37AI080289-12S1,Defining humoral correlates of immunity against COVID-19,"Since 2002, several coronaviruses have emerged able to cause severe respiratory disease, however no vaccine is available to prevent these rapidly spreading pathogens. Vaccine design has specifically lagged due to our lack of understanding of the correlates of immunity against these pathogens. Both cellular and humoral immune responses have been implicated in resolution of disease, but to date only the passive transfer of antibodies has been shown to confer complete protection in mice. Interestingly, the transfer of both ""neutralizing"" and nonneutralizing antibodies have shown protective efficacy, highlighting the role of multiple humoral mechanisms in limiting viral infection/spread. The precise mechanism of action of these antibodies that have the most profound impact on limiting disease is currently unclear, but if elucidated could provide critical insights for the development of effective vaccines against COVID-19 and other coronaviruses. Thus, here we aim to take a systematic approach to dissect and define both the polyclonal and monoclonal mechanisms by which antibodies confer protection against COVID-19. Specifically, samples from DNA- and adenovirus 26 (Ad26)- COVID-19 Spike protein (S) immunized animals, that will be challenged with COVID-19, will be comprehensively profiled using Systems Serology, to define the functional humoral immune responses linked to protection from infection/disease in mice, ferrets, and macaques. Machine learning modeling will be employed to discern key immune response features that translate usefully across these diverse animal contexts. These studies will not only define correlates of immunity across vaccines and species, but also provide mechanistic insights into the precise mechanisms by which antibodies may confer protection in the context of future vaccines.",2021,2022,N/A,749896,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C15235,2U19AI125357-06,Surfactant Protein-A and Type 2 Asthma in SARS-CoV-2 Infection,"During the first cycle of our AADCRC program, our project focused primarily on Surfactant Protein A (SP-A), a known innate immune modulator that exhibits important anti-inflammatory effects in asthma. In this renewal, we show preliminary data that SP-A binds the interleukin (IL)-6 receptor and disrupts IL-6 signaling, events relevant to specific asthma phenotypes. While this work was progressing, the Severe Acute Respiratory Syndrome- related Coronavirus 2 (SARS-CoV-2)-driven coronavirus disease 2019 (COVID-19) pandemic emerged and has fundamentally changed our world. Elevated serum IL-6 is a hallmark of the ""cytokine storm"" associated with severe COVID-19 acute respiratory distress and IL-6 inhibitors show promise as treatments. Our data suggest that SP-A exhibits innate functions relevant to SARS-CoV-2 infection by inhibiting IL-6 signaling intermediates and also by binding to angiotensin converting enzyme-2 (ACE2), the receptor used by SARS-CoV-2 for entry into host cells. These findings suggest that SP-A may attenuate the inappropriate innate immune responses in COVID-19 and by this mechanism, could play a role in the treatment of SARS-CoV-2 infection. Several chronic lung-based comorbidities have been shown to increase the severity and mortality associated with COVID-19 - with the notable exception of asthma. Evidence from our group suggests that type-2 (T2) cytokines such as IL-4 and IL-13, which are critical molecular underpinnings of atopic asthma, reduce ACE2 expression in airway epithelial cells from T2 asthma. These findings suggest that atopic asthma-associated T2 cytokines protect against COVID-19 by modulating infection. In this AADCRC renewal, we will build on these preliminary data and merge two complementary, unique lines of investigation to expand the focus of our proposal and investigate the interplay of SP-A and T2 cytokines at both the initiation and the effector stages of SARS- CoV-2 respiratory tract infection in asthma. We will test the novel hypothesis that SP-A effectively limits COVID- 19 by decreasing ACE2-mediated events through direct receptor binding and inhibition of IL-6 signaling pathways. In the setting of atopic asthma, type-2 cytokines may reduce the susceptibility to SARS-CoV- 2 infection by inhibiting ACE2 expression and function. In aim 1, we will determine the impact of SP-A in limiting SARS-CoV-2 infection of human nasal, bronchial and distal airway epithelial cells and whether these effects depend upon ACE2 binding and modulation of IL-6 signaling. In aim 2, we will assess ACE2 expression in nasal, bronchial and distal epithelial cells from normal atopic and non-atopic controls and T2 asthmatic participants, and determine how T2 cytokines and virus-induced interferons interact to regulate epithelial cell ACE2 expression and SARS-CoV-2 infection in these cells. We hypothesize that SP-A and T2 cytokines can synergize to dampen both the initiation and the effector phases of SARS-CoV-2 infection, thereby protecting from COVID-19. This proposal leverages expertise in asthma, SP-A immune responses, virology and epithelial biology within the project and synergizes well with Projects 1 and 2 to better understand viral insults in asthma.",2021,2026,N/A,371166,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2016 +C15236,1R21AI161678-01,Targeting Coronavirus through Nucleocapsid Phosphorylation,"Summary Coronaviruses express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV (responsible for SARS) by glycogen synthase kinase 3 (GSK- 3) is required for its function. GSK-3 inhibition attenuates infectivity of SARS-CoV and other coronaviruses and is therefore an intriguing therapeutic strategy for coronavirus infections. Lithium, a widely used medication, directly inhibits GSK-3 and impairs N phosphorylation, viral transcription, replication, and infectivity of diverse coronaviruses. However, GSK-3 phosphorylation of N protein from SARS-CoV-2 (the cause of COVID19) has not been reported. This proposal leverages our long-standing expertise with GSK-3 to block N function and SARS-CoV-2 replication. In a preliminary review of 70,000 subjects undergoing PCR testing for SARS- CoV-2, we found that patients on lithium had reduced risk of COVID19 (odds ration = 0.5 [0.36 - 0.80], p = 0.0002). We show that phosphorylation of N from SARS-CoV-2 is inhibited by lithium and that other GSK-3 inhibitors block N phosphorylation with IC50s in the low micromolar range. GSK3 loss of function supports that GSK-3 is required for SARS-CoV-2 N protein phosphorlyation. We identified clinically-tolerated drugs that unexpectedly inhibit GSK-3 and impair N phosphorylation at clinically-tolerated levels. Aim 1 of this proposal describes approaches to enhance inhibition of N phosphorylation by lithium and by selective GSK-3 inhibitors, with a focus on those shown to be safe in humans through clinical trials for other diseases. As GSK-3 phosphorylation of N protein requires pre-phosphorylation at a distinct site by another, unkown protein kinase, Aim 2 will identify and target the priming kinase as an alternative strategy to block SARS-CoV-2 transcription and replication. This aim will also test whether inhibitors of either GSK-3 or the priming kinase interfere with replication of other pathogenic coronaviruses. If successful, the project will identify clinically safe medications that can be repurposed to treat COVID19 as well as future coronavirus outbreaks.",2021,2023,N/A,446875,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15237,3P51OD011133-23S2,Baboon model of long term effects of SARS-CoV-2 infection,Abstract. Nonhuman primate (NHP) models of SARS-CoV-2 infection showed mostly mild disease. Infection of old-world origin baboons however showed moderate disease especially with significantly more lung pathology and evidence of viral dissemination to extrapulmonary tissues. Baboons are therefore an important model to study the pathogenesis of SARS-CoV-2 infection and identify therapeutic approaches to control COVID-19. We hypothesize that a study of long term effects of COVID-19 in the lung and other compartments is therefore best studied in a model like baboon. Here we propose experiments to address this issue.,2021,2026,N/A,499742,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15238,1R21EB031310-01,A Rapid and Sensitive Technology for Direct Sensing of Intact SARS-CoV-2 Virions Using Designer DNA Nanostructure Probes and a Smartphone Fluorimeter,"Abstract The rapid development of the COVID-19 pandemic reveals the shortcomings of current technologies for diagnosis. The limited availability, insufficient sensitivity and/or specificity of gene-based and antigen/antibody- based tests resulted in relatively high rates of false negative/positive test results, which further led to failure of patient quarantine and confusion among health authorities and the public. The fundamental limitations of current gene-based assays stem from their reliance upon amplification and detection of specific nucleic acid sequences within the viral genome. The current test requires labor-intensive, laboratory-based sample preparation protocols for virus lysis, extraction of genetic materials, purification of the isolated materials, thermal cycling for enzymatic amplification of viral nucleic acid sequences, and interpretation of complex results by professionals. We seek a new paradigm for rapid and direct pathogen detection, identification, and quantification in which the intact virions are directly recognized through their distinct surface epitope features, and the resultant fluorescent signal is immediately captured by a portable, smartphone-based fluorimeter. To achieve specific recognition of SARS- CoV-2 virions, we customized a designer DNA nanostructure (DDN)-based capture probe that harbors a macromolecular ""net"" whose vertices precisely match the intra- and inter-spatial pattern of SARS-CoV-2 trimeric spike glycoprotein clusters, and integrates a net-shaped array of SARS-CoV-2 spike specific-targeting aptamers that are designed for maximum affinity and specificity when binding with spikes in a polyvalent and pattern- matching fashion. When exposed to a test sample, such as saliva or nasopharyngeal swab material in solution, the DNA rhombus-shaped ""virus nets"" rapidly and selectively bind intact virions to trigger the release of fluorescence. We have successfully developed a smartphone-based instrument that can detect and quantify fluorescent signals in point-of-care (POC) settings. Thus, the fluorescent signal released from the virus net upon binding to SARS-CoV-2 can be readily detected by our smartphone-based fluorimeter in POC settings. We propose to combine DDN capture probes and a smartphone fluorimeter for the first time, to develop and demonstrate a rapid, room temperature, single-step, virus-specific, and ultrasensitive diagnostic assay for COVID-19 that can be performed immediately after sample collection at the point of care, and provide a result in < 5 minutes. Our aims include development of a COVID-19 assay in POC settings, and statistically robust characterization of its sensitivity, specificity, reproducibility and cost-effectiveness. Our study will conclude with a preliminary validation of the system using clinical specimens and direct comparison against a gold-standard laboratory PCR test.",2021,2023,N/A,422226,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15239,1R21AI161212-01,Defining therapeutic drug targets for SARS-CoV-2-specific and pan-coronavirus inhibition,"Project Summary COVID-19 disease, caused by severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is currently ravaging the world. Infection of humans causes symptoms spanning the spectrum from asymptomatic infection to severe respiratory distress and death. Despite the fact that vaccines and repurposed drugs are currently under study, it is uncertain whether they will be efficacious and so efforts to develop additional treatment and preventative options are crucial. This study will leverage results from multiple bulk CRISPR knockout screens already performed in the lab that identify host factors that SARS-CoV-2 and other human coronaviruses require for replication. These screens utilized cells from two tissue sources, lung and liver, four human coronaviruses including SARS-CoV-2, two temperatures that mimic the upper and lower airway, and five different CRISPR libraries including three druggable genome libraries, a library focused on human factors recently discovered to interact with proteins of SARS-CoV-2 and a full genome library. In the first aim, factors identified as hits in each of the screens will be cross compared and prioritized into three categories: 1) specific to SARS-CoV-2, 2) common to SARS-CoV-2 and at least one other coronavirus, or 3) specific to the lung for any of the viruses (Aim 1a). Hits from these categories will be subjected to refinement using a semi-arrayed CRISPR approach (Aim 1b) as well as drug and small molecule inhibition assays (Aim 1c) in the context of a panel of coronaviruses. In the second aim, gene disruption of the prioritized targets will be performed in primary human lung cells (Aim 2a) and the effect on the replication and cell killing by a panel of coronaviruses, including SARS-CoV-2 will be determined (Aim 2b). Drugs and compounds found as antiviral in Aim 1c will be tested in the primary human lung cells for their antiviral activity against the coronavirus panel. Validated factors, which could be SARS-CoV-2-specific, or possibly factors required generally for coronaviruses, would be targets for future in depth mechanistic studies and drug development.",2021,2023,N/A,483500,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +C15240,1R43EB030947-01A1,In Vivo Cluster AI Prediction (CLAIRE) of COVID-19 Disease Progression,"ABSTRACT The coronavirus COVID-19 pandemic, which early this year forced entire countries into lockdown, has reached a global death toll of 890,000+ by early September 2020. Based on the high number of COVID-19 cases that are asymptomatic but infectious, an estimated reproductive rate of infection of about 2 and a high mutation rate, it is expected that the virus will remain in the population as the influenza virus does. For hospitals serving areas whose economy relies on international travel, tourism, and cruise ship tourism, such as Miami-Dade county, new COVID-19 cases related to travel will require treatment during infection outbreaks which will strain health systems, especially during the infectious respiratory disease season in the winter. Patient risk factors during the current COVID-19 outbreak as well as during other viral outbreaks, such as seasonal influenza, are poorly characterized, consequently negatively affecting patient care. The saliva microbiome, which includes viruses and bacteria, is not currently used as in diagnostic tools. However, it may reveal risk factors associated with severe disease and/or a fatal outcome, and it allows for the detection and study of the viral RNA sequence for potential contact tracing and molecular epidemiology, all of which affect both vaccine and antiviral efficacy. In this proposed study, Lifetime Omics will develop CLAIRE, a proof-of-concept in vivo cluster AI platform for predicting disease progression of viral infectious respiratory diseases such as COVID-19 through the analysis of the saliva metagenome. The University of Miami Medical Group Infection Control (UMMGIC) division will collaborate in this effort by collecting saliva samples from COVID-19 patients with de-identified clinical information. The samples will undergo metagenomic sequencing and Lifetime Omics will repurpose algorithms used for prediction of in vivo HIV evolution to perform genetic/phylogenetic analysis on SARS-CoV-2 RNA sequences, estimating mutation rate and immune selection pressures and identifying both the in vivo quasispecies clusters and the geographic cluster to which the patient belongs. The CLAIRE models will be trained with public datasets and tested on the metagenomic sequences generated from saliva samples of UMMGIC patients with the goal of assisting physicians in predicting disease progression in COVID-19.",2021,2022,The University of Miami Medical Group Infection Control (UMMGIC),248723,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2021 +C15241,1R21AI164551-01,Rapid detection of infectious viral particles by cluster induced exhaustive reaction,"Summary The COVID-19 pandemic has posed enormous challenges to health, economy, environment and immigration in the US. Enhancement of diagnosis capacity together with restriction policies has been widely implemented to contain the virus spreading. However, there are still over 200,000 deaths and half million hospitalized in the US alone. The virus, Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), is highly contagious while early infection particularly in young adults often exhibits no symptoms when they are actively transmitting viruses in the community through speaking and breathing. These two transmission approaches normally emit much lower number of virus particles in aerosols than coughing and sneezing, and thus are difficult to detect. Despite many types of diagnostic tools available, current on-site diagnostic technologies do not have the sufficient sensitivity and speed to detect low number of virus particles in aerosols emitted by infected people. The gold standard method, polymerase chain reaction (PCR), and its variants are only ultrasensitive in the lab setting to detect low copy number of viruses. Emitted aerosols are attractive target for clinical diagnosis because sampling is not invasive, and the detection results directly determine whether a person is spreading viruses or not. To address the above challenge, we will develop a rapid diagnostic technology based on cluster induced exhaustive reaction (CIER) with the few virus sensitivity and disposable device with the cost of pennies, so that this kind of paper device can be used frequently anywhere to identify an infectious individual immediately before he/she further spreads SARS-CoV-2 to the community. CIER enables theoretically unlimited amplification of signal while maintaining high specificity, and thus is highly applicable to detect SARS-CoV-2 particles where only the compact cluster of antigens can trigger the CIER sensor. Two specific aims are proposed: (1) Construct CIER sensor by assembling antibodies, spacer and HRP moieties, and optimize CIER's design for detecting of SARS-CoV-2 virus particles with ultra-high sensitivity, and (2) Rapidly quantify SARS-CoV-2 virus particles in breath and on surface for POC diagnosis, and distinguish influenza virus from SARS-CoV-2 by multiplexed detection. This transformative diagnostic technology will possess ultrahigh sensitivity and specificity to detect SARS-CoV-2 viruses in exhaled air while in low cost and simple to use by any person. The use of CIER paper will not only immediately identify virus spreading people, but also save huge waste of resources to contain pandemic by a small percentage of contagious individuals.",2021,2023,N/A,196012,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15242,3P51OD011132-61S2,Developing an NHP model for understanding the biological causes of long COVID-19 pathogenesis,"Abstract As of April 30, 2021, the COVID-19 pandemic has resulted in more that 148 million cases and with 3.1 million deaths worldwide. Typically, people recover from COVID-19 after 2 to 6 weeks; however, in a significant fraction of patients symptoms may linger or recur for weeks or months following initial recovery. These ""long COVID-19"" symptoms or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) include fatigue or muscle weakness, sleep disorders, loss of taste or smell, confusion, anxiety, and depression. While the clinical characteristics and pathogenesis of acute COVID-19 disease are being intensively studied, the long-term consequences of disease remain largely unknown. Furthermore, the small number of PASC research studies published to date are limited by a relatively short follow-up after patients are discharged from the hospital; a lack of pre-infection data; and limited sampling of tissues. Here, taking advantage of a recently established nonhuman primate (NHP) model of SARS-CoV-2 infection, we aim to establish biosafety guidelines to validate and standardize PASC NHP studies in rhesus macaques- up to 18 weeks post-infection - in which animals repeatedly testing negative for SARS-CoV-2 will be transferred from ABSL-3 to ABSL-2+ facilities (Aim 1). This ability to transfer animals from ABSL-3 facilities will be critical to allow the study of PASC in NHP with acceptable costs and labor, while preserving the safety of personnel and the NHP colonies. Transfer of animals to BSL-2+ will allow us to characterize neurological and behavioral manifestations observed in human PASC. Additionally, we are proposing extensive and state-of-the-art immunologic and virologic analyses in a long-term study of SARS-CoV- 2-infected rhesus macaques (RMs) to define the pathogenesis and identify mechanisms underlying PASC (Aim 2). Importantly, our study will contribute to the establishment of NHP models of SARS-CoV-2 infection and could prove essential for understanding long-term effects of SARS-CoV-2 pathogenesis. This model provides longitudinal assessment of disease findings, pathogenesis, immune responses, and viral persistence. Furthermore, collection of multiple tissues virtually impossible to obtain in humans, such as gut, brain, heart and lung, will allow us to identify pulmonary and extra-pulmonary long-term and/or permanent damage. Finally, specimens collected longitudinally and at necropsy will be cryo-banked and will be key in bridging our discoveries with data compiled in SARS-CoV-2 recovery human cohorts. These studies will allow us to dissect biological causes underlying PASC, thus providing key insights for preventing and treating the effects of long-term COVID- 19 disease. The proposed studies are within the scope of the parent award and are highly likely to foster additional research funding leading to the progress of the overall goals of the parent award. However, there is no overlap with work already funded in the parent award.",2021,2022,N/A,499999,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Disease models | Disease pathogenesis | Supportive care, processes of care and management",2021 +C15243,1R01EB031510-01,A SARS-CoV-2 NFC ePAD Biosensor,"PROJECT SUMMARY The current SARS-CoV-2 outbreak has begun to reshape how we think about and use diagnostic assays for preventing the spread of infectious diseases. Early diagnostic efforts specific to SARS focused almost solely on detecting the virus using nucleic acid amplification tests; more recently detection of circulating antibodies using ELISA to complete serological screening. While these techniques can provide accurate results, they require laboratory facilities and equipment, creating a significant delay between sampling and results. Rapid diagnostic tests in the form of lateral flow assays have appeared more recently but so far have lacked the sensitivity and selectivity to be useful for slowing disease spread. Another challenge with current approaches is that they require different molecular approaches for different markers making creation of a single test that can determine if an individual is or has been infected is challenging. As a result, there is a clear and pressing need to develop a single sensing platform that can quantitatively detect ng/mL levels of both viral antigens produced during infection and circulating antibodies at the point-of-care from blood, saliva, or nasal swabs that can be used by essentially anyone with little or no training. The goal of this project is to create a simple, inexpensive, and deployable electrochemical paper-based analytical device (ePAD) for detecting SARS-CoV-2 antigens and antibodies in blood, saliva, and nasopharyngeal swabs. Our device will combine three innovative components: a label-free electrochemical biosensor, a disposable near field communication (NFC) potentiostat, and a self-powered microfluidic device that performs complex sample preparation steps without user intervention. This system, the NFC-ePAD, will allow a user to literally add sample and press a button on the sensor and then place their phone on the unit to initiate the measurement. The phone activates the sensor and reports the results to the user. To achieve our goal, we are collaborating with colleagues at Chulalongkorn University and Silicon Craft™ in Thailand. Our aims are 1) demonstrate a sensitive label-free biosensor for circulating SARS-CoV-2 nucleocapsid protein and anti-spike receptor binding domain (RBD) antibodies, 2) create a self-power microfluidic device for sample processing, and 3) validate the system using deidentified, banked clinical samples. Once developed, the system will provide a fast, simple, and easy-to-use platform for healthcare providers and individuals alike to rapidly determine the infection and immune status of potential COVID-19 patients.",2021,2023,N/A,988864,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas | South-East Asia,,,,,United States of America | Thailand,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2021 +C15244,1R01AI158775-01,Development of dual inhibitors targeting the viral main protease and the host cathepsin L as SARS-CoV-2 antivirals,"Project Summary The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. There is no vaccine or antiviral available for SARS-CoV-2. In this grant, we propose to develop dual inhibitors targeting viral main protease and cathepsin L as SARS-CoV-2 antivirals. Using the FRET-based enzymatic assay, we recently identified several inhibitors including boceprevir, GC-376, and calpain inhibitors II and XII, that have potent activity with single-digit to submicromolar IC50 values in the enzymatic assay. Significantly, all four compounds inhibit infectious SARS-CoV-2 replication in cell culture with EC50 values ranging from 0.5 to 3.4 µM. Overall, the compounds identified provide promising starting points for the further development of SARS-CoV-2 therapeutics. Our discovery of calpain inhibitor II as a potent inhibitor against SARS-CoV-2 is innovative as it suggests it might be feasible to develop SARS-CoV-2 antivirals by simultaneously targeting both viral Mpro and host cathepsin L, both of which are essential for viral replication. Compared to recently reported Mpro inhibitors, the hits identified from our study represent the most potent and selective drug candidates with a novel mechanism of action, therefore warranting further development. Given our encouraging preliminary data, we propose to optimize dual inhibitors as SARS-CoV-2 antivirals. The objective of this proposal is to develop dual inhibitors as potent SARS-CoV-2 antivirals with high potency, selectivity, favorable pharmacokinetic properties, as well as broad-spectrum antiviral activity against closely related coronaviruses such as SARS and Middle East respiratory syndrome (MERS) coronaviruses. Our goals of this grant are to identify additional dual inhibitors through both high-throughput screening and structure-based lead optimization of our recently identified dual inhibitors. By targeting the SARS-CoV-2 Mpro, the expected outcomes of the proposed research are broad-acting coronavirus antivirals with a confirmed mechanism of action, a high selectivity index, and favorable in vitro pharmacokinetic properties that are ready for in vivo antiviral efficacy testing in relevant animal models. Overall, this grant is based on strong preliminary data and our expertise in developing antivirals targeting cysteine proteases.",2021,2026,N/A,759766,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15245,1R21AI163816-01,Development and Evaluation of Novel Aptamer-based Therapeutics Targeting SARS-CoV-2 in a Physiologically-Relevant Model of Human Airway Epithelium,"The impact of SARS-CoV-2 on public health and the global economy cannot be overstated. As of September 28, 2020, 33,224,222 cases and 999,298 deaths worldwide have been linked to this emergent virus. This staggering number continues to grow, with the United States baring disproportionately high rates of morbidity and mortality. The virus targets the respiratory tract, leading to a wide range of clinical outcomes including mild upper respiratory tract illness and severe viral pneumonia with respiratory failure. To date, four SARS-CoV-2 vaccine candidates have entered phase 3 clinical trials and a massive parallel effort has been undertaken to repurpose already FDA-approved drugs for the treatment of COVID-19 or identify compounds with potential therapeutic activity. Despite this effort, remdesivir remains the only approved (with emergency use authorization) direct-acting antiviral for the treatment of COVID-19. Of critical importance: there is currently no vaccine or SARS-CoV-2-specific therapy approved for the prevention or treatment of disease. Furthermore, multiple antivirals may be required to avoid the rapid emergence of resistant SARS-CoV-2 strains. Thus, the development of novel therapeutics targeting SARS-CoV-2 are urgently needed. Infection requires interaction between the viral surface protein, spike (S), and a host protein, ACE2, that is expressed on type II alveolar cells and ciliated cells in the human airway epithelium (HAE), making these cells potentially vulnerable to infection. Thus, our goal is to develop a novel therapeutic that blocks this interaction between spike (on the virus) and ACE2 (on the host cell) to prevent infection and ameliorate disease. Aptamers are short nucleic acid-based sequences that bind with high affinity to their targets. Among other applications, aptamers have been shown to have potent antiviral activity and low toxicity in cell culture. While aptamers were originally made with RNA and DNA, Xeno-Nucleic Acids (XNA: nucleotide analogs with altered sugar, base, or phosphate backbones) have emerged as important new substrates and XNA aptamers often demonstrate enhanced target binding and greater stability compared to RNA and DNA aptamers. Thus, we hypothesize that aptamer technology, and specifically XNA aptamers, can be leveraged to inhibit spike-ACE2 interaction and propose to establish an innovative, in vitro screening platform that can serve to assess the efficacy of such aptamers, or other novel therapeutics, in blocking infection. This platform will utilize SARS-CoV-2 pseudoparticles (allowing work under Biosafety Level 2 containment) and a physiologically-relevant in vitro model of human airway epithelium that recapitulates the mucosal surface of the airway in vivo. Aptamers will also be tested using live virus infections of culture cells (Biosafety Level 3). This work is highly significant given the immediate need for novel therapeutics against SARS-CoV-2. Further, the development of a high-throughput, pseudoparticle-based assay to assess viral entry in a relevant culture system will have broad applications for additional drug screens and / or studies that aim to further understand SARSCoV- 2 virus-host interactions at the level of particle uptake.",2021,2023,N/A,231750,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15246,1R01AI158649-01,SARS-CoV-2 protease inhibitors for treating COVID-19,"Abstract The main objective of this project is to advance our extensive preliminary results and develop novel protease inhibitor drugs for the effective treatment of COVID-19. The COVID-19 pandemic, caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), emerged in central China's Hubei Province, Wuhan in December 2019. The outbreak has spread at an alarming rate, creating a catastrophic global health crisis the likes of which the world has not witnessed in over 100 years. SARS-CoV-2 has spread to nearly every continent around the globe and has affected over 4.8 million individuals with more than 380,000 deaths. Thus far, there are no vaccines or approved effective drug treatments against COVID-19. The development of antiviral agents is the foremost priority for reducing morbidity and mortality around the world. SARS-CoV-2 encodes two classes of cysteine proteases, the 3-chymotrypsin-like protease (3CLpro) and the papain-like protease (PLpro), which are critical for coronavirus replication. These two proteases have been recognized as important targets for drug development against COVID-19 and related pathogenic coronaviruses. In our extensive collaborative work against SARS and MERS coronaviruses, we previously developed and reported the development of a variety of covalent and non-covalent small- molecule reversible inhibitors of SARS-CoV-3CLpro that showed significant antiviral activity. We also demonstrated that PLpro is a significant drug target by developing the first non-covalent, reversible and potent inhibitors of SARS-CoV-PLpro that show effective antiviral activity in cell culture and in an animal model. We carried out structure-activity and extensive X-ray structural studies to gain molecular insight into the 3CLpro and PLpro active sites of SARS, MERS and most recently SARS-CoV-2. Furthermore, we have now generated a number of new small molecule lead inhibitors of SARS-CoV-2 3CLpro and PLpro and determined several high- resolution X-ray structures of SARS-CoV-2 3CLpro inhibitor complexes. This work forms the basis of our proposed studies. We now plan to design, optimize and develop structurally novel drug- like and broad-spectrum protease inhibitors that show favorable pharmacological profiles and low toxicity. We will carry out a multidisciplinary research effort that will integrate X-ray structure- guided design, iterative medicinal chemistry, molecular modeling, biochemical and biophysical assays, antivirus and cell biological studies in combination with various physiochemical assays to optimize compounds for preclinical development against COVID-19.",2021,2026,N/A,750974,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15247,3R01ES028615-07S1,Community-Engaged Covid-19 Interventions to Protect and Monitor Children,"PROJECT SUMMARY/ABSTRACT This Administrative Supplement will focus on low-income Black and Latinx children and their families in the Chicagoland metro area. Three reasons drive the need for this additional support. First, the newer COVID-19 variant strains have shown increased susceptibility for children. Second, COVID-19 vaccinations will soon be approved for children under the age of 16, making them the next target for vaccination efforts. Third, schools will be in person starting the fall of 2021, requiring frequent COVID-19 testing for children and their families. Our team has partnered with MobileCare Chicago and the Chicagoland COVID Collaborative to address these issues. MobileCare Chicago is a non-profit organization that provides clinical asthma and dental care using mobile medical clinics (vans) that rotate among schools in a predominantly low-income, minority populations on the south and west sides of Chicago. MobileCare Chicago has recently begun partnering with local health centers to leverage their mobile community facilities to distribute COVID-19 vaccination to adults. The Chicagoland COVID Collaborative is one of 21 National Institutes of Health (NIH) Community Engagement Research Alliance Against COVID-19 Disparities (CEAL) teams. Although led by the University of Illinois Chicago (UIC), the Chicagoland COVID Collaborative includes six other co-principal investigators and their institutions. This partnership of academic and community health disparities experts is working together to improve COVID-19 vaccination and engagement in quality therapeutic care and trials for low-income Black and Latinx communities in the Chicago area. Some of the lessons learned to date from earlier CEAL teams and the experiences of the Chicagoland COVID Collaborative are the importance of (1) locating COVID-19 vaccination services in community locations, and (2) using community health workers and other trusted messengers to spend time with individuals discussing their questions and concerns around vaccination, and providing accurate information and problem-solving support. Our proposed work with this supplement will co-locate COVID-19 testing with vaccination efforts directly at schools in low-income Black and Latinx communities in Chicago using the MobileCare Chicago network and clinical vans. Children, their families, community members, and school staff will all be offered COVID-19 testing and vaccination at their local schools. They will also be offered counseling and information on COVID-19 testing and vaccination from trusted staff at MobileCare Chicago. This proposed model leverages the lessons learned and infrastructure from the CEAL and RADx-UP programs to date to enhance both COVID-19 testing and vaccination.",2021,2022,University of Illinois Chicago,300000,Human Populations,Black | Other,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2020 +C15248,1R21ES032973-01,Environmental Factors Predicting Risk of Severe COVID Infection,"Project Summary/ Abstract The objective of this project is to identify the effect of air pollution on the risk and severity of COVID-19 illness. Air pollution may increase the risk of viral infections of the lung in general and there is emerging evidence that COVID-19 illness may be increased in regions where air pollution levels are high. Identification of factors that increase risk of COVID-19 illness will have major public health impacts. We will assess the incidence, prevalence and severity of COVID-19 infection within COPDGene, a well-characterized, longitudinal cohort of subjects with and without existing lung disease. The cohort is distributed at 20 clinical centers across the United States and includes subjects with a broad distribution of socioeconomic characteristics, rural and urban locations and air pollution exposures. The cohort was enriched for African-American subjects. We will adjust for other socioeconomic factors in the models using county level census data and normalize the cohort data to county level disease prevalence. Longitudinal analyses of COVID-19 incidence in relation to changing levels of monthly air pollution will be done and the impact of pre-existing lung disease on the outcomes will be studied. The air pollution data will be based on spatial analysis of the cohort using satellite and ground monitoring measures of particulates, NOx, SO2, CO and ozone, to identify factors that modify risk of: any disease, severe disease or death. The impact of air pollution on lung structural damage after COVID-19 illness will be measured using pre and post-COVID chest CT scans and spirometric changes in the cohort to identify extent of lung involvement and persistent effects.",2021,2023,N/A,242800,Human Populations,Black | Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15249,2P20GM113117-06,Host Substrate Profiling of SARS-CoV-2 Virus Protease,"PROJECT SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the viral pneumonia outbreak of coronavirus disease 2019 (COVID-19) causing widespread morbidity and mortality. Main protease (Mpro) encoded by SARS-CoV-2 processes the viral polyproteins and facilitates viral replication. Once activated, this enzyme can evade the host innate immune responses by cleaving host proteins. The host protein substrates of SARS-CoV-2 Mpro are not well characterized. The major challenges with the direct detection of host protein targets is their low abundance and technical limitations with the specificity and sensitivity of the current methods. Thus, this proposal is designed to develop a more specific and sensitive approach termed N-terminomics to discover unique protein fragments that are generated by Mpro during SARS CoV-2 infection. The Specific Aims of this proposal are: 1) Development and validation of novel probes to identify protease fragments generated by SARS-CoV-2 Mpro in cell lysate and 2) Identify and quantify the endogenous substrates of SARS-CoV-2 Mpro in infected mammalian cells. The rationale for the proposed research is that its success would facilitate a greater understanding of which host pathways are altered by this SARS-CoV-2 to cause a severe disease condition. Moreover, host targets of MPro can be used to develop treatment regimens to treat severe cases if COVID-19. The expected outcome of this research is that our approach will be more sensitive and readily adaptable for the host substrate profiling of any pathogenic proteases and it will aid in mapping cellular pathways which are hijacked by pathogens to invade the host system.",2021,2026,N/A,209821,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2016 +C15250,3UL1TR003167-03S3,Addressing COVID-19 Testing Disparities in Vulnerable Populations Using a Community JITAI (Just in Time Adaptive Intervention) Approach - Phase II,"ABSTRACT The (Phase goal of the Center for Clinical and Translational Science's (CCTS) proposed continuation II) RADx-UP 121 project is todetermine trends and disparities of SARS-CoV-2 testing, infections, and COVID-19 vaccination coverage in threetargeted Texas regions:Houston/Harris County; South Texas (Cameron and Hidalgo Counties; and 3) Northeast TX (seven counties including the city of Tyler). This effort will result in improved and expanded time related will: recent structural and access enabled multilevel, just-in- adaptive intervention trategies to reach vulnerable populations experiencing inequities to COVID-19. More specifically, in collaboration with community partners, this project 1) identify disparities and dynamics of SARS-CoV-2 testing and infections, considering data on COVID-19 vaccination; 2) identify personal, organizational, community, and factors contributing to SARS-CoV-2 testing and COVID-19 vaccination disparities, 3) expand the reach and impact of a multil evel intervention to increase motivation for and to testing and vaccination among vulnerable populations. The project's efforts will be by leveraging long-standing community partnerships. s Phase II will be informed by learnings and accomplishments from the Phase I effort, which have included: (1) Developing real-time data processing procedures and implemented quality control measures for various local data, including SARS-CoV-2 testing data, case investigation and hospital records; (2) Processing and analyzing COVID-19 case data including over 367,000 cases in Harris County, over 40,000 in Cameron County, and over 29,000 cases in Northeast Texas counties - all datasets now have common data elements and consistent formats; (3) Developing several metrics to quantify the COVID-19 disease burden for the overall population and by demographic subgroups; (4) Developing the census block group (CBG)-level disparity index, which is constructed using 12 variables from the American Community Survey (ACS) and; (5) Identifying the CBGs disproportionately affected by SARS-CoV-2 infections and prioritizing them for interventions to increase testing uptake and COVID-19 vaccination using the developed disease burden metrics and disparity index. Changes (enhancements and expansion) to be implemented in Phase II, as compared to Phase I (benchmark), include: (A) Adapting Phase I CHW-training/outreach program to include training on motivational interviewing, and an expanded focus on vaccination education and motivation/promotion of testing; (B) Enhancing 2-1-1-based education, motivation, and referral to testing and vaccination, (C) Including broader-based social media outreach, such as geo- targeted Facebook ads to motivate users to access COVID-19 testing and vaccination; (D) Conducting a panel study to compare the effectiveness of the CHW-Facilitated Self-Sampling Intervention vs. CHW Testing Navigation Intervention on participation in SARS-CoV-2 testing, and; (E) Assessing the impact and reach of multilevel COVID-19 communication networks on individuals' attitudes, intentions, and decisions on behavior surrounding SARS-CoV-2 testing and COVID-19 vaccination in underserved communities.",2021,2023,N/A,1174131,Human Populations,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15251,1R21AI160030-01A1,De Novo Designed Protein Nanoparticle Agonists Targeting the Tie2 Receptor for the Treatment of ARDS and Sepsis in Patients with COVID-19,"Broader Impacts: The current COVID-19 outbreak is a global pandemic with over 45 million cases and 1,200,000 deaths officially reported. Epidemiological data emerging from Italy indicate that 40-96% of COVID- 19 patients admitted into the hospital develop ARDS and sepsis. Developing a functional treatment for these conditions would also have far reaching impacts beyond this current pandemic, as the underlying pathology can arise from a multitude of factors. Overview: The goal of this project is to engineer a Tie2 super-agonistic nanoparticle (NP) and optimize its production at large scale. Our NPs would be used to treat the lethal symptoms of the current COVID-19 viral outbreak. Acute respiratory distress syndrome (ARDS) and sepsis are major contributors to COVID-19 mortality. Currently there are no approved drugs to treat these conditions, because activation of the target receptors cannot be controlled. To bypass these limitations, we engineered a de novo protein therapeutic that overcomes the major limitations of manufacturing and rapid regeneration of vascular tissue needed to treat ARDS and sepsis. Such a technology could mitigate the dangers of COVID infection when patients enter clinics or quarantine. Our NP super-agonist overcomes the limitations of Ang1, the natural protein that signals through Tie2, which is too unstable to be used as an effective treatment for ARDS or sepsis. The proposed funding would allow for immediate development of the NP to improve bioavailability and validation of therapeutic utility in two murine infection models. We will achieve this in three separate aims: Aim 1: Measure PK/PD, Toxicity and Immunogenicity of Pegylated Ang1F-NP In Vivo. Aim 2: Validate In Vivo Efficacy of Ang1F NPs in C57Bl/6 mice infected with H1N1-PR8. Aim 3: Validate Whether Ang1-NPs Reduce Lung Injury in Murine COVID-19/SARS- CoV-2 Infection. Intellectual Merit: We aim to develop experimental and technological advances that will have a strong impact in the fields of structural biology, therapeutic discovery, and clinical medicine. We are working with one of the few medical branches that have access to the current COVID-19 strain and who are actively developing animal models to test out therapies prior to clinical trials. The proposed research could be a key solution to reduce the total number of deaths and enable healthcare professionals to better treat patients suffering from viral outbreaks.",2021,2023,N/A,308875,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15252,1U01AG076557-01,"A New Database to Measure the Association Between Income, Race, and Mortality: Inequality in Longevity During and Beyond the COVID-19 Pandemic","OTHER PROJECT INFORMATION - Project Summary/Abstract A New Database to Measure the Association Between Income, Race, and Mortality: Inequality in Longevity During and Beyond the COVID-19 Pandemic Disparities in health and life expectancy by income are a central challenge for the United States. The highest- income American men live nearly 15 years longer on average than the lowest-income American men; the corresponding gap for women is 10 years. The COVID-19 pandemic has amplified these disparities by income, race, and other dimensions. Unfortunately, we currently lack information on how mortality rates due to COVID- 19 vary with individual income, because available U.S. population mortality data lacks information on income. The absence of this information has hindered our ability to monitor the impacts of COVID-19 and develop policies to mitigate its impacts, particularly on disadvantaged and underserved populations, going forward. This project will resolve these challenges by constructing a new public database of mortality rates incorporating socioeconomic and demographic variables and covering the entire U.S. population. Using these data, researchers will be able to analyze the sources of disparate impacts of COVID-19 on mortality across subgroups, with the aim of understanding how to reduce health inequality in the pandemic and beyond. The project has three specific aims. Aim 1 of this project is to release a new public database of mortality rates by age, income, race/ethnicity, gender and county, and provide recurring annual updates to this database. This database will be constructed by linking from tax returns, the decennial Census, and Social Security death records. Aim 2 will characterize the short-term effects of the COVID-19 pandemic on mortality rates by race and income in 2020- 21. This analysis will measure the quantity of excess deaths and disparities in their distribution caused by the pandemic, and identify economic and health mechanisms generating those disparities. Aim 3 will measure the long-term effects of post-pandemic changes in health, health behaviors, labor income, tax and transfer policies, and behaviors on racial and socioeconomic inequality in mortality. This broader set of analyses will use the substantial disruptions generated by the pandemic to examine how and why disparities are growing or shrinking over time. Taken together, this project will contribute to research and policy work by providing critical new data on the relationship between socioeconomic status and health, thereby providing a tool to monitor progress in mitigating the impacts of the COVID-19 pandemic in underserved communities.",2021,2026,N/A,656834,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C15253,3R01ES030353-03S1,Environmental and Social Health Determinants of Pregnancy Outcomes Related to COVID-19 Pandemic,"The COVID-19 pandemic is uniquely challenging for pregnant women. Adverse pregnancy outcomes (e.g. gestational diabetes, pre-eclampsia & eclampsia, preterm birth, antepartum depression, and postpartum depression) are likely worsened by the COVID-19 pandemic. A few recent studies have shown that ambient fine particulate matter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2) may increase the susceptibility to SARS- CoV-2 infection, severity of illness, and mortality in the general population. It is reasonable to hypothesize that ambient air pollution may likely increase the risk of adverse pregnancy outcomes related to COVID-19 pandemic. But the effect of air pollution coupled with maternal comorbidities and sociodemographic determinants on adverse pregnancy outcomes related to COVID-19 pandemic has not been established. This time-sensitive competing revision will extend the scope of the parent study of Air Pollution and Pregnancy Complications in Complex Urban Environments: Risks, Heterogeneity, and Mechanisms (R01ES030353) by examining associations of air pollution with major adverse maternal outcomes related to COVID-19 pandemic among the large diverse pregnant women population from the electronic health record database of Kaiser Permanente Southern California (Aim 1), and further studying the role of SARS-CoV-2 infection, preexisting comorbidity, and sociodemographic factors on these associations (Aim 2). We have a multi-disciplinary team with expertise in environmental exposure assessment, environmental epidemiology, maternal-fetal medicine, and biostatistics to examine the specific aims. To our knowledge, this is the first study to determine the association of air pollution with adverse pregnancy outcomes related to COVID-19 pandemic. The proposed study has several major innovations and methodological strengths, including 1) large (67,000 deliveries during the COVID-19 pandemic and 45,000 deliveries before the pandemic) and diverse population (the majority from racial and ethnic minority groups); 2) high quality, prospectively-recorded, and time-resolved individual-level clinical data for both outcomes and potential effect modifiers, including COVID-19 case data based on universal screening of pregnant women; 3) investigation associations between air pollution exposure and antepartum and postpartum depression; 4) analysis of effect modification by SARS-CoV-2 infection, comorbidity, and sociodemographic factors; 5) high spatiotemporal resolution PM2.5 exposure estimates based on dense ground-level senor network data; and 6) thorough examination of potential confounding from individual-level maternal factors (e.g. smoking, physical activity) and other environment exposures (e.g. heatwave and green space). This study will generate new knowledge about the impact of air pollution on adverse maternal outcomes related to COVID-19 pandemic. As air pollution is a modifiable risk factor, this study can help advance interventions to reduce the adverse pregnancy outcomes related to COVID-19 pandemic.",2021,2022,N/A,771695,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15254,1R01AI159946-01A1,Multi-Dimensional Outcome Prediction Algorithm for Hospitalized COVID-19 Patients,"PROJECT SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated coronavirus disease (COVID-19) is an evolutionarily unprecedented natural experiment that causes major changes to the host immune system. Several high risk COVID-19 populations have been identified. Older adults, males, persons of color, and those with certain underlying health conditions (e.g., diabetes mellitus, obesity, etc.) are at higher risk for severe disease from COVID-19. While it is too soon to fully understand the impact of COVID-19 on overall health and well-being, there are already several reports of significant sequelae, which appear to correlate with disease severity. There is a clear and urgent need to develop prediction tests for adverse short- and long-term outcomes, especially for high-risk COVID-19 populations. We hypothesize that complementary multi-dimensional information gathered near the time of symptom onset can be used to predict new onset or worsening frailty, organ dysfunction and death within one year after COVID-19 onset. A single parameter provides limited information and is incapable of adequately characterizing the complex biological responses in symptomatic COVID-19 to predict outcome. Since they were designed for other illnesses, it is unlikely that existing clinical tools, such as respiratory, cardiovascular, and other organ function assessment scores, will precisely assess the long-term prognosis of this novel disease. Our extensive experience in biomarker development suggests that integrating molecular and clinical data increases prediction accuracy of long-term outcomes. We have chosen to test our hypothesis in a population reflecting US-demographics that is at increased risk of adverse outcomes from COVID-19. We will enroll patients, broadly reflecting US demographics, from a hospitalized civilian population in one of the country's largest metropolitan areas and a representative National Veteran's population. We anticipate that a prediction test that performs well in this hospitalized patient group will: help guide triaging and treatment decisions and, therefore, reduce morbidity and mortality rates, enhance patient quality of life, and improve healthcare cost-effectiveness. More accurate prognostic information will also assist clinicians in framing goals of care discussions in situations of likely futility and assist patients and families in this decision-making process. Finally, it will provide a logical means for allocating resources in short supply, such as ventilators or therapeutics with limited availability.",2021,2026,N/A,747559,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity,2021 +C15255,3U19AG063893-03S2,The Long Life Family Study,"Abstract The Long Life Family Study (LLFS) is a cohort of unusually healthy individuals who show longer health spans and marked delays in the onset of dementia, heart disease and stroke. The LLFS participants also show enrichment in Healthy Aging Phenotypes (HAPs) that include several biological domains such as exceptional memory, grip strength, pulmonary function, blood pressure, and/or metabolism. Since LLFS recruited families showing familial clustering of longevity, even the younger participants may have protective factors that give them increased probability of obtaining exceptional longevity themselves. However, exposure to the SARS-CoV-2 virus may quite possibly be an important risk/protective factor determinant of future health for the LLFS participants. In particular, evidence suggests there may be long term increased CVD risk such as myocarditis and stroke or cognitive impairment in affected survivors. This proposal seeks to augment the existing strengths of LLFS, which include longitudinal detailed phenotyping and serial multi-omics assays to identify risk for various health outcomes by conducting an antibody test for exposure to the SARS-CoV-2 and help classify LLFS participants as symptomatic individuals diagnosed with COVID-19 infection, asymptomatic carriers of COVID- 19 infection, as well as those who did not have COVID-19 infection or the disease. Till date, SARS-CoV-2 antibody studies have focused almost exclusively on blood based antibody responses and mucosal immunity in the naso- and oro-pharyngeal areas, the primary sites of SARS-CoV-2 infection, remain poorly understood. Hence, this study will measure SARS-CoV-2 antibodies in saliva to minimize risk to participants and provide an estimate of mucosal immunity in this population. Specifically, this administrative supplement will measure different isotypes of SARS-CoV-2 antibodies (IgG and IgA) in saliva (Aim 1) and also measure quantitative levels of both these antibody isotypes (Aim 2). We will accomplish both aims by using a self collected saliva sample analyzed using an in-house SARS-CoV-2 ELISA assay and a commercially available FDA-EUA approved assay (Roche Inc.) that will be able to differentiate between SARS-CoV-2 antibodies produced due to natural infection or vaccination. We will use family based multivariate generalized linear models to test for associations of SARS- CoV-2 antibodies (isotypes and quantitative levels) with both aging trajectories as well as with subsequent follow- up data on morbidity and mortality. This approach will allow us to estimate the independent contribution of SARS-CoV-2 antibodies to outcomes of interest, after controlling for other, known risk factors and measures (including various OMICs). Thus, identifying LLFS participants who were exposed to SARS-CoV-2 infection will provide an opportunity to evaluate the effect of SARS-CoV-2 infection on the trajectories of several HAPs that are enriched in LLFS, future health events and overall health span of LLFS participants.",2021,2024,N/A,509767,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Immunity,2019 +C15256,3U54MD002316-15S2,Eliminating COVID-19 disparities in partnership with underserved/vulnerable transnational communities of Arizona,"Project Summary/Abstract The COVID-19 pandemic significantly affects the entire State of Arizona but impacts communities along the border with Mexico disproportionally. Majority Latinx and American Indian communities along this border have higher infection rates and less access to testing and vaccination. This proposed supplement aims to increase access to testing and related services for these underserved transnational communities. The expansion of our current community-driven and culturally congruent project will advance knowledge about barriers to care and effective strategies to increase testing and vaccination in the border region. This application extends the work of ASU's health disparities U54 center grant (RFA-MD-17-005; 5U54MD002316) and its RADx-UP supplement (3U54MD002316-14S1) by reducing disparities in COVID-19 diagnostics, vaccination, education, wraparound services and health care, with the goal of improving the health of vulnerable and underserved communities. The aims of this emergency competitive revision closely match and enhance the aims of the current U54 award and its RADx-UP supplement. The focus on populations along the AZ-Mexico border will add to existing knowledge about assets and vulnerabilities of diverse transnational communities disproportionally affected by the pandemic. The approach empowers local communities, is data driven, and creates the infrastructure capacity for community-driven delivery of care. Following a Community Based Participatory Research (CBPR) orientation, the revised supplement expands our existing R.A.P.I.D. program by improving access and decreasing hesitancy to COVID-19 testing and vaccination among underserved and vulnerable populations in the border region. Equality Health Foundation (EHF) will continue to serve as the lead community partner for the proposed revised supplement and the ASU Biodesign Clinical Testing Laboratory (ABCTL) will provide and analyze the saliva-based polymerase chain reaction (PCR) testing for SARS-CoV-2. Local partners coordinated by EHF under the One Community Initiative against COVID-19 will implement the vaccination program. Over two years, the revised supplement aims to reach 7,000 additional community members living and working along the AZ-Mexico border. CDCC surveys from border communities will be added to the ongoing longitudinal study we are conducting to assess the intervention's impact and also by comparing randomly selected participants (N=200) with a matched comparison group (N=200) randomly selected from regular testing sites. We will also conduct ongoing COVID-19 variants sequence validation among those tested and inform appropriate health authorities if significant variants emerge. The transdisciplinary team has the infrastructure, capacity, and community partnerships in place to implement the project effectively and efficiently. ASU's existing NIMHD-funded U54 center, guided by its Community and Scientific Advisory Board and in collaboration with government agencies, tribal governments, community organizations, and academic units within ASU, is well equipped to undertake the proposed revised supplement.",2021,2023,N/A,996702,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Community engagement | Vaccine/Therapeutic/ treatment hesitancy",2007 +C15257,3U01HL146203-03S1,Innovation Fund Application to the Multicenter AIDS Cohort Study (MACS)/Womens Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS): COVID-19 Vaccine Acceptance and Hesitancy (CVHB),"COVID Vaccine Study Supplement to MWCCS Principal Investigators: C. Rinaldo and J. Martinson Innovation Fund Application to the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS): COVID-19 Vaccine Acceptance and Hesitancy (CVHB) Study in People with HIV Abstract and Specific Aims MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV-infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative for their health that they be vaccinated with the new COVID-19 vaccines. To date, however, there are only anecdotal data on COVID-19 vaccine acceptance and efficacy in people with HIV (PWH). The MWCCS is ideal for analyzing (a) the acceptancy and effects of COVID-19 vaccine(s) in male and female PWH and matched HIV-uninfected controls (HUC), (b) the impact of age and co-morbidities on vaccine immune response and protection against COVID-19, and (c) the social, economic, and behavioral changes after COVID-19 immunization as compared to the individuals who opted to not take the vaccine. To address this issue, we will have 2 groups of MWCCS participants in this study: Group A: Male and female PWH and HUC who choose to receive a COVID-19 vaccine, Group B: Male and female PWH and HUC who choose NOT to receive a COVID-19 vaccine. The aims of our proposed longitudinal observational study for this OAR Innovation application are: Aim 1: To conduct an MWCCS-wide, mixed- methods investigation of the prevalence, correlates, and nuances of COVID-19 vaccine hesitancy among MWCCS participants. Results will help better understand the concerns of PWH and HUC populations regarding COVID-19 vaccines based on age, sex, race/ethnicity, and underlying comormidity burden. Aim 2: To determine the incidence of natural SARS-CoV-2 infections post-COVID-19 immunization in PWH as compared to HUC of the same age, sex, and ethnicity/race and also compare with the incidence of infections in non-vaccinated individuals. Because of budgetary limitations in the OAR Innovation Fund supplement, we will restrict Aim 2 to obtaining one specimen at baseline, just prior vaccination in Group A, and within comparable time periods for Group B. Subsequent samples collected during the core MWCCS visits will be used in the serological analyzes. These samples will allow us to determine the serological COVID-19 status pre-immunization, and post-immunization seroconversions for S and N proteins. The titration of anti-S responses post immunization will indicate vaccine immune response, while anti-N antibody titers will indicate natural SARS-CoV-2 infection This information will allow the identification of asymptomatic and symptomatic individuals infected with SARS- CoV-2 post-vaccination and in non-vaccinated group. The if these infections in the MWCCS will allow a targeted use of core samples in depth investigation of the immune mechanisms of vaccine-mediated protection, the immunologic responses and virologic characteristics of breakthrough SARS-CoV-2 infections, and the impact of the vaccination on underlying HIV infection. Importantly, timely funding from this OAR Innovation opportunity is critical to our addressing these aims prior to the broad rollout of the COVID-19 vaccines to our PWH participants. We are in a race to obtain this critical information and specimens prior to the wide availability of current FDA EUA vaccines to our MWCCS participants. The MWCCS clinical research sites across the United States and the data center are ready to launch this new study as soon as funding is available and we receive sIRB approval.",2021,2026,N/A,33764,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Characterisation of vaccine-induced immunity | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15258,3R21TW011273-02S1,Building Capacity to Study the Intersection Between COVID-19 and HIV-Related Stigma among Adolescents in Western Kenya,"Project Summary/Abstract Kenya has one of the world's largest HIV and AIDS epidemics, with about 1.6 million people living with HIV and 25,000 people dying from AIDS in 2018. Adolescents, especially girls, are particularly vulnerable to HIV. In western Kenya, over 50% of adolescents had sexual intercourse before the age of 18; however, youth between the ages of 15-19 have low rates of condom use and HIV testing. Stigma negatively affects HIV prevention behaviors, including condom use and HIV testing. In Kenya, complex interactions between social capital, religiosity, and gender norms shape societies' discriminating attitudes towards youth perceived to be infected with HIV (i.e., HIV-related stigma), which, in turn, affects HIV prevention. Our parent award aims to study the relationship between social capital, religiosity, gender norms, and HIV-related stigma among adolescents (ages 15-19) and its impact on HIV prevention in western Kenya. With the advent of the COVID-19 pandemic, the Kenyan government enacted mitigation strategies, including lockdowns. Although these policies are important to limit the spread of COVID-19, they have many unintended consequences among adolescents, such as increased risk of HIV. Additionally, people living with HIV have increased psychosocial burdens emanating from stress, isolation, and stigma due to COVID-19. These outcomes are compounded by a lack of social relationships, especially among youth. Therefore, this supplement will use a mixed-methods approach to assess the effects of COVID-19 mitigation measures on changes in social relationships (i.e., social capital, religiosity, gender norms), stigma, and HIV prevention among youth in western Kenya by addressing the following specific aims: (1) Examine trends in social capital, religiosity, gender norms, stigma, and HIV preventive behaviors before and after the COVID-19 lockdown among adolescents in western Kenya; and (2) Elucidate the drivers of change in social relationships, the experience of stigma, and the changes in HIV preventive behaviors during the COVID-19 lockdown in western Kenya. In Aim 1, we will employ two surveys to explore social relationships, stigma, and HIV prevention among 765 boys and girls ages 15-19 years. The two surveys will ask youth to recall their experiences and perceptions before and during the COVID-19 pandemic. In Aim 2, we will conduct 18 focus groups discussions with boys and girls ages 15-19 years, healthcare providers, parents, teachers, and religious leaders to explore their perceptions of how COVID-19 has changed the lives of young people, especially youth living with HIV. This supplement will illuminate the unintended consequences of COVID-19 disease control efforts in relation to HIV preventive behaviors among adolescents in Kenya. Additionally, this study will extend research capacity at Tangaza University College and Gynocare Women's and Fistulas Hospital around studying the intersection between COVID-19 disease control efforts, stigma, and HIV prevention in Kenya.",2021,2022,Tangaza University College and Gynocare Women?s and Fistulas Hospital,110589,Human Populations,Black,Adolescent (13 years to 17 years),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Africa,Africa,,,,Kenya,Kenya,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts | Social impacts,2020 +C15259,1R01DK130377-01,The Untranslated 3'End of SARS-CoV-2 RNA as a Determinant of Obesity-Accelerated Infectivity,"Project Summary/Abstract Obesity is an epidemic-scale problem in the U.S. affecting about 35% of the adult population, and is a major risk factor for the ongoing pandemic, COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA betacoronavirus that is the causative agent of COVID-19. Despite rapid progress in developing effective vaccines, progress in devising improved therapeutics has been slow, and there is an urgent need for anti-viral therapeutics for treatment of infected patients not protected by vaccines. Certain demographics are variably resistant to vaccination, for example, obesity markedly reduces effectiveness of several vaccines. Therapeutics can also be critical in the eventuality that mutations in the virus render the vaccine ineffective. The molecular events responsible for expression of SARS-CoV-2 proteins are known from studies of other betacoronaviruses; however, the regulatory pathways and pathological conditions determining their expression are poorly understood. The translation of viral RNA utilizes the host mRNA translation machinery, primarily regulated by specific RNA-binding proteins or complexes that bind sequence or structural elements in terminal non-coding regions. Importantly, the coding regions of SARS-CoV-2 genomic RNA and the ten subgenomic mRNAs (sgmRNAs) are likewise bordered by non-coding upstream and downstream regions, termed the 5'- leader and 3'-end sequences, respectively. A critical feature of the genome and the sgmRNAs of SARS-CoV-2 is that identical 5'-leader and 3'-end sequences are present in all. Thus, the terminal sequences represent novel, unexplored targets for interference with virus assembly and function. We have discovered a 39-nt sequence in the 3'-end of SARS-CoV-2 bearing structural similarity to the GAIT (interferon-gamma-activated inhibitor of translation) RNA element previously described by us. We show that glutamyl-prolyl tRNA synthetase (EPRS) a protein that binds the human GAIT element also binds the vGLE. Moreover, IFN-γ, a pro-inflammatory cytokine, and insulin, an obesity-induced hormone, markedly increases expression of a luciferase reporter bearing the intact vGLE. These results are the first to show a functional consequence of an RNA element in the 3'-end sequence of SARS-CoV-2. We hypothesize that binding of EPRS to the vGLE stimulates sgmRNA translation required for expression of structural and other SARS-CoV-2 proteins, and for programmed ribosomal frameshifting required for genome replication. We will test this hypothesis by pursuing two Specific Aims: In Aim 1 we elucidate the role of EPRS binding to the SARS-CoV-2 3'UTR vGLE in regulating viral replication and sgmRNA translation. In Aim 2 we develop RNA inhibitors that target EPRS/vGLE interactions and block viral protein expression. We anticipate these fundamental studies will provide the first information on the function of the 3'-end of SARS-CoV-2, and will provide a foundation for development of therapeutic agents to be used in combination with mechanistically distinct anti-viral agents targeting the vGLE and possibly emerging betacoronaviruses.",2021,2024,N/A,402500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C15260,3R01CA189806-07S1,Impact of malaria on shaping immunity to EBV in the etiology of Burkitt lymphoma,"This administrative supplement is in response to NOT-CA-21-033 and aims to investigate the impact of the COVID-19 pandemic on Kenyan children diagnosed with endemic Burkitt lymphoma (eBL). The parent R01 CA189806-06 investigates malaria-induced immunoregulatory mechanisms that influence T cell cytotoxicity against EBV-infected B cells and eBL tumors. Kenyan children diagnosed with eBL and a cohort of healthy are being followed longitudinally to test the parent study objectives. The timely addition of COVID-related studies will determine the impact of COVID-19 public health protocols put into place by the Kenyan government in April 2020, on access to care and overall survival for Kenyan children with eBL. The supplemental activities include: 1) implementing a Knowledge, Attitude and Practices (KAP) psychosocial survey to ask parents of children enrolled in our study about COVID-19 and COVID-19 vaccines in order to assess barriers to prompt diagnosis, out-patient treatment compliance and research study participation; 2) SARS-CoV-2 monthly serosurveys which are easily added to our existing multiplex Luminex seroprofiling assay that has been validated by Dr. Moormann's NCI SeroNet partnership (NIH/NCI 1U01 CA261276-01) with the Frederick National Laboratory standards; 3) SARS-CoV-2 molecular testing to compare variants that infect cancer patients compared to healthy age-matched controls and which may have implications for vaccine efficacy; 4) testing the use of innovative and low-cost digital health technologies to monitor health metrics (skin temperature, breathing and heart rate, etc) of eBL patients during the course of their care when they are out- patients; 5) community engagement activities such as key-informant interviews and focus group discussions to learn more about the impact of the COVID-19 pandemic on cancer prevention and control programs that are well established in Kenya. The immediate outcomes from this supplemental study will be achieved within the year. We will determine how the COVID-19 public health measures have inadvertently impacted health-care access specific to cancer diagnosis and eBL survivorship. With community advice, we will implement strategies to overcome these obstacles, including exploring sustainable use of remote sensing, digital medicine technologies to monitor cancer recovery. If children in our study have been infected with SARS-CoV-2, then we will include this as a cofactor when testing the mechanistic objectives pertaining to immune regulation proposed in the parent study. We do not believe that SARS-CoV-2 will increase the incidence of eBL; however, we are still learning what this virus is capable of and its prolonged effects on multiple organs. In addition, our study will assess COVID-19 variants and vaccine efficacy for eBL patients compared to healthy children. COVID-19 vaccines were introduced in Kenya during March 2021 and we anticipate childhood vaccinations will be recommended to stop the pandemic. This is of concern for immunocompromised cancer patients, who may require a booster to achieve immune protection against SARS-CoV-2.",2021,2025,N/A,158208,Human Populations,Black,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Africa,,,,,Kenya,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Prognostic factors for disease severity | Indirect health impacts,2014 +C15261,1R21DA053164-01,"Investigating the Impact of Substance Use, Intimate Partner Violence, and COVID-19 on HIV Care Engagement among Young Black Sexual Minority Men with HIV in the US South","SUMMARY/ABSTRACT Among sexual minority men, young Black sexual minority men are the most disproportionately impacted by HIV, with the majority of new infections among sexual minority men occurring among this group. Intimate partner violence (IPV) is one of the most understudied factors that may exacerbate these disparities. Little is known about the impact of substance use and IPV on HIV care continuum (CC) outcomes and HIV transmission risk behaviors among young Black sexual minority men with HIV (YBSMM+). Both IPV and substance use leading to IPV may help explain poorer CC engagement among YBSMM+ and are likely to be exacerbated by the COVID-19 pandemic, which is having devastating health and economic impacts. The COVID-19 pandemic is also likely to interfere with CC engagement and viral suppression. The research that we propose is designed to overcome these gaps and limitations, and to identify modifiable intervention targets for strengthening the CC during times of acute psychosocial and economic stress. We propose to use existing data and to collect new data from the United Black Element+ project (UBE+; R01 MH102171). We will use structural equation modeling to explore the associations between substance use and IPV and their impact on HIV care engagement, viral suppression, condomless anal sex, and to determine if distinct forms of resilience (global resiliency, coping skills, and social support) buffer associations between these relationships among YBSMM+ in the U.S. South. This study can shed new light on the associations between substance use, IPV and CC outcomes and risk and will support the submission of an intervention development grant (R34) to develop a resiliency and advocacy-based intervention that reduces the impact of substance use and IPV on CC engagement and retention among YBSMM+. The project's focus on the role that resiliency factors may play in moderating harmful effects of substance abuse and IPV among YBSMM+ is innovative. This research can inform the development and adaptation of substance use, IPV, and CC interventions for YBSMM+.",2021,2023,N/A,231383,Human Populations,Black,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Gender,,,,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C15262,1R01AI161085-01,Small Molecule Inhibitors Against 3C-Like Protease of SARS-CoV-2,"PROJECT SUMMARY Human coronaviruses generally cause the common cold, a mild upper respiratory illness, however, global outbreaks of new human coronavirus infections with severe respiratory disease have periodically emerged from animals. These include Severe Acute Respiratory coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and, most recently, SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). Currently, there are no licensed vaccines or antiviral drugs against these viruses, underscoring an urgent need for the development of preventive and therapeutic measures against coronaviruses. Coronavirus genomes encode large polyproteins which are processed by a 3C-like protease (3CLpro) and a papain-like protease. Both proteases are essential for viral replication, making them attractive targets for drug development. Our foray in this area has resulted in the discovery of broad-spectrum inhibitors of multiple viruses, including coronaviruses and noroviruses that encode 3CLpro, as well as the first demonstration of clinical efficacy by a feline coronavirus 3CLpro inhibitor. Recently, we have demonstrated that a dipeptidyl series of compounds potently inhibit human coronaviruses, including MERS-CoV and SARS-CoV-2 in cell culture, and display in vivo efficacy in the DPP4-KI mouse model of MERS-CoV infection. The antiviral target of the compounds was validated by obtaining high resolution crystal structures 3CLpro-inhibitor complexes from SARS-CoV, SARS- CoV-2 and MERS-CoV. We hypothesize herein that the identified series can serve as a launching pad for the development of SARS-CoV-2-specific antivirals. The immediate and overarching goal of the proposed studies is to further optimize the pharmacological activity PK parameters of identified lead inhibitors of SARS-CoV-2 3CLpro and the demonstration of in vivo efficacy against SARS-CoV-2. The expected outcome of our studies is the selection of a preclinical candidate (and 1-2 backup compounds) that is well-suited to conducting further preclinical studies, ultimately leading to the development of a COVID-19-specific antiviral therapeutic.",2021,2026,N/A,774037,Other,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15263,1R01AI166358-01,The impact of T cell selection on vaccine durability,"Project Summary An ongoing outbreak of a novel coronavirus infection (COVID-19) has claimed millions of lives and disrupted social infrastructures around the world. Fortunately, the new mRNA vaccines from Moderna or Pfizer/BioNTech are highly effective against SARS-CoV-2. However, much remains unknown about the longevity of memory responses generated by the new mRNA-based vaccine platform in humans. With the emergence of new viral variants, there is also the need to have a flexible type of immunologic memory that is not only long-lasting but can also respond to mutated viruses. My lab studies human T cell memory. We have shown that the human pre-immune T cell repertoire for a novel pathogen is shaped by past antigen experiences and contains cross- reactive memory T cells that could compete with naïve T cells. Using a highly effective live attenuated yellow fever virus (YFV) vaccine as a model for novel infectious challenge, we tested how pre-immune repertoire impacts post-vaccine response. Multiple YFV-specific populations were identified longitudinally within the same individual using peptide-MHC (pMHC) tetramers. Extensive single-cell T cell receptor (TCR) sequencing on tetramer+ cells was used to follow progenies of the same parent cells over time. We found that vaccine selectively recruits initially rare but more responsive T cells, leading to better repertoire fitness and higher TCR diversity after vaccination. Having a diverse TCR repertoire has been directly linked to protective T cell responses and host survival in mice. For fast evolving pathogens, the diversity in T cell composition may additionally limit escape variants as mutations emerge. Here, we will use the mRNA vaccines for COVID-19 (COVID vaccines) as a model to study the durability and the breadth of T cell responses elicited by mRNA- based vaccine strategies. We hypothesize that effective peripheral T cell selection is critical for maintaining durable immunity against actively mutating viruses. Here we will build on established biological insights, resources, and donor recruitment infrastructures to determine: (1) if COVID vaccine drives effective repertoire selection and diversification, (2) how boosting enhances CD4+ T cell diversity and variant recognition, and (3) how post-vaccine memory cells are maintained and change with time. The proposed experiments will map the entire trajectory of vaccine-induced response using precise molecular and cellular tools. Data from this study will provide vital knowledge on the quality, the breadth, and the longevity of CD4+ T cell response to the mRNA vaccines in humans. Beyond COVID, insights revealed by the proposed research will be relevant for understanding how immunological memory is generated and preserved. The proposed research will therefore have broad impact and could aid future development of improved vaccine strategies for other pathogens.",2021,2026,N/A,658748,Viruses | Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +C15264,1U01HL158759-01,The effect of SARS-CoV-2 on the susceptibility of respiratory outcomes in a Puerto Rican Birth Cohort,"PROJECT SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The lack of diagnostic tests and current public health policies limit our knowledge of the true prevalence of SARS- CoV-2. Infection with SARS-CoV-2 results in production of anti-viral antibodies in infected hosts, yet it is currently unknown whether these antibody responses are protective against subsequent infection. Survivors of the 2003 SARS coronavirus outbreak had reduced lung function and quality of life, and more frequent viral respiratory illnesses. The latter are associated with increased risk for childhood wheeze and asthma, the most common chronic and disparate disease among children. Data also indicate that there are significant racial/ethnic disparities in COVID-19 outcomes. Disparities in risk of viral exposure, susceptibility to severe disease, and access to health care may interact to exacerbate existing health inequalities. Pregnancy provides a natural mechanism by which to examine the protective potential of passive immunity. Maternal IgG is actively transported across the placenta and in the absence of postnatal exposure wane to undetectable levels in the neonate over the first year of life. Furthermore, IgA is passed from mother to child through breastmilk. Our multidisciplinary team will study a unique cohort of Puerto Rican mothers and their infants prospectively following the infants through their first five years of life collecting maternal breastmilk, maternal and neonatal cord blood, and neonatal/infant nasal epithelium swabs at birth, during respiratory illness, and at yearly clinical evaluations. We will determine prenatal exposure to SARS-CoV-2 as measured from maternal and infant cord blood at time of birth and investigate the effect this virus has on the susceptibility of respiratory disease in children. We will screen all pre/postpartum mothers with a PCR assay and qualitative immunoassay to detect SARS-CoV-2 infection. Among all seropositive mothers, we will collect repeated breast milk samples at 5 and 14 days and serial newborn blood spot samples at birth, 1, 3, 6 months, and yearly for 5 years. We will measure IgA, IgG, and IgM in maternal breastmilk and blood samples, and IgG in infant serum. We will examine (Aim 1) the passive transfer of SARS-CoV-2 immunity from seropositive mothers to their neonates, (Aim 2) whether early life SARS- CoV-2 infection severity and other clinical sequelae is modified by altered childhood immunophenotypes and host genetics, and (Aim 3) how socio-environmental factors affect maternal and infant exposure to COVID-19 and further affect the development of childhood asthma. We hypothesize that pregnant women infected with SARS-CoV-2 produce neutralizing antibodies, which protect their newborns from COVID-19 disease. In contrast, infants who contract SARS-CoV-2 after birth are at increased risk for later respiratory disease including asthma and other clinical sequelae. We further postulate that these associations are modified by host genetic and socio- environmental factors. To our knowledge, there are no other groups within or outside the U.S. with the population needed and track record to perform these analyses.",2021,2022,N/A,646280,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2021 +C15265,1R01DK130454-01,Decode the Impact of SARS-CoV-2 on Human Pancreas,"Abstract. Recent clinical data has suggested a bidirectional interaction between Coronavirus disease 19 (COVID-19) and diabetes. Individuals with diabetes and severe obesity are more likely to be complications, and have a higher COVID-19 mortality rate symptomatic . Conversely, new-onset diabetes and severe , are at a higher risk for metabolic complications of pre-existing diabetes have been observed in COVID-19 patients. Thus, there is a strong need to understand the pathology and mechanism of pancreatic dysfunction in COVID-19 patients. Here, we demonstrate the detection of SARS-CoV-2 in pancreatic endocrine cells in autopsy samples from COVID-19 patients. Single cell RNA-seq and immunostaining confirmed that multiple types of pancreatic islet cells are susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS- CoV-2 infection, beta cells show a decreased expression of insulin and the increased expression of alpha and acinar cell markers, including glucagon and PRSS1/trypsin1, respectively, suggesting cellular transdifferentiation. Hyperion technology to examine the pathogenesis of autopsy samples of COVID-19 patients. In addition, we will use human islets and a vascularized human pancreatic organoid models to systematically evaluate the role of direct infection and paracrine inflammation signal on human endocrine cells cellular identities, function and survival. In the proposal, we will apply state-of-art Through this study, we would expect to provide a systematic overview of the pathological changes in the pancreas of COVID-19 patients, as well as a detailed mechanism to understand endocrine cell dysfunction, which will pave the road to the development of novel therapy to protect endocrine cell function in COVID-19 patients.",2021,2024,N/A,440068,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15266,3U42OD010918-22S1,Facilitation of Post-Acute Sequela to COVID Studies in Mouse Models,"PROJECT SUMMARY An overarching goal of the Mutant Mouse Resource and Research Center at the University of Missouri (MU- MMRRC) is to optimize and refine mouse models so that biomedical research using these models can proceed rapidly and effectively. The study of COVID-19 has relied on mouse models such as the B6.Cg-Tg(K18- ACE2)2Prlmn/J mouse (K18-hACE2). While great advances have already been made, some studies, notably those assessing Post-Acute Sequela of COVID-19 (PASC) are hampered by the fact that infected mice are currently maintained at animal biosafety level 3. These facilities often have limited capacity, resulting in delays in research and the elevated costs associated with this level of biocontainment. The study of disease pathogenesis associated with reinfection of SARS-CoV-2 and cross infection with variants is also hampered as such studies are by nature longer in duration and also require the need for PASC assessment. Thus, there is a pressing need to establish strategies by which studies of PASC can be accomplished more quickly and economically. Herein we propose that such studies can be performed in modified biosafety level 2 conditions, provided that viral clearance is established to a point acceptable to investigators as well as experts in institution biosafety and animal care and use. The objective of this proposal is to assess the kinetics / natural history of SARS-CoV-2 in the K18-hACE2 mouse model to determine when clearance is reliably observed and to establish standard operating procedures for the safe transfer of mice from ABSL-3 facilities to more accessible and less expensive ABSL-2 facilities. To broaden the applicability of these strategies to future research, studies will be performed using two different routes of infection and three different variants of the virus. Moreover, we will also perform these studies using two gut microbiomes that differ in species richness and that have been associated with differing disease susceptibility in preliminary studies. A second objective will be to similarly assess the kinetics of reinfection by SARS-CoV-2 and cross infection with two different variants of virus. The resulting expansion of the utility of models of COVID-19 for PASC studies will be critical to research on this devastating disease.",2021,2025,University of Missouri,466389,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2000 +C15267,7R01MH114847-04,Mining Social Media Messages for HIV Testing and Prevention Communication,"PROJECT SUMMARY The spread of the SARS-CoV-2 in the US has created novel problems with methods successfully underway in the parent grant that use cutting edge, Big Data techniques for processing vast and diverse data (text, videos, images) to select actionable and acceptable social media HIV messages that match the HIV biomedical needs of target US counties. These problems include: (a) the messages we are currently selecting are not relevant in the context of the pandemic and the current machine learning methods take many months to optimize; (b) combination SARS-CoV-2/HIV messages would be necessary but the methods to produce them have not been developed; and (c) no methods to multiply scarce or new messages have been validated. This emergency- supplement application requests the resources to offset these problems and to use the opportunity to generate new knowledge about HIV and responses to pandemics. Our new approach will use the same successfully tested techniques to select, generate, and deliver combination messages about HIV (i.e., testing, PrEP, and condom use) and messages about social distancing, testing, prevention, and treatment of the SARS-CoV-2, specifically for Men who have Sex with Men (MSM). The current pandemic also serves as a reminder that vaccination is lacking in MSM; therefore, the supplemental project will integrate messaging about vaccines, including an eventual one against SARS-CoV-2. To counteract the new problems resulting from insufficient numbers of appropriate HIV messages for the SARS-CoV-2 times and to adapt current methods which are too time-consuming and inflexible for messaging in such a changing environment, we need (1) new, rapid methods to identify actionable and acceptable messages; (2) new methods to combine HIV recommendations with emerging public health recommendations related to SARS-CoV-2; and (3) new methods to rapidly multiply the resulting messages for social media. Thus, this funding application will pursue the following: Aim 1. Extend current methods to identify regional needs related to the SARS-CoV-2 pandemic and vaccines, Aim 2. Deploy new rapid methods of message selection for a pandemic, and Aim 3. Experimentally test the effect of the new methods by sending (a) the selected experimental messages (combined with links to local service information) to managers of social media accounts and (b) a random selection of HIV/SARS-CoV-2 messages to a group of control counties. This significant and innovative project will be facilitated by unique team expertise in communication and persuasion, Big Data methods, public health, and Bayesian spatio-temporal modeling, and by the participation of leading institutions in the areas of psychology, public health, and computer science. The project is synergistic with new data collection efforts associated with the American Men Internet Survey, which will now collect SARS-CoV-2 seroprevalence data, which will be supplemented to conduct additional behavioral data for the project proposed in this application.",2021,2023,N/A,584635,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Communication,2018 +C15268,1R01DK130362-01,Endotheliopathy and liver injury in COVID-19,"COVID-19, caused by SARS-CoV-2 infection, is a multisystem disease. SARS-CoV-2 infection in airway cells and other tissues results in excessive production of proinflammatory cytokines, which can lead to pulmonary failure. The lung damage is caused in part by thrombotic complications from endotheliopathy, a form of endothelial dysfunction characterized by a proinflammatory and procoagulant state. This is a major cause of morbidity and mortality in patients with COVID-19. Clinical liver injury is often observed in COVID-19 and is associated with a worse prognosis than in patients without liver injury, but the pathophysiology remains unknown. The goal of our proposal is to determine the mechanism of liver injury in COVID-19. The presence of thrombosis was reported in the livers of COVID-19 patients. We found that liver injury (ALT greater than three times the upper limit of normal) is associated with an increase in procoagulant factors in the blood (n=3,830) and in liver tissue (n=48) from COVID-19 patients. Given that endotheliopathy activates the coagulation cascade and leads to platelet adhesion to the endothelium, which promotes thrombosis, we hypothesize that an excessive immune response to SARS-CoV-2 infection leads to endotheliopathy in the liver microcirculation, causing liver injury. IL-6 is a proinflammatory cytokine that is highly elevated in the blood of COVID-19 patients. We found that IL-6 levels were significantly higher in COVID-19 patients with liver injury than those without. IL-6 levels also positively correlated with plasma levels of von Willebrand factor (vWF), an indicator of endotheliopathy. IL-6 can initiate intracellular signaling both through a membrane-bound IL-6 receptor (IL-6R) (classical IL-6 signaling) as well as by binding to soluble IL-6R (sIL-6R). The latter is known as IL-6 trans-signaling and allows IL-6 signaling into cells not expressing IL-6R on the cell surface, such as liver sinusoidal endothelial cells (LSECs), as long as they express gp130. We thus hypothesize that IL-6 trans-signaling causes LSEC endotheliopathy (a proinflammatory and procoagulant state) and liver injury observed in COVID-19 patients, and that blocking this pathway will ameliorate endotheliopathy. Two aims are proposed. Aim 1 Determine the mechanism of LSEC endotheliopathy that leads to liver injury in COVID-19. Aim 2 Determine potential therapeutic targets for LSEC endotheliopathy in COVID-19. New therapies for COVID-19 will be needed for a long time to come. Here we will examine in a mechanistic manner a new therapeutic strategy for COVID-19 and its endotheliopathy. Because IL-6 signaling is largely unexplored in ECs, findings from this study will advance our understanding of not only the mechanism of thrombosis in the liver microcirculation, but also EC biology in general. Further, our model of IL- 6 driven liver injury is likely to be highly broadly relevant to SARS-CoV-2 endothelial injury and could also provide attractive therapeutic targets.",2021,2024,N/A,418750,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2021 +C15270,1R01HL157634-01,COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS),"The long-term health impact of COVID-19 remains uncertain. We are already providing post-hospitalization care for thousands of COVID-19 survivors at Columbia University Irving Medical Center (CUIMC) in New York City. This study is designed to help our and other medical centers care for COVID-19 survivors by using gold- standard imaging approaches to describe the major sequelae of severe COVID-19. The possibility of significant vascular and parenchymal sequelae of severe COVID-19 is suggested by the prominent Alverolar- arterial gradients observed clinically, plus histopathology confirming substantial endothelial and epithelial damage. Nonetheless, precise assessments of vascular and parenchymal sequelae in vivo have been limited, especially for the vasculature, and long-term follow-up to assess recovery or progression is lacking. Our investigative team has developed and refined a dual-energy computed tomography (CT) protocol to provide direct measures of the pulmonary vasculature, including pulmonary parenchymal perfused blood volume (PBV); and, detailed phenotyping of the parenchyma, including ground glass opacity (GGO) textures, which we have identified by an adaptive multiple features model (AMFM) approach in preliminary work among COVID-19 survivors. In multiethnic cohort studies, we have associated these CT measures with development and progression of chronic lung diseases. To strengthen our investigation into potential microvascular mechanisms of COVID-19 lung injury, this application will also test if PBV is associated with biomarkers of inflammation, hypercoagulability, and complement activation. We will randomly sample 200 adults without a prior diagnosis of chronic lung disease who were hospitalized for COVID-19 at CUIMC and did not require intubation, plus 100 seronegative controls matched on age, sex, race, ethnicity, body mass index, and neighborhood. All participants will undergo contrast-enhanced dual-energy CT, diffusing capacity of the lung for carbon monoxide, spirometry, questionnaires, and phlebotomy for SARS-CoV-2 antibodies and biomarkers. These measures will be performed 3-12 months and 27-36 months post-COVID hospital discharge to accomplish three specific aims. Aim 1 is to define lung microvascular sequelae of COVID-19. We hypothesize that PBV in COVID-19 survivors will be lower and more heterogeneous, and that these abnormalities will be associated with levels of IL-6, CRP, d-dimer, C5a, MBL, and MASP-2. Aim 2 is to define lung parenchymal sequelae of COVID-19. We hypothesize that there will be greater GGO texture patterns in COVID-19 survivors. Aim 3 is to explore if COVID-related differences in lung structure and procoagulant biomarkers are maintained up to 3 years after acute illness. We hypothesize that two years following the baseline study visit, parenchymal and biomarker abnormalities will normalize, but vascular abnormalities will progress. Accomplishment of the Aims will guide post-COVID care and risk stratification, suggest targets for therapeutic interventions, and inform policies for risk mitigation and public health in the COVID-19 era.",2021,2025,Columbia University Irving Medical Center (CUIMC) in New York City,734821,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +C15271,3R01AI134384-05S1,No more business as usual: responding to the COVID-19 pandemic through open data genome and evolutionary analytics.,"The rapid worldwide spread and severe regional outbreaks of COVID-19 following its emergence in Wuhan in November 2019 has created a sense of urgency and alarm. There are many more cases (>100,000) and deaths (~5,000) than in other recent viral outbreaks/epidemics (SARS, MERS, Ebola and Zika viruses); but in many other respects the epidemic is ""typical"" - zoonotic introduction from a (yet undetermined) animal reservoir, followed by a period of undetected transmission among humans (with possible adaptation to the new host), and then generalized transmission. The same types of questions arise during each of these emerging outbreaks: Where did the pathogen come from? Is it evolving in the human population? How is it spreading? How to develop reliable diagnostics? What are promising vaccine targets? Many, if not all, of these questions depend on rapid and reliable genomic analysis of diverse viral sample sequences by multiple laboratories. Yet, time and time again, including COVID-19, we encounter the same avoidable shortcomings early in the viral investigation: lack of reproducibility, rigor, and data/analytic sharing. The initial publications describing genomic features of COVID-19 [1-4] used Illumina and Oxford nanopore data to elucidate the sequence composition of patient specimens (although only Wu et al. [3] explicitly provided the accession numbers for their raw short read sequencing data). However, their approaches to processing, assembly, and analysis of raw data differed widely and ranged from transparent [3] to entirely opaque [4]. Such lack of analytical transparency sets a dangerous precedent. Infectious disease outbreaks often occur in locations where infrastructure necessary for data analysis may be inaccessible or unbiased interpretation of results may be politically untenable. Essential questions such as the extent of intra-host genomic variability (indicative of adaptation or multiple infection), viral evolution (selection, recombination), transmission (phylogentic and phylogeographic) cannot be answered reliably if researchers cannot trust/replicate the source data and analytical approaches. The key goals/deliverables of this supplement will be the open analytic workflows that can be used to curate and standardize genomic data, and high quality annotated variation data for SARS-CoV-2 and potential future outbreaks. These workflows will be distributed through proven, fully open, and highly used infrastructure provided by the Galaxy (http://covid19.galaxyproject.org) and HyPhy/Datamonkey (http://covid19.datamonkey.org/) projects.",2021,2022,N/A,368281,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,,,2020 +C15272,1R01DK130351-01,Impact of SARS CoV2 on post-hospital recovery of carbohydrate and muscle metabolism: role of endothelial injury,"Project Summary/Abstract This proposal tests the novel hypothesis that pre-existing diabetes (or new stress hyperglycemia), exacerbates the systemic impact of COVID-19-mediated microvascular injury and slows recovery via persistence of hyperglycemia and diabetes related persistent endothelial injury. Our long-term goal is to understand the post-infection consequences of COVID-19 infection on carbohydrate metabolism and diabetes complications. Decreased effective perfusion of the islets and skeletal muscle may contribute to the post- infection sequelae of COVID-19 infection such as decreased insulin secretion and insulin action and fatigue. The goal of this proposal is to examine the short-term impact of COVID-19 infection on post- hospitalization carbohydrate and skeletal muscle metabolism, and to test the correlation of hyperglycemia and diffuse endothelial injury with these late endpoints. Hypothesis: COVID-19 deleteriously impacts carbohydrate metabolism and skeletal muscle function due to systemic perfusion abnormalities, worse in diabetes; post-hospitalization recovery of these parameters will be slowed in the context of hyperglycemia and endothelial injury. SA#1: Test the hypothesis that COVID-19 impairs insulin secretion and action and that post- hospitalization recovery is slowed in the context of persistent hyperglycemia and/or diffuse endothelial injury. The relative contribution of decreased insulin secretion versus systemic insulin resistance to COVID-19 mediated hyperglycemia is unknown, as are the factors contributing to dysglycemia. Studies under this aim will evaluate the relationship of diffuse endothelial injury and dysglycemia to carbohydrate metabolism in people with and without diabetes post-hospitalization using an oral glucose tolerance test. SA# 2: Test the hypothesis that dysglycemia and diffuse endothelial injury slow skeletal muscle recovery post COVID-19. No data exist on post COVID-19 functional status recovery or skeletal muscle function comparing people with and without diabetes. These experiments will examine post-hospitalization muscle oxidative flux, insulin action and perfusion and explore the correlation of these parameters, glucose profiles and endothelial injury in people with and without diabetes post COVID-19 hospitalization. Impact: Successful execution of the proposed studies will provide new information on recovery from COVID- 19 with regards to carbohydrate metabolism and frailty. These data may inform post-hospitalization glycemic management to lessen the long-term consequences of COVID-19 in people with diabetes.",2021,2024,N/A,398573,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other | Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15273,1R21ES033119-01,CRST COVID-19 - Wayakta He,"Title: CRST COVID-19 Wayakta He? (Are you on guard against COVID?) PI: E. Erdei Project Summary Ongoing concurrent pandemics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections and toxic exposures originated from electronic cigarette (e-cig) and secondhand smoke had taken devastating tolls on minority communities in the U.S. Rather than being ""the great equalizer"" due to universal lack of immunity, evidence has shown that the burden of COVID-19 disease has been disproportionately felt by racial/ethnic minority and low-income communities. This stark and most current health disparity is likely due to a variety of psychosocial stressors stemming from structural inequalities that place individuals of color and/or low socioeconomic status, including American Indian/Alaska Native communities at greater risk for the contraction of SARS-CoV-2 infection and severity of COVID-19 disease. A recent literature showed that overall COVID-19 diagnosis was associated with youth use of e-cigarettes. However, that study did not look specifically at younger generation of American Indian and Alaskan Native (AI/AN), and how other factors within tribal communities affect disease susceptibility. This proposal is submitted in response to ""Mechanism for Time-Sensitive Research Opportunities in Environmental Health Sciences "", RFA-ES-19-011. Aim 1 will employ a community-based data collection of socioeconomic and environmental stressors in the Cheyenne River Sioux Tribal (CRST) communities in South Dakota by administering a tribal-specific survey, which will constitute the CRST SARS-CoV-2 infection prevalence collected in 300 participating CRST households with 600 distinct participants representing a wide-range of ages (18-89 yrs). The development of novel and time - sensitive data during the ongoing CRSRT pandemic on social factors and environmental toxicants will expand under Aim 2 by capturing detailed personal behaviors (i.e. vaping), stressors, Tribal housing, and by measuring environmental health factors that may impact COVID-19 disease susceptibility, severity and immune response. Detailed immunological assessment (total IgA, viral-specific IgG & IgM positivities and cortisol) will be carried out by using non-invasive saliva sampling. These measures will help us to assess the association between risk factors from Aim 1 survey data and RT-PCR confirmed SARS-CoV-2 viral infection prevalence. Based on passive air monitoring we will be able to evaluate the association between airborne exposures to nitrogen dioxide and airborne nicotine in the homes with increased susceptibility for SARS-CoV-2 infections and increased viral-specific IgM and decreased protective IgG response. We will assist CRST COVID-19 Command Center by generating a community-driven, COVID-19 targeted, public health literacy, and by capturing population-based infection susceptibility risks and specific immune response data. Our hypothesis is that increased SARS-CoV-2 infections among CRST community members are associated with vaping and indoor secondhand smoke, lower socioeconomic status, the type of heating sources used in homes, large multigenerational households (>3.4 people in one home), and living in multi-unit Tribal housing complexes.",2021,2023,N/A,217464,Human Populations,Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +C15274,1R01AI164481-01A1,Enriching SARS-CoV-2 sequence data in public repositories with information extracted from full text articles,"Project Summary In response to the COVID-19 pandemic, scientists have published over one hundred thousand research articles and made available over eight hundred thousand virus genome sequences. These sequences, along with their metadata, can be used to understand virus evolution and spread and their implications for public health, a field of study called genomic epidemiology. However, these sequence records do not typically contain patient metadata such as demographics, clinical severity, or comorbidities, preventing researchers from uncovering trends in population health. To understand the severity of the problem, we analyzed nearly 748 thousand SARS-CoV-2 records from GISAID and 60 thousand from GenBank for the presence of patient metadata finding age and gender were represented in < 1% of GenBank records and in GISAID, 26% included sex, and 24% had age. For other fields, the amount of missing data is even more pronounced, with neither resource providing information on a patient's race and only GISAID specifying severity (i.e. ICU) in less than 5% of records. To address missing virus metadata, researchers could utilize the publication associated with the new sequences, however, the virus sequence record is often never updated with a link to the publication. From the set of records that we analyzed, 3.4% (of 748K) in GISAID and < 1% (of 117K) in GenBank had a link to a publication. This greatly hinders secondary data analysis of these sequences and limits the ability to use them at scale to uncover associations between the viral genome, transmission risk, and health outcomes. The goal of this proposal is to enhance genomic epidemiology and population health of COVID-19 with a framework to continuously and automatically enrich SARS-CoV-2 nucleic acid sequence metadata in public databases such as GenBank and GISAID with metadata in associated published articles. We will incorporate input from clinicians at the front-line of patient care during the pandemic and build on our NIH funded work (R01AI117011), which used Natural Language Processing (NLP) to enrich the geographic metadata of a sequence record using its corresponding published article. We have used these data in virus phylogeographic models and shown the benefit of using enriched metadata for modeling virus evolution and spread. Theavailability of SARS-CoV-2 sequences, paired withfull- text COVID-19 articles and preprints, presents an opportunity for metadata enrichment and scientific discovery beyond our prior work. Our specific aims are to: (1) enrich SARS-CoV-2 sequence metadata using text extracted from publications and (2) derive key epidemiologic insights for different patient demographics using our enriched SARS-CoV-2 sequence dataset. We will leverage our prior joint work funded by the NIH to enable the secondary use of enriched metadata for genomic epidemiology to improve our understanding of SARS-CoV-2 evolution and spread among different population groups. We will disseminate the enriched data through our GeoBoost2 data dashboard, GenBank LinkOut and the i2b2 platform. The latter will more immediately allow integration with COVID-specific clinical data shared by the 4CE Consortium.",2021,2024,N/A,757140,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +C15275,1R01AI163029-01,Inborn errors of immunity in patients with life-threatening COVID-19,"Project Summary There is immense interindividual clinical variability in humans infected with SARS-CoV-2, ranging from silent infection to lethal COVID-19. The first breakthrough to crack this enigma came from the field of inborn errors of immunity (IEI). In an international cohort of 659 patients, we reported 23 patients with IEIs at eight influenza susceptibility loci that govern TLR3- and IRF7-dependent type I interferon (IFN) immunity (3.5%), including four unrelated patients with autosomal recessive IRF7 or IFNAR1 deficiency. We also reported an additional 101 patients with neutralizing autoantibodies (auto-Abs) against type I IFN (10.2% of 987), who were auto-immune phenocopies of the patients with IEI. Interestingly, 94% of the patients with auto-Ab against type I IFN were men, and one of the six sick women had X-linked dominant incontinentia pigmenti (IP), suggesting X-linked inheritance in at least some of the patients. Collectively, these patients account for about 13.5% of life-threatening COVID- 19 cases studied. We now hypothesize that other IEI that result in abnormal (i) production or amplification of type I IFN, (ii) activity of soluble type I IFNs (via neutralizing auto-Abs), or (iii) response to type I IFN (in terms of interferon stimulated gene (ISG) activity), can underlie life-threatening COVID-19 in other patients. To tackle these three specific aims, we benefit from an international recruitment from the COVID Human Genetic Effort (https://www.covidhge.com). Our preliminary data are very strong. First, we have found 215 patients with predicted loss-of-function (pLOF) variants at 157 loci associated with production or amplification of type I IFN, including one patient homozygous for a pLOF variants in NLRC3, two patients heterozygous for pLOF variants in DDX58/RIG-I, and six patients heterozygous for pLOF variants in subtypes of type I or III IFNs. Second, among patients with auto-Ab against type I IFN, we identified a patient hemizygous for a pLOF in X-linked SASH3. In addition, we found that 25% of patients with IP, which is associated with severely skewed X-inactivation, have auto-Ab against type I IFN, further suggesting an X-linked basis of auto-Ab to type I IFN production. Third, we found 24 patients with pLOF variants in 18 ISGs. We have shown that the international path-breaking program we established in only 6 months is highly efficient, as it resulted in a paradigm-shifting discovery. Our new program will benefit from this momentum. Our future discoveries of new inborn errors of type I IFN immunity underlying life-threatening COVID-19 pneumonia will pave the way for new diagnostic and therapeutic strategies to better manage patients infected with SARS-CoV-2 at risk of severe disease. Selected patients may benefit from subcutaneous or nebulized IFN-a or IFN-b (defect in type I IFN production or amplification), plasmapheresis and/or B cell depletion (neutralizing auto-Abs against type I IFNs), or other therapies, including mAbs against SARS-CoV-2 (defects of ISGs).",2021,2026,N/A,762750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15276,1R56AI158314-01,Role and Mitigation of Inflammasomes and Inflammation During COVID-19,"Abstract The COVID-19 pandemic caused by SARS-CoV-2 has resulted in swift and catastrophic losses of human lives globally. Acute respiratory distress syndrome (ARDS) is one of the most detrimental outcomes of COVID-19 infection that can lead to the rapid deterioration and death of patients. ARDS is primarily caused by the cytokine storm which unleashes a plethora of inflammatory cytokines during the late stages of COVID-19. The master cytokines that are thought to be responsible for much of the damage are interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor (TNF). Currently several clinical trials have already been initiated to test the efficacy of biologic inhibitors to target these pathways. However, in many cases, the mechanism and impact of these cytokines during ARDS are poorly understood. An indepth mechanistic understanding of cytokine induction is important because this understanding will significantly impact the design and success of ARDS treatment. This application focuses on the role and mitigation of the inflammasome complex which leads to the proinflammatory cytokine, IL-1β, in ARDS. The inflammasome is a protein supramolecular structure that leads to caspase 1 activation, which then cleaves pro-IL-1β and pro-IL-18 to mature IL-1β and IL-18. In addition to the release of IL-1β and IL-18, caspase 1 cleaves gasdermin D to cause inflammatory pyroptotic cell death, thus leading to a cascade of cell death and inflammation. The inflammasome is comprised of a receptor or sensor, with the most prominent ones represented by NLRP1, NLRP3, NLRP6, NLRC4 and AIM2. It also includes an adaptor molecule ASC (apoptosis- associated speck-like protein containing a CARD), and the effector caspase-1. Each receptor or sensor can be activated by specific pathogen products called PAMPs or cell damage associated molecules called DAMPs. NLRP3 is the most studied member since it is activated by a large list of stimulators. Studies of other coronavirus such as SARS show inflammasome activation by key viral proteins. Expression data from COVID-19 patients also show dramatic increases of inflammasome sensors in the bronchial alveolar lavage of COVID-19 patients. However the mechanism of inflammasome activation by SARS-CoV-2, especially in the human system, remains unknown. This proposal will identify the viral protein that activates human inflammasome, and further define the specific human inflammasome sensor/receptor that mediates the response. We will then design ways to reduce inflammasome activation during SARS-CoV-2 infection using established therapeutics as well as new approaches to broadly attenuate inflammatory cytokines.",2021,2022,N/A,768215,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15277,1R01AA029859-01,Microbiota-Mediated Bidirectional Interactions Between Alcohol Misuse and Post-COVID-19 Syndrome,"PROJECT SUMMARY Recent data show that 10-30% of coronavirus disease 2019 (COVID-19) patients do not fully recover and suffer from a wide range of symptoms that persist after the SARS-CoV-2 infection has been cleared (so-called post- COVID-19 syndrome or Long Hauler). Severe COVID-19 and associated risk factors appear to increase the risk of developing post-COVID-19 syndrome and yet a substantial number of patients without known risk factors also develop post-COVID-19 syndrome. Thus, additional risk factors leading to post-COVID-19 syndrome must exist. One potential risk factor is excessive alcohol consumption. (1) Alcohol is the most frequently used drug in the United States, and alcohol use increases during public health crises, especially in socioeconomic disadvantaged communities. (2) Alcohol results in inappropriate immune responses to pathogens. (3) Alcohol disrupts intestinal and lung barrier integrity which can further promote inflammation. We recently showed that increased serum Zonulin (a marker of disrupted intestinal barrier integrity) and increased endotoxin (LBP) are associated with inflammation during COVID-19 and can predict disease severity and mortality. Accordingly, we hypothesize that: (a) there is a bidirectional interaction between alcohol misuse and SARS-CoV-2 infection leading to increased risk of post-COVID-19 syndrome in patients with alcohol use disorder (AUD) and more severe AUD in COVID-19 patients; and (b) the underlying mechanism of these interactions is microbiota dysbiosis and/or disruption of intestinal barrier integrity, promoting inflammation and dysregulated immune-responses to the virus. To test our hypotheses, we will leverage our NIAAA supported COVID-19 supplement at Rush University Medical Center (RUMC), which is actively following more than 7,000 SARS-CoV-2 positive patients and 2,000 SARS- CoV-2 negative patients over 12 months using structured questionnaires. All patients are screened for alcohol use/misuse. Furthermore, we will recruit a subset of patients to provide biological samples to test our mechanistic hypothesis evaluating the link between AUD, post-COVID-19 syndrome, and gut-derived inflammation. In Aim 1, we will test the hypothesis that AUD increases the risk and severity of post-COVID-19 syndrome by promoting gut-derived inflammation. (1a) We will determine if increased alcohol use/misuse is associated with risk and severity of post-COVID-19 syndrome. (1b) We will elucidate the role of gut-derived inflammation in AUD promotion of the post-COVID-19 syndrome by interrogating stool microbiota composition/function, systemic markers of intestinal barrier integrity, inflammation, and immune activation. In Aim 2, we will test the hypothesis that COVID-19 increases the risk and severity of AUD and alcohol-induced intestinal barrier disruption. (2a) we will determine whether post-COVID-19 syndrome is associated with increased risk of AUD. (2b) We will determine if COVID-19 decreases resilience of intestinal barrier to the damaging effects of alcohol which would result in increased risk of alcohol-induced intestinal leak that could lead to organ damage using organoids generated from individuals with and without post-COVID-19 and/or AUD.",2021,2024,N/A,215870,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts,2021 +C15278,3R25GM129809-03S1,Drug Discovery and Biomedical Research Training (DDBRT) Program for Underserved Minority Youth,"Project Summary/Abstract The Drug Discovery and Biomedical Research Training (DDBRT) Program at the University of Maryland Eastern Shore School of Pharmacy (UMES SOP) mentors, trains, and motivates minority high school students in Somerset County to pursue education and careers in the applied healthcare fields and biomedical research. Somerset County is one of the most rural and underserved communities in the State of Maryland, with one of the highest COVID-19 positivity rates and lowest COVID-19 vaccinations out of any Maryland district, especially among minority populations. The proposed project will use a multi-component approach leveraging strengths of the DDBRT to disseminate information and reduce vaccine hesitancy in under-vaccinated populations through in-person workshops, volunteering at a COVID-19 vaccination site, digital media campaigns, video production, and social media platforms. An expert panel of healthcare providers, public health workers, teachers, and religious leaders will implement a curriculum compromised of interactive modules about scientific findings on SARS-CoV-2 and SARS-CoV-2 vaccines, recognizing misinformation, and overcoming SARS-CoV-2 vaccine hesitancy aimed at high school students, teachers, and their families. This will be presented in-person and recorded on websites, social media, and YouTube for the community. High school students will help to design two student-hosted videos featuring different topics to improve vaccine confidence that will be placed on websites, YouTube, and on social media. Participants will also apply these principles learned at a COVID-19 vaccination event to address remaining vaccine-related misconceptions. The high school students and SEPA PIs will use the UMES Facebook page to disseminate COVID-19 and vaccination scientific findings to the community on a weekly basis. The program is expected to occur from July 2021 to June 2022. This proposal is innovative by combining the expertise of pharmacists, the main providers of SARS-COV-2 vaccines with specific knowledge of issues related to vaccine hesitancy, with influential community leaders to educate and empower students from a medically underserved population. These students will become COVID-19 vaccine champions and serve as ambassadors to encourage their teachers, family, and community to get vaccinated through novel educational resources. Overall, the expected outcome aligns with the parent DDBRT program by stimulating the student's interest in and pursuit of pharmaceutical, health-related, and biomedical research careers by actively connecting in-classroom biomedical studies with the real-world pandemic that is disproportionately affecting their community.",2021,2024,University of Maryland Eastern Shore School of Pharmacy,54000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15279,1R01DK130481-01,Mechanistic Studies of Gut Dysfunction Exacerbation due to SARS-CoV-2 in HIV/SIV infected Individuals,"Abstract With more than 60 million SARS-CoV-2 -infected patients worldwide and nearly 1.5 million COVID-19-related deaths recoreded thus far (November 25), the COVID pandemic is one of the most critical global health problem ever known to humankind, and a major emergency in the US. COVID-19 disproportionately impacts elders or subjects with pre-existing conditions. Considering that the majority of persons living with HIV and AIDS (PLWHA) in the US are aged over 50 years and that even the younger PLWHA present with accelerated aging and multiple comorbidities related to HIV-induced excessive chronic inflammation, it is expected that COVID-19 will be particularly severe in this risk group. Similar to HIV, SARS-CoV-2 replicates in the gut, and patients with gastrointestinal symptoms were reported to have a more severe outcome. The exact mechanism through which SARS-CoV-2 impacts the gut health remains elusive, however it is very likely that the two viruses can potentiate each other through exacerbation of the gut lesions. Here, we will test the hypothesis that exacerbation of the gut dysfunction of the SIV-infected PTMs after SARS-CoV-2 superinfection occurs through triggering excessive mobilization, activation and NETosis of neutrophils at mucosal site and consequent gut collateral damages. Such a scenario will result not only in an increased risk of the PLWHA to develop more severe forms of COVID-19, but also to a significant boost of HIV pathogenicity through (i) losing control of HIV at mucosal sites; (ii) depletion of mucosal and systemic immune effectors; (iii) increases of mucosal and systemic levels of inflammation; and (iv) enhancement of pre-existent SIV-related comorbidities. This innovative project is designed to assess pathogenic pathways impacted by SARS-CoV-2 in the gut, to understand the natural history of COVID-19 related to either triggering or exacerbating HIV-associated gut dysfunction and comorbidities. We will identify risk factors that could prompt therapy changes in high-risk individuals, such as the PLWH. Our highly translational project addresses key scientific questions identified as critical by the NIDDK, thus being highly responsive to RFA 20-021.",2021,2024,N/A,391250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15280,1R01AI163216-01,Developing three-dimensional antisense oligonucleotide drugs against COVID-19,"Project Summary (Abstract) Developing three-dimensional antisense oligonucleotide drugs against COVID-19 The culprit of coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has a very large RNA genome that encodes the proteins and RNA elements required for all aspects of viral infection and replication. This property makes the virus vulnerable to a new class of drugs called antisense oligonucleotide (ASO). ASOs are single-stranded synthetic nucleic acids that achieve therapeutic effects by binding to viral or other target RNAs via Watson-Crick base pairing, the very interaction that defines molecular biology and the foundation of life. The first ASO drug approved by the U.S. Food and Drug Administration is an antiviral against cytomegalovirus. A major challenge of developing ASO antiviral drugs is the strong tendency of RNA to fold into structures that interfere with ASO hybridization. Current ASO design methods do not adequately address this problem. We have developed a structure-based ASO design technology platform that takes advantage of three- dimensional structures of target RNAs. Our ""3D-ASOs"" recognize not only the sequences but also the shapes of SARS-CoV-2 RNAs. Compared to conventional designs, 3D-ASOs contact viral RNAs more extensively and therefore can achieve greater affinity and specificity. Our technology platform includes four design templates and a 3D-ASO drug development workflow that employs an innovative RNA structure determination method. In a preliminary study, we designed and tested several 3D-ASOs against SARS-CoV-2 viral RNA and identified two lead sequences that strongly inhibit viral replication in cultured human cells to a much greater extent than previously reported sequences. In the proposed research, we will optimize the lead 3D-ASOs by altering their backbone modifications and bases for tighter binding and better fit to the viral RNAs and for stronger inhibition to their functions. We will also cast our net wide by designing and testing additional anti-SARS-CoV-2 3D-ASOs. Finally, the most potent 3D-ASOs will be tested in an animal model. If successful, the project will provide ASO drug candidates for clinical trials. These drugs may be given as nasal sprays or via intravenous injection, as treatments or for prevention. The structure-based design technology we will refine is generally applicable to ASO drug development. Therefore, this research has the potential to turn tide on the battlefield against COVID-19 and in our fight with many other diseases.",2021,2026,N/A,426633,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15281,1R01MD016738-01,The ADELANTE Trial: Testing a multi-level approach for improving household food insecurity and glycemic control among Latinos with diabetes,"PROJECT SUMMARY Latinos account for the largest share of SARS-CoV-2 (COVID-19) cases (60%) and deaths (48%) compared to any other racial/ethnic group in California. Additionally, Latino households have experienced a dramatic increase in household food insecurity due to the pandemic. This is especially distressing for Latinos with type 2 diabetes (T2DM) as household food insecurity is associated with worse glycemic control, which has life- threatening consequences during the COVID-19 pandemic. T2DM, and especially poorly controlled T2DM, is a risk factor for death from COVID-19. Effective multilevel interventions to improve household food insecurity and glycemic control are urgently needed for Latinos with diabetes to mitigate disparities due to COVID-19. The goal of ADELANTE (Addressing Diabetes by ELevating Access to Nutrition: A Trial of Effectiveness) is to determine whether a multi-level intervention to improve household food insecurity and glycemic control is effective for Latino patients with diabetes. We will use a type 1 hybrid trial to assess the effectiveness of the multilevel intervention on the primary outcome of glycemic control (HbA1c) at 6 months. Participants (n=355) will be randomized to either: 1) 12 weeks of household deliveries of fiber-rich foods (vegetables, beans/legumes, and whole grains) plus a 12-month remotely delivered, culturally-adapted lifestyle behavioral intervention called Vida Sana, or 2) a waitlist control arm, receiving the intervention after a 6-month delay. We will follow participants for 12 months to assess the primary outcome ofHbA1c at 6 months as well as key secondary outcomes such as HbA1c at 12 months, and diabetes- and COVID-related stress at 6 and 12 months. Additionally, we will recruit up to 2 household members for each participant to assess household-level secondary outcomes such as household food insecurity, dietary behaviors, and COVID-related stress. To assess the future potential of implementation and dissemination of the multilevel intervention in primary care we will use mixed methods including quantitative measures (e.g., intervention dose and fidelity) and qualitative interviews with participants and key stakeholders (e.g., providers, clinic leadership, community supported agricultural group) according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. We will involve patients and our longstanding community partners in all phases of the trial. The trial will take place in Alameda County, California, which is home to a large and diverse Latino population, at La Clínica de La Raza, a community safety net clinic with multiple locations throughout Alameda County. Successful completion of these aims will provide robust evidence of the effectiveness of improving household food insecurity and glycemic control among Latinos with diabetes during the pandemic.",2021,2026,N/A,669976,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Research on Capacity Strengthening","Disease pathogenesis | Supportive care, processes of care and management | Indirect health impacts | Individual level capacity strengthening",2021 +C15282,1R21AI161104-01,VPS34 inhibitors as SARS-CoV-2 antivirals,"Summary SARS-CoV-2, a Betacoronavirus genus, is an enveloped positive-sense, RNA virus responsible for a current pandemic. Because of its profound impact on society and human health there is an urgent need to understand SARS-CoV-2 replication requirements and to identify therapeutic strategies. Repurposing drugs developed for other purposes may provide a shortcut to therapeutic development. The use of compounds known to target specific host factors may also elucidate key pathways needed for virus replication. Coronavirus (CoV) replication involves multiple critical interactions with host cell membranes. One of the most striking features of CoV infection is the establishment of membrane-associated replication organelles that serve as the main sites of viral RNA synthesis. The origin of these membrane organelles is incompletely understood. Because the specific host pathways required for SARS-CoV-2 replication organelle formation are not defined, we asked whether SARS-CoV-2 is susceptible to modulators of lipid metabolism by assessing the sensitivity of the virus to VPS34 inhibitors of VPS34, a lipid kinase required for autophagy and endosomal trafficking; Triacsin C, an inhibitor of long chain fatty acyl CoA synthetase (ACSL) and Orlistat, an inhibitor of fatty acid synthase (FASN). Our preliminary data indicate that inhibitors of VPS34 potently inhibited SARS-CoV-2 replication, whereas an FDA- approved inhibitor of a different class of PI3K had minimal effect on replication. Targeting FASN and ACSL also impairs SARS-CoV-2 replication. These data suggest that VPS34, ACSL and FASN play important roles in replication center formation and virus growth and suggest these enzymes as therapeutic targets. We will test the hypothesis that VPS34, ACSL and FASN are critical for SARS-Cov-2 infection by evaluating additional small molecule inhibitors of these enzymes and by measuring SARS-CoV-2 replication in genetic knockdowns or knockouts of these host enzymes. We will define mechanisms of inhibition and test the hypothesis that generation of membrane-associated viral replication centers will be disrupted. Finally, we will assess the in vivo efficacy of VSP34 inhibitor PIK-III and systemically administered Orlistat in SARS-coV-2- infected hamsters to evaluate the therapeutic potential of inhibitors of lipid metabolism.",2021,2023,N/A,429000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15283,1R21EB032025-01,Development and Evaluation of Radiotracers for PET Imaging Angiotensin-Converting Enzyme 2 (ACE2),"PROJECT SUMMARY The coronavirus disease2019 (COVID-19) pandemic is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). New COVID-19 cases and COVID-19 related deaths continue to rise rapidly and no effective drugs or vaccines are currently available. The functional entry receptor utilized by SARS-CoV-2 is Angiotensin-Converting Enzyme 2 (ACE2). SARS-CoV-2 binds to ACE2 in the lower respiratory tracts of infected patients to gain entry into lung cells, leading to viral pneumonia and potentially fatal respiratory failure. Many studies have shown that patients with comorbid conditions including respiratory disease, cardiovascular disease, kidney disease, diabetes, and hypertension have much higher mortality rates. ACE inhibitors and angiotensin receptor blockers (ARB) are frequently used to treat these pre-existing conditions and the question remains whether such treatment may affect the outcome in COVID-19 patients due to the inhibitors' effects on ACE2 expression. Many experts are concerned that those inhibitors for the treatment of patients with such underlying conditions may exacerbate COVID-19 symptoms and lead to higher mortality rates. Currently the precise relationship between ACE2 levels and severity of the infection is not well understood, due to a lack of understanding of whole-body ACE2 expression levels and distribution. Here we propose to design and synthesize a series of new fluorine-18 labeled positron emission tomography (PET) tracers targeting ACE2. The radiotracers will be evaluated in vitro for cellular binding affinity, selectivity, and metabolic stability. The most promising radiotracer will be moved to in vivo studies including whole body biodistribution with dynamic PET imaging, and correlation with biomolecular analysis in mice that express human ACE2. The PET imaging modality will provide a powerful tool for noninvasive and quantitative evaluation of ACE2 levels in living subjects. Furthermore, the radiotracer may help to unveil the precise relationship between ACE2 levels and severity of COVID-19.",2021,2024,N/A,213000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15284,1R21AI164769-01,How the Novel Coronavirus Attacks the Brain,"Presentations of patients infected with SARS-CoV-2 are varied and unique in their neurological manifestations, including loss of smell, confusion, and altered mental status, when the course of the novel coronavirus disease (COVID-19) is complicated by insults to the neurological system. The nasopharynx and nasal cavities are reservoirs for high viral load and olfactory tissue contains key receptors and proteases that may facilitate viral entry and replication at the cellular level. Downstream mechanisms of brain cellular invasion and integration remain poorly understood, particularly how SARS-CoV-2 may be instigating diffuse neurological effects. Patients with COVID-19 sustain a severe cytokine storm, the interplay between inflammation and coagulation combined with endothelial damage, may lead to thrombo-embolic events, and microglia activation leading to neuronal damage. Patients also present with long-term brain sequela of COVID-19, including ""brain fog,"" difficulties concentrating, impaired short-term and working memory, fatigue, headache, dysautonomia, and insomnia, and the neuropathological bases of these symptoms are unknown. Appropriate evaluation of specific brain regions from deceased patients with COVID-19 who did and did not present with neurological symptoms will allow for improved comprehension of possible targets to limit brain damage. Additionally, lessons from how SARS-CoV-2 affects the brain may provide insight into generalizable mechanisms for effects of neuroinflammation on neurodegenerative diseases. We aim to determine: 1. Whether COVID-19 patients with neurological presentations at the time of intake (NP-COVs) have altered brain expression of genes regulating inflammation and coagulation compared to those without (COVs) and non-COVID-19 age and sex matched controls (CONT). We will map the whole transcriptome in the entire brain tissue section using single nuclei RNA sequencing (sn-RNA-seq, 10X Genomics). We will validate and quantify candidate mRNAs expression on neurons, glia, and vasculature-associated cells, using Duplex RNAscope® (ACDBio), as we successfully performed in CONT. 2. Whether NP-COVs have elevated brain pro-inflammatory markers. We will run a Human Cytokine/Chemokine/Growth Factor Panel (48 Plex Kit, Milliopre) and quantify cytokines, chemokines and growth factors. We will map their expression on neurons and glia, using double immunohistochemistry (IHC), as we piloted in CONT. 3. If NP-COVs have elevated brain microglia activation. Using double-IHC for microglia markers TSPO (translocator protein), CD11b, Iba1 (Ionized calcium binding adaptor molecule), and neuronal markers, and stereology for cell quantification, we will compute activated (amoeboid) and resting (small cell body and elaborated thin processes) microglia, and map spatial relationship to neurons. 4. If NP-COVs have reduced neuronal density and dendrite arborization. Using double-IHC for neuronal marker NeuN and neurofilament, Stereoinvestigator and Neurolucida (MBF Inc.), will quantify neuron density, dendrite length and arborization, as in our pilot studies.",2021,2023,N/A,328391,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15285,1R21AI158176-01,Develop Potent Methyltransferase Inhibitors to Target Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2),"The recently emerged coronavirus disease-2019 (COVID-19) that commenced in Wuhan China has spread globally at an unprecedented speed. The etiological pathogen for this pandemic disease is a new, enveloped, positive-sense, single-stranded RNA coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). The genome of SARS-CoV-2 is evolutionarily related to the betacoronavirus that caused the SARS outbreak in 2003. Currently there are no targeted effective therapeutics and no vaccines for the viral prevention. In order to rapidly innovate effective medications for clinical curing of this viral infection, we are launching a drug discovery campaign with combined team efforts to develop new therapeutic agents against COVID-19. We aim to target the nonstructural protein 16 (nsp16) of SARS-CoV-2, the ribose 2′-O-methyltransferase enzyme (2′-O- MTase) that is responsible for the formation of viral RNA cap-1 structure, the last step of the 5'-capping of the coronavirus. The methylation mechanism is important for both viral replication and viral evasion by host immune recognition. Thus, drugs targeting the 5'-capping pathway are ideal for eliminating the virulence of this pathogen. The X-ray crystal structures of nsp16/nsp10 protein complex of SARS-CoV-2 have recently been resolved, which showed a great structural similarity to the SARS-CoV nsp16/nsp10 complex structures. The availability of these high-resolution structures provide the important structural basis for screening and design of nsp16 inhibitors. In this project, we will combine computer-aided in silico screening, sensitive biochemical assays, and antiviral cell assays to identify potent nsp16 inhibitors to combat this coronavirus. We will carry out structure-based high- throughput virtual screening to rapidly discover effective inhibitors of the nsp16 2'-O-MTase. The top screening hits will be subjected to biochemical screening against recombinant nsp16 enzyme of SARS-COV-2. Validated nsp16 2'-O-MTase inhibitors will be tested for antiviral activity against SARS-CoV2 strains. The accomplishment of this drug discovery campaign is to generate a novel avenue of experimental therapy against the existential COVID-19 pandemic via inhibiting the 5'-capping pathway of the coronavirus.",2021,2023,N/A,415250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15286,3P30NR016587-05S2,Reaching Communities through the Design of Information Visualizations (ReDIVis) Toolbox to Address COVID-19 Vaccine Hesitancy and Uptake.,"The alarming disproportionate impact of the COVID-19 pandemic on underserved as well as medically and socially vulnerable populations requires generating new knowledge to help mitigate its effects. We will address existing knowledge gaps in two specific aspects of COVID-19 mitigation strategies - return of SARS-CoV-2 test results and COVID-19 vaccination - through synergistic application of community-engaged research and novel informatics approaches in collaboration with our community partners: the Association to Benefit Children, Project New Yorker, and the Chinese American Planning Council. In addition, for this Supplement, which builds upon our RADx-UP Phase 1 project, Reaching Communities through the Design of Information Visualizations for Returning COVID-19 Results (ReDIVis Toolbox: RCR), we have formed a strategic partnership with the New York City Community Engagement Research Alliance (NYCEAL) Against COVID-19 Disparities to leverage the evidence-informed communication resources of CEAL. The overall goal of Reaching Communities through the Design of Information Visualizations Toolbox (ReDIVis Toolbox: Vaccination) is to decrease health disparities related to COVID-19 vaccination in underserved and vulnerable populations by enabling widespread use of culturally congruent and health literate infographics to decrease vaccine hesitancy and improve vaccine uptake in a manner that is comprehensible, informs decision making, and motivates appropriate behaviors. Our specific aims build upon: (a) our accomplishments to date in our RADx-UP Phase 1 project; (b) the rich resources of the Visualization Design Studio of the Precision in Symptom Self-Management (PriSSM) Center, the qualifying grant for this emergency competitive revision in response to NOT-OD-21-101; and (c) partnership with NYCEAL through a subcontract with New York University. We will use a mixed-methods design to achieve the following specific aims: (1) Advance understanding of the factors that influence comprehension and use of the results of SARS-CoV-2 diagnostic and antibody testing, and COVID-19 vaccine hesitancy and uptake in underserved and vulnerable populations; (2) Collaborate with underserved and vulnerable populations to design infographics for returning the results of SARS-CoV-2 diagnostic and antibody testing, and for addressing vaccine hesitancy and uptake in a format that maximizes comprehension, informs decision making, and motivates action; and (3) Develop, implement, evaluate, and disseminate the ReDIVis Toolbox to create infographics for returning the results of SARS-CoV-2 diagnostic and antibody testing and addressing vaccine hesitancy and uptake. ReDIVis Toolbox: Vaccination directly responds to multiple areas of interest including strategies to communicate culturally and linguistically appropriate information about COVID- 19 vaccines to foster vaccine confidence and acceptance, and dissemination and communication strategies to amplify or extend the reach of the voices of local community leaders/stakeholders and health professionals to promote COVID-19 prevention tools.",2021,2022,N/A,284499,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15287,3R25GM142096-01S1,Encouraging Excellence: Health Science Education in Native American Communities,"The University of Nebraska Medical Center will continue to leverage the trust and cooperative spirit that we have garnered working with tribal schools and communities in Nebraska and South Dakota to develop, implement, and evaluate science curriculum, outreach activities, and training experiences targeting Native American students in grades K-12 and their teachers. The long-term goals of this project are to promote student interest in the sciences, foster a more science-literate public, and ultimately increase the number of Native Americans entering health and science careers. Advancing the health of Native American communities is the ultimate aim of every aspect of this project. Improved science teaching and heightened awareness of health careers will encourage students to enter these careers and hopefully bring these skills back to their communities. Public outreach that increases health literacy and healthy living will promote better personal health decisions. This supplement request seeks to expand our SEPA program to include the development of novel online modules that introduce students to concepts in virology and immunology with a specific focus on SARS-CoV-2 and vaccine development and hesitancy as has been observed in different populations during this pandemic. Vaccine hesitancy is not limited to this era of the coronavirus pandemic. Thus, an increase in general knowledge will be beneficial as the world returns to normal and as the prospect of future outbreaks begins to recede in people's memories.",2021,2026,The University of Nebraska Medical Center,53999,Human Populations,Other,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Minority communities unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Social impacts,2021 +C15288,1R01MH127856-01,Sex specific immune response to SARS-CoV-2 leads to chronic neurologic symptoms,"PROJECT SUMMARY To date over 16 million people in the US have been infected with the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). While the vast majority will survive the acute illness, many are at risk for experiencing long-term symptoms after the acute illness. Acute neurologic symptoms including encephalitis, strokes and seizures have been reported in COVID- 19 patients. Increasingly, even survivors without acute neurologic conditions have reported neuropsychiatric symptoms (NPS) months after their illness. The incidence and factors that influence the development of long- term NPS is unknown. SARS-CoV-2 infection triggers a systemic pro-inflammatory response termed `cytokine storm', characterized by an uncontrolled release of pro-inflammatory molecules. The consequences of uncontrolled systemic inflammation on the brain and the link to long-term NPS after COVID-19 is unknown. Sex differences in the outcome from COVID-19 are increasingly evident. Men have worse outcomes with acute COVID-19 infection, with higher hospitalization rates and mortality, an effect seen globally. Sex differences in the immune literature acute inflammatory circulating immune responses underlie the differences i n the acute disease course, as seen both in t he and in our preliminary data. We have found that men have a more robust innate immune response to COVID-19 infection, with increased circulating neutrophils and monocytes and higher serum levels of cytokines and markers of brain injury (neuron specific enolase). In contrast, women have more T and B cells in response to acute infection compared to men, hallmarks of an antigen-specific response.Interestingly, our preliminary data suggest that women however, may be disproportionally affected by the chronic effects of infection, including higher rates of NPS. To examine the mechanism of NPS, we propose a longitudinal, prospective study to assess the impact of acute and chronic inflammation on markers of brain injury, and long-term NPS for up to 2 years after COVID-19 infection. To accomplish this, we will leverage our prospective clinical biorepository and long-term COVID-19 follow-up clinic. To date, over 400 hospitalized COVID-19 patients from three different hospitals have been enrolled into a prospective biorepository and Houston is now at the verge of another surge. Identifying patients at risk for developing chronic consequences of COVID-19 infection, and discovering potential underlying mechanisms leading to NPS will be critical to the enhance the health of millions of COVID-19 survivors.",2021,2026,N/A,766078,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2021 +C15290,3U19AG063720-02S2,The Study of Women's Health Across the Nation (SWAN): The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age,"The Study of Women's Health Across the Nation (SWAN): The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age. Administrative Supplement ABSTRACT The Coronavirus Disease 2019 (COVID-19) pandemic, has dramatically changed the way we live and interact. In addition to claiming more than 220,000 lives and infecting more than 8 million people in the United States (US) to date, many more millions have suffered economically through job or business loss; suffered from social isolation, anxiety or depression; and have not received or delayed medical care. This administrative supplement to SWAN-Aging: The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age (1U19AG063720-01A1) is in response to the Notice of Special Interest NOT-AG-20-022: NIA Availability of Administrative Supplements and Revision Supplements on COVID-19. The pandemic is especially pertinent to SWAN-Aging participants as they are a high-risk, and potentially high-exposure, population given their age and residential locations. The Study of Women's Health Across the Nation (SWAN) is a multi-racial/ethnic cohort of women, enrolled at age 42-52 and followed for over 25 years with longitudinal measures of economic strain and stress, health behaviors, cognitive and physical functioning, and mental and physical health. SWAN-Aging will prospectively link comprehensive longitudinal characterization of the menopause transition (MT) and midlife health indicators to functioning and multiple health domains in early old age (65-75 years), including cognitive impairment and cognitive decline, physical functioning, psychological well-being, sleep, and cardiovascular and bone health. A follow-up visit, planned to start July 2021, provides a unique opportunity to evaluate the longer-term impact of the pandemic on women's economic security, access to health care, their cognitive and physical functioning, and physical and mental health in early old age. SWAN- Aging's overall goal is to enhance understanding of successful aging in women. Without collecting time- sensitive data on COVID-19 infection and its consequences, SWAN-Aging will not be able to account for the impact of the pandemic on participants' health and well-being. This administrative supplement is designed to evaluate the effect of infection and symptoms, social and economic disruption, and delayed medical care on multiple aspects of health and functioning in early old age. The wealth of previously collected longitudinal data will allow us to a) account for person-specific, pre-pandemic trajectories of biology, functioning, and health, when disentangling the causal impact of the COVID-19 pandemic from aging, and b) delineate risk and protective factors for pandemic-related effects on health and functioning. Its goals are 1) to characterize COVID-19 infection (seropositivity, symptoms, and hospitalizations) and determine longer-term effects of the pandemic on health and functioning in SWAN-Aging women; 2) to determine the effect of the pandemic and mitigation efforts on economic security, social engagement, health behaviors, and health and functioning outcomes; and 3) to determine the effect of COVID-19-related delays in receiving medical care on health.",2021,2024,N/A,196732,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences | Approaches to public health interventions | Indirect health impacts | Social impacts,2020 +C15291,1R01AI161278-01,"Structure, function, and inhibition of the SARS-CoV-2 replication-transcription complex","Project Summary COVID-19, caused by the coronavirus SARS-CoV-2, continues to devastate the world. In less than a year, there have been more than 20 million cases with over 700,000 deaths. The viral RNA-dependent RNA polymerase (RdRp) is the central enzyme responsible for transcription and replication of the viral RNA genome. This enzyme is also a target for the current antiviral, remdesivir, used to ameliorate the severity and duration of this disease. The virus also encodes several nucleic acid processing enzymes, in addition to the RdRp, including a helicase, an endonuclease, an exonuclease, and methyltransferases. However, it is unknown how these enzymes coordinate to transcribe and replicate the viral genome. This proposal builds upon preliminary data of the structure of the helicase, nsp13, in complex with the RdRp and a primed substrate RNA (nsp13-replication/transcription complex or nsp13-RTC). The aims here include completing the structural analysis of this complex by utilizing additional data collected. The result of this aim will provide higher resolution (better than 2.7 Å in some parts the RdRp), providing a rich basis for the development of antiviral inhibitors. Also, having this structure in hand allows for the collaboration with expert developers of antimicrobials, also part of the aims, including the investigation of the structural details of the pre-incorporation state of remdesivir and antivirals produced by human microbiome. The models resulting from the structure of nsp13-RTC serve as foundations to test how the helicase and exonuclease function together with the RdRp. Specifically, real-time fluorescence assays, single-molecule fluorescence resonance energy transfer (FRET), and multi-color fluorescence microscopy will be used to probe the role of the helicase and the exonuclease in unwinding substrate RNA, backtracking, and proofreading. Another aim applies the pipeline used to characterize the nsp13-RTC assembly, which yielded a high- resolution structure of the complex, to other RTC assemblies. Specifically, native electrophoretic mobility assays will be used as a starting point to probe larger assemblies of the RTC. Native mass-spectrometry will then be used to determine the composition and stoichiometry of the complexes. Finally, cryo-EM will be applied to solve the structures of these macromolecular machines. The resulting structures will provide a starting point to elucidate the coordinated functions of these enzymes, provide insight into their mechanisms, and establish novel targets for therapeutics. In summary, this proposal aims to understand at the molecular and structural level how the SARS-CoV-2 nucleic acid processing enzymes coordinate to replicate and transcribe the viral genome, and to provide structure-guided targets for drug discovery, with the ultimate goal of providing relief for the COVID-19 pandemic.",2021,2026,N/A,638072,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history",2021 +C15292,3P50DA048756-03S3,Optimizing SARS-CoV-2 Testing and Promotores Interventions to Serve Latinx Communities,"PROJECT SUMMARY The global SARS-CoV-2 pandemic is the worst health crisis the United States and world have faced in a century. Although this highly contagious virus has infected tens of millions of Americans already, the pandemic is far from over, and the disease burdens continue to be disproportionately born by historically underserved populations such as Latinx communities. Nationally, Latinx people with COVID-19 are hospitalized at four times the rate of Whites and have much higher rates of morbidity and mortality. This disparity is notable in Oregon, where the 13% of our population that is Latinx represents approximately 24% of COVID-19 cases. Yet, vaccination rates for Latinx remain below the state average. Thus, an urgent need exists to reach Oregon's Latinx community with public health and prevention messages that emphasize the value of continued COVID-19 testing and that address vaccine hesitancy. This project will build upon our successful RADx-UP Phase I culturally-tailored community outreach and testing program through the implementation of Phase II goals of increasing the reach and uptake of testing and decreasing vaccine hesitancy in Latinx individuals in Oregon. The project will maintain and expand a world-class team of prevention scientists, public health experts, Latinx researchers, community partners, and biologists who have been working together to conduct SARS-CoV-2 diagnostic testing since March 2020. This team established a CLIA-certified laboratory and honed molecular testing protocols, procured millions of dollars of diagnostic testing equipment and supplies, and partnered with county public health offices and hospitals throughout the state to conduct testing. The team has been engaged in comprehensive community partnerships using community-based participatory research methods in Phase I to deliver a culturally-tailored intervention that shows preliminary efficacy in increasing testing among Latinx individuals. Building on the lessons learned in the first 6 months of our Phase I RADX-UP testing, we will refocus our existing testing program to broaden our reach by partnering with state and community organizations offering other services to Latinx communities across Oregon. With continued support from the Latinx Community and Scientific Advisory Board, the project will refocus to support the testing of 100 individuals each month across the state of Oregon, focusing specifically on locating testing events at venues that serve Latinx individuals (e.g., mobile Mexican Consulate events across the state). The previously launched health intervention (Promotores de Salud) will also be refocused to promote the benefits of continued testing and vaccination uptake, and barriers to these important health behaviors will be evaluated. Over time, this project will continue to help communities institutionalize optimal local testing frameworks that are sustainable. The resulting testing and structures and systems will be poised for future scale-up to other vulnerable communities and/or for other public health purposes. This project is expected to lead to a major reduction in COVID-19 health disparities in underserved populations.",2021,2023,N/A,1104555,Human Populations,Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15293,3U54GM115516-05S2,Understanding Factors Influencing COVID-19 Testing and Vaccination in Immigrant Low-income and Homeless Populations and Testing Targeted Interventions,"The COVID-19 pandemic has disproportionately affected people from vulnerable and disadvantaged communities. Research to date has highlighted the factors that contribute to these disparities including differential treatment and experience of marginalized populations in healthcare and research settings, reduced access to testing and care, living in congregate or multigenerational households, the economic consequences of being diagnosed with COVID-19 and quarantining, differing understanding of and attitudes towards the pandemic, and concerns about contact tracing. Immigrant and low income populations, and people experiencing homelessness, many with mental illnesses, and/or have been recently incarcerated, are hesitant to participate in testing and to accept COVID-19 testing and vaccination. There is an urgent need to understand how to deliver information about testing and vaccination that is understandable and resonates with higher risk communities in their cultural and social contexts. Effective public health strategies for delivering this information must include community input and partnerships. Working closely with community partners who have insight into cultural, behavioral, economic, and factors impacting people's decision making about testing and vaccine acceptance is essential to developing effective communication and outreach strategies for engaging individuals in testing, vaccination, and care. Working with our community partners, we will create and evaluate the impact of a public health intervention in the area of Cumberland County, Maine, to provide outreach, testing, and vaccination education to a large community of immigrants from sub-Saharan Africa, the Middle East, and Central America, higher-risk low-income people accessing a public health facility (with a sexually transmitted infections clinic, needle exchange, and a free clinic), and individuals experiencing homelessness. This will be a longitudinal study to understand beliefs about and knowledge of COVID-19, and barriers and beliefs about testing and vaccination. Results will inform a community-developed and based intervention to engage the cohort and other members of these populations in testing and vaccine education, and evaluate the impact of this intervention on testing and vaccination uptake in our immigrant, low-income, and homeless communities. Specific Aims: 1) To understand patient perceptions of, fears about, and experiences with COVID-19 testing and vaccination, including booster vaccination in our immigrant, low- income, and homeless populations. 2) To use the data from Aim 1 to develop and pilot test a public health messaging and testing program to increase vaccine and testing uptake in our populations of interest. 3) To evaluate the impact of a public health messaging and testing program developed in Aim 2 on rapid COVID-19 testing and vaccine uptake. While it will need to be adapted based on local communities' cultures and needs, this work could be foundational for creating and sustaining public health measures that will contribute to the control of the pandemic and reducing the COVID-19 related disparities of vulnerable populations in the US.",2021,2022,N/A,940910,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Indigenous People | Sexual and gender minorities | Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15294,1R01AA029831-01,Characterize multifaceted interactions between COVID-19 and alcohol use disorder based on real-time analysis of electronic health records of 62 million adult patients,"PROJECT SUMMARY During the pandemic, with social isolation and grief as drivers, alcohol consumption is increasing. SARS-CoV-2 itself has substantial impact on the central nervous system. When two such important public health menaces intersect, it is crucial to understand their interaction and potential synergy. In this project titled ""Characterize multifaceted interactions between COVID-19 and alcohol use disorder based on real-time analysis of electronic health records of 62 million adult patients"", we propose to: 1) characterize susceptibility to COVID-19 in patients with alcohol use disorder (AUD) (""AUD → COVID-19""), consider racial and gender disparity, and follow its evolution over time; 2) characterize how COVID-19 infection and the social pandemic context impact the risk of AUD (""COVID-19 plus pandemic context → AUD""), consider racial and gender disparity, and follow these changes over time; and 3) characterize prevalence of major psychiatric disorders, other substance use disorders and severe outcomes among patients with both AUD and COVID-19 (""AUD+COVID-19 → outcomes"") and to follow these outcomes over time. Our studies will identify potential areas for timely interventions to protect patients or mitigate the worst effects of COVID-19 pandemic and AUD, singly and combined. This is especially important if there should be another surge with a virus variant, or if vaccine hesitancy is greater in those with AUD. It will also inform such studies if we have another pandemic with another organism, for the approaches we pioneer in these studies using nation-wide database of electronic health records may pave the way for rapid, real-time analytics and results to inform our control measures.",2021,2024,N/A,362250,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts,2021 +C15295,1R21AI166840-01,Broad-based spike protein stalk-based vaccine platform for SARS-CoV-2 and other coronaviruses,"Project Summary/Abstract We propose to develop a subunit vaccine for SARS-CoV-2, using a structure-based approach targeting conserved and functionally essential domains in the stalk region of the viral spike protein. We expect our vaccine platform to be applicable and effective across a wide range of existing and emerging coronaviruses. As our system is based on expression in E. coli is it expected to be cost-effective, and our stalk-based approach is specifically designed to cover a range of distinct coronaviruses. However, it is important to note that our vaccine platform is highly flexible, with the antigen able to be re-engineered rapidly in the face of a novel coronavirus that may emerge, and for which the vaccine developed in this application is not effective.",2021,2023,N/A,196250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C15296,1R01DK130425-01,Experimental and natural SARS-CoV-2 infection of the human pancreas,"ABSTRACT The possibility that infection with SARS-CoV-2 may trigger diabetes emerged as a concern in mid 2020. We have addressed this issue by developing a research roadmap that identified complementary areas of investigation according to several broad topics in the realm of relevant basic biomedical research. Based on our recent publication about the expression of SARS-CoV-2 entry factors in the non-diabetic human pancreas, we have now developed a Research Strategy that will assess the principal capacity of pancreatic SARS-CoV-2 infection and its primary consequences in a series of in vitro, in vivo and ex vivo studies distributed across three Specific Aims: In Aim 1 we will define expression patterns of ACE2 and other viral entry factors in dispersed human pancreatic cell populations; will subject islets to in vitro SARS-CoV-2 infection and quantify infection patterns as well as alterations of single-cell proteomes and transcriptomes by flow cytometry, high-dimensional mass cytometry, and scRNAseq; will determine functional islet responses under conditions of viral infection by dynamic glucose-stimulated insulin secretion; will conduct mechanistic studies with targeted ACE2 blockade and by generation of ACE2-deficient beta-like cells; and will explore SARS-CoV-2 infection in the context of living pancreas slices that provide a more ""physiological"" experimental platform for in vitro studies. In Aim 2, we will use the robust ""minimal mass"" model of human islet transplantation into immunodeficient mice to delineate metabolic perturbations (blood glucose values, plasma insulin, intraperitoneal glucose tolerance test) accrued in the wake of an in vivo SARS-CoV-2 challenge. To address the considerable experimental and logistical challenges in these studies, we have developed a tiered approach that progressively refines experimental designs (including use of a recently generated, sequenced and characterized mouse-adapted [ma] SARS-CoV-2 strain) with the goal to imbue our models with escalating biological relevance. In Aim 3, we will draw on our access to COVID-19 and control autopsy cases to reveal the ex vivo viral burden of natural SARS-CoV-2 infection in the pancreas. These studies, which build on recently published pilot data as well as extensive preparatory studies to adjust our staining protocols to the demands of at times suboptimal tissue quality, will define SARS-CoV-2 protein and mRNA abundance, cellular association and distribution patterns across the COVID-19 pancreas. We will further leverage an established immunohistochemical multiplexing strategy to define the identity, quantity and distribution of major immune cell subsets throughout COVID-19 and control pancreata. Thus, the proposed work will generate an inclusive perspective on the cardinal viral and immunological components of the potentially altered pancreatic histology in COVID-19. Collectively, the proposed work addresses, and is expected to resolve at least in part, key aspects of the hypothesis that SARS-CoV-2 infection may precipitate diabetes onset. Together with emerging epidemiological data, it may therefore provide an important foundation for future risk assessment and the prioritization of prophylactic and/or therapeutic intervention strategies.",2021,2024,N/A,453320,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15297,3R01HD093680-04S1,COVID-19 Vaccine and Menstrual Health in Adolescents,"Project Summary/Abstract Menstrual characteristics can provide critical information about women's overall health and well-being. Yet, recent clinical trials for the COVID-19 vaccine failed to gather this information. This is particularly relevant, as anecdotal reports have suggested that the COVID-19 vaccine may be affecting menstrual patterns and characteristics. Additionally, potential mechanisms underlying this relationship, such as inflammatory responses or stress, have not been identified. The overarching objective of this administrative supplement, ""COVID19 Vaccination and Menstruation,"" is to evaluate the relationship between administration of the COVID- 19 vaccine and menstrual health (i.e., cycle length, duration of bleeding, spotting between periods, menstrual flow, and menstrual pain) in a sample of 80 healthy adolescent girls (ages 14-18 years; estimated n=64 who will receive the vaccine, and n=16 who will not receive the vaccine and serve as the control group) with varying levels of menstrual pain who are not using any exogenous hormones. This objective will be achieved through the following specific aims: 1) characterize the relationship between the COVID-19 vaccine and inflammation, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress); 2) identify the impact of inflammatory markers on measures of menstrual health, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress); and 3) determine if the COVID-19 vaccine is associated with changes in menstrual health via changes in inflammation, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress). As part of the parent study, participants provide baseline levels of menstrual health data and are assessed monthly to characterize menstrual health (cycle length, menstrual pain, duration of menstruation, flow, and spotting between periods). Participation in this supplement will include obtaining measures of stress and saliva to assess for ovarian hormones, pro-inflammatory cytokines, and SARS-CoV-2 antibodies at 10 different time points (pre-vaccine, 24h post-vaccine, 48h post-vaccine, 14 days post-vaccine, and 28 days post-vaccine; repeated after 2nd dose of either Moderna or Pfizer-BioNTech vaccines, or repeated without a second dose if receiving the Johnson & Johnson vaccine). The control group will provide data on the identical timeline. These results are expected to determine whether a relationship between the COVID-19 vaccine and changes in menstrual health exist, and if so, elucidate possible inflammatory mechanisms underlying this relationship. Findings from the study will help characterize potential side effects of the COVID-19, thus reducing health disparities among reproductive-age girls and women.",2021,2024,N/A,299744,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Women,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Phase 1 clinical trial | Adverse events associated with immunization,2019 +C15298,1R01DK130378-01,Mechanisms for post-COVID pituitary damage,"PROJECT SUMMARY COVID-19-related extra-pulmonary damage is common and may even be observed in patients with mild COVID- 19 symptoms. There is an urgent and immediate need to establish optimal post-infection health care strategies for these patients, yet mechanisms underlying their appearance remain unexamined. For example, post-COVID- 19 chronic fatigue syndrome has been reported in 54% of COVID-19 survivors, including those without severe symptoms during the acute infection; however, its cause has not been addressed. Post-COVID-19 chronic fatigue syndrome's symptoms mimic those experienced by patients with well-described pituitary hormone deficiencies, supporting the concept that pituitary dysfunction in patients with COVID-19 may be implicated in post-COVID-19 health complications. Several lines of evidence support the premise that SARS-CoV-2 infection damages the pituitary, leading to disrupted pituitary function. First, we detected expression of the SARS-CoV-2 receptor ACE2 in the normal human pituitary by immunofluorescence, suggesting that SARS-CoV-2 may directly damage pituitary endocrine cells. Second, it has been reported that the SARS pandemic in Southeast Asia in 2002, by SARS-CoV-1, caused post-infection pituitary function decline, although direct damage to the pituitary was not investigated. Third, clinical observations suggest that patients with COVID-19 show aberrant immune activity and may develop cytokine storm, with particularly acute elevations of IL-6 and TNFα. Cytokine storm, which can occur as a consequence of with cancer immunotherapy treatment, for example, is frequently associated with pituitary inflammation and dysfunction, although the detailed pathogenetic mechanisms are not known. This suggests that aberrant activation of the immune system may also indirectly damage the pituitary in patients with COVID-19. Elucidating the mechanisms underlying direct and indirect pituitary damage related to SARS-CoV-2 infection is critical to establishing guidelines for timely diagnosis and management of pituitary dysfunction in COVID-19 survivors. In Aim 1, we will determine whether SARS-CoV-2 directly invades the pituitary and causes pituitary structural damage. We will study autopsy-derived pituitary tissues obtained from COVID-19 deceased patients and normal control pituitary tissues. Moreover, using a novel spatial genomics technology, we will determine changes in gene expression associated with COVID-19 in each of the five pituitary endocrine lineages and stroma cells. In Aim 2, we will determine the association and the timeline of pituitary dysfunction and symptoms in patients who were infected by SARS-CoV-2. By combining detailed and innovative cellular and molecular analyses, and clinical studies, we will identify the mechanisms responsible for pituitary dysfunction in COVID-19 patients and determine the course of pituitary dysfunction in COVID-19. These innovative studies will, in turn, enable the development of an evidence-based clinical guide for evaluation and management of hormone deficiencies in the vast COVID-19 population across the globe.",2021,2024,N/A,421625,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15299,3R01MH126531-01S1,"Structural and Social Determinants of Maternal Mental Health, Morbidity, and Inequities in COMBO","ABSTRACT The COVID-19 pandemic has highlighted and exacerbated health disparities related to structural racism and discrimination (SRD), economic marginalization, and other social determinants of health (SDOH). Pregnant and postpartum women face unique social and health vulnerabilities related to the pandemic, including risk for stigma, housing, food, income and employment insecurity, psychological distress, and even mortality - risks and consequences which are disproportionately significant and adverse for women of color and low socioeconomic status (SES). However, the collision of these multiple intersecting 21st century public health crises have not yet been empirically or rigorously studied for inequities in maternal mental health and severe morbidity. The COVID-19 Mother Baby Outcome (COMBO) initiative is a large multidisciplinary collaborative established at Columbia University Irving Medical Center to follow SARS-CoV-2 exposed laboring mothers and their newborns and compare their long-term health and wellbeing to case-matched dyads without prenatal exposure. The focus of the parent NIMH 'COMBO' R01 MH126531 is to understand the effects of SARS-CoV- 2 on mother-infant brain-behavior functioning in a subset of 100 COMBO-enrolled dyads with and without prenatal SARS-COV-2 infections. Responding to key priorities of NOSI NOT-OD-21-071 and leveraging COMBO's robust infrastructure, this administrative supplement (PA-20-272) expands the parent R01 to study the independent and interactive effects of SRD/SDOH and SARS-CoV-2 on inequities in maternal mental health, taking advantage of COMBO's unique setting (first pandemic epicenter) and understudied socially disadvantaged sample (>600 mother-infant dyads enrolled to-date, with 63% mothers identifying as racial/ethnic minority and/or low-SES women). By expanding parent R01 brain imaging, surveys, semi- structured interviews, and electronic health record (EHR) extraction, we will test the overarching hypothesis that SRD/SDOH and SARS-CoV-2 independently and additively increase risk of adverse maternal mental health outcomes, with the magnitude of the negative impact being greatest for women of social disadvantage and the health disparity gap ballooning during - and persisting post - the pandemic. Findings will inform patient-centered, multi-level interventions to ameliorate the intersecting epidemics of SRD/SDOH and SARS- CoV-2 and their mental health sequelae for women of social disadvantage in NYC and beyond.",2021,2026,Columbia University Irving Medical Center,881466,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Health Systems Research","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts | Social impacts | Health service delivery",2021 +C15300,5P20GM103648-09,Validation of a naturally-occurring animal model for SARS-CoV-2 infection,"The overall objective of this project is to validate mechanisms of viral fitness and immunopathogenesis during SARS-CoV-2 infection in domestic cats to establish baselines for downstream translational studies. Major goals (specific aims) for this project are as follows: Aim 1. Evaluate in vivo infection kinetics and viral fitness of SARS-CoV-2 in the domestic cat. We will use droplet digital PCR (ddPCR) to quantify absolute copy numbers of SARS-CoV-2 RNA in blood, nasal swabs, and respiratory tissues in order to characterize viral replication kinetics during acute infection in domestic cats, and compare these changes with co-expression of viral antigen and ACE2 receptors in respiratory tissues (IHC). We will also use virus amplicon sequencing assembly to evaluate the potential for genetic divergence in the feline host (i.e. does the virus evolve during infection in domestic cats). Hypotheses: SARS-CoV-2 infects ACE2-expressing feline respiratory cells, resulting in progressive replication of genetically conserved virus elements and lesions analogous to human COVID-19 Aim 2. Identify key factors of immune dysfunction contributing to COVID-19 disease progression. We will use scRNASeq, flow cytometry, and multiplex immunoassays to define shifts in the immune profile during acute SARS-CoV-2 infection. We will compare changes in immunological parameters with viral replication kinetics (Aim 1) and clinical disease progression in order to (i) define how perturbations of immune function impact clinical disease progression and (ii) identify novel immunomodulatory targets to guide more effective therapies or vaccine candidates. Hypothesis: Progression of severe COVID-19 in cats is analogous to human disease and correlated with (i) CD4+ and CD8+ T cell deficiencies and (ii) pro-inflammatory cytokine expression (IL-6, IL-1β, TNFα,)",2021,2023,N/A,240655,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease models | Animal source and routes of transmission",2021 +C15301,1R21ES033937-01,Impact of COVID-19 on disinfectant exposure and associated health effects.,"PROJECT SUMMARY/ABSTRACT Disinfectants are widely used in various products and in various settings to prevent infection and transmission of harmful pathogens. Disinfectants, however, contain hazardous chemicals and are known to cause irritation or allergic symptoms in eyes, skin, respiratory and nervous systems, asthma, and damage to organs with prolonged or repeated exposure. Quaternary ammonium compounds (QACs) are the most common active ingredients used in disinfectants approved for SARS-CoV-2 control. The coronavirus disease 2019 (COVID-19) pandemic led to dramatically increased use of disinfectants in the community and workplaces to prevent SARS-CoV-2 infection and transmission. Such increased use of disinfectants raises substantial concerns regarding the health effects of disinfectants. As for health risk by disinfectants, cleaning workers, particularly in healthcare settings, have been identified as occupational groups most affected by disinfectants. During the COVID-19 pandemic, with the heightened need for infection control in healthcare settings as well as increased use of disinfectants at home/community, these workers may have further increased health risks from disinfectant exposure. The purpose of this study is to assess the impact of the COVID-19 pandemic on disinfectant use and the incidence of disinfectant-related illness and examine the association between disinfectant exposure and health symptoms. We propose a study using three approaches: (1) Analysis of California Pesticide Illness Surveillance Program data (2011-2020) to investigate disinfectant-related illness cases in California. (2) A survey of 300 cleaning staff (predominantly Chinese and Hispanic) in a university health system in Northern California on disinfectant use and chemical-related health symptoms. (3) Measurement of two common QACs (benzalkonium chloride [BAC] and didecyl dimethyl ammonium chloride [DDAC]) in feces and urine in a subset of survey participants (n=100). The study has the following specific aims: (1) Characterize disinfectant-related illness cases in California during 2011-2020 and examine the trend of the annual incidence over time. (2) Characterize disinfectant use during COVID-19 among hospital cleaning staff and examine the relationship of disinfectant use with self-reported health symptoms. (3) Measure QACs (BAC/DDAC) in feces and urine among hospital cleaning staff and examine their associations with self- reported disinfectant use and health symptoms. This study will produce helpful information to assess the public health burden by the widely used disinfectants and the impact of COVID-19 on disinfectant exposure and health problems among the general population as well as the high-risk group of hospital cleaning staff. This study will be one of the first studies that measures and quantifies QACs in human samples to examine health effects. The biological data on QAC exposure among hospital cleaning staff will capture the body burden of disinfectant chemicals from both occupational and non-occupational exposures that increased during the COVID-19 pandemic, and will serve as a valuable foundation for analyses of longer-term health effects.",2021,2023,N/A,242250,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Infection prevention and control | Secondary impacts of disease, response & control measures","Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings | Indirect health impacts",2021 +C15302,3R01HD086742-05S2,An internet-based preconception cohort study in North America and Denmark,"ABSTRACT The proposed supplement responds to ""COVID19 Vaccination and Menstruation"" (NOT-HD-21-035). Clinical trials did not evaluate the influence SARS-CoV-2 vaccine on menstruation and anecdotal reports of menstrual changes after SARS-CoV-2 vaccination have circulated widely on social media, raising concerns about vaccine safety among the public. Pregnancy Study Online (PRESTO) is an NIH-funded prospective cohort study that enrolls women trying to conceive and follows them from preconception through 6 months after delivery (R01HD086742). Eligible female participants are aged 21-45 years, residents of North America, trying to conceive, and not using contraception or fertility treatment. During 6/2013-6/2021, PRESTO has enrolled more than 15,500 female participants. All questionnaires are completed online and data collection continued during the COVID-19 pandemic. In April 2020, we added new questions on COVID-19 infection and stressors related to the pandemic, including changes in lifestyle, behaviors and health care, and in January 2021, we added questions on SARS-CoV-2 vaccination (ever vaccinated, type of vaccine, and date of each shot). Since the study's inception, women have reported baseline data about their typical menstrual characteristics while not using hormones. After enrollment, women are offered a premium membership to Kindara.com, a menstrual charting app, in which they report day-specific menstrual data in real-time. On each bimonthly questionnaire (administered for up to 12 months), women report additional data about their most recent menstrual cycles. We will use the above prospectively-collected data to examine the extent to which SARS-CoV-2 vaccination is associated with changes in menstruation during 6 cycles of follow-up. Specifically, we will evaluate the association between SARS-CoV-2 vaccination and cycle irregularity, cycle length, intensity of bleed, duration of bleed, intermenstrual spotting/bleeding, and pain associated with menses. We will consider various windows of possible effects and identify the duration of any observed changes. We will control for several confounders, including COVID-19-related stressors. Among 1,800 U.S. participants who completed ≥1 follow-up questionnaire after 12/14/2020, we will compare menstrual characteristics between vaccinated and unvaccinated groups; we will also perform a self-matched analysis among 800 vaccinated women (pre- vs. post-vaccination). In the subset of ≥400 women who reported day-specific menstrual data using Kindara, we will characterize vaccine-related changes in menstruation. Our interdisciplinary research team has published extensively on vaccine-related health effects and menstrual characteristics, many of which are based on PRESTO data, and we have the expertise necessary to study these research questions. Given our ongoing prospective data collection throughout the pandemic, our successful recruitment of a large, diverse population of women not using hormones, and our prospective collection of menstrual data, PRESTO is uniquely-positioned to analyze data on vaccination and menstruation and provide essential information to the scientific community and the public on vaccine safety.",2021,2022,N/A,299328,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas | Europe,,,,,United States of America | Denmark,"Vaccines research, development and implementation",Adverse events associated with immunization,2016 +C15303,1R21EB031354-01,"Developing a Rapid, Simple-to-use Sensory Platform for Detection of Ultralow Concentration of SARS-CoV-2 Viral Particles Enabled by Electrophoretic Enhancement and Redox Cycling","Abstract: COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains an extraordinary global health crisis in the modern history. Meeting the testing needs for clinical diagnosis remains an unmet global challenge. Simple-to-use, sensitive, and rapid diagnostics are therefore urgently needed for early diagnosis of infection. The objective of this research is to design and demonstrate proof-of-principle of a novel low-cost and simple-to-use electrochemical sensing platform to enable rapid, ultrasensitive and accurate detection of SARS-CoV-2 virions in saliva (with accuracy ≥ 90% and total assay time < 30 min). We propose to achieve high sensitivity through two complementary signal amplification schemes, by electrophoretic concentration of virus-magnetic nanoparticle (mNP) conjugates by applying a small voltage on a set of electrodes with sub-micrometer gap, and amplifying electrochemical current through redox cycling between the same set of electrodes. Importantly, the proposed platform is suitable for commercialization by leveraging a low-cost and scalable fabrication method to create the sensor arrays without using expensive and non-scalable nanofabrication techniques. Fast, sensitive, and accurate detection of viral particles enables better surveillance and control of spread of the infection. The proposed platform is simple-to-use and suitable for point-of-care applications by eliminating tedious RNA extraction steps as in RT-PCR methods. It can enable high-throughput testing by creating sensor array on the same chip with small footprint to simultaneously analyze a multitude of sample droplets. The proposed sensory platform can also be expanded to detect other infectious pathogens, including Dengue and Influenza viruses, bacterial pathogens, etc.",2021,2024,N/A,590800,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15304,3U42OD010921-12S1,The Mutant Mouse Resource and Research Center at The Jackson Laboratory,"Abstract To date, most of the research using mouse models for COVID-19 has been done using a transgenic mouse model expressing high levels of the human ACE2gene driven by the Keratin-18(K18) promoter. While this model has been extremely useful, it has some notable limitations: disease progression is rapid and invariably fatal within one week, with an uncharacteristically high infection rate in the brain. These features restrict its use to study the biology related to the acute phase of the infection, leaving a gap in models that more accurately reflect the expression patterns and levels of the ACE2 receptor, and that extend the disease course beyond the acute phase of infection. We will employ a refined genetic strategy utilizing a recently published knock-in model of the human ACE2 cDNA into the mouse Ace2 locus. By crossing these hACE2 knock-in mice with inbred Collaborative Cross (CC) founder strains, and by characterizing the response of resulting humanized F1 progeny to live SARS-CoV-2 infection through an established partnership with researchers at the Trudeau Institute, we will test the hypothesis that clinical variation in COVID-19 patient response can be more accurately modelled and phenotypically characterized in mice with naturally regulated ACE2 expression on variable genetic backgrounds. Consistent with the aims of MMRRC parent grant to identify and distribute mouse models to the biomedical community, this proposal aims to rapidly provide the research community with an urgently needed resource for linking the variability in COVID-19 disease outcome with underlying host genetic features, and for developing precision models for post infection sequelae.",2021,2025,N/A,491863,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Post acute and long term health consequences,2021 +C15305,1R43AI165117-01,Point-of-care diagnostic for amplification and detection of SARS-CoV-2 RNA,"PROJECT SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has rapidly spread around the world. We propose the development of a diagnostic assay that will exhibit a low limit of detection of SARS-CoV-2 via a unique viral RNA amplification process. By developing a method to enrich viral RNAs over eukaryotic or bacterial RNAs we can lower the limit of detection and potentially reduce the level of false positives and negatives observed when using RT-based diagnostics. As this method is specific for viral RNA in general, it will can be used for other human ssRNA viral pathogens, such as Zika or Dengue. The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of a new step in viral RNA detection, usable for detecting SARS-CoV-2, but also other ssRNA viruses. By using an isothermal approach to amplify viral RNA our device will eliminate the need for expensive equipment, which increases access to testing. The proposed work will validate the specificity of the enzyme toward viral RNAs, develop a system to extract and detect these RNAs, and lower the detection limit for POC or at-home diagnostics.",2021,2022,N/A,260571,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15306,3R01MD013554-04S1,Medical Mistrust as a Barrier to COVID-19 and HIV Services Among Transgender Women of Color,"PROJECT SUMMARY This administrative supplement project seeks to study COVID-19 testing and vaccine uptake and HIV services (e.g., pre-exposure prophylaxis [PrEP] uptake and adherence) among transgender women (TW) of color (TWOC) in the New York City metropolitan statistical area (MSA). With this supplement, we will randomly enroll participants from the ongoing NIH-funded Trying To Understand Relationships, Networks and Neighborhoods among Trans women of color (TURNNT) Study (R01MD013554; PI: Dustin Duncan) in the quantitative phase of the proposed study (n=150) and the qualitative phase of the proposed study (n=40) to address the aims of the research. We are currently recruiting 300 Black, Latina and Asian TW in the TURNNT cohort using clinic- and community-based recruitment methods in partnership with Callen-Lorde Community Health Center (a major provider of healthcare for TW in NYC) and via venue-based recruitment (e.g., community organizations and dance clubs). The proposed project represents the largest study of COVID-19 in any population of TWOC to-date and presents a remarkable opportunity to study COVID-19 and HIV services among TWOC who experience intersectional stigmas and multiple forms of marginalization and inequality. This supplement will accelerate the science and impact of the parent grant, capitalizing on the existing TURNNT infrastructure and generate new knowledge that can be used to increase COVID-19 testing and vaccine uptake and HIV services, including by investigating the role of medical mistrust as a contributing factor for TWOC. This proposal is aligned with the administrative supplement and NIMHD's special attention to sexual and gender minority (SGM) populations and research on HIV/AIDS in populations that experience health disparities. This project will accelerate the science on COVID-19 and HIV disparities. This research will provide a context-specific and nuanced understanding of how social contextual factors, i.e. medical mistrust, may contribute to COVID-19 and HIV prevention and care behaviors in TWOC, which will in turn inform contextually appropriate HIV prevention and care interventions.",2021,2023,N/A,404281,Human Populations,Asian | Black | Other,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Gender,,,,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions | Health service delivery,2018 +C15307,3U01HL146205-03S1,Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies,"ABSTRACT MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV- infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative for their health that they be vaccinated with the new COVID-19 vaccines. To date, however, there are only anecdotal data on COVID-19 vaccine acceptance and efficacy in people with HIV (PWH). The MWCCS is ideal for analyzing (a) the acceptancy and effects of COVID-19 vaccine(s) in male and female PWH and matched HIV-uninfected controls (HUC), (b) the impact of age and co-morbidities on vaccine immune response and protection against COVID-19, and (c) the social, economic, and behavioral changes after COVID-19 immunization as compared to the individuals who opted to not take the vaccine. To address this issue, we will have 2 groups of MWCCS participants in this study: Group A: Male and female PWH and HUC who choose to receive a COVID-19 vaccine, Group B: Male and female PWH and HUC who choose NOT to receive a COVID-19 vaccine. The aims of our proposed longitudinal observational study for this OAR Innovation application are: Aim 1: To conduct an MWCCS-wide, mixed- methods investigation of the prevalence, correlates, and nuances of COVID-19 vaccine hesitancy among MWCCS participants. Results will help better understand the concerns of PWH and HUC populations regarding COVID-19 vaccines based on age, sex, race/ethnicity, and underlying comormidity burden. Aim 2: To determine the incidence of natural SARS-CoV-2 infections post- COVID-19 immunization in PWH as compared to HUC of the same age, sex, and ethnicity/race and also compare with the incidence of infections in non-vaccinated individuals. Because of budgetary limitations in the OAR Innovation Fund supplement, we will restrict Aim 2 to obtaining one specimen at baseline, just prior vaccination in Group A, and within comparable time periods for Group B. Subsequent samples collected during the core MWCCS visits will be used in the serological analyzes. These samples will allow us to determine the serological COVID-19 status pre-immunization, and post-immunization seroconversions for S and N proteins. The titration of anti-S responses post immunization will indicate vaccine immune response, while anti- N antibody titers will indicate natural SARS-CoV-2 infection This information will allow the identification of asymptomatic and symptomatic individuals infected with SARS- CoV-2 post- vaccination and in non-vaccinated group. The if these infections in the MWCCS will allow a targeted use of core samples in depth investigation of the immune mechanisms of vaccine- mediated protection, the immunologic responses and virologic characteristics of breakthrough SARS-CoV-2 infections, and the impact of the vaccination on underlying HIV infection. Importantly, timely funding from this OAR Innovation opportunity is critical to our addressing these aims prior to the broad rollout of the COVID-19 vaccines to our PWH participants. We are in a race to obtain this critical information and specimens prior to the wide availability of current FDA EUA vaccines to our MWCCS participants. The MWCCS clinical research sites across the United States and the data center are ready to launch this new study as soon as funding is available and we receive sIRB approval.",2021,2026,N/A,35088,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Characterisation of vaccine-induced immunity | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2019 +C15308,1R01AI158467-01,Optimizing a small molecule inhibitor of SARS-CoV-2 replication and associated cytokine storm,"Our goal is to develop towards an IND a novel class of small molecule inhibitors of phosphoinositide (PI) 4 kinase IIIb (PI4KIIIb) with potent dual activity against both SARS-CoV-2 and the excess cytokine release associated with COVID-19 disease. Entry of SARS-CoV has been shown to depend on PI4KIIIb, and strong inhibition of entry was achieved following knockdown of PI4KIIIb via siRNA, and SARS-CoV-2 is believed to enter cells via a similar mechanism. This likely reflects a requirement for enrichment of phosphorylated isoforms of PI, such as PI-4, in the lipid organelle required for viral fusion upon entry. We have developed potent and specific small molecule inhibitors of PI4KIIIb, and optimized them for high oral bioavailability. Our lead inhibitor, STF-1019 has nanomolar efficacy against enteroviruses (EV) which are also dependent on PI4KIIIb, and is the only molecule to have demonstrated in vivo efficacy in the animal model of EV-71, and without toxicity. We have now shown that STF-1019's EC50 against SARS-CoV-2 is 210 nM, with a CC50 of >100 microM, reflecting a therapeutic index (TI) of ~500. Finally, likely due to PI4KIIIb's role in Golgi-mediated secretion, we have also recently shown that STF-1019 can potently inhibit the LPS-induced secretion of IL-6 from human PBMC. STF-1019's metabolic stability, however, is suboptimal, requiring co-administration with an inhibitor (i.e. ritonavir) of its metabolism by CYP3A4 for optimal sustained tissue exposure. We hypothesize that: 1) STF-1019's SAR and major metabolites indicates that our lead PI4KIIIb inhibitor can be further optimized to increase its activity and metabolic stability to achieve an optimal exposure profile; 2) modifications that further increase PI4KIIIb inhibition can provide a buffer for modifications that may increase metabolic stability at the expense of efficacy; 3) the optimized inhibitor will inhibit SARS-CoV-2 in vitro, and in vivo; 4) the optimized inhibitor will have a high barrier to the development of resistance; 5) because of its orthogonal mechanism of action, our PI4KIIIb inhibitor can be used in combination with other agents to maximize efficacy; 6) STF-1019's inhibition of IL-6 reflects an ability to modulate the release of other cytokines, and this non- antiviral activity can be of great additional benefit in addressing the cytokine storm associated with severe COVID-19 infection; 7) determination of key pharmacokinetic, in vitro ADME-Tox parameters and initial preclinical in vivo toxicity assessment of our optimized lead can advance its translational development, and form the basis of a future IND package. We propose the test these hypotheses by: 1) Identifying the STF-1019 analog (and back-up compound) with greatest in vivo trough:EC90 ratios; 2) determining the in vivo activity of the optimized PI4KIIIb inhibitors against SARS-CoV-2 and their effect on cytokine production; 3) determining the relative barrier to resistance, and potential for synergy with other agents; and 4) nominating a PI4KIIIb inhibitor IND candidate by subjecting the optimized lead to initial in vitro ADME-tox and IND-enabling preclinical animal safety studies.",2021,2026,N/A,799024,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15309,1R21AI158278-01,MHC class II immunopeptidomics analysis of the SARS-CoV-2 proteome,"SUMMARY OF RESEARCH PROJECT COVID-19 is a global pandemic, the scope of which has not been seen in a century, and there is a critical unmet need for a vaccine to provide herd immunity against SARS-CoV-2. The objective of this proposal is to identify conserved immunodominant MHC class II peptides from the SARS-CoV-2 proteome that may be incorporated into current vaccine design studies. This meets a critical need to design a vaccine that will provide long-term protective immunity against COVID-19. This proposal uses an innovative immunopeptidomics platform to define the human SARS-CoV-2 MHC class II immunopeptidome using tandem mass spectrometry (Aim 1), and to determine CD4+ T cell responses to potentially immunogenic SARS-CoV-2 MHC-II peptides using a humanized mouse model (Aim 2). Robust CD4+ T cell responses to viral peptides are essential for establishing a pool of long-lived memory B cells and cytotoxic T cells. Results from this study will provide valuable insights into CD4+ T cell responses to viral proteins that may be rapidly incorporated into a vaccine design that will provide long-lasting protection from COVID-19.",2021,2023,N/A,234000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +C15310,3D43TW010046-06S1,Research Training for Substance Use Mediated HIV Epidemic in Kazakhstan,"The New York State International Training and Research Program (NYS-ITRP) at SUNY Downstate Health Sciences University proposes to train health care professionals on how to improve COVID-19 prevention and vaccination acceptance/access in people living with HIV (PLWH) in Almaty, Kazakhstan (KZ). To inform our training we will collaborate with our in-country Kazakhstan (KZ) partners, Kazakh National Medical University School of Public Health and Global Health Research Center of Central Asia, to assess COVID-19 vaccine attitudes and acceptance among 230 PLWH. The COVID-19 pandemic has had a substantial impact on morbidity and mortality, socioeconomic wellbeing and mental health. Since March 2020, over 375,000 cases of coronavirus infection were registered in KZ with >4,000 deaths. The pandemic has caused severe social disruption and dislocation in KZ, most significantly among PLWH. These effects include the disruption of HIV treatment services in KZ and potential negative impact on ART adherence and HIV treatment outcomes among PLWH. In addition, PLWH maybe vulnerable to suboptimal COVID-19 treatment and vaccine access. Finally, COVID-19 vaccine hesitancy in PLWH may be an additional barrier to adequate care. The specific aims of this proposal are to: 1) examine COVID-19 vaccine attitudes and acceptance among 230 PLWH in Almaty, KZ; and 2) develop and conduct a webinar for KZ's National AIDS Center health care professionals to improve knowledge on factors that contribute to COVID-19 vaccination acceptance among PLWH in KZ. In collaboration with our partners, a multidisciplinary team of KZ and US epidemiologists, clinicians and social workers, the project will study COVID-19 vaccine attitudes and acceptance among PLWH in KZ. This study will provide the critical data for our collaborators to create webinar content for health care providers in AIDS Center networks, with whom our partners have previously established collaborations. Webinar contents will focus on the pandemic's impact on PLWH, vaccine hesitancy and barriers to vaccination in PLWH, and health care worker communications with PLWH to overcome these barriers.",2021,2026,The New York State International Training and Research Program (NYS-ITRP) at SUNY Downstate Health Sciences University,80991,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,Europe,,,,Kazakhstan,Kazakhstan,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2016 +C15311,1R21AI161275-01,Identification of Host Directed Drug Targets for SARS-CoV-2 Using Transposon Mutagenesis,"SUMMARY The ongoing SARS-CoV-2 pandemic has brought into stark relief the need for novel therapeutics that can work against a broad spectrum of coronaviruses. Identifying essential host genes involved in both virus replication and antiviral defense could reveal key host-directed viral therapies that have the potential to work against SARS-CoV-2 and future coronavirus outbreaks. The overarching goal of our laboratory is to identify mechanisms of host defense against viral infections. This application aims to identify both host-encoded mechanisms of resistance to infection by SARS-CoV-2 as well as cellular factors critical for virus replication. Based on emerging data and our preliminary studies, our central hypothesis is that the up-regulation of host 'restriction factors' that prevent viral entry, constrain virus replication in host cells, or increase the ability of cells to withstand viral-induced cytopathy represent an important strategy in host defense. Our rationale for the proposed work is that identification of such factors will provide new targets for therapeutic intervention, and that these may be less susceptible to resistance than viral-encoded targets. We will use a novel forward-genetic approach to screen for host genes that confer resistance to SARS-CoV-2 infection in BSL3 using the native virus. This will allow us to identify key targets at all stages of virus infection. We will then validate new host targets and use these insights to rationally develop antiviral therapeutic strategies. Our screening approach is innovative because it allows identification of both host genes that confer resistance as well as host genes required for infection, which are normally detected in conventional RNAi-based screens. This work has the potential to identify new targets, including non-coding RNA elements, which would be missed using existing approaches.",2021,2023,N/A,442750,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C15312,1R21DE031166-01,Salivary gland response to innate immune mediators dictates Sjogren's syndrome development,"Project Summary Sjögren's syndrome (SS) is a systemic autoimmune disorder affecting multiple organ systems. A dysregulated immune response targeting the exocrine salivary and lacrimal glands reduces fluid secretion, which manifests into the dry mouth and dry eye symptoms of SS. Recent evidence in the literature suggests that innate immune activation is a prominent etiologic factor. Nevertheless, how a systemic or localized innate immune response transitions into an adaptive autoimmune response and targets the exocrine glands remains unclear. This issue is also highly relevant in the context of the ongoing COVID-19 pandemic. In genetically susceptible individuals, the systemic cytokine storm elicited by the SARS-CoV-2 infection and the salivary gland tropism of this virus may heighten the risk for developing SS or worsening its severity. The presence of lymphocytic infiltrates in exocrine glands is a significant feature of SS. These infiltrates are predominantly peri-ductal, suggesting that ductal cells are involved in initiating inflammatory cell infiltration into the salivary glands. By using the innovative collaborative cross mice and poly(I:C) as a surrogate for viral infection, this proposal will investigate how the genetic regulation of innate immunity in salivary gland epithelial cells (SGEC) influences SS development. We will test the overall hypothesis that in genetically susceptible individuals, the SGEC response to innate immune stimuli dictates lymphocytic infiltration into the salivary glands and SS development. To test this hypothesis, in Aim 1, we will investigate whether the hierarchy of systemic IFN responses in collaborative cross mice influences lymphocytic infiltration within the salivary glands. In Aim 2, we will investigate whether the genetic makeup of SGECs dictates the magnitude of their response to innate immune mediators. The successful completion of this proposal will help decipher the influence of a differential gradient of innate immune responsiveness in SS pathogenesis. Further, SS development in any of the collaborative cross mice used in this proposal will provide the SS research community a more patient-relevant model system to investigate gene-environment interaction(s) in the disease.",2021,2023,N/A,262200,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15313,1R01AG073627-01,Impact of COVID-19 on AD Occurrence: A Biracial Intergenerational Population Study,"The Chicago Health and Aging Project (CHAP) has made several significant contributions to Alzheimer's disease and related dementias (ADRD) epidemiology. These areas include racial disparities, prevalence, and incidence of dementia trends, social, lifestyle, vascular, genetic risk factors, and neuroimaging and blood biomarkers in a large population-based community study of African Americans (AAs) and European Americans (EAs). Using the older CHAP parent and the ongoing midlife offspring cohorts, we will test several novel and innovative hypotheses on the impact of COVID-19 on ADRD, MCI, cognitive decline, and structural MRI brain injury. By extending the awarded NIA NOSI Administrative Supplement, the intergenerational study provides significant advantages by investigating: (1) the direct effect of SARS-CoV-2 infections amongst those with higher inflammatory cytokines, especially in families with a high risk of COVID-19 transmission, which leads to adverse cognitive outcomes; and (2) an indirect effect of COVID-19 outbreak-imposed changes in physical and cognitive activities, social engagement, and vascular risk factors in a shared family environment in diverse communities. To address this scientific area of research, we propose to conduct a biracial population-based community study of 4,000 older CHAP parents with two population cognitive assessments and detailed clinical evaluations for ADRD in 1,200 participants with the following specific aims: (1) Estimate the 2020 US census demographic adjusted overall and demographic-specific (age, race/ethnicity, and gender) prevalence and incidence of ADRD, MCI, and dementia likelihood and test whether the prevalence and incidence have changed before and after COVID-19. Also, test whether the 5-year risk of ADRD among high-risk AA parents has high-risk offspring compared to EAs; (2) Examine the change in physical and cognitive activities, social engagement, BMI, and hypertension from pre- to post-COVID and the impact of these changes on the risk of ADRD, MCI, cognitive decline, and MRI brain injury. Also, test whether these associations are higher by age, sex (males vs. females), and among AA parents and offspring compared to EA parents and offspring; (3) Test whether participants with SARS-CoV-2 RNA infections and serology antibodies and elevated concentrations of inflammatory cytokines among those with higher vascular risk factors have a higher risk of ADRD, MCI, cognitive decline, and structural MRI brain injury. Also, test whether these associations are higher among AA parents and offspring compared to EAs. This proposal has an enormous public health impact in developing preventive strategies and therapeutic studies on the impact of COVID-19 on population health across generations from midlife to late-life in a diverse population with socially disadvantaged AA minorities.",2021,2026,N/A,3190519,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis | Indirect health impacts | Social impacts,2021 +C15314,3U01HL146242-03S1,SF Bay Area MACS/WIHS Combined Cohort Study,"This study complements the important ongoing MWCCS-wide COVID-19 study of vaccine hesitancy, compliance and uptake. Our mixed-methods approach (Aim 1) will leverage MWCCS core collection of vaccine uptake in order to establish temporal pathways and nuanced relationships between social position, medical mistrust, vaccine benefit mistrust, concerns about side effects, worries about corporate vaccine profiteering, and the preference for natural immunity. We will also build on existing core collection of general vaccine acceptance by 1) developing a new instrument assessing awareness of vaccine eligibility and access; 2) incorporating a vaccine communication instrument to better target messaging to high-risk populations; and 3) integrate a micronarrative component to explore in greater nuance individual-level factors that influence vaccine uptake decision-making, perceptions of vaccine communication strategies, vaccine distribution, and perceived vaccine hesitancy behaviors of the household and community. In addition, the data we propose to collect in the supplement could be leveraged after integration with COVID-19 core survey behavioral data to assess post- vaccine changes to COVID-19 prevention behaviors. This study will offer important insight into COVID-19 vaccine hesitancy and obstacles to vaccine acceptance, in addition to informing targeted communication strategies and intervention efforts that improve trust, increase uptake and break COVID-19 transmission dynamics among high-risk, aging populations with high comorbidity burden, exemplified in the MWCCS cohort.",2021,2026,N/A,44725,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15315,2R15GM127307-05,Biochemical characterization of a novel Fragile X Mental Retardation Protein nuclease function,"Project Summary Fragile X mental retardation syndrome is the most common form of inherited mental impairement, affecting ~ 1 in 4000 males and ~ 1 in 6000 females. The syndrome is caused by the loss of a normal cellular protein, named the fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein involved in the transport and translation regulation of specific messenger RNA (mRNA) targets. The mechanisms by which FMRP exerts its translation regulator function are not known, however it has been proposed that the protein works in conjunction with the microRNA (miRNA) pathway to regulate local protein synthesis in response to synaptic input. We have determined that FMRP has nuclease activity, being able to process precursor microRNAs (pre-miRNAs), potentially being involved in the mature miRNA biogenesis. This proposal, which will characterize this novel FMRP function, has the following specific aims: AIM I. Identification of the FMRP domain(s) responsible for its nuclease activity. We hypothesized that the FMRP nuclease activity resides in one of his K homology domains and to test this hypothesis we will produce several FMRP constructs lacking one or more of these domains. We determined that phosphorylated FMRP has higher nuclease efficiency than the unphosphorylated FMRP and we will test if this is caused by their different dimerization properties. Finally, we will also test if the FMRP paralogs, FXR1P and FXR2P, which share with FMRP the KH0, KH1 and KH2 domains, also have nuclease activity. AIM II. Biochemical characterization of the FMRP nuclease activity. We will determine if the pre-miRNA FMRP and its phosphorylated mimic can cleave pre-miRNAs into mature miRNAs. Additionally, we will determine if FMRP has additional substrates for its nuclease activity such as RNA perfect duplex, RNA single strand, RNA G quadruplex, DNA-RNA hybrid duplex, DNA duplex. Finally, we will characterize the kinetics of the FMRP nuclease. AIM III. Investigation of the FMRP interactions with the SARS-CoV-2 3'-UTR genome and of the potential role played by its nuclease activity in this viral system. Similar to its demonstrated role of restrictive factor in ZIKA virus infection, it has been proposed that FMRP might play a role in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus responsible for the current COVID-19 pandemic. We will test if FMRP cleaves various stem-loops within the SARS-CoV-2 RNA genomic 3'-untranslated region using its nuclease function either to potentially yield viral miRNAs or functioning in the antiviral host response.",2021,2024,N/A,414000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2005 +C15316,1R01AI169443-01,"Autonomously deploying, co-evolving SARS-CoV-2 antiviral: a new paradigm for pandemic prevention","PROJECT SUMMARY SARS-CoV-2, like all viruses, mutates and transmits; current medical countermeasures do not. This fundamental mismatch between dynamic viruses and our state-of-the-art static interventions means that vaccines and antiviral therapies often require frequent re-design and re-development, necessitating repeated (sometimes annual) resolutions to manufacturing and deployment challenges. Without fundamentally different forms of intervention to overcome this mismatch, future pandemics could rival or eclipse the catastrophic loss-of-life and economic impacts of SARS-CoV-2. To surmount the barriers thwarting current interventions, this proposal will engineer therapeutic molecular parasites of SARS-CoV-2 that can co-adapt and transmit among infected hosts. The key innovations of this approach are that these therapeutic parasites: (i) establish co-evolutionary arms races, co- evolving with wild-type virus to overcome resistance, (ii) replicate and self-renew, acting as single-administration therapies that circumvent compliance issues, and (iii) spread via the exact same risk factors and transmission routes as SARS-CoV-2-autonomously utilizing superspreaders to deploy the intervention-thereby circumventing manufacturing-at-scale and roll-out challenges. By design, these 'piggybacking' molecular parasites cannot replicate in uninfected hosts. Epidemiological models indicate that such molecular-parasite therapies would surmount the universal barriers to pandemic control and lower prevalence for many viruses below levels achievable by vaccination or antiviral therapy campaigns. The molecular rationale for developing molecular-parasite antivirals rests on ablating essential protein-encoding elements (i.e., trans-acting factors) to create conditionally replicating vectors that produce Therapeutic Interfering Particles (TIPs) when complemented in trans by wild-type virus superinfection. The crucial difference between TIPs and classical defective viral particles is that TIPs are engineered to have an R0 > 1-they efficiently mobilize, and transmit. As deletion variants, TIPs act as parasites, replicating only in virus-infected cells by stealing critical replication and packaging elements from the wild-type virus. By starving the wild-type pathogen of these critical elements, TIPs reduce wild-type pathogen levels. Critical feasibility precedents include that TIPs have been engineered to inhibit other viruses in vivo. Regulatory and ethical precedents include initial FDA clearances for HIV TIP Phase-I clinical trials supported by the NIH and DoD. This proposal will screen randomized synthetic libraries of SARS-CoV-2 variants to identify TIP candidates, test TIP efficacy and transmissibility in animal models, devise and test delivery and dosage formulations, and test tolerability, safety, and immunogenicity in a Phase-I clinical trial. The deliverable of this project will be the creation of a novel paradigm to counter SARS-CoV-2 and emerging pandemics by development and de-risking of an intervention that overcomes the universal barriers to infectious disease control.",2021,2024,N/A,2820494,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Phase 1 clinical trial,2021 +C15317,3R01DA049644-02S2,"Ethno-epidemiology of HCV, HIV and Overdose associated with Drug Markets and Drug Tourism","This competitive revision aims to increase access and uptake of COVID-19 testing and vaccination among people who inject drugs (PWID), a population highly vulnerable to COVID-19. The proposed RADxUP project, LinkUP, will be nested within the San Diego component of our parent grant, La Frontera, which was funded by NIDA in 04/20. To date, 31% of La Frontera PWID have tested SARS- CoV-2 antibody+, of whom 65% had not previously been tested for COVID-19. Only 3% had been vaccinated by 05/2021 and 45% were vaccine hesitant. Our specific aims are: AIM 1. To prospectively evaluate the prevalence, predictors and barriers to COVID-19 testing among PWID. AIM 2. To prospectively assess incidence, predictors and barriers to COVID-19 vaccination among PWID. AIM 3. To adapt and pilot an intervention offered at a mobile syringe services program (SSP) to improve uptake of COVID-19 testing and vaccination among PWID. AIM 4. To compare COVID testing and vaccination rates before and after the state introduces a) COVID-19 rapid testing and b) COVID-19 vaccination at the SSP, which represents a natural experiment. AIM 5. To prospectively assess the impact of COVID-19 testing and vaccination on PWIDs' behaviors. To meet Aim 1 and 2, we will conduct interviews with 400 PWID in La Frontera, results which will be available in Fall 2021. Based on these findings and input from our Community and Scientific Advisory Board (CSAB), we will select and adapt a brief intervention to improve COVID-19 testing and vaccination uptake among PWID at the mobile van of our community partner, OnPoint. The LinkUP intervention will then be piloted among a subgroup of 150 La Frontera PWID who have not received COVID-19 vaccine or testing and will be implemented by OnPoint peer counsellors, who will also offer on-site rapid COVID-19 antigen testing and confirmatory PCR and referrals to the closest COVID-19 vaccination center (until vaccine is offered at OnPoint by the state). We will evaluate COVID-19 vaccine uptake independently through ongoing La Frontera study visits that will include self-reported interview data, linkage of electronic health records with the San Diego County COVID-19 database, and by analyzing SARSCoV-2 antibody patterns to differentiate between natural infection and vaccine-induced immunity. Results will be used to estimate effect sizes for a future efficacy trial and shared with the RADxUP consortium, policymakers and program planners. Since there are 185 SSPs across the country, our study will inform efforts to enable SSPs to become important 'touchpoints' to reach marginalized PWID, strengthening the nation's pandemic preparedness infrastructure to reduce COVID-19 health disparities.",2021,2023,N/A,561819,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2021 +C15318,1R01NS124204-01,Brain pathophysiology in SARS-CoV-2 disease,"SARS-CoV-2, the virus underlying the current COVID-19 pandemic, not only affects peripheral tissues, it also targets the brain causing microvascular lesions, microhemorrhages and neurological manifestations. The internalization of SARS-CoV-2 is initiated by the binding of the virus spike protein to angiotensin converting enzyme 2 (ACE2) on the membrane of host cells including endothelial cells throughout cerebral capillaries. ACE2 is internalized along with the virus thereby leading to a state of ACE2 deficiency. ACE2 is a critical member of the renin-angiotensin system (RAS). This enzyme catabolizes the octapeptide hormone angiotensin-[1-8] thereby protecting cells and tissues from the vasoconstrictor, pro-inflammatory and pro-thrombotic effects of overactive angiotensin type 1 receptors (AT1Rs). Blocking AT1Rs with an AT1R antagonist protects mice from behavioral impairments due to ACE2 deficiency. Lipopolysaccharide (LPS) causes microglia activation and neuronal cell loss and is widely used as an experimental model of neuroinflammation. The brain pathophysiology induced by LPS shares many similarities with SARS-CoV-2 infection. We hypothesize that under conditions of reduced ACE2 (i.e., ACE2 knockout mice or SARS-CoV-2-infected hamsters), AT1R activity is upregulated in the microvasculature. In the presence of an inflammatory insult (i.e., LPS or SARS-CoV-2), AT1Rs promote endothelial dysfunction in the microvasculature through pro-inflammatory and pro-thrombotic signaling pathways leading to blood brain barrier injury. Deficits in cognition and increased anxiety ensue. We will test this overall hypothesis through the following specific aims: Determine the mechanisms of the pro-injury (Aim 1) and protective (Aim 2) arms of the RAS that regulate the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. (Aim 3) Determine the mechanisms underlying the effects of biological sex and age in the brain pathophysiology induced by LPS and SARS-CoV-2. Studying RAS mechanisms in the brain will provide insight into on-going and future clinical trials of therapeutics for treating brain injury associated with COVID-19 and other diseases of neuroinflammation. In addition, focusing on mechanisms underlying the effects of biological sex and age on microvasculature pathophysiology in models of neuroinflammation and COVID-19 will shed light into why male sex and age are major risk factors for COVID-19 severity.",2021,2026,N/A,661469,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Disease models | Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C15319,1K38AI163480-01,Systems Biology Approach to SARS-CoV-2 Infection in Individuals with known COVID-19 Contacts: A Prospective Cohort Study,"PROJECT SUMMARY/ABSTRACT With this K38 Mentored Stimulating Access to Research in Residency Transition Scholar (StARRTS) award, I will develop the necessary skills to become an independently funded clinician-scientist, working at the intersection of immunology, systems biology, and vaccinology. My longstanding commitment to translational and clinical research provides me with the foundation for this work. During this Award, I will be mentored by Dr. Nadine Rouphael, an expert in translational immunology, who is interim director of the Hope Clinic, the clinical arm of the Emory Vaccine Center, Dr. Bali Pulendran, an expert in systems biology at Stanford University, Dr. Erin Scherer, an expert in B-cell biology and director of the Hope Clinic Vaccine and Treatment Evaluation Unit (VTEU) Research Laboratory, and Dr. Christina Mehta, an expert in applied biostatistics in the Department of Biostatistics and Bioinformatics at the Rollins School of Public Health of Emory University. I will have hands on clinical research and biostatistical training as well as training in laboratory methods related to systems biology, and will attend workshops in the field. Currently, I am enrolling subjects for my R38 research year and using the combined diagnostic methods of anti-SARS-CoV-2 IgM/IgG testing and symptom-driven SARS-CoV-2 PCR testing to better identify individuals with asymptomatic and mild COVID-19. We hypothesize that a systems biology approach will identify specific baseline immunologic signatures, which predict COVID-19 disease acquisition and severity and that mild and asymptomatic COVID-19 will be characterized by a specific innate and adaptive immune responses. We propose a cohort study to complete the following aims: 1) To identify baseline immunologic markers predictive of COVID-19 disease acquisition and severity, and 2) To characterize the innate and adaptive immune responses to SARS-CoV-2 in individuals with asymptomatic and mildly symptomatic COVID-19. Completion of these aims will provide a better understanding of COVID-19 and position me to transition to independence as a clinician-scientist.",2021,2023,N/A,108886,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2021 +C15320,1R01AI161570-01,Broad-spectrum therapeutics against SARS-CoV-2 3CL protease,"PROJECT SUMMARY/ABSTRACT COVID-19 was first identified in December 2019 in Wuhan, Hubei province, China, resulting in the ongoing 2019- 2020 pandemic. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2). Common symptoms of the disease include fever, dry cough, shortness of breath, diarrhea, and loss of smell. Complications may include pneumonia, viral sepsis, and acute respiratory distress syndrome. As of today, other than remdesivir, there is no approved small molecule drug for the treatment of COVID-19 and the discovery of an effective vaccine remains uncertain. Our long-term goal is to develop antiviral drugs for the treatment of COVID-19 and human coronavirus infections in general. Our central hypothesis is that inhibition of SARS-CoV- 2 polyprotein cleavage results in the prevention and early treatment of COVID-19 before it progresses to its more severe form. We will identify nanomolar inhibitors of the CoV 3C-like protease (3CLpro) suitable to be developed as antiviral agents for the treatment of COVID-19 and other coronavirus infections. The proposal targets the 3CLpro, a key enzyme for SARS-CoV-2 polyprotein cleavage and viral replication. Our overall premise is that small molecule inhibitors targeting this essential viral enzyme will inhibit replication, and therefore have the potential to be of both preventive and therapeutic value. Thus, our primary objective is to design and develop structure-based small-molecule inhibitors targeting coronavirus 3CLpro using our established and proven drug discovery expertise. Guided by strong preliminary data, the inhibition of polyprotein cleavage hypothesis will be tested by pursuing three specific aims: Aim 1) To inhibit SARS-CoV-2 polyprotein cleavage by developing covalent peptidic inhibitors of 3CLpro (nsp5).; Aim 2) To inhibit SARS-CoV-2 polyprotein cleavage by developing noncovalent nonpeptidic inhibitors of 3CLpro (nsp5).; and Aim 3) To determine the efficacy of covalent and noncovalent SARS-CoV-2 3CLpro inhibitors in a golden hamster model. Under the first aim, lead compound 3150 and its analogs will be tested in viral and enzyme assays for inhibitory activity of SARS-CoV-2 3CLpro. An aqueous soluble form of 3150 will be evaluated in the animal model. Structure-based drug design approaches will be employed to optimize 3150 for binding to the crystal structure of SARS-CoV-2 3CLpro. Under aim 2, Structure-based virtual screening and hybrid ligand screening approaches along with medicinal chemistry will be used to prepare and evaluate noncovalent nonpeptidic inhibitors of 3CLpro. Under the third aim, top-ranked SARS-CoV-2 3CLpro covalent and noncovalent inhibitors will be tested for pharmacokinetics and efficacy in a golden hamster COVID-19 model. The ultimate goal of the proposed studies is to advance an anti-COVID-19 drug candidate to the stage of filing an investigational new drug (IND) application. Overall, the results of this project will have a significant positive impact because they lay the groundwork for the clinical development of COVID-19 antiviral therapy and the potential to combine a potent and selective protease inhibitor with a nucleoside analog (e.g., remdesivir) and if needed anti-inflammatory drugs (e.g., dexamethasone or baricitinib).",2021,2026,N/A,681379,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15321,1R21AI161230-01,Exploring the Coronavirus Exoribonuclease as an Antiviral Target,"Over the last 20 years, three major zoonotic coronavirus (CoV) infections have emerged all causing acute respiratory illness, leading to significant morbidity and mortality. SARS-CoV-1 emerged in Asia in late 2002 while Middle East Respiratory Syndrome (MERS-CoV) was first reported in Saudi Arabia in 2012. In late 2019, SARS-CoV-2 was reported in China and has now spread globally causing over 673,000 deaths in less than eight months. The currently-raging COVID-19 pandemic presents an urgent need to explore new targets and approaches. Many RNA viruses such as Hepatitis C virus (HCV) and Respiratory Syncytial virus (RSV) can be treated with ribavirin and other broad-spectrum antiviral nucleoside analogues. Ribavirin and other nucleoside analogues are misincorporated into progeny genomes by the virally encoded RNA-dependent RNA-polymerase (RdRp), resulting in lethal mutagenesis. Interestingly, ribavirin has minimal effect against SARS or MERS due to unique aspects of CoV replication. The 30kb CoV genomes are the largest of all RNA viral genomes, more than three times the typical size. All CoVs encode 16 non-structural proteins (nsps) required for the production of progeny RNA. Nsp14 contains an exoribonuclease domain (ExoN), which has been shown to ensure replication fidelity of the large genome and provide resistance to drugs like ribavirin. ExoN, a conserved 3' to 5' proofreading exoribonuclease, removes misincorporated ribavirin, rendering it ineffective. Active site mutants of human CoV ExoN result in severe defects in viral RNA synthesis. Thus, ExoN inhibitors are expected to be effective anti- coronavirus agents either as monotherapy or in synergistic combination with nucleoside analogues. This proposal aims to discover first-in-class ExoN inhibitors for further drug development. Our current program is focused on developing broad-spectrum small molecule inhibitors of essential viral exonucleases as antiviral drugs. These exonucleases, like CoV ExoN, possess an acidic active site containing dual magnesium ions that coordinate substrate binding and catalyze bond cleavage. This ExoN key structural motif presents an excellent opportunity to expand our antiviral program to CoVs. We have synthesized hundreds of herpesvirus exonuclease inhibitors tailored to the bi-metallic binding site, which will be evaluated for activity against bacterially expressed ExoN. We propose that inhibitors of ExoN proof-reading activity would exert strong antiviral effects as single agents and would powerfully synergize with ribonucleoside analogs such as ribavirin and remdesivir. Key outcomes of the work would be (1) establishing the druggability of the active site of ExoN for small molecule inhibitors, (2) determining the antiviral activity produced by direct ExoN inhibition, (3) evaluating the potential synergism between ExoN inhibitors and nucleoside analogs and (4) identifying lead candidates for follow on in vivo drug development efforts.",2021,2023,N/A,463700,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15322,3R01AI145687-03S1,Targeting early metastable intermediates of the SARS-CoV-2 spike for vaccine and therapeutics development,"TThe ongoing global pandemic of the novel SARS-CoV-2 coronavirus (CoV) presents an urgent need for development of effective preventative and treatment therapies. The viral-host cell fusion (S) protein spike is a prime target for such therapies owing to its critical role in the virus lifecycle. The S protein is divided into two regions: the N-terminal S1 domain that caps the C-terminal S2 fusion domain. Binding to host receptor via the Receptor Binding Domain (RBD) in S1 is followed by proteolytic cleavage of the spike by host proteases. This leads dramatic conformational transitions resulting in S1 shedding and exposure of the fusion machinery in S2, culminating in host-cell entry. Class I fusion proteins such as the CoV S protein that undergo large conformational changes during the fusion process must, by necessity, be highly flexible and dynamic. Indeed, cryo-EM structures of the SARS-CoV-2 spike reveal considerable flexibility and dynamics in the S1 domain, especially around the RBD that exhibits two discrete conformational states - a ""down"" state that is shielded from receptor binding, and an ""up"" state that is receptor-accessible. The overall goals of this study are to use our robust, high-throughput computational and experimental pipeline to define the detailed trajectory of the ""down"" to ""up"" transition of the SARS-CoV-2 S protein, identify early metastable intermediates in the fusion pathway, and exploit their structures and dynamics for identifying drug and vaccine candidates that target SARS-CoV-2. A wealth of structural information on CoV spike proteins, including recently determined cryo-EM structures of the SARS-CoV-2 spike, provides a rich source of detailed data from which to begin precise examination of macromolecular transitions underlying triggering of this fusion machine",2021,2022,N/A,771293,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies | Pre-clinical studies",2020 +C15323,3U01HL146202-03S1,MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS): COVID-19 Vaccine Acceptance and Hesitancy (CVHB) Study in People with HIV Supplement,"ABSTRACT MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV-infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative for their health that they be vaccinated with the new COVID-19 vaccines. To date, however, there are only anecdotal data on COVID-19 vaccine acceptance and efficacy in people with HIV (PWH). The MWCCS is ideal for analyzing (a) the acceptancy and effects of COVID-19 vaccine(s) in male and female PWH and matched HIV uninfected controls (HUC), (b) the impact of age and co-morbidities on vaccine immune response and protection against COVID-19, and (c) the social, economic, and behavioral changes after COVID-19 immunization as compared to the individuals who opted to not take the vaccine. To address this issue, we will have 2 groups of MWCCS participants in this study: Group A: Male and female PWH and HUC who choose to receive a COVID-19 vaccine, Group B: Male and female PWH and HUC who choose NOT to receive a COVID- 19 vaccine. The aims of our proposed longitudinal observational study for this OAR Innovation application are: Aim 1: To conduct an MWCCS-wide, mixed-methods investigation of the prevalence, correlates, and nuances of COVID-19 vaccine hesitancy among MWCCS participants. Results will help better understand the concerns of PWH and HUC populations regarding COVID-19 vaccines based on age, sex, race/ethnicity, and underlying comorbidity burden. Aim 2: To determine the incidence of natural SARS-CoV-2 infections post-COVID-19 immunization in PWH as compared to HUC of the same age, sex, and ethnicity/race and also compare with the incidence of infections in non-vaccinated individuals. Because of budgetary limitations in the OAR Innovation Fund supplement, we will restrict Aim 2 to obtaining one specimen at baseline, just prior vaccination in Group A, and within comparable time periods for Group B. Subsequent samples collected during the core MWCCS visits will be used in the serological analyzes. These samples will allow us to determine the serological COVID- 19 status pre-immunization, and post-immunization seroconversions for S and N proteins. The titration of anti- S responses post immunization will indicate vaccine immune response, while anti-N antibody titers will indicate natural SARS-CoV-2 infection. This will allow the identification of asymptomatic and symptomatic individuals infected with SARS-CoV-2 post-vaccination and in non-vaccinated group. The if these infections in the MWCCS will allow a targeted use of core samples in depth investigation of the immune mechanisms of vaccine-mediated protection, the immunologic responses and virologic characteristics of breakthrough SARSCoV-2 infections, and the impact of the vaccination on underlying HIV infection. Importantly, timely funding from this OAR Innovation opportunity is critical to our addressing these aims prior to the broad rollout of the COVID-19 vaccines to our PWH participants. We are in a race to obtain this critical information and specimens prior to the wide availability of current FDA EUA vaccines to our MWCCS participants.",2021,2026,N/A,39400,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15324,1F31AI164671-01,Suppression of Host Antiviral Responses by a SARS-CoV-2 Histone Mimetic,"PROJECT SUMMARY/ABSTRACT Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2) and has resulted in more than 1.4 million deaths globally. In contrast to other highly pathogenic influenza viruses, SARS-CoV-2 infection is characterized by low levels of type I interferons and over production of pro- inflammatory cytokines in patients. While concerted efforts have been made to understand the pathogenesis of this virus, how SARS-CoV-2 is able to evade the innate immune response is unclear. The central hypothesis of this proposal is that the envelope (E) protein of the virus interacts with BRD4 in a bromodomain-dependent manner to disrupt the induction of host innate inflammatory and antiviral responses. This hypothesis is supported by the recent proteomic study identifying this interaction and the presence of a histone H3-like motif containing two lysine residues in the E protein. This model is also strongly supported by previous studies demonstrating BRD4 as an important transcriptional coactivator of interferon and inflammatory genes during viral infection. The central hypothesis will be tested in two specific aims: 1) To define the role of bromodomains in the interaction between SARS-CoV-2 E protein and BRD4. The working hypothesis is that the lysine residues of the E protein are acetylated and mediate interaction with the bromodomains of BRD4, acting as a histone mimetic. I will test this model with label-free mass spectrometry to identify acetylated residues in E protein and immunoprecipitation assays with domain constructs to characterize the interaction. 2) To determine the functional relevance of the SARS-CoV-2 E protein and BRD4 interaction on the viral replication. The working hypothesis is that the E protein acts as a histone mimetic to sequester BRD4 from chromatin thereby disrupting the transcription of pro- inflammatory and interferon genes. I will use CRISPR/Cas9-mediated BRD4 knockout cell lines and BRD4 reconstitution studies in infected cells to test this model. My analysis will also focus on the transcriptional activation of canonical pro-inflammatory and interferon genes along with the chromatin occupancy of BRD4 in the presence of the E protein through RT-qPCR and ChIP-qPCR studies. I expect my proposed studies to inform our fundamental understanding of coronavirus pathogenesis and provide novel therapeutic targets to combat SARS-CoV-2 infection and immune evasion.",2022,2024,N/A,46036,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15325,1R21AI159666-01,Identifying and inhibiting the SARS-CoV-2 packaging mechanism,"Project Summary We aim to determine the molecular basis for SARS-CoV-2 viral packaging and to develop a screening strategy to identify inhibitors of this key step in the coronavirus infection cycle. Selective packaging of the viral genome, over more abundant transcripts, involves specific interactions between an RNA packaging signal, viral structural proteins and possibly other factors. Inhibition of this process would block formation of infectious virions and thereby contribute to a therapeutic regimen that would prevent or treat infection. Building on our laboratory's extensive expertise in RNA biochemistry and virus-like particle research, we propose to determine the functional SARS-CoV-2 packaging signal and to develop a robust small molecule-based assay for SARS-CoV-2 packaging inhibition. To determine the components of the SARS-CoV-2 packaging mechanism, we will generate virus-like particles (VLPs) that contain the structural proteins of the virus but not the viral genome. The absence of the genome renders these VLPs non-infectious and therefore safe to work with. Methods for generating these VLPs derive from published research with other coronaviruses as well as our own lab's experience working with influenza and HIV VLPs. SARS-CoV-2 VLPs will be produced by co-expressing the viral spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. RNA molecules containing the packaging signal can be packaged into these VLPs and delivered into receiver cells, providing an assay for packaging signal detection. In parallel, this approach will be used to establish a screening assay to identify viral packaging inhibitors. These two aims are independent, yet the results of each workstream will inform both the fundamental and applied aspects of the project. Our long-term objective is to develop a small molecule inhibitor of SARS-CoV-2 viral packaging. This approach has the following advantages: 1) we will naturally detect nucleocapsid inhibitors, which can be potent antiviral drugs as shown for HIV and other viruses due to strict constraints on nucleocapsid function; 2) our approach targets a step in the viral infection cycle that is not currently the focus of major therapeutic discovery efforts, enhancing the opportunity to find a new and/or complementary antiviral strategy; and 3) our screening approach does not require live virus and can be executed safely in most high-throughput screening facilities. The research proposed here will enable the development of new antiviral strategies for treating coronaviruses. SARS-CoV-2 is the third betacoronavirus to trigger a zoonotic outbreak in the last 18 years and estimates suggest that ~5000 related viruses are circulating within bat populations around the world. Our proposal targets a critical yet relatively understudied step of the coronavirus life cycle that is a promising target of selective small- molecule inhibition. The results of this work will inform and enable other viral inhibition efforts and provide a basis for future high-throughput drug discovery initiatives.",2021,2023,N/A,519750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15326,3R01NR017644-03S1,"A pragmatic, scalable e-health intervention for management of gestational weight gain in low-income mothers","PROJECT SUMMARY The SARS-CoV-2 (COVID-19) pandemic is adversely impacting the physical and mental health of non- pregnant people, including weight gain and increased sedentary behavior, depression, anxiety, and stress. The overarching goal of this administrative supplement to A pragmatic, scalable e-health intervention for management of gestational weight gain in low-income mothers (R01NR017644), is to expand these observations into pregnant and postpartum populations with the long-term objective of understanding the impact of the COVID-19 pandemic on perinatal physical and mental health outcomes among women who were pregnant during the pandemic and to identify mediators of this impact. The central hypothesis is that exposure to the COVID-19 pandemic during pregnancy will be associated with worsened perinatal physical and mental health outcomes. The specific aims are: 1) examine the effects of the COVID-19 pandemic on gestational weight gain among pregnant women in Louisiana, 2) investigate the effects of the COVID-19 pandemic on racial disparities on adverse pregnancy outcomes among women pregnant during the pandemic in Louisiana, and 3) examine the effects of the COVID-19 pandemic on perinatal mental health among women pregnant during the pandemic in Louisiana. Louisiana is a living laboratory for the country and the world, with an expansive spectrum of income and education levels, and high racial diversity. The specific aims will be tested with two unique study designs. First, a retrospective chart review of deliveries at Woman's Hospital (Baton Rouge, Louisiana) will be used to compare gestational weight gain and pregnancy outcomes from women who were pregnant during the pandemic, compared to women who were pregnant immediately before the pandemic (n=~23,000); as well as comparing outcomes between Black and White women. Second, using a sequential explanatory mixed-methods design we will survey and interview two cohorts of recently postpartum women who were pregnant during the pandemic about their mental health as well as pandemic-related hardships: Louisiana WIC recipients and patients of Woman's Hospital. The mixed-methods design offers rigor by integrating components of triangulation, complementarity, expansion, and development. The project survey includes validated mental health questionnaires and common data elements of the NICHD Promoting Data Harmonization to Accelerate COVID-19 Pregnancy Research. Potential mediators are pandemic-related hardships, including isolation and changes to government assistance, housing, employment, or access to medical care. At the end of the project, our expected outcome is to have quantified the impact of the COVID-19 pandemic on the physical and mental health of pregnant and postpartum women and identified mediators of that impact.",2021,2023,N/A,699510,Human Populations,Black | White,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Digital Health,,,,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2018 +C15327,3K23HL129888-05S1,Mechanisms & risk factors of chronic lung disease in HIV+ adolescents in Nairobi,"PROJECT SUMMARY/ABSTRACT As increasing numbers of children with HIV are surviving to adolescence in low- and middle-income countries, chronic lung disease (CLD) has emerged as an important but poorly understood complication amongst adolescents and young adults living with HIV (ALWH). In the ongoing, longitudinal BREATHE II Study (K23 HL129888, PI Attia) in Nairobi, Kenya, 19% of 162 ALWH have abnormal spirometry compared to 11% of 162 uninfected participants; 59% of ALWH have ≥1 abnormality on high-resolution chest CT scan, with mosaic attenuation among the most common. Chronic respiratory symptoms are also highly prevalent among 62% of ALWH and 49% of uninfected participants. HIV is independently associated with impaired lung function, and risk factors for impaired spirometry among ALWH include inhaled exposures, such as secondhand smoke and ambient fine particulate matter, as well as growth deficits. Objectives of the K23 research include: examining differences in risk factors and mechanisms of CLD progression over time; determining the role of HIV infection on change in lung function over time, considering the complex interplay with other risk factors; and, evaluating whether biomarkers of chronic immune activation and inflammation are associated with diminished lung function growth over time. However, in light of the COVID-19 pandemic, these longitudinal studies have been halted for safety reasons. As these studies can now resume with added precautions, an Administrative Supplement to this K23 will provide essential resources for the following Aims: 1) complete longitudinal lung function and clinical data collection to conduct planned analyses as proposed in the parent K23; 2) add testing for COVID-19 both to mitigate risk of potential spread of SARS-CoV-2 through spirometry (rapid PCR test) and to examine the role of COVID-19 infection on lung function growth and development (serologic antibody test). The indispensable support of this Supplement will maintain the BREATHE II cohort, a unique and innovative resource for understanding CLD progression among ALWH, especially those with perinatal HIV acquisition, compared to demographically similar uninfected participants from the same geographic catchment area in the context of COVID-19. This cohort includes a dataset of chest CTs that is larger than in any published literature to date. Serum for biomarker analysis (currently underway) has the potential to inform mechanistic pathways of CLD. The study infrastructure is already supporting implementation of sub-studies to obtain quantitative measures of air pollution exposure and to compare CLD in BREATHE II to a cohort of ALWH in a high-income setting, and is a well-positioned platform to support future sub-studies. Findings of this research will provide critical data for informing R01-level research to investigate novel insights into the pathophysiologic mechanisms of CLD progression in ALWH in resource-limited settings, shedding light on risk factors and mechanisms that can be targeted by preventative and therapeutic interventions to mitigate the burden of CLD.",2021,2022,N/A,79072,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Africa | Americas,Data Management and Data Sharing,,,,United States of America | Kenya,Epidemiological studies | Clinical characterisation and management,"Disease surveillance & mapping | Disease pathogenesis | Supportive care, processes of care and management",2017 +C15328,3R01NR018837-02S1,The Impact of Telelactation Services on Breastfeeding Outcomes among Minority Mothers: Siteless Tele-MILC Trial,"Project Summary Breast milk is the best source of nutrition for infants, and breastfeeding offers numerous medical advantages for parents and infants. However, the COVID-19 pandemic has erected new barriers to breastfeeding, undermining important gains in breastfeeding initiation and duration that the U.S. has achieved in recent years. Key barriers include reduced breastfeeding support services and social support, and increased stress and postpartum depression, which can lead to early breastfeeding cessation. Further, pregnant and breastfeeding parents, who are at heightened risk of COVID-19 morbidity and mortality, now face complex decisions regarding COVID-19 vaccination given vague clinical recommendations for these populations. This study leverages an existing siteless randomized controlled trial on the effectiveness of telehealth for breastfeeding support (telelactation) among minority parents and will field a new cross-sectional survey to 1500 additional parents to collect data about the impact of COVID-19 on breastfeeding support, including use of telelactation, and vaccination. As part of the already funded clinical trial, 1200-1500 parents, including approximately 900 minority parents, will be recruited using the Ovia pregnancy app to participate in a trial evaluating telelactation services. This longitudinal study, which recruits participants starting in May 2021, coupled with a cross- sectional survey that will collect comparable data on the experiences of 1500 postpartum parents prior to and in the early months of the COVID-19 pandemic, offers an unparalleled opportunity to assess how the pandemic has impacted breastfeeding support, including use of telelactation, and how attitudes about the COVID-19 vaccine change over time as the vaccine supply grows and clinical recommendations become more directive. The project aims to 1) assess how the pandemic has impacted the provision of professional breastfeeding services and lay support and how changes have influenced breastfeeding experiences; and 2) track changes in attitudes about COVID-19 vaccine, willingness to be vaccinated, and timing and receipt of vaccination as the pandemic progresses. This study will provide important information on the impacts of the COVID-19 pandemic on breastfeeding experiences and track vaccine attitudes in a high-risk population that is typically excluded from clinical vaccine trials. With a cross-sectional survey to establish baseline trends and ongoing data collection through a longitudinal study, we can explore how key breastfeeding facilitators change over time and how diverse populations of parents are making decisions about vaccination. This information will help inform public health strategies and clinical practice to support new parents and to reduce disparities in breastfeeding duration and vaccination rates.",2021,2025,N/A,149487,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Digital Health,,,,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2020 +C15329,3U19AI110483-08S4,ACE Covid 19 Admin Supplement: Molecular Regulation of B cells and T cells in Human SLE,"COVID 19 Vaccination Trial (ACV01) Emory requests an Admin Supplement (AS) to support the ACE COVID-19 vaccination trial (ACV01) and study. Below, first the major components are listed and described briefly, then budgeting details are provided. There are three major components of the AS: 1. ACV01 interventional clinical trial of COVID-19 vaccines in patients with autoimmune diseases. a. $10 M completed protocol with investigators, sites, and detailed budget for first cohorts (5 autoimmune diseases, 3 therapies, 3 vaccines). b. $10 M additional for the 'adaptive' cohorts that will be identified within the first half year. c. The protocol for the initial cohorts is complete and under review at FDA (anticipated July 12). d. Appendix: protocol 2. Statistical and Clinical Coordinating Center support (Rho Federal Systems) a. $4.5 M for subcontracting from Emory to Rho after their contract ends April 30, 2022. b. Rho will submit separately a detailed budget ($4 M expected) for support during the initial period. 3. ACV02 observational clinical study of COVID-19 vaccines in patients with autoimmune diseases. a. $2 M completed research plan protocol with lead investigators and sites; additional investigators will be recruited. b. The budget is currently scaled-up from a few essential procedures, such as blood draws, antisera measurements, and processing and storage. c. The samples will be used in more sophisticated assays later, which are beyond the scope of the current program and not supported by the current budget. d. Appendix: research plan Total request = $26 M The ACV01 clinical trial will enroll patients with 5 different autoimmune diseases (SLE, RA, MS, SSc, Pemphigus) on 3 different immunosuppressive therapies (aCD20, MTX, MMF) being randomized to several trial arms (e.g., withholding therapy during vaccination) to be vaccinated using one of at least 3 major vaccine providers (Pfizer/BioNTech, Moderna, Janssen, others expected). Patient visits are priced by combination of 4 parameters: disease + therapy + vaccine + arm of trial. The disease- and therapy- specific details are currently estimated based on visit time, personnel, and nature of the assessments.",2021,2022,N/A,26794157,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Phase 3 clinical trial | Phase 3 clinical trial,2021 +C15330,3R01HD103684-01S1,Community Events and Pathways to Inequities in Birth Outcomes,"PROJECT SUMMARY/ABSTRACT This urgent competitive revision will address how two public health emergencies-COVID-19 and racism-have impacted Black maternal health. The overall objective of the parent project is to elucidate the association between a pervasive form of structural racism-racialized police violence-and adverse reproductive health outcomes. This time sensitive request has significant potential to further revolutionize our understanding of the impact of racism on Black maternal health by exploring how the dual pandemics of COVID-19 and structural racism laid bare by George Floyd's death while in police custody have impacted Black maternal health. The proposed urgent revision enhances the current R01 by adding two aims to address the implications of the events of 2020-the COVID-19 pandemic and the death of George Floyd while in the custody of Minneapolis Police and the ensuing civil unrest-for Black maternal health. Aim 1 (a) quantify the impact of George Floyd's death on trends in preterm birth (PTB) and low birth weight (LBW); (b) quantify the risk of PTB and LBW related to spatial proximity to the death of George Floyd by Minneapolis police and the ensuing civil unrest; and (c) explore if the COVID-19 pandemic moderates the relationship between the death of George Floyd and risk of PTB and LBW. Preterm birth (<37 weeks gestation) is a critical marker that is sensitive to the well-being of a community-in regard to racism and measures of stress. Thus, PTB can reveal a lot about how the traumatic death of George Floyd and the stress of COVID-19 have played out in the lives of pregnant Black women. Aim 2: Illuminate the lived experience of how the dual pandemics of COVID-19 and structural racism (laid bare by George Floyd's death) have impacted Black women who were pregnant in 2020. The revision will enhance the scope and sample size of the parent grant online survey of Black women who were pregnant and living in the two communities that are the focus of the parent R01 (Minnesota and Louisiana) to assess psychosocial stress related to George Floyd's death, the COVID-19 pandemic, and structural racism. We will also conduct 25 in-depth interviews with Black women in Minnesota who complete the survey to illuminate Black maternal health outcomes for women living in the community where George Floyd died. This timely and urgent revision proposal is directly responsive to Area 2 of NOSI NOT-OD-21-071: Investigate the impact of structural racism in the context of the COVID-19 pandemic on the health and well-being of persons during pregnancy and up to one year postpartum. The proposed aims extend in significant and innovative ways the overarching goal of the parent R01; the timing and severity of the COVID-19 pandemic and the death of George Floyd could not have been anticipated at the time of the original proposal. Both the funded project and revision request mark an important change in public health framing from one that incorrectly names race-a seemingly immutable characteristic-as a ""risk factor"" to one that identifies racism as a fundamental cause of health inequities.",2021,2025,N/A,346456,Human Populations,Black,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Health Systems Research,Health service delivery,2021 +C15331,1R01AI159260-01A1,MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes,"SUMMARY Located within the human Major Histocompatibility Complex (MHC) chromosome 6p21, the Human Leukocyte Antigen (HLA) region is the most medically important region of the human genome. Variation in the HLA region has been associated with over 150 diseases and conditions, including infectious disease, cancers, and major drug-hypersensitivities. While little is known at this point about the impact of host genetic factors in COVID-19, the epidemiology to-date reveals wide variation in disease course among confirmed cases of infection that does not appear to be fully explained by known risk factors. Because of its pivotal role in the immune response understanding the role of HLA variation promises to provide important insights relevant to understanding the immunopathogenesis of COVID-19, while informing vaccine development and potential immunotherapies. In Specific Aim 1, we will exploit an existing data resource, partnering with the National Marrow Donor Program and DKMS registries to collect data on COVID-19 symptoms, testing and outcomes using a novel, validated smartphone app in a very large sample (N=300,000-500,000) of volunteer bone marrow donors with pre-existing HLA genotyping data, allowing an extraordinarily well-powered examination of the role of these genes in disease. In Specific Aim 2, we will employ a novel, validated method for next-generation sequencing of the extended MHC (~5Mb), including all classical and non-classical HLA loci, as well as over 150 additional immune system loci, in large and diverse cohorts of COVID-19 patients (N=2000), as well patient cohorts with longitudinal clinical data and extensive immunoprofiling (N=300). Finally, in Specific Aim 3 we will contextualize these association studies through examination of the role of HLA presentation of SARS-CoV-2 antigens. In summary, we will leverage large and diverse patient cohorts alongside cutting edge technology and molecular biology to reveal the role of these important immune loci in COVID-19.",2021,2026,N/A,809466,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +C15332,3R01AI095366-08S1,Rapid Generation of Vaccine Candidates Against Novel Coronavirus (SARS-CoV-2) Using the Bacteriophage T4 Nanoparticle Platform,"PROJECT SUMMARY This proposal aims to rapidly generate vaccine candidates against the 2019 novel coronavirus SARS-CoV- 2. Since its emergence about three months ago, this virus has caused more than 120,000 infections and 4,300 deaths worldwide and is rapidly spreading to virtually every country including the United States. This global health emergency must be immediately addressed by rapidly developing medial countermeasures. Our bacteriophage (phage) T4 vaccine platform is uniquely suited to address this threat. Developed in PI's laboratory, the T4 vaccines have been proven to generate robust humoral as well as cellular immune responses and confer complete protection against anthrax and plague in multiple animal models including mice, rats, rabbits, and macaques. The T4 vaccines do not need an adjuvant as its surface structure mimics the Pathogen- Associated Molecular Patterns (PAMPs) of viral pathogens and stimulate strong innate and adaptive immunity. The 120 x 86 nm phage T4 capsid is packaged with 171 kb genome and decorated with two non-essential outer capsid proteins; 870 molecules of Soc (small outer capsid protein) and 155 copies of Hoc (highly antigenic outer capsid protein). In specific aim 1, a series of T4-corona phages will be constructed by incorporating SARS- CoV-2 virion components individually and in combinations, by CRISPR engineering. The gene encoding the entire spike ectodomain will be inserted into phage genome under the control of the strong CAG promoter. Upon immunization, host cells (myocytes and antigen presenting cells at the site of immunization) take up phage particles and secrete the ectodomain trimers continuously, stimulating the immune system for weeks to months. The gene for the receptor binding domain (RBD) of S protein will be inserted such that the RBD will be expressed in host cells, as well as in E. coli as a Soc fusion protein which will then be displayed on phage capsid up to 870 copies per capsid. The ectodomain of E protein will be fused to Hoc and displayed up to 155 copies per capsid. Finally, ~400 copies of N protein will be packaged inside the capsid as part of the scaffolding core. In specific aim 2, the above T4-corona recombinant phages will be evaluated for elicitation of SARS-CoV- 2 virion-specific immune responses in a mouse model. Mice will be immunized with purified phage particles intramuscularly and the immune responses will be quantified by ELISA, competitive receptor binding, ELISpot, and virus neutralization assays. We expect that the T4-corona vaccines will elicit robust antibody and cellular responses and also inform which candidate(s) will be most effective in blocking SARS-CoV-2 infection. We have streamlined the CRISPR engineering such that the proposed T4 vaccines can be constructed in about 4 weeks and the animal testing can be completed in about 12 weeks. The candidate vaccines will then be available for clinical trials and vaccine manufacture. The T4 vaccine will be exceedingly easy to manufacture, scale, and distribute globally, and could potentially lead to a breakthrough to avert the coronavirus crisis.",2021,2022,N/A,30170,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +C15333,1R21AG074179-01,The Role of COVID-19 Endothelial Cell Dysfunction and Hypercoagulability in the Development of Post-ICU Cognitive Impairment and Dementia,"Project Summary/Abstract About 5-8% of those who are infected with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) require intensive care unit (ICU) hospitalization for severe coronavirus 2019 (COVID-19) symptoms. More than 80% of COVID-19 ICU patients develop delirium, an acute disorder of attention and cognition, placing them at higher risk for mild cognitive impairment (MCI) and Alzheimer's disease and other related dementias (ADRD). Research is urgently needed to identify novel therapeutic targets which may reduce the potential public health burden of ICU delirium and subsequent ADRD from the COVID-19 pandemic. One such promising therapeutic target may be endothelial cells, which can be directly infected by SARS CoV-2. Endothelial cells line the blood vessels and play a crucial role in the regulation of inflammation and blood coagulation. When these endothelial cells are infected by SARS CoV-2, patients can develop acute inflammation and changes in the blood to form blood clots throughout their various organs (also known as hypercoagulability). However, a major knowledge gap is whether COVID-19 associated endothelial cell dysfunction can explain how certain brain disorders, such as delirium and ADRD, arise in COVID-19 ICU patients. Studies are also needed to understand whether inflammation and hypercoagulability from COVID-19 associated endothelial cell dysfunction may explain the link between delirium and subsequent ADRD. To answer these questions, we propose to conduct a prospective pilot study that will compare ICU patients hospitalized for severe COVID-19 symptoms with ICU patients who are not infected with SARS CoV-2 hospitalized for acute respiratory failure and shock. The overall hypothesis is that endothelial infection with SARS CoV-2 causes endothelial cell dysfunction and accompanying inflammation which, in turn, trigger a hypercoagulable state. This COVID-19 associated pathophysiology initially manifests as ICU delirium, and persists to cause ongoing cerebrovascular damage, neurodegeneration, and, finally, ADRD. The goal of this proposal is to estimate the strength of these associations for the following aims that will be the groundwork for a future R01 proposal: 1) examine the differences in endothelial cell dysfunction, inflammation, and hypercoagulability between COVID-19 and non-COVID 19 ICU patients; 2) determine whether COVID-19 associated endothelial dysfunction, inflammation, and hypercoagulability are associated with higher rates of ICU delirium and/or MCI and ADRD; and 3) examine the relationship between COVID-19 associated endothelial cell dysfunction, inflammation, and hypercoagulability and biomarkers of neurodegenerative disorders.",2021,2023,N/A,198125,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15334,1R01DK132735-01,Metabolic and epigenetic reprogramming of vital organs in SARS-CoV-2 induced systemic toxicity,"Project Summary/Abstract SARS-CoV-2 primarily affects the respiratory system but extra-pulmonary manifestations in individuals with COVID-19 are commonly seen. All major organ systems have been reported to be affected by SARS-CoV-2 and complications arising from ensuing organ dysfunction significantly increase the mortality rate of COVID-19. Yet, despite the clinical importance of systemic involvement of SARS-CoV-2, little is known about the pathogenesis of extra-pulmonary complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi-organ involvement and investigate the role of metabolic and epigenetic reprogramming of vital organs in the pathogenesis of systemic toxicity of COVID-19. We demonstrate that following a robust anti-viral immune response, there is metabolic suppression of oxidative phosphorylation and the tri-carboxylic acid (TCA) cycle in multiple organs. The animals develop a profound phenotype within 7 days of SARS-CoV-2 infection with severe weight loss, morbidity and failure to thrive. Examination of multiple internal organ systems demonstrated neutrophilia, lymphopenia, splenic atrophy, with cardiomyocyte cell death, myocardial edema and extreme myofibrillar disarray observed in the heart and mirroring reported human clinical phenotypes in COVID-19. An organ wide metabolic reprogramming consistent with depression of oxidative phosphorylation leads to utilization of peripheral fat stores and gross accumulation of fat in the heart, kidney, liver and other vital organs. We perform metabolomic profiling of peripheral blood and identify a panel of TCA cycle metabolites that serve as biomarkers of depressed oxidative phosphorylation, several of these markers been noted in human clinical studies to be associated with adverse prognosis. Finally, we demonstrate that despite the absence of viral genomes in tissues, transcriptional changes persist and are associated with significant differentially methylated regions in vital organs across the host cell genomes. Considering these observations, we dissect the mechanistic basis of such metabolic reprogramming in SARs-CoV-2. We have created a multi-disciplinary team comprising, metabolomics experts, virologists, physiologists and geneticists to study metabolic fluxes and organ wide transcriptomics to study in the depth the role of metabolic and epigenetic reprogramming in causing SARS-CoV-2 induced severe systemic toxicity.",2021,2024,N/A,3636473,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15335,1R01AI161363-01,Mechanism-based Targeting of the RNA Processing Machinery of SARS-CoV-2,"ABSTRACT The massive global pandemic with high morbidity and mortality makes Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) one of the deadliest viruses in recent history. It is especially noteworthy for hijacking the normal operations of human cells. To develop effective therapies, we need a better understanding of the mechanisms that permit the virus to invade cells and evade host immune restriction. SARS-CoV-2 encodes the non-structural protein (nsp)16/nsp10 protein complex that transfers a methyl group from S-adenosyl methionine (SAM) to 2'-OH of the first transcribing nucleotide of the viral mRNA and thus converts the Cap-0 (m7GpppA) to Cap-1 (m7GpppAm). The resulting viral mRNA mimics host cell's mRNA. In this way, a cell cannot distinguish between its own RNA and that of the virus. This modification of the virally encoded mRNA not only tricks the immune system and helps the virus to take over the host translation machinery for synthesis of its own proteins for survival and propagation. Ablation of nsp16 activity should trigger an immune response to viral infection and limit pathogenesis. Our recent paper in Nature Communications described atomic level details of the nsp16/nsp10 complex and how the enzyme is well adapted to bind the RNA cap and exert the 2'-OH methylation. We also discovered a distant pocket (located 25Å away from the catalytic center) in nsp16 that is unique to SARS-CoV-2. We also found that this pocket in nsp16 is partially composed of amino acids that are unique to SARS-CoV-2. It can bind small molecules outside of the catalytic center. We propose to build a long- term research program aimed at deciphering the factors crucial to the maintenance of RNA genome and evasion from the host's immune response. Our studies will reveal basic principles underlying SARS-CoV-2 RNA cap modification, the mode of nucleoprotein (NP) assembly, interplay with mRNA, and new approaches for therapeutic targeting. In Aim 1, we will resolve a series of new structures of nsp16/nsp10 proteins captured in every step of the methyl transfer by X-ray crystallography. The structural data will be validated by detailed biochemical and biophysical studies. We will resolve the biochemical and structural determinants of the assembly of viral RNA capping machinery, and identify factors underlying integrity of RNA genome. In Aim 2, we will develop a novel molecular tool to study temporal distribution of the RNA methylation during viral infection. We will examine new models for combinatorial inhibition of viral proteins by drug repurposing or novel small molecules. Finally, we will use our recently established reverse genetics approaches based on the use of a bacterial artificial chromosome (BAC) to generate recombinant (r)SARS-CoV2 containing mutations in nsp16 to determine their contribution in viral replication in cultured cells and pathogenesis in vivo using our recently described K18 human angiotensin converting enzyme 2 (hACE2) mouse model of SARS-CoV-2 infection and associated coronavirus disease 2019 (COVID-19).",2021,2026,N/A,608161,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity | Disease models",2021 +C15336,3U54MD013376-03S1,RCMI@Morgan: Center for Urban Health Disparities Research and Innovation,"PROJECT SUMMARY The goal of this HIV/HCV/COVID-19 supplement project is to expand the original study cohort for studying (1) the feasibility of and barriers to achieving HCV elimination among people living with HIV (PLWH) and people at risk of HIV (PARH) through linkage to HIV care and prevention and (2) the impact of COVID-19 pandemic and lockdown on HIV and HCV continuum of care and health outcomes. The original study cohort included HIV- infected men engaged in HIV primary care at a large, multisite community health center from 2003 to 2014. In this supplement project, we will expand the study cohort, from 2014 to 2024, and include additional minorities of PLWH and PARH receiving HIV care or HIV pre-exposure prophylaxis (PrEP), respectively, at the clinics of this community health center, such as women, transgender women/men, and rural dwellers. In addition, we will extend the study sites to include a large multi-hospital healthcare system, with which my lab has established a formal research partnership through the ongoing NIMHD-supported COVID-19 supplement project. The HIV clinics of the community health center and the healthcare system are situated in urban and suburban Baltimore and rural Maryland with major health disparities and provide HIV care and preventive services to people of racial, sexual, and/or gender minorities and other socioeconomically disadvantaged populations. Based on the findings from the original cohort, we hypothesize that (1) elimination of HCV health disparities and disease burdens could be achieved for the PLWH and PARH by engaging in HIV care or preventive services, respectively, and (2) certain circumstances and determinants could pose barriers to achieving this anticipated result. We will perform a longitudinal retrospective cohort study with data derived from the medical records to assess various aspects of HCV infection and care among the PLWH and PARH. First, we will determine trends and factors associated with surveillance testing, prevalence, incidence, treatment initiation and completion, eradication, and re- occurrence of viremic HCV among the PLWH and PARH. All of these HCV-related outcome measures (referred as to the ""HCV elimination package"") will be analyzed in the context of continuum of HIV care or PrEP usage and other HIV-related virologic and immunologic parameters. Next, we will assess the HIV continuum of care during the COVID-19 pandemic, analyzing the trends and factors associated with missing appointments, labs, and/or prescriptions as well as utilization of telehealth for HIV care and preventive services. We will also examine the HIV-related health outcomes among the PLWH and PARH prior to, during, and after the pandemic. Similarly, each of the measures involved in the ""HCV elimination package"" will be assessed to determine the impact of COVID-19 lockdown and HIV care/preventive service interruption on HCV elimination endeavours. Finally, we will use the ongoing study cohort of >5,600 hospitalized COVID-19 patients in this multi-hospital health care system to delineate the clinical features and determine factors associated with COVID-19 pathogenesis, disease severity, and treatment outcomes among those with and without HIV and/or HCV coinfections. PROJECT SUMMARY",2021,2023,N/A,271599,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts,2019 +C15337,3U01HL142109-04S3,Enhancing patient and organizational readiness for cardiovascular risk reduction among ethnic minority patients living with HIV,"Project Summary/Abstract In response to NOT-OD-21-020, Notice of Special Interest: Administrative Supplement for Research and Capacity Building Efforts Related to Bioethical Issues, this innovative proposal aims to conduct bioethical research to promote equitable COVID-19 vaccine decision-making among Black and Latinx people living with HIV (PLWHIV) and cardiovascular (CVD) risk. To mitigate the disproportionate impact of COVIID-19 on communities of color, COVID-19 vaccines must quickly reach those in greatest need. However, vaccine hesitancy and lack of access to reliable COVID-19 information compromise informed decision-making, reducing equitable and fair access to COVID-19 vaccines and inhibiting vaccine uptake in vulnerable subpopulations. This proposal seeks to expand the reach of public health messages (e.g., The COVID-19 Vaccine Education Initiative Public Health Toolkit and The Community Engagement Alliance (CEAL) against COVID-19),with an interactive session that acknowledges COVID-19 vaccine concerns, supports discussion of sources of hesitancy, and facilitates equitable access to reliable information within the context of multiple values (e.g., personal, bodily, communal) that impact COVID-19 vaccine decision-making. The Specific Aims are to: 1) evaluate the effect of a virtual session on knowledge of, access to, and trust in reliable COVID-19 public health messages among 60 HHMB participants (20 Spanish) living with HIV and at risk for CVD, 2) identify COVID-19 vaccine concerns specifically related to HIV and CVD risks, 3) determine the impact of the virtual session on HHMB participants' perception that they have adequate information to make a COVID-19 vaccine decision, making a COVID-19 decision, and whether or not the decision is to receive a COVID- 19 vaccine, and 4) evaluate the relationship between use of personal, bodily, and communal values taught in the virtual session, making a COVID-19 decision, and deciding whether or not to receive a COVID-19 vaccine. These aims will be addressed through a novel, culturally consistent session, ""Promoting COVID-19 Vaccine Decision-Making (HHMB-PVDM) for enrolled virtual HHMB participants. Without the opportunity to engage in dialogue about personal and historical experiences that impact hesitancy and provide support for increasing knowledge of and access to accurate, clear, and understandable COVID-19 public health and vaccine information, Black and Latinx PLWHIV and CVD risks will continue to lack equity in making COVID-19 vaccine decisions. Supporting COVID-19 vaccine decision-making approaches will facilitate population-level vaccine uptake, contributing to the mitigation of disparities in COVID-19 morbidity and mortality in communities of color. Findings will be refined to inform vaccine decision-making approaches to reach other vulnerable subpopulations.",2021,2022,N/A,156000,Human Populations,Black | Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2018 +C15338,1R21NS123871-01,Neurological consequences of COVID-19 during the early recovery period: Imaging Analysis of the Blood Brain Barrier and Neurovascular alterations,"This investigation will use state-of-the-art, quantitative Magnetic Resonance Imaging to determine whether SARS-CoV-2 has effects on the brain that can be detected at one month and at 6 months following mild to moderate COVID. Blood brain barrier integrity, cerebral blood flow, cerebrovascular injury, subclinical structural alterations, brain network organization and cognitive function will be evaluated. The findings will shed light on whether COVID confers increased risk of neurovascular pathophysiologic changes and cerebral small vessel disease. This investigation will determine whether brain alterations detected in the early recovery period relate to known risk factors for COVID severity and to immune perturbances during the active phase of illness. A comprehensive analysis of the brain in the early recovery period will yield critical insights concerning the natural history of SARS-CoV-2 and the impact on the brain, and will provide a valuable cohort for further longitudinal studies of the neurological consequences of COVID.",2021,2023,N/A,439694,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15340,3U01HL146208-03S2,COVID-19 vaccine serologic immune response in people with HIV,"TITLE: COVID-19 vaccine serologic immune response in people with HIV ABSTRACT MWCCS participants are a high-risk group for severe COVID-19 disease in terms of being HIV-infected, predominately of elderly age, and having numerous underlying comorbidities. Therefore, it is imperative that they receive the new COVID-19 vaccines. In Aim 1 we will study the kinetics and immunoglobulin subclasses of COVID-19 vaccine-induced antibody responses in MWCCS male and female people with HIV (PWH) and matched HIV-uninfected controls (HUC) in a 3-year, longitudinal study against a background of HIV infection and cardiovascular comorbidities. We will perform quantitative assays to study anti-S antibody binding, virus neutralization and the capacity of the antigen-specific IgG1, IgG3 and IgA to mediate complement activation. This will be examined via serological levels of C1q, C3, C3a and C5a. MWCCS core longitudinal visit sera will be analyzed to determine COVID-19 infection post-immunization by detecting anti-N antibodies and to quantify the effect of additional immunizations with COVID vaccines. We will also assay sera for soluble immunological pro- and anti-inflammatory and other biomarkers that relate to HIV-1 infection and cardiovascular disease (CVD) to assess the effect of COVID-19 vaccination on these systemic parameters. In Aim 2 we will analyze the multi-omic immune parameter datasets generated in this project to discover, design, and optimize immune responses against the COVID-19 vaccine in PWH. Our hypothesis is that immunological biomarkers that predict COVID-19 vaccine response outcomes are identified by machine learning approaches on the entire set of features quantified in Aim 1. We will identify innate and adaptive immune parameters from Aim 1 that serve as biomarkers of COVID-19 vaccine outcomes in MWCCS participants using machine learning. This includes assessment of plasma HIV virus load and biomarkers of HIV-related immune activation and inflammation associated with chronic cardiovascular disease parameters already documented in MWCCS participants. This study will be a platform for further, targeted use of core samples for an in-depth investigation of vaccine- mediated immune mechanisms of protection. The participants who seroconvert, defined as V101 anti-N negative followed by anti-N positive sample, will be targeted for in-depth investigation of the immune mechanisms of vaccine-mediated protection, the immunologic responses and virologic characteristics of breakthrough SARS-CoV-2 infections in future investigations.",2021,2026,N/A,751032,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2019 +C15341,3R25GM129875-04S1,Addressing vaccine hesitancy in Baltimore City through a youth engagement/health literacy STEM initiative,"Project Summary/Abstract University of Maryland (UMB) CURE Connections (C2) is an integral component of a minority STEM education pipeline in which West Baltimore high school students gain STEM enrichment including hands-on research and community outreach through a network of minority-focused college programs at UMB and its partner institutions. For this project, we will expand upon our current C2 curriculum by adapting, implementing, and evaluating a youth-engagement/health literacy strategy to address COVID-19 vaccine hesitancy and increase vaccine uptake. Central to our aims is a new capacity-building partnership with the University of Maryland Center for Vaccine Development (CVD), a nationally recognized leader in vaccine research that has been at the forefront of COVID-19 vaccine development and testing. We will integrate CVD expertise and resources into our established network of community, medical center, and local government sectors partners. CVD partners will support the adaptation of the Wellness Champions for Change-Student (WCC-S) curriculum to address COVID- 19, vaccine science, and promotion of vaccine uptake. This curriculum originally focused on obesity prevention and was developed and tested at UMB as a model for health promotion via youth advocacy/health literacy. This new vaccine-focused curriculum will be implemented during our 6-week intensive summer programming with C2 high school scholars. C2 scholars will then work with CVD faculty/students and UMB community partners to disseminate vaccine education in West Baltimore communities. In this proposal, we will use the adaptation framework, FRAME, to develop modifications to the curriculum to focus on vaccine hesitancy and access. Specifically, we aim to: (1) Adapt a youth advocacy/health literacy curriculum originally developed for obesity prevention using the FRAME adaptation framework to tailor content to address vaccine hesitancy as a strategy to increase COVID-19 vaccine uptake among West Baltimore residents. This curriculum will align with Next Generation Science Standards to provide foundational knowledge required to understand and translate concepts related to vaccine science and teach skills focused on health literacy promotion, youth advocacy, and community engaged research that culminates with a scholar-driven community project to reduce vaccine hesitancy. (2) Implement and evaluate the adapted curricula with a cohort of C2 scholar high school students via a 6-week summer program. The C2 scholars are the cornerstone of this proposal and function as credible conduits for dissemination of vaccine education from UMB to the West Baltimore communities in which they reside. The success of this program will demonstrate the feasibility of cross-sector partnerships and their potential to help erode structural racism that is at the heart of vaccine hesitancy and access disparities. Program adaptations to address vaccine uptake provide a model for its application to address future public health issues thereby creating a sustainable, community-focused infrastructure for public health promotion.",2021,2023,University of Maryland,54000,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2018 +C15342,1R01AI158569-01,Advancing the development of a novel class of small molecules for treating pan-coronavirus infections,"Abstract For the past decade, our laboratory has been studying the role of cellular kinases in intracellular trafficking of RNA viruses and as targets for broad-spectrum antivirals. Furthermore, we have provided a proof of concept for the potential feasibility of the host-targeted broad-spectrum antiviral approach by demonstrating that the inhibition of two cellular kinases, AAK1 and GAK, by novel or the approved anticancer drugs, sunitinib and erlotinib, protects mice from dengue and Ebola viruses with a high barrier to resistance. Since the therapeutic index (TI) of this drug combination is narrower for SARS-CoV-2 infection, here, we focus on an independent class of compounds, the isothiazolo[4,3-b]pyridine-based RMC-113 series, that emerged from our prior work, but does not inhibit AAK1 or GAK. We showed that RMC-113 and 25 related analogs have potent broad- spectrum antiviral activity with a high barrier to resistance. Excitingly, RMC-113 reduces SARS-CoV-2 titer to undetectable levels at non-toxic concentrations and binds PIKFYVE, a cell kinase that regulates endosomal trafficking. We hypothesize that RMC-113 analogs inhibit both multiple distinct steps in the SARS-CoV-2 life cycle and the inflammatory response to this virus, in part by targeting PIKFYVE, thereby offering attractive and safe candidate inhibitors to combat SARS-CoV-2, other pandemic coronaviruses and other emerging viruses. In Aim 1, we will use a multi-dimensional medicinal chemistry approach to optimize the TI and PK profile of lead RMC-113 analogs and define their in vitro therapeutic potential as broad anticoronavirus inhibitors. Aim 2 will determine the effect of prioritized analogs and apilimod, a repurposed drug candidate for COVID-19 that inhibits PIKFYVE, on viral replication, cytokine response and tissue injury in organoids derived from excised normal lung tissue supplemented with PBMCs from 20 human donors and in two rodent models. Aim 3 will generate ADME-toxicity and safety pharmacology datasets to select pre-IND candidates. In Aim 4, we will probe the mechanism of antiviral action of RMC-113. We will validate PIKFYVE as a candidate target and use an unbiased CRISPRi screen to identify RMC-113's target(s) and profile its chemical-genetic landscape. In parallel, we will design a clickable RMC-113 probe to confirm the molecular target via activity-based protein profiling and to monitor target engagement. Lastly, we will probe functional relevance and specific roles of PIKFYVE and other candidates emerging via these approaches in SARS-CoV-2 infection, and validate them as the molecular target(s) mediating the antiviral effect. The predicted immediate impact is that this project will provide insight into the therapeutic potential and MOA of apilimod, a repurposed drug candidate (beyond the reported effect on viral entry), and will establish a unique human lung organoid model for studying SARS-CoV- 2 pathogenesis and response to treatment under more natural conditions. In the longer term, successful completion of our study will deliver a drug-like small molecule candidate designed to protect against resurge of COVID-19 and to provide readiness for future outbreaks with coronaviruses and other emerging viruses.",2021,2026,N/A,779425,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Disease pathogenesis | Pre-clinical studies | Prophylactic use of treatments,2021 +C15343,3U54MD007582-36S1,FAMU Center for Health Disparities Research,"SUMMARY The overall goal of this community partnership is to expose social determinants as well as behavioral, and ethical factors that may influence COVID-19 vaccination among racial, ethnic, and vulnerable community populations in Gadsden County, Florida. The County has among the country's highest shares of residents who are housed in nursing homes, prisons, or in other institutionalized group quarters (8.4%), and of households with no access to a vehicle (11.7%). Over the years, the College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health has developed strong collaborative relationships with community organizations in Gadsden County through various community-based participatory research projects. The study investigators have partnered with Gadsden County stakeholders and community-based organizations on several racial disparity issues such as infant mortality, cancer, diabetes, cardiovascular disease, and HIV/AIDS. As part of our community-based participatory approach, we will partner with the Gadsden Community Health Council to implement a quantitative survey to measure the perceptions of the community regarding the disparities in COVID-19 among racial/ethnic populations as well as intent to vaccinate against the virus. Additionally, qualitative interviews will be conducted with community members to better understand perceptions of vaccine hesitancy among vulnerable racial and ethnic populations. A behavioral intervention will be implemented utilizing CDC's Community-Based Organizations COVID-19 Vaccine Toolkit and The Toolkit for Community and Faith-Based Organizations. Pre and Post intention to vaccinate will be based on the Theory of Planned Behavior.",2021,2024,N/A,323255,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,1997 +C15344,3R25GM137169-02S1,VetaHumanz Need Vaccines Too!,"PROJECT SUMMARY/ABSTRACT T he parent grant, See Us-Be Us, responds to critical gaps in K-1 2 ST EM education, by increasing (1 ) v isibility of veterinary role models diverse in race and ethnicity, (2) access to veterinary STEM educational materials, and (3) access to experiential learning opportunities. Since the start of funding on September 1, 2020, the veterinary STEM ecosystem proposed in the parent grant has expanded beyond academia by transforming into a veterinary superhero league, The League of VetaHumanz. VetaHumanz are human beings (veterinarians) with superpowers who protect animal and public health. As a nation, we face the challenge of increasing vaccine acceptance by underserved populations who have been disproportionately impacted by SARS-CoV-2, lack access to healthcare, and have a longstanding mistrust of medical establishments resulting from a history abuse and exploitation. This administrative supplement, VetaHumanz Need Vaccines Too!, aims to promote SARS-CoV-2 vaccination uptake in underserved communities by educating children and their families on the importance of vaccination, empowering children to becoming advocates for vaccination, and inspiring children to explore veterinary careers that impact public health. Our focus on early elementary school children is innovative because we have an opportunity to educate underserved children who have not yet developed a long-term mistrust of our medical system. In the short term, children can positively impact the health of their communities by advocating for vaccination. In the long term, children can change the narrative by aspiring to become veterinary scientists that better represent the US population and are worthy of public trust. We hypothesize that after becoming informed about vaccines and the importance of SARS-CoV-2 vaccination, children will actively promote vaccination in their communities and aspire to become veterinarians. This supplement has three specific aims. T he focus of Aim 1 is to dev elop a Vaccine SuperPower Pack. Vaccine SuperPower Packs will contain educational materials for children about the importance of vaccines. Packs will also encourage pursuit of veterinary careers and communication of scientific knowledge by featuring the superhero veterinary scientist who hosts the VetaHumanz Live! podcast. Aim 2 is focused on promoting SARS- CoV-2 vaccination by featuring veterinarians who have been involved in the response to SARS-CoV-2 through the VetaHumanz Live! podcast which will be broadcast through our website and community events. Aim 3 promotes SARS-CoV-2 vaccination through a League of VetaHumanz social media campaign. Our League of VetaHumanz, a far-reaching, inclusive veterinary STEM ecosystem consisting of veterinary professionals, veterinary students, and community entities serving disadvantaged youth, will provide the frameworkfor distribution of educational resources and messaging. VetaHumanz will educate children as well as model being vaccinated for SARS-CoV-2 on social media campaigns, because even superheroes need vaccines.",2021,2025,N/A,54000,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2020 +C15345,3P20GM103429-20S1,Understanding Hesitant Adopters,"ABSTRACT COVID-19 has become one of the leading causes of death in the United States (US), and racial and ethnic minority groups experience higher risks of exposure, hospitalization, and death due to COVID-19. Population immunity through the uptake of a vaccine is critical to stopping the spread of COVID-19; however, racial and ethnic disparities in vaccine hesitancy raise concerns about whether vaccination programs will further widen COVID-19 disparities. Minority populations have reported greater hesitancy to get the COVID-19 vaccine, with some communities of color half as likely to get the COVID-19 vaccine compared to Whites. To reduce disparities in COVID-19-related morbidity and mortality, we must understand and address racial disparities in vaccine behavior. The proposed study will utilize a mixed-methods nested-study approach including two steps of data collection. Data will be collected using random digit dialing to conduct a cell and landline phone survey of adult Arkansans (N=1800). Then, we will utilize a purposeful/random sample (N=50) drawn from the phone survey participants who are hesitant adopters (i.e., expressing both hesitancy and having received the COVID- 19 vaccination) for qualitative data collection. The purposeful sample for the qualitative portion will provide rich qualitative data on hesitant adopters. Both sampling methods will oversample Black/African American and Hispanic/Latino participants. Our specific aims are: Aim 1. Examine characteristics associated with vaccine hesitancy/willingness and vaccine behavior (e.g., vaccinated or not) between and within racial/ethnic groups using quantitative methods (random sample of N=1800) informed by the Increasing Vaccination Model. Aim 2. Examine the characteristics that distinguish hesitant adopters from hesitant non-adopters using quantitative methods (random sample of N=1800) informed by the Increasing Vaccination Model. Aim 3. Examine the role of thoughts and feelings, social processes, motivations and practical issues in the process of becoming compliant among those who are hesitant and get vaccinated using qualitative methods (purposeful random sample N= 50) in a nested design informed by the Increasing Vaccination Model. Although there is much research documenting the problem of vaccine hesitancy and differences in hesitancy based on race and ethnicity, almost no studies provide information about what might be done about it. Examining those who are hesitant but are vaccinated is key to better understanding factors which might increase uptake despite hesitancy. This study will provide new and actionable information that researchers and healthcare providers can use to create interventions to increase vaccination uptake among the hesitant.",2021,2025,N/A,253334,Human Populations,Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2001 +C15346,75N93021C00054-0-9999-1,Discovery of Isotucaresol derivatives as adjuvants for vaccines testing in a SARS-CoV-2 vaccine model,"The long-term goal of the program is the commercial development of synthetic mimetics of novel saponin adjuvants that can be produces as single chemical entities on a large scale, are chemically more stable than current saponin adjuvants.",2021,2023,N/A,598808,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Vaccine design and administration,2021 +C15347,1R43AI165016-01,Novel antibody polymer reagents for SARS-CoV-2 detection,"PROJECT SUMMARY There is an urgent need to rapidly detect SARS-CoV-2 (CoV-2) virus in clinical and nonclinical settings, including point of care sites, workplace, and home, at sensitivity and specificity comparable or superior to RT-PCR detection of CoV-2 RNA. Much of the person-to-person CoV-2 transmission occurs before infected individuals develop symptoms. This significant pre-symptomatic/asymptomatic reservoir of CoV-2 transmission mandates efficient identification of infected individuals and their contacts at population-wide screening scale to prevent outbreaks of Covid-19 disease while allowing societies to open and economies to recover. This level of surveillance will also be needed to fully evaluate the effectiveness of countermeasures, including vaccines and therapies. We will develop a new class of diagnostic product reagents, antibody polymers, to create products that can be produced and used at population screening scale for rapid CoV-2 antigen detection at significantly improved sensitivity that approaches the sensitivity of :gold-standard"" RT-PCR detection of CoV-2 genomic RNA. Our antibody polymers will be produced by engineering a novel class of small, stable, single polypeptide anti- CoV-2 antibodies termed variable lymphocyte receptors (VLRs) as polymers to achieve essentially irreversible binding to CoV-2 virus. VLR polymers are compatible with all diagnostic immunoassay forms, including lateral flow assay (LFA) ""dipsticks"", which is likely to be preferred in non-laboratory settings, and with established signaling modalities, e.g., colloidal gold and horseradish peroxidase (HRP). VLRs, the antigen receptors of jawless vertebrates (lamprey and hagfish), are composed of highly diverse leucine-rich repeat domains and are the only known antigen-specific immune receptors that are not immunoglobulins (Igs). The binding site of VLRs is contained within a small single polypeptide and comprised by amino acid residues in the rigid beta-sheets that form the concave surface of the VLR structure. The over 500 million year evolutionary separation of jawed and jawless vertebrates and distinctive antigen-binding site structure of VLR antibodies have proved a source of novel specificities distinct from conventional Ig antibodies. The outer envelope of the CoV-2 virus is composed of a multivalent array of spike (S) protein that is an ideal target(s) for multivalent, essentially irreversible binding, by appropriately multivalent binding agents. We will genetically link in tandem genes encoding VLRs with binding specificity for CoV-2 S protein to create such multivalent VLR polymer binding agents that couple binding of CoV- 2 antigens to an amplifiable, visually observable result, e.g., color change. The high ratio of CoV-2 S protein 50 - 100 S protein trimers per virus particle, to the single copy CoV-2 RNA genome, and the amplification available via catalysis, e.g., HRP, provides significantly improved CoV-2 antigen detection sensitivity that approaches sensitivity achieved with RT-PCR detection of single copy CoV-2 RNA.",2021,2022,N/A,256506,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15348,3UM1AI148575-02S8,Vaccine and Treatment Evaluation Units (VTEU)-DMID 21-0004,"BAYLOR COLLEGE OF MEDICINE- ABSTRACT The purpose of this study is to evaluate the immunogenicity and safety of various licensed or EUA SARS-CoV-2 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in infants. We will also evaluate the durability of the antibodies in mothers and infants and assess breast milk antibodies in lactating women. We will evaluate breast milk antibodies to assess potential for protection against COVID- 19 in breastfed infants, similar to influenza vaccine protection from influenza illness in infants of mothers vaccinated during pregnancy or postpartum. We anticipate including up to 5 vaccines as part of this non-interventional study. It is expected that the results of this study will inform policy recommendations and personal decision-making on the use of approved SARS-CoV-2 vaccines in pregnant and lactating individuals.",2021,2024,BAYLOR COLLEGE OF MEDICINE,308091,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Vaccines research, development and implementation",Phase 2 clinical trial | Characterisation of vaccine-induced immunity,2021 +C15349,1R01MD016744-01,Leveraging community health workers to improve SARS-CoV-2 testing and mitigation among criminal justice-involved individuals accessing a corrections-focused community-based organization,"Abstract. The United States (U.S.) has experienced higher mortality than any other nation due to COVID-19 with nearly 13.5 million cases and over 268,103 deaths. Due to the limited ability to socially distance, poor ventilation, and limited hygiene supplies, U.S. prisons and jails have observed explosive transmission of SARS-CoV-2 accounting for the 10 largest U.S. outbreaks. Because 95% of criminal justice-involved individuals reenter society COVID-19 transmission extends beyond those who are currently incarcerated. As justice-involved individuals reenter the community, they face high rates of homelessness, and many others live in other congregate settings such as converted hotels and halfway houses. The increased risk of SARS-CoV-2 while incarcerated coupled with the likelihood of living in congregate settings after incarceration, create conditions ripe for rapid COVID-19 transmission that will be critical to address in order to gain control of COVID-19 in the U.S. The goal of this study is to test the impact and cost-effectiveness of an intervention to mitigate SARS-CoV-2 transmission among justice-involved individuals recently released from incarceration. We will conduct a randomized trial to compare the effectiveness of an onsite Point-of-Care SARS-CoV-2 testing and education intervention with community health workers (CHWs) as a central component compared to the standard of care at a community-based organization (CBO) that provides services to justice-involved individuals in New York City. We will measure costs of testing, education, and navigation, and explore the cost-effectiveness of the onsite Point-of-Care intervention compared to the standard of care. Our specific aims are to: 1) Test the effectiveness of an onsite PoC SARS- CoV-2 intervention in a corrections-focused CBO; 2) Model the cost-effectiveness of an onsite PoC SARS-CoV- 2 intervention among CJIs compared to SoC. Because testing, education, and navigation will be provided by CHWs in a culturally-sensitive environment and test results will be received in minutes (rather than days), we hypothesize that O-PoC will be associated with improved testing uptake and receipt of test results, mitigation behaviors (mask wearing, hand hygiene, social distancing), and those who attend more O-PoC sessions will have better adherence to mitigation behaviors.",2021,2026,N/A,751585,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience","Diagnostics | Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions | Policy research and interventions",2021 +C15350,1R21EB031347-01,A muco-penetrating biomaterial-based subunit vaccine for programming protective immune responses to SARS-CoV-2,"1. ABSTRACT/SUMMARY Given that the site of entry of SARS-CoV-2 is the respiratory mucosa, an effective vaccine for SARS-CoV-2 should initiate both humoral and respiratory mucosal immune responses. Although an intranasal subunit vaccine would be an ideal platform for SARS-CoV-2, transport across the nasal mucosa and a lack of safe and effective mucosal vaccine adjuvants thwart the development of a clinically-viable intranasal subunit vaccine. We propose to develop an intranasal vaccine composed of SARS-CoV-2 proteins conjugated to an immunostimulatory biomaterial that overcomes the transport barriers of the nasal mucosa and thus induces protective mucosal and systemic immunity. Our platform is composed of SARS-CoV-2 receptor-binding domain portion (RBD) conjugated to water-soluble polymers, termed MPGAP, that are synthesized from monomers that bind nasal mucus, disrupt endothelial thigh junctions, and target and activate antigen presenting cells (APCs). Thus, when administered intranasally, RBD- MPGAP conjugates should (1) adhere to nasal mucus, increasing residency time at the nasal epithelium, (2) dismantle tight junctions, maximizing paracellular transport to underlying APCs and nasal associated lymphoid tissue, (3) target conjugated RBD to and activate APCs, eliciting APC-derived signals that activate T and B cells. By overcoming the biological barriers of the nasal endothelium and targeting immunostimulatory factors to immune cells, RBD- MPGAP should induce protective mucosal and systemic immunity in the absence of off-target effects. RBD-MPGAP conjugates will be produced, characterized, and their ability to bind nasal mucus, enhance paracellular transport, and target and activate antigen presenting cells will be tested in mice. The neutralizing antibody titer of serum and respiratory fluids from RBD-MPGAP-immunized mice will be assessed via an in-vitro SARS-CoV-2 neutralization assay. Finally, the protective efficacy and durability of the mucosal and systemic immunity elicited by internasal RBD-MPGAP will be investigated in a SARS-CoV-2 mouse model. Completion of this project will validate the preclinical efficacy of an intranasal SARS-CoV-2 subunit vaccine and deliver a platform that could combat numerous other respiratory infections, from seasonal influenza to the next respiratory viral pandemic.",2021,2024,N/A,204688,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C15351,3R01AI138709-04S1,Comprehensive profiling of SARS-CoV-2 antibody responses and escape pathways,"The ongoing global pandemic of the novel SARS-CoV-2 coronavirus (CoV) presents an urgent need for development of effective preventative and treatment therapies. The viral-host cell fusion (S) protein spike is a prime target for such therapies owing to its critical role in the virus lifecycle. The S protein is divided into two regions: the N-terminal S1 domain that caps the C-terminal S2 fusion domain. Binding to host receptor via the Receptor Binding Domain (RBD) in S1 is followed by proteolytic cleavage of the spike by host proteases. This leads dramatic conformational transitions resulting in S1 shedding and exposure of the fusion machinery in S2, culminating in host-cell entry. Class I fusion proteins such as the CoV S protein that undergo large conformational changes during the fusion process must, by necessity, be highly flexible and dynamic. Indeed, cryo-EM structures of the SARS-CoV-2 spike reveal considerable flexibility and dynamics in the S1 domain, especially around the RBD that exhibits two discrete conformational states - a ""down"" state that is shielded from receptor binding, and an ""up"" state that is receptor-accessible. The overall goals of this study are to use our robust, high-throughput computational and experimental pipeline to define the detailed trajectory of the ""down"" to ""up"" transition of the SARS-CoV-2 S protein, identify early metastable intermediates in the fusion pathway, and exploit their structures and dynamics for identifying drug and vaccine candidates that target SARS-CoV-2. A wealth of structural information on CoV spike proteins, including recently determined cryo-EM structures of the SARS-CoV-2 spike, provides a rich source of detailed data from which to begin precise examination of macromolecular transitions underlying triggering of this fusion machine. The scientific premise of this study is that understanding the structural dynamics and early transition kinetics of mobile regions of the SARS-CoV-2 spike will allow optimal control of vaccine and drug responses, and facilitate the development of novel antiviral drugs and protective vaccines. At the culmination of this study, we expect to have determined structures of multiple ""down"", ""up"", and intermediate states of the SARS-CoV-2 S protein. Together, these studies will provide important atomically detailed structural and mechanistic information for exploitation in vaccine and therapeutics design.",2021,2023,N/A,489662,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C15352,75N93020C00053-P00001-9999-1,Development of a COVID-19 Vaccine,"To support the advanced development of candidate products for use following the intentional release of or in response to naturally occurring outbreaks of infectious diseases caused by NIAID Category A, B, and C Priority Pathogens or emerging infectious diseases. This contract may support formulation and manufacture of the individual vaccine components, as well as stability testing, nonclinical immunogenicity and efficacy testing in animal models, IND enabling GLP toxicology, submission of an IND and clinical safety and efficacy evaluation.",2020,2022,N/A,1549907,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus | Novel Pathogen | Unspecified,,,,,,,,,COVID-19 | Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",,2020 +C15353,3R24AG063718-03S1,COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS) II,"Project Abstract/Summary of COMPASS The COVID-19 pandemic has continued to have devastating health, social, and economic implications in the U.S. COVID-19 has intensified the significant health disparities, socio- economic inequalities, and discrimination/xenophobia that exist, both prior to and due to COVID-19. COVID-19 related policies (e.g., shelter-in-place; social distancing) have placed vulnerable populations including racial/ethnic minorities as well as those who are low-income, have limited English proficiency, and are socially and technologically isolated in even more dire situations and risk for poorer health. Asian Americans and Pacific Islanders (AAPI), in particular, encompass all of these aforementioned characteristics. AAPI also experience significant health disparities, which has likely been exacerbated due to COVID-19, and reports of discrimination and xenophobia in the AAPI population due to COVID-19 are alarming. Older AAPI, especially, are more likely to be disproportionately affected by COVID-19 policies. Also, persons with health conditions such as cognitive impairment (i.e., Alzheimer's disease and related dementias [ADRD]) may forget to perform precautions to prevent COVID-19 (e.g., handwashing). Caregivers' health may also be affected (e.g., less respite options; more care management responsibilities; fear/anxiety of infection for self and care recipients, economic instability). The goal of this proposed research, COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS) II, is to assess the longitudinal effects of COVID-19 on AAPI from COMPASS I, the largest COVID-19 national study of AAPI to date (N=5,242). COMPASS leveraged the only AAPI registry in the U.S., Collaborative Approach for AAPI Research and Education (CARE) in ADRD, aging and caregiver-related research, to achieve this goal. Through our strong academic-community partnerships, we will conduct a follow-up with COMPASS I participants to complete a multilingual follow-up survey about the impact of COVID-19 on their health, healthcare access, caregiving, experience with discrimination, employment, and income. We will also examine pre- and post-differences in COVID-19 vaccine willingness and concerns (pre-/post-availability of FDA-approved vaccines), and whether such differences are associated with the receipt of the COVID-19 vaccine. COMPASS participants will complete a multilingual follow-up survey about their health (physical, mental and financial), changes in receiving healthcare and in caregiving, experience with discrimination/xenophobia, and, productivity. COMPASS II is both a necessary and natural extension of COMPASS I, and will help to inform future policies, programs and additional research that can alleviate the adverse effects of COVID-19 for AAPI.",2021,2022,N/A,464531,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2019 +C15354,3R01AA025603-04S1,Preventing Alcohol Exposed Pregnancy among Urban Native Young Women During the COVID-19 Pandemic,"The devastating impact of COVID-19 on American Indian and Alaska Native (AIAN) communities has been well-documented, with substantial focus on reservation communities, often rural and remote. However, more than 72% of AIANs reside in urban settings, a majority of the racial group, but a small fraction - often less than 1% - of most urban communities. Many urban AIANs are tightly connected to tribal communities and cultural practices, commonly traveling between urban areas and reservations to participate in family events or important cultural celebrations and ceremonies. However, this group is likely to experience different cultural, social, and economic impacts of the pandemic compared to those living in reservation settings. Those differences are likely critical to alcohol-exposed pregnancy (AEP) risk. Early data in the general population indicate increased alcohol use by youth, and decreased access to effective contraception among women. The combination is likely to increase risk of AEP, and for urban AIAN young women - often with limited local resources - that risk may be especially elevated. Yet, as research efforts scramble to monitor risk of the most vulnerable in a pandemic, this demographic often becomes invisible. We know little about the impact of COVID-19, the changes in alcohol use, sexual activity, or contraceptive use to assess risk among urban AIANs. Similarly, we know little about the way in which these young women are able to find resilience and strength in their communities to overcome the hardships presented by the pandemic or to engage in the promise of vaccines. Our project, Native WYSE CHOICES, uses a randomized trial to evaluate a culturally appropriate AEP prevention program translated to a smartphone app for urban AIAN young women (ages 16- 20) nationally. With our research infrastructure in place, we have the opportunity to tap shifts in behaviors, attitudes, and perceptions of urban AIAN young women, their families, and communities as they navigate the changing dynamics of the pandemic. We will (1) include additional survey measures with a national sample of 700 to capture the evolving pandemic in four main areas: (a) COVID-19 disease, risk exposure, and safety; (b) social and economic impacts; (c) COVID-19 vaccine attitudes, experience, and status; and (d) cultural and historical trauma impacts. To contextualize these findings, we will (2) conduct in-depth interviews with participants purposively selected based on baseline survey responses. To maximize insights in the diversity of experience of the pandemic and gain timely, in-the-moment, insights, we will recruit and interview young women from our RCT sample (n=32) over 2 years. We will also interview selected participants (n=8) at regular intervals over 2 years to capture their experiences longitudinally as circumstances of the pandemic shift. With this qualitative design - i.e. cross-sectional insights complemented by a longitudinal view of urban AIAN young women's journey through the changing circumstances - we will be able to integrate our statistical findings within an agile interpretive frame.",2021,2023,N/A,75411,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Urban Population/Setting,Pregnant women,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts | Social impacts | Economic impacts,2018 +C15355,1R56AG074467-01,SARS-CoV-2 and Precursors of Alzheimer's Disease and Related Dementias: An Ultrahigh Field (7T) MRI Study in a Diverse Multinational Cohort,"SARS-CoV-2 virus displays neurotropism in some infected patients with reports of viral invasion, inflammation, meningoencephalitis, microvascular injury, stroke, delirium and delayed cognitive and psychiatric symptoms. It is unclear if there is any acceleration of neurodegenerative processes and increased risk of Alzheimer's disease and related dementias (ADRD). Race-, ethnic- minorities and men are known to have a higher risk of dying from COVID and may also have a greater susceptibility to long-term neuropsychiatric sequelae. Ultrahigh field (7T) MRI has increased sensitivity and spatial resolution, compared to 3T MRI and can detect small changes in cortical and white matter structure, integrity and connectivity, inflammation, iron deposition, hippocampal subfields, venular injury and the locus coeruleus. The 7T MRI COVID Consortium is an international collaboration across 5 sites to enroll a diverse, multi-ethnic cohort of 780 persons, aged 55-80. Of these 260 persons will have well-documented SARS-CoV-2 infection (cases) and 260 will be 'illness' controls with a clinically similar non-COVID illness (e.g. pneumonia). Cases and controls will include >25% Hispanic and >25% African-Americans. Both groups will be compared to 260 healthy controls with documented normal cognition and no hospitalization in preceding 2 years. Additional data will be drawn from 40 persons with autosomal dominant early-onset AD and 180 population controls, all imaged with the same 7T MRI protocol. All participants will undergo 2 annual 7T MRI scans and 4 detailed exams comprising neurological, cognitive and psychiatric assessments, smell, gait, blood biomarkers of neurodegeneration (p-tau181, NFL, GFAP, amyloid) and systemic inflammation (CRP, IL6, IL10, TNF-alpha, IL1R) and surveillance for incident MCI, ADRD dementia. These exams will occur at the time of each MRI, and at 36, 48 months post-illness. We propose the following specific aims: Aim 1: Detail the range of (Aim 1a) Early (6-12 months) brain pathology in COVID survivors (Aim 1b) assess if early changes improve, persist or worsen at a delayed 7T MRI (12-18 months) and (Aim 1c) Compare findings in COVID survivors to MRI in preclinical EOAD. Aim 2: Compare cross-sectional prevalence of pre-illness ADRD and vascular injury (VCID) and of cognitive, behavioral, mood and functional outcomes across 3 groups. Aim 3: Relate early and delayed 7T MRI measures to subsequent risk of MCI, dementia and cognitive and gait trajectories. Aim 4: Explore if race/ethnic-, sex- differences, blood biomarkers, genetics, or early SARS-CoV-2 'treatments' are effect-modifiers, mediators, or neither, of the associations noted in Aims 1-3. Investigators leading this grant are also members of other larger, less detailed COVID consortia permitting harmonized data analyses. Our study will permit a better biological understanding of mechanisms and modifiers of long-term neurological and psychiatric sequelae of COVID. It could also help illuminate the role of viral infections, inflammation and immune response in ADRD.",2021,2022,N/A,3529440,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2021 +C15356,1DP2GM146457-01,Alveolus as Incubator: Functional Genomic Dissection of the Host Response to SARS-CoV-2 Infection.,"PROJECT SUMMARY/ABSTRACT The host inflammatory response is a double-edged sword that must vigorously defend against pathogens, but also requires restraint to prevent unintended injury to the host. The Cytokine Storm Syndrome (CSS) represents a state of unbridled inflammation that can be triggered by infections, including Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2). While evidence for dysregulated cytokine responses exists for the SARS-CoV-2-associated CSS (S-CSS), the precise cell types and viral factors that precipitate this response remain incompletely understood. Autophagy is a cytosol-to-lysosome degradative pathway that has important functions in host immunity. We have recently shown that autophagy genes in myeloid cells, preliminarily alveolar macrophages (aMΦ), confer protection in a murine model of CSS induced by intravenous TNF. We hypothesize that host autophagy may also have a pleiotropic role in limiting the S-CSS. We are motivated in this hypothesis since coronaviruses (CoVs) manipulate host autophagy-associated membranes for their own replication via the nonstructural protein 6 (nsp6). This proposal for the NIH Director's New Innovator Award will test the role of host autophagy and a viral antagonist in the triggering of S-CSS using both established and innovative methods. The project will utilize a model for SARS-CoV-2 infection in which the human ACE2 receptor (encoded by hAce2) is delivered to mouse lungs via adenovirus (AdV) vector. Additionally, we will determine the role of aMΦ-specific host pathways by utilizing mice deficient for GM-CSF signaling and devoid of aMΦ (Csf2rb-/-), that are durably restored with aMΦ by a single intranasal instillation of progenitor cells in neonates. The role of SARS-CoV-2 nsp6 in viral pathogenesis will be determined with recombinant viruses deleted for this factor or with naturally occurring point mutations hypothesized to facilitate infection. Moreover, we will develop an AdV-hAce2 vector system expressing sgRNAs to edit genes directly in susceptible respiratory cells in Cas9-transgenic recipient mice. We will generate pooled AdV sgRNA libraries via this method for in vivo screening approaches that may identify host pathways important for regulating infection not otherwise recapitulated by in vitro approaches. Further, we will reconstitute Csf2rb-/- mice with aMΦ cell progenitors containing pooled CRISPR libraries to identify host genes important for not only the aMΦ response to SARS- CoV-2 but also for fundamental aspects of aMΦ niche development. These studies have the potential to identify new areas for the development of host- and viral-directed therapies (e.g., the autophagy pathway and nsp6, respectively). The robust and versatile in vivo platforms established for functional genomic studies of a tissue site critical for the proximal response to SARS-CoV-2 have broader implications for the study of complex cell populations in diverse biological processes.",2021,2024,N/A,1410500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +C15357,1R21AI162594-01,Surveillance of wildlife and livestock for novel and emerging coronaviruses,"Project Summary There is an urgent need for coronavirus (CoV) surveillance in both wildlife and livestock. As seen repeatedly, CoVs have a propensity to jump species from their bat, rodent and avian reservoirs, often to intermediate species including livestock, before infecting humans. Our knowledge of North American CoVs in wildlife species is sparse and routine sequencing of livestock CoVs are limited. In our first aim, to detect and sequence coronaviruses in wildlife and livestock, we will utilize a pan-coronavirus RT-PCR to screen a unique sample set consisting of bats and wildlife rarely surveilled. The sample set is comprised of ~500 animals submitted to our veterinary diagnostic laboratory for rabies testing over a 12-month period and consists of pooled lung, spleen and intestine tissue homogenate. In parallel, we will screen food animal diagnostic submissions from animals with acute enteric and respiratory disease. Our second aim, to further characterize coronavirus genomes and characterize virus isolates, phylogenetic and recombination analysis will be performed with the assembled CoV genomes. Specifically, assembled genomes will be annotated and submitted to Genbank and made publicly available immediately. Phylogenetic analysis will determine if SARS-CoV-2, CoVs similar to SARS-CoV-2 or novel CoVs have emerged in non-human species. Recombination analysis will next be performed using SARS-CoV-2 and the assembled CoV genomes to determine if SARS-CoV-2 or related CoVs have undergone natural recombination and contributed genetic material to endemic CoV. Another component of this aim is to isolate and propagate the detected CoVs in cell culture. This latter aim is critical for further pathogenesis studies in the natural host and model organisms. This R21 exploratory project meets an urgent need for CoV surveillance at the human-animal interface, both in wildlife and livestock. Results from this study will identify emerging disease threats and develop critical tools, including sequences, detection methodology and cell culture adapted viruses that will enable further studies on possible zoonosis and enable preemptive action.",2021,2023,N/A,222750,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2021 +C15358,1R01DK128012-01A1,Extracorporeal SuPAR Extraction to Prevent COVID-19-associated Acute Kidney Injury,"Abstract Acute kidney injury (AKI) is a global problem that affects one in five hospitalized adults worldwide. It has a major impact on morbidity and healthcare utilization, with small changes in kidney function shown to be associated with both short and long-term complications. AKI is a characteristic feature of the disease caused by the SARS-CoV-2 virus, coronavirus disease 19 (COVID-19), with close to 50% of hospitalized patients developing acute kidney injury (AKI) and 20% of patients requiring dialysis. The pathophysiology of AKI is complex and dependent on both intrinsic factors (age, co-morbid diabetes, hypertension, pre-existing kidney disease) and extrinsic factors (nephrotoxic drugs, hypovolemia, intra-arterial contrast, infections). Inflammation is an under-explored but crucial link between intrinsic and extrinsic factors in the pathogenesis of AKI. We have identified soluble urokinase plasminogen activator receptor (suPAR) as an immune-derived mediator of kidney injury. The expression of suPAR by immune cells is heavily induced by various stimuli, notably RNA viruses such as SARS-CoV-2. High levels of suPAR in circulation are strongly predictive of kidney dysfunction, with prolonged exposure directly affecting the kidneys by pathologic activation of αvβ3 integrins expressed on podocytes, resulting in activation of GTPase, podocyte effacement and subsequent proteinuria. We have recently shown high suPAR levels predisposes patients to AKI in various clinical scenarios including the critically ill, likely by modulating mitochondrial respiration and inducing reactive oxygen species generation in proximal tubular cells, sensitizing them to additional insults. Most importantly, effects of suPAR on the kidneys were abrogated using anti-suPAR in experimental models, suggesting suPAR is a promising therapeutic target to mitigate AKI. We have found that suPAR is dramatically elevated in COVID-19 and independently predictive of AKI. Despite the significant burden of AKI overall and specifically in COVID-19, there has been little progress in the prevention and treatment of AKI. We hypothesize that suPAR extraction early in the hospitalization of patients with COVID-19 may decrease the risk of moderate to severe AKI. To that end we have planned a phase 1 clinical trial randomizing adult patients hospitalized for COVID-19 who have high suPAR levels to daily extracorporeal extraction of suPAR by apheresis using a suPAR-specific adsorber, or sham treatment for a total of 5 days. The primary outcome of the trial is the occurrence of treatment-related serious adverse events. Exploratory outcomes include the incidence of AKI, respiratory failure, and in-hospital mortality. We will assess the kinetics of suPAR extraction by measuring daily levels prior to and post-treatment, in addition to its impact on markers of inflammation and kidney function. The proposed work is innovative in that it is the first trial targeting an immune-derived factor for preventing kidney injury. In addition to advancing our understanding of the immune system as a mediator of kidney injury, this trial will clarify suPAR's role as a pathogenic factor, with major implications for the treatment of kidney disease beyond COVID-19.",2021,2024,N/A,326710,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Innovation,,,,United States of America,Clinical characterisation and management,Disease pathogenesis | Clinical trials for disease management,2021 +C15359,3R01AG069858-02S1,Regulation of eicosanoid signaling lipids to improve skeletal muscle function and increase healthspan during aging,"ABSTRACT COVID-19 symptom severity is directly linked to age as well as other comorbidities such as diabetes, poor respiratory function, and cardiovascular disease. As of September 22, approximately 7.0 million cases of COVID- 19 have been reported in the US, and the overall cumulative COVID-19 hospitalization rate is high, with individuals over age 65 twelve times as likely as those under 40 to be hospitalized for COVID-19. While in the hospital, many COVID-19 patients require respiratory support from a ventilator. Although many patients survive COVID-19, recovery is prolonged due to diaphragm muscle weakness and some never completely recover due to ventilator-induced diaphragm dysfunction (VIDD), a condition that reduces the ability of a patient to be weaned to independent breathing. VIDD risk and severity increase in elderly COVID-19 patients who are particularly susceptible because they spend weeks, as opposed to days, immobilized and on mechanical ventilation. There is currently no treatment for VIDD. This project proposes to acquire preclinical data in support of a therapy for VIDD that utilizes a promising new small molecule that acts by a mechanism different from previously tested therapeutics developed to treat VIDD. Our preliminary data suggest that Prostaglandin E2 (PGE2), the target of our drug, acts on both muscle stem cells (MuSCs) to augment their proliferation and regenerative function, and on mature myofibers to improve strength, particularly in the elderly. We hypothesize that PGE2/EP4 signaling will act in aged diaphragm muscles as in aged limb muscles and can be modulated to improve diaphragm muscle function. Specifically, we aim to (i) demonstrate that PGE2 augments the proliferative and regenerative function of MuSCs isolated from human diaphragm biopsies obtained 4 hr after patients are put on a ventilator and (ii) assess the efficacy of our drug in enhancing MuSC function and promoting myofiber hypertrophy to counter diaphragm atrophy in a rodent model of VIDD. Toward these goals, we will utilize human diaphragm biopsies obtained from young (< 40yr) and elderly (> 65yr) patients at the time of cardiothoracic surgery and perform both functional assays of PGE2 treated human MuSC regenerative capacity in culture and following transplantation into immunodeficient mice. We will also assess in human diaphragm if the rapid atrophy induced by a ventilator leads to a decline in PGE2 levels and disruption of TGF-beta, cAMP/CREB, and AKT/FOXO signaling pathways. Finally, we will determine if PGE2 elevation via our therapeutic improves diaphragm function and regenerative capacity in the context of mechanical ventilation in a well-established rodent model of VIDD, which causes diaphragm atrophy and reduced contractile force. The project is a preclinical collaboration between Stanford faculty, Dr. Helen Blau, who characterized a novel small molecule drug as a potential therapeutic for sarcopenia, and Dr. Joseph Shrager, a prominent cardiothoracic surgeon who has carried out VIDD clinical trials. Our drug, if proven effective, may allow earlier weaning from ventilators of COVID-19 patients and significantly improve COVID-19 outcomes, particularly for elderly patients.",2021,2024,N/A,597186,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C15360,3U54GM104938-09S3,CATCH-UP Vaccines,"Project Summary/Abstract This proposal unites academic and community partners to solve a dire need for SARS-CoV-2 vaccine uptake in rural, underserved minority, and at-risk populations. Oklahoma has high COVID-19 incidence, high vaccine hesitancy, and signs of a slowing SARS-CoV-2 vaccine uptake. Oklahoma's cumulative incidence is higher in rural compared to urban counties. AI people have a higher incidence of COVID-19 compared to white populations in Oklahoma. Despite high incidence, as of April 2021, an estimated 54% of Oklahomans who have not yet been vaccinated reported unwillingness to receive the SARS-CoV-2 vaccine. Vaccine hesitancy was even greater in AI people (62%). The most commonly reported concerns are vaccine side effects and safety (30%). Despite early progress in disseminating vaccines in Oklahoma, all signs point to waning interest in receiving a vaccine, with many vaccine clinics unable to fill all available slots, particularly in tribal clinics and rural areas. Our proposal is an extension of the Oklahoma Shared Clinical Translational Resources (OSCTR) project CATCH-UP (Community-engaged Approaches to Testing in Community and Healthcare settings for Underserved Populations) in partnership with community organizations who work with underserved minority and rural populations. We will build on existing strengths and infrastructure to improve SARS-CoV-2 vaccine uptake in these highly susceptible populations. The goal of the project is to pilot interventions to improve awareness and uptake of COVID-19 vaccination. The project aims to work with CATCH-UP community events to implement interventions to improve vaccine uptake among Oklahoma's underserved populations. To do so, the proposed study employs a multiphase optimization strategy (MOST). The proposed study uses the preparation and optimization phases of the MOST framework across the following aims: 1) Identify SARS-CoV-2 vaccination barriers/facilitators and assess acceptability and feasibility of a suite of evidence-based vaccine intervention strategies among Oklahoma's rural, minority, and high-risk populations to inform a targeted multicomponent intervention; and 2) Develop and optimize a multicomponent intervention to improve SARS-CoV-2 vaccination among Oklahoman's seeking SARS-CoV-2 testing at CATCH-UP testing events. We will conduct a pilot of these interventions based on community input, which will be evaluated for inclusion in a future, full-scale implementation study.",2021,2023,N/A,262500,Human Populations,Other,Unspecified,Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2013 +C15361,3R35NS097273-05S1,Expanding insights into FTD disease mechanisms,"ABSTRACT Up to two thirds of hospitalized COVID-19 patients show neurologic signs and symptoms. For example, some patients with COVID-19 experience cognitive changes (or brain fog) or suffer strokes and seizures. It is hypothesized that COVID-19-induced brain inflammation and white matter damage underpin the neurological manifestations experienced by patients with COVID-19. Since neuroinflammation and white matter damage are also implicated in Alzheimer's disease related dementias (ADRDs), COVID-19 may increase the risk of developing an ADRD. Nevertheless, many questions remain answered, and the subacute and long-term neurological effects of COVID-19 are unknown. We thus propose to undertake a comprehensive longitudinal study of patients with COVID-19 requiring hospitalization. To identify patients at risk of long-term neurological complications and warranting follow-up visits, levels of serum neurofilament light chain (NFL), a marker of neuron injury, will be measured in hospital. We based this on our recent findings that ~53% of an initial cohort of 142 hospitalized patients with COVID-19 had elevated serum NFL, and that higher NFL concentrations correlated with worse clinical outcomes, including the need for mechanical ventilation, intensive care unit admission, longer lengths of hospitalization and poor functional outcomes. As such, NFL measurements provide an efficient means to estimate the extent of neurological injury associated with the acute infection and pending systemic metabolic disturbances. We will follow consenting patients 3 months, 1 year and 2 years after discharge, and examine blood biomarkers of neuronal and astroglial injury, ADRD pathologies and neuroinflammation, imaging markers of neuroinflammation and Aβ deposition, and cognitive outcomes. These data will allow us to determine whether blood biomarker levels during hospitalization predict the emergence and severity of ADRD-related neurological signs and symptoms. We will also extend our prior neuropathological studies in patients with COVID-19 and ADRDs, and assess anoxic-ischemic cerebral white matter damage, neuroinflammation and microglial activation.",2021,2022,N/A,963625,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C15362,1R21AI159024-01A1,Obesity and COVID-19: Role of Adipose Tissue,"PROJECT SUMMARY/ABSTRACT Obesity is a major risk factor for severe outcomes in Covid-19, exceeding the risk associated with type 2 diabetes and hypertension by 3-fold. The underlying reason is unknown. While obese individuals may have an impaired immune response or a predilection towards inflammation, hypertension, and cardiac decompensation due to underlying metabolic syndrome, we hypothesize that a more specific mechanism is at play: ACE2, the receptor for the spike protein on SARS-CoV-2 is highly expressed in subcutaneous and visceral adipose tissue, which may allow for viral entry and replication. Particularly in peri-organ fat depots, inflammation, vasoconstriction and fibrosis as a consequence of viral infection and subsequent downregulation of ACE2 may contribute to organ damage including heart, gut, liver, and kidney. As such, the goal of this project is to determine whether SARS-CoV-2 infects human adipocytes from subcutaneous (SAT), visceral (VAT), epicardial (EAT), and paracardial adipose tissue (PAT), whether infection incites inflammation, and whether pharmacologic compounds that target the renin-angiotensin system (RAS)/ACE2 alter infectivity and inflammation. 1. Assess the ability of SARS-CoV-2 to infect adipocytes and/or other resident cells in adipose tissue (SAT, VAT, EAT, PAT) 2. Profile the inflammatory response in adipose tissue cells exposed to SARS-CoV-2 3. Determine the ability of pharmacologic compounds that target RAS/ACE2 to inhibit infectivity and/or inflammation The results of this research will: 1) address a fundamental and critically-important question: does adipose tissue play a role in the link between obesity and COVID-19, via increased infection and/or inflammation; and 2) evaluate the effects of treatments targeting RAS/ACE2 that may mitigate infectivity and/or inflammation in adipose tissue.",2021,2023,N/A,236175,Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2021 +C15363,1R21LM013638-01,Development of a vaccine informatics system and its application to identifying the impact of vaccine debate on immunization rates during a global pandemic,"Vaccine debate has been on social media for more than a decade, and a surge of anti-vaccine activities on social media has been detected during prior disease outbreaks. Nonetheless, how this debate changes and impacts the uptake rates for crucial vaccines during the COVID-19 pandemic remains unknown. The long-term goal is to counteract the negative impact of misinformation on digital platforms that threatens public health. The overall objectives of this application are to develop a publicly accessible vaccine informatics system to track vaccine debate, and to test the impact of vaccine debate on COVID-19 (if developed by 2021), flu, and HPV immunization rates during the onset of a global pandemic. The central hypothesis is that vaccine debate will increase and become more negative during the pandemic, leading to lower vaccine uptake rates. The rationale for this project is that discovering how vaccine debate changes and influences vaccine uptake rates during a pandemic will be critically important for managing and preventing disease spread. The central hypothesis will be tested by pursuing two specific aims: 1) Develop a vaccine informatics system to identify the frequency and valence of vaccine debate during and following the pandemic compared to the pre-pandemic baseline; and 2) Apply this system to identify the causal impact of vaccine debate on immunization rates during the pandemic. Under the first aim, ~1 million social media posts will be collected, and a deep-learning algorithm for classifying multimodal social media posts will be developed. This algorithm will address potential bias and noise in human annotations of vaccine debate that is increasingly politicized. The classification results will be tabulated in a Web portal so that daily and weekly statistics about pro- and anti-vaccine posts will be readily available. Under the second aim, a multimethod approach will be proposed that resolves the current barriers in research on vaccine refusal. This approach will use a survey of 2,000 individuals who represent the US population. The survey responses will be combined with the respondents' prior engagement with vaccine debate retrospectively collected from social media. These engagement data will be then classified by the machine- learning algorithm developed in Aim 1. This research is innovative because it proposes a robust co-teaching framework for addressing noisy human annotations of vaccine debate. It also proposes a statistical modeling technique that involves heterogenous metrics obtained from a multi-method approach for hypothesis testing. These innovations are timely and urgent as the current time presents a rare opportunity to identify the impact of vaccine debate on public health during the onset of a global pandemic. The feasibility of this proposed research is clear from the solid preliminary datasets collected from 2018-2020 that establish the pre-pandemic baseline. The proposed research is significant because it will produce a public barometer of vaccine debate and provide a methodological breakthrough in uncovering the reasoning behind refusing crucial vaccines during the global pandemic.",2021,2023,N/A,191420,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C15364,3R01HD098092-03S1,Intervening during the Prenatal Period with Women Exposed to Intimate Partner Violence to Improve Maternal Functioning and Infant Adjustment,"PROJECT SUMMARY Intimate partner violence (IPV) occurs at alarmingly high rates, with the highest risk of IPV exposure during pregnancy. IPV during this critical juncture is associated with postpartum depression, posttraumatic stress, disruption to the mother-infant relationship, and poor infant outcomes. There is also emerging evidence suggesting that the COVID-19 pandemic is exacerbating the prevalence of IPV. Paired with other, on-going pandemic-related stressors, women with a history of IPV, especially those in the perinatal period, may be particularly vulnerable to the negative ramifications of COVID-19. A critical need therefore exists for longitudinal research investigating the effects of the pandemic on IPV-exposed women and their young children. Given that the conditions of the pandemic fluctuate significantly across persons and time, intensive longitudinal methods that are able to capture dynamic change are likely to provide valuable insights into risk and resilience in these families. This urgent competitive revision seeks to address these pressing questions, leveraging the existing strengths of an ongoing NICHD-funded study of a theoretically-driven intervention program with pregnant, IPV-exposed women, the Pregnant Moms' Empowerment Program (PMEP; MPIs Miller-Graff & Howell, R01HD098092). The specific aims of the parent proposal are to (1) evaluate the efficacy of the PMEP for women's mental health, resilience and IPV victimization across the perinatal period, (2) evaluate the efficacy of the PMEP in promoting infant development and (3) test process models for treatment change for women and infants in the context of a two-site. The parent project includes assessments at 4 time points (2 prenatal, 3 months postpartum, 1 year postpartum). Currently (n=67) women of a targeted N=230 have enrolled in the parent project, and the project has fully adapted to telehealth delivery and assessments, allowing us to maintain excellent participant retention throughout the pandemic. The project proposed for the competitive revision will add monthly assessments of pandemic-related stressors and the collection of a 30-day daily diary on stress, mood, and mother-child relational quality immediately following the final assessment wave (i.e., 1 year postpartum), to address three unique and timely aims: (1) evaluating the indirect effects of intervention on pandemic-related stressors, (2) examining the moderating effect of social and instrumental supports, and (3) analyzing dynamic associations in daily maternal mood, perceived stress, and mother-child relational quality. Analyses will be conducted using multilevel and structural equation modeling. This project is innovative - not just in the context of the pandemic - but also in the field of IPV research more generally for its multi-time scale, multi-method design. Further, the specific aims address pressing questions relative to the social and behavioral impacts of COVID-19 on children and families, providing valuable information for the public health response that is informed by the needs of individuals most significantly affected by the pandemic.",2021,2024,N/A,138133,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Digital Health | Gender,,,,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2019 +C15365,1R41AI164999-01,Transient Gene Therapy as Broad Spectrum Antiviral,"Project Summary Currently there are very few antiviral drugs, and no broad-spectrum antiviral drugs. For example, Influenza A virus (IAV) causes 12,000-56,000 deaths and 150,000-750,000 hospitalizations annually in the US alone, despite the availability of vaccines and five FDA-approved drugs 1, 2. Resistance to two of the five existing drugs has already emerged 13. Second, SARS-CoV-2 a virus which causes COVID19 led to unprecedented death toll worldwide. Currently there are no anti-SARS-Cov-2 drugs that can target other corona viruses. Type I interferons (IFNs) are host cytokines providing protection against viral infections. There are several different layers of IFN negative regulation, and the ISG15/USP 18 host protein 4, 5, 6, 7 complex is responsible for suppressing the tail end of IFN inflammation. Human ISG15 knockouts have been identified and shown to control IAV and SARS-CoV-2 replication better than WT counterparts. Based on the evidence of efficacy and safety provided by these ISG15-deficient individuals, Lab11 Therapeutics is developing new drugs, transient host-mimicking modified mRNA therapies aimed at enhancing control of IAV and SARS-CoV-2 infection in the general population 4, 6, 7. Candidate drugs are recreating antiviral state identified and tested in the human system, but, for FDA approval, Lab11 Therapeutics must demonstrate safety and efficacy in an animal model, before proceeding with human in vivo studies. This STTR aims to test our modRNA cocktail drugs in animal models of IAV and SARS-CoV2 infection. The phase I hypothesis is that modRNA cocktail delivered intranasally will restrict IAV replication in mice and SARS- CoV-2 infection in hamsters. We will test this hypothesis in Specific Aim 1, by evaluating the effects of modRNAs on IAV in human and murine cell lines followed by in vivo testing in mice. In Specific Aim 2, we will evaluate the effects modRNAs have on SARS-CoV-2 in human and hamster cell lines followed by in vivo testing in hamsters. In Phase II, we propose to test different delivery modes and encapsulations of modRNAs to optimize the most effective delivery and antiviral protection. The global influenza market is valued at about 5 billion dollars, about a fifth of which relates to non-vaccine products. The patient population targeted by Lab11 Therapeutics will be hundreds of millions of individuals in the general population. Given the crucial role of IFN in the control of many viral infections (ISG15-deficient cells control have been shown to control the replication of 14 different viruses more effectively than WT cells), the lead drugs developed here for IAV and SARS-CoV2 are likely to be effective against other viral diseases too. This will provide Lab11 Therapeutics with opportunities for the licensing of different products with identical mechanisms of action on an indication-by-indication basis.",2021,2022,N/A,255932,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +C15366,3R01HD094380-04S1,Mechanisms of actions(s) of simvastatin in uterine leiomyoma,"PROJECT SUMMARY Regular menstruation is considered an indicator of whole-body health, and subtle changes in health can lead to noticeable fluctuations in the regular cycle. The large roll-out of COVID-19 vaccine was accompanied by anecdotal evidence that suggested that those who menstruate experienced changes in the menstrual cycle with some reporting unexpected spotting or heavier and/or longer cycles. Unfortunately, the initial clinical trials for the Pfizer, Moderna, and Johnson and Johnson vaccines did not follow up on possible menstrual cycle changes. The first aim of our project is to assess the clinical effects of the COVID-19 vaccination on the menstrual cycle using data from participants in our ongoing clinical trial who document their menstrual cycle using a menstrual diary. We will expand recruitment through a national, digital campaign: www.covidmenses.org. Data reported in the popular Period-Tracking App ""Clue"" will also be used to assess the clinical effects. The second aim will focus on the mechanisms of COVID-19 vaccines' effects on the menstrual cycle through assessing endometrial changes associated with vaccination. This will be done by comparing the immune cell profile at the level of the endometrium before and after vaccination as well as evaluating the expression of cytokines, chemokines and extracellular degradation mediators. The successful completion of this project will provide evidence on the effect of COVID-19 vaccination on menstrual health. This can reduce vaccine anxiety and hesitancy among those who menstruate.",2021,2023,N/A,300000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation",Adverse events associated with immunization,2018 +C15367,3U54GM115516-05S1,Overcoming Vaccine Hesitancy in Rural Northern New England for Adolescents and Adults,"Vaccinating a significant portion of the American population with the COVID-19 vaccines is critical to achieve herd immunity to end the pandemic. It was recently reported that 20% of rural residents will ""definitely not"" get vaccinated. Hesitancy is higher among rural Americans for reasons including perceptions about COVID-19 risk, personal and/or religious reservations, distrust of science and government, and misinformation about vaccinations. Across Vermont, Maine and New Hampshire, there is 25% less COVID-19 vaccination in our predominantly rural communities compared with the limited, more densely populated cities and towns. There is an immediate and compelling requirement to overcome vaccine hesitancy for two rural northern New England target populations. Our adult population is 34% fully vaccinated (as of 4/16/21). The adolescent population (13 to 18 years old) is 10% vaccinated with the first dose; rapidly inoculating this younger cohort is necessary to resume pre-pandemic in-school and structured extra-curricular life. We have a unique opportunity and responsibility to address vaccine hesitancy for both cohorts by two complementary strategies that will leverage the capabilities of the NNE-CTR. A community-engaged multidisciplinary approach, consistent with public health objectives, practices, and policies, will immediately impact COVID-19 incidence and accelerate progress toward mitigating the associated health, social and economic consequences. For the 13- to 18-year-old group, we will pursue a parental-informed peer-based social media ""influencer"" intervention based in a single rural Vermont county intended to increase recipient intention to get the COVID-19 vaccine (Specific Aim 1). Our hypothesis is that electronic word-of-mouth communication utilizing information dissemination through social media networks will promote peer persuasion to overcome vaccination hesitancy. For the 25- to 65-year-old group, we will pursue a shared decision making intervention (Specific Aim 2). Our hypothesis is that the shared and unique dimensions to communication between patients and physicians impacts receptiveness to COVID-19 immunization and overcoming vaccine hesitancy. To facilitate community engagement and maximize participation of rural northern New England primary care practices, program leadership and NNE-CTR infrastructure of the will partner with experts at the University of Vermont (UVM) and in the community. These include the UVM rural health communication researchers and practitioners, the Vermont, New Hampshire and Maine departments of health, the Northern New England Primary Care Practice-Based Research Network, the rural northern New England primary care consortium, and the liaison organization with northern New England schools, Vermont Afterschool Inc. Reducing rural inequities is a public health priority and the overarching commitment of this program. Our approach is nimble and scalable to respond to public health policies and practices, and required modifications in interactions in the immediate and foreseeable future.",2021,2022,N/A,183535,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Rural Population/Setting,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2017 +C15368,1R01AI166668-01,The Role of the Host Ubiquitin System in Promoting SARS-CoV-2 Replication and Pathogenesis,"The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) belongs to a family of pathogenic enveloped RNA viruses of the family Coronaviridae. The ongoing pandemic has caused a public health emergency worldwide, accompanied by dire health and economic consequences. There is evidence suggesting that CoV-2 may have relatively higher infection rates compared to previous epidemic strains of SARS and higher affinity to the receptor ACE2 than SARS-1. In addition, new CoV-2 variants have appeared recently with mutations that correlate with higher infection rates and the ability to escape specific immunity, causing major concerns. A major gap in knowledge remains as to how CoV-2 may have acquired the ability to spread more efficiently, and how new mutations may affect virus infectivity. The overarching goal of this proposal is to better understand the molecular mechanisms that regulate CoV-2 cell entry and replication, and how the appearance of new variants could lead to immune escape. We will focus on the role of the host Ubiquitin (Ub) system in promoting CoV-2 infection. This information could help predict appearance of more transmissible variants of coronaviruses, and to develop antiviral approaches by targeting specific steps of the ubiquitination process. Our data recently published in Nature, show that the envelope protein of flaviviruses is K63-linked polyubiquitinated, which enhances virus attachment to host cell receptors. Therefore, we asked whether a similar mechanism applies to SARS-CoV-2. Our preliminary data indicate that CoV-2 structural proteins are ubiquitinated on multiple lysine residue, some of which are not conserved in the original epidemic CoV strain. In addition, new variants of CoV-2 have appeared with mutations on these ubiquitination sites. Our data also suggest that ubiquitination of Spike (S) protein may play a role in stabilizing the CoV-2 S-ACE2 interaction, potentially leading to enhanced entry and pathogenesis. It is currently unknown whether any member of the Coronaviridae family, including SARS-CoV-2, utilize ubiquitination of viral structural proteins as a mechanism of virus attachment and entry. We have also identified E3-Ub ligases of the Tripartite Motif (TRIM) family of proteins, which ubiquitinates viral structural proteins. Our general hypothesis is that the variants of CoV-2 that have gained specific lysine residues provide new Ub acceptor sites on structural proteins, which can enhance virus replication and immune escape. By using in vitro biochemical approaches, novel recombinant mutant viruses, and in vivo models, we will assess how ubiquitination of structural CoV-2 proteins contribute to CoV-2 infectivity. In Aim 1 we will determine the mechanistic role of ubiquitination of the CoV-2 S protein in virus replication and antibody escape, and in Aim 2 we will determine the mechanistic role of ubiquitination of the CoV-2 Membrane protein in virus replication and IFN antagonism. The outcome of these studies may help explain how new more infectious viruses may appear by gaining ubiquitination sites and will provide the basis for the development of an antiviral approach that could be applied to a broad range of enveloped viruses.",2021,2026,N/A,483824,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +C15369,272201600013C-P00018-9999-12,MICROBIOLOGY AND INFECTIOUS DISEASES BIOLOGICAL RESEARCH REPOSITORY (MID BRR) - SARS-CoV-2 RESEARCH,"This contract provides unique and quality-assured infectious reagents and resources to the scientific community for use in basic research and product development. The scope of this contract includes the acquisition, authentication, production, preservation, storage, and distribution of research and reference reagents to the research community. These reagents span the pathogens in the Division of Microbiology and Infectious Diseases portfolio, and include the National Institutes of Allergy and Infectious Disease (NIAID) Category A, B and C Priority Pathogens and emerging infectious diseases.",2020,2020,N/A,1000590,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,,,2020 +C15370,1R21AI162662-01,"A general, virus-free platform to rapidly map SARS-CoV-2 drug resistance","PROJECT SUMMARY Development or repurposing of drugs for SARS-CoV-2 that causes COVID-19 is an active area of research, but not much effort is being spent on developing platforms to identify mutations that may merge to the inhibitors or neutralizing agents for these targets. Given the widespread prevalence of SARS-CoV-2 and potential abuse of developed therapeutic agents, the emergence of such escape mutants is likely. We will develop a virus-free platform to identify and validate escape mutants for therapeutic agents in the pipeline for SARS-CoV-2.",2021,2023,N/A,234243,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C15372,1R01AI166050-01,Defining the Translocation Mechanisms of SARS-CoV-2 nsp13 Helicase to Aid in Antiviral Development,"Project Summary SARS-CoV-2, the causative agent of COVID-19, has infected more than 103M people worldwide (February 2021) with more than 2.25M deaths, and represents a dire threat to the health and economic well-being of the entire world. Although vaccines seem to be effective against SARS-CoV-2, recent information regarding potential vaccine resistant strains highlights the importance of alternative strategies to combat this virus. The development of antiviral therapeutics on important mutation resistant viral proteins such as nsp13 is one such strategy. Improved knowledge of the molecular mechanisms utilized by nsp13 are necessary to rationally develop inhibitors. This project will address this deficiency utilizing an integrated multiscale modeling, protein crystallography, and biochemical approach to define how SARS-CoV-2 nsp13 helicase binds RNA and ATP substrates, transduces energy during ATP binding and hydrolysis, and changes conformation during ligand binding and catalysis. We propose the following: 1) Identification of molecular-level components of the RNA- binding and translocation mechanisms of nsp13. Preliminary all-atom molecular dynamics (aaMD) simulations of SARS-CoV-2 nsp13 have identified key protein-RNA interactions that will inform initial mutagenesis studies. Further simulation and protein crystallography will inform on the ATP-dependent protein-RNA interactions observed in the RNA cleft. Biochemical experiments will be performed to test the structure-function hypotheses generated by the structural-based approaches. 2) Identification of molecular-level features of the binding, hydrolysis and product release of ATP by nsp13. We have performed aaMD simulations of the SARS- CoV-2 nsp13 in all relevant substrate states. Soaked-in ATP and non-hydrolysable analogue protein crystallography will be performed to test these initial models. Subsequent quantum mechanical calculations will identify key components of the ATP hydrolysis reaction. Site-directed mutagenesis and well-established enzyme kinetics assays will be used to test effects predicted by these simulations. 3) Identification of allosteric networks in SARS-CoV-2 nsp13 that transduce energy from ATP binding and hydrolysis to perform RNA translocation. Utilizing network analyses of aaMD simulations, Motif V has been identified as a key allosteric contributor. Biochemical studies will be performed to verify that Motif V is necessary for nsp13 helicase function. Further work will be done to identify allosteric networks between additional components of the ATP pocket and RNA cleft identified in Aims 2 and 3. This work will produce unprecedented molecular-level insight into the translocation mechanism of SARS-CoV-2 nsp13 helicases. Key components of this mechanism represent new targets for antiviral development.",2021,2026,N/A,479232,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C15373,1R21NS122280-01A1,Synergistic Interactions of SARs-CoV2 and environmental toxicants in Experimental Parkinsonism,"ABSTRACT Approximately16.5 million people have been infected with the SARS-CoV2 virus with approximately 650,000 (and rising) deaths. While primarily a respiratory virus, clinical observations appear to demonstrate nervous system involvement. These include those associated with the CNS (headache, confusion, seizure, stoke), PNS (pain, anosmia, ageusia) and enteric nervous systems (ENS, diarrhea). What is not fully understood- at this time- is how the SARS-CoV2 virus produces these nervous system disorders. We also do not know if the impact(s) on the nervous system will persist, or possibly even become apparent, post infection. Previous studies in my lab examining neurotropic (H5N1 influenza, western equine encephalitic virus) and non-neurotropic (pandemic H1N1 influenza) have shown that each can produce immediate and/or delayed effects in the CNS, including induction of pathologies seen in Parkinson's disease. Related to SARs-CoV2, a number of recent studies, using autopsy material has examined the localization of SARS-CoV-2 virus in the brain. From these studies, approximately 36% had apparently low levels of viral SARS-CoV-2 RNA and protein in brain, although in each of these studies a complete cellular and localization map have not been reported. Also, it is not known if the viral particles found in the CNS were present intracellularly due to inherent neurotropism or were only present in the CNS due to breaches in the cerebral vasculature. (i.e., secondary to cerebrovascular damage). Even without neurotropism, an understanding of changes in the nervous system are critical since it is that any immediate and/or delayed effects may result from dysfunctional signals (peripheral cytokine storms) that arise outside of the nervous system; yet impact the function and, perhaps, survival of neurons. To address these unanswered questions, two specific aims are proposed. In Specific Aim 1, we will empirically determine the neurotropic potential of the SARS-CoV2 virus (USA-WA1) throughout its natural period of infection in the CNS, PNS and ENS in C57BL/6J mice and C57BL/6J mice expressing a human ACE2 receptor (K18-hACE2, B6.Cg-Tg(K18-ACE2)2Prlmn/J). We will also examine the induced inflammatory response in the periphery and brain. In Specific Aim 2, we will determine if resolved SARS- CoV2 infection can sensitize SNpc DA neurons to agents that have been shown to induce parkinsonism (paraquat and rotenone) in mice and humans as well as if it can exacerbate the spread and extent of alpha-synuclein pathology. These aims and associated experiments will allow us to directly determine the neurotropic and immunogenic potential of SARS-CoV2. They will also allow us to determine this virus has the potential to sensitize neurons to exogenous insults as has been demonstrated with some other respiratory viruses. Understanding if this pandemic virus affects the CNS and in particular, the basal ganglia is important for both short term treatment as well as longer-term management of post infection effects. Additionally, understanding the neuropathological sequalae of SARS-CoV2 on the nervous system will be necessary for later studies examining if a therapeutic intervention (i.e. vaccine or modulator of inflammatory response) can protect against primary and/or secondary nervous system effects of this respiratory infection.",2021,2022,N/A,429000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,Clinical characterisation and management,Disease pathogenesis,2021 +C15374,3P30DK111024-06S1,Impact of Community Health Worker Home Deployment on COVID-19 Vaccine Confidence and Uptake,"PROJECT SUMMARY / ABSTRACT In response to NOT-OD-21-101, the Georgia Center for Diabetes Translation Research (P30DK111024-05S1), a partnership of Emory University (EU), Morehouse School of Medicine (MSM), and Georgia Institute of Technology submits this RADx-UP Supplement proposal titled, ""Impact of Community Health Worker Home Deployment on COVID-19 Vaccine Confidence and Uptake."" We propose collaborating with our RADx-UP Diabetes rural community partner and utilizing locally developed and tested Georgia CEAL (1OT2HL156812- 01/16-312-0217571-66105L, PI-Akintobi) COVID-19 communication materials to enhance COVID-19 testing in addition to vaccine confidence and uptake in underserved populations most severely affected by COVID-19 disease (i.e., African Americans and Latinos with diabetes, prediabetes, and their household contacts [""bubble""]). The proposed 1-year project will implement and evaluate a brief Community Health Worker (CHW) intervention through the Albany Area Primary Health Care, a rural Federally Qualified Health Center (FQHC). The primary goal of this study is to maximize effective outreach, education, and communication through CHWs in order to facilitate improved COVID-19 vaccine confidence and uptake in underserved and vulnerable communities. CHWs will be deployed to the homes of adults with increased risk of morbidity and mortality (i.e., African Americans or Latinos with uncontrolled diabetes or prediabetes, age <50 years, and non-COVID-19 vaccinated) in order to educate them about diabetes, COVID-19 and related vaccines. Health assessments, including blood glucose measurement, will be conducted on the indexed patient and offered to all other adult family members in the household (i.e., ""bubble""). Adults with Type 2 diabetes likely live in households with other adults who have or are at increased risk for diabetes (i.e., prediabetes and obesity).1 It is expected that they will also share similar COVID-19 exposure risk. The specific aims are to: 1) Evaluate a community-driven education program to increase and enhance COVID-19 vaccine confidence and uptake in individuals with uncontrolled diabetes and their families (i.e., their ""bubble"") and 2) Evaluate a community-driven education program to improve diabetes self-management behaviors and related outcomes (e.g., blood glucose) in individuals with uncontrolled diabetes in rural, Southwest Georgia.",2021,2026,The Georgia Center for Diabetes Translation Research,300000,Human Populations,Black | Other,Adults (18 and older),Rural Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2016 +C15375,3U01HL146204-03S1,Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS),"COVID Vaccine Study Supplement to MWCCS Principal Investigators: C. Rinaldo and J. Martinson Innovation Fund Application to the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS): COVID-19 Vaccine Acceptance and Hesitancy (CVHB) Study in People with HIV Scientific Justification A safe, highly immunogenic vaccine to prevent primary SARS-CoV-2 infection is needed to control the COVID-19 pandemic. As of January, 2021, the United States is racing to vaccinate a significant percentage of our 330 million population to control the COVID-19 pandemic. This extraordinary rapid development resulted from FDA emergency use authorization (EUA) of two COVID-19 vaccines in December, 2020, i.e., the Moderna mRNA-1273 vaccine that codes for the stabilized pre-fusion SARS- CoV-2 spike protein 1, and the Pfizer/BioNTech vaccine BNT162b1 that is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain of the spike glycoprotein of SARS-CoV-2 2. Despite this enormous public health issue of stopping the COVID-19 pandemic, there are essentially no data on COVID-9 vaccine acceptance or efficacy in people with HIV (PWH). This is critically important for public health, in that an estimated 1.2 million people aged 13 and older have HIV in the United States, including an estimated 161,800 (14%) people whose infections had not been diagnosed 3. Although several COVID-19 vaccine clinical efficacy trials enrolled PWH without specific selectivity, there are insufficient data exist to determine the efficacy of COVID-19 vaccines in PWH. Indeed, prior to the COVID-19 pandemic, the CDC recommended that PWH with CD4 T cell counts of ≥200 or percentages ≥15% receive all licensed vaccines. Further, the CDC stated in a release December 12, 2020 (https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-12/slides-12-12/COVID-03- Mbaeyi.pdf): ""The recently FDA-authorized Pfizer-BioNTech COVID-19 vaccine is not contraindicated for people living with HIV or others with immunocompromised conditions, though vaccine efficacy data does not currently exist for potentially immunocompromised individuals"". According to the CDC Advisory Committee on Immunization Practices (ACIP), ""people living with HIV may still receive the vaccine, but should be counseled on unknown vaccine safety and efficacy profiles in immunocompromised persons."" The ACIP also recently recommended that health care personnel and residents of long-term care facilities (LTCFs) be offered vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a) 4. In sum, PWH are looking to us for advice as their scientific and clinical HIV experts, with our response being that the COVID-19 vaccines ""should be"" safe and effective in them based on no specific data. Our proposed study aims to supply such data through a well-designed protocol nested in the most well-established and trusted MACS-WIHS Combined Cohort Study (MWCCS).",2021,2026,N/A,40374,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Clinical trial (unspecified trial phase) | Vaccine/Therapeutic/ treatment hesitancy,2019 +C15376,1R01AI159945-01,Investigating Interferon Antagonists in Delaying Innate Immune Responses to SARS-CoV-2,"TITLE: Investigating Interferon Antagonists in Delaying Innate Immune Responses to SARS-CoV-2 PI: Susan C. Baker, PhD, Loyola University Chicago Stritch School of Medicine The goal of this proposal is to determine how viral interferon antagonists function in the replication and pathogenesis of coronaviruses, particularly during replication of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses (CoVs) are a diverse family of positive-sense RNA viruses that include pathogenic strains infecting human and animal hosts. CoVs have repeatedly jumped from animal reservoirs into human circulation, causing severe disease and pandemics, as we are currently experiencing with SARS-CoV-2. Developing appropriate protective measures against emerging CoVs, including SARS-CoV- 2, will depend upon gaining an understanding of coronavirus-host interactions. We discovered that the endoribonuclease (EndoU), a highly conserved component of the CoV replicase complex, reduces dsRNA species recognized by host pattern recognition receptor MDA5, delaying the induction of interferon. We reported that viruses expressing an inactive form of EndoU replicate as efficiently as wild type virus in IFN non- responsive cells. Importantly, replication of EndoU mutant CoVs in interferon-responsive cells activate robust immune responses, which extinguishes virus replication and reduces pathogenesis in animals. Recently, we identified the target of EndoU activity to be poly-uridine containing negative sense RNA, which we term PUN RNA. This removal of the PUN RNA delays the generation of dsRNA species that are recognized by host pattern recognition receptor MDA5. We hypothesize that EndoU activity contributes to the delay in the innate immune response to SARS-CoV-2 replication. Here, we propose to investigate the mechanism of how EndoU acts in SARS-CoV-2, how EndoU associates with the replicase complex, and how PUN RNA contributes to activating MDA5. In Aim 1, we will evaluate EndoU and other IFN antagonists for their role as modulators of Type I and Type III IFN responses to SARS-CoV-2 infection in primary human airway cells and in enterocytes. We will use reverse genetics to generate viruses with inactive IFN antagonists and evaluate the effects of combining inactivation of EndoU with inactivating mutations of other viral protein IFN antagonists. In Aim 2 we will delineate and disrupt EndoU interactions within the coronavirus replicase complex. The results of these studies will guide strategies for disruption of EndoU from the CoV replicase complex, which would activate protective immune responses to CoV infections. In Aim 3, we will identify regions of poly-uridine negative-sense RNA, termed PUN RNA, required for recognition by EndoU and MDA5. These studies will provide new information on how PUN RNAs are recognized by EndoU and MDA5. Overall, these studies will define a new mechanism for how an endoribonuclease acts as a virulence factor. This new information can be used to develop antiviral therapies and vaccines against existing and emerging coronaviruses.",2021,2026,Loyola University Chicago Stritch School of Medicine,789887,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +C15377,1R21AI163656-01,PET imaging of viral infection,"Many viruses sustain a parasitic lifestyle by exploiting host cell supplies of nucleotides for replication. The manifestation and progression of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 (SARS2), an RNA virus, is accompanied by the expansion of the virus in the infected host using host's machinery. The rapid SARS2 expansion requires augmented RNA synthesis via the salvage pathway of RNA synthesis, most especially in the non-dividing cells that are the targets of SARS2 infection. This provides an opportunity to trace the status of viral infection if an imaging tracer that is indicative of viral RNA synthesis is available. Similar to the host, viral related RNA synthesis (viral genomic RNA or viral messenger RNA) occurs in three stages: initiation, elongation and termination. We will focus on the elongation of viral related RNA synthesis, which is the repeated addition of a nucleoside monophosphate (NMP) to the 3' end of the growing RNA chain. Since SARS2 requires massive amounts of host cell uridine, 1/3 of its genome is uridine, uridine is moreover required for sub-genome positive strand RNA synthesis/viral function. Accordingly, radiolabeled uridine shall be used to track pyrimidine metabolism by PET imaging for augmented RNA synthesis under SARS2 infection. However, the specific salvage pathway of uridine metabolism for incorporation into viral RNA synthesis was not up-regulated in SARS2 infected tissues. Yet, 5-FU can be converted directly into uridine monophosphate (UMP) for incorporated into RNA. We therefore propose to use F-18 labeled pro-drug 5- fluorouracil (5-[18F]FU, the same molecule as 5-FU with isotopic substitution of F-19 by F-18) instead. Still, the rapid catabolism of 5-[18F]FU obscures interpretation of the PET images until the addition of eniluracil (5-ethynyluracil) that prevents the catabolism of 5-[18F]FU to obtain meaningful PET images of 5- [18F]FU uptake. Consequently, we propose to re-purpose 5-[18F]FU for PET imaging of SARS2 infection, and will use the same eniluracil to transiently maintain the integrity of 5-[18F]FU during the proposed PET imaging. We will test PET imaging with 5-[18F]FU using the readily available and clinically relevant model of mouse hepatitis virus (MHV) infection. MHV, a murine coronavirus very similar to SARS2 in structure, can cause a wide range of diseases in the mice and rats, including hepatitis, encephalomyelitis, enteritis, and, respiratory diseases. Many of these same organs were similarly affected during human SARS2 infection even though the acute lung injury related mortality symbolized COVID-19 in the public perception. Clinical utility of 5-[18F]FU PET imaging would be complementing PCR-based testing of COVID-19 (gold standard) or CT-based assessment (non-specific evaluation) of related lung disease. It could also be used to facilitate new anti-viral drug development (beyond remdesivir) for optimizing therapeutic dose and treatment duration, and for treatment monitoring in the future.",2021,2023,N/A,201250,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2021 +C15379,3U54GM104941-09S1,"Improving Pediatric COVID-19 Vaccine Awareness, Access, and Accountability in Underrepresented Communities","Abstract-Overall This proposal is a competitive renewal of the IDeA Program Infrastructure for Clinical and Translational Research (IDeA-CTR)(U54) grant originally awarded in September 2013. The program, titled the Delaware CTR ACCEL Program, has thus currently completed four years of funding at the time of this application. The overall goal of the ACCEL Program remains to provide the key components to allow growth in strategic areas to improve the health of the citizens of Delaware and the nation. Our consortium currently consists of four partners: University of Delaware (UD)-the lead institution; A.I. DuPont Hospital for Children, a part of the Nemours Children's Health System (Ne- mours); Christiana Care Hospital System (CCHS), the largest health care sys-tem in the state of Delaware; and the Medical University of South Carolina (MUSC), our out-of-state IDeA partner. In this competitive renewal, we will expand our consortium to include Delaware State University (DSU), an American historically black, public univer- sity located in Dover, Delaware. Delaware is an ideal state for a CTR grant as it represents the whole of the USA in a compact form. The population of Delaware (~950,000) mirrors the US population in urban-to-rural citizen ratio and ethnic/racial diversity, with 22% African American, 69% Caucasian, 8% Hispanic, 3% Asian and 1% Native American. The dominance of adult (CCHS) and pediatric (Nemours) hospital systems, which serve at least 85% of the residents of the state, provides a unique opportunity to treat the state of Delaware as a model for examining how healthcare changes can impact population health. Similar to the strong support the ACCEL Program currently enjoys, the part- nering institutions and the State have again agreed to provide over $8.3 M in funds to support ACCEL related activi- ties. The structure and activities of the ACCEL Program have been modified in this competitive renewal. The ACCEL Program now only includes the Administrative Core and the five required key component activities. In addition, based on lessons learned, opportunities discovered, and success achieved, we have made substantive exciting changes to every component of the ACCEL Program. The Overall Specific Aims for the ACCEL Program are to: 1) Provide op- portunities and infrastructure that enhance the ability of outstanding investigators to conduct exciting and impactful clinical and translational research programs in areas of need and opportunity. 2) Recruit, train, and develop clini- cians, scientists, and engineers who will develop innovative, competitive, interdisciplinary, and interinstitutional clin- ical and translational research teams, and 3) Expand and enhance model community engagement outreach research programs that work with the State and other stakeholders to promote health and wellness to a diverse population of Delawareans. The leadership of the ACCEL program is proud of the strong foundation we have created over the past four years and looks forward to continuing to grow clinical and translational research programs that address some of the most important health care needs of Delawareans and all Americans.",2021,2023,University of Delaware (UD),287168,Human Populations,Asian | Black | White,Children (1 year to 12 years),Rural Population/Setting | Urban Population/Setting,Minority communities unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health workforce,2013 +C15380,1R03EB032118-01,Developing a Mechanical Emulator to Simulate SARS-CoV-2 Droplet Cloud Formation and Propagation,"Project Summary Our understanding of pathogen laden droplet/particle cloud formation and propagation remains limited. Several approaches including use of computational tools, experimental tests by tracking ejected droplets from subjects during emissions, and limited simulators by pumping and dispersing powders, have been implemented. Yet there is no adequate respiratory emission emulator that could holistically replicate saliva liquid atomization and the breakup process corresponding to each main explosive event such as sneezing, coughing, or speaking loudly. In this proposal, our overarching aim is to fill this gap by developing and testing a spray system that emulates respiratory events. This device can be used as an alternative subject to mimic the main respiratory events with higher flexibilities in terms of availability/safety, superior droplet tracking, and wider representation of subjects. To develop this new device, three specific aims are proposed: Aim 1. Design and fabricate the emulator spray system capable of simulating respiratory events in terms of droplet size & velocity distributions and counts of the formed droplet cloud. The system includes a hardware and a PC-based control unit to enforce desired air pressure profile, particular to each type of emission and ensued droplet cluster. Aim 2. Characterize emulator ensued plume and compare it to ejected droplet cloud from actual respiratory emissions using high-speed imaging and laser diffraction. Aim 3. Find relevant pulsating pressure and flowrate profiles to emulate typical explosive respiratory events. The long-term goal of the project is to add more features to the device (e.g. adding motions) to gradually approach the actual phenomena. This novel proposed emulator can be used to mimic flow and evolution of pathogen laden droplets; therefore, it provides opportunities for training healthcare workers and the public on the best preventative practices and design of adequate ventilation systems. Furthermore, the project aids faculty and underrepresented students at Tuskegee University (a Historically Black University) in developing/testing a novel mechanical emulator to better understand a virus propagation route through engineering tools. It also helps students to see how engineering and other disciplines can come together and contribute to a public health crisis. 1",2021,2023,Tuskegee University,68988,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,Innovation,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15381,1R21EB031597-01,Design and evaluation of a multivalent nanobody construct for prevention or treatment of SARS-CoV-2,"Abstract SARS-CoV-2 has spread rapidly across the globe. While vaccines are in development and existing drugs have shown some efficacy in reducing disease severity, there is an urgent need for molecules that can serve in both a prophylactic and therapeutic function. Proteins are well suited for this task because they can be engineered to have high-specificity and high-affinity for targets, and genetic protein fusion bestows multiple functions on a single protein molecule. A nanobody (Nb) has been identified with high affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates viral entry into cells via the angiotensin converting enzyme 2 (ACE2) receptor. Nbs are small heavy chain, single domain camelid antibodies that are stable over wide conditions, express well in multiple systems, can be humanized to reduce immunogenicity, and can be fused to other proteins. The goal of this proposal is to develop a protein-based therapeutic platform that can be taken either prophylactically or post-infection to reduce the severity of viral infection. The overall hypothesis is that a self-assembling hexameric coiled-coli (Hex) can be fused to 12-24 anti-RBD Nbs to create a complex with high avidity that will neutralize virus and prevent entry and/or aggregate virus into traps that can be cleared. Further, anti-albumin Nb will be incorporated in the fusion design to investigate any benefit of increased circulation time. Three aims have been set to meet the goal and test the hypothesis. (1) Design, fabricate and characterize Hex-Nb assemblies made from fusion proteins with different numbers of anti-RBD and anti-albumin Nbs. (2) Characterize binding, neutralization, and trapping of SARS-CoV-2 pseudovirus by Hex-Nb fusion assemblies in vitro. (3) Determine pharmacokinetics, biodistribution and humoral immunogenicity of Hex-nanobody fusion protein in mice following intravenous injection. From this work, an innovative protein-based therapeutic will be constructed from functional nanobodies that inhibits SARS-CoV-2 pseudovirus infection and extends in vivo lifetime, providing proof of concept for Hex assemblies to serve as prophylactics or therapeutics to prevent or treat viral infections. These results will enable future preclinical work, including viral challenge studies and direct airway administration of the Hex-Nb assemblies. Overall, this work will provide a strategy to respond to both the current and future pandemics with highly multivalent engineered protein complexes.",2021,2023,N/A,397382,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +C15382,3P20GM125498-04S1,Multi-Scale Modeling of SARS-CoV-2 Dissemination Dynamics,"PROJECT SUMMARY - Overall Component Despite striking advances in the 20th and early 21st century, infectious diseases are dynamic, ever-evolving global threats that cause significant morbidity and mortality in all populations worldwide. Within a single year, Zika has emerged, massive outbreaks of cholera have occurred, and antimicrobial resistance has become a critical international concern. This landscape demands new approaches to prevent and control infectious diseases, and the training of new scientists to meet these demands. New approaches will require interpretation of big data sets, including data from both the biologic sciences (""systems biology"" and ""-omics"") and advanced epidemiology. This University of Vermont COBRE will be focused on Translational Research to Prevent and Control Global Infectious Diseases. ""The TGIR Center"" (Translational Global Infectious Diseases Research) will integrate a novel multi-disciplinary research team of biomedical and mathematical/computational scientists. The team will work toward novel and impactful research to diminish the burden of globally-important infectious diseases by bridging the culture gaps between the biologic and mathematical/computational fields of biomedical research. Our center will leverage substantial existing strengths at UVM in Global Infectious Diseases Research, and strengths in complex systems and computational modeling. A team of experienced directors, scientific advisors/mentors, and two new core facilities (""Mathematical and Computational Predictive Modeling"" and ""Human and Population Research""), will foster collaborative and novel research. The TGIR will develop four outstanding, existing junior faculty under the mentorship of senior scientific advisors from three UVM colleges and five departments. Institutional support will enable recruitment of three new junior faculty and will provide space for a new Innovation and Collaboration laboratory, the latter also supported by the proposed Alteration and Renovation component. Internal and external advisory committees will provide formal, unbiased oversight. Junior faculty will find a robust, well-organized academic home in the TGIR COBRE: a strong mentoring and career-development program, a center-wide seminar series and coursework, and research support from multi-disciplinary senior faculty teams in both research cores.",2021,2023,This University of Vermont,322445,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2018 +C15383,3R25GM129218-05S1,The Science of COVID-19 Vaccines,"This request for supplemental funds will allow us to expand and refine instructional materials addressing the science of coronavirus and the role that vaccines can play in eradicating this virus. Instructional materials that will be created with these supplemental funds include (i) a video that specifically addresses the science behind current vaccine development efforts and their testing in clinical trials, (ii) physical models of coronavirus,... enhanced with augmented reality technology (iii) new molecular landscape posters (featuring the art of David Goodsell) that present engaging images of a coronavirus within a respiratory droplet and the structure of an mRNA vaccine and (iv) a condensation of the AeroNab story into a video targeted to the general public. The materials created in tis project will be made available to underserved minority students in both urban and rural settings.",2021,2022,N/A,53568,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Rural Population/Setting | Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication,2017 +C15384,3R25GM129873-04S1,K-12 Educational Resources on Vaccine Biology and SARS-CoV-2 Vaccine Hesitancy,"Abstract The goal of this project is to develop innovative educational resources aimed at rural middle school-age children and medically underserved populations to increase vaccine confidence and encourage vaccine acceptance by the public. To attain this goal, an interdisciplinary team of scientists and education and communication specialists has been assembled. This project will undertake three specific aims. Specific Aim 1 will compile information on vaccine hesitancy (history, reasons for, approaches for overcoming, and vaccine myths and misconceptions) to help inform information delivery. Specific Aim 2 will produce age-appropriate materials (high quality brochures and posters, interactive digital media, etc.) to provide general factual information on vaccine biology, including basic biology (mRNA), basic immunology, and how vaccines are developed and manufactured. Specific Aim 3 will be directed at innovative packaging of the factual information produced in Specific Aims 1 and 2, with delivery of this information into rural schools/regions, including vulnerable populations in South Texas. The newly developed materials will increase general literacy on immunology and on vaccine research and development, manufacturing, and testing, with the goal of allaying fears and concerns about vaccines. For example, entertaining but informative videos and webcasts will be distributed via social media, as public service announcements, or used in classrooms. In these, a person (undergraduate, graduate or veterinary student) posing as vaccine hesitant interviews an expert with a script that addresses hesitancy and misconceptions. These materials will be made available to middle school teachers throughout the USA via the extensive network already established by the Partnership for Environmental Education and Rural Health (PEER) program. TAMU Biomedical Sciences (BIMS) undergraduate students will also disseminate the educational materials into local rural schools as near- peer communicators. Furthermore, use of social media will allow PEER to reach audiences around the world. Capitalizing on Rogers's Diffusion of Innovations Theory, existing networks between teachers, middle school students, and their families will be used. Bilingual middle school children will receive information that they can bring back to their Spanish-speaking parents and other community members.",2021,2023,N/A,53536,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Rural Population/Setting,Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,,,,,United States of America,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2018 +C15385,3U54GM133807-02S1,SARS-CoV-2 genomic surveillance across the island of Puerto Rico,"Improving health care for the medically underserved, including our Hispanic population, afflicted by prevalent diseases, such as cancer, cardio-metabolic and infectious diseases, remains a major challenge. The current application is to support the development of Hispanic Alliance for Clinical & Translational Research in Puerto Rico (Alliance), which aims to build on the existing infrastructure of the Puerto Rico Clinical and Translational Research Consortia (PR-CTRC an RCMI-CTR) and the unique expertise on emerging infectious diseases and the study of disaster-related conditions and their impact on Health. The objective of the Alliance is to serve as the catalytic center to enhance the competitiveness of investigators to conduct research and obtain additional funding for clinical and translational research addressing highly prevalent diseases and those that affect the medically underserved in Puerto Rico. The long-term goal of the Alliance is to transform clinical and translational research in Hispanic populations in the Mainland and in Puerto Rico by promoting inter-disciplinary collaboration and leverage of resources to address diseases affecting Hispanic communities. Successful implementation of the Alliance will advance our fundamental knowledge of Hispanic health in this ethnic subgroup, which is increasingly represented in the U.S. mainland population. The Alliance is innovative because it will: (1) create a Hispanic-centered research hub integrating resources to support researchers in PR and national partners; (2) implement the Hispanic Real World clinical research data warehouse; and (3) establish a Community Health & Research Council comprised of diverse community partners emphasizing a community-centered, bi-directional research focus to impact health policy and ultimately improving health outcomes in our Hispanic community. The Alliance overall aims are specified below. Specific Aim 1: Enhance an island-wide infrastructure and human resource network and synergize with local and national partners to conduct clinical and translational research in Puerto Rico. Specific Aim 2: Provide professional development activities to enhance the ability of investigators to develop competitive clinical and translational research programs with emphasis on Hispanic health needs. Specific Aim 3: Facilitate the generation and dissemination of knowledge to and from the bench and the community to improve health outcomes that affect Hispanic communities in Puerto Rico and across United States. Specific Aim 4: Catalyze and sustain the integration of trans/multi/inter disciplinary collaborations to conduct clinical and translational research within and across institutions, organizations, community networks and health programs in Puerto Rico and other IDeA states.",2021,2025,N/A,745055,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,Americas,Data Management and Data Sharing,,,,United States of America,,,2020 +C15423,unknown,PROMISE Preparing for RSV immunisation and surveillance in Europe,"Respiratory syncytial virus (RSV) is an infectious disease that can cause severe illness in young children as well as the elderly and people with weakened immune systems. Globally, an estimated 33 million young children are diagnosed with RSV every year, and over 3 million are hospitalised. Currently, there is no vaccine or treatment for RSV, although a number of products are in clinical trials or earlier stages of clinical development. The aim of PROMISE is to significantly advance our understanding of RSV to aid in the design of public health strategies as well as the development and use of vaccines and therapeutics in both children and older people. It builds on the work of IMI's RESCEU project, which has delivered significant insights and resources on RSV. The project plans to address current knowledge gaps on RSV, such as the relationship between RSV infection and school age wheeze and asthma. They will also identify new diagnostic tools and study biological markers of RSV infection. In addition, the project will develop a surveillance network on RSV, a resource that will provide valuable information on respiratory infections in the community. Finally, PROMISE will attempt to evaluate the impact of COVID-19 on the spread of RSV, especially among older adults.",2021,2024,N/A,8540952.15,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C15469,unknown,A mixed-methods study on the design of AI and data science-based strategies to inform public health responses to COVID-19 in different local health ecosystems within Colombia,"Vulnerable communities in Colombia are affected not only by the coronavirus disease, but also by disinformation about the pandemic. Universidad de los Andes will develop Al models to shed light on the risk of disease progression to vulnerable communities and its impact on other diseases. They will also address the ""infodemic"" by analyzing popular social networks, users who act as ""super spreaders"" of information and misinformation, and common reactions to policies and events of social importance.",2021,-99,Universidad de los Andes,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Colombia,Colombia,"Policies for public health, disease control & community resilience",Communication, +C15470,unknown,"AI and data science for early detection of potential epidemic and pandemic outbreaks after COVID-19: Implementation of a scalable strategy of electronic, gender-inclusive, and socially responsible medical records","CIECTI will leverage electronic health records to pilot new models to support early COVID-19 detection in communities, improve data collection in vulnerable communities, and work with the National Ministry of Health to contain the disease.",2021,-99,"Centro Interdisciplinario de Estudios en Ciencia, Tecnología e Innovación (CIECTI)",,Other,Not applicable,Not Applicable,Unspecified,Vulnerable populations unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Argentina,Argentina,Epidemiological studies,Disease transmission dynamics, +C15471,unknown,Predictive modeling and forecasting of the transmission of COVID- 19 in Africa using AI,"York University has joined forces with epidemiologists, modelers, physicists, statisticians, software engineers, and data scientists across Africa to integrate the power of predictive modelling and simulations with the capacity of a comprehensive COVID-19 monitoring dashboard that will be used to predict epidemic trends and inform decision-making and real-time management across Africa.",2021,-99,York University,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics, +C15472,unknown,Uses of AI in the fight against COVID-19 in Senegal and Mali: Adaptability to the local context and social acceptability for ethical and responsible AI,"While Senegal and Mali are eager to use AI methods to improve contact tracing efforts, the countries contend with a number of social and political challenges. This research will support epidemiological modelling of COVID-19 in Senegal and Mali while addressing the social and political obstacles in connection with the use of AI technologies and health control measures within a framework of ethics and human rights.",2021,-99,Université Cheikh Anta Diop,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Senegal,Senegal | Mali,Epidemiological studies | Research to inform ethical issues,Disease transmission dynamics | Research to inform ethical issues related to Public Health Measures, +C15473,unknown,"AI framework for threat assessment and containment for COVID-19 and future epidemics while mitigating the socio-economic impact to women, children, and underprivileged groups","These new modelling efforts will focus on supporting Malaysian and Sri Lankan efforts to map the COVID-19 crisis and mitigate COVID-19's economic impacts on women, children, and underprivileged groups.",2021,-99,University of Peradeniya,,Human Populations,Unspecified,Unspecified,Unspecified,Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,South-East Asia,South-East Asia | Western Pacific,,,,Sri Lanka,Malaysia | Sri Lanka,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C15474,unknown,"Leveraging AI and data science techniques in harmonizing, sharing, accessing and analyzing SARS-COV-2/COVID-19 data in Rwanda","Government and other public health institutions are calling for initiatives that can support the increased availability of data to support evidence-based policymaking. However, much of the available data is fragmented, incomplete, and scattered across multiple institutions such as clinics, hospitals, and testing sites. This project will innovate to harmonize data to understand and predict the impact of COVID-19 and other infectious diseases. It will also focus on new innovations to make best use of the data to advance policy and care decisions.",2021,-99,University of Rwanda,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Data Management and Data Sharing,,,Rwanda,Rwanda,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C15475,unknown,End-to-end AI and data systems for targeted surveillance and management of COVID-19 and future pandemics affecting Uganda (COAST),This project aims to deliver a set of contextualized and equitable end-to-end AI and data systems that target the surveillance and management of COVID-19 and future pandemics that may affect Uganda. The project will focus on using AI systems to analyze radio conversations to improve understanding of and to address public perceptions of COVID-19 and interventions aimed at understanding their connection with COVID-19 transmissions and interventions. It will also explore new innovations for diagnosing and treating COVID-19 using AI tools to support screening.,2021,-99,Makerere University,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Innovation,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Diagnostics | Disease transmission dynamics | Impact/ effectiveness of control measures | Communication, +C15476,unknown,Harnessing COVID-19 data to support public health and economic decision-making in Kenya and Malawi,"This project will harmonize data to compare and understand the impacts of different public health decisions taken in Malawi and Kenya. It seeks to understand COVID-19 transition dynamics and their impact on health, education, work, and transport, including how interventions work and where they work best.",2021,-99,African Population and Health Research Center (APHRC),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,,,,Kenya,Malawi | Kenya,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts, +C15477,unknown,"Harnessing heterogeneous COVID-19 data, to build a data hub and apply artificial intelligence (AI) and data science to support public health and economic decision makings in Kenya and Malawi","This project proposes to develop the key elements of a coordinated pan-African COVID-19 data ecosystem. We will build a robust suite of data standards and technologies, diverse data integration methodologies, using the power of AI and data science for analysis and oversight through a trusted governance and policy environment. The harmonized data represents a global public good which will deliver insights for evidence-based answers on key questions about COVID-19.",2021,-99,African Population and Health Research Center (APHRC),,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Africa,Data Management and Data Sharing,,,Kenya,Malawi | Kenya,"Secondary impacts of disease, response & control measures",Economic impacts, +C15853,21/04914-3,"Modeling of congenital disease caused by the Zika Virus in the CNS in 2D/3D models: the initial objective, in addition to the Zika Virus, was expanded to study aspects related to the SARS-COV-2 Coronavirus",The mechanisms involved in the pathogenesis of ZIKV and SARS-COV-2 in the CNS will be evaluated using 2D models of human cells and 3D brain organoids derived from iPSC. The study will also involve the use of in vivo models to validate prevention (vaccines) and treatment (drug) strategies. (AU),2021,2023,Centro de Inovação da USP (INOVA). Universidade de São Paulo (USP),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Disease pathogenesis | Pre-clinical studies | Pre-clinical studies,2021 +C15854,20/09064-5,Cardiorespiratory telerehabilitation for patients after hospitalization for COVID-19 in Brazil: randomized clinical trial,"Introduction: Although there is a lack of studies with specificities regarding post-COVID 19 clinical condition, patients who survive the acute condition are likely to suffer with post intensive care syndrome. Hence, they may experience respiratory, motor and psychological impairments, which should be addressed by long-term rehabilitation programs (RP). These programs aim to increase the chances of recovering from this syndrome. However, the offer to RP is worrying nationally and internationally, since, even in non-pandemic periods, there is an important deficit in the number of rehabilitation center opportunities. Considering the increase in the need of rehabilitation after COVID-19, there may happen a collapse in RP system. Moreover, there is a lack of consensus regarding the time after symptoms disappearance patients are still contagious, thereafter, distance RP (telerehabilitation) presents as an adequate tool, however, it must be tested before its implementation. Objectives: Study 1: to characterize physiological responses during the execution of activity daily life (ADL) in patients post-hospitalization for COVID-19. Study 2: to verify the effectiveness of cardiorespiratory telerehabilitation protocol in patients after COVID-related hospitalization. Methods: Individuals after COVID-19 related hospitalization will be assessed regarding eligibility criteria. For sample size will be executed a pilot study. Study 1 will be a longitudinal observational study and study 2 will be a randomized controlled trial coordinated by the Physiotherapy Department of the Federal University of São Carlos regarding a virtual domiciliary RP involving accessible and functional activities. The primary outcome will be functional capacity verified by physical tests. Expected results: we expect with study 1 to understand post-COVID-19 patient's PADL through an analysis of physiological variables after hospitalization and, with study 2 we expect to find and effective and accessible virtual RP with individualized prescription, thus increasing the access to PR benefits such as improvements in functional capacity and quality of life of patients after COVID-19 infection.",2021,2023,Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C15855,20/14357-1,Mathematical models describing the COVID-19 pandemic,"The objective of this project is to propose new mathematical models to describe the COVID-19 pandemic, which will be valid for different regions of the world, at different territorial levels (countries, states, municipalities). An automatic methodology to calibrate the models, without requiring intervention from experts, will be proposed, such that the analysis could be performed even in regions with limited financial resources. New techniques for trend analysis will be developed, in order to provide relevant information to health authorities. Predictions will be performed concerning the future behavior of the pandemic, with special focus on the number of nursing beds and intensive care units (ICUs). The models to be proposed will be such that they may be generalized to other epidemics in the future. The analyses will use information from the websites of the European Center for Disease Prevention and Control (ECDC), Johns Hopkins University, São Paulo State Department of Health and Brasil.io Project. The results will be assessed through theoretical analyses, comparisons with similar results from the literature and, mainly, comparison between simulated and real results. Articles will be published in journals and conferences. At least two master's theses will be supervised.",2021,2023,Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Data Management and Data Sharing,,,Brazil,Brazil,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2021 +C15856,21/02608-2,Construction and selection of a library of scFv monoclonal antibodies against SARS-CoV-2 spike protein by phage display technology,"Antibodies against SARS-CoV-2 are critical molecules of the efforts to understand and fight the COVID-19 Pandemic. They play a central role in clearing the virus from infected patients. They are key reagents of rapid diagnostics. They are first-line treatments for hospitalized COVID-19 patients and are the main objective of COVID-19 vaccine development. The vaccines and therapeutic antibodies currently available were developed from the spike protein of SARS-CoV-2 variants circulated during the early stages of the Pandemic in 2020. With the emergence of new variants from mutations in the spike protein receptor (RBD) binding site, concerns have been raised about the impairment of neutralizing antibody responses and vaccination programs' effectiveness. In this context, this proposal's objective is the generation of monoclonal antibodies against the Brazilian variant P.1 spike protein for immunotherapy and prevention of COVID-19. So far, there are no antibodies against this new variant, and the development of a national input to combat the Pandemic is significant. The antibodies will be selected from a library of antibody fragments in the scFv format and selected against the spike protein using Phage display technology. After selection, the most reactive antibodies will be produced in the scFv-Fc form in HEK-293 mammalian cells using technology and knowledge acquired during a post-doctoral internship carried out by the applicant in Germany - Stuttgart University. Subsequently, these antibodies' functional characterization will be carried out, for example, the analysis of the antibodies' neutralizing potential to the virus and in silico analyzes to characterize the antigen-antibody interaction. This study will provide a database of neutralizing antibodies for SARS-CoV-2 that can contribute to the development of effective immunotherapies in the clinical management of patients with COVID-19 in the future. This proposal is part of the Institutional Research Development Plan of the Instituto Adolfo Lutz (PDIP) (Process: 17/50333-7)",2021,2021,"Instituto Adolfo Lutz (IAL), Coordenadoria de Controle de Doenças (CCD), Secretaria da Saúde (São Paulo - Estado)",,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas | Europe,Data Management and Data Sharing,,,Brazil,Brazil | Germany,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15857,21/05698-2,Development of a T-cell-inducing vaccine against SARS-CoV-2 infection,,2021,2022,N/A,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,,Americas,,,,,Brazil,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C15858,20/15323-3,Disregulation of inflammasome' activation in neutrophil and endothelium in response to SARS-Cov-2 and contribution to severe COVID-19,"The COVID 19 pandemic is caused by the emerging virus SARS-COV-2 and is responsible for more than 1 million deaths worldwide. The immunopathology of COVID-19 is characterized by a systemic inflammation with significant hematological changes such as neutrophilia and lymphopenia and an exacerbated production of inflammatory cytokines responsible for a viral sepsis in the most severe cases of the disease. IL 1² and IL 18 stand out among the cytokines markedly deregulated during the infection by SARS-COV-2 and both are produced with inflammasome activation The inflammasome is a multiprotein complex activated in response to several PAMPs and DAMPs pathogen and damage associated molecular pattern which are recognized by different cytosolic receptors as NLRP3 the most well known and studied. In the context of SARS COV 2 infection, recent data point to a direct NLRP3 activation in macrophages, however little is known about a possible activation of NLRP3 in other cell types such as neutrophils or endothelial cells. Recent studies indicate that both cells are capable of activating the NLRP3 inflammasome and are involved in the pathogenesis of several infectious diseases, inflammatory and coagulopathies similar to COVID-19 manifestations. In this sense, we intend to investigate the profile of activation of NLRP3 inflammasome complex in neutrophils and endothelial cells with a focus on the severity of the disease as well as the role of inflammasome genetics in the interindividual variability of clinical manifestation, enabling not only a better understanding of the disease's immunopathogenesis but also the identification of possible therapeutic targets helping to face the pandemic.",2021,2023,Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP),,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease susceptibility | Disease pathogenesis",2021 +C15859,21/05428-5,Development and standardization of experimental models of SARS-CoV-2 virus infection,"COVID-19, the disease caused by the SARS-CoV-2 virus, is a major cause of public health concern worldwide. Scientists in basic and clinical areas around the world are having significant effects on the understanding of the pathophysiology and the investigation or effect of drugs with antiviral action and the repositioning of drugs that perform anti-inflammatory action, and there is still no medicine or clinical treatment for patients a COVID-19. However, it is known that progressive respiratory failure causes damage caused by alveolar cells, is caused by viral replication, and excessive local inflammation, is one of the major obstacles to the recovery of critically ill patients with COVID-19. In this sense, the host's defense against infections depends not only on the mechanisms of immune resistance but also on the organism's ability to tolerate the damage that a determined individual promotes. An amphiregulin (AREG) is a central factor that promotes repair and restoration of tissue integrity after tissue damage associated with inflammation. AREG-deficient animals have a substantial impairment of the ability to restore lung function in infection models. In addition, the administration of recombinant AREG enhances the tissue repair process after tissue damage resulting from excessive inflation. Our working hypothesis is that AREG plays a crucial role in repairing and restoring the integrity of lung tissue during a COVID-19 and that treatment with AREG is recombinant during the patients' recovery period. Thus, we propose in the present project to standardize the experimental model of Sars-CoV-2 infection and to investigate the role of AREG in the pathophysiology of COVID-19",2021,2022,Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP),,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Disease pathogenesis,2021 +C15860,20/15847-2,Impact of immunosenescence on in vitro response of B lymphocytes of individuals vaccinated against COVID-19: influence of smoking and chronic obstructive pulmonary disease,"The fact that COVID-19 pandemia has led to an unprecedented, worldwide effort to develop a vaccine able to confer protection to a large and heterogeneous population, gave rise to the reemergence of the issue of vaccination of elderly and those bearing chronic diseases. While these populations show enhanced susceptibility to the severe forms of the COVID-19, they also tend to develop weaker vaccine responses compared with youngs and adults in general. Aged people are immunologically characterized for presenting immunosenescence. This condition refers to a state defined by robust measures of immune parameters (biomarkers) that are different in younger and older individuals that have been associated with detrimental clinical outcome (e.g. mortality, frailty, poor response to vaccination). Individuals suffering from chronic inflammatory diseases. e.g., COPD patients also develop a phenotype called accelerated immunosenescence. Several aspects of immunosenescence have been investigated in the last two decades, mostly dealing with the T lymphocyte compartment. Information regarding alterations of the B lymphocyte compartment linked to immunosenescence are less well understood and less well established, as can be exemplified by the role of B lymphocytes in the poorer vaccine responses of the elderly. Therefore, this project aims to investigate the B lymphocyte response and production of specific antibodies to SARS-CoV-2 proteins after vaccination against COVID-19. Peripheral blood mononuclear cells from healthy aged individuals (e 60 y-o), patients with COPD, aged smokers but without pulmonary impairment compatible with COPD, will be compared with PBMC from young adults (e 35 y-o). PBMC cultures will be submitted to several analyses: phenotyping assays (flow cytometry) to determine the B lymphocyte subpopulations and the expression of surface and intracellular functional molecules, assays for purifying B lymphocyte population followed by in vitro expansion of these cells, and then exposure to specific viral proteins to evaluate the capacity of clonal expansion, specific antibody production and pro/anti-inflammatory cytokines secretion, as well as testing the B lymphocyte culture supernatants in a SARS-CoV-2 neutralization assay. Some features of the T-cell responses will also be assessed, such as Th patterns, cytokines and immunophenotyping. We expect, with these experiments, to collect relevant data aiming at better characterizing B lymphocyte responses to the vaccine in the healthy aged and in the aged with comorbidities. This knowledge is crucial for the design of better vaccine candidates in this specific population: beyond the well-known effects of immunosenescence on the T-cell compartment, information regarding B lymphocyte dysfunctions may uncover novel mechanisms that impair vaccines response, particularly regarding the amount and quality of the antibody production.",2021,2023,Faculdade de Medicina (FM). Universidade de São Paulo (USP),,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other | Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C15861,20/12141-1,Evidence-based design in the COVID-19 pandemic control context,"The architectural design of Hospitals can contribute to the humanization of care and to combat the transmission of pathogens through strategies of natural ventilation and social segregation and distancing in areas of potential agglomeration. The occurrence of epidemics and pandemics highlights the importance of research related to the physical space, aimed at establishing design guidelines with an emphasis on preventing contamination, while valuing the user's sense of security and the humanization of hospital spaces. The proposed research addresses the physical space of HU-UFSCar, modeling virtually three scenarios: i) organization of the main spaces and flows prior to the pandemic and ventilation CFD, referring to the original project; ii) the spatial adjustments implemented during the pandemic and the current natural ventilation CFD model; and iii) simulate spatial organization alternatives, flows and natural ventilation schemes. The simulated scenarios will be evaluated through interviews with patient users to discuss the sense of security in relation to the hospital stay; interviews with the hospital health professionals about the perception of the effectiveness of alternatives regarding biological protection related to contamination by infectious diseases; evaluation through mathematical CFD models of the efficiency of natural ventilation. Once the results and evidence are generated, it is intended to organize design guidelines for hospitals to be considered permanently and guidelines to be implemented in pandemic scenarios.",2021,2023,Instituto de Arquitetura e Urbanismo de São Carlos (IAU). Universidade de São Paulo (USP),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2021 +C15862,21/05661-1,Viral characterization of Brazilian isolates of SARS-CoV-2 and study of sequence variation and evolutionary patterns of Spike protein to evaluate potential vaccine escape by target or epitope modification,"This research proposal consists of a ""spin-off"" project based on volunteer samples of the Oxford-UNIFESP ChAdOx1 nCoV-19 vaccine trial. The proposal will involve the 1,000 volunteer samples, and corresponding time points, to primarily establish a collection of samples for the whole academic community of the São Paulo State. This collection will be stored in the Biobank stablished at UNIFESP, as is stated in current legislation. In addition, the samples stored in the Biobank will be used to perform analysis of these samples that do not overlap with the ""Primary and Secondary Outcome Measures"" as described in the clinical trial documentation available in ClinicalTrials.gov (National Institutes of Health, ID NCT04400838). This project will be coordinated by Prof. Luiz Mario Janini and will include a team of principal investigators in different areas pertaining to the specific objectives and research track record at FAPESP. The objectives of this project are: (1) store and provide all samples obtained from volunteers before and after vaccination at UNIFESP's Biobank. This Biobank was built in accordance with legal procedures, with the objective of correctly storing and making samples available to the entire scientific community of the State of São Paulo, nationally and internationally, (2) to evaluate the neutralizing capacity of sera from vaccinated subjects against Brazilian-specific circulating SARS-CoV-2 strains and other Brazilian specific strains of coronavirus for assessment of cross immunity, (3) to characterize Brazilian specific isolates of SARS-CoV-2 and study the sequence variation and evolutionary patterns of the SARS-CoV-2 Spike protein in to assess the potential of vaccine escape by modification of the target or epitopes, (4) to generate and analyze cytokine profiles of serum from volunteers before and after vaccination to evaluate the inflammatory response and associated effects, (5) To analyze and compare the blood transcriptomes of volunteers, by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to evaluate the impact of the vaccine on differential gene expression levels and assess 3 the individual variation in genetic response to the vaccine and (6) To analyze the whole blood secretome profiles of volunteers, before and after vaccination, to assess the predominant type of immune response and priming by another coronavirus.",2021,2023,Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +C15863,21/06699-2,Exploring the molecular basis of SARS-CoV-2 infection in preclinical neural models,"There is still little understanding of the molecular mechanisms of SARS-CoV-2 infection, especially in the central nervous system (CNS). This makes it difficult to halt the rapid spread of the virus, which has taken on pandemic dimensions, leading many countries, including Brazil, to declare a state of public calamity. There is evidence that SARS-CoV2 is hosted not only in the respiratory tract but that it can also infect the CNS, induce neurological changes and symptoms, such as headache, nausea and vomiting. In early 2003, samples from SARS-CoV-infected patients demonstrated the presence of viral particles in the brain, mainly in neurons. The presence of SARS-CoV was also observed in the brain of infected animal preclinical models, and the number of positive samples for SARS-CoV increased during the course of infection, with prevalence in the hippocampus. In this project we will investigate, at the protein and metabolite level, the influence of SARS-CoV-2 on human in vitro models. We will generate neurons and astrocytes derived from neural stem cells. These cells, infected, uninfected and eventually treated with potential anti-viral drugs, will have their proteomes and metabolomes investigated by large-scale mass spectrometry. We hope to unveil biochemical pathways and potential therapeutic targets associated with SARS-CoV-2 infection, which will serve as a basis for new treatments. The data generated here may compose a framework of information about the mode of infection by coronaviruses.",2021,2022,Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP),,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2021 +C15864,20/10711-5,Study of the mechanisms involved in the modulation of the renin-angiotensin System in the three-dimensional bronchioles from a 3D human co-culture infected by SARS-CoV-2 to produce inflammatory mediators,"An outbreak of new coronavirus-related pneumonia was identified in December 2019, and has expanded rapidly, with cases now confirmed in more than 211 countries or more areas. This constant transmission of a new SARS-CoV-2 and its ability to spread from human to human led scientists to develop new approaches to the treatment of COVID-19. One of the main targets of this virus is to drastically alter the host's immune system, causing an exacerbated release of cytokines and chemokines leading to changes in the immune response and damaging the airways. The input receptor for this SARS-CoV-2 is that of the angiotensin-converting enzyme 2 (ACE2), involved in the renin-angiotensin system (RAS) and the main protein bound by the virus to this receptor is protein S. Several drugs are being used for reducing the symptoms of this disease and its side effects, however, none of them have been effective in reducing the damage to the host more quickly. Thus, the objective of the present study will be to evaluate the mechanisms involved in RAS modulation by three-dimensional bronchiole co-culture 3D infected by SARS-CoV-2 for production of inflammatory mediators in the presence of RAS axis inhibitors and inhibitors of protein S of SARS-CoV-2. The discovery of new mechanisms to modulate the immune response could be a new pharmacological tool to contain the infection and could be of great advancement for the treatment of inflammatory manifestations of this disease that affects the world population.",2021,2023,Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba,,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis",2021 +C15865,20/14172-1,"The impact of the new SARS-CoV-2 coronavirus on skeletal muscle: morphological, biochemical and functional analysis","COVID-19 pandemic, a disease caused by the new coronavirus SARS-CoV-2, has been drastically affecting the lifestyle of millions of people in the past few months. Studies have shown that COVID-19 is a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and damage to skeletal muscles. These symptoms can persist even after the infection ends, perduring for months and impacting the daily lives of individuals who, in theory, should have fully recovered. Some studies have indicated that the muscle weakness observed in COVID-19-positive individuals could be an effect of the deregulated immune response (""cytokine storm"") that occurs during the course of the disease, and several pro-inflammatory interleukins have been found at high levels in the serum of studied patients. However, little is known about the effect of SARS-CoV-2 on skeletal muscles, especially of individuals who did not require hospitalization and/or ventilatory support. Therefore, we will analyze the contractile properties of fibers and myofibrils of skeletal muscles from individuals who presented the mild-to-moderate forms of COVID-19 and recovered from it, as well as the content of sarcomeric proteins and cytokines, relating this content to the possible effects of a deregulated immune response. We aim to contribute to a better understanding of the effects of COVID-19 on the musculoskeletal system.",2021,2023,Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C15866,20/16655-0,Prevalence of SARS-CoV-2 RNA and antibodies among Head and Neck cancer from Italy and Brazil: a case study embedded in the HEADLAcE consortium,"Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), the cause of COVID 19, has been declared a pandemic by the World Health Organization. The majority of severe cases and mortality occur in individuals with underlying health conditions. Still, how these risks apply to patients with cancer remains unclear. Very preliminary study conducted in cancer patients in China, indicates that patients with cancer and cancer survivors constitute a critical at-risk population for SARS-CoV-2. Furthermore, these individuals had a significant higher risk of severe events (admission to the intensive care unit with requirement of invasive ventilation or death) compared with those without cancer. An effective approach to diminish the ongoing pandemic requires a comprehensive understanding of the immune responses against SARS-CoV-2. Testing for this virus should be considered to better define the patient/procedure level of risk. In addition to screening, knowledge of exposure to SARS-CoV-2 can contribute to understanding the epidemiology of COVID-19 in cancer patients, in particular among those with head and neck cancers (HNC).We now have an opportunity to extend our goals with this project supported by the EULAC-HEALTH CONSORTIUM and the FAPESP to address a timely question about the exposure to SARS-CoV-2.",2021,2023,Faculdade de Medicina - Universidade de SÇ?o Paulo (USP),,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas | Europe,Americas | Europe,,,,Italy | Brazil,Italy | Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2021 +C15867,20/13148-0,Evaluation of ATP-adenosine axis in lymphocytes in SARS-CoV-2 infection,"Adenosine triphosphate (ATP) is a predominantly intracellular molecule that can be released to the extracellular space during cellular activation, tissue stress or damage. Out of the cell, ATP can play a crucial role in immune responses and inflammation. Extracellular ATP can be rapidly converted to ADP, AMP and adenosine by ectonucleotidases, such as CD39 and CD73 that are present in the cell membrane. Adenosine, in turn, can induce anti-inflammatory responses by inducing cyclic AMP. Changes in ATP metabolism and signaling have already been observed in cases of viral infection with chronic immunoactivation, such as HIV, and our preliminary data suggest that a similar scenario could be occurring in the infection with the new coronavirus that causes COVID-19. This infection can lead to a high production of pro-inflammatory cytokines, a phenomenon known as cytokine storm. Analyzing CD39 and CD73 expression in leukocytes of COVID-19 patients, with moderate and severe clinical forms of the disease, from the Clinics Hospital of São Paulo we observed a reduction in the frequency of neutrophils and CD8+ T cells expressing CD73. Besides that, we detected a reduction of CD19+CD39+CD73+ cells in peripheral blood of patients with severe COVID-19, suggesting that extracellular ATP metabolism in B cells can be altered in the disease. Therefore, we believe that the reduction of CD19+CD39+CD73+ cells could be associated to the pro-inflammatory profile observed in COVID-19 patients. To test our hypothesis, CD19+ B cells will be isolated from COVID-19 patients and healthy controls and ATP metabolism into adenosine will be evaluated by high performance liquid chromatography (HPLC). The immunomodulatory effects of adenosine will be tested in vitro in B cell and mononuclear cells cultures. The immunomodulatory role of B cells from COVID-19 patients in autologous T cell activation and proliferation will also be investigated. Finally, we will also verify the expression of other ectonucleotidases and adenosine receptors in COVID-19 patients as well as the serum levels of adenosine. These results may help to understand the mechanisms involved in COVID-19 pathogenesis and will indicate possible strategies for therapeutic interventions.",2021,2023,Faculdade de Medicina (FM). Universidade de São Paulo (USP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +C15868,20/10414-0,Association between ARA:EPA/DHA ratio and inflammation in the plasma of patients with COVID 19,"Studies have shown that beyond the onset symptoms of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill patients. Taking into account that there are still no approved drugs or vaccines, the potential effect of dietary supplements to improve the patient's recovery can be considered. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate the recovery of patients requiring hospitalization or/and ventilatory support. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins, contributing to inflammation resolution. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. In order to check if EPA+ DHA could be a strategy to act as adjuvant to treat patients infected with SARS-Cov-2, our objective is to evaluate the relation between ARA:EPA+DHA ratio, that is a biomarker of omega-3 fatty acids consumption, and the prognosis of patients with COVID-19. Our hypothesis is that patients that present a lower ARA:EPA+DHA ratio present higher concentration of SPMs and a general better recovery when compared with patients that present a higher ARA:EPA+DHA ratio. It will be collected blood samples from about 180 patients that are being recruited by other experimental study (FAPESP 2020/05752-4). The samples will be kept at -80oC until the analysis. Fatty acids profile, cytokines, prostagladins and oxidative markers will be analyzed in the samples. A multivariate statistical approach will be applied to correlate data obtained from the patient plasma analysis with the patient clinical outcomes",2021,2023,Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C15869,20/13370-4,COVID-19-induced fibrosing interstitial pneumonitis,"Fibrosing interstitial pneumonitis (FIP) can be defined as an attempt to repair the injured lung tissue, with some or extensive extracellular matrix deposition, causing lung parenchyma disarrangement and septal thickening. The regulatory mechanisms involved in fibrogenesis are complex and with several molecules. FIP can be the common end result to many different lung diseases (for instance idiopathic pulmonary fibrosis) or be related to chronic viral inflammations, such as the new 2019 Coronavirus Disease (COVID-19), caused by the SARS-CoV-2 virus. Some patients infected with this disease develop the acute respiratory distress syndrome, which is characterized by acute and diffuse inflammatory damage to the pulmonary alveoli. Histopathologically, this condition is known as diffuse alveolar damage, which consists of permanent damage to epithelial and endothelial cells with consequent hyaline membrane formation. In addition, this condition is characterized by exacerbated myofibroblastic proliferation with subsequent extracellular matrix deposition, resulting in parenchyma remodeling and future FIP, which can frequently be the COVID-19 outcome. Thus, fibroblasts and myofibroblasts are the main factors within the fibrogenesis process and the comprehension of regulatory mechanisms and the genes involved in this process are essential for its complete understanding. At the same time, this knowledge translationally integrated with clinical-radio-laboratory profile could determine the patients' phenotype in relation to the stage of fibrosing interstitial pneumonitis . With this in mind and due to the COVID-19 great socioeconomic impact, the transcriptomic profile of infected lung tissue together with the characterization of fibrotic pulmonary microenvironment will enable the identification of a wide range of potential biomarkers that may predict fibrosing interstitial pneumonitis in these patients. Therefore, the main purpose of this project is to determine the molecular profile and potential biomarker of pulmonary myofibroblastic microenvironment post-COVID19, characterizing patients in different phenotypes according to the PIF degree, after translational screening of COVID-19 candidates through minimally invasive autopsy.",2021,2023,Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2021 +C15870,20/10087-0,"Prospective study of a cohort of patients discharged after severe acute respiratory syndrome and COVID-19: epidemiological, clinical and functional aspects","The medium and long-term clinical outcomes and consequences of COVID-19 are still unclear. Knowing the possible clinical and functional sequela in patients who had pulmonary infections by SARS-Cov2 and who needed hospitalization and oxygen therapy can contribute to a better understanding of the evolution and impact of the disease, as well as to the management of these conditions. This project has as main objectives 1) assessment of incidence, etiology, and indicators of opportunity in cases of severe acute respiratory syndrome(SARS), and 2) assessment, in cases of confirmed COVID-19, of clinical, epidemiological, functional, radiological, and quality of life parameters related to acute manifestations; in patients with SARS and COVID-19 we aimed also 3) to evaluate the functional, radiological and quality of life in the medium and long term, and 4) to evaluate and to compare the effectiveness of a pulmonary telerehabilitation program in the exclusively remote versus face-to-face and remote modality in patients with respiratory dysfunction after hospitalization for COVID-19pneumonia. This is a prospective cohort of adult participants hospitalized with SARS consecutively at the Hospital de Clínicas (HC) of University of Campinas (Unicamp), from May1st, 2020 to May 1st, 2021. It is estimated that 600 cases of SARS will be included, of which 150 are confirmed for COVID-19. For objective 4, patients will be randomized to one of two groups, PTRP exclusively remote (GR-R) versus remote and face-to-face (GR-P), and it is intended to include 50 patients. Patients will be followed during hospitalization until discharge, transfer or death. After discharge, patients with SARS and COVID-19 will be followed up on an outpatient basis until the 12th month, with medical and physiotherapeutic evaluations, as well as laboratory, functional, and imaging tests. Persistently symptomatic patients will be invited to participate in the PTRP lasting 12 weeks, with assessment of functional capacity and quality of life before and at the end of the program. Clinical and therapeutic decisions will be made according to Unicamp's HC assistance protocol for COVID-19. Persistent symptomatic patients will be invited to participate in a Pulmonary Telerehabilitation Program. Primary outcomes will2be death, use of mechanical ventilation, functional respiratory dysfunction and quality of life. Secondary outcomes will be days in the ICU, days on mechanical ventilation, occurrence of infections related to health care, occurrence of pulmonary thromboembolism, readmission byCOVID-19, functional capacity. For objective 4, the outcomes analyzed will be functional capacity and quality of life. The data will be stored on the Red-Cap platform, a free platform for collecting and managing research data and clinical protocols whose function is to build and manage research and databases securely. The statistical analysis will be performed using the SPSS statistics package, Windows version 17.0.",2021,2023,Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP),,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,Digital Health,,,Brazil,Brazil,Clinical characterisation and management,"Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +C15871,21/07121-4,"Problematizing negationism: COVID-19 pandemic, democracy, and human rights","The project aims to problematize, catalog, and understand the discourse of negationism concerning the COVID-19 pandemic, democracy, and human rights, understanding it as an essential element of current political culture and socially implanted authoritarianism close relationship with social networks. Based on the hypothesis of nuances and specificities of negationism(historical, scientific, environmental, and racial), it is intended to understand how the theme has been presented in the media (newspapers) and, in contrast, how it is conveyed in social networks, with an emphasis on content analysis of channels of the Telegram messaging application. The research methodology will operationalize the collection and analysis of big data on two fronts: (i) through a web crawler that captures news that mentions denial; and (ii) collecting the content of Telegram channels, and in both procedures, there is the identification of keywords and thematic analysis. Finally, it is expected to comparatively analyze the content, showing how the negationist discourse imposes itself, its targets, arguments, and dissemination methods.",2021,2022,"Faculdade de Filosofia, Letras e Ciências Humanas (FFLCH). Universidade de São Paulo (USP)",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Other secondary impacts,2021 +C15872,21/06054-1,"Search for antiviral drugs, targeting RNA-dependent RNA polymerases (RdRp) from the Alphavirus Chikungunya (NSP4) and Beta-Coronavirus SARS-CoV-2 (NSP12)","Emerging and reemerging viruses will always constitute a threat and a challenge to global public health. Despite the recent COVID-19 pandemic highlight, the emergence of diseases caused by viral agents is not a new phenomenon. In Brazil, for at least 30 years, there has been the emergence and re-emergence of viral diseases, caused mainly by arboviruses, such as the Chikungunya epidemic that began in 2014 and is still ongoing. The COVID-19 pandemic, which began in December 2019, posed additional challenges to scientific research and health services. In Brazil, there were records of a significant increase in cases of Chikungunya, Dengue and Zika in the first half of 2020. This epidemiological scenario, of simultaneous viral infections, represents a risk of mistaken health actions, in addition to the possibility of coinfections. Therefore, efforts in basic research, in search of vaccines and antiviral agents, must happen quickly, attacking different viruses simultaneously. Thus, has as its main objective the use of structural biology as a tool in the search for molecules that can help in the development of specific antiviral drugs targeting RNA-dependent RNA polymerases (RdRp), respectively from CHIKV (NSP4) and SARS -CoV-2 (NSP12). For this, it will be necessary to produce these enzymes in recombinant form, which will then be explored through biophysical and biochemical strategies for the identification and/or planning of inhibitors through the Structure-Based Drug Discovery (SBDD) and Fragment Based Drug Discovery (FBDD) methods, aimed at discovering potential drug candidate that can be used in pre-clinical studies against the Chikungunya Fever and COVID-19. This project is linked to the FAPESP's CIBFar/CEPID project.",2021,2023,Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15873,21/08468-8,Development of VLPs-based vaccines against SARS-CoV-2 and other human Coronaviruses,"SARS-CoV-2 vaccines must be one step ahead of the rapid evolution of the virus. Therefore immunogenic and flexible vaccine platforms are needed. Variants of concern (VOCs) that continually emerge with an unprecedented spread of the virus have already significantly increased the transmissibility and severity of COVID-19 and affected the efficacy and effectiveness of vaccines and vaccination worldwide, being no different in Brazil. Moreover, the recent pandemic is not the first and will not be the last one caused by zoonotic Coronaviruses in this century, as seen with SARS and MERS. Virus-Like Particles (VLPs) are a highly versatile and already consolidated vaccine platform against other viruses, such as HBC and HPV. And the recent approval and success of mRNA vaccines against COVID-19 is also exciting since this technology is versatile and easily adaptable against new epidemiologic threats. This project will develop three VLPs-based vaccines: two composed of QB-VLPs associated with mRNA against SARS-CoV-2 and Pancoronavirus, respectively, and another homologous VLPs comprising the S, M, E, and N proteins from SARS-CoV-2. The use of novel vaccines that use mRNA associated with VLPs represents a promising way of fighting the COVID-19 pandemic, new VOCs, and future Coronaviruses outbreaks.",2021,2025,Gustavo Cabral de Miranda,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C15874,21/06036-3,"Characterization of non-structural proteins Nsp13 and Nsp15 from SARS-CoV-2, and investigation of bioactive compounds with potential antiviral action","Emerging and reemerging viruses will always constitute a threat and a challenge to global public health. The emergence of a new type of coronavirus (SARS-CoV-2), in December 2019, generated an epidemic that has lasted until now and has already resulted in more than 174,418,411 cases worldwide, with 17,130,234 of them in the Brazilian territory. Statistics still show about 3,757,791 deaths registered worldwide, with 479,811 of them in Brazil (early June/2021). Despite the efforts used to combat this pandemic and past outbreaks (SARS and MERS), considering the development of antivirals, it is known that no drug has proven effective in clinical trials. Therefore, this project aims to use the structural information of the non-structural proteins Nsp13 - helicase and Nsp15- endoribonuclease of SARS-CoV-2 to help in the search for molecules that can help in the development of specific antiviral drugs for this virus. In this context, the production and characterization of these proteins, which are involved in the process of viral replication, will be conducted and from these samples we intend to use a combination of biophysical and biochemical techniques to identify new antiviral candidates using the Structure-Based Drug Discovery (SBDD) methods. In this way, we aim to obtain a potential drug candidate, which can be used in pre-clinical tests. This project is linked to the project 2020/04602-9 approved at the FAPESP COVID-19 call for proposals.",2021,2022,Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C15875,20/04826-4,"Evaluation of blood levels of cytokines, caspase-1 and NETs in patients with moderate and severe forms of COVID-19 treated with standard therapy plus placebo or colchicine","Introduction. 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major health problem worldwide. The most frequent clinical manifestations include fever, cough, fatigue, sputum, dyspnoea, pain in the oropharynx and headache. Elderly and individuals with chronic diseases are the group most at risk for moderate and severe forms of the disease and for the development of acute respiratory distress syndrome (ARDS). The diagnosis is based on epidemiology, presence of fever and respiratory symptoms, image examination of the lungs (infiltrated in ground glass on computed tomography) and detection of viral RNA by RT-PCR (polymerase chain reaction with reverse transcriptase) in secretions of the airways. There is no specific treatment for COVID-19 disease, which is supportive when patients have pneumonia requiring hospitalization. We showed, in a double-blind, placebo-controlled clinical trial, that the use of colchicine in cases of moderate and severe COVID-19 led to a reduction in the duration of supplemental oxygen therapy and a reduction in the length of hospital stay, without the occurrence of serious adverse events. Goals. To quantify cytokines, caspase-1 and NET products in the blood of patients with COVID-19 at admission and during evolution. To assess whether there is a correlation between blood levels of cytokines and NETs and general clinical and laboratory parameters in patients with COVID-19 treated or not with colchicine. To evaluate whether the quantification of cytokines and/or NETs can be a predictor of response to treatment with colchicine in the moderate and severe forms of COVID-19. Patients and methods. We will proceed with the quantification of cytokines, caspase-1 and NETs in biological material obtained from 100 participants in a randomized clinical study, with 1:1 allocation in two groups: standard treatment plus placebo (control group, n=50) versus standard treatment plus colchicine (colchicine group, n=50). Patients in the colchicine group will receive medication at a dose of 0.015-0.033 mg / kg / day for 5 days, followed by 0.012-0.020 mg / kg / day for 5 days, for a total of 10 days. The evaluation of cytokines, extracellular caspases and NETs will be performed on admission and on days 2 or 3, 5, 7, 10 and 14 of hospitalization.",2021,2023,Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2021 +C15876,21/05316-2,Environmental genomic surveillance as a tool to detect and quantify SARS-CoV-2 variants in Brazil,"We do not know which variants of SARS-CoV-2 occur today in Brazil, an even worse situation in the different regions of the country. The little that is known is due to the study of patients with classic or suspected symptoms for COVID-19, whose material follows to determine the viral variant after diagnosis, which in the best scenario is determined several days after the onset of symptoms. In this way, this project seeks to assist in accelerating the discovery and determination of variants of greater local importance. The rationale is that determining variants found in environmental samples may be able to anticipate samples that will have greater clinical relevance in the near future. Likewise, we do not know whether current viral variants will remain with relevant frequencies after vaccination, whether some will grow in prevalence after massive vaccination, or whether new variants will emerge after vaccination, scenarios that may indicate some level of resistance to immunization. In the same way, we will have a faster method that can detect the entry of variants on the rise in other countries of the world. This is a pilot project, involving six cities, half in the State of Paraná and half in the State of São Paulo. In these cities, we will evaluate samples of the hospital and non-hospital environments. If successful and informative, we will apply to expand the project to the whole country. Only environmental collections will be obtained, with no collections from individuals. The data will be analyzed quickly and disseminated to the competent health authorities.",2021,2022,A C Camargo Cancer Center. Fundação Antonio Prudente (FAP),,Viruses | Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2021 +C15877,20/10082-8,How did large companies based in Brazil capture disperse knowledge to feed their corporate risk management and corporate crisis management programs in the COVID-19 pandemic and post-pandemic?,"Objective: The scale of Covid-19 pandemic required from companies an additional ability to gather dispersed information, adapt and respond. Therefore, the objective of this study will be to understand how, in the context of the Covid-19 pandemic, large multinational corporations installed in Brazil, captured dispersed knowledge and used them to feed their Enterprise Risk Management and Corporate Crisis Management programs. Design/methodology/approach: Based on the conceptual triad formed by Knowledge Management, Corporate Risk Management and Corporate Crisis Management, a qualitative research will be developed, using the multiple case study method (MILES et al., 2014), and using precepts of Design Science Research (ROMME, 2003) to achieve the proposed objective. For that, senior executives from five large multinational companies installed in Brazil will be interviewed. Their responses will be submitted to the content analysis method (BARDIN, 2010) in order to achieve a deep understanding of the context experienced by organizations during and after the Covid-19 pandemic. Theoretical implications: The research will be supported by the theories of Transactive Memory (WEGNER, 1986), Spiral of Knowledge (NONAKA; TAKEUCHI, 1995), Business Environment (OLIVA, 2016), Barriers to Knowledge Management (OLIVA, 2014). At the end, a new Dispersed Knowledge Management model will be proposed, aimed at protecting organizations. Practical implications: The new Dispersed Knowledge Management model will have a high potential for practical application in order to help organizations and their managers in future crises. Originality/value: There are no previous researches which have studied the conceptual triad aforementioned in an integrated way, nor that, based on them, have developed research on Dispersed Knowledge Management in pandemic contexts, which will allow to obtain a deep knowledge about the subject and develop knowledge with potential to expand the state of the art in Dispersed Knowledge Management.",2021,2023,"Faculdade de Economia, Administração e Contabilidade (FEA). Universidade de São Paulo (USP)",,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C15878,21/03328-3,Development of new methodologies and machine intelligence-based technological solutions for digital image segmentation and COVID-19 pandemic response,"This project comprises two distinct research branches: Digital Image Segmentation and Data-Driven Epidemiological Modeling against COVID-19. Our proposal aims at combining theoretical as well as technical advancements as a solution for different applications in the field of Computational Intelligence, whose previous results have been published in high-quality refereed publications such as IEEE CVPR, IEEE TIP and IEEE TPAMI. Considering the image segmentation topic, new concepts and clustering strategies for graphs derived from digital images will be investigated. Also, techniques inspired on spectral cutting and energy minimization rules will be studied, as well as deep learning strategies and graph differential operators in the image processing context, including eigenvalues and eigenfunctions, thus allowing us to design new methodologies and theoretical results. Concerning the Covid-19 research, this proposal extends the ongoing actions and researches now being carried out against the new coronavirus in Brazil, which range from digital inclusion of the Brazilian society to new studies of mathematical models for forecasting coronavirus-related data in the country",2021,2023,Universidade Estadual Paulista (UNESP). Campus de Rosana,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Epidemiological studies,Disease surveillance & mapping,2021 +C15879,20/07730-8,Impact of social distancing measures in the COVID-19 pandemic on the mental health of adolescents belonging to a birth cohort,"The emergence of the new SARS-CoV-2 coronavirus represents a global public health challenge and Brazil is now considered the new epicenter of the pandemic. With the unavailability of treatments and vaccine, the only existing strategies to stop the infection spreading adopted by several Brazilian states were social distancing or lockdown. In addition to the inherent tensions of the pandemic and the concern for one's own health and that of loved ones, confinement at home can have severe impacts on individuals´ mental health due to the reduction of social interactions and the uncertainty of the maintenance of the income. Children and adolescents represent a particularly vulnerable group to the negative consequences of the pandemic and social isolation, and the little existing evidence suggests increased risks of developing depressive, anxious and post-traumatic stress symptoms. The project aims to assess the impact of social distancing measures during the Covid-19 pandemic on the mental health of 15-year-old adolescents belonging to the 2004 Pelotas Birth Cohort. In November 2019, the seventh follow-up of the cohort began. On 23rd March 2020, social distancing measures were decreed in the state of Rio Grande do Sul and the follow-up was suspended, at which point 1950 interviews had been completed. In the present project, we aimed to reevaluate the mental health of those 1950 adolescents after social distancing measures are suspended and to compare the frequency of mental health outcomes before and after these measures. New and relevant data will be produced regarding the impacts of social distancing measures on adolescent's mental health, which will subsidize actions to alleviate its consequences in later life.",2021,2023,Alicia Matijasevich Manitto,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C15880,20/15947-7,Mapping and mechanistic characterization of the interaction of the human HspA5 (BiP/Grp78/erHsp70) protein with the human Hep1 co-chaperone and with the Spike protein of the SARS-CoV-2 Coronavirus,"The 70 kDa Heat shock proteins (Hsp70) are molecular chaperones that act in the control of cell protein quality. They are monomeric, ubiquitous, highly conserved proteins and are composed of a Nucleotide Binding Domain (NBD) and a Peptide-substrate Binding Domain (PBD). To direct their functional cycle, Hsp70 rely on the help of adenosine nucleotides and auxiliary proteins: co-chaperones. HspA5 (Grp78/BiP/erHsp70) is human Hsp70 isoform that resides mainly in the Endoplasmic Reticulum (ER) and plays several essential cellular roles, such as protein folding and refolding, regulation of cell signaling, response to unraveling proteins, regulation of calcium homeostasis, etc. Due to these roles, HspA5 has been widely studied as a therapeutic target in different types of diseases, including COVID-19. It is known that under stressful conditions, HspA5 can move to the plasma membrane and act as a cell receptor, interacting with viral proteins, such as the Spike protein of the new Coronavirus. Different studies have also shown that HspA5 is present in mitochondria, however, its network of interactions in mitochondria is poorly established. Experimental data from Protein Biochemistry and Biophysics group (IQSC/USP) demonstrated, in an unprecedented way, the interaction between NBD_HspA5 and human Hsp70-escort protein 1 (hHep1). Although hHep1 has been reported as an exclusive co-chaperone of the human mitochondrial Hsp70 (HspA9, mortalin), data from the research group demonstrate that hHep1 is also present in the nucleoplasm, and that it modulates the ATPase activity of HspA1A (main inducible human Hsp70). Therefore, hHep1 can modulate other Hsp70 present in the nucleoplasm and mitochondria. In this context, this project proposes: i) to map the in vitro interaction of HspA5 with the SARS-Cov2 Spike protein Receptor Binding Domain (RBD) and ii) to characterize the interaction mechanism of human proteins HspA5 and hHep1, as well as obtain the interactome of these proteins. For this, the recombinant human HspA5 proteins and the viral RBD_Spike will be expressed and purified, inorder to study the formation of the protein complex through biophysical techniques. In this context, the recombinant HspA1A and HspA8 proteins will be also used for comparative purposes. In addition, express and purify the heterologous NBD and PBD domains of human HspA5 and hHep1, in order to carry out the comparative mechanistic characterization of the interaction of hHep1 with HspA5 and its domains. The effects of hHep1 on the ATPase activity of HspA5 will also be evaluated, in addition to comparative assays of the action of hHep1 on the prevention of proteolysis and aggregation/oligomerization of the DLN of the HspA1A and HspA5 proteins. Additionally, cell assays will be carried out in order to evaluate the colocalization between HspA5 and hHep1, and to map the potential interaction between them and their cellular partners, through the BioID method combined with MS. Subsequently, it also aims to characterize the interaction between NBD_HspA5 and hHep1 through protein crystallography. Data from the research group indicate that evaluation of the interaction of hHep1 with HspA1A or HspA9 has technical limitations (unstable interactions or limited amounts of Hsp70). Therefore, the stable interaction with HspA5 can allow a comparative analysis of different human Hsp70 and allow considerable advances in the understanding of the molecular mechanisms of hHep1 over human Hsp70. Thus, an in-depth study of HspA5 will be carried out in order to elucidate processes of differential protein interactions and, consequently, obtain an integrated analysis of the cell processes in which hHep1 is involved. Therefore, the knowledge resulting from this project could serve as a basis for the development of new approaches for the treatment of human diseases, including COVID-19.",2021,2023,Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP),,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C15881,21/06128-5,Study of antiviral activity against SARS-CoV-2 OF copper nanoparticles and copper oxide supported in kefiran,"Copper nanoparticles (NPs) (CuNPs) and copper oxide (CuONPs) have antiviral and antimicrobial properties against various types of microorganisms and low production cost. Because of this, these NPs have been used in tests against SARS-CoV-2, the virus that causes COVID-19. It is currently known that transmission of bacteria and viruses, such as SARS-CoV-2, can occur due to the transport and use of contaminated food packaging. To this end, the development of packaging using polymers with antibacterial properties has grown a lot in recent years. In particular, the use of natural polymers has attracted attention due to the reduction of environmental impacts related to their disposal. With these motivations, the present work aims to synthesize CuNPs and CuONPs and to test the antimicrobial and virucidal activity of these NPs, pure and inserted in natural kefiran films, against Staphylococcus aureus and Escherichia coli bacteria and also against the SARS-CoV-2 virus. It is also intended to carry out mechanical and cytotoxicity tests of the films.",2021,2023,Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C15882,21/04590-3,"Exploratory analysis of functional lipidomics in the COVID-19 pathophysiology: molecular targets, metabolism and biochemical reprogramming due to hypoxia","Lipids represent the majority of biomolecules comprised in metabolomics. In this sense, a functional lipidomic configures an integrative strategy for the identification of bioactive lipids, membrane lipids composition, interactions of lipids with signaling proteins and metabolism enzymes. Consequently, lipids can influence pathological processes, such as inflammation and signaling of the tissue microenvironment. COVID-19 disease, caused by the SARS-CoV-2 coronavirus, can cause mild to critical illness. The critical cases present an exacerbated inflammatory response, and the lung may be the organ most affected. Metabolic diseases are mandatory as risk factors for COVID-19, but the mechanisms related to metabolism, especially those involving lipids, remain unclear. On the other hand, SARS-CoV-2 possesses a virus capsid surrounded by a lipid bilayer and the role of lipids in a viral infection comprises the fusion of the virus membrane to the host cell until the viral replication process. In this project, we propose a multidisciplinary approach to study the functional lipidomics applied in the pathophysiological processes of COVID-19, and we will use hypoxia as a model to evaluate biochemical reprogramming in this disease. Thus, we intend to: i) describe the plasma lipid composition of patients with COVID-19 in the broad severity illness; ii) characterize cell activation/signaling and metabolism pathways in blood leukocytes; iii) obtaining the monocytes subpopulations, determining their lipid composition and gene expression by Single-cell Lipidomics; iv) using the monocyte's lipidomics data for chemical imaging (MALDI) approach in bronchoalveolar lavage matrix or lung biopsy slides; v) determine the correlation of lipid metabolism and its bioactive metabolites in the modulation of SARS-CoV-2-induced inflammation and infectivity in monocytes in vitro, and vi) consider hypoxia as a modulator of lipid metabolism (in vivo and in vitro) and determine its effects on the disease pathology. Therefore, this study will clarify the involvement of lipid species in COVID-19 development and may suggest new molecular therapeutic targets",2021,2023,"Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP)",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2021 +C15883,21/03371-6,Impact of inflammasomes activation in central nervous system in response to ZikV e SARS-Cov2 infections,"Several viruses have the ability to invade the Central Nervous System (CNS), infecting resident cells and causing severe neuroinflammation by activating the innate immune system. Exacerbated inflammatory responses are influenced by the activation of inflammasomes, which are multiprotein platforms present in the cytosol of different cell types capable of activating the caspase-1 protease, leading to the secretion of IL-1² / IL-18 and cell death by pyroptosis. It has been shown that the Zika virus (ZIKV) modulates the activation of inflammasomes in different cell types. However, ZIKV mainly infects the CNS cells, and the role of inflammasome activation in these cells is not well established. Respiratory viruses can also damage the CNS similar as other well-known human neuroinvasive viruses. In this sense, SARS-Cov2 infection is increasingly being linked to neurological damage. It is known that infection with the new coronavirus stimulates a storm of inflammatory cytokines promoting Acute Respiratory Difficulty Syndrome (ARDS), fibrosis, hematological and neurological disorders, among others, which can result in organ failure and death. Recently, it was described the correlation between the activation of inflammasomes and the severity of COVID-19. However, the role of these platforms in the SNC is still unknown. Thus, considering the crucial role of inflammasomes for the host's response to pathogens and the potential of these platforms to exacerbating neuropathologies, the objective of this project is to elucidate the mechanisms by which inflammasomes are modulated in response to viral infections in murine and human CNS cells and its consequences for the control of infection and neuroinflammation.",2021,2023,Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo,,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Disease pathogenesis | Supportive care, processes of care and management",2021 +C15884,20/12630-2,Role of neutrophil extracellular traps (NETs) and platelet activation in immunothrombosis related to COVID-19 and inhibitory effect of substances that increase intracellular levels of cyclic nucleotides,"Approximately 14% of patients with coronavirus disease 2019 (COVID-19) have severe disease and 6% develop critical symptoms. The lethality of COVID-19 is around 4%. Severe symptoms manifest after approximately 7 to 8 days from the beginning of the disease, and progression to the critical form occurs on average after the 11th day of symptoms. The pathogenesis of COVID-19 is related to the invasion of the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) in the lung epithelial cells combined with the host's immune reaction. The uncontrolled systemic inflammatory response is the main mechanism behind severe acute respiratory syndrome and hypercoagulability. The latter is attributed to immunothrombosis, whose main participating cells are monocytes, which express tissue factor, neutrophils, which release extracellular nets composed of DNA, enzymes and histones (NETs) and platelets, through degranulation and aggregation. The aim of this project is to describe the association between the kinetics of NETS formation and platelet activation during hospitalization by COVID-19 and the occurrence of thromboembolic events, need for mechanical ventilation and death. We will also evaluate the capacity of patients sera to trigger NETS release and platelet activation and identify drugs capable of inhibiting the immunothrombosis process ""in vitro"". For this, we will a prospectively follow 100 patients with COVID-19 and will dose markers of NETs (MPO-DNA and H3 citrus), platelet activity (PF4 and RANTES) and inflammatory cytokines (TNF-±, IL-17a, IL-6, and IL-8) at 4 time points during hospitalization (admission, day +4, day +8 and last day of hospitalization). We will evaluate the association of the change in the pattern of these markers with clinical outcomes. We will perform culture assays on normal neutrophils with serum from patients and will measure the concentration of free DNA in the medium. We will perform platelet stimulation assays using patient sera and will measure the capacity of the stimulated platelets to aggregate and degranulate. Next, we will evaluate the inhibitory potential on NETs release and platelet activation of drugs that increase intracellular cAMP and cGMP concentrations, aspirin and enoxaparin. The results will allow: 1. to know the kinetics of the immunothrombosis process throughout the period of hospitalization by COVID-19, to identify the moment in the evolution of the disease in which there is the greatest alteration of this phenomenon and to associate it to the occurrence of adverse clinical outcomes; 2. to identify drugs with the potential to inhibit the release of NETs and platelet activation ""in vitro"", whose therapeutic efficacy may be tested in the future for the treatment of COVID-19 and other diseases associated to immunothrombosis.",2021,2023,Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2021 +C15885,21/10373-5,Using pre-clinical models to determine molecular candidates that contribute to the higher risk of COVID-19 during aging,"COVID-19 has emerged as an age-related disease whose mechanisms are still poorly understood. Using a combination of hypothesis-oriented and unsupervised, data-driven approaches, as well as patients and pre-clinical models, we expect to come up with candidate proteins and pathways which could not only predict the susceptibility to the disease, but also unveil the molecular mechanisms through which aging contributes to SARS-Cov-2 infection. We also expect to provide candidate FDA and ANVISA approved drugs which could potentially target these pathways to prevent, mitigate or eliminate virus infection. Our overarching aim is to elucidate how aging constitutes the main risk factor for COVID-19, providing potential solutions to its pandemic.",2021,2022,Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP),,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease susceptibility",2021 +C15886,20/06471-9,Immunogenetic markers of clincial evolution of COVID-19,mild and severe] and asymptomatic) favours the immunogenic understanding of humans in the face of SARS-CoV-2 infection and clinical evolution of COVID-19.,2021,2023,Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C15887,20/11803-0,Biosensors for dual detection of SARS-CoV-2 combining SERS and electrochemical impedance,"The global emergency situation due to SARS-CoV-2 demands the development of fast, reliable and low-cost methods for diagnosing the virus. The diagnostic gold-standard is the RT-PCR (Reverse-Transcription Polymerase Chain Reaction), which requires time, specialized operator and expensive equipment. In contrast, methods based on serological immunoassays may be relatively faster and less expensive, but are subject to high variability in the patients' immune response. In this project, we propose a detection assay encompassing an immunomagnetic separation and preconcentration followed by dual detection via SERS (Surface-Enhanced Raman Scattering) and electrochemical impedance in a sandwich configuration. For immunomagnetic separation, magnetic core and gold shell nanoparticles (Au@MNP) will be produced, properly functionalized with a SERS marker (4-mercaptobenzoic acid, 4-MBA) and monoclonal anti-SARS-CoV-2 Spike (S) protein (capture antibody, Ab1) forming Au@MNPAb1 conjugates. These conjugates will be incubated with samples containing the S glycoprotein SARS-CoV-2 (antigen, Ag), thus forming Au@MNPAb1Ag conjugates which after magnetic extraction, will be sequentially incubated on a gold sensing surface functionalized with polyclonal anti-S glycoprotein SARS-CoV-2 antibodies (detection antibody, Ab2) for dual electrochemical (by electrochemical impedance spectroscopy) and SERS detection. The sandwich approach using the Au@MNPAb1 conjugates must guarantee specificity, facilitate separation, purification and preconcentration, as well as act as a signal amplifying agent, both for electrochemical impedance measurements and for SERS. In the context of the thematic project 2018/22214-6, we expected to obtain collaborations with specialized groups so that, after sensor manufacturing and optimization through the S proteins, tests can be carried out on real samples infected with SARS-CoV-2.",2022,2022,Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +C15888,21/09539-6,Neutrophil Extracelular Traps (NETs): role in the pathophysiology and potential as a therapeutic target on COVID--19,"The disease caused by Coronavirus in 2019 (COVID-19) is caused by Coronavirus-2 of Severe Acute Respiratory Syndrome (SARS-CoV-2) and has become an important health problem worldwide. The pulmonary changes observed in patients with COVID-19 are characterized by intense damage to epithelial and endothelial cells, viral replication in pulmonary tissue and extensive inflammatory process characterized by edema, infiltration of inflammatory cells, including neutrophils and increased tissue concentrations of inflammatory cytokines , such as TNF-±, IL-1 and IL-6. In addition to pulmonary changes, there is also a systemic inflammatory response with important lesions in other organs such as kidneys, heart and intestines. Recent studies suggest that neutrophils participate in lung injuries and possibly in other organs, but it is not yet clear what mechanisms are involved. Among the cytotoxic mediators released by this cell type are free radicals, enzymes and NETs (from Neutrophil Extracellular Traps) or, simply, extracellular traps of neutrophils, which are networks of DNA conjugated with antimicrobial enzymes such as myeloperoxidase (MPO), elastase and citrullinated histones. NETs are described as one of the main mediators responsible for injuries seen in several autoimmune diseases and also in vital organs during sepsis. However, the involvement of NETs in the injuries observed at COVID-19 remains unknown. Therefore, the objective of the present project is to identify the participation of NETs in the pathogenesis of COVID-19. The possible involvement of NETs in the pathogenesis of COVID-19 will allow us to propose new therapeutic approaches for this disease, that is, drugs that degrade this mediator and/or inhibit its synthesis. In this sense, we are also proposing to conduct an open clinical trial treating patients with COVID-19 with Pulmozyme. Pulmozyme is used in the clinic to treat cystic fibrosis and its active ingredient is DNAs that degrade NETs. Confirming the feasibility of the project, in a preliminary experiment, we observed an exacerbated production of NETs by isolated neutrophils and in the plasma of patients affected with COVID-19.",2021,2022,Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP),,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Prophylactic use of treatments | Clinical trial (unspecified trial phase),2021 +C15889,21/03421-3,Inflammatory and functional imaging aspects of COVID-19: analysis of PET/CT and pulmonary perfusion scintigraphy imaging findings,"COVID-19 disease caused by the new coronoavirus (SARS-CoV-2) has killed almost 2.5 million people worldwide, 250 thousand of which registered in Brazil, and the discovery of new mutations is indicative that pandemic condition is expected to last in the coming months. Clinical picture and outcome of COVID-19 patients are very heterogeneous and studies on functional imaging, inflammatory and coagulation profile are justified. There is evidence that COVID-19 patients may develop disseminated intravascular coagulation, with prothrombotic nature and high risk of venous thromboembolism, especially pulmonay (PTE), which has a substantial impact on evolution and increases mortality. D-dimer, fibrinogen and thrombin time assessments may contribute to minimize the consequences of PTE. In addition, a prospective study of functional imaging such as pulmonary perfusion scintigraphy and 18F-FDG PET/CT will be able to evaluate the validity of these methods for detecting PTE in small vessels and early changes in lungs and other organs affected by the disease. Therefore, the major objective of this work is to assess the sensitivity of pulmonary perfusion scintigraphy in detecting early lung involvement, in particular PTE, and the sensitivity of 18F-FDG PET/CT in detecting early inflammatory changes in the lungs (and others organs) of these patients. We believe that this study may have a relevant impact on the management of COVID-19 patients.",2021,2023,Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP),,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,Americas,,,,Brazil,Brazil,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2021 +C15892,SRG2021\210686,Work and crisis management on supermarket frontline in the COVID-19 pandemic,,2021,-99,University of Greenwich,12462.94,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C15893,SRG2021\210376,The impact of the Covid-19 pandemic on trade flows and patterns: evidence from Europe,,2021,-99,Brunel University London,13764.51,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C15894,SRG2021\211073,"Feeling, making and imagining time: Everyday temporal experiences in the Covid-19 pandemic",,2021,-99,University of London,13779.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C15895,SRG2021\211384,Socially responsible banking: Weathering the COVID-19 storm,,2021,-99,University of Essex,13734.38,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C15896,SRG2021\211338,Risk and resilience in radically redefined information environments; Information practices during the COVID-19 pandemic,,2021,-99,University College London,9882.4,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C15897,SRG2021\210830,Solidarity and Care During the Covid-19 Pandemic: A Transnational Collaboration in Public Sociology,,2021,-99,London School of Economics and Political Science,12707.47,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C15898,SRG2021\210772,Fighting the disinformation pandemic (Infodemic): Platform Governance in the UK and Taiwan amid COVID-19,,2021,-99,N/A,6799.03,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,,Europe | Western Pacific,,,,,United Kingdom | Taiwan,"Policies for public health, disease control & community resilience",Communication, +C15899,SRG2021\211285,A signal-detection theory analysis of public beliefs around COVID-19,,2021,-99,University of Essex,13728.86,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C15900,SRG2021\211013,An Experimental Evaluation of the Role of Overconfidence on Personal Attitude toward COVID-19 and Risk Mitigating Factors,,2021,-99,University of Sussex Business School,13701.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions, +C15901,SRG2021\211031,"Institutional rainbowification before, during (and after?) COVID-19: a case study of HE",,2021,-99,Sheffield Hallam University,13760.57,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C15902,SRG2021\211425,Signs of the Times: Examining the intended and unintended consequences of shop closure communications during the pandemic in 2020 - a semiotic anthropological and customer perspective,,2021,-99,University of Nottingham,10683.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C15903,SRG21\211358,"Assessing the impact of COVID on the social networks, supports, and wellbeing of people convicted of sexual offences and their families",,2021,-99,University of Derby,13765.11,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts, +C15904,SRG21\210308,Recovery Position? Narratives of community-led recovery from the COVID 19 pandemic: The case of the East Midlands,,2021,-99,King's College London,10009.77,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement, +C15905,SRG21\211503,Uncertainty Paradox: Why You Should (Not) Lie about COVID-19 statistics,,2021,-99,University of Bristol,13772,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Communication, +C15906,SRG21\211061,Cognitive Trajectory of COVID-19: Pre- versus Post-COVID-19 Cognitive Function in Survivors,,2021,-99,Brunel University London,13627.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences, +C15907,SRG21\211097,Locked down and locked out? The impacts of the COVID-19 pandemic on mothers working in UK television,,2021,-99,University of Nottingham,13608.29,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C15908,SRG21\211615,All hands on deck? Organisational hybridity and the voluntary response to critical shortages of PPE during the COVID-19 pandemic in England,,2021,-99,N/A,13416.68,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified | Not applicable,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,,Europe,,,,,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C15909,SRG21\210010,Prevalence of food fraud and resilience strategies of the UK food supply chain during COVID-19,,2021,-99,University of Central Lancashire,9626.63,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C15910,SRG21\210622,Disturbing images: visualising the COVID-19 pandemic at India's margins,,2021,-99,University of Leicester,13565.42,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,South-East Asia,South-East Asia,,,,India,India,,, +C15911,SRG21\211038,"The political discourses and practice of media freedom in the UK since 2016: Brexit, COVID-19 and National Politics",,2021,-99,University of Sheffield,10512.17,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C15912,SRG21\211083,Minority ethnic older adults' perception of COVID-19 public health campaigns,,2021,-99,University of Greenwich,13584.08,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement, +C15913,SRG21\210667,Living through the pandemic in post-Brexit Britain: emotional damage and forms of resilience among middle-aged European citizens,,2021,-99,Robert Gordon University,12232.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts, +C15914,SRG21\210800,Building resilient local economies and communities post - pandemic through entrepreneurial action in the Circular Economy,,2021,-99,University of Sussex,13303.75,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,British Academy,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts, +C15941,TMA2020CDF-3101,i-PUSH-RCT - Examining the impact of maternal perinatal depression on child health outcomes and the role of Innovative Partnership for Universal and Sustainable Healthcare (i-PUSH) intervention: a cluster randomised controlled trial study,"Background: The burden of maternal perinatal depression in low- and middle-income countries (LMICs) and its consequences on child health and development are emerging public health problems and are of high priority. Although the pathways connecting maternal perinatal depression and poor childhood outcomes are likely to be complex and varied, perinatal depression during this critical period is more likely to lead to offspring with poor health, development and nutrition outcomes. However, data on maternal mental healthcare, including perinatal depression, is meagre, with limited evidence on feasible detection and treatment strategies, lack of specialist services, lack of guidelines for pregnant and breastfeeding mothers, and stigmatising attitudes among primary healthcare workers and the community. This study aims to investigate the effect of maternal perinatal depression on child health, developmental and nutritional outcomes and whether an innovative partnership for sustainable and healthcare (i-PUSH) intervention using digital technology (mhealth) modifies perinatal depression and its effect on child health, development and nutrition. Methods: This is a longitudinal cluster randomised controlled trial study that uses weekly Health diaries data in Khwisero Sub-county, Kenya. The study aims to evaluate the i-PUSH program-a comprehensive intervention that primarily aims to improve the utilisation of Reproductive and Maternal and Child Health services among women of reproductive age and their young children. The plan is to collect additional data on early childhood development and maternal mental health in relation to COVID-19 pandemic and conduct rigorous analyses of the existing and newly added data from the ongoing i-PUSH study and incorporate capacity building and career development components. The study protocol for the main study was reviewed and approved by the AMREF Health Africa Ethical and Scientific Review Board. New approval will be sought for the new data collection and extension of the analyses. Discussion: The proposed study supports Sustainable Development Goal (SDG) 3 - 'ensure healthy lives and promote wellbeing for all at all ages'. It is particularly important to achieve SGD goals related to maternal and child health (SGDs 3.1 and 3.2) and reducing premature mortality from non-communicable diseases through prevention and treatment and promote mental health and wellbeing (SDG 3.4). The applicant is trained abroad, and an early career researcher (a postdoctoral research scientist) based in Africa at an African-focused research institute. This Career Development Fellowships is a unique opportunity for the applicant's career and professional development both at regional and international levels. It also builds the applicant's research capacity towards independent researcher in maternal and child health research and retains the fellow in sub-Saharan Africa for his future endeavours and contributions.",2021,2024,African Population and Health Research Center (APHRC),176700,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Women | Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Africa,Africa,,,,Kenya,Kenya,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C15942,TMA2020CDF-3212,CoVAT - Development and Deployment of Lateral Flow Antigen Test for COVID-19,"Abstract: COVID-19 is a newly emerged infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that continues to pose serious threat to global health, devastating world economy and lifestyles. Testing has been recognised as a key step in mitigation of spread of the disease since it allows for prompt clinical and well-tuned public health interventions including physical distancing measures. The current predominant testing strategy is based on the detection of SARS-CoV-2 from nasopharyngeal and/or oropharyngeal specimen by reverse transcription polymerase chain reaction (RT-PCR). Although RT-PCR is highly sensitive, it is expensive, requires skilled manpower, equipment and has a long turnaround time of up-to 24 hours. This has greatly restricted its large-scale deployment especially in low- and middle-income countries (LMICs) including Kenya. Similarly, lately developed serological tests for COVID-19 have been observed to have low sensitivity and specificity, reducing their utility. Moreover, they provide information on historical infection which may not be clinically useful. Thus, antigen-based tests for SARS-CoV-2 offer an attractive alternative solution to testing needs and possibly the only viable solution for most LMICs. Lateral Flow Antigen (LFA) tests in particular are suitably inexpensive, can be rapidly mass-produced, are easy to use, return results in minutes, and crucially, like RT-PCR and unlike serological tests, can reveal an active infection. As of July 19th, 2020, only two antigen tests had received emergency use authorization. These authorized assays require instrumentation and are not available at low cost or outside health care settings. Hence, to address these diagnostic challenges, we propose to develop an LFA test for COVID-19 that will be affordable, easy to use and does not need skilled personnel, expensive reagents nor machines. Since sufficiently accurate performance of an LFA test requires highly optimized antibodies and assay conditions, we shall leverage on an innovative high-throughput eukaryotic wheat germ cell free system to generate 5 COVID-19 antigens derived from locally circulating SARS-CoV-2 sequences. We shall then use these antigens to produce monoclonal antibodies in mice and the most efficient capture and detector pairs of antigen specific antibodies will be mounted on lateral flow strips for rapid point-of-care diagnostic test. We shall then evaluate the implementation outcomes- feasibility, acceptance, and cost effectiveness and user friendliness- of the LFA point-of-care test to inform adaptation and future scale up.",2021,2024,Mount Kenya University Trust (MKU),177705,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Africa,Africa,,,,Kenya,Kenya,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C15943,RIA2020S-3295,XACT-19 - Evaluating the impact of computer-assisted x-ray diagnosis and other triage tools to optimise Xpert orientated community-based active case finding for TB and COVID-19,"Abstract: A startling statistic is that over 40% of TB cases in endemic countries are ""missing"" (~3 million cases globally remain undiagnosed or unreported)! Most of these undiagnosed cases, which continue to transmit disease, are concentrated in the peri-urban 'slums' and 'shanty towns' of large African cities. Without addressing the 'missing cases' the TB epidemic will never be controlled. Unfortunately, the same communities have now been ravaged by the COVID-19 pandemic and outbreaks are likely to occur for some time to come. A strategy is therefore required to seamlessly detect TB and, when warranted, COVID-19 in the same communities. Over the last 5 years we have optimised a model for Xpert-orientated community-based active case finding for TB (XACT; Appendix, additional information, Figure 3). In XACT 1 we showed that community-based screening with molecular diagnostic tools (Gene Xpert) is highly effective in detecting the missing cases (Calligaro & Dheda, Lancet Infect Dis, 2017). In XACT II (recruitment complete and submitted for publication) we confirmed the feasibility and validated the use of scalable XACT model using battery-operated, point-of care (POC) Xpert-Edge for community-based ACF using a low-cost panel van (XACT II; NIH-funded; n= 5500 participants). XACT III is currently recruiting and is a demonstration project of this scalable model in multiple African countries and will also clarify how Xpert should be best located (POC compared Xpert performed in a centralized laboratory; Wellcome Trust and UKMRC-funded & EDCTP co-funded). Funding of ~€5.5 million is now being requested for a study that seeks to determine the utility of computer-assisted x-ray diagnosis (TB-CAD), as a triage tool, to further optimise the XACT model (XACT-19). Thus, we will screen community-based participants and perform an RCT to determine the impact of a CAD + Xpert versus Xpert-only strategy for ACF in symptomatic or HIV-infected participants. In addition, we will determine the utility of TB-CAD and Xpert in asymptomatic HIV-uninfected persons. In the same cohorts we will investigate the utility of COVID-CAD and Xpert COVID cartridges for community-based detection of COVID-19. We will also opportunistically evaluate the utility of nascent community-based urine-orientated triage tests for TB and COVID-19 (these will involve an African-based SME). Co-funding of ~€ 1.6 million has been leveraged. In summary, this proposal (XACT-19) will likely define a new standard of care for TB (and COVID-19 ACF) and revolutionize TB detection, moving it out of clinics and into the community.",2021,2025,The University of Cape Town Lung Institute (Pty) Ltd,6640296.23,Human Populations,Unspecified,Unspecified,Suburban Population/Setting,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Africa,Unspecified,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C17230,86134,COVID-19 Secure and Clean Indoor Air Environment for Schools (COVID-SIS),"As children across the UK are preparing to return to schools (i.e. where they spend the majority of their time after their home), it is more important than ever to ensure that children's exposure to harmful pollutants is minimised. For instance, outdoor air pollutants from vehicle emissions (e.g. PM2.5, NOx) can enter classrooms through open doors and windows during peak times. Similarly, harmful air pollutants (e.g. Aerosols, CO2) which are known to be detrimental to children's health are also being generated inside classrooms. In particular, a growing body of epidemiological evidence (e.g. Wang & Du, 2020; Huffman et al., 2020) suggests that aerosols (i.e. chemicals emitted by building materials, furnishings, electronics) can become active transporters of COVID19\. To ensure that schools have a Clear-Air learning environment and are COVID-secure, it is vital to monitor the presence of these harmful indoor air pollutants (e.g. Aerosols, PM, SO2, CO2, NOx). Even though schools have introduced several pandemic precautions (e.g. physical distancing, staggered mealtimes, regular cleaning), no school currently has a digital tool/platform that allows **school administrators** to monitor and take proactive actions on the presence of indoor air pollutants. It is on this premise that this solution will for the first-time combine state-of-the-art technologies such as IoT and AI to develop a **COVID-19 Secure and Clean Indoor Air Learning Environment for Schools (COVID-SIS)**. COVID-SIS will have three modules; they include: 1. **IoT-Multi Pollutant Sensing Module (IoT-PSM):** will leverage low-cost, off-the-shelf and state-of-the-art IoT sensors to monitor the real-time trace amounts of indoor air pollutants in schools. IoT-PSM will collect and transmit indoor air pollutants data from areas of interests to the cloud server for insightful analyses. 2. **AI-Multi Pollutant Analytics Module (AI-PAM):** will directly communicate with the data being streamed from IoT-PSM to facilitate advanced AI analytics of indoor air pollutants data. They include: * **(a) Descriptive-AI:** will provide in-depth information on the concentration of pollutants in areas of interests. * **(b) Diagnostic-AI:** will provide factors responsible for specific pollutant trends. * **(c) Predictive-AI:** will understand hidden trends in historical and current pollutant data and providing step-change day-ahead forecasting of pollutant concentration. * **(d) Prescriptive-AI:** will provide the proven best course of action to improve the health and safety of indoor air to school administrators. 3\. **Web Based-Multi Pollutant Visualisation Platform (Web-PVP):** will allow school administrators with little-or-no expert knowledge to quickly visualise the trace amounts and advanced AI analyses of indoor air pollutants in areas of interest.",2020,2021,GLENTROX (UK) LTD,235368.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C17231,86134,COVID-19 Secure and Clean Indoor Air Environment for Schools (COVID-SIS),"As children across the UK are preparing to return to schools (i.e. where they spend the majority of their time after their home), it is more important than ever to ensure that children's exposure to harmful pollutants is minimised. For instance, outdoor air pollutants from vehicle emissions (e.g. PM2.5, NOx) can enter classrooms through open doors and windows during peak times. Similarly, harmful air pollutants (e.g. Aerosols, CO2) which are known to be detrimental to children's health are also being generated inside classrooms. In particular, a growing body of epidemiological evidence (e.g. Wang & Du, 2020; Huffman et al., 2020) suggests that aerosols (i.e. chemicals emitted by building materials, furnishings, electronics) can become active transporters of COVID19\. To ensure that schools have a Clear-Air learning environment and are COVID-secure, it is vital to monitor the presence of these harmful indoor air pollutants (e.g. Aerosols, PM, SO2, CO2, NOx). Even though schools have introduced several pandemic precautions (e.g. physical distancing, staggered mealtimes, regular cleaning), no school currently has a digital tool/platform that allows **school administrators** to monitor and take proactive actions on the presence of indoor air pollutants. It is on this premise that this solution will for the first-time combine state-of-the-art technologies such as IoT and AI to develop a **COVID-19 Secure and Clean Indoor Air Learning Environment for Schools (COVID-SIS)**. COVID-SIS will have three modules; they include: 1. **IoT-Multi Pollutant Sensing Module (IoT-PSM):** will leverage low-cost, off-the-shelf and state-of-the-art IoT sensors to monitor the real-time trace amounts of indoor air pollutants in schools. IoT-PSM will collect and transmit indoor air pollutants data from areas of interests to the cloud server for insightful analyses. 2. **AI-Multi Pollutant Analytics Module (AI-PAM):** will directly communicate with the data being streamed from IoT-PSM to facilitate advanced AI analytics of indoor air pollutants data. They include: * **(a) Descriptive-AI:** will provide in-depth information on the concentration of pollutants in areas of interests. * **(b) Diagnostic-AI:** will provide factors responsible for specific pollutant trends. * **(c) Predictive-AI:** will understand hidden trends in historical and current pollutant data and providing step-change day-ahead forecasting of pollutant concentration. * **(d) Prescriptive-AI:** will provide the proven best course of action to improve the health and safety of indoor air to school administrators. 3\. **Web Based-Multi Pollutant Visualisation Platform (Web-PVP):** will allow school administrators with little-or-no expert knowledge to quickly visualise the trace amounts and advanced AI analyses of indoor air pollutants in areas of interest.",2020,2021,NOVELTRIC (UK) LIMITED,234560.3,Other,Not applicable,Not Applicable,Not applicable,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +C17754,AH/R002029/1,Lifting the Lid on Bacteria': Designing ambient communications to improve hygiene in primary school toilets,"Context: AMR can be directly tackled by reducing the spread of infection in the first instance. The primary school toilet is a risk-laden space for the spread of bacterial infection given the behaviour of its users. Research reports that fewer than half of the children who use school toilets wash their hands afterwards. Neutral poster-based messages such as 'Now Wash Your Hands' or classroom material may aid understanding and reinforce hand hygiene messages but what is the potential of using more novel, engaging, friendly and site-specific communication in the toilet environment itself? Aims and objectives: The primary aim of this communication design-led research is to investigate the potential of using ambient, surface-based communications in the primary school toilet environment to improve hand hygiene practices (lowering the toilet lid, hand washing and hand drying). Ambient communication involves the clever and unexpected integration of graphics and media messages in specific environments. It is usually employed by commercial companies to improve engagement with a product or brand but it holds much potential for application in other areas. If bacteria and other appropriate message/images were clever represented in the environment, for instance, what impact would it have on behaviour in that space? This research involves three phases. Firstly a historical review of everyday representations of bacteria and hand hygiene aimed at children will be carried out. This will provide new knowledge of dominant ideas from the 20th Century about children, hygiene and bacteria and provide selected imaginative material to show to children in subsequent workshops. Secondly school children will be directly engaged with to gauge their understanding of the toilet space, what bacteria might look like there and where it is. Participatory design methods will be used to understand what children would design and why. Thirdly a set of ambient designs will be developed, informed by historical and contemporary design practice and children's imaginative ideas, for testing in school toilets and the toilets at Eureka! The National Children's Museum. The installation of the designs will facilitate the testing of the concept and provide opportunity for a pilot study of evaluation methods - what are the most effective and feasible ways to measure success of such an intervention? Applications and Benefits. This interdisciplinary, collaborative research project brings together academics and professionals from the areas of communication design, medical history, healthcare, education and microbiology. The project will involve a synthesis of approaches (historical analysis, participatory design methods, communication design practice, and science-led evaluation methods) and thus the application of the research is potentially wide. It can inform medical and public health historians about historical and contemporary ideologies underpinning bacteria representations aimed at children. It can also provide communication designers with an extensive set of designs and analysis to aid the designing of anti-bacterial products/interventions for children today. It will also bring microbiology research into a more public domain since we will use findings directly from microbiology research (related to toilet lid position) for one of the messages. The designs developed may also be applied not only within school toilets more widely but in children's hospitals or wards. One of the key benefits of the research, if the intervention is successful, is potentially reducing the spread of infection due to school toilet usage. There are number of benefits to this aspect of the work alone: reducing absenteeism, reducing the occurrence of infections within the wider family, and reducing the request for antibiotics. The research will promote discussion amongst teachers and child-focused museums about current and potential future communications in the toilet space.",2021,2019,University of Leeds,264899.64,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2017 +C17755,AH/V006991/2,Using multisensory culture boxes to promote public health guidance and to support the wellbeing of people with dementia in care homes.,"This study addresses two urgent challenges. Firstly, providing COVID-19 (CV-19) information for those with cognitive impairment, specifically people with dementia in care homes. Secondly, alleviating social isolation and loneliness in care homes by providing creative activities that support wellbeing for people with dementia, especially, in the context of long-term CV-19 lockdown and restrictions. This project will produce, distribute and evaluate CV-19 culture boxes incorporating pandemic guidance with creative activities to support health and wellbeing and alleviate social isolation and loneliness for people with dementia in care homes. The team will work with the Geller Institute of Ageing and Memory (IAM), stakeholders including people with dementia, staff and family carers and allied professionals, including BAME representatives, to co-design culture boxes with artists. These will be delivered weekly for 3 months (then repeated, updated, for 12 months). Each will contain multisensory materials (subject to health and safety guidance) suitable for diverse populations that: provide information about CV-19 transmission and prevention, with creative resources including music and art activities that are simple to implement and offer stimulation and enrichment. The weekly delivery aims to reinforce public health messaging and to mimic regular activities in care homes. The National Activity Providers Association (NAPA) will support distribution via their network of 3000 members. The project will be evaluated using Participatory Action Research (PAR). All resources will be archived via the NAPA website ensuring that they are widely available. Dissemination includes an art exhibition, conferences, educational presentations, and a peer-reviewed paper.",2021,2021,University of Exeter,270126.75,Human Populations,Other | Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other | Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2021 +C17756,AH/V013874/1,"HEartS Professional: The Health, Economic and Social impact of COVID-19 on PROFESSIONALs in the ARTs","The arts and culture sectors play a vital role in connecting and inspiring communities. In the COVID-19 crisis, these sectors are also among the most disrupted, with performances, exhibitions and exchanges of all kinds all but halted. The arts and cultural economies, and those who work within them, face unprecedented challenges and uncertainty. HEartS Professional addresses this by investigating the health, wellbeing and financial impact of the crisis on professionals in the arts and culture sectors, providing knowledge, leadership, advocacy and new ways forward when and where they are needed most. The project surveys arts and culture professionals to determine precisely where challenges lie and how they evolve as the crisis unfolds, responding to those challenges with targeted investigations. It celebrates innovative responses to the crisis and shares examples of good practice. Moreover, it explores how digital tools can be quickly designed, adapted and implemented to ensure that culture and arts professionals have available new methods to sustain their practices and serve their communities.",2021,2022,Royal College of Music,526303.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C17757,AH/V015540/1,Making it FAIR: understanding the lockdown 'digital divide' and the implications for the development of UK digital infrastructures,"This proposal responds to challenges faced by smaller museums struggling to engage online with audiences during varying levels of lockdown, and beyond. Problems include: low levels of basic digital literacy; poor understanding of audiences (including those with specific access needs); uncertainty over how to transfer real-world interpretive practice to the digital realm; lack of guidance about technical solutions; barriers to future-proofing digital assets in line with the FAIR data principles (data should be Findable, Accessible, Interoperable and Reusable); and shoestring budgets. The project will create a community of practice that will (through sector-wide dissemination) extend beyond the immediate participants to museums across the UK. The core cohort will receive training, mentoring and technical support to develop digital collections-focussed content to stay connected with existing audiences, and reach new audiences. Technical support will, as appropriate, pilot solutions (based on integration of existing tools) and demonstrate how a fully-developed infrastructure for cultural heritage data, when coupled with digital skills support, might benefit even the smallest museums, as well as well-resourced and digitally-savvy IROs. This community of practice will explore prototype solutions for user-group testing, that respond directly to emerging challenges, informing the TaNC discovery process. The study is action research with a cohort of staff and/or volunteers from small museums, who will create online content based on their collections. The methodology is built around the collaborative action research approach developed by Culture 24 over a number of previous projects but adapted for delivery online in a time of home-working and social distancing. The hallmarks of the approach are: Learning from others - including a variety of voices and perspectives from within and beyond the cultural sector, to inform, support, guide and reflect on the challenges at hand. Learning by doing - encouraging practical action research and supporting participants to experiment in the context of their everyday work, testing out hunches developed through collaborative discussions. Learning together - creating a community of supportive peers with a shared sense of purpose, turning them into invaluable sources of understanding for the wider cultural heritage sector. As well as the core collaborative action research, the study will include a socio-technical challenge: as the participants encounter difficulties along the way, the project team will respond where possible and prototype simple tools that demonstrate how a fully developed infrastructure might support even - perhaps especially - the smallest and least resourced museums. This project will engage with six to eight smaller museums who have been navigating these challenges, reporting back to the wider museum sector, and helping others during the what for some have been make-or-break months. Through critical evaluation of current practice in microcosm through online workshops, and a technical gap analysis, the project will draw scalable lessons to inform Towards a National Collection's (TaNC) discovery phase, and AHRC's infrastructure planning.",2021,2021,University of York,128911.22,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +C17758,AH/W000288/1,Immunity passport service design: a user-centred approach to inform UK's national exit strategy from the lockdown,"We will apply a user-centred design approach to conduct research that contributes to our understanding of immunity passport services as part of the UK's COVID-19 exit strategy. These immunity or health passports would allow individuals who have antibodies of the SARS-COV-2, and are no longer carriers of the virus, to return back to work, travel or socialise without restrictions. Their use has formed part of many countries' exit plans. Yet, there is dispute among scientists, policy makers and the public that such interventions are based on many uncertainties that could put public health at risk, infringe privacy and lead to inequalities in society. To better understand this phenomenon, we will engage with key stakeholders to address the following questions: - What are the possible unintended consequences and risks of immunity passports? - What are the key stakeholders' requirements, resources, technologies and processes needed in the design of services around immunity passports in order to mitigate any unintended consequences? Our approach will involve interviews, focus groups and participatory design workshops. Key deliverables will be specifications for service design including blueprints and user journey maps. This application fits the following UKRI proposal type: 'new research or innovation with a clear impact pathway that has the potential to deliver a significant contribution to the understanding of, and response to, the COVID-19 pandemic and its impacts', and contributes to the following UKRI questions: What information should inform decision-making about emerging from lock-down (policy responses)? What are the unintended consequences of releasing data (Data Science/Engineering)?",2021,2021,Loughborough University,183513.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2021 +C17759,AH/W000407/1,A national Day of Reflection on the COVID-19 pandemic: lessons from past memorialisation initiatives and attitudes in the present,"The proposed project will focus on the evolution of public memorialisation in response to the COVID-19 pandemic. Partnering with the Marie Curie charity and its campaign for a national Day of Reflection in 2021, it will draw academic expertise on civic memorialisation together with stakeholder organisations (charities, faith groups, and public bodies) to examine two core issues. First, how new practices may be beneficially informed by scholarship on British public memorialisation of traumas in the 20th century. Second, how varied stakeholder opinions on the format, organisation, and narratives of a national Day of Reflection on COVID-19 can be critically integrated into the development of the memorialisation activities. In this way the project will look to both past precedents and the complexities of the present, building up an analytical framework that impactfully contributes to social responses to the pandemic. In undertaking this work the project will consider how memorialisation navigates several key relationships: between 'top down' state-led memorialisation and local agency; between memorialisation as a force for unity and the need to reflect social diversity; between mourning loss and celebrating achievements during the crisis; between varied forms of memorial ritual; between national self-validation and self-critical reflection. Outputs from the project will include a series of workshops that draw together memory studies scholars and non-HEI participants, an open-access written report for Marie Curie and other stakeholders that informs preparations for the national Day of Reflection, and a major conference paper and follow-up publication.",2021,2022,University of Exeter,33729.83,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C17760,AH/W000423/1,"Combatting gendered, sexual risks and harms online during Covid-19: Developing resources for young people, parents and schools.","This study seeks to assess the impact of COVID-19 and social isolation on young people's experiences of online sexual risks and gendered harms during a period of increased reliance on screens. Through surveys and focus group interviews with up to 2k young people (ages 13-21) and 100 parents/carers, the study will address gaps in knowledge by exploring young people's differing experiences of online sexual harassment during Covid-19, in relation to gender (girls, boys, gender non-conforming), sexuality (LGBTQI+) and other intersecting identities. The study's central aim is to develop a set of interactive digital resources that provide accessible and tailored advice and information for young people, teachers, and parents, on how to stay safe online during the pandemic and beyond. These digital resources will be piloted and tested in 5 UK schools, before being launched online and delivered by our partners, the award-winning sex education organization School of Sexuality Education (SSE), and the Association of College and School Leaders (ASCL) with combined access to over 20k schools across the UK. All resources will be freely available through SSE's website and be promoted by our project partners. Finally, working closely with key stakeholders [such as the Child Exploitation and Online Protection (CEOP)], we will also produce a final report with advice and guidance for schools, parents, and tech companies on what is needed to better protect young people, including ways to report online sexual harassment and how to seek help.",2021,2021,University of Leicester,232957.97,Human Populations | Other,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Indirect health impacts | Social impacts | Cross-cutting,2021 +C17762,BB/E018521/1,Autophagy represents a new host-pathogen interface for identification of infectious bronchitis virus proteins that determine virulence,"Infectious bronchitis is an important endemic disease of chickens and caused by the avian coronavirus infectious bronchitis virus (IBV). Poultry meat is an important food source and during the course of a year approximately 40 x 109 chickens are reared globally. The increasing demand for poultry meat has lead to the introduction intensive farming methods but productivity is often limited by infectious diseases which spread rapidly through high density chicken populations. Importantly for this proposal, a report sponsored by the UK government published in 2005 (http://www.defra.gov.uk/science/Project_Data/Document Library/ZZ0102/ZZ0102 1215_FRP.doc) revealed that the number one cause of economic loss in the UK poultry industry resulting from infectious diseases of chickens was caused by IBV. The virus is not only responsible for respiratory disease, but also causes damage to the kidneys and to egg producing organs of hens, affecting both the production and quality of eggs. Despite the availability of live and inactivated vaccines, IBV continues to be a major problem. The virus causes high morbidity, is ubiquitous world wide, and endemic in the UK, and shows extensive antigenic variation and short lived immunity. These factors lead to high rates of infection and poor cross-protection following infection or vaccination. Most vaccines are given to poultry by spray or in drinking water. Both approaches are rather hit-and-miss. The 'holy grail' of vaccine developers is to have vaccines that can be given by robotic machine to chicks before they hatch. Unfortunately, no existing IB vaccine can be given in ovo because the viruses stop the chicks hatching. One means of controlling IBV is to have a systematic way of generating live attenuated vaccines that provide protection against virulent strains. The reverse genetics necessary for the modification or removal of genes associated with virulence from IBV has been developed by the coronavirus group at the IAH Compton. Together with DEFRA and Intervet International, a major commercial vaccine developer, the IAH coronavirus group are manipulating the genes of IBV to get an optimum balance between attenuation of virulence and capacity to induce immunity. To apply this technology to the rational design of live vaccines it is now necessary to identify genes that contribute to IBV virulence, and understand how they function. Importantly for this proposal, recent work on mammalian coronaviruses, and work on the avian IBV coronavirus at Compton, suggests that virulence may be determined by the way in which cells control virus replication. We have produced IBVs that do not make a series of small proteins called 3a, 3b, 5a and 5b. These viruses grow normally in cell culture and allow chicks to hatch after inoculation in ovo. This shows that we can attenuate IBV by removing non-essential genes, but this is an empirical process because we do not know how the 3(ab) and 5(ab) proteins function in the context of virulence. The purpose of the present grant application to BBSRC is to establish the science behind the empirical observations that we are making. Experiments underpinning this proposal have shown that virulence of IBV may be associated with proteins that control replication, and that these proteins associate with membranes in cells that have the potential to destroy the virus before it can leave the cell. We now want to understand how the replicase proteins avoid destruction, and in this way determine virulence. This will enable us to fine tune our mutants to make viruses that survive long enough to infect chicks 'in ovo', and induce an immune response, but are too weak to harm the chicks and prevent them from hatching.",2021,2011,University of East Anglia,357521.33,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2008 +C17764,BB/G012067/1,Coronavirus polymerases: functions and subunit interactions,"Viruses are major causes of disease in humans and animals. They evolve very rapidly through diverse genetic mechanisms, resulting in a constant threat to animal and human health by newly emerging viruses for which no vaccines and drugs are available. To combat virus infections more effectively, a detailed understanding is required of the molecular details of the viral life cycle and the biological molecules that viruses require to multiply in animal and human hosts. Molecular information obtained for specific families of viruses can subsequently be used to develop drugs that very specifically inhibit essential virus structures and functions without disrupting normal cellular functions, which obviously would cause toxic side effects during antiviral therapy. The proposed research investigates molecular details of the life cycle of coronaviruses, which are large RNA viruses causing respiratory and enteric disease in livestock, companion animals and humans. More specifically, the study focuses on the structures and functions of a multi-protein complex that is comprised of 16 viral and several cellular proteins and includes enzymes, called polymerases, that multiply the viral genome RNA, which is one of the essential steps in the production of new viruses. The focus of this research is to investigate the properties and functions of two coronavirus polymerases and their interactions with other proteins in the multi-protein complex. Using a range of molecular, biochemical and genetic methods, the work will produce valuable new insight into the molecular and mechanistic details involved in coronavirus replication. This will have broad applications to developing new strategies for antiviral therapy of infections caused by coronaviruses and similar viruses and help improve our understanding of cellular processes including those related to antiviral host responses.",2021,2012,Queen's University of Belfast,552384.12,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2009 +C17765,BB/H011285/1,Understanding the evolution and diversity of viral pathogens using next generation sequencing technologies,"A main cause of animal and human disease are infectious agents such as viruses. In this project we wish to study the genetic material of these pathogens. Genetic material is encoded as ordered 'sequences' of nucleotides. This information determine a virus' biological properties and response to the host immune system and thus the success of veterinary or medical treatments, whether they are vaccine or drug-based. Until very recently pathogen genetic material was characterized using Sanger sequencing, a technique invented in the late 1970s. More recently new sequencing technologies have become available that permit extremely large numbers of sequence fragments, called 'reads', to be generated. Many are referring to this as a revolution in sequencing because it now permits small groups of researchers to tackle projects previously only possible at sequencing centres, while sequencing centres can tackle truly massive sequencing projects, for example, the initiative to sequence 1,000 human genomes. This introduces the potential to explore pathogen genetic diversity on a scale that was previously unprecedented. However, there is a downside. The amount of data being generated is outstripping our ability to analyse it routinely, let alone carry out sophisticated evolutionary analysis. Particularly when it comes to pathogens, data sets could potentially be generated for which no suitable computational tools exist. This is exactly what happened in the case of the preliminary analysis in this project. HIV data was generated of importance to understanding drug resistance for which no software was available. This lack of software is because most research effort is being directed at assembling single complete genomes from next generation sequence data. However, with pathogens the interesting questions concern the diversity of sequences or so-called 'ultra-deep' sequencing. As a consequence, in this project we propose to develop, reliable, easy to use software that will be generically useful for all types of pathogen data sets. This will involve exploiting both the error information that is intrinsic to the new technology sequencing platforms and our considerable knowledge of the pathogen systems that we wish to analyse. Combined, this will permit us to develop software that will be able to summarise the variation in a sample of sequences and that will provide confidence in the sequence changes observed. Just as importantly, our computer-based approach will permit the sophisticated analysis of properties of the data in the hunt for clues to understanding a pathogen's biology. We will use this software in conjunction with next-generation sequence data to provide a detailed insight into intra-host dynamics of RNA viral populations. Particular focus will be given to genome diversity when the selective landscape within the host is altered, for example following transmission between individuals, disease progression or the initiation/alteration of drug treatments. Additionally our approach will be generically applicable to a wide range of research areas where understanding genetic variation is key.",2021,2013,University of Edinburgh,133691.29,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",,2010 +C17766,BB/H012419/1,Understanding the evolution and diversity of viral pathogens using next generation sequencing technologies,"A main cause of animal and human disease are infectious agents such as viruses. In this project we wish to study the genetic material of these pathogens. Genetic material is encoded as ordered 'sequences' of nucleotides. This information determine a virus' biological properties and response to the host immune system and thus the success of veterinary or medical treatments, whether they are vaccine or drug-based. Until very recently pathogen genetic material was characterized using Sanger sequencing, a technique invented in the late 1970s. More recently new sequencing technologies have become available that permit extremely large numbers of sequence fragments, called 'reads', to be generated. Many are referring to this as a revolution in sequencing because it now permits small groups of researchers to tackle projects previously only possible at sequencing centres, while sequencing centres can tackle truly massive sequencing projects, for example, the initiative to sequence 1,000 human genomes. This introduces the potential to explore pathogen genetic diversity on a scale that was previously unprecedented. However, there is a downside. The amount of data being generated is outstripping our ability to analyse it routinely, let alone carry out sophisticated evolutionary analysis. Particularly when it comes to pathogens, data sets could potentially be generated for which no suitable computational tools exist. This is exactly what happened in the case of the preliminary analysis in this project. HIV data was generated of importance to understanding drug resistance for which no software was available. This lack of software is because most research effort is being directed at assembling single complete genomes from next generation sequence data. However, with pathogens the interesting questions concern the diversity of sequences or so-called 'ultra-deep' sequencing. As a consequence, in this project we propose to develop, reliable, easy to use software that will be generically useful for all types of pathogen data sets. This will involve exploiting both the error information that is intrinsic to the new technology sequencing platforms and our considerable knowledge of the pathogen systems that we wish to analyse. Combined, this will permit us to develop software that will be able to summarise the variation in a sample of sequences and that will provide confidence in the sequence changes observed. Just as importantly, our computer-based approach will permit the sophisticated analysis of properties of the data in the hunt for clues to understanding a pathogen's biology. We will use this software in conjunction with next-generation sequence data to provide a detailed insight into intra-host dynamics of RNA viral populations. Particular focus will be given to genome diversity when the selective landscape within the host is altered, for example following transmission between individuals, disease progression or the initiation/alteration of drug treatments. Additionally our approach will be generically applicable to a wide range of research areas where understanding genetic variation is key.",2021,2013,The University of Manchester,403932.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",,2010 +C17769,BB/V013866/1,Absolute quantification of SARS-CoV-2 proteins and their human targets for informing drug strategies and accelerating vaccine development,"Understanding how the SARS-CoV-2 virus is infectious and causes disease requires a deep understanding of how the infectious particle-the virus- assembles from its component parts, and can make copies of itself and then invade cells and humans. We plan to work out how its building blocks-its proteins in particular-are produced, in what form and how much of each is made. To do so, we will use a method that weighs a protein, and counts how many proteins are in a sample from cells infected with the virus. These numbers will inform strategies for vaccine development as well as offer a deeper understanding of how the virus forms. We will use a method called Multiple-Reaction-Monitoring Mass Spectrometry (MRM-MS) with protein standards which we will manufacture in our laboratory. This methodology allows to directly measure absolute protein concentrations in complex biological samples. Our approach has great scope for upscaling, because any drug and vaccine development could adopt and benefit from our methodology. We propose to produce bespoke labelled synthetic protein standards and measure the absolute SARS-CoV-2 proteome, including some post-translational modifications, of (i) the virion (likely 9 proteins); (ii) within infected human cell lines (about viral 29 proteins), (iii) including yet undetected proteins; (iv) alongside key human proteins (19 proteins) the virus interacts with and or are considered drug targets; (v) determine the antigen-antibody ratios following vaccination trials in mice and humans and (vi) provide said standards to other laboratories to enable them to conduct similar analytics.",2021,2021,Imperial College London,427923.09,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +C17770,BB/V013874/1,SARS-CoV-2 genetic diversity and stability in the presence of neutralising antibodies and antivirals,"We want to understand how the SARS-CoV-2 virus (which causes COVID-19) might mutate when it is placed under what is known as selective pressure. At the moment the virus is spreading around the globe and it is mutating relatively slowly. That is likely to be because nobody has any pre-existing immunity top the virus and we have limited effective drugs that target the virus and even the one drug we do have that targets the virus (Remdesivir) has not been widely used. Over time we anticipate that more and more people will become immune because they have had the virus or because they have had a vaccine. At the same time, we believe that drugs that directly target the virus will become available and more widely used. Once this happens the virus will find it harder to spread and cause serious disease and when that happens it is possible that the virus will begin to accumulate mutations that will help it to evade the drugs we have developed and the vaccines we have deployed. This project will recreate that kind of evolutionary pressure in the laboratory so we can understand what kinds of mutations might emerge or even if the virus is actually unable to mutate and that the vaccines being planned and the antiviral drugs being evaluated will be effective over many years.",2021,2021,University of Bristol,154513.57,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C17771,BB/W003368/1,CATH-FunVar - Predicting Viral and Human Variants Affecting COVID-19 Susceptibility and Severity and Repurposing Therapeutics,"SARS-CoV-2 has caused a pandemic resulting in millions of deaths worldwide and significant social and economic disruption. Although vaccine trials have been encouraging vaccines must be distributed globally and therapeutic interventions will be needed for some time. It is clear that some human populations are much more vulnerable to the disease. For example older men and black and Asian communities. The factors causing these differences are still unclear and whilst social, economic and cultural issues are likely to be important, genetic factors could also play a role. Furthermore, the biological mechanisms by which severe responses arise and increase morbidity are still not known. In this project we will analyse genetic variations (causing reside mutations in the proteins) in diverse human populations (e.g. gender, ethnicity, people with severe responses) and in SARS-CoV-2. We will use structural and evolutionary data to determine whether the mutations could affect binding between the virus and human proteins. Human proteins in which mutations do affect binding will be mapped to protein networks to identify biological pathways that could be affected. We have powerful tools for functionally annotating proteins and the pathway modules in which they operate. Our data will rationalise the impacts on disease severity and improve diagnostics for populations at risk. Finally, proteins in these pathways are likely to be effective drug targets and we will use our protein family data to identify or repurpose suitable drugs having low side effects. We will also analyse related coronaviruses to identify future risks. We have already established a website (https://funvar.cathdb.info/uniprot/dataset/covid) providing mapping of SARS-CoV-2 viral proteins, functional annotations and proximity of mutations to known/predicted functional sites. This is currently populated with preliminary pilot data. It will be extended to host interactors and provide information on pathways and repurposed drugs. Research Plan We will: (a) Classify 'human interactor' proteins interacting with viral proteins into CATH-FunFams to extract known or predicted structures and map variants (residue mutations) from different genders and populations onto these structures. (b) Perform FunVar analyses to identify mutations in human interactor and SARS-CoV-2 proteins likely to have functional impacts. (c) Map human interactors to a protein network to highlight biological processes implicated in host response and differentially affected between different genders/ethnicities (d) Identify human interactors which have clinically approved drugs or which map to FunFams from which clinically approved drugs can be repurposed. (e) Disseminate information via FunVar-COVID19 pages Our pipeline will detect diverse variants in different human populations, likely to be impacting functions and affecting Covid-19 response. It will also analyse available drug data to suggest possible therapeutics. Furthermore, our pipeline will be generic and will also be used to analyse other closely related coronavirus genomes that could pose future risks.",2021,2022,University College London,157308.9,Human Populations | Other,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2021 +C17772,BB/W003376/1,"Mapping the lipid envelope composition of SARS-CoV2 for reducing transmission, thrombosis and inflammation","Coronaviruses are enveloped viruses, like influenza, Herpex Simplex and HIV. Thus, they are surrounded by a lipid bilayer derived from the host cell, in this case oral/lung epithelia. Surprisingly little is known about coronavirus membranes. Old studies suggest that virions bud from the phospholipid (PL)-rich ERGIC membrane, unlike many other enveloped viruses which bud from the plasma membrane, this a high level of PLs is likely. Importantly, the envelope of the SARS-CoV2 virus has not been mapped. We successfully purified SARS-CoV2 virus from Vero cell cultures on sucrose gradients, validated purity by nanosight, and are analysing its lipid composition using established mass spectrometry protocols (Stanton/O'Donnell laboratories). We can detect common PL and the full repertoire is currently being mapped and quantified. However, this now needs to be extended using human patient virus isolates since the composition is predicted to depend on the host cell and its metabolism. Notably, how virus membranes vary dependent on the host is unknown. Virus will be isolated from saliva, sputum and BAL of hospitalised patients with COVID 19. We have already obtained BAL, and subglottic aspirates, from patients intubated on ITU, and isolated live virus with titres >104 PFU/ml. Saliva will be obtained from patients using infrastructure set up as part of our ongoing clinical trial (ISRCTN25647404). We have isolated virus from saliva (104 - 105 PFU/ml) from patients on our ward. Virally-infected epithelial cells can also be harvested from the nasal mucosa using direct brushing. We plan to obtain virus from asymptomatic students donating to our university testing centre (if samples are available at that time). Virus will be purified using sucrose gradient centrifugation (already validated using Vero-derived virus). Lipids will be extracted using a chloroform/methanol method before lipidomics as described below. As this is a pilot study, we will aim for 20 BAL and 50-100 saliva samples as first step. Ethical approval processes for observational studies are well established and we anticipate no problems. A second approach will be to analyse virus cultured in A549 (human alveolar epithelial cell line transfected to overexpress ACE2 and TMPRSS2). This can be manipulated through exposure to cytokines consistent with the inflammatory status observed in COVID19 (PMID:32302401,32353870, 32678432). This model will allow scale up of virus isolation, enabling in-depth mechanistic studies to be undertaken. Virus will be cultured in A549 (+ACE2/TMPRSS2). The impact of inflammation will be tested using cytokines known to be elevated in COVID19, to mimic inflamed airway cytokine storm. These will include: IL-1b, IL-2, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-17, IFNg, IFNg-inducible protein 10, monocyte chemoattractant protein 1 (MCP1), G-CSF, macrophage inflammatory protein 1a, and TNFa (PMID:32302401,32353870, 32678432). Two other cytokines of significant interest are IL-4/IL-13, known to play a key role in allergic lung diseases like asthma. IL-4/IL-13 will be tested +/- dexamethasone. Importantly, IL-4/IL-13 are inducers of procoagulant eoxPL generation in airway epithelia (PMCID:PMC5765418). It is therefore critical that we determine the impact these cytokines have on envelope composition, to determine how this may impact dissemination of bioactive lipids via the virion envelope. This will be conducted on in vitro and in vivo isolated virus and to complement this we will also analyse the subcellular membranes of A549 cells. Third, we will conduct a transcriptomic analysis of A549 cells during infection focusing on lipid metabolism. This will determine which lipid signalling pathways are utilised/hijacked by the virus to support replication (particularly PL synthesis), aiming to identify druggable targets for intervention based on interfering with the lipid",2021,2022,Cardiff University,813294.08,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C17773,BBS/B/03416,Nucleolar localisation of the coronavirus nucleoprotein and its role in cell cyle control,NA,2021,2007,University of Leeds,253804.48,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2004 +C17777,BBS/E/I/00000883,Role of the non-structural proteins encoded by gene 3 of infectious bronchitis coronavirus,NA,2021,2004,The Pirbright Institute,7378.82,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2001 +C17781,BBS/E/I/00001390,BBSRC-funded studentship: Analysis of the avian coronavirus Infectious Bronchitis Virus as a potential vaccine vector,NA,2021,2012,The Pirbright Institute,23666.08,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies,2008 +C17783,BBS/E/I/00001857,Studentship: Analysis of the function of infectious bronchitis virus accessory proteins-towards better vaccines,NA,2021,2017,The Pirbright Institute,40605.05,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2013 +C17785,C19-IUC-029,Establishing a rapid and scalable high-volume facility for Covid-19 testing,"Establishing a rapid and scalable high-volume facility for COVID-19 testing using a robotic testing platform able to perform reliable, high-throughput PCR-based testing at low cost.",2021,-99,UK Dementia Research Institute,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C17786,C19-IUC-048,Mapping the community response to COVID-19 in Wales,"The distribution of community support - anything from helping the neighbours with shopping or simply someone to chat to - is patchy, leaving it difficult for public or charitable organisations to target additional support in areas where it is most needed. Working in collaboration with Public Health Wales, the Bristol-based IEU team have developed a live map which quickly highlight areas that might be more vulnerable due to an imbalance between community support and community need.",2021,-99,University of Bristol,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C17787,C19-IUC-066,Contributions to COVID trials,Centre PIs are leading recruitment to the Recovery trial locally including recruiting directly from mental health services.,2021,-99,MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Clinical trials for disease management, +C17788,C19-IUC-078,African COVID-19 preparedness (AFRICO19),"Our project will enhance capacity to understand SARS-CoV-2/hCoV-19 infection in three regions of Africa (Kenya, The Gambia and Uganda) and globally. Building on existing infrastructures and collaborations, we will create a network to share knowledge on next generation sequencing (NGS), including Oxford Nanopore Technology (MinION), coronavirus biology and COVID-19 disease control.",2021,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Kenya | Gambia | Uganda,"Pathogen: natural history, transmission and diagnostics",, +C17789,C19-IUC-096,DECOVID (HGU & rapid data science response),"Involved in data analysis in the DECOVID project (incl Turing Institute and HDRUK), a collaboration that aims to use near real-time health data to allow researchers and clinicians to identify factors and generate insights that can lead to more effective clinical treatment strategies.",2021,-99,University of Edinburgh,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management", +C17790,C19-IUC-112,Prevention and Treatment for Covid-19 Assoiated Severe Pnuemonia in The Gambia: A randomized clinical Trial - Funded by UKRI,"The study intends to evaluate the efficacy of a  chosen drug in preventing progression to severe pneumonia, and to evaluate the efficacy of prophylactic chosen drug in preventing COVID19 infection among house hold contacts (both symptomatic and asymptomatic).",2021,-99,MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Gambia,Gambia,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase) | Prophylactic use of treatments", +C17791,C19-IUC-113,COVADIS: COVID-19 epidemic in West Africa: infection dynamics and diagnostic approaches - Funded by EDCTP,"The aim is to contribute to the COVID-19 response in West Africa by improving local diagnostic and surveillance capabilities. They will focus on Burkina Faso and The Gambia, which have respectively the highest and lowest incidence of disease in West Africa.",2021,-99,MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine,,Unspecified,Black,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Gambia,Burkina Faso | Gambia,Epidemiological studies,Disease surveillance & mapping, +C17792,C19-IUC-117,DECOVID (Harwell Institute),The Institute's Bioinformatics and Health Informatics teams are involved in the DECOVID project leading the data standardisation and validation work.,2021,-99,MRC Harwell Institute,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C17793,C19-IUC-200,The COVID-19 Genomics UK (COG-UK) Consortium,"Together with the Wellcome Sanger Institute, the University of Cambridge is leading the national COVID-19 Genomics UK (COG-UK) consortium, created to deliver large-scale and rapid whole-genome virus sequencing to local NHS centres and the UK government. Funded by a £20 million investment from UK Department of Health and Social Care (DHSC), UK Research and Innovation (UKRI) and the Wellcome Trust, COG-UK is an innovative partnership between NHS organisations, the four Public Health Agencies of the UK, and over twelve academic partners providing sequencing and analysis capacity.",2021,-99,MRC Cancer Unit,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C17794,C19-IUC-201,Supporting the NIHR COVID-19 BioResource to enable comprehensive and immunophenotyping of affected individuals,"The NIHR COVID-19 BioResource, part of the national NIHR BioResource, is recruiting a cohort of patients with suspected coronavirus infection to enable sample-based and data studies of COVID-19 disease, recovery and mental-health outcomes, and offer the opportunity for participants to be involved in future research studies. Biological samples from COVID-19 BioResource participants will be processed and analysed in specialist containment facilities in the newly opened Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID).",2021,-99,MRC Cancer Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Secondary impacts of disease, response & control measures",Immunity | Indirect health impacts, +C17795,C19-IUC-218,Cancer prevention after the COVID-19,"We know that viruses such as the human papilloma, Epstein-Barr and hepatitis C viruses can be involved in causing some cancer. This pilot study will use a new analytical platform (EpiGraphDB) and existing population health data to gain better understanding of whether corona-virus infections might impact on cancer aetiology.",2021,-99,University of Bristol,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts, +C17796,C19-IUC-231,COVID-19 Intervention Modelling for East Africa (CIMEA),"COVID-19 is a global threat to health, with many countries reporting extended outbreaks. To date, nine countries in Africa have recorded infections and it seems imminent that East Africa will have introductions and onward transmission. The SARS-CoV-2 virus, the aetiological agent of COVID-19, spreads rapidly which means that control will be difficult. National plans for dealing with this public health emergency will benefit from predictions of the expected rate, distribution and extent of spread in countries throughout the region, and on the likely impact and feasibility of isolation and contact tracing interventions.",2021,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Unspecified,,,,Uganda,,Epidemiological studies,Disease transmission dynamics, +C17797,C19-IUC-239,The Impact of Covid-19 and associated responses on people who use or have used substances,"To initiate a network learning cycle around Covid19's effects on the drugs field drawing on the Transdisciplinary Complex Adaptive System framework and provide rapid reports on issues experienced by people who use drugs, which can directly inform the evolving public health response and actions to safeguard health and improve wellbeing.",2021,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17798,C19-IUC-263,Studying the specificity of SARS-CoV-2 proteases,Understanding the activity and specificity of the proteases that are encoded in SARS-CoV-2 and their consequences for infection.,2021,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C17799,C19-IUC-274,Automated COVID symptom tracking in Parkinson's Disease,"The impact of COVID-19 is acutely pronounced on patients suffering from Parkinson's Disease (PD) The majority of the 130,000+ UK patients are elderly, can suffer from respiratory complications, anxiety and depression. We propose to accelerate the development of an at-home Parkinson's Diagnostic Device (PDD) addressing this need to assist neurologists in telemedicine examination of PD patients for remote monitoring and subsequent updating of medication plans accordingly.",2021,-99,UK Dementia Research Institute,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17800,C19-IUC-297,ITAC (INSIGHT-13),"Randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of hyperimmune IVIG for the treatment of adult patients hospitalised with COVID-19",2021,-99,MRC Clinical Trials Unit at UCL,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Clinical trials for disease management, +C17801,C19-IUC-327,Experiences of the COVID-19 pandemic and lockdown on participants in the Southampton Women's Survey,"The current COVID-19 pandemic has brought many challenges with implications for wellbeing and mental health.  Data are being collected about experiences of the COVID-19 pandemic and lockdown on participants in the Southampton Women's Survey.  Mothers in the study will be contacted by both e-mail and text message asking them to complete an online questionnaire covering issues including mental health, health behaviours, grocery shopping experiences and self-efficacy.  The study offspring of these women are currently aged 12-21 years and the mothers will be asked to forward a link where appropriate asking the offspring to complete a similar online questionnaire tailored to their age group.  The longitudinal information available on these participants, stretching back to prospective data collected before the mothers were pregnant, will enable greater understanding of influences on health and wellbeing during the pandemic.",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17802,C19-IUC-333,Treatment of COVID-19 with remdesivir in the absence of humoral immunity,"Nat Commun. 2020 Dec 14;11(1):6385. doi: 10.1038/s41467-020-19761-2. PMID: 33318491 The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.",2021,-99,MRC Toxicology Unit at the University of Cambridge,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C17803,C19-IUC-338,Preparation and evaluation of an inactivated COVID-19 vaccine at UVRI and COVAB institutions in Uganda,"Representative local and global SARS-CoV-2 virus will be isolated from patients swabs, propagated and cultured on ACE2 Vero cells to produce bulk virus stocks. Virus stocks will be inactivated using b-propiolactone and purified using various steps of chromatography to produce the pure vaccine product. Humanized ACE2 mouse will be immunized, and then challenged with varying doses of the most representative circulating strain of SARS-CoV-2. Immunized mice will be evaluated for safety, protection from disease/death, and for the elicitation of vaccine induced-cellular and humoral immune responses. Safety and vaccine.",2021,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Pathogen: natural history, transmission and diagnostics",Immunity | Pre-clinical studies, +C17804,C19-IUC-339,"Community surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and of coronavirus disease-2019 (COVID-19) in high risk and general populations.","Rigorous community surveillance for SARS-CoV-2 and COVID-19 in high-risk and general populations, together with an assessment of the impact of co-morbidities on outcomes.",2021,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Europe,,,,Uganda,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis, +C17805,C19-IUC-340,A mixed-methods observational study to assess the feasibility of conducting COVID-19 vaccine trials among healthcare workers in Uganda,"The aim of this study is to assess the feasibility of conducting COVID-19 vaccine trials among healthcare workers in Uganda. The specific objectives are:1) To assess willingness to participate in COVID-19 vaccine studies and associated factors among healthcare workers in Uganda; 2) To estimate the prevalence of underlying health conditions that are associated with poor COVID-19 outcomes among healthcare workers in Uganda; 3) To describe the knowledge, attitudes, and practices regarding infection with SARS-CoV-2 and COVID-19 vaccine research among healthcare workers in Uganda",2021,-99,MRC/UVRI and LSHTM Uganda Research Unit,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel | Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,"Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Disease pathogenesis | Vaccine/Therapeutic/ treatment hesitancy, +C17806,C19-IUC-351,Support and strengthen the public health and socioeconomic systems to reduce the impact of the Covid-19 pandemic in The Gambia,"To support the Government of The Gambia's response COVID-19 outbreak in clinical care of patients, laboratory testing, community sensitization and logistics",2021,-99,MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Gambia,Gambia,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions | Community engagement", +C17807,C19-IUC-353,(Theme 1) Testing of an RT-LAMP test for SARS-CoV2,Development of alternative methods for virus detection which provide results in shorter time and with easier preparation methods (e.g. simple incubation at 65C in a heat block or water bath). Such methods would be invaluable to those in resource-poor settingsbut require clinically validation before being used in screening programmes.,2021,-99,Francis Crick Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C17808,C19-IUC-354,(Theme 2) The role of antibody in COVID-19 disease: distinguishing disease enhancing and prtective immune responses.,"The emergence of rare but debilitating conditions associated with SARS-CoV-2 - including Paediatric Inflammatory Multisystem Syndrome (PIMS) or Kawasaki disease (KD) - has raised concern that antibodies may enhance disease. In this project, researchers aim to assess how cross-reactive antibodies against other coronaviruses cause severe disease, how do antibody responses differ between patients with asymptomatic/mild infections and severe disease and how antibodies influence the rest of the immune response.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C17809,C19-IUC-355,(Theme 2) Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers (SAFER Study),"Hospital transmission of SARS-CoV-2, particularly within/by Healthcare Workers (HCWs) is a major public health concern. To evaluate these risks, we enrolled 200 patient-facing HCWs from the SARS-CoV-2 Acquisition in Frontline Healthcare Workers-Evaluation to inform Response (SAFER) study, a prospective cohort study in high-risk frontline HCWs in an acute National Health Service hospital trust in London. Through a series of regular swab and blood tests we were able to show almost half of HCWs showed evidence of carrying the infection at least once during the assessment period.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C17810,C19-IUC-356,(Theme 2) Immune correlates of disease in Covid-19,"The COVID-ImmunoPhenotyping project (COVID-IP,London) uses flow cytometry analysis of blood cells and circulating immune markers to better understand how the immune system responds to COVID-19 infection and if immunophenotyping can provide diagnostic information about disease severity. The earliest results from this study imply prognostic value for immunophenotyping IP10 plasma and T cytopenia in coronavirus patients which may aid in identifying those at risk of developing more severe disease.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C17811,C19-IUC-357,(Theme 2) COVID-19 Pulmozyme clinical trial plan,"Building on existing work microbial sepsis, researchers are designing clinical trials to test the efficacy of monoclonal antibody-mediated and biological therapy for cytokine-induced severe COVID disease, with promising results. Similarly, as histones are highly pro-inflammatory and become a central driver of these cytokines researchers at the Crick have initiated a human trial to treat COVID-19 with anti-histone Pulmozyme (DNase I). In parallel, studies of systemic fungal infection which share the major pathogenic mechanisms with virus induced sepsis may also have links not only with the cytokine storm but importantly with immune dysfunction whose origins remain unknown.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C17812,C19-IUC-358,(Theme 3) Cause and effect in receptor binding specificity associated with transfer between host species,"This study investigates the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. Using a range of structural biology techniques, such as Cryo-EM, to determine how viruses physically differ is invaluable to not only determine how SARS-CoV-2 binds to human ACE2 receptors but how disruption to its structure can destabilise the virus, opening opportunities to identify potential treatments.",2021,-99,Francis Crick Institute,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C17813,C19-IUC-359,(Theme 3) Tissue-specific and interferon-inducible expression of nonfunctional ACE2 through endogenous retrovirus co-option,"Angiotensin-converting enzyme 2 (ACE2) a human cell receptor targeted by the SARS-CoV-2 virus for entry into the cell. ACE2 has recently been proposed to be iduced by interferon and that SARS-CoV-2 may exploit this phenomenon to enhance viral spread. Crick researchers have identified a newly discovered isoform variant of ACE2 which is highly responsive to interferon stimulation, in stark contrast to canonical ACE2, also appears unstable and unable to bind SARS-CoV-2. The differences in physiology between these isoforms has implications for both interferon treatments of COVID-19 and virus transmission.",2021,-99,Francis Crick Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C17814,C19-IUC-360,(Theme 3) Predicting clinical trajectories of disease progression in SARS2-COVID19 on the basis of high-throughput plasma proteomics and maching learning,Analysis of patient blood samples provides information about disease progression and the opportunity to identify new biomarkers and therpeutic targets for COVID-19. However the process of sampling can often be slow. Proteomic high throughput analysis of patient sera will provide additional biomarkers for stratification of patients. In collaboration with the Coronavirus Clinical Characterisation Consortium (ISARIC 4C) at Edinburgh University and the Charite Hospital (Berlin) Crick researchers are developing newly designed high-throughput mass spectrometry-based platforms to obtain unbiased information about disease progression and distinctions between patients with severe and moderate Covid-19 disease.,2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom | Germany,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C17815,C19-IUC-361,(Theme 3) SARS-CoV-2 Enzymology,SARS-CoV-2 is a (+) strand RNA virus encoding a polyprotein which is cleaved into 16 separate non-structural proteins (Nsp). Nine of the 16 proteins are enzymes and represent obvious candidates for small molecule inhibitors. These enzymes are highly conserved and essential for viral growth. Our aim is to validate these biological targets for therapeutic use using a small molecule validation set of FDA approved small molecules. We will explore both repurposing of existing drugs and discovery of new leads targeting these enzymes to develop new therapies.,2021,-99,Francis Crick Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C17816,C19-IUC-362,(Theme 3) SARS-CoV-2 exit strategies,"The lifecycle of a virus requires release from infected cell through host cell membranes co-opting the host's own pathways for secretion. In the case of SARS-CoV-2 this budding is driven via the ESCRT pathway. We propose to perform a yeast 2-hybrid screen to generate tagged versions of SARS-CoV-2 structural proteins which will enable their visualisation during particle assembly and will allow us to use proteomic approaches to identify host proteins governing their membrane trafficking itineraries. We hope also to develop particle release assays for SARS-CoV-2. In doing so, we hope to understand more about late stages in the SARS-CoV-2 lifecycle.",2021,-99,Francis Crick Institute,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C17817,C19-IUC-364,(Theme 5) Anti-cancer therapies and COVID-19,"Projects within this theme aim to understand the specific risks for vulnerable populations, including the interaction of SARS-CoV-2 infection with different types of cancer and with specific treatment modalities. It will address: the impact of underlying health conditions, the impact of anti-cancer interventions on the course of COVID-19 and protecting vulnerable populations in hospital.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management", +C17818,C19-IUC-385,"Genetics, risk factors and COVID-19","How can we answer questions of causation (""what if?"" questions) when we can't perform experiments directly? In the case of COVID-19, a typical causal question would look like this: what would happen if we prescribed people anti-inflammatory medications? Would it improve outcomes? While we can answer these questions definitively by performing a randomized trial, this approach is slow. With this outbreak, time is of the essence and there are many potential treatments to evaluate. Instead of performing the randomization ourselves, our approach is to exploit a randomization that nature has provided for us in genetics.",2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments | Therapeutic trial design, +C17819,C19-IUC-386,"Elucidating the interplay between mitochondrial dynamics, membrane contact sites and SARS-CoV-2 viral infection driving inflammation","The last decade has witnessed repeated emergence of RNA viruses with high pathogenic potential in humans including SARS-CoV-2, Zika virus, yellow fever virus and Ebola virus. The inflammatory response to infection is a major driver of pathogenesis, but the molecular mechanisms by which these viruses initiate and dysregulate inflammation are not well defined. Mitochondria have emerged as critical regulators of the immune system and inflammation, serving as both signaling platforms and as sources of danger-associated molecular patterns (DAMPs) to initiate diverse signaling pathways. SARS-CoV-2, like other positive stranded RNA viruses, uses membranes derived from the ER for their replication factories, but also actively manipulates mitochondria, Golgi apparatus and other membrane bound organelles for replication purposes. However, it is unclear why mitochondria are hijacked during viral replication, and what are the consequences of this manipulation to inter-organelle communication and inflammation. In this project, in collaboration with Pr. Sonja Best (NIAID/NIH), we will use different SARS-CoV-2 infection models coupled to cutting-edge microscopy analysis to determine novel ways in which mitochondrial membrane remodelling and organelle contact sites are controlled and the importance of these events as drivers of inflammation.",2021,-99,MRC Mitochondrial Biology Unit,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis", +C17820,C19-IUC-387,Understanding and modelling COVID-19 mortality and severity using Electronic Health Record data: An observational cohort study,"We are using data from Addenbrookes' electronic health record to understand, model and predict the in-hospital course of COVID-19",2021,-99,MRC Biostatistics Unit,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C17821,C19-IUC-388,Estimating antibody seropositivity in Sweden,0,2021,-99,MRC Biostatistics Unit,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,Sweden,"Pathogen: natural history, transmission and diagnostics",Immunity, +C17822,C19-IUC-389,A2B-Covid,Analysis of COVID-19 transmission in hospital. We have produced an app to detect potential transmission events from patient and HCW data.,2021,-99,MRC Biostatistics Unit,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C17823,C19-IUC-390,Immune recovery from COVID-19 ,"This research aims at understanding the persistent immune dysregulation observed in patients with COVID-19 infection, in terms of its mechanistic basis, the risks it poses, and the therapeutic options to mitigate those risks.",2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C17824,C19-IUC-391,Early phase Radiotherapy trial for COVID patients,The purpose of this study is to document the feasibility and tolerability of low dose thoracic radiotherapy in patients with WHO level 5 COVID 19 infections.,2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation | Secondary impacts of disease, response & control measures","Disease pathogenesis | Supportive care, processes of care and management | Indirect health impacts", +C17825,C19-IUC-392,Platform trial for prophylactic treatments in care homes (PREVENT),"This is a large ""platform"" trial that will test several treatments intended to reduce the spread of COVID-19 within care homes, and reduce the risks of hospitalisation and death. A trial platform allows multiple treatments to be tested in parallel with results analysed regularly.",2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase), +C17826,C19-IUC-393,Longitudinal proteomic profiling of high-risk patients with COVID-19,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non- hospitalised ESKD patients with COVID-19 (n=256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. 203 proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3) and epithelial injury (e.g. KRT19). Machine learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Disease pathogenesis | Supportive care, processes of care and management", +C17827,C19-IUC-394,"Analysis of factors associated to hospitalisation times/rates in COVID patients in Spain (with the University of Valladolid, Spain)","Modelling of probabilities of hospitalisation and ICU in Castiile and Leon, Spain",2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Spain,Spain,Clinical characterisation and management,Disease pathogenesis, +C17828,C19-IUC-395,Analysis of the effect of COVID in cancer treatments in Addenbrooke's,Description of rates of oncological patients who had a change or delay of treatments in Addenbrooke's,2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17829,C19-IUC-396,Predicting recruit for treatment trials on COVID in the UK,Analysis of a multicentre prospective observational cohort study of patients admitted to hospital with laboratory-confirmed COVID-19,2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Therapeutic trial design, +C17830,C19-IUC-397,Nowcasting COVID-19 deaths,"Understanding the trajectory of the daily numbers of deaths in people with CoVID-19 is essential to decisions on the response to the CoVID-19 pandemic. Estimating this trajectory from data on numbers of deaths is complicated by the delay between deaths occurring and their being reported to the authorities. In England, Public Health England receives death reports from a number of sources and the reporting delay is typically several days, but can be several weeks. Delayed reporting results in considerable uncertainty about the number of deaths that occurred on the most recent days. We have developed a Bayesian model for estimating the number of deaths per day in each of five age strata within seven English regions.",2021,-99,MRC Biostatistics Unit,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C17831,C19-IUC-400,Tracking hospital transmission events,Reconstruction of transmission networks for the retrospective analysis of hospital transmission events,2021,-99,MRC Biostatistics Unit,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C17832,C19-IUC-401,Within-host evolution in an immunocompromised patient,Identify patterns of potential escape from therapy in a long-term infected immunocompromised host,2021,-99,MRC Biostatistics Unit,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C17833,C19-IUC-403,UK Biobank SARS-CoV-2 Antibody Study,"UKB intends to send out antibody tests to all 500,000 participants in Q1 2021. These lateral flow tests will identify whether participants have antibodies to SARS-CoV-2 within about 15 minutes. Participants will inform UK Biobank of their result so that we can make these data available to researchers to investigate the long-term health effects of infection across the full disease spectrum, such as ""long-covid"".",2021,-99,UK Biobank,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences, +C17834,C19-IUC-404,UK Biobank SARS-CoV-2 Imaging Study,"UK Biobank will use the data from the home-test lateral flow devices (that identifies whether individuals have antibodies to SARS-CoV-2) to invite participants back for a repeat imaging scan. This repeat imaging study aims to include up to 1,500 participants who have positive antibodies and 1,500 who are negative to enable research into the effects of SARS-CoV-2 on internal pathophysiology (such as the heart, lungs, brain) by enabling research to compare MRI data before and after infection.",2021,-99,UK Biobank,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C17835,C19-IUC-405,Exploring Inequalities in COVID-19 in Scotland,"During the Covid-19 pandemic, research in England has identified certain groups in the population, who have been more adversely affected by Covid-19, both in the risk of infection and the risk of severe illness and death. Individuals in minority ethnic groups and those living in more deprived areas have been identified as at higher risk of Covid-19. The evidence of such patterns in Scotland is limited, but more research is required. Our research aims to explore the risk of Covid-19 in these groups in the Scottish population. The findings of our research will be used to inform healthcare planning and policy in Scotland.",2021,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C17836,C19-IUC-406,Understanding the impacts of income and welfare policy responses to COVID-19 on inequalities in mental health: a microsimulation model.,0,2021,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions, +C17838,C19-IUC-408,"Investigating incidence, severity and risk factors for COVID-19 in BAME and Migrant groups to inform public health action - LINKED TO MR/V028375/1",0,2021,-99,MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow,,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Internally Displaced and Migrants | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C17839,C19-IUC-409,BRACE (UK): BCG Vaccination to reduce the impact of COVID-19 in healthcare workers,"From the Centre website: The BRACE trial aims to recruit 10,000 healthcare workers who work in a healthcare setting or have face-to-face contact with patients in the UK, Australia, the Netherlands, Spain, and Brazil. The results of this trial will help us find out whether, in current and future novel viral outbreaks, BCG vaccination could be used as an early intervention to protect healthcare workers and other high-risk groups. In the UK, the trial is a collaboration between Exeter Medical School's Clinical Trials Unit and the Murdoch Children's Research Institute (MCRI) in Melbourne, Australia. Professor John Campbell, Professor of General Practice and Primary Care here in University of Exeter is the principal investigator in the UK for the BRACE trial, with Professor Adilia Warris, Co-Director of the MRC Centre for Medical Mycology and Professor in Paediatric Infectious Diseases, as deputy principal investigator.",2021,-99,University of Exeter,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe | Western Pacific,,,,United Kingdom,United Kingdom | Australia | Netherlands | Spain | Brazil,Clinical characterisation and management,"Supportive care, processes of care and management", +C17841,C19-IUC-413,Prevalence of SARS-CoV-2 infection in UK,"20,000 volunteers recruited who agreed to provide finger-prick blood sample every month for 6 months and complete symptom survey. First results published in July. Now extending to all 500,000 UK Biobank participants using lateral flow tests during Q1 2021. Will also be used as recruitment frame for imaging study selecting 3000 people with and without evidence of prior Covid to assess effects of SARS-CoV-2 on major organs.",2021,-99,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis, +C17842,C19-IUC-414,"Does COVID-19 affect the brain? Gaining mechanistic insight ""in vitro"" on how brain cell function is disrupted upon exposure to serum from COVID-19 patients with neurological symptom","1]: for this study, to serum collected during hospitalization from a cohort of N=36 non-intensive therapy unit (ITU) COVID-19 patients, with and without delirium at admission. We will then identify inflammatory and neurogenic pathways underpinning the effects of the serum on cell proliferation, differentiation and apoptosis, proposing novel therapeutic targets for patients with COVID-19-delirium and possibly with other neurological and cognitive symptoms. Finally, results from this study will inform a planned grant application on neurological and cognitive follow-up of COVID-19-infected patient.",2021,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C17843,C19-IUC-417,Modelling of neurotropic SARS-CoV2 infection with human iPSC-derived vagus neurons,This study is designed to test if the vagus nerve is a pathway for infection of the central nervous system with the COVID-19 virus,2021,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C17844,C19-IUC-418,Effect of SARS-CoV-2 on fetal brain development,Histological examination of human fetal brain tissue for SARS-CoV-2 and it's effect on brain development.,2021,-99,MRC Centre for Neurodevelopmental Disorders at King's College London,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C17845,C19-IUC-537,Estimating a Time-to-Event Distribution from Right-Truncated Data in an Epidemic: a Review of Methods,"Time-to-event data are right-truncated if only individuals who have experienced the event by a certain time can be included in the sample. For example, we may be interested in estimating the distribution of time from onset of disease symptoms to death and only have data on individuals who have died. This may be the case at the beginning of an epidemic. Right truncation causes the distribution of times to event in the sample to be biased towards shorter times compared to the population distribution. We have reviewed statistical methods that deal with this bias, particularly in the context of CoVID-19.",2021,-99,MRC Biostatistics Unit,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease surveillance & mapping, +C17846,C19-IUC-421,Epidemiological investigation of risk factors associated with being positive for SARS-CoV-2 antibodies among healthcare workers at Addenbrooke's Hospital,0,2021,-99,MRC Biostatistics Unit,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C17847,C19-IUC-423,The international arm of the Teenagers' Experiences of COVID-19 (TEC-19),"The current COVID-19 pandemic is creating conditions unprecedented in living history including worldwide restrictions on people's movement. Adherence to movement restrictions is likely to profoundly affect young people's sense of well-being, their diets and physical activity levels and their mental health. As a group, adolescents are likely to be affected in specific and long-lasting ways by this disruption to their normal lives. Adolescence is a period for the formation of identity and development of autonomy. It is also when diet and physical activity habits are formed. This moment in global history provides us with a unique opportunity to explore over time the impact of major disruption on young people, their psychological development and health behaviours. The international arm of the Teenagers' Experiences of COVID-19 project expands on the UK TEC-19 study (lead by MB and SS) to include our partners in South Africa, Ghana, Ethiopia, India and Canada. Focus group discussions with young people are being used to explore how the pandemic is affecting the lives, mental health and well-being, and eating habits and physical activity behaviours of young people living in both rural and urban settings across sub-Saharan Africa (Ethiopia, Ghana, South Africa) and India, and two provinces in Canada.",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Africa | Americas | South-East Asia,,,,United Kingdom,South Africa | Ghana | Ethiopia | India | Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17848,C19-IUC-425,Southampton Phase 2 Pilot Programme Educational Materials: supporting student engagement in reducing COVID-19 transmission through saliva-based LAMP testing in asymptomatic populations,"Phase 2 of the DHSC-funded Southampton pilot programme for use of saliva-based LAMP testing in asymptomatic populations included 'piloting systems for application of regular testing in schools serving vulnerable communities and other major mixing events in the education sector'. As part of this, highly successful pilot education and engagement materials for both primary and secondary school students have been designed and delivered in the schools by our LifeLab scientific literacy team. The Phase 2 Educational Materials (P2EM) programme enables us to undertake development and evaluation of these pilot education materials, to help shape and co-create a COVID-19 focussed science for health literacy programme for primary and secondary school",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C17849,C19-IUC-426,Development of a Hampshire & Isle of Wight COVID-19 Testing Hub,"Through joint working between University Hospital Southampton NHS FT (UHS FT), the University of Southampton (UoS), local government and the wider NHS and social care, the aim of this proposal is to establish a sub-regional Hampshire & Isle of Wight (HIOW) COVID-19 testing and training hub as a pathfinder for a national program. The objective is to demonstrate how mass scale Direct RT-LAMP saliva testing can be operationalised in a sub-regional testing hub driven by the NHS in service delivery. Developing a model through collaborative partnership with both commercial and academic partners, the constant focus will be on the need to create an infrastructure that delivers to the sub-regional population, while being easily and rapidly scaled up across the country. As a demonstration site, the aim is to immediately commence testing 2,000 samples per day from the outset, ramping up to 100,000 samples per day over 2-3 months.",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Health Systems Research | Research on Capacity Strengthening",Diagnostics | Health service delivery | Systemic/environmental components of capacity strengthening, +C17850,C19-IUC-427,Understanding evidence pathways and government decision-making in response to Covid-19: a multi-country comparative analysis,"In the face of Covid-19, governments globally have been making urgent and difficult decisions. Yet in spite of the apparent uniformity of threat, and the almost universally proclaimed adherence to scientific guidance, their responses have diverged. Government responses have ranged from the negation or minimisation of the threat and reliance on individual behavioural modification, to stringent population-wide restrictions of movement, employment and education, as well as everything in-between. What is behind the diversity? How are different governments framing the problem and what elements are they prioritising in response to local conditions? Do the institutional settings of different jurisdictions present impediments or advantages in their respective responses? Which domains of expertise are governments engaging to help them come to decisions and shape responses?",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions, +C17851,C19-IUC-428,Investigate links between novel MRI cardiac phenotypes and risk of COVID-19 infection,"In the subset of UK Biobank participants who have detailed cardiac magnetic resonance imaging data available, we are investigating whether CMR phenotypes at baseline associated with increased risk of coping 19 infection. We have elucidate a relationships with particular markers, which may help inform understanding of links between covid19 and cardiac health.",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis, +C17852,C19-IUC-429,Rapid evidence review of role of vitamin D in COVID-19 prevention and treatment,"We have undertaken a comprehensive review of the current evidence base relating to vitamin D levels and supplementation for the prevention/treatment of respiratory disease, in particular COVID 19 infection. We conclude that there is insufficient evidence to make any recommendations and that intervention studies are needed.",2021,-99,MRC Lifecourse Epidemiology Unit at the University of Southampton,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C17854,C19-IUC-432,REACT,The CTU is working on a meta-analysis of treatments for Covid-19 in collaboration with the WHO as part of the Rapid Evidence Appraisal for COVID-19 Therapies (REACT) working group.,2021,-99,MRC Clinical Trials Unit at UCL,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management", +C17855,C19-IUC-434,Dynamo,This is a project run by Prof Charlotte Bolton Nottingham to look at brain MRI responses to exercise in long covid patients using in bore exercise,2021,-99,MRC Versus Arthritis Centre for Muskuloskeletal Ageing Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences", +C17856,C19-IUC-439,Rational design of a new range of Covid-19 nanobodies to generate first line therapies effective against new variants. Jim Naimsith. Rosalind Franklin Istitute and Protein Production UK,,2021,-99,Research Complex at Harwell,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C17857,C19-IUC-444,Effect of SARS-CoV-2 on fetal brain development,This project is investigating the impact of Sars-CoV-2 infection on human fetal brain development.,2021,-99,MRC Centre for Reproductive Health at the University of Edinburgh,,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis, +C17858,C19-IUC-445,(Theme 3) G2P-UK: A national Virology Consortium to address phenotypic consequences of SARSCov-2 genomic variation. Funded by UKRI MRC,The Crick will provide clinical isolates and animal models as part of the national Virology Consortium.,2021,-99,Francis Crick Institute,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Disease models, +C17859,C19-IUC-455,Investigating genetic overlap between severe Covid manifestation and susceptibility to Alzheimer's disease,"Our studies on the genetic code in people with Alzheimer's disease have identified several genes that are associated with an increased risk of developing Alzheimer's. These genes function in the immune cells of the brain, and research by us and others is currently testing exactly how these genes alter the function of these immune cells in people that develop Alzheimer's. Recent work has shown that at least one of the Alzheimer's risk genes we identified also determines whether an individual will also show critical illness with COVID-19. Our work therefore suggests that inheriting a common variant of this gene called OAS1 can increase the risk of developing both Alzheimer's disease and a severe response to COVID-19. Our current research is investigating the function of this OAS1 gene in different immune cell models. Understanding how this gene functions will allow us to predict better which people will develop Alzheimer's later in life and a severe response with COVID-19. Our work will also lead to the development of drugs and therapies to reduce the severity of these diseases, and also to lessen the neurological problems associated with COVID-19.",2021,-99,UK Dementia Research Institute,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies, +C17860,C19-IUC-456,"Associations of COVID-19 risk perceptions with mental health, wellbeing and risk behaviours","Researchers at the Universtiy of Bristol will use newly collected data in the Avon Longitudinal Study of Parents and Children(ALSPAC) to investigate the risk perceptions around the COVID-19 pandemic on mental health, wellbeing and risk behaviours.",2021,-99,University of Bristol,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Indirect health impacts, +C17861,C19-IUC-457,Modelling pooling strategies for SARS-CoV-2 testing in a university setting,"Researchers at the University of Bristol have used mathematical simulations to test different COVID-19 testing strategies in a university population. They found that when positive cases are clustered by a know social structure such as a student household, pooled sampling (where a household pool their swabs into a single test) is most efficient.",2021,-99,University of Bristol,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions, +C17862,C19-IUC-458,"Pandemics and 'infodemics': the nature, extent and reach of public health misinformation on social media during the COVID-19 pandemic","This project will use Twitter data, aiming to uncover the nature, extent and reach of misinformation on social media about the use of face-coverings during the COVID-19 pandemic.",2021,-99,University of Bristol,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication, +C17863,C19-IUC-459,Impact of the COVID-19 pandemic on health care workers and the health care system in Zimbabwe (ICAROZ),"Frontline health care workers in Zimbabwe are pivotal to the COVID-19 response, as they are responsible for setting up rapid testing and communication to help prevent transmission in the community. This project will support the health care workers by putting in place occupational health services such as testing, contract tracing and screening for causes of illness and death among the workforce.",2021,-99,MRC Integrative Epidemiology Unit at the University of Bristol,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Zimbabwe,Zimbabwe,Infection prevention and control,IPC in health care settings, +C17864,C19-IUC-460,SARS-CoV-2 infection at the human animal interface,"CVR researchers, working in collaboration with colleagues at the University of Glasgow's School of Veterinary Medicine, are investigating the contribution of cats as a potential reservoir for SARS-CoV-2 and the risk of reverse zoonosis. This project aims to improve our understanding of the evolution of SARS-CoV-2 in cats and to determine the zoonotic potential and virulence of SARS-CoV-2 viruses isolated from cats.",2021,-99,MRC-University of Glasgow Centre for Virus Research,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission, +C17865,C19-IUC-461,SARS-CoV-2 point of care diagnostics,"CVR researchers, in collaboration with University of Glasgow and external colleagues, are supporting the development and testing of a range of point of care diagnostics for SARS-CoV-2.",2021,-99,MRC-University of Glasgow Centre for Virus Research,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C17866,C19-IUC-462,Fundamental biology of SARS-CoV-2,CVR researchers are engaged in a range of projects aiming to understand the fundamental biology of SARS-CoV-2. Projects include understanding how SARS-CoV-2 and other coronaviruses manipulate enzymatic activites inside cells and the role of RNA-binding proteins during SARS-CoV-2 infection.,2021,-99,MRC-University of Glasgow Centre for Virus Research,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history", +C17867,C19-IUC-464,Immune responses to SARS-CoV-2,CVR researchers are leading projects designed to inform our understanding of the immune response to SARS-CoV-2. The CVR is also one of 17 partners in the UK-CIC consortium.,2021,-99,MRC-University of Glasgow Centre for Virus Research,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C17868,C19-IUC-465,Understanding SARS-CoV-2 in Malawi,"General population serosurveillance in low-income Africa is fundamental to understanding thepopulation exposure to SARS-CoV-2, to explain the observed epidemiology and to ensure that ongoing control measures in the region are proportionate and are not guided by observationsfrom very different settings. Detailed longitudinal immunological studies of infected individuals will be key to determining the long-term strategy in managing COVID-19 in highly vulnerable African populations.",2021,-99,MRC-University of Glasgow Centre for Virus Research,,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Malawi,Malawi,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures, +C17869,C19-IUC-466,SARS-CoV-2 infection at the human animal interface,"There is an urgent need to improve our understanding of the factors governing cross-species transmission of coronaviruses. This timely and important proposal aims to understand the molecular factors that both limit and facilitate the emergence of novel coronaviruses in human populations, and to identify other coronaviruses that could emerge with pandemic potential.  ",2021,-99,MRC-University of Glasgow Centre for Virus Research,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations", +C17870,C19-IUC-467,REACT-GE: Multi-omics to identify biological pathways underlying severity of SARS-CoV-2 infection - PI Prof Paul Elliott,"This study aims to address some of the major gaps in our understanding of SARS-CoV-2 infection and disease, in particular with respect to differences in disease susceptibility, severity of infection and disease mechanisms. We will apply a multi-omics approach to mild/asymptomatic cases, to identify biological pathways that are protective of or deleterious to the response to SARS-CoV-2 infection.",2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C17871,C19-IUC-469,CO-CONNECT - COVID - Curated and Open aNalysis aNd rEsearCh plaTform,"The CO-CONNECT project brings together 29 different UK organisations to create a single information resource linking 44 cohort, serology and other health and non-health data sources on SARS-CoV-2 in the UK.",2021,-99,"Imperial College London, King's College London",,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom | United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C17872,C19-IUC-470,ONS D+18269:18278ata Con+F18278+182+18269:18278,"This project aims to characterise and quantify the biological, social and environmental drivers of medium-term health outcomes following infection with SARS-CoV-2, by linking healthcare, REACT and environmental data.",2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C17873,C19-IUC-471,COVID 19 RESPONSE,"This project includes a series of studies on the etiology of SARS-CoV-2 infection and on testing and surveillance technologies, to help identify at-risk populations and inform infection control measures.",2021,-99,"Imperial College London, King's College London",,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control",Diagnostics | Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities, +C17874,C19-IUC-473,SCAMP-COVID19: a school-based cohort study of COVID-19 secondary impacts on mental health,"This project will investigate the impacts of the COVID-19 pandemic and public health measures on adolescent mental health and wellbeing, amongt a large adolescent cohort SCAMP (Study of Cognition Adolescents and Mobile Phones).",2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts, +C17875,C19-IUC-474,Long-term exposure to air-pollution and COVID-19 mortality in England,"Recent studies suggested a link between long-term exposure to air-pollution and COVID-19 mortality, so this project will build on that hypothesis by factoring in localised air-pollution patterns, which can be an overlooked confounding factor in such analyses.",2021,-99,"Imperial College London, King's College London",,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity, +C17876,C19-IUC-475,Estimating weekly excess mortality at sub-national level in Italy during the COVID-19 pandemic,"This is the first subnational study on excess mortality during the COVID-19 pandemic in Italy, one of the worst-hit countries. We predicted the weekly mortality rates at municipality level for 2020 based on the modelled spatio-temporal trends (i.e. in the absence of the pandemic) and estimated the excess mortality and the uncertainty surrounding it.",2021,-99,MRC Centre for Environment and Health,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,Italy,Italy,Epidemiological studies,Disease surveillance & mapping, +C17877,C19-IUC-476,Exposure to air pollution and COVID-19 incidence∶ a multi-country study,"In this collaborative study with the University of Toronto (Canada), we investigate whether long-term average exposure to air pollution (PM2.5 and NO2) increases the risk of COVID-19 infection in Canada, England, Italy and the United States.",2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Americas | Europe,,,,United Kingdom | United Kingdom,Canada | United Kingdom | Italy | United States of America,Epidemiological studies,Disease susceptibility, +C17878,C19-IUC-477,Joint Biosecurity Centre,"Our goal is to estimate the prevalence of COVID-19, combining several sources of data and integrating two different type of information on the number of cases: direct estimates (such as randomized surveys and testing programs) and indirect estimates (such as hospital admissions).",2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics, +C17879,C19-IUC-478,Risk factors for positive and negative COVID-19 tests using UK biobank data,"Analysis of UK Biobank data identifying risk factors for testing positive or negative for SARS-CoV-2 infection up to 18 May 2020, as well as those discriminating test positive vs test negative individuals using a test negative design approach.",2021,-99,"Imperial College London, King's College London",,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,Epidemiological studies,Disease susceptibility, +C17880,C19-IUC-481,Children's Health in London and Luton (CHILL): impact of London's Ultra Low Emission Zone on brain development in schoolchildren,This study within the CHILL cohort aims to examine the impact of Sars-Cov-2 infection / air pollution changes (both policy and lockdown driven) on the cognitive development of children.,2021,-99,"Imperial College London, King's College London",,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts, +C17881,C19-IUC-482,Measuring population-level health & activity in a global pandemic by wastewater-based epidemiology,"Measuring SARS-CoV-2 and pharmaceuticals in urban wastewater using mass spectrometry, to accurately monitor large population activity in near-real time.",2021,-99,"Imperial College London, King's College London",,Viruses | Environment | Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics, +C17882,C19-IUC-484,"Perceptions of air pollution, health and COVID in BAME communities",This study's aim is to investigate vulnerable and minority ethnic groups' perceptions of the relationship between air pollution and health and how this relationship has been impacted by the coronavirus (COVID-19) crisis.,2021,-99,"Imperial College London, King's College London",,Human Populations,Other,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom | United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C17883,C19-IUC-486,Obesity and COVID outcomes,,2021,-99,MRC Metabolic Diseases Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C17885,C19-IUC-489,Software development,This project focusses on development of research software to support COVID-19 outbreak response and cuts across all other projects,2021,-99,Imperial College London,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems, +C17886,C19-IUC-491,Multimerised sub-unit vaccines,The project is designed to determine whether multimerised protein (subunit) SARS-CoV-2 antigens make them better vaccine candidates.,2021,-99,MRC Laboratory of Molecular Biology,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Pre-clinical studies, +C17887,C19-IUC-492,(Theme 3) COVID-19 molecular mechanisms and target identification,SARS-Cov-2 recruitment of haem metabolites to evade antibody immunity,2021,-99,Francis Crick Institute,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity", +C17888,C19-IUC-495,Slum Health: Arresting COVID-19 & Improving Well-Being in Urban Informal Settlements - 5 April 2020,"Dr Tolullah Oni of our Global Public Health Research programme was part of an international team of reseachers that pre-published a set of practice and policy recommendations that aim to dampen the spread of COVID-19, improve the likelihood of medical care for the urban poor whether or not they get infected, and provide economic, social and physical improvements and protections to the urban poor that can improve their long-term well-being.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts | Economic impacts, +C17889,C19-IUC-496,School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review - April 2020,"Researchers including Dr Oliver Mytton undertook a systematic review of published and pre-published studies to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks They conclude that school closures have much less impact on the spread of these viruses than other social distancing interventions, and recommend that policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and consider combinations of social distancing measures.",2021,-99,MRC Epidemiology Unit,,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C17890,C19-IUC-497,Analysis of NHS health records of 3.8 million adults yields estimate of COVID-19 mortality according to underlying conditions and age - May 2020,"An analysis published by a team of scientists that includes Unit researcher Dr Claudia Langenberg and colleagues at UCL, University College London Hospitals NHS Foundation Trust, and Health Data Research UK, indicates that at least 20% of the UK population has a high-risk underlying condition for COVID-19 infection listed by Public Health England. The authors have created a publicly accessible COVID -19 risk calculator showing how age, sex and underlying health conditions can affect mortality rates in different scenarios. They write that the analysis, which used NHS health records from 3.8 million adults in England, shows that the UK government must ensure that measures to ease the lockdown take into account this clinical vulnerability.",2021,-99,MRC Epidemiology Unit,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C17891,C19-IUC-498,NIHR video appeal for people from BAME backgrounds to take part in COVID-19 Research - May 2020,"Professor Nita Forouhi of our Nutritional Epidemiology programme helped to organise, and featured in, a video appeal by the National Institute for Health Research (NIHR) for more people from Black, Asian and minority ethnic (BAME) backgrounds to take part in COVID-19 research studies. Alongside Professor Forouhi the video featured British actors, comedians and broadcasters Omid Djalili and Sanjeev Bhasker, and American Oscar winning actor Whoopi Goldberg, as well as Professors Kamlesh Khunti and Azhar Farooqi from the University of Leicester. The appeal was shared widely on social media, with the Omid Djalili's twitter video viewed more than 125,000 times, and was reported in more than two hundred local and regional UK print and online news outlets.",2021,-99,MRC Epidemiology Unit,,Other,Asian | Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Research | Community engagement, +C17892,C19-IUC-499,OneDraw feasibility study launches - June 2020,"Social distancing measures and new ways of working mean that new methods of blood sample collection are urgently needed for Unit studies. In preparation for a large-scale surveillance study in the Fenland cohort to determine the prevalence of previous infection with COVID-19, a study has been launched to evaluate a self-applied blood collection using a device called OneDraw. It is important that we obtain adequate blood samples from participants using the dried blood spot (DBS) method that can be standardised as far as possible to undertake the COVID-19 serological testing repeatedly over a 6-month period.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease surveillance & mapping, +C17893,C19-IUC-500,Recruitment starts for SWiM-C: Supporting Weight Management during COVID-19 - June 2020,"Recruitment has started for the Supporting Weight Management during COVID-19 (SWiM-C) study, which seeks to evaluate whether a new online self-help programme is better than standard advice at helping people to prevent weight gain and supporting good physical and mental health. SWIM-C is recruiting 360 adults adults (aged over 18 years) with overweight or obesity and access to weighing scales at home.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts, +C17894,C19-IUC-501,COVID-19 and ethnicity: who will research results apply to? - June 2020,"In June Professor Nita Forouhi was an author on the Lancet Comment article ""COVID-19 and ethnicity: who will research results apply to?"".",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities", +C17895,C19-IUC-502,Sentiment and opinion analysis of public space physical activity in Lagos during lockdown - June 2020,"Research has started on a Cambridge Africa Alborada COVID emergency call award: Sentiment and opinion analysis of public space physical activity in Lagos during lockdown: a data-driven approach to developing context-aware public health messaging to reduce disease vulnerability and improve COVID-19 control. This project is led by Tolu Oni from our Global Public Health Research programme, and is a collaboration with Associate Professor Taibat Lawanson at the University of Lagos Centre for housing and sustainable development and Associate Professor Camaren Peter at the Graduate School of Business and Centre for Analytics and Behavioural Change at the University of Cape Town. This project aims to conduct opinion analyses of public space leisure physical activity to explore perceptions of government lockdown restrictions (and enforcement), and the impact of these lockdown measures on the perceptions, nature and frequency of appropriation of public space for activity in Lagos. Findings will inform development of context-aware public health messaging that safely encourages physical activity in the short term and health foresight interventions to reduce co-morbidity-associated vulnerability to future health emergencies long-term.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Nigeria,Nigeria,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts, +C17896,C19-IUC-503,Genetic architecture of host proteins interacting with SARS-CoV-2 - July 2020,"A team led by Unit researcher Dr Claudia Langenberg has published in Omicscience summary statistics for large-scale genomic and plasma proteomic data from over 10,000 individuals to characterise genetic architecture of host proteins reported to interact with SARS-CoV-2. This accompanies the submission of the paper ""Genetic architecture of host proteins interacting with SARS-CoV"" which is available on BioRxiv. The summary statistics freely available without restrictions, and include an interactive matrix and annotations for all protein targets and cis-associated genetic loci, as well as interactive tables with pGWAS summary statistics for individual SNPs, genes, or genetic regions from which results can be sorted, filtered, and exported.",2021,-99,MRC Epidemiology Unit,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity, +C17897,C19-IUC-504,Earlier lockdown restrictions linked to greater reduction in new COVID-19 cases - July 2020,"A BMJ paper by Dr Nazrul Islam and colleagues - including senior author Professor Martin White at the MRC Epidemiology Unit - examines the association between implementation of physical distancing interventions and new cases of COVID-19 in 149 countries and regions. Their findings show that physical distancing measures, such as closing schools, workplaces, and public transport, restricting mass gatherings, and restrictions on people's movement within countries or regions ('lockdown'), were associated with an overall reduction of 13% in new COVID-19 cases in a study period of up to 30 days after implementation of the measures. The data also shows that implementing physical distancing measures earlier was associated with a greater reduction in new cases, and that in combination with school and workplace closure, restriction on mass gatherings seemed to be a key component associated with a decrease in COVID-19 incidence.",2021,-99,MRC Epidemiology Unit,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C17898,C19-IUC-505,"Unit launches study to monitor COVID-19 in 12,000 Cambridgeshire residents - July 2020","Participants in Cambridgeshire's Fenland Study are being invited to join an innovative study that will use a home-administered blood sampling device - the Drawbridge Health OneDraw device - to find out how many have evidence in their blood of previous COVID-19 infection. The primary aim of this study is to quantify the proportion of people who have had COVID-19 in the Fenland cohort, and participants will be tested several times over the duration of the study allow researchers to identify new as well as existing COVID-19 cases. Researchers will also be able to determine if those with COVID-19 antibodies at the start of the study continue to have positive antibody status over the study period, or if antibody levels decline over time. The study will also investigate whether it is possible to identify the COVID-19 pre-symptomatic phase using measurement of signs and symptoms collected via a smartphone App developed by Huma. Participants will use a smartphone app to record measurements such as heart rate, heart rate variability, respiratory rate, blood oxygen, and temperature. Participants will also enter health information such as body weight and diet changes, medication and supplement use, their mental health and wellbeing, and COVID-19 symptoms and potential risk factors.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease surveillance & mapping | Disease pathogenesis, +C17899,C19-IUC-506,Vitamin D for COVID-19: a case to answer? - September 2020,"In a comment article in the Lancet Diabetes & Endocrinology, Unit scientist Professor Nita Forouhi and Professor Adrian Martineau of the Blizard Institute discuss the available evidence for a role for Vitamin D in preventing or treating COVID -19 infection. They note that current evidence is inconclusive and recommend population-based trials investigating vitamin D supplementation as a means of reducing the severity of COVID-19. In meantime they urge measures to ensure that people achieve recommended daily amounts of Vitamin D (10 micrograms per day for adults in the UK) saying this ""might also reduce the impact of COVID-19 in populations where vitamin D deficiency is prevalent; there is nothing to lose from their implementation, and potentially much to gain.""",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management", +C17900,C19-IUC-507,Research helps NHS support people with diabetes during coronavirus - September 2020,"MRC Epidemiology Unit Director Nick Wareham has contributed to recent research that is being used to help the NHS offer greater support to those with diabetes. The research, published in in two papers in Lancet Diabetes and Endocrinology shows that people living with diabetes face a significantly higher risk of dying with COVID-19. A third of deaths in England are associated with the condition. As a result of this research, the NHS in England has called on people with diabetes to access help available to them, including a new dedicated helpline and online tools to help manage the condition during the outbreak.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis, +C17901,C19-IUC-508,Quarterly report on progress to address COVID-19 health inequalities - Race Disparities Unit - October 2020,"Dr Raghib Ali was announced as a one of the Government's new expert advisers on COVID and ethnicity on 22 October, and with Professor Keith Neal of the University of Nottingham briefed science journalists at a Science Media Centre on the Government's Race Disparities Unit's first quarterly report on progress to address COVID health inequalities, with particular reference to ethnicity. Dr Ali explained how understanding of risk factors has improved since the Public Health England report in June, and described the action government has taken to date and outline future steps to address disparities.",2021,-99,MRC Epidemiology Unit,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts, +C17902,C19-IUC-509,Consortium led by Unit researchers develops open platform to help discover COVID-19 drugs - December 2020,"An international consortium led by MRC researchers has developed an open access platform to help prioritise drug discovery and repurposing efforts for the current COVID-19 pandemic. The platform provides information on the genetic variation of host proteins involved in SARS-CoV-2 infection, based on analysis of genetic and proteomic data from 10,708 Fenland Study participants.",2021,-99,MRC Epidemiology Unit,,Human Populations,White,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Prophylactic use of treatments, +C17903,C19-IUC-510,Crick COVID-19 NHS Vaccination Centre,"The Crick has established its own COVID-19 NHS vaccination centre with a capacity of 1,000 people a day, seven days a week.It will be staffed by more than 300 researchers and staff volunteers and was set up within a matter of weeks.",2021,-99,Francis Crick Institute,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,, +C17904,C19-IUC-512,Therapeutic targeting of necroptosis cell death pathways in COVID-19 ARDS: proof-of-principle,"Abstract: SARS-CoV-2, which causes Coronavirus Disease 2019 (COVID-19), is the third highly pathogenic coronavirus that has led to significant global infections in humans. Acute respiratory distress syndrome (ARDS) is accompanied with alveolar epithelial and pulmonary capillary endothelial damage, myeloid cell influx and excessively high levels of circulating proinflammatory cytokines. Although the mechanisms of pathogenesis are unclear, data from work on SARS and ARD associated with sepsis point towards hyper-inflammation, activation of RIPK3-driven necroptosis and inflammasome-driven interleukin (IL)-1β/IL-18 cytokine production. Here we will investigate these processes in human endothelial and myeloid cells infected with SARS-CoV2 and test clinically-approved RIPK3 and inflammasome inhibitors in preventing necrotic cell death and release of inflammatory cytokines. In addition, examine the temporal profile of necrosis and necro-inflammation in patients with the severest form of COVID19.",2021,-99,MRC Centre for Molecular Bacteriology and Infection at Imperial College London,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies, +C17905,C19-IUC-513,TracK- Transmission of Coronavirus in Kids,"To refine our understanding of COVID-19 transmission and predict impact of different public health interventions, we have adapted an existing study of scarlet fever transmission in schools, to understand more about  transmission of SARS-CoV2 between children and between children and adults.  In contrast to adults, syndromic surveillance for COVID-19 in children is not helpful, as disease is largely asymptomatic. Sequential intensive testing of oral/nasopharyngeal samples is the ideal method to quantify or rule out transmission events, since we do not at present know if seroconversion is a reliable marker of exposure in asymptomatic children.   Exploiting statutory notification systems, the study will explore the events that follow when a child is diagnosed with SARS-CoV2, both in the child, the environment around the child, and their contacts from school, and at home. Through a sequence of individual school cohort studies, we are using intense longitudinal sampling of children and the environment to address the following questions :1. Do symptomatic or asymptomatic children transmit the virus to each other or to adults in schools or household? Or are adults more likely to be the source of infection in children? 1. Do symptomatic or asymptomatic children transmit the virus to each other or to adults in schools or household? Or are adults more likely to be the source of infection in children?",2021,-99,MRC Centre for Molecular Bacteriology and Infection at Imperial College London,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C17906,C19-IUC-514,Discovery and validation of transcriptional signatures to distinguish COVID-19 and other viral infections from bacterial sepsis in adults,"Novel approaches to discriminate likelihood of bacterial and viral infections are required to support antimicrobial prescribing decisions and infection control practice, and, with the advent of COVID-19 new diagnostic challenges arise. Building on an existing and actively recruiting infection bioresource, we aimed to derive and validate a blood transcriptional signature to differentiate bacterial infections from viral infections including COVID-19.   Blood RNA sequencing was performed on a discovery cohort of emergency department adult patients with confirmed bacterial or viral infection. Differentially expressed host genes were analysed to derive a discriminating signature of genes that could differentiate the groups. We  developed a simple RT-qPCR test for genes in the signature and validated the signature of a new six-month prospective cohort of patients presenting with undifferentiated fever and then on a second case-control cohort of COVID-19 and bacterial infection patients. ",2021,-99,MRC Centre for Molecular Bacteriology and Infection at Imperial College London,,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C17907,C19-IUC-515,Immunologic and Transcriptomic Comparison of Patients with COVID19 and other Infection at Point of Admission  ,"In contrast to intensive care research, there is a paucity of research in the field of acute infection, as patients do not present at predictable times and either rapidly get better or, rarely, die from infection; the BioAID bioresource was set up to address this gap. BioAID continued to recruit samples throughout the first wave of COVID19 admissions (current total ~900 since March 2020) providing a valuable resource of  'time zero' RNA and serum samples and negative control/non COVID19 samples. The aim of this project is to compare the cytokine and transcriptomic profiles of patients admitted with COVID19, with those admitted with bacterial sepsis and other viral infections, in order to provide context and better understanding of COVID19 pathogenesis. We hope that the transcriptomic data may also serve to enhance any new diagnostic signatures for COVID-19 infection. The samples and data will also  support the validation of prognostic biomarkers for the national ISARIC-4C cohort of COVID-19 patients",2021,-99,MRC Centre for Molecular Bacteriology and Infection at Imperial College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease pathogenesis, +C17908,C19-IUC-516,Theme 2 - the role of antibodies in Covid infection,"The Legacy Study will utilise a unique bank of over 400,000 coronavirus samples at the Crick, gathered as part of the institute's testing partnership with many north London healthcare facilities, including UCLH. Scientists and clinicians will aim to understand the coronavirus and how it behaves in individuals - how the virus is transmitted between people, how later stages of the disease develop and how the body's immune system attempts to control the virus. ... ""With informed consent, samples will be matched with individuals to establish how factors like age, sex, ethnicity, and past and current medical histories, impact the risk of infection. Participants will also be invited to give regular swab and blood samples over two years, to better understand how emerging variants and vaccination affect risk of infection and how the body responds."" - from Crick news article August 2021.",2021,-99,Francis Crick Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease susceptibility", +C17909,C19-IUC-517,Theme 2 - the role of antibodies in Covid infection,"In their study, published in eLife (29 July), the scientists analysed blood samples collected from patients who had previously been infected with COVID-19 and who were admitted to UCLH for other reasons, samples from health care workers as well as samples collected from patients at different points earlier in the pandemic. They identified COVID-19 antibodies in the blood, and in the lab ran tests to see if antibodies produced after infection with one variant were able to bind to and neutralise other variants. ... ""As the antibodies were able to bind to other variants at a similar level, but had differing ability to neutralise other strains, this suggests that there are only a few regions on the spike of the virus which are important to this neutralisation process. It is the mutations within these key sites which impact the ability of antibodies produced by one variant to neutralise another."" - from Crick news article August 2021.",2021,-99,Francis Crick Institute,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity, +C17910,EP/W001411/1,COvid-19 Transmission Risk Assessment Case Studies - education Establishments,"Schools are planning to re-open in September and with the recent increased awareness of airborne transmission of Covid-19, there is an urgent need to monitor the situation and to provide guidance on ventilation best practice. This is emphasised by the expected onset of cooler weather when there will be a conflict between maintaining high fresh air ventilation flows and energy consumption and occupant comfort. We will quantify the risk of airborne COVID-19 transmission in schools and evaluate the effectiveness of mitigation measures, by developing techniques to assess the absolute risk of infection in a given indoor space, using field studies in primary and secondary schools, complemented by laboratory experiments and CFD to elucidate the flow patterns responsible for airborne transport. The understanding generated will underpin recent developments in infection modelling to predict the likelihood of airborne transmission within schools. The project will reduce the uncertainties associated with airborne transmission routes and provide evidence to evaluate mitigation measures. The scenarios we will investigate include changes to ventilation, use of screens, classroom lay-out and occupancy profiles. The methodology will facilitate application to offices, restaurants, shops etc. Airborne infection occurs through re-breathed air, the concentration of which can be directly inferred from measurements of CO2. Indoor flow is strongly affected by the locations of windows or vents, the heat rising from occupants/equipment and disturbances caused by people movement. Thus, accurate representations of these processes in the laboratory and CFD are needed to interpret the monitoring data currently collected in schools, which are typically single point measurements.",2021,2022,University of Cambridge,1085594.08,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2021 +C17911,EP/W010836/1,Rapid air and surface disinfection using dry hydrogen peroxide,"We have formulated a catalyst capable of generating gas phase H2O2 (or dry hydrogen peroxide (DHP)) in significant concentrations (Akram et al. Chem. Sci., 2016, 7, 5833) using very dilute hydrogen concentrations of H2 in air at ambient temperature. Sub ppm levels of DHP are known to be highly effective in disinfecting airborne pathogens and two companies (Synexis and CASPR; https://synexis.com/; https://casprgroup.com/ ) have commercialised devices for disinfecting air with DHP procured and synthesised non-catalytically. We now propose an innovative catalytic approach. Our innovations in liquid phase H2O2 synthesis (Europe 17728642.4; 14753141.2; 16704892.5; US 9340423) has proven enhanced disinfection is achieved when H2O2 is synthesised using a catalyst. Simultaneous to H2O2 production, highly reactive short-lived oxygen species are also formed, and results in improved pathogen kill by over a million-fold compared to commercial H2O2 alone. We consider that a similar enhancement will result from a catalytic approach to DHP formation. We aim to utilise this discovery to design a novel catalysed route to DHP to disinfect air and surfaces in occupied spaces. We will use electricity to electrolyse water to produce low concentrations of hydrogen which is subsequently reacted with air over the gold-palladium catalyst producing gaseous DHP in such a way that all the hydrogen is totally consumed. The aim is to continually generate DHP at sub ppm levels (a maximum of 1ppm (1.4 mg H2O2 / cubic meter) of H2O2 averaged over a 8 hour period is allowed) and introduce this into flowing air that will disinfect both the air and surfaces. While the immediate focus is tackling the current Covid-19 pandemic the project aims to tackle the longer term and ongoing need for continuous air and surface disinfection for a range of pathogens",2021,2022,Cardiff University,259498.83,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C17912,ES/W001330/1,COVID BAME highlight: A collaborative approach to understand and remediate the impact of COVID19 on mental health in BAME communities: A pilot study,"The COVID19 Pandemic has exacerbated societal differences, with its greatest negative impact on vulnerable groups, including people from a BAME background. Among other challenges, this population, and especially children and young adults, experiences mental health difficulties to a greater degree than people from white background and faces significant difficulties in accessing mental health services. This project will use a collaborative approach that will involve members of BAME communities, including people with mental health difficulties, mental health professionals and members of charities. The project aims are: (1) to better understand the impact of COVID-19 on mental health and service access in families of children/young adults from BAME backgrounds using qualitative methods, and (2) to evaluate the feasibility and acceptability of an online carers' skill-based training to improve mental health wellbeing in families from BAME backgrounds. It is acknowledged that there is great heterogeneity among BAME communities and therefore this pilot study will focus on adults of black ethnicity, with the longer-term goal of replicating findings in other ethnic minority groups. The output of aim 1 will be improved knowledge about the effects of COVID19 on mental health among adults of black ethnicity. The output of aim 2 will be the understanding of how an online carers' skill-based training could be adapted to the needs of this population to promote mental health wellbeing in families.",2021,2022,King's College London,310939.17,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C17913,ES/W001349/1,Sharing the diagnosis of dementia in the post-Covid clinic: patient and practitioner perspectives,"With the COVID-19 pandemic, most memory clinics switched to remote consultations (by telephone or video-call) to continue to meet the needs of patients while minimising the risk of anyone becoming exposed to the virus. However, there is a significant lack of clarity around how a dementia diagnosis should be delivered remotely and how the person with dementia experiences this process. The aim of this research is to understand experiences of delivering and receiving a dementia diagnosis during COVID-19 through the exploration of emotional impact, practical impact, and ethical considerations. This project will be co-produced by the researchers and a small group of people living with dementia and their care partners (up to eight people). This group will be consulted at each stage of the research. About 30 people who have recently been patients at memory clinics since services shifted to remote working (in March 2020) will be interviewed as well as a similar number of professionals who have been delivering diagnoses. These interviews will be analysed with the group mentioned above to identify recurring themes. These themes will then be used to inform an online national forum. Findings from both this online discussion and the interviews will be used to develop a briefing document for policymakers and a guideline for clinicians about how best to deliver a remote dementia diagnosis. Additional outputs will include podcasts to engage the public and academic papers in open access, peer-reviewed journals.",2021,2022,University of Edinburgh,233391.54,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C17914,ES/W001535/1,Farming resilience: civil society's role in supporting vulnerable rural communities through and beyond the COVID-19 pandemic,"The experience of a pandemic at a time of rural change (the post-Brexit agricultural transition is the biggest change to rural policy in a generation) presents a range of unique challenges to farmers, rural communities and the civil society organisations that support them. The project seeks to: i) understand the success of different activities in limiting the 'scarring' effects of the COVID-19 pandemic on farmers' mental health and resilience ii) understand the impacts of the pandemic on civil society organisations themselves (including severe fundraising shortfalls, operational restrictions and social challenges) and iii) scale up these understandings to build system and community resilience against future shocks, such as the impending challenges presented by the post-Brexit agricultural transition. It will do this through a scoping review, surveys and interviews with civil society organisations, and a range of policy and practice workshops with a range of stakeholders, supported by established partnerships and a strong steering committee. This research is important because we know very little about how the farming community, and the support systems underpinning them, are being affected by COVID-19. Our deliverables will enable policy-makers and organisations to support the levelling up of rural communities and to increase their community resilience to future challenges.",2021,2022,University of Reading,259641.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Farmers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Indirect health impacts | Social impacts | Economic impacts | Cross-cutting,2021 +C17915,ES/W001756/1,The COVID Cohort Study,"How has the COVID-19 pandemic affected socioeconomic inequalities in life chances, in terms of short-term effects on educational attainment and well-being, and long-term educational and career outcomes? This study will provide immediate findings to this and related research questions about the impact of the pandemic on educational inequality by SES, gender and ethnicity by designing, analysing, reporting on, and archiving two annual waves of a high-quality new cohort study of pupils in year 11 in academic year 2020-21 across England. This brand new resource will collect data from pupils, parents and schools, augmented with administrative data from DfE's NPD and other sources. Moreover, it will provide the start of a long-term resource for the research community to explore medium/long-term effects as participants move into further and higher education, and the labour market (with planned LEO consent questions). Led by Dr Jake Anders, with Professor Lindsey Macmillan and Dr Gill Wyness (UCL CEPEO), Professors Lisa Calderwood and Alissa Goodman (UCL CLS) and Carl Cullinane (Sutton Trust), with Kantar as lead fieldwork agency, the team combines world-leading expertise in educational inequalities, social mobility, analysis of longitudinal data, and the design and management of cohort studies. Our bid is supported by key stakeholders, including DfE, ADR UK, EEF, TASO, OfS, and HEAT to ensure co-production of policy-relevant evidence. This study will fill an important gap in understanding of the medium and long term effects of COVID-19 on young people completing their education and moving into the labour market at this unprecedented time.",2021,2022,University College London,3654835.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2021 +C17916,ES/W002086/1,Learning through disruption: rebuilding primary education using local knowledge,"This project is intended to inform public debate on how the monies committed to the Education Recovery fund (so far £1.3 billion) can best be used to support pupils in primary schools in the aftermath of the pandemic. The Education Recovery Commissioner is working to an open brief with the declared intention that ""decisions on catch-up should be locally-led, but supported by the evidence"" (Schools Week, 2021). Although the need to invest in education is clear (Sibieta, 2021; EEF, 2020), quantitative studies cannot yet advise on exactly where and how recovery monies should be spent. Early evidence includes reports of bounce-back and unexpected gains for some pupils (Kuhfeld et al 2020); while interventions designed to ""catch-up"" small target groups of students performing below expected levels in normal times may not be appropriate or easy to scale-up in these exceptional circumstances (NAO, 2021). This project will bring new evidence to bear on the local dimensions to recovery planning through context-sensitive case studies, using a purposive sample to explore how the most pressing issues in recovery are identified in a diversity of schools and the responses they lead to. Our previous research on COVID demonstrates that school catchments influence schools' actions during a period of disruption (Moss et al, 2020). By purposively sampling primary schools working with different social catchments that faced a range of challenges during COVID, we will explore the local and multidimensional aspects of the pandemic's effects on education and their implications for the broader policy discussion on planning for recovery. We will do so by focusing on what each section of these diverse school communities has made of the experience of learning during the pandemic and assessing how this affects their priorities as schools return to something more like normal functioning. This matters as to date local dimensions to recovery planning have been largely overlooked in favour of very different forms of research which have garnered more publicity. In particular, media coverage has focused on large scale quantitative modelling of potential impacts that must at this stage remain speculative (EEF, 2020) and indeed, are prone to inciting moral panics (Forsyth, 2021). This may only distort government planning and distract from what schools might more sensibly do now. Policy driven in this way risks leading to a poor fit between ""solutions"" imposed from above, with too little regard for the supporting evidence (CCT, 2021), and actual conditions on the ground. Without sufficient fine-grained attention being paid to what is really appropriate locally, a great deal of money may in effect be wasted. To refocus attention on the local dimensions to post-COVID planning for recovery as schools reopen more fully, this project will: 1. explore schools' strategies for supporting pupil learning post-disruption, in response to their local circumstances and in dialogue with their immediate support networks 2. take account of the diversity of voices within the school community (staff, parents and pupils); the extent to which they converge or diverge on thinking about the consequences of this period of disruption for individual pupils; and whether they are reciprocally understood. 3. through comparison of similarities and differences in individual schools' priorities and strategies for the future, identify the role local knowledge should play in determining how recovery funding ought to be allocated and spent. In this way, the context-sensitive case studies planned for this project will bring evidence to bear on how local knowledge can contribute to a national strategy for rebuilding education, at a point when national decisions are still to be reached over how any recovery funds are spent. Findings will clarify how much discretion schools should be able to exercise in order to successfully meet local priorities and needs.",2021,-99,University College London,81220.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts, +C17917,ES/W003058/1,Limiting virus transmission during a Sporting Mega Event: COVID 19 and UEFA EURO 2020,"This research will add value by analysing, informing and evaluating COVID-19 measures and related behaviours around large sporting events. Our findings and consideration of mitigation measures in host countries both before and after the tournament will help to inform best practice, by generating new evidence in three areas: 1) venue set-up and operating procedures to mitigate COVID-19 transmission risks in large stadia; 2) approaches to engagement with and regulation of local hospitality stakeholders and fan zones (if operational) during SMEs including measures to mitigate transmission arising from supporter interaction and movement pre and post-match; and 3) understanding supporters' attitudes and experiences regarding mitigation measures during SMEs. Furthermore, we will examine the implementation of and adherence to measures in and around venues by local organising structures (LOS) across host countries. Our findings will be rapidly synthesised to enable other similar events planned for summer 2020 and beyond to learn from the EURO 2020 tournament.""",2021,-99,University of Stirling,279402.79,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement, +C17918,G0300354/1,Study of the T cell response in SARS,"A new illness causing fever, cough, pulmonary infiltration and respiratory failure was first recognised in Southern China (Guangdong and Hong Kong) in November 2003. The constellation of symptoms has subsequently been termed Severe Acute Respiratory Syndrome (SARS). Although the majority of cases reside in mainland China and Hong Kong the disease has now been identified in around 20 countries worldwide. The causative agent for SARS has been shown to be a virus belonging to the coronavirus family. This virus is related in sequence to other members of the coronavirus family which in humans is responsible for the common cold. Many questions about SARS pathogenesis remain to be answered and in addition there is an urgent need to investigate new treatments and the possibility of vaccine development. We propose to study T cell responses to infection with SARS virus in cohorts of infected patients recruited in China, Hong Kong and possibly Oxford if an outbreak occurs in our area. The essential question will be whether T cell immune responses to SARS are good or bad in the disease progression. Although T cell immunity plays an important role in controlling many virus infections, it may also, if unchecked, result in tissue damages and immunopathogenesis. Therefore, a fuller understanding of the pathogenesis of SARS infection and also the immunological correlates of immunity will be beneficial in terms of vaccine design and treatment.",2021,2004,MRC Human Immunology Unit,668215.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2003 +C17921,G0902430/1,"From bats to humans: the social, ecological and biological dynamics of pathogen spillover","Bats are increasingly being recognised as reservoir hosts for significant human pathogens: within the past 15 years, bats have been identified as the source of Hendra, Nipah, SARS, Ebola and Marburg viruses, amongst others, all of which are RNA viruses and all of which cause incurable diseases in humans with high case fatality rates. Bats also are the reservoir hosts of lyssaviruses, the rabies family of viruses, which are also zoonotic RNA viruses. In addition to being responsible for sporadic, but frequent, fatal human disease outbreaks on an annual or semi-annual basis, there is some evidence of bat RNA virus adaptations to the human host; in particular, henipaviruses have been highlighted as a possible future pandemic threat to public health. Although progress has been made on diagnostic techniques and on identifying the source wildlife species and populations of these viruses, the factors driving or facilitating zoonotic emergence, including bat to human transmission, are little understood. These factors are likely to be multiple, interrelated and complex, involving aspects of pathogen biology, host ecology and human behaviour. The catalyst grant will explore this multifaceted complexity through four key questions: the transmission dynamics of RNA viruses in identified bat populations; the population dynamics and behaviours of these bats; the dynamics of infection spillover from bats to humans and the dynamics of medical diagnosis and response. This investigation is necessarily multi-disciplinary and is divided into two phases. The first involves a review of the literature and the identification of missing disciplines and collaborators needed to build an integrative conceptual framework linking environmental and social dimensions with the modelling of infection dynamics. The second phase involves jointly-written literature reviews and critiques, preparatory work on new theoretical research questions and consultations with end-users in order to develop a comprehensive and holistic research consortium proposal. We will, therefore, use this catalyst grant to build a world-class multidisciplinary consortium of scientists, integrating pre-existing and new research activities in West Africa, South Asia and Australia, to develop a strong interdisciplinary research programme to investigate bat-human pathogen dynamics. This newly-formed consortium will be well positioned to advance the intellectual boundaries of current thinking on wildlife-to-human virus transmission by asking new theoretical, multi-disciplinary questions that more closely address social, environmental and medical interrelationships and complex realities.",2021,2011,University of Cambridge,64166.11,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2010 +C17922,MC_PC_19067/2,Spatial heterogeneity in transmission and the impact of interventions: a mathematical modelling approach,"This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Predicting the size and duration of potential COVID-19 outbreaks is an essential component of public-health planning and preparedness. Mathematical models of disease transmission are potentially powerful tools for predicting the course of an upcoming epidemic and evaluating control and mitigation strategies. However, standard models of disease transmission without population structure overestimate the speed of invasion of a novel pathogen. We have developed a spatial metapopulation transmission model for the UK that is grounded in demographic data which incorporates regular (commuter-like) movements of individuals. In previous work, we demonstrated that regular, repeated movements lead to slower epidemic spread. Adapting this model for COVID-19, we estimated that an uncontrolled epidemic in England and Wales would peak ~4 months following sustained person-to-person transmission, but that seasonality in transmission could substantially alter the timing and magnitude of the peak burden. Here, we propose to use this model to evaluate control and mitigation strategies for COVID-19. Guided by the World Health Organization-identified research priorities and PHE needs, we will estimate the impact of travel restrictions, border screening and quarantine policies. We will also assess the effects of social distancing measures and other non-pharmaceutical interventions on peak burden and epidemic timing and rank measures by effectiveness. The model will also be adapted to assess and rank pharmaceutical deployment strategies. Our vision is to make the model adaptable and available to other countries and settings, both with and without census and commuting data. Key challenges include modelling commuting patterns, incorporating realistic age structure, adding an observation model to capture morbidity and mortality and including behaviour change which could substantially alter dynamics.",2021,2021,University of Bristol,217617.29,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2021 +C17923,MC_PC_20031,COVID-19 Immunity - National Core Studies (IMM-NCS),"The 'NCSi4P' programme will determine how assessment and optimisation of immune function can accelerate control of the Covid-19 pandemic. NCSi4P will focus on the role of immunity in Prediction of outcome, Protection against infection and Prevention of re-infection. These will provide a legacy for future Preparation. Prediction research will define how immunogenetics and immune function, including memory to other coronaviruses, determines risk from SARS-CoV-2 infection. Comparisons will be made between ethnic groups and in patients with a cancer diagnosis to determine how optimisation of immune function may be supported. In Protection studies we will work with surveillance teams to study people with asymptomatic infection. The aim is to understand how the immune system can control infection and to contrast this with findings in severe disease. The potential role of the immune system in 'long-covid' syndromes will be studied. Prevention will determine how immune memory after infection is predictive of individualised risk of potential re-infection. The findings will be compared to data emerging from vaccine studies in order to guide optimal regimens. This will be complemented with studies to optimize laboratory assays of cellular immune function. The integration of these immune studies will support the UK in Preparation for future pandemics.",2021,2021,University of Birmingham,9694800,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C17924,MC_PC_20049,REACT Long COVID (REACT-LC),"The REACT-Long COVID (REACT-LC) programme aims to characterise the genetic, biological, social and environmental signatures and pathways, and their inter-relationships, that underpin progression to Long COVID, and to understand the natura lhistory and long-term sequelae post-SARS-CoV-2 infection. To identify people with persistent symptoms who have not been hospitalised, we will use a sampling frame generated through repeated random population surveys of SARS-CoV-2 prevalence in the community, the REACT programme, which includes >1.5 million individuals with documented SARS-CoV-2 status (RTPCRor lateral flow test), including >30,000 with positive tests, 90% of whom have consented to be re-contacted and 85% to data linkage.The research is to be delivered through five integrated work packages (WPs). WP1 will describe variations in experience of Long COVID and develop patient reported outcomes (PROMS) in consultation with expert collaborators and through our patientand public partners. We will use online focus groups, discussion forums, individual interviews, and surveys on the VOICEGlobal platform, and recruit a panel of people with Long COVID to provide input on their symptoms and experience. In WP2 we will carry out detailed clinical phenotyping on 8,000 people (4,000 with Long COVID); 2,000 will have repeat measures at 4-6 months including 400 for T-cell function. The WP2 samples will be used in WP3 which includes multi-omic analysis, brain and inflammatory biomarkers. WP4 will use data from surveys sent to 30,000 test-positive and 90,000 test-negative on RTPCR/lateral flow in REACT, plus linked health data, to explore the social and environmental determinants of Long COVID and its long-term sequelae. WP5 is the data analysis and integration to identify genetic, biological, social and environmental determinants of Long COVID. We aim to identify key biomarkers and biological pathways underlying Long COVID and possible drug targets, as well as inequalities and social determinants of variations in outcome.",2021,2024,Imperial College London,3660056.3,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences",2021 +C17925,MC_PC_20051,"Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care","Long-term health consequences of C-19 (long-COVID) occur frequently. Most infections are not hospitalised; population studies are the place to understand individual and societal challenges of long-COVID. We will address the following questions: 1. How do we define and diagnose the sub-phenotypes of long-COVID? 2. What are the predictors of long-COVID, and what are the mechanisms of the sub-phenotypes? 3. What are the long-term health (physical and mental), and socioeconomic consequences? What factors enhancerecovery? 4. What is the level of GP adherence to NICE diagnosis and management guidelines? Can a pop-up tool in medical records enhance adherence? We have an established consortium of experts and platforms uniting linked national primary care registries and population cohorts. The national coverage of primary care registries captures all individuals presenting to their GP, with linked prescribing,consulting, referral and outcome data. Many with long-COVID do not seek care. Population cohorts, with repeat C-19 related questionnaires, overcome this limitation. Further, the standardised pre-pandemic health data enables dissection of the effectsof infection versus progression of co-morbidity. Questionnaires will identify long-COVID cases across cohorts. A subgroup of 200 cases will be matched to three sets of controls (C-19 +, long-COVID-), (C-19-, long-COVID+), and (C-19-, long-COVID-). They will wear a device capturing exercise capacity, heart rate and respiration, and complete regular online questionnaires on mental health and cognition. They will attend clinic for imaging to assess target organ damage. Qualitative work with people with long-COVID will inform diagnostic criteria and understanding of the lived experience. Parallel analysis of cohorts and registries will address each question. With NICE, we will quantify adherence to diagnostic and management guidelines in GP records, and pilot a pop-up intervention to enhance adherence. Our findings will enhance diagnostic criteria, identify pathways for bespoke sub-phenotype intervention, and inform plans for health service delivery.",2021,2024,University College London,6459124.15,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Indirect health impacts",2021 +C17926,MC_PC_20054,"COVID19 Strategic Priorities: SUPPLEMENTARY FUNDING OFFER FOR THE MRC UNIT, THE GAMBIA AT LSHTM (MRC Unit, The Gambia)",The MRC is pleased to confirm additional funding from the Global Challenges Research fund for the MRC Unit. This award provides resource to support; ·         your unit in the efforts of managing the impact and activities during the COVID crisis ·         the procurement of and installation of oxygen concentrators,2021,2021,London School of Hygiene & Tropical Medicine,813143.27,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C17927,MC_PC_20058,Phase 1 COVID-19 Data and Connectivity - National Core Study (Phase 1 D&C-NCS),"The Data and Connectivity study sits across the other National Core Studies and delivers a national health data research capability to support COVID-19 research questions, ensuring datasets are discoverable and accessible and linkages are established to answer the priority research questions from the other five National Core Studies. Making data available for wider research use will increase the scope of benefits beyond the specific studies above, leading to unexpected benefits and boosting UK research capacity more generally, increasing return on investment for the NCS programme. Data integration and harmonisation of methods and standards will enable rapid research and development of new interventions and technologies across the spectrum of COVID-19, and knowledge and technology transfer to other clinical and public health areas. Collation and linkage between datasets is critical to bringing the core studies together, ensuring that each of them can deliver against their policy priorities e.g. hospital data may not currently be linked with GP data and wider community data (e.g. socioeconomic data or data on housing and the built environment). Access, cleaning, linkage and use of these datasets together is needed to fully understand links between these factors and outcomes. Delivery of the COVID-19 Data and Connectivity Study will involve close interaction with data custodians, the public and patients, and providers of UK-wide national Trusted Research Environments (TREs) to ensure the required data is stored safely and securely, made readily available to approved researchers and is associated with compute, analytical and data services that make it easier to address priority research questions in a transparent and trustworthy way. Phase 1 will: • Continue to respond to emerging COVID-19 research priorities, mapping key datasets required by the National Core Studies, NIHR UPH Studies and SAGE sub-groups to allow research which can inform policy and operational decision making across the UK • Further develop the data infrastructure and services across the UK to allow faster access to high priority health, administrative, molecular, and behavioural data assets for researchers working on the most important COVID-related studies, ensuring priority research questions can be answered efficiently, in a transparent and trustworthy way. • Strengthen and extend the existing national Trusted Research Environments (TRE) and UK Health Data Research Innovation Gateway infrastructure through inclusive four nations approach ensuring the priority datasets for COVID-19 research are findable, accessible, inter-operable and reusable (FAIR) as a single ""shop window""",2021,2022,Health Data Research UK,20399475,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2021 +C17928,MC_PC_20060,Phase 1 COVID-19 Immunity - National Core Study,"The magnitude and quality of the immune response remains a central determinant of clinical outcome following SARS-CoV-2 infection and vaccines now provide an approach for pandemic control. The National Core Study - Immunity (NCSi) programme in Phase 0 was designed to co-ordinate and build on UK investment in COVID-19 immunity and initiated a number of investments in 2020/21. These were based on four themes which seek to predict and manage individual risk, protect acute infection and late effects, prevent primary or re-infection and prepare for future pandemic challenges. In Phase 1, these will continue and comprise: PREDICT: 1. Centre for Cytokine Autoantibodies will interrogate serum sample collections, including those from the NCSi/UKB collaboration, to determine the clinical importance of antibodies against a range of cytokines in order to define clinical risk and develop new therapeutic opportunities. 2. DIRECT: Determining the Immune Response in Ethnic minority healthcare workers to COVID-19 infecTion will determine the importance of ethnicity in relation to immune response to natural infection and post-vaccination. 3. EVITE study of shielding efficacy through evaluation of NHS records, questionnaire responses and blood test results at 12 months after shielding and subgroups such as those with cancer, BAME or living in deprived communities. 4. Asymptomatic COVID19 in Education (ACE) Immunity Study will examine SARS-CoV2 across the (young) population to influence student/school movement policies PROTECT: 1. NCSi collaboration with UK Biobank will undertake detailed analysis of Covid-specific immune responses and cellular phenotype in a world-leading unique 3000 participant repeat-imaging study. 2. Understand Immune senescence and its impact on natural immunity and vaccine responses in the CAIRO vaccine cohort and associated studies of vaccine response in secondary immune suppression with chronic lymphocytic leukaemia that is seen in older people. PREVENT: 1. Next Generation Immune Assays will be commissioned to transform the sensitivity, specificity and logistics of serological and cellular assays. 2. Vaccine Responses: The OCTAVE study of immune monitoring after vaccination will be maintained and supported with further investment. Phase 1 investment circa £1.1m, 75% funded by UKRI and 25% funded by the Vaccine Task Force. For more details please see https://www.ukri.org/news/new-study-tests-third-jab-for-people-with-weakened-immune-systems/ 3. Re-infection, vaccine failure and viral Variants of Concern will comprise a portfolio of studies including an open commissioned call to determine mechanisms of inadequate immune protection in (re-) infection after natural or vaccine-induced immunity.",2021,2022,University of Birmingham,10563730.11,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified | Other,Health Personnel | Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2021 +C17929,MC_U137881015,Immunopathogenesis of Emerging Infections Diseases in Humans,"Many viruses establish life-long infections in their natural host with few if any clinical manifestations. The relationship between virus and host is a dynamic process in which the virus has evolved the means to coexist by reducing its visibility, while the host immune system attempts to suppress and eliminate infection without damage to itself. Emerging infectious diseases pose a potential threat to public health such as human immunodeficiency virus (HIV), Severe Acute Respiratory Syndrome (SARS) virus and avian influenza. Our research focuses mainly on study of the host cellular immune responses to virus infections at the molecular, cellular and population levels. The aim is to gain a better understanding of the mechanisms of immunological damage (immunopathology) versus protection during the course of emerging pathogen infections in humans, and to apply this knowledge to the development of powerful therapies as well as effective vaccines.||Current work involves the following projects: 1) role of Nef gene in HIV-associated pathogenesis; 2) role of HGV (GBV-C) co-infection in HIV-1 pathogenesis; 3) functions of CD1 molecules and their role in virus infections; 4) immune responses to SARS coronavirus; 5) immune responses to influenza virus infection.",2021,2010,MRC Human Immunology Unit,2212207.94,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2005 +C17930,MR/P02551X/1,A one health approach to the investigation and control of MERS-CoV among camel and human populations in Jordan as a potential model for the region,"A stratified multi-stage cross-sectional survey will be conducted among Bedouin communities and their camels in the southern governorates of Jordan (Aqaba & Ma'an) during the period April 2017 to April 2018. These governorates have been selected due to their high number of camel owners, long porous border with Saudi Arabia to the south and already established RVC relationships. Camel owning households and and non-camel owning households will be randomly selected in a 4:1 ratio using local government data of registered livestock owners. Blood samples and oral and nasal swabs will be collected from all family members and a physical examination performed. A pre-tested, structured questionnaire to identify risk factors for MERS-CoV infection will also be administered at this time. Based on an expected prevalence of 4% MERS-CoV seroprevalence among camel owning households and a 0.5% expected seroprevalence among non-camel owners (a risk ratio of 8) a 1:4 ratio of camel herders to non-camel herders and an 80% power, with a 90% confidence interval and a design effect of 1.25 to account for clustering - sample size has been calculated as 946 individuals, with 757 camel herders and 189 non-camel herders. Nasal swabs will also be taken from those camels belonging to selected owners. The number of camels to be randomly sampled per herd has been calculated as 11, using an expected prevalence of 15% and a confidence level of 80% and a mean herd size of 12. In herds of less than 11 camels all camels will be tested. Human serum samples will be screened using anti-MERS coronavirus ELISA (IgG) with microneutralization assay performed as confirmatory test. Human nasal and oral swabs, and camel nasal swabs will be tested by PCR to identify MERS-CoV viral RNA. All samples will be shipped to the US and diagnostics performed at NIAD/NIH Virus Ecology Group, Rocky Mountains Laboratories, Montana. Laboratory and risk factor data will then be subject to multivariate statistical analysis.",2021,2019,Royal Veterinary College,647811.92,Animals | Human Populations,Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2017 +C17931,MR/V038230/1,Evidenced based mental health and wellbeing resources made by young people for young people in the COVID-19 context,"Young people have faced extensive disruption and challenge throughout the COVID-19 pandemic. There is good evidence to draw on to provide advice and support, but this is often not easily available to young people in accessible and engaging forms. As a joint proposal from the UKRI Emerging Minds and Triumph Networks, and supported by the wider Mental Health Networks, we are uniquely placed to draw on our cross-disciplinary, cross-sector, and lived experience networks to (i) draw together evidence on the mental health and wellbeing impacts of the pandemic on young people, (ii) identify priority areas where resources are needed, (iii) enable young people to develop resources that will be engaging and accessible to young people, and (iv) disseminate the outputs widely. Central aspects of our approach are (a) involvement of young people throughout, including creating opportunities for skills development and training to enable young people to be involved at all stages of designing and developing resources across a range of platforms, including (b) purposeful participation to address the needs of vulnerable groups who are likely to require tailored support and/or may face particular barriers to accessing support, and (c) collaboration with a wide range of partners who will both feed in insights and feed out outputs to ensure that the resources are disseminated widely through sources that young people trust. We are delighted to confirm that we have secured matched funding of £100,000 (Westminster Foundation) to maximise this opportunity to support young people at this unprecedented time.",2021,2021,University of Oxford,272153.23,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +C17932,MR/W006111/1,The UK Interstitial Lung Disease Long-COVID19 study (UKILD-Long COVID): understanding the burden of Interstitial Lung Disease in Long COVID.,"The COVID-19 pandemic has caused significant worldwide mortality and morbidity with >1 million people infected and >170,000 people hospitalised in the UK. Current estimates suggest 10-20% of non-hospitalised patients and 40-60% of hospitalised patients have long term symptoms, including breathlessness and fatigue, so-called ""Long COVID"". Emerging radiological and physiological features suggest Interstitial Lung diseases (ILD) including organising pneumonia and pulmonary fibrosis occur in up to 20% of hospitalised patients, although the precise burden and natural history of Long COVID related ILD (LCILD) is not clear. Given the large number of patients with persisting breathlessness there is an urgent need to identify and prevent the development LCILD. To improve outcomes for survivors of COVID-19 we will a) determine the prevalence of ILD following COVID-19, stratified by severity of infection and treatment, b) describe the phenotypes, c) determine the natural history and d) identify pathomechanisms and biomarkers of LCILD. Patients with documented COVID-19 will be recruited and the proportion of patients with symptoms, signs and investigations consistent with ILD between 3 and 6 months will be documented. In patients where ILD is suspected clinically this will be confirmed by Computerised Tomography (CT) scanning and patients will be stratified by pre-existing ILD, hospitalisation status, and therapy received. A subgroup of patients with proven LCILD will be re-consented for 12-month follow-up and deep phenotyping including 129Xenon-MRI and bronchoalveolar lavage. These data will define the burden of LCILD and inform the design of clinical trials to assess potential therapies to modulate progression of LCILD.",2021,2023,Imperial College London,2713174.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences",2021 +C17933,MR/W006243/1,TestEd: Developing and evaluating an affordable whole-system approach for early detection of viral infections in workplaces and communities,"Individuals with COVID-19 symptoms are eligible for diagnostic testing in the UK. However, due to cost and logistical constraints, pre and asymptomatic individuals are rarely tested or are screened with low-efficacy lateral flow devices, potentially allowing viral transmission. Although vaccination programmes provide grounds for optimism, there is no guarantee they will eliminate the virus if immunity is short lived, the virus mutates or there is low uptake. An efficient testing system is still needed for suppressing this and future pandemics. We have developed and validated two high-sensitivity, high-throughput approaches for detecting asymptomatic SARS-CoV-2 infection in saliva: (i) PCR-based hypercube pooling and (ii) sequence-based SwabSeq. We will directly compare the two approaches and test the hypothesis that they can be used at scale to detect asymptomatic SARS-CoV-2 infection early, reliably and affordably in up to half a million saliva samples from asymptomatic students and staff at Edinburgh University. We will survey participants to ensure our system is accessible and appropriate, and interview those who test positive to understand attitudes and behaviour regarding self-isolation. We will model the health economics of hypercube pooling and SwabSeq to compare their cost-efficiency and overall value with current testing methods. With an automated, user friendly system of participant registration, sample tracking, robotic processing and rapid result reporting, we aim to reduce the costs of regular screening to below 40p per test. This will enable testing of the whole University community twice a week, thereby minimising transmission from asymptomatic carriers. Our link to NHS Lothian Virology and its COVID service will allow positive cases to be re-tested and immediately entered into NHS public health systems. The study will provide a blueprint for large scale, regular testing to protect workplaces and communities from COVID-19 and future pandemics.",2021,2022,University of Edinburgh,2447872.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C17934,MR/W010011/1,Determining functional immunity after SARS-CoV-2 vaccination or natural infection in haemodialysis patients at high-risk of COVID-19,"Patients with comorbidities have a higher likelihood of death from SARS-CoV-2 infection. Amongst those worst affected are patients with end-stage kidney disease (ESKD), who are 45 times more likely to die than matched populations. Tragically, ESKD patients requiring haemodialysis (ESKDHD) cannot shield and face unavoidable risks of infection through the necessity to attend hospital for treatment. Despite their intrinsic susceptibility to COVID-19, ESKD patients can generate antiviral antibodies and thus may respond to vaccination. Nevertheless, it is unknown if after natural infection or vaccination: i) anti-viral serum and mucosal (salivary) antibodies are induced and maintained comparably to matched controls; ii) antibodies are functional and neutralise infection/promote opsonisation; iii) Whether host immune cells (neutrophils/macrophages) +/-antibody control virus infection.To answer these unknowns we will address the following hypothesis and objectives: Hypothesis ""Antibodies and immune cells from vaccinated or naturally-infected ESKD-HD patients and matched controls are equally effective at neutralizing SARS-CoV-2 infection"" Objectives:1. To identify the nature, magnitude and longevity of the systemic and mucosal B cell response to SARS-CoV-2 in naturally-infected or vaccinated ESKD-HD patients 2. To determine the functionality and neutralising capacity of serum and salivary antibodiesgenerated by ESKD-HD patients at different times post-vaccination/infection 3. To determine the capacity of different immune/non-immune cells from ESKD-HD patientsto resist infection in the presence or absence of antibodies From these studies, we will understand if virus-specific antibodies are friends or foes in these clinically extremely vulnerable patients and inform our approach to treatment, shielding and the benefits of vaccination.",2021,2022,University of Birmingham,601170.51,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C17935,MR/W015293/1,"Immune responses to SARS-CoV2 cause activation of platelets, resulting in thrombosis, which can be ameliorated by re-purposed drugs","Severe COVID-19 infection is associated with thrombosis in the lung, heart, kidneys and other organs, and is likely to contribute substantially to the high levels of mortality and morbidity in these patients. Whether abnormal platelet function accompanies disease progression is unknown. We will use deep-phenotyping approaches combined with established multi-parameter analysis to determine whether platelet function is altered in patients upon hospital admission, if this changes through disease progression, and whether levels of change correlate with disease severity. This will be incorporated an interventional study (MATIS) designed to test the benefits of repurposing drugs that target signalling proteins expected to diminish the inflammatory response to virus, which is proposed to lie behind severe disease pathology. These targets, the kinases Syk and Jak, also regulate platelet function. We will therefore also assess the impact of drug administration on platelet function, in comparison with standard of care, and establish whether potential benefits are associated with diminished platelet function. Preliminary data indicate that abnormally glycosylated antibodies produced early in COVID-19 infection enhance platelet function through stimulation of the platelet IgG receptor. We will therefore also determine whether immune-driven activation of platelets (thrombo-inflammation) is inhibited by the licenced Syk and Jak inhibitors.The outcomes from this study will establish whether abnormal platelet function lies behind life-threatening COVID pathology, and whether use of drugs that target both the platelet and immune responses to the virus offer promising therapeutic options. If successful, drug repurposing would offer the potential for rapid impact on patient outcomes.",2021,2022,University of Reading,499420.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2021 +C17936,MR/W015374/1,TB and COVID-19 coinfection: Investigating the clinical and biological interactions between Mycobacterium tuberculosis and SARS-CoV-2,"UKRI priority areas include understanding the interaction between SARS-CoV-2 and other pathogens. M.tb and SARS-CoV-2 have significant potential to interact and therefore impact on clinical outcomes.The two major knowledge gaps to be addressed by this project are: 1 The reciprocal biological impact of SARS-CoV-2 and M.tb on immunity to each other 2 How the pandemic has affected outcomes and the provision of TB services. Research to date has focussed on retrospective studies exploring relationships between TB and COVID-19 and suggest M.tb increases susceptibility to SARS-CoV-2 and disease severity. The control of LTBI requires the maintenance of effective T-cell responses. When these are perturbed (e.g. HIV infection, anti-TNF treatment), the risk of reactivation increases significantly. SARS-CoV- 2 infections may cause lymphopenia and the impact of this on M.tb-specific T-cell response is unknown, nor is it clear if these return to normal levels. One reason for the lack of understanding of the relationship between these pathogens is the limited availability of sufficiently-sized populations of M.tb-infected patients and the clinical infrastructure to assess them. The assembled team has the appropriate expertise to address these issues and the cohorts of patients within a single joined-up health region.",2021,2022,University of Birmingham,429001.63,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C17937,MR/W016729/1,"OpenSAFELY, ISARIC, PHOSP: tracking consequences of COVID-19 infection across UK primary and secondary care.","The prevalence and severity of health consequences for patients who have had COVID-19 are not currently known. There is also little data on which patients are most at risk of ongoing health and care needs. We must understand post-covid prognosis and risks to inform choices around prevention and treatment, design services, predict need, inform patients about their risks and prognosis, mitigate individuals' risks, and improve clinical outcomes. We will link data and combine expertise from three key projects to provide an unprecedented, comprehensive, longitudinal, patient-level view on COVID-19 patients in England: OpenSAFELY, running across patients' full primary and secondary care electronic health records (40% of patients in England, rising to 95% during the course of the project). ISARIC, with detailed data on >80,000 COVID-19 patients' in-hospital presentation and management. PHOSP, collecting bespoke symptom and laboratory data over 12 months on 10,000 hospitalised COVID-19 survivors. Using OpenSAFELY EHR data linked to ISARIC and PHOSP cohort data we will:- Assess risk of specific diagnoses, presentations, treatments, investigation findings, and symptoms that are elevated following COVID-19, in hospitalised and non-hospitalised patients. - Evaluate the impact of age, ethnicity, prior medical history, COVID-19 disease severity and in-hospital treatment on variation in recovery and complications. - Evaluate the extent to which PHOSP findings generalise to non-admitted COVID-19 patients. - Describe the impact of ""long COVID"" on health service utilisation to help predict service design and need.- Estimate excess morbidity associated with COVID-19- Develop tools to inform shielding policy based on long-term outcomes. - Share open code resources.",2021,2022,University of Oxford,826115.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Indirect health impacts",2021 +C17938,MR/W021242/1,Using data to improve public health: COVID-19 secondment,"The COVID-19 pandemic has placed considerable pressures on health systems. During the first COVID-19 wave in the UK, a large amount of NHS activity was postponed to free up capacity to treat patients with COVID-19. Some of this postponed activity was tackled in the summer when cases were lower, but subsequent waves have had similar impacts on healthcare. While there has been greater resilience in the NHS since the first COVID-19 wave, there has still been significant disruption that continues to affect the level of care delivered. It has been estimated that there were 4 million fewer elective treatment pathways in England in 2020 than compared to 2019. Cancer screening programmes, non-essential surgeries and diagnostic procedures were postponed or cancelled. Waiting lists have continued to get longer, resulting in delayed access to care for new treatment pathways. The impacts of healthcare disruption are unlikely to have been evenly experienced across society. The COVID-19 pandemic has amplified existing social and health inequalities, with groups from low socio-economic status and from marginalised backgrounds disproportionally affected in terms of their health and social outcomes. Early evidence suggests that disruption of elective treatment pathways has been greater in deprived areas. Narrowing health inequalities represents a key government priority, and therefore tackling any inequalities resulting from healthcare disruption will be key to ensure inequalities do not widen as a result of the pandemic. The fellowship will look to answer the following overarching research question: To what extent did healthcare disruption lead to negative health and wellbeing outcomes, and for whom? To answer this research question, the project will further answer the following ancillary research questions: 1. Who was affected by healthcare disruption during COVID-19 (including during different phases of the pandemic)? 2. Where was healthcare disruption greatest and did this contribute to geographical inequalities in health outcomes? 3. Were people more likely to have a delayed diagnosis of health conditions during COVID-19 (i.e., present at healthcare later than normal), for which conditions, and for whom? To answer our research questions, we will utilise two main types of data. First, linked longitudinal records will be used to assess the impacts of healthcare disruption. We will use the core UK cohort studies, with their additional COVID-19 waves that ask individuals about their experiences of health care disruption, to examine the impact on individuals. These data have been recently linked to health and care records, allowing analyses to investigate the nature of their disruption and any impacts on health. We will follow established methods deployed by the National Core Studies teams, with individual regression-based models fit on each independent cohort dataset and then a meta-analysis to combine insights collectively. Second, we will interrogate large administrative records of health care utilisation and mortality outcomes to examine the short- and longer-term population impacts of any disruption on health systems. We will explore general measures that may be influenced by any disruption (e.g., amenable mortality), as well as investigate specific pathways through which disruption may produce negative health outcomes (e.g., cancelled cancer screenings resulting in individuals presenting at later stages of cancers). Analyses will include descriptive statistics, GIS and data visualisation, interrupted time-series and regression-based analyses.",2021,2022,University of Liverpool,152806.21,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C17939,MR/W021277/1,Using data to improve public health: COVID-19 secondment,"During my secondment with the Centre for Longitudinal Studies (CLS), I will conduct research examining the impact of long covid on employment and income disruption, as well as how COVID-19 has disproportionally affected some populations compared to others, reflecting and perpetuating existing UK health inequalities. To conduct this research, I will analyse data from CLS's four national longitudinal birth cohort studies: the 1958 National Child Development Study, the 1970 British Cohort Study, Next Steps and the Millennium Cohort Study. During the pandemic, CLS have conducted an additional COVID-19 survey, administered to participants of these birth cohorts as well as participants in the National Survey of Health and Development. The aim of this COVID-19 survey is to understand the economic, social and health impacts of the COVID-19 crisis, the extent to which the pandemic is widening or narrowing inequalities, and the lifelong factors which shape vulnerability and resilience to its effects. My role, as part of the multi-institutional National Core Studies Longitudinal Health and Wellbeing initiative, is to utilise these cohort data to conduct studies focusing on i) COVID-19 severity and employment/income disruption and ii) Socioeconomic, demographic and geospatial determinants of COVID-19 infections. Both studies draw together data from multiple UK population-based longitudinal studies and electronic health records. Such research is crucial given that both the COVID-19 virus and non-pharmaceutical interventions implemented in response have led to a drastic change in the daily lives of the UK population. Understanding how individual's economic, social and health related outcomes evolve has considerable policy importance, since the pandemic is not only an infectious disease crisis but also an economic and social crisis.",2021,2022,King's College London,143406.29,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Economic impacts | Health service delivery,2021 +C17940,MR/W021315/1,Using data to improve public health: COVID-19 secondment,"The COVID-19 Longitudinal Health and Wellbeing National Core Study (LH&W NCS) commissioned Thriva to provide an end-to-end serological testing service, sending antibody test kits to roughly 47,000 cohort participants from 11 longitudinal population studies between March and May 2021. These cohort members span age groups of 18-75yrs, socioeconomic status and ethnicity and the overall return rate was 68%. This testing coupled with linkage to vaccination data and electronic health records now allows the meaningful analysis of associations between cohort/life course data and antibody response. It will also allow us to add a key layer to case definition in longitudinal population-based studies. In addition to Thriva data across cohorts, there are other cohort resources which can be used to enrich analyses further. For example, the Avon Longitudinal Study of Parents and Children (ALSPAC) is part of the UK Coronavirus Immunology Consortium (UKCiC) and has a programme of work focused on understanding the evolution of the immune response. The study has collected over 100 symptomatic known cases, and matched these to 100 symptomatic controls (with no COVID-19 diagnosis), and 100 symptom free controls. Participants provided biosamples, and questionnaire and additional functional data during in-person appointments and extended immunological data are now available which will allow comparison to Thriva based data. We will utilise available longitudinal population cohort data (as above) and four-nation linked health records via the Data & Connectivity NCS to investigate the biological and societal factors underlying the differential immunological response to COVID-19 infection or vaccination. Objective 1: Evaluate factors associating with low antibody levels post vaccination. Preliminary analysis in the TwinsUK cohort has shown tentative signs of association between low antibody levels after vaccination and sociodemographic and mental health factors. We will investigate using logistic regression models whether these findings are replicated in other cohorts and whether other associations with pre- and trans- pandemic health, sociodemographics and natural infection status can be found. Objective 2: Investigate factors associated with differences between symptomatic and asymptomatic cases following natural infection. The Thriva antibody data provides a way to define and examine asymptomatic cases of COVID-19 when matched with symptom data within the NCS cohorts. Deep immunophenotyping was performed on ALSPAC-UKCiC data and has shown that there is a difference in response measured in antibody and T cell values between symptomatic and asymptomatic cases following natural infection. The question arises about the underlying factors that cause symptomatic versus asymptomatic COVID-19 infection. However, this data set is relatively small and using Thriva antibody data across the 11 cohorts could provide a stronger signal for these underlying factors. Objective 3: Examine biological explanations for variation in infection and vaccine immune response. Preliminary analysis in the ALSPAC cohort has highlighted that people with a self-reported weakened immune system have a weaker antibody response following first vaccination. Using data from ALSPAC, we will look for associations between a weaker antibody response to vaccination and HLA haplotype, PRS genotypic risk, history of infection, trajectories of health, epigenetic and metabolomic variation and other immune variables. Where possible, we will investigate whether these findings are replicated in other cohorts and whether there are central biological explanations to variable response. Further exploratory research questions: How to maximise return from any future rounds of Thriva data collection? Can additional methods such as Mendelian Randomisation and machine learning algorithms be used in the analyses to give further useful insights?",2021,2022,University of Cambridge,157210.61,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2021 +C17941,MR/W021358/1,Using data to improve public health: COVID-19 secondment,"The fellowship will focus on making the best use of data from multiple sources to better understand the impact of COVID-19 on population health in the UK. The proposed research includes, 1. Identifying risk factors associated with Long COVID. o Use data from multiple sources, such as longitudinal cohort studies and/or electronic health records, to develop a prediction model to classify patients into groups with and without Long COVID. o Use unsupervised learning to further identify and define the subgroups of patients with Long COVID. 2. Evaluating vaccine effectiveness and safety using real-world (out of trial) data. o Evaluate and compare the effectiveness of different methods of vaccine offering: one dose, two doses of the same brand, and mixed brands of vaccine. o Evaluate vaccine safety, such as possible blood clots and heart inflammation, by using regression models for rare adverse events to better identify subgroups of patients at high risk. 3. Quantifying healthcare disruptions during different waves of the pandemic. o Analyse the data related to COVID-19 healthcare activity, to identify how the healthcare burdens change in different waves of the pandemic. o Investigate what factors are associated with healthcare burdens, what are the contributing factors in heterogeneity, and identify good practices in mitigating healthcare disruptions. 4. Assessing the effects of COVID-19 infection on other health outcomes. o Use electronic health records and/or multiple longitudinal cohort studies, to examine how COVID-19 infection impacts on other health outcomes. o Quantify how the effects of COVID-19 infection on health outcomes change with time. o Identify subgroups of the population who are more vulnerable to adverse health outcomes associated with COVID-19 infection. Well documented statistical code will be produced to allow for future updated analysis when new data become available, and for reproducible research.",2021,2022,University of Plymouth,158624.43,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures","Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences | Vaccine design and administration | Adverse events associated with immunization | Indirect health impacts",2021 +C17942,MR/W021390/1,Using data to improve public health: COVID-19 secondment,"This project will be delivered with colleagues from the Longitudinal Health and Wellbeing National Core Study (LHW NCS) and will focus on investigating the effect of COVID-19 on cancer and mental health of the population. It will use routine health data (electronic health records) from primary and secondary care. More specifically, the project will use platforms such as the NHS Digital Trusted Research Environment and OpenSAFELY, which link anonymised patient health records across different healthcare sectors, and make the data available for research in a way that is secure and transparent. The lead researcher on this project, Dr Lemanska from the University of Surrey, has already undertaken and published a study on the effect of the COVID-19 crisis on mental health. This research showed a dramatic drop in GP consultations for mental health during 2020, while the prescriptions system was more resilient and was not disrupted. The study discussed implications and recommendations for future pandemics in relation to switching to remote consultations and preventing backlogs in the NHS. This work led to a joint project with Public Health England (PHE) that compared the COVID-19-related disruption across healthcare systems including primary, out of hours and emergency care. The current research will contribute to the emerging picture regarding the wider healthcare implications of the COVID-19 crisis and in turn contribute to the national efforts in the fight against the pandemic. COVID-19 and lockdowns led to a shift in healthcare needs of patients. The pandemic has also affected the availability and readiness of NHS services to deliver healthcare and highlighted how difficult it can be to deliver healthcare under such challenging conditions. This project will build on Dr Lemanska's COVID-19 health disruption work. It will use linked electronic health records from different healthcare settings in the UK to investigate the impact of the COVID-19 pandemic and lockdowns on the delivery and outcomes of cancer care. Specifically, we will investigate how cancer screening and diagnostic testing was affected. For example, we plan to investigate prostate cancer and prostate-specific antigen blood tests which are used in primary and secondary care to detect cancer. In the area of mental health, we are interested in investigating the impact of COVID-19 on mental health. For example, we will look at how many people developed new mental health symptoms, new diagnoses, or needed new prescriptions for common mental health conditions such as depression, anxiety, alcohol and drug abuse, self-harm, sleep and eating disorders.",2021,2022,University of Surrey,159452.53,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C17943,MR/W021455/1,Using data to improve public health: COVID-19 secondment,"This project will develop computational methods to predict the severity and duration of COVID-19 using data on metabolic biomarkers from cohort studies and machine learning. Highly accurate predictions are crucial to identify the individuals that are most at risk of serious effects of COVID-19. The data to be used consists of sociodemographic information (age, sex, ethnicity, etc), information on health conditions before COVID-19, and metabolic markers from biofluids including blood, urine and faeces. Incorporating metabolomic data into the analysis is expected to significantly enhance our ability to predict the severity of COVID-19 compared to methods that focus on, e.g., sociodemographic data only. The project will study both the severity of COVID-19 and the duration of symptoms. The specific aims of the project are the following: Aim 1. To identify metabolic biomarkers associated with severe COVID-19 and long COVID. Aim 2. To train computer programs to predict the susceptibility of individuals to severe COVID-19 and long COVID. In practice, the aims will be separately addressed for the severity of COVID-19 and the duration of symptoms. The aim of the project, however, is to integrate the results for both characteristics and provide a general view on how metabolomics can help understand the manifestations of COVID-19. The severity of COVID-19 will be quantified in terms of whether or not patients show symptoms. For Aim 1, associations between the characteristics of individuals and the presence/absence of symptoms will be explored using statistical methods which will include graphical visualisation, hypothesis testing or logistic regression. Feature selection and dimensionality reduction strategies will be used to identify relevant features in terms of symptoms. For Aim 2, machine learning models will be trained to automatically classify individuals into symptomatic and asymptomatic classes. A variety of machine learning techniques will be implemented; partial least squares discriminant analysis, support vector machines or artificial neural networks are expected to be particularly suitable to deal with the high dimensionality and correlated character of metabolomic data. Several descriptions will be considered for the duration of symptoms which require different degrees of statistical power to be feasible. If the data gives enough statistical power, the most natural approach will be to consider the duration as a continuous random variable. In this case, Aim 1 will be fulfilled by using regression methods to assess the statistical significance of the different predictor variables for each individual. A range of machine learning methods will be explored to train a predictor for the duration of symptoms. Suitable candidates may include partial least squares regression, principal component regression or artificial neural networks. An alternative description of durations that will require less statistical power will consist in discretising the duration into several categories. For example, into short (≤10 days) and long (>10 days) duration to describe short and long COVID, respectively. In this case, Aims 1 and 2 can be achieved using methods similar to those described above for the analysis of the presence or absence of symptoms.",2021,2022,University of Aberdeen,160015.37,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Post acute and long term health consequences,2021 +C17944,MR/W02148X/1,Using data to improve public health: COVID-19 secondment,"Patients' willingness to seek timely medical treatment is instrumental in delivering adequate care. It is one of the National Health Service's (NHS) core missions to improve public health and well-being. Delayed treatment has been associated with higher overall healthcare costs and poor health outcomes. The COVID-19 (C19) pandemic had a profound impact on both the healthcare system as well as on patients. However, the impact of C19 on public willingness to seek timely treatment remains critically understudied. The secondment will be used to shed light on this aspect by analysing fully anonymised patient data within OpenSAFELY. Given the heavily redacted nature of the data, a combination of code lists from OpenCodelists need to be used to illustrate healthcare seeking behaviour. Specifically, healthcare seeking behaviour from patients who suffer from acute pain, as identified by all relevant CTV3 codes, are observed between the time the first national lockdown was introduced and after all restrictions had been lifted. It is hypothesized that medical treatment to alleviate pain was delayed during all national lockdown episodes due to public health interventions that aimed to protect the NHS from collapsing. Similarly, it is assumed that, on average, delayed medical treatment for acute pain patients continue to persist even after all protective public health measures had been lifted. In other words, it is hypothesized that some patients do not seek treatment for pain relief as fast as they would have prior to the pandemic. Mixed method time series modelling is used to estimate the hypothesised increase in delayed treatment. Competing explanations for delayed treatment are tested. Specifically, generalised linear models are used to derive odds ratios for competing explanations (e.g., C19 status). The aim is to identify relevant sociodemographic groups that would benefit from targeted campaigns to increase their tendency to seek timely treatment.",2021,2022,University of Sussex,131977.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C17945,NE/W002302/1,"Where coronaviruses hide, where novel strains are generated, and how they get to us: Predicting reservoirs, recombination, and geographical hotspots","Novel pathogenic coronaviruses, including SARS-CoV and SARS-CoV-2, arise by genetic recombining of two different coronavirus strains co-infecting an animal host. These viruses circulate in reservoir animal populations before spillover to humans. Understanding, monitoring, and mitigating both recombination and spillover requires identifying hosts that are susceptible to each coronavirus and hosts susceptible to multiple coronavirus strains (termed recombination hosts). However, the majority of coronavirus-host associations, and therefore reservoirs and recombination hosts, remain unidentified. This has led to an underappreciation of the potential scale of novel coronavirus generation and spillover. Here, we aim to predict all host species which act as SARS-CoV-2 reservoirs and recombination hosts (WP1), by expanding our tried-and-tested machine-learning framework to include avian hosts. This will enable monitoring of SARS-CoV-2 reservoirs during the pandemic, and hosts in which SARS-CoV-2 could recombine to generate novel pathogenic viruses. Geographical overlap of host species is a key predictor of between-species viral sharing. By constructing a species-level ecological contact network and integrating it with our framework we will further refine our predictions. This will enable us to identify geographical hotspots of coronaviruses recombination (WP2), and therefore enable specific spatially-targeted surveillance and mitigation efforts. Many coronavirus hosts interact with humans, either naturally by e.g. geographic/habitat overlap, or are used by humans as e.g. pets/food. Using geographical data from WP2 and host species utilisation data from open-access sources, we will (WP3) estimate the in situ likelihood of spillover from hosts identified in WP1. This will inform policy makers of species and hotspots for spillover mitigation efforts.",2021,2022,University of Liverpool,106758.6,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +C17946,S12883,Investigation of the coronavirus transcription mechanism,NA,2021,2003,University of Reading,204964.23,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2000 +C17966,,Transformations of STate cApitalism in a poSt coronavIruS world,"Responding to 'predatory' investors exploiting the pandemic Industrial and financial systems worldwide were impacted by lockdown measures imposed to contain spread of the coronavirus. Regional value chains, business competition and the world of work also changed dramatically. In this context, the EU-funded STASIS project will focus on the repositioning of European Member States with respect to investment from state enterprises, state-owned banks and state-sponsored investment funds, or what is widely referred to as state capitalist investment. There is concern that firms impacted by the pandemic might be targets of 'predatory' state-sponsored investors from beyond Europe. Grounded in geographical political economy, STASIS will use mixed methods of interviews with stakeholders and in-depth reviews of policy documents and case studies.",2021,2024,UPPSALA UNIVERSITET,233656.75,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Sweden,Sweden,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +C17968,,"'Stay home': emergency, (im)mobility, and the liberal subject","Understanding who the European liberal subject is during emergency situations As a result of the COVID-19 pandemic, exceptional measures to hinder the spread of this infectious disease have been and continue to be imposed in countries around the world. The EU-funded MOBILISE project aims at investigating how these emergency measures have impacted on concepts of citizenship, freedom and civic engagement, with a focus on resistance practice against forced immobility. To achieve this goal, the project will address important questions, such as what defines a good citizen during an emergency, and the characteristics that define a responsible citizen. The outcome of the project will contribute to a better understanding of the transformation that European citizens have undergone during the pandemic. Objective ""The MOBILISE project aims to critically investigate the COVID-19 emergency through the prism of (im)mobility and citizenship by scrutinising EU citizens' actions, reactions and inaction. By scrutinising acts of compliance, resistance and contentious politics in Europe, this project will critically investigate not so much emerging disciplining and policing practices but who the European liberal-subject-during-emergency is. By scrutinising the level of (non-)conformity as well as the reasons for it, it will be possible to map not only how common EU citizens have experienced, and are still experiencing, the crisis, but most importantly, what kinds of subjects/citizens have emerged out of it. Who is the 'citizen of emergency'? Or perhaps even better: what defines a good citizen during an emergency? Is it freedom? Is it democratic participation? Or is it responsibility? What does it mean to act as a responsible citizen? To what extent are the protests against and during the lockdown irresponsible acts? Which modalities of action make a citizen an irresponsible citizen? Is it the very act of contravening restrictions? Is it the non-compliance with health norms? In other words, should recent protests be investigated through the prism of citizenship and freedom, as traditionally done? Or should protests-during-emergencies be investigated through a different prism? These are some of the key questions that the MOBILISE project will investigate. By investigating citizen protests during and against governmental lockdowns, in Italy and in France, the MOBILISE project will uncover not only the modalities through which EU citizens are making their voices heard, but also the extent to which """"a new push for European democracy"" has emerged despite the many mobility restrictions.""",2021,2023,LUISS LIBERA UNIVERSITA INTERNAZIONALE DEGLI STUDI SOCIALI GUIDO CARLI,206059.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Italy,Italy,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions,2021 +C17969,,"Tacking informal employment in Asia: building post-COV19 solutions to precariousness through case-study based evidence on Bhutan, Laos, Maldives, Myanmar, Philippines, Thailand and Vietnam","Research and training on informal employment in Asia Informal employment and general labour insecurity are now widely recognised as major concerns worldwide. The International Labour Organization (ILO) estimates that approximately two billion people (61 % of the world's employed population) work in the informal economy, with numbers expected to rise in 2020 due to COVID-19. In spite of this, the capacity to address the problem of informal employment and vulnerability seems limited, especially in some regions of the world due, in large part, to the lack of regional specialists. The EU-funded LABOUR project has been designed to respond to this need and produce specialists on informal and precarious employment in Southeast Asia, where the phenomenon is particularly serious. Objective According to the last WESO report, there are over 1.4bn workers in vulnerable jobs worldwide, with numbers expected to rise in 2020 due to COVID-19. Several attempts have been made at both domestic and international levels to address these concerns. This includes efforts through the Sustainable Development Goals process, which includes a specific statistical indicator to measure informal employment (8.3.1) the formulation of SDG8 (decent work) and SDG9 (sustainable industrialization). Across countries and world regions, the degree to which SDGs have been used to address youth issues and inform national policies varies significantly. Indeed, in spite of the fact that the great majority of states have formally committed to addressing the SDGs, including those related to insecure employment, there is little evidence to indicate that developing regions currently have the capacity to systematically study the problems if informal employment and vulnerability in ways that facilitate the development and implementation of concrete viable solutions. This is due, in our view, to two major challenges. First, although a number of approaches that have been used inside the EU, there has been little, if any, attempt to adapt the existing framework elsewhere. Second, no systematic review of anti-precariousness policy has been attempted beyond the EU region. LABOUR is a research and training programme designed to address the above-mentioned shortfalls of research and development approaches with particular attention to a region where this is particularly worrying concern. Informal employment in Asia is estimated to account for 68.2% of the active population. By gathering a team of 14 participants that includes academic and non-academic partners working on labour insecurity, we aim not only at producing specialists on the topic and on the region but also at proposing concrete mitigation measures that can be taken into account by decision-makers and development organisations.",2020,2025,Tallinn University,1807424.64,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,South-East Asia | Western Pacific,,,,Estonia,Bhutan | Lao People's Democratic Republic | Maldives | Myanmar | Philippines | Thailand | Viet Nam,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +C17971,,Socially Distanced Solidarity: Far Right Recruitment and Enrolment During the COVID-19 Pandemic,"Elucidating the impact of COVID-19 on collective action and political protests Countries around the world have used different strategies to tackle the COVID-19 pandemic. For far-right organisations, the tactic of lockdown has impacted on their ability to recruit and enrol new members, which has repercussions for counter-radicalisation plans in the future. The EU-funded SODIS project will investigate how such organisations have altered their recruitment strategies during this time, their success as well as how the routes to joining have shifted. The project's work will contribute to research on social movements, collective action and radicalisation studies in addition to providing insights for those working in the fields of countering radicalisation and recruitment. The questions at the centre of the project Socially Distanced Solidarity: Far Right Recruitment and Enrolment During the COVID-19 Pandemic (SODIS) are how far right organisations have adapted recruitment strategies in time of crisis, namely the Covid-19 pandemic, how successful these strategies have been, and how pathways to joining have shifted as a result of the pandemic. The Covid-19 pandemic provides an unprecedented opportunity to examine changes in collective action and political protest, providing a natural experiment for policy intended to tackle radicalism. Due to lockdowns and partial lockdowns across the world, organisations have had to cancel protest activities and other events at the centre of many recruitment strategies; the ongoing threat of Covid-19 well into 2021 means that organisations must alter their strategies. The subsequent change, or lack-there-of, in recruitment numbers can have implications for counter-radicalisation strategies moving forward. SODIS relies on a modern research design focusing on various perspectives of organisation recruiters and new organisation members, and different national contexts, while taking advantage of this exceptional time in history. A quantitative online survey will lend to a better understanding of motives and attitudes of organisations members in four national contexts and to gain a better understanding of motives for joining organisations, qualitative interviews will be conducted in each country. SODIS will elucidate drivers of far right mobilisation and pathways to radicalisation, contributing to scholarship on social movements, collective action, and radicalisation studies. It will provide insight for practitioners working on countering radicalism and recruitment into such organisations, engaging with the conversation of how liberal and illiberal democracies deal with right-wing extremism .",2021,2023,UNIVERSITETET I OSLO,248381.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Norway,Norway,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C17973,,From human to planetary health: Global land-use impacts of the COVID-19 pandemic,"Protecting forests during a pandemic Protecting our natural forests is important to safeguarding human well-being and health. It can also prevent future pandemics. The case of the COVID-19 pandemic, resulting in a heightened level of urgency as regards planetary health, is taking a heavy toll on our forests. The EU-funded PlanetHealth project will explore the effects and mechanisms of the COVID-19 crisis on forest dynamics. For instance, changes in economic incentives are measured with global crop suitability maps, global crop price fluctuations and geocoded survey data. Project findings will shed light on the impact of COVID-19 on deforestation. The project's results will assist conservation strategies by investigating the dynamic relationship between health, global shocks and forest losses. Objective The COVID-19 pandemic is likely the most quickly and widely spreading global crisis of our times. Caused by a nature-borne disease, this crisis is introducing a new level of urgency to the global discussion on sustainability and planetary health as illness and death, economic uncertainty and governmental shut-downs reshape agricultural incentives at the global forest margins. PlanetHealth investigates the effects and mechanisms of the COVID-19 crisis on forest dynamics at the global and local level. It combines a global grid-based dataset (5-by-5 km) of high-frequency spatial data on forest outcomes (losses, fires, fragmentation) with spatialized ex-ante COVID-19 exposure measures. Changes in economic incentives across space are measured with global crop suitability maps, global crop price fluctuations, and geocoded survey data to analyze the labor market mechanisms at play. Their effects on natural habitats are expected to be spatially diverse, depending on bio-physical, economic, and political conditions. A channel analysis highlights the transmission effects along industry types (e.g. tourism, services) and household characteristics (e.g. education, female labor participation). PlanetHealth advances the environmental economics sciences by combining geographical and ecological methodologies with quasi-experimental econometric approaches. Relying on modern shift-share designs will allow for a causal quantification and spatialization of COVID-19 impacts on deforestation. Protecting the worlds' natural forests becomes increasingly valuable as a strategy to safeguard human well-being and health. PlanetHealth will inform such conservation strategies by investigating the dynamic relationship between health, global shocks, and forest losses. Understanding the heterogeneous pathways will generate valuable information for stakeholders who aim to mitigate the environmental effects of the current pandemic and to identify the strategies for tackling future crises.",2021,2024,GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS,307227.91,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Germany,Germany,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +C17974,,Interaction of SARS-CoV-2 virus with materials: a multi computational simulation study,"Objective This project proposes an atomistic modelling approach to the fundamental question of the interaction of enveloped viruses (in particular the SARS-CoV-2 virus responsible for the Covid-19 disease), with surfaces of materials. These interactions play a key role in indirect disease transmission through surfaces of materials contaminated with virus. This is particularly relevant in the case of the ongoing Covid-19 global pandemic; being the control of the disease transmission a priority everywhere. SARS-CoV-2 virus transmission mediated by contaminated surfaces has been identified in particular outbreaks, and the cleaning and disinfection of surfaces is known to be a major issue. Development of more efficient disinfestation strategies to break the transmission chain or the development of virucidal materials will be possible with a fundamental knowledge of the interaction of the virus with materials. The methodology to be employed will be atomistic simulations, based on the pre-existent deep understanding of the molecular structure of the virus. It should be noted that there is a substantial activity worldwide on atomistic simulations of the interactions between the virus components and possible antiviral drugs. However, the fundamental question of the interaction of the virus with materials remains largely unstudied. The main vision of this research project is to use state-of-the-art computational chemistry tools (MD simulation and QM/MM), to predict the interaction between the molecular elements of the SARS-CoV-2 virus envelope and surfaces of materials. We will consider various materials of interest and different thermodynamic conditions. The results of the present project not only will pave the way to identify the factors that influence the adhesion of SARS-CoV-2 virus to surfaces and to investigate the possible virucidal action of materials but also, will shed the lights to study the interaction of the other enveloped viruses like Influenza virus with materials.",2021,2023,AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS,203299.42,Viruses | Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control","Environmental stability of pathogen | Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2021 +C17975,,Hydrogel/Polymersome-based Subunit Vaccines in the Fight Against COVID-19,"Enlisting supramolecular hydrogels to fight coronavirus Most vaccines in use today were developed using techniques invented more than 100 years ago. The design of vaccines that have ease of distribution and reduced cost remains a major technological challenge. In view of the COVID-19 pandemic, there is growing pressure to develop new technologies to address severe infectious diseases. The EU-funded HYPOVACC project will develop a novel biocompatible, injectable and scalable vaccine technology based on supramolecular hydrogel-containing polymersomes to enable controlled local vaccine exposure for durable and broadly protective immune response against the coronavirus. The project research will cover new vaccine delivery technologies and recently developed immunological assays. Objective In light of current events, developing new technologies for the fight against severe infectious diseases, such as the COVID-19 pandemic caused by the SARS-CoV-2 virus, is a global health emergency. Despite the tremendous improvement of vaccine technologies, the design of potent, durable and safe vaccines displaying an ease of distribution and a reduced cost, remains a major technological challenge. This research project proposes to develop a novel biocompatible, injectable and scalable vaccine technology based on supramolecular hydrogels-containing polymersomes to enable a controlled local vaccine exposure for durable and broadly protective immune response against the SARS-CoV-2 infection. The platform will leverage supramolecular hydrogels as depot carriers for a sustained co-release of complex mixtures of immunomodulatory compounds comprising a typical vaccine and polymersomes to enhance the presentation of subunit antigens. Immunogenicity will be improved through potent immune stimulating-adjuvants mixtures, selected from a precise screening of vastly different molecules in terms of chemical nature and size, and a controlled multipresentation of antigens by fine-tuned antigen-grafted polymersomes. This highly innovative project will cover various disciplines ranging from chemistry, material science, to bioengineering, and will use new polymersomes and hydrogels constructs, vaccine technology and recently developed immunological assays. The proposal will be conducted in two internationally recognized leading teams in the field of drug delivery systems in Bordeaux University, France and Stanford University, USA. The international exposure and the outstanding scientific environment gained through the fellowship will be a key step for the independence and maturity of the researcher. She will acquire a unique multidisciplinary research profile which will be of significant interest for her future independent career in Europe.",2021,2024,UNIVERSITE DE BORDEAUX,311694.24,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Europe,,,,France,France,"Vaccines research, development and implementation",Vaccine design and administration,2021 +C18111,NIHR129783,"Air Filtration to reduce Respiratory Infections (including COVID-19) in care homes: the AFRI-c cluster randomised controlled trial with nested internal pilot, process and economic evaluations","Respiratory infections, such as COVID, coughs, colds and 'flu (influenza) are common in all age groups, but elderly people in care homes are more vulnerable because they are frail, have multiple health conditions and infections are easily spread within the shared space. As COVID has shown, respiratory infections in care home residents are also more serious, with many requiring hospital care and many not recovering. Less severe infections still require antibiotics, contributing to antibiotic resistance - itself considered a public health crisis. Respiratory infections are mainly spread when people breathe in or swallow airborne droplets containing germs. These are produced when others cough or sneeze. Care homes are required to follow the NHS 'Code of Practice on Infection, Prevention and Control (IPC)', but this focuses on preventing infections spread directly from contaminated hands or bodily fluids, and indirectly through germs settling on furniture or medical equipment. There are currently 220,000 people over 65 years living in UK care homes. This number is predicted to double by 2040, and as highlighted by the devastating effects of COVID in care homes, reducing the spread of infections in care homes is a research priority. Air filtration seems an obvious solution since high efficiency particulate air (HEPA) filters can quickly remove germs from the air. For years, they have been built into hospital operating theatres and transplant wards to prevent infections. But their use has not been tested in standard hospital wards or in care homes before. Now that HEPA filters are built into portable units available for domestic use, they can be placed in these locations with relative ease. We talked to residents, carers and staff at three care homes about the practicalities of putting air filters in communal areas and residents' rooms. Residents told us getting old and staying healthy is a priority, that AFRI-c is a 'no brainer' and that air filters would need to be installed carefully to minimise the risk of falls. Staff liked that air filters would add to existing IPC measures without disrupting the 'flow of care'. One air filter (made by PhilipsTM) was preferred because it was sturdier, had a night-time quiet mode, and a visible indicator of air cleanliness. Post-COVID, staff told us we should run the study remotely, with telephone and video support from the study team. They told us they feel confident this would be possible as they are now using Zoom and other online systems for many routine tasks. After care homes agree to place air filters in communal areas for one winter (September to April), up to 10 residents will be consented to have an air filter in their room, and to work with staff to report the number of infections they experience for the same period. We will divide the care homes into two groups at random (so they are similar), with one group receiving the air filters, and the other continuing with usual care. The study team will support all aspects of the study, without physically visiting the homes. Our experience suggests about 1 in 3 care homes and 1 in 3 residents will want to help. We will allow sufficient time to talk to relatives and friends of residents who do not have capacity (e.g. people with dementia) so they can take part. Our design also takes account of the 40% of residents expected to drop out of the study through moving away, illness or death.",2021,2024,"NHS Bristol, North Somerset and South Gloucestershire Clinical Commissioning Group",3160685.79,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C18112,NIHR135366,Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC),"Research question Does antiviral treatment in the community safely reduce hospitalisations/deaths in symptomatic patients with confirmed COVID-19? Background Many people with COVID continue to suffer serious acute illness, with hospitalisations remaining a significant burden on the NHS. Aims and Objectives PANORAMIC's primary objective is to assess effectiveness of novel antiviral treatment(s) in safely reducing all cause hospitalisation and/or death within 28 days from randomisation, in high-risk patients with a confirmed PCR positive SARS-CoV-2 test result in the community. The main secondary outcomes will be return to full-function, prevention of severe disease, reduction in symptoms, speed of recovery, including among clinically vulnerable groups. A Viral Load Sub-Study will investigate the impact of antivirals on viral load, time to virus clearance and an assessment of potential for development of resistance under drug selective pressure A Post-exposure Prophylaxis Sub-Study will determine how effective the antiviral is in preventing the transmission of SARS-CoV-2 when given to household contacts of index cases who have given consent. Methods PANORAMIC will have UK-wide reach. A master protocol will govern the platform trial with a Bayesian analytic approach. All enrolment (screening, informed consent, eligibility review and baseline data) and follow-up procedures (daily diary, data capture of hospitalisations and deaths) can be performed and captured online on the trial website or by telephone with a member of the trial team. Adults aged 18 or above who are clinically vulnerable and clinically extremely vulnerable, or aged 50 and above, with a positive SARS-COV-2 PCR test and symptoms of COVID-19 illness starting within the previous 5 days will be eligible. They will complete screening and informed consent online or by phone with a member of the trial team and be randomised to receive usual NHS care or an antiviral plus usual NHS care. Antivirals will be delivered directly to the participant using urgent courier. Participants will be asked daily whether they feel recovered by text, phone or email, for 28 days, and follow-up at 3 and 6 months for assessment of longer-term effects. Hospitalisation and deaths will be captured either patient report or by NHS Digital data extracts. Recovery will be patient reported. Safety will be closely monitored appropriate to the stage of development of each agent and availability existing data, with capacity for an intensive monitoring and sampling phase followed by potential graduation to a remote monitoring phase. Timelines for Delivery The University of Oxford University has demonstrated capacity for efficiently and effectively sponsoring national platform trials. Using our established broad approach, we plan to start on September 1st, 2021 with the first patient randomised within one or two months, with first findings out in 18 months. Impact and dissemination PANORAMIC will uniquely expand the evidence about the effectiveness of novel antivirals to benefit COVID patients in the NHS and worldwide. Results will be rapidly disseminated through pre-prints, publications and notification on the trial website, as well as direct to the MHRA, Antiviral Task Force, NICE, the WHO, and guideline developers world-wide.",2021,2023,University of Oxford,24746889.22,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Therapeutic trial design,2021 +C18113,NIHR134293,"Post-pandemic planning for maternity care for local, regional, and national maternity systems across the four nations","BACKGROUND One in 10 pregnant women contract COVID, but all are affected by pandemic-associated maternity service reconfiguration. AIMS To study the pandemic impact on maternal and offspring outcomes, focussing on virtual care, out-of-office monitoring, and the evolving vaccination strategy, to strengthen maternity services post-pandemic. OBJECTIVES 1) For all pregnancies, to study the impact on maternity care quality (effectiveness, safety, and acceptability), pregnancy outcomes, and costs within the context of maternity service configurations, particularly virtual consultations, out-of-office monitoring (eg, self-monitored BP), and COVID-19 vaccination (ie, provision, uptake, and adverse events): 2) Explore and describe the perceptions and experiences of pregnant and postpartum women during the pandemic, with a focus on those who: - identify with an ethnic minority group; - have medical or mental health co-morbidities; and/or - live with social complexity, including socioeconomic deprivation. 3) Across the four nations, engage with stakeholders to develop policy interventions for local, regional, and national health systems. METHODS Work Package (WP)1: QUANTITATIVE - describe, quantify, and explain We will use routinely-collected, linked maternity, mental health, and offspring data from the MRC-funded early-LIfe data cross-LInkage in Research platform ( 35,000 records currently) from a diverse area, South London. We will describe and quantify temporal trends in relevant health outcomes and costs, by service reconfiguration and inequalities (as above), using segmented and individual-level multivariate regression. We seek a coherent pattern of results to be interpreted in light of WP2 findings. WP2: SOCIAL SCIENCE - enrich understanding In-depth interviews with a maximum diversity sample of 90 pregnant/postpartum women, care-providers, and policy makers, with lived experience of maternity services during the pandemic. Interview schedules will explore what changed in care, its personal meaning, and confidence about care, analysed qualitatively (eg, thematic framework analysis). Questionnaires administered to maternity service users nationally ( 43,000) via the COVID Symptom Study (CSS) Biobank, recruiting participants from the King's College London-CSS/ZOE app, to understand vaccine uptake, hesitancy, and side effects. WP3: STAKEHOLDER ENGAGEMENT Regional listening events ('imaging our best future') in each UK nation will assess WP1 and WP2 findings; brainstorm, shortlist, and prioritise high-impact future actions; and understand relevant facilitators and barriers to implementation. National Policy Lab ('co-production for action') to explore listening event findings and produce an 'imagine our best future' report for dissemination. TIMELINES 01/Aug/2021 to 30/Jul/2023 DISSEMINATION Will be through established networks of local, regional, and national stakeholders, through engagement events across the four nations, virtual engagement (webinars, social media), academic publications, website, and report. IMPACT will be on: - Patients: improve care quality; - NHS maternity providers: evidence-inform service reconfiguration and vaccine role-out; - NHS Long Term Plan: address maternal and fetal/newborn death and morbidity and support digitally-enabled care implementation; - Society: innovation to commercialise and decrease costs.",2021,2023,King's College London,1363948.32,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Health service delivery,2021 +C18114,NIHR133779,PreHOspital Triage for potential stroke patients: lessONs from systems Implemented in response to COVID19 (PHOTONIC),"months 1-24]: We will use interviews, observations, and documentary analysis to analyse implementation of prehospital video triage, and how patients, carers, and healthcare professionals experience these services. We will use a case study design guided by a conceptual framework addressing implementation of digital innovations, informed by developing findings from a current service evaluation of the NC London and East Kent services. 2. Care delivery and outcomes",2021,2023,University College London,815868.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C18115,NIHR134607,Vaccine Response On/off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response?- A Randomised Controlled Trial,"Question: Does interrupting low-dose methotrexate treatment for two weeks after SARS-CoV-2 vaccine booster improve the immune response to it, and what are the underlying mechanisms? Background: Low-dose methotrexate has emerged as the first line systemic therapy for chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. However, its inhibitory effects on lymphocyte function causes suboptimal vaccine immunogenicity. A brief two-week treatment interruption after vaccination with the influenza vaccine protected 46% participants against all included strains compared to 22% participants with continued treatment. It is unknown if such a treatment interruption would improve immunity to vaccines against the SARS-CoV-2. This uncertainty resulted in conflicting advice from specialist societies, anxiety among patients, and may be addressed during the booster vaccinations in winter 2021. Aim: To examine the effects of a two-week interruption in low-dose methotrexate treatment (upto 25 mg/week) after SARS-CoV-2 vaccine booster on vaccine immunogenicity in people with inflammatory conditions. Study design: Prospective, parallel group, randomised controlled trial with internal feasibility assessment, and nested mechanistic study. Setting: Secondary care Population: Adults (age 18 years or more) with stable inflammatory disease, on low-dose weekly methotrexate, able to interrupt treatment for two weeks according to their consultant. Randomisation: 1:1 individual randomisation. Minimised by inflammatory conditions, age (40 year or less, 41-64 year, 65 year or more), SARS-CoV-2 vaccine received in current vaccination cycle (mRNA vs. other). Intervention: Advice to withhold methotrexate for two weeks post SARS-Cov-2 vaccine booster. Comparator: To continue with methotrexate as usual. Outcomes: Primary: Anti-spike receptor binding domain (RBD) antibody at week 4. Secondary: Anti-spike-RBD antibody at week 12; disease flare up, disease activity, treatment changes, quality of life at weeks 4 and 12. Mechanistic: Antibody neutralisation titres at weeks 4 and 12; effects of methotrexate adherence using validated bioassay on immunological outcomes. Research contact: 1] Pre-booster: consent, research assessments, blood collection. 2] Randomisation (phone): reconfirm eligibility, assess global disease activity. 3] Weeks 1, 2 (SMS): adherence to intervention, global disease activity (only week 2). 4] Weeks 4, 12: research assessment, blood collection. Analysis: Multi-level mixed effects models adjusted for randomisation factors and important prognostic factors using the as randomised population. Sample size: 560 participants (280 in each arm) will allow detection of an absolute difference of 25% anti-spike-RBD antibody, using 90%, 2-sided a=5% and 10% loss to follow up. 100 participants (50 in each arm) will participate in the mechanistic sub-study and provide additional blood samples for methotrexate adherence biomarker and neutralisation assay. Timeline: Set-up: months 1-3; Recruitment: months 4-16; Laboratory analysis: months 6 to 21; Data analysis: months 15-24. Write-up: months 21-24. Impact and dissemination: The findings will be disseminated to patients, the public, policy makers including the Joint Committee on Vaccinations and Immunisation, and Rheumatology and Dermatology societies where they will influence clinical practice.",2021,2023,The University of Nottingham,1259533.71,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Prognostic factors for disease severity | Clinical trials for disease management | Immunity,2021 +C18116,NIHR203306,"A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom","Although the risk to pregnant women following COVID-19 infection is generally low, there is a 2-3 fold increased risk of preterm birth for women with symptomatic COVID-19 and recent analysis of a large registry indicates that pregnant women are more likely to be admitted to an intensive care unit with COVID-19 than age-matched non-pregnant women. The current JCVI advice is that COVID-19 vaccines should be offered to pregnant women at the same time as the rest of the population, based on their age and clinical risk group. However, as pregnant women were specifically excluded from trials of COVID-19 vaccines, there are important and unanswered questions regarding the safety, immunogenicity and persistence of immunity in the vaccinated pregnant woman and her infant, as well as the optimal vaccination schedule to be used in this population. Using an ""adaptive"" platform design Preg-CoV will address these questions for current vaccines, as well as for new vaccines as they are approved. The primary objective of Preg-CoV is to determine whether the immune response at delivery (anti-S protein IgG concentrations) following immunisation with COVID-19 vaccines at ""long"" dosing intervals is superior to that following immunisation at ""short"" dosing intervals. Preg-CoV is designed as a single-blind, randomised, phase II multi-centre study. Eligible participants will be healthy pregnant women ≥18 years of age, between 13 and 34 weeks gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, no known increased risk for complications of pregnancy and no contraindication to the vaccines in the study. Women will be randomised to receive 2 doses of vaccines at either short (4-6 weeks) or long intervals (8-12 weeks). In the 28 to 34 week cohort, the 2nd dose will be provided after delivery, allowing the impact of one dose in pregnancy to be assessed. In the main (13-24 week) cohort, participants will receive a routine pertussis-containing vaccine at one of the visits; this will facilitate blinding of the schedule. A separate cohort will establish the response to a single dose in those who received one dose before pregnancy. All participants will have blood tests performed at baseline and 2-4 weeks post first and second doses, at delivery and at 12 months. Infants will have blood tests at day 0 (cord) and one further sample at either 6 or 12 weeks (via randomisation) to assess antibody kinetics. Breast milk samples will be obtained in a sub-group. The main immune outcomes will be the anti-Spike and anti-nucleocapsid immunoglobulins, neutralising antibodies, cellular immune responses, IgA and IgG against SARS-CoV-2 in breast milk (in a subgroup). Reactogenicity will be assessed through use of an electronic diary for 7 days post vaccination and a range of safety outcomes will be collected including pregnancy, including neonatal outcomes of special interest and infant development at 12 months. 200 participants will be recruited per vaccine included in the main cohort (100 in each arm). By collecting these data in a systematic and controlled manner we aim to inform evidence-based guidance for optimal vaccination of pregnant women.'",2021,2023,"St. George's, University of London",10140957.63,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation | Pathogen: natural history, transmission and diagnostics",Phase 2 clinical trial | Immunity,2021 +C18117,NIHR132748,"Background Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gut, most commonly presenting as Crohn's Disease (CD) and Ulcerative Colitis (UC). Over the last 12 months, our team in Cochrane Gut has worked with the UK British Gastroenterology Society (BSG) and Crohn's and colitis UK (CCUK) to examine key priority publications and then refine them into this programme to address only the most contemporaneous review gaps within the field. The COVID-19 pandemic has switched clinical work to remote telehealth options, as well as increasing demand for patient education to support self-management, but no synthesis of these techniques exists. With an increasing range of biologic options for CD, up to date synthesis to compare the full range of options is needed. However, biologics have also been a key concern during their pandemic, as there is a recognised infection risk with their use. Finally, many patients are interested in dietary supplements to change their symptoms and this represents a gap in the current Cochrane portfolio. Aims and objectives The scope of the programme will address these aims: - What is the efficacy and safety of patient education and remote management of IBD care? - What is the efficacy and safety of biologic and immunosuppressant therapies for Crohn's disease? - What is the efficacy and safety of supplements to normal diet for IBD? Methods This programme of 8 Cochrane reviews of varying size, scope and complexity will include three update reviews, five new titles including one network meta-analysis. A steering group will be established. The core team will consist of the Chief investigator, a full time experienced Cochrane reviewer, a senior researcher and a member of the CCUK patient information editorial board. All staff are in post and their time seconded, allowing timely project establishment. We will prioritise the reviews that will have direct impact during the COVID-19 pandemic. We will ensure the scope and outcome measures for every review are considered by the steering group. The Cochrane Gut group structure offers the support of our colleagues in the second Canadian base of the group for all editorial and review duties in an expedited fashion. Timelines for delivery In the first 3 months of the project the team will complete all protocols. Two of the new protocols are already in the final stage of peer review at time of this proposal submission. The core review work will be completed over 12 months, with the reviews grouped in three blocks by theme. Whist the grant is not supporting core CRG activity, the wider group allows significant contingency to ensure successful delivery of the programme. Anticipated impact and dissemination As well as the 8 published reviews, findings will be fed-back to the key stakeholder organisations to support prompt uptake. In particular, continuing our close working relationship established with CCUK and BSG, we will support their Knowledge & Evidence team and IBD committees respectively in updating relevant patient information and guidance for UK users. Additionally, keynote sessions at major scientific meetings are in place offer another route to dissemination, with most already shifting to virtual formats to continue during the pandemic. Finally, we have shared publication agreements with key journals in the field.","Background Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gut, most commonly presenting as Crohn's Disease (CD) and Ulcerative Colitis (UC). Over the last 12 months, our team in Cochrane Gut has worked with the UK British Gastroenterology Society (BSG) and Crohn's and colitis UK (CCUK) to examine key priority publications and then refine them into this programme to address only the most contemporaneous review gaps within the field. The COVID-19 pandemic has switched clinical work to remote telehealth options, as well as increasing demand for patient education to support self-management, but no synthesis of these techniques exists. With an increasing range of biologic options for CD, up to date synthesis to compare the full range of options is needed. However, biologics have also been a key concern during their pandemic, as there is a recognised infection risk with their use. Finally, many patients are interested in dietary supplements to change their symptoms and this represents a gap in the current Cochrane portfolio. Aims and objectives The scope of the programme will address these aims: - What is the efficacy and safety of patient education and remote management of IBD care? - What is the efficacy and safety of biologic and immunosuppressant therapies for Crohn's disease? - What is the efficacy and safety of supplements to normal diet for IBD? Methods This programme of 8 Cochrane reviews of varying size, scope and complexity will include three update reviews, five new titles including one network meta-analysis. A steering group will be established. The core team will consist of the Chief investigator, a full time experienced Cochrane reviewer, a senior researcher and a member of the CCUK patient information editorial board. All staff are in post and their time seconded, allowing timely project establishment. We will prioritise the reviews that will have direct impact during the COVID-19 pandemic. We will ensure the scope and outcome measures for every review are considered by the steering group. The Cochrane Gut group structure offers the support of our colleagues in the second Canadian base of the group for all editorial and review duties in an expedited fashion. Timelines for delivery In the first 3 months of the project the team will complete all protocols. Two of the new protocols are already in the final stage of peer review at time of this proposal submission. The core review work will be completed over 12 months, with the reviews grouped in three blocks by theme. Whist the grant is not supporting core CRG activity, the wider group allows significant contingency to ensure successful delivery of the programme. Anticipated impact and dissemination As well as the 8 published reviews, findings will be fed-back to the key stakeholder organisations to support prompt uptake. In particular, continuing our close working relationship established with CCUK and BSG, we will support their Knowledge & Evidence team and IBD committees respectively in updating relevant patient information and guidance for UK users. Additionally, keynote sessions at major scientific meetings are in place offer another route to dissemination, with most already shifting to virtual formats to continue during the pandemic. Finally, we have shared publication agreements with key journals in the field.",2021,2022,University of Central Lancashire,137583.85,Not applicable,Not applicable,Not Applicable,Not applicable,Individuals with multimorbidity,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C18118,NIHR135073,Understanding Mechanisms of Thrombosis and Thrombocytopenia in COVID-19 and with SARS-CoV-2 Vaccines,"Background Clusters of cases of cerebral venous sinus thrombosis (CVST) or thrombosis in other major veins, together with thrombocytopenia (thrombotic thrombocytopenia syndrome (TTS)) began to emerge following roll-out of SARS-CoV-2 vaccines. Although a mechanistic link is not yet proven, there is strong epidemiological evidence that TTS is a very rare adverse effect of SARS-CoV-2 vaccines, and in particular, adenoviral vectored vaccines. The incidence of vaccine-induced TTS is thought to range between 1 in 100,000 and 1 in 1,000,000 with a fatal outcome in up to 20% of cases. Research question We aim to investigate the mechanisms underlying TTS in response to SARS-CoV-2 vaccination with the ultimate goal of developing novel preventive and interventional strategies. Aims Evaluate SARS-CoV-2 vaccine safety using real world epidemiology data. Understand the prevalence of anti-platelet factor 4 (PF4) antibody positivity. Understand the relationship between the immune response initiated by COVID-19, vaccines and haemostatic dysfunction including the underlying genetic factors. Develop in vitro platelet models to understand mechanisms of vaccine associated adverse events, and identify potential therapeutic interventions. Timelines for delivery We expect important findings of relevance to public health to be delivered during the funding period (before August 2022). Our expected outcomes are: Epidemiological data that provides robust evidence of background rates of thrombocytopenia, thrombosis and TTS, and whether TTS is associated with any of the COVID-19 vaccines, including the magnitude of the effect. Robust laboratory data to show the background rates of anti-PF4 antibodies, and whether they are sensitive and specific indicators of TTS. Novel methods for preventing TTS including potential avenues to modify the vaccines to prevent TTS. Development of a clinical assay for TTS. Identification of improved treatment approaches for TTS to improve its prognosis. Anticipated impact and dissemination Our work will enable regulatory authorities to assess the relative risk of developing TTS in response to SAR-CoV-2 vaccine against that of becoming seriously ill with COVID-19. This understanding is important to ensure that populations worldwide receive maximum benefit from vaccination programmes. Understanding the mechanism for vaccine-induced TTS will inform development of second-generation COVID-19 vaccines and help to identify new therapies to reduce the case fatality rate associated with TTS. Our outputs will be of national and international importance. Initially, we will share new findings with the Vaccine Task Force (VTF), the Joint Committee on Vaccination and Immunisation, and other representatives of the Department of Health and Social Care (DHSC) . The DHSC will determine whether the findings are of ministerial interest. Press releases will be cleared with NIHR, DHSC and the VTF. Investigating the Genetic basis for TTS Genomics England, part of the consortium, is leading and funding complementary work investigating the genomics of thrombosis and thrombocytopenia related to COVID-19 and SARS-CoV-2 vaccines. The whole consortium will work together, and collaborate with other researchers worldwide, to develop a better understanding of TTS and maximise public health impact.",2021,2022,University of Liverpool,10140957.63,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +C18119,NIHR202685,COVID 19 - Palliative and End of life Care experiences of people of African and Caribbean decent (PEACE),"Background End-of-Life-Care (EOLC) improves health-related quality of life and life-expectancy (1), despite this one in four UK families miss out on crucial support particularly those from Ethnic Minorities groups (2-5). Research into EOLC for Ethnic Minorities is out-dated, out-with the UK, or from London, where Ethnic Minorities make up over 40% of the population (5-9). We know nothing of EOLC experiences of Ethnic Minorities in areas of the UK where they are more disparate, despite national research calls for such information (5). Key research policy priorities are to promote equity in EOLC, specifically to rectify ""poor outcomes amongst Black, Asian and minority ethnic (BAME) populations"" (8-12). BAME groups are heterogeneous. Older Black people are a crucial tracer population for achieving patient-preferred outcomes, and they experience some of the highest levels of material disadvantage (5,10-12). During the COVID-19 pandemic, deaths amongst Black populations have been twice as high as in White populations of similar socioeconomic status (13). Despite this Black people are still less likely to access end-of-life services (10,14-17), which play a crucial role in improving care (18). It is unclear why this is and how service changes have exacerbated this. Aims and objectives To identify family priorities for EOLC development, to meet the needs of Black people during and after the COVID-19 pandemic. We will explore family and patient (by proxy) views on; experiences of EOLC (positive/negative), barriers to EOLC and how EOLC could better meet Black people s needs. Methods We will conduct a qualitative study using in-depth semi-structured interviews. Bereaved relatives of decedents (>50 years) who identified as being Black African, Black Caribbean or Black other (13) and who died during the COVID-19 pandemic will be recruited/purposively sampled through community groups, social media and targeted online advertising (23). The sample will be balanced by relationship, gender-identity, age and decedent s illness (COVID-19/cancer/non-cancer). Previous experience suggests no more than 60 interviews will be required to ensure data sufficiency. Interviews will be conducted following COVID-19 guidelines. The topic guide, developed with PPI partners and drawing on VOICES survey domains (19), will allow participants to share their experiences. Prompts will elicit information about needs (met/unmet), experiences/views, support structures and barriers to care. We will use a modified theoretical framework of access and critical race theory which consider service availability, accommodation, affordability, acceptability and awareness (20-23). Policy engagement, dissemination and impact Our research will support policymakers to accommodate recent changes in service, whilst addressing structural, cultural and behavioural challenges to equitable EOLC. The team will undertake targeted dissemination of emerging findings, including 10-minute COVID-19 webinars and existing monthly Department of Health and Social Care/Policy Research Unit meetings from March 2021 until November 2021. We will also present findings to the National Clinical Director for End-of-Life and the National End-of-Life Care Intelligence Network. We will deliver three main outputs: A formal report and briefing of findings, following a 1/3/25 page format, for policy makers (November 2021), an article in peer-reviewed journal (December 2021); and public-facing report developed for bereaved relatives/carers (November 2021).",2021,2022,Newcastle University,140553.37,Human Populations,Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Research to inform ethical issues | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Research to inform ethical issues in Clinical and Health System Decision-Making | Community engagement",2021 +C18120,,"STIMULATE-ICP (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)","Developed with the help of patient organisations, this project will test the efficacy of existing drugs to treat long COVID, and measure the different effects of three months' treatment on patients with regards to their symptoms, mental health and other outcomes such as returning to work. It will also assess the use of MRI scans to help diagnose potential organ damage in those recovering from the coronavirus, as well as enhanced rehabilitation - the provision of joined-up specialist care centred around an app for patients allowing them to track their symptoms.",2021,-99,University College London Hospitals NHS Trust,9357480,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Pre-clinical studies", +C18121,,"This study focuses on identifying and promoting the most effective care for long COVID patients, ranging from accurate assessments in specialist clinics to the best advice and treatment in surgeries, as well as home monitoring methods that can show flare-ups of symptoms. Drawing from the experiences of current long COVID patients and NHS professionals, the research aims to establish a gold standard of care that can be shared across England and the rest of the UK. Analysis will be conducted in 10 long COVID clinics, at home and in doctors' surgeries, and the study will track referrals and evaluate different services through patient interviews to make sure they are efficient, accessible and cost-effective. Specialists in healthcare inequality will also ensure that views are sought and recorded from people who are not visiting clinics.","This study focuses on identifying and promoting the most effective care for long COVID patients, ranging from accurate assessments in specialist clinics to the best advice and treatment in surgeries, as well as home monitoring methods that can show flare-ups of symptoms. Drawing from the experiences of current long COVID patients and NHS professionals, the research aims to establish a gold standard of care that can be shared across England and the rest of the UK. Analysis will be conducted in 10 long COVID clinics, at home and in doctors' surgeries, and the study will track referrals and evaluate different services through patient interviews to make sure they are efficient, accessible and cost-effective. Specialists in healthcare inequality will also ensure that views are sought and recorded from people who are not visiting clinics.",2021,-99,University of Leeds,4678740,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health service delivery", +C18122,,EXPLAIN (Hyperpolarised xenon magnetic resonance pulmonary imaging in patients with Long-COVID),"The EXPLAIN project will seek to diagnose ongoing breathlessness in coronavirus patients who were not admitted to hospital, using MRI scans to trace inhaled xenon gas moving into and out of the lungs. A 15-minute scan using low levels of the gas will display lung function and - if abnormalities are found - comparisons of data across different groups of participants recruited from Oxford and Sheffield can help assess their severity and whether they improve over time. Some EXPLAIN patients will also have a separate scan to see if heart damage can be identified. If the MRI scans separate patients with and without lung disease, further CT scans can be analysed, using artificial intelligence and blood samples to identify associated conditions and inform the development of treatments.",2021,-99,University of Oxford,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences, +C18123,,CICERO (Cognitive Impairment in long COVID: PhEnotyping and RehabilitatiOn),"Up to three quarters of people who experience long-term symptoms after COVID-19 report problems with memory, attention or other cognitive functions - symptoms known collectively as 'brain fog'. This project will first determine which elements of brain function are most affected in people with long COVID. The relationship between brain function and other symptoms of long COVID, such as fatigue and anxiety, will be explored, and MRI scanning will be used to identify the affected brain networks. The researchers will then develop and test a new rehabilitation strategy to help people recover from the cognitive aspects of long COVID and return to normal life and working ability. This will support production of a freely available COVID-19 Cognitive Recovery Guide on how best to offer the new rehabilitation approach depending on the patient's symptoms.",2021,-99,University College London,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences", +C18124,,LISTEN (Long COVID Personalised Self-managemenT support - co-design and EvaluatioN),"In recognition that each person with long COVID can experience markedly different symptoms, the LISTEN project will work in partnership with patients to design and evaluate a package of self-management support that can be tailored to individual needs. The researchers will first work with people living with or recovered from long COVID, plus a social enterprise with expertise in reaching seldom heard populations, to design the package and associated patient and training resources. The team will then test the self-management package alongside up to six one-to-one virtual coaching sessions from trained rehabilitation practitioners, to test whether the treatment improves how people with long COVID feel and how they cope with everyday activities. The researchers will also evaluate how the package could be implemented more widely, with the aim that self-management for people with long COVID can be delivered at scale.",2021,-99,Kingston University,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health service delivery", +C18125,,ReDIRECT: Remote Diet Intervention to Reduce long Covid symptoms Trial,,2021,-99,University of Glasgow,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management", +C18126,,The immunologic and virologic determinants of long COVID,,2021,-99,Cardiff University,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity, +C18127,,Quality-of-life in patients with long COVID: harnessing the scale of big data to quantify the health and economic costs,,2021,-99,London School of Hygiene & Tropical Medicine,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts, +C18128,,Percutaneous Auricular Nerve Stimulation for Treating Post-COVID Fatigue (PAuSing-Post-COVID Fatigue),,2021,-99,Newcastle University,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences", +C18129,,Immune analysis of long COVID to inform rational choices in diagnostic testing and therapeutics,,2021,-99,Imperial College,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences, +C18130,,Understanding and using family experiences of managing long COVID to support self care and timely access to services,,2021,-99,University of Oxford,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health service delivery", +C18131,,Development of a robust T cell assay to retrospectively diagnose SARS-CoV-2 infection and assays as diagnostic and monitoring tools in long COVID patients,,2021,-99,University of Cambridge,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Post acute and long term health consequences, +C18132,,Impact of COVID-19 vaccination on preventing long COVID: a population-based cohort study using linked NHS data,,2021,-99,University of Oxford,2476980,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Clinical characterisation and management | Vaccines research, development and implementation",Post acute and long term health consequences, +C18133,,Long COVID Core Outcome Set (LC-COS) project,,2021,-99,King?s College London,192129.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Post acute and long term health consequences, +C18160,,Does zinc crosslinking in ACE2 control COVID-19 spike binding?,,2020,-99,N/A,2476980,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,Americas,,,,,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies", +C18166,,Investigation of SARS-CoV-2-bacterial co-infection dynamics to develop improved treatment options during pandemics,,2020,-99,Schulich School of Medicine & Dentistry,2476980,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies, +C18952,01KX2026,Experimental SARS-CoV-2 vaccine,,2021,2022,Ludwig-Maximilians-Universität München,2857703.03,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C18953,01KX2027,Experimental SARS-CoV-2 vaccine,,2021,2022,Philipps-Universität Marburg,79776.9,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C18954,01KX2040,Capacity mapping of clinical trial sites for COVID-19 vaccine studies in Europe,EUVAP is a platform for experienced clinical trial sites interested in conducting COVID-19 vaccine studies.,2021,2024,Universität zu Köln / Deutsches Zentrum für Infektionsforschung (DZIF),1902316.47,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2020 +C18955,not applicable,Medicines for COVID-19,,2021,-99,Drugs for Neglected Diseases Initiative,17860500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C18956,not applicable,Development of diagnostics for COVID-19,,2021,-99,Foundation for Innovative New Diagnostics,71442000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C18957,01EP2104A,Physical activity & Long-COVID-Syndrome,"The proposed research project aims to explore an individualized endurance-oriented training intervention program for patients with persistent symptoms after an infection with SARS-CoV-2 (Long-COVID-Syndrome) in terms of its basic safety, feasibility and general effectiveness, as well as to derive concrete recommendations for a training intervention programm. The project will be carried out within a period of 12 months in the sense of a pilot project. The overall goal of the research project is to develop recommendations for specific exercise programs capable of improving the overall health status of Long-COVID patients through physical activity. Necessary structures for recruitment and ongoing randomization of study participants will be established in order to include a total of 60 probands in the study showing Long-COVID symptoms, especially cardiological and respiratory fitness parameters, but also the development of general Long-COVID-associated symptoms (e.g., headache, fatigue, exhaustion) (n=30 intervention arm, n=30 control arm). Subjects will be recruited from the existing study population from the COVID-19 health study taking place at IMIBE. These subjects will undergo comprehensive sports medicine examinations in monitored entry examinations and with a repeated examination 3 months after inclusion in the study. The study data will be controlled, maintained and managed by data managers to ensure a high quality of data for subsequent scientific data analyses, which will be published in peer-reviewed journals. The study results may serve as the basis for future studies to confirm and quantify the effectiveness of specific training programs. Study results will also indicate whether reduced physical activity, as a result of acute SARS-CoV-2 infection, is part of the underlying causes of persistent COVID-19- symptom.",2021,2022,Universität Duisburg-Essen,329628.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C18958,01EP2104B,Physical activity & Long-COVID-Syndrome,"The proposed research project aims to explore an individualized endurance-oriented training program for patients with persistent symptoms after an infection with SARS-CoV-2 (Long-COVID-Syndrome) in terms of its basic safety, feasibility, and general effectiveness, as well as to derive concrete recommendations for a training intervention programm. The project will be carried out within a period of 12 months in the sense of a pilot project. The overall goal of the research project is to develop recommendations for specif-ic exercise programs capable of improving the overall health status of Long-COVID patients through physical activity. The aim of the present sub-project is to design a suitable, primarily endurance-oriented training program, individualized according to performance, age, sociological framework and motivation, which is then instructed and monitored during the project phase.",2021,2022,IST - Hochschule für Management GmbH,36893.01,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Europe,,,,Germany,Germany,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C19389,224924/Z/22/Z,Exploring the Genetic Architecture of Clinical Clusters of COVID-19 Patients.,"It has been observed that critically ill COVID-19 patients exhibit a wide range of clinical phenotypes which also affect the patients' response to treatment. The group I am joining has shown that 25 genes are significantly associated with individual risk of developing serious illness following infection with SARS-CoV-2. Understanding the genetic background of COVID-19 patients may improve current treatment of the disease by identifying therapeutic targets. I aim to divide a set of 8788 critically ill COVID-19 patients into different groups based on clinical information available at the time of hospitalization. By comparing the effect sizes for known genetic associations across clinical subgroups, I aim to identify genetic markers for differential therapeutic effect. My project will deepen understanding of the genetic mechanisms underlying critical illness in COVID-19 and may discover genetic predictions of differential therapeutic effect that could, in future, direct the design of stratified clinical trials.",2021,2024,University of Edinburgh,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2021 +C19390,224918/Z/21/Z,"Coronaviridae's 'Utility Belt': Identification, Characterization and Evolutionary Analysis of the Accessory Proteome of SARS-CoV-2 and other Coronaviruses","Despite the great efforts of international vaccination campaigns, the COVID-19 pandemic remains a major global health threat, as no antiviral drugs are available for severe COVID-19 patients, and the emergence of mutant viral strains risks to nullify vaccinations' efforts. SARS-CoV-2's genome has been found to encode for several strain-specific, non-essential accessory proteins with diverse functions. Some of these are known to be expressed from overlapping sequences within structural genes (e.g. 9b/9c within the Nucleocapsid (N) gene), but other overlapping sequences' potential for protein production remain unascertained. To identify new targets for drug development and help assess the threat variants pose to public health, it is crucial to identify these protein-coding sequences, study their products' functions and understand their origins. Our goals are to: Identify additional potential accessory genes encoded within SARS-CoV-2 N gene through in vitro translations and cell viability assays. Assess their role in in vitro infection models through generation of mutant SARS-CoV-2 strains. Dissect the dynamics of accessory gene birth/death in SARS-CoV-2 and related coronaviruses through phylogenetic analyses and dN/dS calculations. Test the hypothesis that coronaviruses adapt to changing host environments by acquiring/losing accessory genes by expressing a functional library of coronaviruses' accessory genes in multiple cell systems.",2021,2024,University of Edinburgh,0,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C19391,224917/Z/21/Z,Investigating Human Host Factors Involved in Coronavirus Infection in the Search for Antivirals,"SARS-CoV-2 is the virus that causes COVID-19 in humans and has resulted in a global pandemic since March 2020. Viruses are small pathogens that need to find, bind and enter host cells to replicate and assemble new virus particles that are then released to infect neighbouring cells or other hosts. This project aims to find parts of the human cell (known as host factors) that are involved in SARS-CoV-2 infection. I will continue research from a large experiment which will identify host factors that either help or hinder the virus. We can then use drugs to either inhibit that which helps the virus (pro-viral factors), or promote that which fights the virus (anti-viral factors) to develop antiviral therapies for the treatment of COVID-19. Drugs with potential antiviral activity in cell models may then be moved to preclinical mouse models to test if they work against SARS-CoV-2 infection and are safe. I will also assess if any drug targets are translatable to other coronavirus infections. Finding drugs that act against a broad range of coronaviruses may be important in the event of a new, infectious coronavirus outbreak in future.",2021,2024,University of Edinburgh,0,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C19392,224897/Z/21/Z,Network analysis of multimodal COVID-19 patient datasets,"Over recent years there has been an enormous number of developments in the ways we obtain molecular information from patients with disease. This has resulted in the ability to generate multiple measurements per patient for large cohorts, including levels of various proteins in their blood stream, gene activity across multiple different cell types at the resolution of single cell as well as precise methods of counting the numbers of different cells present in the system of interest. At the same time, there is an acute need to integrate this information and enable using all the data at once and not one at a time. Multilayer networks which at each layer summarize information available from a single experiment and then connect these layers allow us to integrate molecular information across various molecular measurements. We aim to develop statistically robust network methods and apply them to a dataset of more than 100 hospitalized COVID-19 patients of different severities. We also aim to compare them with sepsis, hospitalized flu patients and COVID-19 non-hospitalized patients and healthy volunteers to discover better ways to stratify patients and understand the underlying biological mechanisms driving their disease.",2021,2024,University of Oxford,0,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2021 +C19393,224847/Z/21/Z,INGSA learning & outreach,"This proposal repurposes funding that Wellcome had intended for use to support LMIC delegate travel to the INGSA biennial conference. It would now enable acceleration of our Online Outreach and Training Strategy. Our current funding envelope pre-dates the pandemic, and did not anticipated the extent of online delivery now required. We have tried hard to transform programming with existing resources, but gaps remain. Will now focus on delivery of accessible, inclusive and interactive capacity-building online. We have content that can be turned into pedagogically-robust modules and made available via a reputable learning platform. Deliverables include: ""INGSA Shorts"" series of 2-3 minute videos which condense learning/wisdom from the 2021 conference (estimated cost: $12,000 NZD) Minimum three MOOC-style courses, framed around the conference's themes: Science Advice in Crisis (i.e. lessons learned from the pandemic); Science advice for complex/long-term issues (i.e. foresight/resilience; Evidence/democracy. Content drawn from 2021 conference and other Wellcome/IDRC funded programming including past LMIC workshops, the Covid-19 comparisons, Knowledge Associates projects. This approach leverages the full complement of INGSA programming (estimated cost: $28,000 NZD) We will work with new INGSA Board and LMIC partners to co-design, contextualise and field-test material, ensuring that content and format is robust and appropriate to context.",2021,2023,University of Auckland,27292,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Western Pacific,Western Pacific,,,,New Zealand,New Zealand,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening,2022 +C19394,224846/Z/21/Z,Providing the scientific evidence and tools for reaching 2021-2030 NTD Roadmap goal of eliminating schistosomiasis as a public health problem in Africa,"The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as those which are neglected by research and funding, and disproportionately infect poor and marginalised communities. One such NTD is schistosomiasis, a waterborne parasitic disease which infects over 250 million people worldwide, and is second only to malaria in terms of socioeconomic burden. In the new NTD roadmap 2020-2030, the WHO aims to eliminate schistosomiasis as a public health problem by 2030. Preventive chemotherapy has been a pillar of intervention strategy for many years in endemic countries of Africa, but some regions do not respond as expected, with persistent high prevalence of schistosomiasis. In this PHD I aim to investigate factors which could be maintaining these persistent hotspots, and therefore hindering the goal of elimination. I will investigate whether using preventive chemotherapy at a defined time in the transmission pattern of S.haematobium would reduce prevalence and reinfection. I will also carry out a survey of attitudes and practices involving WASH in Zimbabwe with a focus on COVID-19 and its effects on endemic schistosomiasis. Finally, I will explore genetic differences in parasite populations, post treatment in persistent and non-persistent regions, allowing an investigation into parasite susceptibility to treatment.",2021,2024,University of Edinburgh,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19395,224770/Z/21/Z,Framing inequalities through causal stories: a cross-case comparison and critical reflection,"Despite being a central focus in research, policy, and practice in recent years, health inequalities have widened and are being further exacerbated by the Covid-19 pandemic. The reasons are multiple and complex, but there is increasing concern that the framing of health inequalities may be contributing to implementation challenges. This is important because while the health sector is not alone in grappling with socially-driven inequalities in outcomes, there is a persistent desire to embed a 'health inequalities' perspective across all sectors and policies. The aim of this research is to employ theoretical and methodological tools from framing analysis to explore, compare, and critically reflect upon different ways in which inequalities in outcomes are framed across multiple sectors beyond health. These sectors include early years education, youth justice, and housing, and, for each, data will be collected through documentary analysis of academic literature and policy reports; semi-structured interviews with actors working to reduce inequalities; and group 'framing reflection' exercises. The research will produce novel comparative analyses, and interdisciplinary reflections, on contrasting ways of framing inequalities. These findings will illuminate the potential for more cross-sectoral accounts of inequalities that would lead to greater collective understanding and action on the cross-cutting underlying causes.",2022,2025,Lancaster University,252106.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C19396,224734/Z/21/Z,"The Rise of Mask-Wearing in Republican China: Colonialism, Epidemics, and Issues of Governance (1912-1949)","During the current COVID-19 pandemic, the Chinese government celebrated face masks as symbols of modernity and national pride. This project hypothesizes that face mask's authoritative position in China's epidemic control today is rooted in Chinese history, specifically the semi-colonial period, when foreign powers and internal political forces were competing for control of China. This project argues that this narrative, of mask-wearing as an integral part of Chinese culture and politics today, is a modern myth. To unpack this myth, this study explores the parallel policies of the British and Japanese Empires, and China's Nationalist and Communist Parties, in promoting mask-wearing as a form of epidemic control. This project will produce a comprehensive account of the social history of medicine on mask-wearing in the semi-colonial Republican period (1912-1949) in which it asks, 'How did British and Japanese colonialism, and China's domestic politics, contribute to masks' authoritative position in semi-colonial China?' To answer this central question, the project is structured chronologically around four themes: 1) Masks, race, and epidemics in the 1910s Shanghai International Settlement; 2) The national recommendation of mask-wearing in the 1929; 3) Japanese military promotion of masks in Manchuria (1930s-1940s); and 4) Chinese Communists' wartime mask-wearing campaigns.",2022,2026,University of Manchester,327516.6,Other,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2023 +C19397,224712/Z/21/Z,'Ripping up the rulebook': Experiments in post-pandemic substance use treatment,"If we take death as the ultimate harm, the UK has never been a more harmful place for people who use substances. Death rates from both drug- and alcohol-specific reasons are at their highest ever level. Moreover, some areas are experiencing their worst HIV outbreaks among injecting drug users in 30 years, and alcohol-related liver disease is rising steeply. As Covid-19 works to 'expose and amplify' existing inequalities, the fear is that these deaths/harms will increase further. However, Covid-regulations have also brought drastic changes to the sector, including long-sought flexibilities in treatment options and regimes. Prominent practitioners refer to these as 'ripping up the rulebook' and a 'natural experiment' with 'potential for a lot of learning'. This project studies these experimental practices and what they open-up for improving treatment attractiveness and responsiveness. It maps experiments in service provision through a UK-wide survey and carries out ethnographic inquiry to establish how these practices re-work treatment and the role of service users' own experimentations in these processes. Extending this experimentality through its methodology, the project brings together key stakeholders in a theatre-informed workshop to quite literally 'rip up the rulebook' (clinical/policy guidelines) to provoke further thinking and action on treatment possibilities.",2022,2027,"Goldsmiths, University of London",437703.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2022 +C19398,224686/Z/21/Z,Improving leadership in primary science,"The Primary Science Quality Mark, based at the University of Hertfordshire is seeking a discretionary grant of £149,775.00 from Wellcome to enable it to increase its ability over the next two years to improve leadership in primary science in UK schools most affected by the Covid-19 pandemic. This will address gaps in provision and increase children's access to exciting, inspiring and relevant science education that leaves them well-prepared to progress further in science, and well-informed about science in their everyday lives.",2021,2023,University of Hertfordshire,204382.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",,2021 +C19399,224677/Z/21/Z,The Innate Immune Barriers that Constrain the Emergence of Coronaviruses into the Human Population,"The COVID-19 pandemic has shown us the consequences of coronaviruses jumping from an animal into humans. Coronaviruses originate in bats and rodents but can also jump into humans via an intermediate species such as camels or cows. Immune defences that we inherit, such as interferon-stimulated genes (ISGs), are important in determining whether we can be successfully infected by animal viruses. However, very few ISGs that specifically inhibit coronaviruses have been identified. Our lab has built a large library of ISGs from many species including humans, monkeys and cows and we will use this to test their antiviral activity against coronaviruses found in bats as well as coronaviruses that already infect humans. Since SARS-CoV-2 is unlikely to be the last animal coronavirus to transmit to humans, learning how these ISGs protect us from coronavirus infection will strengthen our understanding of the immune barriers that hinder the cross-species transmission of coronaviruses, and help determine the risk posed by animal coronaviruses to human health.",2021,2024,University of Glasgow,0,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Animal source and routes of transmission,2021 +C19400,224632/Z/21/Z,The role of capillary pericytes and LRP-1 in Parkinson's disease and dementia,"I previously showed that in Alzheimer's disease (AD) amyloid beta constricts brain capillaries via signalling to pericytes. I now wish to investigate: (1) Parkinson's disease (PD) / Lewy Body Dementia (DLB), where alpha-synuclein evokes ROS production and hypothesise that endothelin will be released (as observed in AD) and evoke pericyte-mediated capillary constriction to decrease cerebral blood flow. (2) The role of APOE receptor LRP-1 in regulating increased tau phosphorylation in AD. LRP-1 is a master regulator of tau uptake/spread and highly expressed on pericytes. In AD model mice, pericyte deficiency leads to tau pathology and early neuronal loss. Thus, pericyte LRP-1 may play an important role in clearing/processing tau in the setting of amyloid pathology. I will examine whether AD-like tau pathology develops in an APP knock-in AD/pericyte-LRP-1 deficient mouse model. (3) The effect of Covid-19 on live human pericytes and capillaries.",2021,2026,University College London,890814.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Other,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis,2022 +C19401,224485/Z/21/Z,Novel statistical methods to unlock the potential of routinely collected health data: COVID-19 & beyond,"The recent pandemic has highlighted the importance and great potential of electronic health record data for addressing urgent public health questions in a timely manner, while demonstrating key gaps in existing methodology for this setting. The overall aim of this proposal is to develop statistical methodology to remove barriers that have hampered important public health issues in COVID-19 being fully addressed; and to apply the methods to answer the immediate and arising public health questions in COVID-19 and more broadly. Key goals are to: develop a suite of methodological tools to enable computationally-efficient self-recalibrating risk prediction in EHR databases; develop a framework for assessing the worth of different treatments within EHR databases, accounting for potential high-dimensional confounding and implementing approaches to estimate individual treatment effects within this; create analytic approaches to address causal questions requiring data from two separate sources in the absence of full individual linkage. Data held within the OpenSAFELY platform and the UK Clinical Practice Research Database will be used to motivate the statistical methodological work. Optimal methodological approaches will be applied to address important questions arising in COVID-19 and more broadly, to key questions in chronic disease.",2021,2027,London School of Hygiene & Tropical Medicine,1907373.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2022 +C19402,224335/Z/21/Z,Society for the Social History of Medicine Events,"The Society for the Social History of Medicine has a strong track record of providing field-leading conferences in the history of medicine and health, together with postgraduate and early career training and events. Our proposed programme of new and innovative events will allow us to begin new areas of work in the areas of anti-racism, mid-career support, and discussions about career precarity. Wellcome funds will enable scholars to meet at a crucial time for the field, at a time when, with the continuing risk of Covid-19 and other disease outbreaks, the history of medicine has perhaps never been so vital. Bringing scholars together for physical meetings is essential to create the safe space needed for such sensitive discussions as anti-racism, facilitated by a clinical professional and academics experienced in this area, and regarding concerns about careers. The impact of Covid and changes in funding for universities mean many mid-career scholars are in need of support and mentoring, and those without permanent positions are in need of a safe space to discuss the future of the field and the impact on, and potential for, their own work and careers.",2021,2025,University of Strathclyde,35138.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19403,224243/Z/21/Z,New insights into children and young people's mental health derived from the interaction between the family ecosystem and the COVID-19 pandemic,"Children and young people's (CYP's) mental health is an urgent priority. Dramatic, socio-economic changes following the COVID-19 pandemic has already disproportionately affected families, and with economic uncertainty, further shocks are expected. This fellowship shall use epidemiology, biostatistics, causal inference and machine learning applied to high-quality psychiatric surveys to investigate how changes to the family 'ecosystem' affects CYP mental health. The first goal is to describe typical family ecosystems and assess CYP mental health in each. The second goal will be to conduct first network analysis of mental health symptoms within families using graphical networks. The third goal will be to estimate the effect of acute changes from the pandemic (e.g. school closures) on CYP mental health. Finally, longer term changes to the family ecosystem will be determined, then analysed to assess their effect on CYP. For the latter two, I shall use causal mediation analysis to determine modifiable determinants of mental health and interaction analyses to determine which children are vulnerable, and what modifiable factors could create resilience. A website disseminating findings and provided a children's mental health dashboard shall be co-created with a CYP advisory group.",2021,2028,University of Manchester,904111.62,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C19404,224190/Z/21/Z,"Integrating genomic, serological and epidemiological information to understand the emergence, spread and establishment of novel SARS-CoV-2 variants","Emergence of SARS-CoV-2 variants has underscored the importance of genomic surveillance in enabling timely identification of new viral threats, and the role of transmission modelling in characterising the public-health risk they pose. These analyses have largely been considered independently of each other during the pandemic however, despite evidence that genomic and epidemiological data can provide complementary insights into virus dynamics. I will develop a Bayesian transmission-modelling framework reconciling both data-sources and use this framework to systematically compare the epidemiological properties (e.g. transmissibility, disease-severity and immune-evasion potential) of key variants (including but not limited to Alpha, Beta, Gamma and Delta), across settings including Brazil, Colombia, India, Panama, South Africa and the UK. I will explore how the dynamics of variant establishment and spread are shaped by intrinsic variant properties and their modification by epidemiological context (e.g. control measures or levels of population-immunity), and examine whether there is evidence for different contexts influencing the establishment of variants with particular properties. This work will improve our understanding of the types of SARS-CoV-2 variants likely to establish and spread in the future; inform decisions aimed at mitigating their potential public-health impact; and provide insight into the ways epidemiological pressures influence viral evolution.",2021,2026,Imperial College London,414450,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Africa | Americas | Europe | South-East Asia,,,,United Kingdom,Brazil | Colombia | India | Panama | South Africa | United Kingdom,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures,2022 +C19405,224140/Z/21/Z,The Epiverse - Distributed Pandemic Tools Program,"Covid-19 exposed major gaps in our ability to aggregate and use data for pandemic prevention, detection, and response. Current approaches require pooled data, which is costly, time-consuming, and legally challenging. Distributed and privacy-preserving methods of analysis are an alternative for generating insight and present new opportunities to use commercially held ""health-adjacent"" data critical for pandemic analysis and modelling. However, despite the appeal of distributed and privacy-preserving methods of analysis, there are few working examples focused on disease analysis and none that are globally adopted. This proposal is to build, deploy, and scale innovative solutions - including infrastructure, tools, and analytical techniques to unlock data and enable distributed analysis. Phase 1 will focus on developing the novel software and privacy-preserving methods that will be deployed in Phase 2: Funding top teams to develop a suite of generalizable, open-source epidemiological software and tools Challenge funding call to develop privacy-preserving approaches for deployment on commercially sensitive/privately held data, which could be scaled and deployed in Phase 2. 200 Days Architecture Challenge aimed at Big Cloud Providers to design the technical architecture for Phase 2. data.org will provide the central convening and coordination role, including grant-making, convening interdisciplinary specialists, project management, and strategic communication.",2021,2024,New Venture Fund,3003756.16,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2021 +C19406,224028/Z/21/Z,Economic analysis of health impacts of carbon pricing on land-use,"The proposed work is - to our knowledge - the first integrated economic analysis of a single policy intervention and its potential to influence three interlinked threats: the global health crises of both non-communicable diseases and new infectious diseases such as Covid-19, as well as environmental degradation, including biodiversity loss and climate change. The work will comprise modelling the consequences of carbon pricing, set at a level compatible with keeping climate change within planetary boundaries, with outcomes including land-system change, agricultural production, food prices, diets and health outcomes, and effects on infectious disease and biodiversity. The analysis will consider potential differential effects of carbon pricing across socio-economic groups, and between high, medium and low-income countries, as a basis for considering policy interventions to mitigate inequitable outcomes. This analysis will contribute to the goal of The Lancet-Chatham House Commission which is to identify actions that can impact positively across the shared drivers of the three threats to human and planetary health described above. Importantly it will provide novel evidence for the ways in which co-benefits and co-costs of interventions might form a significant part of the political and economic cases for intervening at national and international levels and optimising policy design.",2021,2021,University of Cambridge,68230,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C19407,224021/Z/21/Z,"Development of an investigational new drug from a novel, open-science, orally available small molecule antiviral targeting SARS-CoV-2 main protease","The COVID Moonshot project focuses on global equitable access to a safe, low-cost oral antiviral treatment that quickly clears SARS-CoV-2 infections and future coronavirus-related diseases. Current therapeutics in clinical trials require intravenous administration and are developed mainly by organizations focusing on a commercial return. This proposal will research an oral treatment to significantly improve patient outcomes in low-resource settings, removing the need for a cold chain or injection and enabling stockpiling of therapeutics for both this and future pandemics We will develop a novel inhibition of main protease (3CL protease) of coronaviruses in order to prevent viral replication, aiming to create a generic drug ""straight from the pipeline,"" facilitating decentralised manufacturing and distribution allowing for rapid patient access. We target effective oral treatment for early stages of disease to reduce viral load, mortality and morbidity (e.g. long COVID). The goal is to progress a compound to Phase I readiness, anticipating clinical trials in 2022. This proposal involves the established Moonshot team complemented by DNDi's expertise in IP and access strategy, preclinical project management, and drug development. The project aims to maintain the proven open science model adopted from the outset.",2021,2023,Drugs for Neglected Diseases Initiative,9994019.27,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19408,223814/Z/21/Z,ISOPLEXIS platform for single cell multiplexed functional proteomics of immune cells,"The IsoPlexis IsoLight platform is a unique, highly multiplexed single-cell microchip proteomics technology applicable to both basic and clinical research. Quantitative measurement of secreted proteins associated with a broad range of functional profiles is derived from over 1000 live single cells using intracellular protein detection via high-density antibody barcode arrays. It can precisely dissect the functional heterogeneity ('polyfunctionality') of immune cells with genetically and phenotypically identical signatures and several studies have shown that polyfunctionality determined at the single-cell level can identify critical effector cells associated with durable immunity against infections and cancer. Isoplexis analysis of polyfunctionality in the cell therapy space reveals that phenotypically similar T-cells can have heterogeneous functions and that the 'polyfunctionality index' can provide predictive signatures for toxicity and response to treatment. This state-of-the-art equipment will be housed at the UCL Royal Free Campus and will be used primarily for disease-focused and translational immunology research spanning the disciplines of immunotherapy, autoimmmunity, immunodeficiency, infection (including COVID-19) and cancer. This breakthrough single cell proteomics analysis platform will enable immunology and immunotherapy scientists at UCL to further enhance their understanding of endogenous and engineered human immune cells subsets in the pathophysiology of disease and in the response to treatment.",2021,2024,University College London,144590.33,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C19409,223739/Z/21/Z,PDBe-KB - enhancing impact of structural knowledgebase in basic and translational research with focus on Pathogenic Mutations,"Established in 2018, the PDBe Knowledge Base (PDBe-KB, pdbe-kb.org) is a community-driven resource providing FAIR access to experimental and predicted 3D structure models and enhanced structural and functional annotations e.g. predicted functional sites. PDBe-KB supports fundamental biology, biomedicine, biotechnology and bioenergy by enabling atomic-level understanding of macromolecular function through its novel, consolidated presentation of all the available structural data and enriched annotations by means of ""aggregated views"". The PDBe-KB consortium has established common data standards for structural and functional annotations to improve data interoperability extending the impact of structural data e.g. to rationalise the impacts of disease-associated mutations, and thereby assist diagnostic and therapeutic strategies. In this project we will: Grow the PDBe-KB consortium to broaden the structural and functional annotations with specific emphasis on integrating residue mutation data in human and pathogen genomes. Establish a new and comprehensive 3D-fold structure domain library (3D-SCAfold) through integration of CATH and SCOP domain data. Ten-fold increase in the structural coverage of the sequence space using 3D-SCAfold for enhanced structure-based annotations with a specific focus on disease genotype data from human disease and pathogen proteins (e.g. SARS-CoV-2, Mycobacterium tuberculosis). Develop novel visualisation tools, and a collection of aggregated views.",2021,2027,European Bioinformatics Institute,1447684.3,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +C19410,223733/Z/21/Z,"Preparing for disease X, the next pathogenic respiratory viruses: the development of cross-reactive nanobodies for diagnosis, prophylaxis and treatment of coronavirus infections.","We will address the urgent and unmet need within the biomedical community for effective agents to combat the existing threat from coronaviruses and to be prepared for those that will arise in the future. We will also deliver a pipeline that will be applicable to other high threat respiratory viruses (Disease X). We propose to build a nanobody screening strategy that targets cross-reactivity from which we anticipate identifying (pan)-coronavirus binders. The pipeline will combine nanobody technology, structural biology and virology making use of the Diamond synchrotron at Harwell for X-ray data collection and the CL3 facilities in Oxford and Liverpool for handling live viruses. Together the results will enable the structure-activity relationships of anti-coronavirus nanobodies to be determined providing information that will guide sequence changes to increase nanobody binding and counter the effects of virus escape mutants or natural variants on virus detection and neutralisation. The demonstration of in vivo potency to SARS-CoV-2 and other than coronaviruses(cross therapeutic) is a key aim of the proposal and we will test any new potent neutralising nanobodies in an appropriate disease model.",2021,2024,Rosalind Franklin Institute,1297509.17,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +C19411,223705/Z/21/Z,Expansion and support of SARS-CoV-2 sequencing in West and Central Africa to support the COVID-19 pandemic response,"The recently emerged SARS-CoV-2 variants of concern (VOC) have altered transmissibility, virulence and susceptibility to neutralising antibodies, leading to concern over the potential for new variants to emerge that have increased resistance to vaccine-induced immunity. This has led to a renewed focus on the deployment of whole-genome sequencing surveillance to detect variants early, to stop or slow their spread, and to enable vaccine programmes to adapt. However, despite increased genome sequencing, disparity in access to laboratory support and genomic sequencing across the globe has become increasingly evident: to date West and Central Africa produced ~2,000 sequences ( 400,000 from the UK. The VOCs such as P.1 in Brazil and B.1.351 in South Africa can emerge anywhere, further highlighting the urgent unmet need to develop sustainable solutions for COVID-19 sequencing in this underserved region. This proposal builds on the experience of the ARTIC network and regional collaborators to support SARS-CoV-2 sequencing in West and Central Africa. The key goals of this proposal are to: Develop a hub and spoke network of SARS-CoV-2 sequencing labs in West and Central Africa. Develop a suite of COVID-19 focused training materials and tools for whole-genome sequencing and subsequent data analysis.",2021,2023,University of Cambridge,3117546.06,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Health Systems Research | Research on Capacity Strengthening,"Medicines, vaccines & other technologies | Systemic/environmental components of capacity strengthening",2021 +C19412,223703/Z/21/Z,Exploring global and regional approaches for violence against women research priority setting,"The global covid-19 pandemic has highlighted the scale of violence against women (VAW), and how far we still have to go to prevent VAW and provide quality responses to victims/survivors. Priority setting processes are an essential part of aligning funding with knowledge gaps. However, processes vary globally, are often not inclusive, and often dominated by the interests of funders in the global north. The Sexual Violence Research Initiative (SVRI) is the largest network for VAW research, providing an essential platform to share research and connect. Engaging with the SVRI's extensive networks, the key goal of this project is to engage global and regional groups in a discussion about the utility and efficacy of priority setting processes. This will be achieved by creating a space where priority setting processes can be critically examined with an emphasis on decolonising these processes and standardising priority setting methods to improve VAW research moving forwards. The outcome will be a co-produced set of global principles for research priority setting which embody what has been learnt during the pandemic, reflect the work of regional and global groups and ensure that intersectional voices, including voices from researchers in low and middle income countries, are heard and represented.",2021,2022,Institute of Development Studies,15629.92,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Gender,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +C19414,223679/Z/21/Z,Mass-Observing Covid-19,"Mass-Observation (M-O) has been recording everyday life in Britain since 1937. Since the start of the Covid-19 crisis, we have collected over 8500 pieces of narrative life writing, ranging in format from open-questionnaire responses and day diaries to diaries kept for several months by self-selecting volunteers of all ages from around the UK. This unique set of large-scale qualitative data offers extensive research value and potential to contextualise quantitative data generated throughout the pandemic. This project will open up the extensive collections of qualitative data relating to the impact of Covid-19 on the mental and physical health and social welfare of volunteer writers around the UK. We will build a tool for discovery and exploration that allows researchers to interrogate these collections. A database will comprise metadata on the writers and writing that enables researchers across disciplines to interrogate the content of the data, thereby contributing to our understanding of the social and personal impact on UK health and wellbeing during the Covid-19 pandemic. The tool is designed to open up access to the texts that have been submitted, allowing researchers to select relevant materials and export the data into their own choice of research tools for analysis.",2021,2023,University of Sussex,250930.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19415,223675/Z/21/Z,The Archive of Tomorrow: Health Information and Misinformation in the UK Web Archive,"This pilot project will preserve and provide research access to 10,000 websites relating to health information (and misinformation), and will use this collection to enable more health research on the UK Web Archive. Our project brings together four co-applicant institutions, and a network of other organisations and researchers, to tackle one of the most pressing research issues of our time: how can the story of changing online health information be captured and understood? During the Covid-19 pandemic, online health advice, data and scientific evidence have been contested, revised, used and mis-used with global consequences - but the digital record of this activity is fragile and hard to access. We will: Curate a new research-ready collection of websites within the UKWA, with the theme of Health Information and Misinformation, ensuring a wide representation of diverse and otherwise under-collected sources. Use this collection as a test-bed to explore options for metadata, computational analysis, ethics and rights issues. Build a research network across disciplines including use cases, involving researchers in the process of building, evaluating and using collections. Produce a project report with recommendations for future work and advocacy for change to make web archives more representative, inclusive and open for health research.",2021,2023,National Library of Scotland,321724.49,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Communication,2022 +C19416,223668/Z/21/Z,Reducing moral stress in veterinary teams? Evaluating the use of ethical discussion groups and ethical decision making tools in veterinary practice.,"Vets regularly experience ethical dilemmas when balancing the needs of animals, their owners and financial constraints. Moral stress, described as a feeling of conflict over what care it is appropriate to provide, may even contribute to the heightened risk of suicide observed in the veterinary profession. Charitable veterinary providers such as PDSA are currently working under extremely challenging conditions, with reduced capacity and increased demand caused by the COVID-19 pandemic. Whilst ethical discussion groups and the use of ethical decision making tools have been proposed for supporting veterinary decision making, such practices have yet to be evaluated for their effectiveness in veterinary rather than equivalent human medical teams. I will pilot the use of an ethical decision making tool within a supportive group environment to help PDSA veterinary teams explore their approaches to ethically challenging cases. Through in depth interviews, I will invite veterinary team members to share their experiences of moral stress and evaluate the effectiveness of small group structured ethical discussions. My research will help PDSA develop strategies for improving veterinary mental health through supported ethical decision making. The research will also help us to better understand the causes and effects of moral stress in veterinary teams.",2021,2022,University of York,62010.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Veterinarians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C19417,223651/Z/21/Z,Emergency oxygen response for COVID-19,"The O2 Taskforce is coordinating access to emergency oxygen for COVID-19 patients in LMICs. Since the start of the pandemic, affordable, sustainable access to oxygen has been a growing challenge LMICs. COVID-19 has put huge pressure on health systems, with hospitals running out of oxygen, has resulted in preventable deaths and huge burden on families of hospitalized patients. Oxygen is an essential medicine, and despite being vital for the effective treatment of hospitalized COVID-19 patients, access in LMICs is limited due to cost, infrastructure and logistical barriers. The O2 Taskforce has identified an immediate need of approx. US$ 90 million over the next 1 - 2 months, with a US$1.6 billion need estimated for LMICs over the next 12 months to support. The proposal will secure funding ($10 million) for acute oxygen COVID-19 needs in LMICs as identified by the O2 Taskforce. The funds will support countries to access oxygen and to unlock available resources to build more sustainable, resilient oxygen systems. Activities may include technical assistance for implementation of oxygen services, investments for market interventions and for additional country assessments/development of country funding proposals. This investment is intended to accelerate and amplify the impact of follow on scale-up funding.",2021,2022,"World Health Organization, Switzerland",9890555.3,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Switzerland,Switzerland,Clinical characterisation and management | Health Systems Research | Research on Capacity Strengthening,"Supportive care, processes of care and management | Medicines, vaccines & other technologies | Cross-cutting",2021 +C19418,223648/Z/21/Z,Kept on Ice: Exploring international blood stem cell donor perspectives on the practice of unanticipated cryopreservation,"When people register as blood stem cell donors, they do so to save a stranger's life. However, on rare occasions, donated tissue does not go on to clinical use, potentially being cryopreserved indefinitely. This presents a socioethical conundrum for registries, who have to make a decision about the future of this tissue, e.g., should it be destroyed, or used in therapeutic research? This secondment fellowship is a collaboration with Anthony Nolan, the world's first blood stem cell, or bone marrow, registry. The secondment topic, co-produced with Anthony Nolan, is an exploration of this issue, which has become urgent as COVID-19 has increased instances of unanticipated cryopreservation globally. The secondment fellowship comprises (i) exploration of perspectives of international stem cell donors on the potential futures of cryopreserved tissue beyond the clinic through focus groups with donors, and (ii) generation of critical social science to be disseminated to registries around the world through a report for practitioners. Findings will generate knowledge to inform global practice regarding cryopreservation, and the use of donor stem cells in therapeutic research. The secondment aims to build collaborative relationships with non-academic organisations for future social science research on the global stem cell infrastructure.",2021,2022,University of Sheffield,46947.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues in the Allocation of Resources | Other secondary impacts,2021 +C19419,223620/Z/21/Z,Diversity Amongst Decision Makers?: Black & Minority Ethnic (BME) Representation in Pandemic-Era NHS Management,"Though Black and Minority Ethnic (BME) populations have been significantly overrepresented in COVID-19 mortality statistics, they are vastly underrepresented in NHS management. It is critical to address this lack of diversity amongst decision makers to ensure equitable representation, as current NHS leadership is not adequately representative of the workforce or communities for whom it cares. Principally this project asks: what is the scope and capacity within non-clinical NHS management and NHS decision-making to understand and address BME healthcare worker experience in the face of emerging and changing health care structures, and how can it be improved for the future of equitable health service delivery and diversity in the workforce? Working with the Nuffield Trust, key project goals are: Investigate the current understandings and approaches to race and ethnicity within non-clinical London NHS Management teams. This will be achieved through embedded ethnography within 1-3 London NHS Trusts; chosen for diversity of workforce. Encourage more open dialogue to navigate ethnic and racial concerns when it comes to mitigating COVID-19 and other future health risks. This will be achieved through an open-access, widely available report and associated workshop-toolkit that will be published online and circulated to management teams and stakeholders.",2021,2022,University College London,43337.69,Human Populations,Asian | Black | Other,Adults (18 and older),Unspecified,Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2021 +C19420,223613/Z/21/Z,Genomic surveillance of SARS-CoV-2 and nationwide capacity building across Bangladesh,"Our proof-of-concept study used MinION (Oxford Nanopore Technology), ""Lab in a suitcase"" to generate genomic data that we combined with mobility data mobile phone operators to provide an early picture of the dynamics of the COVID-19 epidemic in Bangladesh. We showed evidence of repeated introductions by returning migrant workers and international travelers leading to the emergence and rapid country-wide dissemination of SARS-CoV-2 lineages or variants. Bangladesh urgently needs an integrated genomics network suitable to identify and track known or novel variants. Our proposal is to establish a country-wide network for SARS-CoV-2 genomic surveillance. We will do this by extending the number of MinION-based sequencing platforms to seven federated sites linked to the Ministry of Health and Family Welfare, representing facilities in different administrative areas (6 of 8) comprising Bangladesh. The advantage of these devices is their portability and ease of use, and the flexibility of the platform beyond SARS-CoV-2 in the context of future epidemics. We will use the expertise we have developed to train researchers, adopting a ""train the trainer"" model of capacity building, in sequencing, bioinformatics, and epidemiological modeling, such that we are able to respond to COVID-19 as it evolves, as well as to future pathogen threats.",2021,2023,Institute of Epidemiology Disease Control & Research,651027.46,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,South-East Asia,,,,Bangladesh,Bangladesh,Epidemiological studies,Disease transmission dynamics,2022 +C19421,223488/Z/21/Z,Decolonization and global health research: initiating an African centred exchange,"This award will support a series of interactions between academics from diverse backgrounds with a shared interest in mapping, analyzing and critically unpacking decolonization debates in global health research. Decolonization discussions and activism have become far more prominent over the last year, bringing both opportunities for positive transformation (through disruption, change and renewed interest in global power inequities) as well as challenges (including the 'trending' of the decolonization agenda leading to - at worst - the 'colonization' of the arena itself). Now, as much as ever, decolonization discussions and debates need to be critically examined. We will organize a set of exchanges and activities to: 1 Unpack and reflect upon the term 'global health research' using a decolonization lens; 2 Examine how tacit, or embedded, forms of knowledge from Africa are drawn upon and feature in global health research; 3 Imagine what a decolonized or African-centred, and ethical, research initiative in global health might look like; and 4 Share our learning, advocate for change, and identify an African home for future work. We will incorporate a covid-19 research lens, but only in recognition that covid-19 will shine a light upon or amplify far longer and deeper policies and processes.",2021,2023,University of Oxford,272267.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Research to inform ethical issues | Research on Capacity Strengthening,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Cross-cutting",2021 +C19422,223377/Z/21/Z,Embodied Inequalities of the Anthropocene. Building Capacity in Medical Anthropology,"This collaboration between Brazil, Mexico and the UK brings together environmental, indigenous, biosocial, multispecies, gender and theoretical expertise in Medical Anthropology, to extend interdisciplinary engagement concerning how the Anthropocene epoch impacts on human health. Supported by a post-doctoral researcher in each of the collaborating centres, we will develop Medical Anthropology in four areas: i) indigenous experience and coloniality of the Anthropocene, ii) gender, reproduction and environmental justice, iii) multispecies ethnography and human-animal health, iv) COVID-19 and public understanding of the Anthropocene. From this research and in conjunction with open access publisher UCL Press, we will develop a tri-lingual digital resource for teaching and public reference. Our collaboration will begin online with bi-monthly meetings followed in February 2022 by a three day virtual cross-disciplinary seminar with invited expertise in science, geography, politics and history. We will work collaboratively to examine how these disciplines can inform Medical Anthropology of the Anthropocene and to identify articulations with policy and practice as these impact on human and environmental wellbeing. In November 2022 we will hold a face-to-face workshop in Mexico to develop dissemination and publications including the digital teaching resource and a multilingual special edition of a Latin American Medical Anthropology journal.",2021,2023,University College London,275529.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Americas | Europe,Gender,,,United Kingdom,United Kingdom | Brazil | Mexico,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Systemic/environmental components of capacity strengthening,2021 +C19423,223326/Z/21/Z,Filling in the gaps during a crisis of care: social and political constructions of lay care work during the HIV/AIDs epidemic and the Covid-19 pandemic in South Africa.,"The project aims to explore the various social and political constructions of lay care work during the Covid-19 pandemic and the early stages of the HIV/AIDs epidemic in Cape Town. It will analyse the tensions and possibilities that arise when informal, self-organised and localised care work done by ordinary people interacts with the formal health system, considering how this represents a potential for social change in the health system and broader society. Analysis will draw on Feminist care theory and De Certeau's concept of tactics and strategies, situating the project in a broader critique of the ways in which the dominant neoliberal and capitalist order produces a crisis of care that marginalises care work and stifles possibility for meaningful collaborations between the formal health system and ordinary people doing this work. Research will involve archival and document-based data such as meeting recordings, media pieces, policy documents, academic and NGO reports, and documentary films regarding lay care work and community-based care during Covid-19 and the early stages of the HIV/AIDS epidemic (90s-early 2000s). It will also draw on in-depth interviews with participants who were actively involved in and/or able to reflect on the provision of place-based, lay care during both cases.",2021,2024,University of the Western Cape,116304.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Africa,,,,South Africa,South Africa,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C19424,223195/Z/21/Z,Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV),"We propose to set up and validate a pharmacometric platform to provide quantitative assessment of antiviral effects in low risk adult patients with recent onset uncomplicated COVID-19 and high viral burdens. This assessment is based on measurement of oropharyngeal viral clearance rates. This will be a randomised, open label, group sequential adaptive platform trial to quantitate the antiviral activity of currently available potential (i.e. repurposed) treatments in low-risk adult patients with early COVID-19, through adjusted qPCR of serial oropharyngeal samples. It will be a mainly outpatient study conducted in three locations; one each in the Americas, Europe and Asia. The interventions to be evaluated in this first phase are hydroxychloroquine, lopinavir/ritonavir, ivermectin, miglustat, remdesivir, intranasal heparin, with the Regeneron monoclonal antibody cocktail or Peginterferon-lambda as a positive control. This will identify drugs with a > 90% probability of accelerating virus clearance compared to no treatment and will reject drugs with",2021,2023,University of Oxford,5088336.86,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2021 +C19425,223164/Z/21/Z,Translational genomics in critical care medicine.,"My work during the Covid outbreak has shown that genetic associations with critical illness can predict therapeutic targets, and that therapies targeting the host response improve outcome in carefully-defined subgroups of critically ill patients. I propose to extend this work to bridge the gap between genetic discovery and therapeutic application. In doing so I will build on established infrastructure and lay the foundations of a system for rapid identification and assessment of candidate drugs for respiratory critical illness. To achieve this I will: Use genome-wide association studies to identify host genes associated with critical illness in viral pneumonia (Covid-19: 20,000 cases; influenza: 3000 cases). Identify targets using computational approaches including integrated functional genomics and Mendelian randomisation. Complete proof-of-principle analysis to test for differential genetic effects in new patient subgroups. Refine and test candidate causal variants in vitro. Establish technology for distal lung regional microdosing to validate targets in vivo in critically ill humans. At the end of this fellowship I will have established a programme of translational genomics in critical care medicine going from genomic discovery to experimental medicine in humans.",2021,2026,University of Edinburgh,2317807.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation",Disease surveillance & mapping | Prognostic factors for disease severity,2021 +C19426,223107/Z/21/Z,Reversible ADP-ribosylation signaling in the control of coronavirus infection,"The interferon (IFN) immune response induces an antiviral state by triggering the expression of IFN-stimulated genes and is the primary line of defence against infection. The proteins encoded by these genes fulfil a variety of functions, including degradation of viral RNA and reduction in protein translation. Unsurprisingly, viruses have evolved compensatory mechanisms to suppress the IFN response. One such family of viruses is Coronaviridae, responsible for the current COVID-19 pandemic. Suppression of IFNs by Coronaviridae has been attributed to the macrodomain module present within the multidomain Nsp3 protein. The macrodomain functions as an ADP-ribosylhydrolase to neutralise the actions of the antiviral members of the poly(ADP-ribosyl)polymerase (PARP) family. However, the mechanisms through which antiviral PARPs and macrodomains impact the IFN response remain unclear. This proposal will provide a molecular understanding of how antiviral PARPs suppress coronavirus infection and how SARS-CoV-2 macrodomains oppose their activity to evade IFN signalling and promote viral replication. Furthermore, comparative analyses of the macrodomains from different coronaviruses and their impact on interferon response may explain the variations in their pathogenicity. Collectively, our studies will inform interferon-based disease management strategies to prevent spread within and between infected hosts and provide novel biomarkers of susceptibility and antiviral drug targets.",2021,2026,University of Oxford,1710411.86,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +C19427,223099/Z/21/Z,Improving the treatment of tropical infectious diseases,"In the final three years of my Principle Fellowship I wish to complete studies to improve the treatment and elimination of malaria. To counter the threat of antimalarial drug resistance emerging from the Greater Mekong sub-region I have recommended a switch to triple artemisinin combination treatments and developed the methods to conduct targeted malaria elimination in endemic areas. I propose a series of studies to assess the safety, efficacy and overall benefit of these new approaches. To support control and elimination I will develop and evaluate better methods of identifying, measuring and monitoring antimalarial drug resistance. To prevent relapses of vivax malaria (the main therapeutic challenge and obstacle to elimination) I will investigate safer methods of giving primaquine, and identify the optimum dose of tafenoquine. I will improve methods for the pharmacometric assessment of antimalarial drugs and I will apply similar proven principles to the assessment of much needed treatments of Chagas disease and COVID-19. I will develop a pharmacometric platform based on assessment of parasite and virus clearance rates respectively for assessing and comparing new drug treatments. This is necessary to inform the choice of drug and dose in larger phase 3 assessments, accelerating their development.",2021,2025,University of Oxford,3635637.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Phase 3 clinical trial | Prophylactic use of treatments | Therapeutic trial design,2022 +C19428,223080/Z/21/Z,Advancing the global health agenda with the Paris Peace Forum,"The Paris Peace Forum will host a series of discussions to maintain the partnership developed by ACT-A (Access to COVID-19 Tools Accelerator) and the governance of global health at the top of the political agenda and further deliver concrete solutions while contributing to the construction of an overall governance framework in the sector. The proposal includes hosting discussions taking place in the framework of a pilot, year-long partnership between the Forum and Wellcome Trust. These discussions would mobilize stakeholders of the Forum's community and beyond. The Forum would naturally seek Wellcome's guidance and advice on the scope, topics, invitees, and outputs of these discussions. Stakeholders would be invited to participate in each discussion based on their institutional focus and expertise and on the basis of their capacity to contribute to and implement the desired outcomes. With the support provided by the Wellcome Trust, the Forum could convene two roundtables in 2021, to provide for sufficient time for preparation, eventually for follow-up actions in between and potentially to leverage to key moments in the annual Forum cycle: the Spring meetings of the Paris Peace Forum (May 2021) and the fourth edition of the annual event (11-13 November, 2021).",2021,2022,Paris Peace Forum,116244.82,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,France,France,Health Systems Research,Health leadership and governance,2021 +C19429,223054/Z/21/Z,'Trim-Away': Targeted Degradation of Proteins & Pathogens,"We wish to determine how the cytosolic antibody receptor and E3 ligase TRIM21 uses its potent antiviral and immune signaling activity to prevent infection by diverse viruses. We will use our newly developed protein deletion technology 'Trim-Away' to determine the ubiquitin machinery necessary to synthesize the diverse ubiquitin chain types that allow TRIM21 to drive proteasomal degradation of viruses and trigger innate immunity. We will build on our structural studies of TRIM21 to define the mechanism by which its pro-inflammatory signaling is regulated and how other ligases and deubiquitinases are recruited. We will exploit our recent discovery that TRIM21 promotes antigen presentation, by investigating its role in targeting antigens for proteasomal degradation and stimulating protective T cell responses during LCMV, Influenza and SARS-CoV-2 infection. Together this work will define new roles for TRIM21 in host immunity and decipher how TRIM21 uses ubiquitin to provide antiviral protection. The insight we learn from these natural mechanisms will further the development of new technologies like Trim-Away and may inform future antiviral and vaccine development.",2021,2026,Medical Research Council,2587991.93,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +C19430,223032/Z/21/Z,THE ARM RACE: HOW WE CONQUERED COVID (WORKING TITLE),"""THE ARM RACE: HOW WE CONQUERED COVID"" (working title) is a documentary film that will be the dispositive chronicle of the global race to research, develop, manufacture and distribute COVID-19 vaccines in the most enormous coordinated effort ever undertaken. In this unprecedented moment in history, the film will celebrate the herculean efforts of the scientific, research and immunization community during a complex time of mistrust, vaccine hesitancy, and misinformation - when trust in science itself has come under fire. The stories track development of vaccines, (including research built on previous work fighting outbreaks including Ebola and HIV/AIDS,) and how public health agencies from hospitals to the WHO are responding to the crisis. Our narrative goes beyond the lab, delving into the complexities of underserved populations, equitable access and inclusion. We see opportunities in additional content, leveraging existing assets, foregrounding the making of the film and our collaboration with the global public health community. This project will spark interest in science's potential to solve global health challenges by documenting the largest public health effort in human history, while also offering insights into our successes and failures to help prepare the next generation to better respond to future pandemics.",2021,2022,Utah Film Center,322093.36,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19431,223016/Z/21/Z,"Can we develop a ""cognitive vaccine"" for intrusive memories of traumatic events from working in the COVID-19 pandemic? A novel and brief intervention to support ICU staff","Intensive care unit (ICU) staff face repeated exposure to traumatic work-related events and have reported high levels of posttraumatic symptoms during the pandemic. Novel, scalable and preventative interventions are required. We are developing a ""cognitive vaccine"" approach for ICU staff against one key symptom - intrusive memories of traumatic events. These are unwanted, distressing and disrupt functioning. Our novel, brief gameplay intervention is repeatable, flexible, non-stigmatising, scalable, and driven by mental health science. This digital intervention is guided by an initial session of psychologist support, then self-administered; delivered same day or months post-trauma, suitable for repeated trauma exposure, fits with busy lives of ICU staff, without discussing trauma detail. Part 1 uses a Bayesian design to optimise and co-develop procedures with ICU professionals and move at speed under pandemic conditions, allowing limited rollout (guided-version) in these unprecedented times. Part 2 uses a pragmatic RCT (three arms: guided/non-guided/attention-control) testing clinical effectiveness and acceptability to inform clinical practice. If the non-guided intervention is effective (i.e. no psychologist support) it will accelerate the speed of rollout. Meanwhile through global mental health workshops with stakeholder communities we seek to understand the views of various communities worldwide regarding implementation of this novel intervention form.",2021,2023,P1vital Products Ltd,1243101.47,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19432,222887/Z/21/Z,UCH photography exhibition,"Produce, print and install an exhibition of photographs by Tom Pilston documenting University College Hospital (UCH) staff working on the Covid pandemic. Exhibtion to be in UCH lobby in Euston Road",2021,2021,Panos Pictures,2729.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Health Systems Research,Health workforce,2021 +C19433,222698/Z/21/Z,Development of small molecule inhibitors of the SARS-CoV-2 protease PLpro for the treatment and prevention of Covid-19,"The SARS-CoV-2 pandemic is a global health emergency that highlighted the need for new antiviral medicines and better pandemic preparedness. Our drug-discovery program focusses on a critical protein present in all coronaviruses, the papain-like protease PLpro. PLpro is essential for viral replication, but also stops our alarm systems to respond to viral infection, To achieve the latter, it removes 'ubiquitin' and ubiquitin-like signals required for inflammation and anti-viral signalling. Our world-leading experts in ubiquitin research, drug-discovery and infectious disease biology have leveraged our state-of-the-art facilities to identify new drug candidates to block PLpro. We have screened > 400,000 small molecule compounds and identified new chemical scaffolds that inhibit PLpro from SARS-CoV-2 without affecting human enzymes. Our program will deliver new antivirals to prevent or treat COVID-19 and also develop a library of efficacious drug candidates to combat future coronavirus outbreaks",2021,2022,Walter and Eliza Hall Institute of Medical Research,681600,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Western Pacific,Western Pacific,,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19434,222624/Z/21/Z,"Ready2Respond, a public-private collaborating platform to address pandemic preparedness gaps in lower income countries","Early 2019, a group of global health leaders with expertise in influenza, vaccinology and pandemic preparedness convened in London, for a Wellcome Trust-supported ""Shaping Meeting to explore the value of a coordinated work plan for epidemic and pandemic influenza vaccine preparedness."" Ready2Respond was formed as a global collaboration of partners committed to enhancing lower income countries' readiness to respond against influenza and respiratory viral pandemics. With a Secretariat established at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza preparedness, these priorities now include COVID-19. Three Expert Working Groups will design and execute cross-collaborative projects within three strategic priorities. Burden of Disease Risk Communication and Community Engagement Vaccine Access Ready2Respond seeks an initial grant from the Wellcome Trust of US$ $196,650. This initial grant will allow to: retain a Director, tasked with developing a comprehensive action plan with potential projects to start in 2021. execute a mapping study of organizations and agencies working on global seasonal and/or pandemic vaccine preparedness to ensure the relevance of Ready2Respond's mission and activities in the preparedness ecosystem. support communication activities to secure funds for identified projects from potential partner organizations.",2021,2021,Task Force for Global Health,201002.85,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health leadership and governance,2021 +C19435,222525/Z/21/Z,Putting bioethics at the heart of WHO and beyond,"The WHO Global Ethics Unit is part of the newly formed Science Division and would like to capitalize on the potential of the division and the global leadership shown by the team during the current COVID-19 pandemic, to truly embed ethics at the heart of decision-making at WHO. This proposal focuses on adding value to our current work programme. Additional technical and coordinating capacity will allow us to better leverage our vast bioethics networks and collaborative partnership with bioethics groups around the world to: support regional and in-country bioethics capacity needs; further develop a community of ethics experts; develop the global ethics agenda and focus on key areas of unmet or continuing need, including health emergency preparedness and response. Additional resource will also allow us to be more responsive to demand set by the WHO and global research and health communities.",2021,2024,"World Health Organization, Switzerland",2437620.46,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Switzerland,Switzerland,Research to inform ethical issues,Research to inform ethical issues in Governance,2022 +C19436,222516/Z/21/Z,RNA processing and degradation,"All living systems - cells or organisms - operate in and must adapt to constantly changing environments. RNA transcription, processing and assembly with protein complexes form the core of the gene expression system, but many key features remain unclear. At times, very substantial changes take place; for example, in response to sudden environmental changes, following infection or during developmental progression. To address unresolved questions in RNA biology, we developed biochemical techniques to identify key, relevant RNA-protein, RNA-RNA and protein-protein interactions. These will be improved and applied in the proposed work, supported by bioinformatics. RNA systems are highly conserved in evolution, so techniques developed in yeast can be adapted for human cells and applied to understand disease. RNA biology in a cellular context is subject to dynamic changes. Kinetic analyses will therefore be applied, particularly during changes in cell state. Specific topics: 1: How is the nascent RNA linked to transcription termination and RNA processing 2: How does RNA metabolism respond to environmental stress? 3: How is host RNA metabolism remodelled during Coronavirus infection? 4: What are the roles of ncRNAs in neuronal development? The insights generated, and the experimental and bioinformatics techniques developed, will underpin future work by many groups.",2021,2026,University of Edinburgh,3788068.98,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C19437,222499/Z/21/Z,Evaluating Policy Implementations TO Predict MEntal health [EPITOME]: a Bayesian hierarchical framework for quasi-experimental designs in longitudinal settings,"Mental health problems are a leading cause of ill-health, with 1 billion experiencing mental health or substance use disorders worldwide. In the UK, anxiety and depression contributed 8% of the years lived with disability in 2017 and are associated with the second largest costs to society after dementia. This morbidity is accompanied by substantial suicide mortality, which rose by 10.8% in 2018, with even faster rises amongst young people. Socio-economic disadvantage is strongly associated with mental ill-health. Austerity and immigration policies (i.e. systemic ""shocks"") implemented in the UK since 2010 may have increased mental health problems, particularly in disadvantaged populations, including people from ethnic minority backgrounds and may have been further exacerbated by the COVID-19 pandemic. However, causal evidence is missing. Data typically available to evaluate such issues are observational (without random allocation) and population-wide (without controls), biasing straightforward estimation of causal effects. To advance causal inference of systemic shocks (policies, COVID-19) on population health outcomes, we will develop a generalisable statistical framework to overcome biases inherent to observational data. We will then apply this to evaluate the cumulative long-term causal impact of these shocks on mental health outcomes using longitudinal and spatial data, with particular focus on ethnic inequalities.",2021,2025,University College London,910666.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19438,222489/Z/21/Z,Design and implementation of a translational drug development platform for COVID-19 to generate preclinical evidence in support of treatment arms of the ANTICOV clinical trial,"Through the rapid establishment of a translational pathway, DNDi and its partners aim at providing the next generation of candidate medicines for SARS-CoV-2 clinical trials as well as integrating back-translations to validate the most appropriate preclinical models. The project is planned to run from September 2020-December 2021, with a total budget of 1.97M GBP, split into three pillars of activities composed of short and medium- term deliverables: Pillar 1 : Selection of the best combination of repurposed antiviral drugs to include into the 3rd arm of the ANTICOV clinical trial and the next back-ups Pillar 2 : Support candidate progression through an integrated pharmacometrics package involving both Physiologically-Based Pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modelling approaches Pillar 3 : Development of a translational platform and performance of a comparative analysis of selected drugs/combinations (including those from Pillar 1) to better understand and refine the screening cascade with best translational value; definition of a Target Candidate Profile (TCP) for SARS-CoV-2 mild infection This project will cement a collaborative partnership in the SARS-CoV-2 translational space that will pave the way to future longer-term discovery projects and preparedness for additional future threats. Key words: COVID-19 / Drug re-purposing / Translational drug development pathway",2021,2022,Drugs for Neglected Diseases Initiative,1998171.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments | Therapeutic trial design,2020 +C19439,222433/Z/21/Z,Interferon and Human Pandemic Viruses,"We wish to define the key interferon (IFN)-stimulated gene (ISG) effectors for three pathogenic human viruses - HIV-1, SARS-CoV-2 and influenza virus - and understand the molecular basis for antiviral function. Specific ISGs will be identified in unbiased gene silencing (siRNA/ CRISPRi) screens, some of which we have developed. For HIV-1, we will initially focus on the antiviral mechanisms and post-transcriptional regulation of post-entry inhibitors we have identified, human-TRIM5alpha and MX2, including the central roles played by ubiquitination and phosphorylation. Our discovery that NCOA7 suppresses endocytic virus infection (e.g., SARS-CoV-2) provides the opportunity to study how the endolysosomal system can be dysregulated, potentially through altering vacuolar-ATPase activity. New screens for ISGs targeting SARS-CoV-2 or influenza virus will be undertaken using wild-type viruses as well as engineered strains carrying disruptions in candidate IFN- or ISG-antagonists. We will explore the molecular mechanisms and regulatory pathways used by the most potent ISGs using multiple complementary experimental approaches, including proteomic and approved drug screens, and determine how these viruses escape or survive ISG action. By understanding the ISG effectors that can control these viruses, we will gain fresh insights into viral replication strategies, disease processes and host immunity, and inform future antiviral therapeutic development.",2021,2026,King's College London,2786488.12,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C19440,222426/Z/21/Z,Innate-like T cells and integration of host defence,"This research project aims to define the key roles of newly defined T cell subsets, and how they integrate signals between innate and adaptive immune responses to optimise host defence. Recent work on immune responses in human tissues has revealed the complex landscape of immunity and emphasised the role of poorly-defined unconventional T cell subsets. In the past 5 years my lab has defined some of these roles including 3 main findings - a striking sensitivity to innate cues, relevant for initiation of protective responses to viruses, a wide palette of functions including a role for barrier repair, and the ability to co-ordinate adaptive responses following experimental vaccination. In this application I aim to take these findings much further, harnessing a set of novel tools and aiming: 1) To define the mechanisms underpinning the link between MAIT cells (as a paradigm for innate-like T cells) and vaccine responsiveness; 2) To understand the mechanisms by which such cells may impact on outcomes of severe viral infection. Overall this work is highly relevant to major health challenges such as SARS-CoV-2, influenza, viral hepatitis and microbial infection - and to the vaccines needed to combat these challenges.",2021,2027,University of Oxford,2793408.99,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +C19441,222410/Z/21/Z,"IDDO: FAIR, equitable and sustainable data platform for infectious diseases","The COVID-19 pandemic has once again exposed the lack of coordination and cooperation across the research and development efforts of the infectious disease community. A key indicator of this failing is the lack of international, interoperable data platforms to provide rapid insight into disease pathogenesis and treatment. Access to data is an important tool for accelerating evidence, product development, and scientific innovation. Enhanced technology, infrastructure and systems for data platforms will increase Findability, Accessibility, Interoperability, and Reuse (FAIR), so that science can advance in a rapid, robust and innovative way, saving lives in the affected communities. Recognising the importance and complexity of the task at hand, this project brings together the vast experience of IDDO, Vivli, and other key stakeholders to deliver a broad, effective, and sustainable data platform(s) for infectious diseases. In this project, IDDO will: Enhance its platform for improved findability, discovery, and persistence which ensures that data are available in the long-term; Optimise and accelerate its data curation capacity; Streamline and accelerate its data access workflow; Develop a business plan to secure the sustainability and success of the platform",2021,2024,University of Oxford,6542967.71,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2021 +C19442,222407/Z/21/Z,Manufacture of a GMP SARS-CoV-2 challenge agent,"In the current COVID-19 emergency, a controlled SARS-COV-2 human infection model (CHIM) has the potential to accelerate the understanding of pathogenesis, induction of immunity and immune mechanisms of resistance to disease, as well as a means to test novel diagnostics and treatments, especially between waves of the pandemic, when occurrence of natural disease is relatively uncommon. A large number of SARS-COV-2 vaccine candidates are at various stages of development internationally including those which have recently entered mid-late stage clinical testing in field studies. In order to make the greatest public health impact, there is an urgent need to select the most promising vaccines in the shortest possible timeframe. In addition, human infection challenge can contribute to the identification of correlates and mechanisms of protection against infection and shedding of virus in vaccinated volunteers. Finally, the model may be useful in the determination of the durability of protection in seropositive individuals with documented prior wild type infection. This proposal is a dose titration study to generate two GMP challenge agents and establish the safety of a wild-type SARS-COV-2 controlled infection in the upper respiratory tract of young healthy volunteers that will allow swift and robust assessment of vaccine efficacy.",2021,2023,Imperial College London,5702173.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2021 +C19443,222389/Z/21/Z,Investigating the mechanisms of thromboinflammation induced by infection,"Thrombosis is estimated to contribute to 25% of deaths worldwide, yet our understanding of the mechanisms behind thrombus formation and related inflammation remain poor. This so-called thromboinflammation can occur as a result of severe infection, for example in sepsis and severe COVID-19. We aim to probe the lifecycle of the thrombus, and understand why it differs between different organs. To do this, we will use the well-established mouse models of Salmonella infection to study the composition of thrombi in different organs. We also aim to investigate the response of human platelets (the main component of many thrombi) to different strains of Salmonella, allowing identification of host and bacterial-specific factors that are affecting the thrombotic response after infection. This research will help further our understanding of the mechanisms behind the dysregulated inflammatory processes that occur upon infection, including during COVID-19, that can lead to fatal consequences.",2021,2023,University of Birmingham,0,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis,2020 +C19444,222377/Z/21/Z,The use of global connectivity estimates in real-time models of international infectious disease spread,"Human mobility plays an important part in the spread of infectious diseases. Mathematical models can assess the risk that an emerging outbreak will spread internationally, providing decision-makers with information to support early surveillance and control measures. In this project I will aim to improve how well these models capture international mobility patterns by exploring the suitability of different measures of connectivity. I will compare flight passenger data (which is commonly used in international infectious disease spread models) with alternative transport passenger statistics and novel data, such as location data from mobile phones. I will use these data sources (both individually and in combination) in models to make predictions of the risks of imported and exported disease cases, and assess how well these different models can retrospectively predict the global spread of COVID-19. I will use these findings to develop a statistical model and tools that are ready in advance of future outbreaks to make rapid assessments of the risks that they will spread geographically. The project will lead to more realistic models of international infectious disease spread and thus improve the information that is available to support decision-makers in controlling future outbreaks before they become widespread.",2021,2023,Imperial College London,0,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C19445,222374/Z/21/Z,Developing novel phylodynamic modelling methods for forecasting infectious disease outbreak detection and transmission dynamics,"Phylodynamic methods utilising genetic and epidemiological data, such as contact-tracing, hot-spot identification and modelling of strain-specific transmission dynamics, can provide a useful way for forecasting infectious disease outbreaks and transmission dynamics of interest. However, information from epidemiological investigations and genome sequences are rarely utilised together in current gold-standard methods used for outbreak assessment (2). We propose to develop novel phylodynamic methods for real-time outbreak detection of RNA-viruses (Sars-CovV-2, Influenza) using contact-tracing and predicted hotspot identification, as well as further developing understanding of transmission dynamics at the strain-specific level in a sustained outbreak over time. Sars-CoV-2 sequence data is sourced from COG-UK and linked to epidemiological patient data from PHE (3). Influenza sequence data is sourced from PHE, including strain-specific samples for Influenza A and B, and linked to epidemiological patient data from 2015 to present (4). Methods will be developed into publicly available R packages for application in future RNA-virus outbreaks. We aim to advance methods for incorporating genome sequence data into real-time forecasting of outbreak detection (5-8). Additionally, by increasing understanding of strain-specific transmission dynamics, we will advance understanding of seasonal infectious disease transmission at local, community and national level, and inform annual vaccine development in the UK (9).",2021,2023,Imperial College London,0,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies,Disease transmission dynamics,2020 +C19446,222346/Z/21/Z,Accelerating Access to Individual Participant-Level Data via the Vivli Platform,"Data repositories (such as IDDO and Vivli) have played a significant role in making research data available for secondary use. However, access to data needs to be further enhanced for accelerated innovations on infectious diseases by addressing the friction in data contribution, discoverability, access, and reuse. There is a strong alignment between Vivli the Wellcome's visions of improving the discovery and accessibility of Individual Participant Data related to COVID-19 in the short term, and for other infectious diseases in the long term. With this grant we seek direct support for discoverability and accessibility of data related to COVID-19, and to directly support Vivli to become an effective node in the ""FAIR Data Network"". The grant will focus on the following primary objectives: Recognition and credit for data contributions, Accelerated access to Individual Participant Data (IPD) hosted by Vivli, Discoverability of IDDO studies via the Vivli platform, and Discoverability of IPD hosted by Vivli and its platform partners (including IDDO) based on rich metadata).",2021,2024,Vivli (Centre for Global Clinical Research Data),1403852.72,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2021 +C19447,222303/Z/21/Z,Investigating how the presence of neutrophils in the lungs prior to infection with respiratory viruses can exacerbate disease severity in mice,"Respiratory viruses such as RSV, influenza viruses and the recently emerged SARS-CoV-2, represent a major global burden to public health. While infection with such viruses will often only result in mild ""cold-like"" symptoms, many will result in severe disease and require hospitalisation. Why some people get seriously ill while others only develop mild symptoms is not yet understood. Recent studies in both humans and mice have suggested that the presence of white blood cells, known as neutrophils, in the lungs prior to infection with respiratory virus results in more severe disease. The aim of this project is to investigate how the presence of these neutrophils alter the immune response to respiratory virus and ultimately how this drives more severe disease. To achieve our aims, we will use mouse models to characterise how and which parts of the immune environment in the lung that is changed by the presence of neutrophils prior to infection with respiratory virus and how this influence the severity of disease. This work will help us to better understand why some individuals are more at risk of severe disease following respiratory viral infection and help the development of effective treatments and vaccines.",2021,2023,Imperial College London,0,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Clinical characterisation and management,Disease pathogenesis,2020 +C19448,222217/Z/20/Z,Health Policy Watch Reporting on Covid-19,"Reliable, evidence-based media remains a key means of advancing public health literacy and bringing news, views and opinions from diverse regions of the world into the corridors of power. The vision driving Health Policy Watch, launched in 2019 as an open-access, non-profit health news service, is to create a new ""network paradigm"" that connects the dots between policy trends and realities in the global North and South. We provide coverage across 5 key themes, including: infectious diseases; non-communicable diseases; antimicrobial resistance; climate and environmental health; and health emergencies. The key objective of this proposal is to foster a more balanced- and ""solutions""-oriented approach to health policy dialogue around issues and choices that are critical to effective response to the COVID-19 pandemic - and to the broader global health agenda in light of COVID-19 realities. Institutional sustainability is a second key objective. To realize its public service mission, Health Policy Watch is committed to ensuring that all potential readers can access our content free of charge. As we work, with modest resources, to build a diverse array of donors and collaborations to advance that mission, Wellcome Trust support would empower us to develop a more sustainable and robust funding portfolio.",2020,2021,Global Policy Reporting,317378.43,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience",Communication,2020 +C19449,222199/Z/20/Z,"Mobilized, recruited, conscripted? Leveraging community health work, citizenship and public authority in northern Kenya","Who delivers health care, where and why? The COVID-19 pandemic has underscored stark global inequalities in answers to these questions. 'Community participation', an enduring pillar of interventions in the Global South, has been leveraged in response to COVID in Africa via Community Health Workers (CHWs). Key agencies who recruit Africa's army of Community Health Workers (CHWs) have declared them to be COVID's emerging 'first line of defence'. This research will examine the structural factors that lead to the recruitment of CHWs and which contribute to the persistent undervaluing of CHWs' work in Kenya. The research will innovate in its combination of discourse analysis, informed by critical/feminist/postcolonial thought, with detailed ethnographic fieldwork in Kenya's marginalized north. The research will firstly provide a critical reading of the 'imperial remains' within CHW recruitment practices on the part of health agencies and INGOs. The research will secondly provide a historicized reading of (gendered) narratives regarding citizenship, public service and voluntarism in postcolonial Kenya. This research will then be brought into dialogue with detailed interviews with and ethnography of/by CHWs in Isiolo, northern Kenya, with implications for CHW policy but also for rethinking the desirability and justness of one of global health's core assumptions.",2021,2026,University of Edinburgh,355053.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Africa | Europe,Gender,,,United Kingdom,United Kingdom | Kenya,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Health workforce,2021 +C19450,222165/Z/20/Z,BREATHE: Building Respiratory support in East Africa Through High flow versus low flow oxygen Evaluation,"With this funding, we hope to achieve a decrease in mortality for the 20 million critically ill adults in sub-Saharan Africa with acute hypoxemic respiratory failure. In the setting of COVID-19, governmental and nongovernmental organizations are working toward improving oxygen availability through large PSA plants and bedside oxygen concentrators. While sources of oxygen are increasing, what remains unknown is the impact of using different delivery systems for oxygen, which include low flow nasal cannula and facemasks, HFNC, CPAP, and invasive ventilation. Low flow systems are limited in the degree of oxygen support they can provide and are therefore only appropriate for mildly hypoxemic patients; non-invasive CPAP carries a significant aspiration risk for patients with altered mental status and requires close monitoring by trained staff; mechanical ventilation requires even more significant infrastructure, consumables, and human resources to operate safely. In HICs, HFNC has been shown to reduce the need for mechanical ventilation, and in some cases reduce mortality. In LICs, where safe mechanical ventilation is largely unavailable, we predict a robust mortality reduction. This funding will yield definitive evidence for HFNC's impact on mortality, and develop the resources to widely disseminate that evidence, including comprehensive strategies for implementation and scaling.",2021,2025,Beth Israel Deaconess Medical Centre,3601912.19,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2022 +C19451,222149/Z/20/Z,Health Security Activities of the Munich Security Conference 2020-2023,"Building on the expertise and support provided by the Wellcome Trust in recent years, the MSC wishes to create a direct continuation of existing work, sustainably strengthen its global health dimension and expand its reach with additional activities in response to COVID-19 and beyond. During the MSC fiscal year 2020-2021 activities will include two follow-up Digital Conversations and various roundtables and side events within the scope of the 2021 Munich Security Conference, a 2021 Health Security Roundtable in Berlin and potentially a Health Security Roundtable on the sidelines of the MSC Core Group Meeting 2021 in Washington D.C. Additionally, a Special Edition of the Munich Security Report, the ""Stability Report"" will address many current issues and challenges in global health security. As part of the grant proposal, the MSC will facilitate Wellcome Trust participation at the report launch and will give updates on report progress. Events similar in number and design will take place in the fiscal years 2021-2022 and 2022-2023. Due to COVID-19, detailed plans will only be made at a later stage. The MSC will keep the Wellcome Trust up to date on its plans for new MSC health security activities as soon as they become available.",2020,2023,Munich Security Conference,450437.95,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Germany,Germany,Health Systems Research,Health leadership and governance,2020 +C19452,222105/Z/20/Z,Epidemic Inteligence: Understanding how returning migrant waves drive epidemic seeding and community transmission events in the South Asian context to inform epidemic preparedness,"Nepal, as for much of Asia, has high levels of labour migration, particularly to neighbouring India and the Middle East. The SARS-CoV-2 pandemic has caused a chaotic mass return migration event. While the government has attempted to quarantine and test returning migrants the fragile infrastructure has been rapidly overwhelmed and repeated migration waves have occurred into remote rural areas. The epidemic in Nepal is now entering the rapid escalation phase. Despite this surge, the government has been forced to raise the lockdown, imposed since March 24th, due to the economic and political consequences. There is limited understanding of the pattern and extent of transmission in this context due to limited and sporadic testing. Understand how return migration is influencing the epidemic dynamics in rural vs. urban contexts. Understand how the reported data from the core government testing system compares to estimated community prevalence dynamics to predict testing capacity gaps and refine future response. Determine sensitivity and specificity of GeneXpert Xpress testing using nasopharageal swabs or saliva against RT-PCR for SARS CoV-2 infection. Sequence a cohort of 500 SARS CoV-2 samples to understand the patterns of repeated introduction, seeding and transmission occurring in rural and urban areas as the epidemic unfolds.",2021,2023,Liverpool School of Tropical Medicine,873061.53,Human Populations,Asian,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2021 +C19453,222097/Z/20/Z,The OpenSafely Research Platform,"OpenSAFELY is a new secure analytics platform for electronic health records in the NHS, created to deliver urgent results during the global COVID-19 emergency. It is now successfully delivering analyses across more than 24 million patients' full pseudonymised primary care NHS records, with more to follow shortly. All our analytic software is open for security review, scientific review, and re-use. OpenSAFELY uses a new model for enhanced security and timely access to data: we don't transport large volumes of potentially disclosive pseudonymised patient data outside of the secure environments managed by the electronic health record software company; instead, trusted analysts can run large scale computation across live pseudonymised patient records inside the data centre of the electronic health records software company. This pragmatic and secure approach has allowed us to deliver our first analyses in just five weeks from project start.",2020,2023,University of Oxford,3002509.66,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research,Health information systems,2020 +C19454,222057/Z/20/Z,Outbreak Science Rapid PREreview - COVID-19 response,"The coronavirus pandemic has led to an unprecedented uptake of preprints, with researchers from all over the globe collaborating and sharing information at record speeds. The Wellcome Trust-funded open source platform Outbreak Science Rapid PREreview (https://outbreaksci.prereview.org) launched by our team on January 1, 2020, is well-positioned to help provide rapid feedback and a help filter the high number of COVID-19 preprints for quality and potential impact. In just a few months, the platform has reached about 500 users, 80 rapid reviews, and more than 230 requests for reviews, the majority of which are for COVID-19-related preprints. These numbers grow every day, and so do opportunities for collaborations with third-party sites and efforts that can increase the discoverability of the content and accessibility to the tool. To leverage our platform and aid in tackling this pandemic, our team asks for financial support for the following activities and positions: Feature implementation and customization of our open API to make COVID-19-related content more discoverable via integration with third-party sites, such as preprint servers and research platforms; A full-time project manager to lead and coordinate the work.",2020,2021,Code for Science and Society,42741.21,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,Data Management and Data Sharing,,,United States of America,United States of America,Health Systems Research,Health information systems,2020 +C19455,222048/Z/20/Z,Enabling ISARIC Clinical Characterisation Protocol (CCP) roll out in LMICs,"By bringing GOARN Research and ISARIC partners together in the LMIC setting during COVID-19 we hope to strengthen the clinical, social science and operational research response. Aim: to support the roll out of the ISARIC WHO natural history protocol (known as the Clinical Characterisation Protocol - CCP) across LMICs: Overarching goals: Support the roll out/uptake of the CCP across 5 countries per region, where feasible* (across four ISARIC regions of S America, Africa, S Asia & SE Asia). Support the set up and running of local dynamic clinical data dashboards in at least 10 sites per ISARIC region Share the aggregate data with WHO to assist with providing a global picture on the incidence and presentation of moderate to severe cases across a representation of the LMICs to inform clinical management and public health planning and control. Support the establishment of follow up modules and programmes for discharged hospitalised cases in 5 sites per region to evaluate longer term health impacts of COVID-19 on individual, health services and society to inform prevention and care planning. *Brazil are in an intense first wave and reaching out to another 4 S. American countries would be challenging at the time of writing.",2021,2022,University of Oxford,464688.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Health Systems Research | Research on Capacity Strengthening,Health information systems | Cross-cutting,2021 +C19456,222047/Z/20/Z,UNITE Global Summit: Virtual 2020,"The Wellcome Trust Fund and UNITE collaborate to build the capacity of parliamentarians to advocate for the elimination of infectious diseases in their countries and around the world. Collaborations include activities designed to strengthen the exchange of evidence-based knowledge through dialogue and information sharing on infectious diseases, legislative processes and policymaking. The UNITE Global Summit: Virtual 2020 will convene online on 7-8 September 2020. This event will bring together members of parliament from around the world in order to commit, inspire and empower policy makers towards the achievement of the UN Sustainable Development Goals over the next decade. Participants will work to develop a roadmap of clear policy actions to eliminate the threats posed by communicable diseases. This alignment of a common vision will culminate in the signing of UNITE's 2020 Declaration. Wellcome Trust will play a key role in Panel Session 1: Epidemics - What are we learning from the global response to COVID-19, by co-sponsoring the UNITE Global Summit: Virtual 2020 with the Coalition for Epidemic Preparedness and Innovations (CEPI).",2020,2020,UNITE - Association of Parliamentarians to End Infectious Diseases,2969.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,Portugal,Portugal,"Policies for public health, disease control & community resilience | Health Systems Research | Research on Capacity Strengthening",Policy research and interventions | Health leadership and governance | Systemic/environmental components of capacity strengthening,2020 +C19457,222042/Z/20/Z,afrimapr R building-blocks for the operational COVID-19 health response,"We will develop software building-blocks to facilitate the use of operational health data in Africa to aid the COVID-19 response. The main gap the new work addresses is the use and re-use of health data in the immediate operational response to COVID-19. The project will run under the umbrella of afrimapr, an existing Wellcome Open Research Fund project improving the use of health research data. The project philosophy is the same: firstly to develop open-source R components to assist African data scientists in creating tools to address local issues, secondly to develop training resources and thirdly to promote them within African data communities. We have already started assessing, and improving access to, open-data on African health facility locations. This extension will allow us to continue working with new collaborators; healthsites.io and OpenStreetMap communities that collate and crowdsource health facility data. We will reach out to African data communities through DFID advisers to African ministries, national statistics institutes through the Global Statistical Service, and our networks and social media. Components for working with African health zones will also be developed. Increasing the use of open-access health data has the co-benefit of incentivizing improvements to the availability of the data themselves.",2020,2021,Liverpool School of Tropical Medicine,65792.12,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Community engagement | Institutional level capacity strengthening,2020 +C19458,222037/Z/20/Z,Cross Cutting Social Science Research for COVID-19,"The global community has mobilised in an unprecedented way to deliver research in response to the threat of COVID-19. In February 2020, priority areas for research were advanced under a coordinated mechanism convened by the World Health Organisation. For social science a cross cutting research agenda was proposed in recognition of the vital role played by individuals, communities and populations worldwide in slowing disease tranmssison and providing care for COVID-19 and beyond. Research initiatives, including over 300 social science studies funded by GloPID-R members alone, have been advanced against these social science priorities. Building on earlier successes in supporting epidemic-relevant research, the research arm of GOARN, the Global Outbreak Alert and Response Network, has actively coordinated this work with WHO. There is a pressing need to properly resource coordination and knowledge mobilisation of epidemic-relevant social science research. Further, there is an important opportunity to leverage the reach and expertise of GOARN and establish infrastructure for the COVID-19 response as well as for future scenarios to ensure that structures for epidemic-relevant research can take hold: the well worn phrase of building the ship while we sail it is unsustainable as an effective and efficient research response to infectious disease epidemics.",2021,2022,University of Oxford,457209.23,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C19459,221986/Z/20/Z,Sabin-Aspen September Convening on sustainable vaccine ecosystem,"The COVID-19 pandemic underscores the urgency and importance of vaccines and immunization to global health. There are significant and pressing scientific, technical and policy solutions needed to tackle the enormous challenges we face in a world with COVID-19. Bold thinking across disciplines, actionable recommendations and strong advocacy are all urgently needed to advance innovative ideas, overcome these hurdles and inform future programmatic work, in particular in light of the COVID pandemic. The goal of this project is to virtually convene The Sabin-Aspen Vaccine Science & Policy Group (Vaccine Group) in September 2020 to explore how the effort to accelerate the development of COVID-19 vaccines through ACT Accelerator and other initiatives can be harnessed to bring about a ""new normal"" for vaccine/vaccination ecosystem and ensure that vaccines for diseases with epidemic potential or those affecting low income populations are developed. The Sabin Vaccine Institute and the Aspen Institute, co-conveners of the Vaccine Group, will draft and disseminate a meeting report on the convening with principal findings and recommendations to inform program and policy planning.",2020,2021,Albert B. Sabin Vaccine Institute Inc,184826.5,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,Health Systems Research,"Medicines, vaccines & other technologies",2020 +C19460,221914/Z/20/Z,Molecular regulators of the alarmin IL-33 in health and disease,"IL-33 is a critical cytokine in allergy, obesity, helminth infection, sepsis, and respiratory viral infection. Blockade of IL-33 (or its receptor, ST2) is currently being trialled in a range of allergic and inflammatory conditions, including Covid-19. The cytokine has a short half-life on release, but conversely has effects at distal sites and over long periods. Furthermore, innate immune cells in the intestine are poorly responsive to IL-33, but susceptibility to intestinal helminths is strongly controlled by IL-33. This project will investigate: 1) How, at a protein structural level, parasite proteins effectively block IL-33 responses. Determination of the effects on the parasite and host of blocking parasite modulation of the IL-33 pathway. 2) What are the roles and targets of IL-33 released from the intestinal epithelium, both locally (in parasite infection) and systemically (in diet-induced obesity). 3) The role of soluble IL-33 receptor in stabilisation of IL-33, and its effects at distal sites. To achieve these aims will we will use structural biology, in vivo models of IL-33-dependent responses, creation of cell-specific ST2-deficient mouse strains, and generation of a soluble ST2-deficient mouse. Finally we will use human blood samples and three-dimensional culture methods to ensure translation of these findings to humans.",2020,2026,University of Dundee,2210836.21,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Disease pathogenesis,2021 +C19461,221841/Z/20/Z,Dis-Ease,"Declaring ""war on disease"" affects how we treat sick people, how we define the ""public"" in public health, and how we respond to real-world pandemics.. This was demonstrated vividly during the COVID-19 crisis, when these declarations of war initiated militarized states of emergency, prompted border lockdowns, and refreshed old fears about ""foreign"" pathogens. But why was this public health crisis being treated as a national security issue? What else does this metaphor do in the world? And what if it weren't a war? To answer those questions, the feature-length documentary ""Dis-Ease"" retraces the origin and evolution of our ""war on disease"" through the history, philosophy, culture, and pop-cultural imaginaries of medicine. It is constructed around particular episodes in the history of human encounters with epidemic, endemic, and pandemic diseases, including plague, malaria, cholera, tuberculosis, influenza, HIV/AIDS, and COVID-19. By examining the cultural history that runs alongside the growing scientific understanding of these diseases over time, DIS-EASE looks to understand how pandemic preparedness became framed as biodefense, and how that has contributed to the present crisis. And it proposes alternatives for the future.",2020,2022,Indexical Films LLC,60269.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +C19462,221818/Z/20/Z,"Structure, mechanism and dynamics of recoding in viral infection","Many RNA viruses (e.g. SARS-CoV-2, HIV-1) have evolved ways of reprogramming translation to expand the coding capacity of their small genomes. 'Recoding' events such as -1 frameshifting, stop codon read-through and StopGo peptide release are necessary for viral replication, producing viral proteins in optimal ratios for efficient assembly. Recoding is regulated by a complex interplay between the elongating ribosome, cis-acting elements in the mRNA or nascent peptide, and trans-acting protein factors. Elucidating the structural basis of recoding is essential to understand viral pathogenesis. However, classical biochemical approaches cannot accurately capture kinetics or per-ribosome heterogeneity, making it difficult to define a window of opportunity for structure determination. Recent technological advances allow single-molecule fluorescent imaging of translation in real-time. I will apply these methods to study recoding in vitro and in live cells, starting with -1 frameshifting in SARS-CoV-2, HIV-1 and EMCV, which utilise topologically-distinct stimulatory elements. I will determine the structure of key ribosomal states by time-resolved cryo-EM, and investigate the structure and stability of stimulatory elements using crystallography, single molecule FRET and optical tweezers. Longer-term, this approach will be applied to investigate other recoding events, thus revealing universal and case-specific mechanistic principles, and highlighting new avenues for therapeutic intervention.",2020,2026,University of York,1756957.75,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C19463,221795/Z/20/Z,Targeting membrane proteins in their native environments - Mass spectrometry meets cell biology,"The overarching goal of my research is to understand the relationship between membrane proteins and their lipid surroundings. This is important since many membrane proteins are unable to retain their structure and function when extracted from their native environment and reconstituted into a membrane mimetic. Dynamic proteins, for example G-protein coupled receptors, solute carriers and sigma receptors, are intimately connected to their membrane environments and prone to loss of function and activity in detergent micelles. To overcome this disconnect we will develop and apply our mass spectrometry approaches to examine dynamic drug targets within their membrane context. Our key goals will be to challenge these receptors and transporters with agonists, antagonists, inhibitors and lipids effectively in situ. Examples include solute carriers which during tumour progression respond to the need for an altered metabolism by increasing expression. Analogous methods will be used to uncover the targets of mitochondrial and lysosomal therapies. Many of our research themes converge on consequences of the COVID-19 pandemic. While this remains an area of intense scientific scrutiny we will focus on the less-studied receptors and 'infection enhancers', and contribute to understanding the roles of lipids in the endocytosis and viral recognition pathways.",2020,2026,University of Oxford,2911296.37,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19464,221790/Z/20/Z,Children and Young People's Participatory Research and Communication for Change,"Aligned with Wellcome's commitment to leveraging public partnership - throughout the cycles of response, recovery and resilience/sustainable preparedness - to inform research, create trusted research, and increase the access and use of research more equitably across communities, this project will (1) Fill a current gap in children and young people (CYP) insights around Covid-19 and other issues of health and science related research, (2) Equip young people with participatory research and multi-media production skills, and (3) Develop a scaleable participatory model of research and communication for change. To achieve this, UNICEF C4D, a leader in using communication strategies to empower CYP as critical actors in research and development, will partner with innovative multi-media platforms -- inclusive of video, community radio, and mobile-based platforms -- to facilitate CYP-led cross-country surveying, personal stories (via video), in-depth interviews (with/by CYP), and deliberative dialogues (via community radio, video and mobile-based platforms), that will uncover CYP needs, behaviours and experiences with COVID-19 and other priority health and science challenges. UNICEF and its partners will develop a replicable model and partnership base for CYP-led research and engagement to influence social and behaviour change to support future joint research engagement to inform policy and programmatic decision making.",2020,2022,UNICEF UK,315133.2,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,International,Europe,,,,International,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +C19466,221680/Z/20/Z,Genomic epidemiology of acute respiratory distress syndrome and fibrosis in patients with COVID-19,"COVID-19 is an infectious respiratory disease with a global devastating health impact. Genetic and environmental factors influence COVID-19 susceptibility and outcomes, including the development of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. These lung pathologies have a high mortality and there are no specific treatment options or effective prognostic methods for patients. Therefore, there is an urgent need to identify effective biomarkers of disease prognosis. The aim of this research is to perform a genomic epidemiology study of ARDS and pulmonary fibrosis in patients with COVID-19. For that purpose, we will perform genetic overlap studies that will include genetic correlation analyses, polygenic risk score approaches, and assessments of overlap of individual genetic variants, followed by fine mapping studies, bioinformatic approaches to identify the likely causal genes, and further experiments to evaluate their role in disease and their potential as drug targets. Results of these analyses will allow us to identify novel genetic risk factors and to develop risk prediction models, which could enhance COVID-19 patient stratification for those at increased risk of lung sequela. Furthermore, the project will reveal novel therapeutic strategies, which would translate into improved and more personalised clinical care for patients at risk of lung fibrosis.",2020,2025,University of Leicester,394890,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2021 +C19467,221579/Z/20/Z,"Understanding the impact of COVID-19 on bacterial sepsis, antibiotic consumption and stewardship, and antimicrobial resistance","This study aims to address the following questions through a global network of hospitals: Is there evidence for a reduction in the total number or rates (per 1,000 inpatients) of blood cultures taken over twelve months? Has there been changes in antimicrobial usage (quantitative and qualitative)? Are there major changes in antibiotic resistance profiles from major pathogens? Have there been changes in antimicrobial stewardship and why? What is the overall change in the management of these patients? What is the impact of COVID-19 on infection control practices during the pandemic? Is there any evidence of reduction in nosocomial infections and bacterial outbreaks during the COVID-19 pandemic? We will collect clinical (patient-based [severe pneumonia, ARDS, sepsis patients], hospital and microbiological data from 11 countries (UK, Switzerland, Italy, Brazil, Nigeria, Malawi, Turkey, Iran, India, Bangladesh and South Korea). Our primary outcome will be to determine if there has been a reduction in blood cultures taken. Secondary outcomes include whether 1. changes in antimicrobial usage 2. major changes in antibiotic resistance profiles from major pathogens in hospitals during COVID-19 and correlate resistance profiles with antibiotic usage. 3. changes in infection control practices and other aspects of sepsis management behaviour during the COVID-19 pandemic.",2020,2023,University of Oxford,1008949.11,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Africa | Americas | Eastern Mediterranean | Europe | South-East Asia | Western Pacific,,,,United Kingdom,United Kingdom | Switzerland | Italy | Brazil | Nigeria | Malawi | Turkey | Iran | India | Bangladesh | South Korea,Clinical characterisation and management | Health Systems Research | Infection prevention and control,"Supportive care, processes of care and management | Health service delivery | IPC in health care settings",2021 +C19468,221574/Z/20/Z,Wellcome Longitudinal Population Study COVID-19 Steering Group and Secretariat,"Our objective is to provide an efficient coordinating body (""secretariat"") for the continued development, deployment, collection and analysis of a shared COVID-19 questionnaire across UK cohorts. The value of undertaking this in multiple longitudinal UK cohorts is that data can be collected in extremely well characterised members of the population across a wide demographic range who are already engaged in research, who have had data and biological samples collected on them, who have an established collection of record linked data already record linked and who sit behind supported infrastructure able to undertake novel data collection and research. Each of these cohorts is research active and collectively offers a depth or domain expertise not available within any one cohort, including that of UK Biobank. In this first coordination of COVID-19 research in deeply characterised UK cohorts, we identified the added value of a core questionnaire prospectively aligned to capture data pertinent to understanding COVID-19, as well as the direct and indirect consequences of the pandemic on health, wellbeing, social and economic outcomes.",2020,2021,University of Bristol,158979.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19469,221566/Z/20/Z,A Unit for Health Evidence and Policy in Laos,"There is a need to build capacity and improve evidence-informed decision-making concerning resource allocation and priority-setting in health in low- and middle-income countries, such as Laos. This kind of capacity building and institutional strengthening is all the more important in an era of aid transitions and uncertainty related to the current COVID-19 pandemic, to enable Laos to continue progressing towards Universal Health Coverage. We propose the creation of a Unit for Health Evidence and Policy (UHEP) based in the University of Health Sciences in Vientiane, to enhance the use of research evidence to inform policy. UHEP will focus on health technology assessment (HTA) as a tool to enable priority-setting. We aim to complete four main activities for this pilot project over one year. Situational analysis of the Lao health policy context including stakeholder mapping Training of Lao researchers and policy makers in HTA and on synthesis and use of research evidence (includes funding for one MSc student) Development of a roadmap for institutionalisation of rational priority setting in health policy development in Laos Selection and implementation of a pilot HTA project At the end of this year UHEP will be established as a government technical partner for HTA in Laos",2020,2022,University of Oxford,65920,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,South-East Asia,,,,United Kingdom,Lao People's Democratic Republic,Research on Capacity Strengthening,Cross-cutting,2020 +C19470,221553/Z/20/Z,The benefits of decarbonised electricity generation in cities,"While prior national level and regional studies have evaluated the contribution of coal combustion on air quality-related health impacts at the national or regional level, a concrete understanding of how coal combustion impacts urban populations can make a strong case for the rapid phase-out of coal-fired electricity generation in cities around the world. Project aims: (1) demonstrate a strong urban case for a rapid-phase out of coal-fired electricity generation; and (2) utilise the research results for an effective advocacy and communications campaign at COP26. In the research project, C40 will estimate the contribution of coal combustion for C40 city electricity generation to global GHG emissions, to air quality-related health burdens in C40 cities, to COVID-19-related health impacts as well as analyse the economic benefits of different coal phase-out scenarios by looking at: (1) the economic value of improved health associated with reduced coal combustion for electricity generation in C40 cities; and (2) the number of net jobs that are generated with a switch from coal combustion to clean energy.",2020,2022,C40 Cities,308046.8,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19471,221465/Z/20/Z,A pilot study of a culturally appropriate hospital-based pulmonary rehabilitation programme among adults with functionally limiting chronic respiratory diseases in Malawi,"Malawi suffers a substantial burden of chronic respiratory diseases (CRDs) which causes significant morbidity and loss of economic productivity, and affects patients, families and health systems alike. CRDs are a major risk factor for Coronavirus Disease 2019 (COVID-19). Pharmacotherapy for CRDs is of limited benefit and costly. Its rational use could be complemented by non-pharmacologic treatments. For chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) is well established as highly effective intervention which improves symptoms, quality of life and survival. PR is comprehensive package of interventions including exercise training. PR is now sufficiently understood to obviate further randomized trials in High Income Countries (HICs). However, given the design and delivery of programmes should be adapted to patient groups and context, high-quality data are needed outside HICs. My pilot study will determine feasibility and acceptability of PR in Malawi. Specifically, I will: (1) co-design, with service users and stakeholders, a locally appropriate PR program for patients with functionally limiting CRDs in Malawi, (2) examine lung function, exercise capacity and health status of participants before and after their participation in a PR program, and (3) examine participants' levels of attendance, participation and adherence to the programme. Keywords: chronic respiratory diseases, pulmonary rehabilitation, Malawi",2020,2023,Liverpool School of Tropical Medicine,73620,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Unspecified,,,,,,,,,Other,Wellcome Trust,United Kingdom,Europe,Africa,Africa,,,,Malawi,Malawi,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +C19472,221455/Z/20/Z,"Ethics, youth mental health, and infectious disease outbreaks","To control the spread of the 2019 coronavirus disease (COVID-19) outbreak governments around the world have introduced public health measures including social distancing, isolation, and quarantine. This has created conflicts between competing ethical values, particularly protecting the publics' health and safety v. respecting individuals' liberty and preferences. Concerns have been raised about the impact of currently-implemented measures on people's mental health. Children and young people may be affected in unique ways, due to their younger age and specific role in society. Yet, their mental health needs may be easily overlooked when professional care is devoted to those who are in most immediate need, i.e. the immunocompromised and the elderly. The aim of this project is to conduct a systematic review of the evidence on the impact of social distancing, isolation, and quarantine on young people's mental health and wellbeing, and to interpret it in light of the ethics literature on public health emergencies. This work will be used to develop a UNICEF working paper focused on ethically-robust policy recommendations, so that public health measures that will be implemented in future infectious disease outbreaks are mindful of children's mental health needs. Children, young people, COVID-19, mental health, ethics, UNICEF, systematic review",2020,2021,University of Oxford,20138.75,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts,2020 +C19473,221389/Z/20/Z,Empowering Technology? Issues of Access in Digital Primary Care,"In 2019, the NHS Long Term Plan and GP Contract committed doctors to making online their default patient access point by 2023. The widely used NHS app and web-based appointment and repeat prescription systems will be updated to facilitate, e.g. video consultation and remote monitoring. England's provider, NHS Digital, claims these changes will increase capacity and cut costs by reducing physical attendance. Many consumer champions and academic experts have questioned the lack of independent evaluations of the technology, and stress the likelihood that privileging digital access will exacerbate existing healthcare inequalities. The expedited roll-out of these technologies required by the current COVID-19 crisis may heighten such concerns by evidencing a 'digital divide'. A rapid review will bring together current research from academia, the public sector, industry, and third sector. This will demonstrate the current state of digitisation and each group's specific concerns and interests in implementation. Interviews will then concentrate on areas of consensus surrounding best practice, establishing several case studies of leadership. For policymakers, it will set out possible solutions for avoiding the exclusion of patients from specific age, income, or ethnic backgrounds; and draw attention to the possibilities for partnership by highlighting shared interests across stakeholding groups.",2020,2021,University of Warwick,9355.88,Human Populations | Other,Unspecified,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,Digital Health,,,United Kingdom,United Kingdom,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health service delivery,2021 +C19474,211080/Z/18/A,Dissecting the role of aryl hydrocarbon receptor in thermogenic adipose tissue,"The ongoing COVID-19 pandemic has changed our world and lives, in many different ways. Restrictions on social contacts and closure of schools have brought with them a significant disruption to children's daily routines, including exercise patterns and eating habits. The anxiety associated with social isolation, in combination with an increased sedentary lifestyle, has led to serious concerns about the long-term impact of COVID-19 on the global childhood obesity crisis. Our interactive science workshop ""You've got guts!"" will focus on positive messages centred around what keeps us healthy and why our guts play a central role in promoting health. Our workshop is a stimulating virtual as well as real-life learning experience designed for pupils aged 8-11 in our local community (White City). In collaboration with experts in science communication and professional science animators we will create several animated features conveying key aspects of gut health and healthy diets. The animated features, combined with direct two-way dialogue between pupils and scientists, will help pupils gain a better understanding of the connection between diet, gut health and overall well-being. Workshops will be virtual initially, but, as current lockdown restriction are eased, will be disseminated more widely as part of local science festivals and events in dedicated engagement spaces. Scientists involved in this project will gain valuable training and experience in PE with young audiences. Our PE activities will help develop and deepen links between our Institute and local schools, strengthening our Institution's reputation and visibility in the local community.",2021,2023,Imperial College London,97607.4,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19475,206444/Z/17/B,Use of the cytoskeleton to control Shigella infection,"COVID-19 has helped to illuminate the fundamental importance of young people and scientists effectively communicating the urgency of infectious disease. This project will develop the ways in which our science explains and communicates discoveries to a wider audience, using story and narrative devices familiarly used in animation and graphic novels as gateways to complex ideas. The body of work created will be a snapshot of where Mostowy lab research is in 2020, and a tool to develop the way in which the lab communicates its research. The project will be made with members of the Mostowy lab, with input from students and young people in London and Manchester, collaboratively producing an animated film examining central research concerns of the Mostowy lab including; Shigella, superbugs, antimicrobial resistance in a post-antibiotic environment, and the global health challenge these present. Inclusive sharing events will bring together the professional film we make with the creative work made by young people, giving an opportunity for us to discuss and appraise the learning from each experience. The work will be shared, at different stages of its development, at public events in London and Manchester, online, and at festivals internationally. Developing from the award-winning Wellcome Trust funded animation Loop (2016), this new project will be a legacy tool to explain the lab's most recent discoveries to a non-scientific audience, as well as to any researcher, healthcare professional or stakeholder. It will include ideas from young people as well as researchers, creating engaging visuals about compelling material.",2020,2023,London School of Hygiene & Tropical Medicine,115693.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Other secondary impacts,2020 +C19476,203109/Z/16/B,Wellcome Centre for Cultures and Environments of Health,"During the Centre's first three years, we have focused on establishing transformative research and engagement programmes, developing partnerships with policy-makers and creative organisations, building an open research culture, and recruiting doctoral students, early career researchers, and senior staff. Committed to engaged research that enables health and well-being, our projects have brought researchers, public partners, and health organisations together to address key health challenges, including: the health impacts of loneliness and social isolation; the value of different forms of evidence in health policy; the impact of relationships on children's health; and community access to - and involvement in - research and data governance. Additional funding will allow us to address further the health impacts of social and environmental inequalities, specifically through projects on health across the life course, ageing and dying, co-creating healthy cities, and recovering from - or living with - the social and cultural impacts of COVID-19. These research programmes - as well as an innovative Masters course in transformative health research and practice - will enable us to fully embed engagement and impact in our work locally, nationally and internationally, build training and career pathways in transdisciplinary research, and strengthen our commitment to an inclusive research culture.",2020,2022,University of Exeter,1823798.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C19477,202471/Z/16/A,Probing the molecular basis of translation-replication switching in pathogenic RNA viruses,"Viruses that use a single strand of positive sense RNA (+ssRNA) as their genomes number a breadth of human pathogens including Zika virus (flavivirus), poliovirus (picornavirus), norovirus (calicivirus) and SARS-CoV2 (coronavirus). A number of key, fundamental questions regarding how these viruses regulate usage of their genomes remain. Answering these questions not only provides new biological insights into host-pathogen interactions but could prove critical in identifying new strategies for control. These viruses use the same molecule of RNA for protein expression and as a template for replication. However, these processes occur in opposing directions i.e. translation in a 5′-3′ direction and replication in a 3′-5′ direction. This therefore necessitates a ""lifestyle switch"" for any single RNA molecule in a cell, the details of which are unknown. We will use a multidisciplinary approach including in vitro reconstitution, cell biology and infection studies to determine how lifestyle switching of genome usage is regulated during infection by +ssRNA viruses. This work will lead to a new paradigm in our understanding of the evolution of genome organisation and function in an important class of pathogenic viruses.",2021,2025,The Pirbright Institute,874550.2,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +C19478,110146/Z/15/B,"New perspectives for anti-viral therapy: The regulatory roles of genomic RNA in virus assembly, infection and evolution","The Covid-19 pandemic has generated widespread interest in viruses. This public engagement initiative is an opportunity for members of the general public to explore the science underpinning viruses and showcase the opportunities for antiviral therapy generated by Wellcome Trust funded research. Viano - a fusion of the words ""virus"" and ""piano"" - is a virtual instrument for playing viral genome data-generated music in concert with 3D virus visuals. Its aim is to communicate the concepts of mutation and selective pressures in viral evolution, the challenges they pose for antiviral intervention, and the opportunities for therapy arising from our discovery of genetically robust features in viral genomes. Viano will be offered as a gallery exhibit and for home use as an app. In the Lowry Museum gallery, Viano will work on a large scale: the main virus 3D image will be projected on the wall (7m x 7m) and users will have access to a large projected musical keyboard on the floor with over 29,000 keys representing the virus' genomic sequence. Both image and keyboard will be operated via body movement in a Covid secure manner, and a musical genome keyboard on the screen will also be accessible via an Android/Apple mobile and tablet app. Viano will come with a full programme of workshops and debates and will give the public the ability to save and share their musical viral compositions online.",2020,2022,University of York,82996.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Community engagement,2021 +C19479,109356/Z/15/D,The evolutionary and mechanistic basis of pathogen host shifts,"A major source of emerging infectious disease are virus host shifts, where a pathogen jumps into a new host species (e.g. HIV, Ebola, SARS-CoV-2). Research to date has focused on the role of host genetics. Here I will examine the role pathogen genetics (relatedness) and ecology (interactions between microbes) play in emerging infectious diseases, which will be critical to predict future host shifts. The first goal is to understand how patterns of susceptibility correlate amongst different pathogen taxa. I will infect hosts with different viruses and other pathogens to test the importance of the host phylogeny in determining susceptibility for each pathogen. For example, if a host is susceptible to one virus, are they also susceptible to other types of virus, or is susceptibility pathogen specific? This is critical for understanding whether the characteristics of an emerging pathogen can be predicted based on our knowledge of other related pathogens. Next, I will investigate how interactions between microbes can alter the likelihood of pathogen emergence. I will examine whether the outcomes of co-infection and microbiome-pathogen interactions are the same or different across host species. This has important consequences for understanding how biotic interactions could alter the outcomes of pathogen host shifts.",2021,2025,University of Exeter,995148.77,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2022 +C19493,,"Production of Molecular Based Point-of-care Protocol for SARSCoV-2 Detection among Humans, and Comprehensive Atlas of Possible Coronavirus Immune Response Differences Between Humans, and Non-Human Primates.","A: Background: Covid-19 has spread to almost all countries of the world and caused massive losses both in health and economic viewpoints. Apart from humans, scientific evidence also shows that primates are very sensitive to human diseases. Mountain gorillas for instance are prone to some respiratory illnesses that afflict humans. A common cold can kill a gorilla. In Rwanda, where tourism is an important source of revenue, and the government has prioritized the protection gorillas during COVID-19 with restrictive measures, there is no scientific evidence available about any potential transmission of COVID-19 from humans to gorillas or vice-versa. In addition, the adequacy of immunological defense mechanism in gorillas has not been tested yet. Some scientific experts are indicating that primates, including mountain gorillas, are likely susceptible to complications arising from the COVID-19. Today, more than 600 mountain gorillas live in Virunga massif where Volcanoes National Park is located. Not only many primate populations are already endangered, but also a spread of COVID-19 could put them in even more danger. B. Goal and Objectives The main goal of this study is twofold; first, to produce a Comprehensive Atlas of Possible Coronavirus Immune Response Differences Between Humans, and Non-Human Primates; second, in collaboration with our partners, to produce a molecular-based point-of-care protocol for SARS-CoV-2 detection. Objective 1: The Humans' sample (from recovered, active, and naive), as well as non-human primates samples (from chimpanzees, mountain gorillas, baboons, golden monkey, African green monkeys) testing regime includes: • To assess the production of neutralizing antibodies among different groups of humans and nonhuman primates, • To stimulate the T cells and assess their activities (activation markers expression, production of cytokines); • To document a scientific proof of respiratory infections among the non-human primates' routes of transmission; • A possible functional comparison of SARS-CoV-2 immune responses pathways (susceptibility, protective immunity) between humans, and non-human primates; • Possible epidemiology of SARS-CoV-2 in different selected non-human primates' reservoirs. 9 Objective 2: The detection protocol includes the following: • A point-of-care (hardware) instrument that is fit for purpose. • A biological assay that includes a simple extraction (heat and chill) protocol and fluorescent-dye based detection of Covid-19. • A software capable of depositing the test results into a central database from distant geographies where the assay is performed into a secure central database. i) The first stage involves testing primers/probes against a synthesized and/or cloned virus target into a vector. ii) The second stage will include testing of deactivated viral titres from a Guthrie card. The main reason for this kind of testing stage is to control and optimize the nucleotide extraction method before the isothermal PCR detection protocol. iii) The third and final test run will be testing clinical samples for both the extraction method and isothermal PCR detection to assess the functionality of the assay within various matrices applicable for SARS-CoV-2 testing. D: Expected Outcomes are: • A comprehensive atlas of possible SARS-CoV-2 immune response differences between humans, and non-human primates; • A thorough assessment of mountain gorilla's susceptibility to SARS-CoV-2; • A protocol for recommendation for preventing nonhuman primates given the current covid-19 outbreak; • A T16 LAMP instrument capable of conducting Covid-19 assays at point-of-care; • A LAMP based functional assay that can detect SARS-CoV-2; A B C D A: Mountain gorilla physical Examination; B: Sampling; C-D: RNA extraction process of nonhuman primates' samples at Wildlife Virology laboratory- Rubirizi, Kigali Methods: Isolated strains will be sequenced using the Next Generation Sequencing. Obtained sequences will be analyzed and compared to several other strains identified in other places. Amplicons will be prepared for sequencing. The detection protocol will include the use of a molecular diagnostic approach for COVID-19 diagnosis using realtime loop-mediated isothermal amplification (RT-LAMP). Here there will be three sets of virus and virus ""equivalents"" testing. 10 • An IT system based on a web application that can transmit test results from the field to a central database.",2021,-99,Rwanda Biomedical Center,60260.45,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Americas | Europe,,,,Rwanda,Rwanda | South Africa | Finland | Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Immunity | Animal source and routes of transmission, +C19494,,Development of on-site rapid diagnostic test for early detection of COVID-19 based on CRISPRCas and Surface-Enhanced Raman Spectroscopy,"A: Background During unpredicted epidemic outbreaks such as COVID-19, establishment of early-stage diagnostic tools, which can favor timely diagnosis, and control the spread of the disease in order to sustain and monitor people's lives are always a priority in personalized medicine. Most employed tools such as real-time PCR (Polymerase chain reaction) and ELISA (Enzyme linked immunosorbent assay)-based techniques are still expensive, tedious and their sensitivity is of concern. CRISPR/Cas systems (clustered regularly interspaced short palindromic repeats)/ associated Cas proteins), hold promise in the development of novel and reliable diagnostic tools. CRISPR/Cas systems present the potential to turn into the next-generation diagnostic tools, owing to its high sensitivity, and specificity since they can be multiplexed and reach SNPs (Single nucleotide polymorphisms) detection. B: Goals and Objectives The project aims to develop a high fidelity CRISPR kit for COVID-19 nucleic acid detection based on CRISPR-Cas12a and a probe-based lateral flow biosensor or handheld SERS system. The design uses: • use CRISPR Cas12a/b as the recognition system • Reverse transcriptase Loop-mediated isothermal amplification (RT-LAMP) as the signal amplification technique, and • Lateral flow strip and/or fluorescence reader or portable SurfaceEnhanced Raman Spectroscopy will be used for results readout. C: Methods The research project considers the following methodology approaches: i. Clinical evaluation of COVID-19 and impact assessment: Study the main content and key scientific and technical issues to be solved • Site selection and data collection: data available for lab analysis • Laboratory analysis: Identification of COVID19 • Data modeling and interpretation: Mapping of the disease status in the country • Manuscript writing and submission: Manuscript accepted for publication ii. Reverse transcription Loop-mediated isothermal amplification: Lab design, development and testing of the diagnostic test device kit • Primer design and synthesis: design of reporter molecule and capture probe (designed primers ordered using specific software) • Preliminary establishment of the RT-LAMP detection system: RT-LAMP system design and software modelling • Optimization of the RT-LAMP reaction system, Sensitivity test of the RT-LAMP detection method and Optimization of the RT-LAMP reaction system • CRISPR/Cas12 reaction design: Model designed and tested • Design of CIALFB onepot system: The device is operationally tested and protocol optimization (High sensitive and specific biosensor chip) iii. Test performance: Application of COVID-19 Rapid Diagnostic Test - On field testing of accuracy, sensitivity, specificity • Testing the kit on samples: COVID-19 detection in sub-clinical samples (with Wider pathogenic applicability) • Results comparison (with gold standard methods): Rapid vs. classic wet lab: Sensitivity, specificity and accuracy tested (with High sensitivity, specificity and accuracy) D: Expected outcomes Expected research results include: • Product of COVID-19 nucleic acid rapid test kit and a handheld SERS detector: developed CRISPR-based lateral flow biosensor for the detection of COVID-19 nucleic acid for on-site detection. This is a quick, easy and cheap Covid-19 detection kit with high sensitivity ( the detection limit can reach a level (10−18M), which is equal to a single microbial gene copy detection), high specificity (LAMP coupled with the specific recognition of gRNA ensures the ultra-high target detection), and Broad applicability: Freeze-dried products, easy to transport at room temperature • Application for one related invention patent • Publish one high-level scientific paper",2021,-99,University of Rwanda,60259.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Western Pacific,,,,Rwanda,Rwanda | China,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C19495,,Quantifying Productivity gains from using Artificial Intelligence (AI) in detecting COVID-19 patterns from Chest X-Rays,"A. Background Coronavirus disease (COVID-19) presents with non-specific respiratory symptoms that vary in severity and range from mild, severe to life threatening conditions requiring advanced mechanical respiratory support. Currently, identification of viral RNA in reverse transcriptase polymerase chain reaction (RTPCR) is regarded as the gold standard diagnostic test for COVID-19. However, RT-PCR has been shown to have limitations such as high number of false negatives and delayed results more especially in resource limited settings. Chest imaging has been used to complement clinical evaluation and laboratory workup in diagnosis and management of patients highly suspected or confirmed to have COVID-19 and most centers have reported literature on Chest CT manifestations in COVID-19 compared to other imaging modalities. In fact, there is developing literature identifying higher sensitivity of Chest CT for diagnosis of COVID-19 as compared with initial RT-PCR from swab samples. However, due to some limitations of CT in terms of infection control, availability in resource-limited areas, portability, some centers have used Chest radiography (CXR) and Lung ultrasound (LUS) to identify lung abnormalities pertinent to COVID-19. B. Goals and Objectives The overall objective of this study is to quantify potential productivity gains from use of Artificial Intelligence (AI) in detecting COVID-19 patterns from Chest X-Rays. Specific objectives are: i) to build highly accurate AI models capable of detecting COVID-19 patterns from Chest X-Ray, as well as ii) (ii) to create a setup that would allow us to measure improvements in speed of diagnosis and accuracy by radiologists assisted by AI in diagnosing COVID-19 from Chest X-Ray. C. Methods Researchers shall perform a retrospective and analytical study in which Chest X-Ray images of confirmed COVID-19 patients are studied by radiologists to detect the patterns in the image that are typical to COVID-19 infection. The first component of the study will comprise image annotation steps and will be done by expert radiologists based in Kigali, Rwanda using Insightiv's Teleradiology platform (i.e. online). They will use Chest-X-ray images collected by combining open-source and proprietary data from different partner institutions around the world. Phase 2 and 3 of the study will be done by expert software engineers and machine learning engineers based in Kigali, Rwanda, using cloud-based Graphical Processing Units (GPUs) to train different algorithms on detecting COVID-19 patterns from images annotated by radiologists, as well as on evaluating the algorithms. D. Expected outcomes By leveraging AI and Chest X-Ray imaging modality, the study will provide a cost-effective technology for risk assessment and early isolation of COVID-19 suspects, a win-win for suspected patients who are isolated and treated early without spreading the disease, and for the healthcare system which is overwhelmed with high cost and volume of patients",2021,-99,King Faisal Hospital,58252.17,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C19496,,Development of RT-Nucleic Acid Based Rapid Diagnostic Test for SARS-COV2,"LOD]). A multivariate regression model will be fit to explore the relationship between participant age and sex and testing RDT positive, after adjustment for COV RNA concentration vi) Packaging of NARDT: The NARDT will come as a kit containing the Twist DX Basic RT kit, separate Rnase inhibitor, probes and primers, and PCRD cassettes vii) Capacity building: Health professionals who are part of an ongoing COVID19 active case program across the country will be trained to use COVID 19 NARDT. A total of 20 health professionals will be demonstrating competence in completing the RDT procedure and interpretation of test results. D: Expected outcomes The project is expected to develop an accurate, highly sensitive and specific rapid test for SASCOV2. • Product: Validated new testing principle for real time detection of SARS-COV2 • Data: Produced the preliminary data on sensitivity and specificity of RT NA-RADT for SARSCOV2 The key outcomes of the projects are: • Improvement of sensitivity through temperature optimization and RT/MgOAC titration • New models for use of saliva samples in place of nasal/oropharyngeal swabs - nasal swabs considered as invasive and uncomfortable • Elimination of extraction step through use of optimized crude samples to make it a true POC/field test • Assessment of minimum template requirements - up to fg quantities of DNA • Multiplexing two primer-probe pairs e.g, Spike gp and RdRP and ORF3 or 8 all in one reaction for double detection of virus as the second step of validation",2021,-99,Rwanda Biomedical Center,60259.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda | Kenya,"Pathogen: natural history, transmission and diagnostics",Diagnostics, +C19497,,The impact of selenium supplementation in the treatment of COVID 19 positive patients in Rwanda,"A. Background Socio-economic pressure on health care systems and health care workers, fragile economies can suffer double given transmission mode and rate of COVID 19 if innovative strategies are not applied. Selenium supplementation has proven prevention evidence in cases of coxsackievirus and other viruses in many parts of the world. Little is known about the role of selenium in the treatment of COVID19 specifically. However, general knowledge of SARS viruses points to significant benefits of selenium in the management of enveloped viruses. Selenium deficiency in the body allows dormant enveloped viruses including SARS2-COVID19 through mutation synthesis to be more active and harmful strains. This enables these infections to progress into a disease that can range from mild to life-threatening diseases. Selenium is hypothesized to act as a transcriptase inhibitor hence leading to reduced viral replication. Selenium is known to boost the immune system and as a detoxifying mineral. B. Goals and Objectives The general objective of this project is to determine the impact of selenium supplement on COVID 19 treatment outcome. Specific objectives of this study are: • To determine the effect of selenium supplement on the immune response to COVID19. • To determine the effect of selenium supplement on reducing COVID 19 severity & length of hospital stay in positive patients • To determine the effect of selenium supplementation on COVID-19 on mortality rate. C. Methods All participants will receive the standard treatment of care irrespective of the experimental assignment. Unblinding will only be allowed in times of emergency related to side effects of the prescribed intervention. The trial intervention or placebo will be provided to the participant once daily or 12 hours, 8 hours, 6-hour schedules or even more to the discretion of the physician if the condition was critical. The intervention and placebo will be blinded to the investigator and patient. Coding will be used and will be disclosed to independent statistician during analysis time D. Expected outcomes The primary outcome measures for this study will be the changes in immune markers including CD4/CD8 T-cell counts, or change of cytokines (IL1, IL-6) and other inflammatory markers (CRP) that will allow us to determine the impact of selenium supplementation in the management of COVID19. For analyses of the CD4 T-cell count changes, patient samples will be taken at baseline (1st day of interaction), and at 7th day, 14th day, and every other 7th day until the participant exits from the treatment facility. Secondary outcomes will include viral suppression, mortality, and length of hospital stay, admission to HDU, Admission to ICU, mechanical ventilation and adverse events.",2021,-99,King Faisal Hospital,60234.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management", +C19498,,Genomic characterization and epidemiological Profile of COVID19 in Rwanda,"A: Background Evidence reveals that COVID-19 outbreak is of zoonotic origin, specifically bats seem to be the reservoir of COVID-19 virus, although the intermediate host(s) has not yet been identified. Corona Viruses (COVs) are enveloped positive-stranded RNA viruses with nucleocapsid. For addressing pathogenetic mechanisms of SARS-CoV-2, its viral structure, and genome must be of consideration. The transmission in Rwanda has been increasing overtime although COVID19 prevention measures and policies are being implemented. Although the WHO guided on diagnostic point of view and key biomarkers have been proposed, there remain gaps in understanding molecular patterns and genetic diversity in COVID 19 patients located in the African region. Besides, major gaps still exist in determining molecular factors influencing the susceptibility and vulnerability to severe coronavirus disease within a specific group of population. B: Goals and Objectives The project aims to determine the genetic pattern and diversity of severe coronavirus infection in infected patients and hence identify the outbreak transmission chain in Rwanda. More significantly, this study will provide understanding of the outbreak evolution in Rwanda and observing transmission dynamics through building phylogenetic trees. The project has the following specific objective: 1. To compare the diagnosis of Covid-19 from positive and control cases in Rwanda using both serological and molecular techniques and establish the relationship between the SARs-Cov-2 viral load and disease outcome 2. To determine the sequences of the Covid-19 positive cases reported in Rwanda and corelate with disease outcome 3. To determine the expression of the ACE-2 gene and protein receptor in the Covid-19 positive and control cases and corelate to clinical data 4. To perform protein-protein interaction analysis of the SARs-Cov-2 and ACE-2 receptor and truncated domains and establish its value for use as a diagnostic biomarker C: Methods Research methods: The study will employ a cross-sectional survey design that will target all Covid-19 confirmed or suspected cases treated in Rwanda at the sampling time. • Clinical Specimen and RNA extraction: Nasopharyngeal or oropharyngeal swab which were collected from symptomatic and symptomatic patients to detect SARS-CoV-2 by real-time reverse transcriptase (RT)-PCR will be used for RNA extraction with Biamp viral RNA mini kit (QIAGEN, Hilden, Germany) following the manufacturer's instructions. All specimens will be handled under a biosafety cabinet according to laboratory biosafety guidelines of Rwanda National Reference Lab. • Sequencing analysis: Using reverse transcriptase, cDNA will be synthesized from RNA extracted from the cultured cell medium in which the virus will be replicated. For this project the Whole Genome Sequencing will be performed using Illumina Mini-Seq machine 18 • Data Quality Assessment: Investigating quality control of sequence reads using FastQC. Fast QC is a Java-application that provides quality checks on raw sequence data coming from highthroughput sequencing pipelines. To improve the quality of data reads below an average score of 20 bp will be discarded for contamination. The reads will be trimmed using Trimmomatic. Trimmomatic is a flexible pipeline tool used for quality filtering. • Alignment and Assembling: Aligning the reads to a reference genome using a three-step process. Assembling and merging the read transcripts with an annotated file of the reference genome to produce a single annotation file using Cuffmerge. D: Expected outcomes The findings of the project will have the following clinical implications: • Screening the Covid-19 positive and suspected cases by both molecular and serological techniques would inform of the diagnostic ability of each of the tests and provide insight into the ability of each test to predict severe disease and guide into the triaging of patient • Determining the association between the viral load and disease severity would guide towards the evaluation of the management approaches and ensure that only very severe cases are managed by hospitalization while mild cases can be monitored at home or at outpatient facilities • Determining the SARs-Cov-2 recombination/mutation events by sequence analysis would inform of the disease transmission patterns and guide towards the adoption of management practices that are tailored as per the observed transmission patterns. • Assessing the ACE-2 levels in the Covid-19 samples in Kenya would inform of the role of this receptor in modulating viral infectivity and subsequently establish the susceptibility of the Kenyan population to Covid-19. Corelating the expression of this receptor with the patient clinical data would inform of the therapies to foster especially in patients with preexisting conditions. In addition, evaluating the role of this protein as a prognostic indicator would provide insight into the development of ideal point of care diagnostics to fast track disease detection. • Research outputs shall be communicated via scientific conferences and policy reports and subsequently published in open access peer reviewed international journals to inform a wider scientific community The key expected outcomes: • COVID19 transmission in Rwanda identified • New spots for vaccine and therapeutic development and hence contribute to the global efforts • Evidence on genetic diversity for COVID19 in African will be generated",2021,-99,Rwanda Biomedical Center,60259.47,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda | Kenya,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease pathogenesis | Supportive care, processes of care and management", +C19499,,A Technological Empowered Healthcare Delivery in the Era of COVID-19,"A. Background Having originated from Wuhan China, the Covid-19 virus is almost in all continents including Africa. Covid-19 has caused a collapse of social life due to the nature of how it is transmitted. However, some countries have begun to relax on strict lockdown measures, allowing social services including schools, markets and offices to reopen. The same is true of Rwanda, where social services such as markets, shops and supermarkets and restaurant have started to operate, which is a key step in reviving the economy. Although it will take time before life returns to normal, however, we highlight two aspects of social life where technology will prove vital in ensuring that business, schools, hospitals, office space and general day to day social life of people continues as smooth as possible. This can only be the case if measures are put in place that will boost public confidence in systems and places of work, shopping and mode of transportation. B. Goals and Objectives The main goal is to design, develop and deploy technology enabled preventive solutions to combat community spread of covid-19 through Mobile App integrated, effective health/mask screening kits and social distancing/Count alerts. Specific objectives are: 1. Design and develop a smart and portable vital sign Screener ""Health Neighbour Smart Kit (HeNSk)"" 2. Develop a low complexity facial recognition algorithm for mask checking and alert accordingly to allow or deny access/entry. 3. Develop a mobile app which interconnects public transport drivers, health personnel and ambulance drivers to allow them communicate and coordinate their efforts in taking necessary measures in handling potential Covid-19 cases. 4. Design and develop a smart distance checking camera system called ""Smart Distance Check Kit (SdChek) and alert accordingly. 5. Develop a low complexity distance checking algorithm that allows the camera to scan and check the distance between customers and also between customer and front desk employees. 6. Derive new insights through predictive analysis up on the collected data, query and visualize through dashboard plots. C. Methods The study seeks to provide legitimate IoT based solutions to aid the creation of an enabling environment leading to the improvement of the Rwandan society's resilience to mitigate the impact of Covid-19 pandemic. It is important that for any such solution(s), the beneficiaries of the solution should be involved during the development of the solution. This is because, although people may not know what the solution is, but they have first-hand experience with their problems. Hence, we leverage local knowledge by involving local IoT experts in the project team. Where a need for health expertise will be required, the relevant qualified health professionals will be consulted so as to ensure that we adapt our solution(s) to local context. It must be noted that to achieve the above highlighted objectives, existing off the shelf components will be used, making our solutions low cost and environment friendly. D. Expected outcomes The expected outcomes of this project include: 1. Screening Module: 20 • Health Neighbor Smart Kit (HeNSk) o Public is screened for health conditions and updated/alerted via App to concerned authorities automatically o Can be deployed in all public places which has more people gathering like public transports, Malls, Conference halls, Worship places, Marriage halls, market places etc. o Portable and deployable at any place of need • Face Mask Recognizer o Public is screened for masks, alerted and denied entry without mask. o Can be deployed in all public places which have more people gathering like public transports, Malls, Conference halls, Worship places, Marriage halls, market places etc. o Installable at any place of need 2. Smart Distance Module: • Smart Distance Check Kit (SdChek) o Automated queue management o Useful in any people crowded locations o Portable and deployable at any place of need • Distance alert o Alerts on distance reduction • Count alert o Prescribed count of people maintained based on meeting halls/marriage/worship places. o Count down displayed at the entrance, based on which doors can be opened or remains closed. o Smart App: o Mobile App has details synced with Health Neighbor Smart Kit (HeNSk) and communicates accordingly to health workers and ambulance drivers. o Data acquired can be analyzed further for meaningful insights and actionate accordingly. o Details and visualization charts area wise, gender wise (face recognition) etc., can be a possibility",2021,-99,University of Rwanda,60260.04,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,Digital Health,,,Rwanda,Rwanda,Infection prevention and control,"Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures", +C19500,,Analyzing the Resilience of Primary and Secondary Education Systems to Mitigate the Impact of COVID-19 Pandemic in Rwanda,"A. Background: Among the measures taken to limit the spread of COVID-19 is the closure of all public and private schools at all levels. This shift from physical student-teacher learning to online education impacted mostly the primary and secondary education systems. Short-term challenges are already manifesting including a new learning environment for primary and secondary school learners, the unplanned burden of expenses for poor families, job insecurity for private schools' teachers, maintenance of private schools' infrastructures, etc. With the current pace of this pandemic, more consequences are to be expected into the future. B: Objectives The general objective of the present study is to Analyze the Resilience of Primary and Secondary Education Systems to Mitigate the Impact of COVID-19 Pandemic in Rwanda. Specific Objectives are: i) Assessing the societal knowledge, perception, and attitude on the impacts of COVID 19 pandemic in Rwanda; ii) Understanding the role and interests of actors in improving the Resilience of Primary and Secondary Education Systems during and after COVID-19 pandemic in Rwanda; iii) Investigating the preparedness and effectiveness of ongoing e-learning platforms and tools in teaching and learning process at Primary and Secondary Education levels in Rwanda; iv) Considering and integrating stakeholders' suggestions to Mitigate the Impacts of COVID-19 pandemic on Primary and Secondary teaching and learning process and outcomes v) Establishing strategic approaches for accurate, timely, and consistent communication with the community (students, staff, parents, stakeholders) regarding COVID-19 preventive measures and the steps being taken to ensure smooth post-crisis continuity C: Methods This is a quantitative study to assess the knowledge and attitudes regarding Covid-19 among children, adults, and disadvantaged groups in sequential steps: Step 1: We developed a set of categories of needs relating to social exclusion and identity formation based on existing knowledge in literature; Step 2: We discussed the established categories in round-table consortium meetings Step 3: We established appropriate sites for interview rounds as well as an initial list of potential respondents to include a cross-section of the Vulnerable population, based upon location, gender, age, education and current means of livelihood; Step 4: We established categories form the base for the first round of semi-structured interviews with 20 members of the vulnerable Households Step 5: In the second round, 80 interviewees will be shown a card with a list of categories 22 Step 6: In the third round of interviews a second group comprised of the strategic actors that influence how Vulnerable are perceived (community leaders; government officials; international actors; members of the popular media; development, human rights, and indigenous peoples NGO workers) and a cross-section of 25 ordinary members of neighboring communities, will be asked to comment on the list of categories of identity-formation and exclusion. Step 7: A picture of Every student needs of personal contact and exclusion will be drawn based upon existing knowledge, paying particular attention to the links that are made between how their adequate hardware/software/internet access and social exclusion. D: Expected outcome are i) The research findings will lead to an overview of the existing COVID-19 situation (nationwide) to establish a better and more systematic understanding of COVID 19 in regards to primary and secondary education systems ii) The study will uncover study guided strategies to mitigate negative impacts on teaching and learning to support and build resilient, sustainable and inclusive primary and secondary educational systems to foster socio economic development and well-being. iii) Researchers and Academic staff from University of Rwanda collaborate with Civil society NGO in this research to come up with research findings and recommendations to guide policy makers in the setting and implementation of recovery policies iv) A citizen surveillance system is established (oversight of access to and quality of preventive measures)",2021,-99,University of Rwanda,60220,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Vulnerable populations unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda | Zimbabwe,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Communication | Social impacts, +C19501,,Mitigating the social and economic impact of COVID-19 pandemic in private higher education of Rwanda.,"A: Background: COVID-19 is a humanitarian and societal crisis of unprecedented speed and scale. It has both immediate and long-lasting implications for how people work and participate in society. Private universities, which enroll over half of Rwandan higher education students, are concerned by COVID19 pandemic not only result in a loss of students, but academic staff as well. The private universities predict high numbers of dropout cases due to COVID-19. The students who usually pay for themselves are employees in private companies which are either suspended or unable to pay them. For the others source their school fees either from parents or other sponsors, all of whom are socially and economically hit by the pandemic. B. Goal and Objectives The goal of this project is to provide to direct beneficiaries such as the students, lecturers, parents, universities the social and economic situation analysis as a way to create resilience for curbing the effects of COVID-19 Objectives: 1. To analyze the social and economic situation of private higher learning institutions pre and during COVID-19 Pandemic in Rwanda. 2. To identify the social and economic effects faced by private higher learning institutions during COVID-19 Pandemic in Rwanda. 3. To suggest the strategies as solution to COVID-19 Pandemic educational disruptions in private higher learning institutions in Rwanda. 4. To assess the contribution of private HLIs resilience to mitigate the Impact of COVID-19 Pandemic in Rwanda. C. Methods  The research project will sample purposively the private higher learning institutions in Rwanda.  The information for this study will be gathered through questionnaires and interviews  The research project will work on large amounts of textual information and systematically identify, categorize and excerpt information desired to answer research questions of this research project.  The findings will be disseminated through different ways like academic conferences, publication, door to door messages, public service announcements, news releases and government or community websites D: Expected Outcomes are:  Inform on the strategies as solutions to COVID-19 Pandemic educational disruptions in private higher learning institutions.  Document on contributions of private HLIs resilience to mitigate the Impact of COVID-19 Pandemic.",2021,-99,"University of Tourism, Technology and Business Studies",43425.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts, +C19502,,Bioethanol and hand sanitizer production from sugar cane molasses to quickly respond to their local increasing demand towards COVID-19 pandemic.,"A: Background This project intends to assess feasibility of producing Aloe vera-based hand sanitizers using bioethanol from sugar cane molasses and other vegetable by-products to mitigate Covid- 19 pandemic. By using hand sanitizer, it is a convenient way and less time consuming to ensuring hand hygiene which will lessen the spread of Covid-19 pandemic. The requirement of hand sanitizers is expected to continue for an extended time. Thus, the ethanol availability has to be ensured in order to help people meet the demand for adequate hand hygiene. Because of Covid-19 pandemic the need for sanitizers is higher, yet availability is low or high cost. Yet the production of bioethanol from edible agricultural products may cause rise of cost of these crops leading to food insecurity. Bioethanol derived from agriculture waste, which is most abundant at global level, is the best option. B: Goals and Objectives The overarching goal of this research project is to assess feasibility of production, and operationalize a bioethanol plant and to develop Aloe vera-based hand sanitizers. Specific objectives: i To install and operationalize a bioethanol processing plant at NIRDA Research Center in Huye District; ii To initiate the bio-ethanol production from sugar cane molasses and other vegetable by-products for a standardized hand sanitizers production; iii To formulate Aloe vera-based hand sanitizers and conduct its efficacy and safety evaluation C: Methods and Materials We will initiate a bioethanol processing unit. The NIRDA ethanol pilot plant stopped after 1994 Genocide against the Tutsi. A pilot plant was re-operated up to 2007. However, because of some important parts were completely damaged, NIRDA bioethanol production plant ceased its activities. We will use sugar cane molasses from Kabuye Sugar works, which are not valued and are regarded as by-products and considered as waste or simply used as source of energy. This molasses are important key materials for bioethanol production. The combination of Aloe vera gel with glycerol and propylene glycol at appropriate proportion will be used as humectant. The Aloe vera will be supplied by local cultivation companies and processed in NIRDA. Other excipients including: • The fermentative yeast Saccharomyces cerevisiae, nutrients and citric acid for ethanol production • Carbomer powder which is used as clear gel thickner, emulsion stabilizer and suspending agent • Glycerol which is used as humectant, moisturizing, emollient, skin softening. Skin repairing, prevent skin barrier from drying • Methyl paraben, methyl/Propyl parahydroxybenzoate which is used as antimicrobial agent designed for preservation of a wide range of cosmetics, toiletriess and topical pharmaceuticals. • Triethanolamine which is used as pH adjuster The Procedure will be as follows: • We will use molasses from the tanks diluted with water to obtain the sugar concentration around 10-15%, • We will use a yeast culture tank, with nutrition supply of ammonium and magnesium phosphate or sulfate, • We will use diluted and treated molasses and the yeast from storage fed to the fermentation chamber, • Fermentation takes around 30-70 hours based on the pH, temperature and sugar concentration • The rectification process will be used to produce 95% ethanol Activities and Milestones Some of planned activities in the project are following as shown at Fig 1 below: • Organization of first research meeting • Conducting the technical Audit by planning & monitoring team • Preparation of MoU and contracts for equipment, excipients and raw material acquisition • Aloe vera planting materials acquisition • Bioethanol formulation from sugar cane molasses • Aloe vera gel-based hand sanitizer formulation D: Expected outcomes The expected outcomes are the following: • Bioethanol processing plant installed and operationalized; • Bioethanol with pharmaceutical grade produced; • Aloe vera-based hand sanitizers formulated and produced",2021,-99,National Industrial Research and Development Agency (NIRDA),60035.18,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | South-East Asia,,,,Rwanda,Rwanda | India,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures", +C19503,,Design and development of emergency ventilator,"A. Background The novel COVID-19 is in the family of SARS and MERS coronaviruses and its implications include high fever, severe cough, difficulty breathing pneumonia, organ failure and death. This means that if the respiratory system fails, a patient will need an artificially breathing system and we can daily see, then number of victims is exponentially growing this will surely make some shortage in ventilators and manufacturers ( from rich countries) will be concentrated with saving first their countries this make African countries to not have access to ventilators. B. Goals and Objectives The main objective of this project is to design and develop an emergency ventilator which will support COVID-19 Patients in this pandemic period. However, this emergency ventilator can also be used in private or public hospitals and ambulances to save multitude of lives with breathing difficulties. Specific objectives are: • Design and develop the mechanic part. • Design and develop the control part. • Perform clinical testing parameters • Enhance technology integration in the health sector for rapid development of a more efficient and cost-effective healthcare service delivery system in Rwanda. • Train more biomedical engineers, enabling an environment for hands-on skills development and R&D capability in biomedical engineering and e-health. C. Methods For developing a ventilator, expertise from different field is required. For the first prototype the project gathers together electrical, mechanical and biomedical engineers the team also included some medical doctors to help for clinical concepts. Basically, the development of a ventilator follows 3 different concepts: • Clinical concept for the ventilator • Mechanical design for the ventilator • Control and electrical concept for a ventilator D. Expected outcomes At completion to the project, following are expected outcomes: • A certified emergency ventilator • More jobs which will be created, when it comes to mass production • Internship and training for students",2021,-99,Rwanda Polytechnic IPRC Kigali,60260.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Europe,,,,Rwanda,Rwanda | United Kingdom,Clinical characterisation and management,"Supportive care, processes of care and management", +C19504,,Design and Manufacturing of a Smart COVID19 Tracing System,"A: Background The premise of this research is based on some challenges for contact tracing including incomplete identification of contacts, inefficiencies in paper-based reporting systems, and delays in steps of identification of contacts to isolation of suspected cases of COVID-19 among contacts. This research project will assess feasibility of using a digital solution that consists of hardware and software using RFID (Radio-Frequency Identification) technology with a non-contact temperature measurement to manage dynamic relationships between cases and contacts. This is because contacts may have links to multiple cases, and may become cases that generate further contacts. At software level, the contact history data can be processed centrally, typically either by a health authority like Rwandan Ministry of Health MINISANTE, the Rwanda Biomedical Center (RBC) or by individual devices. B: Goal and objectives The overall goal of this research is to develop and demonstrate 'made in Rwanda' innovative products, which are effective non-contact temperature measuring machines for prevention and management of COVID-19 infection and other infectious diseases alike. Specific Objectives: i) To develop Digital tool for monitoring health conditions and storage of personal information to easy tracing when a person is found with COVID-19 ii) To measure the effectiveness of proposed innovative machine against the spread of COVID-19 infection C: Methods The process of contact tracing in Rwanda currently follows the following steps • COVID-19 case investigators identify all clinical data. • Use of human memory history to recall all contacts during the 2 days to 14 days window • Development of a roster of close contact and anyone who was in touch with the index case within the window period in time and space (within 1 m), • An active contact follow-up is therefore initiated by the command post to monitor, on a daily basis, any sign leading to possible cases. D: Expected results, outputs and Outcomes are The project will result in the following: • Potential reduction of spread of COVID-19 as a result of identifying infected people before infecting others • Reduced loss of time and money or resources to conduct COVID-19 test for people with no basic symptoms Expected Outputs include: • The project intends to make devices to test with people on eight (8) different institutions before they are distributed around the country. To implement this project, investigators shall host the software for data storage and monitoring on servers and register at least 500,000 users • The project shall implement nine (9) functional non-contact temperature measuring devices • The project study involves five (5) UR-CST students with different skills • Hosted software to track measurements from the devices in the real-time • Training of six (6) personnel from UR-CST to support the implementation and scale up the project The Expected outcomes are • Reduction in spreading COVID-19 as a result of people's awareness of their health conditions • An increment in people's awareness about COVID-19 as a result of regular temperature measurement on different sites. Only further evaluation and diagnostic testing may be required for people with high temperature to determine if someone has a COVID-19 infection. • Reduction in time and money spent on tracing contacts and unnecessary tests",2021,-99,University of Rwanda,51218.32,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,Digital Health,,,Rwanda,Rwanda,Infection prevention and control,Restriction measures to prevent secondary transmission in communities, +C19505,,Mathematical Models for Predicting and Monitoring the Impact of COVID-19 in Rwanda,"A: Background: To control human and animal diseases, the mathematical modeling and simulation are very important tools since that they can provide projections of the likely future, provide descriptions of the natural history of infections at a population and individual level, and provide insights into the impact of possible interventions. The dynamical biological processes are better modeled by means of systems of deterministic differential equations (ordinary (ODE), partial (PDE), or delay (DDE). Scientists have contributed a lot in modelling the spread of epidemics and the plans for controlling the spread. The development of the mathematical model of COVID-19 should take into account the known specific characteristics of this new disease. In Rwanda, the flow of COVID-19 can be modeled using deterministic mathematical compartmental epidemic models, stochastic differential equations (SDEs) and network models B. Goal and Objectives The goal of this project is to develop a mathematical modeling framework for predicting and monitoring the COVID-19 pandemic in Rwanda. Developed models will help in understanding the disease transmission dynamics, as well as give insights into the effectiveness of control strategies by providing forecasts of the disease burden on the country and hence of eventual health care saturation, infrastructure and facilities needs hospitals, in quarantine centers. Objectives: 1. Build a deterministic mathematical model able to capture the dynamic transmissions of COVID-19 in Rwanda; 2. Build a stochastic model able to capture the inherent random, and uncertain factors influencing the spread and control of COVID-19 in Rwanda; 3. Develop a graph-based network model for COVID-19 propagation in Rwanda based on a random network of contacts between individuals; 4. Develop a statistical framework to analyse the response and impact of COVID-19 pandemic in Rwanda from a multi-discipline perspective and investigate the eventual situation of endemicity of COVID-19; 5. Connect the developed models to existing database through a well-designed App to automate data processing and produce a dashboard to allow quick actions from health care authorities. C. Methods The model will be constructed by using deterministic, stochastic and networking approaches.  Study design: The total effective Rwandan population size will be divided into eight compartments: Susceptible (S), Exposed (E), Quarantine (Q), Infectious (I), Undocumented infected (Iu), Hospitalized (H), Recovered (R) and Dead (D); that is the mathematical model SEQIHRD. All the compartments will be linked by parameters to be estimated using data. Two 30 cases will be studied (1) the population is assumed to be closed (there is a pure confinement or lockdown) and (2) the post lockdown where the population is free to move even borders are open, i.e. the population is living with COVID-19.  Data collection: secondary data will be used. They will be collected from clinical records of RBC (Rwanda Biomedical Centre) and other well established data bases. During the analysis of post lockdown, researchers will be interested in effective measures used to contain the outbreak. Therefore, primary data will be collected using questionnaire that will be designed according to the needed variables.  Epidemiological models: Through the transfer diagram, the compartmental mathematical model SQEIHRD will be developed in form of Ordinary differential equations by considering the special characteristics of the pandemic in Rwanda. The deterministic model may then be extended into a stochastic model and network model by taking into account the random fluctuations observed along the time of the outbreak.  Model parameters estimation and validation: The estimation of parameters will be done using Least Square Method and others may be found from literatures or medical experiments. Once the model is validated as accurate it will be used to study different scenario specified in the call. It will be used for monitoring and prediction using the dashboard to allow quick actions from authorities in charge of COVID-19. Furthermore, a statistical model capturing all the collected data can be identified and used for prediction. D: Expected Outcomes are:  Improved scientific understanding of the disease  Inform decision making on easing lockdown measures  Inform policy makers and health care professionals for post-corona strategies  Preparedness for eventual future infectious diseases",2021,-99,University of Rwanda,60139.33,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Europe,,,,Rwanda,Rwanda | Finland | Uganda | Tanzania,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C19506,,Longitudinal datasets hub for predicting and monitoring COVID-19 evolution in the community and mitigation measures outcomes in Rwanda (Predict Project),"A: Background: The coronavirus disease 2019 (COVID19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread to the whole world in a very fast manner. All countries worldwide elaborated strategies to prevent and manage COVID-19 and mitigate its effects. Diagnostic tests have been designed to detect COVID-19 ARN or antibodies against the virus. Strategies to prevent and control COVID-19 and mitigate its effects have been initiated in all countries at different levels. However, these strategies need continuous adjustment as the characteristics and the dynamics of the virus are progressively discovered. There is need for accurate data on the prevalence, incidence and evolution of the disease. This project comes to add new knowledge on the dynamics of COVID-19 in Rwanda by highlighting the trends in its characteristics. B. Goal and Objectives The goal of this project is to provide data and predictions models for the control and management of COVID-19. Objectives: 1. To gather all existing collected data on COVID-19 in Rwanda in a single data hub server. 2. To collect prospective data on COVID-19 in the community through mobile surveys applications 3. To leverage both traditional mathematical modelling techniques, statistical methods and machine learning methods for prediction models. 4. To provide a live monitoring dashboard for the burden of COVID-19 in the community but also the potential impact on hospital/treatment centre admissions and overall infection rates 5. To predict the impact of various public health measures on the pandemic evolution in the country C. Methods The set objectives will be achieved through 2 approaches: Building a longitudinal datasets hub for predicting and monitoring COVID-19 evolution in the community and in health facilities:  Gathering all existing datasets on Covid-19 in Rwanda (National Joint Taskforce for COVID-19, RBC, MOH)  Integrating other data collected from ongoing cohorts or similar covid-19 projects, including a) the International citizen project to assess adherence to public health measures and their impact on the COVID-19 outbreak (20-country research consortium led by Antwerp University); and b) the National Institute of Statistics of Rwanda (NISR) data.  The survey that will leverage mobile App questionnaires: A minimum of 1200 people per district (36.000 person throughout Rwanda) will be required for mobile App responses weekly (minimum frequency being 2 times per week). A minimum sample of 200 persons per district will be reached out by the data collector with validation call or face-to-face questionnaire. The 32 questionnaires will be translated in 3 languages, Kinyarwanda, English and French in Mobile applications Building an analytical layer on top of the Data Hub, which will leverage both traditional mathematical modelling techniques, statistical methods and machine learning methods for predicting and monitoring the burden of COVID-19 in the community, on hospital/treatment centre admissions and overall infection rates and monitor the impact of various public health measures on the pandemic evolution in the country D: Expected Outcomes are:  Establishment of a robust database gathering various source of data useful for basic epidemiological studies and daily policy-driven decisions but ultimately to be used for the predicting model.  Improved understanding of national, regional and international dynamics of COVID-19 as a result of this study findings aggregated with other research findings.  COVID-19 prevention methods and strategies will be developed based on study findings  COVID-19 pandemic controlled through application of the findings from this study",2021,-99,University of Rwanda,60260.45,Human Populations | Other,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Europe,,,,Rwanda,Rwanda | Belgium,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures, +C19507,,Predicting the risk of SARS-Cov2 infection and co-morbidity and Reducing Socioeconomic Impacts: Identification of high-risk population,"A: Background: Sub-Saharan Africa is sadly familiar with epidemies, but SARS-Cov2 is posing unprecedented threats. Paradoxically, its low-to-medium clinical severity slows and hampers the early recognition of cases, and the supposedly high number of asymptomatic or pauci-symptomatic individuals is seen as a major engine for contagion. From a clinical point of view, the information on why some people remain asymptomatic, other develop mild conditions, some other, instead, develop serious pneumonia, microtrombosis, vasculopathy and eventually die is still scanty. What is known, is that SARS-Cov2 infection can induce a hyper immune response and a systemic inflammatory state. Understanding why this happens to some but not to the others, is crucial for stratification of patients and efficient use of medicines and medical resources. B. Goal and Objectives The goal of this project is to evaluate the oxidative status of a population of individuals (for example, a community center, a University) that can allow the adoption of personalized measures to reduce both the clinical and the socioeconomic impacts of possible outbreaks Objectives: 1. To identify the communities, with risk of becoming hotspots of future outbreak or regions with identified cases of infection. 2. To measure the plasma redox state within the identified communities. 3. To map the chosen communities according to the redox state of their components, and this will become the background signal for that community 4. To set guidelines to the Community Health facilities to implement a system of control of the redox markers among the population C. Methods Most of the work will include analytical laboratory analyses using mainly the following techniques:  Engagement of Community Health facilities, hospital and universities to develop and establish 'electronic medical files' for the population to delineate a predictive statistical model which can be used to early detection of outbreaks and/or hot spot  Quantification of the oxidative status using FRAS Technologies. Two tests will be performed: dROM (Reactive Oxygen Metabolite) and PAT (Plasma Antioxidant Test) tests D: Expected Outcomes are:  Establishment of systematic evaluation of the plasma redox state of a community which goes beyond the contingent case of the SARS-Cov2 pandemic  Inform on strategic plan for health sector in Rwanda  Implementation of the district-wide (with potential for nation-wide) approach where cuttingedge of scientific concepts are immediately translated into technological applications, with the ambition to significantly improve the reactivity of the communities and to reduce the social and economic burdens linked to COVID-19 outbreak.",2021,-99,Institut d'Enseignement Supérieur de Ruhengeri,60259.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Europe,,,,Rwanda,Rwanda | Italy,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease susceptibility | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions, +C19508,,"Predicting the infections, evolution and outcome of COVID-19 pandemic in Rwanda using SIR model","A: Background: Since the first case was reported in Rwanda on March 14, 2020, various measures have been taken to slowdown the spread of the virus. However, due to its high infection rate and lack of virus immunity to everyone, the number of infected persons have continued to increase. The rising numbers of COVID19 infections have the potential to devastate the health care system in Rwanda if the spread is not controlled. There is a need of a reliable, country-specific forecast model to help in the prediction of infections and evolution of the virus. Such a model is necessary to monitor and assess the impact of the policies taken to slowdown the spread and consequences of the COVID-19 virus B. Goal and Objectives The goal of this project is to build a prediction model which provide a picture of the predicted progress of COVID-19 in Rwanda and test the impact of limiting the contact risks under the precaution measures taken to slowdown the spread of the virus Objectives: 1. To measure the transmission rate of the virus in Rwanda and determine the basic reproduction number (R0) of COVID-19 in Rwanda; 2. To assess the recovery rate of COVID-19, estimate the number of infectives, and the cumulative morbidity of COVID-19 in subsequent periods; 3. To estimate the risk of healthcare capacity in terms of access consideration, functional requirements, location, and uncertainties associated with the spread of the virus. C. Methods · The data will be collected from two sampling sources: Sampling Source 1: The first sample will utilize the list of all COVID-19 patients and recoveries as the sampling frame. From the selected sample, the primary data will be collected and used to assess the infectivity, incubation, and recovery among different population categories. Sampling Source 2: The second sample will be selected from the list of all health facilities in Rwanda. The primary data will be collected from the selected sample and analyzed to assess the healthcare capacity and determining which health facilities are capable of receiving COVID-19 patients in case the virus continues to spread in Rwanda · Prediction model To build a mathematical prediction model of COVID-19 pandemic in Rwanda, an extended Susceptible - Infected - Removed (eSIR) model was used. While the standard SIR model assumes constant transmission rate, the extended SIR model assumes a varying rate of virus transmission from infected person to a normal person, which is due to different measures taken to slow the spread of the virus like lockdown of cities, social distancing, and others. 35 D: Expected Outcomes are: · Availing a mathematical prediction model that will be used to control the spread and the outcome of the pandemic in Rwanda specifically, · Inform on the impact assessment of preventive measures taken by the government of Rwanda in response of flattening the curve of infection, · Inform on the healthcare capacity in terms of availability of functional requirements in case the virus continues to increase in Rwanda.",2021,-99,University of Rwanda,60259.47,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa | Americas,,,,Rwanda,Rwanda | United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility, +C19509,,Impact of COVID-19 on surgical care in Rwanda,"A: Background The COVID-19 pandemic has profoundly affected health care delivery. With the increasing number of cases, health care systems around the world have faced strains, with shortages of health care workers, personal protective equipment (PPE), ventilators and other resources. Surgical practice has faced dramatic changes in this pandemic. In certain parts, elective surgery and clinics have been cancelled to prioritize resources for the increasing COVID-19 patients and decrease risk to patients and health care worker. In Rwanda, access to surgical care is limited with insufficient surgical capacity and high unmet surgical needs, with most of the care provided in urban areas. In various surgical specialties, patient waiting lists are long with insufficient operating room space and hospital beds. Patients must wait for long periods to get the care they need. With the surge of COVID19, there is a need to study to what extent COVID19 pandemic has affected surgical care delivery in Rwanda. The impact will be assessed in terms of surgical volume, elective versus emergency cases by specialty, transfer patterns to referral hospitals and outcomes (mortality, morbidity and length of hospital stay). Knowing the impact of the pandemic on surgical care will enable developing measures to address the surgical burden and provide appropriate care to patients in need, as well eventually putting in place strong measures for possible future public health crises. B: Goals and Objectives: The project aims to assess the impact of COVID-19 on accessibility to surgical care in Rwanda. The project has the following specific objective: i) To determine the number of surgeries performed (Emergencies vs electives by specialty) over a 15 weeks period from March 22nd to June 30th, 2020 (During COVID-19 outbreak) ii) To determine the number of surgical outpatients by different surgical specialties received over a 15 weeks period from March 22nd to June 30th, 2019 (Before COVID-19 outbreak) iii) To determine type of surgical cases managed during Covid-19 pandemic lockdown across different surgical specialties iv) To compare both periods (before and during COVID-19 outbreak) as far as number of cases, inhospital mortality, morbidity, and length of hospital stay are concerned with respect to different surgical specialties v) To identify challenges encountered by surgical care providers to provision of surgical care over the 15 weeks period during COVID-19 pandemic lockdown vi) To develop a tool kit to be used by Rwandan Surgical community during next pandemic outbreaks C: Methods The project will be a mixed method study with concurrent explanatory design: • Study site: Multi-centric, nation-wide, including private and public hospitals that provide surgical care. Private hospitals will be stratified into hospitals and polyclinics whereas public institutions will be stratified into two categories: referral hospitals (university teaching hospitals, provincial and other referral hospitals) and district hospitals (DHs) • Sampling technique:  Stratified multi-stage cluster sampling will be used  Qualitative data will be collected through focus group discussions (FGDs) using a semi structured interview guide: A focus group discussion engaging 6 to 12 people made of 37 surgeons, anesthesiologists, gynecologists, and theatre nurses will be constituted to foster active participation and in-depth discussion  Quantitative data will be collected through cross-sectional survey using a preestablished questionnaire • Data collection, processing and analysis: Data on surgical cases will be summarized and cleaned in MS Excel spreadsheet. The questionnaire will be completed online using survey monkey, data will be extracted in excel format cleaned and coded, then analyzed using STATA. D: Expected outcomes The findings of the project will have the following clinical implications: • Screening the Covid-19 positive and suspected cases by both molecular and serological techniques would inform of the diagnostic ability of each of the tests and provide insight into the ability of each test to predict severe disease and guide into the triaging of patient • Determining the association between the viral load and disease severity would guide towards the evaluation of the management approaches and ensure that only very severe cases are managed by hospitalization while mild cases can be monitored at home or at outpatient facilities • Determining the SARs-Cov-2 recombination/mutation events by sequence analysis would inform of the disease transmission patterns and guide towards the adoption of management practices that are tailored as per the observed transmission patterns. • Assessing the ACE-2 levels in the Covid-19 samples in Kenya would inform of the role of this receptor in modulating viral infectivity and subsequently establish the susceptibility of the Kenyan population to Covid-19. Corelating the expression of this receptor with the patient clinical data would inform of the therapies to foster especially in patients with preexisting conditions. In addition, evaluating the role of this protein as a prognostic indicator would provide insight into the development of ideal point of care diagnostics to fast track disease detection. • Research outputs shall be communicated via scientific conferences and policy reports and subsequently published in open access peer reviewed international journals to inform a wider scientific community The key expected outcomes: • COVID19 transmission in Rwanda identified • New spots for vaccine and therapeutic development and hence contribute to the global efforts • Evidence on genetic diversity for COVID19 in African will be generated",2021,-99,King Faisal Hospital,60260.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Council for Science and Technology (NCST) Rwanda,Rwanda,Africa,Africa,Africa,,,,Rwanda,Rwanda | Tanzania,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery, +C19543,202102VS1,"COVID-19 Variant Supplement - A low-cost, portable, and decentralized microfluidic device for detecting SARS-CoV-2 neutralizing antibodies","Serological surveillance provides population-wide immunity status in a timely manner, which is important evidence in directing public health policy during the COVID-19 pandemic. Immunoassays are serological tests that can measure antibody levels to an infectious disease, and are being rapidly employed to identify individuals with potential immunity to SARS-CoV-2. Although immunoassays can quantify antibodies in a sample, they do not directly measure neutralizing antibodies (nAbs). Tests currently available for nAbs are expensive, labour intensive, require high biosafety containment, and are can only be preformed in centralized national laboratories. Low-cost, rapid, decentralized testing for SARS-CoV-2 nAbs will expedite serological surveys and help evaluate herd immunity and vaccine effectiveness. The goal of this project is to develop a fast and cost-effective assay to detect nAbs for SARS-CoV-2 and with reduced biosafety requirements for immediate distribution. This assay will then be integrated into a paper-based microfluidic device for portable testing that uses a one-step assay capable of separating out antibodies from whole blood. The development of new diagnostic tools will be critical for serological surveillance during and after the current COVID-19 pandemic and can help direct Canada's response to prevent further outbreaks. Low-cost and portable serological testing will also enable low- and middle-income countries to perform high-quality serological surveys and these tools will be of immense value to displaced populations (i.e. refugees). Furthermore, rapid and reliable screening of plasma samples for neutralizing antibodies will provide a valuable resource for the evaluation of current vaccination and antibody-based therapeutic approaches towards SARS-CoV-2.",2021,2022,Ryerson University (Toronto),39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2021 +C19544,202102VS1,COVID-19 Variant Supplement - Analysis of Antibody Neutralization Efficiency and Cellular Immunity in SARS-CoV-2-Positive Individuals Identified in At-Risk Individuals,"As the COVID-19 pandemic continues its deadly course around the globe, research efforts are closely focused on viral immunity, antibody responses, and vaccine development. Increasing data from multiple reputable international medical sources now indicate that exposure to the COVID-19 virus induces an antibody response in nearly all exposed individuals. However, questions remain about the protective value of these antibodies against repeat exposure to the virus and how long this protection will last. Furthermore, it is unclear whether there are differences in the virus-neutralizing ability of antibodies produced by asymptomatic carriers of the virus and individuals that develop severe COVID-19 infection. Answers to these important questions will enable us to predict the likelihood of additional waves of COVID-19 as well as inform public health efforts and vaccine development. For our study we will recruit a total of 1,000 healthy primary school teachers, daycare personnel, frontline medical workers in hospitals, and elderly people living in retirement homes. We will monitor them every two weeks for the virus and monthly for antibodies. We will regularly report back the data to the participants. The information learned from our laboratory will have five major outcomes: 1) It will enable early detection of infection and thereby greatly reduced the spread of the virus; 2) We will acquire a better sense of the numbers of asymptomatic and symptomatic individuals exposed to COVID-19; 3) Antibodies in the blood of those infected will be tested to see how well it can neutralize the virus; 4) Critical information about immunity to COVID-19 and how long the immunity will last will be shared with the scientific community and local/regional/national health authorities; and 5) This new knowledge will help vaccine developers make the right decisions about how to create their vaccines and how to give them to all of us.",2021,2022,University of Ottawa,39500,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics",2021 +C19545,202102VS1,COVID-19 Variant Supplement - Assessing the impact of the COVID-19 pandemic on social and health outcomes among young people: A mixed-method comparative analysis in Canada and France,"Youth (<30 years) are among the most at risk for longer-term social and health consequences due to COVID-19-related public health measures (e.g., physical distancing) and the associated social and economic impacts, including unemployment, as well as isolation from their social networks and disruption to their education during key periods of the early life course. To advance evidence and to inform adaptive social, economic and public health responses among youth, we are prepared to rapidly launch a one-year multi-site mixed-methods study. Our aim is to generate new context-sensitive and population-specific data to document how policy and program responses can be optimized to improve the lives of youth in two key international settings: Canada and France. While both Canada and France share some commonalities (e.g., high-income countries, publicly funded health care systems), there are many important contextual differences (e.g., severity and evolution of national and regional COVID‑19 curves, economic support/employment insurance programs, community-based responses) that will benefit from empirical investigation as they relate to youth population health. We will conduct a multi-site concurrent mixed-methods study that includes: (i) a series of longitudinal qualitative research activities including semi-structured interviews with youth from across different jurisdictions in Canada (n=30) and France (n=30); (ii) interviews with key stakeholders (n=10 in each setting); and (iii) two national online cross-sectional surveys in both Canada and France with youth (at 6-month intervals). Throughout the duration of the proposed study we will engage in integrated knowledge translation and exchange (KTE) activities to systematically engage in rapid-cycle evaluation and advance actionable findings, including findings that are of relevance to national, federal and local policies and programs that can have an impact on youth social and health outcomes.",2021,2022,University of British Columbia,39500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Europe,,,,Canada,Canada | France,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19546,202102VS1,COVID-19 Variant Supplement - Bespoke transition state analog inhibitors of SARS-CoV-2 3CL and PL proteases,"SARS-CoV-2 is devastating global health and economies. Rapid development of antiviral drugs is critical to treat disease in the short term and beyond. Logical antiviral targets are the proteases 3CLpro and PLpro, responsible for processing of long chains of linked viral proteins produced during viral reproduction. 3CLpro and PLpro are enzymes that harness pac-man like activity to clip the chains into individual proteins. This cleavage process is essential for formation of new disease causing virus. If you block the pac-man activity, you stop the virus in its tracks. Similar types of viruses have been targeted very successfully by drug development in other important global viruses such as HIV. Understanding inhibitor binding to 3CLpro and PLpro at the atomic level is central to antiviral drug development. We are harnessing our significant expertise in xray crystallography and single particle cryoEM, biophsyical techniques that allow us to determine atomic pictures of these proteases in the presence of bound drug. Leveraging our prior work on similar enzymes with international leading antimicrobial pharmaceutical teams we have identified tight binding drug leads that take advantage of the unique features of these enzymes. We aim to optimize these compounds through structure-guided techniques (using our atomic blueprints so to speak) and the antiviral drug discovery pipeline of our industry partner.",2021,2022,University of British Columbia,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19547,202102VS1,COVID-19 Variant Supplement - BLT-Lung mice for the rapid evaluation of COVID-19 therapeutics,Controlled animal studies of candidate anti-COVID-19 therapies are required to rapidly identify the most promising drugs and safely advance them to trials in human subjects. The animal models that best predict what therapies will perform similarly in humans are those that closely replicate the human condition. Primates closely resemble humans but rapid high-throughput evaluation of drugs in this animal model is not feasible for economic and ethical reasons. We are producing a unique mouse model that contains human lung implants that support SARS-CoV-2 infection and a human immune system capable of responding to the infection. This animal model thus closely replicates COVID-19 disease seen in humans. These mice are in high demand to evaluate drugs that have already proven safe for the treatment of other diseases and drugs showing strong anti-SARS-CoV-2 effects in the laboratory. We will produce these mice and rapidly assess some of the most promising therapeutic candidates that have been identified as potential treatments of COVID-19. These studies will allow us to rapidly determine the impact of numerous promising compounds in a sophisticated animal model that closely resembles human COVID-19 disease in order to better predict their success in humans and speed their course towards clinical use.,2021,2022,University of Saskatchewan,39500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2021 +C19548,202102VS1,COVID-19 Variant Supplement - Canadian Treatments for COVID-19: SOLIDARITY,NA,2021,2022,University of British Columbia,39500,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",,2021 +C19549,202102VS1,COVID-19 Variant Supplement - Cellular Immuno-Therapy for COVID-19 Induced Acute Respiratory Distress Syndrome: the CIRCA-19 Trial,"The number of patients with the novel COVID-19 disease continues to rise world-wide. Approximately 20% of patients require hospitalization, and up to a quarter of these need intensive medical care, mainly due to intense inflammation (swelling) of the lung called 'acute respiratory distress syndrome' or ARDS. This interferes with the lung's ability to exchange oxygen, requiring a machine to support their breathing called a ventilator. Unfortunately, about half of patients who need a ventilator because of COVID-19 lung disease will not survive. We have no specific therapy to treat the lung swelling in these patients. Mesenchymal stromal cells, often termed 'MSCs', have anti-inflammatory effects that can reduce lung swelling in animal models of ARDS. As well, therapy with MSCs in humans has been shown to be safe, with some promising results in patients with severe inflammation due to uncontrolled infections as well as lung swelling due to ARDS. The few small clinical studies using MSCs to treat COVID-19 patients were not properly designed to assess the benefit of MSC therapy. The proposed Cellular Immuno-Therapy for COVID-19 related ARDS (CIRCA-19) trial is a randomized and placebo-controlled study designed to test whether giving MSCs to patients with severe lung swelling due to COVID-19 disease will decrease the need for a ventilator and whether this novel therapy will also have other important benefits such as improving survival and reducing the injury to vital organs like the heart, lungs and kidneys. The MSCs will be obtained from umbilical cords that are harvested during Caesarian section, and then grown in a specially equipped clinical-grade cell manufacturing facility at The Ottawa Hospital using Health Canada approved processes. We have rapidly deployed a multidisciplinary team and have already submitted the study to both Health Canada and Research Ethics for approvals, and we anticipate treating our first patient in early June 2020.",2021,2022,Ottawa Hospital Research Institute,39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Clinical trials for disease management,2021 +C19550,202102VS1,COVID-19 Variant Supplement - Characterization of Covid-19 infection in rheumatoid arthritis patients- the CoViD-in-RA project,"Rheumatoid arthritis is an incredibly diverse disease. The variability observed in clinical presentation, response to treatment and clinical outcomes suggest that the mechanisms activated during the initiation of the disease, are not uniform. Thus, RA offers a unique model to understand how different underlying immune abnormality lead to different outcome when infected with COVID-19. We aim to correlate clinical manifestations, response to treatment and laboratory parameters in order to inform clinical decisions in RA, especially during COVID-19 infection. Patients with recent arthritis will have blood tests (to analyze immune cells and proteins characteristic for RA subtypes) at baseline and at 6 months. Many patients followed in our service have already had these tests (EUPA cohort Dr Boire), and will also be included in our study, distinguishing between subjects who had COVID infection and those who did not develop it. All patients will have COVID-19 serologies and an analysis of their immune cells. This simple approach is original because we will study the different kinds of immune blood cells (not all cells mixed in whole blood) of patients before they have received any medication, as well as after initiating specific RA treatments. We will follow the patients when receiving DMARDs and advanced therapies prescribed to control their disease. We believe that RA heterogeneity could translate into a different susceptibility to the risk of having COVID-19 infection and to the severity of the infection, with a potentially protective effect from certain treatments in some patients. If we can determine which biological profiles or which treatments are associated with a good or bad response to SARS-CoV2, this could facilitate the management of individuals using these drugs for RA or other diseases, and perhaps also help target therapeutic interventions for COVID-19 in any person, affected with RA or not.",2021,2022,Université de Sherbrooke,39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Immunity | Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +C19551,202102VS1,COVID-19 Variant Supplement - Computer-aided discovery of synergistic drug combinations with Remdevisir for COVID-19 through mechanism-based drug repurposing and combinatorial organoid screening.,"With more than 4 million cases and over 300,000 deaths worldwide, it is critical to find an effective treatment against COVID-19 and to find it fast. Hopes for ending the pandemic largely rely on new vaccines, however the development of vaccines typically takes years and even if one is available today (which is not), its approval will take more than a year in the most optimistic scenario. Thus, the only realistic option for rapid COVID-19 treatment is drug repurposing. Drug reprofiling (repurposing) implies the use of existing drugs approved for other indications, and yet showing useful activity against SAR-CoV-2 virus. One well-known example of this strategy is remdesivir, currently the most promising treatment against COVID-19, and which was originally developed as Hepatitis C drug. Although very promising, remdesivir is still modestly efficient against COVID-19 and hence, if one could further boost its effectiveness by using it in a synergetic combination with another reprofiled drug, the pandemic might finally see the resolution. This consortium of national and international scientists wants to identify such much-needed SARS-CoV-2 inhibitor among known drugs, which then will be used either as stand-alone therapy for COVID-19 or a synergetic 'booster' for remdesivir. This team of scientists was recently awarded four COVID-19 rapid response grants to build a state-of-the-art organoid-based screening platforms established at UBC CL3 infectious disease facility, working in sync with high-resolution crystallography and artificial intelligence-enhanced molecular modeling and imaging platforms. We are ready and prepared to push forward this project even in this extremely condensed 1-year timeframe. The proposed research will generate high quality data on COVID-19 treatments shared through extensive international collaborations, will initiate critical clinical trials, and will position Canada as a world leader in the global fight against the pandemic.",2021,2022,University of British Columbia,39500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19552,202102VS1,"COVID-19 Variant Supplement - Contribution of genetic variation of ACE2, the receptor for SARS-CoV-2, to COVID-19 disease expression and development of therapeutics","The coronavirus causing the COVID-19 pandemic infects by binding to a receptor called ACE2 on the surface of cells lining the lung. One reason for the virulence of this new virus is the strength of its binding to ACE2. However, one of the leading mysteries of the outbreak has been the wide range of responses to infection, from a complete absence of disease in some, to life-threatening pneumonia in others. Regional difference across the world in disease expression have also been reported, as has a striking increased severity of COVID-19 in men compared to women. Here, we propose to investigate whether genetic variation in the human ACE2 receptor protein underlies these differences. We will test this by making all possible mutations in the ACE2 gene and testing impact on binding to the viral protein. Results from our study will have important impact on new development of therapeutics by improving computational models of ACE2-virus interactions used to design drugs blocking this binding. Another important outcome from our study would be the identification of genetic variants of ACE2 with heightened binding affinity for the viral protein. Such variants can be used as novel therapeutics by out competing virus in a patient's system, preventing virus from infecting host cells. Critically, once established, our platform will be highly versatile and readily allow testing new strains of the COVID-19 virus for increased or decreased infectivity. This platform will also be invaluable to provide a more rapid response to any new virus that appears in the future that infects cells by binding the ACE2 receptor.",2021,2022,University of British Columbia,39500,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C19553,202102VS1,COVID-19 Variant Supplement - CovidFree@Home: Development and validation of a multivariable prediction model of deterioration in patients diagnosed with COVID-19 who are managing at home,"Millions of Canadians are anticipated to be infected with COVID-19 during this pandemic and many more will contract it in ongoing community transmission and/or a possible second wave. The majority of people who test positive for COVID-19 are sent home to isolate. In this population, deterioration of their disease can happen quickly and without warning, and we currently cannot accurately predict the approximately 20% who deteriorate and need hospitalization. From discussions with our patients and patient advisor, we know that people who are isolating at home feel terrified and alone. We need an effective and safe ambulatory care and research strategy for people with COVID-19 isolating at home. We are a team of heath care workers, patients, researchers and computer scientists (WearCOPD.ca; Can-BREATHE.ca) with five years of experience developing and using remote monitoring systems for respiratory disease. We have already built a smartphone application to facilitate the care of people with COVID-19 at home by allowing them to report their symptoms to their physician. With this project, we will expand our system to also include continuous smartwatch-based monitoring of heart rate, respiratory rate, cough, speech and other parameters. Sensor data will provide us with large volumes of objective data and allow us to build accurate real time machine learning models for predicting who needs to go to hospital. We will integrate these models into a dashboard that alerts clinicians of any patients that area getting worse, so that they can be called into hospital. Patients can be reassured that they are being followed thoroughly even though they are at home. Our system will also provide a platform for further research into how to prevent long term sequalae and preserve the health of people with COVID-19 who do not require hospitalization.",2021,2022,"Sunnybrook Research Institute (Toronto, Ontario)",39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Disease pathogenesis | Supportive care, processes of care and management | Health service delivery",2021 +C19554,202102VS1,COVID-19 Variant Supplement - Design and evaluation of novel inhibitors targeting SARS-CoV-2 polymerase to create lead compounds to develop more effective treatments of COVID-19,"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 produces a key enzyme, nsp12, essential for replicating the viral genome. In combination with the sequence of nsp12 from SARS-CoV-2, previous studies on closely related enzymes from other viruses provide insights into how nsp12 functions. Our analysis indicates how the specific structural features of nsp12 provide new opportunities for creating inhibitors with higher activity and specificity, and thus likely to act as more effective medications for treating COVID-19. Our models of the 3D structures of nsp12 bound to RNA and drugs like remdesivir indicate how existing inhibitor compounds developed to treat other viral diseases could be modified to work more effectively for treating COVID-19. We propose to synthesize a series of modified inhibitors tailored to fit the structure of nsp12 and then test the activity of these inhibitors on purified nsp12 using a previously published assay procedure. The ability of different inhibitors to disrupt the activity of nsp12 will be measured using this assay. The most effective inhibitors will be cocrystallized into a hybrid form of the norovirus polymerase to provide timely structural information about how inhibitors are likely to bind to nsp12. This structural information will help to further refine the design and improvement of the next generation of inhibitors. Promising inhibitors will be passed on to collaborators and the general community to evaluate their effectiveness in cell culture infection models and ultimately in human clinical trials. We expect to synthesize the first series of novel inhibitors within 4-6 months and to be able to evaluate their activity by the end of 2020. Additional structural characterization will take another 4-6 months. Based on this information, a second generation of inhibitors will be prepared and characterized by the end of the 2-year project.",2021,2022,University of Calgary,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19555,202102VS1,COVID-19 Variant Supplement - Development and implementation of rapid metagenomic sequencing coupled with isothermal amplification point of care testing for viral diagnostics,"Infectious pandemics or plagues have altered human history since the beginning of time. Today we face the threat of viral pandemics spreading through human populations disseminated fueled by the ease of international travel which has become commonplace. SARS, influenza, and now the 2109 novel coronavirus are examples of just a few of these pandemics. We must create novel tools that enable us to rapidly identify the virus and then develop a test that can reliably test for the virus in patients. The test has to be portable and taken to the bedside where patients are quarantined so that these individuals do not further transmit viruses in our hospitals and public places.",2021,2022,University of Calgary,39500,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19556,202102VS1,COVID-19 Variant Supplement - Development of a Microwave Enabled Bio-Nano-Microfluidic Device for Point-of-Care Diagnosis of COVID-19,"The COVID-19 crisis has caused over 280k deaths with more than 4 million infections as of May 8, 2020. These numbers are increasing and may peak again with reopening of businesses. This tragedy could be prevented from happening or its impact could be largely minimized if rapid, massive-scale testing can be performed at community level without the need of highly trained professionals and expensive equipment. This is also the highly recommended action among the immediate next steps by World Health Organization (WHO). The proposed project aims to develop such a system for rapid point-of-care (POC) diagnosis of the COVID-19 virus by leveraging the team's expertise in engineering, nanotechnology, viral immunology and clinical medicine. The proposed system is a palm-sized instrument that consists of a battery-powered microwave circuitry and a microwave-microfluidic device with its sensor surface modified by functionalized gold nanoparticles (gNPs) that specifically recognize the COVID-19 virus. The output is a yes/no answer via a light indicator. A test can be done within 30 minutes including the sample preparation, which is completed by simply stirring a nasopharyngeal swab containing a tested person's sample in a buffer solution. The system allows a test to be completed with a small drop of the sample solution (5 microliter) that is filled in the inlet reservoir and drawn to pass the detection chamber towards the outlet by capillary force. If the sample contains the COVID-19 virus, the virus will be captured by the functionalized gNPs coated on the sensor surface resulting in the change in the microwave spectrum. The microwave circuitry will analyze the spectrum and output a yes/no answer. It is expected that the availability of the proposed portable system will enable the test of COVID-19 at the community level such as at a drive-through point or in an ambulance, which will largely expand the testing capacity and thus assist in the control the COVID-19 pandemic.",2021,2022,University of Waterloo (Ontario),39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19557,202102VS1,COVID-19 Variant Supplement - Development of a nanoparticle-based vaccine candidate to the SARS-CoV-2,"The recent outbreak of the coronavirus in the province of Wuhan in China is an international concern since there is a risk for spreading the infection outside the Chinese territory. The spreading of the virus is facilitated by its human to human transmission by aerosols. Several approaches must be taken to limit the spread of the virus, including quarantine, the decontamination of infected areas, early detection in patients, etc. It is also widely recognized that vaccination is from far the most efficient approach to control the spreading of the infection and protect the population. We propose first the development of a vaccine component-1 to the SARS-CoV-2 based on the use of an immune enhancer nanoparticle coupled to peptides derived from the virus nucleocapsid. This vaccine will trigger a protective immune response against the virus. The use of peptide antigens allows moving very fast in the development of the vaccine candidate. Besides the speed, this approach has the merit to induce a broad CTL immune response that should also trigger protection to any strains of the virus that are related to the Wuhan virus, like the SARS virus of 2002. Second, we will design and prepare a second vaccine component that will elicit the production of neutralizing antibodies to the SARS-CoV-2. Finally, both components will be combined in one vaccine formulation that will provide robust protection to the SARS-CoV-2 and also to related viruses, like the SRAS virus of 2002. The nanoparticles used to attach the vaccine antigens are very stable. The coupling to the nanoparticle will stabilize the antigens and generate a very stable vaccine formulation that can be stockpiled for a long period (years) without loss of integrity. This is an advantage because to insure preparedness to other epidemics with related viruses.",2021,2022,Université Laval,39500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C19558,202102VS1,COVID-19 Variant Supplement - Development of a novel DC-targeting vaccine that targets COVID-19 spike protein to control COVID-19 infection,"COVID-19 is a coronavirus identified as the cause of an outbreak of respiratory illness that was first detected in Wuhan, China. There is currently no vaccine to prevent COVID-19 infection. The spike protein (SP) of the virus is the key molecule for entry into a cell and is a main target of host protective immune responses. A receptor-binding domain (RBD) located in SP is essential for the infection of COVID-19. Previous studies have demonstrated that RBD of SARS-CoV consists of multiple neutralizing epitopes that induce highly potent neutralizing antibodies. The neutralizing antibody can bind to SARS-CoV and interferes with its ability to infect a cell. These findings suggest that RBD of COVID-19 is an ideal anti-COVID-19 vaccine candidate. Dendritic cells (DCs) are antigen-presenting cells that play critical roles to efficiently present viral antigens to the T cells of the immune system. Therefore, targeting DCs is a promising strategy to improve vaccine effectiveness. Recently, we have developed a highly efficient DC-targeted vaccination technology, and in this study, we will use this vaccination technology to expose the RBD of COVID-19 to host immune system. We will also investigate the potential of this novel vaccine approach to elicit potent immune responses against COVID-19 and SARS-CoV infections in vivo. The success of this proposed study will lay the groundwork for the quick development and production of anti-COVID-19 vaccine candidates, and contribute to a rapid response towards controlling the COVID-19 pandemic in China and worldwide",2021,2022,University of Manitoba,39500,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2021 +C19559,202102VS1,COVID-19 Variant Supplement - Development of a portable point-of-care device for rapid testing of SARS-CoV-2,"The novel coronavirus (SARS-CoV-2) outbreak that started in December 2019 triggered unprecedented measures to avoid a global pandemic. However, China has been particularly hit with over 70 000 confirmed cases, of which about 80% are in Hubei province. Wuhan, capital city of Hubei, is considered ground zero of the outbreak. Testing is typically performed at centralized facilities with highly qualified personnel operating specialized equipment, RT-qPCR being the current method of choice and DNA sequencing a second choice. The response time between sampling patients and obtaining clinically relevant information usually depends on sample shipping time and clinical lab capacity. In this current outbreak containment situation in China, large portions of the population are quarantined, travel is restricted, and clinical labs are operating well over capacity. We propose to develop a rapid point-of-care test to help mitigate the outbreak of COVID-19. The RNA-based test will be performed with a high sensitivity, label-free sensing method. RNA purification and amplification will not be required. The instrumentation needed will be portable and lightweight to enable frontline workers to rapidly test for SARS-CoV-2. The assay will be developed with an easy-to-use platform that can be operated by untrained personnel. It can thereby be deployed locally, within regions of quarantine at a temporary health centers and neighbourhood clinics, reducing flow of people in urban centers; it can be shipped and used in remote or isolated areas including cruise ships",2021,2022,Université Laval,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19560,202102VS1,COVID-19 Variant Supplement - Development of a rapid point-of-care diagnostic test for COVID-19,"A novel zoonotic coronavirus (SARS-CoV-2) has recently been identified in patients with an acute and potentially fatal respiratory disease (COVID-19). This virus is genetically similar to SARS and MERS coronaviruses. The outbreak started in the city of Wuhan (China) and then soon turned into a pandemic with over 60,000 clinical cases and at least 1,500 fatalities. Cases in healthcare workers and other close contacts indicate human-to-human transmission. Rapid, simple and specific point-of-care diagnostic tests are urgently needed for the quick isolation of those infected. To address the issue, we have assembled a team of specialists in chemistry, infectious diseases, and clinical diagnostics. We propose to develop rapid point-of-care tests based on aptamer-assisted graphene oxide (AptaGO) and paper enzyme-linked aptamer assays (p-ELAA) for SARS-CoV-2 and its surrogate (HCoV-229E), which is a Containment Level 2 (CL-2) pathogen. The aptamer-based sensors can rapidly (",2021,2022,University of Ottawa,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19561,202102VS1,COVID-19 Variant Supplement - Development of COVID-2019 main protease inhibitors as potential antivirals against the 2019 coronavirus.,"Coronaviruses are associated with a variety of human diseases ranging from the common cold to new and serious conditions such as Severe Acute Respiratory Syndrome (SARS), which emerged in 2002, Middle Eastern Respiratory Syndrome (MERS), first reported in 2012, and a recent and still growing outbreak of COVID-19, caused by the coronavirus SARS-CoV-2. MERS and SARS together claimed over 1600 lives, and the death toll of COVID-19 recently passed 1300 and is growing rapidly. It is currently unclear if the COVID-19 outbreak can be contained, with some estimates of potential fatalities reaching as high as 50 million. There is currently no approved treatment for any coronavirus, although clinical trials of the Gilead compound Remdesivir are currently underway and there is some optimism that it may be effective against SARS-CoV-2. Nevertheless, there is an urgent need for additional potential SARS-CoV-2 therapeutics, as the success of Remdesivir is far from assured. We are proposing to use a combination of computer calculations and laboratory testing to rapidly identify and validate molecules that block an enzyme that is essential to the virus. The targeted enzyme, known as 3CLpro, is responsible for processing viral proteins into their active forms. A detailed 3D structure of the SARS-CoV-2 3CLpro enzyme was recently solved, and this provides enough information to identify chemical structures of molecules that are likely to block its action, through a procedure known as virtual screening. We will synthesize promising compounds and test them against the purified enzyme using a technique known as Isothermal Titration Calorimetry (ITC). Our team has a proven track record of using virtual screening and ITC to generate potent inhibitors of enzymes similar to 3CLpro. Molecules we identify are likely to prevent the virus from replicating and would have high value as new potential treatments for COVID-19 that could be used alone or in combination with other therapies",2021,2022,McGill University,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19562,202102VS1,COVID-19 Variant Supplement - Development of safe and effective vaccines against COVID-19,"The current COVID-19 pandemic is a worldwide threat. Moreover, the ability of asymptomatic carriers to transmit the disease is making it very difficult to contain and control. As such, safe and effective vaccines against COVID-19 are urgently needed. The goal of this research project is to develop effective vaccines to combat COVID-19. Combining our expertise in coronaviruses, vaccine development and viral vector engineering, we plan to take novel approaches to develop highly effective vaccines against COVID-19. We will use a helper-dependent adenoviral (HD-Ad) vector to deliver antigens and we will also generate a bacterium-based BCG-COVID-19 compound vaccine. The HD-Ad vectors that we will use offer several advantages over the conventional Ad vectors: 1) they are safer for human use and potent in the delivery of specific antigens, 2) they have a large DNA carrying capacity for expressing multiple antigen genes without the expression of non-specific antigens from the vector and 3) they produce antigens in their native folded form with proper glycosylation and may not require boosting. BCG is an attenuated bacterium and the approved vaccine against tuberculosis in humans. In addition to its specific immune protection against TB, BCG has non-specific benefits as it prevents about 30% of infections with pathogens including viruses. We will construct a recombinant BCG that secretes a fusion protein composed of the bacterial protein antigen 85A fused to the SARS-CoV-2 RBD. This recombinant vaccine will not only retain BCG's nonspecific anti-viral benefits but will also produce specific immune protection against COVID-19. The success of this project will allow us to proceed with the production of the clinical grade vaccines for further testing clinically more than one vaccines while establishing a collaboration with a Canadian biotech that can oversee the licensing and large-scale production of this vaccine for the Canadian market.",2021,2022,University of Toronto,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C19563,202102VS1,COVID-19 Variant Supplement - Development of SARS-CoV-2 Peptide Therapeutics and Point-of-Care Salivary Diagnostics for Rapid Viral Detection,"SARS-CoV-2 (the causative agent of COVID-19) poses a generational threat, with no licensed vaccines or effective therapies to date. Further, the scarcity in reliable diagnostics, especially when testing asymptomatic/mildly symptomatic cases, is of grave concern. Accordingly, our proposal tackles 2 of the 3 research areas of this call, and addresses all 5 objectives, by developing and testing SARS-CoV-2 therapeutics and also prototyping convenient point-of-care (POC) COVID-19 diagnostics with scaling-up feasibility. For the therapeutic arm, we will innovatively design and test peptide disruptors of the SARS-CoV-2 spike (S) glycoprotein interaction with the human ACE2 receptor during viral entry, and other peptide inhibitors of viral-human interactions required for SARS-CoV-2 establishment. These will be tested in vitro using cell-based assays, with promising disruptors validated in SARS-CoV-2 hamster models. In addition, we will screen our in-house synthetic compounds targeting chaperones as potential SARS-CoV-2 replication inhibitors in both cell-based assays and animal models. On the diagnostic front, we will develop new diagnostic solutions for effective detection of even mild/asymptomatic SARS-CoV-2 carriers at home and/or in remote locations. This POC lab-on-a tip technology will specifically detect SARS-CoV-2 peptides from patient saliva, with our clinician collaborators taking the lead in scaling-up both peptide therapeutics and our POC diagnostic device through ongoing coordination with the federal government and Saskatchewan Health Authority. This proposal brings together leading Canadian scientists and clinicians to fulfill our objectives by generating high-quality data to diagnostically and therapeutically accelerate the detection and prevention of COVID-19 and foster nationwide collaborations, with a clear scaling-up path that will refine decision-making across Canadian jurisdictions for effective and timely containment of the COVID-19 outbreak.",2021,2022,University of Regina (Saskatchewan),39500,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2021 +C19564,202102VS1,COVID-19 Variant Supplement - Development of small interfering RNAs (siRNAs) for the treatment of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2),"SARS-CoV-2 is responsible for the current coronavirus disease 2019 (COVID-19) pandemic for which there are no treatments yet available. We propose to rapidly design and test several drugs that could be delivered intranasally to treat SARS-CoV-2. We will also analyze the immune response to the virus in patient cells to determine a possible correlation between the early response and the outcome of the disease. The technology we will use is called RNA interference and it works by using what are called small interfering RNAs (siRNAs). siRNAs can direct a person's existing RNA interference machinery to attack any harmful RNA sequence such as the RNA genome of SARS-CoV-2. Furthermore, by reducing the viral burden, siRNAs could contribute to mounting a patient's natural immune response to the virus. We will also design siRNAs to target any factor that would prevent the immune response in the early phase of the disease. siRNAs are easy to design, manufacture and are stable for long-term storage and transport. An advantage for their use as therapy for respiratory infections is that they remain in the lungs when administered intranasally and therefore have low potential to cause side-effects in other parts of the body. We expect that from our project we will identify a safe and effective treatment that could be used in the fight against the current pandemic and future outbreaks of related coronaviruses.",2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +C19565,202102VS1,"COVID-19 Variant Supplement - Development of vaccine candidates and monoclonal antibodies to interrupt the spread of the novel coronavirus, COVID-19.","The novel coronavirus (Covid19) that emerged in Wuhan, China is a threat to global health. Infection causes respiratory disease that can progress to pneumonia, acute respiratory distress and even death. Often patients require hospitalization and intensive care, which increases the chance of viral spread within health care settings. Since it was first identified there have been over 69000 cases, and 1600 deaths, and the virus has spread to multiple countries. Currently, there are no vaccines or therapeutics, but these are urgently needed to bring the epidemic under control. Our proposal seeks to address these areas of need by a multifaceted approach. Specifically, the objectives of this proposal include: 1) Isolation of virus and generation of an in vitro reverse-genetics COVID-19 system 2) Identification of neutralizing antibodies 3) Development and evaluation of candidate vaccines Additionally, the project will generate data on the safety of candidate vaccines in humans through a phase I trial. This will help determine which vaccines can be advance for further study. This will be accomplished through synergistic research between the biotechnology companies Medicago and Inovio in conjunction with several academic research laboratories. Dr. Kobinger's group has an established track record of translational research, and has successfully brought a DNA-vaccine against MERS-CoV to phase I clinical trials 24 months after commencing the project and in less than 7 months for Zika virus. He has led multinational collaborations in the past, and has a history of promoting collaborative and transparent consortium-based research programs. This proposal will develop tools that can be shared with the world scientific community that will help further our understanding of viral pathogenesis, transmission as well as screen potential small-molecule inhibitors and antibodies. Collectively, the findings from this project have potential to contribute to global response against COVID19.",2021,2022,Université Laval,35123.4,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C19566,202102VS1,COVID-19 Variant Supplement - Development of Vaccines to Prevent SARS-CoV-2 Infection of High Risk Individuals,"The physical-distancing strategy currently implemented in the Covid-19 pandemic in Canada has been very effective in preventing the vast majority of Canadians from being infected by SARS-CoV-2. This essential short-term strategy is saving lives, but paradoxically will leave most of our citizens without protective immunity and a recurrent outbreak is both predictable and likely without an effective Canadian vaccine strategy. A global effort has been initiated to identify an effective Covid-19 vaccine, testing a variety of vaccine platforms and strategies. Unfortunately, few of these are being developed, tested or manufactured in Canada leaving our population in a very perilous situation where our vaccine needs could be de-prioritized by foreign governments. This project is aimed at bringing together a multi-disciplinary team of scientists and clinicians to rapidly create and manufacture a vaccine to prevent a second wave of infections. We are using scientists and infrastructure, already available in Ottawa, Montreal, Calgary and the US (Covington Louisiana) to rapidly create, compare and contrast different vaccine strategies in animal models. Our best candidate will then be manufactured in a pure enough form to inject in humans. We will complete all of the data and regulatory documents to prepare an application to Health Canada to allow the initiation of a clinical trial in healthy volunteers.",2021,2022,Ottawa Hospital Research Institute,39500,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies | Clinical trial (unspecified trial phase),2021 +C19567,202102VS1,COVID-19 Variant Supplement - Drug repurposing for the rapid development and evaluation of SARS-CoV-2 antivirals,"The initial symptoms of COVID-19 are fever, shortness of breath and a dry cough. For some patients, the disease progresses to pneumonia as the infection spreads to the lung and leads severe inflammation. These severe symptoms can cause difficulties for the lungs to oxygenate the blood and can lead to death. There are currently no antivirals against SARS-CoV2, the causative agent of COVID-19, and development of new molecules can take years to reach patients. As the COVID-19 epidemic is progressing rapidly, the need for antiviral therapy is urgent. Therefore, our goal is to use our current arsenal of approved drugs already tested for their safety and used in the clinic for various conditions and repurpose them to treat COVID-19. In this rapid response grant, we propose to identify drugs with activity against SARS-CoV2 in vitro and in vivo and contribute to the global COVID-19 response and provide a therapeutic option for patients developing life-threatening disease.",2021,2022,University of Ottawa,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19568,202102VS1,COVID-19 Variant Supplement - Early immune predictors of sustained SARS-CoV-2 antibody responses after COVID-19 disease,"COVID-19, a disease caused by a new Coronavirus, is an unprecedented global health crisis for which we currently have nor safe nor rapid response. Given the absence of vaccines and effective therapies, it is essential to understand the development, effectiveness and maintenance of antiviral responses against its causing agent, the SARS-CoV-2 virus. The highly variable immune response against SARS-CoV-2 define the severity of the disease, but many critical questions remain: 1) can we predict patients that will experience a severe disease and delayed viral clearance? 2) do survivors of COVID-19 develop durable and protective antiviral immunity? 3) can serology identify convalescent COVID-19 patients who are at high risk of re-infection? 4) does re-exposure to the virus boost their antiviral immunity? We propose the creation of a multi-site consortium composed of 12 scientists (6 women and 6 men) with solid expertise in virology and immunology and from leading academic institutions in Quebec (UdeM, IRCM) and the US (Columbia, NY) to study antiviral immunity in COVID-19 in both sexes to address unresolved issues, as outlined in the CIHR call: in Aim 1 and 2, we focus on early clinical and immunological features of COVID-19 that can predict the emergence of protective and durable antibodies. We will compare cohorts of patients enrolled in the ""Biobanque quebecoise de la COVID-19"" (BQC19) that experienced mild or severe COVID-19 or COVID-19-like symptoms attributed to another infectious agent. In Aim 3, we will focus on a cohort of health care worker tending COVID-19 patients, therefore at higher risk of repeat exposure to the virus. Using this cohort, we will study the effect of repeat exposure on immunity boosting against the virus and help define the immunological requirements of a successful vaccine. Taken together, our proposal will provide the immunological perspective needed to better prepare and implement a safe exit from the current public health crisis.",2021,2022,Centre hospitalier de l'Université de Montréal (CHUM),39500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2021 +C19569,202102VS1,"COVID-19 Variant Supplement - Engage-COVID-19: A mixed methods study of biomedical, behavioural, and psychosocial aspects of the COVID-19 pandemic among gay, bisexual, and other men who have sex with men in Canada","Gay, bisexual, and other men who have sex with men (GBM) have historically experienced significant disparities in physical, mental, and sexual health, amplified by systemic marginalization and high barriers to healthcare. This context of inequity creates heightened vulnerabilities to COVID-19. Failure to respond to the health and wellness needs of GBM may have significant negative effects on COVID-19 outcomes and exacerbate existing health disparities. We propose the Engage-COVID-19 Study to rapidly respond to current and pressing knowledge gaps concerning the COVID-19 pandemic among GBM in Canada. This study will be embedded within the Engage Cohort Study, which is the only study with comparable biobehavioural data on HIV/STI prevalence and risk behaviours for GBM in Canada. To date, baseline data collection has been completed with 1842 GBM who are enrolled in the Engage Cohort Study (565 in Vancouver, 388 in Toronto, and 889 in Montreal). All of these participants will be invited to have SARS-CoV-2 antibody testing and complete an in-depth survey that will include COVID-specific quantitative questions. We anticipate recruiting a total sample of 1695-1768 participants. In addition, from this group we will recruit 90 GBM participants for qualitative interviews in Vancouver (30), Toronto (30), and Montreal (30) to assess the direct and indirect impacts of COVID-19 on Canadian GBM. These data are necessary both to understand COVID-19 risks, vulnerabilities, and prevention strategies, as well as the impacts of COVID-19 on health service access and different levels of HIV/STI risk across provinces. By making efficient use of available research infrastructure, our proposed study will ascertain the occurrence of COVID-19 by documenting SARS-CoV-2 immunity within both HIV-positive and -negative participants and produce rapid, high-quality evidence for preventing the direct and indirect effects of COVID-19 for this population across multiple jurisdictions.",2021,2022,University of Toronto,39500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts,2021 +C19570,202102VS1,"COVID-19 Variant Supplement - Evaluating the differential impact of what we have done, as we prioritize what to do next: a multi-provincial intervention modeling study using population-based data","In Canada, as elsewhere, the COVID-19 epidemic has spread at varying speeds and amplitudes across people, places, and time. Early model predictions were dire across the board largely because of limited local data. So early models had to assume that we were all at equal risk, regardless of conditions that can lead to differential risks of transmission (e.g. living in shelters or long-term care facilities) and of severe outcomes (e.g. age, health conditions). Thus, an assumption of homogeneity was at the heart of the ""hammer"" part of the public health response. Public health measures (interventions) also varied between provinces. As we enter the ""dance"" phase and prepare for future waves of the epidemic, we have an opportunity to be more specific with our interventions if we can quickly learn from how well our public health measures worked or did not work for different subgroups and between provinces, using the wealth of data now available. Our team will use an integrated surveillance and health-administrative data infrastructure and mathematical models that were built over the last 2 months in Quebec, Ontario, Manitoba, Alberta, and British Columbia to answer the following questions: 1. Who, where, when, and under what conditions are subsets of the population most at risk? 2. What led to differences in the trajectory and size of COVID-19 sub-epidemics within and between provinces? 3. What types of population- and facility-specific strategies that could stop these sub-epidemics and prevent their re-emergence, while allowing us to relax universal physical distancing measures? Our team of epidemiologists, mathematical modelers, statisticians, clinicians, microbiologists, and public health officials will work together to rapidly provide answers in way that embraces data-driven heterogeneity in risks so that we can better inform decisions on what to implement, when, for whom, and for how long, to minimize the need for universal stay-at-home strategies.",2021,2022,Unity Health Toronto,39500,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management | Infection prevention and control,Disease susceptibility | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Restriction measures to prevent secondary transmission in communities,2021 +C19571,202102VS1,COVID-19 Variant Supplement - Expression and Purification of COVID19 Virus Spike (S) Protein for Diagnostics and Vaccines,"Projects described within this rapid response proposal relate to diagnostics and vaccine production. The reagents generated also have longer term ramifications for studying virus attachment and developing inhibitors that block host cell entry and virus mediated fusion. The work in this proposal focuses on the spike protein (S) of the coronavirus which mediates attachment and entry into the host cell and is the major target of neutralizing antibodies that block infections. The first goal of this proposal is to generate large quantities of the S protein is a mammalian expression system that can be easily scaled up for large scale production. The protein generated in this procedure can be used to produce immune diagnostic kits as well as serve as a component of subunit vaccines or booster shots directed against COVID-19. The second aim describes the generation of recombinant vesicular stomatitis (VSV) viruses that express the Spike (S) protein derived from COVID-19 virus. In the first experiments, VSV genome vector is modified to contain coronavirus S protein in place of its G glycoprotein which normally mediates attachment and entry of the host cell. The S protein changes the tropism of the recombinant virus and provides a new antigen target for the immune system. VSV is highly attenuated in human cells and is tightly controlled by the host antiviral interferon system. It is also the vaccine vector for the highly effective Ebola virus vaccine. The diagnostic and vaccine reagents developed in this proposal will be distributed and tested by colleagues at the Canadian Center of Vaccinology (Halifax) and VIDO-InterVac Vaccine Cenre in Saskatoon. The final aim of this proposal will use the reagents generated in the proposal to study cell receptors for COVID19 coronavirus and study infections in susceptible cells using model viruses of lower risk and pathogenicity.",2021,2022,Dalhousie University (Nova Scotia),39500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C19572,202102VS1,COVID-19 Variant Supplement - Genomic epidemiology and evolutionary dynamics of COVID-19 and other emerging corona viruses,"Emergence of the 2019 coronavirus (SARS-CoV-2) has highlighted the severe impact emerging zoonotic pathogens have on human health, the global economy, and health service delivery. Phylogenetic analyses of SARS-CoV-2 genomic sequences improve our understanding of host reservoir species, assess the potential for transmission to humans, and illuminate evolutionary dynamics relative to other viruses in Coronaviridae, informing response to current and future epidemics. We will study the genomic evolution of SARS-CoV-2 to investigate if particular motifs are under selection for increased virulence and immune evasion. We will compare SARS-CoV-2 with genomes of other zoonotic coronaviruses to elucidate common genomic features associated with virulence, host switching, and human-to-human transmission. We will also evaluate spatiotemporal transmission patterns of SARS-CoV-2 across different populations using Bayesian phylogeographic analyses. Such analyses allow identification of spatially and temporally structured, clinical and epidemiological parameters such as the basic reproduction number, period of infectiousness, and true viral prevalence over time within different populations. We will also elucidate the reservoir host species of SARS-CoV-2 in concert with collaborators from the Chinese Centre for Disease Control as well as other Canadian researchers by probing unique environmental samples as well as both novel and existing datasets available for coronaviruses. Phylogenetic co-speciation analysis will explore whether coronaviruses are more likely to jump between phylogenetically proximate host species allowing development of a predictive framework to anticipate future zoonotic events. We will identify genomic factors of SARS-CoV-2 associated with virulence, estimate vital epidemiological parameters, and illuminate potential reservoir species. With the Chinese CDC, we will help focus the response, control and elimination of the current, and future, coronavirus outbreaks.",2021,2022,University of British Columbia,39500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2021 +C19573,202102VS1,"COVID-19 Variant Supplement - Gig couriers delivering people, food and packages in a pandemic: Containment strategies to mitigate the occupational and public health impact","Gig courier workers, such as Uber Eats, Amazon Flex, and Lyft drivers, have been busier than ever during the Canadian COVID-19 pandemic as the public attempts to avoid illness by ordering take-away food, shopping online and taking ride-hails rather than public transportation. This places gig courier workers in a unique position to become infected with COVID-19 and transmit it to others as they move people, food and packages from one location to another. Although gig couriers are key vectors between where people live (e.g. homes, care facilities) and the outside world, formal strategies do not exist to protect them from exposure and to mitigate their role in disease transmission. Importantly, this risk is not expected to change anytime soon as the high use of couriers will likely not decline as the economy re-opens. This study will contribute to coronavirus containment strategies by identifying disease transmission risks embedded in gig work contexts and practices, developing clear and tailored interventions for gig courier workers about gig courier disease-related safety and transmission, and widely disseminating results, in live time, as they are identified. Using framework analysis explicitly geared towards generating policy- and practice-orientated findings within limited time periods, we will: document existing courier safety organisational policy; map gig courier worker work, disease exposure and transmission conditions (with attention to gendered dimensions) via social media forums and in-depth interviews with workers and courier firm representatives; and categorise disease transmission risks. Supported by our Strategic Advisory Committee of unions, government municipalities, employers, and vulnerable worker advocates, and using real-time public health communications, this study will create effective national interventions to reduce gig courier disease exposure and protect the public health of Canadians using these courier services.",2021,2022,University of Waterloo (Ontario),39427.32,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2021 +C19574,202102VS1,COVID-19 Variant Supplement - Host cellular protein substrates of SARS-CoV-2 proteases,"The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to COVID-19 disease in China and worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Currently, the pathogenic mechanisms that lead to COVID-19 and related SARS/MERS-CoV diseases are not understood. In this study, we will identify the host proteins that are targeted by a viral protein called a protease using an unbiased proteomics approach. Identifying the protein targets of SARS/MERS-CoV proteases will reveal into the protein sequence that binds to the proteases. We will engineer and optimize decoy protein sequences that will effectively block SARS/MERS-CoV protease function and thus, inhibit SARS/MERS-CoV infection. Uncovering the proteins that are targeted by the SARS/MERS-CoV proteases will also provide a catalog of the host processes that these viruses affect, thus gaining insights into the pathogenic mechanisms that lead to COVID-19 disease.",2021,2022,University of British Columbia,39500,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C19575,202102VS1,COVID-19 Variant Supplement - Household Transmission Dynamics and Vial Load among Asymptomatic SARS-CoV-2 Infected Children,"Children have milder disease than adults and many have no symptoms even when infected by SARS-CoV-2. At present, we do not know how likely asymptomatic-infected children are to transmit the infection. Gaining an understanding of this issue is crucial to determining the role children play in transmission and what the risks will be to other children and adults when children return to school. To answer these questions we will enroll children who are brought for care due to non-infectious reasons (e.g. fall, cut, injury, pain) to 20 emergency departments across Canada and the United States. These sites are participating in the CIHR-funded, 57-site, Pediatric Emergency Research Network (PERN)-COVID-19 study, and currently perform screening of select asymptomatic children for SARS-CoV-2. Participating sites will enroll 400 asymptomatic SARS-CoV-2 positive children and 1,200 uninfected children (3:1 ratio of uninfected to infected child). Study aims: 1) Household Transmission Dynamics: Data will be collected regarding exposures and symptoms at baseline and again at 14 days for enrolled children (infected and uninfected) and their household members. Household members who develop symptoms of COVID-19 will be encouraged to have SARS-CoV-2 testing done (if not already) and the results will be obtained. Analyzing and modeling this information, comparing households with transmission versus those without, will help us understand the transmission risk posed by asymptomatic SARS-CoV-2 infected children. In particular this information will inform social distancing policies (e.g. school re-opening) 2) Viral Load Quantification: All SARS-CoV-2 positive specimens will have viral load quantification performed. These results will be analyzed alongside those from aim #1 to determine the relationship with household transmission. Viral load quantification data will also be analyzed alongside symptom evolution data to inform our understanding of the presymptomatic state.",2021,2022,University of Calgary,39446.28,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | United States of America,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures,2021 +C19576,202102VS1,COVID-19 Variant Supplement - Implementation of serological and molecular tools to inform COVID-19 patient management,"Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a novel virus that causes COronaVIrus Disease 2019 (COVID-19). There is considerable variability in symptom severity and outcomes among patients infected by SARS-CoV-2. Linking genome and viral sequencing information to antibody (immune) response and other biological information (sex, age, ancestry, symptom severity, comorbidities, and outcome) may identify characteristics of patients that are associated with poor and favourable outcomes. This study will address three aims. Aim 1: Identify the characteristics of the antibody response that result in maintained immune response and better patient outcomes. Aim 2: Determine impact of genetic differences on COVID-19 infection severity and immune response. Aim 3: Determine impact of different viral strains on antibody response and patient outcomes. Patients with COVID-19 will be recruited from Sinai Health System, University Health Network, Baycrest Health Sciences and William Osler Hospital System. Patients seen in the emergency department with mild symptoms as well as hospital in-patients with more severe symptoms will be consented. Blood samples will be collected when patients are in hospital and 6 months and 1 year after COVID-19 diagnosis. Neutralizing antibody levels will be measured at all time points. Patient and viral genomes will be sequenced. Statistical analysis will be used to test for associations between antibody levels, genetic variation, viral genome variation, and patients' characteristics including age, sex, ancestry, comorbidities, and symptom severity. This study will link serological, genomic and patient characteristics to provide a comprehensive understanding of factors that contribute to variability in clinical symptoms and outcomes among COVID-19 patients. Evidence from this study will determine if immune response, viral strain and genome sequencing are effective for the diagnosis, prognosis and management of patients with COVID-19.",2021,2022,Sinai Health System (Toronto),39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2021 +C19577,202102VS1,COVID-19 Variant Supplement - Improving Outcomes in Individuals with COVID-19 with Renin-Angiotensin System Inhibition: The COVID-RASi Trial,"Cardiovascular disease is not only the #1 killer chronically, but is also the #1 killer in COVID-19. Elderly patients with previous heart attack or stroke, or hypertension or diabetes, have high risk of getting infected. Surprisingly they also suffer 3 to 5 times the chance of dying compared to other infected patients. A clue may lie in a group of commonly used medicines, called renin-angiotensin system (RAS) inhibitors, including ACE inhibitors and angiotensin receptor blocks or ARBs, usually extremely protective for our cardiovascular patients. But they have come under attack because they are suspected to increase the levels of ACE2 in the body, also part of RAS, which is the receptor for the virus, or the doorway for virus to enter our body. So are these agents safe or dangerous? This has become a major source of fear for both patients and physicians alike, and a raging controversy. To answer this question, we analyzed data from Wuhan, and found that these agents actually to be extremely protective. This finding was also replicated in another study examining patients in Europe and America. However, these data looked backwards at events past, which can be fraught with hidden biases. Therefore, the world desperately needs a proper forward-looking trial to evaluate these agents in COVID-19. Together with our Canadian and international partners experienced in COVID-19 research, we are starting this large trial to evaluate whether adding ACE inhibitors, or ARB's, compared to no added treatment in high risk COVID-19 patients, can decrease the chance of dying, requiring ventilators or ICU. A positive trial showing benefit will potentially save many lives in the world, using a very simple and cheap set of medications. Even if we found the medications to be safe, it will be very reassuring for millions of patients. We want to answer this question with urgency to benefit Canadians and cardiovascular patients worldwide in this COVID-19 era.",2021,2022,Ottawa Heart Institute Research Corporation (Ontario),39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trial (unspecified trial phase)",2021 +C19578,202102VS1,COVID-19 Variant Supplement - Inferring undiagnosed sources of COVID-19 infections using viral genomes,"The ongoing COVID-19 pandemic is believed to be significantly influenced by asymptomatic SARS-CoV-2 patients. Understanding the role that asymptomatic patients play in the spread of the disease is vital for informing testing procedures. This project aims to build a tool to identify asymptomatic or undiagnosed patients by examining infected people around them without the need to directly test them, allowing health authorities to make rapid and better informed decisions. Viral genomes accumulate small changes, mutations, which usually are neutral in terms of disease progression. These can be used to trace transmission networks - individuals within the network will have acquired the disease from a single source and so will share the same variants. Current approaches do not detect utilize all variants especially the low-frequency ones and so rate less robust in building accurate transmission networks, and inferring transmission by asymptomatic carriers. By utilizing our previously developed tools and expertise in inferring HIV transmission networks, we will develop new mathematical models that are able to infer SARS-CoV-2 transmission. The sequencing data needed to map viral transmission will be acquired through a project funded by the Alberta Children's Hospital Research Institute (ACHRI) and Genome Alberta, which aims to sequence 1,900 COVID-19 patients. In collaboration with our partner organization, Public Health Laboratory under Alberta Health Services (ProvLab) who performs COVID-19 diagnostics for the province of Alberta, we will obtain information on asymptomatic patients who have tested positive for the virus, remove them from our data, and then see if we can retrospectively identify them as likely contacts between the symptomatic individuals.. The resulting tools can be extended for use across Canada, and potentially even model future outbreaks of infections diseases in humans, livestock, and wildlife.",2021,2022,University of Calgary,39500,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics,2021 +C19579,202102VS1,COVID-19 Variant Supplement - Innovative therapeutic approaches for the 2019-novel coronavirus,"The 2019-novel coronavirus (SARS CoV-2) is a major sanitary and economical threat to all countries. Development of effective antivirals is a major global priority especially early in the epidemic when vaccines are unavailable. This proposal aims at discovering and evaluating active compounds by rational design through 3D modeling of key viral proteins and also by analyzing cellular gene signatures induced by the virus. In-depth evaluation of selected compounds will include in vitro, ex vivo (human bronchial epithelium tissues) and in vivo (animal models) studies. These approaches, mostly based on drug repurposing (new indication for an existing drug), will result in rapid identification of anti-SARS CoV-2 compounds with accelerated clinical development.",2021,2022,Université Laval,39500,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19580,202102VS1,COVID-19 Variant Supplement - Mitigation strategies against the public transmission of airborne COVID-19 in high occupancy structures: a program of research to develop optimized mechanical ventilation systems,"This research program brings together experts in Engineering and Medical Sciences to develop Non-Pharmaceutical Interventions (NPI) related to mechanical ventilation systems in buildings. These settings have high concentrations of humans in enclosed spaces where the spread of airborne infections can have rapid, extensive, and detrimental consequences in terms of morbidity, mortality, and ultimately productivity and costs. This research program targets a key mechanism of COVID-19 transmission, that is, transport of the virus through heating, ventilation, and air conditioning (HVAC) systems with subsequent inhalation by other people. Currently, it is not clear how human-generated bioaerosols affect airborne virus transmission and how HVAC systems should be optimally designed and operated to reduce the risk of transmission. This research program will include: 1) a thorough review of building science literature related to airborne virus transmission; 2) a policy directive for governing organizations who inform owners and operators of ventilation systems and building code bodies; 3) an inventory and assessment of over 100 buildings with diverse ventilation systems; and 4) an inventory and assessment procedure and protocol for other buildings. This research directly aligns with the objectives of the funding opportunity, in particular, to mitigate the rapid spread of COVID-19 and its potential negative consequences. Based on the research results, we will develop evidence-based guidance and policy recommendations to inform the design/re-design of buildings. This work has the potential for widespread impacts in terms of establishing policy and procedures that can be applied locally, nationally and internationally. Further, this research will inform the immediate response to the COVID-19 outbreak while having a broader impact in terms of the spread of other airborne illnesses/contagions and future outbreaks.",2021,2022,University of Alberta,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C19581,202102VS1,COVID-19 Variant Supplement - Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),"SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",2021,2022,Unity Health Toronto,39500,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies | Clinical trial (unspecified trial phase),2021 +C19582,202102VS1,COVID-19 Variant Supplement - Neutralizing Antibodies as SARS-CoV-2 Therapeutics,"Three highly virulent coronaviruses - SARS-CoV, MERS-CoV and SARS-CoV-2 - have crossed species barriers to infect humans since 2003. SARS-CoV-2 is responsible for COVID-19, a disease that arose in Wuhan China in December of 2019. The virus has infected over 64,000 people and caused 1380 deaths and the World Health Organization has declared it a public health emergency of international concern. Although drastic measures are being taken to contain SARS-CoV-2, there is an urgent need for new therapeutics to combat this virus and reduce its spread. In this work we will develop therapeutics based on human antibodies that can be used in the treatment of COVID-19.",2021,2022,University of Toronto,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19583,202102VS1,COVID-19 Variant Supplement - Neutralizing human-derived single-chain antibodies against SARS-CoV-2,"SARS-CoV-2 is a virus that has caused an epidemic of human respiratory disease (COVID-19). It first emerged from the city of Wuhan in Hubei in December 2019 and has since spread widely in China and to more than 24 counties globally. The virus has been declared as a deadly global threat, and accelerated international efforts have been engaged to control the virus. A total of 1,524 deaths been confirmed as of 15th February 2020 (WHO). As a result of the rapid transmission internationally, a global call to control the spread of the virus in affected and non-affected areas has been implemented. Currently, there is no effective treatment or vaccine to control the virus. Symptoms of the infection include respiratory symptoms, fever, cough, and shortness of breath. In more severe cases, the infection can cause respiratory failure, severe acute respiratory syndrome, kidney failure, and death. The objectives of this application are 1) to develop antibodies that will block the entrance of the virus into the cells, and to test the efficacy of these antibodies in mice.",2021,2022,University of British Columbia,39500,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19584,202102VS1,"COVID-19 Variant Supplement - Optimizing polar, small inhibitors of a viral cysteine protease to identify a lead for an oral COVID-19 treatment","The COVID-19 pandemic has caused incredible social, personal and economic upheaval and as of early May 2020 killed 275 000 people world-wide and, tragically, is projected to kill millions more. COVID-19 is caused by the SARS-CoV2 (SARS2) virus, which is a coronavirus closely related to SARS. These viruses infect cells and using the host's enzymes and virally encoded proteins create copies of themselves. These viral proteins are different than the host ones and are key targets to stop the viral replication. One such protein for SARS2, nicknamed 3CLP, is key to liberating the viral proteins in order to enable viral replication. Last month compounds we tested strongly inhibited the SARS2 3CLP and were able to inhibit SARS2 replication in a cell-based assay. This proposal is to design and make modifications of those compounds to better inhibit SARS2 and also optimize drug-like properties to discover a Lead compound for the ultimate development of an oral drug to treat COVID-19.",2021,2022,University of Alberta,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19585,202102VS1,COVID-19 Variant Supplement - Peptide macrocycle decoys against COVID-19 viral spike protein,"Peptides are potent, easy-to-synthesize, and synthetically accessible molecules that can specifically interact with pathogens. Peptides have been used to treat diabetes, neuropathic pain, cancer, and HIV. As chemists we have very recently invented news ways to make peptides both more potent as well as fluorescent in order to see where they go and how they act. We are poised to interface our technology with molecular modelling to synthesize peptides that will intercept the virus before it can enter a cell. These peptides can be injected or nasally delivered for therapy and can be used prior to vaccine development or in cases where certain patients cannot be vaccinated.",2021,2022,University of British Columbia,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19586,202102VS1,COVID-19 Variant Supplement - Point of Care Heart-Lung Imaging for Patients Presenting with COVID-19 Symptoms: Artificial Intelligence Precision Modeling for Prediction of Outcomes,"point of care ultrasound (POCUS)] when patients first enter the hospital, by any physician with remote support from POCUS experts. In this study, we will test if adding heart and lung ultrasound images to existing clinical and laboratory tests can improve the accuracy and speed of COVID-19 diagnosis. A total of 16 hospitals across British Columbia and Ontario will participate in this study, and we will analyze this large data set using artificial intelligence (AI). Our team has already developed a platform to share ultrasound data and applied AI to study other heart diseases, so we are ready to rapidly apply this approach to COVID-19. If POCUS is effective it would allow earlier treatment and isolation of positive cases, reducing exposure of frontline health care workers and the public to the virus, improving both patient care and the distribution of health resources like personal protective equipment, intensive care beds and ventilators. Because POCUS-based COVID-19 diagnosis can be performed remotely it could also be applied in long term care facilities and in rural areas.",2021,2022,University of British Columbia,39500,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19587,202102VS1,COVID-19 Variant Supplement - Predicting the risk of developing mental and substance use disorders due to COVID-19: machine learning applied to health service utilization data to facilitate access to effective treatments.,"COVID-19 has caused unprecedented demand on health care systems worldwide. Early indications suggest that the pandemic will lead to a surge in mental health and substance use disorders. This study aims to examine these mental and substance use implications through comparison of patient cohorts in BC, Canada based on their ""illness dose"" of COVID-19. In partnership with the Health Authorities and the BC Ministry of Health, we will deploy an online survey to assess these patient groups to detect the new onset or worsening of mental and substance use disorders that may be attributed to COVID-19. We will leverage Population Data BC, one of the world's largest collections of health services data containing individual-level, de-identified longitudinal data on BC's 4.7 million residents. We will link our survey results with data available at Population BC data, in order to retrospectively study the sociodemographic, service utilization, prescription drug use, employment, and environmental exposures of patients over the past 10 years. Using machine learning methods (Artificial Intelligence) to compare these different cohorts, each of which represents different ""doses"" of exposure to COVID-19, we will identify patients that are at increased risk of developing COVID-19-related adverse mental health outcomes. We will follow up with COVID-19 positive patients through a virtual clinic and assess existing treatment options for mental and substance use problems. Ultimately, we will have a system to predict increased risk of neuropsychiatric impact of COVID-19 on patients in BC, and to facilitate access of these patients early on to existing mental health services. This important data will allow Health Authorities to prepare for subsequent waves of COVID-19 with the tools required to rapidly mitigate its adverse effects on mental health and substance use.",2021,2022,University of British Columbia,39500,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2021 +C19588,202102VS1,COVID-19 Variant Supplement - Preventing SARS-CoV-2 infection by targeting human type II transmembrane serine protease activity,"The SARS-CoV-2 coronavirus causing COVID-19 has been declared a global emergency by the World Health Organization which has mobilized international scientists to collaborate in order to find therapies to counteract the virus's effects which can be devastating. The strategies need to be as vast as possible since we do not yet know if vaccines or other antiviral drugs will be efficacious. Our group had previously shown in the context of influenza infection that the human host has cell-surface proteases (called type II transmembrane serine proteases or TTSPs) that the virus requires in order to cleave a viral surface protein called hemagglutinin, itself essential for the virus to gain entry into the cell and further replicate using the host cell machinery. We had shown that small molecules inhibiting the activity of lung epithelial cell proteases were efficacious at significantly reducing influenza virulence demonstrating novel anti-viral properties of the compounds. The situation is similar with the SARS-CoV-2 virus but the protein found on the surface of the virus is different. This protein is called the spike glycoprotein (or S protein) and it requires cleavage by human host cell proteases of the TTSP family for its virulence. Our proposal will test protease inhibitors in models where cells are expressing the S protein and the most potent molecules will then be validated in lung organoids to verify their efficacy at reducing viral propagation. We have put together a team of molecular pharmacologists, chemists and virologist with access to containment level 3 facilities to rapidly assess the potential anti-viral properties of the compounds that we already have on hand. In addition, our team will be supported by Dr. Gary Whittaker, Cornell University, one of the world's expert in coronavirus biology. We believe that these conditions are very favorable for us to have a quick impact in the field and to deliver novel antiviral compounds for patients with COVID-19.",2021,2022,Université de Sherbrooke,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19589,202102VS1,COVID-19 Variant Supplement - Production of a recombinant S ( spike ) protein vaccine against SARS-CoV-2 and emerging coronaviruses,"In December 2019 a human coronavirus (CoV) outbreak causing pneumonia-like symptoms began, centered around a fish market in the Wuhan district of China. After the genomic sequence was determined the causative pathogen, SARS-CoV-2, showed 99.98% identity among 9 patients, was 88% identical to two bat SARS-like CoV, ~79% identical to SARS-CoV, and ~50% identical to MERS-CoV (Tan 2020 Lancet). SARS-CoV and MERS-CoV were responsible for severe human illness and mortality (~10% in 2002 and ~35% in 2013, respectively). Although understanding of SARS-CoV-2 and the COVID-19 disease is ongoing, it is believed human-to-human transmission is possible and the disease fatality rate is ~2-3%. In early February 2020, WHO reported >31,000 confirmed human infections, >640 deaths, and declared a Public Health Emergency of International Concern, presumably due to the possibility of a pandemic. The coronavirus 2019 outbreak is the third coronavirus outbreak causing a severe human disease in the past ~20 years. Currently a coronavirus prophylaxis vaccine and therapeutic drugs are not available. In this application we describe the investigation of vaccine candidates. Our team has manufacturing experience expressing a subunit Hepatitis-C virus vaccine candidate and has developed methods for industry-scale vaccine purification using removable purification tags (Logan 2017 Journal of Virology). This work will identify a CoV vaccine candidate that can proceed to the creation of a manufacturing grade mammalian cell line.",2021,2022,University of Alberta,39500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2021 +C19590,202102VS1,COVID-19 Variant Supplement - Protecting healthcare workers from COVID-19: A comparative contextualized analysis,"This research focuses on measures to protect healthcare workers (HCWs) who are at substantially increased risk because of their direct contact with COVID-19 infected patients - and with considerable variation being experienced internationally in different settings. Although there is general agreement on many aspects of policy to protect HCWs, approaches have varied widely with very limited availability of contextualized evidence to guide local decisions. Often differences have been due to availability of specific personal protective equipment (PPE-e.g. N95 respirators, masks, gloves, gowns); sometimes differences have been due to operational necessities (e.g. whether exposed HCWs can continue to work while wearing PPE); sometimes variations in policies relate to availability of COVID-19 test kits or related reagents (e.g. criteria for testing or whether pre-return-to-work testing is implemented); approaches to exposure monitoring and contact tracing for HCWs also vary widely. It is critically important for policymakers to understand consequences of these variations, as well as scrutinize their scientific and contextual rationales. This proposal asks ""What works to protect HCWs, in what contexts, using what mechanism, to achieve what outcome?"" By building on a strong track record of interdisciplinary research in exactly this field, with well-established international networks with expertise in infection control and occupational health, and a long-history of relationship-building to facilitate this research, this team is extremely well-positioned to conduct this highly relevant research and provide world leadership in this area. It will be conducted through in-depth case studies conducted in Vancouver, Canada and Gauteng, South Africa as well an international cross-country comparative analysis based on surveys and experiences in protecting healthcare workers and a case-control study of workers with COVID-19 infection versus other workers in their same facilities.",2021,2022,University of British Columbia,39204.54,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C19591,202102VS1,COVID-19 Variant Supplement - Rapid bench-to-human development of safe and effective aerosol vaccine strategies against Covid-19,"The pandemic of Covid-19 caused by respiratory SARS-CoV-2 infection has brought the world to a standstill. The physical-distancing strategy currently implemented in the pandemic aims to prevent the majority of Canadians from being infected by SARS-CoV-2. While this is an essential short-term strategy to save lives, it will paradoxically leave the majority of our citizens without protective immunity against Covid-19. Thus, the majority of Canadians will be susceptible to the next waves of Covid-19. The only effective way to prevent new outbreaks from getting out of control is to establish herd immunity via implementing a safe and effective vaccination program prior to the next waves of Covid-19. High-risk Canadians including healthcare workers, seniors and indigenous people are especially in need of such vaccine-induced protective immunity. A global effort has been initiated to identify effective Covid-19 vaccines, testing a variety of vaccine platforms and strategies. Unfortunately, only a few of them are being developed and tested in Canada and almost none of them are designed to target respiratory mucosal immunity. To fill the gap, via the effort from a multi-disciplinary McMaster Team we have been rapidly developing innovative recombinant viral-vectored Covid-19 vaccine strategies to target the desired respiratory mucosal immunity. Our Team has internationally recognized reputation in bench-to-human translational vaccine research. Particularly relevant to the proposal is our strong expertise in advanced viral vector bioengineering, vaccine efficacy testing in small animal models at CL3 facility, clinical-grade vaccine production at GMP manufacturing facility, optimized inhaled aerosol vaccine delivery method, and clinical vaccine trials. We are confident that our project will make available to Canadians a superb, needle/pain-free vaccine strategy capable of potent respiratory mucosal protection against Covid-19.",2021,2022,McMaster University,39500,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies | Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2021 +C19592,202102VS1,COVID-19 Variant Supplement - Rapid development of antiviral compounds to fight the COVID-19 outbreak,"The outbreak of a respiratory illness (COVID-19) in China at the end of December 2019 has been demonstrated to be caused by a new coronavirus. While health officials are using quarantine methods to try and prevent the spread of the infection, there are currently no treatments for the illness, which can be severe and even lead to death in 2% of cases. Here, we propose to build on our previous research with viruses of the same family, which include those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We have previously successfully engineered small proteins capable of blocking the activity of an enzyme of the virus that is crucial for its replication and for shutting down the human immune response. We plan on using a similar strategy to build blockers of the new virus. These will be extremely useful in better understanding the biology of the virus. Most importantly, we will use these blocking proteins to find chemical drug candidates that block the activity of the viral enzyme in infected cells, which can then be developed as therapeutics. Our method is rapid and cost efficient, and within the two years of this grant, we expect to have a number of lead candidate drugs. In order to achieve these goals, we have assembled a team of leading scientists with expertise in protein engineering of viral inhibitors (Sachdev Sidhu, University of Toronto), structural biology of viruses (Brian Mark, University of Manitoba), and development of chemical drugs (Roman Melnyk, SickKids Research Institute, Toronto). Our project also has the support of an internationally recognized leader in viral biology (Marjolein Kikkert, Leiden University, Netherlands) and a frontline clinician-scientist in infectious diseases (Samira Mubareka, Sunnybrook Health Centre, Toronto). Ultimately, this work will generate critical tools to better understand this new virus, and most importantly, will provide novel candidate drugs for direly needed therapies.",2021,2022,University of Toronto,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19593,202102VS1,"COVID-19 Variant Supplement - Rapid, Ultrasensitive Clinical Detection of 2019 Novel Coronavirus (nCOVID-19) by Novel Microfluidic Electrochemical Nano-Biosensors","In December 2019, a novel coronavirus (2019-nCoV) emerged in the city of Wuhan, in China and has spread widely, including Canada. In a few weeks, the number of confirmed cases of COVID-19 infection has dramatically increased. Currently, 20-25% of confirmed cases have severe clinical presentations. With no vaccines nor specific treatments, early confirmation before progression to late stages would provide more time for effective supportive treatment. The traditional detection process requires that samples from sick individuals be transported to laboratories for manual processing. This is extremely inefficient and introduces a significant time-delay that has severe consequences for disease spread. Since January 2020, tests have become increasingly available for clinically suspected patients. However, despite the high sensitivity of these methods, they are not suitable for rapid and large-scale screening for multiple samples because of their long analysis time. Moreover, these methods need skilled personal to perform and not suitable for point-of-care testing. Most of these assays have not been yet adopted for COVID-19. The objective of this project is to develop a novel diagnostic tool for rapid detection of early-stage COVID-19. The device will have an impact to timely inform and refine strategies that stop the spread of the disease.",2021,2022,University of Calgary,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C19594,202102VS1,COVID-19 Variant Supplement - RIsk of environmental Surface and air Contamination in COVID19 (RISC-COV),"This study has three goals. First, we will collect clinical and epidemiologic information about COVID-19 in Toronto and Peel region to share with ISARIC studies of the risk factors for, clinical features and outcomes of this infection in Canada and around the world. Second, we will collect data about how long patients with this infection shed virus, and whether this virus can be found on surfaces and in the air around patients with this infection, in order to help guide infection prevention practice. Third, we will systematically collect samples containing the virus, serum and cells of the immune system, in order to create a biobank that can be shared with investigators developing vaccines and treatment for this disease.",2021,2022,Sinai Health System (Toronto),39443.12,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Environmental stability of pathogen | Disease transmission dynamics | Disease pathogenesis",2021 +C19595,202102VS1,COVID-19 Variant Supplement - SARS-CoV-2 immunization strategies to enhance protective immunity with reduced risk of antibody-dependent enhancement (ADE),"A pandemic of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) that emerged from China late in 2019 is currently underway resulting in worldwide severe morbidity and mortality. Thus, a safe and effective vaccine is urgently needed to fight virus propagation. In this project, after identifying and engineering the immunogens, we will translate towards SARS-CoV-2 a versatile, potent and immunostimulating nanotechnology platform recently developed in our laboratory, which not only will adequately present the vaccine materiel to the host immune system but also enhance its immunogenicity, while eliminating the risk associated with the so-called antibody-dependent enhancement (ADE). The gathered investigative team integrates a unique set of complementary knowledge including biophysics, protein engineering, virology and immunology, which is perfectly suited to rapidly address the health challenges of the COVID-19 pandemic, and has the necessary expertise and state-of-the-art infrastructure to conduct the proposed research.",2021,2022,Université du Québec à Montréal,39500,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2021 +C19596,202102VS1,COVID-19 Variant Supplement - SARS-CoV2 therapeutic discovery through genetic screens and repurposing drugs that target essential virus-host interactions.,"The worldwide pandemic of COVID19 caused by the virus SARS-CoV2 has caused over 270,000 human lives and worldwide economic collapse. While public health measures such as social distancing and shutdown of non-essential businesses have been effective at slowing virus spread, restarting society and economies in Canada and around the world will require intensive testing and contract tracing, and ultimately effective treatments and vaccines. In this proposal our goal is identify existing therapeutics that can be re-purposed to treat SARS-CoV2 infections. During an infection viruses must hijack host machinery and regulatory pathways in order to reproduce, and some of the pathways used by viruses are the same ones that are dysregulated during human diseases such as metabolic diseases and cancer. Thus, it is likely that therapeutics designed to treat metabolic diseases and cancer also inhibit SARS-CoV2 infections. However, the specific machinery and regulatory pathways used by SARS-CoV2 remain unknown and the potential inhibitors undiscovered. Our strategy is to identify the host machinery and regulatory pathways the virus needs to grow, and then test drugs that target these proteins to see if they inhibit SARS-CoV. Finally, many different types of coronaviruses likely also use the same host machinery and regulatory pathways so the inhibitors we discover might also be effective against other coronaviruses so could help society prepare for future coronavirus outbreaks and avoid future pandemics.",2021,2022,University of Saskatchewan,39500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Prophylactic use of treatments",2021 +C19597,202102VS1,COVID-19 Variant Supplement - Screening Student Resiliency and Mental Health Indicators During School Re-Entry,"COVID-19 displaced millions of students from their schools, teachers, and peer groups. Early data proclaimed everything from a second ""mental health pandemic"" wave to significant expressions of strength and resilience. The primary research question is: What are the self-reported mental health needs and resiliency indicators of students returning to school amidst COVID-19? This information is urgently needed by schools to ensure effective, appropriate, and time sensitive mental health supports are available to returning learners in their metropolitan schools (Catholic and public) in two major Canadian cities. This study will measure behavioural and mental health functioning and resilience in a large sample (N approx. 3000) of metropolitan school district students at the time of school re-entry and again at 3, 6, and 9 months post school re-entry. Students will complete measures of COVID-19 health behaviours, mental health symptoms and adaptive behaviours, and resiliency. Results will inform strategic planning related to student services for these school districts and assist in the development of system-wide intervention and resource allocation for students returning to school in Fall, 2020. Knowledge translation activities will include dissemination of results to the metro school districts via reports, data webinars, infographics, social media platforms, and peer-reviewed publications. In summary, the present study will assist four major metro school districts to gather screening data useful for prioritizing district-wide initiatives that can inform strategies to build on identified strengths and remediate self-reported learning, behavioural, and social-emotional needs of students upon school re-entry.",2021,2022,University of Calgary,38759.77,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19598,202102VS1,COVID-19 Variant Supplement - Shutting down emerging Coronaviruses in humans now and in the future,"In December 2019, a pneumonia associated with the 2019 novel coronavirus SARS-CoV-2 emerged in Wuhan, China. This disease is now named COVID-19. Over 73,000 people have been infected worldwide and over 1,700 people have died from the disease. There is no sign that the rate of new infections and deaths are levelling off or showing signs of declining. Similar coronavirus outbreaks in the future are always a risk and must be addressed now. The goal of this proposal is to establish and test an effective vaccine for SARS-CoV-2. In addition, we will develop a coronavirus vaccine bank containing hundreds to thousands of potential vaccines that can be used at the start of the next coronavirus outbreak. This will give us a head start in trying to treat patients early with the goal of reducing the spread of the disease and subsequent fatalities.",2021,2022,Western University,39500,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine logistics and supply chains and distribution strategies,2021 +C19599,202102VS1,COVID-19 Variant Supplement - Targeting genetic and chemical vulnerabilities of novel coronavirus SARS-CoV-2,"The recent outbreak of the SARS-CoV-2 coronavirus in China and its continued international spread threatens to become a global pandemic. Although coronaviruses generally cause mild respiratory infections in humans, over the past 18 years, three animal-derived coronaviruses have emerged that cause much more severe disease: SARS-CoV, MERS-CoV, and the current SARS-CoV-2. Each of these emergent viruses cause substantially higher death rates than common coronavirus infections; the current estimate of the death rate due to COVID-19 syndrome caused by SARS-CoV-2 infection is ~2.5%. The main challenge in addressing these new coronavirus-associated outbreaks is a lack of suitable therapeutics to treat active disease (i.e., anti-viral drugs) or to prevent disease (i.e., appropriate vaccines). We propose to apply genomics-based tools and drug-screening platforms to rapidly pinpoint new targets for SARS-CoV-2 anti-viral agents and to identify candidate therapeutic compounds. Our team has deep expertise in anti-infective drug discovery, the application of genomics in identifying drug targets, and in the biology and biochemistry of RNA viruses such as SARS-CoV-2. Our project will identify new therapeutic strategies that may help to treat COVID-19 patients. These strategies will also help mitigate newly emergent coronavirus-associated diseases that will undoubtedly continue to cause outbreaks in the future.",2021,2022,McMaster University,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19600,202102VS1,COVID-19 Variant Supplement - Targeting programmed ribosomal frameshifting as a therapeutic strategy against 2019-nCoV,"The new coronavirus 2019-nCoV has spread rapidly in the last 3 months, infecting tens of thousands of people in dozens of countries and killing over 1,000, with no preventive vaccines or medications that can treat it. We propose to search for possible drugs to treat 2019-nCoV by targeting the ability of the virus to hijack the cell's machinery and recode how the genome is read via programmed ribosomal frameshifting (PRF). Coronaviruses use PRF, which is triggered by a specific structure (a 'pseudoknot') in the viral genome, to produce essential enzymes in specific ratios. Suppressing PRF in SARS coronavirus-which is very closely related to 2019-nCoV-disrupts viral propagation and significantly reduces infectivity, suggesting that PRF inhibitors could be used to combat 2019-nCoV. We will search for potential drugs that bind to the 2019-nCoV pseudoknot and disrupt PRF. We will first build a structural model of the pseudoknot by combining computational simulations with measurements revealing the base-pairing patterns and higher-order structures in the RNA. We will then use high-throughput computational tools to screen large libraries of existing approved drugs (which could be deployed rapidly), as well as publicly-available chemical compounds, for binding to the pseudoknot. Compounds predicted to have high binding affinity will be tested experimentally to confirm their binding-quantifying the binding affinity, identifying the binding site, and showing that binding alters the pseudoknot structural dynamics (thought to be important for triggering PRF)-and to measure their effectiveness at inhibiting PRF in cell extracts. We will examine if the effects of the compounds are specific to 2019-nCoV by repeating all measurements using other RNA structures as controls. Lead compounds will be passed on to collaborators for future studies assessing their effectiveness against live virus and suitability for deployment as therapeutics.",2021,2022,University of Alberta,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C19601,202102VS1,"COVID-19 Variant Supplement - The COVID-19 Hospital Analytics Laboratory: Improving the Clinical, Organizational, and System Response to COVID-19","Hospital care has been dramatically reorganized to respond to the COVID-19 pandemic, with an urgent need to preserve scarce resources like ventilators and personal protective equipment. Yet, there is minimal evidence about how to care for patients with COVID-19 in hospital and how to maintain high quality non-COVID care during the pandemic. Detailed clinical data, such as patient vital signs or medications, are needed to study COVID-19 and its individual- and system-wide effects. These data are available in hospital computer systems but have not been widely collected and shared for research. The General Medicine Inpatient Initiative (GEMINI) has collected detailed clinical data from >340,000 admissions at 7 hospitals in Ontario, making it the largest inpatient repository about adult medicine in Canada and a valuable data source to study COVID-19. We propose to create the COVID-19 Hospital Analytics Laboratory by extending GEMINI to the 30 largest hospitals in Ontario, representing 70% of acute medical/ICU beds in the province. We will collect detailed clinical data from all medical and ICU admissions, including COVID-19 and other medical illnesses. Data will be linked to ICES longitudinal population datasets and updated every 1-3 months to create a globally unique platform that enables advanced analytics and machine learning and includes a diverse sample of patients, meaning research insights will be widely applicable. This platform will address all 5 CIHR objectives by supporting a breadth of research focused on improving hospital care in the setting of COVID-19. Data will be accessible to global experts in artificial intelligence, operations engineering, population modeling, public health and clinical epidemiology. Our first two research priorities will be to improve understanding and prediction of clinical outcomes in patients hospitalized with COVID-19 and to study how the organization of hospital care in the setting of COVID-19 affects patient outcomes.",2021,2022,Unity Health Toronto,39500,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Disease pathogenesis | Supportive care, processes of care and management | Health service delivery",2021 +C19602,202102VS1,"COVID-19 Variant Supplement - The COVID-19 Ontario Pregnancy Event (COPE) Network: Assessing the impact of COVID-19 in pregnancy on maternal, fetal and newborn health","Data collection and research on COVID-19 in pregnancy are urgently needed to fill the many knowledge gaps about the impact of COVID-19 on maternal, fetal and newborn health. We propose to leverage Ontario's birth registry, and the COVID-19 Ontario Pregnancy Event (COPE) Network - a collaboration of 12 obstetrical hospitals in 5 of Ontario's largest cities - to launch a series of seroprevalence, vertical transmission and surveillance investigations that will generate rapid, rigourous evidence on the impacts of COVID-19 in pregnancy. We will achieve this by (1) implementing universal screening of all pregnant women to assess the prevalence of symptomatic and asymptomatic SARS-CoV-2 infection; (2) generating complete infection and antibody profiles of maternal and newborn tissues to assess the mother-to-infant transmission potential of SARS-CoV-2 among mothers affected by COVID-19; and (3) generating in-depth obstetrical profiles of pregnancies affected by COVID-19 to assess clinical characteristics, case management and maternal and neonatal outcomes associated with infection during pregnancy. Our multi-disciplinary, high-qualified team has an established track-record in pregnancy and birth cohorts, molecular virology and infectious diseases, and are well-positioned to fulfill these objectives. Our findings will inform strategies to optimize processes in care, patient counselling and health systems management specific to the obstetrical and neonatal population, and will lay the foundation for follow-up studies to assess the longer-term health implications of COVID-19 on infant health. The relevance of our findings will not be limited to Ontario but will be of value to clinicians and families across Canada and globally.",2021,2022,Ottawa Hospital Research Institute,39500,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Immunity | Disease transmission dynamics | Disease pathogenesis | Supportive care, processes of care and management",2021 +C19603,202102VS1,"COVID-19 Variant Supplement - The COVID-19 Pandemic Among Sexual and Gender Marginalized Populations in Canada: Physical Distancing Impacts, SARS-CoV-2 Seroprevalence, and Health and Wellness Needs","Physical distancing may have especially negative effects on marginalized communities such as lesbian, gay, bisexual, trans, queer, Two-Spirit, and other sexual and gender marginalized people (LGBTQ2+). LGBTQ2+ people are more networked socially and sexually compared with other groups. LGBTQ2+ also experience other health inequities such as cardiovascular disease, poorer mental health, and more substance use that may result in greater COVID-19 impacts. This study will determine how COVID-19 impacts LGBTQ2+ people across Canada. We will conduct an online survey of LGBTQ2+ people. Our findings will inform future public health action for LGBTQ2+ people to avoid unintended consequences such as intimate partner and family/domestic violence, anxiety, and depression. Participants will also be mailed a kit to collect a few blood drops to test for COVID-19. This approach may be an important tool for future COVID-19 testing, especially among rural, remote, and Indigenous communities.",2021,2022,University of Victoria (British Columbia),39500,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Indigenous People | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Research to inform ethical issues related to Public Health Measures | Approaches to public health interventions | Indirect health impacts,2021 +C19604,202102VS1,COVID-19 Variant Supplement - The role of interleukin-10 responsiveness in lung inflammation in SARS CoV2 infection,"A subset of patients infected by SARS CoV2 respond with overproduction of inflammatory cytokines which contribute to their acute respiratory distress and morbidity. This ""cytokine storm"" results from the imbalance between inflammatory and anti-inflammatory mechanisms. One of these mechanisms involve inflammatory macrophages which produce cytokines such as interleukin-6 and interleukin-1, and anti-inflammatory, regulatory macrophages which predominantly produce the anti-inflammatory cytokine interleukin-10 (IL10). IL10 acts on the inflammatory macrophages to temper their response. We propose to examine whether the regulatory, IL10-producing macrophages in the lung are producing appropriate levels of IL10, or whether the inflammatory macrophages are impaired in their ability to respond to IL10. We will also assess whether a small molecule SHIP1 agonist which activates the intracellular protein SHIP1 like IL10 does, can mimic the action of IL10 and reduce inflammation in SARS CoV2 infection.",2021,2022,University of British Columbia,39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C19605,202102VS1,COVID-19 Variant Supplement - Therapeutic approaches to SARS-CoV-2 and other pathogenic coronaviruses,"Coronaviruses can cause serious diseases in humans and animals. Over that last two decades, we have seen the emergence of three deadly coronaviruses, the most recent of which SARS-CoV-2 is still spreading rapidly. Antivirals developed for other viruses are presently being tested in clinical trials in China, but there is no indication that these drugs will work against SARS-CoV-2. Currently, public health measures and quarantine are the only means to limit spread of SARS-CoV-2. As such, antiviral therapeutics and vaccines are both desperately needed to mitigate the effects of SARS-CoV-2 and future coronavirus outbreaks. Here, we present a strategy for testing novel antiviral drug candidates and vaccines as well as molecular tools to understand SARS-CoV-2 biology. By focusing initially on drugs already approved for use in humans for other indications, our goal is to identify compounds with activity against SARS-CoV-2 that can be rapidly approved for use in the clinic. In addition, our expertise in immunology and vaccinology against coronaviruses positions us very well for developing novel vaccine candidates. Finally, we will create molecular tools including modified SARS-CoV-2 viruses. Some of these tools which will not require high level containment, will be made available to a wide group of researchers so that they can also screen for antiviral compounds and study virus biology without the need for specialized containment facilities.",2021,2022,University of Alberta,39131.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2021 +C19606,202102VS1,COVID-19 Variant Supplement - Towards a comprehensive understanding of adaptive immunity to SARS-CoV-2,"The vast majority of people who get COVID19 fully recover from infection. This means that their immune system has successfully eliminated the virus. After we recover from a virus infection, the immune system leaves behind white blood cells, called memory cells, that can remember the previous infection and prevent that infection from recurring upon re-exposure. This is the basis of how vaccines work. After we recover from infection, two kinds of white blood cells persist, T cells and B cells. T cells and B cells have molecules on their surface that allow them to recognize the specific virus they were first exposed to. B cells give rise to antibody producing cells, while T cells can eliminate infected cells. Some antibodies can bind the virus in such a way that they fully block the virus from entering the cell. These are called neutralizing antibodies and these are ideal to fully protect us from being infected again. However, in some infections, weak antibodies, instead of neutralizing the virus, can actually make things worse by promoting uptake of the virus into cells or by overstimulating certain cells of the immune system. Therefore, there is a pressing need to understand the details of the immune response in COVID19 patients. We need to understand what parts of the virus are recognized when we have an immune response associated with a good outcome and what if any aspects of T and B cell responses are associated with a bad outcome. By studying the immune response in asymptomatic, mild and severe cases in depth, we hope to determine the correlates of a good immune response and use this information to design vaccines and to monitor people for the correct immune responses. For some infections T cell and B cell responses last a lifetime, whereas for other infections they do not last as long. Our study will develop the tools we need to follow how long the immune response to COVID19 infection lasts and to help with evaluating the level of protection in the population.",2021,2022,University of Toronto,39500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C19607,202102VS1,COVID-19 Variant Supplement - Towards anti-COVID-19 therapeutic development by targeting the viral papain-like proteinase,"When positive-stranded RNA viruses such as the causative agent for the 2019-2020 novel coronavirus (SARS-CoV-2) outbreak enter an infectious cycle in the cell, their RNA genomes hijack the host cell's protein production machinery to mass produce large continuous viral polyproteins in a process called translation. In order to make progeny viruses, these viral polypeptides need to be processed into smaller, individually functional protein programmed to perform specific tasks, e.g., replicating the RNA genome, assembling the protein coat for progeny viruses, packing the newly synthesized RNA genome into the assembled viral capsid, and subverting or disabling the host cell's antiviral defense mechanisms. Two virally encoded proteinases, the papain-like (PL) and the 3C-like (3CL) proteinases, carry out the job of ""clipping"" the viral polypeptides into individual viral proteins. The PL is translated before the 3CL hence it likely takes precedence in performing ""cuts"" in the polyprotein, releasing an initial batch of viral proteins to mount the first wave of suppressive attack on antiviral host defense. In addition, coronavirus PL directly participates in preventing type I interferon activation, an important step leading to antiviral defense. Last but not the least, PL1 is part of non-structural protein 3 (NSP3), which is an indispensable component of the membranous complex where viral RNA genome is replicated. Taken together, PL of the novel coronavirus makes a good antiviral target for the development of therapeutics. Inhibiting PL would not only halt viral protein and RNA production at an early stage but would also help restore host antiviral defense. In this proposal, we seek to solve the 3-dimensional structure of SARS-CoV-2 PL and then use the structural knowledge to aid our search of small molecules that can inhibit the functions of PL. We will work with our collaborators to optimize the top inhibitors and test these inhibitors in cell and animal infection models.",2021,2022,University of Alberta,39500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +C19608,202102VS1,COVID-19 Variant Supplement - Understand the high pathogenicity and zoonotic transmission of the COVID-19 virus: evasion of host innate immune responses,"Coronaviruses are not new to humans. The human coronaviruses OC43 and 229E were discovered as early as in the 1960s. Both viruses cause common cold, a mild infection of our upper respiratory tract. However, the story started to change in 2002 when SARS broke out in China and other countries. This outbreak was caused by a new coronavirus which originally came from bats. Most importantly, this SARS coronavirus is highly pathogenic, with a fatality as high as 10%. Ten years later, a more deadly coronavirus caused the MERS outbreak. Now, a new coronavirus came back, is raging in China, may cause a global pandemic if not controlled. This new virus, COVID-19 (or SARS-CoV-2), has infected more and killed more than the total number by both SARS and MERS. Two urgent questions need to be addressed. How did these coronaviruses transmit from animals into humans? What have made them so pathogenic and lethal? Humans are protected from viral diseases by the immune system. These pathogenic coronaviruses must have found ways to evade the immune responses so that they can spread in humans and cause fatal illness. We thus propose this research to elucidate how this COVID-19 virus does this. The findings will identify the key viral genes that suppress immune responses by blocking essential signaling pathways. Our results will open new avenues for the development of effective interventions to halt the COVID-19 break.",2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,39500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C19609,202102VS1,COVID-19 Variant Supplement - Understanding the pathogenesis of COVID-19,"Pulmonary infections by viruses such virulent Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) and Middle East Respiratory Syndrome (MeRS) CoV associated with significant morbidity and mortality. Clinically, infections by these viruses are associated with a pronounced lung inflammation, causing respiratory problems that often develop in secondary pneumonia. Inflammation is the result of immune activation in response to infection. When activation is too pronounced or sustained for extended periods of time, complications occur. Two main mediators of inflammation are known: Cytokines and lipid mediators of inflammation (LMI). In the current proposal we will study the inflammatory response during infection/exposure of lung and blood cells to the newly described COVID-19 and compare this response to that of SARS-CoV-2 and MeRS-CoV to obtain correlates of pathogenicity between these viruses. We will use primary lung cells and white blood cells from donors to conduct our studies. The mediators of inflammation will be identified and quantitated using state of the art methodology available in our laboratories. More than 200 LMI and 150 cytokine/cytokine receptors will be examined. Upon completion of this proposal, a detailed analysis of the response of primary epithelial cells and leukocytes to COVID-19 will be obtained, enabling the rational design of therapeutic strategies to help combat COVID-19.",2021,2022,Université Laval,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +C19610,202102VS1,"COVID-19 Variant Supplement - Vaccine efficacy in nonhuman primates against SARS-CoV-2: protection, cross-protection and immune enhancement","In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. Since then (in only the last 5 months) this virus, has caused a global pandemic resulting in 4.2 million cases and over 288,000 deaths. Quarantine measures have not been sufficient to interrupt transmission despite near world-wide unprecedented disruptions of normal activities. Since its identification we have been working on making a vaccine to prevent infection with SARS-CoV-2. This vaccine contains a portion of the spike protein (the protein that is present on the surface of the virus) and when delivered to animals, induces an immune response. So far, we have shown that this vaccine can cause an immune response in ferrets, and early data suggests that to is also protective. To ensure that this vaccine is safe, immunogenic and effective we propose to test it in a nonhuman primate model of SARS-CoV-2. Typically nonhuman primates are the animal model that most closely resembles what happens in humans. To do this rapidly, we will vaccinated animals at the National Microbiology Laboratory with our vaccine to determine whether it induces the kind of immune response we want to see. Namely, whether it induces antibodies that are capable of blocking infection - called neutralizing antibodies. Finally, we want to demonstrate that this vaccine actually protects the animals from infection and does not cause any deleterious events, so animals will be infected and monitored to determine whether the vaccine stops infection. Subsequent experiments to support this data will be performed at VIDO-InterVac. Together this work will increase the capacity to assess other vaccine concepts that are being worked on across Canada to identify the best approach to stop transmission of SARS-CoV-2.",2021,2022,University of Saskatchewan,39500,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Disease models | Pre-clinical studies,2021 +C19611,202102VS1,COVID-19 Variant Supplement - Wastewater surveillance of SARS-COV2 to enable real-time clinical case-finding in Calgary,"We propose to track SARS-COV2 in the wastewater (WW; i.e., sewage) in Calgary, Alberta. The SARS-COV2 virus is excreted in the poop of infected individuals - often before symptoms start. These viruses are no longer infectious, but their genetic material (RNA genomes) can be detected in wastewater samples using molecular biology techniques for RNA quantification. This project will create a pathway enabling mobilized testing of the WW network throughout Calgary. Our project will achieve 3 objectives: 1 develop procedures to collect and analyse SARS-COV2 genetic material in WW samples from regionally diverse parts of Calgary, 2 develop different molecular assays that complement each other and are resilient to the WW chemical matrix, 3 develop genomics and bioinformatics methods for identifying genetic variants of SARS-COV2 in Calgary WW thereby enhancing epidemiological tracking. In Stage 1 we will develop and validate assays with samples from Calgary's three WW treatment plants, accounting for variability in WW chemistry and its effect on molecular biology methods. In Stage 2 we will work closely with Alberta Health Services and City engineers to apply the assays on WW from areas with known active COVID-19 cases to demonstrate proof of principle. In stage 3 we will deploy in real-time sampling teams through the city to collect samples for monitoring new areas where infections are not known to exist, allowing AHS to proactively find and respond to infected people without symptoms. Our team involves AHS, the City of Calgary, engineers, microbiologists, clinicians/public health experts, and University deans from Science, Engineering and Medicine. We will provide real-time, actionable information on SARS-COV2 in Calgary enabling public health officials to perform regionalized case-finding and develop strategies that focus containment efforts in the areas most affected, while minimizing the collateral social and economic consequences of needed public health interventions.",2021,2022,University of Calgary,39500,Viruses | Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen | Disease transmission dynamics",2021 +C19612,202002OV2,COVID-19: Improving the Evidence to Treat an Emerging Infection Through Observational Studies and a Randomized Trial,"The clinical management of COVID-19 remains unclear. First, we do not know what the disease is yet; we are still learning a great deal about what it causes in humans. We do not know what treatments to give, what risk factors are present for severe disease, and how long people are sick. We are proposing a national observational study of hospitalized patients with confirmed COVID-19, with an embedded randomized clinical trial of an antiviral agent. The observational study will build on work that we have been doing for the past four years, with pre-established protocols and data collection infrastructure just for this purpose. The randomized clinical trial will be with global collaborators to make sure that Canadian patients inform the world, and vice versa, about how to best treat this new disease. Alongside this, we will conduct surveys of clinicians, researchers, and the public about how they understand this new outbreak, how they feel about participating in research during a major outbreak, and what should be done differently; all of which will inform our clinical studies. Finally, we have been asked by the WHO to conduct a formal guideline for the management of COVID-19, which we will perform as data begins to emerge from the clinical trials that are ongoing. All of these proposals, put together, create a suite of approaches to better understanding and managing a new infection. Our team is large and diverse, and has been prepared for this outbreak for a number of years, and are ready to help Canadians respond in an evidence-informed way.",2020,2022,University of British Columbia,716202,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Therapeutics research, development and implementation | Policies for public health, disease control & community resilience",Clinical trial (unspecified trial phase) | Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2020 +C19613,202005VR5,"COVID-19's differential impact on the mental and emotional health of Indigenous Peoples and Newcomers: A socioeconomic analysis of Canada, US and Mexico","Evidence shows that there are economic, and cultural differences in COVID-19 frequency, hospitalization, and mortality (Rodriguez-Lonebear et al., 2020; NYC Health 2020). What is less known is how the restrictions that governments have requested to ""flatten the curve"" may have affected the mental, social and economic health of the population. Recent reports suggest that within populations, there is inequality in how these restrictions have been experienced. For example, job losses are gendered (UN, 2020; Statistics Canada 2020a) and racialized (NPR 2020). Concentrated outbreaks-in meat packing plants, and in long-term care homes have been reported widely in all three countries (Bragg, 2020, Reuters 2020). Racialized peoples are also overrepresented in industries where COVID-19 infections are more likely such as food service and manufacturing, hospital and long-term care staff (IOM 2020; Block and Dhunna, 2020). Because the virus preys on people in vulnerable situations such as overcrowded housing and work stations, these conditions are frequent among racialized persons, Indigenous persons and newcomers, our project answers two central questions: 1) How have COVID-19 related government imposed regulations differentially influenced the mental health and well-being of Indigenous peoples, racialized persons and immigrants? And 2) to what extent have socioeconomic inequalities faced by Indigenous peoples, racialized persons and immigrants influenced their experience of COVID-19 and its related social and economic restrictions? Given our connected borders and interconnected cultures and people, we argue that success rests upon our ability as a continent to work together to protect one another and eventually eradicate this virus which necessitates the three country comparison of Canada, US and Mexico. This proposal seeks funding to build on an ongoing weekly Socioeconomic impacts of COVID-19 survey involving over 17,500 Canadians and Americans.",2020,2021,University of Manitoba,503499,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada | United States of America | Mexico,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +C19614,202005VR4,CovidFree@Home: Development and validation of a multivariable prediction model of deterioration in patients diagnosed with COVID-19 who are managing at home,"Millions of Canadians are anticipated to be infected with COVID-19 during this pandemic and many more will contract it in ongoing community transmission and/or a possible second wave. The majority of people who test positive for COVID-19 are sent home to isolate. In this population, deterioration of their disease can happen quickly and without warning, and we currently cannot accurately predict the approximately 20% who deteriorate and need hospitalization. From discussions with our patients and patient advisor, we know that people who are isolating at home feel terrified and alone. We need an effective and safe ambulatory care and research strategy for people with COVID-19 isolating at home. We are a team of heath care workers, patients, researchers and computer scientists (WearCOPD.ca; Can-BREATHE.ca) with five years of experience developing and using remote monitoring systems for respiratory disease. We have already built a smartphone application to facilitate the care of people with COVID-19 at home by allowing them to report their symptoms to their physician. With this project, we will expand our system to also include continuous smartwatch-based monitoring of heart rate, respiratory rate, cough, speech and other parameters. Sensor data will provide us with large volumes of objective data and allow us to build accurate real time machine learning models for predicting who needs to go to hospital. We will integrate these models into a dashboard that alerts clinicians of any patients that area getting worse, so that they can be called into hospital. Patients can be reassured that they are being followed thoroughly even though they are at home. Our system will also provide a platform for further research into how to prevent long term sequalae and preserve the health of people with COVID-19 who do not require hospitalization.",2020,2021,"Sunnybrook Research Institute (Toronto, Ontario)",393009,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing | Digital Health,,,Canada,Canada,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Health service delivery",2020 +C19615,202109EG5,COVIH study: COVID-19 burden in HIV infected individuals.,"SARS CoV-2 has rapidly spread across the planet and new mutants emerge which are more transmissible and potentially more resistant to our vaccines. Few data exist on COVID-19 disease and vaccine immune responses in immunocompromised individuals, specifically in people living with HIV (PLWH). So far, studies have yielded contradictory results. Several factors can affect COVID disease and vaccine responses in this population including CD4 cell counts, functional immune deficits, as well as socio-demographic conditions and comorbidities such as premature aging phenotypes. We propose to study in-depth these determinants: 1. We will characterize the prevalence and the evolution of COVID-19 in PLWH using a Montreal cohort of PLWH, and a cohort of individuals infected by SARS CoV-2 (Citadel). 2.We will characterize COVID vaccine immune response in PLWH longitudinally, and we will compare it to vaccine response in the general population using a group of 120 PLWH who have been vaccinated with mRNA Moderna vaccine, and samples from the general population obtained from Hema-Quebec. 3.We will share our results in real-time with public health authorities as well as with the community of PLWH. We will develope and information program (webinars, social media content) directed at specific PLWH populations addressing questions about the disease, vaccination and impact on HIV management. We believe that this work will generate data that will inform public health authorities' decisions on COVID vaccination and care for PLWH.",2021,2022,Centre hospitalier de l'Université de Montréal (CHUM),392630,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Characterisation of vaccine-induced immunity | Communication,2021 +C19616,202111WI2,Data and equity needed to drive post-pandemic recovery in Canada: a Saskatchewan contribution,"During the first weeks days of the global pandemic, people in Saskatchewan watched COVID-19 make its way to the province. In March 2020, residents watched for daily updates on new infections, cases that required hospitalization-and, ultimately death rates-as we sheltered in place under lockdown, experiencing relatively low rates of infection. As of November 2021, during the Delta-driven fourth wave, Saskatchewan is experiencing the highest cases, hospitalizations, and deaths per capita, the health care system pushed beyond capacity. What explains the COVID-19 trajectory in this region? How will residents remember and recover from this global pandemic and apply its lessons to local circumstances, now and in the future? In particular, how did the pandemic-including policies and practices implemented throughout-impact the province's most vulnerable and how do we build better systems to cushion them in the future? Co-led by epidemiologist Nazeem Muhajarine and historian of medicine and T1 Canada Research Chair Erika Dyck, this interdisciplinary, bi-university, community-engaged team aims to document, preserve, understand, and communicate the wider impacts of the pandemic on social issues and public health, focusing on four interrelated areas: mental health, substance use, housing precarity, and food insecurity. Through a justice lens, we will examine how the pandemic has affected health disparities in equity-seeking groups and use that knowledge to recommend strategies to 'build back better,' in Saskatchewan and nationally. This research has immense potential to compel decision-makers to act on their own evidence and apply lessons from the pandemic in rebuilding our systems, programs and services, and community resiliency. Also, a longer-lasting product will be a digital, public archive sister project established to collect and preserve memories, reflections, insights from Saskatchewan residents during COVID-19.",2021,2023,University of Saskatchewan,307776.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Indirect health impacts | Social impacts,2021 +C19617,202111WI3,Deciphering the impact of aging and inflammation on neurocognitive impairments in people with Post-Acute Sequelae of COVID-19 (PASC),"www.cbc.ca/player/play/1970781763780](http://www.cbc.ca/player/play/1970781763780)). It is also unclear to what extent brain damage occurs during acute COVID-19 and its contribution to long term consequences of COVID-19, termed 'long covid' or post-acute sequelae of COVID-19 (PASC). Nonetheless, these brain disabilities can prevent people with PASC from returning to work and regular day-to-day activities together with causing depressed mood, social isolation and increased use of the healthcare system. Our proposed research will examine the fundamental disease mechanisms in the brain during COVID-19 using autopsied brain tissues and a mouse model of COVID-19. In people with PASC, we will study the frequency, severity, types of brain function abnormalities using psychological testing. In addition, we will discover risk factors and signs of brain abnormalities measured in the blood in relation to aging and brain resilience or adaptability that can guide diagnosis and treatments. We are a multidisciplinary team and are comprised of early, mid, and senior clinical and experimental researchers with unique expertise in Canada. In fact, our preliminary data show marked inflammation in the brains of humans dying with COVID-19. These proposed studies will discover the disease pathways that cause the brain function abnormalities in people with PASC and will lead to a better understanding of PASC-associated brain problems and new treatment approaches.",2021,2023,University of Alberta,393435.8,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C19618,202111WI4,Demystifying the 'black box' of prisoner re-entry and addressing the mental health and substance use needs and service disruptions for people released from custody during the COVID-19 pandemic,"People released from correctional facilities face significant mental health and addiction challenges, in addition to poverty, homelessness, poor physical health, and discrimination. The COVID-19 pandemic has made community reentry, including access to mental health and substance use services, more difficult. Particularly affected are Indigenous, African, Caribbean, Black, and 2SLGBTQQIA+ persons, who are over-represented in the prison system. Leveraging recently collected data from a rapid COVID-19 study that included in-depth qualitative interviews with service providers and people released from correctional facilities, a targeted survey of Ontario-wide service changes, and an Ontario-wide database of service disruptions/adaptations and helpline calls in the COVID-19 service landscape, this project addresses the mental health and addictions needs and service disruptions for justice-involved persons during the pandemic. We will explore the wider impacts of COVID-19 for their well-being and emergent coping strategies. In combination, these datasets enable us to identify effective models of mental health and addiction care for the current pandemic environment and for future emergencies. We will use GBA+ methodology combined with the Medicine Wheel framework to understand disparities that cut across gender/sexual identities, racial groups and Indigenous status. The study is a collaboration of researchers and community service providers and knowledge users who support people who face incarceration. Rapid knowledge generation and mobilization will ensure timely and targeted policy, practice, and care responses to ensure people who have incarceration histories are adequately supported. Findings will identify innovative adaptations within the mental health and addiction sectors that can inform the present and future pandemic plans, preparations, and responses to better address the needs of this population.",2021,2023,Unity Health Toronto,386723.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19619,202002OV3,Design and evaluation of novel inhibitors targeting SARS-CoV-2 polymerase to create lead compounds to develop more effective treatments of COVID-19,"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 produces a key enzyme, nsp12, essential for replicating the viral genome. In combination with the sequence of nsp12 from SARS-CoV-2, previous studies on closely related enzymes from other viruses provide insights into how nsp12 functions. Our analysis indicates how the specific structural features of nsp12 provide new opportunities for creating inhibitors with higher activity and specificity, and thus likely to act as more effective medications for treating COVID-19. Our models of the 3D structures of nsp12 bound to RNA and drugs like remdesivir indicate how existing inhibitor compounds developed to treat other viral diseases could be modified to work more effectively for treating COVID-19. We propose to synthesize a series of modified inhibitors tailored to fit the structure of nsp12 and then test the activity of these inhibitors on purified nsp12 using a previously published assay procedure. The ability of different inhibitors to disrupt the activity of nsp12 will be measured using this assay. The most effective inhibitors will be cocrystallized into a hybrid form of the norovirus polymerase to provide timely structural information about how inhibitors are likely to bind to nsp12. This structural information will help to further refine the design and improvement of the next generation of inhibitors. Promising inhibitors will be passed on to collaborators and the general community to evaluate their effectiveness in cell culture infection models and ultimately in human clinical trials. We expect to synthesize the first series of novel inhibitors within 4-6 months and to be able to evaluate their activity by the end of 2020. Additional structural characterization will take another 4-6 months. Based on this information, a second generation of inhibitors will be prepared and characterized by the end of the 2-year project.",2020,2022,University of Calgary,312000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19620,202005VR5,"Detection and quantitation of SARS-CoV-2 in wastewater to conduct surveillance on burden of community infection, identify outbreaks and support public health decision-making on control measures for transmission of COVID-19","COVID-19 has been sweeping the world for 6 months. The daily report about new cases, associated deaths and recoveries globally are mentally traumatic for everyone. However, the real number of people infected by this new coronavirus (SARS-CoV-2) may be far higher than official reported because current testing positive numbers counts only sick patients but not asymptomatic ones. Asymptomatic person is the most dangerous silent source for community transmission. A modeling study suggested that the virus might simmer around the world, triggering epidemics every few years. Thus, it would be important to predict the next wave of virus, which allows the government and people to be prepared. Recent studies have detected SARS-CoV-2 in stool as well as raw sewage. We also detected this virus in sewage collected from three different wastewater treatment plants (WWTP) in Alberta. It has been proposed that the occurrence and levels of SARS-CoV-2 in sewage will mirror temporal burden of community infection. Therefore, the aim of this study is to develop a reliable method to detect the prevalence of community infection and forecast the next wave of COVID-19 through monitoring SARS-CoV-2 in sewage. This will provide evidences on the presence and levels of virus in our community, when it will possibly flare up causing an outbreak, and when and why our health authorities give an order to applying or relaxing social distancing and masking measures for controlling virus spread. A mathematical model based on the results obtained from this study will be generated to predict the trend of community infection under different conditions. This research brings benefits and knowledge to every Albertan, and also give us a tool and measure against new coronavirus now and in future.",2020,2021,University of Alberta,365894.25,Viruses | Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Environmental stability of pathogen | Disease surveillance & mapping,2020 +C19621,202108VCF,Developing a COVID-19 Vaccination Strategy that Addresses the Needs of People Who Use Drugs in Canada,"Background: People Who Use Drugs (PWUD) have intersecting health and social vulnerabilities that elevate their risk for COVID-19 infection, complications and mortality. It is therefore critical that PWUD are vaccinated to reduce their risks. However, research has suggested that vaccine acceptability ratings are lower than the general population (Iverson et al., 2021) with safety concerns being the most common reason for vaccine hesitancy (Dietze et al., 2021). Objectives: The purpose of this study is to: (1) identify drivers of vaccine hesitancy and approaches to improve vaccine confidence and; (2) to develop national tailored knowledge mobilization and translation products that are for and by PWUD to promote vaccination based on the findings from Objective 1. We will work closely with PWUD and service providers who work with this population to develop these materials. Methods: The study will recruit 100 participants from an existing national sample of PWUD who previously participated in telephone/video interviews about the impact of COVID-19 in May-June 2020. Semi-structured interviews will be used to identify barriers to receiving vaccinations and ways to address barriers. An advisory committee of PWUD, service providers working with PWUD, and the research team will use responses from the interviews to co-create a multi-pronged approach to address vaccine hesitancy among PWUD. The strategy will include the following components: (1) Developing and disseminating vaccine information resources for PWUD; and (2) Providing training tools to service providers working with PWUD to improve conversations about vaccinations.",2021,2023,Centre for Addiction and Mental Health (Toronto),156115.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Communication | Vaccine/Therapeutic/ treatment hesitancy | Individual level capacity strengthening,2021 +C19622,202108VCF,Developing a tool kit to build vaccine confidence and ensure equitable COVID-19 vaccination implementation strategies in low-and-middle income countries: a multi-stakeholder implementation science and co-development study,"Strategies for implementing equitable vaccine programs are needed to build public confidence in COVID-19 vaccination and improving vaccination rate in high-risk and marginalized people. It is particularly important to developing countries where politics, logistic challenges, and low vaccination willingness in some groups have slowed down vaccination roll-out. In this proposal, we will take the COVID-19 vaccination roll out in the Philippines as an example to identify key principles and develop strategies for delivering vaccines to high-risk and marginalized people to build their confidence in vaccination programs and develop a tool kit to guide the implementation of vaccination programs in developing countries. The study design is guided by the health equity implementation framework in four phases: 1) a situational analysis to understand the processes of current COVID-19 vaccination roll out in the Philippines, as well as the barriers and facilitators towards vaccine uptake, 2) developing a tool kit for improving vaccine delivery to high-risk and marginalized people in the Philippines, 3) piloting the tool kit and assessing its feasibility in the Philippines, 4) adapting the tool kit for other low and middle income countries (LMICs). Developed drawing on learnings from COVID-19 vaccination roll out in the Philippines, our user friendly and contextualized tool kits for guiding equitable vaccine delivery will support vaccination programs in LMICs to reach the most vulnerable and build vaccine confidence in communities. This will benefit ongoing vaccine roll-out, future booster vaccination programs, and other novel vaccine delivery programs should they be required.",2021,2023,University of Toronto,157848.32,Human Populations,Asian,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation | Research to inform ethical issues | Policies for public health, disease control & community resilience","Vaccine design and administration | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy",2021 +C19623,202002OV7,Developing integrated guidelines for health care workers in hospital and primary healthcare facilities in response to Covid-19 pandemic in Low- and Middle-Income Countries (LMICs),"The proposal responds to the CIHR call regarding public health responses to the 2019 novel coronavirus (Covid-19) pandemic. We recognise the gap in LMICs where there is an under financed health system and low capacity of health care workers (HCWs) in hospitals, public and private primary care facilities and the community/ NGO to respond to the pandemic. The World Health Organization (WHO) has produced technical guidance, but the guidance documents are broad, they have to be updated with new developments, and translated into guidelines for HCWs, i.e., doctors, nurses and community health workers for hospitals, primary care and community in LMICs. Here we choose the Philippines and Sri Lanka because they both reported Covid-19 cases, and we can quickly mobilize resources. We aim to develop an integrated plan for HCWs to respond to the pandemic, as well as role-specific guidelines to manage Covid-19 suspects and cases regarding hospital patient flow, infection control, patient supervision and support in communities. We will learn from frontline experiences in China and update our understanding. We will work with policymakers, HCWs and NGOs in the Philippines and Sri Lanka to develop the guidelines and training modules. We will pilot test the tools for feasibility and acceptability among HCWs in the Philippines, adapt in Sri Lanka, and generate a generic version for LMICs to respond to Covid-19 and any future similar pandemic. Our integrated response strategy aims to update skills of HCWs, reduce patient overload at hospitals, avoid hospital transmission, reduce community transmission and public panic, provide patient support and reduce stigma. Our professional team consists of researchers from Canada, the Philippines, and Sri Lanka. The team has strong related experience and can quickly produce a draft guideline and materials within 2 months and finalize all work in 24 months.",2020,2022,University of Toronto,0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | South-East Asia | Western Pacific,,,,Canada,Canada | Sri Lanka | China,Health Systems Research,Health workforce,2020 +C19624,202002OV3,Development and Evaluation of SARS-CoV-2 RNA Polymerase Inhibitors,"Coronaviruses (CoV) can cause severe human respiratory diseases, which is documented by three major outbreaks over the past 17 years: SARS-CoV in 2003, MERS-CoV in 2012, and currently SARS-CoV-2. In response to the current COVID-19 outbreak caused by SARS-CoV-2, we propose to develop novel tools to discover, develop and evaluate inhibitors of the viral polymerase. The polymerase is an enzyme that is essentially required for the propagation of SARS-CoV-2, which makes it an attractive target for therapeutic intervention strategies.",2020,2022,University of Alberta,506250,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19625,202002OV1,Development and implementation of rapid metagenomic sequencing coupled with isothermal amplification point of care testing for viral diagnostics,"Infectious pandemics or plagues have altered human history since the beginning of time. Today we face the threat of viral pandemics spreading through human populations disseminated fueled by the ease of international travel which has become commonplace. SARS, influenza, and now the 2109 novel coronavirus are examples of just a few of these pandemics. We must create novel tools that enable us to rapidly identify the virus and then develop a test that can reliably test for the virus in patients. The test has to be portable and taken to the bedside where patients are quarantined so that these individuals do not further transmit viruses in our hospitals and public places.",2020,2022,University of Calgary,0,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19626,202005VR2,Development of a Microwave Enabled Bio-Nano-Microfluidic Device for Point-of-Care Diagnosis of COVID-19,"The COVID-19 crisis has caused over 280k deaths with more than 4 million infections as of May 8, 2020. These numbers are increasing and may peak again with reopening of businesses. This tragedy could be prevented from happening or its impact could be largely minimized if rapid, massive-scale testing can be performed at community level without the need of highly trained professionals and expensive equipment. This is also the highly recommended action among the immediate next steps by World Health Organization (WHO). The proposed project aims to develop such a system for rapid point-of-care (POC) diagnosis of the COVID-19 virus by leveraging the team's expertise in engineering, nanotechnology, viral immunology and clinical medicine. The proposed system is a palm-sized instrument that consists of a battery-powered microwave circuitry and a microwave-microfluidic device with its sensor surface modified by functionalized gold nanoparticles (gNPs) that specifically recognize the COVID-19 virus. The output is a yes/no answer via a light indicator. A test can be done within 30 minutes including the sample preparation, which is completed by simply stirring a nasopharyngeal swab containing a tested person's sample in a buffer solution. The system allows a test to be completed with a small drop of the sample solution (5 microliter) that is filled in the inlet reservoir and drawn to pass the detection chamber towards the outlet by capillary force. If the sample contains the COVID-19 virus, the virus will be captured by the functionalized gNPs coated on the sensor surface resulting in the change in the microwave spectrum. The microwave circuitry will analyze the spectrum and output a yes/no answer. It is expected that the availability of the proposed portable system will enable the test of COVID-19 at the community level such as at a drive-through point or in an ambulance, which will largely expand the testing capacity and thus assist in the control the COVID-19 pandemic.",2020,2021,University of Waterloo (Ontario),198681,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19627,202002OV5,Development of a nanoparticle-based vaccine candidate to the SARS-CoV-2,"The recent outbreak of the coronavirus in the province of Wuhan in China is an international concern since there is a risk for spreading the infection outside the Chinese territory. The spreading of the virus is facilitated by its human to human transmission by aerosols. Several approaches must be taken to limit the spread of the virus, including quarantine, the decontamination of infected areas, early detection in patients, etc. It is also widely recognized that vaccination is from far the most efficient approach to control the spreading of the infection and protect the population. We propose first the development of a vaccine component-1 to the SARS-CoV-2 based on the use of an immune enhancer nanoparticle coupled to peptides derived from the virus nucleocapsid. This vaccine will trigger a protective immune response against the virus. The use of peptide antigens allows moving very fast in the development of the vaccine candidate. Besides the speed, this approach has the merit to induce a broad CTL immune response that should also trigger protection to any strains of the virus that are related to the first invading coronavirus, like the SARS virus of 2002. Second, we will design and prepare a second vaccine component that will elicit the production of neutralizing antibodies to the SARS-CoV-2. Finally, both components will be combined in one vaccine formulation that will provide robust protection to the SARS-CoV-2 and also to related viruses, like the SRAS virus of 2002. The nanoparticles used to attach the vaccine antigens are very stable. The coupling to the nanoparticle will stabilize the antigens and generate a very stable vaccine formulation that can be stockpiled for a long period (years) without loss of integrity. This is an advantage because to insure preparedness to other epidemics with related viruses.",2020,2022,Université Laval,538233.75,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19628,202002OV5,Development of a novel DC-targeting vaccine that targets COVID-19 spike protein to control COVID-19 infection,"COVID-19 is a coronavirus identified as the cause of an outbreak of respiratory illness that was first detected in Wuhan, China. There is currently no vaccine to prevent COVID-19 infection. The spike protein (SP) of the virus is the key molecule for entry into a cell and is a main target of host protective immune responses. A receptor-binding domain (RBD) located in SP is essential for the infection of COVID-19. Previous studies have demonstrated that RBD of SARS-CoV consists of multiple neutralizing epitopes that induce highly potent neutralizing antibodies. The neutralizing antibody can bind to SARS-CoV and interferes with its ability to infect a cell. These findings suggest that RBD of COVID-19 is an ideal anti-COVID-19 vaccine candidate. Dendritic cells (DCs) are antigen-presenting cells that play critical roles to efficiently present viral antigens to the T cells of the immune system. Therefore, targeting DCs is a promising strategy to improve vaccine effectiveness. Recently, we have developed a highly efficient DC-targeted vaccination technology, and in this study, we will use this vaccination technology to expose the RBD of COVID-19 to host immune system. We will also investigate the potential of this novel vaccine approach to elicit potent immune responses against COVID-19 and SARS-CoV infections in vivo. The success of this proposed study will lay the groundwork for the quick development and production of anti-COVID-19 vaccine candidates, and contribute to a rapid response towards controlling the COVID-19 pandemic in China and worldwide",2020,2022,University of Manitoba,244933.5,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +C19629,202002OV1,Development of a portable point-of-care device for rapid testing of SARS-CoV-2,"The novel coronavirus (SARS-CoV-2) outbreak that started in December 2019 triggered unprecedented measures to avoid a global pandemic. However, China has been particularly hit with over 70 000 confirmed cases, of which about 80% are in Hubei province. Wuhan, capital city of Hubei, is considered ground zero of the outbreak. Testing is typically performed at centralized facilities with highly qualified personnel operating specialized equipment, RT-qPCR being the current method of choice and DNA sequencing a second choice. The response time between sampling patients and obtaining clinically relevant information usually depends on sample shipping time and clinical lab capacity. In this current outbreak containment situation in China, large portions of the population are quarantined, travel is restricted, and clinical labs are operating well over capacity. We propose to develop a rapid point-of-care test to help mitigate the outbreak of COVID-19. The RNA-based test will be performed with a high sensitivity, label-free sensing method. RNA purification and amplification will not be required. The instrumentation needed will be portable and lightweight to enable frontline workers to rapidly test for SARS-CoV-2. The assay will be developed with an easy-to-use platform that can be operated by untrained personnel. It can thereby be deployed locally, within regions of quarantine at a temporary health centers and neighbourhood clinics, reducing flow of people in urban centers; it can be shipped and used in remote or isolated areas including cruise ships",2020,2022,Université Laval,750000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19630,202002OV1,Development of a rapid point-of-care diagnostic test for COVID-19,"A novel zoonotic coronavirus (SARS-CoV-2) has recently been identified in patients with an acute and potentially fatal respiratory disease (COVID-19). This virus is genetically similar to SARS and MERS coronaviruses. The outbreak started in the city of Wuhan (China) and then soon turned into a pandemic with over 60,000 clinical cases and at least 1,500 fatalities. Cases in healthcare workers and other close contacts indicate human-to-human transmission. Rapid, simple and specific point-of-care diagnostic tests are urgently needed for the quick isolation of those infected. To address the issue, we have assembled a team of specialists in chemistry, infectious diseases, and clinical diagnostics. We propose to develop rapid point-of-care tests based on aptamer-assisted graphene oxide (AptaGO) and paper enzyme-linked aptamer assays (p-ELAA) for SARS-CoV-2 and its surrogate (HCoV-229E), which is a Containment Level 2 (CL-2) pathogen. The aptamer-based sensors can rapidly (",2020,2021,University of Ottawa,298500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19631,202002OV3,Development of COVID-2019 main protease inhibitors as potential antivirals against the 2019 coronavirus.,"Coronaviruses are associated with a variety of human diseases ranging from the common cold to new and serious conditions such as Severe Acute Respiratory Syndrome (SARS), which emerged in 2002, Middle Eastern Respiratory Syndrome (MERS), first reported in 2012, and a recent and still growing outbreak of COVID-19, caused by the coronavirus SARS-CoV-2. MERS and SARS together claimed over 1600 lives, and the death toll of COVID-19 recently passed 1300 and is growing rapidly. It is currently unclear if the COVID-19 outbreak can be contained, with some estimates of potential fatalities reaching as high as 50 million. There is currently no approved treatment for any coronavirus, although clinical trials of the Gilead compound Remdesivir are currently underway and there is some optimism that it may be effective against SARS-CoV-2. Nevertheless, there is an urgent need for additional potential SARS-CoV-2 therapeutics, as the success of Remdesivir is far from assured. We are proposing to use a combination of computer calculations and laboratory testing to rapidly identify and validate molecules that block an enzyme that is essential to the virus. The targeted enzyme, known as 3CLpro, is responsible for processing viral proteins into their active forms. A detailed 3D structure of the SARS-CoV-2 3CLpro enzyme was recently solved, and this provides enough information to identify chemical structures of molecules that are likely to block its action, through a procedure known as virtual screening. We will synthesize promising compounds and test them against the purified enzyme using a technique known as Isothermal Titration Calorimetry (ITC). Our team has a proven track record of using virtual screening and ITC to generate potent inhibitors of enzymes similar to 3CLpro. Molecules we identify are likely to prevent the virus from replicating and would have high value as new potential treatments for COVID-19 that could be used alone or in combination with other therapies",2020,2021,McGill University,152250,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19632,202005VR1,Development of safe and effective vaccines against COVID-19,"The current COVID-19 pandemic is a worldwide threat. Moreover, the ability of asymptomatic carriers to transmit the disease is making it very difficult to contain and control. As such, safe and effective vaccines against COVID-19 are urgently needed. The goal of this research project is to develop effective vaccines to combat COVID-19. Combining our expertise in coronaviruses, vaccine development and viral vector engineering, we plan to take novel approaches to develop highly effective vaccines against COVID-19. We will use a helper-dependent adenoviral (HD-Ad) vector to deliver antigens and we will also generate a bacterium-based BCG-COVID-19 compound vaccine. The HD-Ad vectors that we will use offer several advantages over the conventional Ad vectors: 1) they are safer for human use and potent in the delivery of specific antigens, 2) they have a large DNA carrying capacity for expressing multiple antigen genes without the expression of non-specific antigens from the vector and 3) they produce antigens in their native folded form with proper glycosylation and may not require boosting. BCG is an attenuated bacterium and the approved vaccine against tuberculosis in humans. In addition to its specific immune protection against TB, BCG has non-specific benefits as it prevents about 30% of infections with pathogens including viruses. We will construct a recombinant BCG that secretes a fusion protein composed of the bacterial protein antigen 85A fused to the SARS-CoV-2 RBD. This recombinant vaccine will not only retain BCG's nonspecific anti-viral benefits but will also produce specific immune protection against COVID-19. The success of this project will allow us to proceed with the production of the clinical grade vaccines for further testing clinically more than one vaccines while establishing a collaboration with a Canadian biotech that can oversee the licensing and large-scale production of this vaccine for the Canadian market.",2020,2021,University of Toronto,312362.25,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19633,202005VR2,Development of SARS-CoV-2 Peptide Therapeutics and Point-of-Care Salivary Diagnostics for Rapid Viral Detection,"SARS-CoV-2 (the causative agent of COVID-19) poses a generational threat, with no licensed vaccines or effective therapies to date. Further, the scarcity in reliable diagnostics, especially when testing asymptomatic/mildly symptomatic cases, is of grave concern. Accordingly, our proposal tackles 2 of the 3 research areas of this call, and addresses all 5 objectives, by developing and testing SARS-CoV-2 therapeutics and also prototyping convenient point-of-care (POC) COVID-19 diagnostics with scaling-up feasibility. For the therapeutic arm, we will innovatively design and test peptide disruptors of the SARS-CoV-2 spike (S) glycoprotein interaction with the human ACE2 receptor during viral entry, and other peptide inhibitors of viral-human interactions required for SARS-CoV-2 establishment. These will be tested in vitro using cell-based assays, with promising disruptors validated in SARS-CoV-2 hamster models. In addition, we will screen our in-house synthetic compounds targeting chaperones as potential SARS-CoV-2 replication inhibitors in both cell-based assays and animal models. On the diagnostic front, we will develop new diagnostic solutions for effective detection of even mild/asymptomatic SARS-CoV-2 carriers at home and/or in remote locations. This POC lab-on-a tip technology will specifically detect SARS-CoV-2 peptides from patient saliva, with our clinician collaborators taking the lead in scaling-up both peptide therapeutics and our POC diagnostic device through ongoing coordination with the federal government and Saskatchewan Health Authority. This proposal brings together leading Canadian scientists and clinicians to fulfill our objectives by generating high-quality data to diagnostically and therapeutically accelerate the detection and prevention of COVID-19 and foster nationwide collaborations, with a clear scaling-up path that will refine decision-making across Canadian jurisdictions for effective and timely containment of the COVID-19 outbreak.",2020,2021,University of Regina (Saskatchewan),703462.5,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +C19634,202005VR3,Development of small interfering RNAs (siRNAs) for the treatment of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2),"SARS-CoV-2 is responsible for the current coronavirus disease 2019 (COVID-19) pandemic for which there are no treatments yet available. We propose to rapidly design and test several drugs that could be delivered intranasally to treat SARS-CoV-2. We will also analyze the immune response to the virus in patient cells to determine a possible correlation between the early response and the outcome of the disease. The technology we will use is called RNA interference and it works by using what are called small interfering RNAs (siRNAs). siRNAs can direct a person's existing RNA interference machinery to attack any harmful RNA sequence such as the RNA genome of SARS-CoV-2. Furthermore, by reducing the viral burden, siRNAs could contribute to mounting a patient's natural immune response to the virus. We will also design siRNAs to target any factor that would prevent the immune response in the early phase of the disease. siRNAs are easy to design, manufacture and are stable for long-term storage and transport. An advantage for their use as therapy for respiratory infections is that they remain in the lungs when administered intranasally and therefore have low potential to cause side-effects in other parts of the body. We expect that from our project we will identify a safe and effective treatment that could be used in the fight against the current pandemic and future outbreaks of related coronaviruses.",2020,2021,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,270282.75,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C19635,202002OV5,"Development of vaccine candidates and monoclonal antibodies to interrupt the spread of the novel coronavirus, COVID-19.","The novel coronavirus (Covid19) that emerged in Wuhan, China is a threat to global health. Infection causes respiratory disease that can progress to pneumonia, acute respiratory distress and even death. Often patients require hospitalization and intensive care, which increases the chance of viral spread within health care settings. Since it was first identified there have been over 69000 cases, and 1600 deaths, and the virus has spread to multiple countries. Currently, there are no vaccines or therapeutics, but these are urgently needed to bring the epidemic under control. Our proposal seeks to address these areas of need by a multifaceted approach. Specifically, the objectives of this proposal include: 1) Isolation of virus and generation of an in vitro reverse-genetics COVID-19 system 2) Identification of neutralizing antibodies 3) Development and evaluation of candidate vaccines Additionally, the project will generate data on the safety of candidate vaccines in humans through a phase I trial. This will help determine which vaccines can be advance for further study. This will be accomplished through synergistic research between the biotechnology companies Medicago and Inovio in conjunction with several academic research laboratories. Dr. Kobinger's group has an established track record of translational research, and has successfully brought a DNA-vaccine against MERS-CoV to phase I clinical trials 24 months after commencing the project and in less than 7 months for Zika virus. He has led multinational collaborations in the past, and has a history of promoting collaborative and transparent consortium-based research programs. This proposal will develop tools that can be shared with the world scientific community that will help further our understanding of viral pathogenesis, transmission as well as screen potential small-molecule inhibitors and antibodies. Collectively, the findings from this project have potential to contribute to global response against COVID19.",2020,2022,Université Laval,749517,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies | Phase 1 clinical trial,2020 +C19636,202005VR1,Development of Vaccines to Prevent SARS-CoV-2 Infection of High Risk Individuals,"The physical-distancing strategy currently implemented in the Covid-19 pandemic in Canada has been very effective in preventing the vast majority of Canadians from being infected by SARS-CoV-2. This essential short-term strategy is saving lives, but paradoxically will leave most of our citizens without protective immunity and a recurrent outbreak is both predictable and likely without an effective Canadian vaccine strategy. A global effort has been initiated to identify an effective Covid-19 vaccine, testing a variety of vaccine platforms and strategies. Unfortunately, few of these are being developed, tested or manufactured in Canada leaving our population in a very perilous situation where our vaccine needs could be de-prioritized by foreign governments. This project is aimed at bringing together a multi-disciplinary team of scientists and clinicians to rapidly create and manufacture a vaccine to prevent a second wave of infections. We are using scientists and infrastructure, already available in Ottawa, Montreal, Calgary and the US (Covington Louisiana) to rapidly create, compare and contrast different vaccine strategies in animal models. Our best candidate will then be manufactured in a pure enough form to inject in humans. We will complete all of the data and regulatory documents to prepare an application to Health Canada to allow the initiation of a clinical trial in healthy volunteers.",2020,2021,Ottawa Hospital Research Institute,1452112.5,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19637,202108VCF,"Development, Implementation and Evaluation of a Vaccine Confidence Digital App for Young Adults","Young adults (aged 18 to 29 years) have had the highest proportion of COVID-19 cases during the pandemic. At the same time, they are also the adult age group with the highest proportion of those unvaccinated. National and provincial public health leaders have identified young adults as having the highest risk of transmission given their employment in public-facing jobs, social mobility and confined housing. In order to improve vaccination rates, we need to understand reasons why young adults may not be getting vaccinated and use this information to develop and implement vaccination interventions for this age group. This proposal will work closely with young adults through our Young Adult Advisory Group. Our first aim is to engage up to 30 young adults through interviews to understand their knowledge and attitudes towards vaccination. Our second aim is to further develop, and implement, a mobile app, STOP COVID!, designed to improve vaccine confidence and, ultimately, vaccination. STOP COVID! will be a game-based app aimed at changing behaviour intention (nudging) young adults towards vaccination. Content will be science-based and informed by the findings of the first aim so that STOP COVID! will be tailored to young adults. STOP COVID! will be implemented in restaurants and public transit throughout British Columbia, and promoted through social media. We will evaluate the implementation of STOP COVID! to understand in what context is the app effective, in whom and why. Special attention will be made across a range of genders, ethnicity, education and geography across BC. We anticipate STOP COVID! will improve vaccine confidence and uptake in young adults, and with our public health partners, spread to other provinces in the future.",2021,2023,Simon Fraser University,145144.33,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19638,202111WI3,Diabetes in a time of COVID: Understanding impacts of material deprivation and other social factors on direct and indirect pandemic effects in persons with diabetes,"Diabetes is an 'ambulatory care sensitive condition' because better clinic follow-up lowers the chances of needing to be hospitalized or of dying. People with lower incomes generally have more difficulty accessing health care. We suspect that the drop in clinic services not related to COVID-19 infection has impacted them the most, making them even more susceptible to diabetes complications, like dangerous high's and low's in sugar levels, heart attacks, and strokes. We will see if this is what is happening and try to figure out what we can do about it. We will use a rich data sources from Statistics Canada, the Quebec Statistical Institute, and the Office of National Statistics in England. These link information about age, sex, and ethnicity with income level, diagnoses from clinic visits and hospitalizations, and death registries. The information does not contain names or addresses. We will use diagnosis information to figure out who has diabetes. We will study information on people between 2016 and 2022, dividing this period into before pandemic and during the pandemic periods. We will use mathematical equations to figure out if living in a lower income neighbourhood (a signal for living with a lower income) is related to more diabetes-related hospitalization and death, whether this is worse during the pandemic, and how this is related to having less than two follow-ups per year and/or working in a job that does not have the flexibility of working from home. We will see if these relationships are different between women and men, and for people from different self-reported ethnocultural backgrounds. We will see if the difference by income level widened during the pandemic and whether it widened more in Canada or England. The policy differences between Canada and England will give us the context to discuss any differences and how these should influence policy going forward, as related to income supports, educational opportunities, and health care access.",2021,2023,Research Institute of the McGill University Health Centre (RI-MUHC),395000,Human Populations,Unspecified,Unspecified,Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Europe,,,,Canada,Canada | United Kingdom,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Economic impacts | Health service delivery,2021 +C19639,202111WI2,Disseminating and evaluating 'best practices' that promote healthy lifestyle behaviours and mental wellbeing to mitigate the impact of COVID-19 on elementary school children in disadvantaged communities,"Measures implemented to slow the spread of COVID-19 created a lot of hardship for school-aged children. These measures included closures of schools and orders to stay home for many weeks. Considerable concerns have emerged about the impact of these measures on children's health and wellbeing, which may have long-term consequences. This research builds on a 14-year partnership with a program called APPLE Schools, which delivers a successful intervention to promote healthy living and mental wellbeing to kids from disadvantaged settings and currently operates in 74 elementary schools. APPLE Schools developed innovative easy-to-implement practices to support schools during COVID-19. These practices were designed to promote student healthy living and mental wellbeing to ensure health remained a priority while school communities were faced with challenges. In partnership with APPLE Schools, we have generated an inventory of health promotion practices designed by APPLE Schools in response to COVID-19, and linked these with students' lifestyles and wellbeing to identify the most successful practices in APPLE Schools during COVID-19. We now propose research to develop an online toolkit, and promote its dissemination and uptake in all APPLE Schools and all elementary schools across Alberta. We will emphasize promotion of the toolkit in schools in socioeconomically disadvantaged settings to speed up pandemic recovery and alleviate health inequalities. We will then evaluate the uptake of the toolkit among school principals and teachers, and assess its impact on students' lifestyle behaviours (diet, physical activity, screen time, sleep) and mental wellbeing (mood, feelings) in APPLE Schools and an equal number of non-APPLE schools. This study will yield practical, actionable and scalable solutions that will enhance student supports to mitigate the impact of the pandemic on children's health; reduce health inequalities; and provide a resource for future pandemics or disasters.",2021,2023,Unity Health Toronto,362297.95,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19640,202107UIP,Distinguishing the Impacts of the COVID-19 Pandemic on Canadian Post-Secondary Student Mental Health,"There is a need to assess the impacts of changes and disruptions to support services and programming for Canadian youth pursuing post-secondary education during the COVID-19 pandemic. Canadian youth have been enrolling in post-secondary education programs, including university programs, at increasing rates. Before the pandemic hit, many university students reported high levels of subjective psychological distress. The COVID-19 pandemic exacerbated this already-present risk for distress and mental health problems for post-secondary students. COVID-19 restrictions transformed the delivery of post-secondary education last year. Academic environments were characterized by online delivery of courses, remote learning, and altered and limited access to campus services. The proposed research leverages two ongoing large-scale projects to 1) enhance understanding of the impacts of COVID-19 on post-secondary student mental health; 2) describe university student service use patterns within the altered service delivery context that characterized the 2020/2021 academic year; and 3) identify groups of students who were particularly vulnerable to the impacts of COVID-19 on mental health. The results of the proposed research will be ready for mobilization in time for the 2022/2023 academic year, providing critical information to programming and service providers to develop and direct targeted supports for mental health for those students particularly negatively impacted by COVID-19 disruptions.",2021,2022,Concordia University,79499.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19641,202002OV3,Drug repurposing for the rapid development and evaluation of SARS-CoV-2 antivirals,"The initial symptoms of COVID-19 are fever, shortness of breath and a dry cough. For some patients, the disease progresses to pneumonia as the infection spreads to the lung and leads severe inflammation. These severe symptoms can cause difficulties for the lungs to oxygenate the blood and can lead to death. There are currently no antivirals against SARS-CoV2, the causative agent of COVID-19, and development of new molecules can take years to reach patients. As the COVID-19 epidemic is progressing rapidly, the need for antiviral therapy is urgent. Therefore, our goal is to use our current arsenal of approved drugs already tested for their safety and used in the clinic for various conditions and repurpose them to treat COVID-19. In this rapid response grant, we propose to identify drugs with activity against SARS-CoV2 in vitro and in vivo and contribute to the global COVID-19 response and provide a therapeutic option for patients developing life-threatening disease.",2020,2022,University of Ottawa,311764.5,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19642,202005VR2,Early immune predictors of sustained SARS-CoV-2 antibody responses after COVID-19 disease,"COVID-19, a disease caused by a new Coronavirus, is an unprecedented global health crisis for which we currently have nor safe nor rapid response. Given the absence of vaccines and effective therapies, it is essential to understand the development, effectiveness and maintenance of antiviral responses against its causing agent, the SARS-CoV-2 virus. The highly variable immune response against SARS-CoV-2 define the severity of the disease, but many critical questions remain: 1) can we predict patients that will experience a severe disease and delayed viral clearance? 2) do survivors of COVID-19 develop durable and protective antiviral immunity? 3) can serology identify convalescent COVID-19 patients who are at high risk of re-infection? 4) does re-exposure to the virus boost their antiviral immunity? We propose the creation of a multi-site consortium composed of 12 scientists (6 women and 6 men) with solid expertise in virology and immunology and from leading academic institutions in Quebec (UdeM, IRCM) and the US (Columbia, NY) to study antiviral immunity in COVID-19 in both sexes to address unresolved issues, as outlined in the CIHR call: in Aim 1 and 2, we focus on early clinical and immunological features of COVID-19 that can predict the emergence of protective and durable antibodies. We will compare cohorts of patients enrolled in the ""Biobanque quebecoise de la COVID-19"" (BQC19) that experienced mild or severe COVID-19 or COVID-19-like symptoms attributed to another infectious agent. In Aim 3, we will focus on a cohort of health care worker tending COVID-19 patients, therefore at higher risk of repeat exposure to the virus. Using this cohort, we will study the effect of repeat exposure on immunity boosting against the virus and help define the immunological requirements of a successful vaccine. Taken together, our proposal will provide the immunological perspective needed to better prepare and implement a safe exit from the current public health crisis.",2020,2021,Centre hospitalier de l'Université de Montréal (CHUM),0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease susceptibility | Prognostic factors for disease severity,2020 +C19643,202109EG8,Effectiveness of digital interventions in improving mental health during COVID-19: Evaluation of Wellness Together Canada,"Mental health challenges affect all Canadians. Yet many Canadians lack access to mental health care services, with equity in access a key concern for specific groups due to gender, ethnicity, socio-economic status, geographic isolation, and immigration status issues. The COVID-19 pandemic is exacerbating mental health challenges and widening service gaps, especially among those in marginalized groups and those with pre-existing mental health issues, making it a critical time to provide tools that will improve mental health at the population level. Wellness Together Canada (WTC) was created in response to this unprecedented rise in mental health and substance use concerns due to the COVID-19 pandemic, with funding from the Government of Canada. It is a mental health and substance use website to support people across Canada providing digital interventions and services at no cost. It partners with other digital interventions to be the home portal for access to digital interventions from 1:1 support, peer groups, and self-help tools. However, the effectiveness of this intervention has not been established. This project is required to address one of the crucial elements needed to help Canada address the effects of the pandemic and adjust post pandemic (Research area #9). This proposal will evaluate the impact of use of the Wellness Together on depression and anxiety trajectories among Canadians. We will use integrated knowledge translation throughout all stages and aspects of the program (development, implementation, evaluation) to ensure that the mental health needs of equity seeking groups and other stakeholders are addressed.",2021,2022,Centre for Addiction and Mental Health (Toronto),245058,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19644,202107UIP,Effects of COVID-19 on South Asian Mothers and Families in BC,"Women have been disproportionately affected by the COVID-19 pandemic. Mothers in particular are simultaneously managing paid employment, household work, homeschooling and/or childcare. The impact has been particularly severe for South Asian mothers in Canada, who often experienced further stressors such as language barriers, caring for elderly relatives, and transnational economic and social responsibilities. South Asian women and their family members are often at higher risk for contracting COVID-19 as they are more likely to work in employment sectors with greater exposure to the virus. They have also been more severely affected by job loss during the pandemic as they are over-represented in hard-hit industries such as food and accommodation services. Finally, South Asian women have faced increased racial prejudice, often being falsely blamed for the pandemic, (particularly as the Delta variant, initially inappropriately labelled the ""Indian variant"", quickly became a widespread variant of concern). To date there is limited knowledge on the health, psychosocial and socio-economic impacts of the COVID-19 pandemic on mothers in Canadian South Asian communities, and how these impacts affect their families. We will examine South Asian mothers' COVID-19 experiences (including positive supports) and levels of moral distress using a longitudinal mixed method approach (interviews and questionnaires/surveys). Moral distress is defined as a phenomenon in which a person knows the right action to take, but is constrained from taking it because of barriers beyond their control. The experiences of South Asian mothers during the pandemic potentially contribute to cumulative moral distress. This research will be conducted in the Fraser Health Region of BC. Collaborations with provincial knowledge users and community organization partners will ensure their information needs are met and the resulting recommendations can be readily translated into changes in policy and practice.",2021,2022,University of The Fraser Valley,118500,Human Populations,Asian,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C19645,202111WI3,Effects of COVID-19 on South Asian Mothers and Families in British Columbia,"Women have been disproportionately affected by the COVID-19 pandemic. Mothers in particular are simultaneously managing paid employment, household work, homeschooling and/or childcare. The impact has been particularly severe for South Asian mothers in Canada, who often experienced further stressors such as language barriers, living in multigenerational households, and transnational economic and social responsibilities. South Asian women and their family members are often at higher risk for contracting COVID-19 as they are more likely to work in employment sectors with greater exposure to the virus. They have also been more severely affected by job loss during the pandemic as they are over-represented in hard-hit industries such as food and accommodation services. Finally, South Asian women have faced increased racial prejudice, often being falsely blamed for the pandemic. To date there is limited knowledge on the health, psychosocial and socio-economic impacts of the COVID-19 pandemic on mothers in Canadian South Asian communities, how these impacts affect their families, and what resources and supports facilitated their ability to cope. Guided by an intersectional feminist framework and using a strength-based approach, we will examine the direct and indirect effects of COVID-19 and levels of moral distress in South Asian mothers. Moral distress is defined as knowing the right action to take, but being constrained from taking it because of barriers beyond the individual's control. We will conduct interviews with 20-30 South Asian mothers with dependent children and interviews with 10 community organizations. This research will be conducted in the Fraser Health Region of BC in collaboration with provincial knowledge users and community organization partners. Knowledge translation will include infographic reports of results, community workshops, sharing of stories of 'surviving and thriving' through a booklet and workshops, and workshops for service providers.",2021,2023,University of The Fraser Valley,252126.92,Human Populations,Asian,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C19646,202111WI1,"Endometriosis and chronic pelvic pain: impact of the COVID-19 pandemic on virtual, surgical, and multidisciplinary care","Endometriosis affects ~10% of the population and is a common cause of chronic pelvic pain. It is defined as tissue resembling cells in the uterus (womb), being present outside of the uterus. In this proposal, we will examine the impact of the COVID-19 pandemic on endometriosis and chronic pelvic pain. At our centre during the pandemic, there was incorporation of virtual care, conversion of a multidisciplinary pain program to virtual, and delays in surgical treatment of endometriosis. Our first aim is to the examine how the pandemic and these practice changes impacted patients with endometriosis/chronic pelvic pain, such as pain levels, mental health, quality-of-life, and disease severity. Our second aim is to assess how diagnosis and management of endometriosis/chronic pelvic pain changed with virtual care only, compared to an in-person assessment with physical examination and point-of-care ultrasound, with particular focus on impact on surgical treatment. The third aim is to specifically examine the experiences of patients with endometriosis of East and South-East Asian descent, given the geopolitics of the pandemic and anti-Asian discrimination. We will conduct both quantitative (statistical) analyses and an arts-based study using Photovoice to capture the experiences of these individuals. This research will provide a comprehensive picture of the impact of the COVID-19 pandemic and will have direct implications for quality improvement of the care provided for endometriosis and chronic pelvic pain.",2021,2023,University of British Columbia,395000,Human Populations,Asian,Adults (18 and older),Unspecified,Women | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19647,202107UIP,"Engage, Educate, Empower: Partnering with Canadian Families to Understand and Mitigate the Multifaceted Impacts of the COVID-19 Pandemic on Child and Youth Wellbeing","On March 11, 2020 the World Health Organization declared the novel coronavirus COVID-19 disease a global pandemic. In efforts to keep the public protected, the Canadian government has implemented physical distancing policies and widespread closure of public institutions. However, these measures have had unintentional consequences for Canadian youth, including disruptions to education, intake of misinformation, and increased levels of isolation, stress, and anxiety. Efforts to understand the impact of COVID-19 on youth's experiences, behaviours, and beliefs are needed to improve circumstances, knowledge and trust in this vulnerable population. Our team will address this gap through a national research study that will result in the development of a public education and engagement campaign. This will be achieved in three phases of work: 1) Online surveys with parents and youth to to create a comprehensive list of COVID-19 associated policies and restrictions that most impacted their wellbeing; 2) Interviews with parents and youth to gain a deeper understanding of the major factors (stressors and protective mechanisms) influencing youth wellbeing; 3) development and application of targeted integrated knowledge translation interventions to inform social and public health responses and improve youth and family wellbeing. This study will complement ongoing parallel research in the adult population currently being conducted by our team with the ultimate goal to partner with Canadian youth and families to understand the detrimental and positive impacts of the pandemic and related restrictions on their wellbeing (health, connectedness, safety, learning, agency), and optimize opportunities for recovery and long-term resilience.",2021,2022,Dalhousie University,114357.24,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2021 +C19648,202005VR5,"Engage-COVID-19: A mixed methods study of biomedical, behavioural, and psychosocial aspects of the COVID-19 pandemic among gay, bisexual, and other men who have sex with men in Canada","Gay, bisexual, and other men who have sex with men (GBM) have historically experienced significant disparities in physical, mental, and sexual health, amplified by systemic marginalization and high barriers to healthcare. This context of inequity creates heightened vulnerabilities to COVID-19. Failure to respond to the health and wellness needs of GBM may have significant negative effects on COVID-19 outcomes and exacerbate existing health disparities. We propose the Engage-COVID-19 Study to rapidly respond to current and pressing knowledge gaps concerning the COVID-19 pandemic among GBM in Canada. This study will be embedded within the Engage Cohort Study, which is the only study with comparable biobehavioural data on HIV/STI prevalence and risk behaviours for GBM in Canada. To date, baseline data collection has been completed with 1842 GBM who are enrolled in the Engage Cohort Study (565 in Vancouver, 388 in Toronto, and 889 in Montreal). All of these participants will be invited to have SARS-CoV-2 antibody testing and complete an in-depth survey that will include COVID-specific quantitative questions. We anticipate recruiting a total sample of 1695-1768 participants. In addition, from this group we will recruit 90 GBM participants for qualitative interviews in Vancouver (30), Toronto (30), and Montreal (30) to assess the direct and indirect impacts of COVID-19 on Canadian GBM. These data are necessary both to understand COVID-19 risks, vulnerabilities, and prevention strategies, as well as the impacts of COVID-19 on health service access and different levels of HIV/STI risk across provinces. By making efficient use of available research infrastructure, our proposed study will ascertain the occurrence of COVID-19 by documenting SARS-CoV-2 immunity within both HIV-positive and -negative participants and produce rapid, high-quality evidence for preventing the direct and indirect effects of COVID-19 for this population across multiple jurisdictions.",2020,2021,University of Toronto,435957,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Immunity | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Indirect health impacts,2020 +C19649,202107UIP,Engaging youth and families in designing a mental health service plan in response to the COVID-19 pandemic: A participatory action research study,"Youth are at risk of experiencing poor mental health due to the daily life changes associated with COVID-19 pandemic, and evidence from youth and parents reveals that this is the trend. Data suggest that the pandemic-related changes in youth mental health may lead to more youth accessing services in the future. Therefore, our healthcare system should be ready to meet the needs of youth. However, during the pandemic how, what and to whom services were delivered also changed, namely with the shift to online services. These changes were made quickly and did not involve any input from youth or their families. As society recovers from the pandemic, we need to figure out who to help, what help they need, and how best to offer services that benefit them. Involving youth and families in service planning is the best way to arrive at solutions most acceptable to youth and lead to mental health improvements. In this study, youth and families will be equal members of the research team and will be fully involved in organizing focus groups to (1) Understand what the mental health service needs, preferences and experiences of youth and families are, and (2) Create information for how services can be improved to lead to better outcomes. We aim to include participants with various backgrounds and experiences to improve the diversity and applicability of our findings. This study will involve multiple phases, from determining the research questions to presenting the findings, all of which will be shaped by youth and families, to reflect their interests and needs. What we learn from the focus groups will be used to create tools that can be used by youth and families, health providers, policy makers, and researchers to support the best possible service delivery and mental health outcomes during and after the pandemic. Relationships with mental health organizations will help us to share our findings more widely and promote long-standing changes to mental health care for youth.",2021,2022,Children's Hospital of Eastern Ontario Research Institute Inc,114213.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2021 +C19650,202107UIP,Epigenetic Impacts of COVID-19 Pandemic Chronic Stress on Youth: A Prospective Investigation of DNA methylation,"The COVID-19 pandemic has introduced severe economic and social hardships contributing to rising rates of mental health problems in youth. Described as a ""ticking time bomb"", youth mental health problems have negative consequences for lifelong dysfunction affecting educational achievement, relationship success, work attainment and income. COVID-19 stressors may impact youth mental health by 'getting under the skin' and becoming engrained in child biology. To test this hypothesis, we propose quantifying an epigenetic mark called DNA methylation from child cheek swabs collected serendipitously just prior to the onset of the COVID-19 pandemic for comparison with samples we propose to collect approximately 2 years later. Our analysis first involves the creation of a pandemic stress score representing how much stress each child faced by combining stress measures from child and parent reports at the level of the youth (e.g., infection risks to child and friends), family (e.g., parental conflict), and community (loss of in-person schooling) and validating those scores with concurrent assessments of child mental health (i.e., depression, anxiety). Second, we will test whether pandemic stress scores relate to shifts in biological DNA methylation patterns pre- to 2 years post-pandemic onset, and whether shifts relate to youth mental health outcomes 2 years post-pandemic onset. We will also test whether pandemic stress is related to 'biological age', a DNA methylation-based gauge of biological aging that is relevant for long-term health outcomes. We will do each analysis separately for males and females to identify sex-specific stress pathways, given literature showing sex differences in both stress experiences and mental health outcomes. Findings will inform how pandemic stress from economic strain and social restrictions gets under the skin to affect youth mental health and what biological factors put some children at greater risk than others for mental health consequences.",2021,2022,University of Calgary,118311.19,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19651,202107UIP,Essential and Invisible: Understanding the Needs of and Supporting Young Caregivers and Their Families Through Pandemic Recovery and Beyond Using a National Network,"More than 8 million Canadians provide unpaid care to a family member or friend with injury, disability, or illness. Of these, 1.25 million are young caregivers (those under 25) who care for a sibling(s), parent(s), or grandparent(s) while juggling school and sometimes paid work. Most Canadians are unaware of the responsibilities and challenges faced by these 'invisible' caregivers and they are a severely understudied group in Canada. As a result of COVID, young caregivers and their families may experience a greater impact from experiences such as, but not limited to, unemployment (due to financial strain from caregiving), delayed access to services for their loved ones, and fears of infecting a loved one who is in a high risk category for infection from COVID. This project expands on an ongoing study in Ontario to address knowledge gaps from community service providers in 3 other provinces: Alberta, British Columbia, and Nova Scotia. The study objectives are: 1) to identify the impact of restrictions on young caregivers and their families; 2) how they navigated and responded to these changes/impacts; 3) identify the key factors at the micro-, meso-, and macro- levels that influenced the impact of and how they navigated COVID; 4) explore gender differences in caregiving experience, challenges, and expectations in young caregivers, their parents, and those whom they care for; 5) compare and contrast the experiences of participants living in rural versus urban communities across Canada; 6) to determine the most appropriate and acceptable strategies to support caregiving families and their children; and 7) create and grow a national network throughout this project to allow existing and new network members to use the knowledge created during this study to support their clients and eventually leverage collective action to influence broader change throughout Canada during recovery from COVID and beyond.",2021,2022,Ryerson University,118383.87,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19652,202203MM1,Evaluating a virtual stepped care portal in youth awaiting tertiary chronic pain care: An Implementation-Effectiveness Hybrid Type III study,"Pain is one of the most common symptoms of extreme stress in youth. Without treatment, acute pain will become chronic (CP; pain lasting >3 months), a problem already affecting 1 in 5 Canadian youth. The COVID-19 pandemic is one of the greatest threats to youth mental health seen in generations. CP in childhood can trigger a wave of mental health issues that carry forward into adulthood. In 2019, we learned that ""access to pain care"" is poor and a priority for youth with CP and their families. Unfortunately, COVID-19 has only made access more difficult. In 2020, we created an online ""stepped care"" program called the Power over Pain Portal. Stepped care is a promising way to improve access to CP care by tailoring care based on each person's symptom severity. Like a ladder, a person may start with one type of care and then ""step up"" or ""step down"" to more or less intense care depending on what they need. Over the past year, we worked with hundreds of youth and healthcare professionals across Canada to understand how the pandemic has affected pain and mental health. We also summarized all online pain self-management programs including peer support for youth to find the best resources to include in the Portal. Together with a diverse group of youth, we have now co-designed the online Portal. The next step (focus of this grant) is to test the Portal with youth to ensure it can be implemented well and is helpful. We will also translate the Portal into French. We will recruit 72 youth with CP waiting for specialist care at 11 CP clinics across Canada to use the Portal for 4 months. We will see how they use the Portal and if it helps to improve their pain and mental health. This study is important because it will allow us to understand how the Portal works in the real world before wide public release (English and French) to support all youth in Canada with CP with accessible, evidence-based pain care.",2022,2024,Hospital for Sick Children (Toronto),316614.76,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +C19653,202109ER5,Evaluating pandemic interventions in Indigenous communities (EPIC): A community-based participatory approach to address gaps and build capacity,"Canada's pandemic response to COVID-19 has substantial shortfalls, particularly with protecting the health of Indigenous communities. A significant gap remains regarding the generation and evaluation of local pandemic plans in Indigenous communities as these are not addressed in an Indigenous context in any planning guidelines. While the WHO pandemic guidelines, the CPIP, and the OHP for an Influenza Pandemic provide guidance for developing pandemic plans for the general population, these documents fail to adequately address the needs of marginalised groups, such as Indigenous communities. Public health emergency preparedness is vital to mitigate the impact of pathogens that cause social and economic disruptions, especially in First Nations communities facing structural inequities and lasting impacts of colonization. In remote Indigenous communities, outbreaks have devastating consequences resulting from fly-in-only isolation combined with a community's lack of ability to rapidly provide adequate care and protection. Importantly, within many First Nations communities there are people with diverse health status (e.g., individuals with comorbidities) and represent a younger demographic profile compared to non-Indigenous Canadians. The Evaluating Pandemic Interventions in Indigenous Communities (EPIC) project will evaluate and update pandemic plans in collaboration with members and leaders of two First Nation communities with relevant science-based tools that support capacity building and self-reliance. To address gaps and build capacity for the COVID-19 and future pandemic responses the program will evaluate community-implemented mitigation measures to reduce the impact of COVID-19 on health care systems and services, and improve provided support services. The project will result in revised local pandemic plans that contain learnings which can be transferred to other Indigenous communities and host an international symposium to develop a best-practices framework.",2021,2022,Ryerson University,247953.35,Human Populations,Other,Unspecified,Rural Population/Setting | Urban Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Policy research and interventions,2021 +C19654,202005VR5,"Evaluating the differential impact of what we have done, as we prioritize what to do next: a multi-provincial intervention modeling study using population-based data","In Canada, as elsewhere, the COVID-19 epidemic has spread at varying speeds and amplitudes across people, places, and time. Early model predictions were dire across the board largely because of limited local data. So early models had to assume that we were all at equal risk, regardless of conditions that can lead to differential risks of transmission (e.g. living in shelters or long-term care facilities) and of severe outcomes (e.g. age, health conditions). Thus, an assumption of homogeneity was at the heart of the ""hammer"" part of the public health response. Public health measures (interventions) also varied between provinces. As we enter the ""dance"" phase and prepare for future waves of the epidemic, we have an opportunity to be more specific with our interventions if we can quickly learn from how well our public health measures worked or did not work for different subgroups and between provinces, using the wealth of data now available. Our team will use an integrated surveillance and health-administrative data infrastructure and mathematical models that were built over the last 2 months in Quebec, Ontario, Manitoba, Alberta, and British Columbia to answer the following questions: 1. Who, where, when, and under what conditions are subsets of the population most at risk? 2. What led to differences in the trajectory and size of COVID-19 sub-epidemics within and between provinces? 3. What types of population- and facility-specific strategies that could stop these sub-epidemics and prevent their re-emergence, while allowing us to relax universal physical distancing measures? Our team of epidemiologists, mathematical modelers, statisticians, clinicians, microbiologists, and public health officials will work together to rapidly provide answers in way that embraces data-driven heterogeneity in risks so that we can better inform decisions on what to implement, when, for whom, and for how long, to minimize the need for universal stay-at-home strategies.",2020,2021,Unity Health Toronto,970223.25,Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +C19655,202111WI1,Evaluating the impact of the COVID-19 pandemic on cancer control in Manitoba,"Cancer is the leading cause of death in Canada. The cancer care system aims to lessen this burden by improving survival through screening, early detection and diagnosis, and timely, high quality treatment. However, the COVID-19 pandemic has had a significant impact on cancer care. In Manitoba, several interventions were implemented by CancerCare Manitoba (CCMB) (the provincial agency responsible for cancer screening and treatment) to keep cancer patients safe while continuing to provide excellent care. These interventions included changes to cancer screening programs, shifts from in-person visits to telephone visits, prioritizing the most critical cancer surgeries, and altering how chemotherapy and radiotherapy were delivered. The overall goal of this project is to understand how the COVID-19 pandemic and the interventions that were implemented to reduce its impact affected cancer services and outcomes such as survival in Manitoba.",2021,2023,University of Manitoba,347119.68,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19656,202109EG1,"Evaluating the Peel Community Health Ambassador Program: Building trusting, equitable, and responsive healthcare during the COVID-19 pandemic","The Peel region of Ontario has experienced one of the highest positivity rates for COVID-19 across Canada. Individuals and families from Peel's diverse communities have experienced negative impacts to their overall health and well-being including barriers to accessing care, psychological stress, trauma and poor mental health, lack of physical activity, and social isolation. Data collected throughout the pandemic show that certain communities have been disproportionately impacted by COVID-19 based on race, immigration, gender, housing, and employment. In response to the structural inequalities and barriers that have impacted COVID-19 testing and vaccination, the Community Health Ambassador (CHA) Program was developed and implemented in high priority communities in Peel through Ontario's High Priority Communities Strategy. Starting in January 2021 and implemented through six community agencies, the purpose of the CHA Program was to provide culturally specific community outreach, education, and support during the COVID-19 pandemic. Through partnership between community agencies, healthcare workers, researchers, Community Health Ambassadors, and community members in Peel, this mixed methods evaluation of the CHA Program will fill a critical research gap and yield timely, high-quality, and relevant evidence about how communities can respond effectively to the ongoing pandemic and minimize the direct and indirect impacts on people who identify from racialized communities experiencing structural inequalities. These findings will be valuable for diverse communities experiencing disproportionate impacts of COVID-19 across Canada and globally.",2021,2022,"Trillium Health Partners (Mississauga, ON)",170948.89,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Social impacts | Health service delivery,2021 +C19657,202109EG7,Evidence-based interventions to address social anxiety disorder during COVID-19.,"Social anxiety disorder (SAD), the fear of social situations, is one of the most common and disabling anxiety disorders in Canada, which is associated with reduced functioning, isolation, depression and suicidal ideation. COVID-19 may have led to the persistence and eventual worsening of SAD as the opportunities for exposure to social interactions and access to health services were decreased. Further, deconfinement announcements may lead to worsening of symptoms. With anxiety on the rise in Canada, and more so in underserved and at-risk groups due to the differential impacts of COVID-19 and pre-existing social and health inequities, mental health service needs are increasing. Cognitive behavioural therapy (CBT) is the most evidence-based treatment for SAD. With the move towards telehealth, it is reassuring that studies also show the effectiveness of CBT offered virtually for anxiety disorders. The Shyness Programme internet-delivered CBT (iCBT) for SAD was developed in Australia in 2008 and is available in English. We aim to 1) adapt the iCBT Shyness Program to the Canadian context, by conducting a French and English adaptation in Quebec and in Ontario to account for the preferences of racialized persons, socio-cultural, and linguistic minority groups; 2) examine the adapted program's effectiveness; and 3) explore barriers and facilitating factors, including acceptability (e.g., among socio-cultural groups), to its implementation. The study will be carried out in community-based primary health care in Quebec and Ontario. Participants with SAD will self-refer or be prescribed iCBT. The program will be implemented via a virtual clinic at U de Sherbrooke. The trial outcomes will provide important evidence-based data to support the implementation and adoption of a Canadian adapted iCBT program, information useful for the scale-up of the intervention in Canada to improve the mental health of underserved populations with SAD and timely access to low-intensity iCBT.",2021,2022,Université de Sherbrooke,533657.64,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19658,202111WI2,Examining an inclusive economic approach to improving health outcomes for diverse populations within the context of the COVID-19 pandemic,"The COVID-19 pandemic has inequitably impacted Canada's workforce and economy, disproportionately harming the health of those marginalized along lines of race, class, gender, age, ability, and sexuality. Inclusive economic strategies-a promising approach to equitable economic recovery-strive to raise living standards and create prosperity for all people (e.g., targeted ""good job"" creation for disadvantaged communities). EndPovertyEdmonton (EPE) is an organization convening agencies and companies using inclusive economic strategies. However, these agencies and companies report challenges to their implementation, like language barriers and discrimination. While EPE intervenes on multiple levels with government and industry, it is unclear which strategies lead to recruiting and retaining diverse people into good jobs (e.g., jobs providing living wages and benefits) and whether these jobs improve health. We will ask three questions: 1) how are inclusive economic strategies implemented to improve health outcomes for diverse populations within the COVID-19 context? 2) how do these strategies affect health outcomes for diverse populations? 3) how has the pandemic affected workers' perspectives regarding employment and their health? We will use qualitative and quantitative methods (interviews, surveys, participant observation, document review). Data will be collected with two groups: 1) staff at EPE and partnering agencies and companies implementing inclusive economic strategies; and 2) diverse workers (e.g., newcomers, women, LGBTQQIP2SAA). Methods include following a cohort of diverse workers who have been hired, trained, and retained in good jobs to assess effects on health outcomes (stress, quality of life, self-rated health) over time. EPE and partnering agencies and companies will be involved in interpreting findings, which will be shared as actionable information about how economic systems can be transformed to respond to systemic inadequacies exposed by COVID-19.",2021,2023,University of Alberta,288114.58,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C19659,202107UIP,"Examining the effects of public health policies implemented during the COVID-19 pandemic on unintentional injuries in children and youth in British Columbia and Ontario, including as related to equity and marginalized populations","Although stay-at-home orders and other measures during pandemics are implemented to protect the population, a serious consequence of quarantine has been a change in the patterns of unintentional injuries among children and youth, with increases seen particularly at home, during some outdoor play and recreational activities such as swimming, and on the road such as cycling. During the height of the pandemic, public health leaders and governments required Canadians to stay-at-home and to maintain 6 feet apart if, and when, they were out. These policies, and the response to them, undoubtedly saved lives. We are unsure however, of how some COVID-19 policies may have affected other health outcomes. A recent Children First Canada report called, ""Raising Canada 2020"" reported that it is unknown if and how COVID-19 policies have had an effect on children and youth in terms of unintentional injury. Preventable injury is the number one threat to children and youth in Canada. Despite this, we do not have data on the number of children and youth affected by unintentional injury during the COVID-19 restrictions. Our research project will use several sources of data to better understand how many children and youth were injured during the pandemic. We will use data to report on the type of injuries that occurred and how, so that this information can inform us of what to do to prevent this from happening in the future.",2021,2022,University of British Columbia,111348.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19660,202111WI3,Examining the impact of COVID-19 on acute episodes of care and health care utilization among persons with spinal cord injury: A population-based administrative health data study,"The COVID-19 pandemic has impacted the provision of healthcare services, making it harder for some people, especially those with more complex health and social needs, to access the care they need. People living with spinal cord injury or dysfunction typically require frequent visits to their healthcare providers for regular surveillance of secondary complications related to their condition, in addition to addressing other health problems as they arise. Our proposed research has two key goals. First, we will examine the patterns of healthcare use by people in Ontario with spinal cord injury or dysfunction before and after the outbreak of the COVID-19 pandemic. Second, will look at the experience of people living in the community with a longstanding injury, looking at possible disruptions to their routine preventive care. We will also study newly injured people who are transitioning from acute hospital care through rehabilitation and back to the community, looking in particular at the length of time they spend in hospital and their number of transfers between different health care facilities. These findings will inform how populations with multi-morbidity and disability, such as those with spinal cord injury or dysfunction, were impacted by service delivery and policy changes.",2021,2023,University of Toronto,168657.1,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19661,202111WI2,Examining the impact of young children's digital media use during the COVID-19 pandemic on health and developmental outcomes: A comprehensive assessment to inform harm-reduction and positive digital media use strategies,"Digital media use by young children rose during the pandemic. Too much time spent in front of screens by preschoolers has been linked to adverse health and developmental outcomes in later childhood. However, digital media use by young children can also benefit cognitive and psychosocial outcomes under the right circumstances. To inform harm-reduction interventions, a nuanced understanding of the impact of digital media on children is needed. As such, the present project considers digital media usage comprehensively by considering context (ex., viewing alone vs coviewing), function (ex., passive viewing vs video chatting), and content (ex., educational vs violent) in addition to the duration of usage. The main objective of this research is to examine how digital media use during the pandemic contributes to child health, and developmental outcomes at the time of school entry. More specifically, Aim 1 is to examine how child media use contributes to direct assessments of health (ex., BMI, physical activity), and physical (ex., motor skills), cognitive (i.e., language, memory) and psychosocial (i.e., emotional regulation) outcomes. Aim 2 is to estimate associations between media use and academic outcomes at school entry (i.e., grades, classroom engagement). Finally, Aim 3 addresses the extent to which child (i.e., sex, temperament) and family (i.e., SES, parenting stress) characteristics contribute to child digital media habits. The extent to which these characteristics amplify/buffer the consequences of child media use will also be considered. Aims will be met by assessing child health, physical, cognitive, psychosocial, and academic outcomes from a pre-existing sample of Canadian children (N=331, mean age= 6.46, in summer 2022) assessed twice previously during the pandemic in 2020 (mean age= 3.5) and 2021 (mean age=4.5). Preexisting data include child and family characteristics, and comprehensive assessments of media use duration, content, context, and function.",2021,2023,Université de Sherbrooke,386702.63,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19662,202111WI3,Examining the Impacts of the COVID-19 Pandemic on Iraqi Refugees in Canada,"Our research will explore the extent and impact of the indirect and wider health consequences of the COVID-19 pandemic and the resilience of recent refugees in Canada. We will provide recommendations for effective policy interventions for the pandemic's broader impacts, which will improve preparedness for future health emergencies and pandemics. Our research will generate evidence related to refugees in Canada from war-torn countries. In what the United Nations has called the biggest civilian displacement catastrophe in the 20th and 21st centuries, 2.5 million Iraqi civilians, including the majority of the educated middle class, have sought refuge in other countries, including Canada. Between 2003 and 2018, Canada resettled 37000 Iraqi refugees displaced in Syria, Jordan, Lebanon, and Turkey. Our study focuses on Iraqi refugees who arrived in Canada between 2015-2021. We will study how existing disparities such as exacerbated poverty and food insecurity, access to health and social services, and systemic racism among the Iraqi refugee population in Canada have changed since the beginning of the pandemic. Our project will consider a lifecycle approach and examine the pandemic impacts on older populations, infants, children and youth from Iraqi refugee populations. London, Ontario, is one of the major urban centres in Canada in which the federal government provides settlement and resettlement services for Iraqi refugees. We have developed a formal partnership agreement with the Canadian Iraqi-Turkmen Culture Association of London. Our study adopts a mixed-methods research approach by utilizing a cross-sectional socio-demographic survey of a sample of Iraqi refugees (quantitative analysis) and focus groups with selected Iraqi refugees in London, Ontario (qualitative analysis). Our results will provide a critical understanding of how refugees in Canada may disproportionately be affected by COVID-19 and what supports are needed.",2021,2022,Ryerson University,71596.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19663,202107UIP,Examining the Long-term Psychosocial and Health Consequences of COVID-19 on Children with Health Vulnerabilities and their Families,"The COVID-19 pandemic has imposed deleterious impacts affecting the quality of pediatric health care. For vulnerable children (e.g., those with various pre-existing health condition) and their families, person/family-centred care is essential to their health and well-being, particularly in times of systemic challenge which paradoxically has been taxed during the pandemic. Earlier research of this team has highlighted individual, family, health care provider and system wide strains during the pandemic. Building on that research, this study will examine the longer-term health and mental health impacts, with an integrally important examination of means of supporting children and their families. We will examine the need for shifts in care processes to diminish negative impacts and conversely optimize patient care. Using qualitative data collection, this study will illuminate the perspectives of children, their families, and health care providers about extended COVID-19 impacts on care delivery and experience. We will recruit pediatric patients with varying conditions, their parents and health care providers. Diversity in sex and gender as well as ethno-cultural and socio-economic backgrounds will be sought. Interviews, focus groups, review of care policies over the course of pandemic restrictions, and a Delphi consultation will be conducted. These multiple approaches will provide comprehensive information to guide pandemic preparedness and responsiveness, and as such, patient care. Recommendations for practice and policy will be offered.",2021,2022,University of Calgary,118492.89,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19664,202107UIP,Experiences of IPV and Housing Insecurity Among Young Women and Mothers During COVID-19: Mobilizing for Enhanced Service Delivery,"Stay-at-home orders that were put in place during the COVID-19 pandemic put some families at greater risk. For example, victims of family violence would find it difficult to access supports if the abuser was home all day and the increased stress of the pandemic could create tension that could make the violence worse. In fact, some have referred to this as the shadow pandemic and the pandemic paradox. This project will examine how family violence against women was impacted during this time, and how organizations that support these women adapted in order to continue to support their clients. Two studies are proposed. The first study will collect the most relevant information that already exists in the literature about how COVID-19 impacted family violence. It will synthesise this literature and identify important patterns such as who was most impacted and what supports were most useful. The second study will conduct interviews with young women and mothers who have experienced family violence. From these interviews we will extract patterns to identify the challenges and supports that they encountered when trying to seek help during the pandemic. In particular, we will identify patterns such as gaps in services that could increase homelessness and places where changes in service provision were helpful. This project will be a joint effort between researchers, community organizations, and women who have experienced family violence. By working together, we will learn from each other and help ensure that the information gained is useful to policymakers, advocates, and service providers. We have also integrated a number of strategies to help ensure a collaborative process that will lead to actionable recommendations to improve the lives of women that have experienced family violence.",2021,2022,University of Guelph,117024.28,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Women | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19665,202111WI3,Experiences of suicide-related thoughts and behaviours during the COVID-19 pandemic: A pan-Canadian qualitative study,"10 people die by suicide in Canada every day, and many more suffer from suicide-related thoughts and behaviours. The COVID-19 pandemic has disrupted the lives of all Canadians, and has been associated with worsening mental health and substance use, poorer access to health care, trauma, bereavement, financial stress, and social isolation. These tragic consequences are also risk factors for suicide. This study, the first of its kind, explores the stories of Canadians from four provinces who have had or our having suicide-related thoughts and behaviours during the pandemic through in-depth interviews. By hearing their voices and bearing witness to their stories, we can better understand how the pandemic has affected mental health, access to mental health care, and well being, and what factors can promote healing and recovery.",2021,2023,Centre for Addiction and Mental Health (Toronto),394977.09,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19666,202111WI2,Exploring the impact of COVID-19 on abortion care in Canada: A mixed-methods study dedicated to service delivery and utilization,"Evidence shows that the public health emergency restrictions imposed due to the COVID-19 pandemic have resulted in a decreased access to sexual and reproductive health services, in general, and abortion care, in particular. In Canada, the federal government reaffirmed at the outset of the pandemic that abortion care is an essential health service. As a result, a number of facilities around the country adopted new and innovative models of abortion service delivery, including telemedicine services and no-touch/no-test protocols, to reduce the risk of COVID-19 exposure while maintaining the availability of care. However, other facilities and clinicians were unable to provide continuous care. The economic and social disruptions caused by the pandemic also influenced pregnant people's decision-making and timely access to abortion services. Drawing from health services data, case studies with providers, and interviews with people who sought or obtained an abortion, our goal is to document the impact of COVID-19 on abortion care in Canada, identify innovations in service delivery, and explore how racism, colonialism, and linguistic hierarchies shaped access to care, reflected and/or perpetuated health disparities, and inspired resilience. In partnership with clinicians and advocates, this mixed-methods initiative aims to promote access to equitable and high-quality abortion services during the ongoing pandemic as well as help ensure the continued availability of abortion care in the face of future public health emergencies.",2021,2023,University of Ottawa,304940,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19667,202107UIP,"Exploring the Mental health and Addictions effects, Service impacts, and Care needs of children, youth, and families during the COVID-19 pandemic: The COVID-19 MASC study","The COVID-19 pandemic has drastically altered Canadians' daily lives and has had sweeping effects on mental health and/or addictions (MHA) care needs. With changes to the availability, delivery format, and accessibility of MHA services as a result of the pandemic, families of youth in need of MHA care may be experiencing considerable difficulties finding and connecting with appropriate supports. This project will explore the MHA needs of Ontario youth and families during the COVID-19 pandemic. A survey of 5000 Ontarians will be conducted in October, 2021. This survey is a third round of two prior surveys conducted in July, 2020, and February, 2021. The survey will identify and measure the MHA concerns, service needs and preferences, and experiences in the pandemic in relation to MHA concerns and demographics, for youth and caregivers. Survey findings from Round 3 will be explored in relation to findings from Rounds 1 and 2, to examine how youth and families' MHA needs and service preferences have evolved over the course of the pandemic. These findings will also be combined with an existing dataset of approximately 180 in-depth, one-on-one qualitative interviews, conducted with caregivers of youth with MHA concerns over the course of the pandemic. These interviews focused on caregivers' and their youth's MHA concerns, effects of the pandemic on their and their youth's MHA concerns, as well as their experiences of finding and accessing MHA care during the pandemic. This work will provide crucial information regarding the impacts of changes in access services to youth and families' existing MHA service preferences and needs. The findings will provide important information to design services and systems that transform MHA care across Ontario and Canada in response to the pandemic and in the future.",2021,2022,"Sunnybrook Research Institute (Toronto, Ontario)",115778.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19668,202111WI2,"Exploring the untold story of COVID-19: Understanding the wider and future impacts of the pandemic and finding solutions to improve population health, resiliency, and preparedness","The overall goal of this project is to describe the direct (for people who had COVID-19) and indirect (for everyone whether they had COVID-19 or not) impacts of the pandemic in southwestern Ontario for older adults with multimorbidity. We will pay special attention to social isolation. Southwestern Ontario has a population of approximately 1.6 million people and almost 50,000 COVID-19 cases. This part of the province represents the diversity of Ontario, in its people, environment, economy and health. We will conduct three studies to address the objectives of the CIHR Operating Grant call: ""Addressing the Wider Health Impact of COVID-19"". Study 1 will use questionnaires, interviews, and electronic medical records to describe the impacts of the pandemic including social isolation. Study 2 will use questionnaire data and electronic medical record data from people in southwestern Ontario to identify how the pandemic has affected different groups of people, especially those at higher risk because of their social and economic situations. In Study 3, we will use what we learned in Studies 1 and 2 to design a way of delivering family physician care called the COVID-19 Patient-Provider Exchange in Primary Care (COPE_PC) to help patients and their family physicians talk about the risk of social isolation on their health.",2021,2023,Western University,359641.97,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C19669,202005VR1,Expression and Purification of COVID19 Virus Spike (S) Protein for Diagnostics and Vaccines,"Projects described within this rapid response proposal relate to diagnostics and vaccine production. The reagents generated also have longer term ramifications for studying virus attachment and developing inhibitors that block host cell entry and virus mediated fusion. The work in this proposal focuses on the spike protein (S) of the coronavirus which mediates attachment and entry into the host cell and is the major target of neutralizing antibodies that block infections. The first goal of this proposal is to generate large quantities of the S protein is a mammalian expression system that can be easily scaled up for large scale production. The protein generated in this procedure can be used to produce immune diagnostic kits as well as serve as a component of subunit vaccines or booster shots directed against COVID-19. The second aim describes the generation of recombinant vesicular stomatitis (VSV) viruses that express the Spike (S) protein derived from COVID-19 virus. In the first experiments, VSV genome vector is modified to contain coronavirus S protein in place of its G glycoprotein which normally mediates attachment and entry of the host cell. The S protein changes the tropism of the recombinant virus and provides a new antigen target for the immune system. VSV is highly attenuated in human cells and is tightly controlled by the host antiviral interferon system. It is also the vaccine vector for the highly effective Ebola virus vaccine. The diagnostic and vaccine reagents developed in this proposal will be distributed and tested by colleagues at the Canadian Center of Vaccinology (Halifax) and VIDO-InterVac Vaccine Cenre in Saskatoon. The final aim of this proposal will use the reagents generated in the proposal to study cell receptors for COVID19 coronavirus and study infections in susceptible cells using model viruses of lower risk and pathogenicity.",2020,2021,Dalhousie University,103572.75,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C19670,202107UIP,FOCUS on Adolescents: A mixed-methods study to optimize COVID-19 recovery and renewal efforts among adolescents in Canada and France,"The COVID-19 pandemic and corresponding health, social and economic implications have presented the potential for the health and social well-being of adolescents ages 15-19. For example, experiences of school closures and other public venues have had significant effects on adolescents - an age group whose need for social engagement and connection is developmentally rooted and exacerbated. As we move into the recovery and renewal phases of the COVID-19 pandemic, ongoing social, economic, and cultural changes are likely to impact the health and social trajectories of adolescents, underscoring the urgency for health, social and economic systems to keep pace with these changes. Our aim is to provide time-sensitive understandings about adolescent health and social well-being during and following the next phases of the COVID-19 pandemic. Specifically, we plan to strike a FOCUS on Adolescents Youth Advisory Committee (YAC) to co-lead adaptations to our existing FOCUS research infrastructure in Canada and France that currently only has the capacity to focus on young adults (i.e., those over the age of majority). Alongside the YAC, we will identify strategies to identify the adaptations that need to occur within our broader program of FOCUS research, including age-based and country-specific adaptations to involve adolescents ages 15-19 in a series of annual interviews (n=20 per country) and biannual cross-sectional national online surveys (n=3,500 per country per wave, including ~1,000 between the ages 15-19). Towards the end of our study, using a community-based approach to mixed-methods synthesis, we will also host one Participatory Planning Summit in both Canada and France with knowledge users (e.g., clinicians, decision-makers) and other stakeholders (e.g., YAC members, adolescent youth organizations) to identify strategies to improve adolescent health as we move into the next phases of the COVID-19 pandemic.",2021,2022,University of British Columbia,88847.35,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Europe,,,,Canada,Canada | France,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Other secondary impacts,2021 +C19671,202107UIP,Follow CONCEPTION Study and Mitigate Pandemic Effects on Families,"The COVID19 doubled the prevalence of women presenting with mental health symptoms during pregnancy and the postpartum period. The demonstrated increases in prenatal maternal depression during the COVID19 pandemic is alarming since maternal stress, anxiety and depression during pregnancy have been associated with several deleterious psychological and health-related consequences on mothers and their babies. These include neonatal events, postnatal mental health, mother'-infants psychological well-being and attachment, children's neurological, neuropsychological and psychological outcomes. This research project will follow up with the 2468 Canadian women participating in the CONCEPTION Study and their children until 18 months to extract information on families who might need services in the coming months and years. We will investigate maternal symptoms trajectories as well as infants' behavioral and cognitive outcomes. Importantly, we will partner with several networks and agencies across Canada to provide navigation tools for those searching for services. This research project will be directly beneficial to Canadians by estimating the consequences of the pandemic on infants' neurodevelopment nationally (current N=2468 Canadian women). It will provide the valued information of how many and to which extent care providers need to be prepared to offer timely services. It will bring forth additional and timely care solutions for families across Canada.",2021,2022,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",118500,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19672,202109EG2,Forgotten at sea: occupational health challenges for seafarers during the COVID-19 pandemic,"The COVID-19 outbreak has resulted in unprecedented challenges to occupational health and safety for essential workers. Essential workers need legal protection, accurate information, and supportive working environments. Drawing upon a group of essential, as well as marginalized workers at sea, seafarers, this research will examine the health challenges they are facing during the pandemic, and explore solutions to address the inequalities faced by them. This research aims to explore the occupational health and safety challenges faced by Canadian and international seafarers during the COVID -19 outbreak, to understand the impact of public health measures on their health and well-being. It also attempts to identify the regulatory barriers and conflicts negatively affecting seafarers' health and safety that existed in international maritime, health, and labour regulations, and to explore possible policy and management interventions to improve seafarers' mental and physical well-being in the new normal of the pandemic. The specific research questions are as follows: (1)What are the impacts of COVID-19 on the health and well-being of maritime workers (Research Area#2)? (2)Are there any regulatory gaps/systematic discrimination that exists in public health law and policies, which make seafarers face structural inequalities during the pandemic (Research Area #1)? (3)What solutions can be developed at the regulatory level, management level, and community level to empower seafarers? This research will adopt a mixed-method approach, including legal doctrinal analysis, quantitative survey, and qualitative interviews to answer the above research questions. We hope to identify (1) the prevalence of psychosocial distress among seafarers during the pandemic, (2) the limitations of the current legal framework in protecting seafarers' occupational health, and (3) the gaps that existed in the maritime and public health governance system.",2021,2022,Memorial University of Newfoundland,112864.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19673,202107UIP,Forgotten Youth and Photovoice: Using Visual Methodology to Give Voice to Muslim Siblings of Children with Disabilities,"The COVID-19 pandemic-induced economic and mental health crisis has disproportionately affected ethnic and racial minority families of children with disabilities, especially newcomers to Canada. For Muslim communities, the pandemic is exacerbating pre-existing systemic inequities due to racial discrimination. Parents struggled to cope with post-migration stressors without access to a full range of resettlement services. Consequently, they relied on their young son and/or daughter with no medical conditions to share caregiving responsibilities for their disabled siblings. Multiple COVID-induced stressors, including losing social interaction with friends/peers, prolonged home confinement, and learning to navigate virtual schooling in a new country, had adverse mental health on Muslim immigrant youth siblings of children with disabilities. Caregiving and translating the public health guidelines and directives that are important in reducing the risk of the virus for their limited English proficient parents put an additional burden on the siblings. In partnership with the project's Principal Knowledge User (PKU), Dr. Mohammed Baobaid, the proposed community-engaged and arts-informed research will explore the lived experiences of Muslim immigrant youth siblings of children with disabilities during the COVID-19 pandemic from their perspectives. As part of a Knowledge Translation process, we will use artistic tools developed during the research process (e.g., participant-generated photographs) to disseminate research-generated knowledge beyond the academy to health care and other service providers, service users, health practitioners, and policymakers. Study results will inform effective sex and gender-sensitive policy, practice, and clinical guidelines.",2021,2022,King's University College - Western University,118275.64,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19674,202111WI2,"From languishing to flourishing: Exploring the wider and longitudinal impacts of COVID-19, use of supports, and recovery for families","BACKGROUND: High-quality, contemporary data on coping and recovery for families during an unprecedented pandemic that is far from over is crucial to inform further immediate and long-term action as variants circulate amidst public reactions to existing measures. COVID-19 supports were implemented quickly and the wider impact of the well-being of families are largely unknown. Examining languishing and flourishing outcomes is imperative for mitigating the longer-term impacts of the COVID-19 pandemic. Also, understanding the effectiveness of rapidly implemented government supports to support flourishing outcomes in mothers, youth and families is important to inform the need for additional supports and resource allocation moving forward. METHODS: The All Our Families (AOF) study is a pregnancy cohort in Calgary that started in 2008 and has followed families over time and will have surveyed mothers and youth at four time points during COVID-19. The primary aim of this mixed methods study is to continue engaging with mothers, youth, and families through the AOF cohort to understand the languishing and flourishing impacts of the ongoing COVID-19 pandemic. To supplement previous AOF findings and gain a deeper understanding of how these impacts have been ameliorated through participation in effective interventions and supports, qualitative research will be undertaken in the form of focus group discussions with mothers, youth, and community stakeholders. A recovery survey for mothers and youth will also take place, focused on studying how to bolster post-traumatic growth following stressful life events. IMPORTANCE: We are poised to rigorously examine and compare the changing nature of social, economic, and health-related impacts associated with COVID-19 over time to provide contemporary evidence to decision makers to assist in the planning of future pandemic waves and long-term recovery.",2021,2023,University of Calgary,317184.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts | Economic impacts,2021 +C19675,202109PTT,Functional analyses of pathogenicity determinants of SARS-Coronavirus-2 delta variant,"Coronavirus disease-19 (Covid-19) pandemic is the biggest global health crisis in recent history, resulting in over 4.5 million deaths worldwide. Covid-19 is caused by SARS-Coronavirus-2, a novel coronavirus that was unknown until human infections were first reported from China in late 2019. The virus has spread to nearly all communities across the globe, leading to hospitalizations and deaths. Highly transmissible virus variants are now regularly emerging and spreading among populations in several countries exacerbating the current crisis. To date, there are no effective antivirals to combat the disease and the evolution of new virus variants is threatening the efficacy of available vaccines. The emergence of highly infectious virus variants was accompanied by genetic changes of viral proteins, which have roles in virus entry, neutralizing host antiviral defenses and exploiting cellular pathways during infection. Several new genes were also discovered recently in SARS-Coronavirus-2 genome which may have roles in virus fitness and pathogenesis. We have been exploring the interactions between SARS- Coronavirus-2 and the host cells over the last year and have identified multiple cellular pathways playing critical functions during infection. With the present study, we aim to investigate how mutations in SARS-Coronavirus-2 genome led to emergence of highly virulent and fast spreading delta variant. Understanding the mechanisms behind increased virulence of delta variant is critical, for effective disease management, development of vaccines and therapeutics and to rapidly respond to the emergence of new variants in future. We will also explore the roles of proteins encoded by novel genes in infection and virus spread, to better understand the biology of SARS-Coronavirus-2. During this study, we will examine several previously unexplored aspects of the virus biology and identify novel targets for development of effective antivirals.",2021,2024,University of Saskatchewan,237000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +C19676,202002OV4,Genomic epidemiology and evolutionary dynamics of COVID-19 and other emerging corona viruses,"Emergence of the 2019 coronavirus (SARS-CoV-2) has highlighted the severe impact emerging zoonotic pathogens have on human health, the global economy, and health service delivery. Phylogenetic analyses of SARS-CoV-2 genomic sequences improve our understanding of host reservoir species, assess the potential for transmission to humans, and illuminate evolutionary dynamics relative to other viruses in Coronaviridae, informing response to current and future epidemics. We will study the genomic evolution of SARS-CoV-2 to investigate if particular motifs are under selection for increased virulence and immune evasion. We will compare SARS-CoV-2 with genomes of other zoonotic coronaviruses to elucidate common genomic features associated with virulence, host switching, and human-to-human transmission. We will also evaluate spatiotemporal transmission patterns of SARS-CoV-2 across different populations using Bayesian phylogeographic analyses. Such analyses allow identification of spatially and temporally structured, clinical and epidemiological parameters such as the basic reproduction number, period of infectiousness, and true viral prevalence over time within different populations. We will also elucidate the reservoir host species of SARS-CoV-2 in concert with collaborators from the Chinese Centre for Disease Control as well as other Canadian researchers by probing unique environmental samples as well as both novel and existing datasets available for coronaviruses. Phylogenetic co-speciation analysis will explore whether coronaviruses are more likely to jump between phylogenetically proximate host species allowing development of a predictive framework to anticipate future zoonotic events. We will identify genomic factors of SARS-CoV-2 associated with virulence, estimate vital epidemiological parameters, and illuminate potential reservoir species. With the Chinese CDC, we will help focus the response, control and elimination of the current, and future, coronavirus outbreaks.",2020,2022,University of British Columbia,236250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Canada | China,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Disease transmission dynamics",2020 +C19677,202005VR5,"Gig couriers delivering people, food and packages in a pandemic: Containment strategies to mitigate the occupational and public health impact","Gig courier workers, such as Uber Eats, Amazon Flex, and Lyft drivers, have been busier than ever during the Canadian COVID-19 pandemic as the public attempts to avoid illness by ordering take-away food, shopping online and taking ride-hails rather than public transportation. This places gig courier workers in a unique position to become infected with COVID-19 and transmit it to others as they move people, food and packages from one location to another. Although gig couriers are key vectors between where people live (e.g. homes, care facilities) and the outside world, formal strategies do not exist to protect them from exposure and to mitigate their role in disease transmission. Importantly, this risk is not expected to change anytime soon as the high use of couriers will likely not decline as the economy re-opens. This study will contribute to coronavirus containment strategies by identifying disease transmission risks embedded in gig work contexts and practices, developing clear and tailored interventions for gig courier workers about gig courier disease-related safety and transmission, and widely disseminating results, in live time, as they are identified. Using framework analysis explicitly geared towards generating policy- and practice-orientated findings within limited time periods, we will: document existing courier safety organisational policy; map gig courier worker work, disease exposure and transmission conditions (with attention to gendered dimensions) via social media forums and in-depth interviews with workers and courier firm representatives; and categorise disease transmission risks. Supported by our Strategic Advisory Committee of unions, government municipalities, employers, and vulnerable worker advocates, and using real-time public health communications, this study will create effective national interventions to reduce gig courier disease exposure and protect the public health of Canadians using these courier services.",2020,2021,University of Waterloo,122046,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +C19678,202111WI4,Gigii-bapiimin: Exploring Resilience and The Impacts of COVID-19 on the Health and Wellbeing of Indigenous People Living with HIV/AIDS in Manitoba and Saskatchewan,"Very little is currently known about the impacts of COVID-19 on the physical, sexual, spiritual and mental health of Indigenous people living with HIV/AIDS (IPHA) in Manitoba and Saskatchewan. We propose a community-based participatory action research study grounded in an Indigenized ethical space and utilizing etuaptmumk (Two-eyed Seeing) to interweave Indigenous and Western ways of knowing, being, doing and systems approaches to respond to knowledge gaps about the impacts of the COVID-19 pandemic on the health and wellbeing of IPHA in Manitoba and Saskatchewan. We will explore the indirect/wider impacts of the pandemic on the health of IPHA in both provinces (including their access to health and community-based services, ceremony, and land-based activities), and ways to mitigate the impacts of COVID-19 on IPHA. Our project will strengthen capacity among IPHA and Indigenous-led organizations that serve IPHA. The study is guided by an Elder and Community Guiding Circle made of IPHA from Manitoba and Saskatchewan, Knowledge Holders, as well as being culturally grounded within Indigenous philosophies, and ceremony-related elements, including the use of sweat lodges, smudging, pipe ceremony, oral tradition, sharing circles, and land-based healing activities. We will use an Indigenous wholistic theory, storywork methodology and a decolonizing participatory action research approach. We will conduct 14 sharing circles (five IPHA per circle; n=70) and individual interviews with IPHA (n=30) across Manitoba and Saskatchewan to gather stories. We will also interview healthcare/service providers (n=30) and community advocates/leaders (n=20) that work with IPHA. This project will inform services, campaigns and significantly contribute to pandemic research, policy response, and generate recommendations for change to health and social systems. It will also inform pandemic intervention preparedness among Indigenous people in Manitoba and Saskatchewan.",2021,2023,University of Manitoba,311993.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Other,Health Personnel | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19679,202111WI2,Healing the Healers: Using experience-based co-design approach to address occupational burnout among health care workers in long-term care,"Before COVID-19, burnout was common among health care workers (HCWs), but now, up to 70% of HCWs are at increased risk of burnout and mental health concerns. HCWs especially those in long-term care (LTC) homes are facing greater risk of burnout and many (up to 64%) reported feeling emotionally exhausted and are unable to give proper care to residents because of heavy workload, staff shortages and stress of witnessing high (82% COVID-related) deaths among residents. Because of this, some HCWs have left their jobs which places even more pressure on the remaining staff, causing even greater burnout. As stress levels among HCWs continue to rise, supporting the personal health and well-being of those working in LTC is urgent if we are to improve the quality of life of residents and caregivers. During these difficult times, we need solutions that reduce, if not get rid of, the risk of burnout among HCWs. For this project, our goal is to reduce burnout among HCWs in LTC and improve workers' health and well-being by creating together (co-design) with HCWs potential solutions/interventions and programs that they view to be most effective. We will host a series of meetings and activities with a team of HCWs (e.g., PSWs, nurses, managers) from Ontario LTC homes, to share ideas and get a good understanding of their work experiences, the LTC home during COVID, and resident care. Together, we will identify the top key issues that put workers at greater risk of burnout and design healthy workplace strategies and policies to reduce stress and burnout. This joint effort to create a workplace wellness program with HCWs will ensure that the most effective and appropriate supports are in place to help workers in LTC. Results from our study not only will benefit the selected LTC homes but can also, be applied in other LTC homes across Canada. Ultimately, the knowledge we gain will be used to create wider public and mental health services for HCWs in LTC and other health settings.",2021,2023,McMaster University,179472.99,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C19680,202111WI3,"Health equity during the pandemic recovery period: updated knowlege syntheses, policy tracking and health outcome monitoring","Health equity, or fairness in health outcomes, was prominently mentioned during the pandemic. Racialized people, women, people with a low income, people experiencing homelessness, people who use substances and people who are incarcerated were disproportionately affected during the pandemic. Disparities in who was getting and being killed by Covid-19, and who was getting vaccinated were widely reported in national media and in national reports such as from the Public Health Agency of Canada. There was also some attention to the disproportionate effect of pandemic related restrictions on people experiencing disadvantages. Interventions and policy changes that can address the inequities exposed during the pandemic have been well studied and described. These policy changes include changes to governmental income supports (ex. a basic income, paid sick leave), housing policies (eviction prevention, permanent supportive housing), supports for victims of intimate partner violence, supports for children (e.g. access to childcare, healthy food distribution), access to preventative health care (e.g. HIV screening), and comprehensive changes to address racism. We will attempt to translate the recent attention to inequities into lasting improvements including policy changes and clinical practice changes. Our three objectives are to: (1) support the implementation of policy and practice changes that promote health equity by maintaining up-to-date knowledge syntheses (including recommendations) for interventions that can promote health equity, (2) monitor the implementation of policy and practice changes aimed at promoting health equity, (3) measure disparities in actual health outcomes that are sentinel indicators for the effects of the policy and clinical practice changes identified. We will exchange knowledge with decision makers and other stakeholders.",2021,2023,Unity Health Toronto,145465.86,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19681,202111WI2,Healthcare Governance for a Post-COVID Canada: Leveraging Hard-Earned Experience for a More Equitable and Supportive System,"The COVID-19 pandemic has served as a deadly reminder of the critical importance of public health (including immunization). Despite the International Health Regulations 2005, the epidemiological warnings, and post-SARS recommendations, Canada was ill-equipped to anticipate the pandemic, ill-prepared to effectively meet its demands, and it relied on provincial interventions, which were driven in part by political objectives. The result was unnecessary deaths, service breakdowns, and healthcare worker (HCW) burnout. All of this clearly points to a pressing need for more robust governance standards, institutions, and practices organized by a more coherent and resilient governance framework instantiated in a comprehensive Canadian Public Health Act. Through its diverse and pan-Canadian team, the 'Healthcare Governance for a Post-COVID Canada' (HGPC) Project will examine the impacts of COVID-19 of public health. Evidence generated will inform a governance framework design through a process that draws on the experiences of groups profoundly impacted by the pandemic but habitually sidelined in the development of rules and standards. Specifically, it will draw on data from regulated and unregulated HCWs and support personnel, and from individuals from equity-seeking groups (including Indigenous and other racialized individuals and newcomers). Evidence generated will feed into a series of deliberative engagement exercises wherein a selection of policymakers and knowledge-users and ground-level actors will collaboratively consider a range of scenarios and collectively imagine the future that Canada's public health governance framework needs to deliver. We will then make recommendations for a public health governance framework, with legislative elements.",2021,2023,Dalhousie University,386757.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Policy research and interventions,2021 +C19682,202002OV3,Host cellular protein substrates of SARS-CoV-2 proteases,"The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to COVID-19 disease in China and worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Currently, the pathogenic mechanisms that lead to COVID-19 and related SARS/MERS-CoV diseases are not understood. In this study, we will identify the host proteins that are targeted by a viral protein called a protease using an unbiased proteomics approach. Identifying the protein targets of SARS/MERS-CoV proteases will reveal into the protein sequence that binds to the proteases. We will engineer and optimize decoy protein sequences that will effectively block SARS/MERS-CoV protease function and thus, inhibit SARS/MERS-CoV infection. Uncovering the proteins that are targeted by the SARS/MERS-CoV proteases will also provide a catalog of the host processes that these viruses affect, thus gaining insights into the pathogenic mechanisms that lead to COVID-19 disease.",2020,2022,University of British Columbia,248409,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +C19683,202002OV2,Host Response Mediators in Coronavirus (COVID-19) Infection,"The coronavirus (COVID-19) epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. WHO and others are launching clinical trials of novel anti-virals. We have a unique opportunity to complement trials of anti-virals with investigation of modulation of the human host response to improve outcomes of COVID-19. We are proposing to ""repurpose"" a class of drugs (ARBs) for hypertension (high blood pressure) that have been shown to prevent lung injury in influenza and could work on corona because influenza and coronavirus bind to the same cell receptor in the lung. ARBs are commonly prescribed for high blood pressure (50-70% of patients). To date, there have been no clinical studies of ARBs in COVID-19. We call our study ARBs CORONA. We believe that ARBs can decrease the severity of COVID-19 and mortality of hospitalized COVID-19 infected adults. We will evaluate safety and effectiveness of available ARBs in COVID-19 in a multicentre study of 497 hospitalized adult patients who are or are not already on ARBs. Key personnel are in place to expedite this study. If this study is successful, ARBs can potentially limit complications and mortality of COVID-19. Potential results: ARBs are inexpensive clinically available cardiovascular drugs. If this study is successful, ARBs can potentially be used globally to limit complications and death due to COVID-19.",2020,2021,University of British Columbia,191977.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C19684,202005VR5,Household Transmission Dynamics and Vial Load among Asymptomatic SARS-CoV-2 Infected Children,"Children have milder disease than adults and many have no symptoms even when infected by SARS-CoV-2. At present, we do not know how likely asymptomatic-infected children are to transmit the infection. Gaining an understanding of this issue is crucial to determining the role children play in transmission and what the risks will be to other children and adults when children return to school. To answer these questions we will enroll children who are brought for care due to non-infectious reasons (e.g. fall, cut, injury, pain) to 20 emergency departments across Canada and the United States. These sites are participating in the CIHR-funded, 57-site, Pediatric Emergency Research Network (PERN)-COVID-19 study, and currently perform screening of select asymptomatic children for SARS-CoV-2. Participating sites will enroll 400 asymptomatic SARS-CoV-2 positive children and 1,200 uninfected children (3:1 ratio of uninfected to infected child). Study aims: 1) Household Transmission Dynamics: Data will be collected regarding exposures and symptoms at baseline and again at 14 days for enrolled children (infected and uninfected) and their household members. Household members who develop symptoms of COVID-19 will be encouraged to have SARS-CoV-2 testing done (if not already) and the results will be obtained. Analyzing and modeling this information, comparing households with transmission versus those without, will help us understand the transmission risk posed by asymptomatic SARS-CoV-2 infected children. In particular this information will inform social distancing policies (e.g. school re-opening) 2) Viral Load Quantification: All SARS-CoV-2 positive specimens will have viral load quantification performed. These results will be analyzed alongside those from aim #1 to determine the relationship with household transmission. Viral load quantification data will also be analyzed alongside symptom evolution data to inform our understanding of the presymptomatic state.",2020,2021,University of Calgary,375053.25,Human Populations,Unspecified,Children (1 year to 12 years) | Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease transmission dynamics",2020 +C19685,202111WI2,How do perceptions of Covid-19 risk influence health decisions in pregnancy? A mixed methods study,"Pregnant people have experienced many difficult circumstances during the Covid-19 pandemic, which likely affected the way they made and enacted health decisions. We know that pregnant people have a higher risk of severe Covid-19 disease than non-pregnant people, resulting in higher rates of hospitalization and death. Additionally, the well-being of women has been affected by policies designed to prevent and control Covid-19 infection, which have resulted in higher rates of intimate partner violence, mental health distress, employment loss and increased childcare responsibilities. This research seeks to understand how these circumstances have changed the health decisions of pregnant people. Health decisions during pregnancy are particularly important because they have longitudinal effects on the health of the child and family. We will use administrative health data from Ontario and BC to examine how vaccination, prenatal care and place of birth, and mental health have changed between people pregnant before and during the pandemic. We will conduct qualitative interviews with people pregnant during the pandemic to understand why and how their perceptions of Covid-19 risk influenced their health decisions. For example, how did they balance need for social connection and support with Covid-19 risk precautions about physical distancing and limiting contacts outside the household? By combining these two types of data together, we will be able to describe changes and offer explanations for those changes. This new knowledge will help inform public health policy and clinical counselling decisions as the Covid-19 pandemic continues and in the future.",2021,2023,McMaster University,301499.55,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2021 +C19686,202107UIP,How is COVID-19 continuing to impact children with and without Attention-Deficit/Hyperactivity Disorder?,"This study examines how COVID-19 is continuing to impact children with and without Attention-Deficit/Hyperactivity Disorder (ADHD). In Spring 2021, our research team conducted a cross-Canada survey examining the experiences of children and parents with and without ADHD. Parents completed online questionnaires assessing COVID-19 stress, parent and child mental health outcomes and lifestyle factors, parental beliefs regarding parenting, the parent-child relationship, and parent beliefs and behaviours related to child learning. The proposed study aims to follow up with these families to understand their experiences in the next school year and determine how prior levels of pandemic-related stress predict later child and parent outcomes. This study uses a one-year longitudinal design to follow up with families from our existing data collection (Time 1) at two additional timepoints (Time 2 and Time 3) in the upcoming school year. This study has three main objectives: (1) To examine how children with and without ADHD and their parents are faring in the aftermath of the pandemic, and (2) To examine how prior COVID-19 stress predicts later parent and child outcomes for children with and without ADHD, and (3) To provide meaningful information about malleable targets for the management and treatment of ADHD in the wake of the pandemic. Five hundred and thirty-nine parents in the ADHD group and 131 parents in the non-ADHD group of our original study have agreed to be contacted for future research. A timely response to support families with and without ADHD is only possible with an understanding of the continued and long-term effects of COVID-19 on child mental health and important lifestyle factors, parent mental health, and child learning-related parental beliefs and behaviours. Knowledge from this study will lead to targeted evidence-based resources for children and families to support them in recovering from the pandemic.",2021,2022,Saint Paul University,118411.52,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other | Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19687,202111WI3,How the COVID 19 pandemic and overdose epidemics are changing addictions medicine: stakeholder perspectives,"People who use drugs have felt the impacts of the COVID 19 pandemic with on their access to addictions medicine at time when access is crucial. The opioid overdose crisis has resulted in an estimated 21,174 deaths in Canada between 01/2016 and 12/ 2020.1 Fentanyl has overtaken the unregulated street supply of drugs making it hard to avoid, has led to more frequent injection and increased the risk of overdose due to the variable potency. Fentanyl use is also leading to ever-increasing drug tolerance creating challenges for people who use fentanyl (PWUF) and their treatment providers. With this changing context has come an evidence gap addictions clinicians must navigate as they change(d) their practices to improve care and access during the pandemic. Some changes are perceived by stakeholders to be long overdue while others as time-limited to the pandemic. Our proposed exploratory qualitative research project aims to examine how fentanyl has changed addictions medicine in general and in the context of the COVID-19 pandemic, and how clinical (e.g., physicians and nurse practitioners) and PWUF stakeholders (i.e., people receiving opioid agonist treatment; safer supply; not in treatment; on a waitlist for treatment) understand the impact and sustainability of these changes. We will interview 90 people including physicians who prescribe methadone/suboxone and safer supply as well as people enrolled methadone/suboxone/safe supply and people who are not in treatment to understand the impact of fentanyl tolerance on addictions medicine. We will used thematic analyses to understand our data, consult with our advisory group, clinicians and people who use drugs to interpret our data. Our multi-disciplinary team includes clinicians, people who use drugs, junior and senior academics, and experts in knowledge translation. Our findings will be used to add to the evidence base about if and how to revise treatment regimens and for advocacy purposes.",2021,2023,University of Toronto,254332.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19688,202109ER5,How will the immune response to COVID-19 vaccination among Indigenous peoples in the Northwest Territories change over time?,"Immune response to vaccination can be different for many people, depending on age, sex, gender, and ethnicity. Some may have a reduced response, and it is important to measure this among different populations to understand the effectiveness of the COVID-19 (C19) vaccine. This is essential for pandemic policy and planning to implement strong vaccination programs, ease the impact of C19, and find out if and when booster shots may be needed. With full engagement in research leadership, collaboration, and decision-making, and sharing of knowledge with the communities, the Community Advisory Board (CAB) and partners this project will: 1) look at C19 immune response at two time points using dried blood spots taken by a finger prick among both vaccinated and unvaccinated Indigenous peoples in 4 Northwest Territories (NT) Tlicho communities; and 2) share results with communities and all partners. We will collect important new information for the prevention of C19 as there is currently limited evidence available on the effectiveness of the C19 vaccine for Indigenous peoples. This work has involved a process of consultation and agreement with the Tlicho Government to ensure methods are culturally safe and relevant and that outcomes will provide direct community benefit. We will provide training and employment to local community staff, as we have done successfully in other projects. The team is ready to partner with the communities and the CAB to collect this evidence quickly by expanding an ongoing C-19 project, which is working with the same 4 communities. The project is co-led by Rachel Oystrek, an experienced Indigenous Public Health Program Coordinator, and Hotii ts'eeda NT SPOR Support Unit with support from Dr. John B. Zoe, a highly respected Indigenous leader. The team includes academic and local researchers, public health policymakers, and international and national collaborators. Collecting this information is necessary for the future prevention of C19 in NT.",2021,2022,University of Alberta,393349.69,Human Populations,Other,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C19689,202002OV2,Identification of biomarkers that predict severity of COVID-19 patients,"The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are over whelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.",2020,2022,Dalhousie University,750000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | Europe | Western Pacific,,,,Canada,China | Viet Nam | Spain | Italy | Mozambique | Sudan | Ethiopia | Egypt | Morocco | Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C19690,202112FO1,Identifying and addressing barriers to cross-sectoral and community-based wastewater surveillance for the mitigation of secondary infections in rural and remote First Nations,"The proposed project tracks SARS-COV2 in wastewater in First Nations in Alberta and Northwest Territories through a community-engaged approaches. The research team has effectively deployed methods within urban settings, as well as in larger First Nations in Alberta. This experience will be leveraged to address barriers in small rural and remote First Nations, utilizing community-based Indigenous-led approaches. Through implementation of wastewater-based epidemiology (WBE) of SARS-COV-2 with rural/remote Alberta First Nations, contextualize and address barriers to wastewater surveillance in support of effective public health responses. The project builds on the lessons learned that point to barriers to existing wastewater surveillance programs that limit the full and meaningful participation of First Nations. Through a transdisciplinary approach, we will address: (1) the infrastructure-related barriers to meaningful wastewater surveillance programs, (2) community-led approaches to meaningful participation in the tracking of SARS-COV2, (3) collaborative and co-created response strategies to mitigate disease spread, and (4) Indigenous-centered knowledge mobilization strategies. Through a research project that spans engineering, science and medicine, and the full participation of Indigenous Knowledge Keepers, health practitioners and community members, the research will inform community vulnerability and barriers to participation. Through a collaborative approach, building on existing relationships with First Nations, the research team brings together experts in wastewater-based surveillance, models of care, community infrastructure and Indigenous knowledge. The team brings together extensive experience working with Indigenous peoples, with research underpinned by OCAP(r) and aligned in Indigenous-led methodologies.",2021,2022,University of Calgary,197500,Human Populations | Viruses | Environment,Unspecified,Adults (18 and older),Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Environmental stability of pathogen | Disease transmission dynamics | Community engagement,2021 +C19691,202111WI2,Identifying and contextualizing best practices in responding to violence against women during the COVID-19 pandemic: a mixed-methods study of the experiences of staff and survivors in three Canadian provinces,"Violence against women (VAW), including domestic violence and sexual violence, has increased during the COVID-19 pandemic with detrimental impacts on women's health. VAW organizations across the country quickly adapted to meet these conditions. However, what is unclear is how VAW interventions were implemented, what factors internal and external to VAW organizations impacted these processes, and the outcomes for VAW survivors. This is a barrier to identifying which VAW response strategies worked best and the contextual factors that facilitated success, critical to ameliorating the impacts of COVID-19 on VAW and preparing for future emergencies. This research aims to address these gaps by building upon our previous rapid research on the processes and experiences of adapting VAW services in Toronto. As a diverse team of academics, VAW organizations, and women with lived experience of violence, we will mobilize our existing networks and extend this research across the provinces of Ontario, Nova Scotia, and New Brunswick. Our research will include a survey of VAW staff and in-depth interviews with staff and survivors who have accessed VAW services during the pandemic to develop an up-to-date understanding of how VAW services were adapted during the pandemic, the contextual factors (like funding, staff wellbeing, and collaboration with other sectors) that impacted these adaptations, and how well services have been meeting the needs of VAW survivors, including how these needs have been impacted by COVID-19. In line with our earlier study in Toronto, we will investigate the experiences of VAW survivors facing different forms of marginalization (e.g., racialized women or women experiencing economic instability, who use drugs, or who identify as sexual or gender minorities). This research will further examine how provincial and municipal policies and practices have served as barriers or facilitators and the experiences of VAW survivors in rural and remote areas.",2021,2023,Dalhousie University,394721.13,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Drug users | Sexual and gender minorities | Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19692,202107UIP,Identifying and responding to children and youth mental health need during the COVID-19 pandemic: Examination of individual and agency level factors impacting outcomes in Ontario,"Although children and youth are less likely to be hospitalized by COVID-19, they remain vulnerable to the psychological impacts of the pandemic. Abrupt changes to daily routines of children, various pandemic-related parental stressors, social isolation from friends and extended family members and lack of access to social and structural supports during this time might leave children vulnerable to psychopathology, and parents with fewer resources to meet their children's needs. Yet, an alarming number of these children and youth did not have their needs adequately met prior to the pandemic. The current study utilizes interRAI data from over 50 participating agencies across Ontario, including over 36,000 child and youth assessments. Researchers will examine the trends and characteristics of children and youth prior to and during the multiple waves of the pandemic, as well as study the impact of services and associated risk factors (e.g., staff shortages, program closures) on changes in mental health and child/youth-level outcomes during the COVID-19 pandemic, compared to pre-pandemic data. Moreover, child and agency level data will be examined to evaluate mental health outcomes based on sex, gender, and area-based social-economic status, to indicate populations with the greatest mental health decline (i.e. depression, anxiety, behaviour, self-harm) and poorest quality of life indicators (e.g., health, education, relationships). Family and social supports will be evaluated alongside these risks, by determining protective effects such as caregiver involvement, financial assistance, and interpersonal resources. Researchers will engage in knowledge exchange with health system partners, policy makers and national researchers to create a network to share findings that are broadly accessible to health system administrators across the country.",2021,2022,Western University,118413.89,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19693,202111WI4,Identifying effective interventions for addressing social issues and disparities faced by Indigenous individuals with substance use problems in response to the COVID-19 pandemic,"In the context of ongoing settler-colonialism and systemic racism, Indigenous Peoples have elevated risk for health and socioeconomic consequences from pandemics. A clear priority concern is the pandemic's impact on those who have or are at risk of developing substance use problems. In addition, the needs of youth are a priority among Indigenous Nations. Many Indigenous families within Canada are experiencing enormous stress, while also experiencing greater disconnection from community supports and resources. Likewise, organizations serving Indigenous youth are struggling to understand the most important needs and resources of the communities and families they serve. This project, in collaboration with an Indigenous-serving substance use treatment organization and a First Nations school, seeks to understand the most important needs of potential interventions among First Nations and Inuit families in eastern Canada. With knowledge obtained from this research, these partners will be able to identify potential interventions to best meet the needs of the youth and families they serve--particularly for supporting youth who have or at risk for developing substance use problems. We also expect to understand key concerns concerning service utilization in the context of ongoing settler-colonialism (including recent events such as the identification of children buried at former residential schools). A strength of the proposal is that it is rooted in local initiatives-thus maximizing relevance of findings-but also includes data collection with multiple diverse First Nations/Inuit communities-thus increasing the relevance of findings across Indigenous communities across Canada.",2021,2023,McGill University,274078.65,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19694,202109EG5,Immunogenicity and durability of COVD-19 vaccines in persons living with human immunodeficiency virus,"Despite the effectiveness of antiretroviral drug treatment, persons living with HIV (PLWH) can have weakened immune systems that respond poorly to vaccination, compared to the general population. Little is known about how PLWH respond to the novel mRNA or viral vector-based vaccines developed against COVID-19 . As they may be more prone to develop severe infection, it is important to determine how well the vaccines work and how long vaccine-induced immunity lasts in PLWH. If there is a weaker response to the vaccines in PLWH, this would indicate that additional doses and more frequent boosting may be required to provide adequate protection. We will study the responses of approximately 200 PLWH who received matched or unmatched COVID-19 vaccines to find out what factors related to HIV infection affect responsiveness to the vaccination and the need for additional vaccine doses.",2021,2022,Memorial University of Newfoundland,226572,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C19695,202107UIP,Impact of COVID-19 and related stressors on children's weight and mental health outcomes,"The COVID-19 pandemic has disrupted the economic stability and daily routines of Canadian families. However, little is known about the long-term impact of these disruptions on children's health outcomes. The goal of the proposed study is to examine how the COVID-19 pandemic has impacted the weight and mental health outcomes of Canadian children. To achieve this goal, we will use data from 300 children aged 18 months to 5 years who are participants in the Guelph Family Health Study. The Guelph Family Health Study is a well characterized family-based intervention study that collected family-level data prior to and during the COVID-19 pandemic. Thus, the Guelph Family Health Study is ideally suited to identify how stressors due to COVID-19 restrictions are associated with children's weight and mental health outcomes. By increasing our understanding of how the COVID-19 pandemic has impacted the weight and mental health outcomes of children, this research will provide a much-needed basis for effective health interventions that support families with young children in managing stress and promoting healthy behaviours in the post-COVID-19 context.",2021,2022,University of Guelph,79395,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19696,202111WI1,"Impact of COVID-19 on Health Care Access, Utilization, Delivery, and Outcomes for Patients with Pulmonary Diseases in Alberta (INCLUDE Study)","The COVID-19 pandemic has profoundly impacted everyone, even those who have never had COVID-19. Both positive (greater accessibility via telemedicine) and negative consequences (less access to testing) on healthcare may have resulted. We suspect that patients with lung diseases have suffered worse healthcare experiences, access, and outcomes. Thus, we propose a multi-pronged approach to studying this issue: AIM 1: Health administrative data from Alberta will be analyzed to describe healthcare use and outcomes (e.g. hospitalizations and death) across a range of lung diseases. We will compare data from the 18 months before the pandemic to the 18 months after the pandemic started. This will demonstrate how utilization of healthcare resources has changed for patients with lung disease at the population level. We will also stratify these analyses by postal code (rural versus urban), sex, and socioeconomic data to determine if these factors are associated with any changes in health care use and outcomes. AIM 2: We will conduct surveys and interviews of healthcare providers and of patients with a broad range of lung diseases to understand how COVID-19 has affected healthcare delivery, access and utilization. Since patients with complex lung diseases are often marginalized and stigmatized, our focus on the patient experience will not only allow us to understand how COVID-19 has impacted their care, but also understand what has worked well for them. We anticipate that perceptions of the impact of COVID-19 (Aim 2) may be discordant with the administrative data findings (Aim 1). Thus, an integrative mixed-methods approach will allow a more complete understanding of the true impact of the pandemic on the health and wellness of patients with lung diseases in Alberta. This study is designed with the end knowledge users in mind (policymakers, academic and community healthcare providers) such that lessons learned can inform future health care policy to improve patient care.",2021,2023,University of Alberta,320128.54,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19697,202109EG2,Impact of COVID-19 on women and girls with disabilities in Canada: A life course perspective,"One in five Canadians 15 years of age and older have a disability, and women (24%) are more likely to have a disability than men (20%). Women with disabilities experience significant social, health, and health care disparities, including disparities in sexual, reproductive, maternal, and child health (SRMCH). These disparities are the result of a long history of eugenic practices imposed on people with disabilities, and lingering negative societal attitudes toward disability and sexuality. The United Nations has documented the global impact of COVID-19 on SRMCH due to diversion of resources away from SRMCH services. In Canada, impacts include restricted access to contraception and abortion; fewer available prenatal, breastfeeding, and parenting resources; high rates of maternal anxiety and depression; missed childhood routine vaccinations; suspension of in-person family access for children in the care of the child welfare system; and increased incidence of intimate partner violence. Such impacts have been felt more acutely in marginalized groups including racialized, low socioeconomic status, and rural/remote communities. However, one marginalized group for whom the impacts of COVID-19 on SRMCH have received little attention is women with disabilities. In partnership with the Disabled Women's Network (DAWN) Canada, we propose a study to examine the impact of the COVID-19 pandemic on SRMCH in women with disabilities across Canada using a national survey and interviews with women with disabilities in different stages across the life course. This research will result in real-time evidence to manage the impact of the COVID-19 pandemic on SRMCH in women with disabilities and ultimately build a stronger, more inclusive SRMCH service system as we look toward COVID-19 recovery.",2021,2022,University of Toronto,180059.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19698,202109EG7,Impact of COVID-19: Unmet needs for rehabilitation services among Canadians living with long-term conditions or disabilities,"Background: Rehabilitation services are considered an essential part of universal health coverage and an important strategy for achieving the United Nations' Sustainable Development Goal of ensuring healthy lives and well-being for all. In Canada, the delivery of rehabilitation services varies greatly depending on the severity and type of health condition, affordability, and accessibility. The COVID-19 pandemic has led to significant disruptions in the delivery of rehabilitation services. However, the magnitude and health impacts of these disruptions, and the resulting negative health outcomes remain unknown. Objective: We aim to investigate the magnitude, contributing factors, and self-perceived impacts of unmet rehabilitation needs during the COVID-19 pandemic. Methods: We propose a cross-sectional study using data from a national survey conducted by Statistics Canada between June 23 to July 6, 2020. We will include 13,487 Canadians living with a long-term condition or a disability. Individuals with unmet rehabilitation needs include those who reported that they needed rehabilitation (i.e., physiotherapy, chiropractic) but did not receive it due to the COVID-19 pandemic. We will use the information on demographic, socioeconomic, and health-related characteristics (e.g., age, gender, education, province of residence) to determine who was more likely to report unmet rehabilitation needs. We will use the self-reported measure of change in health to assess the possible deterioration in overall health during the COVID-19 pandemic. We will stratify all analyses by age, gender, and province. Significance: Our study will provide crucial evidence of the impacts of the COVID-19 pandemic on the access and delivery of rehabilitation to Canadians living with long-term conditions or disabilities, and to other marginalized populations. We will work with knowledge users to guide the planning of rehabilitation services in the extended pandemic period and future pandemics.",2021,2022,University of Ontario Institute of Technology,94833.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19699,202107UIP,Impact of COVID-related restrictions on maternal and infant health,"The rapid implementation of COVID-related policies and procedures across Canada were designed to reduce the spread of disease; but had far-reaching implications on maternal and child health. Prenatal, postpartum, and well-baby visits were transitioned from in-person to virtual visits (or cancelled outright by providers and patients as they tried to minimize exposure risk), universal forms of screening for gestational diabetes changed to a targeted screening model, infant immunization appointments (which traditionally had been used as broad health checks for the infant and their mother) transitioned to brief vaccine-only appointments, and length of stay in hospital for childbirth was reduced. As active case counts decline, and vaccine coverage increases, we are hopeful that we have now entered a recovery stage following the peak of the pandemic. This entails both a catch-up on missed services, but also a need to evaluate what policies and procedures had a beneficial impact and what should remain in place. In this study we will 1) describe the magnitude of missed screening and preventative health visits during pregnancy and the first year postpartum for pregnant persons and their infants; 2) assess how missed opportunities for preventative care differ by system factors (i.e., geography), community factors (i.e., area-level SES, ethnic concentration), family characteristics (i.e., presence of other children in the home, medical risk factors), and COVID-status in individuals (i.e., active infection during pregnancy) and the community (i.e., daily case count, type of restrictions); and 3) using an integrated KT approach, actively reach out to families who would benefit from enhanced follow-up.",2021,2022,University of Calgary,118500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19700,202203MM1,Impact of methodological decisions when conducting systematic reviews to inform decision making in the context of a pandemic,"After the COVID-19 pandemic started, many researchers focused on assessing treatments for this disease. Global and local authorities (such as the World Health Organization (WHO) and the Public Health Agency of Canada), as well as experts, used the emerging data to make recommendations. Because these recommendations were needed as soon as possible, the groups faced additional challenges beyond the usual in deciding how to best collect and summarize these data. Special challenges included the large amount of data available, the need for a process that was feasible and fast, and the availability of data that was published but had not undergone review by independent researchers. These potentially daunting challenges resulted in groups looking for innovative strategies that could increase their productivity by reducing the time and resources needed to collect the evidence. The risk was, however, that these strategies could increase the risk of introducing errors in the process. To date, no research group has studied the real impact of these strategies on the recommendations these groups made. We will use the data we have collected during the development of one of the largest projects that has collected and summarized the data regarding treatments for COVID-19, the ""COVID-19 Living Systematic Review and Network Meta-Analysis (LNMA)"". These data inform the development of recommendations by the WHO. Because we were unwilling to accept the risk of errors, we did not adopt the possible efficiency-enhancing strategies. Perhaps, however, we should have. To find out, we will re-analyze the data to explore if the results, conclusions, and WHO recommendations would have differed if we had used some of the strategies to increase productivity. Thus, we will provide evidence about the impact of such strategies that groups of experts can use in the future in scenarios in which they have limited time or resources to collect and synthesize the evidence.",2022,2024,McMaster University,253291.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +C19701,202111WI3,Impact of SARS-CoV-2 vaccination on women's reproductive health,"Women of reproductive age are often excluded from research studies on new interventions such as medications or vaccines. As a result, information on the safety of such interventions on female reproductive health outcomes is lacking. As SARS-CoV-2 vaccination became widely available in early 2021, so did concerns about the potential impact of vaccination on female reproductive health. Unsubstantiated claims were made on social media that the SARS-CoV-2 vaccine could damage the human placenta and result in infertility and miscarriage. This may have heightened vaccine hesitancy in some individuals. Pregnant people, and those who may conceive, are among those identified as having lower SARS-CoV-2 vaccine uptake. Furthermore, certain minority groups have raised concern about the long-term effects of SARS-CoV2 vaccination on fertility, which could be a contributing factor to their lower rates of vaccination. Well-conducted, population-based studies are urgently needed to understand whether there is any adverse effect of SARS-CoV-2 vaccination on women's reproductive health, with the ultimate goal of improving vaccine uptake, especially among identified high-hesitancy groups.",2021,2023,Queen's University,124820,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Adverse events associated with immunization | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19702,202107UIP,"Impact of Social Determinants of Mental Health on Child and Parent Risk, Resilience and Support Access in the COVID-19 Era: A Nested Mixed-Methods Study of Short and Long-Term Outcomes","Up until now, studies have suggested that 20% of Canadian children are impacted by a mental disorder. Social factors, such as an individual's sex and gender, race/ethnicity/immigrant status, economic position, geographical location (e.g., northern/rural), exposure to violence and the MH status of their parents influence youth's risk to, and resilience against, MH difficulties. These social factors also influence the extent to which children and parents can access support. The COVID-19 pandemic has already been found to have additional negative impacts on the MH of Canadian families; however, we have not yet identified which social factors contribute the most to MH difficulties and treatment access during the pandemic and subsequent recovery. In response, our team developed a research study that asked youth, their parents and other adults about their MH experiences during the pandemic. Between November 2020 and July 2021, we achieved recruitment goals and obtained 3,351 baseline responses including data on 1,502 children/youth and 1,198 parents. Our results indicate that MH disorders including major depression, generalized anxiety disorder and obsessive-compulsive disorder are affecting two to three times more individuals than has been estimated prior to the pandemic. Moreover, approximately one quarter of parents report needing, but not receiving, MH support for themselves or their children. The present study proposes to follow-up with individuals who completed the original survey and obtain more detailed information about their challenges, MH status, needs, care and support access during the pandemic, as well as social vulnerability and resilience factors. This will provide a perspective on change over time. As well, we will invite selected participants with identified vulnerabilities to poor MH outcomes to participate in focus groups and interviews that will allow us to collect more personal and detailed stories about Canadians' experiences and challenges.",2021,2022,University of British Columbia,87302.9,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19703,202107UIP,Impact of the COVID-19 pandemic on cancer care and outcomes in children and adolescents,"Cancer is a leading cause of death in children and adolescents in Canada. The COVID-19 pandemic is causing major disruptions to health care systems, and is likely to have negative impacts on cancer care in children and adolescents. Staffing shortages may occur due to reallocation of health care personnel to different services, or leaves of absence due to COVID-19 exposure. Many childhood cancers are diagnosed incidentally through routine health checks or for symptoms not initially thought to be cancer-related. Parents may be less likely to engage with the health care system for symptoms in their children in response to public health directives to stay at home, and fear of being infected with SARS-CoV-2 in healthcare settings. The pandemic is also likely to have created new psychological, social, and financial burdens for cancer patients and their families. Our research aims to study the long-term impact of the COVID-19 pandemic on cancer care and survival in children and adolescents. We will use health insurance medical claims, hospital records, and death registry data from Quebec to assess temporal changes in childhood and adolescent cancer diagnoses, survival, and treatment patterns attributable to the pandemic. We will also be performing a literature review of the psychological, social, and financial impacts of the pandemic on child and adolescent cancer patients and their families. While cancer is a rare disease in children and adolescents, it constitutes a leading cause of mortality in these age groups, and leads to a significant psychosocial impact on both patients and their families. As these cancers are rare, the analysis of data from large administrative databases is one of the best ways to assess the impact of the pandemic on child and adolescent cancer patients. Our results will be able to provide direct confirmation of whether public health directives to protect cancer services were successful in preventing negative outcomes in children and adolescents.",2021,2022,McGill University,113539.59,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19704,202111WI1,Impact of the COVID-19 pandemic on child growth and cardiometabolic risk,"The COVID-19 pandemic has had a profound impact on the daily life of Canadians, including children and parents. Child growth monitoring through primary care is an established practice to promote optimal growth, including the prevention of underweight and obesity. With the widespread and extended transition to virtual care during the pandemic, there have been limited opportunities for child growth monitoring. Evidence from recent studies and systematic reviews suggests that childhood obesity may have increased during the pandemic, but it is unknown if virtual primary care was a risk factor for this increase. In addition to changes in primary care availability, there have been unprecedented changes in obesity-related risk factors, including decreased access to recreation, increased screen time, increased exposure to stress, and socioeconomic hardships, including food insecurity. All of these factors may have increased the risk of adverse growth trajectories for both children and parents and potentially increased cardiometabolic risk, including dyslipidemia and high blood pressure. The overall aims of this study are to prospectively evaluate the changes in child growth from pre- to post-pandemic and to identify the risk factors associated with adverse growth patterns and cardiometabolic risk. We will conduct a prospective cohort study using extensive data collected pre- and mid-pandemic from TARGet Kids!. TARGet Kids is a primary care network in the Greater Toronto Area that was established in 2008 and includes more than 11,000 children. Our team has extensive experience with measuring child growth and cardiometabolic risk. This project will lead to important findings that will contribute to our understanding of the COVID-19 pandemic on children and parents and will identify opportunities for primary or secondary prevention initiatives to reduce the potential indirect long-term adverse consequences of the pandemic.",2021,2023,McMaster University,339467.74,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19705,202107UIP,Impact of the COVID-19 pandemic on mental health of children of parents living with mental illness,"Deterioration of mental health may be among the most serious consequences of the COVID-19 pandemic. Social isolation, lack of opportunities, unemployment and financial uncertainty are known triggers of depression, anxiety and other problems. Those living with pre-existing mental illness and their children may be among the most vulnerable ones to the indirect consequences of the pandemic. The development of children depends on the health of their parents. With intermittent school closures and reduced access to external resources, the wellbeing of children may be linked to the mental health of their parents even more strongly than before. Adolescents and young adults are impacted by the limited opportunities for social interactions, education, and work experience. As Canada emerges from the pandemic, it is imperative to plan services and supports for those who have been impacted. Effective planning depends on reliable information on which segments of the population are affected and what factors mitigate the impact. To provide such information, we will leverage a cohort of over 1000 children and parents from 300 families, including 200 families where one or both parents are living with mental illness. The parents and children provided detailed information on their mental health prior to the pandemic, in 2018-2019. Between May 2020 and June 2021, we recorded pandemic-related exposures, coping and impacts. Between fall 2021 and summer 2022, we will repeat the mental health and functioning assessments using the same measures that were used in previous assessments to find out which children and youth continue to be affected. We will examine how age, sex, gender, race, rural residence, income, parent health, continuity of mental health services, receipt of benefits, activities and coping influence mental health outcomes of children and youth. We team with the provincial government to apply the knowledge in the planning of services for children and youth.",2021,2022,Nova Scotia Health Authority (Halifax),118354.64,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19706,202107UIP,"Impact of the COVID-19 pandemic on obstetrical care and maternal, perinatal and early childhood outcomes in Ontario","A central goal of pregnancy care is to give children the best possible start in life through improving the health of mothers and identifying/modifying risk factors. The COVID-19 pandemic has resulted in profound system-wide changes in pregnancy care. Virtual care was rapidly introduced to reduce in-person prenatal visits, to reduce spread of infection. In the third wave of the pandemic, severe illness in pregnancy increased across Canada. In some cases, severe COVID-19 infection in pregnancy requires delivery of premature infants to improve the health of the mother; prematurity can have significant negative long-term health effects for children and their families. In response to the rise in severe illness in pregnancy, pregnant women were prioritized for COVID-19 vaccination. Vaccination in pregnancy and during breastfeeding may confer protection to children after birth, but the impact of vaccination on early childhood outcomes is not yet determined. The impact of (i) new patterns of pregnancy care, (ii) the burden of COVID-19 infection itself in pregnancy, and (iii) vaccine uptake in pregnancy on outcomes of children, is largely unknown. Further investigation is warranted to determine if changes in obstetrical care (eg. virtual care) may be safely continued in subsequent lockdowns and after the pandemic, and to evaluate perinatal and childhood outcomes after COVID-19 infection and/or vaccination in pregnancy. Increasing knowledge of the safety/ benefits of vaccination in pregnancy is important to inform decision-making. COVID-19 is not a socially neutral disease: marginalized populations are disproportionately affected with COVID-19 infection. Health outcomes of children born to affected mothers may inform interventions aimed to further reduce directly-related and indirectly-related health inequities for these children in Ontario. We will engage families of babies born prematurely during the pandemic to discuss supports that may improve their long-term outcomes.",2021,2022,Unity Health Toronto,118363.33,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Adverse events associated with immunization | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2021 +C19707,202111WI1,"Impact of the COVID-19 pandemic on routine childhood and other primary care immunizations in Ontario, Canada","Vaccines are one of the most important public health interventions to protect at-risk patients, such as children and older adults with comorbidities, from serious infections. The COVID-19 pandemic has made it difficult to provide health services as usual, including vaccines. Studies all around the world have reported declines in immunization coverage in 2020, but there is still limited data in Canada. Our team recently completed a project on the impact of COVID-19 on routine immunization coverage in children under 2 years old in Ontario, using primary care electronic medical records data from the UTOPIAN database from January 2019 to December 2020. Our study found that immunization coverage rates for children under 2 significantly decreased during the early period of the pandemic and only partially recovered during the rest of 2020, and that some subgroups of children experienced larger declines in coverage and should be prioritized in immunization catch-up interventions. Building on this work, we want to expand our analyses to trend the childhood immunization coverage rates from 2018 to 2021 and look at other immunizations routinely given in primary care settings. These include tetanus and measles vaccines for children 4-6 years old, tetanus vaccine for teenagers (14-16 years old), tetanus/pertussis vaccine during pregnancy, pneumococcal vaccine for adults > age 65, especially in adults with medical conditions like heart diseases, diabetes and lung diseases. We will also do a survey study and interviews with patients and parents to understand the barriers and facilitations to accessing vaccination services during the pandemic. We will generate evidence to understand the extent of the indirect health consequences of COVID-19 on routine immunization coverage for at-risk populations, to identify factors (individual, provider, community-level, etc.) associated with coverage gaps and to inform targeted interventions to catch-up or prevent immunization delays.",2021,2023,University of Toronto,196511.71,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research","Indirect health impacts | Medicines, vaccines & other technologies",2021 +C19708,202107UIP,"Impact of the COVID-19 pandemic on the psychosocial health of children with cancer, survivors, and family caregivers: A pan-Canadian study of issues and solutions","Although the impact of the COVID-19 pandemic on youth mental health is widespread, children with cancer (the most common life-limiting disease in Canadian children), survivors of childhood cancer, and their caregivers, sit in a particularly precarious position. Childhood cancer is a highly stressful life event marked by intense and difficult treatment decisions, impacts on mental and physical health, and increased financial burden on families. During the pandemic, children impacted by cancer and their caregivers have also been exposed to several changes in cancer care. For example, cancelled psychosocial support groups, and limits to the number of caregivers allowed to be present in the hospital during treatment (e.g., one caregiver per patient). These restrictions have likely further impacted the wellbeing of children and their families. However, no studies have evaluated the psychosocial and behavioural health consequences of the COVID-19 pandemic among Canadian children with cancer, survivors, and their caregivers. We want to hear directly from youth with cancer, survivors of childhood cancer, caregivers, and health care providers (HCPs) in childhood cancer care settings about the impact of the COVID-19 pandemic. Our study has four phases. In Phase 1, patients, survivors, caregivers, and HCPs from across Canada will complete online surveys. In Phase 2, we will interview some patients, survivors, caregivers, and HCPs from Phase 1. Together, these surveys and interviews will tell us about COVID-19 impacts on mental and physical health as well as childhood cancer care. In Phase 3, we will meet with patients, survivors, caregivers, HCPs, and organizational partners. Here we will decide the clinical, research, and health policies that are needed to prevent or alleviate negative health outcomes on youth impacted by cancer and their families, and how to optimize wellbeing in the next phase of pandemic recovery and beyond.",2021,2022,Concordia University,118302.5,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Caregivers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19709,202111WI4,Impact of the COVID-19 pandemic response on chronic disease management (CDM) and quality of life (QOL) among Indigenous and Black communities in Ontario,"The increasing burden of multimorbidity (MMB) has revealed challenges of the health system to adequately manage persons with ongoing care needs for chronic diseases (CD). CD and moreso MMB require regular care management (CDM) for patients' wellbeing, positive outcomes and quality of life (QOL). Patients are often faced with lack of care integration or access to adequate care. These issues can be exacerbated in black and indigenous populations, likely more severely impacted by the policy response to COVID-19 pandemic, in place under the auspice of social good. Appropriate CDM and support for people with CD are key to improving their overall health status. The ongoing pandemic has further demonstrated the importance of considering disease cooccurrence in risk factors assessment and care management. It has also highlighted the limitations of the system to adequately respond to increasing health and wellbeing needs and face competing priorities. In the midst of the pandemic, there were reductions in service offering to respond to the crisis. Inevitably, this impacted the care of those already having difficulty navigating the system for their ongoing health needs, including patients with cancer, diabetes, dementia, or ID. The objectives of the proposed research are to: 1.Assess & better understand the impacts of the pandemic policy response for people living with CD who are members of Black and Indigenous communities; 2.Learn about approaches offered for CDM during the pandemic, their success/challenges; 3.Provide recommendations for policy responses and care approaches that are informed by anti-oppressive and intersectional ways, overall and in future emergencies. We will use a mixed-method approach including a survey and interviews. The study will target NW Ontario, including rural areas and Indigenous communities, plus Black communities in the GTA. Data will include SES, access to care, QOL, HCU, CDM and challenges, successes both before and during the pandemic, etc.",2021,2023,Lakehead University,231768.62,Human Populations,Black,Unspecified,Rural Population/Setting,Indigenous People | Individuals with multimorbidity | Minority communities unspecified | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C19710,202111WI1,Impacts of COVID-19 on Preventive Primary Care for Young Children: Consequences and Innovations,"The COVID-19 pandemic has significantly disrupted access to health care for young children including shifts to include virtual care (by telephone or video), and long wait times for specialty care. Preventive care in young children involves regularly scheduled visits with primary care providers. Such visits are important for early detection of and intervention for various health problems, including early intervention for developmental delay, feeding problems, and growth, and addressing food insecurity and preventing injuries. We aim to understand the impacts of the COVID-19 pandemic on primary preventive care for young children (0-5 years old). We will also identify barriers and clinic-based innovations and family-led solutions to problems accessing preventive care during the COVID-19 pandemic. We will use data from primary care electronic medical records from Ontario and Quebec and study changes in the pre-COVID era (March 12, 2015-March 11, 2020) and during COVID era (March 12, 2020-March 11, 2023) in preventive care visits, child outcomes, and inequalities in these utilization and outcome measures. Primary preventive care in early childhood is important for prevention of future health problems. We will work with knowledge users to apply our study findings to inform health system planning, with the ultimate goal of mitigating potentially detrimental lifelong outcomes of missed or deferred care for young children.",2021,2023,Queen's University,395000,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19711,202111WI1,Impacts of the COVID-19 pandemic on the primary care of chronic conditions,"Family doctors and teams in primary care provide the majority of care for chronic diseases. The COVID-19 pandemic has interrupted routine primary care. It is important that people with one or more chronic diseases can access their family doctor for routine check-ups, adjustments to medications and taking blood pressure, etc. This ongoing monitoring helps manage their condition and avoid a flare-up that could lead to hospitalization. Since the pandemic, most primary care shifted to virtual care, where a doctor talks to a patient by telephone or video. In-person visits have been reduced. Many patients have been afraid to visit a doctor's office due to potential for infection, or they think their doctor cannot see them in person. This trend might have a negative impact on the management of chronic conditions. In this research, we will evaluate the impacts of COVID-19 on chronic disease care, using a large database that anonymously compiles the electronic medical record data from over 1500 family doctors' practices across Canada. We will look at conditions such as hypertension, diabetes, heart failure, and kidney disease, to evaluate changes in the detection and management of these conditions after pandemic restrictions began. We will examine whether changes disproportionately impact patients who are age 80 and older, with frailty, and if there are gender differences. To understand the reasons for gaps in care and possible solutions, we will interview patients with these conditions, and primary care physicians and nurses. We will ask about their experiences and what is most important to them for addressing chronic conditions, given that there may be a prolonged period of uncertainty in health care before things return to normal. This study will provide evidence on which specific aspects of primary care have been most impacted in the pandemic, and it will identify possible solutions to be recommended for recovering from the pandemic.",2021,2023,McMaster University,224810.3,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19712,202111WI1,Impacts of the COVID-19 Pandemic on Youth Mental Health Service Use,"The COVID-19 pandemic and related public health measures have affected many young Canadians. In particular, the pandemic led to changes that may have affected the use of mental health services among young people. This project will identify potential changes in service use for mental health reasons, why the changes happened, and if particular groups of young people were especially affected. We will use administrative health care data and interviews with decision makers, service providers, parents/caregivers, and youth. The results of the project can inform service delivery as Canada returns to a new 'normal' and guide potential responses to future pandemics.",2021,2023,University of Alberta,146624,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19713,202112FO1,Implementation and Evaluation of an Indigenous Virtual Patient Experience Tool in Response to COVID-19,"In response to the COVID-19 pandemic, rapid shifts in the delivery of primary health care (PHC) services to virtual care models occurred in Canada. Insufficient access to primary health care may undermine both the capacity to prevent transmission of COVID-19 infection, as well as effectively manage pre-existing chronic diseases. Moreover, relational factors necessary to provide high-quality PHC with Indigenous patients may be inhibited by virtual care provision. To address this gap our research team co-developed a virtual care Indigenous patient experience tool via a previous CIHR-funded project. This tool is oriented to monitoring and improving the quality of virtual PHC contacts with Indigenous patients. The next stage of this research is to evaluate and implement the tool with Indigenous health service partners. Informed by principles of implementation science, we will implement an Indigenous patient experience of virtual care tool with the Alberta Indigenous Virtual Care Clinic (AIVCC) to monitor and measure patient experience. Qualitative semi-structured interviews will be completed with patients and providers from the AIVCC to understand the acceptability and utility of the tool, and to understand barriers and facilitators to implementation. Specific implementation strategies will be determined through the completion of the interviews with additional qualitative interviews completed post-implementation to support a process evaluation. Anticipated strategies include the creation of an online infrastructure for the AIVCC to collect patient experience data and to generate a feedback report that the AIVCC can access on an ongoing basis and educational supports for clinic staff. This work will improve the ongoing virtual delivery of PHC with Indigenous patients arising from COVID-19 by providing methods to measure the quality of the virtual care encounter.",2021,2022,University of Calgary,188644.1,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19714,202005VR4,Implementation of serological and molecular tools to inform COVID-19 patient management,"Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a novel virus that causes COronaVIrus Disease 2019 (COVID-19). There is considerable variability in symptom severity and outcomes among patients infected by SARS-CoV-2. Linking genome and viral sequencing information to antibody (immune) response and other biological information (sex, age, ancestry, symptom severity, comorbidities, and outcome) may identify characteristics of patients that are associated with poor and favourable outcomes. This study will address three aims. Aim 1: Identify the characteristics of the antibody response that result in maintained immune response and better patient outcomes. Aim 2: Determine impact of genetic differences on COVID-19 infection severity and immune response. Aim 3: Determine impact of different viral strains on antibody response and patient outcomes. Patients with COVID-19 will be recruited from Sinai Health System, University Health Network, Baycrest Health Sciences and William Osler Hospital System. Patients seen in the emergency department with mild symptoms as well as hospital in-patients with more severe symptoms will be consented. Blood samples will be collected when patients are in hospital and 6 months and 1 year after COVID-19 diagnosis. Neutralizing antibody levels will be measured at all time points. Patient and viral genomes will be sequenced. Statistical analysis will be used to test for associations between antibody levels, genetic variation, viral genome variation, and patients' characteristics including age, sex, ancestry, comorbidities, and symptom severity. This study will link serological, genomic and patient characteristics to provide a comprehensive understanding of factors that contribute to variability in clinical symptoms and outcomes among COVID-19 patients. Evidence from this study will determine if immune response, viral strain and genome sequencing are effective for the diagnosis, prognosis and management of patients with COVID-19.",2020,2021,Sinai Health System (Toronto),1550398.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Pathogen genomics, mutations and adaptations | Prognostic factors for disease severity",2020 +C19715,202109EG7,Implementing a telemedicine and remote-mentoring platform to provide integrated noncommunicable disease and COVID-19 care in primary care facilities in rural Pakistan,"As the world struggles to contain the Covid-19 pandemic, the crisis has revealed a great deal about the gaps in global health systems, especially in the low- and middle-income countries (LMICs). Evidence shows that patients with non-communicable diseases (NCDs) are at higher risk of contracting Covid-19 and suffering direct and indirect consequences. Countries are using different digital health strategies and solutions to support the public-health response to COVID-19 worldwide, including virtual clinical care, population surveillance, case identification and contact tracing for management and control of NCDs during the COVID Pandemic. There is an urgent need to strengthen primary care to screen, triage and manage NCDs and at the same time to provide home and community-based solutions to prevent community transmission of COVID-19. All people under care for NCDs are priorities for COVID-19 vaccination education and provision; as well as for identification and care of possible COVID illness. Our study aims to implement an integrated package of care for NCD (mainly hypertension/diabetes) and COVID-19, via telemedicine and tele-mentoring platforms, in primary care facilities in rural Pakistan, and to evaluate its effectiveness using an implementation science framework. Our study is guided by the implementation science RE-AIM framework which tackles health system factors at multiple levels. We will implement the integrated NCD-COVID care in six intervention with six health facilities matched control ones through qualitative and quantitative research methods. The study will improve health services for NCD patients who have high risk to COVID. This study fits into CIHR's Global Health Policy as it aims to improve health equity for vulnerable NCD patients facing immense challenges to accessing quality care during the pandemic.",2021,2023,University of Toronto,394909.94,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Eastern Mediterranean,Eastern Mediterranean,Digital Health,,,Pakistan,Pakistan,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening","Indirect health impacts | Health service delivery | Medicines, vaccines & other technologies | Cross-cutting",2021 +C19716,202111WI1,Implications of changes to pediatric primary healthcare delivery resulting from the COVID-19 pandemic and the role of virtual care.,"The COVID-19 pandemic triggered widespread changes in the delivery of pediatric primary care. Many primary care practices functioned at reduced capacity or switched to mainly virtual modes of care delivery. Families reported difficulty accessing timely primary care when their child was sick and barriers to receiving important preventive care, including immunizations and developmental surveillance. Further, emergency departments reported difficulties managing the many children who might otherwise be seen in pediatric primary care. Leading healthcare organizations, providers and policy-makers are challenged to promote the right balance of in-person and virtual care while maintaining high quality, timely, and accessible care. There is little existing evidence on who should be seen in-person and for what conditions while considering the convenience and other potential benefits of virtual care. Our study aims to understand the impact of the pandemic on the performance of the primary care system with the shift from in-person to virtual care. We will use data from Ontario's children to measure the extent to which virtual vs. in-person primary care delivery is associated with 1) care accessibility, as measured by after-hours access and inappropriate use of emergency departments for low urgency concerns, 2) population health outcomes, including the timely identification of developmental and health concerns, and 3) quality, safety and patient centredness of care. We will specifically examine how these outcomes vary by primary care model (e.g., fee-for-service, comprehensive care models) and in those at risk for barriers to care including refugees, those living in rural areas, and families with high social risk (teenage mothers, parental mental illness, low-income). This research will inform guidance on how best to incorporate virtual care in pediatric primary care for Canada's 7 million children and adolescents while ensuring it is high quality, accessible, and equitable.",2021,2023,Hospital for Sick Children (Toronto),253176.83,Human Populations,Unspecified,Adolescent (13 years to 17 years),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19717,202108VCF,Improving COVID-19 Vaccine Confidence and Uptake among Black Canadians,"Black Canadians have the highest rates of COVID-19 infection and death in Canada. Black Canadians also have the lowest COVID-19 vaccination rate in Canada. Two national surveys indicate Black Canadians are 20% less likely than White Canadians to receive the COVID-19 vaccine. Some factors that contribute to COVID 19 vaccine hesitancy include lack of trust in healthcare professionals, lack of trust in vaccines, younger age, being female, low education, and being unable able to take time off from work. Improving the COVID-19 vaccination rate among Black Canadians is of high interest to policy makers and stakeholders. Our project seeks to address knowledge gaps related to COVID-19 vaccine confidence and uptake among Black Canadians and inform effective strategies to improve COVID-19 vaccine confidence and, in turn, uptake among Black Canadians. We will use a participatory research approach and consider diverse social determinants, including gender, socioeconomic status, and race/racism, throughout our data collection process. The project will be conducted in four phases. Phase 1 will involve interviews of Black Canadians. Phase 2 will involve a scoping review of the literature. Phase 3 will involve focus groups with stakeholders. Phase 4 will involve taking action through the co-development of knowledge translation tools. We will thematically analyze our qualitative data. Our project will result in the creation of a practice guideline, a policy guideline, and an e-learning module on strategies to address COVID-19 vaccination among Black Canadians. Our interdisciplinary team of experts in Black people's health, infectious disease control, qualitative research, scoping reviews, immigrant health, and participatory action research is well positioned to address this knowledge gap.",2021,2023,University of Alberta,158000,Human Populations,Black,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C19718,202108VCF,"Improving Vaccine Confidence with Better Clinical Conversations: Expanding and evaluating a dynamic, clinician-driven, online guide for Canadian primary care","www.vhguide.ca](http://www.vhguide.ca)) which was launched in July 2021. That website supports PCPs in having conversations that will improve vaccine confidence (Funding Objective 2). Our team will conduct interviews that a) identify the origins of VH in marginalized groups; and b) draw out specific conversational approaches for effectively dealing with those types of VH. We will then iterate, improve, and evaluate the website using the material we gather in the interviews and from user analytics. Those analytics will be gathered in real time from the website as PCPs' use it, and through surveys asking about user experiences. The project will improve vaccine confidence and uptake.",2021,2023,University of Calgary,154040.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C19719,202112FO1,In Their Words: COVID-19 experiences of the Vuntut Gwitchin people of Old Crow,"Yukon University and the northern Village of Old Crow, led by the Vuntut Gwitchin First Nation (VGFN), is seeking a research operational grant to explore emerging issues during the COVID-19 pandemic. VGFN is a self-governing First Nation* who are progressive and innovative in relation to climate change, health and wellness, and economic sovereignty. They have taken numerous proactive approaches during COVID-19 to protect citizens by instituting controlled access to the community, and using a local risk matrix. Vaccine uptake is high with 86% fully-vaccinated citizens. This grant would support the community and Yukon University to reveal the impacts of COVID-19 on the citizens of Old Crow. The project will be led by a member of the VGFN government (co-applicant), the Scientific Director of the Yukon SPOR unit (NPI), a VGFN Knowledge Keeper, and a Sex and Gender champion at Yukon University. A community researcher will be hired from, and reside in Old Crow. The fundamentals of OCAP, UNDRIP and TCPS-2 will be at the forefront of the research. Research will be grounded in Indigenous Knowledge and lived experience, using culturally-appropriate, meaningful methodology. Stories and experiences of the First Nation citizens will be heard, privileging the voices of Elders, to explore the successes and challenges that arose these past two years. The community has stories of ancestral responses to previous epidemics/pandemics that remain. Indigenous Knowledge passed through generations has supported the resilience of First Nation people in Canada's north to thrive through centuries of challenges. Lessons from this community add depth and new learning to our western health systems. Though Old Crow faces challenges to the health and wellness of citizens, the strengths of this community and collective approach to COVID-19 may support a model for other rural/remote/northern and Indigenous communities in Canada. *11/14 Yukon First Nations are self-governed with signed land claims.",2021,2022,Direct Payment,182332,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement,2021 +C19720,202109EG7,Incidence and risk factors of inappropriate antibiotic prescribing and related adverse health outcomes among Ontario long-term care residents and marginalized older community-dwelling adults with COVID-19 (I-CARE),"It is rare for patients with COVID-19 to have a bacterial infection at the same time as their viral infection, especially among non-hospitalized patients. Despite this, antibiotics are frequently prescribed unnecessarily in these patients. One particular group that is at high risk for inappropriate antibiotic prescribing in COVID-19 is older adults. Older adults, especially those in long term care homes (LTCH), are also highly susceptible to the toxicity of antibiotics including downstream complications such as Clostridioides difficile infection (CDI) and antimicrobial resistance (AMR). Marginalized older adults who do not live in LTCHs may also receive inappropriate antibiotic therapies and experience related adverse health outcomes during COVID-19 in Canada. To address these emerging concerns, we aim to study institutionalized and community-based older adults (66+ years of age) with confirmed COVID-19 to estimate (i) how frequently inappropriate antibiotics are prescribed and why, and (ii) how often complications including CDI and AMR occur, and what proportion of these complications are due to inappropriate antibiotic use. A particular focus with the community-based cohort will be whether neighbourhood-based aspects of marginalization (i.e., residential instability, material deprivation, dependency, and ethnic diversity) modify these impacts. We will rapidly perform two separate retrospective cohort studies, using existing linked clinical and administrative databases available in Ontario (ICES), to generate real-time evidence for accelerated sharing with government and public health stakeholders to improve our management of COVID-19. Our results will directly inform the equitable care of vulnerable populations and will evaluate the ongoing impact of COVID-19 on health systems and services by identifying risk factors for inappropriate medication prescribing and associated harms.",2021,2022,Ottawa Hospital Research Institute,244034.16,Human Populations | Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research",Disease pathogenesis | Indirect health impacts | Health service delivery,2021 +C19721,202112FO1,Indigenous Approaches to Wellness & Psychotherapy as a Response to the COVID-19 Mental Health Crisis in Indigenous Communities,"The COVID-19 pandemic has seen a dramatic increase in rates of mental health issues, overdose, suicide, and violence in Indigenous communities in Canada. Existing mental health services are inadequate in addressing this mental health crisis, particularly given the general ineffectiveness of mainstream approaches to mental health in Indigenous communities. Numerous studies and reports are calling for community-driven approaches to wellness and psychotherapy that support Indigenous communities in culturally relevant ways, yet many communities do not have the resources to support such approaches. In response to this literature and the immediate needs of communities in central Alberta, community stakeholders from the Rocky Mountain House region of Alberta are requesting support bringing in Indigenous psychotherapy alongside traditional wellness practices. The current study will explore community members' experiences of Indigenous Focusing-Oriented Therapy as they complete the program, and will further explore the development, implementation, and impact of community-driven cultural wellness programs in addressing the COVID-19 mental health crisis in the Rocky Mountain House region. Research conversations and focus groups will explore the impact of IFOT and cultural wellness programs on the COVID-19 mental health crisis in these communities. Findings will inform development of community-based wellness responses to the COVID-19 mental health crisis that incorporate both traditional approaches to wellness and Indigenous psychotherapy. Themes will be used to develop a framework that other Indigenous communities may draw on in creating effective community-based health initiatives. This research directly supports community-based capacity to respond to mental health crises, and will provide a foundation for further research to investigate the effectiveness of IFOT and cultural programs in addressing the mental health needs of Indigenous communities.",2021,2022,University of Calgary,197500,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Social impacts | Community engagement,2021 +C19722,202112FO1,"Indigenous food sovereignty community wellbeing amidst a pandemic. Activating Cwelcwelt Kuc - "" We are Well"" through transformational learning in a network of community covid care - upholding a decolonizing model to Indigenous health food sovereignty.","Growing evidence demonstrates that in the present health care system, traditional wellness and healing practices rooted in ancestral knowledge and land-based pedagogies are enabling factors that promote Indigenous peoples' sense of wellbeing (Fiedeldey-Van Dijk, 2017; Sasakamoose, et al, 2017). Specifically, traditional women's teachings and ecological knowledge, water and health revitalization, land-based pedagogies, and food sovereignty are considered to be important contributing factors to health and well-being (Bruyere et al, 2020; Redvers, et al 2020 & Sanderson, et al., 2020). This CIHR funded project will conduct an Indigenous, community-centered, evaluation of the Indigenous Food and Freedom School (IFFS) and its ability to strengthen community-level well-being and resilience in the face of COVID-19. The project will apply the decolonizing food systems transformative framework developed by the Working Group on Indigenous Food Sovereignty (WGIFS) to promote culturally safe practices in a community of practice. This project aims to operationalize our vision of 'A just transition to a regenerative tribal economy informed by Indigenous food sovereignty, paradigms, principles and protocols.' The IFFS was initiated by the WGIFS in April 2019 to develop programs, policies and interventions for a cohort in Chase, Secwepemc, to expand Indigenous food system networks and economies of solidarity and mutual aid. The project will apply Indigenous land-based pedagogies and a trauma/genocide-informed approach to develop, test and evaluate a series of intra-active activities, and regeneration, health and wellbeing of communities of focus where lack of adequate housing makes social distancing or quarantining an issue.",2021,2022,Thompson Rivers University,197081.3,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C19723,202112FO1,Indigenous Led Responses to Intersecting Pandemics,"Pandemic experiences are not new to Indigenous Peoples of North America; introducing and spreading infectious disease was a strategy of colonizing nations to claim lands and resources without resistance. CAAN - Communities, Alliances, and Networks are leaders in responding to HIV and AIDS in Indigenous communities in Canada with a mandate to lead and support research relevant to Indigenous organizations and communities impacted by HIV, Hepatitis C (HCV), tuberculosis (TB) and other co-infections. We witness Indigenous Peoples navigating ongoing and layered syndemics every day. For this reason, CAAN's research mandate is strengths-based, culturally safe, and grounded in Indigenous knowledges and solutions. CAAN's research with Indigenous-led front-line service organizations responding to HIV, HCV, and TB lays a foundation to sustain a response to the continually evolving COVID-19 situation and its consequences for intersecting pandemics. We know the experiences of working through other 'demics' informs organizational and personal responses to COVID-19 and we aim to understand how to identifying practices and processes others may find useful as well as to provide space for reflection and integration of the full experience, which may include layers of tragedy and grief. This is the lived experience of front-line work even without a global pandemic; we intend to bring to the fore what can be learned from the people serving in these contexts every day in support of the organizations and to highlight the staff wisdom. The research will support identifying, implementing, and sharing culturally safe, Indigenous community-led solutions to address the COVID-19 pandemic and its consequences by addressing the research areas of culturally safe covid-19 prevention, preparedness, response (and recovery) for indigenous peoples. Our research is supported by Indigenous-led front-line organizations in Halifax, Toronto, Thunder Bay, Regina, and Red Deer.",2021,2022,"Communities, Alliances & Networks (Vancouver)",150024.16,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19724,202107UI1,Indigenous People's response to the Covid-19 pandemic: Conceptualizing concepts of risk and health through an Indigenous midwifery-led approach,"How do pregnant Indigenous Peoples in Ontario conceptualize health and risk before and during the COVID-19 pandemic in the context of maternity care? Using Indigenous feminist theory, Indigenous feminist methodology, qualitative interviewing using an open-ended questionnaire with Indigenous participants who have or will experience evacuation for birth before or during the COVID-19 pandemic, we will: 1) Investigate how Indigenous Peoples who are pregnant conceptualize pregnancy related health and risk and how this informs their navigation of public health measures before and during the COVID-19 pandemic. 2) Document the strategies employed by Indigenous Peoples to maintain their spiritual, emotional, physical, and mental health and wellness when facing evacuation for birth and how this has been affected by the COVID-19 pandemic. 3) Explore the effects of the COVID-19 restrictions in relation to evacuation for birth and their impacts on the cultural webbing of Indigenous communities in Ontario during pregnancy and the postpartum period. Our research team, comprised of scholars, Indigenous midwives, and health policy analysts will address a gap in our knowledge about the weighing of risk Indigenous Peoples undertake when accessing healthcare systems and how this affects both their cultural fabric and health-related decision-making process. This proposal builds on research conducted in the spring of 2021 regarding the impact of the pandemic on evacuation for birth in Ontario, that concluded Indigenous Peoples in Ontario receive substandard care, care that is jeopardized by complicated, disconnected healthcare systems. The research will be led by an Indigenous NPA with strong Indigenous leadership and will contribute knowledge to further the meaningful development of maternity care policies and programming that is reflective of the experiences of Indigenous Peoples who live in and access maternity care in Ontario during the COVID-19 pandemic.",2021,2022,Queen's University,117296.83,Human Populations,Other,Adults (18 and older),Unspecified,Indigenous People | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Indirect health impacts,2021 +C19725,202109EG1,Inequities in COVID-19 Outcomes: the Mitigating Role of Public Health,"The COVID-19 pandemic has impacted socio-demographic groups differently, which can lead to widening health inequalities. For example, researchers have observed that people from low socioeconomic status and racial minority populations are more likely to be adversely impacted by COVID-19. The overall goal of this project is to estimate the extent to which public health funding, services, and programming aimed at decreasing social inequities during the pandemic has mitigated the risk for COVID-19 infection, hospitalization, mortality, and being unvaccinated, particularly among people from historically excluded populations.",2021,2022,University of Alberta,185650,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C19726,202107UIP,"Informing the pediatric mental health recovery plan: evaluating delays to diagnoses and changing characteristics of children and adolescents with new neurodevelopmental and mental health disorders in Ontario, Canada during the COVID-19 pandemic.","Neurodevelopmental and mental health disorders frequently emerge and are diagnosed in childhood and adolescence. Early detection and treatment are critical to ensure optimal health outcomes across the lifespan. During the COVID-19 pandemic, widespread closures of in-person activities and learning for children and adolescents as well as changes in access to health care have posed new challenges for early identification of neurodevelopmental (e.g. developmental delay, autism spectrum disorder, and attention deficit hyperactivity disorder) and mental health disorders (e.g., mood, anxiety, psychotic, substance use, eating, and other mental disorders). In addition, pandemic-related stressors (e.g., loss of connection with peers, increased screen time, reduced physical activity) may have triggered or worsened symptoms of mental health disorders among those who have not previous sought care. With our mental and developmental health systems already at capacity, the consequences of population-wide delays in diagnoses and shifts in who is affected and for which mental health disorders during a critical window of development may have profound implications on service provision needs downstream following the pandemic. Using well-established linked administrative and health datasets in Ontario, our study aims to understand the extent of delays to diagnosis and changing socio-demographic (e.g. age at diagnosis, sex, social vulnerability) and clinical characteristics (e.g. type of disorder, acuity of presentation) of children and adolescents with new neurodevelopmental and mental health disorders during the pandemic. We will compare the rates and characteristics of all children/adolescents with new diagnoses of neurodevelopmental and mental health disorders in the two years before and after the onset of the COVID-19 pandemic. This information is critical to informing our pandemic recovery plan across health, education, and community sectors to ensure adequate and targeted supports.",2021,2022,Hospital for Sick Children (Toronto),115968.84,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19727,202002OV3,Innovative therapeutic approaches for the 2019-novel coronavirus,"The 2019-novel coronavirus (SARS CoV-2) is a major sanitary and economical threat to all countries. Development of effective antivirals is a major global priority especially early in the epidemic when vaccines are unavailable. This proposal aims at discovering and evaluating active compounds by rational design through 3D modeling of key viral proteins and also by analyzing cellular gene signatures induced by the virus. In-depth evaluation of selected compounds will include in vitro, ex vivo (human bronchial epithelium tissues) and in vivo (animal models) studies. These approaches, mostly based on drug repurposing (new indication for an existing drug), will result in rapid identification of anti-SARS CoV-2 compounds with accelerated clinical development.",2020,2022,Université Laval,671182.5,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19728,202111WI1,Intensive Virtual Treatment with Remote Abstinence Monitoring for Alcohol Use Disorder,"The COVID-19 pandemic has had major impacts on both alcohol use and access to alcoholism treatment. For example, roughly a quarter of Canadians report increased alcohol consumption during the pandemic and there has been an increase in alcohol-related deaths among younger Canadians. At the same time, there has been a reduction in access to residential treatment (commonly known as rehabilitation or ""rehab""), with evidence suggesting that the pandemic has led to greater delays in accessing residential treatment and poorer treatment retention. The transition to virtual care that has occurred during the pandemic offers the opportunity for high quality intensive care without the need for admission to a residential facility. The goal of the proposed pilot project is to assess the feasibility of a virtual intensive outpatient program for alcohol use disorder that aims to replicate the structure and abstinence monitoring of a residential treatment program. This virtual 4-week program at its core will consist of a 12-session manualized group cognitive behavioural therapy (delivered as 3 sessions per week) that has been demonstrated to reduce alcohol use. Participants will meet at least once per week with an addiction physician to ensure adequate medical management. Participants will be given Soberlink breathalyzers, which utilize facial recognition technology and internet connectivity to remotely monitor alcohol use. Individuals who are struggling to maintain abstinence will receive more intensive individual care (including more frequent physician and/or individual therapy appointments) during the program. Building an intensive virtual care program with remote abstinence monitoring offers the opportunity to address treatment barriers that have occured due to the pandemic by allowing high quality alcoholism care to be delivered at home. Furthermore, this program will reduce the need for brick-and-mortar facilities with 24/7 staffing requirements.",2021,2023,Centre for Addiction and Mental Health (Toronto),393984.06,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19729,202107UI1,Inuit Youth and Families During COVID-19: A Strengths-Based Focus on Resources Needed to Optimize Post-Pandemic Resilience.,"How the COVID-19 pandemic has affected Inuit youth in Nunavut is not yet well understood. Enduring effects of colonialism, infrastructure inequalities, geographic isolation, and loss of cultural identity may make Inuit youth more vulnerable to the psychological effects of COVID-19. In this research, we are hoping to support Inuit youth in sharing what the impact of this pandemic has been on their own and their families' mental wellness. We are further hoping to invite youth to identify the culturally specific personal and community resources they relied on to get through the many restrictions that were imposed in the pandemic. This information, as well as the youth's reports on COVID-19 related challenges and needs, would provide input on useful tools and services that could be offered to communities in post-pandemic efforts to best support resilience. The proposed study builds on recommendations provided by youth who participated in a recent small pilot study which identified multiple facets of youth and community resilience. In that preliminary study, youth highlighted the notion of connection as being an important concept leading to resilience when physically isolated. This study would 1) Add to our limited understanding of the psychosocial impact of the COVID-19 pandemic 2) Design, together with youth leaders, a way to identify a comprehensive list of cultural and community aspects of connection believed to contribute to resilience: several culturally sanctioned research approaches will be considered in consultation with the youth. 3) Investigate additional and alternative ways of creating connection in a technological age. 4) Identify, together with youth, existing as well as wished-for social structures and systems that may further support connection and resilience during a pandemic. 5) Situate resulting findings in a culturally-embedded philosophical framework-Inuit Qaujimajatuqangit (IQ)-to allow for a richer and more accurate understanding of resilience.",2021,2022,York University,118500,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19730,202109EGB,Investigating COVID-19 Vaccine Outreach Strategies for Marginalized Newcomer Communities,"The COVID-19 pandemic has negatively affected low-income communities in Canada. These communities have more immigrants, refugees, and temporary foreign workers (together called 'newcomers') who often work in frontline essential jobs and have lower COVID-19 vaccination rates. This increases the risk for more COVID-19 infections, hospitalizations, and deaths - especially as the more infectious COVID-19 Delta variant spreads. Research shows that newcomers face many barriers to vaccination, are more vaccine-hesitant, and have more difficulty getting COVID-19 related information from trustworthy sources. Alberta currently has the lowest COVID-19 vaccination rates and highest COVID-19 infection rate in Canada, increasing the risk to unvaccinated newcomers. To improve vaccination rates among newcomers, our team members developed different outreach vaccination strategies including 1) onsite meat plant vaccine clinics for workers; and, 2) targeted community-engaged vaccination clinics (i.e., mass, pop-up and mobile bus clinics). We will build directly on our already established COVID-19 research team and benefit from the goodwill and trust built by our community-partnered team to study how different vaccine outreach strategies for newcomers may help build vaccine trust and overcome vaccine hesitancy. We will study: 1) How COVID-19 vaccine outreach clinics may help overcome vaccine hesitancy; and, 2) Reasons for vaccine acceptance and hesitancy among unvaccinated newcomers. Our embedded mixed-methods case study will collect and study surveys and interviews with vaccinated and unvaccinated newcomers. We will then combine our data and use them to make recommendations to improve newcomer vaccination outreach programs. With COVID-19 vaccinations for children under 12 years expected soon, understanding the best vaccination strategies for vulnerable communities will help Canada and other countries improve vaccine delivery, protect vulnerable communities from COVID-19.",2021,2022,University of Calgary,370695.65,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19731,202111WI2,"Investigating the impacts of social isolation on long-term care residents' cognition, function and mood during the COVID-19 pandemic","Residents of long-term care homes in Canada have been the most hard-hit by the COVID-19 pandemic and have experienced significantly higher numbers of cases and deaths compared to the general population. Since the beginning of this pandemic, long-term care homes in Ontario have been operating under varying degrees of lockdown or restrictions aimed at preventing the spread of COVID-19. These public health restrictions have put drastic limitations on residents' social interactions, including stopping family members, volunteers and non-essential personnel from entering homes, reducing or cancelling social activities within the homes, restricting communal dining, and at times isolating residents in their rooms for days to weeks. While these efforts have been aimed at protecting residents' health, there are growing concerns that they have had consequences on resident health and well-being by reducing residents' social engagement and increasing their social isolation. In this project, we will evaluate the wider impact of the COVID-19 pandemic on the cognition, function, and mood of long-term care residents in Ontario. We will describe the social isolation experienced by long-term care residents throughout the first year of the COVID-19 pandemic, including isolation related to pandemic-related public health restrictions (e.g., lockdowns and visitor policies) and infections. We will compare changes in cognition, function, and mood in long-term care residents before and during the COVID-19 pandemic. Finally, we will evaluate how social isolation, along with other resident, home, and system characteristics were associated with patterns of decline in cognition, function and mood. Our overarching goal is to enable better pandemic planning and management in long-term care settings while prioritizing the overall health and well-being of residents.",2021,2023,Bruyère Research Institute,291451.54,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19732,202109EG7,"Investigating the mental health and resiliency of key Canadian health professionals involved in primary, secondary, and tertiary prevention amid the COVID-19 pandemic: A qualitative study to identify and understand work stressors among medical laboratory technologists, pharmacists, occupational therapists, and physiotherapists, and lessons learned to optimize quality of health care","Canadian health care workers have felt the mental health impact of COVID-19. However, little is known about key health care providers who have been instrumental in the fight against the pandemic in hospitals, laboratories, and outpatient settings, such as medical laboratory technologists (MLT) and assistants (MLTA), pharmacists, and rehabilitation specialists (i.e., occupational therapists and physiotherapists). In fact, there is limited research on them pre-pandemic. However, what we know is with increased workload and stress, they have higher rates of burnout, sick leaves, and errors. These outcomes affect our health care system and patient safety. Therefore, we began with initial studies based out of Ontario. One was a mix-method study (questionnaire and focus groups) examining the psychosocial well-being of MLTs and MLTAs. The others were qualitative studies where we interviewed pharmacists to learn about their stressors and resiliency. The results showed that work stressors have been occurring well before the pandemic but have been felt to a greater extent, especially among caregivers. Also, it highlighted these groups' important role in supporting Canada's most vulnerable people, like older adults and patients with multiple health conditions. They also offered strategies to continue supporting vulnerable patients during lockdowns. We aim to expand our work to a national level based on these initial findings and include rehabilitation specialists. We will conduct semi-structured focus groups with employees from each occupational group through our established partnerships across Canada. We will explore common occupational stressors and discuss the 'lessons learned' while working during the pandemic to improve services across the country. We will analyze the data and provide key recommendations to help inform policies and improve health care quality across the country.",2021,2022,University of Guelph,94871.1,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C19733,202111WI1,"Investigating the mitigating role of Public Health on suicide, drug poisoning, and alcohol-related harm in Ontario, Canada during the COVID-19 pandemic.","In addition to the rise of morbidity and mortality due to the COVID-19 pandemic, spillover adverse effects on population health have occurred. Preliminary research has indicated that increases in suicides attempts, drug overdoses, and excessive alcohol consumption are adverse consequences of the pandemic. Furthermore, the pandemic has had a disproportionate impact on a number of socio-demographic groups, potentially leading to widening health inequities, and thus further raising public health concern. For example, racial and ethnic minorities, people from lower socioeconomic (SES) backgrounds, and adolescents may be at greater risk for suicide, drug overdose, and excessive alcohol consumption. The overall goal of this study is to estimate the extent to which public health services during the pandemic has lowered the risk for suicide attempts, and drug and alcohol poisoning and deaths attributed to these conditions. Furthermore, we will determine if people from racial/ethnic, lower SES status backgrounds, and adolescents are more likely to benefit from public health services, thereby shrinking health disparities. To answer these important research questions, we will use unique datasets, including the Ontario Public Health Information Database (OPHID), developed by our team, and the Ontario Health Data Platform (OHDP) to assess the association between public health funding, programming, and services, and suicide, and drug and alcohol harm in Ontario, Canada. Specifically, we propose to: 1. Describe how the COVID-19 pandemic has impacted public health funding, and services, and staffing geared towards prevention of suicide, and drug and alcohol poisoning, across local Public Health Units (PHUs) in Ontario. 2.Estimate the associations between PHU programs, resources, and services and risk for suicide attempts, and drug and alcohol poisoning. 3.To determine whether observed associations are heterogeneous across race, SES status, age, and urban vs. rural residency.",2021,2023,University of Alberta,243715,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Drug users | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19734,202107UIP,Investigating the potential mitigating role of public health on adolescent health in Ontario during the COVI9-19 pandemic,"Before the COVID-19 pandemic, mental and sexual health conditions among Canadian youth have been a concern to both public health researchers and school administrators. High proportions of depression and anxiety, as well as increasing chlamydia and gonorrhea rates have raised the alarm. During the pandemic, public health restrictions, such as school closures, social distancing, and stay at home orders may worsen these mental and sexual health issues, particularly during this important stage during their development. The goal is to estimate the extent to which disruptions to public health services during the COVID0-19 pandemic has impacted mental and sexual health among Ontario youth. We will also determine whether disruptions disproportionately affected youth across different gender and racial groups.",2021,2022,University of Alberta,118500,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19735,202109EG8,Is TikTok Changing the Way Young People Learn about Mental Health and Connect to Health Services During the COVID-19 Pandemic?,"Where does the health system begin and end for young people living in Canada? Early in the COVID-19 pandemic, there was a surge in TikTok users as young people sought to cope with boredom during lockdowns (total monthly users n=1.1 billion, 7/10 teens in Canada report using TikTok). Besides viral dance videos, TikTok's short-form video platform and less visible algorithms gives young people a place to learn about mental health, connect to peers struggling with similar challenges, and de-stigmatize seeking care. TikTok creates a place to effectively meet the needs of diverse youth suffering from mental health and substance use challenges during the pandemic, including populations historically excluded and underserved. The next step is understanding how to leverage TikTok to effectively develop and implement mental health interventions and services to connect young people to care, improve outcomes, and optimize patient experiences. From the perspective of youth living in Canada, the objectives of this study are to (1) assess the quality of mental health information and advice on TikTok during the COVID-19 pandemic, (2) elevate the voices of diverse young people to understand how Canadian youth navigate TikTok during the pandemic to learn about mental health and connect to services. This project will use multiple methods including (1) content analysis of TikTok videos tagged with #mentalhealth, (2) sentiment analysis to determine if content is positive or negative, and (3) qualitative interviews with 30-40 diverse youth from across Canada to understand barriers and facilitators for using TikTok to navigate mental health information and services. The output will be a youth-centred model for how best to communicate to youth about mental health through TikTok and youth friendly and community relevant options for accessing care during and after the pandemic.",2021,2022,University of British Columbia,282637.51,Human Populations,Other,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19736,202002OV7,"kitatipithitamak mithwayawin: Indigenous-Led Countermeasures to Coronavirus (COVID-19) and other Pandemics Then, Now, and Into the Future","The 2019 Novel Coronavirus (COVID-19) was first identified on December 31 2019 in Wuhan, China. As of February 18 2020, 73,439 COVID-19 cases have been confirmed in 29 countries around the world with an attributed 1,875 deaths. The World Health Organization recently declared COVID-19 as a global health emergency. Studies on H1N1 and other pandemics show that Indigenous communities in Canada suffered most from these diseases. Responses to H1N1 were often inadequate and at worst created more harm than good. Communities had poor access to medical experts and supplies. Indigenous organizations were mostly excluded from decision-making. And misinformation generated much fear that still persists today. Yet, many Indigenous communities and organizations also responded effectively and, with others, eventually found ways to reduce the impacts of H1N1. The outbreak of COVID-19 thus represents a critical moment. On one hand the same mistakes could be made, with similar impacts. On the other hand, there is an opportunity to do things differently in ways that are grounded in the priorities of Indigenous communities and organizations. The goal of this project is to evaluate the implications of past and existing responses to pandemics with respect to Indigenous communities across Canada and to address any gaps in understanding and support related to COVID-19 and future pandemics. This collaborative project will focus on the past by documenting experiences with other pandemics and explore changes in response over time. It will focus on the present by assessing current state of community emergency planning and risk communication. Finally, it will focus on the future by assessing community responses to different possible scenario and ideas for moving forward. We will share our outcomes with Indigenous communities and organizations across Canada, all levels of governments, and the general public so that the health interests of Indigenous people are best served now and into the future.",2020,2022,University of Manitoba,375000,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement,2020 +C19737,202005CMS,Knowledge Synthesis to Support and Promote Mental Wellness and Resiliency during the COVID-19 pandemic,"There are currently no vaccine or cures for COVID-19. As a result, our government recommends isolation, quarantine, and other measures to control the virus. However, when people isolate for a long time, their mental health may suffer. Some people with no mental illness, for example, may develop anxiety or depression, with symptoms that can last a long time. Others who are already living with mental illness may experience worsening symptoms, and at the same time experience difficulties accessing their usual health care or social supports. It is therefore important to support the mental health of the population during a pandemic. In line with this, our team of researchers, mental health professionals, and people with lived experience, propose to conduct a rapid review of the evidence on home activities and resources that can support mental health during times of isolation. We also propose to conduct an online survey to understand what activities or resources people prefer and will most likely use. Upon completion, study results will be shared with the government, CMHA and the CIHR. We will create a public website to share the results, with selected examples of effective home activities or resources. A research paper will also be submitted for publication. The results of our study will complement government plans to address the mental health impacts of COVID-19. It will work well, for instance, with the virtual mental health platforms that the government is planning to fund with $240M. We plan to update the project website with new evidence and examples from the literature as they become available so that the website continues to be a useful resource even long after the pandemic is over.",2020,2020,University of British Columbia,36088.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19738,202111WI1,Knowledge to Action in Pediatric Emergency Care during the COVID-19 Pandemic,"Information about COVID-19 in children changes fast as we learn more about the disease and its wider impact. This pandemic is changing the lives of children who have COVID-19 and in other ways. For example, the fear of getting COVID-19 may be changing how families decide on where and when to get health care. Children coming to the emergency department during the COVID-19 pandemic have been sicker. Most children when they need emergency care in Canada first visit a general or community emergency department that is not part of a children's hospital. It is important that healthcare providers in these emergency departments have the latest information on how best to care for children. Our research project will bring world-leading child health researchers, parents, and emergency healthcare providers together to share the latest information on COVID-19 and its wider impacts. We will use this information to create educational tools and resources so healthcare providers can quickly find and use the information they need when caring for children. Then we will test how useful these resources are for healthcare providers and if we need change them in any way. We will also ask parents and youth about what information is important for emergency healthcare providers to know. We will share these educational tools and resources will all emergency departments in Canada. We want to help emergency health care providers feel better prepared to give the best possible care to children during this pandemic, and ultimately improve emergency care for children across Canada.",2021,2023,University of Manitoba,342694.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Health Systems Research | Research on Capacity Strengthening,"Supportive care, processes of care and management | Health service delivery | Systemic/environmental components of capacity strengthening",2021 +C19739,202111WI2,Laying the groundwork for improved psychological preparedness and adaptation of Canadian nurses working during healthcare crises: Simulated training to improve resiliency of nursing groups (STRONG),"The COVID-19 pandemic has had a devastating impact on Canadian nurses. Succeeding waves have led to increased levels of depression, anxiety, traumatic symptoms, and burnout among nurses. Staff shortages are now being reported as nurses change units, change workplaces or leave the profession. However, anecdotal reports suggest that enrollment in Canadian nursing programs is higher than it was pre-pandemic. Previous research has shown that new nursing graduates are especially vulnerable to leaving the profession within the first two years following graduation; being thrust into the pandemic working conditions may exacerbate an exodus of these novice nurses. Interviews conducted by our team in the spring of 2020 and 2021 suggest that nurses working in hospitals did not feel prepared to face the mental, social, and physical challenges of working under pandemic conditions. The goal of this project is to create and pilot a training program that will prepare nursing students to work during this pandemic and/or other extreme healthcare crises. The program will consist of 10 training modules combining online content and in-person practice; topics may include trauma, burnout, moral distress, self-care and resiliency, working with racialized patients during COVID, and stigma. Content will be reviewed both by mental health experts, nursing students, and nurses currently working in the field to ensure that it is appropriate to the needs of nurses working under extreme healthcare crises. Both qualitative and quantitative data will be collected to determine the impact of the program on self-efficacy, resiliency, confidence, and knowledge of mental health/coping strategies. The program will also be piloted at partner sites to ensure its utility and applicability across nursing programs. The goal will be to make training materials available to other nursing programs across Canada, and eventually develop online modules for nurses who did not receive this training while in university.",2021,2023,University of Windsor,320732.1,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C19740,202111WI1,Leaving the Hospital with Nowhere to Go: The Impact of Rapid Hospital Transitions During COVID,"During the various waves of COVID-19, many patients, who were historically difficult to discharge (Alternate Level of Care patients) were rapidly moved out of hospital to make room for COVID patients. ALC patients have completed their acute care treatment but they are characterized by chronic conditions that require ongoing care. Our team conducted a quantitative study showing that ALC patients who were rapidly discharged were more likely to experience poor outcomes and less likely to get access to post hospital care (including long-term care, primary and specialist care) and were more likely to be readmitted to hospital or die, compared to ALC patients before the pandemic. While we have these data, we don't know why this happened, including what types of patients benefited from a rapid discharge and those who did not. Given that hospitals are historically over capacity it is important to understand this distinction as we move into our post COVID recovery period. Our team will conduct a qualitative study and interview patients, their family members, care providers and system decision makers across Ontario who were impacted by rapid hospital discharge so we can understand their experiences, gaps and work together to create better transitions of care for the future.",2021,2023,"Trillium Health Partners (Mississauga, ON)",184860,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19741,202111WI2,Lessening the Impact of COVID-19 on Child and Youth Mental Health,"There is growing evidence that the pandemic and measures meant to curb spread of the virus, such as school closures and mask mandates, had repercussions on the mental health of children and adolescents. However, the pandemic's impact on youth mental health remains unclear. Children are underrepresented in research, and most studies are based on self-reported symptoms of depression, anxiety, and stress. This project will determine how the pandemic affected major youth mental health problems in Quebec, including suicide attempt, drug overdose, eating disorders, and injuries due to child maltreatment. We will identify whether policies and practices such as curfews during the pandemic had an impact on these outcomes. We will also identify specific subgroups of children and adolescents that were more vulnerable during the pandemic. To carry out this work, we will analyze all hospitalizations in children and adolescents under 20 years of age in Quebec, Canada before and during the pandemic. We will study suicide attempt, drug overdose, alcohol intoxication, eating disorders, and home injuries due to maltreatment. We will assess whether pandemic control measures, socioeconomic conditions, chronic diseases, and other characteristics of children influenced the pandemic's impact on youth mental health. This project will measure the impact of COVID-19 on understudied mental health problems in children and adolescents, and will identify vulnerable groups in need of support during pandemic recovery and future public health crises. Quebec was the most severely affected province at the start of the pandemic. Quebec's experience can provide invaluable information to provinces that were less heavily affected or affected later in the pandemic. The findings will be disseminated to health authorities, policymakers, and healthcare professionals to guide priority setting and interventions for pandemic control in all of Canada.",2021,2023,Institut national de santé publique du Québec,218893.99,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19742,202107UIP,"Leveraging a Longitudinal Canadian Cohort to Study the Course of Parent-Youth Mental Health Before, During, and After the COVID-19 Pandemic","The past year has been an extraordinarily challenging time for families coping with ongoing changes and disruptions due to COVID-19. Unfortunately, stress, unpredictability, and disruptions can catalyze mental illness. Cross-sectional studies show that rates of anxiety and depression are on the rise during COVID-19, particularly in parents and youth. What is unknown is whether these rates will be maintained once COVID-19 disruptions have attenuated. In addition, there is no research showing how these increased rates correspond to health service utilization. High-quality, contemporary data on how parents and youth are independently and collectively coping with, and recovering from, the pandemic is crucial to inform the allocation of scarce mental health resources. Our study will provide this information. The All Our Families (AOF) study, a pregnancy cohort in Calgary that started in 2008 and has followed families over time, has surveyed mothers and youth (now aged 9-11 years) three times during the pandemic. We now seek to survey families in the recovery phase of COVID-19 in February of 2022 to examine the longitudinal trajectories and co-development of parent and youth depression and anxiety prior to, during, and in the aftermath of the pandemic. We aim to link cohort data to administrative mental health data to identify the patterns of diagnoses and health service utilization in the context of changing mental health symptoms. We aim to identify the patterns of risk and protective factors that have amplified and/or attenuated mental distress. This proposal provides an exceptional opportunity to identify who becomes most at risk based on both the structural determinants of health and personal/familial factors. Identification of the patterns of stability and change in mental health due to COVID-19, along with service utilization, can help inform decisions on resource allocation and prevention and intervention strategies to optimize mental health.",2021,2022,University of Calgary,118494.47,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19743,202109EG8,Linguistic and Cultural Adaptation of Web-based Partner Violence Screening and Safety Planning Applications,"One in 3 women will experience intimate partner violence (IPV) in her lifetime. COVID-19 has tripled the IPV prevalence while simultaneously shutting down in-person services creating unique challenges for women experiencing violence. Technology has been one of the few means to reach out to and support women living with IPV. While cisgender women in heterosexual relationships comprise the largest number of those experiencing IPV in Canada, rates of abuse for women can be higher and more complex in racialized and other marginalized communities due to intersectional structural stressors. Unfortunately, services and resources are disproportionally scarce to support these populations. Existing IPV app resources are predominantly in English and for use among women in heterosexual relationships. We have an opportunity to expand the availability of screening and safety planning online, to non-English speaking communities. The objective of this work is to culturally and linguistically adapt existing evidence-based screening () and safety planning ( and ) web-apps to reflect the appropriateness of IPV apps for French and Spanish speaking communities. Our community partners for this initiative have identified an urgent need for our evidence-based apps to be made available to French and Spanish speaking populations with French being an official language of Canada, and Spanish also a commonly spoken language in Canada among many cultural populations. Our apps will be iteratively reviewed, revised and tested for acceptability by identified cultural survivors and IPV service providers. Once developed, we will employ the strategies outlined through a user guide developed by our team to assist partners in implementing these apps within their service settings.",2021,2022,Unity Health Toronto,386430.87,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19744,202109EG6,Living Systematic Reviews and Knowledge Mobilization of Care Models and Management Options for Long COVID/Post COVID-19 Condition.,"Even if the pandemic ended today >20M people worldwide would still be living with the consequences of Long COVID (Post COVID-19 Condition), the patient-derived term describing long-term symptoms and sequelae of COVID-19. Long COVID hits across the lifespan, impacting quality of life and employment participation. Anticipated costs are alarming. Massive research investment is leading to the development of evidence-based care models and management options. There is an urgent need to accelerate the availability and use of this knowledge to Canadians. Our overarching goal is to support rigorous, accessible and financially sustainable health systems organization delivering evidence-based care to improve quality of life and functioning, promote safe return to work/school and optimize Long COVID recovery. Our specific aims are to: 1) Conduct two living systematic reviews of care models and management options for Long COVID and 2) Implement a knowledge mobilization hub to share real-time high-quality evidence with people living with Long COVID, clinicians, researchers, and policymakers across Canada and internationally. Long COVID communities support our team and will help us consider all aspects of equity, diversity, belonging and inclusion. We will: 1) Leverage Canada's SPOR Evidence Alliance and COVID-END knowledge synthesis infrastructure to produce ongoing, high-quality evidence supporting the provinces' health systems organization; 2) Train a sustainable and person-centred workforce to support care and recovery of people with Long COVID and advocate for rehabilitation needs in case of long-term disabilities; 3) Serve the international community, including low- and middle-income countries, by providing tailored and freely available knowledge to support people with Long COVID. 4) Identify evidence gaps in care models and management options to drive a long-term research agenda.",2021,2022,Université de Sherbrooke,179488,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Health Systems Research | Research on Capacity Strengthening,"Supportive care, processes of care and management | Post acute and long term health consequences | Health leadership and governance | Cross-cutting",2021 +C19745,202111WI2,Lonelier Than Ever: Examining the Experience of Loneliness amongst Adolescents with Chronic Pain in the Context of COVID-19: A Mixed Methods Study.,"Chronic pain effects 1 in 5 teens in Canada. Previous studies found that teens with chronic pain are lonelier than teens without pain and that their loneliness was linked to depressed mood, anxiety, and worse scores on questionnaires about self-esteem, before the COVID-19 pandemic. However, these studies did not describe the type of loneliness teens with chronic pain experienced. For example, one can have a best friend but be lonely for a larger circle of friends, or one can feel that they don't belong to a wider community like their school and therefore suffer loneliness. Interventions to improve loneliness for teens with chronic pain depends on why they are lonely. Understanding more about loneliness, and ways to mitigate it, is important because loneliness has been found to be a risk factor for worse mental and physical health outcomes for children, teens, and adults. In fact, loneliness is as important a risk factor for health as smoking. Moreover, loneliness could have even worse health outcomes for those who already have mental or physical health problems like chronic pain. Also, the longer one is lonely the worse their physical or mental health and our previous research showed that teens with chronic pain remain lonelier than those without pain over a calendar year. During COVID-19, public health restrictions, such as online schooling, social gathering restrictions, and not being able to socialize with people outside of one's home has resulted in higher rates of loneliness in teens without pain but we don't know how COVID-19 has impacted loneliness in teens with chronic pain. Our study will help us understand how the COVID-19 pandemic has impacted loneliness in this specific population, assessing the type of relationships or situations in which they experience loneliness, and how their loneliness has impacted their physical and mental health. Findings from this study will help us understand ways to help teens with chronic pain decrease their loneliness.",2021,2023,University of Ottawa,188988.54,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19746,202111WI2,"Loneliness Among Older Adults in COVID-19: A Living Systematic Review of Changes in Loneliness from Pre-COVID-19, Association with Mental Health Outcomes, and Effects of Interventions","There will be serious loneliness and mental health implications from COVID-19 that extend beyond the pandemic for many people, especially older adults. Addressing these needs requires understanding their nature and extent and evidence on effectiveness of interventions that may be rapidly employed to prevent or address loneliness and mental health concerns. Studies from COVID-19 are published rapidly, but many are of dubious quality. Thus, curation of this growing evidence base is urgently needed to provide practitioners and policy makers with clear, coherent evidence synthesis. Living systematic reviews are systematic reviews that are continually updated and provide ongoing access to results via online publication. They are logistically challenging, but provide value beyond conventional systematic reviews in situations where (1) important decisions need to be made; (2) uncertainty in existing evidence poses a barrier to decision-making; and (3) new evidence is emerging rapidly. Such a review is urgently needed to guide mental health care during and following COVID-19. Our research team has expertise in high-impact evidence synthesis research (). Our protocol has been made public on the Open Science Framework (). We have already sorted through over 190,000 citations from 10 databases, including two Chinese-language databases, reviewed over 69,000 unique citations, and identified over 260 eligible studies, including studies on older adults. We have published initial evidence online from general populations (). We are working closely with Canadian government personnel to inform mental health strategy for older adults. Important evidence will be published in the months to come. It is crucial to maintain funding for this important project to incorporate the higher quality evidence that is beginning to be made available.",2021,2023,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,291507.63,Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19747,202107UIP,"Love Together, Parent Together (L2P2): A pilot RCT of a brief couples' intervention for parents of young children amid the COVID-19 pandemic","The COVID-19 pandemic poses a significant threat to the relationships of couples with young children, which has the potential to infiltrate family systems and negatively impact all family members. There is a pressing need for psychosocial programs for couples with young children to guard against relationship deterioration. The current proposal is for a pilot RCT of a brief, fully-online, couples-focused intervention for parents of young children. This will establish feasibility of a future, main RCT and also provide preliminary evidence for its positive benefits to couples and their families. The Love Together, Parent Together (L2P2) program is adapted from the 'Marriage Hack', a previously validated intervention that promotes conflict reappraisal in couples. We have shortened the duration of the program (from one year to four weeks) and will examine its viability in couples with young children during (and following) the pandemic. The design is a two-arm randomised trial (treatment vs. waitlist control), with pre-, 1-week post-, and 3-month follow-up assessments. We will include 120 couples with children under 6-years-old. The intervention involves three 7-minute writing sessions over four weeks, wherein couples are encouraged to reappraise a recent disagreement they had with their romantic partner by taking the perspective of a neutral third party. It is theory-driven, designed to target common negative cycles observed in couples. Primary feasibility outcomes will assess recruitment, eligibility criteria, sample diversity, randomization, retention, and intervention acceptability. Secondary clinical outcomes include an examination of group differences in couple (relationship quality, conflict-related negativity) and family outcomes (parent-child relations, parent mental health, child emotional and behavioural problems). We intend to provide evidence for the feasibility and preliminary effectiveness of the L2P2 program, which may be scalable at the population level.",2021,2022,York University,59951.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19748,202112FO1,Making visible the impacts of the COVID-19 pandemic on pregnant Indigenous people in Ontario who experience mandatory evacuation for birth: A qualitative Indigenous feminist research health analysis,"Canada is in a maternity care crisis as a result of hospital maternity care closures, decreasing numbers of physicians delivering babies, and the centralization of maternity care services in large, usually southern, tertiary hospitals. In fact, from December 10, 2021 to February 21, 2022, the only maternity care unit in Yellowknife is being closed due to staffing challenges. The maternity care crisis is not being meaningfully addressed anywhere in Canada, even before the COVID-19 pandemic. Our research team is dedicated undertaking research that contributes to (re)building a national maternity care program and have focused on how maternity care is provided to pregnant Indigenous Peoples in Ontario. Indigenous Peoples have the highest birth rate in Canada and Ontario has the highest numbers of Indigenous Peoples, making this an excellent jurisdiction to examine. Unfortunately, all of the level 3+ maternity hospitals in Ontario are located in southern, urban areas that are very close to the Canada-USA border. Our research contributions to advancing health care, policy, programming, and health workforce needs begins with understanding of the comprehensive, gender-inclusive sexual and reproductive health needs in Ontario begins with two research goals: 1) to describe the practices of maternity care providers when caring for First Nations patients evacuated out of their community to give birth in an Ontario hospital during the COVID-19 pandemic; and 2) to describe the maternity care experiences of Indigenous Peoples who live on or have lived on reserves and have been evacuated for maternity care services in Ontario during the COVID-19 pandemic.",2021,2022,Queen's University,196311.05,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2021 +C19749,202109ER5,mamawohkamatowin: working together to understand the house and COVID-19 in a Saskatchewan First Nation Community,"Aim: This project aims to increase health and well-being by considering how the house impacts COVID-19 on Sturgeon Lake First Nation (SLFN). Research Questions: ((1) In what ways does the house impact COVID-19? (2) In what ways does the house impact the management of COVID-19? (3) Explore SLFN's response to COVID-19 isolation and vaccines. Methods: This research builds on a decade long health research relationship between SLFN and researchers. This team recently completed a co-created research process in which the findings revealed significant relationships between the house and respiratory health on SLFN. House factors were important to health outcomes. Having visible mold and a smell of mold in the house was correlated with both treatment and hospitalization for most respiratory health outcomes. Given that the house is important to respiratory health outcomes understanding the role of the house in COVID-19 in SLFN is an important question of the community. Sturgeon Lake Health Centre has collated data on all CoVID-19 cases in their community including close contact tracing and transmission, and residence for each case. This project will assess if the same houses that are impacted by house factors in our respiratory health survey are more impacted by CoVID-19? These findings will be built on with qualitative methods to further understand how the house impacts isolation and vaccine. The findings will be returned to the community, in ways that are meaningful to the community. Discussions of the findings and strategies for ways and means forward will be co-created with the community, While the results will be beneficial to SLFN policy and processes, the knowledge gained will likely resonate with other First Nation communities so that they are able to co-create similar programs based on their strengths and response to COVID-19. Outcome: Understand and build a strong effective community response to COVID-19.",2021,2022,University of Saskatchewan,215207.85,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Community engagement,2021 +C19750,202109EG3,MARCO:POLO Marginalization & COVID-19: Promoting Opportunities for Learning & Outreach,"Many Toronto organizations rapidly introduced programs and innovations to support people experiencing marginalization during the COVID-19 pandemic. The MARCO (Marginalization and COVID-19) study, a collaboration between academic and community investigators, is using program evaluation methods to evaluate such community-led interventions. Our focus in MARCO was on using descriptive and deductive analyses to identify findings with the greatest potential for immediate impact, with a focus on service delivery that is more equitable and client-centered. However, the large amount of data that we collected offers additional opportunities. MARCO:POLO is an extension study to MARCO; our aim is to generate a deeper understanding of marginalization in health by addressing questions across evaluations, with a specific focus on systems and policy-oriented frameworks and questions addressing innovation and racism. Our approach is based on the understanding that this level of analyses is necessary for driving social change.",2021,2022,Unity Health Toronto,247905.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +C19751,202107UIP,"Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN): Youth mental health mental in the COVID pandemic","The COVID-19 pandemic has resulted 1.4 million cases have been confirmed with 26,192 deaths in Canada, with Quebec and Ontario being hit the hardest. Preliminary analyses of a recent survey from four countries indicate that 53.2% of Canadian adults met criteria for PTSD. However, studies into the effects of the pandemic on child and adolescent mental health are limited even though it is believed that children and adolescents are at risk for mental health problems. While public health protocols have been effective in 'flattening the curve', social distancing and modifications enforced in the education system (hybrid teaching, full on-line teaching) have been extremely difficult for children and adolescents. Why certain youth develop COVID-related mental health problems while other appear resilient in the face of stress is not fully understood. Evidence points to unique aspects of gestation, the child's biology, and the quality of the early environment. The Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project is a prenatal cohort specifically designed to examine such questions and has found that the combination of early maternal adversity, genetics, and the early environment modify the risk for insecure attachment, negative temperament, childhood psychopathology, and the ability to remain hopeful and motivated in face of an adversity task (resilience). The main goal of the present study will be to determine how child, parental and environmental factors explain COVID-related stress and whether this stress moderates/mediates known relationships between maternal adversity and later psychopathology or resiliency in 8 to 18-year-olds. Specifically, we ask: i) How does COVID-related maternal and/or child stress combined with perinatal adversity and child genetics to predict current mental health functioning in youths; ii) Are there environmental factors (parental stress level) and child factors (early measures of resilience) which mediate this association?",2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,118479.46,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19752,202109EG9,Measuring salivary antibodies (Abs) in COVID-19 vaccinated children,"We expect approval of a COVID-19 vaccine for children between the ages of 5-12. With this in mind, we seek to build capacity to evaluate the antibody response of children in this age bracket to the COVID-19 vaccine and understand how the antibody response relates to breakthrough infections. Our clinician partners from the COVID-19 Immune Task Force (CITF) pediatric network will collect saliva samples from children who are administered vaccines. We will use an Enzyme-linked immunoassay approach to measure IgG, IgA, and secretory IgA antibodies. This result will allow us to measure antibody levels and correlate these levels with breakthrough infections. In parallel, we will develop a multiplex serological test using quantum dot/smartphone barcoding technology. This device is portable and can detect multiple antibodies simultaneously. The results can be wirelessly connected to a doctor's office or public health laboratory to monitor immunity. Our antibody studies are critical for decision-making (e.g., booster shots), while our device could be useful for tracking immunity in the current and future pandemics.",2021,2022,University of Toronto,382781.86,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C19753,202108VCF,Measuring vaccine hesitancy and examining reasons behind vaccination choices for the COVID-19 vaccines in patients followed in primary care clinics,"The discovery of vaccines has been essential in the improvement of health and life expectancy. However, the decision of whether or not to get a vaccine is with the patients and many factors can make people hesitate. While most of the population is vaccinated already, parts of the population remain hesitant. It is now time to verify what can be done in primary care settings to help patients increase trust in COVID-19 vaccine, and work with them to increase that trust. We propose a project with three objectives: 1) To measure vaccination coverage and the importance of different factors influencing the decisions for COVID-19 and flu vaccination in adults followed in family medicine clinics in Quebec; 2) To identify factors associated with non-vaccination and incomplete COVID-19 vaccination, in order to develop interventions to increase vaccine confidence and acceptance; and 3) To co-design interventions to increase COVID-19 vaccine confidence and acceptance for and with specific subgroups identified in Aims 1 and 2, with a patient and community engagement approach. To do this, we will recruit 1185 adult patients followed in primary care clinics. Data will be gathered through a questionnaire completed with a research assistant and a chart review. We will then use this information to identify subgroups with more hesitancy to get the COVID-19 vaccines and will conduct workshops to co-design interventions to increase trust in the vaccines with these communities. These workshops will involve collaboration and discussions between doctors, patients, public health professionals and other community partners to co-design recommendations to improve healthcare as it relates to COVID-19 vaccines, in an adapted manner responding to the needs of specific communities. We offer a collaborative approach that is aligned with primary care approaches, and more likely to provide long term and sustainable benefit in COVID-19 vaccination coverage and beyond.",2021,2023,Research Institute of the McGill University Health Centre,157921,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19754,202111WI1,"Mental health and long COVID: Experiences, interventions, and resilience building","Background. While COVID-19 infection generally results in a mild to moderate short-term illness, some people experience symptoms for months after infection; this is known as 'long COVID.' It is important to understand long COVID experiences, including mental health impacts, and to identify promising psychosocial interventions for this population. Objectives. 1) Understand what is known about psychosocial interventions for long COVID; 2) Understand how patients are experiencing long COVID, particularly impacts on their mental health; 3) explore whether a psychosocial intervention, the Optimal Health Program, might be appropriate to support self-management, mental health and resiliency for Canadians with long COVID. Method. We will conduct a systematic review to understand what the scientific literature says about psychosocial interventions for long COVID, and we will update the review one year later. We will also conduct focus groups with 1) individuals with long COVID and associated mental health challenges, including young adults, mid-age adults, and older adults, and 2) physicians who treat such patients. Focus groups will examine how participants have experienced long COVID, how it has impacted self-care and self-management activities that support positive mental health and resiliency, barriers to self-care, impacts on substance use, and novel skills or resilience factors that have emerged. We will further facilitate discussion on the Optimal Health Program as a possibly promising intervention for self-management, positive mental health and resilience in long COVID. We will engage patient partners in all phases of the project. Impact. This study will help understand the experiences and needs of Canadians with long COVID and associated mental health challenges and identify interventions. It will thereby identify concrete solutions to helping vulnerable Canadians recover from the long-term impacts of COVID-19 infection.",2021,2023,Centre for Addiction and Mental Health (Toronto),161957.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease pathogenesis | Post acute and long term health consequences | Community engagement | Indirect health impacts,2021 +C19755,202107UIP,Mental Health of Black Youth after the COVID-19 Pandemic,"Coronavirus disease 2019 (COVID-19) has killed many people in Canada and around the world. To stop the spread of the disease, the Government of Canada implemented several preventative measures, including physical distancing. While these measures helped contain the spread of the disease months after its outbreak, the pandemic will have a long-lasting effect on mental health of the youth. The pandemic poses a ""double whammy"" for Black youth, as they are at increased risk of mental health problems and Black Canadians are at an increased risk of contracting and dying from COVID-19. However, race-based data on the mental health of Black youth in Canada during or after the COVID-19 pandemic are not readily available. Our proposed work seeks to examine the mental health of Black youth after the COVID-19 pandemic and offer interventions to address mental health risks in this demographic. This project will be conducted in two phases. Phase 1 will involve up to 30 interviews with Black youths to determine how the pandemic has affected their mental health. Phase 2 will involve a survey of Black youths in Canada. We will develop documentary videos, policy briefs, and webinars based on our findings. Our research will provide much-needed data on reducing the mental health impact of the COVID-19 pandemic on Black youth. Our team has complementary expertise in Black people's health, youth mental health, quantitative methods, qualitative, and participatory action research. Members of the team and partners are well engaged with the Black community.",2021,2022,University of Alberta,117905.92,Human Populations,Black,Adolescent (13 years to 17 years),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19756,202107UIP,Mental health of children and youth amid COVID-19 in Quebec,"COVID-19 has profoundly impacted the lives of children, youth and families. There is growing evidence that the pandemic and measures meant to curb spread of the virus, such as school closures and mask mandates, had important repercussions on the mental health of children and adolescents. However, the breadth of the pandemic's impact on youth mental health is still unclear. This project will determine how the pandemic affected youth mental health in Quebec, including suicide attempt, drug overdose, eating disorders, and injuries due to child maltreatment. The project will identify children and adolescents at greater risk of mental health problems during the pandemic. We will use a large dataset containing all hospitalizations in Quebec, Canada. We will extract data on boys and girls under 20 years of age before and during the pandemic (2006-2019 vs 2020-2021). We will study hospitalizations for suicide attempt, drug overdose, alcohol intoxication, eating disorders, and home injuries due to maltreatment. We will assess whether socioeconomic status, mental health conditions before the pandemic, chronic diseases, and other factors influenced the pandemic's impact on youth mental health. We will measure time trends in hospital admissions for mental health conditions and maltreatment-related injuries among boys and girls before and during COVID-19, including the impact of pandemic control measures. We will also follow children over time to identify the social, demographic, and clinical characteristics that influenced the risk of hospitalization for mental health problems and injuries during the pandemic. This project will determine how COVID-19 affected the mental health of children and adolescents in Quebec, and will identify vulnerable groups in greater need of support during pandemic recovery and future public health crises.",2021,2022,Institut national de santé publique du Québec,118500,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Drug users | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19757,202111WI1,Mitigating the Long-Term Impact of the COVID-19 Pandemic on Colorectal Cancer Care and Control in Alberta: Developing a Live Colorectal Cancer Activity Dashboard.,"The COVID-19 pandemic introduced a multitude of challenges to the cancer care delivery system. Colorectal cancer (CRC) prevention and diagnostic tests such as fecal immunochemical tests (FIT) and colonoscopies declined dramatically during the first wave of the pandemic. Similarly, CRC-related treatments were postponed, delayed, or dramatically altered. As the COVID-19 containment measures are extended to combat the rapid unfolding of new variants, it is likely that the quality and the quantity of cancer care and control will be impacted for years to come. The pandemic has illuminated a considerable limitation in cancer control - at present we do not have timely or near real-time access to health data to even quantify the impact on systems. These data gaps are a challenge for the health system, policymakers, and health professionals to raise the alarm of where patients and procedures are being missed. Without this information the delivery of evidence-based cancer prevention and care is not feasible. The proposed research aims to develop a dashboard that displays interactive, near real-time CRC care and control data in the province of Alberta. First, the dashboard will be utilized to monitor monthly volumes of completed or overdue CRC screening, diagnostic, and surgical procedures. Second, we will estimate the backlog volumes of CRC activity procedures by region in Alberta. Third, we will examine monthly CRC activity backlog volumes by measures of socioeconomic status, ethnicity, and immigration status to see how pandemic-related delays have differentially impacted the population. With these data we will be able to develop targeted community engagement strategies to help increase participation in population-based CRC screening as well as mitigate diagnostic and surgical backlogs. This dashboard will support decision-makers, the public health community and healthcare providers in planning and monitoring population-based CRC care and control efforts.",2021,2023,University of Calgary,355500,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19758,202002OV8,Mitigation strategies against the public transmission of airborne COVID-19 in high occupancy structures: a program of research to develop optimized mechanical ventilation systems,"This research program brings together experts in Engineering and Medical Sciences to develop Non-Pharmaceutical Interventions (NPI) related to mechanical ventilation systems in buildings. These settings have high concentrations of humans in enclosed spaces where the spread of airborne infections can have rapid, extensive, and detrimental consequences in terms of morbidity, mortality, and ultimately productivity and costs. This research program targets a key mechanism of COVID-19 transmission, that is, transport of the virus through heating, ventilation, and air conditioning (HVAC) systems with subsequent inhalation by other people. Currently, it is not clear how human-generated bioaerosols affect airborne virus transmission and how HVAC systems should be optimally designed and operated to reduce the risk of transmission. This research program will include: 1) a thorough review of building science literature related to airborne virus transmission; 2) a policy directive for governing organizations who inform owners and operators of ventilation systems and building code bodies; 3) an inventory and assessment of over 100 buildings with diverse ventilation systems; and 4) an inventory and assessment procedure and protocol for other buildings. This research directly aligns with the objectives of the funding opportunity, in particular, to mitigate the rapid spread of COVID-19 and its potential negative consequences. Based on the research results, we will develop evidence-based guidance and policy recommendations to inform the design/re-design of buildings. This work has the potential for widespread impacts in terms of establishing policy and procedures that can be applied locally, nationally and internationally. Further, this research will inform the immediate response to the COVID-19 outbreak while having a broader impact in terms of the spread of other airborne illnesses/contagions and future outbreaks.",2020,2022,University of Alberta,266400,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2020 +C19759,202002OV3,Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),"SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",2020,2022,Unity Health Toronto,750000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Western Pacific,Western Pacific,,,,China,China,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19760,202111WI1,Moral distress in critical and primary care providers from the COVID-19 pandemic: A cross-provincial mixed-methods case study,"News reports have highlighted that hospital-based clinicians, including physicians, nurses, and social workers are leaving their professions, catalyzed by COVID-19 circumstances which resemble moral distress and moral injury. ""Moral distress"" is the response of a person who feels morally constrained by institutional or other constraints, and ""moral injury"" is when one feels morally betrayed by those in power during high stakes situations. Health care providers working in critical care and family medicine have expressed feeling more anxious and exhausted, and having negative mental health outcomes, including depression, burnout, apathy, and post-traumatic stress disorder, all of which resemble moral distress and moral injury. Critical care and family medicine were chosen for this study as their distress manifests in differing ways; these environments vary in their approaches to and goals of their clinical tasks and care provision with respect to practice settings, acuity, care continuity and relationships. This project aims to explore the effects of moral distress on health care providers in critical care and family medicine environments through the pandemic in two provinces with high infection rates (Ontario and Alberta). To do this, a case study methodology will be employed, in which quantitative data will be collected to measure rates of attrition and burnout, and qualitative methods will be employed to understand providers' experiences during the pandemic. The objective of this is to understand the contexts that shape their moral distress, in order to provide policy and institutional suggestions for stopping attrition and burnout.",2021,2023,McMaster University,196214.67,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C19761,202002OV3,Neutralizing Antibodies as SARS-CoV-2 Therapeutics,"Three highly virulent coronaviruses - SARS-CoV, MERS-CoV and SARS-CoV-2 - have crossed species barriers to infect humans since 2003. SARS-CoV-2 is responsible for COVID-19, a disease that arose in Wuhan China in December of 2019. The virus has infected over 64,000 people and caused 1380 deaths and the World Health Organization has declared it a public health emergency of international concern. Although drastic measures are being taken to contain SARS-CoV-2, there is an urgent need for new therapeutics to combat this virus and reduce its spread. In this work we will develop therapeutics based on human antibodies that can be used in the treatment of COVID-19.",2020,2022,University of Toronto,401488.5,Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19762,202002OV3,Neutralizing human-derived single-chain antibodies against SARS-CoV-2,"SARS-CoV-2 is a virus that has caused an epidemic of human respiratory disease (COVID-19). It first emerged from the city of Wuhan in Hubei in December 2019 and has since spread widely in China and to more than 24 counties globally. The virus has been declared as a deadly global threat, and accelerated international efforts have been engaged to control the virus. A total of 1,524 deaths been confirmed as of 15th February 2020 (WHO). As a result of the rapid transmission internationally, a global call to control the spread of the virus in affected and non-affected areas has been implemented. Currently, there is no effective treatment or vaccine to control the virus. Symptoms of the infection include respiratory symptoms, fever, cough, and shortness of breath. In more severe cases, the infection can cause respiratory failure, severe acute respiratory syndrome, kidney failure, and death. The objectives of this application are 1) to develop antibodies that will block the entrance of the virus into the cells, and to test the efficacy of these antibodies in mice.",2020,2022,University of British Columbia,296700,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19763,202107UIP,"Nothing without us: Towards inclusive, equitable policy strategies for youth with disabilities and their families post-COVID19","Persons with disabilities and their caregivers are an at-risk population in the COVID-19 pandemic who's mental health has been disproportionately impacted by the policy measures adopted in response. Given the increased risk for this vulnerable population during the pandemic and existing higher rates of mental health concerns, policy and services that are not designed to meet the needs of people with disabilities and their families can add to or create mental health concerns. Addressing these risks in the spirit of ""Nothing Without Us"" and the Accessible Canada Act, and in recognition of Canada's domestic and international human rights obligations is critical. Unfortunately, there is inadequate data collection and insufficient policy planning and response for people with disabilities. The goal of this project is to identify policy responses established during the COVID-19 outbreak in Canada and internationally that promote resilience and address mental health challenges and needs of youth with disabilities and their families. To achieve this we will: 1) Identify and analyze COVID-19 policy priorities for recovery for a disability inclusive approach and promote health/resilience in youth and families in provincial/territorial and federal jurisdictions and alignment with United Nations Convention on the Rights of Persons with Disabilities (UN CRPD) and the WHO's recovery recommendations; 2) Prioritize equitable COVID-19 policy priorities for recovery with youth and families based on identified needs and experiences with COVID-19 provincial/territorial policies of youth with disabilities and their families in every Canadian province and territory; 3) Co-design and mobilize COVID-19 policy priorities for recovery recommendations that are inclusive, equitable, and evidence-informed with stakeholders to meet health needs, mitigate harms, and promote well-being for youth with disabilities and their families for systems-level policy impacts across Canada",2021,2022,University of Calgary,118460.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19764,202107UIP,NOURISH-US: patieNt-Oriented research to Understand and addRess Inequities of food accesS and insecurity amongst Households managing food allergy - a Unique intervention Study,"As unemployment rates have doubled since the start of the COVID-19 pandemic, many families are at risk for food insecurity. Compared to families with no food restrictions, families whose children have food allergy are saddled with higher food costs, prior to, and during the pandemic. Yet, existing food banks in Manitoba do not adequately support these families with food allergy, given the increased demand for food bank services by the non-allergic families and thus, the inability of food banks to support families with food allergy. Our patient-oriented food allergy research project aims to understand and mitigate the inequities of food access and insecurity. Using data on food insecurity and food allergy, collected immediately before and during the pandemic, we will establish national rates of food insecurity, and food costs during the pandemic, and compare these to pre-pandemic levels, amongst households managing food allergy. Then, we will conduct an allergy-friendly food delivery intervention amongst economically-disadvantaged households managing cow's milk allergy in Winnipeg. Data collected at the start, and the end of the trial will help us understand how to mitigate the impact of food allergy and food insecurity, including how mental health is impacted when subsidies are in place. We will share our findings via scientific conferences and publications. Our team of investigators has internationally recognized expertise in pediatric food allergy, mental health and policy. We will work with collaborators with expertise in philanthropy and health economics to use the findings from this one-year study to ensure sustainability of the project. Our well-defined project and long-term vision are critical, as the impacts of the COVID-19 pandemic will take years to mitigate.",2021,2022,University of Manitoba,86900,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C19765,202107UIP,Operationalizing 'best practices' that promote healthy lifestyles and mental health to mitigate the impact of the COVID-19 pandemic on elementary school children in disadvantaged communities,"Measures implemented to slow the spread of COVID-19 created a lot of hardship for school-aged children. These measures included closures of schools and orders to stay home for many weeks. Considerable concerns have emerged about the impact of these measures on children's health and wellbeing, which may have long-term consequences. This research builds on a 13-year partnership with a program called APPLE Schools, which delivers a successful intervention to promote healthy living and mental health to kids from disadvantaged settings and currently operates in 74 elementary schools. APPLE Schools developed innovative easy-to-implement practices to support schools during COVID-19. These practices were designed to promote student healthy living and mental health to ensure health remained a priority while school communities were faced with challenges. In partnership with APPLE Schools, we collected data on students' lifestyle behaviours (diet, physical activity, screen time, sleep) and mental health (mood, feelings) in 20 schools during COVID-19. We also gathered data on COVID-19 lived experiences through interviews with students and their families, and data on school supports during COVID-19 reported by principals. We have also generated an inventory of health promotion practices delivered in APPLE Schools during COVID-19. We now propose research to identify and document the most successful practices in APPLE Schools during COVID-19, develop an online Best Practices Toolkit, and promote dissemination and uptake of the toolkit in all APPLE Schools and other elementary schools across Alberta. We will emphasize promotion of the toolkit in schools in socioeconomically disadvantaged settings to accelerate pandemic recovery and to alleviate health inequalities. The knowledge from this study will yield practical, actionable and scalable solutions that will enhance student supports to help mitigate the impact of the pandemic on children's mental health and lifestyle behaviours.",2021,2022,Unity Health Toronto,118498.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Indirect health impacts",2021 +C19766,202005VR3,"Optimizing polar, small inhibitors of a viral cysteine protease to identify a lead for an oral COVID-19 treatment","The COVID-19 pandemic has caused incredible social, personal and economic upheaval and as of early May 2020 killed 275 000 people world-wide and, tragically, is projected to kill millions more. COVID-19 is caused by the SARS-CoV2 (SARS2) virus, which is a coronavirus closely related to SARS. These viruses infect cells and using the host's enzymes and virally encoded proteins create copies of themselves. These viral proteins are different than the host ones and are key targets to stop the viral replication. One such protein for SARS2, nicknamed 3CLP, is key to liberating the viral proteins in order to enable viral replication. Last month compounds we tested strongly inhibited the SARS2 3CLP and were able to inhibit SARS2 replication in a cell-based assay. This proposal is to design and make modifications of those compounds to better inhibit SARS2 and also optimize drug-like properties to discover a Lead compound for the ultimate development of an oral drug to treat COVID-19.",2020,2021,University of Alberta,438921,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19767,202109EG7,"Pandemic Planning for Primary Care: Developing an Integrated Response Framework for Family Physicians, Nurses, and Pharmacists","Primary care providers play an important role in pandemic response and recovery. Primary care nurses (PC-N; i.e. Nurse Practitioners, Registered Nurses and Licensed/Registered Practical Nurses) have been deployed from their routine responsibilities to take on pandemic-related roles, particularly in initiatives to care for marginalized populations. Building on our existing studies on family physicians and community-based pharmacists during COVID19, this project consists of two linked studies examining primary care pandemic responses across four regions in Canada: Newfoundland and Labrador, Nova Scotia, Ontario, and British Columbia. First, in the PC-N Study, we will combine a document analysis with qualitative interviews with PC-N to describe PC-N pandemic roles and the facilitators and barriers to these roles; and compare and contrast these findings across the four regions. Second, in the Framework Development Study, we will develop program logic models for primary care pandemic plans that integrate the findings for PC-N, family physicians and community-based pharmacists. The project addresses theme #6 (Health Care Systems and Services) and will generate high-quality evidence to improve the management of COVID-19 and enhance future pandemic preparedness. Individuals with complex chronic disease, mental health and substance-related health issues, and the elderly are particularly reliant on primary care to maintain their health during and following a pandemic. Primary care providers have played a central role in programs designed to improve access to care for marginalized populations. Innovations that emerged during the COVID19 pandemic to address marginalized populations need to be incorporated into pandemic plans to ensure that promising practices and lessons learned during the COVID19 pandemic are captured and used in the response to future pandemics.",2021,2022,Western University,394696.64,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2021 +C19768,202202PHP,Pediatric Outcomes imProvement through COordination of Research Networks (POPCORN),"Severe COVID-19 is rare in children but given the huge number of infected children, COVID-19 is a major cause of pediatric disease. In addition, some COVID-19-related issues are worse in children, such as the multi system inflammatory syndrome of children (MIS-C), with its heart inflammation (myocarditis). Indirect effects like social, mental health and educational problems due to cancelled school and extracurricular activities also need to be evaluated. Although many groups are doing excellent research on pediatric COVID-19 in Canada, they each work on a separate aspect of COVID-19 and have not had an easy way to share information with each other. For example, researchers in pediatric emergency rooms and intensive care units may have enrolled the same child, without even knowing it. To see ""the big picture"", we need to link all of the information and be able to follow a child from the beginning to end of their illness. Although the indirect effects of COVID-19 have likely harmed more children than the infection itself, this area has not been given as much attention. For all these reasons, we will integrate and strengthen the current research on pediatric COVID-19 across Canada. By doing so, we will also prepare Canada to be able to study other pandemics or diseases in children, rapidly and efficiently, in the future. This initiative is called POPCORN (Pediatric Outcome imProvement through COordination of Research Networks). POPCORN's main goal is to establish a unified research structure that is able to comprehensively answer important child health questions, starting with COVID-19. POPCORN is made up of the leaders of all the large pediatric COVID-19 research groups, who will be supported by a coordinating centre along with teams of experts on how to collect, share, and analyse data across studies, and hospitals. As such, POPCORN will be invaluable for protecting Canadian children against COVID-19, as well as whatever health problems will emerge in the future.",2022,2024,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",5159000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Epidemiological studies | Secondary impacts of disease, response & control measures",,2022 +C19769,202005VR3,Peptide macrocycle decoys against COVID-19 viral spike protein,"Peptides are potent, easy-to-synthesize, and synthetically accessible molecules that can specifically interact with pathogens. Peptides have been used to treat diabetes, neuropathic pain, cancer, and HIV. As chemists we have very recently invented news ways to make peptides both more potent as well as fluorescent in order to see where they go and how they act. We are poised to interface our technology with molecular modelling to synthesize peptides that will intercept the virus before it can enter a cell. These peptides can be injected or nasally delivered for therapy and can be used prior to vaccine development or in cases where certain patients cannot be vaccinated.",2020,2021,University of British Columbia,125292,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19770,202107UIP,Perinatal psychological distress during the COVID-19 pandemic and the effects on infant brain development during the first year of life,"The COVID-19 pandemic has increased anxiety and depression in pregnant individuals, but how will this affect their developing child? Maternal stress during pregnancy and the first year of a child's life can impact children's behaviour and mental health for many years. This likely occurs because of changes to brain development, but these mechanisms are not well understood. Through our national Pregnancy during the COVID-19 Pandemic Study, we have collected online survey data from pregnant individuals during pregnancy and postpartum, including detailed mental health measures. Here, we will brain scan infants born to a subset of these mothers in Calgary, Alberta and London, Ontario. By scanning infants at 3-months and 12-months of age, we can understand how brain development is affected by maternal anxiety and depression. We will also examine if social support, sleep and physical exercise can offset these effects. Once we understand how maternal distress affects the developing brain, we can use this information to help identify the infants who are most affected by maternal distress and importantly, which children may be at risk of developing behavioural or mental health problems. This knowledge can be used immediately to help mitigate the potential prolonged effects of maternal distress during the pandemic by informing families and health care providers who may benefit from early interventions.",2021,2022,University of Calgary,118500,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19771,202005VR2,Point of Care Heart-Lung Imaging for Patients Presenting with COVID-19 Symptoms: Artificial Intelligence Precision Modeling for Prediction of Outcomes,"point of care ultrasound (POCUS)] when patients first enter the hospital, by any physician with remote support from POCUS experts. In this study, we will test if adding heart and lung ultrasound images to existing clinical and laboratory tests can improve the accuracy and speed of COVID-19 diagnosis. A total of 16 hospitals across British Columbia and Ontario will participate in this study, and we will analyze this large data set using artificial intelligence (AI). Our team has already developed a platform to share ultrasound data and applied AI to study other heart diseases, so we are ready to rapidly apply this approach to COVID-19. If POCUS is effective it would allow earlier treatment and isolation of positive cases, reducing exposure of frontline health care workers and the public to the virus, improving both patient care and the distribution of health resources like personal protective equipment, intensive care beds and ventilators. Because POCUS-based COVID-19 diagnosis can be performed remotely it could also be applied in long term care facilities and in rural areas.",2020,2021,University of British Columbia,195244.5,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19772,202107UIP,Power over Pain Portal: A stepped-care virtual solution to deliver early intervention to Canadian youth with chronic pain,"The COVID-19 pandemic is presenting one of the greatest threats to youth mental health seen in generations. Pain is one of the most common symptoms of extreme stress in youth. Without treatment, this acute pain will become chronic (CP; pain lasting >3 months), a problem already affecting 1 in 5 Canadian youth. CP in childhood can trigger a wave of mental health issues that carry forward into adulthood. In 2019, our team revealed that ""poor access to pain care"" is a priority for youth with CP and their families. Unfortunately, COVID-19 has only made access more difficult. In 2020, our team created an online ""stepped care"" program called the Power over Pain Portal. Stepped care is a promising way to improve access to CP care. Stepped care tailors care based on a person's symptom severity. Like a ladder, a person may start with one type of care and then ""step up"" or ""step down"" to more or less intense care depending on need. Over the past year, we worked with hundreds of youth and healthcare professionals from across Canada to understand how the pandemic has affected pain and mental health. We also summarized all online pain management programs for youth to find the best resources to embed into the Portal. Together with a diverse group of youth, we have now co-designed the online Portal. The next step (focus of new grant) is to pilot-test the Portal with youth to ensure it can be implemented effectively and will be clinically beneficial. We will recruit 100 youth with CP to use the Portal for 2 months and see how they interact with the features and if it helps to improve their pain and mental health. We will include a mixture of youth who represent different ages, sexes, genders, sexual orientations, races, dwellings, and school/employment status. This study is important because it will allow our team to understand how the Portal works in the real world before wide public release to support all Canadian youth with CP with accessible, evidence-based pain care.",2021,2022,Hospital for Sick Children (Toronto),118499.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19773,202203MM1,Precision Decisions in MIS-C: Towards improving outcomes in children with COVID-19,"COVID-19 can cause a life-threatening Multisystem Inflammatory Syndrome in Children (MIS-C) typically weeks after a mild or even asymptomatic infection. Each wave of COVID-19 cases is closely followed by a wave of previously healthy children presenting to hospital in shock and heart failure due to uncontrolled inflammation. The new syndrome closely resembles Kawasaki Disease (KD). KD is the result of an infection, which triggers an over active immune system resulting in fever and inflammation of blood vessels, most importantly the coronary arteries. Similar to KD, one in four children with MIS-C develops coronary artery inflammation. It is critical to enable health care teams to rapidly recognize MIS-C, identify high risk children and control the life-threatening inflammation before it damages the child's heart. Our team has studied and dissected the reasons responsible for inflammation leading to shock and hyperinflammation in KD and have identified key biomarkers and targets for treatment. These have been rapidly translated to the bedside resulting in new medications and improved outcomes. These lessons are immediately transferrable to MIS-C, providing the evidence to guide development of effective therapeutic approaches. Our team includes doctors, scientists, and families working together to tackle this serious disease. We will use machine learning and artificial intelligence to analyze biologic and clinical data to rapidly diagnose MIS-C and predict which child will develop severe disease. We've successfully done this before in other diseases. We already have a strong and deeply committed Canada-wide team, expertise and infrastructure in place from our other successful projects and national networks. We have partners in Europe and the USA, where we have established the same processes so that we can be most efficient and not have to reinvent the wheel. We will seamlessly share information to rapidly improve care for affected children around the world.",2022,2024,Hospital for Sick Children (Toronto),353430,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2022 +C19774,202007MS3,Predicting the risk of developing mental and substance use disorders due to COVID-19: machine learning applied to health service utilization data to facilitate access to effective treatments.,"COVID-19 has caused unprecedented demand on health care systems worldwide. Early indications suggest that the pandemic will lead to a surge in mental health and substance use disorders. This study aims to examine these mental and substance use implications through comparison of patient cohorts in BC, Canada based on their ""illness dose"" of COVID-19. In partnership with the Health Authorities and the BC Ministry of Health, we will deploy an online survey to assess these patient groups to detect the new onset or worsening of mental and substance use disorders that may be attributed to COVID-19. We will leverage Population Data BC, one of the world's largest collections of health services data containing individual-level, de-identified longitudinal data on BC's 4.7 million residents. We will link our survey results with data available at Population BC data, in order to retrospectively study the sociodemographic, service utilization, prescription drug use, employment, and environmental exposures of patients over the past 10 years. Using machine learning methods (Artificial Intelligence) to compare these different cohorts, each of which represents different ""doses"" of exposure to COVID-19, we will identify patients that are at increased risk of developing COVID-19-related adverse mental health outcomes. We will follow up with COVID-19 positive patients through a virtual clinic and assess existing treatment options for mental and substance use problems. Ultimately, we will have a system to predict increased risk of neuropsychiatric impact of COVID-19 on patients in BC, and to facilitate access of these patients early on to existing mental health services. This important data will allow Health Authorities to prepare for subsequent waves of COVID-19 with the tools required to rapidly mitigate its adverse effects on mental health and substance use.",2020,2021,University of British Columbia,149895,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19775,202203MM1,Prenatal exposure to maternal SARS-CoV-2 infection and neurodevelopment in children,"Previous pandemics and seasonal influenza studies have shown that in utero exposure to maternal viral infection results in a 2-7-fold increase in neurodevelopmental and neuropsychiatric disorders in adulthood. More severe disease and early exposure in pregnancy are associated with worse outcomes. Most studies have assessed these outcomes only in adults. Little is known about the effects of respiratory viral infection during pregnancy on children's neurodevelopment or socioemotional development. Pandemics increase psychosocial stress among pregnant individuals, which is also known to increase risk for neurodevelopmental and neuropsychiatric disorders. It is therefore imperative that studies track not only the developmental outcomes associated with viral infection during pregnancy, but also disambiguate the effects of viral infection from those of psychosocial stress. Here we build an ongoing pregnancy cohort study (n > 11,000) that enrolled individuals with SARS-CoV-2 infection during pregnancy, assessed exposure to pandemic-related hardship/stressors (e.g., job loss, social isolation), and psychological distress (e.g., depression and anxiety symptoms) among pregnant individuals. We propose to follow-up with this cohort to measure neurodevelopmental and socioemotional development in children. We will compare outcomes in two groups: children born to mothers with confirmed SARS-CoV-2 infection and children born to healthy mothers. The findings of this study will inform prevention and intervention efforts aimed at mitigating the damaging developmental effects of respiratory viral infection during pregnancy.",2022,2024,University of Calgary,190428.7,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts,2022 +C19776,202111WI2,"Prevalence of substance use and resilience behaviors and association with the COVID-19 pandemic: A linked data cohort study among young people of British Columbia, Canada.","We will use rich data sets at Foundry (an integrated youth services organization), the British Columbia (BC) Ministry of Health, and the Human Early Learning Partnership (an initiative to measure childhood development) to analyze how the COVID-19 pandemic has impacted young people ages 10-24 years across BC. Specifically, we will look at changes in substance use (with substances including alcohol, cannabis, and illicit drugs such as opioids) and the factors that protect against substance use or increase the risk for substance use. We will also examine how the pandemic has affected young people accessing services for substance use issues. We will then develop interventions for substance use by young people, taking into account the results we see for specific communities and populations in order to make the interventions relevant and appropriate. We anticipate that our project will help build capacity and a common language amongst stakeholders (from community to government) to advance intersectoral action to improve the health and resilience of young people during the COVID-19 pandemic.",2021,2023,University of British Columbia,388869.6,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C19777,202002OV3,Preventing SARS-CoV-2 infection by targeting human type II transmembrane serine protease activity,"The SARS-CoV-2 coronavirus causing COVID-19 has been declared a global emergency by the World Health Organization which has mobilized international scientists to collaborate in order to find therapies to counteract the virus's effects which can be devastating. The strategies need to be as vast as possible since we do not yet know if vaccines or other antiviral drugs will be efficacious. Our group had previously shown in the context of influenza infection that the human host has cell-surface proteases (called type II transmembrane serine proteases or TTSPs) that the virus requires in order to cleave a viral surface protein called hemagglutinin, itself essential for the virus to gain entry into the cell and further replicate using the host cell machinery. We had shown that small molecules inhibiting the activity of lung epithelial cell proteases were efficacious at significantly reducing influenza virulence demonstrating novel anti-viral properties of the compounds. The situation is similar with the SARS-CoV-2 virus but the protein found on the surface of the virus is different. This protein is called the spike glycoprotein (or S protein) and it requires cleavage by human host cell proteases of the TTSP family for its virulence. Our proposal will test protease inhibitors in models where cells are expressing the S protein and the most potent molecules will then be validated in lung organoids to verify their efficacy at reducing viral propagation. We have put together a team of molecular pharmacologists, chemists and virologist with access to containment level 3 facilities to rapidly assess the potential anti-viral properties of the compounds that we already have on hand. In addition, our team will be supported by Dr. Gary Whittaker, Cornell University, one of the world's expert in coronavirus biology. We believe that these conditions are very favorable for us to have a quick impact in the field and to deliver novel antiviral compounds for patients with COVID-19.",2020,2022,Université de Sherbrooke,642000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19778,202111WI2,Prioritizing the Public Health Workforce in Canada: Understanding Psychological Health and Intention to Leave During COVID-19,"The COVID-19 pandemic has revealed continued underinvestment and limited attention paid to the public health workforce in Canada. The pandemic has placed increased strain on an already burdened public health workforce. Public health staff are overwhelmed with demands of delivering vaccination programs and coordinating contact/case management in addition to attempting to deliver some core public health programs and services. There is a great amount of literature on the serious mental health impacts of the pandemic and 'intention to leave' among frontline health care workers in hospital settings. The effects of the pandemic on mental health and 'intention to leave' among the public health workforce in Canada however, are unknown. Identifying the extent of mental health and intention to leave impacts, who is most affected, and what factors influence these outcomes can help shape public health workforce planning, recruitment, and retention efforts needed for pandemic recovery in Canada. Additionally, understanding which organizational interventions are most effective in supporting mental health among at-risk groups in specific practice settings can support organizational planning and target resources toward those in most need for greater impact. The overall goal of this project is to gain an understanding about the nature and extent of mental health (burnout, anxiety, depression) and 'intention to leave' impacts on the public health workforce in Canada during COVID-19, which individual or work-related factors influence these outcomes, and what effective organizational interventions can promote and support the mental health of the public health workforce. We will work with senior public health decision-makers and public health organizations across Canada to ensure project relevance and feasibility and to support the timely dissemination of results to public health stakeholders for increased uptake.",2021,2023,McMaster University,176320.1,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C19779,202002OV5,Production of a recombinant S ( spike ) protein vaccine against SARS-CoV-2 and emerging coronaviruses,"In December 2019 a human coronavirus (CoV) outbreak causing pneumonia-like symptoms began, centered around a fish market in the Wuhan district of China. After the genomic sequence was determined the causative pathogen, SARS-CoV-2, showed 99.98% identity among 9 patients, was 88% identical to two bat SARS-like CoV, ~79% identical to SARS-CoV, and ~50% identical to MERS-CoV (Tan 2020 Lancet). SARS-CoV and MERS-CoV were responsible for severe human illness and mortality (~10% in 2002 and ~35% in 2013, respectively). Although understanding of SARS-CoV-2 and the COVID-19 disease is ongoing, it is believed human-to-human transmission is possible and the disease fatality rate is ~2-3%. In early February 2020, WHO reported >31,000 confirmed human infections, >640 deaths, and declared a Public Health Emergency of International Concern, presumably due to the possibility of a pandemic. The coronavirus 2019 outbreak is the third coronavirus outbreak causing a severe human disease in the past ~20 years. Currently a coronavirus prophylaxis vaccine and therapeutic drugs are not available. In this application we describe the investigation of vaccine candidates. Our team has manufacturing experience expressing a subunit Hepatitis-C virus vaccine candidate and has developed methods for industry-scale vaccine purification using removable purification tags (Logan 2017 Journal of Virology). This work will identify a CoV vaccine candidate that can proceed to the creation of a manufacturing grade mammalian cell line.",2020,2022,University of Alberta,450000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19780,202109EG8,Promoting protection of others to increase future COVID-19 booster shot vaccination intentions in younger adult Canadians: Evaluating the efficacy of a short video-based intervention,"New viral variants and the slowly decreasing immunity from the current COVID-19 vaccines have caused uncertainty about when the pandemic will end. Because of this, it is very likely that current vaccination recommendations will change, and booster shots of COVID-19 vaccines will be needed for continued protection against the virus. Younger adults (aged 18-39) have been identified as key spreaders of the virus. They also have the highest rates of vaccine hesitancy (delaying or refusing vaccination). Therefore, to protect Canadians of all age groups, it will be critical to promote vaccination in younger adults for the likely, upcoming COVID-19 booster shots. Currently, we are conducting an online study funded by McGill University to evaluate the effectiveness of an altruism-based video intervention we developed to decrease COVID-19 vaccine hesitancy. Early data shows that the video increases COVID-19 vaccine intentions in unvaccinated young Canadians. This study builds on our previous work and aims to randomize 2630 vaccinated Canadians aged 18-39 either to view a version of the altruism-based video, adapted to promote vaccine booster shots to protect others, or to read a text about recommended health behaviours concerning COVID-19 (control group). The goal of this study is to examine the impact of appealing to younger adult Canadians' sense of altruism to increase intentions to receive COVID-19 booster vaccines. Our research team has over 15 years of experience studying factors that influence vaccine hesitancy. We are partnering with the Public Health Agency of Canada (PHAC), the National Advisory Committee on Immunization (NACI), and the Institut National de Sante Publique du Quebec (INSPQ) to translate our findings into messages promoting vaccination that could be widely distributed. The results of our study will not only help to protect Canadians against COVID-19, but also prepare for future pandemics and other vaccine-preventable diseases.",2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,96665.98,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2021 +C19781,202111WI2,"Providing insight into and mitigating the impact of the COVID-19 pandemic on the occurrence, severity, complications, and long-term health effects of drug overdoses in people living with and without HIV in British Columbia, Canada.","The COVID-19 pandemic has exacerbated the ongoing drug toxicity and overdose (OD) crisis, resulting in an unprecedented rate of OD deaths in British Columbia (BC) since March 2020. People living with HIV (PLWH) have been disproportionately affected by substance use disorders and the ongoing OD crisis. As well, PLWH are at increased risk for negative indirect impacts of the pandemic, including increased levels of social isolation, loneliness, stress, anxiety, and substance use. More insight is needed in the extent of the impact of the COVID-19 pandemic on the occurrence of ODs, as well as the short and long-term health consequences of nonfatal ODs, in PLWH. We aim to study the impact of the COVID-19 pandemic on the occurrence of fatal and nonfatal drug ODs, and on the direct and long-term health outcomes after a nonfatal overdose (NFOD) in people living with and without HIV. We will use routinely collected health data on all PLWH in BC and a random sample of 10% of the general population. First, we will compare the incidence of fatal and NFODs before and during the COVID-19 pandemic, in people living with and without HIV. We will assess the severity of NFODs in terms of hospitalizations, complications, and duration of hospital stay. In addition, we will assess and compare trends in health care utilization and mortality in the six months after a nonfatal OD. Second, based on these analyses, and learning from the perspectives of community experts, health care providers, and policy makers, we will formulate recommendations for the care of PLWH who are at risk for or experienced an OD. These aim to reduce the risk for OD and adverse long-term health outcomes following a NFOD. This study will provide essential insights into the indirect impact of the COVID-19 pandemic on the coinciding OD crisis and HIV epidemic. These are urgently needed to inform targeted interventions to mediate the compounding effects of these three ongoing health crises.",2021,2023,Simon Fraser University,379983.68,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19782,202111WI2,Public safety salute: An ongoing surveillance and knowledge mobilization plan to support the needs of Canadian Public Safety Personnel impacted by the COVID-19 pandemic,"With the responsibility for the safety of our population, public safety personnel have been at the forefront of the COVID-19 pandemic, facing stressful and potentially traumatic situations, such as exposure to the coronavirus and a lack of personal protective equipment (PPE). Here, public safety personnel are at an elevated risk for a host of negative psychological impacts, such as anxiety, depression, PTSD, moral distress, and moral injury. Indeed, since the beginning of the pandemic in December of 2019, global research highlights the deleterious mental health impacts that the COVID-19 pandemic has had, and continues to have, on individuals in public service roles. Our targeted objectives are three-fold and include efforts to: i) understand the unique lived experiences and psychological impacts among Canadian HCPs resulting from their work during the COVID-19 pandemic through a national sample of multidisciplinary HCPs; ii) Identify risk and resiliency factors for psychological injury, the development of moral injury, and decreased functioning through a national sample of PSPs; iii) create knowledge translation and knowledge mobilization resources to support these workers.",2021,2023,McMaster University,394285.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19783,202107UIP,"QuaranTEENing: Understanding the Impacts of the COVID-19 Pandemic on the Mental Wellbeing and Health-Related, Social, and Environmental Behaviours of Teens","Using a teen-informed online survey and teen-led focus groups, we aim to understand how the COVID-19 pandemic restrictions have impacted the health and habits of teens, before and during public health measures were put in place, and after they were lifted. Specifically, the information we collect will be used to understand how COVID-19 has impacted, and continues to impact, the health-related behaviours and mental well-being of Canadian teens (aged 13-19 years) and the personal strategies they have used to cope over the course of the pandemic. Our existing for-youth-by-youth QuaranTEENing survey will be adapted to examine health-related habits and wellbeing of teens across Canada during COVID-19 in comparison to their current state now that some COVID-19 pandemic-related restrictions have been lifted and schools have re-opened. Teens who take part in the survey will be invited to participate in youth-facilitated focus groups that will further explore where teens socialized (in person/digitally) and spent their time (indoors vs outdoors), and provide in-depth information on the influence of the pandemic on mental wellbeing and substance use among teens. Our well-established Human Environments Analysis Laboratory Youth Advisory Council will be trained to take leadership roles in data collection and analysis, as well as help with the circulation of the final research outputs. The results of the study will be used to develop a resource for youth focused on building resiliency as well as generate appropriate policy, health promotion, and education recommendations at the provincial and school board levels.",2021,2022,Western University,118500,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19784,202109EG1,"Racial/ethnic inequities in diet quality and health during the COVID-19 pandemic in Canada: Trends, experiences and policy solutions","Black Peoples, Indigenous Peoples and People(s) of Colour (BIPOC) often have poorer diets and health than people in the majority of the population because of the difficult conditions in which they live. The negative economic and social impacts of the COVID-19 pandemic may cause the diets and health of BIPOC peoples to fall further behind. This research will: 1) study how the diets and health of adults in Canada and in each of the provinces who identify as BIPOC changed from pre- to mid- to late-COVID, and whether not being able to afford enough healthy food can explain some of these trends; 2) interview BIPOC adults who could not afford enough healthy food during COVID in Alberta, Ontario, and Quebec to understand their experiences and the types of programs and policies that might help them to improve their diet and health; and 3) ask decision makers and BIPOC adults in Alberta, Ontario, and Quebec which programs and policies should be prioritized to improve the diets and health of BIPOC peoples going forward. This research will help us to understand how and why the diets and health of BIPOC peoples changed during COVID in Canada, and what it was like for BIPOC adults in Alberta, Ontario, and Quebec to go through these changes. It will also show which programs and policies decision makers and BIPOC adults think are the most important to protect the diets and health of BIPOC peoples in Canada going forward.",2021,2022,Université de Montréal,121433.27,Human Populations,Black | Mixed,Adults (18 and older),Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C19785,202111WI2,Racialized and Immigrant Women at the Pandemic Frontlines: A Study of COVID-19 Pandemic Impacts on the Lives of Essential Workers in Ontario,"Due to the sudden emergence of the COVID-19 pandemic, there is limited research on its effects on gender, race and work, and yet current anecdotal evidence suggests more needs to be done in this area for policy and planning. Meanwhile, for many years now, there have been calls from various stakeholders to address issues related to gender and broader structural challenges affecting vulnerable workers in Canadian society (e.g., racialized women, issues related to pay equity; childcare services). Thus, in exploring the impacts and responses to COVID-19 in relation to racialized and immigrant women, this project is urgent and timely, and will produce original and significant work (both for scholarship and practice) by filling key gaps. Specifically, it will examine how social and economic realities, as well as mental health of racialized and immigrant women have been impacted by the pandemic. Second, the study will examine coping strategies adopted by racialized and immigrant women to manage the impacts of the pandemic on the mental health as well as social and economic well-being. Third, we also examine how strategies and programs implemented in response to COVID-19 by government institutions and employers were useful racialized and immigrant essential workers in the context of their mental health, social and economic realities. In so doing, this research will address an immediate problem, but also provide empirical evidence to begin to address longer-term structural issues. The study employs an embodied inquiry in the form of storytelling to understand how this group of women are navigating the pandemic at the site of work.",2021,2023,University of Toronto,143392.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C19786,202005VR1,Rapid bench-to-human development of safe and effective aerosol vaccine strategies against Covid-19,"The pandemic of Covid-19 caused by respiratory SARS-CoV-2 infection has brought the world to a standstill. The physical-distancing strategy currently implemented in the pandemic aims to prevent the majority of Canadians from being infected by SARS-CoV-2. While this is an essential short-term strategy to save lives, it will paradoxically leave the majority of our citizens without protective immunity against Covid-19. Thus, the majority of Canadians will be susceptible to the next waves of Covid-19. The only effective way to prevent new outbreaks from getting out of control is to establish herd immunity via implementing a safe and effective vaccination program prior to the next waves of Covid-19. High-risk Canadians including healthcare workers, seniors and indigenous people are especially in need of such vaccine-induced protective immunity. A global effort has been initiated to identify effective Covid-19 vaccines, testing a variety of vaccine platforms and strategies. Unfortunately, only a few of them are being developed and tested in Canada and almost none of them are designed to target respiratory mucosal immunity. To fill the gap, via the effort from a multi-disciplinary McMaster Team we have been rapidly developing innovative recombinant viral-vectored Covid-19 vaccine strategies to target the desired respiratory mucosal immunity. Our Team has internationally recognized reputation in bench-to-human translational vaccine research. Particularly relevant to the proposal is our strong expertise in advanced viral vector bioengineering, vaccine efficacy testing in small animal models at CL3 facility, clinical-grade vaccine production at GMP manufacturing facility, optimized inhaled aerosol vaccine delivery method, and clinical vaccine trials. We are confident that our project will make available to Canadians a superb, needle/pain-free vaccine strategy capable of potent respiratory mucosal protection against Covid-19.",2020,2021,McMaster University,1440738.75,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies | Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2020 +C19787,202002OV3,Rapid development of antiviral compounds to fight the COVID-19 outbreak,"The outbreak of a respiratory illness (COVID-19) in China at the end of December 2019 has been demonstrated to be caused by a new coronavirus. While health officials are using quarantine methods to try and prevent the spread of the infection, there are currently no treatments for the illness, which can be severe and even lead to death in 2% of cases. Here, we propose to build on our previous research with viruses of the same family, which include those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We have previously successfully engineered small proteins capable of blocking the activity of an enzyme of the virus that is crucial for its replication and for shutting down the human immune response. We plan on using a similar strategy to build blockers of the new virus. These will be extremely useful in better understanding the biology of the virus. Most importantly, we will use these blocking proteins to find chemical drug candidates that block the activity of the viral enzyme in infected cells, which can then be developed as therapeutics. Our method is rapid and cost efficient, and within the two years of this grant, we expect to have a number of lead candidate drugs. In order to achieve these goals, we have assembled a team of leading scientists with expertise in protein engineering of viral inhibitors (Sachdev Sidhu, University of Toronto), structural biology of viruses (Brian Mark, University of Manitoba), and development of chemical drugs (Roman Melnyk, SickKids Research Institute, Toronto). Our project also has the support of an internationally recognized leader in viral biology (Marjolein Kikkert, Leiden University, Netherlands) and a frontline clinician-scientist in infectious diseases (Samira Mubareka, Sunnybrook Health Centre, Toronto). Ultimately, this work will generate critical tools to better understand this new virus, and most importantly, will provide novel candidate drugs for direly needed therapies.",2020,2022,University of Toronto,664567.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19788,202109EG4,Rapid monitoring of the Impact of the COVID-19 pandemic on trends in drug supply and associated clinical outcomes,"The impact of the ongoing 2019 Coronavirus disease (COVID-19) pandemic on public health infrastructure and the broader health care system is a critical concern for policymakers, health care providers, and the general public. One major area of importance has been the impact of the pandemic on Canada's drug supply. The supply chain for prescription drugs can be taxed because of surges in demand associated with panic shopping, exacerbating existing drug shortages or causing shortages where none previously existed. Also there has been many announcements and misinformation regarding the repurposing of existing medications as potential treatments for COVID-19 which may increase demand for these drugs, despite limited or poor quality supporting evidence and potential harms associated with their use. Studies are needed to understand the impact of the pandemic on drug supply and utilization, and to confirm or refute anecdotal and theoretical reports of disease improvement and/or worsening due to the use of these medications.Our group of researchers from across Canada plans to use established infrastructure and national and provincial data to provide a rapid-response national picture of prescription drug use within the COVID-19 pandemic and measure and monitor the consequences of any shifts in medication use.",2021,2022,University of Toronto,386520.93,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research","Other secondary impacts | Medicines, vaccines & other technologies",2021 +C19789,202002OV1,"Rapid Research Response to the 2019 Novel Coronavirus Outbreak: Development of Targeted Diagnostics, Therapeutics and Comparative Pathogenicity Assessment","In 2019, the world has seen the emergence of a virus that causes pneumonia in humans, which has a high probability of resulting in complications that include acute respiratory distress syndrome and death in an estimated 0.2% to 5% of cases. Coronavirus disease 2019 (COVID-19) is caused by a virus endemic in wild animals that has adapted itself to infect humans. The World Health Organization (WHO) has declared the 2019 outbreak of the novel coronavirus (2019-nCoV), which is now officially named SARS-CoV-2, a global health emergency. Currently, there is no effective antivirals against this virus. The virus is genetically similar to the 2003 Severe Acute Respiratory Syndrome-related coronavirus (SARS) and shares many disease features with influenza virus infections. Our team will combine its multidisciplinary expertise to develop genetically engineered antibodies that can be used as therapeutics to limit the spread of the virus, as well as help identify the virus in patient samples. We will also develop a rapid genetic test for SARS-CoV-2 and measure the speed of genetic evolution of this virus compared to other coronaviruses that cause disease in humans such as SARS that caused the 2003 outbreak and the middle east respiratory syndrome virus (MERS). Finally, we will mass-produce the surface viral protein to enable the development of a prototype nasal-spray vaccine.",2020,2022,University of Ottawa,749999.25,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Diagnostics | Pathogen genomics, mutations and adaptations | Pre-clinical studies | Pre-clinical studies",2020 +C19790,202002OV4,Rapid Response to Emerging Serious Pathogen Outbreaks using Next-gen Data: R2ESPOND,"A new virus has been identified from Wuhan City in China from the coronavirus family (SARS-CoV-2), which is now responsible for more than 71,000 cases of illness (COVID-19 disease) in over 29 countries. Although there have not yet been any deaths in Canada, public health agencies are on high alert, as there is a real possibility of a serious epidemic. The WHO has declared COVID-19 a public health emergency of international concern. As of February 14th, five COVID-19 cases have been confirmed in British Columbia and based on travel patterns there is every reason to expect additional cases in BC. There are many unanswered questions regarding the virus, how it spreads and the disease that it causes. This information is needed for a data-driven response to this outbreak. We aim to use two types of next-generation data (next-gen genomics data and next-gen human data), along with a data integration tool called PLOVER 2.0, to answer these unknowns. The research team will 1)Carry out rapid genomic sequencing on patient samples to study the virus, how it spreads, how it evolves and predict which drugs will work 2)Develop knowledge of how the virus characteristics, along with a patient's previous health conditions, impact the severity of illness and how they recover from the illness 3)Develop a software tool (PLOVER 2.0) that will allow us to carry out this research and will also make the data viewable by key stakeholders such as Medical Health Officers. This work will not only generate critical knowledge about the SARS-CoV-2 virus but will also help develop a better understanding of health outcomes for infected patients. The knowledge generated and tools developed by this research can ensure an evidence-based and cohesive response to this public health emergency, here in Canada and internationally.",2020,2022,University of British Columbia,750000,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease transmission dynamics | Disease susceptibility",2020 +C19791,202005CMS,"Rapid review of the impacts of ""Big Events"" on people who use drugs and delivery of harm reduction and drug treatment services: Implications for strengthening systems in response to COVID-19","Big Events are significant disruptions (e.g. natural disasters) that create social instability and increase vulnerability to drug-related harms. The COVID-19 pandemic has the potential for significant short- and long-term impacts on risks and harms for people who use drugs, and harm reduction and drug treatment providers will need to be equipped to respond appropriately. This project is a rapid review of the impact of Big Events on drug-related risk and harms, and delivery of harm reduction and drug treatment services. We will identify previous research on the impacts of Big Events, and identify strategies and opportunities for harm reduction and drug treatment services to respond to the COVID-19 pandemic. We will use a variety of activities to disseminate findings and encourage rapid uptake into policy and practice, including an infographic, webinar, press release, and articles for the relevant workforce and people who use drugs. As well as informing the COVID-19 response, findings will provide insights to support strengthening health services and systems to respond to future disruptions.",2020,2020,Centre hospitalier de l'Université de Montréal (CHUM),37500,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19792,202002OV1,"Rapid, Ultrasensitive Clinical Detection of 2019 Novel Coronavirus (nCOVID-19) by Novel Microfluidic Electrochemical Nano-Biosensors","In December 2019, a novel coronavirus (2019-nCoV) emerged in the city of Wuhan, in China and has spread widely, including Canada. In a few weeks, the number of confirmed cases of COVID-19 infection has dramatically increased. Currently, 20-25% of confirmed cases have severe clinical presentations. With no vaccines nor specific treatments, early confirmation before progression to late stages would provide more time for effective supportive treatment. The traditional detection process requires that samples from sick individuals be transported to laboratories for manual processing. This is extremely inefficient and introduces a significant time-delay that has severe consequences for disease spread. Since January 2020, tests have become increasingly available for clinically suspected patients. However, despite the high sensitivity of these methods, they are not suitable for rapid and large-scale screening for multiple samples because of their long analysis time. Moreover, these methods need skilled personal to perform and not suitable for point-of-care testing. Most of these assays have not been yet adopted for COVID-19. The objective of this project is to develop a novel diagnostic tool for rapid detection of early-stage COVID-19. The device will have an impact to timely inform and refine strategies that stop the spread of the disease.",2020,2022,University of Calgary,596670,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C19793,202109EG2,Real-time assessment of SARS-CoV-2 variants of concern on ACE2 variants found in susceptible populations to understand mechanisms of heightened disease expression and to direct targeted vaccination efforts,"The COVID-19 pandemic has had greatest impact on marginalized populations including Indigenous, Black and Latino communities. A leading question of the COVID-19 pandemic is why distinct ethnic or regional groups exhibit increased infection rates, and why individual responses to infection are so varied, from asymptomatic to life-threatening pneumonia. One likely answer is genetic diversity in the gene encoding the cell-surface receptor protein for the SARS-CoV-2 virus, called ACE2. Genetic variation is common in ACE2, with distinct variants found in ethnic and geographic populations exhibiting heightened susceptibility to the pandemic, including Indigenous, Black and Latino peoples. Some ethnic group-associated ACE2 variants have been shown to alter binding to viral proteins, potentially underlying increased susceptibility. ACE2 genetic variants have also been implicated in comorbidities linked to poor COVID-19 outcomes, including diabetes, obesity and cardiovascular disease. Here, we propose to study how population variants of ACE2, including those found in Indigenous, and other susceptible populations, impact ACE2 functions that may alter COVID-19 disease. Given the rapid emergence of natural mutations of the SARS-CoV-2 virus underlying COVID-19, we will also test multiple variants of the viral spike protein for impact on binding to ACE2 variants. These include the mutations found in the Alpha, Beta, Delta, Gamma, and Lamda variants exhibiting increased transmissibility. We will identify human variants of ACE2 expressed in distinct ethnic groups that may confer enhanced susceptibility to infection to specific variants the virus. We will also identify how genetic variants and viral protein binding alters ACE2 function relevant to normal ACE2 physiology and pathophysiology linked to COVID-19 comorbidities. Our results will be critical for directing development of novel therapeutics and targeted population vaccination efforts in response to new viral variants.",2021,2022,University of British Columbia,162029,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity,2021 +C19794,202107UIP,"Reconnect: community-based action research to promote resilience and wellbeing in immigrant, refugee and racialized children and their families during and after the COVID-19 pandemic","Background. Immigrant and refugee populations have been disproportionately hard hit by the COVID-19 pandemic as a result of social and economic disadvantages. These inequalities, if unaddressed, can come at the cost of the wellbeing and adaptation of newcomer youth and contribute to the widening of long-lasting health and educational disparities between immigrant and non-immigrant populations. Objective. The Reconnect project adopts a community-based action research approach to investigate the experiences of newcomer youth and their families during and after the pandemic, and to look especially at how school-based interventions can mitigate the effects of the pandemic. Results from our study will contribute to the development of a best practice guide and arts-based dissemination tools for the promotion of wellbeing and resilience in the wake of the pandemic among racialized newcomer communities. Method. Based on the extensive work of our research team in Montreal during the pandemic, in collaboration with knowledge users and youth, we will adapt and implement specialized classroom- and community-based interventions for newcomer youth and their families. A total of 100 youth (ages 10-13) attending 6 classes for newcomers and 75 parents will participate in the Reconnect interventions. Qualitative (focus groups, fieldnotes) and quantitative data will be collected to explore the experiences of youth, parents, facilitators and teachers and changes in wellbeing (reduction in COVID-related stress, psychological distress) and resilience (positive school climate, family cohesion) from before to after the intervention. Results. In the short term we will support and empower migrant youth and their families in the wake of the pandemic, and rapidly disseminate critical insights to schools, teachers, and ministries of education. In the long-term, findings will support policy development to address social and health disparities between migrant and non-migrant communities.",2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,118485.78,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19795,202109EG2,Redefining eligibility of Social Assistance (SA) programs for vulnerable populations of Canada: A Data-driven Approach,"COVID-19 affected the most-vulnerable populations disproportionately, in Canada and globally. Though the government of Canada urgently rolled out social assistance (SA) programs to those who lost jobs and income because of the pandemic, many people were left out. Especially those, who already were most vulnerable, got even pushed further down during this pandemic, with no social assistance from the government. We are currently undertaking the COVID Impact project at the Bridge Engagement Center (the Bridge), a community-based research center in Ottawa, Canada. The COVID Impact project, aimed at learning the impact of pandemic on those who self-identify as homeless, at-risk for homelessness, low-income racialized minorities including Indigenous populations in Ottawa, Canada. Thus far, we have enrolled 400 people employing community based participatory action research approach and are now undertaking semi-structured interviews. We propose to build a data-driven model, based upon the data from the COVID Impact project, to create an inclusive social assistance program, leaving no one behind. This model will utilize the rich data from the 400 people enrolled at the Bridge, focusing on social determinants of health (SDH). We will finalize the SDH more relevant to the people with lived experience and co-create the model. Based on the criteria co-developed through this project, the provincial and federal governments will be able to redefine SA eligibility and reach the most vulnerable populations. This proposed project will also help guide programs for other low- and middle-income countries where COVID-19 affected those living on the margins of the society. .",2021,2022,Ottawa Hospital Research Institute,392731.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19796,202111WI1,Reducing Maternal Perinatal Mental Health Problems in Times of Service Shortage: A web and telephone-based Intervention,"Women of child bearing age have had the largest increase in anxiety and depressive disorders of all age groups since the onset of the pandemic (Lancet, 10/21). As documented in over 300 studies and 15 meta-analyses, maternal mental health issues exert a toll on mother, family, and newborn. In Canada, pregnant women have reported levels of depression 2-3 times higher than pre-pandemic levels. In Quebec, >19 000 persons are on the government waiting list for receiving mental health services. Offering effective population-based prevention programs to deal with mental health problems -a wider impact of COVID-19 pandemic- is thus more important than ever in a context where curative/therapeutic services are lacking. To advance mental healthcare among a high-risk population, we will test the efficacy of a virtual care intervention (telephone-based) initiated early in pregnancy to prevent postpartum depression at 2 and 6 months after childbirth (points of peak prevalence). The Parents & Babies intervention comprises 8 online modules and 10 telephone sessions by a trained coach. Participants' partners are encouraged to take part in the intervention. This randomized controlled trial will enroll 510 Quebec women with mild to moderate depression from diverse socioeconomic and cultural backgrounds. The project will maximize health benefits within a rapid response timeframe by 1) providing timely web-based and telephone support; 2) potentially prevent maternal depression, anxiety and child development issues associated with maternal mental health problems; 3) identify a potentially effective and cost-effective model of preventive care to ameliorate the wider negative impacts of COVID-19; 4) by comparing RCT data to our 3 ongoing perinatal mental health observational studies, generate new knowledge on the indirect and wider consequences of COVID-19 on maternal and child health.",2021,2023,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",421874.22,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19797,202002OV1,Reducing the Health Care Resource Burden from COVID-19 (SARS-CoV-2): Rapid Diagnostics to Risk-Stratify for Severity of Illness,"Key to an effective response to the current novel coronavirus (COVID-19) outbreak is a method to rapidly identify emergency department patients presenting with symptoms of COVID-19 and are at high risk of progressing to severe illness and death. At University Health Network, our team represents a deeply experienced group of critical care doctors and infectious disease researchers who can immediately respond to the global need to provide an accurate diagnosis of respiratory illness-the main feature of COVID-19-at the front lines of patient care. We have recently developed a 40 minute diagnostic test to determine lung quality for transplantation. Recent scientific studies from China clearly show that the body's development of respiratory distress as a response to potential COVID-19 infection produces an identical injury profile that would be detected by our diagnostic test. We will work alongside SQI Diagnostics, our Canadian partner committed to developing diagnostics for lung health, to adapt our test towards the development of RALI-Dx (Rapid Acute Lung Injury Diagnostic). This diagnostic can be used by hospital emergency departments to screen for lung sickness and the likelihood of COVID-19 infection. An important part of our CIHR-supported research study is a commitment from our Chinese collaborators to safely test our diagnostic first on COVID-19+ blood samples to make sure the test is highly accurate before hospital use. With our 40 minute RALI-Dx test, we will: -Quickly identify the highest risk patients in need of immediate care -Identify lower risk patients who require at-home monitoring -Reduce the current major stress on health care facilities Additionally, new COVID-19 therapies are being rapidly developed around the world, and the first step will be to identify which patients will benefit the most from these treatments. With RALI-Dx, hospitals everywhere can better manage patient care and provide an accelerated response to the COVID-19 outbreak.",2020,2022,University Health Network,728026.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2020 +C19798,202109EG9,REMOTE Study: Longitudinal Monitoring of the Incidence of SARS-CoV-2 Infection and Immunity Levels in Long-term Care Facilities,"Approximately 11% of COVID-19 cases and 73% of all COVID-19 deaths in Canada have been in long-term care (LTC) homes, affecting both their residents and staff. With the rapid vaccination of the residents and staff in LTC facilities, the questions now are how to effectively monitor their risk of infection, and to quantitatively evaluate the protection levels and strategies for better implementing post-vaccination care to the residents. Technically, none of the commercially available rapid tests and wearable devices have been effectively utilized in Canada for longitudinal monitoring of SARS-CoV-2 markers and host immune response in LTC residents and staff, as these technologies are inefficient, lengthy, costly, not digital, often invasive, and require skilled personnel to operate. We propose to fill this critical gap in effective self-testing of infection and immunity levels through a unique vital signs and immunity level monitoring system integrated with a machine-learning harnessed web-app (REMOTE). Once pilot-tested and implemented, the digital REMOTE technology will enable accurate and non-invasive monitoring of LTC residents and staff through simultaneous longitudinal monitoring of 1) vital signs using smartwatches and 2) risk of viral infection and protection levels using digital saliva testing kits. With the partnership with Brenda Strafford Foundation, our project will benefit to protecting at-risk LTC residents while helping them remain socially and emotionally connected. It will represent an opportunity to provide evidence-informed recommendations for the development of standards for staffing and infection monitoring, prevention, and control in LTC homes. The outcomes of this research in the short term will provide enhanced uptake of accurate rapid tests and digital technologies by LTC staff and residents, and in the longer term, will build the basic infrastructure for a shift in home-based medicine and remote monitoring of diseases.",2021,2022,University of Calgary,395000,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2021 +C19799,202002OV4,RIsk of environmental Surface and air Contamination in COVID19 (RISC-COV),"This study has three goals. First, we will collect clinical and epidemiologic information about COVID-19 in Toronto and Peel region to share with ISARIC studies of the risk factors for, clinical features and outcomes of this infection in Canada and around the world. Second, we will collect data about how long patients with this infection shed virus, and whether this virus can be found on surfaces and in the air around patients with this infection, in order to help guide infection prevention practice. Third, we will systematically collect samples containing the virus, serum and cells of the immune system, in order to create a biobank that can be shared with investigators developing vaccines and treatment for this disease.",2020,2022,Sinai Health System (Toronto),369855,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Environmental stability of pathogen | Disease transmission dynamics",2020 +C19800,202109EG2,Safety and Efficacy of Preventative COVID Vaccines- STOPCoV ( Phase 2),"There has been rapid approval of the COVID-19 vaccines. The participants in the initial research were mostly Caucasian with an average age of 50 years and with little underlying illness. More information is needed as to how well the vaccines work and are tolerated in older persons and in a more diverse population like Ontario. STOPCov has enrolled 911 persons over 70 years of age and is comparing them to 380 persons 30-50 years who received COVID vaccine. Participants completed an e-consent and were assigned a unique participant number to maintain confidentiality. They were emailed study documents and completed on-line questionnaires about their demographics, underlying illness and prescription medications and any prior COVID-19 diagnosis. They completed a 7 day on-line diary about any local (pain, swelling, redness) or systemic reactions (fever, chills, muscle aches) after each COVID-19 vaccine dose. More information is also needed on how well older individuals respond to the vaccine. In STOPCoV this is being determined by measuring the levels of antibodies or proteins produced in response to the vaccine. To do this part of the study, consenting participants collect their own blood spots from finger pricks with a lancet, apply the blood spots to a filter paper and mail them to the research center for analysis. Written and video instructions on how to do this were provided. It is becoming clear, that older ( and later younger) individuals will be offered a ""booster"" or third dose of vaccine. Hence this new phase of the study is proposed to determine the antibody response to a third vaccine dose, to follow the antibody levels for an additional year and to complete and additional 7-day diary about any side effects to the third dose. We will also study the impact of race, gender, and underlying illness (such as diabetes, high blood pressure, heart, liver or kidney disease) on vaccine safety and effectiveness. Our results will be shared with public health officials.",2021,2022,University Health Network,394316.65,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Phase 2 clinical trial,2021 +C19801,202005VR1,SARS-CoV-2 immunization strategies to enhance protective immunity with reduced risk of antibody-dependent enhancement (ADE),"A pandemic of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) that emerged from China late in 2019 is currently underway resulting in worldwide severe morbidity and mortality. Thus, a safe and effective vaccine is urgently needed to fight virus propagation. In this project, after identifying and engineering the immunogens, we will translate towards SARS-CoV-2 a versatile, potent and immunostimulating nanotechnology platform recently developed in our laboratory, which not only will adequately present the vaccine materiel to the host immune system but also enhance its immunogenicity, while eliminating the risk associated with the so-called antibody-dependent enhancement (ADE). The gathered investigative team integrates a unique set of complementary knowledge including biophysics, protein engineering, virology and immunology, which is perfectly suited to rapidly address the health challenges of the COVID-19 pandemic, and has the necessary expertise and state-of-the-art infrastructure to conduct the proposed research.",2020,2021,Université du Québec à Montréal,467086.5,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19802,202005VR3,SARS-CoV2 therapeutic discovery through genetic screens and repurposing drugs that target essential virus-host interactions.,"The worldwide pandemic of COVID19 caused by the virus SARS-CoV2 has caused over 270,000 human lives and worldwide economic collapse. While public health measures such as social distancing and shutdown of non-essential businesses have been effective at slowing virus spread, restarting society and economies in Canada and around the world will require intensive testing and contract tracing, and ultimately effective treatments and vaccines. In this proposal our goal is identify existing therapeutics that can be re-purposed to treat SARS-CoV2 infections. During an infection viruses must hijack host machinery and regulatory pathways in order to reproduce, and some of the pathways used by viruses are the same ones that are dysregulated during human diseases such as metabolic diseases and cancer. Thus, it is likely that therapeutics designed to treat metabolic diseases and cancer also inhibit SARS-CoV2 infections. However, the specific machinery and regulatory pathways used by SARS-CoV2 remain unknown and the potential inhibitors undiscovered. Our strategy is to identify the host machinery and regulatory pathways the virus needs to grow, and then test drugs that target these proteins to see if they inhibit SARS-CoV. Finally, many different types of coronaviruses likely also use the same host machinery and regulatory pathways so the inhibitors we discover might also be effective against other coronaviruses so could help society prepare for future coronavirus outbreaks and avoid future pandemics.",2020,2021,University of Saskatchewan,336957,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19803,202007MS3,Screening Student Resiliency and Mental Health Indicators During School Re-Entry,"COVID-19 displaced millions of students from their schools, teachers, and peer groups. Early data proclaimed everything from a second ""mental health pandemic"" wave to significant expressions of strength and resilience. The primary research question is: What are the self-reported mental health needs and resiliency indicators of students returning to school amidst COVID-19? This information is urgently needed by schools to ensure effective, appropriate, and time sensitive mental health supports are available to returning learners in their metropolitan schools (Catholic and public) in two major Canadian cities. This study will measure behavioural and mental health functioning and resilience in a large sample (N approx. 3000) of metropolitan school district students at the time of school re-entry and again at 3, 6, and 9 months post school re-entry. Students will complete measures of COVID-19 health behaviours, mental health symptoms and adaptive behaviours, and resiliency. Results will inform strategic planning related to student services for these school districts and assist in the development of system-wide intervention and resource allocation for students returning to school in Fall, 2020. Knowledge translation activities will include dissemination of results to the metro school districts via reports, data webinars, infographics, social media platforms, and peer-reviewed publications. In summary, the present study will assist four major metro school districts to gather screening data useful for prioritizing district-wide initiatives that can inform strategies to build on identified strengths and remediate self-reported learning, behavioural, and social-emotional needs of students upon school re-entry.",2020,2021,University of Calgary,149315.25,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C19804,202107UIP,"See us, hear us 2.0-Mental health and well-being impacts of the COVID-19 pandemic on children, youth, and families in Saskatchewan","It is generally believed that school-aged children and youth are impacted by COVID-19 to a lesser degree--certainly when compared to older adults--but this is based on a relatively narrow set of outcomes such as case rates, hospitalizations, and deaths. There are still many questions that need answers. Personal stories about these challenges abound but, to date, there is no systematically collected information about these challenges. The aim of this project, therefore, is to estimate the impact of the second year of COVID-19 pandemic on the prevalence and severity of mental health and quality of life among children (8-11y), adolescents (12-15y), and youth (16-18y) and the need for and receipt of mental health services. Building on a study currently being completed in terms of recruitment of child and parent/caregiver dyads in Saskatchewan, this project extends it to the future: investigating children/youth mental health into the second year of the pandemic. Four questions are addressed: 1. Are children's and youth's mental health and quality of life outcomes different in 2022 in comparison to the outcomes in April-July 2021? 2. What coping strategies are utilized, if any, and what is the association between these coping strategies and mental health and quality of life outcomes? 3. What role have mental health services played in helping young people deal with the challenges of the pandemic? 4. How are sociodemographic characteristics (e.g., sex at birth, self-declared gender, disability, family income, culture/ethnicity, immigrant status) associated with these variables? The ultimate aim is to provide evidence-based recommendations to decision-makers and practitioners that, if acted on, will improve the mental health well-being of children and youth in Saskatchewan.",2021,2022,University of Saskatchewan,118441.54,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19805,202002OV8,Senior public health leadership during the 2019 novel coronavirus outbreak: Comparative approaches to mitigating the spread of infectious disease and its social consequences in Canada and abroad,"During an infectious disease outbreak, senior public health leaders work diligently to contain its spread, manage the medical and social impact, and try to counter misinformation and prevent discrimination. The emergence of a novel coronavirus has vividly demonstrated the need for clear, timely, and accessible information from trusted and authoritative public figures. In many countries, the virus has been accompanied by the spread of false information, racism, and panic. These factors heighten the risks of the virus for individuals and communities and complicate the challenges public health leaders face in containing it. The proposed research will systematically analyze the ways in which public health leaders in Canada and four other countries with similar public health systems are addressing the biological and social risks of the novel coronavirus in their public messaging across a range of platforms, including social media. Using text analysis of official communications and one-on-one interviews with public health leaders, we will analyze and compare how government spokespeople, including Chief Public Health Officers and Ministers of Health, are communicating medical advice, addressing misinformation, and tackling racism. We will also examine whether and how they identify different impacts of the virus based on sex and gender. The project will additionally collect public polling data to investigate the extent to which these public health communications are received, understood, and trusted by citizens in different countries. As a result of this project, we will have a better understanding of who speaks for the government during an outbreak, the kind of information they share, and how their messages are understood by the public.",2020,2022,University of Ottawa,0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C19806,202004SBC,Sex as a Biological Variable Supplement - Innovative therapeutic approaches for the 2019-novel coronavirus,"The 2019-novel coronavirus (SARS CoV-2) is a major sanitary and economical threat to all countries. Development of effective antivirals is a major global priority especially early in the epidemic when vaccines are unavailable. This proposal aims at discovering and evaluating active compounds by rational design through 3D modeling of key viral proteins and also by analyzing cellular gene signatures induced by the virus. In-depth evaluation of selected compounds will include in vitro, ex vivo (human bronchial epithelium tissues) and in vivo (animal models) studies. These approaches, mostly based on drug repurposing (new indication for an existing drug), will result in rapid identification of anti-SARS CoV-2 compounds with accelerated clinical development.",2020,2021,Université Laval,37335,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C19807,202004SBC,Sex as a Biological Variable Supplement - Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),"SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",2020,2021,Unity Health Toronto,37500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Clinical trial (unspecified trial phase)",2020 +C19808,202004SBC,Sex as a Biological Variable Supplement - Preventing SARS-CoV-2 infection by targeting human type II transmembrane serine protease activity,"The SARS-CoV-2 coronavirus causing COVID-19 has been declared a global emergency by the World Health Organization which has mobilized international scientists to collaborate in order to find therapies to counteract the virus's effects which can be devastating. The strategies need to be as vast as possible since we do not yet know if vaccines or other antiviral drugs will be efficacious. Our group had previously shown in the context of influenza infection that the human host has cell-surface proteases (called type II transmembrane serine proteases or TTSPs) that the virus requires in order to cleave a viral surface protein called hemagglutinin, itself essential for the virus to gain entry into the cell and further replicate using the host cell machinery. We had shown that small molecules inhibiting the activity of lung epithelial cell proteases were efficacious at significantly reducing influenza virulence demonstrating novel anti-viral properties of the compounds. The situation is similar with the SARS-CoV-2 virus but the protein found on the surface of the virus is different. This protein is called the spike glycoprotein (or S protein) and it requires cleavage by human host cell proteases of the TTSP family for its virulence. Our proposal will test protease inhibitors in models where cells are expressing the S protein and the most potent molecules will then be validated in lung organoids to verify their efficacy at reducing viral propagation. We have put together a team of molecular pharmacologists, chemists and virologist with access to containment level 3 facilities to rapidly assess the potential anti-viral properties of the compounds that we already have on hand. In addition, our team will be supported by Dr. Gary Whittaker, Cornell University, one of the world's expert in coronavirus biology. We believe that these conditions are very favorable for us to have a quick impact in the field and to deliver novel antiviral compounds for patients with COVID-19.",2020,2021,Université de Sherbrooke,37500,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +C19809,202004SBC,Sex as a Biological Variable Supplement - Understand the high pathogenicity and zoonotic transmission of the COVID-19 virus: evasion of host innate immune responses,"Coronaviruses are not new to humans. The human coronaviruses OC43 and 229E were discovered as early as in the 1960s. Both viruses cause common cold, a mild infection of our upper respiratory tract. However, the story started to change in 2002 when SARS broke out in China and other countries. This outbreak was caused by a new coronavirus which originally came from bats. Most importantly, this SARS coronavirus is highly pathogenic, with a fatality as high as 10%. Ten years later, a more deadly coronavirus caused the MERS outbreak. Now, a new coronavirus came back, is raging in China, may cause a global pandemic if not controlled. This new virus, COVID-19 (or SARS-CoV-2), has infected more and killed more than the total number by both SARS and MERS. Two urgent questions need to be addressed. How did these coronaviruses transmit from animals into humans? What have made them so pathogenic and lethal? Humans are protected from viral diseases by the immune system. These pathogenic coronaviruses must have found ways to evade the immune responses so that they can spread in humans and cause fatal illness. We thus propose this research to elucidate how this COVID-19 virus does this. The findings will identify the key viral genes that suppress immune responses by blocking essential signaling pathways. Our results will open new avenues for the development of effective interventions to halt the COVID-19 break.",2020,2021,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,37500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Immunity | Animal source and routes of transmission",2020 +C19810,202107UIP,Sharing Youth's Storiis of COVID: Youth voice as a basis of understanding the broader impacts of adaptations in youth programming with a focus on micro populations,"This study invites 1,000 Canadian youth who are LGBTQ2, rural, Indigenous, racialized, in-care, and living with disabilities to share how COVID-19 and the restrictions it caused affected them. The study is led by Heather Lawford (Bishop's University) and Heather Ramey (Brock University) in collaboration with Tanya Halsall, Yana Berardini, Nishad Khanna and The Students Commission of Canada (SCC), a national charitable youth organization. SCC will support other organizations across Canada to engage in the research. Adults and youth from these organizations will form advisory groups to participate in every aspect of the process. Together, they will explore how unique populations of youth might have been affected in different or similar ways by program and service changes that schools, recreation centres, doctors, employers, families etc. made throughout the pandemic. How did these changes affect young people's mental and physical health, their growth and development, and their relationships? Did some changes improve life for some youth? Were some changes more harmful than others? Findings from this study will be shared with all the participating youth and organizations, as well as at SCC's annual national #CanadaWeWant events. During these, youth members of the study's advisory committees will present findings to decision-makers, policy-makers and youth. The advisory groups will also advise on other ways to share knowledge from this study with their communities. Results will inform governments and organizations know what changes they made during COVID-19 that they should keep doing: for example, increased on-line services that improved access to mental health counsellors. It will also increase understanding of inequities and harms that some youth from these populations experienced, so that these can be addressed through post COVID-19 programming and services. Youth voice and participation integrated with research is critical if we are going to ""build back better.""",2021,2022,Bishop's University,118349.11,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Disabled persons | Indigenous People | Sexual and gender minorities | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19811,202109EG8,Short-term effects of the COVID-19 pandemic on infant socioemotional and neurodevelopment,"Previous pandemics and seasonal influenza studies have shown that in utero exposure to maternal viral infection results in a 2-7-fold increase in neurodevelopmental and neuropsychiatric disorders in adulthood. More severe disease and early exposure in pregnancy are associated with worse outcomes. Most studies have assessed these outcomes only in adults. Little is known about the effects of respiratory viral infection during pregnancy on children's neurodevelopment or socioemotional development. Pandemics increase psychosocial stress among pregnant individuals, which is also known to increase risk for neurodevelopmental and neuropsychiatric disorders. It is therefore imperative that studies track not only the developmental outcomes associated with viral infection during pregnancy, but also disambiguate the effects of viral infection from those of psychosocial stress. Here we build an ongoing pregnancy cohort study (n > 11,000) that enrolled individuals with SARS-CoV-2 infection during pregnancy, assessed exposure to pandemic-related hardship/stressors (e.g., job loss, social isolation), and psychological distress (e.g., depression and anxiety symptoms) among pregnant individuals. We propose to follow-up with this cohort to measure neurodevelopmental and socioemotional development in infants at 1y of age. The findings of this study will inform prevention and intervention efforts aimed at mitigating the damaging developmental effects of the COVID-19 pandemic on infant development.",2021,2022,University of Calgary,318610.16,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19812,202002OV5,Shutting down emerging Coronaviruses in humans now and in the future,"In December 2019, a pneumonia associated with the 2019 novel coronavirus SARS-CoV-2 emerged in Wuhan, China. This disease is now named COVID-19. Over 73,000 people have been infected worldwide and over 1,700 people have died from the disease. There is no sign that the rate of new infections and deaths are levelling off or showing signs of declining. Similar coronavirus outbreaks in the future are always a risk and must be addressed now. The goal of this proposal is to establish and test an effective vaccine for SARS-CoV-2. In addition, we will develop a coronavirus vaccine bank containing hundreds to thousands of potential vaccines that can be used at the start of the next coronavirus outbreak. This will give us a head start in trying to treat patients early with the goal of reducing the spread of the disease and subsequent fatalities.",2020,2022,Western University,749130,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Pre-clinical studies,2020 +C19813,202107UIP,Socioeconomic gradients in early child development and COVID-19: A pre-post study of kindergarten children in multiple Canadian jurisdictions,"Home, early learning and play environments, and community resources play an important role in shaping children's development. Many of these resources and supports were closed or became disrupted during the COVID-19 pandemic in Canada, and the impact of these disruptions on young children's development is unknown. This study will look at the development of kindergarten children attending schools in 2021/22, using the Early Development Instrument (EDI), a teacher-completed checklist of children's physical, socioemotional, and cognitive development. EDI data have been regularly collected across Canada in most provinces and territories since 2004. These data have been linked with neighbourhood socioeconomic status (SES) data from Census and Taxfiler databases. The goal of our study is to see whether the development of 5-year-old children attending kindergarten in 2022 differs from the development of children who attended kindergarten before the COVID-19 pandemic. We want to know whether COVID-19 may have caused changes in children's development, and whether these changes vary between places where children live and between different groups of children (e.g. based on their sex at birth, their first language, family income, and neighbourhood mix of race/ethnicity). Our project will look at different aspects of children's health: physical, mental, and cognitive development, and we will explore whether disruptions in schooling and childcare had an impact on children living in different parts of the country. This study will tell us about the impacts of the COVID-19 pandemic on kindergarten children's development, which is important for later academic achievement and health. It will provide information to help us identify groups of children who may be at particular developmental risk. Our study will offer timely and specific information to educators, health professionals and governments to help prevent possible long-term negative impacts of the pandemic on young children.",2021,2022,McMaster University,73837.35,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19814,202002OV7,Spatial and social patterning of COVID-19 prevention and transmission in Canada: Investigating the impacts of risk perception and preventive behaviour on individual activity space,"Emerging and re-emerging global infectious diseases are presenting unprecedented public health challenges, resulting in negative, long-lasting health, sociocultural and economic consequences for individuals and communities around the world. As a global city, Toronto is home to one of the most highly-travelled populations in the world. It has been a significant receiving geography of a number of global infectious diseases. The project aims to understand the relationships among health risk perception, community prevention behaviour and individual activity space during the on-going global COVID-19 outbreak. Disease transmission in an urban centre is directly influenced by individual activity space and the effectiveness of preventive measures taken in a community, which is largely shaped by perception of the disease and its risk. The project will (1) explore the perception of COVID-19 and its risks among groups with different immigration status, socio-economic-demographic characteristics within Toronto's Chinese community; (2) examine how risk perception shapes prevention behaviour and individual activity space; and (3) assess how activity space is influenced by risk perception, prevention practices, and other factors through spatial-quantitative, mapping and qualitative analysis. Data will be collected from a community survey on risk perception, prevention behaviour and daily mobility, and focus groups on coping strategies. The project will contribute to the global response to the COVID-19 outbreak by providing evidence-based findings on community prevention behaviour in a large urban hub. It will reveal local perspectives, citizen approaches and community practices as outbreak response effort, and enhance our understanding of the cultural dimensions of the epidemic. It will yield implications for public health response in setting policies under time constraints and uncertainty, allocating resources, identifying high-risk groups and setting vaccine priority.",2020,2022,Ryerson University,141787.5,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C19815,202111WI4,"Standing Together: Strength, Resilience, and Indigenous leadership as the Pathway to Pandemic Responses","The First Nations Health Authority (FNHA) works with First Nations in BC to respond to the COVID-19 pandemic with culturally safe, community-driven services. First Nations health leaders expertly navigate barriers and facilitators intrinsic to pandemic response, however, there is a gap in awareness across the system in relation to strategies, successes and opportunities for improvement related to COVID-19. Our project brings together Indigenous leadership to tell this story: we explore the long-term social, economic and health impacts of COVID-19 for Indigenous Peoples in BC, and how Indigenous leadership honours and upholds First Nations rights to decision-making in Indigenous-led pandemic response. Our story is simultaneously about systemic inequities and Indigenous resistance and resilience. Using an appreciative inquiry approach, we will engage Indigenous leaders across urban, rural and remote settings to identify community-driven and self-determining efforts that protect First Nations Peoples in BC from the wide-reaching effects of COVID-19, including but limited to: mental health, substance use, delayed access to care and community health care, and workforce resilience and burnout. We will review both indexed and non-indexed literature about the long-term impacts of COVID-19 on Indigenous populations in Canada, the United States, Australia, and New Zealand. Then, we will gather stories and co-develop an Indigenous health emergency preparedness framework and toolkit, and, a public facing report with wise and promising pandemic response strategies. Leadership from all five BC health authority regions and FNHA will be invited to participate in story gathering and data validation activities. Ultimately, our project documents First Nations leadership during the COVID-19 pandemic and creates outputs to guide future pandemic response specific to First Nations in BC.",2021,2023,Simon Fraser University,381618.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts | Economic impacts,2021 +C19816,202109EG1,"Strengthening the capacity of healthcare providers to reduce the impact of COVID-19 on African, Caribbean, and Black communities in Ontario","African, Caribbean, and Black communities (ACB) are vulnerable populations in terms of their health risks, receipt of adequate care and chance of recovery. There is an urgent need for action to mitigate ACB health risks and strengthen the capacity of healthcare systems. The main objective of this project is to accelerate the use of high quality and real-time evidence collected on the contextual vulnerability and challenges experienced by ACB communities to develop, implement and evaluate community-driven solutions to structural inequalities including systemic racism that continues to hamper the response and recovery from COVID-19. We will co-develop a minimum of four virtual educational modules for health providers aimed at: 1. Social determinants of health and health inequities; 2. Critical health and racial literacy (e.g. privilege, racism, implicit bias and the intersectionality of identities); 3. Organizational and provider cultural competency and safety; and 4. COVID-19 and its impacts on health. We will also develop an interactive website to house the emergent modules, as well as resource toolkits, community fact sheets, policy tools and guidelines. Project evaluation activities will occur throughout the year including the development of a project logic model and evaluation framework to measure program outputs and impacts. Our project team consist of community partners, healthcare providers and knowledge users from diverse backgrounds and disciplines across Ontario: Alliance for Healthier Communities, Canadians of African Descent Health Organization, African Caribbean Council on HIV and AIDS in Ontario, Somerset West Community Health Centre, Women's Health in Women's Health CHC, AIDS Committee of Ottawa and TAIBU CHC. Moving forward we will work to extend our partnerships and focus on expanding training and capacity building activities to reach and meet the needs of health provider groups and settings throughout the province and nationally.",2021,2022,University of Ottawa,367530.91,Human Populations,Black,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Indirect health impacts | Health service delivery | Individual level capacity strengthening | Institutional level capacity strengthening,2021 +C19817,202002OV3,"Synthesis, Structural Studies and Evaluation of Inhibitors of the 3CL Protease of SARS-CoV-2 as Potential Drugs for Treating Infection","The coronavirus, formally known as SARS-CoV-2, is viewed as a global health emergency since its 1st appearance in Dec 2019. Coronaviruses are spread through close contact from coughs & sneezes, but may also spread from animals, feces or contaminated surfaces. As of Feb 2020, > 44,730 people are infected in China and >1114 have died (97 in a single day). Seven cases have been reported in Canada. This disease, Covid-19, could become a pandemic unless appropriate measures or cures are found. In past work on a similar coronavirus, Severe Acute Respiratory Syndrome (SARS) virus prevalent in 2002-03, our group modified inhibitors for a protein it produces and requires, namely the 3CL protease. This protein is essential for replication and infectivity of that SARS virus. Genome sequencing of the current virus, SARS-CoV-2, demonstrates that it also has a 3CL protease that is nearly identical (96% the same). Of the 306 amino acid residues in the chain that makes the 3CL protease of the SARS-CoV-2 virus, only 12 are different and they are highly similar in properties. Recently, chemical compounds we previously made for the original SARS 3CL inhibition were slightly altered and one new derivative was shown to cure cats of feline infectious peritonitis (FIP), a natural mutant of feline enteric coronavirus (FECV). This infection is almost always fatal, but the key compound effected cures or significant remissions in all the cats. We propose to make the key compound and a series of its analogs by chemical synthesis. In addition, we propose to clone and express the 3CL protease (non-infectious) of the coronavirus SARS-CoV-2. We propose to assay all synthetic compounds as inhibitors of the 3CL protease, and to obtain X-ray crystal structures of the protease with these potential drugs to facilitate further inhibitor design. In a virology lab, compounds will be examined for their ability to kill the virus in infected cell lines.",2020,2022,University of Alberta,0,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19818,202111WI1,Systematic implementation and impact evaluation of data-driven cardiac surgery triaging tools to optimize operational efficiency and enhance patient outcomes during the COVID-19 pandemic and beyond,"The COVID-19 pandemic has precipitated a health care crisis that disrupted the care of patients with cardiovascular and other health conditions. Non-emergent procedures were deferred amidst this crisis to create capacity for COVID-19, creating surgical backlogs around the globe. This growing surgical backlog of patients with advanced cardiac disease creates a dilemma for clinicians and administrators, as these patients require monitoring in the intensive care unit (ICU) after surgery and may potentially compete with the resource needs of those with severe COVID-19 infection. On the other hand, prolonged wait times are associated with worsening disease severity, unplanned hospitalization and death. In response to this challenge, our group developed the CardiOttawa Length of Stay (LOS) and Waitlist Scores as evidenced-based decision support tools to prioritize high-risk patients needing definitive surgery while preserving ICU and hospital capacity, improving patient outcomes and reducing health care resource consumption. The CardiOttawa is founded on high quality, population-based data and has been used daily at the University of Ottawa Heart Institute since April 2020 to triage all cardiac surgery referrals with a high degree of clinical success. The main objectives of our proposal are to systematically implement the CardiOttawa throughout Alberta and Ontario, and to evaluate clinical impact and the success of the implementation. We have partnered with clinicians and key policymakers and have developed a method for seamless integration at the provincial level. The care and outcomes of all patients requiring ICU resources may be substantially improved if clinical judgment is supported by objective quantification in the planning of care. The CardiOttawa will augment the clinician's ability to safely clear the surgical backlog and more efficiently allocate resources during the COVID-19 period and beyond.",2021,2023,Ottawa Heart Institute Research Corporation (Ontario),395000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health service delivery",2021 +C19819,202112FO1,Tajigoltieg - We are Healthy: Enhancing food security and mental wellbeing programs to manage COVID-19 pandemic stressors in a remote Mi'kmaq community,"Pandemic related stressors have presented an opportunity to address and mitigate the risks associated with food security and wellbeing programs in remote Indigenous communities. However, a significant gap remains regarding the development, evaluation, and updating of food security programs therein. Moreover, food security programs often lack in addressing Indigenous context within their plan guidelines. This program of research will evaluate and expand emergency food security and mental wellbeing programs in Miawpukek First Nation (MFN), under the guidance of the Health Director, Ada John. Our program of research has three objectives. First, to accelerate the development of wellbeing programming that connects food security, Indigenous Knowledge and wellbeing. Second, to evaluate the stress levels of residents in real-time to determine how impactful food asset initiatives and wellbeing interventions are while enduring a pandemic, and third, to assess how these recently acquired food assets contributed to food security, food sovereignty, and wellbeing during a pandemic and their potential as a long-term strategy within a remote First Nation community. The research program will implement traditional Indigenous food security practices and expand the existing MFN food asset initiatives to include health and wellbeing interventions to mitigate long and short-term pandemic-related stress. This would be achieved by accelerating the development of social programming that connects food security, co-designing the program using Two-Eyed Seeing practices, and evaluating the wellbeing (stress levels) of residents to determine the impact of food asset initiatives and wellbeing interventions while enduring a pandemic. Furthermore, we will also assess how these food assets contribute to long-term food security, food sovereignty, and wellbeing within a remote First Nation community by developing a best-practices framework for expansion to other communities.",2021,2022,Ryerson University,190796.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +C19820,202002OV3,Targeting genetic and chemical vulnerabilities of novel coronavirus SARS-CoV-2,"The recent outbreak of the SARS-CoV-2 coronavirus in China and its continued international spread threatens to become a global pandemic. Although coronaviruses generally cause mild respiratory infections in humans, over the past 18 years, three animal-derived coronaviruses have emerged that cause much more severe disease: SARS-CoV, MERS-CoV, and the current SARS-CoV-2. Each of these emergent viruses cause substantially higher death rates than common coronavirus infections; the current estimate of the death rate due to COVID-19 syndrome caused by SARS-CoV-2 infection is ~2.5%. The main challenge in addressing these new coronavirus-associated outbreaks is a lack of suitable therapeutics to treat active disease (i.e., anti-viral drugs) or to prevent disease (i.e., appropriate vaccines). We propose to apply genomics-based tools and drug-screening platforms to rapidly pinpoint new targets for SARS-CoV-2 anti-viral agents and to identify candidate therapeutic compounds. Our team has deep expertise in anti-infective drug discovery, the application of genomics in identifying drug targets, and in the biology and biochemistry of RNA viruses such as SARS-CoV-2. Our project will identify new therapeutic strategies that may help to treat COVID-19 patients. These strategies will also help mitigate newly emergent coronavirus-associated diseases that will undoubtedly continue to cause outbreaks in the future.",2020,2022,McMaster University,737028,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19821,202002OV3,Targeting programmed ribosomal frameshifting as a therapeutic strategy against 2019-nCoV,"The new coronavirus 2019-nCoV has spread rapidly in the last 3 months, infecting tens of thousands of people in dozens of countries and killing over 1,000, with no preventive vaccines or medications that can treat it. We propose to search for possible drugs to treat 2019-nCoV by targeting the ability of the virus to hijack the cell's machinery and recode how the genome is read via programmed ribosomal frameshifting (PRF). Coronaviruses use PRF, which is triggered by a specific structure (a 'pseudoknot') in the viral genome, to produce essential enzymes in specific ratios. Suppressing PRF in SARS coronavirus-which is very closely related to 2019-nCoV-disrupts viral propagation and significantly reduces infectivity, suggesting that PRF inhibitors could be used to combat 2019-nCoV. We will search for potential drugs that bind to the 2019-nCoV pseudoknot and disrupt PRF. We will first build a structural model of the pseudoknot by combining computational simulations with measurements revealing the base-pairing patterns and higher-order structures in the RNA. We will then use high-throughput computational tools to screen large libraries of existing approved drugs (which could be deployed rapidly), as well as publicly-available chemical compounds, for binding to the pseudoknot. Compounds predicted to have high binding affinity will be tested experimentally to confirm their binding-quantifying the binding affinity, identifying the binding site, and showing that binding alters the pseudoknot structural dynamics (thought to be important for triggering PRF)-and to measure their effectiveness at inhibiting PRF in cell extracts. We will examine if the effects of the compounds are specific to 2019-nCoV by repeating all measurements using other RNA structures as controls. Lead compounds will be passed on to collaborators for future studies assessing their effectiveness against live virus and suitability for deployment as therapeutics.",2020,2022,University of Alberta,222420,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C19822,202203MM1,Targeting the mitochondria in COVID-19 pneumonia: The cardiopulmonary effects of a SARS-CoV-2 mitochondriopathy,"COVID-19 is an acute respiratory illness caused by SARS-CoV-2. COVID-19 has caused > 223 million infections and >4.1 million deaths. Most infected people are mildly symptomatic; however, ~5% suffer respiratory failure requiring hospitalization and 1.5% die, usually of hypoxia (low blood oxygen) and lung injury. While vaccines offer hope, mutant viruses may evade vaccine protection and 20% of the population remain vaccine hesitant. COVID-19 is the third coronavirus to emerge in 20 years; and yet we lack understanding of coronavirus pneumonia or curative therapies. In 2020, we discovered that SARS-CoV-2 may worsen COVID-19 pneumonia by targeting mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC). Mitochondria are not just the powerhouse of the cell; they also control programmed cell death (apoptosis) and regulate hypoxia (hypoxic pulmonary vasoconstriction; HPV). SARS-CoV-2 damages mitochondria causing excessive AEC apoptosis and inhibiting HPV which worsens lung injury and hypoxemia. Our team has expertise in mitochondrial biology, SARS-CoV-2, virology, transcriptomics, synthetic chemistry, molecular imaging and disease pathogenesis. As part of a new collaboration with a SARS-CoV-2 expert at the Vaccine and Infectious Disease Organization (VIDO), we are testing the impact of replicating SARS-CoV-2 on mitochondria (structure/function/gene expression) in lung cells and assessing the effects of novel drugs that could treat COVID-19 mitochondriopathy in a SARS-CoV-2 hamster model. We also study conserved mechanisms of coronavirus cardiopulmonary toxicity using human (HCoV-OC43) and mouse (MHV-1) coronaviruses. Our in-silico drug discovery pipeline has identified new apoptosis inhibitors which, along with drugs repurposed to enhance HPV, we will test in two preclinical COVID-19 models. This research will identify the role of mitochondria in coronavirus pneumonia and create mitochondria-targeted therapies for COVID-19.",2022,2024,Queen's University,325155.6,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2022 +C19823,202111WI2,Telephone-Based Cognitive Behavioural Therapy for Post-Operative Bariatric Surgery Patients to Manage COVID-19 Pandemic Related Mental Health and Distress (TELE-BARICARE): A Randomized Controlled Trial to Determine Effectiveness and Adaptation for Marginalized Populations,"a type of ""talk therapy""] intervention focused on developing coping skills and specifically designed for weight loss surgery patients). Participants will complete measures of mental health distress, eating behaviours and a psychological distress scale prior to and immediately following the intervention. Implications: If Tele-CBT is found to improve post-pandemic mental health distress and eating behaviours, it could be routinely offered to patients with other chronic medical conditions as a resource to help manage psychological distress and mental health concerns emerging during and after the COVID-19 pandemic.",2021,2023,University Health Network,246113.44,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19824,202108VC1,Telling the Story: Gathering First Nations perspectives of COVID-19 Vaccine Deployment,"The First Nations Health Authority (FNHA) has been working alongside health system partners to respond to the COVID-19 pandemic since early 2020. In addition to managing pandemic response, First Nations leadership must attend to complex structural barriers to vaccine uptake and undertake strategies for building vaccine confidence. This research proposal seeks to fill a gap in data that incorporates First Nations ways of knowing as it applies to building vaccine confidence and consolidate effective strategies for increasing vaccination rates among First Nations individuals, families and communities. Informed by a Two-Eyed Seeing approach pairing Indigenous ways of knowing and research design with western behaviour change methods, this project will involve a scoping review, qualitative interviews, and focus group sessions with health care service providers, First Nations leadership and community members. Stories and knowledge gathered will be returned to the individuals and communities who are the rightful owners of that knowledge, and the study's findings will be shared with First Nations leadership to inform decision-making regarding COVID-19 vaccine uptake.",2021,2023,Simon Fraser University,150044.7,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C19825,202111WI1,Testing Resilience: An evaluation of the health system impact of COVID-19 in Post-Ebola Sierra Leone,"In 2014, Sierra Leone was hit with an unprecedented Ebola outbreak with devastating consequences for those directly affected by the virus and through collateral damage across other health sectors. Post-Ebola recovery plans were put into place centered around strengthening systems-level resiliency to buffer against structural shocks like future pandemics. When COVID-19 hit the country in 2020, this post-Ebola health system strengthening was tested. Our team, a partnership between scientists Sierra Leone and Canada, proposes to examine the wider impacts of the COVID-19 pandemic on essential health services in Sierra Leone. First, we will measure the extent to which the COVID-19 epidemic changed the delivery/uptake of essential services and led to negative health outcomes in infectious diseases (HIV, tuberculosis, malaria), childhood vaccination, maternal health. We will compare this wider health impact against that of the Ebola epidemic. Second, we will examine how differences in public health measures and SARS-CoV-2 vaccine coverage over time and geography (districts) influenced service disruption, and the extent to which adaptive service reconfiguration (adaptations and enhancements) may have mitigated the wider health impacts of the COVID pandemic. Results will be used by stakeholders and service providers, including the National COVID-19 Emergency Operations Center and the Sierra Leone Ministry of Health and Sanitation, to inform ongoing program adaptation in the context of future waves of COVID in a region with limited SARS-CoV-2 vaccine supply to date.",2021,2023,Unity Health Toronto,394894.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Africa,Africa,,,,Sierra Leone,Sierra Leone,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19826,202109EG2,"The Canadian Surveillance of COVID-19 in Pregnancy: Epidemiology, Maternal and Infant Outcomes","Towards the goal of understanding the burden of COVID-19 on pregnancy, the Canadian Surveillance of COVID-19 in Pregnancy: Epidemiology, Maternal and Infant Outcomes (CANCOVID-Preg) was initiated. CANCOVID-preg is a national surveillance project that tracks all pregnant cases with documented SARS-CoV-2 infection. To date, our team has developed four reports outlining preliminary Canadian data from a subset of provinces. Results indicate that pregnant persons are at increased risk of severe illness related to COVID-19. These reports were, in turn, used by public health officials in the decision to prioritize pregnant populations for vaccination in Canada and informed three statements on COVID-19 in pregnancy published by the Society of Obstetricians and Gynaecologists of Canada. Despite public health recommendations, high rates of vaccine hesitancy exist among pregnant persons. Additionally, a proportion of fully vaccinated individuals are now developing symptomatic, or asymptomatic, COVID-19 breakthrough infections. With lower vaccination rates, and the occurrence of breakthrough infections, the need to understand variant transmission and severity over time, in vaccinated and unvaccinated, pregnant populations has become a crucial next step in the rapidly evolving pandemic. By directly addressing the health of this underserved population, CANCOVID-Preg meets the Differential Impacts of COVID-19 on Historically Excluded or Underserved Populations research area. This project also meets both CIHR objectives by leveraging CANCOVID-Preg's existing surveillance network and real-time evidence to optimize Canada's pandemic response, thereby mitigating the negative consequences of COVID-19 for both new mothers and their infants.",2021,2022,University of British Columbia,394936.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics | Disease susceptibility,2021 +C19827,202005VR4,"The COVID-19 Hospital Analytics Laboratory: Improving the Clinical, Organizational, and System Response to COVID-19","Hospital care has been dramatically reorganized to respond to the COVID-19 pandemic, with an urgent need to preserve scarce resources like ventilators and personal protective equipment. Yet, there is minimal evidence about how to care for patients with COVID-19 in hospital and how to maintain high quality non-COVID care during the pandemic. Detailed clinical data, such as patient vital signs or medications, are needed to study COVID-19 and its individual- and system-wide effects. These data are available in hospital computer systems but have not been widely collected and shared for research. The General Medicine Inpatient Initiative (GEMINI) has collected detailed clinical data from >340,000 admissions at 7 hospitals in Ontario, making it the largest inpatient repository about adult medicine in Canada and a valuable data source to study COVID-19. We propose to create the COVID-19 Hospital Analytics Laboratory by extending GEMINI to the 30 largest hospitals in Ontario, representing 70% of acute medical/ICU beds in the province. We will collect detailed clinical data from all medical and ICU admissions, including COVID-19 and other medical illnesses. Data will be linked to ICES longitudinal population datasets and updated every 1-3 months to create a globally unique platform that enables advanced analytics and machine learning and includes a diverse sample of patients, meaning research insights will be widely applicable. This platform will address all 5 CIHR objectives by supporting a breadth of research focused on improving hospital care in the setting of COVID-19. Data will be accessible to global experts in artificial intelligence, operations engineering, population modeling, public health and clinical epidemiology. Our first two research priorities will be to improve understanding and prediction of clinical outcomes in patients hospitalized with COVID-19 and to study how the organization of hospital care in the setting of COVID-19 affects patient outcomes.",2020,2021,Unity Health Toronto,1507875,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Prognostic factors for disease severity | Supportive care, processes of care and management | Health service delivery",2020 +C19828,202005VR4,"The COVID-19 Ontario Pregnancy Event (COPE) Network: Assessing the impact of COVID-19 in pregnancy on maternal, fetal and newborn health","Data collection and research on COVID-19 in pregnancy are urgently needed to fill the many knowledge gaps about the impact of COVID-19 on maternal, fetal and newborn health. We propose to leverage Ontario's birth registry, and the COVID-19 Ontario Pregnancy Event (COPE) Network - a collaboration of 12 obstetrical hospitals in 5 of Ontario's largest cities - to launch a series of seroprevalence, vertical transmission and surveillance investigations that will generate rapid, rigourous evidence on the impacts of COVID-19 in pregnancy. We will achieve this by (1) implementing universal screening of all pregnant women to assess the prevalence of symptomatic and asymptomatic SARS-CoV-2 infection; (2) generating complete infection and antibody profiles of maternal and newborn tissues to assess the mother-to-infant transmission potential of SARS-CoV-2 among mothers affected by COVID-19; and (3) generating in-depth obstetrical profiles of pregnancies affected by COVID-19 to assess clinical characteristics, case management and maternal and neonatal outcomes associated with infection during pregnancy. Our multi-disciplinary, high-qualified team has an established track-record in pregnancy and birth cohorts, molecular virology and infectious diseases, and are well-positioned to fulfill these objectives. Our findings will inform strategies to optimize processes in care, patient counselling and health systems management specific to the obstetrical and neonatal population, and will lay the foundation for follow-up studies to assess the longer-term health implications of COVID-19 on infant health. The relevance of our findings will not be limited to Ontario but will be of value to clinicians and families across Canada and globally.",2020,2021,Ottawa Hospital Research Institute,596669.25,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease transmission dynamics | Prognostic factors for disease severity,2020 +C19829,202005VR5,"The COVID-19 Pandemic Among Sexual and Gender Marginalized Populations in Canada: Physical Distancing Impacts, SARS-CoV-2 Seroprevalence, and Health and Wellness Needs","Physical distancing may have especially negative effects on marginalized communities such as lesbian, gay, bisexual, trans, queer, Two-Spirit, and other sexual and gender marginalized people (LGBTQ2+). LGBTQ2+ people are more networked socially and sexually compared with other groups. LGBTQ2+ also experience other health inequities such as cardiovascular disease, poorer mental health, and more substance use that may result in greater COVID-19 impacts. This study will determine how COVID-19 impacts LGBTQ2+ people across Canada. We will conduct an online survey of LGBTQ2+ people. Our findings will inform future public health action for LGBTQ2+ people to avoid unintended consequences such as intimate partner and family/domestic violence, anxiety, and depression. Participants will also be mailed a kit to collect a few blood drops to test for COVID-19. This approach may be an important tool for future COVID-19 testing, especially among rural, remote, and Indigenous communities.",2020,2021,University of Victoria,0,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts,2020 +C19830,202107UIP,The COVID-19 pandemic and its longitudinal associations with youth's mental health: Examining risk and protective factors,"In response to the ongoing COVID-19 pandemic, the Canadian government implemented several restrictive measures since March 2020 to decrease social contacts and increase physical distance. Although these measures were necessary to limit the transmission of the virus, there are reasons to be concerned about their impact on the adolescents, who are probably the group with the greatest need to socialize with their peers. In fact, it may have been more difficult for adolescents during the pandemic to have their first romantic relationships, to be involved in schools or get a job. Some youth may be even more vulnerable to the effects of the pandemic, namely, those having experienced prior adverse life events such as child maltreatment or bullying, and adolescents belonging to a sexual and gender minority (LGBTQ2+). Indeed, independent of the pandemic, these two groups tend to experience greater rates of stigma, social isolation, and mental health issues compared to their non-victimized, non-minoritized peers. Moreover, as the pandemic deprived them of the majority of extra-familial supports and/or programs, it may have been more difficult for these adolescents to cope. The proposed research will examine the effects of child maltreatment and bullying on youth's mental health in the aftermath of the pandemic (e.g., COVID-related stress, post-traumatic stress symptoms, anxiety/depression, alcohol and drug) and the impacts of support and extra-curricular activities on their well-being. We will also examine these outcomes among sexual and gender minority youth. This study will document the progression of mental health among 3,900 adolescents, before (school year 2019-2020), during (school year 2020-2021) and after (school year 2021-2022, present proposal) the COVID-19 pandemic. Findings will inform the development of targeted interventions to better help adolescents, and high-risk groups therein, as well as mitigate the long-term impacts of this unique global challenge.",2021,2022,Université du Québec à Chicoutimi,118467.61,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts,2021 +C19831,202111WI2,"The COVID-R3ICSAB Study: COVID-19 Wide Impact: Research on the Risk and Resilience In Special Communities of Chinese, South Asian and Black Populations","COVID-19 has disproportionately affected visible minorities in the population, with increased mortality, and major health and socioeconomic consequences with disruptions. Unfortunately most of this information comes from data in the US and UK, as surprisingly Canada has NOT been systematically collecting race based health data! Our COVID-R3ISCSAB team attempted to address this critical knowledge gap in Canada by analyzing COVID-19 health data with previously validated surname algorithm to assign race, and published the analysis for Chinese and South Asian populations with increased death and complications in Ontario. By lobbying governments, the race/ethnicity information is now included in the 2021 Ontario and Alberta health data. Using this new tool, we aim to identify the impact of COVID-19 on racial communities during the 3rd wave and now post-recovery in Ontario and Alberta. We will also analyze the delay in cardiovascular care because of the pandemic, and the impact of Long Covid on the racial minority populations, in comparison to majority white population. Armed with accurate race data and associated risks, we will engage the Chinese, South Asian and Black individual communities, including the medical leaders, community networks and patients, to formulate community specific solutions, gaining in depth insights, to mitigate future COVID waves and emerging pandemics. We will simultaneously work closely with our knowledge mobilization teams, including Public Health and Ministry of Health leadership, together with community leaders and members. This will enhance the resilience of the population, and help to establish a community based Pandemic SWAT team to address future waves and pandemics.",2021,2023,Ottawa Heart Institute Research Corporation (Ontario),393585.9,Human Populations,Asian | Black,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2021 +C19832,202107UIP,"The economic and social impact of eating disorders in youth across Canada: how much did the COVID-19 pandemic cost youth, families, and the system?","The restrictions that came with the COVID-19 crisis resulted in a striking increase in rates of eating disorders among Canadian children and youth, affecting families and caregivers alike. Unfortunately, the eating disorder system of care was unprepared for this large increase in cases and needs, leaving many unable to access help when they most needed it. The system was mostly unprepared as it did not have a good sense of how many youth needed help both before the pandemic, and then during, so that we could assign and use our scarce resources appropriately. To better prepare the eating disorder system going forward and to understand how the pandemic shifted things, this study will use different approaches to better understand the prevalence, social and economic costs related to the impact of COVID-19 on eating disorders in children, youth and families in Canada. Comparing national and province-specific rates pre-pandemic (2019) and during (2020) will allow for a deep understanding of how the restrictions affected those with eating disorders from across Canada. Following the same process used in costing analyses done in Australia and the US, this project plans to ask the same health economy firm (Deloitte) to assist with a similar costing analysis in Canada. To complement this work, a scoping review of prevalence studies of eating disorders in Canada will also be done along with interviews with a variety of individuals from each province to help understand how the pandemic may have affected individuals differently based on region and imposed public health measures. Findings from this study will help policy-makers and healthcare leaders better understand how the pandemic affected individuals and their families with eating disorders across Canada, and provide important estimates to improve the eating disorder system of care for post-COVID recovery efforts.",2021,2022,Children's Hospital of Eastern Ontario Research Institute Inc,118472.35,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19833,202109EG2,The effects of school and childcare participation during the COVID-19 pandemic on young children and their parents: the TARGet Kids! Study of Children and Families,"Children have been underrepresented in COVID-19 research due to the low risk of becoming severely ill from the SARS-CoV-2 infection. However, the effects of COVID-19 public health measures such as school and childcare closures on Canadian children are potentially more severe and far-reaching than the infection itself. Research is needed to understand and monitor the ongoing impact of school participation and childcare attendance on multiple domains of health and well-being of children and their parents. We propose to use the TARGet Kids! longitudinal cohort study of Children and Families, with data already collected pre-pandemic and since April 2020 to understand the impact of school participation and childcare attendance on health and developmental outcomes of children and their parents, including their health behaviours, education, development, weight change, and health, developmental, and community services utilization over time in young children age 0-12 years and their parents in the Greater Toronto Area. We also plan to understand the roles parental stress and socio-demographic factors play in these relationships. With repeated data collected before the pandemic and during the first 1.5 years of the pandemic and detailed socio-demographic data collected from a diverse population (one in three children participating in the TARGet Kids! COVID-19 Study are ethnic minorities), we plan to continue to collect repeated data on multiple domains of child and parent health over the next year to evaluate the long-term effects of COVID-19 public health measures on Canadian children and their families. Real-time data from a diverse children population are crucial to guide the planning and delivery of mitigation strategies to support the recovery for children and their families from the COVID-19 pandemic.",2021,2022,Hospital for Sick Children (Toronto),394845.95,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts | Social impacts,2021 +C19834,202111WI3,"The EMPOwer (Equitable Mental wellness Programming for Older Adults with multiple chronic conditions ) - An RCT to assess the impact of scalable, effective online solutions","Drastic social changes during COVID-19 have had a significant impact on the lives of older adults (aged 55+ years) with multiple chronic conditions. This group is at high risk of worsening mental health and social isolation. Online mental wellness programming is ideal for broad dissemination, but needs to be carefully designed to ensure it serves the unique technology, engagement and content needs of this group. Working together with patients, we have designed an evidence-based, 12-week online mental wellness program. Usable by older adults from tech novices to experts, the program includes physical movement at 4 levels, and a psychology informed chronic disease behavioural skills series. In our effectiveness work, the program has shown 90% completion rates and significant improvements in anxiety, depression and resilience. To date, it has been provided alongside costly 15-minute weekly 1-to-1 phone check-ins. With a vision of scaling the program broadly, alongside a team of patient Partner organizations, we propose to assess the effectiveness of two new features introduced to replace the weekly check-ins: gamification and live online group classes. 500 participants aged 55+ years with 2 or more chronic conditions will be randomized to a study group: (1) mental wellness program (control), (2) mental wellness program + gamification, or (3) mental wellness program + gamification + group classes. The primary study outcome measure is change in anxiety and depression scores after 12 weeks. Secondary study outcomes include changes in loneliness, social isolation, resilience, quality of life, sleep quality, adherence, and acceptability of the program. This adequately powered trial will provide data on a co-developed program that can be distributed by Partner organizations to their patients, guide relevant policy and service revisions to reflect mental health supports of older adults using digital technology, and enhance our understanding of the pandemic's impact.",2021,2023,University of Alberta,661936.26,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19835,202107UIP,The expansion of a parent-focused physical literacy intervention for early childhood called PLAYshop,"COVID-19 restrictions have increased childhood physical inactivity putting many children at risk for sub-optimal development. The PLAYshop program, a novel, brief, theory-based, parent-focused physical literacy intervention, can support families to help mitigate this major public health issue. Our previous work, in higher socioeconomic status families, found improvements in parental outcomes to promote children's physical literacy development or their ""capacity for a physically active lifestyle"". In partnership with knowledge users, we will examine if the PLAYshop program increases parental confidence, knowledge, and perceived availability of resources to support preschool-aged children's physical literacy development in families of lower socioeconomic status. We will also examine the PLAYshop program implementation. We will enroll 130 parents of preschool-aged children (3-5 years) among families classified as low income. The intervention group will receive a virtual workshop, a goody bag of resources/equipment, access to an online toolkit, and booster emails/texts. The waitlist control group will receive the same PLAYshop program at a later date. Parental variables will be measured with baseline and follow-up surveys. We will use statistical tests to determine if these variables are larger at follow-up in the intervention group compared to the control group, taking into account baseline values. We will explore implementation facilitators and barriers using telephone interviews with parents at 2-month follow-up and with workshop leaders at the end of the study. We will identify themes across these interviews. The PLAYshop program has the potential for meaningful benefits during and post COVID-19. Study findings will be informative for our large network of knowledge users who are interested in supporting the expansion of the PLAYshop program. Additionally, findings will inform future collaborations regarding an adapted PLAYshop program in Indigenous communities.",2021,2022,University of Alberta,118500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19836,202111WI1,The impact of COVID-19 and related control measures on the hepatitis C virus care cascade,"Measures taken to limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission have limited access to healthcare services worldwide. Declining testing volumes, diagnosis and treatment rates for blood-borne infections such as hepatitis C virus (HCV) were reported in England during early phases of the coronavirus disease 2019 (COVID-19) pandemic, showing significant disruptions in healthcare provision for these illnesses. These disruptions may have long-term implications for people who already face barriers to accessing care and are at increased risk of infection, complications and death, including people who inject drugs (PWID), who are also affected by the ongoing opioid overdose crisis; gay, bisexual, and other men who have sex with men (gbMSM); immigrants; and incarcerated persons. HCV care cascades can identify gaps in healthcare service provision along the HCV care journey, including: (i)antibody diagnosis, (ii)ribonucleic acid (RNA) testing, (iii)RNA positive diagnosis, (iv)genotyping, (v)treatment and (vi)cure. Large declines in HCV testing and diagnosis rates were reported in British Columbia (BC) and Ontario (ON) at the start of the pandemic, however comprehensive data on the full care cascade are currently unavailable. Data is also lacking on pandemic related changes in HCV care in other Canadian provinces, which are needed to assess and mitigate the effect of the pandemic impacts on the health of people living with HCV in Canada, especially among priority populations. Using testing and administrative data from BC and ON, this project aims to assess the impact of the COVID-19 pandemic and related control measures on (i)HCV care cascades in BC and ON; and (ii)HCV reinfection and death among PWID, gbMSM and immigrants. Surveys conducted among people from priority populations listed above and among healthcare providers will complement care cascade data and provide details on, and practical solutions to, on-the-ground impacts of the pandemic.",2021,2023,University of British Columbia,392882.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Internally Displaced and Migrants | Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19837,202112FO1,The impact of COVID-19 on the care and outcomes of off-reserve Indigenous older adults living in long-term care and receiving home care,"Most COVID-19 deaths were among vulnerable older adults living in long-term care (LTC) homes. This has led to calls for improvements in the quality of care provided in LTC homes. While the overall number of cases and deaths in LTC homes is well-documented, little is known about how COVID-19 had affected Indigenous residents in LTC. This includes a lack of information about the lasting impacts of COVID-19 (i.e., long COVID) on both Indigenous and non-Indigenous LTC residents. Similarly, those receiving publicly funded home care have been found to be more vulnerable to COVID-19. One study conducted in Ontario before the pandemic found that Indigenous older adults receiving home care in Ontario had poorer health outcomes compared to non-Indigenous older adults receiving home care. Again, little is known about COVID-19 infection rates and outcomes for home care recipients. The current study will use health data to 1) describe and compare the socio-demographic and health status profiles of Indigenous and non-Indigenous LTC residents and home care recipients; 2) evaluate the quality of care received by Indigenous and non-Indigenous LTC residents and home care recipients during the COVID-19 pandemic; 3) measure and compare COVID-19 outcomes among Indigenous and non-Indigenous LTC residents and home care recipients; and 4) identify what factors are associated with COVID-19 outcomes for Indigenous older adults. Understanding COVID-19 infection rates and outcomes among Indigenous LTC residents and home care recipients is important to support efforts to achieve equitable care and health outcomes. The findings of the study will allow for conclusions to be drawn about how to decrease the negative impacts of the COVID-19 pandemic in these settings.",2021,2022,University of Ottawa,197488.94,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Indigenous People | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts | Health service delivery,2021 +C19838,202111WI1,The Impact of COVID-19 on the Diagnosis and Treatment of Breast Cancer (TICTOC): a population-based study,"INTRODUCTION: During the COVID-19 pandemic, there were limitations in healthcare resources which led to restricted access to breast cancer screening and treatment. These limitations have the potential to further exacerbate pre-existing disparities in breast cancer care. METHODS: We will use linked healthcare administrative databases in Ontario to assess for regional variations in breast cancer screening and treatment. We will also explore breast cancer care during the pandemic for marginalized patients. Lastly, we will determine the impact of virtual care and virtual multidisciplinary cancer conferences on breast cancer care during the pandemic. SIGNIFICANCE: This study will the first population-based study in Canada to describe patterns of breast cancer screening and treatment during the pandemic between regions and among marginalized populations. Results from this study will help inform future research and policies on breast cancer care after the pandemic.",2021,2023,University Health Network,234566.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19839,202112FO1,The impact of COVID-19 on vaccine uptake and immunization rates for First Nations people in Alberta,"COVID-19 has negatively impacted Indigenous communities more than others. Ongoing social, racial and systemic inequities due to colonialism have compounded with government and public health measures in response to COVID-19. While there are effective vaccines to prevent and lower COVID-19 infections, Indigenous peoples have a long and painful history with disease outbreaks, with western medicine and healthcare, including vaccines. To date, we do not know how Indigenous peoples are accepting COVID-19 vaccines and the pandemic's influence on other routine immunizations. Using the existing Community Health Immunization Program (CHIP) and Alberta Health data, we will work with First Nations communities to report COVID-19 and other immunization data for First Nations and Urban Indigenous peoples in Alberta. This includes real-time COVID-19 immunization rates, as well as other routine immunization patterns for adults and children before, during and after COVID-19 waves. Also, we will document any cultural-specific practices used to promote COVID-19 vaccination, to be shared and used to shape future immunization programming for First Nations and Urban Indigenous communities. Our study examining COVID-19 and other immunizations in First Nations people is timely and important. This work will allow First Nations communities to better understand COVID-19 vaccine acceptance and how COVID-19 is influencing routine immunization programs. Taken together, this work will assist in COVID-19 response and immunization program planning post-pandemic for Indigenous people across Canada. Our strong partnerships with First Nations communities and use of existing data platform (CHIP) will enable the co-design, co-creation of materials, and use of the findings to inform current and future immunization program planning. We will build awareness and share results together.",2021,2022,University of Alberta,197500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2021 +C19840,202111WI2,The impact of COVID-19 physical distancing restrictions on the health and wellness of long-term care residents in Ontario,"Globally, the COVID-19 pandemic has had an indescribable impact on daily life. In many regions, long-term care (LTC) homes felt the brunt of this impact, experiencing high rates of infection and mortality among their residents. As the system grappled with increasing infections and resulting deaths, many jurisdictions, including Ontario, vowed to put an ""iron ring"" around the LTC system, implementing a number of physical distancing measures, including an end to in-person visitation. While the restrictions sought to reduce SARS-CoV-2 transmission, it is unclear what secondary impacts or unintended consequences the restrictions have had on individuals living in LTC. This project will combine important contextual information gathered through surveys of LTC homes with comprehensive administrative health data to better understand the impact of different approaches used to meet public health guidelines to ensure physical distancing. Specifically, we are interested in understanding if some restrictions were more effective at reducing the spread of infection than others, and if these restrictions had a detrimental effect on resident health and wellness. Our mixed methods study also includes interviews with patients, families, and caregivers to explore and understand their experiences with long-term care both before and during COVID-19 restrictions, focusing on the nature and extent of the physical distancing restrictions and deliberative dialogues with key stakeholders including LTC providers and administrators, provincial government and public health representatives, and patients and caregivers. Overall, the goal of this work is to provide actionable recommendations to optimize social contact among LTC residents while minimizing the risk of infection. The findings of this study are critical for local, provincial, and national policy makers to consider as we continue to deal with the ongoing spread of COVID-19 and prepare for future pandemics.",2021,2023,Queen's University,371831.67,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts,2021 +C19841,202111WI2,The Impact of Olfactory Dysfunction on Social and Mental Health,"An estimated one million Canadians have experienced olfactory dysfunction associated with COVID-19 in the past 18 months. Though typically short-lived, a substantial minority COVID-19 patients report long-lasting olfactory problems. Olfactory dysfunction is related to a range of social and emotional impairments, including elevated rates of depression, anxiety, social isolation, and relationship difficulties. Although these links are well documented, we know relatively little about why and how these problems are linked. Our first aim is to capitalize on this rare opportunity to examine the pathways linking olfactory loss to social and emotional problems. We will recruit adults online reporting recent onset of olfactory dysfunction and no other flu-like symptoms (N=300) as well as a control cohort (N=100). Participants will monitor their olfactory ability, social interactions, and mental health for 8 weeks, covering the typical period of olfactory recovery in COVID-19 patients. These data will provide a first-ever look at how within-person changes in olfaction relate to changes in social behavior and emotional wellbeing. Moreover, given that COVID-19 associated smell disorders are likely to exist for many years to come as this illness becomes endemic, mitigating the impacts of olfactory dysfunction is an emerging health priority. Our second aim is to develop a brief, scalable, online intervention to mitigate the emotional and social consequences of olfactory loss. We will conduct a randomized pilot trial on a subset of participants (n=100) who receive two tailored 3-week behavioral interventions focused on bolstering social support and mitigating social avoidance. Patient engagement and satisfaction will inform intervention refinement, with the eventual goal of offering the web modules freely and publicly. Our findings will inform future efforts to improve mental health for people with olfactory dysfunctions, including those dealing with sudden onset due to COVID-19.",2021,2023,University of Victoria,333046.62,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management | Indirect health impacts",2021 +C19842,202107UIP,The impact of the COVID-19 pandemic on the mental health of children and youth,"Emergency measures aimed at reducing the spread of COVID-19 have unsettled all aspects of the lives of Canadian children and youth. In Ontario, home to close to 40% of Canadian children and youth, school closures and stay-at-home orders have produced prolonged periods of social and physical isolation from classmates and extended family. Simultaneous disruptions in the availability of extracurricular activities and access to health care and specialized support services further increased the isolating effects of the COVID-19 pandemic, predisposing children and youth to worsening mental health. However, there is limited research describing the impact of COVID-19-related public health measures on the mental health of children and youth. This is especially important for disadvantaged children and youth for whom the harmful effects of emergency measures may be worsened by pre-existing disadvantage, such as lack of internet access for remote learning or medical appointments, poverty, and living in neighbourhoods without parks or green space. Our goal is to understand the impact of the COVID-19 pandemic and associated restrictions (e.g., lockdowns, school closures) on the mental health of children and youth in Ontario. We will specifically study hospital admissions and emergency department visits for mental health conditions, emergency department visits for self-harm, and prescriptions for psychotropics (i.e., antidepressants, benzodiazepines, stimulants and antipsychotics). For each of these outcomes, we will study how their occurrence changed with COVID-19, whether there were differences according to the neighbourhood of residence, and the relationship with the duration of lockdowns and school closures. We will also study whether there were differences between females and males, by age group, between children and youth with and without mental health or neurodevelopmental conditions before the pandemic, and according to features of the neighbourhoods of residence.",2021,2022,Unity Health Toronto,118376.76,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19843,202111WI1,The indirect impact of COVID-19 on cardiac function and associated outcomes in patients awaiting cardiac surgery: An opportunity to inform data-driven surgical wait list management,"During the COVID-19 pandemic, non-urgent surgeries, including many heart surgeries, were delayed to free up hospital staff and space to care for patients with COVID-19. However, waiting for heart surgery can cause permanent damage to the heart, which may impact a patient's long-term health and survival. We do not know the impact of pandemic-related delays in heart surgery on a person's heart function or longer-term health. We also do not know whether some people are especially at risk of deteriorating while waiting for heart surgery. Even before the pandemic, some groups of patients, such as women or people from poorer neighbourhoods, had long wait times for heart surgery, leading to poorer health after surgery. The pandemic may have made this trend even worse. Together, this information will be important in understanding which patients on the heart surgery waiting list should be prioritized. We will study the indirect impact of the COVID-19 pandemic on heart surgery patients at 2 hospitals in Ontario. Specifically, we will examine heart function and long-term health in 8,000 patients waiting for heart surgery in the 2 years before and the 2 years during the pandemic. Our first goal is to examine the effect of the pandemic on wait times, heart function, and long-term health in heart surgery patients. Our second goal is to identify factors (e.g., sex, income level, surgery wait time) that predict which patients will experience a decline in heart function and poor long-term health as a result of waiting for heart surgery. Because it will take many years to clear the backlog of heart surgeries caused by the COVID-19 pandemic, it is important to understand whose heart function is most likely to decline while they are on the surgery wait list. These patients should be prioritized for surgery to prevent poor long-term health. This approach could lead to better and fairer wait list policies both during and after the pandemic.",2021,2023,University Health Network,324789.54,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19844,202109EG2,The landscape of risk: examining the correlates of inequitable COVID-19 infection and vaccination rates in Manitoba using population-based laboratory and administrative healthcare data,"COVID-19 has disproportionately impacted the most vulnerable segments of our society, those with chronic conditions, those impacted by substance use, those with intellectual disabilities, and those at sexually transmitted and bloodborne infections. This study will use population-based COVID-19 testing data linked to other sources of routinely collected data, like doctor visits, hospitalizations, and prescription drug fills to understand how things like age, where you live, and the characteristics of your neighbourhood contribute your risk of getting COVID-19 if you belonged to one of these groups. We will also examine vaccination rates within these groups, and also examine some factors that might be associated with vaccination. We will also plan on looking at factors that might be associated with people getting COVID-19 even after vaccination. The results from our study will be used to help prioritize care, including future vaccination efforts in those that have the most trouble accessing vaccines.",2021,2022,University of Manitoba,189554.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience",Immunity | Disease susceptibility | Prognostic factors for disease severity | Approaches to public health interventions,2021 +C19845,202111WI1,The long and short of disruptions in surgical services due to the COVID-19 response: the impact and path forward,"Hard decisions were made about healthcare delivery in response to COVID, largely without evidence due to the unprecedented and rapidly evolving nature of the pandemic. Non-urgent surgeries were delayed to create space for the surge of COVID patients. The implications of these decisions are beginning to become clear and are widespread. Decision-makers want and need evidence to decide how to redesign surgical services to manage the backlog of surgical cases and to plan for additional waves of COVID-19 and subsequent pandemics. We will generate evidence to support decisions about surgical services during COVID and other pandemics by answering 3 questions: 1) How do pandemics affect surgical care delivery? We will conduct an environmental scan of major surgical centres nationally to understand surgical service reallocated across Canada. 2) What is the impact of delaying non-urgent surgeries on surgery patients, healthcare providers and the healthcare system? We will extend our current work examining the impact of the first wave of COVID-19 on surgical care using administrative/clinical databases to include the subsequent waves, and we will conduct interviews with patients whose scheduled surgery were delayed and their healthcare providers to understand the impact of delaying non-urgent surgeries. 3) How can we design surgical services in the future? Canadian decision-makers will use our findings to discuss and begin to establish guidance for surgical service provision during COVID and future pandemics, including managing a backlog of surgeries using a World Cafe. We have strategically assembled a national team of researchers, clinicians, and decision-makers (knowledge users) to generate user-driven evidence to inform the provision of surgical care during COVID-19 and future public health emergencies. Our findings will directly influence a redesign of surgical service delivery within our ""new normal"" healthcare system and for the future.",2021,2023,University of Calgary,198856.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19846,202111WI1,The McGill Task Force on the Impact of COVID-19 on Cancer Control and Care: Generating Evidence and Developing Strategies to Mitigate Future Cancer Risk for Canadians,"The COVID-19 pandemic caused major disruptions to cancer control and care services in Canada. Patients with cancer are at a particularly high risk of negative outcomes from delays in diagnosis and treatment. Our objective is to examine the impact of the COVID-19 pandemic on cancer prevention and care in Canada, and estimate its long-term impacts on cancer mortality and socioeconomic health inequalities. For this research project, we will: 1. Estimate at the population level the short- and long- term impacts of the pandemic on site-specific adult cancer care trajectories using Quebec administrative health databases. We will use medical claims, hospital records, and death registry data for approximately 1,000,000 cancer patients diagnosed between 2010-2026 to assess the impact of the pandemic on cancer incidence, treatment pathways, and cancer survival in adults. 2. Expand a decision model of cancer epidemiology in Canada to include data on cancer incidence and mortality by socioeconomic status and ethnic identity. We will use this model to predict the long-term impacts of the pandemic on cancer health inequalities in Canada. 3. Update our review of Canadian cancer-related clinical practice guidelines to include pandemic recovery efforts across the cancer care system. Previously, we found that the cancer care system had quickly responded to the first pandemic wave by publishing guidelines for cancer treatment and prioritization during the pandemic. For this update, we will specially focus on how the healthcare system has implemented recovery efforts across the cancer care spectrum, including resumption of cancer screening and preventive services. Our research will provide quick evidence needed to inform cancer care recovery efforts in Canada, and assess whether directives put in place to protect cancer care delivery during the pandemic have been effective at mitigating long-term negative impacts on cancer outcomes.",2021,2023,McGill University,394336.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19847,202111WI1,The Next Steps for Childhood Vaccination: Community and Expert Consultation in Addressing Reductions in Childhood Vaccination Access and Uptake Amidst the COVID-19 Pandemic for Kids New to Canada,"The COVID-19 pandemic has changed children's formative years, including their schooling, social opportunities, and health. Routine childhood vaccinations (RCVs) protect children against life-changing illnesses. Kids new to Canada often have incomplete vaccinations as RCV is not part of routine immigration medical examination, the Canadian schedule differs from the WHO schedule, and documentation practices vary. Combined with recent reductions in access to primary care clinics, pharmacies, and schools, these factors may put this group at higher risk of not having access to or not wanting RCVs. We aim to examine this pandemic's effects on access to RCVs, attitudes about RCVs, and vaccination-seeking behaviours-specifically for kids new to Canada (in the past five years). Our study will have three components: 1.Environmental scan and scoping review: examining current knowledge of how the pandemic has affected RCV uptake, access, knowledge, and attitudes. This will also include interventions that jurisdictions have begun to implement to address these gaps. 2.Primary data collection: surveys, focus groups, and interviews involving key stakeholders (newcomers, public health, school boards, community organizations) to understand how the pandemic has affected RCV uptake, knowledge, and attitudes. We will also utilize administrative data. 3.Identifying potential interventions: we will identify potential interventions to improve RCV uptake in conjunction with discussion with stakeholders so that they may implement them alongside governmental organizations. Getting this population on track with RCVs will require strategies that are practical and agreeable to those impacted by them. The process of creating these plans will ensure fairness in the planned projects, the behavioural changes sought, and the goals of improved public health. We expect that this process will help to determine what types of interventions may be most beneficial now and in future public health crises.",2021,2022,University of Calgary,196176.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Policy research and interventions,2021 +C19848,202002OV6,The Paradox of Precaution: Examining Public Health COVID-19 Outbreak Management Strategies,"In any outbreak, public health focuses on surveillance, containment, and providing recommendations for how the public can stay safe: wash hands, cover coughs, stay home when sick, and get vaccinated if one is available. While this is similar messaging to what is heard in cold/flu season, what separates these events apart is the inherent uncertainty involved during the emergence of a novel virus. However, when public health best practice (e.g. quarantining returning nationals from Wuhan) is attacked as putting people in ""medical jails"", or when the WHO implores governments for emergency resources to manage the outbreak by declaring the novel virus as ""public enemy number one"" akin to a ""global threat potentially worse than terrorism"", it creates a paradox around the concept of precaution. There is an urgent need to examine the cultural, social and political responses to the management of the current outbreak in real time. The objectives of this research are: 1) to evaluate how cautionary public health messages for the outbreak are presented by the news media; 2) to evaluate whether public health agencies are using social media and how well these tools, if used, increase public understanding of these outbreaks; 3) to assess how members of the general public, including special targeted groups, understand the outbreak, both the risks of disease and the risks of contraction; 4) to evaluate how effectively members of the public feel they can protect themselves given public health outbreak communication, and how they make sense of this relative to seasonal influenza risk messaging; and 5) to assess public response to a novel vaccine if one becomes available. We will meet these objectives through a content analysis of news media stories / social media, and interviews with public health communication leads (objs 1&2) and focus groups/surveys with members of the general public and targeted communities (e.g. Indigenous peoples, Asians) in select Canadian cities (objs 3-5).",2020,2022,University of Manitoba,374798.25,Human Populations,Asian | Other,Adults (18 and older),Unspecified,Indigenous People | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C19849,202203MM1,The prospect of wise governments: The Canadian experience of policy learning in and after COVID-19 pandemic,"The COVID-19 pandemic underlines the importance of global health issues and the important role that public authorities at all levels of government must play to detect and contain the outbreak. Despite numerous efforts to improve health systems in Canada, these systems are ill or insufficiently prepared to face challenges such as COVID-19. Our research project looks at short and mid-term strategies used by provincial and federal governments in Canada to deal with the pandemic and how they adapt to this challenging situation. Attention will be paid to how governments can be better equipped for policy learning, a crucial ingredient for adaptive policy work during crises and for effective policy-making more generally. Policy learning can be defined as a process where policy actors accumulate data and evidence, develop and draw on expertise, and adjust policy beliefs in order to deal with collective problems like a pandemic. It is expected that demands for policy learning increase when governments face catastrophic events or massive emergencies like the COVID-19 pandemic. The objective of our research is to identify and understand conditions and processes associated with policy learning among governments in Canada during and in the aftermath of the COVID-19 pandemic. More specifically, our research focuses on 1) the identification of government needs for policy learning associated with the COVID-19 pandemic, 2) on the challenges faced by governments in policy learning during and after the pandemic, 3) on understanding policy work performed by policy-makers within governments and policy leaders outside governments 4) on the identification of innovations put in place by governments to increase learning and improve policy outcomes. This research will provide key information on strategies that governments can mobilize to increase their ability to learn and deal more effectively with major policy problems in time of crisis as well as in less disruptive times.",2022,2023,Centre hospitalier de l'Université de Montréal (CHUM),108580.01,Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2022 +C19850,202109EG5,The role of anti-retroviral therapy in the increased rate of COVID-19 mortality of people living with HIV,"Recent large cohort studies have identified HIV infection as strong risk factor for severe COVID- 19. Importantly, even PLWH with low or undetectable HIV load and reconstituted CD4+ T-cell immunity still display a two-fold increased COVID-19 associated mortality over the HIV-free population. As in COVID-19, HIV infection is a strong risk factor for tuberculosis disease and mortality. Previous or current tuberculosis increased mortality of COVID-19 patients two-fold in South Africa suggesting an overlap in host vulnerability between tuberculosis and COVID-19. Recent data suggest that the cross talk of alveolar macrophages with T cells, mediated through secretion of chemokines by alveolar macrophages, is a key event in the prevention of death in COVID-19. We have shown that alveolar macrophage from PLWH mount a significantly weaker transcriptional response to infection with Mycobacterium tuberculosis leading to a significantly lower chemokine and cytokine secretion by alveolar macrophages. Unexpectedly, we showed that this reduced host responsiveness of pulmonary macrophages was primarily linked to ART and not HIV. Here we propose to test if HIV and/or ART result in reduced host responses of alveolar macrophages against SARS-CoV-2 which would likely result in increased risk of mortality. If our working hypothesis is correct, this would identify both PLWH and PrEP persons as high risk groups for adverse outcomes from COVID-19. Inclusion in the high risk COVID-19 category for PrEP users would be an important step of social justice for this historically disenfranchised population. A substantial proportion of PLWH and PrEP persons belong to groups with low socioeconomic status that are often under-represented and under-studied in advanced biomedical research, which is a shortcoming that is addressed by our experiments",2021,2022,Research Institute of the McGill University Health Centre,395000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +C19851,202005VR3,The role of interleukin-10 responsiveness in lung inflammation in SARS CoV2 infection,"A subset of patients infected by SARS CoV2 respond with overproduction of inflammatory cytokines which contribute to their acute respiratory distress and morbidity. This ""cytokine storm"" results from the imbalance between inflammatory and anti-inflammatory mechanisms. One of these mechanisms involve inflammatory macrophages which produce cytokines such as interleukin-6 and interleukin-1, and anti-inflammatory, regulatory macrophages which predominantly produce the anti-inflammatory cytokine interleukin-10 (IL10). IL10 acts on the inflammatory macrophages to temper their response. We propose to examine whether the regulatory, IL10-producing macrophages in the lung are producing appropriate levels of IL10, or whether the inflammatory macrophages are impaired in their ability to respond to IL10. We will also assess whether a small molecule SHIP1 agonist which activates the intracellular protein SHIP1 like IL10 does, can mimic the action of IL10 and reduce inflammation in SARS CoV2 infection.",2020,2021,University of British Columbia,112554,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2020 +C19852,202203MM1,The sexual and mental health of GBT2SQ men: An investigation into the health outcomes of sexualized drug use and sexualized violence among GBT2SQ men who use online technologies during the Covid-19 pandemic,"Sexualized drug use (SDU) is common among gay, bi, trans, Two-Spirit, and queer (GBT2SQ) men, and our recent CIHR study found that many GBT2SQ men have experienced sexualized violence (SV) when they engage in SDU. About 1 in 10 GBT2SQ men has experienced SV in person and about 1 in 3 GBT2SQ men has experienced SV online. Despite the high rates of SDU and SV among GBT2SQ men, both of which are reported to have increased during the Covid-19 pandemic, few studies have investigated how SDU and SV impact the sexual and mental health of GBT2SQ men. With the pandemic, GBT2SQ men are also relying on online technologies to connect now more than ever. However, the strategies that GBT2SQ men who use online technologies employ to promote their health remain under-researched. More work is needed to understand how GBT2SQ men communicate their socio-sexual interests, negotiate safety and consent, and promote their sexual and mental health with other GBT2SQ men, especially when drugs are involved. The purpose of this project is to examine the sexual and mental health outcomes of GBT2SQ men's experiences with SDU and SV relative to online technologies and the Covid-19 pandemic. This three-year qualitative research project will develop new and established community partnerships and will investigate the experiences and needs of local GBT2SQ communities through interviews with 90 GBT2SQ men (30 in Halifax, 30 in Ottawa, 30 in Montreal) and focus groups with approx. 60 service providers who work with GBT2SQ men. Project findings will offer a nuanced understanding of GBT2SQ men's experiences with SDU and SV and the sexual and mental health outcomes of those experiences, particularly in the contexts of online technologies and the pandemic. Community groups will be involved in all stages of the project, notably, to co-develop evidence-based, community-informed strategies that support and promote the sexual and mental health of local GBT2SQ men who engage in SDU and/or have experienced SV.",2022,2024,Dalhousie University,212058,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Social impacts | Community engagement,2022 +C19853,202107UIP,The South Asian Birth Cohort during the COVID-19 pandemic: understanding the impact on children and families,"The COVID-19 pandemic has led to negative health consequences for children and families including poor mental health and negative impacts to health behaviours. Given emerging evidence that racialized groups such as South Asians experienced greater COVID-19 burdens in other areas (e.g., infection rates, loss of income, mortality), it is important to examine the differences in impacts of the pandemic on racialized families. This project represents a unique opportunity to gather essential information about the health of South Asian families and children living in one of Canada's COVID-19 hotspots. We will do this by contacting families from the South Asian Birth cohort (START) study. This is a study of South Asian children and families living in Ontario, Canada. The study collects information at regularly spaced intervals over many years to help understand how diseases such as diabetes and heart disease begin. The information collected for this project will help us answer three important questions related to the impact of the COVID-19 pandemic on South Asian children and families: 1) What is the impact on the mental health of South Asian children and parents as measured with, and compared to, the Ontario Parent Survey? 2) What are changes in health-related behaviours (e.g., diet, physical activity, screen time and sleep) compared to the previous measures of these behaviours in the START cohort? 3) How are the experiences, facilitators, and barriers to health and wellbeing through the COVID-19 pandemic and recovery efforts encountered by South Asian families? All of this information will enable us to understand the range of mental health and health behaviour changes among South Asian children in Canada and the contributing factors essential to support equitable and community-led strategies which will be key to recovery.",2021,2022,McMaster University,118497.63,Human Populations,Asian,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19854,202109EG7,The Surgical EQUITY initiative: Establishing equitable access to surgery following the pandemic,"COVID-19 has disproportionately impacted marginalized populations. Not only were these patients at higher risk of becoming infected, but hospitals that cared for these patients prior to the pandemic were also disproportionately affected. Existing gradients in access to care were likely worsened. The dearth of research examining inequities in access to surgical care in Canada may stem from a belief that our universal healthcare system generally succeeds at its mission of ensuring all services are triaged according to need rather than socioeconomic status. Yet, there exists Canadian data that suggest the existence of gradients in access to other areas of care across many measures of marginalization. At the patient level, we will measure gradients in access to surgery across measures of marginalization prior to and during the pandemic. At the hospital level, we will examine whether hospitals with more COVID-19 admissions had larger surgical backlogs and how this impacted marginalized groups. At a system level, we will use mathematical modeling to examine provincial funding strategies proposed to clear the surgical backlog and assess how different strategies affect access and equity for the most marginalized populations. This will be the largest study to date to evaluate whether COVID-19 worsened access to surgical conditions across gradients of marginalization in Canada. This work will set the stage for further research directed at elucidating the consequences of socioeconomic position on patient-centered surgical outcomes, as well as specific mechanisms by which marginalization impacts surgical care. Moreover, this research is expected to have an impact beyond clinical care and research by contributing to ongoing, high-profile policy debates about the causes, consequences, and solutions to socioeconomic inequality in Canada. By framing inequality as a health issue, the proposed study has the potential to motivate public engagement on the issue.",2021,2022,Unity Health Toronto,174270.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19855,202111WI1,The Tsunami after the Earthquake: COVID-19 Impact on Cancer Care and Outcomes,"The COVID-19 pandemic has transformed Canada's cancer system. Beyond short-term disruptions on care delivery, wider and long-term impacts, arising from cancer screening delays, prolonged wait times for treatment, and undermanaged mental illnesses, have not been thoroughly examined. These disruptions will lead to future economic and societal costs, thereby extending the adverse effects of COVID-19 for many years to come. Whether the associated impacts are accentuated in marginalized populations (immigrants, ethnic minorities, lower socioeconomic status regions) are also unknown. To design an effective and equitable cancer system recovery plan, it is imperative to consider these wider, and potentially population-specific, consequences of COVID-19. This proposal addresses this urgent need. This study brings together healthcare leaders, physicians and other stakeholders to assess COVID-19's wider impacts on cancer care delivery and patient outcomes in Ontario. Pre-pandemic and pandemic comparisons will be made related to three specific aims: 1) quantify changes in screening uptake (for cervical, breast and colorectal cancers); 2) measure shifts in cancer staging and managing newly diagnosed cancer patients, including initial treatment modality (surgery, radiation therapy, or chemotherapy) and wait times; and 3) examine patient-reported depression/anxiety symptoms during cancer treatment and subsequent receipt of therapy. Additional analyses will assess if the trends of 1)-3) point to exacerbated disparities in marginalized populations (immigrants, rural residents, individuals experiencing material deprivation, and Indigenous populations). Lastly, through engagement of national/provincial policy leaders and clinical leads, recommendations on how to minimize the impact of the pandemic on cancer care and improve preparedness for future health emergencies will be provided.",2021,2023,"Sunnybrook Research Institute (Toronto, Ontario)",267828.17,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19856,202111WI1,"The Wider Impact of the COVID-19 Pandemic on Gestational Diabetes Screening, Diagnosis, and Outcomes","Gestational diabetes is one of the most common medical problems in pregnancy. It occurs when there are high blood sugar levels late in pregnancy. Gestational diabetes requires treatment during pregnancy to decrease the risk of complications for both mother and baby. The Diabetes Canada guidelines recommend that all pregnant individuals be screened for gestational diabetes between 24 and 28 weeks of pregnancy. This screening test involves going to a lab, having a sugary drink, waiting an hour in the lab, and having a blood test drawn after the hour. With the COVID-19 pandemic, huge changes were made to healthcare delivery. Diabetes care changed from being delivered in person to mostly being done virtually. Specialized staff such as diabetes nurses were redeployed to COVID-19 supportive roles. Also, pregnant patients and obstetric care providers voiced concerns about the risk of getting COVID-19 while doing the gestational diabetes screening blood tests. To address this, our team developed a COVID-19 screening strategy for centres that were severely affected by the pandemic. We do not know what impact the pandemic or the new screening criteria had on pregnant individuals and their babies. Research objective: We will examine if the COVID-19 pandemic led to unintended harm in the pregnant population regarding gestational diabetes screening, pregnancy outcomes and missed diagnoses. Methods: We will perform a population-based study of pregnant individuals in Alberta, Ontario and Manitoba. This study will use established databases in the three provinces to determine the extent of the impact of the COVID-19 pandemic on the health of mothers and their babies. Impact of research: It is essential that we identify the impact COVID-19 has had on this high-risk pregnant population. The results of this study will inform best practices regarding the screening for and treatment of gestational diabetes in future health emergencies and pandemics.",2021,2023,University of Manitoba,283452,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19857,202002OV3,Therapeutic approaches to SARS-CoV-2 and other pathogenic coronaviruses,"Coronaviruses can cause serious diseases in humans and animals. Over that last two decades, we have seen the emergence of three deadly coronaviruses, the most recent of which SARS-CoV-2 is still spreading rapidly. Antivirals developed for other viruses are presently being tested in clinical trials in China, but there is no indication that these drugs will work against SARS-CoV-2. Currently, public health measures and quarantine are the only means to limit spread of SARS-CoV-2. As such, antiviral therapeutics and vaccines are both desperately needed to mitigate the effects of SARS-CoV-2 and future coronavirus outbreaks. Here, we present a strategy for testing novel antiviral drug candidates and vaccines as well as molecular tools to understand SARS-CoV-2 biology. By focusing initially on drugs already approved for use in humans for other indications, our goal is to identify compounds with activity against SARS-CoV-2 that can be rapidly approved for use in the clinic. In addition, our expertise in immunology and vaccinology against coronaviruses positions us very well for developing novel vaccine candidates. Finally, we will create molecular tools including modified SARS-CoV-2 viruses. Some of these tools which will not require high level containment, will be made available to a wide group of researchers so that they can also screen for antiviral compounds and study virus biology without the need for specialized containment facilities.",2020,2022,University of Alberta,748725,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2020 +C19858,202107UI1,To assess the impact of COVID-19 on prenatal education and pregnancy outcomes in mothers and children in remote First Nations communities in Manitoba,"COVID-19 pandemic seriously affected the prenatal education for pregnant women and potentially has long lasting adverse effects on the pregnancy outcome and health of mothers and their children. First Nations (FN) pregnant women and children particularly those living in remote communities, may be more severely affected. We propose to determine the impact of COVID-19 on the interruption of prenatal education and resultant consequences including GDM, cesarean section, infant growth and breastfeeding initiation in FN women and their offspring in Manitoba via a database study, and on prenatal education, food intake, physical activities, spousal support, breastfeeding initiation and duration to pregnant FN women in remote Island Lake communities compared to those in rural FN communities in Manitoba, and FN and non-FN pregnant women and children living in Winnipeg via online or hardcopy survey with the support from regional health authority, communities, health workers and community Elders. The results of the proposed study will demonstrate the negative consequences of COVID-19 on prenatal education, lifestyle, family support, child growth and pregnancy outcomes in FN and non-FN mothers and their children in urban, rural and remote communities. The findings from the project may help to understand and mitigate the impact of COVID-19 on the health of FN pregnant women and their children to identify the areas in pregnancy and postpartum programs, which are required to be improved in remote and rural FN communities and to protect the health and wellness of Indigenous women, children and their families.",2021,2022,University of Manitoba,118500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19859,202005VR1,Towards a comprehensive understanding of adaptive immunity to SARS-CoV-2,"The vast majority of people who get COVID19 fully recover from infection. This means that their immune system has successfully eliminated the virus. After we recover from a virus infection, the immune system leaves behind white blood cells, called memory cells, that can remember the previous infection and prevent that infection from recurring upon re-exposure. This is the basis of how vaccines work. After we recover from infection, two kinds of white blood cells persist, T cells and B cells. T cells and B cells have molecules on their surface that allow them to recognize the specific virus they were first exposed to. B cells give rise to antibody producing cells, while T cells can eliminate infected cells. Some antibodies can bind the virus in such a way that they fully block the virus from entering the cell. These are called neutralizing antibodies and these are ideal to fully protect us from being infected again. However, in some infections, weak antibodies, instead of neutralizing the virus, can actually make things worse by promoting uptake of the virus into cells or by overstimulating certain cells of the immune system. Therefore, there is a pressing need to understand the details of the immune response in COVID19 patients. We need to understand what parts of the virus are recognized when we have an immune response associated with a good outcome and what if any aspects of T and B cell responses are associated with a bad outcome. By studying the immune response in asymptomatic, mild and severe cases in depth, we hope to determine the correlates of a good immune response and use this information to design vaccines and to monitor people for the correct immune responses. For some infections T cell and B cell responses last a lifetime, whereas for other infections they do not last as long. Our study will develop the tools we need to follow how long the immune response to COVID19 infection lasts and to help with evaluating the level of protection in the population.",2020,2021,University of Toronto,802297.5,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Immunity | Pathogen morphology, shedding & natural history",2020 +C19860,202002OV3,Towards anti-COVID-19 therapeutic development by targeting the viral papain-like proteinase,"When positive-stranded RNA viruses such as the causative agent for the 2019-2020 novel coronavirus (SARS-CoV-2) outbreak enter an infectious cycle in the cell, their RNA genomes hijack the host cell's protein production machinery to mass produce large continuous viral polyproteins in a process called translation. In order to make progeny viruses, these viral polypeptides need to be processed into smaller, individually functional protein programmed to perform specific tasks, e.g., replicating the RNA genome, assembling the protein coat for progeny viruses, packing the newly synthesized RNA genome into the assembled viral capsid, and subverting or disabling the host cell's antiviral defense mechanisms. Two virally encoded proteinases, the papain-like (PL) and the 3C-like (3CL) proteinases, carry out the job of ""clipping"" the viral polypeptides into individual viral proteins. The PL is translated before the 3CL hence it likely takes precedence in performing ""cuts"" in the polyprotein, releasing an initial batch of viral proteins to mount the first wave of suppressive attack on antiviral host defense. In addition, coronavirus PL directly participates in preventing type I interferon activation, an important step leading to antiviral defense. Last but not the least, PL1 is part of non-structural protein 3 (NSP3), which is an indispensable component of the membranous complex where viral RNA genome is replicated. Taken together, PL of the novel coronavirus makes a good antiviral target for the development of therapeutics. Inhibiting PL would not only halt viral protein and RNA production at an early stage but would also help restore host antiviral defense. In this proposal, we seek to solve the 3-dimensional structure of SARS-CoV-2 PL and then use the structural knowledge to aid our search of small molecules that can inhibit the functions of PL. We will work with our collaborators to optimize the top inhibitors and test these inhibitors in cell and animal infection models.",2020,2022,University of Alberta,186600,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C19861,202002OV8,Towards Better Governance of Zoonotic Disease Risk: One Health Principles in the Coronavirus (COVID-19) Response,"The unfolding 2019-nCov outbreak presents an opportunity to establish a real-time monitoring infrastructure to study how One Heath principles are implemented in the global governance of infectious diseases (IDs). Through employing rapid environmental scan methodology and building on already existing research collaborations, we will be able to produce immediate results focused on the global coordination and response system that can feed into better global governance of 2019n-Cov, improving evidence-based decision-making and enhancing international collaborative efforts to mitigate the spread of 2019-nCov.",2020,2022,University of Ottawa,374478,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Animal and environmental research and research on diseases vectors,,2020 +C19862,202107UIP,Towards Recovery from the COVID-19 Pandemic - the TARGet Kids! Study of Children and Families,"The COVID-19 pandemic is having an unprecedented negative impact on the health and well-being of Canadian children and families. As Canada enters the recovery stage, research is needed to understand and monitor the ongoing impact of the COVID-19 pandemic on multiple domains of children's health and well-being. We propose to use the TARGetKids! longitudinal cohort study of Children and Families, with data already collected pre-pandemic and since April 2020 to understand the impact of the COVID-19 public health policies (lockdowns and school closures by dates, and adherence to six public health measures) on the health behaviours (physical activity, screen time, outdoor time, sleep, and eating behaviours), growth (body mass index), school outcomes (academic performance and school readiness), and mental health over time in young children aged 0-12 years in the Greater Toronto Area. We also plan to understand the roles parental stress and socio-demographic factors play in these relationships. With repeated data collected before the pandemic and during the first 1.5 years of the pandemic and detailed socio-demographic data collected from a diverse population, we plan to continue to collect repeated data on multiple domains of child health over the next year from children and parents to evaluate the long-term effects of the COVID-19 pandemic on Canadian children and their families. Real-time data from a diverse children population are crucial to guide the planning and delivery of mitigation strategies to support the recovery from the COVID-19 pandemic.",2021,2022,Hospital for Sick Children (Toronto),118341.21,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +C19863,202107UIP,Transition to Adulthood during COVID-19: Lessons Learned from Canadian Youth with Special Healthcare Needs and their Families to Foster Effective Transitional Care Interventions.,"Over the past 18 months, COVID-19 has impacted nearly every aspect of our usual ways of living. For Youth with Special Healthcare Needs (YSHCN), COVID-19 created even more disruption such as the fear of COVID-19 worsening fragile health, disruption of usual daily routines, especially school, lack of usual health and social supports and services, and social isolation. While we know from the YSHCN and their parents in our practices that the pandemic has had a serious negative impact on their mental health, some positive outcomes have been reported. For example, healthcare providers, YSHCN, and parents have discovered that online options for visiting health care providers, accessing supports and transition offer more flexibility and ease of attending appointments, and in the timing of transfer to adult services. This study will explore the impact of the COVID-19 pandemic on the health of YSHCN during their transition to adult services (between 16-24 years of age). We will examine experiences in both healthcare transitions as well as co-occurring life transitions for this population. Through collection of data through interviews and surveys, we will get a better understanding of the negative outcomes of COVID-19 for the youth and their families, as well as opportunities the pandemic has created for this population. We will also gather data around solutions that are working, those which should be started and ideas for the future.",2021,2022,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",118470.77,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19864,202111WI3,"Tushirikiane-4-Uthabiti (Supporting Each Other For Resilience): A mixed-methods mobile health study to understand and address the social and health impacts of COVID-19 among urban refugee youth in Kampala, Uganda","THE ISSUE: The COVID-19 pandemic has exacerbated refugee health disparities. Our team documented high food insecurity, depression, alcohol use, and unmet HIV prevention needs with urban refugee youth in Kampala, Uganda, a low-income country and the largest refugee host in Sub-Saharan Africa with 1.5 million refugees. There is an urgent need to understand, and identify effective interventions to address, the indirect and wider health consequences of COVID-19 among youth in low-income humanitarian contexts. We focus on urban refugee youth in Kampala, Uganda, where there are 93,000 refugees largely living in slums. OUR IDEA: We will develop and evaluate the effectiveness of an mHealth (WhatsApp, SMS) intervention in reducing economic insecurity (food insecurity, poverty), increasing HIV prevention (HIV testing uptake, condom use, PrEP uptake), and improving mental health (reducing depression and problematic substance use) outcomes among an existing cohort of urban refugee youth aged 16-24 in Kampala. Our project involves: 1) qualitative phone interviews with refugee youth and key informants to understand refugee youth priorities and aspirations for reducing COVID-19 impacts; 2) tailoring evidence-based interventions for livelihood strengthening, reducing psychological distress, and HIV prevention (HIV self-testing, PrEP linkages) for refugee youth in a 16-week mHealth (SMS, WhatsApp) intervention; 3) conducting a single arm, pre-test/post-test trial to test the intervention effectiveness in reducing poverty, improving mental health, and increasing HIV prevention cascade engagement; 4) knowledge mobilization, including a toolkit, comic book manual and radio drama, as well as policy analysis and refugee youth working paper. Findings will advance new knowledge of indirect and wider health impacts of COVID-19 among refugee youth, and provide effectiveness data for mHealth strategies to address the syndemic of poverty, HIV and poor mental health with urban refugee youth.",2021,2023,University of Toronto,381412,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa,Digital Health,,,Canada,Uganda,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C19865,202005VR5,Uncovering longitudinal patterns of resilience and vulnerability in a pandemic: The All Our Families COVID-19 Impact Study,"The psychological and social effects of the COVID19 pandemic are pervasive and are impacting current mental health and relationships, with potential long-term effects, notably in youth. Youth is a developmental period of significant social, emotional, biological, and contextual change, simultaneously associated with a surge in mental health difficulties. Preliminary evidence at the national level is indicating reduced mental health during the pandemic, particularly among youth. High-quality, contemporary data on coping and recovery for families and youth during and after an unprecedented pandemic is crucial to inform further action and resource allocation in any future periods of lockdown, increased or re-infection, and future pandemics. Further, the acute and sustainable costs and benefits of aggressive public health measures such as physical distancing on the well-being of families and communities are unknown. The All Our Families (AOF) study, an ongoing prospective pregnancy cohort in Calgary, will survey families at three times points over one year to capture the discrete and longitudinal patterns of direct and indirect impacts of the pandemic on mental health, social connections, school achievement, sleep, and screen-time. AOF is uniquely positioned to disentangle emerging and sustained vulnerabilities from pre-existing vulnerabilities to development using longitudinal data that reflect the individual, family, and community determinants of health. Longitudinal data analysis will uncover patterns of resilience and vulnerability immediately, and over time for mothers and youth. Identification the factors that influence family and youth health and well-being during a pandemic is critical to the development of public health communications and strategies to improve outcomes.",2020,2021,University of Calgary,197561.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C19866,202111WI1,Uncovering the Wider Impact of COVID-19 Measures on the Lives of Children with Complex Care Needs and their Families,"Background. Children with complex care needs are a vulnerable population served by our pediatric health and social care systems. Prior to the COVID-19 pandemic, caregivers of children with complex care needs reported numerous gaps in programs and services including a lack of care coordination and communication between service providers. COVID-19 public health measures resulted in rapid changes to many health and social supports across the Maritime provinces that these families rely on to maintain and optimize health and well-being. It is unclear how these changes impacted children with complex care needs and their families. Objectives. This research aims to understand how policy and services changes implemented in the Maritime during the COVID-19 pandemic impacted the health and well-being of children with complex care needs and their families. This will be achieved by: 1) Mapping COVID-19 public health restrictions and service changes impacting this population; and 2) Exploring with families living with complex care needs how they experienced these changes. Methods. We will work with our research partners to understand the experiences of families living with complex care needs in the Maritimes. We will conduct an environmental scan of publicly available documents to identify policy and service changes during the pandemic relevant to this population. We will also conduct interviews with policy makers to further understand the development and implementation of policy and service changes. Finally, we will interview children and caregivers from the Maritimes to explore their experiences with these changes. Impact. Children and families with complex needs experience many service and support gaps in the Maritimes. Our approach will allow us to identify key components for building a responsive COVID-19 inter and intra provincial policy and service strategy to meet the needs of this vulnerable population.",2021,2023,IWK Health Centre (Halifax),325431.02,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other | Unspecified,Caregivers | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Other secondary impacts,2021 +C19867,202108VCF,Understanding and evaluating the role of partnerships with Canadian minority faith-based communities in improving vaccine confidence in communities and vaccination program implementers,"COVID-19 is part of a pattern of increasingly frequent epidemics that have coincided with several pre-existing crises, including rising racial, social and health inequities. The focus on the development and deployment of COVID-19 vaccines has drawn attention away from the extent to which the lack of confidence in vaccines remains a persistent challenge, particularly among Indigenous, Black and other racialized groups in Canada and in other countries. The introduction of new vaccines is not necessarily followed by trust in (i) the effectiveness and safety of vaccines; (ii) the system that delivers them, including the reliability and competence of the health services and health professionals and (iii) the motivations of policy-makers who decide on the needed vaccines. Several historical and contemporary dimensions interplay to influence vaccine hesitancy. In this project, we seek to understand the role religion and collaborations with faith-based organizations play in increasing vaccine uptake. Currently, public health interventions to address vaccine confidence have relied on faith-based leaders as trusted messengers or used houses of worship as vaccine clinics. We will identify and evaluate community-centered interventions that aim to improve vaccine confidence among Black, South Asian, Middle Eastern, or newcomer communities particularly in the region of Peel (Ontario). Our project will help contribute knowledge about what interventions work, for whom, under what contextual circumstances, and whether these interventions are scalable in equitable ways. We will co-implement evaluations of promising community-based interventions while applying a model to build implementation research capacity among vaccine program managers.",2021,2023,University of Toronto,157898.09,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C19868,202107UIP,"Understanding and Mitigating the Impact of the COVID-19 pandemic on Children, Youth, and Families living with an Eating Disorder: A National Implementation Study of a Virtual Parent-Led Peer Support Intervention","The COVID-19 pandemic has worsened conditions for individuals with eating disorders (EDs). In Canada, we have experienced a surge in new pediatric ED cases and hospitalizations and long treatment waitlists, with parents experiencing anxiety due to a lack of support. As it has not been rigorously studied, there is an urgent need to understand and mitigate the impact of the COVID-19 pandemic on children, youth, and families living with EDs across Canada. Our proposed research has two goals. First, we plan to understand the impact of the COVID-19 pandemic faced by this population throughout the country, as well as describe stakeholder views on virtual parent support groups. Given the increased burden faced by parents of children with EDs during the COVID-19 pandemic, our second goal is to study whether the national implementation of virtual parent support groups helps to mitigate the impact of the pandemic among affected parents. We will use qualitative semi-structured interviews, to gather an understanding of the impact of the pandemic on relevant stakeholders across the country. At the same time, we will evaluate the feasibility and acceptability of the implementation of virtual parent support groups in several regions of Canada by examining parent and provider experiences. Our team is well positioned to respond to this rapid research funding opportunity, as experts in EDs, implementation science, community-based research, and peer support are collaborating on this project. Studying the implementation and effectiveness of parent support groups is essential, particularly during the present and post-pandemic era, when vulnerable populations are in dire need of support.",2021,2022,McMaster University,118498.42,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19869,202107UIP,Understanding and responding to self-perceived stressors among parents and youth due to the COVID-19 pandemic: Informing an evidence-based public health approach,"The COVID-19 pandemic has been a stressful time for families. Necessary public health measures have been put in place to reduce the spread of infection, illness, and burden on the healthcare system. However, these restrictions may also create other problems, challenges and stressors for youth and parents. Although many important studies were conducted in the first year of the COVID-19 pandemic, more research is needed to understand stress and needs of youth and parents within the second year of the pandemic and beyond. The goals of the proposed research are to examine how pandemic-related stressors are associated with mental health, physical health, and substance use among youth and parents and to understand what youth and parents identify as needed help or support to recover from and thrive post-pandemic. This research will also investigate if outcomes are worse for those who have experienced adversity in childhood, who reported financial burden during the pandemic, and who had poor mental health before the pandemic began. A focus will also be placed on understanding differences among males and females. The proposed research will use existing data from the Well-Being and Experiences Study (The WE Study), which includes data collected pre-pandemic and during the first year of the pandemic. The proposed research will allow for additional data collection in the second year of the pandemic (2021-2022) among youth and parents. The team are experts in childhood adversity, mental health, substance use, and research methods. The current proposed research will provide essential evidence to help develop clinical and public health responses to improve health and support the recovery for youth and their parents.",2021,2022,University of Manitoba,111958.8,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Drug users | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19870,202111WI1,Understanding and Responding to the COVID-19 Pandemic Effect on the Magnitude of Alcohol-Related Liver Disease in Alberta.,"Approximately 1 in 4 Canadians is practicing high-risk alcohol drinking (more than 10 drinks a week for women and 15 drinks a week for men) based on the Canadian guidelines. There has been a striking increase of alcohol sales and consumption in relation to the pandemic. One in 3 adult people who practice high-risk alcohol consumption (also known as heavy alcohol drinking) has alcohol-related liver disease (ArLD) which accounts for nearly 50% of deaths related to end-stage liver disease. ArLD patients experience worse clinical outcomes compared to other patients with chronic liver disease. The severity of ArLD depends on alcohol consumption and stage of liver scarring, known as fibrosis. Currently, there are no clinical care pathways designed for early detection of individuals with ArLD and risk stratification before they are diagnosed with end-stage liver disease. With the recent increase in alcohol sales, hospitalizations, and mortality related to ArLD in Canada, there is an urgent need to establish a clinical care pathway to identify and risk stratify patients with ArLD. In our proposed project, we aim to evaluate the burden of ArLD in Alberta in relation to the pandemic. Our goal is to develop and evaluate the first clinical care pathway to identify and risk stratify patients with ArLD in primary care in the Calgary Health Zone using simple non-invasive serum markers. We will connect patients at risk of advanced liver scarring due to ArLD with multi-disciplinary teams to provide medical and social care. We will also evaluate the performance of our clinical pathway and compare two common modalities to risk stratify liver fibrosis among patients with ArLD (serum-based and ultrasound-based). This project is novel, timely, and essential to meet the urgent and unmet need of identifying and supporting the increasing number of ArLD patients in relation to the COVID-19 pandemic.",2021,2023,University of Calgary,334061.77,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19871,202108VCF,Understanding and strengthening vaccine confidence among temporary foreign workers in Manitoba: A community-based participatory approach,"In Manitoba, South-east Asians, Africans, South Asians, Latin Americans, Black people, Filipinos and North American Indigenous peoples shoulder the burden of COVID-19 infections compared to their White counterparts. According to the Government of Manitoba's 2021 Race, Ethnicity and Indigeneity (REI) Analysis Report Wave Three, lower income racialized people were most likely to live in overcrowded and/or inadequate housing, which is the most common acquisition setting. Such overcrowding characterizes the living arrangements of many migrant workers in Manitoba. Earlier REI data showed that BIPOC individuals, particularly migrant workers, were more likely to be employed in higher-risk occupational settings, including food processing and food services, manufacturing and transportation, homecare work and farming. Although we are beginning to better understand the vulnerability of migrant workers to COVID-19 infections in Canada, there exists a major knowledge gap around vaccine confidence in this population. For this reason, we aim to strengthen vaccine confidence among temporary foreign workers in Manitoba by examining it within the wider structural context of inequality. Drawing upon a partnership between the migrant workers' rights organization, Migrante, and the University of Manitoba Institute for Global Public Health, we will pursue two objectives. Objective 1: to generate new knowledge on ""vaccine confidence"" that sheds light on systems of inequality within the Temporary Foreign Worker Program. Objective 2: to build a community-owned database that can guide Migrante's efforts to enhance vaccine uptake among temporary foreign workers. This approach to data justice will sharpen the focus of Migrante's ongoing health advocacy work by enabling them to generate and follow key health indicators, geographic coverage targets, and COVID-19 vaccine uptake among temporary foreign workers in Manitoba.",2021,2023,University of Manitoba,157289,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19872,202109EG2,Understanding attitudes and beliefs toward the COVID-19 vaccines among youth with mental illness,"Background: People with mental illness (MI) have increased risk of contracting, and dying from, COVID-19 compared to the general population. Possible explanations include behavioural and structural factors (e.g., living in congregate settings). While COVID-19 vaccine uptake rates for people with mental illness is lacking, influenza vaccination uptake is generally lower than the general Canadian population. COVID-19 vaccines are safe and effective, yet studies show that 11% to 18% of Canadians are hesitant. Black Canadians, Indigenous peoples, newcomers, and youth tend to have higher vaccine hesitancy and are more likely to experience social and structural barriers to accessing vaccinations. Youth between the ages of 16 and 29 are particularly vaccine-hesitant, with some of the lowest vaccination rates in Canada to date. Therefore, youth with MI may require more tailored interventions to increase uptake of COVID-19 vaccines. Research Questions: 1) What are the beliefs and attitudes of youth with MI towards COVID-19 vaccines, including acceptance of vaccines? 2) What are youths' preferred method(s) of receiving and searching for information about COVID-19 vaccines? Methods: We will conduct qualitative semi-structured interviews inquiring about youths' information needs, attitudes toward COVID-19 vaccines, and trust towards the healthcare system and vaccine manufacturers. We will also explore perceived severity of having COVID-19; susceptibility to developing COVID-19; benefits of, and barriers to, the vaccine and cues to action. Transcripts will be thematically analyzed. Anticipated outcomes/impact: This co-designed project aims to promote vaccine uptake among youth with MI by 1) identifying recommendations for developing targeted, evidence-based public health campaigns, with a focus on COVID vaccines; 2) co-creating and piloting a vaccine campaign with youth with MI; and 3) develop clinical tools (e.g., clinical conversation guides) tailored for this population.",2021,2022,Centre for Addiction and Mental Health (Toronto),113308.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C19873,202111WI2,Understanding changes in acute care and mortality patterns among children and youth with medical complexity (CMC) during the COVID-19 pandemic,"Children have been less likely to have severe outcomes from COVID-19 during the pandemic. Reports suggest children have also had fewer acute illnesses requiring hospitalization, particularly those hospitalizations that are caused by communicable diseases, such as respiratory infections. Acute respiratory infections substantially impact health outcomes of children with medical complexity - defined as those children with chronic conditions that result in increased health needs, disabilities, and high healthcare use. While the full scope of restrictions that existed in the worst phases of the pandemic--such as school closures--have caused harms to children with medical complexity, there may be value in continued use of some less restrictive public health measures, such as masking, handwashing, social distancing, and vaccination, to protect children with medical complexity, particularly during periods with high rates of community transmission of viral respiratory infections. We propose to begin to understand this phenomenon by analyzing data from across Canada (except Quebec) to compare rates of hospitalization, ICU admissions and death within hospitals during the pandemic compared to previous non-pandemic years. We will look specifically at changes in hospital admissions that include severe respiratory illnesses. We will evaluate rates for children with specific types of medical complexity that are at particular risk of severe respiratory illness, such as children with brain-based disabilities. Our strong partnership with knowledge users with input from youth and families will ensure that study findings inform preparedness for future health emergencies that threaten the health outcomes of children with medical complexity.",2021,2023,Hospital for Sick Children (Toronto),204207.89,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons | Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2021 +C19874,202107UIP,Understanding Dynamics of Risk and Protective Factors and Children's Mental Health During the COVID-19 Pandemic,"Canadian children have experienced deteriorations in their mental health during the COVID-19 pandemic. Recent studies have shown that many factors are contributing to worsening mental health in children, including increases in parent stress and harsh parenting, more screen time, and less social contact. On the other hand, several important protective factors have been identified that are supporting children's coping, such as physical activity, healthy sleep routines, and positive parenting. At present, we know little about how these risk and protective factors work together to predict children's mental health, information that is needed to guide recovery efforts. We will recruit 500 parents and children age 9-12 years from the CHILD Cohort Study to participate. The CHILD study has followed over 3400 children from birth to present in four sites across Canada (Vancouver, Edmonton, Manitoba, and Toronto). We will ask parents and children to answer questions twice daily for 2 weeks about parenting, parent stress, social contact, physical activity, sleep, screen time, and children's mental health. We will analyze the data using a new method called dynamic network analysis, which can identify chains of association between items we are measuring. For example, we may learn that reducing parent stress leads to more consistent parenting, which is in turn associated with less screen time and fewer child behaviour problems; or, that more anxious feelings lead to children seeing friends less, creating a cycle of sadness and less social contact. We will also test whether risk and protective factors operate differently depending on child age, parent or child gender, and geographic region. By identifying chains of association and feedback loops between risk and protective factors and mental health, we will provide new information about the most important factors to target in efforts to support children's mental health during the pandemic.",2021,2022,Centre for Addiction and Mental Health (Toronto),111874.27,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19875,202111WI3,Understanding How COVID-19 has Affected Hospital Performance,"IMPORTANCE: The novel coronavirus disease (COVID-19) has caused significant challenges for health systems worldwide and has especially challenged the efficiency and effectiveness of many healthcare institutions. Our proposed research will focus on analyzing the impact of COVID-19 on the performance of hospitals across Ontario and generating insights into whether, and to what extent, hospital performance has changed due to COVID-19. METHODS: We will employ descriptive statistics, regression techniques, causal methods, and data envelopment analysis (DEA) to evaluate the relative clinical capabilities of hospitals across Ontario before and after COVID-19. We will use data from the General Medicine Inpatient Initiative (GEMINI) data repository collected from 33 large hospitals across Ontario (covering ~60% of all of Ontario's medical hospital beds). Our proposed research will aim at creating an efficiency classification that identifies high-performing hospitals and determines how each hospital's relative performance ranking has changed due to COVID-19. Subsequent quantitative and qualitative analyses will then identify factors that influence a hospital's performance in combating COVID-19, allowing for interventions to improve preparedness for future health emergencies and pandemics. IMPACT: Our proposed research will advance our understanding of the impact of COVID-19 on hospital performance and allow healthcare institutions to learn from efficient hospitals which have realized relative success in combating COVID-19. Further, this research will generate evidence about all adult medical and intensive care hospitalizations during the pandemic, and thus is directly relevant to numerous marginalized, high risk, and underrepresented populations.",2021,2023,York University,395000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19876,202002OV8,Understanding non-compliance with the International Health Regulations (2005): Recommended strategies to inform and strengthen global coordination of the COVID-19 outbreak response,"Outbreaks such as the novel coronavirus (COVID-19) can result in inappropriate, excessive and counterproductive measures that hinder global coordination of outbreak response. Moreover, they compound loss of life and illness by contributing to unnecessary social and economic disruption, and can discourage countries from open reporting for fear of retaliation. For these reasons, the World Health Organization (WHO) declaration of the COVID-19 outbreak as a public health emergency of international concern (PHEIC) included recommended, evidence-based measures for detection, containment and control based on available data. These measures adhere to International Health Regulations (IHR) principles concerning human rights, proportionality, and unnecessary interference with trade and travel. Yet preliminary analysis suggests a higher number and range of non-compliant measures are being adopted than previous PHEICs. The goal of this project is to strengthen global coordination of the COVID-19 outbreak response through a fuller understanding of crossborder measures adopted, their likely positive/negative impacts, reason(s) for adoption, and strategies to increase compliance. This project applies a mixed-methods approach to achieve 4 objectives: a) define, categorize and track crossborder measures adopted during the COVID-19 and previous outbreaks; b) systematically review existing evidence of their public health and wider impacts; c) understand decisions to adopt compliant or non-compliant measures in 4 case study settings (Australia, Canada, Hong Kong and US); and d) identify strategies to encourage increased compliance. Working closely with key knowledge users, including WHO, we will collect and analyze new data, and combine it with our existing datasets to conduct real time quantitative cross-outbreak analysis. The key outcome of this project is to mitigate the rapid spread of COVID-19 through practical, evidence-informed strategies that strengthen global coordination.",2020,2022,Simon Fraser University,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | Western Pacific,,,,Canada,Australia | Canada | Hong Kong | United States of America,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C19877,202109EG7,Understanding preferences for substance use health services for problematic alcohol use during the COVID-19 pandemic,"The COVID-19 pandemic has brought about numerous negative mental health effects and created many new barriers for accessing substance use health services. Various public health guidelines, such as physical distancing and mobility restrictions (lockdowns and stay-at-home orders), have contributed to reducing critical harm reduction services, counselling, and psychotherapy. This alludes to the study's goal to understand how substance use health services for problematic alcohol use (PAU) should be designed during the COVID-19 or future pandemics. Considering the above, those with lived experiences must be involved in the design of mental health and addiction services to ensure that such services are relevant and responsive to the needs of populations. Therefore, this study will describe individuals' preferred characteristics of substance use health services for PAU, assess how the pandemic may affect their preferences, and evaluate the relative importance of the preferred characteristics. This study will use qualitative and quantitative research methods, such as literature review, interviews, and a national online survey. The study will account for participants' socio-demographic information, including but not limited to sex, gender, in the design, analysis and knowledge translation steps. Understanding preferences could help policymakers and service providers redesign substance use health services to meet the needs and improve the health outcomes of individuals with PAU, ultimately improving their quality of life.",2021,2022,Ottawa Hospital Research Institute,207165.65,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19878,202002OV7,"Understanding Social Perceptions of Risk, Information Sources, Trust, and Public Engagement Related to the COVID-19 Outbreak","The aim of this project is to conduct rigorous research that (a) documents, preserves, and shares perishable data about the social dimensions of an emergent outbreak, and (b) that translates and mobilizes this knowledge into tangible countermeasures that can aid in minimizing the negative impacts of the disease on individuals and communities. With the emergence of a new disease like COVID-19, there is the potential for significant fear, stigmatization, and misinformation. It is essential to understand how these phenomenon operate; to trace how they affect public attitudes, fears, and beliefs; and to support evidence-based communication by government and expert public health sources that can help to minimize panic or stigmatization, support the adoption of appropriate precautions, and promote effective and pro-social responses. We combine four data sources (a nationally-representative survey sampling 300,000 Canadian households three times over the next two years; follow-up interviews with 135-165 participants; social media data; and mainstream media discourse analyses) to investigate a series of research questions surrounding public perceptions, fears, and reactions. The survey and interviews will provide core data on public perceptions of the risk of COVID-19, who Canadians are turning to as experts on the topic, and what information they are seeking. We correlate this data with analyses of the content being shared through social and traditional media platforms. This project supports the response to COVID-19. By better understanding Canadian risk perceptions, fears, and information sources, we can support the development and testing of more effective strategies for sharing reliable information and garnering trust. Longitudinal, cross-Canada surveying allows for regional analysis of interventions, rapid identification of what information Canadians are seeking, and the creation of pathways for sharing public knowledge and opportunities for engagement.",2020,2022,York University,0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication,2020 +C19879,202109EG3,Understanding the COVID-19 Journeys and Vaccine Experiences of Racialized and Immigrant Communities in the Greater Toronto Area,"This research explores the ""COVID-19 journeys"" of racialized and immigrant communities within Peel Region to increase the cultural awareness, safety, and efficacy of health messaging and care for racialized urban communities within Canada. Our novel approach combines spatial modelling of COVID-19 case rates and vaccine coverage with a qualitative investigation into the pandemic experiences of people living in Peel Region communities. Particular focus will be placed on areas with unique combinations of case exposure and vaccine coverage to reveal what life has been like for people living on the 'front lines' of the COVID-19 pandemic. We are particularly interested in what combinations of factors led to high exposures and how families and communities worked together to support each other during the crisis. We are also interested in the roles played by young adults in immigrant families as interpreters of health information. Furthermore, we are interested in what sources of information people use to determine what behaviours are risky or safe concerning COVID-19, particularly around vaccines. Our overall goal is to contextualize the pandemic experiences of racialized individuals, families, and communities in ways that offer new insight into the factors that shaped the disproportionately high burden of COVID-19 morbidity and mortality borne by these communities. Our team's strong links with regional and provincial public and primary health service providers, and our strong track record of community-engaged scholarship within the Greater Toronto Area, will ensure knowledge is shared and mobilized to support action that ultimately leads to improvements in health services for racialized and immigrant Canadians.",2021,2022,University of Toronto,157210,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Internally Displaced and Migrants | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Community engagement | Communication,2021 +C19880,202111WI1,Understanding the effects of hospital capacity strain on quality of hospital care for patients admitted to medical and ICU wards during the pandemic and evaluating interventions to mitigate hospital capacity strain,"COVID-19 placed significant strain on hospital capacity in Canada. We will study the effect of this strain on the quality of acute care for adult medical and intensive care unit (ICU) admissions, the two main locations of COVID-19 care and subsequent hospital strain. To mitigate capacity strain, Ontario hospitals engaged in inter-facility transfers of >3000 patients and extended ICU care onto medical wards. There is limited evidence about if these interventions were safe or effective for transferred patients or for critically ill patients cared for in a non-ICU setting. Little is known about how hospital strain, or the above interventions, impacted marginalized populations. Our research aims to investigate how hospital strain, and the two major capacity-mitigating interventions, affected quality of acute care for hospitalized medical and ICU patients. We will use data from GEMINI, a clinical and administrative data repository with data from 33 large hospitals across Ontario (~60% of Ontario's adult medical hospital beds), linked to population data at ICES. GEMINI is the largest clinical research dataset on hospitalized patients in Canada. First, we aim to characterize the effect of hospital strain on quality of care for medical and ICU patients. Then, we aim to investigate how large-scale inter-facility transfers and extension of ICU onto the ward affected clinical care. We will study prevalence and severity of both COVID-19 and non-COVID-19 hospitalizations, the impact on care for patients with chronic conditions, and the impact on marginalized groups (older adults, patients from marginalized neighborhoods). We will build a transfer optimization model that considers demographic, clinical and system factors to inform equitable and impactful inter-hospital patient transfers during future periods of hospital strain. Our results will help mitigate wider health consequences of hospital strain, promote equity, and increase the resilience of Canada's healthcare system.",2021,2023,Unity Health Toronto,394665.83,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19881,202107UIP,Understanding the Impact of COVID-19 on Children with Medical Complexity and their Families,"Children with medical complexity and their families are likely to be disproportionately impacted by COVID-19 and the unanticipated consequences of the pandemic public health measures on healthcare services, education, and social services. The health, education, and social lives of these children, and by extension their families, are shaped by a complex system of federal, provincial and local policies, as well as public health orders. Within the context of the pandemic, the needs of this population are at risk of being ignored, or worse, their rights being eroded. In this study, we will examine the lived experience of these families over time. We will recruit primary caregivers of children with medical complexity in British Columbia. We will collect data, through interviews and diaries. The information from these sources will help us identify factors that help or hinder families during the long-haul stage of the pandemic, and also the enduring impacts of public health measures from the earlier waves. We will share what we learn with other regions in Canada to inform and improve policies, clinical practices, and related supports for these families.",2021,2022,University of British Columbia,118400.46,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19882,202107UIP,Understanding the Impact of The COVID-19 Pandemic on Academic Achievement in Ontario- A Population-Based Cohort Study,"Education is one of the most important modifiable social determinants of health. Improving academic achievement has been associated with better overall long-term educational attainment. Greater educational attainment associates with better health (greater control of chronic illness, less obesity and improved diet), and longevity. The COVID-19 pandemic and school closures have disrupted primary and secondary education for Ontario students. The impact of the pandemic may have been worse among students facing sociodemographic barriers and educational needs. The objectives of this study are: 1) To provide novel information on the impacts of the COVID-19 pandemic on academic achievement among Ontario secondary students, and 2) To disseminate a novel, interactive, electronic platform for knowledge users (the Province of Ontario's Education Quality and Accountability Office (EQAO),educators, school board members), to share information on the impact of the COVID-19 pandemic on academic achievement. The platform will also be available to the general public. An integrated knowledge mobilization approach (iKMb) using population level data, in partnership with EQAO, will be conducted to achieve our research aims. As part of this approach, knowledge users will inform the project from start to finish. iKMb is the ideal approach in understanding and addressing the impacts of the COVID-19 pandemic on academic achievement; it gives the broader educational community the evidence to support the implementation of educational recommendations designed to mitigate the impact of the COVID-19 pandemic on Ontario students. Since education is among the most important modifiable determinants of health, understanding the impact of the COVID-19 pandemic on academic achievement is an important step in mitigating the impacts of the pandemic on children's future health.",2021,2022,Unity Health Toronto,118500,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19883,202111WI1,Understanding the Outcomes of Implementing Online HIV and COVID Self-Testing during the COVID-19 Pandemic: The GetaKit Study,"The COVID-19 pandemic highlighted the importance of public health services, specifically related to testing and contact tracing. The pandemic also highlighted limitations of healthcare service delivery during pandemics: such services were wholly depended on in-person services, despite safe, secure, and usable online services and at-home self-test devices. In response to this, I led a team of researchers and public health workers from the University of Ottawa, Ottawa Public Health, and the Ontario HIV Treatment Network to implement the 1st online HIV self-testing project in Canada (entitled 'GetaKit'). Through GetaKit, participants completed a self-assessment, including information about their demographics, and were deemed eligible (i.e., at-risk) for HIV or not. Those who were deemed eligible were offered a free self-test kit. All data (from the demographics, registration information, self-assessment, test eligibility, etc.) are recorded in our online GetaKit system and can be extracted for analysis. GetaKit has undergone two expansions since launching on July 20, 2020 in Ottawa only -- with a specific focus the HIV priority groups of gay, bisexual, and other men who have sex with men, persons who are trans, members of Indigenous communities, and persons who are of African, Caribbean, or Black ethnicities. The 1st of these expansions is that molecular COVID self-tests are available through GetaKit across Ontario as of October 14, 2021. Second, HIV self-testing is becoming available through GetaKit across Ontario. In the proposed study, we will analyze the data from GetaKit to address the following aims: 1.To quantify the impact of COVID-19 on HIV testing numbers, rates, and diagnoses in Ontario. 2. To determine if COVID-19 affected HIV testing numbers, rates, and diagnoses more profoundly among HIV priority groups, compared to the entire population in Ontario. 3. To identify the proportion of HIV testing that was done in Ottawa via GetaKit during COVID-19.",2021,2023,University of Ottawa,37498.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19884,202111WI2,"Understanding the Wider Health and Equity Impacts of Public Health COVID-19 Mitigation Strategies on Young Mothers, Children and Youth Living in Cities","The public health response to COVID-19 involved strategies to prevent person-to-person spread of the virus so that hospitals would not become overwhelmed with severely ill cases. These strategies included prolonged restrictions to social interaction, school and day care closures and substantial job loss in large sectors of the economy. There are concerns that disruptions to these social and economic activities could have profound health impacts in vulnerable populations. There is a growing recognition that urban life has important implications for health and that the built environment, neighborhood structure and social resources of cities can increase resilience or exacerbate inequities. This project will focus on measuring the broader impacts of COVID-19 public health containment strategies on a range of mental health , drug use and domestic violence outcomes in mothers of young children, children and youth that could be a product of the anxiety, depression, and a sense of hopelessness that is associated with loss of social interaction, education and employment that came with COVID-19 containment strategies. These outcomes will be measured using proven existing methods based on health system data, The study will draw on census data to measure important aspects of urban structure, labour force survey data to look at job loss, mobility data from cell phones to look at broad aspects of urban social interaction and publicly available data on urban school and day care closures. This study brings together a multi-disciplinary research team with extensive expertise in using these data. The results of this study on the association between public health mitigation and adverse outcomes mediated through urban structures and supports will help us to develop strategies to make cities more resilient and to inform our efforts to allow cities to recover from COVID-19 in a way that is fair and equitable and that serves the needs of children, youth, and mothers of young children.",2021,2023,University of Toronto,394439.89,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures | Health Systems Research",Research to inform ethical issues related to Public Health Measures | Indirect health impacts | Health service delivery,2021 +C19885,202108VCF,Understanding vaccine confidence and decision-making among Canadian youth: Survey and intervention development,"Chief Public Health Officer, Dr. Theresa Tam, recently called into action young people to receive the COVID-19 vaccine, stating they are less likely to ""offer their arm."" Canadian research conducted earlier in the pandemic (i.e., May-Dec, 2020) indicated that 35%-42% of youth ages 15-24 years reported being unsure or unwilling to receive the vaccine due to concerns about safety, efficacy, and a general lack of knowledge regarding vaccines. As of July 31, 2021, only 47% of 12-17-year-olds and 51% of 18-29-year-olds were fully vaccinated (73% and 70% at least one dose, respectively), demonstrating a need to understand and address vaccine confidence in this underrepresented population. To address this priority, we will first test a model of vaccine confidence in Canadian youth (ages 12-29 years) by answering the following questions: 1. What are the rates of vaccine acceptance among Canadian youth? 2. What are the key factors associated with COVID-19 vaccine acceptance and uptake among Canadian youth? 3. What factors are associated with COVID-19 vaccine acceptance and uptake among equity-seeking groups? Second, there has been limited information targeted towards youth, with most youth relying on parents or the internet to obtain health information, with this reliance associated with increased conspiracy beliefs and vaccine hesitancy in the literature. Social media and app-based methods have been shown to be appropriate for health messaging to young people. In collaboration with two youth advisories, we will co-develop, design, and disseminate a youth-focused app and social media ad campaign that aim to increase vaccine confidence among Canadian youth. Results will aid the public health response to the pandemic by generating high-quality information about drivers of vaccine hesitancy, and informing how to best approach fostering vaccine confidence among youth. Outputs will include youth targeted interventions developed by and for this underrepresented population.",2021,2023,University of Victoria,134559.91,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19886,202002OV4,"Understanding, Forecasting and Communicating Risk During the COVID-19 Epidemic","A new infectious disease, COVID-19, has emerged worldwide. Canada has experienced few cases, but there is great concern about the possibility of a Canadian COVID-19 epidemic. Canada has a history of preparing for and managing disease outbreaks caused by new viruses (SARS, H1N1, preparing for Ebola). For many people inside and outside the public health community, an important part of preparation is having access to accurate, timely, reliable information about how the disease is spread, who is at risk, and who is not at risk. Public health professionals often want the answers to three basic questions about epidemics: ""when will it peak?""; ""when will it end?""; ""how big will it be?"". Our team of doctors, epidemiologists, public health professionals, and statisticians has experience responding to past outbreaks like SARS, H1N1 and Ebola. We are already actively involved in analysis and modeling that is helping public health agencies and the general public understand the COVID-19 epidemic, and ""see what's around the corner"". We have proposed a three-part project, which will use math and statistical modeling to: (i) forecast the near-term course of the epidemic; (ii) gain better understanding of the parts of the epidemic that are hidden from view, by analysing data that are public, but often messy or noisy; and (iii) use our information to build simulations that can help guide Canadian health agencies as they try to control or limit the spread of COVID-19 in Canada. Throughout this project, we will be creating infographics and tools that let Canadians inside and outside the scientific community gain a better understanding of how epidemics spread, who is truly at risk, and what it takes to make epidemics end. By providing timely information to Canadians, we will help reduce the fear, xenophobia and anxiety that are often part and parcel of emerging infectious diseases.",2020,2022,University of Toronto,248762.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +C19887,202109EG3,Using behavioural science approaches to optimize Public Health and Social Measures (PHSM) that prevent COVID-19 transmission and infection in priority populations in diverse urban settings,"The WHO has identified Public Health and Social Measures (PHSM; e.g., physical distancing, mask-wearing, vaccination) as ""critical to limiting transmission of COVID-19 and reducing deaths."" PHSM remain vital given variants of concern that are more infectious and/or reduce vaccine effectiveness. It is still unclear what influences whether Canadians engage in PHSM behaviours, what enablers and barriers they face when engaging in them, what influences their long-term use and how these factors differ across specific groups especially historically excluded and equity-deserving groups. This hinders our ability to design tailored, behaviourally optimized, culturally appropriate programs to promote PHSM. We will address this by setting up a responsive, nimble and inclusive platform that will enable our knowledge users (public health units & community groups in 3 Ontario cities) to leverage behavioural science in ways that reflect their evolving priorities as the pandemic continues. We will generate a rapid understanding of what influences engaging in PHSM to create strategies to promote greater uptake and engagement in PHSM in ways that reflect the realities of priority groups in each city (including historically excluded and equity-deserving groups). We will work with our public health and citizen partners to recruit diverse samples that we will interview using a validated behavioural science framework. This will generate information about enablers/barriers to taking up and sustaining PHSM to enable tailoring to each group. We will investigate whether sex, gender, age, and other social identity factors modify enablers/barriers for each PHSM. The results will inform a) public health programs targeting sustained and effective PHSM to reduce risk of transmission and infection and b) management of future infectious disease outbreaks. We will conduct an arms-length evaluation of the behavioural science platform and its perceived value and impact for our knowledge user partners.",2021,2022,Ottawa Hospital Research Institute,241519.59,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Sexual and gender minorities | Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C19888,202112FO1,Using strengths-based Indigenous research methodologies to plan for current and future pandemics and health emergencies: Unpacking the complexity within Indigenous communities responding to displaced climate change refugees in central British Columbia during the COVID-19 pandemic.,"The Tl'etinqox and Qwelminte Secwepemc are experiencing the impacts of colonization and climate change on their land, waterways, foods, and medicines. They demonstrated their resilience to the catastrophic 2017 wildfires in Western Canada and were recognized as leaders in their cultural successes for protecting their land and communities from climate change. The Tl'etinqox and Qwelminte Secwepemc continue to respond to current climate change issues (wildfires, floods, landslides, and the resulting displacement of Indigenous community members from neighbouring Nations). However, the COVID-19 pandemic and the associated restrictions have exacerbated the impacts of climate change issues on the health and well-being of Indigenous peoples in these two cultural groups. By using Indigenous research methodologies (IRM) with a strengths-based approach, the proposed research aims to understand (1) the complex interplay between climate change, the COVID-19 pandemic, gender and intersectional perspectives, and health; (2) how this complexity has impacted Indigenous peoples' response to climate change refugees or evacuees; and (3) what sustainable community-led solutions might be suitable for the current and future pandemics and health emergencies. This will be done through the direction and engagement of Tl'etinqox and Qwelminte Secwepemc communities. Research capacity-building workshops will ensure that the Tl'etinqox and Qwelminte Secwepemc community members play a leadership role in designing and conducting the research, evaluating the outcomes, and disseminating the research findings in culturally appropriate ways. The communities will control how the information will be used, archived or shared. The Mataatua Declaration on Cultural and Intellectual Property Rights of Indigenous Peoples (1993), the United Nations Declaration on the Rights of Indigenous Peoples (2007), and the TRC recommendations (2015) will be honoured.",2021,2022,Thompson Rivers University,197500,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Other secondary impacts | Community engagement,2021 +C19889,202107UIP,Utilizing patient-centered and administrative data to uncover the COVID-19 pandemic's impact on adverse asthma outcomes in children,"Asthma affects 1 in 10 Canadian children. Typically, an annual peak in asthma flare-ups is observed in the fall months, with a smaller peak in the spring. There was a significant decrease in asthma-related emergency department (ED) visits and hospitalizations during the initial lockdown in spring 2020, likely due to the limited spread of respiratory viruses, a common asthma trigger in children, during the lockdown. However, our preliminary data show that with the relaxation of lockdown measures in spring 2021, there is a resurgence in the number of ED visits and hospitalizations. We hypothesize that respiratory viruses increased with the relaxation of lockdown measures, and that reduced access to healthcare services, reduced asthma medication adherence, and decrease physical activity during the pandemic could have led to poorly controlled asthma when relaxation of lockdown measures occurred, leading to a vulnerable period for asthma flare-ups. Our study's goal is to evaluate the impact of the COVID-19 pandemic on adverse asthma outcomes and to uncover the underlying mechanisms at the patient and population level. Having a better understanding of the trends in asthma flare-ups during/after the pandemic and the factors that influence these trends can help clinicians better manage childhood asthma during the rest of the pandemic and in the future. First, we will leverage an online platform built by our team to determine the associations between patient-related behaviors and asthma control, asthma-related ED visits and hospitalizations during and after the pandemic through electronic questionnaires. Second, we will use Canadian and provincial administrative databases to evaluate the impact of province-specific lockdown/lockdown-lifting measures and school closures/reopenings on asthma-related ED visits and hospitalizations.",2021,2022,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",118500,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19890,202108VCF,vACcine COnfidence amongst those living with alleRgy during the coviD pandemic (ACCORD): an integrated knowledge translation study,"The COVID-19 pandemic has impacted families worldwide. This impact is made worse by previously unseen amounts of time spent online, and the sheer amount of misinformation online. For people who live with allergic disease, reports of anaphylactic reactions to the COVID-19 vaccine have contributed to greater vaccine hesitancy. We are planning a project that will lower this hesitancy amongst people with allergic disease, and their healthcare providers. Our project has three goals. First, we will also speak with families with allergy about their concerns related to the vaccine hesitancy. Then, we will regularly review and update the literature on COVID-19 vaccines and allergic reactions. Finally, throughout the study, we will work with families and healthcare providers to widely share knowledge, in ways that are meaningful to those receiving the information. Our research questions are, ""What misinformation exists regarding the risk of COVID-19 vaccine-triggered anaphylaxis?"" and ""What methods and strategies are most appropriate, as determined by families and healthcare providers, to increase vaccine confidence?"" The primary outcomes for Objectives 1 and 2 include risk factors for anaphylaxis, and hesitancy related to the COVID-19 vaccine. The outcomes of Objective 3 include improved access to scientifically-robust information so that families and healthcare providers can make informed decisions. By engaging with families and healthcare providers throughout the project, and partnering with a not-for-profit organization that seeks to reduce the health literacy gap between families and healthcare providers, we will slow the spread of related misinformation and increase vaccine confidence.",2021,2023,University of Manitoba,158000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19891,202109EGB,Vaccine Distribution Approaches for Equity-Deserving and At-Risk Populations during COVID-19: Best Practices and Lessons Learned in Canada,"The World Health Organization has stated that one of the worst threats to overcoming COVID-19 is vaccine hesitancy. Vaccine hesitancy amongst underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution since it can result in poorer health outcomes, increased COVID incidence and less vaccination in underserved communities. Approaches for the effective distribution of vaccines for equity-seeking and at-risk individuals are urgently needed. This pan-Canadian study of British Columbia, Alberta, Manitoba, Ontario, Quebec, Nova Scotia, and Newfoundland will identify effective vaccine distribution approaches and advance knowledge on how to design and implement these approaches to meet the needs of communities and reduce the risk of health and social inequalities during and after COVID-19. An exploratory, multi-methods, case study design will be used to conduct a cross-case analysis of seven provinces in Canada. Each case will comprise of: (1) qualitative interviews with policymakers and public health officials; (2) quantitative data analysis of populations served by vaccine distribution approaches; and (3) focus groups with regional stakeholders, providers, patients, and caregivers within effective vaccine distribution models. A thematic analysis of interviews and quantitative data analysis will help identify effective approaches. Focus groups with equity-deserving individuals, caregivers, healthcare providers and other key informants will identify the factors (provincial/federal, structural, community, family, personal) that were enablers or barriers to implementing vaccine distribution programs. A cross-case-study analysis will be done to identify similarities and differences. The outcome of this study will be recommendations for the implementation of equitable and effective vaccine distribution approach(es) in Canada.",2021,2022,University of Toronto,390036.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19892,202005VR1,"Vaccine efficacy in nonhuman primates against SARS-CoV-2: protection, cross-protection and immune enhancement","In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. Since then (in only the last 5 months) this virus, has caused a global pandemic resulting in 4.2 million cases and over 288,000 deaths. Quarantine measures have not been sufficient to interrupt transmission despite near world-wide unprecedented disruptions of normal activities. Since its identification we have been working on making a vaccine to prevent infection with SARS-CoV-2. This vaccine contains a portion of the spike protein (the protein that is present on the surface of the virus) and when delivered to animals, induces an immune response. So far, we have shown that this vaccine can cause an immune response in ferrets, and early data suggests that to is also protective. To ensure that this vaccine is safe, immunogenic and effective we propose to test it in a nonhuman primate model of SARS-CoV-2. Typically nonhuman primates are the animal model that most closely resembles what happens in humans. To do this rapidly, we will vaccinated animals at the National Microbiology Laboratory with our vaccine to determine whether it induces the kind of immune response we want to see. Namely, whether it induces antibodies that are capable of blocking infection - called neutralizing antibodies. Finally, we want to demonstrate that this vaccine actually protects the animals from infection and does not cause any deleterious events, so animals will be infected and monitored to determine whether the vaccine stops infection. Subsequent experiments to support this data will be performed at VIDO-InterVac. Together this work will increase the capacity to assess other vaccine concepts that are being worked on across Canada to identify the best approach to stop transmission of SARS-CoV-2.",2020,2021,University of Saskatchewan,1094493.75,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +C19893,202111WI1,Virtual Innovation for Stroke Investigation and Treatment during COVID19 across Canada (VISIT-Canada),"Every 9 minutes, someone in Canada experiences a stroke. Stroke is the third most common cause of death among Canadians. The COVID19 pandemic has affected stroke care in many ways. First, infection with the coronavirus is associated with an increased risk of stroke. Second, the pandemic-related restrictions could affect people's ability to renew their regular medications on time, including those that are important for stroke prevention like blood thinners or medications to control blood pressure, diabetes, or cholesterol. Third, despite the new and widespread use of telemedicine for doctor visits since the beginning of the pandemic, it is not clear if all regular care after a stroke can be maintained through video or telephone calls. Certain patients may be particularly vulnerable to difficulties with telemedicine, including those who are older, women, those who experience socioeconomic deprivation, or who live in rural regions. These are the questions we are proposing to study. Given COVID19 has affected Canadian provinces differently, we will be studying the stroke care and outcomes in Alberta, Ontario, and Nova Scotia. We will use routinely collected administrative health data in this study. In each province, we will make comparisons before and after the pandemic. We will 1) evaluate whether the number of stroke hospitalizations has increased, 2) report whether Canadians are more likely to have interruptions in their medications, and 3) study the uptake of telemedicine visits after stroke and how patients with stroke are faring. Our research team will be working closely with provincial and national policymakers and stroke organizations. This study will help the health system prepare for any anticipated increase in stroke cases in Canada and plan for the optimal delivery of health care to ensure excellent and equitable stroke care and prevention.",2021,2023,"Sunnybrook Research Institute (Toronto, Ontario)",317092.57,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19894,202109EG6,Virtual physical rehabilitation following COVID-19 hospitalization,"The consequences of COVID-19 can be serious for many people, especially for those who are older and have health conditions. Some patients may need to be in hospital and even be admitted in the intensive care unit. Emerging data on the long-term consequences after COVID-19 suggests that many patients suffer from persistent symptoms including mobility problems, breathlessness, and fatigue. Preliminary data from our group shows that at 12-month post-discharge, 46% of patients report important problems in mobility. This emerging data suggests that these patients will likely benefit from a rehabilitation intervention. This approach is actually recommended by the World Health Organization and international respiratory societies. To date, there is very limited evidence to support and detail the benefits of rehabilitation programs in COVID-19 patients who needed to be in the hospital. We will test a virtual rehabilitation program for patients who have been in the hospital because of COVID-19. Patients will be recruited from the COVID-19 clinic of the McGill University Health Centre and from a longitudinal study of patients with COVID-19 from McMaster University. Participants will be divided into two groups. One group will receive an 8-week home-based virtual rehabilitation program consisted of exercises and education plus usual care. The other group will receive usual care which will include education on how to manage symptoms and engage in physical activity. We would like to investigate if our virtual rehabilitation program can improve patients' mobility, physical function, quality of life and mental health. If we prove our rehabilitation program to be effective, this model of care can be implemented nationally and internationally and benefit hundreds of patients worldwide.",2021,2022,Research Institute of the McGill University Health Centre,350323.92,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +C19895,202005VR5,Wastewater surveillance of SARS-COV2 to enable real-time clinical case-finding in Calgary,"We propose to track SARS-COV2 in the wastewater (WW; i.e., sewage) in Calgary, Alberta. The SARS-COV2 virus is excreted in the poop of infected individuals - often before symptoms start. These viruses are no longer infectious, but their genetic material (RNA genomes) can be detected in wastewater samples using molecular biology techniques for RNA quantification. This project will create a pathway enabling mobilized testing of the WW network throughout Calgary. Our project will achieve 3 objectives: 1 develop procedures to collect and analyse SARS-COV2 genetic material in WW samples from regionally diverse parts of Calgary, 2 develop different molecular assays that complement each other and are resilient to the WW chemical matrix, 3 develop genomics and bioinformatics methods for identifying genetic variants of SARS-COV2 in Calgary WW thereby enhancing epidemiological tracking. In Stage 1 we will develop and validate assays with samples from Calgary's three WW treatment plants, accounting for variability in WW chemistry and its effect on molecular biology methods. In Stage 2 we will work closely with Alberta Health Services and City engineers to apply the assays on WW from areas with known active COVID-19 cases to demonstrate proof of principle. In stage 3 we will deploy in real-time sampling teams through the city to collect samples for monitoring new areas where infections are not known to exist, allowing AHS to proactively find and respond to infected people without symptoms. Our team involves AHS, the City of Calgary, engineers, microbiologists, clinicians/public health experts, and University deans from Science, Engineering and Medicine. We will provide real-time, actionable information on SARS-COV2 in Calgary enabling public health officials to perform regionalized case-finding and develop strategies that focus containment efforts in the areas most affected, while minimizing the collateral social and economic consequences of needed public health interventions.",2020,2021,University of Calgary,378982.5,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen | Impact/ effectiveness of control measures",2020 +C19896,202111WI2,What are the long-term health and labour market outcomes of workers who experienced work-related COVID-19 transmission?,"The COVID-19 pandemic has caused massive disruptions to the Canadian workforce. Key among these disruptions are the health and work impacts of COVID-19 on workers who acquired their COVID-19 infection during the course of their employment, often providing essential services. For example, in Ontario there have been almost 28,000 accepted workers' compensation claims for COVID-19, and more than 32,000 cases attributed to workplace outbreaks. It is important to understand what the long-term health and employment outcomes are amongst workers who acquired COVID-19 through workplace exposures. Canadians who have acquired COVID-19 at work likely experience unique circumstances that could influence how well they recover physically, how they fare emotionally, and their process of returning to the workplace where their infection occurred. To better understand these impacts in this study we will collect survey data to estimate the prevalence of depression, anxiety, physical function, and self-rated health among these workers, as well as documenting if they are back at work, and working in the same occupation. We will conduct surveys approximately 18 months after the initial COVID-19 absence. We will compare these experiences with other workers who had a workers' compensation claim around the same time, but where the injury and illness was not related to COVID-19. Findings from this project will provide a much needed knowledge base for workplaces and workers' compensation agencies to better understand and address the impacts of COVID-19 among workers in Canada.",2021,2023,Institute for Work & Health (Toronto),325587.44,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2021 +C19897,202111WI1,What are the wider health impacts of COVID-19 on fracture patients served through Ontario's province-wide Fracture Screening and Prevention Program?,"A fragility fracture happens after a slip, trip, or fall from standing height or less (e.g. slipping on ice and breaking a wrist). Over 131,000 Canadians have one of these fractures every year. This type of fracture predicts future fractures, such as devastating hip fractures, and is a sign of poor bone health that requires treatment. Fractures generally happen in women and older individuals with other chronic health conditions. The Fracture Screening and Prevention Program is a program that runs in 34 Ontario fracture clinics. Through the program, coordinators see about 8,000 patients per year. They arrange for patients to get a bone mineral density test, referral to a specialist, and treatment that may include medication. COVID has disrupted fracture patients' access to health care worldwide but little is known how it has affected Canadian fracture patients. Our goal is to determine how COVID has affected fracture patients in Ontario. We will analyze data from the Fracture Screening and Prevention Program to see how COVID has affected patients' access to testing, specialists, and treatment. We will also interview coordinators who work in the fracture clinics to ask about their experiences with helping patients in the program. Finally, we will interview patients from fracture clinics in the program to ask them about their experiences with their fracture and their bone health, such as getting to specialist appointments. Our research will inform the development of interventions to help fracture patients during a pandemic like COVID. For example, we might offer virtual visits with a specialist or pharmacist to talk with patients about the prescribed medication. It is important that fracture patients follow bone health treatment recommendations because treatment can prevent future fractures like a hip fracture. This will help decrease health care costs in Canada related to fractures, including admission to hospital, extended care facilities, and nursing homes.",2021,2023,Unity Health Toronto,275707.63,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19898,202109EG7,When Crisis Meets Opportunity: Responding to COVID-19 with integrative health and sheltering models for persons experiencing homelessness,"What is the issue? COVID-19 has disproportionately impacted individuals experiencing homelessness in Canada. In response, several regions have adopted programs that integrate non-congregate shelter (e.g., motels), with on-site health care and other supports. In addition to stopping the spread of COVID-19, these programs have shown improved outcomes when compared to the standard congregate shelter program, including reduced 911 calls, fewer overdoses, and increased permanent housing. Understanding how these programs were implemented may allow for their continuation and expansion beyond the pandemic. What is the overall goal? We will work with community partners to examine initiatives in two mid-sized Ontario cities that have adopted integrated health and non-congregate sheltering models during COVID-19. We will learn how the programs were implemented, what resources are required, and what would be needed to sustain the programs post-pandemic. We will interview program staff members (including healthcare providers, shelter workers, and administrative staff) and clients to learn about their experiences implementing the program and will examine program documentation such as meeting minutes, reports, policies and budgets to better understand the process, planning, costs and policies that are associated with the program. We will use all of the information gathered to create a guide to share with other regions interested in developing and implementing a similar model. What is the expected impact? Our project will yield an in-depth understanding of integrative health and sheltering programs developed in response to the pandemic and will learn how these programs can be successfully implemented and sustained.",2021,2022,London Health Sciences Centre Res. Inc. (Ont.),144074.67,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19899,202203MM1,When the Helpers Need Help: Barriers to Care and Longitudinal Mental Health Outcomes Among Public Safety Personnel,"People working as public safety personnel (PSP; e.g., firefighters, paramedics, police, corrections officers) experience many traumatic events on the job. As a result, posttraumatic stress injuries (PTSI) such as posttraumatic stress disorder, depression, and anxiety, have also been found to be higher in PSP than in the general population. Most research in this area has relied on self-report questionnaires instead of measuring mental disorders using clinical diagnoses, has not looked at the mental health of PSP over time, and has rarely looked into the reasons why these individuals would not obtain mental healthcare or use coping strategies that might help prevent the development of a mental health problem. The proposed research will address these gaps by combining information from administrative health records with the collection of a new survey of two groups of PSP - firefighters and paramedics (FP) - in Winnipeg, Manitoba: Aim 1) Determine the FP who were diagnosed with a mental or substance use disorder, had a suicide attempt, or had a mental health-related Workers Compensation claim, and compare these numbers to a group of non-FP adults and to mental disorders in FP pre-COVID-19. Aim 2) Look at potential protective factors for mental disorders in FP, compared to a group of employed Winnipeg residents. Aim 3) Measure the amount of mental healthcare use among FP in the past year compared to a cohort of employed Winnipeg residents and identify barriers to care. This study will provide new information about the extent of mental disorders in FP, and therefore, can be used to advocate for more mental health resources for this population. Findings will also help the development of new programs and strategies to overcome the most common barriers to seeking mental healthcare in this population.",2022,2024,University of Manitoba,100138.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C19900,202203MM1,WHERE Study: Waiting for Hip or knEe REplacement: A prospective cohort,"Total hip and knee replacements (TJR) for osteoarthritis are common orthopaedic procedures performed in Canada. Waits for these procedures are already lengthy, and the COVID-19 pandemic has further delayed thousands of scheduled TJRs. Longer wait times for TJR can be associated with increased pain and functional disability, and up to 80% of patients awaiting TJR use opioids for pain management. Further, some studies show that certain minority or disadvantaged groups may be more likely to wait longer and report worse pre-operative symptoms. Moreover, worse pre-operative symptoms and opioid use have been linked to poor recovery and continued opioid abuse post-operatively. Interestingly, some clinical studies have shown that not all patients experience a deterioration in symptoms while on the waitlist for TJR, and a longer wait time is not always associated with poor post-operative outcomes. However, there is insufficient evidence surrounding the relationships between wait time, patient characteristics, and outcomes both prior to and following TJR. We aim to establish a large prospective cohort of patients with osteoarthritis waiting for TJR with key research questions and the overarching objectives of identifying which patients are most affected by longer waits, and which patients may tolerate longer wait times. We will enroll 2,070 patients awaiting TJR in Ontario, Canada, and follow the patients from their waitlist enrolment up to two years post-operatively. During this time, we will collect pain, function, opioid use, and quality of life measures at regular intervals. In addition, we will conduct an economic analysis to determine the impact of length of time on a waitlist on patient and healthcare system costs, and whether this varies for certain subgroups of patients. The data will highlight the consequences of long waits for patients undergoing TJR, information that will improve patient care and provide insight for refining wait list policies.",2022,2024,London Health Sciences Centre Res. Inc. (Ont.),294525,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery | Health financing,2022 +C19901,202111WI2,Why have suicide rates not increased during the pandemic? An interrupted time series of suicides in Ontario to examine changes in demographics and methods during the pandemic; an interrupted time series analysis and descriptive study of suicides looking at the effects of states of emergencies on suicides; and a mixed methods study of people who survive opioid overdoses to examine whether suicide deaths have been displaced into opioid overdose deaths.,"Contrary to predictions at the start of the COVID-19 pandemic suicide rates have not increased and may have declined during the pandemic. However, some sub-populations may have had an increase in rates which is hidden in the general population figures. Possible explanations for the absence of an increase in suicides include a paradoxical increase in social support ""everyone pulling together"" and a shift from suicide deaths to deaths by opioid overdoses. We propose two research streams to examine these hypotheses. The first research stream will focus on suicides in the general population which addresses the extent and impact of COVID-19 and the resilience of people of Canada. We plan to do an analysis of suicide deaths from Ontario coroners' records of suicides from 2015 to February 2020 compared to suicides after March 2020 to detect any changes in demographics and suicide methods. Second, we will compare the number and circumstances of suicides during Ontario's states of emergency during the pandemic to times during the pandemic when these states were not in place. These two studies should answer questions about the effect of the pandemic on suicides in different sub-populations and the influence of social isolation. This will identify the effects of policy decisions around lockdown interventions in future health emergencies and pandemics. The second research stream will address whether some suicides have been shifted into the opioid using population. This will generate evidence related to the marginalised population of drug users and the effect of the pandemic on exacerbated substance use. We will do a qualitative study of drug users who have survived an opioid overdose to assess whether the overdose was a result of suicidal thoughts and to ask what could have made their drug use safer. Second, we will identify people who have survived opioid overdoses before and during the pandemic to examine differences in mental health morbidity and mortality.",2021,2023,Ottawa Hospital Research Institute,394910.73,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19902,202111WI1,Wider Health Impacts of COVID-19 on Patients with Cancer and Other Multiple Chronic Conditions: A Parallel Mixed-Methods Study,"The wider effects of the COVID-19 pandemic on the health systems and non-COVID patients only start to be understood. Patients with cancer and other multiple chronic conditions (MCC) are particularly at risk of long-term negative health consequences. Real-world evidence and evaluation on cancer care remains scarce despite a rising number of simulation and modelling studies. Multimorbidity has comparatively received much less attention. Yet, about 25% of the population are living with MCC, and the burden of multimorbidity was already on the rise before the pandemic. Our project aims to measure the potential impact of COVID-19 on patients with cancer and MCC and to identify models of care and innovative interventions that could mitigate these impacts. We will focus on Ontario, the most populous province and severely affected by the first three waves of the pandemic. We adopt a parallel mixed-methods design where we will quantitatively assess the wider effects on the evolution of cancer care trajectory and severity for patients with MCC, and whether some models of care have mitigated these effects better than others; and qualitatively reveal the experiences of these patients, their family, and their clinicians, and identify changes to practice that may have limited the impacts of the pandemic. Results from this project will significantly advance knowledge on the actual (rather than forecasted) impact of COVID-19 on a large group of Canadians particularly at risk of health deterioration, and often marginalized. Deliberative dialogues engaging research, clinical, policy and patient partners in Ontario and other provinces (e.g., British Columbia, Quebec), will be used to maximize transferability of our findings and opportunities for scaling-up mitigation strategies across Canada. Our findings will provide information to feed in new mathematical modelling to improve preparedness for future health emergencies, and a foundation for future multi-jurisdictional studies.",2021,2023,Carleton University (Ottawa),393578,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C19903,202111WI2,Wider Impacts of the COVID-19 Pandemic on the Health and Well-Being of Pregnant and Parenting Youth and their Children in Canada.,"COVID-19 pandemic has disrupted the normal life and routine of all individuals. Youth (15-24 years) are at low risk for hospitalization and death from COVID-19. However, evidence suggests that the disease affected other aspects of their physical, mental and social health. Pregnant and parenting youth and their children are especially affected by the closure of social spaces, including schools, community centres, and health clinics, where many of them receive social support and healthcare for themselves and their children. In many places, health facilities have closed or have limited the available services. In addition, they may be unable to visit health facilities because of movement restrictions or because of fears of COVID-19 exposure. To the best of our knowledge, no research investigated the wider and long-term consequences of COVID-19 on pregnant and parenting youth and their children in Canada. To address this gap, we will explore the perspectives of pregnant and parenting youth (mother and father) on how the pandemic has affected their own and their children health and wellbeing and propose effective interventions to mitigate the challenges faced by young parents to be better prepared for future health emergencies and pandemics. This project will be conducted in 2 phases: Phase 1: Qualitative individual interviews with pregnant and parenting youth (of all genders) and service providers to investigate the impact of the COVID-19 pandemic on their own and their children's mental, physical, and social wellbeing. Phase 2: Develop pandemic response framework and strategies (i.e. toolkits) that support pregnant, parenting youth and their children better health and well-being. This research will provide essential information to inform current and future policies, support services, and programming, to improve the support services for pregnant and parenting youth and their children with special reference to the incidence and impact of the COVID-19 pandemic.",2021,2023,University of Alberta,243714.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C19904,202111WI2,"Working in the time of COVID-19: Exploring the effect of COVID-19 policies on violence, bullying and harassment in the service sector in British Columbia","The COVID-19 pandemic has exacerbated many work-related inequities with essential workers having to work at considerable risk in environments where there is COVID-19 exposure. In British Columbia, the restaurant and hospitality sectors have remained open throughout most of the pandemic with reduced hours, masking and restricted capacity. In August 2021, by order of the public health officer, patrons of licensed restaurants, pubs and other establishments were required to show proof of vaccination with a first dose by September 13 and a second by October 24. Businesses were required to check for vaccination status and deny services to those not meeting this requirement. Women, racialized persons and youth are overrepresented in the accommodation and food service sector and in lower paying positions and are at high risk of harassment and violence at work. Workers are often precariously employed and are at a power disadvantage with employers and customers. Growing evidence suggests that COVID-19 working conditions, including the requirement to enforce COVID-19 workplace safety protocols, puts these workers at a greater risk for harassment and violence as well consequent negative physical and mental health outcomes. This project is a mixed-method study that has three aims: First, it will conduct key informant interviews in the restaurant and hospitality sector to understand the experience of violence and harassment working under COVID-19 restrictions. Second, a survey of restaurant and hospitality workers from the Metro Vancouver and Central Okanagan regions who have experienced violence or harassment will be conducted to understand the broader contexts and the determinants and outcomes of their experience. Third, facilitated work will be conducted with community-based organizations, employer and worker associations, and WorkSafeBC to develop recommendations and guidelines to prevent and mitigate harassment and violence in the workplace due to public health measures.",2021,2023,University of British Columbia,385207.16,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C19905,202108VCF,Youth in a pandemic: A youth-led photovoice exploration of COVID-19 vaccine confidence,"Youth have been uniquely affected by the COVID-19 pandemic. Despite high rates of infection among youth, they have only become eligible for vaccination later in the vaccine rollout, and may be more hesitant to be vaccinated. Empowering youth to make informed choices about their health is key to public health equity. Photovoice is a research method that engages participants in understanding their world through an arts-based approach. Participants create knowledge through their real-world lived experience and expertise, using photography to represent their understanding of an issue. Photovoice has been shown to improve health knowledge and to empower marginalized populations. We propose a youth-led photovoice project that will solicit critical perspectives on COVID-19 confidence and hesitancy. From a SPOR approach, youth will lead the project, including a youth research assistant supported by a youth project steering committee, with support from experienced researchers. Thirty-five youth from across Canada will participate in a series of supported activities in which they will take photos representing their perspectives on COVID-19 vaccine confidence. We will then hold focus group discussions with them to understand the perspectives that emerged through the photovoice activities and to record critical dialog on COVID-19 vaccine confidence from the perspectives of Canadian youth. Knowledge mobilization activities will include conventional academic outputs (papers, conference presentations), government-focus reports, virtual photography galas, an online gallery, a virtual art sale, press releases, and social media campaigns. Together, these activities will ensure that the findings reach a variety of relevant stakeholders, including youth, the broader community, the media, government, youth-serving organizations, and policymakers.",2021,2023,Centre for Addiction and Mental Health (Toronto),155432.5,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C19906,202107UIP,Youth mental health and COVID-19: Longitudinal trajectories and youth-generated recommendations for Canada's recovery and future planning,"Youth have experienced substantial impacts from the COVID-19 pandemic and related public health measures. These include impacts on their schooling, jobs, relationships, services, emerging independence, and mental health. This proposal extends our work on COVID-19 and youth and emerges directly from discussion with our youth co-researchers. We propose three research activities: 1)Youth mental health survey extension. We have been surveying youth every two months since April 2020. Under this funding, we will survey them two more times, i.e., at six months and 12 months after the last survey we conducted under the previous funding. Together, this will provide a 2.5 year picture of youth MHSU and other COVID-19 impacts, among youth with previous MHSU concerns and youth without. 2)Youth consensus statement on a pandemic recovery strategy. Youth will generate concrete, implementation-ready recommendations for policymakers to ensure that Canada's recovery from COVID-19 will support youth MHSU, economic and educational recovery for youth, and holistic wellness across life domains. 3)Youth consensus statement on response strategies for the next pandemic. This project, identified as a top priority by our youth co-researchers, will develop youth-derived recommendations that will equip policymakers to respond more effectively to the next pandemic or public health emergency. As COVID-19 case counts decline and our hopes rise that Canada may be entering its recovery from the pandemic, the country will soon embark on a new phase of decision-making and planning. This project ensures that governments, policymakers, and decision-makers will have direct access to recommendations co-developed with youth to support youth-oriented, population-based decisions for Canada's recovery from COVID-19.",2021,2022,Centre for Addiction and Mental Health (Toronto),118500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2021 +C20286,Unknown,Real-time evaluation of the deployment of connected technologies and the partnership of care and services in the context of the health crisis linked to COVID-19 - the Techno-COVID-Partnership program,"Google translate: Faced with an unprecedented health crisis, the two establishments that receive the most patients with COVID-19 in Quebec have decided to implement social and technological innovations adapted to each stage of the trajectory of patients with COVID-19. COVID-19, from diagnosis to cure, in order to reduce isolation, maintain the partnership between patients and clinicians and promote the quality and safety of care. Grouped within the Techno-COVID-Partnership project, this research makes it possible to evaluate in real care situations, how these innovations are implemented, on what dimensions they act and how much they can cost as well as to determine if factors can explain certain results. The innovations studied relate to (i) the contribution of mobile applications for maintaining newly diagnosed patients; (ii) the combination of telephone calls from volunteers to break the isolation and the use of different technologies to carry out teleconsultations and remote monitoring; (iii) the adoption of a companion robot to entertain and care for COVID-19 patients hospitalized with psychiatric disorders; and (iv) support for patients during their transition and return home through COVID-19 support patients and a remote monitoring platform. The evaluation of these innovations is a unique opportunity to show how virtual health tools can potentially reliably treat thousands of patients over a short period of time while preserving health personnel at risk and ensuring the maintenance of social ties and the partnership. If the results are conclusive, they will make it possible to accelerate their implementation in other establishments (Canadian and international), not only for COVID-19 but also for any other health problem that can benefit from these technologies and modalities.]",2020,-99,Centre hospitalier de l'Université de Montréal,376865.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Social impacts",2020 +C20287,Unknown,Gender and addiction intervention in the context of a pandemic with people in socially precarious situations,"Google translate: This knowledge synthesis aims to guide the improvement of addiction practices in the context of a pandemic, taking into account an analysis based on sex and gender relating to the various social and health needs of people in socially precarious situations. Individuals in socially precarious situations facing problematic substance use face increased risks with respect to COVID-19 compared to the general population. Often struggling with chronic health conditions, these people are particularly at risk of facing serious consequences if they become infected, while health instructions tend to be more difficult to apply to their living environment. The experience of a pandemic can contribute to triggering or aggravating a psychosocial crisis in these people who already face co-occurring mental disorders. The WHO points out that the social consequences of COVID-19 hit women even harder (economic precariousness, single parenthood, violence, barriers to access to services, etc.). A scoping review will examine best practice guides and evaluative studies to identify gender-responsive addiction interventions that can be recommended for people in social precariousness in the context of COVID-19. Also, approximately 30 individual interviews of 45 to 60 minutes will be conducted with key players in Quebec who have professional expertise or experiential knowledge on the subject of study (decision makers, practitioners and drug users). The knowledge synthesis will make it possible to integrate the results of these two components in order to guide the co-production of recommendations with the team of this project, which integrates researchers and users of knowledge from the fields of addiction and public health.]",2020,-99,Université de Sherbrooke,37460.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20288,Unknown,Immunogenicity of a mucosal vaccine against SARS-CoV2 responsible for covid-19,"Google translate: With the current pandemic and the urgency of finding effective treatments to control the progression of the disease, a race has begun to develop an effective vaccine against the virus responsible for Covid-19. Although the development of a vaccine takes a long time, the fact remains that vaccination remains the best means of protecting the population in the medium and long term and curbing the resurgence of the disease. Several approaches are proposed for the development of this vaccine, each with its advantages and disadvantages. However, the multitude of proposed approaches will ensure that a vaccine candidate will eventually give convincing results. This project aims to demonstrate the concept of one of these vaccine approaches. The project proposes to use probiotic bacteria modified to express the major protein of the virus in order to use them as immunization vectors through the oral or nasal mucous membranes. This approach, which has already been used experimentally to design other vaccines, offers the advantage of creating immunity at the main entry point of the virus: the respiratory tract. this approach should facilitate their registration with regulatory agencies. If they prove conclusive, the results of this preliminary study open the door to efficacy studies and the continuation of this approach in order to come up with a solution to control this infection.]",2020,-99,Cégep de Lévis-Lauzon,56250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C20289,Unknown,Inoculating Against an Infodemic: Microlearning Interventions to Address COVID-19 Misinformation,"The effort seeks to improve personal health and the health of populations by combating misinformation and developing online learning interventions that improve people's knowledge, skills, beliefs, and behaviours related to COVID-19. In particular, the effort uses a design thinking approach to (1) examine digital misinformation flows pertaining to the outbreak; (2) develop, test, and improve educational interventions to reduce the spread of online misinformation. The outcomes of the project will be: (1) the creation of effective COVID-19 educational interventions; (2) the provision of health-related information recommendations and resources to guide non-profits and other community groups who wish to educate the public; (3) the development of increased individual and community capacity to identify the differences between trustworthy and untrustworthy information on the virus; and (4) the mitigation of misinformation related to COVID-19. To reach these outcomes, we will rapidly develop and deploy COVID-19 educational interventions in a variety of cultural contexts. We will test and improve these interventions based on empirical data from a variety of sources including focus groups, surveys, social media, and field research. Instruments, data, and resources will be shared on an interactive website with licenses that allow others to reuse them for free.",2020,-99,Royal Roads University,358262.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication,2020 +C20290,Unknown,"Digital Interventions to Detect, Prevent and Manage Mental Health Problems in People with Chronic Conditions: Knowledge Synthesis","Google translate: The global COVID-19 pandemic is affecting the majority of countries and has caused hundreds of thousands of deaths so far. Considered a humanitarian disaster, it will have serious impacts on the mental health of the population, especially the most vulnerable groups, including people with chronic illnesses. These individuals are at greater risk of presenting mental health problems such as anxiety and depression, risks increased by the loss of social support and loneliness. If left untreated, these problems can have long-term consequences on people's health and increase the costs associated with their treatment. Scientific studies have demonstrated the effectiveness of first-line interventions in improving the management of mental health problems in people living with chronic illnesses. However, there is little knowledge about interventions that use digital technologies. In the context of the current crisis, these technologies can be a relevant solution to better reach people living with chronic diseases and intervene with them. Our project will verify whether there are effective digital health interventions to prevent, detect and manage mental health problems in people living with chronic illnesses. First, we will consult documents that summarize the results of research on the subject. Next, we will summarize the knowledge identified and share it with team partners. Finally, we will do further research in the scientific literature in order to answer the partners' questions as effectively as possible. This project will make it possible to develop digital health solutions for optimal monitoring of mental health problems in people with chronic diseases, adapting to the context of the COVID-19 crisis.]",2020,-99,Université Laval,37494,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20291,Unknown,The reorganization of institutional and community services for people experiencing homelessness and the needs of people experiencing homelessness to deal with the COVID-19 pandemic,"Google translate: Considering the containment measures adopted by the government, the restrictions in terms of gathering and movement, the closure of public spaces but also private spaces of a public nature such as shops, shopping centers, libraries, etc., the reality of people experiencing homelessness (PSI) has changed profoundly in recent weeks, as have intervention practices in this field. However, few studies are interested in understanding the impacts on organizations, services, stakeholders and the people concerned, as well as the mechanisms and adaptation strategies put in place. The objective of this study is therefore to understand this resilience of organizations, institutional and community stakeholders and people experiencing homelessness. By observing and comparing in the different regions of Quebec, the adaptations, the transformations put in place as well as the resistance encountered to respond to this pandemic, the project aims to document and circulate the responses offered in terms of intervention in the field of homelessness, the impacts of COVID on workers and their practices in different intervention settings and on ISPs in their routines and their needs by contrasting on the dimensions of sex, gender, sexual orientation, age, type of homelessness experienced and associated personal difficulties, in particular mental health and drug use) Through the creation of a Homelessness-COVID19 Observatory, this study aims to produce analyzes focused on the use of the results by professionals and decision-makers, and a transfer of knowledge oriented towards sharing lessons learned here to better support elsewhere in order to support and strengthen the resilience bond of all in the context of this pandemic.]",2020,-99,Université de Montréal,154695.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20292,Unknown,Mindfulness to Combat Health Care Worker Burnout during COVID-19: Evaluating a 4-week tailored program.,"During the COVID-19 pandemic, health care workers are susceptible to virus exposure, increased workload, and moral dilemmas. As such, these essential workers are at risk for burnout. Establishing an effectiveintervention for health care workers to reduce burnout is a critical challenge faced by hospitals, includingWaypoint Centre for Mental Health Care, amidst the COVID-19 pandemic. Mindfulness programs are known to decrease physician burnout. However, to our knowledge, this proposed research is the first to evaluate the efficacy of online mindfulness interventions for health care workers, as well as long-term maintenance effects. To-date, face-to-face delivery has been the favoured instructional method for mindfulness programs. WithCOVID-19 rendering in-person delivery impossible, Waypoint would deliver this program virtually.Specifically, leveraging its current face-to-face- mindfulness program, Waypoint will implement a 4-weekonline mindfulness training program adapted from the Mindfulness Without Borders (MWB), MindfulnessAmbassador Program, an evidence-based curriculum, rooted in social and emotional development. The online program will be delivered by certified Waypoint facilitators, and open to all health care workers across theNorth Simcoe Muskoka area. Georgian College's Department of Research and Innovation will leverage itsdeveloped network of researchers to lead and support this project. Collaboratively, with Waypoint, researchers will examine the efficacy of the 4-week online program on mitigating burnout in health care workers andenhancing resilience, plus quantify the long-term effects in health care workers. Knowledge gained will beshared with health care leaders tasked with combatting burnout during a pandemic, and guide the delivery of wellbeing programs in the broader community. Findings will help combat COVID-19-related burnout andmental health issues, as well as springboard development of an online curriculum that can be deliveredremotely and safely during a pandemic to health care workers.",2020,-99,Georgian College,56250,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C20293,Unknown,Implementation of public health measures for vulnerable populations during the COVID-19 pandemic in French-speaking African countries in conflict: Case study in Mali and Burkina Faso,"Google translate: The first case of COVID-19 in Africa was confirmed on February 14, 2020, and within weeks the virus had spread to all countries. The impact of the COVID-19 pandemic could be devastating in African countries, especially those weakened by conflict, which host thousands of refugees, internally displaced persons (IDPs) and migrants. In the absence of treatments or vaccines, governments and humanitarian actors have implemented public health measures to slow the spread of the virus. In Mali and Burkina Faso, these measures include isolation of COVID-19 patients and home quarantine of suspected cases. Social distancing and containment measures are also being implemented to mitigate the pandemic. For IDPs and migrants, the implementation of these measures is more difficult due to the crowded and unhygienic conditions in which they live. In addition, many people are not aware of the existence of these directives, do not understand them or are not convinced of their importance. This research will provide a better understanding of the challenges facing authorities and humanitarian actors in implementing public health measures in response to COVID-19, as well as the difficulties that IDPs and migrants face in adopting these measures. . It will study the relevance of each measure in relation to the specific context in which IDPs and migrants live and will propose appropriate adjustments. Our results will help identify best practices and offer assistance tailored to the needs of IDPs and migrants so that they can better apply social distancing and confinement measures. Our results may contribute to increasing the adaptation of public health measures in other contexts, in order to slow down epidemics in general.]",2020,-99,Université Laval,83613,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa,,,,Canada,Mali | Burkina Faso,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +C20294,Unknown,Nutrition as Medicine: from research to implementation,"Google translate: Malnutrition and weight loss are endemic in long-term care facilities (LTCFs). Yet their consequences are serious, including an increased risk of mortality and morbidity such as pressure sores and respiratory infections. This reality has been exacerbated during the pandemic. LTCF responders report that those with COVID-19 have seen their nutritional status deteriorate rapidly. At the same time, unaffected residents also exhibited significant and undesirable weight loss. Interventions to prevent weight loss should aim to increase energy and protein intake. The use of oral nutritional supplements is a popular way to achieve this goal. However, the actual consumption of these products is rather low. Since 2017, an intervention dubbed NAM for ""Nutrition as Medication"" has been developed and tested in LTCH by our team. This intervention suggests prescribing small doses of an oral nutritional supplement (30 or 60 ml) which are administered as a medicine. The effectiveness of NAM has been studied. Preliminary results show a high delivery rate (93-95%), a significant improvement in nutritional status and a decrease in pressure ulcers among residents. Following these results, a guide was written describing the NAM intervention, the principles that frame it, and the suggested strategy for successful implementation in an LTCF. The NAM intervention appears to be a promising practice that could limit or even prevent the deterioration of the nutritional status of residents, whether or not they have COVID-19. However, the studies were carried out before the onset of the pandemic and the implementation guide therefore does not take this context into account. Thus, with the aim of better equipping LTCFs during the new wave of COVID-19, our team proposes the dissemination and scaling up of the NAM intervention in LTCFs. Specifically, we propose to: 1) support the implementation of NAM within two Montreal ESLDs; 2) to evaluate the implementation of the NAM in terms of prescription and administration of the treatment; 3) identify facilitating and constraining factors for NAM implementation; 4) identify the effects of NAM as perceived by workers and relatives/residents; and 5) review NAM implementation hardware.]",2020,-99,CIUSSS du Centre-Sud-de-l'Île-de-Montréal,112498.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20295,Unknown,"Optimizing the resilience to COVID-19 of long-term care facilities serving linguistic-cultural minorities in Manitoba, New Brunswick and Quebec: evaluation and co-construction of innovative approaches to optimize the social participation of families and caregivers in the challenges of potential outbreaks","Google translate: In Canada, 81% of deaths from the first wave of COVID-19 occurred in long-term care facilities (LTCFs). To this heavy price is added the threat of a second wave, already started in several jurisdictions. Public health measures that reduce contact with professionals, families and caregivers, wall off LTCFs. This particular context, which includes the restriction of visits, deepens the isolation and loneliness of the elderly (AP), especially in a minority context. These vulnerabilising collateral effects for PAs, not anticipated in the response, are today strongly experienced by ESLDs. This unique and alarming situation compels LTCFs to develop promising practices for the present and future outbreaks and ensure the maintenance of social capital between PAs and their families and caregivers, as well as with staff, to break the isolation. and loneliness. In Quebec, a third of COVID-19 infections have concerned health care personnel. LTCFs, the setting par excellence for seasonal outbreaks (eg flu), are already operating understaffed, exhausted and fearful of infection. The vast majority of LTCHs do not integrate digital technologies optimally to support staff. No one was prepared for the challenge of COVID-19, but the innovations implemented so far indicate islands of success, winning practices that our project will capitalize on, focusing on linguistic-cultural minorities (English-speaking LTCFs from Quebec and francophones from Manitoba and New Brunswick). Indeed, few initiatives concerning COVID-19 are reported among these populations and the situation could be more difficult among IPs in the context of a linguistic-cultural minority who ordinarily encounter challenges in accessing the health system. Given the very limited number of LTCFs dedicated to these minority populations in the provinces, families and relatives are often geographically far away, even in other provinces of the country, digital solutions appear particularly relevant. Of the six strategic options, the project hinges on the presence of families (no. 6), as key partners in caring for and breaking loneliness. Subsidiarily, it involves the 2) preventive and 3) effective aspects. The goal of the project is to identify and implement promising best practices and policies and create a community of practice for the purposes of mitigating the isolation and loneliness of PAs in per and post COVID-19 to ensure safe and quality care in LTCFs.]",2020,-99,Université de Saint-Boniface,112388.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2020 +C20296,Unknown,For our mental health and psychological well-being during a pandemic: Partnership for an online implementation of the Recovery College model,"Google translate: The current pandemic has a clear negative impact on the mental health and well-being of the population, in particular for health workers, on the front lines and vulnerable clients. This project aims to evaluate the online adaptation of the training activities of the Center d'apprentissage Sante et Retablissement, the French-speaking Health and Recovery Learning Center of Canada, in response to the needs of the health sector. These settings want to support the mental health, psychological well-being and resilience of their vulnerable workers and clients (women, people with mental or chronic illness, people with disabilities, caregivers) by allowing quick, free access and online has co-learning trainings. Established initially in England, then in 22 countries, the Health and Recovery Learning Centers put forward a unique educational approach where everyone has access to training on well-being and mental health, the recovery of the power to act and recovery and better living together. The model is based on the sharing of knowledge and the proximity of learners from various backgrounds. By participating in training, learners collectively equip themselves and reflect both on their own way of taking care of themselves as well as on their attitudes, behaviors and practices in terms of mental health. For the past two years, the Health and Recovery Learning Center has been funded and directed by a group of 12 partners from different sectors of activity (health and social services, educational settings, civic organizations, academic settings). Together, they set up the first French-speaking Health and Recovery Learning Center in Canada offering a range of training in different cities of Quebec (santeretablissement.com). To date, no training has been offered online and adapted to the needs of health care settings in the context of a pandemic.]",2020,-99,Université du Québec à Trois-Rivières,148035,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Disabled persons | Women,Caregivers | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20297,Unknown,"What are the repercussions of the COVID-19 pandemic on the mental health of children aged 5-12, and what are the specific issues for children with disabilities or with chronic illnesses? A scoping review of the problems experienced and promising courses of action.","Google translate: COVID-19 has had an impact on everyone's daily lives, including primary school-aged children aged 5 to 12 who can suffer from stress and anxiety. Some children may be at greater risk for mental health problems, including those with disabilities or chronic illnesses. We know that these children may be at higher risk of mental health issues than their peers, and confinement, reduced face-to-face services and changes in routine can have a significant impact on them. This study will synthesize knowledge about the repercussions of the COVID-19 pandemic on all children aged 5 to 12, highlighting the particular impacts on students with a disability or chronic illness. The study will also explore the risk and protective factors for children's mental health, as well as promising avenues of intervention to promote better mental health in these young people. The question that will guide the knowledge synthesis will be the following: What are the repercussions of the pandemic on the mental health of children aged 5-12, and what are the particular issues for children with disabilities or with a chronic illness? Relevant information will be extracted from scientific writings and various reports. The information will be analyzed with a committee of partners including families and health and social services workers. A consultation will be carried out in order to anchor the results of the knowledge synthesis in the Quebec context. The recommendations of the study will support the mental health of all Canadian children aged 5 to 12 and concrete actions in Quebec related to confinement and the return to school. Special attention will be paid to children with a disability or chronic illness in order to promote health equity.]",2020,-99,Université de Sherbrooke,37500,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20298,Unknown,"Best practices for community-led strategies to boost vaccine confidence: A case study in Parc-Extension, Québec","The most racially diverse and socio-economically disadvantaged neighbourhoods in Canada, primarily those concentrated in large urban areas such as Parc Extension in Montreal, Quebec experience have been vaccinated at lower rates despite availability. The lower vaccination rate among residents in Parc Extension is attributable to vaccine hesitancy, characterized by uncertainty and ambivalence about vaccination, a legitimate viewpoint, underscoring the failure or lack of an effective public health system. In response, new and reimagined vaccine interventions that are community-led, culturally-relevant, and place-based have been developed in Parc Extension to successfully increase vaccine confidence and uptake. There is a clear need for better quality studies on the use of community-led vaccination strategies in promoting confidence, particularly in low income and diverse regions in Canada, where research capacities are limited. This proposed community-based research has the fundamental goal of producing qualitative evidence guided by grounded theory using Parc Extension, Quebec as a case study in understanding dynamic community-led responses and developing a best practices implementation toolkit to address vaccine hesitancy. Semi-structured interviews will be conducted with diverse key stakeholders in Parc Extension to understand the best practices required to establish successful and effective community-led vaccine strategies. Data will be analyzed using open-coding and synthesized member-checking to develop a best practices toolkit to implement sustained effective community-led strategies to achieve vaccine confidence among low income and racialized communities in Canada.",2021,-99,McGill University,151932.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20299,Unknown,"Understanding and mitigating the impact of the COVID-19 pandemic on young people, families and school environments in remote regions","Google translate: The COVID-19 pandemic and the resulting measures have important consequences on the health of young people and families, as well as on school environments. Despite these difficulties, the containment measures have generated certain positive impacts for young people and families, such as an increase in quality time spent with family, a reduction in stress related to travel and social commitments, as well as an involvement increase of parents in their children's school activities. The impact of the pandemic on young people and families is therefore varied and depends on several vulnerability factors. In such a context, this qualitative study will make it possible, through 73 interviews, to highlight the discourse of young people, parents and school staff in Saguenay-Lac-Saint-Jean (Quebec) on the consequences of pandemic on their health and their adaptation to it, with regard to social, academic and digital inequalities. It will be conducted in collaboration with two school service centers (CSS) in the region through individual (parents) and group (students and school staff) interviews in elementary and secondary schools. This project offers a promising avenue to better understand the consequences of the pandemic on the health of school actors in remote areas, a subject that has not been studied much to date. It will identify the strategies that seem most effective in dealing with inequalities in schools and the consequences of the pandemic. This data can be integrated into the support services offered by educational establishments with a view to improving the quality and effectiveness of the assistance offered to young people and their families during and after the pandemic.]",2021,-99,Université du Québec à Chicoutimi,64202.51,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20300,Unknown,COVID-19 and Vaccine Trust in Black Communities: State of Play and Education and Engagement Programs,"Google translate: How to explain that the COVID-19 pandemic continues to have more devastating consequences for racialized communities when they are the least disposed to preventive measures such as vaccination? To date, this question has no answers because there is a lack of reliable information to enlighten the authorities and public health policy makers in Canada. Our project aims to better understand the factors that explain the mistrust of Black communities in Canada towards vaccination against COVID-19. More so, it will help to understand how these factors evolve and change over time, depending on the evolution of the pandemic and associated health measures as well as the vaccination promotion campaigns at the heart of this project. Participants in this research will be recruited in Ontario and Quebec, both vaccinated and unvaccinated; these two provinces bring together nearly 80% of black communities in Canada. They will provide information about their profile and whether or not they want to get vaccinated, their knowledge, beliefs and attitudes towards COVID-19 vaccines, experiences of discrimination and their mental health. Focus groups will also be held with vaccinated and unvaccinated participants, Black community leaders, and primary health care and public health professionals. The information collected will be analyzed and the results will make it possible to set up educational campaigns on the vaccine. These campaigns will reduce erroneous or false beliefs about vaccines and increase confidence in the benefits of getting vaccinated against COVID-19. The programs and tools that have proven themselves through this project can be used in the future in other vaccination contexts with Black communities in Canada and elsewhere in the West.]",2021,-99,University of Ottawa,158000,Human Populations,Black,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20301,Unknown,Covid-19 and infodemic: information practices of groups in a situation of vulnerability to COVID -19 in Quebec in the context of a pandemic.,"Google translate: The historic measures put in place to protect the population from COVID-19 have upset the daily lives of the inhabitants of Quebec, just like the inhabitants of the planet. The pandemic has been accompanied by a steady stream of information to such an extent that the WHO uses the term ""infodemic"" to describe information overload. This proliferation of information accentuated by social media can have harmful repercussions for some people. Excess information can generate fear, anxiety, mistrust of health authorities, lead to dangerous practices that can lead to death, or even non-compliance with preventive practices. Informational practices are strongly influenced by the socio-economic level, the level of education, the cultural origin or even the place of residence. Thus, the messages of public health authorities do not reach certain groups in situations of vulnerability to COVID-19, such as seniors (60 years and over), young adults (18-25 years), members of cultural communities and members of Aboriginal communities living in urban areas. This is why it is important to identify the information practices of these different groups. The results will make it possible to guide the communication activities of public health authorities to better adapt to the needs of groups in situations of vulnerability to COVID-19, thus making it possible to reach them more equitably and promote adherence to the recommended measures.]",2020,-99,Institut national de santé publique du Québec,120870,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2021 +C20302,Unknown,COvid-19 Vaccines Booster in Immunocompromised Rheumatic Diseases (COVBIRD),"In the midst of a fourth wave and the circulation of the delta variant, Quebec and Ontario offer a third dose of mRNA COVID-19 vaccine to immunosuppressed patients including people living with systemic autoimmune rheumatic diseases (SARD). However, the safety and the response to a third dose of vaccine in rheumatic disease patients is unknown. Moreover, initial results from an ongoing study demonstrated that SARD patients treated with rituximab, a drug that depletes cells producing antibodies, have a poor response to two doses of an mRNA vaccine. Since this group is also less likely to respond to a third vaccine dose, defining strategies to enhance responses to COVID-19 vaccines in these vulnerable patients is a priority. Hypothesis: A fourth dose of a non-mRNA vaccine, in SARD patients treated with Rituximab who do not respond to a third dose, is safe and enhances the number of patients who develop post-vaccine antibody responses. Primary Aims: To evaluate the safety of a 4th dose of vaccine in SARD patients treated with rituximab and the vaccine induced antibody responses. Secondary Aims: To compare the response following a 4th dose of a non-mRNA vaccine; to evaluate the effect of immunosuppressive treatment on the response post-4th dose; to compare the rates of disease flares post-4th dose of a non-mRNA vaccine; to assess the persistence of humoral responses induced by a 4th dose of a non-mRNA vaccines. Design: This multicenter clinical trial will enroll SARD patients on rituximab who did not respond to a third dose of a COVID-19 vaccine. These patients will be offered a 4th dose of non-mRNA COVID-19 vaccines that will be approved in the coming months by Health Canada. Significance: This study is key to inform public health authorities on the advantage of using specific vaccine types to achieve satisfactory vaccination in the most vulnerable SARD patients.",2021,-99,Université Laval,786296.48,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Clinical trials for disease management | Adverse events associated with immunization,2021 +C20303,Unknown,COVIGRO: Impact of COVID-19 and the vaccine against SARS-CoV-2 on the development of the placenta and the fetus,"Google translate: Scientific data regarding the impact of COVID-19 on pregnancy is limited but suggests an increase in complications such as premature birth and preeclampsia. At the same time, scientific data are limited regarding the effectiveness of the COVID-19 vaccine given during pregnancy and whether gestational age can influence its effectiveness and/or impact on the outcome of the pregnancy. We will compare two cohorts of pregnant women, one recruited before the pandemic (2017-2018) and one recruited during the 2020-2021 pandemic. Using blood samples collected at different times of pregnancy, and using a questionnaire, we will be able to establish if the patient has been infected with COVID-19 and if she has received the vaccine. We will assess the effect of COVID-19 on placental development and fetal development, as well as the rate of complications. We will finally assess whether the vaccine received during pregnancy is as effective as the vaccine received before or after pregnancy.]",2021,-99,Université Laval,211866.94,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2021 +C20304,Unknown,Open Sky School: Effectiveness of an intervention program involving nature to mitigate the impacts of school disruptions linked to Covid-19 on the mental health and healthy lifestyles of children from disadvantaged backgrounds.,"Google translate: How to reduce the consequences of the COVID-19 pandemic on the mental health of disadvantaged children, who have been hardest hit? We offer Open Sky School, an outdoor education intervention involving contact with nature. There is currently a craze for outdoor education in schools and especially since the pandemic. Could such practices have salutogenic effects? Experimental studies conducted all over the world show that contact with nature (urban park or forest) improves mental health. Preliminary results seem to indicate that this is also the case in children who are in contact with nature during outdoor learning situations. However, no experimental studies have tested the effectiveness of outdoor education as a strategy for improving children's mental health. We will conduct a cluster randomized control trial to test the effectiveness of the Ecole à Ciel Ouvert program. It is a nature-based, teacher-implemented mental health promotion intervention. The intervention will be spread over 15 weeks, at the rate of two hours per week. We will recruit 80 schools with 5th year primary school classes from underprivileged neighborhoods, among the schools that are already participating in a larger study conducted by the Observatory for Children's Education and Health (OPES). The intervention will include activities that promote mental health in nature (eg cooperation, compassion/empathy, mindfulness) and educational activities. We will assess the impact of the intervention on children's health. The results could help decision-makers to implement an outdoor education program promoting mental health, based on empirical evidence, and having a high potential for deployment at the population level, and this, at low cost.]",2021,-99,McGill University,118150.82,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20305,Unknown,Evaluation of the effectiveness of probiotics on post-COVID-19 conditions.,"Google translate: The COVID-19 pandemic has affected more than 138 million people and if vaccination brings significant hope, many questions remain (eg impact of virus variants). Studies show that patients could present symptoms up to 6 months after the acute phase (fatigue, anxiety, etc.). The causes of long-lasting COVID (LONG-COV) are poorly understood but may be related to virus persistence or an inadequate immune response. Our group proposes to study the impact of the intestinal microbiota (intestinal flora) on LONG-COV. We know that: 1) people who have a severe form of COVID-19 (elderly, diabetic...) often have an imbalance of the intestinal microbiota, 2) COVID-19 modifies the microbiota (ex: taking antibiotics) and 3) probiotics can improve the balance of the microbiota. We hypothesize that LONG-COV is associated with the consequences of gut microbiota imbalance and that it is possible to reduce the occurrence of LONG-COV using probiotics. As the intestinal microbiota is closely related to the lungs and the brain, the action of probiotics could also reach the other organs affected by LONG-COV. We are proposing a study that compares the intake of probiotics to that of a placebo. We will include 618 men and women aged 18 and over, symptomatic of COVID-19 with a COVID+ test for 10 days or less. Hospitalized patients (population at risk of LONG-COV) can be included if they returned home within 10 days of diagnosis. The signs of LONG-COV will be studied on the 30th and 90th day (internet or telephone). A group of volunteer patients will take samples (saliva and stool) for virus and microbiota analyses. If successful, probiotics could be used very quickly across Canada (few side effects, affordable costs).]",2021,-99,Université de Sherbrooke,787845.67,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase)",2021 +C20306,Unknown,Impact of the pandemic on Francophone families in the Canadian Prairies,"Google translate: Over the past 20 years, more and more literature has shown that Francophones, an official language minority in the Canadian Prairies, face linguistic and cultural barriers in accessing health services and suffer the negative consequences their health. The recent pandemic context has exacerbated the minority situation, particularly at the level of families weakened by an unfavorable economic context, recent immigration, dependent dependents or their remoteness from urban centres. The proposed research therefore aims to document in a more systematic way the needs of Francophone families in the prairies and to seek together ways to fill the gaps in obtaining services in French post-pandemic. Francophone families with children from the 3 Prairie provinces will be invited to participate virtually in a conversation called Cafe du monde to share the difficulties experienced during the pandemic and the emerging needs post-pandemic. The information collected and collated will then make it possible to develop a relevant survey that will be widely distributed among Francophone families and young people in the three Prairie provinces to solicit their perspectives on post-pandemic remedial needs and services. The recommendations will help mobilize the community and the various levels of government.]",2021,-99,University of Saskatchewan,115999.65,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C20307,Unknown,Work-family conflict as a gendered social determinant of parental and child mental health following the COVID-19 pandemic,"Google translate: The COVID-19 pandemic and the health measures to contain it have had significant effects on the mental health of children and their parents. They also highlighted the gender differences that persist in work-life balance, despite years of social progress in the pursuit of equity in this regard. However, the unequal distribution of the difficulties of reconciling work and family can not only intervene in several manifestations of the physical and mental health of workers, but also in the physical and mental health of their children. The impact of work-family balance on the mental health of children in Quebec following the pandemic remains unexplored. Current data also do not make it possible to distinguish the gender stressors that emerge from the articulation of two major spheres of life: work and family. Work-family conflict (WFC) is bidirectional since work can interfere with family and family can interfere with work. Considering that 55% of parents of children aged 0 to 5 in Quebec experienced moderate or high work-family conflict before the COVID-19 pandemic, mitigating this conflict and the resulting inequalities is an important challenge for businesses and the various levels of government in Canada to promote the mental health of parents and their children.]",2021,-99,McGill University,117514.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20308,Unknown,Modulation of immune responses to COVID-19 vaccination by gut microbiota intervention: a randomized controlled trial.,"Google translate: The elderly, who often have more fragile health, have been particularly affected by the COVID-19 pandemic. The results of recent studies show that, while the vaccines have shown very good short-term efficacy, the protection of the elders may be insufficient, 6 months after the 2nd dose. Some countries have started to offer a 3rd dose. We plan to act at the level of the intestinal flora of the elderly (which is often unbalanced) in order to increase the effectiveness of vaccination. Indeed, it has been shown that probiotics (which can rebalance the intestinal flora) significantly increase the production of antibodies after vaccination against the flu virus. Our hypothesis is that taking probiotics one month before and one month after the 3rd dose of COVID vaccine would provide longer-lasting vaccine protection in the elderly. Our study will include 668 seniors, aged 65 to 89, who have not had COVID-19, who have received 2 doses of the same vaccine and who will accept a 3rd dose of vaccine. All participants will take one capsule/day (probiotics or placebo) for 2 months and, in the middle of this period, they will receive a 3rd dose of vaccine. Participants will have to travel 3 times to the Sherbrooke Clinical Research Center (inclusion visit, vaccination and final visit). On five occasions (inclusion, vaccination 1 month, 3 months and 6 months post-vaccination), they will prick their fingertips and express the drop of blood on blotting paper. They will mail this dry blood sample in an envelope for the antibodies to be dosed in Quebec. We expect to reduce by 1/3 the number of seniors poorly protected by the 3rd dose of vaccine 6 months after the injection thanks to probiotics. If successful, this approach could quickly be implemented worldwide because probiotics have few side effects and are affordable.]",2021,-99,Centre de Recherche clinique Etienne-Le Bel/CHUS,789849.9,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Immunity | Supportive care, processes of care and management",2021 +C20309,Unknown,Noochokooyishi Anavaan (The Ways Forward): An equity-focused approach on the impact of the COVID-19 pandemic and perspectives on future pandemic responses among Métis in Alberta,"The COVID-19 pandemic has affected people around the world. Yet, the problems of the COVID-19 pandemic are not equal for all. The pandemic has affected Indigenous peoples and increased their risk for poor health. Colonialism has played an important role on COVID-19 consequences among Indigenous people. In particular, we do not know much about Metis experiences during the covid-19 pandemic. The Metis Nation of Alberta (MNA) in collaboration with academic allies conducted the first study in Canada (Misi Yehewin (""big breath"" in Michif) to evaluate physical, mental health and well-being among ~1,500 Metis Albertans aged 16 years and older at different stages of the COVID-19 pandemic. The proposed study, Noochokooyishi Anavaan (""the ways forward"" in Michif), aims to explore risk and resilience factors associated with Metis health, well-being, and health care use during the pandemic and before and after COVID-19 vaccination. The study will also hold community gatherings to understand the experiences of Metis Albertans during the pandemic and will reach consensus among Metis knowledge holders responsible for decisions related to the MNA's responses to pandemics that are responsive to the lived realities of Metis people in Alberta and supportive of Metis' self-determination. This research will inform the design and adoption of culturally appropriate pandemic response plans that consider Metis health and well-being needs.",2021,-99,University of Alberta,192760,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2021 +C20310,Unknown,Prioritization of intensive care in an extreme pandemic context: 1) modeling/simulation of different strategies for prioritizing access to intensive care and 2) democratic deliberations by stakeholders on the values underlying the models and their health impacts.,"Google translate: In the face of a potential shortage, one of the strategies considered in this COVID-19 pandemic has been the development of triage (or prioritization) protocols for access to intensive care. Quebec and Ontario have each developed an adult prioritization protocol for access to intensive care in an extreme pandemic context which aims to allocate resources to reduce mortality in a fair and equitable manner. Fortunately, none of these protocols has ever been applied. Consequently, we do not have data on the impacts that their application would have had. We don't know what the public thinks about it either. These protocols have not been subject to a formal public consultation process. What do the people targeted by the protocol say? This project aims to carry out: 1) a mathematical modelling/simulation of two prioritization strategies (application of the adult protocol and principle of first come, first served) for comparative purposes; 2) democratic deliberations with members of the public based on the results of the modeling of the two prioritization strategies and the values that underpin them. Simulating different prioritization strategies will generate objective data on their health impacts (number of lives saved). Submitting the content of the protocols to deliberation will allow for informed feedback from the public in order to bring out the most optimal model.]",2021,-99,Université de Montréal,165471.03,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2021 +C20311,Unknown,Structural harms and COVID-19 policy responses in Manitoba: Exploring the experiences of Red River Métis,"Why this research is needed: Systematically marginalized populations, such as First Nations/Metis/Inuit (FN/M/I), have been greatly affected by COVID-19 in Canada. This is why people identifying as FN/M/I were prioritized for COVID-19 vaccines. This policy was adopted Canada-wide, except in Manitoba. In Manitoba, only First Nations Peoples were prioritized for COVID-19 vaccines. Inuit and Metis Citizens were to access COVID-19 vaccines following age-eligibility criteria like all other Manitobans. This policy changed in May 2021 in acknowledgement of the ""impacts of colonization on all Indigenous people in Canada"". Vaccines were handled differently during H1N1, where only Manitoba prioritized people of Indigenous Ancestry (FN/I/M) for H1N1 vaccine in Canada. Manitoba's COVID-19 vaccine policy has had a negative impact on vaccine uptake by the Red River Metis. In this project we aim to study: 1.Ongoing COVID-19 vaccine decision-making processes among Metis Citizens; 2.Harms (e.g. COVID-19 infection rates, health service use for COVID-19, lower vaccine uptake) created by a racist policy that disadvantaged Metis relative to all other Manitobans; 3.The impact on possible COVID-19 cases if Red River Metis had been prioritized for vaccination earlier in the pandemic; and 4.Long-term consequences and possible loss of trust among Metis in provincial health systems. Methods: We will carry out focus group discussions with Red River Metis (obj 1, 2, 4) to examine Metis experiences given the provincial public health COVID response, and use whole-population administrative health and COVID vaccination data, updated monthly, to compare Metis experiences to all other Manitobans (obj 2, 3). Impact: As we enter the fourth wave, we need to document the experiences of Red River Metis relative to all other Manitobans. Only then might we be able to better understand how we can close the gap in Metis vaccine uptake.",2021,-99,University of Manitoba,394889.4,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20312,Unknown,Monitoring Immune Responses to the COVID-19 Vaccine in People Living with HIV-1,"Google translate: People who are immunosuppressed or suffer from chronic inflammatory diseases have an increased risk of complications related to SARS-CoV-2 infection, in addition to having an often reduced vaccine response. People living with HIV (PLHIV) also have chronic inflammation, which makes them more susceptible to complications. We will analyze the immune response of a cohort of 100 PLHIV vaccinated against COVID-19 and followed every six months at the UHRESS of the CHU de Quebec. Information on COVID-19 vaccination and risk factors leading to severe COVID will be collected. Serological and cellular immunity analyzes (innate and acquired) will be carried out at admission and at 6 months. A cohort of 200 vaccinated people working in the retail trade (PTCD) and whose data we already have will be used as a comparison group. We propose to complete this transdisciplinary analysis with the study of the innate immune response in PLHIV by analyzing neutrophil responses. Indeed, the human neutrophil being the most abundant leukocyte in the bloodstream and an important player in the development of the innate and inflammatory immune response, we hypothesize that the measurement of the intensity of the functional responses of the neutrophil could predict good vaccine protection, while being different between the cohorts of PLHIV and PTCD. This study will make it possible to characterize the elements of the innate immune response of PLHIV to the vaccine against COVID-19, in addition to establishing the correlations between the cellular response and various serological markers, with the aim of suggesting or not a third dose of vaccine. or the addition of anti-inflammatory treatment. This project will be carried out by a multidisciplinary team covering clinical and fundamental aspects of virology, as well as functional immune responses including the neutrophil.]",2021,-99,Université Laval,395000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20313,Unknown,The Impact of the COVID-19 pandemic on youth substance use problems and services: Knowledge synthesis with Indigenous Nations and organizations,"The COVID-19 pandemic has had a serious impact on Indigenous Peoples across Canada. One area of concern pertains to the exacerbation of substance use problems and the disruption of substance use services for Indigenous youth. This study seeks to understand the impact of the pandemic on substance use risk and resilience among Indigenous youth, via a knowledge synthesis including (a) a rapid review of academic research and other available materials (such as news articles and reports) and (b) interviews and Talking Circles with Indigenous communities and service providers in eastern Canada. The study conception stems from the Indigenous Working Group (IWG) of the Quebec-Atlantic Node of the Canadian Research Initiative in Substance Misuse. The project is a partnership with two First Nations communities, an Indigenous SU treatment facility, and other partners from Quebec and Atlantic Canada. Qualitative interviews and Talking Circles (via video-conferencing technology, as necessary) with key stakeholders, clinicians, and youth will be conducted in order to understand key needs, challenges, and strengths of Indigenous youth in response to the pandemic. The project will include seeking to understand the pandemic's impact on access to culturally-safe services, including access to Indigenous traditional healing practices. The study will be guided by a Two-Eyed Seeing framework, which seeks to understand both Indigenous and Western biomedical perspectives. All research will be conducted in consultation with an Indigenous research advisory council. Data will be analyzed using principles of thematic content analysis. Knowledge from this study will be disseminated to Indigenous Nations and organizations across Canada, as well as to federal and provincial agencies.",2020,-99,McGill University,79000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2021 +C20314,Unknown,Analysis of the professional trajectories of nurses during the health crisis: For strategies aimed at optimizing the retention of nurses and the quality of care,"Google translate:Context: In Canada as elsewhere, certain groups of individuals have been disproportionately affected by the pandemic. This is the case of nurses, strongly mobilized because of the essential nature of their services. Direct witnesses of the effects of the pandemic, they have come to terms with unprecedented administrative measures aimed at ensuring accessibility to health services and extremely difficult working conditions. Nurses left the healthcare system during the pandemic, while others, with potentially different characteristics, continued their commitment or returned to the profession. However, what characterizes these different professional trajectories is not well known. Objectives: 1) Describe the professional trajectories of nurses during the COVID-19 pandemic and identify the determinants; 2) Explore the coping strategies used by nurses on these trajectories, and those they would like to see implemented. Methods: An explanatory sequential mixed study is proposed. Phase 1: a provincial survey will be conducted with a representative sample of nurses mobilized during the pandemic. This survey will identify and describe the professional trajectories of these nurses and their determinants. Phase 2: a qualitative study of the ""experience mapping"" type will be carried out with a sample with maximum variations of nurses who participated in Phase 1 and contrasting in terms of the trajectories and determinants identified. The mappings, produced by focus groups, will make it possible to explain the results of the survey and to determine adaptation strategies. An integrated knowledge transfer approach supports both phases of the study. Contributions: This project aims to create strategies by and for nurses to address the long-term impacts of COVID-19 on nurses and the public.]",2021,-99,Université de Sherbrooke,277103.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health workforce,2022 +C20315,Unknown,COVID19's Impact on Refugee/Migrant Equity-Deserving Groups in Latin America,"Venezuela has been experiencing a severe socioeconomic and political crisis for several years, now compounded by COVID19. With 7.5 million people in need of humanitarian assistance in Venezuela and another 5.6 million Venezuelans in need in other countries, it is now the world's second-largest external displacement crisis after Syria. COVID19 has exacerbated long-standing socioeconomic inequalities between migrants and local communities. This has created an urgent need for research on how the COVID19 pandemic is impacting refugees and migrants in Latin America as well as differential and disproportionate effects on known equity-deserving groups. We will conduct mixed methods research using an innovative 'SenseMaking' (SM) approach to understand the broader impacts of COVID19 in Latin America with a particular focus on different groups of refugees and migrants, including women/girls, LGBTIQ+ individuals, and persons with disabilities. SM is based on the recognition that storytelling is a natural way to convey complex information and is used by individuals to make sense of their experiences. Using SM, participants audio-record a story in response to an open-ended prompt, thus generating the qualitative data. After the recording, participants then interpret their own experiences by plotting their perspectives. SM quantifies each of the plotted points, providing statistical data backed up by the accompanying explanatory narratives. Multiple-choice questions collect demographic information and help to contextualize the shared story. By collecting many self-interpreted stories, SM leverages the ""wisdom of the crowds,"" and collectively, the participants' interpretation responses create a nuanced picture in the same way pixels come together to produce a clear image. Objectives: We will use SM to holistically examine the social, economic, security, health, and cultural impacts of COVID19 among refugee/migrant equity-deserving groups in Latin America.",2021,-99,Queen's University,384965.35,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C20316,Unknown,Effects of a personalized music intervention on mental health impacts of COVID-19 in older adults,"Google translate: Since the start of the pandemic, 43% of Canadians aged 65 and older have reported increased isolation and loneliness, factors that exacerbate stress, anxiety and depression. As music soothes and improves mood, it proves to be an effective intervention to reduce these impacts. This project seeks to establish a portrait of the impacts of COVID-19 on the mental health of seniors in Canada and the psychological effects of listening to music. Preliminary data from an online survey confirms the deterioration of psychological health and the stress of catching COVID-19 or infecting loved ones. Benefits of music in alleviating loneliness and stress are reported particularly in older adults who have tested positive for anxiety or depression. This suggests that listening to music is an effective tool to mitigate the impacts of the pandemic on the mental health of seniors. This project will also test the effectiveness of a personalized musical intervention on the mental health of isolated seniors who have tested positive for anxiety or depression. Half of them will listen to personalized music (music group) and the other half to audio books (comparison group). These two interventions will take place over two months, four days a week. Before and after the procedure, cortisol, the stress hormone, will be measured in hair samples; then the perception of stress, anxiety and depression will be measured with questionnaires. Lower cortisol and perceived stress, anxiety, and depression were predicted in the music group than in the comparison group. This project will help to better understand the impacts of COVID-19 on the mental health of older adults. It will also evaluate the effectiveness of an accessible and pleasant non-pharmacological musical intervention to reduce the impact of pandemics on the mental health of seniors.]",2021,-99,Université de Montréal,237918.45,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C20317,Unknown,Exploring Evolving Models of Care During the COVID19 Pandemic,"Globally alternative models of care have become essential to increase HHR capacity in both acute and critical care settings amid the COVID19 pandemic crisis. Although deploying alternative models of care (e.g. team based models of care where flexible teams practice differently from their traditional scope) were initially planned as a temporary solution to ensure the safe patient care, this approach may need to be used to manage future crises (e.g. impending nursing shortages). To date, no empirical literature on the impact of alternative models of care during COVID19 were found. Given the ongoing need to develop and adapt models of care to ensure the provision of safe care, addressing this gap is paramount. In this context, an embedded case design using a realist evaluation guided by REAIM and the Consolidated Framework for Implementation Research is proposed to capture models of care employed in acute care hospitals including experiences, contextual factors, measures, and lessons learned during implementation. A purposeful sampling strategy will be used to recruit participants (up to 20 per site) from regional, organizational, team, and health care providers from 4 teaching hospitals and 2 community hospitals. Data will be collected through interviews and document analyses with both deductive and inductive analyses. A comprehensive case study database will be created and undergo cross syntheses, in addition to other methodological rigor strategies. An integrated knowledge translation plan with collaborators and knowledge users will be employed. Our proposed research study aligns with CIHR's research areas of understanding the impact of COVID19 pandemic on workforce safety concerns; healthcare workforce concerns; and burnouts, resilience, and health behaviours. Study findings may inform other hospitals in their efforts to optimize safe and quality HHR and care delivery regionally, across Canada, and beyond amid COVID19 pandemic and pandemic recovery.",2021,-99,Sinai Health System,331192.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2022 +C20318,Unknown,Identifying COVID-related mental health problems and resiliency in youth to inform intervention policy from pre-pandemic levels of maternal environmental adversity and mood: The Maternal Adversity Vulnerability and Neurodevelopment Study,"Research demonstrates that environmental adversity (stressful life events, poor housing, financial problems, domestic violence, substance abuse, single parents) and poor maternal mood are associated with increased levels of mental health problems in both mothers and their children. However, not all mothers and children exposed to these risk factors exhibit poor mental health. Research also suggests that major environmental crises (e.g., COVID or large-scale disasters) differentially impact individuals based on pre-crisis factors such as socio-economic disadvantage, family discord, and mental health status. The objective of the present study is to identify resilient and at-risk families (mothers and/or children), using measures of maternal environmental adversity and mood, so that intervention policies that target appropriate families and/or individuals during times of large-scale crises can be established. This objective will be meet using the Maternal Adversity Vulnerability and Neurodevelopment Study: a genetic and sex informative longitudinal cohort with maternal and child data, including repeated socio-environmental and mental health measures, available from pregnancy to late adolescence. The proposed study will collect new COVID-related maternal and child (e.g., resiliency/flourishing, psychopathology, SES, social support, family functioning, and COVID-specific hardship and distress) data. Statistical analyses will assess whether current mental health functioning can be identified based on pre-pandemic factors, particularly environmental adversity and perinatal mood. In conjunction with our Knowledge Users committee, these findings will be used to develop policy for the rapid identification of families at-risk for mental health problems following a major environmental crisis and the establishment of effective interventions based on type of metal health problem, individual (mother and/or child), and family resources.",2021,-99,Lady Davis Institute for Medical Research,385000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C20319,Unknown,"Gambling, problem gambling and the COVID-19 pandemic: The experience of LGBTQIA2S+ people","Google translate: Games of chance and money (GAG) occupy a major place in the consumption habits of the population, both in Canada and abroad. The COVID-19 pandemic has had major repercussions on the practice of gambling (sliding towards online gaming, increase in the practice of gambling among certain at-risk groups, etc.). However, we know very little about the gambling habits as well as the experience of health care and social services during the pandemic of certain marginalized groups such as people who identify with sexual and gender diversity (i.e. LGBTQIA2S+). This situation is worrying since LGBTQIA2S+ people are more at risk of presenting with problem gambling. This study aims to describe the repercussions of the COVID-19 pandemic on the practice of gambling and problem gambling among LGBTQIA2S+ people, to understand the experience and life of LGBTQIA2S+ people with problem gambling and to identify the interventions deemed effective by the LGBTQIA2S+ people regarding problem gambling during the pandemic. Ultimately, this study will make it possible, based on evidence and the experience of individuals, to formulate courses of action to improve interventions as well as health care and social services for LGTBQIA2S+ people. with problem gambling and to reduce the harmful consequences associated with gambling in the LGBTQIA2S+ population in the event of a pandemic and/or future health emergency.]",2021,-99,Université de Sherbrooke,226931.32,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C20320,Unknown,Qanuinngitsiarutiksait 3: Developing mechanisms to ascertain Inuit data sovereignty in Manitoba,"Inuit have long been underrepresented/invisible in the ""data world"". Despite decades of data being collected, Indigenous peoples continue to experience considerable inequities. This has led Indigenous nations to call for data sovereignty, which can be defined as ""managing information in a way that is consistent with the laws, practices and customs of the nation-state in which it is located"". Our overarching goal is to strengthen MIA's ability to engage and respond to pandemics, by expanding its data sovereignty capacity. This proposal is a first step towards the development of an Inuit-centric, state-of-the-art data sovereignty infrastructure built to support MIA's role as an advocate and service delivery organization serving the needs of Inuit. This project will, 1.Develop Inuit Qaujimajatuqangit-informed governance and management policies to ensure Inuit data sovereignty; 2.Create and implement a respondent driven survey mapping where Manitoba Inuit reside, their circumstances and their needs; 3.Survey Manitoba Inuit to document the impact of COVID-19; and 4.Create a data infrastructure to expand MIA's ability to document, advocate for and improve its COVID-19 and other work, and to support MIA's advocacy with federal, provincial and territorial governments. Our project will result in a sustainable Manitoba-led, MIA-based Inuit infrastructure that can be mobilized quickly to support informed decision-making on emerging issues (pandemics), and document needs for program delivery and advocacy. Our approach aligns with Indigenous self-determination and Inuit' aspiration for data sovereignty. Our work will be grounded in discussions (Integrated Knowledge Translation adapted to reflect Inuit Qaujimajatuqangit) with feedback provided by the Isumataiit Sivuliuqtii (Inuit Elders).",2021,-99,University of Manitoba,192500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Health Systems Research | Research on Capacity Strengthening,Health information systems | Systemic/environmental components of capacity strengthening,2022 +C20321,Unknown,Mental health and accessibility to services in a university setting: is diversity a barrier?,"Google translate: The COVID-19 pandemic has had significant effects on the mental health of Canadians. Preliminary results from a previous study conducted by our team show a significant deterioration in the mental health of university students and employees. This is particularly true for people from the five designated groups (women, visible minorities, people with disabilities, indigenous people, LGBTQIAP2S+) in academia. What explains this particularly deteriorated state of mental health for people in these target groups? Could access or lack of access to services, for reasons related to gender, culture, language, disabilities, income and knowledge of available services, be the cause of this aggravation? This study focuses on the mental health of students and employees of the Universities of Quebec network in the context of a pandemic and aims to gradually achieve 4 general objectives: 1) Identify the repercussions of COVID-19 on the mental health of people who identify with one or more of the five designated groups; 2) List the main mental health services available in a university environment in order to meet the needs of these people; 3) Determine the factors that facilitate or hinder their access to these services; 4) Prioritize the best support services to put in place to support their mental health. In order to achieve these objectives, a research-action taking the form of a living laboratory is proposed. The knowledge resulting from the work will take the form of practical tools that can be used by the partner settings, as well as an action plan to promote the mental health of people who identify with one or other of the five designated groups. in a university environment]",2021,-99,Université du Québec à Chicoutimi,257210.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health service delivery,2022 +C20323,Unknown,The Mental Wellness of Citizens of the Métis Nation: Before and during COVID-19,"The COVID-19 pandemic has been challenging and stressful for communities with ongoing changes, disruptions, and isolation. This has led to high levels of mental unwellness. Rates of anxiety and depression are on the rise across many groups. Yet little information is available on the mental wellness of Indigenous people related to the COVID-19 pandemic. Data that is available suggests continued disparity with poorer mental health in Indigenous compared to non-Indigenous populations. What remains unknown is Metis-specific mental health experiences. High-quality, timely data on the mental health outcomes of Metis people is crucial to inform the allocation of scarce mental health resources. Our rapid COVID-19 study will provide this information. As the only recognized Metis government in Ontario, the Metis Nation of Ontario is well positioned to lead this research to examine the mental wellness of MNO Citizens before, during and after the COVID-19 pandemic. Our study will use mixed methods to examine self-reported mental health through survey based data as well as health service administrative data and speaking directly with Metis Citizens to look at trends in mental wellness. Examining the experiences of mental wellness and unwellness among Metis Citizens during the pandemic is critical to informing the development of programs and strategies to improve outcomes post-pandemic and prepare for future pandemics or other public health emergencies. Results from our COVID-19 study can help inform decisions on resource allocation and prevention/intervention strategies to optimize Metis health.",2021,-99,Métis Nation of Ontario,192500,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +C20349,202012MFE,Leveraging host peroxisome biogenesis and activity to dampen replication of emerging RNA viruses - an approach towards host directed antiviral development.,"Viral outbreaks can impose devastating burdens on our social and economic systems. Since 2015, emerging alphavirus and coronavirus outbreaks have resulted in more than 50 million human infections. While alphaviruses cause encephalitis and arthritis, coronaviruses such as SARS-CoV-2, can cause severe acute respiratory diseases such as COVID-19. Unfortunately, there are no licensed specific antiviral therapeutics or any approved vaccines yet. To address the need for therapeutics against alphaviruses and coronaviruses, I will investigate how these pathogens affect the formation and functions of a host organelle called the peroxisome. Peroxisomes are best known for controlling lipid metabolism and reactive oxygen species and their activity and abundance can be modulated using a variety of clinically tested and licensed drugs. However, recent studies revealed that peroxisomes are important for the interferon pathway, a critical response by our cells that provides natural protection against many types of viruses. Moreover, the Hobman lab showed that increasing peroxisome numbers dramatically inhibits replication multiple viruses, including Zika virus, a flavivirus that was responsible for a large epidemic in 2015. Viruses evade the interferon induction and signaling pathways by hijacking cellular proteins. Because peroxisome biogenesis and activity are controlled by multiple cellular pathways, it is critical to understand how different RNA viruses affect these processes. In doing so, it should be possible to devise therapeutic approaches based on drugs that induce peroxisomes through specific pathways. Using a global approach, I will determine how virus-encoded proteins from alphaviruses (Mayaro virus; Chikungunya virus) and coronaviruses (SARS-CoV-2) interact with cellular pathways that affect peroxisomes. It is expected that this work will lead to the development of broad-spectrum antiviral strategies that activate the interferon system by upregulating peroxisomes.",2020,2023,University of Alberta,101250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +C20350,202011FBD,Temporal transcriptomic and epigenetic analysis of leukocytes in sepsis and COVID-19 patients,"Sepsis is a life-threatening condition caused by the body's severe response to infection. Those who survive sepsis can develop long-term symptoms such as a persistent impairment of the immune system. This weakens the ability of sepsis survivors to fight infections and increases their risk of rehospitalization and death. Post-sepsis care is still poorly researched despite scientists predicting that rehospitalizations due to sepsis are increasing, especially with the COVID-19 pandemic. Sepsis is the most common life-threatening complication of COVID-19 and COVID-19 survivors can have similar long-term symptoms as sepsis survivors. It is not well understood why the immune system remains dysfunctional months after sepsis. To answer this question, we need to track how the immune system of a sepsis patient changes over time. My project will examine changes in gene expression (what genes turn on or off) in patients during and after sepsis, as well as in COVID-19 patients with sepsis, to determine what immune pathways are malfunctioning. At the same time, I will investigate changes in DNA methylation, which is an epigenetic process where methyl group molecules are added to areas of DNA to turn genes off for long periods of time. I hypothesize that DNA methylation is ""locking in"" the changes in gene expression to cause long-term immune dysfunction. I will then test if targeting the genes and pathways identified from these patient studies can prevent immune dysfunction in a cell model. The results from this project will identify the processes that cause long-term immune dysfunction, which is the first step for developing treatments that prevent sepsis survivors from falling sick again. Another potential outcome is the discovery of new biomarkers to diagnose sepsis patients earlier or predict patient survival. Overall, this project will help address a devastating but under-researched consequence of sepsis that affects many sepsis survivors.",2020,2023,University of British Columbia,78750,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +C20351,202012GSM,Functional Somatic Disorders: Understanding the patients experience of patient-physician communication,"Conditions such as Chronic Fatigue Syndrome, Fibromyalgia, Post-Viral Illness and Medically Unexplained Symptoms cause high rates of disability and impact the lives of millions of Canadians. Many doctors find it difficult to explain these conditions to patients and this can lead to misunderstandings and frustrations for patients and doctors. There is little guidance for doctors on how to best explain these conditions because there is relatively little research in the area. Particularly, there is a lack of focus on understanding the patient point of view when studying these communication breakdowns. Better understanding of the patients' experiences will help to identify the best ways for doctors to discuss these conditions with their patients. This project has three parts, each of which will help doctors better understand the patient experience of communicating about these conditions. First, I will create a review article covering the research that has been done so far. Review articles help doctors understand what is known so far and highlights questions not already answered in previous studies, which can then be studied. Second, I will do a survey of patients with post-COVID-19 symptoms, a type of post-viral illness, looking to help doctors understand how these symptoms impact patients' lives. Third, I will do interviews with patients to explore the patients' experience and what influences communication between doctors and patients. These interviews will help provide support for guidelines to help doctors improve the way they discuss these conditions with patients. Altogether, it is expected that the results of this project will help improve communication between doctors and patients with these type of conditions.",2020,2021,University of Calgary,223875,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health workforce",2020 +C20352,202011CGV,Co-Developing & Piloting a New Model of Care Delivery for Migrant People Living with HIV in Montréal,"As of June 2019, immigrants accounted for 82.8% of Canada's annual population growth. Immigrants represent an increasing proportion of people living with HIV (PLWH) in Canada. In fact, a Canadian surveillance report indicated that immigrants accounted for 40% of all new HIV diagnoses reported in 2018. Efficient access to HIV care for new immigrants has significant individual-level health benefits (e.g. reducing the morbidity and mortality associated with HIV infection), which can translate into major society-level benefits (e.g. prevention of HIV transmission to others). However, immigrant PLWH face longstanding and complex barriers that prevent them from accessing and adhering to HIV care compared to native-born citizens. For example, immigrants often lack medical coverage and have limited financial resources to access HIV medications. Furthermore, immigrants are often unable to fluently speak English or French, making medical terminology harder to understand for them and hindering their ability to navigate the Canadian healthcare system. Also, personal barriers such as fear of being stigmatized when accessing HIV care, and organizational barriers such as scheduling appointments at HIV clinics, have both intensified with the COVID-19 pandemic. A possible solution to mitigating or eliminating a number of the barriers immigrants face is to conceive and implement a new model of HIV care specific to this population. This likely means giving healthcare providers a set of specific guidelines to follow when working with this population and integrating clinical care with social programs from community-based organizations that serve immigrants. My research program seeks to do the following: (1) co-design a model of care with patients, clinicians, community organizations, and hospital administrative decision-makers; (2) co-design an efficient implementation strategy with all stakeholders; and (3) test this new model of care at two major HIV care centres in Montréal.",2020,2023,McGill University,112500,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20353,202010CJP,Artificial Intelligence based adaptive and interpretable models for analyzing multi-track epigenomic sequential data,"In this project we will take a fresh approach to harness the great potential of AI in the big data-analyses of epigenomic sequences. Epigenetics is the study of molecules and mechanisms that can perpetuate alternative gene activity states in the context of the same DNA sequence. Key factors in epigenetic control are chemical modifications to DNA and histones, which establish a complex regulatory network that controls genome function. Although epigenetic marks are established early during development and differentiation, adaptations occur throughout life in response to intrinsic (e.g. oncogenes) and environmental stimuli (e.g. diet) and may lead to disease late in life. Moreover, epigenomes react to environmental influence (e.g. maternal care, diet, exposure to toxins) with possibly long-term consequences. Thus, the life of an individual is not only defined by their genome, but also by their epigenome, which is flexible and changeable throughout the lifetime. The research team has two epigeneticists (Yamanaka, Davie) and two artificial intelligence (AI) experts (Ashraf, Khan). Working as a collaborative team, the four research groups will develop new tools to analyze DNA sequence data that will be able to predict 3D organization and functional aspects of these interactions in vertebrate epigenomes, which would be transformative in epigenetics research. We also propose the paradigm of iteratively refining the AI models through wet-experiments. In cancer, resistance to specific treatments often results in worse outcomes. It is now known that the 3D organization of the genome gets modified in these cancers. These sequence changes affect genome interactions and predispose some individuals to disease or an inadequate response to a virus attack as in COVID-19. Our studies have the potential to exploit the genome-wide data to predict the changes in the 3D organization of an individual's genome and gene activity, adding a new dimension to personalized medicine.",2020,2023,University of Manitoba,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C20354,202012GSM,Using the Perfectionism Social Disconnection Model to Predict Disordered Eating Behaviours in an Undergraduate Sample,"Physical distancing regulations implemented to limit the spread of the novel coronavirus during the COVID-19 pandemic have increased feelings of social isolation globally. Unfortunately, this presents another public health concern as social isolation has been linked to depression, anxiety, and eating disorders. Previous research has shown that people with perfectionistic personality types are more likely to experience adverse mental health outcomes in response to social isolation. This is concerning when considering that, similar to social isolation, perfectionism increases individuals' risk of developing depression, anxiety, and eating disorders. The Perfectionism Social Disconnection Model (PSDM; Hewitt et al., 2006) can be used to understand the relationship between perfectionism, social isolation, and adverse mental health outcomes. The PSDM states that perfectionism creates social disconnection, which increases the risk of experiencing mental health concerns. To the best of my knowledge, this model has not yet been applied to the understanding of eating disorders in adults. This is an important population to study as eating disorders have devastating effects both at the individual level and for society. Further, perfectionism has been found to maintain these disorders. The goal of my Master's research will be to apply the PSDM to a sample of undergraduate students to determine if this model can be used to predict disordered eating behaviours. Understanding this relationship has powerful implications for the prevention and treatment of eating disorders in adults. By addressing underlying contributing factors i.e. perfectionism and social disconnection rather than the specific symptoms, we can uncover treatment targets that can be used to prevent multiple disorders.",2020,2021,Simon Fraser University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20355,202012GSM,Perceived Social Support in Perinatal Populations During the COVID-19 Pandemic.,,2020,2021,McMaster University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20356,202005VR5,The reorganization of institutional and community services for people experiencing homelessness and the needs of people experiencing homelessness to deal with the COVID-19 pandemic,,2020,2021,Université de Montréal,154695.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20357,202009SL5,"Optimizing the resilience to COVID-19 of long-term care facilities serving linguistic-cultural minorities in Manitoba, New Brunswick and Quebec: evaluation and co-construction of innovative approaches to optimize the social participation of families and caregivers in the challenges of potential outbreaks",,2020,2021,Direct Payment,112388.25,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health service delivery,2020 +C20358,202012GSM,Impact of COVID-19 on the Mental Health of Children Under 12 Years Old with Disruptive Behaviour Disorders,,2020,2021,Acadia University,13125,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20359,202005CMS,Gender and dependency intervention in the context of a pandemic with people in a precarious social situation,,2020,2020,Université de Sherbrooke,37460.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20360,202012GSM,Impact of novel anti-CD11d neurotrauma therapy on leukocyte function via outside-in signalling,,2020,2021,Western University,13125,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C20361,202010PJ4,"Role of platelets and their mother cell, the megakaryocyte, in COVID-19",,2020,2021,Université Laval,75000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2020 +C20362,202010PJI,Adaptation and Evaluation of Virtual Group-Based Cognitive Behavior Therapy Classes for Mental Wellness in Public Safety Personnel,,2020,2021,University of Manitoba,37500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20363,202012PHT,The Genetics Navigator: A novel digital platform for delivering personalized genetic services,"Genomic sequencing (GS) is a test that scans a person's genetic code to identify changes that may be disease-causing. GS is increasingly being used for patient care as it improves diagnosis and health outcomes. In spite of these benefits, GS is a complex and costly health service. This results in unequal access, increased wait times and inconsistencies in care. The use of eHealth tools to support GS delivery can result in a better patient experience and reduced distress associated with waiting for results and empower patients to receive and act on medical results. Our study will develop a patient centred eHealth platform to deliver GS services and then evaluate its effectiveness compared to usual care. The platform will include a conversational chatbot and innovative strategies for pre-and post-test genetic counselling and result reporting. First, we will identify the key components of this novel platform with end-users and build the chatbot to provide educational, decisional and emotional support to patients. We will then conduct usability testing with a pan-Canadian sample of patients and health care providers to ensure the platform is patient-centred and optimized for a range of contexts. Next, we will conduct a randomized controlled trial, to understand if our eHealth platform is better than usual care. Patients undergoing GS will be randomly assigned to receive either our eHealth platform or usual care that consists of meeting with genetics providers in-person or over the phone. The outcomes include patients' distress, experience, satisfaction, empowerment, knowledge, perceived utility, behaviour change, and cost effectiveness. This study represents a significant advance in personalized health by developing a novel, comprehensive eHealth platform to improve genetic service delivery, accessibility, patient experiences, and patient outcomes. The shift to virtual care during the COVID-19 pandemic underscores the critical importance of this platform",2020,2024,Unity Health Toronto,1500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C20364,202010PJM,The Genetics Navigator: A novel digital tool to advance quality and equity in genomic medicine,"Genome-wide sequencing (GS) is increasingly being used in routine medical care as it improves diagnosis and informs treatment. However, GS is a complex and costly service. This results in unequal access, increased wait times and inconsistencies in care. The use of digital tools to support genetic service delivery can result in a better patient experience and reduced distress associated with waiting for results and empower patients to act on medical results. Our study will develop a patient centred digital platform - The Genetics Navigator - to deliver genetic testing services and then evaluate its feasibility and effectiveness compared to usual care. The platform will include innovative strategies for pre-and post-test genetic counselling and result reporting. First, we will identify the key components of this novel digital platform and then build the educational, decisional and emotional support components. We will then conduct usability testing with a pan-Canadian sample of patients and health care providers to ensure the platform is patient-centred and optimized for a range of clinical settings. Next, we will conduct a pilot randomized controlled trial, to understand if the Genetics Navigator is feasible to use and better than usual care. Patients undergoing genetic testing will be randomly assigned to use either the Genetics Navigator or usual care that consists of meeting with genetics providers in-person. The outcomes related to feasibility include acceptability, satisfaction, and patient engagement and the outcomes related to effectiveness include patients' distress, empowerment, knowledge, and behaviour change. This study represents a significant advance in health service delivery by developing a novel, comprehensive digital platform to improve patient experience, access to less well-served communities, and clinical workflow efficiency. The shift to virtual care during the COVID-19 pandemic underscores the critical importance of this work. ",2020,2021,Unity Health Toronto,75000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C20365,202007MS2,For our mental health and psychological well-being in times of pandemic: Partnership for an online implementation of the Recovery College model,,2020,2021,CIUSSS Est-de-l'Ile-de- Montréal-Maisonneuve Rosemont,148035,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20366,202012GSM,Exploring the relationship of COVID-19 with stigma and mental health among community-based outreach workers in the Philippines,,2020,2021,University of Waterloo,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Western Pacific,Western Pacific,,,,Philippines,Philippines,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20367,202005CMS,"What are the repercussions of the COVID-19 pandemic on the mental health of children aged 5-12, and what are the particular issues for children with disabilities or with a chronic illness? A scoping review of the problems experienced and promising avenues for intervention.",,2020,2020,Université de Sherbrooke,37500,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20368,202012MFE,In vivo imaging of host-SARS-CoV-2 interaction in the lung of mice and the role of alveolar macrophages in the disease pathogenesis.,,2020,2023,University of Calgary,101250,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity",2020 +C20369,202012GSM,Opioid Prescribing Preferences and Risk Mitigation Strategies of Ontario Dentists and Dental Specialists Prior to and During the COVID-19 Pandemic,,2020,2021,University of Toronto,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Dentists and dental staff,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20370,202007MS3,"Psychological well-being of housekeeping staff in Canadian hospitals, determining factors and influencing conditions in times of pandemic (COVID-19).",,2020,2021,University of Ottawa,149271,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20371,202012GSM,Mapping Conspiracy Beliefs and Psychological Distress During the COVID-19 Pandemic in Canada,,2020,2021,Université de Montréal,13125,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication | Indirect health impacts,2020 +C20372,202009SL5,"COVID-19: Implementation of virtual P.I.E.C.E.Sâ""¢ for resident care planning with family to build and sustain team collaboration and resilience for the workforce in LTC",,2020,2021,Western University,112500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health workforce,2020 +C20373,202012MFE,Improving young adults' experiences with and access to digital health interventions in the context of COVID-19 and beyond,,2020,2023,University of British Columbia,101250,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2020 +C20374,202012GSM,Study of the mechanism of action of ozanimod in the context of COVID-19,,2020,2021,Université Laval,13125,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20375,202012GSM,Moral Injury and Canadian Health Care Workers During COVID-19: Experiences in a COVID-19 Unit,,2020,2021,McMaster University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20376,202010PJT,Investigating the unique experiences and needs of youth and young adults who use drugs during the dual crises of overdose and COVID-19,,2020,2025,Simon Fraser University,569276.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Drug users | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C20377,202002OV6,La cohésion sociale est-elle possible en situation de crises multiples? L'influence des politiques publiques entourant le coronavirus (2019-nCoV) et les préjugés envers les citoyens et citoyennes d'origine chinoise [Google transalate: Is social cohesion possible in a situation of multiple crises? The influence of public policies surrounding the coronavirus (2019-nCoV) and prejudice against citizens of Chinese origin],,2020,2022,Université de Montréal,263452.5,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +C20378,202012GSM,Effects of the COVID-19 Pandemic on Canadian Pediatric Emergency Departments,,2020,2021,McGill University,13125,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20379,202012GSM,Prenatal and postnatal maternal depression and child brain development,"The effects of the COVID-19 pandemic have led to increased symptoms of depression in pregnant individuals, with 37% of individuals experiencing elevated symptoms during the pandemic, compared to 12% before the pandemic. Depressive symptoms during pregnancy and after pregnancy can lead to behavioural problems in children and altered brain structure in regions of the brain that control emotions. The relationship between maternal depressive symptoms during different time points in pregnancy/postpartum and growth of the child brain over time remains unclear. The objective of this work is to identify how a pregnant mother's depressive symptoms during and after pregnancy might influence child brain growth in infants and in preschool-aged children. Maternal depressive symptoms were measured during pregnancy and after birth. Structural brain data were collected at multiple time points in preschool-aged children between 2.5 and 8 years of age using magnetic resonance imaging (MRI) before the pandemic. Brain images from infants born to mothers during the pandemic will be obtained at 3 months and 12 months of age. Volume and thickness of brain regions involved in emotional control such as the amygdala and hippocampus will be measured, and connections between these regions and frontal areas of the brain will be quantified and observed. Relationships between maternal depressive symptoms in pregnancy and the postnatal period and child brain structure will then be investigated. Through this work we will identify when in pregnancy screening and interventions may be most effective in order to improve outcomes for children and their mothers. This will be one of the first studies to observe the developing brains of infant children born during the pandemic. ",2020,2021,University of Calgary,13125,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20380,202012GSM,Participatory Arts as Social Determinants of Mental Health in Pandemic-Era University Populations,,2020,2021,"NSCAD University, Nova Scotia College of Art and Design",13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20381,202012GSM,Influence of group and online prenatal education services and the COVID-19 context on various indicators related to breastfeeding,,2020,2021,Université Laval,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20382,202012GSM,A Randomized Controlled Trial of MomsInMind: A Mobile Cognitive Behavioural Therapy Application for Postpartum Depression,,2020,2021,University of British Columbia,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Unspecified,,,,,,,,,Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20383,202012GSM,Digital Health Initiative in Canadian Indigenous Communities,"Indigenous Peoples experience health disparities at a disproportionately high rate. The goal of this research is to understand how health sovereignty might address issues of health inequalities and environmental disparities Indigenous Peoples experience. The specific objectives are to i) determine how health and wellness are defined from an Indigenous perspective; ii) work with communities to collect and analyze community health data, with a particular focus on the current COVID-19 pandemic; and iii) identify solutions with communities to address the issues with health and health care access. The study area for this project will include Indigenous communities from across Canada. Information will be gathered through mixed method questionnaires and shared with community members; also, complementary interviews with keepers of health knowledge and community health directors. Important themes reflected in the questionnaire include general health and wellbeing, access to health services and information, mental health, access to and control over food, access to land, ceremony, and demographics. This research is an opportunity to look at how health sovereignty might close the health gap that exists between Indigenous and non-Indigenous people and will play a crucial role in understanding how Indigenous communities are changing and overcoming barriers. It will also help address knowledge gaps related to community health and wellness and the effectiveness of government policies that are being implemented in communities. The holistic nature of this research will allow for better understanding of mental, physical, social, and cultural health in Indigenous communities in Canada. Health projects grounded in community priorities and work toward sovereignty over health are paramount. ",2020,2021,University of Manitoba,13125,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Other secondary impacts,2020 +C20384,202012GSM,Perceptions of intensive care nurses on their preparedness and coping during the COVID-19 pandemic,,2020,2021,McGill University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20385,202005VR5,Implementation of public health measures for vulnerable populations during the COVID-19 pandemic in French-speaking African countries in conflict: Case study in Mali and Burkina Faso,,2020,2021,Université Laval,83613,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa,,,,Canada,Mali | Burkina Faso,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20386,202012GSM,"Analysis of Antibody Neutralization Efficiency, Seroprevalence and Long Term Immunity in SARS-CoV-2-Positive Individuals Identified in a Surveillance Survey of At-Risk Individuals",,2020,2021,University of Ottawa,13125,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +C20387,202011FBD,Exploring Attitudes and Anticipated Uptake of a COVID-19 Vaccine among Patients with Chronic Illnesses in the Canadian Maritimes,,2020,2023,Dalhousie University,78750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2020 +C20388,202012GSM,Assessing the feasibility of nanopore clinical metagenomics in the context of the Coronavirus disease (COVID-19) pandemic,,2020,2021,University of British Columbia,13125,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C20389,202012ID2,Developing wise practices for a culturally safe rapid public health response to COVID-19 with Pikwàkanagàn First Nation,,2020,2021,University of Ottawa,150000,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20390,202012GSM,Measuring the Impact of the COVID-19 Pandemic on all Persons with Dementia,,2020,2021,McGill University,13125,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20391,202010PJT,Mobilizing the Antiviral Capacities of MAIT Cells to Combat COVID-19: From Fundamental Immunology to Vaccine Optimization and Immunotherapy,,2020,2025,Western University,774562.5,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C20392,202012GSM,"Implications of Coronavirus Disease 2019-related worry and isolation for the mental health of cancer patients: The effect of a 24-week mobile health exercise intervention on depressive symptoms, anxiety, and exercise engagement",,2020,2021,University of British Columbia,1099917,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20393,202009SL7,Preserving the link of LTCF residents with cognitive disorders with their loved ones in the context of a pandemic: evaluation of the implementation and effects of virtual and in-person interventions,,2020,2021,Université Laval,79000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +C20394,202011FBD,Digital Epidemiology Applications for Promoting Resilient Health Systems Response to Pandemics,,2020,2023,University of Toronto,749394,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Health Systems Research,Health service delivery,2020 +C20395,202010PJ2,Screening for Suicide Risk among Older Long-Term Care Residents: Assessing the Prevalence and Correlates of Suicide Ideation in an at-risk Demographic,"Older adults have the highest rates of suicide in Canada and worldwide. Efforts are needed to establish the prevalence of suicide thoughts and behaviour in older adults and promote understanding of risk and resiliency factors, to inform suicide risk detection and intervention with vulnerable individuals. The COVID-19 pandemic highlighted serious healthcare challenges in Long-Term Care (LTC) homes, necessitating decisive action to enhance identification of critical health risks and attend to their amelioration. Although Accreditation requirements mandate routine assessment of suicide risk in LTC residents, scant research exists on suicide and its prevention in LTC, basic questions remain unanswered as to the scope of the problem and associated risk factors, and few validated measures have been developed to identify suicide thoughts and behaviour in older adults in LTC contexts. In the present study, we propose to evaluate the assessment of suicide risk in LTC homes. We specifically propose to conduct initial interviews with LTC administrators and frontline providers regarding perceived challenges and possible remedies for integrating suicide screening in LTC. We will then provide an online training program for LTC staff to sensitively screen for and effectively respond to suicide risk in older residents, employing the Geriatric Suicide Ideation Scale-Screen (GSIS-Screen), a brief version of a Canadian tool designed to assess suicide risk among older adults in residential, clinical, and community settings. We will use the GSIS-Screen, along with additional screening tools, to establish the prevalence of suicide thoughts and behaviour in LTC, to assess the measurement characteristics of these tools, and to test a theoretical model of the onset and worsening of suicide risk in later life. Study findings will be shared through the media and mental health and aging networks to enhance understanding of suicide risk in LTC and inform suicide prevention efforts.",2020,2021,Western University,858177,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20396,202010PJM,What Matters' - A digital solution to support person-centered care for people with dementia in care settings,"Canada's aging population and the increasing prevalence of dementia has a significant and growing impact. The COVID-19 pandemic has increased the risk of older people with dementia living in long-term care homes and hospital settings. Social isolation and loneliness are pressing concerns in senior care. The research purpose is to develop and evaluate a mobile app - WhatMatters to address the urgent need for social isolation. We will involve students in nursing, computer science and health design, patient and family partners, frontline staff, and decision-makers in care settings to co-develop and co-evaluate WhatMatters in long-term care and hospital settings. WhatMatters will be an easy-to-use app that offers a personalized list of resources (music, videos, and photographs) to enable staff to deliver person-centered care. Family members can upload or live stream music, photos, and videos to support care for people with dementia in a care setting. Mixed-methods, including observation, focus groups, and interviews, will be used to evaluate WhatMatters, such as what works well and what strategies are needed to overcome barriers. WhatMatters will support continuity of care when the person with dementia needs to move between care locations such as hospitals and care homes. We expect WhatMatters will have benefits for 1. People with dementia (improvement in the quality of life with a decrease in isolation), 2. Staff (increase in job satisfaction with easy-to-use resources for care practice), and 3. Healthcare system (an improvement of workforce capacity with a more person-centered care culture).",2020,2021,University of British Columbia,1218805.68,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Nurses and Nursing Staff | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20397,202012GSM,Neurophysiological and Respiratory Mechanical Mechanisms of Exertional Dyspnoea,"During outbreaks of respiratory diseases, such as the COVID-19 pandemic, health officials have widely encouraged the use of face masks to prevent the spread of infection. In the current COVID-19 climate, the use of face masks during exercise is being strongly encouraged, which has led some to raise concern over the potentially detrimental effects of face masks on their health. However, a recent compilation of data demonstrated that there are no abnormal physiological effects of face masks during exercise in healthy individuals. Despite this, there is consistent evidence that face masks increase the sensation of breathlessness during exercise, which may lead to decreased face mask compliance. Unfortunately, the quality of research in this area appears to be lacking with no studies having systematically examined the physiological mechanisms of breathlessness while wearing a face mask. Accordingly, this study aims to delve deeper into the relationship between face masks and the known mechanism's of breathlessness during exercise through a detailed evaluation of breathing mechanics, respiratory muscle function, and the subjective perception of breathlessness. Additionally, we aim to identify possible sex-based differences in the physiological responses to mask-wearing. Therefore, we hypothesize that face mask-induced breathlessness will be linked to increases in respiratory muscle load and activation during exercise. This study will provide the most comprehensive exploration into the physiological effects of mask-wearing on breathing mechanics and breathlessness, as well as insight into whether alterations in breathing mechanics contribute to exercise intolerance while wearing a mask.",2020,2021,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20398,202012GSM,Telemedicine in the care of older people in primary care: a systematic mixed studies review,"The COVID-19 pandemic has substantially changed the delivery of primary care health services. Most primary care doctors had to adapt to virtual remote care without training. Telemedicine has the potential to improve the quality of primary health care and increase accessibility to the population, however it presents a challenge to older people (e.g. hearing and visual impairment, cognitive impairment, access to the Internet, telephone and video devices). Our research will therefore focus on describing the effects of telemedicine on the quality of primary care for older people compared to in-person care. Our objectives are to identify the different types of telemedicine, describe the various barriers and facilitators to the use of telemedicine by older people and health professionals, and provide our recommendations. We will conduct a mixed systematic review to describe the experience of older people living in the community when using telemedicine in primary care. Our mixed-method approach will combine qualitative data and research techniques (descriptive), quantitative methods (including effect size calculations) and an explanatory approach to mixed methods. A narrative approach (content synthesis and thematic synthesis) will be applied to describe the types of telemedicine, identify barriers and facilitators and draft recommendations on the use of telemedicine by elderly people and health professionals in primary care. Our review will be particularly needed in this period of pandemic during which telemedicine is widely used.",2020,2021,McGill University,559024.54,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Health Systems Research,Health service delivery,2020 +C20399,202012GSM,‘Living’ systematic review on thoracic imaging for the diagnosis of coronavirus disease 2019 (COVID-19),,2020,2021,University of Ottawa,13825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C20400,202012MFE,Evaluating the implementation and effectiveness of British Columbia's risk mitigation prescribing guidelines as a response to the dual overdose and COVID-19 public health emergencies,,2020,2023,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +C20401,202012GSM,Does level of social engagement mediate the relationship between conflicted shyness and substance use?,"ndividual differences in shyness and sociability have been implicated in the development of substance use problems. Individuals who are high on shyness and sociability (i.e., conflicted shyness) are at an elevated risk for developing substance use difficulties. Researchers speculate that individuals with conflicted shyness likely rely on substances to cope with their anxiety created in social situations, although this has never been directly tested. The COVID-19 pandemic provides the opportunity to examine the mechanism through which conflicted shyness is related to substance use because there have likely been significant changes in individuals' levels of social engagement. The proposed study will use a mediated regression analysis to examine whether changes in levels of social engagement during the COVID-19 pandemic mediate the relation between conflicted shyness and substance use. An independent sample of undergraduate students will be asked to complete an online survey and retrospectively report their level of social engagement and their degree of substance use at two different time points: before the COVID-19 shut down and during the height of wave 1 of the pandemic. The online survey will also measure shyness and sociability to index conflicted shyness. We predict that conflicted shyness would be related to reductions in substance use in the context of decreasing levels of social engagement. The findings of this study will provide important insight into specific risk factors of substance use, which can inform prevention techniques and treatment interventions for substance use problems. Moreover, the results will empirically evaluate a longstanding hypothesis related to the mechanism underlying the relation between conflicted shyness and substance use. ",2020,2021,McMaster University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20402,202011FBD,"The mental health consequences of COVID-19 stress on children and parents: A multinational, longitudinal cohort study",,2020,2023,University of Toronto,79000,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20403,202012GSM,Inhibition of SARS-CoV-2 Polymerase,"The current global pandemic due to SARS-CoV-2 has highlighted the need for antiviral treatments. A good target for these therapies has been the RNA-Dependent RNA Polymerase of the virus. Using the baculovirus expression system, the Gotte lab has been able to express the polymerase complex, allowing us to explore potential inhibitors. Using polyacrylamide gel electrophoresis (PAGE), I will be screening potential inhibitors. I will be determining the concentration required to inhibit 50% of activity and also exploring the specificities of the inhibitors. If there is a compound that shows promise, we will study it in cell culture as well as determine the mechanism of action. I believe that my research will contribute significantly to the fight against coronavirus. ",2020,2021,University of Alberta,788676.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +C20404,202010PJT,Molecular mechanisms of host shutoff by respiratory viruses and their contribution to viral pathogenesis,"Viral respiratory disease burden remains high despite continuous efforts to limit virus infection and spread through vaccination, surveillance, and quarantine measures. Now the world is in the middle of a pandemic caused by a novel respiratory virus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite unprecedented efforts by researchers worldwide to develop vaccines against SARS-CoV-2, there is still uncertainty as to whether and when they will become available. Even if vaccines are deployed, people with underlying health conditions will remain under threat. This is true in the case of another respiratory virus, influenza, to which vaccines were developed decades ago, and which continues to cause seasonal epidemics. In Canada, influenza infections peak each year in the late fall and winter months resulting in over 12,000 hospitalizations and over 3,000 deaths annually. This underscores the need for better treatment options for those who develop severe respiratory disease. The long-term goal of our research program is the development of new antiviral treatments based on detailed understanding of virus-host interactions. Specifically, we are interested in the mechanisms used by respiratory viruses like influenza and SARS-CoV-2 to overcome antiviral immune responses. One such mechanism is host shutoff - the blockade of new protein synthesis in infected cells. Both influenza A viruses and coronaviruses produce dedicated host shutoff factors: polymerase acidic X (PA-X) and non-structural protein 1 (Nsp1), respectively. These viral genes interfere with cells ability to synthesise new proteins, including those that are involved in immune responses. In the proposed research, we will determine how PA-X and Nsp1 work at the molecular level and how their function disrupt immune responses to these respiratory viruses. ",2020,2025,Dalhousie University,82950,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,H1,H1N1,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C20405,202012MFE,Virtual peer-to-peer (VP2P) mentoring for adolescents with congenital heart disease: A needs assessment and pilot randomized controlled trial,"Congenital heart disease (CHD) is the most common birth defect in Canada, affecting about 1 in every 100 children. Adolescents with CHD (AWCHD) must learn to independently manage their disease and plan for the future, including the transition to adult care. Many young adults living with CHD find the transition from pediatric to adult care to be challenging, and research shows that between 21-76% of young adults experiences lapses in cardiology care. Patients who do not receive follow-up care as adults have an increased need for urgent interventions and are at an increased risk of requiring hospital admission. These lapses in care can be caused by a range of factors, but often they are related to the challenges young adults experience when learning how to navigate adult healthcare systems, advocate for themselves, and develop self-management and coping skills. One intervention that has helped young adults develop some of these skills to support the transition is peer mentorship. Peer mentorship has been shown to improve health outcomes and symptoms for adolescents with chronic disease, however no research to date has examined the role of peer support for AWCHD. There is a need now more than ever to develop and test virtual support interventions as the COVID-19 pandemic and associated restrictions have limited opportunities for AWCHD to receive peer support. Therefore, the goal of this study to refine and test a virtual peer mentorship intervention for AWCHD which will provide emotional and social support, encourage AWCHD to develop and engage in self-management and transition skills, and provide education related to CHD. This study will be completed in two phases: Phase 1 - a needs assessment, and Phase 2 - a pilot randomized controlled trial to test the feasibility of delivering this intervention. This research will enable us to tailor this unique peer mentorship program to the CHD population, which will allow further study and clinical implementation.",2020,2023,Hospital for Sick Children (Toronto),13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20406,202012MFE,A comparative analysis of Safer Supply interventions to address the dual public health crises of overdose and COVID-19 in BC and Ontario,,2020,2023,University of Victoria,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20407,202012GSM,Explorations into the mechanism and potential of BOLD-100 as a treatment for COVID-19,,2020,2021,Western University,789281.1,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2020 +C20408,202012GSM,Golgi versus endocytic trafficking in the delivery of major histocompatibility complex II molecules to antigen-loading compartments,"Antigen presentation on MHC II is crucial for generating immune responses against pathogens. Unfortunately, many pathogens-including SARS-CoV-2-can suppress immune responses by impairing this process. While the mechanisms for this immune evasion is known for some pathogens, it remains unclear how SARS-CoV-2 limits antigen presentation. During antigen presentation MHC II is loaded with pathogen-derived peptides inside of a lysosome-derived MHC II-loading compartment (MIIC). However, how MHC II is delivered here is controversial, but occurs either via export to the cell surface followed by reinternalization and trafficking to the MIIC, or direct Golgi-to-MIIC transport. We previously identified Erc1 and Rab6-regulators of Golgi-to-lysosome transport-on MIICs. We also demonstrated that Erc1 accumulates on the MIIC and is required for MHC II delivery, supporting the direct trafficking route. Additionally, several components of this trafficking pathway, including Erc1, have been identified as SARS-CoV-2 interacting proteins, suggesting that antigen presentation is manipulated via the direct route. Thus, we hypothesize that Erc1 mediates the direct Golgi-to-MIIC transport of MHC II, and that SARS-CoV-2 targets Erc1 to block this route. Time-lapse microscopy will be used to determine the definitive MHC transport route, and knockdowns of trafficking regulators will be performed to elucidate their role in MHC II delivery. Host proteins found to interact with SARS-CoV-2 proteins through immunoprecipitation and mass spectrophotometry will also be knocked down to determine whether these interactions are necessary for immune evasion. Understanding the mechanisms by which SARS-CoV-2 inhibits antigen presentation will be essential for developing vaccines and therapeutics for COVID-19. ",2020,2021,Western University,39500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +C20409,202010PJT,A novel web-based mental health intervention integrating peer support and clinical moderation to enhance recovery and prevent relapse in adults diagnosed with psychotic disorders: A pragmatic feasibility study of Horyzons-Canada,"The COVID-19 pandemic is having devastating effects on the mental health and well-being of Canadians, particularly, for those living with chronic mental health conditions such as schizophrenia. Psychological interventions have been proven to be effective to support recovery in this population, however, access to these interventions has historically been limited (e.g., due to factors such as limited availability of trained professionals). The restricting measures due to COVID-19 (e.g., no non-essential health visits and guidelines for physical distancing), have made it even more difficult for these patients to access psychosocial therapies. This, in turn, increases the risk for hospitalizations and suicide, in a group where such risks are already high. To address this issue, our team will implement and evaluate an innovative, online psychological and social therapy intervention called ""HoryzonsCa."" HoryzonsCa consists of web-based resources to build strength and resilience, social connectedness, and access to peer support and mental health professionals. We will recruit 100 English and French-speaking adults diagnosed with schizophrenia and other psychotic disorders from: University of Montreal Hospital Centre and the Douglas Mental Health University Institute. We will study the issues that are important to consider when adapting and implementing HoryzonsCa, and its potential benefits. The results will provide health care professionals, hospital administrators, policymakers, patients, and families with important and timely information on the use of technology to improve access to psychosocial therapies for individuals living with chronic mental health conditions, during and after COVID-19. We will communicate results through our well- established and extensive local, national, and international networks within the field of psychosis; and, through online media to accelerate the impact of this study during an important time in Canadian history. ",2020,2023,Centre hospitalier de l'Université de Montréal (CHUM),39500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20410,202009SL4,Supporting mental health and preventing moral injury among long term care+ workers: A mixed methods tool kit development and implementation study,"Long term care+ (LTC+) is at the center of tragic outcomes of COVID‑19 and LTC+ workers are facing pronounced risk for occupational stress related injuries including moral injury. Moral injury results from guilt and/or shame that accompanies knowing what is needed yet being unable to do what is needed owing to constraints outside one's control (Dean, 2020). For LTC+ workers, moral injury may occur from experiences such as guilt over being required to ""police"" end of life visits where family members are only permitted to touch dying loved ones through gloved hands. Moral injury is being newly and necessarily applied to understand occupational stress of health care workers during COVID‑19 because compared to individually focused concepts such as burnout, moral injury locates the source of problems in the structures and processes in which individuals are immersed. Our research question is: how do we support mental health and help prevent moral injury among LTC+ workers? Our objectives are to: 1-gather stakeholder evidence about worker mental health needs and moral injury risks; 2-collect stakeholder assessments of a selection of mental health support/moral injury prevention tools; 3-create and disseminate a mental health support/moral injury prevention toolkit tailored to LTC+ workers in pandemic conditions; and 4-develop theory and evidence-based implementation strategies for scaling and spreading our toolkit.",2020,2021,University of Calgary,79000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +C20411,202011CGV,Developing Glycan-Based Antiviral Prophylactics to Prevent the Spread of COVID-19 and Other Respiratory Infections,,2020,2023,Queen's University,398871,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +C20412,202012GSM,A comparative analysis of the ethical weight assigned to individual rights and collective good in the context of the COVID-19 response by socialist and democratic nations,"The field of global health and its work is generally conceived of in terms of a human rights framework, rooted in the United Nations 1948 Declaration of Human Rights. Few dispute the human rights framework's strong commitment to individual rights; however, individual rights are sometimes defended at the expense of a collective right to public health. In the current context of the COVID-19 pandemic, many countries are facing challenging decisions with regards to the balance between individual freedom and public health. Countries are each approaching the pandemic differently, responding to the individual rights and collective good calculus in varying ways. I seek to understand the relationship between a political context and the weight given to individual rights and collective good – and how that weighing shapes and is shaped by public health crises. To understand this relationship, I propose to study the response to and outcomes of the COVID-19 pandemic in the socialist (collective-minded) context of Cuba and the democratic liberal (individual-minded) context of Canada. A qualitative content analysis of news sources in Canada and Cuba will be conducted to identify the countries' relative weighing of individual rights and collective good during a public health crisis. The outcomes of this analysis will be used to answer the research question: how do the respective political structures of Cuba and Canada, specifically the ethical weight of individual rights and collective good, affect their responses to COVID-19 and public health outcomes? This work will contribute both to the ongoing conversations on the COVID-19 response, as well as the broader conversations on how the work of global health orientates itself to the balancing of individual and collective good.",2020,2021,McMaster University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Governance | Approaches to public health interventions,2020 +C20413,202004FRC,"Population-estimable frailty using ‘big data’ to predict Covid-19 infection and illness severity, Institute of Clinical Evaluative Sciences",,2020,2022,University of Toronto,7110000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity,2020 +C20414,202012GSM,COVID-19 Immunologic Antiviral therapy with Omalizumab (CIAO trial),"The coronavirus disease (COVID-19) has affected over 35,000,000 people across 216 countries, resulting in the death of at least 1,000,000 individuals and the numbers continue to climb exponentially. Despite these staggering numbers, there is currently no standard treatment for COVID-19. Omalizumab is a humanized anti-IgE antibody approved by Health Canada for the treatment of moderate to severe asthma and chronic spontaneous urticaria (CSU). Omalizumab has an excellent safety profile and has been effectively used in children, pregnant women, and patients with severe lung diseases (e.g. asthma, Chronic Obstructive Pulmonary Disease (COPD) and bronchopulmonary aspergillosis). Preclinical and clinical data indicates that omalizumab decreases the duration of hospitalization and need for mechanical ventilation in virally-induced respiratory exacerbations in patients with the aforementioned comorbidities. Additionally, omalizumab has been shown to attenuate inflammatory and pro-coagulable responses, similar to what is found in the acute respiratory distress syndrome (ARDS), the leading cause of mortality due to COVID-19. Although omalizumab demonstrates anti-viral and anti-inflammatory properties, it has not yet been tested for use against the coronavirus species. We therefore hypothesize that omalizumab may have therapeutic potential to treat COVID-19. To test this hypothesis, we propose to to conduct a Phase II, adaptive, placebo-controlled, randomized clinical trial to evaluate if omalizumab improves survival in hospitalized COVID-19 patients with a history of atopy, CSU or asthma relative to the current of standard care. Confirming the efficacy of omalizumab in COVID-19 may help improve patient outcomes and reduce the burden on the health care system. ",2020,2021,McGill University,39500,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2020 +C20415,202012GSM,Effects of Previous Coronavirus Infections on the Immune Response to SARS-CoV-2 Infection,,2020,2021,University of British Columbia,39500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +C20416,202011FBD,"If you build it, will they stay? Improving user engagement with digital health tools in mental health contexts","One in four Canadians reported experiencing mental health issues, such as depression and anxiety, during the COVID-19 pandemic. The unprecedented demand for mental health services has placed tremendous stress on the current mental health system, and the social distancing restrictions have greatly limited the utility of conventional, in-person mental health services. Digital health tools, such as patient portals and mobile apps, are well-positioned to increase capacity for the mental health system and to reduce the burden of mental health challenges in Canada. However, sustained usage with these tools in the real-world environment remain suboptimal. As such, identifying and implementing strategies to improve user engagement with digital health tools is critical to enabling the national and provincial investments in these technologies. The proposed research aims to address this unmet need by examining user engagement with a patient portal that is implemented at a large academic teaching hospital to identify the mechanisms that enhance or detract user engagement with these tools. Using a sequential, explanatory mixed methods approach, a retrospective analysis will be conducted on the usage data of the patient portal to characterize user engagement patterns on the portal for patients seeking mental health care. Based on the usage patterns identified, patients with high and low usage of the portal, as well as clinicians that use the portal with their patients, will be invited to a semi-structured interview to learn about their experiences and factors that may lead to repeated engagement or disengagement with the solution. These findings will inform the identification of strategies that enhance or detract user engagement with digital health tools, which will be of great relevance to mental health clinicians and health system administrators.",2020,2023,Centre for Addiction and Mental Health (Toronto),26250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20417,202011FBD,Intersectional determinants of im/migrant women's sexual and reproductive health access: Informing interventions during COVID-19 and beyond,,2020,2023,Simon Fraser University,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20418,202012MFE,Redefining Population health research agendas in Canada: A multilevel analysis of the COVID-19-related global health governance architecture,,2020,2022,University of Toronto,483480,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health leadership and governance,2020 +C20419,202003PJT,Manipulating mast cells to modify the interferon and inflammatory responses to viral infection,"Viral infections are a major cause of illness and death. This is especially true of respiratory viruses such as Respiratory Syncytial Virus (RSV) which is a major cause of hospital admissions in young children. The devastating impact of such diseases have been further confirmed by the recent COVID-19 outbreak. In each of these diseases, some people respond effectively to infection with little damage to their airways or development of difficulty in breathing while others can develop problems due to inflammation and tissue damage in the lungs, leading to difficulties breathing due to bronchiolitis or pneumonia. Individuals with asthma are often most vulnerable to becoming seriously ill as a result of such infections. In this project we will be examining how to better control such damaging inflammatory responses by understanding how they are regulated and exploring potential new therapeutic targets. In order to complete this work we will focus on a resident immune cell found in the airways and other sites of infection, known as the mast cell. This cell initiates and controls early immune responses to infection and produces many factors that can enhance inflammation and tissue damage as well as factors that can regulate inflammation and combat viral infection. By learning more about these cells and how to control them, we aim to identify new treatments that will substantially reduce the lung damage and deaths caused by such respiratory infections. ",2020,2025,Dalhousie University,26255.65,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C20420,202010PJM,Understanding and improving the care experiences of people with mental-physical multimorbidity during and beyond the COVID-19 pandemic,,2020,2021,Université Laval,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C20421,202012GSM,"SARS-CoV2 Proteins Alter the Mitochondria-Associated Membrane, a Structure that Controls Neuroinflammation","The 2019 coronavirus disease (COVID-19) is an infectious disease, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infects cells of the airways. Additionally, coronaviruses are known to activate inflammatory signaling pathways and cause dysfunction of the brain (neuroinflammation). To address brain defects within COVID-19 patients, a better understanding of the consequences of SARS-CoV2 would be beneficial. The Simmen Lab has previously identified an intracellular structure known as the mitochondria-associated membrane (MAM) as a key control station of neuroinflammation. This structure controls the energy output of mitochondria, but also promotes inflammation. We hypothesized that COVID-19 could trigger the same effect, because several SARS-CoV2 proteins, including ORF8, are known to colocalize with MAM proteins. Indeed, preliminary results from the lab have indicated that SARS-CoV2-infected human cells show changes to the mitochondrial structures and have hallmarks of cell stress. I therefore hypothesize that a subset of SARS-CoV2 proteins compromise the control of mitochondria through the disruption of MAM proteins. To test this hypothesis, I will express SARS-CoV2 proteins in different human cells systems and observe the structure of MAM. Next, I will monitor cellular energy, stress levels, and inflammatory levels. Using different brain cell types, I will test whether response also occurs in these cells and whether it can be transmitted from one cell type to another, a frequent event during neuroinflammation. ",2020,2021,University of Alberta,13825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +C20422,202012MFE,Probing the conformational dynamics of the frameshift-stimulatory pseudoknot of SARS-CoV-2 at the single-molecule level.,"The virus causing the COVID-19 pandemic, SARS-CoV-2, uses a process called -1 programmed ribosomal frameshifting (-1 PRF) to express proteins essential for viral replication. -1 PRF involves a change in the way the viral genome is read that is triggered by a specific structure in the viral genome: a pseudoknot. Changing the level of -1 PRF in viruses can suppress infectivity, suggesting that the SARS-CoV-2 pseudoknot may be a good target for developing new drugs against the coronavirus. It is therefore essential to understand what features of the pseudoknot are important for its ability to stimulate -1 PRF. Work on other viruses has shown that specific interactions within pseudoknots play a key role, as do the dynamics of the structure under tension during -1 PRF. I will build on my previous published work on -1 PRF in SARS-CoV-2 showing that it can be inhibited by small-molecule drugs, aiming to study systematically the mechanisms by which the pseudoknot stimulates -1 PRF. Making mutations that knock out specific interactions within the pseudoknot, one, by one, I will measure both the functional effects these mutations have on -1 PRF, using enzymatic assays, and also the changes they cause in the structural dynamics of the pseudoknot under tension, using high-precision optical tweezers to apply force to single molecules. These studies will allow me to relate specific changes in the structure and dynamics of the RNA to their functional outcomes, and thereby map out the features of the pseudoknot that are essential to -1 PRF. I will also repeat these measurements in the presence of small molecules that inhibit -1 PRF, to deduce the modes of action by which different inhibitors act to change the -1 PRF level and determine which are most effective functionally. This work will provide crucial insights that can be used to target RNA pseudoknots for developing drugs against COVID-19 and possibly other viral diseases involving -1 PRF. ",2020,2023,University of Alberta,471393,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +C20423,202012MFE,Understanding the balance between stimulatory and suppressive functions of neutrophils during SARS-CoV-2 infection,"The new coronavirus that emerged in 2019, SARS-CoV-2, causes respiratory disease, termed COVID-19, leading to a global pandemic. With millions of people affected worldwide and thousands dead, the infection rates continue to rise everyday. Development of vaccines and/or therapeutic drugs is critical to contain and eventually stop this devastating pandemic. Therefore, better understanding of various aspects of the virus and the immune responses it elicits is crucial. Neutrophils are the most abundant white blood cells and are the first line of defence against infections. These cells have proven to be vital for fighting infections when stimulated to certain levels but when over-stimulated, they can also have harmful effects. Indeed, very high neutrophil levels have been recorded in COVID-19. Thus, it is important to understand the in-depth mechanisms controlling the different functions of neutrophils to achieve a delicate balance needed for effective protection. In this study, we aim to analyze the functional changes in neutrophils collected from healthy donors and donors experiencing mild or severe COVID-19. This will shed light on the roles of neutrophils during SARS-CoV-2 infection and help identify potential therapeutic targets. Gaining knowledge about every aspect of this new coronavirus disease is the most effective way to develop new strategies to combat it worldwide. ",2020,2023,Direct Payment,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +C20424,202011FBD,Identifying areas for quality improvement of pediatric emergency and critical care in Pakistan,"Over 6 million children and adolescents die each year, largely in low- and middle-income countries, due to preventable causes. Pakistan is a middle-income country with among the highest number of child and adolescent deaths worldwide. Community prevention strategies, such as sanitation and vaccination campaigns, have dramatically improved child health and survival in Pakistan. However, children continue to develop severe illness due to infectious diseases, injuries and chronic conditions. High-quality emergency hospital services are needed to improve survival for children with these conditions. Challenges to providing essential care include poorly functioning triage systems, insufficient trained personnel, and lack of functional medical equipment and medications. In 2020, the COVID-19 pandemic may place additional strain on the health status of children in Pakistan due to threats to food security, increased poverty, lack of access to primary healthcare and fear of contracting the virus by visiting the hospital. Hospital resources may be overwhelmed by the number of sick adults, detracting from routine and emergency care for children. This project aims to describe causes and rates of death among children and adolescents (0 to 14 years) presenting to district healthcare services prior to and following the onset of the COVID-19 pandemic in March 2020. We will use patient registry data and routine community follow-up to identify risk factors for child death that may be mitigated by improved quality of hospital care. This research will inform subsequent hospital-based care improvement initiatives in Pakistan that are contextualized to the current conditions of the COVID-19 pandemic. ",2020,2023,University of Toronto,79000,Human Populations,Asian,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20425,202012GSM,Social Isolation and Depression Among Older Adults during the COVID-19 Pandemic and Beyond,,2020,2021,University of Ottawa,0,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20426,202010PJT,Pathogenesis of COVID-19 mediated Cardiovascular Complications: Therapeutic Applications,,2020,2025,University of Alberta,1880430.68,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20427,202011CGV,When HIV and COVID-19 Pandemics Collide in Black Communities in Canada,"Pandemics expose inequities in health outcomes,both SARS (COVID-19) and HIV disproportionately impact Black people.The combined impacts of racism, sexism, homophobia, and poverty create acute conditions of exposure that are exacerbated by infectious diseases.Whereas most Canadians are reeling from the impact of COVID-19,Black people also remain in an HIV pandemic zone and must deal with the impact of both pandemics simultaneously.This structural inequities creates conditions of vulnerability that are increased by barriers to effective and timely health care, and increases the Black communities' risks to future pandemics.My research will examine the cumulative impacts of existing and emerging social and public health policies on Black people's health and wellbeing in Canada, focusing on their vulnerability to HIV and COVID-19. It will do so by: (1) tracking the rapidly changing health and public policy landscape in Canada (2) using critical feminist and race theories to analyze,compare and contrast COVID-19 and HIV containment and mitigation strategies; and (3) examining how these policies address, reify, challenge, and uphold existing health inequities from the perspective of Black people living with and at risk of Pandemics in Canada.Using institutional ethnography as my main qualitative method of inquiry,I will analyze the quotidian experiences of Black Canadians and examine the organization of social and institutional systems and policies during pandemics. My personal experiences as a Black woman living with HIV and deep roots in the HIV and Black communities are especially critical for successfully implementation of this ambitious plan.An integrated knowledge translation and exchange plan using multiple forms of dissemination (e.g., scientific papers, policy papers, community forums, and social media) and collaboration with Black organizations, community members, researchers, activists, and scholars will ensure that findings are accessible to diverse audiences. ",2020,2023,York University,78805.66,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20428,202012MFE,Overdose and recidivism among people with criminal justice system involvement and substance use disorders: Identifying longitudinal trends during dual public health emergencies in British Columbia,"People with criminal justice system involvement (e.g. incarceration, criminal charge or conviction) are more likely to use illicit substances (e.g. heroin, methamphetamine) compared to the general population. Those who do, are at higher risk of negative outcomes including overdose and more rapid and/or frequent return to custody. Efforts to address overdose, both in prisons and in the community, have been focused on treatment for people with opioid use disorder, by prescribing opioid agonist treatment. This alone may not be sufficient to reduce illicit opioid use, particularly among people who also use other substances. In March 2020, in the context of COVID-19, British Columbia's Ministry of Health took a significant step to expand access to prescription alternatives to the toxic drug supply and provided doctors with new guidelines and permissions for prescribing opioids, stimulants, benzodiazepines, and alcohol withdrawal management medications to people at risk of overdose. The goal of this study is to evaluate whether these guidelines, which account for coexisting substance use disorder diagnoses, are effective at reducing overdose and criminal justice system involvement. Provincial health and criminal justice records will be examined to identify how many people with and without criminal justice system involvement have substance use disorder diagnoses (and which type of diagnosis) in British Columbia. Trends of overdose and criminal justice system involvement will then be examined, to identify whether there were any changes after opioid agonist treatment expansion efforts, or after the new treatment guidelines introduced in March 2020. Findings will highlight gaps in substance use services in British Columbia, and will inform policies and services intended to reduce overdose in both criminal justice and community health systems.",2020,2023,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Prisoners,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Other secondary impacts,2020 +C20429,202012GSM,Infant and young child feeding in rural Nepal during the COVID-19 pandemic,,2020,2021,University of British Columbia,525785.29,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20430,202006FSS,Telerehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL),"Leg weakness is very common after stroke. It affects the ability to walk and balance among people who have had a stroke. The first year after stroke is an important time for rehabilitation because it is the best time for recovery. Unfortunately, many people who have had a stroke often feel that they do not receive enough rehabilitation to restore their ability to use their legs. This is especially true for people who live in smaller communities where there are few health services, and more recently due to the COVID-19 pandemic where physical distancing between patients and clinicians has limited the amount of in-person rehabilitation. It is therefore important to develop innovative leg rehabilitation programs that are both cost-effective and accessible. Our team of stroke survivors, clinicians and research scientists from across Canada has recently developed TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL). TRAIL is a 4-week program that focuses on exercise to improve leg function. It is delivered using the Internet and computer/tablet by a physical therapist. In this study, we will examine if TRAIL improves walking, balance, leg strength, and quality of life to a greater extent than a 4-week lifestyle coaching program (LIFESTYLE), that focuses on improving physical activity, diet, and stress management. Ninety-two volunteers who have had a stroke in the past year will be randomly assigned to participate in either TRAIL or LIFESTYLE. Volunteers will be asked to complete assessments and questionnaires before and after the programs. Assessments will be conducted using videoconferencing so that volunteers will not need to travel to a hospital to participate in the study. We are working with 5 cities across Canada (Halifax, Toronto, London, Winnipeg, Vancouver). We anticipate that TRAIL is an accessible program that will help improve leg function within the important early window of recovery after stroke. ",2020,2020,University of British Columbia,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20431,202007SKF,Mental health effects of COVID-19 onCanadian adolescents over time: amixed methods study,,2020,2023,Brock University,217250,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20432,202012GSM,Untethering audiology from the clinic: Evaluation of a new technology as a publicly accessible hearing screening tool,"Millions of people across the world live with preventable and treatable hearing loss. It has been estimated that 1 in 3 people over 65 struggle with disabling hearing loss causing decreased quality of life, emotional, social, and communication dysfunction, and in increased risk of isolation and depression. A diagnostic audiometric assessment is considered the most effective means to diagnose hearing loss. However, conventional audiometry is not always readily accessible due to cost constraints, availability of trained audiological professionals, and social stigmatization. It is thus estimated that only 17% of adults who require hearing aids have pursued hearing loss treatment. It has become clear, particularly in light of the COVID-19 pandemic, that efficient, affordable, and accessible hearing screening tools are needed for use outside of clinical audiology settings. The goal of this project is to create a publicly accessible hearing screening test for little or no cost, allowing for ease of access to valid hearing health screening for remote self-assessment and in a wide range of healthcare and community settings. This study will modify the Digit Triplets Test (DTT) to improve sensitivity to specific types of hearing loss using a novel auditory modelling framework. We will use this model to predict audiometric assessment data based on results of the DTT and to determine how best to modify speech sounds to improve predictions. This test would enable non-clinical identification of communication barriers and suggest appropriate referrals in order to prevent further hearing loss and promote hearing health care. A widely accessible hearing screening tool would be an important step in improving the hearing health and related quality of life for millions of Canadians. ",2020,2021,Dalhousie University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20433,202011FBD,Intranasal Delivery of a S. mansoni Cathepsin B expressing Adenovirus Provides Sterilizing Immunity from Schistosomiasis,"Schistosomiasis (schisto) is one of the most important helminthic parasitic diseases in the world. Over 700 million people are at risk of infection. Schisto is acquired by fresh-water parasites and causes debilitating illnesses that can last over 30 years leading to death. Praziquantel is an effective treatment, however drug resistance is emerging, and it does not protect from reinfection. To solve this problem, the formulation of an effective vaccine is pertinent. In recent clinical trials human adenovirus 5 (hAdV-5) has been used as an effective vector to deliver various vaccines for malaria and SARS-CoV-2. It is the hope of this project to develop a vaccine using the same hAdV-5 technology which has moved to clinical trials in previous years. When tested, this vaccine provided 90% protection from parasite infection. We plan to increase this protection by delivering our vaccine intranasally to stimulate immune responses in the lung where the parasite is most vulnerable and prevent infection 100%. The study will be run in both male and female animals to determine sex differences caused by our vaccine. It will also determine the vaccine's ability to harness the immune response by assessing antibody production, and response by immune cells in the blood and lungs. The reality of a schistosomiasis vaccine would not only prove useful to stop transmission of the parasite within tropical and sub-tropical regions (where it is commonly found), but also to travelling Canadians. Additionally, with increased immigration a vaccine which provides sterilizing immunity would reduce the burden of schistosomiasis on the Canadian public health system.",2021,2023,Research Institute of the McGill University Health Centre,985090.5,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Vaccine trial design and infrastructure | Characterisation of vaccine-induced immunity,2020 +C20434,202002OV7,Determination by simulation of the typical profile and values ​​of health professionals who will decide to become involved in the care of patients with COVID-19 or to withdraw from it.,,2020,2021,Université Laval,79000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health workforce,2020 +C20435,202010P13,Identifying and mitigating bias in machine learning models used in population health,"Machine learning (ML) is a form of artificial intelligence that has increasingly been used over the last decade in a variety of sectors, as computing power and the availability of data has increased exponentially. ML applies algorithms to vast amounts of data, and through doing so, are programmed to learn over time in an autonomous fashion. ML has begun to be applied to population-level data, both in health services and in public health. However, it is now well recognized that ML models can replicate biases related to numerous factors including that the data used to train models contains biases, the people developing the models bring their biases to their work, and ideas about causation are biased. As ML is applied in population health, including the COVID-19 pandemic, guidelines to identify and mitigate biases are needed. This project consists of two parts that will occur in tandem. Part 1: We will conduct a scoping review of the literature to identify ML models used in specific areas of population health and to examine whether and how biases were identified. Part 2: We will develop guidelines for model developers to identify and reduce bias in ML models used in population health. Our approach will be informed by standards from the Grading of Recommendations Assessment, Development and Evaluation (GRADE), the UK National Institute for Health and Care Excellence (NICE), and guidelines for statistical model development. We will engage a broad set of stakeholders in the guideline development process. Our diverse team includes national and international experts in computer sciences, statistical modeling, epidemiology, ethics, sociology, public health, and the social determinants of health. This project builds on previous work on public perspectives of AI, ML applied to predicting population health outcomes, and the ethics of AI. Our findings will support efforts to ensure AI applications contribute to reducing, rather than exacerbating, health inequities. ",2020,2021,Unity Health Toronto,13825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues in Research | Social impacts,2020 +C20437,202005VR4,Real-time evaluation of the deployment of connected technologies and the partnership of care and services in the context of the health crisis linked to COVID-19 - the Techno-COVID-Partnership program,,2020,2021,Centre hospitalier de l'Université de Montréal (CHUM),308000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2020 +C20438,202012GSM,Psychological Responses to COVID-19 Among Individuals Living with Chronic Pain: A Web-Based Population Representative Survey,,2020,2021,University of Regina,382256.49,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20439,202012GSM,Blunted Neural Response to Reward as an Index of Stress Susceptibility and Depression in Women,"Major depressive disorder is one of the most common and costly diseases worldwide. Stress is a well-established risk factor for depression, but not all individuals who experience stress will develop depression. Understanding this relationship is now more critical than ever given that the world is experiencing a potent stressor-the COVID-19 pandemic-that is associated with rising levels of depressive symptoms, especially for women. One central need is to identify which individuals are at greatest risk for depression in the face of stress and to understand why. A blunted neural response to reward can be observed not only in people experiencing depression, but also in those at risk for the disorder suggesting that it may be a vulnerability marker for the illness. I believe stress may be key to explaining how these neural responses result in depression. In recent years, my lab has published many studies demonstrating that blunted neural responses to reward render individuals more vulnerable to the effects of stress. Specifically, the reward positivity (RewP), a fronto-central event-related potential (ERP) component that is sensitive to rewards and has been consistently linked to increased depressive symptoms and risk for depression. My proposed research will examine how baseline neural responses to reward predict who will be most likely to experience increases in depressive symptoms following pandemic-related stress. To test this question, I will leverage data from a sample of 109 pairs of women and their adolescent daughters who are vulnerable to depression. This study will be the first to examine reward-related ERPs as a moderator of the relationship between life stress and depression in women in the context of an acute stressor- the global COVID-19 pandemic. ",2020,2021,McGill University,215985,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20440,202011CB2,GREENHOUSE: buildinG ResiliEncE iN youtH thrOUgh cannabiS lEarning,"Cannabis use and mental wellness are important issues in the lives of most young people, particularly in the context of the COVID-19 pandemic and fentanyl overdose crisis. Despite this, young people are rarely supported to draw on their lived experience to lead and participate in research and education related to cannabis use and its impacts on mental wellbeing in a way that responds directly to their concerns, priorities, and perspectives. This is particularly so for young people who are members of marginalized and equity-seeking groups, including those who identify as LGBTQ2S+, racialized and Indigenous youth, immigrant and refugee youth, youth in foster care, and youth living in poverty. With GREENHOUSE, we will generate youth-led evidence for action regarding youth mental wellness in relation to cannabis use. We will accomplish this with activities that are grounded in and responsive to young people's lived experiences. First, we will assess the current state of research on youth cannabis use and mental health in collaboration with youth. Following the evidence review, researchers, decision-makers, and youth will be engaged in discussions on the ways in which the current evidence resonates (or does not) with their experiences. From there, youth will be supported to undertake self-directed learning journeys on cannabis and mental health. Next, youth will apply their learnings from the two previous activities to the creation of youth-led theatre performances and community dialogues centred on youth mental health and cannabis use that will take place in schools and the community. Our Indigenous health partners will ensure that the project proceeds with concrete demonstrations of cultural safety and humility. We believe that this youth-led approach to research and education on cannabis use and mental health can be done in a similar manner across Canada, building a foundation for integrating youth voices in the topics that are important and relevant to their lives. ",2020,2021,University of British Columbia,1925,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20441,202010PJT,High-Flow Nasal Oxygen with or without Helmet Non-invasive Ventilation for Oxygenation Support in Acute Respiratory Failure (HONOUR) Pilot RCT,"Patients with severe respiratory failure (including due to COVID-19) are at high risk of dying and will often require invasive mechanical ventilation. These patients typically require supplemental oxygen. However, the best way to deliver supplemental oxygen to these patients - in order to reduce their risk of dying or requiring invasive ventilation - is not known. This pilot study will determine if it is feasible to conduct a large definitive randomized controlled trial that directly compares two different approaches to delivering supplemental oxygen, each of which has potential benefits and risks: providing oxygen at very high flow rates using nasal cannulas, or supplementing this approach by also providing oxygen using a specially designed helmet interface connected to a ventilator. The results of this work will directly inform the design of the large trial comparing these two approaches, which in turn should identify the strategy that saves more lives of patients with acute respiratory failure, including those with COVID-19.",2020,2022,"Sunnybrook Research Institute (Toronto, Ontario)",77000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2020 +C20442,202012GSM,Ontario Health Teams' Experience with Health System Integration and Resilience in the Context of COVID-19,,2020,2021,University of Toronto,485967.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C20443,202012MFE,A Volunteer Based Telehealth Intervention Program for Older Adults (TIP-OA) with Mental Health/Cognitive Issues: A Randomized Control Trial,"Mental health problems affect 10-15% of older adults, >1,000,000 Canadians, costing >$15 billion every year, which has worsened during and after COVID-19. Current solutions (e.g. psychiatric medications and psychotherapy) are often ineffective, have substantial side effects, require highly skilled personnel, often need to be given in-person, and digital literacy remains a barrier for older adults using telehealth. For this reason, we propose a scalable volunteer based telehealth program, Telehealth Intervention Program for Older Adults (TIP-OA), where trained volunteers provide friendly weekly phone calls to older adults. Currently, we have already served 300 older adults and aim to serve an additional 750-1000 isolated and vulnerable older adults every year. We will conduct a clinical trial randomizing 200 participants to TIP-OA vs. treatment-as-usual (TAU). We will evaluate whether TIP-OA improves stress, fear of COVID-19, depression, and anxiety over 8 weeks. Focus groups and interviews will also be conducted. If successful, this program could empower similar telehealth initiatives in Canada and internationally, and eventually pave the way for digital forms of telehealth in older adults. Through this program immediate, proactive, support could improve the mental health of older adults, save tax dollars from hospital visits, and save lives ",2020,2023,Direct Payment,308000,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20444,202012GSM,Service Engagement in Early Psychosis Intervention Following the Transition to Virtual Care,"Repercussions of the COVID-19 pandemic are expected to be particularly detrimental for youth with serious mental illness, especially persons with psychosis. Access to services is critical for this population, as early identification and treatment in the form of specialized early psychosis intervention (EPI) can significantly improve illness trajectories. The pandemic has disrupted service delivery, urging EPI programs to rapidly adopt models of virtual care; however, little is known of the quality or effectiveness of psychosis services delivered virtually. Historically, one-third of early psychosis patients dropout from services prematurely, though the effect of a transition to virtual care on disengagement is unknown. The present study aims to investigate factors associated with disengagement from a virtual model of EPI as compared to traditional, in-person services. To meet this objective, this project will leverage data collected on an evaluation of the implementation effectiveness of e-NAVIGATE, a structured, virtually-delivered EPI program at the Centre for Addiction and Mental Health, funded by CIHR, the Ontario Ministry of Health, and the University of Toronto. Routinely collected demographic, clinical and service use information will be extracted from electronic health records. Using prior data on in-person EPI, time to disengagement will be compared between the virtual and in-person models, examining factors that predict traditional service disengagement (namely, substance use and lack of family involvement), as well as additional health equity factors thought to impact the uptake of virtual care. Findings from this study may help to inform further development of virtual models, facilitating ongoing delivery of high-quality EPI during the pandemic and beyond.",2020,2021,University of Toronto,459459,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20445,202012MFE,"Patient, primary care provider, and health system factors associated with the use of centralized referral mechanisms implemented to improve patient access to specialized mental health services in Quebec","Accessing specialized mental health (MH) services via primary care is an important public health priority, especially in the pandemic context where psychological distress has increased amid the backdrop of already difficult access to MH services. The Quebec government implemented centralized referral mechanisms (Centres de répartition des demandes de services (CRDS)) to support family physicians (FPs) in referring patients to specialized MH services via primary care. CRDS are single regional access points for processing requests to specialized health services, yet to be evaluated. Psychiatry was one of the last specialties included in the CRDS (2019). Given that it was implemented in the backdrop of already used MH referral mechanisms by FPs (e.g., Guichet d'accès en santé mentale), we hypothesize that FPs' choice of referral system is related to individual and health system factors, as well as patient socio-demographic and clinical characteristics. With this project, we will: 1) better understand the functioning and implementation of the CRDS for psychiatry and its complementarity with existing referral mechanisms; 2) explore how FPs refer patients to specialized MH care and factors influencing their choice in referral mechanisms; 3) assess patient factors associated with target delay achievement when referred to specialized MH services; and 4) explore patient perceptions of their trajectories to specialized MH care and factors influencing these perceptions. This mixed methods project will rely on qualitative interviews with regional decision-makers, FPs, and patients from four Quebec regions: Montérégie-Est, Laval, Chaudière-Appalaches, and Montréal, as well as data on referral indicators from the study regions. Findings will be useful in Quebec, Canada (which has yet to implement such centralized and regional MH referral mechanisms), as well as other countries aiming to decrease consultation times to specialized MH services during and after the COVID-19 pandemic. ",2020,2023,Université de Sherbrooke,306306,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20446,202010PJK,"Supporting Canadians making emergent health decisions to focus on what matters most to them: establishing, testing, and scaling patient-oriented interventions","Since the COVID-19 pandemic, Canadians are facing newly arising tough health decisions. Research shows that when people are supported in making decisions, they have better outcomes. In the last decade, our research team has surveyed patients to tell us about their decision-making needs and created and tested decision support tools as ways to help people make decisions that reflect what matters to them. Yet, little is known about newly arising decisions since the pandemic. We used a rapid process to create 2 decision aids in 2 weeks for people thinking about removing a loved one from a nursing or retirement home during the pandemic (downloaded >10,000 in 3 weeks in April 2020). Yet there is a wide gap in knowing which decision support tools need to be created quickly to meet Canadian's pressing needs in making informed decisions that match what matters to them. We propose to identify emergent decisions Canadians are facing and create a series of field-tested decision support tools to address their decision-making needs. We plan to conduct three surveys of Canadians every 6 months to identify emergent decisions they are facing. We will find, adapt, create, and test decision support tools based on their decisional needs. We will use rapid reviews to follow changing evidence and use a secured collaborative writing platform to allow for new evidence to be added into decision support tools in real time. Then study their use by providing them online and linking them into the electronic medical record. We will provide results for best strategies and create evidence-based decision support tools for empowering Canadians and supporting the important work of clinicians within health systems. Our study also fits Canadians' priorities for making informed decisions that match what matters most to them so their values prevail.",2020,2021,University of Ottawa,38500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C20447,202012MFE,Using data from electronic medical records to understand the impact of COVID-19 on chronic disease management and prevention in primary care,,2020,2023,University of Toronto,77000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20448,202010PJK,Personality-Targeted Interventions for Addressing Polysubstance Use among Opioid-Addicted Clients Undergoing Opioid Substitution Therapy: A Feasibility Study,"We are amid a severe opioid crisis, worsened by the COVID-19 pandemic. In Canada, prescription opioid use and opioid overdoses/mortality were soaring pre-pandemic, reaching epidemic levels, with opioid-related deaths only increasing since the pandemic. Powerful and dangerous synthetic opioids (e.g., Fentanyl) are increasingly being used to cut street drugs given disruptions to the drug supply chain with pandemic border closures. More effective interventions for addressing opioid use disorder are sorely needed. An effective mainstay treatment for opioid use disorder in Canada is opioid substitution therapy (OST; e.g., methadone, buprenorphine). However, OST clients frequently have other problems that are not well served by OST alone such as high OST drop-out and continued polysubstance use during OST. The latter can include ""topping up"" with opioids, using substances that are dangerous when combined with OST (e.g., sedatives), and risky administration routes (e.g., injection). We have recently shown that personality traits that predict risk for mental health/behavioral problems also predict risky forms and routes of substance use in OST clients. We will use our expertise in brief cognitive-behavioral interventions and clinical research methods to test the feasibility of personality-targeted substance use interventions in OST clients. We are currently using our existing personality model along with interviews already collected from OST clients and service providers to adapt our personality-targeted interventions. For the proposed grant, in collaboration with our knowledge user partners, we will aim to try 4 personality-targeted interventions with clients across 4 OST clinics, evaluate feasibility, and provide a first test of their impacts on clients' polysubstance use and OST retention. We will examine feasibility from the perspectives of clients, therapists, and clinic directors to see if the personality targeted approach should be pursued further in this population. ",2020,2021,Dalhousie University,818779.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20449,202012MFE,"The association between COVID-19-related attitudes, concerns and behaviours in relation to Government policies (the iCARE Study): Optimising policy and communication strategies to improve health, economic and quality of life outcomes throughout the pandemic.","COVID-19 has caused a global public health emergency. While waiting for a vaccine, governments are using a number of policies that focus on changing people behaviour to stop the spread of the virus. However, for these policies to work and stop the spread of COVID-19 and improve the economy, people need to actually do (adhere to) the recommendations. For people to adhere to these policies they need: 1) to be aware of the policies; 2) see the policies as important; and 3) feel able to actually do the things they are being asked to do. All of these 3 things are influenced by where people are from, who they are, their current health, and the environment around them. Unfortunately, policies have changed over time and the exact polices and how people are told about the policies (messaging) varies greatly between and within countries. This has led to uncertainty among people about what is behind the government decisions and confusion about which policies to follow. The iCARE Study is a global survey that captures data on peoples' awareness, attitudes, and behaviours in relation to COVID-19 policies. We also ask how the pandemic is impacting peoples' physical and mental health, economic situation, and quality of life. In addition to over 70,000 survey responses, we collect data on number of cases and deaths, information about policies across different countries, and how people are moving about in their countries. These data will be linked and analysed together to understand which government policies are (or are not) influencing population behaviour, and in whom these policies are most or least effective. Of note, iCARE study has significant impact, and has been working directly with the government of Canada (supervisor Lavoie is on federal COVID-19 advisory board), as well as the governments of Ireland and Australia. ",2020,2023,Concordia University,580215.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20450,202012GSM,Understanding effective vaccination against severe acute respiratory syndrome coronavirus-2,,2020,2021,University of Ottawa,7700,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",,2020 +C20451,202012GSM,Investigating the Impact of the Great Recession (2007-2009) on Socioeconomic Inequalities in Blood Pressure in Canada using Distributional Decomposition.,"The Great Recession of 2007 to 2009 led to widespread unemployment and financial losses for families. Since income is a crucial determinant of health, the crisis may have led to adverse health outcomes. However, despite the abundance of research on the health impacts of the Great Recession, few studies have been conducted in the Canadian context and there appear to be inconsistent conclusions across disciplines. This inconsistency may exist because most studies use extreme measures of health (e.g., hypertension) which do not capture less severe but more pervasive health impacts. These subtle albeit widespread impacts can be examined by studying a population's distribution of a health outcome, such as blood pressure. However, a distributional approach has been absent in population health literature due to longstanding methodological challenges, until now. My proposed master's thesis will use a novel method known as distributional decomposition (DD) to evaluate changes in the blood pressure distributions of Canadians pre- and post-recession. I will use DD to quantify how much variation in income contributed to variation in blood pressure between 2007 and 2010. Quantifying the impact of income on variations in blood pressure distributions pre- and post-recession can inform effective policymaking to mitigate widening socioeconomic and health inequalities in Canada. This research is pertinent to the current socioeconomic climate as COVID-19 may lead Canada into another recession. My study is the first to use a distributional approach to investigate the health impacts of the Great Recession and will enhance our understanding of how economic crises impact socioeconomic disparities in health. ",2020,2021,University of Toronto,316614.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20452,202012GSM,"Evolution of Adherence to Effective COVID-19 Prevention Measures by High School Youth â€"" the Influence of School Events Related to the Pandemic",,2020,2021,Université Laval,13125,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20453,202011FBD,Brain white matter microstructure following SARS-CoV2 infection,"In the Spring of 2020, the lives of people worldwide have changed in unimaginable ways. Activities that were once deemed normal everyday activities now require careful consideration, weighing the potential risks against the benefits. Decisions are now made in regards to what is deemed safe, or of an acceptable level of risk, on a daily basis. In order to make these decisions, it is important to be fully aware of the impact that contracting the SARS-CoV2 virus can have on overall health. Importantly, several cases have been reported where SARS-CoV2 infection led to neurological symptoms including severe headache, nausea, loss of smell and taste, and even stroke. A large amount of evidence now shows that the virus can not only enter but also damage the brain, and, in some cases, this damage can prove to be fatal. Although there are known neurological complications to Covid-19, much remains unknown concerning the mechanisms at play. In this project, we will study the impact of Covid-19 on the brain, especially on white matter (the connective pathways between neurons) and cognition, using brain imaging techniques (MRI) and cognitive tests. We will also explore how risk factors, such as hypertension, diabetes, and smoking, influence the impact that Covid-19 has on white matter and cognition, as the presence of these risk factors has been shown to increase the risk of neurological complications with Covid-19. Neurological pathologies have a high incidence in Covid-19 patients, occurring in over one third of patients. These neurological complications lead to severe symptoms and high mortality rates. Our goal is to uncover the type of damage that can occur within the brain following SARS-CoV2 infection. We hope this study will be the first step in designing effective prevention and intervention programs to reduce the incidence and severity of neurological complications with Covid-19 in future research. ",2020,2023,Concordia University,78750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +C20454,202010PJT,RiseTx: A distance-based intervention for reducing sedentary behaviour among prostate cancer survivors,"Mounting evidence also suggests that extended bouts of sitting has deleterious associations with health outcomes in cancer survivors independent of physical activity. Cancer and its treatment together with the threat of COVID-19, has contributed to additional stress levels experienced by prostate cancer survivors. Therefore, supportive care interventions adapted to the pandemic among prostate cancer survivors are needed. Building on our successful pilot study, we will evaluate the effects of a 12-week intervention using wearable technology + behavioural counselling vs. wearable technology alone (control group) in reducing sitting time and increasing physical activity in prostate cancer survivors. We now propose an efficacy trial of RiseTx with some modifications to address the maintenance of the behaviour change we observed in the initial pilot. Maintenance of behaviour change was not a focus in the previous trial. As such, all components of the previous intervention including the RiseTx application and wearable activity tracker will be retained and we will provide additional behavioural support through videoconferencing to maintain behaviour change, which is an extension of our prior work. The intervention will consist of five phases consisting of behavioural counselling (e.g., goal setting, action planning) and daily step goals of 3000 (i.e., using an activity monitor; Fitbits) over the average of their baseline week at the end of 12 weeks. Prostate cancer survivors in the control group will receive Fitbits only with no further resources. This intervention has high potential for broad reach as it can ultimately be delivered through internet- and mobile-based applications. With internet usage growing fastest among older Canadians, our study will create a unique distance-based platform that could be scaled for use by clinical and community-based organizations as a low-cost, supportive care tool to improve quality of life for all cancer survivors.",2020,2023,University of Toronto,284006.25,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20455,202007MS1,I accompany COVID-19: a participatory action research project testing an innovative virtual support modality developed according to the model of compassionate communities in order to understand and prepare come complicated mourning in the context of a pandemic,,2020,2021,Université du Québec à Montréal,56750.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20456,202012GSM,Pandemic and access to food resources in Montreal: what impacts on vulnerable populations with food insecurity?,,2020,2021,Université de Montréal,13125,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20457,202011MM1,Covid-19 and infodemic: information practices of groups in a situation of vulnerability to COVID -19 in Quebec in the context of a pandemic.,,2020,2021,Institut national de santé publique du Québec,114750,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication,2020 +C20458,202010PJM,RESILIENCE (RESponsive Inquiry Linking IntervENtions and Caregiving Experiences),"Family and friend caregivers, two-thirds of whom are women, play an essential role in supporting the 500,000 Canadians living with dementia. Interventions are available to support family and friend caregivers experiencing adverse mental health outcomes such as burden or depression related to their caregiving role (e.g. exercise, psychotherapy, education, respite care); however, many of these interventions have not been directly compared in randomized trials. This makes it challenging for caregivers, clinicians, and policy makers to know which interventions will work the best in reducing these adverse mental health outcomes for family and friend caregivers. We will review the literature and identify all randomized trials describing the efficacy of in person and virtual interventions (e.g. by telephone or videoconference) for improving: symptoms of burden, distress, depression, anxiety, and loneliness; quality of life; and knowledge and caregiving skills of family and friend caregivers of people with dementia. This will be the first study of its kind to understand which interventions for family and friend caregivers of people with dementia will work the best and how these interventions might better support family and friend caregivers. We will identify interventions that will work better for different groups of caregivers (e.g. older women, older men). This work will support the feasible implementation of evidence informed in person and virtual interventions that are tailored to the needs of family and friend caregivers during and after the COVID-19 pandemic. ",2020,2021,Unity Health Toronto,75000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20459,202012ID1,The Impact of the COVID-19 pandemic on youth substance use problems and services: Knowledge synthesis with Indigenous Nations and organizations.,,2020,2021,McGill University,75000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2020 +C20460,202012GSM,Optimizing an Online Couples PTSD Self-Help Treatment,"Cognitive-Behavioural Conjoint Therapy (CBCT) is an efficacious couples therapy that targets posttraumatic stress disorder (PTSD) and relationship satisfaction. However, there are significant barriers to accessing CBCT, including additional barrier from the COVID-19 pandemic. To increase accessibility an online, therapist-assisted couples self-help intervention was modelled after CBCT, Couple HOPES (CH). Generic couples therapy and CBCT literature suggest that initial relationship satisfaction may moderate treatment outcomes and predict dropout. Determining if preintervention relationship satisfaction moderates outcomes in CH is imperative to ascertain if it is an effective treatment alternative for couples with both high and low relationship satisfaction. The proposed study aims to examine the effects of preintervention relationship satisfaction on PTSD, relationship satisfaction and dropout in CH. The proposed project will utilize data from a larger funded trial. Military members, veterans, first responders, and healthcare workers exposed to COVID-19 with PTSD and their significant other (N = 140) will be receive access to 7 CH modules and 4 brief therapist calls. Self-report measures will be administered at pre, mid, post, and follow up. PTSD will be assessed with the PTSD Checklist for the identified patient and the PTSD Checklist Collateral version for the partner. The Couples Satisfaction Index will assess each partners' relationship satisfaction. PTSD and relationship satisfaction outcomes will be analyzed using growth curve modelling. Dropout will be analyzed with a continuous time survival analysis. These findings have clinical implications for maximizing outcomes by paring couples with the most suitable intervention based on their relationship satisfaction. ",2020,2021,Ryerson University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20461,202012GSM,Access to Healthcare by Socially Vulnerable Persons during the COVID-19 Pandemic: An exploration of race and intersectionality,"Although the Canadian Medicare system was created to make sure that everyone has access to affordable healthcare, some people fall between the cracks. The Covid-19 pandemic has drawn attention to health and healthcare disparities that can't be ignored. In Montreal, Quebec, the largest number of Covid-19 cases are reported in neighborhoods with high rates of poverty and the most racial diversity. Although over 22% of the Canadian population identify as a non-white visible minority, unlike the USA, racial/ethnic differences in health and access to healthcare are not commonly discussed. In this study, we will explore the experiences of racialized minorities in accessing primary healthcare during the pandemic in multicultural neighborhoods in Montreal. We will talk with different racialized groups to understand their healthcare needs and challenges in accessing care and discuss our findings with family doctors to identify strategies to promote cultural safety and access. Without research that directly addresses race-based differences in the Canadian healthcare system, it is likely that the inequities in healthcare access that have been seen during the pandemic will continue. ",2020,2021,McGill University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +C20463,202012GSM,Canadian Self-Employed Experience in Returning to Work Following Cancer,"Nearly one in two Canadians will be diagnosed with cancer at some point in their lifetime, but due to advances in early detection and treatment, mortality of cancers is on the decline with over 60% of those diagnosed with cancer surviving. Self-employed cancer survivors remain an understudied group with the majority of the literature focusing on salaried cancer survivors, despite self-employed workers accounting for 15% of the Canadian workforce. The lack of research on self-employed survivors means that the barriers and facilitators of remaining or returning to work following cancer remain relatively unknown. The study will be completed by interviewing 25 Canadian self-employed cancer survivors who have remained or returned to work following a cancer diagnosis. Data will be collected during semi-structured phone or zoom interviews of 45 to 60 minutes will be conducted guided by the Vocational Rehabilitation Model for cancer survivors. Interviews will be transcribed verbatim and a continuous, comparative method will be used to code and analyze data of the 25 interviews. The goal of the study is to describe the unique experiences and strategies of self-employed Canadian cancer survivors with remaining or returning to work following cancer. Interviews will explore (1) the overall experiences while remaining at or returning to work; (2) work-related barriers and facilitating factors while remaining at or returning to work; (3) work accommodations employed to address the barriers; and (4) the impact of COVID-19 on cancer survivors ability to remain or return to work. The analyzed data will be used to develop future interventions to support self-employed cancer survivors with remaining or returning to work following cancer. ",2020,2021,McGill University,13125,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +C20464,202010PJT,Young immigrants and refugees co-designing mental health and well-being solutions,"Canada is home to hundreds of thousands of immigrants and refugees, a large portion of which are young people. A successful settlement experience for young immigrants and refugees (YIR) is vital for the future of the country. However, YIR can face many barriers (e.g., school adjustments, social challenges, employment, housing, financial, and linguistic), in addition to racism and discrimination. These barriers can negatively impact mental health (MH) of YIR. The COVID-19 pandemic has exacerbated the issue, with MH challenges increasing for YIR. Without appropriate culturally sensitive services and supports directed at prevention or early-intervention, MH challenges will persist, becoming more severe mental disorders that are harder to treat and have long lasting consequences. It is time to re-imagine what is available for YIR and move beyond a one-size-fits all approach to create culturally sensitive services/supports, inclusive of eMental Health (eMH) options, that focus on prevention and early intervention for YIR MH and well-being. The aim of this 4-year study is to build awareness and enhance the MH and well-being of YIR in Manitoba (MB). YIR will be interviewed about their MH experiences, needs, and ideas for possible culturally sensitive solutions, as well as take part in photovoice, focus groups, and eMH workshops. YIR parents and key stakeholders from community-based organizations will also be interviewed. Short-term, the knowledge gained of YIR MH experiences and needs will be used to promote awareness of YIR MH and well-being. Concrete solutions for community-based services and supports will result for MB but also for sites across the country that can be tailored to specific YIR populations. This project will also result in a culturally sensitive, interactive eMH self-management prototype. Long-term, the culturally sensitive, interactive eMH prototype will be available for scaling up in other sites across Canada. ",2020,2024,University of Manitoba,570882,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20465,202012MFE,High-Throughput Heart-on-a-Chip Platform for Studies of SARS-CoV-2 Induced Myocardial Injury,"Recent study reported that 78% of the patients recovered from COVID-19 have cardiac involvement and 60% of the patients have ongoing myocardial inflammation based on cardiac magnetic resonance imaging. However, the direct contribution of SARS-CoV-2 infection on the beating cells types of the heart, cardiomyocytes, versus supporting cells that makeup the blood vessels and the matrix as well as immune cells homing to the heart after the infection are not well understood. Human stem cell derived heart-on-a-chip models afford the most direct and efficient route for answering these questions. My preliminary data collected in the CL3 facility demonstrate profound and progressive loss of contractile ability in my heart-on-a-chip platform upon SARS-CoV-2 infection. Stem cell based heart-on-a-chip model is additionally unique as it enables us to systematically study infection on different cell types that make up the heart, an experiment that is not possible in vivo. I will first scale up the production of the heart-on-a-chip platform using 3D printing. I will situate this platform in a 24 well plate, a setting that is suitable for working in biohazard level 3 facility. After infecting the human heart tissue with SARS-CoV-2, I will non-invasively measure how the contractile force changes with time. At the same time, I can collect culture media and determine the extent of inflammation. Through electron microscopy, I will visualize the virus in the human heart tissue. Therapies for covid19 infected heart currently do not exist. I hypothesize that extracellular vesicles derived from healthy cells could represent a viable biological therapy. These consist of a rich mixture of micro RNAs and proteins that are known to be able to protect the heart in other settings, such as loss of oxygen. I will isolate these EVs from healthy cells and apply them to the infected heart-on-a-chip to study preservation of beating function and subsequent improvement. ",2020,2022,University of Toronto,67500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2020 +C20466,202012GSM,The Effect of Socioeconomic Inequalities on Adolescent Health During COVID-19,,2020,2021,McMaster University,13125,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20467,202012GSM,COVID-19 and Spinal cord injury: The impact of societal lockdown on healthcare utilization and costs for individuals with lived experience,,2020,2021,University of Toronto,13125,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +C20468,202012GSM,Resilience and coping mechanisms among children during COVID-19: A mixed-methods study grounded in attachment theory,"The COVID-19 pandemic is an adverse experience for many, especially children. It is imperative that we strive to increase knowledge surrounding resiliency and healthy coping mechanisms of children, abilities that if used amidst stressful experiences, are attributed to favourable maternal attachment styles. As such, the proposed mixed-methods, cross-sectional study has three objectives: (1) to examine the impact of the overall COVID-19 pandemic on the resilience of elementary school children; (2) to explore the relationship between maternal attachment style and subsequent resilience; and (3) to determine coping mechanisms employed by children during the COVID-19 pandemic. To achieve this, 197 students grades 3-6 and their mothers will be recruited through the Thames Valley District School Board. To be eligible for the study, mothers must have at least one child attending an elementary school within the school board between the grades of 3-6 and be proficient in English. Children and their mothers will complete complementary online surveys via Qualtrics, inclusive of demographic information and a total of five validated questionnaires to measure attachment styles, resiliency, and coping mechanisms. Upon conclusion of the survey, children will audio record a response to an open-ended question regarding their overall experience of resiliency during COVID-19. Data analysis conducted in RStudio will compute measures of central tendency, dispersion, and correlational relationships between variables. Interpretive description will be performed on qualitative data. Findings from this study aim to inform how educators and parents can best support and understand children's resiliency amidst adverse circumstances, including the eventuality of future pandemics. ",2020,2021,Western University,13125,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +C20469,202012MFE,Opioid Agonist Therapy Amidst the Overdose Crisis and the Novel Coronavirus (COVID-19) Pandemic: Attitudes and Access,,2020,2023,University of Toronto,123750,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",,2020 +C20470,202102HI5,Establishing a Culture of High-Value Healthcare within the McGill University Health Centre Department of Medicine: a Focus on Evidence-based Practices in COVID Care,"The MUHC is a major health network affiliated with McGill University, one of the most respected medical institutions in Canada. The DOM is entering its fifth year of operations and is responsible for leading research projects in the hospital related to patient safety and improving the quality of care. Most recently, a major focus has been placed on COVID-19 patient care. Our proposed program will focus on developing ""high-value"" healthcare projects, supported by the HSIF Fellow, who has extensive research training. The fellow will help design new projects and expand existing projects. Our goal is to promote and embed a culture of standardized, high-quality care for medical patients. We will accomplish this with technological solutions (for example e-learning modules) and strengthening research activities at the MUHC (encouraging and supporting scientific publications). We will focus on improving health outcomes for MUHC patients with COVID using digital solutions. For clinicians caring for patients with COVID, we will develop effective in-job training and offer a formal education program with modules on patient safety, quality improvement, and the appropriate use of tests and treatments. These will be delivered to doctors and nurses effectively using information technology and will be founded in scientific evidence. Our program is designed to achieve our objectives in three steps: 1) the assessment phase- a ""needs"" assessment; 2) the refinement, implementation, and development of the solution phase; and 3) the monitoring, evaluation, and strengthening phase. Our approach will adopt an agile and innovative strategy: for each project, we will address the key pillars of high-value healthcare: patient safety, quality of care, and optimal use of resources; digital technologies; the patient experience; and ensuring evidence-based practice. By working together with the HSIF Fellow, our institution can have a greater impact on the safe and effective care of our patients. ",2021,2023,McGill University,38315,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health workforce",2021 +C20471,202104PJT,"Improving Public Health Finance Capacity and Spending Data Monitoring and Reporting to Inform the COVID Recovery Period: An International, Sequential Mixed-Methods Investigation",,2021,2024,Carleton University,368653.5,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +C20472,202103CRP,Identifying changes in cancer risk factors during the COVID-19 pandemic and predicting population risk,,2021,2023,McMaster University,44437.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20473,202109POC,Motivational interviewing to promote healthy behaviours for obesity prevention in young adults: a pilot randomized controlled trial,"Need for project Obesity is an established risk factor for many cancer types, including colon, endometrial, breast, and pancreatic. Obesity is complex and treatment is challenging. Thus, primary prevention of obesity is important. This is particularly important now since the COVID-19 pandemic had a profound impact on many obesity risk factors, such as chronic stress, overeating, and physical inactivity. Early adulthood is a key period in obesity development and a critical period for prevention interventions. Goal of project The overall goals of this project are to evaluate the feasibility of web-based nurse-led motivational interviewing and educational interventions to promote healthy behaviours for obesity prevention and maintenance of healthy weight and behaviours among young adults attending university (age 18-29) in Hamilton, Ontario. A secondary goal is to evaluate if the intervention is more successful among people at higher risk of obesity (a risk stratification approach). Project description A pilot randomized controlled trial will be conducted. Young adults will be randomized to receive a tailored behavioural intervention through motivational interviewing sessions with a nurse combined with educational materials, or control (educational materials only). Both groups will be followed for 6 months and feasibility and clinical outcomes will be measured. Future impact Prevention of obesity and promotion of healthy weights and behaviours has the potential to positively impact primary prevention of cancer among Canadians. The results of this study will generate new evidence to support the delivery of a tailored obesity prevention intervention. The results of this study will inform the design of future larger studies and ultimately the development of new policies for the implementation of clinical or public health interventions to help stop cancer before it starts. ",2021,2022,McMaster University,77336.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20474,202104PJT,Understanding the impact of the COVID-19 pandemic on obesity and diabetes among Canadians; a prospective population-based cohort study,,2021,2026,McMaster University,586219.5,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20475,202112GSM,Investigating ORF8-mediated immune evasion in SARS-CoV-2 variants of concern,,2021,2022,McGill University,13825,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20476,202110QAE,Direct Funding and Health Equity in Dementia Care: Evaluating a New Direction in Service Delivery,"Before COVID-19 health systems were strained and people living with dementia on continuing care waitlists and their caregivers were in crisis. This crisis was intensified with the pandemic. In July 2020, the Government of Nova Scotia expanded the Supportive Care Program as part of its pandemic response and to support people living with dementia to remain at home rather than in hospital as they waited for home care or long-term care. The program provides people living with dementia who have a caregiver that helps them with decision making and who are on the waitlist money to purchase personal care, respite, housekeeping and meal preparation. In giving people who are in a vulnerable situation money to purchase their own services, the program offers an innovative approach to continuing care service delivery. By supporting care at home, it has potential to enhance the quality of care of people living with dementia and improve the health and well-being of people living with dementia and their caregivers, as well as relieve some of the strains on the system that can drive costs, and influence the working conditions of care providers. While there is potential, evidence is still lacking. We do not know much about the program from the perspectives of people living with dementia, their caregivers and home care providers. We also do not have a strong understanding of whether there are differences in how people learn about, access and experience the program. In this project we will talk with people who are using, providing, planning, and sharing information about the Supportive Care Program to better understand its real and potential value. In doing so we will create new knowledge and share what we learn with the public, providers and policy makers to support better care and a stronger health system.",2021,2022,St. Francis Xavier University,78495.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20477,202104PUU,Pregnancy and COVID-19 hospitalization in Quebec,"There is still a lot we do not know about risk factors and outcomes of COVID-19. Recent information suggests that pregnant women with COVID-19 have a higher risk of problems such as preeclampsia (high blood pressure), preterm birth, and being admitted to an intensive care unit. Children with COVID-19 are at risk of an inflammatory syndrome where multiple organs have a hard time working properly. It is possible that diseases at earlier points in life can help identify women and children at risk of COVID-19 disorders. A woman's health during pregnancy may indicate the risk of health problems later on for both her and her child, and may also help estimate their risk of severe COVID-19 disease. In this study, we will identify the medium and long-term outcomes of COVID-19 infection during pregnancy. We will also identify health characteristics earlier in the lives of women and children to see if they are associated with future COVID-19 severity. We will use a large dataset containing all mothers and infants born in hospitals in Quebec, Canada. We will follow women and children over time until the start of the pandemic. We will then identify women and children who developed a COVID-19 infection. We will determine if mothers and children exposed to problems like preeclampsia and preterm birth before the pandemic have a greater risk of severe COVID-19 infection during the pandemic. For women who had COVID-19 during pregnancy, we will follow them and their newborns for up to 1 year after delivery and examine their risk of hospitalization for persisting health problems. This project will help determine if health during pregnancy before the pandemic can be used to identify women and children at greater risk of a COVID-19 infection. The study will also help doctors better care for mothers and children who were exposed to COVID-19 infection during pregnancy by assessing their risk of health problems in the years after delivery. ",2021,2024,Institut national de santé publique du Québec,355500,Other,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +C20478,202112GSM,Online Peer-Delivered Group Cognitive Behavioural Therapy for Postpartum Depression,"Postpartum depression (PPD) is one of the most common complications of childbirth, affecting up to 20% of mothers in the first year after delivery. If untreated, it can have negative effects on the mother, their partner, their newborn, and the other children in the family. Unfortunately, just 1 in 10 mothers with PPD are able to get the treatments they most want and need (e.g., talking therapies), a situation that has worsened during the COVID-19 pandemic. As a result, innovative, sustainable, and engaging options that safely provide treatment to large numbers of mothers are urgently needed.The purpose of the proposed study is to test the effectiveness of an Online 9-Week Cognitive Behavioural Therapy (CBT; a type of talking therapy) program delivered by mothers who themselves have recovered from PPD (i.e., lay peers). We will recruit 174 mothers who currently have PPD and infants 12 months of age. Mothers will either receive group CBT plus treatment as usual (TAU) from their usual healthcare providers or TAU alone. This study will determine if this online group treatment can lead to stable improvements in PPD, maternal anxiety, parenting stress, their relationships with their partner and infant, and infant temperament. We believe that this peer-delivered treatment will improve PPD and its accompanying difficulties, as well as reduce its adverse effects on families in a cost-effective manner.In addition to the suffering that PPD imposes on mothers and families, the financial cost of untreated PPD may be as high as $150,000 per case over the lifespan. If effective, peer-delivered group CBT for PPD could provide the healthcare system with an affordable and scalable treatment that can improve the health of mothers and families during the pandemic and beyond. ",2021,2022,McMaster University,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20479,202108VCF,"Best practices for community-led strategies to boost vaccine confidence: A case study in Parc-Extension, Québec","The most racially diverse and socio-economically disadvantaged neighbourhoods in Canada, primarily those concentrated in large urban areas such as Parc Extension in Montréal, Québec experience have been vaccinated at lower rates despite availability. The lower vaccination rate among residents in Parc Extension is attributable to vaccine hesitancy, characterized by uncertainty and ambivalence about vaccination, a legitimate viewpoint, underscoring the failure or lack of an effective public health system. In response, new and reimagined vaccine interventions that are community-led, culturally-relevant, and place-based have been developed in Parc Extension to successfully increase vaccine confidence and uptake. There is a clear need for better quality studies on the use of community-led vaccination strategies in promoting confidence, particularly in low income and diverse regions in Canada, where research capacities are limited. This proposed community-based research has the fundamental goal of producing qualitative evidence guided by grounded theory using Parc Extension, Québec as a case study in understanding dynamic community-led responses and developing a best practices implementation toolkit to address vaccine hesitancy. Semi-structured interviews will be conducted with diverse key stakeholders in Parc Extension to understand the best practices required to establish successful and effective community-led vaccine strategies. Data will be analyzed using open-coding and synthesized member-checking to develop a best practices toolkit to implement sustained effective community-led strategies to achieve vaccine confidence among low income and racialized communities in Canada. ",2021,2023,McGill University,151932.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20480,202110MFE,Investigating the impact of vaccination status on innate immune responses to SARS-CoV-2 Variants of Concern (VOCs),,2021,2024,"Sunnybrook Research Institute (Toronto, Ontario)",106650,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C20482,202112WGC,COVID-19 pandemic and its impact on Alzheimer's care,,2021,2021,"CIUSSS du Centre-Sud-de-l'Île-de-Montréal (Montréal, Québec)",0,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20483,202112GSM,Antibody-dependent cellular cytotoxicity against SARS-CoV-2 variants of concern,"In December 2019, several pneumonia outbreaks emerged in China, all related to the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The high transmissibility of SARS-CoV-2 caused the current devastating pandemic of coronavirus disease 2019 (COVID-19). Through a collective effort, around 7 billion vaccine doses were administered worldwide as of November 2021 and demonstrated high levels of protection against infections and severe cases of COVID-19. Most vaccines deployed target the spike (S) glycoprotein. The S protein is exposed at the surface of viral particles and infected cells. Its role is essential as it is the ;viral entry key allowing it to attach and enter cells to replicate. Antibodies generated by vaccination can block this interaction, preventing the virus from replicating; this is called neutralization. SARS-CoV-2 is under tremendous selective pressure, particularly for the S glycoprotein, resulting in the appearance of mutations. Recent studies have shown a significant loss of neutralization against emerging variants of concern (VOCs), such as the Alpha, Beta and Delta variants. However, the vaccine remains effective against severe cases, suggesting that vaccine protection is not solely due to neutralization. Antibodies also play a crucial role in eliminating SARS-CoV-2 infected cells through Fc-effector functions including antibody-dependent cellular cytotoxicity (ADCC). We therefore believe that individuals who developed antibodies with little to no neutralizing activity will stay protected against SARS-CoV-2 and maintain this resistance across emerging VOCs through ADCC. Our studies will help determine the humoral correlates of protection against SARS-CoV-2. ",2021,2022,Université de Montréal,13825,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C20484,202104GA7,Prevention is better than cure: the arts as vehicles for knowledge transfer and exchange (KTE) in public health in the context of a pandemic,,2021,2022,Université du Québec à Rimouski,101672.21,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,,,2021 +C20485,202109PJT,Upstream determinants of effective COVID-19 response: learning from comparisons across Canada's provinces,"We will contribute new knowledge to improve the public health response to emergencies such as COVID-19. This research uses a mixed-methods case study approach with an innovative focus on how upstream determinants: institutions, politics, organization, and governance (IPOG) influence governments' effective activation of public health systems and capacities during a crisis. Better understanding of the effects of IPOG factors will complement current research on interventions to address this pandemic and contribute to efforts to reduce disparities in outcomes. This study incorporates key CIHR priority interests in research to strengthen public health systems in Canada and spans across four provinces: British Columbia (BC), Ontario, Quebec, and Nova Scotia. Province-specific analyses will be carried out followed by a comparative analysis to develop more generalizable findings. These provinces represent a broad cross-section of Canadian geography, differences in province-level health systems, COVID-19 response, and other relevant socio-economic factors. The results will be useful to improve laws, regulations, and organizational capacity to respond to public health crises and to national efforts to support these and other provinces. Previous work by several partners has demonstrated the feasibility of this research. We will build on the organizational analyses of public health systems in Canada conducted by the North American Observatory on Health Systems and Policies; the ongoing data collection of the IPOG case study in BC; and research on interventions and implementation led by the Co-I's at Dalhousie with other Canadian partners, all sponsored by CIHR. These methods will be further adapted to specific provincial contexts and cross-province comparison. Each province-based team has identified knowledge partners in their jurisdiction who will contribute to the research and assist in dissemination and knowledge translation in provinces and nationally. ",2021,2023,University of British Columbia,483480,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2021 +C20486,202104PJT,"The right care, for the right patient, at the right time, by the right provider: A value-based comparison of the management of ambulatory respiratory diseases in walk-in clinics, primary care physician practices and emergency departments","Emergency departments (ED) are specialized and costly public health services. Designed to provide care for patients with urgent or life-threatening conditions, they continue to treat large numbers of low-acuity ambulatory emergency patients (consulting for health issues that do not require being kept for observation on a stretcher). An estimated 30-60% of all patients treated in these services belong to this category, which some analysts regard as a source of emergency department overuse or misuse. Others argue that patient evaluation in the ED may be more cost-effective. The debate has been complicated by the COVID-19 pandemic, which has shifted primary care practices and walk-in clinics significantly towards telemedicine (remote or virtual consultation by phone or videoconferencing), presumably a more convenient and efficient consultation modality under the circumstances. As healthcare expenditures continue to rise, the most efficient care pathways must be identified and strengthened in order to ensure sustainable healthcare systems for all Canadians. By comparing the value (i.e. health outcomes and costs) of care given (in person or by telemedicine) in EDs, walk-in clinics and primary care practices for ambulatory emergency patients presenting with acute respiratory conditions, our research project will enable decisionmakers and policymakers to: 1) determine the most efficient care settings for this patient category; and 2) promulgate value-centred reforms whereby ambulatory patients with acute unexpected needs will receive the best urgent care at the lowest cost. We believe that this will represent a major contribution to the sustainability and adequacy of publicly funded Canadian healthcare and allow it to fulfil its mission of improving the health of the population. ",2021,2024,Université Laval,695003.29,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C20487,202104PJT,Study of the eco-efficiency of wearing personal protective equipment against COVID-19 in emergencies for a post-pandemic context,,2021,2023,Université Laval,126913.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +C20488,202102VS1,COVID-19 Variant Supplement - Gender and addiction intervention in the context of a pandemic with people in a precarious social situation,,2021,2022,Université de Sherbrooke,39500,Unspecified,Unspecified,Unspecified,Unspecified,Drug users | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +C20489,202112GSM,Age-related changes to lymph node microarchitecture and impacts on T cell responses,"The COVID-19 pandemic has illustrated that elderly people are at much higher risk of developing severe symptoms from infection. This is partly due to reduced responsiveness of T cells, a type of immune cell that protects the body from foreign invaders, such as bacteria and viruses. It is known that T cell responses become less efficient with age, but whether changes to the immune environment in older people can impair T cell responses is incompletely understood. For T cells to effectively patrol all areas of the body, they are constantly commuting between different secondary lymphoid organs in which they can encounter infectious agents. T cells spend much of their time travelling along a network of roads within lymphoid organs created by fibroblastic reticular cells (FRCs). However, FRCs may become stiffer with age, which increases the amount of force they exert back on T cells. In response to greater external forces, cells increase the rigidity of their nucleus, which houses their genetic material. If cells cannot adapt to the higher pressure surrounding them, their genetic material will be damaged, causing them to lose their function. Consequently, T cells must adapt to different types of terrain to navigate efficiently and not harm any of their inner machinery. Although, as T cells age, they become ;rusty and may struggle with this adaptation. The goal of my research is to uncover how the structure and physical properties of FRC networks change with age and how aged T cells migrating through the network respond to these alterations. Understanding how T cells are affected by their environment will allow us to develop therapies that can restore immunity in older individuals and ultimately reduce the burden of infections and other diseases on the elder population. ",2021,2022,McGill University,13825,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +C20490,202112GSM,Integrating T-Cell Contraction Phase Into a Mathematical Model for Vaccine Immune Response & Immune Memory,"To prevent complex infections like HIV-AIDs, malaria, and COVID-19, the next generation of vaccines will need to stimulate all branches of the immune system, not just antibody-based ;humoral immunity. In contrast ;Cellular immunity comprises various T-cell subtypes that when activated by pathogen molecules can seek and destroy individual infected cells, refocus the immune response towards addressing the unique threats posed by the pathogen, and remain in circulation decades after infection to provide a rapid response to variants of the original invader. However, the interaction of multiple factors surrounding T-cell activation can lead to profound differences in response success and cell fate, providing significant uncertainty when researchers try to design vaccine formulas to elicit specific results. Computer models can provide clarity by simulating these factors, tracking millions of cell-cell interactions in a way that is difficult or even impossible in experiments. Our research group has created the first probabilistic simulation of the immune response to vaccine injection. My project aims to expand the model to predict the end of the immune response, where T-cell numbers drop to leave a reserve of memory cells. I will use data from literature and our collaborators to codify the genetic and metabolic timing that governs T-cell replication and lifespan, as well as relating these population-level changes to factors that surround the early activation of a handful of cells. Thus, the model will be able to predict complex T-cell dynamics from a few early interactions, providing necessary information that can determine the best dosage and scheduling of vaccines to ensure an appropriate immune response to infection with a capable reserve of memory cells for the future. ",2021,2022,McMaster University,13825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20491,202110QAE,Choosing the right model of care together: Shared decision making to improve equitable implementation of in-person vs virtual care for youth with chronic pain and their families,"Chronic pain (pain lasting months to years) affects one in five youth in Canada. This pain can last into adulthood and negatively impacts an individual's mental health, their well-being, and their ability to earn a living. The COVID-19 pandemic is making chronic pain worse because it is harder for youth and their families to access healthcare. As a result, medical appointments now mostly happen by telephone or video (called virtual care) instead of in person. This helps a lot of people, but makes it harder for others who already struggle to access chronic pain care, such as youth who identify as Black or of colour or have brain-based developmental disabilities (like Autism or Cerebral Palsy). We want to make sure that all youth with pain and their families have a say in whether they receive their pain care in person or virtually. We will do this by creating a tool called a decision aid that makes it easier for youth, their parents, and healthcare professionals to decide together whether in-person or virtual care is best. Our project will complete four related activities to create this decision aid. We will: (1) review what we already know about which treatments for chronic pain are most helpful in person or virtually; (2) survey clinics for youth with chronic pain in Canada and around the world about how they are making this decision right now, (3) ask diverse youth with chronic pain, parents, healthcare professionals, and administrators about what information they want included in the decision aid; and (4) create the decision aid with our team of youth, parents, healthcare professionals, and administrators and make sure that they think it is acceptable. The decision aid we create together will make sure that diverse youth, their families, and healthcare professionals have a positive experience of care for chronic pain, make sure that youth get the best pain care they need, and reduce unnecessary costs for families and the health system. ",2021,2022,University of Calgary,78996.84,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20492,202102SMP,Social inequalities in aging in place and access to health and social care,"The Canadian population is aging rapidly, and more than 17% of Canadians are now aged 65 or older. Although many older adults live with functional limitations and chronic diseases, most prefer to remain in their homes as they age rather than transition to long-term care facilities (""aging in place""). In this context, timely access to health and social services is critical for older adults who are facing challenges maintaining their autonomy at home. Without these resources, older adults are more dependent on emergency care and are more likely to be hospitalized and subsequently admitted to long-term care. Despite universal healthcare coverage in Canada, social inequalities in access to healthcare and social support remain prevalent, creating disparities in the ability to age in place among certain populations and leading to health inequity in older age. The objectives of my doctoral research are to evaluate how inequalities in admissions to long-term care, hospitalizations and emergency care use in older age are influenced by gender, socioeconomic position and rurality, and to examine the mediating impact of having access to health services and social support in reducing or perpetuating these inequalities. The results of my research will contribute to a better understanding of the social inequalities of aging in place and inform public health action and policy decisions aiming to reduce inequalities in healthy aging. The importance of such policies and practices is increasingly relevant with the growing population of older adults. Furthermore, the urgent need to improve care infrastructures for older adults has been highlighted by the disproportionate effect of the COVID-19 pandemic on older adults living in long-term care settings in Canada. As we enter the UN Decade of Healthy Aging (2021-2030), strategies to foster the autonomy and dignity of older adults are essential determinants of equitable health in older age.",2021,2022,McGill University,0,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20493,202109PAA,"Impact of the COVID-19 Pandemic on Type 2 Diabetes Incidence: Finding synergy among science, policy, and action","The pandemic has placed an unprecedented strain on our society. While public health measures have been effective in flattening the curve to reduce COVID-19 infections, they have led to widespread reductions in physical activity and an increase in snack food consumption. These changes, combined with ongoing stress from social isolation, job losses, and financial strain, may have negative consequences for our health. We suspect that there will be a rise in body weight in the population, causing more people to develop diabetes. Our team will use population health data from Ontario and advanced statistics to study whether the number of people who develop diabetes increases during the months and years following the pandemic, and which subsets of the population (e.g. women versus men, lower versus higher income groups) will be most affected. We will also test whether the intensity and duration of lock-down measures and unsupportive neighbourhood environments (e.g., fewer opportunities for physical activity and healthy eating) contribute to the rise in diabetes incidence, particularly in low income and racialized communities. This work will be vital for identifying potential policy scenarios to avert diabetes cases and reduce healthcare costs. With input and guidance from our multisectoral policy and community engagement committee we will identify potential solutions and create an action plan that will reduce the burden of diabetes in areas impacted the most. Collectively, this research program will provide critical information to guide decisions regarding which public health policies have the greatest potential to improve the health and wellbeing of Canadians, by 'flattening the curve' of diabetes. ",2021,2022,Unity Health Toronto,79000,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20494,202112GSM,Examining quality of life among those with adjustment disorder and post-traumatic stress disorder in the context of the COVID-19 pandemic.,"The COVID-19 pandemic has introduced unprecedented levels of stress into the realities of daily living. Many of these stressors, such as job loss and quarantine practices, are of a non-traumatic nature. However, due to threats such as loss of life, some may experience stress of a traumatic nature. The traumatic nature of such high-intensity stressors has the potential to influence the onset of pandemic-related mental health disorders such as adjustment disorders (AD) and post-traumatic stress disorder (PTSD) in some portions of the population. Because the onset of pandemic-related AD and PTSD are relatively new phenomena, little is known about the impacts of these disorders on reported quality of life (QOL) within this context. Thus, it is crucial to further investigate QOL outcomes in relation to pandemic-related AD and PTSD to first foster a greater understanding of the implications of stressor-induced mental health disorders on QOL and to then inform the development of effective interventions for future similar events. This study first seeks to accomplish these goals through the direct administration of a diagnostic tool and self-report quality of life measure to a sample of 200 Canadians. The results of this data collection will be analyzed in a variety of contexts to examine for relationships and differences between QOL outcomes in those with no diagnosis versus those with diagnosable AD or PTSD. Additionally, analyses will examine if these groups report significant differences in any of the four major facets of QOL (physical health, psychological, social relationships, environment). Results of this study will provide a relevant insight into the implications of a mental health disorder on QOL outcomes in the context of a mass-stressor event such as a pandemic. ",2021,2022,McGill University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20495,202109EG4,Prioritization of intensive care in an extreme pandemic context: 1) modeling/simulation of different strategies for prioritizing access to intensive care and 2) democratic deliberations of the parties stakeholders on the values ​​underlying the models and their health impacts.,,2021,2022,Université de Montréal,165471.03,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Health Systems Research,Impact/ effectiveness of control measures | Health service delivery,2021 +C20496,202111FBD,Peripheral Inflammatory Disease (COVID-19 and Inflammatory Bowel Disease) and Brain Gliosis,"Inflammation is the body's natural response to infection or injury, like the redness that happens around a scrape on the skin. In conditions where inflammation is very active, it is possible for the inflammation to affect the brain. This is especially seen in two conditions where clinical depression occurs very frequently: COVID-19 and inflammatory bowel disease (IBD). After recovering from COVID-19, approximately 15% of people experience clinical depression. Similarly, depression occurs three to five times more frequently in people with IBD than in the general population. Unfortunately, there are no treatments designed for depression from COVID-19 and IBD because little is known about how inflammation affects the brain in these conditions. We think that inflammation from other parts of the body spreads to the brain in COVID-19 and IBD, but this has not been studied yet. Using new brain scanning methods, we are able to measure levels of inflammation in the brain. In our previous research, we used these methods to show that brain inflammation occurs in clinical depression and that higher levels of inflammation may lead to more severe depressive symptoms. And now, our new data shows that these levels may be higher in COVID-19 and IBD. Brain scans in a few people that have recovered from COVID-19 showed a 15% to 30% increase in inflammation and a brain scan in one person with IBD showed an increase over 50%. In our new study, we propose scanning more participants with these conditions to see if brain inflammation is consistently higher than in the general population. If this is the case, then medications that can reduce inflammation in the brain may be effective in treating depression caused by inflammatory diseases like COVID-19 and IBD. In fact, there are already some medications available for other illnesses that can reduce brain inflammation, they just need to be tested for other purposes. ",2021,2024,Centre for Addiction and Mental Health (Toronto),82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20497,202109PJT,Parent-mediated intervention for toddlers with autism: A multi-site randomized controlled trial of a group-based virtual program that empowers parents as change agents,"This project uses a rigorous research design to evaluate an innovative early intervention program for toddlers with autism spectrum disorders (ASD). The program builds on an evidence-based in-person model (Social ABCs) that uses direct in-the-moment coaching to help parents learn skills to support their toddlers' development. Significant barriers exist to accessing early ASD-specific interventions, including long wait lists due to limited system resources (eg. insufficient funding to meet caseload, lack of sufficient skilled workforce), exacerbated by restrictions to in-person care associated with families' distance from service centres, and now COVID-19 isolation measures. In response to these pressures, we adapted the intervention to increase efficiency and access (via group-based delivery of didactic content, with 1:1 coaching over a virtual platform). We plan to evaluate whether this innovative virtual group model (VG-Social ABCs) yields similar child and parent gains as seen in the original, longer in-person model. We developed the virtual model in rapid response to the COVID-19 pandemic, and pilot data shows us that this promises to be a powerful way to support families of toddlers with ASD at a developmental stage when they are most amenable to intervention. Beyond COVID-related isolation measures, there continues to be a significant need for increased access to evidence-based early intervention for toddlers with, or at risk for autism, as many families are currently waiting on years-long waitlists for service. Demonstrating the efficacy of this feasible and cost-efficient intervention, will encourage government decision-makers to fund this program for families, leading to increased access to intervention early in life, and improved outcomes for toddlers with ASD and their families. This model will also increase access for families who live in remote and rural regions who often have difficulty accessing important interventions, both within Canada and beyond. ",2021,2024,Holland Bloorview Kids Rehabilitation Hospital (Toronto),450241.54,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Indirect health impacts,2021 +C20498,202111WI2,"Gambling, problem gambling and the COVID-19 pandemic: The experience of LGBTQIA2S+ people",,2021,2023,Université de Sherbrooke,232825.64,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C20499,202111FBD,Supporting the Effective Application of Evidence in Learning Health Systems,"Healthcare organizers across Canada are keen to move from traditional health system setups to learning health systems. Learning health systems collect lessons from everyday care to speed up quality improvement, and to rapidly implement cutting-edge health research into practice (e.g. rapidly studying and optimizing the processes and outcomes of telehealth visits as replacements for in-person clinical visits during COVID-19). By doing so, learning health systems aim to improve patient and provider experiences, improve health outcomes, make systems more fair and equitable, and ensure value for money. Many researchers, health system staff, and policy-makers are working to make learning health systems the norm, but there are still many steps to figure out. One such step is how to apply the lessons learned from systems studying their own processes and outcomes. Who needs to be involved in applying these lessons? How do we get these people together and build processes to apply lessons learned? This study seeks to answer these questions by studying the dynamics of Alberta's community of implementors (people who apply lessons in different parts of the healthcare system) and by interviewing the Implementation Science Collaborative, a large-scale initiative that works to help systems successfully apply lessons learned in Alberta's learning health system. This study will create knowledge around how to coordinate implementors and apply lessons in ways that improve the quality and value of health care. ",2021,2024,University of Alberta,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2021 +C20501,202109PJT,Liberation from mechanical ventilation using Extubation Advisor Decision Support: The multicentre (LEADS) Pilot Trial,"During the pandemic, an increasing number of critically ill patients require life-saving ventilators. Given that ventilators are limited and prolonged exposure to ventilators is associated with patient harm (i.e., infection, weakness), it is vital to rapidly transition patients from ventilators to breathing on their own (i.e., successful extubation). Failed attempts at extubation (i.e., requiring breathing tube reinsertion) are harmful (increase the chance that patients will die), costly (increase the time spent in critical care units), and in COVID-19 patients, threaten the well-being of health care providers. To assist with extubation-decision making, clinicians assess individual patient's readiness to be extubated, by conducting spontaneous breathing trials (SBTs). During SBTs, ventilator support is reduced and clinicians observe patient's breathing pattern to determine if they can breathe on their own. However, SBTs can be performed in several ways and current indices to help clinicians to predict extubation success are poor. Previously, we showed that loss of breathing rate variability (capacity to increase or decrease breathing rate) during an SBT was the best predictor of extubation failure. Based on breathing rate variability, we developed and evaluated the Extubation Advisor (EA) tool. This novel tool aims to reduce the risk of extubation failure for individual patients by combining clinician's assessments of extubation readiness with breathing rate variability to improve outcomes prediction. We aim to conduct a multicenter, pilot randomized trial comparing this tool to standard care. In this trial, we will assess whether we can enroll patients, with and without COVID-19, and implement the protocol as designed. This is the first trial of an extubation decision support tool and specifically, this new technology. The EA tool holds promise as a tool that will aid clinicians to rapidly and safely transition patients from ventilators to breathing independently. ",2021,2023,Unity Health Toronto,359589.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health | Innovation,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +C20502,202109PJT,Application of a Bayesian strategy to ABCD: Identification of substance-use risk and COVID-19 effects on neurodevelopment,"Since use during adolescence is common, however earlier ages of initiation are associated with numerous negative consequences, including increased likelihood of a substance use disorder in later life. Multiple lines of evidence indicate that individual differences in neural development contribute to vulnerabilities for earlier ages of substance use initiation. However, the neural basis of this at the network level is not well understood. The Adolescent Brain and Cognitive Development (ABCD) study provides an unprecedented opportunity for assessment of neural networks of substance-use risk. However, children in this cohort now face a unique developmental challenge: entering adolescence during the COVID-19 pandemic and associated response measures. Here, we propose a novel Bayesian framework to accelerate, enrich and individualize this assessment. In direct response to PAR-19-162 ('Accelerating the Pace of Child Health Research Using Existing Data from the ABCD Study'), our proposal will establish, refine, and deploy Bayesian hierarchical longitudinal modeling tools to carefully quantify deviation from normative development in brain trajectories relevant to substance-use risk in the ABCD dataset with careful consideration of COVID-19 effects. ",2021,2026,McGill University,556002,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20503,202112GSM,"Improving the Public Health Pandemic Response via an Open, Consensus-Driving Genomic Contextual Data Standard","A key to the SARS-CoV-2 pandemic response has been the sequencing and sharing of large amounts of genomic data and associated contextual information. While genomic data (genetic code) is one important part of the response, it is the contextual data that tells us who was infected, where infection probably occurred, what their clinical outcomes were, and what the sampling methodology was. Different regions have created different standards of contextual information collection, often resulting in data sets that are difficult to merge and compare across administrations. We need to see the bigger picture, yet we cannot create it from incompatible pieces. This proposal is for the creation of a community developed data standard that is adaptive to user needs, accessible, and formatted such that it can be readily processed by a computer. This will be accomplished via engagement with genomic domain experts and data structure scientists. Qualitative semi-structured interviews with domain experts will assist in determining relevant contextual data needs and research questions regarding SARS-CoV-2 transmission scenarios. Information scientists will be consulted to help convert this information into a data model, a means of organizing data elements and the relationships between them, before transforming it into computer code. This work will then be formulated into a protocol that will support other researchers to generate and collaborate on their own data standard scenarios. The end result will be an accessible specification data structure that aids in the creation of compatible genomic contextual data sets and enables computational processing of complex research questions, thereby accelerating public health pandemic response time across disparate health jurisdictions. ",2021,2022,Simon Fraser University,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",,2021 +C20504,202109PVV,The SEAMLESS Study: A pragmatic multi-site randomized waitlist-controlled trial of a SmartphonE App-based MindfuLnEss intervention for French- and English-speaking cancer SurvivorS,"The number of cancer survivors in Canada is increasing because of advances in early detection and new treatments. Unfortunately, almost half of all survivors experience long-term negative symptoms and side-effects after treatment such as fatigue, pain, anxiety, distress, and fear of cancer recurrence/progression. These symptoms impair survivors' ability to enjoy a good quality of life, work and give back to their families and society. Thus, cost-effective and safe ways to provide psychosocial care to cancer survivors after treatment are needed. Our team has developed and studied Mindfulness-Based Cancer Recovery (MBCR), a program which trains people to manage symptoms and live life more fully using mindfulness meditation. MBCR has shown positive effects on a broad range of health outcomes in cancer survivors. However, many cannot attend the MBCR program in person for reasons such as living far away from treatment centres, costs of parking, travel and time off work, low immunity, side-effects, scheduling problems, and now COVID-19 precautions. Therefore, to overcome such difficulties our team has developed a low-cost smartphone/mobile app-based version of MBCR which includes teaching in mindfulness and guided meditation exercises. Now, we want to learn whether app-based MBCR is effective in reducing symptoms for a wide range of cancer survivors in real world settings. We will use pragmatic methods to compare a group of patients receiving app-based MBCR for 4 weeks in their own homes, to a waitlist control group on a range of symptoms including stress, fear of cancer recurrence, fatigue, anxiety, depression and physical function. If we are successful in showing the effectiveness of app-based MBCR for cancer survivors, this low-cost app could easily be made available for wider application across Canada and safely reach a large number of patients and survivors to help ease the transition from acute cancer care, without needing to come to a health care facility. ",2021,2022,University of Calgary,79000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20505,202110QA3,Adapting virtual psychological pain care to Francophone workers in primary care physiotherapy for low back pain,"The COVID-19 pandemic has challenged the feasibility of multisession in-person treatment options, creating the need for accessible solutions that are low-cost, low-burden, and remove the need for face-to-face meetings. This has led to the development of single-session, virtual pain interventions that have proven to be efficient at improving mental and physical health in individuals with chronic pain. However, these evidence-based virtual treatments have yet to be adapted to Francophones in primary care, who are generally underrepresented in research and form a language minority in Canada. The purpose of this study is to adapt a virtually delivered psychological pain intervention to Francophone workers in a primary care physiotherapy for low back pain and examine its preliminary effects on disability outcomes. The French version of ""Empowered Relief"", a 2-hour, single-session class designed to reduce pain specific distress will be delivered to francophone workers through a web-based platform. Empowered Relief provides a complementary, low-burden treatment to physiotherapists who have called for additional support to meet the psychological needs of injured workers who are experiencing symptoms of pain. Based on the findings of this study, we will offer recommendations for adapting Empowered Relief in view of a large-scale study of the implementation of virtual psychological pain care in the context of primary care rehabilitation in Québec. ",2021,2022,Université de Sherbrooke,0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20506,202104PJT,"Screen technology, parent-child interactions, and neurocognitive development in early childhood","The first five years of life, especially the preschool years (3-5 years), are a significant period of cognitive development that sets the foundation for life-long social, emotional, and mental health. Recent advances in technology have resulted in the increased use of mobile screen devices (e.g., tablets, smartphones) during early childhood that didn't exist in previous generations. This exposure has intensified with COVID-19. Research has not kept pace with the technological and cultural changes. Therefore, we lack evidence about how young children's engagement with this new technology impacts their cognitive development. Furthermore, it is unclear if parents can moderate effects. Utilizing a sample of preschoolers and their parents, this study will address these substantial evidence gaps by examining: 1) screen time patterns, 2) the association between screen time patterns and cognitive development overtime, 3) the differences in quality of parent-child interactions during three sedentary behaviour tasks (i.e., television viewing, game app, storybook reading), and 4) the influence of parent-child interaction quality on the association between screen time patterns and cognitive development. A total of 360 preschool children at ages 3, 3.5, or 4 years will be recruited and data collection will occur at three time-points over 1 year (baseline, 6 months, 12 months). Screen time patterns (e.g., device, type, content, context) will be measured with an online diary completed by parents daily for 2 weeks. Cognitive development, including memory, impulse control, language, and self-control, will be measured virtually via Zoom. The quality of parent-child interactions will be determined by observing three tasks (i.e., television show, game app, storybook reading) virtually via Zoom. The novel findings from this study will help to inform guideline updates, health promotion initiatives, and future interventions targeting healthy development in our youngest Canadians. ",2021,2025,University of Alberta,344480.29,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20507,202112GSM,Longitudinal analysis of the viral evolution and neutralization assays of the pathogenic coronaviruses in VERO cells.,"The coronavirus family encompasses three pathogenic coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV), which have the capability of infecting humans causing cytokine storms, acute respiratory distress syndrome, permanent lung damage, and persistent infection can be fatal. The pathogenic coronaviruses have pandemic potential with the epidemic of SARS-CoV-1 in 2002 and MERS-CoV in 2014. In addition, the emergence of SARS-CoV-2, the etiological agent of COVID-19 pandemic has infected more than 260 million people, and caused more than 5 million deaths, as of late November 2021. Besides, the COVID-19 pandemic has illustrated the capacity of coronaviruses as highly transmissible pathogens leading to severe strains on the health care system and impact on global socio-economic activities. The appearance of multiple variants over the past months gaining resistance against the immune response of vaccinated individuals has highlighted the rapidity of the evolution of coronaviruses. Therefore, to study the viral evolution of these pathogens, we produced a longitudinal study of infecting VERO cells with SARS-CoV-1, SARS-CoV-2, and MERS-CoV during 8-months and harvested the supernatant and cell isolates for whole-genome sequencing. The sequencing results at different time points will demonstrate the mutations gained during the passaging of the viruses from humans to non-human primate cell lines indicating variable regions in the genome allowing adaptability. Also, the sequencing of cell isolates and supernatant will allow us to compare the genetic variant found inside the cells versus viruses that are transmitted. Thus, our analyses could confer a better understanding of the viral quasispecies, genetic evolution, and zoonotic transmission of the pathogenic coronaviruses. ",2021,2022,University of Ottawa,13825,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C20508,202108VCF,COVID-19 and Vaccine Trust in Black Communities: State of Play and Education and Engagement Programs,,2021,2023,University of Ottawa,158000,Human Populations,Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20509,202111FBD,Primary Prevention of Cancers-Related to Tobacco and Alcohol Use in Gender Minority Communities Across Canada,"About 50% of cancer diagnoses are preventable by adopting healthy lifestyle behaviours such as limiting the consumption of alcohol and tobacco. World-renowned cancer research organizations have reported that there is no safe level of alcohol consumption or cigarette smoking that does not increase the risk of developing cancer. Gender minority (GM) people- people that have a gender identity that is different from their sex assigned at birth such as transgender men or transgender women- have a higher risk of developing cancer because studies outside of Canada have demonstrated that this community has higher rates of substance use. Data on Canadian GMs is limited as many surveys do not include a question that asks participants about their gender identity. In my research, I will be using two Canadian datasets that have recently collected information regarding the gender identity of their participants, and I will use this information to explore the rates of alcohol consumption, tobacco use and related-cancers in GM people. I will also use this data to determine how the rates of alcohol consumption and tobacco use has changed in GM communities since the COVID-19 pandemic. I will help explain the results of this data by learning from GM people themselves, through the use of focus groups. This research will uncover the rates of alcohol and tobacco use in the Canadian GM community and help researchers understand what factors contribute to the use of these two substances in this community for policy development. ",2021,2024,University of British Columbia,82950,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20510,202104PJT,The health implications of the loss of a loved one during a pandemic: grief trajectories and the biopsychosocial-spiritual health implications of the circumstances of death and restrictions on support for dying and funeral rituals,,2021,2024,Université du Québec à Chicoutimi,151087.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20511,202112GSM,Impact of Covid-19 on mental health disparities in ethnic minorities,"Research indicates that Covid-19 pandemic has intensified the health inequities that ethnic minorities experience. However, little research has been done in Canada. This study will build upon current literature to identify mental health disparity in visible minorities of Canada using longitudinal survey from Canadian Perspective Survey Series (CPSS). This study will then examine the association between ethnic minority status and behavioral factors associated with mental health disparities. Further, this study will explore whether self-reported mental health outcomes are reflected in the actual use of mental health services and treatment using health administrative data from Immigration, Refugees, and Citizenship Canada (IRCC), Vital statistics, physician claims, and hospital discharge records. Mixed-effects regression analysis will be conducted to examine the direct associations between ethnicity, immigration status and reported mental health outcomes. Analysis will also examine the association between ethnicity and utilization of adequate mental health care services during Covid-19 pandemic. The findings will help to inform policy makers to identify potential barriers to accessing mental health services and to mobilize resources to the populations in need. ",2021,2022,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20512,202112GSM,Identifying the effects of COVID-19 on the mental health of the visible minority essential workers and their coping strategies,,2021,2022,University of Calgary,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20513,202104PNN,At-home Breast Oncology care Delivered with E-Health solutions - The ABODE Study,"The COVID-19 pandemic has significantly impacted healthcare service delivery, highlighting the need for high quality virtual patient care. We have developed a multi-dimensional remote patient eHealth solution for newly diagnosed breast cancer patients and their practitioners to use during the diagnostic and surgical follow-up period. We have developed the Breast Cancer Treatment Application (BCTA) that can facilitate virtual consultations, deliver patient education material, and collect patient reported outcome measures. Using a randomized controlled trial design across three sites, we will evaluate a variety of outcomes for breast cancer patients who will use the BCTA through their diagnosis and treatment. Our study will compare changes in patient activation over 1 year among newly diagnosed breast cancer patients between those using the BCTA and those receiving standard care. We will also evaluate anxiety, psychosocial well-being and quality of life between the two groups. To further understand the impact of the BCTA, we will assess the health services utilization and patient satisfaction outcomes. Our innovation will provide a solution to improve communication between patients and their healthcare providers. ",2021,2022,University Health Network,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20514,202110OLG,Addressing the Shortage of Professional Resources in OLMCs: Strengthening Recruitment and Retention Strategies for the Benefit of New Brunswick's Francophone and Acadian Communities,"Google translate: At home and abroad, COVID-19 has exposed already well-felt human resource gaps in health systems. The supply of health services and care in New Brunswick is weakened by a shortage of registered nurses and doctors, which particularly affects rural areas, where official language minority communities (OLMCs) are concentrated. Since 2008, the Vitalité Health Network (Network), whose operating language is French, serves OLMCs in four geographic areas. However, a hundred positions for doctors and approximately two hundred positions for registered nurses are to be filled in the territory administered by the Network. Faced with this reality, combined with the current health crisis, it is imperative to strengthen the Network's recruitment and retention strategies to ensure its viability and maintain services and health care that meet the needs of OLMCs. In a dynamic of co-creation of knowledge, we have thus established a partnership with the Network. The results of this study will enable our partner to identify and implement concrete solutions that emanate from its context in order to increase the recruitment rate and promote the retention of professionals in post. By taking stock of the vacancies and examining the turnover rate, it will be possible, on the one hand, to determine whether the greatest challenges are in terms of recruitment or retention. On the other hand, it will be a question of examining the factors which make attractive the internal environments, such as the working conditions, and the external (or community), such as the living environment of the professionals. The methodology is based on a mixed estimate that combines quantitative and qualitative approaches.]",2021,2022,Université de Moncton (New Brunswick),76912.03,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C20515,202112GSM,Impacts of COVID-19 on Emergency Department service delivery for people who use opioids: Royal Alexandra Hospital and Peter Lougheed Centre service utilization trends and patient perspectives,,2021,2022,University of Alberta,13825,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20516,202110LGL,"Meet us where we're at: Understanding needs, preferences and acceptability of sexual and reproductive health testing, contraceptives and counselling outside of traditional clinical settings","2SLGBTQQIA+ people in Canada have unique needs and experience barriers within sexual and reproductive health care (SRHC), where many providers have little knowledge of our experiences, bodies, or sexual and reproductive health needs. During COVID-19, access to traditional in-person clinical care shifted dramatically. For 2SLGBTQQIA+ communities the pandemic exacerbated issues in access, while also introducing new options like virtual care. Access to in-person health services was reduced, there were greater challenges in accessing fertility clinics, abortion services, and surgical procedures, including gender affirming surgeries (considered non-urgent by the health system). At the same time, health care providers in many provincial contexts began providing virtual care, such as STBBI testing, HIV care and pre-exposure prophylaxis (PrEP) appointments. Led by the Community-Based Research Centre (CBRC), in collaboration with our project partners, we seek to identify 2SLGBTQQIA+ community needs, preferences, and acceptability of SRHC outside of traditional clinical settings, with a focus on community members who face intersecting forms of oppression; to understand the experiences, challenges and learnings of SRHC providers in non-traditional clinical care settings; and identify recommendations for policy and practice changes. Utilizing a community-based research approach, informed by decolonization, intersectionality and sex and gender based analysis (SGBA+), research activities are (a) secondary analysis of survey that CBRC have collected through its national 2SLGBTQQIA+ COVID-19 study; (b) English & French qualitative interviews with SRHC providers who support 2SLGBTQQIA+ communities; (c) English & French qualitative focus groups with 2SLGBTQQIA+ community members who have accessed SRHC; (d) development of resources to support the implementation of community-oriented approaches to proiding SRHC to 2SLGBTQQIA+ communities. ",2021,2022,University of Victoria,158000,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2021 +C20517,202109PJT,Multiple social tie transitions and their impact on cardiometabolic risk factors in aging women and men (MORE),"Social connectedness is important for promoting healthy aging among Canadians. In particular, measures of social connectedness such as marital status are linked to greater survival and less chronic disease. Although the COVID-19 pandemic has really highlighted the importance of social ties, older people are especially at high risk of transitioning from multiple to few or no social ties, and this can threaten health differently in women versus men. However, there is very little research examining whether and how changes in different social ties influence the biological indicators of aging, or how their effects vary for women and men. Our preliminary work suggests that marital status, social participation, social networks and living arrangement are more strongly linked to linked to obesity and hypertension in women than men in Canada. Far less is known about whether economic circumstances alter the importance of social connectedness for cardiovascular risk. To fill these critical knowledge gaps, the current project will build on our initial work to (1) assess changes in obesity and hypertension over time in women and men by types of social tie transitions; (2) quantify how changes in different social ties impact these healthy aging indicators; and (3) explore the role of financial autonomy in social connectedness and cardiovascular risk. Using established techniques, we take a unique approach of looking at sex/gender, which is typically given less attention in cardiovascular research. The results will have implications for decision-makers who shape tailored, evidence-driven policies, services and programs that promote social connections and engagement among Canadians in order to advance our national healthy aging strategy. ",2021,2024,University of British Columbia,181305,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20518,202104GA7,What impacts COVID-19 vaccine uptake in Métis Citizens in Ontario? A population-based data linkage study.,,2021,2022,University of Waterloo,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +C20519,202109AI2,"Evaluating the Benefits of Rapid Access Addiction Medicine Clinics for Problematic Alcohol Use: A Retrospective Cohort Study to Inform Policy, Practice, and Future Research","Alcohol use in Canada, and globally, is a leading risk factor for disease, disability, and death. The COVID-19 global pandemic has also led to an increase in alcohol consumption amongst Canadians, with higher rates in individuals struggling with both mental health and substance use problems. The importance of access to care for problematic alcohol use (PAU) is at an all-time high. Treatment for PAU can be difficult to access, as there can be lengthy wait times for services, and care remains fragmented. In many cases, persons with PAU present themselves to be seen at emergency departments (ED) due to gaps in care, resulting in high use of the health care system. Rapid Access Addiction Medicine (RAAM) clinics have been implemented in recent years to provide easy access to evidence-based care for people with substance use problems so they can get the care they need, with the vital goal of improving their outcomes. RAAM clinics have opened in many regions within Canada to help individuals with PAU, however there remains a need to conduct analyses of their available data to evaluate the benefits they offer to people living in Canada and the healthcare system. It is also important to assess whether RAAM clinics provide sufficient value for the funding invested in their set-up and operation. In the proposed research, we will use statistical methods and anonymized health data to assess whether RAAM clinics have helped improve the outcomes of individuals with PAU, and whether they provide good value for money. Our research team consists of people with lived expertise as well as experts in research methods, addiction medicine, mental health, public health, and health services research. We have partnered with members of key organizations that can impact policy and practice regarding PAU here in Canada. ",2021,2022,University of Ottawa Institute of Mental Health Research,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20521,202104PNN,Starting before birth: Preventing maternal mental health problems via a virtual and partner-inclusive intervention,"Postpartum depression is one of the most common complications of pregnancy. About 15% of new mothers have clinically severe levels of depressive symptoms and about 20% have mild to moderate symptoms. Over 300 studies and 15 meta-analyses have documented short- and long-term effects of postpartum depression on both mother and child. In Canada, since the start of the COVID-19 pandemic in March 2020, pregnant women have reported levels of depression 2-3 times higher than pre-pandemic levels. We are facing an unprecedented need for psychological support for an already vulnerable population. Accordingly, we have adapted an evidence-based program for the prevention of perinatal depression to a virtual and partner-inclusive format appropriate for social distancing. Our objective is to test the efficacy of the virtual Parents & Babies intervention, a prevention program based on workbook and/or online exercises as well as weekly telephone calls. The program begins in pregnancy and continues until the first 3 months after the baby's birth. We will enrol 640 women for whom an intervention is indicated; i.e. those presenting symptoms of depression in early pregnancy. Our program recognizes the importance of partner support for maternal mental health, and partner participation is encouraged. Our multidisciplinary team includes researchers/clinicians from public health, psychiatry, psychology, obstetrics, nursing, and economics, with extensive clinical expertise in perinatal mental health and child development. We have already completed a pilot study. The clinical team and research infrastructure are ready and in place. Virtual, or remote, care is a promising solution to longstanding barriers to treatment. If effective, the intervention offered at a critical period in maternal, fetal and infant development and during a stressful pandemic period, could become a population-based health promotion tool for Canadian families and implemented elsewhere in the world. ",2021,2022,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",0,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20522,202112GSM,When the virtual interferes with the real,"Google translate: This research project aims to explore the effect of a type of social network (Instagram) on body image disturbances in populations with dysfunctional eating attitudes and behaviors (ACAD). The relevance of the development of this project lies in the observation of an increase in the problematic use of the internet and social networks in times of COVID-19 and its impacts on the mental health of users (Fernandes, 2020). Content shared on the mass media, often demonstrating unrealistic ideals of beauty, would be a factor causing an increase in the prevalence of individuals with a negative body image and would increase the desire to achieve a certain type of body idealized by the society (Lwin & Malik, 2012). Indeed, social media, such as Instagram, is often perceived as a risk factor, because it is oriented towards comments on physical appearance, which has the effect of increasing body dissatisfaction (Griffiths et al. ., 2018?; Sidanie et al., 2016?; Tiggeman and Barbato, 2018).In this study, this link between social media use and body image disturbances will be investigated in a population with ACAD, the latter being more likely to develop an eating disorder (ED). Indeed, ACADs have significant individual and psychological consequences and are recognized as precursors to EDs (Labossière, 2019; Turgeon et al, 2015). To date, only a few empirical studies have documented the influence of social media on body image disturbances, and none, to our knowledge, has documented this link in a population with ACAD.]",2021,2022,Université du Québec à Trois-Rivières,13825,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20523,202112GSM,"A Remotely-Delivered, Combined Exercise Training Program for Mental Health in Breast Cancer Survivors: A Pilot Study","Background: Breast cancer survivors (BCS) may experience poor mental health following chemotherapy treatment. The COVID-19 pandemic has exacerbated these symptoms leading to increased levels of anxiety and depression in BCS. Physical activity (PA) can lead to improvements in mental health and quality of life among BCS. Home-based PA interventions may be useful for improving mental health in BCS while adhering to physical distancing guidelines during the COVID-19 pandemic. Objectives: This study will pilot a 12-week, home-based combined exercise (aerobic + resistance training) versus stretching/toning (active control) intervention on mental health outcomes (i.e., depression, anxiety and negative affect) in BCS. It is hypothesized that BCS receiving the combined exercise intervention will experience significant improvements in their mental health compared to the active control group. Methods: The combined exercise group will participate in a live 60-minute instructor-led aerobic and resistance exercise session 3 days per week via videoconferencing (i.e., Zoom). The active control group will participate in a live instructor-led stretching program 3 days per week via videoconferencing (i.e., Zoom). Mental health will be measured through self-reported questionnaires assessing anxiety, depression, and negative affect administered at baseline and post-intervention (i.e., 12 weeks). Semi-structured interviews will be conducted post-intervention to assess their experience with a home-based exercise program. Significance: This study will provide evidence for the feasibility of a home-based exercise intervention that can be used to manage mental health in BCS following chemotherapy treatment. ",2021,2022,University of Toronto,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20524,202112GSM,Methodological considerations for studies of preterm birth or small-for-gestational-age birth after vaccination during pregnancy: A case study on COVID-19 vaccine.,,2021,2022,University of Ottawa,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Adverse events associated with immunization,2021 +C20525,202112GSM,Longitudinal Mental Health Symptom Changes Prior to and During COVID-19 Among At-Risk Populations,,2021,2022,McGill University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20526,202111FBD,Developing and measuring practice-based quality indicators of physicians in nursing homes,"The COVID-19 pandemic shows the threat to older adults, especially residents living in nursing homes. Residents living in nursing homes are impacted by the care practices delivered by their physicians in these homes. Care practices of physicians includes all admission and annual assessments, monitoring and disease management as health changes, routine medical care, and medication management. Little is known about the quality of the practice delivered by physicians and this needs to be measured. Physicians themselves do not believe that pre-existing measures reflect physician quality, as they often reflect the resident-level outcomes instead. By measuring practice-based quality indicators, this research will evaluate the quality of practice delivered, assess the role of physicians, identify performance gaps, and direct quality improvement initiatives. The aims of my doctoral research are to (a) measure the quality of practice of physicians in nursing homes based on accepted standards and (b) examine the associations between the quality indicators and resident-important outcomes such as the use of antipsychotics, transfer to the emergency department, admission to hospital, and death. This research will uniquely use electronic medical record (PointClickCare) data from 120 nursing homes, which includes resident information. This data repository is the first of its kind in Canada and is a new way of using electronic medical record data to measure quality. The findings of this research will be used to give individual physicians feedback on their performance, set benchmarks for sector-wide performance, and create a tool to monitor and track physician quality of practice. Further, this research will inform policy with recommendations on how to best use health resources in nursing homes including implications for publicly funded care. ",2021,2024,McMaster University,82950,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2021 +C20527,202112GSM,Youth exposure to marketing of sugary beverages and intake across six countries during pre- mid- and late COVID-19 pandemic,"Unhealthy food marketing is omnipresent and influences youths food preferences, consumption patterns and purchases, with important implications for health later in life. Marketing of sugary drinks is of particular interest as these are a principal source of sugar in young Canadians diets and intake is associated with obesity. Globally, public health policies have been implemented to restrict marketing directed at youth. In parallel, exposure to marketing of sugary drinks may have increased as a result of greater screen time during COVID-19 lockdowns and preliminary evidence suggests sugary drink intakes increased among youth. This project will explore youth exposure to marketing of sugary drinks across 6 countries and the relationship between marketing exposure and sugary drink intake during 3 phases of the COVID-19 pandemic (pre, mid, late). Exposure to marketing in various locations and intake of sugary drinks will be measured in repeated surveys of 11,500 youth ages 10-17 from Canada, Australia, Chile, Mexico, United Kingdom and United States at each phase of the pandemic as part of the International Food Policy Study. The level of lockdown restrictions will be assessed at each time point in each country to investigate associations with marketing exposure and sugary drink intake. Differences in potentially vulnerable subpopulations will be explored. This research uniquely provides in-depth individual-level marketing exposure data at various time points of the pandemic. Findings will contribute to global knowledge on the impact of food marketing on health-related outcomes among youth to inform food marketing policy, and may also inform future health crises, ensuring public health measures are supported by efforts to protect vulnerable populations. ",2021,2022,Université Laval,13825,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20528,202110OLG,"Mental health, risky behaviors and access to support services: the experience of postsecondary students from OLMCs in Manitoba and New Brunswick","Google translate: Young adults in post-secondary settings are going through a major life transition; many are likely to develop mental health problems, risky behaviors and experience academic difficulties. The COVID-19 pandemic has exacerbated the challenges of forming a social network, negatively impacting their mental health. Young people do not often use professional support services due to a lack of awareness of the availability of services and barriers to access. Through an online survey, this study aims to describe the experience of the undergraduate student population of two French-speaking Canadian universities in official language minority communities (OLMCs) (Université de Saint-Boniface et de Moncton) regarding mental health and access to psychosocial support services, substance use, road safety, violence, sexual practices and addiction to personal electronic devices. The data will be analyzed according to age, gender, ethnolinguistic identity profile (first and second language Francophones; international Francophones) and site (rural/urban context and density of Francophones), as these factors may influence health and well-being. Group interviews will be used to disseminate and validate the results of the survey among the student population and to identify the obstacles faced by these young people with regard to access to support services on campus and in the community in the official language. of their choice. The data collected will support the formulation of recommendations on how to promote their access to available support services. These recommendations will be shared with collaborators and political decision-makers in order to support the development of these young people, who are essential to maintaining the vitality of OLMCs.]",2021,2022,University of Manitoba,47632.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20529,202112GSM,"Understanding the social, mental, and health impacts of COVID-19 in Canada: Leveraging and extending data from the iCARE Study",,2021,2022,Université du Québec à Montréal,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2021 +C20530,202110MFE,Effectiveness of a Transdiagnostic Mobile App Intervention for Mental Health Concerns in University Students: Randomized Controlled Trial,"University students often present with mental health concerns that impact a student's ability to function academically, socialize, and are a cause of substantial suffering for students in terms of anxiety, depression, and other mental health issues. Despite a large percentage of students presenting with high levels of depression and anxiety symptoms many of these students have not received treatment. This may be due to several reasons such as not meeting a diagnostic criteria required to access services, accessibility issues, high cost of services, and a lack of availability. However, treatment trials aimed at treating broad spectrum mental health concerns that these students present with are rare. Transdiagnostic psychotherapy is one potential treatment for these broad mental health concerns as it can address several mental health issues within one treatment. Utilizing the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in an online group therapy in conjunction with a mobile app affords the opportunity to treat a broad spectrum of mental health issues in these young people. This treatment also allows these students to connect with other students during this period of increasing isolation from the comfort of their homes due to the COVID-19 pandemic, eliminating accessibility/availability issues. In addition, there is also a lack of information regarding mental health outcomes and treatment utilization among this highly vulnerable group of students, which may inform health policy and service delivery. The proposed study will address gaps in knowledge and gaps between evidence and practice to improve overall quality of and access to care for university students with mental health concerns. The work will be broadly generalizable and has the capacity to improve health system functioning and population health. ",2021,2024,University of Calgary,106650,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20531,202104PJT,"Perioperative Anticoagulant Use for Surgery Evaluation -Virtual Visit (PAUSE-Virtual), a simple perioperative anticoagulant management approach, replacing a resource-intensive in-person doctor-patient consultation, with a simple virtual care model that will provide a new standard of care for patients on a Direct Oral Anticoagulant or warfarin and require elective surgery/procedure.","The purpose of the PAUSE-Virtual Study is to show that by changing pre-surgery visits with patients taking a blood thinner (direct oral anticoagulant (apixaban, dabigatran, edoxaban, rivaroxaban or warfarin) when they require elective surgery, using a standard, in-person proven approach, to a virtual visit, either telephone or video conference, is as safe. Patients who are receiving a blood thinner for the medical condition known as atrial fibrillation (AF) and require an elective surgery/procedure, is common. These patients have to stop taking their blood thinner for a certain time before the procedure to reduce serious complications of stroke or bleeding. For doctors who help manage these patients before a procedure, appointments have been traditionally done in-person. Patients receive instructions about when to stop and restart their blood thinners and taught how to self-administrator a short acting blood thinner (heparin) if needed. The COVID pandemic changed the way these appointments were done, making it important to contact these patients without them having to come to the hospital for an in-person visit. Virtual patient care, by telephone or video conference, to communicate to patients about when to start and restart their blood thinner was necessary. This study wants to show that this virtual method of instruction, using a standardized plan of managing patient care, is easy, acceptable to patients and as safe when compared to an in-person meeting. Such instruction would also be cost-efficient standard post-pandemic. Prior work has shown us that both a standard care of patients who are receiving blood thinners and a point-of-care decision ""app"", available through Thrombosis Canada (www.thrombosiscanada.ca) website, has been trusted by hematologist's during this virtual visit successfully. We will show, by following up at 30 days, that this standardized management plan is safe and can be done virtually, with a low risk of stroke and major bleeding. ",2021,2024,McMaster University,559024.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20532,202109PP1,Vaccination hesitancy: Understand to act better,"Google translate: Vaccination is a very effective public health measure to prevent disease. However, more and more people have major fears and doubts about vaccines. It is estimated that one person in three would hesitate to be vaccinated or to have their child vaccinated. This phenomenon is called ""vaccination hesitancy"". Hesitant people may refuse certain vaccines or delay vaccination, and these behaviors have been linked to outbreaks of vaccine-preventable diseases, such as measles. This is of particular concern in the context of vaccination against COVID-19, as vaccine hesitancy could negatively affect the success of the vaccination campaign. This program therefore aims to better understand why people are reluctant to get vaccinated or to have their child(ren) vaccinated, as well as to examine why some health professionals are reluctant to vaccinate. In addition, work will be carried out to develop and evaluate solutions to reduce fears and doubts about vaccination and promote informed vaccination decisions. Various qualitative (interviews, ethnographic research) and quantitative (surveys) research projects will be carried out to do this.]",2021,2027,Université Laval,137665.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +C20533,202112GSM,Investigating the potential effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) vaccination on modulation of the latent human immunodeficiency virus (HIV) reservoir,"Antiretroviral therapies have transformed HIV from a life-threatening infection to a manageable health condition, but these drugs must be taken for life. This is because HIV establishes a latent reservoir of infected cells by integrating its DNA into the DNA of infected host cells. Antiretroviral drugs cannot eliminate cells harboring latent HIV, nor can the immune system. A theoretical strategy to cure HIV, dubbed ;kick-and-kill, aims to wake up reservoir cells by applying a strong stimulant, while boosting the immune system's ability to eliminate these infected cells. To further develop this strategy, we need to better understand what types of stimulants can safely and effectively modulate the HIV reservoir. The recent mass rollout of novel mRNA vaccines against COVID-19 gives us a unique opportunity to do so. We already know that standard vaccines (e.g. against influenza) induce generalized immune responses that can transiently stimulate HIV gene transcription. Because the novel mRNA vaccine technologies used for COVID-19 stimulate particularly strong immune responses, these may modulate the HIV reservoir more strongly. My thesis will explore the potential effects of COVID-19 mRNA vaccination on the reservoirs of 62 people with HIV on ART for whom we have collected blood samples pre-vaccination, and at various times after the first, second and booster shots, along with sociodemographic and clinical data. I will quantify HIV mRNA transcription, reservoir size, plasma cytokine levels and T-cell activation profiles before and after vaccination, and explore the magnitude of these changes with sex, age, clinical HIV parameters, and vaccine-induced antibody responses. This study will advance HIV reservoir biology towards the ultimate goal of developing an HIV cure. ",2021,2022,Simon Fraser University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C20534,202110LGL,Fostering Dialogue Across Care Worker and 2SLGBTQI Older Adult Divides: An Arts-Based Action Research Project,"Two-spirit, lesbian, gay, bisexual, trans, queer and intersex (2SLGBTQI) older adults face increased barriers to accessing healthcare services. These barriers include Canadian healthcare systems and structures that continue to be geared towards a cis-heteronormative patient population (Daley, 2006; Mule et al., 2009) as well as discrimination and negative care encounters that older 2SLGBTQI people have faced earlier in life (e.g, Brotman et al., 2007). Fears of homophobia and transphobia in home care and long-term care and having to ""go back into the closet"" are especially widespread. These are fears documented by researchers for over a decade (e.g., Brotman et al. 2007; Sussman et al., 2018); fears which, significantly, can target care workers who are mostly people of colour and immigrants (Pang, forthcoming). As the COVID-19 pandemic has shown care workers perform ""essential"" work, yet are undervalued, and can experience violence in the workplace (Daly et al., 2011). While they seek to provide person-centered care and to access opportunities to better understand 2SLGBTQI clients' needs, these opportunities are lacking (Daley and MacDonnell, 2015). This research study seeks to better understand the key disconnects between 2SLGBTQI older adults and care workers in the personal support work sector, and to identify how these can be bridged through arts-based action research. Arts-based methods are an increasingly popular research approach (Luttrell & Chalfen, 2010; Mitchell, De Lange, & Moletsane, 2017) where art plays a primary role in knowledge co-creation and is a source of data representation (Kunt, 2020). An arts-based method will allow researchers to explore sensitive and possibly controversial topics and issues sometimes difficult to articulate using words alone (Dew, Smith, Collings, & Savage, 2018), ideal for this research that centrally seeks to create space for dialogue, bridge gaps, and improve access to care. ",2021,2022,Direct Payment,133506.84,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Sexual and gender minorities,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2021 +C20535,202109PJT,Mixed-methods study investigating the efficacy and acceptance of a seated exercise program delivered virtually to improve mobility in older adults living with stroke,"BACKGROUND: Stroke is common with a 1 in 4 lifetime risk of stroke after age 25. One of the most sought after goals by people with stroke is improved mobility. Since the COVID-19 pandemic, many hospital programs reduced their capacity while community programs for stroke remain closed. There has been an enormous increase of physical therapists supervising exercise programs in the homes of patients over the internet despite little supporting evidence. People with stroke have substantial physical impairments, and falls can easily occur when balance is challenged. We are proposing a unique seated exercise program that will be safe to deliver over the internet and will improve mobility after stroke. PURPOSE: This will be the first study to evaluate the effect of a seated exercise program delivered by videoconference over the internet to improve mobility after a stroke. In addition, we will explore the acceptance of the program through interviews. METHODS: Older adults who have lived with a stroke more than 12 months and have mobility problems will be assigned to a Seated Exercise Group or a Memory Training Group. Both will be delivered by videoconference over 36 sessions in 12 weeks. Both groups will be measured at 3 time points (baseline), after the treatment (12 weeks later) and follow-up (12 weeks after program ends). We will compare the improvements between the Seated Exercise Group and Control Group on outcomes including mobility, balance, blood pressure and quality of life. We will also examine the costs of the program. We will also interview participants, caregivers and therapists on their experiences with the Seated Exercise Program. SIGNIFICANCE: The Seated Exercise Program delivered through the internet has the potential to provide a safe home treatment to improve mobility for people living with stroke. This program can reach people in more rural locations, eliminate transportation needs and prevent the risk of spreading COVID-19. ",2021,2026,University of British Columbia,486501.75,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Disabled persons | Individuals with multimorbidity,Caregivers | Other,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20536,202104PJT,Influence of the COVID-19 pandemic on chronic disease management among First Nations people in Alberta,,2021,2024,University of Alberta,332392.5,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People | Minority communities unspecified | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20537,202102HI0,Evidence synthesis and knowledge mobilization to advance 'Health in All Policies' in Canada,"Good health has more to do with the circumstances in which we live, work, grow, and play than with factors commonly linked with health, such as healthcare services or a nutritious diet. Addressing these factors and their influence on health outcomes requires an approach to health policy that works across sectors beyond 'health'. The COVID-19 pandemic has amplified differences in social, economic conditions, and illustrates how addressing these differences requires a whole-of-society and whole-of-government response Health in All Policies (HiAP) is one such approach, where different government sectors work together around health. The Intersectoral Partnerships and Initiatives team (IPI) within the Public Health Agency of Canada(PHAC) is looking to benefit from research about how best to take up key lessons from HiAP into its work. Addressing this challenge will strategically inform IPI's current and future partnerships, and support its efforts to improve the circumstances in which we live, work, grow, and play the most effective ways possible. Using data and evidence available on HIAP, the project will develop evidence-based tools and materials for the Intersectoral Partnerships and Initiatives team to use in facilitating more effective collaboration and more strategic partnerships with non-health sector government departments. The project will also mobilize learnings within government and across sectors; both directly (i.e., through presentations to different public health and allied audiences about the review and its findings), and indirectly (i.e., through adopting and encouraging the use of my findings and tools in my day-to-day work as an HSI fellow and policy analyst on the IPI team). ",2021,2022,University of Calgary,27650,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Health leadership and governance,2021 +C20538,202111FBD,Investigating and harnessing the immunoregulatory function of interferons in viral-induced immunopathology,"In response to viral infections, immune activation and inflammation must be tightly regulated as too little will impair clearance of an infection, however excessive immune activation can cause irreparable tissue damage and hinder disease tolerance. In the absence of a suitable vaccine, we must be able to effectively treat severe infections, however, our ability to treat viral-induced immunopathology remains poor. Key to regulating our damaging immune responses to all viral infections are our type I and III interferon responses. Attempts to harness type I interferons in the past have been severely limited by the timeliness required for effective type I interferon therapy. In contrast, while the immunoregulatory type III IFNs are poorly defined, growing evidence suggests their high flexibility as a therapeutic avenue, and their potent ability to suppress unwanted immune responses. Both Ebola virus outbreaks and the COVID-19 pandemic have shown that the ability to produce potent interferon response correlates with improved viral clearance and reduced inflammation and disease severity, and demographics more likely to experience severe infections, such as the elderly, have also been demonstrated to elicit a weaker interferon response during infection. Thus, the potential for interferons to be harnessed as a therapeutic due to their immunoregulatory capacities remains highly promising, yet unexploited. In this project, we will be investigating the mechanisms through how type III interferons are able to suppress viral-induced immunopathology and assess how they can be used safely in a therapeutic capacity. We will also investigate the role interferons may play in determining disease susceptibility in aging populations. By understanding the full type III interferons play in regulating disease tolerance, can develop novel therapeutics, that would be applicable to any viral infection, and would prepare us for any current and future epidemic. ",2021,2024,McMaster University,82950,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2021 +C20539,202104PJT,Annexin A5 as a treatment for COVID-19,"Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a novel coronavirus, SARS-CoV-2. The virus enters the host airway epithelial cells through its spike protein interaction with the host cell receptor angiotensin converting enzyme 2 (ACE2). In severe cases, the disease is complicated by acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ failure, including the lungs, heart, and kidneys. While vaccines have been shown to be effective in reducing the number of cases with COVID-19, the disease is not likely to be eliminated due to the emergence of SARS-CoV-2 variants that may evade immunity to the vaccines or previous infection. It is therefore vital to develop new and effective therapies. Annexin A5 (Anx5) is a human endogenous protein with potent anti-inflammatory, anti-apoptotic and anti-coagulant properties. Our preliminary data show that Anx5 inhibits SARS-CoV-2 spike protein interactions with ACE2 and reduces cellular infection. The proposed research will examine the effects of recombinant human Anx5 on viral infection, inflammation, pulmonary and cardiovascular injuries induced by wildtype (WT) and variant SARS-CoV-2 in hamsters with and without hypertension, and tease out the precise structural basis for Anx5-mediated inhibition of Spike protein binding to ACE2. The proposed research will develop a novel clinically relevant hamster model and life-saving treatment for COVID-19. ",2021,2026,Western University,670828.5,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis | Pre-clinical studies",2021 +C20540,202104PUU,SARS-CoV-2 Spike conformation: impact on Fc-mediated effector functions,"The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causative agent of the ongoing Coronavirus disease (COVID-19) pandemic, is highly contagious and has infected more than 125 million people worldwide and caused over 2.75 million deaths since its discovery. The type, dynamics and persistence of protective immune responses in individuals infected with SARS-CoV-2 is currently under scrupulous investigation. The viral target of this response is the highly immunogenic trimeric Spike (S) glycoprotein, which facilitates SARS-CoV-2 entry into host cells. The antiviral activities of SARS-CoV-2-specific antibodies goes beyond their neutralizing activities and include Fc-mediated effector functions. Unfortunately, these antibody functions remain relatively understudied compared to their neutralizing activities. Why is it important to better understand Fc-mediated effector functions? The main reason is that they represent attractive targets for therapeutic interventions and vaccine development. The work proposed here will provide a better understanding of the S glycoprotein conformation and its impact in Fc-mediated effector functions. Improved knowledge of these responses will be critical to expand our current understanding of the conformational landscape of the S glycoprotein and thus has the potential to identify new vulnerabilities that could be exploited therapeutically. ",2021,2026,Centre hospitalier de l'Université de Montréal (CHUM),592500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C20541,202109AI6,The epidemiology of harmful alcohol use and associated liver-related outcomes among adolescents and young adults in Ontario,"Alcohol is the most common psychoactive substance used by Canadians and causes substantial harm and healthcare costs. Over the past decade in Canada, adolescents and young adults (AYAs: aged 13-39 years) have been shown to be disproportionally affected by alcohol misuse. Of particular concern, studies show that young adults are being more often diagnosed with alcohol-associated cirrhosis than in the past. Identification of at risk AYAs and developing interventions focused on alcohol abstinence and management of alcohol-related complications is necessary to reduce current and future disease burden. To do this, a clear understanding of the epidemiology, geographic distribution, and characteristics of the population at risk are needed along with the appreciation of sex-specific differences and the influence of social determinants of health (SDOH), changes in governmental alcohol policy, and the COVID-19 pandemic. Our overarching goal is to provide population-level data necessary to develop a framework for alcohol-related policy change and inventions specifically targeting AYAs in Canada. This project will use population-level administrative healthcare data from Ontario to describe the epidemiology of harmful alcohol consumption among AYAs between 2000-2021 and how changes in governmental alcohol policy and the COVID-19 pandemic have impacted harm in this group. We will also evaluate how sex-specific differences contribute to the development of liver-related complications in AYAs with alcoholic hepatitis. Finally, we will identify groups of AYAs based on their patterns of healthcare utilization to inform the development of interventions. Our team brings expertise in hepatology, epidemiology, and addictions/mental with extensive experience using population-level healthcare data to provide new knowledge required to develop a framework for alcohol policy change and interventions with an ultimate goal to decrease the burden of alcohol-related disease among Canadian AYAs. ",2021,2022,Queen's University,78370.37,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +C20542,202104PJT,"INTerventions, Equity, Research and Action in Cities Team (INTERACT)","Major government investments in urban design and transportation infrastructure (""built environment interventions"") are shaping Canada's cities. These investments happen outside of the health sector, yet they have an impact on both health and health equity. The INTerventions, Equity, Research, and Action in Cities Team (INTERACT) is a pan-Canadian project assessing health and equity impacts of built environment interventions. In 2017, we launched a population health intervention research program with stakeholders and community groups in Victoria, Vancouver, Saskatoon, and Montreal. Since then, we have recruited over 2200 participants to our cohorts, and done qualitative interviews with over 100 residents living near the interventions. The main goal of INTERACT is to evaluate the impact of built environment interventions on health and health equity. Building on our past work INTERACT will add to the research of healthy cities, with more attention to design, implementation, and equity. We have three objectives: 1) we will describe how health and equity are considered in the design of built environment interventions; 2) Examine the patterns of where built environment interventions are made and for who, over time; and 3) Evaluate impacts of built environment interventions on health outcomes and health equity. We study four built environment interventions, identified with city partners. In Victoria, the All Ages and Abilities Cycling Network; in Vancouver, the City Greenways Plan; in Saskatoon, the Bus Rapid Transit (BRT); and in Montreal, ecological transition and resilience policies like greening, place-making, traffic-calming, and transportation interventions. Our proposal is especially relevant in light of the challenges brought on by COVID-19, providing evidence on longer term changes physical activity, well-being, and social connectedness impacts, before and following the pandemic. ",2021,2026,Memorial University of Newfoundland,725220,Human Populations | Environment,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C20544,202111FBD,"Longitudinal Cohort Analysis of Antibody Responses Neutralization Efficiency and Long-Term Immunity in natural SARS-CoV-2 infection, Vaccination and its robustness against emerging Variants of Concern.","The pandemic of SARS-CoV-2 and it's associated disease (COVID-19) has resulted in millions of deaths and deep socioeconomical impact globally. While countries such as Canada are trying to reach a level of vaccine acquired herd immunity many questions remains on SARS-CoV-2 immunity. To answer those questions, 1,000 individuals from the Ottawa/Gatineau region have been recruited and enrolled in a longitudinal cohort study called Stop the Spread Ottawa https://omc.ohri.ca/SSO/ (SSO) for an initial period of 10 months. During this period, saliva samples have been collected to access the presence of the virus as well as monthly blood draw to test the presence of antibodies using our established high-throughput robotic testing lab. A second phase of SSO will continue to track a subset (n=300) for an additional 34 months making SSO one of the largest and longest study of SARS-CoV-2 immunity in Canada. The samples collected within this study are of extreme value due to the fact that contain baseline samples acquired before SARS-CoV-2 infection and most importantly before Vaccination. These rare samples therefore holds precious research opportunities. Some of the question we aim to answer are the following : How long does immunity last after natural infection and vaccination? Are some groups of participants mount less robust immune responses following vaccination which can lead to breakthrough infection? How does natural infection and vaccination protects against emerging variants (VOC)? Is a vaccine strategy more robust and long lasting than others? Furthermore, using this cohort, post-infection sequelae (I.e. long COVID-19, post-COVID syndrome) and the impact of auto-antibodies will be investigated. Critical information about antibody-mediated immunity will be shared with the scientific community and local/regional/national health authorities which will guide public health measures, vaccination strategy (need for booster) and VOC impact in Canada. ",2021,2024,University of Ottawa,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C20545,202104PUU,"REAC! Responsiveness of the care of newcomers to the COVID-19 pandemic in Montreal, Sherbrooke and Toronto: a mixed participatory research","Google translate:Migrant populations are among the groups most likely to have poor health. In Canada, the institutional management of the health and social services needs of these populations is supplemented by the action of community organizations. In Quebec and Ontario, they intervene in several sectors: psychosocial support, housing, food security, and job search. COVID-19 has disrupted the way these organizations operate, forcing them to adopt new ways of serving their beneficiaries in order to comply with the measures in place. This research is taking place in Montreal, Sherbrooke and Toronto, in the first two migrant-receiving provinces in Canada - and which are the most affected by COVID-19. Our study includes community stakeholders as well as policy makers and managers of health and social services networks (RSSS) in the research process. It concerns the actions implemented by them in the context of the pandemic. Three objectives are targeted: 1) to shed light on the innovations that emerge from the adaptation of the services of community organizations and the RSSS, 2) to study the needs of the beneficiaries, 3) to support the integration of promising innovations promoting intersectoral collaboration ( community-RSSS). To reach them, we will conduct interviews with officials and stakeholders, and surveys and focus groups with beneficiaries. The involvement of different partners, including the beneficiaries themselves, gives this research a significant social impact. Lessons learned from promising innovations are indeed likely to improve care beyond the context of the pandemic: decision-makers would benefit from relying more on this experience to provide appropriate, well-funded and culturally sensitive care.]",2021,2023,Université de Montréal,292300,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C20546,202107UIP,Open Sky School: Effectiveness of an intervention program involving nature to mitigate the impacts of school disruptions related to Covid-19 on the mental health and healthy lifestyles of children from disadvantaged backgrounds.,,2021,2022,CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital,118150.82,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20547,202104PJT,Examining the Impacts of the COVID-19 Pandemic Response on Health and Functioning of Canadian Children and Youth,,2021,2025,McMaster University,2453661.79,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20548,202112GSM,Caregiver burden and early readmission after ED discharge: an interrupted time series,"One-third of all patients consulting emergency departments (ED) are seniors and an additional one-third of seniors admitted to the ED report care coordination problems, chief among them are gaps in hospital discharge planning and long waiting lists to receive home care services. It remains unclear whether (1) burden of care among caregivers of elderly patients can account for varying levels of success in reducing ED visits, readmission rates, and length of stay in the hospital among this elderly population, and (2) how the COVID-19 pandemic may have moderated the relation.With a sample of approximately 4000 patients from the LEARNING WISDOM context-adapted CISSS-CA ACE (Centre intégré de santé et de services sociaux de Chaudière-Appalaches Acute Care for Elders) program we will explore whether burden of care reported by caregivers can predict admission to and early revisits to the ED among elderly patients with many different health backgrounds and complaints.We will leverage Learning Wisdoms interrupted time series to assess the CISSS-CA-ACE intervention's effects on early revisits to the ED as moderated by caregiver burden. As the CISSS-CA-ACE program was likely significantly disrupted by the COVID-19 pandemic, we also intend to conduct an additional interrupted time series over each wave of the COVID-19 pandemic.We suspect that higher indices of burden of care in the later waves of the pandemic translate to especially large rates of early readmission among elderly patients. The results from this inquiry may contribute to our understanding of individual differences in strain and burden among older adults and their caregivers are related to real-world health outcomes. ",2021,2022,Université Laval,13825,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20549,202112GSM,"Longitudinal associations between stress, anxiety and depression experienced by pregnant people during the pandemic and the development of their babies: The role of the marital relationship and social support","Google translate: Numerous studies show that a high level of stress as well as symptoms of depression and/or anxiety in pregnant people are linked to emotional, behavioral and cognitive difficulties in the child. Research shows that the COVID-19 pandemic has exacerbated rates of depression and anxiety among pregnant people. In addition, greater perceived support from the partner may contribute to improved postpartum well-being for both mother and child. A better understanding of the longitudinal links between psychosocial distress in pregnant people and the development of their babies in a pandemic context as well as the moderating role of the marital relationship and social support will serve to identify prevention targets to mitigate the negative effects of pregnancy. pandemic. Few studies have examined the well-being of pregnant people throughout pregnancy and after childbirth and some factors that may influence their well-being. Thus, the present study aims to better understand the longitudinal links between stress, depression and anxiety experienced by pregnant people in a pandemic context and the temperament and behavior of their baby. The moderating role of the marital relationship and the social support of the partner will also be examined. More than 800 people who were pregnant or less than 3 months postnatal were recruited to take part in this 2-year study. They completed online questionnaires at each trimester and at 3, 12, 18 and 24 months postnatal. These results will make it possible to identify courses of action with this clientele in a situation of vulnerability and will promote the optimal development of the child.]",2021,2022,Université du Québec à Montréal,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20551,202109EG5,Monitoring Immune Responses to COVID-19 Vaccine in People Living with HIV-1,,2021,2022,Université Laval,395000,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C20552,202104PRR,Aging and exercise: impact on the pathophysiology of ventilation-induced lung injury,"Relevance: Our research focuses on a disease called Acute Respiratory Distress Syndrome (ARDS) in which the lung has difficulty getting oxygen into the blood, and that can be caused by lung infections, such as COVID-19. Approximately 30-40% of people with ARDS will die of the disease. Importantly, one of the key treatments for ARDS is mechanical ventilation, which is a treatment to help people breathe by pushing air into the lungs. However, mechanical ventilation can also cause even more injury to the lungs. Problem to be addressed: To study ARDS and the damage caused by mechanical ventilation, we and many other laboratories use animals. Although great progress has been made, a problem with previous studies has been the standard practice of using young male animals for the experiments, even though in humans the disease occurs in both males and females and mostly within the older population. To overcome this limitation, we will investigate mechanical ventilation in older animals of both sexes that better reflect the human population. Experimental plan: For our studies, we will use aged male and female mice to study the development of lung injury. For example, we will utilize 22 month old mice, which is comparable to a 65 year old human, and study how the lungs of these animals respond to damage by mechanical ventilation. We will also examine the effects of exercise (running on a treadmill), since studies have demonstrated that regular exercise can protect against respiratory disease. Further, we will investigate various cellular pathways and molecules in the lung that are known to be important in ARDS. Impact: The novelty of our study is that we take a ""real life"" approach to scientific laboratory studies. With a better understanding of actual population-based issues that impact the development and/or the severity of ARDS, we will be better equipped to develop strategies to improve outcomes associated with this disease. ",2021,2022,London Health Sciences Centre Res. Inc. (Ont.),79000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2021 +C20553,202104PJT,"Can ""Awake Extracorporeal Life Support"" Prevent Ventilator-Induced Diaphragm Atrophy and Injury in Patients with Acute on Chronic Respiratory Failure?","The diaphragm is the main breathing muscle. Patients with diaphragm weakness experience serious difficulties with breathing and exercise. A strong diaphragm makes patients more resilient to acute respiratory problems and maintaining diaphragm strength in respiratory failure patients is vitally important to help patients recover from lung failure due to pneumonia, Covid-19, and other lung diseases. Being on a ventilator for lung failure can cause diaphragm weakness; this might be prevented by a different form of artificial lung support that avoids the need for the breathing machine. In patients who require artificial lung support before transplantation, we will study diaphragm tissue obtained during the transplant surgery to determine whether the use of artificial lung support can avoid the loss of diaphragm muscle bulk and reduce the amount of diaphragm muscle injury that occurs with the artificial breathing machine. Answers to these questions will lead to new methods for treating patients with lung failure focused on improving and maintaining diaphragm muscle bulk and strength. These methods will enable us to improve recovery and quality of life for patients with acute and chronic lung diseases. ",2021,2024,University Health Network,241740,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C20554,202104PJT,Ontario's Opioid Drug Observatory: Generating evidence on the evolving opioid crisis to inform and evaluate drug policy and clinical practice in Ontario,"The harms related to opioid use continue to climb across Canada, and the arrival of the COVID-19 pandemic has further worsened this crisis, with many communities reporting record numbers of harms. As the factors influencing opioid-related harm have shifted in the past decade, so has the clinical response, with the arrival of newer treatment options and harm reduction services. As Canada grapples with challenges to providing accessible services in the midst of this overdose-COVID-19 syndemic, more research is urgently needed to monitor and evaluate the evolving overdose crisis. In 2017, the Ontario Opioid Drug Observatory (OODO) was funded to inform and evaluate opioid policy across Ontario. As this crisis has worsened, the need for timely, high quality evidence to inform policy has increased. Through linkage of a broad repository of health care data, our proposed work will describe provincial patterns of opioid use, harms, and access to treatment and harm reduction services; assess the effectiveness and accessibility of treatment and harm reduction services; and identify modifiable factors that can influence patterns of healthcare use and patient outcomes among people experiencing serious opioid-related harms. The proposed research questions have been guided by a diverse group of patients, researchers, clinicians, harm reduction workers, and policy-makers who comprise the OODO Steering Committee. This committee will continue to oversee this work to ensure broad relevance, uptake and dissemination. As Canadian policymakers are faced with the challenge of rapidly adapting to a changing overdose crisis that is being worsened by the COVID-19 pandemic, our work will provide a comprehensive understanding of the crisis in Ontario. Our team of experts will optimize the use of high-quality datasets to inform and evaluate national and provincial prescribing policies and clinical decision-making with the potential for enormous public health impact over the coming years. ",2021,2025,Unity Health Toronto,791700.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20555,202111FBD,Broad spectrum antivirals against RNA viruses with high epidemic potential,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease of 2019 (COVID-19), revealed the debilitating potential of RNA viruses in the absence of effective medical countermeasures. Neither vaccines nor antiviral drugs were available when the World Health Organization (WHO) declared the pandemic. While the rapid development of COVID-19 vaccines is currently viewed as a ""game changer"", the toll of the disease has been enormous with > 3.8M deaths worldwide and >25,000 in Canada. To be prepared for future outbreaks or another pandemic, we need effective tools for immediate use that help to bridge the time required for the development of vaccines. These tools are potent antiviral drugs. In the case of HIV, antiviral drugs have saved millions of lives even in the absence of vaccines. Here I propose to lay the foundation for the development of broad-spectrum antivirals that can serve as the first line of defense in outbreak situations with RNA viruses. My previous publications defined the mechanism of action (MOA) for two different antivirals, remdesivir (RDV) and molnupiravir (MLP), against the RNA-dependant RNA polymerase (RdRp) of SARS-CoV-2. The RdRp is the engine that drives viral propagation, and a logical antiviral target. RDV is currently the only approved antiviral for COVID-19 treatment, while MLP is in phase 3 clinical trials. RDV and MLP are broad-spectrum antivirals inhibiting multiple RNA viruses, however the MOA remains unknown. Our lab has worked diligently to express and characterize an expansive platform of RdRp enzymes from RNA viruses the WHO has classified as priority pathogens. This project will elucidate a unified MOA for RDV and MLP across multiple viral RdRps, ultimately assisting in the development of next generation antivirals. My strong history of work with the SARS-CoV-2 RdRp has positioned me to lead this project. ",2021,2024,University of Alberta,82950,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +C20556,202111WI2,Effets d'une intervention musicale personnalisée sur les répercussions de la COVID-19 en santé mentale des personnes âgées,,2021,2023,Université de Montréal,244098.15,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20557,202111FBD,"A systemic approach to understanding cancer caregiving in Canada during COVID-19: An integrative, multi-method qualitative study",,2021,2024,York University,82950,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20558,202112GSM,Identification of the Immunological Mechanisms that Regulate SARS-CoV-2 Vaccine Durability,,2021,2022,Dalhousie University,13825,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +C20559,202112GSM,Using cell-free DNA as a Biomarker for Pulmonary Vascular Disease in Patients with Long COVID,,2021,2022,University of Calgary,13825,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2021 +C20560,202106FSS,Living systematic review on thoracic imaging for diagnosis of coronavirus disease 2019 ( COVID-19),,2021,2021,University of Ottawa,4740,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C20561,202112GSM,"Investigation of the long-term clinical disease, pathogenesis, and immune responses following SARS-CoV-2 infection in Syrian hamsters and humans.",,2021,2022,University of Saskatchewan,13825,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2021 +C20562,202104PJX,Coronavirus Crisis Competence Among Sexual and Gender Minorities,,2021,2022,CIUSSS de l'Est-de-l'lle-de-Montréal-Santé Mentale,79000,Unspecified,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,,,2021 +C20563,202104PJT,Immunovirological determinants of breakthrough COVID-19 disease in vaccinated or previously infected individuals,,2021,2026,Centre hospitalier de l'Université de Montréal (CHUM),755437.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20564,202112GSM,Investigating whether stress related to the COVID-19 pandemic negatively impacted parent-child attachment in infants,,2021,2022,Ryerson University,13825,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20565,202110QA3,Telemedicine in the care of people living with dementia and their caregivers in the rural and urban community of Canada during and beyond the COVID-19 pandemic,,2021,2022,McGill University,0,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Rural Population/Setting | Urban Population/Setting,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20566,202112GSM,Errant epitopes from arginine methylated SARS-CoV-2 proteins predisposing to autoimmune diseases,,2021,2022,McGill University,13825,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20567,202104PJT,"REVIVe: Frailty, Rehabilitation, and Hospitalization Outcomes in Adult and Pediatric Survivors of COVID-19",,2021,2024,McMaster University,583196.96,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +C20568,202104PUU,"Pregnant during the COVID-19 pandemic: A prospective, multi-method study examining the impact of chronic prenatal stress on child outcomes.",,2021,2025,Mount Saint Vincent University,430550,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20569,202112GSM,Adaptation of a Self-Compassion Intervention for Treating Psychological Symptoms of Long COVID,,2021,2022,University of Alberta,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20570,202112GSM,Incidence de la pandémie de la COVID-19 sur les processus d’inhibition cognitive chez une population atteinte de la maladie d’Alzheimer,,2021,2022,Université de Montréal,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20571,202112GSM,Investigating the immunosuppressive effects of Severe Acute Respiratory Syndrome Coronavirus 2 Non-Structural Protein 2 on type I interferon expression via interaction with the 4E-Homologous Protein/Grb10-interacting GYF protein 2 complex,,2021,2022,McGill University,13825,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20572,202109PJT,"Creating an Evidence-Informed, Accessible, Clinically Useful and Personalized Virtual Mental Health Support Framework for School-Age Children on the Autism Spectrum: Building from Pandemic e-Support Experiences",,2021,2025,Centre for Addiction and Mental Health (Toronto),519741,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20573,202112GSM,Investigating the Impact of Social Isolation Stress on Hippocampal Neural Activity,,2021,2022,University of Alberta,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20574,202111FBD,Detection and differentiation of SARS-CoV-2 variants of concern using isothermal amplification and CRISPR effectors,,2021,2024,Université Laval,82950,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C20575,202102VS1,COVID-19 Variant Supplement - Supporting mental health and preventing moral injury among long term care+ workers: A mixed methods tool kit development and implementation study,,2021,2022,University of Calgary,39500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +C20576,202109PJT,Evaluating the ongoing impact of COVID-19 on youth substance use and mental health trajectories over time: renewal of the COMPASS prospective cohort.,,2021,2026,University of Waterloo,2018529,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Drug users,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20577,202104PJT,Advancing methods and analyses to support evidence-informed decision-making on the coordinated use of travel-related measures during public health emergencies of international concern: Lessons from the COVID-19 pandemic,,2021,2024,Simon Fraser University,510674.96,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2021 +C20579,202109PJT,Targeting SARS-CoV-2 Main protease and variants for effective antiviral development,,2021,2026,University of Alberta,679893.75,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +C20580,202109PJT,COVID-19 Vaccine-Induced Inflammatory Heart Disease Prevalence Registry and Cohort Study (COVID-VIHPR),,2021,2025,Ottawa Heart Institute Research Corporation (Ontario),640611,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Epidemiological studies | Vaccines research, development and implementation",Disease surveillance & mapping | Adverse events associated with immunization,2021 +C20581,202112GSM,"Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons with Post-COVID-19 Condition",,2021,2022,University of Toronto,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation",Post acute and long term health consequences | Prophylactic use of treatments,2021 +C20582,202112GSM,Impacts of athletic identity on sports participation and sport drop out in secondary-school athletes: return-to-play following COVID-19,,2021,2022,University of Victoria,13825,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C20583,202112GSM,Understanding the burden of SARS-CoV-2 infection among South Asians in Ontario,,2021,2022,McMaster University,13825,Human Populations,Asian,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease surveillance & mapping,2021 +C20584,202112GSM,"Role of the signalling lymphocytic activation molecule (SLAM)â€""associated protein (SAP) in the host response and intra-host evolution of SARS-CoV-2",,2021,2022,McGill University,13825,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20585,202112WGC,NeuroCovid: European Solution for the Global Problem of dementia and Neurodegeneration following COVID-19 (EU-Connect),,2021,2022,University of Toronto,0,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Post acute and long term health consequences,2021 +C20586,202110MFE,Leveraging Longitudinal Data to Understand Youth Mental Health Care Utilization during the COVID-19 Pandemic,,2021,2022,University of Calgary,43450,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +C20587,202112GSM,Examining the role of microglia in long-term neuropathology following acute SARS-CoV-2 infection using neural organoids,,2021,2022,University of Toronto,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",,2021 +C20588,202112GSM,"Investigating the role of microglia in COVID-19 associated neuroinflammation, using human brain organoids.",,2021,2022,University of Toronto,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",,2021 +C20589,202112FO1,The Mental Wellness of Citizens of the Métis Nation: Before and during COVID-19,,2021,2022,Direct Payment,197500,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20590,202112WGC,Strategizing Transdisciplinary Research Priorities around the impact of COVID-19 control measures on people with dementia and informal carers living at home: A European and Global South perspective,,2021,2021,University Health Network,26255.65,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +C20591,202109IHT,Canadian children and youth’s movement and play during the pandemic,,2021,2022,Dalhousie University,553,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C20592,202112GSM,How does the SARS-CoV-2 antibody response shape patient outcomes? A longitudinal study to evaluate the SARS-CoV-2 antibody response and associations with physiological response and clinical outcomes,,2021,2022,University of Toronto,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +C20593,202111FBD,SARS-CoV-2 infection disassembles processing bodies to manipulate antiviral responses,,2021,2024,University of Calgary,82950,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +C20594,202109AI1,Behavioral and Health Effects of Alcohol Policy Changes During COVID-19 in Canada,,2021,2022,Memorial University of Newfoundland,79000,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20595,202104PJT,Estimating the value and long-term impact of implementing Risk Mitigation Guidance to reduce the harms of substance use disorders during the COVID-19 pandemic: A simulation modeling analysis,,2021,2024,Simon Fraser University,731263.5,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20596,202112GSM,Canadian Survey of Pediatric Eating Disorder Programs: Understanding how COVID-19 Accelerated Virtual Care Implementation,,2021,2022,Université de Montréal,13825,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20597,202111FBD,Improving the Clinical Efficacy and Safety Profile of Repurposed COVID-19 Drugs,,2021,2024,University of Toronto,82950,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +C20598,202112GSM,Development of a Small Molecule Screen for Coronavirus (CoV-2) Frameshifting Modulators Using Yeast,,2021,2022,University of British Columbia,13825,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C20599,202109ER5,Noochokooyishi Anavaan (The Ways Forward): An equity-focused approach on the impact of the COVID-19 pandemic and perspectives on future pandemic responses among Métis in Alberta,,2021,2022,University of Alberta,192760,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2021 +C20600,202112GSM,Development of an in vitro pseudo-neutralization assay to assess the efficacy of anti-SARS-CoV-2 antibodies,,2021,2022,Université de Montréal,13825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Immunity | Disease pathogenesis | Supportive care, processes of care and management",2021 +C20601,202109EG9,Modulation des réponses immunitaires à la vaccination contre la COVID-19 par une intervention sur le microbiote intestinal : un essai randomisé contrôlé.,,2021,2022,Université de Sherbrooke,789849.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase),2021 +C20602,202104GA4,Évaluation de l'efficacité des probiotiques sur les affections post-COVID-19.,,2021,2022,Université de Sherbrooke,787845.67,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +C20603,202112GSM,"Impacts of the COVID-19 pandemic on sexual and reproductive health services and well-being amongst urban Indigenous women â€"" Implications for Indigenous well-being and reproductive justice",,2021,2022,Simon Fraser University,13825,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Indigenous People | Women | Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20604,202112GSM,Intimate Partner Violence Among the LGBTQ+ and General Population During COVID-19,,2021,2022,University of Toronto,13825,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20605,202107UIP,"Comprendre et atténuer les répercussions de la pandémie de COVID-19 sur les jeunes, les familles et les milieux scolaires en région éloignée",,2021,2022,Université du Québec à Chicoutimi,64202.51,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Rural Population/Setting,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",,2021 +C20606,202112GSM,Comparative Transcriptional Profiling of Both Immortalized Human Lung Cells and Patient-Derived Lung Organoids Infected with Circulating SARS-CoV-2 Variants of Concern (VOCs),,2021,2022,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2021 +C20607,202107UIP,Le conflit travail-famille comme déterminant social genré de la santé mentale des parents et des enfants suivant la pandémie COVID-19,,2021,2022,McGill University,117514.08,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Rural Population/Setting,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",,2021 +C20608,202111FBD,Can Graded Exercise Reduce Symptoms of Chronic Pain and Long COVID as well as Promote Long-Term Recovery?,,2021,2024,University of Regina,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C20609,202102HF1,AI-driven solutions to mitigate the social and psychological impact of COVID-19,,2021,2023,"Ontario Agency for Health Protection and Promotion (Toronto, Ontario)",85715,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20610,202104PJT,Defining the role of cardiovascular co-morbidity in COVID-19 disease pathogenesis,,2021,2026,University Health Network,840046.5,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2021 +C20611,202110QA2,Access to care and the economic burden of tuberculosis in Ontario during the COVID-19 pandemic: illuminating inequities to support public health policy,,2021,2022,University Health Network,78951.81,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Policy research and interventions | Indirect health impacts",2021 +C20612,202112GSM,Antibiotic Prescribing in Patients with COVID-19: A Rapid Review with Meta-Analysis and Meta-Regression,,2021,2022,University of Ottawa,13825,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +C20613,202109IHT,What to expect when visiting the ED during the COVID19 Pandemic,,2021,2022,University of Alberta,553,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20616,202112GSM,Development of a serological microfluidic assay for the rapid detection of interferons in COVID-19 patients,,2021,2022,McGill University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20618,202112GSM,Phosphorylation of the SARS-CoV-2 nucleocapsid (N) protein as a regulation mechanism for N-mediated processing body disassembly,,2021,2022,University of Calgary,13825,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +C20619,202109PJT,To enhance prenatal education program interrupted by COVID-19 in remote and rural First Nations communities by expanding remote education through two-eyed seeing framework to improve maternal child health,,2021,2026,University of Manitoba,912568.5,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Indigenous People | Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +C20620,202111FBD,Assessing contractile dysfunction due to SARS-CoV-2 infection in a heart-on-a-chip platform,,2021,2024,University of Toronto,82950,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2021 +C20621,202110QA4,The Effects of the COVID-19 Pandemic on Physician Delivery of Virtual and In-person Mental Health Care Services across Reformed Primary Care Payment Models in Ontario,,2021,2022,Centre for Addiction and Mental Health (Toronto),79000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians | Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20622,202112GSM,"Harnessing pre-existing immunity to enhance the immunogenicity of an adjuvant-free, immuno-targeting subunit vaccine against SARS-CoV-2",,2021,2022,University of Toronto,13825,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2021 +C20623,202112GSM,Investigating Anti-Coronavirus Antibodies to SARS-CoV-2 Infections in Prenatal Women,,2021,2022,University of British Columbia,13825,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +C20624,202104PJT,Addressing household food insecurity in Canada: learning from the COVID-19 pandemic,,2021,2023,University of Toronto,389805.75,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +C20625,202110MFE,Stress Resilience during the COVID-19 Pandemic - Understanding the Role of the Prenatal and Early Life Gut Microbiome on Neurodevelopmental and Mental Health Outcomes.,,2021,2024,University of Calgary,106650,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20626,202112WGC,Dementia and COVID-19: Experiences in Care (DECOVEXP),,2021,2022,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20627,202112GSM,How the COVID-19 pandemic has influenced women's employment and their health: An inquiry into their lived experiences,,2021,2022,University of Ontario Institute of Technology,13825,Human Populations,Unspecified,Unspecified,Unspecified,Women | Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts | Indirect health impacts,2021 +C20628,202104PUU,Functional analyses of pathogenicity determinants of emerging SARS-Coronavirus-2 variants,,2021,2022,University of Saskatchewan,79000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +C20629,202112GSM,Substance Use Disorder and COVID-19 Related Health Outcomes,,2021,2022,McGill University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2021 +C20630,202104PJT,Co-Creating a Rehabilitation Strategy to Support the Psychosocial Recovery of Individuals with Long COVID,,2021,2023,"Sunnybrook Research Institute (Toronto, Ontario)",175261.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +C20631,202111FBD,"The association between COVID-19 severity, human leukocyte antigen alleles and genomic copy number variants.",,2021,2024,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2021 +C20632,202112GSM,Substance Misuse and the Pandemic: A Qualitative Study of BC Paramedics' Attitudes and Interactions with Overdose Patients During COVID-19,,2021,2022,Simon Fraser University,13825,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +C20633,202111FBD,"Real-time epidemiological intelligence to inform control of SARS-CoV-2: improving the precision, validity, and granularity of estimates of the effective reproduction number in Canada",,2021,2024,McGill University,82950,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics,2021 +C20634,202112GSM,Impact of COVID-19 on Quality of Life of Seniors with Eye Disease and Implementations to Improve Wellness,,2021,2022,Western University,13825,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Indirect health impacts,2021 +C20635,202111FBD,"Artificial intelligence-based analysis of cough for tuberculosis and COVID-19 screening in Lima, Peru",,2021,2024,McGill University,82950,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +C20636,202104GA3,Addressing socioeconomic and racial/ethnic inequities in COVID-19 vaccine hesitancy among parents and adolescents,,2021,2022,Université de Montréal,378161.15,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Health Systems Research","Vaccine/Therapeutic/ treatment hesitancy | Medicines, vaccines & other technologies",2021 +C20637,202203PJT,Preparing for the Recovery from the Effects of the PAndemic on cancer control using Real-world Evidence in Canada (PREPARE-Canada),,2022,2027,"Ontario Institute for Cancer Research (Toronto, Ontario)",883575,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20638,202203PEE,Molecular determinants of differential accessory protein-mediated pathogenesis during SARS-CoV-2 and MERS-CoV infections,,2022,2024,University of Saskatchewan,308000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2022 +C20639,202203PEE,Evaluating the impact of COVID-19 vaccine policies on vaccine equity: A multi-province comparative study,,2022,2024,University of Calgary,308000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +C20641,202203ECP,Prize 202203PJT - An intersectional investigation of women's experiences of overlapping overdose and COVID-19 public health crises,,2022,2023,University of British Columbia,77000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20644,202203PEE,Synthesizing evidence to inform decision-making in the context of a pandemic: balancing efficiency with methodological rigour,,2022,2024,McMaster University,264943.14,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +C20645,202202PCS,Building Social Media Communications Capacity for Public Health Emergency Response and Preparedness in British Columbia,,2022,2023,Simon Fraser University,18989.74,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Research on Capacity Strengthening,Institutional level capacity strengthening,2022 +C20648,202203PJT,"Developing Social Connection Guidelines to Help Canadians Build Happier, Healthier, and More Inclusive Communities in the Late Pandemic Period",,2022,2027,Simon Fraser University,586105.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2022 +C20649,202203PTT,Characterization of the antiviral mechanisms of cyclophilin inhibitors against coronavirus infection,,2022,2025,Queen's University,231000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +C20654,202203PEE,Addressing the COVID-19/malaria interface at health centres in the Democratic Republic of Congo,,2022,2024,McMaster University,200200,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2022 +C20661,202204CN3,Canadian Critical Care Trials Group COVID-19 Response: defining critical care capacity in Canada; testing treatments through large-scale adaptive clinical trials; & establishing the evidence base to inform clinical and health system management decisions,,2022,2023,"Sunnybrook Research Institute (Toronto, Ontario)",770000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Health Systems Research | Therapeutics research, development and implementation",Health leadership and governance | Clinical trial (unspecified trial phase),2022 +C20663,202203PJT,Prenatal exposure to maternal SARS-CoV-2 infection and early childhood development,,2022,2027,University of Calgary,689188.5,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Post acute and long term health consequences,2022 +C20665,202207TAA,COVID-19 effects of HIV-affected youth in South Africa through participatory visual methodologiesmethodolgies,,2022,2023,University of Toronto,1925,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20669,202207TAA,Access to HIV and sexual healthcare during COVID-19: gay and bisexual men’s experience,,2022,2023,Western University,2079,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20674,202203PJT,Pre-clinical development of broad-spectrum antiviral strategies against human respiratory viruses of pandemic concern,,2022,2026,University of British Columbia,728066.57,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +C20677,202203PEE,STARS: Surveillance and Testing for Antiviral Resistance in SARS-CoV-2,,2022,2024,"Sunnybrook Research Institute (Toronto, Ontario)",308000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Phase 4 clinical trial,2022 +C20679,202203PJT,"Optimizing pandemic preparedness through ongoing assessment of public attitudes, intentions and behaviours in relation to COVID-19 prevention measures and their impacts: Extending the iCARE Study",,2022,2025,Université du Québec à Montréal,733368.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +C20682,202207TAA,Delivering COVID-19 vaccine to people living with HIV through an AIDS service organization partnership,,2022,2023,Direct Payment,1925,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,"Medicines, vaccines & other technologies",2022 +C20687,202202PCS,Advancing pandemic capacity in pediatric care,,2022,2023,University of Calgary,19250,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +C20690,202205OTT,Canadian ADAptive Platform Trial of COVID-19 Therapeutics in Community Settings (Can-ADAPT COVID),"While public health measures and vaccines have reduced the spread of SARS-CoV-2, most scientists predict this virus will be endemic and new variants will emerge. Effective and affordable medications in community settings are needed. Adaptive platform trials are designed to compare multiple therapies and allow us to respond to the dynamic nature of the COVID-19 pandemic. Building on our team's experience leading other adaptive platform trials, Can-ADAPT COVID will evaluate the clinical and cost-effectiveness of oral medications for SARS-CoV-2 in non-hospitalized patients. In collaboration with patient and community partners we will engage diverse populations. We anticipate beginning by evaluating nirmatrelvir/ritonavir (Paxlovid™), provided by the Public Health Agency of Canada, but additional therapeutics will be added through a transparent Canadian COVID-19 Therapeutics Advisory Panel (modelled after the UK). Can-ADAPT COVID will closely work with adaptive platform trials in the UK and European Union to enable the federation of our trial data to support faster and more powerful statistical analyses. Our primary outcome will be hospitalization (+death) at 28 days, and key secondary outcomes will include time to recovery and impact on ""long COVID"". We will also assess changes in quality of life and health resource utilization, to evaluate the cost-effectiveness of each therapeutic. We will use numerous approaches to recruit, including a multi-faceted public communication strategy and outreach through primary care, out-patient clinics and emergency departments. A unique strength is additional prospective recruitment using EMR data from primary care research networks in Ontario, Quebec, Alberta, BC, Manitoba, Nova Scotia and Newfoundland. Can-ADAPT COVID will result in national adaptive platform trial infrastructure beyond the COVID-19 pandemic, for influenza and other upper respiratory pathogens, and build capacity to efficiently study therapeutics for other diseases.",2022,2023,Unity Health Toronto,3850000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +C20691,202203PJT,Adapting genetic clustering techniques to SARS-CoV-2,"One of the positive outcomes of the ongoing SARS-CoV-2 pandemic has been the rapid collection and sharing of virus genomc data. Today, there are over 9 million SARS-CoV-2 genomes from around the world in public databases. This abundance of data has also created tremendous new challenges for genomic epidemiology - the use of genetic sequences to reconstruct the spread and adaptation of an infectious disease. The purpose of this project is to contribute to the global effort to update the computational toolkit for genomic epidemiology for the SARS-CoV-2 pandemic by focusing on clustering methods. Genetic clustering is a fundamental category of methods for analyzing sequences where we collect similar observations into groups. Clusters are intuitive and have a broad range of applications. For the study and management of infectious diseases, for example, we use clusters to detect outbreaks, to find associations between risk factors and the spread of disease, and to reconstruct how different infections are related back in time. Clusters are also a useful device for reducing large data sets while preserving the essential information. Many of the standard clustering methods used for infectious disease were developed and honed on HIV-1 sequences, not only because of the enormous global health burden of this disease, but also because these data are abundant around the world. Our specific objectives are to: (1) adapt methods from network science to partition large databases of SARS-CoV-2 genomes into clusters that are calibrated to measure the impact of age, location and other risk factors on transmission rates; (2) develop fast, approximate methods to extract epidemiological information, such as the number of unsampled infections, from cluster-based trees updated in real time; and (3) to adapt a method from dynamic social network analysis to reconstruct the role of recombination (the exchange of fragments between genomes) in the evolutionary history of coronaviruses. ",2022,2027,Western University,459459,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2022 +C20692,202202PCS,Health Equity Methods and Measures Considerations for Guidelines in an Age of Digital Transformation,"Artificial intelligence and digital transformation are reshaping the next generation of healthcare. Technology presents both opportunities and threats to the health of groups of people who may suffer avoidable, unfair, or remedial health differences or inequities. The COVID-19 pandemic has shone a bright light on the importance of health literacy, knowledge transfer, and health equity considerations for interventions and policies. Trustworthy health information and co-designed guidelines can help build health literacy in communities, and along with access to smart phones and the internet, could help reduce the digital divide. Guidelines for the public and community practitioners need to be part of a broader strategy for social impact, not just for health services. We believe this timely extension of our GRADE health equity methods for guidelines could play a role in improving digital uptake of community recommendations. As new community care interventions are developed and evaluated, we must be ready with equity methods and measures relevant for the digital age. This meeting grant will bring together international methods experts and organization leaders to help identify health equity methods, measures and considerations for digital community interventions including patient access, transitions, care coordination, self-management, and patient experience. Using a survey, consensus method and workshop, we will identify areas related to community interventions and guidelines that would benefit from explicit health equity considerations to improve health and mitigate negative digital divide impacts on health for communities. ",2022,2023,Western University,7623,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Health Systems Research",Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in Governance | Approaches to public health interventions | Health service delivery,2022 +C20693,202205ORN,COVID-19 seroepidemiology in children Using Retrieved POPCORN site Leftover Samples (CURNLS),,2022,2023,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",0,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease surveillance & mapping,2022 +C20694,202202PCS,Establishing stakeholder priorities for evidence-informed strategies to improve the value of healthcare systems,"The implementation of healthcare reform in Canada has been notoriously challenging. Reforms are more likely to succeed because of timing or context changes, such as crises or actions taken by new governments as well as engaging patients and providers in the policy process. The COVID-19 pandemic is an unprecedented crisis. It has exposed and deepened health, race, and gender inequities, and crystalized new challenges like virtual health, mental health, and long term care that require immediate action and open the window for successful healthcare reform. We propose holding a priority setting workshop with a representative partner panel to identify ten reforms that address current needs and are informed by evidence of effectiveness and feasibility. Public, researcher, provider, and policy maker partners will be assembled for a one-day workshop. We will engage 30 partners with a range of knowledge from different geographic locations and health care settings across Canada. Prior to the workshop we will identify a list of potential reform options based on evidence of need, effectiveness, and feasibility. Ten of these potential strategies will be identified as priorities at the workshop, resulting in a list of evidence-informed strategies for healthcare reform in Canada that are acceptable and important to all stakeholders. The ten strategies identified at the workshop will be evaluated to estimate their impact on costs, quality, health outcomes, and equity and to determine any adaptations needed for implementation in provinces and territories. The 2-6 most promising strategies will be presented to policy makers at a National Health Policy Forum in January 2023. By taking advantage of the COVID-19 crisis and bringing together the public, providers, researchers, and policy makers to identify strategies for the ""new normal"", there is potential to facilitate healthcare reforms that meet the needs of Canadians, the health care system, and decision makers.",2022,2023,University of Calgary,7700,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health leadership and governance,2022 +C20695,202203PEE,Investigating variation in the inpatient allocation of scarce COVID-19 therapeutics: Equity and Clinical Outcomes,"The COVID-19 pandemic resulted in an urgent need for effective therapeutics to treat hospitalized patients with severe infections. In less than two years, new drugs were developed and existing medications were repurposed to provide a range of effective treatment approaches. However, many of these medications were in extremely short supply as there was intense global demand and only limited production capacity. This resulted in an unprecedented situation where multiple lifesaving drugs for the same condition were in short supply. The impact of drug shortages on the equity and quality of inpatient care for COVID-19 is unknown. It is clear that marginalized populations have faced a disproportionate impact from COVID-19, and inequitable allocation of scarce COVID-19 therapies has already been established in the USA. In a Canadian context, there is a pressing need to understand how patient, hospital, and regional factors intersected with inequity in medication use. Our first aim is to investigate the equitable allocation of scarce COVID-19 therapies in 33 Ontario hospitals representing ~65% of all adult medical/intensive care beds in the province. Our second aim is to develop a novel ethical framework for when multiple medications for the same condition are in short supply. A panel of international experts and local patient partners will guide the development of this framework and will be informed by an international scoping review of drug allocation frameworks used during the COVID-19 pandemic, and a survey of clinicians who have first-hand experience with these drug shortages. Our third aim is to use advanced methods in simulation modeling to estimate how this novel drug allocation framework might affect equity of drug allocation and clinical outcomes. The overarching goal of this research is to better understand how to deliver effective and equitable hospital care in situations when key therapeutics are scarce and in high demand.",2022,2024,Unity Health Toronto,308000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management | Research to inform ethical issues | Health Systems Research,"Supportive care, processes of care and management | Research to inform ethical issues in Research | Medicines, vaccines & other technologies",2022 +C20696,202202PCS,Elevating youth voice on mental health: Mobilizing co-created knowledge translation resources for Canadian secondary schools,"Schools are consistently identified as an ideal context to equitably address youth mental health (MH). However, in our research and youth engagement work, youth have expressed several barriers to accessing support within schools. The COVID-19 pandemic has further highlighted the importance of the school context, and exacerbated pre-existing concerns, inequities in MH, and access to support. Moreover, youth have been consistently left out of conversations, despite recognition of the value of engaging youth to ensure research reflects their varied experiences and resultant resources meet the diverse needs of youth. This project aims to elevate youth voice through the development and dissemination of resources to improve how we support youth MH in secondary schools. We aim to co-develop and disseminate with youth (primary audience; engagement of two youth engagement committees) and school partners, namely teachers (secondary audience; engagement of a teacher advisory committee): 1) A social media suite of resources (posts, stories, reels) for Canadian secondary schools that includes MH statistics, our secondary qualitative findings, and information on available supports and how to access them. 2) A school MH brochure (2-3 pages) for Canadian secondary schools that shares national-, provincial-, and school- and community- specific MH resources. The brochure will be populated with existing national and provincial resources (e.g., Kids Help Phone, Youthspace.ca), with space allocated for schools to include school- and community-specific MH resources. 3) A national webinar and website to further disseminate resources. The webinar will bring together diverse stakeholders (e.g., school boards, policy makers, researchers, clinicians) to discuss Canadian youth MH with guest speakers (including youth) and introduce developed resources. A website will be co-developed with youth to host the freely available resources.",2022,2023,Brock University,7661.5,Human Populations | Other,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Social impacts | Community engagement,2022 +C20697,202203PJT,Developing collaboratively a shared decision making tool for home-based videoconferencing versus in person care in child and youth mental health,"In response to the COVID-19 pandemic, the switch from in-person to virtual care has resulted in an unprecedented mass adoption of home-based videoconferencing (HBVC), using personal devices (e.g., computers, tablets, smartphones) for Child and Youth Mental Health (CYMH) care. The pandemic experience showed that the experiences of patients and families were largely positive, and that HBVC can be combined with in-person CYMH care. Most mental health services aim at implementing a sustainable hybrid model, which will improve delivery and quality of care, costs, patient engagement, and access inequities. However, there is presently no tool to help youth, parents and mental health care providers (MHCPs) to decide whether a consultation should be done in person or through HBVCs. We will build a shared decision making tool (SDMT) supported by an educational website to support this decision, which is the cornerstone of the hybrid model. We have set up a network that comprises key CYMH university centers from 6 regions across Canada, the Ontario Centre of Excellence for Child and Youth Mental Health, family advisory councils, family and young patient organizations. The project has two phases: Exploration and Design-build. In the Exploration phase, we will use surveys and semi-structured interviews to map decision needs on health quality outcomes evaluated by parents/guardians, children/youth, MHCPs. We will further explore the decision needs in focus groups. In parallel, we will identify contents for the educational website and the different rules governing HBVC across Canada. On this basis, in the Design-build phase, a steering group made up of knowledge-users and researchers, supported by web designers, will plan a prototype SMDT and a website blueprint. We will reach consensus on key aspects of the tools by using the nominal group technique. We will test the final SDMT and supporting web site for acceptability and usability.",2022,2024,Children's Hospital of Eastern Ontario Research Institute Inc,326923.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2022 +C20698,202203PEE,Ventilation Effectiveness in Reducing Aerosol Particle Concentrations in Classrooms and Graduate Student Offices Pertaining to the COVID-19 Pandemic,"The SARS-CoV-2 virus can be spread by inhalation of infected saliva aerosol particles produced when coughing, sneezing, laughing, singing, talking, or breathing. Indoors, these fine particles will continue to spread through the air in the room and a person can be exposed by a nearby infected person speaking or coughing. In this research, our motivation is to investigate the spread of airborne saliva aerosol particles in classrooms and graduate student offices. Graduate student offices can also also be considered as a good representative of any closed office space. The testbed will be classrooms and offices at the Faculty of Science at McGill University. While the amount of endogenous saliva aerosols is small compared to the overall values of particle concentrations in the air, it is these human-produced saliva particles that are of concern for airborne transmission of COVID-19. Therefore, we propose measurements that will estimate the amount of endogenously versus exogenously generated aerosol particles in occupied classrooms and offices. The classroom measurements will consider the following six occupancy scenarios: (1) 20 males and ventilation system on; (2) 20 females and ventilation system on, (3) 10 males and 10 females and ventilation system on; and (4-6) same as (1-3) but ventilation system off. In all cases, a lecturer will be an additional person in the classroom giving a 30 min talk. The measurements will be initiated 15 min before people enter the classroom to estimate the ambient (i.e., exogenous) concentration values of aerosols. Moreover, the measurements will be performed at different heights and locations in the investigated rooms to estimate how the concentrations vary spatially. In addition, we shall measure air temperature, relative humidity, and CO2 concentrations to support the interpretation of aerosol concentration data. The office measurements will be performed with 4 graduate students in an office with and without a ventilation system. ",2022,2024,McGill University,127050,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +C20699,202202PCS,Establishment of Emerging Practices and Research Priorities for Telerehabilitation in Solid Organ Transplantation,"Solid organ transplantation (SOT) is a life saving procedure for many Canadians with end stage organ dysfunction. The main goals of SOT are to improve quality of life, physical function and daily activities, which is supported by pre- and post-transplant rehabilitation. In-person, hospital-based programs have been the standard way of delivering rehabilitation for SOT patients. However, these programs had to quickly change to a virtual delivery model (i.e. tele-rehabilitation) due to restrictions on in-person delivery from COVID-19. Telerehabilitation programs are being used across the country both clinically and in research, but with a variety of practices. Furthermore, stronger research evidence is needed to determine which approaches to telerehabilitation may be most effective in SOT. We propose to hold a 2-day virtual meeting in October 2022 for ""Establishment of Emerging Practices and Research Priorities for Telerehabilitation in SOT."" This meeting will bring together over 30 adult and pediatric researchers, clinicians and patient and family partners across SOT (heart, lung, liver and kidney) to develop a common research strategy. The objectives of the meeting are: 1) increase communication and collaboration between experts and various stakeholders across SOT programs 2) identify opportunities and available resources for virtual care to help with access to rehabilitation (i.e. rural-urban, income); 3) identify important research questions and clinical priorities in telerehabilitation. The anticipated outputs of the meeting are: 1) develop a team who will share emerging practices in tele-rehabilitation that will be made publicly available 2) generate a consensus report on gaps and future directions in telerehabilitation and 3) develop priority research questions for a future grant application. This meeting will allow us to develop a research agenda based on available evidence and expert opinion to improve delivery of telerehabilitation in SOT patients. ",2022,2023,University Health Network,15333.01,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,Health Systems Research,Health service delivery,2022 +C20700,202203PJT,Promoting Outdoor Mobility via Enhancing Neighborhood Walkability for Racialized Older Women: A Community-Based Participatory Project.,"The COVID-19 pandemic amplified the vulnerability of older adults due to health risks, increased isolation, and difficulties accessing essential services. Racialized older women from Muslim communities have been at increased risk for deterioration in health status during the pandemic. This is directly related to increased incidences of violence against women of color and religious minorities which has translated into increased isolation and restricted mobility outside the home. We will use participatory and mixed method approaches to engage racialized immigrant older Muslim women in identifying barriers to walking outdoors in their local neighborhoods. We will then co-design and implement strategies to maximize opportunities for outdoor walking. Final study outcomes will include an intersectional analysis of barriers and facilitators of outdoor walking in this population and tailored recommendations for improving outdoor mobility. ",2022,2026,University of Alberta,306306,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Women | Minority communities unspecified | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Social impacts,2022 +C20701,202203AWE,Prize 202203PJT - Promoting Outdoor Mobility via Enhancing Neighborhood Walkability for Racialized Older Women: A Community-Based Participatory Project.,"The COVID-19 pandemic amplified the vulnerability of older adults due to health risks, increased isolation, and difficulties accessing essential services. Racialized older women from Muslim communities have been at increased risk for deterioration in health status during the pandemic. This is directly related to increased incidences of violence against women of color and religious minorities which has translated into increased isolation and restricted mobility outside the home. We will use participatory and mixed method approaches to engage racialized immigrant older Muslim women in identifying barriers to walking outdoors in their local neighborhoods. We will then co-design and implement strategies to maximize opportunities for outdoor walking. Final study outcomes will include an intersectional analysis of barriers and facilitators of outdoor walking in this population and tailored recommendations for improving outdoor mobility.",2022,2023,University of Alberta,38500,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2022 +C20702,202203ECP,Prize 202203PJT: The Youth Development Instrument: engaging stakeholders and linking data to monitor and promote youth mental health and well-being trajectories beyond the pandemic,"Mental disorders have a peak onset in adolescence and young adulthood, with 1 in 5 Canadians under the age of 25 affected per year. Along with social and economic stressors such as discrimination and income inequality, youth face unique impacts caused by the climate crisis and the COVID-19 pandemic. Social and emotional learning and positive childhood experiences can avert or delay mental illness onset and/or severity, yet 95% of health system funding is allocated to specialized, hospital-based or downstream services. Through intersectoral collaborations, we developed the Youth Development Instrument (YDI) to measure youth mental health (MH) and well-being and to investigate how childhood experiences influence MH and well-being trajectories in emerging adulthood. Developed to measure MH and well-being of Grade 11 students, the YDI was first piloted in Spring 2021. Wave 1 collected ~2,300 responses in 6 school districts in British Columbia (BC). By the end of Wave 2 (Spring 2022), we anticipate collecting 10,000 responses from 22 BC districts. Our project aims to: 1) Monitor pandemic-era youth MH and well-being using the YDI; 2) Identify early life risk and protective factors of internalizing and externalizing MH outcomes and life satisfaction in youth in the context of the COVID-19 pandemic; and 3) Inform the development of a collaborative data-to-action strategy to support school, community, and health system stakeholders in improving youth MH and well-being during COVID-19 recovery using Aim 1 and 2 findings. Mental disorders pose a critical threat to young people's current and future health. Early intervention may prevent a substantial portion of this burden but requires an understanding of the complex web of its determinants. We will link the YDI to other data sources to create a comprehensive map of the links between child and youth development and MH in emerging adulthood, in turn informing data-to-action initiatives",2022,2023,Simon Fraser University,148176.49,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20703,202203ECP,Prize 202203PJT - The test-negative design for the estimation of COVID-19 vaccine effectiveness: design evaluation and development of statistical methods in the evolving context,"Fast research designs have been proposed for estimating how well different vaccines protect against disease, severe disease, hospitalization, and death from COVID-19. In fact, ongoing study is needed to evaluate different levels of vaccination (2 doses, boosters, different lags between doses, etc) in terms of how well they protect against illness, which may vary depending on the current circulation of virus variants. These fast designs typically involve identifying people who have been tested for COVID-19, often at a test-site or in a hospital. An established design is called the ""test-negative design"" which specifically involves identifying people who have symptoms associated with the disease in question and who then get tested. Scientists can estimate vaccine effectiveness by comparing people who test positive to people who test negative. If the negatives have higher rates of vaccination, this will indicate effectiveness of the vaccine. But, depending on how the design and statistical methods are applied, there may be bias in the estimation of effectiveness. Our research team has recently noted that, because of challenges of how test data are collected in our healthcare systems across Canada, the classical version of the test-negative design cannot always be applied. For example, some designs have used all test data, rather than only data from those who have certain symptoms. We are interested in evaluating how much bias can be caused by this difference in design, and identifying scenarios in which this can create misleading results. Secondly, we are interested in developing statistical methods that can address the limitations of the regression approach that is essentially the only one currently being used. We will identify limitations of current methods and propose new (or adapted) methods that can address these limitations. Our goal is to produce more reliable statistical methods so that we can improve our monitoring of the benefits of vaccination. ",2022,2023,Université de Montréal,112343,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,"Vaccines research, development and implementation",,2022 +C20704,202205REC,COVID-19 Recommendations and Contextualization (eCOVID19RecMap) Extension,"The specific objective(s) of this funding opportunity are to continue to: Accelerate the knowledge mobilization of high-quality and real-time evidence and/or solutions that responds to an identified evidence need(s) to support Canada's ongoing response to the pandemic in order to better prevent, detect, treat and manage COVID-19; and Generate evidence related to one or more diverse population(s), by addressing, for instance: health equity considerations, health status (e.g. high risk populations, individuals with comorbid conditions), sex and gender, a life cycle approach (from children to aging adults), and/or the needs of racialized or First Nations, Inuit, Metis and Urban Indigenous populations to equitably improve health outcomes across the lifecycle.",2022,2023,McMaster University,769987.68,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Research to inform ethical issues,"Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2022 +C20706,202202PCS,Indoor air quality and the COVID-19 pandemic: using interdisciplinary knowledge translation to reduce transmission of respiratory disease and improve indoor air quality in diverse community spaces in Toronto,"Indoor air quality (IAQ) in community congregate settings, including homeless shelters, drop-in centres, and group homes, has historically been largely ignored by public health authorities. The COVID-19 pandemic has compounded this issue, as poor IAQ can result in increased transmission. In addition, public health authorities in Ontario have not provided congregate settings with evidence-based COVID-19 IAQ guidance. The current situation has further exacerbated existing disparities and forced users, workers, and operators to make difficult decisions between receiving/providing essential services and increased risk of infection. The proposed effort addresses the lack of guidance by bringing together a multidisciplinary team of researchers and knowledge translators in partnership with a variety of agencies and individuals that operate and work in community congregate settings. Together, we will build pandemic preparedness and response capacity in the community setting in Toronto through the provision of accessible and practical IAQ guidance to reduce exposure and mitigate transmission. This guidance will address the diversity of buildings and services in the community setting, while taking into account the diversity of perspectives and power dynamics that occur across sectors and in facilities. Specific activities include developing a series of webinars; preparing evidence-based plain language IAQ guidance; authoring high-impact interdisciplinary opinion/editorial articles; training of highly qualified personnel to develop and share IAQ COVID-19 mitigation measures, and the development of a research proposal to address gaps in the evaluation, impact, and implementation of mitigation strategies. Through the process of bringing multidisciplinary researchers, community organizations and workers together, we will build a robust interdisciplinary community of research and practice to address IAQ pandemic preparedness and response in these essential spaces. ",2022,2023,University of Toronto,19250,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +C20707,202202PCS,Engaging Stakeholders and Planning for the Implementation of Virtual Care Competencies within Mental Health Care,"The COVID-19 pandemic catalyzed a rapid transition to virtual care across Canada. However, research indicates that health care providers often felt under-prepared to make the transition to virtual practice. As virtual care becomes a mainstay of practice, there is an urgent need to develop education and training resources to ensure a workforce that is both confident and competent to provide mental health care virtually. Preliminary results indicate that efforts are underway to develop discipline-specific virtual care competencies. However, there is a lack of consensus on the virtual mental health care competencies required for interprofessional care teams. Moreover, virtual care competency frameworks rarely address the transdisciplinary training needs of professionals working in mental health contexts. As a result, our project objectives are twofold: The first goal (1) is to disseminate our virtual mental health competency framework, designed collaboratively with health professionals in mental health contexts. The second goal (2) is to leverage stakeholder input to plan for the implementation of the virtual mental health competency framework in health professions education and curriculum support. The competency framework emerging from this grant will serve as the foundation for future development and expansion of virtual care curriculum modules and virtual learning resources to further support virtual mental health care capacity building across Canada. ",2022,2023,Centre for Addiction and Mental Health (Toronto),7700,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Digital Health,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C20708,202202PCS,Bioinformatics School: Building a Skilled Workforce in Infectious Disease Epidemiology,"More critical now given the COVID-19 global pandemic, bioinformatics skills are urgently needed to support rapid translation of infectious disease research to improve healthcare and decision making. This need is further compounded by the surge in genomic and epidemiological data being generated globally by researchers. Public health infectious disease researchers and practitioners are increasingly seeking computational skills to aid their analysis, comprehension and research translation activities. However, acquiring this level of topic specific and advanced bioinformatics knowledge and skills is challenging because adequate training programs are scarce. The Canadian Bioinformatics Workshops proposal herein seeks CIHR funding to redevelop its 'Infectious Disease Epidemiology' workshop and to provide accessible training opportunities to Canadians for immediate skill development in the cutting-edge bioinformatics resources and tools necessary for pathogen research. The updated 'Infectious Disease Epidemiology' workshop will be an intensive 4-day, virtual hands-on workshop designed to guide researchers through the key bioinformatics concepts and tools required to analyze pathogen genomic data sets and integrate epidemiological data. Participants will gain practical experience and skills to be able to: 1) understand next generation sequencing (NGS) platforms as applied to pathogen genomics and metagenomics sequencing; 2) analyze NGS data for pathogen surveillance and outbreak investigations; 3) identify and analyze antimicrobial resistance genes; 4) detect emerging pathogens from metagenomics datasets; 5) perform phylodynamic analysis on these datasets; and 6) use visualization tools for genomic epidemiology analysis. Becoming proficient in these computational skills not only has direct and immediate impact on current public health pandemic efforts, but also engages and accelerates new infectious disease research for the long-term benefit of public health in Canada.",2022,2023,"Ontario Institute for Cancer Research (Toronto, Ontario)",38500,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Data Management and Data Sharing,,,Canada,Canada,Epidemiological studies,,2022 +C20709,202202PCS,Pandemic and Health Emergency Management in Long-Term Care: Gathering Insights from Recent Events to Inform Future Planning in British Columbia,"Residents in long-term care homes in Canada are vulnerable to health emergencies, such as pandemics and natural disasters. This was shown during the first wave of the COVID-19 pandemic, which resulted in many deaths of residents in care homes due to COVID-19. When disaster strikes, residents in long-term care are among the most vulnerable in society. Residents in long-term care have complex medical and social care needs related to dementia, frailty, high risk of falls, reduced mobility, language barriers, and multiple chronic illnesses among other needs. These complex needs place long-term care residents at great risk during health emergencies. For example, residents that need to be moved from their long-term care home to another site have a high chance of dying. This proposed planning project will explore the recent series of major health emergencies of British Columbia in 2021, including: 1) extreme heat resulting in many deaths, 2) wildfires and related evacuations and poor air quality, 3) widespread flooding resulting in mass evacuations, and 4) ongoing COVID-19 pandemic related management. The planning activities will include a review of recent reports from British Columbia and evidence on health emergency management in long-term care. Also, one-on-one conversations with key informants and group dialogue with the key informants and relevant stakeholders will be held to learn from their experiences. These activities will help to build a network of research collaborators across BC interested in studying pandemic and health emergency management. Also, meaningful research questions and objectives will be identified to inform the planning of a larger study. This proposed planning project and the future research stemming from this will contribute to improve long-term care homes' preparedness for health emergencies and thus ensure better continuity of care to protect the health and well-being of long-term care residents.",2022,2023,"Fraser Health Authority (Surrey, BC)",19250,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2022 +C20710,202203PJT,Microvascular Endothelial Loss and Regeneration in Acute Lung Injury,"The efficient uptake of oxygen by the lung is dependent on maintaining a thin but highly efficient barrier between the air spaces and the blood. This barrier is comprised of a thin layer of endothelial cells (the inner lining of blood vessels) and epithelial cells (cells that line the airways). Viral (i.e., COVID-19 or influenza) or bacterial infection can damage this fragile barrier, resulting in flooding of the air sacs and severe inflammation, preventing oxygen from reaching the blood. This is called acute respiratory distress syndrome (or ARDS) and these critically ill patients often require mechanical ventilation and have high death rates. We have shown that selective damage to the lung endothelial cells reproduces many of the characteristics of ARDS. However, we have also shown that the lung has an amazing capacity to regenerate and repair blood vessels and recover its ability to exchange oxygen. Using new technologies that allow us to look at which genes are active in each individual cell of the entire lung (single-cell transcriptomics), we have identified novel stem- and progenitor-like endothelial cell populations that orchestrate the regeneration of damaged endothelial cells and the repair of the small blood vessels that surround the air sacs, thereby allowing the lung to recover its ability to provide oxygen to the body efficiently. We will study the relevance of these novel stem and progenitor populations for resolution of severe lung injury in clinically relevant animal models of ARDS with particular attention to the influence of biological sex (male or female) and advancing age, which are known risk factors for poor outcomes in this disease. We will also develop and test novel therapies designed to enhance lung endothelial cell regeneration and small blood vessel repair in preclinical models of ARDS, which may provide new tools that can improve survival of critically ill patients such as those with COVID-19. ",2022,2027,Ottawa Hospital Research Institute,907137,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2022 +C20711,202207TAA,"Working apart and together, across and between: lessons learned from an Indigenous and non-Indigenous organizational partnership in Indigenous harm reduction research during the COVID-19 pandemic",,2022,2023,Direct Payment,2310,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +C20712,202202PCS,"COVID-19 vaccine awareness in British Columbia: A community-based knowledge dissemination initiative for people who are pregnant, breastfeeding, and parents to young children","Limited data on COVID-19 vaccine efficacy, acceptance, and uptake for children and for people who are pregnant or breastfeeding may contribute to vaccine hesitancy in Canada. Considering that vaccine acceptance varies greatly based on knowledge, cultural beliefs, community COVID-19 transmission, and health and community services, it is important to address vaccine confidence and develop locally-relevant interventions that are tailored to community needs. Building on our team's current work to identify and explore COVID-19 vaccine perceptions and concerns among these target groups, the goal of this project is to use a community-based approach to improve COVID-19 vaccine awareness during pregnancy, breastfeeding, and parenthood in BC. In partnership with Interior Health and several community organizations (The Bridge, KCR, PIRS, and MOSAIC), our collaborative team will: (1) engage with equity-deserving community members to explore their needs for targeted COVID-19 vaccine communication; (2) co-design a knowledge mobilization toolkit (e.g. website, infographics, videos, posters) to promote COVID-19 vaccine awareness specific to these communities; and (3) develop, implement, and evaluate a knowledge mobilization strategy to disseminate the toolkit to these target populations in BC. By using community-based approaches to address contextual barriers to vaccination, this study will provide tailored resources for these priority populations to promote COVID-19 vaccine confidence and awareness. ",2022,2023,University of British Columbia,15400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2022 +C20713,202203PJT,Symptom-TArgeted Rehabilitation for Cognitive Complaints after COVID (STAR-C3),"We now know that up to 40% of adults with COVID are still having cognitive problems months later, including ""brain fog"", mental fatigue, memory impairments, and difficulty with everyday tasks like following a conversation. People report these problems affect their ability to do things like return to work. We know ""Long COVID"" can cause long-lasting cognitive problems, but we don't know how best to treat them. One source of guidance for helping patients with Long COVID is research on a group with similar challenges: adults with traumatic brain injury (TBI), especially those with mild TBI or concussion. Adults with mild TBI have many of the same cognitive problems as those with Long COVID. Best practices in mild TBI rehabilitation should apply equally well to Long COVID, because they are best practices for all patients with cognitive challenges: treatments must be tailored to the person and their needs, focused on solving everyday thinking challenges rather than 'fixing' deficits, and given in a relatively high dose. As a first step, we will conduct a pilot randomized clinical trial of a mild TBI rehabilitation method called Symptom-Targeted Rehabilitation (STAR), which we have adapted for adults with post-COVID cognitive challenges. At present, most adults with these challenges receive no rehabilitation, and therefore we will randomize participants to either the STAR intervention or current standard care, which is receiving general information about how to manage cognitive challenges. Participants will be 100 adults with Long COVID. Our main outcomes will be feasibility of recruitment, adherence to intervention, and participants and therapists ratings of the feasibility, appropriateness, and acceptability of the STAR methods. These results will prepare us for the next step: a multi-centre, international study to test the effectiveness of STAR for adults with Long COVID. ",2022,2023,McMaster University,184814.63,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase)",2022 +C20714,202202PCS,Leveling the Playing Field: Translating Physical Activity Knowledge and Messaging for Equity-Deserving Groups,"Participating in recommended levels of physical activity is linked to many positive health benefits in children and youth. Unfortunately, the COVID-19 pandemic has negatively impacted the physical activity and sedentary behaviours of this young population. Worst still, children and youth from equity deserving groups (e.g., particular groups or communities that identify barriers to participating in society such as, girls, newcomers to Canada, and children with disabilities) were unevenly impacted by COVID-19 in terms of physical activity and sport participation, access, and opportunities.While what we know about children's physical activity levels continues to grow, less is known about how this knowledge is shared with public health professionals and community stakeholders best positioned to do something with the findings; and this is particularly true among equity-deserving groups. Team efforts are required to ensure materials are tailored and customized to equity-deserving groups to maximize impact. As such, this grant aims to organize a group of national experts, stakeholders (including individuals with lived experiences), and marketing and communications specialists to develop a suite of materials and products that can be used to help share key findings from the 2022 ParticipACTION Report Card on Physical Activity for Children and Youth and provide tips and tricks for encouraging and supporting healthy behaviours in children, including equity-deserving groups. This grant provides an opportunity for a timely and unique collaboration between research, public health, and health marketing/communication experts, in collaboration with community stakeholders, to improve physical activity among children and youth in Canada, with the focused inclusion and application of an Equity, Diversity, and Inclusion (EDI) lens. The proposed activities will amplify the impact of the 2022 ParticipACTION Report Card to stakeholders and members of equity-deserving groups. ",2022,2023,Western University,7700,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Communication | Indirect health impacts,2022 +C20715,202202PCS,Dissemination activities to support the uptake of sex and gender recommendations into dementia research to guide equitable interventions and policies,"The COVID-19 pandemic has highlighted the importance of planning more equitable care, especially for vulnerable population such as persons with dementia and their care partners. Developing evidence-based and actionable recommendations that address sex and gender differences and needs, along with race, socioeconomic status, and geographical location, is paramount to equitable care. However, it is not well understood how to develop recommendations that consider sex and gender, especially when engaging persons with lived and/or clinical experience of dementia. Learning how global dementia strategies have taken sex and gender into account is the first step and leveraging our network to share with broader audiences (patients, care partners, clinicians, and healthcare managers) how we developed recommendations that consider sex and gender is the second step. To encourage a broad practice of developing sex and gender recommendations for equitable care in research, clinical practice, and health policies, we will conduct the following four activities: 1) a rapid review on how global dementia strategies have considered sex and gender; 2) infographics that present how sex and gender influence healthcare service use and satisfaction in four Canadian provinces; 3) a manuscript and national and international presentations on our approach and lesson learned on how we developed equitable recommendations for dementia care; 4) a webinar to teach how to include sex and gender in evaluation for policy and practice and in developing equitable recommendations. These activities aim to improve the consideration of sex and gender in healthcare research, to guide equitable policy and practice for persons with dementia and care partners and ultimately to ensure that men and women with dementia both receive equitable and high quality of care.",2022,2023,CIUSSS de Centre-Ouest-de-l'Ile-de-Montreal Hopital general juif Jewish General Hospital,15400,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Gender,,,Canada,Canada,Health Systems Research,Health service delivery,2022 +C20716,202203OBH,Network for Canadian Oral Health Research,"Oral health is a major contributor to the overall health and well-being of Canadians. Poor nutrition can result from tooth loss and decay, and a number of oral health ailments can seriously reduce one's overall health or worsen pre-existing conditions. This includes oral cancer, chronic orofacial pain, pulpitis (inflammation), or periodontitis (infection), among other conditions. The ongoing COVID-19 pandemic has shed light on factors that lead to disparities in oral health outcomes and access to preventative care, such as socioeconomic status, race, ethnicity, and disability. For nearly a decade, the Network for Canadian Oral Health Research (NCOHR) has proven its ability to initiate, support, and advance collaborative oral health research across the population. With a well-established infrastructure in place, the NCOHR is ready to advance oral health research and knowledge translation even further. Working together with scientists, healthcare providers, industry partners, government agents, and patients and communities, the NCOHR aims to spearhead new discoveries and strengthen existing models as they relate to the improvement and maintenance of good oral health. The NCOHR promotes excellence in oral health by training the next generation of researchers and clinicians with a strong dedication to diversity, equity, and inclusion. As we improve the oral health of Canadians, we progress the global health of all. ",2022,2027,CIUSSS de Centre-Ouest-de-l'Ile-de-Montreal Jewish General Hospital,231000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Health Systems Research,Health service delivery,2022 +C20717,202203PJT,"The First Nations Wellness Initiative (FNWI): Strengthening, Expanding and Sharing Community-Driven Approaches","Many First Nation peoples and communities are disproportionately affected by mental health and substance use challenges due to the enduring harmful effects of colonialism. The COVID-19 pandemic is exacerbating these challenges, alongside re-traumatization due to the unmarked mass graves at residential schools found across Canada. Mental health services often fail to foster meaningful and active involvement from community members in service planning, with community members having little or no involvement in the decision-making process. There is an urgent need for innovative community-driven initiatives grounded in local contexts and culturally specific Indigenous practices, priorities, and knowledges. The First Nations Wellness Initiative (FNWI) is a successful collaborative model for developing community-driven, evidence-informed and community-based wellness strategies in First Nations. It involves local data collection and participatory action research to develop wellness strategies in each participating community. Through a previously funded COVID-19 Mental Health & Substance Use Service Needs/Delivery Operating Grant, the FNWI aimed to mitigate the impacts of the pandemic in two First Nations by implementing and enhancing the FNWI. In the current application, we propose to strengthen, expand and share successful community-driven approaches. Our objectives are to: 1) implement all phases of the FNWI model as part of a new partnership with Wiikwemkoong Unceded Territory to establish a community-driven wellness strategy that is tailored to their needs and builds on community strengths; 2) continue supporting community wellness planning in Walpole Island First Nation and Saugeen First Nation, including further developing and evaluating their wellness strategies; and 3) engage in extensive knowledge translation and mobilization activities within and across communities, including sharing best practices, tools, and products. ",2022,2026,Centre for Addiction and Mental Health (Toronto),1599271.52,Human Populations,Other,Unspecified,Other,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2022 +C20719,202203PJT,Retaining and Attracting Workers in Long-Term Care Homes: How System Dynamics Can Help,"The COVID-19 pandemic has made clear the dire need to address underlying long-term care (LTC) workforce and workplace issues that affect resident quality of care and quality of life. These issues include insufficient funding, under-staffing, poor working conditions, complacency towards overburdened and undervalued staff, and lack of regulatory enforcement. These issues also contribute to poor job satisfaction among workers. In recent years, there have been policy changes to improve workforce and workplace conditions. But, some of these 'fixes' were later shown to be ineffective or even made the problem worse. These 'fixes that fail' are not an uncommon occurrence in complex systems like healthcare. The interconnectedness of factors, the nonlinearity of relationships (can't draw a straight line between two variables), the feedback processes created in response to policy changes, and delayed reactions all make for a complex system that common quantitative tools used in policy design and evaluation, such as spreadsheet models and regression analysis, have difficulty handling. The proposed research uses novel engineering approaches, including group model building, to create a dynamic model of LTC job satisfaction. Our proposed model relies on quantitative and qualitative data available only from LTC homes. We also rely on the expertise of personal support workers to help specify causal relationships between variables. We will test how well the model replicates historical data from a LTC home. We will then use the model to test 'what if' policy scenarios. Policy makers can graphically see how outcomes, like job satisfaction, might respond over time to hypothetical policies. They can also trace the causal pathway between policy and outcome to better understand which variables have most impact. While real world interventions are needed, the proposed research can be a first step to designing and improving the LTC system. ",2022,2024,York University,173770.52,Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +C20720,202202PCS,Strengthening Toronto's response to violence against women: advancing an academic-community partnership to plan and mobilize an evidence-informed agenda,"The COVID-19 pandemic has worsened social problems in Canadian cities, including violence against women, with significant negative consequences for women's health. Organizations that support women experiencing violence have had to rapidly adapt their programming to address these emergency conditions. As a team of academics, violence against women service providers, advocates, and women with lived experience of violence, we conducted a study in Toronto that produced important findings around how services can be improved to better respond to the changing and diverse needs of women facing violence. We aim to now share our findings with key stakeholders throughout the city and plan next steps for research and policy that strengthen Toronto's response to violence against women during and beyond the COVID-19 pandemic. In particular, this project has three objectives. First, we will strengthen and expand our existing intersectoral partnership in Toronto, including with funders of violence against women organizations, city housing and shelter representatives, private landlords, public health professionals, newcomer support services, and social assistance programs. Second, we will create snapshots of our Toronto study findings (such as infographics, policy briefs, and presentations) to facilitate engagement with these intersectoral actors and set a research and policy agenda for violence against women in Toronto. Finally, we will plan the next steps for our partnership, including policy recommendations, implementation of best practices, and evaluating interventions to prevent and respond to violence against women. Our goal is to improve the supports available to women experiencing violence in Toronto. ",2022,2023,Dalhousie University,15376.9,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts,2022 +C20721,202202PCS,Engaging Community Stakeholders to Address Vaccine Hesitancy in Racialized and Diasporic Communities,"Evidence shows that COVID-19 vaccines in Canada reduce infection, lower transmission, and strongly prevent severe outcomes and hospitalizations. Vaccines are an important part of a layered approach to reducing severe illnesses and death. Yet there are still pockets of people hesitant to get vaccinated, In Canada, millions of people are still not vaccinated, including people come from different ethno-racial communities. Little is known about the reasons for vaccine hesitancy in these communities. Preliminary findings from our scoping review reveal lack of easy access to vaccines, poverty, a mistrust of public institutions, racism, and mis/disinformation as major causes. As a result, the goal of this planning and dissemination project is to build equitable and empowering partnerships to address vaccine hesitancy in ethno-racial communities in the Greater Toronto Area (GTA). We aim to bring together community leaders, service providers, and key informants from Asian, Black, Middle Eastern, Latinx, and North African (MENA) communities to: (i) share the results of a recent literature review on vaccine hesitancy in the above communities; (ii) engage community stakeholders in discussing the reasons for vaccine hesitancy in the their communities; (iii) work with these community stakeholders on good public health messaging around vaccine hesitancy and misinformation; and (iv) develop a community-based CIHR grant proposal team that works toward a grassroots public health communication plan for use during public health crises. ",2022,2023,Ryerson University,19221.51,Human Populations,Asian | Black | Other,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2022 +C20722,Unknown,Acute Respiratory Mortality Surveillance (ARMS) for Coronavirus Infection (COVID-19): A globally relevant technology to strengthen mortality surveillance for acute respiratory deaths in many countries lacking complete medical certification of death,"The current global infectious threat, COVID-19, has not yet been widely detected in sub-Saharan Africa or other low income countries in Asia. It is almost inevitable that it will reach those places. While unusual spikes in infection-related deaths can register quickly in higher income countries and in China, they can go unrecognized for weeks or months in low-income settings where even very ill people do not go to a hospital, infecting others. Detecting a mortality signal is important and may be the first step in recognizing a serious outbreak. We propose to build on our extensive experience using verbal autopsy (VA) in the long-running Indian Million Death Study, and ongoing studies in China, Hong Kong, Ethiopia and Sierra Leone to develop an enhanced verbal autopsy module to identify deaths from COVID-19. This will serve as a model for the next novel pathogen-as near as possible to real time in settings without routine medical certification of death. We will test three hypotheses: #1 An ""Acute Respiratory Mortality Surveillance"" (ARMS) module can be added quickly to the WHO VA instrument and validated against hospitalized cases and deaths (paired with epidemiological information and machine learning) to distinguish COVID-19 from other causes of respiratory deaths. #2 Early deployment of ARMS in China, Hong Kong, India, Sierra Leone, and Ethiopia will help establish baseline distributions of usual acute respiratory deaths, as a comparator for COVID-19 deaths, and to inform modelling. #3 Effective knowledge translation of an open-source, widely-available ARMS module will improve the global response to COVID-19, particularly in the lowest income countries and help to improve mortality assessments for any subsequent COVID-19 waves. A successful ARMS will contribute to stopping the current outbreak and add novel surveillance tools. All materials and results will be made available globally to ensure the broadest use.",2020,-99,Unity Health Toronto,717240,Other,Unspecified,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Africa | Americas | South-East Asia | Western Pacific,,,,Canada,Canada | China | Hong Kong | India | Sierra Leone | Ethiopia,Epidemiological studies,Disease surveillance & mapping,2020 +C20723,Unknown,Assessing and Mitigating the Food Security Consequences of COVID-19 in China,"This project will evaluate the impacts of the COVID-19 outbreak on household food security in Chinese cities, assess the effectiveness of temporary policies from multi-stakeholder perspective and develop social and policy measures to mitigate the impacts. Building on the expertise, research instruments, and networks developed through the SSHRC-funded Hungry Cities Partnership, our objectives are to: 1) Investigate the immediate food security challenges resulting from China's quarantine measures, unstable food supply, and fear of food shopping in two COVID-19 affected cities (Wuhan and Nanjing); 2) Compare food security status in Nanjing following the COVID-19 outbreak with baseline data collected through Hungry Cities in 2015; and 3) Synthesize and assess policies established to address food security challenges and promote effective measures by engaging local stakeholders. Our Canadian-Chinese research team has strong multidisciplinary expertise in food security evaluation, food policy analysis and the social and food security impacts of infectious diseases. Using a mixed-methods approach, we will generate rapid answers to Objective 1 through an online household survey and follow-up telephone interviews with residents of Wuhan and Nanjing, and a complementary inventory of immediate policy measures. Building on the survey instruments and established connections developed through the Hungry Cities Partnership, we will address Objective 2 through a longitudinal analysis to evaluate changes in household food security before and after the COVID-19 epidemic. Objective 3 will be addressed through a policy analysis and in-depth interviews with diverse local stakeholders. Outcomes will be relevant to academics, international organizations, and policymakers involved in efforts to strengthen food provisioning amid the epidemic in China. Results will also be useful to policymakers in other countries at risk of food security during infection disease outbreaks.",2020,-99,Wilfrid Laurier University,328680.75,Human Populations | Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Western Pacific,Western Pacific,,,,China,China,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +C20724,Unknown,Canada's response to Covid-19 in the context of the IHR(2005) and its opportunity to lead in global health security: a policy analysis,"On January 30th, 2020 the World Health Organization (WHO) declared the outbreak of a novel coronavirus originating in the city of Wuhan, China an international health emergency. Guided by global rules (the International Health Regulations), the WHO has taken action to limit the harm caused by the virus while at the same time protecting the international travel and trade. This grant will determine how Canada has adhered to these global rules and what it can do to support them. We will review stories from the media, important policy documents and other relevant materials. We will also interview key people in Canada and around the world involved in protecting the public from these threats. We will specifically examine if there is an opportunity for Canada to help lead efforts to protect the world from similar threats in the future.",2020,-99,Bruyère Research Institute,159297.75,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20725,Unknown,COVID-19 Evidence Network to support Decision-making (COVID-END),"The science about how to prevent and manage COVID-19 and its spill-over effects on society is changing rapidly. Summaries of the best available science (which we call evidence syntheses) are the best place to turn when making decisions about public-health measures (e.g., wearing masks), clinical management (e.g., prescribing drugs), health-system arrangements (e.g., making the most of virtual doctor visits), and economic and social responses (e.g., adjusting schools and workplaces). COVID-END will bring together: 1) 25+ Canadian evidence-synthesis teams; 2) leaders of key Canadian initiatives that support the use of science by citizens, service providers and policymakers; 3) diverse citizen partners from across Canada; 4) Canadian professional bodies; and 5) policymakers and leaders from Canadian governments and health authorities. COVID-END will: 1)prepare and update evidence syntheses at the request of Canadian decision-makers in timelines ranging from 4 hours to 10 days; 2)maintain an inventory of the best evidence syntheses for COVID-19 decisions to ensure that Canadian decision-makers have available at all times the most updated summarized science; 3)work with Canadian decision-makers to ensure that their most urgent questions are prioritized and responded to by the most appropriate team in a timely way and that these decision-makers have the capacity to find and use the available science in their decision-making; 4)keep alert to emerging issues where evidence syntheses may be needed in the future; and 5)work with Canadian and global partners to reduce duplication and enhance coordination in the evidence response to COVID-19. COVID-END will undertake (or co-create) its work in close partnership with citizens and with the decision-makers who pose questions and whose existing processes we need to intersect with. COVID-END will disseminate and support the use of its work both directly and through many existing initiatives.",2020,-99,McMaster University,750000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C20726,Unknown,COVID-19 Evidence Network to support Decision-making (COVID-END) - Extension,"The science about how to prevent and manage COVID-19 and its spill-over effects on society is changing rapidly. Summaries of the best available science (which we call evidence syntheses) are the best place to turn when making decisions about public-health measures (e.g., wearing masks), clinical management (e.g., prescribing drugs), health-system arrangements (e.g., making the most of virtual doctor visits), and economic and social responses (e.g., adjusting schools and workplaces). COVID-END will bring together: 1) 25+ Canadian evidence-synthesis teams; 2) leaders of key Canadian initiatives that support the use of science by citizens, service providers and policymakers; 3) diverse citizen partners from across Canada; 4) Canadian professional bodies; and 5) policymakers and leaders from Canadian governments and health authorities. COVID-END will: 1)prepare and update evidence syntheses at the request of Canadian decision-makers in timelines ranging from 4 hours to 10 days; 2)maintain an inventory of the best evidence syntheses for COVID-19 decisions to ensure that Canadian decision-makers have available at all times the most updated summarized science; 3)work with Canadian decision-makers to ensure that their most urgent questions are prioritized and responded to by the most appropriate team in a timely way and that these decision-makers have the capacity to find and use the available science in their decision-making; 4)keep alert to emerging issues where evidence syntheses may be needed in the future; and 5)work with Canadian and global partners to reduce duplication and enhance coordination in the evidence response to COVID-19. COVID-END will undertake (or co-create) its work in close partnership with citizens and with the decision-makers who pose questions and whose existing processes we need to intersect with. COVID-END will disseminate and support the use of its work both directly and through many existing initiatives.",2021,-99,McMaster University,825000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +C20727,Unknown,Developing COVID-19 Risk Communication and Community Engagement Readiness Strategy Guidance for Travelers Visiting Friends and Relatives (VFR),"Containing an emerging disease, such as the 2019 novel coronavirus (COVID-19) depends on stopping the spread of the disease to other areas around the world. People who travel back to their countries of origin to visit friends and relatives (VFR) (including the children of immigrants and international students) are often at a higher risk of getting the disease and then spreading it to others. A better understanding of VFR traveler knowledge, risk perceptions, information needs, barriers to pre-travel care and advice, and access to protective measures will help us better develop strategies to keep travelers healthy. This will prevent the spread of COVID-19 and its potential negative consequences. Our research will take place in the Fraser Valley and lower mainland of British Columbia as an area with a high number of immigrants. We are seeking information from Chinese and Punjabi VFR travelers, international students at the University of the Fraser Valley, and family physicians. We will use a combination of focus groups, surveys and interviews to get this information. The researchers for this study have a lot of experience in working with immigrant populations on infectious diseases to determine their risk communication needs. This includes research with VFR travelers. The University of the Fraser Valley has partnerships with organizations (such as the Divisions of Family Practice and Community Services) that enable us to easily access research participants. They will also help us access their large and diverse international student body. Including researchers from other countries, like Australia and New Zealand, will help us make sure our research and recommendations can be part of a coordinated international response. Our research also includes senior people in the BC provincial health system to make sure our results can be quickly used in practice.",2020,-99,University of the Fraser Valley,205483.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication,2020 +C20728,Unknown,Ethical Pathways for Therapeutics and Vaccine R&D in the Context of Public Health Emergencies of International Concern: An Analysis of the 2013-16 Ebola Outbreak to Rapidly Inform COVID-19 R&D,"A cross-cutting research priority identified by the recent WHO COVID-19 Global Research and Innovation Forum is the establishment of appropriate ethical oversight and global collaboration to accelerate COVID-19 R&D, and to establish these in such a way that promotes solidarity and equity. Yet, the existing COVID-19 research roadmap and WHO R&D Blueprint are largely silent on the global ethical pathways required to guide and oversee rapid therapeutics and vaccine R&D in this context (including whether and how such pathways ought to be modified, or precisely what solidarity and equity require for these activities). To identify and successfully navigate these ethical and regulatory pathways for COVID-19 R&D, we can look to the unprecedented R&D response to the 2013-16 Ebola virus disease (EVD) outbreak for guidance. Only five months following the development of the first study protocols for EVD, the first patients were enrolled in clinical trials. Only four years later, the first vaccine was licensed in the United States. The atypical expediency of these R&D efforts was, in part, a product of significant modifications and adaptations to the usual ethical and regulatory pathways for health product development-pathways that involve ethical inputs into study protocols, independent ethics review of studies, global consultation and governance, data sharing agreements, and the approval, licensure, and dissemination of resulting products. This project will for the first time (1) analyze and describe the ethical pathways for R&D that existed or were established for EVD in order to aid the global research community in navigating these pathways for COVID-19 R&D; (2) analyze and describe the ethical pathways as they are established and navigated for COVID-19 R&D in order to rapidly support ongoing and future COVID-19 R&D; and (3) compare and conduct an ethical analysis of the ethical pathways for EVD and COVID-19 R&D to inform future R&D during epidemics.",2020,-99,Western University,212742,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Ebola virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Research to inform ethical issues,Research to inform ethical issues in Research,2020 +C20729,Unknown,Harnessing human mobility and surveillance data for disease forecasting to drive evidence-based public health policy during the COVID-19 epidemic,"COVID-19 emerged from Wuhan, China in late December 2019 and is currently spreading to international destinations, globally. At the time of writing, cases have been confirmed in 24 countries worldwide. Of major concern are early indications of human-to-human transmission outside of China in those without a travel history to China. During the two months of this epidemic, public health policy has adapted rapidly to emerging information about disease location, disease burden, and clinical features of COVID-19. Public health screening and interventions will need to continuously evolve over the course of this epidemic to keep up with new foci of infection and potential new regions of COVID-19 exportation. We aim to harness validated tools to predict where COVID-19 will spread in real time by using a novel, AI-driven web-based surveillance tool coupled with real-time human mobility data. This surveillance system identifies regions with real or suspected cases of COVID-19. We simultaneously harness global commercial air transportation data and geo-referenced mobile device data to reflect human mobility, also in real time. We have successfully validated these tools for COVID-19 forecasting during the course of this epidemic and published our results in peer-reviewed literature. We will first use the AI-based surveillance system to identify regions with confirmed and suspected COVID-19 cases. We will then model the spread of infection from these locations by harnessing human mobility data to identify and forecast new regions (at the city, regional, and national level) for virus importation. We will work closely with our partners in the World Health Organization, the Association of South East Asian Nations (ASEAN), and the International Air Transport Association (IATA) to use this data to help drive evidence-based public health policy in real time, with a focus on global projection strategies, and strategies for low and middle income countries in Southeast Asia.",2020,-99,University Health Network,506100,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +C20730,Unknown,"Mobilizing the Chinese Immigrant Community and Battling the Potential COVID-19 outbreak in the Greater Toronto Area: Gathering essential information, creating a mutual support quarantine network and assessing psychological impacts","The COVID-19 outbreak is raging in China and spreading across the globe. The situation is getting worse and may last longer than anyone can expect. Despite of only eight confirmed cases, Canada is now shrouded in fear and worry in face of uncertainty. The Greater Toronto Area (GTA) has one of the largest Chinese communities in the world and thus bears the brunt of the fear, anxiety, and panic. This, coupled with English language obstacles, has enabled rumors and misinformation to explode on social media. It has been suggested that the Toronto Chinese community is the most vulnerable, yet least prepared population for the potential COVID-19 outbreak. There is an urgent need to prepare and mobilize the GTA Chinese community to fight against the possible outbreak. In this context, the overarching goal of the proposed work is to assess the knowledge, develop effective epidemic control practice, and identify the psychological impacts of the disease. This will be achieved through coordinated efforts across communities, professionals, and local residents, to address three specific and inter-related objectives: 1) assessing GTA Chinese immigrants' knowledge, attitudes/beliefs, and protection practices toward COVID-19; 2) developing, evaluating, and optimizing a mutual-support quarantine network to contain COVID-19 from further spreading; and 3) assessing the psychological impacts and the associated predictors of the potential COVID-19 outbreak. The proposed project is culturally relevant, practical, and community-based. The research team is comprised of multidisciplinary researchers from the related fields of public health (epidemiology), psychology, sociology, and health policy. As part of the ongoing effort, the team has been closely working with the GTA Chinese community in various ways. This project will benefit not only the target population but also other communities in Canada.",2020,-99,Memorial University of Newfoundland,221265,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication | Indirect health impacts,2020 +C20731,Unknown,Point-of-care diagnostics of COVID-19 using isothermal amplification and CRISPR technology,"This research addresses the urgent need of rapid point-of-care diagnostics of COVID-19. The collaborative research is conducted by a multi-disciplinary team of virologists, chemists, infectious disease specialists, front-line practitioners, and public health researchers from the University of Alberta, Canadian Food Inspection Agency, and Wuhan Institute of Virology (China). The immediate priority focuses on developing two complementary techniques to be performed on-site and in resource-limited settings, in support of rapid diagnosis of COVID-19. The diagnostic innovation takes advantage of the most recent advances in chemistry, molecular biology, genome technology, and nanotechnology. Chemical reactions required for efficient amplification and sensitive detection of the viral RNA take place in a single tube at a moderate temperature, simplifying the operation procedures. The specific reaction products are visible to the naked eyes, thus eliminating the need for any elaborate equipment. The first test reads color changes, with red color indicating negative and blue color indicating positive. Readout for the second test is color band on paper strips, similar to those of pregnancy tests, with two red bands indicating positive whereas a single control band indicating negative. The mid-term priority focuses on validating and evaluating the new diagnostic tests for field applications in the epidemic center of COVID-19. Our team members in Wuhan who currently perform the standard diagnostic tests will lead this effort. Once validated and approved, the new diagnostic tools will be used to support screening and diagnosis of COVID-19 at the community level. The mid-term objective also includes adapting the point-of-care diagnostics at other collaborating sites, e.g., Karachi (Pakistan) and Nairobi (Kenya). A longer-term priority of this research includes refining the new diagnostic tools to enable monitoring of mutational changes of the virus as it continues to evolve.",2020,-99,University of Alberta,621034.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +C20732,Unknown,Policy Implementation and Communication Lessons from Alberta's Acute and Primary Care Environments During the COVID-19 Response,"As international, national, or provincial agencies develop policies to combat an outbreak like COVID-19, these policies will always be interpreted through the local context and culture of the healthcare workers on the front lines. Context and culture are important elements of any public health response, not just in communities, but in clinical settings as well. This project will use a mix of qualitative methods to evaluate how COVID-19 preparedness and response policies are being transmitted and implemented in acute and primary care facilities in the province of Alberta. Through site visits, task analyses, and interviews with public health professionals and clinicians at the provincial level, we will conduct a systematic assessment of how policies, protocols, priorities and communication channels are functioning. We will be asking our participants how they are implementing and prioritizing: staff, case, and space management policies; referral and isolation protocols; and surveillance and risk communication priorities in preparation for the appearance of COVID-19. As well as offering a detailed description of how things are playing out on the ground, our research will identify gaps, challenges, and opportunities for improving existing response efforts. We will be writing reports and papers that help Alberta and other provinces plan for future public health emergencies. These reports and papers will focus on how context and culture impact clinical capabilities for public health preparedness and policy implementation.",2020,-99,The University of Calgary,322234.5,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +C20733,Unknown,Préserver le lien des résidents en ESLD atteints de troubles cognitifs avec leurs proches en contexte de pandémie : évaluation de la mise en œuvre et des effets d'interventions virtuelles et en personnes [Preserving the link of LTCF residents with cognitive disorders with their loved ones in the context of a pandemic: evaluation of the implementation and effects of virtual and in-person interventions],"Google translate: In Quebec, nearly 70% of deaths linked to COVID-19 are people living in long-term care facilities (ESLD). The restrictions imposed to reduce the transmission of the virus have deleterious effects on the elderly and consequences on caregivers. In order to mitigate the negative effects, different strategies are used to maintain contact with loved ones and thus promote actions to protect the mental and physical state of seniors. However, the evaluation of the implementation and effects of innovative interventions in the context of a pandemic in elderly people with cognitive impairment have not been studied to date in Canada. In collaboration with 5 LTCH partners, the goal of the project is to evaluate the implementation process, the viability and the acceptability of interventions aimed at favoring the presence of loved ones (in person or virtually), as well as the effects on residents, their loved ones and related costs. An evaluative research estimate is preferred. A multiple case study will be used to describe the reality of the target environments and actors, grasp the complex relationships between the different factors, document the degree and variability of implementation in the different environments and their results. Residents with cognitive disorders, their caregivers and members of the care team will be recruited in each setting. Interventions that maintain contact with loved ones and are supported by the living environment can mitigate the repercussions of isolation and have a considerable impact on anxiety, cognitive and behavioral symptoms, and quality of life. By giving a voice to elders, relatives, and caregivers, documentation of acceptability will add evidence that tailored, humane interventions are viable and relevant in LTCFs.]",2020,-99,Université Laval,150000,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Caregivers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +C20734,Unknown,PROTECH - Pandemic Rapid-response Optimization To Enhance Community-resilience and Health,"Global travel and trade have led to the spread of contagious diseases around the world, or pandemics. News about emerging pandemics often bring out fear and anxiety in the public. Recent public response to the new coronavirus (COVID-19) outbreak reflected blame, fear, and racism against the Chinese communities. We have learned during the 2003 SARS crisis in Toronto that stigma could lead to crushing harm on the health, psychological, social, and economic well-being of the affected communities. In response to the potential negative impacts of COVID-19 on the Chinese communities, our team proposes a cutting-edge model - Pandemic Rapid-response Optimization To Enhance Community-Resilience and Health (PROTECH) that consists of three interrelated components: (1) an online resource hub that provides accurate and timely information on COVID-19, and practical ways to cope with fear and anxiety; (2) an online group training with live video meeting to reduce stigma/stress and promote resilience among affected groups (individuals tested positive; healthcare providers experiencing stress or burnout, community leaders); and (3) a framework that sustains the first two components and aligns people, processes, and resources together. Our team includes clinicians, researchers, and leaders from diverse public, arts, and business sectors. We will also reach out to key opinion leaders and community influencers to mobilize the Chinese and other affected communities. We will use focus groups, surveys, and note-taking on project activities to examine the effectiveness of PROTECH in reducing stress and stigma, and promoting collective resilience, or how to best support the affected groups to keep well despite the challenges. Finally, the PROTECH model can be adapted and used in different communities across Canada and other countries for future pandemic outbreaks.",2020,-99,Ryerson University,375000,Human Populations,Asian | Unspecified,Unspecified,Urban Population/Setting,Minority communities unspecified | Other,Health Personnel | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,Innovation,,,Canada,Canada,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Communication | Indirect health impacts | Health workforce,2020 +C20735,Unknown,"Socio-Cultural Implications of COVID-19: Educating, Engaging & Empowering the Public","A novel infectious disease, COVID-19, is affecting mainland China and is now in at least 27 other countries. Since December 2019, over 67,000 people have been infected and more than 1,500 have died. Infectious disease outbreaks pose a severe threat to the physical and mental health of individuals and populations worldwide. A better understanding of social and cultural factors that contribute to public knowledge and perceptions of COVID-19 are needed to develop evidence informed strategies to combat misinformation, stigma and fear. In response to this challenge this study proposes to develop a national knowledge translation (KT) campaign to enhance public knowledge, understand public perceptions and develop targeted interventions to close identified public knowledge gaps. This will be achieved in three phases: i) Focus groups with members of the public from 5 provinces to identify major factors influencing public knowledge, perceptions and behaviours during the COVID-19 outbreak. ii) National survey with 1000 members of the public across Canada to create a comprehensive list of top public knowledge gaps, perceptions, and behaviours related to the COVID-19. iii) A national knowledge translation (KT) Campaign to educate, empower and engage the public to increase knowledge and foster positive public change in the context of the COVID-19 epidemic. This study will target the Canadian public with the ultimate goal to educate, empower and engage members of the public to be informed stewards of their health knowledge in relation to the current outbreak by strengthening public understanding of the impact of COVID-19 on individuals and communities and providing evidence informed interventions to inform social and public health responses.",2020,-99,Dalhousie University,300870.75,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +C20736,Unknown,Understanding the effects of public health outbreak control policies and implementation on individuals and communities: a path to improving COVID-19 policy effectiveness,"This project will examine the cultural dimensions of the coronavirus (COVID-19) epidemic such as examining how individuals and communities understand and react to the disease, studying the response of public health, and exploring how public health policy affects individuals and communities. While public health policies are required to control an infectious disease outbreak, these policies can adversely affect individuals and communities. Quarantine, limitations in movement and public gathering, and other restrictive measures can put a social and economic burden on individuals, which may be disproportionate, depending on their socioeconomic status and other factors. Healthcare providers are both involved in administering the policy but are also put at grave risk in caring for patients. This will be a multiprovince, multicountry study in Canada (British Columbia, Ontario, Nova Scotia), Bangladesh, and China (Guangdong). We will use qualitative methodology (document review, key informant interviews, focus groups) and quantitative methods (surveys) to examine policy and implementation from the public health/policy perspective as well perspectives of the media, communities, healthcare providers, patients and their caregivers, and members of the general public. These data will be used to improve the process by which public health policies are created and implemented.",2020,-99,Dalhousie University,374928,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas | South-East Asia | Western Pacific,,,,Canada,Canada | Bangladesh | China,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +C20737,Unknown,Understanding the pathogenesis of COVID-19,"Pulmonary infections by viruses such virulent Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) and Middle East Respiratory Syndrome (MeRS) CoV associated with significant morbidity and mortality. Clinically, infections by these viruses are associated with a pronounced lung inflammation, causing respiratory problems that often develop in secondary pneumonia. Inflammation is the result of immune activation in response to infection. When activation is too pronounced or sustained for extended periods of time, complications occur. Two main mediators of inflammation are known: Cytokines and lipid mediators of inflammation (LMI). In the current proposal we will study the inflammatory response during infection/exposure of lung and blood cells to the newly described COVID-19 and compare this response to that of SARS-CoV-2 and MeRS-CoV to obtain correlates of pathogenicity between these viruses. We will use primary lung cells and white blood cells from donors to conduct our studies. The mediators of inflammation will be identified and quantitated using state of the art methodology available in our laboratories. More than 200 LMI and 150 cytokine/cytokine receptors will be examined. Upon completion of this proposal, a detailed analysis of the response of primary epithelial cells and leukocytes to COVID-19 will be obtained, enabling the rational design of therapeutic strategies to help combat COVID-19.",2020,-99,CHU de Québec,294675,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Americas,,,,Canada,Canada,Clinical characterisation and management,Disease pathogenesis,2020 +C20743,MC_PC_20062,RECOVERY/Phase 2 Therapeutic Trials Reconfiguration,"The RECOVERY trial is jointly funded by the NIHR and UK Research and Innovation (UKRI), with research delivery supported by the NIHR's Clinical Research Network at 176 hospital sites across the UK. The trial is being coordinated by researchers at the University of Oxford, which acts as the sponsor for the research. This award is jointly funded (50:50) between the UKRI and the NIHR. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. With this support, to date the trial has recruited over 12,000 participants - making it the world's largest trial of potential COVID-19 treatments. RECOVERY/Phase 2 Therapeutic Trials Reconfiguration also known as Recovery+ is additional support to continue the work of the initial RECOVERY trial titled COVID-19: multi-arm, multi stage adaptive clinical trial (CoV-MAMS) - MC_PC_19056.",2020,2023,University of Oxford,21868820.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Phase 2 clinical trial,2020 +C20745,BB/V01983X/1,An accurate eukaryotic plasma membrane assay for coronavirus binding,"This project focuses on the development of a surface based ACE2 membrane sensor that will provide a highly realistic model of coronavirus cell surface binding and be amenable to high throughput screening. SARS-CoV-2 enters mammalian cells by a transduction pathway whose first stage is the interaction of its spike (S) protein on the viral surface with ACE2 (angiotensin converting enzyme-2), a type-1 transmembrane protein. Once the virus attaches to the membrane surface the S protein is modified by a cell surface protease (TMPRSS2) to form a fusion peptide which inserts into the membrane and facilitates viral transduction. Current S protein/ACE2 interaction studies have primarily focused on utilising a recombinant soluble construct of ACE2 and thus do not truly represent the in vivo processes occurring. Using our expertise with surface based supported bilayers we will fabricate an accurate membrane mimetic of the eukaryotic membrane containing full length ACE2 on a sensor surface. Neutron Reflectometry together with quartz crystal microbalance (QCM) will be used to validate the surface assemblage and viral component binding. The system will then be further developed to include other components known to be involved in ACE2/Coronavirus interaction (e.g. TMPRSS2 & B0AT1), to provide a realistic model of coronavirus membrane surface interaction. This system will be directly translatable to techniques amenable to high throughput screening (QCM and surface plasmon resonance). This will aid the scientific community in studying coronavirus membrane binding and can be used as a diagnostic tool for the identification of inhibitors of coronavirus-membrane interactions.",2020,2021,University of Birmingham,140407.39,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Disease models,2020 +C20746,ES/W002507/1,COHERE phase 2: Living systematic reviews and evidence and gap map on determinants of COVID-19 Health Related Behaviour,"Health-protective behaviours, like washing your hands, wearing a facemask and social distancing, can help to protect people from contracting or transmitting COVID and other similar serious respiratory infections. This project aims to help us understand more about the factors that influence these behaviours in the general public. This project represents the second phase of our research. In phase one we conducted a rapid review of published studies that looked at the things that influenced uptake of these protective behaviours during COVID or during previous outbreaks of similar serious respiratory infections, for example SARS, MERS and H1N1 (swine flu). We quickly put the results of these studies together to understand what influences people's health protective behaviours. By putting the data from different studies together in a new analysis, a meta-analysis, we were also able to find out how strong these relationships are. Finally we assessed the quality of the studies we found so that we know how confident we can be that the evidence we have is good enough to support our conclusions. We completed the first phase quickly to provide answers to urgent questions about COVID. Working quickly meant that we only had time to look for published, peer-reviewed studies and not all the studies conducted that hadn't yet been published in scientific journals. As well as that, there has been a very large increase in the number of potentially relevant studies conducted in the context of COVID-19 over the last nine months, since we last searched for studies. In phase two, we are going to repeat this process of finding and putting evidence together but this time we have more time and resources to search more thoroughly. To begin with, we will publish an open access 'evidence and gap map' that will contain information on all of the studies we have already found (in phase 1). This will be open to anyone to use and allow other researchers, policy makers and those who fund research to see what evidence we already know about and where the gaps in our knowledge are. The next step will be to do a thorough search for any new studies and any unpublished work that we didn't find in phase 1. We will then check every study we find to see if it can tell us something about why people do, or do not, adopt the behaviours that help protect against getting or passing on COVID-19. When we find new relevant studies we will add them to our map. Once we have gathered up all of the relevant studies we will extract information about each study, such as who took part, how the behaviours of interest were measured, what factors related to relevant behaviours and any information on how strongly related each factor is to each behaviour. We will also assess the quality of each study we include. Finally, we will put all of the relevant information from the studies we find together in a new analysis and then publish a separate systematic review of the evidence on each behaviour of interest (washing hands, wearing masks, social distancing, physical distancing, self-isolation or quarantine, disinfecting surfaces). We will follow all of the established guidelines and best practices for conducting research of this kind, such as Cochrane and Campbell guidance. The last part of our project will be to update our searches to capture any new evidence as it emerges and integrate that into the reviews. This is called a 'living review' and the reviews will remain living for at least the life of the project (18 months). We will work on using technology to find ways to make this process as efficient as possible so that our reviews stays up to date and available to use. The main aim of our project is to understand what determines people's positive health protective behaviours. This in turn will help others to develop better ways to support people to protect themselves and others from co",2021,2022,Queen's University of Belfast,354365.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +C20747,MC_PC_20004,COVID-19 GenOMICC-GENOMICS ENGLAND PARTNERSHIP,"GenOMICC (Genetics Of Mortality In Critical Care) is a global collaborative study to understand the genetic basis of critical illness. For the GenOMICC-Covid-19 programme there are several key inter-related studies currently being undertaken: Genomics England/GenOMICC (GeL/GenOMICC), led by Kenneth Baillie, Edinburgh 1. Overall investment is provided by DH, NIHR Bioresource (in kind), UKRI (MRC) and LifeArc. Objectives: Using whole genome sequencing (WGS), to investigate genetic links to patients severely affected by Covid-19 in: a. 20,000 severely affected individuals: (requiring admission to intensive care) compared with 15,000 mildly affected unaffected individuals. b. Up to 1000 trios (mother/father/affected individual): severely affected younger (under 40) individual with no other underlying health conditions to look for rare variants. 2. UKRI's funding contribution (up to £1.5m) is targeted towards 1b, in partnership with NIHR BioResource (recruiting and phenotyping, in kind contribution of £1m). Additionally, UKRI's funding is supporting progress towards the GeL target of WGS of 4000 under 50-year olds. 3. Short-term deliverables are identification of genetic variants associated with severe symptoms (e.g. recent publication Genetic mechanisms of critical illness in Covid-19). Risks include delays due to recruitment (e.g. depending on timing of a 'second wave'), and delivery, to be addressed through mile-stoning of outputs by the funders.",2020,2021,University of Edinburgh,1706651.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2020 +C20748,MC_PC_21004,Emergency C-19 Response,"The MRC is pleased to confirm additional capital funding for the MRC/UVRI and LSHTM Research Unit Uganda up to the value of £27,000 to support the Centres important work on COVID-19. This exceptional award is being made in recognition of the fact that research will be critical in overcoming this epidemic.",2021,2021,MRC/UVRI and LSHTM Uganda Research Unit,30719.74,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa,Africa,,,,Uganda,Uganda,,,2021 +C20749,MC_PC_21051,SARS-CoV 2 imaging study award to the UK Biobank,"The Medical Research Council (MRC) has agreed to provide a COVID-19 Support Fund award to UK Biobank to help underpin short-term stability and to avoid deterioration of strategic, national scientific capability as a result of impacts of the COVID-19 pandemic. Purpose By accepting this award, the organisation agrees to use the MRC COVID-19 Support Fund to help ensure MRC objectives continue to be met, the value of MRC investments continue to be realised, and to sustain the research skills and capability within their organisation that will be needed to underpin the post-pandemic national recovery. The award is specifically to maximise the number of participants within the core imaging programme.",2021,2022,UK Biobank,4763304.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,,,2021 +C20750,MR/W021420/1,Using data to improve public health: COVID-19 secondment,"The development and wide-scale deployment of COVID-19 vaccines has increasingly decoupled SARS-CoV-2 infection from its most severe sequelae. Each licensed vaccine has followed a pipeline of preclinical and clinical development that is tailored towards establishing its safety and efficacy. However, considerable uncertainty remains regarding the real-world effectiveness of COVID-19 vaccines, and the extent to which this is impacted by comorbidity status, dosing interval, and variants of concern (including those that have emerged since the completion of Phase III efficacy studies). The analysis of electronic health records has the potential to address key questions regarding real-world COVID-19 vaccine effectiveness with unprecedented speed, scale, and precision. In particular, OpenSAFELY is an open-source platform that links the electronic health records of over 58 million individuals in the UK, providing up-to-date information on demography, vaccination status, and SARS-CoV-2 infection and outcome, while preserving patient confidentiality. My secondment will harness the OpenSAFELY platform to address key evidence gaps relating to real-world COVID-19 vaccine effectiveness. First, I will evaluate primary series and booster dose coverage in key risk groups, including individuals affected by chronic kidney disease. Second, focusing on these high-risk groups, I will use retrospective cohorts nested within OpenSAFELY to compare the effectiveness of different primary vaccine schedules (e.g. BNT162b2 vs ChAdOx1-S) and booster regimens (e.g. homologous vs heterologous boosters). Finally, I will explore the impact of several key factors on the strength and durability of vaccine protection, with a particular emphasis on dose interval and natural SARS-CoV-2 infection (including confirmed positive tests occurring before or after vaccination). In doing so, my secondment will harness electronic health records to address important evidence gaps regarding the ongoing COVID-19 vaccine roll-out.",2022,2022,London School of Hygiene & Tropical Medicine,82239.01,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +C20751,MR/W021447/1,Using data to improve public health: COVID-19 secondment,"Events following SARS-CoV-2 infection in the era of delta - Technical Summary Aim: The aim of this project is to understand the risk of adverse health events following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the era of delta among the fully vaccinated and the electively unvaccinated. Research Questions: 1. Among vaccinated individuals in the era of the delta variant of SARS-CoV-2, are there higher rates of an incident outcome in those with and without SARS-CoV-2 infection, before and after adjustment for potential confounders? 2. Among electively unvaccinated individuals (individuals eligible for vaccination that have chosen not to receive it) in the era of the delta variant of SARS-CoV-2, are there higher rates of an incident outcome in those with and without SARS-CoV-2 infection, before and after adjustment for potential confounders? Methods: This research will be conducted using the OpenSafely electronic health records data source, with a start date of 01-06-2021 (when delta was thought to be ubiquitous) and end date corresponding to date of most recent data collection. Individual follow-up will end at the earliest date of outcome event, death, or study end date. Exposure to SARS-COV-2 infection will be defined as the first date of a confirmed COVID event after index date. Each outcome will be defined as the first event occurring within the follow-up period, the events of interest are; Acute myocardial infarction, Ischaemic stroke, Pulmonary embolism, Deep vein thrombosis, Transient ischaemic attack, Subarachnoid haemorrhage and haemorrhagic stroke, Heart failure, Angina, Arterial thrombosis events, and Venous thromboembolism events. Cox regression models with a calendar time scale will be fitted to ensure analyses account for changes with calendar time in rates of the outcome event. Hazard ratios will be estimated for events of different types before and after exposure, and by time since exposure. Results will be adjusted for potential confounders including Sex, Age, Ethnicity, Deprivation, Region, Consultation rate, Number of regular medications, Smoking status, Obesity, previous events, Combined oral contraceptive pill, and Hormone replacement therapy.",2022,2022,University of Leicester,72704.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2022 +C20752,MR/W021641/1,Repurposing approved drugs as potent antiviral combinations to treat COVID-19 disease,"We hypothesise that antiviral drug combinations against SARS-CoV-2, suitable for oral or intranasal administration, will provide therapeutic opportunities for ambulatory COVID-19 patients that are more efficacious and with less propensity for the development of drug-resistant mutants. We will address this hypothesis by exploiting a comprehensive robust multi-step pre-clinical in vitro and in vivo testing platform for novel drug combinations that ranges from HTS screening of unbiased combinations of drugs with known antiviral activities against SARS-CoV-2 and pharmacometrics to ensure potential for human use, to therapeutic efficacy models in SARS-CoV-2-infected well-differentiated primary human airway epithelial cell cultures (WD-PAECs) and animals (Syrian golden hamsters and hACE2 mice) with the most promising combination drug hits. Promising hits will be subjected to antiviral screening against a panel of variants of concern (VOCs) and endogenously circulating coronaviruses to ensure broad activity against SARS-CoV-2 VOCs and the potential for pan-CoV antiviral activities.We will extend this testing platform to non-biased screening of extensive approved drug libraries that have not previously been mined for drug combinations to treat COVID-19 with a view to ensuring a pipeline of future therapies against SARS-CoV-2.It should also be noted that we will make our pipeline available to the UK-CTAP to make recommendations for candidate evaluation. For this, a candidate/combination could enter evaluation at any WP that is appropriate given data that are available at the time.This project will provide comprehensive data to enable robust decision making regarding the entry of combination antiviral drugs hits into the UK COVID-19 clinical trial platforms or the de-prioritisation of drugs from further development.",2022,2024,Queen's University Belfast,1823652.04,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +C20753,MR/W025140/1,A longitudinal study of SARS-CoV-2 evolution and molecular characterisation of variants in immunocompromised individuals with persistent infection,"Immunocompromised individuals can develop persistent infection with SARS-CoV-2. Mutations accrue due to ongoing replication, creating new 'variants' of the virus. These mutations have the potential to alter host-pathogen interaction, potentially affecting pathogenesis, transmissibility, severity of disease and susceptibility to vaccines or treatment. This longitudinal study will characterise viral evolution and the variants that arise during persistent infection with SARS-CoV-2, followed by molecular characterisation of these variants in vitro. By studying longitudinal viral isolates and sera from the same individual, sequential mutations can be studied to judge their effect on host-pathogen interaction. The aims of this proposal include to 1) describe the patterns of SARS-CoV-2 intrahost evolution longitudinally during persistent infection, 2) correlate the emergence of SARS-CoV-2 variants with clinical course, immunosuppression and antiviral treatment, 3) characterise emergent variants in vitro, including experiments to judge neutralisation by antibodies and resistance to interferon. Genomic sequencing of viral isolates using a deep sequencing protocol on Illumina technology will allow determination of the consensus genome and intrahost single nucleotide variants (iSNVs). The presence and frequency of iSNVs over time will be monitored, and in response to treatments for SARS-CoV-2 and other immunomodulating therapies for pre-existing conditions. Viral isolates will be cultured for in vitro molecular characterisation experiments. Successive genomic mutations will be judged for their effect on neutralisation by antibodies and changes in susceptibility of the virus to interferon. Longitudinal serum samples from persistently infected individuals will be used in autologous neutralisation studies on the cultured virus. Initial research utilises existing ethical approval to analyse already stored, residual samples from GSTT in collaboration with KCL and UCL.",2022,2025,King's College London,318499.94,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2022 +C20754,MR/W029200/1,Mass evaluation of lateral flow immunoassays for the detection of SARS-CoV-2 antibody responses in immunosuppressed people (MELODY Study),"The MELODY Study aims to assess:1The proportion of immunosuppressed patients who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses), and the demographic, disease, and treatment characteristics that influence antibody status. 2If the detection of antibodies inversely correlates with subsequent risk of SARS-CoV2 infection and/or severity of disease.Building on the successful methodology used in the REACT2 Study (community assessment of SARS-CoV-2 antibody tests), the study will assess self-administered LFIAs in 36,000 patients, who have completed their primary COVID-19 vaccination course. The study will recruit; a) solid organ transplant recipients, b) patients with autoimmune diseases receiving immunosuppression, c) patients with haematological malignancies. The study will utilise the digital web platform and research expertise of Ipsos MORI linked with the patient registries, UK Transplant Registry and National Disease Registration Service (NDRS) at Public Health England, which comprises the National Cancer Registration and Analysis Service (NCRAS) and the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). Patients will be recruited following a letter of invitation or via an 'opt-in' option on the study web portal. Once consent is registered via the portal, a LFIA kit will be sent to the participant together with instructions to use. Participants will be required to fill in a brief questionnaire and to upload the results of their tests, together with a photograph of the test using a mobile phone, if possible. Once all the data is returned, Ipsos MORI will collate and send the data back to the registries for analysis. The registries will subsequently capture all RT-qPCR proven infection episodes and outcomes over the course of the 6 month study period, and compare outcomes by antibody status.",2021,2022,Imperial College London,927289.99,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Diagnostics | Immunity | Characterisation of vaccine-induced immunity,2021 +C20942,10023490,A.I. forecasting to reduce food waste - COVID-19 impact,"The UK hospitality industry generates over 1 million tonnes of food waste each year, equivalent to approximately £3 billion in cost and over 4.5 million tonnes of CO2\. At the same time, UK restaurants yield a meager 3-5% average profit margin, making it one of the least profitable industries in the country. This economic struggle has been dramatically exacerbated by the COVID crisis. Through effective food waste reduction, restaurants can boost profitability by up to 2pp, while drastically reducing the environmental impact of their operations. The key to reducing food waste lies in accurate demand forecasting. Restaurants order their perishable inventory days and weeks before selling dishes to their customers. Given that most restaurants rely on rigid 4-week demand averages and gut instinct to make their procurement decisions, food orders are routinely in excess of real demand - creating food waste. Tenzo will research & develop a cutting-edge forecasting tool, which will allow restaurant businesses to accurately forecast customer demand. Utilising powerful artificial intelligence algorithms, the tool will achieve the following objectives: * Generate accurate restaurant sales forecasts based on historical sales, weather, public events and other features * Split daily forecasts into item-level and hourly projections * Provide those forecasts to frontline workers (chefs, section managers, etc.) within a user-friendly mobile app - enabling them to know easily how much food to: * prepare and when (e.g. how much chicken to grill every hour); and * order and when (e.g. how much fish to order for next week). Tenzo's project will focus on finding the most accurate forecasting algorithms and combining them with a user-friendly software interface to ensure frontline workers are empowered to reduce food waste in their day-to-day operations. By 2024, our tool could reduce annual UK hospitality food waste by over 38,000 tonnes, CO2 by over 175,000 tonnes and restaurant costs by over £20 million.",2021,2022,TENZO LIMITED,44700.63,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +C20955,10008614,T Cell Responder,"* Protective immunity to SARS-CoV-2, like other viruses, depends on a combined immune response by specific antibodies and T lymphocytes. As we race to immunise the world and end the pandemic, there is considerable unmet need for better, high-throughput immune monitoring. In diverse settings, from healthcare and public health planning to travel and hospitality, there is demand to know if people are carrying immunity. These answers also impact if and when people will require vaccine boosters. While the increased momentum behind antibody testing has supplied finely-tuned, cost-effective, reliable tests, T lymphocyte assays remain cumbersome, costly and limited to specialist labs. The team at Imperial College are leaders in T lymphocyte immunology and have, since the start of the pandemic, been at the forefront of characterising immunity to the virus. However, the assays involve complex cell separations and equipment. We have invested considerable effort in defining which aspects of immunity are truly specific to SARS-CoV-2 and not the result of cross-reactivity with the related common cold viruses. Recent work has been devoted to reimagining T lymphocyte assays to consider what it would take to demonstrate, rapidly, that a small blood sample contains specific cells responding to the virus - that is, who can be defined as having immune memory for this virus - 'a T cell responder'. We have been able to show novel biomarkers of the response, measurable in immune people in a matter of hours. During this project we plan to refine our observations to the extent of producing a pilot point-of-care test that can be developed as a test of T lymphocyte immunity. We envisage utilisation in many settings: international immunity certificates, management of optimal vaccine schedules in at-risk patient groups, public health decisions on when to boost vaccines. Once optimised, the approach can easily be extended to other settings, from immunity to other pathogens, to monitoring of the anti-tumour response in cancer patients given immunotherapy. For these reasons, we have given the project and proposed kit an easy and self-explanatory name - 'T Cell Responder'.",2021,2022,Imperial College London,536524.72,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Europe,Innovation,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2021 +C21059,,"Boosting Public Discourse: Towards a Targeted, Evidence-Based Strategy to Improve Moral Reasoning","The public discourses on Covid-19 during the pandemic years have highlighted the importance of a common understanding of key moral terms such as 'autonomy', 'solidarity, or 'proportionality' for a successful communication between autorities, the media, or the health system, and the general public. With this project we aim at contributing to a better understanding of how public discourse may succeed due to an unreflective use of moral key terms, and develop a strategy for improving readiness and competency to participate in public discourse. Specifically, we will analyze and map how moral key terms are used and comprehended in press releases from the government, media outlets, social media, for example. We will then identify common conceptual and argumentative pitfalls regarding the use of moral key terms in public discourses, and, based on this analysis, develop and pilot-test a simple game for adolescents that empowers users to reflect on their understanding of moral key terms and to train their clear and consistent use in moral arguments. Empowering citizens, particularly the young generation, to engage constructively in high-quality public discourses will facilitate the search for the best actions to take in times of crisis, increase the democratic legitimation of measures and strengthen societal resilience and cohesion.",2023,2025,Swiss Tropical and Public Health Institute,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2023 +C21060,,"Mathematical modelling to examine disease, control measures, vaccine interactions and resistance to guide public health and disease elimination strategies","Mathematical models are increasingly important to understand new and existing diseases and for planning how we tackle these diseases. Models with enough detail of how a disease interacts with the body, how drugs and other interventions affect the disease, and how health systems respond can help us evaluate the best approaches for addressing diseases. In this project, we will examine the impact of pathogen resistance to disease interventions. We address two important pathogens: malaria and SARS-Cov-2. As we get closer to eliminating malaria and other diseases, preventing diseases from evolving resistance to response measures becomes ever more critical. Since the characteristics of resistance differ depending on the level of disease, public health strategies are likely to change as we near elimination. In the current global SARS-CoV-2 pandemic, we are at a crucial moment to define strategies for deploying vaccines. Since the virus that causes COVID-19 is likely to mutate further, new vaccine-resistant variants may emerge. We will examine how resistance to vaccines and other treatment measures comes about, and will define intervention roll-out strategies to best avoid resistance for different pathogens. Our work will bring together mathematical models and what we know about how diseases evolve, to come up with the best possible health policies and vaccine roll-out plans over the coming years. We will build and calibrate detailed parasite models, mosquito-to-human transmission models and adapt individual-level models for malaria. We will also adapt models of SARS-CoV-2 to examine the emergence of vaccine-resistant COVID variants. These new models will help identify key disease characteristics that drive the evolution of resistance and the spread of resistant pathogens. We will examine resistance to vaccines, drugs and immune response therapies; in the case of malaria, we will also examine the spread of mosquitoes resistant to insecticides. Our work will provide evidence to support the selection of disease control and elimination strategies and inform decision-making, especially surrounding resistance. Of immediate relevance to malaria and COVID-19, it will also inform efforts to control other diseases.",2021,2023,Swiss Tropical and Public Health Institute,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2021 +C21061,,PubliCo - PubliCo - an experimental online platform for COVID-19 related public perception,"Effective public health measures to contain the Covid-19 pandemic require cooperation between governments and society. For this to happen, political decision-makers must be aware of how the population perceives the Corona crisis, and the political decisions taken must be comprehensible to the public in order to be acceptable. The aim of the project is to set up and operate the interactive online platform ""PubliCo"", which is being developed together with scientists from various disciplines, communication and design experts, and citizens. With a set of questions tailored to the situation the public perception is assessed: How are the risk of infection and the accompanying measures perceived? How are measures like contact tracing and physical distancing accepted over a longer time period? What moral conflicts exist when it comes to who should first have access to a newly developed vaccine? What are the implication of the Covid-19 crisis on people's everyday life, e.g. in their work environment or in interpersonal relationships? The project is led by the Institute of Biomedical Ethics and History of Medicine (IBME) at the University of Zurich in collaboration with the Society, Gender and Health Unit at Swiss TPH. Swiss TPH is responsible for the citizen science component where different people report on their Covid-19-related experiences and reflections. This data is continuously analyzed, contributing to the setting of priorities for research and action.",2020,2022,Swiss Tropical and Public Health Institute,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Europe,Digital Health,,,Switzerland,Switzerland,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in the Allocation of Resources | Approaches to public health interventions | Communication,2020 +C21064,,Provision of Technical Assistance for Covid-19 Vaccine Delivery Preparation and Readiness,"The introduction of a new vaccine provides many opportunities as well as challenges to improve a country's overall immunization programme as well as its health services and health system. Many of the activities carried out to prepare, implement and monitor the introduction of COVID-19 vaccination will provide opportunities to improve the immunization programme and to identify best practices that could be applied to other health programmes and services. Activities that should be integrated into the national primary health care (PHC) operational framework include: microplanning, using an evidence-based decision-making process to govern the introduction of the COVID-19 vaccine; strengthening human resource management; training for new vaccine introduction; establishing new contact points for vaccination across the life course; ensuring traceability systems and technologies are leveraged to ensure the integrity and efficiency of supply chains, improving and expanding integrated project management and the supply chain; enhancing integrated disease surveillance and adverse events following immunization (AEFI) monitoring and reporting systems; and conducting integrated advocacy and communications activities to promote demand for vaccination as part of increasing overall demand and acceptability of all essential PHC services. Moreover, the most vulnerable include older populations, therefore building capacity for adult immunizations, including synergy of COVID-19 vaccine with influenza vaccination, will be important. Gavi and Swiss TPH came into a framework agreement for an initial period of 13 months until 31st December 2021, with the possibility to extend for an additional 12 months until 31st December 2022 to bring support to the Expanded Programme of Immunisation (EPI) of 11 countries. The Gambia is one of these countries for which SCIH/SPMU has signed a technical assistance mandate to deliver some of the above mentioned activities in the framework of COVID-19 vaccine introduction.",2021,2021,Swiss Tropical and Public Health Institute,,Human Populations | Other,Unspecified,Older adults (65 and older) | Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Global Alliance for Vaccines and Immunization (GAVI),Switzerland,Europe,Europe,Europe,,,,Switzerland,Switzerland,"Vaccines research, development and implementation | Health Systems Research","Vaccine logistics and supply chains and distribution strategies | Medicines, vaccines & other technologies",2021 +C21066,,EXPAND Chad - Expanding NTD and COVID-19 control to mobile pastoralists in Chad,"The EXPAND project aims to expanding neglected tropical diseases (NTDs) and COVID-19 surveillance and control to mobile pastoralists in Chad through the establishment of integrated surveillance and access to health information and services. It also works towards the prevention and treatment of COVID-19 and NTDs in the mobile pastoralist populations. Funding is provided by the ASCEND Learning and Innovation Fund, sponsored by FCDO (previously DfID). The project will raise awareness about hygiene behaviour and infectious diseases symptoms, facilitate disease surveillance through simple reporting mechanisms and establish permanent access to the mobile pastoralist population by training community volunteers who serve as points of contact. While the whole community will profit from the intervention through health education, surveillance and healthier animals, the project also ensures that access to diagnostic and health services is particularly available for children and women, the most vulnerable groups within these communities.",2020,2022,Swiss TPH,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,Africa,Africa,,,,Chad,Chad,"Epidemiological studies | Policies for public health, disease control & community resilience | Health Systems Research",Disease surveillance & mapping | Community engagement | Health information systems,2020 +C21075,1R01HD107522-01,Promoting Prosocial Behavior in Syndromic Intellectual and Developmental Disabilities,"Project Summary/Abstract: The enormous impact of COVID-19 service disruptions on individuals with intellectual and developmental disabilities (IDDs) has highlighted the critically urgent need to increase access to mental and behavioral health services. Within IDD populations, genetic syndromes associated with IDDs (""syndromic IDDs"") represent a particularly vulnerable subgroup. Many patients with syndromic IDDs present with medically complex phenotypes and remain minimally verbal even into adulthood, creating challenges accessing and benefiting from community-based interventions. Several reports point to extreme behavior and communication challenges as the most pressing behavioral health concerns for this population. Our near-term goals seek to identify effective approaches to target the more severe cognitive and behavioral phenotypes found in syndromic IDDs. Here, we propose adaptations to function-based treatment (FBT) - an already well-established, person- centered applied behavior analysis (ABA) model focused on replacing challenging behaviors with prosocial communication and behavior responses. Using the Planned Adaptation approach, proactive adaptations to improve the fit of FBT with the syndromic IDD population include syndrome-specific characterizations to inform phenotype-environment interactions, systematic screening for automatically reinforced behaviors which are often excluded from published FBT approaches, and adjustments to support minimally verbal individuals. This proposal draws upon the expertise of the investigative group in syndromic IDDs, conventional and telehealth behavioral interventions, and implementation sciences to evaluate the adapted, parent-implemented, telehealth FBT model for syndromic IDDs (FBTsIDD). The goal of this fully remote hybrid type 1 effectiveness- implementation study is to test FBTsIDD as delivered by non-specialist providers housed in medical hubs serving individuals with syndromic IDDs. Aim 1 involves a 24-week randomized control trial (RCT) that will randomize 80 children (ages 2 to 12 years) with syndromic IDDs and moderate to severe intellectual disability (ID) and their caregivers and randomize them into FBTsIDD or positive-parenting treatment (Treatment as Usual, TAU). Our overarching hypothesis is that FBTsIDD will be associated with significant reductions in challenging behaviors compared to TAU on independent evaluator ratings using a consumer-driven, Parent Target Problems (PTP) inventory and standardized measures of behavior and functional communication. Aim 2 seeks to systematically measure and understand both planned and unplanned adaptions to FBTsIDD using the Framework for Reporting Adaptations and Modifications-Expanded (FRAME). Together, these aims provide an innovative model to develop effective, acceptable, and scalable interventions for behavioral and communication challenges across the diverse, vulnerable population of individuals with syndromic IDDs.",2022,2025,RUSH UNIVERSITY MEDICAL CENTER,813396,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C21076,1R01AI160706-01A1,Combined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacy,"PROJECT SUMMARY/ABSTRACT The high morbidity and mortality associated with Covid-19 continues to underscore the importance of effective vaccines against SARS-CoV-2. While a few promising candidates have received EUAs, the emergence of more transmissible variants which have impacted vaccine efficacy highlight the fact that several challenges remain. A successful vaccine must: 1. induce robust long-lasting protection when natural infection with coronaviruses generally leads to relatively short-lived immunity, 2. impart broad immunity as viral mutations accumulate, 3. provide potent immunity in the elderly, and 4. be safe in light of enhanced disease observed with past coronavirus vaccines. To address these challenges, this proposal aims to develop a safe, effective, and rapidly translatable adjuvant system for SARS-CoV-2 vaccines using a rationally designed combination adjuvant to target an array of key innate receptor pathways involved in antiviral immunity. Adjuvants are powerful tools for promoting fast, durable and qualitative responses most effective for a particular pathogen, especially in immune-challenged individuals. Natural viral infection stimulates strong immune responses through activation of Toll-, RIG-I-, and NOD-like receptors (TLRs, RLRs, NLRs). As induction of appropriate innate responses is crucial for long-lasting adaptive immunity and for shaping the correct types of immune responses, we will test the hypothesis that using a combination of agonists that integrate these pathways will lead to improved humoral and cellular responses towards SARS-CoV-2. To achieve this, we will combine a nanoemulsion-based adjuvant (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). We have demonstrated that simultaneous activation of TLRs, RIG-I, and NLRP3 with NE/IVT DI induces a synergistic immune response with magnified TH1-biased cellular immunity. Guided by strong preliminary data demonstrating the effectiveness of this combined adjuvant approach for improving influenza virus vaccination, and our initial studies with SARS-CoV-2 antigens, we will develop this adjuvant for use in a SARS-CoV-2 vaccine in two specific aims. In Aim 1, we will profile the immune responses elicited by NE/IVT DI with multiple SARS-CoV-2 antigens through parenteral and mucosal routes to optimize formulations and vaccination routes. In Aim 2, we will determine the protective efficacy and safety of the optimized lead vaccine platforms in challenge models of SARS-CoV-2 and define key correlates of protection. Increasing data suggests that SARS-CoV-2 elicits a weak innate response, with poor activation of critical antiviral pathways, which likely contributes to the large variability in magnitude and durability of immune responses in recovered patients. With this targeted approach, we expect to drive more robust and durable immunity while avoiding immune responses promoting vaccine related pathology. The NE adjuvant and several RIG-I agonists have demonstrated good safety profiles in phase I human trials. Thus, we expect that successful completion of this work will lead to a rapidly translatable and deliverable adjuvant compatible with multiple SARS-CoV-2 vaccine candidates, and provide much needed insight on the key effectors of protective SARS-CoV-2 immunity.",2022,2026,UNIVERSITY OF MICHIGAN AT ANN ARBOR,744600,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Clinical trial (unspecified trial phase) | Vaccine design and administration,2022 +C21077,1R21AI166944-01,Mechanisms of SARS-CoV2 translation initiation and shut-off of cellular protein synthesis,"Viruses depend on the host cell's translation apparatus and consequently, the outcome of infection is determined by the balance between a host's ability to repress viral translation via innate immune responses, and viruses' abilities to counteract them and usurp the translation apparatus. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a beta coronavirus of the family Coronaviridae that also includes the clinically important SARS-CoV and MERS- CoV. During infection, coronaviruses (CoVs) utilize a dual strategy of suppressing translation and inducing degradation of cellular mRNAs while selectively enabling viral mRNAs to gain access to the cellular translation apparatus. This strategy is mediated by the viral non-structural protein Nsp1 that binds to 40S ribosomal subunits and induces a shutdown of host protein synthesis by two mechanisms: by direct stalling of translation of cellular mRNAs, and by inducing their endonucleolytic cleavage and subsequent degradation. 5'- untranslated regions of CoV genomic and all subgenomic mRNAs contain a common ~60-70 nucleotide-long element that includes the stem-loop SL1 that confers resistance of viral mRNAs to Nsp1-mediated translational suppression and endonucleolytic cleavage. These processes are critical for viral replication and pathogenesis and although they have emerged as potential targets for chemotherapeutic inhibitors that could have broad anti-coronaviral application, they remain poorly understood: the factor requirements and molecular details of initiation on genomic and subgenomic CoV mRNAs have never been determined, the mechanism of viral evasion of Nsp1-mediated translational shut-off is obscure, and the endonuclease that is responsible for Nsp1- induced cleavage of cellular mRNAs as well as the mechanism of its recruitment to ribosomal complexes are unknown. We propose to elucidate the mechanisms of these processes by recapitulating them in vitro using individual purified translational components and dissecting their individual stages using an array of biochemical techniques. In Aim 1, we will obtain a comprehensive overview of initiation on genomic and subgenomic SARV-CoV2 mRNAs by determining the complete set of required factors, characterizing the mechanisms by which they act in this process, and by identifying properties of these mRNAs that are responsible for unique aspects of the CoV initiation process. In Aim 2, we propose to characterize the influence of Nsp1 on all stages of initiation on cellular mRNAs and to investigate the mechanism of viral evasion of Nsp1-mediated translational shut-off. Aim 3 will focus on identification of the cellular endonuclease that mediates Nsp1- induced cleavage of host cell's mRNAs, characterization of the mechanism of its action, and identification of elements in viral mRNAs that confer resistance to endonucleolytic cleavage.",2022,2024,SUNY DOWNSTATE MEDICAL CENTER,202344,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +C21078,1R21AI166575-01,Animal models of SARS-CoV-2 bacterial Coinfection,"The COVID-19 pandemic has infected over 26 million and killed at least 450,000 Americans as of 4 February 2021. Early reports show coinfections are possibly the greatest predictor of disease severity. Mixed viral/bacterial pneumonias are notoriously difficult to treat. The most extensively researched respiratory coinfection is influenza and Streptococcus pneumoniae, which contribute significant morbidity and mortality during normal respiratory infection seasons. Despite nearly two decades of vaccination with the highly effective pneumococcal conjugate vaccine (PCV), S. pneumoniae (Spn or the pneumococcus) remains a significant cause of community acquired pneumonia, sepsis, and meningitis. Much pneumococcal morbidity and mortality occurs during seasonal and pandemic flus. The physiological reasons for this are incompletely understood despite extensive investigation into this critical aspect of pneumococcal pathogenesis. Anti-viral immunological shifts, ""activation"" signals, proinflammatory upregulation of adhesins, and sialic acid availability have all been implicated. The general host responses observed during flu (fever, strong inflammatory cytokine profile, and release of DAMPS) are recapitulated during COVID-19. Spn is a normal colonizer of the human nasopharynx and a febrile state has been shown to lead to invasive pneumococcal disease by ""activating"" pneumococci. This also occurs with respiratory viruses other than flu and is likely to occur during COVID-19-associated fever, promoting the development of secondary bacterial pneumonia. A recent single-site study found S. pneumoniae to be the most common coinfection in SARS-CoV-2 infected individuals and a significant source of mortality in the aged. Although much work has been conducted with influenza/Spn coinfections, essentially nothing is known about SARS-CoV-2/Spn coinfections. As the world braces for multiple waves of SARS-CoV-2, it is of paramount importance to understand how these pathogens interact to promote severe disease. The long-term goal of this research program is to understand the interaction between SARS-CoV-2 and the pneumococcus; the objective here is to investigate the mechanisms of SARS-CoV-2 + pneumococcal disease pathogenesis during mixed infections and to model disease in appropriate animal models. The overarching hypothesis is that the host response to SARS-CoV-2 promotes invasive pneumococcal disease (IPD), ultimately resulting in increased disease severity including mixed pneumonia. More specifically, we hypothesize the inflammatory milieu created by SARS-CoV-2 infection upregulates pIGr, PafR, LamininR, and K-10, adhesins utilized by Spn to facilitate IPD. We further hypothesize that common COVID-19 treatments could impact the severity of coinfection.",2022,2024,UNIVERSITY OF TEXAS HLTH SCIENCE CENTER,232500,Bacteria | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2022 +C21079,1R21AI166870-01,Loss of A-to-I editing stimulates SARS-CoV-2 anti-viral responses,"Host pattern recognition receptors TLR3, and the DExD/H-box helicases, RIG-I and MDA5 sense viral RNA and activate IRF and NF-kB transcription factors culminating in generation of host anti-viral responses. Infection of dendritic cells (DC) or mf with SARS-CoV-2 results in an abortive infection without viral replication. In contrast, infection of normal human bronchial epithelial cells (NHBE) with SARS-CoV-2 results in robust viral replication. Infection of both cell lineages with SARS-CoV-2 generates similar robust host anti-viral responses as measured by induction of type 1 interferons (IFN1), interferon-stimulated genes (ISGs), TNF-a, IL-1, IL-6, IL-8, other cytokines, chemokines and other pro-inflammatory mediators. Alu elements make up ~10% of the human genome. Alu RNAs are abundant in human cells and, because of their repetitive nature, can form double-stranded RNAs (dsRNA) and stimulate above-cited pattern recognition receptors and a strong anti-viral response in the absence of viral infection. To prevent this, Alu RNAs are rapidly A-to-I edited by adenosine deaminase specific for dsRNA, ADAR. Our preliminary studies show that severe COVID-19 disease (COV-S) is associated with marked loss of A-to-I editing of endogenous Alu RNAs in both blood and lung, while mild COVID-19 disease (COV-M) is associated with a partial loss of A-to-I editing. Infection of DC as well as NHBE causes a marked loss of A-to-I editing of endogenous Alu RNAs. Our preliminary studies show that unedited Alu RNAs activate host dsRNA sensors and stimulate transcriptional response leading to induction of ISGs, IL-6, and IL-8. In contrast, the same Alu RNAs, if edited, as is seen in healthy controls or mock-infected cells, fail to activate these gene expression programs. Taken together, these results suggest the following hypothesis we propose to address. First, unedited Alu RNAs are continuously synthesized and exist at high levels in cells. If unedited, Alu RNAs form dsRNAs that stimulate potentially pathogenic anti-viral responses. However, Alu RNAs are continuously A-to-I edited so they cannot form dsRNAs. In response to viral infection, this continuous cycle is rapidly disrupted by loss of A-to-I editing by ADAR allowing accumulation of unedited Alu dsRNAs and stimulation of downstream anti-viral host responses. It is tempting to speculate that the value to the host of this unique continuous cycle is to rapidly stimulate anti-viral and pro-inflammatory host responses by Alu dsRNAs in response to viral infection to prevent accumulation and spread of pathogenic viral particles. To explore this hypothesis, we propose to infect mf, DC, and NHBE with SARS-CoV-2 and follow kinetics of loss of A-to-I editing of endogenous Alu RNAs and host responses using RNA-seq and our computational pipelines. We will also determine if RNAs that stimulate host responses are of viral origin or are Alu dsRNAs. In aim II, we will investigate ability of unedited and edited Alu RNAs to stimulate anti-viral responses and employ siRNA-mediated knockdown of Alu RNAs to demonstrate a direct role of Alu RNAs in the host anti-viral response.",2022,2024,Vanderbilt University Medical Center,259500,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2022 +C21080,1K99AI166250-01,Functional and antigenic evolution of SARS-related coronaviruses,"PROJECT SUMMARY SARS-related coronaviruses (also known as sarbecoviruses) circulate in bat reservoirs, but two human spillovers in the past 20 years-SARS-CoV-1 in 2002 and SARS-CoV-2 in 2019-have caused globally devastating outbreaks. The emergence of SARS-CoV-2 from a previously unknown bat lineage highlights the pressing need to trace the evolutionary origins of viral properties that enable human spillover and develop therapeutic reagents that can broadly inhibit infection by diverse, potentially unsampled sarbecovirus lineages. Sarbecovirus zoonosis depends in part on the evolution of viruses to interact with ACE2 receptors on the surface of human and potential intermediate hosts' cells, mediated by the viral spike receptor-binding domain (RBD). The RBD is also a key component to therapeutic control of SARS-CoV-2 and presumably other sarbecoviruses, as it is the target of the most potently neutralizing antibodies, including those in clinical development and in polyclonal human sera. Although I and others have begun surveying the impacts of mutations within SARS-CoV-2 itself on important biochemical phenotypes including binding to ACE2 receptor and antiviral antibodies, these studies have only limited utility in understanding the broader evolution of sarbecovirus RBDs, which exhibit considerable divergence in sequence and function. To characterize sarbecovirus functional and antigenic evolution, I propose to combine high-throughput protein binding experiments with computational evolutionary analyses, functional virology, and biochemistry: 1. I will profile the ACE2-binding specificities of all known sarbecovirus RBDs and their evolutionary precursors. I hypothesize that the ability to bind ACE2, including the human ACE2 ortholog, is more evolutionarily and geographically widespread than previously appreciated. 2. I will systematically characterize how diverse RBD mutations affect ACE2-binding phenotypes. I hypothesize that human ACE2 binding is an easily evolvable trait in sarbecovirus lineages where it has not been previously considered. I also hypothesize that divergence among sarbecovirus lineages shifts the genetic and biochemical determinants of ACE2 binding over evolutionary time. 3. I will identify RBD epitopes that are susceptible to broad pan-sarbecovirus antibody binding. By determining the relationship between breadth and other antibody properties across RBD epitopes, I highlight key features to target in the design of next-generation pan-sarbecovirus vaccines and antibody therapeutics. Identification of the evolutionary and biochemical basis for key sarbecovirus features enhances viral surveillance and therapeutic development, preparing for or even preventing future sarbecovirus spillovers. The new experimental expertise, broader training and mentorship, and research systems developed in this work will enable me to achieve my goal of leading an academic lab studying protein evolution at the host-virus interface.",2022,2024,FRED HUTCHINSON CANCER CENTER,128574,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +C21081,1R21AI166292-01,SARS-CoV-2 N interactions with RNA and host cell cyclophilin-A,"PROJECT SUMMARY Coronaviruses (CoVs) have emerged as formidable human pathogens since their detection within human populations only 50 years ago, underlying the need to rapidly characterize their molecular mechanisms in order to thwart their infections through therapeutics. Seven CoVs that infect humans are known with a range of pathogenicity, which include the more recent virulent CoVs such as MERS, SARS-CoV-1 and SARS-CoV-2. CoVs comprise four structural proteins that includes the envelope (E), membrane (M), spike (S), and nucleocapsid (N) proteins. CoV N proteins perform numerous functions during the viral life-cycle that includes both packaging genomic RNA and manipulating the host cell machinery, making the N protein the most abundantly expressed viral protein during infection. However, the unique and diverse functions of CoV N proteins have made standard structural methods that address its molecular interactions difficult. For example, such difficulties include their promiscuity in RNA binding, engaging multiple binding sites simultaneously, and the presence of inherently dynamic regions thought to be critical for engaging RNA and host proteins. NMR offers a solution to such challenges, as multiple binding modes can be simultaneously characterized both dynamically and structurally and we have previously shown that the inherently dynamic regions within a CoV N protein (SARS-CoV-1) can be studied by NMR. Thus, the exploratory nature of this R21 proposal is to develop strategies aimed at elucidating the molecular details that underlie the SARS-CoV-2 N protein interactions with RNA (Aim 1) and host proteins (Aim 2). Based on our preliminary studies, we hypothesize that specific regions within the N protein have preferred RNA binding sites (Aim 1) and host cell cyclophilin-A binding sites (Aim 2). We will address these aims through the following: Aim 1) Determine how the SARS-CoV-2 N protein targets RNA. Biochemical and biophysical approaches that include NMR will be used to identify the high affinity binding sites of the N protein within sequences derived from genomic RNA and identify the associated dynamic and structural changes that occur upon complex formation. Aim 2) Determine how the SARS-CoV-2 N protein targets host cell cyclophilin-A. NMR will be used to determine whether the N protein targets the cyclophilin-A active site and whether the N protein is a substrate.",2022,2024,UNIVERSITY OF COLORADO DENVER,194375,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +C21082,1R21AI166743-01,Digital pathology for defining myeloid cell-mediated lung injury during acute SARS CoV-2 Infection in hamsters,"Project Summary Macrophages and neutrophils are implicated in SARS CoV-2 pathogenesis in people and non-human primates but their contribution to SARS CoV-2 pathology in the hamster model is poorly defined. We hypothesize that myeloid cells can be targeted therapeutically to improve COVID-19 outcomes and we will explore this in the hamster model of COVID-19 infection. The hamster model is a tractable small animal model for COVID-19 that models severe clinical disease in humans yet, variations in study design, tissue and time-points assessed limit cross-institutional comparison of results and result reproducibility. We propose that quantitative image analysis can be used to effectively monitor immune cell infiltrates and define mechanisms of disease progression in the hamster model, but pathologic correlates of clinical disease need to be established. More broadly, there is a need to standardize quantitative pathologic endpoints in animal models of SARS CoV-2 infection in order to benchmark study quality, improve cross-institutional comparison of data, validate cellular targets, and assess therapeutic efficacy such that potential drugs for SARS CoV-2 can rapidly advance. We will use quantitative image analysis to explore mechanisms of myeloid mediated tissue damage such as antibody dependent enhancement of disease (ADE) and the PI3K inflammatory pathway. Using the Syrian hamster model and digital pathology we will assess the relative contribution of myeloid cell populations to disease pathology in SARS CoV- 2 infection and explore mechanisms of myeloid-mediated lung damage. We will develop image analysis tools to quantify inflammatory infiltrates and define pathologic correlates of clinical disease in the hamster model of SARS CoV-2 infection. We will perform titration studies to establish pathologic endpoints that correlate with clinical disease and viral load to better understand vaccine and therapeutic outcomes in this model. We will also define mechanisms of myeloid-mediated tissue damage in SARS CoV-2 infected hamsters using an optimized image analysis toolset. We will explore subtherapeutic monoclonal Ab (MAb) treatment and non-protective levels of vaccine-induced neutralizing antibodies to establish pathologic metrics for assessing iADE and use a PI3K-γ inhibitor currently in Phase II clinical trials for solid tumors, to determine whether myeloid cell trafficking can be modulated by inhibiting the PI3K-γ pathway. Development of validated and standardized quantitative image analysis end-points that correlate with clinical and virologic control in hamsters will more rapidly advance pre- clinical drug and vaccine efficacy trials for development of SARS CoV-2 therapeutics and preventives. These tools can also be used to explore pathologic mechanisms of disease in COVID-19. 1",2022,2024,TUFTS UNIVERSITY BOSTON,247500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease models | Disease pathogenesis,2022 +C21083,1K25AI166040-01,Rapidly Adaptable and Mass-Producible Microscopic Chiplets for Minimally-Instrumented Respiratory Viral Screening,"Project Summary Objective: Respiratory viral infections affect millions of individuals each year. Conducting frequent widespread viral screening tests can curb outbreaks by quickly identifying infectious persons. Unfortunately, no screening diagnostic platform exists with the capacity to test hundreds of millions of people daily during a pandemic. This proposal is the first step in developing a novel viral screening test to fill this gap. The assay will consist of microscopic circuits containing field effect transistors with antigen-specific receptors that are sensitive to particular viruses. These chiplets - barely visible to the human eye - will be powered by light and will transmit data using a light emitting diode, such that a few can be mixed into an extracted sample and illuminated with a handheld device to yield immediate results. This diagnostic will be scalable and inexpensive; millions of tiny chiplets can be fabricated simultaneously. It will be minimally instrumented; an ordinary cellphone with a strobe flash and camera will interface with the chips. It will be flexible, rapidly adaptable, and multiplexable; receptors specific to different or emerging viruses could be immobilized on distinct circuits, allowing multiple diseases to be detected simultaneously in a single patient sample. This diagnostic will thus be unmatched as a mass producible, simple to use, adaptable, and high throughput tool for frequent and widespread virus screening. Specific aims: The proposed diagnostic will be developed by pursuing the following specific aims. 1. Integrate biological field effect transistors into the existing optical wireless integrated circuit platform. 2. Develop a multiplexed detection scheme for interacting with optical wireless integrated circuits. 3. Demonstrate the test's feasibility in a clinically relevant quantitative range using mock clinical specimens. Career development plan and career goals: Dr. Matthew Campbell (Ph.D., P.E.) is a postdoctoral researcher in the School of Engineering and Applied Science at the University of Pennsylvania, where his work is focused on fabricating microelectromechanical systems. The proposed K25 career development award will apply his nanofabrication skills toward biosensor development and extend his training and exposure into two new domains: (1) biomedical experimentation, and (2) medical biology. This proposal contains a cohesive mentorship and didactic strategy centered on these areas to accelerate his trajectory toward research independence. Completion of this multifaceted training plan will position Dr. Campbell with the cross-disciplinary skills and expertise necessary to become a leading investigator in the field of biomedical sensing diagnostics. Mentors and environment: Dr. Campbell is enthusiastically supported by the university and his strong mentoring team. His primary mentor is an expert in micromanufacturing (Prof. Igor Bargatin (Ph.D.)), and his co- mentors bring extensive experience in microscopic circuits (Prof. Marc Miskin (Ph.D.)), field effect transistor sensors (Prof. Charlie Johnson (Ph.D.) and Prof. Haim Bau (Ph.D.)), and viral respiratory tract infections (Prof. Ronald Collman (M.D.). This group will provide the ideal training situation for Dr. Campbell to develop this assay.",2022,2027,UNIVERSITY OF PENNSYLVANIA,114345,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +C21084,1R21AI166134-01,Molecular principles of anti-COVID-19 drug uptake by human nucleoside transporters,"Summary COVID-19 (coronavirus disease 2019) is a contagious upper respiratory disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, which features high morbidity and is rapidly spreading worldwide. The need to develop therapeutics against COVID-19 is urgent, and one route to shorten the time to an effective medicine is repurposing existing antiviral drugs or utilizing those in the pipeline. Three therapeutics that have shown initial promise in either pre-clinical or clinical settings are nucleoside-analog antivirals remdesivir, NHC (beta-D-N4-hydroxycytidine), and galidesivir. Currently, NHC and galidesivir are in clinical trials and remdesivir is approved for emergency use in U.S. The commonality between these drugs is that they are nucleoside analogs that target the SARS-CoV-2 RNA-dependent RNA polymerase. Because nucleosides are hydrophilic, specialized membrane transport proteins are required for their cellular uptake. In humans, two protein families mediate the selective membrane permeation of nucleosides: concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs). It is well established these nucleoside transporters control drug efficacies of many nucleoside-analog antiviral and anticancer therapeutics in a clinically relevant manner. Therefore, we reason that the cellular uptake of the aforementioned candidate COVID-19 therapeutics by human nucleoside transporters would prove critical to their antiviral efficacies. We aim to study the role of these transporters in the cellular uptake of these nucleoside antivirals by performing antiviral efficacy assays, structural studies of drug-transporter interactions, and in vitro transport assays. Structural and mechanistic studies of the interactions between potential COVID-19 antiviral drugs and human cellular transport proteins would uncover the molecular basis of antiviral drug cellular transport in humans. Such information would pave the way for the rational design of therapeutics with improved efficacies via enhanced drug disposition properties, and for personalized anti-COVID-19 treatments via drug-transporter pharmacogenomics.",2022,2024,DUKE UNIVERSITY,240020,Other,Unspecified,Unspecified,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +C21085,1R01MD016880-01,Increasing COVID-19 Vaccine Uptake among Latinos through a Targeted Clinical and Community-behavioral Intervention,"Project Summary/Abstract The United States currently has the highest COVID-19 infection and related mortality rates in the world. In California, Latinos account for the highest percent of COVID-19 cases (58.9%) and deaths (47.3%) and are disproportionately represented in occupations deemed as 'essential'. Latinos also suffer from higher rates of poverty and chronic disease which places them at greater risk of COVID-19 infection and related complications. In collaboration with Family Health Centers of SD (FHCSD) and working with Community Health Workers (aka, promotores/as), we will implement a multilevel intervention to increase COVID-19 vaccine completion rates and see faster vaccination uptake among Latinos. A total of 10 clinics will be randomized to either a Standard Clinical Practice consisting of standard clinic-based strategies to promote COVID-19 vaccine uptake among patients or a Multilevel Intervention consisting of an individualized/tailored intervention delivered by Health Educators working within the clinics plus a multi-component community intervention delivered by community promotores. This project will test the immediate and short-term effectiveness of the multilevel intervention to increase COVID- 19 vaccine uptake. In addition, we will test the effectiveness of the proposed intervention on long-term behavioral, mental, and physical health outcomes. Lastly, this project will assess implementation outcomes including program acceptability and feasibility by patients and clinic staff and community environment. This study aims to increase the uptake of completing the COVID-19 vaccine in a population that has exceptionally high rates of morbidity and mortality due to COVID-19. We will harness our research team's extensive experience in developing multi-level interventions working with Health Educators and promotores to promote behavior change among Latinos, and leverage a strong community-academic collaboration that maximizes community impact and sustainability. This research will lead to the development of sustainable and scalable community-academic models designed to respond quickly, efficiently, and effectively to both this existing and future public health threats.",2022,2025,SAN DIEGO STATE UNIVERSITY,633539,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2022 +C21086,1P01AI165066-01,Structural vaccinology guided development of a universal CoV vaccine utilizing nucleic acid delivered nanoparticles,"Project Summary In December 2019 a novel coronavirus, named sudden acute respiratory syndrome coronavirus-2 (SARS-CoV- 2). SARS-CoV-2 rapidly spread around the globe causing a pandemic disease termed coronavirus disease of 2019 (COVID-19). There have been more than 80 million infections and close to two million deaths from COVID- 19 to date. SARS-CoV-2 is the third beta coronavirus of zoonotic origin to cause human epidemics. It is similar to, but distinct from, Middle East respiratory syndrome coronavirus (MERS-CoV) and sudden acute respiratory syndrome virus-1 (SARS-CoV-1), both of which have caused outbreaks this century. While several candidate vaccines for SARS-CoV-2 have recently received emergency use authorization, the longevity of vaccine-induced responses, the continued emergency of mutation within SARS-CoV-2 strains, and the disproportionate morbidity and mortality among elderly patient populations present continued challenges to control of SARS-CoV-2. Thus, vaccine modalities which can address these challenges for SARS-CoV-2 vaccines and allow for targeting of multiple potentially pandemic coronaviruses simultaneously are greatly needed. Innovative vaccines which can develop broad immunity against known and newly emergent human coronavirus is a key goal in the field. The effects of antigen epitope diversity, density, valency, duration of antigen availability, and adjuvant- induced cytokine environment on the potency and breadth of vaccine-induced Reponses remains unclear. Nanoparticle vaccine formulations allow the ability to manipulate these variables. We have generated self- assembling synthetic DNA-launched nanoparticle vaccines (DLNPs) which displayed increased immunogenicity compared to matched synthetic DNA launched monomer vaccines or protein-in-adjuvant formulations. We determined that synthetic DNA launched nanoparticles increased both cellular and humoral responses. Recombinant nanoparticle vaccines are thought to mediate their increased immunogenicity by persisting in the lymph nodes for extended periods compared to protein antigens, promoting enhanced antigen presentation by follicular dendritic cells and increasing germinal center formation and humoral immunity. Cell-mediated responses to nanoparticle vaccines are less well understood but similar mechanisms may be at play. We will capitalize on the novel in vivo assembling synDLNP platform we have created to manipulate these variables and determine their effects on acute and long-term responses to CoV antigens in young and aged models.",2022,2025,WISTAR INSTITUTE,2626814,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2022 +C21087,1R01AG074710-01,The Care Ecosystem Response to COVID-19: Accelerating Research on Dementia Care that Meets the Needs of Caregivers and Persons with Dementia during COVID-19,"PROJECT SUMMARY/ABSTRACT Dementia causes substantial burdens for patients and caregivers, which have been exacerbated by the COVID- 19 pandemic. The current state of dementia care is inadequate to meet the needs of this growing, vulnerable population. Scalable, effective, and person-centered dementia care models that are aligned with value-based healthcare reforms are needed now. The Care Ecosystem is an accessible, remotely delivered team-based dementia care model, designed to add value for patients, providers and payers in complex organizational and reimbursement structures. Care is delivered via the phone and web by unlicensed Care Team Navigators, who are trained and supervised by a team of dementia specialists with nursing, social work, and pharmacy expertise. Care Protocols guide proactive, quality care that is documented in the electronic health record. The evidence base to date suggests that the Care Ecosystem improves outcomes important to people with dementia, caregivers, and payers when delivered in a controlled research environment, including reduced emergency department visits, higher quality of life for patients and lower caregiver depression. We propose a rapid pragmatic trial in 6 health systems serving geographically and culturally diverse populations. We will leverage technology, delivering care via the phone and web and using electronic health records to monitor quality improvements and evaluate outcomes while maximizing external validity. In Aim 1, we will use implementation science to identify the model adaptations, facilitators, and barriers to implementing and sustaining the Care Ecosystem during the COVID-19 pandemic. In Aim 2 we will use mixed methods to rigorously evaluate the effectiveness of the Care Ecosystem on outcomes important to patients, caregivers, healthcare providers, and health systems during the pandemic. In Aim 3, we will characterize the patient and caregiver factors associated with treatment benefit. This will include investigating effectiveness in underrepresented groups and elucidating unmet needs that will guide future development work. By simultaneously evaluating the real-world effectiveness and implementation strategies in diverse health systems, this project will bridge the science-practice gap in dementia care during an unprecedented time of heightened strain on family caregivers, healthcare providers and health systems. Furthermore, this work will pave the way for expanding access to high quality dementia care in the future, mitigating the negative impact of dementia on patients and their families across the nation.",2022,2025,University Of California-San Francisco,2908756,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Clinical characterisation and management | Research on Capacity Strengthening,"Supportive care, processes of care and management | Systemic/environmental components of capacity strengthening",2022 +C21088,1R01MH131248-01,Pragmatic RCT of a multi-level mechanistically informed community intervention to prevent the onset of behavioral health symptoms among socioeconomically disadvantaged pandemic affected children,"PROJECT SUMMARY/ABSTRACT The COVID-19 pandemic is having a profound impact on children globally, jeopardizing their sense of safety, security, and behavioral health. In addition to COVID-19, millions of children are still recovering from recent hurricanes that struck the southern the United States. Children exposed to climate-induced disasters (e.g. hurricanes) are at a significant risk for mental and behavioral health challenges. Coupled with an enduring pandemic, many of these children are disproportionately at risk for escalating mental health problems. Racial and ethnic minority children who live in socio-economically disadvantaged neighborhoods are among the most vulnerable during and after large-scale disasters. They are more likely experience high levels of social and material losses, displacement, and lack of access to mental and physical health services. Thus, there is a critical need for these children to received accessible, empirically supported preventative interventions to mitigate the onset of mental illness and behavioral health issues. Most post-disaster behavioral health interventions are designed to treat rather than prevent mental health conditions and are often inaccessible to racial and ethnic minority children living in socio-economically disadvantaged communities. The present study, therefore, seeks to examine the implementation and efficacy of the COVID-19 adaptation of a disaster focused empirically supported prevention intervention, the Journey of Hope (JoH), distributed by Save the Children, a humanitarian organization serving socio-economically disadvantaged and racial and ethnic minority children in communities dually impacted by COVID-19 and recent hurricanes that struck the Southern United States. The long-term goals of this study are to: (1) respond to the critical need of accessible behavioral health interventions designed to prevent and/or reduce COVID-19 related distress; and (2) provide an understanding on how a COVID-19 tailored prevention intervention mitigates behavioral health disparities among racial and ethnic minority children in high poverty settings who have been exposed to multiple large scale disasters. In a pragmatic randomized control trial with 800 children between 3-8th grade, we seek to: Aim 1: Evaluate the efficacy of the COVID-19 adapted JoH (JoH-C19) in preventing behavioral health and interpersonal problems among socio-economically disadvantaged and racial and ethnic minority children who have been exposed to multiple large-scale disasters relative to a healthy life-style attention control condition. Aim 2: Examine if hypothesized mechanisms of change variables (social connectedness, adaptive coping, self-efficacy) mediate intervention effects (JoH-C19 vs attention control) on child individual behavioral health and interpersonal outcomes. Aim 3: Assess the moderating impact of COVID-19 related stressors on behavioral health outcomes among children who participate in JoH-C19 versus the control condition. Aim 4: Explore implementation barriers, facilitators, and acceptability of the JoH-C19 within school and afterschool settings and delivered by community and school-based counselors.",2022,2026,UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN,776894,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Minority communities unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +C21089,3S06GM127983-04S1,Cherokee Nation Native AmericanResearch Center for Health,"PROJECT SUMMARY Through the RADx-UP program, the Cherokee Nation Community-Driven Program for Testing and Contact Tracing (Cherokee PROTECT) unites tribal, academic, and community partners under the leadership of Cherokee Nation (CN) to solve a dire need for COVID-19 testing, contact tracing, and culturally informed education in underserved and vulnerable rural populations. As of August 4, Cherokee Nation Health Services (CNHS) has confirmed >850 cases of COVID-19 in the tribal populations served across mainly rural northeastern Oklahoma. Community spread of COVID-19 exists throughout all 14 counties in the CN reservation, but with CN's limited capacity for community testing, screening, and contact tracing, the true impact of COVID-19 is unknown. Roughly 34% of American Indian/Alaska Native (AI/AN) adults aged 18-64 years are at risk of severe COVID-19 due to comorbidities, more than any other racial/ethnic group in the US. Five counties in CN are in the top 20% of US counties for the prevalence of adults at risk of severe COVID-19 due to underlying medical conditions; this vulnerability is compounded by high poverty rates and geographic barriers. People living in rural areas of CN may have to travel as many as 60 miles round-trip for viral testing. Most COVID-19 testing in CN to date has been conducted through CNHS, the largest tribally compacted health system in the US that serves all AI/AN people living within the CN reservation. Although CNHS accounts for approximately 8.5% of all IHS active user population and 38% of active user population of Oklahoma service area, not all tribal members residing in the reservation access CNHS, and therefore, may not be tested by CNHS. Other than CNHS clinics, 7 of 14 counties in this area have only one public testing site, and results may not be returned for 2-3 weeks. CNHS and its closely integrated CN Public Health program have an exemplary 20-year record of delivering public health interventions, including a groundbreaking Hepatitis C Virus elimination program with the University of Oklahoma Health Sciences Center, and ongoing projects with >40 rural K-12 schools. Through collaborative clinical research and molecular studies, CN and the Oklahoma Medical Research Foundation have identified new immune biomarkers in tribal populations. Drawing on these existing strengths and infrastructure, Cherokee PROTECT will (1) Build infrastructure and increase FDA-EUA COVID-19 viral and antibody testing for clinical care in CNHS; (2) Enable community-based COVID-19 testing, contact tracing, and education with CN Public Health; (3) Identify barriers and facilitators to COVID-19 testing in the CN reservation to inform a tailored educational campaign to increase testing and contact tracing, and decrease spread; and (4) Implement a rigorous evaluation to ensure quality improvement and sustainability.",2022,2023,CHEROKEE NATION,1317488,Human Populations,Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +C21090,1R01MH126693-01,Reducing COVID-related PTSD symptoms in Frontline Healthcare Workers through Trauma-Focused Treatment in Employee Assistance Programs,"Project Summary/Abstract Healthcare workers on the frontlines of the COVID-19 pandemic are experiencing unprecedented levels of stress and trauma exposure, resulting in exceptionally high rates (27-57%) of posttraumatic stress disorder (PTSD). Although Employee Assistance Programs (EAPs) have expanded their offerings to support healthcare workers during the pandemic, they lack the capacity to provide time-intensive first-line treatments for PTSD. To address this problem, the study team has adapted a standard first-line 12-session treatment into a brief, 4-6 session format (Prolonged Exposure for Primary Care; PE-PC) and demonstrated its efficacy in military service members. Given the rising tide of PTSD in frontline healthcare workers, there is an urgent need to test the effectiveness and subsequently implement PE-PC for this population by leveraging the existing resource of the healthcare system EAP. The long-term goal is to address COVID-19-related PTSD symptoms among healthcare workers and other vulnerable populations. The overall objective of this application is to demonstrate the effectiveness and identify barriers and facilitators to the implementation of PE-PC in healthcare system EAPs. The central hypothesis is that PE-PC will reduce COVID-19-related PTSD symptoms and improve functioning, compared to EAP Treatment as Usual (TAU). The rationale is that effectively treating COVID-19- related PTSD in the EAP setting is a scalable and cost-effective way to reduce healthcare worker distress and disability and will accrue downstream benefits to the healthcare organization and its patients. To accomplish the objective, this project will test the effectiveness of PE-PC, delivered by EAP counselors via telehealth, versus EAP TAU in 360 healthcare workers with PTSD at four southeast Michigan healthcare systems. This Hybrid Type 1 effectiveness-implementation trial will test the effectiveness of PE-PC and gather data regarding implementation through process evaluation and implementation mapping. The specific aims are: Specific Aim 1: Compare the effectiveness of PE-PC versus EAP TAU in reducing PTSD symptoms at 6-week (post- treatment), 3-, and 6-month follow-ups. Specific Aim 2: Compare the effectiveness of PE-PC versus EAP TAU in reducing burnout and improving job performance and functioning at 6-week, 3-, and 6-month follow-ups. Exploratory Aim 1: Confirm the mechanism and identify key mediators/moderators. Exploratory Aim 2: Conduct cost-effectiveness analysis. Exploratory Aim 3: Prepare for future implementation by conducting process evaluation and implementation mapping. This strategy will yield an implementation strategy that is targeted to address EAP-specific implementation barriers. This project is significant because it will contribute to the field a point-of-care intervention for frontline HCWs with COVID-19 related PTSD, thus improving clinical practice for this vulnerable population and increasing preparedness for future public health emergencies. This proposal is innovative because it will it will shift delivery of efficacious PTSD treatment from lengthy care in a traditional specialty care setting to brief treatment with a telehealth option in a frontline community setting.",2022,2026,UNIVERSITY OF MICHIGAN AT ANN ARBOR,779420,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Emergency Responders | Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2022 +C21091,1R21AI161501-01,Elucidating Airborne SARS-CoV-2 Infectivity at Single Aerosol Resolution,"PROJECT SUMMARY In this emergency R21 effort we propose to implement a set of novel studies designed to improve our fundamental understanding of SARS-CoV-2 aerobiology. Through a combination of theoretical, experimental, and epidemiological data, there is emerging consensus that respiratory aerosols play a primary role in the transmission of COVID-19. However, despite the importance of understanding the fundamental mechanisms involved in the airborne transmission route, a number of basic questions central to SARS-CoV-2 aerobiology remain unanswered. In particular, the distribution of SARS-CoV-2 particles within different aerosol size populations has not yet been studied in detail, nor is there data available to predict the viability and infectivity of individual airborne virus particles within different aerosol populations. Furthermore, it is not currently known whether the virus tends to be uniformly distributed within a given aerosol population or clustered within a small number of aerosol droplets, an essential question for understanding the quantum of infection for COVID-19 transmission. To address these challenges, we propose a novel analytical approach combining efficient sampling of exhaled breath, high resolution fractionation of aerosol ensembles, and coupled analysis of inactive and infective virus particles within the collected aerosol fractions through a combination of RT-PCR and viral plaque assays. Significantly, aerosol fractionation will be performed using an Aerodynamic Aerosol Classifier as a unique technology for isolating monodisperse aerosol populations. In addition, a new technique for discretizing the collected aerosol particles will be implemented using a thermo-responsive hydrogel for aerosol deposition, allowing the particles to be delivered to cell culture while remaining spatially isolated and elucidating virus distribution and clustering within a given size fraction. The combined data sets resulting from the proposed studies will provide a first view of the distribution and conformation of SARS-CoV-2 within respiratory aerosols, and the relationships between aerosol properties (size, virus content, virus distribution, and clustering) and downstream infectivity. We anticipate that the improved understanding of aerosolized virus infectivity emerging from these studies will illuminate fundamental aspects of COVID-19 airborne transmission and allow us to identify the quantum of infection associated with SARS-CoV-2, thus supporting accurate modeling of transmission dynamics and guiding improved recommendations for PPE, room ventilation, and sanitation protocols to enhance intervention and minimize transmission of the virus.",2022,2024,The University of Maryland - College Park,414425,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,Americas,,,,United States of America,United States of America,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease transmission dynamics,2022 +P21093,MC_UU_00034/9,COVID-19 Drug-Screening and Resistance Hub (CRUSH),"Working in collaboration with LifeArc, MRC and Drug Discovery Unit (DDU) at the University of Dundee, the CVR created a translational hub for antiviral drug screening and resistance development. CRUSH is a fully integrated single-site hub with biocontainment facilities and expertise dedicated to accelerating antiviral therapeutic discovery for SARS-CoV-2 and other high consequence viruses requiring BSL2 (CL2) & BSL3 (CL3) containment. It is a one-stop facility with capabilities to perform medium- to high-throughput screens of antivirals, serology/virus neutralisation assays, hit validations in primary cultures and against panels of variant viruses, kinetic assays, assays to determine genetic barrier to resistance to selected hits, real-time monitoring of emerging mutations, and finally efficacy evaluations in pre-clinical small animal models. We will develop the newly established CRUSH platform as a vehicle for translation in the CVR and to boost our engagement with industry, but also to interface with the CVR’s Preparedness Platform. Established with funding from LifeArc and the MRC, CRUSH is a translational hub, facilitating the CVR’s interface with industry. It is a one-stop, self-sustaining facility designed to aid pre-clinical development of antiviral drugs against SARS-CoV-2 and other viruses requiring CL3 containment. Over the next quinquennium, we will further develop high-throughput assays that can be performed at both CL2 and CL3 levels to increase the capacity of the facility, and the use of experimental animal models. Specifically, CRUSH conducts drug screening and neutralisation assays for SARS-CoV-2 including alpha, beta, gamma, delta, omicron variants and new variants as they arise. New assays have been developed for monkeypox (Mpox) virus and influenza A. Other viral targets currently included under development for screening services include seasonal coronaviruses, influenza A/B, RSV, enteroviruses, rotavirus and arboviruses. CRUSH will support the implementation of a quality management system and integration of laboratory information management system (LIMS) encompassing an ELN/Bio-registry, to support data integrity and management. Additionally, the optimisation and development of a high-throughput screening system and completion/publication of in vivo models and exemplar studies. Our animal licence has now been extended to encompass transmission studies, vaccines/immunomodulators and flow cytometry and we intend to extend this further to include Mpox virus and anti-viral drug evaluation. The long-term goal of CRUSH is to create a stable and sustainable resource for the UK’s academic and industrial community to help accelerate drug discovery for any known or novel high consequence virus requiring high containment facilities.",,2028,University of Glasgow,446400,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae | Orthomyxoviridae | Poxviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Mpox | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2023 +P21094,MC_UU_00034/6,Preparedness Platform,"Emerging viruses pose a significant threat to the health and wellbeing of the UK population. Increased contact between humans and zoonotic reservoirs due to anthropogenic change means that the likelihood of outbreaks is increasing. Strategies will be required to reduce the risk of outbreaks at source and to contain them once they are established. In the Preparedness platform, we will build on infrastructure developed during our research response to the COVID-19 pandemic and on strong UK and international partnerships, aiming better to understand, prevent, detect and respond to viral threats to human health. The aims of this framework have been developed in consultation with colleagues in the UK Health Security Agency (UKHSA) at Porton (Rare and Imported Pathogens Laboratory) and Colindale, Public Health Scotland (PHS) and our international partners in Uganda and Malawi to identify key areas that require research innovation and development. Activities will be organised around three central themes that require innovative research-based approaches for enhanced surveillance and preparedness, employing emerging technologies that align with the strengths of the CVR. The platform is designed to be flexible, to integrate core funded activities and externally funded projects that benefit from access to the underpinning infrastructure that includes expertise in genomics and bioinformatics, molecular virologists, clinicians embedded within the NHS, staff with joint appointments with the UK public health agencies, a serology laboratory, an outbreak biorepository, CL3 facilities and data linkage systems. This represents an unrivalled combination of resources and expertise. We have recently demonstrated how we can rapidly pivot to address emerging viruses and aim to build on this experience.",,2028,University of Glasgow,3703880,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,Epidemiological studies,,2023 +P21096,MR/X018563/1,Pre-symptomatic asymptomatic MonkEypox (PRIME) study,"The aim is to improve understanding of monkeypox (MPX) transmission by identifying the proportion of sexual contacts of MPX cases in whom MPX virus can be detected and the timing of detection in relation to any associated symptoms, to inform intervention strategies and modelling of disease spread. In this prospective cohort study, identified sexual contacts of confirmed MPX cases as well as individuals who self-report sexual contact with a confirmed MPX case will be asked to undertake self-sampling of nose and throat swabs, ano-genital swabs, and or urine samples depending on participant characteristics and the nature of sexual contact with the index case. Optional serologic testing will be performed by self-sampling at baseline and one month after the last exposure to a MPX case. Informed consent will be obtained and all results will be fed back to individual participants. The primary objective is to estimate the proportion of secondary MPX cases who develop pre-symptomatic or asymptomatic MPX infection, defined as detectable viral DNA at any body site before the onset of symptoms or in the absence of symptoms, respectively. This will be achieved by PCR testing of swabs from nose and throat swabs, ano-genital swabs and/or urine tests at two intervals until 21 days following last sexual exposure with a confirmed MPX case, and optional serology testing at baseline and one month after the end of the first participants' exposure to a MPX case. Secondary objectives are to: a) Estimate the secondary attack rate (SAR) of MPX infection in a defined cohort of known sexual contacts of confirmed cases. SAR is defined as the proportion of sexual contacts of MPX cases who have detectable viral DNA at any body site and/or seropositivity b) Estimate the vaccine effectiveness (VE) of smallpox vaccination for asymptomatic infection c) Estimate the incubation period before development of, and the duration of, asymptomatic and pre-symptomatic viral shedding",,2024,UK Health Security Agency,1260039.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission.,United Kingdom,,"Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation",Disease transmission dynamics | Disease surveillance & mapping | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity,2022 +P21097,MR/W025590/1,Restriction of DNA viruses by TRIM5a and ZAP / TRIM25 / KHNYN: mechanisms of restriction and viral evasion,"The host restriction factors TRIM5a, ZAP, TRIM25 and KHNYN provide defense against RNA viruses. For instance, TRIM5a provides protection against different retroviruses, including HIV. Proteins ZAP, TRIM25 and KHNYN, which show some functional interdependence, are also active against RNA viruses with CpG rich genomes and recently, ZAP and TRIM25 were shown to also restrict human cytomegalovirus (HCMV). We discovered that vaccinia virus (VACV) infection induce degradation of all 4 cellular proteins, and so hypothesised that they may have anti-VACV activity. This hypothesis was proved correct, for cells lacking TRIM5a, ZAP, TRIM25 or KHNYN individually, supported enhanced VACV replication, showing these proteins do provide defense against this large DNA virus. Like HIV, VACV virions also package cyclophilin A and VACV replication is inhibited by cyclosporine A in a TRIM5-dependent way. Loss of TRIM5a also enhanced herpes simplex virus (HSV) 1 replication. The project will investigate how these host proteins restrict VACV replication and how VACV evades such restriction. What viral proteins do they bind to? At what stage is virus replication restricted? Is this a direct effect following recognition of specific virus components, or indirect, by activation of the innate immunity by these restriction factors? We will also test if these host proteins can restrict the replication of other dsDNA viruses, such as HSV-1 and HCMV, and, for TRIM5a, monkeypox virus and variola virus. In parallel, the VACV protein(s) that induce the degradation of these cellular proteins will be identified, where not known already, and then their mechanism(s) of action will be studied. Can they act independently? Since the degradation of these cellular proteins is proteasome-dependent, it suggests these proteins may be ubiquitylated by E3 ubiquitin ligases and thereby marked for destruction. Which E3 ligases or other factors are involved?",,2025,University of Oxford,797341.35,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21098,MR/X020258/1,MRC Centre for Global Infectious Disease Analysis (MRC GIDA),"The COVID-19 pandemic has highlighted the threat that infectious diseases pose to societies whilst the rapid global spread of monkeypox, the identification of polio in the UK and US, and the emergence of Marburg viral haemorrhagic fever in Ghana are timely reminders of the challenges that lay ahead. Over the last 15 years, the MRC Centre for Global Infectious Disease Analysis has been at the forefront of the development and application of data analysis and modelling across a wide range of pathogens. A key feature of our approach is our close links with public health agencies in the UK and internationally, enabling rapid translation of scientific insights into actionable public health support. During this award, we aim to catalyse our inter-disciplinary approach across four research-based themes: a) Preparedness and Response to Emerging Threats: Building the epidemiological tools required nationally and internationally to respond to new threats. b) Global Health Analytics: Supporting strategies to control and eliminate endemic diseases. c) Vaccines and Therapeutics: Supporting the development pipeline for new products and evaluating the retrospective and prospective impact of existing products in reducing disease burden. d) Pathogen Genomic Epidemiology: Developing genomics data to support better surveillance of emerging threats and to inform vaccine development, alongside analytical methods that integrate genomic and epidemiological data to inform public health policy. Through three underpinning pillars - research software engineering, translation and communication (including a dedicated Translational Modelling Hub) and training and capacity strengthening - we will enable rapid communication and uptake of our outputs to external partners - including the academic community, public health agencies and wider society.",,2026,Imperial College London,3659554.08,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Unspecified,Not applicable,,,,,,,,COVID-19 | Mpox | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Data Management and Data Sharing,,,United Kingdom,,"Epidemiological studies | Infection prevention and control | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2023 +P21099,2020/04705-2,Diagnostic and prognostic study of SARS-CoV-2 infection and influenza virus,"Introduction: The epidemics caused by the Influenza virus are recognized for their great impact on public health. The identification of a new coronavirus strain (SARS-CoV-2) with pandemic spread has brought new challenges for diagnosis, control and therapy. The rapid and low-cost diagnosis of SARS-CoV-2 and Influenza infections may allow the adoption of measures to control transmissibility both in the environment of Health Units and isolation from social contact in the community. The early identification of patients with a higher risk of death also allows a targeted therapeutic approach with ventilatory support measures and the use of specific antivirals against these two viruses. The understanding of pathophysiological mechanisms related to the coagulation cascade, involved in the severe forms of involvement by respiratory viruses, proposed in this project, may lead to the development of new therapeutic possibilities in order to reduce the high lethality of this serious clinical situation. Objective: 1) Development of a method for rapid and low-cost diagnosis of SARS-CoV-2 and Influenza virus infections; 2) study of early prognostic factors in patients diagnosed with SARS-CoV-2 infection and Influenza virus; 3) Study of platelet aggregation levels by Multiplate-ADP and coagulation in hospitalized patients due to respiratory distress. Method: 4 groups will be compared: SARS-CoV-2 infection patients, Influenza virus infection patients, influenza syndrome patients with negative tests for COVID-19 / Influenza virus and healthy controls. Patients with suspected flu-like symptoms (fever accompanied by one of the following symptoms: cough, sore throat, runny nose, frontal headache with onset of symptoms in the last 7 days) will be enrolled in 2 public referral hospitals. Exclusion criteria: Age below 18 years. The healthy control group will consist of 50 volunteer health care professionals paired by sex and age to the group of patients with SARS-CoV-2 infection. Peripheral blood, skin imprint and saliva samples will be collected from all individuals included in the study. Those who require hospitalization and present criteria for severe acute respiratory syndrome (SARS) will also be collected second and third samples of non-invasive specimens (skin imprint and saliva) 3 and 7 days after inclusion. Nasal flush will be collected for diagnosis of Influenza virus and SARS-CoV-2 infection by the protocol only for those who do not perform these tests through the hospital routine. All samples will be sent for storage (- 80C) at the Virology Laboratory of USP's Institute of Tropical Medicine and UNICAMP's Innovare Laboratory. Metabolites will be studied by plasma mass spectrometry, skin and saliva imprint and analyzed by artificial intelligence. The diagnosis of infection by Influenza virus or SARS-CoV-2 will be considered positive (gold standard) by positive molecular biology test in a nasal wash sample. Patients' prognosis will be assessed by the following outcomes: length of hospital stay, need for dialysis, need for orotracheal intubation or hospital death. Platelet aggregability will be studied using the Multiplate-TRAP and Multiplate-ASPI methods, reticulated platelet levels (young), mean platelet volume (MPV), P-selectin, D-dimer, PAI-1, Fibrinogen, Tromboxane, Tempo activated partial thromboplastin (PTTa), prothrombin time (TP); Type B natriuretric peptide (BNP); Ultrasensitive troponin, peak glycemia during hospitalization, lipid profile when hospitalized.",,2022,Heart Institute of the Hospital das Clínicas of FMUSP,35023.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Volunteers,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP),Brazil,Americas,Americas,,,,,Brazil,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity,2020 +P21106,222286,"Investigations into assembly, egress and virus-host interactions of Oropouche Virus","Tri-segmented bunyaviruses, which includes Rift valley fever virus and Oropouche virus (OROV), are responsible for a variety of human diseases ranging from self-limiting symptoms such as acute febrile illness, to lethal encephalitis and haemorrhagic fever. OROV is the first example of a virus shown to recruit endosomal sorting complex required for transport (ESCRT) components to virus assembly sites in the Golgi, through unclear mechanisms. During this project, I will develop virus-like particle assays to determine whether ESCRT recruitment is conserved across representative tri-segmented bunyavirus families. Once this has been established, I will investigate the molecular mechanisms that drive ESCRT recruitment to sites of bunyavirus assembly. I will do this by employing a range of proteomic approaches, that will utilise exogenously expressed bunyavirus envelope glycoproteins to identify potential interaction partners that are involved in ESCRT recruitment. Finally, I will conduct experiments using live OROV in collaborative research trips to Brazil, to understand how the virus changes the proteome of the cell during infection using a variety OROV mutants. These studies will elucidate a potentially novel mechanism of ESCRT recruitment during virus assembly and provide detailed understanding of bunyavirus-host interactions. Such new insights into bunyavirus infections may aid in development of antivirals.",,2023,University of Cambridge,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21113,MR/T02996X/1,Responding to the challenge of MERS-CoV: Development and testing of interventions to reduce risk among Bedouin populations in Southern Jordan,"Building on a successful GCRF Foundation Award, we aim to: i) Address knowledge gaps required to inform future vaccination strategies for MERS-CoV, ii) Develop and implement contextualized behavioural public health interventions to mitigate risk of MERS-CoV infection and iii) Build capacity for research, surveillance and control activities targeted at MERS-CoV. Two parallel longitudinal studies of camel owning households and their camel herds, together with an ethnographic survey, will be conducted in southern Jordan (Ma'an and Aqaba governorates). These studies will address knowledge gaps identified through the Foundation Award as important to inform future vaccination strategies such as who should be targeted for vaccination and the sociocultural issues, including vaccine acceptability, that are likely to be faced. Appropriate hygiene education interventions will be introduced as part of a randomized pilot feasibility trial in which half of the households will be randomly selected at month 18th of the project, with the other half remaining as 'control arm' during the following 6 months. Primary outcomes of the trial will be obtained from interviews on acceptability, perceived difficulty in implementing together with reported and observed behaviour related to avoiding camel oral and nasal secretions. Secondary outcomes will be based on serology in humans and camels in those having had the intervention in first half of year two compared to those who have not yet had the intervention. We will exploit opportunities for capacity building through grass-roots and higher-level workshops and engagement activities with the support of Jordan's Royal Scientific Society and US NIH. The importance , timeliness and opportunity of this project resides on the global public health threat posed by MERS-CoV, with Jordan as one of its epicenters, and the work carried out with the Foundation Award, which has generated knowledge and conditions that allow piloting of interventions.",,2024,Royal Veterinary College,2910716.88,Animals | Human Populations | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Rural Population/Setting,Unspecified | Not applicable,Other | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Animal source and routes of transmission | Vaccine/Therapeutic/ treatment hesitancy | Individual level capacity strengthening,2021 +P21117,2133763,URoL:EN Converging on the Rules of Emergence for Preventing Land Use-Induced Spillover,"Conceptually, land use change is recognized as a primary driver of zoonotic pathogen spillover from wildlife to human populations. However, the mechanisms by which land use change triggers the cascade of events that lead to spillover are little studied and have never been investigated from the perspective of a convergent, emerging network. In this project an interdisciplinary team will use convergent biological, computational, and social science approaches to identify the rules of life for land use-induced spillover. They will explore how land use change drives spillover of bat-borne Hendra and Nipah virus, which are World Health Organization priority-pathogens with epidemic and pandemic potential. This research will address the multiple scales of complexity that drive zoonotic spillover, and interactions among global climate change, local land use changes, and the human motivations and behaviors that lead to spillover. It will provide substantive insight into the mechanisms of spillover to inform the prevention of future pandemics from bat-derived viruses. The researchers will test existing assumptions and develop new theories and concepts to understand how human health and well-being is connected to the health of landscapes. Resulting insights could include how to break the land use-induced spillover network via ecological action (e.g., habitat restoration), economic incentives, and proactive actions rather than reactive social responses to pandemics. Understanding the emerging network of land use-induced spillover that leads to global emergencies such as the COVID-19 pandemic has tremendous societal relevance. The project will engage a diverse team of researchers and train four graduate students and three postdoctoral scholars, that encompass multiple scientific disciplines.

Land use change is a global phenomenon that is accelerating as human activity expands worldwide. This project will address the fundamental components of how land use change drives pathogen spillover into the human population, for emerging bat henipaviruses. The research will address three convergent questions: 1. Emergence: How does loss of habitat through deforestation interact with climatic cycles to trigger the chain of events that lead to viral spillover? 2. Network operations: How do environmental, biotic, human-engineered, and social systems interact to catalyze viral spillover? 3. Prevention or mitigation: How can viral spillover be prevented and mitigated by a convergent approach to ecological, socio-economic, and human-centric interventions to manage and communicate the risk of spillover? Researchers will study the interactions among environmental, ecological, sociological, and economic drivers of land use decisions, and the effects of such decisions on pathogen shedding from bats and zoonotic contacts between bats and spillover hosts. They will develop the knowledge and risk communication strategies needed to change human responses from reactive to proactive, to disrupt the negative cascades of land use-induced spillover networks and prevent future spillover events.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2027,Montana State University,2940810,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae | Novel Pathogen,,,,,,,,,Nipah and henipaviral disease | Hendra virus infection | Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology,2022 +P21130,221539,LASCOPE extension,"The “Lassa fever Clinical Course and Prognostic factors (LASCOPE)” project is a prospective cohort study of patients with acute symptomatic Lassa fever (LF) hospitalized in dedicated treatment centers in Nigeria. The patients have access, free of charge, to reliable molecular diagnosis of LF, ribavirin therapy and an improved standard of supportive care including renal replacement therapy. This study aims at producing up to date data on LF disease presentation and course, management, outcomes and factors associated to fatality. The data produced by the LASCOPE study will inform the design of future trials evaluating innovative therapeutic strategies for LF, as well as the development of updated guidelines for the management of patients with LF. Lastly, this project will contribute to the development of clinical research capacities in the participating sites and put them in position to conduct future therapeutic and vaccine trials for LF.",,2020,University of Oxford,163793.7,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Unspecified,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P21136,2031851,RAPID: Ethical Decision-Making about Conducting Essential Research in a Pandemic: Experiences of Principal Investigators and Research Personnel,"The COVID-19 pandemic has confronted researchers with unprecedented challenges. One of these challenges is the need to determine whether ongoing or new research projects are essential to conduct in-person during the crisis, and if so, which research personnel should conduct this research. Such decisions have been made all the more difficult by the challenges that plague them, including extreme time pressures, insufficient or vague guidance, competing personal and professional trade-offs, and uncertain ramifications for those affected by these decisions. A thorough understanding of the ethical and practical dimensions of these decisions is needed to help researchers and institutional officials better prepare for managing the scientific workforce during future crises. This project aims to understand how principal investigators have made these decisions during the current pandemic and identify the factors in their environments that shaped their decision-making, and how these decisions impact research personnel in their lab (e.g., graduate students, postdocs, technicians, staff scientists). Data from this project can help improve understanding about how principal investigators might approach challenging decision-making during similar future situations and how research personnel perceive and are affected by these decisions. Fostering enhanced awareness of and deepened appreciation for the unique challenges such emergencies pose to essential researchers will be valuable for researchers and the broader community that benefits from their work.

This project addresses two primary research questions: 1) what ethical considerations and practical challenges shape principal investigators? decision-making about whether and how to conduct in-person research projects during the COVID-19 pandemic?, and 2) how do research personnel ethically appraise their PI?s decisions and decision processes in light of their relationship and the context of the pandemic? Data collection will proceed using a mixed-methods approach to synthesize quantitative survey-based information from principal investigators and research personnel and interviews with select researchers, graduate students, and research staff. Initial surveys will be completed by hundreds of NSF- and NIH-funded scientists and research assistants, and follow-up interviews will be conducted with select participants. Data will then be synthesized, analyzed, and interpreted. Findings will be disseminated widely to benefit researchers in future emergencies. Answering these questions contributes to the research on ethical decision-making, ethical research cultures, research leadership, and pandemic policy-making.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2021,Washington University,199388,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Eastern Mediterranean,,,,,United States of America,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues in Clinical and Health System Decision-Making,2020 +P21147,2031703,RAPID: A comparison of the 1918 influenza pandemic and COVID-19 in Missouri: implications for current mitigation strategies in rural versus urban locations,"Social, Behavioral and Economic Sciences - This RAPID project will compare epidemic patterns and Missouri residents? responses in the 1918 influenza pandemic to those occurring at present during the COVID-19 pandemic, with primary attention paid to urban-rural differences. The research will increase understanding of how life situations in urban versus rural settings affect epidemic disease experiences and will provide knowledge of important community characteristics that put residents at greater risk during the current pandemic. The study will also shed light on which characteristics of a region have been stable over long periods of time and which are aspects of modern life and perhaps more malleable. The research is therefore time-sensitive because the investigators will expeditiously communicate project findings relevant to the current pandemic to the Missouri Department of Health and Senior Services. In addition, this project will provide student training in data collection and first-hand experience in conducting research to help deal with an unforeseen and serious public health event.

A new coronavirus, SARS-CoV-2, to which humans possess little underlying immunity, has been spreading throughout the globe. In this pandemic setting, rural regions may face challenges that are not present in urban areas. As there is currently no vaccine, it is critical to devise effective strategies quickly, to protect rural regions from echo waves of the virus that may circulate over the next few years. The world experienced a similar situation in 1918-19 when a new, lethal strain of influenza began to infect humans. Although there are significant differences between these two pandemics, the viruses have similar modes of transmission and overall impacts on human communities. Understanding the experiences and responses of rural citizens to these two pandemics provides important insights that may lead to new public health strategies that are more tailored to the needs of rural residents during major disease outbreaks. The project involves in-depth comparative analysis of mortality and morbidity patterns during the 1918 influenza pandemic and the present COVID-19 pandemic in the state of Missouri. Analysis will focus on data aggregated at the county level and will determine county characteristics (e.g., population density, number of hospitals, household composition, proximity to large urban area, ethnic composition, mobility patterns) that are associated with death and/or illness rates during the two pandemics. Historical data from the Missouri 1918 influenza pandemic will be examined to identify control strategies used in different counties during the pandemic, determine their effectiveness, and assess whether they would be of use during the present pandemic. This in turn can aid in the development of potential strategies that public health authorities can add to the arsenal already being used in rural counties.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2021,University of Missouri-Columbia,146794,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,H1,H1N1,,,,,,,COVID-19 | Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P21148,MR/V009761/1,"Mathematical modeling and adaptive control to inform real time decision making for the COVID-19 pandemic at the local, regional and national scale","emergence of a novel strain of coronavirus in the city of Wuhan in China resulted in a global pandemic and the implementation of social distancing measures in a significant number of countries around the world in order to reduce the risk to the most vulnerable members of society. The first case of infection in the UK was reported on 31st January 2020 and with cases continuing to rise, the country was put into lockdown on 23rd March in an effort to reduce the spread of disease. Throughout the epidemic in the UK, mathematical models (including predictions from Warwick) have been used to provide support to the government and to guide decision making. However, these models are typically required to repeatedly produce new outputs as more data emerges on a daily basis on cases and deaths, and there is a need to investigate how the predictions are likely to change as more data become available. This project will develop methodology that will allow for robust parameter inference of the Warwick model, which is already being used for UK-decision support. We will enhance our real time model fitting, incorporating up to date information on cases and outcomes, and use this framework to determine multi-phase adaptive control policies, with a focus upon optimal timing of relaxation and tightening of social distancing measures, that should be implemented to mitigate future infection waves. Our results will be communicated directly to the scientific pandemic influenza modelling group that advises the UK government.",,2021,University of Warwick,303913.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Data Management and Data Sharing,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P21153,222624,"Ready2Respond, a public-private collaborating platform to address pandemic preparedness gaps in lower income countries","Early 2019, a group of global health leaders with expertise in influenza, vaccinology and pandemic preparedness convened in London, for a Wellcome Trust-supported “Shaping Meeting to explore the value of a coordinated work plan for epidemic and pandemic influenza vaccine preparedness.” Ready2Respond was formed as a global collaboration of partners committed to enhancing lower income countries’ readiness to respond against influenza and respiratory viral pandemics. With a Secretariat established at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza preparedness, these priorities now include COVID-19. Three Expert Working Groups will design and execute cross-collaborative projects within three strategic priorities. - Burden of Disease - Risk Communication and Community Engagement - Vaccine Access Ready2Respond seeks an initial grant from the Wellcome Trust of US$ $196,650. This initial grant will allow to: - retain a Director, tasked with developing a comprehensive action plan with potential projects to start in 2021. - execute a mapping study of organizations and agencies working on global seasonal and/or pandemic vaccine preparedness to ensure the relevance of Ready2Respond’s mission and activities in the preparedness ecosystem. - support communication activities to secure funds for identified projects from potential partner organizations.",,2021,Task Force for Global Health,196650,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,Wellcome Trust,United Kingdom,Europe,,,,,,,,"Research on Capacity Strengthening | Policies for public health, disease control & community resilience",Institutional level capacity strengthening | Communication,2021 +P21154,101001521,Controlling Influenza A Virus Liquid Organelles (LOFlu),"The world health organization monitors viral infections worldwide with the aim to coordinate strategies to control viral outbreaks. The on-demand development of vaccines or antibody treatment does not confer a first line of defense against unpredictable infections caused by new viruses in humans such as pandemic influenza, corona or Ebola viruses, and new approaches are needed. We propose to investigate the fundamental basis of novel host-pathogen interactions in influenza A virus (IAV) infection that may define new antiviral strategies. We discovered that the important pathogen IAV induces the intracellular assembly of viral inclusions that behave like liquid organelles. IAV inclusions serve as assembly sites for the IAV segmented genome, a key step in the viral lifecycle. We now find that the maintenance of the liquid character of IAV inclusions is essential for viral replication. As we identified some of the host and viral components of IAV inclusions, we now have the tools to interrogate how specific interactions and cellular processes result in phase-separated compartments. We aim to learn how the function of IAV inclusions is related to their material state and investigate the potential of imposing phase transitions in an organism to limit IAV infection. Phase separation provides a novel conceptual framework to tackle how viruses exploit cells to organize viral reactions in space and in time. It also provides alternative principles for exploring aspects of the IAV lifecycle not yet fully understood, including how influenza epidemic and pandemic genomes assemble. Taken together, we propose a new, integrated approach for studying phase separated phenomena, from the molecular to the organismal level, that will bring a deeper understanding and control to viral infections. Our work will also be of relevance to other fields of biomedicine, including in the science of soft matter that is involved in neurodegenerative diseases and some cancers.",,2026,Calouste Gulbenkian Foundation,3358192.5,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,,,,,Portugal,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21155,P02960,"SBIR Phase I: IM3UNE: A Platform for Integrated Monitoring, Mapping, Modeling and Understanding of Novel Epidemics Like COVID-19","The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to assist with preparedness and decision-making for situations like the COVID-19 pandemic. This health crisis has been exacerbated by a lack of real-time information or predictive information about the extent, location, and spread of the disease. This Phase I project ingests data streams from government agencies, healthcare providers, and the general public, returning real-time, actionable information to assist in guiding a broad and coordinated response. While this platform is particularly relevant in the COVID-19 pandemic, it is disease agnostic, and will have utility for seasonal influenza and other infectious diseases, positively impacting public health.

This Small Business Innovation Research (SBIR) Phase I project will create a platform aimed at providing real-time identification of infectious disease outbreaks and predictions of disease spread, with an initial focus on COVID-19. Among the gaps in the response to the COVID-19 pandemic is capability to accurately track the magnitude, location, and spread of infectious agents. This project aims to assess and demonstrate the value of leveraging multiple modalities and sources of data for early detection and prediction of disease outbreaks, with focus on COVID-19. The approach will combine data fusion methods and epidemiological modeling approaches with continual input from subject matter experts in an effort to generate actionable information and predictive models related to disease spread. A variety of data streams providing information on disease incidence, transportation data, and sub-population interaction data will be used to construct progressively more sophisticated SEIR models. These efforts will result in an improved understanding of the utility and applicability of various data streams to epidemiological monitoring and forecasting, as well as platform for users of various levels of technical expertise.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2021,GEOMETRIC DATA ANALYTICS,255631,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2020 +P21159,3UL1TR002556-04S1,Convalescent Plasma to Limit Coronavirus Associated Complications: A Randomized Blinded Phase 2 Study Comparing the Efficacy and Safety of Anti-SARS-CoV-2 Plasma to Placebo in COVID-19 hospitalized pa,"Abstract: There are not any scientifically proven or approved therapies for COVID-19. Convalescent plasma (CP), whichis plasma that is obtained from people who have recovered from COVID-19, contains antibodies to SARS-CoV-2, the virus that causes this disease. CP has a long and storied history of improving symptoms and mortalityfrom other pandemic diseases, such as 1918 and 2009 influenza and SARS, as well as a myriad of other toxin-mediated and infectious diseases. Thus, CP is a rationally based and readily available therapeutic option forCOVID-19. There are thousands of people who have recovered from COVID-19 in the New York City area whohave donated their plasma to help others who are suffering from this disease. This project is a collaborativerandomized blinded placebo-controlled trial to evaluate the efficacy of treatment with CP in hospitalized patientswith COVID-19 that is being conducted at three New York University (NYU) Langone Health hospitals inManhattan, Brooklyn and Long Island, Bellevue Hospital Center, and three Montefiore Medical Center (MMC)hospitals in the Bronx. We designed and launched this trial as the pandemic surged in NYC by rapidly developinga multicenter, well-powered Phase 2 trial via regional collaborations established by Einstein-Montefiore andNYU-Langone CTSAs with support from the New York Blood Center (NYBC). The hypothesis underpinning thetrial is that compared to placebo, administration of CP will avert respiratory deterioration, the main cause of deathin patients with COVID-19. The specific aims of this project are: 1) To examine whether CP decreases thelikelihood of respiratory deterioration in patients hospitalized for COVID-19 compared to placebo (saline solution,SS) at 14 days from administration, and 2) To identify associations between quantitative and qualitative SARS-CoV-2 antibody levels and clinical outcomes in patients hospitalized for COVID-19 who receive CP and placebo.The public health benefit of proof of CP efficacy against COVID-19, which has already caused 338,000 infectionsand 21,845 deaths in the United States and 187,250 infections and 1,127 deaths in New York City would be atremendous and public health advance that could save thousands of lives.",,2021,Albert Einstein College Of Medicine,4325153,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,,Innovation,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Phase 0 clinical trial",2020 +P21160,P00245,Epidemiological modelling to support the global COVID-19 response: how to mitigate impact in low-income and crisis-affected settings,"The current COVID-19 pandemic is the greatest threat posed by a respiratory virus since the 1918 H1N1 influenza pandemic. To date, the majority of epidemiological modelling analyses have focused on high-income countries. However, there is an equivalent need for models appropriate to low- and middle-income countries (LMICs) that comprise 85% of the world’s population and have differing demographics and behaviours that are not captured by existing models. To address this, we will use a model of SARS-CoV-2 transmission to forecast epidemics and healthcare needs in LMICs, explore the potential impact of proposed interventions, and estimate their impact in real-time. The model will fit to individual country surveillance data to support estimation of the reproduction number, and projections will be made of the potential impact of alternative mitigation and suppression strategies, including household quarantine and social distancing, both generally and in vulnerable populations. The fit of the model to COVID-19 case count and mortality data collected after the implementation of various interventions will be used in real-time to evaluate their effectiveness in individual LMIC countries and the criteria for lifting social distancing measures explored using the best fit model.",,2020,Unknown,119863.36,Other,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,France,Europe,,,Data Management and Data Sharing,,,,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P21161,MR/T043482/1,Virus Wars: Are E3-Targeted Therapies A New Hope?,,,2025,University of Glasgow,1679014.46,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Therapeutics research, development and implementation",,2021 +P21162,174914,"The Canadian Severe Acute Respiratory Infection, Prospective, Perpetual Observational Study: Informing Clinical Care and the Public Health Response","Severe acute respiratory infection (SARI) is a major public health problem. The commonest cause of SARI is influenza which is responsible for substantial illness and death each year, in addition to outbreaks and periodic pandemics. Recent outbreaks of pandemic influenza viruses and coronaviruses such as COVID-19, have taught us not only that these viruses can lead to severe illness and death, but also that it can take a long time between the start of an outbreak and when the health care system knows enough about the illness to guide public health policy and clinical care. Each year since 2016, with a network of hospitals and infectious diseases and critical care clinicians, we have described severe respiratory infection in Canadian hospitals, the viruses and bacteria that cause people to get sick, their treatments and how often it leads to patients needing critical care or dying. When the COVID-19 pandemic hit, this team of over 50 adult and children's hospitals worked in collaboration with the World Health Organization and partners in other countries to describe severe illness from this new virus. We found that patients were typically older, more commonly men and often had pre-existing medical problems. Of patients who were sick enough to need admission to the intensive care unit, about one-quarter unfortunately still died; however, this is a much lower death rate than in many other countries hit hard by the pandemic. This ongoing study will describe whether patterns of illness change in the second and subsequent pandemic waves, and will provide a way to rapidly study common and new respiratory infections in the future to inform policy and practice.",,2023,Sunnybrook Research Institute,359588.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month) | Older adults (65 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,,,Data Management and Data Sharing,,,,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2021 +P21163,174894,"CO-Away: Implementation and Evaluation of Digital Health Solutions for Indigenous Self-Determination, Governance, and Data Sovereignty","During wave 1 of the COVID-19 pandemic, northern Indigenous communities in Saskatchewan experienced a rapid surge of COVID-19 cases, with the highest number of active cases in the province at a time when the rest of Saskatchewan was showing signs of recovery. This is an indication that the timeline of outbreak waves in remote Indigenous communities differs from larger population centres. More distressingly, while the rate of infections in remote Indigenous communities was projected to rise sharply, other parts of the country were already planning to reduce restrictions - reiterating the history of disjointed and bifurcated policy towards Indigenous Peoples. The 1918 influenza pandemic swept across the frozen lakes and boreal forests to devastate communities in the north. 100 years later, the risk to remote Indigenous communities is still high, especially because inadequate housing and overcrowding increase COVID-19 transmission. To address this risk, we have developed CO-Away, a culturally-responsive digital epidemiological platform to monitor, mitigate, and manage Coronavirus disease (COVID-19) outbreaks. CO-Away's purpose is to serve Indigenous communities and enable Indigenous self-governance, determination, and data sovereignty. CO-Away will be launched in Ile-a-la-Crosse, a subarctic northern community in Saskatchewan. The CO-Away platform consists of two key components - a frontend virtual care smartphone application (app), and a backend digital decision-making dashboard. The app provides three key precision medicine services that are specific to each citizen: 1) continuous risk assessment of contracting COVID-19 via the virtual doctor feature; 2) evidence-based public health communication; and 3) Citizen reporting of food availability, access to public services, and COVID-19 symptoms and test results - these culturally-responsive features have been co-created with Ile-a-la-Crosse Metis decision-makers based on imminent community needs and preferences.",,2023,University of Regina,438002.86,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,,Data Management and Data Sharing | Digital Health | Innovation,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Approaches to public health interventions | Community engagement | Communication,2021 +P21166,NIHR202310,Evaluation of the implementation of pandemic preparedness plans during COVID-19 at the interface with infection prevention and control services in acute and community care.,"Background: During the UK COVID-19 epidemic Infection Prevention & Control (IPC) services faced unique challenges in preventing transmission of infection in health and social care settings. It is unclear how healthcare pandemic preparedness plans informed the response to COVID-19 and the extent to which they were effective. Evaluation of the pandemic response is essential in order to learn critical lessons for IPC services and build more effective and resilient IPC plans for future pandemics Research question: How did IPC services in local healthcare systems in England function in relation to pandemic preparedness, and innovate to provide an expert service for preventing transmission of COVID-19 to patients, healthcare workers and the public during the pandemic? Aims: to understand and learn critical lessons from challenges faced by IPC services managing the COVID-19 pandemic across local healthcare systems in England and inform the effective and resilient pandemic preparedness plans for recovery and the future. Objectives: Conduct a secondary analysis of key documents to inform the development of a pandemic policy timeline and identify how IPC services featured in the decision-making processes. Identify how local pandemic plans impacted on the operationalisation of IPC services response to COVID-19. Identify how national guidance and policy decisions impacted on IPC services workload, advice, activity and success in preventing the transmission of COVID-9. Explore how local pandemic plan worked/ did not work in the context of IPC services and how IPC services innovated technically and system wide in response to national and local circumstances. Map how IPC service decisions were made, managed, operationalised and communicated nationally and within local healthcare system. Assess the impact of IPC services decisions on the experience of patients and relatives. Methods: A two-phase, explanatory mixed methods design will be used to evaluate the local context of IPC services in implementing pandemic preparedness plans and the impact of national guidance and policy decisions. Phase 1 will comprise an analysis of UK policy documentation and review of pandemic planning literature, together with a survey of IPC leaders to investigate how local pandemic plans informed the IPC service response to COVID-19. Phase 2 will use 6-8 case studies of local healthcare systems to determine how the IPC service adapted and managed the complexity of the COVID-19 pandemic and why IPC services need to be re-designed to meet the IPC challenges of novel pandemic infections. Findings will be triangulated to produce a pandemic preparedness framework for IPC services and set of indicators to assess local healthcare system preparedness and response to novel pandemic threats. Timeline: 18 months Anticipated impact: Enhanced clarity about the role, requirements and activities of IPC services in pandemic preparedness to underpin NHS England policies and guidance and DHSC oversight of emergency preparedness. Improved understanding how to operationalise the IPC service in pandemic planning for future outbreaks, improving patient safety and patient experience. Dissemination: policy makers, practitioners, patients and the wider NHS system through a stakeholder event, publication and other formats such as blogs, infographics and social media.",,2023,The University of West London,535686.54,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Data Management and Data Sharing,,,United Kingdom,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | IPC in health care settings | Approaches to public health interventions | Policy research and interventions,2021 +P21168,MC_PC_21023,The Influenza Virus Toolkit: a reagent sharing resource for influenza research,"The aim of this proposal is to develop an influenza virus reagent resource, an outward-facing national asset for the long-term storage and redistribution of influenza virology reagents. Influenza viruses are one of the leading global causes of respiratory illness and have been the subject of intensive research over decades. This has created a highly active but dispersed research environment. A wealth of non-commercial reagents exists, but they are challenging to identify and time-consuming to obtain, and requests for them create significant administrative and archiving burdens for the originating groups. We will address this by creating the Influenza Virus Toolkit, a resource-sharing initiative modelled after our recently developed Coronavirus Toolkit. This will build on the established MRC Reagents and Services framework and the CVR Reagent Repository to provide a sustainable, long-term framework for the archiving and redistribution of reagents for influenza virus research, for academics and industry, in the UK and overseas. This project will mobilise resources in the extremely active field of influenza virology, in particular catalysing resource sharing from the current MRC portfolio of virology research. It will foster open-science and a culture of collaboration among influenza researchers. Importantly, it will also create a key resource for the rapid provision of research reagents during the next influenza pandemic.",,2023,University of Glasgow,269950.05,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Data Management and Data Sharing,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21170,1R01AI161152-01A1,Serologic and Molecular Studies of human anti-hCoV antibody cross-immunity and protective responses among endemic HCoVs and SARS-CoV2,"Project Summary The emergence of the novel human betacoronavirus SARS-CoV2 in Wuhan, China in 2019 has rapidly evolved into a worldwide pandemic. Over a 100 million people have been infected and there have been several million deaths. There is also great disparity in the manner in which COVID-19 illness presents, from asymptomatic infection to death. COVID-19 illness in children is overall more mild or asymptomatic compared to adults. One hypothesis that may explain this disparity is that children have cross-immunity to SARS-CoV2 due to frequent early exposure to globally circulating human coronaviruses (HCoVs) that cause a milder respiratory illness. Whether there is some level of cross-immunity between the endemic HCoVs and SARS-CoV2 that carries into adulthood and can provide some level of protection from COVID-19 disease is the subject of this R01 application. Our primary goal is to provide serologic and molecular evidence of anti-HCoV/SARS-CoV2 spike (S) cross- reactive and neutralizing antibodies that can provide protection against SARS-CoV2 in vivo. We have an IRB- approved protocol to collect blood samples on 250 COVID-19 individuals. Our COVID cohort is comprised of 5 groups that includes adult and pediatric cancer patients, adult and pediatric healthcare providers and adults without COVID patient contact. In addition, we will study our pre-pandemic seasonal influenza cohort for evidence of pre-existing anti-SARS-CoV2 S Abs. In Aim 1 we will quantify the present of anti-S HCoV antibodies and quantitate their cross-reactivity to SARS-CoV2 S. The studies in subaim 1A will include FACS staining of S expressing cells and ELISAs of S subdomains for epitope mapping. In subaim 1B, selected plasma samples within each study group will be used for affinity column purification of plasma IgGs that will be passaged over and eluted from one of 4 HCoV or SARS-CoV2 spike columns and tested for cross-binding, cross-Fc effector activity and cross-neutralization activity. In subaim 1C, these purified IgGs will be tested in vivo in hACE2 mice for cross-protection against SARS-CoV2 challenge. In Aim 2 we will establish the molecular basis by which bi- directional immunity to among CoVs could provide cross immunity to HCoVs and SARS-CoV2 through common spike epitope recognition. In subaim 2A, we will perform memory B (mB) cell screening for presence of S cross- binding. Single mB cells that bind at least one hCoV S protein and SARS-CoV2 S will be isolated by FACS, their cognate VH/VL genes cloned, expressed as whole IgG1 mAbs and tested for cross-binding, virus neutralization and Fc effector activity against the different HoCoVs, SARS and SARS-CoV2. In subaim 2B, mAbs with cross- CoV activity will be tested in mouse and hamster models for protection against SARS-CoV2 challenge. In subaim 2C, we will adapt the novel LibraSeq technique to capture the single or multi-spike binding specificity, BCR repertoires and transcriptomes of selected Bm cells to study the potential different evolutionary origins that may exist between mono-spike and multi-spike binding cells. This R01 grant will provide proof-of-principle molecular studies of HCoV/SARS-CoV2 Ab cross-immunity that may aid in COVID-19 vaccine design.",,2024,Unknown,903360,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Individuals with multimorbidity,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease models | Disease surveillance & mapping,2021 +P21171,1R44OD031437-01,Wirelessly controlled BSL3 vivarium system for automated microdosing in studies of infectious diseases,"Project Summary Infectious diseases are caused by micro-organisms, such as bacteria, protozoa, viruses or fungi, which can be transferred through direct or indirect human contact. A viral infection occurs when a host's body is invaded by pathogenic viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 and the current pandemic. This pandemic is the greatest public health challenge since the 1918 influenza pandemic and the biggest threat to destabilizing the global economy since World War II. As viruses tend to mutate quicker than other pathogenic agents (and thus newer strains emerge time and again), continuous research is required to combat infectious agents. For preclinical research, the most frequently used animal models are mice and rats. They offer an optimal combination of genetic proximity to humans, cost for breeding and colony maintenance possibilities due to their small size. Mice offer the broadest spectrum of available models. Rats are the second most frequently used mammal animal model. In fact, several SARS-CoV- 2 researchers are turning to rats. They are no more susceptible to COVID-19 than mice, but their larger size is an advantage, as, for example, researchers often want to do repetitive bleeding in an experiment but cannot do that with mice. Furthermore, as vaccine studies often assess how different doses affect antibody responses over several days, most toxicology studies of drugs also start in rat. To achieve intermittent infusions in most non-infectious disease research, the current prevailing administration modes for small animal research are manual (oral, intravenous, intraperitoneal, subcutaneous) requiring repeated handling by trained technicians. However, infectious disease researchers desire the least number of touchpoints possible with their infected animals, especially when sharp needles are involved The proposed FluidSync BSL3 system may aid the discovery of new treatments for COVID-19 by enabling candidate drugs to be administered to model animals infected with SARS-CoV-2 while minimizing investigator contact. It may also be used in the development of vaccines and antibodies. The system builds on the first and only wireless and tether-free administration system that can be used in animals as small as mice. The new system will have new capabilities including i) a medical-grade primary battery and ii) a programmable system-on-chip including Bluetooth telemetry transceiver, processor and memory. Ultimately, the FluidSync BSL3 microinfusion system would enable an intelligent instrumented vivarium system that addresses many BSL3 user requirements with benefits including increased productivity, reduced researcher exposure to potentially toxic drugs and disease vectors, ease of management of large-scale animal studies, and minimized animal handling to reduce white coat effects.",,2023,Unknown,1273102,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies,2021 +P21172,NIHR150879,Physical interventions to interrupt or reduce the spread of respiratory viruses,,,2022,Cochrane Acute Respiratory Infections Group,13500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +P21175,2104830,Investigating the Long-Term Impacts of Pandemic Disease,"This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from under-represented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Under the sponsorship of Dr. Sharon DeWitte at the University of South Carolina, this postdoctoral fellowship award supports an early career scientist investigating the long-term impacts of pandemics on population health and demography by studying how the 1918 “Spanish” influenza pandemic influenced the health of influenza survivors and how sex and race mediated these changes. The results of this project will be used to support public health measures that will mitigate the negative impacts of Covid-19. Novel data on gendered and racial health disparities will be generated, increasing knowledge of health inequality in the past, and contributing to current discourse on health disparity and the social determinants of health. Characterizing how pandemic influenza influences mortality among various populations will help inform predictions of how future outbreaks will affect modern society. Results on how demography influenced long-term survival in 1918 will be used to understand how sex and race may affect health and mortality of Covid-19 survivors.

This project has the following research goals: understand how overall population health changed after the pandemic and characterize how sex and social race influenced health and survival. Previous studies on the 1918 flu pandemic have relied primarily on documentary evidence â€"" such as hospital or death records â€"" or on viral RNA extracted from a handful of individuals. Researchers have been unable to explore factors influencing mortality on a population scale from a biological perspective. This project will use an untapped source of data: human skeletal remains of individuals who survived the 1918 pandemic. This proposed project takes a bioarchaeological approach, analyzing the skeletal remains of individuals who died before and after the 1918 pandemic. Skeletal lesions associated with increased morbidity and mortality will be analyzed alongside ages-at-death using hazards analysis to assess if post-pandemic populations lived longer or had less disease compared pre-pandemic populations. Differences in survivorship and lesion prevalence will also be assessed by sex and social race to examine if demographic factors influenced mortality and survival. The findings of this research on how sex and social race influenced long term survival in 1918 can predict how demography will influence health and mortality in Covid-19 survivors in the upcoming years. The information learned from this project will be disseminated through lectures increasing public literacy of the roles sex and social race play in creating health disparity, educating the public about virus transmission, and increasing public awareness of the ongoing danger of epidemics in our highly interconnected society.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2023,"Wissler, Amanda",138000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,,,Data Management and Data Sharing | Gender,,,,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2021 +P21176,1R21NS122280-01A1,Synergistic Interactions of SARs-CoV2 and environmental toxicants in Experimental Parkinsonism,"ABSTRACT Approximately16.5 million people have been infected with the SARS-CoV2 virus with approximately 650,000 (and rising) deaths. While primarily a respiratory virus, clinical observations appear to demonstrate nervous system involvement. These include those associated with the CNS (headache, confusion, seizure, stoke), PNS (pain, anosmia, ageusia) and enteric nervous systems (ENS, diarrhea). What is not fully understood- at this time- is how the SARS-CoV2 virus produces these nervous system disorders. We also do not know if the impact(s) on the nervous system will persist, or possibly even become apparent, post infection. Previous studies in my lab examining neurotropic (H5N1 influenza, western equine encephalitic virus) and non-neurotropic (pandemic H1N1 influenza) have shown that each can produce immediate and/or delayed effects in the CNS, including induction of pathologies seen in Parkinson’s disease. Related to SARs-CoV2, a number of recent studies, using autopsy material has examined the localization of SARS-CoV-2 virus in the brain. From these studies, approximately 36% had apparently low levels of viral SARS-CoV-2 RNA and protein in brain, although in each of these studies a complete cellular and localization map have not been reported. Also, it is not known if the viral particles found in the CNS were present intracellularly due to inherent neurotropism or were only present in the CNS due to breaches in the cerebral vasculature. (i.e., secondary to cerebrovascular damage). Even without neurotropism, an understanding of changes in the nervous system are critical since it is that any immediate and/or delayed effects may result from dysfunctional signals (peripheral cytokine storms) that arise outside of the nervous system; yet impact the function and, perhaps, survival of neurons. To address these unanswered questions, two specific aims are proposed. In Specific Aim 1, we will empirically determine the neurotropic potential of the SARS-CoV2 virus (USA-WA1) throughout its natural period of infection in the CNS, PNS and ENS in C57BL/6J mice and C57BL/6J mice expressing a human ACE2 receptor (K18-hACE2, B6.Cg-Tg(K18-ACE2)2Prlmn/J). We will also examine the induced inflammatory response in the periphery and brain. In Specific Aim 2, we will determine if resolved SARS- CoV2 infection can sensitize SNpc DA neurons to agents that have been shown to induce parkinsonism (paraquat and rotenone) in mice and humans as well as if it can exacerbate the spread and extent of alpha-synuclein pathology. These aims and associated experiments will allow us to directly determine the neurotropic and immunogenic potential of SARS-CoV2. They will also allow us to determine this virus has the potential to sensitize neurons to exogenous insults as has been demonstrated with some other respiratory viruses. Understanding if this pandemic virus affects the CNS and in particular, the basal ganglia is important for both short term treatment as well as longer-term management of post infection effects. Additionally, understanding the neuropathological sequalae of SARS-CoV2 on the nervous system will be necessary for later studies examining if a therapeutic intervention (i.e. vaccine or modulator of inflammatory response) can protect against primary and/or secondary nervous system effects of this respiratory infection.",,2022,Unknown,429000,Animals | Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity | Disease models | Disease pathogenesis",2021 +P21177,1R21EB031347-01,A muco-penetrating biomaterial-based subunit vaccine for programming protective immune responses to SARS-CoV-2,"1. ABSTRACT/SUMMARY Given that the site of entry of SARS-CoV-2 is the respiratory mucosa, an effective vaccine for SARS-CoV-2 should initiate both humoral and respiratory mucosal immune responses. Although an intranasal subunit vaccine would be an ideal platform for SARS-CoV-2, transport across the nasal mucosa and a lack of safe and effective mucosal vaccine adjuvants thwart the development of a clinically-viable intranasal subunit vaccine. We propose to develop an intranasal vaccine composed of SARS-CoV-2 proteins conjugated to an immunostimulatory biomaterial that overcomes the transport barriers of the nasal mucosa and thus induces protective mucosal and systemic immunity. Our platform is composed of SARS-CoV-2 receptor-binding domain portion (RBD) conjugated to water-soluble polymers, termed MPGAP, that are synthesized from monomers that bind nasal mucus, disrupt endothelial thigh junctions, and target and activate antigen presenting cells (APCs). Thus, when administered intranasally, RBD- MPGAP conjugates should (1) adhere to nasal mucus, increasing residency time at the nasal epithelium, (2) dismantle tight junctions, maximizing paracellular transport to underlying APCs and nasal associated lymphoid tissue, (3) target conjugated RBD to and activate APCs, eliciting APC-derived signals that activate T and B cells. By overcoming the biological barriers of the nasal endothelium and targeting immunostimulatory factors to immune cells, RBD- MPGAP should induce protective mucosal and systemic immunity in the absence of off-target effects. RBD-MPGAP conjugates will be produced, characterized, and their ability to bind nasal mucus, enhance paracellular transport, and target and activate antigen presenting cells will be tested in mice. The neutralizing antibody titer of serum and respiratory fluids from RBD-MPGAP-immunized mice will be assessed via an in-vitro SARS-CoV-2 neutralization assay. Finally, the protective efficacy and durability of the mucosal and systemic immunity elicited by internasal RBD-MPGAP will be investigated in a SARS-CoV-2 mouse model. Completion of this project will validate the preclinical efficacy of an intranasal SARS-CoV-2 subunit vaccine and deliver a platform that could combat numerous other respiratory infections, from seasonal influenza to the next respiratory viral pandemic.",,2024,Unknown,204688,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P21178,224690,"Ready2Respond, a public-private collaborating platform to address pandemic preparedness gaps in low- and middle-income countries - Phase 2 Funding","Following a 2019 meeting of global health leaders with expertise in influenza, vaccinology and pandemic preparedness in London hosted at the Wellcome Trust, Ready2Respond was formed as a global collaboration of partners committed to enhancing low- and middle-income countries' readiness to respond against influenza and respiratory pandemics. With a Secretariat hosted at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza, the organization's plan now includes COVID-19. Under the oversight of a Management Secretariat, Expert Working Groups design and execute cross-collaborative projects organized in 3 strategic pillars: - Burden of Disease - Risk Communication and Community Engagement - Vaccine Access Ready2Respond seeks a grant from the Wellcome Trust of US$ 492,970. This grant will enable Ready2Respond to focus on two initial and critical projects identified in the Burden of Disease pillar. This grant will also allow for retention of paid Director, responsible for ensuring that identified projects represent discrete operational improvement activities for LMICs, and cover part-time staff. Finally, this grant will help secure communication activities aimed at raising awareness and funding from potential partners. This Phase 2 of funding will span September 2021 - February 2022.",,2022,Task Force for Global Health,505984.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Communication,2021 +P21192,220776,Mechanism of cell-to-cell transmission of flaviviruses,"This proposal will investigate the mechanism of cell-to-cell transmission and spread of flaviviruses using Dengue and Zika as model systems. We will therefore address a longstanding debate on how they exit from infected cells, and preferentially spread into specific cell types. Dengue and Zika are the two most prevalent flaviviruses worldwide, sharing significant overlap in their genome architecture and biology. Dengue infects >50 million people annually, causing severe pathologies. Zika too has emerged as a global threat with recent outbreaks linked to serious neuro-developmental complications in children and Guillain Barré syndrome in adults. No vaccines or therapeutics exist for these viruses, and our current understanding on mechanisms of their transmission and spread is severely limited. Viral infections spread by overcoming multiple barriers to move from cell to cell. Viral progenies can move across extracellular space either as free particles via fluid phase diffusion, within vesicles, or by cell-cell contacts. To understand transmission, we will therefore address: (i) characteristics of the extracellular virus populations, (ii) whether multiple transmission routes exist (iii) whether the viral envelope is the primary determinant of transmissibility. This proposal builds on our previously published and ongoing studies on viral manipulation of autophagy for assembly and spread.",,2025,University of Oxford,2131862.56,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21208,223226,RNA-communication between arboviruses and their hosts,"Flaviviruses such as Zika virus, dengue virus and yellow fever virus transmit their RNA genomes between arthropods and humans, causing widespread pathology and death. During infection, the viral RNA genome resides inside the host cells’ cytoplasm. However, whether the viral genome folds differently inside human and arthropod cells, and whether it interacts with the hosts’ own RNA remain largely unexplored. The aim of this proposal is to dissect the dynamics and function of the flaviviral RNA interactome. I will employ my recent developed COMRADES method to investigate the base pairing capacity and function of two related flaviviruses: Zika virus and yellow fever virus, and to address the following little-explored aspects in their biology: (i) Do viral genomes base-pair with host RNAs? What are the roles of host-virus RNA base-pairing? (ii) Do viral genomes base-pair differently inside different hosts? What are the functional implications? The results will cast light on how RNA viruses utilise RNA base-pairing to enhance their replication and pathogenicity; offer new opportunities to develop antiviral therapeutics targeting the host-virus RNA-RNA interactome; and establish a new role for RNA base-paring in zoonosis.",,2026,University of Cambridge,1843308.19,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P21209,223011,Microenvironment Regulation of Zika Virus Susceptibility in Human Brain Development and Malignant Glioma,"Neural stem cells (NSCs) in the developing embryo brain share transcription programs with glioma stem cells (GSCs) in malignant brain tumours, and both are susceptible to Zika Virus infection. In the developing brain this can result in microcephaly, whereas in brain tumours it could offer insights relevant to oncolytic virus development. However GSC and NSC susceptibility to Zika and other viruses depends on the microenvironment. In particular, microglia progenitors migrating into the embryo brain from the yolk sac are believed to bring virus with them, whereas my preliminary data suggests that mature tumour-associated microglia instead drive a virus resistance phenotype in GSCs. This project seeks to establish the mechanistic basis for the microenvironment regulation of virus susceptibility in normal and malignant progenitors, and to suggest therapeutic strategies for modulation of these.",,2026,Cambridge University Hospitals NHS Foundation Trust,1086069.6,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2022 +P21211,TMA2019PF-2694,Use of an Aedes Salivary Biomarker to Assess Arboviral disease Transmission Risk in Northern Tanzania (SABIOT),"Aedes mosquitoes are the most threatening disease vectors worldwide. Among the most important arbovirus such as dengue, Zika, Yellow fever and Chikungunya can cause a serious broad spectrum of manifestation such as hemorrhagic fever, Shock syndrome, chronic joint pain, microcephaly and multi-system failure. In absence of effective treatment and vaccine, vector control remains to be effective measure to prevent the transmission of mosquito-borne diseases which can be achieved through management of breeding sites, indoor residual spraying and to conduct extensive surveillance of these mosquito populations to estimate risk of transmission. However, these methods are time consuming, expensive and labor intensive, hence it is difficult to apply on large scales. To increase the efficacy of vector control programs, a new epidemiological methodology has been documented. This methodology can reliably measure arboviral transmission dynamics that will enable more accurate and useful predictions of outbreaks. This method can be used to identify areas of risk for Aedes-borne diseases and evaluate vector control interventions. A cross sectional study is designed to assess the usefulness of the salivary biomarker for measuring human exposure to Aedes bites and evaluate the efficacy of Aedes control strategies in Northern Tanzania. Participants will be recruited during the end of rainy season. Participants will be followed longitudinally to screen for Aedes mosquito exposure by quantifying IgG antibody response against Aedes salivary gland peptides. These data will uncover the risk of arboviral transmission in Tanzania. Data generated will provide an early warning of increased risk of transmission of arboviral disease and early warning signs of outbreaks. More importantly, assist health authorities and policy-makers to better plan for and timely interventions. Hypothesis: The level of IgG Ab response to Aedes salivary proteins is associated to human exposure to vector bites and is consequently related to the risk of dengue, zika and chikungunya transmission in Northern Tanzania.",,2023,Kilimanjaro Clinical Research Institute (KCRI)/ Kilimanjaro Christian Medical Centre (KCMC),82930.01,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,European Commission,Europe,Europe,Africa,,,,,Tanzania,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Vector biology | Disease transmission dynamics,2021 +P21212,3U01AI151807-02S1,Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO),"ABSTRACT The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO) network provides a nimble and flexible network of surveillance sites in Central and South America coupled to cutting-edge modeling approaches to anticipate and counter emerging zoonoses and arboviruses. CREATE- NEO forewarns local, regional, and global public health agencies of zoonoses and arboviruses that pose particularly high risk of spillover, emergence into transmission among humans, and/or international spread. The parent grant 1U01 AI151807 supports CREATE-NEO operations during typical conditions of emerging zoonoses and arbovirus activity. Since, 2020 we have built local capacity to detect, predict and respond to such emergence events at their point of origin, thereby maximizing the potential to avert full-blown emergence. Critical activities included: (i) genomic surveillance with deep sequencing and comprehensive phylogenetic analyses of dengue virus in Sao Jose do Rio Preto (SJdRP), Brazil; (ii) vector and non-human primate surveillance in Brazil and Panama; and (iii) characterization of human cases of Zika, dengue and Ilheus virus infections associated with cerebrovascular and encephalitic events. With the onset of the COVID-19 pandemic, we expanded our activities to include: (iv) characterization of human cases of SARS-CoV-2 and dengue virus coinfection; (v) surveillance of NHPs for potential spillback of SARS-CoV-2; (vi) supporting genomic surveillance of SARS-CoV-2 variants in SJdRP and Panama; and (vii) supporting clinical surveillance of arbovirus circulation in Panama and Brazil. Thus, the emergence and rapid spread of SARs-CoV-2 offers an example of our capacity to quickly redirect resources to address any emerging zoonotic or vector-borne diseases. This U01 supplement will continue and expand these emergency activities in support of NIH-funded and other international research on SARS-CoV-2 through the following supplemental activities related to the parent grant’s original aims. We will expand our genomic surveillance capabilities of SARS-CoV-2 variants in SJdRP and Panama. We will characterize both between-host and within-host diversity through deep sequencing using Illumina technologies and perform comprehensive phylogenetic studies using complete genomic sequences of SARS-COV-2 to infer patterns of virus spread and to inform hypotheses regarding variation in transmissibility and clinical outcomes (Aim 2e).",,2022,Unknown,323943,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Unspecified,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping",2021 +P21221,224459,Transitioning the WMP Wolbachia method for arbovirus control to sustainable scale,"Approximately 40% of the global human population is at risk of acquiring a virus transmitted by the bite of an Aedes aegypti mosquito this year. These viruses cause diseases known as dengue, Zika, chikungunya and yellow fever. Infection can result in death, but in less extreme manifestations it can result in horrific birth abnormalities in babies, extended periods of illness and hospitalisation, loss of income through an inability to work, and disruption of the health system through inundation with people seeking urgent care during outbreaks. Sadly, there are no effective and safe drugs or vaccines available, nor effective methods for controlling the mosquito. As a result the disease burden is climbing year on year. We have found that introducing a natural insect bacterium (Wolbachia) into wild mosquito populations can eliminate the ability of mosquitoes to transmit all of these viruses between people. We have shown this method to be highly efficacious and has the potential to lead to disease elimination. Our goal now is to optimise the remaining technical areas that constrain scaling and to help to build the capacity and undertake the knowledge transfer that will make the intervention available to the billions of people that need it.",,2026,Monash University,19797337.26,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Americas,,,,,Australia,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P21228,2027397,RAPID: Responding to a Global Pandemic--The Role of K-12 Science Teachers,"Education and Human Resources - When a global health crisis emerges, students at all levels turn to their science teachers for information and, at times, reassurance, according to researchers at Horizon Research, Inc. (HRI). Science teachers serve a critically important public health function and become an important part of the nation?s response efforts. Given the magnitude of the current COVID-19 crisis, it is likely that students are bringing their questions and concerns to their science teachers. As this award is made, nearly all K?12 school buildings in the U.S. are closed, and science teachers face unprecedented challenges in carrying out the instruction for which they are responsible while simultaneously addressing students? questions about COVID-19. Moreover, they must do this within new instructional formats. Education is crucial for helping students to understand the facts about the virus, despite much conflicting information and misinformation available. Education helps students understand and actively participate in measures to stop the spread of COVID-19. This award will support a national research study on how teachers are helping students respond to COVID-19. The findings will inform the development of curriculum materials for teaching about COVID-19, which are much needed right now, and help science teachers to adapt their instruction as they help to fulfill a critical public health function. This study will enable a better understanding of the role that science teachers can play in a national response, both now and in future crises.

The research will build on a study of science teachers conducted by HRI following the Ebola outbreak of 2014. Specifically, the research will investigate (1) where teachers of science get their information about coronavirus and COVID-19; (2) what types of resources teachers find most useful; (3) what factors influence whether science teachers address COVID-19 in their instruction; and (4) how science teachers adapt their teaching in response to COVID-19. HRI will recruit a nationally representative sample of several thousand K?12 teachers of science and invite them to complete a survey about their instruction related to COVID-19, both before school buildings closed and after. Using the Theory of Planned Behavior, the survey will be constructed to identify factors that predict whether teachers take up the topic. The survey will also collect data about how teachers address the virus and its transmission with their students. HRI will disaggregate survey data by school-, class-, student-, and teacher-level variables to identify patterns in student opportunities. Survey data will be supplemented by interviews with 50 survey respondents to gather more in-depth information related to the constructs of interest. Study findings will be immediately shared through a preliminary report that focuses on the survey data; mainstream print media using press releases; and social media partnering with the National Science Teaching Association. HRI also will publish policy briefs intended as guidance for schools, districts, and states; and research articles.

This RAPID award is made by the DRK-12 program in the Division of Research on Learning, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act. The Discovery Research PreK-12 program (DRK-12) seeks to significantly enhance the learning and teaching of science, technology, engineering and mathematics by preK-12 students and teachers, through the research and development of new innovations and approaches. Projects in the DRK-12 program build on fundamental research in STEM education and prior research and development efforts that provide theoretical and empirical justification for the projects.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2021,Horizon Research Inc,171208,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,Swiss National Science Foundation (SNSF),Switzerland,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Social impacts,2020 +P21237,P02870,"US-UK Collaboration: Integrating ecology, epidemiology, and human interests to guide strategic management of zoonoses in complex wildlife reservoirs","Wild animals host a wide variety of pathogens that can spread to other animals and humans. Such
diseases, including Ebola and COVID-19, significantly affect human health, agriculture and wildlife
conservation. Historically, disease control methods (e.g. vaccination, therapeutics) have focused on
humans or livestock rather than wild animal reservoirs. Focusing on disease control in wildlife could
be more effective in preventing disease emergence in humans, but that approach is currently limited
by three factors. First, many diseases are maintained in cycles that spread across landscapes, but
wildlife diseases are notoriously difficult to assess at these large spatial scales, making responses to
interventions unpredictable. Second, tools like vaccines have been difficult to administer to sufficient
numbers of animals to actually reduce disease transmission in the wild. Third, interventions are
usually bounded by societal constraints, both financial (e.g., limited funds to invest) and sociological
(e.g., conflicting stakeholder interests). New technologies, including vaccines that can spread among
wildlife and miniaturized animal-borne tracking systems, have unrealized potential to overcome these
limitations. This project will focus on reducing vampire bat transmitted rabies, which has significant
human health and agricultural impacts across Latin America, but the methods developed for this study
could be applied to other important wildlife diseases. The project will strengthen research
capacity through training of students and early career scientists in field, laboratory and quantitative methodologies.

This project will conduct field and laboratory research to test specific hypotheses about the
epidemiology and management of vampire bat-transmitted rabies. The researchers will: (1) Use field
experiments with animal-borne GPS tags and large-scale data on bat presence from questionnaires
and historical rabies outbreaks to generate models that can be used to determine how human
disturbance influences bat abundance and dispersal; (2) Conduct studies using captive and wild
vampire bats to determine host and ecological factors that will influence the use of self-spreading
rabies vaccines that target bats; and (3) Use parameters estimated from fieldwork and captive studies
to optimize strategies for localized control and regional elimination of vampire bat rabies that preserve
diverse stakeholder requirements, e.g. wildlife conservation goals as well as improved human and
livestock health.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2024,University of Wisconsin-Madison,1412944,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Eastern Mediterranean,,Innovation,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector control strategies,2020 +P21245,P04191,DIFFERENTIATION AND FUNCTION OF MONOCYTES AND MACROPHAGES,"Project Summary Although much remains unclear with respect to the pathogenesis of COVID-19, the possibilities that cytokine storm and altered coagulation contribute to adverse disease pathogenesis have emerged. Both the cytokine output and promotion of coagulation may be mediated by activated monocytes. Monocytes, for instance, are the central leukocyte in blood to express tissue factor (F3) and initiate coagulation and this activity promotes comorbidity in Ebola and HIV infections. One cytokine that seems most notably elevated in plasma of COVID patients is IL-6. In keeping with the potential importance of IL-6 in cytokine storm, our preliminary data reveal that blood monocytes, of all subsets, are a major source of IL-6 in COVID leukocytes and that their production of IL-6 positively correlates with adverse disease progression. Surprisingly, though monocytes produce cytokines, other features of canonical activation were not present in monocyte subsets of COVID patients. Particularlyy, induction of functional tissue factor in IL-6-producing monocytes was minimal to absent. This was in striking contrast to control monocytes from healthy subjects treated ex vivo with LPS or resiquimod. Giventhe clinical concern that coagulation may be altered in COVID-19 and contribute to pathogenesis of adversedisease and given the very robust expression of IL-6, we were especially surprised that tissue factor was notinduced. Overall, it appears that the stimulus for activation of monocytes in COVID-19 patients is distinct fromcanonical responses that also induce tissue factor in cytokine-producing cells, or perhaps a subset ofmonocytes able to activate the tissue factor pathway is missing or in extracted COVID-19 PBMCs. Theoverarching aim of this work is to define, using a robust longitudinal dataset, whether proinflammatory activation of monocyte subsets in blood associates with disease severity and to define the core characteristics of such activation. We will also carry out exploratory analyses in search of signals that lead to such activation. A key resource for our proposal is access to a bank of frozen PBMC, serum, plasma and whole blood in which longitudinal blood draws are being collected on 300 COVID-19 patients of differing disease severity admitted to Barnes Jewish Hospital. This bank has been established by the Institutional Clinical and Translational Research program at Washington University School of Medicine. Resources from this bank will be coupled with a stock of frozen PBMCs from >50 control participants in our laboratory and PBMCs from HIV subjects, where the state of monocyte activation will be compared with that of monocytes derived from COVID patients.",,2020,Washington University,164107,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P21248,2000175,Excellence in Research: Biophysical mechanism by which mannose and N glycans modifies and protects biological surfaces,"The surface of pathogens is shielded by short polymers of sugars known as glycans. Glycans mask pathogens and signature molecules from host cells and confound therapeutic treatments. N-glycans are the commonly found type of glycans found on cell surfaces. Pathogens like Ebola, SARS, HIV, and COVID 19 are shielded by N-glycans having high mannose content, with the mannose content sometimes increasing during the host infection. The goal of the proposal is to investigate what biophysical properties of mannose residues present in shields of N-glycans confer protection of pathogens against the host immune system. This project will train graduate and undergraduate students and provide an annual hands-on STEM workshops to engage high school students in research and everyday science. Understanding how mannose residues presented in N-glycans protect pathogens will help us strategically disarm the glycan shield fortress, thereby making pathogens more vulnerable to detection, sanitizing, and treatment.

Despite the ubiquitous presence of glycan sugars on biological surfaces, little is known currently about how glycans steer interfacial effects like aggregation, biofilm formation, charge shielding, antifouling, immune-stealth, and transport through mucus. This project will lead to a better understanding of the biophysics of mannose residues when presented in N-glycan architecture along with non-mannose sugars, and how they relate to the improved solubility and aggregation, mucous penetration, and immune evasion of glycosylated molecules. To understand the uniqueness of mannose biophysics and how it interplays with other N-glycan sugars, the cross- and self- interactions of all N-glycan sugars will be determined, and rules for integrating single-sugar biophysics to glycosylated system behavior will be evaluated. A pseudo-typed HIV virus is the controlled sugar-presentation platform. These studies will synergistically link observations from force-spectroscopy, rheology, and dynamic light scattering, along with perturbations from glycosidase and lectin addition. This project is jointly supported by the Historically Black Colleges and Universities (HBCU) Excellence in Research program and the Molecular Biophysics program in the Molecular and Cellular Biosciences Division.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2023,Howard University,499959,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21252,2011109,"US-UK Collab: Heterogeneities, Diversity and the Evolution of Infectious Disease","The aim of this project is to understand the effect of disease severity on the spread and evolution of infectious diseases, and its significance for infectious disease management and control. Recent and current epidemics emphasize that there is a pressing need to understand what makes some infectious diseases so devastating. Pathogens from the common cold through seasonal flu, SARS-1, SARS-2, and Ebola vary remarkably in how deadly they are and how well they transmit between people. Moreover, there is considerable variation in the impact that a specific disease will have on different individuals in a population. For example, some individuals get sicker than others, and importantly some will act as superspreaders of the pathogen. This type of variation is typical of infectious diseases in humans and other species, including livestock, crops and wildlife. To answer these questions the researchers will combine mathematical and computational models to develop new evolutionary theory that will explain the important factors responsible for variation in the outcome of an infection. The findings from the theory will be tested experimentally using an insect disease system in the laboratories at UC Berkeley. The mathematical modelling and experimental analysis can then be applied to real systems. A particular focus will be to examine the impact of different agricultural management practice on the severity of disease in agricultural systems, for example, which farming practices lead to the evolution of more virulent disease. Understanding what determines the virulence of infectious disease is critical to the effective management of current and emerging disease threats.

Individual hosts vary in their susceptibility and transmissibility through genetic and epigenetic effects, their condition, and their immune memory. Individual hosts also vary in their disease contacts within a population due to how individuals are arranged in space, how they move, and how they interact, all of which can generate population structure even in the absence of heterogeneities in the environment. These individual heterogeneities and the heterogeneity in transmission due to population structure can interact with heterogeneities that arise from specific interactons between host and parasites genotype. This project will test theories about the effects each of these three sources of heterogeneity (individual, population and interaction) have on the epidemiology of disease. How these different heterogeneities interact to determine the evolution of disease virulence and host defense is little studied. New theory is therefore required to test these interactions? implications to both long-term evolutionary outcomes and short-term transient dynamics. This project will: (1) develop theory to predict how these heterogeneities interact to determine long-term outcomes and transient evolutionary behavior, (2) test these predictions in a tractable laboratory model system (larvae of the moth Plodia interpunctella infected with PiGV), and (3) develop models to predict the impact of heterogeneities on the evolution of pathogens in agricultural systems.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.",,2025,University of California-Berkeley,1559024,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease,Swiss National Science Foundation (SNSF),Switzerland,Europe,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease models | Disease transmission dynamics",2020 +P21261,172686,Evaluating the Governance of Emergent Pandemic Zoonoses: A Systems and Legal Analysis of Wildlife Markets,"Although mitigating the current pandemic is critically important, a governance response is needed to prevent future pandemics. We need actionable evidence that focuses on the regulation of wildlife trade from which SARS and SARS-Cov2 are believed to have emerged. Specifically understanding the social, legal and cultural dynamics that affect the regulation of wildlife markets in countries where zoonotic epidemics (Ebola) and pandemics (SARs, and SAR CoV-2) emerged, including China, the Democratic Republic of the Congo and the Philippines. Therefore, the purpose of this project will be to evaluate the governance gap in stewardship of international wildlife trade supply chains given their implications for food and health security by analyzing the intersection of global biodiversity, environmental, agricultural and public health governance systems. Within each participating country an institutional and legal epidemiologic analysis will provide policy surveillance and mapping of international and national policy. A systems analysis will be used to identify local contextual interdependencies among laws, regulations, and their implications for the behaviour of social and political actors and communities supplemented by in-depth qualitative case studies. The empirical evidence from these analyses will be integrated into a report and set of policy recommendations that will be utilized in a process to inform the development of a policy design and implementation toolkit for international organizations, national and local stakeholders who will be engaged throughout the research process.",,2020,York University,326245.76,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Europe,,,,,United Kingdom,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +P21265,NIHR133333,NIHR Global Health Research Group on Building Partnerships for Resilience: strengthening responses to health shocks from the grassroots,AIM: To develop and strengthen an international partnership to conduct research to inform policy and practice that improves effective community-led responses to environment-related public-health crises. BACKGROUND: Human health and wellbeing face threats from increasingly frequent and disruptive shocks including outbreaks (some pandemic) of zoonotic infections (Ebola Covid19) and severe environmental change heightened by climate change that lead to changes in food security disease patterns and disasters. These challenges are interconnected yet policy and governance systems have failed to achieve holistic cross-sector responses. Unpredictability of crises makes it hard to plan for them. Social science work has shown that resilience for responding to shocks is most effectively built at community level. However no robust data exist on the mechanisms by which formal health and other sectors can engage with learn from and support resilience-building at the grassroots to develop effective health responses. Our Group will gather evidence from Ethiopia Madagascar Sierra Leone Uganda which have experienced a range of public health crises. DESIGN AND METHODS: Our multi-disciplinary comparative case-study approach will apply cutting edge combinations of social science methods across five objectives over three years:1) Synthesise evidence on how communities local health systems and other formal and informal entities have responded to health crises and with what effect :Narrative synthesis of literature from databases and websites of Government UN donor and third sector agencies. Synthesis of existing qualitative and epidemiological datasets (COVID-19; Ebola; environmental disasters and stresses) held by partners.2) Design effective approaches for public health crisis-response at grassroots: Identify common principles of effective responses; develop evaluation indicators measuring effectiveness; design prototype response models (i.e. ideal evidence-based approaches that are likely to effectively establish and sustain community-led public health responses).3) Evaluate models for effective community-led responses to public-health crises. Case studies of models identified as effective during evidence synthesis: in-depth interviews and focus groups; ethnographic work in district health offices and village communities. If outbreaks/health crises occur during project implementation we will prospectively implement and evaluate prototype approaches: same methods as for case studies.4) Formulate guidance and create dialogue with stakeholders on how to strengthen local resilience for effective responses to public health crises.5) Strengthen and consolidate sustainable partner research and management capacities to strengthen policy and practice in crisis-response.COMMUNITY ENGAGEMENTCommunity engagement is central to our research questions process and results: e.g. “citizen science” approaches grassroots innovation and identifying common drivers of success. Community members will be involved and trained as volunteers/researchers.DISSEMINATIONMultiple pathways include: National (Ministries of Health Agriculture Environment other sector Ministries; Population-Health-Environment (PHE) networks); Global/Regional (academic networks; emergency response organisations; funding agencies; WHO).,,2025,London School of Hygiene & Tropical Medicine,3504918.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P21266,CSA2019ERC-2683,"Moving Tanzania’s Clinical Research Ethics and Medicines Regulatory Capacity to the next level: Fostering Medicine Quality, Safety and GCP Clinical Trials (ASCEND)","The volume of clinical research in Tanzania has increased rapidly in the last 10 years and so has the demand on research ethics committees and medicines regulators to approve and monitor research. In the same vein the rise in occurrence of highly infectious diseases, such as Ebola, Chikungunya, etc, that have no approved therapy have tested the readiness of ethics committees and medicine regulators across Africa. The need for ethical and regulatory capacity to respond in a timely manner cannot be emphasised more. Through our EDCTP funded SMERT grant (EDCTP-CSA-Ethics-1432-SMERT), some progress has been made resulting in establishment of electronic systems to expedite research ethics review at the National Health Research Committee and reporting of adverse drug events in clinical trials. Despite this progress, there are still substantial gaps that ASCEND will address in order to make Tanzania ready to ensure quality and safety of medicines and performance of Good Clinical Practice (GCP) compliant clinical trials. The concept of research ethics and pharmacovigilance remains abstract to the majority in the community, which consequently compromises the effectiveness of ensuring ethical research and reporting of adverse drug events (ADEs). ASCEND will use the opportunity to sensitise members of the public on their rights and responsibilities to question the ethics of research they are participating in and to report any ADE. Tanzania Medicines and Medical Devices Authority (TMDA) and Muhimbili University of Allied Health Sciences (MUHAS) are Regional Centres of Regulatory Excellence (RCOREs) for medicines evaluation and excellence with a mandate of enabling national medicines regulatory authorities (NMRA) to develop their medicines regulatory capacity. Sadly, the RCORE itself lacks the capacity to achieve their mandate. ASCEND will support the MUHAS/TMDA RCORE to develop human and infrastructural capacity to perform their duties. Harmonisation of medicines evaluation guidelines across East Africa will be proactively sought. Zanzibar, one of the nations that form the United Republic of Tanzania, has recently established their national research ethics committee and medicines regulatory authority, which still require a lot of capacity building to effectively execute their mandated duties. Through ASCEND, ethics committee members and pharmacovigilance monitors will be trained and a mentoring scheme put in place to ensure sustainable capacity building beyond the ASCEND project.",,2023,Tanzania Medicines and Medical Devices Authority (TMDA),583537.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Filoviridae,,,,,,,,,Ebola virus disease | Other,European & Developing Countries Clinical Trials Partnership (EDCTP),International,International,Africa,,,,,Tanzania,,Research to inform ethical issues | Health Systems Research,"Research to inform ethical issues in Governance | Medicines, vaccines & other technologies",2020 +P21267,CSA2020ERC-3081,Côte d'Ivoire Ethics Capacity Building Initiative (CECaBI),"Côte d'Ivoire is located in West Africa. It neighbours Guinea, Liberia, Mali, Burkina Faso and Ghana, among others, with a population of 25 million people. It has a life expectancy at birth of 42 for males and 47 for females. Infant mortality is estimated at 118 of 1000 live births. According to WHO, Côte d'Ivoire has the 27th-highest maternal mortality rate and the 19th-highest HIV/AIDs rate among adults in the world. Furthermore, its proximity to Guinea and Liberia, which are among the countries that were worst hit by the 2014-2016 West Africa Ebola Virus outbreak, make it vulnerable to disease outbreak. Despite this context, Côte d’Ivoire devotes only 0.13% of GDP to Research Innovation and Development (RID). This RID investment has been linked to a myriad of challenges, including inadequate scientific equipment, fragmentation of research organisations and a failure to exploit and protect research results. For example, despite 63.8% of the 2012â€""2015 National Development Plan being devoted to wealth creation and social equity, only 1.2% was allocated to scientific research. This has implications not only on the quality of health research, but on the overall ethics governance and regulatory practices in the country. The national research ethics committee was established in 2001 to advise the MOH on how to promote the protection of the dignity and rights of research participants and assess the ethical considerations of studies before they are implemented. Although Côte d’Ivoire’s research ethics and regulation remains fragile, under-developed and fragmented, it has received limited support for capacitating its national ethics and regulatory practices. The Côte d’Ivoire Ethics Building Initiative (CECaBI) is a consortium of different partners who plan to work together to transform the ethics and regulatory practices in the country by undertaking the following objectives: Undertake a comprehensive needs assessment and benchmarking to identify specific areas of improvement Establish a vibrant research ethics committee secretariat and virtual research ethics committee administrator support Develop an ethics governance framework for institutional REC Provide advanced research ethics training and protection of human research participants Build participants knowledge and skills in Good Clinical Practice and monitoring of approved clinical trials Digitalise REC operations Conduct clinical trials meta-analysis through HRWeb.",,2023,Ministère de la Santé et de l'Hygiène Publique et de la Couverture Maladie Universelle - Cote d'Ivoire,595000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Filoviridae,,,,,,,,,Ebola virus disease | Other,European Commission,Europe,Europe,Africa,,,,,Cote d'Ivoire,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in Governance,2021 +P21270,TMA2017SF-1946,Strengthening vaccine research at CERMEL focusing on biomedical and social sciences (VARSAF),"Aims and objectives The Biomedicine and social sciences group is an interdisciplinary research group I am setting up at CERMEL in Lambaréné, Gabon. Our scientific scope covers vaccine research and social and economic impacts of biomedical research. The current proposal combines biomedical and sociological researches to strengthen vaccine research in sub-Saharan Africa (SSA)settings . The biomedical component of my proposal will assess the extent of reduced responses induced by vaccines among sub-Saharan populations and explore the roles of immune activation and controlled viral replication to improve the design of vaccines for SSA populations. The sociological component will study and strengthen the integration of biomedical research activities by SSA societies. Methods The biomedical research agenda To compare efficacy, effectiveness and correlates of protection induced by childhood vaccines between populations living in SSA versus India, Europe and Northern America using a systematic review and meta-analysis. This will assess whether reduced protection is specific to some vaccines and their components or intrinsic to the SSA populations. To assess the states of immune activation in participants enrolled in vaccine trials before, during and after the course of vaccination on the kinetics of vaccine-induced responses against a VSV vectored Ebola vaccine and attenuated sporozoite based malaria vaccine (PfSPZ) and on the efficacy of PfSPZ vaccine. To study and understand the boosting effect of the VSV vector on the immune responses induced by licensed vaccines The social sciences research agenda To study the degree of integration of biomedical sciences by SSA societies and to propose a framework to evaluate the social and economic impacts of biomedical sciences in SSA societies. Fit with scope and objectives of EDCTP The project aims to generate to improve vaccine immune responses against PRDs . In addition, the project will provide a tool to assess impacts of biomedical research. These objectives address the control of PRDs at both scientific and societal levels. Expected impacts I expect to publish high impact factor papers and attend major scientific meetings. In parallel, I will enter into two professorship programs and set up a monthly seminar with the aim to have it incorporated into a Master or PhD curricula of the future school of public health being implemented in Lambaréné, Gabon. The results will be communicated to stakeholders in Africa. After my fellowship, I will lead regional and international networks with CERMEL.",,2024,"Centre de recherches médicales de Lambaréné, CERMEL",560000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase IV",Filoviridae,,,,,,,,,Ebola virus disease,European & Developing Countries Clinical Trials Partnership (EDCTP),International,International,Africa,,Innovation,,,Gabon,,"Vaccines research, development and implementation | Research on Capacity Strengthening",Characterisation of vaccine-induced immunity | Systemic/environmental components of capacity strengthening,2020 +P21272,1R21EB031306-01,Selectively Replicating Trojan Virus Vectors as Programmable CRISPR-Based Antiviral Therapies,"PROJECT SUMMARY The COVID-19 pandemic has highlighted our long-standing vulnerability to new viral infectious diseases with which there is no acquired immunity. While vaccines and antiviral therapies can eventually be developed to treat many viral infectious diseases, these interventions require significant time and resources to acquire. This results in a critical period of time where there are no therapeutic options to slow the spread of the virus, besides physical countermeasures that have dramatic economic and social consequences. The truly alarming insight is that all of the vaccines and therapies we develop now against SARS-CoV-2 will be useless against the next cycle of viral outbreaks (e.g., influenza, ebola, etc.). There is a paramount need to fundamentally transform our approach to combating emerging viral diseases by developing antiviral strategies that can be rapidly deployed at the onset of a new viral outbreak. We propose a revolutionary new viral-antiviral technology that has the potential to target emerging viral pathogens at all stages of the disease outbreak cycle. This includes targeting viral pathogens in animal hosts prior to human transmission, preventing viral infections in healthy individuals, and treating ongoing viral infections. This new “Trojan virus” technology uses engineered viral vectors that imitate viral pathogens, yet contain potent CRISPR antiviral machinery that degrades pathogenic viral particles. These Trojan virus vectors have an incomplete viral genome that can selectively replicate only in previously infected cells by hijacking viral derived proteins, which it uses to multiply and spread throughout the infected areas of the body. The spread of the Trojan virus acts to prevent viral infection in healthy tissue by targeting invading viral particles, while at the same time suppressing active sites of viral infection. The integration of CRISPR antiviral technology into Trojan virus vectors allows the system to be reprogrammed to target new viral strains without extensive protein engineering or clinical testing, facilitating the rapid mobilization of the technology during viral disease outbreaks. The proposed research will focus on developing SARS-CoV-2 Trojan virus technology as a therapeutic option for active viral infections. The research will use engineered non-infectious cellular model systems to evaluate SARS-CoV-2 Trojan virus genome designs that can selectively replicate only in previously infected cells. We will determine the optimal strategy for incorporating CRISPR antiviral technology into the SARS-CoV-2 Trojan virus vectors, while identifying key CRISPR vulnerabilities in the SARS-CoV-2 virus. To validate that the genome engineering principles developed for the SARS-CoV-2 Trojan virus therapy can mitigate active viral infections, we will duplicate the approach to target the mouse hepatitis coronavirus (MHV-A59), tracking the effectiveness of the Trojan virus in murine model systems. If successful, our research will generate a functional SARS-CoV-2 Trojan virus therapy, validating the genome design in preclinical model systems, to establish the foundation for commercial development of the technology for use in the current and future SARS- CoV outbreaks.",,2023,Unknown,612000,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +P21274,NIHR134531,NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard),Vaccination is a hugely important public health intervention: key to smallpox eradication polio elimination and control of Ebola outbreaks and the COVID-19 pandemic. But not everyone benefits equally. Some vaccines give weaker protection in people from rural tropical settings than in those from high income settings: for example BCG for tuberculosis and oral polio vaccine for polio. Some new vaccines under development also elicit weaker responses in people living in low-income rural settings. The biological reasons for this are not fully understood. Also some people benefit less from vaccines for socioeconomic reasons such as the social context of the communities they live in including limited access to accurate information to aid vaccine choices. Social and biological factors can interact to make communities “vulnerable” in terms of vaccine impact. For example poor people in rural communities with difficulties in vaccine access may also be undernourished or exposed to infections that alter immune responses to vaccination. This needs to be addressed to promote health equity but also to secure maximum global benefit from vaccines: non-immune communities are foci for recurrent disease outbreaks.VAnguard’s goal is to understand how biological and social factors interact to impair vaccine impact in vulnerable African communities in order to develop integrated strategies to optimise vaccine benefits and drive health equity. VAnguard will bring together African and UK experts in vaccine research implementation and stakeholder and community engagement to work in Uganda and Kenya to1.Investigate how biological factors (such as infections nutrition) influence vaccine responses2.Explore how communities perceive and access vaccines what influences them to take up vaccines for themselves and their families and how this relates to social vulnerability biological health status and vaccine information 3.Bring together biological and social data and engage communities to work out how vaccination can best be optimised for vulnerable communities thereby also benefitting entire populations. First we shall work with national stakeholders (such as Ministries of Health and vaccine-related non-governmental organisations) review literature and work on samples from previous studies to identify Ugandan and Kenyan communities likely to have most difficulty in getting the best out of vaccination programmes (“vulnerable communities”). Then with stakeholders and communities we shall co-design the VAnguard Community Study and implement it to investigate in detail which biological and social factors most influence vaccine impact in vulnerable communities. Data and economic modellers will study the results to identify which factors could usefully be modified and we shall work with the communities to explore ways in which this could be done. Hence we shall co-develop strategies which national stakeholders may be able to implement straight away or which can be tested in future studies.The work will be led by young African scientists supported by local and international experts to build capacity for African vaccine research. Biological social and implementation scientists and experts will work closely together to understand each other’s disciplines establishing a culture of collaboration that will foster sustainable pathways to the desired impact: healthy communities.,,2026,London School of Hygiene & Tropical Medicine,3461958.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2022 +P21286,2878551,Antibody discovery for neglected tropical and emerging infectious diseases,"Monoclonal antibody (mAb) therapies are now routinely used as cancer therapies and immunosuppressants. Many mAbs licensed today are so-called 'blockbuster' therapies, with the majority of the Top 10 best-selling therapeutic drugs being mAbs. Until recently, mAbs for infectious diseases have largely lagged behind those for cancer and immunotherapies. However, the increase in demand for therapies, and spurred on by the recent covid pandemic, has led to substantial investments and advances in optimised manufacturing and reducing production costs. As such, there is increasing appetite for investing and developing mAbs for infectious diseases, including emerging infectious diseases and those which predominantly affect LMICs. Using LSTM's and Lancaster University's unique resources, this project will be focused on the development of mAbs for a range of neglected tropical diseases, such as snakebite envenoming and recently emerging infectious diseases including pox viruses (for example, mpox).",,2027,N/A,,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae | Novel Pathogen | Unspecified,,,,,,,,,Mpox | Disease X | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,"Therapeutics research, development and implementation",,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21287,2878968,Antibody discovery for neglected tropical and emerging infectious diseases,"Monoclonal antibody (mAb) therapies are now routinely used as cancer therapies and immunosuppressants. Many mAbs licensed today are so-called 'blockbuster' therapies, with the majority of the Top 10 best-selling therapeutic drugs being mAbs. Until recently, mAbs for infectious diseases have largely lagged behind those for cancer and immunotherapies. However, the increase in demand for therapies, and spurred on by the recent covid pandemic, has led to substantial investments and advances in optimised manufacturing and reducing production costs. As such, there is increasing appetite for investing and developing mAbs for infectious diseases, including emerging infectious diseases and those which predominantly affect LMICs. Using LSTM's and Lancaster University's unique resources, this project will be focused on the development of mAbs for a range of neglected tropical diseases, such as snakebite envenoming and recently emerging infectious diseases including pox viruses (for example, mpox).",,2027,N/A,,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae | Poxviridae | Unspecified,,,,,,,,,Nipah and henipaviral disease | Mpox | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,"Therapeutics research, development and implementation",,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21289,BB/X011607/1,Monkeypox Rapid Research Response,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,University of Glasgow,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,,,2022 +P21290,BB/X011143/1,[Monkeypox] Rapid Research Response,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,University of Cambridge,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,,,2022 +P21291,ES/X010805/1,Social Science issues relating to Monkeypox,"This project proposes scoping primary qualitative research in the form of roundtables and a narrative evidence review to explore community organising and information sharing among MSM during monkeypox, the influence of social media, and the role of underserved communities. With this data, this project will identify lessons for future communication, explore the role of social media and highlight dynamics of exclusion. It will produce highly policy-relevant evidence-based recommendations that answer the needs identified in the IPPO stage 1 report.",,2023,University College London,183238.26,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Data Management and Data Sharing,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations,United Kingdom,,"Policies for public health, disease control & community resilience",Communication,2022 +P21292,BB/X011542/1,[Monkey Pox] Rapid Research Response,"The project proposes a rapid response to the current monkeypox virus (MPXV) epidemic. It is led by the Pirbright Institute and the Centre for Virus Research - Glasgow - the two UKRI-funded institutes that lead on virus infections of animals and humans - and brings together relevant expertise from several other UK universities and institutions including the Universities of Cambridge, Oxford, Birmingham, Edinburgh and Surrey, Dstl, UKHSA, Guys and St Thomas NHS. Between April and 18th July 2022, there have been 2137 confirmed cases of human monkeypox (MPX) in UK and the WHO has reported infections in all 5 WHO regions and 50 member states. The current epidemic is the largest ever known for MPXV. An urgent response to this growing epidemic is needed. The consortium assembled proposes 6 inter-related work packages as follows. 1. Genomic characterisation of MPXV. 2. Examination of possible virus spillover from humans to UK animals 3. Study of the intrinsic and innate barriers to MPXV infection, and MPXV immune evasion strategies 4. Study of the immune response to MPXV infection and vaccination 5. Development of anti-viral drugs and monitoring for emergence of MPXV drug resistance 6. To develop point of care diagnostic tests for MPXV WP 1. This will undertake sequencing of MPXV genomes isolated from humans in UK and monitor virus evolution and adaptation to humans. The sequencing will pay particular attention to the acquisition of genome mutations that might affect virus replication, transmission, virulence or drug resistance and links to WP5. WP2. MPXV has a natural reservoir in rodents in parts of Africa and has a relatively broad host range that includes North American rodents, primates and humans. The widespread human infections provide a possible opportunity for human to animal transmission. This WP will evaluate this potential by examining the ability of MPXV to infect primary cells from a variety of UK animals. WP3. This WP will evaluate the host response to infection by measuring the transcriptomic and proteomic responses to infection of human cells and testing the roles of specific host proteins in protecting against MPXV infection. Further, the ability of MPXV to counteract these defences will be tested building on what has been learnt from studies of related orthopoxviruses. WP4. The immune response to MPXV infection of humans will be measured by determining the antibody and T cell responses. These will be compared with the responses to vaccination using the smallpox vaccine. A specific aim will be to identity signature T cell responses that are characteristic of MPXV infection. In addition to information vaccination programmes, the development of specific tests for immune monitoring will be undertaken. WP5. This WP is concerned with the development of anti-MPXV drugs and builds on the development of CRUSH (COVID-19 Drug Screening and Resistance Hub) at CVR-Glasgow. Currently, 2 drugs are licensed for use against MPXV and these each target a specific virus protein, but mutation of these proteins can lead to drug resistance. The WP proposes to screen additional FDA-approved drugs that have activity against VACV for activity against MPXV. Cyclosporin A and non-immunosuppressive derivatives will be included since these target a proviral cellular protein, cyclophilin A, and therefore emergence of virus resistance is difficult. WP 6. This will develop point of care (POC) diagnostic tests for MPXV. Currently, MPXV infection is confirmed by polymerase chain reaction (PCR), which is specific and sensitive but requires a specialist laboratory. A POC test (such as developed for SARS-CoV-2) would be of great benefit to speed diagnosis. Two approaches will be tried: a Lateral flow test (LAT) and a loop-mediated isothermal amplification (LAMP)-based assay.",,2023,N/A,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Innovation,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Therapeutics research, development and implementation | Vaccines research, development and implementation","Development of equitable, accessible, safe & effective diagnostics (including POC) | Research for enhanced understanding of the disease | Viral evolution in different contexts & implications | Investigation of zoonotic transmission & reservoirs | Development of equitable, accessible, safe & effective therapeutics | Development of equitable, accessible, safe and effective vaccines",United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Therapeutics research, development and implementation | Vaccines research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Vector biology | Prophylactic use of treatments | Pre-clinical studies | Characterisation of vaccine-induced immunity",2022 +P21293,BB/T006501/1,Viral manipulation of DBC1: a novel strategy to promote cell survival and suppress inflammation,"Human and animal cells have very sophisticated networks to communicate and respond to stress. Infection by a virus is a stress that can lead to the death of the cell. Accordingly cells respond vigorously to viral infection with the aim of blocking viral multiplication and alerting the body's immune system to the ongoing infection. Only viruses that have the capacity to avoid this hostile cell response survive. How viruses achieve this is not always clear. However, if and when one of these viral strategies is discovered, an opportunity for the development of antiviral interventions emerges. This project concerns the discovery of one of those strategies employed by a group of viruses named poxviruses, a member of which was responsible for the devastating disease smallpox. The smallpox virus killed more people in recorded history than all other infectious diseases combined, but fortunately was eradicated thanks to a worldwide vaccination campaign that used vaccinia virus (VACV), another member of the poxvirus family. VACV is currently being studied as a vaccine against another smallpox-like disease known as monkeypox as well as other several important human and animal diseases such as tuberculosis, AIDS, or rabies. This project will study how poxviruses manipulate the activity of a cellular protein termed DBC1. DBC1 belongs to one of those communication networks that cells use to respond to external stress. Its main role is to block the action of another protein known as SIRT1. Both DBC1 and SIRT1 were only discovered ~10 years ago, so our understanding of how they work is still in its infancy. However, it is now clear that both DBC1 and SIRT1 are very important in the process of ageing and in age-related diseases such as cancer and chronic inflammation. This project demonstrates that poxviruses specifically bind and relocalise DBC1, the negative regulator of SIRT1, in a part of the cell where SIRT1 is not normally present. This suggests that poxviruses break the DBC1-SIRT1 connection and benefit from this in a number of ways that are not fully understood yet. This project will therefore determine 1) how poxviruses sequester DBC1 away from SIRT1, 2) what advantage this has for the virus, and 3) what consequences this viral action has in disease and vaccination. To address how, detailed molecular biology and protein localisation studies will be developed. To address why, we will conduct a series of functional tests in cells previously modified to lack DBC1, SIRT1 or both genes. The response of these cells to infection will be studied and compared to that of normal cells. The conclusions from these studies will establish for the first time the role of the DBC1-SIRT1 axis during infection with viruses, and will provide valuable information not only for emerging poxviruses such as the monkeypox virus, but perhaps also for other viruses with similar biology such the African Swine Fever virus - an emerging, economically important pig pathogen that might also sequester DBC1. Finally, given the importance of VACV as a vaccine, the project will study the impact of the DBC1-SIRT1 axis in vaccination using viruses modified in the laboratory to relocate DBC1 or not. The response to vaccination is known to be complex and to change with age. If the modified virus that does not break the DBC1-SIRT1 connection triggers a better immune response, this modification can be introduced into VACV-based vaccines that are currently being developed. Therefore this project has the potential to impact on the design of vaccines and to improve our understanding of ageing and its biology.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21294,10045699,Float Photon - The SpacePad,"The pandemic has highlighted the transmissibility of respiratory particles onto surfaces from one person and then from hand to face by another. e.g. Covid-19, Monkeypox, flu. Current WHO and NHS Covid guidance recommends avoiding contact with surfaces in public places. This is especially pertinent in health care settings such as hospitals and GP surgeries where vulnerable and sick people frequent. The current rapid adoption of touchscreen displays in the NHS for patient and visitor interaction is driven by cost saving efficiencies. However, this adoption has brought a new challenge of infection control as these touchscreens are high frequency touch items by diverse members of the public. Current mitigation techniques are unsatisfactory. The most common is the clean after every user philosophy that leads to reduced efficiency and a massive increase in biohazard waste that creates an environmental problem that is not carbon neutral. The repetitive cleaning also damages the equipment. Other methods like sterilisation by UV light is not fully effective as certain bacteria survive exposure. There is a clear need for a non-burdensome, cost effective, zero transmission human interface that is non-waste creating and carbon neutral. The Float Photon Interface (FPI) is such a solution. This disruptive technology floats the human interface in space so there is no user contact and no surface pathogen transmission. FPI is a new disruptive 3D interactive technology that takes advantage of recent advances in manufacturing equipment to bring down the cost of real-time 3D images without glasses to consumer level for the first time. The algorithm and software development already done leapfrogs expensive holographic and light field solutions and is demonstrable as proof of concept bringing what was science fiction into science fact.",,2023,TEMPORAL RESEARCH LTD,58000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Infection prevention and control,,2022 +P21295,MR/X013588/1,High-throughput digital microplate microscopy reader for the study of cellular responses to infection and stress,"Viruses require living cells to multiply. When doing so, viruses cause a complete re-organisation of the infected cell, overall allowing the production of thousands of new viral particles but also suppressing the ability of the host to fight infection. Crucial insights into this complex interplay can be obtained imaging living cells and viruses, which is only possible using microscopes. Most microscopes are, however, able to image a few cells at a time making it very lengthy and laborious to obtain information from a representative number of cells. In addition, cells undergo their own life cycle and variations exist between them even in the same petri dish. A way to overcome this problem is the use of high-throughput microscopes able to image thousands of cells and analyse their properties on an individual basis. This proposal concerns the acquisition of one of such imaging systems for the Section of Virology at the University of Surrey, a unit of research formed by >20 investigators from 6 different groups studying human viruses and their interplay with human cells. The instrument we propose to acquire will enable us to track where viruses go inside a cell and how they manipulate the intracellular environment. We will be able to visualise viral features such as gene expression and replication factories, as well as the cell's response to infection in the form of stress granules, mitochondrial reorganisation and cell and nucleus morphology. More importantly, we will be able to measure these events qualitatively and quantitatively in hundreds of individual cells in specified conditions, generating high quality reproducible data in a short period of time. As examples, we have recently discovered a viral protein expressed in poxviruses (including the emerging monkeypox virus) that induces the clustering of mitochondria (the energy factories of the cell). The kinetics of assembly and disassembly as well as the size and morphology of these clusters in different conditions remains unknown but can be elucidated with a high-throughput multimode microscopy unit. Similarly, we have recently discovered that cells infected with herpes simplex virus fail to export their mRNAs from the nucleus, causing a blockade of cellular functions that allows efficient virus infection. The mechanisms behind this process are unclear but can be researched with an imaging system equipped with a spot counting module. Altogether the requested instrument will not only increase our capacity to deliver ground-breaking research, but also provide novel perspectives on viral infection that are at present not possible with other equipment.",,2023,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae | Unspecified,,,,,,,,,Mpox | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21306,MR/W010690/1,Opening new windows into viruses inside the cell by electron cryo-tomography (cryo-ET),"As the Caltech physicist Richard Feynman once explained, ""It is very easy to answer many fundamental biological questions; you just look at the thing!"". If we could simply look at a virus inside a eukaryotic cell and observe all the host and virus molecules interacting with one another in their native state, we would vastly improve our understanding of the virus life cycle and the cellular innate immune responses. In fact, several key historical breakthroughs in virology and cellular biology have been made through advances in imaging technologies. The development of traditional electron microscopy (EM) led to the first detailed pictures of a virus and later the fine ultrastructure of cellular organelles such as the Golgi apparatus and endoplasmic reticulum. Successive technological advances have brought us to the point that we are able to image viruses at close to atomic resolution, a feat recognized by the 2017 Nobel Prize in Chemistry 'for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution"". With recent electron cryo-tomography (cryo-ET) technology developments, we are in touching distance of visualizing any virus in its native state and context within the cell. For the first time, all stages of a viral replication cycle from attachment and entry through genome replication to morphogenesis and egress may be visualized at macromolecular resolution. This is an exceedingly exciting moment to work in this field. This new technology affords us the opportunity to solve the structure of viral proteins in their natural habitat with unprecedented resolution. To understand virus-host interactions using cryo-ET technology I am proposing to address a number of important biological questions targeting the virus order Bunyavirales. Viruses in this order are representative of many emerging viruses which pose a high-risk to human and animal health. In cryo-ET, samples are plunged into a cryogen (liquid ethane, or a mixture of ethane and propane), preserving them in a frozen-hydrated, near-native state. The frozen samples are then imaged in a transmission electron microscope, and a series of 2-D projection images are recorded as the sample is rotated incrementally around an axis. This so-called ""tilt-series"" is then reconstructed into a 3-D ""tomogram"", with typical resolution sufficient to make out the shapes and arrangement of large macromolecules (~5 nm). If the tomogram, or a set of tomograms, contains structurally homogeneous copies of an object of interest, ""tomogram subvolumes"" containing the objects can be computationally extracted, aligned and combined, a process we call ""subtomogram averaging"" (STA) to improve the signal-to-noise ratio and clarify details, typically improving the resolution to ~2-3 nm. For exceptionally favorable samples such as pseudo-crystalline protein coats on cells or viruses, the resolution of STA can be pushed to even 3.1A, sufficient to build atomic models de novo. To learn about important aspects of Bunyavirales biology, my research will apply state of the art technologies, such as cryo-CLEM, cryo-FIB milling, cryo-ET and STA to visualize infection of the related viruses TOSV and RVFV (Phenuiviridae) in situ at high-resolution. Using these techniques, I will look for novel structural aspects of both the pro- and antiviral processes that take place during the immune response and the triggering of the antiviral innate immune response of the cell. More specifically I will investigate (i) restriction of the virus RNPs by the MxA restriction factor, and (ii) the architecture of TOSV and RVFV host response antagonist NSs filaments inside the nucleus. Identifying new structures and key interactions between the virus and the host will be a step change in understanding fundamental aspects of viral replication and the host antiviral responses and might even allow for new insights into host targeted therapeutics.",,2026,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21307,2888136,"'Understanding viral zoonotic spillover through an integrated eco-epidemiological approach, using Crimean Congo Haemorrhagic Fever virus (CCHFV) in Ug","Viral zoonoses represent an important reservoir for emerging and remerging viral infections, resulting in significant health and economic costs through spillover events causing human infection. These spillover events are the result of a complex combination of virological, socioeconomic and ecological factors and understanding and predicting spillover requires a multidisciplinary approach encompassing human, animal and environmental health. There is also an urgency to understand how ongoing global environmental changes will impact upon the risk of zoonotic spillover. Uganda has been identified as a potential high-risk area for emerging infections due to its rich biodiversity and other specific ecological and social features of the region, that remain poorly understood. CCHFV is an orthonairovirus; it undergoes a silent sylvatic cycle in nature which includes ixodes ticks as both the principal virus reservoir and vector and wild mammals acting as important amplifying hosts. In endemic areas, livestock are commonly infected and may act as bridging hosts, enabling human spillover events. Infection in humans causes a spectrum of disease; ranging from subclinical infection to severe haemorrhagic disease with a mortality rate of up to 40%. Humans are infected through tick bites or exposure to blood from infected animals, however the wider factors determining spillover and severity of human disease remain poorly understood. CCHFV has been detected in ticks, livestock and humans in Uganda, and previous small seroprevalence studies have indicated high levels of exposure in livestock and at-risk human populations. However, the true burden of disease is unknown due to lack of systematic surveillance and underdiagnosis of acute infection. CCHFV is known to demonstrate significant geographic genetic diversity which may have implications for transmission, disease severity, diagnostic testing and breadth of immunity between strains. My thesis will bring together field epidemiology, serology, next generation sequencing and bioinformatics and ecological methods, to better understand the risk of CCHFV in Uganda. This will directly inform future surveillance and prevention strategies and lessons learnt from this combined approach can be applied to other zoonotic and vector borne infections.",,2026,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Vector biology | Disease transmission dynamics",2023 +P21310,2879796,Hacking at the cellular level; How do viruses subvert intracellular networks for viral RNA genome trafficking within infected cells?,"Nairoviruses are a group of insect-borne RNA viruses that include the extreme human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV), which is listed as a priority pathogen in the WHO 'Research and Development Blueprint'. No vaccines or therapies are currently available to prevent or treat CCHFV disease, and this represents an urgent unmet need. Nairoviruses are enveloped viruses that internalise into cells within endosomes, and following endosome-escape, their RNA genomes transit to a specific destination. This transit does not occur by random diffusion - instead nairoviruses subvert cellular process to move their genomes to a site known as a viral factory. As its name suggests, the factory is the site of intense anabolic activity, where viral components are mass-produced, destined for assembly into new viruses. Formation of the virus factory is a multi-step process, critical for infection and disease. However, no detailed information of how the nairovirus genome transits to the factory site, or factory structure, is currently available. This project will fill this knowledge gap, providing potential cellular and viral targets for future anti-viral therapies, as well as providing detailed information of critical host-pathogen interactions. Using the closely related yet non-pathogenic Hazara nairovirus (HAZV) as a model for CCHFV, this project will identify cellular pathways and components that are hijacked by nairoviruses to allow their journey from the endosome to the virus factory, as well as determine the location and ultrastructure of the factory itself. To achieve these aims, we will first use reverse genetics to introduce site-specific mutations within the HAZV RNA genome to develop a 'tool-kit' of engineered infectious HAZV variants bearing genetically encoded fluorescent and epitope tags, which will allow visualization and tracking of all HAZV RNA and protein components within cells on the entry pathway. Next, using our previously generated RNAi and CRISPR-based gene knock-down/knock-out screen data (Fuller et al, 2020), we will determine cell factor involvement by visualizing impaired RNA genome transit in cells with disrupted protein function, resulting from genetic ablation or use of specific inhibitors or expression of dominant-negatives. Finally, we will visualize virus factory organisation using electron microscopy observation of sectioned cells, using state-of-the-art cryo-focused ion beam, alongside high-resolution light microscopy techniques such as STED. We recently characterised for the first time the location and content of the hantavirus replication factory using light and electron microscopy (Davies et al, 2020) and similar techniques will be adopted here.",,2027,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies",2023 +P21311,BB/W010755/1,"20-EEID US-UK Modelling reassortment at the cellular, clinical, and phylogenetic level in emerging Bunyaviruses","Genome segmentation has important implications for viral gene expression control and RNA assembly into nascent virions. It also creates the potential for reassortment: the exchange of intact gene segments between viruses that coinfect the same cell. Reassortment is quantitatively different from intramolecular recombination in that it allows many distinct genotypes to emerge from a single coinfected cell. Not only does segmentation enhance genetic diversification but it also plays a unique role in the evolutionary history of many segmented viruses due to the rare occasions when a reassortant is successful at the population scale. A striking example of the emergence of a novel virus through reassortment from the Bunyavirales is that of Ngari virus. For influenza (IAV), the best characterised segmented virus, reassortment has facilitated the formation of pandemic strains in 1957, 1968 and 2009. Out of seven epidemic-prone diseases prioritised by the WHO 2018 R&D Blueprint as public health emergency with an urgent need for accelerated research, three are Bunyaviruses. Thus, the overarching hypothesis of this project is that reassortment of segmented viruses plays a major role not only to drive their diversification and evolution, but to dramatically alter their ecology and transmission dynamics. Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses and together with in vitro experiments quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised protocols for sequencing, as well as novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV). A biobank with clinical and field samples from key CCHFV endemic regions in Turkey and Tajikistan will be set up in this project. Clinical and field data will be leveraged so that our methods and results have the potential to inform control strategies and predict outbreak risk. The quantitative methods developed in this project will contribute to the One Health approach advocated by Sorvillo et al. for CCHFV. Our goal is to develop novel mathematical and phylodynamic methods to quantify, at the cellular and the epidemic levels, reassortment frequency and fitness for segmented Bunyaviruses. This will enhance our understanding of CCHFV evolution and epidemiology in Turkey and Tajikistan. To achieve this goal, this US-UK collaborative project brings together expertise in phylogenetics, mathematical modelling, BSL-3 and BSL-4 capabilities, as well as field and clinical expertise in Turkey and Tajikistan with direct access to large collections of human, animal host and vector samples. We will quantify reassortment patterns, bringing together mathematical models with in vitro experiments of selected Bunyaviruses in arthropod and vertebrate cell lines. Statistical inference will allow us to estimate the basic reproduction number for each reassortant and cellular host. At the population level, we will design DNA sequencing and phylodynamic methods to dissect the evolutionary and transmission history of a segmented virus. Thus, our phylogenetic analysis of the field data to be collected in Turkey and Tajikistan will critically evaluate the convolution of point mutations, recombination and reassortment of CCHFV. Phylodynamic methods, adapted and developed in this project, together with field data, will allow us to relate these evolutionary processes to the host switching, temporal and geographical patterns of CCHFV outbreaks. With clinical information and data from Turkey and Tajikistan we will parameterise a mathematical model of CCHFV nosocomial transmission to inform public health decision making. While we focus on the Bunyaviridae family, especially CCHFV, our quantitative methods will be made adjustable to other segmented viruses of great public health relevance.",,2025,N/A,,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2022 +P21312,105675,Development of improved tests for detection of Rift Valley fever virus antibodies,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2022,"Innovate UK, Kenya Agricultural and Livestock Research Organization, University of Nottingham, RSK ADAS LIMITED",297145.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,UK Research and Innovation (UKRI),United Kingdom,Europe,Africa | Europe,,,,,Kenya | United Kingdom | United Kingdom | United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21313,MC_UU_00033/2,Vaccinology,"Vaccines are among the most successful tools available for protecting public health, but effective vaccines are still lacking for many infectious diseases that are important in Africa â€Â"" including HIV, viruses that cause major outbreaks in African populations, and parasitic diseases including worm infections. As well, vaccines work better in some communities than others, with poor communities in rural, low-income, tropical settings often at a disadvantage. Our theme will contribute to • Developing new vaccines of particular importance for Africa, and testing them in clinical trials â€Â"" for example vaccines against viruses such as Rift Valley Fever which causes outbreaks among humans and farm animals in East Africa, and against debilitating worm infections such as schistosomiasis • Understanding how best to employ vaccines in Africa â€Â"" for example how vaccines can be combined with other preventive measures against HIV, or what the most appropriate dosing schedules are for particular age groups and needs • Investigating why some vaccines work differently in different communities, and working with communities to develop strategies that enable them to benefit from vaccines to the full • Understanding how different communities learn about, understand and perceive vaccines, and what makes people confident to use them • Building vaccine research expertise among African researchers This work will contribute to ensuring that African communities secure the maximum possible benefit from vaccines.",,2028,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Bunyaviridae,,,,,,,,,Rift Valley Fever,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Vaccine/Therapeutic/ treatment hesitancy,2023 +P21318,10027019,Oral Nipah Vaccine,"IosBio has developed a technology which enables the generation of thermally stable, orally administered vaccines. We will utilise this technology to develop a candidate Nipah vaccine, a disease identified as having pandemic potential.",,2023,"IOSBIO LTD, Innovate UK",378076.48,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Innovation,,,United Kingdom | United Kingdom,,"Vaccines research, development and implementation",Vaccine design and administration,2022 +P21319,2741987,DTP 2022 The Rosalind Franklin Institute,Investigating the mechanism of Nipah Virus-Host Cell Membrane fusion using electron microscopy imaging techniques,,2026,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21321,10025020,GMP Manufacture of a vaccine targeting a viral hemorrhagic fever,"Marburg virus disease is indistinguishable from disease caused by Ebolaviruses and is associated with a high case fatality rate. Marburg virus has caused disease outbreaks predominantly in Eastern and Central Africa, with eleven incidences of outbreaks on record between 1975 and 2021\. The location of the most recent Marburg virus outbreak has caused concern regarding viral spread into Western Africa as previous outbreaks have been limited to Kenya, Uganda and the Democratic Republic of the Congo. Marburg virus has been identified as a virus of pandemic and epidemic potential. There are no clinically available vaccines that can protect against disease caused by Marburg virus. Our vaccine modality of choice, for vaccine manufacture, is a chimpanzee adenoviral vector (ChAdOx1). ChAdOx1 regimens are highly immunogenic, and we have demonstrated they can induce protection against disease (e.g. the Oxford/AstraZeneca ChAdOx1 nCOV-19 protects against COVID-19). Of note, the emergency response against COVID-19 has led to large-scale manufacture of this vaccine technology and there is now an accumulated manufacturing experience to generate vaccines at scale and at a price which can be used in low and middle income countries. We have started to generate a vaccine against Marburg virus and in this application we will progress this vaccine through GMP (Good Manufacturing Practice) production - generating a vaccine that can be used in humans to protect against viral haemorrhagic disease. We now wish to progress the ChAdOx1 Marburg to allow for release of the ChAdOx1-Marburg vaccine which is of utmost importance given the outbreak of Marburg virus in Equatorial Guinea and Tanzania and the selection of ChAdOx1-Marburg vaccine by the WHO prioritization committee.",,2023,"Innovate UK, University of Oxford",982376.86,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Marburg virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom | United Kingdom,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase),2022 +P21326,2757382,Responses to Lassa fever disease in Nigeria: a multilevel ethnography of a health system.,"Lassa fever (LF) is a deadly viral haemorrhagic fever endemic to West Africa. Nigeria has experienced outbreaks of increasing severity, despite growing prevention and response efforts deployed by national and international actors. This disconnect between increased health systems and scientific activity alongside an increasing disease burden requires a close examination of how strategies and programmatic actions are designed and implemented, how on-the-ground realities are addressed, how strategies are informed by epidemiological knowledge, and how policymakers navigate between national and global agenda priorities. This study will draw on health systems research and epidemiological research in addition to anthropological approaches, to examine how health system actors organise LF response strategies in Nigeria. I will conduct a multilevel ethnography at the interfaces of different 'levels' of the health system (the policymaking 'level' and the healthcare delivery 'level') in hotspots of previous LF outbreaks. Through a stakeholder analysis of the actors involved in LF response, in-depth interviews, and participant observation in the policymaking and healthcare delivery spheres, this study will contribute to improved understanding of LF responses in Nigeria and will help identify obstacles from design to implementation. Findings will be applicable to other emerging infectious diseases and will contribute to improved understanding of how health systems respond to outbreaks (such as SARS-Cov-2). Moreover, this study will provide insights into how the production of epidemiological knowledge and the organisation of a health system influence one another. From a methodological perspective, this innovative study will promote the use of interdisciplinary approaches in health systems research.",,2026,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health leadership and governance,2022 +P21327,2878021,The Dynamics of Liquid Organelle Re-modelling in Response to Virus Infection,"Liquid organelles are membrane-less compartments that provide an environment for different cellular processes. As such, they can be hijacked by viruses to enable virus replication. Arenaviruses are simple viruses that express only 4 proteins and form a type of liquid organelle (termed stress granule) during infection. Additionally, they are medically relevant viruses, as some cause haemorrhagic fevers (like Lassa virus). This project aims to understand how liquid organelles are formed, which is an emerging and poorly understood topic, by studying arenavirus-induced stress granule formation. To achieve this, the project will first determine the composition of Arenavirus-induced stress granules, comparing it to stress granules from non-infected cells. It will establish an in vitro stress-granule system, which will be manipulated by adding viral components (proteins and RNA) and/or by changing the ionic conditions (reflecting physiological changes occurring during infection). Overall, the project will allow an understanding of this essential viral process, providing possible targets for future therapeutics.",,2027,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21328,BB/W006162/1,Viral entry at the human-animal interface; dissecting the pan-tropic nature of zoonotic viruses.,"Anthropogenic shifts in patterns of land use, habitat infringement and climate change increase the probability of viruses such as SARS-CoV-2, the causative agent of Covid-19, spilling over into humans and/or animals. In turn, increased urbanisation and global travel, the absence of herd immunity and poor preparedness can contribute to turn a localised epidemic into a global pandemic. However, not all viruses in nature appear to share the same propensity to spill over; some are restricted to individual hosts while others have a broad host-range and represent a much greater risk to humans and/or animals (livestock, pets and wildlife). Developing a better understanding of the factors that determine the 'zoonotic potential' of viruses is especially prescient as we look to improve pandemic preparedness in a post-Covid-19 landscape. One of the most important factors to understand in this context is how viral entry (the process whereby the virus attaches to and invades a host cell) correlates with zoonotic potential. In general viruses use specific receptors (proteins or sugars) to enter cells. These can vary between hosts, representing an important point of restriction that directly influences host-range and the potential for spill over. Developing an understanding of this relationship for whole taxonomic groups of viruses (genera or families) will help scientists and stakeholders to assess which viruses represent the greatest risk to humans and animals. Characterising virus receptor usage and host-range at a broad level is technically challenging. For instance, choosing viruses which accurately represent the overall diversity of their family is prone to bias, favouring established pathogens over those isolated in their natural bat or rodent reservoirs. To address this, we have developed and optimised a pipeline which utilises bioinformatic algorithms to unbiasedly select representative viruses. Within this project we will use this approach to characterise the zoonotic potential of the coronavirus and arenavirus families. All human coronaviruses, as well as many of the coronaviruses which infect our pets and livestock, are thought to have a zoonotic origin (bats or rodents). The same is true for the arenaviruses, with viruses like Lassa continually spilling over from their rodent reservoirs. As proof-of-principle we have already gathered this dataset for the morbillivirus genus, uncovering a number of interesting restrictions which may explain the narrower host range of this smaller group (genus) of viruses. Our experimental pipeline will proceed as follows: Once we have selected representative viruses, we will use a range of state-of-the-art techniques to quantify their receptor usage and host-range. Subsequently, we will use mutagenesis and protein-binding experiments to dissect the genetic determinants of this zoonotic potential. The assembled scientific research team has a longstanding interest in this area, with broad and overlapping interests in the morbillivirus, coronavirus and arenavirus families. Previously, we have identified amino acid changes in animal morbillivirus attachment proteins which convey tropism to human receptors, solved the structures of arenavirus attachment proteins and more recently examined the likely bat-origin of SARS-CoV-2. The information we generate in this project will be used to improve our pandemic preparedness, helping us to identify high risk pathogens with broad host-ranges (based on entry). Ultimately this information could be used to design new drugs and vaccines, hopefully preventing future disease in humans and animals.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Immunity | Animal source and routes of transmission",2022 +P21329,10025432,International Serological Standard for Plague,"Whilst many people think of Plague as a disease only found in history books, each year globally several thousand people contract the infection which is caused by the bacterium _Yersinia pestis_. This infection is usually transmitted to people through a bite from an infected flea, although in outbreaks, droplets exhaled from infected people directly infect the lungs of recipients. Fortunately, infections may be treated effectively with antibiotics. However, in the countries worst affected: Congo, Peru and Madagascar, access to medical care is not straight forward. Moreover, there is the risk of the bacteria acquiring antibiotic resistance, which would make current treatment worthless. Whilst vaccines have been developed, they are not recommended by WHO, so the development of new, safer and more efficacious vaccines is essential. A major challenge in the development of vaccines for dangerous diseases like Plague is the need to perform key experimental studies in high bio-containment laboratories. This is very expensive and deters vaccine developers from working on these diseases. What is known is that convalescent patients who have recovered from infection have antibodies in their blood that protects them on re-exposure. Vaccines need to stimulate these antibodies safely. However measuring these protective antibodies is not straightforward. What is needed is a way of harmonising this measurement. The National Institute for Biological Standards and Control (part of the UK Medicines and Healthcare products Regulatory Agency) has a 45-year track record of producing and supplying reference materials that harmonise measurement of antibodies to infectious diseases. Many of these reference materials have been established by the World Health Organisation (WHO) as International Standards -- the primary measurement ""yardstick"" for measuring antibodies. In this project, NIBSC will collaborate with Defence Science Technology Laboratories at Porton Down, with their specialist containment laboratories and the Institute Pasteur, Madagascar, where 75% of plague infections have occurred in recent years, to develop an antibody reference standard for Plague. Experimental data will be submitted to the WHO so it can be accorded the status of International Standard. The goal is to have this done within 12 months, which would be remarkably fast considering the practical challenges. The availability of such a material will support vaccine developers like the Oxford Vaccine Group who have candidate plague vaccines entering clinical trials. If this and other experimental vaccines pass the scrutiny of regulators, then there really is a chance that Plague will become a story from history. Given the extended time frame to secure ethical approval for collection of materials in Madagascar the project is ongoing.",,2023,"Medicines and Healthcare products Regulatory Agency, Innovate UK",251720.43,Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,,,,United Kingdom | United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation | Health Systems Research","Immunity | Characterisation of vaccine-induced immunity | Medicines, vaccines & other technologies",2022 +P21330,2444379,Mathematical and computational plague hazard assessment,"Context of research The risks to civilians and military personnel from biological threats, whether from naturally occurring diseases or malicious attacks, are among the highest priorities for the UK Government. Aims and objectives The aim is to devise mathematical models and computational tools that can be used to support research into the treatment of dangerous pathogens and simulate the dynamics of the competition between interacting populations of pathogens and immune cells within host organisms. The agent of interest in this project is Yersinia pestis (Y. pestis), which is a gram-negative bacterium and the causative agent of plague, a disease of humans and mammals which has been recognised since antiquity. Due to its persistence as a threat from numerous perspectives (public health, defence and security), research is necessary to develop a greater understanding of the dynamics of Y. pestis infection. Since it is highly pathogenic and can only be handled at the highest levels of biological containment in laboratories, very few organisations are able to work with plague. However, there is a substantial amount of published data, and the industrial sponsor (Dstl) possesses a great amount of subject matter expertise. Potential applications and benefits This PhD project aims to develop new within-host mathematical and computational models to describe the process of Y. pestis infection acquired via the inhalation route, and its treatment. The partnership between Dstl and University of Leeds to develop innovative within-host models of infection and treatment of Y. pestis therefore presents an important and exciting challenge for a PhD project. The models will be integrated to provide a toolset that can be used to predict the consequences of an aerosol release of Y. pestis, and to investigate optimal treatment strategies. The toolset will allow different medical countermeasures to be tested in silico and will also allow alternative scenarios, such as antibiotic resistance, to be explored. The research project is aligned with the Health and Global Challenges research theme at the University of Leeds Qualification to be attained: Ph.D degree in Applied Mathematics",,2024,N/A,,Bacteria | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2020 +P21331,NE/W003449/1,Soil survival and re-emergence: the continued threat of plague,"Yersinia pestis (Y. pestis) the bacterium responsible for plague, is probably the most devastating infectious diseases known to humanity and may be responsible for more human deaths than any other micro-organism in history (e.g. during the Black Death). Its 'success' is attributed to the fact that it is extremely contagious, and when untreated, death normally occurs in 1-2 days from bubonic, pneumonic or septicaemic plague. Rodents, fleas and person to person pneumonic transmission are generally considered as fundamental to its rapid spread and although elegant, several facts are inconsistent with this hugely oversimplified model. For example, it is clear that plague can vanish from an epidemic area, only to undergo a resurgence, months or often decades after the original outbreak ceased. Where plague resides during these periods of absence from host and vector populations, and what causes it to re-emerge, has not been studied in detail. Some Y. pestis strains have now acquired multi-antibiotic resistance and an upsurge in transmission of these strains would pose a severe risk to human health, so we need to understand the conditions that might cause a significant re-emergence event to occur. Y. pestis evolved from a near identical, free-living soil-borne ancestor, Yersinia pseudotuberculosis, and soil is therefore thought to be a reservoir for Y. pestis, but how it survives in, and then spreads from this environment has not been adequately investigated. Y. pestis may be protected during this soil stage of its life cycle by embedding in a self-derived protective 'slime' layer (biofilm) enabling the bacterial cells to form a protected association with other bacteria, amoebae or nematodes in the soil. In this study we focus on soil as the important environmental reservoir in which Y. pestis adopts a 'sit and wait' survival lifestyle from where it can re-enter the rodent/human population when conditions are favorable. We aim to identify the environmental and biological triggers that underpin plague survival in, and re-emergence from, soil. To do this we need to take a wide view of the soil environment including factors such as microclimate, soil type, and land cover in association with testing the impact of nematode worms and amoebae on plague survival. Our work will plug a significant and potentially dangerous gap in our understanding of plague ecology, especially important given that the World Health Organization has recently classified Y. pestis as a re-emerging zoonotic pathogen. Using Madagascar as our case study, due to its well recorded plague outbreak history, we will address this knowledge gap using a wide range of scientific approaches. We will use computer based modeling techniques to enable us to predict how plague remains silent for long periods before re-emerging as a new disease outbreak. The model inputs will be obtained by measuring rodent burrow temperatures, humidity and local climate conditions in Madagascar, in conjunction with climate, land cover and soil-type datasets. The models will also use data from Y. pestis soil survival experiments which we will obtain under controlled laboratory conditions. We will also use genetic sequencing techniques to investigate the bacterial soil populations that co-habit with Y. pestis as well as uncovering the genes in Y. pestis that are responsible for soil survival. Our data will aid the implementation of surveillance strategies, and identification of the environmental signposts that can predict plague outbreaks, both in Madagascar, and by inference in other plague endemic parts of the world, as well as providing information about plague persistence, spread and therefore potential control measures either before or following a resurgent outbreak.",,2022,N/A,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2021 +P21332,NE/W003449/2,Soil survival and re-emergence: the continued threat of plague,"Yersinia pestis (Y. pestis) the bacterium responsible for plague, is probably the most devastating infectious diseases known to humanity and may be responsible for more human deaths than any other micro-organism in history (e.g. during the Black Death). Its 'success' is attributed to the fact that it is extremely contagious, and when untreated, death normally occurs in 1-2 days from bubonic, pneumonic or septicaemic plague. Rodents, fleas and person to person pneumonic transmission are generally considered as fundamental to its rapid spread and although elegant, several facts are inconsistent with this hugely oversimplified model. For example, it is clear that plague can vanish from an epidemic area, only to undergo a resurgence, months or often decades after the original outbreak ceased. Where plague resides during these periods of absence from host and vector populations, and what causes it to re-emerge, has not been studied in detail. Some Y. pestis strains have now acquired multi-antibiotic resistance and an upsurge in transmission of these strains would pose a severe risk to human health, so we need to understand the conditions that might cause a significant re-emergence event to occur. Y. pestis evolved from a near identical, free-living soil-borne ancestor, Yersinia pseudotuberculosis, and soil is therefore thought to be a reservoir for Y. pestis, but how it survives in, and then spreads from this environment has not been adequately investigated. Y. pestis may be protected during this soil stage of its life cycle by embedding in a self-derived protective 'slime' layer (biofilm) enabling the bacterial cells to form a protected association with other bacteria, amoebae or nematodes in the soil. In this study we focus on soil as the important environmental reservoir in which Y. pestis adopts a 'sit and wait' survival lifestyle from where it can re-enter the rodent/human population when conditions are favorable. We aim to identify the environmental and biological triggers that underpin plague survival in, and re-emergence from, soil. To do this we need to take a wide view of the soil environment including factors such as microclimate, soil type, and land cover in association with testing the impact of nematode worms and amoebae on plague survival. Our work will plug a significant and potentially dangerous gap in our understanding of plague ecology, especially important given that the World Health Organization has recently classified Y. pestis as a re-emerging zoonotic pathogen. Using Madagascar as our case study, due to its well recorded plague outbreak history, we will address this knowledge gap using a wide range of scientific approaches. We will use computer based modeling techniques to enable us to predict how plague remains silent for long periods before re-emerging as a new disease outbreak. The model inputs will be obtained by measuring rodent burrow temperatures, humidity and local climate conditions in Madagascar, in conjunction with climate, land cover and soil-type datasets. The models will also use data from Y. pestis soil survival experiments which we will obtain under controlled laboratory conditions. We will also use genetic sequencing techniques to investigate the bacterial soil populations that co-habit with Y. pestis as well as uncovering the genes in Y. pestis that are responsible for soil survival. Our data will aid the implementation of surveillance strategies, and identification of the environmental signposts that can predict plague outbreaks, both in Madagascar, and by inference in other plague endemic parts of the world, as well as providing information about plague persistence, spread and therefore potential control measures either before or following a resurgent outbreak.",,2025,N/A,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2022 +P21333,NE/W00321X/1,Soil survival and re-emergence: the continued threat of plague,"Yersinia pestis (Y. pestis) the bacterium responsible for plague, is probably the most devastating infectious diseases known to humanity and may be responsible for more human deaths than any other micro-organism in history (e.g. during the Black Death). Its 'success' is attributed to the fact that it is extremely contagious, and when untreated, death normally occurs in 1-2 days from bubonic, pneumonic or septicaemic plague. Rodents, fleas and person to person pneumonic transmission are generally considered as fundamental to its rapid spread and although elegant, several facts are inconsistent with this hugely oversimplified model. For example, it is clear that plague can vanish from an epidemic area, only to undergo a resurgence, months or often decades after the original outbreak ceased. Where plague resides during these periods of absence from host and vector populations, and what causes it to re-emerge, has not been studied in detail. Some Y. pestis strains have now acquired multi-antibiotic resistance and an upsurge in transmission of these strains would pose a severe risk to human health, so we need to understand the conditions that might cause a significant re-emergence event to occur. Y. pestis evolved from a near identical, free-living soil-borne ancestor, Yersinia pseudotuberculosis, and soil is therefore thought to be a reservoir for Y. pestis, but how it survives in, and then spreads from this environment has not been adequately investigated. Y. pestis may be protected during this soil stage of its life cycle by embedding in a self-derived protective 'slime' layer (biofilm) enabling the bacterial cells to form a protected association with other bacteria, amoebae or nematodes in the soil. In this study we focus on soil as the important environmental reservoir in which Y. pestis adopts a 'sit and wait' survival lifestyle from where it can re-enter the rodent/human population when conditions are favorable. We aim to identify the environmental and biological triggers that underpin plague survival in, and re-emergence from, soil. To do this we need to take a wide view of the soil environment including factors such as microclimate, soil type, and land cover in association with testing the impact of nematode worms and amoebae on plague survival. Our work will plug a significant and potentially dangerous gap in our understanding of plague ecology, especially important given that the World Health Organization has recently classified Y. pestis as a re-emerging zoonotic pathogen. Using Madagascar as our case study, due to its well recorded plague outbreak history, we will address this knowledge gap using a wide range of scientific approaches. We will use computer based modeling techniques to enable us to predict how plague remains silent for long periods before re-emerging as a new disease outbreak. The model inputs will be obtained by measuring rodent burrow temperatures, humidity and local climate conditions in Madagascar, in conjunction with climate, land cover and soil-type datasets. The models will also use data from Y. pestis soil survival experiments which we will obtain under controlled laboratory conditions. We will also use genetic sequencing techniques to investigate the bacterial soil populations that co-habit with Y. pestis as well as uncovering the genes in Y. pestis that are responsible for soil survival. Our data will aid the implementation of surveillance strategies, and identification of the environmental signposts that can predict plague outbreaks, both in Madagascar, and by inference in other plague endemic parts of the world, as well as providing information about plague persistence, spread and therefore potential control measures either before or following a resurgent outbreak.",,2025,N/A,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2021 +P21334,2746469,"Soil survival and re-emergence, the continued threat of plague","Hypothesis, Rationale and Significance. As the causative agent of plague, Yersinia pestis occupies a prominent place in human history as one of the most destructive infectious human diseases. Fleas and rats have been associated with the spread of the disease with research dating back as far as 1914 ensuring that this model of transmission has become scientific dogma. The general acceptance being that within an inveterate rodent population, enzootic plague episodes ensure Y. pestis is passed through a partially resistant host population by fleas and upon transmission into epizootic hosts plague rapidly spreads. Y. pestis is therefore circulating in associated hosts prior to re-emergence in the human population. Although the elegance of this model of transmission has endured, it is hugely oversimplified. For example, in locations where there have been no human cases or mass rodent die-offs, plague often re-emerges decades after an outbreak such as in Algeria, Libya, Madagascar and India 57, 25, 60 and 30 years later respectively. Given that Y. pestis evolved from a near identical (approx. 98% DNA identity) free-living soil borne gastrointestinal pathogen ancestor, Yersinia pseudotuberculosis, it is highly likely that apparently random plague resurgence events are actually due to the bacteria surviving under highly diverse ecological conditions by adopting a 'sit and wait' lifestyle in soil. However, soil samples used for laboratory Y. pestis survival experiments are almost always sterilized and such experiments generally assume that Y. pestis would survive independently and overlook survival strategies such as biofilm formation in soils or in association with other bacteria, fungi, protozoa or nematodes. It is already known that Y. pestis is resistant to trophozoite predation and can survive and replicate intracellularly in Dictyostelium discoideum and Acanthamoeba castellani and both Y. pestis and Y. pseudotuberculosis can also colonise the soil-dwelling nematode worm Caenorhabditis elegans, which has been exploited as an infection model for biotic surface biofilm formation. Objectives. Fundamental biological questions underlying the biology and molecular mechanisms controlling the soil-dwelling Y. pestis lifestyle have not been investigated and as a WHO classified re-emerging pathogen which is still endemic in some parts of the world, this significant gap in our understanding of plague biology is of grave concern. This PhD project therefore aims to conduct an in-depth study to understand how the soil environment, and associated amoebae and nematodes act as significant reservoirs for Y. pestis during inter-epizootic episodes by addressing the following research questions. 1. How do soil environments impact on Y. pestis survival? 2. Does the presence of nematodes and amoeba enhance Y. pestis survival in soil? 3. What are the key genes and molecular mechanisms involved in Y. pestis survival in soil? These questions will be addressed using a variety of approaches including biofilm persistence assays in soils, amoebae and nematodes infection assays along with genomic and transcriptomic studies, transposon insertion sequencing technologies and targeted gene mutations. The project will be suitable for a student who has a keen interest in molecular genetics and infectious disease and is happy to train to work under containment level 3 conditions. Recent substantial NERC funding through to 2026 means that the student will embed into a team working on complementary aspects of this project and will therefore be fully supported throughout.",,2026,N/A,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2022 +P21336,2720795,The Impact of Plague Outbreaks on Local Courts in England and Wales in the Later Fourteenth Century.,"This research focuses on the impact of pandemics, in this case the Black Death (Bubonic Plague), and the resulting severe depopulation, on pre-industrial institutions, particularly manorial and borough courts, in England and Wales. It explores the intersection between legal, social and economic histories within the context of contemporary concerns over the effect of pandemics upon institutions in the modern world. The Black Death struck England in 1348, swept away between a third and a half of England's population, and epidemics continued to strike throughout Britain for the remainder of the fourteenth century and beyond. This research analyses the quantitative and qualitative evidence of records from local courts. These court records chart the economic activities of the generally non-elite inhabitants of these communities. The project studies the social and economic impacts of the Black Death pandemic. Local courts resolved disputes relating to debt, broken agreements and trespass, and through examining these disputes, the project considers the wider impact of plague outbreaks on commerce and local economies. Although the impact of plague outbreaks on English law has interested scholars for over a century, this has largely focussed on the new labour laws and on impacts to royal courts. The impact of fourteenth century plague outbreaks on local courts has seldom been addressed, and those studies that have addressed this are limited to a single court or a small sample of courts. This is the first work to systematically address the impact of plague on local courts from across medieval Britain.",,2026,N/A,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2022 +P21337,EP/X03058X/1,"Rats and the Archaeology of Trade, Urbanism and Disease in past European Societies","The black and brown rat are among the most globally successful commensal species, and the most significant for European history. Each has spread far beyond its native range in Asia by colonising niches around human settlements, likely reaching Europe in the Iron Age and 18th C respectively. The resulting association with shifting patterns of settlements and trade makes rats potentially valuable proxies for human history-if this anthrodependency can be understood. At the same time, rats have profound impacts on human societies as food pests and agents of disease, most notoriously-if controversially-implicated in historic plague pandemics including the 14th C Black Death. RATTUS aims to chart the history of rats in Europe from late prehistoric origins to the 19th C. While fundamentally archaeological, the project also draws on genetics, textual sources, and ecological modelling to move beyond documentation of dispersal history and build an understanding of underlying processes. How has human history shaped the distribution and ecology of rats over the past 2500 years? What in turn can rat remains tell us about key debates in human history, such as the post-Roman reconfiguration of economic and settlement systems and the emergence of medieval towns and trade? And what roles can rats really have played in the First and Second Plague Pandemics? Despite a recent revolution in plague history bringing unprecedented detail on the evolution and geographic spread of the bacterium itself, knowledge of the rodent populations most widely blamed for its transmission remains superficial, holding back understanding. Addressing these issues in detail has only recently become feasible thanks to advances in bioarchaeological methods: a single rat bone can now reveal taxonomic ID, genetic affinity, disease, diet, and date. The time is thus ripe for a systematic effort to unlock the potential of these most fascinating and significant of rodents as a source for-and factor in-human history",,2027,N/A,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P21340,2441001,Developing effective rat control for rural Madagascar landscapes: using individual based modelling to inform strategies,"Across the developing world, food insecurity is greatest in rural areas, where smallholder farms predominate. Increased productivity of such farms has important positive effects on livelihoods and is essential for the global fight against hunger. The development of effective management strategies to reduce crop losses from agricultural pests requires an understanding of how pest populations will respond to control, at both the population and agricultural landscape scale. Rodent pests contribute significantly to food insecurity. Globally, rodents annually eat and spoil cereals that could feed ~280 million people in developing countries alone. They are also important reservoirs for a range of livestock and human diseases. In some countries in Asia and Africa, increased understanding of processes contributing to variation in rodent abundance has led to the successful development of Ecologically Based Rodent Management (EBRM). EBRM targeting community actions at key times of year in specific locations can significantly reduce losses. Although traditionally most actions aim to reduce pest survival (e.g. trap barrier systems), there is increasing interest in contraceptive baits. In Madagascar, undernourishment remains a prevalent problem. Smallholders predominate and rice is the staple food. The black rat, the major rodent pest, is found in all habitats from forest to cultivated areas and villages. Moreover, this species is a reservoir for diseases that can be transmitted to humans and/or livestock (e.g. plague, leptospirosis). EBRM is not presently practiced in Madagascar and there is an opportunity to develop strategies that improve both food security and human and livestock health. Previous studies provide a good base knowledge of the population ecology of the black rat, as well as the epidemiology of several rodent associated diseases. However, there is an urgent need to predict landscape-level responses of populations and diseases to alternative control strategies. For example, removal of individuals through trapping or poisoning may favour increased dispersal of animals from non-control areas, possibly completely negating any benefits from control and also contributing to disease spread. This interdisciplinary project will use existing rodent trapping data and a systems modelling approach to explore management options. Using a recently developed individual-based modelling platform, RangeShifter, which integrates population dynamics, dispersal behaviour and genetics, and can be used to simulate scenarios on spatially explicit landscapes, this project will (1) compare the effectiveness of targeting rat control in different habitats and different seasons, using a model parameterised with existing trapping data and landcover maps, (2) incorporate individual disease status into RangeShifter and investigate the impact of control on the landscape epidemiology of different pathogens, including plague and leptospirosis and (3) test model predictions against field data from control trials.",,2024,N/A,,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector control strategies | Impact/ effectiveness of control measures,2020 +P21349,2750749,Polymersomes to enhance therapeutic options for treating intracellular bacterial infections,"The risk of exposure to an infectious agent for military personnel can be high as a consequence of exposure to endemic diseases in deployment environments, as a consequence of battlefield injuries or due to exposure to a deliberate release of a biological warfare (BW) agent. A common feature of many bacterial BW agents is that they are intracellular pathogens with low infectious dose and high mortality rates. Examples include Burkholderia pseudomallei, the causative agent of melioidosis, Francisella tularensis, the causative agent of tularaemia, Yersinia pestis, the causative agent of plague and Coxiella burnetii, the causative agent of Q fever. Infections caused by these are inherently difficult to treat and current therapeutic options are limited and often inefficient.[1, 2, 3] Furthermore, the ever growing misuse and overuse of antibiotics had led to the accelerating emergence of multi-drug resistant bacteria and failure of existing therapeutics.[4] Consequently, there is an immediate medical need for the development of new effective treatments [5] which can be easily deployed and administered in a military setting. The aim of this project will be to investigate novel PM-based encapsulation technology to enhance bioavailability of existing therapeutics for the treatment of BW infections. Since reducing the logistical burden of antibiotic delivery is essential in a military operational context, a research focus will be the investigation and development of formulations that can be self-administered, for example by oral or inhalational routes. The project activities of this part-time PhD will be largely conducted at Dstl. The project will capitalise on access to existing PM formulation expertise at the University of Southampton and the facilities at Dstl which will allow in vitro and in vivo work to be conducted using containment level 3 (CL3) BW pathogens.",,2028,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2021 +P21372,2885033,Optimising invasive species control to reduce zoonotic disease risk and agricultural losses in Madagascar,"Invasive alien species (IAS) cost a global minimum of US$46 billion annually, including huge agricultural losses and damage to human health and wellbeing. Tackling the socioeconomic impacts of IAS thus has key significance for addressing global susceptibility to disease and hunger. However, developing effective strategies against established IAS requires significantly improving our current knowledge-base and management toolkit. In Madagascar, the Asian toad Duttaphrynus melanostictus is spreading following an accidental introduction in the east of the island over a decade ago, with multiple socioeconomic and health consequences. As a toxic species, it poisons higher predators like snakes, eliminating predatory constraints on rodent populations (e.g. the black rat Rattus rattus), that are both agricultural pests and reservoirs for zoonotic diseases including plague and leptospirosis. As a predator, D. melanostictus can reduce beneficial crop-pest predator populations and eliminate farmers' additional income generation (e.g. honey production), reducing food availability, household resources and economic empowerment. This invasive species therefore represents an increasingly significant threat, and this project provides an opportunity to advance our ability to improve food security and human health, making progress towards UN sustainable development goals. Currently direct and indirect interactions between toad and rodent populations and their consequences for socioeconomic and health outcomes are poorly understood. This interdisciplinary project will work in collaboration with the Madagascar Fauna and Flora Group (a local NGO), government and local stakeholders to address these knowledge gaps at a landscape scale. It will combine existing data on toad and rodent distributions and control methodologies in Madagascar, with the potential for new field data collection and individual-based and epidemiological modelling to optimise approaches across the invasion gradient. Key research aspects include: a) Developing a targeted model of density-driven interactions between toads, rats and apex predator populations to understand the agricultural and epidemiological consequences across the invaded range b) Investigating the efficacy of control methodologies and strategic options to slow/halt the invasion front and improve detection and response strategies c) Testing model predictions against field data d) Assessing the diet of toads across the invasion gradient to determine variation in socioeconomic impacts",,2027,N/A,,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae | Unspecified,,,,,,,,,Plague | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P21394,10080057,"Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses","Project summary Researchers worldwide have been working to develop a universal flu vaccine, but no breakthrough has yet been achieved. FLUniversal is not ""another costly universal flu project"". It is an opportunity to create a genuine universal flu vaccine that will set the standard for rapid, efficient vaccine development, and generate know-how and tools to develop next-generation vaccines. We plan to exploit our increased understanding of molecular mechanisms of influenza infection and immunity to develop a vaccine effective against all flu virus strains. Our innovation uses genetically modified flu strains administered intranasally in a prime-boost regimen. This approach rapidly induces interferon and broadly cross-neutralising antibodies in the nasal passages and a systemic immune response directed to the conserved HA stalk. Proof of concept for universal protection was demonstrated in the ferret; we propose now to show proof of concept in humans. Previous clinical studies established safety and immunogenicity in humans. The strains are efficiently produced in Vero cells. FLUniversal's objectives align with the Expected Outcomes: comprehensive immunological assessment of preclinical models, development of a human challenge model, and assisting healthcare stakeholders’ decision-making about support for vaccine development. Consortium members’ world-leading expertise in preclinical models, clinical trials, immunology and validated assays will provide valuable insights on mechanisms of protection. Proposed clinical studies will provide crucial clinical proof of concept to advance the vaccine toward commercialisation.",,2027,"Innovate UK, Medicines and Healthcare products Regulatory Agency",423495,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Innovation,,,United Kingdom | United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Pre-clinical studies,2023 +P21395,AH/V006924/1,Assessing the viability of access and benefit-sharing models of equitable distribution of vaccines in international law,"Developing and distributing a COVID-19 vaccine is key to the global response strategy. How a resulting vaccine will, and ought to, be distributed is a vital question; encompassing fairness, equity, and justice for developing countries, who are likely to have poor access to a COVID-19 vaccine without some form of framework guiding allocation at the international level. It is likely that any such framework will be developed through the World Health Assembly, and there are already calls for the WHO to develop such a framework to guide the distribution of any resulting vaccine. Within international law there exist two international legal agreements upon which to model a COVID-19 distribution framework: the WHO Pandemic Influenza Preparedness Framework, and the UN Nagoya Protocol to the CBD. These agreements take significantly different approaches to equitable distribution and the operationalisation of the distribution. This project will assess these international agreements suitability for providing a model for COVID-19 vaccine distribution. This project uses doctrinal legal analysis and legal epidemiology to assess the extent to which these international agreements can provide a legally robust framework on which to model an agreement to ensure ethical distribution of a COVID-19 vaccine upon. From this the project will provide 'lessons learned' from the analysis of the WHO Pandemic Influenza Preparedness Framework, and the UN Nagoya Protocol to the CBD, to inform the development of a COVID-19 vaccine distribution through the World Health Assembly.",,2021,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Vaccines research, development and implementation | Research to inform ethical issues",Vaccine logistics and supply chains and distribution strategies | Research to inform ethical issues in the Allocation of Resources,2020 +P21397,2765298,Optimising genomic RNA RNA interactions for development of flexible influenza virus vector backbones for co vaccination,"The Live Attenuated Influenza Vaccine (LAIV), marketed as FluMist/Fluenz by AstraZeneca forms the backbone of the United Kingdom's childhood influenza vaccination programme and is given as a nasal spray annually to all 2-12 year-olds. Unlike inactivated vaccines, LAIVs are unique in generating significant mucosal immunity (Barria et al., J Infect Dis, 2013), offering the possibility of pre-empting virus spread from the upper to lower respiratory tract and consequent risk of severe disease. In the 2013-14 and 2015-16 influenza seasons, low vaccine effectiveness was observed for the H1N1 component of FluMist in the USA, attributed to decreased LAIV replication in human nasal epithelial cells (Hawksworth et al., Vaccine, 2020), rather than decreased HA antigen stability (Parker et al., Vaccine 2019). One potential contributing factor to this reduced fitness was a decrease in the production of infectious virus particles carrying all eight genome segments. Observations also suggest that the ability of the historic MDV genome to incorporate HA and NA genes from different, contemporary influenza A viruses can vary, resulting in LAIV strains with unexpected replicative differences. This project aims to understand how the genome segments of LAIVs are assembled in order to bioengineer a next-generation of LAIVs suitable as flexible vectors for all seasonal or pandemic influenza strains and co-vaccination against viruses such as SARS-CoV-2 - to which we have no vaccine that confers mucosal immunity. Such a vaccine would be invaluable, since existing vaccines are largely ineffective at halting transmission. This project aims to (1) map RNA:RNA interactions that drive assembly of LAIV strains and (2) to use this knowledge to engineer a flexible MDV backbone enabling efficient generation of either seasonal or pandemic LAIV, that (3) can also act as a flexible platform for co-vaccination of influenza along with other respiratory pathogens.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity",2021 +P21399,MR/X008312/1,"Transcription, replication, trafficking and assembly of the influenza virus RNA genome","Influenza viruses are important human and animal pathogens that have the potential to cause severe respiratory disease and death in humans. Influenza A and B viruses are responsible for seasonal epidemics and influenza A viruses also have the potential to cause pandemics. Influenza A viruses infect a wide range of animal species, with wild waterfowl being considered their natural reservoir. All four influenza A virus pandemics of recent human history occurred when either an avian influenza virus transmitted directly into the human population, giving rise to the 1918 pandemic, or avian or swine influenza viruses combined with human seasonal influenza virus, leading to the 1957, 1968 and 2009 pandemics. In the case of a new emerging influenza pandemic virus, no vaccines would be available initially and antivirals would be crucial to tackle the first wave of the virus; however, currently available influenza antivirals are limited. The focus of our research programme is the RNA polymerase of influenza viruses, a large multifunctional enzyme complex. The function of the influenza virus RNA polymerase is to make copies of the genetic information of the virus, stored in segments of RNA. After an influenza virus infects a cell, the RNA polymerase first makes copies of the genetic material, which the cell is then 'forced' to read to make viral proteins, building blocks of new virus particles. The RNA polymerase also makes copies of the genetic material to be packed into new viruses and recent research suggests that it even plays a role in transporting the new genetic material to the sites in the cells where new virus particles are assembled. The RNA polymerase of influenza viruses is considered a prime viral target for the development of novel antiviral drugs; without it the virus is unable to make new copies of itself and spread to infect further hosts. Indeed, several polymerase inhibitors have been developed recently which are licensed for use in emergency in a limited number of countries. However, development of resistance against these antivirals has already been documented. Our research programme aims to understand exactly how the influenza virus RNA polymerase reprogrammes the cell to make viral proteins and produce new copies of the genetic material to be packed into new virus particles. To perform these functions the virus hijacks host proteins that act together with the viral RNA polymerase. We aim to understand how the viral RNA polymerase interacts with these host proteins, how these host proteins assist the RNA polymerase in promoting the copying of the viral genetic material, and where these interactions occur in the host cell. We also aim to elucidate the role of the viral RNA polymerase in transporting the copied genetic material to the sites of virus assembly inside the host cell. Addressing these objectives will result in new knowledge about the fundamental biology of influenza virus infections. As such, it will also help with the assessment of the pandemic potential of emerging influenza virus strains and therefore has potential to inform public health policies. Importantly, results from this programme will underpin further work into targeting the viral RNA polymerase for antiviral development and could contribute to the development of improved or entirely novel influenza vaccines. To translate findings from our current and proposed research into antiviral therapies, we already have established links with industrial partners. Furthermore, we actively seek new opportunities with industrial collaborators for translating the knowledge generated.",,2028,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies | Pre-clinical studies",2023 +P21400,BB/V000292/1,How does Musashi 1 enhance Zika virus replication?,"Viruses spread by insects cause some of the most important emerging human diseases. As the range of their insect hosts expands, increasing populations are becoming at risk to infection. An outbreak of Zika virus, spread by mosquitos, in Central and South America in 2015/2016 was accompanied by an increase in microcephaly cases in new-born babies. Microcephaly is a condition where the head circumference is smaller than usual and is typically associated with developmental defects. A causal link between Zika virus infection and defects in neural cell and brain development has since been firmly established with neural stem cells being particularly susceptible to infection, and destruction, by the virus. Recent evidence has also demonstrated a link between Zika virus infection and long-term cognitive dysfunction, suggesting that both adults and foetuses are at risk of debilitating disease following exposure. Like other viruses, Zika virus can only replicate once it enters a host cell. The virus genome consists of a single piece of nucleic acid called RNA that is replicated and packaged into new virus particles before being released to spread the infection. Virus replication can be positively and negatively affected by proteins present in the infected cell. Many of these are RNA-binding proteins that interact directly with the viral genome. We recently demonstrated that a host protein called Musashi-1 strongly enhances Zika virus replication. Musashi-1 is known to affect the expression of specific proteins by binding directly to their corresponding RNAs. High levels of Musashi-1 are present in the neural precursor cells that are highly susceptible to Zika virus infection. A mutation in Musashi-1 that affects its ability to interact with RNA is also linked to congenital microcephaly, independent of Zika virus infection. Together, our previous findings support the hypothesis that the presence of Musashi-1 in Zika virus infected cells may contribute to the neural destruction and associated brain development defects observed in affected individuals. In this project we will examine the interplay between Musashi-1 and Zika virus using cutting-edge techniques. We will focus on three main questions: 1) At what stage of the Zika virus replication cycle does Musashi-1 exert its effect and can mutation of Musashi-1 binding sites in the Zika virus RNA affect its ability to reproduce in neuronal cells? 2) Does sequestration of Musashi-1 through binding to the Zika virus RNA disrupt the normal function of Musashi-1 in neuronal cell development? 3) Does Musashi-1 promote the ability of Zika virus to replicate in neural stem cells in mini brains? From this work we expect to advance our knowledge of how the presence of a protein that normally promotes neural cell development can make cells more permissive for Zika virus replication. This research can also reveal novel aspects of basic neurodevelopmental processes. Understanding how Musashi-1 enhances Zika virus replication may ultimately help us to develop safer vaccines with reduced risk of damaging side effects.",,2021,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P21401,BB/V000292/2,How does Musashi 1 enhance Zika virus replication?,"Viruses spread by insects cause some of the most important emerging human diseases. As the range of their insect hosts expands, increasing populations are becoming at risk to infection. An outbreak of Zika virus, spread by mosquitos, in Central and South America in 2015/2016 was accompanied by an increase in microcephaly cases in new-born babies. Microcephaly is a condition where the head circumference is smaller than usual and is typically associated with developmental defects. A causal link between Zika virus infection and defects in neural cell and brain development has since been firmly established with neural stem cells being particularly susceptible to infection, and destruction, by the virus. Recent evidence has also demonstrated a link between Zika virus infection and long-term cognitive dysfunction, suggesting that both adults and foetuses are at risk of debilitating disease following exposure. Like other viruses, Zika virus can only replicate once it enters a host cell. The virus genome consists of a single piece of nucleic acid called RNA that is replicated and packaged into new virus particles before being released to spread the infection. Virus replication can be positively and negatively affected by proteins present in the infected cell. Many of these are RNA-binding proteins that interact directly with the viral genome. We recently demonstrated that a host protein called Musashi-1 strongly enhances Zika virus replication. Musashi-1 is known to affect the expression of specific proteins by binding directly to their corresponding RNAs. High levels of Musashi-1 are present in the neural precursor cells that are highly susceptible to Zika virus infection. A mutation in Musashi-1 that affects its ability to interact with RNA is also linked to congenital microcephaly, independent of Zika virus infection. Together, our previous findings support the hypothesis that the presence of Musashi-1 in Zika virus infected cells may contribute to the neural destruction and associated brain development defects observed in affected individuals. In this project we will examine the interplay between Musashi-1 and Zika virus using cutting-edge techniques. We will focus on three main questions: 1) At what stage of the Zika virus replication cycle does Musashi-1 exert its effect and can mutation of Musashi-1 binding sites in the Zika virus RNA affect its ability to reproduce in neuronal cells? 2) Does sequestration of Musashi-1 through binding to the Zika virus RNA disrupt the normal function of Musashi-1 in neuronal cell development? 3) Does Musashi-1 promote the ability of Zika virus to replicate in neural stem cells in mini brains? From this work we expect to advance our knowledge of how the presence of a protein that normally promotes neural cell development can make cells more permissive for Zika virus replication. This research can also reveal novel aspects of basic neurodevelopmental processes. Understanding how Musashi-1 enhances Zika virus replication may ultimately help us to develop safer vaccines with reduced risk of damaging side effects.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P21402,10026208,A Single-dose DNA vaccine platform to safely induce protective immunity against Zika,"Our team has already developed a fast, low cost and effective DNA vaccine that stimulates potent immune responses for COVID-19 and its variants in mice. This has entered human trials aiming to demonstrate safe and effective vaccination and immune booster deployment. This approach can also be used to develop a safe and effective vaccine to prevent infection by flaviviruses such Dengue and Zika. Like other Zika vaccines being developed, ours will help the body to make antibodies to stop the Zika virus entering cells and causing the person to become infected. What makes this vaccine different from other approaches is that it will also stimulate the immune system to make special T cells that can recognise and kill cells that may have been infected with the virus. These T cells will also remain in the body longer than antibodies and be there in case of future infections. The proposed Zika vaccine will be generated as several variants targeting either a non-structural protein made by the virus, or a defective intact virus using DNA as the template. Most DNA vaccines under trial are administered using mild electric shock (electroporation) or pressure to increase efficacy of the DNA delivered. Although this approach works it requires an expensive device to deliver the vaccine. This is not practical when millions of healthy subjects will need to be immunised, as during the COVID-19 pandemic, or in potential future pandemics of flaviviruses like Zika. To overcome this problem, we have developed an elegant system to allow the DNA to be given by simple injection. This technology is called GET and we have modified this system to enhance the activity of vaccination for COVID-19 using polymer chemistry. Our aim is to test the new Zika vaccines we engineer by vaccinating mice and at the end of the project be positioned to allow us and our Brazilian collaborators to start human trials quickly and validate our novel DNA approach in Brazil, a country significantly affected by Zika. This strategy could have a transformative impact on pandemic prevention in the developing world and globally. Importantly this will allow a new class of DNA vaccines to be employed for many other diseases allowing us to be better prepared for the next pandemic.",,2023,"UNIVERSITY OF NOTTINGHAM, INNOVATE UK",605825.22,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Innovation,,,United Kingdom,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P21403,2612986,Advancing our understanding of the determinant of symptoms Zika virus infection,Pending,,2026,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,,,2021 +P21404,2415856,"Bodies, borders and bugs: the construction and destruction of Zika threat in the UK, US and WHO","The research will examine the complex geographies of threat, difference and fear that arise as powerful geopolitical actors seek to contain the spread of disease. The research probes what can be learnt from the spread of the Zika virus, in particular the epidemic in the Americas since 2015. Multiple institutions across the globe - both state and non-state -- sought to generate knowledge concerning the spread and science of Zika, reflecting a wider geopolitical landscape of authority and expertise. In this way the virus was geo-graphed: written on and through certain places and represented in spatial terms. This research examines the production of knowledge concerning Zika, initially through discourse analysis of public health policy (MPhil in Geographical Research). I will explore the central themes of embodiment, immigration, (ab)normality and health security as the discourse negotiates the variety of actants, boundaries and spaces that are entangled in this particular 'outbreak narrative': the nation state and international state system; the human body; the mosquito; and the pathogen itself. This dissertation will also study the elicitation of expertise as these actants are discussed.",,2024,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P21405,NE/T014687/1,Exploring Risk Factors for Sequential and Concurrent Dengue and Zika Outbreaks in a Naïve Population,"Flaviviruses pose an ever increasing problem for the worldwide population. Before 1970 only 9 countries had experienced severe dengue epidemics; now dengue is endemic in over 100 countries. Similarly, before the 1980s human infection from Zika was a very rare occurrence; now 86 countries have reported mosquito-transmitted Zika outbreaks. It is challenging to predict which flaviviruses will result in the next epidemic and the dynamics between co-circulating pathogens may be responsible for increased morbidity. Antibody dependent enhancement (ADE) is known to increase the severity of dengue-related illnesses when a population is infected with different serotypes of dengue consecutively. It is believed that this mechanism may also occur between dengue and Zika owing to their near identical structures, which is particularly concerning as they share the same vectors, Aedes aegypti and A. albopictus. As a result of climate change, the habitat of these mosquitoes is expanding and in recent years persistent populations of A. albopictus have been found as far north as Southern Ontario in Canada with A. aegypti being found in previous years. Currently, there is no approved vaccine for dengue or Zika. For dengue this is in part due to the effects of ADE, which could see vaccinated individuals with no prior exposure experiencing severe side effects should they be subsequently infected. Therefore, the dynamics within dengue serotypes and between them and Zika is crucially important for any future prevention and control policies. This project aims to elucidate the dynamics of co-circulating flaviviruses considering ADE through the use of statistical and mechanistic models. By integrating the statistical models used currently by the Public Health Care Agency of Canada (PHAC) to represent the distribution of Aedes across Canada with a mechanistic model for dengue and Zika considering ADE, we will be able to forecast the change in risk for sequential and concurrent dengue and Zika outbreaks that take into account the effect of climate change.This project will determine the number of imported cases and vectors carrying dengue and/or Zika required for sequential and concurrent outbreaks to occur and which environmental and demographic variables have the biggest impact upon future invasion risk. Modelling infectious diseases requires an interdisciplinary approach and this project will take full advantage of the wide variety of specialists accessible through Dr Greer and her lab group. Her monthly lab group meetings are attended by individuals from PHAC which facilitates an exchange of ideas and expertise between academics and policy makers. There will be opportunities to collaborate with other academics such as Dr Heffernan who specialises in co-infection, from York University, and Dr Rob Deardon, a biostatistician at the University of Calgary. Furthermore Entomogen Inc., a company which monitors the mosquito population and carries out viral testing, is based in Ontario. Visits to this group will improve understanding of how mosquito data are gathered and elucidate any possible biases in reported data. Finally, in 2020 the American Society for Tropical Medicine and Hygiene are holding their annual conference in Toronto, which will provide an ideal opportunity to network with experts in the flavivirus research. At the conclusion of this project we will have developed a model that can be utilised to establish the risk of outbreaks of dengue fever and Zika occurring in Canada that takes into account future climate change. The outputs of this model will be communicated directly to our collaborators at the University of Guelph and PHAC, thus informing contingency planning for outbreaks of flaviviruses in Canada in the future.",,2022,N/A,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2020 +P21406,2393578,"How the Zika virus outbreaks in Colombia, and subsequent public health responses, have influenced constructions of identity and power for the people a","Research question and aims I will take a decolonial, intersectional approach to explore how the Zika virus outbreaks in Colombia, and subsequent public health responses, have influenced constructions of identity and power for the people affected, investigating how gender, race, class and disability are constructed. The outbreaks have caused explosions of biomedical research but the social consequences have received less attention. This work will build on existing literature concerning the implications of Zika for universal health coverage; human rights; and health inequities, drawing on insights from reproductive justice to help resolve some of the tensions therein (Kuper, Smythe, and Duttine, 2018; Mohapatra, 2019; Rivera-Amarillo and Camargo, 2019). This research will influence public health policy on infectious disease, ensuring that the consequences of such policies for oppressed and marginalised groups receive due consideration, and shifting the focus towards the social implications. This will contribute to IGH's goal of producing high quality research that can be translated into practical solutions that promote better health for the most vulnerable in society.",,2023,N/A,,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Sexual and gender minorities | Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Gender,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts,2020 +P21407,10026776,Phase 1b/2 study of a Modified Vaccinia Ankara vectored Zika Vaccine to assess safety in previously flavivirus exposed healthy adults.,"Zika virus is a common mosquito spread viral infection that usually causes mild fever but in pregnant women may damage the unborn baby and cause major disability. Children are born with small heads and suffer intellectual and physical impairment. This has been a particular problem in south and central America in recent years but zika infection is also present in many countries in tropical regions. No treatment for zika virus infection is available thus prevention by vaccination is desirable. However any vaccine should be safe to use in young and pregnant women to safeguard the mother and child from harm. We have designed and produced a zika vaccine by incorporating bits of the zika virus genetic code in a smallpox vaccine. The smallpox vaccine has been chosen as it has been used to make other vaccines previously, it has a strong track record of safety and this particular vaccine cannot make copies of itself when injected in a human and therefore should to be safe when used in pregnancy. MVA is not owned by anyone, therefore the vaccine manufacture should prove relatively inexpensive and the vaccine made available at a price suitable for low and middle income countries. The bits of the zika vaccine that have been included incorporate several components that allow the immune system to generate multiple immune responses, which we believe will provide a more protective vaccine and work better in areas of the world where zika circulates. Our vaccine is known as MVAZIKAB. It has completed laboratory studies prior to use in humans and to date has been shown to produce a strong immune response that protects against zika infection in mice. It has been manufactured so it is now suitable for use in humans. We will undertake the immunisation of the first healthy volunteers in early 2022\. If as we expect these initial studies prove safe we will extend the study to increase the number of healthy volunteers to get a better understanding of immune response. However and importantly, we will give the vaccine to a small number of healthy volunteers who have been exposed to other infections similar to zika. This will be a common occurrence if we are to use this vaccine in areas of the world where zika circulates and ensuring safety and immune response in this group will provide reassurance for further studies in endemic regions of south America.",,2023,"INNOVATE UK, UNIVERSITY OF LIVERPOOL",638445.53,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,,Innovation,,,United Kingdom,,"Vaccines research, development and implementation",Phase 0 clinical trial | Phase 1 clinical trial,2022 +P21409,2888319,Modelling the Impacts of Climate Change on Mosquito-Borne Diseases,"This project will focus on modelling the population dynamics of the highly invasive mosquito species Aedes albopictus and Aedes aegypti, and their human diseases such as Dengue, Chikungunya and Zika. The modelling approach will be to use systems of environmentally driven stage-structured delayed differential equation models (see References & Further Reading) to predict current and future disease risk at a global scale. The models will be fitted and validated against a broad range of datasets and overlaid with data on human populations, tourism and trade pathways, and disease interventions. The models will be driven by an ensemble of climate change models to predict future risk. Using interactive visualisations, model outputs will be disseminated through key stakeholder and community engagement",,2027,N/A,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2023 +P21410,BB/X002500/1,Synthetic within-cell flavivirus sensors,"The aim of the proposed study is to develop synthetic-biology sensors that can sit in living cells, essentially inert until the cell is infected by a virus, and then activate and respond. For this proposal, we focus on flaviviruses, a major group of viruses that includes mosquito-transmitted viruses dengue, Zika and yellow fever viruses, as well as some viruses transmitted by ticks, for example. When viruses infect a cell, they use a lot of the cell's own machinery for their replication, but they also have some proteins of their own, encoded in their own small genomes, that an uninfected cell does not have. These provide the basis for specific detection - the cell does not have these proteins and enzymes unless it is infected. Unlike the virus' sequence, which is very specific to individual virus types, or even strains of a single virus, these enzymatic activities are quite similar between different viruses of the same general group - e.g. flaviviruses, or mosquito-transmitted flaviviruses, so we expect to develop sensors that will respond to any of a range of viruses, perhaps to all mosquito-transmitted flaviviruses, rather than to just, for example Zika virus, or one strain of Zika virus. Such systems have several potential uses. One is in diagnostics. Sequence-based detection systems, such as PCR, need some prior knowledge of the virus sequence, and are very sensitive to variations in this sequence (i.e. may fail to detect a variant). More comprehensive approaches exist, such as complete sequencing, but these are currently relatively slow and expensive. Another standard approach involves applying the putative virus sample to cultured cells and looking for disruption of those cells (cytopathic effect, CPE), but this is a little slow, and not all viruses cause obvious pathology. We have developed prototype within-cell systems that appear to have superior characteristics, at least for some purposes. We will develop these and characterise them in detail, with project partners, to provide a set of tools complementary to current approaches. We will use the same approach in mosquitoes, to develop mosquitoes that respond in specific ways to infection by Zika virus and other flaviviruses. Our main aim here is for that response to reduce the ability of the mosquito to transmit the virus. Unlike humans, mosquitoes are not severely affected by these viruses, indeed it is important for the virus not to harm the mosquito much since it depends on her (always ""her"": only female mosquitoes bite) for transmission. If we can arrange that infected mosquitoes are unusually sensitive to infection, e.g. are killed by the virus, this will greatly reduce transmission. Such systems would additionally need to be spread into a target mosquito population in the wild. That is not part of this project, which is entirely lab-based, but potentially a future development if this project is successful.",,2026,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P21411,2887691,Harnessing the power of T-cell responses to control future pandemics,"Several virus families are capable of causing sudden outbreaks, and by definition, for newly emerging viruses, vaccines are not available. Unlike antibodies, T-cell responses are often cross-reactive between pathogens. Therefore, choosing conserved regions of viruses as target vaccine antigens offers a strategy for making vaccines that have some efficacy before a virus has emerged. However, before this can be done, these conserved regions must be identified, and evidence for their protective capacity must be provided. This project will focus on two RNA virus families that are medically relevant: flaviviruses and coronaviruses, specifically SARS-CoV-2. Flaviviruses include dengue, Zika, West Nile and others. The project will aim to develop novel approaches to selecting vaccine antigens for diseases relevant to global health, with the ultimate aim of prevention of future outbreaks. Flaviviruses have caused notable outbreaks such as the 2015 Zika epidemic. SARS-CoV-2 continues to cause many infections despite the availability of vaccines and antivirals. Using samples from several local and national studies, including a phase I clinical trial of a Zika vaccine developed by our team, this project will investigate the phenotype of CD8+ T-cells that develop after both natural infection and vaccination. The student will learn techniques in T-cell epitope mapping, several methods for assessing the T-cell functions (primary supervisor), and bioinformatics (secondary supervisor) to identify T-cell epitope conservation between viruses. They will work on published and experimentally determined epitopes. Bioinformatic analyses will examine where these epitopes are found in relation to protein function, and conservation across different viruses within a family. Next, variant epitopes will be synthesised and tested experimentally to examine this relationship between protein function, conservation, and cross-reactivity of the T-cell response. The avidity and function of responses against cross-reactive epitopes will be tested to ensure they are high quality and expected to provide protection. Antigen specific cells will be sorted for single cell RNA-seq using tetramers/pentamers, to address whether receptor usage or transcriptional profile drives cross-reactivity. The student will then use samples from human experimental medicine studies testing heterologous flavivirus exposure, and directly test (for flaviviruses) which eptiopes cross-react between priming and subsequent heterologous infection in humans, using infectious vaccines. There will also be the opportunity to test real-world responses against a vaccine designed in Liverpool to target both SARS-CoV-2 and MERS-CoV. The above work will uncover the underpinning principles of epitope selection. Finally, these epitopes will be tested by synthesising enveloped mRNAs for antigen presentation assays, to ensure that they can be processed, presented and recognised by human T-cells, using antigen expanded short term T-cell cultures (a well-established method in our lab). The student will benefit from a broad range of training in human immunology and bioinformatics, allowing them to develop good interdisciplinary skills. They will also benefit from working on samples from human studies, so they will learn how to work in a laboratory at GCP, and the governance and regulatory aspects of early phase product development. There will be opportunities to learn programming in R, and to apply both these and other newly acquired bioinformatics skills to the processing of immunological data using pipelines under development in the lab of the primary supervisor.",,2027,N/A,,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P21412,2439064,Psoriasis and eczema modulate susceptibility to arbovirus infection,"The climate crisis is making mosquito-borne virus infections an increasing threat to human health. These viruses, such as those that cause Zika and dengue, are infecting more people and spreading to new countries as the climate warms and globalisation helps mosquitoes spread. These viruses are transmitted to people when biting mosquitoes spit virus into the skin. We have shown that inflammation caused by the mosquito bites helps these viruses replicate and spread around the body. We now have important new data that suggests patients with skin inflammatory disorders (psoriasis and eczema) may have different susceptibilities to these infections, and that this may relate to how immune defences are activated in the skin. Psoriasis and eczema are debilitating skin conditions that affect approximately 3% of the global population. Skin from these patients exhibit abnormal expression of cytokines and leukocyte positioning. Patients typically require lifelong treatment with potent immune-modulating drugs (e.g. cytokine-neutralising antibodies). Eczematous skin appears to be more susceptible to arbovirus infection, whilst psoriatic skin is less susceptible to infection. It is not clear why this is the case. Infection of the skin by these viruses represents an essential stage of virus life cycle; robust replication at this site is a pre-requisite for development of clinical disease. Aberrant positioning of the leukocytes in the skin of psoriasis/eczema patients and their ability to differentially secrete cytokines may account for differences in disease predisposition. Objectives: To determine in eczematous/psoriatic skin how; 1. infection with arbovirus differs (e.g. magnitude, kinetics, and cellular tropism of virus) 2. leukocyte composition and positioning within the skin and their ability to activate anti-viral immune responses differs In doing so, this new interdisciplinary project will uniquely combine aspects of dermatology, virology and immunology. It has potential to inform individualised patient care strategies for those at risk of infection; or if infected, help stratify clinical outcome. We also expect that the emerging knowledge from this work, on the role of skin immune responses following arbovirus infection (eczema, psoriasis and healthy skin as exemplars), will open a unique opportunity to develop protective strategies that inhibit arbovirus infection in general. i.e. these studies will help us understand what types of inflammatory responses are key for fighting virus infection. Experimental approach: 1. We will compare ex vivo infection of human skin explants from healthy, psoriasis, eczema and treated patients. We will use Zika virus, an important and representative arbovirus, for which fluorescence expressing strains exist. 2. Inflammatory responses of skin cells will be characterised by transcriptome profiling of FACS isolated cells and validated by qPCR/immunohistochemistry. 3. In vivo experiments that target the most promising immune pathways will be performed using our established model",,2024,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Pathogen: natural history, transmission and diagnostics",Prognostic factors for disease severity | Immunity,2020 +P21413,2750155,Vector in the machine: how accurately can mosquito transmission of viruses be predicted by machine learning?,"Through climate change and human travel, many mosquito-borne viruses are rapidly emerging and having substantial impacts on global health. Zika and West Nile have emerged over the last 2-3 decades, and Usutu virus has emerged across Europe, including incursion into the UK in 2020. For each of these viruses, previously naive mosquito species and populations were the drivers of transmission in new areas. The ability to predict whether a novel mosquito is capable of virus transmission computationally and before incursion will greatly bolster estimation of risk, preparedness, and mitigation of new outbreaks. Our group has developed machine learning frameworks to predict virus/host associations, broadly across all mammals, as well as specifically for coronaviruses. Ongoing work is adapting those pipelines to mosquito-borne viruses, and this project will experimentally validate and refine those machine learning pipelines. This interdisciplinary project will be the first to experimentally validate machine learning-produced mosquito/virus competence predictions, and the first to make refinements based on experimental validation. Using machine learning predictions of competent mosquito/virus combinations, and experimentally validate the pipeline by live virus infection of mosquitoes in the CL3 lab. Colony mosquitoes will be fed on a virus-spiked blood-meals, incubated, and have their saliva extracted. Presence of virus in the saliva (plaque assay or qRT-PCR) demonstrates competence. Using these results, strengths/weaknesses in the machine learning pipeline will be identified i.e. what was it failing to predict? Identifying patterns and refine the pipeline accordingly.",,2026,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,Zika virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P21415,2443636,Visual processing in mosquito larvae,"Background.Malaria is a disease that affects half of the world population and their livestock.Currently the progress in malaria elimination has stalled, partly due to emerging insecticide resistance.New intervention strategies are urgently needed, and targeting larvae is a promising approach that has been briefly explored in the past.Now it is timely to revisit the idea of targeting mosquito larvae incorporating new genetic tools and a deeper understanding of larval behaviour.In addition, mosquito larvae have recently become a new genetically tractable neuroscience model organism, that will help us gain fundamental insights into the evolution and function of sensory systems. This project will investigate responses of larval Anopheles gambiae(the malaria vector) to visual stimuli. Mosquito larvae and pupae are very mobile and readily respond to visual stimuli.Work on Zika mosquitoes(e.g. Mysore etal, 2014, Dev Dyn) indicated that, uniquely, larvae possess both the larval and the developing adult eyes, and both are functional in the later stages of larval development.Larval and adult eyes are predicted to express different photoreceptor types(Rocha etal, 2015, JEB), which, if true in malaria mosquitoes as well, will allow an easy genetic way to differentially target the two visual systems. In addition, work on adult (but not yet in larval) Zika mosquitoes demonstrated modulation of responses to visual stimuli by simultaneously presented smells(Vinauger etal, 2019, Curr Biol). Aims. 1)To characterise behavioural responses of A. gambiae larvae to visual stimuli from a broad range of spectral components, spatial and temporal frequencies. 2)To characterise the anatomy and function of larval and developing adult visual system by tracing neuronal projections into the larval brain, and by using RNAi against photoreceptor opsin genes. 3)To investigate modulation of visual responses by concurrent olfactory stimuli. Methodology. Behavioural assays will be conducted in transparent chambers, placed on top of small computer screens displaying visual stimuli, programmed in MATLAB.The larvae will be video-recorded and analysed in DeepLabCut, a Python-based open-source software that employs machine-learning based approach to behavioural classification.The student will be trained to program in MATLAB and use DeepLabCut by VN, who is an expert in binocular insect vision and cognition.The stimuli will be developed in collaboration with NHI, who is an expert in insect colour vision and visually-guided behaviours.The contribution of olfactory stimuli will be assessed by placing larvae in a solution of an odorant while presenting visual stimuli. RNAi knockdowns will be conducted by feeding larvae with dsRNA/chitosan nanoparticles.The anatomy of the visual system will be analysed by immunohistochemistry and confocal imaging at all larval stages.Projections of visual neurons into the brain will be imaged in transgenic larvae on a light-sheet microscope. Timetable(excluding general DTP events). Year 1, M0-3: Learning MATLAB and DeepLabCut in VN lab(Newcastle) and visiting NHI(Exeter) to design visual stimuli; M4-12: Aim 1 in Durham; M10: Progress meeting with NHI; M10: Light Microscopy School(York); Year 2, M1: SfN conference, USA; M1-3: PIPS placement; M4-12: Aim 2 in Durham; M8: Optical Imaging and Electrophysiological Recordings in Neuroscience School, Paris; M10: Neuroethology Congress, Germany; Year 3, M1: visiting VN(Newcastle) to modify stimuli presentation software for visual-olfactory assays; M1-12: Aim 3 in Durham; M8-10: MBL course on Neural System and Behavior, Woods Hole, USA; Year 4, M1-12: finishing up experiments and writing up. Novelty.Previous research has mostly focussed on adult mosquitoes, but very little is known about visual anatomy and behaviours in mosquito larvae.Given recent developments in microscopy and genetic tools, it is timely to address significant gaps in the study of larval vision in holometabolic insects",,2024,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P21416,2749566,A conflict of interests: How do viruses manipulate their mosquito-vector to increase their own transmission?,"Mosquitoes can be hosts for several different pathogens such as Zika virus, West Nile virus, and dengue virus. These viruses are becoming increasing threats to global health. Understanding how these viruses affect their mosquito host is essential for the development of accurate risk assessments and arbovirus surveillance and control. Hosts and their pathogens are often in conflict for their optimal survival strategy. Because of this some pathogens have evolved ways to manipulate their hosts behaviour. An example of this is dengue virus which reduces the mosquito's biting efficiency. This causes the infected mosquito to have to bite more frequently to reach similar blood repletion, which results in an increased spread of dengue virus. It could also be beneficial for a pathogen to manipulate mosquito temperature preference as the optimal temperature for the mosquito and their pathogen is in many cases not the same. The aim of this project is therefore to investigate how, and to what extent, viruses can manipulate the temperature preference of their mosquito-vector. This research has three objectives: First, asses the timescale, range, and extent of the manipulation by infecting mosquitoes and letting them choose between different temperatures in a two-chamber apparatus. Second, to model the effects of temperature-preference manipulation by adapting existing temperature extrinsic-incubation-period models. Finally, determine the mechanism of manipulation using RNA interference techniques and physical manipulation. This research will provide valuable new insights into viral mosquito manipulation and will allow us to create mosquito-behaviour-aware risk models that can be used to focus mosquito surveillance and control efforts.",,2026,N/A,,Disease Vectors | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector biology",2022 +P21418,EP/Y023633/1,a research and InNOvation Partnership for enhancing the surveillance and control of mosquito VECtors of emerging arboviruses,"Over the past 10 years, arboviral diseases, such as dengue, Zika, chikungunya and yellow fever, have (re)emerged with increasing prevalence and severity. Although these arboviral diseases are more prevalent in tropical countries, increasing numbers of autochthonous cases are being reported from European countries; hence raising concerns about the potential for the establishment of these pathogens in temperate regions. In the absence of effective vaccines and treatments, preventing these diseases at the global scale continues to depend largely on controlling mosquito vector populations, interrupting human-vector contact or both. Unfortunately, the recent resurgence of Aedes transmitted arboviral diseases worldwide highlights the limitations of current vector control to prevent epidemics and to reduce the incidence of diseases. New, affordable, scalable and community-based vector control measures are urgently needed to prevent the introduction, spread and establishment of Aedes-borne diseases in Europe and beyond. The INOVEC project proposes to build a large pan-European, cross-sectoral and multidisciplinary network to develop, optimise and promote integrated approaches and innovative tools for the surveillance and control of mosquito vectors of emerging arboviruses. INOVEC will gather 21 academic and non-academic institutions specialized in vector biology, social sciences and product development to stimulate basic and applied research, strengthen capacities, promote career development and facilitate knowledge and technology transfer to countries at increasing risk of arboviral diseases. INOVEC has the commitment to coordinate and integrate sectors in order to maximise impact, raise awareness of policy makers and stakeholders, and participate in the improvement of innovation potential at the European and global level. INOVEC will contribute to international efforts to improve global health and human well-being by reducing the burden of vector borne diseases.",,2026,N/A,,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P21419,2589920,Immune evasion strategies of (+)RNA viruses,"Lipid droplets accumulate in cells to serve as storage organelles. However, upon infection various immune complexes involved in innate immune responses are enriched on the lipid droplets. In particular, substrates that are modified by interferon stimulated gene 15 (ISG15) - a post translational modifier closely related to ubiquitin - are dramatically increased on lipid droplets when macrophages are either infected or treated with type I interferon. Many viruses encode for de-ISGylase enzymatic activities (e.g coronaviruses) or utilise a host de-ISGylase to hydrolyse ISGylated proteins and utilise lipid droplets for replication/assembly of viral progenies. This project will investigate whether lipid droplets have a direct role in cellular immune responses during virus infections via two specific questions: Aim 1: Whether lipid droplets serve as innate immune signaling platforms during virus infections. We will use a combination of mass spectrometry and biochemical/cell biological assays to characterise the proteome of lipid droplets when cells are stimulated with interferon-I or infected with wild-type or mutant flavi/coronaviruses and measure their impact on specific immune signaling cascades. Aim 2: Understand the mechanism by which viral proteases (or other viral factors) are able to subvert these responses, such as by hydrolysis of ISG15 modifications from LD-associated proteins to evade innate immune responses. To address both the questions we will use epithelial cells and monocyte-derived macrophages that serve as targets of both flavivirus and coronavirus infections. Infection will be performed with specific strains of viruses (e.g. the African and Asian lineages of Zika virus), which display distinct abilities to suppress host innate immune responses and hydrolyse lipid droplets, to characterise differences underlying this phenomenon.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P21420,2898927,Elucidating the antiviral mechanism of graphene oxide,"Graphene and graphene-related materials have attracted huge attention in recent years due to their unique and outstanding properties. Among these, graphene oxide (GO) has great potential in biomedical applications, such as drug delivery, tissue engineering, and bioimaging due to its good biocompatibility, water dispersibility, and the presence of various functional groups for further functionalisation with other molecules. On the other hand, GO was found efficient for capture and destruction of EV71 and H9N2 viruses and releasing viral RNA at elevated temperature, which demonstrated the antiviral activities of GO. Recently, we have developed a new method to synthesize high quality monolayer GO at a range sizes, and our preliminary results indicate that GO is not toxic to human cells but has size-dependent inhibition of SARS-CoV-2 pseudotyped virus. In this study, we will investigate in detail how the lateral size of GO affect its antiviral activity and GO's antiviral mechanisms using native viruses of global health significance (e.g. Zika virus, respiratory syncytia virus, influenza virus) and a pseudotyped virus system we recently developed for high-risk viruses (e.g. SARS-CoV-2) at a reduced risk level with H&S approval. GO samples will be synthesised and interaction between GO and viruses will be studies using various virus and cell viability assays and characterised using a range of physicochemical characterisation techniques. Taken together, this project aims to understand GO's property (efficacy and toxicity) towards viruses i.e. if it is GO size-dependent, and the molecular mechanisms of GO antiviral activity. This multidisciplinary project will provide an excellent opportunity for a self-motivated student to learn and develop many essential experimental skills and knowledge in biochemistry, cell biology, virology, and materials characterisations. The results of this study may provide important insight in detecting and diagnosis of viral infection, prevention and/or therapy of viruses of global health importance including that of the COVID-19 virus.",,2027,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21421,2402834,Probabilistic prediction of disease outbreaks with application to operational warning systems for infectious diseases in Brazil,"A useful intervention and prevention method for mitigating impact from infectious disease is the use of early warning systems, particularly in order to alert for possible epidemic outbreaks. This is currently in place for diseases like dengue, zika, chikungunya and severe respiratory syndrome (SRAG) in Brazil. These warning systems would ideally use counts of the number of people currently infected with the disease in order to determine whether an alert should be sent out. These alerts mean that procedures such as the allocation of resources can be carried out in a way that is suitable to the severity of the disease outbreak that is occurring. However, the actual number of cases of the disease on a given day is almost always not known. This is caused by two main problems: the under-reporting of disease counts and the delayed reporting of disease counts. Delayed reporting is when only a proportion of the disease counts are available immediately after they occur, while the rest of the counts eventually become available but too long (sometimes months) after they have occurred. Hence, the total disease count becomes known eventually but not in time to use in a warning system. Moreover, this total count is usually not the true disease count due to some cases never being reported (under-reporting) which can happen for several reasons such as individuals being incorrectly diagnosed or not seeking medical advice. This project involves research on developing a comprehensive statistical modelling framework for correcting and predicting disease counts for use in early warning systems, with specific application to such systems in Brazil. Current state-of-the-art approaches to correcting delayed reporting are either too inflexible or too computationally intensive to be of optimal use in practice. This work aims to develop a new framework, that brings the ""best of both worlds"", i.e. modelling flexibility and practical feasibility, while at the same time introduce new elements such as correcting for under-reporting and the incorporation of suitable predictors.",,2024,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae | Novel Pathogen,,,,,,,,,Zika virus disease | Disease X | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2020 +P21422,EP/X025535/1,SuperSIT - Sustainable Sterile Insect Technique,"New, clean, safe, and more effective methods for controlling mosquito-borne viruses are urgently required. One attractive approach is to release sterile male mosquitoes to mate wild females, thereby reducing their reproductive potential - the Sterile Insect Technique (SIT). However, SIT requires frequent releases of very large numbers of such males. A radical new SIT variant is proposed, which is sustainable and persistent - SuperSIT. If successfully developed and deployed, this will provide the established (by the PI and others) benefits of effective, environmentally-friendly, species-specific control, while dramatically (20-100x) reducing the number of sterile males needed, thereby reducing cost of delivery. Much improved environmental persistence will also reduce the vulnerability of the SIT to interruptions; together with reduced resource requirements and the possibility of low-cost, local deployment even in resource-constrained settings, this makes the method much more sustainable than current alternatives. The new approach will be developed in Ae. aegypti, the main vector of (e.g.) dengue, chikungunya and Zika, exploiting specific biological features of culicine mosquitoes that facilitate development, and the PI's long experience of applied insect synthetic biology. The project comprises five Objectives, of which three are independent, parallel synbio paths to providing the novel genetic traits of the SuperSIT concept. This parallel approach mitigates development risk in this ambitious, high-risk/high-return project. Another Objective aims to provide a complementary strain to facilitate mass-production, while the final one incorporates the sophisticated, iterative testing of the novel strains. Substantial preliminary data support each necessary step in the programme. The aim of this project is to develop initial prototype strains and assess their performance in laboratory cage experiments; no field releases are envisioned within the scope of this project.",,2028,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P21423,2739762,Mosquito-borne viruses; targeting the bite.,"The climate crisis is making mosquito-borne virus infections an increasing threat to human health. These viruses, such as those that cause Zika and dengue, are infecting more people and spreading to new countries as the climate warms and globalisation helps mosquitoes spread. Defining common determinants of patient susceptibility to this large group of heterogenous pathogens are key for informing the rational design of new pan-viral medicines. Mosquito-borne viruses are transmitted to people when biting mosquitoes spit virus into the skin. This is a key stage of infection that is common to all such infections. We have recently shown that mosquito-derived factors in mosquito saliva, co-injected with virus, have a highly significant enhancing effect on infection. Excitingly, we have already identified one salivary factor, sialokinin (SK), that is part-responsible. SK works by inducing blood endothelial barrier dysfunction, which enables a super-influx of leukocytes into the bite, which consequently become infected and replicate virus. Objectives This project will transform our understanding of this key stage of mosquito-borne virus infection with the aim of identifying a novel pan-viral therapeutic strategy by, 1.) defining how factors in mosquito saliva, including sialokinin, modulate blood endothelial barrier function, and so modulate host susceptibility to virus 2.) defining whether vaccination of mice against factors in mosquito saliva can interfere with its ability to enhance virus infection Experimental approach - we will utilise a combination of approaches to 1.) define the parameters by which saliva induces barrier dysfunction in primary cultures of blood endothelia (barrier function assays and transcriptome analysis) 2.) undertake a targeted siRNA-based screen of mosquito salivary genes to define the role of identified salivary genes in modulating endothelial barrier function (in vitro, in vivo and in cultured human skin explants) 3.) target mosquito salivary components with IgG-inducing vaccines in vivo This interdisciplinary project will uniquely combine immunology, vector biology, virology and vascular biology. It has potential to inform our understanding of virus transmission at the arthropod/mammalian interface and the development of novel vaccines that target mosquito saliva to reduce disease burden. The use of anti-saliva vaccines may have wide applicability, as enhancement of infection by saliva is widely observed for these viruses.",,2026,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P21424,NE/T013664/1,"Mosquitoes populations modelling for early warning system and rapid response public by health authorities correlating climate, weather and spatial-tem","As a result of the recent climate changes, mosquito-borne diseases (like Zika, dengue) are becoming endemic not only in sub-tropical regions of Africa and Latin America but in other parts of the world. This project will combine public health, mobile technology and climate modelling to evaluate the impacts of environmental changes on water providing breeding habitats for mosquitoes in Northeast Brazil. We aim to develop a series of spatial-temporal models to predict the burden of mosquito populations by deploying cutting-edge mobile and internet of things (IoT) technology leveraging multiple data sources from newly acquired climate, weather, mosquito surveillance, water and sanitation and socioeconomic data. This technology will include the use of mobile surveillance apps using gamification and citizen science technology co-developed with local stakeholders for reporting locations of water breeding points in Brazil. We will develop a data-driven early warning system to predict changes in occurrence and abundance of mosquito breeding points. This real-time system will alert public health and environmental authorities to mobilise community engagement for the prevention and rapid response to vector outbreaks. We will also develop educational content for public and community stakeholders to increase awareness of mosquito breeding habitats and water management. With public health stakeholders (WHO and Recife City Hall), we will co-develop community engagement strategies and evidence-based policies to improve standing water management and treatment. Most importantly, building on existing partnerships in the provinces in Northeast Brazil, where mosquito-borne diseases are endemic, we will work with academics and local stakeholder partners from Recife, Olinda and Campina Grande, and have a unique access to mosquito surveillance data to calibrate our predictive models in real-time via mobile app and IoT devices. Access to real-time datasets will not only provide a unique method for calibrating the predictive modelling results ? but also will put us in a position to evaluate the entire early-warning decision-support dashboard system with the authorities during their standard daily operations to ensure outstanding real-world impact on vector surveillance and public health policy. It is absolutely unique for a research project to have the opportunity to validate the research in the timeframe of the project while directly translating the results to public health authorities, policy makers, WHO, and stakeholders in Brazil, Turkey and other countries where vector-borne disease are soon to become endemic.",,2024,N/A,,Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Digital Health,,,,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience",Vector biology | Community engagement | Communication,2020 +P21426,BB/W002906/1,Usutu virus risk to the UK: Determining local vector competence and modelling climate suitability,"Usutu virus infects and causes large scale mortality in certain species of wild bird (such as blackbird and crows); but in recent years it has been recognised as zoonotic, infecting people, and causing fever and, in some cases, neuro-invasive disease such as encephalitis and meningoencephalitis. Usutu virus is spread by mosquitoes and is emerging throughout Europe. During the warm summer of 2020, zoonotic mosquito-borne Usutu virus was detected in two species of wild birds in Greater London. Furthermore, Usutu virus was detected over a long time period and in the non-migrating house sparrow, strongly suggesting that the virus has established in the UK and local British mosquitoes are transmitting it. The primary mosquito vector of Usutu virus in Europe, the Northern House mosquito, is present in the UK where it feeds predominantly on birds. Recent studies have shown that a laboratory colony of this species is competent to transmit the virus at warm temperatures. Therefore, our native mosquitoes may therefore be capable of transmitting it. In addition, other species of mosquito present in the UK feed on both birds and humans and may therefore be capable of spreading the virus from the bird reservoir to humans. The ability of these species to transmit Usutu virus in the wild is not known. The overall aim of this proposal is to assess the risk to the UK of local and invasive mosquitoes transmitting Usutu virus to birds and humans, at realistic UK temperatures. Using these results, we will then mathematically model the suitability of the UK climate, in conjunction with data on the geographical range of local mosquitoes and reservoir bird species. This will yield risk maps, showing where and when Usutu virus is capable of being transmitted in the UK. At the end of this project, we will have collected extensive data on Usutu virus and the ability of our mosquitoes to transmit it. This will put the UK in a stronger position to effectively manage an outbreak, should one occur in the next few years. Some of the data will also inform on other mosquito-borne viral threats. As demonstrated by bluetongue in northern Europe, West Nile across the world, and Zika in South America, arboviral threats can appear suddenly and spread quickly. Basic research in advance is needed if such outbreaks are to be effectively contained with minimal impact on human and animal populations.",,2025,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P21428,2863002,Understanding the role of Animals as preditors of disease,"A mountain of evidence in the scientific literature suggests that biodiversity provides important ecosystem services for humans. One aspect that has been particularly well studied is agricultural pest control, where animals such as birds and bats are often known to save farmers hundreds of dollars per hectare per year. However, an often overlooked ecosystem service that animals may provide is the consumption of insect disease vectors, which may literally save lives. Insects that act as vectors, such as mosquitoes, are the deadliest animals on the planet, due to their role in the spread of diseases such as malaria, dengue fever, yellow fever, African sleeping sickness and others. These diseases alone account for more than 600,000 human deaths every year, in addition to suffering by hundreds of millions of people that contract the diseases but subsequently recover, and the economic burden of caring for them and lost productivity. Other diseases spread by insect vectors can be life altering (e.g. Zika virus). Some progress has been made in controlling vectors like mosquitoes, particularly through the use of insecticides. However, insecticides can have negative outcomes, such as killing key crop pollinators, harming other members of the food webs such as insectivorous birds, and evidence suggests that vectors can and do evolve insecticide resistance. Natural predators of vector insects are poorly understood. For example, bats are known to be voracious consumers of mosquitoes, potentially removing up to 600 from the environment every hour, but it remains unclear which species they may be consuming (disease vectors or those that are relatively benign). Our DNA sequence data from bird and bat faecal samples collected from Cameroon show that at least 15 species of bats and birds consume mosquitoes from five different genera, including Anopheles, Culex, Coquillettidia, Eretmapodites, and Mansonia, which include important human disease vectors. However, our data remain incomplete, because it is very difficult to assign species-level taxonomy to insect vectors using current methods. Thus, this project aims to: 1) In collaboration with project partners, develop a DNA metabarcoding system that can identify vector insects to species level 2) Employ the newly developed approach to identify animals consuming insect vectors - focusing on birds and bats, but potentially also amphibians, reptiles, and predatory insects 3) Use network and ecological modeling approaches to investigate the food webs that these species participate in, and perform sensitivity analyses to answer questions such as: What would happen if one or more predators were removed (e.g. due to land use or climate change)? What would happen if one or more vector species were removed from the system (e.g. due to vector control strategies)? The student will leverage our massive collection of more than 2000 bird, bat, and amphibian samples already in hand from our on-going projects in Cameroon, Ghana and Zambia. In the lab, the student will conduct a literature review and employ public databases to find potential genetic regions with sufficient resolution to identify species-level taxonomy of insect vectors, and design/test candidate metabarcoding PCR primers from these regions. Once a suite of primers has been developed, and using a primer set developed by project partners, the student will conduct DNA metabarcoding of bird, bat, and potentially amphibian, reptile and predatory insect samples (i.e. simultaneous sequencing of all potential insect vector prey) using advanced DNA sequencing technology. These sequences will then be compared to our reference sequence database to assign taxonomy using sophisticated bioinformatics pipelines. Data will be analysed in ecological community networks as well as in a dynamic ecological modelling framework we are currently developing to link species interactions and abundances",,2027,N/A,,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P21434,2431727,Modelling vector-borne disease epidemic risks using forward climate projections,"A large amount of work has been done in the field of vector-borne diseases. Work from here can be used to build models for vector-borne diseases of interest (such as Zika virus or Dengue fever). This is a very frequently researched area and so models of these diseases are robust and have been shown to make sensible real-world predictions. Studies have also been done on climate dependent mosquito population models [3,4]. These models vary in their complexity and include parameters such as temperature, humidity and rainfall to provide forward projections for the population of mosquitoes. Such models can be used in this project and embedded within the aforementioned epidemiological models to create systems where climate varying epidemic risks can be studied. These models have been used to estimate the reproduction number of a disease and to simulate outbreak dynamics but not to estimate the risk that early cases generate an epidemic. The IER is frequently examined because it is a very standard result in epidemiology and is widely used in many studies [5], particularly those in which climate effects on epidemic risks are not accounted for. The IER is often computed using a population model embedded inside an epidemiological model as detailed above. However, there is very little work done on the CER. The CER has been examined in a basic host-vector model but this only allows for varying death rates (and not varying population of mosquitoes) [6]. Studies on the CER do not use climate change forward projections, and instead focus on local change in climatic conditions over the course of a year. This research fits well into the broader context of the field because very little work has been done on the CER with none having been done using real-world climate projections. This project aims to answer several questions in the field of epidemic risk and vector-borne diseases. Are vector-borne diseases more likely under a changing climate? Is it the case that climate change uniformly increases the risk of large outbreaks of vector-borne diseases occurring or are there geographical areas where the risk is likely to decrease? What is the distribution of regions that are high and low risk? Other questions to be answered include, is the IER a suitable approximation for the epidemic risk or does the CER need to be computed? Can these two theoretical quantities be related to practically useful outbreak risk metrics, such as the probability of an outbreak exceeding a certain number of cases? How much variation is there in epidemic risk in a given region when the initial conditions for the climate simulations are varied? Do there exist places where the epidemic risk is consistently high or consistently low? This research closely relates to the EPSRC in both content and wider goals. The content is in the field of mathematical epidemiology where novel methodologies will be used to construct a mathematical framework for predicting the outbreak risk of vector-borne diseases. This project also extends to the physical sciences (due to climate change data), living with environmental change and global uncertainties. Particular emphasis will be placed on communicating research outcomes with both the external partner and the scientific community as a whole. There is also potential for public outreach and generating awareness of the topic. Research areas; Global uncertainties, LWEC [Living With Environmental Change], Mathematical Sciences, Physical Sciences External Partner; Colorado State University, and National Center for Atmospheric Research, USA",,2024,N/A,,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,Epidemiological studies,Disease transmission dynamics,2020 +P21435,MC_PC_22014,Proposal to address the medium- to long-term EBOLA associated psychological Distress and psychosocial problems in Mubende District in central Uganda (Ebola+D Project),"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2024,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P21436,2434414,Local perceptions and military-assisted health interventions in conflict settings,"This project aims to investigate and raise critical awareness of how local perceptions can influence responses to epidemics in conflict settings, particularly those assisted by the military, in order to improve the effectiveness of future health interventions. In recent high-level meetings in the UK and the US, policy-makers, academics, practitioners and military actors determined that there was need for additional research exploring how local communities feel about civil-military relations, particularly in health responses in conflict settings. While previous research has analysed, on the one hand, the significance of local perceptions within health interventions, and on the other hand, the limitations of civil-military coordination in conflict settings, there is currently limited research that examines the intersection of these two issues. This research project proposes to focus explicitly upon this crucial juncture and thereby address a significant gap in existing academic and policy literature. To carry out this analysis, this project will examine the currently ongoing Ebola response in the conflict affected eastern part of the Democratic Republic of the Congo (DRC). Local perceptions are generally undervalued and unaddressed in the Ebola response activities led by the Congolese government and World Health Organization. This is despite significant evidence suggesting that certain response approaches and the presence and involvement of military actors within the health intervention are leading to community resistance to response activities. This project proposes to explore exactly how the perceptions of local community members in the DRC are shaping the dynamics of the military-assisted.",,2023,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P21437,2594491,How can decentralisation strengthen the responses to public health emergencies? Evidence for West Africa,"Based on the argument that centralised systems are unable to coordinate large-scale activities due to lack of knowledge about local culture and circumstances, decentralisation has been central to health services development and reform in developing countries since the 1970s. What is less well understood is the impact decentralisation has on a country's ability to effectively respond to public health emergencies or on the important related concept of health system resilience - the capacity to prepare for and effectively respond to crises while maintaining core health system functions pre-, during, and post-crisis. This is particularly relevant in the current climate of an ongoing pandemic in which there is little consensus on the most effective response. This project addresses this gap by exploring the links between decentralisation, health system resilience, and effective public health emergency responses through an analysis of decentralisation reforms in Liberia, Guinea, and Sierra Leone and their role in the responses to the 2014-16 Ebola outbreak. Health system resilience is especially important in countries with high levels of poverty or instability where people are highly vulnerable to shocks associated with ill health, including major epidemics. This is particularly relevant in Africa due to the frequent and widespread occurrence of epidemics and disasters. Liberia, Guinea, and Sierra Leone provide an ideal case due to their recent shared experienced of responding to Ebola, where a central lesson was the need for a comprehensive strategy with communities at the centre and decentralized programming to facilitate flexibility and adaptation to the local context. Due to their similar social and economic structures but sharply dissimilar political records, these countries have an obvious appeal for comparative analysis; they have substantial variation in terms of decentralisation but share relatively constant confounders due to being in the same region. The research objective of this project is to determine whether health system decentralisation leads to more effective responses to public health emergencies. To this end, it asks the following research questions: What constitutes an effective response to public health emergencies? What is the role of health system resilience in achieving this? How does decentralisation help to build a resilient health system? Which aspect of decentralisation is most likely to shape resilience and effective responses to public health emergencies? This project uses a mixed methods approach. Quantitative research methods examine the relationship between decentralisation, health system resilience, and public health emergency responses in Liberia, Guinea, and Sierra Leone, using structural equation modelling (SEM) and directed acyclic graphs (DAGs) to compare how the WHO's six health system building blocks impact emergency responses. SEM allows for paths to be drawn between latent variables while DAGs are used to represent the structure of the causal networks linking exposure, outcome, and confounders. The independent variable - decentralisation - is measured by an index of different variables of fiscal and political decentralisation. Dependent variables comprise metrics for public health emergency responses such as Ebola cases, deaths, testing, and number of treatment facilities. Qualitative methods are used to gain understanding of the political economy of decentralisation in Liberia. As the country with the highest number of Ebola deaths and as the last country to be declared Ebola-free, the Liberian case presents an opportunity to analyse the barriers to delivering a more effective response and what drives these. Primary data will be collected through interviews with government officials, development partners, and decentralised healthcare providers focusing on the context, key actors, and motivations for decentralisation reform at the national macro-level and regional sector-level.",,2025,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",,2021 +P21438,54670,Development of Viral Inactivation Buffer for the transportation of viral contaminated samples,"Current Covid-19 testing of patient samples follows guidelines published by the World Health Organisation (WHO), which have been followed by health organisations in developed countries such as the National Health Service in the UK and Centre for Disease Control (CDC) in the USA. These protocols all transport virus 'live' in a cell preservation media that must be kept cool (2 -- 8°C) and has a limited life due to degradation. These samples are potentially infective and necessitate handling as Class Level 3 pathogens from when they are collected from the patient, through shipping, to inactivation in the initial processing at analytical laboratories. This limits the number of laboratories that are able to perform sample testing. During previous Ebola outbreaks (another RNA virus), methods were developed to allow sampling that denatured samples by immersion of swabs in a chemical denaturant that killed the virus and allowed processing by laboratories at a significant reduction in risk in the supply and analysis chain. This methodology of denaturation of swabs by immediate immersion in high molarity guanidine thiocyanate solutions has been shown to be effective in denaturation of both Ebola (with the addition of detergent) and Influenza A viruses and is compatible with high throughput processing in labs. Validation of a viral inactivation buffer (VIB) for Covid-19 samples would not only reduce the risk throughout the analysis chain from sampling to analysis, but also increase the number of laboratories able to process these samples at the lower risk category, with a significant reduction in processing time and the ability to test larger volumes of samples at a local level. This methodology has also been shown to increase the stability of samples, reducing the need for cold shipping and improving sample consistency due to the denaturation of RNAses within the samples.",,2021,LIFE SCIENCE GROUP LIMITED,61846.24,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21439,2567669,What does a disability-inclusive pandemic response mean for Liberia and how can it lead to genuine systemic change?,"It is widely recognised that people with disabilities are disproportionately affected by COVID-19 (FCDO,2020; UN,2020a). Yet there is limited empirical evidence on the ways and extent to which the response itself has affected the lives of disabled populations in low-income settings, and how this compares to other epidemics. This research compares how people with disabilities experienced outbreaks of two widespread infectious diseases in Liberia (Ebola and COVID-19). Liberia has high levels of multidimensional poverty. The country is still reeling from the 2014-2015 Ebola outbreak in West Africa, which killed nearly 5,000 people with over 10,000 confirmed cases, and is now grappling with COVID-19. Like many countries, the Liberian Government implemented extensive measures to curb the spread of COVID-19, including lockdowns and enforced social distancing. These have negative implications for people with disabilities (FAO,2020), and COVID-19 is likely to exacerbate pre-existing barriers (UN,2020b). However, while there is a raft of guidance on how to include people with disabilities in the COVID-19 response (UN,2020a,2020b; WHO,2020), there is little empirical evidence of the impact this has had on disabled populations in low-income settings. This proposal builds upon previous DFID/ESRC-funded research. It will examine how people with disabilities can achieve meaningful inclusion in epidemic and other humanitarian responses, and how trust in government - a critical driver in public health compliance - and the capacity of health systems to deliver health messages and services can be developed. This research will gather in-depth qualitative data, taking an intersectional approach to analyse inequalities in disability and public health crises, examining issues including gender, impairment and poverty.",,2024,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Gender,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2021 +P21440,2605079,The Microbiome and Vaccine Response,"The human gut harbours a complex microbial ecosystem that plays an important role in shaping the host immune system. One area that has yet to be fully explored is the ability of the gut microbiome to influence the efficacy of T cell vaccines through direct, or indirect influences on CD8+ T cell responsiveness. This studentship will seek to understand and exploit the ability of commensal gut microbes to influence the human immune response to T cell vaccination. This is an interdisciplinary project that will begin by combining trials of viral vaccines (e.g. HIV and Ebola vaccines) with in-depth multi-omic analysis to identify functional variation in the gut microbiome associated with immunological markers of vaccine success. It will progress to using in vivo models to study the potential of specific microbes (or microbial products) as adjuvants to improve T cell vaccine response. The studentship will develop interdisciplinary skills in immunology, computational biology, and use of in vivo models as a basis for studying immune-gut microbiome interaction.",,2025,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Clinical trial (unspecified trial phase) | Characterisation of vaccine-induced immunity,2021 +P21441,MR/V02213X/1,Visualising Glycoprotein Interaction Dynamics,"In our cells, the functions that are vital for life-from fighting infection to replicating DNA-are carried out by proteins. These are regulated by a complex array of mechanisms, including protein-protein interactions and chemical modifications. A common protein modification is glycosylation-an intricate, non-template driven process that adds complex carbohydrate molecules, or glycans, to individual amino acids. It is estimated that half of human proteins are glycosylated, and glycan structures have a huge impact on the protein. By interacting with other proteins and biomolecules, glycans bound to a protein can alter that protein's structure and function, where it is goes in a cell, and its homeostasis. The importance of glycoslation is illustrated by a set of human conditions known as the Congenital Disorders of Glycosylation, where mild defects in glycan biosynthesis lead to severe multisystem malfunction, organ failure and even premature death. Glycosylation is highly relevant to the biopharmaceutical industry. It affects the safety and efficacy of monoclonal antibodies and other therapeutic 'biologics'-a rapidly growing class of drugs for treating conditions including cancers and autoimmune diseases. Glycans are also of central importance to many viruses, including influenza and Ebola, which evade our immune systems by hiding under a dynamic, dense 'glycan shield'. Despite the clear importance of glycosylation, we know surprisingly little about how glycans influence the properties and interactions of the proteins they are bound to. One of the main reasons for this lack of knowledge is simply that glycans are very difficult to study. They form a bewildering array of complex, dynamic structures, and their analysis eludes even today's most powerful tools. Due to the prevalence of glycoproteins in biomolecular interactions, unravelling their inherent structural complexity in order to understand protein function is fundamentally important but requires creative and pioneering methodologies. I plan to address the current critical lack of tools by developing an approach that combines existing techniques in a new way, creating a powerful method for capturing the interactions that take place between glycans and other molecules. Our approach will combine chemical crosslinking-which makes it possible to monitor even short-lived protein interactions or dynamical properties but is currently unsuited for glycans-and metabolic glycoprotein engineering-to incorporate chemical 'tags' into glycans that will enable crosslinking. We will also use cutting-edge computational and single-molecule mass measurement techniques to gather complementary data to help us interpret the information from the crosslinking approach. As part of this work, we will apply our new approach to study glycosylation in influenza, Ebola glycosylation, human antibody-receptor recognition and monoclonal antibodies, thus expanding our knowledge of glycan function in health, disease and drug development. The aim of my Future Leaders Fellowship is to transform our ability to study and visualise glycoproteins. I believe that we can create the tools we need to address complex long-standing biological questions involving glycoproteins, and I plan to develop such a tool. My approach will enable new biological discoveries by providing an unprecedented level of detail about glycoprotein interaction dynamics. In addition to the important discoveries anticipated to arise directly from this project, the method represents a paradigm shift for the study of glycoproteins.",,2025,N/A,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P21444,2435782,Bayesian Inference under the Structured Coalescent Model,"The coalescent is a population genetics model for the inheritance of genetic material over time. Genetic sequences are taken at known times and based on genetic similarities between sequences, the times until pairs of lineages coalesce at a common ancestor can be estimated. An important factor, which is not accounted for in the ordinary coalescent model, is the spatial constraints. For example, if two lineages have been separated geographically at some time in the past, they cannot find a common ancestor until both lineages exist in a common location. This motivates an extension to the ordinary coalescent model which factors in spatial constraints, known as the structured coalescent. Individuals are assumed to exist in a fixed, and possibly unknown, number of distinct demes, with migrations occurring between demes at fixed rates backwards in time. A dataset consists of a number of genomes sampled at various timepoints and from various demes. From this, there are several evolutionary parameters which we would like to infer in the structured coalescent model, including the migration rates between demes and effective population sizes of each deme. The migration history that led to the current locations of the samples is also often of interest. The uncertainty in at least some of these parameters is likely to be important, which motivates a Bayesian approach to inference. Current methods to infer these parameters are either computationally expensive, or rely on approximations of the structured coalescent in place of the full model which can introduce significant biases (Muller et al, 2017). To combat this lack of scalable approaches to perform inference under the structured coalescent, I intend to construct a reversible jump Markov chain Monte Carlo algorithm which will infer migration histories and evolutionary parameters for a fixed coalescent genealogy. There are multiple robust methods currently available to infer a genealogy from genomic data, including BEAST (Suchard et al, 2018), LSD (To et al, 2016) and TreeTime (Sagulenko et al, 2018). My work will build upon previous MCMC schemes proposed by Drummond et al. (2002) and Ewing et al. (2004) for the coalescent and structured coalescent respectively. Further, I will release an implementation of my algorithm as an open source R package. The correctness and computational efficiency of my algorithm will be assessed by benchmarking on simulated datasets. Applications to state-of-the-art real datasets from infectious disease pathogens will demonstrate the usefulness of my algorithm, for example a global dataset of cholera genomes from the seventh pandemic (Didelot et al 2015) and a collection of Ebola genomes from the 2013-2016 West African epidemic (Dudas et al 2017). I anticipate that this project will contribute to advances in the accuracy of statistical methods for genetic sequences. It will also be relevant for generic MCMC methods on constrained and non-Euclidean spaces, which have applications across applied sciences and engineering.",,2024,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P21445,2597405,Synthesising behavioural and epidemiological models and their methodologies to simulate predictive spread of infectious diseases,"The context of the research: In this study, I plan to synthesise and advance the methodologies guiding integrating behavioural and epidemiological models for human infectious diseases. The aims and objectives of the research: In this study, I plan to synthesise the methodologies guiding integrating behavioural and epidemiological models for human infectious diseases. The core research questions I aim to address include: (i) which behavioural mechanistic models in the human psychology literature should be considered when modelling behaviour related to adherence of control strategies; (ii) which data are necessary to model human behaviour in the context of infectious disease outbreaks, noting that this may be disease and context specific; (iii) how can data collection be improved to meet the needs of disease modellers while not creating unrealistic resource expectations for stakeholders; and (iv) how incorporating behavioural mechanisms to infectious disease models affects the research findings and policy implications based on simulation studies. The novelty of the research methodology (if any): I plan to create an updated framework for modelling behaviour in infectious disease outbreaks. This research will enhance our understanding of the usefulness of data flows from various research domains and ways to synthesise them. The potential impact, applications, and benefits: This proposed project will provide a structural framework and model to better predict the spread of infectious diseases through considering human behaviour, thus leading to potentially better-informed models and research findings to inform policy decisions in the event of infectious disease outbreaks. The project encourages interdisciplinary approaches whilst establishing methodologies that future researchers may replicate and improve upon. How the research relates to the EPSRC remit: The proposed project relates to the EPSRC remit according to its research goals in mathematical biology. Specifically, the research relates to their goal of advancing techniques to investigate biological processes and systems since I will be studying the role of human behaviour in infectious disease outbreaks and generating a novel, integrated epidemiological and behavioural model. Into which EPSRC research areas does your research fall Mathematical Sciences Global uncertainties External Partner - World Health Organization (WHO) - Jonathan Polonsky and Olivier le Polain of the WHO have agreed to support the project in the roles of external partners. They have agreed to provide data if relevant to the project and to provide their expertise as needed to support the project. However, data from the WHO is not required for the project to progress. Specifically, they have indicated that they have a dataset from the 2018-2020 Ebola outbreak in the Democratic Republic of the Congo that they would be willing to provide if needed. In addition to the WHO, the Warwick Data Science Lab is a relevant group that have studied predicting human actions based on social media data and would be an excellent source to reach out to.",,2025,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2021 +P21447,2431836,Improving inference of pathogen transmissibility and effects of interventions during epidemics.,"The context of the research * The threat that infectious diseases pose to plants, animals and humans is one of significant consequence globally [1]. Control of infectious diseases through public health measures is an intensely researched area (due to their effectiveness [2]), particularly during the early stage of an epidemic. Since the turn of the century, continual tracking of the time-dependent reproduction number, R_t, has increasingly become more helpful to guide how interventions should change through time. R_t is defined as the expected number of secondary cases generated by an infectious case once an epidemic is underway [3]. This statistic indicates the magnitude of the intervention required to control the outbreak (e.g. the proportion of contacts that must be prevented for cases numbers to begin falling), for the given pathogen. Given perfect contact tracing information, inferring the time dependent reproductive number (at time t) would be as simple as counting the average number of secondary cases that a primary case generates at time t. It is important to note that we require real-time estimates to inform decision making but the 'perfect information' approach described here can only be generated retrospectively. In reality, such information is not available and instead, R_t inference is estimated using two types of data. One data type is incidence (number of new symptomatic cases), whilst the other concerns an epidemiological delay distribution between all infector-infectee pairs. The second piece of data would ideally be the generation interval (the distribution of delays from infection in a primary case to infection in a secondary case) and in which case the incidence data would be indexed to the date of infection. In practice, a proxy for the generation interval is used (owing to the complexity and ambiguity of determining exactly when an infectee becomes infected). This is the so-called the 'serial interval' (the distribution of delays between symptom onset in an infectorinfectee pair). To infer the time-dependent reproduction number accurately, one should then index the incidence data with date of symptom onset. Broadly speaking, there are two statistical methods ([5] and [6]) which a large number of studies base their R_t inferences on. Both of these methods use Bayesian inference techniques to generate time-evolving confidence intervals and expectations for R_t. This project will involve building on the work developed in [5]. Accurate and precise R_t estimation is of significance during an epidemic since it is the primary indicator of the necessary stringency of public health measures. Consequently, the lack of accurate or precise estimates can lead to either delays in bringing outbreaks under control (resulting in excess morbidity and mortality) in the event that R_t is under-estimated or conversely, unnecessary public health measures in the vent that R_t is over-estimated. Currently none of these estimates include non-static (time evolving) serial interval (the distribution of delays between symptom onset in an infectorinfectee pair) estimates. There is preliminary evidence ([9], [11]) to suggest that time evolving serial intervals may have a significant impact on R_t estimates. Aims: To improve the techniques that generate R_t estimates and to develop the understanding (within the field of mathematical epidemiology) about the significance (if any) of time varying serial intervals on R_t inference. Objectives: Develop a hypothesis on how characteristics of changing serial intervals will affect R_t inference. Investigate real world data (initially from the 2018-2020 Ebola epidemic in Beni Health Zone, North Kivu Province, DRC), where I can infer the reproductive number (with and without updating serial intervals) to test my hypothesis. Extend existing theory on R_t inference to incorporate heterogeneities into the model framework, e.g. spatial/age models External Partners - WHO",,2025,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease transmission dynamics,2020 +P21448,EP/T003650/1,Mathematical Modelling for Infectious Disease Dynamics and Control in East Africa (MMIDD-EA),"Computer-based mathematical modelling of infectious diseases is an essential tool to understanding how diseases spread. They can also be extremely useful in designing effective control strategies and policies. The East Africa region is a hotspot for emerging and endemic diseases caused by bacteria and viruses, including those spread from animals to humans (known as zoonoses). Despite the potential for mathematical modelling to address public health challenges in the region and the availability of relatively cheap computing power and free programming platforms, these skills are rarely applied by academics and researchers in low and middle income countries. Instead modelling work is done by researchers from high income countries and often for diseases threatening global health such as epidemics caused by the Ebola virus. We aim to develop a network of East-African based mathematical modellers to build skills and capacity so that this work can be performed for priority infectious diseases in the region and by local researchers, who have a superior understanding of the social, economic, geographic and political context of infectious disease spread and control. To do this we will organise three activities. First, we will develop and run an intensive short-course in mathematical modelling of infectious disease dynamics for 20 people in Kenya. Applications will be sought from researchers based in East Africa with skills in mathematics and an interest in quantitative approaches to infectious disease dynamics and control in humans and animals. A competitive selection procedure will prioritise candidates with both institutional support and defined modelling projects relevant to the region to carry forward. The course will be based upon the well-established and highly regarded Mathematical Modelling of Infectious Disease Dynamics residential course supported by the Wellcome Trust, led Dr Andrew Conlan (University of Cambridge) and modified to be appropriate to the needs identified in East Africa. The course will have a strong emphasis on building practical skills using the free software R and Rstudio, and focussed on infectious diseases that are important in the region. Second, five fellowships will be awarded to course attendees to enable them to further develop their skills. Each fellow will be matched to a mentor from the University of Cambridge or the broader course faculty (drawn from across the UK and Africa) who will work with them to develop their skills and collaborate on a selected modelling projects. The fellows will have the opportunity to spend up to 3 months in Cambridge (or other UK Institute, as befits their project and development needs) as well as the opportunity to spend time at the University of Nairobi and interact with their cohort. Third, we will support the development of an East African infectious disease modelling network, by linking with other complementary initiatives in the region. This will increase the self-reliance of the cohort and help to sustain further capacity building.",,2021,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,,,2020 +P21450,BB/X003256/1,Fast DNA Sequencing Using Near-field Microwave Sensors,"DNA is the nucleic acid that passes information from parent to child in living systems. Determining the order of the four information-carrying bases, (denoted A,C,G,T) is known as ""sequencing"". Such sequencing is at the core of modern molecular biology and genetic epidemiology and has huge potential for applications in diagnosis and precision medicine. Since the pioneering work that led to the first sequencing of the human genome about 20 years ago, sequencing technology has made enormous progress, significantly reducing time and complexity. Portable sequencing devices are now commercially available and have been fundamental, for example, for field-surveillance of Ebola virus in West Africa and rapid identification of SARS-CoV-2 (COVID19) variants. These portable devices are based on the motion of dissolved ions (charged atoms) through a tiny hole called a ""nanopore"", whose dimensions are in the order of a few nanometers, i.e. billionths of a metre. If DNA strands are present, they can also be made to flow through the pore, temporarily blocking the flow of ions. Each of the four bases forming the DNA modifies the ion flow in a slightly different way and therefore, by monitoring how the flow of ions changes over time it is possible to determine the sequence of the bases within the DNA. Nanopore sequencing is revolutionising the way we sequence DNA, but suffers from some limitations which are fundamentally linked to the ion current approach. In particular, although DNA can pass through the pore at a high speed (~1 million bases per second) it is not possible to monitor the motion of ions this quickly and therefore it is not possible to read the sequence in real time. Instead complex enzyme-based mechanisms must be used to slow down the DNA transit. In this project, we hope to achieve a transformative change in real-time sequencing rates by combining solid-state nanopores with a new way of identifying the four bases within DNA strands. To do so, we will use microwaves - electromagnetic waves oscillating at GHz frequencies. Microwaves are at the core of the information and communication technologies used in mobile phones, wi-fi and Bluetooth networks and GPS satellites to carry large amounts of information. Microwaves also interact with matter and can be used to probe molecules by measuring their unique electromagnetic fingerprints. Our proposed sensors will combine atomically-precise nanofabrication with the measurement accuracy offered by high frequency electronics. The device will consist of an atomically-thin conductor (graphene) shaped as a bowtie with a small gap at its centre. The conductor acts as a waveguide, enabling microwave propagation between the two ends of the sensor. The centre of the bowtie will be carefully aligned with a nanopore, so that, when DNA passes through the pore, it interacts with the electromagnetic field formed at the bowtie tips. We hope that each of the four bases forming the DNA (A, C, G and T) will comgating microwaves, allowing the sequence of bases to be read. This approach replaces the slow, ion-motion based electrochemistry currently used for nanopore sensing with fast communication-engineering technologies, with potential for a 1000-fold increase in speed. The sensor technology developed will have capabilities beyond sequencing, as it can be applied to analyse other molecules relevant for biochemistry and medicine. Thanks to the compatibility of our sensors with electronic chip fabrication technology and the ubiquitous use of microwave electronics for wireless communication, we envisage a seamless integration with already existing technology to realise portable sequencing and sensing tools.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P21453,BB/T002212/1,Mapping antibody class switch mechanisms and function,"Antibodies are produced by a specialised immune cell (B cell) and act as important immune mediators, bridging between pathogens and effector cells to protect us from infection. Antibody molecules can also exist bound to the B cell surface where they act as receptor for detecting target molecules (antigens). Their versatility is immense, they are used to make diagnostics, research tools and therapeutics. One part of the antibody (variable region) is responsible for binding to the antigen, the other end of the molecule is responsible for activating/mediating different functions in the immune system. Uniquely, the antibody variable region can evolve within the organism within a short timescale, in response to infection or vaccination, to improve its binding to the antigen. The constant region does not evolve, but it can be changed to one of 9 different classes or subclasses in order to change the function of the antibody in a genetic process known as Class Switch Recombination (CSR). The (sub)classes of antibody are arranged in the genome in this order: IgM-IgD-IgG3-IgG1-IgA1-IgG2-IgG4-IgE-IgA2; a B cell starts life with IgM and IgD and after activation switches to another (sub)class. Until very recently it was thought that CSR had no effect on the binding abilities of the Variable region. Recent research in different areas (Ageing, Ebola, HIV infection, Cancer) indicates that we don't fully understand the processes that control which (sub)class will be used, the difference that CSR between subclasses makes to the outcome of an immune response or the exact molecular effects that CSR might have on the variable region binding properties. Therapeutic antibodies are a critical pharmaceutical resource, being the fastest growing class of pharmaceuticals, with thousands now in the development pipeline. Current products with regulatory approval/undergoing regulatory review are mostly IgG1 whilst none are IgA or IgE. As we understand more about the functions of these classes, we may find that the potential utility of antibodies can be increased, such as IgE in skin cancers or IgA in gut-related disorders. In this programme we propose to harness the unique expertise of a team of bioinformaticians and immunologists to determine what factors, both outside the cell and inside the cell, control CSR. We will monitor how CSR progresses with time on a daily basis for a fortnight after challenge with the flu vaccine and we will use computer modelling of antibody structures to investigate how changing one side of the antibody molecule may affect the other. Each of these three main objectives will produce a range of results, some of which will help to understand the work in the other objectives, although would not be critical for their success. All parts of the programme require input from all the team to varying levels. The methods we will use and develop are ground-breaking, in our preliminary data, we show pathways of class switching to different types of antibody in cell culture on a single cell basis. We will alter the conditions of these experiments, note the resulting changes and map the protein-protein and gene interactions to deduce what molecules are controlling CSR. These methods will be applicable in all cellular Bioscience disciplines and will transform cell biology research. The mapping of human CSR and the molecular modelling of antibody structure will also result in new tools for others to use, we have successfully done this before and have large global user groups in several areas. The interdisciplinary nature of our team means that we have insight into how to design tools that are user friendly and flexible, all data and tools will be made publicly available in a collective resource ""BHive"". We will also run our programme in such a way as to maximise the interdisciplinary familiarisation across all our teams and ensure our ECRs have a springboard into their future careers.",,2022,N/A,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Data Management and Data Sharing | Innovation,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Characterisation of vaccine-induced immunity,2020 +P21455,5U01AI168287-02,Solving Opportunities for Spillover (SOS): Frequency and Mechanisms of Cross-species Transmission of Henipaviruses in Bangladesh,"Abstract Until and unless we better understand and prevent spillovers of bat-borne viruses into intermediate hosts and humans, we will be severely limited in our ability to stop pandemics. Henipaviruses are bat-borne, RNA viruses that spillover through this route. Nearly half of all reported human henipavirus infections have been associated with contact with sick domesticated animals, though our understanding of drivers of henipavirus spillovers and specific transmission pathways remains severely limited. Building on preliminary data about bat, domesticated animal and human infections, this multidisciplinary study integrates epidemiology, ecology, and anthropology to identify spillover pathways for henipaviruses into domesticated animals in Bangladesh and the risk they pose to human health. Our first aim is to identify drivers of henipavirus spillovers into domesticated animals in Faridpur, Bangladesh. We will use multiplex pan-henipavirus assays to identify infections in Pteropus medius bats and domesticated animals living nearby this roost through cross-sectional and prospective studies. Combined with intensive studies of bat-domesticated animal interactions and weather data, we will build statistical models to identify the relative contribution of each of these factors. Our second aim is to describe which henipaviruses are being transmitted from bats to domesticated animals. Serologic studies of animals in Bangladesh show that they are frequently infected with non-Nipah henipaviruses. Through surveillance for and sampling of sick domesticated animals, we will describe the specific viruses that spillover from bats in Faridpur. Our third aim is to determine the risk of henipavirus transmission from domesticated animals to humans. We hypothesize that undetected henipavirus spillovers in humans are occurring through contact with sick domesticated animals and will conduct cross-sectional and prospective serosurveys of humans who have close contact with sick animals in Faridpur. We remain ignorant about henipavirus spillovers through intermediate hosts â€Â"" including the specific viruses spilling over, the frequency and distribution of spillovers, and the pathways of transmission â€Â"" at our own peril. The knowledge gained from this study will be immediately applicable to human and animal health programs in Bangladesh and other countries where henipaviruses circulate in bats. By learning about which henipaviruses infect humans, and how they are infected, we can advise public health surveillance programs on how to optimize detection and epidemiologic investigation of cases across Bangladesh. Our investigations about spillovers in Faridpur can also be scaled- up to other areas of Bangladesh and countries where henipaviruses circulate in bats so that we can truly begin to appreciate the scale of henipavirus spillovers in the global landscape.",,2027,Johns Hopkins University,599947,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology,2023 +P21456,1R15AI180994-01,BITE (Bat Immunology Training and Education) - an undergraduate experiential program for developing the next generation of One Health scientists,"Project Summary/Abstract Without T cells (e.g., CD4+ helper, CD8+ cytotoxic), mammals cannot have a proper functioning immune system or fight off viral infection. Classically, T cells in mammals develop in the thymus then migrate to peripheral tissues and circulate in the blood. Development of T cells is critical for mounting antiviral response cytokines, immune memory, regulation, pathogen recognition, activation of B-cells to produce antibodies, and cytotoxic response to virus-infected cells. Bats are able to suppress the most highly pathogenic viruses found in mammals (e.g., SARS, Ebola, Rabies, and Nipah) with little to no clinical symptoms or pathology acting as the main reservoir. Yet after 100 years of anatomical study little is known about T cell development, abundance, expression, or T-cell receptors (TCRs) repertoire within bats. Studies of bat T cell development and responses in bats have largely been understudied due to lack of immunological reagents such as antibodies specific for bats. In this resubmission, our research team has provided preliminary data using x-ray computed tomography, histology, and immunohistochemistry that bats have thymus with T cells present. We also provide evidence of age related thymus involution within adult big brown bats (Eptesicus fuscus). In our proposal, we will use museum voucher specimens and collect wild bats to further develop methods for structural and molecular approaches to study lymphoid organs and T cell development. Our team has decades of experience in mammalogy, viral-host interaction, adaptive immune system sequencing (VDJseq), and viral immunology. We will provide ultrastructural determination of the bat’s thymus, spleen, lymph ducts, and bone marrow that will include development of antibodies for flow cytometry/FACS or mRNA based in situ hybridization flow cytometry (Flow-FISH), single molecule fluorescence mRNA in situ hybridization (mRNA-smFISH) and immunohistochemistry (which we have preliminary data) that will elucidate the lymphoid organs of T cell development (Aim 1). In Aim 2, we will assess T cell development in bat primary and secondary lymphoid organs across developmental age (juveniles, subadults, and adults) and examine sexual dimorphism, using bulk organ RNAseq, single cell RNAseq, and RT-ddPCR. Using VDJseq/TCRseq we will measure the TCR repertoire diversity across lymphoid tissues and blood (Aim 2). In Aim 3, we will access and link thymic involution to the susceptibility of bats to pathogenic viruses. Our proposal and team is uniquely posed to provide a new path towards unraveling the ‘black box’ of bat T cell adaptive immune responses. This is foundational work that will enable further immunological study in bats and other small mammals but provide a groundwork to new immunotherapies, vaccines, antivirals, or anti-inflammatory drugs.",,2026,UNIVERSITY OF NORTH CAROLINA CHARLOTTE,424816,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P21458,1U01AI168287-01A1,Solving Opportunities for Spillover (SOS): Frequency and Mechanisms of Cross-species Transmission of Henipaviruses in Bangladesh,"Abstract Until and unless we better understand and prevent spillovers of bat-borne viruses into intermediate hosts and humans, we will be severely limited in our ability to stop pandemics. Henipaviruses are bat-borne, RNA viruses that spillover through this route. Nearly half of all reported human henipavirus infections have been associated with contact with sick domesticated animals, though our understanding of drivers of henipavirus spillovers and specific transmission pathways remains severely limited. Building on preliminary data about bat, domesticated animal and human infections, this multidisciplinary study integrates epidemiology, ecology, and anthropology to identify spillover pathways for henipaviruses into domesticated animals in Bangladesh and the risk they pose to human health. Our first aim is to identify drivers of henipavirus spillovers into domesticated animals in Faridpur, Bangladesh. We will use multiplex pan-henipavirus assays to identify infections in Pteropus medius bats and domesticated animals living nearby this roost through cross-sectional and prospective studies. Combined with intensive studies of bat-domesticated animal interactions and weather data, we will build statistical models to identify the relative contribution of each of these factors. Our second aim is to describe which henipaviruses are being transmitted from bats to domesticated animals. Serologic studies of animals in Bangladesh show that they are frequently infected with non-Nipah henipaviruses. Through surveillance for and sampling of sick domesticated animals, we will describe the specific viruses that spillover from bats in Faridpur. Our third aim is to determine the risk of henipavirus transmission from domesticated animals to humans. We hypothesize that undetected henipavirus spillovers in humans are occurring through contact with sick domesticated animals and will conduct cross-sectional and prospective serosurveys of humans who have close contact with sick animals in Faridpur. We remain ignorant about henipavirus spillovers through intermediate hosts â€Â"" including the specific viruses spilling over, the frequency and distribution of spillovers, and the pathways of transmission â€Â"" at our own peril. The knowledge gained from this study will be immediately applicable to human and animal health programs in Bangladesh and other countries where henipaviruses circulate in bats. By learning about which henipaviruses infect humans, and how they are infected, we can advise public health surveillance programs on how to optimize detection and epidemiologic investigation of cases across Bangladesh. Our investigations about spillovers in Faridpur can also be scaled- up to other areas of Bangladesh and countries where henipaviruses circulate in bats so that we can truly begin to appreciate the scale of henipavirus spillovers in the global landscape.",,2027,Johns Hopkins University,691098,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2023 +P21459,1U01AI173348-01,"Structure, function, and antigenicity of emerging henipavirus surface glycoproteins","Abstract Henipavirus (HNV) genus, named after the first two identified members, Hendra virus (HeV) and Nipah virus (NiV), is a group of expanding zoonotic viruses that have caused repeated outbreaks with case fatality rate reaching 75%. The exceptional broad species tropism and various transmission routes make HNV a risk of potential future pandemics. Both HeV and NiV have been categorized as Biological Safety Level-4 (BSL-4) transboundary agents, and NIAID Category C Priority Pathogens. There are six emerging HNVs reported in recent years, showing limited antigenic cross-reactivity with NiV and HeV. Glycoproteins F and G are the two only spikes on the HNV surface, which coordinate the viral entry process via G glycoprotein-mediated receptor attachment followed by the F glycoprotein-mediated membrane fusion between virus and host cell. Both G and F proteins are the targets of HNV-neutralizing antibodies. Vaccine and monoclonal antibody (mAb) countermeasure development focusing on these two HNV glycoproteins are now of critical and urgent importance to prepare for potential HNV spillover events. The ectodomain of HNV G glycoprotein is a homo- tetramer with each protomer composed of a globular head and a stalk region. The metastable tetrameric conformation has restricted the previous structural characterization of G protein to the monomeric head only, which is a major obstacle for a comprehensive understanding of the G protein-mediated mechanisms of HNV entry and antibody recognition. HNV F glycoprotein trimer transits from the prefusion to the post-fusion conformation during viral entry process. The metastable prefusion conformation can be preferably recognized by neutralizing antibodies, whereby a promising target for vaccine design and therapeutic development. While the glycoproteins of both HeV and NiV have been extensively studied, the glycoproteins of the emerging HNVs, which are genetically and antigenically distinct from the two prototypic HNVs, also extremely diverse among themselves, have not been well investigated. We have used rational designs to created soluble, stabilized, oligomeric glycoprotein ectodomain constructs from several emerging HNVs, including two phylogenically distant bat-borne HNVs, CedPV and AngV, to facilitate structural, functional and antigenicity characterization. We propose to use structural and structure-based functional analyses of these glycoproteins to assist delineation of the function of HNV glycoprotein-mediated entry. We will also define the antigenicity of these HNV glycoproteins with neutralizing antibodies, including conventional murine antibodies and camelid single-domain antibodies, to investigate their neutralization epitopes and mechanisms structurally and functionally. The combined antigenicity results will render a comprehensive definition of sites of vulnerability on both G and F glycoproteins of the emerging HNVs. Collectively, findings derived from this project will provide insights to HNV entry mechanism, as well as inform future work on designing envelope glycoprotein-based vaccine and immunotherapeutic against emerging HNVs.",,2028,Ohio State University,597757,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P21460,5DP2AI171120-02,Crossing scales to predict and prevent bat virus zoonoses in a Madagascar ecosystem,"The wide-reaching impacts of the COVID-19 pandemic highlight the extreme threat posed by the cross-species emergence of zoonotic pathogens. Bats (order: Chiroptera) are the natural reservoir hosts for the majority of the world’s most virulent zoonotic viruses, including Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS, MERS, and now SARS-CoV-2 coronaviruses. Remarkably, bats exhibit little demonstrable disease upon infection with viruses that cause extreme pathology in other mammals, likely in part due to their unique anti-inflammatory molecular adaptations, which are thought to have evolved to mitigate the accumulation of physiological damage accrued during flight. Surprisingly, isolated island bat communities around the world support the endemic circulation of numerous viruses in populations below the critical community size required for persistence of related pathogens in other hosts. Since cross-species spillover of several bat-borne viruses bears a distinctive seasonal signature, coincident with the timing of reproductive and nutritional stress for the bat hosts in question, disentangling the mechanisms governing the transmission, circulation, and persistence of these viruses in wild bat populations is of critical public health interest. In part with the research initiatives proposed here, we will use molecular and serological tools to develop a longitudinal time series of immunological and infection data for henipaviruses and coronaviruses circulating in wild fruit bats in Madagascar, leveraging samples collected in our longterm wildlife surveillance effort. Bats are widely consumed as a source of human food in Madagascar, and preliminary data from our research group demonstrates serological signatures of prior human exposure to these zoonotic viruses across the island. We propose to fit disparate dynamical models to the resulting population-level data in order to distinguish mechanisms underpinning seasonal viral shedding pulses and concomitant transmission in these bat hosts. In addition to population-level studies, we will also construct within-host models of viral control in a single bat immune system, which we will fit to experimental infection data from Betacoronavirus-challenged bats in the laboratory, with the aim of deciphering the mechanisms which motivate viral shedding. Our project aims to simultaneously develop molecular tools of bat cell lines and viruses with which to support within-host studies in our own Madagascar system. Finally, we will build on population-level and within-host studies to model and implement a vaccine intervention designed to eradicate circulating henipavirus from a test-population of Madagascar fruit bats. Broadly, our project aims to use a uniquely integrative combination of field, molecular, and modeling tools to enable the prediction and prevention of bat virus spillover events before they occur.",,2027,University Of Chicago,461856,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Animal source and routes of transmission,2022 +P21461,1R21AI169536-01A1,Mechanisms of antiviral immunity and tolerance in the intestinal epithelium of Jamaican Fruit Bats,"Summary The gastrointestinal (GI) tract is a major target organ for viral infection in bats, but infections rarely cause typical symptoms of viral enteritis such as diarrhea. The long-term goal of our project is to understand the specific innate immune response mechanisms of the intestinal epithelium that enable bats to sustain viral infection without experiencing cytopathic effects and intestinal barrier dysfunction. We hypothesize that protective type I and type III interferon (IFN) responses in Jamaican Fruit Bats (Artibeus jamaicensis, JFBs) enable persistent, asymptomatic viral infection of the gastrointestinal epithelium. To test our hypothesis, we will utilize a novel in vitro model of the JFB intestine, 3-D enteroids, which are complex long-term cultures of primary intestinal epithelial cells generated from adult tissue-derived stem cells. Responses in the gut epithelium of JFBs will be compared to those induced in human enteroids. In Aim 1, we will define type I/III IFN responses of JFB enteroids to viral infection. In Aim 2, we will determine to what extent type I/III IFNs impact viral replication and barrier function in the gastrointestinal epithelium of JFBs. We will analyze intestinal epithelial cell responses to three single-stranded RNA viruses that can infect JFB cells: H18N11 influenza virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Cedar virus, a non-pathogenic henipavirus. Specifically, we will analyze the kinetics of viral replication and type I/III IFN activation in the enteroids and will also perform a comprehensive proteomics analysis of virus-infected intestinal epithelial cells. To assess the role of virus-induced type I/III IFNs for gastrointestinal epithelial pathology, IFN signaling will be induced or inhibited, and the impact on enteroid susceptibility to viral infection will be analyzed. We also will measure epithelial cell viability, barrier and repair functions that are commonly disrupted during viral enteritis. Our project is technologically innovative, because we will, for the first time, analyze viral infection in enteroid cultures derived from JFBs and because we also will perform a complete proteome analysis of the JFB intestinal epithelium. The proposed work is conceptually innovative, because it will define how virus-induced type I/III IFNs impact intestinal epithelial function and integrity. Our proposed work is significant, because it will provide novel insights in the epithelial cell-intrinsic innate immune mechanisms involved in asymptomatic infection of the bat intestine with viral pathogens, which has important implications for potential pathogen spillover events.",,2025,Montana State University - Bozeman,214575,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Paramyxovirdiae | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Nipah and henipaviral disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2023 +P21462,1R24AI165424-01A1,Establishment of a Bat Resource for Infectious Disease Research,"Project Summary / Abstract Bats are reservoirs, or suspected reservoirs, of many zoonotic viruses, including SARS, SARS2 and MERS coronaviruses, Nipah and Hendra viruses, and Ebola and Marburg viruses. Little is known about how these viruses circulate in their bat reservoirs, principally because of a lack of bat colonies that can be used for the development of experimental infection models. To address this deficiency, we will capture horseshoe bats and Indian flying foxes, respective reservoir hosts of Nipah virus and SARS-related coronaviruses, in Bangladesh where they will be quarantined and provided veterinary care as they adapt to captivity. Bats will be shipped to CSU to establish the breeding colonies as a resource for investigators who study these viruses. We will generate primary cell cultures and immortalized cell lines from various tissues and freeze live bone marrow that will be useful for studying how these viruses infect bat cells, and how the viruses may modulate the innate immune responses. Recombinant cytokines will also be produced for the research community, including those for generating macrophages and dendritic cells (GM-CSF, Flt3L), T cells (IL-2) and for in vivo modulation of the adaptive immune response (IFN, IL-4). Moreover, we will generate monoclonal antibodies for use in cytokine detection assays and flow cytometry of immune cell subsets and in vivo neutralization. Finally, we will perform experimental infection studies of Nipah virus, SARS-CoV-2 and the SARS-related coronavirus, RaTG13, to study the infection kinetics, virus distribution and transcriptomic, proteomic and metabolomic profiles of bats during infection, and escalation and resolution of the immune response. Tissues, cells and sera from naïve and infected bats will be archived in a biobank that will be made available to the research community. The establishment of this resource will lead to a better understanding of how bats host highly pathogenic viruses without disease and may shed light on events that increase spillover risks to humans. In turn, this information could lead to development of mitigation strategies to prevent future virus spillover and uncover new strategies for therapeutic treatment of coronavirus and Nipah virus diseases.",,2028,Colorado State University,1694054,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Paramyxovirdiae,,,,,,,,,COVID-19 | Nipah and henipaviral disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Diagnostics | Pathogen morphology, shedding & natural history | Disease models | Animal source and routes of transmission",2023 +P21463,5U01AI153420-04,Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks,"Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.",,2025,"ECOHEALTH ALLIANCE, INC.",535284,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Disease models | Animal source and routes of transmission,2020 +P21464,5R21AI169481-02,SHINING A LIGHT ON BAT CELLULAR IMMUNITY FOLLOWING VIRUS INFECTION,"Project summary/abstract Bats are important reservoir hosts for a variety of viruses, several of which are associated with fatality rates as high as 90% among diagnosed human cases. This includes the highly pathogenic henipaviruses, of which Hendra virus (HeV) emerged in Australia and Nipah virus (NiV) in South-east Asia via horse and pig intermediate hosts respectively. The henipaviruses have been shown to be transmitted from Pteropus bats, with the Australian black flying fox (Pteropus alecto) confirmed as a reservoir for HeV (1, 2). As with other viral infections in bats, natural or experimental infection of bats with HeV causes no clinical signs of disease despite shedding of virus. The antiviral immune response of P. alecto is among the most well studied of all bat species, with novel immune mechanisms already discovered including the constitutive expression of interferon alpha discovered by our team (3). These characteristics make the P. alecto â€Â"" HeV model uniquely suited to answering the questions we propose in this project. Despite the increasing emergence of zoonotic viruses from bats, studies of bat immunology remain in their infancy and few studies have examined the adaptive immune responses of any bat species. Understanding the antiviral responses in bats is crucial if we are to predict and prevent virus spillover from bats to other susceptible species, understand disease pathogenesis in other mammals and uncover new therapeutics and vaccines to treat these diseases in humans and other animals. In this study, we will characterise the innate and adaptive immune response of experimentally infected bats to HeV to obtain detailed insights into how bats control viral infection. The cell mediated immune response of bats will be dissected using functional assays to determine the subsets of cells activated during an active infection and explore global gene and protein expression to characterise the innate and adaptive immune response of infected bats. The use of innovative approaches to identify MHC bound HeV peptides in infected bats, building on previous bat immunopeptidomics studies, will provide new insights into peptide presentation during infection. Few studies have comprehensively studied the immune response of bats during infection, and none have examined the functional activation of the cell mediated immune response. Comparison with infected ferrets will allow us to directly compare mechanisms responsible for innocuous (bats) compared to fatal (ferrets) HeV infection. Expected outcomes include understanding the basic biology of antiviral responses in bats and the development of new tools to monitor bat immunity to HeV and related viruses. The Australian Centre for Disease Preparedness and Monash University are uniquely suited for performing the work outlined in this proposal with a strong track record of working together on bat immunology. The team has access to high containment facilities and expertise to perform animal infections with dangerous pathogens combined with access to protein chemistry facilities and expertise in generating tetramer reagents.",,2024,COMMONWEALTH SCIENTIFIC & INDUST RES ORG,146098,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Hendra virus infection,National Institutes of Health (NIH),United States of America,Americas,Western Pacific,,,,,Australia,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology,2022 +P21465,5U01AI151801-04,West African Center for Emerging Infectious Diseases,"Arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV) and Zika (ZIKV), as well as rodent- and bat-borne viruses such as Lassa fever and probably Ebola, are among the most important causes of emerging infectious diseases, and many circulate enzootically in W. Africa. The mechanisms whereby these and other zoonotic African viruses emerge and spread remain obscure, along with the understanding of their disease burden and varied clinical outcomes. The West African Center for Emerging Infectious Diseases will address these critical gaps through field studies of enzootic transmission, and clinical studies of human exposure and disease outcome. Our surveillance of humans, and wild animals, including bats (probable hosts of filoviruses, coronaviruses and henipaviruses), and mosquitoes/ticks, will likely identify new emerging viral pathogens. Further, the infrastructure and local expertise developed through these projects in Senegal, Sierra Leone and Nigeria, along with biosafety/biosecurity training and improved diagnostics, will also prepare the region for future outbreaks of emerging viral and other infectious diseases. The Center’s aims are to: 1. Study zoonotic arboviruses in Senegal, Sierra Leone and Nigeria, including identification and characterization of critical reservoir and amplification hosts, enzootic and epidemic vectors, temporal patterns of enzootic and epidemic circulation, levels of human exposure, immune responses and disease outcomes. The emphasis will be on the 4 “urban” (human amplified) arboviruses: CHIKV, DENV, YFV and ZIKV, but other known and possibly unknown viruses will also be studied. Risk maps will be generated. 2. In Sierra Leone and Nigeria, study the circulation among rodent hosts and infections of humans by Lassa virus, including identification of viral determinants of hemorrhagic disease severity and sequelae outcomes, and determination of the mechanisms of strain virulence variation. Risk maps will also be generated. 3. Perform surveillance in bats to identify potential sources of Ebola virus in W. Africa as well as other known or unknown zoonotic pathogens, including coronaviruses and henipaviruses that may be causing human disease, and which may explain the origins of emerging pathogens such as Nipah and MERS coronavirus. 4. Establish biocontainment and biosecurity training programs, advanced yet affordable viral genomics capabilities, and comprehensive diagnostics to support these aims as well as to improve research infrastructure and future outbreak responses in W. Africa. Our results will increase the mechanistic understanding of zoonotic viral maintenance and emergence, etiologies of febrile and hemorrhagic diseases, diverse disease outcomes, and risks for local and international spread. Novel viruses with emergence potential will likely be discovered, and existing collaborations between the Univ. of TX Medical Branch and its partners in Senegal, Sierra Leone, and Nigeria, as well as research infrastructure, will be strengthened to prepare for and respond quickly and effectively to future outbreaks.",,2025,University Of Texas Med Br Galveston,1542169,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Arenaviridae | Coronavirus | Filoviridae | Flaviviridae | Paramyxovirdiae,,,,,,,,,Lassa fever | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Zika virus disease | Nipah and henipaviral disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Clinical characterisation and management,Animal source and routes of transmission | Vector biology | Disease transmission dynamics | Disease pathogenesis,2020 +P21466,1R01AI175362-01,Broad spectrum inhibitors of paramyxovirus envelope proteins,"Abstract Human parainfluenza viruses (HPIV) cause a significant portion of childhood croup, bronchiolitis and pneumonia in the U.S. and worldwide, yet no effective drugs or vaccines are available. For the lethal Nipah (NiV) and Hendra (HeV) viruses, in the face of human-to-human transmission of NiV, there is risk for global spread as well as accidental or deliberate exposure. Despite the existence of antibody preparations for passive immunoprophylaxis, there is no feasible approach to prevent or treat the human disease. These viruses serve as prototypes for emerging paramyxoviruses. With this application we build on recent breakthroughs that have led to a new broad-spectrum antiviral strategy based on inhibiting fusion during viral entry. We combine structure-based optimization of fusion inhibitory lipopeptides, backbone modification via partial replacement of α-amino acid residues with unnatural β-amino acid residues to enhance half-life, and addition of lipid components to enhance antiviral efficacy. Using virologic, ex vivo, and in vivo experiments we will develop powerful novel HPIV3/NiV/HeV fusion inhibitors that can be administered by inhalation. Validation of our strategies with circulating respiratory viruses and clinical NiV virus strains in vitro and in vivo will lead us to antiviral agents that are effective and practical in the clinical setting. Aim 1. Targeting the paramyxovirus fusion complex: Evaluate entry inhibitor approaches in vitro. We will develop fusion-inhibitory lipopeptides, combining conventional peptide design with backbone- modification and membrane targeting to optimize broad fusion inhibition activity for NiV, HeV, HPIV, and optimize potency, protease resistance, and tissue targeting of lead lipopeptides. We will evaluate antiviral activity and potential for antiviral resistance in authentic ex vivo models. Human airway and brain models will be employed to elicit resistant viruses in ex vivo evolution experiments, to study the molecular bases for antiviral activity and potential for resistance to lead peptides. Aim 2. Pharmacokinetics, biodistribution and efficacy of formulated lead antivirals in vivo. We will assess the biodistribution and immunogenicity, acute toxicity, and PK/PD via nasal or inhalation delivery of lead candidate series in small animal models, and evaluate efficacy of lead peptides for NiV/HeV in golden hamsters and for HPIV in cotton rats. An efficacy study for the NiV lead will be conducted in African green monkeys. We propose that peptide backbone modification and membrane targeting strategies will generate broad anti- paramyxovirus agents that can be delivered via inhalation with unprecedented efficacy and pharmacokinetic properties.",,2027,Columbia University Health Sciences,848745,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21467,5R01AI160226-03,Preclinical development of a vaccine for Nipah virus,"PROJECT SUMMARY/ABSTRACT Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is also categorized as a Category C priority pathogen by several US Government agencies because of the concern for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018 List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ÃŽÂ""G) vesicular stomatitis virus (rVSVÃŽÂ""G) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses. In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when used as single injection vaccines. This new data is critically important in the context of containing outbreaks as the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that works rapidly with a single administration. Development of a replication restricted platform that provides improved safety without compromising efficacy is a highly significant advancement and can be applied to other viruses with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV (rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank (RVB), a manufacturing process, and conduct of GLP-safety toxicology.",,2026,University Of Texas Med Br Galveston,1159045,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21468,5R21AI164401-02,Therapeutic efficacy of favipiravir against henipavirus infections,"ABSTRACT Nipah and Hendra viruses are recently emerged bat-borne paramyxoviruses (genus Henipavirus) causing severe encephalitis and respiratory disease in humans with fatality rates ranging from 40-75%. Despite the severe pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved for use in humans. Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe. Previously, broad-spectrum antiviral activity of favipiravir has been demonstrated against a large number of RNA viruses, including members of the Paramyxoviridae, Filoviridae, Arenaviridae, and Bunyaviridae families. With the ongoing COVID-19 pandemic, favipiravir has also been discussed as a potential antiviral drug for treatment of mild to moderate symptomatic SARS-CoV-2-infected patients and is currently tested in several clinical trials. We were able to demonstrate that favipiravir has potent antiviral activity against henipaviruses in cell culture with EC50's in the low micromolar range. Furthermore, we could show that treatment with favipiravir resulted in full protection of Nipah virus-infected hamsters, suggesting that favipiravir should be further evaluated as an antiviral treatment option for henipavirus infections. The overall goal of this application is to develop antiviral treatment options for infections caused by henipaviruses. Our hypothesis is that favipiravir will demonstrate therapeutic antiviral efficacy against all human pathogenic Nipah virus strains and Hendra virus in a disease-relevant and widely accepted small animal model, will be efficacious in a post-exposure setting, and interrupt transmission. To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Optimize the therapeutic efficacy of favipiravir against henipavirus infection in the Syrian hamster model; and (2) Evaluate if favipiravir can evoke extinction of Nipah virus through lethal mutagenesis. The proposed studies will provide fundamental information for the further development of favipiravir as a broad-spectrum antiviral, and ultimately lead to the development of countermeasures against henipavirus infections.",,2024,University Of Texas Med Br Galveston,200000,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21470,5R41AI157095-02,Furopyrimidines as novel inhibitors of henipaviruses,"The emergence and reemergence of pathogenic viruses represent continuous infectious disease threats to public health. Among these, the paramyxoviruses, which include many important human and animal pathogens, also include two excellent examples of emerged, zoonotic viral pathogens of importance: the henipaviruses; Hendra virus (HeV) and Nipah virus (NiV). HeV and NiV have a uniquely broad host tropism capable of infecting at least 18 animal species across 6 orders of mammals. HeV and NiV can also cause a systemic and often fatal respiratory and/or neurological disease in 11 mammalian species including humans. These henipaviruses remain significant biothreats to humans and economically important livestock in Australia and throughout South East Asia. In addition, there are no vaccines or antivirals approved for human use. Thus new treatment options are urgently needed. This application defines a plan to develop potent, small molecule inhibitors, which inhibit henipavirus replication. We have identified compounds that inhibit replication of these viruses, with IC50 values in the nanomolar range. In this application, we propose three specific aims: (1) To optimize the lead (and backup) scaffold and select developmental candidates; (2) Develop the SAR in the henipavirus infectious assay and further investigate the mechanism of action (MOA) of the replication inhibitors; and (3) Select henipavirus inhibitors with in vitro ADME properties suitable for whole animal testing in an infectious animal model.",,2023,"CHICAGO BIOSOLUTIONS, INC.",299667,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21471,5F31AI152422-02,Roles of Pteropine Bat and Human TRIMs in Regulating Henipavirus Infection,"Project Summary Bat species are the natural hosts of several emerging and re-emerging viruses including henipaviruses (HNVs). Although infection with these viruses causes high case fatality rates in humans, bats appear tolerant. Old World fruit bats in the family Pteropodidae are the natural reservoirs of HNVs, including Henda (HeV) and Nipah (NiV). HNV-pteropine bat ecological interactions are well-studied, but the mechanisms underlying the limited immunopathology in pteropine bats following HNV infection are unknown. During HNV infection in humans, the antiviral type I interferon (IFN-I) pathways are suppressed in part through the antagonism of tripartite motif proteins (TRIMs). TRIMs are involved in modulating antiviral immune responses including IFN-I production and signaling pathways. Some members of the TRIM E3 ubiquitin ligase family stimulate the IFN-I and pro-inflammatory antiviral pathways to promote viral clearance while others antagonize these pathways to limit immune-associated pathology. We have generated preliminary data that demonstrates NiV activates the IFN-I signaling pathway human cells late in infection, but IFN-I signaling remains antagonized efficiently in bat cells throughout the duration of infection. Based on this observation, we predict that bats have evolved to express a TRIM in response to NiV infection that negatively regulates the cytoplasmic RNA recognition pathway to prevent the cytopathic effects of innate immune signaling. Previously, we described the role of NiV matrix protein (NiV-M) in the degradation of human TRIM6, which inhibits TRIM6-mediated activation of IKKε- dependent IFN-I production and signaling. We found that bat TRIM6 interacts with NiV-M, but bat TRIM6 resists NiV-M mediated degradation. Due to this species-specific difference, we are interested in identifying the mechanisms that confer degradation resistance to bat TRIM6 and understanding the roles of TRIM6 during NiV infection. In this proposal, we hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human, cells that promotes tolerance, and that species-specific differences in NiV-M-mediated TRIM6 degradation influences the course of infection. We will interrogate our hypothesis through two specific aims: (1) to identify pteropine and human TRIM orthologs differentially expressed after NiV infection and determine their roles in innate immune regulation and (2) To elucidate the mechanistic roles of human and bat TRIM6 in regulating NiV infection. Overall, the results of the proposed study will promote our understanding of the molecular regulation of pteropine bat IFN-I pathways and potentially identify factors that facilitate bats’ tolerance to HNVs. Elucidating the mechanisms that promote tolerance to HNV may serve as a basis for the development of human therapeutics.",,2022,University Of Texas Med Br Galveston,12549,Animals | Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Vector biology,2021 +P21473,5F31AI154739-03,Elucidating the molecular determinants of Henipavirus envelope-antibody and envelope-receptor interactions on viral entry,"PROJECT SUMMARY: The identification of new Henipaviruses (HNVs) in Africa, China and Australia lend way to concerns about the risk of possible spillover events. Yet, there are no FDA approved therapeutics and the role of receptor usage on pathogenicity is still undetermined. Within this proposal, we aim to leverage our extensive preliminary results to further our understanding of the molecular determinants of envelope-antibody and envelope-receptor interactions on viral neutralization and viral pathogenicity. In recent work, we have identified an immune- accessible region on the NiV and HeV fusion glycoprotein that is targeted by several antibodies. Experiments proposed in Aim 1 will elucidate a mechanism for how these antibodies neutralize HNVs and will characterize novel antibodies against the divergent GhV fusion glycoprotein by utilizing a rapid, directed-evolution platform to identify escape mutants. Additionally, we have performed structure-guided mutagenesis to better understand HNV receptor binding protein and receptor interactions. The experiments directly proposed in Aim 2 will further characterize these mutants and assess the ability to confer use of this receptor to other HNVs using viruses. The work proposed here will ultimately support the development of HNV therapeutics and the understanding of the contributions of receptor usage on HNV pathogenicity.",,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,45152,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21474,1DP2AI171120-01,Crossing scales to predict and prevent bat virus zoonoses in a Madagascar ecosystem,"The wide-reaching impacts of the COVID-19 pandemic highlight the extreme threat posed by the cross-species emergence of zoonotic pathogens. Bats (order: Chiroptera) are the natural reservoir hosts for the majority of the world’s most virulent zoonotic viruses, including Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS, MERS, and now SARS-CoV-2 coronaviruses. Remarkably, bats exhibit little demonstrable disease upon infection with viruses that cause extreme pathology in other mammals, likely in part due to their unique anti-inflammatory molecular adaptations, which are thought to have evolved to mitigate the accumulation of physiological damage accrued during flight. Surprisingly, isolated island bat communities around the world support the endemic circulation of numerous viruses in populations below the critical community size required for persistence of related pathogens in other hosts. Since cross-species spillover of several bat-borne viruses bears a distinctive seasonal signature, coincident with the timing of reproductive and nutritional stress for the bat hosts in question, disentangling the mechanisms governing the transmission, circulation, and persistence of these viruses in wild bat populations is of critical public health interest. In part with the research initiatives proposed here, we will use molecular and serological tools to develop a longitudinal time series of immunological and infection data for henipaviruses and coronaviruses circulating in wild fruit bats in Madagascar, leveraging samples collected in our longterm wildlife surveillance effort. Bats are widely consumed as a source of human food in Madagascar, and preliminary data from our research group demonstrates serological signatures of prior human exposure to these zoonotic viruses across the island. We propose to fit disparate dynamical models to the resulting population-level data in order to distinguish mechanisms underpinning seasonal viral shedding pulses and concomitant transmission in these bat hosts. In addition to population-level studies, we will also construct within-host models of viral control in a single bat immune system, which we will fit to experimental infection data from Betacoronavirus-challenged bats in the laboratory, with the aim of deciphering the mechanisms which motivate viral shedding. Our project aims to simultaneously develop molecular tools of bat cell lines and viruses with which to support within-host studies in our own Madagascar system. Finally, we will build on population-level and within-host studies to model and implement a vaccine intervention designed to eradicate circulating henipavirus from a test-population of Madagascar fruit bats. Broadly, our project aims to use a uniquely integrative combination of field, molecular, and modeling tools to enable the prediction and prevention of bat virus spillover events before they occur.",,2027,University Of Chicago,460576,Animals | Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Disease models | Animal source and routes of transmission | Vector control strategies | Vector biology",2022 +P21475,5U01AI153420-03,Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks,"Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.",,2025,"ECOHEALTH ALLIANCE, INC.",600404,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease models | Animal source and routes of transmission | Vector biology | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis",2020 +P21476,1R21AI169481-01,SHINING A LIGHT ON BAT CELLULAR IMMUNITY FOLLOWING VIRUS INFECTION,"Project summary/abstract Bats are important reservoir hosts for a variety of viruses, several of which are associated with fatality rates as high as 90% among diagnosed human cases. This includes the highly pathogenic henipaviruses, of which Hendra virus (HeV) emerged in Australia and Nipah virus (NiV) in South-east Asia via horse and pig intermediate hosts respectively. The henipaviruses have been shown to be transmitted from Pteropus bats, with the Australian black flying fox (Pteropus alecto) confirmed as a reservoir for HeV (1, 2). As with other viral infections in bats, natural or experimental infection of bats with HeV causes no clinical signs of disease despite shedding of virus. The antiviral immune response of P. alecto is among the most well studied of all bat species, with novel immune mechanisms already discovered including the constitutive expression of interferon alpha discovered by our team (3). These characteristics make the P. alecto â€Â"" HeV model uniquely suited to answering the questions we propose in this project. Despite the increasing emergence of zoonotic viruses from bats, studies of bat immunology remain in their infancy and few studies have examined the adaptive immune responses of any bat species. Understanding the antiviral responses in bats is crucial if we are to predict and prevent virus spillover from bats to other susceptible species, understand disease pathogenesis in other mammals and uncover new therapeutics and vaccines to treat these diseases in humans and other animals. In this study, we will characterise the innate and adaptive immune response of experimentally infected bats to HeV to obtain detailed insights into how bats control viral infection. The cell mediated immune response of bats will be dissected using functional assays to determine the subsets of cells activated during an active infection and explore global gene and protein expression to characterise the innate and adaptive immune response of infected bats. The use of innovative approaches to identify MHC bound HeV peptides in infected bats, building on previous bat immunopeptidomics studies, will provide new insights into peptide presentation during infection. Few studies have comprehensively studied the immune response of bats during infection, and none have examined the functional activation of the cell mediated immune response. Comparison with infected ferrets will allow us to directly compare mechanisms responsible for innocuous (bats) compared to fatal (ferrets) HeV infection. Expected outcomes include understanding the basic biology of antiviral responses in bats and the development of new tools to monitor bat immunity to HeV and related viruses. The Australian Centre for Disease Preparedness and Monash University are uniquely suited for performing the work outlined in this proposal with a strong track record of working together on bat immunology. The team has access to high containment facilities and expertise to perform animal infections with dangerous pathogens combined with access to protein chemistry facilities and expertise in generating tetramer reagents.",,2024,COMMONWEALTH SCIENTIFIC & INDUST RES ORG,150190,Animals | Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Western Pacific,,,,,Australia,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Animal source and routes of transmission,2022 +P21477,5U01AI151801-03,West African Center for Emerging Infectious Diseases,"Arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV) and Zika (ZIKV), as well as rodent- and bat-borne viruses such as Lassa fever and probably Ebola, are among the most important causes of emerging infectious diseases, and many circulate enzootically in W. Africa. The mechanisms whereby these and other zoonotic African viruses emerge and spread remain obscure, along with the understanding of their disease burden and varied clinical outcomes. The West African Center for Emerging Infectious Diseases will address these critical gaps through field studies of enzootic transmission, and clinical studies of human exposure and disease outcome. Our surveillance of humans, and wild animals, including bats (probable hosts of filoviruses, coronaviruses and henipaviruses), and mosquitoes/ticks, will likely identify new emerging viral pathogens. Further, the infrastructure and local expertise developed through these projects in Senegal, Sierra Leone and Nigeria, along with biosafety/biosecurity training and improved diagnostics, will also prepare the region for future outbreaks of emerging viral and other infectious diseases. The Center’s aims are to: 1. Study zoonotic arboviruses in Senegal, Sierra Leone and Nigeria, including identification and characterization of critical reservoir and amplification hosts, enzootic and epidemic vectors, temporal patterns of enzootic and epidemic circulation, levels of human exposure, immune responses and disease outcomes. The emphasis will be on the 4 urban (human amplified) arboviruses: CHIKV, DENV, YFV and ZIKV, but other known and possibly unknown viruses will also be studied. Risk maps will be generated. 2. In Sierra Leone and Nigeria, study the circulation among rodent hosts and infections of humans by Lassa virus, including identification of viral determinants of hemorrhagic disease severity and sequelae outcomes, and determination of the mechanisms of strain virulence variation. Risk maps will also be generated. 3. Perform surveillance in bats to identify potential sources of Ebola virus in W. Africa as well as other known or unknown zoonotic pathogens, including coronaviruses and henipaviruses that may be causing human disease, and which may explain the origins of emerging pathogens such as Nipah and MERS coronavirus. 4. Establish biocontainment and biosecurity training programs, advanced yet affordable viral genomics capabilities, and comprehensive diagnostics to support these aims as well as to improve research infrastructure and future outbreak responses in W. Africa. Our results will increase the mechanistic understanding of zoonotic viral maintenance and emergence, etiologies of febrile and hemorrhagic diseases, diverse disease outcomes, and risks for local and international spread. Novel viruses with emergence potential will likely be discovered, and existing collaborations between the Univ. of TX Medical Branch and its partners in Senegal, Sierra Leone, and Nigeria, as well as research infrastructure, will be strengthened to prepare for and respond quickly and effectively to future outbreaks.",,2025,University Of Texas Med Br Galveston,1543607,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Arenaviridae | Filoviridae | Flaviviridae | Paramyxovirdiae,,,,,,,,,Lassa fever | Ebola virus disease | Zika virus disease | Nipah and henipaviral disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Vector biology | Disease susceptibility",2020 +P21478,5R01AI160226-02,Preclinical development of a vaccine for Nipah virus,"PROJECT SUMMARY/ABSTRACT Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is also categorized as a Category C priority pathogen by several US Government agencies because of the concern for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018 List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ÃŽÂ""G) vesicular stomatitis virus (rVSVÃŽÂ""G) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses. In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when used as single injection vaccines. This new data is critically important in the context of containing outbreaks as the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that works rapidly with a single administration. Development of a replication restricted platform that provides improved safety without compromising efficacy is a highly significant advancement and can be applied to other viruses with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV (rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank (RVB), a manufacturing process, and conduct of GLP-safety toxicology.",,2026,University Of Texas Med Br Galveston,1179782,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21479,1R21AI164401-01,Therapeutic efficacy of favipiravir against henipavirus infections,"ABSTRACT Nipah and Hendra viruses are recently emerged bat-borne paramyxoviruses (genus Henipavirus) causing severe encephalitis and respiratory disease in humans with fatality rates ranging from 40-75%. Despite the severe pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved for use in humans. Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe. Previously, broad-spectrum antiviral activity of favipiravir has been demonstrated against a large number of RNA viruses, including members of the Paramyxoviridae, Filoviridae, Arenaviridae, and Bunyaviridae families. With the ongoing COVID-19 pandemic, favipiravir has also been discussed as a potential antiviral drug for treatment of mild to moderate symptomatic SARS-CoV-2-infected patients and is currently tested in several clinical trials. We were able to demonstrate that favipiravir has potent antiviral activity against henipaviruses in cell culture with EC50's in the low micromolar range. Furthermore, we could show that treatment with favipiravir resulted in full protection of Nipah virus-infected hamsters, suggesting that favipiravir should be further evaluated as an antiviral treatment option for henipavirus infections. The overall goal of this application is to develop antiviral treatment options for infections caused by henipaviruses. Our hypothesis is that favipiravir will demonstrate therapeutic antiviral efficacy against all human pathogenic Nipah virus strains and Hendra virus in a disease-relevant and widely accepted small animal model, will be efficacious in a post-exposure setting, and interrupt transmission. To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Optimize the therapeutic efficacy of favipiravir against henipavirus infection in the Syrian hamster model; and (2) Evaluate if favipiravir can evoke extinction of Nipah virus through lethal mutagenesis. The proposed studies will provide fundamental information for the further development of favipiravir as a broad-spectrum antiviral, and ultimately lead to the development of countermeasures against henipavirus infections.",,2023,University Of Texas Med Br Galveston,240000,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21480,5F31AI152332-02,Characterizing the human antibody response to henipavirus infection,"Project Summary RNA viruses comprise some of the most deadly human pathogens described to date, with new agents constantly emerging as humans encroach on once untouched ecosystems. Two such viruses, Hendra (HeV) and Nipah (NiV), were first described in 1994 and 1998, respectively, and have causes sporadic outbreaks of disease in humans in Australia and Southeast Asia. Recently, though, Nipah virus has begun spreading geographically into new regions of India, causing disease with mortality rates reaching close to 100%. Because of the ability to cause such high morbidity and mortality, coupled with the fact that human-to-human transmission has been observed with Nipah virus, the WHO designated these agents as priority diseases in 2018, with urgent needs for accelerated research and development of vaccines and therapeutics. Despite this urgency, no treatments or vaccines have been licensed to date to combat these viruses, and major gaps in knowledge surrounding the human immune response to Hendra and Nipah exist. The overarching goal of this proposal is to elucidate the molecular and structural mechanisms of neutralization by human monoclonal antibodies targeting the attachment glycoproteins of Hendra and Nipah viruses. I have isolated a large panel of monoclonal antibodies from a human subject inoculated with the Hendra equine vaccine and have shown that these antibodies bind to the attachment glycoproteins or Hendra and/or Nipah viruses. A subset of antibodies potently neutralize both Hendra and Nipah virus isolates. My central hypothesis is that human antibodies targeting the henipavirus attachment glycoprotein neutralize by blocking receptor attachment and/or preventing fusion. In Aim 1, I will use a flow cytometric assay and pre- and post-attachment neutralization tests with chimeric Cedar virus bearing Hendra or Nipah virus glycoproteins to determine the molecular mechanisms by which antibodies neutralize virus. I will elaborate on these findings in Aim 2 by using a variety of structural and biochemical techniques to map the antigenic sites on the henipavirus attachment glycoprotein, with an emphasis on antigenic sites that elicit potently neutralizing, cross-reactive antibodies. My studies to date suggest the most potent antibodies able to bind both Hendra and Nipah virus attachment glycoproteins function by blocking viral attachment to the host receptor ephrin-B2, but that at least one other distinct antigenic site elicits neutralizing antibodies that use a distinct mechanism to neutralize virus. This proposal will provide insight into the human humoral response to henipavirus infection and will help to rationally guide the design of vaccines and antibody therapeutics.",,2021,Vanderbilt University,10059,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Hendra virus infection,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P21481,1R41AI157095-01,Furopyrimidines as novel inhibitors of henipaviruses,"The emergence and reemergence of pathogenic viruses represent continuous infectious disease threats to public health. Among these, the paramyxoviruses, which include many important human and animal pathogens, also include two excellent examples of emerged, zoonotic viral pathogens of importance: the henipaviruses; Hendra virus (HeV) and Nipah virus (NiV). HeV and NiV have a uniquely broad host tropism capable of infecting at least 18 animal species across 6 orders of mammals. HeV and NiV can also cause a systemic and often fatal respiratory and/or neurological disease in 11 mammalian species including humans. These henipaviruses remain significant biothreats to humans and economically important livestock in Australia and throughout South East Asia. In addition, there are no vaccines or antivirals approved for human use. Thus new treatment options are urgently needed. This application defines a plan to develop potent, small molecule inhibitors, which inhibit henipavirus replication. We have identified compounds that inhibit replication of these viruses, with IC50 values in the nanomolar range. In this application, we propose three specific aims: (1) To optimize the lead (and backup) scaffold and select developmental candidates; (2) Develop the SAR in the henipavirus infectious assay and further investigate the mechanism of action (MOA) of the replication inhibitors; and (3) Select henipavirus inhibitors with in vitro ADME properties suitable for whole animal testing in an infectious animal model.",,2022,"CHICAGO BIOSOLUTIONS, INC.",299595,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21482,1F31AI152422-01A1,Roles of Pteropine Bat and Human TRIMs in Regulating Henipavirus Infection,"Project Summary Bat species are the natural hosts of several emerging and re-emerging viruses including henipaviruses (HNVs). Although infection with these viruses causes high case fatality rates in humans, bats appear tolerant. Old World fruit bats in the family Pteropodidae are the natural reservoirs of HNVs, including Henda (HeV) and Nipah (NiV). HNV-pteropine bat ecological interactions are well-studied, but the mechanisms underlying the limited immunopathology in pteropine bats following HNV infection are unknown. During HNV infection in humans, the antiviral type I interferon (IFN-I) pathways are suppressed in part through the antagonism of tripartite motif proteins (TRIMs). TRIMs are involved in modulating antiviral immune responses including IFN-I production and signaling pathways. Some members of the TRIM E3 ubiquitin ligase family stimulate the IFN-I and pro-inflammatory antiviral pathways to promote viral clearance while others antagonize these pathways to limit immune-associated pathology. We have generated preliminary data that demonstrates NiV activates the IFN-I signaling pathway human cells late in infection, but IFN-I signaling remains antagonized efficiently in bat cells throughout the duration of infection. Based on this observation, we predict that bats have evolved to express a TRIM in response to NiV infection that negatively regulates the cytoplasmic RNA recognition pathway to prevent the cytopathic effects of innate immune signaling. Previously, we described the role of NiV matrix protein (NiV-M) in the degradation of human TRIM6, which inhibits TRIM6-mediated activation of IKKε- dependent IFN-I production and signaling. We found that bat TRIM6 interacts with NiV-M, but bat TRIM6 resists NiV-M mediated degradation. Due to this species-specific difference, we are interested in identifying the mechanisms that confer degradation resistance to bat TRIM6 and understanding the roles of TRIM6 during NiV infection. In this proposal, we hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human, cells that promotes tolerance, and that species-specific differences in NiV-M-mediated TRIM6 degradation influences the course of infection. We will interrogate our hypothesis through two specific aims: (1) to identify pteropine and human TRIM orthologs differentially expressed after NiV infection and determine their roles in innate immune regulation and (2) To elucidate the mechanistic roles of human and bat TRIM6 in regulating NiV infection. Overall, the results of the proposed study will promote our understanding of the molecular regulation of pteropine bat IFN-I pathways and potentially identify factors that facilitate bats’ tolerance to HNVs. Elucidating the mechanisms that promote tolerance to HNV may serve as a basis for the development of human therapeutics.",,2023,University Of Texas Med Br Galveston,34754,Animals | Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Vector biology,2021 +P21483,5F31AI154739-02,Elucidating the molecular determinants of Henipavirus envelope-antibody and envelope-receptor interactions on viral entry,"PROJECT SUMMARY: The identification of new Henipaviruses (HNVs) in Africa, China and Australia lend way to concerns about the risk of possible spillover events. Yet, there are no FDA approved therapeutics and the role of receptor usage on pathogenicity is still undetermined. Within this proposal, we aim to leverage our extensive preliminary results to further our understanding of the molecular determinants of envelope-antibody and envelope-receptor interactions on viral neutralization and viral pathogenicity. In recent work, we have identified an immune- accessible region on the NiV and HeV fusion glycoprotein that is targeted by several antibodies. Experiments proposed in Aim 1 will elucidate a mechanism for how these antibodies neutralize HNVs and will characterize novel antibodies against the divergent GhV fusion glycoprotein by utilizing a rapid, directed-evolution platform to identify escape mutants. Additionally, we have performed structure-guided mutagenesis to better understand HNV receptor binding protein and receptor interactions. The experiments directly proposed in Aim 2 will further characterize these mutants and assess the ability to confer use of this receptor to other HNVs using viruses. The work proposed here will ultimately support the development of HNV therapeutics and the understanding of the contributions of receptor usage on HNV pathogenicity.",,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,44436,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21484,1R13AI150022-01,3rd International Infectious Diseases of Bats Symposium,"Summary / Abstract In recent years, several bat-borne zoonotic diseases have emerged that cause substantial morbidity and mortality in humans. Many of these are caused by viruses that require the highest biosafety containment, including the ebolaviruses, Marburg virus, and Hendra and Nipah viruses. Other high containment pathogens that are bat-borne include SARS-CoV, MERS-CoV, and rabies virus, and two unusual bat-specific influenza viruses, H17N10 and H18N11 were recently discovered. To date, more than 200 viruses have been isolated from, or detected in, bats. Considering that about 1200 species of bats have been identified, they are likely underappreciated as sources of infectious diseases. Moreover, bats are also afflicted by infectious diseases, including rabies, Lloviu filovirus, Tacaribe virus and the fungus Geomyces destructans that causes white nose syndrome that has killed more than 5 million bats in North America. Despite the importance of bats as reservoirs of infectious agents, little is known about their biology or immunology, which presents a significant obstacle for understanding the ecology and spillover risks of infectious agents hosted by bats. The 3rd Bat- borne Infectious Diseases Symposium will provide an interactive forum for biomedical scientists, physicians, veterinarians and bat biologists to share research and to foster collaborations to study infectious diseases of bats. Several internationally-renowned scientists have agreed to present at the meeting, which should facilitate greater interest among the infectious disease community.",,2022,Colorado State University,8865,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Other,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Health Systems Research,Animal source and routes of transmission | Vector biology | Health information systems,2021 +P21485,5U01AI153420-02,Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks,"Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.",,2025,"ECOHEALTH ALLIANCE, INC.",574984,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21486,3U01AI151801-02S1,West African Center for Emerging Infectious Diseases,"Arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV) and Zika (ZIKV), as well as rodent- and bat-borne viruses such as Lassa fever and probably Ebola, are among the most important causes of emerging infectious diseases, and many circulate enzootically in W. Africa. The mechanisms whereby these and other zoonotic African viruses emerge and spread remain obscure, along with the understanding of their disease burden and varied clinical outcomes. The West African Center for Emerging Infectious Diseases will address these critical gaps through field studies of enzootic transmission, and clinical studies of human exposure and disease outcome. Our surveillance of humans, and wild animals, including bats (probable hosts of filoviruses, coronaviruses and henipaviruses), and mosquitoes/ticks, will likely identify new emerging viral pathogens. Further, the infrastructure and local expertise developed through these projects in Senegal, Sierra Leone and Nigeria, along with biosafety/biosecurity training and improved diagnostics, will also prepare the region for future outbreaks of emerging viral and other infectious diseases. The Center’s aims are to: 1. Study zoonotic arboviruses in Senegal, Sierra Leone and Nigeria, including identification and characterization of critical reservoir and amplification hosts, enzootic and epidemic vectors, temporal patterns of enzootic and epidemic circulation, levels of human exposure, immune responses and disease outcomes. The emphasis will be on the 4 “urban” (human amplified) arboviruses: CHIKV, DENV, YFV and ZIKV, but other known and possibly unknown viruses will also be studied. Risk maps will be generated. 2. In Sierra Leone and Nigeria, study the circulation among rodent hosts and infections of humans by Lassa virus, including identification of viral determinants of hemorrhagic disease severity and sequelae outcomes, and determination of the mechanisms of strain virulence variation. Risk maps will also be generated. 3. Perform surveillance in bats to identify potential sources of Ebola virus in W. Africa as well as other known or unknown zoonotic pathogens, including coronaviruses and henipaviruses that may be causing human disease, and which may explain the origins of emerging pathogens such as Nipah and MERS coronavirus. 4. Establish biocontainment and biosecurity training programs, advanced yet affordable viral genomics capabilities, and comprehensive diagnostics to support these aims as well as to improve research infrastructure and future outbreak responses in W. Africa. Our results will increase the mechanistic understanding of zoonotic viral maintenance and emergence, etiologies of febrile and hemorrhagic diseases, diverse disease outcomes, and risks for local and international spread. Novel viruses with emergence potential will likely be discovered, and existing collaborations between the Univ. of TX Medical Branch and its partners in Senegal, Sierra Leone, and Nigeria, as well as research infrastructure, will be strengthened to prepare for and respond quickly and effectively to future outbreaks.",,2025,University Of Texas Med Br Galveston,521027,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Arenaviridae | Coronavirus | Filoviridae | Flaviviridae | Paramyxovirdiae,,,,,,,,,Lassa fever | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Zika virus disease | Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Vector biology | Disease susceptibility",2020 +P21487,5U01AI151801-02,West African Center for Emerging Infectious Diseases,"Arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV) and Zika (ZIKV), as well as rodent- and bat-borne viruses such as Lassa fever and probably Ebola, are among the most important causes of emerging infectious diseases, and many circulate enzootically in W. Africa. The mechanisms whereby these and other zoonotic African viruses emerge and spread remain obscure, along with the understanding of their disease burden and varied clinical outcomes. The West African Center for Emerging Infectious Diseases will address these critical gaps through field studies of enzootic transmission, and clinical studies of human exposure and disease outcome. Our surveillance of humans, and wild animals, including bats (probable hosts of filoviruses, coronaviruses and henipaviruses), and mosquitoes/ticks, will likely identify new emerging viral pathogens. Further, the infrastructure and local expertise developed through these projects in Senegal, Sierra Leone and Nigeria, along with biosafety/biosecurity training and improved diagnostics, will also prepare the region for future outbreaks of emerging viral and other infectious diseases. The Center’s aims are to: 1. Study zoonotic arboviruses in Senegal, Sierra Leone and Nigeria, including identification and characterization of critical reservoir and amplification hosts, enzootic and epidemic vectors, temporal patterns of enzootic and epidemic circulation, levels of human exposure, immune responses and disease outcomes. The emphasis will be on the 4 “urban” (human amplified) arboviruses: CHIKV, DENV, YFV and ZIKV, but other known and possibly unknown viruses will also be studied. Risk maps will be generated. 2. In Sierra Leone and Nigeria, study the circulation among rodent hosts and infections of humans by Lassa virus, including identification of viral determinants of hemorrhagic disease severity and sequelae outcomes, and determination of the mechanisms of strain virulence variation. Risk maps will also be generated. 3. Perform surveillance in bats to identify potential sources of Ebola virus in W. Africa as well as other known or unknown zoonotic pathogens, including coronaviruses and henipaviruses that may be causing human disease, and which may explain the origins of emerging pathogens such as Nipah and MERS coronavirus. 4. Establish biocontainment and biosecurity training programs, advanced yet affordable viral genomics capabilities, and comprehensive diagnostics to support these aims as well as to improve research infrastructure and future outbreak responses in W. Africa. Our results will increase the mechanistic understanding of zoonotic viral maintenance and emergence, etiologies of febrile and hemorrhagic diseases, diverse disease outcomes, and risks for local and international spread. Novel viruses with emergence potential will likely be discovered, and existing collaborations between the Univ. of TX Medical Branch and its partners in Senegal, Sierra Leone, and Nigeria, as well as research infrastructure, will be strengthened to prepare for and respond quickly and effectively to future outbreaks.",,2025,University Of Texas Med Br Galveston,1545268,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Arenaviridae | Coronavirus | Filoviridae | Flaviviridae | Paramyxovirdiae | Unspecified,,,,,,,,,Lassa fever | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Zika virus disease | Nipah and henipaviral disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Vector biology | Disease susceptibility",2020 +P21488,1R01AI160226-01,Preclinical development of a vaccine for Nipah virus,"PROJECT SUMMARY/ABSTRACT Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is also categorized as a Category C priority pathogen by several US Government agencies because of the concern for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018 List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ÃŽÂ""G) vesicular stomatitis virus (rVSVÃŽÂ""G) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses. In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when used as single injection vaccines. This new data is critically important in the context of containing outbreaks as the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that works rapidly with a single administration. Development of a replication restricted platform that provides improved safety without compromising efficacy is a highly significant advancement and can be applied to other viruses with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV (rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank (RVB), a manufacturing process, and conduct of GLP-safety toxicology.",,2026,University Of Texas Med Br Galveston,1415990,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21489,1F31AI152332-01,Characterizing the human antibody response to henipavirus infection,"Project Summary RNA viruses comprise some of the most deadly human pathogens described to date, with new agents constantly emerging as humans encroach on once untouched ecosystems. Two such viruses, Hendra (HeV) and Nipah (NiV), were first described in 1994 and 1998, respectively, and have causes sporadic outbreaks of disease in humans in Australia and Southeast Asia. Recently, though, Nipah virus has begun spreading geographically into new regions of India, causing disease with mortality rates reaching close to 100%. Because of the ability to cause such high morbidity and mortality, coupled with the fact that human-to-human transmission has been observed with Nipah virus, the WHO designated these agents as priority diseases in 2018, with urgent needs for accelerated research and development of vaccines and therapeutics. Despite this urgency, no treatments or vaccines have been licensed to date to combat these viruses, and major gaps in knowledge surrounding the human immune response to Hendra and Nipah exist. The overarching goal of this proposal is to elucidate the molecular and structural mechanisms of neutralization by human monoclonal antibodies targeting the attachment glycoproteins of Hendra and Nipah viruses. I have isolated a large panel of monoclonal antibodies from a human subject inoculated with the Hendra equine vaccine and have shown that these antibodies bind to the attachment glycoproteins or Hendra and/or Nipah viruses. A subset of antibodies potently neutralize both Hendra and Nipah virus isolates. My central hypothesis is that human antibodies targeting the henipavirus attachment glycoprotein neutralize by blocking receptor attachment and/or preventing fusion. In Aim 1, I will use a flow cytometric assay and pre- and post-attachment neutralization tests with chimeric Cedar virus bearing Hendra or Nipah virus glycoproteins to determine the molecular mechanisms by which antibodies neutralize virus. I will elaborate on these findings in Aim 2 by using a variety of structural and biochemical techniques to map the antigenic sites on the henipavirus attachment glycoprotein, with an emphasis on antigenic sites that elicit potently neutralizing, cross-reactive antibodies. My studies to date suggest the most potent antibodies able to bind both Hendra and Nipah virus attachment glycoproteins function by blocking viral attachment to the host receptor ephrin-B2, but that at least one other distinct antigenic site elicits neutralizing antibodies that use a distinct mechanism to neutralize virus. This proposal will provide insight into the human humoral response to henipavirus infection and will help to rationally guide the design of vaccines and antibody therapeutics.",,2023,Vanderbilt University,30231,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P21491,1F31AI154739-01,Elucidating the molecular determinants of Henipavirus envelope-antibody and envelope-receptor interactions on viral entry,"PROJECT SUMMARY: The identification of new Henipaviruses (HNVs) in Africa, China and Australia lend way to concerns about the risk of possible spillover events. Yet, there are no FDA approved therapeutics and the role of receptor usage on pathogenicity is still undetermined. Within this proposal, we aim to leverage our extensive preliminary results to further our understanding of the molecular determinants of envelope-antibody and envelope-receptor interactions on viral neutralization and viral pathogenicity. In recent work, we have identified an immune- accessible region on the NiV and HeV fusion glycoprotein that is targeted by several antibodies. Experiments proposed in Aim 1 will elucidate a mechanism for how these antibodies neutralize HNVs and will characterize novel antibodies against the divergent GhV fusion glycoprotein by utilizing a rapid, directed-evolution platform to identify escape mutants. Additionally, we have performed structure-guided mutagenesis to better understand HNV receptor binding protein and receptor interactions. The experiments directly proposed in Aim 2 will further characterize these mutants and assess the ability to confer use of this receptor to other HNVs using viruses. The work proposed here will ultimately support the development of HNV therapeutics and the understanding of the contributions of receptor usage on HNV pathogenicity.",,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,45360,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21492,1U01AI153420-01,Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks,"Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.",,2025,"ECOHEALTH ALLIANCE, INC.",580858,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Paramyxovirdiae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21493,1U01AI151801-01,West African Center for Emerging Infectious Diseases,"Arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV) and Zika (ZIKV), as well as rodent- and bat-borne viruses such as Lassa fever and probably Ebola, are among the most important causes of emerging infectious diseases, and many circulate enzootically in W. Africa. The mechanisms whereby these and other zoonotic African viruses emerge and spread remain obscure, along with the understanding of their disease burden and varied clinical outcomes. The West African Center for Emerging Infectious Diseases will address these critical gaps through field studies of enzootic transmission, and clinical studies of human exposure and disease outcome. Our surveillance of humans, and wild animals, including bats (probable hosts of filoviruses, coronaviruses and henipaviruses), and mosquitoes/ticks, will likely identify new emerging viral pathogens. Further, the infrastructure and local expertise developed through these projects in Senegal, Sierra Leone and Nigeria, along with biosafety/biosecurity training and improved diagnostics, will also prepare the region for future outbreaks of emerging viral and other infectious diseases. The Center’s aims are to: 1. Study zoonotic arboviruses in Senegal, Sierra Leone and Nigeria, including identification and characterization of critical reservoir and amplification hosts, enzootic and epidemic vectors, temporal patterns of enzootic and epidemic circulation, levels of human exposure, immune responses and disease outcomes. The emphasis will be on the 4 “urban” (human amplified) arboviruses: CHIKV, DENV, YFV and ZIKV, but other known and possibly unknown viruses will also be studied. Risk maps will be generated. 2. In Sierra Leone and Nigeria, study the circulation among rodent hosts and infections of humans by Lassa virus, including identification of viral determinants of hemorrhagic disease severity and sequelae outcomes, and determination of the mechanisms of strain virulence variation. Risk maps will also be generated. 3. Perform surveillance in bats to identify potential sources of Ebola virus in W. Africa as well as other known or unknown zoonotic pathogens, including coronaviruses and henipaviruses that may be causing human disease, and which may explain the origins of emerging pathogens such as Nipah and MERS coronavirus. 4. Establish biocontainment and biosecurity training programs, advanced yet affordable viral genomics capabilities, and comprehensive diagnostics to support these aims as well as to improve research infrastructure and future outbreak responses in W. Africa. Our results will increase the mechanistic understanding of zoonotic viral maintenance and emergence, etiologies of febrile and hemorrhagic diseases, diverse disease outcomes, and risks for local and international spread. Novel viruses with emergence potential will likely be discovered, and existing collaborations between the Univ. of TX Medical Branch and its partners in Senegal, Sierra Leone, and Nigeria, as well as research infrastructure, will be strengthened to prepare for and respond quickly and effectively to future outbreaks.",,2025,UNIVERSITY OF TEXAS MED BR GALVESTON,1702711,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Arenaviridae | Filoviridae | Flaviviridae | Paramyxovirdiae,,,,,,,,,Lassa fever | Ebola virus disease | Zika virus disease | Nipah and henipaviral disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Vector biology",2020 +P21501,1R44AI177045-01,Prophylactic Immunotherapy for Marburg Virus Disease Outbreak Control,"The ebolaviruses (EBOV, SUDV, BDBV) and marburgviruses (MARV and RAVV), cause periodic outbreaks of severe viral hemorrhagic fever with very high mortality rates. The 2013-2016 Ebola virus disease (EVD) outbreak in West Africa highlighted the serious nature of a filovirus epidemic and its regional and global implications. This outbreak took an enormous toll on people at the front line of the epidemic control, i.e., physicians, nurses, hospital personnel, social workers, and other support staff. Many nurses and physicians lost their lives helping patients and many left their profession out of fear of exposure. The near breakdown of the local healthcare system further fueled the spread of the virus across the region. Therefore, protection of the first responders must be a high priority and is critical for successful outbreak control. Currently, while a prophylactic vaccine is available for EVD, there are no therapeutic or prophylactic countermeasures available for Marburg virus disease (MVD) which has led to many outbreaks and as recently as June 2022. The objective of this proposal is to develop an effective immunoprophylactic for protection of first responders against MVD. Such a product mut be 1) extremely potent to enable economically affordable low dose levels, and 2) have extended bioavailability to provide a reasonably long duration of protection. We and others have isolated several classes of neutralizing monoclonal antibodies (mAbs) for ebolaviruses. However, for marburgviruses only a single class of mAbs against the glycoprotein (GP) has been described that all target a single epitope within the receptor binding site (RBS) of MARV and RAVV GP. Now, using a novel immunization and B cell selection approach with rationally designed antigens we have succeeded in identifying a new class of mAbs that bind to a novel epitope and neutralize marburgviruses at sub- to low-nM concentrations and are up to 100-fold more potent than the RBS binders. A lead antibody, R217, has been selected and shown to protect against MVD in mice, guinea pigs, and nonhuman primates (NHPs). In this SBIR project we propose to engineer the Fc portion of this macaque-human chimeric antibody by introducing mutations (YTE) in the FcRn binding region to extend the half-life of the antibody and evaluate the efficacy of the product. In Aim 1 R217-YTE will be produced in ExpiCHO cells and fully characterized. Pharmacokinetics (PK) will be evaluated in NHPs. In Aim 2, the efficacy of R217-YTE against MVD will be evaluated in the settings of pre- and post-exposure prophylaxis and the required dose level and serum neutralization activity required for protection will be determined. Aim 3 will be focused on generation of a stable manufacturing cell line in CHO cells and a research cell bank to be used for production of future GMP cell banks. If successful, we anticipate further development of the product under DoD or BARDA funding and approval under FDA Animal Rule.",,2026,"ABVACC, INC.",986248,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2023 +P21502,1R44AI179371-01,Monoclonal Antibody Cocktail for Treatment of Marburg Virus Disease,"Project Summary Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and nonhuman primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola Virus Disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. This outbreak spurred an unprecedented global effort for development of vaccines and therapeutics for EVD and led to an approved vaccine and two monoclonal antibody (mAb) therapeutics. Importantly studies with EBOV mAbs and later SARS-CoV2 mAbs established the value of mAb cocktails for effective treatment of viral diseases. In contrast to EVD, development of therapeutics for Marburg Virus Disease (MVD) has been lagging despite several MVD outbreaks including one in 2022. The investigators on this MPI Phase I/II Fast Track SBIR application have developed two classes of mAbs targeting non-overlapping epitopes within the receptor binding site (RBS) and the internal fusion loop (IFL) of MARV glycoprotein (GP). The RBS-binding mAb (MR186), provides protection primarily through effector functions, while the IFL-binder (R217) is the most potent neutralizing MARV mAb discovered to-date. MR186 has been engineered to enhance bioavailability using YTE mutation in the Fc portion, and produced in a fucosyl- transferase deficient CHO cell line to enhance effector functions (MR186-YTEAF). We are currently introducing YTE mutations into R217 Fc to generate the therapeutic candidate R217-YTE. In this proposed project we harness these complementary mechanisms of action to develop a highly effective cocktail of these two mAbs for MVD treatment. Use of mAb cocktail is also expected to reduce the risk of escape variant. The proposal has four Specific Aims. In Aim 1 (Phase I portion), R217-YTE will be produced in ExpiCHO cells and fully characterized. Superior efficacy of the cocktail will be demonstrated in a guinea pig model of MARV-Angola and this milestone will serve for transition to Phase II SBIR. Phase II Portion starts with Aim 2, in which the efficacy of the cocktail will be tested in NHP models in series of adaptively designed NHP experiments and finally the superior efficacy will be formally demonstrated in comparison with the individual mAbs. In Aim 3 we will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the antibodies in sera from a number of NHP efficacy studies including studies performed in Aim 1. Correlations between PK/PD data and clinical outcome will be explored. Aim 4 we will be focused on generation of stable manufacturing cell lines in CHO cells and at lease four clones of each mAb will be produced to be used for future GMP cell banks. If successful, we anticipate further development of the product under DoD or BARDA funding and approval under FDA Animal Rule.",,2024,"ABVACC, INC.",293392,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21520,1R01AI179744-01,The role of mTOR dysregulation in poxvirus infection,"PROJECT SUMMARY/ABSTRACT Although smallpox was formally declared to have been eradicated in 1980, molluscum contagiosum is widespread and a variety of zoonotic poxviruses continually infect and adapt to humans. This is exemplified by monkeypox/Mpox virus, which causes outbreaks in humans with increasing frequency and resulted in a global outbreak and declaration of a new WHO poxvirus emergency in 2022. Yet several other poxviridae family members are used as vaccine vectors and oncolytics. Beyond their direct medical significance, studies of poxviruses have a long history of providing new insights into fundamental aspects of cell biology and immunology, due in part to their unusual replication cycle and complex immune evasion strategies. Other than the singular, related African Swine Fever Virus, poxviruses are the only mammalian DNA viruses that replicate entirely in the cytoplasm. To do this, poxviruses encode their own fully functional DNA replication, transcription and mRNA biogenesis machinery, forming large cytoplasmic replication sites called “viral factories”. Despite this, poxviruses remain dependent upon their host cell’s mRNA translation machinery and metabolic pathways to complete their replication cycle, while their mode of replication makes them highly vulnerable to cytosolic sensors aimed at detecting their presence and mounting antiviral responses. These metabolic and sensing processes are intertwined yet how poxviruses control them is both complex and poorly understood. Through co-immunoprecipitation and mass spectrometry-based screening in biologically relevant primary cells, we discovered that a highly conserved poxvirus protein, called F17, targets the central metabolic sensor and effector kinase, mammalian/mechanistic Target of Rapamycyin (mTOR) in unique ways. Unlike other viruses that target upstream signaling to mTOR to indirectly stimulate or repress its activity, we find that F17 directly targets the two distinct mTOR Complexes 1 and 2 (mTORC1, mTORC2) to “dysregulate” their activity. This is achieved through F17 binding to unique N-terminal conserved domains in the mTOR regulatory subunits, Raptor and Rictor, resulting in their competitive sequestration from binding to mTOR. Moreover, we find that F17 is required to block Interferon Stimulated Gene (ISG) responses that are initiated by the cytosolic sensor, cGAS. While the precise nature of these host responses and how F17 counteracts them remains unclear, additional preliminary data suggests that while other viral proteins function to counteract cGAS-mediated responses to viral DNA, F17 instead blocks cGAS-mediated responses that are driven by mitochondrial DNA release, and which require mTOR-mediated metabolic rewiring to drive ISG production. This proposal will determine the structural basis of mTOR dysregulation by F17, how this contributes to virus replication and spread in various biologically relevant human cell types, and how F17 counteracts mitochondrial-driven antiviral responses. Upon completion, this proposal will illuminate previously unrecognized aspects of innate responses and viral countermeasures that occur during poxvirus infection.",,2028,Northwestern University At Chicago,611807,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P21521,5R01AI168023-02,Understanding the Function of F13 as a Matrix Protein for Poxvirus Intracellular Envelopment,"Poxviruses are a large family of DNA viruses with several members capable of infecting and causing disease in humans. Whereas the most notorious member, variola virus, is the causative agent of smallpox and was eradicated from natural infection, there are still concerns about a clandestine release during a biological attack. In addition, other members of the family, such as monkeypox virus, have raised concern about epizootic infections that are capable of causing epidemics. For these reasons several poxviruses are listed as Category A priority pathogens by NIH/NIAID. Poxviruses produce two infectious forms, intracellular mature virus (IMV) and extracellular virus (EV). EV are formed by the intracellular envelopment of IMV and are critical for cell-to-cell spread, systemic infection, and pathogenesis. The long-term goal of our research is to understand the molecular mechanisms employed by orthopoxviruses to envelope, transport, and release infectious EV. Only 9 viral proteins are known to be unique to the EV form. Whereas some functions have be assigned to these 9 proteins, none of them have been shown to be a matrix- like protein and make a direct connection with the IMV form of the virus to coordinate envelopment. The immediate goal of this application is to better define the role of the putative matrix protein F13 in intracellular envelopment of EV and its relationship with the other EV glycoproteins. We propose 3 aims to better understand the function of F13: 1) Interrogate interactions between F13 and IMV surface proteins. We hypothesize that F13 acts as a matrix protein and provides a link between the outer EV membrane and the inner IMV particle and facilitates interactions with IMV at the site of intracellular envelopment, the TGN. In this aim we will further characterize interactions between F13 and IMV surface proteins. 2) Uncover cellular and viral proteins that interact with the putative matrix protein F13. We will use BioID to identify viral and cellular proteins that interact with F13 during specific stages of envelopment. 3). Determine the relationship between F13, glycoprotein content, EV cell binding, and non fusogenic dissolution for virus entry. We will utilize a panel of recombinant viruses to determine how F13 controls glycoprotein content and how this effects cell binding and entry of EV. The results obtained from these studies will provide greater insight into the molecular mechanism poxviruses use to produce infectious EV, spread cell-to-cell, and cause disease in their hosts. This information will in turn inform intelligent decisions in designing recombinant poxvirus vectors for both vaccines and oncolytic platforms.",,2027,University Of Rochester,346500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21522,9R01AI178795-09A1,Gigapixel Next-Generation-Sequencing: An Ultra-Sensitive Diagnostic for Infections of the CNS,"Infectious diseases remain a significant cause of morbidity worldwide, highlighting the critical need for accurate diagnosis. However, shared symptoms among different infections and the emergence of drug resistance make diagnosis and treatment selection challenging. In this competing renewal, we propose to develop Gigapixel NGS (gNGS) to enable rapid, sensitive, and information-rich infectious disease diagnosis. gNGS builds upon our Gigapixel PCR (gPCR) technology by incorporating powerful next-generation sequencing capabilities. By utilizing double emulsion vesicles for single cell assays, gNGS eliminates the need for specialized droplet analyzers and allows common flow cytometers to be used for genome isolation. Our goal in this renewal is to leverage the capabilities of Gigapixel NGS to detect, isolate, and sequence infectious pathogen genomes from patient samples, which will improve the efficiency and sensitivity of pathogen sequencing. We will collaborate with Dr. Charles Chiu, a renowned expert in infectious disease diagnostics who leads the CLIA-certified pathogen lab at UCSF, to develop clinical workflows and bioinformatic tools for interrogating the recovered genomes for relevant biomarker sequences, including virulence factors and drug resistance genes. Dr. Chiu's expertise in infectious disease diagnostics and practical experience in clinical sample sequencing for pathogen detection will ensure that the new diagnostic is effective and practical in a clinical setting.",,2028,"University Of California, San Francisco",549398,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Viral evolution in different contexts & implications,United States of America,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2023 +P21523,75N92022D00014-0-759202300005-1,RADX Independent Test Assessment Program for MPOX Lesion Panel - Coordination Center,"The National Institutes of Health (NIH) Rapid Acceleration of Diagnostics (RADxÃ'®) Tech program has established the Independent Test Assessment Program (ITAP) in order to accelerate regulatory review and availability of high-quality, accurate, and reliable diagnostic tests.",,2024,MASSACHUSETTS GENERAL HOSPITAL,153450,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics","Development of equitable, accessible, safe & effective diagnostics (including POC)",United States of America,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research",Diagnostics | Health leadership and governance,2023 +P21524,75N92022D00015-0-759202300002-1,RADX Independent Test Assessment Program for MPOX Lesion Panel - Validation Center,"The National Institutes of Health (NIH) Rapid Acceleration of Diagnostics (RADxÃ'®) Tech program has established the Independent Test Assessment Program (ITAP) in order to accelerate regulatory review and availability of high-quality, accurate, and reliable diagnostic tests.",,2024,Emory University,186787,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics","Development of equitable, accessible, safe & effective diagnostics (including POC)",United States of America,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research",Diagnostics | Health leadership and governance,2023 +P21525,75N92022D00013-0-759202300003-1,RADX Independent Test Assessment Program for MPOX Lesion Panel - Commercialization Center,"The National Institutes of Health (NIH) Rapid Acceleration of Diagnostics (RADxÃ'®) Tech program has established the Independent Test Assessment Program (ITAP) in order to accelerate regulatory review and availability of high-quality, accurate, and reliable diagnostic tests.",,2024,VENTUREWELL,659763,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics","Development of equitable, accessible, safe & effective diagnostics (including POC)",United States of America,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research",Diagnostics | Health leadership and governance,2023 +P21526,75N91019D00024-P00001-759102200024-2,Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Mpox Vaccine,"This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen in healthy, vaccinia-naïve adults 18 to 50 years of age.",,2024,"LEIDOS BIOMEDICAL RESEARCH, INC.",6645185,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines | Immunisation strategies to optimise use of available vaccines",United States of America,,"Vaccines research, development and implementation",Phase 2 clinical trial,2022 +P21527,1UC7AI180308-01,Research Resources and Workforce Development for the Rocky Mountain Regional Biocontainment Laboratory at Colorado State University,"Project Summary: The Rocky Mountain Regional Biocontainment Laboratory (RMRBL) at Colorado State University (CSU) has been responsive to the national RBL mission to: 1) “Conduct research on biodefense and emerging infectious disease agents”; 2) “Be available and prepared to assist national, state, and local public health efforts in the event of a bioterrorism or infectious disease emergency” since its opening and full commissioning in 2008. Researchers at the RMRBL and their collaborators rapidly pivoted in response to the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), working on host-derived therapeutics, vaccines, and identifying other potential zoonotic reservoirs as spillover opportunities in wildlife and domestic animals. Our researchers similarly pivoted this past year to work on countermeasures in response to the re-emergence of Mpox, while also continuing to address high consequence pathogens that have chronically plagued public health systems, such as Mycobacterium tuberculosis, the causative agent of Tuberculosis. Beyond our demonstrated ability to rapidly address research and research service needs on pathogens with pandemic potential, our team contributes to training, outreach, and access of our facility via sponsored fellowships, visiting scholars’ programs, workshops, conferences, and through collaborations. Despite these gains, our RMRBL BSL3 suites are aged, requiring constant investments to maintain safe, secure and compliant BSL3 facilities. RMRBL BSL3 researchers, support staff, and biosafety professionals are vulnerable to the strain of the work environment, limited resources, funding gaps, and opportunities to engage in less risky fields equipped with cutting edge technologies. In this application, we respond to the challenges facing the RMRBL BSL3 laboratories with 3 Cores. Core 1 includes an improved management structure, systematic replacement of deprecating scientific instruments, and comprehensive and proactive maintenance of existing facilities needs to ensure compliance and continuous functioning. Operation of the RMRBL BSL3 is additionally enhanced to improve the working environment and increase consistency for operations research support and animal husbandry staff. Core 2’s initiatives seek to develop training programs responsive to adult learning and education best practices, ensuring improved safety and safety compliance in persons working in the BSL3. Biosecurity upgrades will improve the safety and security climate in anticipation of new national standards, and integration between research teams and the office of Biosafety in constructing and training in technical standard operating procedures will accelerate safe performance and technical competence. Finally, Core 3 synthesizes our research strengths to develop a uniquely qualified Biocontainment Research Resources Core, bringing together opportunities to exploit team talent and perform innovative research. Combined, our three Cores ensure that the RMRBL BSL3 facilities are always ‘warm ready’ â€Â"" to face and combat the next pathogenic pandemic threat.",,2028,COLORADO STATE UNIVERSITY,2751527,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Poxviridae | Novel Pathogen,,,,,,,,,Severe Acute Respiratory Syndrome (SARS) | Mpox | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2023 +P21528,75N91019D00024-P00012-759102000004-1,Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Mpox Vaccine,"This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen in healthy, vaccinia-naïve adults 18 to 50 years of age.",,2024,"LEIDOS BIOMEDICAL RESEARCH, INC.",429747,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines | Immunisation strategies to optimise use of available vaccines",United States of America,,"Vaccines research, development and implementation",Phase 2 clinical trial,2020 +P21529,75N93021C00012-P00008-9999-6,Statistical Data Coordinating Center: Monkeypox Clinical Research Support,"The goal of the Statistical and Data Coordinating Center is to provide comprehensive statistical support, data management and analysis activities for DMID-sponsored clinical research trials. This includes internet-based electronic data collection, data management, data quality control and a specimen tracking system. In addition, the contractor provides consultation on statistics, study design, appropriate control groups, sample size, power calculations, randomization, stratification, and analysis.",,2023,"THE EMMES COMPANY, LLC",1300000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2021 +P21530,1R01AI168023-01A1,Understanding the Function of F13 as a Matrix Protein for Poxvirus Intracellular Envelopment,"Poxviruses are a large family of DNA viruses with several members capable of infecting and causing disease in humans. Whereas the most notorious member, variola virus, is the causative agent of smallpox and was eradicated from natural infection, there are still concerns about a clandestine release during a biological attack. In addition, other members of the family, such as monkeypox virus, have raised concern about epizootic infections that are capable of causing epidemics. For these reasons several poxviruses are listed as Category A priority pathogens by NIH/NIAID. Poxviruses produce two infectious forms, intracellular mature virus (IMV) and extracellular virus (EV). EV are formed by the intracellular envelopment of IMV and are critical for cell-to-cell spread, systemic infection, and pathogenesis. The long-term goal of our research is to understand the molecular mechanisms employed by orthopoxviruses to envelope, transport, and release infectious EV. Only 9 viral proteins are known to be unique to the EV form. Whereas some functions have be assigned to these 9 proteins, none of them have been shown to be a matrix- like protein and make a direct connection with the IMV form of the virus to coordinate envelopment. The immediate goal of this application is to better define the role of the putative matrix protein F13 in intracellular envelopment of EV and its relationship with the other EV glycoproteins. We propose 3 aims to better understand the function of F13: 1) Interrogate interactions between F13 and IMV surface proteins. We hypothesize that F13 acts as a matrix protein and provides a link between the outer EV membrane and the inner IMV particle and facilitates interactions with IMV at the site of intracellular envelopment, the TGN. In this aim we will further characterize interactions between F13 and IMV surface proteins. 2) Uncover cellular and viral proteins that interact with the putative matrix protein F13. We will use BioID to identify viral and cellular proteins that interact with F13 during specific stages of envelopment. 3). Determine the relationship between F13, glycoprotein content, EV cell binding, and non fusogenic dissolution for virus entry. We will utilize a panel of recombinant viruses to determine how F13 controls glycoprotein content and how this effects cell binding and entry of EV. The results obtained from these studies will provide greater insight into the molecular mechanism poxviruses use to produce infectious EV, spread cell-to-cell, and cause disease in their hosts. This information will in turn inform intelligent decisions in designing recombinant poxvirus vectors for both vaccines and oncolytic platforms.",,2027,University Of Rochester,385000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21531,5R01AI151559-04,Advancement of poxvirus inhibitor,"Abstract Poxviruses are a large group of human pathogens that include the causative agent of smallpox, Monkeypox, and Cowpox. As poxvirus immunity around the world wanes there has been a concomitant increase in poxviral disease, leading to a growing need for small molecule therapeutics that protect against poxviral disease. There are several investigational drugs that have been used to treat cases of orthopoxvirus infection and one has been recently approved by the FDA for limited use, but viral resistance to this compound has been noted. The WHO, CDC and other agencies have stated a strong desire for at least two small molecule therapeutics that broadly target poxviruses due to the high perceived risk of poxviral disease both from endemic exposure as well as the potential purposeful release of smallpox as a bioterror agent. This goal has not yet been met. We have identified a family of non-nucleoside small molecules (“PDPMs”) that show broad spectrum antipoxviral activity and low/no toxicity to cells and suppress viral mRNA production. Our current data suggests is that the drug is targeting the poxvirus RNA polymerase (RNAP), which would be an ideal target that is highly conserved across all poxviruses. Through this proposal we will probe the potential of PDPMs to become effective antivirals, using medicinal chemistry approaches to identify compounds with high potency and favorable pharmacokinetic profiles. To aid and complement the therapeutic development of these molecules, we will use genetic, biochemical and chemical approaches to determine the target of the compound and the mechanism by which it blocks viral replication. Following the identification of high potency, pharmacologically favorable compounds, we will test their efficacy in animal models of poxvirus disease. These experiments will be carried out through an ongoing collaboration at the CDC. The CDC will oversee testing of PDPMs against smallpox and in efficacy determination in animal models of poxviral disease. When these efforts are completed they will enable advanced (towards first-in-human) testing of a new class of poxvirus inhibitor â€Â"" an inhibitor that has a mechanism of action complementary to the existing FDA approved compound and a broad protection profile, fulfilling the need for multi-compound protection from these significant human pathogens.",,2025,Boston University Medical Campus,656410,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21533,1UC7AI180307-01,"Resources, Workforce Development, and Animal Models for the Rutgers RBL","Overall ABSTRACT The Rutgers University Regional Biocontainment Laboratory (RBL) serves as a central facility to perform biosafety level three (BSL3) therapeutic, pathogenesis, and diagnostic research on high threat biological agents with a focus on Mycobacterium tuberculosis and SARS-CoV-2, as well as other category A, B, and C pathogens. The RBL serves academic and commercial entities within Rutgers University, the Northeast United States and nationally, while also engaging globally with companies and academic institutions through collaborations and research contracts. This proposal will provide support that enhances the RBL’s ability to fulfill its research and biothreat response/pandemic preparedness missions while also supporting an expanding faculty/staff. We propose to accomplish these goals by improving the RBL facilities, support services, BSL3 practice development and implementation and special services offerings though the execution of three aims: Aim 1. Establish a Facility management, maintenance and operations (FMMO) core. Aim 2. Establish a BSL-3 Practices core (Practice core). Aim 3. Establish a biocontainment research support service core devoted to developing animal models of BSL3 pathogens and associated support services (Animal models and related services, or AMRS core). The FMMO core will provide BSL3 and ABSL3 services, management and oversight, for routine animal husbandry, microbiology and virology services in support of investigators grant funded research projects while ensuring efficient operations and maintenance of the BSL3 facilities and providing trained staff to support the BSL3 building systems and equipment. The Practice core will develop and maintain standard operating procedures and training for research in the RBL BSL3 laboratories including best practices, emergency response, waste management, shipping, husbandry, select agent-specific practices and inventory. It will also develop and conduct biosecurity and disaster drills and liaise with other BSL3 laboratories within the RBL network as well as local, state and federal health agencies to coordinate operations and plan for joint responses to new infectious disease threats. The AMRS core will develop critical animal models including those of SARS-CoV2 and highly pathogenic influenza virus transmission, COVID-19 PASC, pulmonary impairment after TB (PIAT), and drug treatment models, and then support grant funded investigators in the performance of these models along with the advanced instrumentation needed to analyze these infected models and their tissues/cells in a BSL3 environment. Together, these three cores will significantly enhance the near- and long-term abilities of the RBL to address critical biothreats and emerging infectious diseases requiring study in a BSL3 laboratory setting, while also increasing our capacity to respond to the next public health emergency or pandemic.",,2028,RUTGERS BIOMEDICAL AND HEALTH SCIENCES,3970689,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2023 +P21535,1R01AI174892-01A1,The impacts of HIV-related service interruptions during COVID-19 pandemic in South Carolina,"Abstract The global COVID-19 pandemic has imposed unprecedented pressure on health systems and has interrupted public health efforts for other major health conditions, including HIV. HIV service interruptions in the forms of redeployment of staff, reallocation of resources, lack of equipment and medicine (e.g., shortages of HIV/STI testing kits, strained drug supply chain), and reduced access to care (e.g., travel restrictions, lock downs) may have a profound and long-term impact on HIV treatment cascade outcomes, especially given the evolving nature of the pandemic. There are several gaps in the existing literature in addressing HIV service interruptions and their consequences. These gaps include a lack of using large-scale, real-world, multi-type data with theoretical guidance; the focus on single or limited HIV treatment cascade outcomes; and limited efforts to identify factors that can mitigate the negative impacts of such interruptions to inform potential interventions and capacity building at state or local levels. In response to NOT-AI-21-057, we propose to comprehensively investigate HIV service interruptions during the COVID-19 pandemic following a socioecological model, assess their impacts on various outcomes of the HIV prevention and treatment cascade, and identify resilience resources for buffering impacts of interruptions on HIV treatment cascade outcomes. Specifically, we will assess HIV service interruptions in South Carolina (SC) since 2020 using operational report data of Ryan White HIV clinics, in-depth interview data with clinic leaders and providers, and HIV service utilization data based on both electronic health records (EHR) and publicly available cellphone-based HIV clinics visitation data. We will further explore how HIV service interruptions affects HIV prevention and treatment cascade outcomes at appropriate geospatial units based on the integration of multi-type datasets (e.g., EHR, geospatial data) from multiple sources. Finally, we will identify institutional-, community-, and structural-level factors (e.g., resilience resources) that may mitigate the adverse impacts of HIV service interruptions based on the triangulation of quantitative (EHR data, online survey data) and qualitative (in- depth interviews, focus group discussion) data regarding health infrastructure, social capital, and organizational preparedness. Our proposed research can lead to a better understanding of complicated HIV service interruptions in SC and resilience factors that can mitigate the negative effects of such interruptions on various HIV treatment cascade outcomes. The multi-level resilience resources identified through data triangulation will assist SC health departments and communities in developing strategic plans in response to this evolving pandemic and other future public health emergencies (e.g., monkeypox, disasters caused by climate change). The research findings can also inform public health policymaking and the practices of other Deep South states with similar sociocultural contexts and experiences of HIV service interruptions during the pandemic.",,2028,University Of South Carolina At Columbia,699042,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P21536,1R01AI177859-01,Expanding Swabseq sequencing technology to enable readiness for emerging pathogens,"This application aims to develop improved methods for detecting novel pathogens that can be deployed on a large scale and are flexible to multiple pathogens. The method uses the power of next generation sequencing technology to analyse hundreds of thousands of samples simultaneously. In contrast to standard clinical testing, where one person's sample is tested in a single tube, mass testing labels each person's sample with a unique piece of DNA that acts as a molecular barcode, then pools multiple samples together so that they can be jointly tested. DNA sequencing is then used to detect those samples with virus in the pool of hundreds of thousands of individuals, and assign the virus to the samples it came from on the basis of the molecular barcodes. A bench top sequencer can process tens of thousands a day. A larger machine generates enough sequence to run up to hundreds of thousands of tests in one day. Our aim is to make it possible for a moderately well-equipped molecular biology laboratory to be able to process tens of thousands of samples without much investment. We have successfully deployed SwabSeq testing at the high-complexity, CLIA-certified, UCLA SwabSeq COVID19 Testing laboratory. Our work has demonstrated the utility for high-throughput asymptomatic testing and with additional improvements can increase testing capacity by orders of magnitude, making it possible to deploy testing on a population scale. Our sequencing-based approach can be extended to also detect viral variants at the same time and to other viral pathogens. Mass testing will f nd asymptomatic carriers and thus inform public health policies so that containment of infection will be effective.",,2028,University Of California Los Angeles,573456,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P21537,1R21AI179550-01,Feasibility of conducting HIV surveillance in community wastewater,"PROJECT SUMMARY At the start of the COVID-19 pandemic in late 2019, an estimated 1.2 million peopleâ€Â""including 158,500 (13%) with undiagnosed infectionâ€Â""were living with HIV in the United States. Since then, HIV control efforts have been complicated by disruptions to HIV testing, care-related services, and case surveillance activities in state and local jurisdictions. However, the full impact of the COVID-19 pandemic on HIV transmission, incidence and outcomes has been difficult to quantify. Wastewater-based epidemiology (WBE) is a non-invasive and unbiased surveillance approach that can be used to estimate infectious disease occurrence in the population by detecting pathogen DNA or RNA in pooled community samples of wastewater. Here we propose to apply a novel WBE HIV surveillance method to measure HIV-1 nucleic acids in wastewater to estimate HIV incidence in sewersheds during the COVID-19 pandemic. This research study will pursue three specific aims: (1) to develop and validate a quantification method for HIV-1 nucleic acids (RNA and DNA) in urine, feces and wastewater settled solids, (2) in 30 people living with HIV, to c orrelate HIV nucleic acid (RNA and DNA) shedding in urine and feces with plasma viral load, and (3) using archived samples of wastewater rom Santa Clara and San Francisco Counties during the COVID pandemic, to determine trends in wastewater HIV-1 nucleic acid levels and compare findings with community case rates of HIV. The overarching goal of this project is to establish an HIV quantification method for wastewater-based surveillance using digital droplet, reverse transcription-PCR analysis that can be used to monitor HIV in the community. We hypothesize that wastewater surveillance can identify populations disproportionately affected by HIV, facilitating allocation of resources to those at highest risk, thereby maximizing HIV control. Investigating rates of changes in HIV nucleic acid in wastewater in relation to COVID-19 may also improve our understanding of how pandemic disease and its control strategies can impact HIV surveillance and patient care. Knowledge gained from this project will help establish a framework for wastewater-based surveillance for HIV in the US and globally that can reduce health disparities, improve health outcomes and prevent HIV transmission.",,2025,Stanford University,231713,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2023 +P21538,1RF1MH133427-01,The COVID-19 pandemic: Impact on mental health and HIV outcomes,"PROJECT SUMMARY Approximately half of all people with HIV (PWH) in the United States (US) have one or more mental health disorder. Ending the HIV Epidemic in the US requires addressing the mental health needs of, and improving HIV treatment outcomes for, PWH with mental health disorders. The goal of this project is to advance our understanding of the impact of the COVID-19 pandemic â€Â"" a disruption to HIV research and care â€Â"" on the mental health and HIV treatment outcomes of PWH in the US. The COVID-19 pandemic is a significant risk to mental health. Mental health symptoms among PWH have been exacerbated during the COVID-19 pandemic due to physical distancing restrictions, increased material hardship, decreased social support, concerns about COVID-19 exposure, infection and long COVID, and disruption to mental health services. Beyond symptoms, an important question remains unanswered: “Did COVID-19 increase the burden of diagnosed mental health disorders and/or psychiatric-related hospitalizations in PWH?” Mitigation policies to reduce the spread of SARS-CoV-2 led to restricted access to routine non-emergent healthcare, interfering with routine HIV monitoring and perhaps increasing hospitalizations particularly among PWH with mental health disorders, posing the question: “Was the frequency of unsuppressed HIV viral load and hospitalization different in PWH with (vs. without) diagnosed mental health disorders before and during the pandemic?” Our team consists of clinicians and epidemiologists with expertise in mental health, HIV, and COVID-19. We propose to leverage the research infrastructure of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), the largest and most diverse collaboration of longitudinal HIV cohorts in the US, to examine the COVID-19-related impact on mental health and HIV treatment outcomes. The specific aims for this 3-year project are: Aim 1: To examine trends and differences in the incidence rates of mental health diagnoses and psychiatric-related hospitalizations among PWH in the US before and during the COVID-19 pandemic. Aim 2. Aim 2. To evaluate the extent to which mental health- disparities in the rates of unsuppressed HIV viral load and all-cause hospitalization widened during the COVID-19 pandemic among PWH. This study directly addresses the priorities of the National Institute of Mental Health in the funding opportunity Urgent Award: COVID-19 Mental Health Research (PAR-22-113). Our aims will rapidly generate critical evidence of the impact of the COVID-19 pandemic on the mental health and HIV treatment outcomes among PWH in the US (overall and within 9 key subgroups), inform strategies to mitigate such impacts on PWH during and after the COVID-19 pandemic, and improve preparedness for future public health emergencies.",,2026,Johns Hopkins University,2035602,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P21540,1R21MD019394-01,Pandemic preparedness for underserved persons in the US: Harnessing data from the RADx-UP consortium to assess public health tools for resource allocation,"PROJECT ABSTRACT Pandemic preparedness requires strengthening surveillance for emerging viruses, but also a plan for public health response when the next pathogen rapidly infects humans on a global scale. In order to ensure that the disproportionate disability and death experienced among disadvantaged populations in the US does not repeat in a future pandemic, public health agencies will need to validate resource allocation and surveillance tools within a health disparities framework. The RADx-UP Consortium enables such as an evaluation, since this NIH-funded Consortium of over 130 projects, with over 370,000 nationwide participants, focused on improving test access, and eliciting COVID19 stress and vaccine perception among underserved persons. Using RADx- UP data as the ground truth, we will test whether three area level vulnerability indicesâ€Â""the Social Vulnerability Index, the Minority Health Social Vulnerability Index, and the Community Vulnerability Indexâ€Â""identify persons experiencing food or housing insecurity, or gaps in healthcare access during the pandemic (Aim 1). We will leverage methods from clinical trial literature to assess RADx-UP data generalizability. We will link to American Community Survey, and generate county-standardized estimates of pandemic stress and vaccine concerns for the more than 900 US counties with participants in the RADx-UP consortium. We will then assess the association of these standardized estimates with the three area level vulnerability indices. A second aim of the proposed work will be to assess the predictive performance of the promising tool of wastewater surveillance among underserved populations. We will link RADx-UP data with the publicly available National Wastewater Surveillance System data, and compare wastewater infection prevalence metrics with the test positivity rate among RADx-UP performed tests, and county-level hospitalizations and deaths. We will evaluate changes in predictive performance over time (e.g., before versus after vaccine availability), and with integration of area- level vulnerability indices and other census demographic variables. With the ultimate aim of reducing health disparities in the future pandemic, our team of epidemiologists, statisticians, nephrology and infectious disease clinicians, and health policy experts will evaluate existing and emerging pandemic preparedness tools. In doing so, we hope to promote a public health infrastructure responsive to groups most vulnerable to the health and social turbulence inherent to a pandemic.",,2025,Stanford University,231600,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Vulnerable populations unspecified | Other | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Research to inform ethical issues in the Allocation of Resources | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Approaches to public health interventions | Indirect health impacts | Social impacts",2023 +P21541,5R01AI148663-05,Intersection Between Viral Translation and Innate Immunity in the Context of Filovirus Infection,"The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) are negative-sense RNA viral pathogens that cause periodic outbreaks of severe disease in humans. Despite their importance as emerging pathogens and as public health threats, many aspects of filovirus biology remain understudied. One major knowledge gap concerns the function(s) of the non-protein coding sequences present in filovirus genomes that correspond to 5’ and 3’ untranslated regions (UTRs) in viral mRNAs. These sequences comprise ~22% of the MARV genome and a similar amount of the EBOV genome and yet have been barely studied. Another knowledge gap concerns mechanisms by which viral mRNAs are translated to protein and how this may be sustained when innate immune responses are activated. Beginning to address this, we previously demonstrated a role for an upstream open reading frame (uORF), present in the 5’UTR of the EBOV L open reading frame (ORF), in the regulation of L translation. We further implicated this uORF as providing a means to sustain L expression under conditions innate antiviral defenses are activated. These data support a role for the UTRs as translational regulators which can modulate viral gene expression in the face of innate antiviral defenses. Our recent profiling of MARV 3’UTR function suggests negative-regulatory elements are present in the nucleoprotein (NP) mRNA and that positive regulatory elements are present in the L mRNA. In addition, we previously reported that the MARV genome appears to be edited by adenosine deaminase activity, particularly in sequences corresponding to the nucleoprotein (NP) mRNA 3’UTR. We now show that such mutations substantially increase mRNA translation efficiency, suggesting a means to maintain NP expression when the IFN-induced p150 form of adenosine deaminase acting on RNA 1 (ADAR1) is upregulated. Interestingly, the regulatory elements within the wildtype NP 3’UTR are also capable of triggering innate immune responses, but this immune stimulating activity is alleviated by the presumptive ADAR1 editing mutations. To follow up on these observations, we propose a combination of transfection- and live virus-based experiments to define the translation regulatory elements in MARV and EBOV 3’ UTRs and to determine how ADAR1 editing impacts viral gene expression and virus replication. We will fully evaluate the capacity of MARV and EBOV 5’ and 3’UTRs to trigger innate antiviral responses, defining the sensors responsible for this induction. Finally, we will create recombinant MARVs with wildtype and mutant 3’UTR sequences. These will be tested in wildtype and ADAR1-deficient cells and mice in order to determine how translational regulatory elements and ADAR1 editing impact viral growth and pathogenesis. Cumulatively, these studies will provide significant new insight into filovirus-host interactions related to translation and innate immune evasion.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,619478,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P21542,5R44AI172551-02,"PANDAA for universal, pan-lineage molecular detection of filoviruses to enable rapid epidemic response.","Ebolavirus [EBOV] and Marburgvirus [MARV] are filoviruses that cause severe hemorrhagic fevers in humans and primates and are listed among the urgently concerning pathogens prioritized in the WHO R&D Blueprint. Genomic sequences of the EBOV and MARV genera differ by >55%, and within each genera the species sequence diversity threshold is >23% thus detection by gold standard qPCR-based methods has been encumbered by significant genetic variability between filoviruses. Clinical diagnosis of EBOV and MARV is difficult as the early stages (i.e., pre- hemorrhagic) present with non-specific symptoms associated with a range of febrile illnesses that are displayed by other infectious agents endemic to affected areas e.g., malaria, yellow fever, dengue fever, Crimean-Congo hemorrhagic (CCHFV) or Lassa fevers. In order to isolate infected individuals, effective control during an EBOV or MARV outbreak can only be achieved by implementing rapid and accurate diagnostics with consistently reliable performance. Aldatu has pioneered the use of PANDAA technology, which enables probe-based qPCR for target detection in highly variable genomic regions by simultaneously adapting and amplifying diverse templates. PANDAA uniquely mitigates the presence of genetic polymorphisms to allow otherwise divergent templates to be detected by fluorescent probes. As such, PANDAA-enabled qPCR is an ideal solution for universal detection of pathogens with significant strain, lineage, and/or sub-type sequence diversity. Aldatu is uniquely positioned to deliver a rapid pan- filovirus qPCR-based assay that is rapid, sensitive molecular diagnostic for the detection and differentiation of EBOV and MARV with superior performance compared to existing diagnostics and won’t be affected by genetic changes in new viral variants. PANDAA has been successfully applied to subtype-independent detection of more than fifteen drug resistance mutation (DRM) targets in HIV. Recently, we developed the first pan-lineage assay for Lassa fever virus (LASV), another WHO priority pathogen with high outbreak potential. We propose to leverage the unique capabilities of PANDAA to develop a rapid, sensitive molecular diagnostic assay for filovirus detection, and the first with pan-species coverage of EBOV and MARV, through the following specific aims: (1) development of a pan- filovirus PANDAA assay, leveraging proven techniques and proprietary PANDAA reagent design; (2) analytical validation including confirmation of species inclusivity and high specificity; (3) multiplexing of the PANDAA-Filovirus assay with existing assays for LASV and CCHFV to produce a viral hemorrhagic fever (VHF) panel, including the thermostabilization of the both PANDAA-Filovirus and PANDAA-VHF assays, to meet the requirements of diagnostics targeted to LMICs; (4) GMP manufacturing of the thermostabilized PANDAA-Filovirus and PANDAA-VHF assays and (5) assay validation using samples representing a broad variety of circulating species and geographies, with multi- site evaluations of the test kits at reference labs at CDC- and WHO-affiliated partner institutions. As the first pan- filovirus assay, we will provide a rapid, standardized testing option for all regions that can be deployed using pre- existing qPCR equipment in central labs to radically improve the diagnostic workflow and epidemic preparedness.",,2025,"ALDATU BIOSCIENCES, INC.",931246,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P21543,1R21AI175849-01,Role of Host Filamin Proteins in Regulating Filovirus Entry and Egress,"Filoviruses (Ebola [EBOV] and Marburg [MARV]) are zoonotic, emerging pathogens that cause sporadic and global outbreaks of severe hemorrhagic fever in humans and non-human primates. As EBOV and MARV can establish persistent infections in the CNS, semen, eye, and other immunologically privileged sites inaccessible to antibody therapy, and their re-emergence can result in long-term sequelae and death, understanding of host defense mechanisms that could lead to the development of new antiviral therapies is more critical than ever. Our lab is at the forefront of identifying host proteins that interact both physically and functionally with the filovirus VP40 matrix protein, the driving force for virus assembly and egress, to regulate these late stages of virus replication. To better understand the functional filovirus-host interactome, our laboratory has focused on direct interactions between the PPxY Late (L) domain motif conserved in the VP40 proteins of EBOV (eVP40) and MARV (mVP40) and modular WW-domains from select host proteins. In addition to positive regulators of filovirus egress, we have recently identified WW-domain interactors that negatively regulate VP40-mediated budding, including YAP/TAZ, BAG3, and WWOX. While the impact of these negative regulators is likely multifactorial and complex, we have made the intriguing observation that filamin B, a common downstream effector of YAP/TAZ and BAG3, acts as a potential dual regulator of live EBOV/MARV infectivity/entry and live EBOV/MARV egress. As dual role regulation of key stages at opposite ends of the filovirus lifecycle is novel and unexpected, the ultimate goal of this proposal is to determine how host protein filamin B mechanistically impacts the filovirus lifecycle. Filamins are a family of actin crosslinking/stabilizing proteins that regulate actin dynamics at the plasma membrane to control cell migration and morphology, vesicle trafficking, macropinocytosis, and cell division. Notably, macropinocytosis macropinosomes is (MPs) that are densely coated with actin, filamin, and filamin-associated proteins a key entry pathway for filoviruses, as these viruses enter the cell in vesicles termed . In addition, filamins are linked to cellular processes that mimic virion formation and/or egress such as filopodia formation, cell migration, and cytokinesis. Thus, we hypothesize that filamin B regulates infectivity/entry of filoviruses through effects on macropinocytosis, and regulates filovirus budding through effects on egress of filopodia-like filovirus particles. In this exploratory proposal, we propose to investigate the mechanisms by which filamin regulates filovirus infectivity/entry (Aim 1) and egress (Aim 2). Results from these studies will impact the field by identifying a novel host protein(s) whose expression modulates two critical and opposite steps in the filovirus lifecycle; entry and exit, as well as providing a better fundamental understanding of the functional filovirus-host interactome and host defense mechanisms that could lead to the development of new antiviral therapies.",,2025,University Of Pennsylvania,268250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21544,5R21AI167369-02,Dissecting the mechanisms of intestinal epithelial injury by Ebola virus using iPSC-derived intestinal organoids,"Project Summary Filoviruses, including ebola- and marburgviruses, are prime examples of zoonotic viruses that cause severe disease in humans. The most pathogenic ebolavirus species is Ebola virus (Zaire ebolavirus; EBOV) with case fatality rates ranging from 40 to 90%. Many patients who succumb to the disease are admitted to Ebola treatment units when they are already severely ill. Importantly, there are no therapeutics available to mitigate late-stage Ebola Virus Disease (EVD). While many aspects of EBOV pathogenesis have been extensively studied in cell culture systems and animal models, the involvement of the intestine in EVD is not at all understood, despite diarrhea being among the most frequent symptoms (78% of patients in some case studies) and being one of the main causes for demise. Gastrointestinal manifestations, including vomiting, abdominal pain, and diarrhea, are also common symptoms of Marburg virus (MARV) disease. There are currently no infection models available that allow to study the consequences of filovirus infection of the gut. To fill this gap, we propose to establish human intestinal infection platforms to dissect the molecular mechanisms underlying filovirus-induced damage of the intestinal organs. We will explore two potential mechanisms that might play a role in the pathophysiological effects induced by filovirus infection: i) Filovirus infection of the human intestinal epithelium leads to loss of barrier integrity. ii) Filovirus infection of the human intestinal epithelium modulates the function of ion transporters. Identifying mechanisms that contribute to the induction of severe diarrhea in filovirus infection has the potential to inform urgently needed therapeutic approaches to mitigate the severe intestinal symptoms in late-stage filovirus disease. Human induced pluripotent stem cells (iPSCs) are capable of indefinite self-renewal and have the potential to differentiate into any tissue-specific cell lineage, including human intestinal organoids (HIOs). In preparation for this project, we have successfully achieved robust EBOV and MARV infections of iPSC-derived HIOs. The infected cells showed signs of cell damage, and transcriptomics analysis indicated the modulation of cell junction pathways and a set of ion transporters known to play a role in the induction of diarrhea. To begin to explore the intrinsic host response of intestinal cells to filovirus infection and the impact of infection-induced cellular damage on barrier integrity, we have designed the following specific aims: Specific Aim 1: To study the pathophysiological effects of EBOV and MARV infection on intestinal epithelial integrity. Specific Aim 2: To validate the role of individual genes by genetic ablation and test potential drug candidates as modulators of intestinal epithelial function.",,2024,BOSTON MEDICAL CENTER,212500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P21545,5R41AI172464-02,"Development of Host- Oriented Therapeutics Targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2),","The ultimate goal of this Phase I application is to discover and develop host-oriented small molecule compounds targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 is a novel coronavirus driving the current global pandemic of severe respiratory syndrome in humans. Antiviral therapeutics are urgently needed to combat infection by SARS-CoV-2 and new variants that are continuing to emerge. We have discovered several chemical series that target modular interactions between specific host proteins containing WW-domains (e.g. Nedd4) and viral proteins containing PPxY motifs (e.g. Ebola VP40). Notably, emerging RNA virus pathogens such as Ebola, Marburg, Lassa, and rabies viruses all encode PPxY motifs that recruit host WW-domain containing proteins to facilitate efficient virus egress, spread, and transmission. Interestingly, the surface-exposed Spike glycoprotein (S) of SARS-CoV-2 also has a putative WW-domain binding motif (25PPAY28), that is not present in the S protein of SARS-CoV-1 or more attenuated coronavirus strains. The acquisition of this PPAY motif in the major surface protein of SARS-CoV-2 virions raises the intriguing possibility that it may contribute to the unique pathogenicity and/or transmission of SARS-CoV-2 via interactions with specific host WW-domain bearing proteins. In our ongoing studies on filoviruses and arenaviruses, we have used extensive SAR to identify a lead compound series capable of blocking egress and spread of live EBOV, MARV, and LAFV in cell culture, as well as blocking disease progression in vivo in a live MARV challenge model. Here, we hypothesize that “informed” SAR analyses of our in-hand PPxY/WW-domain inhibitors (e.g. lead candidate FC-10696) will lead to the discovery of analogs capable of blocking egress and disease progression of SARS-CoV-2, as well as related PPxY-containing variants that may emerge in the future. In support of our hypothesis, we present strong preliminary data showing that the PPxY motif within the S protein of SARS-CoV-2 virus can interact with host WW-domain containing proteins that are known to promote egress and spread of EBOV, MARV, and LAFV. Moreover, our current lead candidate PPxY budding inhibitors show activity in blocking egress of live SARS-CoV-2 virus infection in human lung epithelial cells. In this Phase I proposal, we will identify and evaluate host-oriented inhibitors as potential therapeutics for SARS-CoV-2 and related coronaviruses by combining the pharmaceutical and medicinal chemistry expertise of the scientists at the Fox Chase Chemical Diversity Center, Inc. (FCCDC) with the expertise and experience of the Harty Lab at the University of Pennsylvania in the experimental aspects of virus-host interactions and antiviral therapy, and the lab of Olena Shtanko at Texas Biomedical Research Institute for evaluating compounds against live viruses under BSL-3 conditions. The three aims are (1) lead finding and optimization medicinal chemistry including ADME profiling, (2) evaluation for the ability to specifically inhibit egress of SARS-CoV-2 VLPs and PPxY- mediated S-host protein interactions, and (3) in vitro and in vivo analyses against authentic SARS-CoV-2 virus.",,2024,"FOX CHASE CHEMICAL DIVERSITY CENTER, INC",292428,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21546,5R01AI158220-03,Computational and Biophysical Analysis of the Filovirus Matrix Protein System,"Project Summary Ebola (EBOV) and Marburg (MARV) filoviruses cause severe hemorrhagic fever in humans with up to 90% mortality rates. Their genome contains only seven genes including the viral matrix protein VP40 which, when expressed in mammalian cells, is sufficient to produce virus-like particles (VLPs) that are essentially indistinguishable from live virions. VP40 forms dimers, hexamers and octamers mediated by different protein-protein (PPI) and protein-lipid (PLI) interactions that fulfill different and essential roles in the viral lifecycle, making VP40 a “swiss army knife” of proteins. The fascinating dynamic equilibria of VP40 and the availability of VLPs as a model system for direct observations outside of a BSL4 laboratory make VP40 a unique system to rigorously study the biophysical basis for viral budding as well as PPIs and PLIs in general. The significance of these studies is further increased because VP40 is the most conserved protein upon virus passage through humans, but exploiting VP40 as a potential drug target is unlikely to succeed without understanding the physical basis for oligomerization and function of VP40. The Stahelin and Wiest laboratories, building on established collaborations with each other and several other collaborators supplying specific expertise, will use computational, experimental and structural biophysics methods to investigate the central hypothesis of this grant: that interdomain interactions of VP40 are key regulators of VP40 structures during the viral life cycle. In two specific aims, we will (i) Determine the biophysical mechanisms by which VP40 dimer, hexamer and octamers form in silico, in vitro and in human cells and (ii) determine how mutations of VP40 that arise in humans during the course of an outbreak as well as in animals during passage of virus contribute to VP40 conformational change and rearrangement into its separate oligomeric forms. These questions will be studied using a tightly integrated approach using multiscale molecular dynamics simulations on the Ã'µs timescale and free energy perturbation methods on the computational side and hydrogen-deuterium exchange, cellular imaging of VLPs as well as more traditional biophysical experiments such as ultracentrifugation and SPR to determine the binding constants of wildtype VP40 from EBOV and MARV as well as pertinent mutants. This innovate and integrated approach will not only provide careful validation of the results, but also provide detailed insights into the PPIs and PLIs governing the oligomerization equilibria across many time- and lengths scale, thus enabling a rigorous understanding of the biophysical principles for a biomedically very important filovirus protein that will have a significant impact on understanding other PPIs and PLIs.",,2026,Purdue University,708064,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P21547,5R21AI169535-02,Functional Characterization of Egyptian rousette Bat Innate immune synapses,"The long-term goal is to characterize the cellular and molecular constituents of the bat immune system. Our group had been working on Marburg virus (MARV) spillover and transmission from Egyptian rousette (ERB, Rousettus aegyptiacus) bats. The ultimate goal of One Health pathogen surveillance programs is the identification of the most likely source of pathogen spillovers, and the practices more likely to facilitate the barrier jump. After this, the fate of emergence depends on the pathogen ability to transmit within humans. Our central hypothesis is that the immunological differences between the zoonotic host and humans are a significant determinant of the frequency of spillovers. After a detailed genome comparison, we reported multiple immune-related gene families that have undergone expansion in ERB compared to humans: the expansion of natural Killer Lectin-like Receptor-C (KLRC or NKG2) and KLR-D (or CD94) gene families, MHC Class I genes and type I interferon -ω and -α. Later, we revealed an increase in copy number of IGHV genes known to act in viral protection in humans; a duplication of functional IgE genes with different tissue expression patterns and theoretical functions; distinctive putative functions and structural characteristics of the four IgGs; lack of expansion of FcR for IgG (FcγR) compared to primates and potential different functionality; and the complete absence of functional short pentraxins. All these observations indicate that ERB establishes a tolerogenic state to deal with pathogen infection. Here, we propose to functionally characterize ERBs unique NK and IFN immunological synapses. The objective of this proposal is to confirm experimentally the predicted genomic functionality. The rationale is that Tolerance could be the basis for the unusual resilience of bats to withstand viral infections that are highly virulent and/or lethal in humans. The central hypothesis will be tested by pursuing 2 specific aims: 1) To determine the NKG2-CD94 association potential to form a functional receptor and the signaling downstream of the heterodimers to evaluate ERB NK activation mechanisms.; 2) To determine functionality and signaling cascade downstream ERBs Type I IFNs to test whether the expansion of IFN -ω and -α correlates with biological differences. We will pursue them using an innovative combination of immunological techniques that take advantage from NIAID investments in the Atlas of Immune Cells, and single- cell genomics as well as previous investments to generate ERB specific reagents. This research is significant, because it will advance knowledge at the crucial interphase that determine transmission and pathogenesis if the differences between the immunological status of different mammals are a driver for zoonotic spillovers. The proximate expected outcome of this work is an understanding of the particularities of the bat innate immunological system and an assessment of its baseline status. The results will have an immediate positive impact on the studies on MARV spillover. Moreover, as other bat immunological systems are similarly characterized, this work will lay the groundwork to assess bats immunological features.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,211250,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector biology",2022 +P21548,1R43AI179343-01,Development of antibody drug conjugates as pan-filo antivirals,"Project Summary Filoviruses cause severe hemorrhagic fevers and are among the deadliest human viruses with no approved treatment or prophylactic options. Periodic outbreaks, such as the recent epidemic of Ebola virus (EBOV) in West Africa, exhibit mortality rates ranging from 50-90%. They are classified as “Category A priority bioweapon agents” by the Centers for Disease Control and Prevention. The most advanced candidates for anti-filovirus therapy with proven efficacy in non-human primates (NHPs) utilize RNA interference (RNAi), high dose mixtures of monoclonal antibodies (mAbs), or repurposed influenza, herpes or hepatitis C inhibitors. Although they represent important advances, these approaches have serious limitations including the high therapeutic doses required (20-30 g of mAb/patient), limited spectrum (primarily Zaire ebolavirus) and/or narrow therapeutic windows (small molecules/RNAi). Building on recent work demonstrating the critical nature of endosomal interactions between the filoviral glycoprotein (GP) and the host cholesterol transport protein Niemann-Pick C1 (NPC1) for filoviral entry, we have developed antibodies and small molecules that disrupt this mechanism to inhibit viral entry. These include several bispecific GP-targeting pan-ebolavirus broadly neutralizing antibodies (bNAbs) efficacious in multiple animal models, with down-selection to a final cocktail based on NHP efficacy underway. In parallel, we identified a phenylpiperazine compound MBX-5321, which inhibits the GP-NPC1 interaction to block infections of virulent EBOV, SUDV and MARV at nM concentrations in vitro, demonstrates excellent PK/PD properties, exhibits excellent murine tolerability, has established efficacy in mice, and is currently being optimized for a targeted IND. In this proposal we will tether MBX-5321 to bispecific pan-filo bNABs to make broad-spectrum antibody-drug conjugates (ADCs) that synergistically inhibit viral entry. The objective of this proposal is to demonstrate that these ADCs will provide improved efficacy and selectivity for filovirus treatment over either agent alone, providing highly efficacious pan-filo agents, broadening the therapeutic window and easing drug stockpiling efforts. We will accomplish this objective through three specific aims: In Aim 1 we will synthesize and complete physical characterization of >40 ADCs demonstrating serum stability with efficient endosomal release. In Aim 2 we will prioritize ADCs through in vitro analysis of pan-filovirus inhibitory activity. In Aim 3 we prioritize ADCs for PK and toxicity and evaluate two pan-filovirus ADCs for in vivo efficacy in a mouse model of EBOV infection.",,2025,"MICROBIOTIX, INC",300000,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21549,1R44AI172551-01,"PANDAA for universal, pan-lineage molecular detection of filoviruses to enable rapid epidemic response.","Ebolavirus [EBOV] and Marburgvirus [MARV] are filoviruses that cause severe hemorrhagic fevers in humans and primates and are listed among the urgently concerning pathogens prioritized in the WHO R&D Blueprint. Genomic sequences of the EBOV and MARV genera differ by >55%, and within each genera the species sequence diversity threshold is >23% thus detection by gold standard qPCR-based methods has been encumbered by significant genetic variability between filoviruses. Clinical diagnosis of EBOV and MARV is difficult as the early stages (i.e., pre- hemorrhagic) present with non-specific symptoms associated with a range of febrile illnesses that are displayed by other infectious agents endemic to affected areas e.g., malaria, yellow fever, dengue fever, Crimean-Congo hemorrhagic (CCHFV) or Lassa fevers. In order to isolate infected individuals, effective control during an EBOV or MARV outbreak can only be achieved by implementing rapid and accurate diagnostics with consistently reliable performance. Aldatu has pioneered the use of PANDAA technology, which enables probe-based qPCR for target detection in highly variable genomic regions by simultaneously adapting and amplifying diverse templates. PANDAA uniquely mitigates the presence of genetic polymorphisms to allow otherwise divergent templates to be detected by fluorescent probes. As such, PANDAA-enabled qPCR is an ideal solution for universal detection of pathogens with significant strain, lineage, and/or sub-type sequence diversity. Aldatu is uniquely positioned to deliver a rapid pan- filovirus qPCR-based assay that is rapid, sensitive molecular diagnostic for the detection and differentiation of EBOV and MARV with superior performance compared to existing diagnostics and won’t be affected by genetic changes in new viral variants. PANDAA has been successfully applied to subtype-independent detection of more than fifteen drug resistance mutation (DRM) targets in HIV. Recently, we developed the first pan-lineage assay for Lassa fever virus (LASV), another WHO priority pathogen with high outbreak potential. We propose to leverage the unique capabilities of PANDAA to develop a rapid, sensitive molecular diagnostic assay for filovirus detection, and the first with pan-species coverage of EBOV and MARV, through the following specific aims: (1) development of a pan- filovirus PANDAA assay, leveraging proven techniques and proprietary PANDAA reagent design; (2) analytical validation including confirmation of species inclusivity and high specificity; (3) multiplexing of the PANDAA-Filovirus assay with existing assays for LASV and CCHFV to produce a viral hemorrhagic fever (VHF) panel, including the thermostabilization of the both PANDAA-Filovirus and PANDAA-VHF assays, to meet the requirements of diagnostics targeted to LMICs; (4) GMP manufacturing of the thermostabilized PANDAA-Filovirus and PANDAA-VHF assays and (5) assay validation using samples representing a broad variety of circulating species and geographies, with multi- site evaluations of the test kits at reference labs at CDC- and WHO-affiliated partner institutions. As the first pan- filovirus assay, we will provide a rapid, standardized testing option for all regions that can be deployed using pre- existing qPCR equipment in central labs to radically improve the diagnostic workflow and epidemic preparedness.",,2025,"ALDATU BIOSCIENCES, INC.",964499,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P21550,5R01AI148663-04,Intersection Between Viral Translation and Innate Immunity in the Context of Filovirus Infection,"The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) are negative-sense RNA viral pathogens that cause periodic outbreaks of severe disease in humans. Despite their importance as emerging pathogens and as public health threats, many aspects of filovirus biology remain understudied. One major knowledge gap concerns the function(s) of the non-protein coding sequences present in filovirus genomes that correspond to 5’ and 3’ untranslated regions (UTRs) in viral mRNAs. These sequences comprise ~22% of the MARV genome and a similar amount of the EBOV genome and yet have been barely studied. Another knowledge gap concerns mechanisms by which viral mRNAs are translated to protein and how this may be sustained when innate immune responses are activated. Beginning to address this, we previously demonstrated a role for an upstream open reading frame (uORF), present in the 5’UTR of the EBOV L open reading frame (ORF), in the regulation of L translation. We further implicated this uORF as providing a means to sustain L expression under conditions innate antiviral defenses are activated. These data support a role for the UTRs as translational regulators which can modulate viral gene expression in the face of innate antiviral defenses. Our recent profiling of MARV 3’UTR function suggests negative-regulatory elements are present in the nucleoprotein (NP) mRNA and that positive regulatory elements are present in the L mRNA. In addition, we previously reported that the MARV genome appears to be edited by adenosine deaminase activity, particularly in sequences corresponding to the nucleoprotein (NP) mRNA 3’UTR. We now show that such mutations substantially increase mRNA translation efficiency, suggesting a means to maintain NP expression when the IFN-induced p150 form of adenosine deaminase acting on RNA 1 (ADAR1) is upregulated. Interestingly, the regulatory elements within the wildtype NP 3’UTR are also capable of triggering innate immune responses, but this immune stimulating activity is alleviated by the presumptive ADAR1 editing mutations. To follow up on these observations, we propose a combination of transfection- and live virus-based experiments to define the translation regulatory elements in MARV and EBOV 3’ UTRs and to determine how ADAR1 editing impacts viral gene expression and virus replication. We will fully evaluate the capacity of MARV and EBOV 5’ and 3’UTRs to trigger innate antiviral responses, defining the sensors responsible for this induction. Finally, we will create recombinant MARVs with wildtype and mutant 3’UTR sequences. These will be tested in wildtype and ADAR1-deficient cells and mice in order to determine how translational regulatory elements and ADAR1 editing impact viral growth and pathogenesis. Cumulatively, these studies will provide significant new insight into filovirus-host interactions related to translation and innate immune evasion.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,619478,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21551,5R21AI153815-02,Role of Host Angiomotin as a Central Regulator of Filovirus Egress and Dissemination,"Filoviruses (Ebola [EBOV] and Marburg [MARV]) and arenaviruses (e.g. Lassa virus; LAFV) are zoonotic, emerging pathogens that cause outbreaks of severe hemorrhagic fever in humans and non-human primates. A fundamental understanding of the virus-host interface is critical for developing future strategies and countermeasures for therapeutic intervention. As the filovirus VP40 and LAFV Z matrix proteins drive virion assembly and egress, in part, by hijacking specific host proteins containing WW-domains that can interact with their highly conserved PPxY L-domain motifs, these interactions represent a novel therapeutic target to inhibit egress and dissemination of these hemorrhagic fever viruses. Our early studies to identify host WW-domain proteins that regulate filovirus and arenavirus budding identified the E3 ubiquitin ligases Nedd4, ITCH, and WWP1 as positive regulators of viral PPxY-mediated budding. However, in more recent studies, we identified WW-domain containing proteins YAP/TAZ, BAG3, and now WWOX (WW Domain Containing Oxidoreductase; a multi-functional tumor suppressor), as negative regulators of PPxY-mediated egress of VP40 and Z VLPs. The identification of YAP/TAZ, BAG3, and WWOX as negative regulators of viral PPxY-mediated budding is particularly intriguing since all three of these proteins interact with Angiomotin (Amot), a multi-PPxY containing protein that functions as a “master regulator” of Hippo pathway (YAP/TAZ) signaling, cytoskeletal dynamics, cell migration/proliferation, and tight junction (TJ) integrity. Moreover, expression and stability of Amot itself are regulated by PPxY/WW-domain interactions with the Nedd4 family of E3 ubiquitin ligases. Thus, we hypothesize that Amot is a central interactor linking both the positive and negative WW-domain containing regulators of virus egress, and that modular mimicry between viral and host PPxY motifs and the competitive nature of their binding to the same host WW-domain containing proteins will have a major impact on both cellular processes and viral replication and pathogenesis. Indeed, we were first to report that expression of endogenous Amot positively regulates PPxY-mediated egress of EBOV and MARV VP40 VLPs as well as egress and spread of live EBOV and MARV in cell culture. In this proposal, we will build upon our novel finding that PPxY-containing Amot can positively regulate egress and spread of PPxY-containing viruses including EBOV and MARV, and determine whether the competitive PPxY/WW-domain interplay among VP40/Z â€Â"" Amot â€Â"" host WW-domain interactors regulates egress of VLPs and live viruses in vitro and in vivo. Successful completion of these aims will provide novel insights into how this complex network of modular PPxY/WW-domain interactions with Amot impacts late stages of hemorrhagic fever virus egress and dissemination and serve as proof-of principle for therapeutic strategies targeting an essential viral-host interaction that may represent an Achilles heel for numerous RNA viruses.",,2024,University Of Pennsylvania,225313,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21552,5R44AI157593-02,Thermostabilized Subunit Glycoprotein Vaccine Platform: Immune Characterization of an Emulsified Adjuvant with SARS-CoV-2 Spike Protein and EBOV GP,"7. Project Summary/Abstract The proposal requests funding to support manufacturing and immune characterization of a novel, emulsified adjuvant which is uniquely compatible with lyophilization strategies to enable thermostabilization of glycoprotein vaccines. The major objectives of the study are to transfer and optimize the manufacture of a novel adjuvant and to characterize and assess the comparative immunogenicity of different adjuvant formulations in terms of both humoral and cell mediated immunity, utilizing two different multimeric glycoprotein antigens. Ultimately, this program will identify an optimal adjuvant formulation, capable of potentiating both humoral and cell mediated immunity to protein antigens, compatible with lyophilization and resulting in a thermostabilized vaccine utilizing Generally Regarded as Safe (‘GRAS’) excipients. Specific formulation development will be done in the context of the Zaire ebolavirus (EBOV) GP, a component of our trivalent filovirus vaccine (TriFiloVax) targeting EBOV, Sudan ebolavirus (SUDV) and marburgvirus (MARV) and with SAR-CoV-2 spike protein, supporting COVID-19 vaccine development efforts. While state of the art medical treatment may increase the chances of survival of both the highly fatal EBOV and the highly transmissible COVID-19, currently no antiviral therapy is available to prevent or cure the disease. Vaccination remains the most feasible route for addressing and preventing future epidemics. Ongoing clinical development in the context of EBOV has identified both therapeutics and vaccines which are being tested in the ongoing outbreak in the Democratic Republic of Congo. However, these approaches are highly selective for EBOV only. The sole approved vaccine is a virally vectored vaccine requiring cold storage (<-60Ã'°C) storage / distribution and also cannot be used in at-risk populations showing any signs of immunodeficiency or in pregnant women and is potentially more variable in less responsive populations. These vaccine platforms also may not be used repeatedly (either as boosters or with other protein antigens) because of the humoral induced immunity to the viral platform which occurs with vaccination. There is no vaccine for MARV, SUDV or COVID-19. In contrast, subunit vaccines offer many advantages, including improved safety, compatibility with immunosuppressed, immunocompromised or high risk populations or those who have previously received virally vectored vaccines. Thermostabilized formulations also facilitate stockpiling and emergency use in logistically challenging environments. The specific aims of the proposal include to i) transfer manufacturing methods and manufacture engineering lots of CoVaccine with varying Polysorbate 80 content and ii) characterize the enhancement of both humoral and cell mediated immunity by CoVaccine HTâÂ""¢ with SARS-CoV-2 Spike protein and EBOV GP, thereby facilitating the development of TriFiloVax (for EBOV, MARV and SUDV) and CiVax (for COVID-19) and more generally for other protein vaccines.",,2023,"SOLIGENIX, INC.",829746,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine logistics and supply chains and distribution strategies,2020 +P21553,1R21AI167369-01A1,Dissecting the mechanisms of intestinal epithelial injury by Ebola virus using iPSC-derived intestinal organoids,"Project Summary Filoviruses, including ebola- and marburgviruses, are prime examples of zoonotic viruses that cause severe disease in humans. The most pathogenic ebolavirus species is Ebola virus (Zaire ebolavirus; EBOV) with case fatality rates ranging from 40 to 90%. Many patients who succumb to the disease are admitted to Ebola treatment units when they are already severely ill. Importantly, there are no therapeutics available to mitigate late-stage Ebola Virus Disease (EVD). While many aspects of EBOV pathogenesis have been extensively studied in cell culture systems and animal models, the involvement of the intestine in EVD is not at all understood, despite diarrhea being among the most frequent symptoms (78% of patients in some case studies) and being one of the main causes for demise. Gastrointestinal manifestations, including vomiting, abdominal pain, and diarrhea, are also common symptoms of Marburg virus (MARV) disease. There are currently no infection models available that allow to study the consequences of filovirus infection of the gut. To fill this gap, we propose to establish human intestinal infection platforms to dissect the molecular mechanisms underlying filovirus-induced damage of the intestinal organs. We will explore two potential mechanisms that might play a role in the pathophysiological effects induced by filovirus infection: i) Filovirus infection of the human intestinal epithelium leads to loss of barrier integrity. ii) Filovirus infection of the human intestinal epithelium modulates the function of ion transporters. Identifying mechanisms that contribute to the induction of severe diarrhea in filovirus infection has the potential to inform urgently needed therapeutic approaches to mitigate the severe intestinal symptoms in late-stage filovirus disease. Human induced pluripotent stem cells (iPSCs) are capable of indefinite self-renewal and have the potential to differentiate into any tissue-specific cell lineage, including human intestinal organoids (HIOs). In preparation for this project, we have successfully achieved robust EBOV and MARV infections of iPSC-derived HIOs. The infected cells showed signs of cell damage, and transcriptomics analysis indicated the modulation of cell junction pathways and a set of ion transporters known to play a role in the induction of diarrhea. To begin to explore the intrinsic host response of intestinal cells to filovirus infection and the impact of infection-induced cellular damage on barrier integrity, we have designed the following specific aims: Specific Aim 1: To study the pathophysiological effects of EBOV and MARV infection on intestinal epithelial integrity. Specific Aim 2: To validate the role of individual genes by genetic ablation and test potential drug candidates as modulators of intestinal epithelial function.",,2024,BOSTON MEDICAL CENTER,273750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P21554,1R41AI172464-01,"Development of Host- Oriented Therapeutics Targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2),","The ultimate goal of this Phase I application is to discover and develop host-oriented small molecule compounds targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 is a novel coronavirus driving the current global pandemic of severe respiratory syndrome in humans. Antiviral therapeutics are urgently needed to combat infection by SARS-CoV-2 and new variants that are continuing to emerge. We have discovered several chemical series that target modular interactions between specific host proteins containing WW-domains (e.g. Nedd4) and viral proteins containing PPxY motifs (e.g. Ebola VP40). Notably, emerging RNA virus pathogens such as Ebola, Marburg, Lassa, and rabies viruses all encode PPxY motifs that recruit host WW-domain containing proteins to facilitate efficient virus egress, spread, and transmission. Interestingly, the surface-exposed Spike glycoprotein (S) of SARS-CoV-2 also has a putative WW-domain binding motif (25PPAY28), that is not present in the S protein of SARS-CoV-1 or more attenuated coronavirus strains. The acquisition of this PPAY motif in the major surface protein of SARS-CoV-2 virions raises the intriguing possibility that it may contribute to the unique pathogenicity and/or transmission of SARS-CoV-2 via interactions with specific host WW-domain bearing proteins. In our ongoing studies on filoviruses and arenaviruses, we have used extensive SAR to identify a lead compound series capable of blocking egress and spread of live EBOV, MARV, and LAFV in cell culture, as well as blocking disease progression in vivo in a live MARV challenge model. Here, we hypothesize that “informed” SAR analyses of our in-hand PPxY/WW-domain inhibitors (e.g. lead candidate FC-10696) will lead to the discovery of analogs capable of blocking egress and disease progression of SARS-CoV-2, as well as related PPxY-containing variants that may emerge in the future. In support of our hypothesis, we present strong preliminary data showing that the PPxY motif within the S protein of SARS-CoV-2 virus can interact with host WW-domain containing proteins that are known to promote egress and spread of EBOV, MARV, and LAFV. Moreover, our current lead candidate PPxY budding inhibitors show activity in blocking egress of live SARS-CoV-2 virus infection in human lung epithelial cells. In this Phase I proposal, we will identify and evaluate host-oriented inhibitors as potential therapeutics for SARS-CoV-2 and related coronaviruses by combining the pharmaceutical and medicinal chemistry expertise of the scientists at the Fox Chase Chemical Diversity Center, Inc. (FCCDC) with the expertise and experience of the Harty Lab at the University of Pennsylvania in the experimental aspects of virus-host interactions and antiviral therapy, and the lab of Olena Shtanko at Texas Biomedical Research Institute for evaluating compounds against live viruses under BSL-3 conditions. The three aims are (1) lead finding and optimization medicinal chemistry including ADME profiling, (2) evaluation for the ability to specifically inhibit egress of SARS-CoV-2 VLPs and PPxY- mediated S-host protein interactions, and (3) in vitro and in vivo analyses against authentic SARS-CoV-2 virus.",,2024,"FOX CHASE CHEMICAL DIVERSITY CENTER, INC",306500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P21555,5R01AI158220-02,Computational and Biophysical Analysis of the Filovirus Matrix Protein System,"Project Summary Ebola (EBOV) and Marburg (MARV) filoviruses cause severe hemorrhagic fever in humans with up to 90% mortality rates. Their genome contains only seven genes including the viral matrix protein VP40 which, when expressed in mammalian cells, is sufficient to produce virus-like particles (VLPs) that are essentially indistinguishable from live virions. VP40 forms dimers, hexamers and octamers mediated by different protein-protein (PPI) and protein-lipid (PLI) interactions that fulfill different and essential roles in the viral lifecycle, making VP40 a “swiss army knife” of proteins. The fascinating dynamic equilibria of VP40 and the availability of VLPs as a model system for direct observations outside of a BSL4 laboratory make VP40 a unique system to rigorously study the biophysical basis for viral budding as well as PPIs and PLIs in general. The significance of these studies is further increased because VP40 is the most conserved protein upon virus passage through humans, but exploiting VP40 as a potential drug target is unlikely to succeed without understanding the physical basis for oligomerization and function of VP40. The Stahelin and Wiest laboratories, building on established collaborations with each other and several other collaborators supplying specific expertise, will use computational, experimental and structural biophysics methods to investigate the central hypothesis of this grant: that interdomain interactions of VP40 are key regulators of VP40 structures during the viral life cycle. In two specific aims, we will (i) Determine the biophysical mechanisms by which VP40 dimer, hexamer and octamers form in silico, in vitro and in human cells and (ii) determine how mutations of VP40 that arise in humans during the course of an outbreak as well as in animals during passage of virus contribute to VP40 conformational change and rearrangement into its separate oligomeric forms. These questions will be studied using a tightly integrated approach using multiscale molecular dynamics simulations on the Ã'µs timescale and free energy perturbation methods on the computational side and hydrogen-deuterium exchange, cellular imaging of VLPs as well as more traditional biophysical experiments such as ultracentrifugation and SPR to determine the binding constants of wildtype VP40 from EBOV and MARV as well as pertinent mutants. This innovate and integrated approach will not only provide careful validation of the results, but also provide detailed insights into the PPIs and PLIs governing the oligomerization equilibria across many time- and lengths scale, thus enabling a rigorous understanding of the biophysical principles for a biomedically very important filovirus protein that will have a significant impact on understanding other PPIs and PLIs.",,2026,Purdue University,708359,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P21556,5R21AI151483-02,Structure-Based Design of Peptide Entry Inhibitors against Ebola Virus Infection,"Abstract Ebola viruses (EBOV) along with Marburg viruses (MARV) belong to the Filoviridae family which infects humans and nonhuman primates and causes outbreaks with a high mortality up to 90%. We do not have approved drugs for treating this deadly viral disease and therefore it is urgent to develop therapeutics to cope with the dangerous outbreaks. In this project, we propose to develop peptide based inhibitors targeting the receptor binding site (RBS) to block viral infection. We will conduct structure based design using the available co-crystal structures of the NPC1 receptor or monoclonal antibodies bound to the viral glycoprotein. The initial evaluation will utilize pseudo- typed viruses to test viral entry in a cell based assay. The best peptide candidates from these assays will subsequently be tested in a BSL-4 containment facility using replication competent viruses for entry inhibition tests. In vivo evaluations of qualified candidates will be conducted in a virus challenge mouse model to measure protection efficacy. After all these evaluations, promising candidates could be advanced to nonhuman primates or human clinical trials.",,2024,University Of Nebraska Lincoln,209109,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21557,1R21AI169535-01,Functional Characterization of Egyptian rousette Bat Innate immune synapses,"The long-term goal is to characterize the cellular and molecular constituents of the bat immune system. Our group had been working on Marburg virus (MARV) spillover and transmission from Egyptian rousette (ERB, Rousettus aegyptiacus) bats. The ultimate goal of One Health pathogen surveillance programs is the identification of the most likely source of pathogen spillovers, and the practices more likely to facilitate the barrier jump. After this, the fate of emergence depends on the pathogen ability to transmit within humans. Our central hypothesis is that the immunological differences between the zoonotic host and humans are a significant determinant of the frequency of spillovers. After a detailed genome comparison, we reported multiple immune-related gene families that have undergone expansion in ERB compared to humans: the expansion of natural Killer Lectin-like Receptor-C (KLRC or NKG2) and KLR-D (or CD94) gene families, MHC Class I genes and type I interferon -ω and -α. Later, we revealed an increase in copy number of IGHV genes known to act in viral protection in humans; a duplication of functional IgE genes with different tissue expression patterns and theoretical functions; distinctive putative functions and structural characteristics of the four IgGs; lack of expansion of FcR for IgG (FcγR) compared to primates and potential different functionality; and the complete absence of functional short pentraxins. All these observations indicate that ERB establishes a tolerogenic state to deal with pathogen infection. Here, we propose to functionally characterize ERBs unique NK and IFN immunological synapses. The objective of this proposal is to confirm experimentally the predicted genomic functionality. The rationale is that Tolerance could be the basis for the unusual resilience of bats to withstand viral infections that are highly virulent and/or lethal in humans. The central hypothesis will be tested by pursuing 2 specific aims: 1) To determine the NKG2-CD94 association potential to form a functional receptor and the signaling downstream of the heterodimers to evaluate ERB NK activation mechanisms.; 2) To determine functionality and signaling cascade downstream ERBs Type I IFNs to test whether the expansion of IFN -ω and -α correlates with biological differences. We will pursue them using an innovative combination of immunological techniques that take advantage from NIAID investments in the Atlas of Immune Cells, and single- cell genomics as well as previous investments to generate ERB specific reagents. This research is significant, because it will advance knowledge at the crucial interphase that determine transmission and pathogenesis if the differences between the immunological status of different mammals are a driver for zoonotic spillovers. The proximate expected outcome of this work is an understanding of the particularities of the bat innate immunological system and an assessment of its baseline status. The results will have an immediate positive impact on the studies on MARV spillover. Moreover, as other bat immunological systems are similarly characterized, this work will lay the groundwork to assess bats immunological features.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,253500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Vector biology,2022 +P21558,5R21AI151732-02,Host factors and inhibition of Filoviruses,"Ebola virus (EBOV) and Marburg virus (MARV) are highly lethal hemorrhagic fever viruses of the Filoviridae family of viruses. Currently, there are no effective oral or easily scalable therapies for either virus. Both EBOV and MARV manifest vigorous anti-host evasion strategies focused on blocking the host antiviral interferon response. Both viruses interfere with host cell sensing of infection via their structural protein VP35, which inhibits viral dsRNA sensing and triggering of the host antiviral response. Therapeutic strategies that enhance host pathways that are inhibited by these viruses could therefore be of significant value. We have discovered that the well-tolerated FDA-approved oral anti-parasitic drug nitazoxanide (NTZ) inhibits infectious EBOV replication in human A549 cells in vitro. Furthermore, we find that NTZ enhances the RIG-I-like receptor (RLR) proteins retinoic-acid-inducible protein I (RIG- I) and Melanoma Differentiation-Associated protein 5 (MDA5), their common adaptor protein mitochondrial antiviral signaling protein (MAVS), the IFN-inducible double-stranded (ds) RNA sensor protein kinase R (PKR), and interferon signaling pathways. In addition, using deadCas9/CRISPR editing, we ablated RIG-I and PKR in A549 cells, and found that EBOV growth was significantly increased and in parallel NTZ's inhibitory effects were significantly attenuated. These results thus indicate that RIG-I and PKR are both required and non-redundant host restriction factors for EBOV. Moreover, PKR and RIG-I are both targeted by and necessary for NTZ's action indicating that NTZ counteracts the EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV infection. In Aim 1 of this proposal, we will test the hypothesis that NTZ also inhibits MARV in vitro, which we strongly expect given the importance of MARV's VP-35 protein in its pathogenesis. In Aim 1, we will also test our hypothesis that NTZ inhibits both EBOV and MARV in vivo in the guinea pig model. In Aim 2, we will test the impact of MDA5 or MAVS inhibition, in addition to studying RIG-I, PKR or GADD34 depletion on MARV replication. We will compare these results to experiments evaluating EBOV replication in monocytic THP-1 cells. These experiments will evaluate the role of these discrete sensors in NTZ's inhibitory effects upon EBOV and MARV and it will test the hypothesis that NTZ works through PKR and RIG-I in inhibition of MARV as it does in EBOV infection. Building on these studies, using an unbiased RNA-seq approach, we will determine transcriptomic signatures of cellular perturbations induced by NTZ in the setting of EBOV and MARV infection allowing us to define host immune regulatory circuits involved in cytoplasmic sensing of EBOV and MARV and the impact of NTZ. We anticipate that these studies will provide scientific underpinning for repurposing NTZ as a therapy for EBOV and MARV and uncover key innate immune molecules that control their pathogenesis.",,2023,BOSTON CHILDREN'S HOSPITAL,209375,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +P21559,7R21AI146682-03,Intrinsically-enhanced Ebola and Marburg virus like particles for increased potency and immune memory,"Summary This developmental project seeks to develop methods to dramatically boost immunogenicity of virus-like particle (VLP) vaccines. Ebola virus (EBOV) and Marburg virus (MARV) are members of the filovirus family of enveloped, negative-sense RNA viruses that causes outbreaks of severe human disease. Due to their lethality, filoviruses are among the handful of emerging viruses for which biosafety level 4 (BSL4) containment is required for their study. Although progress has been made toward EBOV vaccines, there remains a need for development of vaccines for other filoviruses, particularly MARV. VLPs are an often-explored vaccine platform for a variety of viruses, including for EBOV and MARV. Advantages of VLPs include their relative safety, as they cannot replicate and cause viral disease; their close resemblance to authentic virus, such that they present antigens in their native state; their capacity to elicit both B and T cell responses and their proven efficacy for a variety of systems. Potential challenges of VLPs as vaccines include relatively lower immunogenicity, as compared to live virus. Filovirus VLPs can be produced by co-expression of the viral matrix protein VP40, the viral glycoprotein (GP), with or without expression of the viral nucleoprotein (NP). Such VLPs have been demonstrated to stimulate dendritic cell (DC) responses, to elicit B and T cell mediated immunity and to protect mice, guinea pigs and non- human primates (NHPs) from lethal challenge. Therefore, filovirus VLPs are viable vaccine candidates. However, filovirus VLP immunogenicity is weak with protection requiring coadministration with an adjuvant and multiple doses. This is not ideal for vaccines that are mainly deployed in response to outbreaks. This application seeks to dramatically improve immunogenicity of EBOV and MARV VLPs by the rational incorporation of type I interferon (IFN) signaling domains from the cellular pattern recognition receptors RIG-I or TRIF into the particles. This enables delivery into cells of the IFN inducing domain by the VLPs, triggering robust innate immune responses reminiscent of live virus infection, to boost adaptive immune responses. To further pursue this direction, we will explore approaches to optimize the incorporation of IFN-inducing signaling domains into EBOV and MARV VLPs. We will then evaluate the capacity of the different enhanced VLP strategies to elicit B and T cell immune responses in vivo, and finally, test the most promising enhanced VLPs for the capacity to elicit rapid protection against EBOV and MARV challenge in mice. Successful completion of these studies will provide a novel platform for the development of filovirus vaccines and an approach that can likely be applied to other emerging viral pathogens.",,2023,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,230538,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21560,5U19AI142785-03,Research Project 1: Vaccine for Rapid Response to Filovirus Outbreak,"PROJECT SUMMARY/ABSTRACT â€Â"" Research Project 1 Ebola virus (EBOV) and Marburg virus (MARV) are filamentous enveloped non-segmented negative sense RNA viruses representing the two genera that comprise the family Filoviridae. The Marburgvirus genus contains one species (MARV), while the Ebolavirus genus is comprised of five recognized species: Sudan ebolavirus (SUDV), Zaire ebolavirus (EBOV), Tai Forest ebolavirus (TAFV), Reston ebolavirus (RESTV), and Bundibugyo ebolavirus (BDBV). These viruses are important human pathogens with case fatality rates ranging from 70% to 90% for EBOV, up to 90% for MARV, approximately 55% for SUDV, and 25-50% for BDBV. These agents are classified as Category A Priority Pathogens by the NIAID/NIH and CDC, and there are presently no licensed active or passive interventions for exposure resulting from natural outbreak, laboratory accident, or deliberate misuse. The public health concern is based on both the emerging infectious disease status of these viruses and their potential use as biologic weapons. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks in endemic areas of sub-Saharan Africa, with laboratory workers engaged in filovirus research, and with military and civilian personnel threatened by weaponized filoviruses. The ideal vaccine to meet both the outbreak and bioweapon scenarios would rapidly confer protection against all species of EBOV and MARV with a single dose. Among the vaccine strategies tested for single dose protection, the most successful have been vectored vaccines based on vesicular stomatitis virus (VSV). The progressing urbanization of sub-Saharan Africa has increased the probability that a filovirus infected individual will enter an area of high population density either unknowingly or to seek medical aid. As seen in the recent west African outbreak, the increased mobility within and between the urban centers can rapidly expand the number and geographic distribution of cases. Thus, in the absence of widespread prophylactic immunization, the most effective uses of a vaccine against the filoviruses will be protection of healthcare workers and breaking spread using `ring vaccination'. The first application is aided by, and the second application is dependent upon, a rapid onset of protection. Funded work under NIAID contract HHSN272201700077C supports development of vaccines for EBOV, SUDV, and MARV that are vectored with rVSVN4CT1, a live attenuated VSV vector that has proven safe in multiple clinical trials. This application proposes to develop an rVSVN4CT1-vectored BDBV vaccine through MVS production and IND-enabling toxicology testing, to establish the time to onset of protection provided by rVSVN4CT1-vectored vaccines against the four filovirus species of greatest concern (EBOV, SUDV, BDBV, and MARV). In addition, it proposes to address the questions regarding the vaccine valency providing the most effective formulation for use in a rapid response setting.",,2024,University Of Texas Med Br Galveston,963069,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21561,5R01AI148663-02,Intersection Between Viral Translation and Innate Immunity in the Context of Filovirus Infection,"The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) are negative-sense RNA viral pathogens that cause periodic outbreaks of severe disease in humans. Despite their importance as emerging pathogens and as public health threats, many aspects of filovirus biology remain understudied. One major knowledge gap concerns the function(s) of the non-protein coding sequences present in filovirus genomes that correspond to 5’ and 3’ untranslated regions (UTRs) in viral mRNAs. These sequences comprise ~22% of the MARV genome and a similar amount of the EBOV genome and yet have been barely studied. Another knowledge gap concerns mechanisms by which viral mRNAs are translated to protein and how this may be sustained when innate immune responses are activated. Beginning to address this, we previously demonstrated a role for an upstream open reading frame (uORF), present in the 5’UTR of the EBOV L open reading frame (ORF), in the regulation of L translation. We further implicated this uORF as providing a means to sustain L expression under conditions innate antiviral defenses are activated. These data support a role for the UTRs as translational regulators which can modulate viral gene expression in the face of innate antiviral defenses. Our recent profiling of MARV 3’UTR function suggests negative-regulatory elements are present in the nucleoprotein (NP) mRNA and that positive regulatory elements are present in the L mRNA. In addition, we previously reported that the MARV genome appears to be edited by adenosine deaminase activity, particularly in sequences corresponding to the nucleoprotein (NP) mRNA 3’UTR. We now show that such mutations substantially increase mRNA translation efficiency, suggesting a means to maintain NP expression when the IFN-induced p150 form of adenosine deaminase acting on RNA 1 (ADAR1) is upregulated. Interestingly, the regulatory elements within the wildtype NP 3’UTR are also capable of triggering innate immune responses, but this immune stimulating activity is alleviated by the presumptive ADAR1 editing mutations. To follow up on these observations, we propose a combination of transfection- and live virus-based experiments to define the translation regulatory elements in MARV and EBOV 3’ UTRs and to determine how ADAR1 editing impacts viral gene expression and virus replication. We will fully evaluate the capacity of MARV and EBOV 5’ and 3’UTRs to trigger innate antiviral responses, defining the sensors responsible for this induction. Finally, we will create recombinant MARVs with wildtype and mutant 3’UTR sequences. These will be tested in wildtype and ADAR1-deficient cells and mice in order to determine how translational regulatory elements and ADAR1 editing impact viral growth and pathogenesis. Cumulatively, these studies will provide significant new insight into filovirus-host interactions related to translation and innate immune evasion.",,2021,Georgia State University,194263,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21562,5R21AI146682-02,Intrinsically-enhanced Ebola and Marburg virus like particles for increased potency and immune memory,"Summary This developmental project seeks to develop methods to dramatically boost immunogenicity of virus-like particle (VLP) vaccines. Ebola virus (EBOV) and Marburg virus (MARV) are members of the filovirus family of enveloped, negative-sense RNA viruses that causes outbreaks of severe human disease. Due to their lethality, filoviruses are among the handful of emerging viruses for which biosafety level 4 (BSL4) containment is required for their study. Although progress has been made toward EBOV vaccines, there remains a need for development of vaccines for other filoviruses, particularly MARV. VLPs are an often-explored vaccine platform for a variety of viruses, including for EBOV and MARV. Advantages of VLPs include their relative safety, as they cannot replicate and cause viral disease; their close resemblance to authentic virus, such that they present antigens in their native state; their capacity to elicit both B and T cell responses and their proven efficacy for a variety of systems. Potential challenges of VLPs as vaccines include relatively lower immunogenicity, as compared to live virus. Filovirus VLPs can be produced by co-expression of the viral matrix protein VP40, the viral glycoprotein (GP), with or without expression of the viral nucleoprotein (NP). Such VLPs have been demonstrated to stimulate dendritic cell (DC) responses, to elicit B and T cell mediated immunity and to protect mice, guinea pigs and non- human primates (NHPs) from lethal challenge. Therefore, filovirus VLPs are viable vaccine candidates. However, filovirus VLP immunogenicity is weak with protection requiring coadministration with an adjuvant and multiple doses. This is not ideal for vaccines that are mainly deployed in response to outbreaks. This application seeks to dramatically improve immunogenicity of EBOV and MARV VLPs by the rational incorporation of type I interferon (IFN) signaling domains from the cellular pattern recognition receptors RIG-I or TRIF into the particles. This enables delivery into cells of the IFN inducing domain by the VLPs, triggering robust innate immune responses reminiscent of live virus infection, to boost adaptive immune responses. To further pursue this direction, we will explore approaches to optimize the incorporation of IFN-inducing signaling domains into EBOV and MARV VLPs. We will then evaluate the capacity of the different enhanced VLP strategies to elicit B and T cell immune responses in vivo, and finally, test the most promising enhanced VLPs for the capacity to elicit rapid protection against EBOV and MARV challenge in mice. Successful completion of these studies will provide a novel platform for the development of filovirus vaccines and an approach that can likely be applied to other emerging viral pathogens.",,2021,Georgia State University,31000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21563,7R01AI148663-03,Intersection Between Viral Translation and Innate Immunity in the Context of Filovirus Infection,"The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) are negative-sense RNA viral pathogens that cause periodic outbreaks of severe disease in humans. Despite their importance as emerging pathogens and as public health threats, many aspects of filovirus biology remain understudied. One major knowledge gap concerns the function(s) of the non-protein coding sequences present in filovirus genomes that correspond to 5’ and 3’ untranslated regions (UTRs) in viral mRNAs. These sequences comprise ~22% of the MARV genome and a similar amount of the EBOV genome and yet have been barely studied. Another knowledge gap concerns mechanisms by which viral mRNAs are translated to protein and how this may be sustained when innate immune responses are activated. Beginning to address this, we previously demonstrated a role for an upstream open reading frame (uORF), present in the 5’UTR of the EBOV L open reading frame (ORF), in the regulation of L translation. We further implicated this uORF as providing a means to sustain L expression under conditions innate antiviral defenses are activated. These data support a role for the UTRs as translational regulators which can modulate viral gene expression in the face of innate antiviral defenses. Our recent profiling of MARV 3’UTR function suggests negative-regulatory elements are present in the nucleoprotein (NP) mRNA and that positive regulatory elements are present in the L mRNA. In addition, we previously reported that the MARV genome appears to be edited by adenosine deaminase activity, particularly in sequences corresponding to the nucleoprotein (NP) mRNA 3’UTR. We now show that such mutations substantially increase mRNA translation efficiency, suggesting a means to maintain NP expression when the IFN-induced p150 form of adenosine deaminase acting on RNA 1 (ADAR1) is upregulated. Interestingly, the regulatory elements within the wildtype NP 3’UTR are also capable of triggering innate immune responses, but this immune stimulating activity is alleviated by the presumptive ADAR1 editing mutations. To follow up on these observations, we propose a combination of transfection- and live virus-based experiments to define the translation regulatory elements in MARV and EBOV 3’ UTRs and to determine how ADAR1 editing impacts viral gene expression and virus replication. We will fully evaluate the capacity of MARV and EBOV 5’ and 3’UTRs to trigger innate antiviral responses, defining the sensors responsible for this induction. Finally, we will create recombinant MARVs with wildtype and mutant 3’UTR sequences. These will be tested in wildtype and ADAR1-deficient cells and mice in order to determine how translational regulatory elements and ADAR1 editing impact viral growth and pathogenesis. Cumulatively, these studies will provide significant new insight into filovirus-host interactions related to translation and innate immune evasion.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,407579,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21564,1R21AI153815-01A1,Role of Host Angiomotin as a Central Regulator of Filovirus Egress and Dissemination,"Filoviruses (Ebola [EBOV] and Marburg [MARV]) and arenaviruses (e.g. Lassa virus; LAFV) are zoonotic, emerging pathogens that cause outbreaks of severe hemorrhagic fever in humans and non-human primates. A fundamental understanding of the virus-host interface is critical for developing future strategies and countermeasures for therapeutic intervention. As the filovirus VP40 and LAFV Z matrix proteins drive virion assembly and egress, in part, by hijacking specific host proteins containing WW-domains that can interact with their highly conserved PPxY L-domain motifs, these interactions represent a novel therapeutic target to inhibit egress and dissemination of these hemorrhagic fever viruses. Our early studies to identify host WW-domain proteins that regulate filovirus and arenavirus budding identified the E3 ubiquitin ligases Nedd4, ITCH, and WWP1 as positive regulators of viral PPxY-mediated budding. However, in more recent studies, we identified WW-domain containing proteins YAP/TAZ, BAG3, and now WWOX (WW Domain Containing Oxidoreductase; a multi-functional tumor suppressor), as negative regulators of PPxY-mediated egress of VP40 and Z VLPs. The identification of YAP/TAZ, BAG3, and WWOX as negative regulators of viral PPxY-mediated budding is particularly intriguing since all three of these proteins interact with Angiomotin (Amot), a multi-PPxY containing protein that functions as a “master regulator” of Hippo pathway (YAP/TAZ) signaling, cytoskeletal dynamics, cell migration/proliferation, and tight junction (TJ) integrity. Moreover, expression and stability of Amot itself are regulated by PPxY/WW-domain interactions with the Nedd4 family of E3 ubiquitin ligases. Thus, we hypothesize that Amot is a central interactor linking both the positive and negative WW-domain containing regulators of virus egress, and that modular mimicry between viral and host PPxY motifs and the competitive nature of their binding to the same host WW-domain containing proteins will have a major impact on both cellular processes and viral replication and pathogenesis. Indeed, we were first to report that expression of endogenous Amot positively regulates PPxY-mediated egress of EBOV and MARV VP40 VLPs as well as egress and spread of live EBOV and MARV in cell culture. In this proposal, we will build upon our novel finding that PPxY-containing Amot can positively regulate egress and spread of PPxY-containing viruses including EBOV and MARV, and determine whether the competitive PPxY/WW-domain interplay among VP40/Z â€Â"" Amot â€Â"" host WW-domain interactors regulates egress of VLPs and live viruses in vitro and in vivo. Successful completion of these aims will provide novel insights into how this complex network of modular PPxY/WW-domain interactions with Amot impacts late stages of hemorrhagic fever virus egress and dissemination and serve as proof-of principle for therapeutic strategies targeting an essential viral-host interaction that may represent an Achilles heel for numerous RNA viruses.",,2023,University Of Pennsylvania,285833,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21565,5R21AI142651-02,Investigation of the role of phosphatidic acid metabolism in filovirus budding,"Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Filoviruses are lipid-enveloped viruses that have a filamentous lipid-envelope and despite being discovered more than 40 years ago, not much is known on how they acquire their lipid coat. These viruses bud from the plasma membrane of the host cell and cause viral hemorrhagic fever with up to a 90% fatality rate. Filoviruses include Ebola virus (EBOV) and Marburg virus (MARV), which are classified as category A pathogens by the NIH as they pose a serious public health and national security risk. These viruses harbor a negative sense RNA genome that encodes seven genes. The viral matrix protein VP40, which regulates budding from the host cell membrane, underlies the viral lipid envelope. VP40 is a peripheral protein and the only protein required from these viruses to form filamentous virus like particles that are nearly indistinguishable from authentic virions. Since little is known about how VP40 interacts with biological membranes, many fundamental questions about Filovirus assembly and budding remain unanswered. Preliminary studies demonstrate that a host cell enzyme, phospholipase D, is required for sufficient viral particle release and VP40 particle displacement at the plasma membrane. Phospholipase D is an enzyme that uses phosphatidylcholine as a substrate to generate the anionic lipid phosphatidic acid (PA). Preliminary studies also demonstrate that VP40 protein expression in human cells is sufficient to increase cellular levels of PA. The central hypothesis of this proposal is that the host enzyme phospholipase D (PLD) plays an essential role in the late stage budding of filoviruses. This R21 application describes experiments to provide a cohesive cellular and biochemical model of the role of PLD activity and PA generation in Filovirus budding. Specific Aim 1 will investigate the role of PLD activity and PA generation in the cellular assembly and budding of EBOV and MARV. We will elucidate the potential for inhibition of synthesis of this glycerophospholipid to inhibit Filovirus budding. Experiments with a BSL-4 collaborator will also test this hypothesis against authentic EBOV and MARV. Specific aim 2 will investigate the mechanism by which PA stabilizes VP40 oligomers and the molecular origin of PA binding by VP40. Quantitative measurements in our live cell BSL-2 surrogate system will determine the kinetics of VLP assembly and release and the role of PLD activity and PA generation in stabilizing VP40 oligomers at the plasma membrane for the scission process. The molecular origins of PA binding will be investigated using strong rationale of lipid-protein interactions and the known VP40 structures. Taken together, these studies should produce new and important mechanistic insight into how Filovirus particles form from the plasma membrane of cells.",,2023,Purdue University,251250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21566,1R01AI158220-01A1,Computational and Biophysical Analysis of the Filovirus Matrix Protein System,"Project Summary Ebola (EBOV) and Marburg (MARV) filoviruses cause severe hemorrhagic fever in humans with up to 90% mortality rates. Their genome contains only seven genes including the viral matrix protein VP40 which, when expressed in mammalian cells, is sufficient to produce virus-like particles (VLPs) that are essentially indistinguishable from live virions. VP40 forms dimers, hexamers and octamers mediated by different protein-protein (PPI) and protein-lipid (PLI) interactions that fulfill different and essential roles in the viral lifecycle, making VP40 a “swiss army knife” of proteins. The fascinating dynamic equilibria of VP40 and the availability of VLPs as a model system for direct observations outside of a BSL4 laboratory make VP40 a unique system to rigorously study the biophysical basis for viral budding as well as PPIs and PLIs in general. The significance of these studies is further increased because VP40 is the most conserved protein upon virus passage through humans, but exploiting VP40 as a potential drug target is unlikely to succeed without understanding the physical basis for oligomerization and function of VP40. The Stahelin and Wiest laboratories, building on established collaborations with each other and several other collaborators supplying specific expertise, will use computational, experimental and structural biophysics methods to investigate the central hypothesis of this grant: that interdomain interactions of VP40 are key regulators of VP40 structures during the viral life cycle. In two specific aims, we will (i) Determine the biophysical mechanisms by which VP40 dimer, hexamer and octamers form in silico, in vitro and in human cells and (ii) determine how mutations of VP40 that arise in humans during the course of an outbreak as well as in animals during passage of virus contribute to VP40 conformational change and rearrangement into its separate oligomeric forms. These questions will be studied using a tightly integrated approach using multiscale molecular dynamics simulations on the Ã'µs timescale and free energy perturbation methods on the computational side and hydrogen-deuterium exchange, cellular imaging of VLPs as well as more traditional biophysical experiments such as ultracentrifugation and SPR to determine the binding constants of wildtype VP40 from EBOV and MARV as well as pertinent mutants. This innovate and integrated approach will not only provide careful validation of the results, but also provide detailed insights into the PPIs and PLIs governing the oligomerization equilibria across many time- and lengths scale, thus enabling a rigorous understanding of the biophysical principles for a biomedically very important filovirus protein that will have a significant impact on understanding other PPIs and PLIs.",,2026,Purdue University,727573,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P21567,1R21AI151483-01A1,Structure-Based Design of Peptide Entry Inhibitors against Ebola Virus Infection,"Abstract Ebola viruses (EBOV) along with Marburg viruses (MARV) belong to the Filoviridae family which infects humans and nonhuman primates and causes outbreaks with a high mortality up to 90%. We do not have approved drugs for treating this deadly viral disease and therefore it is urgent to develop therapeutics to cope with the dangerous outbreaks. In this project, we propose to develop peptide based inhibitors targeting the receptor binding site (RBS) to block viral infection. We will conduct structure based design using the available co-crystal structures of the NPC1 receptor or monoclonal antibodies bound to the viral glycoprotein. The initial evaluation will utilize pseudo- typed viruses to test viral entry in a cell based assay. The best peptide candidates from these assays will subsequently be tested in a BSL-4 containment facility using replication competent viruses for entry inhibition tests. In vivo evaluations of qualified candidates will be conducted in a virus challenge mouse model to measure protection efficacy. After all these evaluations, promising candidates could be advanced to nonhuman primates or human clinical trials.",,2022,University Of Nebraska Lincoln,259074,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21568,1R21AI151732-01,Host factors and inhibition of Filoviruses,"Ebola virus (EBOV) and Marburg virus (MARV) are highly lethal hemorrhagic fever viruses of the Filoviridae family of viruses. Currently, there are no effective oral or easily scalable therapies for either virus. Both EBOV and MARV manifest vigorous anti-host evasion strategies focused on blocking the host antiviral interferon response. Both viruses interfere with host cell sensing of infection via their structural protein VP35, which inhibits viral dsRNA sensing and triggering of the host antiviral response. Therapeutic strategies that enhance host pathways that are inhibited by these viruses could therefore be of significant value. We have discovered that the well-tolerated FDA-approved oral anti-parasitic drug nitazoxanide (NTZ) inhibits infectious EBOV replication in human A549 cells in vitro. Furthermore, we find that NTZ enhances the RIG-I-like receptor (RLR) proteins retinoic-acid-inducible protein I (RIG- I) and Melanoma Differentiation-Associated protein 5 (MDA5), their common adaptor protein mitochondrial antiviral signaling protein (MAVS), the IFN-inducible double-stranded (ds) RNA sensor protein kinase R (PKR), and interferon signaling pathways. In addition, using deadCas9/CRISPR editing, we ablated RIG-I and PKR in A549 cells, and found that EBOV growth was significantly increased and in parallel NTZ's inhibitory effects were significantly attenuated. These results thus indicate that RIG-I and PKR are both required and non-redundant host restriction factors for EBOV. Moreover, PKR and RIG-I are both targeted by and necessary for NTZ's action indicating that NTZ counteracts the EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV infection. In Aim 1 of this proposal, we will test the hypothesis that NTZ also inhibits MARV in vitro, which we strongly expect given the importance of MARV's VP-35 protein in its pathogenesis. In Aim 1, we will also test our hypothesis that NTZ inhibits both EBOV and MARV in vivo in the guinea pig model. In Aim 2, we will test the impact of MDA5 or MAVS inhibition, in addition to studying RIG-I, PKR or GADD34 depletion on MARV replication. We will compare these results to experiments evaluating EBOV replication in monocytic THP-1 cells. These experiments will evaluate the role of these discrete sensors in NTZ's inhibitory effects upon EBOV and MARV and it will test the hypothesis that NTZ works through PKR and RIG-I in inhibition of MARV as it does in EBOV infection. Building on these studies, using an unbiased RNA-seq approach, we will determine transcriptomic signatures of cellular perturbations induced by NTZ in the setting of EBOV and MARV infection allowing us to define host immune regulatory circuits involved in cytoplasmic sensing of EBOV and MARV and the impact of NTZ. We anticipate that these studies will provide scientific underpinning for repurposing NTZ as a therapy for EBOV and MARV and uncover key innate immune molecules that control their pathogenesis.",,2022,BOSTON CHILDREN'S HOSPITAL,270500,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +P21569,1R01AI148663-01A1,Intersection Between Viral Translation and Innate Immunity in the Context of Filovirus Infection,"The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) are negative-sense RNA viral pathogens that cause periodic outbreaks of severe disease in humans. Despite their importance as emerging pathogens and as public health threats, many aspects of filovirus biology remain understudied. One major knowledge gap concerns the function(s) of the non-protein coding sequences present in filovirus genomes that correspond to 5’ and 3’ untranslated regions (UTRs) in viral mRNAs. These sequences comprise ~22% of the MARV genome and a similar amount of the EBOV genome and yet have been barely studied. Another knowledge gap concerns mechanisms by which viral mRNAs are translated to protein and how this may be sustained when innate immune responses are activated. Beginning to address this, we previously demonstrated a role for an upstream open reading frame (uORF), present in the 5’UTR of the EBOV L open reading frame (ORF), in the regulation of L translation. We further implicated this uORF as providing a means to sustain L expression under conditions innate antiviral defenses are activated. These data support a role for the UTRs as translational regulators which can modulate viral gene expression in the face of innate antiviral defenses. Our recent profiling of MARV 3’UTR function suggests negative-regulatory elements are present in the nucleoprotein (NP) mRNA and that positive regulatory elements are present in the L mRNA. In addition, we previously reported that the MARV genome appears to be edited by adenosine deaminase activity, particularly in sequences corresponding to the nucleoprotein (NP) mRNA 3’UTR. We now show that such mutations substantially increase mRNA translation efficiency, suggesting a means to maintain NP expression when the IFN-induced p150 form of adenosine deaminase acting on RNA 1 (ADAR1) is upregulated. Interestingly, the regulatory elements within the wildtype NP 3’UTR are also capable of triggering innate immune responses, but this immune stimulating activity is alleviated by the presumptive ADAR1 editing mutations. To follow up on these observations, we propose a combination of transfection- and live virus-based experiments to define the translation regulatory elements in MARV and EBOV 3’ UTRs and to determine how ADAR1 editing impacts viral gene expression and virus replication. We will fully evaluate the capacity of MARV and EBOV 5’ and 3’UTRs to trigger innate antiviral responses, defining the sensors responsible for this induction. Finally, we will create recombinant MARVs with wildtype and mutant 3’UTR sequences. These will be tested in wildtype and ADAR1-deficient cells and mice in order to determine how translational regulatory elements and ADAR1 editing impact viral growth and pathogenesis. Cumulatively, these studies will provide significant new insight into filovirus-host interactions related to translation and innate immune evasion.",,2025,Georgia State University,550373,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P21570,1R21AI146682-01A1,Intrinsically-enhanced Ebola and Marburg virus like particles for increased potency and immune memory,"Summary This developmental project seeks to develop methods to dramatically boost immunogenicity of virus-like particle (VLP) vaccines. Ebola virus (EBOV) and Marburg virus (MARV) are members of the filovirus family of enveloped, negative-sense RNA viruses that causes outbreaks of severe human disease. Due to their lethality, filoviruses are among the handful of emerging viruses for which biosafety level 4 (BSL4) containment is required for their study. Although progress has been made toward EBOV vaccines, there remains a need for development of vaccines for other filoviruses, particularly MARV. VLPs are an often-explored vaccine platform for a variety of viruses, including for EBOV and MARV. Advantages of VLPs include their relative safety, as they cannot replicate and cause viral disease; their close resemblance to authentic virus, such that they present antigens in their native state; their capacity to elicit both B and T cell responses and their proven efficacy for a variety of systems. Potential challenges of VLPs as vaccines include relatively lower immunogenicity, as compared to live virus. Filovirus VLPs can be produced by co-expression of the viral matrix protein VP40, the viral glycoprotein (GP), with or without expression of the viral nucleoprotein (NP). Such VLPs have been demonstrated to stimulate dendritic cell (DC) responses, to elicit B and T cell mediated immunity and to protect mice, guinea pigs and non- human primates (NHPs) from lethal challenge. Therefore, filovirus VLPs are viable vaccine candidates. However, filovirus VLP immunogenicity is weak with protection requiring coadministration with an adjuvant and multiple doses. This is not ideal for vaccines that are mainly deployed in response to outbreaks. This application seeks to dramatically improve immunogenicity of EBOV and MARV VLPs by the rational incorporation of type I interferon (IFN) signaling domains from the cellular pattern recognition receptors RIG-I or TRIF into the particles. This enables delivery into cells of the IFN inducing domain by the VLPs, triggering robust innate immune responses reminiscent of live virus infection, to boost adaptive immune responses. To further pursue this direction, we will explore approaches to optimize the incorporation of IFN-inducing signaling domains into EBOV and MARV VLPs. We will then evaluate the capacity of the different enhanced VLP strategies to elicit B and T cell immune responses in vivo, and finally, test the most promising enhanced VLPs for the capacity to elicit rapid protection against EBOV and MARV challenge in mice. Successful completion of these studies will provide a novel platform for the development of filovirus vaccines and an approach that can likely be applied to other emerging viral pathogens.",,2022,Georgia State University,209214,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21572,1R21AI142651-01A1,Investigation of the role of phosphatidic acid metabolism in filovirus budding,"Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Filoviruses are lipid-enveloped viruses that have a filamentous lipid-envelope and despite being discovered more than 40 years ago, not much is known on how they acquire their lipid coat. These viruses bud from the plasma membrane of the host cell and cause viral hemorrhagic fever with up to a 90% fatality rate. Filoviruses include Ebola virus (EBOV) and Marburg virus (MARV), which are classified as category A pathogens by the NIH as they pose a serious public health and national security risk. These viruses harbor a negative sense RNA genome that encodes seven genes. The viral matrix protein VP40, which regulates budding from the host cell membrane, underlies the viral lipid envelope. VP40 is a peripheral protein and the only protein required from these viruses to form filamentous virus like particles that are nearly indistinguishable from authentic virions. Since little is known about how VP40 interacts with biological membranes, many fundamental questions about Filovirus assembly and budding remain unanswered. Preliminary studies demonstrate that a host cell enzyme, phospholipase D, is required for sufficient viral particle release and VP40 particle displacement at the plasma membrane. Phospholipase D is an enzyme that uses phosphatidylcholine as a substrate to generate the anionic lipid phosphatidic acid (PA). Preliminary studies also demonstrate that VP40 protein expression in human cells is sufficient to increase cellular levels of PA. The central hypothesis of this proposal is that the host enzyme phospholipase D (PLD) plays an essential role in the late stage budding of filoviruses. This R21 application describes experiments to provide a cohesive cellular and biochemical model of the role of PLD activity and PA generation in Filovirus budding. Specific Aim 1 will investigate the role of PLD activity and PA generation in the cellular assembly and budding of EBOV and MARV. We will elucidate the potential for inhibition of synthesis of this glycerophospholipid to inhibit Filovirus budding. Experiments with a BSL-4 collaborator will also test this hypothesis against authentic EBOV and MARV. Specific aim 2 will investigate the mechanism by which PA stabilizes VP40 oligomers and the molecular origin of PA binding by VP40. Quantitative measurements in our live cell BSL-2 surrogate system will determine the kinetics of VLP assembly and release and the role of PLD activity and PA generation in stabilizing VP40 oligomers at the plasma membrane for the scission process. The molecular origins of PA binding will be investigated using strong rationale of lipid-protein interactions and the known VP40 structures. Taken together, these studies should produce new and important mechanistic insight into how Filovirus particles form from the plasma membrane of cells.",,2022,Purdue University,205700,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21573,1R01AI182049-01,"The B22 family of orthopoxvirus virulence factors: Investigating structure/function of these potent, multifaceted immunoevasins","Several members of the orthopoxvirus (OPXV) genus, including variola (the cause of smallpox), monkeypox virus (MPXV) and camelpox virus (CMPV) pose serious threats to human health, while the ultimate impact of emerging OPXVs of concern such as Alaskapox virus (AKPV) is unknown. Other OPXVs are highly pathogenic in their natural hosts, including ectromelia (ECTV), the cause of mousepox - a disease with many similarities to smallpox. It is concerning, then, that the extreme virulence typical of the OPXVs remains poorly understood. Central to OPXV virulence are the virus-encoded proteins that impede host defenses. This proposal focuses on members of the B22 family of OPXV immunoevasins due to their potency, complexity and limited characterization. With respect to potency, MPXV197 significantly enhances mortality in a nonhuman primate model, and ECTV C15 alone determines whether ECTV is 100% lethal or 100% survivable in a BALB/c mouse infection model. With respect to complexity, B22 family members are exceedingly large (~1900 aa), highly homologous multimembrane-spanning glycoproteins. We have observed that C15 is novel in targeting both adaptive and innate host responses, preventing activation of CD4+ and CD8+ T cells (TCD4 and TCD8), and interfering with the ability of natural killer (NK) cells to engage infected cells. Other B22 members have been implicated in hindering only TCD4 and/or TCD8 function; however, given the high degrees of homology, we suspect common functionalities, including targeting of NK cells. With respect to limited characterization, essentially no structure/function studies have been done with any B22 member. Through application of such studies to B22 members, key insights into OPXV virulence will be gained, potentially leading to novel therapeutic strategies and enhanced general principles of viral virulence. Guided by published and preliminary data, we propose a model in which topologically complex B22 members contain two functional subunits created by posttranslational cleavage: 1) an upstream (N-terminal) subunit that interferes with NK cell recognition via an MHC class I-like structure. 2) a C-terminal subunit that inhibits conjugation of TCD4 and TCD8 with their cognate targets. This model will be tested by pursuing three complementary aims that: 1) reveal the structural properties of B22 members, 2) identify and map the functional activities of B22 members, and 3) elucidate the viral and cellular binding partners of B22 proteins. The value of these studies derives from: a) the significance of many OPXV members as human pathogens, b) the potency of B22 members as virulence factors, c) the enigmatic immunoevasion activities of B22 members, and d) the potential for the proposed work to lead to new insights into virus:host interplay, the development of novel antiviral strategies and many future lines of investigation, including elucidation of the advantage to aggregating innate and adaptive immunoevasion activities into a single protein.",,2028,CHILDREN'S HOSP OF PHILADELPHIA,668007,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2024 +P21574,5R21AI174037-02,Comprehensive genetic dissection of poxvirus membrane assembly and function,"The zoonotic potential of members of the genus Orthopoxvirus (orthopoxviruses) of mammal- infecting poxviruses represent a continued threat to global public health. A hallmark of the complex biology of orthopoxvirus multiplication in the host cell cytoplasm is the generation of two distinct infectious formsâ€Â""intracellular mature virions (IMV), which remain largely cell- associated, and enveloped virions (EV), which are critical for extracellular viral spread. EVs bear a unique complement of eight virus-encoded membrane proteins at their surface that influence tissue tropism, long-range in vivo dissemination, and ultimately, virulence; provide key targets for vaccine-induced and therapeutic antibodies; and are important determinants of the therapeutic potential of oncolytic poxvirus vectors. Despite their importance, a comprehensive understanding of EVs is challenged by the complex networks of virus-host and virus-virus interactions that underlie their morphogenesis and function. Our overall objective is to unravel these functional protein interaction networks through a combination of genetic and proteomic approaches. Using a new platform for unbiased and deep mutagenesis of any genomic locus in the prototypic orthopoxvirus, vaccinia virus (VACV), we conducted deep-mutational scans (DMS) of two EV proteins, A33 and A34, in the context of infectious viral particles and identified novel regiospecific mutations that enhance EV fitness. We will elucidate the mechanisms of action of these mutants. In parallel, we will perform genetic modifier and proteomic screens to uncover new functional interactions of A33/A34 with viral and host proteins. Collectively, these studies will provide new information on how EVsâ€Â""critical for both the virulence of orthopoxviruses and their utility as oncolytic vectorsâ€Â""assemble, egress, and spread to new cells during infection.",,2024,ALBERT EINSTEIN COLLEGE OF MEDICINE,189000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease | Viral evolution in different contexts & implications,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P21575,1R21AI178638-01,Poxvirus-encoded noncanonical open reading frames,"Poxviruses are a large family of viruses including species that are highly pathogenic for humans and animals, including smallpox and monkeypox viruses. Some poxviruses are developed as vaccine vectors and oncolytic virotherapies to fight other infectious diseases and cancers. Vaccinia virus, the prototype poxvirus, has previously been annotated to encode over 200 open reading frames in its 200kbp genome. Our genome-wide analysis of vaccinia virus gene expression using RNA-sequencing uncovered that numerous unexpected mRNAs are transcribed. Furthermore, our previous study discovered a large number of (>500) novel translation initiation sites associated with previously unrecognized non-canonical open reading frames (ORFs) using ribosome profiling. Much remains unknown about the biological relevance of these non-canonical ORFs. The objective of this proposal is to characterize the peptides encoded by the non-canonical vaccinia virus ORFs and explore the biological relevance and functions. The central hypothesis is that peptides/proteins are produced from the non-canonical ORFs, which may play important roles in VACV replication. In Specific Aim 1, peptides/proteins encoded by vaccinia virus non-canonical ORFs will be identified. In Specific Aim 2, the roles of representative non-canonical ORFs in vaccinia virus replication will be determined. Completion of the project is expected to provide knowledge of the expression and functions of the non-canonical poxvirus ORFs that are previously unrecognized. It has profound implications in interpreting poxvirus genetic studies since the past studies have been focusing on previously annotated large ORFs. The outcomes may transform the understanding of poxvirus gene expression and break ground toward new directions in the field. Better understanding these newly identified ORFs may ultimately lead to novel intervening strategies and improving poxviruses as vaccine vectors and cancer therapeutics agents. Therefore, the outcomes are also expected to have a broad impact beyond the poxviruses, as the genomes of various organisms, including humans, also encoded many previously unrecognized ORFs.",,2025,TEXAS A&M AGRILIFE RESEARCH,183220,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease | Viral evolution in different contexts & implications,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P21576,5U01CK000666-02,"RFA-CK-22-001, Investigation of Monkeypox and Other Zoonotic Diseases in the Democratic Republic of the Congo (DRC) - 2022","The goals of this project are to improve the scientific understanding and reduce the clinical burden of Monkeypox (MPX) and other zoonotic diseases in Democratic Republic of the Congo (DRC). This should directly support the U.S. CDC mission of strengthening public health surveillance systems globally to prevent the spread of emerging diseases. This project will rely upon the Kinshasa School of Public Health’s considerable experience with training public health practitioners, conducting scientific research trials, and supporting the DRC Ministry of Health to accomplish its objectives. The project will be framed around a laboratory-based surveillance system for MPX in DRC to collect accurate case burden data. We will expand upon this framework by evaluating new training methods for health workers, improving geographic data, and assessing new diagnostic platforms when available. We will use our relationships with health systems in highly affected areas to conduct clinical trials of care regimens, vaccines, and anti-viral therapies. We will perform serosurveys in high-risk and survivor populations to better understand transmission risk factors, viral persistence, and sequalae. We will work with key groups in these areas to identify wildlife reservoirs of MPX and collect qualitative data on the attitudes and behaviors of key populations living in these communities. We will work with the government of DRC to improve the ability to respond to outbreaks quickly by preemptively training response workers, developing health promotion networks, and responding to misinformation rapidly. We will share results with national stakeholders and other nations interested in being better prepared for responding to endemic and imported MPX cases.",,2027,KINSHASA SCHOOL OF PUBLIC HEALTH,700000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Africa,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Investigation of zoonotic transmission & reservoirs | Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Ongoing assessment & evaluation of surveillance,Congo (DRC),,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Therapeutics research, development and implementation | Vaccines research, development and implementation | Research on Capacity Strengthening",Diagnostics | Animal source and routes of transmission | Disease surveillance & mapping | Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase) | Individual level capacity strengthening,2022 +P21577,1R01AI175567-01A1,Mechanisms of protective memory CD8 T-cell induction by mRNA-LNP vaccines,"CD8 T-cells recognize and kill virus-infected cells displaying at the cell surface short viral peptides bound to major histocompatibility (MHC) class I molecules (MHC-I). CD8 T-cells contribute to the clearance of many viral infections. After an infection subsides, an expanded population of “memory” CD8 T-cells (M CD8 T-cells) may contribute to more rapidly controlling a secondary infection with the virus. Vaccines can mimic this process. Modified mRNA (mmRNA) encapsulated in lipid nanoparticles (mmRNA-LNP) have emerged as a powerful vaccine platform. mmRNA-LNPs have many advantages as vaccines: 1) They can be focused on the antigen of interest. 2) They are highly immunogenic. 3) they are easy to make. 4) They can be mass-produced rapidly. 5) They are relatively inexpensive. The swift development and approval of the mmRNA-LNP vaccines to combat SARS-CoV-2 attest to their potential. While it is known that mmRNA-LNPs induce CD8 T-cell responses, most of the work on their protection mechanisms has focused on Abs. The mCD8 T-cells induced by mmRNA- LNP can potentially complement Ab protection or may provide most of the protection for viruses that are refractory to Ab-mediated control. mmRNA-LNPs could also be used to induce CD8 T-cells against cancer. We have published that the mCD8 T-cell responses induced by mmRNA-LNPs protect mice from highly lethal mousepox, a systemic viral disease of the mouse caused by the Orthopoxvirus (OPV) ectromelia virus (ECTV). ECTV is an outstanding model for systemic viral infections in general and for OPVs that can infect humans, such as the eradicated variola virus (virus of smallpox) and for monkeypox virus (MPXV), which recently caused a major outbreak. In still unpublished experiments, we also found that M CD8 T-cells induced by a mini- mmRNA vaccine encoding for only the minimal, highly conserved CD8 T-cell epitope VNFNFNGL of the SARS- CoV-2 Spike protein protects wild-type mice from lethal respiratory infection with the mouse-adapted SARS- CoV-2 strain MA30, an outstanding model for SARS-CoV-2 and other grave respiratory infections. Here we propose elucidating the mechanisms whereby mmRNA-LNPs induce protective mCD8 T-cells using the ECTV systemic and the MA30 SARS-CoV-2 respiratory mouse models. Our Specific Aims are to: A) Specific Aim 1. Investigate the Mechanisms of MHC-I antigen presentation after mmRNA-LNP vaccination. B) Specific Aim 2. Investigate the roles of Type I interferon (IFN-I) and other proinflammatory cytokines in protective M CD8 T-cell development after mRNA-LNP vaccination.",,2028,Thomas Jefferson University,722737,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Poxviridae,,,,,,,,,COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21578,272201800013I-P00001-759302200004-1,TASK V15: DEVELOPMENT OF ASSAYS AND REAGENTS FOR VACCINES,The Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases contract provides a variety of product development services from early feasibility studies through activities required for the submission of Biologic License Application (BLA) and/or Investigational New Drug (IND) applications. These services will facilitate the development and introduction of new vaccine candidates and biologics (regulated by CBER) against potential agents of bioterrorism and emerging and re-emerging infectious diseases.,,2024,BATTELLE CENTERS/PUB HLTH RES & EVALUATN,484304,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",,2022 +P21579,1R21AI174037-01,Comprehensive genetic dissection of poxvirus membrane assembly and function,"The zoonotic potential of members of the genus Orthopoxvirus (orthopoxviruses) of mammal- infecting poxviruses represent a continued threat to global public health. A hallmark of the complex biology of orthopoxvirus multiplication in the host cell cytoplasm is the generation of two distinct infectious formsâ€Â""intracellular mature virions (IMV), which remain largely cell- associated, and enveloped virions (EV), which are critical for extracellular viral spread. EVs bear a unique complement of eight virus-encoded membrane proteins at their surface that influence tissue tropism, long-range in vivo dissemination, and ultimately, virulence; provide key targets for vaccine-induced and therapeutic antibodies; and are important determinants of the therapeutic potential of oncolytic poxvirus vectors. Despite their importance, a comprehensive understanding of EVs is challenged by the complex networks of virus-host and virus-virus interactions that underlie their morphogenesis and function. Our overall objective is to unravel these functional protein interaction networks through a combination of genetic and proteomic approaches. Using a new platform for unbiased and deep mutagenesis of any genomic locus in the prototypic orthopoxvirus, vaccinia virus (VACV), we conducted deep-mutational scans (DMS) of two EV proteins, A33 and A34, in the context of infectious viral particles and identified novel regiospecific mutations that enhance EV fitness. We will elucidate the mechanisms of action of these mutants. In parallel, we will perform genetic modifier and proteomic screens to uncover new functional interactions of A33/A34 with viral and host proteins. Collectively, these studies will provide new information on how EVsâ€Â""critical for both the virulence of orthopoxviruses and their utility as oncolytic vectorsâ€Â""assemble, egress, and spread to new cells during infection.",,2024,ALBERT EINSTEIN COLLEGE OF MEDICINE,252000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease | Viral evolution in different contexts & implications,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P21580,1R43AI179443-01,Discovery of antiviral inhibitors for the treatment of orthopoxvirus infections,"PROJECT SUMMARY Smallpox (caused by variola virus infection) was one of the most destructive diseases in human history, resulting in 300-500 million deaths in the twentieth century alone until it was finally eradicated in 1980. Following elimination of variola virus, global vaccination programs were eventually halted and as a result, most of the world’s population is no longer immunologically protected from smallpox nor does it enjoy cross- protection to other orthopoxviruses. There are two drugs approved for smallpox disease, however, both compounds possess significant limitations. A lack of therapeutic options for treating orthopoxvirus infections continues to expose the population to grave risk from a smallpox bioweapon as well as future zoonotic orthopoxvirus infections. During the course of the Phase I funding period, we will execute a hit finding campaign against a library of >200,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven hit-to-lead to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or more novel lead series which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against variola virus and other orthopoxviruses with minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection.",,2025,"VENATORX PHARMACEUTICALS, INC.",300000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21581,75N91019D00024-0-759102200024-1,MONKEYPOX VACCINE CLINICAL TRIAL ,To support a Phase II clinical trial evaluating alternative strategies for administering the JYNNEOS monkeypox vaccine to increase the number of available doses.,,2024,"LEIDOS BIOMEDICAL RESEARCH, INC.",11497606,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Vaccines research, development and implementation",Immunisation strategies to optimise use of available vaccines,United States of America,,"Vaccines research, development and implementation",Phase 2 clinical trial,2022 +P21582,275201800001I-0-759402200004-1,A5418 STUDY OF TECOVIRIMAT FOR HUMAN MONKEYPOX VIRUS (STOMP),"ACTG A5418: A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease, Study of Tecovirimat for Human Monkeypox Virus (STOMP) CLINICAL COORDINATION, MONITORING AND EVALUATION OF THE AIDS CLINICAL TRIALS GROUP PROTOCOL A5418 STUDY OF TECOVIRIMAT FOR HUMAN MONKEYPOX VIRUS (STOMP). A5418 (STOMP) is a study of tecovirimat (also known as TPOCC) for the treatment of human monkeypox virus (HMPXV) disease. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring a Phase 3 clinical trial evaluating the antiviral tecovirimat, also known as TPOXX, for the treatment of human monkeypox infection. The NIAID-funded AIDS Clinical Trials Group (ACTG) is leading the study, which is now enrolling adults and children with monkeypox infection in the United States. Study investigators aim to enroll more than 500 people from up to 80 clinical research sites nationwide. Adults with severe monkeypox, severe immunodeficiency, or severe inflammatory skin conditions; individuals taking certain medications that could affect tecovirimat levels; and pregnant people, people who are breastfeeding and children all will be enrolled in an open-label arm in which all participants receive tecovirimat. Other adult participantsâ€Â""530 totalâ€Â""will be randomly assigned in a 2:1 ratio to receive tecovirimat or placebo pills, which participants will take for 14 days. This part of the trial is double-blind, meaning neither participants nor investigators will know who is receiving placebo or tecovirimat. Investigators will gather data to determine if participants receiving tecovirimat heal more quickly and have less pain compared with those taking placebo. Participants will be followed for at least 57 days and will be asked to fill out a symptom diary, do daily skin checks at home and attend virtual and in-person clinic appointments. They also will undergo physical exams and will be asked to provide blood and other bodily fluid samples, including swabbing fluid from their lesions. Data on the safety and efficacy of tecovirimat will be submitted to the FDA. An independent Data and Safety Monitoring Board (DSMB) will monitor participant safety throughout the duration of the study. In addition, any participant in the randomized cohort who progresses to severe disease will be unblinded and given tecovirimat if they were randomized to placebo.",,2024,"WESTAT, INC.",605168,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women,Unspecified,Clinical,"Clinical Trial, Phase III",Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Phase 3 clinical trial,2022 +P21583,75N93019C00045-P00012-9999-2,Characterize and optimize adjuvants to test monkeypox vaccines,"To identify novel classes of adjuvants, characterize and optimize them, and test them in vivo with various antigens from different pathogens.",,2022,University Of Montana,1599006,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21584,75N93021C00012-P00005-9999-6,Statistical Data Coordinating Center: Monkeypox Clinical Research Support,"The goal of the Statistical and Data Coordinating Center is to provide comprehensive statistical support, data management and analysis activities for DMID-sponsored clinical research trials. This includes internet-based electronic data collection, data management, data quality control and a specimen tracking system. In addition, the contractor provides consultation on statistics, study design, appropriate control groups, sample size, power calculations, randomization, stratification, and analysis.",,2022,"THE EMMES COMPANY, LLC",435519,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2021 +P21585,272201800013I-0-759302200004-1,TASK V17: DEVELOPMENT OF ASSAYS AND REAGENTS FOR MONKEYPOX VACCINES,The Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases contract provides a variety of product development services from early feasibility studies through activities required for the submission of Biologic License Application (BLA) and/or Investigational New Drug (IND) applications. These services will facilitate the development and introduction of new vaccine candidates and biologics (regulated by CBER) against potential agents of bioterrorism and emerging and re-emerging infectious diseases.,,2023,BATTELLE CENTERS/PUB HLTH RES & EVALUATN,1045131,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P21586,3UM1AI106701-09S1,Study of Tecovirimat for Human Monkeypox Virus (STOMP),"PROJECT SUMMARY The AIDS Clinical Trials Group (ACTG) has been at the forefront of clinical research to advance HIV therapeutics and improve the health of patients living with HIV/AIDS for 25 years. Rigorous scientific research conducted by the ACTG has laid the cornerstones for current HIV treatment guidelines. In this application for the competitive renewal of the ACTG Network Laboratory Center, we propose a transformative laboratory research agenda that draws on an international consortium of prominent clinical and laboratory investigators in collaboration with a world-class Statistical and Data Management Center to conduct leading edge laboratory research, testing, assay development and laboratory training for the support of innovative interventional clinical trials. The component ACTG Network Laboratory Center will improve scientific knowledge and technical capability by providing state-of-the-art laboratory support in the four NIH/DAIDS priority areas of strategies to cure HIV; improve the diagnosis and treatment of tuberculosis; identify strategies to cure infectious viral hepatitis; improve the treatment and prevention of non-infectious co-morbidities associated with HIV infection and evaluate novel interventions targeting HIV infection. In addition, the Laboratory Center will provide laboratory support for therapeutic studies of oral manifestations of HIV/AIDS and virally mediated cancers. The continued expansion of an effective, quality-assured laboratory program at domestic and international sites for protocol safety measures, state-of-the-art molecular assays for virology and mycobacteriology; immunology and biomarkers; pharmacology; genomics; and oral pathogens associated with HIV-1 infection, will provide the essential framework for advancing the scientific agenda of the ACTG Network. The Laboratory Center will continue to provide oversight of established specimen and human DNA repositories for the ACTG Network, harmonize specific laboratory testing and standardized operating procedures with other Networks where feasible and continue to support the laboratory training of technologists and investigators domestically and internationally.",,2023,University Of California Los Angeles,5882075,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2022 +P21587,1U01CK000666-01,Investigation of Monkeypox and Other Zoonotic Diseases in the Democratic Republic of the Congo (DRC) - 2022,"The goals of this project are to improve the scientific understanding and reduce the clinical burden of Monkeypox (MPX) and other zoonotic diseases in Democratic Republic of the Congo (DRC). This should directly support the U.S. CDC mission of strengthening public health surveillance systems globally to prevent the spread of emerging diseases. This project will rely upon the Kinshasa School of Public Health’s considerable experience with training public health practitioners, conducting scientific research trials, and supporting the DRC Ministry of Health to accomplish its objectives. The project will be framed around a laboratory-based surveillance system for MPX in DRC to collect accurate case burden data. We will expand upon this framework by evaluating new training methods for health workers, improving geographic data, and assessing new diagnostic platforms when available. We will use our relationships with health systems in highly affected areas to conduct clinical trials of care regimens, vaccines, and anti-viral therapies. We will perform serosurveys in high-risk and survivor populations to better understand transmission risk factors, viral persistence, and sequalae. We will work with key groups in these areas to identify wildlife reservoirs of MPX and collect qualitative data on the attitudes and behaviors of key populations living in these communities. We will work with the government of DRC to improve the ability to respond to outbreaks quickly by preemptively training response workers, developing health promotion networks, and responding to misinformation rapidly. We will share results with national stakeholders and other nations interested in being better prepared for responding to endemic and imported MPX cases.",,2027,KINSHASA SCHOOL OF PUBLIC HEALTH,875000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Clinical | Non-Clinical,Unspecified,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Africa,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Development of equitable, accessible, safe & effective diagnostics (including POC) | Investigation of zoonotic transmission & reservoirs | Epidemiology & transmission dynamics of mpox including sexual transmission. | Transmission dynamics including risk & determinants of acquisition | Ongoing assessment & evaluation of surveillance",Congo (DRC),,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Therapeutics research, development and implementation | Vaccines research, development and implementation | Research on Capacity Strengthening",Diagnostics | Animal source and routes of transmission | Disease surveillance & mapping | Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase) | Individual level capacity strengthening,2022 +P21588,5R21AI160063-02,Targeting of RAG-dependent and -independent innate immune responses by the Ectromelia C15 protein,"Several members of the orthopoxvirus family, including variola (the cause of smallpox) and monkeypox, pose serious threats to human health. Other members are equally severe in their natural hosts, including ectromelia (ECTV), the cause of mousepox - a disease with many similarities to smallpox. The considerable virulence of these large DNA viruses is attributable in great measure to their many proteins that impede both innate and adaptive host defenses. The largest among these immunomodulatory proteins are the B22 family members, which, despite their size and contributions to virulence, remain vastly understudied. Highly homologous B22 family members are present throughout the orthopoxviruses except for vaccinia, the attenuated orthopoxvirus that has served as the smallpox vaccine for centuries. We focus in this exploratory R21 proposal on C15, the B22 family member of ECTV. Deletion of C15 converts the virus from 100% lethal to 100% nonlethal in vivo despite having no impact on replication in vitro. Our preliminary work with C15 has revealed two novel properties: 1) C15 potently and selectively inhibits CD4+ T cell activation in a way that inhibits assembly of the immunological synapse. 2) In addition to targeting adaptive immunity, C15 also facilitates viral replication as early as 3 days post infection, reflecting inhibition of innate immunity. Remarkably, C15 interferes with both RAG-dependent and -independent components of innate immunity. Based on our preliminary data and the established literature, we hypothesize that the RAG-independent component targeted by C15 is NK cell-mediated cytolysis and the RAG- dependent component is bystander activation of memory CD8+ T cells (Trm). We further hypothesize that the molecular target linking these two cell types is NKG2D, an activating receptor expressed by both NK cells and Trm and shown previously to play an important role in defense against ECTV. Drawing from many years of poxvirus experience and a wide range of established and cutting-edge techniques, we will test these three hypotheses in three independent but complementary aims. Outcomes of this project could considerably enhance understanding of orthopoxvirus pathogenesis and, more broadly, contribute to fundamental principles of virus:host interplay. In addition, we anticipate that results will launch several subsequent projects including: a) incorporation of CD4+ T cell inhibition in future mechanistic studies, b) examination of other B22 family members and, c) the development of C15 derivatives for potential therapeutic modulation of host responses.",,2023,CHILDREN'S HOSP OF PHILADELPHIA,220000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21589,5R21AI163910-02,Unravelling the mechanisms of virus host species jump,"The mechanisms enabling cross-species jumps of viruses, for example current coronavirus SARS-CoV-2 pandemic and sporadic outbreak of monkeypox virus in Africa and USA into a new naive host species have long been a subject of scientific interest. In the case of poxviruses, it is thought to be modulated by many host range factors derived from both the host and virus. Myxoma virus (MYXV) is the causative agent of myxomatosis, a lethal disease in the European rabbit (Oryctolagus cuniculus). The introduction of MYXV to control feral European rabbit populations in Australia and Europe, in the early 1950s, presents the best-documented field example of hostâ€Â""virus co-evolution, following a cross-species transmission. In the case of MYXV, the virus is nonpathogenic in its evolutionary host (Sylvilagus sp.) but was extremely lethal immediately after it leaped into European rabbits in the late 19th century. Until recently, MYXV was only known to cause myxomatosis in European rabbits. However, in 2018, deceased wild Iberian hares with lesions consistent with those observed in myxomatosis were found in Spain, suggesting a likely recent outbreak of myxomatosis in this Iberian hare population. Our inquiry into the causative agent of these lesions resulted in the identification of a new recombinant MYXV, hereby referred to as MYXV Toledo (MYXV-Tol). The genome of this new strain is ~99 % identical to MYXV variants /strains previously reported circulating in rabbits, with the exception of the insertion of a new recombinant region ~2,800 bp in length and three disrupted genes (M009L, M036L and M152R). In this novel recombinant insertion region, a new orthologue of a poxvirus host range gene called M159 was identified, which is homologous to the poxvirus C7L-like host range factor superfamily. Our preliminary results with recombinant virus constructs confirm that M159 is the key host range protein that allowed MYXV-Tol species leap in hares. Our goal is to elucidate the mechanisms of this cross-species spillover by studying M159 functions. We thereby propose to address the following aims to investigate the mechanisms of this novel poxvirus host range protein M159 in MYXV-Tol and how it influences virus replication and virulence: Aim 1: Elucidate the biological mechanism(s) of cross-species jumping of the newly identified MYXV-Tol host range protein M159. Aim 2: Define the relevance of the new host range protein, M159, for in vivo infection and replication in a European rabbit model. This R21 proposal will enable us to gain insight into the role MYXV-Tol host range protein M159 plays on the virus replication, regulation of host immune system, and pathogenicity.",,2024,Arizona State University-Tempe Campus,196250,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Research for enhanced understanding of the disease | Viral evolution in different contexts & implications | Investigation of zoonotic transmission & reservoirs,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2021 +P21590,5R01AI151559-03,Advancement of poxvirus inhibitor,"Abstract Poxviruses are a large group of human pathogens that include the causative agent of smallpox, Monkeypox, and Cowpox. As poxvirus immunity around the world wanes there has been a concomitant increase in poxviral disease, leading to a growing need for small molecule therapeutics that protect against poxviral disease. There are several investigational drugs that have been used to treat cases of orthopoxvirus infection and one has been recently approved by the FDA for limited use, but viral resistance to this compound has been noted. The WHO, CDC and other agencies have stated a strong desire for at least two small molecule therapeutics that broadly target poxviruses due to the high perceived risk of poxviral disease both from endemic exposure as well as the potential purposeful release of smallpox as a bioterror agent. This goal has not yet been met. We have identified a family of non-nucleoside small molecules (“PDPMs”) that show broad spectrum antipoxviral activity and low/no toxicity to cells and suppress viral mRNA production. Our current data suggests is that the drug is targeting the poxvirus RNA polymerase (RNAP), which would be an ideal target that is highly conserved across all poxviruses. Through this proposal we will probe the potential of PDPMs to become effective antivirals, using medicinal chemistry approaches to identify compounds with high potency and favorable pharmacokinetic profiles. To aid and complement the therapeutic development of these molecules, we will use genetic, biochemical and chemical approaches to determine the target of the compound and the mechanism by which it blocks viral replication. Following the identification of high potency, pharmacologically favorable compounds, we will test their efficacy in animal models of poxvirus disease. These experiments will be carried out through an ongoing collaboration at the CDC. The CDC will oversee testing of PDPMs against smallpox and in efficacy determination in animal models of poxviral disease. When these efforts are completed they will enable advanced (towards first-in-human) testing of a new class of poxvirus inhibitor â€Â"" an inhibitor that has a mechanism of action complementary to the existing FDA approved compound and a broad protection profile, fulfilling the need for multi-compound protection from these significant human pathogens.",,2025,Boston University Medical Campus,593447,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21591,3R01DA049644-03S3,Epidemiologic Studies of HMPXV Infection among PWID in the US-Mexico Border Region to Inform Prevention Responses,"In response to NOT-OD-22-159, this project will leverage an ongoing cohort of people who inject drugs (PWID) in the U.S.-Mexico border region to study the epidemiology of monkeypox virus (HMPXV) to inform prevention interventions to diagnose and treat HMPXV and curtail transmission. Although it is well known that PWID face numerous health disparities including higher rates of HIV, HCV and sexually transmitted infections (STIs) than the general population, experts are concerned that the ongoing outbreak of HMPXV, which is the largest international outbreak recorded since this virus first emerged in the 1970’s, will soon disproportionately affect people experiencing homelessness (PEH), which includes a high proportion of PWID. Our team includes epidemiologists, prevention interventionists, molecular virologists and infectious disease physicians to address these aims: Aim 1. To determine the prevalence and correlates of subclinical and symptomatic HMPXV infection among PWID in the San Diego/Tijuana (SD/TJ) border region to inform the development of prevention interventions. H1. PWID who are unstably housed (H1.1), Latinx (H1.2) or living with HIV and not receiving ART (H1.3) will be significantly more likely to test positive for HMPXV infection. Aim 2. To estimate incidence and risk factors of HMPXV infection among PWID over a one-year period. H2.1 PWID who report recently having abscesses associated with injection drug use, STIs or open sores will be more likely to acquire HMPXV during follow-up. H2.2. PWID who report engaging in sex work and those with higher numbers of sex partners will be more likely to acquire HMPXV during follow-up. Aim 3. To determine network features associated with cross-border transmission of HMPXV among PWID. H3.1 Cross-border drug tourism between SD and TJ (by participants & their network contacts) will be associated with HMPXV infection. H3.2. Network-level risk factors such as total number of contacts and number of contacts who are MSM, sex workers, unstably housed, or have a history of incarceration will be independently associated with HMPXV infection after controlling for individual-level risk factors. Aim 4: To conduct phylogenomic characterization of circulating HMPXV variants in the SD/TJ region including mutation signatures (e.g., APOBEC3). H4.1 Circulating HMPXV will have a single origin (lineage B.1) followed by local dispersal. We will leverage the binational infrastructure of our NIDA- funded binational cohort of PWID, and support from a new pandemic preparedness institute at UCSD to conduct HMPXV PCR testing and sequencing on swabs collected from any suspect lesions/vesicles as well as oral and anal swabs. Serologic HMPXV testing will be done in-kind by the CDC. Findings will inform potential interventions and policies, including whether PWID and/or PEH should be recommended for routine vaccination and whether subsequent interventions to increase HMPXV testing, vaccination and treatment in this vulnerable population should be network or venue-based, following NIMHD’s conceptual model for structural interventions.",,2025,"University Of California, San Diego",379961,Human Populations,Other,Adults (18 and older),Unspecified,Drug users | Sex workers | Other,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Viral evolution in different contexts & implications | Epidemiology & transmission dynamics of mpox including sexual transmission. | Transmission dynamics including risk & determinants of acquisition | Ongoing assessment & evaluation of surveillance,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Impact/ effectiveness of control measures | Disease surveillance & mapping",2020 +P21592,75N91019D00024-P00001-759102000025-5,"A randomized, placebo-controlled trial of the safety and efficacy of tecovirimat for the treatment of patients with monkeypox virus disease","The funding supports a clinical trial to identify effective treatments for monkeypox virus disease. Monkeypox virus is a re-emerging pathogen that causes monkeypox virus disease, a disease of epidemic potential that causes significant morbidity and can result in death. Human monkeypox cases have been increasing in sub-Saharan Africa since 2000 and sporadic outbreaks outside of Africa have occurred, with cases in the US and the UK in 2021. The similarity between MPXV and the variola virus, coupled with concerns about the potential of the variola virus as a potential bioterrorism agent, have placed monkeypox treatments at the forefront of public health and scientific research agendas in many countries.",,2025,"LEIDOS BIOMEDICAL RESEARCH, INC.",9824009,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +P21593,1R13AI152363-01,"XXIII International Poxvirus, Asfarvirus, and Iridovirus Conference","This application for NIAID funding is to help support selected expenses for the 2020 XXIII International Poxvirus, Asfarvirus and Iridovirus Conference. This conference is the premier meeting in the field that brings together principal investigators, postdoctoral fellows, and students from around the world who study poxvirology and other large DNA viruses. The 2020 meeting will be held on June 26 to June 30, 2020 in Philadelphia, PA. This conference, which is held every other year, was established in 1977 with the intent to provide a collegial meeting place for scientists to exchange ideas in this important field. The meeting averages around 200 participants. While there are other more general meetings where senior principal investigators in this field present their data, the focus of this meeting is to provide a forum where graduate students and postdoctoral fellows present their work to each other and established investigators. The meeting also aims to provide the opportunity to highlight new junior faculty in the field. The majority of presentations are given by either graduate students or post-doctoral fellows in a setting of vibrant discussions where ideas are exchanged. In addition to the oral presentations, students and post-doctoral fellows have the opportunity to present their work in poster sessions. Thus, both in oral sessions and poster sessions, students and post- doctoral fellows in the field of poxvirology gain valuable experience in presenting their data, as well as contacts that will be useful for advancing their science and their careers. Historically, the meeting location alternates between North America and Europe. However, for the first time in the meeting’s history, the 2018 meeting was held in Asia. The Conference for 2020 returns to North America for the first time since 2014 (and the first time in the U.S. since 2010). The location of the 2020 meeting was chosen to allow easy travel of the national and international scientific community. Philadelphia is easily accessible by car or train, and from around the greater United States and the world via direct flights to Philadelphia International Airport. This community of scientists have been playing a key role in the US government’s efforts to develop an effective response to the public health concerns regarding smallpox, monkeypox, and other emerging poxvirus diseases. In addition, with the success of a poxvirus-based recombinant vaccines and the use of poxviruses as oncolytic agents in the treatment of cancer, there is a critical need to improve poxviruses as vaccine vectors and therapeutics. Thus, the XXIII International Poxvirus, Asfarvirus and Iridovirus Conference is extremely relevant to the scientific mission of the NIAID and will provide a venue for discussions of new understandings of the basic biology of these important viruses and how they can be translated into regimens that can improve human health and safety.",,2022,University Of Pennsylvania,3000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P21594,1R21AI160063-01,Targeting of RAG-dependent and -independent innate immune responses by the Ectromelia C15 protein,"Several members of the orthopoxvirus family, including variola (the cause of smallpox) and monkeypox, pose serious threats to human health. Other members are equally severe in their natural hosts, including ectromelia (ECTV), the cause of mousepox - a disease with many similarities to smallpox. The considerable virulence of these large DNA viruses is attributable in great measure to their many proteins that impede both innate and adaptive host defenses. The largest among these immunomodulatory proteins are the B22 family members, which, despite their size and contributions to virulence, remain vastly understudied. Highly homologous B22 family members are present throughout the orthopoxviruses except for vaccinia, the attenuated orthopoxvirus that has served as the smallpox vaccine for centuries. We focus in this exploratory R21 proposal on C15, the B22 family member of ECTV. Deletion of C15 converts the virus from 100% lethal to 100% nonlethal in vivo despite having no impact on replication in vitro. Our preliminary work with C15 has revealed two novel properties: 1) C15 potently and selectively inhibits CD4+ T cell activation in a way that inhibits assembly of the immunological synapse. 2) In addition to targeting adaptive immunity, C15 also facilitates viral replication as early as 3 days post infection, reflecting inhibition of innate immunity. Remarkably, C15 interferes with both RAG-dependent and -independent components of innate immunity. Based on our preliminary data and the established literature, we hypothesize that the RAG-independent component targeted by C15 is NK cell-mediated cytolysis and the RAG- dependent component is bystander activation of memory CD8+ T cells (Trm). We further hypothesize that the molecular target linking these two cell types is NKG2D, an activating receptor expressed by both NK cells and Trm and shown previously to play an important role in defense against ECTV. Drawing from many years of poxvirus experience and a wide range of established and cutting-edge techniques, we will test these three hypotheses in three independent but complementary aims. Outcomes of this project could considerably enhance understanding of orthopoxvirus pathogenesis and, more broadly, contribute to fundamental principles of virus:host interplay. In addition, we anticipate that results will launch several subsequent projects including: a) incorporation of CD4+ T cell inhibition in future mechanistic studies, b) examination of other B22 family members and, c) the development of C15 derivatives for potential therapeutic modulation of host responses.",,2023,CHILDREN'S HOSP OF PHILADELPHIA,264000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21595,1R21AI163910-01,Unravelling the mechanisms of virus host species jump,"The mechanisms enabling cross-species jumps of viruses, for example current coronavirus SARS-CoV-2 pandemic and sporadic outbreak of monkeypox virus in Africa and USA into a new naive host species have long been a subject of scientific interest. In the case of poxviruses, it is thought to be modulated by many host range factors derived from both the host and virus. Myxoma virus (MYXV) is the causative agent of myxomatosis, a lethal disease in the European rabbit (Oryctolagus cuniculus). The introduction of MYXV to control feral European rabbit populations in Australia and Europe, in the early 1950s, presents the best-documented field example of hostâ€Â""virus co-evolution, following a cross-species transmission. In the case of MYXV, the virus is nonpathogenic in its evolutionary host (Sylvilagus sp.) but was extremely lethal immediately after it leaped into European rabbits in the late 19th century. Until recently, MYXV was only known to cause myxomatosis in European rabbits. However, in 2018, deceased wild Iberian hares with lesions consistent with those observed in myxomatosis were found in Spain, suggesting a likely recent outbreak of myxomatosis in this Iberian hare population. Our inquiry into the causative agent of these lesions resulted in the identification of a new recombinant MYXV, hereby referred to as MYXV Toledo (MYXV-Tol). The genome of this new strain is ~99 % identical to MYXV variants /strains previously reported circulating in rabbits, with the exception of the insertion of a new recombinant region ~2,800 bp in length and three disrupted genes (M009L, M036L and M152R). In this novel recombinant insertion region, a new orthologue of a poxvirus host range gene called M159 was identified, which is homologous to the poxvirus C7L-like host range factor superfamily. Our preliminary results with recombinant virus constructs confirm that M159 is the key host range protein that allowed MYXV-Tol species leap in hares. Our goal is to elucidate the mechanisms of this cross-species spillover by studying M159 functions. We thereby propose to address the following aims to investigate the mechanisms of this novel poxvirus host range protein M159 in MYXV-Tol and how it influences virus replication and virulence: Aim 1: Elucidate the biological mechanism(s) of cross-species jumping of the newly identified MYXV-Tol host range protein M159. Aim 2: Define the relevance of the new host range protein, M159, for in vivo infection and replication in a European rabbit model. This R21 proposal will enable us to gain insight into the role MYXV-Tol host range protein M159 plays on the virus replication, regulation of host immune system, and pathogenicity.",,2023,Arizona State University-Tempe Campus,235500,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Research for enhanced understanding of the disease | Investigation of zoonotic transmission & reservoirs,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2021 +P21596,5R01AI151559-02,Advancement of poxvirus inhibitor,"Abstract Poxviruses are a large group of human pathogens that include the causative agent of smallpox, Monkeypox, and Cowpox. As poxvirus immunity around the world wanes there has been a concomitant increase in poxviral disease, leading to a growing need for small molecule therapeutics that protect against poxviral disease. There are several investigational drugs that have been used to treat cases of orthopoxvirus infection and one has been recently approved by the FDA for limited use, but viral resistance to this compound has been noted. The WHO, CDC and other agencies have stated a strong desire for at least two small molecule therapeutics that broadly target poxviruses due to the high perceived risk of poxviral disease both from endemic exposure as well as the potential purposeful release of smallpox as a bioterror agent. This goal has not yet been met. We have identified a family of non-nucleoside small molecules (“PDPMs”) that show broad spectrum antipoxviral activity and low/no toxicity to cells and suppress viral mRNA production. Our current data suggests is that the drug is targeting the poxvirus RNA polymerase (RNAP), which would be an ideal target that is highly conserved across all poxviruses. Through this proposal we will probe the potential of PDPMs to become effective antivirals, using medicinal chemistry approaches to identify compounds with high potency and favorable pharmacokinetic profiles. To aid and complement the therapeutic development of these molecules, we will use genetic, biochemical and chemical approaches to determine the target of the compound and the mechanism by which it blocks viral replication. Following the identification of high potency, pharmacologically favorable compounds, we will test their efficacy in animal models of poxvirus disease. These experiments will be carried out through an ongoing collaboration at the CDC. The CDC will oversee testing of PDPMs against smallpox and in efficacy determination in animal models of poxviral disease. When these efforts are completed they will enable advanced (towards first-in-human) testing of a new class of poxvirus inhibitor â€Â"" an inhibitor that has a mechanism of action complementary to the existing FDA approved compound and a broad protection profile, fulfilling the need for multi-compound protection from these significant human pathogens.",,2025,Boston University Medical Campus,590147,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21597,5F30AI149864-02,The novel innate immune-antagonistic effects of ectromelia virus C15 protein,"Smallpox was one of the deadliest diseases in human history, and despite its eradication, orthopxviruses continue to pose a significant public health threat due to bioterrorism concerns and zoonoses. The virulence of these viruses relies upon their evasion of host immune responses by a large arsenal of immunomodulatory proteins. One of these proteins is the C15 protein of ectromelia virus, the cause of mousepox, which significantly impacts virulence in vivo. This protein is the largest in the viral genome and has homologs in the virulent orthopoxviruses, including the agents of smallpox and monkeypox, but no homology to any protein outside this family. Previous work has shown that C15 inhibits CD4 T cell activation, but I have recently determined that C15 significantly enhances viral replication in vivo at times that precede the onset of adaptive immunity, suggesting the existence of a second innate immune targeting function. The goal of this project is to understand this novel role of C15 early in infection. Preliminary work has shown that C15 maintains its replication­promoting effect in RAG KO but not RAG IL2RG double KO mice, implying the targeting of NK cells. Further analyses indicate C15 targeting of another RAG­dependent component of the innate immune response, most likely T cells. In searching for a unifying molecular target, additional preliminary data implicates the NK gene complex; NKG2D is a receptor encoded within the NK complex that is capable of activating both NK cells and T cells. I therefore hypothesize that C15 inhibits NKG2D ­mediated recognition of infected cells by NK and T cells, thereby inhibiting immune control of viral replication. To test this hypothesis, I propose three independent and complementary specific aims, each investigating the impact of C15 on one of the three components of the hypothesis. The first aim will identify the impact of C15 on NK cell function, using a set of orthogonal in vivo and in vitro approaches. The second aim will test the hypothesis that C15 targets T cells using similarly comprehensive approaches. The third aim will test the hypothesis that C15 targets NKG2D­mediated activation of immune cells by interrogating the importance of NKG2D and its adaptors DAP10 and DAP12 for the early impact of C15 in vivo as well as the impact of C15 on expression of NKG2D ligands. The identification of separate innate and adaptive immunomodulatory functions in a single viral protein is highly unique. The proposed studies will provide insight into the exceptional virulence of the orthopoxviruses, including those of particular public health concern, and could lead to the use of this protein family as an immune targeting therapeutic strategy. ",,2022,University Of Pennsylvania,33385,Viruses,Not applicable,Not Applicable,,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21598,1R01AI151559-01,Advancement of poxvirus inhibitor,"Abstract Poxviruses are a large group of human pathogens that include the causative agent of smallpox, Monkeypox, and Cowpox. As poxvirus immunity around the world wanes there has been a concomitant increase in poxviral disease, leading to a growing need for small molecule therapeutics that protect against poxviral disease. There are several investigational drugs that have been used to treat cases of orthopoxvirus infection and one has been recently approved by the FDA for limited use, but viral resistance to this compound has been noted. The WHO, CDC and other agencies have stated a strong desire for at least two small molecule therapeutics that broadly target poxviruses due to the high perceived risk of poxviral disease both from endemic exposure as well as the potential purposeful release of smallpox as a bioterror agent. This goal has not yet been met. We have identified a family of non-nucleoside small molecules (“PDPMs”) that show broad spectrum antipoxviral activity and low/no toxicity to cells and suppress viral mRNA production. Our current data suggests is that the drug is targeting the poxvirus RNA polymerase (RNAP), which would be an ideal target that is highly conserved across all poxviruses. Through this proposal we will probe the potential of PDPMs to become effective antivirals, using medicinal chemistry approaches to identify compounds with high potency and favorable pharmacokinetic profiles. To aid and complement the therapeutic development of these molecules, we will use genetic, biochemical and chemical approaches to determine the target of the compound and the mechanism by which it blocks viral replication. Following the identification of high potency, pharmacologically favorable compounds, we will test their efficacy in animal models of poxvirus disease. These experiments will be carried out through an ongoing collaboration at the CDC. The CDC will oversee testing of PDPMs against smallpox and in efficacy determination in animal models of poxviral disease. When these efforts are completed they will enable advanced (towards first-in-human) testing of a new class of poxvirus inhibitor â€Â"" an inhibitor that has a mechanism of action complementary to the existing FDA approved compound and a broad protection profile, fulfilling the need for multi-compound protection from these significant human pathogens.",,2025,Boston University Medical Campus,575718,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21599,1F30AI149864-01A1,The novel innate immune-antagonistic effects of ectromelia virus C15 protein,"Smallpox was one of the deadliest diseases in human history, and despite its eradication, orthopxviruses continue to pose a significant public health threat due to bioterrorism concerns and zoonoses. The virulence of these viruses relies upon their evasion of host immune responses by a large arsenal of immunomodulatory proteins. One of these proteins is the C15 protein of ectromelia virus, the cause of mousepox, which significantly impacts virulence in vivo. This protein is the largest in the viral genome and has homologs in the virulent orthopoxviruses, including the agents of smallpox and monkeypox, but no homology to any protein outside this family. Previous work has shown that C15 inhibits CD4 T cell activation, but I have recently determined that C15 significantly enhances viral replication in vivo at times that precede the onset of adaptive immunity, suggesting the existence of a second innate immune targeting function. The goal of this project is to understand this novel role of C15 early in infection. Preliminary work has shown that C15 maintains its replication­promoting effect in RAG KO but not RAG IL2RG double KO mice, implying the targeting of NK cells. Further analyses indicate C15 targeting of another RAG­dependent component of the innate immune response, most likely T cells. In searching for a unifying molecular target, additional preliminary data implicates the NK gene complex; NKG2D is a receptor encoded within the NK complex that is capable of activating both NK cells and T cells. I therefore hypothesize that C15 inhibits NKG2D ­mediated recognition of infected cells by NK and T cells, thereby inhibiting immune control of viral replication. To test this hypothesis, I propose three independent and complementary specific aims, each investigating the impact of C15 on one of the three components of the hypothesis. The first aim will identify the impact of C15 on NK cell function, using a set of orthogonal in vivo and in vitro approaches. The second aim will test the hypothesis that C15 targets T cells using similarly comprehensive approaches. The third aim will test the hypothesis that C15 targets NKG2D­mediated activation of immune cells by interrogating the importance of NKG2D and its adaptors DAP10 and DAP12 for the early impact of C15 in vivo as well as the impact of C15 on expression of NKG2D ligands. The identification of separate innate and adaptive immunomodulatory functions in a single viral protein is highly unique. The proposed studies will provide insight into the exceptional virulence of the orthopoxviruses, including those of particular public health concern, and could lead to the use of this protein family as an immune targeting therapeutic strategy. ",,2022,University Of Pennsylvania,32869,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21603,1R21AI174041-01,Oral Antivirals against COVID-19 and Clinical Outcomes in High Risk Populations,"COVID-19 has led to over 350 million reported cases and over 5.6 million resulting deaths globally, and nearly 72 million cases and >900,000 deaths in the US. Highly effective vaccines are now available and are the first line of defense. However, immunity wanes off over time and breakthrough infections in fully vaccinated persons have been reported, particularly with the newer variants. In December 2021, two novel oral antiviral agents, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV), were granted Emergency Use Authorization (EUA) by the FDA for treatment of early symptomatic patients with mild to moderate COVID-19 at high risk of progression to severe disease. These authorizations were granted based on limited published data, and critical questions about their comparative effectiveness, effectiveness in the real-world settings, and effectiveness in specific high-risk sub-populations remain to be answered. There is an urgent need to understand the real-world effectiveness of these drugs, especially in the high-risk and vulnerable populations, as well as longer term clinical outcomes in treated patients. Such knowledge is essential for the patients, providers, payors, and policymakers, to ensure that they are used only in the appropriate populations and situations based on strong clinical evidence. To address these critical gaps in knowledge, we propose the following hypotheses: Hypothesis 1: Treatment with NMV/r or MPV will be associated with a significant reduction in COVID-19 related hospitalization and 30-day all-cause mortality in older persons, those with a high comorbidity burden, and in socially vulnerable persons. Hypothesis 2: We hypothesize that NMV/r and MPV treatment will be associated with a significant reduction in subsequent hospital admissions, emergency department visits, and outpatient clinic visits over a 1-year period after recovery. Treatment will also be associated with a lower incidence of acute myocardial infarction, stroke, decline in renal function, and diabetes, compared with propensity-score matched untreated persons. We will use the Department of Veterans Affairs’ COVID-19 Shared Data Resource (VA ORDCOVID) which contains extensive demographic, clinical, pharmacologic, laboratory, vital signs and clinical outcomes information derived from multiple validated sources. We will compare those treated with NMV/r or MPV with propensity-score matched untreated controls, matched on demographics, clinical variables, severity of presenting illness, geographic location, time of treatment, vaccination status, time from completion of a full course of vaccination, and booster dose administration. The PI, Dr. Butt has extensive experience in creating and analysing large national databases and has published 45 papers on COVID-19 in journals including the New England Journal of Medicine, Annals of Internal Medicine, JAMA Internal Medicine, Journal of Clinical Investigation, Nature Medicine, and others. He already has IRB approval to study the epidemiology, natural history, and clinical outcomes of SARS-CoV-2 infection in the VA population.",,2025,VETERANS HEALTH FOUNDATION,157813,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2023 +P21615,5R01AI152207-04,Preclinical Development of a Crimean-Congo Hemorrhagic Fever Virus Vaccine,"PROJECT SUMMARY/ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne emerging pathogen that causes severe and often fatal hemorrhagic fever in humans across a broad geographic range that includes more than 30 countries. The NIAID lists CCHFV as a Category A priority pathogen, a biological agent that poses the highest risk to national security and public health. CCHF is of particular importance to public health as there are no licensed vaccines or treatments available for use in humans, and because of the concern that the virus could be used as an agent of biological terrorism. The goal of this project is to advance the development of a recombinant vaccine based on next generation vesicular stomatitis virus (rVSV) vectors expressing the CCHFV glycoprotein as a potential medical countermeasure that can provide protection across all six genetically distinct clades of CCHFV. This application proposes to develop and pre-clinically validate a rVSV vectored CCHF vaccine. Next generation VesiculovaxâÂ""¢ CCHF vaccines will be compared head-to-head with a prototype rVSV vaccine that has been shown to completely protect animals against lethal CCHFV infection. Vaccines will be compared for immunogenicity, lack of neurovirulence, and the ability to protect STAT-1 knockout mice against all six M segment clades of CCHFV. A lead candidate vaccine will then be down selected. Supporting studies using a newly developed lethal nonhuman primate model of CCHFV will be employed to confirm protective efficacy of the lead vaccine candidate, assess the ability to the vaccine to provide rapid protection, and finally to begin to determine correlates of protection. This proposal will draw together expertise in vaccine development, CCHFV biology, and animal modeling needed to develop a vaccine that meets both the outbreak and bioweapon scenarios that require rapid protection against all CCHFV clades with a single administration.",,2025,University Of Texas Med Br Galveston,739915,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21616,5R01AI151006-04,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,318922,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Vaccine design and administration",2020 +P21617,3R01AI151006-04S1,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,79125,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Adverse events associated with immunization",2020 +P21618,3R01AI151006-03S2,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,79208,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Vaccine design and administration",2020 +P21619,5R01AI167048-03,"US-UK Collab: Modelling reassortment at the cellular, clinical, and phylogenetic level in emerging Bunyaviruses","Genome segmentation has important implications for viral gene expression control and RNA assembly into nascent virions. It also creates the potential for reassortment: the exchange of intact gene segments between viruses that coinfect the same cell. Reassortment is different from recombination since it allows many distinct genotypes to emerge from a single coinfected cell. Not only does segmentation enhance genetic diversification but it plays a unique role in the evolutionary history of segmented viruses due to the rare occasions when a reassortant is successful at a population scale. A striking example from the Bunyaviridae family of the emergence of a novel virus through reassortment is that of Ngari virus. For influenza A (IAV), the best characterised segmented virus, reassortment has facilitated the formation of pandemic strains in 1957, 1968 and 2009. Out of seven epidemic-prone diseases prioritized by the WHO 2018 R&D Blueprint as public health emergencies with an urgent need for accelerated research, three are Bunyaviruses: Lassa, Rift Valley and Crimean-Congo hemorrhagic fevers. Thus, the overarching hypothesis of this project is that reassortment of segmented viruses plays a major role not only to drive their diversification and evolution, but to dramatically alter their ecology and transmission dynamics. Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses to quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised sequencing protocols and novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV). A biobank with clinical and field samples from CCHFV endemic regions in Turkey and Tajikistan will be set up in this project. Clinical and field data will be leveraged to ensure our methods and results have the potential to inform public health strategies, predict outbreak risk and contribute to the One Health approach for the prevention and control of CCHF disease.",,2026,"TRIAD NATIONAL SECURITY, LLC",447570,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2021 +P21620,5R01AI152207-03,Preclinical Development of a Crimean-Congo Hemorrhagic Fever Virus Vaccine,"PROJECT SUMMARY/ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne emerging pathogen that causes severe and often fatal hemorrhagic fever in humans across a broad geographic range that includes more than 30 countries. The NIAID lists CCHFV as a Category A priority pathogen, a biological agent that poses the highest risk to national security and public health. CCHF is of particular importance to public health as there are no licensed vaccines or treatments available for use in humans, and because of the concern that the virus could be used as an agent of biological terrorism. The goal of this project is to advance the development of a recombinant vaccine based on next generation vesicular stomatitis virus (rVSV) vectors expressing the CCHFV glycoprotein as a potential medical countermeasure that can provide protection across all six genetically distinct clades of CCHFV. This application proposes to develop and pre-clinically validate a rVSV vectored CCHF vaccine. Next generation VesiculovaxâÂ""¢ CCHF vaccines will be compared head-to-head with a prototype rVSV vaccine that has been shown to completely protect animals against lethal CCHFV infection. Vaccines will be compared for immunogenicity, lack of neurovirulence, and the ability to protect STAT-1 knockout mice against all six M segment clades of CCHFV. A lead candidate vaccine will then be down selected. Supporting studies using a newly developed lethal nonhuman primate model of CCHFV will be employed to confirm protective efficacy of the lead vaccine candidate, assess the ability to the vaccine to provide rapid protection, and finally to begin to determine correlates of protection. This proposal will draw together expertise in vaccine development, CCHFV biology, and animal modeling needed to develop a vaccine that meets both the outbreak and bioweapon scenarios that require rapid protection against all CCHFV clades with a single administration.",,2025,University Of Texas Med Br Galveston,740027,Animals,Not applicable,Not Applicable,Unspecified | Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21621,5R44AI157650-02,"PANDAA for universal, pan-lineage molecular detection of Crimean-Congo Hemorrhagic Fever virus","Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne disease with high mortality rates in humans and high outbreak potential. Found in 30 countries across Europe, Asia, and Africa, CCHF has an extremely widespread and growing range. Its causative agent, CCHF virus (CCHFV), is listed among the urgently concerning pathogens prioritized in the WHO R&D Blueprint. With at least seven regional clades, CCHFV detection by gold standard qPCR- based methods has been encumbered by significant strain-associated genetic variability. Existing tests for CCHFV are often limited to regional use, presenting a barrier to standardization and quality assurance. The WHO has called for the development of universal CCHFV diagnostics as a global priority. Aldatu Biosciences has pioneered the use of PANDAA technology, which enables probe-based qPCR for target detection in highly variable genomic regions by simultaneously adapting and amplifying diverse templates. PANDAA uniquely mitigates the presence of target- proximal polymorphisms to allow otherwise divergent templates to be detected with consensus fluorescent probes with similar sensitivities. As such, PANDAA-enabled qPCR is an ideal solution for universal detection of pathogens with significant strain, lineage, and/or sub-type sequence diversity. Aldatu Biosciences is uniquely positioned to deliver a rapid pan-lineage qPCR-based CCHFV diagnostic. PANDAA has been successfully applied to subtype- independent detection of more than fifteen drug resistance mutation (DRM) targets in HIV. Recently, we completed development of the first pan-lineage assay for Lassa fever virus (LASV), another WHO priority pathogen with high outbreak potential. We propose to leverage the unique capabilities of PANDAA to develop a rapid, sensitive molecular diagnostic assay for CCHFV detection, and the first with pan-lineage coverage, through the following specific aims: (1) development of a pan-lineage PANDAA-CCHFV assay, leveraging proven techniques and proprietary PANDAA reagent design; (2) analytical validation of the PANDAA-CCHFV assay, including confirmation of clade inclusivity and high specificity; (3) thermostabilization of the PANDAA-CCHFV assay, in order to meet the requirements of diagnostics targeted to LMICs; (4) clinical validation of the lyophilized PANDAA-CCHFV assay, using clinical samples representing a broad variety of circulating clades and geographies; and (5) multi-site evaluation of the PANDAA qDx CCHFV test kit at reference labs at CDC- and WHO-affiliated partner institutions. As the first pan- lineage assay, PANDAA-CCHFV will provide a rapid, standardized testing option for all regions within the broad range of CCHFV. This novel, pan-lineage detection assay could ultimately be deployed in any endemic region on pre-existing qPCR equipment in central labs, and/or integrated into a closed, point-of-care system with sample processing to radically improve the CCHFV diagnostic workflow.",,2023,"ALDATU BIOSCIENCES, INC.",829151,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P21622,5R01AI151006-03,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,303068,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Vaccine design and administration",2020 +P21623,3R01AI151006-03S1,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,233250,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Vaccine design and administration",2020 +P21624,5R01AI167048-02,"US-UK Collab: Modelling reassortment at the cellular, clinical, and phylogenetic level in emerging Bunyaviruses","Genome segmentation has important implications for viral gene expression control and RNA assembly into nascent virions. It also creates the potential for reassortment: the exchange of intact gene segments between viruses that coinfect the same cell. Reassortment is different from recombination since it allows many distinct genotypes to emerge from a single coinfected cell. Not only does segmentation enhance genetic diversification but it plays a unique role in the evolutionary history of segmented viruses due to the rare occasions when a reassortant is successful at a population scale. A striking example from the Bunyaviridae family of the emergence of a novel virus through reassortment is that of Ngari virus. For influenza A (IAV), the best characterised segmented virus, reassortment has facilitated the formation of pandemic strains in 1957, 1968 and 2009. Out of seven epidemic-prone diseases prioritized by the WHO 2018 R&D Blueprint as public health emergencies with an urgent need for accelerated research, three are Bunyaviruses: Lassa, Rift Valley and Crimean-Congo hemorrhagic fevers. Thus, the overarching hypothesis of this project is that reassortment of segmented viruses plays a major role not only to drive their diversification and evolution, but to dramatically alter their ecology and transmission dynamics. Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses to quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised sequencing protocols and novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV). A biobank with clinical and field samples from CCHFV endemic regions in Turkey and Tajikistan will be set up in this project. Clinical and field data will be leveraged to ensure our methods and results have the potential to inform public health strategies, predict outbreak risk and contribute to the One Health approach for the prevention and control of CCHF disease.",,2026,"TRIAD NATIONAL SECURITY, LLC",447570,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Bunyaviridae,,,,,,,,,Lassa fever | Crimean-Congo haemorrhagic fever | Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2021 +P21625,5R01AI152207-02,Preclinical Development of a Crimean-Congo Hemorrhagic Fever Virus Vaccine,"PROJECT SUMMARY/ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne emerging pathogen that causes severe and often fatal hemorrhagic fever in humans across a broad geographic range that includes more than 30 countries. The NIAID lists CCHFV as a Category A priority pathogen, a biological agent that poses the highest risk to national security and public health. CCHF is of particular importance to public health as there are no licensed vaccines or treatments available for use in humans, and because of the concern that the virus could be used as an agent of biological terrorism. The goal of this project is to advance the development of a recombinant vaccine based on next generation vesicular stomatitis virus (rVSV) vectors expressing the CCHFV glycoprotein as a potential medical countermeasure that can provide protection across all six genetically distinct clades of CCHFV. This application proposes to develop and pre-clinically validate a rVSV vectored CCHF vaccine. Next generation VesiculovaxâÂ""¢ CCHF vaccines will be compared head-to-head with a prototype rVSV vaccine that has been shown to completely protect animals against lethal CCHFV infection. Vaccines will be compared for immunogenicity, lack of neurovirulence, and the ability to protect STAT-1 knockout mice against all six M segment clades of CCHFV. A lead candidate vaccine will then be down selected. Supporting studies using a newly developed lethal nonhuman primate model of CCHFV will be employed to confirm protective efficacy of the lead vaccine candidate, assess the ability to the vaccine to provide rapid protection, and finally to begin to determine correlates of protection. This proposal will draw together expertise in vaccine development, CCHFV biology, and animal modeling needed to develop a vaccine that meets both the outbreak and bioweapon scenarios that require rapid protection against all CCHFV clades with a single administration.",,2025,University Of Texas Med Br Galveston,642313,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P21626,1R44AI157650-01,"PANDAA for universal, pan-lineage molecular detection of Crimean-Congo Hemorrhagic Fever virus","Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne disease with high mortality rates in humans and high outbreak potential. Found in 30 countries across Europe, Asia, and Africa, CCHF has an extremely widespread and growing range. Its causative agent, CCHF virus (CCHFV), is listed among the urgently concerning pathogens prioritized in the WHO R&D Blueprint. With at least seven regional clades, CCHFV detection by gold standard qPCR- based methods has been encumbered by significant strain-associated genetic variability. Existing tests for CCHFV are often limited to regional use, presenting a barrier to standardization and quality assurance. The WHO has called for the development of universal CCHFV diagnostics as a global priority. Aldatu Biosciences has pioneered the use of PANDAA technology, which enables probe-based qPCR for target detection in highly variable genomic regions by simultaneously adapting and amplifying diverse templates. PANDAA uniquely mitigates the presence of target- proximal polymorphisms to allow otherwise divergent templates to be detected with consensus fluorescent probes with similar sensitivities. As such, PANDAA-enabled qPCR is an ideal solution for universal detection of pathogens with significant strain, lineage, and/or sub-type sequence diversity. Aldatu Biosciences is uniquely positioned to deliver a rapid pan-lineage qPCR-based CCHFV diagnostic. PANDAA has been successfully applied to subtype- independent detection of more than fifteen drug resistance mutation (DRM) targets in HIV. Recently, we completed development of the first pan-lineage assay for Lassa fever virus (LASV), another WHO priority pathogen with high outbreak potential. We propose to leverage the unique capabilities of PANDAA to develop a rapid, sensitive molecular diagnostic assay for CCHFV detection, and the first with pan-lineage coverage, through the following specific aims: (1) development of a pan-lineage PANDAA-CCHFV assay, leveraging proven techniques and proprietary PANDAA reagent design; (2) analytical validation of the PANDAA-CCHFV assay, including confirmation of clade inclusivity and high specificity; (3) thermostabilization of the PANDAA-CCHFV assay, in order to meet the requirements of diagnostics targeted to LMICs; (4) clinical validation of the lyophilized PANDAA-CCHFV assay, using clinical samples representing a broad variety of circulating clades and geographies; and (5) multi-site evaluation of the PANDAA qDx CCHFV test kit at reference labs at CDC- and WHO-affiliated partner institutions. As the first pan- lineage assay, PANDAA-CCHFV will provide a rapid, standardized testing option for all regions within the broad range of CCHFV. This novel, pan-lineage detection assay could ultimately be deployed in any endemic region on pre-existing qPCR equipment in central labs, and/or integrated into a closed, point-of-care system with sample processing to radically improve the CCHFV diagnostic workflow.",,2023,"ALDATU BIOSCIENCES, INC.",865501,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P21627,7R01AI151006-02,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2025,University Of California Riverside,331016,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity",2020 +P21628,1R01AI167048-01,"US-UK Collab: Modelling reassortment at the cellular, clinical, and phylogenetic level in emerging Bunyaviruses","Genome segmentation has important implications for viral gene expression control and RNA assembly into nascent virions. It also creates the potential for reassortment: the exchange of intact gene segments between viruses that coinfect the same cell. Reassortment is different from recombination since it allows many distinct genotypes to emerge from a single coinfected cell. Not only does segmentation enhance genetic diversification but it plays a unique role in the evolutionary history of segmented viruses due to the rare occasions when a reassortant is successful at a population scale. A striking example from the Bunyaviridae family of the emergence of a novel virus through reassortment is that of Ngari virus. For influenza A (IAV), the best characterised segmented virus, reassortment has facilitated the formation of pandemic strains in 1957, 1968 and 2009. Out of seven epidemic-prone diseases prioritized by the WHO 2018 R&D Blueprint as public health emergencies with an urgent need for accelerated research, three are Bunyaviruses: Lassa, Rift Valley and Crimean-Congo hemorrhagic fevers. Thus, the overarching hypothesis of this project is that reassortment of segmented viruses plays a major role not only to drive their diversification and evolution, but to dramatically alter their ecology and transmission dynamics. Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses to quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised sequencing protocols and novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV). A biobank with clinical and field samples from CCHFV endemic regions in Turkey and Tajikistan will be set up in this project. Clinical and field data will be leveraged to ensure our methods and results have the potential to inform public health strategies, predict outbreak risk and contribute to the One Health approach for the prevention and control of CCHF disease.",,2026,"TRIAD NATIONAL SECURITY, LLC",455718,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2021 +P21629,1R01AI152207-01,Preclinical Development of a Crimean-Congo Hemorrhagic Fever Virus Vaccine,"PROJECT SUMMARY/ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne emerging pathogen that causes severe and often fatal hemorrhagic fever in humans across a broad geographic range that includes more than 30 countries. The NIAID lists CCHFV as a Category A priority pathogen, a biological agent that poses the highest risk to national security and public health. CCHF is of particular importance to public health as there are no licensed vaccines or treatments available for use in humans, and because of the concern that the virus could be used as an agent of biological terrorism. The goal of this project is to advance the development of a recombinant vaccine based on next generation vesicular stomatitis virus (rVSV) vectors expressing the CCHFV glycoprotein as a potential medical countermeasure that can provide protection across all six genetically distinct clades of CCHFV. This application proposes to develop and pre-clinically validate a rVSV vectored CCHF vaccine. Next generation VesiculovaxâÂ""¢ CCHF vaccines will be compared head-to-head with a prototype rVSV vaccine that has been shown to completely protect animals against lethal CCHFV infection. Vaccines will be compared for immunogenicity, lack of neurovirulence, and the ability to protect STAT-1 knockout mice against all six M segment clades of CCHFV. A lead candidate vaccine will then be down selected. Supporting studies using a newly developed lethal nonhuman primate model of CCHFV will be employed to confirm protective efficacy of the lead vaccine candidate, assess the ability to the vaccine to provide rapid protection, and finally to begin to determine correlates of protection. This proposal will draw together expertise in vaccine development, CCHFV biology, and animal modeling needed to develop a vaccine that meets both the outbreak and bioweapon scenarios that require rapid protection against all CCHFV clades with a single administration.",,2025,University Of Texas Med Br Galveston,670889,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P21630,1R01AI151006-01A1,Origin of the innate immunity suppression caused by nairovirus' protease activity,"Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever, prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5- 80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities. Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other nairoviruses have been found to be sensitive to species-species variations in ISG15 and their specificity includes at least the species that disease is most prominently identified. This proposal will determine the identity of specific host proteins within those pathways targeted by vOTUs. This will enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight into the role of vOTUs play in pathogenesis and host restriction as well as advance the development of prophylactics targeting vOTUs.",,2021,University Of Georgia,351208,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Prophylactic use of treatments | Vaccine design and administration",2020 +P21635,5R01AI150917-04,"Safety and immunogenicity of a novel Rift Valley fever candidate vaccine, RVax-1","Summary / Abstract (Updated) Project Summary/Abstract. Rift Valley fever (RVF), a mosquito-borne zoonotic viral disease affecting ruminants and humans endemic to sub-Saharan Africa, Egypt, Saudi Arabia and Yemen, is classified as Category A Priority Pathogen by the NIH/NIAID and the Blueprint priority disease by the World Health Organization. With One Health approach, a control of infected animals and mosquitoes are important to eradicate RVF from specific areas, whereas vaccinated humans will support overall activities including the handling of infected animals. There are, however, no licensed RVF vaccines for human use. Live attenuated MP-12 vaccine, which was conditionally licensed in 2013 as a veterinary RVF vaccine in the U.S., had Investigational New Drug (IND) vaccine status, it has now been replaced with weakly immunogenic inactivated RVF candidate vaccine under IND. To develop a highly immunogenic and safe RVF candidate vaccine for human use, we have generated a novel live-attenuated candidate vaccine for RVF, termed “RVax-1”, which encodes more than 500 silent mutations throughout the open reading frame and a truncation of 78kD/NSm genes. Our central hypothesis is that the RVax-1 candidate vaccine is highly immunogenic in mice and sheep via the intramuscular route with a single dose, highly attenuated in pregnant rat placenta and in infant mice and disseminate poorly in mosquito vectors. The overall objective is to characterize the immunogenicity, safety, and efficacy of the RVax-1 candidate vaccine in mice, rats, and sheep, and to determine the level of viral dissemination in mosquitoes, in order to fill the gaps in knowledge regarding this candidate vaccine and move forward into IND-enabling preclinical and, subsequently, clinical evaluation. The work environment is ideal because the high containment facilities at the University of Texas Medical Branch are suitable for animal experiments, while SUNY Upstate Medical University and Kansas State University support mosquito and sheep experiments, respectively. The long-term goal of our study is to move the RVax-1 vaccine forward into preclinical evaluation, production under Good Manufacturing Practice, and Phase 1/2 trials. Specific Aim 1: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a mouse model. Specific Aim 2: To characterize the mosquito dissemination of RVax-1. Specific Aim 3: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a sheep model. Specific Aim 4: To characterize the attenuation of RVax-1 in rodent placenta. Successful completion of proposed project will qualify RVax-1 for further characterization in preclinical and clinical evaluation.",,2025,University Of Texas Med Br Galveston,386125,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21637,5R01AI150792-03,Live-attenuated Rift Valley fever vaccines: comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne zoonotic pathogen Rift Valley fever virus (RVFV). The consequences of this emerging virus could be exacerbated by insufficient vaccines for prevention of infection and disease. RVF is an important agroeconomic illness of domesticated livestock and is endemic in Africa and parts of the Middle East. Further spread is likely given that mosquito species capable of transmitting RVFV are found in Europe and the Americas. The most striking feature of RVF disease in sheep is a wave of fetal loss (known as an “abortion storm”) that sweeps through herds of pregnant animals, where spontaneous abortion rates can reach as high as 90%. Vaccination of livestock protects animals while simultaneously reducing the spread of RVFV to people. Obstacles in the successful development of RVFV livestock vaccines include: 1) vaccine strains often cause fetal infection and death in pregnant animals, and 2) vaccines that protect adult animals from disease are not always effective at preventing vertical transmission during pregnancy. These hurdles represent a major gap in the vaccine development field. The mechanisms by which live-attenuated vaccine strains of RVFV are vertically transmitted in utero, as well as the maternal immune response required for the protection of developing fetuses, are not known. No systematic evaluation of the vertical transmission potential of clinically- relevant live attenuated vaccines has been performed. To address this gap in the field, we propose to use an experimental rodent model of RVFV vertical transmission and fetal death in late-gestation pregnant rats. RVFV directly infects the placenta in rats, causes hemorrhage and inflammation, and results in fetal malformations including intrauterine fetal death even in pregnant dams without signs of disease. This proposal will use the pregnant rat model to test current RVF vaccine candidates for the mechanism(s) of vertical transmission, fetal protection, and identification of maternal immune correlates of fetal protection. We will also conduct a comparative analysis of virulent and attenuated RVFV strains for permissivity of placental explants from relevant species to identify cellular and structural targets of infection. Our overall hypothesis is that infection of pregnant rats with RVFV live-attenuated vaccines will provide pre-clinical quantitative data on vaccine safety for developing fetuses, efficacy for the fetuses, and critical maternal correlates of fetal protection. Completion of these studies will change the paradigm of RVFV vaccine development by providing, for the first time, a mechanistic explanation for the vertical transmission potential of clinically relevant LAVs.",,2026,University Of Pittsburgh At Pittsburgh,632888,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21645,5R01AI150917-03,"Safety and immunogenicity of a novel Rift Valley fever candidate vaccine, RVax-1","Specific Aims Rift Valley fever (RVF), a mosquito-borne zoonotic viral disease affecting ruminants and humans endemic to sub-Saharan Africa, Egypt, Saudi Arabia and Yemen, is classified as Category A Priority Pathogen by the NIH/NIAID and the Blueprint priority disease by the World Health Organization. With One Health approach, a control of infected animals and mosquitoes are important to eradicate RVF from specific areas, whereas vaccinated humans will support overall activities including the handling of infected animals. There are, however, no licensed RVF vaccines for human use. Live-attenuated MP-12 vaccine, which was conditionally licensed in 2013 as a veterinary RVF vaccine in the U.S., had Investigational New Drug (IND) vaccine status, it has now been replaced with weakly immunogenic inactivated RVF candidate vaccine under IND. To develop a highly immunogenic and safe RVF candidate vaccine for human use, we have generated a novel live-attenuated candidate vaccine for RVF, termed “RVax-1”, which encodes more than 500 silent mutations throughout the open reading frame and a truncation of 78kD/NSm genes. Our central hypothesis is that the RVax-1 candidate vaccine is highly immunogenic in mice and marmosets via the intramuscular route with a single dose, highly attenuated in pregnant rat placenta and in infant mice, and disseminate poorly in mosquito vectors. The overall objective is characterize the immunogenicity, safety, and efficacy of the RVax-1 candidate vaccine in mice, rats, and marmosets, and to determine the level of viral dissemination in mosquitoes, in order to fill the gaps in knowledge regarding this candidate vaccine and move forward into IND-enabling preclinical and, subsequently, clinical evaluation. The work environment is ideal because the high containment facilities at the University of Texas Medical Branch are suitable for animal experiments, and SUNY Upstate Medical University supports mosquito experiments. The long-term goal of our study is to move the RVax-1 vaccine forward into preclinical evaluation, production under Good Manufacturing Practice, and Phase 1/2 trials. Specific Aim 1: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a mouse model. Specific Aim 2: To characterize the mosquito dissemination of RVax-1. Specific Aim 3: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a marmoset model. Specific Aim 4: To characterize the attenuation of RVax-1 in rat placenta. Successful completion of proposed project will qualify RVax-1 for further characterization in preclinical and clinical evaluation.",,2025,University Of Texas Med Br Galveston,386125,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Animal and environmental research and research on diseases vectors",Pre-clinical studies | Animal source and routes of transmission,2020 +P21647,3R01AI150792-02S1,Live-attenuated Rift Valley fever vaccines: comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne zoonotic pathogen Rift Valley fever virus (RVFV). The consequences of this emerging virus could be exacerbated by insufficient vaccines for prevention of infection and disease. RVF is an important agroeconomic illness of domesticated livestock and is endemic in Africa and parts of the Middle East. Further spread is likely given that mosquito species capable of transmitting RVFV are found in Europe and the Americas. The most striking feature of RVF disease in sheep is a wave of fetal loss (known as an “abortion storm”) that sweeps through herds of pregnant animals, where spontaneous abortion rates can reach as high as 90%. Vaccination of livestock protects animals while simultaneously reducing the spread of RVFV to people. Obstacles in the successful development of RVFV livestock vaccines include: 1) vaccine strains often cause fetal infection and death in pregnant animals, and 2) vaccines that protect adult animals from disease are not always effective at preventing vertical transmission during pregnancy. These hurdles represent a major gap in the vaccine development field. The mechanisms by which live-attenuated vaccine strains of RVFV are vertically transmitted in utero, as well as the maternal immune response required for the protection of developing fetuses, are not known. No systematic evaluation of the vertical transmission potential of clinically- relevant live attenuated vaccines has been performed. To address this gap in the field, we propose to use an experimental rodent model of RVFV vertical transmission and fetal death in late-gestation pregnant rats. RVFV directly infects the placenta in rats, causes hemorrhage and inflammation, and results in fetal malformations including intrauterine fetal death even in pregnant dams without signs of disease. This proposal will use the pregnant rat model to test current RVF vaccine candidates for the mechanism(s) of vertical transmission, fetal protection, and identification of maternal immune correlates of fetal protection. We will also conduct a comparative analysis of virulent and attenuated RVFV strains for permissivity of placental explants from relevant species to identify cellular and structural targets of infection. Our overall hypothesis is that infection of pregnant rats with RVFV live-attenuated vaccines will provide pre-clinical quantitative data on vaccine safety for developing fetuses, efficacy for the fetuses, and critical maternal correlates of fetal protection. Completion of these studies will change the paradigm of RVFV vaccine development by providing, for the first time, a mechanistic explanation for the vertical transmission potential of clinically relevant LAVs.",,2026,University Of Pittsburgh At Pittsburgh,483301,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21648,5R21AI163603-02,Role of the novel entry factor Lrp1 in in vivo tropism and pathogenesis of Rift Valley fever virus,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne Rift Valley fever virus (RVFV). RVF is an important disease of domesticated livestock that is zoonotically transmitted to people, where it causes a spectrum of illness from mild to lethal. The significance of RVFV is highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of Priority Diseases, emphasizing the potential impact of RVFV on the global health and economy. Little is known about the entry factors that RVFV uses to infect cells from multiple species. Our rigorous and convincing preliminary data identify a cell surface receptor in the host lipid metabolism pathway that mediates infection of cells by RVFV. This proposal will determine the biological significance of this lipid receptor protein in RVFV disease in mice through conditional knockouts in cell types that are relevant to RVFV infection, including hepatocytes, neurons, and myeloid cells. We will use transient and genetic tissue-specific conditional gene knockouts of the lipid receptor generated using the Cre/Lox system. We hypothesize that eliminating lipid receptor expression in the liver will rescue mice from an otherwise highly lethal infection. We further hypothesize that conditional and tissue-specific gene deletions of the lipid receptor in mice will limit RVFV-associated pathogenic outcomes, including hepatic disease and encephalitis. Our highly collaborative and synergistic team is led by Dr. Amy Hartman (PI), an expert in the pathogenesis of RVFV, and by Dr. Gaya Amarasinghe (Co-I), a biochemist and biophysicist with expertise in host-pathogen interactions. This R21 proposal presents an opportunity to expand upon our collaborative efforts to determine the biological relevance of the RVFV-lipid receptor interaction in the mouse model. Completion of this proposal will have high impact on the field because it is the first in vivo assessment of receptor usage by RVFV. All reagents are available including mouse strains, viruses, and techniques; thus, the feasibility is high.",,2023,University Of Pittsburgh At Pittsburgh,195050,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P21652,5R01AI150917-02,"Safety and immunogenicity of a novel Rift Valley fever candidate vaccine, RVax-1","Specific Aims Rift Valley fever (RVF), a mosquito-borne zoonotic viral disease affecting ruminants and humans endemic to sub-Saharan Africa, Egypt, Saudi Arabia and Yemen, is classified as Category A Priority Pathogen by the NIH/NIAID and the Blueprint priority disease by the World Health Organization. With One Health approach, a control of infected animals and mosquitoes are important to eradicate RVF from specific areas, whereas vaccinated humans will support overall activities including the handling of infected animals. There are, however, no licensed RVF vaccines for human use. Live-attenuated MP-12 vaccine, which was conditionally licensed in 2013 as a veterinary RVF vaccine in the U.S., had Investigational New Drug (IND) vaccine status, it has now been replaced with weakly immunogenic inactivated RVF candidate vaccine under IND. To develop a highly immunogenic and safe RVF candidate vaccine for human use, we have generated a novel live-attenuated candidate vaccine for RVF, termed “RVax-1”, which encodes more than 500 silent mutations throughout the open reading frame and a truncation of 78kD/NSm genes. Our central hypothesis is that the RVax-1 candidate vaccine is highly immunogenic in mice and marmosets via the intramuscular route with a single dose, highly attenuated in pregnant rat placenta and in infant mice, and disseminate poorly in mosquito vectors. The overall objective is characterize the immunogenicity, safety, and efficacy of the RVax-1 candidate vaccine in mice, rats, and marmosets, and to determine the level of viral dissemination in mosquitoes, in order to fill the gaps in knowledge regarding this candidate vaccine and move forward into IND-enabling preclinical and, subsequently, clinical evaluation. The work environment is ideal because the high containment facilities at the University of Texas Medical Branch are suitable for animal experiments, and SUNY Upstate Medical University supports mosquito experiments. The long-term goal of our study is to move the RVax-1 vaccine forward into preclinical evaluation, production under Good Manufacturing Practice, and Phase 1/2 trials. Specific Aim 1: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a mouse model. Specific Aim 2: To characterize the mosquito dissemination of RVax-1. Specific Aim 3: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a marmoset model. Specific Aim 4: To characterize the attenuation of RVax-1 in rat placenta. Successful completion of proposed project will qualify RVax-1 for further characterization in preclinical and clinical evaluation.",,2025,University Of Texas Med Br Galveston,369885,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P21653,5R01AI150792-02,Live-attenuated Rift Valley fever vaccines: comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne zoonotic pathogen Rift Valley fever virus (RVFV). The consequences of this emerging virus could be exacerbated by insufficient vaccines for prevention of infection and disease. RVF is an important agroeconomic illness of domesticated livestock and is endemic in Africa and parts of the Middle East. Further spread is likely given that mosquito species capable of transmitting RVFV are found in Europe and the Americas. The most striking feature of RVF disease in sheep is a wave of fetal loss (known as an “abortion storm”) that sweeps through herds of pregnant animals, where spontaneous abortion rates can reach as high as 90%. Vaccination of livestock protects animals while simultaneously reducing the spread of RVFV to people. Obstacles in the successful development of RVFV livestock vaccines include: 1) vaccine strains often cause fetal infection and death in pregnant animals, and 2) vaccines that protect adult animals from disease are not always effective at preventing vertical transmission during pregnancy. These hurdles represent a major gap in the vaccine development field. The mechanisms by which live-attenuated vaccine strains of RVFV are vertically transmitted in utero, as well as the maternal immune response required for the protection of developing fetuses, are not known. No systematic evaluation of the vertical transmission potential of clinically- relevant live attenuated vaccines has been performed. To address this gap in the field, we propose to use an experimental rodent model of RVFV vertical transmission and fetal death in late-gestation pregnant rats. RVFV directly infects the placenta in rats, causes hemorrhage and inflammation, and results in fetal malformations including intrauterine fetal death even in pregnant dams without signs of disease. This proposal will use the pregnant rat model to test current RVF vaccine candidates for the mechanism(s) of vertical transmission, fetal protection, and identification of maternal immune correlates of fetal protection. We will also conduct a comparative analysis of virulent and attenuated RVFV strains for permissivity of placental explants from relevant species to identify cellular and structural targets of infection. Our overall hypothesis is that infection of pregnant rats with RVFV live-attenuated vaccines will provide pre-clinical quantitative data on vaccine safety for developing fetuses, efficacy for the fetuses, and critical maternal correlates of fetal protection. Completion of these studies will change the paradigm of RVFV vaccine development by providing, for the first time, a mechanistic explanation for the vertical transmission potential of clinically relevant LAVs.",,2026,University Of Pittsburgh At Pittsburgh,634557,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21654,1R21AI163603-01,Role of the novel entry factor Lrp1 in in vivo tropism and pathogenesis of Rift Valley fever virus,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne Rift Valley fever virus (RVFV). RVF is an important disease of domesticated livestock that is zoonotically transmitted to people, where it causes a spectrum of illness from mild to lethal. The significance of RVFV is highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of Priority Diseases, emphasizing the potential impact of RVFV on the global health and economy. Little is known about the entry factors that RVFV uses to infect cells from multiple species. Our rigorous and convincing preliminary data identify a cell surface receptor in the host lipid metabolism pathway that mediates infection of cells by RVFV. This proposal will determine the biological significance of this lipid receptor protein in RVFV disease in mice through conditional knockouts in cell types that are relevant to RVFV infection, including hepatocytes, neurons, and myeloid cells. We will use transient and genetic tissue-specific conditional gene knockouts of the lipid receptor generated using the Cre/Lox system. We hypothesize that eliminating lipid receptor expression in the liver will rescue mice from an otherwise highly lethal infection. We further hypothesize that conditional and tissue-specific gene deletions of the lipid receptor in mice will limit RVFV-associated pathogenic outcomes, including hepatic disease and encephalitis. Our highly collaborative and synergistic team is led by Dr. Amy Hartman (PI), an expert in the pathogenesis of RVFV, and by Dr. Gaya Amarasinghe (Co-I), a biochemist and biophysicist with expertise in host-pathogen interactions. This R21 proposal presents an opportunity to expand upon our collaborative efforts to determine the biological relevance of the RVFV-lipid receptor interaction in the mouse model. Completion of this proposal will have high impact on the field because it is the first in vivo assessment of receptor usage by RVFV. All reagents are available including mouse strains, viruses, and techniques; thus, the feasibility is high.",,2023,University Of Pittsburgh At Pittsburgh,246950,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21657,1R01AI150917-01,"Safety and immunogenicity of a novel Rift Valley fever candidate vaccine, RVax-1","Specific Aims Rift Valley fever (RVF), a mosquito-borne zoonotic viral disease affecting ruminants and humans endemic to sub-Saharan Africa, Egypt, Saudi Arabia and Yemen, is classified as Category A Priority Pathogen by the NIH/NIAID and the Blueprint priority disease by the World Health Organization. With One Health approach, a control of infected animals and mosquitoes are important to eradicate RVF from specific areas, whereas vaccinated humans will support overall activities including the handling of infected animals. There are, however, no licensed RVF vaccines for human use. Live-attenuated MP-12 vaccine, which was conditionally licensed in 2013 as a veterinary RVF vaccine in the U.S., had Investigational New Drug (IND) vaccine status, it has now been replaced with weakly immunogenic inactivated RVF candidate vaccine under IND. To develop a highly immunogenic and safe RVF candidate vaccine for human use, we have generated a novel live-attenuated candidate vaccine for RVF, termed “RVax-1”, which encodes more than 500 silent mutations throughout the open reading frame and a truncation of 78kD/NSm genes. Our central hypothesis is that the RVax-1 candidate vaccine is highly immunogenic in mice and marmosets via the intramuscular route with a single dose, highly attenuated in pregnant rat placenta and in infant mice, and disseminate poorly in mosquito vectors. The overall objective is characterize the immunogenicity, safety, and efficacy of the RVax-1 candidate vaccine in mice, rats, and marmosets, and to determine the level of viral dissemination in mosquitoes, in order to fill the gaps in knowledge regarding this candidate vaccine and move forward into IND-enabling preclinical and, subsequently, clinical evaluation. The work environment is ideal because the high containment facilities at the University of Texas Medical Branch are suitable for animal experiments, and SUNY Upstate Medical University supports mosquito experiments. The long-term goal of our study is to move the RVax-1 vaccine forward into preclinical evaluation, production under Good Manufacturing Practice, and Phase 1/2 trials. Specific Aim 1: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a mouse model. Specific Aim 2: To characterize the mosquito dissemination of RVax-1. Specific Aim 3: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a marmoset model. Specific Aim 4: To characterize the attenuation of RVax-1 in rat placenta. Successful completion of proposed project will qualify RVax-1 for further characterization in preclinical and clinical evaluation.",,2025,University Of Texas Med Br Galveston,402795,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Vector control strategies,2020 +P21658,1R01AI150792-01,Live-attenuated Rift Valley fever vaccines: comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses,"PROJECT SUMMARY/ABSTRACT The World Health Organization warns of a pending public health emergency caused by mosquito-borne zoonotic pathogen Rift Valley fever virus (RVFV). The consequences of this emerging virus could be exacerbated by insufficient vaccines for prevention of infection and disease. RVF is an important agroeconomic illness of domesticated livestock and is endemic in Africa and parts of the Middle East. Further spread is likely given that mosquito species capable of transmitting RVFV are found in Europe and the Americas. The most striking feature of RVF disease in sheep is a wave of fetal loss (known as an “abortion storm”) that sweeps through herds of pregnant animals, where spontaneous abortion rates can reach as high as 90%. Vaccination of livestock protects animals while simultaneously reducing the spread of RVFV to people. Obstacles in the successful development of RVFV livestock vaccines include: 1) vaccine strains often cause fetal infection and death in pregnant animals, and 2) vaccines that protect adult animals from disease are not always effective at preventing vertical transmission during pregnancy. These hurdles represent a major gap in the vaccine development field. The mechanisms by which live-attenuated vaccine strains of RVFV are vertically transmitted in utero, as well as the maternal immune response required for the protection of developing fetuses, are not known. No systematic evaluation of the vertical transmission potential of clinically- relevant live attenuated vaccines has been performed. To address this gap in the field, we propose to use an experimental rodent model of RVFV vertical transmission and fetal death in late-gestation pregnant rats. RVFV directly infects the placenta in rats, causes hemorrhage and inflammation, and results in fetal malformations including intrauterine fetal death even in pregnant dams without signs of disease. This proposal will use the pregnant rat model to test current RVF vaccine candidates for the mechanism(s) of vertical transmission, fetal protection, and identification of maternal immune correlates of fetal protection. We will also conduct a comparative analysis of virulent and attenuated RVFV strains for permissivity of placental explants from relevant species to identify cellular and structural targets of infection. Our overall hypothesis is that infection of pregnant rats with RVFV live-attenuated vaccines will provide pre-clinical quantitative data on vaccine safety for developing fetuses, efficacy for the fetuses, and critical maternal correlates of fetal protection. Completion of these studies will change the paradigm of RVFV vaccine development by providing, for the first time, a mechanistic explanation for the vertical transmission potential of clinically relevant LAVs.",,2025,University Of Pittsburgh At Pittsburgh,677858,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21660,5F30AI174686-02,Determining Tropism and Mechanisms of Ebola Virus Entry in Placental Tissues,"Project Summary/Abstract During pregnancy, viral infections in the mother may have catastrophic effects on her health, or on the viability of the developing fetus. Recently, emerging pathogen outbreaks such as those involving Zika Virus (ZIKV), SARS-CoV-2 or Ebola Virus (EBOV) have highlighted how understudied the role of the placenta is in transmission of viral infections. This project specifically focuses on the cell tropism of EBOV during pregnancy. Ebola Virus Disease (EVD) is caused by infection with EBOV or other members within the Ebolavirus genus. During pregnancy, EVD results in loss of ~100% of fetuses or neonates with or without the additional loss of the mother. Anecdotal data from EBOV outbreaks in Africa suggest that EBOV directly infects placental tissues, thus transmitting virus to the fetal compartment, but rigorous experimental evaluation of placental infection has not been performed; the tropism of EBOV for placental cells, mechanisms of cellular entry, and route of infection from mother to fetus are currently unknown. Aim 1 will examine tropism of EBOV in placental tissues. Further, as EBOV has been shown to bind to and internalize into many cell types via interactions with phosphatidylserine (PS) receptors, Aim 2 studies will evaluate the role of three PS receptors on EBOV infection of the placenta and fetus. These studies will be performed using two low containment EBOV model viruses, rVSV-EBOV-GP-GFP and EBOV ÃŽÂ""VP30, that have been used extensively to understand filovirus tropism and receptor usage. The knowledge gained from these rigorously designed studies will elucidate cell populations within the placenta infected and important for fetal transmission as a first step toward understanding the catastrophic pathogenesis of EVD in pregnancy. Additionally, this work will provide insights for the development of therapeutic treatment options to improve the maternal and fetal outcomes of EVD. The experiences, techniques, mentoring, and concepts in this proposal were specifically tailored to Ms. Hanora Van Ert and her training goals. As a developing researcher passionate about improving the health and wellbeing of pregnant women, Ms. Van Ert is currently completing her studies in the MSTP at University of Iowa under the scientific mentorship of Dr. Wendy Maury and Dr. Mark Santillan receiving individualized training at the intersection of virology, immunology, and reproductive health sciences to supply her passion with the necessary research skills. Additionally, the MSTP, Department of OB/Gyn, and Department of Microbiology and Immunology at the University of Iowa provide ample training opportunities in the forms of seminar series, funding for attending academic conferences, opportunities to meet prominent people in the fields of virology, immunology, and OB/Gyn, as well as a supportive and collaborative research environment. Ms. Van Ert will complete her MSTP training and pursue a research residency in OB/Gyn, clinical Maternal- fetal medicine fellowship, and ultimately tenure track position at an academic medical center to continue investigating the host-pathogen immune response at the maternal-fetal interface within the placenta.",,2025,University Of Iowa,39324,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21661,5R01AI174645-02,Dynamics and mechanisms of filovirus envelop glycoproteins,"SUMMARY The increasing frequency and severity of Ebola outbreaks demands an expanded repertoire of treatments and preventative measures. Answering this unmet need will require a deeper understanding of the molecular mechanisms underlying filovirus replication. In particular, the dynamic events that occur during filovirus envelope glycoprotein (GP)-mediated membrane fusion during entry into cells have evaded elucidation for decades. Previous studies have identified proteolytic cleavage of GP, receptor binding, and the chemical environment of the late endosome as being critical. But the molecular mechanisms by which these events and variables promote GP-mediated membrane fusion are not known. As a result, a complete and specific model of filovirus fusion, which integrates host factors, environmental conditions, and GP conformational changes currently does not exist. Therefore, filovirus entry continues to be an unutilized target for inhibitors. Our long-term goal is to develop a complete mechanistic model of GP-mediated membrane fusion. Our recent publications, in which we demonstrate the power of single-molecule fluorescence methods in elucidating the conformational dynamics of EBOV GP on the surface of virions, demonstrate our initial efforts toward this end. Here we aim to build on this success by proposing a multidisciplinary study involving virological, cellular, structural, and biophysical methodologies to elucidate the dynamics and mechanisms of GPs from multiple filoviruses. We will characterize the mechanisms by which conformational changes, host factors, and environmental variables facilitate filovirus membrane fusion and entry into cells. Completion of the proposed research will provide mechanistic insights into filovirus entry and the viral and host targets that could be exploited with novel therapies and immunogens.",,2027,UNIV OF MASSACHUSETTS MED SCH WORCESTER,782818,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21662,5UH2AI169710-02,Elucidating mechanisms of interferon gamma that protect against Ebola virus infection,"Abstract Filovirus outbreaks/epidemics occur sporadically, but with increasing frequency and intensity. With no current approved filovirus therapeutics, the recent Ebola virus (EBOV) outbreaks emphasize the need for effective treatments against this highly pathogenic family of viruses. A better mechanistic understanding of effective early immune responses to EBOV will identify potential immunological approaches for controlling this infection and associated disease. Interferon gamma (IFN-γ) elicits production of antiviral proteins that control of virus replication and stimulates and activates cellular immune responses. In a series of recent studies, we demonstrated that IFN-γ profoundly inhibits EBOV infection of macrophages, an important early cellular target for the virus. We also showed that IFN-γ protects mice from EBOV challenge when mice were treated 24 hours prior to or after infection. These findings provide evidence that the immune responses elicited following IFN-γ stimulation effectively control EBOV infection and disease. Here, we will explore the contribution of both innate and cellular immunity to IFN-γ- mediated protection. In total, studies proposed here will provide critical mechanistic insights into the efficacy of this immune pathway to control filovirus infections.",,2024,University Of Iowa,193125,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2022 +P21663,75N93023C00001-0-9999-1,DEVELOPMENT OF PAN-FILOVIRUS THERAPEUTICS,"To support the advanced development of a promising candidate therapeutic for a virus under the Antiviral Program for Pandemics. The research and development activities to be supported will allow the candidate therapeutic product to progress through the product development pathway, and include preclinical and IND enabling development activities, chemistry optimization/development, GMP manufacturing, and clinical safety and efficacy assessment.",,2023,"MICROBIOTIX, INC",2069416,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies,2022 +P21664,5R44AI150263-04,A modular platform for infectious disease surveillance at point-of-need.,"ABSTRACT We propose to develop a point-of-need system for differential molecular identification of filoviruses from syndromically similar infections. Our goal is to enable rapid, sensitive, and specific identification of quarantinable infections to reduce nosocomial risk and improve outbreak response. The platform will simultaneously test 12 genomic markers at the genus and strain level using a modular microfluidic design that allows for rapid panel update and expansion. In Phase I we will develop an assay for pan-filovirus (pFi), followed by expansion of the panel and system integration in Phase II. The expanded panel will add pan-flavivirus (pFa) and pan-Plasmodium (pPa) detection as well as strain-specific targets for Ebola, Marburg, Dengue, Yellow Fever, and Malaria. Strain specific tests will enable better patient triage/treatment during an outbreak and improve disease surveillance in non-outbreak settings. The panel will require a 50 μL sample of whole blood and will achieve highly specific detection in < 30 minutes. To achieve this goal, we will combine Redbud Labs’ expertise in microfluidics and systems with the diagnostic development expertise of the Diagnostics Program at PATH (Seattle, WA), and the VHF testing/processing capabilities of the Connor Lab at Boston University (part of the BSL-4 facilities at NEIDL).",,2024,"REDBUD LABS, INC.",983642,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21665,5R21AI169646-02,Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo,"ABSTRACT Bats play an important role as natural reservoirs of numerous RNA viruses with the potential to cause significant harm to humans. In this proposal, we focus on Lloviu virus (LLOV), an under-investigated filovirus that circulates in Schreiber’s bats (Miniopterus schreibersii) in Europe. Although the pathogenic potential of LLOV for humans is not known, the close relationship of LLOV to the highly pathogenic Ebola and Marburg viruses raises concerns that a potential spillover event could lead to an outbreak among humans. LLOV was first detected Schreiber’s bats in Spain in 2002 and then again in Hungary in 2016. Sequence comparison of the Spanish and the Hungarian LLOV RNA genomes suggests that RNA editing by cellular deaminases, such as ADAR and APOBEC, might play a role in LLOV sequence diversification. In this application, we propose to explore if host-mediated RNA editing drives LLOV sequence divergence and evolution in Schreiber’s bats. In Aim 1, we propose to sample Schreiber’s bats from geographically distinct colonies and obtain LLOV sequence information from infected bats for comparative analysis. We will further develop tools based on highly sensitive droplet RT-PCR and RNA FISH that allow to determine the expression pattern of ADARs and APOBECs in LLOV-infected bat cell culture and in blood samples from infected animals. In Aim 2, based on the determined ADAR and APOBEC expression patterns, we will knockout select ADAR and/or APOBEC genes that might be involved in LLOV RNA editing in the bat cell line and examine the role of these genes in LLOV sequence diversification and viral fitness in serial passaging experiments and cell culture infection studies. Upon completion of this work, we will have revealed whether host-specific RNA editors are the drivers of LLOV evolution in bat cells. This work will contribute to our understanding of host-driven viral sequence divergence and might help assess the risk of potential LLOV spillover events from bats to humans through host-driven changes in viral sequences.",,2024,Boston University Medical Campus,186300,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Vector biology",2022 +P21666,5R01AI156866-05,Spillover of Ebola and other filoviruses at ecological boundaries,"More than half of all infectious disease outbreaks across the globe are zoonotic, involving pathogen spillover from animal reservoirs to humans. Ebola and other filoviruses rank among the most deadly zoonoses. Recent large outbreaks with mortality in the thousands both in humans and wildlife underscore the pressing need to better understand the factors promoting filovirus spillover. Although spillover is commonly defined as a pathogen crossing species boundaries, there are relatively few empirical studies or modeling frameworks that explicitly consider ecological boundaries across which spillover occurs. Crossing ecological boundaries involves processes that occur at many levels of organization: physiological processes at the individual level, interspecies interactions between individuals at the population level, interactions between populations of different species at the community level, and interactions between ecological communities within landscapes. Processes accelerating spillover often involve human activities such as habitat encroachment and land conversion, which are themselves ultimately driven by socioeconomic factors. In the context of Ebola and other filoviruses in Africa, we will develop the data sets, theoretical models and statistical tools needed for a general descriptive and predictive framework for spillover at ecological boundaries. Our project will follow an iterative design where results from mechanistic models are used to refine patterns that we test for empirically, and statistical models of large-scale data allow us to more realistically parameterize mechanistic models. Our work will test the generality of specific theories that so far have been applied only to a limited number of study systems. For example, ours will be among the first attempts to test the influence of Schmalhausen’s law -- an evolutionary theory that may explain the tendency for large outbreaks to occur at the edges of species ranges or during unusual weather conditions and which to date has primarily been investigated in the context of malaria -- in pathogens that rely on direct transmission. This work will demonstrate how new methods can provide unifying insight into patterns in critically important disease transmission systems and will enhance our ability to predict spillover of both filoviruses and many other zoonotic pathogens. Note that no human subjects, biohazards, or select agents will be involved in this project.",,2025,Oklahoma State University Stillwater,420321,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21667,1F30AI174686-01,Determining Tropism and Mechanisms of Ebola Virus Entry in Placental Tissues,"Project Summary/Abstract During pregnancy, viral infections in the mother may have catastrophic effects on her health, or on the viability of the developing fetus. Recently, emerging pathogen outbreaks such as those involving Zika Virus (ZIKV), SARS-CoV-2 or Ebola Virus (EBOV) have highlighted how understudied the role of the placenta is in transmission of viral infections. This project specifically focuses on the cell tropism of EBOV during pregnancy. Ebola Virus Disease (EVD) is caused by infection with EBOV or other members within the Ebolavirus genus. During pregnancy, EVD results in loss of ~100% of fetuses or neonates with or without the additional loss of the mother. Anecdotal data from EBOV outbreaks in Africa suggest that EBOV directly infects placental tissues, thus transmitting virus to the fetal compartment, but rigorous experimental evaluation of placental infection has not been performed; the tropism of EBOV for placental cells, mechanisms of cellular entry, and route of infection from mother to fetus are currently unknown. Aim 1 will examine tropism of EBOV in placental tissues. Further, as EBOV has been shown to bind to and internalize into many cell types via interactions with phosphatidylserine (PS) receptors, Aim 2 studies will evaluate the role of three PS receptors on EBOV infection of the placenta and fetus. These studies will be performed using two low containment EBOV model viruses, rVSV-EBOV-GP-GFP and EBOV ÃŽÂ""VP30, that have been used extensively to understand filovirus tropism and receptor usage. The knowledge gained from these rigorously designed studies will elucidate cell populations within the placenta infected and important for fetal transmission as a first step toward understanding the catastrophic pathogenesis of EVD in pregnancy. Additionally, this work will provide insights for the development of therapeutic treatment options to improve the maternal and fetal outcomes of EVD. The experiences, techniques, mentoring, and concepts in this proposal were specifically tailored to Ms. Hanora Van Ert and her training goals. As a developing researcher passionate about improving the health and wellbeing of pregnant women, Ms. Van Ert is currently completing her studies in the MSTP at University of Iowa under the scientific mentorship of Dr. Wendy Maury and Dr. Mark Santillan receiving individualized training at the intersection of virology, immunology, and reproductive health sciences to supply her passion with the necessary research skills. Additionally, the MSTP, Department of OB/Gyn, and Department of Microbiology and Immunology at the University of Iowa provide ample training opportunities in the forms of seminar series, funding for attending academic conferences, opportunities to meet prominent people in the fields of virology, immunology, and OB/Gyn, as well as a supportive and collaborative research environment. Ms. Van Ert will complete her MSTP training and pursue a research residency in OB/Gyn, clinical Maternal- fetal medicine fellowship, and ultimately tenure track position at an academic medical center to continue investigating the host-pathogen immune response at the maternal-fetal interface within the placenta.",,2025,UNIVERSITY OF IOWA,38960,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21668,5U01AI160397-03,"Defining molecular mechanisms of combination adjuvants: a systems immunology, transcriptomics and imaging approach","PROJECT SUMMARY/ABSTRACT In this proposal we will define molecular and cellular mechanisms of different combinations of known adjuvant components MPLA (a TL4 agonist), CpG (a TLR9 agonist), agonists of cGAS-STING and NOD1/2 pathways, and a squalene-in-water emulsion (AddaVAXâÂ""¢). Our overall Aim is to provide a detailed analysis of every combination of these using high throughput in vitro and in vivo assays, followed an in-depth analysis of two combination adjuvants using live cell imaging and single-cell mRNA sequencing of draining lymph nodes after vaccination. Initially, 96-well based in vitro assays of innate and adaptive immune system activation will be used to profile different adjuvants components, both individually, and in different combinations and concentrations. These assays will comprise: 1) activation of TLR, NOD and STING signaling pathways using primary dendritic cells (DCs), T and B cells from reporter transgenic mice; 2) in vitro activation of naïve B cells to monitor their differentiation into plasma cells and class switching. We anticipate some of the adjuvant combinations will have synergistic effects that differ from the sum of the effects when used individually. Next, based on performance in vitro a subset of combination adjuvants and their individual components will be evaluated as adjuvants for model vaccine antigens (influenza hemagglutinin H1, filovirus (EBOV) glycoprotein and SARS-CoV-2 spike) in vivo in mice. Immunogenicity metrics will comprise: 1) antibody dynamics and durability, isotype, avidity and breadth of cross-reactivity using protein microarrays; 2) flow cytometry of antigen-specific B cells to assess differentiation and cross-reactivity; 3) T cell recall assays to define Th1/Th2/Th17 cytokine profiles; 4) neutralization by sera of live influenza, SARS-CoV-2 and VSV-pseudotyped with EBOV glycoprotein. This will provide a comprehensive cellular and molecular profile associated with each combination adjuvant. Two combination adjuvants (and their individual components for comparison) will be selected for a deep analysis using: 1) transgenic mice that allow Ca2+ fluxes in live CD4 T and B cells and DCs to be visualized using 2- photon microscopy. Combined with techniques of whole tissue imaging, we will monitor adjuvant-driven T cell and DC mobilization, motility and interactions in live draining lymph nodes; 2) using single-cell RNAseq technology (10x Genomics Inc) of cells in draining lymph nodes, we will define cell composition and phenotype, cellular interactions and spatial organization. We will perform a deep analysis in Year 1 on the combination adjuvant CpG/MPLA + AddaVAX (TLR9 and TLR4 agonists in a squalene-in-water emulsion) since we have already shown this is a powerful combination adjuvant. A second combination adjuvant will be selected for deep analysis based on data generated in the in vitro and in vivo assays described herein. Together these complementary deep approaches will provide an unprecedented level of molecular and cellular detail of two highly effective combination adjuvants. Overall, we anticipate these data will help guide the future design of vaccines where the immune response required can be tuned according to the particular pathogen in question.",,2025,University Of California-Irvine,592289,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Orthomyxoviridae,H1,Unspecified,,,,,,,COVID-19 | Ebola virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21669,75N93020C00040-P00007-9999-1,Advanced Development of Vaccines for Filoviruses ,"To support the advanced development of multivalent vaccine candidates for filoviruses and Lassa Fever. This contract aims to formulate a multivalent vaccine that provides protection against several pathogens, including Ebola virus, Marburg virus and Lassa Fever. It may support cGMP manufacture of a stable lyophilized vaccine formulation and preparation and submission of an IND to support eventual clinical evaluation.",,2026,AURO VACCINES LLC,4095421,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P21670,272201700040I-P00003-759302200002-1,Task A66: Rodent models for testing therapeutics against filoviruses,"This contract provides for the development and standardization of small animal models of infectious diseases, and may include efficacy testing of candidate products, including GLP studies to support licensure.",,2023,University Of Texas Med Br Galveston,335518,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2022 +P21672,5U01AI151814-04,EpiCenter for Emerging Infectious Disease Intelligence,"Project Summary/Abstract: The Epicenter for Emerging Infectious Disease Intelligence brings together a consortium of leading research institutions to advance an understanding of viral emergence from wildlife into humans living in forest and rapidly urbanizing ecosystems. Our work will enhance preparedness for disease emergence events in the Congo Basin and Amazon Basin forest regions and facilitate response efforts at the source of emergence. Our multidisciplinary team has internationally recognized expertise in infectious disease epidemiology, virology, human health, animal health, medical entomology, microbiology, and disease modeling. Our proposed activities integrate human, animal, and vector surveillance to enable insight into cross-species disease transmission and facilitate responsiveness to evolving needs that impact country, regional, and global emerging infectious disease risk. In our initial work, we propose to investigate the epidemiology of arboviruses and filoviruses, which include emerging viruses currently threatening global health security. We will evaluate disease transmission dynamics at the primary stage of emergence in humans, in forest communities where people are highly susceptible to virus spillover from wildlife and mosquitos. We will also investigate these viruses in the second stage of emergence, in urban centers peripherally connected to forests, where viruses have adapted to human-to-human transmission (by direct or vector-borne transmission). Targeted filoviruses and arboviruses at proposed sites in Uganda and Peru represent a range of emergence histories, from recent emergence events, to seasonal and annual re- emergence events, to introduction events where viruses have adapted to entirely new ecosystems, vectors, and vertebrate hosts. Research at these sites will advance our understanding of cross-species transmission for viruses across this spectrum of emergence. Our work will optimize best practices in acute febrile illness surveillance in high-risk communities coupled with wildlife and entomologic risk characterization studies to facilitate deployment of next generation techniques in early detection of virus emergence and monitoring of sustained transmission in at-risk communities. Our consortium has a demonstrated commitment to strengthening international capabilities for emerging infectious disease research in resource-limited countries. We are well- poised to contribute to important advances in capacity in the Amazon and Congo Basin forest region with partners in Uganda and Peru for completion of our proposed project and long-term sustainability for the greater region and across the Emerging Infectious Disease Research Center network.",,2025,University Of California At Davis,1555321,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Disease transmission dynamics",2020 +P21673,3U01AI151814-04S1,EpiCenter for Emerging Infectious Disease Intelligence,"Project Summary/Abstract: The Epicenter for Emerging Infectious Disease Intelligence brings together a consortium of leading research institutions to advance an understanding of viral emergence from wildlife into humans living in forest and rapidly urbanizing ecosystems. Our work will enhance preparedness for disease emergence events in the Congo Basin and Amazon Basin forest regions and facilitate response efforts at the source of emergence. Our multidisciplinary team has internationally recognized expertise in infectious disease epidemiology, virology, human health, animal health, medical entomology, microbiology, and disease modeling. Our proposed activities integrate human, animal, and vector surveillance to enable insight into cross-species disease transmission and facilitate responsiveness to evolving needs that impact country, regional, and global emerging infectious disease risk. In our initial work, we propose to investigate the epidemiology of arboviruses and filoviruses, which include emerging viruses currently threatening global health security. We will evaluate disease transmission dynamics at the primary stage of emergence in humans, in forest communities where people are highly susceptible to virus spillover from wildlife and mosquitos. We will also investigate these viruses in the second stage of emergence, in urban centers peripherally connected to forests, where viruses have adapted to human-to-human transmission (by direct or vector-borne transmission). Targeted filoviruses and arboviruses at proposed sites in Uganda and Peru represent a range of emergence histories, from recent emergence events, to seasonal and annual re- emergence events, to introduction events where viruses have adapted to entirely new ecosystems, vectors, and vertebrate hosts. Research at these sites will advance our understanding of cross-species transmission for viruses across this spectrum of emergence. Our work will optimize best practices in acute febrile illness surveillance in high-risk communities coupled with wildlife and entomologic risk characterization studies to facilitate deployment of next generation techniques in early detection of virus emergence and monitoring of sustained transmission in at-risk communities. Our consortium has a demonstrated commitment to strengthening international capabilities for emerging infectious disease research in resource-limited countries. We are well- poised to contribute to important advances in capacity in the Amazon and Congo Basin forest region with partners in Uganda and Peru for completion of our proposed project and long-term sustainability for the greater region and across the Emerging Infectious Disease Research Center network.",,2025,University Of California At Davis,398937,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Disease transmission dynamics",2020 +P21674,5R01AI146172-05,Dissecting catalytic and regulatory functions of nonsegmented negative strandRNA viral polymerases,"Non-segmented negative strand (NNS) RNA viruses, such as rabies virus (RABV), human respiratory syncytial virus (HRSV), human parainfluenza virus type 3 (HPIV3), and Ebola virus (EBOV), pose continuing threats to human health, but there are currently no established prophylactic and/or therapeutic countermeasures against most NNS RNA viral diseases. NNS RNA viruses possess a multifunctional RNA-dependent RNA polymerase (RdRp) large (L) protein, which catalyzes all enzymatic reactions required for viral RNA biogenesis (e.g., RNA synthesis, 5′-capping, cap methylation at the guanine-N7- and ribose-2′-O-positions, 3′-polyadenylation). All these enzymatic activities of the L proteins are unique and potentially druggable. Our goals are to elucidate the molecular mechanisms of RNA synthesis and processing with the L proteins and to develop anti-viral agents against them. To dissect the roles of the L proteins in RNA biosynthesis, we have developed a number of in vitro rhabdoviral RNA synthesis and processing systems for prototypic vesicular stomatitis virus (VSV) and RABV. Using these systems, we discovered that rhabdoviral L proteins catalyze unconventional mRNA capping with a novel GDP polyribonucleotidyltransferase (PRNTase, EC 2.7.7.88) domain. However, the mechanisms of pre- mRNA capping and methylation coupled to mRNA chain elongation remain largely unknown. Furthermore, virus- specific functions of L proteins have not been studied. We hypothesize that L proteins catalyze common enzymatic reactions via evolutionary conserved elements, but manifest virus-specific functions via diversified elements. This hypothesis will be rigorously tested by the following specific aims: to elucidate the mechanisms of (1) co-transcriptional mRNA maturation by rhabdoviral L proteins, (2) cap formation by pneumoviral and paramyxoviral L proteins, and (3) transcription and replication by filoviral L proteins. In Aim 1, we will determine the timing and order of pre-mRNA processing by the VSV L protein during mRNA chain elongation, leading to a new model of co-transcriptional mRNA maturation by L proteins of rhabdoviruses and, by extension, other NNS RNA viruses. In Aim 2, we will reveal common and diversified functions of putative PRNTase and methyltransferase domains of the HRSV and HPIV3 L proteins in mRNA cap formation. In Aim 3, we will provide a novel model for genome replication by the EBOV L protein that is significantly different from that by other NNS RNA viral L proteins. Collectively, the proposed studies will open up a new frontier in understanding how diversified NNS L proteins carry out each step of RNA synthesis and processing together with their cognate co- factor proteins. Our studies will provide foundations for the future development of antiviral agents targeting unique L domains of these significant NNS RNA viruses.",,2024,University Of Toledo Health Sci Campus,347625,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P21675,5R01AI151144-03,Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.,"ABSTRACT This project focuses on understanding the role that the unique physiology of bats plays in their ability to act as host reservoirs for diseases that can spill over to humans. The project will be carried out under field conditions in Uganda on three species of bats that have varying links to the spread of Ebola virus (EBOV) to humans. By comparing the ability of these three species of bats to respond to Ebola-like immune challenges, this work will help identify the characteristics that contribute to spillover risk. In the long term, this work will help identify host species for EBOV and other related viruses that present risk to humans. It will also help explain how different species of bats respond to different types of viral infections. The main focus of this project will be to identify behaviors and molecular pathways that enable reservoir hosts to tolerate infections, providing critical insight into one of the mechanisms that leads to spillover. This work is driven by the hypothesis that some bat species have coevolved with particular types of viral infections and, therefore, have adapted mechanisms to minimize pathology during infection. Bats are globally biodiverse and have many unique ecological and physiological adaptations, including flight and the ability to employ both hypo- and hyperthermic body temperature regulation. This project focuses on three bat species chosen because they are in close contact with humans, their habitats cover the range of EBOV exposure risk, and they have divergent coevolutionary histories with viral pathogens; two of the three species have significant ties to EBOV epidemiology. This project addresses these questions under natural conditions in the field by taking the innovative approach of using EBOV virus-like particles as a proxy for experimental infection with biohazardous pathogens. This project has three specific aims that will allow the achievement of its goals. First, the project tests the hypothesis that specific African bat species will display signatures of EBOV disease tolerance in response to challenge with EBOV virus-like particles, and thus are likely to be natural reservoir hosts. These experiments will provide significant insight into disease tolerance in bats and the potential identity of EBOV reservoir(s). Second, this project tests the hypothesis that bats display variable levels of disease tolerance that depend upon innate immune pathways that have undergone unique evolutionary selection in bats. Third, this project explores whether tolerance of and resistance to viral infection are facilitated by the unique metabolic behaviors of bats, namely that they can depress metabolism and enter torpor to conserve energy and can elevate metabolism and thus temperature during flight. The role of changes in body temperature is poorly understood and these experiments will identify whether these physiological responses contribute to immunological tolerance and resistance in important disease reservoirs. Together, the successful completion of these goals will help determine whether infection tolerance confers on African bat species the ability to serve as reservoir hosts for virulent zoonotic viruses and will identify molecular, physiological, and behavioral mechanisms that contribute to tolerance phenotypes.",,2026,Bucknell University,614037,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +P21677,1UH2AI174415-01A1,Defining the effect of Plasmodium infection on Ebola virus vaccine efficacy,"PROJECT SUMMARY Zaire Ebola virus (EBOV) infections remain an emerging threat in Central and West Africa with case fatality rates reaching as high as 90%. An FDA-approved, live-attenuated, recombinant vaccine called ERVEBO has shown promise during recent outbreaks in Guinea in 2016 and Democratic Republic of the Congo (DRC) in 2019. ERVEBO stimulates antibody responses directed against the EBOV glycoprotein (GP). “Ring vaccination” is the current emergency immunization strategy that focuses on immunizing direct contacts and geographically proximal populations surrounding the epicenter of an EBOV outbreak. However, emerging data in the DRC show that ring vaccination can be highly porous; nearly 30% of EBOV-infected participants in a recent antiviral trial in the DRC were prior recipients of the ERVEBO vaccine. The mechanistic bases for these vaccine failures are not known. This multi-PI, interdisciplinary project explores the hypothesis that acute malaria impairs EBOV immunization-induced B and T cell responses. In support of this hypothesis, EBOV outbreaks largely occur where Plasmodium falciparum infections are endemic; malaria is common throughout Central and West Africa. Moreover, our collaborative team has developed experimental Plasmodium infection and EBOV vaccination systems to generate preliminary data showing that malaria dramatically impairs EBOV vaccine-induced, virus- specific antibody responses. We have also identified potential strategies to overcome the malaria-associated impairments in vaccine efficacy. In this project we synergistically apply tractable, high-resolution, antigen-specific systems to determine the mechanisms by which Plasmodium infections impact EBOV vaccine-induced humoral and cellular immunity. These new approaches facilitate our long-term goal to define the impact of Plasmodium infection on the efficacy of EBOV vaccine-induced immune responses. Our goal is addressed by three specific aims that test: 1) how Plasmodium infections impact vaccine-induced, virus specific B cell responses; 2) how Plasmodium infections influence the function of helper T cell subsets required for promoting antibody responses; and 3) how malaria affects EBOV vaccine-induced protection against virulent mouse adapted, BSL-4 EBOV challenge. Successful completion of these studies will reveal the mechanisms by which Plasmodium infections impair EBOV vaccine responses and provide clinically applicable approaches to overcome this impairment. Such knowledge gained will inform vaccine strategies that must be rapidly and effectively implemented during EBOV outbreaks.",,2025,University Of Iowa,233250,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Characterisation of vaccine-induced immunity,2023 +P21678,1R21AI169558-01A1,Using Bacterial Effectors to Uncover Innate Immune Mechanisms Restricting Viral Replication in Bat Cells,"ProjectÃ' SummaryÃ'  Ã'  BatsÃ' areÃ' importantÃ' reservoirsÃ' forÃ' diverseÃ' viralÃ' pathogensÃ' affectingÃ' humans.Ã' However,Ã' weÃ' haveÃ' aÃ' poorÃ'  understandingÃ'  ofÃ' theÃ'  keyÃ' batÃ'  innateÃ'  immunityÃ' factorsÃ'  thatÃ'  restrictÃ'  virusÃ'  replication.Ã'  FunctionalÃ'  assaysÃ'  thatÃ'  canÃ'  identifyÃ'  batÃ'  factorsÃ'  thatÃ'  areÃ'  trulyÃ'  relevantÃ'  toÃ'  combatingÃ'  virusesÃ'  areÃ'  neededÃ'  toÃ'  understandÃ'  theÃ'  innateÃ'  immuneÃ'  mechanismsÃ' thatÃ' ultimatelyÃ' defineÃ' batÃ' susceptibilityÃ' toÃ' viralÃ' infection.Ã' WhileÃ' historicallyÃ' suchÃ' functionalÃ' screensÃ'  haveÃ'  reliedÃ'  onÃ'  genome-Ã'­wideÃ'  genomicÃ'  editingÃ'  (e.g.Ã'  CRISPR-Ã'­Cas9)-Ã'­Ã'  orÃ'  RNAÃ'  interferenceÃ'  (RNAi)-Ã'­basedÃ'  techniques,Ã' suchÃ' platformsÃ' areÃ' unavailableÃ' forÃ' mostÃ' batÃ' species.Ã' Thus,Ã' newÃ' methodsÃ' forÃ' uncoveringÃ' functionally-Ã'­ relevantÃ' componentsÃ' ofÃ' theÃ' batÃ' immuneÃ' responseÃ' toÃ' virusÃ' infectionÃ' areÃ' needed.Ã' ToÃ' addressÃ' thisÃ' need,Ã' weÃ' haveÃ'  developedÃ'  anÃ'  innovativeÃ'  arbovirusÃ'  ""rescue""Ã'  assayÃ'  whereinÃ'  immuneÃ'  evasionÃ'  proteinsÃ'  (IEPs)Ã'  encodedÃ'  byÃ'  mammalianÃ' pathogensÃ' canÃ' beÃ' expressedÃ' inÃ' batÃ' cellsÃ' andÃ' oneÃ' canÃ' assayÃ' forÃ' changesÃ' inÃ' batÃ' cellÃ' susceptibilityÃ' toÃ'  arbovirusÃ' infection.Ã' EnhancementÃ' ofÃ' arbovirusÃ' replicationÃ' afterÃ' expressionÃ' ofÃ' aÃ' candidateÃ' IEPÃ' indicatesÃ' thatÃ' theÃ'  IEPÃ'  likelyÃ'  inhibitsÃ'  batÃ'  immunityÃ'  mechanismsÃ'  thatÃ'  normallyÃ'  restrictÃ'  arbovirusÃ'  replication.Ã'  UsingÃ'  theseÃ'  IEPsÃ'  asÃ'  ""tools"",Ã'  oneÃ'  canÃ'  thenÃ'  identifyÃ'  theÃ'  batÃ'  immunityÃ'  factorsÃ'  theseÃ'  IEPsÃ'  target.Ã'  Thus,Ã'  thisÃ'  screeningÃ'  methodologyÃ'  providesÃ'  aÃ'  mechanismÃ'  toÃ'  bothÃ'  identifyÃ'  novelÃ'  IEPsÃ'  andÃ'  functionally-Ã'­relevantÃ'  componentsÃ'  ofÃ'  theÃ'  batÃ'  immuneÃ'  response.Ã' ToÃ' discoverÃ' IEPsÃ' thatÃ' promoteÃ' arbovirusÃ' replicationÃ' inÃ' batÃ' cells,Ã' weÃ' willÃ' screenÃ' anÃ' expressionÃ' libraryÃ'  encodingÃ' ~200Ã' bacterialÃ' effectorÃ' proteins.Ã' BacterialÃ' effectorsÃ' areÃ' proteinsÃ' secretedÃ' byÃ' pathogenicÃ' bacteriaÃ' intoÃ'  eukaryoticÃ'  hostsÃ'  cellsÃ'  thatÃ'  modulateÃ'  orÃ'  inhibitÃ'  variousÃ'  eukaryoticÃ'  cellularÃ'  processesÃ'  toÃ'  promoteÃ'  bacterialÃ'  replication.Ã'  ManyÃ'  bacterialÃ'  pathogensÃ'  thatÃ'  replicateÃ'  inÃ' theÃ'  cytoplasmÃ'  ofÃ'  eukaryoticÃ'  hostÃ' cellsÃ'  encodeÃ'  effectorsÃ'  thatÃ' functionÃ' asÃ' IEPs.Ã' Thus,Ã' weÃ' hypothesizeÃ' thatÃ' someÃ' effectorsÃ' mayÃ' suppressÃ' immuneÃ' responsesÃ' thatÃ' restrictÃ'  bothÃ'  bacteriaÃ'  andÃ'  cytoplasmicÃ'  virusesÃ'  suchÃ'  asÃ'  arboviruses.Ã'  Indeed,Ã'  ourÃ'  initialÃ'  screensÃ'  haveÃ'  identifiedÃ'  fourÃ'  effectorsÃ'  thatÃ'  promoteÃ'  theÃ'  replicationÃ'  ofÃ'  fourÃ'  differentÃ'  arbovirusesÃ'  whenÃ'  expressedÃ'  inÃ'  batÃ'  cells.Ã'  WeÃ'  haveÃ'  characterizedÃ' oneÃ' ofÃ' theseÃ' effectorÃ' screenÃ' ""hits""Ã' asÃ' aÃ' novelÃ' ubiquitinÃ' ligaseÃ' thatÃ' targetsÃ' anÃ' uncharacterizedÃ' RingÃ'  FingerÃ' (RNF)Ã' Domain-Ã'­containingÃ' proteinÃ' forÃ' degradationÃ' inÃ' eukaryoticÃ' cells.Ã' Importantly,Ã' RNAiÃ' depletionÃ' ofÃ' thisÃ'  RNFÃ' factorÃ' inÃ' humanÃ' andÃ' batÃ' cellsÃ' promotesÃ' arbovirusÃ' replication,Ã' suggestingÃ' thatÃ' itÃ' mayÃ' beÃ' aÃ' novelÃ' componentÃ'  ofÃ' humanÃ' andÃ' batÃ' immuneÃ' responses.Ã' TheseÃ' resultsÃ' suggestÃ' thatÃ' weÃ' canÃ' useÃ' bacterialÃ' effectorsÃ' asÃ' toolsÃ' toÃ' bothÃ'  inhibit,Ã' andÃ' identify,Ã' functionally-Ã'­relevantÃ' immunityÃ' factorsÃ' inÃ' bats.Ã' OurÃ' studyÃ' hasÃ' theÃ' followingÃ' specificÃ' aims:Ã' 1)Ã'  IdentifyÃ'  bacterialÃ'  effectorÃ'  proteinsÃ'  thatÃ'  promoteÃ'  arbovirusÃ'  replicationÃ'  inÃ'  batÃ'  cells;;Ã'  2)Ã'  IdentifyÃ'  batÃ'  proteinsÃ'  interactingÃ'  withÃ'  effectorÃ'  “hits”Ã'  fromÃ'  ourÃ'  arbovirusÃ'  rescueÃ'  assays;;Ã'  andÃ'  3)Ã'  DetermineÃ'  whichÃ'  batÃ'  hostÃ'  factorsÃ'  interactingÃ'  withÃ'  effectorÃ'  proteinÃ'  hitsÃ'  affectÃ'  viralÃ'  replication.Ã'  OurÃ'  long-Ã'­termÃ'  goalÃ'  isÃ'  toÃ'  useÃ'  thisÃ'  modelÃ'  systemÃ'  toÃ'  defineÃ' theÃ' keyÃ' batÃ' innateÃ' immuneÃ' mechanismsÃ' thatÃ' restrictÃ' arbovirusÃ' replication.Ã' Ã'  Ã'  Ã'  Ã'  Ã' ",,2025,UT SOUTHWESTERN MEDICAL CENTER,246000,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Filoviridae | Other,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2023 +P21679,1R01AI175698-01,The Protective and Pathologic Features of the EVD Survivor Immune System,"In the more than 40 years since the discovery of the Ebola virus (EBOV) there has been an increase in both the frequency, size, and duration of Ebola outbreaks. The 2014-2016 outbreak that devastated West Africa evolved within the span of months into a global humanitarian crisis, infecting over 28,600 people and killing more than 11,300 - eclipsing all previous outbreaks combined. Moreover, in the six years since the end of the West African Ebola epidemic, there have been seven additional outbreaks in Guinea and the Democratic Republic of Congo (DRC). The recurrence of Ebola in Guinea and the DRC and the detection of the Ebola virus in a bat in Liberia, make it clear that this pathogen is persistent and will be the cause of recurrent outbreaks of varying scales across West and Central Africa. While the West African epidemic has ended, the clinical concerns of EVD survivors persist including the longevity of immune protection against repeat infection and the mechanisms underlying the persistent and debilitating somatic complaints reported by an overwhelming majority. The primary objective of this proposal is a rigorous characterization of the protective and pathologic effects of the EVD survivor immune response in one of the largest EVD survivor cohorts. Specifically: • AIM I will characterize the humoral immune response to EBOV infection by measuring antibody levels and neutralizing capacity - a key correlate of protection, and assessing the memory immune response in seronegative EVD survivors from 1 to 10 years following acute infection • AIM II will investigate autoimmune activation as a mechanism underlying post-Ebola complications We will conduct this work in the context of close and strong working relationships with healthcare leaders and Ebola survivor representatives in West Africa, and well-developed infrastructure for clinical research that we have established in Liberia and Sierra Leone where we have recruited, enrolled, and longitudinally followed and sampled more than 700 EVD survivors and over 1,000 household contacts. The proposed work will provide a much-needed longitudinal characterization of the humoral immune response, evaluation of the memory immune response to EBOV infection, and investigation of autoimmune activation as a mechanism underlying the long- term complications of surviving EVD. With seven outbreaks, including the second largest Ebola outbreak ever, occurring in the 6 years since the West African epidemic, the question is not if another large outbreak will occur but when. This study will ensure that the world is better prepared for the next epidemic through an improved understanding of the durability of the humoral immune response to infection, an improved understanding of the clinical complications of EVD, and through the implementation of clinical research platforms in areas that are likely to see a recurrence of EVD.",,2028,UNIV OF NORTH CAROLINA CHAPEL HILL,715921,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease surveillance & mapping | Post acute and long term health consequences,2023 +P21681,1R21AI178151-01,Large-scale compatibility assessments between ACE2 proteins and diverse sarbecovirus spikes,"PROJECT SUMMARY Viral spillover from animal reservoirs into humans can decimate public health systems and cripple the world economy, as evident with the current SARS-CoV-2 pandemic. Continued wildlife habitat destruction, human expansion, and routine global travel keep increasing the likelihood that another viral pandemic will occur again within the next few decades. Beta coronaviruses are an incredibly diverse family of viruses observed across Asia, Europe, and Africa, that have proven capable of zoonotic spillover into humans as they have caused multiple worldwide outbreaks over the last two decades. We still lack the fundamental understanding of the molecular and genetic factors that dictate the molecular compatibilities that determine which beta coronaviruses are most likely to jump into humans in the future. The ability of SARS-like beta coronaviruses to utilize ACE2 as a receptor for cell entry is a major factor determining the extent of coronavirus tropism across species or within the tissues of an organism. While SARS-CoV-2 has been heavily studied, almost nothing is known about most other members of this virus family. Traditional studies can only test a handful of conditions at a time, incompletely sampling the vast range of relevant experimental conditions, particularly for the hundreds of uncharacterized beta coronaviruses. Large- scale, minimally-biased, cell-based entry assays are needed to model how these factors converge to dictate the probability of infection. We will pair new methods in cell engineering and synthetic biology with DNA-sequencing enabled multiplex genetic assays to perform a series of large-scale infection assays revealing the factors determining susceptibility to beta coronavirus entry. These large-scale experiments will reveal how ACE2 sequence and cell surface density impact the efficiency of virus entry. By testing a library of receptor binding domain sequences identified from ecological surveillance of bat coronaviruses, we will identify which viruses possess sufficient affinity to human ACE2 to potentiate cross-species transmission, and create a catalog describing all of the different ways these viruses have evolved their sequences to engage ACE2. By modeling the relationship between spike and ACE2 protein sequence, expression level, and efficiency of cell entry, we will identify potential animal reservoirs for SARS-CoV-2 and other SARS-like bat coronaviruses, and predict which viruses have sufficient binding with human ACE2 to potentially spark the next pandemic.",,2025,Case Western Reserve University,241500,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Vector biology",2023 +P21682,1R21TW012608-01,Advancing One Health Data Capture at the Point of Zoonotic Spillover in the Congo Basin Forest Perimeter,"Project Summary Due to human encroachment on the fragile ecosystems of the Congo basin forest perimeter, spillover of zoonotic pathogens into border communities have proliferated and resulted in worldwide implications. The region of the Bwindi Impenetrable Forest, located in the southwestern corner of Uganda bordering the Democratic Republic of Congo (DRC) is a biodiversity hotspot harboring among the largest number of primate and bat species of any forest in Africa. It is also situated in one of the most densely human populated regions of Africa. Healthcare facilities in this region remain vigilant for an outbreak of Ebola virus disease (EVD) or Marburg hemorrhagic fever (MHF). This is especially timely given the recent confirmed outbreaks of EVD in neighboring districts. Utilizing a One Health approach, this project will build an essential surveillance infrastructure for investigating ebolavirus and other zoonotic disease spillover events by developing an integrated mHealth system that allows healthcare providers to monitor outbreaks of disease in both humans and wildlife simultaneously. The goal of this surveillance system is to improve detection of zoonotic spillover in the Bwindi region and help to answer decades long questions about the ecological scenarios supporting ebolavirus emergence, enabling forecasting that could help prevent future outbreaks. Specifically, during the R21 phase of this project we will: (1) develop a Village Health Team (VHT) data collection system to capture AFI and wildlife morbidity / mortality information in remote forest settings using a One Health smartphone based APP and community-based SMS system; (2) develop a passive geo-location system using cell-phone tower triangulation with machine learning optimization that can be implemented across smartphone and non-smartphone-based technologies to improve accuracy in localization of outbreaks; and (3) create an integrated One Health AFI outbreak alert system operational in the Bwindi region, optimized for rapid and accurate detection of outbreaks. During the R33 phase of this project we will: (1) refine, expand and evaluate the tiered mHealth surveillance platform for improved longitudinal AFI case identification; and (2) utilize the Bwindi mHealth surveillance system to investigate the epidemiology of ebolavirus exposure associated with wildlife contact in the region. This project is well integrated with existing NIAID funded AFI surveillance programs and collaborates closely with the Ugandan Ministry of Health. This project will provide an optimal scenario for rigorously evaluating the benefits of adding an mHealth component to long term zoonotic disease monitoring, benefiting the sustainability of all developed platforms.",,2025,University Of California At Davis,213850,Animals | Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Digital Health,,,United States of America,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Disease surveillance & mapping | Communication,2023 +P21683,5R01AI152246-04,Structure-based Vaccine Design for CCHFV,"Project Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) causes a life-threatening tick-borne disease in humans. The disease presents as a severe form of hemorrhagic fever with a case fatality rate of 10â€Â""40%. CCHFV outbreaks have spanned a wide geographic area ranging from Western and Central Asia, the Middle East, Africa and Southern Europe. Increasing global temperatures, migratory birds, and the international livestock trade have all potentially contributed toward the spread of Hyalomma ticksâ€Â""the primary vector for CCHFV. Expanding endemic zones, widespread morbidity and significant mortality make CCHFV an acute threat to public health and thus is listed as a NIAID Category A priority pathogen. The viral genome encodes a glycoprotein precursor that is processed into two structural glycoproteinsâ€Â""Gn and Gcâ€Â""and two secreted glycoproteinsâ€Â""a mucin-like domain and GP38. Protective antibodies have been isolated that target Gc or GP38, suggesting that these two proteins should be given priority for vaccine development. Here we propose to engineer Gc- and GP38-based immunogens that focus the immune response onto broadly conserved epitopes that are capable of eliciting protective antibody responses. To accomplish our goal, we will structurally characterize CCHFV glycoproteins and their interactions with human-derived antibodies, rationally engineer vaccine antigens based in part on the structural information, and characterize the immune responses elicited by these antigens in animal models. These results will be used to guide further improvements of the immunogens, including display on self-assembling multi-valent nanoparticles, and the most promising candidates will be evaluated in a lethal murine model of CCHFV challenge. Given our expertise, unique reagents, and preliminary data, we are confident that we can deliver a state-of-the-art subunit vaccine candidate with the potential to induce cross-reactive protective antibodies, thereby satisfying an unmet need against this NIAID Category A tick-borne pathogen.",,2025,University Of Texas At Austin,428507,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +P21684,1F31AI174753-01A1,Defining the protective or pathologic role of antibodies in Post-Ebola Syndrome,"PROJECT SUMMARY Survivors of Ebola virus disease (EVD) have reported a wide range of symptoms following recovery from infection. These long-term sequelae are severe enough to interfere with their daily lives and are now collectively referred to as post-Ebola syndrome (PES). Although post-viral symptoms have posed a serious problem in the Ebola outbreaks of 1995 and 2013-2016, little is known about the underlying mechanism of PES pathogenesis. Ebola virus (EBOV) RNA has been found in immune-privileged sites, such as the eye and semen, so it is suggested that the virus may persist in tissues to cause continued antigenic stimulation over time. However, not all cases of PES can be attributed to viral persistence. Most of the symptoms that survivors experience are autoimmune-like, the most common being arthralgias and myalgias. Autoantibodies against common human proteins have also been found in survivor serum, alluding to virus-induced autoimmunity. We hypothesize that both virus-specific and autoimmune antibody responses play a role in the development of PES. Through a collaboration with Dr. John Schieffelin at Tulane University, we propose to analyze an existing cohort of EVD survivors and their household contacts from Sierra Leone that have been clinically characterized for development of PES. Our preliminary findings revealed that antibodies against the immunodominant antigen, the Ebola glycoprotein (EBOV GP), in asymptomatic EVD survivors were qualitatively different from survivors experiencing musculoskeletal manifestations of PES. Specifically, antibodies from asymptomatic individuals induced higher levels of antibody-dependent complement deposition and monocyte-mediated phagocytosis, but not neutrophil- mediated phagocytosis, and differed in NK cell activation profiles compared with individuals with PES. In addition, our data has also revealed that IgG1 levels against dsDNA, HSP-60, citrullinated histone, and IFNα are elevated in EVD survivors and GP-seropositive household contacts (HHC) compared to GP-seronegative HHC, indicating a correlation between autoantibodies and EBOV infection. Thus, the purpose of this proposal is to further investigate the role of both virus-specific and autoimmune antibody-mediated innate immune cell activation in PES, and whether this role is protective or pathologic. To do so, we propose to analyze antibodies for induction of innate effector function against EBOV-specific proteins in Aim 1 and Aim 2 will focus on the identification of potential autoimmune antibody responses that are elevated in individuals with PES. Together, these aims will address the role of qualitatively different antibodies with varying specificities in shaping susceptibility to/protection from the development of PES and may help to identify potential therapeutic targets to provide proper and effective treatment to EVD survivors suffering from PES. In addition to providing expertise in immunology, virology, and Ebola virus disease, my sponsor and co-sponsors, Drs. Bronwyn Gunn, John Schieffelin, and Anthony Nicola have developed a comprehensive training plan aimed at providing me with the necessary skills needed for me to succeed in this proposal and as a research scientist.",,2025,Washington State University,43934,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2023 +P21688,1R43AI179320-01,High throughput screening and drug discovery for antagonists of the Ebola VP40 protein assembly,"PROJECT SUMMARY This R43 proposal answers the call of the RFA PA-22-176 for assay development and chemical probe screening by addressing the unmet need for development of antiviral treatments for Ebola patients through an innovative high-content small molecule screen for antagonists of the Ebola VP40 matrix protein. There is a need for a fast-acting therapy that is independent of the immune system and targets essential viral proteins. Such a novel therapeutic is anticipated to enhance the survival probability for infected people in hot zones of an Ebola outbreak. We chose to target EBOV VP40 because it is absolutely required for EBOV particle assembly at the cell membrane, is capable of budding virus- like particles (VLPs) when expressed in isolation and VP40 protein-protein interaction domains have been structurally determined. Further guiding this application is our published pilot screen which established proof-of-concept by demonstrating the accessibility of Ebola VP40 protein-protein interactions to sangivamycin, a dual acting small molecule antagonist of both EBOV VP40 assembly of virions and the viral replication machinery. Given this success and due to anticipated complications with efficacy and MOA studies inherent to compounds with dual targets, our Specific Aims propose to screen a library of ~123,000 small molecule compounds to identify antagonists of VP40 accumulation at the cell membrane for VLP formation and release from cells through a fully automated, quantitative, and high-content assay. The assay has been vetted to quantify the effect of small molecules on the cellular distribution of a fluorescent VP40 expressed in 293T cells. Hits validated as dose-dependent by qHTS and displaying low cytotoxicity will be further prioritized based on their absolute requirement for VP40 in antiviral mechanism of action through counter screening with the VP40- independent minigenome assay. Lead compounds also will be prioritized by their favorable ADMET profiles. Our proposed critical path anticipates identifying 2-4 dose-dependent, VP40- selective antagonists with potent antiviral activity that display low cytotoxicity for future medicinal chemistry and preclinical development.",,2025,"OYAGEN, INC.",299000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21689,5K08EB033409-03,Development of Optofluidic Resonators for Filoviral Detection,"Project Summary/Abstract This proposal describes a 4-year career development plan for the PI, Dr. Abraham J. Qavi, MD, PhD, with the goal of preparing him for an independent research career as a physician scientist. This plan includes expand training opportunities and a pathway to an independent career that includes the development and implementation of sensor technologies and its application towards filoviruses, namely Ebola. The PI graduated with degrees in Biochemistry & Molecular Biology and Chemistry from the University of California, Irvine. He then enrolled in the Medical Scholars Program at the University of Illinois at Urbana-Champaign, where he earned his MD and PhD in Chemistry. Dr. Qavi continued his medical training as part of the Clinical Pathology Physician Scientist Training Program at Washington University in St. Louis and the Barnes-Jewish Hospital consortium. During his residency elective time, he began research in the laboratory of Dr. Lan Yang, who will serve as his co-mentor together with Dr. Amarasinghe. Dr. Yang is the Edwin H. and Florence G. Skinner Professor of Electrical & Systems Engineering, and an internationally renowned researcher in photonics. In 2019, Dr. Qavi added an additional training component under the co-mentorship with Dr. Gaya Amarasinghe, Professor of Pathology & Immunology, to expand the application of his previously developed sensor technology to infectious disease reach. The goal of this study is the development of a rapid, multiplexed optofluidic sensor platform for the rapid detection of pathogens, with an initial focus on Ebola. Filoviruses, such as Ebola, are among the most lethal human pathogens, with high case fatality rates during outbreaks. Critical in the identification and management of outbreaks are robust detection methods that can be implemented rapidly and sensitively. To address this critical need, Whispering Gallery Mode (WGM) sensors will be leveraged. WGM devices are a class of optical sensors in which light is confined within a micron-scale volume. These devices have incredibly high sensitivity, small sensor footprint, ease of integration with conventional electronics, and low fabrication costs. Microbubble resonators (MBRs), a subclass of WGM sensors, offer the advantages of conventional WGM devices while enabling coupling of optical and the fluidic components into a single component. The goal of this proposal is the use of an optofluidic sensor platform based on MBRs for the rapid, multiplexed detection of Ebola. The workflow and advancements, including MBR development, engineered antibodies, biophysical validation and multiplexing, will provide the framework to extend the work beyond the initial goals and promote facile transition to an independent career for Dr. Qavi.",,2026,University Of California-Irvine,189713,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P21690,1R01AI174645-01,Dynamics and mechanisms of filovirus envelop glycoproteins,"SUMMARY The increasing frequency and severity of Ebola outbreaks demands an expanded repertoire of treatments and preventative measures. Answering this unmet need will require a deeper understanding of the molecular mechanisms underlying filovirus replication. In particular, the dynamic events that occur during filovirus envelope glycoprotein (GP)-mediated membrane fusion during entry into cells have evaded elucidation for decades. Previous studies have identified proteolytic cleavage of GP, receptor binding, and the chemical environment of the late endosome as being critical. But the molecular mechanisms by which these events and variables promote GP-mediated membrane fusion are not known. As a result, a complete and specific model of filovirus fusion, which integrates host factors, environmental conditions, and GP conformational changes currently does not exist. Therefore, filovirus entry continues to be an unutilized target for inhibitors. Our long-term goal is to develop a complete mechanistic model of GP-mediated membrane fusion. Our recent publications, in which we demonstrate the power of single-molecule fluorescence methods in elucidating the conformational dynamics of EBOV GP on the surface of virions, demonstrate our initial efforts toward this end. Here we aim to build on this success by proposing a multidisciplinary study involving virological, cellular, structural, and biophysical methodologies to elucidate the dynamics and mechanisms of GPs from multiple filoviruses. We will characterize the mechanisms by which conformational changes, host factors, and environmental variables facilitate filovirus membrane fusion and entry into cells. Completion of the proposed research will provide mechanistic insights into filovirus entry and the viral and host targets that could be exploited with novel therapies and immunogens.",,2027,UNIV OF MASSACHUSETTS MED SCH WORCESTER,802744,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21691,1UH2AI169710-01A1,Elucidating mechanisms of interferon gamma that protect against Ebola virus infection,"Abstract Filovirus outbreaks/epidemics occur sporadically, but with increasing frequency and intensity. With no current approved filovirus therapeutics, the recent Ebola virus (EBOV) outbreaks emphasize the need for effective treatments against this highly pathogenic family of viruses. A better mechanistic understanding of effective early immune responses to EBOV will identify potential immunological approaches for controlling this infection and associated disease. Interferon gamma (IFN-γ) elicits production of antiviral proteins that control of virus replication and stimulates and activates cellular immune responses. In a series of recent studies, we demonstrated that IFN-γ profoundly inhibits EBOV infection of macrophages, an important early cellular target for the virus. We also showed that IFN-γ protects mice from EBOV challenge when mice were treated 24 hours prior to or after infection. These findings provide evidence that the immune responses elicited following IFN-γ stimulation effectively control EBOV infection and disease. Here, we will explore the contribution of both innate and cellular immunity to IFN-γ- mediated protection. In total, studies proposed here will provide critical mechanistic insights into the efficacy of this immune pathway to control filovirus infections.",,2024,University Of Iowa,231750,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2022 +P21692,7F31AI157079-02,Leveraging protein dynamics to drug filovirus protein-nucleic acid interactions using simulations and experiments,"Project Summary Many proteins are classified as ‘undruggable,’ especially those that engage in protein-protein and protein- nucleic acid interactions as they interact with their binding partners through flat interfaces. This is particularly true in the case of many viral proteins that interact with host factors and viral nucleic acids and lack enzymatic activity. In the highly lethal filovirus family one protein, viral protein 35 (VP35) is primarily responsible for the viruses’ immune evasion. In this family the ebolavirus is the most fatal with a case fatality rate at 66% in recent outbreaks. Thus, there is a great need for discovering new therapeutic targets in this family of viruses. Although proteins are known to be dynamic, only recently has considering protein dynamics for drug design become tractable through advances in molecular dynamics methods. As such, discovering ‘cryptic’ pockets that are absent in available structures but open due to protein dynamics could provide new druggable sites. Here, I propose integrating atomically-detailed simulations, biophysical, and cellular experiments to understand the cryptic pocket in viral protein 35 (VP35) from the highly lethal filoviruses. VP35 plays multiple essential roles in these viruses’ replication cycles, including binding the viral RNA genome to block hosts’ innate immunity and acting as a polymerase co-factor. However, available crystal structures of VP35 lack appealing pockets for drug discovery and the protein has so far remained undruggable. We recently have applied adaptive sampling simulations to preferentially sample conformations with large pocket volumes. This revealed a potentially druggable cryptic pocket. While the pocket does not directly coincide with the crucial interface for binding RNA, we have shown that the pocket can allosterically modulate RNA binding and is a good drug target. To further test this, I will use a thiol labeling experiment to directly test for this cryptic pocket in VP35 homologs. Then, to determine if this cryptic pocket is allosterically coupled to function, I will test if stabilizing the open form allosterically disrupts RNA binding using a fluorescence anisotropy assay. I will then screen for small-molecule inhibitors of RNA binding that bind to the cryptic pocket and confirm this by X-ray crystallography and mutational tests. Finally, I will assess the effect of stabilizing the open pocket on VP35’s interferon antagonism, and viral replication activities using an in-vitro ATPase assay and cellular minigenome assay. Successful completion of these experiments will further the National Institute of General Medical Sciences’ mission to increase our understanding of biological processes for laying the foundation of advancing disease treatments. These results will demonstrate the power of fusing simulations and experiments to characterize hidden conformations and dynamics, uncovering cryptic pockets and allostery that present new therapeutic opportunities.",,2023,University Of Pennsylvania,30490,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21693,4R44AI150263-03,A modular platform for infectious disease surveillance at point-of-need.,"ABSTRACT We propose to develop a point-of-need system for differential molecular identification of filoviruses from syndromically similar infections. Our goal is to enable rapid, sensitive, and specific identification of quarantinable infections to reduce nosocomial risk and improve outbreak response. The platform will simultaneously test 12 genomic markers at the genus and strain level using a modular microfluidic design that allows for rapid panel update and expansion. In Phase I we will develop an assay for pan-filovirus (pFi), followed by expansion of the panel and system integration in Phase II. The expanded panel will add pan-flavivirus (pFa) and pan-Plasmodium (pPa) detection as well as strain-specific targets for Ebola, Marburg, Dengue, Yellow Fever, and Malaria. Strain specific tests will enable better patient triage/treatment during an outbreak and improve disease surveillance in non-outbreak settings. The panel will require a 50 μL sample of whole blood and will achieve highly specific detection in < 30 minutes. To achieve this goal, we will combine Redbud Labs’ expertise in microfluidics and systems with the diagnostic development expertise of the Diagnostics Program at PATH (Seattle, WA), and the VHF testing/processing capabilities of the Connor Lab at Boston University (part of the BSL-4 facilities at NEIDL).",,2024,"REDBUD LABS, INC.",998995,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21694,5R21AI159703-02,Ebola virus infection of the female reproductive system,"SUMMARY/ABSTRACT Ebola virus (family Filoviridae) is the causative agent of Ebola virus disease (EVD), which is characterized by hemorrhagic fever in humans, reaching high mortality rates (≥40%). Sexual transmission of Ebola virus from a male survivor to a woman was first documented during the large 2014-2016 West African outbreak. Then this route of infection was reported to be likely responsible for multiple EBOV outbreak flare-ups between 2015 and 2016. Infectivity of the semen of survivors was later documented for at least 179 days after the onset of disease. Mathematical modelling of the contribution of sexual behavior in virus transmission during that same outbreak showed that abstinence, along with infectious patient isolation, could stop an outbreak. As of June 2nd, 2020, the on-going EBOV outbreak in the Democratic Republic of the Congo describes 3463 cases with 2280 deaths, and there are no data available as to which route of infection is primarily responsible of transmission and the situational awareness of survivors to spread EVD. Recently, our group demonstrated that human vaginal epithelial cells are susceptible to infection with Ebola virus, support productive viral replication resulting in a robust proinflammatory response. Furthermore, we evaluated the antiviral efficacy of the vaginal Polyphenylene Carboxymethylene (PPCM) microbicide as a countermeasure and could show suppression of virus replication and virus-induced inflammatory response in these cells. Altogether, these facts support the critical need to develop new experimental models for this route of infection and therapeutics preventing virus transmission during unprotected sexual intercourse. Our long-term goal is to better understand sexual transmission of Ebola virus, and to identify prophylactic methods other than condoms. The objective in this proposal is to investigate Ebola virus pathogenesis in women following sexual transmission using a relevant in-vitro model of the human female reproductive system as well as a susceptible mouse model. Our central hypothesis is that the human female reproductive system is susceptible to Ebola virus infection leading to atypical clinical manifestations of EVD and laboratory characteristics compared to those observed after infection by Ebola virus using other more documented routes of infection. To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Characterize Ebola virus infection and inflammation in-vitro using a model of the human vaginal epithelium cultured at air-liquid interface, (2) Establish an in-vivo model of Ebola Virus Disease (EVD) following intravaginal virus challenge, and (3) Evaluate the protective antiviral efficacy of PPCM in-vitro and in-vivo. The proposed studies will develop novel models for research of filovirus pathogenicity and further develop PPCM as a microbicide for Ebola virus infection.",,2024,University Of Texas Med Br Galveston,237000,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Pre-clinical studies",2021 +P21695,1R21AI169646-01,Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo,"ABSTRACT Bats play an important role as natural reservoirs of numerous RNA viruses with the potential to cause significant harm to humans. In this proposal, we focus on Lloviu virus (LLOV), an under-investigated filovirus that circulates in Schreiber’s bats (Miniopterus schreibersii) in Europe. Although the pathogenic potential of LLOV for humans is not known, the close relationship of LLOV to the highly pathogenic Ebola and Marburg viruses raises concerns that a potential spillover event could lead to an outbreak among humans. LLOV was first detected Schreiber’s bats in Spain in 2002 and then again in Hungary in 2016. Sequence comparison of the Spanish and the Hungarian LLOV RNA genomes suggests that RNA editing by cellular deaminases, such as ADAR and APOBEC, might play a role in LLOV sequence diversification. In this application, we propose to explore if host-mediated RNA editing drives LLOV sequence divergence and evolution in Schreiber’s bats. In Aim 1, we propose to sample Schreiber’s bats from geographically distinct colonies and obtain LLOV sequence information from infected bats for comparative analysis. We will further develop tools based on highly sensitive droplet RT-PCR and RNA FISH that allow to determine the expression pattern of ADARs and APOBECs in LLOV-infected bat cell culture and in blood samples from infected animals. In Aim 2, based on the determined ADAR and APOBEC expression patterns, we will knockout select ADAR and/or APOBEC genes that might be involved in LLOV RNA editing in the bat cell line and examine the role of these genes in LLOV sequence diversification and viral fitness in serial passaging experiments and cell culture infection studies. Upon completion of this work, we will have revealed whether host-specific RNA editors are the drivers of LLOV evolution in bat cells. This work will contribute to our understanding of host-driven viral sequence divergence and might help assess the risk of potential LLOV spillover events from bats to humans through host-driven changes in viral sequences.",,2024,Boston University Medical Campus,243800,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Immunity | Animal source and routes of transmission | Vector biology,2022 +P21696,5R01AI156866-04,Spillover of Ebola and other filoviruses at ecological boundaries,"More than half of all infectious disease outbreaks across the globe are zoonotic, involving pathogen spillover from animal reservoirs to humans. Ebola and other filoviruses rank among the most deadly zoonoses. Recent large outbreaks with mortality in the thousands both in humans and wildlife underscore the pressing need to better understand the factors promoting filovirus spillover. Although spillover is commonly defined as a pathogen crossing species boundaries, there are relatively few empirical studies or modeling frameworks that explicitly consider ecological boundaries across which spillover occurs. Crossing ecological boundaries involves processes that occur at many levels of organization: physiological processes at the individual level, interspecies interactions between individuals at the population level, interactions between populations of different species at the community level, and interactions between ecological communities within landscapes. Processes accelerating spillover often involve human activities such as habitat encroachment and land conversion, which are themselves ultimately driven by socioeconomic factors. In the context of Ebola and other filoviruses in Africa, we will develop the data sets, theoretical models and statistical tools needed for a general descriptive and predictive framework for spillover at ecological boundaries. Our project will follow an iterative design where results from mechanistic models are used to refine patterns that we test for empirically, and statistical models of large-scale data allow us to more realistically parameterize mechanistic models. Our work will test the generality of specific theories that so far have been applied only to a limited number of study systems. For example, ours will be among the first attempts to test the influence of Schmalhausen’s law -- an evolutionary theory that may explain the tendency for large outbreaks to occur at the edges of species ranges or during unusual weather conditions and which to date has primarily been investigated in the context of malaria -- in pathogens that rely on direct transmission. This work will demonstrate how new methods can provide unifying insight into patterns in critically important disease transmission systems and will enhance our ability to predict spillover of both filoviruses and many other zoonotic pathogens. Note that no human subjects, biohazards, or select agents will be involved in this project.",,2025,Oklahoma State University Stillwater,383897,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21699,5U01AI160397-02,"Defining molecular mechanisms of combination adjuvants: a systems immunology, transcriptomics and imaging approach","PROJECT SUMMARY/ABSTRACT In this proposal we will define molecular and cellular mechanisms of different combinations of known adjuvant components MPLA (a TL4 agonist), CpG (a TLR9 agonist), agonists of cGAS-STING and NOD1/2 pathways, and a squalene-in-water emulsion (AddaVAXâÂ""¢). Our overall Aim is to provide a detailed analysis of every combination of these using high throughput in vitro and in vivo assays, followed an in-depth analysis of two combination adjuvants using live cell imaging and single-cell mRNA sequencing of draining lymph nodes after vaccination. Initially, 96-well based in vitro assays of innate and adaptive immune system activation will be used to profile different adjuvants components, both individually, and in different combinations and concentrations. These assays will comprise: 1) activation of TLR, NOD and STING signaling pathways using primary dendritic cells (DCs), T and B cells from reporter transgenic mice; 2) in vitro activation of naïve B cells to monitor their differentiation into plasma cells and class switching. We anticipate some of the adjuvant combinations will have synergistic effects that differ from the sum of the effects when used individually. Next, based on performance in vitro a subset of combination adjuvants and their individual components will be evaluated as adjuvants for model vaccine antigens (influenza hemagglutinin H1, filovirus (EBOV) glycoprotein and SARS-CoV-2 spike) in vivo in mice. Immunogenicity metrics will comprise: 1) antibody dynamics and durability, isotype, avidity and breadth of cross-reactivity using protein microarrays; 2) flow cytometry of antigen-specific B cells to assess differentiation and cross-reactivity; 3) T cell recall assays to define Th1/Th2/Th17 cytokine profiles; 4) neutralization by sera of live influenza, SARS-CoV-2 and VSV-pseudotyped with EBOV glycoprotein. This will provide a comprehensive cellular and molecular profile associated with each combination adjuvant. Two combination adjuvants (and their individual components for comparison) will be selected for a deep analysis using: 1) transgenic mice that allow Ca2+ fluxes in live CD4 T and B cells and DCs to be visualized using 2- photon microscopy. Combined with techniques of whole tissue imaging, we will monitor adjuvant-driven T cell and DC mobilization, motility and interactions in live draining lymph nodes; 2) using single-cell RNAseq technology (10x Genomics Inc) of cells in draining lymph nodes, we will define cell composition and phenotype, cellular interactions and spatial organization. We will perform a deep analysis in Year 1 on the combination adjuvant CpG/MPLA + AddaVAX (TLR9 and TLR4 agonists in a squalene-in-water emulsion) since we have already shown this is a powerful combination adjuvant. A second combination adjuvant will be selected for deep analysis based on data generated in the in vitro and in vivo assays described herein. Together these complementary deep approaches will provide an unprecedented level of molecular and cellular detail of two highly effective combination adjuvants. Overall, we anticipate these data will help guide the future design of vaccines where the immune response required can be tuned according to the particular pathogen in question.",,2025,University Of California-Irvine,575733,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Orthomyxoviridae,H1,Unspecified,,,,,,,COVID-19 | Ebola virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21700,272201700040I-0-759302200002-1,Task A66: Rodent models for testing therapeutics against filoviruses,"This contract provides for the development and standardization of small animal models of infectious diseases, and may include efficacy testing of candidate products, including GLP studies to support licensure.",,2023,University Of Texas Med Br Galveston,472205,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2022 +P21701,75N93020C00040-P00003-9999-1,Advanced Development of Vaccines for Filoviruses ,"To support the advanced development of multivalent vaccine candidates for filoviruses and Lassa Fever. This contract aims to formulate a multivalent vaccine that provides protection against several pathogens, including Ebola virus, Marburg virus and Lassa Fever. It may support cGMP manufacture of a stable lyophilized vaccine formulation and preparation and submission of an IND to support eventual clinical evaluation.",,2026,AURO VACCINES LLC,1239978,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P21703,5R21AI151717-02,The role of macrophage podosomes in Ebola virus pathogenesis,"PROJECT SUMMARY Ebola virus (EBOV) is an emerging, highly pathogenic virus associated with increasingly more frequent outbreaks of hemorrhagic disease in human populations. Approved countermeasures to prevent or treat EBOV disease are currently limited. Macrophages are the initial cells targeted by EBOV, and yet, little is known about the exact nature of EBOV-macrophage surface interactions and subsequent uptake into the cell. Due to their migratory properties, macrophages are also believed to rapidly disseminate the virus to distant tissues and organs despite the lack of experimental evidence. We have preliminary data showing that EBOV depends on podosomes, mechanosensitive adhesive structures used by macrophages to migrate through tissues and sample antigens, to enter macrophages. The data also shows that EBOV replication increases macrophage locomotion through a fibrillar 3D matrix and reduces podosome number, suggesting that the virus actively transforms infiltration of tissues by these cells. This proposal aims to examine the interactions between EBOV and podosomes. In Aim 1, we will determine whether podosomes serve as ports for EBOV entry into human macrophages. In Aim 2, we will characterize migratory and invasive properties of macrophages challenged with EBOV. In Aim 3, we will assess host resistance to systemic infection with EBOV in a mouse model of EBOV disease devoid of functional macrophages. Our findings will establish a new model of interactions between EBOV and macrophages, laying the groundwork for further investigations into pathogenesis of filoviruses. Importantly, these discoveries may lead to new areas of development of novel countermeasures targeting EBOV and related viruses.",,2023,TEXAS BIOMEDICAL RESEARCH INSTITUTE,247500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21704,5U01AI151814-03,EpiCenter for Emerging Infectious Disease Intelligence,"Project Summary/Abstract: The Epicenter for Emerging Infectious Disease Intelligence brings together a consortium of leading research institutions to advance an understanding of viral emergence from wildlife into humans living in forest and rapidly urbanizing ecosystems. Our work will enhance preparedness for disease emergence events in the Congo Basin and Amazon Basin forest regions and facilitate response efforts at the source of emergence. Our multidisciplinary team has internationally recognized expertise in infectious disease epidemiology, virology, human health, animal health, medical entomology, microbiology, and disease modeling. Our proposed activities integrate human, animal, and vector surveillance to enable insight into cross-species disease transmission and facilitate responsiveness to evolving needs that impact country, regional, and global emerging infectious disease risk. In our initial work, we propose to investigate the epidemiology of arboviruses and filoviruses, which include emerging viruses currently threatening global health security. We will evaluate disease transmission dynamics at the primary stage of emergence in humans, in forest communities where people are highly susceptible to virus spillover from wildlife and mosquitos. We will also investigate these viruses in the second stage of emergence, in urban centers peripherally connected to forests, where viruses have adapted to human-to-human transmission (by direct or vector-borne transmission). Targeted filoviruses and arboviruses at proposed sites in Uganda and Peru represent a range of emergence histories, from recent emergence events, to seasonal and annual re- emergence events, to introduction events where viruses have adapted to entirely new ecosystems, vectors, and vertebrate hosts. Research at these sites will advance our understanding of cross-species transmission for viruses across this spectrum of emergence. Our work will optimize best practices in acute febrile illness surveillance in high-risk communities coupled with wildlife and entomologic risk characterization studies to facilitate deployment of next generation techniques in early detection of virus emergence and monitoring of sustained transmission in at-risk communities. Our consortium has a demonstrated commitment to strengthening international capabilities for emerging infectious disease research in resource-limited countries. We are well- poised to contribute to important advances in capacity in the Amazon and Congo Basin forest region with partners in Uganda and Peru for completion of our proposed project and long-term sustainability for the greater region and across the Emerging Infectious Disease Research Center network.",,2025,University Of California At Davis,1581195,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Disease transmission dynamics",2020 +P21705,5R01AI146172-04,Dissecting catalytic and regulatory functions of nonsegmented negative strandRNA viral polymerases,"Non-segmented negative strand (NNS) RNA viruses, such as rabies virus (RABV), human respiratory syncytial virus (HRSV), human parainfluenza virus type 3 (HPIV3), and Ebola virus (EBOV), pose continuing threats to human health, but there are currently no established prophylactic and/or therapeutic countermeasures against most NNS RNA viral diseases. NNS RNA viruses possess a multifunctional RNA-dependent RNA polymerase (RdRp) large (L) protein, which catalyzes all enzymatic reactions required for viral RNA biogenesis (e.g., RNA synthesis, 5′-capping, cap methylation at the guanine-N7- and ribose-2′-O-positions, 3′-polyadenylation). All these enzymatic activities of the L proteins are unique and potentially druggable. Our goals are to elucidate the molecular mechanisms of RNA synthesis and processing with the L proteins and to develop anti-viral agents against them. To dissect the roles of the L proteins in RNA biosynthesis, we have developed a number of in vitro rhabdoviral RNA synthesis and processing systems for prototypic vesicular stomatitis virus (VSV) and RABV. Using these systems, we discovered that rhabdoviral L proteins catalyze unconventional mRNA capping with a novel GDP polyribonucleotidyltransferase (PRNTase, EC 2.7.7.88) domain. However, the mechanisms of pre- mRNA capping and methylation coupled to mRNA chain elongation remain largely unknown. Furthermore, virus- specific functions of L proteins have not been studied. We hypothesize that L proteins catalyze common enzymatic reactions via evolutionary conserved elements, but manifest virus-specific functions via diversified elements. This hypothesis will be rigorously tested by the following specific aims: to elucidate the mechanisms of (1) co-transcriptional mRNA maturation by rhabdoviral L proteins, (2) cap formation by pneumoviral and paramyxoviral L proteins, and (3) transcription and replication by filoviral L proteins. In Aim 1, we will determine the timing and order of pre-mRNA processing by the VSV L protein during mRNA chain elongation, leading to a new model of co-transcriptional mRNA maturation by L proteins of rhabdoviruses and, by extension, other NNS RNA viruses. In Aim 2, we will reveal common and diversified functions of putative PRNTase and methyltransferase domains of the HRSV and HPIV3 L proteins in mRNA cap formation. In Aim 3, we will provide a novel model for genome replication by the EBOV L protein that is significantly different from that by other NNS RNA viral L proteins. Collectively, the proposed studies will open up a new frontier in understanding how diversified NNS L proteins carry out each step of RNA synthesis and processing together with their cognate co- factor proteins. Our studies will provide foundations for the future development of antiviral agents targeting unique L domains of these significant NNS RNA viruses.",,2024,University Of Toledo Health Sci Campus,347625,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P21706,5R21AI154336-02,Tunneling nanotubes as an alternate route of Ebola virus dissemination,"Ebola virus (EBOV) is an emerging, dangerous virus that causes increasingly more frequent outbreaks of a systemic, hemorrhagic disease in human populations. Approved countermeasures to prevent or treat EBOV disease are currently limited. Macrophages are the initial cells targeted by EBOV, and due to their migratory properties are believed to rapidly disseminate the virus to distant tissues and organs despite the lack of experimental evidence. In current models, EBOV propagates infection through the cell-free form, where virus particles enter the cell, replicate the genome, and then assemble/egress to challenge neighboring cells. We have preliminary data suggesting that EBOV may exploit an alternative mode to spread infection (in parallel with the established model): viral nucleocapsids via tunneling nanotubes (TNTs), an actin-based intercellular communication system that allows direct exchange of cytoplasmic material between connecting cells. EBOV infection induces formation of intercellular connections containing virus nucleocapsid protein in primary human endothelial cell and macrophage populations. These connections support cell-to-cell transfer of the nucleocapsid protein in the absence of the virus. The data also show that EBOV can efficiently replicate in endothelial cells devoid of factors critical for virus entry, after initial retardation, and that the replication is compromised in cells depleted of host M-Sec, a central factor for TNT formation. This proposal aims to interrogate the interactions between EBOV and TNTs through two Specific Aims. In Aim 1, we will determine if TNTs are the intercellular connections induced by EBOV to spread infection in human endothelial cells and macrophages. In Aim 2, we will determine if EBOV spreads infection through intercellular transfer of nucleocapsids. Our discoveries will establish an alternate model of EBOV dissemination within the host, laying the groundwork for further investigations into pathogenesis of filoviruses. Importantly, these findings may lead to development of novel strategies to target EBOV and related viruses.",,2024,TEXAS BIOMEDICAL RESEARCH INSTITUTE,247500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21707,1G20AI174740-01,Improving The Scripps Research Institute BSL3 Capabilities to Combat Viruses of Pandemic Concern,"Project Summary/Abstract The goal of the application “Improving The Scripps Research Institute BSL3 Capabilities To Combat Viruses Of Pandemic Concern” is to renovate and upgrade The Scripps Research Institute (TSRI) current ABSL3 and BSL3 facilities. This will enhance TSRI research capabilities to combat RNA viruses of pandemic potential. TSRI has ~ 2,000 sf dedicated to ABSL3 and ~ 1,500 sf dedicated to BSL3. Currently, these facilities support research projects from eight TSRI faculty whose combined areas of expertise cover research on RNA viruses of pandemic potential, including Bunyavirales, Coronaviridae, Flaviviridae, Filoviridae and Togaviridae. In addition, the facilities are supporting several projects sponsored by pharmaceutical companies. The specific studies have strong translational components aimed at developing antiviral drugs and immunotherapeutics against these RNA viruses. TSRI ABSL3 and BSL3 suites, located in the Molecular Biology Building (MBB), have been operating 24/7 since the last renovations in 2004. The existing mechanical systems have been maintained beyond ASHREA equipment life expectancy for the La Jolla, Ca. coastal climate. In addition, the original design from 1985-87 has resulted in underutilization of ~160 sf in the ABSL3 and ~400 sf in the BSL3. To correct these deficiencies, TSRI has completed a conceptual design with FPBA Architects & tk1sc Mechanical Engineers. This plan includes replacing the aging HVAC systems of the ABSL3 and BSL3 space to increase airflow capacity with N+1 redundancy and update the HEPA filtration system of the ABSL3. In addition, the project will modernize the biocontainment suites by increasing holding capacity (ABSL3), creating a select agent isolation room (BSL3), and installing a new sterilizer (ABSL3). The current ABSL3/BSL3 facilities lack imaging, cell sorting, and single cell analysis capabilities. To remedy these deficiencies, we propose adding to the facility the EVOSTM Imaging System, the SH800S Cell Sorter and the Chromium iX system. These improvements will help to address the increasing demands by TSRI faculty for ABSL3/BSL3 space, time and improved functional capabilities, while ensuring the highest level of safety during daily operations of the facility. Moreover, research activities proposed under the Antiviral Program for Pandemics (APP) U19AI171443 AViDD Grant Application, will greatly benefit from the proposed improvements to the current TSRI ABSL3 and BSL3 facilities. The project will be managed by a well-integrated and highly qualified team, including leaders from Facilities Construction and Engineering, the Institutional Animal Program and Resources, EHS and Biosafety, the Executive VP Office, and investigators directly involved in ABSL3/BSL3 research activities. In addition, the application has the unwavering support of the TSRI leadership.",,2025,"SCRIPPS RESEARCH INSTITUTE, THE",3869562,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Coronavirus | Filoviridae | Flaviviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",,2022 +P21709,5R01AI151144-02,Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.,"ABSTRACT This project focuses on understanding the role that the unique physiology of bats plays in their ability to act as host reservoirs for diseases that can spill over to humans. The project will be carried out under field conditions in Uganda on three species of bats that have varying links to the spread of Ebola virus (EBOV) to humans. By comparing the ability of these three species of bats to respond to Ebola-like immune challenges, this work will help identify the characteristics that contribute to spillover risk. In the long term, this work will help identify host species for EBOV and other related viruses that present risk to humans. It will also help explain how different species of bats respond to different types of viral infections. The main focus of this project will be to identify behaviors and molecular pathways that enable reservoir hosts to tolerate infections, providing critical insight into one of the mechanisms that leads to spillover. This work is driven by the hypothesis that some bat species have coevolved with particular types of viral infections and, therefore, have adapted mechanisms to minimize pathology during infection. Bats are globally biodiverse and have many unique ecological and physiological adaptations, including flight and the ability to employ both hypo- and hyperthermic body temperature regulation. This project focuses on three bat species chosen because they are in close contact with humans, their habitats cover the range of EBOV exposure risk, and they have divergent coevolutionary histories with viral pathogens; two of the three species have significant ties to EBOV epidemiology. This project addresses these questions under natural conditions in the field by taking the innovative approach of using EBOV virus-like particles as a proxy for experimental infection with biohazardous pathogens. This project has three specific aims that will allow the achievement of its goals. First, the project tests the hypothesis that specific African bat species will display signatures of EBOV disease tolerance in response to challenge with EBOV virus-like particles, and thus are likely to be natural reservoir hosts. These experiments will provide significant insight into disease tolerance in bats and the potential identity of EBOV reservoir(s). Second, this project tests the hypothesis that bats display variable levels of disease tolerance that depend upon innate immune pathways that have undergone unique evolutionary selection in bats. Third, this project explores whether tolerance of and resistance to viral infection are facilitated by the unique metabolic behaviors of bats, namely that they can depress metabolism and enter torpor to conserve energy and can elevate metabolism and thus temperature during flight. The role of changes in body temperature is poorly understood and these experiments will identify whether these physiological responses contribute to immunological tolerance and resistance in important disease reservoirs. Together, the successful completion of these goals will help determine whether infection tolerance confers on African bat species the ability to serve as reservoir hosts for virulent zoonotic viruses and will identify molecular, physiological, and behavioral mechanisms that contribute to tolerance phenotypes.",,2026,Bucknell University,610710,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +P21710,5R21AI164268-02,Intelligently predicting viral spillover risks from bats and other wild mammals,"PROJECT SUMMARY The transmission or ‘spillover’ of wildlife viruses to humans is a critical threat to global health, with outbreaks of viral pathogens like filoviruses, paramyxoviruses, and coronaviruses all originating in wild mammals. A key outstanding question is whether specific taxonomic groups, such as bats, warrant extra surveillance as ‘special reservoirs’ of viruses that are potentially pathogenic to humans. However, existing host-virus datasets are not sufficiently resolved to predict fine-grain risk for species or genera. An effective response must therefore address two core aims: (i) synthesizing knowledge regarding virus-to-mammal interactions; and (ii) using that knowledgebase to robustly predict future spillover events (i.e., zoonotic risk). To enable robust analysis and reusability of public datasets of NIAID’s Bioinformatics Resource Center (BRC; especially NCBI Virus and Virus Pathogen Resources, ViPR), the project will develop Host-Virus Data Intelligence to address three main problems for data reuse: confidence of the taxonomic assignments of mammals and viruses in observations; confidence in the evidence for proposed mammal-virus interactions; and connecting all the relevant data in published texts that are hidden from existing databases. The project team will construct a novel bioinformatic pipeline that will digitally connect taxonomic knowledge, use it to search dark data to find evidence of potential host-virus interactions, and then link it together using metadata layers (‘data about the data’) to form a more expansive host-virus knowledge graph than previously feasible. The project’s computational approach leverages information extraction methods in natural language processing as well as novel applications of artificial intelligence methods such as probabilistic inductive logic programming. A key anticipated outcome is to expand the dataset of host-virus interactions by 3-fold compared to comprehensive existing datasets. The proposed project will lay the foundation for a new generation of work reusing host-virus interaction data to test previously inaccessible hypotheses about how species’ traits impact viral spillover to humans. Shifting the paradigm to graph-based analyses, compared to purely taxonomic representations of host-virus interactions, will allow researchers to directly investigate the impact of ecosystem structure and human encroachment upon viral loads. Determining whether all mammals have equal risk of viral spillover, or whether some groups have higher taxon-specific zoonotic risk (e.g., horseshoe bats, murid rodents), is critical information for public health workers and epidemiologists. More definitive risk quantification will also help researchers identify which ecophysiological adaptations predispose certain groups to tolerating more viruses, which may in turn lead to clinical treatments by modeling the immune responses of wild mammals. Filling the identified gaps in host-virus knowledge is therefore essential to aid the progress of zoonotic disease research in the wake of COVID-19.",,2023,Arizona State University-Tempe Campus,188045,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing | Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Health Systems Research","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Health information systems",2021 +P21711,1G20AI174733-01,Strengthening the ISMMS research and response capabilities for pathogens of pandemic potential,"The Icahn School of Medicine at Mount Sinai (ISMMS) is an international leader in medical and scientific training, biomedical research, and patient care. The ISMMS is the medical school for the Mount Sinai Health System (MSHS), which includes eight hospital campuses within the New York City metropolitan area that is a major focal point of international travel. The MSHS leveraged its large metropolitan footprint by establishing pathogen discovery and pandemic surveillance activities. The Department of Microbiology maintains robust research programs that are focused on investigating the biology of new and emerging RNA viruses with pandemic potential and developing novel medical countermeasures against these RNA that are focus of the NIH Antiviral Program for Pandemics (APP). These research programs include pandemic preparedness efforts focused seven RNA virus families or orders of greatest pandemic concern, i.e., Bunyavirales, Coronaviridae, Filoviridae, Flaviviridae, Paramyxoviridae, Picornaviridae, and Togaviridae. Since 2017, faculty members of the Department of Microbiology have co-authored over 250 peer-reviewed publications on these viral pathogens of public health concern. The Department of Microbiology is internationally recognized for its influenza research programs, including investigation of highly pathogenic influenza viruses that require enhanced biocontainment facilities and safety protocols. The BSL-3/ABSL-3 biocontainment facilities are essential shared resources that ensure biosafety and biosecurity of RNA viruses of significant public health concern and to safely conduct research investigating the biology of viral pathogens with pandemic potential. Our application is focused on infrastructure improvements to modernize three biocontainment facilities to improve biosafety, improve efficiency of operations, and expand research capabilities. The first aim of the infrastructure improvements focus on upgrades of the HVAC, autoclaves, biological safety cabinets, and ventilated animal caging systems to modernize and improve the efficiency of operations of the biocontainment facilities. The second aim of the infrastructure improvements to improve biocontainment research workflow on pathogens with pandemic potential focus, including BioTek multimode microplate readers, imaging stations, and a Luminex platform for multiplex immunoassays.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,2314456,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Bunyaviridae | Coronavirus | Filoviridae | Flaviviridae | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research on Capacity Strengthening,Institutional level capacity strengthening,2022 +P21712,1R21AI156546-01A1,RNA virus capture of host chemokines: Understanding novel viral mechanisms of immune manipulation,"Unanticipated epidemics of disease caused by RNA viruses that are normally maintained in wildlife species, such as influenza A (ducks, shorebirds), Ebola (fruit bats), Zika (non-human primates), and SARS-related coronaviruses (insectivorous bats) have become an increasing global health threat. One important property of all RNA viruses is their ability to subvert the host immune response. Although RNA viruses have been shown to utilize many divergent mechanisms of immune manipulation, the acquisition of host genes such as chemokines â€Â"" as we have recently demonstrated in a newly discovered RNA virus named Jeremy Point virus (JPTV) â€Â"" is an exceedingly rare event. Our central hypothesis is that this virokine (virus-captured chemokine; ORF6) â€Â"" characterized as an ELR+ CXC chemokine homologue similar to interleukin-8 (IL-8) â€Â"" is fully functional and recruits immune cells to sites of infection. Remarkably, ORF6 was also duplicated during replication and is now evolving into a new gene (ORF5) with an alternate function. The primary goal of this project is to better understand how RNA viruses use gene capture to subvert the vertebrate immune system and cause disease. In Specific Aim 1, we will investigate the function of the JPTV virokine and ORF5 through reverse genetics, advanced immune cell microfluidics, and cross-linking mass spectrometry (XL-MS). We have already cloned, expressed and purified the JPTV virokine by affinity chromatography and demonstrated it has chemotactic activity. Using this purified protein, we will further assess its chemoattractant capabilities by immune cell-based microfluidics to determine if it may act either as an agonist (i.e., bind to immune cell receptors and trigger migration) and/or antagonist (i.e., bind to receptors without triggering migration and thus block the effects of other chemokine agonists) to various immune cells from different hosts, as well as perform XL-MS to identify putative binding partners of the virokine. Lastly, we have recently constructed a reverse genetics system for JPTV, which we will use to investigate the biological properties of mutant viruses with or without the host captured genes. In Specific Aim 2, we will determine the structural relationships of the JPTV virokine to vertebrate ELR+ CXC chemokines by X-ray crystallography and, if necessary, we can also use alternative structural methods such as nuclear magnetic resonance spectroscopy. Importantly, structural determination of the JPTV virokine (ORF6) will also provide the first step in our goal of direct comparison with its subsequent duplication event (ORF5), which we will also target for protein crystallization. To our knowledge, such structural comparisons between a stolen host gene and its duplicate (that has evolved into a different protein) has not been performed and thus would provide a new insight into RNA virus evolution that has never been previously observed.",,2023,University Of Florida,241002,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21713,5R01AI152246-03,Structure-based Vaccine Design for CCHFV,"Project Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) causes a life-threatening tick-borne disease in humans. The disease presents as a severe form of hemorrhagic fever with a case fatality rate of 10â€Â""40%. CCHFV outbreaks have spanned a wide geographic area ranging from Western and Central Asia, the Middle East, Africa and Southern Europe. Increasing global temperatures, migratory birds, and the international livestock trade have all potentially contributed toward the spread of Hyalomma ticksâ€Â""the primary vector for CCHFV. Expanding endemic zones, widespread morbidity and significant mortality make CCHFV an acute threat to public health and thus is listed as a NIAID Category A priority pathogen. The viral genome encodes a glycoprotein precursor that is processed into two structural glycoproteinsâ€Â""Gn and Gcâ€Â""and two secreted glycoproteinsâ€Â""a mucin-like domain and GP38. Protective antibodies have been isolated that target Gc or GP38, suggesting that these two proteins should be given priority for vaccine development. Here we propose to engineer Gc- and GP38-based immunogens that focus the immune response onto broadly conserved epitopes that are capable of eliciting protective antibody responses. To accomplish our goal, we will structurally characterize CCHFV glycoproteins and their interactions with human-derived antibodies, rationally engineer vaccine antigens based in part on the structural information, and characterize the immune responses elicited by these antigens in animal models. These results will be used to guide further improvements of the immunogens, including display on self-assembling multi-valent nanoparticles, and the most promising candidates will be evaluated in a lethal murine model of CCHFV challenge. Given our expertise, unique reagents, and preliminary data, we are confident that we can deliver a state-of-the-art subunit vaccine candidate with the potential to induce cross-reactive protective antibodies, thereby satisfying an unmet need against this NIAID Category A tick-borne pathogen.",,2025,University Of Texas At Austin,428507,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +P21714,5R41AI157527-02,A Novel Broad-spectrum Antiviral Agent,"Summary Accelerating emergence and re-emergence of a wide array of viral epidemics has been a deadly feature of the 21st century. Potent or even effective therapies are rarely available to combat these diseases, and in general, the world remains unprepared to manage future outbreaks. The most recent outbreak of the Ebola virus resulted in over 11,000 fatalities, more than 20,000 orphans, and economic costs of >$32B (Worldbank), and instilled varying levels of fear in many more. But Ebola is not unique; in 2003 the global economic loss from the SARS virus was ~$40B (WHO). In 2017, there were travel and pregnancy restrictions within the Americas due to the Zika virus and its high correlation with the surge in the incidences of infant microcephaly. Currently, the world is experiencing unprecedented hardship from the life-threatening COVID-19 (SAR2-CoV-2) pandemic, which has already resulted in over 150,000 deaths worldwide, and for which there is no effective therapy or vaccine. Unfortunately, this is neither the first nor the last time the world is expected to be in this plight, unless a broadly acting first-line drug is available for rapid deployment. These outbreaks all resulted from RNA viruses, which remain a major unaddressed disease class. Arenaviruses (e.g. Lassa fever virus and Junin virus), coronaviruses (including SARS-COV-1, SARS-CoV-2, and MERS), and filoviruses (e.g. Ebola and Marburg viruses) are enveloped RNA viruses that cause severe and often fatal human diseases. Despite the global impact and toll on human lives, there are no effective treatment options or FDA-approved vaccines available to combat these devastating infections and they are accordingly classified as NIAID Priority Pathogens and are also on the select agent list of potential bioterrorism threats. This proposal seeks to address this highly significant, unmet clinical need by developing a broad spectrum antiviral agent (BSAA) that targets a fundamental host protein that is commonly subverted by multiple pathogenic virus families but is not essential for the host. In particular, we propose to target the human ER-Golgi intermediate compartment protein 53 kDa protein (ERGIC-53), a mannose-specific lectin that functions as an intracellular cargo receptor to facilitate the anterograde transport of selected cellular glycoprotein ligands in the early exocytic pathway. We have shown that ERGIC-53 is critically required for the propagation of arenaviruses, coronaviruses, and filoviruses. In particular, ERGIC-53 i) associates with the envelope glycoproteins encoded by these viruses as well as orthomyxoviruses and hantaviruses, ii) traffics to sites of virus budding, and iii) is incorporated into viral particles. In the absence of ERGIC-53, viral particles containing the normal array and quantity of viral structural proteins and genome are formed but are no longer infectious. Specifically, virions lacking ERGIC-53 are defective in their ability to attach to host cells. We have mapped the minimal domain within ERGIC-53 that is required for controlling virion infectivity and shown that extracellular targeting of this region potently neutralizes the infectivity of multiple pathogenic RNA viruses. Herein, we have presented strong scientific rationale for targeting ERGIC-53 and proof of concept data that extracellular targeting of ERGIC-53 is an effective antiviral target. Our development plan includes collaborating with Lake Pharma, a company with a proven track record in antibody generation technology. The successful development of potent antiviral monoclonal antibodies targeting ERGIC-53, would be groundbreaking in the treatment of viral outbreaks. Due to its broad spectrum activity and the expected safety of target modulation, ERGIC-53 targeting has the potential to be a first-line strategy against many RNA viruses.",,2022,"CELDARA MEDICAL, LLC",290738,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21715,1R43CK000697-01A1,"PA21259, SBIR, Phase I, Aptamer-upconverting nanocrystal conjugate lateral flow assay for immediate Ebola virus detection","Ebola virus, listed under Category A priority pathogen by NIAID, is one of the most deadly viruses with a mortality rate of 50-90% in humans. Early detection of Ebola virus infection can save thousands of lives by enabling isolation of infected individuals from susceptible ones. Currently the available diagnoses can only detect Ebola infection after the onset of symptoms which typically takes place within 14-21 days of viral exposure. This time lag in diagnosis facilitates viral outbreak and is an obstacle for infection control efforts. Additionally, the available point of care (POC) diagnosis gives qualitative results, visually confirmed by two independent readers and in case of disagreement a third reader is required. Cold chain support is also required for their transport and storage which is often difficult to arrange in remote areas where the viral outbreaks occur. Therefore, the limitations of the current diagnosis costs valuable lives and calls for advancement in the method of diagnosis. Our goal is to develop a user-friendly and cost-effective portable device for reliable immediate detection of Ebola viruses at POC. For that purpose, we have chosen the Ebola virus soluble glycoprotein (sGP) as the biomarker, which is secreted in the host blood at a concentration of 137 ng/ml within 3 days of exposure. The innovation of our proposal lies in the combination of aptamer technology with up-converting phosphors (UCPs) to develop a lateral flow (LF) assay sensor. Aptamers are nucleic acids that bind their targets avidly and specifically and are selected in vitro by Systematic Evolution of Ligands by EXponential enrichment (SELEX). For biosensor development, aptamers have many advantages over antibodies, including their smaller size, ready and inexpensive synthesis, reliable production, amenability to chemical synthesis and modifications, adaptability to a broad range of assay format, and long-term stability at room temperature. Conjugation of aptamers with UCPs is also expected to lower background fluorescence signal, which will enhance the sensitivity of the proposed LF assay. In phase I, we will optimize the sensor resolution and sensitivity, deploying our developed DNA aptamers against sGP in human serum. If successful, our prototype will have an immense impact on the current diagnostic research by combining the robustness of aptamers with the sensitivity of UCPs and the operational ease of LF assays. Specifically, we will improve existing diagnostic method by offering: 1. Immediate detection: the presence of Ebola will be detected from the infected serum within 3 days of exposure in contrast to the current detection around 14-21 days of exposure. 2. Longer shelf life will be imparted without the need of cold chain support by the robustness of aptamers and 3: Low cost will also be imparted as the aptamers are more cost effective and more reliably produced compared to antibodies.",,2024,"APTALOGIC, INC",264271,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P21716,1K08EB033409-01,Development of Optofluidic Resonators for Filoviral Detection,"Project Summary/Abstract This proposal describes a 4-year career development plan for the PI, Dr. Abraham J. Qavi, MD, PhD, with the goal of preparing him for an independent research career as a physician scientist. This plan includes expand training opportunities and a pathway to an independent career that includes the development and implementation of sensor technologies and its application towards filoviruses, namely Ebola. The PI graduated with degrees in Biochemistry & Molecular Biology and Chemistry from the University of California, Irvine. He then enrolled in the Medical Scholars Program at the University of Illinois at Urbana-Champaign, where he earned his MD and PhD in Chemistry. Dr. Qavi continued his medical training as part of the Clinical Pathology Physician Scientist Training Program at Washington University in St. Louis and the Barnes-Jewish Hospital consortium. During his residency elective time, he began research in the laboratory of Dr. Lan Yang, who will serve as his co-mentor together with Dr. Amarasinghe. Dr. Yang is the Edwin H. and Florence G. Skinner Professor of Electrical & Systems Engineering, and an internationally renowned researcher in photonics. In 2019, Dr. Qavi added an additional training component under the co-mentorship with Dr. Gaya Amarasinghe, Professor of Pathology & Immunology, to expand the application of his previously developed sensor technology to infectious disease reach. The goal of this study is the development of a rapid, multiplexed optofluidic sensor platform for the rapid detection of pathogens, with an initial focus on Ebola. Filoviruses, such as Ebola, are among the most lethal human pathogens, with high case fatality rates during outbreaks. Critical in the identification and management of outbreaks are robust detection methods that can be implemented rapidly and sensitively. To address this critical need, Whispering Gallery Mode (WGM) sensors will be leveraged. WGM devices are a class of optical sensors in which light is confined within a micron-scale volume. These devices have incredibly high sensitivity, small sensor footprint, ease of integration with conventional electronics, and low fabrication costs. Microbubble resonators (MBRs), a subclass of WGM sensors, offer the advantages of conventional WGM devices while enabling coupling of optical and the fluidic components into a single component. The goal of this proposal is the use of an optofluidic sensor platform based on MBRs for the rapid, multiplexed detection of Ebola. The workflow and advancements, including MBR development, engineered antibodies, biophysical validation and multiplexing, will provide the framework to extend the work beyond the initial goals and promote facile transition to an independent career for Dr. Qavi.",,2023,Washington University,73072,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P21717,1G20AI174669-01,Pandemic Preparedness: Biocontainment Facility Upgrade and Integration at UTMB/Galveston National Laboratory,"PROJECT SUMMARY/ABSTRACT Toward maintaining and improving pandemic preparedness, we propose value-added facility upgrades that better integrate the high-containment communities at the University of Texas Medical Branch (UTMB), Galveston. UTMB laboratories integrate operations through joint-facility management, usage, and collaborations that include educating the next generation of research scientists and medical staff. The UTMB community contains the Robert E. Shope Laboratory (Shope)â€Â""the first full-sized BSL-4 facility within a university in the United States, a structurally separate high-containment Galveston National Laboratory (GNL), and BSL3 laboratories of Mary Moody Northen Pavilion (MMNP). Each facility supports multiple experienced, published, and governmentally-funded investigators researching pathogens with pandemic potential, as well as facilitating biomedical research of vaccines and therapeutics. Our corpus of researchers includes 31 experts in one or more of six out of the seven RNA viruses of focus by NIAID toward Pandemic Preparedness. The requested financial support will enhance facility capabilities and security within an integrated system of services and operational functions that support the mandate of the GNL within the UTMB high-containment community. We propose to enhance integration of systems to provide a comprehensive protection of all UTMB high-containment facilities against cyberattack, while improving workflow, biosafety, biosecurity, and training capacities through modernization of specific antiquated high-containment areas that are also essential to pandemic responsivity. Of priority is to upgrade equipment and supportive infrastructure utilized in high-containment RNA viral research reaching “end-of-life” (EOL) or “end-of-service” (EOS), prior to experiencing difficulties procuring parts or having stoppage resulting in lost time, funds, and mitigating preparedness. Additionally, we will remedy specific infrastructural shortcomings to improve facility operations. Furthermore, as a leader in teaching the future investigators of high-consequence pathogens, the GNL proposes to upgrade a training area to better reflect the actual BSL4 environment. We will meet these goals through three Aims: Aim 1: Integrate cybersecurity systems under the GNL isolated protection, while modernizing safety and security of virtual and physical structures of UTMB high-containment facilities. Aim 2: Modernize facility and equipment of integrated usage among UTMB’s research community directly in support of BSL3 and BSL4 RNA research of viruses with high pandemic or weaponization potential. Aim 3: Implement pandemic preparedness toward effective future strategic response capacity. Ultimately, modernizations and integrations of systems, operations, and training will better position UTMB to contribute as a global research leader in discovery and development of solutions against high- consequence pathogens. This proposal is framed to provide enhanced security and capacities to further support our roles as collaborator, reference center and repository, institutional model, and trainer toward strategic implementation of a global pandemic preparedness.",,2024,University Of Texas Med Br Galveston,7131815,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P21718,5R41AI152745-02,Whispering Gallery Mode Devices for the Rapid Detection of Pan-Filoviruses,"Project Summary Filoviruses, including the Ebola viruses, Marburg viruses, and Cueva virus, are a class of pathogens with enormous health implications. Filoviruses have been implicated in numerous outbreaks in Africa, including the ongoing outbreak in the Democratic Republic of Congo (DRC), potential risk as an agent of bioterrorism, and the potential risk of transmission to non-endemic countries such as the United States. Critical in both the management of outbreaks as well as the treatment of infected patients are specific and rapid diagnostic tests. Despite the critical health risk posed by these pathogens, current diagnostic techniques utilizing PCR and ELISAs have significant limitations, including the need for centralized laboratories, cold-chain custody, and limited diagnostic ability in the early stages of infection. This proposal seeks to fill this gap and leverage a highly sensitive class of optical sensors, whispering gallery mode (WGM) devices, for the rapid detection of filovirus glycoproteins (GP) and the ebolavirus soluble glycoprotein (sGP), two highly sensitive biomarkers for filoviruses. WGM sensors are a unique class of optical devices in which light is confined to a small volume, therefore leading to an enormous enhancement in signal response. In addition to their sensitivity, these devices also offer the advantages of inexpensive and scalable fabrication costs, the ability to be integrated with conventional electronics, and the potential for multiplexed measurements. In combination with these devices will be antibodies against filovirus GP and sGP, the latter an enormously powerful sentinel biomarker that is positive hours to days before presentation of symptoms in infected individuals. This academic-industry partnership will develop a rapid and sensitive diagnostic test for filovirus GP and sGP, and subsequently lay the foundation for the developing this technology into a powerful, field-deployable device for filovirus detection.",,2023,"INTEGRATED BIOTHERAPEUTICS, INC.",291845,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21719,5R21EY031465-02,Predicted Role of Ebola VP40-Host Interactions in Ocular Pathology and Persistence,"Ebola virus (EBOV) can cross cellular barriers, establish persistence, and re-emerge in survivors months later in the eye, central nervous system, and semen, leading to long term pathology and sequelae. Indeed, a wide spectrum of ocular complications, including hemorrhages, blindness, and uveitis, have been reported following both acute EBOV infection and during long-term convalescent stages. The mechanisms by which filoviruses enter, persist, and re-emerge in the eye remain unknown. Retinal pigment epithelial (RPE) cells are permissive for EBOV infection and are thought to serve as the intraocular reservoir for persistence and spread of EBOV. Based on our preliminary data, we hypothesize that EBOV VP40 (eVP40) contributes to the spread of EBOV to the human eye by interacting with tight junctional (TJ) complex proteins in the RPE and/or corneal endothelium, thereby weakening these barriers to facilitate virus infection and spread during acute infection, as well as during re-emergence from a persistent state. Specifically, we have shown that the PPxY motif conserved in filovirus VP40 proteins can interact with select host WW-domain bearing proteins that are involved in maintaining and regulating the physical and functional integrity of cellular TJs. These VP40 interactors include MAGI3, a member of the MAGUK superfamily of proteins, that functions as an adaptor/scaffolding protein to maintain junction integrity and barrier function as well as YAP and TAZ; paralogues and downstream effectors of the Hippo signaling pathway that regulate genes involved in cell proliferation and migration and junctional integrity. The interaction of YAP/TAZ and MAGI3 with the PPxY motifs of filovirus VP40 is particularly intriguing, as these host proteins are also regulated by the binding of their WW-domains to the N-terminal PPxY motifs of the host protein AMOT (Angiomotin). Indeed, Amot negatively regulates YAP activity by binding and sequestering YAP at TJs, and promotes TJ assembly and integrity by interacting with the MAGI family of scaffolding proteins. Since Amot, via its PPxY motifs, appears to be a “master regulator” of TJ formation and function, we hypothesize that the PPxY motifs of filovirus VP40 may compete with those of Amot to disrupt TJ formation and function in virus infected cells, thereby enhancing cellular permeability and virus spread. In this high risk, high impact proposal, we will use a powerful and innovative eye-on-a-chip technology to provide a human cell-based model system with an unprecedented level of physiological realism to investigate: 1) the role of VP40 in altering the most essential barriers of the human eye, and 2) to determine whether our previously validated PPxY inhibitors not only can block VP40-mediated egress and spread, but also prevent VP40-mediated disruption of TJ barriers and disease progression in these eye models. This exploratory and innovative approach will provide new fundamental insights into the molecular mechanisms of filoviral-host interactions in the human eye that may contribute to transmission and pathogenesis of these deadly viruses, and may identify a new therapeutic strategy to treat filovirus infections in these ocular tissues.",,2023,University Of Pennsylvania,196879,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +P21720,1F31AI157079-01,Leveraging protein dynamics to drug filovirus protein-nucleic acid interactions using simulations and experiments,"Project Summary Many proteins are classified as ‘undruggable,’ especially those that engage in protein-protein and protein- nucleic acid interactions as they interact with their binding partners through flat interfaces. This is particularly true in the case of many viral proteins that interact with host factors and viral nucleic acids and lack enzymatic activity. In the highly lethal filovirus family one protein, viral protein 35 (VP35) is primarily responsible for the viruses’ immune evasion. In this family the ebolavirus is the most fatal with a case fatality rate at 66% in recent outbreaks. Thus, there is a great need for discovering new therapeutic targets in this family of viruses. Although proteins are known to be dynamic, only recently has considering protein dynamics for drug design become tractable through advances in molecular dynamics methods. As such, discovering ‘cryptic’ pockets that are absent in available structures but open due to protein dynamics could provide new druggable sites. Here, I propose integrating atomically-detailed simulations, biophysical, and cellular experiments to understand the cryptic pocket in viral protein 35 (VP35) from the highly lethal filoviruses. VP35 plays multiple essential roles in these viruses’ replication cycles, including binding the viral RNA genome to block hosts’ innate immunity and acting as a polymerase co-factor. However, available crystal structures of VP35 lack appealing pockets for drug discovery and the protein has so far remained undruggable. We recently have applied adaptive sampling simulations to preferentially sample conformations with large pocket volumes. This revealed a potentially druggable cryptic pocket. While the pocket does not directly coincide with the crucial interface for binding RNA, we have shown that the pocket can allosterically modulate RNA binding and is a good drug target. To further test this, I will use a thiol labeling experiment to directly test for this cryptic pocket in VP35 homologs. Then, to determine if this cryptic pocket is allosterically coupled to function, I will test if stabilizing the open form allosterically disrupts RNA binding using a fluorescence anisotropy assay. I will then screen for small-molecule inhibitors of RNA binding that bind to the cryptic pocket and confirm this by X-ray crystallography and mutational tests. Finally, I will assess the effect of stabilizing the open pocket on VP35’s interferon antagonism, and viral replication activities using an in-vitro ATPase assay and cellular minigenome assay. Successful completion of these experiments will further the National Institute of General Medical Sciences’ mission to increase our understanding of biological processes for laying the foundation of advancing disease treatments. These results will demonstrate the power of fusing simulations and experiments to characterize hidden conformations and dynamics, uncovering cryptic pockets and allostery that present new therapeutic opportunities.",,2022,Washington University,31970,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21721,5R44AI150263-02,A modular platform for infectious disease surveillance at point-of-need.,"ABSTRACT We propose to develop a point-of-need system for differential molecular identification of filoviruses from syndromically similar infections. Our goal is to enable rapid, sensitive, and specific identification of quarantinable infections to reduce nosocomial risk and improve outbreak response. The platform will simultaneously test 12 genomic markers at the genus and strain level using a modular microfluidic design that allows for rapid panel update and expansion. In Phase I we will develop an assay for pan-filovirus (pFi), followed by expansion of the panel and system integration in Phase II. The expanded panel will add pan-flavivirus (pFa) and pan-Plasmodium (pPa) detection as well as strain-specific targets for Ebola, Marburg, Dengue, Yellow Fever, and Malaria. Strain specific tests will enable better patient triage/treatment during an outbreak and improve disease surveillance in non-outbreak settings. The panel will require a 50 μL sample of whole blood and will achieve highly specific detection in < 30 minutes. To achieve this goal, we will combine Redbud Labs’ expertise in microfluidics and systems with the diagnostic development expertise of the Diagnostics Program at PATH (Seattle, WA), and the VHF testing/processing capabilities of the Connor Lab at Boston University (part of the BSL-4 facilities at NEIDL).",,2022,"REDBUD LABS, INC.",291649,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21722,1R21AI159703-01,Ebola virus infection of the female reproductive system,"SUMMARY/ABSTRACT Ebola virus (family Filoviridae) is the causative agent of Ebola virus disease (EVD), which is characterized by hemorrhagic fever in humans, reaching high mortality rates (≥40%). Sexual transmission of Ebola virus from a male survivor to a woman was first documented during the large 2014-2016 West African outbreak. Then this route of infection was reported to be likely responsible for multiple EBOV outbreak flare-ups between 2015 and 2016. Infectivity of the semen of survivors was later documented for at least 179 days after the onset of disease. Mathematical modelling of the contribution of sexual behavior in virus transmission during that same outbreak showed that abstinence, along with infectious patient isolation, could stop an outbreak. As of June 2nd, 2020, the on-going EBOV outbreak in the Democratic Republic of the Congo describes 3463 cases with 2280 deaths, and there are no data available as to which route of infection is primarily responsible of transmission and the situational awareness of survivors to spread EVD. Recently, our group demonstrated that human vaginal epithelial cells are susceptible to infection with Ebola virus, support productive viral replication resulting in a robust proinflammatory response. Furthermore, we evaluated the antiviral efficacy of the vaginal Polyphenylene Carboxymethylene (PPCM) microbicide as a countermeasure and could show suppression of virus replication and virus-induced inflammatory response in these cells. Altogether, these facts support the critical need to develop new experimental models for this route of infection and therapeutics preventing virus transmission during unprotected sexual intercourse. Our long-term goal is to better understand sexual transmission of Ebola virus, and to identify prophylactic methods other than condoms. The objective in this proposal is to investigate Ebola virus pathogenesis in women following sexual transmission using a relevant in-vitro model of the human female reproductive system as well as a susceptible mouse model. Our central hypothesis is that the human female reproductive system is susceptible to Ebola virus infection leading to atypical clinical manifestations of EVD and laboratory characteristics compared to those observed after infection by Ebola virus using other more documented routes of infection. To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Characterize Ebola virus infection and inflammation in-vitro using a model of the human vaginal epithelium cultured at air-liquid interface, (2) Establish an in-vivo model of Ebola Virus Disease (EVD) following intravaginal virus challenge, and (3) Evaluate the protective antiviral efficacy of PPCM in-vitro and in-vivo. The proposed studies will develop novel models for research of filovirus pathogenicity and further develop PPCM as a microbicide for Ebola virus infection.",,2023,University Of Texas Med Br Galveston,197500,Human Populations | Viruses,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Prophylactic use of treatments",2021 +P21723,5R21AI153475-02,A Transgenic Mouse Model to Study Ebolaviruses and other Filoviruses,"PROJECT SUMMARY Ebola viruses and other members of the filovirus family cause severe and often lethal infections. While some progress has been made in regards to the development of experimental countermeasures and insights into the highly pathogenic nature of these viruses, there are still many more unanswered questions, and further advancement is needed towards the development of pan-filovirus therapeutic agents and vaccines. A significant hurdle to research on filoviruses is the accessibility and cost associated with high-containment, biosafety level- 4 laboratories. To partially alleviate this issue, we previously established a replication-defective Ebola virus based on the Zaire ebolavirus (EBOV) genome. This virus, which lacks the essential viral gene VP30 (termed EBOVÃŽÂ""VP30), is biologically inert and safe to use outside of highly specialized BSL-4 containment. In engineered cell lines that stably express EBOV VP30, the virus becomes replication-competent; thus it is a perfect EBOV surrogate for in vitro research given that EBOVÃŽÂ""VP30 resembles authentic virus in its life cycle, morphology, protein composition, and growth kinetics. After extensive safety testing both in cell culture and in animal models, the CDC and the Office of Science Policy at the NIH classified EBOVÃŽÂ""VP30 as a BSL-2 agent and removed the virus from Select Agent regulations. Since then, this in vitro system to study EBOV has been requested by and distributed to several other research laboratories. The next step to advance the EBOVÃŽÂ""VP30 system is to develop an EBOV VP30 transgenic animal model to support virus replication. Previously, we generated a transgenic mouse line that expressed EBOV VP30 under the control of the chicken beta-actin promoter (CAG). Although we were able to detect VP30 mRNA in key organs, such as the liver, and functional VP30 protein in cells, such as fibroblasts, we were unable to detect VP30 mRNA and functional protein in monocyte-derived macrophages, the first target of EBOV infection and a cell type essential for virus dissemination throughout the body. Here, we propose to generate a new transgenic mouse line with EBOV VP30 expression under the control of the CD45 promoter, a promoter specific for expression in hematopoietic cells, including monocytes, macrophages, and dendritic cells. Once we confirm the expression and function of VP30 in these cell types, particularly macrophages, we will cross our two different VP30 transgenic lines (CAG and CD45) to generate a double knock-in transgenic mouse line. Once established, we will infect these transgenic mice with mouse-adapted EBOVÃŽÂ""VP30 and characterize the phenotype. We will also generate chimeric versions of EBOVÃŽÂ""VP30 with glycoproteins from other filoviruses and examine the phenotype of these chimeric viruses in the transgenic mice. After safety testing, this new small animal model will be an ideal in vivo surrogate for the authentic mouse model for EBOV infection. For the first time, a transgenic mouse model will be available that can be used efficiently and safely outside of BSL-4 containment to examine EBOV pathogenesis and accelerate the development and evaluation of countermeasures.",,2023,University Of Wisconsin-Madison,194271,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2020 +P21724,5R21AI152200-02,Engineering pathogen triggered biomineralization to enable a new generation of point-of-care tests,"ABSTRACT Biomineralization is a coalescence of organic (soft) and inorganic (hard) chemistries where proteins or peptides borne on a close-knit macromolecular scaffold serve as nucleation sites for salts to precipitate from solution and grow into crystals. When these proteins or peptide motifs are free in solution phase at low concentrations, biomineralization does not occur. We aim to harness this concentration dependent phenomenon to formulate a new generation of pathogen specific assays. Biomineralizing motifs will be fused to antibodies specific to macromolecular scaffolds of pathogens, so that the presence of pathogen will cluster the fusions, concentrating them to trigger crystal formation. The approach requires no washing steps and should give a visible readout in this feasibility study for an exploratory point-of-care assay. We will first isolate protein motifs capable of driving the formation of physiological buffer salt crystals from solutions. We will then employ Filovirus preparations and pre-existing antibodies against polyvalent viral cores to assess biomineralization potential of motif-antibody fusions and establish limits of detection (LOD) for Ebola and Marburg viruses to benchmark our system. Finally, we will engineer mutants of the motifs to understand drivers of biomineralization, accelerating the process, reducing assay times and lowering LOD. While initially meant as a point-of-care assay feasibility study, the process should also be addressable by conductivity measurements and imaging for biosensing applications. If successful, future developments could also include retuning the process to operate against adjacent nucleic acid sequence targets by fusing the biomineralizing motifs to oligonucleotide probes. Convenient and inexpensive diagnostics that don’t require vast infrastructure investment are desperately needed in the field, especially for emerging zoonoses in resource limited geographies. Our feasibility study will show whether biomineralization can contribute to solving this problem and offer a paradigm shifting parallel track for further development to help safeguard human health.",,2024,TEXAS BIOMEDICAL RESEARCH INSTITUTE,247500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21725,5R01AI156866-02,Spillover of Ebola and other filoviruses at ecological boundaries,"More than half of all infectious disease outbreaks across the globe are zoonotic, involving pathogen spillover from animal reservoirs to humans. Ebola and other filoviruses rank among the most deadly zoonoses. Recent large outbreaks with mortality in the thousands both in humans and wildlife underscore the pressing need to better understand the factors promoting filovirus spillover. Although spillover is commonly defined as a pathogen crossing species boundaries, there are relatively few empirical studies or modeling frameworks that explicitly consider ecological boundaries across which spillover occurs. Crossing ecological boundaries involves processes that occur at many levels of organization: physiological processes at the individual level, interspecies interactions between individuals at the population level, interactions between populations of different species at the community level, and interactions between ecological communities within landscapes. Processes accelerating spillover often involve human activities such as habitat encroachment and land conversion, which are themselves ultimately driven by socioeconomic factors. In the context of Ebola and other filoviruses in Africa, we will develop the data sets, theoretical models and statistical tools needed for a general descriptive and predictive framework for spillover at ecological boundaries. Our project will follow an iterative design where results from mechanistic models are used to refine patterns that we test for empirically, and statistical models of large-scale data allow us to more realistically parameterize mechanistic models. Our work will test the generality of specific theories that so far have been applied only to a limited number of study systems. For example, ours will be among the first attempts to test the influence of Schmalhausen’s law -- an evolutionary theory that may explain the tendency for large outbreaks to occur at the edges of species ranges or during unusual weather conditions and which to date has primarily been investigated in the context of malaria -- in pathogens that rely on direct transmission. This work will demonstrate how new methods can provide unifying insight into patterns in critically important disease transmission systems and will enhance our ability to predict spillover of both filoviruses and many other zoonotic pathogens. Note that no human subjects, biohazards, or select agents will be involved in this project.",,2021,University Of Georgia,77018,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21726,7R01AI125453-06,Small Molecule Inhibitors of Ebola Virus Polymerase Function,"Project Summary Filoviruses, which include the ebolaviruses and marburgviruses, are non-segmented, negative-sense RNA viruses (NNSVs) that cause severe human disease. These viruses are of concern as emerging pathogens and as potential bioterrorism threats. Their importance and public health impact are reinforced by the West Africa epidemic that began in winter of 2014 and has resulted in more than 11,000 deaths and the export of Ebola virus disease to the U.S., the U.K. and Europe. Although the past year has seen progress toward development of effective vaccines and treatments, current prophylactic and treatment options remain limited. Particularly lacking are effective small molecule inhibitors. Complicating development of anti-filovirus drugs is the biosafety level 4 (BSL4) containment needed to work with live filoviruses, which is only available at a few locations worldwide. With substantial restrictions on the number of investigators who have access to such facilities, antiviral testing against infectious virus in a high throughput setting is problematic. An alternate approach is to develop assays of specific viral functions that can be assessed without generation of infectious materials. The viral RNA-dependent RNA polymerase (RDRP) complex is a particularly promising candidate. The complex consists of the viral nucleoprotein (NP), viral protein of 35KDa (VP35), VP30 and the large protein (L) which is the enzymatic component of the complex and the only enzyme encoded by the virus. The RDRP complex is required for viral mRNA expression and viral genome replication and is therefore essential for virus growth. Inhibition of the RDRP complex would arrest virus replication. The Basler and Shaw laboratories collaborated to optimize for 384-well high throughput screening a minigenome assay in which a functional EBOV RDRP complex is reconstituted by transfection of plasmids that express its four components into mammalian cells. RDRP activity is measured through the co-expression of a model viral RNA (minigenome RNA) that encodes a reporter gene flanked by the appropriate virus-derived cis-acting regulatory sequences. This system has been successfully transferred to collaborator Sumit Chanda at Sanford Burnham Prebys Medical Discovery Institute where a 6,400 compound pilot screen was performed. This screen yielded hits which were carried through to BSL4 testing by Robert Davey at Texas Biomedical Research Institute and demonstrated to inhibit Ebola virus replication. We propose to exploit this assay and this drug discovery pipeline to identify novel small molecule inhibitors of the Ebola virus polymerase. We will also develop additional HTS-compatible minigenome assays based on other filoviruses associated with deadly human disease, including Bundibugyo ebolavirus and Marburg virus, to identify and prioritize hits with pan-filovirus activity. A combination of minigenome assay and filovirus BSL4 experiments will define mechanisms of action, and together with initial SAR studies will prioritize hits for future development. The completion of these studies will significantly expand the number of potential therapeutic small molecules and provide significant insight into inhibition of the filovirus RDRP complex.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,770311,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +P21727,1U01AI160397-01,"Defining molecular mechanisms of combination adjuvants: a systems immunology, transcriptomics and imaging approach","PROJECT SUMMARY/ABSTRACT In this proposal we will define molecular and cellular mechanisms of different combinations of known adjuvant components MPLA (a TL4 agonist), CpG (a TLR9 agonist), agonists of cGAS-STING and NOD1/2 pathways, and a squalene-in-water emulsion (AddaVAXâÂ""¢). Our overall Aim is to provide a detailed analysis of every combination of these using high throughput in vitro and in vivo assays, followed an in-depth analysis of two combination adjuvants using live cell imaging and single-cell mRNA sequencing of draining lymph nodes after vaccination. Initially, 96-well based in vitro assays of innate and adaptive immune system activation will be used to profile different adjuvants components, both individually, and in different combinations and concentrations. These assays will comprise: 1) activation of TLR, NOD and STING signaling pathways using primary dendritic cells (DCs), T and B cells from reporter transgenic mice; 2) in vitro activation of naïve B cells to monitor their differentiation into plasma cells and class switching. We anticipate some of the adjuvant combinations will have synergistic effects that differ from the sum of the effects when used individually. Next, based on performance in vitro a subset of combination adjuvants and their individual components will be evaluated as adjuvants for model vaccine antigens (influenza hemagglutinin H1, filovirus (EBOV) glycoprotein and SARS-CoV-2 spike) in vivo in mice. Immunogenicity metrics will comprise: 1) antibody dynamics and durability, isotype, avidity and breadth of cross-reactivity using protein microarrays; 2) flow cytometry of antigen-specific B cells to assess differentiation and cross-reactivity; 3) T cell recall assays to define Th1/Th2/Th17 cytokine profiles; 4) neutralization by sera of live influenza, SARS-CoV-2 and VSV-pseudotyped with EBOV glycoprotein. This will provide a comprehensive cellular and molecular profile associated with each combination adjuvant. Two combination adjuvants (and their individual components for comparison) will be selected for a deep analysis using: 1) transgenic mice that allow Ca2+ fluxes in live CD4 T and B cells and DCs to be visualized using 2- photon microscopy. Combined with techniques of whole tissue imaging, we will monitor adjuvant-driven T cell and DC mobilization, motility and interactions in live draining lymph nodes; 2) using single-cell RNAseq technology (10x Genomics Inc) of cells in draining lymph nodes, we will define cell composition and phenotype, cellular interactions and spatial organization. We will perform a deep analysis in Year 1 on the combination adjuvant CpG/MPLA + AddaVAX (TLR9 and TLR4 agonists in a squalene-in-water emulsion) since we have already shown this is a powerful combination adjuvant. A second combination adjuvant will be selected for deep analysis based on data generated in the in vitro and in vivo assays described herein. Together these complementary deep approaches will provide an unprecedented level of molecular and cellular detail of two highly effective combination adjuvants. Overall, we anticipate these data will help guide the future design of vaccines where the immune response required can be tuned according to the particular pathogen in question.",,2025,University Of California-Irvine,610134,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Orthomyxoviridae,H1,Unspecified,,,,,,,COVID-19 | Ebola virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2021 +P21728,75N93020C00040-P00001-9999-1,Advanced Development of Vaccines for Filoviruses ,"To support the advanced development of multivalent vaccine candidates for filoviruses and Lassa Fever. This contract aims to formulate a multivalent vaccine that provides protection against several pathogens, including Ebola virus, Marburg virus and Lassa Fever. It may support cGMP manufacture of a stable lyophilized vaccine formulation and preparation and submission of an IND to support eventual clinical evaluation.",,2026,AURO VACCINES LLC,986612,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P21729,1R21AI151717-01A1,The role of macrophage podosomes in Ebola virus pathogenesis,"PROJECT SUMMARY Ebola virus (EBOV) is an emerging, highly pathogenic virus associated with increasingly more frequent outbreaks of hemorrhagic disease in human populations. Approved countermeasures to prevent or treat EBOV disease are currently limited. Macrophages are the initial cells targeted by EBOV, and yet, little is known about the exact nature of EBOV-macrophage surface interactions and subsequent uptake into the cell. Due to their migratory properties, macrophages are also believed to rapidly disseminate the virus to distant tissues and organs despite the lack of experimental evidence. We have preliminary data showing that EBOV depends on podosomes, mechanosensitive adhesive structures used by macrophages to migrate through tissues and sample antigens, to enter macrophages. The data also shows that EBOV replication increases macrophage locomotion through a fibrillar 3D matrix and reduces podosome number, suggesting that the virus actively transforms infiltration of tissues by these cells. This proposal aims to examine the interactions between EBOV and podosomes. In Aim 1, we will determine whether podosomes serve as ports for EBOV entry into human macrophages. In Aim 2, we will characterize migratory and invasive properties of macrophages challenged with EBOV. In Aim 3, we will assess host resistance to systemic infection with EBOV in a mouse model of EBOV disease devoid of functional macrophages. Our findings will establish a new model of interactions between EBOV and macrophages, laying the groundwork for further investigations into pathogenesis of filoviruses. Importantly, these discoveries may lead to new areas of development of novel countermeasures targeting EBOV and related viruses.",,2022,TEXAS BIOMEDICAL RESEARCH INSTITUTE,297000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21730,5R21AI144215-02,CD40 regulation of acute virus infection,"CD40 signaling is well established to enhance development and maintenance of adaptive immunity. However, the role of CD40 signaling during innate immune responses is more poorly studied and an important role for CD40 signaling in rapid control of acute virus infections is not currently appreciated. Here, we provide strong preliminary findings that CD40 signaling is critical for early stimulation of innate immune pathways in peritoneal macrophages, resulting in control of acute viral infection. In these proposed studies, we will use both Ebola virus (EBOV) and a BSL2 model virus of EBOV to identify the CD40+ cellular compartment(s) required for protection and understand the breadth of cell populations that use CD40 signaling to control EBOV infection. Elucidation of these cell populations will elucidate targeted approaches that can lead to therapeutic interventions.",,2023,University Of Iowa,206611,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P21731,7R01AI156866-03,Spillover of Ebola and other filoviruses at ecological boundaries,"More than half of all infectious disease outbreaks across the globe are zoonotic, involving pathogen spillover from animal reservoirs to humans. Ebola and other filoviruses rank among the most deadly zoonoses. Recent large outbreaks with mortality in the thousands both in humans and wildlife underscore the pressing need to better understand the factors promoting filovirus spillover. Although spillover is commonly defined as a pathogen crossing species boundaries, there are relatively few empirical studies or modeling frameworks that explicitly consider ecological boundaries across which spillover occurs. Crossing ecological boundaries involves processes that occur at many levels of organization: physiological processes at the individual level, interspecies interactions between individuals at the population level, interactions between populations of different species at the community level, and interactions between ecological communities within landscapes. Processes accelerating spillover often involve human activities such as habitat encroachment and land conversion, which are themselves ultimately driven by socioeconomic factors. In the context of Ebola and other filoviruses in Africa, we will develop the data sets, theoretical models and statistical tools needed for a general descriptive and predictive framework for spillover at ecological boundaries. Our project will follow an iterative design where results from mechanistic models are used to refine patterns that we test for empirically, and statistical models of large-scale data allow us to more realistically parameterize mechanistic models. Our work will test the generality of specific theories that so far have been applied only to a limited number of study systems. For example, ours will be among the first attempts to test the influence of Schmalhausen’s law -- an evolutionary theory that may explain the tendency for large outbreaks to occur at the edges of species ranges or during unusual weather conditions and which to date has primarily been investigated in the context of malaria -- in pathogens that rely on direct transmission. This work will demonstrate how new methods can provide unifying insight into patterns in critically important disease transmission systems and will enhance our ability to predict spillover of both filoviruses and many other zoonotic pathogens. Note that no human subjects, biohazards, or select agents will be involved in this project.",,2025,Oklahoma State University Stillwater,395614,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21732,5R01AI146172-03,Dissecting catalytic and regulatory functions of nonsegmented negative strand RNA viral polymerases,"Non-segmented negative strand (NNS) RNA viruses, such as rabies virus (RABV), human respiratory syncytial virus (HRSV), human parainfluenza virus type 3 (HPIV3), and Ebola virus (EBOV), pose continuing threats to human health, but there are currently no established prophylactic and/or therapeutic countermeasures against most NNS RNA viral diseases. NNS RNA viruses possess a multifunctional RNA-dependent RNA polymerase (RdRp) large (L) protein, which catalyzes all enzymatic reactions required for viral RNA biogenesis (e.g., RNA synthesis, 5′-capping, cap methylation at the guanine-N7- and ribose-2′-O-positions, 3′-polyadenylation). All these enzymatic activities of the L proteins are unique and potentially druggable. Our goals are to elucidate the molecular mechanisms of RNA synthesis and processing with the L proteins and to develop anti-viral agents against them. To dissect the roles of the L proteins in RNA biosynthesis, we have developed a number of in vitro rhabdoviral RNA synthesis and processing systems for prototypic vesicular stomatitis virus (VSV) and RABV. Using these systems, we discovered that rhabdoviral L proteins catalyze unconventional mRNA capping with a novel GDP polyribonucleotidyltransferase (PRNTase, EC 2.7.7.88) domain. However, the mechanisms of pre- mRNA capping and methylation coupled to mRNA chain elongation remain largely unknown. Furthermore, virus- specific functions of L proteins have not been studied. We hypothesize that L proteins catalyze common enzymatic reactions via evolutionary conserved elements, but manifest virus-specific functions via diversified elements. This hypothesis will be rigorously tested by the following specific aims: to elucidate the mechanisms of (1) co-transcriptional mRNA maturation by rhabdoviral L proteins, (2) cap formation by pneumoviral and paramyxoviral L proteins, and (3) transcription and replication by filoviral L proteins. In Aim 1, we will determine the timing and order of pre-mRNA processing by the VSV L protein during mRNA chain elongation, leading to a new model of co-transcriptional mRNA maturation by L proteins of rhabdoviruses and, by extension, other NNS RNA viruses. In Aim 2, we will reveal common and diversified functions of putative PRNTase and methyltransferase domains of the HRSV and HPIV3 L proteins in mRNA cap formation. In Aim 3, we will provide a novel model for genome replication by the EBOV L protein that is significantly different from that by other NNS RNA viral L proteins. Collectively, the proposed studies will open up a new frontier in understanding how diversified NNS L proteins carry out each step of RNA synthesis and processing together with their cognate co- factor proteins. Our studies will provide foundations for the future development of antiviral agents targeting unique L domains of these significant NNS RNA viruses.",,2024,University Of Toledo Health Sci Campus,347625,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Filoviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21733,5U01AI151814-02,EpiCenter for Emerging Infectious Disease Intelligence,"Project Summary/Abstract: The Epicenter for Emerging Infectious Disease Intelligence brings together a consortium of leading research institutions to advance an understanding of viral emergence from wildlife into humans living in forest and rapidly urbanizing ecosystems. Our work will enhance preparedness for disease emergence events in the Congo Basin and Amazon Basin forest regions and facilitate response efforts at the source of emergence. Our multidisciplinary team has internationally recognized expertise in infectious disease epidemiology, virology, human health, animal health, medical entomology, microbiology, and disease modeling. Our proposed activities integrate human, animal, and vector surveillance to enable insight into cross-species disease transmission and facilitate responsiveness to evolving needs that impact country, regional, and global emerging infectious disease risk. In our initial work, we propose to investigate the epidemiology of arboviruses and filoviruses, which include emerging viruses currently threatening global health security. We will evaluate disease transmission dynamics at the primary stage of emergence in humans, in forest communities where people are highly susceptible to virus spillover from wildlife and mosquitos. We will also investigate these viruses in the second stage of emergence, in urban centers peripherally connected to forests, where viruses have adapted to human-to-human transmission (by direct or vector-borne transmission). Targeted filoviruses and arboviruses at proposed sites in Uganda and Peru represent a range of emergence histories, from recent emergence events, to seasonal and annual re- emergence events, to introduction events where viruses have adapted to entirely new ecosystems, vectors, and vertebrate hosts. Research at these sites will advance our understanding of cross-species transmission for viruses across this spectrum of emergence. Our work will optimize best practices in acute febrile illness surveillance in high-risk communities coupled with wildlife and entomologic risk characterization studies to facilitate deployment of next generation techniques in early detection of virus emergence and monitoring of sustained transmission in at-risk communities. Our consortium has a demonstrated commitment to strengthening international capabilities for emerging infectious disease research in resource-limited countries. We are well- poised to contribute to important advances in capacity in the Amazon and Congo Basin forest region with partners in Uganda and Peru for completion of our proposed project and long-term sustainability for the greater region and across the Emerging Infectious Disease Research Center network.",,2025,University Of California At Davis,1613124,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Disease transmission dynamics",2020 +P21734,1R21AI154336-01A1,Tunneling nanotubes as an alternate route of Ebola virus dissemination,"Ebola virus (EBOV) is an emerging, dangerous virus that causes increasingly more frequent outbreaks of a systemic, hemorrhagic disease in human populations. Approved countermeasures to prevent or treat EBOV disease are currently limited. Macrophages are the initial cells targeted by EBOV, and due to their migratory properties are believed to rapidly disseminate the virus to distant tissues and organs despite the lack of experimental evidence. In current models, EBOV propagates infection through the cell-free form, where virus particles enter the cell, replicate the genome, and then assemble/egress to challenge neighboring cells. We have preliminary data suggesting that EBOV may exploit an alternative mode to spread infection (in parallel with the established model): viral nucleocapsids via tunneling nanotubes (TNTs), an actin-based intercellular communication system that allows direct exchange of cytoplasmic material between connecting cells. EBOV infection induces formation of intercellular connections containing virus nucleocapsid protein in primary human endothelial cell and macrophage populations. These connections support cell-to-cell transfer of the nucleocapsid protein in the absence of the virus. The data also show that EBOV can efficiently replicate in endothelial cells devoid of factors critical for virus entry, after initial retardation, and that the replication is compromised in cells depleted of host M-Sec, a central factor for TNT formation. This proposal aims to interrogate the interactions between EBOV and TNTs through two Specific Aims. In Aim 1, we will determine if TNTs are the intercellular connections induced by EBOV to spread infection in human endothelial cells and macrophages. In Aim 2, we will determine if EBOV spreads infection through intercellular transfer of nucleocapsids. Our discoveries will establish an alternate model of EBOV dissemination within the host, laying the groundwork for further investigations into pathogenesis of filoviruses. Importantly, these findings may lead to development of novel strategies to target EBOV and related viruses.",,2023,TEXAS BIOMEDICAL RESEARCH INSTITUTE,297000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21736,1R01AI151144-01A1,Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.,"ABSTRACT This project focuses on understanding the role that the unique physiology of bats plays in their ability to act as host reservoirs for diseases that can spill over to humans. The project will be carried out under field conditions in Uganda on three species of bats that have varying links to the spread of Ebola virus (EBOV) to humans. By comparing the ability of these three species of bats to respond to Ebola-like immune challenges, this work will help identify the characteristics that contribute to spillover risk. In the long term, this work will help identify host species for EBOV and other related viruses that present risk to humans. It will also help explain how different species of bats respond to different types of viral infections. The main focus of this project will be to identify behaviors and molecular pathways that enable reservoir hosts to tolerate infections, providing critical insight into one of the mechanisms that leads to spillover. This work is driven by the hypothesis that some bat species have coevolved with particular types of viral infections and, therefore, have adapted mechanisms to minimize pathology during infection. Bats are globally biodiverse and have many unique ecological and physiological adaptations, including flight and the ability to employ both hypo- and hyperthermic body temperature regulation. This project focuses on three bat species chosen because they are in close contact with humans, their habitats cover the range of EBOV exposure risk, and they have divergent coevolutionary histories with viral pathogens; two of the three species have significant ties to EBOV epidemiology. This project addresses these questions under natural conditions in the field by taking the innovative approach of using EBOV virus-like particles as a proxy for experimental infection with biohazardous pathogens. This project has three specific aims that will allow the achievement of its goals. First, the project tests the hypothesis that specific African bat species will display signatures of EBOV disease tolerance in response to challenge with EBOV virus-like particles, and thus are likely to be natural reservoir hosts. These experiments will provide significant insight into disease tolerance in bats and the potential identity of EBOV reservoir(s). Second, this project tests the hypothesis that bats display variable levels of disease tolerance that depend upon innate immune pathways that have undergone unique evolutionary selection in bats. Third, this project explores whether tolerance of and resistance to viral infection are facilitated by the unique metabolic behaviors of bats, namely that they can depress metabolism and enter torpor to conserve energy and can elevate metabolism and thus temperature during flight. The role of changes in body temperature is poorly understood and these experiments will identify whether these physiological responses contribute to immunological tolerance and resistance in important disease reservoirs. Together, the successful completion of these goals will help determine whether infection tolerance confers on African bat species the ability to serve as reservoir hosts for virulent zoonotic viruses and will identify molecular, physiological, and behavioral mechanisms that contribute to tolerance phenotypes.",,2026,Bucknell University,611428,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +P21737,1R21AI164268-01,Intelligently predicting viral spillover risks from bats and other wild mammals,"PROJECT SUMMARY The transmission or ‘spillover’ of wildlife viruses to humans is a critical threat to global health, with outbreaks of viral pathogens like filoviruses, paramyxoviruses, and coronaviruses all originating in wild mammals. A key outstanding question is whether specific taxonomic groups, such as bats, warrant extra surveillance as ‘special reservoirs’ of viruses that are potentially pathogenic to humans. However, existing host-virus datasets are not sufficiently resolved to predict fine-grain risk for species or genera. An effective response must therefore address two core aims: (i) synthesizing knowledge regarding virus-to-mammal interactions; and (ii) using that knowledgebase to robustly predict future spillover events (i.e., zoonotic risk). To enable robust analysis and reusability of public datasets of NIAID’s Bioinformatics Resource Center (BRC; especially NCBI Virus and Virus Pathogen Resources, ViPR), the project will develop Host-Virus Data Intelligence to address three main problems for data reuse: confidence of the taxonomic assignments of mammals and viruses in observations; confidence in the evidence for proposed mammal-virus interactions; and connecting all the relevant data in published texts that are hidden from existing databases. The project team will construct a novel bioinformatic pipeline that will digitally connect taxonomic knowledge, use it to search dark data to find evidence of potential host-virus interactions, and then link it together using metadata layers (‘data about the data’) to form a more expansive host-virus knowledge graph than previously feasible. The project’s computational approach leverages information extraction methods in natural language processing as well as novel applications of artificial intelligence methods such as probabilistic inductive logic programming. A key anticipated outcome is to expand the dataset of host-virus interactions by 3-fold compared to comprehensive existing datasets. The proposed project will lay the foundation for a new generation of work reusing host-virus interaction data to test previously inaccessible hypotheses about how species’ traits impact viral spillover to humans. Shifting the paradigm to graph-based analyses, compared to purely taxonomic representations of host-virus interactions, will allow researchers to directly investigate the impact of ecosystem structure and human encroachment upon viral loads. Determining whether all mammals have equal risk of viral spillover, or whether some groups have higher taxon-specific zoonotic risk (e.g., horseshoe bats, murid rodents), is critical information for public health workers and epidemiologists. More definitive risk quantification will also help researchers identify which ecophysiological adaptations predispose certain groups to tolerating more viruses, which may in turn lead to clinical treatments by modeling the immune responses of wild mammals. Filling the identified gaps in host-virus knowledge is therefore essential to aid the progress of zoonotic disease research in the wake of COVID-19.",,2023,Arizona State University-Tempe Campus,244519,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing | Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Health Systems Research","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Health information systems",2021 +P21738,1R43AI157684-01A1,Stimulating innate immunity to protect against Ebola virus infection,"Abstract. Filoviruses such as Ebola and Marburg viruses are Category A pathogens (pathogens that provide the highest risk to national security and public health) on NIAID's list of emerging infectious diseases due to their ease of dissemination, high mortality rates, and potential use as bioterrorism weapons. There is a need for fast acting, easy to use, and more effective medicines to protect against and improve survival from Ebola virus infection. Vaccines in development require at least 10 days for subjects to develop immunity and thus are not useful for treating newly infected patients or protecting non-vaccinated healthcare providers and first responders in an emergency outbreak situation. Antibiotics and antibody cocktails under study require intravenous infusion and resistance may develop through random or directed virus mutation. An alternative and potentially synergistic approach for protecting against Ebola virus infection is to stimulate the innate arm of the host immune system to resist viral infection. Macrophages and dendritic cells typically are the first cells infected by Ebola virus. Upon entry, the virus replicates and expresses proteins that interfere with the host cell's ability to block viral infection. The virus also causes host cells to secrete proinflammatory cytokines and chemokines that attract other myeloid cells to propagate the infection and results in a dysfunctional immune response unable to control the virus. Interferon gamma (IFNG) quickly (within hours) activates macrophages and dendritic cells so that they resist infection by Ebola and other viruses, as well as infection by several Category A facultative intracellular bacterial pathogens such as Tularemia and Burkholderia. Thus, IFNG has the potential to be an effective therapy against several deadly bioterrorism threats. However, IFNG has a very short in vivo half-life, poor bioavailability, required intraperitoneal injection for efficacy in preclinical studies, and has a narrow efficacy window, all of which limit the protein's utility as an Ebola therapy. We created a long- acting human IFNG analog (PEG IFNG) that has superior bioavailability and a longer half-life following subcutaneous injection and significantly greater efficacy than IFNG in animals. We hypothesize PEG-IFNG will be significantly more effective than IFNG at preventing morbidity and mortality from Ebola virus infection both as a protectant for pre-exposure prophylaxis and as a mitigator for post-exposure prophylaxis. We will test this hypothesis by comparing efficacy of a murine PEG IFNG homolog and murine IFNG administered pre and post infection for reducing morbidity and mortality from lethal Ebola virus infection in mice, as measured by survival, weight gain and clinical sickness scores. These studies will lead to an effective treatment that confers protection within hours and which can be administered easily (subcutaneous injection) to patients who recently contracted Ebola virus, as well as to first responders and healthcare providers in an emergency outbreak situation. Stimulating innate immunity using PEG IFNG will protect against Ebola virus and multiple other intracellular Category A pathogens such as Tularemia and Burkholderia that replicate within macrophages.",,2022,"BOLDER BIOTECHNOLOGY, INC.",300000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +P21739,5R01AI152246-02,Structure-based Vaccine Design for CCHFV,"Project Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) causes a life-threatening tick-borne disease in humans. The disease presents as a severe form of hemorrhagic fever with a case fatality rate of 10â€Â""40%. CCHFV outbreaks have spanned a wide geographic area ranging from Western and Central Asia, the Middle East, Africa and Southern Europe. Increasing global temperatures, migratory birds, and the international livestock trade have all potentially contributed toward the spread of Hyalomma ticksâ€Â""the primary vector for CCHFV. Expanding endemic zones, widespread morbidity and significant mortality make CCHFV an acute threat to public health and thus is listed as a NIAID Category A priority pathogen. The viral genome encodes a glycoprotein precursor that is processed into two structural glycoproteinsâ€Â""Gn and Gcâ€Â""and two secreted glycoproteinsâ€Â""a mucin-like domain and GP38. Protective antibodies have been isolated that target Gc or GP38, suggesting that these two proteins should be given priority for vaccine development. Here we propose to engineer Gc- and GP38-based immunogens that focus the immune response onto broadly conserved epitopes that are capable of eliciting protective antibody responses. To accomplish our goal, we will structurally characterize CCHFV glycoproteins and their interactions with human-derived antibodies, rationally engineer vaccine antigens based in part on the structural information, and characterize the immune responses elicited by these antigens in animal models. These results will be used to guide further improvements of the immunogens, including display on self-assembling multi-valent nanoparticles, and the most promising candidates will be evaluated in a lethal murine model of CCHFV challenge. Given our expertise, unique reagents, and preliminary data, we are confident that we can deliver a state-of-the-art subunit vaccine candidate with the potential to induce cross-reactive protective antibodies, thereby satisfying an unmet need against this NIAID Category A tick-borne pathogen.",,2025,University Of Texas At Austin,428507,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +P21741,1R41AI152745-01A1,Whispering Gallery Mode Devices for the Rapid Detection of Pan-Filoviruses,"Project Summary Filoviruses, including the Ebola viruses, Marburg viruses, and Cueva virus, are a class of pathogens with enormous health implications. Filoviruses have been implicated in numerous outbreaks in Africa, including the ongoing outbreak in the Democratic Republic of Congo (DRC), potential risk as an agent of bioterrorism, and the potential risk of transmission to non-endemic countries such as the United States. Critical in both the management of outbreaks as well as the treatment of infected patients are specific and rapid diagnostic tests. Despite the critical health risk posed by these pathogens, current diagnostic techniques utilizing PCR and ELISAs have significant limitations, including the need for centralized laboratories, cold-chain custody, and limited diagnostic ability in the early stages of infection. This proposal seeks to fill this gap and leverage a highly sensitive class of optical sensors, whispering gallery mode (WGM) devices, for the rapid detection of filovirus glycoproteins (GP) and the ebolavirus soluble glycoprotein (sGP), two highly sensitive biomarkers for filoviruses. WGM sensors are a unique class of optical devices in which light is confined to a small volume, therefore leading to an enormous enhancement in signal response. In addition to their sensitivity, these devices also offer the advantages of inexpensive and scalable fabrication costs, the ability to be integrated with conventional electronics, and the potential for multiplexed measurements. In combination with these devices will be antibodies against filovirus GP and sGP, the latter an enormously powerful sentinel biomarker that is positive hours to days before presentation of symptoms in infected individuals. This academic-industry partnership will develop a rapid and sensitive diagnostic test for filovirus GP and sGP, and subsequently lay the foundation for the developing this technology into a powerful, field-deployable device for filovirus detection.",,2022,"INTEGRATED BIOTHERAPEUTICS, INC.",299939,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21742,1R21EY031465-01,Predicted Role of Ebola VP40-Host Interactions in Ocular Pathology and Persistence,"Ebola virus (EBOV) can cross cellular barriers, establish persistence, and re-emerge in survivors months later in the eye, central nervous system, and semen, leading to long term pathology and sequelae. Indeed, a wide spectrum of ocular complications, including hemorrhages, blindness, and uveitis, have been reported following both acute EBOV infection and during long-term convalescent stages. The mechanisms by which filoviruses enter, persist, and re-emerge in the eye remain unknown. Retinal pigment epithelial (RPE) cells are permissive for EBOV infection and are thought to serve as the intraocular reservoir for persistence and spread of EBOV. Based on our preliminary data, we hypothesize that EBOV VP40 (eVP40) contributes to the spread of EBOV to the human eye by interacting with tight junctional (TJ) complex proteins in the RPE and/or corneal endothelium, thereby weakening these barriers to facilitate virus infection and spread during acute infection, as well as during re-emergence from a persistent state. Specifically, we have shown that the PPxY motif conserved in filovirus VP40 proteins can interact with select host WW-domain bearing proteins that are involved in maintaining and regulating the physical and functional integrity of cellular TJs. These VP40 interactors include MAGI3, a member of the MAGUK superfamily of proteins, that functions as an adaptor/scaffolding protein to maintain junction integrity and barrier function as well as YAP and TAZ; paralogues and downstream effectors of the Hippo signaling pathway that regulate genes involved in cell proliferation and migration and junctional integrity. The interaction of YAP/TAZ and MAGI3 with the PPxY motifs of filovirus VP40 is particularly intriguing, as these host proteins are also regulated by the binding of their WW-domains to the N-terminal PPxY motifs of the host protein AMOT (Angiomotin). Indeed, Amot negatively regulates YAP activity by binding and sequestering YAP at TJs, and promotes TJ assembly and integrity by interacting with the MAGI family of scaffolding proteins. Since Amot, via its PPxY motifs, appears to be a “master regulator” of TJ formation and function, we hypothesize that the PPxY motifs of filovirus VP40 may compete with those of Amot to disrupt TJ formation and function in virus infected cells, thereby enhancing cellular permeability and virus spread. In this high risk, high impact proposal, we will use a powerful and innovative eye-on-a-chip technology to provide a human cell-based model system with an unprecedented level of physiological realism to investigate: 1) the role of VP40 in altering the most essential barriers of the human eye, and 2) to determine whether our previously validated PPxY inhibitors not only can block VP40-mediated egress and spread, but also prevent VP40-mediated disruption of TJ barriers and disease progression in these eye models. This exploratory and innovative approach will provide new fundamental insights into the molecular mechanisms of filoviral-host interactions in the human eye that may contribute to transmission and pathogenesis of these deadly viruses, and may identify a new therapeutic strategy to treat filovirus infections in these ocular tissues.",,2022,University Of Pennsylvania,243000,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +P21743,1R44AI150263-01A1,A modular platform for infectious disease surveillance at point-of-need.,"ABSTRACT We propose to develop a point-of-need system for differential molecular identification of filoviruses from syndromically similar infections. Our goal is to enable rapid, sensitive, and specific identification of quarantinable infections to reduce nosocomial risk and improve outbreak response. The platform will simultaneously test 12 genomic markers at the genus and strain level using a modular microfluidic design that allows for rapid panel update and expansion. In Phase I we will develop an assay for pan-filovirus (pFi), followed by expansion of the panel and system integration in Phase II. The expanded panel will add pan-flavivirus (pFa) and pan-Plasmodium (pPa) detection as well as strain-specific targets for Ebola, Marburg, Dengue, Yellow Fever, and Malaria. Strain specific tests will enable better patient triage/treatment during an outbreak and improve disease surveillance in non-outbreak settings. The panel will require a 50 μL sample of whole blood and will achieve highly specific detection in < 30 minutes. To achieve this goal, we will combine Redbud Labs’ expertise in microfluidics and systems with the diagnostic development expertise of the Diagnostics Program at PATH (Seattle, WA), and the VHF testing/processing capabilities of the Connor Lab at Boston University (part of the BSL-4 facilities at NEIDL).",,2022,"REDBUD LABS, INC.",299268,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21746,1R21AI153475-01,A Transgenic Mouse Model to Study Ebolaviruses and other Filoviruses,"PROJECT SUMMARY Ebola viruses and other members of the filovirus family cause severe and often lethal infections. While some progress has been made in regards to the development of experimental countermeasures and insights into the highly pathogenic nature of these viruses, there are still many more unanswered questions, and further advancement is needed towards the development of pan-filovirus therapeutic agents and vaccines. A significant hurdle to research on filoviruses is the accessibility and cost associated with high-containment, biosafety level- 4 laboratories. To partially alleviate this issue, we previously established a replication-defective Ebola virus based on the Zaire ebolavirus (EBOV) genome. This virus, which lacks the essential viral gene VP30 (termed EBOVÃŽÂ""VP30), is biologically inert and safe to use outside of highly specialized BSL-4 containment. In engineered cell lines that stably express EBOV VP30, the virus becomes replication-competent; thus it is a perfect EBOV surrogate for in vitro research given that EBOVÃŽÂ""VP30 resembles authentic virus in its life cycle, morphology, protein composition, and growth kinetics. After extensive safety testing both in cell culture and in animal models, the CDC and the Office of Science Policy at the NIH classified EBOVÃŽÂ""VP30 as a BSL-2 agent and removed the virus from Select Agent regulations. Since then, this in vitro system to study EBOV has been requested by and distributed to several other research laboratories. The next step to advance the EBOVÃŽÂ""VP30 system is to develop an EBOV VP30 transgenic animal model to support virus replication. Previously, we generated a transgenic mouse line that expressed EBOV VP30 under the control of the chicken beta-actin promoter (CAG). Although we were able to detect VP30 mRNA in key organs, such as the liver, and functional VP30 protein in cells, such as fibroblasts, we were unable to detect VP30 mRNA and functional protein in monocyte-derived macrophages, the first target of EBOV infection and a cell type essential for virus dissemination throughout the body. Here, we propose to generate a new transgenic mouse line with EBOV VP30 expression under the control of the CD45 promoter, a promoter specific for expression in hematopoietic cells, including monocytes, macrophages, and dendritic cells. Once we confirm the expression and function of VP30 in these cell types, particularly macrophages, we will cross our two different VP30 transgenic lines (CAG and CD45) to generate a double knock-in transgenic mouse line. Once established, we will infect these transgenic mice with mouse-adapted EBOVÃŽÂ""VP30 and characterize the phenotype. We will also generate chimeric versions of EBOVÃŽÂ""VP30 with glycoproteins from other filoviruses and examine the phenotype of these chimeric viruses in the transgenic mice. After safety testing, this new small animal model will be an ideal in vivo surrogate for the authentic mouse model for EBOV infection. For the first time, a transgenic mouse model will be available that can be used efficiently and safely outside of BSL-4 containment to examine EBOV pathogenesis and accelerate the development and evaluation of countermeasures.",,2022,University Of Wisconsin-Madison,206568,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2020 +P21747,1R21AI152200-01,Engineering pathogen triggered biomineralization to enable a new generation of point-of-care tests,"ABSTRACT Biomineralization is a coalescence of organic (soft) and inorganic (hard) chemistries where proteins or peptides borne on a close-knit macromolecular scaffold serve as nucleation sites for salts to precipitate from solution and grow into crystals. When these proteins or peptide motifs are free in solution phase at low concentrations, biomineralization does not occur. We aim to harness this concentration dependent phenomenon to formulate a new generation of pathogen specific assays. Biomineralizing motifs will be fused to antibodies specific to macromolecular scaffolds of pathogens, so that the presence of pathogen will cluster the fusions, concentrating them to trigger crystal formation. The approach requires no washing steps and should give a visible readout in this feasibility study for an exploratory point-of-care assay. We will first isolate protein motifs capable of driving the formation of physiological buffer salt crystals from solutions. We will then employ Filovirus preparations and pre-existing antibodies against polyvalent viral cores to assess biomineralization potential of motif-antibody fusions and establish limits of detection (LOD) for Ebola and Marburg viruses to benchmark our system. Finally, we will engineer mutants of the motifs to understand drivers of biomineralization, accelerating the process, reducing assay times and lowering LOD. While initially meant as a point-of-care assay feasibility study, the process should also be addressable by conductivity measurements and imaging for biosensing applications. If successful, future developments could also include retuning the process to operate against adjacent nucleic acid sequence targets by fusing the biomineralizing motifs to oligonucleotide probes. Convenient and inexpensive diagnostics that don’t require vast infrastructure investment are desperately needed in the field, especially for emerging zoonoses in resource limited geographies. Our feasibility study will show whether biomineralization can contribute to solving this problem and offer a paradigm shifting parallel track for further development to help safeguard human health.",,2022,TEXAS BIOMEDICAL RESEARCH INSTITUTE,297000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21748,1R01AI156866-01,Spillover of Ebola and other filoviruses at ecological boundaries,"More than half of all infectious disease outbreaks across the globe are zoonotic, involving pathogen spillover from animal reservoirs to humans. Ebola and other filoviruses rank among the most deadly zoonoses. Recent large outbreaks with mortality in the thousands both in humans and wildlife underscore the pressing need to better understand the factors promoting filovirus spillover. Although spillover is commonly defined as a pathogen crossing species boundaries, there are relatively few empirical studies or modeling frameworks that explicitly consider ecological boundaries across which spillover occurs. Crossing ecological boundaries involves processes that occur at many levels of organization: physiological processes at the individual level, interspecies interactions between individuals at the population level, interactions between populations of different species at the community level, and interactions between ecological communities within landscapes. Processes accelerating spillover often involve human activities such as habitat encroachment and land conversion, which are themselves ultimately driven by socioeconomic factors. In the context of Ebola and other filoviruses in Africa, we will develop the data sets, theoretical models and statistical tools needed for a general descriptive and predictive framework for spillover at ecological boundaries. Our project will follow an iterative design where results from mechanistic models are used to refine patterns that we test for empirically, and statistical models of large-scale data allow us to more realistically parameterize mechanistic models. Our work will test the generality of specific theories that so far have been applied only to a limited number of study systems. For example, ours will be among the first attempts to test the influence of Schmalhausen’s law -- an evolutionary theory that may explain the tendency for large outbreaks to occur at the edges of species ranges or during unusual weather conditions and which to date has primarily been investigated in the context of malaria -- in pathogens that rely on direct transmission. This work will demonstrate how new methods can provide unifying insight into patterns in critically important disease transmission systems and will enhance our ability to predict spillover of both filoviruses and many other zoonotic pathogens. Note that no human subjects, biohazards, or select agents will be involved in this project.",,2025,University Of Georgia,472934,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P21749,1R21AI144215-01A1,CD40 regulation of acute virus infection,"CD40 signaling is well established to enhance development and maintenance of adaptive immunity. However, the role of CD40 signaling during innate immune responses is more poorly studied and an important role for CD40 signaling in rapid control of acute virus infections is not currently appreciated. Here, we provide strong preliminary findings that CD40 signaling is critical for early stimulation of innate immune pathways in peritoneal macrophages, resulting in control of acute viral infection. In these proposed studies, we will use both Ebola virus (EBOV) and a BSL2 model virus of EBOV to identify the CD40+ cellular compartment(s) required for protection and understand the breadth of cell populations that use CD40 signaling to control EBOV infection. Elucidation of these cell populations will elucidate targeted approaches that can lead to therapeutic interventions.",,2022,University Of Iowa,259730,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P21750,3R01AI150246-01S1,Small Molecule Screening to Identify Novel Sars-CoV-2 Therapeutics ,"Summary The current outbreak of the coronavirus in China (SARS-CoV-2) has spread rapidly. There are experimental drugs which will be tested; however, there are no approved therapeutics or vaccines. Indeed, there are tests underway to determine whether remdesivir, which was developed against filoviruses, can be repurposed against SARS-CoV-2 infection. It would be transformative if we could identify additional small molecules that could be repurposed to treat the outbreak of SARS-CoV-2 infection. Given that the goal of the parent grant (R01AI150246) is to discover antivirals active against bunyaviruses, based on findings from cell based screening, and that we have broad expertise in diverse viruses, we are applying for Supplemental funding (notice number NOT-AI-20-030, PA-18-035) to expand the scope of the existing grant to use the same methods (small molecule screening) to identify antiviral therapeutics active against SARS-CoV-2 infection. We will screen two libraries of known bioactives to potentially repurpose existing therapeutics. First, we will test a library of innate immune agonists (~100 PAMPs) for their ability to block SARS-CoV-2 infection in human cells including airway cells. Second, we will screen another ‘actionable’ library that I have created as the Director of the High-throughput Screening core at UPENN. We created a library of ~3000 drugs that includes ~1500 FDA approved compounds, ~1000 drugs in clinical trials and the remaining drugs have known targets. This library has been used for repurposing (as is being done with the Gilead drug remdesivir that was originally developed against filoviruses) to more rapidly identify active therapeutics for future testing in humans. We will also determine if any of our active antivirals act synergistically with remdesivir since this drug is currently under development for use against COVID-19. We expect to identify additional drugs with activity against SARS-CoV-2.",,2022,University Of Pennsylvania,111910,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P21751,3R01AI150246-02S1,Small Molecule Screening to Identify Novel Sars-CoV-2 Therapeutics ,"Summary The current outbreak of the coronavirus in China (SARS-CoV-2) has spread rapidly. There are experimental drugs which will be tested; however, there are no approved therapeutics or vaccines. Indeed, there are tests underway to determine whether remdesivir, which was developed against filoviruses, can be repurposed against SARS-CoV-2 infection. It would be transformative if we could identify additional small molecules that could be repurposed to treat the outbreak of SARS-CoV-2 infection. Given that the goal of the parent grant (R01AI150246) is to discover antivirals active against bunyaviruses, based on findings from cell based screening, and that we have broad expertise in diverse viruses, we are applying for Supplemental funding (notice number NOT-AI-20-030, PA-18-035) to expand the scope of the existing grant to use the same methods (small molecule screening) to identify antiviral therapeutics active against SARS-CoV-2 infection. We will screen two libraries of known bioactives to potentially repurpose existing therapeutics. First, we will test a library of innate immune agonists (~100 PAMPs) for their ability to block SARS-CoV-2 infection in human cells including airway cells. Second, we will screen another ‘actionable’ library that I have created as the Director of the High-throughput Screening core at UPENN. We created a library of ~3000 drugs that includes ~1500 FDA approved compounds, ~1000 drugs in clinical trials and the remaining drugs have known targets. This library has been used for repurposing (as is being done with the Gilead drug remdesivir that was originally developed against filoviruses) to more rapidly identify active therapeutics for future testing in humans. We will also determine if any of our active antivirals act synergistically with remdesivir since this drug is currently under development for use against COVID-19. We expect to identify additional drugs with activity against SARS-CoV-2.",,2022,University Of Pennsylvania,336020,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P21752,7R01AI146172-02,Dissecting catalytic and regulatory functions of nonsegmented negative strand RNA viral polymerases,"Non-segmented negative strand (NNS) RNA viruses, such as rabies virus (RABV), human respiratory syncytial virus (HRSV), human parainfluenza virus type 3 (HPIV3), and Ebola virus (EBOV), pose continuing threats to human health, but there are currently no established prophylactic and/or therapeutic countermeasures against most NNS RNA viral diseases. NNS RNA viruses possess a multifunctional RNA-dependent RNA polymerase (RdRp) large (L) protein, which catalyzes all enzymatic reactions required for viral RNA biogenesis (e.g., RNA synthesis, 5′-capping, cap methylation at the guanine-N7- and ribose-2′-O-positions, 3′-polyadenylation). All these enzymatic activities of the L proteins are unique and potentially druggable. Our goals are to elucidate the molecular mechanisms of RNA synthesis and processing with the L proteins and to develop anti-viral agents against them. To dissect the roles of the L proteins in RNA biosynthesis, we have developed a number of in vitro rhabdoviral RNA synthesis and processing systems for prototypic vesicular stomatitis virus (VSV) and RABV. Using these systems, we discovered that rhabdoviral L proteins catalyze unconventional mRNA capping with a novel GDP polyribonucleotidyltransferase (PRNTase, EC 2.7.7.88) domain. However, the mechanisms of pre- mRNA capping and methylation coupled to mRNA chain elongation remain largely unknown. Furthermore, virus- specific functions of L proteins have not been studied. We hypothesize that L proteins catalyze common enzymatic reactions via evolutionary conserved elements, but manifest virus-specific functions via diversified elements. This hypothesis will be rigorously tested by the following specific aims: to elucidate the mechanisms of (1) co-transcriptional mRNA maturation by rhabdoviral L proteins, (2) cap formation by pneumoviral and paramyxoviral L proteins, and (3) transcription and replication by filoviral L proteins. In Aim 1, we will determine the timing and order of pre-mRNA processing by the VSV L protein during mRNA chain elongation, leading to a new model of co-transcriptional mRNA maturation by L proteins of rhabdoviruses and, by extension, other NNS RNA viruses. In Aim 2, we will reveal common and diversified functions of putative PRNTase and methyltransferase domains of the HRSV and HPIV3 L proteins in mRNA cap formation. In Aim 3, we will provide a novel model for genome replication by the EBOV L protein that is significantly different from that by other NNS RNA viral L proteins. Collectively, the proposed studies will open up a new frontier in understanding how diversified NNS L proteins carry out each step of RNA synthesis and processing together with their cognate co- factor proteins. Our studies will provide foundations for the future development of antiviral agents targeting unique L domains of these significant NNS RNA viruses.",,2024,University Of Toledo Health Sci Campus,347437,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2020 +P21753,1U01AI151814-01,EpiCenter for Emerging Infectious Disease Intelligence,"Project Summary/Abstract: The Epicenter for Emerging Infectious Disease Intelligence brings together a consortium of leading research institutions to advance an understanding of viral emergence from wildlife into humans living in forest and rapidly urbanizing ecosystems. Our work will enhance preparedness for disease emergence events in the Congo Basin and Amazon Basin forest regions and facilitate response efforts at the source of emergence. Our multidisciplinary team has internationally recognized expertise in infectious disease epidemiology, virology, human health, animal health, medical entomology, microbiology, and disease modeling. Our proposed activities integrate human, animal, and vector surveillance to enable insight into cross-species disease transmission and facilitate responsiveness to evolving needs that impact country, regional, and global emerging infectious disease risk. In our initial work, we propose to investigate the epidemiology of arboviruses and filoviruses, which include emerging viruses currently threatening global health security. We will evaluate disease transmission dynamics at the primary stage of emergence in humans, in forest communities where people are highly susceptible to virus spillover from wildlife and mosquitos. We will also investigate these viruses in the second stage of emergence, in urban centers peripherally connected to forests, where viruses have adapted to human-to-human transmission (by direct or vector-borne transmission). Targeted filoviruses and arboviruses at proposed sites in Uganda and Peru represent a range of emergence histories, from recent emergence events, to seasonal and annual re- emergence events, to introduction events where viruses have adapted to entirely new ecosystems, vectors, and vertebrate hosts. Research at these sites will advance our understanding of cross-species transmission for viruses across this spectrum of emergence. Our work will optimize best practices in acute febrile illness surveillance in high-risk communities coupled with wildlife and entomologic risk characterization studies to facilitate deployment of next generation techniques in early detection of virus emergence and monitoring of sustained transmission in at-risk communities. Our consortium has a demonstrated commitment to strengthening international capabilities for emerging infectious disease research in resource-limited countries. We are well- poised to contribute to important advances in capacity in the Amazon and Congo Basin forest region with partners in Uganda and Peru for completion of our proposed project and long-term sustainability for the greater region and across the Emerging Infectious Disease Research Center network.",,2025,University Of California At Davis,1677787,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | Disease transmission dynamics",2020 +P21754,1R01AI152246-01,Structure-based Vaccine Design for CCHFV,"Project Summary/Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) causes a life-threatening tick-borne disease in humans. The disease presents as a severe form of hemorrhagic fever with a case fatality rate of 10â€Â""40%. CCHFV outbreaks have spanned a wide geographic area ranging from Western and Central Asia, the Middle East, Africa and Southern Europe. Increasing global temperatures, migratory birds, and the international livestock trade have all potentially contributed toward the spread of Hyalomma ticksâ€Â""the primary vector for CCHFV. Expanding endemic zones, widespread morbidity and significant mortality make CCHFV an acute threat to public health and thus is listed as a NIAID Category A priority pathogen. The viral genome encodes a glycoprotein precursor that is processed into two structural glycoproteinsâ€Â""Gn and Gcâ€Â""and two secreted glycoproteinsâ€Â""a mucin-like domain and GP38. Protective antibodies have been isolated that target Gc or GP38, suggesting that these two proteins should be given priority for vaccine development. Here we propose to engineer Gc- and GP38-based immunogens that focus the immune response onto broadly conserved epitopes that are capable of eliciting protective antibody responses. To accomplish our goal, we will structurally characterize CCHFV glycoproteins and their interactions with human-derived antibodies, rationally engineer vaccine antigens based in part on the structural information, and characterize the immune responses elicited by these antigens in animal models. These results will be used to guide further improvements of the immunogens, including display on self-assembling multi-valent nanoparticles, and the most promising candidates will be evaluated in a lethal murine model of CCHFV challenge. Given our expertise, unique reagents, and preliminary data, we are confident that we can deliver a state-of-the-art subunit vaccine candidate with the potential to induce cross-reactive protective antibodies, thereby satisfying an unmet need against this NIAID Category A tick-borne pathogen.",,2025,University Of Texas At Austin,441966,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +P21755,1FI2GM137804-01,Elucidating the Mechanism of Ebola Virus Enterotoxigenicity,"PROJECT SUMMARY Ebola Virus Disease (EVD) is highly lethal with >20,000 cases reported during the 2014-16 West Africa epidemic and >2,800 cases reported during the ongoing epidemic in the Democratic Republic of the Congo. Ebola virus (EBOV) belongs to the Filoviridae family and encodes for 7 proteins including a single glycoprotein (EBOV-GP) that has been shown to play a crucial role in EVD pathogenesis. During EVD, gastrointestinal fluid loss via large volume watery diarrhea leads to hypovolemic shock, electrolyte imbalances, and increased mortality. Furthermore, feces are categorized as highly infectious, thus excessive fluid loss incites environmental contamination increasing the risk of nosocomial viral transmission. The physiological mechanisms of viral glycoproteins acting as enterotoxins and prompting high volume diarrhea have been well described. However, the molecular trigger and mechanisms describing how EBOV stimulates high volume watery diarrhea during EVD have never been studied. Our preliminary data in human intestinal cells suggests an enterotoxin- like behavior for EBOV-GP as it induces a rapid and dose-dependent increase in intracellular Ca2+ concentration that is mitigated by inhibition of Phospholipase C (PLC). Moreover, EBOV-GP stimulation induces activation of chloride channels. The working hypothesis is that EBOV-GP induces intracellular Ca2+ increase in the gastroinstestinal epithelia, triggering an apical surface ion transport dysregulation resulting in increased permeability and water secretion. The project goals are to determine if EBOV-GP acts as an enterotoxin, study if it triggers a malabsorptive or secretory process and fully elucidate the mechanisms leading to high-volume watery diarrhea during EVD. For this, the project has three specific aims conceptualized for using of small intestine and colon cells since they diverge in absorption and secretion processes. Aim 1 will study the contributions of Ca2+ sources in the increased levels of intracellular Ca2+ triggered by EBOV-GP and elucidate its upstream signaling pathway. Aim 2 will assess the dynamics of Na+ and Cl- across the cell membrane, cell permeability and fluid transport after EBOV-GP stimulation. Polarized cell cultures will be used to mimic the ions/fluid movement and directionality. Aim 3 will feature whole-cell patch clamp to identify the ion channels being altered by EBOV-GP. This project will be achieved using contemporary in-vitro assays and combine microscopy, molecular biology, electrophysiology and biophysics. The completion of this project will provide the awardee training in electrophysiology techniques advancing his career and complementing his immunology and cell biology background. The proposed project will provide the awardee the skill set to study host-pathogen interactions in the context of the interplay between electrophysiology, immunology and cell biology. This project has translational impact as it could lead to novel therapeutic targets and strategies for EVD high volume diarrhea, directly improving the patients prognosis and reducing viral transmission in healthcare settings in the field.",,2023,U.S. NATIONAL INST ALLERGY & INFECT DIS,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21756,3R01AI132178-04S1,Broad-spectrum antiviral GS-5734 to treat MERS-CoV and related emerging CoV,"Project Summary Zoonotic viruses, like filoviruses and coronaviruses (CoV), represent a continuous and growing threat to global public health because they unpredictably emerge causing devastating outbreaks of pandemic disease. In the 21st century, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged from zoonotic pools of viruses, causing severe disease in humans. MERS-CoV is endemic in camels in the Middle East with continuous new infections in humans. Although SARS-CoV is not currently a threat, several “prepandemic” SARS-like CoVs have been isolated from bats that replicate efficiently in human cells and are resistant to existing therapies. With the unpredictable overlap of human and wild animal ecologies, the potential for novel CoV emergence into humans is highly probable. Currently, there are no approved antiviral therapies for any human CoV infection. Broad-spectrum CoV therapies that control known human and zoonotic CoV infections would address an immediate unmet medical need and could counter future pandemic episodes. In partnership with Gilead Sciences, we have demonstrated that the nucleoside prodrug, GS-5734, is highly efficacious in inhibiting multiple human and zoonotic CoV in vitro and SARS-CoV in vivo. The primary goal of our program is to accelerate the preclinical development of GS-5734 and promote IND licensure for the MERS-CoV indication. To thoroughly evaluate the breadth of antiviral activity and predict efficacy against future emerging CoV, we will also assess efficacy against a panel of CoV representative of family-wide genetic diversity, including prepandemic zoonotic strains poised for emergence. Focusing on the highly pathogenic MERS-CoV, our unique partnership integrates: i) metagenomics and recombinant virus synthetic genome recovery, ii) primary human lung cell models, iii) cutting edge virology and biochemistry, iv) robust murine and primate models of human disease and v) state of the art metabolic and pharmacokinetic analysis. In Aim 1, we refine the pharmacokinetics, pharmacodynamics and breadth of GS-5734 through efficacy and metabolism studies in various primary human cells with a diverse array of human and zoonotic CoV and through the evaluation of in vivo efficacy in murine and non-human primate models of MERS- and SARS-CoV. In Aim 2, we select for resistance against SARS-CoV and MERS- CoV, and determine the effect of resistance on virus replication, fitness and susceptibility to treatment. In Aim 3, we determine if the mechanism of action of GS-5734 is a result of direct effects on viral RNA replication and/or alteration of antiviral immunity via deep sequencing and single molecule RNA fluorescence in situ hybridization of vehicle or drug treated infected cells and mice. We articulate a development strategy for broad- spectrum therapeutics that could be extended to a multitude of emerging viral pathogens threatening global public health.",,2022,UNIV OF NORTH CAROLINA CHAPEL HILL,458053,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21757,3R01AI132178-03S1,Broad-spectrum antiviral GS-5734 to treat MERS-CoV and related emerging CoV,"Project Summary Zoonotic viruses, like filoviruses and coronaviruses (CoV), represent a continuous and growing threat to global public health because they unpredictably emerge causing devastating outbreaks of pandemic disease. In the 21st century, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged from zoonotic pools of viruses, causing severe disease in humans. MERS-CoV is endemic in camels in the Middle East with continuous new infections in humans. Although SARS-CoV is not currently a threat, several “prepandemic” SARS-like CoVs have been isolated from bats that replicate efficiently in human cells and are resistant to existing therapies. With the unpredictable overlap of human and wild animal ecologies, the potential for novel CoV emergence into humans is highly probable. Currently, there are no approved antiviral therapies for any human CoV infection. Broad-spectrum CoV therapies that control known human and zoonotic CoV infections would address an immediate unmet medical need and could counter future pandemic episodes. In partnership with Gilead Sciences, we have demonstrated that the nucleoside prodrug, GS-5734, is highly efficacious in inhibiting multiple human and zoonotic CoV in vitro and SARS-CoV in vivo. The primary goal of our program is to accelerate the preclinical development of GS-5734 and promote IND licensure for the MERS-CoV indication. To thoroughly evaluate the breadth of antiviral activity and predict efficacy against future emerging CoV, we will also assess efficacy against a panel of CoV representative of family-wide genetic diversity, including prepandemic zoonotic strains poised for emergence. Focusing on the highly pathogenic MERS-CoV, our unique partnership integrates: i) metagenomics and recombinant virus synthetic genome recovery, ii) primary human lung cell models, iii) cutting edge virology and biochemistry, iv) robust murine and primate models of human disease and v) state of the art metabolic and pharmacokinetic analysis. In Aim 1, we refine the pharmacokinetics, pharmacodynamics and breadth of GS-5734 through efficacy and metabolism studies in various primary human cells with a diverse array of human and zoonotic CoV and through the evaluation of in vivo efficacy in murine and non-human primate models of MERS- and SARS-CoV. In Aim 2, we select for resistance against SARS-CoV and MERS- CoV, and determine the effect of resistance on virus replication, fitness and susceptibility to treatment. In Aim 3, we determine if the mechanism of action of GS-5734 is a result of direct effects on viral RNA replication and/or alteration of antiviral immunity via deep sequencing and single molecule RNA fluorescence in situ hybridization of vehicle or drug treated infected cells and mice. We articulate a development strategy for broad- spectrum therapeutics that could be extended to a multitude of emerging viral pathogens threatening global public health.",,2021,UNIV OF NORTH CAROLINA CHAPEL HILL,450462,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21758,5R01AI171200-02,Innate immune recognition and response to Rift Valley fever virus,"Rift Valley fever virus (RVFV) is widespread throughout the entire African continent and in some endemic areas over 50% of the population is exposed by adulthood. Antiviral responses induced by interferon (IFN) signaling can limit RVFV replication and inhibit RVFV pathogenesis in vivo. RVFV is known to infect mononuclear phagocytic cells (MPCs), hepatocytes, and neurons, consistent with its main clinical manifestations of acute febrile illness, hepatitis, or encephalitis. However, it is largely unknown how each of these cell types recognizes and responds to RVFV infection or how cell type specific innate immune responses modulate viral pathogenesis. The overall objective for this proposal is to determine how the mammalian host innate immune system recognizes and responds to RVFV infection and how this modulates viral pathogenesis. Our central hypothesis is that differential innate immune recognition and response by infected cells modulates viral pathogenesis. To test this hypothesis, we will 1) identify the innate immune sensors and effectors active in biologically relevant human primary cells, 2) define the contribution of key innate immune sensors and effectors in recognition and response to RVFV infection in vivo and 3) define the role of hematopoietic cell infection in RVFV pathogenesis in vivo. The results of this research will define the mechanisms of innate immune recognition and response following RVFV infection. Moreover, it will inform on cell type-specific responses to infection and how virally mediated antagonism of those responses contributes to viral pathogenesis.",,2027,University Of Pittsburgh At Pittsburgh,464676,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +P21759,5R01AI161765-03,Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis,"Project Summary/Abstract Rift Valley fever virus (RVFV) is a phlebovirus that belongs to the Phenuiviridae (formerly Bunyaviridae) family of negative-sense RNA viruses. As an emerging mosquito-borne virus, the significance of RVFV is highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of Priority Diseases. Recently, the Coalition for Epidemic Preparedness Innovations (CEPI) has also included RVFV as a part of their emerging infectious diseases vaccine program, further emphasizing the potential impact of RVFV on the global health and economy. While RVFV is endemic throughout sub-Saharan Africa, competent mosquito vector species are found in North America, highlighting the potential for emergence of RVFV in non-endemic countries, including the United States. During outbreaks, RVFV causes severe disease in livestock, including sheep and cattle, which dramatically impact the socioeconomic framework in resource limited settings. Humans are spill- over hosts, where infections can result in severe consequences, including hepatic necrosis, hemorrhagic fever, encephalitis, and retinal vasculitis. Despite its significance to human health and the potential to negatively impact the socioeconomic fabric of resource-limited countries where the virus is endemic, there is a lack of safe and efficacious prophylactic and therapeutic treatment options. This gap is in part due to our lack of knowledge on host factors that contribute to RVFV infection. To address this need, we conducted a genomic screen that defined several critical factors, including a potential entry factor, which we will characterize by a multidisciplinary approach. In support, we provide compelling preliminary data, including in vitro validation in host factor sufficient and deficient cells, transcomplementation studies, direct interaction between RVFV glycoprotein Gn and the host proteins in vitro, inhibition of the entry factor by endogenous ligands in vitro in multiple cell lines from evolutionarily distinct hosts, and preliminary results of protection from RVFV infection in two conditional knock out mouse models. Importantly, we have generated many key reagents, including most cell lines and proteins, and knock-out mice supporting the feasibility. Importantly, this work will be performed by highly productive and collaborative investigators with expertise in every aspect of the proposed studies, including biochemistry, RVFV pathogenesis, immunology, proteomics, structural biology, and virology. Completion of the proposed studies will define novel host or entry factors for RVFV in target cells with tissue-specific relevance. As a specific receptor for RVFV has not previously been identified, these studies will provide important information for design of therapeutic interventions to prevent RVFV infection and disease. At the completion, we expect to fill a key gap in the field and to provide novel targets for therapeutic development.",,2026,Washington University,739505,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2021 +P21760,5R41AI165102-02,Discovery of Bunyaviral Endonuclease Inhibitors for Antiviral Therapy,"Abstract Segmented negative-sense, single-stranded RNA viruses (sNSVs), which include bunyaviruses, are causative agents of human diseases. Rift Valley Fever Virus (RVFV), a bunyavirus, causes hemorrhagic fever in humans with a case fatality rate of patients developing hemorrhagic fever reaching approximately 50% and has been classified by the NIAID as a Category A Priority Pathogen. RVFV is mosquito-borne, but is also capable of using a wide range of insect vectors with potential to spread to Europe and the Americas. RVFV has the potential to cause significant global health and economic impact. Unfortunately, there are no FDA-approved drugs or vaccines for the treatment of the RVFV infection. Therefore, there is an urgent medical need for more potent therapeutics tailored for RVFV. The overall goal of this project is to identify and develop small molecule prophylactics and/or therapeutics for RVFV infections and preferably also for infections of other highly related bunyaviruses. The strategy is to address the unmet medical need by identifying small molecule inhibitors targeting the enzymatic activity of the essential RVFV endonuclease, which exhibits significant structural similarity to other sNSV endonucleases. The approach is to leverage the team’s experience with bunyaviral endonucleases and a homogeneous FRET-based biochemical assay to identify small molecules that inhibit the enzymatic activity of bunyaviral endonucleases. In Preliminary Studies, we developed a FRET-endonuclease activity (FRET-EA) assay for RVFV endonuclease and applied the assay in a low/medium-throughput format with Z’-factors ≥0.9. The FRET assay confirmed the inhibition of an FDA approved antiviral to treat Influenza virus (IAV), Baloxavir acid (BXA), against IAV endonuclease. In Phase I, for Aim 1, the FRET-EA assay will be optimized for high-throughput screening. Biochemical and cellular secondary assays, including FRET, thermal shift, and cell-based infectious assays, will be optimized to further evaluate confirmed hits. In Aim 2, the FRET- EA HTS will be applied to diverse chemical libraries of ≥250,000 small molecules for the identification and confirmation of small molecules that inhibit the enzymatic activity of RVFV endonuclease. In Aim 3, hits identified in Aim 2 will be validated in secondary assays for binding to endonuclease, anti-sNSV spectrum, and potency against infectious RVFV. They will also be prioritized based on their drug-likeness and their ADME properties. In Phase II, we will perform structural based mechanism studies and further chemically optimize priority inhibitors for potency, selectivity, in vitro and in vivo pharmacokinetics properties and evaluate them in animal infection models.",,2024,"MICROBIOTIX, INC",272089,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P21761,1R01AI169850-01A1,Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses,"Project Summary/Abstract Bunyaviruses (Order: Bunyavirales) are a growing and diverse family of animal and human pathogens with pandemic potential. With over 300 members and an expanding distribution of mosquito and tick vectors due to climate change, these viruses are responsible for increasing outbreaks of human disease and present a significant threat to human health. Rift Valley Fever virus (RVFV) is one of the well-studied bunyaviruses and is designated as an NIAID Category A pathogen and included in the WHO’s Blueprint of Priority Diseases. The Coalition for Epidemic Preparedness Innovations (CEPI) included RVFV as part of their emerging infectious diseases vaccine program, further emphasizing the potential impact on the global health and economy. Oropouche virus (OROV) is found in South America and has caused more than 30 large epidemics resulting in over 500,000 human cases, making it the second most common arboviral disease in South America behind Dengue fever. However, the true case number is likely much higher due to Oropouche fever being misdiagnosed as Chikungunya or Dengue. A third member, La Crosse virus (LACV) is found primarily in North America and is the primary cause of pediatric viral encephalitis in the United States. Neither OROV nor LACV have been as well studied as RVFV, and thus a significant gap remains in our broad understanding of bunyavirus pathogenesis. Currently there are no approved therapeutic drugs for treatment of RVFV, OROV, or LACV disease, further highlighting the need for our proposed studies. To address this need, we conducted a genomic screen that defined several critical factors, including Lrp1, an LDL family member. In support we provide compelling preliminary data including in vitro validation in Lrp1 sufficient and deficient cells, transcomplementation studies, and direct interaction between RVFV glycoprotein Gn in vitro. We also show that inhibition of Lrp1 by endogenous ligands in vitro in multiple cell lines from evolutionarily distinct hosts, and in vivo data demonstrating the importance of Lrp1 for viral tropism and disease in mice. Here we will characterize the importance of Lrp1 for entry of multiple bunyaviruses, define molecular mechanisms, and validate the significance in vitro and in vivo. This work will be performed by highly productive and collaborative investigators with expertise in every aspect of the proposed studies, including biochemistry, viral pathogenesis, immunology, proteomics, structural biology, and virology. At completion, we expect to validate Lrp1 as pan-bunyavirus entry factor, filling a key gap in the field and to provide novel targets for therapeutic development.",,2028,Washington University,783556,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21762,1K01AI165965-01A1,Host and Viral Determinants of Orthobunyavirus Vertical Transmission: Novel Model Systems to Understand the Mechanisms of Congenital Disease in Humans and Ruminants,"PROJECT SUMMARY/ABSTRACT Emerging infectious diseases pose a significant threat to human and agricultural health; therefore, it is imperative that we take a proactive approach toward understanding virus and host factors that are associated with infection and pathogenesis. Many bunyavirus infections, including Rift Valley fever (RVFV), Cache Valley (CVV), and Schmallenberg (SBV) viruses, cause massive abortogenic events in livestock that lead to significant economic strain and increased susceptibility of human infection. La Crosse virus (LCV), a related bunyavirus, is not known to cause vertical transmission in livestock, however vertical transmission has been implicated upon experimental infection. Two cases of vertical transmission of RVFV have occurred in pregnant women and those infected with RVFV have a higher risk for late-term miscarriages. Whether vertical transmission occurs in ruminants and humans due to LACV infection or in humans from SBV and CVV infection is unknown. Given LACV and CVV infections can cause life-threatening diseases in humans, it is plausible that congenital infection may simply be overlooked due to the mild nature of most bunyavirus infections. We hypothesize that SBV, CVV, and LACV can infect human and ruminant placentas and that virulence factors, such as NSm, and variable induction of antiviral responses across viruses dictate pathogenesis severity, and thus teratogenicity, across host species. This proposal will utilize two model systems to study bunyavirus infection of the placenta. First, we will examine whether LACV, CVV, SBV, and RVFV infect placenta explants from humans, sheep, and rats in vitro. Using wild type and NSm knockout viruses, we will identify whether NSm contributes to host or cellular tropism, immune responses to infection, programmed cell death pathways, and congenital pathogenesis. Second, we will utilize genetically tractable 2D human trophoblast and trophoblast organoid (TO) systems to compare cell- specific differences in immune responses and cell death pathways upon bunyavirus infection. This will be the first study to utilize human placenta organoids to study congenital bunyavirus infection. To successfully complete the proposed project, I have developed an exceptional career development plan under the primary mentorship of Dr. Amy Hartman (University of Pittsburgh (U Pitt)) and co-mentors, Drs. Carolyn Coyne (Duke University) and Leonard D’Aiuto (U Pitt). My training will consist of hands-on and didactic training in human organoid development in addition to didactic training in pathology, cross-species placenta biology, and immunology. U Pitt provides the necessary environment to support the proposed research and training through accessibility to outstanding scientists, high containment laboratory and animal facilities, training opportunities in laboratory management, responsible conduct of research and grantsmanship, and opportunities to present research. Successful training and completion of the proposed research will support my ultimate career goal to establish an independent research program studying the cross virus- and host-species mechanisms of bunyavirus congenital infections with a special niche in human and ruminant placenta organoid research and congenital pathology.",,2028,University Of Pittsburgh At Pittsburgh,124838,Animals | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Other,,,,,,,,,Rift Valley Fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P21763,5U01AI151758-04,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.",,2025,INSTITUT PASTEUR,1294249,Human Populations | Disease Vectors | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Disease surveillance & mapping",2020 +P21764,1R01AI178378-01,Mechanisms of Neuronal Infection by Prototype Emerging Bunyaviruses,"PROJECT SUMMARY/ABSTRACT Bunyaviruses are a diverse group of animal and human pathogens of global health relevance. Bunyavirales order encompasses viral families with similar genome and protein organization despite divergent sequences. Common to these vector-borne viruses is the ability to cause central nervous system (CNS) disease with concomitant morbidity and occasional mortality. Lack of definition of key target cells in the brain and the effect of virus infection on the brain microenvironment are major limitations in our knowledge of bunyavirus neuropathogenesis that has also limited our ability to develop countermeasures. The consequences of target cell infection are unknown, and viral determinants of neurologic disease have not been delineated. To overcome this limitation, we propose a comparative analysis of the neuropathogenesis of 3 medically important prototype emerging bunyaviruses and define contributors to infection and pathogenesis in relevant neuronal cells. La Crosse virus (LACV) is found in North America and is the primary cause of pediatric viral encephalitis in the United States. Rift Valley Fever virus (RVFV), a WHO Priority Disease, causes outbreaks of hemorrhagic fever and encephalitis throughout Africa. Oropouche virus (OROV), is found in South America and has caused more than 30 large epidemics resulting in over 500,000 human cases of febrile illness. Due lack of direct comparisons, substantial gaps remain in our understanding of bunyavirus neuropathogenesis, including molecular mechanisms. This proposal will provide comparative analysis of all 3 viruses with regards to CNS cell tropism, innate immune responses, and cell death pathways using novel in vitro and ex vivo model systems. Our recently published data shows that the host cell protein LDL-receptor related protein 1 (Lrp1) is important for efficient cellular infection by RVFV and OROV. Preliminary data on the role of Lrp1 in LACV infection further supports similar tropisms by divergent viruses. We hypothesize that these neurovirulent viruses share overlapping target cells in the CNS mediated by the host cell protein Lrp1. Viral non-structural protein produced from the small genome segment (NSs) functions as the main antagonist of host cell antiviral responses and a key modulator during infection. We further hypothesize that the degree of neurovirulence of each virus is related to NSs protein function. Our highly collaborative and synergistic team is led by Dr. Amy Hartman (PI), an expert in the pathogenesis of RVFV and Dr. Gaya Amarasinghe (Co-I), a biochemist with expertise in host-pathogen interactions. Two additional Co-I’s are Dr. Leonard D’Aiuto and Dr. Zachary Wills, are experts in viral infection of human neurons and rodent neurobiology, respectively. This R01 proposal represents a multidisciplinary approach to advance our understanding of bunyavirus interactions with neurons.",,2027,University Of Pittsburgh At Pittsburgh,772395,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P21765,5R35GM138199-04,Uncovering and harnessing connected metabolic pathways essential to virus infection.,"Project Summary / Abstract Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation. While these molecules are important for cellular function, emerging evidence suggests that polyamine metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses (Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus families subvert cellular metabolism, specifically through polyamines, to support virus replication. Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to support virus replication. We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three evolutionarily distant viruses with different replicative and structural differences. While each of these viruses relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure, cellular attachment, and genome replication. We will also use these model systems to understand how these viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways and how viruses rely on these interconnected pathways for successful replication. This work will highlight fundamental roles for polyamines in virus replication and in cellular metabolism.",,2025,Loyola University Chicago,369351,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21766,5R00AI153464-04,Understanding the Molecular Determinants of Reassortment in Orthobunyaviruses and Phleboviruses.,"Project Summary/Abstract Genome reassortment drives the diversity we see in segmented RNA viruses. Unlike recombination, intact genes are readily exchanged between two co-infecting viruses, resulting in their rapid evolution. Reassortment amongst influenza viruses is a well-established driver of host range and virulence. Though reassortment occurs frequently amongst bunyaviruses and can result in highly virulent reassortants such as Ngari virus, the underlying mechanisms are unknown. Understanding how these viruses reassort and modify virulence will allow us to predict potential virus emergence or modulations in host range allowing potential species jumps. The goal of this project is to investigate the molecular determinants of reassortment and virulence amongst orthobunyaviruses and phleboviruses. These are tri-segmented negative sense RNA viruses with Small (S), Medium (M) and Large (L) segments encoding the nucleocapsid protein, glycoproteins GnGc and a viral polymerase (L protein), respectively. Some viruses also encode nonstructural proteins on the S and/or M segments. Aim 1, will investigate segment compatibility amongst the priority pathogens Severe fever with thrombocytopenia syndrome virus and Heartland virus, using a forward and reverse genetics approach. Aim 2, will investigate homologous and heterologous segment dynamics within infected cells. Aim 3, will investigate the virulence of natural reassortants of Oropouche virus and potential reassortants of SFTSV and HRTV. These studies are of significant importance, as only by understanding the fundamental aspects of the biology of these viruses will we be able to understand the molecular determinants of their reassortment. This proposal will support my long-term career goal of understanding novel virus emergence and evolution. My mentorship team consists of Professor Paul Duprex, an expert in paramyxoviruses and cross-species viral transmission, Dr. Anita McElroy, an expert in Rift Valley fever virus (RVFV) transmission and immunology, Dr. Amy Hartman, an expert in RVFV pathogenesis in rats and monkeys and Dr. Seema Lakdawala, an expert in influenza virus biology and reassortment. With the support of strong mentors and collaborators I will receive training in the skills required to complete the proposed aims. Upon completion of the K99 phase I will be in a strong position to pursue an independent and successful research position contributing to the bunyavirus field.",,2024,INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS,249000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21767,5R01AI161765-02,Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis,"Project Summary/Abstract Rift Valley fever virus (RVFV) is a phlebovirus that belongs to the Phenuiviridae (formerly Bunyaviridae) family of negative-sense RNA viruses. As an emerging mosquito-borne virus, the significance of RVFV is highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of Priority Diseases. Recently, the Coalition for Epidemic Preparedness Innovations (CEPI) has also included RVFV as a part of their emerging infectious diseases vaccine program, further emphasizing the potential impact of RVFV on the global health and economy. While RVFV is endemic throughout sub-Saharan Africa, competent mosquito vector species are found in North America, highlighting the potential for emergence of RVFV in non-endemic countries, including the United States. During outbreaks, RVFV causes severe disease in livestock, including sheep and cattle, which dramatically impact the socioeconomic framework in resource limited settings. Humans are spill- over hosts, where infections can result in severe consequences, including hepatic necrosis, hemorrhagic fever, encephalitis, and retinal vasculitis. Despite its significance to human health and the potential to negatively impact the socioeconomic fabric of resource-limited countries where the virus is endemic, there is a lack of safe and efficacious prophylactic and therapeutic treatment options. This gap is in part due to our lack of knowledge on host factors that contribute to RVFV infection. To address this need, we conducted a genomic screen that defined several critical factors, including a potential entry factor, which we will characterize by a multidisciplinary approach. In support, we provide compelling preliminary data, including in vitro validation in host factor sufficient and deficient cells, transcomplementation studies, direct interaction between RVFV glycoprotein Gn and the host proteins in vitro, inhibition of the entry factor by endogenous ligands in vitro in multiple cell lines from evolutionarily distinct hosts, and preliminary results of protection from RVFV infection in two conditional knock out mouse models. Importantly, we have generated many key reagents, including most cell lines and proteins, and knock-out mice supporting the feasibility. Importantly, this work will be performed by highly productive and collaborative investigators with expertise in every aspect of the proposed studies, including biochemistry, RVFV pathogenesis, immunology, proteomics, structural biology, and virology. Completion of the proposed studies will define novel host or entry factors for RVFV in target cells with tissue-specific relevance. As a specific receptor for RVFV has not previously been identified, these studies will provide important information for design of therapeutic interventions to prevent RVFV infection and disease. At the completion, we expect to fill a key gap in the field and to provide novel targets for therapeutic development.",,2026,Washington University,742007,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21768,1R01AI171200-01,Innate immune recognition and response to Rift Valley fever virus,"Rift Valley fever virus (RVFV) is widespread throughout the entire African continent and in some endemic areas over 50% of the population is exposed by adulthood. Antiviral responses induced by interferon (IFN) signaling can limit RVFV replication and inhibit RVFV pathogenesis in vivo. RVFV is known to infect mononuclear phagocytic cells (MPCs), hepatocytes, and neurons, consistent with its main clinical manifestations of acute febrile illness, hepatitis, or encephalitis. However, it is largely unknown how each of these cell types recognizes and responds to RVFV infection or how cell type specific innate immune responses modulate viral pathogenesis. The overall objective for this proposal is to determine how the mammalian host innate immune system recognizes and responds to RVFV infection and how this modulates viral pathogenesis. Our central hypothesis is that differential innate immune recognition and response by infected cells modulates viral pathogenesis. To test this hypothesis, we will 1) identify the innate immune sensors and effectors active in biologically relevant human primary cells, 2) define the contribution of key innate immune sensors and effectors in recognition and response to RVFV infection in vivo and 3) define the role of hematopoietic cell infection in RVFV pathogenesis in vivo. The results of this research will define the mechanisms of innate immune recognition and response following RVFV infection. Moreover, it will inform on cell type-specific responses to infection and how virally mediated antagonism of those responses contributes to viral pathogenesis.",,2027,University Of Pittsburgh At Pittsburgh,469526,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P21769,1R41AI165102-01A1,Discovery of Bunyaviral Endonuclease Inhibitors for Antiviral Therapy,"Abstract Segmented negative-sense, single-stranded RNA viruses (sNSVs), which include bunyaviruses, are causative agents of human diseases. Rift Valley Fever Virus (RVFV), a bunyavirus, causes hemorrhagic fever in humans with a case fatality rate of patients developing hemorrhagic fever reaching approximately 50% and has been classified by the NIAID as a Category A Priority Pathogen. RVFV is mosquito-borne, but is also capable of using a wide range of insect vectors with potential to spread to Europe and the Americas. RVFV has the potential to cause significant global health and economic impact. Unfortunately, there are no FDA-approved drugs or vaccines for the treatment of the RVFV infection. Therefore, there is an urgent medical need for more potent therapeutics tailored for RVFV. The overall goal of this project is to identify and develop small molecule prophylactics and/or therapeutics for RVFV infections and preferably also for infections of other highly related bunyaviruses. The strategy is to address the unmet medical need by identifying small molecule inhibitors targeting the enzymatic activity of the essential RVFV endonuclease, which exhibits significant structural similarity to other sNSV endonucleases. The approach is to leverage the team’s experience with bunyaviral endonucleases and a homogeneous FRET-based biochemical assay to identify small molecules that inhibit the enzymatic activity of bunyaviral endonucleases. In Preliminary Studies, we developed a FRET-endonuclease activity (FRET-EA) assay for RVFV endonuclease and applied the assay in a low/medium-throughput format with Z’-factors ≥0.9. The FRET assay confirmed the inhibition of an FDA approved antiviral to treat Influenza virus (IAV), Baloxavir acid (BXA), against IAV endonuclease. In Phase I, for Aim 1, the FRET-EA assay will be optimized for high-throughput screening. Biochemical and cellular secondary assays, including FRET, thermal shift, and cell-based infectious assays, will be optimized to further evaluate confirmed hits. In Aim 2, the FRET- EA HTS will be applied to diverse chemical libraries of ≥250,000 small molecules for the identification and confirmation of small molecules that inhibit the enzymatic activity of RVFV endonuclease. In Aim 3, hits identified in Aim 2 will be validated in secondary assays for binding to endonuclease, anti-sNSV spectrum, and potency against infectious RVFV. They will also be prioritized based on their drug-likeness and their ADME properties. In Phase II, we will perform structural based mechanism studies and further chemically optimize priority inhibitors for potency, selectivity, in vitro and in vivo pharmacokinetics properties and evaluate them in animal infection models.",,2024,"MICROBIOTIX, INC",296536,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P21770,1R56AI171920-01,Comparative Analysis of Bunyavirus Neuropathogenesis,"PROJECT SUMMARY/ABSTRACT Bunyaviruses are a large, diverse group of vector-borne viruses with the capacity to cause neurological disease with morbidity and mortality. A major limitation in our basic scientific understanding of bunyavirus neuropathogenesis stems from the fact that key target cells in the brain are not fully defined, therefore the effect of infection on target cells is unknown, and viral determinants that contribute to neurological disease have not been delineated. A broader, understanding of how bunyaviruses interact with the central nervous system (CNS), including molecular mechanisms of host-viral interactions, is fundamental for future goal of mitigating effects of disease and long-term sequelae in survivors. Here, we propose a comparative analysis of the basic neuropathogenesis of 3 important emerging bunyaviruses: Rift Valley fever (RVFV), Oropouche (OROV), and La Crosse (LACV). Infection by each of these viruses have the potential to cause significant neurological disease in humans. However, substantial gaps remain in our understanding of bunyavirus neuropathogenesis, including molecular mechanisms that contribute to disease. A limitation is the lack of rigor of prior research is that published studies on these viruses as they are difficult to directly compare due to use of different in vitro cell systems and disparate mouse models, including variations in age and infection route. We will address this gap by directly comparing CNS cell tropism, innate responses, and cell death pathways induced by RVFV, OROV, and LACV using novel in vitro and ex vivo model systems. Given the potential for diverse bunyaviruses to cause neurological sequelae in a subset of human cases, and the fact that all 3 are lethal in neurological mouse models, we hypothesize that diverse bunyaviruses have common target cells in the CNS and that neuronal infection is mediated by Lrp1, a newly identified host entry factor for RVFV. A key feature of bunyaviral virology is the expression of the viral non-structural protein produced from the small genome segment (NSs). NSs is the main antagonist of host cell antiviral responses. Each virus expresses a different NSs protein, and thus we further hypothesize that the degree of neurovirulence of each virus is directly related to NSs protein function, with RVFV NSs being the most potent inhibitor of innate responses. Our highly collaborative and synergistic team is led by Dr. Amy Hartman (PI), an expert in the pathogenesis of RVFV, Dr. Anita McElroy (Co-I), a molecular virologist and immunologist with expertise in emerging viral diseases, Dr. Gaya Amarasinghe (Co-I), a biochemist with expertise in host-pathogen interactions. Two additional Co-I’s are Dr. Leonard D’Aiuto and Dr. Zachary Wills, who are experts in viral infection of human neurons and rodent neurobiology, respectively. This R01 proposal represents a multidisciplinary approach to advance our understanding of bunyavirus interactions with the brain.",,2024,University Of Pittsburgh At Pittsburgh,1149175,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21771,5U01AI151758-03,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.",,2025,INSTITUT PASTEUR,1287136,Human Populations | Disease Vectors | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Animal source and routes of transmission | Disease surveillance & mapping",2020 +P21772,5R35GM138199-03,Uncovering and harnessing connected metabolic pathways essential to virus infection.,"Project Summary / Abstract Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation. While these molecules are important for cellular function, emerging evidence suggests that polyamine metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses (Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus families subvert cellular metabolism, specifically through polyamines, to support virus replication. Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to support virus replication. We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three evolutionarily distant viruses with different replicative and structural differences. While each of these viruses relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure, cellular attachment, and genome replication. We will also use these model systems to understand how these viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways and how viruses rely on these interconnected pathways for successful replication. This work will highlight fundamental roles for polyamines in virus replication and in cellular metabolism.",,2025,Loyola University Chicago,369351,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21773,4R00AI153464-03,Understanding the Molecular Determinants of Reassortment in Orthobunyaviruses and Phleboviruses.,"Project Summary/Abstract Genome reassortment drives the diversity we see in segmented RNA viruses. Unlike recombination, intact genes are readily exchanged between two co-infecting viruses, resulting in their rapid evolution. Reassortment amongst influenza viruses is a well-established driver of host range and virulence. Though reassortment occurs frequently amongst bunyaviruses and can result in highly virulent reassortants such as Ngari virus, the underlying mechanisms are unknown. Understanding how these viruses reassort and modify virulence will allow us to predict potential virus emergence or modulations in host range allowing potential species jumps. The goal of this project is to investigate the molecular determinants of reassortment and virulence amongst orthobunyaviruses and phleboviruses. These are tri-segmented negative sense RNA viruses with Small (S), Medium (M) and Large (L) segments encoding the nucleocapsid protein, glycoproteins GnGc and a viral polymerase (L protein), respectively. Some viruses also encode nonstructural proteins on the S and/or M segments. Aim 1, will investigate segment compatibility amongst the priority pathogens Severe fever with thrombocytopenia syndrome virus and Heartland virus, using a forward and reverse genetics approach. Aim 2, will investigate homologous and heterologous segment dynamics within infected cells. Aim 3, will investigate the virulence of natural reassortants of Oropouche virus and potential reassortants of SFTSV and HRTV. These studies are of significant importance, as only by understanding the fundamental aspects of the biology of these viruses will we be able to understand the molecular determinants of their reassortment. This proposal will support my long-term career goal of understanding novel virus emergence and evolution. My mentorship team consists of Professor Paul Duprex, an expert in paramyxoviruses and cross-species viral transmission, Dr. Anita McElroy, an expert in Rift Valley fever virus (RVFV) transmission and immunology, Dr. Amy Hartman, an expert in RVFV pathogenesis in rats and monkeys and Dr. Seema Lakdawala, an expert in influenza virus biology and reassortment. With the support of strong mentors and collaborators I will receive training in the skills required to complete the proposed aims. Upon completion of the K99 phase I will be in a strong position to pursue an independent and successful research position contributing to the bunyavirus field.",,2024,INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS,249000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21775,3G20AI167408-01S1,Administrative Supplements for NIAID Regional Biocontainment Laboratories (RBL),"Project Summary/Abstract: The ongoing COVID pandemic has demonstrated the need for state-of-the-art facilities and infrastructure to improve our preparedness for subsequent epidemics and/or pandemics. George Mason University (GMU), leveraging the Regional Biocontainment Laboratory, designated as the Biomedical Research Laboratory (BRL), has established a biomedical research program with a strong emphasis on newly emerging and re- emerging viral and bacterial pathogens with the potential to cause severe human and animal diseases. The specific viral pathogen families of greatest pandemic concern currently investigated in the BRL are: Togaviridae, Bunyaviridae, Coronaviridae, and Flaviviridae. Several faculty members in five departments at GMU (Systems Biology, Biology, Bioengineering, Biochemistry, and Global and Community Health) as well as external collaborators conduct research on basic and applied research to include pathogenicity, infection mechanisms, and development of diagnostics, vaccines and therapeutics. The infectious disease portfolio at GMU was $8.8 million in FY21 and is expected to grow by at least 3X in the next five years. To realize this goal, GMU leadership is making aggressive, strategic investments in new faculty hires and seed funding, as well as creating broader access to the BRL. More than 244 peer-reviewed articles on infectious diseases research have been published by GMU investigators since 2010. The BRL staff is dedicated to supporting GMU faculty, students, and their collaborators to develop new translational solutions for pandemic preparedness. Research with translational promise includes 1) development of additional vaccine candidates that confer broad-spectrum protection against multiple strains of alphaviruses or coronaviruses, 2) evaluation of host-based therapeutics that have demonstrated in vitro broad- spectrum efficacy against alphaviruses (VEEV, EEEV, WEEV, CHIKV), bunyaviruses (RVFV) and coronaviruses (SARS-CoV-2) in rodent and nonrodent animal models including ferrets, and 3) development of new platform technologies including extracellular vesicle (EV)-based immunomodulators and reporter viruses that can facilitate rapid screening of clinical and nonclinical samples for neutralizing antibodies. Our high containment facility supported by a team of operations and technical staff, creates opportunities for a broad base of internal and external investigators to conduct in vitro and in vivo research and development on newly emerging and re-emerging viral and bacterial pathogens. GMU is requesting funds to supplement the funded G20 parent award, “Facility and Building System Upgrades Support for the Mason Biomedical Research Laboratory” to resolve additional specific instrumentation and facility gaps that will support the creation of a modern, comprehensive, agile and resilient preclinical biomedical research pipeline to address national and global pandemic preparedness.",,2025,George Mason University,4039853,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Coronavirus | Flaviviridae,,,,,,,,,Rift Valley Fever | COVID-19 | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics | Pre-clinical studies | Pre-clinical studies,2021 +P21776,1R01AI161765-01,Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis,"Project Summary/Abstract Rift Valley fever virus (RVFV) is a phlebovirus that belongs to the Phenuiviridae (formerly Bunyaviridae) family of negative-sense RNA viruses. As an emerging mosquito-borne virus, the significance of RVFV is highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of Priority Diseases. Recently, the Coalition for Epidemic Preparedness Innovations (CEPI) has also included RVFV as a part of their emerging infectious diseases vaccine program, further emphasizing the potential impact of RVFV on the global health and economy. While RVFV is endemic throughout sub-Saharan Africa, competent mosquito vector species are found in North America, highlighting the potential for emergence of RVFV in non-endemic countries, including the United States. During outbreaks, RVFV causes severe disease in livestock, including sheep and cattle, which dramatically impact the socioeconomic framework in resource limited settings. Humans are spill- over hosts, where infections can result in severe consequences, including hepatic necrosis, hemorrhagic fever, encephalitis, and retinal vasculitis. Despite its significance to human health and the potential to negatively impact the socioeconomic fabric of resource-limited countries where the virus is endemic, there is a lack of safe and efficacious prophylactic and therapeutic treatment options. This gap is in part due to our lack of knowledge on host factors that contribute to RVFV infection. To address this need, we conducted a genomic screen that defined several critical factors, including a potential entry factor, which we will characterize by a multidisciplinary approach. In support, we provide compelling preliminary data, including in vitro validation in host factor sufficient and deficient cells, transcomplementation studies, direct interaction between RVFV glycoprotein Gn and the host proteins in vitro, inhibition of the entry factor by endogenous ligands in vitro in multiple cell lines from evolutionarily distinct hosts, and preliminary results of protection from RVFV infection in two conditional knock out mouse models. Importantly, we have generated many key reagents, including most cell lines and proteins, and knock-out mice supporting the feasibility. Importantly, this work will be performed by highly productive and collaborative investigators with expertise in every aspect of the proposed studies, including biochemistry, RVFV pathogenesis, immunology, proteomics, structural biology, and virology. Completion of the proposed studies will define novel host or entry factors for RVFV in target cells with tissue-specific relevance. As a specific receptor for RVFV has not previously been identified, these studies will provide important information for design of therapeutic interventions to prevent RVFV infection and disease. At the completion, we expect to fill a key gap in the field and to provide novel targets for therapeutic development.",,2026,Washington University,756494,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21777,5R21AI148896-02,Transstadial inhibition of Rift Valley Fever virus infection in Ae. aegypti mosquitoes,"Project Summary Rift Valley fever virus (RVFV) (Phenuiviridae: Phlebovirus) is an emerging mosquito-transmitted virus with a high probability of introduction to new areas, including the United States. Significant questions remain regarding the inter-epidemic maintenance of RVFV in endemic countries, and the ecological importance of North American mosquitoes in the establishment and transmission of RVFV. In particular, RVFV is currently believed to be maintained in natural mosquito vector populations through vertical transmission, however published laboratory evidence documenting this phenomenon is completely lacking. We recently demonstrated high RVFV dissemination rates and infection of ovarian tissues in both Ae. aegypti and Cx. tarsalis mosquitoes orally exposed to an epidemic strain of RVFV from Kenya. The infection rate of the 1st instar larvae of Cx. tarsalis mosquitoes was 87% (Bergren, preliminary data). This is the first time transovarial transmission of RVFV has been experimentally demonstrated in any mosquito species. Interestingly, transstadial transmission of RVFV from eggs to F1 adult life stages was inhibited in Ae. aegypti due to an unknown mechanism. This project will address the hypotheses that the efficiency of transstadial transmission of RVFV is mediated by larval habitat temperature (Aim 1), as well as mosquito anti-viral effectors and Wnt signalling during immature developmental stages (Aim 2). For Aim 1, both Cx. tarsalis and Ae. aegypti mosquitoes derived from RVFV- infected parental mosquitoes will be reared at low (18Ã'°C) standard (28Ã'°C), and high (35Ã'°C) temperatures. Transstadial virus persistence in each mosquito species will be quantified by qRT-PCR and plaque titration of 1st instar, 4th instar, pupal, and F1 adult mosquitoes reared at each temperature. Statistical analysis of infection rates as well as virus titer in each life stage as a function of mosquito species and temperature will inform whether or not larval rearing temperature significantly influences transstadial persistence of RVFV. To support these environmental data, RNA-Seq will be employed in Aim 2 to identify the underlying molecular pathways contributing to our preliminary phenotypic observations. Differential gene expression will be analyzed in individual mosquitoes of each species throughout the developmental process. The function of top-candidate genes during RVFV transstadial transmission will be confirmed by specific double-stranded RNA knock-down in mosquito larvae. The data generated in these studies will collectively elucidate environmental and molecular drivers of RVFV persistence in North American mosquito populations. This project will also directly address shortcomings in current predictive models regarding the environmental persistence and establishment potential of RVFV in mosquitoes.",,2022,Colorado State University,228000,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector biology",2020 +P21778,5R21AI148763-02,Mechanism of viral RNP recognition by the envelope glycoprotein and its role in RNA segment packaging in Rift Valley Fever phlebovirus,"Rift Valley fever Phlebovirus (RVFV), a bunyavirus, belongs to the NIAID Category A list of pathogens and the CDC list of potential bioterrorism agents. RVFV causes a disease that is endemic in sub-Saharan Africa and can emerge in explosive, mosquito-borne epidemics that decimate herds of sheep and cattle, resulting in enormous economic losses. In humans, RVFV infection may cause hemorrhagic fever, encephalitis, and retinal vasculitis. Many different mosquitoes, including several species native to North America, are competent vectors for RVFV transmission. The introduction of RVFV into North America would likely cause panic in the general population, and the effects on livestock could have a devastating economic impact. The lack of availability of licensed vaccines or anti-RVFV reagents for use in humans or domestic animals is of great concern. RVFV carries a tripartite, single-stranded, negative-sense RNA genome, including L RNA encoding L protein, M RNA encoding two major envelope glycoproteins, Gn and Gc, and S RNA encoding N and NSs. NSs is the major virulence factor that efficiently suppresses host antiviral responses. The S RNA uses an ambi-sense strategy for gene expression; NSs is translated from the mRNA that is transcribed from the antigenomic-sense S RNA, whereas N protein is produced from the mRNA that is transcribed from the genomic-sense S RNA. One of the essential steps in virus replication and dissemination is the packaging of viral genome into virus particles, however, the mechanisms of viral RNA packaging in RVFV and other bunyaviruses are largely unknown. Insight into the underlying rules and mechanisms that govern the packaging of viral RNA genome into RVFV particles is valuable for understanding the regulation of virus replication, virus evolution, and the pathogenesis of the virus. This knowledge is also critical for the development of antiviral drugs that can inhibit infectious virus production or for the development of a live- attenuated vaccine strain. We propose that a direct interaction of Gn with the viral RNA segments is the primary factor that influences the packaging efficiencies of viral RNAs into RVFV particles. The present application will clarify the mechanism and biological significance of efficient packaging of antigenomic S RNA into virus particles by characterizing the direct interaction of Gn with antigenomic S RNA, identify the Gn- binding sites in viral RNAs, and examine the importance of antigenomic S RNA packaging for RVFV replication. The data obtained from the proposed studies will clarify the fundamental mechanisms that drive viral RNA packaging in RVFV and other bunyaviruses, with the overall goal of informing the design of novel antivirals and vaccines.",,2023,University Of Texas Med Br Galveston,197500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P21779,5R21AI128377-03,Identification of Small Molecular Inhibitors of Rift Valley Fever Virus Replication,"Project Summary Rift Valley fever caused by Rift Valley fever virus (RVFV) is an acute, mosquito-borne, fever-causing zoonotic disease that affects both humans and animals. Large Rift Valley fever outbreaks have occurred throughout Africa and more recently in the Arabian Peninsula. Because RVFV is no longer restricted to African countries, it has raised concerns that the disease could spread worldwide. The RVFV is a select agent that requires high biocontainment facilities. This limitation has hampered the development of RVFV antivirals and vaccines. Despite the significant impact of the disease to the economy and public health, there are no fully licensed vaccine and antivirals available in the US for human and animal use. It is urgent to identify and develop effective inhibitors against RVFV to treat exposed and infected humans and animals. Dr. Ma’s group has developed a cell-based screening assay based on the RVFV MP12 vaccine strain that expresses Renilla Luciferase using Renilla as readout to identify RVFV inhibitors, and established a STAT1-KO mouse model susceptible to infection with MP12 vaccine strain that can be used in a BSL-2 facility. Furthermore, they have screened 727 compounds from the NIH collections of which two candidates including 6-azauridine and mitoxantrone inhibited replication of MP12. They hypothesize that effective inhibitors against RVFV can be identified by screening large compound collections and by further optimization of their structures and activities, and the mechanisms of inhibitory effects of identified candidates can be determined. Thus, they plan to use the developed high-throughput assay to identify inhibitors against RVFV, evaluate their efficacy in vitro and in mice, and understand the underlying mechanisms of inhibitory effects of identified candidates through two specific aims in this R21 proposal. In specific aim 1, the libraries assembled by the University of Kansas High Throughput Screening Laboratory that contain approximately 26,000 chemical compounds will be screened. The 26,000 compounds are predicted to cross the blood-brain barrier. Hits from the library will help overcome the challenge for RVFV antivirals to reach the brain through the blood-brain barrier to protect encephalitis. Primary hits will be confirmed by in vitro and in vivo assays. In specific aim 2, 6-azauridine and mitoxantrone as well as others identified in Aim 1 will be evaluated in vitro and in the BALB/c mice using virulent RVFV. To understand the underlying mechanisms of their inhibitory effects, whether the compounds block virus entry, inhibit virus replication and polymerase activity will be investigated using different designed assays. The results of this study could identify novel effective inhibitors against RVFV and understand the underlying mechanisms of their inhibitory effects, and offer novel insights toward the design of novel antiviral drugs against this zoonotic disease that will benefit both human and animal health.",,2023,University Of Missouri-Columbia,182360,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21780,5U01AI151758-02,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.",,2025,INSTITUT PASTEUR,1213204,Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Disease surveillance & mapping",2020 +P21781,5R35GM138199-02,Uncovering and harnessing connected metabolic pathways essential to virus infection.,"Project Summary / Abstract Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation. While these molecules are important for cellular function, emerging evidence suggests that polyamine metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses (Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus families subvert cellular metabolism, specifically through polyamines, to support virus replication. Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to support virus replication. We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three evolutionarily distant viruses with different replicative and structural differences. While each of these viruses relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure, cellular attachment, and genome replication. We will also use these model systems to understand how these viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways and how viruses rely on these interconnected pathways for successful replication. This work will highlight fundamental roles for polyamines in virus replication and in cellular metabolism.",,2025,Loyola University Chicago,369351,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21782,5K99AI153464-02,Understanding the Molecular Determinants of Reassortment in Orthobunyaviruses and Phleboviruses.,"Project Summary/Abstract Genome reassortment drives the diversity we see in segmented RNA viruses. Unlike recombination, intact genes are readily exchanged between two co-infecting viruses, resulting in their rapid evolution. Reassortment amongst influenza viruses is a well-established driver of host range and virulence. Though reassortment occurs frequently amongst bunyaviruses and can result in highly virulent reassortants such as Ngari virus, the underlying mechanisms are unknown. Understanding how these viruses reassort and modify virulence will allow us to predict potential virus emergence or modulations in host range allowing potential species jumps. The goal of this project is to investigate the molecular determinants of reassortment and virulence amongst orthobunyaviruses and phleboviruses. These are tri-segmented negative sense RNA viruses with Small (S), Medium (M) and Large (L) segments encoding the nucleocapsid protein, glycoproteins GnGc and a viral polymerase (L protein), respectively. Some viruses also encode nonstructural proteins on the S and/or M segments. Aim 1, will investigate segment compatibility amongst the priority pathogens Severe fever with thrombocytopenia syndrome virus and Heartland virus, using a forward and reverse genetics approach. Aim 2, will investigate homologous and heterologous segment dynamics within infected cells. Aim 3, will investigate the virulence of natural reassortants of Oropouche virus and potential reassortants of SFTSV and HRTV. These studies are of significant importance, as only by understanding the fundamental aspects of the biology of these viruses will we be able to understand the molecular determinants of their reassortment. This proposal will support my long-term career goal of understanding novel virus emergence and evolution. My mentorship team consists of Professor Paul Duprex, an expert in paramyxoviruses and cross-species viral transmission, Dr. Anita McElroy, an expert in Rift Valley fever virus (RVFV) transmission and immunology, Dr. Amy Hartman, an expert in RVFV pathogenesis in rats and monkeys and Dr. Seema Lakdawala, an expert in influenza virus biology and reassortment. With the support of strong mentors and collaborators I will receive training in the skills required to complete the proposed aims. Upon completion of the K99 phase I will be in a strong position to pursue an independent and successful research position contributing to the bunyavirus field.",,2022,University Of Pittsburgh At Pittsburgh,87098,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P21783,1R21AI148896-01,Transstadial inhibition of Rift Valley Fever virus infection in Ae. aegypti mosquitoes,"Project Summary Rift Valley fever virus (RVFV) (Phenuiviridae: Phlebovirus) is an emerging mosquito-transmitted virus with a high probability of introduction to new areas, including the United States. Significant questions remain regarding the inter-epidemic maintenance of RVFV in endemic countries, and the ecological importance of North American mosquitoes in the establishment and transmission of RVFV. In particular, RVFV is currently believed to be maintained in natural mosquito vector populations through vertical transmission, however published laboratory evidence documenting this phenomenon is completely lacking. We recently demonstrated high RVFV dissemination rates and infection of ovarian tissues in both Ae. aegypti and Cx. tarsalis mosquitoes orally exposed to an epidemic strain of RVFV from Kenya. The infection rate of the 1st instar larvae of Cx. tarsalis mosquitoes was 87% (Bergren, preliminary data). This is the first time transovarial transmission of RVFV has been experimentally demonstrated in any mosquito species. Interestingly, transstadial transmission of RVFV from eggs to F1 adult life stages was inhibited in Ae. aegypti due to an unknown mechanism. This project will address the hypotheses that the efficiency of transstadial transmission of RVFV is mediated by larval habitat temperature (Aim 1), as well as mosquito anti-viral effectors and Wnt signalling during immature developmental stages (Aim 2). For Aim 1, both Cx. tarsalis and Ae. aegypti mosquitoes derived from RVFV- infected parental mosquitoes will be reared at low (18Ã'°C) standard (28Ã'°C), and high (35Ã'°C) temperatures. Transstadial virus persistence in each mosquito species will be quantified by qRT-PCR and plaque titration of 1st instar, 4th instar, pupal, and F1 adult mosquitoes reared at each temperature. Statistical analysis of infection rates as well as virus titer in each life stage as a function of mosquito species and temperature will inform whether or not larval rearing temperature significantly influences transstadial persistence of RVFV. To support these environmental data, RNA-Seq will be employed in Aim 2 to identify the underlying molecular pathways contributing to our preliminary phenotypic observations. Differential gene expression will be analyzed in individual mosquitoes of each species throughout the developmental process. The function of top-candidate genes during RVFV transstadial transmission will be confirmed by specific double-stranded RNA knock-down in mosquito larvae. The data generated in these studies will collectively elucidate environmental and molecular drivers of RVFV persistence in North American mosquito populations. This project will also directly address shortcomings in current predictive models regarding the environmental persistence and establishment potential of RVFV in mosquitoes.",,2021,Colorado State University,182447,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector biology",2020 +P21784,7R21AI128377-02,Identification of Small Molecular Inhibitors of Rift Valley Fever Virus Replication,"Project Summary Rift Valley fever caused by Rift Valley fever virus (RVFV) is an acute, mosquito-borne, fever-causing zoonotic disease that affects both humans and animals. Large Rift Valley fever outbreaks have occurred throughout Africa and more recently in the Arabian Peninsula. Because RVFV is no longer restricted to African countries, it has raised concerns that the disease could spread worldwide. The RVFV is a select agent that requires high biocontainment facilities. This limitation has hampered the development of RVFV antivirals and vaccines. Despite the significant impact of the disease to the economy and public health, there are no fully licensed vaccine and antivirals available in the US for human and animal use. It is urgent to identify and develop effective inhibitors against RVFV to treat exposed and infected humans and animals. Dr. Ma’s group has developed a cell-based screening assay based on the RVFV MP12 vaccine strain that expresses Renilla Luciferase using Renilla as readout to identify RVFV inhibitors, and established a STAT1-KO mouse model susceptible to infection with MP12 vaccine strain that can be used in a BSL-2 facility. Furthermore, they have screened 727 compounds from the NIH collections of which two candidates including 6-azauridine and mitoxantrone inhibited replication of MP12. They hypothesize that effective inhibitors against RVFV can be identified by screening large compound collections and by further optimization of their structures and activities, and the mechanisms of inhibitory effects of identified candidates can be determined. Thus, they plan to use the developed high-throughput assay to identify inhibitors against RVFV, evaluate their efficacy in vitro and in mice, and understand the underlying mechanisms of inhibitory effects of identified candidates through two specific aims in this R21 proposal. In specific aim 1, the libraries assembled by the University of Kansas High Throughput Screening Laboratory that contain approximately 26,000 chemical compounds will be screened. The 26,000 compounds are predicted to cross the blood-brain barrier. Hits from the library will help overcome the challenge for RVFV antivirals to reach the brain through the blood-brain barrier to protect encephalitis. Primary hits will be confirmed by in vitro and in vivo assays. In specific aim 2, 6-azauridine and mitoxantrone as well as others identified in Aim 1 will be evaluated in vitro and in the BALB/c mice using virulent RVFV. To understand the underlying mechanisms of their inhibitory effects, whether the compounds block virus entry, inhibit virus replication and polymerase activity will be investigated using different designed assays. The results of this study could identify novel effective inhibitors against RVFV and understand the underlying mechanisms of their inhibitory effects, and offer novel insights toward the design of novel antiviral drugs against this zoonotic disease that will benefit both human and animal health.",,2022,University Of Missouri-Columbia,200337,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21785,1R21AI148763-01A1,Mechanism of viral RNP recognition by the envelope glycoprotein and its role in RNA segment packaging in Rift Valley Fever phlebovirus,"Rift Valley fever Phlebovirus (RVFV), a bunyavirus, belongs to the NIAID Category A list of pathogens and the CDC list of potential bioterrorism agents. RVFV causes a disease that is endemic in sub-Saharan Africa and can emerge in explosive, mosquito-borne epidemics that decimate herds of sheep and cattle, resulting in enormous economic losses. In humans, RVFV infection may cause hemorrhagic fever, encephalitis, and retinal vasculitis. Many different mosquitoes, including several species native to North America, are competent vectors for RVFV transmission. The introduction of RVFV into North America would likely cause panic in the general population, and the effects on livestock could have a devastating economic impact. The lack of availability of licensed vaccines or anti-RVFV reagents for use in humans or domestic animals is of great concern. RVFV carries a tripartite, single-stranded, negative-sense RNA genome, including L RNA encoding L protein, M RNA encoding two major envelope glycoproteins, Gn and Gc, and S RNA encoding N and NSs. NSs is the major virulence factor that efficiently suppresses host antiviral responses. The S RNA uses an ambi-sense strategy for gene expression; NSs is translated from the mRNA that is transcribed from the antigenomic-sense S RNA, whereas N protein is produced from the mRNA that is transcribed from the genomic-sense S RNA. One of the essential steps in virus replication and dissemination is the packaging of viral genome into virus particles, however, the mechanisms of viral RNA packaging in RVFV and other bunyaviruses are largely unknown. Insight into the underlying rules and mechanisms that govern the packaging of viral RNA genome into RVFV particles is valuable for understanding the regulation of virus replication, virus evolution, and the pathogenesis of the virus. This knowledge is also critical for the development of antiviral drugs that can inhibit infectious virus production or for the development of a live- attenuated vaccine strain. We propose that a direct interaction of Gn with the viral RNA segments is the primary factor that influences the packaging efficiencies of viral RNAs into RVFV particles. The present application will clarify the mechanism and biological significance of efficient packaging of antigenomic S RNA into virus particles by characterizing the direct interaction of Gn with antigenomic S RNA, identify the Gn- binding sites in viral RNAs, and examine the importance of antigenomic S RNA packaging for RVFV replication. The data obtained from the proposed studies will clarify the fundamental mechanisms that drive viral RNA packaging in RVFV and other bunyaviruses, with the overall goal of informing the design of novel antivirals and vaccines.",,2022,University Of Texas Med Br Galveston,237000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21786,1R21AI128377-01A1,Identification of Small Molecular Inhibitors of Rift Valley Fever Virus Replication,"Project Summary Rift Valley fever caused by Rift Valley fever virus (RVFV) is an acute, mosquito-borne, fever-causing zoonotic disease that affects both humans and animals. Large Rift Valley fever outbreaks have occurred throughout Africa and more recently in the Arabian Peninsula. Because RVFV is no longer restricted to African countries, it has raised concerns that the disease could spread worldwide. The RVFV is a select agent that requires high biocontainment facilities. This limitation has hampered the development of RVFV antivirals and vaccines. Despite the significant impact of the disease to the economy and public health, there are no fully licensed vaccine and antivirals available in the US for human and animal use. It is urgent to identify and develop effective inhibitors against RVFV to treat exposed and infected humans and animals. Dr. Ma’s group has developed a cell-based screening assay based on the RVFV MP12 vaccine strain that expresses Renilla Luciferase using Renilla as readout to identify RVFV inhibitors, and established a STAT1-KO mouse model susceptible to infection with MP12 vaccine strain that can be used in a BSL-2 facility. Furthermore, they have screened 727 compounds from the NIH collections of which two candidates including 6-azauridine and mitoxantrone inhibited replication of MP12. They hypothesize that effective inhibitors against RVFV can be identified by screening large compound collections and by further optimization of their structures and activities, and the mechanisms of inhibitory effects of identified candidates can be determined. Thus, they plan to use the developed high-throughput assay to identify inhibitors against RVFV, evaluate their efficacy in vitro and in mice, and understand the underlying mechanisms of inhibitory effects of identified candidates through two specific aims in this R21 proposal. In specific aim 1, the libraries assembled by the University of Kansas High Throughput Screening Laboratory that contain approximately 26,000 chemical compounds will be screened. The 26,000 compounds are predicted to cross the blood-brain barrier. Hits from the library will help overcome the challenge for RVFV antivirals to reach the brain through the blood-brain barrier to protect encephalitis. Primary hits will be confirmed by in vitro and in vivo assays. In specific aim 2, 6-azauridine and mitoxantrone as well as others identified in Aim 1 will be evaluated in vitro and in the BALB/c mice using virulent RVFV. To understand the underlying mechanisms of their inhibitory effects, whether the compounds block virus entry, inhibit virus replication and polymerase activity will be investigated using different designed assays. The results of this study could identify novel effective inhibitors against RVFV and understand the underlying mechanisms of their inhibitory effects, and offer novel insights toward the design of novel antiviral drugs against this zoonotic disease that will benefit both human and animal health.",,2020,Kansas State University,43034,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P21787,1U01AI151758-01,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.",,2025,INSTITUT PASTEUR,1186205,Human Populations | Disease Vectors | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Immunity | Disease surveillance & mapping",2020 +P21788,1R35GM138199-01,Uncovering and harnessing connected metabolic pathways essential to virus infection.,"Project Summary / Abstract Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation. While these molecules are important for cellular function, emerging evidence suggests that polyamine metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses (Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus families subvert cellular metabolism, specifically through polyamines, to support virus replication. Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to support virus replication. We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three evolutionarily distant viruses with different replicative and structural differences. While each of these viruses relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure, cellular attachment, and genome replication. We will also use these model systems to understand how these viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways and how viruses rely on these interconnected pathways for successful replication. This work will highlight fundamental roles for polyamines in virus replication and in cellular metabolism.",,2025,Loyola University Chicago,368430,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P21789,1K99AI153464-01,Understanding the Molecular Determinants of Reassortment in Orthobunyaviruses and Phleboviruses.,"Project Summary/Abstract Genome reassortment drives the diversity we see in segmented RNA viruses. Unlike recombination, intact genes are readily exchanged between two co-infecting viruses, resulting in their rapid evolution. Reassortment amongst influenza viruses is a well-established driver of host range and virulence. Though reassortment occurs frequently amongst bunyaviruses and can result in highly virulent reassortants such as Ngari virus, the underlying mechanisms are unknown. Understanding how these viruses reassort and modify virulence will allow us to predict potential virus emergence or modulations in host range allowing potential species jumps. The goal of this project is to investigate the molecular determinants of reassortment and virulence amongst orthobunyaviruses and phleboviruses. These are tri-segmented negative sense RNA viruses with Small (S), Medium (M) and Large (L) segments encoding the nucleocapsid protein, glycoproteins GnGc and a viral polymerase (L protein), respectively. Some viruses also encode nonstructural proteins on the S and/or M segments. Aim 1, will investigate segment compatibility amongst the priority pathogens Severe fever with thrombocytopenia syndrome virus and Heartland virus, using a forward and reverse genetics approach. Aim 2, will investigate homologous and heterologous segment dynamics within infected cells. Aim 3, will investigate the virulence of natural reassortants of Oropouche virus and potential reassortants of SFTSV and HRTV. These studies are of significant importance, as only by understanding the fundamental aspects of the biology of these viruses will we be able to understand the molecular determinants of their reassortment. This proposal will support my long-term career goal of understanding novel virus emergence and evolution. My mentorship team consists of Professor Paul Duprex, an expert in paramyxoviruses and cross-species viral transmission, Dr. Anita McElroy, an expert in Rift Valley fever virus (RVFV) transmission and immunology, Dr. Amy Hartman, an expert in RVFV pathogenesis in rats and monkeys and Dr. Seema Lakdawala, an expert in influenza virus biology and reassortment. With the support of strong mentors and collaborators I will receive training in the skills required to complete the proposed aims. Upon completion of the K99 phase I will be in a strong position to pursue an independent and successful research position contributing to the bunyavirus field.",,2022,University Of Pittsburgh At Pittsburgh,87098,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P21790,5R01TW012434-03,Measuring human behavior and ecological dimensions of pathogen transmission for outbreak control and prevention,"This project proposes interdisciplinary research across biology and geography to examine links between human-environment interactions, spatiotemporal patterns of human mobility and health geographies, and endemic and emerging infectious diseases. This work focuses on measles and Ebola prevention and management in the Équateur province in the Democratic Republic of Congo (DRC), where both pathogens cause significant morbidity and mortality. Recurring outbreaks emphasize an urgent need for significant public health improvements. This research investigates the mechanisms underlying pathogen transmission and identifies epidemiological units, across which transmission occurs, and measure their vulnerability to outbreaks. Outputs will be developed with and for mobile health teams in the DRC and will provide a generalizable blueprint for the broader application of this approach across a range of contexts. The proposed research targets the intersection of theoretical frameworks to examine four interlinked topics. First, following Cutter in 2003, this project will develop formal spatial methods to identify and delineate epidemiological units of pathogen transmission and measure their epidemiological vulnerability. Vulnerability is determined by the mechanisms underlying locally specific transmission processes, which differ across diseases. This work includes health data quality as a problem that allow public health problems to persist where they most need improvement. Second, building on Kwan’s 2013 work, this research will start with R1’s epidemiological units and vulnerability indices and integrate the dynamics of seasonal and long-term population mobility, connectivity, and distribution. Population dynamics drive contacts, transmission, and spread for communicable pathogens and must be included in vaccinations and outbreak response. Third, extending Shuurman’s 2011 work, this research will visually represent these dynamic epidemiological units and vulnerability indices cartographically to advance methods in geovisualizations and provide usable spatial decision support systems (SDSS) for mobile health efforts. To maximize clarity and usability, these visualizations will be rigorously developed and tested with our collaborating humanitarian organization’s field teams and graduate students in infectious diseases and geography. Fourth, this work will develop dynamic quantitative models to produce formal comparisons of intervention strategies and iteratively improve them. Models will compare A) strategies using the proposed SDSS, which highlight acting on the vulnerability of epidemiological units of transmission before outbreaks occur for immunizations and outbreak responses and B) the current system, which is guided by administrative boundaries and case rate thresholds to trigger response. Linking spatial and temporal elements of human-environment interactions to support infectious disease prevention and outbreak management will significantly advance the current methods and theory in this field.",,2027,"Pennsylvania State University, The",496367,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease surveillance & mapping | Approaches to public health interventions,2022 +P21795,5R01AI167295-02,Analysis of a novel Crimean-Congo hemorrhagic fever vaccine and its mechanism of protection in rodent models,"Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease in humans, with fatality rates reaching 40%. CCHFV is endemic to parts of Africa, Asia, the Middle East, and Europe, specifically to regions where the tick vector, species of the Hyalomma genus, is present. Classified as an NIH/NIAID Category A and WHO high- priority pathogen, CCHFV poses the highest possible risk to national security and public health. CCHFV is a negative-sense single-stranded RNA virus in the order Bunyavirales. CCHFV is an Emerging Infectious Disease, posing a high risk of a widespread outbreak. An inactivated whole virus vaccine was the only CCHFV vaccine to be tested in humans and was ineffective. We propose the use of inactivated rabies virus (RABV)- and vesicular stomatitis virus (VSV)-based CCHFV vaccines, as inactivated rhabdoviral vectors have not yet been explored. Inactivated rhabdoviral-based vaccines are safe and effective at inducing immunity and protection against multiple hemorrhagic fever viruses, and a VSV-based surrogate challenge virus is an effective tool in another hemorrhagic fever model. The goal of this project is two-fold: first, to compare RABV- and VSV-based CCHFV/RABV bivalent vaccines in terms of their production, immunogenicity; second, to establish a non-BSL-4 VSV-based surrogate mouse challenge system for CCHFV to determine mechanism of protection. We hypothesize that inactivated rhabdoviral-based CCHFV vaccines will protect against the CCHFV challenge through non-neutralizing antibodies directed against GP38. Toward this hypothesis, we propose three Aims: Aim 1: Characterization of Rhabdoviral-based CCHFV vaccine constructs. This aim does characterize and test the immunogenicity of RABV- and VSV-based CCHFV vaccines and compare them to the Bulgaria human vaccine and an mRNA-based vaccine provided by collaborators. Aim 2: Determine rhabdoviral-based CCHFV vaccine mechanism of protection by establishing a surrogate challenge virus model. This aim aims to develop a non-BSL-4-requiring surrogate challenge model for CCHFV and compare it to the established BSL-4 WT CCHFV model in vaccine efficacy studies. Aim 3: Evaluate the protective efficacy of rhabdoviral-based vaccine candidates in a wildtype CCHFV lethal challenge model using needle and tick challenge. The goal of this aim is to determine the efficacy of our rhabdoviral-based vaccines and control vaccines against WT CCHFV challenge in two different lethal challenge model.",,2026,Thomas Jefferson University,788347,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Characterisation of vaccine-induced immunity",2022 +P21796,5R01AI152241-03,Vaccines for Prevention of RG3 and RG4 Emerging Tickborne Viral Diseases,"PROJECT SUMMARY Tickborne illnesses continue to be a significant public health concern in the US and worldwide, as environmental and climate changes have allowed the dramatic expansion of ticks, tick habitats, and their mammalian hosts. In the New England region alone, Lone Star ticks were first reported in 2017, followed by the establishment of exotic Asian longhorned ticks in 2018. A recent CDC report indicates that tickborne diseases in the US have more than doubled from 2004 to 2016, accounting for 77% of all reported vector-borne diseases. The report also indicates that the US is not fully prepared to prevent and control these threats. A number of tickborne viruses that cause encephalitis and hemorrhagic fever in humans are of particular concern in the US, such as the re-emerging Powassan virus (POWV), as well as the recently discovered Heartland virus (HRTV). Another emerging tickborne virus in Asia is severe fever with thrombocytopenia syndrome virus (SFTSV), closely related to HRTV, which is transmitted by the Asian longhorned tick that is spreading rapidly and is now present in 12 US states. A number of additional exotic tickborne viral agents are of concern to the US, including tickborne encephalitis virus (TBEV), Omsk hemorrhagic fever virus (OHFV), and Crimean-Congo hemorrhagic fever virus (CCHFV). To better prepare for these emerging threats, we assembled a team of experts in (1) vaccine development at the University of Connecticut, (2) tickborne viruses at the Connecticut Agricultural Experiment Station, and (3) animal models in maximum biocontainment at the National Emerging Infectious Diseases Laboratories and propose the development and testing of vaccines for four Risk Group 3 (RG3) and RG4 tickborne encephalitis and hemorrhagic fever viruses classified as NIAID Category A or C Priority Pathogens, and prioritized by the WHO under its most recent 2018 Blueprint list of priority diseases in need of accelerated research and development. We developed a rapid method to generate vaccinia virus (VACV) vectors that will allow us to quickly test a number of tickborne viral genes to ensure robust expression of protective antigens and secretion of virus-like particles (VLPs). This platform is based on a gold-standard viral vector (VACV) that induces high levels of humoral and cell-mediated immune responses. These VACV vectors are replication-defective when administered as a vaccine, yet easy to propagate in standard cell culture at high titers, unlike other replication-defective poxvirus vectors such as MVA. We will also generate DNA- based vaccines and purified VLPs (as a subunit vaccine), so that three different classes of vaccine candidates can be tested for immunogenicity, either alone or in prime-boost regimens. Finally, we will test the efficacy of the vaccines using tick-transmission animal models to recapitulate the enhancement of transmission and dissemination that has been documented by tick feeding.",,2026,University Of Connecticut Storrs,499355,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Novel Pathogen | Unspecified,,,,,,,,,Crimean-Congo haemorrhagic fever | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P21797,5U01AI151698-04,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,1609959,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21798,3U01AI151698-04S1,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,127489,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2020 +P21799,3U01AI151698-03S3,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,44501,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21803,5R01TW012434-02,Measuring human behavior and ecological dimensions of pathogen transmission for outbreak control and prevention,"This project proposes interdisciplinary research across biology and geography to examine links between human-environment interactions, spatiotemporal patterns of human mobility and health geographies, and endemic and emerging infectious diseases. This work focuses on measles and Ebola prevention and management in the Équateur province in the Democratic Republic of Congo (DRC), where both pathogens cause significant morbidity and mortality. Recurring outbreaks emphasize an urgent need for significant public health improvements. This research investigates the mechanisms underlying pathogen transmission and identifies epidemiological units, across which transmission occurs, and measure their vulnerability to outbreaks. Outputs will be developed with and for mobile health teams in the DRC and will provide a generalizable blueprint for the broader application of this approach across a range of contexts. The proposed research targets the intersection of theoretical frameworks to examine four interlinked topics. First, following Cutter in 2003, this project will develop formal spatial methods to identify and delineate epidemiological units of pathogen transmission and measure their epidemiological vulnerability. Vulnerability is determined by the mechanisms underlying locally specific transmission processes, which differ across diseases. This work includes health data quality as a problem that allow public health problems to persist where they most need improvement. Second, building on Kwan’s 2013 work, this research will start with R1’s epidemiological units and vulnerability indices and integrate the dynamics of seasonal and long-term population mobility, connectivity, and distribution. Population dynamics drive contacts, transmission, and spread for communicable pathogens and must be included in vaccinations and outbreak response. Third, extending Shuurman’s 2011 work, this research will visually represent these dynamic epidemiological units and vulnerability indices cartographically to advance methods in geovisualizations and provide usable spatial decision support systems (SDSS) for mobile health efforts. To maximize clarity and usability, these visualizations will be rigorously developed and tested with our collaborating humanitarian organization’s field teams and graduate students in infectious diseases and geography. Fourth, this work will develop dynamic quantitative models to produce formal comparisons of intervention strategies and iteratively improve them. Models will compare A) strategies using the proposed SDSS, which highlight acting on the vulnerability of epidemiological units of transmission before outbreaks occur for immunizations and outbreak responses and B) the current system, which is guided by administrative boundaries and case rate thresholds to trigger response. Linking spatial and temporal elements of human-environment interactions to support infectious disease prevention and outbreak management will significantly advance the current methods and theory in this field.",,2027,"Pennsylvania State University, The",464044,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease surveillance & mapping | Approaches to public health interventions,2022 +P21806,5R01EY031894-03,NeuroEbola,"SUMMARY Ebolaviruses (EBOV) are among the deadliest pathogens known to man, with a case fatality rate of 25â€Â""90% depending on the outbreak. For the first time, monoclonal antibodies Zmapp, Mab114, REGN-EB3 and Remdesivir (inhibitor of viral RNA synthesis) were used, improving survival rates in Ebola treatment units (ETU) during the ongoing outbreak of Ebola virus disease (EVD) in Congo-Kinshasa. Despite treatments, 34% of EVD survivors experienced eye complications. In addition, they had lower [mean (SD)] minimental test examination (MMSE) scores i.e. [25 (5.5)] relative to controls [29.9 (0.6)] (p < 0.01); and women perform poorly [24.8 (5.90] relative to men [28.4 (3.2)](p < 0.01). The odds of depression were higher in EVD survivors [OR: 14.9 (95%CI: 4.4 â€Â"" 50.1)], mostly in women [OR: 4.4. (95%CI: 2.1 â€Â"" 9.6)] and, intriguingly, MMSE deficit in women was associated with higher initial EBOV viral load [OR: 0.84 (95%CI: 0.73 â€Â"" 0.98, p = 0.03, for one-unit increase in ctXptNP; lower ctXpt = higher viral load] after adjustment for age and depression status. EBOV persisted in breastmilk, wet preps, and semen for several months after acute EVD. We propose to test the hypothesis that occurrence of neuroophthalmologic sequalae is dictated by initial and/or persistence of EBOV viral load with discernable IgG responses, and/or a persistent inflammatory state driven by elevated cytokines and immune cell activation; by addressing the following specific aims: Aim 1. To contrast neuro- ophthalmologic deficits (spectrum & extent) found in confirmed EVD survivors to relevant profiles seen in their IgG+ but EVD-free close contacts, and IgG- controls (N = 90 per group). In Aim 1A, study participants will have longitudinal (0, 6, 12, 24, 36, and 48 month-time-points) assessments of neurocognition using the computerized Test of Variables of Attention (auditory and visual), the Test of Attentional Performance, and CogState for nonverbal cognitive skills. In Aim 1B, they will undergo psychophysical tests for visual acuity, contrast sensitivity, color vision, and visual field; as well as spectral domain-optical coherence tomography to elucidate structural biomarkers of disease within visual pathways. Aim differences levels overabundance 2 will determine whether group- on neuroophthalmologic outcomes found in Aim 1 are mediated by EBOV viral load or persistence, of anti-EBOV IgG, alterations in levels or activation status of circulating immune cells, and/or of proinflammatory cytokines. Aim 3 will enhance capacity in neurocognitive assessments, ophthalmologic evaluations and EVD immunoprofiling and molecular biology (RT-PCR). Gaps of knowledge to be filled include lack of understanding of (1) EBOV persistence, (2) long-lasting immune dysregulation, (3) IgG positivity with no overt EVD symptoms, all in contexts of post-EVD treatment. The overall goal of the proposed work aligns with the global health mission of the NIH while integrating the institute-specific missions of FIC, NEI, NIAID, NINDS, and the Office of Disease Prevention.",,2026,Oregon Health & Science University,529057,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P21809,5R01AI148127-04,Emerging methods and applications for test-negative studies of of infectious disease interventions,"PROJECT SUMMARY/ABSTRACT The need for longitudinal follow-up of individuals exposed to interventions against rare infectious disease endpoints poses a barrier to prospective efficacy and effectiveness studies. Studies using the test-negative design (TND) have become a popular alternative. TNDs represent a variant on traditional case-control designs: studies enroll subjects who seek care for a clinical syndrome, defining those who test positive and negative for a pathogen of interest as “cases” and “controls”, respectively. To facilitate rigorous and reproducible assessments of vaccine performance, the project will re-assess emerging applications of the TND, and contribute methods to measure intervention effects from data collected by TND studies. The first two aims revisit estimation strategies for vaccine-conferred protection against infection and against the progression of infection to diseaseâ€Â""the two components of the vaccine “direct effect” that TND studies aim to measure. We propose novel frameworks to estimate each effect through extensions of the TND: one through comparisons of symptomatic and asymptomatic persons, and another leveraging the age distribution of cases. We will apply these methods to estimate pneumococcal conjugate vaccine effectiveness against vaccine-serotype pneumococcal pneumonia and carriage, and to re-assess reported differences in rotavirus vaccine effectiveness across high, middle, and low-income countries. In Aim 3, we will continue development of statistical procedures for cluster randomized test- negative designs. A major field trial of this nature for a vector intervention utilizing the bacterium Wolbachia to reduce dengue fever transmission is nearing completion. Permutation- based inference is planned because of small numbers of clusters. We will extend such methods (i) to allow for individual measures of intervention exposure (based on human and mosquito mobility), and (ii) to include design variants such as the stepped wedge design and interrupted time series where data collection has either recently ended or is in process. We will also consider a novel application to assess a new vaccine against Ebola Virus Disease (EVD) in the Democratic Republic of the Congo. This project will thus contribute methods and computational routines to allow valid inferences from TND study data, permitting novel assessments of interventions against rotavirus, pneumococcal disease, EVD, and dengue etc.",,2024,University Of California Berkeley,437670,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2020 +P21815,5R01AI153524-04,Immunological characterization of rationally-designed vaccines against plague in mice and non-human primate models,"ABSTRACT The increasing number of bubonic/pneumonic plague cases globally (2010-2018), including the U.S., with a ~18% case fatality rate may reflect climate changes and a rodent carrier range shift. The 2017-18 plague outbreak in Madagascar with ~2400 cases (>75% pneumonic) and ~9% causalities has led WHO (April 2018) to intensify the need for developing new generation subunit and live-attenuated plague vaccines. This need is exemplified by deadly plague cases in China (2019) and Congo (2020 with a 35% fatality rate). Y. pestis’ (Yp) ability to persist in dead hosts to resurge after years of silence, existence of antibiotic-resistant strains that occur naturally or have been intentionally developed, and no FDA-approved plague vaccine, is fearsome. Two- component subunit vaccines composed of capsular antigen F1 and a T3SS component and effector LcrV (low calcium response V antigen), which only generate a humoral immune response, provide variable protection in African green monkeys (AGM) and generate poor T cell responses in humans. Such vaccines will not be effective against Yp strains lacking F1 or possessing LcrV variants. Since the cellular immunity is also critical for protection, we focused first on identifying new virulence genes of Yp and then to delete them in combination to develop novel live-attenuated vaccine (LAV) strains. Two such LAVs were 100% attenuated in inducing bubonic/pneumonic plague in mice/rats and generated long-term humoral and cellular immune responses to provide 100% protection to rodents against developing plague. No clinical symptoms of the disease or histopathological lesions were noted either during immunization or when the vaccinated animals were subsequently exposed to Yp CO92 in a more stringent pneumonic plague model. Therefore, further immunological characterization of these mutants and their testing in higher animals, such as cynomolgus macaques (CM) and AGM, will provide a rationale for future clinical studies. There is a precedent for using a LAV against plague (EV76 strain) in humans. However, this vaccine is reactogenic, represents a spontaneous mutant, and causes disease in patients with over iron load. In Aim 1, we will demonstrate efficacy and immune responses of two vaccine candidates generated from Yp CO92 (biovar Orientalis) against other Yp biovars (Antiqua and Medievalis), the F1-minus mutant of CO92, and Yp CO92 with LcrV variants, in bubonic and pneumonic mouse models. Our data with the mutants indicated a role of IL-17 (a Th17 cytokine), Th1-IFN-γ, and antibodies, in protection. In Aim 2, we will study the mechanistic basis of this protection (one chosen mutant) by using RORt-/- mice, which lack Th17 cells, as well as IFN-γ and IgA k/o mice, to discern their links to neutrophil recruitment and mucosal immunity, to combat Yp infection in bubonic/pneumonic plague models. In Aim 3, CM and AGM will be used with one mutant to demonstrate its short- and long-term efficacy in causing bubonic and/or pneumonic plague as well as reactogenicity. The correlates of protective immunity will then be established. These innovative mechanistic/translational approaches will result in effective new generation plague vaccines.",,2026,University Of Texas Med Br Galveston,155496,Animals | Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies | Vaccine design and administration",2021 +P21823,5R01AI168362-02,Optimizing Ridaifen-B analogs as potential therapeutics for Ebola viruses,"Summary Ebola virus disease (EVD) is caused by an infection with a group of viruses within the genus Ebolavirus. There are at least five species of Ebolavirus, Ebola virus (Zaire, EBOV), Ebola Sudan (SUDV), Bundibugyo virus (BDBV), Reston virus and Tai Forest virus (TAFV). Infections with these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates, and are associated with up to 90% mortality rates with EBOV. Because of the safety concerns, these viruses are designated as the biosafety level 4 agents. Currently there is no effective therapeutic treatments against Ebola virus infection and pathogenesis in humans. Thus the goal of this application is to develop GP-specific small molecule inhibitors as drugs which can be used prophylactically and therapeutically against EBOV and other Ebola virus infections. To achieve this, we screened an in-house library of small molecules, and identified numerous potent entry inhibitors against EBOV. We have identified a series of potent compounds and will use them as leads which will be chemically optimized and developed as an anti-Ebola virus therapy candidate. In this application, two specific aims are proposed: (1) structure- based optimization of the lead compounds, and (2) In vivo evaluation of the lead compounds against EBOV infection using animal models.",,2027,University Of Illinois At Chicago,780190,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P21825,5U01AI151799-04,Emerging Infectious Diseases Research Center - East and Central Africa,"PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.",,2025,Washington State University,1209678,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping",2020 +P21826,6U01GH002319-03M002,"GH21-004, COVID-19 and related public health threats in populations affected by crises: a multi-disciplinary, collaborative research programme","Project summary / abstract In response to the Centers for Disease Control and Prevention’s Notice of Funding Opportunity to conduct research among crisis-affected and displaced populations in the context of COVID-19, we hereby propose a five- year programme of research and capacity strengthening , focussed on four key crisis-affected countries (the Democratic Republic of Congo, Somalia, South Sudan and Sudan), but with flexibility to conduct data collection in new emergencies and other settings where existing collaborations facilitate this. We present below a set of activities and studies organised along three aims: Aim 1: Establish or strengthen country-based, locally-led, multi-disciplinary humanitarian public health research units in the four key countries. Aim 2: Explore novel cross-cutting methods based on community-led surveillance and data science methods . Aim 3: Generate thematic evidence on the direct and indirect impacts of COVID-19 and other emergent public health threats, as per the following scientific objectives: 1. Generate improved all-cause and cause-specific 2. Quantify of SARS-CoV-2 and other epidemic infections. 3. Explore changes to behaviours, improve monitoring of hygiene behaviours and evaluate mortality estimates. transmission hygiene alternative behaviour change interventions. 4. Quantify and describe COVID-19’s secondary impacts on 5. Quantify COVID-19’s impacts on care models. sexual and reproductive health . non-communicable disease burden and mental health and test novel These activities will be undertaken by a consortium of academic institutions (the London School of Hygiene and Tropical Medicine, London, UK; the Université Catholique de Bukavu, DRC; SIMAD University, Mogadishu, Somalia; Imperial College London) and (the Bridge Network Organisation, South Sudan; the Sudan Youth Peer Network and Adeela for Art and Culture, Sudan). Our partnership is committed to co- production principles and will adopt a decolonial approach to research and humanitarian action. Most team members are former humanitarian workers, and all conduct the majority or all of their research work in or on crisis-affected populations. civil society actors",,2026,London School of Hygiene & Tropical Medicine,487709,Human Populations | Other,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,,Data Management and Data Sharing,,,United Kingdom,,"Epidemiological studies | Infection prevention and control | Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts | Systemic/environmental components of capacity strengthening,2022 +P21827,5U01GH002319-03,"RFA-GH-21-004, COVID-19 and related public health threats in populations affected by crises: a multi-disciplinary, collaborative research programme","Project summary / abstract In response to the Centers for Disease Control and Prevention’s Notice of Funding Opportunity to conduct research among crisis-affected and displaced populations in the context of COVID-19, we hereby propose a five- year programme of research and capacity strengthening , focussed on four key crisis-affected countries (the Democratic Republic of Congo, Somalia, South Sudan and Sudan), but with flexibility to conduct data collection in new emergencies and other settings where existing collaborations facilitate this. We present below a set of activities and studies organised along three aims: Aim 1: Establish or strengthen country-based, locally-led, multi-disciplinary humanitarian public health research units in the four key countries. Aim 2: Explore novel cross-cutting methods based on community-led surveillance and data science methods . Aim 3: Generate thematic evidence on the direct and indirect impacts of COVID-19 and other emergent public health threats, as per the following scientific objectives: 1. Generate improved all-cause and cause-specific 2. Quantify of SARS-CoV-2 and other epidemic infections. 3. Explore changes to behaviours, improve monitoring of hygiene behaviours and evaluate mortality estimates. transmission hygiene alternative behaviour change interventions. 4. Quantify and describe COVID-19's secondary impacts on 5. Quantify COVID-19's impacts on care models. sexual and reproductive health . non-communicable disease burden and mental health and test novel These activities will be undertaken by a consortium of academic institutions (the London School of Hygiene and Tropical Medicine, London, UK; the Université Catholique de Bukavu, DRC; SIMAD University, Mogadishu, Somalia; Imperial College London) and (the Bridge Network Organisation, South Sudan; the Sudan Youth Peer Network and Adeela for Art and Culture, Sudan). Our partnership is committed to co- production principles and will adopt a decolonial approach to research and humanitarian action. Most team members are former humanitarian workers, and all conduct the majority or all of their research work in or on crisis-affected populations. civil society actors",,2026,London School of Hygiene & Tropical Medicine,112291,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Epidemiological studies",Community engagement | Indirect health impacts | Disease surveillance & mapping,2022 +P21828,5U01GH002338-03,"RFA-GH-21-006, SICA Study: Seroepidemiological Insight into COVID-19 transmission in Africa","PROJECT SUMMARY The COVID-19 pandemic has resulted in vastly different health outcomes for populations in Sub-Saharan Africa as compared to other countries with comparatively higher case numbers and deaths. The comparatively low numbers of cases and deaths reported in the Democratic Republic of Congo (DRC) and Nigeria, as well as throughout sub-Saharan Africa, are likely reflective of poor healthcare infrastructure and limited testing capacity. It is also unclear how the level of transmission of SARS-CoV-2 in urban vs. rural settings may influence COVID- 19 severity and the subsequent identification of cases by testing sites in both countries. Our overarching hypothesis is that prior exposure to related coronaviruses and other pathogens, which partition differentially in urban vs. rural communities, have resulted in significant cross-protective immunity or innate immune priming in the population, which leads to a reduced COVID-19 burden in these countries. We will leverage ongoing longitudinal cohort studies in urban and rural sites in the DRC and Nigeria, to support the characterization of: (i) the incidence of and risk factors for SARS-CoV-2 infection and COVID-19 severity, (ii) the current distribution and severity of respiratory/non-respiratory viral and non-viral pathogens as a cause of non-COVID-19 acute febrile illness, and (iii) role that exposure to syndemic pathogens have on COVID-19 severity. To this end, we propose to describe the incidence and prevalence of SARS-CoV-2 using seroepidemiology and describe factors associated with incidence and recovery (AIM1) and the epidemiology of respiratory and non-respiratory viral or parasitic pathogens viz. acute febrile illness (AFI) during the COVID-19 pandemic (AIM2). Our long-standing relationships through community engagement activities, and direct ties to the Public Health ministries as well as the Africa Centres for Disease Control allow us to obtain and convey accurate data at local resolution. We envision that this multinational surveillance project will provide much needed insight into the epidemiology of SARS-CoV-2 infection and COVID-19 disease in the DRC and Nigeria, elucidating differences in the incidence and disease outcomes across a range of urban vs. rural settings, which in turn can inform public health policy and control measures at country and regional levels.",,2026,University Of Florida,1,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2021 +P21832,1R43AI174350-01A1,Preclinical development of a Nipah Virus inhibitor,"Project Summary SARS-CoV-2 has led to an increased urgency to develop treatments for additional emerging viruses and potentially provide broader spectrum antivirals in order to anticipate pandemic viruses. Nipah virus (NiV) is a bat-borne pathogen (family Paramyxoviridae) that results in acute and often fatal (recent outbreaks in India have demonstrated case fatality ~70%) respiratory and neurological disease for which there is currently no FDA approved treatment. There have been very few small molecule antivirals that have demonstrated activity against NiV either in vitro or in vivo. These include favipiravir (EC90 15.87- 123.8 Ã'µM) which resulted in survival in the hamster model and remdesivir (EC90 50-100 nM) when dosed daily by the intravenous (IV) route in the African green monkey (AGM) model resulting in their survival. We recently identified the antiviral activity of pyronaridine (EC50 = 65.57 nM and CC50 3.65 Ã'µM) for NiV (Malaysia strain, Patent No. 17/092,058). We have also shown that pyronaridine has efficacy against Ebola in vitro and efficacy in vivo in mice and guinea pig. Additionally, pyronaridine has demonstrated promising activity in vitro against Marburg virus and in vivo efficacy against SARS-CoV-2 in mice. We have recently shown that pyronaridine is lysosomotropic and binds to the Ebola glycoprotein as well as decreases the inflammatory cytokine storm in mice induced by SARS-CoV-2. We now propose to assess the oral maximum tolerated dose and pharmacokinetics prior to performing efficacy studies in the hamster model of NiV. If we are successful in demonstrating in vivo efficacy, we will file an orphan drug designation and a preIND with the FDA. If we demonstrate statistically significant efficacy in Phase I we will then perform efficacy testing in Phase II using the African Green Monkey model for NiV, perform IND enabling toxicology studies and manufacture GMP grade pyronaridine tertraphosphate. Our ultimate aim is to bring a treatment to market for NiV which can be stockpiled by the USA and other countries in preparation for future outbreaks.",,2024,"COLLABORATIONS PHARMACEUTICALS, INC.",295096,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Phase 0 clinical trial | Phase 1 clinical trial | Phase 2 clinical trial,2023 +P21841,1R01AI167295-01A1,Analysis of a novel Crimean-Congo hemorrhagic fever vaccine and its mechanism of protection in rodent models,"Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease in humans, with fatality rates reaching 40%. CCHFV is endemic to parts of Africa, Asia, the Middle East, and Europe, specifically to regions where the tick vector, species of the Hyalomma genus, is present. Classified as an NIH/NIAID Category A and WHO high- priority pathogen, CCHFV poses the highest possible risk to national security and public health. CCHFV is a negative-sense single-stranded RNA virus in the order Bunyavirales. CCHFV is an Emerging Infectious Disease, posing a high risk of a widespread outbreak. An inactivated whole virus vaccine was the only CCHFV vaccine to be tested in humans and was ineffective. We propose the use of inactivated rabies virus (RABV)- and vesicular stomatitis virus (VSV)-based CCHFV vaccines, as inactivated rhabdoviral vectors have not yet been explored. Inactivated rhabdoviral-based vaccines are safe and effective at inducing immunity and protection against multiple hemorrhagic fever viruses, and a VSV-based surrogate challenge virus is an effective tool in another hemorrhagic fever model. The goal of this project is two-fold: first, to compare RABV- and VSV-based CCHFV/RABV bivalent vaccines in terms of their production, immunogenicity; second, to establish a non-BSL-4 VSV-based surrogate mouse challenge system for CCHFV to determine mechanism of protection. We hypothesize that inactivated rhabdoviral-based CCHFV vaccines will protect against the CCHFV challenge through non-neutralizing antibodies directed against GP38. Toward this hypothesis, we propose three Aims: Aim 1: Characterization of Rhabdoviral-based CCHFV vaccine constructs. This aim does characterize and test the immunogenicity of RABV- and VSV-based CCHFV vaccines and compare them to the Bulgaria human vaccine and an mRNA-based vaccine provided by collaborators. Aim 2: Determine rhabdoviral-based CCHFV vaccine mechanism of protection by establishing a surrogate challenge virus model. This aim aims to develop a non-BSL-4-requiring surrogate challenge model for CCHFV and compare it to the established BSL-4 WT CCHFV model in vaccine efficacy studies. Aim 3: Evaluate the protective efficacy of rhabdoviral-based vaccine candidates in a wildtype CCHFV lethal challenge model using needle and tick challenge. The goal of this aim is to determine the efficacy of our rhabdoviral-based vaccines and control vaccines against WT CCHFV challenge in two different lethal challenge model.",,2026,Thomas Jefferson University,779687,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Characterisation of vaccine-induced immunity",2022 +P21842,5R01AI152241-02,Vaccines for Prevention of RG3 and RG4 Emerging Tickborne Viral Diseases,"PROJECT SUMMARY Tickborne illnesses continue to be a significant public health concern in the US and worldwide, as environmental and climate changes have allowed the dramatic expansion of ticks, tick habitats, and their mammalian hosts. In the New England region alone, Lone Star ticks were first reported in 2017, followed by the establishment of exotic Asian longhorned ticks in 2018. A recent CDC report indicates that tickborne diseases in the US have more than doubled from 2004 to 2016, accounting for 77% of all reported vector-borne diseases. The report also indicates that the US is not fully prepared to prevent and control these threats. A number of tickborne viruses that cause encephalitis and hemorrhagic fever in humans are of particular concern in the US, such as the re-emerging Powassan virus (POWV), as well as the recently discovered Heartland virus (HRTV). Another emerging tickborne virus in Asia is severe fever with thrombocytopenia syndrome virus (SFTSV), closely related to HRTV, which is transmitted by the Asian longhorned tick that is spreading rapidly and is now present in 12 US states. A number of additional exotic tickborne viral agents are of concern to the US, including tickborne encephalitis virus (TBEV), Omsk hemorrhagic fever virus (OHFV), and Crimean-Congo hemorrhagic fever virus (CCHFV). To better prepare for these emerging threats, we assembled a team of experts in (1) vaccine development at the University of Connecticut, (2) tickborne viruses at the Connecticut Agricultural Experiment Station, and (3) animal models in maximum biocontainment at the National Emerging Infectious Diseases Laboratories and propose the development and testing of vaccines for four Risk Group 3 (RG3) and RG4 tickborne encephalitis and hemorrhagic fever viruses classified as NIAID Category A or C Priority Pathogens, and prioritized by the WHO under its most recent 2018 Blueprint list of priority diseases in need of accelerated research and development. We developed a rapid method to generate vaccinia virus (VACV) vectors that will allow us to quickly test a number of tickborne viral genes to ensure robust expression of protective antigens and secretion of virus-like particles (VLPs). This platform is based on a gold-standard viral vector (VACV) that induces high levels of humoral and cell-mediated immune responses. These VACV vectors are replication-defective when administered as a vaccine, yet easy to propagate in standard cell culture at high titers, unlike other replication-defective poxvirus vectors such as MVA. We will also generate DNA- based vaccines and purified VLPs (as a subunit vaccine), so that three different classes of vaccine candidates can be tested for immunogenicity, either alone or in prime-boost regimens. Finally, we will test the efficacy of the vaccines using tick-transmission animal models to recapitulate the enhancement of transmission and dissemination that has been documented by tick feeding.",,2026,University Of Connecticut Storrs,499355,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Unspecified,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Disease models | Pre-clinical studies",2021 +P21844,3U01AI151758-03S1,"Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa","PROJECT SUMMARY Background: In Cambodia, ticks and tick-borne diseases are neglected and data are still lacking. Objectives: In the present proposal, we aim to identify tick species and associated pathogens including virus and bacteria circulating in rural Cambodia. Additionally, we plan to investigate transmission risk of a number of selected tick- borne pathogens known to circulate in the region in human by assessing seroprevalence (IgG) and tick bite biomarkers in people living in the communities where ticks are captured. Methods: Our study will be nestled in a study, namely “Study of dengue-like illness in Kampong Thom Province, Cambodia” (DENTHOM) which is part of a NIH/NIAID-funded project, namely “Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa” (U01 AI151758-01). Tick collections will be planned according to the parent study (DENTHOM). In terms of human samples, the present study involves only biospecimen collected in the framework of the DENTHOM study. No collection of human biological specimens will be specifically performed for the present proposal. The collected tick specimens will be first identified morphologically and confirmed using Maldi-TOF MS. Once identified, the specimen will be killed and kept at -80Ã'°C. Ticks samples will be tested for known viruses and bacteria using molecular assays and for novel pathogens using metagenomics sequencing. Human samples will be used for seroprevalence study of commonly known tick-borne viruses and bacteria circulating in Asia and for tick bite biomarkers. Expected outcomes: Our study will provide current state of knowledge of ticks and potential risks of tick-associated pathogens circulating in Cambodia. The findings of our study would be useful for assessment of host/vector interaction and instruct diagnosis of tick-borne pathogens.",,2025,INSTITUT PASTEUR,147388,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Vector biology,2020 +P21847,3U01AI151698-03S1,University of Washington Arboviral Research Network (UWARN),"Abstract: University of Washington Arboviral Research Network (UWARN) The University of Washington Arboviral Research Network (UWARN) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Metacenter for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2023,University Of Washington,664481,Animals | Human Populations | Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2021 +P21848,3U01AI151698-03S2,University of Washington Arboviral Research Network (UWARN),"Abstract: University of Washington Arboviral Research Network (UWARN) The University of Washington Arboviral Research Network (UWARN) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Metacenter for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2023,University Of Washington,1166044,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2022 +P21849,5U01AI151698-03,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,1691975,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21850,5R21AI156406-02,Infection and prevalence of a new segmented flavivirus in the United States,"Summary/abstract Segmented RNA viruses that share phylogenetic relatedness with the prototypic Flaviviruses in their helicase (NS3) and polymerase (NS5) proteins were recently identified from ticks, mosquitoes, and vertebrates, including humans suffering with febrile illness. The first Flavi-like segmented viruses (FLSV) were isolated from ticks and animals in the Jingmen province of China and were thus named Jingmen Tick Virus. Subsequently, highly diverse FLSV variants were found in Africa, Europe and South America. However, no evidence of FLSV infection has been reported in North America, including the United States. Moreover, several recent studies that used metagenomics-based identification of the virome in ticks failed to identify FLSV infection. We were characterizing the virome of free-ranging mice of the genus Peromyscus, the most common wild mouse species of the North America, when we identified a highly diverse FLSV in several deer mice from woodlands in Pennsylvania (FLSV- PN). We acquired partial sequences of all five segments of the FLSV-PN genome and developed serological assays using Luciferase immunoprecipitation systems. Our serological data suggest that FLSV-PN or its related variants have a wide host range and infect several economically important farm and domestic animals. Most importantly, we found strong evidence of FLSV-PN infection in humans with a history of tick-bites and Lyme disease. The long-term goal of our exploratory/developmental proposal is to define the pathogenesis and health relevance of FLSV-PN infection. Development of molecular reagents for this new virus will allow us to test our hypotheses that several genetically diverse FLSV variants are circulating in the United States, and these viruses are predominantly transmitted by ticks to humans and animals. Specific aim-1 is to acquire the complete genomes of several diverse FLSV variants. Our preliminary data suggest that FLSV-PN genome is comprised of five RNA segments that are polyadenylated at the 3’ end. Complete genome sequencing of FLSV-PN is necessary for the development of sensitive and specific diagnostic assays to study infection prevalence and disease associations. Specific aim-2 is to determine the infection prevalence of FLSV in humans, domesticated animals and ticks. These studies will be aided by samples and data available from clinical research studies of Lyme disease at NIAID, NIH (letter of support attached). The proposed aims represent crucial steps toward detailed molecular and biological characterization of FLSV-PN, including the development of a reverse genetics system, replicon systems, cell culture and animal models. Although the health relevance of FLSV infections is currently not known, the proposed studies will inform this knowledge as well as develop the reagents for preventing the spread of this new virus and associated diseases, if necessary.",,2023,RESEARCH INST NATIONWIDE CHILDREN'S HOSP,193513,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2021 +P21851,1R01TW012434-01,Measuring human behavior and ecological dimensions of pathogen transmission for outbreak control and prevention,"This project proposes interdisciplinary research across biology and geography to examine links between human-environment interactions, spatiotemporal patterns of human mobility and health geographies, and endemic and emerging infectious diseases. This work focuses on measles and Ebola prevention and management in the Équateur province in the Democratic Republic of Congo (DRC), where both pathogens cause significant morbidity and mortality. Recurring outbreaks emphasize an urgent need for significant public health improvements. This research investigates the mechanisms underlying pathogen transmission and identifies epidemiological units, across which transmission occurs, and measure their vulnerability to outbreaks. Outputs will be developed with and for mobile health teams in the DRC and will provide a generalizable blueprint for the broader application of this approach across a range of contexts. The proposed research targets the intersection of theoretical frameworks to examine four interlinked topics. First, following Cutter in 2003, this project will develop formal spatial methods to identify and delineate epidemiological units of pathogen transmission and measure their epidemiological vulnerability. Vulnerability is determined by the mechanisms underlying locally specific transmission processes, which differ across diseases. This work includes health data quality as a problem that allow public health problems to persist where they most need improvement. Second, building on Kwan’s 2013 work, this research will start with R1’s epidemiological units and vulnerability indices and integrate the dynamics of seasonal and long-term population mobility, connectivity, and distribution. Population dynamics drive contacts, transmission, and spread for communicable pathogens and must be included in vaccinations and outbreak response. Third, extending Shuurman’s 2011 work, this research will visually represent these dynamic epidemiological units and vulnerability indices cartographically to advance methods in geovisualizations and provide usable spatial decision support systems (SDSS) for mobile health efforts. To maximize clarity and usability, these visualizations will be rigorously developed and tested with our collaborating humanitarian organization’s field teams and graduate students in infectious diseases and geography. Fourth, this work will develop dynamic quantitative models to produce formal comparisons of intervention strategies and iteratively improve them. Models will compare A) strategies using the proposed SDSS, which highlight acting on the vulnerability of epidemiological units of transmission before outbreaks occur for immunizations and outbreak responses and B) the current system, which is guided by administrative boundaries and case rate thresholds to trigger response. Linking spatial and temporal elements of human-environment interactions to support infectious disease prevention and outbreak management will significantly advance the current methods and theory in this field.",,2027,"Pennsylvania State University, The",442596,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease surveillance & mapping | Approaches to public health interventions,2022 +P21854,5R01EY031894-02,NeuroEbola,"SUMMARY Ebolaviruses (EBOV) are among the deadliest pathogens known to man, with a case fatality rate of 25â€Â""90% depending on the outbreak. For the first time, monoclonal antibodies Zmapp, Mab114, REGN-EB3 and Remdesivir (inhibitor of viral RNA synthesis) were used, improving survival rates in Ebola treatment units (ETU) during the ongoing outbreak of Ebola virus disease (EVD) in Congo-Kinshasa. Despite treatments, 34% of EVD survivors experienced eye complications. In addition, they had lower [mean (SD)] minimental test examination (MMSE) scores i.e. [25 (5.5)] relative to controls [29.9 (0.6)] (p < 0.01); and women perform poorly [24.8 (5.90] relative to men [28.4 (3.2)](p < 0.01). The odds of depression were higher in EVD survivors [OR: 14.9 (95%CI: 4.4 â€Â"" 50.1)], mostly in women [OR: 4.4. (95%CI: 2.1 â€Â"" 9.6)] and, intriguingly, MMSE deficit in women was associated with higher initial EBOV viral load [OR: 0.84 (95%CI: 0.73 â€Â"" 0.98, p = 0.03, for one-unit increase in ctXptNP; lower ctXpt = higher viral load] after adjustment for age and depression status. EBOV persisted in breastmilk, wet preps, and semen for several months after acute EVD. We propose to test the hypothesis that occurrence of neuroophthalmologic sequalae is dictated by initial and/or persistence of EBOV viral load with discernable IgG responses, and/or a persistent inflammatory state driven by elevated cytokines and immune cell activation; by addressing the following specific aims: Aim 1. To contrast neuro- ophthalmologic deficits (spectrum & extent) found in confirmed EVD survivors to relevant profiles seen in their IgG+ but EVD-free close contacts, and IgG- controls (N = 90 per group). In Aim 1A, study participants will have longitudinal (0, 6, 12, 24, 36, and 48 month-time-points) assessments of neurocognition using the computerized Test of Variables of Attention (auditory and visual), the Test of Attentional Performance, and CogState for nonverbal cognitive skills. In Aim 1B, they will undergo psychophysical tests for visual acuity, contrast sensitivity, color vision, and visual field; as well as spectral domain-optical coherence tomography to elucidate structural biomarkers of disease within visual pathways. Aim differences levels overabundance 2 will determine whether group- on neuroophthalmologic outcomes found in Aim 1 are mediated by EBOV viral load or persistence, of anti-EBOV IgG, alterations in levels or activation status of circulating immune cells, and/or of proinflammatory cytokines. Aim 3 will enhance capacity in neurocognitive assessments, ophthalmologic evaluations and EVD immunoprofiling and molecular biology (RT-PCR). Gaps of knowledge to be filled include lack of understanding of (1) EBOV persistence, (2) long-lasting immune dysregulation, (3) IgG positivity with no overt EVD symptoms, all in contexts of post-EVD treatment. The overall goal of the proposed work aligns with the global health mission of the NIH while integrating the institute-specific missions of FIC, NEI, NIAID, NINDS, and the Office of Disease Prevention.",,2026,Oregon Health & Science University,533740,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P21856,5R01AI148127-03,Emerging methods and applications for test-negative studies of of infectious disease interventions,"PROJECT SUMMARY/ABSTRACT The need for longitudinal follow-up of individuals exposed to interventions against rare infectious disease endpoints poses a barrier to prospective efficacy and effectiveness studies. Studies using the test-negative design (TND) have become a popular alternative. TNDs represent a variant on traditional case-control designs: studies enroll subjects who seek care for a clinical syndrome, defining those who test positive and negative for a pathogen of interest as “cases” and “controls”, respectively. To facilitate rigorous and reproducible assessments of vaccine performance, the project will re-assess emerging applications of the TND, and contribute methods to measure intervention effects from data collected by TND studies. The first two aims revisit estimation strategies for vaccine-conferred protection against infection and against the progression of infection to diseaseâ€Â""the two components of the vaccine “direct effect” that TND studies aim to measure. We propose novel frameworks to estimate each effect through extensions of the TND: one through comparisons of symptomatic and asymptomatic persons, and another leveraging the age distribution of cases. We will apply these methods to estimate pneumococcal conjugate vaccine effectiveness against vaccine-serotype pneumococcal pneumonia and carriage, and to re-assess reported differences in rotavirus vaccine effectiveness across high, middle, and low-income countries. In Aim 3, we will continue development of statistical procedures for cluster randomized test- negative designs. A major field trial of this nature for a vector intervention utilizing the bacterium Wolbachia to reduce dengue fever transmission is nearing completion. Permutation- based inference is planned because of small numbers of clusters. We will extend such methods (i) to allow for individual measures of intervention exposure (based on human and mosquito mobility), and (ii) to include design variants such as the stepped wedge design and interrupted time series where data collection has either recently ended or is in process. We will also consider a novel application to assess a new vaccine against Ebola Virus Disease (EVD) in the Democratic Republic of the Congo. This project will thus contribute methods and computational routines to allow valid inferences from TND study data, permitting novel assessments of interventions against rotavirus, pneumococcal disease, EVD, and dengue etc.",,2024,University Of California Berkeley,437670,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2020 +P21859,5R01AI153524-03,Immunological characterization of rationally-designed vaccines against plague in mice and non-human primate models,"ABSTRACT The increasing number of bubonic/pneumonic plague cases globally (2010-2018), including the U.S., with a ~18% case fatality rate may reflect climate changes and a rodent carrier range shift. The 2017-18 plague outbreak in Madagascar with ~2400 cases (>75% pneumonic) and ~9% causalities has led WHO (April 2018) to intensify the need for developing new generation subunit and live-attenuated plague vaccines. This need is exemplified by deadly plague cases in China (2019) and Congo (2020 with a 35% fatality rate). Y. pestis’ (Yp) ability to persist in dead hosts to resurge after years of silence, existence of antibiotic-resistant strains that occur naturally or have been intentionally developed, and no FDA-approved plague vaccine, is fearsome. Two- component subunit vaccines composed of capsular antigen F1 and a T3SS component and effector LcrV (low calcium response V antigen), which only generate a humoral immune response, provide variable protection in African green monkeys (AGM) and generate poor T cell responses in humans. Such vaccines will not be effective against Yp strains lacking F1 or possessing LcrV variants. Since the cellular immunity is also critical for protection, we focused first on identifying new virulence genes of Yp and then to delete them in combination to develop novel live-attenuated vaccine (LAV) strains. Two such LAVs were 100% attenuated in inducing bubonic/pneumonic plague in mice/rats and generated long-term humoral and cellular immune responses to provide 100% protection to rodents against developing plague. No clinical symptoms of the disease or histopathological lesions were noted either during immunization or when the vaccinated animals were subsequently exposed to Yp CO92 in a more stringent pneumonic plague model. Therefore, further immunological characterization of these mutants and their testing in higher animals, such as cynomolgus macaques (CM) and AGM, will provide a rationale for future clinical studies. There is a precedent for using a LAV against plague (EV76 strain) in humans. However, this vaccine is reactogenic, represents a spontaneous mutant, and causes disease in patients with over iron load. In Aim 1, we will demonstrate efficacy and immune responses of two vaccine candidates generated from Yp CO92 (biovar Orientalis) against other Yp biovars (Antiqua and Medievalis), the F1-minus mutant of CO92, and Yp CO92 with LcrV variants, in bubonic and pneumonic mouse models. Our data with the mutants indicated a role of IL-17 (a Th17 cytokine), Th1-IFN-γ, and antibodies, in protection. In Aim 2, we will study the mechanistic basis of this protection (one chosen mutant) by using RORt-/- mice, which lack Th17 cells, as well as IFN-γ and IgA k/o mice, to discern their links to neutrophil recruitment and mucosal immunity, to combat Yp infection in bubonic/pneumonic plague models. In Aim 3, CM and AGM will be used with one mutant to demonstrate its short- and long-term efficacy in causing bubonic and/or pneumonic plague as well as reactogenicity. The correlates of protective immunity will then be established. These innovative mechanistic/translational approaches will result in effective new generation plague vaccines.",,2025,University Of Texas Med Br Galveston,695461,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity",2021 +P21864,1R01AI168362-01A1,Optimizing Ridaifen-B analogs as potential therapeutics for Ebola viruses,"Summary Ebola virus disease (EVD) is caused by an infection with a group of viruses within the genus Ebolavirus. There are at least five species of Ebolavirus, Ebola virus (Zaire, EBOV), Ebola Sudan (SUDV), Bundibugyo virus (BDBV), Reston virus and Tai Forest virus (TAFV). Infections with these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates, and are associated with up to 90% mortality rates with EBOV. Because of the safety concerns, these viruses are designated as the biosafety level 4 agents. Currently there is no effective therapeutic treatments against Ebola virus infection and pathogenesis in humans. Thus the goal of this application is to develop GP-specific small molecule inhibitors as drugs which can be used prophylactically and therapeutically against EBOV and other Ebola virus infections. To achieve this, we screened an in-house library of small molecules, and identified numerous potent entry inhibitors against EBOV. We have identified a series of potent compounds and will use them as leads which will be chemically optimized and developed as an anti-Ebola virus therapy candidate. In this application, two specific aims are proposed: (1) structure- based optimization of the lead compounds, and (2) In vivo evaluation of the lead compounds against EBOV infection using animal models.",,2027,University Of Illinois At Chicago,795165,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P21866,5U01AI151799-03,Emerging Infectious Diseases Research Center - East and Central Africa,"PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.",,2025,Washington State University,1512188,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping",2020 +P21867,5U01GH002319-02,"GH21-004, COVID-19 and related public health threats in populations affected by crises: a multi-disciplinary, collaborative research programme","Project summary / abstract In response to the Centers for Disease Control and Prevention’s Notice of Funding Opportunity to conduct research among crisis-affected and displaced populations in the context of COVID-19, we hereby propose a five- year programme of research and capacity strengthening , focussed on four key crisis-affected countries (the Democratic Republic of Congo, Somalia, South Sudan and Sudan), but with flexibility to conduct data collection in new emergencies and other settings where existing collaborations facilitate this. We present below a set of activities and studies organised along three aims: Aim 1: Establish or strengthen country-based, locally-led, multi-disciplinary humanitarian public health research units in the four key countries. Aim 2: Explore novel cross-cutting methods based on community-led surveillance and data science methods . Aim 3: Generate thematic evidence on the direct and indirect impacts of COVID-19 and other emergent public health threats, as per the following scientific objectives: 1. Generate improved all-cause and cause-specific 2. Quantify of SARS-CoV-2 and other epidemic infections. 3. Explore changes to behaviours, improve monitoring of hygiene behaviours and evaluate mortality estimates. transmission hygiene alternative behaviour change interventions. 4. Quantify and describe COVID-19’s secondary impacts on 5. Quantify COVID-19’s impacts on care models. sexual and reproductive health . non-communicable disease burden and mental health and test novel These activities will be undertaken by a consortium of academic institutions (the London School of Hygiene and Tropical Medicine, London, UK; the Université Catholique de Bukavu, DRC; SIMAD University, Mogadishu, Somalia; Imperial College London) and (the Bridge Network Organisation, South Sudan; the Sudan Youth Peer Network and Adeela for Art and Culture, Sudan). Our partnership is committed to co- production principles and will adopt a decolonial approach to research and humanitarian action. Most team members are former humanitarian workers, and all conduct the majority or all of their research work in or on crisis-affected populations. civil society actors",,2026,London School of Hygiene & Tropical Medicine,165000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P21868,6U01GH002319-02M001,"GH21-004, COVID-19 and related public health threats in populations affected by crises: a multi-disciplinary, collaborative research programme","Project summary / abstract In response to the Centers for Disease Control and Prevention’s Notice of Funding Opportunity to conduct research among crisis-affected and displaced populations in the context of COVID-19, we hereby propose a five- year programme of research and capacity strengthening , focussed on four key crisis-affected countries (the Democratic Republic of Congo, Somalia, South Sudan and Sudan), but with flexibility to conduct data collection in new emergencies and other settings where existing collaborations facilitate this. We present below a set of activities and studies organised along three aims: Aim 1: Establish or strengthen country-based, locally-led, multi-disciplinary humanitarian public health research units in the four key countries. Aim 2: Explore novel cross-cutting methods based on community-led surveillance and data science methods . Aim 3: Generate thematic evidence on the direct and indirect impacts of COVID-19 and other emergent public health threats, as per the following scientific objectives: 1. Generate improved all-cause and cause-specific 2. Quantify of SARS-CoV-2 and other epidemic infections. 3. Explore changes to behaviours, improve monitoring of hygiene behaviours and evaluate mortality estimates. transmission hygiene alternative behaviour change interventions. 4. Quantify and describe COVID-19’s secondary impacts on 5. Quantify COVID-19’s impacts on care models. sexual and reproductive health . non-communicable disease burden and mental health and test novel These activities will be undertaken by a consortium of academic institutions (the London School of Hygiene and Tropical Medicine, London, UK; the Université Catholique de Bukavu, DRC; SIMAD University, Mogadishu, Somalia; Imperial College London) and (the Bridge Network Organisation, South Sudan; the Sudan Youth Peer Network and Adeela for Art and Culture, Sudan). Our partnership is committed to co- production principles and will adopt a decolonial approach to research and humanitarian action. Most team members are former humanitarian workers, and all conduct the majority or all of their research work in or on crisis-affected populations. civil society actors",,2026,London School of Hygiene & Tropical Medicine,607000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,United Kingdom,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Disease surveillance & mapping | Indirect health impacts,2022 +P21869,5U01GH002338-02,"RFA-GH-21-006, SICA Study: Seroepidemiological Insight into COVID-19 transmission in Africa","PROJECT SUMMARY The COVID-19 pandemic has resulted in vastly different health outcomes for populations in Sub-Saharan Africa as compared to other countries with comparatively higher case numbers and deaths. The comparatively low numbers of cases and deaths reported in the Democratic Republic of Congo (DRC) and Nigeria, as well as throughout sub-Saharan Africa, are likely reflective of poor healthcare infrastructure and limited testing capacity. It is also unclear how the level of transmission of SARS-CoV-2 in urban vs. rural settings may influence COVID- 19 severity and the subsequent identification of cases by testing sites in both countries. Our overarching hypothesis is that prior exposure to related coronaviruses and other pathogens, which partition differentially in urban vs. rural communities, have resulted in significant cross-protective immunity or innate immune priming in the population, which leads to a reduced COVID-19 burden in these countries. We will leverage ongoing longitudinal cohort studies in urban and rural sites in the DRC and Nigeria, to support the characterization of: (i) the incidence of and risk factors for SARS-CoV-2 infection and COVID-19 severity, (ii) the current distribution and severity of respiratory/non-respiratory viral and non-viral pathogens as a cause of non-COVID-19 acute febrile illness, and (iii) role that exposure to syndemic pathogens have on COVID-19 severity. To this end, we propose to describe the incidence and prevalence of SARS-CoV-2 using seroepidemiology and describe factors associated with incidence and recovery (AIM1) and the epidemiology of respiratory and non-respiratory viral or parasitic pathogens viz. acute febrile illness (AFI) during the COVID-19 pandemic (AIM2). Our long-standing relationships through community engagement activities, and direct ties to the Public Health ministries as well as the Africa Centres for Disease Control allow us to obtain and convey accurate data at local resolution. We envision that this multinational surveillance project will provide much needed insight into the epidemiology of SARS-CoV-2 infection and COVID-19 disease in the DRC and Nigeria, elucidating differences in the incidence and disease outcomes across a range of urban vs. rural settings, which in turn can inform public health policy and control measures at country and regional levels.",,2026,University Of Florida,500000,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2021 +P21876,1R15AI154949-01A1,Demonstrating the mechanism of Nairovirus translation strategy,"Abstract: Crimean Congo hemorrhagic fever is a tick born, highly contagious, viral illness with high mortality rates in humans. There is no treatment for this viral disease at present. We recently reported that Crimean Congo hemorrhagic fever virus nucleocapsid protein (CCHFV N protein) has two distinct RNA binding sites in the stalk and head domains. The RNA binding site located in the head domain non-specifically binds to the single strand RNA of viral or nonviral origin. However, the RNA binding site located in the stalk domain specifically binds to the double strand panhandle structure formed by the base pairing of highly conserved and complementary nucleotides at the 5’ and 3’ termini of the viral genome. Interestingly the viral mRNA 5’ UTR also folds into a panhandle-like secondary structure, which is also specifically recognized by the stalk domain of N protein. The interaction between N protein and viral mRNA 5’ UTR facilitates the translation of downstream open reading frame (ORF). The majority of eukaryotic mRNA translation is m7G cap dependent and is initiated by the assembly of eIF4F cap binding complex, composed of three initiation factors eIF4E, eIF4A and eIF4G. Our preliminary data shows that N protein mediated translation strategy does not require the assembly of eIF4F complex but the structural integrity of individual components of this complex is required for this viral translation mechanism. This published data suggests that CHFV N protein highly likely lures the host translation apparatus for the preferential translation of viral mRNA during the course of infection, to boost the translation of viral mRNA in the infected cell. We will use multifaceted experimental avenues to test the hypothesis that CCHFV N protein interacts with the components of eIF4F complex to selectively engage the 40S ribosomal subunits on the viral mRNA 5’ UTR. Since ribosome loading on mRNA is a critical rate limiting step in eukaryotic translation, CCHFV N protein likely helps the viral transcripts at this critical step by selectively engaging the host cell ribosomes on viral mRNA 5’ UTR. This selective ribosome loading likely helps viral transcripts by avoiding the competition from host cell transcripts for the same host translation machinery. We will determine whether CCHFV N protein mediated translation strategy selectively facilitates the translation of viral mRNA during the course of infection.",,2024,Western University Of Health Sciences,423000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +P21877,1R01AI152241-01,Vaccines for Prevention of RG3 and RG4 Emerging Tickborne Viral Deseases,"PROJECT SUMMARY Tickborne illnesses continue to be a significant public health concern in the US and worldwide, as environmental and climate changes have allowed the dramatic expansion of ticks, tick habitats, and their mammalian hosts. In the New England region alone, Lone Star ticks were first reported in 2017, followed by the establishment of exotic Asian longhorned ticks in 2018. A recent CDC report indicates that tickborne diseases in the US have more than doubled from 2004 to 2016, accounting for 77% of all reported vector-borne diseases. The report also indicates that the US is not fully prepared to prevent and control these threats. A number of tickborne viruses that cause encephalitis and hemorrhagic fever in humans are of particular concern in the US, such as the re-emerging Powassan virus (POWV), as well as the recently discovered Heartland virus (HRTV). Another emerging tickborne virus in Asia is severe fever with thrombocytopenia syndrome virus (SFTSV), closely related to HRTV, which is transmitted by the Asian longhorned tick that is spreading rapidly and is now present in 12 US states. A number of additional exotic tickborne viral agents are of concern to the US, including tickborne encephalitis virus (TBEV), Omsk hemorrhagic fever virus (OHFV), and Crimean-Congo hemorrhagic fever virus (CCHFV). To better prepare for these emerging threats, we assembled a team of experts in (1) vaccine development at the University of Connecticut, (2) tickborne viruses at the Connecticut Agricultural Experiment Station, and (3) animal models in maximum biocontainment at the National Emerging Infectious Diseases Laboratories and propose the development and testing of vaccines for four Risk Group 3 (RG3) and RG4 tickborne encephalitis and hemorrhagic fever viruses classified as NIAID Category A or C Priority Pathogens, and prioritized by the WHO under its most recent 2018 Blueprint list of priority diseases in need of accelerated research and development. We developed a rapid method to generate vaccinia virus (VACV) vectors that will allow us to quickly test a number of tickborne viral genes to ensure robust expression of protective antigens and secretion of virus-like particles (VLPs). This platform is based on a gold-standard viral vector (VACV) that induces high levels of humoral and cell-mediated immune responses. These VACV vectors are replication-defective when administered as a vaccine, yet easy to propagate in standard cell culture at high titers, unlike other replication-defective poxvirus vectors such as MVA. We will also generate DNA- based vaccines and purified VLPs (as a subunit vaccine), so that three different classes of vaccine candidates can be tested for immunogenicity, either alone or in prime-boost regimens. Finally, we will test the efficacy of the vaccines using tick-transmission animal models to recapitulate the enhancement of transmission and dissemination that has been documented by tick feeding.",,2026,University Of Connecticut Storrs,526077,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Poxviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease models | Pre-clinical studies",2021 +P21881,5U01AI151698-02,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,1640909,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21882,3U01AI151698-02S2,University of Washington Arboviral Research Network (UWARN),"Abstract: University of Washington Arboviral Research Network (UWARN) The University of Washington Arboviral Research Network (UWARN) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Metacenter for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2022,University Of Washington,633625,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2021 +P21883,3U01AI151698-02S1,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,176500,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21884,1R21AI156406-01,Infection and prevalence of a new segmented flavivirus in the United States,"Summary/abstract Segmented RNA viruses that share phylogenetic relatedness with the prototypic Flaviviruses in their helicase (NS3) and polymerase (NS5) proteins were recently identified from ticks, mosquitoes, and vertebrates, including humans suffering with febrile illness. The first Flavi-like segmented viruses (FLSV) were isolated from ticks and animals in the Jingmen province of China and were thus named Jingmen Tick Virus. Subsequently, highly diverse FLSV variants were found in Africa, Europe and South America. However, no evidence of FLSV infection has been reported in North America, including the United States. Moreover, several recent studies that used metagenomics-based identification of the virome in ticks failed to identify FLSV infection. We were characterizing the virome of free-ranging mice of the genus Peromyscus, the most common wild mouse species of the North America, when we identified a highly diverse FLSV in several deer mice from woodlands in Pennsylvania (FLSV- PN). We acquired partial sequences of all five segments of the FLSV-PN genome and developed serological assays using Luciferase immunoprecipitation systems. Our serological data suggest that FLSV-PN or its related variants have a wide host range and infect several economically important farm and domestic animals. Most importantly, we found strong evidence of FLSV-PN infection in humans with a history of tick-bites and Lyme disease. The long-term goal of our exploratory/developmental proposal is to define the pathogenesis and health relevance of FLSV-PN infection. Development of molecular reagents for this new virus will allow us to test our hypotheses that several genetically diverse FLSV variants are circulating in the United States, and these viruses are predominantly transmitted by ticks to humans and animals. Specific aim-1 is to acquire the complete genomes of several diverse FLSV variants. Our preliminary data suggest that FLSV-PN genome is comprised of five RNA segments that are polyadenylated at the 3’ end. Complete genome sequencing of FLSV-PN is necessary for the development of sensitive and specific diagnostic assays to study infection prevalence and disease associations. Specific aim-2 is to determine the infection prevalence of FLSV in humans, domesticated animals and ticks. These studies will be aided by samples and data available from clinical research studies of Lyme disease at NIAID, NIH (letter of support attached). The proposed aims represent crucial steps toward detailed molecular and biological characterization of FLSV-PN, including the development of a reverse genetics system, replicon systems, cell culture and animal models. Although the health relevance of FLSV infections is currently not known, the proposed studies will inform this knowledge as well as develop the reagents for preventing the spread of this new virus and associated diseases, if necessary.",,2023,RESEARCH INST NATIONWIDE CHILDREN'S HOSP,246525,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2021 +P21887,1R01EY031894-01A1,NeuroEbola,"SUMMARY Ebolaviruses (EBOV) are among the deadliest pathogens known to man, with a case fatality rate of 25â€Â""90% depending on the outbreak. For the first time, monoclonal antibodies Zmapp, Mab114, REGN-EB3 and Remdesivir (inhibitor of viral RNA synthesis) were used, improving survival rates in Ebola treatment units (ETU) during the ongoing outbreak of Ebola virus disease (EVD) in Congo-Kinshasa. Despite treatments, 34% of EVD survivors experienced eye complications. In addition, they had lower [mean (SD)] minimental test examination (MMSE) scores i.e. [25 (5.5)] relative to controls [29.9 (0.6)] (p < 0.01); and women perform poorly [24.8 (5.90] relative to men [28.4 (3.2)](p < 0.01). The odds of depression were higher in EVD survivors [OR: 14.9 (95%CI: 4.4 â€Â"" 50.1)], mostly in women [OR: 4.4. (95%CI: 2.1 â€Â"" 9.6)] and, intriguingly, MMSE deficit in women was associated with higher initial EBOV viral load [OR: 0.84 (95%CI: 0.73 â€Â"" 0.98, p = 0.03, for one-unit increase in ctXptNP; lower ctXpt = higher viral load] after adjustment for age and depression status. EBOV persisted in breastmilk, wet preps, and semen for several months after acute EVD. We propose to test the hypothesis that occurrence of neuroophthalmologic sequalae is dictated by initial and/or persistence of EBOV viral load with discernable IgG responses, and/or a persistent inflammatory state driven by elevated cytokines and immune cell activation; by addressing the following specific aims: Aim 1. To contrast neuro- ophthalmologic deficits (spectrum & extent) found in confirmed EVD survivors to relevant profiles seen in their IgG+ but EVD-free close contacts, and IgG- controls (N = 90 per group). In Aim 1A, study participants will have longitudinal (0, 6, 12, 24, 36, and 48 month-time-points) assessments of neurocognition using the computerized Test of Variables of Attention (auditory and visual), the Test of Attentional Performance, and CogState for nonverbal cognitive skills. In Aim 1B, they will undergo psychophysical tests for visual acuity, contrast sensitivity, color vision, and visual field; as well as spectral domain-optical coherence tomography to elucidate structural biomarkers of disease within visual pathways. Aim differences levels overabundance 2 will determine whether group- on neuroophthalmologic outcomes found in Aim 1 are mediated by EBOV viral load or persistence, of anti-EBOV IgG, alterations in levels or activation status of circulating immune cells, and/or of proinflammatory cytokines. Aim 3 will enhance capacity in neurocognitive assessments, ophthalmologic evaluations and EVD immunoprofiling and molecular biology (RT-PCR). Gaps of knowledge to be filled include lack of understanding of (1) EBOV persistence, (2) long-lasting immune dysregulation, (3) IgG positivity with no overt EVD symptoms, all in contexts of post-EVD treatment. The overall goal of the proposed work aligns with the global health mission of the NIH while integrating the institute-specific missions of FIC, NEI, NIAID, NINDS, and the Office of Disease Prevention.",,2026,Oregon Health & Science University,601287,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P21889,5R41AI149940-02,Point-of-care antigen detection assay for early diagnosis of Ebola virus disease (EVD),"Project Summary Ebolavirus spp. cause a severe hemorrhagic fever known as Ebola virus disease (EVD). EVD is a serious public health concern, both as an emerging infectious disease and a potential biothreat. The 2013-2016 Ebola pandemic in West Africa brought global attention to the challenges associated with controlling an Ebola. The ongoing outbreak in the Democratic Republic of Congo, which recently reached over 1000 cases with no signs of slowing, has only confirmed the need for improved Ebola medical countermeasures. To better control Ebola outbreaks, it is imperative for healthcare workers to be able to diagnosis and isolate infected patients at the point-of-care in a timely manner. As such, the World Health Organization and other healthcare agencies have called for development of Ebola rapid diagnostic tests (RDTs). The proposed joint effort, for development a point-of-care antigen detection assay for early diagnosis of EVD, stems from a history of successful collaborations between the academic laboratory of Dr. David AuCoin at the University of Nevada, Reno (UNR) and commercial partner, InBios International, Inc. The two organizations have valuable expertise in RDT development and navigating the FDA approval process. The effort is further bolstered by assistance from collaborators at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) who will perform all high containment level (BSL4) studies. Preliminary studies for this proposal have resulted in an Ebola RDT prototype that shows a substantial improvement in sensitivity for Zaire ebolavirus. Our goal is to further improve assay sensitivity and expand detection to all EVD causing Ebolavirus spp. A comprehensive approach with clearly defined strategies will be used to support successful development of a pan-Ebola RDT with high sensitivity. Key aspects and milestones include: i) high throughput monoclonal antibody (mAb) production using multiple immunization strategies, ii) mAb characterization and RDT-based mAb screening, iii) commercial optimization and development of multiple assay prototypes, iv) determination of analytical sensitivity and specificity and v) assay validation with samples from Ebola-infected non-human primates.",,2024,"INBIOS INTERNATIONAL, INC.",298935,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21890,5R01AI148127-02,Emerging methods and applications for test-negative studies of of infectious disease interventions,"PROJECT SUMMARY/ABSTRACT The need for longitudinal follow-up of individuals exposed to interventions against rare infectious disease endpoints poses a barrier to prospective efficacy and effectiveness studies. Studies using the test-negative design (TND) have become a popular alternative. TNDs represent a variant on traditional case-control designs: studies enroll subjects who seek care for a clinical syndrome, defining those who test positive and negative for a pathogen of interest as “cases” and “controls”, respectively. To facilitate rigorous and reproducible assessments of vaccine performance, the project will re-assess emerging applications of the TND, and contribute methods to measure intervention effects from data collected by TND studies. The first two aims revisit estimation strategies for vaccine-conferred protection against infection and against the progression of infection to diseaseâ€Â""the two components of the vaccine “direct effect” that TND studies aim to measure. We propose novel frameworks to estimate each effect through extensions of the TND: one through comparisons of symptomatic and asymptomatic persons, and another leveraging the age distribution of cases. We will apply these methods to estimate pneumococcal conjugate vaccine effectiveness against vaccine-serotype pneumococcal pneumonia and carriage, and to re-assess reported differences in rotavirus vaccine effectiveness across high, middle, and low-income countries. In Aim 3, we will continue development of statistical procedures for cluster randomized test- negative designs. A major field trial of this nature for a vector intervention utilizing the bacterium Wolbachia to reduce dengue fever transmission is nearing completion. Permutation- based inference is planned because of small numbers of clusters. We will extend such methods (i) to allow for individual measures of intervention exposure (based on human and mosquito mobility), and (ii) to include design variants such as the stepped wedge design and interrupted time series where data collection has either recently ended or is in process. We will also consider a novel application to assess a new vaccine against Ebola Virus Disease (EVD) in the Democratic Republic of the Congo. This project will thus contribute methods and computational routines to allow valid inferences from TND study data, permitting novel assessments of interventions against rotavirus, pneumococcal disease, EVD, and dengue etc.",,2024,University Of California Berkeley,437670,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2020 +P21894,1R01AI153524-01A1,Immunological characterization of rationally-designed vaccines against plague in mice and non-human primate models,"ABSTRACT The increasing number of bubonic/pneumonic plague cases globally (2010-2018), including the U.S., with a ~18% case fatality rate may reflect climate changes and a rodent carrier range shift. The 2017-18 plague outbreak in Madagascar with ~2400 cases (>75% pneumonic) and ~9% causalities has led WHO (April 2018) to intensify the need for developing new generation subunit and live-attenuated plague vaccines. This need is exemplified by deadly plague cases in China (2019) and Congo (2020 with a 35% fatality rate). Y. pestis’ (Yp) ability to persist in dead hosts to resurge after years of silence, existence of antibiotic-resistant strains that occur naturally or have been intentionally developed, and no FDA-approved plague vaccine, is fearsome. Two- component subunit vaccines composed of capsular antigen F1 and a T3SS component and effector LcrV (low calcium response V antigen), which only generate a humoral immune response, provide variable protection in African green monkeys (AGM) and generate poor T cell responses in humans. Such vaccines will not be effective against Yp strains lacking F1 or possessing LcrV variants. Since the cellular immunity is also critical for protection, we focused first on identifying new virulence genes of Yp and then to delete them in combination to develop novel live-attenuated vaccine (LAV) strains. Two such LAVs were 100% attenuated in inducing bubonic/pneumonic plague in mice/rats and generated long-term humoral and cellular immune responses to provide 100% protection to rodents against developing plague. No clinical symptoms of the disease or histopathological lesions were noted either during immunization or when the vaccinated animals were subsequently exposed to Yp CO92 in a more stringent pneumonic plague model. Therefore, further immunological characterization of these mutants and their testing in higher animals, such as cynomolgus macaques (CM) and AGM, will provide a rationale for future clinical studies. There is a precedent for using a LAV against plague (EV76 strain) in humans. However, this vaccine is reactogenic, represents a spontaneous mutant, and causes disease in patients with over iron load. In Aim 1, we will demonstrate efficacy and immune responses of two vaccine candidates generated from Yp CO92 (biovar Orientalis) against other Yp biovars (Antiqua and Medievalis), the F1-minus mutant of CO92, and Yp CO92 with LcrV variants, in bubonic and pneumonic mouse models. Our data with the mutants indicated a role of IL-17 (a Th17 cytokine), Th1-IFN-γ, and antibodies, in protection. In Aim 2, we will study the mechanistic basis of this protection (one chosen mutant) by using RORt-/- mice, which lack Th17 cells, as well as IFN-γ and IgA k/o mice, to discern their links to neutrophil recruitment and mucosal immunity, to combat Yp infection in bubonic/pneumonic plague models. In Aim 3, CM and AGM will be used with one mutant to demonstrate its short- and long-term efficacy in causing bubonic and/or pneumonic plague as well as reactogenicity. The correlates of protective immunity will then be established. These innovative mechanistic/translational approaches will result in effective new generation plague vaccines.",,2025,University Of Texas Med Br Galveston,277816,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Vaccine design and administration",2021 +P21896,5R01AI153524-02,Immunological characterization of rationally-designed vaccines against plague in mice and non-human primate models,"ABSTRACT The increasing number of bubonic/pneumonic plague cases globally (2010-2018), including the U.S., with a ~18% case fatality rate may reflect climate changes and a rodent carrier range shift. The 2017-18 plague outbreak in Madagascar with ~2400 cases (>75% pneumonic) and ~9% causalities has led WHO (April 2018) to intensify the need for developing new generation subunit and live-attenuated plague vaccines. This need is exemplified by deadly plague cases in China (2019) and Congo (2020 with a 35% fatality rate). Y. pestis’ (Yp) ability to persist in dead hosts to resurge after years of silence, existence of antibiotic-resistant strains that occur naturally or have been intentionally developed, and no FDA-approved plague vaccine, is fearsome. Two- component subunit vaccines composed of capsular antigen F1 and a T3SS component and effector LcrV (low calcium response V antigen), which only generate a humoral immune response, provide variable protection in African green monkeys (AGM) and generate poor T cell responses in humans. Such vaccines will not be effective against Yp strains lacking F1 or possessing LcrV variants. Since the cellular immunity is also critical for protection, we focused first on identifying new virulence genes of Yp and then to delete them in combination to develop novel live-attenuated vaccine (LAV) strains. Two such LAVs were 100% attenuated in inducing bubonic/pneumonic plague in mice/rats and generated long-term humoral and cellular immune responses to provide 100% protection to rodents against developing plague. No clinical symptoms of the disease or histopathological lesions were noted either during immunization or when the vaccinated animals were subsequently exposed to Yp CO92 in a more stringent pneumonic plague model. Therefore, further immunological characterization of these mutants and their testing in higher animals, such as cynomolgus macaques (CM) and AGM, will provide a rationale for future clinical studies. There is a precedent for using a LAV against plague (EV76 strain) in humans. However, this vaccine is reactogenic, represents a spontaneous mutant, and causes disease in patients with over iron load. In Aim 1, we will demonstrate efficacy and immune responses of two vaccine candidates generated from Yp CO92 (biovar Orientalis) against other Yp biovars (Antiqua and Medievalis), the F1-minus mutant of CO92, and Yp CO92 with LcrV variants, in bubonic and pneumonic mouse models. Our data with the mutants indicated a role of IL-17 (a Th17 cytokine), Th1-IFN-γ, and antibodies, in protection. In Aim 2, we will study the mechanistic basis of this protection (one chosen mutant) by using RORt-/- mice, which lack Th17 cells, as well as IFN-γ and IgA k/o mice, to discern their links to neutrophil recruitment and mucosal immunity, to combat Yp infection in bubonic/pneumonic plague models. In Aim 3, CM and AGM will be used with one mutant to demonstrate its short- and long-term efficacy in causing bubonic and/or pneumonic plague as well as reactogenicity. The correlates of protective immunity will then be established. These innovative mechanistic/translational approaches will result in effective new generation plague vaccines.",,2025,University Of Texas Med Br Galveston,574886,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies | Vaccine design and administration",2021 +P21901,3U01AI151799-02S1,Emerging Infectious Diseases Research Center - East and Central Africa,"PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.",,2022,Washington State University,664517,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping",2021 +P21902,5U01AI151799-02,Emerging Infectious Diseases Research Center - East and Central Africa,"PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.",,2025,Washington State University,1512099,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping",2020 +P21903,1U01GH002319-01,"GH21-004, COVID-19 and related public health threats in populations affected by crises: a multi-disciplinary, collaborative research programme","Project summary / abstract In response to the Centers for Disease Control and Prevention’s Notice of Funding Opportunity to conduct research among crisis-affected and displaced populations in the context of COVID-19, we hereby propose a five- year programme of research and capacity strengthening , focussed on four key crisis-affected countries (the Democratic Republic of Congo, Somalia, South Sudan and Sudan), but with flexibility to conduct data collection in new emergencies and other settings where existing collaborations facilitate this. We present below a set of activities and studies organised along three aims: Aim 1: Establish or strengthen country-based, locally-led, multi-disciplinary humanitarian public health research units in the four key countries. Aim 2: Explore novel cross-cutting methods based on community-led surveillance and data science methods . Aim 3: Generate thematic evidence on the direct and indirect impacts of COVID-19 and other emergent public health threats, as per the following scientific objectives: 1. Generate improved all-cause and cause-specific 2. Quantify of SARS-CoV-2 and other epidemic infections. 3. Explore changes to behaviours, improve monitoring of hygiene behaviours and evaluate mortality estimates. transmission hygiene alternative behaviour change interventions. 4. Quantify and describe COVID-19’s secondary impacts on 5. Quantify COVID-19’s impacts on care models. sexual and reproductive health . non-communicable disease burden and mental health and test novel These activities will be undertaken by a consortium of academic institutions (the London School of Hygiene and Tropical Medicine, London, UK; the Université Catholique de Bukavu, DRC; SIMAD University, Mogadishu, Somalia; Imperial College London) and (the Bridge Network Organisation, South Sudan; the Sudan Youth Peer Network and Adeela for Art and Culture, Sudan). Our partnership is committed to co- production principles and will adopt a decolonial approach to research and humanitarian action. Most team members are former humanitarian workers, and all conduct the majority or all of their research work in or on crisis-affected populations. civil society actors",,2026,London School of Hygiene & Tropical Medicine,1000000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,United Kingdom,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Disease surveillance & mapping | Indirect health impacts,2022 +P21904,1U01GH002338-01,SICA Study: Seroepidemiological Insight into COVID-19 transmission in Africa,"PROJECT SUMMARY The COVID-19 pandemic has resulted in vastly different health outcomes for populations in Sub-Saharan Africa as compared to other countries with comparatively higher case numbers and deaths. The comparatively low numbers of cases and deaths reported in the Democratic Republic of Congo (DRC) and Nigeria, as well as throughout sub-Saharan Africa, are likely reflective of poor healthcare infrastructure and limited testing capacity. It is also unclear how the level of transmission of SARS-CoV-2 in urban vs. rural settings may influence COVID- 19 severity and the subsequent identification of cases by testing sites in both countries. Our overarching hypothesis is that prior exposure to related coronaviruses and other pathogens, which partition differentially in urban vs. rural communities, have resulted in significant cross-protective immunity or innate immune priming in the population, which leads to a reduced COVID-19 burden in these countries. We will leverage ongoing longitudinal cohort studies in urban and rural sites in the DRC and Nigeria, to support the characterization of: (i) the incidence of and risk factors for SARS-CoV-2 infection and COVID-19 severity, (ii) the current distribution and severity of respiratory/non-respiratory viral and non-viral pathogens as a cause of non-COVID-19 acute febrile illness, and (iii) role that exposure to syndemic pathogens have on COVID-19 severity. To this end, we propose to describe the incidence and prevalence of SARS-CoV-2 using seroepidemiology and describe factors associated with incidence and recovery (AIM1) and the epidemiology of respiratory and non-respiratory viral or parasitic pathogens viz. acute febrile illness (AFI) during the COVID-19 pandemic (AIM2). Our long-standing relationships through community engagement activities, and direct ties to the Public Health ministries as well as the Africa Centres for Disease Control allow us to obtain and convey accurate data at local resolution. We envision that this multinational surveillance project will provide much needed insight into the epidemiology of SARS-CoV-2 infection and COVID-19 disease in the DRC and Nigeria, elucidating differences in the incidence and disease outcomes across a range of urban vs. rural settings, which in turn can inform public health policy and control measures at country and regional levels.",,2026,University Of Florida,2000000,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2021 +P21910,5R43AI152672-02,Discovery of antiviral inhibitors of Ebola virus replication,"Ebola viruses (EBOV) cause severe illnesses in humans with a high rate of mortality that approaches 90%. Novel therapies with potent and selective activity against EBOV are urgently needed for the prevention and treatment of Ebola virus disease (EVD). We propose to execute an innovative high throughput screening campaign using a unique reverse genetics system. This screen is expected to yield new inhibitors targeting EBOV replication that will serve as starting points for medicinal chemistry hit-to-lead efforts. If successful, we will deliver one or more new lead series targeting EBOV infection.",,2022,"VENATORX PHARMACEUTICALS, INC.",300000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P21916,1U01AI151698-01,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2025,University Of Washington,1751002,Animals | Bacteria | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21917,3U01AI151698-01S1,University of Washington Arboviral Research Network (UWARN),"Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facilityâ€Â""based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.",,2022,University Of Washington,121420,Animals | Human Populations | Disease Vectors | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | Zika virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Pre-clinical studies",2020 +P21919,1R41AI149940-01,Point-of-care antigen detection assay for early diagnosis of Ebola virus disease (EVD),"Project Summary Ebolavirus spp. cause a severe hemorrhagic fever known as Ebola virus disease (EVD). EVD is a serious public health concern, both as an emerging infectious disease and a potential biothreat. The 2013-2016 Ebola pandemic in West Africa brought global attention to the challenges associated with controlling an Ebola. The ongoing outbreak in the Democratic Republic of Congo, which recently reached over 1000 cases with no signs of slowing, has only confirmed the need for improved Ebola medical countermeasures. To better control Ebola outbreaks, it is imperative for healthcare workers to be able to diagnosis and isolate infected patients at the point-of-care in a timely manner. As such, the World Health Organization and other healthcare agencies have called for development of Ebola rapid diagnostic tests (RDTs). The proposed joint effort, for development a point-of-care antigen detection assay for early diagnosis of EVD, stems from a history of successful collaborations between the academic laboratory of Dr. David AuCoin at the University of Nevada, Reno (UNR) and commercial partner, InBios International, Inc. The two organizations have valuable expertise in RDT development and navigating the FDA approval process. The effort is further bolstered by assistance from collaborators at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) who will perform all high containment level (BSL4) studies. Preliminary studies for this proposal have resulted in an Ebola RDT prototype that shows a substantial improvement in sensitivity for Zaire ebolavirus. Our goal is to further improve assay sensitivity and expand detection to all EVD causing Ebolavirus spp. A comprehensive approach with clearly defined strategies will be used to support successful development of a pan-Ebola RDT with high sensitivity. Key aspects and milestones include: i) high throughput monoclonal antibody (mAb) production using multiple immunization strategies, ii) mAb characterization and RDT-based mAb screening, iii) commercial optimization and development of multiple assay prototypes, iv) determination of analytical sensitivity and specificity and v) assay validation with samples from Ebola-infected non-human primates.",,2022,"INBIOS INTERNATIONAL, INC.",299112,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P21921,1R01AI148127-01A1,Emerging methods and applications for test-negative studies of of infectious disease interventions,"PROJECT SUMMARY/ABSTRACT The need for longitudinal follow-up of individuals exposed to interventions against rare infectious disease endpoints poses a barrier to prospective efficacy and effectiveness studies. Studies using the test-negative design (TND) have become a popular alternative. TNDs represent a variant on traditional case-control designs: studies enroll subjects who seek care for a clinical syndrome, defining those who test positive and negative for a pathogen of interest as “cases” and “controls”, respectively. To facilitate rigorous and reproducible assessments of vaccine performance, the project will re-assess emerging applications of the TND, and contribute methods to measure intervention effects from data collected by TND studies. The first two aims revisit estimation strategies for vaccine-conferred protection against infection and against the progression of infection to diseaseâ€Â""the two components of the vaccine “direct effect” that TND studies aim to measure. We propose novel frameworks to estimate each effect through extensions of the TND: one through comparisons of symptomatic and asymptomatic persons, and another leveraging the age distribution of cases. We will apply these methods to estimate pneumococcal conjugate vaccine effectiveness against vaccine-serotype pneumococcal pneumonia and carriage, and to re-assess reported differences in rotavirus vaccine effectiveness across high, middle, and low-income countries. In Aim 3, we will continue development of statistical procedures for cluster randomized test- negative designs. A major field trial of this nature for a vector intervention utilizing the bacterium Wolbachia to reduce dengue fever transmission is nearing completion. Permutation- based inference is planned because of small numbers of clusters. We will extend such methods (i) to allow for individual measures of intervention exposure (based on human and mosquito mobility), and (ii) to include design variants such as the stepped wedge design and interrupted time series where data collection has either recently ended or is in process. We will also consider a novel application to assess a new vaccine against Ebola Virus Disease (EVD) in the Democratic Republic of the Congo. This project will thus contribute methods and computational routines to allow valid inferences from TND study data, permitting novel assessments of interventions against rotavirus, pneumococcal disease, EVD, and dengue etc.",,2024,University Of California Berkeley,464409,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2020 +P21927,1U01AI151799-01,Emerging Infectious Diseases Research Center - East and Central Africa,"PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.",,2025,Washington State University,1529810,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping",2020 +P21928,1R56AI148284-01A1,Mathematical and Statistical Methods for the Control of Global Infectious Disease Threats,"Mathematical and Statistical Methods for the Control of Global Infectious Disease Threats ABSTRACT Outbreaks of emerging and re-emerging infectious diseases have become more frequent over time and pose a critical threat to human health. Pandemic and seasonal influenza, dengue and other arboviruses continue to spread on a global scale. Other specific infectious disease problems include Ebola, Lassa fever, plague, and Middle East Respiratory Syndrome (MERS-CoV). The consistent and rapid deployment of control measures, especially vaccines and antimicrobials, is crucial for reducing transmission and preventing or mitigating outbreaks caused by these infectious diseases. The goal of this research is to develop, validate, and implement novel mathematical and statistical techniques for modeling the transmission of major infectious disease threats. The resultant models will be applied to assess the impact of various layered control interventions and to guide the optimal allocation of resources for disease mitigation and control. Our specific aims correspond to this research challenge. (Aim 1) Develop innovative methods for mathematical modeling of important infectious disease threats. (Aim 2) To derive a portfolio of innovative statistical methods to improve estimation of key model parameters from surveillance data. (Aim 3) Optimize the use of layered interventions using the mathematical models. Overall, we will develop mathematical models with realistic transmission dynamics that achieve superior computational tractability. We will also derive statistical methods and apply these approaches to specific infectious disease threats. The output of our research will include comprehensive modeling results useful for understanding the transmission and control of the targeted infectious diseases. We hypothesize that the output of our research will provide a comprehensive analytic framework for understanding the transmission and control of the infectious diseases modeled, and to deal with future threats. The contribution of this research is significant because we will provide methods for modeling and analyzing the transmission and control of the significant infectious disease threats. The mathematical models with allow us to understand and predict the infectious disease transmission, and to devise optimal control strategies using vaccines, anti-microbial agents and non-pharmaceutical interventions. The statistical modeling will provide parameter estimation and fitting methods for the mathematical models, while the optimal control strategies devised will provide the decision method for the effective control of the infectious disease threats. This work be integrated into the infectious disease control efforts of the WHO Research and Development Blueprint for Action to Prevent Epidemics and the Emerging Pathogens Institute at the University of Florida. Our team has over 30 years of experience in this work, and it is uniquely positioned to conduct this research. The proposed work is innovative because it challenges existing paradigms on the integration of methods for the mathematical modeling and statistical analysis of infectious disease transmission into a comprehensive framework to determine the most effective combination of control measures for epidemic containment and mitigation.",,2022,University Of Florida,802262,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P21931,7R01EY029594-03,Pathogenesis of Uveitis in Ebola Virus Disease Survivors,"Project Summary/ Abstract Ebola virus disease (EVD) has been associated with a high prevalence of uveitis in EVD survivors in the wake of the unprecedented West African EVD outbreak from 2014-2016. The spectrum of disease ranges from anterior uveitis to sight-threatening panuveitis with complete blindness. The sheer number of EVD survivors impacted has given us the unique opportunity to characterize the clinical features, structural complications leading to vision loss, and pathogenesis of uveitis. Besides the significant impact of vision loss on quality-of- life and activities of daily living, uveitis associated with Ebola virus (EBOV) has scientific and public health implications because of our prior identification of EBOV in the aqueous humor. Beyond the recent outbreak in West Africa, two more recent outbreaks in Democratic Republic of Congo underscore the global health mandate to fully understand the clinical and scientific implications of EVD sequelae. Emerging clinical, basic, and translational investigation has provided insight regarding the potential mechanisms of uveitis associated with EVD. We recently described our novel methodology to safely interrogate aqueous humor specimens for EBOV in EVD survivors; while these ocular fluid specimens tested negative for EBOV by RT-PCR, recent molecular pathologic analysis of ocular tissue in a non-human primate EVD survivor model has demonstrated that EBOV persists within the vitreous humor in macrophages, and is associated with uveitis and retinitis. Additional compelling immunologic studies of an EVD survivor with uveitis showed Ebola-specific T-cell and B-cell activation with signs of ongoing Ebola antigen stimulation after plasma clearance of EBOV. These findings were suggestive of long-term EBOV persistence, which are detectable by systemic T- and B-cell responses. To further characterize the prevalence and clinical spectrum of uveitis, role of EBOV persistence and immunologic mechanisms of uveitis in EVD survivors, we propose three Aims: 1) In Aim 1, the prevalence of uveitis will be compared between EVD survivors and close contacts in Sierra Leone. Clinical factors and host risk factors including HLA-typing will be assessed to determine if there are clinical and host-related determinants of uveitis development. 2) In Aim 2, EBOV persistence will be assessed using reverse transcriptase polymerase chain reaction (RT- PCR testing) of vitreous fluid and in situ hybridization techniques to detect EBOV genome in the vitreous. 3) In Aim 3, Ebola-specific immune responses will be assessed in the blood and ocular fluid of EVD survivors with uveitis, specifically evaluating activation of Ebola-specific B and T-cells, IgG subclass composition. Insights from this study will define the spectrum of uveitis associated with EVD, assess whether EBOV is harbored in the vitreous, and advance our understanding of the interplay between infection and immunity in EVD. Ultimately, these findings will define diagnostic strategies and future medical countermeasures for EBOV, as well as other viruses that may establish persistence in the unique immune privileged ocular environment.",,2024,University Of Nebraska Medical Center,623030,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +P21934,1R43AI152672-01,Discovery of antiviral inhibitors of Ebola virus replication,"Ebola viruses (EBOV) cause severe illnesses in humans with a high rate of mortality that approaches 90%. Novel therapies with potent and selective activity against EBOV are urgently needed for the prevention and treatment of Ebola virus disease (EVD). We propose to execute an innovative high throughput screening campaign using a unique reverse genetics system. This screen is expected to yield new inhibitors targeting EBOV replication that will serve as starting points for medicinal chemistry hit-to-lead efforts. If successful, we will deliver one or more new lead series targeting EBOV infection.",,2022,"VENATORX PHARMACEUTICALS, INC.",300000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P21936,1R41AI174426-01,Development of recombinant VSV vaccines for emerging bunyaviruses,"PROJECT SUMMARY/ABSTRACT Emerging viral infections remain a global threat to human health. Bunyaviruses are the largest order of RNA viruses that includes many clinically relevant human pathogens such as Lassa, Rift Valley Fever and various hantaviruses which cause viral hemorrhagic fever (VHF). SFTSV, or Severe fever with thrombocytopenia syndrome virus, is an emerging tick-borne bunyavirus that has caused outbreaks in Eastern Asia (China, Japan, Korea, Vietnam) with up to a 30% case fatality rate. The host tick vector has now been discovered over a large geographical setting and SFTSV has been found in numerous wild and domestic animal species highlighting a risk for zoonotic spillover into humans. Though humans are usually dead-end hosts, human to human transmission has been documented through blood and mucosal secretions. Furthermore, SFTSV has a segmented genome which increases ability to reassort genes and mutate. Due to these features, in its 2017 “Research and Development Blueprint” the WHO identified SFTSV as one of 11 pathogens likely to cause a sever outbreak in the future. As we have learned, from experience with recent zoonotic outbreaks, preparedness is of the utmost importance. We are proposing to continue development of a recombinant vesicular stomatitis virus (rVSV)-based vaccine for SFTSV. rVSV is an approved vaccination platform that is immunogenically potent and proven tolerable. Preliminary work from our group has demonstrated that rVSV-SFTSV can elicit protection in mice, is tolerable in immunocompromised animals and upon CNS injection, and can generate cross protecting responses to a related bunyavirus. Furthermore, we observe elevated SFTSV-specific T cell and antibody responses against both SFTSV spike proteins, Gn and Gc. In this Phase I, we propose to improve the design of our vector which will increase viral titers to facilitate vaccine manufacturing and increase immunogenicity in animals. In aim 1, we will focus on reverse engineering mutations into rVSV that will improve SFTSV Gn/Gc incorporation into particles thereby improving virus replication and yield in vitro. We will characterize these 2nd generation (Gen2) vaccines using molecular and cell-based assays scoring for viral replication, GnGc expression in infected cells and incorporation of GnGc in VSV virions. In aim 2, we will assess the ability of our Gen2 vaccine to protect animals in lethal SFTSV challenge studies. We hypothesize that increased GnGc expression and replication of the Gen2 vectors will lead to improved immune responses in vaccinated animals compared to the Gen1 vector. We will assess immune correlates of protection such enhanced neutralizing and cross protective antibodies as well as robust T cell responses compared to Gen1 rVSV-SFTSV vaccinated animals. If successful, our Phase I would set the foundation for a Phase II to advance manufacturing and stringently study protective capacity of our vaccine in more advanced animal models.",,2025,"ADVAC THERAPEUTIC, LLC",255454,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P21937,1R16AI167830-01A1,In vivo relevance of the Schlafen-mediated innate immune mechanism in flavivirus infection,"ABSTRACT Flaviviruses are important human pathogens including viruses such as West Nile, dengue, and Zika. No specific treatments or vaccines are available against these infections, and no biomarkers exist that allow predicting their outcome, characterized by important clinical variability. Understanding innate antiviral immune responses against flaviviruses, could lead to the identification of disease susceptibility biomarkers and therapeutic targets. We recently demonstrated that the type I interferon-stimulated protein Schlafen 11 (SLFN11) is a novel and potent flavivirus restriction factor. In this application we aim to define, at the molecular level, several aspects of the mechanism of action of SLFN11 and determine the anti-flavivirus activity of other members of the SLFN family, as well as the in vivo relevance of this defense system. Therefore, this investigation is highly relevant and will significantly advance our understanding of the antiviral mechanism of action of SLFN proteins, which is currently unknown.",,2027,University Of Texas El Paso,151360,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P21938,1R21AI178550-01,Pre-clinical evaluation of alpha-Cache; a novel RNA vaccine for an emerging orthobunyavirus,"Abstract Orthobunyaviruses are an understudied genus in the order Bunyavirales that has no vaccines or therapies in clinical development. One of the prototype pathogens within this genus, as recently identified by NIAID, is Cache Valley virus (CVV). CVV is an emerging arthropod-borne virus that induces spontaneous abortions and congenital malformations in ruminants and humans. Given CVV’s prevalence and its broad host range, coupled with the expanding geographical range of its diverse array of competent vectors, the epidemic potential of CVV continues to increase, reminiscent of what was previously observed for Chikungunya and Zika viruses. To date, there have been no reported vaccine development activities for this virus, and prototype approaches are urgently needed to develop road maps for vaccines against viruses within this genus should an epidemic occur in the future. With the rapid adoption of mRNA vaccine technology during the ongoing COVID-19 pandemic, coupled with the recent emergency use approval of HDT Bio’s self-amplifying mRNA vaccine platform, we propose to apply HDT’s technology to develop prototype vaccines for the orthobunyavirus genus with a proof-of-concept vaccine to prevent CVV infection in a novel murine model of CVV infection and disease. This innovative, timely, and critically important R21 aims to study the safety profile and protective efficacy of this vaccine, and identify the important antigens required for broad cross-reactive immunity post-vaccination, via two specific aims: 1. Evaluate the safety, immunogenicity, and optimal dosage regimen for a LIONTM-formulated, replicon- RNA vaccine for CVV. 2. Investigate the efficacy and correlates of protection of a LION-formulated, replicon-RNA vaccine for preventing CVV-induced disease in murine models. Considering a One Health approach, and recognizing the connection between the health of humans and animals, such a vaccine could have an immediate impact in the veterinary/agricultural market, simultaneously preventing economic damage, animal disease, and disease emergence in humans. In the event of epidemic emergence in humans, this approach could be rapidly adapted and scaled for human trials.",,2025,VIRGINIA POLYTECHNIC INST AND ST UNIV,262294,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P21939,5R03AI156580-02,ARBOVIRUS CIRCULATION AND DIVERSITY OF MOSQUITO VECTORS ACROSS HABITATS IN THE GAMBIA,"Project Summary/Abstract This application seeks to examine arbovirus and mosquito vector prevalence and identify their possible influence in The Gambia. An existing infrastructure in the country for malaria investigation will jumpstart this project. Like malaria, mosquito-borne arboviruses can cause febrile illness; with significant morbidity and even mortality, in multiple regions of the world. Practically nothing is known about the arboviruses that circulate in The Gambia; except for three instances: an outbreak of Yellow Fever over forty years ago, localized antibody evidence of Zika virus, and two one-off cases of Rift Valley fever. Arboviral activity of this unique country is poorly understood. Importantly, there are cases of acute febrile illness in The Gambia that are not attributable to malaria, and we hypothesize that arboviruses are circulating in the region that could be responsible for a proportion of such cases. In addition, there is a paucity of data on local mosquito populations, other than the Anopheline vectors of malaria, and potential vectors of arboviruses. Incrimination of mosquito species responsible for natural arbovirus transmission is pivotal to understanding pathogen dynamics and designing precise vector control strategies. To enhance response to emerging public health threats in The Gambia, the proposed research aims to address gaps in the knowledge of mosquito-borne arboviruses and their vectors by: (a) sampling mosquitoes in The Gambia (utilizing a framework already in place for malaria monitoring, with extended sampling locations) to contrast vector species communities in different landscapes during both the dry and rainy seasons, and to assess arboviral evidence to determine mosquito infection rates across regions; and (b) evaluating vector species diversity and abundance, as well as predictors of the risk of detected mosquito species and arboviruses, considering their prevalence in association with seasonality, macroclimate, and landscape development. Vector and arbovirus presence can, in future, be compared to potential geographic prevalence of human cases. When fever is not caused by malaria, local epidemiology, including a baseline knowledge of what arboviruses and their vectors are circulating in a region, can guide medical decisions. The proposed research is both significant and novel because it addresses the lack of understanding of arbovirus existence in a previously unstudied country, one that is experiencing unexplained cases of acute febrile illness. Although neighboring Senegal has been noted for an arboviral presence, The Gambia has a separate geography, public health system, and political setting, and is unexplored in this respect. Non-malarial febrile illness occurs in The Gambia, and we propose initial steps for investigating arboviruses as potential etiological agents, allowing for improved understanding of infectious disease agents. We aim to generate preliminary data for studies of arboviruses threatening health in The Gambia and, ultimately, facilitating targeted prevention of arboviral pathogens (as well as malaria) and a more streamlined approach to addressing vector-borne disease burden.",,2024,VIRGINIA POLYTECHNIC INST AND ST UNIV,63000,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector biology | Disease transmission dynamics,2021 +P21940,1R03AI156580-01A1,ARBOVIRUS CIRCULATION AND DIVERSITY OF MOSQUITO VECTORS ACROSS HABITATS IN THE GAMBIA,"Project Summary/Abstract This application seeks to examine arbovirus and mosquito vector prevalence and identify their possible influence in The Gambia. An existing infrastructure in the country for malaria investigation will jumpstart this project. Like malaria, mosquito-borne arboviruses can cause febrile illness; with significant morbidity and even mortality, in multiple regions of the world. Practically nothing is known about the arboviruses that circulate in The Gambia; except for three instances: an outbreak of Yellow Fever over forty years ago, localized antibody evidence of Zika virus, and two one-off cases of Rift Valley fever. Arboviral activity of this unique country is poorly understood. Importantly, there are cases of acute febrile illness in The Gambia that are not attributable to malaria, and we hypothesize that arboviruses are circulating in the region that could be responsible for a proportion of such cases. In addition, there is a paucity of data on local mosquito populations, other than the Anopheline vectors of malaria, and potential vectors of arboviruses. Incrimination of mosquito species responsible for natural arbovirus transmission is pivotal to understanding pathogen dynamics and designing precise vector control strategies. To enhance response to emerging public health threats in The Gambia, the proposed research aims to address gaps in the knowledge of mosquito-borne arboviruses and their vectors by: (a) sampling mosquitoes in The Gambia (utilizing a framework already in place for malaria monitoring, with extended sampling locations) to contrast vector species communities in different landscapes during both the dry and rainy seasons, and to assess arboviral evidence to determine mosquito infection rates across regions; and (b) evaluating vector species diversity and abundance, as well as predictors of the risk of detected mosquito species and arboviruses, considering their prevalence in association with seasonality, macroclimate, and landscape development. Vector and arbovirus presence can, in future, be compared to potential geographic prevalence of human cases. When fever is not caused by malaria, local epidemiology, including a baseline knowledge of what arboviruses and their vectors are circulating in a region, can guide medical decisions. The proposed research is both significant and novel because it addresses the lack of understanding of arbovirus existence in a previously unstudied country, one that is experiencing unexplained cases of acute febrile illness. Although neighboring Senegal has been noted for an arboviral presence, The Gambia has a separate geography, public health system, and political setting, and is unexplored in this respect. Non-malarial febrile illness occurs in The Gambia, and we propose initial steps for investigating arboviruses as potential etiological agents, allowing for improved understanding of infectious disease agents. We aim to generate preliminary data for studies of arboviruses threatening health in The Gambia and, ultimately, facilitating targeted prevention of arboviral pathogens (as well as malaria) and a more streamlined approach to addressing vector-borne disease burden.",,2023,VIRGINIA POLYTECHNIC INST AND ST UNIV,62350,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector biology | Disease transmission dynamics,2021 +P21941,1R21AI180853-01,"Illuminating Lujo virus glycoprotein structure, receptor engagement and neutralizing antibody epitopes","Project Summary The Mammarenavirus genus of the Arenavirus family contains multiple zoonotic pathogens with the potential to cause hemorrhagic fever. These include the South American viruses Junin virus (JUNV; Argentinian hemorrhagic fever) and Machupo virus (MACV; Bolivian hemorrhagic fever), and Lassa virus (LASV), which causes thousands of cases of Lassa Fever in West Africa each year. The case fatality rate for these viruses is 20-70%. Lujo virus (LUJV) is the most recently identified African arenavirus. This virus was responsible for five infections, of which four were fatal. Notably, this outbreak was characterized by human-to-human transmission rather than transmission between rodent and human, as is most common for other arenaviruses. Arenaviruses are genetically and geographically divided into New World (e.g. JUNV and MACV) and Old World (e.g. LASV) groups. Its African location placed LUJV into the OW group. However, LUJV is genetically divergent from other African arenaviruses and is phylogenetically equidistant between the NW and OW groups. Further, its glycoprotein GPC recognizes a different receptor and is antigenically distinct from the other arenaviruses. As the only protein expressed on the viral surface, GPC is responsible for receptor engagement, cell tropism and entry, and is the primary target of antibodies. Understanding the unique structure and surface chemistry of LUJV GPC in its native conformation is key to understanding receptor recognition in the native trimer context, what antibody targets might be on this divergent virus, and how we might design vaccines and therapeutics should the virus re-emerge. The premise of this proposal is that structures of the medically relevant LUJV GP alone and in complex with its cell surface receptor will reveal reasons for its unique cell entry requirements and any differences in its epitope landscape. We will use state-of-the-art biophysical techniques such as cryo electron microscopy, surface plasmon resonance and composition-gradient multiangle light scattering, to characterize the interaction of the prefusion-stabilized LUJV GP trimer (pfGP-TD) with its receptor NRP2. In Aim 2, we will identify antibodies from mice immunized with LUJV pfGP-TD using the Berkeley Lights Beacon platform. Results from the innovative research proposed here will launch multiple lines of inquiry for future studies and will help guide development of vaccines against a diverse range of arenaviruses.",,2025,LA JOLLA INSTITUTE FOR IMMUNOLOGY,247050,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2023 +P21942,4R00AI156012-03,Viral factors responsible for Lassa virus pathogenicity,"Lassa virus (LASV) is endemic in West African countries and causes outbreaks of LF annually. Although LASV is one of the most alarming pathogens from a public health perspective, there are few effective vaccines or therapeutics against LF. LASV must be handled at biosafety level 4 (BSL-4), due to its high pathogenicity. This is one of the largest barriers to the development of preventive or therapeutic approaches against LF. Furthermore, animal models of LF are limited, which is essential for basic research and development of countermeasures. Recently, we developed a novel guinea pig model of LF and found that LASV strain LF2384 and LF2350 have completely different pathogenic phenotypes in guinea pigs. These two viruses have been isolated from human LF patients and pathogenicity of these viruses in guinea pigs is consistent with human cases. These unique combinations of immunocompetent rodent model and clinical isolated LASVs are strong tools, which allow us to reveal viral factors responsible for pathogenicity and molecular mechanisms underlying LASV pathogenicity. During K99 phase, we revealed that RNA-dependent RNA polymerase (L) is the determinant factor of pathogenic differences between LASV LF2384 and LF2350 by using the reverse genetic system and in vivo evaluation. While significant progress has been made in determining the pathogenic viral factor, much less is understood about the host response related to LASV pathogenesis. Therefore, in the proposed study, we will determine host factors responsible for LASV pathogenicity by using reverse genetics and in vivo experiments, and reveal novel molecular mechanisms of LASV L protein underlying LASV pathogenesis by using several in vitro molecular techniques. We will address this goal through three specific aims. In Specific Aim 1, we will reveal the pathophysiology of LASV infection in guinea pigs. In Specific Aim 2, we will determine the domain or amino acid residue(s) in L responsible for LASV pathogenicity by using reverse genetics and in vivo study. In Specific Aim 3, we will unveil molecular mechanisms underlying LASV pathogenicity. Taken together, we hope to address novel pathogenic mechanisms of LASV infection, leading to new insights to develop countermeasures against LF.",,2025,University Of Texas Med Br Galveston,249000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2021 +P21943,5R21AI166985-02,Novel Function(s) of Arenavirus NP Exoribonuclease,"PROJECT SUMMARY/ABSTRACT Several mammalian arenaviruses cause severe and fatal zoonotic diseases in humans, for which vaccines and treatments are very limited. Lassa virus (LASV) is the causative agent for Lassa fever (LF) that is currently endemic in Western Africa. Despite its importance to public health, important knowledge gaps still exist in the basic biology for LASV and other highly pathogenic arenaviruses, partly due to the limitation of high containment BSL4 facilities required for infection experiments. The RNA synthesis of RNA virus is generally error prone as viral RNA-dependent RNA polymerase lacks proofreading activity. As negative-sense RNA virus, how arenavirus ensures proper RNA synthesis is largely unclear. The LASV nucleoprotein has a DEDDH 3' to 5' exoribonuclease motif (ExoN), of which its function in virus life cycle is still a puzzle. The current paradigm in the field is that the NP ExoN activity efficaciously degrades virus-derived double-stranded RNA and is the key to LASV evasion of innate immunity. Intriguingly, the ExoN motif is highly conserved in NPs of all arenaviruses, regardless of pathogenicity. Therefore, it is very likely that the NP ExoN has important but yet-to-be-identified function(s) in arenavirus replication in addition to immune evasion. In this project, we aim to define the important role(s) of arenavirus NP ExoN in virus replication. Our preliminary data indicated that: 1). Loss of NP ExoN activity resulted in aberrant genomic RNA production and a drastic reduction in LASV RNA level in IFN-deficient cells; and 2). Loss of NP ExoN activity increased LASV sensitivity to mutagenic nucleoside analogue treatment. We propose that LASV NP ExoN promotes proper viral RNA synthesis, controls aberrant viral genomic RNA formation and/or ensures the fidelity of viral RNA replication. To define the impact of NP ExoN on the integrity and functionality of viral genomic RNA, we will explore to utilize an innovative long-read sequencing technology to systematically investigate the sequence and abundancy of genomic RNAs at single molecule level. Arenavirus has been known to form defective interfering particles, which regulates virus infection in vivo and in vitro. The molecular basis for DI genome remains elusive due to technical obstacle. The long-read sequencing technology may enable us to identify DI candidates and the potential role of NP ExoN in regulating DI formation. We will also investigate whether arenavirus NP ExoN has proofreading activity that ensures the fidelity of viral RNA replication. At the end of this project, we may discover novel and important function(s) of arenavirus NP ExoN in virus life cycle and move the field forward. Using LASV as a model, we may better understand how arenavirus virus ensures proper viral RNA synthesis. With the novel long-read sequencing technology, this study may overcome technical barrier and increase our knowledge on basic virology of pathogenic arenaviruses. The data may open up new directions. For instance, future studies on the mechanisms underlying the important roles of NP ExoN are warranted. This project may also facilitate antiviral development by targeting NP ExoN activity.",,2024,University Of Texas Med Br Galveston,200000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P21944,5R21AI169789-02,Designing mammarenavirus live vaccines with unbreachable attenuation,"Project Summary/Abstract The mammarenavirus Lassa (LASV) is endemic to West Africa where it infects several hundred thousand individuals yearly resulting in a high number of Lassa fever (LF) cases associated with high morbidity and mortality. There are no US FDA-approved LASV vaccines and current anti-LASV therapy is limited to an off-label use of ribavirin that has limited efficacy. LF has been included on the revised list of priority diseases for the WHO R&D Blueprint, underscoring an urgent need for vaccines to combat LF. Epidemiological studies indicate that a live-attenuated vaccine (LAV) represents the most feasible approach to control LF. Mammarenaviruses are enveloped viruses with a bi-segmented negative strand RNA genome. Each genome segment contains two open reading frames separated by a non-coding intergenic region (IGR). The large (L) segment encodes the RNA dependent RNA polymerase, L protein, and the Z matrix protein, whereas the small (S) segment encodes the surface glycoprotein precursor (GPC) and nucleoprotein (NP). We have documented that recombinant (r) forms of the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) expressing a codon deoptimized (CD) GPC or containing the IGR of the S segment in both the S and L segments rLCMV/IGR(S-S) are stable and fully attenuated in mice but able to provide complete protection, upon a single administration, against a subsequent lethal challenge with WT LCMV. Importantly, we have replicated these findings with LASV, thus validating the use of LCMV to generate proof of concept results to guide studies with LASV. The central goal of this application is to test the hypothesis that an rLCMV combining the features of a CD GPC and the S-IGR in both S and L genome segments, hereinafter rLCMV/IGR-CD, will have excellent safety and protective efficacy features as LAV, and an unbreachable attenuation. To test our hypothesis, we will assess the safety, immunogenicity, and protective efficacy of rLCMV/IGR-CD (Aim 1) and examine whether rLCMV/IGR-CD prevents, in co-infected mice, the generation of LCMV reassortants with increased virulence (Aim 2), as well as evaluate rLCMV/IGR-CD stability during multiple rounds of infection in FDA approved for production of human vaccines Vero E6 cells and in vivo (Aim 3).",,2024,"SCRIPPS RESEARCH INSTITUTE, THE",221875,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P21945,5R01AI171438-02,"Genetic, structural and functional profiling of the human antibody response to arenavirus infection","PROJECT SUMMARY Arenaviruses are a family of zoonotic RNA viruses that are capable of causing severe hemorrhagic fever disease in humans. Lassa virus (LASV), an Old World arenavirus which is endemic in regions of West Africa including Sierra Leone and is the causative agent of Lassa fever (LF), causes thousands of deaths annually. Arenaviruses have repeatedly crossed over into humans over the past several decades, and emerging variants of known arenaviruses often display increased human-to-human transmissibility and broader geographic range. For these reasons, the CDC and WHO have classified several human arenaviruses as high priority pathogens and the PREDICT consortium ranked LASV as the highest risk virus on their watchlist of potential pandemic pathogens. Vaccines and therapeutics against arenaviruses are urgently needed, however, we must first gain a much deeper understanding of the molecular mechanisms that result in protective humoral immunity. Although the discovery of effective clinical countermeasures is the ultimate goal, this collaborative project focuses on leveraging innovative, high-throughput antibody discovery and characterization tools to define the genetic, functional and structural properties of anti-LASV antibodies with broad specificity across human arenaviruses. We have assembled a collaborative, multidisciplinary group of investigators with a long history of productive collaboration in viral immunology and with complementary areas of expertise. Additionally, we have access to a singular cohort of LF survivors at Kenema Government Hospital, which is located in Sierra Leone and is at the heart of the LF zone. We expect our work will result in the discovery of thousands of novel anti-LASV antibodies, characterization of which will reveal conserved sites of viral vulnerability and uncover the precise molecular mechanisms of viral neutralization. These fundamental studies directly address critical gaps in our understanding of the interplay between humoral immunity and hemorrhagic fever-causing arenaviruses and will serve as a foundation for future translational studies. ",,2027,"SCRIPPS RESEARCH INSTITUTE, THE",870348,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P21946,5K99AI156012-02,Viral factors responsible for Lassa virus pathogenicity,"PROJECT SUMMARY/ABSTRACT This career development award will help fill in the knowledge and skills in basic virological research of Risk Group 4 agents, which need to be handled in the highest containment laboratory (BSL-4). This is essential for the goal to become an independent researcher as an expert on highly pathogenic infectious diseases. The goal during the award period is to reveal novel mechanisms of Lassa fever (LF) by using both in vivo and in vitro techniques, leading to new insight into the development of countermeasures and controlling methods against Lassa fever. Lassa virus (LASV) is endemic in West African countries and causes outbreaks of LF annually. Although LASV is one of the most alarming pathogens from a public health perspective, there are few effective vaccines or therapeutics against LF. LASV must be handled at biosafety level 4 (BSL-4), due to its high pathogenicity. This is one of the largest barriers to the development of preventive or therapeutic approaches against LF. Furthermore, animal models of LF are limited, which is essential for basic research and development of countermeasures. Recently, we developed a novel guinea pig model of LF and found that LASV strain LF2384 and LF2350 have completely different pathogenic phenotypes in guinea pigs. These two viruses have been isolated from human LF patients and pathogenicity of these viruses in guinea pigs is consistent with human cases. These unique combinations of immunocompetent rodent model and clinical isolated LASVs are strong tools, which allow us to reveal viral factors responsible for pathogenicity and molecular mechanisms underlying LASV pathogenicity. In the proposed study, we will determine factors responsible for LASV pathogenicity and reveal novel molecular mechanisms underlying LASV infection by using reverse genetics, in vivo experiments, and several in vitro molecular techniques. We will address this goal through three specific aims. In Specific Aim 1, we will reveal the pathophysiology of LASV infection in guinea pigs. In Specific Aim 2, we will determine viral factors responsible for LASV pathogenicity by using reverse genetics and in vivo study. In Specific Aim 3, we will unveil molecular mechanisms underlying LASV pathogenicity. Taken together, we hope to address novel pathogenic mechanisms of LASV infection, leading to new insights to develop countermeasures against LF.",,2023,University Of Texas Med Br Galveston,63240,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2021 +P21947,5U3RAI156433-02,Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model,"Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model ABSTRACT: Lassa fever (LF) is caused by infection with Lassa virus (LASV), and is currently a major human disease problem in much of West Africa, causing thousands of deaths annually. Recent outbreaks of LF have been characterized by an increased number of cases and larger geographic footprint compared to previous outbreaks, and constitute a burgeoning public health crisis. In addition, the number of LF cases imported into non-endemic countries is growing, and there is also concern that LASV could be used as an agent of biological warfare. There is as yet no licensed vaccine or specific antiviral therapeutic to intervene against LASV-infections and treat patients with LF, and current treatment options have poor efficacy. There is therefore an immediate and critical medical need for new antiviral compounds to address LASV. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are a class of single-stranded-nucleic acid analogs that can enter cells readily and interfere with the production of viral proteins through steric blocking of complementary RNA. PPMO have shown considerable antiviral efficacy in vitro and in vivo against a number of RNA viruses, including several arenaviruses. We propose to synthesize two PPMO targeting highly conserved RNA sequences in the genomic termini of the LASV genome. Each PPMO will be tested in a non-cytotoxic dose-range for antiviral activity against several genetically- disparate strains of LASV. The PPMO exhibiting the highest antiviral efficacy in vitro will then be advanced to testing in a guinea pig model of LASV disease. Animal weight, temperature, appearance and behavior, along with mortality and viral titer in several tissues will be monitored. This study is designed to evaluate the ability of PPMO to reduce morbidity and mortality in a small-animal model of of severe LASV-disease. If successful, the project will produce an inhibitor that would be immediately useful as a research reagent against any strain of LASV and as a candidate for further development as a therapeutic agent against LASV infections in humans.",,2024,Oregon State University,74250,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21948,1R21AI166985-01A1,Novel Function(s) of Arenavirus NP Exoribonuclease,"PROJECT SUMMARY/ABSTRACT Several mammalian arenaviruses cause severe and fatal zoonotic diseases in humans, for which vaccines and treatments are very limited. Lassa virus (LASV) is the causative agent for Lassa fever (LF) that is currently endemic in Western Africa. Despite its importance to public health, important knowledge gaps still exist in the basic biology for LASV and other highly pathogenic arenaviruses, partly due to the limitation of high containment BSL4 facilities required for infection experiments. The RNA synthesis of RNA virus is generally error prone as viral RNA-dependent RNA polymerase lacks proofreading activity. As negative-sense RNA virus, how arenavirus ensures proper RNA synthesis is largely unclear. The LASV nucleoprotein has a DEDDH 3' to 5' exoribonuclease motif (ExoN), of which its function in virus life cycle is still a puzzle. The current paradigm in the field is that the NP ExoN activity efficaciously degrades virus-derived double-stranded RNA and is the key to LASV evasion of innate immunity. Intriguingly, the ExoN motif is highly conserved in NPs of all arenaviruses, regardless of pathogenicity. Therefore, it is very likely that the NP ExoN has important but yet-to-be-identified function(s) in arenavirus replication in addition to immune evasion. In this project, we aim to define the important role(s) of arenavirus NP ExoN in virus replication. Our preliminary data indicated that: 1). Loss of NP ExoN activity resulted in aberrant genomic RNA production and a drastic reduction in LASV RNA level in IFN-deficient cells; and 2). Loss of NP ExoN activity increased LASV sensitivity to mutagenic nucleoside analogue treatment. We propose that LASV NP ExoN promotes proper viral RNA synthesis, controls aberrant viral genomic RNA formation and/or ensures the fidelity of viral RNA replication. To define the impact of NP ExoN on the integrity and functionality of viral genomic RNA, we will explore to utilize an innovative long-read sequencing technology to systematically investigate the sequence and abundancy of genomic RNAs at single molecule level. Arenavirus has been known to form defective interfering particles, which regulates virus infection in vivo and in vitro. The molecular basis for DI genome remains elusive due to technical obstacle. The long-read sequencing technology may enable us to identify DI candidates and the potential role of NP ExoN in regulating DI formation. We will also investigate whether arenavirus NP ExoN has proofreading activity that ensures the fidelity of viral RNA replication. At the end of this project, we may discover novel and important function(s) of arenavirus NP ExoN in virus life cycle and move the field forward. Using LASV as a model, we may better understand how arenavirus virus ensures proper viral RNA synthesis. With the novel long-read sequencing technology, this study may overcome technical barrier and increase our knowledge on basic virology of pathogenic arenaviruses. The data may open up new directions. For instance, future studies on the mechanisms underlying the important roles of NP ExoN are warranted. This project may also facilitate antiviral development by targeting NP ExoN activity.",,2024,University Of Texas Med Br Galveston,240000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P21949,1R21AI169789-01A1,Designing mammarenavirus live vaccines with unbreachable attenuation,"Project Summary/Abstract The mammarenavirus Lassa (LASV) is endemic to West Africa where it infects several hundred thousand individuals yearly resulting in a high number of Lassa fever (LF) cases associated with high morbidity and mortality. There are no US FDA-approved LASV vaccines and current anti-LASV therapy is limited to an off-label use of ribavirin that has limited efficacy. LF has been included on the revised list of priority diseases for the WHO R&D Blueprint, underscoring an urgent need for vaccines to combat LF. Epidemiological studies indicate that a live-attenuated vaccine (LAV) represents the most feasible approach to control LF. Mammarenaviruses are enveloped viruses with a bi-segmented negative strand RNA genome. Each genome segment contains two open reading frames separated by a non-coding intergenic region (IGR). The large (L) segment encodes the RNA dependent RNA polymerase, L protein, and the Z matrix protein, whereas the small (S) segment encodes the surface glycoprotein precursor (GPC) and nucleoprotein (NP). We have documented that recombinant (r) forms of the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) expressing a codon deoptimized (CD) GPC or containing the IGR of the S segment in both the S and L segments rLCMV/IGR(S-S) are stable and fully attenuated in mice but able to provide complete protection, upon a single administration, against a subsequent lethal challenge with WT LCMV. Importantly, we have replicated these findings with LASV, thus validating the use of LCMV to generate proof of concept results to guide studies with LASV. The central goal of this application is to test the hypothesis that an rLCMV combining the features of a CD GPC and the S-IGR in both S and L genome segments, hereinafter rLCMV/IGR-CD, will have excellent safety and protective efficacy features as LAV, and an unbreachable attenuation. To test our hypothesis, we will assess the safety, immunogenicity, and protective efficacy of rLCMV/IGR-CD (Aim 1) and examine whether rLCMV/IGR-CD prevents, in co-infected mice, the generation of LCMV reassortants with increased virulence (Aim 2), as well as evaluate rLCMV/IGR-CD stability during multiple rounds of infection in FDA approved for production of human vaccines Vero E6 cells and in vivo (Aim 3).",,2024,"SCRIPPS RESEARCH INSTITUTE, THE",266250,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P21950,1F31AI172358-01,Evaluation of structural conservation and glycan-mediated host receptor engagement of pan-lineage Lassa fusion glycoproteins by cryo-EM,"Project Summary/Abstract: Recognized as a priority emerging pathogen by the World Health Organization due to its potential to cause a public health crisis and the absence of efficacious therapeutics or vaccines,1 Lassa fever affects an estimated 300,000 people per year and results in approximately 5000 deaths.2 Lassa virus (LASV)â€Â""a member of the Arenaviridae familyâ€Â""presents heavily glycosylated envelope glycoprotein complexes (GPC) which are the focus of many preclinical vaccine studies. The trimeric conformation of GPC is necessary to induce almost all neutralizing antibody responses in immunization studies3; however, the solubilized ectodomain is inherently unstable and has proved recalcitrant to unbound structural studies in the past.4 Our recent work describes the development of a trimerization scaffold positioned at the membrane proximal region of GPC which stabilizes the protein in its trimeric form. This project will use this platform to describe native-like, representative GPCs from across LASV lineages and structurally explore their interactions with host cell receptors. I hypothesize the high-resolution LASV structures will show conserved epitopes, especially at their receptor-binding regions, which will be used to guide next-generation immunogen design and induce more robust and neutralizing humoral responses. I will test this hypothesis through three primary aims: 1) solving the representative high-resolution, apo structures of LASV GPC across lineages by single- particle cryo-EM, 2) identifying the key residues which facilitate binding with GPC host cell receptors, and 3) developing a suite of stable, soluble GPC trimers representative of clinically relevant LASV strains. I expect the results of these aims will demonstrate conserved GPC epitopes which facilitate neutralizing immune responses will be predominantly quaternary in nature, which has thus far been largely undescribed in the literature due to the instability of the GPC trimer. During this process, I will receive comprehensive training in structural biology, virology, and immunology from my interdisciplinary mentors. The additional professional development resources at the Scripps Research Institute and in the broader San Diego area will ensure I develop the skills needed for my long-term goal of directing a research lab in emerging pathogen vaccine development.",,2023,"SCRIPPS RESEARCH INSTITUTE, THE",33752,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +P21951,1R01AI171438-01,"Genetic, structural and functional profiling of the human antibody response to arenavirus infection","PROJECT SUMMARY Arenaviruses are a family of zoonotic RNA viruses that are capable of causing severe hemorrhagic fever disease in humans. Lassa virus (LASV), an Old World arenavirus which is endemic in regions of West Africa including Sierra Leone and is the causative agent of Lassa fever (LF), causes thousands of deaths annually. Arenaviruses have repeatedly crossed over into humans over the past several decades, and emerging variants of known arenaviruses often display increased human-to-human transmissibility and broader geographic range. For these reasons, the CDC and WHO have classified several human arenaviruses as high priority pathogens and the PREDICT consortium ranked LASV as the highest risk virus on their watchlist of potential pandemic pathogens. Vaccines and therapeutics against arenaviruses are urgently needed, however, we must first gain a much deeper understanding of the molecular mechanisms that result in protective humoral immunity. Although the discovery of effective clinical countermeasures is the ultimate goal, this collaborative project focuses on leveraging innovative, high-throughput antibody discovery and characterization tools to define the genetic, functional and structural properties of anti-LASV antibodies with broad specificity across human arenaviruses. We have assembled a collaborative, multidisciplinary group of investigators with a long history of productive collaboration in viral immunology and with complementary areas of expertise. Additionally, we have access to a singular cohort of LF survivors at Kenema Government Hospital, which is located in Sierra Leone and is at the heart of the LF zone. We expect our work will result in the discovery of thousands of novel anti-LASV antibodies, characterization of which will reveal conserved sites of viral vulnerability and uncover the precise molecular mechanisms of viral neutralization. These fundamental studies directly address critical gaps in our understanding of the interplay between humoral immunity and hemorrhagic fever-causing arenaviruses and will serve as a foundation for future translational studies. ",,2027,"SCRIPPS RESEARCH INSTITUTE, THE",887255,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P21952,1U3RAI156433-01,Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model,"Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model ABSTRACT: Lassa fever (LF) is caused by infection with Lassa virus (LASV), and is currently a major human disease problem in much of West Africa, causing thousands of deaths annually. Recent outbreaks of LF have been characterized by an increased number of cases and larger geographic footprint compared to previous outbreaks, and constitute a burgeoning public health crisis. In addition, the number of LF cases imported into non-endemic countries is growing, and there is also concern that LASV could be used as an agent of biological warfare. There is as yet no licensed vaccine or specific antiviral therapeutic to intervene against LASV-infections and treat patients with LF, and current treatment options have poor efficacy. There is therefore an immediate and critical medical need for new antiviral compounds to address LASV. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are a class of single-stranded-nucleic acid analogs that can enter cells readily and interfere with the production of viral proteins through steric blocking of complementary RNA. PPMO have shown considerable antiviral efficacy in vitro and in vivo against a number of RNA viruses, including several arenaviruses. We propose to synthesize two PPMO targeting highly conserved RNA sequences in the genomic termini of the LASV genome. Each PPMO will be tested in a non-cytotoxic dose-range for antiviral activity against several genetically- disparate strains of LASV. The PPMO exhibiting the highest antiviral efficacy in vitro will then be advanced to testing in a guinea pig model of LASV disease. Animal weight, temperature, appearance and behavior, along with mortality and viral titer in several tissues will be monitored. This study is designed to evaluate the ability of PPMO to reduce morbidity and mortality in a small-animal model of of severe LASV-disease. If successful, the project will produce an inhibitor that would be immediately useful as a research reagent against any strain of LASV and as a candidate for further development as a therapeutic agent against LASV infections in humans.",,2023,Oregon State University,74250,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21953,1K99AI156012-01A1,Viral factors responsible for Lassa virus pathogenicity,"PROJECT SUMMARY/ABSTRACT This career development award will help fill in the knowledge and skills in basic virological research of Risk Group 4 agents, which need to be handled in the highest containment laboratory (BSL-4). This is essential for the goal to become an independent researcher as an expert on highly pathogenic infectious diseases. The goal during the award period is to reveal novel mechanisms of Lassa fever (LF) by using both in vivo and in vitro techniques, leading to new insight into the development of countermeasures and controlling methods against Lassa fever. Lassa virus (LASV) is endemic in West African countries and causes outbreaks of LF annually. Although LASV is one of the most alarming pathogens from a public health perspective, there are few effective vaccines or therapeutics against LF. LASV must be handled at biosafety level 4 (BSL-4), due to its high pathogenicity. This is one of the largest barriers to the development of preventive or therapeutic approaches against LF. Furthermore, animal models of LF are limited, which is essential for basic research and development of countermeasures. Recently, we developed a novel guinea pig model of LF and found that LASV strain LF2384 and LF2350 have completely different pathogenic phenotypes in guinea pigs. These two viruses have been isolated from human LF patients and pathogenicity of these viruses in guinea pigs is consistent with human cases. These unique combinations of immunocompetent rodent model and clinical isolated LASVs are strong tools, which allow us to reveal viral factors responsible for pathogenicity and molecular mechanisms underlying LASV pathogenicity. In the proposed study, we will determine factors responsible for LASV pathogenicity and reveal novel molecular mechanisms underlying LASV infection by using reverse genetics, in vivo experiments, and several in vitro molecular techniques. We will address this goal through three specific aims. In Specific Aim 1, we will reveal the pathophysiology of LASV infection in guinea pigs. In Specific Aim 2, we will determine viral factors responsible for LASV pathogenicity by using reverse genetics and in vivo study. In Specific Aim 3, we will unveil molecular mechanisms underlying LASV pathogenicity. Taken together, we hope to address novel pathogenic mechanisms of LASV infection, leading to new insights to develop countermeasures against LF.",,2023,University Of Texas Med Br Galveston,113977,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2021 +P21954,3R01AI139238-03S1,Defining the role of phosphatidylserine in hemorrhagic fever virus replication,"Project Summary Ebola virus (EBOV) and Lassa virus (LASV) infection is enhanced when cells express phosphatidylserine (PS) binding receptors on the cell surface. PS is a cellular lipid normally restricted to the inner leaflet, or cytoplasmic face, of the cellular plasma membrane (PM). The restriction of PS and other phospholipids to the inner leaflet produces a highly asymmetric membrane in healthy cells. PS is flipped to the outer leaflet of the cellular membrane during calcium signaling and apoptosis, marking them as activated or dying cells, respectively. Cellular enzymes termed flippases and scramblases are responsible for flipping the PS in the membrane. PS is incorporated into the viral membrane during virus budding, when EBOV and LASV particles appropriate a portion of the host cell's plasma membrane as a protective envelope. In order to engage PS receptors, the PS on a viral envelope must be flipped to the outer leaflet. We aim to elucidate the mechanism by which viral envelopes obtain properly oriented PS, as well as the amount of PS sufficient to interact with PS receptors. We are using a panel of human haploid (HAP1) cell lines lacking PS flippases or PS scramblases to examine the role these proteins play in the replication of EBOV and LASV. We produced vesicular stomatitis virus containing either its native glycoprotein (G), LASV-GP, or EBOV-GP, enabling us to perform experiments under BSL2 conditions. When these recombinant viruses were grown in the HAP1 knock-out cell lines, we identified one flippase and one scramblase that are required for efficient spread of VSV particles containing either the LASV-GP or EBOV-GP, but not VSV-G. This data suggests altering the levels of PS in the outer leaflet of the cellular PM inhibits one or more steps in the viral replication cycle. Virus-like particles resembling either EBOV or LASV were found to contain less surface PS when produced in cells deficient in scramblase activity, also supporting our overall hypothesis that cellular enzymes involved in the production and localization of PS will impact EBOV and LASV entry and spread. We have proposed three specific aims to further examine the role PS plays in viral replication: Aim 1: Examine the requirements for cellular scramblase activity in EBOV and LASV entry and virion production; Aim 2: Examine the requirements for cellular flippase activity in EBOV and LASV entry; Aim 3: Determine the effects of altered cellular PS to EBOV and LASV replication and the viral lipid profile. Using VSV-based pseudoparticles in addition to virus-like EBOV particles and recombinant lymphocytic choriomeningitis virus (rLCMV) containing the LASV-GP, we will determine the role of cellular flippases and scramblases during viral replication, and confirm our results using similar experiments with authentic virus in a BSL4 lab. Experiments will also define the lipidome of these viruses and approaches will focus on quantifying the levels of modified PS on viral particles. Understanding the role PS and other lipids play on LASV and EBOV infectivity will potentially provide new targets for future antivirals.",,2023,University Of Georgia,73742,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P21957,1F31AI154700-01,Mechanisms of cell entry of Lymphocytic Choriomeningitis Virus.,"Project Summary Arenaviruses are zoonotic negative-sense RNA viruses closely associated with specific rodent hosts (1). Some of these viruses, however, are known to cause human disease such as Lassa, Lymphocytic Choriomeningitis Virus (LCMV), LuJo, Machupo, and Junín virus (6). The prototypic arenavirus that belongs to the Old World (OW) clade, Lymphocytic Choriomeningitis Virus (LCMV), infects house mice (Mus musculus) and consequently has a worldwide distribution (7, 8, 9, 10). While LCMV infection in humans is typically asymptomatic or associated with mild illness, it can also cause abortions, congenital birth defects, and has been implicated in mortality of transplant recipients (11, 12, 13, 14, 15). Moreover, LCMV infection of mice has proven to be an exceptionally effective model system for the study of virus-host interactions, which has led to seminal discoveries in the fields of microbiology and immunology (16, 17, 18). The glycoprotein complex (GPC) of arenaviruses mediates virus entry into cells culminating in membrane fusion. The first arenavirus receptor to be discovered was alpha- dystroglycan (α-DG) for the Old World viruses LASV and LCMV, and the Clade C New World arenaviruses Olivero and Latino (19, 25). Previous work by us and others revealed that LASV entry was more complicated than previously appreciated. Through the use of haploid genetic screens, the virus was found to rely on Lysosomal Associated Membrane Protein 1 (LAMP1), in an α-DG-independent manner (28, 29). Lassa virus attaches to glycosylated α-DG at neutral pH at the cell surface, and upon endocytic uptake and trafficking to endosomal and lysosomal cell compartments, the GPC undergoes an acid pH-induced transition to engage lysosomal membrane protein LAMP1 and drive membrane fusion (29). To date, the entry process LCMV remains incompletely understood. LCMV has been reported to infect efficiently in the absence of its published receptor, α-DG, nor is infection reliant upon LAMP1, suggesting that critical entry factor(s) remain unknown (20, 21, 29). To identity unknown factors involved in LCMV entry, we did a preliminary genome-wide CRISPR-Cas9 screen and identified CD164, a lysosomal protein, as the most significant hit. This preliminary data led us to hypothesize that upon endocytic transport of LCMV to lysosomal compartments, LCMV GP engages CD164, which then facilitates acid pH-dependent membrane fusion. Here, we propose to use genetic, cell biological, biochemical, and structural studies to characterize the role of CD164 in LCMV entry. The first aim is to determine the host genes required for cell entry of LCMV through the use of a CRISPR-Cas9 genome-wide loss-of-function screen, followed by validation of significant hits through individual genetic knockouts and lentiviral addbacks. The second aim is to probe the mechanism by which CD164 facilitates entry of LCMV by determining the domain within CD164 and its necessary glycosylation through genetic manipulation of cells, as well as biochemical and structural approaches to characterize the interaction between LCMV GP and CD164.",,2023,HARVARD MEDICAL SCHOOL,39035,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P21959,7R21AI135284-03,Attenuation of Lassa Virus Via Codon Deoptimization,"Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose a serious public health problem in their endemic regions. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly in West Africa resulting in a high number of Lassa fever (LF) cases associated with high morbidity and mortality. Notably, increased traveling has led to the importation of LF cases into non-endemic metropolitan areas around the globe. Besides their impact in public health, several arenaviruses, including LASV, have features that make them a credible biodefense threat. There are no FDA-licensed vaccines to combat arenavirus infections and current anti-arenaviral therapy is limited to the off-label use of ribavirin, which is only partially effective and associated with side effects. The significance of arenaviruses, including LASV, in human health and biodefense readiness, together with the limited existing armamentarium to combat their infections, highlight the importance of developing effective vaccines to combat arenavirus induced disease in humans. The central goal of this application is to test the novel hypothesis that a codon deoptimized (CD)-based strategy can be used for the development of a safe, immunogenic, stable and protective live-attenuated vaccines (LAV) to combat HF disease caused by LASV infection. Moreover, we also hypothesize that a recombinant LASV expressing a codon deoptimized (CD) glycoprotein (GP), rLASV/GPCD, will prove investigators with a valid LASV surrogate that could be safely used in BSL2 facilities to facilitate the investigation of LASV-host cell interactions as well as the identification and characterization of anti- LASV candidate therapeutics without the need of BSL4 containment, currently needed to work with live forms of this important human biodefense pathogen. The bases for our hypothesis are: 1) Existing evidence that CD can be used to generate attenuated viruses, including arenaviruses, that are able to provide protection against a challenge with wild-type (WT) virus. 2) CD LAV have identical immunogenic properties than WT virus, but the large number (>100s) of silent mutations within the genome of CD LAV makes impossible its reversion to a virulent strain. 3) CD LAV, including arenaviruses, are able to grow to high titers, compatible with vaccine production, in FDA-approved Vero cells for vaccine production. 4) Generation of CD recombinant LASV can be rapidly achieved using our state-of-the-art reverse genetics technologies. To test our hypothesis, we will first use the prototypic LCMV system that provides us with an excellent reference virus that can be safely used in BSL2 facilities to test whether a CD LASV GP can convert a virulent strain into an attenuated (Aim 1) and stable (Aim 2) form still able to induce protective immunity (Aim 3) using the well characterized mouse model of LCMV infection. We will use this knowledge to generate a rLASV/GPCD whose potential as LAV will be evaluated using the well-established guinea pig model of LF disease (Aim 4).",,2021,TEXAS BIOMEDICAL RESEARCH INSTITUTE,144892,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P21961,5U01IP001157-03,"IP21-002, Enhanced Surveillance to Assess Vaccine Preventable Enteric and Respiratory Virus Illnesses","We will conduct active, prospective inpatient, emergency department (ED) and asymptomatic healthy control (HC) surveillance in children at SCH and affiliated clinics in the Seattle metropolitan area. We will enroll subjects to describe the population-based burden of AGE and ARI in King County and Snohomish County, WA and evaluate effectiveness of licensed vaccines, such as influenza (Flu) and rotavirus (RV) vaccine (vx). We will assess the epidemiology and natural history of pediatric respiratory and enteric viral diseases and assess transmission dynamics for vx-preventable (RV, Flu) and potentially vx-preventable pathogens, such as norovirus (NV), respiratory syncytial virus (RSV), and SARS-CoV-2. After obtaining informed consent and assent, if applicable, in English or Spanish, we will interview families to collect epidemiological and clinical information, vaccine history, and obtain study specimens including respiratory and/or stool specimens, depending on clinical symptoms. Vaccination data are recorded in our state vaccine database, which is very reliable and complete. During times of COVID-19, novel methods of enrollment and capturing data may be utilized as per IRB- approved protocols including verbal or online consent, telephone interviews to complete data capture, and home specimen collection. Respiratory specimens and stool samples will be tested for multiple respiratory and enteric pathogens using sensitive and specific molecular PCR tests in laboratories using approved testing strategies that have been validated by proficiency testing. With this information, in addition to publicly available state-wide data describing inpatient and acute care visits in WA, we will obtain incidence rates of ED and inpatient visits and characterization of illness for multiple viral pathogens, including those responsible for vx- preventable disease and potentially vx-preventable disease, and others related to acute respiratory and enteric diseases, such as rhinovirus, EVD-68, parainfluenza viruses, adenoviruses, and human metapneumovirus. Additionally, we will continue ongoing surveillance for Acute Flaccid Myelitis (AFM) throughout WA state. In collaboration with statewide AFM expert and SCH neurologist, Dr. Catherine Otten and using WA DOH surveillance data we will conduct active surveillance, establish incidence rates, and compare rates of AFM to current circulation of respiratory and gastrointestinal infections. We will characterize the clinical spectrum of AFM by evaluating clinical and laboratory data, MRI findings, therapeutic interventions, and outcomes to inform early diagnosis, prognosis, prevention, and treatment.",,2026,SEATTLE CHILDREN'S HOSPITAL,2749994,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2021 +P21964,5U01IP001157-02,"IP21-002, Enhanced Surveillance to Assess Vaccine Preventable Enteric and Respiratory Virus Illnesses","We will conduct active, prospective inpatient, emergency department (ED) and asymptomatic healthy control (HC) surveillance in children at SCH and affiliated clinics in the Seattle metropolitan area. We will enroll subjects to describe the population-based burden of AGE and ARI in King County and Snohomish County, WA and evaluate effectiveness of licensed vaccines, such as influenza (Flu) and rotavirus (RV) vaccine (vx). We will assess the epidemiology and natural history of pediatric respiratory and enteric viral diseases and assess transmission dynamics for vx-preventable (RV, Flu) and potentially vx-preventable pathogens, such as norovirus (NV), respiratory syncytial virus (RSV), and SARS-CoV-2. After obtaining informed consent and assent, if applicable, in English or Spanish, we will interview families to collect epidemiological and clinical information, vaccine history, and obtain study specimens including respiratory and/or stool specimens, depending on clinical symptoms. Vaccination data are recorded in our state vaccine database, which is very reliable and complete. During times of COVID-19, novel methods of enrollment and capturing data may be utilized as per IRB- approved protocols including verbal or online consent, telephone interviews to complete data capture, and home specimen collection. Respiratory specimens and stool samples will be tested for multiple respiratory and enteric pathogens using sensitive and specific molecular PCR tests in laboratories using approved testing strategies that have been validated by proficiency testing. With this information, in addition to publicly available state-wide data describing inpatient and acute care visits in WA, we will obtain incidence rates of ED and inpatient visits and characterization of illness for multiple viral pathogens, including those responsible for vx- preventable disease and potentially vx-preventable disease, and others related to acute respiratory and enteric diseases, such as rhinovirus, EVD-68, parainfluenza viruses, adenoviruses, and human metapneumovirus. Additionally, we will continue ongoing surveillance for Acute Flaccid Myelitis (AFM) throughout WA state. In collaboration with statewide AFM expert and SCH neurologist, Dr. Catherine Otten and using WA DOH surveillance data we will conduct active surveillance, establish incidence rates, and compare rates of AFM to current circulation of respiratory and gastrointestinal infections. We will characterize the clinical spectrum of AFM by evaluating clinical and laboratory data, MRI findings, therapeutic interventions, and outcomes to inform early diagnosis, prognosis, prevention, and treatment.",,2026,SEATTLE CHILDREN'S HOSPITAL,1933284,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2021 +P21966,5R03AI148754-02,Reproductive health sequelae in women who survived Ebola Virus Disease in Sierra Leone and Liberia,"SUMMARY STATEMENT The growing body of research on Ebola virus disease (EVD) suggests that female survivors of the virus may be at increased risk of miscarriage or stillbirth in new pregnancies conceived after recovery from acute EVD-infection. In addition, recent reports suggest that the Ebola virus may persist in the uteruses of survivors who were pregnant during acute Ebola infection (PDAEI) and that the virus may become reactivated during subsequent pregnancies, creating the potential for pregnant survivors to spread the virus to others, long after they have recovered from initial acute EVD infection. Previous research on pregnancies in female EVD survivors have not explored associations between pregnancy outcomes after EVD with pregnancy history prior to EVD or whether or not the woman was PDAEI. Understanding the post-EVD pregnancies of survivorsâ€Â"" especially those who were PDAEI and may be vulnerable to viral recrudescenceâ€Â""is a critical first step in assessing risk of EVD’s re-emergence after outbreaks. The proposed study will compare the incidence and outcomes of pregnancies conceived post- EVD among: PDAEI EVD survivors, non-PDAEI EVD survivors, and a comparison group. This proposed study will utilize self-reported, questionnaire-based data from female EVD survivors and other women of reproductive age (comparison group) in Liberia and Sierra Leone and is currently being collected through an NIH-funded R01 study (NIAID #1R01AI123535-01A1). The specific aims of this study are: 1) to estimate the incidence of recognized pregnancies conceived after Ebola by EVD-survivors; and 2) among women with a recognized pregnancy after Ebola, to estimate the incidence of failed pregnancy reported by EVD-survivors and to describe host and disease-specific factors associated with pregnancy outcomes. This study has the potential to expand our understanding of how, if at all, EVD may differentially impact the post-EVD pregnancies of survivors, including those who were PDAEI. Results may be used to inform guidelines for the management of EVD in pregnant women and management of pregnancy in EVD survivors.",,2022,FAMILY HEALTH INTERNATIONAL,68510,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P21967,1U01IP001157-01,"IP21-002, Enhanced Surveillance to Assess Vaccine Preventable Enteric and Respiratory Virus Illnesses","We will conduct active, prospective inpatient, emergency department (ED) and asymptomatic healthy control (HC) surveillance in children at SCH and affiliated clinics in the Seattle metropolitan area. We will enroll subjects to describe the population-based burden of AGE and ARI in King County and Snohomish County, WA and evaluate effectiveness of licensed vaccines, such as influenza (Flu) and rotavirus (RV) vaccine (vx). We will assess the epidemiology and natural history of pediatric respiratory and enteric viral diseases and assess transmission dynamics for vx-preventable (RV, Flu) and potentially vx-preventable pathogens, such as norovirus (NV), respiratory syncytial virus (RSV), and SARS-CoV-2. After obtaining informed consent and assent, if applicable, in English or Spanish, we will interview families to collect epidemiological and clinical information, vaccine history, and obtain study specimens including respiratory and/or stool specimens, depending on clinical symptoms. Vaccination data are recorded in our state vaccine database, which is very reliable and complete. During times of COVID-19, novel methods of enrollment and capturing data may be utilized as per IRB- approved protocols including verbal or online consent, telephone interviews to complete data capture, and home specimen collection. Respiratory specimens and stool samples will be tested for multiple respiratory and enteric pathogens using sensitive and specific molecular PCR tests in laboratories using approved testing strategies that have been validated by proficiency testing. With this information, in addition to publicly available state-wide data describing inpatient and acute care visits in WA, we will obtain incidence rates of ED and inpatient visits and characterization of illness for multiple viral pathogens, including those responsible for vx- preventable disease and potentially vx-preventable disease, and others related to acute respiratory and enteric diseases, such as rhinovirus, EVD-68, parainfluenza viruses, adenoviruses, and human metapneumovirus. Additionally, we will continue ongoing surveillance for Acute Flaccid Myelitis (AFM) throughout WA state. In collaboration with statewide AFM expert and SCH neurologist, Dr. Catherine Otten and using WA DOH surveillance data we will conduct active surveillance, establish incidence rates, and compare rates of AFM to current circulation of respiratory and gastrointestinal infections. We will characterize the clinical spectrum of AFM by evaluating clinical and laboratory data, MRI findings, therapeutic interventions, and outcomes to inform early diagnosis, prognosis, prevention, and treatment.",,2026,SEATTLE CHILDREN'S HOSPITAL,1441645,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2021 +P21969,1R03AI148754-01,Reproductive health sequelae in women who survived Ebola Virus Disease in Sierra Leone and Liberia,"SUMMARY STATEMENT The growing body of research on Ebola virus disease (EVD) suggests that female survivors of the virus may be at increased risk of miscarriage or stillbirth in new pregnancies conceived after recovery from acute EVD-infection. In addition, recent reports suggest that the Ebola virus may persist in the uteruses of survivors who were pregnant during acute Ebola infection (PDAEI) and that the virus may become reactivated during subsequent pregnancies, creating the potential for pregnant survivors to spread the virus to others, long after they have recovered from initial acute EVD infection. Previous research on pregnancies in female EVD survivors have not explored associations between pregnancy outcomes after EVD with pregnancy history prior to EVD or whether or not the woman was PDAEI. Understanding the post-EVD pregnancies of survivorsâ€Â"" especially those who were PDAEI and may be vulnerable to viral recrudescenceâ€Â""is a critical first step in assessing risk of EVD’s re-emergence after outbreaks. The proposed study will compare the incidence and outcomes of pregnancies conceived post- EVD among: PDAEI EVD survivors, non-PDAEI EVD survivors, and a comparison group. This proposed study will utilize self-reported, questionnaire-based data from female EVD survivors and other women of reproductive age (comparison group) in Liberia and Sierra Leone and is currently being collected through an NIH-funded R01 study (NIAID #1R01AI123535-01A1). The specific aims of this study are: 1) to estimate the incidence of recognized pregnancies conceived after Ebola by EVD-survivors; and 2) among women with a recognized pregnancy after Ebola, to estimate the incidence of failed pregnancy reported by EVD-survivors and to describe host and disease-specific factors associated with pregnancy outcomes. This study has the potential to expand our understanding of how, if at all, EVD may differentially impact the post-EVD pregnancies of survivors, including those who were PDAEI. Results may be used to inform guidelines for the management of EVD in pregnant women and management of pregnancy in EVD survivors.",,2022,FAMILY HEALTH INTERNATIONAL,68510,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P21972,1R21AI180822-01,In vivo engineering of chimeric antibody reprogrammed (CAR) B cells with fully tunable antibody response,"The longstanding paradigm in vaccine development has been the introduction of immunogens that culminates in generation of pathogen-binding antibodies (Ab). While the precise format of the antigen presentation differs, all vaccines rely on somatic hypermutation of immunoglobulin genes in B cells to generate Ab with greater affinity, avidity or anti-pathogen activity. Unfortunately, the natural variations in our immune system leads to highly variable Ab responses, both in magnitude of the induced Ab response and the breadth/potencies of the specific Ab clones generated, resulting in variable efficacy. Here, we seek to overcome these shortcomings by directly reprogramming circulating B cells to secrete specific potent Ab of interest, including stable integration of Ab-encoding transgenes into circulating B-cells. The resulting chimeric antibody reprogrammed (CAR) B cells can produce Ab with magnitude, affinity and effector functions that can all be controlled with molecular/genetic specificity. We refer to this as in vivo engineering of CAR-B cells. The key to realizing this vision is a delivery platform that can facilitate highly specific transduction of B- cells in vivo. We have engineered lentivirus (LV) vectors that effectively transduce circulating immune cells. Our first-generation system achieved highly specific transduction of circulating T-cells even at very low virus:cell ratio, and generated substantial CAR-T cells in the circulation and in tumor of immune-deficient NSG mice with highly aggressive BV173 lymphoma, leading to effective suppression of the tumor and prolonged survival. We have since improved upon our first-generation system with a second-generation LV system incorporating the Nipah virus fusion protein. Nipah LV (NLV), coupled with a proprietary combo of transduction enhancers (TE), efficiently and specifically transduced non-activated B-cells in human PBMCs. In pilot studies, a single injection of NLV+TE into NSG mice with circulating human PBMCs lead to effective transduction of >0.5% of all circulating B-cells. We have also demonstrated we can harness CRISPR/Cas9 to insert Ab transgene into a well conserved site in B cells, leading to functional B cells that can react to antigens. In this proposal, we seek to perform key enabling studies that substantiate our proposed CAR-B strategy. In Aim 1, we will engineer NLV that targets different B-cell populations, and identify the combination of NLV and TE that maximizes transduction of key human B-cells. We will then assess delivery of transgene encoding for a potent RSV neutralizing Ab (nAb) either by non-specific integration or site-specific integration. We will then advance into animal studies in Aim 2, where we will assess transduction efficiency and specificity in NSG mice infused with circulating human PBMCs. We will quantify for the levels of the nAb in serum over time, and assess protection against infection by respiratory syncytial virus (RSV). If successful, our work will advance an alternative strategy for achieving highly tunable immune protection in cases where specificity of the variable domain or Ab isotype is essential, or in individuals who do not respond to traditional vaccination.",,2025,UNIV OF NORTH CAROLINA CHAPEL HILL,209925,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Characterisation of vaccine-induced immunity,2024 +P21973,5UM1AI148574-05,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,556480,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2020 +P21974,5R21AI169561-02,Functional genomic characterization of diverse bat innate immune mechanisms,"PROJECT SUMMARY Human health can be inextricably linked to our understanding of bats, as bats are known or predicted reservoirs for the precursors of many zoonotic viruses. Unfortunately, we still know little about bat immunology, and we do not know what characteristics allow them to survive with the same viruses that can readily kill other hosts such as humans. This problem is exacerbated by the fact that bats are an incredibly diverse order of mammals, so what we learn about the immunological mechanisms of one bat species may not be true for another. We need new techniques and technologies to efficiently explore the vast unknown universe of immunological mechanisms that exist across diverse bats. In this application, we propose to develop key tools needed to functionally characterize the genetic underpinnings of bat immunology. In the first aim, we propose to pair modern advances in recombinant DNA synthesis and cell engineering to more comprehensively investigate the function of orthologous genes already proposed to be important in bat immune homeostasis. We will focus our investigations on STING, a key node in the cytoplasmic nucleic acid sensing pathway. We will characterize a dozen diverse STING orthologs across Chiroptera to determine whether the same regulatory mechanisms exist across the order, or if multiple distinct regulatory mechanisms exist. We will narrow down the genetic determinants underlying these mechanisms by developing and applying “chimeric mutational scanning”, where we will create libraries of human-bat STING chimeras to identify the key residues that confer bat-specific regulation to signaling. In the second aim, we will shift our focus to identifying previously unappreciated immune genes and pathways present in bats. We will perform this with an unbiased transposon mutagenesis approach, which will be applied to cell lines from diverse bat species. Selection and sequencing of mutagenized bat cells resistant to the cytopathic effects of Vesicular Stomatitis Virus (VSV) replication, a proxy for rabies virus, will reveal innate immune genes that allow bats to survive infection. The mutagenized cells will also be exposed to VSV-EboGP (VSV pseudotyped with the Ebola virus glycoprotein), mimicking the mechanism used by Ebola virus to enter cells. Thus, with little extra effort, the same library will be used to identify bat innate immune genes that confer resistance to two zoonotic viruses thought to use bats as an animal reservoir. This work will both create the technologies needed to explore and understand the unknown aspects of bat immunity, and generate biological findings directly improving our understanding of bat innate immune mechanisms. These complementary approaches span a wide field of scope, from the functional interrogation of the importances of individual amino acids within known innate immune genes, to the whole genome level to highlight additional genes that should be the subject of focused investigation in the future.",,2024,Case Western Reserve University,181125,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21975,5U01AI151797-04,Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,"PROJECT SUMMARY/ABSTRACT Southeast Asia is one of the world’s highest-risk EID hotspots, the origin of the SARS pandemic, Nipah virus, and repeated outbreaks of influenza. This is driven by high diversity of wildlife and rapidly expanding demography that brings human and wildlife populations closer. This proposal will launch the Emerging Infectious Diseases - South East Asia Research Collaboration Hub (EID-SEARCH), a collaboration among leaders in emerging disease research in the USA, Thailand, Singapore and the 3 major Malaysian administrative regions. These researchers have networks that span >50 clinics, laboratories and research institutions across almost all SE Asian countries and will use the EID-SEARCH as an early warning system for outbreaks involving exchange of information, reagents, samples and technology, and a collaborative power- house for fundamental and translational research. The EID-SEARCH will also act as a significant asset to scale-up and deploy resources in the case of an outbreak in the region. This EIDRC will conduct research to: 1) Identify, characterize and rank spillover risk of high zoonotic potential viruses from wildlife, by analyzing previously-archived wildlife samples, conducting targeted wildlife surveillance, and using serology & PCR assays to identify novel viruses. These will be characterized to assess risk of spillover to people, and a series of in vitro (receptor binding, cell culture) and in vivo (humanized mouse and collaborative cross models) assays used to assess their potential to infect people and cause disease; 2) Collect samples and questionnaire data from human communities that live in EID hotspots and have high cultural and behavioral risk of animal exposure (e.g. wildlife hunting, bat guano collection). These will be tested with serological assays to identify evidence of novel virus spillover, and analyzed against metadata to identify key risk pathways for transmission; 3) Identify and characterize viral etiology of ‘cryptic’ outbreaks in clinical cohorts. We will conduct syndromic surveillance at clinics serving the populations in Aim 2, enroll patients with undiagnosed illness and symptoms consistent with emerging viral pathogens, and test samples with molecular and follow-up serological assays to identify causal links between these syndromes and novel viruses. This research will advance our understanding of the risk of novel viral emergence in a uniquely important region. It will also strengthen in-country research capacity by linking local infectious disease scientists with an international collaborative network that has proven capacity to conduct this work and produce significant findings. The large body of high impact collaborative research from this EIDRC leadership team provides proof-of-concept that EID-SEARCH has the background, collaborative network, experience, and skillset to act as a unique early warning system for novel EIDs of any etiology threatening to emerge in this hottest of the EID hotspots.",,2025,"ECOHEALTH ALLIANCE, INC.",1464739,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Immunity | Animal source and routes of transmission | Disease surveillance & mapping,2020 +P21976,5UM1AI148574-04,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,631871,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2020 +P21977,4R01AI160961-03,Engineering protease-resistant antiviral peptide inhibitors for SARS-CoV-2,"No vaccines or treatments for SARS-CoV-2 are yet available. A simple prophylactic antiviral strategy would protect naïve individuals from infection now. In the future, when vaccines should be available, a prophylactic antiviral will be essential for individuals who do not mount a suitable immune response. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viral diseases. The entry/fusion process for CoV (including SARS-CoV-2) is mediated by the viral envelope glycoprotein (S). Concerted action by the receptor-binding domain and the fusion domain is required for fusion. Upon viral attachment (and uptake in certain cases), large-scale conformational rearrangements occur in the fusion domain, driven by formation of a structure that couples protein refolding directly to membrane fusion. The formation of this structure can be targeted by fusion inhibitory peptides (C-terminal heptad repeat or HRC peptides) that prevent proper apposition of the HRC and HRN domains in S. We have found that conjugation of a lipid to an inhibitory peptide directs the peptide to cell membranes and increases antiviral efficacy. Analogous lipo-peptides prevent infection by several viruses (measles, Nipah, parainfluenza, influenza), and can be administered via the airway. Treatment is effective for some of these even several days after infection. In addition, we have shown that modifying the backbone of an HRC peptide via periodic replacement of α-amino acid residues with β- amino acid residues generates α/β-peptides that retain antiviral potency (toward HIV or parainfluenza) but are highly resistant to proteolysis. We recently generated an HRC lipopeptide that is effective against both SARS- CoV2 and MERS live viruses in vitro, blocks spread of SARS-CoV2 in human airway tissue, and inhibits transmission of SARS-CoV-2 between ferrets in direct contact. Here we propose to combine the lipid conjugation and backbone-modification strategies to generate potent inhibitors of SARS-CoV2 infection that display a long half-life in vivo. 1. Optimize the antiviral potency and bioavailability of SARS-CoV-2 HRC peptide fusion inhibitors via rational molecular engineering. Antiviral efficacy of α/β-lipopeptide candidates will be measured in quantitative in vitro assays, in authentic virus infection, and in a human airway model. 2. Evaluate the protection afforded by new backbone-modified α/β-lipopeptide fusion inhibitors against SARS-CoV-2 infection in hamsters. Analysis of in vivo biodistribution and toxicity of backbone modified S- CoV-2 α/β-lipopeptide fusion inhibitors and assessment of in vivo potency and resistance mechanisms will lay the foundation for a safe and effective SARS CoV-2 fusion inhibitor for coronavirus prevention and therapy.",,2026,Columbia University Health Sciences,718692,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21979,1R21AI169561-01A1,Functional genomic characterization of diverse bat innate immune mechanisms,"PROJECT SUMMARY Human health can be inextricably linked to our understanding of bats, as bats are known or predicted reservoirs for the precursors of many zoonotic viruses. Unfortunately, we still know little about bat immunology, and we do not know what characteristics allow them to survive with the same viruses that can readily kill other hosts such as humans. This problem is exacerbated by the fact that bats are an incredibly diverse order of mammals, so what we learn about the immunological mechanisms of one bat species may not be true for another. We need new techniques and technologies to efficiently explore the vast unknown universe of immunological mechanisms that exist across diverse bats. In this application, we propose to develop key tools needed to functionally characterize the genetic underpinnings of bat immunology. In the first aim, we propose to pair modern advances in recombinant DNA synthesis and cell engineering to more comprehensively investigate the function of orthologous genes already proposed to be important in bat immune homeostasis. We will focus our investigations on STING, a key node in the cytoplasmic nucleic acid sensing pathway. We will characterize a dozen diverse STING orthologs across Chiroptera to determine whether the same regulatory mechanisms exist across the order, or if multiple distinct regulatory mechanisms exist. We will narrow down the genetic determinants underlying these mechanisms by developing and applying “chimeric mutational scanning”, where we will create libraries of human-bat STING chimeras to identify the key residues that confer bat-specific regulation to signaling. In the second aim, we will shift our focus to identifying previously unappreciated immune genes and pathways present in bats. We will perform this with an unbiased transposon mutagenesis approach, which will be applied to cell lines from diverse bat species. Selection and sequencing of mutagenized bat cells resistant to the cytopathic effects of Vesicular Stomatitis Virus (VSV) replication, a proxy for rabies virus, will reveal innate immune genes that allow bats to survive infection. The mutagenized cells will also be exposed to VSV-EboGP (VSV pseudotyped with the Ebola virus glycoprotein), mimicking the mechanism used by Ebola virus to enter cells. Thus, with little extra effort, the same library will be used to identify bat innate immune genes that confer resistance to two zoonotic viruses thought to use bats as an animal reservoir. This work will both create the technologies needed to explore and understand the unknown aspects of bat immunity, and generate biological findings directly improving our understanding of bat innate immune mechanisms. These complementary approaches span a wide field of scope, from the functional interrogation of the importances of individual amino acids within known innate immune genes, to the whole genome level to highlight additional genes that should be the subject of focused investigation in the future.",,2024,Case Western Reserve University,241500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P21980,5R21AI169527-02,"Assessing the interferome in novel, purpose-driven bat-derived cells","Assessing the interferome of novel, purpose-driven bat-derived cells SUMMARY/ABSTRACT Over the last decade, bats have emerged as intriguing mammalian reservoirs of emerging high impact viruses that cause severe disease in humans and agricultural animals. However, bats that are naturally or experimentally infected with these viruses do not develop clinical signs of disease. Thus, understanding how bats tolerate virus infections may allow us to develop novel drugs or identify new drug targets for alternate mammalian species, such as humans. In spite of recent advances in bat immunology, studies have largely relied on cell culture models from selected bat species, limiting our understanding of this diverse mammalian order. The order Chiroptera is made up of over 1420 species of bats, and data from a handful of bats do not represent evolutionary adaptations in all bats. In addition, these reagents are not available on public repositories making it hard for the research community to pursue this intriguing and growing field of research. For our proposal, we propose to develop novel bat reagents, including primary and immortalized cells from five major bat species, Rousettus aegyptiacus, Pteropus alecto, Eptesicus fuscus, Artibeus jamaicensis, and Carollia perspicillata, representing bats that currently exist in research colonies, making future in vivo translational studies feasible and logical. Data from selected bats, such as Rousettus, Pteropus and Eptesicus bats suggest that bat cells have evolved adaptations in their cytokine responses to better tolerate virus infections relative to humans. Type I interferon (IFN) responses are the first line of mammalian antiviral defense, and although type I IFNs and their downstream effects have been studied in selected bat cells, global cellular responses and the full range of IFN-mediated antiviral effects or the ‘interferome’ remain elusive. For this project, we shall use our diverse bat cell types, derived from multiple bat species, to identify and delineate evolutionarily conserved and unique bat-specific IFN responses. Results from our study will shed light on intriguing questions around the ability of bats to control infection with zoonotic RNA viruses, along with making important discoveries on evolutionary adaptations in the mammalian type I IFN pathway. Importantly, our research will generate critical bat reagents, such as primary cells, cell lines, recombinant cytokines and molecular assays that will facilitate the development of larger collaborative projects to study bat immunology.",,2025,Washington State University,191789,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,,2022 +P21981,5U01AI151797-03,Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,"PROJECT SUMMARY/ABSTRACT Southeast Asia is one of the world’s highest-risk EID hotspots, the origin of the SARS pandemic, Nipah virus, and repeated outbreaks of influenza. This is driven by high diversity of wildlife and rapidly expanding demography that brings human and wildlife populations closer. This proposal will launch the Emerging Infectious Diseases - South East Asia Research Collaboration Hub (EID-SEARCH), a collaboration among leaders in emerging disease research in the USA, Thailand, Singapore and the 3 major Malaysian administrative regions. These researchers have networks that span >50 clinics, laboratories and research institutions across almost all SE Asian countries and will use the EID-SEARCH as an early warning system for outbreaks involving exchange of information, reagents, samples and technology, and a collaborative power- house for fundamental and translational research. The EID-SEARCH will also act as a significant asset to scale-up and deploy resources in the case of an outbreak in the region. This EIDRC will conduct research to: 1) Identify, characterize and rank spillover risk of high zoonotic potential viruses from wildlife, by analyzing previously-archived wildlife samples, conducting targeted wildlife surveillance, and using serology & PCR assays to identify novel viruses. These will be characterized to assess risk of spillover to people, and a series of in vitro (receptor binding, cell culture) and in vivo (humanized mouse and collaborative cross models) assays used to assess their potential to infect people and cause disease; 2) Collect samples and questionnaire data from human communities that live in EID hotspots and have high cultural and behavioral risk of animal exposure (e.g. wildlife hunting, bat guano collection). These will be tested with serological assays to identify evidence of novel virus spillover, and analyzed against metadata to identify key risk pathways for transmission; 3) Identify and characterize viral etiology of ‘cryptic’ outbreaks in clinical cohorts. We will conduct syndromic surveillance at clinics serving the populations in Aim 2, enroll patients with undiagnosed illness and symptoms consistent with emerging viral pathogens, and test samples with molecular and follow-up serological assays to identify causal links between these syndromes and novel viruses. This research will advance our understanding of the risk of novel viral emergence in a uniquely important region. It will also strengthen in-country research capacity by linking local infectious disease scientists with an international collaborative network that has proven capacity to conduct this work and produce significant findings. The large body of high impact collaborative research from this EIDRC leadership team provides proof-of-concept that EID-SEARCH has the background, collaborative network, experience, and skillset to act as a unique early warning system for novel EIDs of any etiology threatening to emerge in this hottest of the EID hotspots.",,2025,"ECOHEALTH ALLIANCE, INC.",1504400,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Immunity | Animal source and routes of transmission | Disease surveillance & mapping,2020 +P21982,75N93019D00002-0-759302200001-1,Task B08: Production of Well Characterized Challenge Material (WCCM) for BSL-3/BSL-4 Viral Pathogens.,"This contract provides in vitro testing of potential anti-viral agents, maintenance of viral stocks and cell lines needed to grow the viruses, and development of related assays.",,2022,AMERICAN TYPE CULTURE COLLECTION,429866,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P21983,5UM1AI148574-03,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,638651,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2020 +P21984,3UM1AI148574-03S1,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2023,New York University School Of Medicine,543651,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2021 +P21985,3UM1AI148574-03S2,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,375787,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Not applicable,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2021 +P21986,5R01AI160961-02,Engineering protease-resistant antiviral peptide inhibitors for SARS-CoV-2,"No vaccines or treatments for SARS-CoV-2 are yet available. A simple prophylactic antiviral strategy would protect naïve individuals from infection now. In the future, when vaccines should be available, a prophylactic antiviral will be essential for individuals who do not mount a suitable immune response. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viral diseases. The entry/fusion process for CoV (including SARS-CoV-2) is mediated by the viral envelope glycoprotein (S). Concerted action by the receptor-binding domain and the fusion domain is required for fusion. Upon viral attachment (and uptake in certain cases), large-scale conformational rearrangements occur in the fusion domain, driven by formation of a structure that couples protein refolding directly to membrane fusion. The formation of this structure can be targeted by fusion inhibitory peptides (C-terminal heptad repeat or HRC peptides) that prevent proper apposition of the HRC and HRN domains in S. We have found that conjugation of a lipid to an inhibitory peptide directs the peptide to cell membranes and increases antiviral efficacy. Analogous lipo-peptides prevent infection by several viruses (measles, Nipah, parainfluenza, influenza), and can be administered via the airway. Treatment is effective for some of these even several days after infection. In addition, we have shown that modifying the backbone of an HRC peptide via periodic replacement of α-amino acid residues with β- amino acid residues generates α/β-peptides that retain antiviral potency (toward HIV or parainfluenza) but are highly resistant to proteolysis. We recently generated an HRC lipopeptide that is effective against both SARS- CoV2 and MERS live viruses in vitro, blocks spread of SARS-CoV2 in human airway tissue, and inhibits transmission of SARS-CoV-2 between ferrets in direct contact. Here we propose to combine the lipid conjugation and backbone-modification strategies to generate potent inhibitors of SARS-CoV2 infection that display a long half-life in vivo. 1. Optimize the antiviral potency and bioavailability of SARS-CoV-2 HRC peptide fusion inhibitors via rational molecular engineering. Antiviral efficacy of α/β-lipopeptide candidates will be measured in quantitative in vitro assays, in authentic virus infection, and in a human airway model. 2. Evaluate the protection afforded by new backbone-modified α/β-lipopeptide fusion inhibitors against SARS-CoV-2 infection in hamsters. Analysis of in vivo biodistribution and toxicity of backbone modified S- CoV-2 α/β-lipopeptide fusion inhibitors and assessment of in vivo potency and resistance mechanisms will lay the foundation for a safe and effective SARS CoV-2 fusion inhibitor for coronavirus prevention and therapy.",,2023,Columbia University Health Sciences,722958,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P21989,5U01AI151797-02,Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,"PROJECT SUMMARY/ABSTRACT Southeast Asia is one of the world’s highest-risk EID hotspots, the origin of the SARS pandemic, Nipah virus, and repeated outbreaks of influenza. This is driven by high diversity of wildlife and rapidly expanding demography that brings human and wildlife populations closer. This proposal will launch the Emerging Infectious Diseases - South East Asia Research Collaboration Hub (EID-SEARCH), a collaboration among leaders in emerging disease research in the USA, Thailand, Singapore and the 3 major Malaysian administrative regions. These researchers have networks that span >50 clinics, laboratories and research institutions across almost all SE Asian countries and will use the EID-SEARCH as an early warning system for outbreaks involving exchange of information, reagents, samples and technology, and a collaborative power- house for fundamental and translational research. The EID-SEARCH will also act as a significant asset to scale-up and deploy resources in the case of an outbreak in the region. This EIDRC will conduct research to: 1) Identify, characterize and rank spillover risk of high zoonotic potential viruses from wildlife, by analyzing previously-archived wildlife samples, conducting targeted wildlife surveillance, and using serology & PCR assays to identify novel viruses. These will be characterized to assess risk of spillover to people, and a series of in vitro (receptor binding, cell culture) and in vivo (humanized mouse and collaborative cross models) assays used to assess their potential to infect people and cause disease; 2) Collect samples and questionnaire data from human communities that live in EID hotspots and have high cultural and behavioral risk of animal exposure (e.g. wildlife hunting, bat guano collection). These will be tested with serological assays to identify evidence of novel virus spillover, and analyzed against metadata to identify key risk pathways for transmission; 3) Identify and characterize viral etiology of ‘cryptic’ outbreaks in clinical cohorts. We will conduct syndromic surveillance at clinics serving the populations in Aim 2, enroll patients with undiagnosed illness and symptoms consistent with emerging viral pathogens, and test samples with molecular and follow-up serological assays to identify causal links between these syndromes and novel viruses. This research will advance our understanding of the risk of novel viral emergence in a uniquely important region. It will also strengthen in-country research capacity by linking local infectious disease scientists with an international collaborative network that has proven capacity to conduct this work and produce significant findings. The large body of high impact collaborative research from this EIDRC leadership team provides proof-of-concept that EID-SEARCH has the background, collaborative network, experience, and skillset to act as a unique early warning system for novel EIDs of any etiology threatening to emerge in this hottest of the EID hotspots.",,2025,"ECOHEALTH ALLIANCE, INC.",1505568,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Immunity | Animal source and routes of transmission | Disease surveillance & mapping,2020 +P21991,1U01GH002332-01,"RFA-GH-21-006, Establishing the Southeast Asia Serological Surveillance Network (SASSNet) for Emergent, Endemic, and Vaccine-Preventable Infections","Project Summary The project aims to establish the Southeast Asian Serological Surveillance Network (SASSNet) and operations in Indonesia and Viet Nam. The Network will apply optimized and validated serological sampling, analysis, and reporting of exposures to emerging and endemic neglected tropical infectious diseases of regional importance. The project leverages both robotic ELISA and Luminex multiplex high throughput platforms in order to efficiently and sustainably surveil several dozen infections/vaccinations. Sampling strategy is the pragmatic approach of age-stratified anonymized residual blood specimens from networks of 25 hospitals in Indonesia and 20 in Viet Nam. The project joins academic research partners from the University of Oxford’s clinical research units in Indonesia and Viet Nam with researchers within the respective Ministry of Health in both nations. The first year of effort focuses exclusively on serological surveillance of SARS-CoV-2 through 3 distinct workstreams: 1) establishing routine national serological surveillance by ELISA; 2) cross-sectional surveys for exposure to SARS-CoV at selected sites; and 3) following two longitudinal cohorts for serological assessment by ELISA over a 1-year period, where enrollment in one cohort immediately follows qPCR positivity for SARS-CoV-2, and in the other immediately follows vaccination against COVID-19. Year 1 will also see the optimizing and validation of a multiplex Luminex assay for six distinct SARS-CoV-2 antigenic targets and three distinct immunoglobulins (A, M, and G), along with Spike S1 and Spike N proteins of MERS-CoV, and four seasonal coronaviruses. The same multiplex assay will later include eight emerging infections (e.g. Nipah, Zika, and Japanese encephalitis viruses), neglected tropical infections (e.g., Dengue, malaria, filariasis, leprosy, and intestinal helminthiases), and vaccine-preventable infections (e.g. measles, diphtheria, and tetanus). That multiplex serological assay will constitute the basis of routine national serological surveillance, and the project aims to build that capacity within Ministry of Health facilities in Indonesia and Viet Nam, and to turn those facilities over to the respective authorities at the end of the 5- year life of the project.",,2023,University Of Oxford,649989,Human Populations | Viruses,Asian | Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus | Flaviviridae | Paramyxovirdiae,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Zika virus disease | Nipah and henipaviral disease | Other,National Institutes of Health (NIH),United States of America,Americas,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Immunity | Disease susceptibility | Disease surveillance & mapping,2022 +P21992,3UM1AI148574-02S3,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2022,New York University School Of Medicine,6820430,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2021 +P21993,5UM1AI148574-02,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,655601,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2020 +P21995,1U01AI151797-01,Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,"PROJECT SUMMARY/ABSTRACT Southeast Asia is one of the world’s highest-risk EID hotspots, the origin of the SARS pandemic, Nipah virus, and repeated outbreaks of influenza. This is driven by high diversity of wildlife and rapidly expanding demography that brings human and wildlife populations closer. This proposal will launch the Emerging Infectious Diseases - South East Asia Research Collaboration Hub (EID-SEARCH), a collaboration among leaders in emerging disease research in the USA, Thailand, Singapore and the 3 major Malaysian administrative regions. These researchers have networks that span >50 clinics, laboratories and research institutions across almost all SE Asian countries and will use the EID-SEARCH as an early warning system for outbreaks involving exchange of information, reagents, samples and technology, and a collaborative power- house for fundamental and translational research. The EID-SEARCH will also act as a significant asset to scale-up and deploy resources in the case of an outbreak in the region. This EIDRC will conduct research to: 1) Identify, characterize and rank spillover risk of high zoonotic potential viruses from wildlife, by analyzing previously-archived wildlife samples, conducting targeted wildlife surveillance, and using serology & PCR assays to identify novel viruses. These will be characterized to assess risk of spillover to people, and a series of in vitro (receptor binding, cell culture) and in vivo (humanized mouse and collaborative cross models) assays used to assess their potential to infect people and cause disease; 2) Collect samples and questionnaire data from human communities that live in EID hotspots and have high cultural and behavioral risk of animal exposure (e.g. wildlife hunting, bat guano collection). These will be tested with serological assays to identify evidence of novel virus spillover, and analyzed against metadata to identify key risk pathways for transmission; 3) Identify and characterize viral etiology of ‘cryptic’ outbreaks in clinical cohorts. We will conduct syndromic surveillance at clinics serving the populations in Aim 2, enroll patients with undiagnosed illness and symptoms consistent with emerging viral pathogens, and test samples with molecular and follow-up serological assays to identify causal links between these syndromes and novel viruses. This research will advance our understanding of the risk of novel viral emergence in a uniquely important region. It will also strengthen in-country research capacity by linking local infectious disease scientists with an international collaborative network that has proven capacity to conduct this work and produce significant findings. The large body of high impact collaborative research from this EIDRC leadership team provides proof-of-concept that EID-SEARCH has the background, collaborative network, experience, and skillset to act as a unique early warning system for novel EIDs of any etiology threatening to emerge in this hottest of the EID hotspots.",,2025,"ECOHEALTH ALLIANCE, INC.",1546744,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Immunity | Animal source and routes of transmission | Disease surveillance & mapping,2020 +P21997,1UM1AI148574-01,Establishment of the New York University Vaccine and Treatment Evaluation Unit (NYU VTEU),"PROJECT SUMMARY Establishment of New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) is proposed in response to RFA-AI-18-046 entitled “Vaccine and Treatment Evaluation Units (VTEUs) (UM1 Clinical Trial Required)”. NYU VTEU will be one of the 10 fixed sites that will participate in the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). Within the consortium, this NYU VTEU will work closely with NIAID, the Leadership Group (LG), other VTEUs, and NIAID-supported research resources. The broad, long-term objective of NYU VTEU is to protect and restore human health through clinical trials of innovative medical countermeasures to combat microbial threats. While major advances in vaccines and antimicrobial agents have resulted in large reductions in morbidity and mortality, emerging and re-emerging viral threats (e.g., Ebola, Zika, SARS, MERS, Nipah, dengue) and widespread antimicrobial drug resistance threaten to reverse these gains. Furthermore, we remain without broadly effective vaccines against the major infectious disease killers: tuberculosis, malaria, and AIDS. A better seasonal influenza vaccine and ultimately a universal influenza vaccine are needed, as evidenced by 80,000 US flu deaths during the 2017-18 season. Working with NIAID and LG, NYU VTEU will review, refine and implement the infectious diseases clinical research agenda. As per RFA-AI-18-046, the initial IDCRC priority research areas include: sexually transmitted infections (STIs), malaria and neglected tropical diseases, respiratory infections, enteric diseases, and emerging infections. The medical countermeasures to be studied include: vaccines, biologics, therapeutics, biomarkers with predictive value, devices, and diagnostics. NYU VTEU team has extensive expertise and experience with these priority infectious diseases and countermeasures. When high priority pathogens need to be addressed quickly, NYU VTEU has demonstrated experience in rapid responsiveness and surge capacity - critical elements of the optimal VTEU. Importantly, in order to speed the development of needed vaccines, an inpatient research unit for controlled human infection model (CHIM) studies has been developed at NYU VTEU. NYU School of Medicine comprises seven major hospitals. The diverse patients cared for in these hospitals and associated clinics (8.4 million outpatient visits and 144,000 inpatient admissions in 2018), along with the large diverse NYC population of 8.6 million (largest city in US), are ideal for recruitment of patients with specific conditions and healthy individuals.",,2026,New York University School Of Medicine,451484,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure | Medicines, vaccines & other technologies",2020 +P21998,75N93021C00021-P00003-9999-1,Development of Therapeutic Products for Marburg Virus,"To support the advanced development of a promising candidate therapeutic for NIAID Category A, B, and C Priority Pathogens or emerging infectious diseases. The research and development activities to be supported will allow the candidate therapeutic product to progress through the product development pathway, and include preclinical and IND enabling development activities, chemistry optimization/development, GMP manufacturing, and clinical safety and efficacy assessment.",,2025,"ABVACC, INC.",1696004,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies | Clinical trial (unspecified trial phase),2021 +P22000,1R01GM150502-01,The biochemical mechanism and pharmacological inhibition of phosphatidylinositol phosphate kinases,"Project Summary / Abstract The objective of the proposed research is to elucidate the biochemical mechanisms underlying the exquisite substrate binding and catalytic specificity of two phosphatidylinositol phosphate 5-kinases (PIP5K, PIKfyve). The PIPK family of lipid kinases include PIP5K (type 1), PIP4K (type 2) and PIKfyve (type 3), and is primarily responsible for converting phosphatidylinositol monophosphate lipids into PI(4,5)P2 and PI(3,5)P2. Despite sequence homology, these kinases are highly selective in substrate binding [PIP5K binds PI(4)P, PIP4K binds PI(5)P, and PIKfyve binds PI(3)P] and in catalytic activity [PIP5K and PIKfyve phosphorylate the C5 hydroxyl of the lipid's inositol head group, whereas PIP4K phosphorylates the C4 hydroxyl]. We and others have previously identified two structural elements within the kinase domain, the specificity loop and a conserved PIP-binding motif, that contribute to substrate selectivity, but how these two elements cooperate to confer kinase specificity remains undefined at the structural level. In aim 1, we plan crosslinking strategies to stabilize the specificity loop to facilitate co-crystallization with lipid substrates. We also plan to generate and crystallize a minimalistic catalytic core domain of PIKfyve. In aim 2, we propose genetic and chemical biological experiments to examine the role of PIKfyve in the life cycle of SARS-CoV-2. Several large-scale drug repurposing programs have identified apilimod, a PIKfyve inhibitor, as a top lead in suppressing SARS-CoV-2 replication in cell culture (a phase II clinical trial of apilimod in treating COVID-19 is ongoing at the Yale Center for Clinical Investigation). This discovery, together with earlier observations that apilimod also reduces infection by Ebola and Marburg viruses, has generated great interest in pharmacologically targeting PIKfyve. Drawing on structural and biochemical knowledge about the lipid kinase family, as well as chemical tools previously developed to target PIP4K, we have discovered a new class of potent PIKfyve inhibitors and plan to use them together with apilimod to interrogate how PIKfyve inhibition disrupts SARS-CoV-2 infection. All previously known PIKfyve inhibitors are structurally related to apilimod, and their binding mode to the lipid kinase is unknown. The new inhibitor class is significant because it not only adds confidence to the proposed involvement of PIKfyve in SARS-CoV-2 infection, but also has a known binding mode to PIPK, which should facilitate future optimization by medicinal chemistry.",,2027,Yale University,321957,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease | Marburg virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2023 +P22003,5R24GM136766-03,A Biomedical Mass Spectrometry Resource: Ongoing Driving Biomedical Projects,"Project Summary The Washington University NIGMS Biomedical Resource seeks to continue its successful collaborative work with biomedical researchers engaged in understanding disease and maintaining human health. This Resource supports a wide array of scientists requiring structural proteomics and complex lipidomics by expertly using mass spectrometry tools, many of which were developed at this Resource over the last 15 years. The dedicated scientists at the Resource have more than a century of combined experience and continue to collaborate with investigators working on important biomedical problems including viral pathogens like Ebola, Dengue, Zika, and Marburg, bacterial pathogens such as the causative agents of tuberculosis and leishmania, plasmodia that cause malaria, Alzheimer's and Parkinson's diseases, diabetes, metabolic syndrome, urinary tract infections, and cancer. Resource staff investigators, motivated by national and international collaborators in academic, industrial, and governmental laboratories, provide support for the study of cellular calcium regulation, lipid metabolism, antibody-antigen binding, and many other problems in structural and functional biology. In addition, the dedicated scientists at this Resource will support successful dissemination, training, and outreach to the scientific and broader communities. This grant will allow them to continue the application of mass spectrometry to these problems as they transition to other sources of support that allow them to honor commitments to their large and diverse group of collaborators.",,2024,Washington University,659894,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",,2020 +P22005,272201800013I-0-759302200003-1,TASK V14: CREATION OF A MARBURGVIRUS INTERNATIONAL STANDARD,The Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases contract provides a variety of product development services from early feasibility studies through activities required for the submission of Biologic License Application (BLA) and/or Investigational New Drug (IND) applications. These services will facilitate the development and introduction of new vaccine candidates and biologics (regulated by CBER) against potential agents of bioterrorism and emerging and re-emerging infectious diseases.,,2024,BATTELLE CENTERS/PUB HLTH RES & EVALUATN,656189,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22006,272201800013I-P00001-759302100002-1,Task V11: General Safety Toxicity Testing,The Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases contract provides a variety of product development services from early feasibility studies through activities required for the submission of Biologic License Application (BLA) and/or Investigational New Drug (IND) applications. These services will facilitate the development and introduction of new vaccine candidates and biologics (regulated by CBER) against potential agents of bioterrorism and emerging and re-emerging infectious diseases.,,2024,BATTELLE CENTERS/PUB HLTH RES & EVALUATN,151942,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Health Systems Research","Pre-clinical studies | Pre-clinical studies | Medicines, vaccines & other technologies",2021 +P22008,5R03AI156591-02,Human TfR1-expressing hamsters to model New World arenaviral hemorrhagic fever,"PROJECT SUMMARY Mammarenaviruses are endemic in rodent populations worldwide and their zoonotic transmission can lead to a severe life-threatening hemorrhagic fever (HF) syndrome. In the Americas, five New World mammarenaviruses (NWAs) are known to cause HF. In the absence of FDA-licensed vaccines or antiviral therapies, these viruses pose a significant public health risk and a threat to national security. Research to understand NWA pathogenesis and develop effective countermeasures is severely limited by the lack of small-animal models that faithfully mirror human disease. We recently demonstrated that transgenic expression of human transferrin receptor 1 (huTfR1), the known cellular receptor used by the pathogenic NWAs, confers susceptibility in mice to lethal disease following challenge with the Junin arenavirus (JUNV), the agent of Argentine HF. However, the mice do not manifest signs of hemorrhagic disease that are prominent features of severe cases of NWA HF in humans. We and others have shown that golden Syrian hamsters infected with related nonpathogenic NWAs that do not use huTfR1 develop a severe HF-like syndrome with many of the cardinal features of hemorrhagic disease, including coagulopathy, extensive petechia, bleeding from the oronasal mucosal region and vascular leak. Moreover, we recently showed that expression of huTfR1 in hamster cell lines significantly augments JUNV infection. Thus, we hypothesize that hamsters engineered to express huTfR1 will be susceptible to JUNV infection, resulting in a HF-like syndrome more representative of human disease. To explore this hypothesis, we will pursue the following Specific Aims: Aim 1. Develop a huTfR1 knock-in (KI) golden Syrian hamster line. We will design and test single guide (sg)RNAs targeting the 3’ end of the hamster TfR1 gene for insertion of the huTfR1 open reading frame. By appending the huTfR1 cDNA via a T2A peptide linker immediately before the stop codon of the hamster TfR1 gene, we will ensure expression of huTfR1 at physiological levels and with normal tissue distribution. The huTfR1 hamster line will be generated by a well-established pronuclear injection procedure with the Cas9/sgRNA ribonucleoprotein complex and the huTfR1 cDNA donor construct. Aim 2. Evaluate the susceptibility of the huTfR1 hamster to JUNV infection. Wild-type and huTfR1 KI hamsters will be challenged with JUNV to assess differences in viral replication and development of disease. We anticipate that expression of huTfR1 will boost viral replication leading to a HF-like syndrome in the hamsters. Disease parameters evaluated daily will include body weight, temperature and clinical disease signs including petechia and mucosal bleeding. Viral loads will be determined from blood samples taken one week after JUNV challenge, a point at which huTfR1 hamsters are expected to develop signs of disease and have measurable viremia. The ultimate goal of this project is to produce a novel hamster model of NWA HF to support development of host-directed therapies that would complement direct-acting antivirals to improve outcomes in patients suffering from severe disease caused by pathogenic NWAs.",,2024,Utah State University,73000,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +P22009,75N93021C00021-0-9999-1,Development of Therapeutic Products for Marburg Virus,"To support the advanced development of a promising candidate therapeutic for NIAID Category A, B, and C Priority Pathogens or emerging infectious diseases. The research and development activities to be supported will allow the candidate therapeutic product to progress through the product development pathway, and include preclinical and IND enabling development activities, chemistry optimization/development, GMP manufacturing, and clinical safety and efficacy assessment.",,2025,"INTEGRATED BIOTHERAPEUTICS, INC.",1749368,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Filoviridae,,,,,,,,,Marburg virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies | Clinical trial (unspecified trial phase),2021 +P22010,5R24GM136766-02,A Biomedical Mass Spectrometry Resource: Ongoing Driving Biomedical Projects,"Project Summary The Washington University NIGMS Biomedical Resource seeks to continue its successful collaborative work with biomedical researchers engaged in understanding disease and maintaining human health. This Resource supports a wide array of scientists requiring structural proteomics and complex lipidomics by expertly using mass spectrometry tools, many of which were developed at this Resource over the last 15 years. The dedicated scientists at the Resource have more than a century of combined experience and continue to collaborate with investigators working on important biomedical problems including viral pathogens like Ebola, Dengue, Zika, and Marburg, bacterial pathogens such as the causative agents of tuberculosis and leishmania, plasmodia that cause malaria, Alzheimer's and Parkinson's diseases, diabetes, metabolic syndrome, urinary tract infections, and cancer. Resource staff investigators, motivated by national and international collaborators in academic, industrial, and governmental laboratories, provide support for the study of cellular calcium regulation, lipid metabolism, antibody-antigen binding, and many other problems in structural and functional biology. In addition, the dedicated scientists at this Resource will support successful dissemination, training, and outreach to the scientific and broader communities. This grant will allow them to continue the application of mass spectrometry to these problems as they transition to other sources of support that allow them to honor commitments to their large and diverse group of collaborators.",,2023,Washington University,776346,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",,2020 +P22012,5R21AI153480-02,Broad Spectrum Anti-viral Compounds Targeting the SKI Complex,"Project Summary The RNA Exosome and SKI complex are major cellular machines that degrade host RNA. This machine is required for several reasons in the cell including maintenance of current RNA levels and to reduce the level of cytoplasmic RNA such that the RIGI and MDA5 sensors can detect viral RNA other than host RNA. The SKI complex was identified in a genetic screen as a host protein that interacts with both Influenza NS1 and MERS-CoV ORF4a. We were able to demonstrate that knocking down these proteins in cells caused a reduction in viral replication and an increase in Interferon stimulated gene induction, irrespective of whether a virus was there or not. The SKI complex in yeast has been crystalized and upon modeling of the human structure, we in silico identified compounds that could potentially bind to a member of the complex, WDR61. In cell culture experiments, we identified 4 compounds from the 40 identified in the modeling, that block Influenza virus, MERS-CoV and SARS-CoV replication. In this proposal, we will determine the mechanism of action of the compounds and NS1 and ORF4a on the SKI complex. We will also initiate in vivo studies to evaluate the antiviral effectiveness of the SKI targeted plasmids on Influenza virus and MERS-CoV mouse models. This work will validate a novel host target and compounds directed at the SKI complex as broadly acting antivirals.",,2023,University Of Maryland Baltimore,193125,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22014,1R24GM136766-01,A Biomedical Mass Spectrometry Resource: Ongoing Driving Biomedical Projects,"Project Summary The Washington University NIGMS Biomedical Resource seeks to continue its successful collaborative work with biomedical researchers engaged in understanding disease and maintaining human health. This Resource supports a wide array of scientists requiring structural proteomics and complex lipidomics by expertly using mass spectrometry tools, many of which were developed at this Resource over the last 15 years. The dedicated scientists at the Resource have more than a century of combined experience and continue to collaborate with investigators working on important biomedical problems including viral pathogens like Ebola, Dengue, Zika, and Marburg, bacterial pathogens such as the causative agents of tuberculosis and leishmania, plasmodia that cause malaria, Alzheimer's and Parkinson's diseases, diabetes, metabolic syndrome, urinary tract infections, and cancer. Resource staff investigators, motivated by national and international collaborators in academic, industrial, and governmental laboratories, provide support for the study of cellular calcium regulation, lipid metabolism, antibody-antigen binding, and many other problems in structural and functional biology. In addition, the dedicated scientists at this Resource will support successful dissemination, training, and outreach to the scientific and broader communities. This grant will allow them to continue the application of mass spectrometry to these problems as they transition to other sources of support that allow them to honor commitments to their large and diverse group of collaborators.",,2023,Washington University,912639,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Filoviridae | Flaviviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",,2020 +P22016,3UM1AI068632-14S2,LOC-IMPAACT Leadership GroupPharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the US,"PROJECT SUMMARY Remdesivir, the first drug with preliminary evidence of efficacy for treatment of COVID-19, has recently been awarded Emergency Use Authorization from the FDA for use in hospitalized patients with documented COVID- 19. There are no documented pharmacokinetic (PK) and limited safety data available regarding use in pregnancy. The physiological changes associated with pregnancy can have a dramatic impact on drug disposition, and use of therapeutic agents during pregnancy poses unique safety concerns. The aims of the proposed Phase IV prospective, open label, non-randomized study are to evaluate the PK (Specific Aim 1) and safety (Specific Aim 2) of remdesivir provided through a compassionate use program or open access protocol in 20 hospitalized pregnant women for treatment of symptoms related to COVID-19, using a well-established study approach and leveraging the extensive infrastructure of the NIH-sponsored International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and in collaboration with Gilead Sciences. The study will be conducted at multiple experienced IMPAACT-affiliated sites in the US with proven access to the study population. Hospitalized pregnant women >18 years of age with COVID-19 scheduled to receive remdesivir as part of clinical care will be eligible for enrollment if willing and able to provide informed consent or if a legally recognized representative can do so on her behalf. The primary outcome measure will be a comparison of remdesivir PK parameters from study participants (pregnant women) with those in non-pregnant adults. The primary PK endpoints are remdesivir and its major metabolite, GS-441524, AUC0-24h at Day 1, and GS-441524 AUCtau after last dose. Intensive and sparse sampling remdesivir concentrations will be used in a population PK analysis to assess the impact of covariates such as stage of pregnancy and severity of COVID- 19 disease on remdesivir PK parameters. Plasma remdesivir and GS-441524 concentrations will be quantified in the laboratory being used for ongoing Gilead-supported studies of remdesivir in non-pregnant adults, ensuring comparability. At entry and after the last dose, safety monitoring will include liver and renal function tests and complete blood count (if not obtained within 24 hours for clinical care) and medical record abstraction for other laboratory test results and clinical events. Medical record abstraction for laboratory test results and clinical events will also be performed at 4 weeks postdosing and after labor and delivery. The proposed study will provide urgently needed pregnancy-specific clinical pharmacology data that will ensure that remdesivir can be used safely and effectively in pregnant women as rapidly as possible. This research could also serve as a model to rapidly provide pregnancy PK and safety data for other COVID- therapeutics as they become available.",,2022,Johns Hopkins University,942554,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P22017,1R21AI153480-01,Broad Spectrum Anti-viral Compounds Targeting the SKI Complex,"Project Summary The RNA Exosome and SKI complex are major cellular machines that degrade host RNA. This machine is required for several reasons in the cell including maintenance of current RNA levels and to reduce the level of cytoplasmic RNA such that the RIGI and MDA5 sensors can detect viral RNA other than host RNA. The SKI complex was identified in a genetic screen as a host protein that interacts with both Influenza NS1 and MERS-CoV ORF4a. We were able to demonstrate that knocking down these proteins in cells caused a reduction in viral replication and an increase in Interferon stimulated gene induction, irrespective of whether a virus was there or not. The SKI complex in yeast has been crystalized and upon modeling of the human structure, we in silico identified compounds that could potentially bind to a member of the complex, WDR61. In cell culture experiments, we identified 4 compounds from the 40 identified in the modeling, that block Influenza virus, MERS-CoV and SARS-CoV replication. In this proposal, we will determine the mechanism of action of the compounds and NS1 and ORF4a on the SKI complex. We will also initiate in vivo studies to evaluate the antiviral effectiveness of the SKI targeted plasmids on Influenza virus and MERS-CoV mouse models. This work will validate a novel host target and compounds directed at the SKI complex as broadly acting antivirals.",,2022,University Of Maryland Baltimore,231750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22018,1R01AI176505-01A1,Mechanisms of tunneling nanotube formation by ZIKV NS1 in viral host interactions at the maternal-fetal interface,"PROJECT SUMMARY Although primarily transmitted by mosquitoes, the Zika virus (ZIKV) has the unique ability among flaviviruses to be transmitted horizontally through sexual contact, or vertically from mother to fetus. The vertical mode of transmission has led to devastating pregnancy and fetal development outcomes that came to light in 2015-16, as a ZIKV epidemic emerged in the Western hemisphere and a public health emergency of international concern was declared. The threat of future ZIKV epidemics persists and many nations where it has become endemic continue to struggle with the adverse effects of infection. Meanwhile, scientists have struggled to understand the mechanisms that underlie maternal-fetal transmission of ZIKV on a cellular and molecular level. This proposal presents preliminary data for the first time that supports a novel hypothesis that transmission of ZIKV at the maternal-fetal interface is facilitated by the formation of tunneling nanotubes (TNTs), which are actin-based intercellular transport conduits that have been shown to play a role in the spread of other viruses. Among other things, the preliminary data indicates that, 1) ZIKV infection induces the formation of TNTs in various cell types, including human placental trophoblast cells, 2) the ZIKV non-structural protein 1 (NS1) is alone sufficient to induce TNT formation, whereas NS1 proteins of several other flaviviruses tested do not appear to have this ability, with the exception of WNV to a small degree, and 3) ZIKV-induced TNTs transport mitochondria in trophoblast cells in a manner that may be exploited for the benefit of virus propagation and transmission. Building on these observations, and using the tools the PIs have so far developed, they propose a formal collaboration and rigorous set of experiments designed to test this hypothesis. First, using a library of labeled ZIKV constructs, confocal imaging, and an advanced affinity purification-mass spectrometry approach, the role of NS1 in inducing TNT formation without affecting virus replication and assembly will be established in human trophoblast cells; then specific regions of this protein will be identified that may participate in signaling or interaction with host proteins; and the question of whether TNTs transport ZIKV RNA and/or whole virions will be evaluated. Second, mouse models of ZIKV infection during pregnancy that the PIs have developed in prior work will be used to investigate the role of TNT formation in ZIKV pathogenesis and vertical transmission; the impact of TNT formation on ZIKV infection pathogenesis in the placenta will be evaluated; and spatial transcriptomics paired with tissue profiling will be used to identify genomic pathways in the placenta that are key for TNT formation. And thirdly, the nature of mitochondria transport via TNTs will be investigated to determine the role of any interactions with ZIKV virions or NS1, and the effects this has on cell metabolism and viral transmission. If successful, the resulting findings will establish an important and undescribed cellular pathway for transmission of the ZIKV that will serve as a likely target for future therapeutic interventions aimed at preventing microcephaly and other effects of ZIKV infection during pregnancy.",,2028,"PENNSYLVANIA STATE UNIVERSITY, THE",716381,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2023 +P22019,5R01AI148264-05,Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates,"Abstract Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that recently caused an outbreak in the Americas. The establishment of ZIKV transmission cycle in tropical/sub-tropical regions that are endemic to other close-related flaviviruses such as Dengue virus (DENV) has raised concerns, mainly by their cross-immunological interactions and the implications of this for development of severe clinical manifestations. Several groups have demonstrated that DENV-immune serum from humans can enhance ZIKV infection in vitro and in vivo in an immunodeficient mice model. This phenomenon known as Antibody Dependent-Enhancement (ADE) has been linked to severe dengue clinical manifestations. Little is known about the effect of a previous immunity to ZIKV on a subsequent DENV infection. It is highly necessary to characterize correlates of protection in the control of a heterologous secondary DENV or ZIKV infection in the presence of previous DENV or ZIKV immunity in an immunological competent animal model that resemble the human immune system like the Non- Human Primates. Our group have preliminary data showing a potential protective role of the cellular immune response in dengue- immune or ZIKV-immune subjects during a heterologous secondary infection with ZIKV or dengue. The overall hypothesis behind this work is that the cross-primed cellular immune response may be critical controlling the DENV and ZIKV infection and provides heterologous protection against each other. To test this hypothesis, we propose a series of straightforward experiments by depleting the CD4+ or CD8+ or CD20+ cells at different time points before a primary or a secondary infection with dengue or ZIKV. This type of experiment has not been performed before in NHP. For these experiments we will use rhesus macaques bred and housed at the Caribbean Primate Research Center that has proven to be the purer Indian-origin macaque population of all populations in the USA or imported animals, without having a significant level of inbreeding. For first time in any study in the flavivirus field, we will use a large data on the MHC typing of this population to characterize specific CD4 and/or CD8 T cells epitopes playing a role in the T cells immune response against dengue and ZIKV. Understanding correlates of protection between ZIKV and DENV is essential to anticipate the outcome of the secondary infection, the design of diagnostics methods and more relevant, to support the design of highly effective ZIKV and DENV vaccines in the scenario of previous DENV or ZIKV immunity, respectively. Undoubtedly, NHP provide us with a unique immunological tool very close to the human system to provide the answers to the questions we are outlying on this application.",,2024,UNIVERSITY OF PUERTO RICO MED SCIENCES,600385,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22020,5R01AI175439-02,Anti-flavivirus B cell response analysis to aid vaccine design,"Zika virus (ZIKV) is a member of flavivirus family that emerged as an infectious agent causing global health crisis during recent epidemics. ZIKV infection can cause Guillain-Barré syndrome in adults, and severe fetal neuromalformations and fetal death during pregnancy. ZIKV infection is primarily transmitted by mosquito bite, while sexual transmission and vertical transmission from infected pregnant women to fetus also contribute to the recent epidemic. Ideally, an effective ZIKV vaccine should provide sterilizing immunity that blocks the initial viral dissemination to prevent subsequent infection-caused morbidity. Currently, there is no approved ZIKV vaccine for disease prevention. The membrane (M) and envelope protein (E) expressed as prM-E form is a common antigen choice for current vaccine candidates against ZIKV, as neutralizing antibodies (nAb) against prM-E can prevent viral entry. However, such nascent PrM-E based ZIKV vaccines can increase the infectiousness of the dengue virus (DENV), another flavivirus of which endemic area largely overlaps with ZIKV. Due to the high degree of sequence homology between the E proteins of ZIKV and DENV, the ZIKV prM-E vaccine may stimulate the production of antibodies that are non-neutralizing but cross-reactive with the DENV E protein. In the event of a subsequent dengue virus infection, antibody-dependent enhancement (ADE) can occur when the suboptimal anti- ZIKV antibodies bind to the DENV virus, which thereby enhance the entry of DENV into host cells and exacerbate dengue symptoms. Strategies to prevent the induction of ADE-prone antibodies have been described recently for modified ZIKV immunogens, which unfortunately display suboptimal protection efficacy in small animals. Here, we focus on applying structure-based vaccine design to develop novel vaccine candidates with improved immunogenicity and reduced ADE potential for DENV infection. In preliminary study, our lead vaccine candidate formulated in optimized adjuvant showed nearly complete protection in immune mice challenged with ZIKV, and abolished ADE potential assessed by in vitro assays. Potent monoclonal ZIKV nAbs targeting the major ZIKV E protein nAb determinants including the quaternary E-dimer dependent epitope isolated from immune mice confirmed the design rationale. In this application, we will extend our effort via further immunogen designs guided by B cell/antibody response analysis and structural investigation of ZIKV E protein-antibody interactions to improve our lead vaccine candidate aiming at achieving sterilizing immunity, to evaluate in small animal models. If succeeds, this study will contribute to (i) the development of an effective and safe ZIKV vaccine, and (ii) deepening our understanding of immune response to flavivirus infections and immunizations.",,2028,UNIVERSITY OF MARYLAND BALTIMORE,694219,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P22021,1R01DE033391-01,Molecular mechanism of Zika virus-induced premature craniofacial suture closure,"Project Summary/Abstract The 2015-2016 Zika virus (ZIKV) outbreaks in the Americas have become a major global health concern due to their association with pre-natal birth defects such as microcephaly. Since the last outbreak, ZIKV has spilled back to the wildlife to establish persistent reservoir populations, and this has sparked concerns of future sylvatic transmissions that could ignite the next pandemic. Although ZIKV infection during pregnancy has been associated with microcephaly, it is important to note that premature cranial suture fusion (craniosynostosis) has been reported in 88% of babies with severe ZIKV infection and there is an ~22-fold increase in risk of developing craniosynostosis in ZIKV-infected babies compared to genetic occurrence. Aberrant osteogenic activation in the skull suture mesenchyme leads to premature cranial suture fusion, called craniosynostosis. In fact, ~30% of a prospective Brazilian cohort of ZIKV-exposed children showed delayed childhood neurodevelopment and neurosensory alterations. This indicates the craniofacial deformities are linked to severe neurodevelopmental defects. Despite serious health concern, no study has been done for ZIKV-induced craniosynostosis. Our preliminary observations in a 438 Brazilian cohort showed cranial suture fusions in ZIKV- infected infants. Intriguingly, prenatal ZIKV-infection. Using immunocompetent hSTAT2 KI mouse model, we demonstrated that prenatal ZIKV infection resulted in vertical transmission of virus to fetus side, resulting in severe birth defects such as microcephaly, brain calcification and craniosynostosis. Using this in vivo ZIKV mouse model, we have demonstrated significant downregulation of Gli1 expression, while osteogenic differentiation gene expression was significantly increased in sagittal suture tissues of ZIKV-infected mice. Surprisingly, ZIKV expression library screen showed that NS1 was sufficient to induce osteogenic differentiation in cranial osteoprogenitor cells. Based on these preliminary data, we hypothesize that ZIKV infects cranial suture mesenchyme cells to induce osteogenic differentiation of GLI1+ cells and craniosynostosis. Herein, I seek to address the following questions: (i) which host suture cell types are targeted for ZIKV-induced craniofacial suture fusion in vivo, (ii) characterize the host transcriptomic landscape of ZIKV-infected calvaria suture microenvironment, and (iii) which and how ZIKV proteins triggers craniofacial suture fusion upon infection. This proposal is highly innovative and translational, and potentially shed new insights to congenital ZIKV-induced fetal cranial suture anomalies.",,2028,CLEVELAND CLINIC LERNER COM-CWRU,402500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity,2024 +P22022,5R01NS120182-04,Neurodevelopment after postnatal Zika virus infection in infant macaques,"PROJECT SUMMARY / ABSTRACT Intense research has focused on the neurologic effects of prenatal Zika virus (ZIKV) infection; however, the consequences of postnatal infection early in life are understudied. Infants exposed to ZIKV in utero but born without microcephaly can develop postnatal microcephaly, neurologic dysfunction, and neurodevelopmental ab- normalities, highlighting the potential of ZIKV to cause ongoing damage after birth. This damage is likely related to the exponential maturation of the brain that occurs during the first 2 years of life, particularly in temporal, prefrontal and parietal regions important for emotional, social and executive functions, including learning, atten- tion and memory. Our group has previously reported that postnatal ZIKV infection causes abnormalities in brain structure, function, and behavior in a pilot study of infant rhesus macaques (RMs) infected postnatally. Here, we propose to extend the scope and duration our prior pilot study and generate novel data regarding the impact of postnatal ZIKV infection on the developing brain. The Objective of this application is to bring new mechanistic insights into postnatal ZIKV infection to address the existing knowledge gap regarding outcomes and host-virus interactions. We will use our postnatal ZIKV-RM model to interrogate the neurobehavioral impact of ZIKV infection at different stages of postnatal brain develop- ment, with approaches that span from single cells to whole animal. This model of postnatal ZIKV exposure allows us to generate key data on the mechanisms by which ZIKV and/or the immune response to infection leads to cellular changes that ultimately result in aberrant postnatal development of limbic structures and behavioral def- icits later in life. We hypothesize that 1) ZIKV and/or the immune response to infection disproportionately affects limbic structures in the postnatally developing brain; 2) cellular changes in these limbic structures lead to aberrant neurodevelopment and abnormal behaviors; and 3) there may be a period of vulnerability to ZIKV during post- natal brain development. We will test our hypotheses in these Specific Aims: 1) Determine the spectrum of abnormal behavior and cognition following ZIKV infection of infant RMs at different stages of brain development; 2) Identify developmental trajectories of brain structure and function following postnatal ZIKV infection of infant RMs at different stages of brain development; and 3) Define the neurodevelopmental pathways and cell types impacted by postnatal ZIKV infection. This work will include RM infants infected with ZIKV at 1 or 6 months of age (equivalent to 4 and 24 month old humans) as well as age- and rearing-matched and viral mimic controls, that over their first 2 years of life will undergo a series of detailed assessments including validated tests of soci- oemotional behavior and cognition, structural and functional brain imaging, brain histology, stereology and single cell and bulk cell transcriptomics. Our results may have important public health implications for children living in ZIKV-endemic/epidemic areas as well as for travelers to these regions.",,2025,EMORY UNIVERSITY,655903,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P22023,5R01AI170857-02,Molecular mechanisms linking viral replication and neuropathogenesis,"PROJECT SUMMARY/ABSTRACT Viruses that infect the developing brain, including Zika virus (ZIKV), cytomegalovirus, and rubella virus cause major birth defects. Microcephaly is one such birth defect, in which head and brain size are severely reduced, and is often accompanied by intellectual disability. This virally-inflicted neurological disease, or viral neuropathogenesis, can be caused by multiple mechanisms. One recently identified way ZIKV non-structural protein 4A (NS4A) causes microcephaly is by disrupting the human ANKLE2 protein. Interestingly, individuals with mutations in the gene encoding ANKLE2 suffer from microcephaly. ANKLE2 is conserved from worms to humans, and is essential for coordinating cell division during brain development. ANKLE2 derives this function in cell division and development by mediating protein interactions. NS4A physically interacts with ANKLE2 and disrupts brain development in an ANKLE2-dependent manner in a fruit fly model of brain development. ANKLE2 also promotes ZIKV replication. Taken together, these studies show that in the process of coopting a host protein for replication, ZIKV dysregulates an important developmental pathway. Thus, the NS4A-ANKLE2 protein interaction represents an important model to study viral neuropathogenesis and how it is connected to viral replication and hereditary disorders at the molecular level. The long-term goal of this work is to decipher how virus-host protein interactions impact virus replication and pathogenesis, as these discoveries will fuel therapeutic target identification and drug development. The objective of this proposal is to dissect the mechanisms by which the protein interaction between ZIKV NS4A and human ANKLE2 promote ZIKV replication and inhibit brain development. To accomplish this objective, we will test the central hypothesis that ANKLE2 promotes viral replication through its interaction with NS4A and by recruiting other host factors involved in ZIKV replication to sites of replication, and this disrupts physiological ANKLE2 protein interactions required for brain development. The following specific aims will test this hypothesis: Aim 1: Dissect the impact of the NS4A-ANKLE2 protein interaction in ZIKV replication and pathogenesis. Aim 2: Unravel the molecular function of ANKLE2 in ZIKV replication and pathogenesis. When completed, this work will delineate how a single virus-host protein interaction rewires a developmental pathway to facilitate virus replication and inflict neurological disease at the molecular level. This will reveal detailed biochemical insight into a virus-host protein interaction with amino acid-level resolution, new host factors that play a role in ZIKV replication, and previously unknown proteins key to brain development and disrupted in other hereditary developmental disorders. In the long term, the methods established here could be employed to uncover the molecular mechanisms behind other diseases with viral and hereditary etiologies.",,2028,UNIVERSITY OF CALIFORNIA AT DAVIS,493647,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2023 +P22024,5R01EY032149-04,Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection,"PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pathology, including loss of foveal reflex and macular pigment mottling, chorioretinal scarring, and macular atrophy. ZIKV has become endemic and local transmissions in the USA have been reported previously. The long-term effects of structural damage on vision, as well as the pathogenic processes of congenital ZIKV eye diseases are beginning to be understood. The signaling pathways governing normal eye development, which are dysregulated during ZIKV infection, are not well characterized. We recently carried out a series of experiments by establishing a ZIKV infectious ocular cell culture system and mouse models to understand the structural and molecular perturbations. For successful replication, viruses have evolved various strategies to evade innate immune response as well as to enhance the availability of cellular metabolites required to meet the heightened energy demand for viral genome synthesis. We found that the AMPKα, a cellular master energy sensor, is activated in the ZIKV-infected retinal cells. Moreover, pharmacological activation of AMPK resulted in attenuated ZIKV replication. Another interesting finding is that the YAP/TAZ factors in the tumor suppressor Hippo/SWH signaling pathway were induced early on, but degraded at later stage of ZIKV infection in RPE cells. Silencing YAP/TAZ resulted in reduced ZIKV replication. Since the energy sensor AMPK and Hippo signaling pathways control key cellular processes, including host antiviral responses, it is critical to understand the fundamental mechanism of these two pathways deregulation. We hypothesize that ZIKV modulates AMPK and Hippo signaling pathways in ocular cells to 1) increase intracellular metabolic resources, and 2) inhibit TBK1 to antagonize antiviral defense. These molecular changes can be orchestrated through viral coded factors resulting in the pathogenesis of ocular cell injury. The following specific aims will be investigated. Aim 1 focuses on systematically evaluating the role of AMPK- Hippo signaling on regulating antiviral response to ZIKV infection in RPE cells. The cross talk between these pathways will be investigated at the YAP/TAZ level. Pharmacological activation/inhibition, and gene knockout approaches in RPE cells will be carried out. Aim 2 is designed to elucidate the effect of ZIKV on Hippo and AMPK signaling pathways during retinal development. Human iPSC-derived 3D-retinal cup organoids will be used to investigate the link between retinal development and ZIKV-mediated deregulation of these key pathways. The ZIKV-encoded virulence factors regulating these pathways will be characterized. Aim 3 is to determine the effect of RPE-specific ablation of AMPK, TBK1, and Hippo signaling on the pathogenesis of ZIKV-induced chorioretinal atrophy in mice. This proposed study would yield novel insights into the pathogenesis of ZIKV in ocular diseases and identification of potential therapeutic targets.",,2024,UNIVERSITY OF CALIFORNIA LOS ANGELES,520349,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2021 +P22025,5R01NS125778-03,Role of microglia in neural infection,"ABSTRACT Zika virus (ZIKV) infection is associated with congenital ZIKV syndrome (CZS), including various brain anomalies and microcephaly. Our recent studies suggested that yolk sac (YS)-derived microglia (primary immune cells in the brain) and Peli1 (an E3 ubiquitin ligase) are involved in ZIKV infection and its associated CZS. However, it is unknown whether and how Peli1 contributes to the YS-microglia-mediated spread of ZIKV into brain, whether viral infection affects the normal function of microglia, and how such effects influence neural differentiation. Based on preliminary data, we hypothesize that Peli1 plays a critical role in fetal brain ZIKV infection via promoting YS-microglia-mediated ZIKV dissemination into fetal brain and via altering microglial function to affect neural differentiation. This hypothesis will be tested by two specific aims: 1) to determine how Peli1 promotes ZIKV infection of YS-microglia and virus dissemination from microglia to neural stem cells in fetal brains; and 2) to determine how Peli1 mediates microglial activation and alters neural differentiation after ZIKV infection. This integrative study employs biochemical and genetic manipulations in both in vivo animal models and in vitro mouse and human cell platforms. The outcomes will be evaluated by molecular, cellular, and neuroanatomical analyses. Understanding the molecular mechanisms underlying the role of microglia in ZIKV-related brain infection may lead to identification of new targets for prevention and treatment of ZIKV and other virus-mediated congenital neural infections.",,2026,UNIVERSITY OF TEXAS MED BR GALVESTON,464451,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P22026,7R01AI153724-03,Development of a vaccination platform for emerging flavivirus infections,"Project Summary: The Flavivirus genus (referred to as flaviviruses) consists of numerous emerging and re-emerging global pathogens of critical human significance. Endemic and emerging flaviviruses like dengue virus (DENV), Powassan virus (POWV), Zika virus (ZIKV), West Nile virus, Japanese Encephalitis virus and Yellow fever virus continue to spread and cause significant human disease. We have used RNA structural data from a conserved 3’ untranslated region (UTR) pseudoknot called xrRNA1 to develop an attenuation approach in a highly conserved structural region of the flavivirus 3’UTR for vaccine development. This approach allows us to 1) swap out flavivirus structural genes in our clone to rapidly develop chimeric, attenuated flavivirus vaccines for mosquito-borne flaviviruses and 2) provides a conserved site for attenuation for tick-borne flaviviruses like POWV. Based on our preliminary data, we hypothesize that xrRNA1-mutant, attenuated flavivirus vaccines will be safe, immunogenic, and provide protection from challenge in murine models of flavivirus disease. The objective of the proposed studies is to complete pre-clinical development of the attenuated flavivirus vaccine approaches. We will complete our proposed work in three aims that will evaluate immunologic and virologic outcomes following virus challenge after vaccination with candidate ZIKV vaccine (Aim 1), DENV vaccine (Aim 2), and POWV vaccine (Aim 3). We have recently published our data showing attenuation and immunogenicity of mutant xrRNA1 ZIKV (X1) in pregnant and non-pregnant mice. In this proposal, we will first evaluate the efficacy of ZIKV X1 vaccine in pregnant and non-pregnant mice challenged with ZIKV and DENV. These studies will allow us to evaluate ZIKV vaccine efficacy during pregnancy and evaluate the role of ZIKV vaccination in DENV disease enhancement. Next, we will use the attenuated, ZIKV vaccine platform developed in our laboratory using xrRNA1 structural data, insert chimeric pre-membrane and envelope structural genes from DENV1-4 and evaluate the attenuation, immunogenicity and efficacy of monovalent and quadrivalent DENV1-4 vaccine candidates. Given the complexity of DENV infection, we will evaluate disease enhancement and immunodominance in our quadrivalent vaccines along with efficacy. Third, we will expand our attenuation strategy in the X1 structure to tick-borne flaviviruses by utilizing our recently defined secondary structure of the POWV 3’UTR. Using POWV mutant vaccine candidates with targeted mutations in the X1 structure, we will characterize attenuation, immunogenicity, and efficacy of a POWV vaccine approach in a murine model of disease. The proposed studies will begin to translate our structural understanding of xrRNAs in the flavivirus 3’UTR into potential vaccine candidates. Moreover, this project will initiate studies focused on developing a platform for vaccine development for emerging flavivirus infections.",,2026,UT SOUTHWESTERN MEDICAL CENTER,413792,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2023 +P22027,5R01NS117149-04,Leveraging Zika virus and the immune system to treat glioblastoma,"PROJECT SUMMARY Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2 years. Despite aggressive therapy, most GBMs reappear within 6 months. A major reason for this outcome is because GBM stem cells (GSCs) are resistant to existing therapies. Currently, no treatment consistently kills these highly resistant cells. However, the Zika virus epidemic has provided us with a new approach to eradicate GSCs. ZIKV targets normal stem cells in the developing fetal brain, yet has minimal effects on differentiated neurons or the adult brain. Since GSCs share properties with neural stem cells, we investigated whether the natural honing and lytic activity of ZIKV could be harnessed to target and kill GSCs. We published the first use of ZIKV to kill GSCs. We showed that ZIKV kills GSCs in tumors removed from patients, with minimal impact on non-GSC tumor cells, called differentiated GBM cells. Importantly, normal human brain cells were not affected by ZIKV. After intracranial treatment with ZIKV, mice harboring gliomas survived more than twice as long as untreated mice and, in some cases, treated mice were long-term survivors. In addition to the resistance of GBM stem cell to chemoradiation, GBM is the hallmark example of an immunotherapy-resistant tumor. Importantly, we found that in vivo, ZIKV treatment reduces tumor size and extends survival beyond that expected for only anti-GSC effects. This suggested that ZIKV killing of GSCs may trigger an immune response against the remainder of the tumor. In more recent studies, we have found that CD8+ T cells are required for the efficacy of ZIKV as an oncolytic therapy in vivo. Our central hypothesis is that ZIKV elicits an anti-tumor immune response that could be made even more effective by combining it with existing immunotherapies. Aim 1 will determine how CD8+ T cells promote tumor clearance after ZIKV and Aim 2 will determine whether ZIKV can be combined with immunotherapy or standard-of-care for GBM to improve outcomes. Our long-term goal is to develop a new treatment for GBM by leveraging the immune system response to ZIKV.",,2025,WASHINGTON UNIVERSITY,388286,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2020 +P22028,5R21AI175733-02,Development of MS2045 for inhibition of Zika methyltransferase,"Project Summary The Zika virus (ZIKV) is a member of the Flavivirus genus that includes other arthropod-borne human pathogens such as dengue virus and West Nile virus, among others. ZIKV’s link to microcephaly in newborn infants and the Guillan-Barré syndrome in adults has invigorated measures to develop a vaccine, as well as efforts to develop antivirals based on targeting enzymatic activities central to the life cycle and survival of ZIKV. One such enzymatic activity is encoded by the methyltransferase (MTase) domain, located at the N-terminus of the nonstructural protein NS5. Taking a structure informed approach, we have succeeded in identifying a novel “lead-like” compound (MS2045) for the inhibition of ZIKV’s NS5 MTase activity and for blocking its replication. MS2045 provides a basis for further chemistry and the development of even more potent inhibitors. In aim 1, we will a) design MS2045 analogs with the capacity to establish specific interactions with unique amino acids of ZIKV MTase as a means to provide additional selectivity against the human RNA 5’-cap MTases; b) chemically synthesize these analogs and produce them to a purity of 95% for in vitro and cell-based assays, and for structural studies. In aim 2, we will a) perform biophysical assays to assess the ability of these analogs to selectively bind the ZIKV NS5-MTase as compared to the human RNA 5’-cap MTases and test their ability to inhibit RNA methylation; b) test these analogs in viral cell-based assays to assess their efficacy in blocking viral replication; c) determine structures ZIKV NS5-Mtase with select analogs for additional, iterative rounds of structure activity relationships (SARs). Collectively, these studies will help to identify analogs of MS2045 that can be potentially developed into potent and selective inhibitors of NS5-MTase from ZIKV (and other pathogenic flaviviruses)",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,190125,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P22029,5R01AI155735-04,Multiplexed Detection of Mosquito-Borne Viruses at the Point-of-Care,"Project Summary Dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), and Mayaro virus (MAYV) are all mosquito-borne RNA viruses. They are public health concerns because (1) DENV and CHIKV cause hundreds of millions of infections each year, with significant burdens in affected areas, (2) the outbreak of ZIKV in Brazil in 2015/2016 caused anxieties to general population due to its association with microcephaly of newborns, and (3) MAYV emerged in Central and Southern America recently and has the potential for epidemic spread. Because these virus infections have virtually identical clinical presentation and they often circulate concurrently, it is important to have a point-of-care (POC) testing platform to accurately identify virus infection for clinical management of patients, including different complications from these viruses. According to the Centers for Disease Control and Prevention (CDC), the current methods authorized for assessing DENV, ZIKV, and CHIKV infections include reverse transcription polymerase chain reaction (RT- PCR) assay and enzyme-linked immunosorbent assay (ELISA). However, these assays are carried out in laboratories, not at POC in a clinic or in an infected field. It is also important to note that virus infection can cause asymptomatic infections, up to 80% of ZIKV patients, 50% of DENV patients, and 28% of CHIKV patients, respectively. As a result, POC testing in the field will be more valuable for screening asymptomatic patients and monitoring possible virus transmission than a laboratory test because only symptomatic patients go to hospitals or clinics for seeking medical help or to be screened. To address the need, we propose to develop a POC diagnostic platform called Valve-enabled Lysis, paper- based RNA Enrichment, and RNA Amplification Devices (VLEAD). VLEAD will integrate sample preparationâ€Â"" including virus lysis and RNA enrichmentâ€Â""with nucleic acid amplification for simultaneous detection of these viruses. To achieve the goal, we aim to (1) develop multiplexed VLEAD for simultaneous detection of ZIKV, DENV, CHIKV and MAYV; (2) optimize VLEAD using various samples and compare the suitability of the device for urine, saliva and blood samples; and (3) validate VLEAD using clinical samples and compare VLEAD with the benchmark methods including conventional RT-PCR. The significance of the research lies in the following aspects. First, these mosquito-borne RNA viruses are a public health concern. An accurate and sample-to-answer virus detection platform at POC will be useful for clinical care and patient management. Second, a large percentage of these virus infections are asymptomatic, thus a non-invasive POC platform would be very beneficial for screening the general population in the infected area and monitoring virus transmission. Third, the VLEAD platform can be adapted for detecting other pathogens of interest, with a potential to have more societal impacts.",,2025,UNIVERSITY OF FLORIDA,334715,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P22030,5P20GM135004-05,Leveraging Zika virus driven myeloid cell responses to treat GBM,"Oncolytic viral therapy shows promise for high-grade solid tumors, but none have been shown to provide curative potential. This study explores the potential of harnessing the natural tropism of Zika virus (ZIKV) to target glioblastoma stem cells (GSCs) and reprogram the typically immune suppressive GBM tumor environment to an inflammatory, antigen-presenting environment that induces GBM-specific CD8+ T cell responses. The first goal of this proposal is to identify the cellular mechanisms that drive anti-tumor T cell responses following ZIKV treatment. Our research will examine the functional roles of two distinct myeloid cell subsets induced following ZIKV treatment - CCR2+ monocytes in the tumor microenvironment (TME) and dendritic cell subset-2 (DC-2s) in draining lymph nodes (dLN) - in driving anti-tumor T cell responses against GBM. Additionally, our study will examine the synergistic therapeutic potential of a highly novel Flt3 ligand therapy and ZIKV combination therapy as a strategy to activate both dendritic cell subset-1 (DC-1s) and DC-2, to maximize anti-tumor CD8+ T cell responses and subsequent GBM rejection. This research is significant because 1) it addresses the potential of ZIKV as an effective oncolytic virus for GBM treatment, 2) identifies key cellular mechanisms that contribute to its anti-tumor effects and 3) addresses the current failure of immunotherapy and maps a therapeutic path forward.",,2025,UNIVERSITY OF LOUISVILLE,198755,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2020 +P22031,5R01AI153434-04,Flavivirus immunity in endemic and non-endemic human cohorts,"PROJECT SUMMARY The global spread of the arthropod borne flaviviruses dengue (DENV1-4) and Zika (ZIKV) viruses are major global public health challenges. World health organizations are calling for scientific communities to respond to this emerging threat with vaccines, therapeutics and diagnostics. However, existing gaps in fundamental knowledge about DENV and ZIKV immunity, specifically how type-specific immunity to each serotype develops and is sustained, makes rational vaccine development particularly difficult. The dominant immunity model comes from human challenge studies on DENV (1910’s-1940’s) and posits that first infection induces neutralizing antibodies that provide life-long sterilizing immunity to repeat infections by the same (homotypic) serotype virus, and this model has been extended to ZIKV without rigorous evaluation. However, recent studies from DENV endemic regions provide evidence of homotypic re-infection and natural immune boosting over time and our preliminary data from a non-endemic, Portland, Oregon resident DENV and ZIKV immune cohort show type- specific Abs decay â€Â"" lose both potency and breadth - over time, calling into question sterilizing immunity and leading us to hypothesize that natural flavivirus (ZIKV and DENV) protective immunity is context dependent: in endemic transmission settings intermittent asymptomatic boosting maintains potency and breadth of virus specific immunity and in non-endemic or very low transmission settings potency and breadth of flavivirus immunity significantly wanes. To test this hypothesis, we propose to prospectively characterize and compare DENV and ZIKV immunity in a regularly re-exposed endemic cohort in Ponce, Puerto Rico with immunity in an un-boosted, non-endemic cohort of DENV immunes in Portland. This is a controversial and novel hypothesis that will call for substantial supporting evidence, hence we will compare and contrast three highly relevant and related markers of boosting between the two cohorts: The potency and breadth of neutralizing serum DENV and ZIKV specific Abs (Aim 1), the frequency of and potency of DENV and ZIKV non-structural protein 1 (NS1) specific antibodies (Aim 2), and the frequency and specificity of DENV and ZIKV specific memory B-cells (MBCs) (Aim 3). We expect to find that Abs and MBCs decline at a significantly greater rate in individuals from the non- endemic setting compared to the endemic setting supporting the hypothesis that boosting plays a critical role in natural immunity for these viruses, with implications for future vaccine development. Because MBCs are functionally linked to Abs, quantifying virus specific MBCs tests a mechanistic connection between repeat infection and Ab titer boosting. Our proposed work will comprehensively assess the role transmission context plays in flavivirus immunity using two highly relevant and mechanistically linked determinants (Ab and MBC). Irrespective of specific results, the knowledge obtained from the proposed work will be essential to DENV vaccine development and mechanistic understanding of flavivirus Ab mediated immunity.",,2026,OREGON HEALTH & SCIENCE UNIVERSITY,347331,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22032,5R01NS120895-04,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",353250,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22033,5K08AI168569-03,Defining Molecular Epitopes of Protective Antibodies to Flaviviruses,"Project Summary/Abstract: The objective of this K08 Mentored Clinical Scientist Career Award Application is to provide Dr. Alena Markmann with a strong foundation in human immunology and the latest methods for studying human immune cells before launching her independent research career on the human immune response to RNA viruses. Dr. Markmann is an Assistant Professor of Medicine, tenure track, at the University of North Carolina -Chapel Hill (UNC) School of Medicine with a joint appointment in the Department of Microbiology and Immunology. The candidate has expertise in and a strong track record of publications on antibody structure, antibody-antigen interactions and antibody neutralization of viruses. By strengthening her knowledge of adaptive immunity to RNA viruses and mastering the latest methods for analyzing antigen specific B cells, Dr. Markmann will study how the human immune response to emerging flaviviruses like dengue and Zika can suppress viral infection and disease or enhance viral replication and exacerbate disease. The candidate and her mentor Dr. Aravinda de Silva have designed a training plan that includes a rigorous research component along with didactic instruction, networking and presentation opportunities, team management skills as well as manuscript writing and grantsmanship. Together these skills will establish the methods and principles necessary for successful career development. Flaviviruses are enveloped positive stranded RNA viruses that pose a growing threat to the human population and cause millions of infections annually. They are vector-borne, transmitted by ticks and mosquitoes, and cause a spectrum of disease manifestations including febrile illness, encephalitides that can cause lifelong complications, Congenital Zika Syndrome and dengue hemorrhagic fever and shock syndromes. For the most part, flaviviral infection result in a neutralizing protective antibody response against the infecting virus, that can last for years after infection. The four dengue viruses however are very similar antigenically and in many cases, result in generating a broad cross-neutralizing antibody responseto dengue virus serotypes that individuals have not yet been exposed to. Thus far, no one has identified the viral target site of these broadly neutralizing dengue antibodies that exist in the serum. Furthermore, though we know of a few major targets of the Zika protective antibody response from studying memory B cells, we do not know what the serum targets are. Preliminary results suggest that in the case of Zika serum antibody responses, binding targets are correlated with known strongly neutralizing memory B cell-derived antibody targets. Thus, we hypothesize in Aim 1, that serum antibody responses will mirror memory B cell responses, but will likely come from a smaller number of B cell clones and be less cross-reactive with other flaviviruses. In Aim 2 we will identify the viral binding targets of broadly cross- neutralizing dengue antibodies from the serum. These studies will result in the ident ification of critical protective viral targets to both dengue and Zika viruses from the serum antibody compartment in order to inform successful vaccine design.",,2027,UNIV OF NORTH CAROLINA CHAPEL HILL,195235,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +P22034,5R01AI168107-02,Control of influenza virus induced type I interferon signaling during pregnancy,"PROJECT SUMMARY/ABSTRACT Infectious insults are common during pregnancy; over the nine months of gestation ~60% of pregnant women self-report at least one illness, with viral upper respiratory tract (URT) infections being the most common. Although URT-trophic viruses replicate in the respiratory epithelium, the induced inflammatory cytokines like type I interferon (IFN) circulate systemically and can access the placenta. Recent work has shown that virally induced type I IFNs can be major drivers of adverse effects on fetal development. URT infections during pregnancy, however, are not typically linked to birth defects or miscarriage. It was therefore unclear why maternal infection with a pathogen like an influenza virus, which also induces to fetal IFN exposure, would not compromise fetal health. We hypothesized that an uncharacterized IFN regulatory pathway was the answer to this apparent discrepancy. By performing a genome-wide CRISPR/Cas screen, we identified a G-protein coupled estrogen receptor 1 (GPER1) dependent signaling pathway that protected fetal health from type I IFN signaling during maternal influenza A virus (IAV) infection. Disruption of this pathway led to fetal phenotypes as severe as those caused by direct congenital infections. Importantly, the activities of this pathway were restricted to reproductive and fetal tissues; alterations of its activity had no measurable effect on maternal health during IAV infection. The major goal of this application is to understand how GPER1-mediated signaling normally protects fetal health from inflammatory maternal cytokines such as type I IFN. In aim 1, we will define how GPER1-induced GPCR signaling suppresses IFN-induced JAK/STAT signaling and interferon-stimulated gene expression. These experiments will define a previously unknown mechanism for control of IFN signaling. In aim 2, we will characterize where and when GPER1 signaling is required to protect fetal health, as well as the effects of GPER1 dysregulation on cell physiology both in vivo and in primary human placental organoid cultures. These experiments will allow basic mechanistic insights into how maternal inflammation compromises fetal development. Finally, in aim 3, we will explore the consequences of IFN signaling on placental structure/function when GPER1 is absent and also evaluate the potential of hyper-activating GPER1 signaling under the inflammatory conditions that normally harm fetal development. Together, these studies will not only allow for a more complete understanding of IFN regulatory mechanisms and the fetal/maternal immune response but could also serve as the basis for an eventual first-in-class treatment designed to protect the fetus from inflammation without compromising maternal immunity.",,2027,DUKE UNIVERSITY,649526,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2022 +P22035,5R21AI174052-02,Haplotype-resolved genome assemblies and chromosomal rearrangements in arboviral vector Aedes albopictus,"PROJECT SUMMARY The Asian tiger mosquito Aedes albopictus is native to Southeast Asia but in a few decades this species expanded its range to all continents except Antarctica. Aedes albopictus is capable of transmitting multiple arboviruses including dengueâ€Â""the leading arboviral disease of 21st centuryâ€Â""Chikungunya, and Zikaâ€Â""an emerging health threats for the world. Because of its remarkable ability to develop a photoperiodic diapause in the temperate climate, Ae. albopictus has the potential to spread these dangerous diseases further north. This project will develop haplotype-resolved chromosome-scale genome assemblies for multiple strains of Ae. albopictus and will test if adaptations to the temperate climate are associated with chromosomal rearrangements in this mosquito. Toward this end, we propose the following specific aims: 1) develop a haplotype-resolved chromosome-scale genome assemblies for four strains of Ae. albopictus including the Foshan strain; 2) improve the physical genome map for the Foshan strain of Ae. albopictus; and 3) identify chromosomal rearrangements in different populations of Ae. albopictus world-wide. Our long- term goal is to understand the genetic basis of the incredible phenotypic plasticity of Ae. albopictus that helps this mosquito to rapidly spread around the globe. We envision that the availability of the high-quality reference genome assemblies for multiple strains of Ae. albopictus will stimulate further genetic studies aimed at preventing mosquito-borne disease transmission.",,2024,VIRGINIA POLYTECHNIC INST AND ST UNIV,169113,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22036,5R21AI174093-02,The effect of the microbiota on male Aedes aegypti life history traits,"Project Summary: Mosquitoes transmit multiple diseases worldwide accounting for millions of disease cases and hundreds of thousands of deaths each year. The United States is not immune to the scourge of mosquito-borne disease, as mosquitoes in the USA can transmit dengue and Zika viruses as well as West Nile and La Crosse encephalitis virus. Mosquitoes are also a substantial nuisance that reduce quality of life and enjoyment of outdoor activity. Control of mosquito populations is the primary way we prevent disease transmission and nuisance issues. Many new methods of mosquito population reduction involve a modified version of a method called sterile insect technique (SIT) in which males are made reproductively sterile in a laboratory and released to mate with wild females. This results in zero offspring and a reduction in the population of that targeted mosquito species. SIT requires mass rearing of male mosquitoes in large rearing facilities and these males must be healthy and able to compete with wild males for mates. Here, we propose to investigate the potential impact the mosquito bacterial microbiota (i.e. bacteria in the mosquito body) may have on male Aedes aegypti mosquito traits that are relevant for SIT including longevity, body size, and ability to compete for mates. We will also investigate the way the microbiota affects the transcriptome of males. This work will be the first in-depth investigation into the role of the microbiota in male mosquito fitness traits and will provide key insight into ways the microbiota might be leveraged to improve SIT for mosquito control.",,2024,OHIO STATE UNIVERSITY,177188,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22041,5R01AI151004-05,Precision guided SIT for the control of vector-borne disease,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases. Dengue alone causes 90 million infections per year globally and like many vector-borne diseases, currently there are no drugs or vaccines to treat or prevent these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. In recent years, novel vector population suppression technologies have been created (e.g. RIDL and Wolbachia based systems), but production of mosquitoes for these programs is labor intensive and is limited in scalability and distribution. In this study, we will use a functional genomic screening approach to identify key sex determinate, female essential (FE) and male fertility (MF) genes in the dengue vector, Ae. aegypti. These studies will improve our understanding of the biology of this important vector and it can be used to inform the design of new genetic population suppression methods to control this vector. After these genes are identified and characterized, we will incorporate them into the design of precision guided sterile insect technique (pgSIT) technologies in an attempt to overcome limitations in traditional SIT control strategies. Sterile insect technique (SIT) is the gold standard for insect population control but has many limitations. Our proposed technology aims to simultaneously knock-out FE and MF genes using a binary CRISPR/Cas9 system in the Ae. aegypti disease vector. One line will target one or more female essential FE genes and one or more MF genes and the other line will express a Cas9. When these two lines are crossed, they create sterile, male progeny that are ready for release into a population suppression program. To generate these lines, initially we will characterize >40 candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be determined over many generations to ensure population stability. The design and integration of these transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression systems, including the impact of transgene expression timing and transgene location on the long-term stability of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies. In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",415756,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P22044,5R01AI155959-04,"Sample-to-Answer, Rapid, Multiplexed and PCR-Free Diagnostics of Arboviral Diseases in Resource Limited Settings","Arthropod-borne viruses (arboviruses) comprise many of the most important ‘emerging pathogens’ due to their geographic spread and their increasing impact on vulnerable human populations. There is urgent need for easy-to- operate and rapidly deployable diagnostic tools that can handle blood samples in a closed sample-to-answer manner. Here, we propose to develop a novel diagnostic technology that can detect viral antigens in an inexpensive, ultrasensitive, specific, and multiplexed manner. We will develop our novel approach into standalone tool with a detection capability at attomolar sensitivities (comparable to nucleic acid amplification tests) to diagnose arboviral infections with minimal user interference. The integrated diagnostic platform will utilize a novel surrogate approach, microfluidic integration, and a multiplexed detection scheme with the capacity to distinguish arboviral infections. The system will be designed to initiate diagnosis from serum/plasma/blood and provide a sample-to-answer diagnostic within less than 35 minutes using less than 100 Ã'µL blood samples at a cost of $2 per test. Collaborative work proposed for this NIH/NIAID R01 Grant involves integration of nanophotonic engineering (Yanik Group), molecular virology (Pinsky Group), and infectious diseases epidemiology (LaBeaud Group) to build and field-test our novel point-of-care viral diagnostic platform with Windward Islands Research and Education Foundation (WINDREF) and St. George’s University teams (Macpherson, Waechter and Noel Groups). Preliminary validation tests with patient samples will be initially performed at Stanford Medical Facility in collaboration with LaBeaud and Pinsky groups. Subsequently, three prototypes will be transferred to Grenada for field-testing initially at central laboratories then to resource-poor settings in small towns. Yanik group will provide the necessary expertise for integration of molecular and nanoengineering components and demonstration of a practical prototype as well as evaluating the application of prototype(s) developed under this proposal with patient samples (LaBeaud and Pinsky Groups). System will be iteratively optimized and a rugged platform suitable for field settings will be developed.",,2025,UNIVERSITY OF CALIFORNIA SANTA CRUZ,615061,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P22045,5R01AI148144-05,Clearance of Blood-Borne Arboviruses,"PROJECT SUMMARY Arboviruses cause serious human disease. Viremia level following arbovirus infection of vertebrates is a critical determinant of viral transmission cycles, global viral spread, and disease severity in individuals. Surprisingly, the factors that dictate viremia following arbovirus infection are poorly defined. We found that multiple arboviruses, including chikungunya (CHIKV), Ross River (RRV), o’nyong nyong (ONNV) and Zika viruses, are cleared from the circulation by phagocytic cells. Experiments in splenectomized mice showed that the spleen is dispensable for arboviral clearance. Instead, virus accumulates in the liver and clearance is independent of natural antibodies and complement factors, suggesting a non-opsonic mechanism. Consistent with this idea, clearance of circulating alphaviruses was blocked by competitive inhibitors of scavenger receptors (SRs) that mediate non- opsonic uptake of non-self and modified-self ligands. Remarkably, we found that single lysine (K) to arginine (R) mutations in the E2 glycoproteins of CHIKV and ONNV (E2 K200R), as well as RRV (E2 K251R), abrogated clearance of circulating alphavirus particles by phagocytic cells, and promoted rapid viral dissemination to distal tissues. Moreover, substitution of CHIKV E2 K200 with a variety of other amino acids also allows for clearance evasion, suggesting a specific interaction between key K residues and a host factor. Ks are targets for post- translational modification (PTM), and mass spectrometry analysis of E2 in virions revealed that CHIKV E2 K200 is ubiquitinated. These experiments have revealed a previously unrecognized pathway that controls arbovirus viremia and dissemination in vertebrates. We hypothesize that PTM of key Ks in viral glycoproteins licenses the capture of circulating arboviruses via SRs expressed on liver Kupffer cells (KCs). In Specific Aim 1, the cell types that capture circulating arboviruses will be defined. We also will determine the role of KCs in viral clearance and dissemination, and the development of anti-viral immunity. Finally, we will evaluate the role of phagocytic cells, and KCs specifically, in the clearance of a genera-spanning panel of arboviruses. In Specific Aim 2, we will define the spectrum of blood-borne arboviruses susceptible to SR-mediated clearance. We will use ELISA and cellular binding assays to determine the murine and human SR(s) that bind virus particles. Using SR knockout mice, we will determine the role of specific SRs in clearance of circulating arboviruses. In Specific Aim 3, we will define the role of E2 ubiquitination in the clearance of circulating CHIKV and RRV. We will use mass spectrometry-based proteomics to determine K residues in arboviral particles that are modified with ubiquitin or other PTMs. Finally, we will use a collection of reverse genetics systems to define the role of specific modified Ks in arboviral clearance from the circulation. This work will provide new mechanistic understanding of arbovirus clearance from the circulation. Elucidating these mechanisms could provide new insight into viral transmission, dissemination, and pathogenesis, identify new risk factors of severe disease, and reveal new therapeutic targets for the treatment of arboviral disease.",,2025,UNIVERSITY OF COLORADO DENVER,418933,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae | Unspecified,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22047,5R01HD102445-04,Childhood Outcome After In Utero ZIKV Exposure,"PROJECT SUMMARY Clinically normal children exposed to Zika-virus (ZIKV) in utero may evidence abnormal neurodevelopment during the first few years of life even in the absence of the severe phenotype of congenital Zika syndrome (CZS). This is an important problem because the majority of children with in utero ZIKV exposure do not develop CZS but are at risk for neurodevelopmental abnormalities as they mature. The risk for neurodevelopmental impairments at school age in children with in utero ZIKV exposure, who do not have CZS, is not known because children have neither reached nor been studied at this critical age. The long-term goal is to recognize the spectrum of neurologic outcomes for children exposed to ZIKV in utero, which will enable appropriate follow-up guidelines, educational interventions, and therapies to support all children exposed to ZIKV. The objective of this application is to identify school age abnormalities in neurodevelopment and the domains affected and to evaluate for brain structural and functional differences among children in Colombia and in the US with ZIKV exposure in utero who do not have CZS. Guided by strong preliminary data, we will test two specific hypotheses: 1) that executive and motor function will be negatively impacted in ZIKV-exposed children compared to controls; and 2) that quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls. The children will be followed at age 5 and 7 years using a specifically designed set of neurodevelopmental assessment tools and quantitative structural and functional neuroimaging. Neurodevelopment will be assessed by an approach utilizing validated questionnaires and child assessments that measure executive function, behavior, motor function, and intellectual ability. The advanced brain MRI will provide a multimodal assessment of brain structure and function. The approach is innovative because of access to two uniquely well characterized cohorts, one from the Caribbean coast of Colombia who had sequential fetal and neonatal neuroimaging and had early neurodevelopmental evaluations and a cohort from a congenital Zika program in the United States with exposure by travel or emigration. The proposed research is significant, because it will address a key question in child health by focusing on neurodevelopmental abnormalities in children following in utero ZIKV exposure that can manifest at school age. Ultimately, such knowledge has the potential to immediately inform the development of guidelines for neuropsychological and imaging assessment at school age for children with in utero exposure to ZIKV. Completion of the aims will improve identification of abnormal neurologic outcomes in children who had exposure to ZIKV in utero. The knowledge to be gained from this work is essential to be done now and is important to families, care providers, public health policy authorities, and federal agencies. It may be also applicable to future congenital infectious epidemics and potentially other perinatal exposures.",,2025,CHILDREN'S RESEARCH INSTITUTE,684373,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +P22048,5R01EY032495-03,Role of Zika virus (ZIKV) infection in glaucoma pathobiology,"PROJECT SUMMARY The overall goal of this project is to investigate the role of Zika virus (ZIKV) in glaucoma pathobiology. ZIKV is an emerging viral pathogen that causes microcephaly and leads to severe ocular complications in newborns born to ZIKV infected mothers. Although the ocular manifestations of ZIKV are primarily reported to affect the posterior segment of the eye resulting in chorioretinal atrophy, withering of the retina and choroid, and optic nerve abnormalities, several clinical case reports showed the involvement of the anterior segment resulting in glaucoma. Studies from our laboratory, as well as those of others, have shown that ZIKV can cause glaucomatous pathology including an increase in intraocular pressure (IOP), retinal ganglion cell (RGC) loss, and optic nerve damage. The offspring of ZIKV infected dams have shown increased IOP and RGC loss and the presence of anti-flavivirus-antibody in these mice correlates with significantly enhanced glaucoma pathology due to antibody-dependent enhancement. Until the recent ZIKV epidemics, glaucoma has been primarily considered as a genetic and age-related disease and has not been reported among infants exposed to infection during gestation. Several studies have now reported that ZIKV can cause congenital glaucoma in infants born from mothers who were infected during pregnancy. Considering the fact that there is an endemic transmission of ZIKV in >84 countries, it is imperative to investigate the link between ZIKV and glaucoma to develop new prognostic and therapeutic tools to combat this global health threat. Our laboratory has developed several in vitro and in vivo models to study the pathobiology of ocular ZIKV infections. In our recent study, we reported that ZIKV can infect and replicate in human primary Trabecular Meshwork cells (HTMC). More recently, we performed RNAseq analysis and discovered that ZIKV infection of HTMC leads to transcriptomic alteration and dysregulation of several pathways including those that modulate ER stress response, autophagy, hypoxia, and ECM organization. Furthermore, ZIKV-infected mice exhibited increased IOP, ER stress, and autophagy in the anterior segment of the eye. ZIKV infection also caused RGC death and loss of RGC and optic nerve damage leading to disruption of anterograde axonal transport. Based on these novel findings, we hypothesize that ZIKV induces ER stress and autophagy resulting in TM death and dysfunction, increased IOP, and the development of glaucoma. Two specific aims are proposed to test this hypothesis. Aim 1 will determine the role of ZIKV induced ER stress in TM dysfunction and the pathobiology of glaucoma using C57BL/6 (WT) and IFNAR1-/- mice/pups and whether the reduction of ER stress alleviates ZIKV induced glaucomatous pathology. Aim 2 will investigate the role of autophagy using HTMC, and mouse models and evaluate the therapeutic efficacy of an FDA approved drug, hydroxychloroquine (HCQ) in ZIKV induced glaucoma. The anticipated results will establish the role of ZIKV infection in the pathogenesis of glaucoma and elucidate the molecular mechanisms and pathway-mediated therapeutic targets for future treatments.",,2026,UNIVERSITY OF MISSOURI-COLUMBIA,367879,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2021 +P22049,5R01AI149486-04,Understanding the mechanisms of antibody-mediated transcytosis of ZIKV within the placenta,"Humoral immunity is an essential component of the immune response to flavivirus infection. Primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly apparent that secondary infection with a closely related flavivirus strain can result in immunological cross-reactivity; however, the consequences to infection outcome are hotly debated and controversial. Zika virus (ZIKV) is a mosquito-borne flavivirus, which has a high degree of sequence and structural homology to Dengue virus (DENV), and is responsible for continuing epidemics of fetal congenital malformations within the Americas since its introduction to Brazil in 2015. Prior flavivirus exposure has been strongly associated with generation of cross-reactive antibodies that bind to and/or neutralize ZIKV. A unique aspect of ZIKV pathogenesis is the ability of the virus to seed infection within the placenta, however, the mechanisms of transplacental ZIKV infection are not well understood. The overall goal of this proposal is to understand how cross-reactive antibodies facilitate ZIKV transcytosis and seed infection of the placenta. The placenta is composed of anchoring chorionic villi, which penetrate the uterine wall, as well as floating chorionic villi that are bathed in maternal blood pooling in the intervillous space. Recent epidemiological observations found that between 20-50% of pregnant women with possible ZIKV exposure had detectable ZIKV RNA in the placenta. Another report found that ZIKV can persist in the placenta for over 200 days post mother onset of Zika symptoms. We discovered that Hofbauer cells, fetally- derived placental macrophages located within the villus stroma, are permissive for ZIKV infection. To identify a potential mechanism by which ZIKV gains access to the villous stroma, we recently evaluated the impact of cross-reactive dengue antibodies in mediating transplacental infection. Using an ex vivo placental explant model, we observed profound enhancement of ZIKV infection of human mid-gestation floating chorionic villi with ZIKV immune complexes generated using either DENV or ZIKV cross-reactive convalescent serum or monoclonal antibodies. Similar to histological analysis of placenta from infected pregnant mothers, ZIKV replicated exclusively within Hofbauer cells. Based on these observations, we hypothesize that the Fab fragment (specificity for ZIKV) and the Fc domain (affinity for FcRn and FcγR) of IgG impacts antibody-mediated ZIKV transplacental infection. Moreover, we believe that gestational age of the placenta dynamically influences the efficiency of ZIKV transcytosis and placental infection. Moreover, we believe that gestational age of the placenta dynamically impacts ZIKV transcytosis and placental infection. In this proposal, we seek to address the following outstanding questions: 1) How does IgG antibody specificity, affinity and Fc/FcRn interactions impact ZIKV transplacental infection? and 2) How does placental gestational age impacts antibody-mediated infection of Hofbauer cells? Our studies will likely reveal therapeutic targets and provide insights for development a vaccine to protect against ZIKV infection.",,2025,EMORY UNIVERSITY,754544,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +P22050,5R21AI149385-02,ADAR1-mediated antiviral response in Zika virus (ZIKV) infection,"Project Summary In response to viral infections, host cells trigger an innate/anti-viral immune response, predominantly by producing the interferons (IFNs) and IFN-stimulated genes (ISGs). These anti- viral responses promote inflammation, immune cell activation, and viral clearance. We recently reported that retinal pigment epithelium (RPE) and retinal vascular or choroidal endothelium are highly permissive to Zika virus (ZIKV) infection and elicit antiviral response with increased production of IFNs and ISGs. The transcriptomic analysis of ZIKV-infected RPE revealed the induction of adenosine deaminases acting on RNA1 (ADAR1), a potent ISG, which can exert pro- or antiviral activity by A-to-I editing of the host and viral RNA. The role and mechanisms of action of ADAR1 during ZIKV and related flaviviruses have not been studied till now. Our preliminary studies show that 1) ADAR1 is up-regulated at the transcript, as well as, protein levels upon ZIKV infection in RPE cells, and 2) ADAR1 overexpression reduced, while ADAR1 knockdown increased, ZIKV replication in RPE cells. These findings led us to investigate the role of ADAR1 in retinal innate immunity to ZIKV and other flaviviruses. Thus, the overall goal of this proposal is to determine the mechanisms of antiviral actions of ADAR1 in attenuating ZIKV replication in RPE cells (Aim 1); and to determine the consequences of ADAR1 ablation and ADAR1 overexpression on ZIKV-induced chorioretinal atrophy in a mouse model (Aim 2). The proposed studies will broaden and deepen our knowledge of the antiviral response during ocular ZIKV infection. Our studies could also identify new targets and treatment modalities based on the RNA editing ability of the host.",,2025,WAYNE STATE UNIVERSITY,192500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22051,3R01HD102445-04S1,ADMIN SUPPL: Childhood outcome after in utero ZIKV exposure,"PROJECT SUMMARY Clinically normal children exposed to Zika-virus (ZIKV) in utero may evidence abnormal neurodevelopment during the first few years of life even in the absence of the severe phenotype of congenital Zika syndrome (CZS). This is an important problem because the majority of children with in utero ZIKV exposure do not develop CZS but are at risk for neurodevelopmental abnormalities as they mature. The risk for neurodevelopmental impairments at school age in children with in utero ZIKV exposure, who do not have CZS, is not known because children have neither reached nor been studied at this critical age. The long-term goal is to recognize the spectrum of neurologic outcomes for children exposed to ZIKV in utero, which will enable appropriate follow-up guidelines, educational interventions, and therapies to support all children exposed to ZIKV. The objective of this application is to identify school age abnormalities in neurodevelopment and the domains affected and to evaluate for brain structural and functional differences among children in Colombia and in the US with ZIKV exposure in utero who do not have CZS. Guided by strong preliminary data, we will test two specific hypotheses: 1) that executive and motor function will be negatively impacted in ZIKV-exposed children compared to controls; and 2) that quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls. The children will be followed at age 5 and 7 years using a specifically designed set of neurodevelopmental assessment tools and quantitative structural and functional neuroimaging. Neurodevelopment will be assessed by an approach utilizing validated questionnaires and child assessments that measure executive function, behavior, motor function, and intellectual ability. The advanced brain MRI will provide a multimodal assessment of brain structure and function. The approach is innovative because of access to two uniquely well characterized cohorts, one from the Caribbean coast of Colombia who had sequential fetal and neonatal neuroimaging and had early neurodevelopmental evaluations and a cohort from a congenital Zika program in the United States with exposure by travel or emigration. The proposed research is significant, because it will address a key question in child health by focusing on neurodevelopmental abnormalities in children following in utero ZIKV exposure that can manifest at school age. Ultimately, such knowledge has the potential to immediately inform the development of guidelines for neuropsychological and imaging assessment at school age for children with in utero exposure to ZIKV. Completion of the aims will improve identification of abnormal neurologic outcomes in children who had exposure to ZIKV in utero. The knowledge to be gained from this work is essential to be done now and is important to families, care providers, public health policy authorities, and federal agencies. It may be also applicable to future congenital infectious epidemics and potentially other perinatal exposures.",,2025,CHILDREN'S RESEARCH INSTITUTE,136488,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Clinical characterisation and management,Post acute and long term health consequences,2020 +P22052,5R01AI150837-04,Enhanced susceptibility to Zika virus during pregnancy: a role for maternal dengue antibodies,"Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is closely related to dengue virus (DENV). Since its discovery in 1947, ZIKV remained relatively unnoticed, causing small, local outbreaks primarily in parts of Africa and Asia, and was associated with minor symptoms, such as mild fever. However, in the last decade, ZIKV started to spread geographically across the Pacific islands, eventually reaching South America, where it caused an explosive outbreak that started in Brazil in 2015 and rapidly spread to other South and Central American countries. This has been accompanied by a startling link between ZIKV infection during pregnancy and the development of birth defects among fetuses and babies, including microcephaly. It is unclear what factors may have led to the massive ZIKV outbreak or the severe disease manifestations in the Americas, but one potential variable is that much of the at-risk population in the Americas has preexisting immunity to DENV. It is well documented that preexisting immunity to one serotype of DENV can alter the disease pathogenesis of a subsequent infection with a different DENV serotype, a phenomenon called antibody-dependent enhancement (ADE). Because ZIKV outbreaks have occurred in regions around the world where DENV is endemic and due to the high degree of relatedness of ZIKV and DENV, it is critical to understand and characterize the extent to which prior infection with DENV exacerbates ZIKV disease. In this application, we will focus on how DENV antibodies impact ZIKV infection in the context of pregnancy by utilizing three model systems (immunocompromised Stat2-/- mice, immunocompetent humanized STAT2 knock-in mice, and human placental explants infected with ZIKV ex vivo).",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,421878,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +P22053,5R01AI148264-04,Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates,"Abstract Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that recently caused an outbreak in the Americas. The establishment of ZIKV transmission cycle in tropical/sub-tropical regions that are endemic to other close-related flaviviruses such as Dengue virus (DENV) has raised concerns, mainly by their cross-immunological interactions and the implications of this for development of severe clinical manifestations. Several groups have demonstrated that DENV-immune serum from humans can enhance ZIKV infection in vitro and in vivo in an immunodeficient mice model. This phenomenon known as Antibody Dependent-Enhancement (ADE) has been linked to severe dengue clinical manifestations. Little is known about the effect of a previous immunity to ZIKV on a subsequent DENV infection. It is highly necessary to characterize correlates of protection in the control of a heterologous secondary DENV or ZIKV infection in the presence of previous DENV or ZIKV immunity in an immunological competent animal model that resemble the human immune system like the Non- Human Primates. Our group have preliminary data showing a potential protective role of the cellular immune response in dengue- immune or ZIKV-immune subjects during a heterologous secondary infection with ZIKV or dengue. The overall hypothesis behind this work is that the cross-primed cellular immune response may be critical controlling the DENV and ZIKV infection and provides heterologous protection against each other. To test this hypothesis, we propose a series of straightforward experiments by depleting the CD4+ or CD8+ or CD20+ cells at different time points before a primary or a secondary infection with dengue or ZIKV. This type of experiment has not been performed before in NHP. For these experiments we will use rhesus macaques bred and housed at the Caribbean Primate Research Center that has proven to be the purer Indian-origin macaque population of all populations in the USA or imported animals, without having a significant level of inbreeding. For first time in any study in the flavivirus field, we will use a large data on the MHC typing of this population to characterize specific CD4 and/or CD8 T cells epitopes playing a role in the T cells immune response against dengue and ZIKV. Understanding correlates of protection between ZIKV and DENV is essential to anticipate the outcome of the secondary infection, the design of diagnostics methods and more relevant, to support the design of highly effective ZIKV and DENV vaccines in the scenario of previous DENV or ZIKV immunity, respectively. Undoubtedly, NHP provide us with a unique immunological tool very close to the human system to provide the answers to the questions we are outlying on this application.",,2024,UNIVERSITY OF PUERTO RICO MED SCIENCES,677445,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22054,1R01AI175439-01,Anti-flavivirus B cell response analysis to aid vaccine design,"Zika virus (ZIKV) is a member of flavivirus family that emerged as an infectious agent causing global health crisis during recent epidemics. ZIKV infection can cause Guillain-Barré syndrome in adults, and severe fetal neuromalformations and fetal death during pregnancy. ZIKV infection is primarily transmitted by mosquito bite, while sexual transmission and vertical transmission from infected pregnant women to fetus also contribute to the recent epidemic. Ideally, an effective ZIKV vaccine should provide sterilizing immunity that blocks the initial viral dissemination to prevent subsequent infection-caused morbidity. Currently, there is no approved ZIKV vaccine for disease prevention. The membrane (M) and envelope protein (E) expressed as prM-E form is a common antigen choice for current vaccine candidates against ZIKV, as neutralizing antibodies (nAb) against prM-E can prevent viral entry. However, such nascent PrM-E based ZIKV vaccines can increase the infectiousness of the dengue virus (DENV), another flavivirus of which endemic area largely overlaps with ZIKV. Due to the high degree of sequence homology between the E proteins of ZIKV and DENV, the ZIKV prM-E vaccine may stimulate the production of antibodies that are non-neutralizing but cross-reactive with the DENV E protein. In the event of a subsequent dengue virus infection, antibody-dependent enhancement (ADE) can occur when the suboptimal anti- ZIKV antibodies bind to the DENV virus, which thereby enhance the entry of DENV into host cells and exacerbate dengue symptoms. Strategies to prevent the induction of ADE-prone antibodies have been described recently for modified ZIKV immunogens, which unfortunately display suboptimal protection efficacy in small animals. Here, we focus on applying structure-based vaccine design to develop novel vaccine candidates with improved immunogenicity and reduced ADE potential for DENV infection. In preliminary study, our lead vaccine candidate formulated in optimized adjuvant showed nearly complete protection in immune mice challenged with ZIKV, and abolished ADE potential assessed by in vitro assays. Potent monoclonal ZIKV nAbs targeting the major ZIKV E protein nAb determinants including the quaternary E-dimer dependent epitope isolated from immune mice confirmed the design rationale. In this application, we will extend our effort via further immunogen designs guided by B cell/antibody response analysis and structural investigation of ZIKV E protein-antibody interactions to improve our lead vaccine candidate aiming at achieving sterilizing immunity, to evaluate in small animal models. If succeeds, this study will contribute to (i) the development of an effective and safe ZIKV vaccine, and (ii) deepening our understanding of immune response to flavivirus infections and immunizations.",,2028,UNIVERSITY OF MARYLAND BALTIMORE,784842,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P22055,5U01AI153416-03,"Living in the post-Zika world: Impact of interactions between dengue and Zika viruses on diagnostics, antibody dynamics, and correlates of disease risk","SUMMARY Worldwide, over 3 billion people are at risk of infection and disease caused by dengue virus 1-4 (DENV1-4) and Zika virus (ZIKV), both potentially severe flaviviral diseases transmitted by Aedes mosquitoes. The devastating effects of endemic dengue across the tropics and subtropics are well documented. The recent Zika pandemic galvanized research as Zika swept across Latin America. Three years after the peak of the Zika pandemic, major dengue epidemics have started to re-occur; however, the future of flaviviral disease across areas with widespread ZIKV immunity is unknown. In this R01, we propose to develop new tools and address key knowledge gaps in flaviviral transmission and immunological interactions between DENV and ZIKV to understand how widespread ZIKV immunity impacts subsequent dengue disease and to inform evaluation of dengue and Zika clinical vaccine trials and post-licensure studies. Based on our serological, epidemiological, and clinical data to date, our overall hypothesis is that DENV1-4 and ZIKV are antigenically closely related and that immune interactions mutually affect transmission and disease severity. We will address this hypothesis with the ongoing Pediatric Dengue Cohort Study (PDCS, 2004-present), a community-based prospective cohort study in Managua, Nicaragua, following ~4,000 children, now in its 17th year. Samples from the PDCS, as well as companion studies in Managua, provide documented infection and disease data, as well as banked serum samples for over a decade before the arrival of ZIKV. The proposed study extends the cohort, ensuring that we are able to fully document the interactions of these viruses from the pre- to post-Zika eras. In Aim 1, we will develop innovative serologic tools based on glycan-fusion-loop-masked envelope proteins and new algorithms to distinguish DENV and ZIKV infection histories, critical for vaccination and epidemiological studies of dengue and Zika. We will then test our hypothesis that pre-existing ZIKV immunity can enhance disease severity caused by DENV3 but protect against DENV1. In Aim 2, we will measure changes in anti-DENV and anti-ZIKV antibody-mediated immunity over time, estimate annual changes in protective and enhancing population immunity to each virus, collect entomological data, and use modeling approaches to evaluate popula- tion susceptibility to DENV and ZIKV infection and the potential for future epidemics by incorporating immunolo- gical and entomological data. In Aim 3, we will identify determinants of protective and disease-enhancing anti- body-mediated immunity of prior DENV infection on Zika and prior ZIKV infection on dengue disease and severity. With support of expert collaborators, we will use state-of-the-art tools (e.g., new monoclonal antibodies, innovative flavivirus antigens, and antibody Fc profiling) to analyze specific infection histories and uncover potential immune correlates. Overall, this program will define new vaccine companion diagnostic assays, the dynamics of the antibody response to DENV and ZIKV, and correlates of protection and pathogenesis for dengue and Zika, which should be useful for the development and evaluation of dengue and Zika vaccines.",,2026,UNIVERSITY OF CALIFORNIA BERKELEY,1002425,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences,2021 +P22056,5R01AI163188-03,Development of a Replicon RNA-based Vaccine against Dengue and Zika,"ABSTRACT The long-term goal of this project is to develop a dengue-Zika vaccine that provides protection against the four serotypes of dengue (DENV1-4) and Zika (ZIKV) viruses with maximal safety and efficacy. To date, flavivirus vaccine development has focused on the induction of neutralizing antibodies (nAbs), as they have been assumed to be the key mechanism for protection against natural infection. However, DENV and perhaps ZIKV are unusual in that weak Ab responses to vaccination or prior infection can induce antibody-dependent enhancement (ADE) of infection and pathogenesis during subsequent reinfections. In fact, DENV disease with severe sequalae has been documented in children given the only currently licensed DENV vaccine. Thus, the primary objective of this application is to develop an effective vaccine against DENV and ZIKV that cannot mediate ADE. We hypothesize that this vaccine will need to elicit both strong nAb responses and strong T cell effector responses that will counterbalance the presence of any ADE-mediating Abs, based on our work investigating the interplay between Ab and T cell responses to DENV and ZIKV. In particular, we have shown that CD8 T cells mediate cross- protection against heterotypic DENV and ZIKV infections, and that DENV vaccine-elicited CD8 T cells can prevent ADE. In addition, our preliminary data show that an RNA replicon-based vaccine expressing ZIKV nonstructural protein 3 elicits only T cell but not nAb responses and confers protection against ZIKV challenge in mice. Thus, we hypothesize that our combinatorial DENV-ZIKV vaccine expressing both Ab- and T cell-targeting proteins of DENV1-4 and ZIKV will produce humoral and cellular immune responses that provide robust, long-term protection against all five viruses. We will test this hypothesis by achieving the following Specific Aims: 1) To evaluate immunogenicity and efficacy of a DENV-ZIKV vaccine. 2) To determine the durability and mechanistic underpinnings of DENV-ZIKV vaccine-induced protective immunity.",,2026,LA JOLLA INSTITUTE FOR IMMUNOLOGY,721849,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P22057,5R01AI153130-04,Early neural predictors and neuropathogenesis of sensorimotor neurodevelopmental deficits in macaque infants exposed to Zika virus in utero,"PROJECT SUMMARY Prenatal exposure to the Zika virus (ZIKV) poses a threat to the fetus, putting the neonate at risk for significant birth defects (termed congenital Zika syndrome) and neurodevelopmental deficits developing during early child- hood. There are currently no predictors to indicate which children will develop deficits and the neuropathologies underlying these deficits is not defined. It is critical to predict which infants will later develop deficits to max- imize long-term sensorimotor development and functional outcomes. Furthermore, understanding underlying neuropathogenesis is necessary to develop targeted interventions. The purpose of this grant is to define the long-term neurodevelopmental outcomes of ZIKV by rapidly obtaining data from highly controlled studies of rhesus macaques. Specifically, we will: Aim 1: Characterize sensorimotor neurodevelopmental outcomes in macaques with prenatal ZIKV expo- sure. Behavioral assessments focused on sensorimotor development may highlight the distinct developmental trajectories and increased deficits with age in ZIKV-exposed rhesus macaques. Because macaques develop more quickly than humans, sensorimotor neurodevelopmental differences that occur by year 3 may predict future impacts in children born with prenatal ZIKV exposure. Aim 2: Identify early neural predictors of sensorimotor neurodevelopmental deficits in ZIKV-exposed infant macaques with quantitative MRI, hearing and visual studies. We will describe differences between ZIKV-exposed and mock-infection control infants and identify individual differences within ZIKV-exposed in- fants to determine the full spectrum of brain abnormalities. Aim 3: Define neuropathology underlying sensorimotor neurodevelopmental deficits with quantitative brain histopathology. Using cellular quantification and organization of brain nuclei, we aim to identify the neu- ropathogenesis of congenital Zika syndrome to better create appropriate, targeted interventions for children. This study utilizes a large cohort of ZIKV-exposed infant macaques that have been born in other NIH-funded studies and capitalizes on our collaborative team of experts in neuropathology, neurodevelopment and neu- roradiology.",,2025,UNIVERSITY OF WISCONSIN-MADISON,751867,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P22058,5R01NS120182-03,Neurodevelopment after postnatal Zika virus infection in infant macaques,"PROJECT SUMMARY / ABSTRACT Intense research has focused on the neurologic effects of prenatal Zika virus (ZIKV) infection; however, the consequences of postnatal infection early in life are understudied. Infants exposed to ZIKV in utero but born without microcephaly can develop postnatal microcephaly, neurologic dysfunction, and neurodevelopmental ab- normalities, highlighting the potential of ZIKV to cause ongoing damage after birth. This damage is likely related to the exponential maturation of the brain that occurs during the first 2 years of life, particularly in temporal, prefrontal and parietal regions important for emotional, social and executive functions, including learning, atten- tion and memory. Our group has previously reported that postnatal ZIKV infection causes abnormalities in brain structure, function, and behavior in a pilot study of infant rhesus macaques (RMs) infected postnatally. Here, we propose to extend the scope and duration our prior pilot study and generate novel data regarding the impact of postnatal ZIKV infection on the developing brain. The Objective of this application is to bring new mechanistic insights into postnatal ZIKV infection to address the existing knowledge gap regarding outcomes and host-virus interactions. We will use our postnatal ZIKV-RM model to interrogate the neurobehavioral impact of ZIKV infection at different stages of postnatal brain develop- ment, with approaches that span from single cells to whole animal. This model of postnatal ZIKV exposure allows us to generate key data on the mechanisms by which ZIKV and/or the immune response to infection leads to cellular changes that ultimately result in aberrant postnatal development of limbic structures and behavioral def- icits later in life. We hypothesize that 1) ZIKV and/or the immune response to infection disproportionately affects limbic structures in the postnatally developing brain; 2) cellular changes in these limbic structures lead to aberrant neurodevelopment and abnormal behaviors; and 3) there may be a period of vulnerability to ZIKV during post- natal brain development. We will test our hypotheses in these Specific Aims: 1) Determine the spectrum of abnormal behavior and cognition following ZIKV infection of infant RMs at different stages of brain development; 2) Identify developmental trajectories of brain structure and function following postnatal ZIKV infection of infant RMs at different stages of brain development; and 3) Define the neurodevelopmental pathways and cell types impacted by postnatal ZIKV infection. This work will include RM infants infected with ZIKV at 1 or 6 months of age (equivalent to 4 and 24 month old humans) as well as age- and rearing-matched and viral mimic controls, that over their first 2 years of life will undergo a series of detailed assessments including validated tests of soci- oemotional behavior and cognition, structural and functional brain imaging, brain histology, stereology and single cell and bulk cell transcriptomics. Our results may have important public health implications for children living in ZIKV-endemic/epidemic areas as well as for travelers to these regions.",,2025,EMORY UNIVERSITY,736227,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P22059,3R01NS120182-03S1,Neurodevelopment after postnatal Zika virus infection in infant macaques,"PROJECT SUMMARY / ABSTRACT Intense research has focused on the neurologic effects of prenatal Zika virus (ZIKV) infection; however, the consequences of postnatal infection early in life are understudied. Infants exposed to ZIKV in utero but born without microcephaly can develop postnatal microcephaly, neurologic dysfunction, and neurodevelopmental ab- normalities, highlighting the potential of ZIKV to cause ongoing damage after birth. This damage is likely related to the exponential maturation of the brain that occurs during the first 2 years of life, particularly in temporal, prefrontal and parietal regions important for emotional, social and executive functions, including learning, atten- tion and memory. Our group has previously reported that postnatal ZIKV infection causes abnormalities in brain structure, function, and behavior in a pilot study of infant rhesus macaques (RMs) infected postnatally. Here, we propose to extend the scope and duration our prior pilot study and generate novel data regarding the impact of postnatal ZIKV infection on the developing brain. The Objective of this application is to bring new mechanistic insights into postnatal ZIKV infection to address the existing knowledge gap regarding outcomes and host-virus interactions. We will use our postnatal ZIKV-RM model to interrogate the neurobehavioral impact of ZIKV infection at different stages of postnatal brain develop- ment, with approaches that span from single cells to whole animal. This model of postnatal ZIKV exposure allows us to generate key data on the mechanisms by which ZIKV and/or the immune response to infection leads to cellular changes that ultimately result in aberrant postnatal development of limbic structures and behavioral def- icits later in life. We hypothesize that 1) ZIKV and/or the immune response to infection disproportionately affects limbic structures in the postnatally developing brain; 2) cellular changes in these limbic structures lead to aberrant neurodevelopment and abnormal behaviors; and 3) there may be a period of vulnerability to ZIKV during post- natal brain development. We will test our hypotheses in these Specific Aims: 1) Determine the spectrum of abnormal behavior and cognition following ZIKV infection of infant RMs at different stages of brain development; 2) Identify developmental trajectories of brain structure and function following postnatal ZIKV infection of infant RMs at different stages of brain development; and 3) Define the neurodevelopmental pathways and cell types impacted by postnatal ZIKV infection. This work will include RM infants infected with ZIKV at 1 or 6 months of age (equivalent to 4 and 24 month old humans) as well as age- and rearing-matched and viral mimic controls, that over their first 2 years of life will undergo a series of detailed assessments including validated tests of soci- oemotional behavior and cognition, structural and functional brain imaging, brain histology, stereology and single cell and bulk cell transcriptomics. Our results may have important public health implications for children living in ZIKV-endemic/epidemic areas as well as for travelers to these regions.",,2025,EMORY UNIVERSITY,171939,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P22060,1R15AI178654-01,A novel live-attenuated Zika vaccine with a modified 5'UTR,"Summary Zika virus (ZIKV) is a mosquito-transmitted flavivirus that has caused devastating congenital Zika syndromes (CZS), including microcephaly, congenital malformation, and fetal demise in human newborns in the 2015 - 2016 epidemics. In addition, ZIKV infection can cause Guillain-Barré syndrome (GBS) and meningoencephalitis in adults. Currently, ZIKV pathogenesis is incompletely understood, and there is no approved therapeutic or vaccine available. Although the number of human Zika cases has dropped since 2017, ZIKV will likely become endemic, and a vaccine that can prevent CZS and adult Zika diseases remains urgently needed to prepare for future outbreaks. Our research group recently developed a new live-attenuated ZIKV strain (named Z7) by inserting a 50-RNA-nucleotides (nt) hairpin into the 5’ untranslated region (UTR) of a pre-epidemic ZIKV Cambodian strain, FSS13025, which is attenuated in neurovirulence, immune antagonism, and mosquito infectivity compared with the American epidemic isolates. Our preliminary data demonstrate that Z7 replicates efficiently and produces high titers in Vero cells without causing apparent cytopathic effects (CPE) or losing the insert sequence even after ten consecutive passages. Interestingly, we identified a mutation S1417A in NS2B protein in Z7 after the 7th passage, indicating Z7 may have adapted a fitness mutation through the passaging. Importantly, Z7 induces sterilizing immunity that completely prevents viremia after a challenge with a high dose of an American epidemic strain (PRVABC59) in mice. These results suggest that modification of ZIKV 5’UTR is a novel strategy to develop live-attenuated vaccine candidates for ZIKV and potentially for other flaviviruses. In this application, we will first characterize Z7-induced humoral and cell-mediated immunity in a mouse model (Specific Aim 1), and then evaluate the safety features of Z7 in mice (Specific Aim 2). In Specific Aim 3, we will determine the mechanisms of action of Z7 attenuation. We believe that this project is highly significant because it will characterize the immunity and safety of a novel live-attenuated ZIKV vaccine candidate, Z7, which was developed for the first time by introducing a hairpin loop into a viral 5’ UTR. In addition, this R15 project will also provide a valuable and unique training opportunity to both undergraduate and graduate students at the University of Southern Mississippi.",,2026,UNIVERSITY OF SOUTHERN MISSISSIPPI,444000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P22061,5R01GM139823-03,How flaviviruses hijack a host transmembrane protein chaperone to promote viral infection,"Dengue virus (DENV) infection is the most common arboviral disease globally, with up to 400 million infections and 25,000 deaths annually. The related flavivirus Zika virus (ZIKV) has also spread rapidly across the tropics and subtropics, and outbreaks of both DENV and ZIKV infection have now reached the continental United States. There are currently no effective antiviral agents against either virus, no DENV vaccine approved for use in the United States, and no ZIKV vaccine. Our long-term goal is to comprehensively identify and characterize the cellular pathways required for flavivirus infection, as these may represent novel targets for antiviral treatment. We and others have identified the host Endoplasmic Reticulum Membrane Protein Complex (EMC) as required for infection by multiple flaviviruses, including DENV and ZIKV. The EMC appears to function as a molecular chaperone, promoting the biogenesis of multipass membrane proteins in the endoplasmic reticulum. However, how the EMC supports flavivirus infection is unknown. Strikingly, our published findings reveal that during infection, the EMC is required by flavivirus replication by promoting the biogenesis of flavivirus NS4A and NS4B at an early post-translational step. Both proteins are non-structural multipass transmembrane proteins essential for viral replication. The objective of this proposal is to define how the EMC supports DENV and ZIKV replication. Our central hypothesis, based on strong preliminary data, is that the EMC functions as a molecular chaperone for the proper biogenesis of select flavivirus-encoded multipass transmembrane proteins. This proposal leverages the complementary strengths of an investigator with extensive experience in flavivirus-host biology (Tai), and another in ER-quality control mechanisms hijacked during viral infection (Tsai). The specific aims of the project are to (1) Define and validate the viral determinants of EMC dependence; (2) Determine the specific role of the EMC in flaviviral replication; and (3) Characterize DENV and ZIKV mutants that bypass EMC dependency. Successful completion of this project will illuminate the mechanism by which the EMC supports flavivirus infection, thereby providing insights into a novel vulnerability shared by these medically important viruses. It will also increase our understanding of other viruses that require the EMC.",,2025,UNIVERSITY OF MICHIGAN AT ANN ARBOR,356140,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22062,5R01AI153433-04,A Novel Strategy for Generating Safe and Effective Flavivirus Vaccines,"The recent emergence and devastating impact of Zika virus (ZIKV) clearly demonstrates that arboviral emergence continues to defy accurate prediction and exposes our inability to rapidly respond to and control outbreaks. The medical and veterinary importance of emerging flaviviruses is significantly exacerbated by the absence of available vaccines, therapeutics, and reliable control measures. Vaccination remains the most reliable strategy for outbreak prevention and control, but vaccine development intrinsically involves trade-offs between safety and immunogenicity. This study will develop a platform to overcome these trade-offs by combining the safety advantages of non-replicating platforms with the rapid and long-lived immunogenicity of a live-attenuated vaccine. We have developed a unique chimeric virus platform based on a novel insect-specific flavivirus (ISFV), Aripo virus (ARPV). Preliminary data shows ARPV’s host restriction is noticeably later in the replication cycle than described for other ISFVs and is capable of entering vertebrate cells and developing a robust immune response in the absence of genomic replication. An ARPV/ZIKV chimera was developed to test our hypothesis that ARPV/ZIKV vaccination produces a rapid and robust innate, humoral, and cell-mediated immune response that elicits sterilizing immunity against subsequent ZIKV challenge. Preliminary studies show a single dose of ARPV/ZIKV produces a robust adaptive ZIKV-specific immune response that completely protects mice from viremia, weight loss, and mortality, while demonstrating exceptional safety in vivo. This platform is superior because of the increased safety of the chimera by virtue of its fundamental replication defect in vertebrate cells, increased immunogenicity due to a lack of inactivation requirements, and efficient genome delivery to target cells. This innovative and essential R01 aims to evaluate the safety profile, protective efficacy and mechanisms underlying the immunogenicity of ARPV/ZIKV vaccination via three aims: 1. Determine the efficacy of ARPV/ZIKV immunization for preventing ZIKV-induced disease in murine and rhesus macaque models. 2. Elucidate the correlates underlying vaccine-induced protection from ZIKV-induced disease in ARPV/ZIKV vaccinated murine models. 3. Evaluate the safety profile of this vaccine candidate in vitro and in vivo, and elucidate the mechanism underlying its immunogenicity. This study will generate a safe, efficacious, single-dose ZIKV vaccine that will be ideally suited to affordably control explosive outbreaks, which typically affect resource-limited regions. Our platform’s antigenic superiority will result in enhanced efficacy, effectively combining the safety of replication-defective virus-like particles or nucleic acid vaccines with the antigenic superiority, and rapid, long-lived immunogenicity of live-attenuated vaccines. This platform can also be readily translated to other flaviviruses of human or veterinary importance.",,2025,VIRGINIA POLYTECHNIC INST AND ST UNIV,403588,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22063,1R01AI170857-01A1,Molecular mechanisms linking viral replication and neuropathogenesis,"PROJECT SUMMARY/ABSTRACT Viruses that infect the developing brain, including Zika virus (ZIKV), cytomegalovirus, and rubella virus cause major birth defects. Microcephaly is one such birth defect, in which head and brain size are severely reduced, and is often accompanied by intellectual disability. This virally-inflicted neurological disease, or viral neuropathogenesis, can be caused by multiple mechanisms. One recently identified way ZIKV non-structural protein 4A (NS4A) causes microcephaly is by disrupting the human ANKLE2 protein. Interestingly, individuals with mutations in the gene encoding ANKLE2 suffer from microcephaly. ANKLE2 is conserved from worms to humans, and is essential for coordinating cell division during brain development. ANKLE2 derives this function in cell division and development by mediating protein interactions. NS4A physically interacts with ANKLE2 and disrupts brain development in an ANKLE2-dependent manner in a fruit fly model of brain development. ANKLE2 also promotes ZIKV replication. Taken together, these studies show that in the process of coopting a host protein for replication, ZIKV dysregulates an important developmental pathway. Thus, the NS4A-ANKLE2 protein interaction represents an important model to study viral neuropathogenesis and how it is connected to viral replication and hereditary disorders at the molecular level. The long-term goal of this work is to decipher how virus-host protein interactions impact virus replication and pathogenesis, as these discoveries will fuel therapeutic target identification and drug development. The objective of this proposal is to dissect the mechanisms by which the protein interaction between ZIKV NS4A and human ANKLE2 promote ZIKV replication and inhibit brain development. To accomplish this objective, we will test the central hypothesis that ANKLE2 promotes viral replication through its interaction with NS4A and by recruiting other host factors involved in ZIKV replication to sites of replication, and this disrupts physiological ANKLE2 protein interactions required for brain development. The following specific aims will test this hypothesis: Aim 1: Dissect the impact of the NS4A-ANKLE2 protein interaction in ZIKV replication and pathogenesis. Aim 2: Unravel the molecular function of ANKLE2 in ZIKV replication and pathogenesis. When completed, this work will delineate how a single virus-host protein interaction rewires a developmental pathway to facilitate virus replication and inflict neurological disease at the molecular level. This will reveal detailed biochemical insight into a virus-host protein interaction with amino acid-level resolution, new host factors that play a role in ZIKV replication, and previously unknown proteins key to brain development and disrupted in other hereditary developmental disorders. In the long term, the methods established here could be employed to uncover the molecular mechanisms behind other diseases with viral and hereditary etiologies.",,2028,UNIVERSITY OF CALIFORNIA AT DAVIS,391009,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P22064,5R00DE028573-05,Molecular regulatory mechanism of Zika virus-induced intracranial calcifications,"Project Summary/Abstract: The number of vector-borne disease cases in the US has tripled over the past decade and these pathogens including mosquito-borne Zika virus (ZIKV) remain an apparent threat to general public health. The ZIKV outbreaks in the Americas and Southeast Asia is a major global health concern, largely due to the association with fetal craniofacial abnormalities and malformations, resulting from prenatal infection. Although ZIKV infection during pregnancy is casually associated with microcephaly, it is important to note that intracranial calcification is the most frequent abnormality present in ZIKV-positive babies. In fact, Magnetic Resonance Imaging study of Brazilian large ZIKV-positive baby cohort reported the intracranial calcifications as the most common clinical observations. While calcification occurs in soft tissues, the abnormal deposition of calcium in brain not only severely affects motor function, speech ability, and vision, but also causes seizures. Despite the growing clinical evidences of ZIKV-induced calcifications and their potential dire outcomes, however, the etiology and molecular mechanisms of ZIKV-induced brain calcification remain elusive. My preliminary observations in ZIKV human fetal brain specimens showed that high level of calcium deposits was localized with virus-infected perivascular cells. Intriguingly, ZIKV-infection of brain perivascular and osteogenic precursor cells robustly induced calcifications in vitro. Surprisingly, the induction of calcification was lineage-specific to the Asian ZIKV strains, but not to the African ZIKV strains. African ZIKV strains rapidly replicated, inducing cell death, while Asian ZIKV strains persistently replicated, leading to aberrant calcium deposition. Surprisingly, ZIKV expression library screen showed that NS3 protease was sufficient to induce calcification. Based on these preliminary data, I hypothesize that ZIKV targets specific host brain perivascular cells and utilizes NS3 protease to induce intracranial calcifications, which ultimately contributes to virus-associated congenital abnormality. Herein, I seek to address the following questions: (i) which host cells are targeted for ZIKV-induced calcifications, and (ii and iii) which and how ZIKV NS3 protease triggers abnormal calcification during infection. This proposal is highly innovative and translational, and potentially shed new insights to ZIKV-induced intracranial calcification that is the most frequent abnormality present in virus-infected babies.",,2025,CLEVELAND CLINIC LERNER COM-CWRU,248999,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2022 +P22065,5R01NS125778-02,Role of microglia in neural infection,"ABSTRACT Zika virus (ZIKV) infection is associated with congenital ZIKV syndrome (CZS), including various brain anomalies and microcephaly. Our recent studies suggested that yolk sac (YS)-derived microglia (primary immune cells in the brain) and Peli1 (an E3 ubiquitin ligase) are involved in ZIKV infection and its associated CZS. However, it is unknown whether and how Peli1 contributes to the YS-microglia-mediated spread of ZIKV into brain, whether viral infection affects the normal function of microglia, and how such effects influence neural differentiation. Based on preliminary data, we hypothesize that Peli1 plays a critical role in fetal brain ZIKV infection via promoting YS-microglia-mediated ZIKV dissemination into fetal brain and via altering microglial function to affect neural differentiation. This hypothesis will be tested by two specific aims: 1) to determine how Peli1 promotes ZIKV infection of YS-microglia and virus dissemination from microglia to neural stem cells in fetal brains; and 2) to determine how Peli1 mediates microglial activation and alters neural differentiation after ZIKV infection. This integrative study employs biochemical and genetic manipulations in both in vivo animal models and in vitro mouse and human cell platforms. The outcomes will be evaluated by molecular, cellular, and neuroanatomical analyses. Understanding the molecular mechanisms underlying the role of microglia in ZIKV-related brain infection may lead to identification of new targets for prevention and treatment of ZIKV and other virus-mediated congenital neural infections.",,2026,UNIVERSITY OF TEXAS MED BR GALVESTON,516055,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P22066,5R01EY032149-03,Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection,"PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pathology, including loss of foveal reflex and macular pigment mottling, chorioretinal scarring, and macular atrophy. ZIKV has become endemic and local transmissions in the USA have been reported previously. The long-term effects of structural damage on vision, as well as the pathogenic processes of congenital ZIKV eye diseases are beginning to be understood. The signaling pathways governing normal eye development, which are dysregulated during ZIKV infection, are not well characterized. We recently carried out a series of experiments by establishing a ZIKV infectious ocular cell culture system and mouse models to understand the structural and molecular perturbations. For successful replication, viruses have evolved various strategies to evade innate immune response as well as to enhance the availability of cellular metabolites required to meet the heightened energy demand for viral genome synthesis. We found that the AMPKα, a cellular master energy sensor, is activated in the ZIKV-infected retinal cells. Moreover, pharmacological activation of AMPK resulted in attenuated ZIKV replication. Another interesting finding is that the YAP/TAZ factors in the tumor suppressor Hippo/SWH signaling pathway were induced early on, but degraded at later stage of ZIKV infection in RPE cells. Silencing YAP/TAZ resulted in reduced ZIKV replication. Since the energy sensor AMPK and Hippo signaling pathways control key cellular processes, including host antiviral responses, it is critical to understand the fundamental mechanism of these two pathways deregulation. We hypothesize that ZIKV modulates AMPK and Hippo signaling pathways in ocular cells to 1) increase intracellular metabolic resources, and 2) inhibit TBK1 to antagonize antiviral defense. These molecular changes can be orchestrated through viral coded factors resulting in the pathogenesis of ocular cell injury. The following specific aims will be investigated. Aim 1 focuses on systematically evaluating the role of AMPK- Hippo signaling on regulating antiviral response to ZIKV infection in RPE cells. The cross talk between these pathways will be investigated at the YAP/TAZ level. Pharmacological activation/inhibition, and gene knockout approaches in RPE cells will be carried out. Aim 2 is designed to elucidate the effect of ZIKV on Hippo and AMPK signaling pathways during retinal development. Human iPSC-derived 3D-retinal cup organoids will be used to investigate the link between retinal development and ZIKV-mediated deregulation of these key pathways. The ZIKV-encoded virulence factors regulating these pathways will be characterized. Aim 3 is to determine the effect of RPE-specific ablation of AMPK, TBK1, and Hippo signaling on the pathogenesis of ZIKV-induced chorioretinal atrophy in mice. This proposed study would yield novel insights into the pathogenesis of ZIKV in ocular diseases and identification of potential therapeutic targets.",,2024,UNIVERSITY OF CALIFORNIA LOS ANGELES,520349,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2021 +P22067,5R01AI153724-02,Development of a vaccination platform for emerging flavivirus infections,"Project Summary: The Flavivirus genus (referred to as flaviviruses) consists of numerous emerging and re-emerging global pathogens of critical human significance. Endemic and emerging flaviviruses like dengue virus (DENV), Powassan virus (POWV), Zika virus (ZIKV), West Nile virus, Japanese Encephalitis virus and Yellow fever virus continue to spread and cause significant human disease. We have used RNA structural data from a conserved 3’ untranslated region (UTR) pseudoknot called xrRNA1 to develop an attenuation approach in a highly conserved structural region of the flavivirus 3’UTR for vaccine development. This approach allows us to 1) swap out flavivirus structural genes in our clone to rapidly develop chimeric, attenuated flavivirus vaccines for mosquito-borne flaviviruses and 2) provides a conserved site for attenuation for tick-borne flaviviruses like POWV. Based on our preliminary data, we hypothesize that xrRNA1-mutant, attenuated flavivirus vaccines will be safe, immunogenic, and provide protection from challenge in murine models of flavivirus disease. The objective of the proposed studies is to complete pre-clinical development of the attenuated flavivirus vaccine approaches. We will complete our proposed work in three aims that will evaluate immunologic and virologic outcomes following virus challenge after vaccination with candidate ZIKV vaccine (Aim 1), DENV vaccine (Aim 2), and POWV vaccine (Aim 3). We have recently published our data showing attenuation and immunogenicity of mutant xrRNA1 ZIKV (X1) in pregnant and non-pregnant mice. In this proposal, we will first evaluate the efficacy of ZIKV X1 vaccine in pregnant and non-pregnant mice challenged with ZIKV and DENV. These studies will allow us to evaluate ZIKV vaccine efficacy during pregnancy and evaluate the role of ZIKV vaccination in DENV disease enhancement. Next, we will use the attenuated, ZIKV vaccine platform developed in our laboratory using xrRNA1 structural data, insert chimeric pre-membrane and envelope structural genes from DENV1-4 and evaluate the attenuation, immunogenicity and efficacy of monovalent and quadrivalent DENV1-4 vaccine candidates. Given the complexity of DENV infection, we will evaluate disease enhancement and immunodominance in our quadrivalent vaccines along with efficacy. Third, we will expand our attenuation strategy in the X1 structure to tick-borne flaviviruses by utilizing our recently defined secondary structure of the POWV 3’UTR. Using POWV mutant vaccine candidates with targeted mutations in the X1 structure, we will characterize attenuation, immunogenicity, and efficacy of a POWV vaccine approach in a murine model of disease. The proposed studies will begin to translate our structural understanding of xrRNAs in the flavivirus 3’UTR into potential vaccine candidates. Moreover, this project will initiate studies focused on developing a platform for vaccine development for emerging flavivirus infections.",,2023,UNIVERSITY OF COLORADO DENVER,436523,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2021 +P22068,1R21AI178672-01,Functional Role of Pseudouridine on Zika Virus Gene Expression,"Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus, that during the 2015-2016 outbreak in the Americas was associated with severe and devastating developmental abnormalities, including microcephaly, in babies born from infected women. The single-stranded positive-sense RNA genome of ZIKV directs translation of viral proteins, functions as a template for replication of the genome and is packaged into new virus particles. These functions are in part regulated by specific RNA structures within the untranslated regions of the RNA, and via interactions with viral and cellular proteins. More recently RNA modifications have been shown to significantly affect the virus infectious cycle. Although more than 170 different RNA modifications are known to decorate natural RNAs, only N6-methyladenosine has been reported to affect ZIKV gene expression. The role of other RNA modifications on ZIKV RNA is presently unknown. Using biotinylated antisense oligonucleotides to affinity isolate virus RNA from cells and virions, and mass spectrometry to identify RNA modifications, we discovered that more than 30 different RNA modifications are present on ZIKV RNA. In this application we focus on pseudouridine (Y), an abundant but understudied RNA modification. The incorporation of Y on cellular RNAs affects the folding, stability, and translation of RNA, and RNA-RNA and RNA-protein interactions. We propose that Y on the ZIKV RNA genome promotes virus translation and replication. In this application we propose using a next generation sequencing approach combined with chemical modification of pseudouridine to identify specific Y sites on ZIKV genome (Aim 1). Next, we will undertake RNAi depletion and overexpression of cellular pseudouridine synthase proteins to identify the host enzymes responsible for installing pseudouridine on ZIKV RNA (Aim 2). Last, we will use mutagenesis and modulation of the pseudouridine synthase enzymes to elucidate if pseudouridine regulates ZIKV translation and/or replication (Aim 3). Moreover, these studies will be undertaken in the context of virus infection in mammalian and mosquito cells, two hosts biologically relevant to the virus life cycle, which could inform the role of RNA modifications in virus transmission and host adaptation. We expect that this research will advance our knowledge of RNA modifications which have been shown to be novel and important regulators of viral gene expression and improve our understanding of the molecular biology of ZIKV. This research will therefore provide critical information on a virus with significant impacts on human health and that currently lacks therapeutic options.",,2025,STATE UNIVERSITY OF NEW YORK AT ALBANY,228026,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P22069,5K08AI150996-04,Innate Immunity of Zika Virus Infection In Human Neural Progenitors,"PROJECT SUMMARY / ABSTRACT The 2016 outbreak of Zika virus (ZIKV) in the Americas demonstrated how quickly and dramatically a mosquito-borne viral infection can affect human life. Like related flavivirus family members such as West Nile virus, ZIKV can invade and infect the central nervous system (CNS), but is unique in causing in utero infection which leads to developmental abnormalities including microcephaly. ZIKV seems to have a predilection for infecting neural progenitor cells (NPCs) and persists for months in the fetal CNS after in utero infection, which suggests an ineffective immune control of the virus. We hypothesize that impaired innate immunity in neural progenitor cells underlies increased susceptibility to infection by ZIKV and contributes to microcephaly. The innate immune system includes pattern recognition receptors (PRRs) that detect pathogens and signal through effector molecules including interferon (IFN), which drives the expression of hundreds of antiviral interferon-stimulated genes (ISGs). Using induced neural progenitor cells (iNPCs) as a model for fetal CNS development, we have identified key innate immune signals that are attenuated in neural progenitors compared to mature neurons and glia: the expression levels of retinoic acid-inducible gene I (RIG-I, a PRR that detects viral RNA); and the IFN-driven upregulation of two ISGs (IFIT1 and IFITM1). We now propose to extend these findings as follows: (1) we will define the developmental changes in expression and function of PRRs during neural differentiation using the iNPC system and an established embryonic stem cell line as a control; (2) we will use CRISPR knockout or overexpression of RIG-I in bulk iNPCs and in a cerebral organoid model to test whether insufficient RIG-I signaling underlies iNPC susceptibility to ZIKV infection and microcephaly; (3) we will perform single cell RNA-seq on ZIKV-infected neural progenitors, neurons and glia to identify differentially expressed genes and gene networks, revealing innate immune components that confer susceptibility or resistance to ZIKV; and (4) using CRISPR knockout or overexpression of IFIT1 and IFITM1 we will test the role of these proteins in limiting ZIKV infection in progenitors and cerebral organoids. These experiments will define key innate immune proteins that influence susceptibility or resistance to ZIKV, identifying therapeutic targets to protect the fetal brain during ZIKV infection. Dr. Stokes’ development plan builds on a background in neurosciences with coursework and hands-on training in immunology, neural stem cells, and bioinformatics. The proposal establishes a mentoring committee including faculty in immunology, neurosciences, and infectious disease to provide guidance and career development. A K08 award will allow Dr. Stokes to make maximal use of UW’s extensive scientific resources to achieve scientific independence, advancing his career goal to develop therapeutic interventions that protect neural function from injury during viral encephalitis.",,2025,UNIVERSITY OF WASHINGTON,193911,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Pathogen morphology, shedding & natural history",2020 +P22070,1R21AI177623-01,The mechanism of flaviviral suppression of vitamin A metabolism,"Mosquito-borne viruses, primarily including families of Flaviviridae (dengue, Zika etc.) and Togaviridae (Chikungunya etc.), infect roughly ~400 million people worldwide. By a blood meal, a naïve female mosquito may acquire an infectious agent (e.g., virus) from an infected person, and pass it on to next person. Therefore, the host-seeking and blood-feeding behavior of female mosquitoes is a key determinant of virus circulation in nature. The mammalian body odors contain many volatile chemical compounds that influence mosquitoes’ behaviors. Some of these are well-characterized mosquito attractants. These cues vary from a person to another person, and with the physiological conditions of the same person. However, it remains unknown if mosquito- transmitted viruses can manipulate their host odors to influence mosquito behaviors. In a recent study, we found that dengue (DENV) and Zika (ZIKV) can manipulate their mammalian host skin microbiota to produce a potent mosquito attractant, acetophenone. This was because viral infection significantly increased the abundance of skin Bacillus bacteria, the major producer of acetophenone as a volatile metabolite. DENV/ZIKV downregulated (~25-fold) the expression of a resistin-like bactericidal antimicrobial peptide (AMP), RELMα, in the mouse skin. These results demonstrate that DENV/ZIKV can enhance their host attractiveness to mosquitoes, thus facilitate their transmission. However, how these viruses inhibit RELMα expression is unknown. Constitutive RELMα expression (not any other skin AMPs) requires dietary retinols (a.k.a vitamin A), suggesting that DENV/ZIKV likely intervenes retinol signaling. Retinols are bound by retinol binding protein 4 (RBP4) and transported by a cell surface receptor STRA6, converted into retinaldehydes by retinol dehydrogenase 1 (RDH1), then to retinoic acids by retinaldehyde dehydrogenase 1A (RALDH1A). Retinoic acids bind retinoic acid receptors (RARs), which enter the nucleus and activate gene transcription, including RELMα and RARs. Intriguingly, oral administration of a retinoic acid, isotretinoin, restored normal RELMα expression and skin microbial homeostasis to DENV/ZIKV-infected mice, suggesting that DENV/ZIKV target a step between retinol and retinoic acid. Indeed, our new data showed that DENV/ZIKV replicated productively and suppressed RELMα and RAR expression induced by retinol, but not by retinaldehyde or isotretinoin in mouse primary skin epidermal keratinocytes, the primary epidermal cell type and producer of AMPs. Of note, the Chikungunya virus did not inhibit retinol signaling. Therefore, we hypothesize that DENV/ZIKV interferes with a step between retinol and retinaldehyde of the retinol pathway. To this end, we will pinpoint the step of the retinol pathway targeted by DENV/ZIKV, and identify the viral protein (s) that suppress the retinol pathway. We will address how these flaviviruses suppress the retinol pathway and RELMα expression in the skin. These results could be applicable to other mosquito-borne flaviviruses and lay a foundation for in-depth mechanistic studies.",,2025,UNIVERSITY OF CONNECTICUT SCH OF MED/DNT,207500,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P22071,5R01AI148477-04,Implications of sequential bloodmeals on arbovirus transmission by mosquitoes,"Brackney & Armstrong Abstract: Aedes aegypti is the primary vector for a number of human pathogens, including dengue virus (DENV; Flaviviridae, Flavivirus), Zika virus (ZIKV; Flaviviridae, Flavivirus), chikungunya virus (CHIKV; Togaviridae, Alphavirus) and yellow fever virus (YFV; Flaviviridae, Flavivirus), all of which present a continued threat to human health worldwide. Understanding the endemic and epidemic risk of these arthropod-borne (arbo-) viruses is critical to the success of public health preparedness and intervention. One key entomological parameter informing risk estimates is vector competence (how able a mosquito is to become infected and transmit an arbovirus; VC). Quantifying the competency of local vector populations can help inform the risk that any one pathogen poses to a given community. This is often quantified in the laboratory by exposing populations of local mosquitoes to an infectious bloodmeal and harvesting tissues at set time-points post infection. While informative, this approach often fails to consider the biology and behavior of the vector mosquito. For example, it is known that wild Ae. aegypti mosquitoes will imbibe several bloodmeals over the course of a traditional laboratory-based vector competence study (e.g. bloodmeal every two to three days). To address these shortcomings, we recently began examining the effects that multiple blood feeding episodes have on the competency of Ae. aegypti mosquitoes for ZIKV. Our preliminary findings reveal that providing a second non-infectious bloodmeal to ZIKV infected Ae. aegypti mosquitoes enhances viral escape from the midgut and significantly shortens the duration between mosquito acquisition of ZIKV to transmission. In this application we will examine the effects that multiple bloodfeeding episodes have on arbovirus infection of and transmission by vector mosquitoes. Specifically, we will be 1) testing this phenomenon in other virus-vector pairings, 2) evaluating the role of the midgut basal lamina in mediating the double-feed phenotype and 3) determining if similar processes are mediating the ability of arboviruses to infect ovarian tissue and be transmitted vertically.",,2025,CONNECTICUT AGRICULTURAL EXPERIMENT STA,298272,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22072,5R01NS117149-03,Leveraging Zika virus and the immune system to treat glioblastoma,"PROJECT SUMMARY Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2 years. Despite aggressive therapy, most GBMs reappear within 6 months. A major reason for this outcome is because GBM stem cells (GSCs) are resistant to existing therapies. Currently, no treatment consistently kills these highly resistant cells. However, the Zika virus epidemic has provided us with a new approach to eradicate GSCs. ZIKV targets normal stem cells in the developing fetal brain, yet has minimal effects on differentiated neurons or the adult brain. Since GSCs share properties with neural stem cells, we investigated whether the natural honing and lytic activity of ZIKV could be harnessed to target and kill GSCs. We published the first use of ZIKV to kill GSCs. We showed that ZIKV kills GSCs in tumors removed from patients, with minimal impact on non-GSC tumor cells, called differentiated GBM cells. Importantly, normal human brain cells were not affected by ZIKV. After intracranial treatment with ZIKV, mice harboring gliomas survived more than twice as long as untreated mice and, in some cases, treated mice were long-term survivors. In addition to the resistance of GBM stem cell to chemoradiation, GBM is the hallmark example of an immunotherapy-resistant tumor. Importantly, we found that in vivo, ZIKV treatment reduces tumor size and extends survival beyond that expected for only anti-GSC effects. This suggested that ZIKV killing of GSCs may trigger an immune response against the remainder of the tumor. In more recent studies, we have found that CD8+ T cells are required for the efficacy of ZIKV as an oncolytic therapy in vivo. Our central hypothesis is that ZIKV elicits an anti-tumor immune response that could be made even more effective by combining it with existing immunotherapies. Aim 1 will determine how CD8+ T cells promote tumor clearance after ZIKV and Aim 2 will determine whether ZIKV can be combined with immunotherapy or standard-of-care for GBM to improve outcomes. Our long-term goal is to develop a new treatment for GBM by leveraging the immune system response to ZIKV.",,2025,WASHINGTON UNIVERSITY,456534,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2020 +P22073,1R01AI168169-01A1,Defining the molecular interactions required for flavivirus genome packaging and virus assembly,"Arthropod-borne flaviviruses such as Zika, dengue, West Nile, and Powassan viruses cause hemorrhagic fever, congenital diseases, and fatal encephalitis in humans. Zika virus (ZIKV) has the unique ability of human-to- human transmission vertically from mother to fetus and horizontally through sexual contact. In the current proposal, we identify a previously undefined cellular mechanism of ZIKV assembly in live placental cells and aim to characterize the underlying mechanisms of formation and intracellular trafficking of modified membrane structures that facilitate maturation and release. We present preliminary data supporting our novel hypothesis that aptamer tagging of genomic RNA and using fluorescent-protein tagged capsid and nonstructural protein 2A (NS2A), we can visualize and understand mechanisms of virus assembly and virus-host interactions in live cells. By creating a library of mutant ZIKV for live imaging, we identified critical amino acids in capsid protein and NS2A coordinating virus assembly. Using tagged NS2A ZIKV, we present the first viral and host interactome of NS2A from infected cells that have thus far evaded mass spectrometry approaches and identified NS2A-interacting host proteins associated with microcephaly, RNA trafficking, and ER modifications. Using confocal and transmission electron microscopy, we found that ZIKV NS4B modifies the canonical secretory pathway and mediates homotypic fusion of vesicles originating from the ER exit sites forming large perinuclear structures near the Golgi apparatus. Building on our preliminary data and using unique ZIKV infectious clones and tools we have so far developed; we propose a rigorous set of experiments designed to test our hypothesis that flaviviruses modify the ER and host secretory pathways to form large vesicular structures that facilitate assembly and intracellular trafficking. First, using a library of labeled viral RNA and protein constructs with confocal imaging, we will confirm the fate of viral RNA, identify the specific regions of C, NS2A, and RNA that may participate in virus budding and interaction with viral and host proteins, and evaluate whether RNA interacting proteins facilitate assembly (Aim 1). Second, using an advanced affinity purification-mass spectrometry and siRNA and CRISPR knockdown approach, we will determine the genomic pathways in the ER that are key for virus production and cellular membrane modification (Aim 2). And third, we will investigate the ER exit of assembled viruses, NS4B mediated large vesicle formation, and vesicular retrograde transport via microtubules and determine its effect on the dynamics of ZIKV maturation (Aim 3). Our findings will establish a previously undescribed and essential cellular mechanism for the assembly of ZIKV and identify critical targets for intervention in ZIKV infections and other related viruses, addressing a significant global public health need and contributing to the NIAID mission to understand, treat, and prevent infectious diseases. This knowledge can generate new ER-associated targets for therapeutic intervention to mitigate viral transmission at the maternal-fetal interface.",,2028,"PENNSYLVANIA STATE UNIVERSITY, THE",385887,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P22074,5F31AI154695-03,Effect of an Fc Gamma Receptor Polymorphism on Antibody-Dependent Enhancement of Zika Virus Infection,"PROJECT SUMMARY Antibody-dependent enhancement (ADE) is a phenomenon by which antibodies raised in response to a primary infection cross-react to a similar pathogen during a subsequent infection, resulting in increased viral load and severity of disease. ADE of Zika virus (ZIKV) infection by preexisting DENV antibodies has been hypothesized to play a role in the severe adverse pregnancy outcomes observed following congenital ZIKV infection. ADE is mediated by interactions between virus-bound IgG antibodies and Fc gamma receptors (FcRs) on host cells. In humans, a nonsynonymous single nucleotide polymorphism (SNP) in FCGR2A, rs1801274, results in an amino acid change at site 131 from arginine (Arg131) to histidine (His131) in the IgG-binding region of FcRIIA. Previous work in vitro has shown that cells expressing the His131 receptor variant bind human IgG1 and IgG2 with significantly higher affinity than those expressing the Arg131 receptor variant. We hypothesize that individuals homozygous for the high affinity His131 allele will be at greater risk for ADE of viral infection than individuals homozygous for the low affinity Arg131 allele. In this application, we will assess the effect of this SNP on ADE of ZIKV using cell lines derived from K562 cells that are homozygous for the Arg131 or His131 allele and primary human monocytes that will be stratified by genotype (Aim 1). We have also generated IgG subclass switch variants of a flavivirus-reactive monoclonal antibody that we will use to assess the role of each IgG subclass in mediating ADE of ZIKV through the different FcRIIA variants using His131 and Arg131 homozygous K562 cell lines, primary human monocytes, and Hofbauer cells isolated from full term human placentas (Aim 2). A comprehensive understanding of host genetic factors that affect susceptibility to ADE, including those described in this proposal, may help to identify populations at increased risk of developing severe disease as a result of ZIKV infection, particularly among pregnant women. The proposed project provides an excellent opportunity for training that encapsulates traditional virology and immunology techniques, professional development, and mentorship that will support the applicant’s growth as an independent academic scientist.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,46094,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2021 +P22075,5R01AI146049-03,Anchimerically Activatable Anti-Zika/Dengue ProTides,"Arboviruses such as, Dengue (DENV) and Zika (ZIKV), have been associated with several global epidemics. DENV infections can result in a mild fever to potentially fatal dengue shock syndrome, dengue hemorrhagic fever and death, while ZIKV infections can result in congenital microcephaly and the development of autoimmune diseases. Initial clinical manifestation of DENV and ZIKV disease are similar and co-infections have been reported. Most challenging, DENV and ZIKV are known to co-circulate, increasing the probability of co-infections, and thus the potential for severe disease. Consequently, since there is no effective vaccine or form of treatment for either virus, the development of anti-ZIKV and anti-DENV therapeutics is an urgent unmet medical need. Over the past decade prodrugs of nucleotides, referred to as ProTides, have been found to have potent antiviral activity. The anti-hepatitis C virus (HCV) drug sofosbuvir (FDA approved 2013) is the most notable ProTide success, since its use in combination therapy can clear Hepatis C virus infections. Recently, a similar ProTide, remdesivir, has been approved by the FDA, Japan, the European Union an Australia for the treatment of severe SARs-CoV-2 infections by intravenous injection. Carboxyesterase-anhydride-HINT1 (CAH) ProTides, such as sofosbuvir and remdesivir, utilize a four step activation process based on initial esterase hydrolysis, carboxylic acid nucleophilic attack at the phosphorous and release of phenol, followed by mixed anhydride chemical hydrolysis, and finally phosphoramidate hydrolysis by hHINT1. Unfortunately, although they can be dosed intravenously, due to high first pass metabolism, CAH-Protides are limited in their use as oral drugs to viral hepatitis. Furthermore, due to the high carboxyesterase activity of rodent plasma, it has been difficult to carry out pre-clinical studies with rodents and translationally relevant dosages of CAH-ProTides. To address the inherent issues surrounding current ProTide approaches, our group has designed an alternative ProTide approach, we refer to as anchimerically HINT1 activated proTides (AHA-ProTides). Our laboratory has demonstrated that AHA-proTides can be designed that are stable, orally bioavailable, cell permeable and dependent on HINT phosphoramidate hydrolysis. Recently, we have also demonstrated that AHA proTides can be prepared with enhanced potency against DENV and ZIKV. Consequently, we propose to the design and develop anti-DENV and anti-ZIKV AHA ProTides that can serve as advanced lead compounds for the potential treatment of both DENV and ZIKV disease.",,2026,UNIVERSITY OF MINNESOTA,568956,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22076,1R21AI175733-01,Development of MS2045 for inhibition of Zika methyltransferase,"Project Summary The Zika virus (ZIKV) is a member of the Flavivirus genus that includes other arthropod-borne human pathogens such as dengue virus and West Nile virus, among others. ZIKV’s link to microcephaly in newborn infants and the Guillan-Barré syndrome in adults has invigorated measures to develop a vaccine, as well as efforts to develop antivirals based on targeting enzymatic activities central to the life cycle and survival of ZIKV. One such enzymatic activity is encoded by the methyltransferase (MTase) domain, located at the N-terminus of the nonstructural protein NS5. Taking a structure informed approach, we have succeeded in identifying a novel “lead-like” compound (MS2045) for the inhibition of ZIKV’s NS5 MTase activity and for blocking its replication. MS2045 provides a basis for further chemistry and the development of even more potent inhibitors. In aim 1, we will a) design MS2045 analogs with the capacity to establish specific interactions with unique amino acids of ZIKV MTase as a means to provide additional selectivity against the human RNA 5’-cap MTases; b) chemically synthesize these analogs and produce them to a purity of 95% for in vitro and cell-based assays, and for structural studies. In aim 2, we will a) perform biophysical assays to assess the ability of these analogs to selectively bind the ZIKV NS5-MTase as compared to the human RNA 5’-cap MTases and test their ability to inhibit RNA methylation; b) test these analogs in viral cell-based assays to assess their efficacy in blocking viral replication; c) determine structures ZIKV NS5-Mtase with select analogs for additional, iterative rounds of structure activity relationships (SARs). Collectively, these studies will help to identify analogs of MS2045 that can be potentially developed into potent and selective inhibitors of NS5-MTase from ZIKV (and other pathogenic flaviviruses)",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,253500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P22077,5R01AI155735-03,Multiplexed Detection of Mosquito-Borne Viruses at the Point-of-Care,"Project Summary Dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), and Mayaro virus (MAYV) are all mosquito-borne RNA viruses. They are public health concerns because (1) DENV and CHIKV cause hundreds of millions of infections each year, with significant burdens in affected areas, (2) the outbreak of ZIKV in Brazil in 2015/2016 caused anxieties to general population due to its association with microcephaly of newborns, and (3) MAYV emerged in Central and Southern America recently and has the potential for epidemic spread. Because these virus infections have virtually identical clinical presentation and they often circulate concurrently, it is important to have a point-of-care (POC) testing platform to accurately identify virus infection for clinical management of patients, including different complications from these viruses. According to the Centers for Disease Control and Prevention (CDC), the current methods authorized for assessing DENV, ZIKV, and CHIKV infections include reverse transcription polymerase chain reaction (RT- PCR) assay and enzyme-linked immunosorbent assay (ELISA). However, these assays are carried out in laboratories, not at POC in a clinic or in an infected field. It is also important to note that virus infection can cause asymptomatic infections, up to 80% of ZIKV patients, 50% of DENV patients, and 28% of CHIKV patients, respectively. As a result, POC testing in the field will be more valuable for screening asymptomatic patients and monitoring possible virus transmission than a laboratory test because only symptomatic patients go to hospitals or clinics for seeking medical help or to be screened. To address the need, we propose to develop a POC diagnostic platform called Valve-enabled Lysis, paper- based RNA Enrichment, and RNA Amplification Devices (VLEAD). VLEAD will integrate sample preparationâ€Â"" including virus lysis and RNA enrichmentâ€Â""with nucleic acid amplification for simultaneous detection of these viruses. To achieve the goal, we aim to (1) develop multiplexed VLEAD for simultaneous detection of ZIKV, DENV, CHIKV and MAYV; (2) optimize VLEAD using various samples and compare the suitability of the device for urine, saliva and blood samples; and (3) validate VLEAD using clinical samples and compare VLEAD with the benchmark methods including conventional RT-PCR. The significance of the research lies in the following aspects. First, these mosquito-borne RNA viruses are a public health concern. An accurate and sample-to-answer virus detection platform at POC will be useful for clinical care and patient management. Second, a large percentage of these virus infections are asymptomatic, thus a non-invasive POC platform would be very beneficial for screening the general population in the infected area and monitoring virus transmission. Third, the VLEAD platform can be adapted for detecting other pathogens of interest, with a potential to have more societal impacts.",,2025,UNIVERSITY OF FLORIDA,371905,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P22078,1R56AI172252-01A1,Infant Immunologic and Neurologic Development following Maternal Infection in Pregnancy during Recent Epidemics,"Abstract/Summary The massive outbreak of newly emerged coronavirus disease 2019 (COVID-19) saw rapid global spread, leading to a pandemic infection and an unprecedented global health emergency. Just years before, we witnessed the devastating impact of Zika virus (ZIKV) to unborn fetuses in the Americas. This proposal responds to the need to fill critical gaps in the understanding of the clinical repercussions of antenatal infections such as ZIKV and SARS-CoV-2 infection in pregnant women to the developing immune system of their infants, through the evaluation of cellular and humoral immune responses and clinical and neurodevelopmental outcomes following maternal immune activation (MIA) in this vulnerable population. Our team of researchers has been collaborating over the last 7 years to characterize the clinical and cellular effects of in utero transmission of Zika virus (ZIKV), with the collection of specimens from over hundreds of mother- infant pairs from Brazil. We reported on multiple obstetrical and clinical outcomes of infants with congenital ZIKV infection in the literature, including that ZIKV vertical transmission rate is at least 65%, that infected children do not develop ZIKV specific neutralizing antibodies despite an early IgM response, and that maternal humoral immune responses tend to be robust with highly neutralizing activity. During the COVID-19 pandemic we established a cohort of mother-infant pairs at UCLA and Fiocruz, Rio de Janeiro and controls with mother-infant dyads enrolled to date in both places. We are utilizing the existing infrastructure and scientific methods developed in the aftermath of the ZIKV epidemic to further evaluate clinical, cellular humoral and inflammatory parameters predicting immunologic outcomes in infants and children exposed to either maternal ZIKV and SARS Cov2 infection. The main goal of the proposed research is to comprehensively characterize repercussions of MIA on infant immune development and clinical outcomes, with a focus on immune pathogenesis. We include a longitudinal cohort of 200 mother- infant pairs with COVID-19 and 100 healthy control mother-infant pairs in the US and Brazil and 200 mother-infant pairs with ZIKV in Brazil and 100 healthy control pairs at the same clinical sites to address these goals. This RO1 proposes to evaluate the repercussions of MIA on infant well- being and immune development. State of the art technology is used to address the scientific aims, with the research led by experts in the field of immunology, infectious diseases & congenital infections who have ongoing successful, productive partnerships. The data rendered will be crucial for the knowledge of immune pathogenesis in pediatric populations with antenatal viral exposures.",,2024,UNIVERSITY OF CALIFORNIA LOS ANGELES,369974,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2023 +P22080,1R01AI175303-01,Zika virus nonstructural protein 5 inhibition of interferon signaling,"PROJECT SUMMARY All vector-borne flavivirus NS5 proteins suppress host type I interferon (IFN) signaling, which is critical to successfully infecting humans and causing disease. Inhibitors of this function of NS5 or viruses engineered to lack this activity may be effective antiviral therapies and attenuated vaccines, respectively. However, a deeper understanding of how the flavivirus NS5 protein acts to suppress IFN is needed. Despite the importance of inhibiting IFN signaling, and the high degree of sequence conservation between NS5 proteins within this genus, flaviviruses have evolved numerous distinct ways to antagonize this innate immune response. Many flavivirus NS5 proteins, including those of dengue (DENV), Zika (ZIKV), and yellow fever (YFV) viruses, inhibit the Signal Transducer And Activator Of Transcription 2 (STAT2) protein, which is a transcription factor that mediates IFN signaling. In this application, we propose to fill critical gaps in our understanding of the ZIKV NS5-STAT2 interface by defining the essential viral and host genetic determinants for this interaction at the highest possible, single amino acid, resolution through deep mutational scanning (DMS). In Aim 1, we will screen libraries of all possible single amino acid ZIKV NS5 variants for the ability to suppress IFN signaling. We will examine these determinants in a range of flaviviruses to understand functional conservation and mechanisms. In Aim 2, we will identify how STAT2 genetics impact the ability of ZIKV NS5 to suppress IFN signaling and mediate infection. Finally, in Aim 3 we will define how ZIKV NS5 induces the degradation of human STAT2 by identifying the STAT2 sites where NS5 induces ubiquitination and the host factors ZIKV NS5 recruits to mediate this modification. The results of this project will provide in-depth insights into flavivirus host cell interactions and replication mechanisms that may aid in the development of therapies for ZIKV, and could perhaps be further applied in combating other future virus outbreaks.",,2027,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,854154,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2023 +P22081,5U24AI152170-04,"Multiplex serological assays to support arbovirus diagnosis, surveillance and vaccines","Abstract At a global level, ongoing ecological, environmental and demographic changes favor the survival and expansion of several mosquito and tick species that transmit arboviruses. Aedes mosquito species that thrive in urban environments created by humans are responsible for epidemics of several flaviviruses [dengue virus (DENV) serotypes 1, 2, 3, 4; Zika virus (ZIKV); yellow fever virus (YFV)] and alphaviruses [chikungunya virus (CHIKV) and Mayaro virus (MAYV)]. Laboratory-based diagnosis and surveillance for arboviruses is difficult because most infected individuals are asymptomatic or develop a mild undifferentiated febrile illness. Serological assays have been developed for the detection of recent or past arboviral infections, but the utility of these assays is severely limited by antibody cross reactivity between related viruses. For example, when ZIKV emerged in many regions of the Americas where greater than 80% of the population was dengue-immune, with current serological assays, it was difficult, if not impossible, to identify infected individuals or monitor the spread of ZIKV at a population level, and likewise to now detect new DENV infections in areas that experienced intense ZIKV epidemics. Our studies over the past 10 years demonstrate that people exposed to flavivirus infections reliably develop antibodies to epitopes that are unique to each flavivirus as well as cross-reactive antibodies. Using our discoveries about the location of immunodominant virus type-specific epitopes, we have produced novel recombinant antigens and demonstrated their utility for the type-specific diagnosis of arboviruses. Under Specific Aim 1 of this proposal, we will build on these discoveries to develop a sample-sparing, microsphere bead-based multiplex assay for the type-specific and sensitive detection of recent or past arbovirus infections. Our initial studies will focus on 8 arboviruses transmitted by Aedes aegypti and Aedes albopictus mosquitos because these viruses share a similar ecology and co-circulate in the same human populations. At a second stage, we will expand the coverage of the assay to detect infections with other arboviruses transmitted by other mosquito species and ticks. Several tetravalent DENV and ZIKV vaccines are currently being evaluated in human clinical trials. While vaccine developers have relied on neutralizing antibodies as a correlate of protection, recent results from clinical trials demonstrate that neutralizing antibodies alone are a poor correlate of vaccine safety and efficacy. We have identified flavivirus type- and epitope-specific antibody responses that are better predictors than neutralizing antibodies of vaccine safety and efficacy. Under Specific aim 2 of this proposal, we will develop a sample-sparing microsphere-based assay for the detection of epitope-specific vaccine-induced antibody responses that are correlated with protective immunity to each of the DENV serotypes and ZIKV. The technological advances and products from this proposal will enhance our ability to efficiently monitor arbovirus infections at the individual and population levels and also support the development of arbovirus vaccines.",,2025,UNIV OF NORTH CAROLINA CHAPEL HILL,413628,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +P22082,5R01AI149502-04,Multiplex Serodiagnostic Assays for Pathogenic Arboviruses in Brazil,"Abstract A critical need exists for highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses in geographic regions, such as Brazil, where multiple flaviviruses including Zika virus (ZIKV), four serotypes of dengue virus (DENV1-4), West Nile virus (WNV), and yellow fever (YFV), as well as chikungunya virus (CHIKV), Mayaro virus (MAYV) (both alphaviruses) and Oropouche virus (OROV) (a bunyavirus), are endemic. However, cross-reactivity of antibodies against different flaviviruses present major challenges, such that even neutralization tests cannot confirm a specific flavivirus infection among individuals who have experienced previous flavivirus infections. The objective of the proposed research is to develop highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses. The central hypothesis is that a combination of fusion loop (FL)-mutated VLPs and nonstructural protein 1 (NS1) proteins of different flaviviruses and recombinant proteins and VLPs of CHIKV, MAYV and OROV in multiplex formats can distinguish different arbovirus infections. The first Aim is to develop and validate multiplex IgG and IgM microsphere immunoassays (MIAs) based on recombinant proteins to distinguish arbovirus infections. We will employ recombinant NS1 proteins of 7 flaviviruses, envelope (E) 2 protein and nucleocapsid (N) protein of CHIKV, MAYV and OROV for multiplex IgG and IgM MIAs using Luminex 200 and test with 15 panels of convalescent-phase serum/plasma from individuals with confirmed arbovirus infections. The second Aim is to develop and validate multiplex IgG and IgM MIAs based on VLPs to distinguish arbovirus infections. We will use purified and FL-mutated VLPs of 7 flaviviruses and VLPs of CHIKV, MAYV and OROV, and test with 15 panels of serum/plasma as in Aim 1. The third Aim is to compare the multiplex IgM MIAs and IgG MIAs with currently available serodiagnostic assays to determine arbovirus seroprevalence in Bahia, a northeastern state with multiple arbovirus transmissions in Brazil. For serodiagnosis, we will test serum samples from patients with acute febrile illness and their follow-up at outpatient clinics of 4 study sites (Salvador, Feira de Santana, Itabuna and Campo Formoso) in Bahia. For seroprevalence study, we will enroll and test household members at communities of the 4 study sites. The proposed study is innovative as it employs two promising antigens (NS1 protein and FL-mutated VLPs) to overcome flavivirus cross-reactivity for seven flaviviruses, as opposed to traditional E protein-based tests, plus CHIKV, MAYV and OROV in two multiplex formats to discriminate arbovirus infections in Brazil. It would contribute to a detailed understanding of the epidemiology of 10 arbovirus infections in Bahia. The successful employment of the multiplex platforms can serve as a new paradigm for serodiagnosis and serosurveillance in countries where multiple arboviruses co-circulate. Most importantly, this research will facilitate the implementation of arbovirus vaccines, in particular ZIKV, DENV and CHIKV vaccines in endemic regions.",,2024,UNIVERSITY OF HAWAII AT MANOA,156500,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +P22083,5P20GM135004-04,Leveraging Zika virus driven myeloid cell responses to treat GBM,"Oncolytic viral therapy shows promise for high-grade solid tumors, but none have been shown to provide curative potential. This study explores the potential of harnessing the natural tropism of Zika virus (ZIKV) to target glioblastoma stem cells (GSCs) and reprogram the typically immune suppressive GBM tumor environment to an inflammatory, antigen-presenting environment that induces GBM-specific CD8+ T cell responses. The first goal of this proposal is to identify the cellular mechanisms that drive anti-tumor T cell responses following ZIKV treatment. Our research will examine the functional roles of two distinct myeloid cell subsets induced following ZIKV treatment - CCR2+ monocytes in the tumor microenvironment (TME) and dendritic cell subset-2 (DC-2s) in draining lymph nodes (dLN) - in driving anti-tumor T cell responses against GBM. Additionally, our study will examine the synergistic therapeutic potential of a highly novel Flt3 ligand therapy and ZIKV combination therapy as a strategy to activate both dendritic cell subset-1 (DC-1s) and DC-2, to maximize anti-tumor CD8+ T cell responses and subsequent GBM rejection. This research is significant because 1) it addresses the potential of ZIKV as an effective oncolytic virus for GBM treatment, 2) identifies key cellular mechanisms that contribute to its anti-tumor effects and 3) addresses the current failure of immunotherapy and maps a therapeutic path forward.",,2025,UNIVERSITY OF LOUISVILLE,148174,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2023 +P22084,5R01AI155983-03,Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and -experienced Individuals,"Project Title: Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and - experienced Individuals Project Summary Zika virus (ZIKV) is a member of the flavivirus genus that recently precipitated widespread cases of neurological pathology and congenital neurologic defects. In response, a multilateral coalition of investigators designed and developed multiple vaccine candidates that elicited potent ZIKV-neutralizing antibodies, which were shown to correlate with disease protection in animal models. Despite these advances, it remains unclear how the ZIKV immunization antibody response is shaped in humans with and without prior exposure to other flaviviruses, such as dengue virus (DENV), Japanese encephalitis (JEV) or yellow fever virus (YFV); particularly as these viruses all have significant epidemiologic overlap with ZIKV. Our long-term goal is to understand the underlying humoral mechanisms generated by flavivirus vaccination, which can provide long-term protection in flavivirus-naïve and/or -experienced populations. Such information would guide vaccination strategies in flavivirus-endemic areas or among flavivirus-naïve individuals traveling to endemic areas. The overall objective of this proposed research is to evaluate the specificity and function of the B cell repertoire elicited by ZIKV vaccination in flavivirus- naïve and -experienced individuals. To achieve these goals, this research will utilize leading-edge technologies to sequence B cell receptors (BCRs) from flavivirus-specific, single B cells using RNAseq and Next Generation Sequencing (NGS). BCRs will be compared between Zika vaccinated individuals, and to previously published monoclonal antibodies, to determine the prevalence of B cell lineages, gene assignment, degree of somatic hypermutation (SHM), and lengths of heavy chain complementary-determining region 3 (HCDR3). Common B cell lineages will be expressed as monoclonal antibodies and evaluated for their specificity, function, structural, and ability to protect against flavivirus challenges in mouse models. A total of 40 samples will be evaluated from individuals representing 5 groups in 3 different Phase I Zika vaccine clinical trials: a) Flavivirus-naïve individuals who were vaccinated using a Zika purified inactivated whole virus vaccine (ZPIV) b) Flavivirus-naïve individuals who were vaccinated with an adeno-vectored Zika M-E (Ad26.ZIKV.M-Env) c) Individuals living in Puerto Rico with prior dengue infection who were ZPIV vaccinated d) JEV (IXIAROÃ'®) vaccinated individuals who were ZPIV vaccinated and e) YFV (YV-VAXÃ'®) vaccinated individuals who were ZPIV vaccinated. Flavivirus-naïve, Zika vaccinated individuals (Groups a-b) will be explored in Aim 1 and Flavivirus-experienced individuals, either by prior infection (Group c) or by prior vaccination (Groups d-e), will be explored in Aim 2. Aim 3 will examine a late timepoint (6 months) following the last ZPIV vaccination to determine the longevity of the circulating B cell lineages characterized in Aims 1 and 2. Evaluating prevalent B cell lineages responding to Zika vaccination will reveal the specificity, function and durability of the humoral response among individuals living in different regions. These studies will provide insights into the potency and durability of ZIKV vaccine responses in both flavivirus- naïve and -experienced individuals and may translate into vaccine strategies that yield long-lived protection.",,2027,HENRY M. JACKSON FDN FOR THE ADV MIL/MED,300000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Characterisation of vaccine-induced immunity",2021 +P22085,1F31AI176618-01,NK killing of coronavirus-infected cells,"Abstract Natural killer (NK) cells are innate lymphocytes that kill tumor and virus-infected cells, independently of peptide antigens. NK cells recognize target cells through activating and inhibitory NK receptors, which interact with specific ligands on the target cell surface. The balance of activating and inhibitory receptor signaling determines whether target cells are killed. Our lab recently found that the most conserved and universally expressed NK activating receptor, NKp46, recognizes cells undergoing endoplasmic reticulum (ER) stress by binding to externalized calreticulin (ecto-CRT), an ER chaperone that translocates to the cell surface under conditions of ER stress. Ecto-CRT binds to and activates NKp46, leading to killing of tumor, senescent, and Zika virus (ZIKV)- infected cells. We also found that ER stress during ZIKV infection downregulates the major histocompatibility complex (MHC) ligands of NK inhibitory receptors. Coronavirus (CoV) replication is tightly linked to the ER. CoV mature by budding into the ER-Golgi intermediate compartment (ERGIC), where the nucleocapsid-genomic RNA complex is enclosed within a membrane containing the membrane-bound structural viral proteins, S, E, and M. These proteins are expressed on the ER. Massive production of viral proteins along with depletion of the ERGIC membrane by budding and egress of progeny virions disrupts the ER during CoV infection, as shown using murine hepatitis virus as a model system. Given our previous work showing recognition of ZIKV-infected and ER stressed cells via NKp46/ecto-calreticulin, we wondered whether CoV-infected cells may also be recognized by NK via the same interaction. Most papers studying NK responses to SARS-CoV-2 have focused on antibody- dependent cellular cytotoxicity (ADCC) and are thus measuring a function of NK cells that depends on an adaptive immune response. Three papers investigated antibody-independent NK cell interactions with SARS- CoV-2-infected target cells in vitro, and suggest that NK cell co-culture with infected targets suppresses viral replication by measuring a reduction in viral protein or RNA. However, none of these publications explored how NK recognize infected cells. In preliminary experiments I assayed for ER stress and CRT externalization during infection by the avirulent human CoV OC43. My preliminary data confirm that OC43 infection induces upregulation of ER stress genes and show that CRT externalization occurs during infection. Based on these data, I hypothesize that CoV replication causes ER stress, externalization of CRT, and downregulation of NK inhibitory receptor ligands, causing CoV-infected cells to be recognized by NKp46 and killed by NK. I will investigate this central hypothesis by measuring expression of activating ecto-CRT and inhibitory MHC ligands on the surface of CoV-infected cells (Aim 1). I will then test the ability of primary and NK cell lines to kill CoV- infected cells and determine whether the killing of infected cells, if present, is mediated by the NKp46/ecto-CRT interaction (Aim 2). I will investigate this system using both avirulent OC43 and virulent SARS-CoV-2. The proposal will further our understanding of how the innate immune system may defend against CoV infection.",,2026,HARVARD MEDICAL SCHOOL,41677,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P22086,5R01AI153434-03,Flavivirus immunity in endemic and non-endemic human cohorts,"PROJECT SUMMARY The global spread of the arthropod borne flaviviruses dengue (DENV1-4) and Zika (ZIKV) viruses are major global public health challenges. World health organizations are calling for scientific communities to respond to this emerging threat with vaccines, therapeutics and diagnostics. However, existing gaps in fundamental knowledge about DENV and ZIKV immunity, specifically how type-specific immunity to each serotype develops and is sustained, makes rational vaccine development particularly difficult. The dominant immunity model comes from human challenge studies on DENV (1910’s-1940’s) and posits that first infection induces neutralizing antibodies that provide life-long sterilizing immunity to repeat infections by the same (homotypic) serotype virus, and this model has been extended to ZIKV without rigorous evaluation. However, recent studies from DENV endemic regions provide evidence of homotypic re-infection and natural immune boosting over time and our preliminary data from a non-endemic, Portland, Oregon resident DENV and ZIKV immune cohort show type- specific Abs decay â€Â"" lose both potency and breadth - over time, calling into question sterilizing immunity and leading us to hypothesize that natural flavivirus (ZIKV and DENV) protective immunity is context dependent: in endemic transmission settings intermittent asymptomatic boosting maintains potency and breadth of virus specific immunity and in non-endemic or very low transmission settings potency and breadth of flavivirus immunity significantly wanes. To test this hypothesis, we propose to prospectively characterize and compare DENV and ZIKV immunity in a regularly re-exposed endemic cohort in Ponce, Puerto Rico with immunity in an un-boosted, non-endemic cohort of DENV immunes in Portland. This is a controversial and novel hypothesis that will call for substantial supporting evidence, hence we will compare and contrast three highly relevant and related markers of boosting between the two cohorts: The potency and breadth of neutralizing serum DENV and ZIKV specific Abs (Aim 1), the frequency of and potency of DENV and ZIKV non-structural protein 1 (NS1) specific antibodies (Aim 2), and the frequency and specificity of DENV and ZIKV specific memory B-cells (MBCs) (Aim 3). We expect to find that Abs and MBCs decline at a significantly greater rate in individuals from the non- endemic setting compared to the endemic setting supporting the hypothesis that boosting plays a critical role in natural immunity for these viruses, with implications for future vaccine development. Because MBCs are functionally linked to Abs, quantifying virus specific MBCs tests a mechanistic connection between repeat infection and Ab titer boosting. Our proposed work will comprehensively assess the role transmission context plays in flavivirus immunity using two highly relevant and mechanistically linked determinants (Ab and MBC). Irrespective of specific results, the knowledge obtained from the proposed work will be essential to DENV vaccine development and mechanistic understanding of flavivirus Ab mediated immunity.",,2026,OREGON HEALTH & SCIENCE UNIVERSITY,385867,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P22087,5R01AI153419-03,Mechanistic Insights into flavivirus NS5-mediated STAT2 Suppression,"The family of flavivirus consists of over 90 vector-borne, single-stranded RNA-containing viruses, including Dengue virus (DENV) and Zika virus (ZIKV), which cause major epidemics among humans and pose a serious threat to global public health. No vaccines or antivirals exist to prevent or treat infections caused by DENV, ZIKV, and some other flaviviruses. To establish infection, flaviviruses need to overcome the antiviral state induced by type 1 interferon (IFN-1), the first line of host defense. In this regard, flaviviruses have encoded several antagonists to suppress IFN responses. For example, the nonstructural NS5 proteins of DENV, ZIKV, and some other flaviviruses have been shown to be potent suppressor of IFN signaling, targeting different steps of the IFN signaling pathway. Like DENV, ZIKV NS5 protein bind human signal transducer and activator of transcription 2 (hSTAT2) protein and trigger its proteasomal degradation, albeit using different downstream mechanisms. To elucidate the mechanistic basis of flavivirus NS5-mediated hSTAT2 suppression, we propose to provide structural insight into the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 complexes, which, in turn, will guide interrogation of the consequence(s) of the flavivirus NS5-hSTAT2 interactions in proteasome-mediated degradation of hSTAT2 and suppression of IFN signaling. Toward this goal, we will use structural, biochemical, molecular, cellular and virology approaches to investigate the structural basis of the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 interactions and their functional consequence. In Aim 1, we will establish the structural basis of the ZIKV-hSTAT2 interaction by using X-ray crystallography and cryo-electron microscopy and validate our observations with mutational and in vitro pull-down analyses. In Aim 2, we will examine the ZIKV NS5-hSTAT2 interaction at a cellular level and investigate the functional consequence of the ZIKV NS5-hSTAT2 interaction through evaluation of the mutational effects of ZIKV NS5 on hSTAT2 degradation, IFN response and viral infection. The results of these studies will provide critical structural and functional insights into the virus- and species-specific ZIKV NS5-hSTAT2 interaction, thereby establishing a mechanistic link between flavivirus NS5 proteins, hSTAT2 degradation, suppression of the IFN response and viral infection. Results from the proposed studies will ultimately benefit development of novel antivirals and live vaccines against flaviviruses infection.",,2026,UNIVERSITY OF CALIFORNIA RIVERSIDE,388750,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22088,5R01AI145918-04,Trade-offs between Arbovirus Transmission and Clearance in Native and Novel Hosts,"Research Summary The recent introduction of Zika virus (ZIKV) into the New World sparked concern that the virus would emerge into a sylvatic cycle in American non-human primates (NHPs) and mosquitoes. The ability of a pathogen to emerge into a novel host species is determined, in part, by the virulence of that pathogen in the novel species. Current theory on the evolution of virulence rests on the premise that pathogen fitness is maximized by optimizing the trade-off between instantaneous pathogen transmissibility and duration of infection. While most theoretical studies of virulence evolution have focused on the trade-off between transmission and host mortality, the majority of pathogens do not kill their hosts. Instead, most infections are curtailed by the host immune response, leading to a transmission-clearance trade-off. Studies of the transmission-clearance trade-off are scarce, but we have previously found that, across multiple studies in the literature, there is an inverse relationship between peak virus titer and duration of infection when arthropod-borne viruses are experimentally inoculated into natural hosts. Moreover, we have leveraged these data to model alternate transmission strategies, namely a “tortoise” strategy of low magnitude, long duration viremia and a “hare” strategy of short duration, high magnitude viremia and found that arboviruses that adopted a tortoise strategy had higher rates of persistence in both host and vector populations. Nonetheless current understanding of transmission-clearance trade-offs in arboviruses is rudimentary, and integrated experimental and modeling studies of arbovirus trade-offs in ecologically-relevant host and vector species are needed to appropriately assess the risk of establishment of sylvatic cycles in new areas and the subsequent risk of emergence from such cycles. To this end, we will quantify dynamics of ZIKV and dengue virus (DENV) infection, immune response, and transmission in native NHP hosts (cynomolgus macaques) as well as novel, American NHPs (squirrel monkeys) to identify transmission-clearance trade-offs, and we will build models to predict the impact of such trade-offs on virus persistence in host populations. DENV is chosen as a counterpoint to ZIKV because, despite circulating in humans in the Americas for centuries, it has not yet established an American sylvatic cycle [17]. We will test four specific hypotheses: (i) In native hosts and novel hosts, sylvatic arboviruses experience a transmission-clearance trade-off; (ii) In native and novel hosts, the innate immune response shapes the transmission-clearance trade-off; (iii) Sylvatic arboviruses experience different transmission-clearance trade-offs in native hosts and novel hosts, resulting in less transmission from novel hosts; (iv) DENV and ZIKV lineages from human-endemic transmission cycles experience different transmission-clearance trade-offs than their sylvatic ancestors in native NHP hosts, but similar patterns in novel NHP hosts.",,2025,NEW MEXICO STATE UNIVERSITY LAS CRUCES,549168,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2020 +P22089,5R01AI158194-03,Structure-based design of broad flavivirus immunogens,"SUMMARY Dengue virus is a mosquito-transmitted flavivirus that causes an estimated 390 million human infections each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions. Primary infection by a single DENV serotype results in febrile illness and subsequent durable immunity to that serotype. Secondary infections by heterotypic serotypes can lead to severe shock syndrome and death. Severe Dengue disease is caused in part by cross-reactive antibodies elicited during primary infection that can bind heterologous DENV serotypes but cannot neutralize them. Instead, these non-neutralizing antibodies facilitate entry and infection in Fcγ receptor-positive cells, thus causing ""antibody-dependent enhancement"" (ADE) of infection. While a live-attenuated four-component chimeric vaccine was recently deployed in 19 countries and Europe, this vaccine does not protect naïve individuals against symptomatic or severe infection, and may even exacerbate disease in some cases. Furthermore, the global emergence of Zika virus (ZIKV), and the potential for ADE between DENV and ZIKV, raises concerns for vaccine strategies containing most or all epitopes in the E glycoprotein. Nonetheless, the isolation and characterization of protective and, in some cases, broadly-neutralizing antibodies indicates that certain epitopes within the E glycoprotein may have the capacity to elicit broadly protective responses. Here, we utilize innovative protein engineering approaches to develop “immune-focused” antigens as potential vaccine candidates, in which epitopes that induce non-neutralizing antibodies are masked by engineered mutations or glycosylation. Our hypothesis is that masking of these unfavorable epitopes will skew the immune response toward a stronger neutralizing, protective, and broad response. Aims 1 and 2 focus on critical epitopes in DENV and ZIKV E domain III (EDIII), and Aim 3 explores glycan masking of the ZIKV E prefusion dimer to immune focus on the E-dimer epitope (EDE). EDIII is attractive for subunit vaccine design because it is the target of potently neutralizing and protective antibodies for both DENV and ZIKV. However, immunization with wild-type EDIII protein results in induction of both neutralizing and non-neutralizing antibodies that engage a variety of epitopes. We have used phage display to mask unproductive epitopes of DENV and ZIKV EDIIIs by mutation, while maintaining neutralizing epitopes. These “resurfaced EDIIIs” (rsDIIIs) will be conjugated to protein nanoparticles and their capacity to induce neutralizing and protective antibody response in mice evaluated. To immune focus the prefusion E dimer on the EDE, we have developed a mammalian display system that allows for rapid evaluation of E dimer constructs for binding to EDE mAbs. We will utilize this system to screen variants with multiple engineered glycosylation sites that mask the surface outside of the EDE. The most promising candidates will be tested for their capacity to induce EDE-like mAbs in mice. This work will provide a proof-of-concept for novel subunit vaccine candidates against DENV, ZIKV, and possibly other flaviviruses of global concern.",,2026,ALBERT EINSTEIN COLLEGE OF MEDICINE,738795,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22090,1R35GM150778-01,Understanding the antiviral roles of acellular RNA quality control pathway,"Abstract Eukaryotic cells use multi-layered strategies to ensure the fidelity of gene expression. One of the best-studied RNA quality control pathways is Nonsense-mediated mRNA decay (NMD), a ribosome-associated surveillance machinery that recognizes and degrades cellular transcripts with premature termination codons (PTC). Initially identified as a mechanism to rid the cell of faulty mRNAs, it is now known that NMD also regulates the expression of 5-10% of cellular transcripts with important functions in cell differentiation, homeostasis, cellular stress responses, and more. In addition, recent studies have shown that many proteins of the NMD pathway function in the cell-autonomous defense against RNA viruses, including human-pathogenic alphaviruses, coronaviruses and flaviviruses. As obligate intracellular parasites, these viruses interface closely with cellular mRNA processing pathways, and we can gain new insight to NMD functions by understanding how the machinery is repurposed to fight viral infection. We currently have a very incomplete picture of NMD functions during viral infection. Many viruses lack PTCs or other NMD-inducing features, and it is not known whether NMD proteins recognize viral RNA in manners similar to canonical NMD, or through new and unusual interactions or mechanisms. Moreover, NMD is often globally downregulated during virus infection, suggesting that viruses have mechanisms to rewire the antiviral NMD network. Using the flavivirus Zika virus (ZIKV) as a model RNA virus, we aim to understand the molecular interactions between the NMD machinery and viral infection. We will dissect the NMD-ZIKV protein-protein and protein-RNA interaction network with a multi-disciplinary approach that combines virology with RNA biochemistry and high-throughput assays to link molecular interactions to cellular phenotypes. Specific questions addressed within this study are: 1) How do NMD proteins interact to fight viral infection? 2) Are there specific features in the viral RNA that trigger NMD, and if so, how are they recognized by the NMD machinery? 3) How do viral proteins inhibit NMD? And 4) Are antiviral NMD functions conserved in the important mosquito host of flaviviruses? Collectively, our study will provide new insight into an important cell-autonomous antiviral defense network. In addition, by studying the unusual ways in which NMD is regulated during virus infection, we hope to discover new cellular functions of the NMD machinery itself.",,2028,COLUMBIA UNIVERSITY HEALTH SCIENCES,411250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P22091,5U01AI148069-04,Quanitifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases,"Project Summary/Abstract Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes- borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections. Novel vector control approaches and intervention delivery strategies to contain ABVs are urgently needed. Targeted indoor residual spraying (TIRS, applying residual insecticides on Aedes aegypti resting sites such as exposed low walls [<1.5m], under furniture, and on dark surfaces) is a rational vector control approach that exploits Ae. aegypti resting behavior to focalize insecticide applications with no loss in residual efficacy. Recently published systematic reviews have identified TIRS as a very promising approach for ABD prevention, but highlighted the limited evidence-base for this intervention due to the absence of efficacy estimates from randomized controlled trials with epidemiological endpoints performed in endemic settings. In response to such critical need, we will pursue a two-arm, parallel, unblinded cluster randomized trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory- confirmed (virologically or serologically) ABV clinical disease (e.g., dengue, Zika or chikungunya) (primary endpoint). Secondary endpoints will include: a) Laboratory-confirmed (serologically) DENV, CHIKV or ZIKV seroconversion in children aged 2-15 at enrollment; b) Ae. aegypti mosquito infection rates with DENV, CHIKV or ZIKV; c) Ae. aegypti indoor entomological indices. The trial will be conducted in the city of Merida (Yucatan State, Mexico, population ~1million), where we will prospectively follow a population of 4,600 children 2-15 years at enrollment, distributed in 50 clusters of 5x5 city blocks each (~92 children per cluster), randomly allocated to receive either TIRS treatment (n=25) or not (n=25). Trained personnel from the Federal Ministry of Health will perform TIRS in all houses from the treatment clusters ~1-2 months prior to the beginning of the peak ABV transmission season. Active monitoring for symptomatic ABD infections will be performed by field nurses and doctors through weekly household visits and enhanced surveillance (phone calls, monitoring of suspected cases to Merida’s hospital/clinic system), whereas annual sero-surveys will be performed after each transmission season. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to guide insecticide applications; change to preemptive control (pre- ABV transmission season rather than in response to symptomatic cases); the use of insecticide formulations to which Ae. Aegypti is susceptible.",,2025,EMORY UNIVERSITY,1282318,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,"Vector control strategies | Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures",2020 +P22092,3K22AI144050-02S1,Characterization of a human-specific positive regulator of flavivirus infection,"Project Summary/Abstract Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV) or Dengue virus (DENV) are cause of great health and economic concerns worldwide. YFV is the prototypical member of the flavivirus genus, and one of the first human pathogenic viruses that has been identified. Despite the development of a very potent vaccine in the 1930’s, YFV still represents a real theat. Recent outbreaks in Angola and Brazil, over the past two years, occurred in areas with low vaccination coverage. These resurgence events have exemplified the threat and have highlighted the need for the protection of an estimated 400 to 500 million people worldwide. Facing a significant vaccine shortage, fractional doses of vaccine are now used during vaccination campaigns despite no/limited evidence of long-term protection, hence underscoring the urgent necessity of developing novel strategies to clinically manage future YFV outbreaks. Our knowledge of the YFV infectious cycle in vitro and in vivo is extremely limited which has ultimately hampered the development of specific therapies to treat YFV infection, as none is currently available. I recently identified a novel host regulator of YFV infection in human cells that is required for effective YFV infection and replication in vitro. As it is not expressed in mice, this factor could also contribute to the human/primate-specific tropism of YFV. Building on a robust set of preliminary data, I hypothesize that this factor regulates RNA replication or protein translation through direct binding to viral elements. In Aim 1, I will explore the mechanisms by which this factor regulates the replication of the YFV vaccine strain YFV-17D in vitro as well as the host and virus determinants that govern such regulation. In Aim 2, I will determine the role of this factor on the replication of a virulent YFV strain, YFV-Asibi, as well as of other flaviviruses of interest such as ZIKV and DENV. I will also seek to explore the role of this factor using more relevant cell culture system such as primary human hepatocytes by using specific inhibitor of this factor. In Aim 3, I will use a humanized mouse model I recently developed and that is permissive to YFV infection to evaluate the role of this factor on YFV-Asibi and YFV-17D replication in vivo, by treating mice with specific inhibitor of the identified host factor. Altogether, my strong expertise in studying YFV virus in vitro and in vivo, combined with the different viral tracking tools and in vivo models I have previously developed, position me very well to conduct the proposed research. This research could provide novel avenues for the specific treatment of YFV infection and enhance our understanding of the host-pathogen interactions that define flavivirus pathogenicity. This K22 Career Transition Award will help me achieve my scientific and career goals, which consist of transitioning toward an independent assistant professor position and establishing an independent NIH-funded research program aiming at elucidating the mechanisms of flavivirus pathogenicity.",,2024,BOSTON UNIVERSITY MEDICAL CAMPUS,75600,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22093,5R01AI168003-02,Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leak,"Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leak ABSTRACT The flavivirus (FV) genus contains medically important mosquito-borne human pathogens that cause a major global disease burden. While dengue (DENV), yellow fever (YFV), and Zika (ZIKV) viruses are systemic, and West Nile (WNV), Japanese encephalitis (JEV), and Zika viruses cause neurotropic infections, each FV can cause severe disease characterized in part by endothelial barrier dysfunction â€Â"" the most classic example being vascular leak in severe dengue. This may result from overproduction of vasoactive cytokines as well as viral factors. The highly conserved FV non-structural protein 1 (NS1) is secreted from infected cells and circulates in the blood of infected humans. We and others have shown that FV NS1 can trigger endothelial barrier disruption in vitro and vascular leak in mice, independently from virus infection. In our current R01, we showed that endo- cytosis of FV NS1 into endothelial cells (ECs) followed by activation of key enzymes such as cathepsin L and heparanase leads to disruption of the endothelial glycocalyx layer (EGL) as well as mislocalization of intercellular junction proteins, both critical for maintaining endothelial barrier integrity. Interestingly, we found that FV NS1 proteins display exquisite tissue tropism, triggering EC dysfunction in vitro and in vivo in a manner reflecting tissue tropism and disease manifestations of each virus. While FV NS1 tissue tropism was determined by differential EC binding and internalization, downstream activation of key enzymes and signaling pathways required for pathogenesis appear to be conserved across FVs. However, host factors, viral determinants, and mechanisms mediating these processes are unknown. We hypothesize that distinct host factors on tissue- specific ECs mediate FV NS1 cell binding and internalization, leading to endothelial barrier dysfunction, virus dissemination, and different FV disease manifestations. In contrast, once a FV NS1 protein is internalized, we hypothesize that downstream steps of EC dysfunction are comparable â€Â"" thus pointing the way to a pan-FV intervention. Here, we expand our previous work by identifying and characterizing host glycans, proteins, and NS1 determinants required for tissue-specific cell binding and internalization of NS1 in human ECs, mouse models, and clinical samples. We also define common mechanisms by which FV NS1 proteins trigger pathology. In Aim 1, we will identify and characterize host glycans and FV NS1 determinants required for differ- ential binding to tissue-specific ECs. In Aim 2, we will identify proteinaceous NS1 receptors required to initiate EC dysfunction and define mechanisms by which FV NS1 proteins mediate disruption of the EGL and intercellular junctions in tissue-specific ECs in vitro and in vivo. Aim 3 investigates the impact of FV NS1-mediated endothelial dysfunction on FV dissemination and pathogenesis in mouse models and human clinical samples from severe dengue and YF patients in Vietnam, Nicaragua and Brazil. This work is supported by experts in glycobiology, FV structural biology and biochemistry, vascular biology, FV pathogenesis and animal models, and clinical investigation and should identify biomarkers of severe FV disease and novel viral and host therapeutic targets.",,2027,UNIVERSITY OF CALIFORNIA BERKELEY,670954,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2022 +P22094,1R21NS130282-01A1,RIPK3-dependent suppression of excitotoxicity during neuronal flavivirus infection,"Abstract While neurons were previously believed to be immunologically inert, recent advances have redefined our understanding of the intrinsic immunological activity of this cell type. Notably, neurons exhibit robust innate immune responses to viral infection, often employing adaptations of antiviral processes that reflect their unique cell biology. We and others recently described one such adaptation, in which activation of receptor interacting protein kinase-3 (RIPK3) in neurons during flavivirus infection does not result in necroptotic cell death, the canonical function of this protein. Instead, neuronal RIPK3 activation drives a cell death-independent transcriptional program that includes a broad variety of antiviral and immunoregulatory genes. However, while roles for RIPK3 in coordinating neuronal inflammatory responses are now established, the potential impact of RIPK3 activation on other features of neuronal cell biology, including neurotransmission, remain unexplored. In preliminary experiments, we have shown that RIPK3 activation following neuronal Zika virus infection supports expression of a broad class of genes involved in synapse regulation, including neurotransmitter receptor trafficking and internalization. We also show that increased neuronal cell death and animal mortality in neuron cultures and mice lacking RIPK3 can be rescued by pharmacologic blockade of the ionotropic glutamate receptor NMDAR. We thus hypothesize that RIPK3 protects neuronal viability during Zika virus infection via suppression of NMDAR-dependent excitotoxic cell death. We will test this idea using an innovative combination of pharmacogenetics, imaging, molecular biology, and electrophysiological approaches. If successful, these studies will define a new, pro-survival function for a canonical cell death protein in neurons, as well as bring new clarity to the impact of innate immune signaling on neurotransmission.",,2025,"RUTGERS, THE STATE UNIV OF N.J.",431750,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P22096,1F30AI174788-01A1,Strategies for next-generation flavivirus vaccine development,"Dengue virus (DENV; DV) is the most common mosquito-borne virus in the world, with 4 billion people living in regions that put them at risk for infection by any of its four serotypes (DV1-4). Infection by DV and its related flavivirus Zika virus (ZIKV; ZV) may clinically manifest as mild flu-like symptoms, rash, and arthralgia. Severe DV cases can progress into hemorrhagic fever and shock syndrome, while severe complications of ZV infection include Guillain-Barre syndrome in adults and neonatal microcephaly. Severe dengue is associated with antibody-dependent enhancement (ADE) of infection, a phenomenon seen as potentially fatal. In response to a primary DV infection, the immune system produces antibodies that can bind and neutralize that serotype to resolve infection. However, during a subsequent infection by a heterotypic DV serotype or ZV, some antibodies from the primary infection are re-elicited but may poorly neutralize the heterotypic infection; thus, instead of eliminating infection, these antibodies promote uptake of active virus into Fcγ receptor-expressing immune cells and increase viremia and levels of pro-inflammatory cytokines. Currently, there is a need for vaccines and anti- viral therapies for DV and ZV that do not carry the risk of inducing ADE. To avoid ADE, a significant goal for DV and ZV vaccine development is to elicit broadly protective antibodies, as opposed to broadly reactive, non- neutralizing ones. We determined two glycoproteins expressed by DV and ZV as favorable candidates for immunogen design. Neutralizing, protective antibodies against DV and ZV have shown to target domain III (DIII) of E glycoprotein, which is critical for viral entry and cell attachment. However, non-neutralizing, ADE-inducing antibodies were also identified to bind to other motifs on WT DIII. Targeting WT NS1 glycoprotein, which plays a key role in viral replication and endothelial dysfunction, may reduce disease severity without ADE, but it may elicit non-neutralizing, even autoreactive antibodies. To address these challenges, structure-based approaches may be used for immunogen mutagenesis and multivalent display of these immunogens. This proposal will investigate methods to increase the immunodominance of heterologous epitopes found on the lateral ridge (LR) of DIII and the β-ladder of NS1, while masking certain epitopes on these immunogens, to induce broad humoral protection and mitigate severity of disease. We previously demonstrated the strong immunoprotecting potential of a homotypic ZV immunization strategy, which involved the multivalent display of a LR-focused DIII mutant onto nanoparticles. We will study the effectiveness of various heterotypic nanoparticles as cross-immunization strategies against ZV and DV and characterize underlying humoral responses to the immunizations in mice (Aim 1). We will then explore the design of miniβ, a novel NS1 mutant which may be employed to curb disease progression without eliciting ADE or autoreactive antibodies (Aim 2). These studies will further our understanding of the adaptive immune response to flavivirus infections and may provide a framework for developing novel vaccines and antibody-based therapeutics.",,-99,ALBERT EINSTEIN COLLEGE OF MEDICINE,52694,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2024 +P22097,5R01AI156187-03,Probing Functional States and Inhibition of Flaviviral Proteases Using Nanopore Tweezers,"Project Summary Flavivirus are major mosquito-borne pathogens infecting millions of people worldwide each year. Currently there is no antiviral therapy available for treating West Nile, Dengue and Zika viral infections. The first vaccine CYD- TDV (Dengvaxia) against DENV was approved last year but shows only 56% overall efficacy against the four dengue serotypes. The flaviviral two-component NS2B/NS3 protease is required for viral replication and thus an attractive antiviral target. However, extensive screening and rational design efforts have failed to identify any clinically viable inhibitors at this point. Two key factors have likely contributed to the challenge. First, traditional screening efforts rely primarily on binding affinity to predict the drug efficacy. Yet, increasing evidence has emerged to show that the residence time of drug-target interaction is a more reliable predictor of in vivo pharmacological activity. These kinetic rate parameters are generally not available during early stages of drug discovery. Second, NS2B/NS3 proteases display complex conformational dynamics during function and inhibition, which is still poorly understood. This project aims to develop a new label-free single molecular approach to resolve the conformational states of NS2B/NS3 proteases. Key to the approach is the use of an innovative nanopore tweezers where the protease is confined with the pore lumen, allowing dynamic structural changes during substrate or inhibitor binding to be continuously monitored by current fluctuation signals. Analysis of the current traces will provide a complete profile of binding affinity and kinetic rates as well as the distribution of conformational states. Specifically, we will first build a nanopore tweezers tool set that is readily tunable for trapping various flaviviral proteases. Secondly, we will track and analyze the functional states of the NS2B/NS3 protease in the presence of various substrates. Influence of critical residues, substrate, construct design on the dynamic equilibrium between the “open” and “closed” states will be assessed to provide insight into the mechanism of protease activity. Finally, the nanopore tweezers will be deployed to determine the structural dynamics and binding thermodynamics and kinetics profiles of NS2B/NS3 interacting with various inhibitors. Once the inhibition profiles are established, the nanopore tweezers confined NS2B/NS3 system will be tested for screening a diverse compound library to identity novel allosteric inhibitors with improved drug-like properties compared to active-site inhibitors. This work will provide unprecedented kinetic information on the function- structural dynamics relationship of NS2B/NS3 complex and mechanisms of substrate binding and inhibition, as well as establish a new paradigm for high-throughput drug screening that is independent of enzymatic activity.",,2026,UNIVERSITY OF MASSACHUSETTS AMHERST,441244,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22098,3R01NS120895-03S1,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",37131,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22099,5R01NS120895-03,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",382697,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22100,5K08AI168569-02,Defining Molecular Epitopes of Protective Antibodies to Flaviviruses,"Project Summary/Abstract: The objective of this K08 Mentored Clinical Scientist Career Award Application is to provide Dr. Alena Markmann with a strong foundation in human immunology and the latest methods for studying human immune cells before launching her independent research career on the human immune response to RNA viruses. Dr. Markmann is an Assistant Professor of Medicine, tenure track, at the University of North Carolina -Chapel Hill (UNC) School of Medicine with a joint appointment in the Department of Microbiology and Immunology. The candidate has expertise in and a strong track record of publications on antibody structure, antibody-antigen interactions and antibody neutralization of viruses. By strengthening her knowledge of adaptive immunity to RNA viruses and mastering the latest methods for analyzing antigen specific B cells, Dr. Markmann will study how the human immune response to emerging flaviviruses like dengue and Zika can suppress viral infection and disease or enhance viral replication and exacerbate disease. The candidate and her mentor Dr. Aravinda de Silva have designed a training plan that includes a rigorous research component along with didactic instruction, networking and presentation opportunities, team management skills as well as manuscript writing and grantsmanship. Together these skills will establish the methods and principles necessary for successful career development. Flaviviruses are enveloped positive stranded RNA viruses that pose a growing threat to the human population and cause millions of infections annually. They are vector-borne, transmitted by ticks and mosquitoes, and cause a spectrum of disease manifestations including febrile illness, encephalitides that can cause lifelong complications, Congenital Zika Syndrome and dengue hemorrhagic fever and shock syndromes. For the most part, flaviviral infection result in a neutralizing protective antibody response against the infecting virus, that can last for years after infection. The four dengue viruses however are very similar antigenically and in many cases, result in generating a broad cross-neutralizing antibody responseto dengue virus serotypes that individuals have not yet been exposed to. Thus far, no one has identified the viral target site of these broadly neutralizing dengue antibodies that exist in the serum. Furthermore, though we know of a few major targets of the Zika protective antibody response from studying memory B cells, we do not know what the serum targets are. Preliminary results suggest that in the case of Zika serum antibody responses, binding targets are correlated with known strongly neutralizing memory B cell-derived antibody targets. Thus, we hypothesize in Aim 1, that serum antibody responses will mirror memory B cell responses, but will likely come from a smaller number of B cell clones and be less cross-reactive with other flaviviruses. In Aim 2 we will identify the viral binding targets of broadly cross- neutralizing dengue antibodies from the serum. These studies will result in the ident ification of critical protective viral targets to both dengue and Zika viruses from the serum antibody compartment in order to inform successful vaccine design.",,2027,UNIV OF NORTH CAROLINA CHAPEL HILL,195235,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22101,3R01NS120895-03S2,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2023,"RUTGERS, THE STATE UNIV OF N.J.",17286,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22102,1R01AI175435-01,Development of Inhibitors Targeting Flavivirus Methyltransferase,"Abstract: Flaviviruses are primarily insect-borne, associated with global morbidity and mortality, and found on every inhabited continent. Unfortunately, current therapeutic options for treating diseases associated with these viruses are limited. All flaviviruses encode methyltransferases (MTases)â€Â""flaviviral NS5 for both N-7 and 2'-O methylations of viral genomic RNA. The N-7 MTase function is essential for replication of the viral RNA genome, whereas 2'-O MTase function is required for the virus to evade the host innate immune response. These activities are conserved among the flaviviruses. For this project, our collaborative team will optimize the current lead compounds, perform high throughput screening (HTS) to identify additional lead candidates, chemically optimize the lead candidates, and define structure activity relationships. Optimizing current lead compounds using cutting- edge medicinal chemistry, the team will perform a large scale HTS campaign using innovative fluorescence chemical probes to identify additional small molecule inhibitors of flavivirus RNA capping MTases. We will perform an in-depth investigation of the model of action and antiviral efficacy using in vitro biochemistry, structural biology, virology, in vivo pharmacokinetics, and in vivo animal models, which will allow the development of novel, effective, broad-spectrum, and druglike therapeutic agents against both flaviviruses. Preliminary progress has been made in the identification of initial lead inhibitors of these MTases, demonstrating low nanomolar antiviral activity. We will advance these compounds to further develop potent antiviral compounds while conducting large- scale screening in parallel for additional structural scaffold discoveries. Complementary expertise among our investigators will synergize and expedite the progress of this research. Our collaborative objective is to provide first-in-class drug candidates for the treatment or prevention of these viral infections.",,2028,UNIVERSITY OF ARIZONA,767382,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P22103,5R35NS122310-03,Research Program Award (R35 Clinical Trial Optional) - Dr. Robyn Klein NINDS,"PROJECT SUMMARY/ABSTRACT Viral infections are now recognized as risk factors for diseases of progressive pathological forgetting, supporting a new paradigm in neuroimmunology whereby innate immune molecules that function as modulators of a variety of normal CNS functions induce neurodegenerative diseases during host-pathogen responses. Studying virus-mediated cognitive dysfunction through the multidisciplinary prism of immunology, neuroscience, and virology is critical for the identification of novel mechanisms of disease, discovery of neuroimaging tools and therapeutic treatments for a wide range of diseases of memory disorder. In my laboratory we made unanticipated, paradigm-shifting discoveries of the roles of CNS infiltrating mononuclear cells in microglial-mediated synapse elimination, disrupted adult neurogenesis, and generation of neurotoxic astrocytes using novel models of recovery from encephalitogenic flaviviruses, West Nile (WNV) and Zika (ZIKV) viruses. We identified classical complement proteins and cytokine receptor signaling as novel molecular mediators that regulate synapse elimination, neural stem cell (NSC) fates, neuron-microglia and microglia- astrocyte crosstalk within cortical structures that regulate memory formation and maintenance. We have also begun leveraging novel neuroimaging modalities to develop biomarkers that may be used to predict and monitor patients at risk for memory disorders. Our aim is to understand the mechanisms that induce alterations in synaptic connections and methods of repair that contribute to disruption of neuronal networks after recovery from viral infections. Our research program focuses on three broad areas related to the roles and regulation of innate immune molecules involved in spatial learning using novel murine models of post-infectious cognitive dysfunction. First, using genetic, pharmacologic and PET-MRI, we will identify and define molecular interactions between T cells and microglia or neurons that drive the generation and maintenance of resident memory T cells that promote cognitive dysfunction. We will use scRNAseq under BSL3 conditions to screen for genes and pathways to be targeted via cell-specific deletion of cytokine or chemokine receptors, or administration of agents that inhibit or enhance pathways. We will also develop diagnostic tools that employ ABSL3 PET-MRI. Second, we will define how microglia-astrocyte-NSC interactions in the context of recovery from CNS viral infections limit repair and recovery. We will use global and conditional gene targeting in mice to delineate the in vivo roles of cytokines in neural cell types that regulate astrocyte inflammasome activation and its relationship to neuronal and synapse recovery. We will also define innate immune mechanisms that direct and maintain astrogenosis during acute viral infection and recovery using PET-MRI detection of P2X7R, a marker of reactive astrocytes. Finally, will utilize reporter mice/fate mapping, bone marrow chimeras and scRNAseq to delineate the cytokine-mediated roles of myeloid cells in the generation of neurotoxic astrocytes during WNND recovery. Third, we will examine innate immune mechanisms triggered after viral infections that negatively impact cortical connectivity and determine whether neuroimaging can be used to predict and follow this process. Specifically, we will combine genetic approaches with functional optical intrinsic signal imaging of hemoglobin and calcium dynamics to define mechanisms that negatively impact cortical connectivity. Our research program will define new concepts in the molecular neuroimmunological regulation of synapses, T cell and glial interactions, inform studies of related processes throughout the nervous systems, and will likely enhance our understanding of neurodegenerative and other disorders of memory.",,2029,WASHINGTON UNIVERSITY,1181250,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22106,1R01AI168107-01A1,Control of influenza virus induced type I interferon signaling during pregnancy,"PROJECT SUMMARY/ABSTRACT Infectious insults are common during pregnancy; over the nine months of gestation ~60% of pregnant women self-report at least one illness, with viral upper respiratory tract (URT) infections being the most common. Although URT-trophic viruses replicate in the respiratory epithelium, the induced inflammatory cytokines like type I interferon (IFN) circulate systemically and can access the placenta. Recent work has shown that virally induced type I IFNs can be major drivers of adverse effects on fetal development. URT infections during pregnancy, however, are not typically linked to birth defects or miscarriage. It was therefore unclear why maternal infection with a pathogen like an influenza virus, which also induces to fetal IFN exposure, would not compromise fetal health. We hypothesized that an uncharacterized IFN regulatory pathway was the answer to this apparent discrepancy. By performing a genome-wide CRISPR/Cas screen, we identified a G-protein coupled estrogen receptor 1 (GPER1) dependent signaling pathway that protected fetal health from type I IFN signaling during maternal influenza A virus (IAV) infection. Disruption of this pathway led to fetal phenotypes as severe as those caused by direct congenital infections. Importantly, the activities of this pathway were restricted to reproductive and fetal tissues; alterations of its activity had no measurable effect on maternal health during IAV infection. The major goal of this application is to understand how GPER1-mediated signaling normally protects fetal health from inflammatory maternal cytokines such as type I IFN. In aim 1, we will define how GPER1-induced GPCR signaling suppresses IFN-induced JAK/STAT signaling and interferon-stimulated gene expression. These experiments will define a previously unknown mechanism for control of IFN signaling. In aim 2, we will characterize where and when GPER1 signaling is required to protect fetal health, as well as the effects of GPER1 dysregulation on cell physiology both in vivo and in primary human placental organoid cultures. These experiments will allow basic mechanistic insights into how maternal inflammation compromises fetal development. Finally, in aim 3, we will explore the consequences of IFN signaling on placental structure/function when GPER1 is absent and also evaluate the potential of hyper-activating GPER1 signaling under the inflammatory conditions that normally harm fetal development. Together, these studies will not only allow for a more complete understanding of IFN regulatory mechanisms and the fetal/maternal immune response but could also serve as the basis for an eventual first-in-class treatment designed to protect the fetus from inflammation without compromising maternal immunity.",,2027,DUKE UNIVERSITY,733813,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2022 +P22107,5K23AI168581-02,Arbovirus Prediction and Mitigation in the Indo-Pacific,"Project Summary / Abstract Dengue, a potentially life-threatening disease, has increased 30-fold in the last 50 years. In Indonesia, 1 in 3 children have had a dengue infection by 5 years old. Islands in the Indo-Pacific are highly vulnerable to climate change and water insecurity, two key drivers of arbovirus spread. Predicting and mitigating arbovirus transmission in the Indo-Pacific is critical to addressing the increasing risk of arboviruses in the U.S. In the next several decades, half the U.S. may have habitat suitable for Aedes aegypti and Ae. albopictus, mosquitos which spread dengue, chikungunya, Zika, and yellow fever viruses. Revitalizing Informal Settlements and their Environments (RISE) is a cluster randomized control trial evaluating the benefits of upgrading local water infrastructure in urban slums in Indonesia and Fiji. The RISE intervention is a prototype for future slum upgrading to address climate change and water insecurity throughout the Indo- Pacific. Although the World Health Organization recommends permanent environmental modification as an arbovirus control strategy, this has never before been rigorously tested. RISE provides an important opportunity to evaluate whether this model decreases or inadvertently increases arbovirus transmission. In addition to evaluating a new paradigm for mitigating arbovirus transmission, RISE is an ideal platform to assess gaps in knowledge about environmental drivers of arbovirus transmission. My hypothesis is that modifiable environmental conditions drive arbovirus transmission in these communities. To test this hypothesis, I will leverage the RISE platform to study arbovirus risk factors in this region and evaluate the impact of permanent environmental modification on arbovirus transmission in urban slums. I will also create a mathematical model to simulate arbovirus transmission in this region under a range of climate change and intervention scenarios. I have developed a customized career development plan that aligns with my proposed research. It incorporates both formal and informal training under the mentorship of Drs. LaBeaud and Luby. This training plan draws upon my existing expertise in global health, tropical medicine, and epidemiology; it will enhance my expertise in laboratory diagnostics, geospatial analysis, and mathematical modeling. The planned didactics and technical training included here will provide the foundation necessary to achieve my goal of becoming an academic physician focused on mitigating the spread of infectious diseases in the era of climate change.",,2027,STANFORD UNIVERSITY,193320,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector control strategies | Impact/ effectiveness of control measures,2022 +P22109,3R35GM147498-01S1,Modulating gene expression by RNA-targeting chimeras,"PROJECT SUMMARY RNA-binding small molecules have the potential to modulate the expression of genes whose protein products were previously considered “undruggable.” Risdiplam, targeting a precursor mRNA, was recently approved for the treatment of spinal muscular atrophy (SMA) and demonstrates the specificity and safety attainable by this approach. Although a variety of small-molecule scaffolds have been uncovered as RNA-binding ligands, their use is hampered by (1) lack of specificity and (2) unpredictable function. We propose a research program that will provide RNA-targeting chemical probes that will avoid these drawbacks. Inspired by Proteolysis Targeting Chimera (PROTAC) technology, we are designing chimeric molecules that will target RNA specifically and carry (deliver) the ability to induce RNA degradation or inhibit RNA translation, in a highly predictable manner. Our initial efforts towards an RNA-targeting chimera platform use a newly discovered RNA-binding coumarin derivative as a model and fine-tune its preferential binding properties through chemical modification. Through structural optimization, which includes using a “bidentate” RNA ligand strategy, we expect to achieve RNA-binding selectivity equal to or greater than that of oligonucleotides. At the same time, we propose to develop and optimize three novel effectors to precisely degrade RNA targets or inhibit the target RNA translation. These new effectors have shown promising results in inhibiting Zika virus (an RNA virus) gene expression. Ultimately, our proposed work will generate a top-down method for designing selective gene expression inhibitors that are independent of the gene's protein product. The long-term goal of our lab is to build a medicinal chemistry platform for making gene-specific and patient-specific therapies using RNA-binding small molecules. In this process, we will not only generate various tool compounds for studying important disease-modifying genes, but also combine computational and experimental technologies to understand the detailed mechanism of RNA-small molecule recognition.",,2027,UNIVERSITY OF KANSAS LAWRENCE,5095,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22110,3R35GM147498-02S1,Modulating gene expression by RNA-targeting chimeras,"PROJECT SUMMARY RNA-binding small molecules have the potential to modulate the expression of genes whose protein products were previously considered “undruggable.” Risdiplam, targeting a precursor mRNA, was recently approved for the treatment of spinal muscular atrophy (SMA) and demonstrates the specificity and safety attainable by this approach. Although a variety of small-molecule scaffolds have been uncovered as RNA-binding ligands, their use is hampered by (1) lack of specificity and (2) unpredictable function. We propose a research program that will provide RNA-targeting chemical probes that will avoid these drawbacks. Inspired by Proteolysis Targeting Chimera (PROTAC) technology, we are designing chimeric molecules that will target RNA specifically and carry (deliver) the ability to induce RNA degradation or inhibit RNA translation, in a highly predictable manner. Our initial efforts towards an RNA-targeting chimera platform use a newly discovered RNA-binding coumarin derivative as a model and fine-tune its preferential binding properties through chemical modification. Through structural optimization, which includes using a “bidentate” RNA ligand strategy, we expect to achieve RNA-binding selectivity equal to or greater than that of oligonucleotides. At the same time, we propose to develop and optimize three novel effectors to precisely degrade RNA targets or inhibit the target RNA translation. These new effectors have shown promising results in inhibiting Zika virus (an RNA virus) gene expression. Ultimately, our proposed work will generate a top-down method for designing selective gene expression inhibitors that are independent of the gene's protein product. The long-term goal of our lab is to build a medicinal chemistry platform for making gene-specific and patient-specific therapies using RNA-binding small molecules. In this process, we will not only generate various tool compounds for studying important disease-modifying genes, but also combine computational and experimental technologies to understand the detailed mechanism of RNA-small molecule recognition.",,2027,UNIVERSITY OF KANSAS LAWRENCE,61131,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22111,5R35GM147498-02,Modulating gene expression by RNA-targeting chimeras,"PROJECT SUMMARY RNA-binding small molecules have the potential to modulate the expression of genes whose protein products were previously considered “undruggable.” Risdiplam, targeting a precursor mRNA, was recently approved for the treatment of spinal muscular atrophy (SMA) and demonstrates the specificity and safety attainable by this approach. Although a variety of small-molecule scaffolds have been uncovered as RNA-binding ligands, their use is hampered by (1) lack of specificity and (2) unpredictable function. We propose a research program that will provide RNA-targeting chemical probes that will avoid these drawbacks. Inspired by Proteolysis Targeting Chimera (PROTAC) technology, we are designing chimeric molecules that will target RNA specifically and carry (deliver) the ability to induce RNA degradation or inhibit RNA translation, in a highly predictable manner. Our initial efforts towards an RNA-targeting chimera platform use a newly discovered RNA-binding coumarin derivative as a model and fine-tune its preferential binding properties through chemical modification. Through structural optimization, which includes using a “bidentate” RNA ligand strategy, we expect to achieve RNA-binding selectivity equal to or greater than that of oligonucleotides. At the same time, we propose to develop and optimize three novel effectors to precisely degrade RNA targets or inhibit the target RNA translation. These new effectors have shown promising results in inhibiting Zika virus (an RNA virus) gene expression. Ultimately, our proposed work will generate a top-down method for designing selective gene expression inhibitors that are independent of the gene's protein product. The long-term goal of our lab is to build a medicinal chemistry platform for making gene-specific and patient-specific therapies using RNA-binding small molecules. In this process, we will not only generate various tool compounds for studying important disease-modifying genes, but also combine computational and experimental technologies to understand the detailed mechanism of RNA-small molecule recognition.",,2027,UNIVERSITY OF KANSAS LAWRENCE,382500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22112,3R35GM147498-02S2,Modulating gene expression by RNA-targeting chimeras,"Project Summary RNA-binding small molecules have the potential to modulate the expression of genes whose protein products were previously considered “undruggable.” Risdiplam, targeting a precursor mRNA, was recently approved for the treatment of spinal muscular atrophy (SMA) and demonstrates the specificity and safety attainable by this approach. Although a variety of small-molecule scaffolds have been uncovered as RNA-binding ligands, their use is hampered by (1) lack of specificity and (2) unpredictable function. We propose a research program that will provide RNA-targeting chemical probes that will avoid these drawbacks. Inspired by Proteolysis Targeting Chimera (PROTAC) technology, we are designing chimeric molecules that will target RNA specifically and carry (deliver) the ability to induce RNA degradation or inhibit RNA translation, in a highly predictable manner. Our initial efforts towards an RNA-targeting chimera platform use a newly discovered RNA-binding coumarin derivative as a model and fine-tune its preferential binding properties through chemical modification. Through structural optimization, which includes using a “bidentate” RNA ligand strategy, we expect to achieve RNA- binding selectivity equal to or greater than that of oligonucleotides. At the same time, we propose to develop and optimize three novel effectors to precisely degrade RNA targets or inhibit the target RNA translation. These new effectors have shown promising results in inhibiting Zika virus (an RNA virus) gene expression. Ultimately, our proposed work will generate a top-down method for designing selective gene expression inhibitors that are independent of the gene's protein product. The long-term goal of our lab is to build a medicinal chemistry platform for making gene-specific and patient-specific therapies using RNA-binding small molecules. In this process, we will not only generate various tool compounds for studying important disease- modifying genes, but also combine computational and experimental technologies to understand the detailed mechanism of RNA-small molecule recognition.",,2027,UNIVERSITY OF KANSAS LAWRENCE,144703,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22116,5D43TW012246-02,Training and Research on Arboviruses and Zoonoses In Nigeria and Sierra Leone (TRAIN),"ABSTRACT Emerging viral diseases comprise several of the greatest global risks to human health, and West Africa is a source and epicenter for several. These include arthropod-borne viruses (arboviruses), such as chikungunya, Zika, and yellow fever with African origin and both ancient and recent histories of spread to Asia and the Americas to initiate massive epidemics. Dengue also increasingly recognized in Africa as a major public health problem. Zoonotic African hemorrhagic viruses also caused unprecedented outbreaks during the past decade. In 2014, the first West African epidemic of hemorrhagic fever attributed to Ebola virus spread to several countries including Sierra Leone, representing by far the most devastating filoviral outbreak on record with over 11,000 fatalities. Lassa virus, causing an estimated 100,000-300,000 hemorrhagic fever cases in Africa annually, produced an unprecedented 2018-2019 epidemic in Nigeria. The mechanisms whereby these zoonotic viruses emerge remain obscure along with understanding of their true disease burden and varied clinical disease and sequelae outcomes. To address these challenges, we will develop a new generation of West African scientists to predict, prevent and contain emerging viral diseases through multidisciplinary scientific and public health training. Leveraging our West African Center for Emerging Infectious Diseases (WAC-EID, NIAID U01AI151801), outstanding research leaders in West Africa, and the exceptional breadth of expertise in emerging viral diseases at the University of Texas Medical Branch (UTMB), we will provide multidisciplinary training for young scientists from two leading universities: Njala University in Sierra Leone and Jos University in Nigeria. The aims of Training and Research on Arboviruses and Zoonoses In Nigeria and Sierra Leone (TRAIN) include: 1. Provide general on-site training at Njala and Jos Universities to Master’s/PhD students enrolled in the local graduate programs; 2. Provide specialized training at UTMB on the most advanced methods and techniques for expertise transfer to Sierra Leone and Nigeria; 3. Provide on-site research training at Njala and Jos Universities to ensure successful local implementation of the program, which will include education of laboratory technicians/managers among others; 4. Integrate trainees into the WAC-EID’s research programs to gain hands-on experience in surveillance activities, diagnostics and data management. Five trainees per year will participate in short-, medium-, and long- term training phases at UTMB and in W. Africa. Training activities will include didactic courses, online modules, field training, molecular/virological techniques including the study of animal models and pathogenesis, biosafety training, and lab management education. Upon the completion of our training program, these young scientists will play critical roles in surveillance to better understand the circulation of emerging viruses in the region, mechanisms of emergence, virus discovery, epidemic transmission, pathogenesis, and countermeasures to mitigate emerging viral threats. The local training programs are designed to be sustainable, and the 3-way research and training partnerships will broadly benefit science and public health throughout the region.",,2027,UNIVERSITY OF TEXAS MED BR GALVESTON,248400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22118,5R01AI154844-03,Essential early events in the flavivirus lifecycle,"Project Summary Arthropod-borne flaviviruses such as dengue virus, West Nile virus, yellow fever virus (YFV), and Zika virus, are a major cause of human disease. We are studying the early, post-fusion and pre-replication events in the flavivirus lifecycle by using the prototype flavivirus, YFV, as our model. Our overarching hypothesis is that flaviviruses, which alternately replicate in vertebrate and invertebrate hosts, have evolved to use i) highly conserved factors shared between hosts; and ii) multiple, redundant factors that may not be well conserved between hosts. Therefore, discoveries made with YFV will be validated and studied by comparison to other flaviviruses and between human and mosquito cells. Aim 1 focuses on the post-fusion process of nucleocapsid uncoating, dissecting the mechanisms by which cells unlock this fateful cargo. Aim 1 is a logical extension of our Preliminary Data showing that the delivery of a translatable YFV genome requires cellular ubiquitylation and VCP/p97, a cellular ATPase that extracts ubiquitylated proteins from large macromolecular complexes. Aim 2 focuses on identifying the cellular protease(s) that cleave the viral NS1-2A polyprotein intermediate. Cleavage is essential for flavivirus replication (shown here), yet the identity of this protease has remained elusive for over two decades. We have identified a small family of related candidate NS1-2A proteases and are validating their activity by rigorous, combinatorial genetic ablation. These efforts will solve long- standing puzzles in flavivirus gene expression and replication and identify targets for future development of broadly acting antivirals.",,2026,YALE UNIVERSITY,418750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22119,5U01AI151807-04,Coordinating Research on Emerging Arboviral Threats Encoing the Neotropics (CREATE-NEO),"Project Summary In recent decades, Central and South America have experienced spillover of endemic arthropod-borne viruses (arboviruses) from wildlife reservoirs into humans, exchange and recombination of emerging arboviruses within the region, resurgence of arboviruses previously controlled by vaccination or vector control, introduction and spread of novel arboviruses, and exportation of viruses to other regions. Furthermore, there is great concern that newly-introduced Zika virus may spill back into an enzootic transmission cycle in the Americas. Central and South America encompass enormous vertebrate and invertebrate biodiversity, and these species harbor a broad range of arboviruses whose risk of spillover and spread in humans is presently unknown. Increases in the rates of global travel, invasion of novel vector species, urban expansion, deforestation, and global climate change all elevate the risk of further arbovirus emergence, as does the breakdown of public health structures in Venezuela. The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE- NEO) project will provide a network of surveillance sites in the neotropics coupled to cutting-edge modeling approaches in order to anticipate and counter emerging arboviruses. Aim 1 will identify novel and known arboviruses as well as the host-vector networks that sustain transmission of these viruses within the neotropics, map the spatial distribution of these transmission networks, and characterize virus transmission dynamics within these networks. To do so, we will collect mosquitoes and other vectors as well as non-human primates and other vertebrate hosts at multiple sites in areas of high and varied biodiversity in Panama and Brazil and screen these samples for known and novel arboviruses. These data will then be analyzed using niche modeling, machine learning to predict undiscovered hosts and vectors, and dynamical transmission models. Aim 2 will focus on prospective and retrospective analysis of human infection and disease. To do so, we will leverage ongoing human clinical cohorts at multiple sites in Brazil and Panama. We will extend and expand these cohorts, with a particular focus on the immune-mediated interactions among multiple arboviruses at sites of hyperendemicity. We will also develop novel diagnostics to capture known and novel arboviruses and model the impact of human and non-human primate movement on spillover and spillback of target arboviruses. Data and models generated via these two aims will forewarn local, regional and global public health agencies of arboviruses within Central and South America that pose particularly high risk of spillover, emergence into transmission among humans, and/or international spread. Moreover CREATE-NEO will build local capacity to predict, detect and respond to emerging arboviruses at their point of origin, thereby maximizing the potential to avert full-blown emergence.",,2025,UNIVERSITY OF TEXAS MED BR GALVESTON,1544479,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Immunity | Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping,2020 +P22120,1R21AI174052-01,Haplotype-resolved genome assemblies and chromosomal rearrangements in arboviral vector Aedes albopictus,"PROJECT SUMMARY The Asian tiger mosquito Aedes albopictus is native to Southeast Asia but in a few decades this species expanded its range to all continents except Antarctica. Aedes albopictus is capable of transmitting multiple arboviruses including dengueâ€Â""the leading arboviral disease of 21st centuryâ€Â""Chikungunya, and Zikaâ€Â""an emerging health threats for the world. Because of its remarkable ability to develop a photoperiodic diapause in the temperate climate, Ae. albopictus has the potential to spread these dangerous diseases further north. This project will develop haplotype-resolved chromosome-scale genome assemblies for multiple strains of Ae. albopictus and will test if adaptations to the temperate climate are associated with chromosomal rearrangements in this mosquito. Toward this end, we propose the following specific aims: 1) develop a haplotype-resolved chromosome-scale genome assemblies for four strains of Ae. albopictus including the Foshan strain; 2) improve the physical genome map for the Foshan strain of Ae. albopictus; and 3) identify chromosomal rearrangements in different populations of Ae. albopictus world-wide. Our long- term goal is to understand the genetic basis of the incredible phenotypic plasticity of Ae. albopictus that helps this mosquito to rapidly spread around the globe. We envision that the availability of the high-quality reference genome assemblies for multiple strains of Ae. albopictus will stimulate further genetic studies aimed at preventing mosquito-borne disease transmission.",,2024,VIRGINIA POLYTECHNIC INST AND ST UNIV,227056,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22121,5R21AI166633-02,Influence of sleep-like states on mosquito behavior and physiology,"Project summary Sleep is critical for nearly all animals. This state is characterized by a specific set of parameters for each species however there is a lack of sleep-based studies in mosquitoes. This should be considered a major knowledge gap in mosquito biology and potentially hinders the development of new control methods and our understanding of factors influencing vectorial capacity. Our preliminary studies suggest that there will likely be explicit factors underlying mosquito sleep, which need to be fully characterized to define this biological state in mosquitoes. The focus of the proposed work is to provide the first extensive characterization of mosquito sleep. After sleep has been defind, studies on the manipulation of sleep will discern how reduced sleep (e.g., induced by human activity in urban areas) may alter behavioral and physiological aspects of mosquitoes such as host preference, blood- feeding, reproductive output, and viral transmission. These studies are supported by the following: 1) Historic and our preliminary observations of putative sleep postures of mosquitoes, 2) Initial activity monitoring results that establish that day and night active mosquitoes sleep at higher rates during the night and day, respectively, 3) targeted studies suggesting that sleep can be prevented by mechanical disturbance that impacts subsequent host landing, 4) Preliminary data showing a reduction of spontaneous neural activity after prolonged rest, 5) Our development of novel sensory deprivation equipment that allows for mosquito observation without host interference to pinpoint differences that could be related to mosquito sleep-like states, and 6) Integrative and innovative experimental design that ranges from basic behavioral analyses to neuronal recording that will provide an encompassing view of the mosquito sleep state. This study has two specific aims: Specific Aim 1. Establishing the characteristics associated with sleep-like states in mosquitoes. Specific Aim 2. Defining shifts in mosquito fitness, behavior, and viral transmission following sleep deprivation. Upon completion of these specific aims, our expected outcomes are to have defined sleep-like states in mosquitoes and, subsequently, how sleep deprivation impacts a range of epidemiologically relevant biological aspects. This will be transformative to the research field and will set the stage for multiple lines of research. Most importantly, these studies will create a novel paradigm, where aspects of mosquito biology should be measured under two independent periods: a non-resting (no sleep) and sleep-like status. Finally, our anticipated results are likely to inform on the adaptations of mosquitoes to urban areas where host activity patterns and light/dark conditions are decoupled from day/night successions and could impact sleep, mosquito-host interactions, and potentially patterns of disease transmission.",,2024,UNIVERSITY OF CINCINNATI,226819,Disease Vectors,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22122,5R21AI168716-02,Conserved molecular mechanisms of replication for mosquito-borne flaviviruses,"As obligate intracellular parasites, all viruses replicate by coopting host machinery through virus-host protein interactions. Arthropod-borne viruses, which are transmitted to vertebrates by arthropod vectors, must hijack host machinery in human and arthropod cells to accomplish the same fundamental aspects of virus replication. Thus, arthropod-borne viruses maintain protein interactions with host homologs (interologs) to replicate. Identifying these interologs is critical to understanding how an important group of viruses deals with this unique constraint from a biophysical perspective. For flaviviruses transmitted by Aedes mosquitoes (Aedes-borne flaviviruses), it can also inform therapy development by expanding the list of drug targets since these viruses are a major source of human disease. Using a comparative proteomics approach, we recently found large-scale evidence of interologs for dengue virus (DENV), a major Aedes-borne flavivirus that infects nearly 400 million people annually. These interologs involve processes that are essential for virus replication in human and Aedes cells. We hypothesize that Aedes-borne flaviviruses use the conserved interologs to facilitate replication in human and Aedes cells due to the similar constraints place on these viruses and the complexity of maintaining virus-host protein interactions across multiple divergent hosts. The overall objective of this proposal is to systematically compare the role of interologs in virus replication for two Aedes-borne flaviviruses. We will focus on DENV to take advantage of our existing interolog data and yellow fever virus (YFV), a re-emerging Aedes-borne flavivirus that is distantly related to DENV. In Aim 1, we will systematically identify YFV-human and YFV-Aedes protein interactions using affinity purification and mass spectrometry. We will further identify YFV interologs through computational network integration. In Aim 2, we will identify interologs conserved between YFV and DENV using a similar computational network integration approach. We will then test the role of interologs in Aedes-borne flavivirus replication by measuring virus replication following interolog knockdown. This work will identify the conserved molecular mechanisms by which a medically important group of viruses replicates. It will reveal the biophysical parameters that constrain virus evolution. In the future, the interologs we identify could be leveraged as pharmacological or vector engineering targets to inhibit replication of multiple Aedes-borne flaviviruses. Our work would also lay the foundation to search for more interologs conserved across different arthropod vectors and/or different virus families.",,2025,UNIVERSITY OF CALIFORNIA AT DAVIS,240331,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P22123,5R01AI151166-04,Metabolic basis of mosquito-endosymbiont-virus interactions,"PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.",,2025,COLORADO STATE UNIVERSITY,531514,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22124,75N93019C00062-P00020-9999-1,"B Cell Epitope Discovery and Mechanisms of Antibody Protection: Responses to Dengue 4, Powassan, Chikungunya, and Venezuelan Equine Encephalitis Viruses ","This contract supports the identification of human B cell epitopes derived from four viral pathogens; Dengue virus 4, Powassan virus, Chikungunya virus, and Venezuelan equine encephalitis virus, combined with basic studies to understand protective immunity mediated by antibodies, as well as pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. The primary goal of this contract is the delineation of B cell epitopes recognized by potently neutralizing or protective antibodies and evaluation of correlates of protection that can aid in the development of vaccines and therapeutics against select arthropod-transmitted viruses. The Contractor has chosen two flaviviruses (Dengue virus 4 and Powassan virus) and two alphaviruses (Chikungunya virus and Venezuelan equine encephalitis) for primary investigation of antibody responses to viral glycoprotein antigens. The Contractor will also evaluate protective antibodies that recognize the flavivirus nonstructural protein 1 (NS1) produced by West Nile and Zika viruses.",,2024,WASHINGTON UNIVERSITY,1671692,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P22128,7R01AI133348-07,Mechanisms of viral RNA maturation by co-opting cellular exonucleases,"PROJECT SUMMARY Flaviviruses are single-stranded positive-sense RNA viruses that include dangerous human pathogens like dengue, West Nile, Yellow Fever, Zika, and many others. During infection, these viruses produce a set of non- coding RNAs called ‘subgenomic flavivirus RNAs’ (sfRNAs) that interact with cellular proteins to manipulate the cellular environment, to include inhibiting the antiviral response. sfRNAs have been directly linked to cytopathic and pathogenic outcomes, and viruses that cannot produce sfRNAs are attenuated, motivating efforts to understand the mechanism of xrRNA production. sfRNAs are made when cellular 5’à3’ exoribonucleases (in particular, Xrn1) processively degrade the viral genomic RNA but then halt at specifically structured RNA elements in the viral 3’ UTR called exoribonuclease resistant RNAs (xrRNAs). By solving the structures of multiple xrRNAs by x-ray crystallography and combining this with biochemistry, biophysics, and virology, we showed that xrRNAs fold into a unique ring-like topology that creates a mechanical block the exoribonuclease cannot pass through. Furthermore, we used our discoveries to classify xrRNAs and to find new examples associated with both non-coding and coding RNAs. These successes now define several new questions. First, xrRNAs are often found in multiple copies ‘in tandem’ where their function is coupled in some way, but the structural basis of this coupling, and the effects of breaking the coupling on both sfRNA formation and viral infection kinetics, are unknown. Second, although we have a good understanding of several classes of xrRNAs, we have yet to solve the structure of an xrRNA from a tick-borne flavivirus, which appear to have interesting and unique properties. Third, although we have found many new examples of xrRNAs, it appears there are many more that are undiscovered, and we also do not understand how the various classes of xrRNA relate evolutionarily. How do these structures diversify and evolve in 3-D given the tight constraints on their folding? Here, we propose to answer these questions in three aims, employing a strategy that combines biochemistry, x- ray crystallography, cryo-EM, virology, and in vitro selections coupled with computational tools. The research described here will contribute significant basic knowledge regarding an important molecular process of broad applicability to viral disease, a necessary step between the discovery of a mechanism and the targeting of it for therapeutic intervention.",,2027,NEW YORK STRUCTURAL BIOLOGY CENTER,534584,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P22130,5R01AI157491-04,Sex ratio distortion in Aedes aegypti,"Project Summary Aedes aegypti is a major vector of dengue, chikungunya, and Zika viruses. The global incidence of dengue has increased dramatically in recent decades. The first dengue vaccine, DengvaxiaÃ'®, is recommended for a very limited population. Current prevention depends mainly on effective vector control, which is hindered by increasing insecticide-resistance. Novel genetic strategies for vector control are actively explored, including both population suppression and population replacement. Recent field releases of either transgenic and Wolbachia-infected sterile male mosquitoes show promising results for suppressing Aedes populations in areas of modest size. Given the biological, geographical, economic and cultural complexity facing global mosquito-borne infectious disease control programs, diverse measures that can be integrated to address various challenges are urgently needed. Female to male sex ratio distortion is an attractive concept for developing new control measures, as females are responsible for disease transmission and population growth. Aedes and Culex mosquitoes contain homomorphic sex- determining chromosomes and maleness is conferred by a dominant male-determining factor (M factor) within an M locus that is on one of a pair of chromosome 1. Male-biased sex-ratio distortion occurs in natural populations in Ae. aegypti, which is associated with m-chromosome breakage during meiosis at a few sites. The Distorter locus is linked to the M-locus on the M-chromosome, conferring a meiotic drive as it increases the probability of its own inheritance. We recently discovered the M factor, an RNA-binding protein named Nix and identified the M and m locus in Ae. aegypti. By analysing male and female Illumina reads across a few strains, we found a number of m-specific repeats that can be targeted for breakage by CRISPR/cas9 during male meiosis, potentially leading to a male-biased sex ratio distortion. We will pursue the following specific aims: 1) Systematically characterize components to develop m-shredders. Research performed here will also improve our understanding of the male germline and the homomorphic sex chromosomes and facilitate any future genetic manipulations involving the male germline. 2) Develop m-shredder lines with various degrees of M-linkage to optimize effective population suppression. 3) Model various applications of m-shredders in population suppression and transgene recall. In summary, innovative technologies will be used to gain fundamental insights into male germline expression and the differentiation of the homomorphic sex chromosomes of Ae. aegypti. m-shredders with various levels of efficiency and transmissibility will be developed and modelled for population suppression and transgene recall, expanding the tool box for integrated vector management. 1",,2025,VIRGINIA POLYTECHNIC INST AND ST UNIV,566550,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22131,5R00DC019401-04,Elucidating the structural determinants of odor specificity in insect olfactory receptors,"Project Summary The sense of smell provides animals with vital information about their environment. At the molecular level, olfactory stimuli consist of thousands of distinct small molecules that share no common chemical feature other than being volatile. To contend with this diversity, insects and mammals alike have evolved large families of olfactory receptors (ORs) that operate in a combinatorial way, whereby some receptors are broadly activated by many different odorants and others are exquisitely tuned to a specific compound. The molecular mechanisms that endow ORs with such diverse ligand-binding properties remain unknown, largely because the isolation and structural characterization of ORs has been a decades-long technological challenge. Using cryo-electron microscopy, I recently determined the first atomic-resolution structure of an insect OR bound to an odor. By determining the structures of additional insect ORs with broad and specific ligand-binding properties, the proposed research project will elucidate the molecular mechanism of odor detection and discrimination. To this end, the K99 mentored phase (Aim 1) will reveal the atomic structures of two primitive insect ORs with different ligand specificities unbound and in complex with multiple odor ligands, shedding light on the molecular determinants that underlie broad or specific odor selectivity. Next, the R00 independent phase (Aim 2) will focus on ORs from disease-carrying mosquitoes that participate in human host-seeking. These ORs exhibit small polymorphisms that drastically affect their ability to detect human odors. Elucidation of the atomic structure of these mosquito ORs bound to human volatiles will illuminate the molecular properties that enable mosquitoes to detect and prey on humans. Together, this research program will lend fundamental insight into the normal function of sensory processing of olfactory information. Additionally, as insect ORs are critically involved in human host-seeking that facilitates the spread of insect-borne diseases, this work will provide a foundation for the development of novel insect repellents that could curb diseases such as malaria, Zika, and dengue fever. The proposed development plan complements my training in structural biology and biophysics with computational modeling of receptor-ligand interactions and in vivo assays in Drosophila. At the end of the mentored phase, I will be equipped with the necessary tools to conduct comprehensive structural and functional studies of odor detection and discrimination by insect vectors of disease. To achieve these goals, I will take advantage of the extensive resources of the Rockefeller University, the mentorship of Dr. Vanessa Ruta and the appointment of an Advisory Committee that will lend expertise in key aspects of the project and career development. Additionally, with the support and resources from the MOSAIC/UE5 network I will expand my mentorship and leadership skills to successfully transition to an independent position while continuing my ongoing efforts to enhance diversity in the biomedical workforce.",,2025,HARVARD MEDICAL SCHOOL,249000,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector control strategies",2021 +P22132,5R01HL153073-04,Transfusion-related immunomodulation influences infectious disease outcomes,"Project Summary/Abstract Transmission of acute viral infections through blood transfusion during large epidemics is a serious public health issue, particularly for newly emerging infections for which no sensitive FDA-approved tests are available. Arboviruses can be serious acute infections leading to serious long-term complications, and are noted for their massive epidemic, as recently demonstrated with first chikungunya virus (CHIKV) and then Zika virus. Despite possessing many of the characteristics required for blood transfusion transmission (TT), such as high loads of infectious virus in blood and the ability to infect via intravenous inoculation, there have never been any CHIKV TT events reported. This is despite large-scale epidemics where up to 2% of blood donations have been found to be RNA reactive. We have preliminary data supporting the fact that CHIKV can be transfusion-transmitted in mice, and that transfusion of RBC attenuated CHIKV pathogenesis. The central hypothesis behind this study is that TT does occur, however a number of factors drive infection towards being asymptomatic or mild. Further, immune modulation during transmission, in this case via the blood transfusion itself, leads to an attenuation of disease. Specifically, we and others have demonstrated a number of innate immune factors are both modulated by transfusion and able to alter CHIKV outcomes. These include innate lymphoid cells and regulatory T cells and the cytokines both upstream and downstream of their stimulation. This study will use a murine model of CHIKV pathogenesis to investigate these findings further. Additionally, it will mimic blood transfusions, TT of CHIKV, and study immune parameters and disease outcomes. Beyond understanding the interplay between pathogenesis and blood transfusion, these studies will have a wider impact on acute viral infections in general. It is likely that similar immune factors can have dramatic effects on viral replication and/or pathogenesis, and thus a deeper understanding of how these mechanisms are mediated will allow better planning for screening efforts and potentially even interventions during serious epidemics. This will allow improved capabilities and decision making in responding rapidly to a new viral threat to blood safety and availability.",,2024,VITALANT,623056,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P22135,1F31AI176728-01,Investigating the Formation and Function of Subgenomic Flavivirus RNAs During Flavivirus Infection of the Mosquito Vector,"Project Summary: During infection by arthropod borne flaviviruses such as Dengue (DV) and Zika (ZV), infected cells accumulate non-coding RNAs termed Subgenomic Flaviviral RNAs (sfRNAs) that consist of the viral genomic RNA’s 3ïÂ'¢ untranslated region (UTR). sfRNAs are generated when the host 5ïÂ'¢ to 3ïÂ'¢ exoribonuclease Xrn1 encounters exoribonuclease-resistant RNA (xrRNAs) structures in the genome’s 3ïÂ'¢ UTR that halt its progress. Analysis of flaviviral genomes has revealed that the majority of mosquito-borne flaviviruses have multiple xrRNAs “in tandem”. It was hypothesized that these structures were functionally redundant and working independently to generate sfRNA. However, data in our lab has revealed that within certain flaviviruses the structural integrity of one xrRNA is sensed by the other, affecting its function. We hypothesize that this “coupling” or “coordination” is due to tandem xrRNAs interacting through intervening sequences and/or structures. To test this hypothesis, we developed a surrogate reporter system that allows us to test the functional effects of mutations in the intervening sequence of the Dengue virus tandem xrRNAs. Specifically, our assay reports on changes in the patterns of produced sfRNAs, which have been well characterized for the wild type sequences. For aim 1 we will use this system to explore the mechanism of this coupling between xrRNAs in multiple flaviviruses. In addition, this research will also include uncovering the mechanism in which sfRNAs interfere with the mosquito immune response. Specifically, it has been shown that sfRNAs are capable of interacting with the mammalian Dicer protein, reducing the amount of small interfering RNA (siRNA) formed in vitro. Since mosquitos rely on RNA interference (RNAi) as their primary defense against viral infection, and mammalian and mosquito Dicer proteins are well conserved, we hypothesize that sfRNAs dampen the RNAi response in mosquitos by interacting with the Dicer-2 (Dcr2) protein of the mosquito RNAi pathway. Under aim 2 we will utilize a series of in vitro biochemical assays to test how this interaction between sfRNA and Dcr2 is taking place and elucidate on how sfRNAs work to dampen the immune response of the mosquito vector. Uncovering the dynamics of these host pathogen interactions could lead to new strategies for attenuating sfRNA production in mosquitos to curb the spread of flaviviruses.",,2026,UNIVERSITY OF COLORADO DENVER,36476,Disease Vectors | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Vector biology",2023 +P22136,1R13AI172249-01,"Infections in Pregnancy: PathogenicMechanisms, Experimental Advances and Clinical Strategies","ABSTRACT Support is requested for a Keystone Symposia conference entitled Infections in Pregnancy: Pathogenic Mechanisms, Experimental Advances and Clinical Strategies, organized by Drs. Helen Lazear, Carolyn Coyne and David Aronoff. The conference will be held in Santa Fe, New Mexico from January 22-25, 2023. The placenta generally provides a robust barrier to the fetal compartment across which relatively few microbes are able to penetrate, and functions together with other defenses at the maternal-fetal interface to protect against congenital infections. Nonetheless, congenital pathogens including human cytomegalovirus, Zika virus, Toxoplasma gondii, and group B streptococcus can cause fetal loss, growth restriction, birth defects, and developmental delays. The list of congenital pathogens continues to grow; for example, the recently emergent virus SARS-CoV-2, can cause devastating adverse pregnancy outcomes independent of vertical transmission. In addition to pathogenic effects on the fetus and neonate, infections during pregnancy can have distinct impacts on maternal health, owing to the physiologic and immunologic effects of pregnancy. As such, there is a need to better understand the pathogenic mechanisms of congenital infections and immune defenses at the maternal-fetal interface, as well as to develop improved vaccine, treatment, and diagnostic strategies to combat congenital infections. But in many cases these infections can be difficult to study due to limitations in experimental systems and challenges in designing studies with human patients. This Keystone Symposia conference will bring together researchers investigating infections in pregnancy from a range of perspectives including basic biology, pathogenesis models, clinical studies, and patient care. The program is designed to highlight the new advances in understanding the pathogenic mechanisms of congenital infections. Other sessions will share recent developments in experimental systems for studying congenital infections, in addition to providing details on the latest developments in vaccines, therapeutics, and diagnostics. The program will also be designed to consider the effects of infections during pregnancy on maternal health, as well as on fetal, infant, and child health. This conference will provide an opportunity for researchers from diverse backgrounds to exchange ideas and develop new collaborations to promote future research on infections during pregnancy. Finally, this conference is being paired with another Keystone Symposia meeting on Maternal-Fetal Crosstalk. This will allow participants at both conference the chance to network and develop new collaborations through shared sessions and meals.",,2023,KEYSTONE SYMPOSIA,10000,Other | Not applicable,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Other,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2023 +P22140,5R21AI167849-02,How can mosquitoes develop and reproduce in the complete absence of juvenile hormone?,"PROJECT SUMMARY Recent dramatic increases in the incidence of mosquito-borne diseases, like Malaria, Zika, Chikungunya and Dengue Fever, and the wide-spread resistance of mosquitoes to insecticides emphasizes the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on continued basic research on the biology of mosquitoes. Juvenile hormone (JH), an epoxidated sesquiterpenoid, is an essential regulator of major developmental and life history events in insects. Insects and crustaceans originated from aquatic pancrustacean ancestors that invaded terrestrial ecosystems over 450 million years ago. The Methoprene-tolerant (Met) protein is the intracellular receptor for insect JHs. The ability of Met to respond to MF, the “crustacean JH”, suggests that the role of Met in sesquiterpenoid signaling precedes the evolutionary separation of the hexapoda from the crustacean lineages. To address the evolutionary and biological significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, the methyl transferase (JHAMT) and the P450 epoxidase CYP15 (EPOX). jhamt-/- larvae lacking both MF and JH died at the onset of metamorphosis. While epox-/- mutants, which synthesized MF but no JH completed the entire life cycle. While epox-/- adults are fertile, the reproductive performance of both sexes is dramatically reduced. Using these two lines of null mutant mosquitoes, we will investigate how in the absence of JH, MF is sufficient to complete adult development. Our hypothesis is MF is able to properly activate the gene networks that control mosquito larval development and metamorphosis. Additionally, we will investigate the reproductive fitness cost in JH null females. We expect to recognize the molecular mechanism underlying the differences in JH signaling in our three model lines (jhamt-/-, epox-/- and WT). Our two null mutant mosquito lines provide a unique opportunity to explore the role of non-epoxidated versus epoxidated JHs in the development and reproduction of insects. Completing the proposed research could lead to the identification of targets for designing new, specific and affordable strategies suitable for mosquito control.",,2024,FLORIDA INTERNATIONAL UNIVERSITY,147500,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2022 +P22141,5R01AI151004-04,Precision guided SIT for the control of vector-borne disease,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases. Dengue alone causes 90 million infections per year globally and like many vector-borne diseases, currently there are no drugs or vaccines to treat or prevent these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. In recent years, novel vector population suppression technologies have been created (e.g. RIDL and Wolbachia based systems), but production of mosquitoes for these programs is labor intensive and is limited in scalability and distribution. In this study, we will use a functional genomic screening approach to identify key sex determinate, female essential (FE) and male fertility (MF) genes in the dengue vector, Ae. aegypti. These studies will improve our understanding of the biology of this important vector and it can be used to inform the design of new genetic population suppression methods to control this vector. After these genes are identified and characterized, we will incorporate them into the design of precision guided sterile insect technique (pgSIT) technologies in an attempt to overcome limitations in traditional SIT control strategies. Sterile insect technique (SIT) is the gold standard for insect population control but has many limitations. Our proposed technology aims to simultaneously knock-out FE and MF genes using a binary CRISPR/Cas9 system in the Ae. aegypti disease vector. One line will target one or more female essential FE genes and one or more MF genes and the other line will express a Cas9. When these two lines are crossed, they create sterile, male progeny that are ready for release into a population suppression program. To generate these lines, initially we will characterize >40 candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be determined over many generations to ensure population stability. The design and integration of these transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression systems, including the impact of transgene expression timing and transgene location on the long-term stability of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies. In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",461949,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P22142,5R25AI147391-04,Summer Institute in Statistics and Modeling in Infectious Diseases,"ABSTRACT The overall goal of the annual Summer Institute in Statistics and Modeling in Infectious Diseases (SISMID) at the University of Washington is to educate the next generation of researchers in a broad range of state-of-the-art quantitative methods for infectious disease research. Courses for skill development: SISMID is a collection of 16 2.5-day modules offered over 2.5 weeks in July on a variety of topics relevant to research education in statistics, modeling and computational methods applied to infectious diseases. Most participants take on average three modules per year. SISMID has been held each summer since 2009. This proposal requests funds for 2020-2024. The 2020 SISMID proposes to offer the following: 1. Probability and Statistical Inference; 2. Mathematical Models of Infectious Diseases; 3. Introduction to R; 4. Causal Inference; 5. Evolutionary Dynamics and Molecular Epidemiology of Viruses; 6. Stochastic Epidemic Models with Inference; 7. Markov chain Monte Carlo I; 8. Microbiome Data Analysis; 9. Pathogen Evolution, Selection, and Immunity; 10. Simulation-based Inference for Epidemiologic Dynamics; 11. Statistics and Modeling with Novel Data Streams; 12. Infectious Diseases, Immunology, Within Host Models; 13. Markov chain Monte Carlo II for Infectious Diseases; 14. Spatial Statistics in Epidemiology and Public Health; 15. Contact Network Epidemiology: 16. Reconstructing Transmission with Genomic Data. The instructors are drawn from the University of Washington and other academic institutions in the USA and Europe, and industry. Instructor mentors will be assigned to recipients of support through this grant and put into email contact before SISMID. They will meet together during SISMID. Research experiences will include teams working on ongoing projects and using innovative methods for reproducible research. This NIAID Research Education Program (R25) will allow us to provide graduate students and postdoctoral fellows approximately 350 modules per year without charge and 100 partial travel awards.",,2025,UNIVERSITY OF WASHINGTON,330891,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P22143,5U01AI151788-04,American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES),"ABSTRACT Recent pandemics of human pathogens have revealed the limitations of current surveillance systems. The sequential arboviral epidemics in the Americas showed how outbreak detection can be delayed and opportunities missed to collect well-characterized specimens and data for surveillance, basic science, clinical research, and development of vaccines and new diagnostics. In response, we have assembled a consortium of world-renowned investigators in arbovirology, epidemiology, immunology, viral diagnostics, phylogenetics, and clinical research, while leveraging research infrastructure and expertise in long-term cohort and hospital-based studies. This has resulted from 3 decades of collaborative international research, with over 200 joint publications, and extensive experience in preparing for and responding to outbreaks working closely with local and international health authorities and NIAID. With key sites in Asia and the Americas, we will use innovative molecular and serological methods to identify emerging pathogens and to address fundamental questions in dengue and other arboviral epidemiology and test viral, host and environmental determinants of differences between sites along a gradient of urbanicity. Our overarching goal is to develop an interconnected, harmonized network of clinical and laboratory sites to strengthen research programs, compare disease epidemiology and severity in different regions, develop and implement cutting-edge diagnostic methods, and respond efficiently and effectively to outbreaks. Standardized hospital studies and community-based cohorts in Ecuador, Nicaragua and Sri Lanka will characterize and compare human arboviral illnesses across urban, peri-urban and rural sites and develop sustainable infrastructure to rapidly respond to epidemics together with Ministries of Health, comple- mented by outbreak investigation, surveillance of non-human primates, and vector incrimination. We will imple- ment standardized plans for study administration, data and clinical management, and statistical analysis across sites, supported by an extensive on-site training program. Aim 1 will establish standard and novel multiplex assays at each site for surveillance, diagnosis and research of arboviruses and other pathogens. Aim 2 com- pares dengue/arbovirus epidemiology and transmission in cohort studies located in ecologically distinct regions over a continuum of urbanicity. In Aim 3, we will characterize complete viral genome sequences for comparative studies of arboviral phylogenetics, phylogeography and molecular epidemiology. Aim 4 consists of surveillance, identification, and characterization of novel and unrecognized human pathogens from severe hospitalized cases, unexpected outbreaks, vectors and non-human primates. Molecular and serological assays will be developed for newly identified pathogens and quickly implemented across study sites to characterize the epidemiology and clinical manifestations and will be made available to the EIDRC network. In sum, our A2CARES Consortium will provide valuable new tools and knowledge and 3 interconnected centers in Latin America and South Asia that will be able to respond to outbreaks and to study emerging and endemic infectious diseases far into the future.",,2025,UNIVERSITY OF CALIFORNIA BERKELEY,1546211,Viruses,Not applicable,Not Applicable,Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease transmission dynamics | Disease surveillance & mapping",2020 +P22146,5R01AI165560-03,Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats,"Project Summary Each year, approximately 400 million people are infected with an arboviral disease from the bite of an Aedes spp mosquito. Aedes spp. mosquitoes are a leading public health threat due to their high competency to vector multiple pathogens, their preference to bite humans, and their ability to adapt to new domestic environments. In the US, reintroduction and establishment of Aedes aegypti and Aedes albopictus mosquito populations has resulted in local epidemics of Zika, dengue and chikungunya in the past decade. Unfortunately, mosquito control programs in the US generally operate with limited budgets, forcing the majority of insecticide spraying to be conducted in reaction to population exposure instead of targeted prevention, which has also contributed to considerable growth of insecticide resistant populations, yielding a widening gap of infrastructure vulnerability. Our current proposal aims to leverage existing technologies from non-health disciplines to advance mosquito detection and abatement. We propose to validate the use of technology-driven mosquito traps that allow for high- throughput identification and counting of Aedes mosquitos at various life stages to inform decision making when selecting areas for insecticide spraying and abatement. Additionally, we propose to develop rigorous remote sensing workflows for identification of neighborhood-level Aedes abundance risk and rapid detection of individual Aedes mosquito breeding habitats on a household-level. This innovative proposal uses multi-year and real-world mosquito data from two different metropolitan areas to statistically adjust for variances in geographic ecologies, urban microclimates, seasonal climate patterns, and annual weather events. Our study will result in low-cost tools immediately ready for broad distribution and integration by vector control agencies nationally. The outcomes of our study have promise to directly impact vector control agency’s decision-making processes for mosquito trapping site selection, inform preventative abetment protocols, and shorten the time required for mosquito collection and identification. Further, integration of our proposed technology traps and informed site selection maps will increase overall collection volumes while preserving scarce resources for local vector control agencies. This proposal has the potential to create a paradigm shift in how we approach vector control globally, with a targeted intervention resulting in significant economic, environmental, and clinical benefits.",,2026,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,740913,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P22150,5R21AI171913-02,Human sweat taste and contact-guided behavior in Aedes aegypti,"PROJECT SUMMARY Mosquitoes are responsible for transmitting disease to hundreds of millions of people each year. Behavior- modification strategies have been major tools in surveillance and control efforts. A lot of attention has been devoted to elucidating and manipulating detection of thermosensory and olfactory cues that drive host-seeking behavior. However, a critical gap exists in our understanding of contact chemosensation in mosquito-host interactions, despite the fact that biting and blood feeding behaviors are crucial factors in driving disease transmission. After a mosquito has found a host, she lands on and examines the skin surface, and probes it with her stylets before initiating a blood meal. It is well known that the human skin surface is replete with chemicals, including those found in sweat. An understanding of whether human sweat cues can be sensed by the mosquito taste system, and if so, whether these cues activate behaviors that precede initiation of blood meals, would provide a valuable entry point for developing new behavior-modifying tools for surveillance and control. Our model of choice is Ae. aegypti, a vector of Dengue, Chikungunya, and Zika viruses, which is responsible for an enormous worldwide burden on human health, and is now also established in some regions of the United States. We propose to explore the hypothesis that soluble compounds present on human skin are sensed by the mosquito taste system and activate close-range behaviors that precede blood feeding. We focus on human sweat components, which include free amino acids in addition to salts, acids and ammonia derivatives. The premise behind our hypothesis is supported by our pilot data, in which we find that an artificial sweat mixture as well as certain individual amino acids and salt can activate taste neurons in female mosquitoes. Further, mixtures presented on a filter paper target can stimulate interaction and probing attempts in mated females. The specific goals of our proposal will be accomplished via two aims. In AIM 1, we will create a map of taste responsivity of human sweat components and mixtures in the female Aedes aegypti mosquito. We will determine if these stimuli promote residency or pre-feeding behaviors such as labellating and probing using independent population-based and single-female behavior assays. In AIM 2, we will evaluate whether cellular and behavioral responses to human sweat tastants are altered by knocking out selected taste receptors/co- receptors using CRISPR/Cas9-mediated genome editing. The results of the proposed studies will provide important molecular and neurophysiological insights into mosquito taste-guided behaviors elicited by compounds found in human sweat.",,2024,UNIVERSITY OF CALIFORNIA RIVERSIDE,194375,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22151,1R01AI179056-01,Sex determination and the sex-determining locus in aedine mosquitoes,"Abstract Sex is critical to the survival and evolution of sexually reproducing organisms including mosquitoes. A dominant male-determining factor (M factor) is the primary signal that controls sex-determination in mosquitoes. Nix, the M factor in the yellow fever mosquito Aedes aegypti, is the first M factor found in mosquitoes. In a simplified model, the expression of Nix, a predicted RNA-binding protein, leads to male- specific splicing of the pre-mRNAs of two conserved transcription factors, doublesex (dsx) and fruitless (fru), which program male sexual differentiation. In Aedes the M factor is located within the male- determining locus (M locus) on one of the “autosomes”. This pair of “autosomes” are so-called homomorphic sex chromosomes that are cytologically indistinguishable except in the region around the sex locus. The Ae. aegypti M locus is a ~1.3 Mbp repeat-rich region that contains Nix and four other protein-coding and 25 long non-coding RNA genes. The Nix transgene alone, in the absence of the M locus, is sufficient to convert females into fertile albeit flightless males, and myo-sex, a myosin heavy chain gene also in the M-locus, is required for male flight. The M- and m-bearing chromosomes in Aedes mosquitoes provide an opportunity to gain insights into the evolution of homomorphic sex chromosomes. In addition to its basic biological importance, Ae. aegypti is a major vector for the dengue, chikungunya, and Zika viruses. No specific treatment for dengue exists and the first dengue vaccine is recommended only for a limited population. Prevention of these vector-borne infectious diseases relies heavily on effective vector control. However, increasing insecticide-resistance poses a significant threat. Therefore, novel control strategies are urgently needed. Only female mosquitoes feed on blood and transmit pathogens, and for the most part females determine the size and distribution of the mosquito population. We are interested in deciphering the mechanism of sex-determination, investigating sex chromosome evolution, and translating such fundamental knowledge into safe, efficient, and diverse methods to control diseases that are transmitted by Ae. aegypti. Building on recent progress, we will pursue the following specific aims: 1) Decipher the sex locus in Ae. aegypti, 2) Identify and characterize the target(s) of Nix, and 3) Develop efficient sex-separation methods through Nix-mediated innovations.",,2028,VIRGINIA POLYTECHNIC INST AND ST UNIV,774520,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2023 +P22152,5R03AI167042-02,Phenotypic characterization of T’Ho virus and the development of tools for its serologic diagnosis,"PROJECT SUMMARY T’Ho virus is a poorly characterized flavivirus recently discovered in Culex quinquefasciatus mosquitoes in the Yucatan Peninsula of Mexico. The genome of T’Ho virus was fully sequenced but an isolate was not recovered by suckling mouse brain inoculation or by virus isolation in vertebrate or mosquito cell cultures. Genome sequence alignments revealed that the closest known relatives of T’Ho virus are mosquito-transmitted flaviviruses associated with life-threatening human disease. Rocio virus, a BSL-3 pathogen, is the closest known relative, followed by Ilhéus, St. Louis encephalitis, Japanese encephalitis and West Nile viruses. Because T’Ho virus is most closely related to known human pathogens, it too could be a cause of human disease. Clinical and serological studies need to be performed to investigate this issue. There is also an important need to perform in vivo experimental infections to identify competent vertebrate host and vector species. The ability to perform these experiments is severely restricted by the unavailability of an isolate. To address this issue, recombinant technology will be used to create infectious viruses that can be used for T’Ho virus research and diagnosis. The first objective is to generate recombinant T’Ho virus and characterize its in vitro host range and replication kinetics. Based on its close phylogenetic relationship with flaviviruses that cycle between mosquitoes and vertebrate hosts, it is hypothesized that T’Ho virus replicates in both mosquito and vertebrate cells. The second objective is to create a chimeric virus that can be used in BSL-2 laboratories for the detection of neutralizing antibodies to T’Ho virus. Because T’Ho virus is closely related to several BSL-3 pathogens, it could eventually be classified as a BSL-3 agent. However, many arbovirus laboratories, particularly those in Latin America, lack BSL-3 facilities. Therefore, a chimeric virus will be generated by substituting the major structural protein genes of Zika virus, a BSL-2 pathogen, with the corresponding region of T’Ho virus, producing a virus that can be used in BSL-2 laboratories. It is hypothesized that the aforementioned genetic exchange is functionally compatible and will generate a chimeric virus that forms plaques in vertebrate cell monolayers. The proposed studies provide the foundation for many future experiments. Vertebrate animals and mosquitoes can be experimentally inoculated with the recombinant virus to identify competent reservoir hosts and vectors of T’Ho virus, providing insight into its transmission cycle. The recombinant virus will allow researchers to monitor humans and vertebrate animals in Mexico and elsewhere in the Americas for antibodies to T’Ho virus by plaque reduction neutralization test (PRNT). The PRNT is the gold- standard serologic technique for the diagnosis of flavivirus infections and it requires live virus. The chimeric virus can be used when BSL-3 facilities are unavailable. Flaviviruses are known for their serologic cross-reactivity; thus, it is likely that antibodies to T’Ho virus can bind to and neutralize other flaviviruses. This raises the possibility that some human and vertebrate animals previously tested by PRNT in serologic investigations in Latin America contained antibodies to T’Ho virus but were misdiagnosed. It is important that infectious T’Ho virus is available so it can be included in PRNTs and considered in the differential diagnosis.",,2025,IOWA STATE UNIVERSITY,76500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22154,5R01AI150672-03,Dengue virus mRNA lipid nanoparticle vaccine,"Nearly 400 million people are infected with dengue virus (DENV) each year through the bite of infected mosquitos concentrated in the tropical and subtropical regions of the world. Symptoms can range from febrile illness to severe dengue that manifests as plasma leakage, sudden loss of blood pressure, organ failure, and shock that can ultimately lead to death. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross- reactive, poorly-neutralizing epitopes lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). Additionally, DENV immunity has been implicated in increased susceptibility to Zika virus through ADE. Currently there are no available therapeutics to combat DENV disease. Dengvaxia, the only licensed DENV vaccine, was found to increase hospitalization rates in naïve populations, and thus is not recommended for a large portion of at-risk individuals. There is an urgent need for a safe and efficacious vaccine that elicits a robust, balanced, neutralizing response to all four DENV serotypes. We propose to develop a novel DENV vaccine utilizing an emergent platform: mRNA encoding for viral proteins encapsidated in a lipid nanoparticle (LNP). mRNA-LNP vaccines elicit robust humoral and cell-mediated immune responses in a safe, non-infectious platform. Additionally, we can direct the host immune response towards neutralizing epitopes by mutating the mRNA encoding for the viral protein. We hypothesize that a sequence-engineered tetravalent mRNA-LNP vaccine will induce a balanced, protective immune response against all four serotypes of dengue without the potential of causing immune enhancement and ADE. In Aim 1 of this study we will generate and optimize mRNA constructs encoding for the pre-membrane and envelope viral glycoproteins for all four serotypes of DENV. We will mutate the poorly-neutralizing, cross-reactive epitopes that drive ADE. In Aim 2 we will characterize the immune response to the vaccines in a mouse model. In addition to quantifying humoral and cellular immune responses, we will also measure the immune enhancement capacity of all vaccines. In Aim 3, we will evaluate vaccine efficacy and safety in susceptible mouse models, by challenging vaccinated mice with different DENV serotypes to monitor protection and ADE. We will also determine mechanism of protection via adoptive transfer experiments. Through this study, we will identify DENV vaccines that demonstrate broad protection and lack of immune enhancement for further evaluation as candidate human vaccines.",,2025,UNIVERSITY OF ILLINOIS AT CHICAGO,614090,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +P22156,5R01AI153064-04,Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses,"ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no effective vaccines are available. Protective immunity against many pathogens can be achieved through long- lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly, our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.) Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced immune mechanisms that regulate the biology of Tfh cells. This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and durable neutralizing antibody responses. This finding could have a significant impact on vaccine development as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable protective antibody responses against many pathogens. We believe that the data generated in this proposal will be capable of moving this vaccine adjuvant towards clinical trials.",,2024,UNIVERSITY OF PENNSYLVANIA,708799,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22157,5R01AI155959-03,"Sample-to-Answer, Rapid, Multiplexed and PCR-Free Diagnostics of Arboviral Diseases in Resource Limited Settings","Arthropod-borne viruses (arboviruses) comprise many of the most important ‘emerging pathogens’ due to their geographic spread and their increasing impact on vulnerable human populations. There is urgent need for easy-to- operate and rapidly deployable diagnostic tools that can handle blood samples in a closed sample-to-answer manner. Here, we propose to develop a novel diagnostic technology that can detect viral antigens in an inexpensive, ultrasensitive, specific, and multiplexed manner. We will develop our novel approach into standalone tool with a detection capability at attomolar sensitivities (comparable to nucleic acid amplification tests) to diagnose arboviral infections with minimal user interference. The integrated diagnostic platform will utilize a novel surrogate approach, microfluidic integration, and a multiplexed detection scheme with the capacity to distinguish arboviral infections. The system will be designed to initiate diagnosis from serum/plasma/blood and provide a sample-to-answer diagnostic within less than 35 minutes using less than 100 Ã'µL blood samples at a cost of $2 per test. Collaborative work proposed for this NIH/NIAID R01 Grant involves integration of nanophotonic engineering (Yanik Group), molecular virology (Pinsky Group), and infectious diseases epidemiology (LaBeaud Group) to build and field-test our novel point-of-care viral diagnostic platform with Windward Islands Research and Education Foundation (WINDREF) and St. George’s University teams (Macpherson, Waechter and Noel Groups). Preliminary validation tests with patient samples will be initially performed at Stanford Medical Facility in collaboration with LaBeaud and Pinsky groups. Subsequently, three prototypes will be transferred to Grenada for field-testing initially at central laboratories then to resource-poor settings in small towns. Yanik group will provide the necessary expertise for integration of molecular and nanoengineering components and demonstration of a practical prototype as well as evaluating the application of prototype(s) developed under this proposal with patient samples (LaBeaud and Pinsky Groups). System will be iteratively optimized and a rugged platform suitable for field settings will be developed.",,2025,UNIVERSITY OF CALIFORNIA SANTA CRUZ,749984,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P22158,5R01AI148144-04,Clearance of Blood-Borne Arboviruses,"PROJECT SUMMARY Arboviruses cause serious human disease. Viremia level following arbovirus infection of vertebrates is a critical determinant of viral transmission cycles, global viral spread, and disease severity in individuals. Surprisingly, the factors that dictate viremia following arbovirus infection are poorly defined. We found that multiple arboviruses, including chikungunya (CHIKV), Ross River (RRV), o’nyong nyong (ONNV) and Zika viruses, are cleared from the circulation by phagocytic cells. Experiments in splenectomized mice showed that the spleen is dispensable for arboviral clearance. Instead, virus accumulates in the liver and clearance is independent of natural antibodies and complement factors, suggesting a non-opsonic mechanism. Consistent with this idea, clearance of circulating alphaviruses was blocked by competitive inhibitors of scavenger receptors (SRs) that mediate non- opsonic uptake of non-self and modified-self ligands. Remarkably, we found that single lysine (K) to arginine (R) mutations in the E2 glycoproteins of CHIKV and ONNV (E2 K200R), as well as RRV (E2 K251R), abrogated clearance of circulating alphavirus particles by phagocytic cells, and promoted rapid viral dissemination to distal tissues. Moreover, substitution of CHIKV E2 K200 with a variety of other amino acids also allows for clearance evasion, suggesting a specific interaction between key K residues and a host factor. Ks are targets for post- translational modification (PTM), and mass spectrometry analysis of E2 in virions revealed that CHIKV E2 K200 is ubiquitinated. These experiments have revealed a previously unrecognized pathway that controls arbovirus viremia and dissemination in vertebrates. We hypothesize that PTM of key Ks in viral glycoproteins licenses the capture of circulating arboviruses via SRs expressed on liver Kupffer cells (KCs). In Specific Aim 1, the cell types that capture circulating arboviruses will be defined. We also will determine the role of KCs in viral clearance and dissemination, and the development of anti-viral immunity. Finally, we will evaluate the role of phagocytic cells, and KCs specifically, in the clearance of a genera-spanning panel of arboviruses. In Specific Aim 2, we will define the spectrum of blood-borne arboviruses susceptible to SR-mediated clearance. We will use ELISA and cellular binding assays to determine the murine and human SR(s) that bind virus particles. Using SR knockout mice, we will determine the role of specific SRs in clearance of circulating arboviruses. In Specific Aim 3, we will define the role of E2 ubiquitination in the clearance of circulating CHIKV and RRV. We will use mass spectrometry-based proteomics to determine K residues in arboviral particles that are modified with ubiquitin or other PTMs. Finally, we will use a collection of reverse genetics systems to define the role of specific modified Ks in arboviral clearance from the circulation. This work will provide new mechanistic understanding of arbovirus clearance from the circulation. Elucidating these mechanisms could provide new insight into viral transmission, dissemination, and pathogenesis, identify new risk factors of severe disease, and reveal new therapeutic targets for the treatment of arboviral disease.",,2025,UNIVERSITY OF COLORADO DENVER,120475,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22160,5R01AI151029-04,Next Generation Resolution of Antiviral Gene Networks,"SUMMARY As the primary mediators of the innate response to viral infection, type I interferons (IFN-I) establish an antiviral state in both infected and uninfected bystander cells through the induction of several hundreds of interferon stimulated genes (ISGs). The mechanisms by which the coordinated activities of these ISGs confer resistance to diverse viruses, and the regulatory circuits that modulate their expression remain poorly understood. Working with unique samples from individuals with hereditary syndromes of dysregulated IFN-I responsiveness, we have identified a collection of thirty ISGs that confer resistance to diverse viruses (increased protection against RNA and DNA viruses with both high and low pathogenic burden). We have also uncovered previously unappreciated negative feedback mechanisms of IFN-I signaling. We have found that these regulatory circuits, as well as ISG expression patterns, vary significantly across different cell types at steady state and upon IFN-I stimulation. Recent technological advances now enable us to explore these cooperative ISG antiviral functions and negative feedback mechanisms at unprecedented depth and resolution. In the studies proposed here, we will identify subsets of ISGs sufficient to confer broad protection against multiple viruses using a novel single cell RNA-Seq strategy. This approach provides the throughput required to conduct complex combinatorial experiments while maintaining the high resolution to test specific hypotheses. Results may offer new broad spectrum antiviral therapeutic strategies, which would be of particular value against emerging viral pathogens. We will also investigate in detail the mechanisms by which IFN-I signaling establishes a lasting imprint on cellular responsiveness to subsequent IFN-I stimulation. This recently described but incompletely characterized phenomenon likely has important implications for successive infectious challenges and viral susceptibilities. Combining a unique collection of clinical samples, cutting edge technologies, and diverse and complementary expertise in immunovirology from our two laboratories, these studies are expected to address long standing, fundamental questions in innate antiviral immunity, as well as to pioneer new directions for developing antiviral therapies.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,662018,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +P22161,1DP2AI171150-01,Maternal immune activation remodeling of offspring glycosaminoglycan sulfation patterns during neurodevelopment,"ABSTRACT Maternal immune activation (MIA) during prenatal or postnatal development significantly increases the risk for offspring neurodevelopmental disorders (NDDs) later in life. Growing evidence suggest that regardless of the MIA stimuli (infectious or environmental), offspring exhibit an enhanced risk for lifelong neuropathology defects ranging from reduced brain volume to alterations in neurocircuit organization. The brain extracellular matrix- containing chondroitin and dermatan sulfate-glycosaminoglycans (CS/DS-GAGs) are key regulators of brain development and can be biochemically altered by neuroimmune responses. Defects in CS/DS-GAG abundance and/or sulfation patterning (4S (CS-A), 2S4S (CS-B/DS), 6S (CS-C), 2S6S (CS-D), 4S6S (CS-E), 0S (CS-O)) result in the manifestation of similar neuropsychiatric behaviors as reported in offspring affected by MIA, but whether and how MIA affects offspring brain matrix is unknown. By employing a novel laser capture microdissection coupled mass spectrometry methodology (LMD-LC-MS/MS), our Preliminary Data provide the first evidence for inter- and intra-regional differences in CS/DS-GAG sulfation pattern differences throughout the developing mouse and non-human primate (NHP) brain. Specifically, the hippocampus exhibits a significant increase in both developmental 6S (CS-C) and 2S6S (CS-D) isomers compared to the cortex, implying that the hippocampus remains developmentally plastic long after the maturation of adjacent regions. Moreover, we show that infectious Zika virus MIA during gestation in NHPs decreases the abundance of the developmental 2S6S (CS-D) axonal growth factor attractant isomer in the hippocampus, suggesting stunted neurocircuit formation after infectious MIA, while the non-infectious maternal high fat diet (mHFD) MIA during lactation in mice decreases the abundance of the developmental 6S (CS-C) plasticity isomer in the hippocampus, suggested accelerated early maturation of hippocampal neurocircuits in response to non-infectious MIA. The implication that both infectious and non-infectious MIA insults influence the spatiotemporal regulation of brain CS/DS-GAG sulfation patterns fits a global interconnecting theory linking a range of MIA insults with changes in offspring brain neurodevelopment through re-coding of CS/DS-GAGs. From these results, we propose to 1) determine how MIA exposure affects spatiotemporal expression of offspring CS/DS-GAGs and link these changes to NDDs later in life, 2) mechanistically investigate how these MIA-induced changes in offspring CS/DS-GAGs influence glycan- protein interactions involved in neurodevelopment, and 3) engineer a state-of-the-art nanopore sequencing technology capable of single-molecule sequencing of biological CS/DS-GAGs to discover glycan-protein binding elements. This multidisciplinary proposal has important translational potential to clarify how MIA exposure leads to neuropsychiatric illness through changes in CS/DS-GAG sulfation patterning during childhood neurodevelopment and provides valuable targets in the prevention and treatment of mental health diseases.",,2028,UNIVERSITY OF WASHINGTON,520181,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2023 +P22164,5S06GM146125-02,UA Project: Advancing Vector-borne Disease Surveillance in American Indian Communities,"Project Summary/Abstract The Inter Tribal Council of Arizona, Cocopah Environmental Protection Office staff, medical entomologists from the University of California, vector-borne disease researchers from the University of Arizona and other community partners will build upon existing participatory research and outreach partnerships in the proposed project. Arizona often ranks amongst the highest in West Nile virus infection and related deaths relative to other states. Additionally, high populations of the invasive yellow fever mosquito Aedes aegypti in communities along southern border areas makes mosquito and pathogen surveillance critically important. Ae. aegypti is the primary vector of dengue and Zika viruses which circulate in the neighboring border states of Sonora and Baja California, Mexico. Ticks are important vectors causing human disease. Among the most significant is Rocky Mountain spotted fever (RMSF), a bacterial infection caused by Rickettsia rickettsii, which kills more people in North America than any other tickborne disease. Native American populations are disproportionately impacted. Since the first locally acquired case was identified in Arizona in 2003, the disease has become endemic in many Native American communities. In Arizona, R. rickettsii is vectored by the brown dog tick Rhipicephalus sanguineus and to date there have been more than 436 cases of RMSF with a case fatality rate of 10%, which is 15 times the national rate for this disease. There have been no surveillance efforts for vector or pathogen prevalence outside of post-epidemic events. Supportive efforts are needed to identify high-risk surveillance gaps, undertake vector and pathogen prevalence assessments, and generate access to essential infrastructure and services in the short-term. Vector-borne Disease Research Committees (VbDRC) within collaborating tribal communities will direct high priority vector surveillance and inform Tribal leadership of technical findings. Creation of Vector Risk Mitigation Plans and relevant community specific practicum training will be provided for tribal environmental health, public health and medical practitioners serving communities. Additionally, investment in Native American students through financially supported vector research experiences will help build the future public and environmental health workforce. There is strong evidence that student research experiences improve educational persistence, thus UA faculty and VbDRC members will mentor Native American students through community-based research projects.",,2026,"INTER TRIBAL COUNCIL OF ARIZONA, INC.",101652,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease surveillance & mapping,2022 +P22165,5R01AI153044-03,Statistical innovation to integrate sequences and phenotypes for scalable phylodynamic inference,"PROJECT SUMMARY/ABSTRACT This proposal targets the design, development and distribution of Bayesian statistical methods and software to study the historical and real-time emergence of rapidly evolving pathogens, such as Ebola, human immun- odeficiency, inï¬Â'uenza, Lassa, SARS-CoV-2, West Nile, yellow fever and Zika viruses. The proposal exploits novel scalable data integration to equip us for large-scale epidemics and pandemics and help inform action- able public health policy. Our multidisciplinary team carries expertise across statistical thinking, data science, evolutionary biology and infectious diseases to leverage advancing sequencing technology and high-throughput biological experimentation that can characterize 1000s of pathogen genomes, phenotype measurements, eco- logical and clinical information from a single outbreak. Our chief innovations are three-fold. First, we will invent and implement scalable Bayesian phylodynamic techniques to integrate phenotypic measurements and study their correlated evolution with disease spread. Second, we will foster biologically-rich evolutionary models to map and understand heterogeneity in disease evolution through new efficient algorithms. Third, we will develop high-dimensional and mixed-type phenotype models to link concerted viral genotype / phenotype changes using massively parallel computing. Although no competing software exists to integrate phenotype and sequence data at this scale, we will compare restricted cases of our models with reduced datasets to current state-of-the-art approaches to evaluate computational performance improvement and bias that these limitations inject using real- world examples. This proposal will deliver low-level toolbox libraries and user-friendly software for deployment across a rapidly expanding range of large-scale problems in statistics and medicine.",,2025,UNIVERSITY OF CALIFORNIA LOS ANGELES,459019,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P22167,5R01AI146152-05,Validating the Flavivirus Envelope Protein as an Antiviral Target,"PROJECT SUMMARY Dengue virus (DENV) and other flaviviruses are major human pathogens that cause significant disease. Transmitted by widespread mosquito species, many of these viruses spread rapidly and can have a devastating impact on public health where prior immunity does not exist. There is thus a significant need for countermeasures to combat both current and future flavivirus threats. Major limitations in current antivirals development are the relatively small number of validated antiviral targets, most of which are viral enzymes (e.g., polymerases, proteases); the low barrier to resistance when direct-acting antivirals are used as monotherapies; and the narrow spectrum activity of most of these agents (“one bug, one drug”). New classes of targets that can mediate broad-spectrum activity against related viruses and that have high barriers to resistance are particularly needed to combat emerging viruses since we generally lack sufficient time and resources to develop new drugs on a useful time scale once these viruses pose significant threats. Small molecules targeting the flavivirus envelope protein, E, have the potential to mimic the humoral immune response by engaging their target extracellularly and blocking viral entry early in the replication cycle. We have identified multiple small molecule inhibitor series that bind to the DENV envelope protein, E, and inhibit E-mediated membrane fusion during viral entry even when only a minority of copies of E on the particle are inhibitor-bound. These compounds bind in a pocket between domains I and II and inhibit West Nile, Zika, and Japanese encephalitis viruses due to at least partial conservation of this site. We recently established a target-based assay and validated its use in the identification of new inhibitors of DENV and Zika E proteins that bind in the conserved pocket and that have more drug-like properties than our original inhibitors. Building on this work, we now propose a comprehensive plan to rationally optimize small molecule inhibitors of the DENV E protein as a potential anti-viral strategy. Towards this end, we will combine modeling and structure- guided drug design with an efficient screening cascade using complementary target-based biochemical, cellular and mechanistic assays to enable efficient optimization of two chemically distinct lead series. Our primary goal in this work is to demonstrate antiviral efficacy in a murine model of DENV infection, thus laying the foundation for first-in-class direct acting antivirals to treat the growing global threat that DENV poses.",,2025,STANFORD UNIVERSITY,961202,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22168,3D43TW010923-05S1,Nicaraguan Emerging and Endemic Diseases (NEED) Training Program,"ABSTRACT The growing, global impact of emerging and endemic viral diseases is a critical public health issue. The explosive spread of Zika virus throughout Latin America and the Caribbean in 2015 followed only two years after a similar pattern of spread of chikungunya virus. In 2017, yellow fever virus from Amazon regions emerged in Rio de Janeiro, underscoring the risk of a major urban outbreak, and in 2020 the entire world were affected by the SARS-CoV-2 pandemic. In addition to these emerging and reemerging viruses, endemic viruses continue to cause a high burden of disease. Caliciviruses are now the leading causes of childhood diarrhea in Nicaragua, influenza and respiratory syncytial virus continue to cause a high burden of respiratory disease, and all four dengue serotypes are now endemic. We have designed a program to train a cadre of innovative Nicaraguan scientists to confront these emerging and endemic pathogens of high priority. The rationale for this program is to protect the public health of populations by increasing the numbers and expertise of local scientists to 1) describe the epidemiology of these viral pathogens, 2) understand their impact on morbidity and mortality, and 3) identify evidence-based approaches to reduce their prevalence and burden of disease. Our program’s original objectives included: 1) Provide long-term, pre-doctoral training in infectious disease epidemiology at UNC to two young investigators from UNAN-León. These graduates will contribute to infectious disease research in the region to address pressing local research agendas; 2) Create a sustainable supply of well-trained biomedical scientists in the region by establishing an accredited PhD program in Biomedical Sciences at UNAN-León; we will enroll five pre-doctoral candidates in the initial cohort. This program built upon a successful Master’s program of Microbiology in place at UNAN-León and fills a huge need in the region for PhD- trained infectious disease investigators. 3) Foster professional growth and research skills development among 140 trainees of all levels, including local faculty, to ensure academic and research success. Robust short-term trainings in professional and research skills needed to become an independent investigator and successful academician were provided to both trainees and local faculty to ensure that the program’s impacts extend more broadly. Unfortunate political events in Nicaragua during the final year of our award have forced us to adapt our second objective, as we are no longer able to partner with UNAN-León. Our 3 Biomedical Sciences PhD students need to complete their PhD training outside the country. The goal of this Administrative Supplement is to fund their training with experienced microbiology faculty at the University of Costa Rica, one of the only universities in the region to provide PhD training. We also request an additional year of funding for a trainee whose PhD training was delayed due to severe COVID. This will ensure that the investment made in these individuals translates into the completion of their PhD training and the increase in infectious disease research capacity in Central America.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,136400,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Policy research and interventions,2023 +P22170,1R21EB034970-01,Engineering a human neuroimmune specific viral vector from Zika virus,"PROJECT SUMMARY Inflammation has been implicated in nearly every neuropsychiatric and degenerative disease, yet neuroimmune cells remain nearly intractable by every available therapeutic strategy. Small molecule drugs consistently fail clinical trials, as neuroimmune signaling pathways have essential pleiotropic functions in neighboring cell types. Meanwhile cell type selective therapies remain elusive, as microglia, and other neuroimmune cells, are intrinsically resistant to gene therapy vectors. Overcoming these unique challenges demands a new approach to medicine, drawing from an unlikely source of neuroimmune specific bioactivity. In nature, the Zika virus (ZKV) infects microglia, suppresses inflammation, and stimulates autophagy so expertly that almost half of infections go unnoticed. If this bioactivity could be safely refined, it would offer relief for neurodegenerative disorders from Parkinson’s to Alzheimer's disease. Parsing therapeutic from pathogenic mechanisms of the ZKV genome presents much greater complexity than ever previously addressed, but recent advances make it possible. Recombinant ZKV vectors, already in use, provide starting material for synthetic biology, while new viral assisted and continuous evolution methods allow bioengineering at scales capable of reshaping whole genomes. We can harness ZKV’s microglia specific immunosuppressive mechanisms into therapies with potential beyond any current technology. This proposal presents the first steps along the path towards an entirely new kind of therapy for neurodegenerative disorders.",,2026,ARIZONA STATE UNIVERSITY-TEMPE CAMPUS,184461,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",,2023 +P22174,3R01AI169443-01S1,"Autonomously deploying, co-evolving SARS-CoV-2 antiviral: a new paradigm for pandemic prevention","PROJECT SUMMARY SARS-CoV-2, like all viruses, mutates and transmits; current medical countermeasures do not. This fundamental mismatch between dynamic viruses and our state-of-the-art static interventions means that vaccines and antiviral therapies often require frequent re-design and re-development, necessitating repeated (sometimes annual) resolutions to manufacturing and deployment challenges. Without fundamentally different forms of intervention to overcome this mismatch, future pandemics could rival or eclipse the catastrophic loss-of-life and economic impacts of SARS-CoV-2. To surmount the barriers thwarting current interventions, this proposal will engineer therapeutic molecular parasites of SARS-CoV-2 that can co-adapt and transmit among infected hosts. The key innovations of this approach are that these therapeutic parasites: (i) establish co-evolutionary arms races, co- evolving with wild-type virus to overcome resistance, (ii) replicate and self-renew, acting as single-administration therapies that circumvent compliance issues, and (iii) spread via the exact same risk factors and transmission routes as SARS-CoV-2â€Â""autonomously utilizing superspreaders to deploy the interventionâ€Â""thereby circumventing manufacturing-at-scale and roll-out challenges. By design, these ‘piggybacking’ molecular parasites cannot replicate in uninfected hosts. Epidemiological models indicate that such molecular-parasite therapies would surmount the universal barriers to pandemic control and lower prevalence for many viruses below levels achievable by vaccination or antiviral therapy campaigns. The molecular rationale for developing molecular-parasite antivirals rests on ablating essential protein-encoding elements (i.e., trans-acting factors) to create conditionally replicating vectors that produce Therapeutic Interfering Particles (TIPs) when complemented in trans by wild-type virus superinfection. The crucial difference between TIPs and classical defective viral particles is that TIPs are engineered to have an R0 > 1â€Â""they efficiently mobilize, and transmit. As deletion variants, TIPs act as parasites, replicating only in virus-infected cells by stealing critical replication and packaging elements from the wild-type virus. By starving the wild-type pathogen of these critical elements, TIPs reduce wild-type pathogen levels. Critical feasibility precedents include that TIPs have been engineered to inhibit other viruses in vivo. Regulatory and ethical precedents include initial FDA clearances for HIV TIP Phase-I clinical trials supported by the NIH and DoD. This proposal will screen randomized synthetic libraries of SARS-CoV-2 variants to identify TIP candidates, test TIP efficacy and transmissibility in animal models, devise and test delivery and dosage formulations, and test tolerability, safety, and immunogenicity in a Phase-I clinical trial. The deliverable of this project will be the creation of a novel paradigm to counter SARS-CoV-2 and emerging pandemics by development and de-risking of an intervention that overcomes the universal barriers to infectious disease control.",,2024,"VXBIOSCIENCES, INC.",1997089,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22177,3R01AI154274-02S1,Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach,"The current COVID-19 crisis starkly illustrates the need to develop new modalities for the therapeutic treatment of pathogenic single-stranded RNA (ssRNA) viruses, including against novel viruses that have yet to emerge. Human oxysterol-binding protein (OSBP) has recently been determined to be a critical mediator in the replication of a broad spectrum of ssRNA viral human pathogens, including the enteroviruses, rhinovirus, hepatitis C, Zika virus, Dengue fever viruses, and coronaviruses. OSBP is an ER-located, non-enzymatic protein reported to function as an important lipid sensor and lipid transporter in eukaryotic cells. Published research, including our own recent publications, has established the antiviral activity of structurally-diverse OSBP- targeting small molecules against multiple RNA pathogenic viruses. These discoveries present the opportunity for a paradigm shift in antiviral drug development: potentially drug targeting a human host protein, OSBP, that is required for viral proliferation of a broad-spectrum of RNA viruses, as opposed to targeting viral proteins present in individual viruses. We have discovered that transient, low dose treatment with the OSBP-targeting compound OSW-1-compound induces a longterm, multigenerational repression of OSBP, and the cells with repressed OSBP show a pronounced inhibition of ssRNA viral replication. Our preliminary results show that the OSW-1- compound has prophylactic antiviral activity at low nanomolar concentrations against several ssRNA viruses, including against one coronavirus tested. The longterm repression of OSBP, triggered by OSW-1, has no effect on cellular division, viability, or morphology. The purpose of this proposal is to understand the cellular role of OSBP in innate antiviral response. Our preliminary results show that OSBP: 1) regulates mTORC1 activity, 2) induces autophagy; 3) slows global protein translation; and 4) activates alternative splicing nonsense- mediated decay (AS-NMD) process, which is an RNA regulatory process. All of these OSBP- involved cellular processes would limit ssRNA viral replication individually, but there is little insight into the organization of these systems to establish a coordinated antiviral response.Our overall hypothesis is that OSBP serves in a major regulatory role to coordinate a multifaceted innate antiviral response to ssRNA infection. We propose a complete model of how OSBP senses early- stage viral infection and then triggers a multisystem response to block viral replication in cells, including through modulating mTOR1C activity and the AS-NMD system.",,2026,UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR,34831,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22178,5R01AI154274-03,Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach,"The current COVID-19 crisis starkly illustrates the need to develop new modalities for the therapeutic treatment of pathogenic single-stranded RNA (ssRNA) viruses, including against novel viruses that have yet to emerge. Human oxysterol-binding protein (OSBP) has recently been determined to be a critical mediator in the replication of a broad spectrum of ssRNA viral human pathogens, including the enteroviruses, rhinovirus, hepatitis C, Zika virus, Dengue fever viruses, and coronaviruses. OSBP is an ER-located, non-enzymatic protein reported to function as an important lipid sensor and lipid transporter in eukaryotic cells. Published research, including our own recent publications, has established the antiviral activity of structurally-diverse OSBP- targeting small molecules against multiple RNA pathogenic viruses. These discoveries present the opportunity for a paradigm shift in antiviral drug development: potentially drug targeting a human host protein, OSBP, that is required for viral proliferation of a broad-spectrum of RNA viruses, as opposed to targeting viral proteins present in individual viruses. We have discovered that transient, low dose treatment with the OSBP-targeting compound OSW-1-compound induces a longterm, multigenerational repression of OSBP, and the cells with repressed OSBP show a pronounced inhibition of ssRNA viral replication. Our preliminary results show that the OSW-1- compound has prophylactic antiviral activity at low nanomolar concentrations against several ssRNA viruses, including against one coronavirus tested. The longterm repression of OSBP, triggered by OSW-1, has no effect on cellular division, viability, or morphology. The purpose of this proposal is to understand the cellular role of OSBP in innate antiviral response. Our preliminary results show that OSBP: 1) regulates mTORC1 activity, 2) induces autophagy; 3) slows global protein translation; and 4) activates alternative splicing nonsense- mediated decay (AS-NMD) process, which is an RNA regulatory process. All of these OSBP- involved cellular processes would limit ssRNA viral replication individually, but there is little insight into the organization of these systems to establish a coordinated antiviral response.Our overall hypothesis is that OSBP serves in a major regulatory role to coordinate a multifaceted innate antiviral response to ssRNA infection. We propose a complete model of how OSBP senses early- stage viral infection and then triggers a multisystem response to block viral replication in cells, including through modulating mTOR1C activity and the AS-NMD system.",,2026,UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR,399717,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22179,5R01AI159290-02,The role of TRIM2 and SIRPA in New World Arenavirus entry,"New world hemorrhagic fever arenaviruses (NWAs), such as Junín virus, are rodent-transmitted viruses that cause ~30% mortality when they zoonose into humans. The mechanism by the NWAs induce disease is still not certain, although it likely includes induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Survivors of Junín infection develop strong humoral immune responses, suggesting that controlling infection at early times post-infection is critical for virus clearance. Although an effective Junín virus vaccine has decreased disease incidence, sporadic cases of this as well as the other known and novel NWAs for which there are no vaccines or effective therapeutics still occur. It is well-established that the clade B pathogenic NWAs bind to transferrin receptor 1 and other receptors on the cell surface, but the steps leading to their entry from an acidic cellular compartment are not well-determined. We recently performed a siRNA screen with pseudotyped viruses bearing a pathogenic Junín glycoprotein with the goal of finding host genes involved in entry that could serve as therapeutic targets. We found that TRIM2, a member of the tripartite motif family that includes well-known members of the host's intrinsic defense against viral infections, limits NWA endocytosis into cells. By probing the TRIM2 interactome for other host proteins that block NWA infection, we discovered that SIRPA, a cell surface protein that inhibits macrophage phagocytosis of tumor and dead cells and erythrocytes, also decreases infection. Importantly, SIRPA, unlike TRIM2, inhibits infection by various human pathogenic viruses that require trafficking to an acidic compartment, including VSV, Zika virus, LCMV and Ebola and SARS-Cov-2 pseudoviruses. Our data suggest that TRIM2 and SIRPA act at the viral entry/internalization step. These finding suggests that there are common mechanisms that regulate virus endocytosis and phagocytosis. We propose here to further investigate the overlap between virus-mediated endocytosis and phagocytosis in vitro, ex vivo and in vivo in three aims that will 1) investigate the overlap in the NWA entry and phagocytosis pathways; 2) determine where TRIM2/SIRPA inhibition of infection occurs; and 3) use TRIM2, SIRPA and other relevant knockout mice to probe the roles of these proteins in cell-type specific and in vivo infection by replication-competent NWAs. In addition to providing mechanistic insight into the entry of NWAs into cells, these studies have the potential of increasing our understanding as to how host factors limit infection and could lead to new approaches to therapeutic intervention.",,2027,UNIVERSITY OF ILLINOIS AT CHICAGO,493835,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P22180,5R01HL151498-04,Immunotherapy for acute lung injury secondary to influenza,"PROJECT SUMMARY/ABSTRACT The emergence of drug-resistant strains of human influenza A (IAV) and B viruses, as well as avian H5N1 virus with pandemic potential, to the only approved antiviral agents underscores the importance of developing novel antiviral strategies. We have engineered electrostatic complexes between cationic nanoparticles (i.e., chitosan) and anionic RNA that target airway epithelial cells in vivo during an IAV infection. These nanoplexes induce antiviral bioactivity directed against IAV in vivo with little or no untoward cellular or pulmonary responses. The nanoplex constructs stimulate early type I interferon (IFN) cellular responses through 5’- triphosphate (PPP)-RNA binding of the intracellular sensor, RIG-I. Additionally, the 5’PPP-NS1shRNA nanoplex formulation suppresses the translation of the IAV virulence factor, NS1, which inhibits RIG-I and host cell RNA maturation. The lung is well suited for an antiviral nanoplex strategy since it provides a portal for inhalation administration of bioactive nanoplexes. We have demonstrated that this strategy inhibits in vivo IAV replication therapeutically and avoids the “IFN paradox”, specifically, decreasing IAV lung injury, and IAV impairment of bacterial clearance from the lung. The focus of the current proposal is to optimize the therapeutic action of the 5’PPP-NS1shRNA nanoplex formulation in vitro and then in vivo. Additionally, we propose to carry out experiments recommended by the FDA article entitled “Antiviral Product Development: Conducting and Submitting Virological Studies to the Agency.” This includes in vitro and in vivo experiments to assess therapeutic efficacy (antiviral activity), pharmacokinetics, drug-drug interactions, and development of viral resistance. Additionally, because the 5’PPP-NS1shRNA nanoplex modulates the immune response, the FDA recommends examining possible unintended adverse effects resulting from actions on the immune system. Thus, we will also identify the specific immune system components that are altered, as well as assess the immune-mediated complications of an IAV infection including increased severity of the respiratory tract injury, and the risk of IAV-associated secondary bacterial pneumonia, a major cause of death in influenza cases. Specifically, we will examine the ability of 5’PPP-NS1shRNA nanoplexes to stimulate innate antiviral immunity, thereby changing infiltration of inflammatory cells, inflammatory cytokine milieu, adaptive immune responses, as well as decrease respiratory injury and IAV-associated impairment of bacterial clearance. In addition to assessing the clearance of IAV from the respiratory tract, we predict that the nanoplex construct will reduce the morbidity and severity of symptoms of influenza from drug resistant seasonal and pandemic strains, the highly pathogenic H1N1 swine-origin IAV virus (S-OIV) and H5N1 “bird flu”. These nano-technological approaches can also potentially treat other infectious (i.e., Ebola) or non-infectious lung injuries. Our proposal is designed to produce a novel antiviral nanoplex formulation for Phase 1 clinical trials as an Investigational New Drug.",,2025,STATE UNIVERSITY OF NEW YORK AT BUFFALO,436772,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H5,H1N1,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +P22181,3R01AI154274-03S1,Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach,"The current COVID-19 crisis starkly illustrates the need to develop new modalities for the therapeutic treatment of pathogenic single-stranded RNA (ssRNA) viruses, including against novel viruses that have yet to emerge. Human oxysterol-binding protein (OSBP) has recently been determined to be a critical mediator in the replication of a broad spectrum of ssRNA viral human pathogens, including the enteroviruses, rhinovirus, hepatitis C, Zika virus, Dengue fever viruses, and coronaviruses. OSBP is an ER-located, non-enzymatic protein reported to function as an important lipid sensor and lipid transporter in eukaryotic cells. Published research, including our own recent publications, has established the antiviral activity of structurally-diverse OSBP- targeting small molecules against multiple RNA pathogenic viruses. These discoveries present the opportunity for a paradigm shift in antiviral drug development: potentially drug targeting a human host protein, OSBP, that is required for viral proliferation of a broad-spectrum of RNA viruses, as opposed to targeting viral proteins present in individual viruses. We have discovered that transient, low dose treatment with the OSBP-targeting compound OSW-1-compound induces a longterm, multigenerational repression of OSBP, and the cells with repressed OSBP show a pronounced inhibition of ssRNA viral replication. Our preliminary results show that the OSW-1- compound has prophylactic antiviral activity at low nanomolar concentrations against several ssRNA viruses, including against one coronavirus tested. The longterm repression of OSBP, triggered by OSW-1, has no effect on cellular division, viability, or morphology. The purpose of this proposal is to understand the cellular role of OSBP in innate antiviral response. Our preliminary results show that OSBP: 1) regulates mTORC1 activity, 2) induces autophagy; 3) slows global protein translation; and 4) activates alternative splicing nonsense- mediated decay (AS-NMD) process, which is an RNA regulatory process. All of these OSBP- involved cellular processes would limit ssRNA viral replication individually, but there is little insight into the organization of these systems to establish a coordinated antiviral response.Our overall hypothesis is that OSBP serves in a major regulatory role to coordinate a multifaceted innate antiviral response to ssRNA infection. We propose a complete model of how OSBP senses early- stage viral infection and then triggers a multisystem response to block viral replication in cells, including through modulating mTOR1C activity and the AS-NMD system.",,2026,UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR,33183,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22182,1U01AI175008-01,HIV-1 Env gp160 maturation in the Golgi apparatus,"HIV-1 envelope (Env) glycoprotein (gp) 160 belongs to class I fusion proteins that are also expressed by other highly pathogenic human viruses including influenza A viruses (IAV), Ebola viruses (EBOV), and coronaviruses (CoV) such as SARS-CoV (SARS1), MERS, and SARS-CoV-2 (SARS2). They build spikes on the viral envelope that induce fusion of viral and cellular membranes to allow viruses to enter cells, which is essential to the viral infection. Class I fusion proteins are synthesized as a type I transmembrane (TM) polypeptide precursor in the endoplasmic reticulum (ER) and delivered to the Golgi apparatus for maturation. The Golgi contains glycosidases/glycosyltransferases for glycosylation and conserved oligomeric Golgi (COG) complex and other associated proteins such as soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins for trafficking. Inside the Golgi, high-mannose-type N-glycans are processed into complex- type and hybrid-type N-glycans after extensive mannose-trimming, and O-glycosylation also occurs. These precursors except for SARS1-spike (S) are further subjected to proteolytic cleavage by furin to complete the maturation process. When these steps are disrupted in the Golgi, no infectious particles are produced, leading to complete inhibition of viral infection. Recently, we and others reported that MARCH8, a member of the membrane-associated RING-CH-type E3 ubiquitin ligase family, broadly inhibits viral replication by targeting a wide range of fusion proteins. Importantly, we reported that MARC causes multiple defects in class I H8 fusion maturation in the Golgi via an unknown mechanism. These defects are found not only in furin-cleavage of HIV-1 gp160, IAV-hemagglutinin (HA), EBOV-glycoprotein (GP), MERS-S, and SARS2-S, but also in N- and O-glycosylation of SARS2-S, MERS-S, and EBOV-GP in the Golgi. Although MARCH8 does not trigger the degradation of these fusion proteins, its E3 ligase function is still required for causing these defects. The goal of this project is to elucidate the molecular mechanism of these multiple defects in HIV-1 gp160 maturation by understanding the MARCH8 antiviral mechanism. We hypothesize that MARCH8 targets glycosidases, glycosyltransferases, furin, COG complex, and/or SNARE to block HIV-1 gp160 maturation. We propose two distinct but inter-related Aims to test this hypothesis. In Aim 1, we will characterize how MARCH8 blocks gp160 maturation during HIV-1 infection. Experiments will be performed in primary cells and human T cell lines in combination with RNA silencing and CRISPR/Cas9 knockout to elucidate the MARCH8 anti- HIV activity. In Aim 2, we will identify the MARCH8 targets that play a critical role in HIV-1 gp160 maturation. We will focus on 18 Golgi proteins selected by high confidence bioinformatic analysis to identify the targets. The significance of this project is very high, which will not only fill in gaps in our understanding of class I fusion protein glycosylation and trafficking in the Golgi, but also elucidate a novel antiviral mechanism that can be broadly applied to several highly pathogenic human viruses including HIV-1, SARS2, EBOV, and IAV.",,2028,UNIVERSITY OF ILLINOIS AT CHICAGO,399750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Orthomyxoviridae,Unspecified,,,,,,,,Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2023 +P22183,5R21AI169309-02,Defining the optimal type and timing of COVID-19 vaccine in pregnancy,"PROJECT SUMMARY/ABSTRACT Pregnant individuals are more likely to require invasive mechanical ventilation or die from complications related to coronavirus disease 2019 (COVID-19) than non-pregnant women. COVID-19 vaccination in pregnancy can prevent the consequences of infection for the mother and provide passive immunity to newborns through placental transfer of vaccine-induced antibodies. The maternal immune system undergoes adaptive changes during pregnancy characterized by both active suppression of immune responses against the developing pregnancy and pro-inflammatory signals to promote healthy implantation and initiate labor. The central hypothesis is that the adaptive immunologic changes in pregnancy lead to differences in the development of vaccine-induced immunity depending on the gestational age at vaccination and/or the vaccine platform used. The overall objective of this proposal is to address important knowledge gaps including limited information regarding cellular immune responses following maternal vaccination, immune responses after vaccination in early pregnancy, and comparison of immunogenicity across different vaccine platforms. The research proposed is innovative because we will use a comprehensive immune profiling approach to quantify functional cellular and antibody responses in order to define the COVID-19 vaccine type and timing that optimizes robust and durable maternal vaccine-induced immunity (Aim 1) and neonatal passive immunity from placental transfer of viral neutralizing antibody (Aim 2). The proposed research is significant because it is expected to provide data to inform clinical recommendations for COVID-19 vaccines in pregnancy to improve maternal and neonatal outcomes. The long-term goal will be to provide preliminary data for a larger study evaluating vaccine efficacy for pregnant individuals and their neonates. The knowledge provided by this proposal will also inform future vaccine development for other important and emerging pathogens in pregnancy.",,2024,BETH ISRAEL DEACONESS MEDICAL CENTER,259350,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine design and administration | Characterisation of vaccine-induced immunity,2022 +P22184,5R01HD102445-03,Childhood Outcome After In Utero ZIKV Exposure,"PROJECT SUMMARY Clinically normal children exposed to Zika-virus (ZIKV) in utero may evidence abnormal neurodevelopment during the first few years of life even in the absence of the severe phenotype of congenital Zika syndrome (CZS). This is an important problem because the majority of children with in utero ZIKV exposure do not develop CZS but are at risk for neurodevelopmental abnormalities as they mature. The risk for neurodevelopmental impairments at school age in children with in utero ZIKV exposure, who do not have CZS, is not known because children have neither reached nor been studied at this critical age. The long-term goal is to recognize the spectrum of neurologic outcomes for children exposed to ZIKV in utero, which will enable appropriate follow-up guidelines, educational interventions, and therapies to support all children exposed to ZIKV. The objective of this application is to identify school age abnormalities in neurodevelopment and the domains affected and to evaluate for brain structural and functional differences among children in Colombia and in the US with ZIKV exposure in utero who do not have CZS. Guided by strong preliminary data, we will test two specific hypotheses: 1) that executive and motor function will be negatively impacted in ZIKV-exposed children compared to controls; and 2) that quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls. The children will be followed at age 5 and 7 years using a specifically designed set of neurodevelopmental assessment tools and quantitative structural and functional neuroimaging. Neurodevelopment will be assessed by an approach utilizing validated questionnaires and child assessments that measure executive function, behavior, motor function, and intellectual ability. The advanced brain MRI will provide a multimodal assessment of brain structure and function. The approach is innovative because of access to two uniquely well characterized cohorts, one from the Caribbean coast of Colombia who had sequential fetal and neonatal neuroimaging and had early neurodevelopmental evaluations and a cohort from a congenital Zika program in the United States with exposure by travel or emigration. The proposed research is significant, because it will address a key question in child health by focusing on neurodevelopmental abnormalities in children following in utero ZIKV exposure that can manifest at school age. Ultimately, such knowledge has the potential to immediately inform the development of guidelines for neuropsychological and imaging assessment at school age for children with in utero exposure to ZIKV. Completion of the aims will improve identification of abnormal neurologic outcomes in children who had exposure to ZIKV in utero. The knowledge to be gained from this work is essential to be done now and is important to families, care providers, public health policy authorities, and federal agencies. It may be also applicable to future congenital infectious epidemics and potentially other perinatal exposures.",,2025,CHILDREN'S RESEARCH INSTITUTE,688811,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +P22185,5R01EY032495-02,Role of Zika virus (ZIKV) infection in glaucoma pathobiology,"PROJECT SUMMARY The overall goal of this project is to investigate the role of Zika virus (ZIKV) in glaucoma pathobiology. ZIKV is an emerging viral pathogen that causes microcephaly and leads to severe ocular complications in newborns born to ZIKV infected mothers. Although the ocular manifestations of ZIKV are primarily reported to affect the posterior segment of the eye resulting in chorioretinal atrophy, withering of the retina and choroid, and optic nerve abnormalities, several clinical case reports showed the involvement of the anterior segment resulting in glaucoma. Studies from our laboratory, as well as those of others, have shown that ZIKV can cause glaucomatous pathology including an increase in intraocular pressure (IOP), retinal ganglion cell (RGC) loss, and optic nerve damage. The offspring of ZIKV infected dams have shown increased IOP and RGC loss and the presence of anti-flavivirus-antibody in these mice correlates with significantly enhanced glaucoma pathology due to antibody-dependent enhancement. Until the recent ZIKV epidemics, glaucoma has been primarily considered as a genetic and age-related disease and has not been reported among infants exposed to infection during gestation. Several studies have now reported that ZIKV can cause congenital glaucoma in infants born from mothers who were infected during pregnancy. Considering the fact that there is an endemic transmission of ZIKV in >84 countries, it is imperative to investigate the link between ZIKV and glaucoma to develop new prognostic and therapeutic tools to combat this global health threat. Our laboratory has developed several in vitro and in vivo models to study the pathobiology of ocular ZIKV infections. In our recent study, we reported that ZIKV can infect and replicate in human primary Trabecular Meshwork cells (HTMC). More recently, we performed RNAseq analysis and discovered that ZIKV infection of HTMC leads to transcriptomic alteration and dysregulation of several pathways including those that modulate ER stress response, autophagy, hypoxia, and ECM organization. Furthermore, ZIKV-infected mice exhibited increased IOP, ER stress, and autophagy in the anterior segment of the eye. ZIKV infection also caused RGC death and loss of RGC and optic nerve damage leading to disruption of anterograde axonal transport. Based on these novel findings, we hypothesize that ZIKV induces ER stress and autophagy resulting in TM death and dysfunction, increased IOP, and the development of glaucoma. Two specific aims are proposed to test this hypothesis. Aim 1 will determine the role of ZIKV induced ER stress in TM dysfunction and the pathobiology of glaucoma using C57BL/6 (WT) and IFNAR1-/- mice/pups and whether the reduction of ER stress alleviates ZIKV induced glaucomatous pathology. Aim 2 will investigate the role of autophagy using HTMC, and mouse models and evaluate the therapeutic efficacy of an FDA approved drug, hydroxychloroquine (HCQ) in ZIKV induced glaucoma. The anticipated results will establish the role of ZIKV infection in the pathogenesis of glaucoma and elucidate the molecular mechanisms and pathway-mediated therapeutic targets for future treatments.",,2026,UNIVERSITY OF MISSOURI-COLUMBIA,364633,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2021 +P22186,5R01AI149486-03,Understanding the mechanisms of antibody-mediated transcytosis of ZIKV within the placenta,"Humoral immunity is an essential component of the immune response to flavivirus infection. Primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly apparent that secondary infection with a closely related flavivirus strain can result in immunological cross-reactivity; however, the consequences to infection outcome are hotly debated and controversial. Zika virus (ZIKV) is a mosquito-borne flavivirus, which has a high degree of sequence and structural homology to Dengue virus (DENV), and is responsible for continuing epidemics of fetal congenital malformations within the Americas since its introduction to Brazil in 2015. Prior flavivirus exposure has been strongly associated with generation of cross-reactive antibodies that bind to and/or neutralize ZIKV. A unique aspect of ZIKV pathogenesis is the ability of the virus to seed infection within the placenta, however, the mechanisms of transplacental ZIKV infection are not well understood. The overall goal of this proposal is to understand how cross-reactive antibodies facilitate ZIKV transcytosis and seed infection of the placenta. The placenta is composed of anchoring chorionic villi, which penetrate the uterine wall, as well as floating chorionic villi that are bathed in maternal blood pooling in the intervillous space. Recent epidemiological observations found that between 20-50% of pregnant women with possible ZIKV exposure had detectable ZIKV RNA in the placenta. Another report found that ZIKV can persist in the placenta for over 200 days post mother onset of Zika symptoms. We discovered that Hofbauer cells, fetally- derived placental macrophages located within the villus stroma, are permissive for ZIKV infection. To identify a potential mechanism by which ZIKV gains access to the villous stroma, we recently evaluated the impact of cross-reactive dengue antibodies in mediating transplacental infection. Using an ex vivo placental explant model, we observed profound enhancement of ZIKV infection of human mid-gestation floating chorionic villi with ZIKV immune complexes generated using either DENV or ZIKV cross-reactive convalescent serum or monoclonal antibodies. Similar to histological analysis of placenta from infected pregnant mothers, ZIKV replicated exclusively within Hofbauer cells. Based on these observations, we hypothesize that the Fab fragment (specificity for ZIKV) and the Fc domain (affinity for FcRn and FcγR) of IgG impacts antibody-mediated ZIKV transplacental infection. Moreover, we believe that gestational age of the placenta dynamically influences the efficiency of ZIKV transcytosis and placental infection. Moreover, we believe that gestational age of the placenta dynamically impacts ZIKV transcytosis and placental infection. In this proposal, we seek to address the following outstanding questions: 1) How does IgG antibody specificity, affinity and Fc/FcRn interactions impact ZIKV transplacental infection? and 2) How does placental gestational age impacts antibody-mediated infection of Hofbauer cells? Our studies will likely reveal therapeutic targets and provide insights for development a vaccine to protect against ZIKV infection.",,2025,EMORY UNIVERSITY,756174,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P22187,5K01MH123258-03,Evaluating risks of ZIKV co-infection in SIV-infected macaques,"PROJECT SUMMARY Over 36 million people are living with HIV and there is large geographic overlap for areas endemic with flavivirus infection. Despite the occurrence of large flavivirus outbreaks, there is a severe lack of knowledge regarding the impact flavivirus infections may have on people living with HIV (PLWH). It is unclear what effect HIV co-infection has on the clinical consequences of flavivirus infection and current studies in humans are limited by low patient numbers and inconsistent incorporation of HIV disease status into interpretations of flavivirus disease. Non- human (NHP) models of Zika virus (ZIKV) infection recapitulate several aspects of human disease and are ideal for evaluating the impact of human flavivirus infection in people living with HIV. However, no established HIV- ZIKV co-infection animal model exists. In this proposal, we will study the natural history of HIV co-infection with flaviviruses to understand the risks, causes, and clinical outcomes in PLWH. Previously in NHPs, we showed that CD16+ monocytes are the major in vivo blood targets of ZIKV and similar results have been found in humans. Monocyte frequencies increase during HIV infection and although ART reduces total frequencies in HIV infected persons, CD16+ monocytes remain elevated. We will investigate the hypothesis that HIV infection promotes susceptibility to flavivirus infection by decreasing anti-viral innate and adaptive immune responses, increasing inflammation, and expanding cellular targets of infection, including monocytes. HIV invasion of the central nervous system (CNS) is mediated by CD16+ monocytes, therefore monocytes could also act to spread ZIKV to the CNS and promote neurological disease. Thus, HIV infection could promote ZIKV pathogenesis and neuroinvasion by expanding the cellular target pool and inducing inflammation. Additionally, we hypothesize that enhanced ZIKV pathogenesis occurs in PLWH, and we will experimentally test this using an NHP model of SIV infection. Specifically, in Aim 1 we will evaluate whether cells from SIV infected animals support greater ZIKV replication. In Aim 2 we will determine whether ZIKV pathogenesis is enhanced in SIV-infected macaques. We will determine whether SIV infection promotes invasion of ZIKV into the CNS and determine the innate and adaptive immune responses corresponding to enhanced infection. These studies will provide significant insights into the potential risk of enhanced ZIKV pathogenesis in the HIV population and determine if PLWH have a greater risk of ZIKV-associated pathologies. The goal of this K01 is to support the transition of developing my own independent research program focused on understanding the impact of viral co-infections in PLWH. In order to achieve this goal I will expand upon my previous training using NHP models of HIV and ZIKV human infection, will leverage the resources at the University of Washington and the Washington National Primate Research Center, and will work closely with my mentors, Dr. Deborah Fuller and Dr. Michael Gale.",,2024,UNIVERSITY OF WASHINGTON,67508,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease models | Disease pathogenesis",2020 +P22188,1R21AI149385-01A1,ADAR1-mediated antiviral response in Zika virus (ZIKV) infection,"Project Summary In response to viral infections, host cells trigger an innate/anti-viral immune response, predominantly by producing the interferons (IFNs) and IFN-stimulated genes (ISGs). These anti- viral responses promote inflammation, immune cell activation, and viral clearance. We recently reported that retinal pigment epithelium (RPE) and retinal vascular or choroidal endothelium are highly permissive to Zika virus (ZIKV) infection and elicit antiviral response with increased production of IFNs and ISGs. The transcriptomic analysis of ZIKV-infected RPE revealed the induction of adenosine deaminases acting on RNA1 (ADAR1), a potent ISG, which can exert pro- or antiviral activity by A-to-I editing of the host and viral RNA. The role and mechanisms of action of ADAR1 during ZIKV and related flaviviruses have not been studied till now. Our preliminary studies show that 1) ADAR1 is up-regulated at the transcript, as well as, protein levels upon ZIKV infection in RPE cells, and 2) ADAR1 overexpression reduced, while ADAR1 knockdown increased, ZIKV replication in RPE cells. These findings led us to investigate the role of ADAR1 in retinal innate immunity to ZIKV and other flaviviruses. Thus, the overall goal of this proposal is to determine the mechanisms of antiviral actions of ADAR1 in attenuating ZIKV replication in RPE cells (Aim 1); and to determine the consequences of ADAR1 ablation and ADAR1 overexpression on ZIKV-induced chorioretinal atrophy in a mouse model (Aim 2). The proposed studies will broaden and deepen our knowledge of the antiviral response during ocular ZIKV infection. Our studies could also identify new targets and treatment modalities based on the RNA editing ability of the host.",,2024,WAYNE STATE UNIVERSITY,231000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22189,5R21MH125034-02,Maternal ZIKV infection as an environmental risk factor for mental illness,"Abstract A large body of evidence has identified maternal immune activation following viral infection as an environmental risk factor for mental illness. Maternal immune signals, including inflammatory cytokines, can access fetal tissues and permanently alter brain function and behavior in otherwise developmentally normal offspring. Indeed, maternal infection with a number of viruses has been associated with the development of mood disorders and/or psychosis in offspring, and these associations are intensified in offspring with preexisting genetic risk factors for mental illness. Zika virus (ZIKV) is an emerging pathogen recently identified as an etiologic agent of severe neurodevelopmental syndromes following infection during the early stages of gestation. However, the impacts of maternal ZIKV infection during late gestation have not been adequately addressed, nor has the potential impact of maternal ZIKV infection on the mental health of developmentally normal offspring been investigated. Here, we propose to use a murine model of late-term maternal ZIKV infection to characterize neuroimmune signaling at the maternal-fetal interface. To study the consequences of this signaling, we will also assess the impact of late-term maternal ZIKV infection on the development of behavioral abnormalities in motor, cognitive and social domains that underlie psychiatric disorders (e.g., autism, schizophrenia). Finally, we will use an established mouse model of human 22q11.2 deletion syndrome, a common genetic susceptibility factor for mental illness, to examine interaction effects of maternal ZIKV infection with genetic risk for behavioral abnormalities. These studies will establish the potential pathologic behavioral consequences of late-term ZIKV infection, informing future study and monitoring efforts for individuals affected by this globally emerging pathogen.",,2024,"RUTGERS, THE STATE UNIV OF N.J.",186447,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Post acute and long term health consequences",2021 +P22190,5R01AI148264-03,Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates,"Abstract Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that recently caused an outbreak in the Americas. The establishment of ZIKV transmission cycle in tropical/sub-tropical regions that are endemic to other close-related flaviviruses such as Dengue virus (DENV) has raised concerns, mainly by their cross-immunological interactions and the implications of this for development of severe clinical manifestations. Several groups have demonstrated that DENV-immune serum from humans can enhance ZIKV infection in vitro and in vivo in an immunodeficient mice model. This phenomenon known as Antibody Dependent-Enhancement (ADE) has been linked to severe dengue clinical manifestations. Little is known about the effect of a previous immunity to ZIKV on a subsequent DENV infection. It is highly necessary to characterize correlates of protection in the control of a heterologous secondary DENV or ZIKV infection in the presence of previous DENV or ZIKV immunity in an immunological competent animal model that resemble the human immune system like the Non- Human Primates. Our group have preliminary data showing a potential protective role of the cellular immune response in dengue- immune or ZIKV-immune subjects during a heterologous secondary infection with ZIKV or dengue. The overall hypothesis behind this work is that the cross-primed cellular immune response may be critical controlling the DENV and ZIKV infection and provides heterologous protection against each other. To test this hypothesis, we propose a series of straightforward experiments by depleting the CD4+ or CD8+ or CD20+ cells at different time points before a primary or a secondary infection with dengue or ZIKV. This type of experiment has not been performed before in NHP. For these experiments we will use rhesus macaques bred and housed at the Caribbean Primate Research Center that has proven to be the purer Indian-origin macaque population of all populations in the USA or imported animals, without having a significant level of inbreeding. For first time in any study in the flavivirus field, we will use a large data on the MHC typing of this population to characterize specific CD4 and/or CD8 T cells epitopes playing a role in the T cells immune response against dengue and ZIKV. Understanding correlates of protection between ZIKV and DENV is essential to anticipate the outcome of the secondary infection, the design of diagnostics methods and more relevant, to support the design of highly effective ZIKV and DENV vaccines in the scenario of previous DENV or ZIKV immunity, respectively. Undoubtedly, NHP provide us with a unique immunological tool very close to the human system to provide the answers to the questions we are outlying on this application.",,2024,UNIVERSITY OF PUERTO RICO MED SCIENCES,685020,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22191,5R01AI150837-03,Enhanced susceptibility to Zika virus during pregnancy: a role for maternal dengue antibodies,"Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is closely related to dengue virus (DENV). Since its discovery in 1947, ZIKV remained relatively unnoticed, causing small, local outbreaks primarily in parts of Africa and Asia, and was associated with minor symptoms, such as mild fever. However, in the last decade, ZIKV started to spread geographically across the Pacific islands, eventually reaching South America, where it caused an explosive outbreak that started in Brazil in 2015 and rapidly spread to other South and Central American countries. This has been accompanied by a startling link between ZIKV infection during pregnancy and the development of birth defects among fetuses and babies, including microcephaly. It is unclear what factors may have led to the massive ZIKV outbreak or the severe disease manifestations in the Americas, but one potential variable is that much of the at-risk population in the Americas has preexisting immunity to DENV. It is well documented that preexisting immunity to one serotype of DENV can alter the disease pathogenesis of a subsequent infection with a different DENV serotype, a phenomenon called antibody-dependent enhancement (ADE). Because ZIKV outbreaks have occurred in regions around the world where DENV is endemic and due to the high degree of relatedness of ZIKV and DENV, it is critical to understand and characterize the extent to which prior infection with DENV exacerbates ZIKV disease. In this application, we will focus on how DENV antibodies impact ZIKV infection in the context of pregnancy by utilizing three model systems (immunocompromised Stat2-/- mice, immunocompetent humanized STAT2 knock-in mice, and human placental explants infected with ZIKV ex vivo).",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,421878,Animals | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2020 +P22192,5U01AI153416-02,"Living in the post-Zika world: Impact of interactions between dengue and Zika viruses on diagnostics, antibody dynamics, and correlates of disease risk","SUMMARY Worldwide, over 3 billion people are at risk of infection and disease caused by dengue virus 1-4 (DENV1-4) and Zika virus (ZIKV), both potentially severe flaviviral diseases transmitted by Aedes mosquitoes. The devastating effects of endemic dengue across the tropics and subtropics are well documented. The recent Zika pandemic galvanized research as Zika swept across Latin America. Three years after the peak of the Zika pandemic, major dengue epidemics have started to re-occur; however, the future of flaviviral disease across areas with widespread ZIKV immunity is unknown. In this R01, we propose to develop new tools and address key knowledge gaps in flaviviral transmission and immunological interactions between DENV and ZIKV to understand how widespread ZIKV immunity impacts subsequent dengue disease and to inform evaluation of dengue and Zika clinical vaccine trials and post-licensure studies. Based on our serological, epidemiological, and clinical data to date, our overall hypothesis is that DENV1-4 and ZIKV are antigenically closely related and that immune interactions mutually affect transmission and disease severity. We will address this hypothesis with the ongoing Pediatric Dengue Cohort Study (PDCS, 2004-present), a community-based prospective cohort study in Managua, Nicaragua, following ~4,000 children, now in its 17th year. Samples from the PDCS, as well as companion studies in Managua, provide documented infection and disease data, as well as banked serum samples for over a decade before the arrival of ZIKV. The proposed study extends the cohort, ensuring that we are able to fully document the interactions of these viruses from the pre- to post-Zika eras. In Aim 1, we will develop innovative serologic tools based on glycan-fusion-loop-masked envelope proteins and new algorithms to distinguish DENV and ZIKV infection histories, critical for vaccination and epidemiological studies of dengue and Zika. We will then test our hypothesis that pre-existing ZIKV immunity can enhance disease severity caused by DENV3 but protect against DENV1. In Aim 2, we will measure changes in anti-DENV and anti-ZIKV antibody-mediated immunity over time, estimate annual changes in protective and enhancing population immunity to each virus, collect entomological data, and use modeling approaches to evaluate popula- tion susceptibility to DENV and ZIKV infection and the potential for future epidemics by incorporating immunolo- gical and entomological data. In Aim 3, we will identify determinants of protective and disease-enhancing anti- body-mediated immunity of prior DENV infection on Zika and prior ZIKV infection on dengue disease and severity. With support of expert collaborators, we will use state-of-the-art tools (e.g., new monoclonal antibodies, innovative flavivirus antigens, and antibody Fc profiling) to analyze specific infection histories and uncover potential immune correlates. Overall, this program will define new vaccine companion diagnostic assays, the dynamics of the antibody response to DENV and ZIKV, and correlates of protection and pathogenesis for dengue and Zika, which should be useful for the development and evaluation of dengue and Zika vaccines.",,2026,UNIVERSITY OF CALIFORNIA BERKELEY,978740,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences,2021 +P22193,5R01AI163188-02,Development of a Replicon RNA-based Vaccine against Dengue and Zika,"ABSTRACT The long-term goal of this project is to develop a dengue-Zika vaccine that provides protection against the four serotypes of dengue (DENV1-4) and Zika (ZIKV) viruses with maximal safety and efficacy. To date, flavivirus vaccine development has focused on the induction of neutralizing antibodies (nAbs), as they have been assumed to be the key mechanism for protection against natural infection. However, DENV and perhaps ZIKV are unusual in that weak Ab responses to vaccination or prior infection can induce antibody-dependent enhancement (ADE) of infection and pathogenesis during subsequent reinfections. In fact, DENV disease with severe sequalae has been documented in children given the only currently licensed DENV vaccine. Thus, the primary objective of this application is to develop an effective vaccine against DENV and ZIKV that cannot mediate ADE. We hypothesize that this vaccine will need to elicit both strong nAb responses and strong T cell effector responses that will counterbalance the presence of any ADE-mediating Abs, based on our work investigating the interplay between Ab and T cell responses to DENV and ZIKV. In particular, we have shown that CD8 T cells mediate cross- protection against heterotypic DENV and ZIKV infections, and that DENV vaccine-elicited CD8 T cells can prevent ADE. In addition, our preliminary data show that an RNA replicon-based vaccine expressing ZIKV nonstructural protein 3 elicits only T cell but not nAb responses and confers protection against ZIKV challenge in mice. Thus, we hypothesize that our combinatorial DENV-ZIKV vaccine expressing both Ab- and T cell-targeting proteins of DENV1-4 and ZIKV will produce humoral and cellular immune responses that provide robust, long-term protection against all five viruses. We will test this hypothesis by achieving the following Specific Aims: 1) To evaluate immunogenicity and efficacy of a DENV-ZIKV vaccine. 2) To determine the durability and mechanistic underpinnings of DENV-ZIKV vaccine-induced protective immunity.",,2026,LA JOLLA INSTITUTE FOR IMMUNOLOGY,712699,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P22194,5R01AI153130-03,Early neural predictors and neuropathogenesis of sensorimotor neurodevelopmental deficits in macaque infants exposed to Zika virus in utero,"PROJECT SUMMARY Prenatal exposure to the Zika virus (ZIKV) poses a threat to the fetus, putting the neonate at risk for significant birth defects (termed congenital Zika syndrome) and neurodevelopmental deficits developing during early child- hood. There are currently no predictors to indicate which children will develop deficits and the neuropathologies underlying these deficits is not defined. It is critical to predict which infants will later develop deficits to max- imize long-term sensorimotor development and functional outcomes. Furthermore, understanding underlying neuropathogenesis is necessary to develop targeted interventions. The purpose of this grant is to define the long-term neurodevelopmental outcomes of ZIKV by rapidly obtaining data from highly controlled studies of rhesus macaques. Specifically, we will: Aim 1: Characterize sensorimotor neurodevelopmental outcomes in macaques with prenatal ZIKV expo- sure. Behavioral assessments focused on sensorimotor development may highlight the distinct developmental trajectories and increased deficits with age in ZIKV-exposed rhesus macaques. Because macaques develop more quickly than humans, sensorimotor neurodevelopmental differences that occur by year 3 may predict future impacts in children born with prenatal ZIKV exposure. Aim 2: Identify early neural predictors of sensorimotor neurodevelopmental deficits in ZIKV-exposed infant macaques with quantitative MRI, hearing and visual studies. We will describe differences between ZIKV-exposed and mock-infection control infants and identify individual differences within ZIKV-exposed in- fants to determine the full spectrum of brain abnormalities. Aim 3: Define neuropathology underlying sensorimotor neurodevelopmental deficits with quantitative brain histopathology. Using cellular quantification and organization of brain nuclei, we aim to identify the neu- ropathogenesis of congenital Zika syndrome to better create appropriate, targeted interventions for children. This study utilizes a large cohort of ZIKV-exposed infant macaques that have been born in other NIH-funded studies and capitalizes on our collaborative team of experts in neuropathology, neurodevelopment and neu- roradiology.",,2025,UNIVERSITY OF WISCONSIN-MADISON,760916,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P22195,5R01NS120182-02,Neurodevelopment after postnatal Zika virus infection in infant macaques,"PROJECT SUMMARY / ABSTRACT Intense research has focused on the neurologic effects of prenatal Zika virus (ZIKV) infection; however, the consequences of postnatal infection early in life are understudied. Infants exposed to ZIKV in utero but born without microcephaly can develop postnatal microcephaly, neurologic dysfunction, and neurodevelopmental ab- normalities, highlighting the potential of ZIKV to cause ongoing damage after birth. This damage is likely related to the exponential maturation of the brain that occurs during the first 2 years of life, particularly in temporal, prefrontal and parietal regions important for emotional, social and executive functions, including learning, atten- tion and memory. Our group has previously reported that postnatal ZIKV infection causes abnormalities in brain structure, function, and behavior in a pilot study of infant rhesus macaques (RMs) infected postnatally. Here, we propose to extend the scope and duration our prior pilot study and generate novel data regarding the impact of postnatal ZIKV infection on the developing brain. The Objective of this application is to bring new mechanistic insights into postnatal ZIKV infection to address the existing knowledge gap regarding outcomes and host-virus interactions. We will use our postnatal ZIKV-RM model to interrogate the neurobehavioral impact of ZIKV infection at different stages of postnatal brain develop- ment, with approaches that span from single cells to whole animal. This model of postnatal ZIKV exposure allows us to generate key data on the mechanisms by which ZIKV and/or the immune response to infection leads to cellular changes that ultimately result in aberrant postnatal development of limbic structures and behavioral def- icits later in life. We hypothesize that 1) ZIKV and/or the immune response to infection disproportionately affects limbic structures in the postnatally developing brain; 2) cellular changes in these limbic structures lead to aberrant neurodevelopment and abnormal behaviors; and 3) there may be a period of vulnerability to ZIKV during post- natal brain development. We will test our hypotheses in these Specific Aims: 1) Determine the spectrum of abnormal behavior and cognition following ZIKV infection of infant RMs at different stages of brain development; 2) Identify developmental trajectories of brain structure and function following postnatal ZIKV infection of infant RMs at different stages of brain development; and 3) Define the neurodevelopmental pathways and cell types impacted by postnatal ZIKV infection. This work will include RM infants infected with ZIKV at 1 or 6 months of age (equivalent to 4 and 24 month old humans) as well as age- and rearing-matched and viral mimic controls, that over their first 2 years of life will undergo a series of detailed assessments including validated tests of soci- oemotional behavior and cognition, structural and functional brain imaging, brain histology, stereology and single cell and bulk cell transcriptomics. Our results may have important public health implications for children living in ZIKV-endemic/epidemic areas as well as for travelers to these regions.",,2025,EMORY UNIVERSITY,710393,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Post acute and long term health consequences",2021 +P22196,275201800001I-0-759402200003-1,STUDY CLOSEOUT FOR THE INTERNATIONAL COHORT STUDY OF CHILDREN BORN TO WOMEN INFECTED WITH ZIKA VIRUS DURING PREGNANCY (ZIP 2.0),"Zika virus (ZIKV) is an arbovirus (vector-borne virus) of the genus Flaviviridae. Infections were thought to be mild and self-limiting until 2015, when an epidemic was observed initially in Brazil of microcephaly and other birth defects in newborns following infection of the mother during pregnancy with ZIKV. Increasing evidence now points to ZIKV as the agent responsible for a variety of birth defects in newborns of mothers who become infected during pregnancy. The relationship of ZIKV infections in pregnant women with adverse outcomes of pregnancy is the subject of ongoing evaluation. Studies to date of infants born to infected women have tended to focus on those born with serious birth defects that constitute the congenital Zika syndrome (CZS), which has been shown in a recent population-based study from Brazil to increase risk of death in the first three years of life more than 11-fold compared to children without CZS1. The U.S. Zika Pregnancy and Infant Registry reports that approximately 5% of infants born to women with ZIKV infection during pregnancy have Zika-associated brain or eye defects2 consistent with CZS. But whether there are latent effects on growth and development in the 95% of infants who are born without CZS to Zika-infected women, and what those effects may be, remains to be elucidated. Longitudinal studies of infants born to Zika-infected pregnant women are needed to assess the broader spectrum and natural history of a wider range of possible manifestations of intrauterine or intrapartum Zika exposure. In 2016, NIH initiated a large, multicenter, international observational study of the epidemiology, natural history, and pathogenesis of Zika in infants and pregnancy, the Zika Infections in Pregnancy (ZIP) Study. The ZIP Study followed infants born to women at risk for Zika infection during pregnancy through just the first 12 months of life and completed its last patient last visit December 2019. In 2018, NIH initiated the International Cohort Study of Children Born to Women Infected with Zika Virus During Pregnancy (ZIP 2.0) of Zika exposed children and unexposed control children from the ZIP Study or similar studies, following the children through 42 months of age to evaluate the effects of Zika on child growth and development. Recent studies have found that infants who had in utero ZIKV exposure without CZS appear to be at risk for abnormal neurodevelopmental outcomes in the first 18 months of life3 and similarly observed high frequencies of anatomical and neurodevelopmental abnormalities in children without microcephaly who were exposed to ZIKV in utero4. One study found a gradient of risk of development delay according to head circumference, with severely microcephalic children at highest risk for delays while normocephalic ZIKV-exposed children showed similar risk to unexposed control children5. However, several other studies have observed abnormal neurodevelopment in the absence of microcephaly among children with intrauterine ZIKV exposure6,7. Those reports indicate that nearly all such children presented at least one developmental delay and that a significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities. This task order addresses NIH’s requirement to conduct an evaluation of the impact of prenatal Zika exposure among ZIP 2.0 infants and children. Given the variable and sometimes conflicting findings reported to date in the scientific literature, this task order will help to determine whether, to what extent, and what types of longer-term follow-up is indicated.",,2024,"WESTAT, INC.",499998,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2022 +P22197,5R01AI153433-03,A Novel Strategy for Generating Safe and Effective Flavivirus Vaccines,"The recent emergence and devastating impact of Zika virus (ZIKV) clearly demonstrates that arboviral emergence continues to defy accurate prediction and exposes our inability to rapidly respond to and control outbreaks. The medical and veterinary importance of emerging flaviviruses is significantly exacerbated by the absence of available vaccines, therapeutics, and reliable control measures. Vaccination remains the most reliable strategy for outbreak prevention and control, but vaccine development intrinsically involves trade-offs between safety and immunogenicity. This study will develop a platform to overcome these trade-offs by combining the safety advantages of non-replicating platforms with the rapid and long-lived immunogenicity of a live-attenuated vaccine. We have developed a unique chimeric virus platform based on a novel insect-specific flavivirus (ISFV), Aripo virus (ARPV). Preliminary data shows ARPV’s host restriction is noticeably later in the replication cycle than described for other ISFVs and is capable of entering vertebrate cells and developing a robust immune response in the absence of genomic replication. An ARPV/ZIKV chimera was developed to test our hypothesis that ARPV/ZIKV vaccination produces a rapid and robust innate, humoral, and cell-mediated immune response that elicits sterilizing immunity against subsequent ZIKV challenge. Preliminary studies show a single dose of ARPV/ZIKV produces a robust adaptive ZIKV-specific immune response that completely protects mice from viremia, weight loss, and mortality, while demonstrating exceptional safety in vivo. This platform is superior because of the increased safety of the chimera by virtue of its fundamental replication defect in vertebrate cells, increased immunogenicity due to a lack of inactivation requirements, and efficient genome delivery to target cells. This innovative and essential R01 aims to evaluate the safety profile, protective efficacy and mechanisms underlying the immunogenicity of ARPV/ZIKV vaccination via three aims: 1. Determine the efficacy of ARPV/ZIKV immunization for preventing ZIKV-induced disease in murine and rhesus macaque models. 2. Elucidate the correlates underlying vaccine-induced protection from ZIKV-induced disease in ARPV/ZIKV vaccinated murine models. 3. Evaluate the safety profile of this vaccine candidate in vitro and in vivo, and elucidate the mechanism underlying its immunogenicity. This study will generate a safe, efficacious, single-dose ZIKV vaccine that will be ideally suited to affordably control explosive outbreaks, which typically affect resource-limited regions. Our platform’s antigenic superiority will result in enhanced efficacy, effectively combining the safety of replication-defective virus-like particles or nucleic acid vaccines with the antigenic superiority, and rapid, long-lived immunogenicity of live-attenuated vaccines. This platform can also be readily translated to other flaviviruses of human or veterinary importance.",,2025,VIRGINIA POLYTECHNIC INST AND ST UNIV,416856,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22198,5R01GM139823-02,How flaviviruses hijack a host transmembrane protein chaperone to promote viral infection,"Dengue virus (DENV) infection is the most common arboviral disease globally, with up to 400 million infections and 25,000 deaths annually. The related flavivirus Zika virus (ZIKV) has also spread rapidly across the tropics and subtropics, and outbreaks of both DENV and ZIKV infection have now reached the continental United States. There are currently no effective antiviral agents against either virus, no DENV vaccine approved for use in the United States, and no ZIKV vaccine. Our long-term goal is to comprehensively identify and characterize the cellular pathways required for flavivirus infection, as these may represent novel targets for antiviral treatment. We and others have identified the host Endoplasmic Reticulum Membrane Protein Complex (EMC) as required for infection by multiple flaviviruses, including DENV and ZIKV. The EMC appears to function as a molecular chaperone, promoting the biogenesis of multipass membrane proteins in the endoplasmic reticulum. However, how the EMC supports flavivirus infection is unknown. Strikingly, our published findings reveal that during infection, the EMC is required by flavivirus replication by promoting the biogenesis of flavivirus NS4A and NS4B at an early post-translational step. Both proteins are non-structural multipass transmembrane proteins essential for viral replication. The objective of this proposal is to define how the EMC supports DENV and ZIKV replication. Our central hypothesis, based on strong preliminary data, is that the EMC functions as a molecular chaperone for the proper biogenesis of select flavivirus-encoded multipass transmembrane proteins. This proposal leverages the complementary strengths of an investigator with extensive experience in flavivirus-host biology (Tai), and another in ER-quality control mechanisms hijacked during viral infection (Tsai). The specific aims of the project are to (1) Define and validate the viral determinants of EMC dependence; (2) Determine the specific role of the EMC in flaviviral replication; and (3) Characterize DENV and ZIKV mutants that bypass EMC dependency. Successful completion of this project will illuminate the mechanism by which the EMC supports flavivirus infection, thereby providing insights into a novel vulnerability shared by these medically important viruses. It will also increase our understanding of other viruses that require the EMC.",,2025,UNIVERSITY OF MICHIGAN AT ANN ARBOR,356140,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22199,5R21AI159643-02,Broad-spectrum inhibitors targeting the viral replication promoter conserved in dengue and Zika viruses,"Project Summary Zika virus (ZIKV) and dengue virus (DENV) are mosquito-borne flaviviruses that cause disease ranging in severity from mild symptoms to deadly hemorrhagic dengue fever. ZIKV was rapidly spreading five years ago to over 20 countries in South and Central America, where infections by ZIKV reached pandemic levels and threatened to expand to the southern US. The threat by DENV has increased dramatically over the last two decades as one of the worst mosquito-borne pathogens in tropical regions. To treat outbreaks of DENV in ZIKV-endemic regions, and vice versa, broad-spectrum inhibitor drugs against mosquito-borne flaviviruses would provide an efficient therapeutic approach that reduces the risk of immuno-associated exacerbation, for example in previously infected or vaccinated patients. Sequence alignment of DENV and ZIKV clinical isolates in combination with secondary structure prediction have led us to identify a conserved RNA three-way junction that serves as the replication promoter in flaviviruses. Here, we propose to identify compounds that inhibit viral replication by targeting the promoter RNA as lead candidates for the future development of DENV and ZIKV broad-spectrum therapeutics. The Specific Aims of this proposal are to 1) develop a FRET-based binding assay to assess small molecules as selective ligands of the DENV and ZIKV replication promoter RNA, 2) establish an in vitro replication initiation assay to identify promoter RNA-binding ligands as inhibitors of ZIKV replication, and 3) discover small molecules that inhibit DENV and ZIKV in cell culture by targeting the RNA 3WJ motif that serves as the viral replication promoter.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",193464,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22200,1R56AI170857-01,Molecular mechanisms linking viral replication and neuropathogenesis,"PROJECT SUMMARY/ABSTRACT Viruses that infect the developing brain, including Zika virus (ZIKV), rubella virus, and cytomegalovirus, cause major birth defects. Microcephaly is one such birth defect, in which head and brain size are severely reduced, and is often accompanied by intellectual disability. This virally-inflicted neurological disease, or viral neuropathogenesis, can be caused by multiple mechanisms. One recently identified mechanism by which ZIKV non-structural protein 4A (NS4A) causes microcephaly is by disrupting the human ANKLE2 protein. Interestingly, individuals with mutations in the gene encoding ANKLE2 suffer from microcephaly. ANKLE2 is conserved from worms to humans, and is essential for coordinating cell division during brain development. ANKLE2 is not an enzyme, and instead derives this function in cell division and development by mediating protein interactions. NS4A physically interacts with ANKLE2 and disrupts brain development in an ANKLE2-dependent manner in a fruit fly model of brain development. ANKLE2 also promotes ZIKV replication. Taken together, these studies show that in the process of coopting a host protein for replication, ZIKV dysregulates an important developmental pathway. Thus, the NS4A-ANKLE2 protein interaction represents an important model to study viral neuropathogenesis and how it is connected to viral replication and hereditary disorders at the molecular level. The long-term goal of this work is to decipher how virus-host protein interactions impact virus replication and pathogenesis, as these discoveries will fuel therapeutic target identification and drug development. The objective of this proposal is to dissect the mechanisms by which the protein interaction between ZIKV NS4A and human ANKLE2 promote ZIKV replication and inhibit brain development. To accomplish this objective, we will test the central hypothesis that ANKLE2 promotes viral replication through its interaction with NS4A and by recruiting other host factors involved in ZIKV replication to sites of replication, and this disrupts physiological ANKLE2 protein interactions required for brain development. The following specific aims will test this hypothesis: Aim 1: Dissect the impact of the NS4A-ANKLE2 protein interaction in ZIKV replication and pathogenesis. Aim 2: Unravel the molecular function of ANKLE2 in ZIKV replication and pathogenesis. When completed, this work will delineate how a single virus-host protein interaction rewires a developmental pathway to facilitate virus replication and inflict neurological disease at the molecular level. This will reveal detailed biochemical insight into a virus-host interaction with amino acid-level resolution, new host factors that play a role in ZIKV replication, and previously unknown proteins key to brain development. In the long term, the methods established here could be employed to uncover the molecular mechanisms behind other diseases with viral and hereditary etiologies.",,2023,UNIVERSITY OF CALIFORNIA AT DAVIS,528198,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P22201,1R01NS125778-01,Role of microglia in neural infection,"ABSTRACT Zika virus (ZIKV) infection is associated with congenital ZIKV syndrome (CZS), including various brain anomalies and microcephaly. Our recent studies suggested that yolk sac (YS)-derived microglia (primary immune cells in the brain) and Peli1 (an E3 ubiquitin ligase) are involved in ZIKV infection and its associated CZS. However, it is unknown whether and how Peli1 contributes to the YS-microglia-mediated spread of ZIKV into brain, whether viral infection affects the normal function of microglia, and how such effects influence neural differentiation. Based on preliminary data, we hypothesize that Peli1 plays a critical role in fetal brain ZIKV infection via promoting YS-microglia-mediated ZIKV dissemination into fetal brain and via altering microglial function to affect neural differentiation. This hypothesis will be tested by two specific aims: 1) to determine how Peli1 promotes ZIKV infection of YS-microglia and virus dissemination from microglia to neural stem cells in fetal brains; and 2) to determine how Peli1 mediates microglial activation and alters neural differentiation after ZIKV infection. This integrative study employs biochemical and genetic manipulations in both in vivo animal models and in vitro mouse and human cell platforms. The outcomes will be evaluated by molecular, cellular, and neuroanatomical analyses. Understanding the molecular mechanisms underlying the role of microglia in ZIKV-related brain infection may lead to identification of new targets for prevention and treatment of ZIKV and other virus-mediated congenital neural infections.",,2026,UNIVERSITY OF TEXAS MED BR GALVESTON,516055,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2022 +P22202,5R01EY032149-02,Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection,"PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pathology, including loss of foveal reflex and macular pigment mottling, chorioretinal scarring, and macular atrophy. ZIKV has become endemic and local transmissions in the USA have been reported previously. The long-term effects of structural damage on vision, as well as the pathogenic processes of congenital ZIKV eye diseases are beginning to be understood. The signaling pathways governing normal eye development, which are dysregulated during ZIKV infection, are not well characterized. We recently carried out a series of experiments by establishing a ZIKV infectious ocular cell culture system and mouse models to understand the structural and molecular perturbations. For successful replication, viruses have evolved various strategies to evade innate immune response as well as to enhance the availability of cellular metabolites required to meet the heightened energy demand for viral genome synthesis. We found that the AMPKα, a cellular master energy sensor, is activated in the ZIKV-infected retinal cells. Moreover, pharmacological activation of AMPK resulted in attenuated ZIKV replication. Another interesting finding is that the YAP/TAZ factors in the tumor suppressor Hippo/SWH signaling pathway were induced early on, but degraded at later stage of ZIKV infection in RPE cells. Silencing YAP/TAZ resulted in reduced ZIKV replication. Since the energy sensor AMPK and Hippo signaling pathways control key cellular processes, including host antiviral responses, it is critical to understand the fundamental mechanism of these two pathways deregulation. We hypothesize that ZIKV modulates AMPK and Hippo signaling pathways in ocular cells to 1) increase intracellular metabolic resources, and 2) inhibit TBK1 to antagonize antiviral defense. These molecular changes can be orchestrated through viral coded factors resulting in the pathogenesis of ocular cell injury. The following specific aims will be investigated. Aim 1 focuses on systematically evaluating the role of AMPK- Hippo signaling on regulating antiviral response to ZIKV infection in RPE cells. The cross talk between these pathways will be investigated at the YAP/TAZ level. Pharmacological activation/inhibition, and gene knockout approaches in RPE cells will be carried out. Aim 2 is designed to elucidate the effect of ZIKV on Hippo and AMPK signaling pathways during retinal development. Human iPSC-derived 3D-retinal cup organoids will be used to investigate the link between retinal development and ZIKV-mediated deregulation of these key pathways. The ZIKV-encoded virulence factors regulating these pathways will be characterized. Aim 3 is to determine the effect of RPE-specific ablation of AMPK, TBK1, and Hippo signaling on the pathogenesis of ZIKV-induced chorioretinal atrophy in mice. This proposed study would yield novel insights into the pathogenesis of ZIKV in ocular diseases and identification of potential therapeutic targets.",,2024,UNIVERSITY OF CALIFORNIA LOS ANGELES,504736,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2021 +P22203,1R01AI153724-01A1,Development of a vaccination platform for emerging flavivirus infections,"Project Summary: The Flavivirus genus (referred to as flaviviruses) consists of numerous emerging and re-emerging global pathogens of critical human significance. Endemic and emerging flaviviruses like dengue virus (DENV), Powassan virus (POWV), Zika virus (ZIKV), West Nile virus, Japanese Encephalitis virus and Yellow fever virus continue to spread and cause significant human disease. We have used RNA structural data from a conserved 3’ untranslated region (UTR) pseudoknot called xrRNA1 to develop an attenuation approach in a highly conserved structural region of the flavivirus 3’UTR for vaccine development. This approach allows us to 1) swap out flavivirus structural genes in our clone to rapidly develop chimeric, attenuated flavivirus vaccines for mosquito-borne flaviviruses and 2) provides a conserved site for attenuation for tick-borne flaviviruses like POWV. Based on our preliminary data, we hypothesize that xrRNA1-mutant, attenuated flavivirus vaccines will be safe, immunogenic, and provide protection from challenge in murine models of flavivirus disease. The objective of the proposed studies is to complete pre-clinical development of the attenuated flavivirus vaccine approaches. We will complete our proposed work in three aims that will evaluate immunologic and virologic outcomes following virus challenge after vaccination with candidate ZIKV vaccine (Aim 1), DENV vaccine (Aim 2), and POWV vaccine (Aim 3). We have recently published our data showing attenuation and immunogenicity of mutant xrRNA1 ZIKV (X1) in pregnant and non-pregnant mice. In this proposal, we will first evaluate the efficacy of ZIKV X1 vaccine in pregnant and non-pregnant mice challenged with ZIKV and DENV. These studies will allow us to evaluate ZIKV vaccine efficacy during pregnancy and evaluate the role of ZIKV vaccination in DENV disease enhancement. Next, we will use the attenuated, ZIKV vaccine platform developed in our laboratory using xrRNA1 structural data, insert chimeric pre-membrane and envelope structural genes from DENV1-4 and evaluate the attenuation, immunogenicity and efficacy of monovalent and quadrivalent DENV1-4 vaccine candidates. Given the complexity of DENV infection, we will evaluate disease enhancement and immunodominance in our quadrivalent vaccines along with efficacy. Third, we will expand our attenuation strategy in the X1 structure to tick-borne flaviviruses by utilizing our recently defined secondary structure of the POWV 3’UTR. Using POWV mutant vaccine candidates with targeted mutations in the X1 structure, we will characterize attenuation, immunogenicity, and efficacy of a POWV vaccine approach in a murine model of disease. The proposed studies will begin to translate our structural understanding of xrRNAs in the flavivirus 3’UTR into potential vaccine candidates. Moreover, this project will initiate studies focused on developing a platform for vaccine development for emerging flavivirus infections.",,2026,UNIVERSITY OF COLORADO DENVER,436523,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P22204,5K08AI150996-03,Innate Immunity of Zika Virus Infection In Human Neural Progenitors,"PROJECT SUMMARY / ABSTRACT The 2016 outbreak of Zika virus (ZIKV) in the Americas demonstrated how quickly and dramatically a mosquito-borne viral infection can affect human life. Like related flavivirus family members such as West Nile virus, ZIKV can invade and infect the central nervous system (CNS), but is unique in causing in utero infection which leads to developmental abnormalities including microcephaly. ZIKV seems to have a predilection for infecting neural progenitor cells (NPCs) and persists for months in the fetal CNS after in utero infection, which suggests an ineffective immune control of the virus. We hypothesize that impaired innate immunity in neural progenitor cells underlies increased susceptibility to infection by ZIKV and contributes to microcephaly. The innate immune system includes pattern recognition receptors (PRRs) that detect pathogens and signal through effector molecules including interferon (IFN), which drives the expression of hundreds of antiviral interferon-stimulated genes (ISGs). Using induced neural progenitor cells (iNPCs) as a model for fetal CNS development, we have identified key innate immune signals that are attenuated in neural progenitors compared to mature neurons and glia: the expression levels of retinoic acid-inducible gene I (RIG-I, a PRR that detects viral RNA); and the IFN-driven upregulation of two ISGs (IFIT1 and IFITM1). We now propose to extend these findings as follows: (1) we will define the developmental changes in expression and function of PRRs during neural differentiation using the iNPC system and an established embryonic stem cell line as a control; (2) we will use CRISPR knockout or overexpression of RIG-I in bulk iNPCs and in a cerebral organoid model to test whether insufficient RIG-I signaling underlies iNPC susceptibility to ZIKV infection and microcephaly; (3) we will perform single cell RNA-seq on ZIKV-infected neural progenitors, neurons and glia to identify differentially expressed genes and gene networks, revealing innate immune components that confer susceptibility or resistance to ZIKV; and (4) using CRISPR knockout or overexpression of IFIT1 and IFITM1 we will test the role of these proteins in limiting ZIKV infection in progenitors and cerebral organoids. These experiments will define key innate immune proteins that influence susceptibility or resistance to ZIKV, identifying therapeutic targets to protect the fetal brain during ZIKV infection. Dr. Stokes’ development plan builds on a background in neurosciences with coursework and hands-on training in immunology, neural stem cells, and bioinformatics. The proposal establishes a mentoring committee including faculty in immunology, neurosciences, and infectious disease to provide guidance and career development. A K08 award will allow Dr. Stokes to make maximal use of UW’s extensive scientific resources to achieve scientific independence, advancing his career goal to develop therapeutic interventions that protect neural function from injury during viral encephalitis.",,2025,UNIVERSITY OF WASHINGTON,195006,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2020 +P22205,4R00DE028573-04,Molecular regulatory mechanism of Zika virus-induced intracranial calcifications,"Project Summary/Abstract: The number of vector-borne disease cases in the US has tripled over the past decade and these pathogens including mosquito-borne Zika virus (ZIKV) remain an apparent threat to general public health. The ZIKV outbreaks in the Americas and Southeast Asia is a major global health concern, largely due to the association with fetal craniofacial abnormalities and malformations, resulting from prenatal infection. Although ZIKV infection during pregnancy is casually associated with microcephaly, it is important to note that intracranial calcification is the most frequent abnormality present in ZIKV-positive babies. In fact, Magnetic Resonance Imaging study of Brazilian large ZIKV-positive baby cohort reported the intracranial calcifications as the most common clinical observations. While calcification occurs in soft tissues, the abnormal deposition of calcium in brain not only severely affects motor function, speech ability, and vision, but also causes seizures. Despite the growing clinical evidences of ZIKV-induced calcifications and their potential dire outcomes, however, the etiology and molecular mechanisms of ZIKV-induced brain calcification remain elusive. My preliminary observations in ZIKV human fetal brain specimens showed that high level of calcium deposits was localized with virus-infected perivascular cells. Intriguingly, ZIKV-infection of brain perivascular and osteogenic precursor cells robustly induced calcifications in vitro. Surprisingly, the induction of calcification was lineage-specific to the Asian ZIKV strains, but not to the African ZIKV strains. African ZIKV strains rapidly replicated, inducing cell death, while Asian ZIKV strains persistently replicated, leading to aberrant calcium deposition. Surprisingly, ZIKV expression library screen showed that NS3 protease was sufficient to induce calcification. Based on these preliminary data, I hypothesize that ZIKV targets specific host brain perivascular cells and utilizes NS3 protease to induce intracranial calcifications, which ultimately contributes to virus-associated congenital abnormality. Herein, I seek to address the following questions: (i) which host cells are targeted for ZIKV-induced calcifications, and (ii and iii) which and how ZIKV NS3 protease triggers abnormal calcification during infection. This proposal is highly innovative and translational, and potentially shed new insights to ZIKV-induced intracranial calcification that is the most frequent abnormality present in virus-infected babies.",,2025,CLEVELAND CLINIC LERNER COM-CWRU,248999,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2022 +P22206,5R01AI148477-03,Implications of sequential bloodmeals on arbovirus transmission by mosquitoes,"Brackney & Armstrong Abstract: Aedes aegypti is the primary vector for a number of human pathogens, including dengue virus (DENV; Flaviviridae, Flavivirus), Zika virus (ZIKV; Flaviviridae, Flavivirus), chikungunya virus (CHIKV; Togaviridae, Alphavirus) and yellow fever virus (YFV; Flaviviridae, Flavivirus), all of which present a continued threat to human health worldwide. Understanding the endemic and epidemic risk of these arthropod-borne (arbo-) viruses is critical to the success of public health preparedness and intervention. One key entomological parameter informing risk estimates is vector competence (how able a mosquito is to become infected and transmit an arbovirus; VC). Quantifying the competency of local vector populations can help inform the risk that any one pathogen poses to a given community. This is often quantified in the laboratory by exposing populations of local mosquitoes to an infectious bloodmeal and harvesting tissues at set time-points post infection. While informative, this approach often fails to consider the biology and behavior of the vector mosquito. For example, it is known that wild Ae. aegypti mosquitoes will imbibe several bloodmeals over the course of a traditional laboratory-based vector competence study (e.g. bloodmeal every two to three days). To address these shortcomings, we recently began examining the effects that multiple blood feeding episodes have on the competency of Ae. aegypti mosquitoes for ZIKV. Our preliminary findings reveal that providing a second non-infectious bloodmeal to ZIKV infected Ae. aegypti mosquitoes enhances viral escape from the midgut and significantly shortens the duration between mosquito acquisition of ZIKV to transmission. In this application we will examine the effects that multiple bloodfeeding episodes have on arbovirus infection of and transmission by vector mosquitoes. Specifically, we will be 1) testing this phenomenon in other virus-vector pairings, 2) evaluating the role of the midgut basal lamina in mediating the double-feed phenotype and 3) determining if similar processes are mediating the ability of arboviruses to infect ovarian tissue and be transmitted vertically.",,2025,CONNECTICUT AGRICULTURAL EXPERIMENT STA,295756,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Animal and environmental research and research on diseases vectors | Pathogen: natural history, transmission and diagnostics","Vector biology | Pathogen morphology, shedding & natural history",2020 +P22207,5R21AI151475-02,Identification and validation of Zika virus receptor(s) in the midgut lumen of Aedes aegypti,"SUMMARY The central goal of this project is to identify Zika virus (ZIKV) receptor(s), generation ZIKV transmission incompetent transgenic mosquitoes that lack the receptor-encoding gene and identification of novel transmission blocking vaccine candidate(s). Transmission of arthropod-borne viruses (arboviruses) causes widespread and debilitating diseases across the globe. In the absence of effective licensed vaccines or therapeutic treatments of arboviruses, including ZIKV, control at the vector level is the most effective method to ameliorate the burden of these viruses. Before these viruses can be transmitted to humans, they must first infect the mosquito following a blood meal. Thus, investigations to understand ZIKV-mosquito interactions are of critical importance. In this proposal, we will identify specific molecules in the Aedes aegypti mosquito midgut that act as receptors and facilitators for ZIKV binding and establishment of infection. Identified candidate receptors will be validated in vivo by genetic ablation using CRISPR/Cas9 gene editing and subsequent oral challenge with an infectious ZIKV blood meal. Data generated in this study will assist in 1) the development of effective disease control measures, e.g. via the generation of transgenic mosquitoes that lack the receptor-encoding gene and would be incompetent for ZIKV transmission; and 2) identification of ZIKV receptor molecules in the mosquito midgut will provide new insights into the basic biology and molecular mechanisms underpinning the vector competency and mosquito- arboviral pathogen interactions. The proposed experiments are also significant because they provide the groundwork for future experiments that will determine whether the same receptor(s) is used by other arboviruses and other mosquito species.",,2024,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,189370,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22208,5R01AI146049-02,Anchimerically Activatable Anti-Zika/Dengue ProTides,"Arboviruses such as, Dengue (DENV) and Zika (ZIKV), have been associated with several global epidemics. DENV infections can result in a mild fever to potentially fatal dengue shock syndrome, dengue hemorrhagic fever and death, while ZIKV infections can result in congenital microcephaly and the development of autoimmune diseases. Initial clinical manifestation of DENV and ZIKV disease are similar and co-infections have been reported. Most challenging, DENV and ZIKV are known to co-circulate, increasing the probability of co-infections, and thus the potential for severe disease. Consequently, since there is no effective vaccine or form of treatment for either virus, the development of anti-ZIKV and anti-DENV therapeutics is an urgent unmet medical need. Over the past decade prodrugs of nucleotides, referred to as ProTides, have been found to have potent antiviral activity. The anti-hepatitis C virus (HCV) drug sofosbuvir (FDA approved 2013) is the most notable ProTide success, since its use in combination therapy can clear Hepatis C virus infections. Recently, a similar ProTide, remdesivir, has been approved by the FDA, Japan, the European Union an Australia for the treatment of severe SARs-CoV-2 infections by intravenous injection. Carboxyesterase-anhydride-HINT1 (CAH) ProTides, such as sofosbuvir and remdesivir, utilize a four step activation process based on initial esterase hydrolysis, carboxylic acid nucleophilic attack at the phosphorous and release of phenol, followed by mixed anhydride chemical hydrolysis, and finally phosphoramidate hydrolysis by hHINT1. Unfortunately, although they can be dosed intravenously, due to high first pass metabolism, CAH-Protides are limited in their use as oral drugs to viral hepatitis. Furthermore, due to the high carboxyesterase activity of rodent plasma, it has been difficult to carry out pre-clinical studies with rodents and translationally relevant dosages of CAH-ProTides. To address the inherent issues surrounding current ProTide approaches, our group has designed an alternative ProTide approach, we refer to as anchimerically HINT1 activated proTides (AHA-ProTides). Our laboratory has demonstrated that AHA-proTides can be designed that are stable, orally bioavailable, cell permeable and dependent on HINT phosphoramidate hydrolysis. Recently, we have also demonstrated that AHA proTides can be prepared with enhanced potency against DENV and ZIKV. Consequently, we propose to the design and develop anti-DENV and anti-ZIKV AHA ProTides that can serve as advanced lead compounds for the potential treatment of both DENV and ZIKV disease.",,2026,UNIVERSITY OF MINNESOTA,568956,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22209,5R01NS117149-02,Leveraging Zika virus and the immune system to treat glioblastoma,"PROJECT SUMMARY Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2 years. Despite aggressive therapy, most GBMs reappear within 6 months. A major reason for this outcome is because GBM stem cells (GSCs) are resistant to existing therapies. Currently, no treatment consistently kills these highly resistant cells. However, the Zika virus epidemic has provided us with a new approach to eradicate GSCs. ZIKV targets normal stem cells in the developing fetal brain, yet has minimal effects on differentiated neurons or the adult brain. Since GSCs share properties with neural stem cells, we investigated whether the natural honing and lytic activity of ZIKV could be harnessed to target and kill GSCs. We published the first use of ZIKV to kill GSCs. We showed that ZIKV kills GSCs in tumors removed from patients, with minimal impact on non-GSC tumor cells, called differentiated GBM cells. Importantly, normal human brain cells were not affected by ZIKV. After intracranial treatment with ZIKV, mice harboring gliomas survived more than twice as long as untreated mice and, in some cases, treated mice were long-term survivors. In addition to the resistance of GBM stem cell to chemoradiation, GBM is the hallmark example of an immunotherapy-resistant tumor. Importantly, we found that in vivo, ZIKV treatment reduces tumor size and extends survival beyond that expected for only anti-GSC effects. This suggested that ZIKV killing of GSCs may trigger an immune response against the remainder of the tumor. In more recent studies, we have found that CD8+ T cells are required for the efficacy of ZIKV as an oncolytic therapy in vivo. Our central hypothesis is that ZIKV elicits an anti-tumor immune response that could be made even more effective by combining it with existing immunotherapies. Aim 1 will determine how CD8+ T cells promote tumor clearance after ZIKV and Aim 2 will determine whether ZIKV can be combined with immunotherapy or standard-of-care for GBM to improve outcomes. Our long-term goal is to develop a new treatment for GBM by leveraging the immune system response to ZIKV.",,2025,WASHINGTON UNIVERSITY,392641,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2020 +P22210,5F31AI154695-02,Effect of an Fc Gamma Receptor Polymorphism on Antibody-Dependent Enhancement of Zika Virus Infection,"PROJECT SUMMARY Antibody-dependent enhancement (ADE) is a phenomenon by which antibodies raised in response to a primary infection cross-react to a similar pathogen during a subsequent infection, resulting in increased viral load and severity of disease. ADE of Zika virus (ZIKV) infection by preexisting DENV antibodies has been hypothesized to play a role in the severe adverse pregnancy outcomes observed following congenital ZIKV infection. ADE is mediated by interactions between virus-bound IgG antibodies and Fc gamma receptors (FcRs) on host cells. In humans, a nonsynonymous single nucleotide polymorphism (SNP) in FCGR2A, rs1801274, results in an amino acid change at site 131 from arginine (Arg131) to histidine (His131) in the IgG-binding region of FcRIIA. Previous work in vitro has shown that cells expressing the His131 receptor variant bind human IgG1 and IgG2 with significantly higher affinity than those expressing the Arg131 receptor variant. We hypothesize that individuals homozygous for the high affinity His131 allele will be at greater risk for ADE of viral infection than individuals homozygous for the low affinity Arg131 allele. In this application, we will assess the effect of this SNP on ADE of ZIKV using cell lines derived from K562 cells that are homozygous for the Arg131 or His131 allele and primary human monocytes that will be stratified by genotype (Aim 1). We have also generated IgG subclass switch variants of a flavivirus-reactive monoclonal antibody that we will use to assess the role of each IgG subclass in mediating ADE of ZIKV through the different FcRIIA variants using His131 and Arg131 homozygous K562 cell lines, primary human monocytes, and Hofbauer cells isolated from full term human placentas (Aim 2). A comprehensive understanding of host genetic factors that affect susceptibility to ADE, including those described in this proposal, may help to identify populations at increased risk of developing severe disease as a result of ZIKV infection, particularly among pregnant women. The proposed project provides an excellent opportunity for training that encapsulates traditional virology and immunology techniques, professional development, and mentorship that will support the applicant’s growth as an independent academic scientist.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,45152,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2021 +P22211,5R21AI157147-02,Three-dimensional human epithelial cultures as a model for evaluation of flavivirus-host interactions driving infection in the skin,"PROJECT SUMMARY Zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV) all cause severe human disease as a result of their widespread mosquito-borne transmission. While these flaviviruses share a common primary site of infection in the dermis, they disseminate to varying secondary sites of infection with highly divergent clinical outcomes. We propose that discrepancies in early virus-host interactions among ZIKV, DENV, and WNV are responsible for these differences in disease; however, there is a gap in our knowledge of the molecular mechanisms responsible. Elucidation of distinct virus-host interactions occurring at the initial infection site is thus key to understanding how these viruses establish productive infections in the skin and elsewhere. The proposed research will establish organotypic epithelial cultures as a genetically tractable and immunocompetent 3D human skin model of flavivirus infection, to be used for virus-host interaction studies. We will expand on the current model commonly used to study DNA viruses, typically comprised solely of human fibroblasts and keratinocytes, with the addition of human skin-resident dendritic cells and macrophages, to accurately recreate natural flavivirus infection in the skin. Additionally, we will incorporate mosquito saliva, which includes immunomodulatory and anti-inflammatory proteins, into the virus inoculum to further recapitulate the molecular events occurring at the primary site of flavivirus infection. We will determine individual infection conditions for ZIKV, DENV, and WNV, and evaluate cell tropism and host responses with each virus. Once established, we will employ this 3D human skin model to evaluate the role of the host ribonuclease L (RNase L) protein during ZIKV infection in the skin, which will validate this system for flavivirus-host interaction studies. While antiviral RNase L activity is well described, we have recently discovered proviral RNase L activity during ZIKV infection. In contrast, we observed canonical antiviral RNase L activity during DENV and WNV infections. These studies were performed in 2D monolayer culture systems with immortalized cell lines, therefore we will use our 3D skin model containing primary cells to test the hypothesis that RNase L plays a role in ZIKV cell tropism and spread in the skin in a more relevant system. We will use CRISPR-Cas9 gene editing to delete RNase L from the different skin cells comprising epithelial cultures, and subsequently generate RNase L-deficient skin cultures for infections with ZIKV, DENV, or WNV. We will assess effects of RNase L deletion on infection and spread of the different flaviviruses in the skin, as well as how host responses are impacted. The proposed studies will characterize the role of RNase L as an important host factor repurposed by ZIKV during infection in the skin. Furthermore, this project will establish organotypic epithelial cultures as an exciting new human model amenable to gene editing which will facilitate inquiries of arbovirus-host interactions and host responses at the common primary infection site of the skin.",,2024,UNIVERSITY OF PENNSYLVANIA,243750,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease models | Disease pathogenesis",2021 +P22212,5R01AI155735-02,Multiplexed Detection of Mosquito-Borne Viruses at the Point-of-Care,"Project Summary Dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), and Mayaro virus (MAYV) are all mosquito-borne RNA viruses. They are public health concerns because (1) DENV and CHIKV cause hundreds of millions of infections each year, with significant burdens in affected areas, (2) the outbreak of ZIKV in Brazil in 2015/2016 caused anxieties to general population due to its association with microcephaly of newborns, and (3) MAYV emerged in Central and Southern America recently and has the potential for epidemic spread. Because these virus infections have virtually identical clinical presentation and they often circulate concurrently, it is important to have a point-of-care (POC) testing platform to accurately identify virus infection for clinical management of patients, including different complications from these viruses. According to the Centers for Disease Control and Prevention (CDC), the current methods authorized for assessing DENV, ZIKV, and CHIKV infections include reverse transcription polymerase chain reaction (RT- PCR) assay and enzyme-linked immunosorbent assay (ELISA). However, these assays are carried out in laboratories, not at POC in a clinic or in an infected field. It is also important to note that virus infection can cause asymptomatic infections, up to 80% of ZIKV patients, 50% of DENV patients, and 28% of CHIKV patients, respectively. As a result, POC testing in the field will be more valuable for screening asymptomatic patients and monitoring possible virus transmission than a laboratory test because only symptomatic patients go to hospitals or clinics for seeking medical help or to be screened. To address the need, we propose to develop a POC diagnostic platform called Valve-enabled Lysis, paper- based RNA Enrichment, and RNA Amplification Devices (VLEAD). VLEAD will integrate sample preparationâ€Â"" including virus lysis and RNA enrichmentâ€Â""with nucleic acid amplification for simultaneous detection of these viruses. To achieve the goal, we aim to (1) develop multiplexed VLEAD for simultaneous detection of ZIKV, DENV, CHIKV and MAYV; (2) optimize VLEAD using various samples and compare the suitability of the device for urine, saliva and blood samples; and (3) validate VLEAD using clinical samples and compare VLEAD with the benchmark methods including conventional RT-PCR. The significance of the research lies in the following aspects. First, these mosquito-borne RNA viruses are a public health concern. An accurate and sample-to-answer virus detection platform at POC will be useful for clinical care and patient management. Second, a large percentage of these virus infections are asymptomatic, thus a non-invasive POC platform would be very beneficial for screening the general population in the infected area and monitoring virus transmission. Third, the VLEAD platform can be adapted for detecting other pathogens of interest, with a potential to have more societal impacts.",,2025,UNIVERSITY OF FLORIDA,371905,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Post acute and long term health consequences,2021 +P22213,5R21AI156575-02,Global effects of flavivirus sfRNA on translation determined by ribosome profiling,"Flaviviruses include many serious pathogens such as Zika, dengue, West Nile, and yellow fever viruses. In infected cells these viruses produce abundant, noncoding, short flavivirus RNAs (sfRNAs) that comprise most of the ~500 nucleotide 3’ untranslated region of the viral genome. These novel viral RNAs have been shown recently to interact with numerous host proteins and inhibit translation (protein synthesis) of certain genes of the innate immune system. Thus, virus strains that produce high levels of sfRNA are more pathogenic, and mutants that produce no sfRNA are so mild as to be promising vaccine candidates. However, a picture of how sfRNA globally affects translation of cellular mRNAs is lacking. The Zika virus (ZIKV) epidemic of 2014-16 resulted in frighteningly frequent cases of microcephaly and other developmental and neurological disorders caused by exposure to ZIKV in utero. In addition to inhibiting the immune response, ZIKV sfRNA inhibits Fragile X Mental Retardation Protein (FMRP), a key translational regulator of neurological development. Thus, this knowledge of the global effects of ZIKV sfRNA on host translation could contribute to future research on understanding how this virus manipulates the host and causes disease. Method: We will employ the transformative method of ribosome profiling (RiboSeq) to sample the level of translation across the entire population of mRNAs in the cell in order to identify genes that are translationally up- or down-regulated in the presence of sfRNA, either alone, or in the context of replicating ZIKV. RiboSeq - a modification of high-throughput mRNA sequencing (RNAseq) - reveals only the fragments of mRNAs that are protected by translating ribosomes. The number of reads of ribosome-protected fragments from a given mRNA is proportional to how actively that mRNA is translated. This highly informative method has been applied only sparingly to flaviviruses and, to our knowledge, never to determine specifically the effects of sfRNA, a known translational regulator. We will also develop new statistical methods to improve on current imperfect approaches for calculating significance of changes in translational efficiency of mRNAs in response to a treatment. Finally, we will use a variety of bioinformatics tools to identify common structural features of mRNAs whose translation efficiencies are similarly affected by sfRNA. Expected Outcomes. Identification of genes whose translation is affected by sfRNAs will reveal potential genes and genetic pathways that facilitate - or defend against â€Â"" ZIKV infection. These can be the focus of future studies by us and others to determine their role and regulation in virus infection, the immune response, or possibly neurodevelopmental disorders. Moreover, these results may reveal new ways of regulating translation. This research can benefit human health by informing rational design of vaccines or antivirals targeting ZIKV and other flaviviruses, and by providing better understanding of control of protein synthesis by RNA.",,2024,IOWA STATE UNIVERSITY,216354,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22214,5U24AI152170-03,"Multiplex serological assays to support arbovirus diagnosis, surveillance and vaccines","Abstract At a global level, ongoing ecological, environmental and demographic changes favor the survival and expansion of several mosquito and tick species that transmit arboviruses. Aedes mosquito species that thrive in urban environments created by humans are responsible for epidemics of several flaviviruses [dengue virus (DENV) serotypes 1, 2, 3, 4; Zika virus (ZIKV); yellow fever virus (YFV)] and alphaviruses [chikungunya virus (CHIKV) and Mayaro virus (MAYV)]. Laboratory-based diagnosis and surveillance for arboviruses is difficult because most infected individuals are asymptomatic or develop a mild undifferentiated febrile illness. Serological assays have been developed for the detection of recent or past arboviral infections, but the utility of these assays is severely limited by antibody cross reactivity between related viruses. For example, when ZIKV emerged in many regions of the Americas where greater than 80% of the population was dengue-immune, with current serological assays, it was difficult, if not impossible, to identify infected individuals or monitor the spread of ZIKV at a population level, and likewise to now detect new DENV infections in areas that experienced intense ZIKV epidemics. Our studies over the past 10 years demonstrate that people exposed to flavivirus infections reliably develop antibodies to epitopes that are unique to each flavivirus as well as cross-reactive antibodies. Using our discoveries about the location of immunodominant virus type-specific epitopes, we have produced novel recombinant antigens and demonstrated their utility for the type-specific diagnosis of arboviruses. Under Specific Aim 1 of this proposal, we will build on these discoveries to develop a sample-sparing, microsphere bead-based multiplex assay for the type-specific and sensitive detection of recent or past arbovirus infections. Our initial studies will focus on 8 arboviruses transmitted by Aedes aegypti and Aedes albopictus mosquitos because these viruses share a similar ecology and co-circulate in the same human populations. At a second stage, we will expand the coverage of the assay to detect infections with other arboviruses transmitted by other mosquito species and ticks. Several tetravalent DENV and ZIKV vaccines are currently being evaluated in human clinical trials. While vaccine developers have relied on neutralizing antibodies as a correlate of protection, recent results from clinical trials demonstrate that neutralizing antibodies alone are a poor correlate of vaccine safety and efficacy. We have identified flavivirus type- and epitope-specific antibody responses that are better predictors than neutralizing antibodies of vaccine safety and efficacy. Under Specific aim 2 of this proposal, we will develop a sample-sparing microsphere-based assay for the detection of epitope-specific vaccine-induced antibody responses that are correlated with protective immunity to each of the DENV serotypes and ZIKV. The technological advances and products from this proposal will enhance our ability to efficiently monitor arbovirus infections at the individual and population levels and also support the development of arbovirus vaccines.",,2025,UNIV OF NORTH CAROLINA CHAPEL HILL,413630,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +P22217,1R56AI167980-01,Optimization of low-threshold Cas9-based gene drive systems to introduce Zika virus resistance in Aedes aegypti,"Project Summary Aedes aegypti is the principal vector of arthropod-borne viruses (arboviruses) affecting human health in the tropics, such as Zika, chikungunya, and dengue viruses. Zika virus (ZIKV) caused the most recent major epidemic arbovirus outbreak in the New World Hemisphere. As a wide-spread, peridomestic vector in tropical regions, Ae. aegypti has become ever more difficult to control. Many populations have become resistant to commonly used insecticides increasing the need for alternative control strategies. One such alternative is the use of genetically-modified virus-resistant mosquitoes to disrupt the arboviral disease cycle, however this approach requires a mechanism to spread and fix the transgene within a population. Newly developed gene drive (GD) systems are capable of this, as they bias the inheritance of genes in a super-Mendelian fashion. GD systems can be broadly classified into population suppression and population replacement, with the former resulting in population collapse, and the latter resulting in the fixation of a transgene in a population. Population replacement is a concept still under development, and requires two genetic components: a strong antiviral effector, and a robust GD system. Due to the GD-linked spread of the anti-viral effector gene, a targeted virus- susceptible wild population would be converted into a virus-resistant one. Recently, we developed an anti-viral effector gene that specifically targets ZIKV by triggering the mosquito’s RNAi pathway. Here, we seek to combine the anti-ZIKV effector with low-threshold homing GDs based on Cas9, which so far, have not been developed for Ae. aegypti. These GDs rely on homology dependent DNA repair in the germline, however the expression of Cas9 outside of the germline can lead to GD-resistant indels. GD-blocking indels can be mitigated through the optimization of Cas9 expression, or through the use of novel GD architectures capable of removing such indels when they arise. In four Specific Aims (SA), we propose to develop for Ae. aegypti reliable low-threshold GD systems which are linked to an anti-ZIKV effector: 1) Identify the optimal promoter for Cas9 expression in single-component GD at different genomic loci; 2) Design and generate novel GD (ClvR, HomeR) variants that remove indels; 3) Develop germline::Cas9 gene fusions for a dual-GD systems to allow for the independent drive of the anti-ZIKV effector; 4) Monitor the activity of the optimized GD systems (SA.1-3) in wild-type like mosquitoes via non-overlapping small cage studies over multiple generations. The four SA of this application will identify a GD design for Ae. aegypti that will allow for the robust introduction of new traits, such as resistance to ZIKV, into wild mosquito populations.",,2024,UNIVERSITY OF MISSOURI-COLUMBIA,537024,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Vector biology",2022 +P22218,5R01AI155983-02,Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and -experienced Individuals,"Project Title: Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and - experienced Individuals Project Summary Zika virus (ZIKV) is a member of the flavivirus genus that recently precipitated widespread cases of neurological pathology and congenital neurologic defects. In response, a multilateral coalition of investigators designed and developed multiple vaccine candidates that elicited potent ZIKV-neutralizing antibodies, which were shown to correlate with disease protection in animal models. Despite these advances, it remains unclear how the ZIKV immunization antibody response is shaped in humans with and without prior exposure to other flaviviruses, such as dengue virus (DENV), Japanese encephalitis (JEV) or yellow fever virus (YFV); particularly as these viruses all have significant epidemiologic overlap with ZIKV. Our long-term goal is to understand the underlying humoral mechanisms generated by flavivirus vaccination, which can provide long-term protection in flavivirus-naïve and/or -experienced populations. Such information would guide vaccination strategies in flavivirus-endemic areas or among flavivirus-naïve individuals traveling to endemic areas. The overall objective of this proposed research is to evaluate the specificity and function of the B cell repertoire elicited by ZIKV vaccination in flavivirus- naïve and -experienced individuals. To achieve these goals, this research will utilize leading-edge technologies to sequence B cell receptors (BCRs) from flavivirus-specific, single B cells using RNAseq and Next Generation Sequencing (NGS). BCRs will be compared between Zika vaccinated individuals, and to previously published monoclonal antibodies, to determine the prevalence of B cell lineages, gene assignment, degree of somatic hypermutation (SHM), and lengths of heavy chain complementary-determining region 3 (HCDR3). Common B cell lineages will be expressed as monoclonal antibodies and evaluated for their specificity, function, structural, and ability to protect against flavivirus challenges in mouse models. A total of 40 samples will be evaluated from individuals representing 5 groups in 3 different Phase I Zika vaccine clinical trials: a) Flavivirus-naïve individuals who were vaccinated using a Zika purified inactivated whole virus vaccine (ZPIV) b) Flavivirus-naïve individuals who were vaccinated with an adeno-vectored Zika M-E (Ad26.ZIKV.M-Env) c) Individuals living in Puerto Rico with prior dengue infection who were ZPIV vaccinated d) JEV (IXIAROÃ'®) vaccinated individuals who were ZPIV vaccinated and e) YFV (YV-VAXÃ'®) vaccinated individuals who were ZPIV vaccinated. Flavivirus-naïve, Zika vaccinated individuals (Groups a-b) will be explored in Aim 1 and Flavivirus-experienced individuals, either by prior infection (Group c) or by prior vaccination (Groups d-e), will be explored in Aim 2. Aim 3 will examine a late timepoint (6 months) following the last ZPIV vaccination to determine the longevity of the circulating B cell lineages characterized in Aims 1 and 2. Evaluating prevalent B cell lineages responding to Zika vaccination will reveal the specificity, function and durability of the humoral response among individuals living in different regions. These studies will provide insights into the potency and durability of ZIKV vaccine responses in both flavivirus- naïve and -experienced individuals and may translate into vaccine strategies that yield long-lived protection.",,2026,HENRY M. JACKSON FDN FOR THE ADV MIL/MED,859058,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Characterisation of vaccine-induced immunity",2021 +P22219,5R01AI153434-02,Flavivirus immunity in endemic and non-endemic human cohorts,"PROJECT SUMMARY The global spread of the arthropod borne flaviviruses dengue (DENV1-4) and Zika (ZIKV) viruses are major global public health challenges. World health organizations are calling for scientific communities to respond to this emerging threat with vaccines, therapeutics and diagnostics. However, existing gaps in fundamental knowledge about DENV and ZIKV immunity, specifically how type-specific immunity to each serotype develops and is sustained, makes rational vaccine development particularly difficult. The dominant immunity model comes from human challenge studies on DENV (1910’s-1940’s) and posits that first infection induces neutralizing antibodies that provide life-long sterilizing immunity to repeat infections by the same (homotypic) serotype virus, and this model has been extended to ZIKV without rigorous evaluation. However, recent studies from DENV endemic regions provide evidence of homotypic re-infection and natural immune boosting over time and our preliminary data from a non-endemic, Portland, Oregon resident DENV and ZIKV immune cohort show type- specific Abs decay â€Â"" lose both potency and breadth - over time, calling into question sterilizing immunity and leading us to hypothesize that natural flavivirus (ZIKV and DENV) protective immunity is context dependent: in endemic transmission settings intermittent asymptomatic boosting maintains potency and breadth of virus specific immunity and in non-endemic or very low transmission settings potency and breadth of flavivirus immunity significantly wanes. To test this hypothesis, we propose to prospectively characterize and compare DENV and ZIKV immunity in a regularly re-exposed endemic cohort in Ponce, Puerto Rico with immunity in an un-boosted, non-endemic cohort of DENV immunes in Portland. This is a controversial and novel hypothesis that will call for substantial supporting evidence, hence we will compare and contrast three highly relevant and related markers of boosting between the two cohorts: The potency and breadth of neutralizing serum DENV and ZIKV specific Abs (Aim 1), the frequency of and potency of DENV and ZIKV non-structural protein 1 (NS1) specific antibodies (Aim 2), and the frequency and specificity of DENV and ZIKV specific memory B-cells (MBCs) (Aim 3). We expect to find that Abs and MBCs decline at a significantly greater rate in individuals from the non- endemic setting compared to the endemic setting supporting the hypothesis that boosting plays a critical role in natural immunity for these viruses, with implications for future vaccine development. Because MBCs are functionally linked to Abs, quantifying virus specific MBCs tests a mechanistic connection between repeat infection and Ab titer boosting. Our proposed work will comprehensively assess the role transmission context plays in flavivirus immunity using two highly relevant and mechanistically linked determinants (Ab and MBC). Irrespective of specific results, the knowledge obtained from the proposed work will be essential to DENV vaccine development and mechanistic understanding of flavivirus Ab mediated immunity.",,2026,OREGON HEALTH & SCIENCE UNIVERSITY,383984,Human Populations,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22220,5R01AI153419-02,Mechanistic Insights into flavivirus NS5-mediated STAT2 Suppression,"The family of flavivirus consists of over 90 vector-borne, single-stranded RNA-containing viruses, including Dengue virus (DENV) and Zika virus (ZIKV), which cause major epidemics among humans and pose a serious threat to global public health. No vaccines or antivirals exist to prevent or treat infections caused by DENV, ZIKV, and some other flaviviruses. To establish infection, flaviviruses need to overcome the antiviral state induced by type 1 interferon (IFN-1), the first line of host defense. In this regard, flaviviruses have encoded several antagonists to suppress IFN responses. For example, the nonstructural NS5 proteins of DENV, ZIKV, and some other flaviviruses have been shown to be potent suppressor of IFN signaling, targeting different steps of the IFN signaling pathway. Like DENV, ZIKV NS5 protein bind human signal transducer and activator of transcription 2 (hSTAT2) protein and trigger its proteasomal degradation, albeit using different downstream mechanisms. To elucidate the mechanistic basis of flavivirus NS5-mediated hSTAT2 suppression, we propose to provide structural insight into the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 complexes, which, in turn, will guide interrogation of the consequence(s) of the flavivirus NS5-hSTAT2 interactions in proteasome-mediated degradation of hSTAT2 and suppression of IFN signaling. Toward this goal, we will use structural, biochemical, molecular, cellular and virology approaches to investigate the structural basis of the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 interactions and their functional consequence. In Aim 1, we will establish the structural basis of the ZIKV-hSTAT2 interaction by using X-ray crystallography and cryo-electron microscopy and validate our observations with mutational and in vitro pull-down analyses. In Aim 2, we will examine the ZIKV NS5-hSTAT2 interaction at a cellular level and investigate the functional consequence of the ZIKV NS5-hSTAT2 interaction through evaluation of the mutational effects of ZIKV NS5 on hSTAT2 degradation, IFN response and viral infection. The results of these studies will provide critical structural and functional insights into the virus- and species-specific ZIKV NS5-hSTAT2 interaction, thereby establishing a mechanistic link between flavivirus NS5 proteins, hSTAT2 degradation, suppression of the IFN response and viral infection. Results from the proposed studies will ultimately benefit development of novel antivirals and live vaccines against flaviviruses infection.",,2026,UNIVERSITY OF CALIFORNIA RIVERSIDE,388750,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22221,5R01AI145918-03,Trade-offs between Arbovirus Transmission and Clearance in Native and Novel Hosts,"Research Summary The recent introduction of Zika virus (ZIKV) into the New World sparked concern that the virus would emerge into a sylvatic cycle in American non-human primates (NHPs) and mosquitoes. The ability of a pathogen to emerge into a novel host species is determined, in part, by the virulence of that pathogen in the novel species. Current theory on the evolution of virulence rests on the premise that pathogen fitness is maximized by optimizing the trade-off between instantaneous pathogen transmissibility and duration of infection. While most theoretical studies of virulence evolution have focused on the trade-off between transmission and host mortality, the majority of pathogens do not kill their hosts. Instead, most infections are curtailed by the host immune response, leading to a transmission-clearance trade-off. Studies of the transmission-clearance trade-off are scarce, but we have previously found that, across multiple studies in the literature, there is an inverse relationship between peak virus titer and duration of infection when arthropod-borne viruses are experimentally inoculated into natural hosts. Moreover, we have leveraged these data to model alternate transmission strategies, namely a “tortoise” strategy of low magnitude, long duration viremia and a “hare” strategy of short duration, high magnitude viremia and found that arboviruses that adopted a tortoise strategy had higher rates of persistence in both host and vector populations. Nonetheless current understanding of transmission-clearance trade-offs in arboviruses is rudimentary, and integrated experimental and modeling studies of arbovirus trade-offs in ecologically-relevant host and vector species are needed to appropriately assess the risk of establishment of sylvatic cycles in new areas and the subsequent risk of emergence from such cycles. To this end, we will quantify dynamics of ZIKV and dengue virus (DENV) infection, immune response, and transmission in native NHP hosts (cynomolgus macaques) as well as novel, American NHPs (squirrel monkeys) to identify transmission-clearance trade-offs, and we will build models to predict the impact of such trade-offs on virus persistence in host populations. DENV is chosen as a counterpoint to ZIKV because, despite circulating in humans in the Americas for centuries, it has not yet established an American sylvatic cycle [17]. We will test four specific hypotheses: (i) In native hosts and novel hosts, sylvatic arboviruses experience a transmission-clearance trade-off; (ii) In native and novel hosts, the innate immune response shapes the transmission-clearance trade-off; (iii) Sylvatic arboviruses experience different transmission-clearance trade-offs in native hosts and novel hosts, resulting in less transmission from novel hosts; (iv) DENV and ZIKV lineages from human-endemic transmission cycles experience different transmission-clearance trade-offs than their sylvatic ancestors in native NHP hosts, but similar patterns in novel NHP hosts.",,2024,NEW MEXICO STATE UNIVERSITY LAS CRUCES,771464,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models | Animal source and routes of transmission",2020 +P22222,5R01AI149502-03,Multiplex Serodiagnostic Assays for Pathogenic Arboviruses in Brazil,"Abstract A critical need exists for highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses in geographic regions, such as Brazil, where multiple flaviviruses including Zika virus (ZIKV), four serotypes of dengue virus (DENV1-4), West Nile virus (WNV), and yellow fever (YFV), as well as chikungunya virus (CHIKV), Mayaro virus (MAYV) (both alphaviruses) and Oropouche virus (OROV) (a bunyavirus), are endemic. However, cross-reactivity of antibodies against different flaviviruses present major challenges, such that even neutralization tests cannot confirm a specific flavivirus infection among individuals who have experienced previous flavivirus infections. The objective of the proposed research is to develop highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses. The central hypothesis is that a combination of fusion loop (FL)-mutated VLPs and nonstructural protein 1 (NS1) proteins of different flaviviruses and recombinant proteins and VLPs of CHIKV, MAYV and OROV in multiplex formats can distinguish different arbovirus infections. The first Aim is to develop and validate multiplex IgG and IgM microsphere immunoassays (MIAs) based on recombinant proteins to distinguish arbovirus infections. We will employ recombinant NS1 proteins of 7 flaviviruses, envelope (E) 2 protein and nucleocapsid (N) protein of CHIKV, MAYV and OROV for multiplex IgG and IgM MIAs using Luminex 200 and test with 15 panels of convalescent-phase serum/plasma from individuals with confirmed arbovirus infections. The second Aim is to develop and validate multiplex IgG and IgM MIAs based on VLPs to distinguish arbovirus infections. We will use purified and FL-mutated VLPs of 7 flaviviruses and VLPs of CHIKV, MAYV and OROV, and test with 15 panels of serum/plasma as in Aim 1. The third Aim is to compare the multiplex IgM MIAs and IgG MIAs with currently available serodiagnostic assays to determine arbovirus seroprevalence in Bahia, a northeastern state with multiple arbovirus transmissions in Brazil. For serodiagnosis, we will test serum samples from patients with acute febrile illness and their follow-up at outpatient clinics of 4 study sites (Salvador, Feira de Santana, Itabuna and Campo Formoso) in Bahia. For seroprevalence study, we will enroll and test household members at communities of the 4 study sites. The proposed study is innovative as it employs two promising antigens (NS1 protein and FL-mutated VLPs) to overcome flavivirus cross-reactivity for seven flaviviruses, as opposed to traditional E protein-based tests, plus CHIKV, MAYV and OROV in two multiplex formats to discriminate arbovirus infections in Brazil. It would contribute to a detailed understanding of the epidemiology of 10 arbovirus infections in Bahia. The successful employment of the multiplex platforms can serve as a new paradigm for serodiagnosis and serosurveillance in countries where multiple arboviruses co-circulate. Most importantly, this research will facilitate the implementation of arbovirus vaccines, in particular ZIKV, DENV and CHIKV vaccines in endemic regions.",,2024,UNIVERSITY OF HAWAII AT MANOA,156458,Human Populations | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical,Not applicable,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +P22223,5R01AI158194-02,Structure-based design of broad flavivirus immunogens,"SUMMARY Dengue virus is a mosquito-transmitted flavivirus that causes an estimated 390 million human infections each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions. Primary infection by a single DENV serotype results in febrile illness and subsequent durable immunity to that serotype. Secondary infections by heterotypic serotypes can lead to severe shock syndrome and death. Severe Dengue disease is caused in part by cross-reactive antibodies elicited during primary infection that can bind heterologous DENV serotypes but cannot neutralize them. Instead, these non-neutralizing antibodies facilitate entry and infection in Fcγ receptor-positive cells, thus causing ""antibody-dependent enhancement"" (ADE) of infection. While a live-attenuated four-component chimeric vaccine was recently deployed in 19 countries and Europe, this vaccine does not protect naïve individuals against symptomatic or severe infection, and may even exacerbate disease in some cases. Furthermore, the global emergence of Zika virus (ZIKV), and the potential for ADE between DENV and ZIKV, raises concerns for vaccine strategies containing most or all epitopes in the E glycoprotein. Nonetheless, the isolation and characterization of protective and, in some cases, broadly-neutralizing antibodies indicates that certain epitopes within the E glycoprotein may have the capacity to elicit broadly protective responses. Here, we utilize innovative protein engineering approaches to develop “immune-focused” antigens as potential vaccine candidates, in which epitopes that induce non-neutralizing antibodies are masked by engineered mutations or glycosylation. Our hypothesis is that masking of these unfavorable epitopes will skew the immune response toward a stronger neutralizing, protective, and broad response. Aims 1 and 2 focus on critical epitopes in DENV and ZIKV E domain III (EDIII), and Aim 3 explores glycan masking of the ZIKV E prefusion dimer to immune focus on the E-dimer epitope (EDE). EDIII is attractive for subunit vaccine design because it is the target of potently neutralizing and protective antibodies for both DENV and ZIKV. However, immunization with wild-type EDIII protein results in induction of both neutralizing and non-neutralizing antibodies that engage a variety of epitopes. We have used phage display to mask unproductive epitopes of DENV and ZIKV EDIIIs by mutation, while maintaining neutralizing epitopes. These “resurfaced EDIIIs” (rsDIIIs) will be conjugated to protein nanoparticles and their capacity to induce neutralizing and protective antibody response in mice evaluated. To immune focus the prefusion E dimer on the EDE, we have developed a mammalian display system that allows for rapid evaluation of E dimer constructs for binding to EDE mAbs. We will utilize this system to screen variants with multiple engineered glycosylation sites that mask the surface outside of the EDE. The most promising candidates will be tested for their capacity to induce EDE-like mAbs in mice. This work will provide a proof-of-concept for novel subunit vaccine candidates against DENV, ZIKV, and possibly other flaviviruses of global concern.",,2026,ALBERT EINSTEIN COLLEGE OF MEDICINE,738795,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22224,1U19AI171421-01,"Targeting viral envelopes with antiviral peptides and peptoids and degraders, and surface proteins with small molecules","ABSTRACT. Our overall objective is to develop a new class of direct acting-antivirals (DAAs) that can specifically target viral envelopes but not host cell membranes using our novel amphipathic, α-helical (AH) Lipid Envelope Antiviral Disruption (LEAD) peptides and peptoids (sequence-specific N-substituted glycine oligomers). Therapeutics that can specifically target enveloped viruses have the potential to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a wide variety of RNA viruses of pandemic potential. One promising target is the lipid membrane coating that surrounds enveloped viruses, as membrane disruption can abrogate viral infectivity. This team’s investigators have developed a new class of AH peptides, and another new type of self-assembling amphipathic peptoids, that selectively form pores in high-curvature membranes such as membrane-enveloped virus particles (<160 nm diameter) but do not form pores in low-curvature membranes such as those of mammalian cells. Once a critical density of pores forms in the viral membrane, pore-induced membrane lysis occurs, leading to loss of viral infectivity. We have also showed that incorporating D-amino acids (instead of natural L-amino acids) into LEAD peptides can enhance their in vivo stability. Excitingly, our preliminary data to date showed that one LEAD peptide (AH-D) has potent antiviral activity against a wide range of enveloped viruses including Zika virus (ZIKV), Dengue virus (DENV), Chikungunya virus (CHIKV), Yellow Fever virus (YFV), Japanese encephalitis virus (JEV), and SARS-CoV-2 without cellular toxicity in vitro. Even more excitingly, when administered in vivo, AH-D peptide can protect mice against lethal ZIKV infections as well as block DENV viremia. We have also recently developed novel antiviral peptoids that can similarly target viral envelopes selectively, with potent anti-SARS-CoV-2 activity. Finally, subcutaneous administration of a LEAD peptide had reasonably comparable exposure but with a longer half-life than when administered intravenously. We now seek to advance the development of a promising lead molecule by: 1) further characterizing the biophysical properties of LEAD peptides and peptoids responsible for their antiviral activity against enveloped viruses; 2) optimizing in vivo pharmacokinetics (PK) of LEAD peptides and peptoids for subcutaneous and inhalation delivery (by collaborating with Project 2) suitable for outpatient administration; 3) evaluating antiviral efficacy of the optimized LEAD peptides and peptoids in mouse models of DENV, ZIKV, and SARS-CoV-2; and 4) nominating a top-performing LEAD peptide/peptoid for IND-enabling studies by collaborating with Project 6 on mechanisms of potential resistance to our top performing molecules, conducting synergy studies with other available DAAs including ones developed in SyneRx, and beginning initial assessments of in vitro ADME and in vivo non-GLP rat toxicity. Successful completion of our aims will yield an exciting novel class of DAAs that can specifically target viral envelopes for use alone, or in combination with other DAAs, to combat SARS-CoV-2 and other infections caused by membrane-enveloped viruses with pandemic potential.",,2025,STANFORD UNIVERSITY,2909919,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22225,5U01AI148069-03,Quanitifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases,"Project Summary/Abstract Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes- borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections. Novel vector control approaches and intervention delivery strategies to contain ABVs are urgently needed. Targeted indoor residual spraying (TIRS, applying residual insecticides on Aedes aegypti resting sites such as exposed low walls [<1.5m], under furniture, and on dark surfaces) is a rational vector control approach that exploits Ae. aegypti resting behavior to focalize insecticide applications with no loss in residual efficacy. Recently published systematic reviews have identified TIRS as a very promising approach for ABD prevention, but highlighted the limited evidence-base for this intervention due to the absence of efficacy estimates from randomized controlled trials with epidemiological endpoints performed in endemic settings. In response to such critical need, we will pursue a two-arm, parallel, unblinded cluster randomized trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory- confirmed (virologically or serologically) ABV clinical disease (e.g., dengue, Zika or chikungunya) (primary endpoint). Secondary endpoints will include: a) Laboratory-confirmed (serologically) DENV, CHIKV or ZIKV seroconversion in children aged 2-15 at enrollment; b) Ae. aegypti mosquito infection rates with DENV, CHIKV or ZIKV; c) Ae. aegypti indoor entomological indices. The trial will be conducted in the city of Merida (Yucatan State, Mexico, population ~1million), where we will prospectively follow a population of 4,600 children 2-15 years at enrollment, distributed in 50 clusters of 5x5 city blocks each (~92 children per cluster), randomly allocated to receive either TIRS treatment (n=25) or not (n=25). Trained personnel from the Federal Ministry of Health will perform TIRS in all houses from the treatment clusters ~1-2 months prior to the beginning of the peak ABV transmission season. Active monitoring for symptomatic ABD infections will be performed by field nurses and doctors through weekly household visits and enhanced surveillance (phone calls, monitoring of suspected cases to Merida’s hospital/clinic system), whereas annual sero-surveys will be performed after each transmission season. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to guide insecticide applications; change to preemptive control (pre- ABV transmission season rather than in response to symptomatic cases); the use of insecticide formulations to which Ae. Aegypti is susceptible.",,2025,EMORY UNIVERSITY,1356994,Human Populations | Disease Vectors,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,"Vector control strategies | Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures",2020 +P22226,7R01HD097608-06,IL-1B regulation of Zika-Mediated adverse perinatal outcomes,"SUMMARY Zika virus (ZIKV) infection of pregnant females results in congenital infection of offspring and long-term developmental birth defects. Using an immunocompetent mouse model that we developed (published in Nature Communications), we have shown that intrauterine infection with either African, American, or Asian strains of ZIKV during early, but not late, pregnancy causes infection of the placenta and fetuses, placental inflammation, neonatal cortical thinning, and short-term neurologic deficits in offspring. More recently, we have demonstrated that placental IL-1β concentrations are elevated in ZIKV-infected dams, and we can reverse the ZIKV-associated short-term neurobehavioral sequelae in offspring by blocking IL-1 receptor signaling during the infection. We hypothesize that placental inflammation following intrauterine ZIKV infection causes perinatal neurological injury, which can then be reversed by targeting maternal IL-1β signaling. While most ZIKV interventions focus on antivirals and vaccines to limit perinatal ZIKV infection, to date no studies have considered the role of maternal and placental inflammation as a mechanism mediating long-term adverse perinatal outcomes following ZIKV infection. Specific Aim 1 will assess the mechanisms mediating elevated IL- 1β signaling in the placenta at different gestational ages following ZIKV infection, the long-term downstream effects of the placental immunopathology and placental IL-1β signaling, and whether these effects are sex- specific. In particular, Aim 1 will determine how placental inflammasome activation, IL-1β release, or engagement of the IL-1 receptor lead to adverse perinatal outcomes. Specific Aim 2 will examine the importance of maternal as opposed to fetal IL-1β signaling in the pathogenesis of perinatal brain injury following ZIKV infection. Using embryo transfer of IL-1β signaling deficient and wild type mouse strains, Aim 2 will assess whether IL-1β activity of maternal origin is critical for sex-specific fetal brain injury. Our novel translational research proposal, utilizing a ZIKV model that we developed, will have a significant impact on perinatal medicine as it will lead to a better understanding of the role of placental inflammation in the pathogenesis of fetal congenital diseases caused by infection or other inflammatory states during pregnancy.",,2024,UNIVERSITY OF MARYLAND BALTIMORE,320456,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2023 +P22227,5K22AI144050-02,Characterization of a human-specific positive regulator of flavivirus infection,"Project Summary/Abstract Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV) or Dengue virus (DENV) are cause of great health and economic concerns worldwide. YFV is the prototypical member of the flavivirus genus, and one of the first human pathogenic viruses that has been identified. Despite the development of a very potent vaccine in the 1930’s, YFV still represents a real theat. Recent outbreaks in Angola and Brazil, over the past two years, occurred in areas with low vaccination coverage. These resurgence events have exemplified the threat and have highlighted the need for the protection of an estimated 400 to 500 million people worldwide. Facing a significant vaccine shortage, fractional doses of vaccine are now used during vaccination campaigns despite no/limited evidence of long-term protection, hence underscoring the urgent necessity of developing novel strategies to clinically manage future YFV outbreaks. Our knowledge of the YFV infectious cycle in vitro and in vivo is extremely limited which has ultimately hampered the development of specific therapies to treat YFV infection, as none is currently available. I recently identified a novel host regulator of YFV infection in human cells that is required for effective YFV infection and replication in vitro. As it is not expressed in mice, this factor could also contribute to the human/primate-specific tropism of YFV. Building on a robust set of preliminary data, I hypothesize that this factor regulates RNA replication or protein translation through direct binding to viral elements. In Aim 1, I will explore the mechanisms by which this factor regulates the replication of the YFV vaccine strain YFV-17D in vitro as well as the host and virus determinants that govern such regulation. In Aim 2, I will determine the role of this factor on the replication of a virulent YFV strain, YFV-Asibi, as well as of other flaviviruses of interest such as ZIKV and DENV. I will also seek to explore the role of this factor using more relevant cell culture system such as primary human hepatocytes by using specific inhibitor of this factor. In Aim 3, I will use a humanized mouse model I recently developed and that is permissive to YFV infection to evaluate the role of this factor on YFV-Asibi and YFV-17D replication in vivo, by treating mice with specific inhibitor of the identified host factor. Altogether, my strong expertise in studying YFV virus in vitro and in vivo, combined with the different viral tracking tools and in vivo models I have previously developed, position me very well to conduct the proposed research. This research could provide novel avenues for the specific treatment of YFV infection and enhance our understanding of the host-pathogen interactions that define flavivirus pathogenicity. This K22 Career Transition Award will help me achieve my scientific and career goals, which consist of transitioning toward an independent assistant professor position and establishing an independent NIH-funded research program aiming at elucidating the mechanisms of flavivirus pathogenicity.",,2024,BOSTON UNIVERSITY MEDICAL CAMPUS,106438,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22228,3R01AI151166-03S2,Metabolic basis of mosquito-endosymbiont-virus interactions RBL Admin Supplement,"PROJECT SUMMARY / ABSTRACT This supplement is responsive to the Notice of Special Interest, NOT-AI-22-049, “Administrative Supplements for NIAID Regional Biocontainment Laboratories (RBL) and other NIH Grantees Conducting Research at RBL- affiliated Sites” and the scope of our NIAID grant, (fund R01AI151166), entitled, “Metabolic basis of mosquito- endosymbiont-virus interactions.” Here, we will accelerate and advance Specific Aims 1-3 of the parent award through two primary supplementary aims; SA 1-3.supp1: Assess how modification of cellular lipids alters the composition of the viral envelope and required structural transitions for maturation and infectivity in Ae. Aegypti. The data generated from SA 1-3.supp1 will significantly enhance the parent award data outcomes as it provides biophysical insight into how lipid modulation might alter virus structure and function and thus impact the viral life cycle in Ae. aegypti. SA 2.supp2: Assess how Wolbachia-mediated lipid changes alter ZIKV and CHIKV infection and virus-associated lipid modulations. The data generated from SA 2.supp2 will significantly enhance the parent award data outcomes by providing additional insight into the metabolic state of the vector following infection with all three vectored viruses. The studies will enhance our understanding of metabolic choke points that may be applicable to all three viruses, and/or significant differences that might hinder biocontrol efforts. Both efforts synergize with the goals of the RBL in (diagnostics, therapeutics, vaccines, and transmission control methods for Arboviruses vectored by Ae. aegypti); and has the full support of the Scientific Director of the RMRBL.",,2025,COLORADO STATE UNIVERSITY,370124,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Vector biology",2020 +P22230,1R01AI168003-01,Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leak,"Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leak ABSTRACT The flavivirus (FV) genus contains medically important mosquito-borne human pathogens that cause a major global disease burden. While dengue (DENV), yellow fever (YFV), and Zika (ZIKV) viruses are systemic, and West Nile (WNV), Japanese encephalitis (JEV), and Zika viruses cause neurotropic infections, each FV can cause severe disease characterized in part by endothelial barrier dysfunction â€Â"" the most classic example being vascular leak in severe dengue. This may result from overproduction of vasoactive cytokines as well as viral factors. The highly conserved FV non-structural protein 1 (NS1) is secreted from infected cells and circulates in the blood of infected humans. We and others have shown that FV NS1 can trigger endothelial barrier disruption in vitro and vascular leak in mice, independently from virus infection. In our current R01, we showed that endo- cytosis of FV NS1 into endothelial cells (ECs) followed by activation of key enzymes such as cathepsin L and heparanase leads to disruption of the endothelial glycocalyx layer (EGL) as well as mislocalization of intercellular junction proteins, both critical for maintaining endothelial barrier integrity. Interestingly, we found that FV NS1 proteins display exquisite tissue tropism, triggering EC dysfunction in vitro and in vivo in a manner reflecting tissue tropism and disease manifestations of each virus. While FV NS1 tissue tropism was determined by differential EC binding and internalization, downstream activation of key enzymes and signaling pathways required for pathogenesis appear to be conserved across FVs. However, host factors, viral determinants, and mechanisms mediating these processes are unknown. We hypothesize that distinct host factors on tissue- specific ECs mediate FV NS1 cell binding and internalization, leading to endothelial barrier dysfunction, virus dissemination, and different FV disease manifestations. In contrast, once a FV NS1 protein is internalized, we hypothesize that downstream steps of EC dysfunction are comparable â€Â"" thus pointing the way to a pan-FV intervention. Here, we expand our previous work by identifying and characterizing host glycans, proteins, and NS1 determinants required for tissue-specific cell binding and internalization of NS1 in human ECs, mouse models, and clinical samples. We also define common mechanisms by which FV NS1 proteins trigger pathology. In Aim 1, we will identify and characterize host glycans and FV NS1 determinants required for differ- ential binding to tissue-specific ECs. In Aim 2, we will identify proteinaceous NS1 receptors required to initiate EC dysfunction and define mechanisms by which FV NS1 proteins mediate disruption of the EGL and intercellular junctions in tissue-specific ECs in vitro and in vivo. Aim 3 investigates the impact of FV NS1-mediated endothelial dysfunction on FV dissemination and pathogenesis in mouse models and human clinical samples from severe dengue and YF patients in Vietnam, Nicaragua and Brazil. This work is supported by experts in glycobiology, FV structural biology and biochemistry, vascular biology, FV pathogenesis and animal models, and clinical investigation and should identify biomarkers of severe FV disease and novel viral and host therapeutic targets.",,2027,UNIVERSITY OF CALIFORNIA BERKELEY,686252,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2022 +P22231,5R21AI156731-02,Mechanism of membrane inactivation method to prepare enveloped virus vaccines,"Project Summary / Abstract The World Health Organization’s list of priority pathogens that pose the highest public health risks, and for which there are insufficient treatments, is composed solely of enveloped viruses. Examples of enveloped viruses highly relevant to human health are: HIV, influenza A viruses (IAV), EboV, MERS-CoV, SARS, SARS-CoV-2, CHIKV, NiV, HeV, RSV, ZIKV, and the influenza A (IAV) and B (IBV) viruses. The human cost of their illnesses is in the millions, and the economic cost is in the hundreds of billions of dollars per year. The standard methods for generating vaccines, including whole inactivated virus (WIV), live attenuated virus (LAV), sub-unit, and DNA/RNA, often fail to result in effective prophylaxis. WIV vaccines have some advantages such as their safety and their presentation of multiple antigens to the immune system. However, WIVs often induce insufficient immunity or even vaccine-enhanced disease due to antigen conformational differences between the WIV vaccine and the challenge virus. Our proposal addresses the pressing need for more effective and broadly applicable WIV vaccines by exploring a promising new technology using the antiviral XM-01 (patent applications pending). Current virus inactivation methods for WIV preparation use chemical or physical means that often damage or modify viral antigens, including the glycoproteins, which are important immunogens for the enveloped viruses. This often leads to non-protective or even destructive immune responses. For example, the efficacies of the currently used WIV vaccines for IAV are between 10%-60%. We recently developed a novel vaccine platform that uses XM-01 to target the viral membrane while largely preserving the native conformation of viral glycoproteins. Preliminary data using IAV as a model indicates that immunization with XM-01-inactivated IAV particles improved induction of neutralizing antibodies to both hemagglutinin (HA) and neuraminidase (NA), as well as animal survival, compared to the traditional formalin-inactivated IAV particles. As XM-01 is a broad- spectrum inhibitor of enveloped viruses, our central hypothesis is that virus inactivation with XM-01 improves WIV vaccine development by preserving glycoprotein conformations, facilitating the effective generation of a protective immune response. We will test our hypothesis with two Specific Aims: Aim 1: Determine the mechanism by which XM-01 inactivated virus affords improved immune responses as compared to traditional WIV vaccine methods, using the influenza virus model. Aim 2: Determine XM-01 vaccination safety, efficacy, and breadth of immune responses. We expect this work will improve our understanding of the mechanism by which XM-01 membrane-mediated viral inactivation generates an enhanced protective immune response, and to assess the new method’s safety, efficacy, and ability to generate broadly protective antibodies against heterologous viral strains, overall assessing whether this new mode of inactivation may be amenable for broad improvement of WIV vaccines.",,2024,CORNELL UNIVERSITY,195501,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Bunyaviridae | Coronavirus | Filoviridae | Flaviviridae | Paramyxovirdiae | Orthomyxoviridae | Poxviridae | Unspecified,Unspecified,,,,,,,,Lassa fever | Crimean-Congo haemorrhagic fever | Rift Valley Fever | COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease | Marburg virus disease | Zika virus disease | Congenital Zika virus disease | Nipah and henipaviral disease | Hendra virus infection | Pandemic-prone influenza | Mpox,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +P22232,3R01NS120895-02S2,Irving Estevez_Diversity Supplement: R01 NS120895,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2025,"RUTGERS, THE STATE UNIV OF N.J.",83816,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22234,5F31MD015674-02,"Characterization of socioeconomic and land use factors related to Aedes aegypti distribution in Maricopa County, Arizona","Project Summary Aedes aegypti mosquitoes are primary vectors of dengue, yellow fever, and the newly emerged threats of Zika and chikungunya viruses. In recent years, mosquito-borne diseases have reemerged as a pressing public health issue around the world, as the geographic range of mosquitoes has increased rapidly due to expanded global trade and travel and potentially due to increased temperatures caused by climate change. Maricopa County, Arizona is potentially at risk for developing Ae. aegypti transmitted diseases due to the established presence of the mosquito vector and the high volume of travelers coming to Arizona from areas with endemic Ae. aegypti- borne disease. In fact, on average, over 25 million travelers cross the border from Mexico (an area with diseases transmitted by the vector) into Arizona each year. Although much research exists on the wide-scale distribution of mosquito vectors, there is less understanding of the local factors that promote mosquito populations or the geographic range of the mosquitoes, especially in a desert climate. It is not known whether there are local socioeconomic or environmental characteristics that support larger Ae. aegypti populations or how mosquitoes move between local populations. We will use a combination of statistical analysis, spatial analysis, and phylogenomic analysis to develop a better understanding of the local factors that support mosquito populations and how mosquito populations are moving over time and space. The long-term goal of this project is to identify small-scale socioeconomic or landscape characteristics that consistently support Ae. aegypti populations and implement interventions with the Vector Control Division in Maricopa County, AZ to reduce mosquito populations, thereby reducing disease transmission risk. The rationale for this application is that the understanding of the distribution, range, and movement of the mosquito populations is a critical component of implementing effective public health efforts that can reduce disease burden and cost by aiming to prevent potential outbreaks of mosquito-borne disease. Hypothesis: Ae. aegypti will not be uniformly distributed throughout Maricopa County, with some areas having larger populations due to differences in infrastructure or landscape characteristics (which are related to neighborhood socioeconomic status) and therefore potential mosquito habitat. Furthermore, we hypothesize that genetically distinct populations will be separated by short distances and will be unique to specific neighborhoods. Aim 1: Characterize the neighborhood socioeconomic factors associated with Ae. aegypti abundance. Aim 2: Characterize landscape traits, such as greenness, that are associated with Ae. aegypti populations. Aim 3: Characterize the origin of and migration between local Ae. aegypti mosquito populations within Maricopa County, Arizona.",,2023,NORTHERN ARIZONA UNIVERSITY,37223,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P22235,3F31MD015674-01A1S1,"Characterization of socioeconomic and land use factors related to Aedes aegypti distribution in Maricopa County, Arizona","Project Summary Aedes aegypti mosquitoes are primary vectors of dengue, yellow fever, and the newly emerged threats of Zika and chikungunya viruses. In recent years, mosquito-borne diseases have reemerged as a pressing public health issue around the world, as the geographic range of mosquitoes has increased rapidly due to expanded global trade and travel and potentially due to increased temperatures caused by climate change. Maricopa County, Arizona is potentially at risk for developing Ae. aegypti transmitted diseases due to the established presence of the mosquito vector and the high volume of travelers coming to Arizona from areas with endemic Ae. aegypti- borne disease. In fact, on average, over 25 million travelers cross the border from Mexico (an area with diseases transmitted by the vector) into Arizona each year. Although much research exists on the wide-scale distribution of mosquito vectors, there is less understanding of the local factors that promote mosquito populations or the geographic range of the mosquitoes, especially in a desert climate. It is not known whether there are local socioeconomic or environmental characteristics that support larger Ae. aegypti populations or how mosquitoes move between local populations. We will use a combination of statistical analysis, spatial analysis, and phylogenomic analysis to develop a better understanding of the local factors that support mosquito populations and how mosquito populations are moving over time and space. The long-term goal of this project is to identify small-scale socioeconomic or landscape characteristics that consistently support Ae. aegypti populations and implement interventions with the Vector Control Division in Maricopa County, AZ to reduce mosquito populations, thereby reducing disease transmission risk. The rationale for this application is that the understanding of the distribution, range, and movement of the mosquito populations is a critical component of implementing effective public health efforts that can reduce disease burden and cost by aiming to prevent potential outbreaks of mosquito-borne disease. Hypothesis: Ae. aegypti will not be uniformly distributed throughout Maricopa County, with some areas having larger populations due to differences in infrastructure or landscape characteristics (which are related to neighborhood socioeconomic status) and therefore potential mosquito habitat. Furthermore, we hypothesize that genetically distinct populations will be separated by short distances and will be unique to specific neighborhoods. Aim 1: Characterize the neighborhood socioeconomic factors associated with Ae. aegypti abundance. Aim 2: Characterize landscape traits, such as greenness, that are associated with Ae. aegypti populations. Aim 3: Characterize the origin of and migration between local Ae. aegypti mosquito populations within Maricopa County, Arizona.",,2023,NORTHERN ARIZONA UNIVERSITY,2591,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P22236,5R35NS122310-02,Research Program Award (R35 Clinical Trial Optional) - Dr. Robyn Klein NINDS,"PROJECT SUMMARY/ABSTRACT Viral infections are now recognized as risk factors for diseases of progressive pathological forgetting, supporting a new paradigm in neuroimmunology whereby innate immune molecules that function as modulators of a variety of normal CNS functions induce neurodegenerative diseases during host-pathogen responses. Studying virus-mediated cognitive dysfunction through the multidisciplinary prism of immunology, neuroscience, and virology is critical for the identification of novel mechanisms of disease, discovery of neuroimaging tools and therapeutic treatments for a wide range of diseases of memory disorder. In my laboratory we made unanticipated, paradigm-shifting discoveries of the roles of CNS infiltrating mononuclear cells in microglial-mediated synapse elimination, disrupted adult neurogenesis, and generation of neurotoxic astrocytes using novel models of recovery from encephalitogenic flaviviruses, West Nile (WNV) and Zika (ZIKV) viruses. We identified classical complement proteins and cytokine receptor signaling as novel molecular mediators that regulate synapse elimination, neural stem cell (NSC) fates, neuron-microglia and microglia- astrocyte crosstalk within cortical structures that regulate memory formation and maintenance. We have also begun leveraging novel neuroimaging modalities to develop biomarkers that may be used to predict and monitor patients at risk for memory disorders. Our aim is to understand the mechanisms that induce alterations in synaptic connections and methods of repair that contribute to disruption of neuronal networks after recovery from viral infections. Our research program focuses on three broad areas related to the roles and regulation of innate immune molecules involved in spatial learning using novel murine models of post-infectious cognitive dysfunction. First, using genetic, pharmacologic and PET-MRI, we will identify and define molecular interactions between T cells and microglia or neurons that drive the generation and maintenance of resident memory T cells that promote cognitive dysfunction. We will use scRNAseq under BSL3 conditions to screen for genes and pathways to be targeted via cell-specific deletion of cytokine or chemokine receptors, or administration of agents that inhibit or enhance pathways. We will also develop diagnostic tools that employ ABSL3 PET-MRI. Second, we will define how microglia-astrocyte-NSC interactions in the context of recovery from CNS viral infections limit repair and recovery. We will use global and conditional gene targeting in mice to delineate the in vivo roles of cytokines in neural cell types that regulate astrocyte inflammasome activation and its relationship to neuronal and synapse recovery. We will also define innate immune mechanisms that direct and maintain astrogenosis during acute viral infection and recovery using PET-MRI detection of P2X7R, a marker of reactive astrocytes. Finally, will utilize reporter mice/fate mapping, bone marrow chimeras and scRNAseq to delineate the cytokine-mediated roles of myeloid cells in the generation of neurotoxic astrocytes during WNND recovery. Third, we will examine innate immune mechanisms triggered after viral infections that negatively impact cortical connectivity and determine whether neuroimaging can be used to predict and follow this process. Specifically, we will combine genetic approaches with functional optical intrinsic signal imaging of hemoglobin and calcium dynamics to define mechanisms that negatively impact cortical connectivity. Our research program will define new concepts in the molecular neuroimmunological regulation of synapses, T cell and glial interactions, inform studies of related processes throughout the nervous systems, and will likely enhance our understanding of neurodegenerative and other disorders of memory.",,2029,WASHINGTON UNIVERSITY,1181250,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22237,272201800013I-0-759302200001-1,Task V12: CLINICAL SAMPLE TESTING FOR ZIKA VIRUS VACCINES,The Evaluation and Testing Services (ETS) for Vaccines and Other Biologics for Infectious Diseases contract provides a variety of product development services from early feasibility studies through activities required for the submission of Biologic License Application (BLA) and/or Investigational New Drug (IND) applications.,,2022,BATTELLE CENTERS/PUB HLTH RES & EVALUATN,211025,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P22239,3R01NS120895-02S1,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",89119,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22240,1K08AI168569-01,Defining Molecular Epitopes of Protective Antibodies to Flaviviruses,"Project Summary/Abstract: The objective of this K08 Mentored Clinical Scientist Career Award Application is to provide Dr. Alena Markmann with a strong foundation in human immunology and the latest methods for studying human immune cells before launching her independent research career on the human immune response to RNA viruses. Dr. Markmann is an Assistant Professor of Medicine, tenure track, at the University of North Carolina -Chapel Hill (UNC) School of Medicine with a joint appointment in the Department of Microbiology and Immunology. The candidate has expertise in and a strong track record of publications on antibody structure, antibody-antigen interactions and antibody neutralization of viruses. By strengthening her knowledge of adaptive immunity to RNA viruses and mastering the latest methods for analyzing antigen specific B cells, Dr. Markmann will study how the human immune response to emerging flaviviruses like dengue and Zika can suppress viral infection and disease or enhance viral replication and exacerbate disease. The candidate and her mentor Dr. Aravinda de Silva have designed a training plan that includes a rigorous research component along with didactic instruction, networking and presentation opportunities, team management skills as well as manuscript writing and grantsmanship. Together these skills will establish the methods and principles necessary for successful career development. Flaviviruses are enveloped positive stranded RNA viruses that pose a growing threat to the human population and cause millions of infections annually. They are vector-borne, transmitted by ticks and mosquitoes, and cause a spectrum of disease manifestations including febrile illness, encephalitides that can cause lifelong complications, Congenital Zika Syndrome and dengue hemorrhagic fever and shock syndromes. For the most part, flaviviral infection result in a neutralizing protective antibody response against the infecting virus, that can last for years after infection. The four dengue viruses however are very similar antigenically and in many cases, result in generating a broad cross-neutralizing antibody responseto dengue virus serotypes that individuals have not yet been exposed to. Thus far, no one has identified the viral target site of these broadly neutralizing dengue antibodies that exist in the serum. Furthermore, though we know of a few major targets of the Zika protective antibody response from studying memory B cells, we do not know what the serum targets are. Preliminary results suggest that in the case of Zika serum antibody responses, binding targets are correlated with known strongly neutralizing memory B cell-derived antibody targets. Thus, we hypothesize in Aim 1, that serum antibody responses will mirror memory B cell responses, but will likely come from a smaller number of B cell clones and be less cross-reactive with other flaviviruses. In Aim 2 we will identify the viral binding targets of broadly cross- neutralizing dengue antibodies from the serum. These studies will result in the ident ification of critical protective viral targets to both dengue and Zika viruses from the serum antibody compartment in order to inform successful vaccine design.",,2027,UNIV OF NORTH CAROLINA CHAPEL HILL,195235,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22241,5R01NS120895-02,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",382697,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22242,5R01AI156187-02,Probing Functional States and Inhibition of Flaviviral Proteases Using Nanopore Tweezers,"Project Summary Flavivirus are major mosquito-borne pathogens infecting millions of people worldwide each year. Currently there is no antiviral therapy available for treating West Nile, Dengue and Zika viral infections. The first vaccine CYD- TDV (Dengvaxia) against DENV was approved last year but shows only 56% overall efficacy against the four dengue serotypes. The flaviviral two-component NS2B/NS3 protease is required for viral replication and thus an attractive antiviral target. However, extensive screening and rational design efforts have failed to identify any clinically viable inhibitors at this point. Two key factors have likely contributed to the challenge. First, traditional screening efforts rely primarily on binding affinity to predict the drug efficacy. Yet, increasing evidence has emerged to show that the residence time of drug-target interaction is a more reliable predictor of in vivo pharmacological activity. These kinetic rate parameters are generally not available during early stages of drug discovery. Second, NS2B/NS3 proteases display complex conformational dynamics during function and inhibition, which is still poorly understood. This project aims to develop a new label-free single molecular approach to resolve the conformational states of NS2B/NS3 proteases. Key to the approach is the use of an innovative nanopore tweezers where the protease is confined with the pore lumen, allowing dynamic structural changes during substrate or inhibitor binding to be continuously monitored by current fluctuation signals. Analysis of the current traces will provide a complete profile of binding affinity and kinetic rates as well as the distribution of conformational states. Specifically, we will first build a nanopore tweezers tool set that is readily tunable for trapping various flaviviral proteases. Secondly, we will track and analyze the functional states of the NS2B/NS3 protease in the presence of various substrates. Influence of critical residues, substrate, construct design on the dynamic equilibrium between the “open” and “closed” states will be assessed to provide insight into the mechanism of protease activity. Finally, the nanopore tweezers will be deployed to determine the structural dynamics and binding thermodynamics and kinetics profiles of NS2B/NS3 interacting with various inhibitors. Once the inhibition profiles are established, the nanopore tweezers confined NS2B/NS3 system will be tested for screening a diverse compound library to identity novel allosteric inhibitors with improved drug-like properties compared to active-site inhibitors. This work will provide unprecedented kinetic information on the function- structural dynamics relationship of NS2B/NS3 complex and mechanisms of substrate binding and inhibition, as well as establish a new paradigm for high-throughput drug screening that is independent of enzymatic activity.",,2026,UNIVERSITY OF MASSACHUSETTS AMHERST,441244,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +P22243,5F32HD103313-03,Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection,"PROJECT SUMMARY The Brazilian Zika virus outbreak of 2016 initiated an international public health crisis when it became clear that babies infected in utero were being born with devastating neurological defects. In addition, troubling reports have shown that many infected babies present as “neurologically-normal” at birth but experience later atypical developmental and neurosensory alterations into infancy. The long-term developmental consequences of Zika infection are currently unknown, but mechanisms of its pathobiology have been linked to the preferential injury of axons and myelin. Disrupted or delayed myelination in early life has been previously associated to significant and permanent impairments across domains of sensory, motor, and cognitive abilities. To investigate the impact of fetal Zika infection on postnatal brain development, this study will acquire quantitative magnetic resonance imaging metrics of myelin and axon maturation in an established nonhuman primate model at 6, 12, 24, and 30 months of age (equivalent up to ~ age 10 in humans). This proposed work, therefore, takes a novel approach by tracking whole brain changes in tissue microstructure, in vivo, in an accelerated model of brain development and links those changes to cellular anatomy, post mortem. Behavioral outcomes related to axon and myelin injury will also be investigated. The aims of this proposal have been designed for direct translation to human studies and will establish a valuable resource for predicting and interpreting outcomes of fetal Zika infection.",,2023,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,46628,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +P22244,5K08AI156126-02,Defining mechanisms of Zika-virus associated microcephaly: cell population dynamics and gene expression in infected human cerebral organoids and neural progenitor cells,"PROJECT SUMMARY/ABSTRACT Zika virus swept across the Americas in 2015-16, and it was during this epidemic that the teratogenic consequences of congenital Zika infection were first described. Despite extensive research, it remains unknown how Zika infection causes microcephaly, or whether this pathology is unique to recent strains, Two new tools will facilitate discovery in this area. First, we and others have shown that the human stem cell derived cerebral organoid is a tractable neurodevelopmental model in which to study Zika infection. Second, we have demonstrated that single cell sequencing techniques that enrich for poly-adenylated mRNAs can identify flavivirus-infected cells â€Â"" an unexpected result given flavivirus genomes do not have poly(A) tails. The goal of this study is to determine the mechanisms by which Zika virus disrupts fetal brain development, building on these technical advances. We will employ single cell RNA-sequencing to identify and compare cellular populations in organoids over time, in the presence and absence of Zika virus. This will allow us to distinguish pathogenic disruptions in a) stem cell abundance, b) cell division, and c) differentiation. We will use single cell RNA-sequencing and ribosome profiling to define gene expression responses to Zika infection in neural progenitor cells, thought to be the target of Zika virus in the fetal brain. By comparing viruses of varying pathogenicity in these studies, we will identify differences in host gene expression and viral replication associated with disease severity. The proposed study will address a major unresolved problem in the field of Zika virus pathogenesis, contribute broadly to our understanding of cerebral development, and mature cutting edge technologies for the investigation of questions at the interface of infection and development. The project will be developed under the mentorship of Dr. Lee Gehrke, a leader and expert in the field of RNA virology with a background in developmental biology. Additional scientific and career guidance will be provided by a scientific advisory committee composed of experts in virology, single-cell sequencing, stem-cell derived tissue models, and pediatric infectious disease pathogenesis. The training program will include coursework in computational biology, training in molecular and tissue culture techniques, workshops in leadership, and didactic learning from local seminars as well as national and international conferences. Research and training will occur at the MIT Institute for Medical Engineering and Science, and at Boston Children’s Hospital at the Harvard Medical School. Together, MIT and Harvard Medical School afford extensive resources and expertise in all aspects of the proposed research. Boston Children’s Hospital is a supportive environment committed to providing 85% protected time for this research, and offers workshops in career development and leadership to prepare early-stage investigators for independence. The project will build on the candidate’s background in virology and high-throughput sequencing, allow her to mature as a physician-scientist, and position her to achieve her goal of an independent research career in pediatric infectious disease pathogenesis.",,2022,BOSTON CHILDREN'S HOSPITAL,194940,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22245,5R21AI166878-02,Haploid-resolved genome assemblies for the arboviral vectors Aedes aegypti and Aedes mascarensis,"Haploid-resolved genome assemblies for the arboviral vectors Aedes aegypti and Aedes mascarensis Project Summary/Abstract Aedes aegypti transmits several arboviral diseases including dengue and Zika fever, which threaten half of the human population worldwide. In this study, we will take advantage of Oxford Nanopore Technology (ONT) sequencing, the TrioCanu binning approach, and Hi-C scaffolding to create haploid-resolved chromosome- level genome assemblies for Ae. aegypti and Ae. mascarensis. These two closely related species show reproductive isolation by hybrid breakdown via formation of intersexes in backcross hybrids. The long-term objective of this research is to decipher the genetic mechanisms of reproductive isolation between Ae. aegypti and closely related species and to translate such fundamental knowledge into safe and efficient methods to control mosquito-borne infectious diseases. Understanding the permeability of species boundaries is increasingly urgent because of recent developments in transgenic- and gene drive-based applications to control disease vectors. The major goal of this proposed R21 project is to develop and validate phased or haplotype-resolved genome assemblies for Ae. aegypti and Ae. mascarensis and use them for identification and characterization of the genomic regions associated with intersex phenotypes in backcross hybrids between the two species. This timely project will meet the demand for new, highly-finished genome references for arboviral vectors based on appropriate innovative tools and the PI’s and Co-I’s expertise. Toward this goal, we propose the following three Specific Aims: (1) Obtain contiguous haploid genome assemblies for the Ae. aegypti RED strain and Ae. mascarensis by integrating ONT, Illumina sequencing, trio binning, and chromosome-scale Hi-C scaffolding; (2) Validate the obtained assemblies and construct high-resolution physical genome maps for Ae. aegypti and Ae. mascarensis using fluorescence in situ hybridization (FISH); and (3) Identify genomic regions in chromosome 1 that are associated with intersex phenotypes. The new, haploid-resolved chromosome-level genome assemblies for Ae. aegypti and Ae. mascarensis will be available to the scientific community through VEuPathDB and NCBI. Identification of the recombination breakpoints and characterization of genomic regions associated with intersex phenotypes will improve our understanding of the mechanisms that maintain species boundaries and determine sex in mosquitoes. The project will also help us to detect genome variations between these two species that may be important for speciation, adaptation, and vectoral capacity.",,2024,VIRGINIA POLYTECHNIC INST AND ST UNIV,195322,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22246,1K23AI168581-01,Arbovirus Prediction and Mitigation in the Indo-Pacific,"Project Summary / Abstract Dengue, a potentially life-threatening disease, has increased 30-fold in the last 50 years. In Indonesia, 1 in 3 children have had a dengue infection by 5 years old. Islands in the Indo-Pacific are highly vulnerable to climate change and water insecurity, two key drivers of arbovirus spread. Predicting and mitigating arbovirus transmission in the Indo-Pacific is critical to addressing the increasing risk of arboviruses in the U.S. In the next several decades, half the U.S. may have habitat suitable for Aedes aegypti and Ae. albopictus, mosquitos which spread dengue, chikungunya, Zika, and yellow fever viruses. Revitalizing Informal Settlements and their Environments (RISE) is a cluster randomized control trial evaluating the benefits of upgrading local water infrastructure in urban slums in Indonesia and Fiji. The RISE intervention is a prototype for future slum upgrading to address climate change and water insecurity throughout the Indo- Pacific. Although the World Health Organization recommends permanent environmental modification as an arbovirus control strategy, this has never before been rigorously tested. RISE provides an important opportunity to evaluate whether this model decreases or inadvertently increases arbovirus transmission. In addition to evaluating a new paradigm for mitigating arbovirus transmission, RISE is an ideal platform to assess gaps in knowledge about environmental drivers of arbovirus transmission. My hypothesis is that modifiable environmental conditions drive arbovirus transmission in these communities. To test this hypothesis, I will leverage the RISE platform to study arbovirus risk factors in this region and evaluate the impact of permanent environmental modification on arbovirus transmission in urban slums. I will also create a mathematical model to simulate arbovirus transmission in this region under a range of climate change and intervention scenarios. I have developed a customized career development plan that aligns with my proposed research. It incorporates both formal and informal training under the mentorship of Drs. LaBeaud and Luby. This training plan draws upon my existing expertise in global health, tropical medicine, and epidemiology; it will enhance my expertise in laboratory diagnostics, geospatial analysis, and mathematical modeling. The planned didactics and technical training included here will provide the foundation necessary to achieve my goal of becoming an academic physician focused on mitigating the spread of infectious diseases in the era of climate change.",,2027,STANFORD UNIVERSITY,193320,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector control strategies | Impact/ effectiveness of control measures,2022 +P22249,1R35GM147498-01,Modulating gene expression by RNA-targeting chimeras,"PROJECT SUMMARY RNA-binding small molecules have the potential to modulate the expression of genes whose protein products were previously considered “undruggable.” Risdiplam, targeting a precursor mRNA, was recently approved for the treatment of spinal muscular atrophy (SMA) and demonstrates the specificity and safety attainable by this approach. Although a variety of small-molecule scaffolds have been uncovered as RNA-binding ligands, their use is hampered by (1) lack of specificity and (2) unpredictable function. We propose a research program that will provide RNA-targeting chemical probes that will avoid these drawbacks. Inspired by Proteolysis Targeting Chimera (PROTAC) technology, we are designing chimeric molecules that will target RNA specifically and carry (deliver) the ability to induce RNA degradation or inhibit RNA translation, in a highly predictable manner. Our initial efforts towards an RNA-targeting chimera platform use a newly discovered RNA-binding coumarin derivative as a model and fine-tune its preferential binding properties through chemical modification. Through structural optimization, which includes using a “bidentate” RNA ligand strategy, we expect to achieve RNA-binding selectivity equal to or greater than that of oligonucleotides. At the same time, we propose to develop and optimize three novel effectors to precisely degrade RNA targets or inhibit the target RNA translation. These new effectors have shown promising results in inhibiting Zika virus (an RNA virus) gene expression. Ultimately, our proposed work will generate a top-down method for designing selective gene expression inhibitors that are independent of the gene's protein product. The long-term goal of our lab is to build a medicinal chemistry platform for making gene-specific and patient-specific therapies using RNA-binding small molecules. In this process, we will not only generate various tool compounds for studying important disease-modifying genes, but also combine computational and experimental technologies to understand the detailed mechanism of RNA-small molecule recognition.",,2027,UNIVERSITY OF KANSAS LAWRENCE,382500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22252,3DP1DA051144-03S1,A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups,"ABSTRACT Substantial evidence now indicates that HIV-infected individuals are at a significantly elevated risk for severe COVID-19 disease when infected with SARS-CoV-2. Moreover, persons who use and inject drugs (PWUD and PWID) have a high-risk of HIV infection and exposure to SARS-CoV-2 and face major barriers to accessing antiviral therapies (i.e., are often immunocompromised). The problem is further exacerbated by the emergence of SARS-CoV-2 variants that escape vaccine-mediated immunityâ€Â""it is now evident that immunocompromised individuals promote the evolution of SARS-CoV-2 escape variants and HIV-infected PWUD/PWID with barriers to treatment represent such a population. Consequently, there is a critical unmet medical need for new therapeutics that could treat HIV as well as SARS-CoV-2â€Â""particularly the emerging variants of concern’â€Â""and could be effectively deployed in difficult-to-reach, high-risk populations (e.g., PWUD/PWID). The long-term goal of this work is to develop single-administration therapies for HIV-1 and SARS-CoV-2 variants to effectively reach PWID/PWUD populations. The specific objective of this supplement proposal is to test efficacy of our recently developed Gene Drive Therapies (GDT) against HIV and SARS-CoV-2 variants in patient cells from HIV+ PWID. This effort will build heavily off our recent success in engineering GDTs for HIV-1 (see Parent Award) and Zika Virus (ZIKV), as well as our extensive preliminary in vitro data showing efficacy of GDTs against SARS-CoV-2 variants. The central hypothesisâ€Â""based on our extensive preliminary in vitro studiesâ€Â""is that our engineered GDT candidates will have the capacity to reduce both SARS-CoV-2 viral load and pathogenesis, including of SARS-CoV-2 variants of concern, and HIV viral load, thereby serving as a single-administration, combination therapeutic for HIV-1 and SARS-CoV-2. The rationale for a GDT for SARS-CoV-2 is based on our preliminary data showing that GDTs significantly reduce SARS-CoV-2 replication in cell culture, are equally effective against CoV-2 variants and from extensive studies on HIV-1 in humanized mice and positive FDA meetings. We will achieve our objectives via two specific aims: (i) Quantify in vivo efficacy of the recently developed GDT in reducing SARS-CoV-2 viral replication and pathogenesis in hamsters; and (ii) Develop a lung-organoid co- culture to test efficacy of GDTs against HIV-1 and SARS-CoV-2 in patient-derived cells from HIV+ PWIDs. While the GDT approach carries inherent risks, single-administration therapeutics active against both SARS-CoV-2 variants and HIV would be highly beneficial, particularly for treating difficult-to-reach, high-risk PWID populations. The studies proposed here will also have broad fundamental significance by establishing a novel culture model and tool to assay how SARS-CoV-2 and HIV infections interact in the PWUD/PWID setting (i.e., in the context of Substance Use Disorders (SUDs) in at-risk populations) and will provide in vivo validation of a novel medical countermeasure with therapeutic efficacy against emerging SARS-CoV-2 variants.",,2025,J. DAVID GLADSTONE INSTITUTES,189000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +P22253,1D43TW012246-01,Training and Research on Arboviruses and Zoonoses In Nigeria and Sierra Leone (TRAIN),"ABSTRACT Emerging viral diseases comprise several of the greatest global risks to human health, and West Africa is a source and epicenter for several. These include arthropod-borne viruses (arboviruses), such as chikungunya, Zika, and yellow fever with African origin and both ancient and recent histories of spread to Asia and the Americas to initiate massive epidemics. Dengue also increasingly recognized in Africa as a major public health problem. Zoonotic African hemorrhagic viruses also caused unprecedented outbreaks during the past decade. In 2014, the first West African epidemic of hemorrhagic fever attributed to Ebola virus spread to several countries including Sierra Leone, representing by far the most devastating filoviral outbreak on record with over 11,000 fatalities. Lassa virus, causing an estimated 100,000-300,000 hemorrhagic fever cases in Africa annually, produced an unprecedented 2018-2019 epidemic in Nigeria. The mechanisms whereby these zoonotic viruses emerge remain obscure along with understanding of their true disease burden and varied clinical disease and sequelae outcomes. To address these challenges, we will develop a new generation of West African scientists to predict, prevent and contain emerging viral diseases through multidisciplinary scientific and public health training. Leveraging our West African Center for Emerging Infectious Diseases (WAC-EID, NIAID U01AI151801), outstanding research leaders in West Africa, and the exceptional breadth of expertise in emerging viral diseases at the University of Texas Medical Branch (UTMB), we will provide multidisciplinary training for young scientists from two leading universities: Njala University in Sierra Leone and Jos University in Nigeria. The aims of Training and Research on Arboviruses and Zoonoses In Nigeria and Sierra Leone (TRAIN) include: 1. Provide general on-site training at Njala and Jos Universities to Master’s/PhD students enrolled in the local graduate programs; 2. Provide specialized training at UTMB on the most advanced methods and techniques for expertise transfer to Sierra Leone and Nigeria; 3. Provide on-site research training at Njala and Jos Universities to ensure successful local implementation of the program, which will include education of laboratory technicians/managers among others; 4. Integrate trainees into the WAC-EID’s research programs to gain hands-on experience in surveillance activities, diagnostics and data management. Five trainees per year will participate in short-, medium-, and long- term training phases at UTMB and in W. Africa. Training activities will include didactic courses, online modules, field training, molecular/virological techniques including the study of animal models and pathogenesis, biosafety training, and lab management education. Upon the completion of our training program, these young scientists will play critical roles in surveillance to better understand the circulation of emerging viruses in the region, mechanisms of emergence, virus discovery, epidemic transmission, pathogenesis, and countermeasures to mitigate emerging viral threats. The local training programs are designed to be sustainable, and the 3-way research and training partnerships will broadly benefit science and public health throughout the region.",,2027,UNIVERSITY OF TEXAS MED BR GALVESTON,252400,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22255,5U01AI151807-03,Coordinating Research on Emerging Arboviral Threats Encoing the Neotropics (CREATE-NEO),"Project Summary In recent decades, Central and South America have experienced spillover of endemic arthropod-borne viruses (arboviruses) from wildlife reservoirs into humans, exchange and recombination of emerging arboviruses within the region, resurgence of arboviruses previously controlled by vaccination or vector control, introduction and spread of novel arboviruses, and exportation of viruses to other regions. Furthermore, there is great concern that newly-introduced Zika virus may spill back into an enzootic transmission cycle in the Americas. Central and South America encompass enormous vertebrate and invertebrate biodiversity, and these species harbor a broad range of arboviruses whose risk of spillover and spread in humans is presently unknown. Increases in the rates of global travel, invasion of novel vector species, urban expansion, deforestation, and global climate change all elevate the risk of further arbovirus emergence, as does the breakdown of public health structures in Venezuela. The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE- NEO) project will provide a network of surveillance sites in the neotropics coupled to cutting-edge modeling approaches in order to anticipate and counter emerging arboviruses. Aim 1 will identify novel and known arboviruses as well as the host-vector networks that sustain transmission of these viruses within the neotropics, map the spatial distribution of these transmission networks, and characterize virus transmission dynamics within these networks. To do so, we will collect mosquitoes and other vectors as well as non-human primates and other vertebrate hosts at multiple sites in areas of high and varied biodiversity in Panama and Brazil and screen these samples for known and novel arboviruses. These data will then be analyzed using niche modeling, machine learning to predict undiscovered hosts and vectors, and dynamical transmission models. Aim 2 will focus on prospective and retrospective analysis of human infection and disease. To do so, we will leverage ongoing human clinical cohorts at multiple sites in Brazil and Panama. We will extend and expand these cohorts, with a particular focus on the immune-mediated interactions among multiple arboviruses at sites of hyperendemicity. We will also develop novel diagnostics to capture known and novel arboviruses and model the impact of human and non-human primate movement on spillover and spillback of target arboviruses. Data and models generated via these two aims will forewarn local, regional and global public health agencies of arboviruses within Central and South America that pose particularly high risk of spillover, emergence into transmission among humans, and/or international spread. Moreover CREATE-NEO will build local capacity to predict, detect and respond to emerging arboviruses at their point of origin, thereby maximizing the potential to avert full-blown emergence.",,2025,UNIVERSITY OF TEXAS MED BR GALVESTON,1536375,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Immunity | Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping,2020 +P22257,5R01AI154844-02,Essential early events in the flavivirus lifecycle,"Project Summary Arthropod-borne flaviviruses such as dengue virus, West Nile virus, yellow fever virus (YFV), and Zika virus, are a major cause of human disease. We are studying the early, post-fusion and pre-replication events in the flavivirus lifecycle by using the prototype flavivirus, YFV, as our model. Our overarching hypothesis is that flaviviruses, which alternately replicate in vertebrate and invertebrate hosts, have evolved to use i) highly conserved factors shared between hosts; and ii) multiple, redundant factors that may not be well conserved between hosts. Therefore, discoveries made with YFV will be validated and studied by comparison to other flaviviruses and between human and mosquito cells. Aim 1 focuses on the post-fusion process of nucleocapsid uncoating, dissecting the mechanisms by which cells unlock this fateful cargo. Aim 1 is a logical extension of our Preliminary Data showing that the delivery of a translatable YFV genome requires cellular ubiquitylation and VCP/p97, a cellular ATPase that extracts ubiquitylated proteins from large macromolecular complexes. Aim 2 focuses on identifying the cellular protease(s) that cleave the viral NS1-2A polyprotein intermediate. Cleavage is essential for flavivirus replication (shown here), yet the identity of this protease has remained elusive for over two decades. We have identified a small family of related candidate NS1-2A proteases and are validating their activity by rigorous, combinatorial genetic ablation. These efforts will solve long- standing puzzles in flavivirus gene expression and replication and identify targets for future development of broadly acting antivirals.",,2026,YALE UNIVERSITY,418750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22258,5R01AI143698-03,Understanding mosquito movement and its relevance to control through genetic analysis,"PROJECT SUMMARY/ABSTRACT: Dengue, Chikungunya, Zika and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. Consequently, there is interest in novel strategies to control these diseases, including the release of genetically sterile male mosquitoes, mosquitoes transfected with Wolbachia, and mosquitoes engineered with gene drive systems. The safety and effectiveness of these strategies and considerations regarding trial design and implementation are critically dependent upon a detailed understanding of mosquito movement at both fine and broad spatial scales, yet there are major gaps in our understanding of these movement patterns. The declining cost of genome sequencing and novel methods for analyzing geocoded genomic data provide opportunities to address these knowledge gaps. In this project, we propose to devise a robust approach for inferring fine-scale mosquito dispersal patterns and their impact on innovative vector control strategies. We propose to use in silico simulations of mosquito ecology and preliminary geocoded mosquito genomic data collected from Fresno, California to determine sampling routines capable of quantifying dispersal patterns, population sizes and mating patterns using genetic kinship analyses (Aim 1). Results from these analyses will iteratively inform sampling schemes for two rounds of subsequent collections of Aedes aegypti, the mosquito vector of dengue, Chikungunya and Zika viruses, in Yishun, Singapore (Aim 2). Genome sequencing and kinship analyses will be used to quantify Ae. aegypti movement patterns, population sizes and mating behaviors at this location, and to parameterize spatially-structured 3D models of Ae. aegypti population dynamics. The resulting models will be used to explore biosafety, trial design and implementation considerations for novel vector control strategies including: i) population suppression systems such as Wolbachia-infected males and genetically sterile males, and ii) population replacement systems such as population transfection with Wolbachia, localized systems such as chromosomal translocations, and non- localized systems such as homing-based gene drive (Aim 3). We expect the proposed research to lead to the development of greatly enhanced surveillance strategies to infer fine-scale mosquito movement patterns and other demographic parameters, and to help inform the safe application of several novel and highly promising strategies for the control of dengue, Chikungunya and Zika viruses and other devastating mosquito-borne diseases.",,2025,UNIVERSITY OF CALIFORNIA BERKELEY,520611,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22260,1R21AI168716-01,Conserved molecular mechanisms of replication for mosquito-borne flaviviruses,"As obligate intracellular parasites, all viruses replicate by coopting host machinery through virus-host protein interactions. Arthropod-borne viruses, which are transmitted to vertebrates by arthropod vectors, must hijack host machinery in human and arthropod cells to accomplish the same fundamental aspects of virus replication. Thus, arthropod-borne viruses maintain protein interactions with host homologs (interologs) to replicate. Identifying these interologs is critical to understanding how an important group of viruses deals with this unique constraint from a biophysical perspective. For flaviviruses transmitted by Aedes mosquitoes (Aedes-borne flaviviruses), it can also inform therapy development by expanding the list of drug targets since these viruses are a major source of human disease. Using a comparative proteomics approach, we recently found large-scale evidence of interologs for dengue virus (DENV), a major Aedes-borne flavivirus that infects nearly 400 million people annually. These interologs involve processes that are essential for virus replication in human and Aedes cells. We hypothesize that Aedes-borne flaviviruses use the conserved interologs to facilitate replication in human and Aedes cells due to the similar constraints place on these viruses and the complexity of maintaining virus-host protein interactions across multiple divergent hosts. The overall objective of this proposal is to systematically compare the role of interologs in virus replication for two Aedes-borne flaviviruses. We will focus on DENV to take advantage of our existing interolog data and yellow fever virus (YFV), a re-emerging Aedes-borne flavivirus that is distantly related to DENV. In Aim 1, we will systematically identify YFV-human and YFV-Aedes protein interactions using affinity purification and mass spectrometry. We will further identify YFV interologs through computational network integration. In Aim 2, we will identify interologs conserved between YFV and DENV using a similar computational network integration approach. We will then test the role of interologs in Aedes-borne flavivirus replication by measuring virus replication following interolog knockdown. This work will identify the conserved molecular mechanisms by which a medically important group of viruses replicates. It will reveal the biophysical parameters that constrain virus evolution. In the future, the interologs we identify could be leveraged as pharmacological or vector engineering targets to inhibit replication of multiple Aedes-borne flaviviruses. Our work would also lay the foundation to search for more interologs conserved across different arthropod vectors and/or different virus families.",,2024,UNIVERSITY OF CALIFORNIA AT DAVIS,199350,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Vector control strategies",2022 +P22262,5R21AI159459-02,Non-invasive approaches to mosquito-borne pathogen surveillance using excreta,"Project Summary Mosquito-borne diseases are expanding rapidly across the globe. Recent outbreaks of West Nile, dengue, chikungunya and Zika viruses have sickened hundreds of millions of people, while parasites such as malaria kill over 400,000 annually. The spread of competent vectors and their pathogens to new continents and climates, coupled with the recent rapid global expansion of other novel RNA viruses that infect humans, emphasizes the need for rapid and reliable pathogen surveillance techniques now more than ever. Early detection ensures that vector control efforts are directed to the right location at the right time to avert a potential epidemic. Surveillance and detection of infected mosquitoes is often an early predictor of impending human infection however comes with challenges, including the time involved to sort, identify and extract RNA from large numbers of mosquitoes while maintaining a cold chain. This requires that mosquito surveillance, identification, and pooling precede virus testing. It has recently been shown that mosquitoes with a disseminated infection excrete (as excreta/feces) arbovirus and parasites in concentrations suitable for detection when sampled in the lab. This allows for rapid and non-destructive sampling and pathogen testing, however current field trapping devices are unable to efficiently collect the randomly distributed ca. 1.5 Ã'µL excreta droplets. To address this issue, we propose here to design two novel excreta-collecting mosquito traps for host-seeking and ovipositing (or gravid) mosquitoes, respectively, that utilize sugar feeding stations and a custom fabricated collection system composed of a nanostructured superhydrophobic surface to funnel and condense the excreta sample. An appropriate hydrophobic surface conformation will first be selected and tested for efficacy during initial field trials. This prototype will then be scaled up and configured to trap wild mosquito populations while channeling and aggregating excreta produced within the trap to a standard microcentrifuge tube attached externally for quick and easy collection. To test the ability of both devices to effectively sample potential pathogens from trapped mosquitoes, the traps will be deployed across five New Jersey counties spanning a multitude of mosquito habitat in collaboration with county mosquito control agencies. The captured excreta will be subject to metavirome sequencing to identify and assemble genome data from the full breadth of both known and potentially novel RNA viruses in the samples, representing a broad diversity of New Jersey mosquitoes. This project represents a foundational step towards sentinel “mosquito free” surveillance of vector-borne pathogens that will facilitate rapid response to mitigate enzootic outbreaks before they occur.",,2024,"RUTGERS, THE STATE UNIV OF N.J.",181988,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22263,1R21AI166633-01A1,Influence of sleep-like states on mosquito behavior and physiology,"Project summary Sleep is critical for nearly all animals. This state is characterized by a specific set of parameters for each species however there is a lack of sleep-based studies in mosquitoes. This should be considered a major knowledge gap in mosquito biology and potentially hinders the development of new control methods and our understanding of factors influencing vectorial capacity. Our preliminary studies suggest that there will likely be explicit factors underlying mosquito sleep, which need to be fully characterized to define this biological state in mosquitoes. The focus of the proposed work is to provide the first extensive characterization of mosquito sleep. After sleep has been defind, studies on the manipulation of sleep will discern how reduced sleep (e.g., induced by human activity in urban areas) may alter behavioral and physiological aspects of mosquitoes such as host preference, blood- feeding, reproductive output, and viral transmission. These studies are supported by the following: 1) Historic and our preliminary observations of putative sleep postures of mosquitoes, 2) Initial activity monitoring results that establish that day and night active mosquitoes sleep at higher rates during the night and day, respectively, 3) targeted studies suggesting that sleep can be prevented by mechanical disturbance that impacts subsequent host landing, 4) Preliminary data showing a reduction of spontaneous neural activity after prolonged rest, 5) Our development of novel sensory deprivation equipment that allows for mosquito observation without host interference to pinpoint differences that could be related to mosquito sleep-like states, and 6) Integrative and innovative experimental design that ranges from basic behavioral analyses to neuronal recording that will provide an encompassing view of the mosquito sleep state. This study has two specific aims: Specific Aim 1. Establishing the characteristics associated with sleep-like states in mosquitoes. Specific Aim 2. Defining shifts in mosquito fitness, behavior, and viral transmission following sleep deprivation. Upon completion of these specific aims, our expected outcomes are to have defined sleep-like states in mosquitoes and, subsequently, how sleep deprivation impacts a range of epidemiologically relevant biological aspects. This will be transformative to the research field and will set the stage for multiple lines of research. Most importantly, these studies will create a novel paradigm, where aspects of mosquito biology should be measured under two independent periods: a non-resting (no sleep) and sleep-like status. Finally, our anticipated results are likely to inform on the adaptations of mosquitoes to urban areas where host activity patterns and light/dark conditions are decoupled from day/night successions and could impact sleep, mosquito-host interactions, and potentially patterns of disease transmission.",,2024,UNIVERSITY OF CINCINNATI,202120,Disease Vectors,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22264,5R21AI153732-02,Monitoring mosquito eco-systems and vector-control strategies using a stand-off optical sensor.,"Monitoring mosquito ecosystems and vector-control strategies using a stand-off optical sensor. PI: B. Thomas â€Â"" NIH R21 Project Summary: Vector control strategies remain one of the most effective ways to protect human populations from the large number of mosquito borne diseases such as malaria, dengue fever, zika virus, or West Nile virus. Mosquito populations are generally monitored using physical traps, however this method suffers from many disadvantages. It requires long and expensive laboratory analysis by qualified personnel which drastically reduces the number of observed insects as well as time of trap deployment. Traps also provide a poor estimate of the actual population size or population density because the attractive range of traps is generally unknown and may change with weather conditions. These limitations are strong drawbacks in our ability to evaluate the effectiveness of various types of vector-control strategies (chemicals, biological, environmental modifications etc.). Inferior methods are not necessarily identified which ultimately contributes to the spread of infectious diseases. In this context, we argue that new methodologies to monitor insect population dynamics is key in the necessary effort to improve control program performance. A team from the New Jersey Institute of Technology in collaboration with the Hudson Mosquito Program seeks support to carry out a series of field experiments using a new optical sensor capable of identifying in real-time the family, species, and gender of mosquitoes in its field of view. The laser-based instrument is a dual-wavelength polarization-sensitive stand-off sensor. For each flying insect transiting through the infrared laser beams, the sensor can retrieve the optical properties of the wings and body of the insect as well as its wing beat frequency. Preliminary data from a laboratory prototype and numerical simulations indicate that the instrument, using a supervised machine learning classifier, can identify the species, gender, and gravidity of mosquitoes up to 300 m away. The instrument will be deployed in a high mosquito density area in New Jersey to continuously monitor the mosquito population over the whole season from April to October 2021. Continuous measurements will allow to identify a number of insects that is orders a magnitude higher than physical traps. As the probed volume of air is known, data analysis will provide the population density for each class of insects from which the population dynamics will be derived. In addition, the time and date of each insect transit allow to study the circadian rhythm, peak activities, and behavior as a function of atmospheric conditions measured by a weather station. In 2022, a similar experiment will be conducted at the same location while the Hudson Mosquito Program will conduct a vector control campaign targeting Culex and Aedes mosquitoes, both responsible for the spread of various infectious diseases. The impact of multiple applications of airborne pyrethroid insecticide on targeted and non-targeted insects will be evaluated by studying the mortality rates and population dynamics for each species. Both years, the data will be compared to physical traps on site, the current gold standard method, for further analysis and validation.",,2023,NEW JERSEY INSTITUTE OF TECHNOLOGY,151381,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P22265,5R01AI151166-03,Metabolic basis of mosquito-endosymbiont-virus interactions,"PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.",,2025,COLORADO STATE UNIVERSITY,579750,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22266,3R01AI151166-03S1,Metabolic basis of mosquito-endosymbiont-virus interactions,"PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.",,2022,COLORADO STATE UNIVERSITY,68481,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22267,1R56AI158674-01A1,Developing botanical-derived chemical tools for controlling mosquito vectors,"Project Summary: The yellow fever mosquito Aedes aegypti is the principal vector of several medically-important arboviruses that have recently emerged or re-emerged globally, such as chikungunya, dengue, and Zika. The mitigation of mosquito-borne diseases often relies on preventing mosquitoes from biting humans via the use of chemical control tools, such as insecticides and/or repellents. However, the emergence of insecticide resistance in mosquitoes has reduced the efficacy of the most widely used control agents (e.g., pyrethroids), resulting in a need to develop insecticides with novel modes of action. Moreover, only a few mosquito repellents are currently registered by the Environmental Protection Agency and recommended by the Centers for Disease Control. Limited knowledge on the modes of action of these repellents has hampered development and optimization of biorational mosquito repellents. Thus, chemical control tools with novel modes of action are needed to improve the management of mosquito vectors. With the support of an R21 grant, we discovered a drimane sesquiterpene (cinnamodial, CDIAL) from the bark of an endemic medicinal plant of Madagascar (Cinnamosma fragrans; family Canellaceae) that kills larval and adult female Ae. aegypti. The mode of toxic action of CDIAL in mosquitoes involves paralysis of visceral muscle associated with activation of Ca2+ channels, a unique mode of action compared to pyrethroids. Moreover, we found that CDIAL is a potent agonist of mosquito transient receptor potential ankyrin 1 (TRPA1) channels, an established mode of action for some mosquito repellents and antifeedants. The goal of the proposed R01 research is to develop novel CDIAL-based chemical tools for controlling mosquitoes with Ae. aegypti as our primary study species. In Aim 1, we will use natural products, medicinal chemistry, in vivo bioassays, and machine learning to develop quantitative structure-activity relationship (QSAR) models of the insecticidal and visceral muscle paralysis activities of CDIAL. These models will inform the iterative design of CDIAL derivatives that are at least 100-fold more potent than CDIAL as insecticides. In Aim 2, we will use in silico modeling and heterologous expression approaches to determine how CDIAL respectively binds to mosquito and human TRPA1 channels. This knowledge will inform the design and iterative QSAR-based optimization of CDIAL-based agonists that are at least 100-times more specific for mosquito over human TRPA1 channels and repel adult female mosquitoes. In addition, the in silico structural models of mosquito TRPA1 will be used to virtually screen a natural product library of over 400,000 compounds to discover novel mosquito-selective TRPA1 agonists that repel mosquitoes. Lead compounds from both Aims will be considered ‘candidates’ if they meet mammalian cytotoxicity benchmarks and are efficacious against multiple mosquito vectors (Anopheles gambiae, Culex quinquefasciatus). Collectively, results from both aims will facilitate development of next-generation chemical tools to control mosquito vectors.",,2024,OHIO STATE UNIVERSITY,648358,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2022 +P22268,5R21AI156078-02,Development of precision genome editing tools in Ae. albopictus for functional genetics and mosquito control technologies,"PROJECT SUMMARY The Asian tiger mosquito, Aedes albopictus, is an aggressive human-biting mosquito that is a competent vector of the dengue, chikungunya and Zika viruses as well as multiple native North American encephalitis viruses. The rapid spread of this mosquito from its native Asian range across the globe during the last 30 years and its well- established role as a primary vector of recent outbreaks of both dengue and chikungunya viruses represents an outstanding public health concern. The goal of this proposal is to produce and test a flexible and efficient precision genome editing system based on CRISPR-Cas9 in A. albopictus. We propose to produce multiple transgenic lines with stable germline expression of the Streptococcus pyogenes Cas9 protein (Cas9) driven by native A. albopictus promoters. Our rationale is that endogenously expressed Cas9 leads to higher editing rates, greater technical efficiency and dramatically decreased costs of genome editing relative to injection of exogenous sources of Cas9. This rationale is supported by our previous work in another closely related vector, Aedes aegypti, where the production of endogenous Cas9 lines not only improved functional genetic capabilities in this vector, but also provided the foundation for the development of genetic-based control technologies. In aim 1, we will produce transgenic lines with native A. albopictus promoter sequences driving Cas9 expression and fluorescent reporters. These lines will be rationally designed based on recent “omics” data in A. albopictus and our extensive work in another closely related vector. Lines will be tested that have different Cas9 promoters and insertion sites and lines with the most robust and stable Cas9 expression will be more extensively evaluated in single and multi-gene knockout studies. In aim 2, we will design and test small guide RNAs to target multiple genes of potential relevance to A. albopictus control including potential phenotypic markers for quality control and sex sorting applications, sex determinate genes and flight specific genes for sterile insect techniques and gene drive applications as well as essential genes of interest for gene drives. The research described in this proposal will advance A. albopictus genomics research by: (1) establishing a platform for rapid and efficient functional genetics and reverse-genetic screens of genes affecting a wide range of phenotypes relevant to disease transmission and vector control, and (2) completing a necessary first step to develop novel tools for vector control such as genetic sexing and gene drive.",,2023,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",197500,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector control strategies,2021 +P22270,1R13AI154985-01A1,International West Africa Symposium and Workshop on Infectious Diseases,"PROJECT SUMMARY West African countries suffer enormous impacts due to infectious diseases such as HIV, malaria, tuberculosis, Lassa, Ebola and Dengue. Despite the high relevance of basic and clinical research studies and the abundant availability of patient-derived samples and data, most of the sixteen West African nations lag behind developed nations and many other African nations in combating these epidemics. As a result, it is increasingly recognized that there is great value in increasing opportunities for West African scientists, particularly from countries such as Sierra Leone, which have been slower to progress as compared to others like Ghana and Nigeria. One goal is to have them participate more in basic and clinical research, both as independent researchers and as part of international consortia and collaborations. Until now, however, there has been little opportunity to bring the entire West African infectious disease research community together with leading researchers from other African nations and beyond. For this reason, we propose to hold the first International West Africa Symposium and Workshop on Infectious Diseases in Freetown, Sierra Leone. There are four specific objectives of this meeting. First, we aim to bring together the international infectious disease community in Sierra Leone to facilitate infectious disease research on a number of key pathogens highly relevant to the region. To accomplish this goal, we are planning a series of keynote and plenary speakers from many leading experts in the field from within Africa and around the world, along with a poster session, talks selected from poster abstracts and other activities including a site visit. Since the challenges in this field are daunting and will require collaborative efforts to solve, a second goal is to enhance interactions between diverse groups, such as academic basic science, epidemiological, clinical and translational science, as well as non-governmental and governmental institutions. To this end, we are specifically inviting participants representing these groups, with sessions to facilitate knowledge exchange and collaborations. A third objective is to bring hands-on training and workshops that our team is uniquely positioned to provide. To this end, there will be several days of workshops taught by experts and developed in close collaboration with team members on the ground in Sierra Leone, who understand the local needs. A fourth objective is to invest intellectually and financially in the future by supporting promising young trainees. The goal is to encourage trainees to be successful and stay in the field by providing intellectual support through discussions and mentorship with senior scientists, poster sessions, opportunities to speak, awards that recognize their achievements, and by providing financial support with competitive travel awards. The expected outcomes are increased collaborations between scientists working in different disciplines, retention of young scientists in the field, identification of new opportunities to mesh basic and clinical research, and exploration of new approaches for the study of infectious diseases and strategies to combat them.",,2023,"UNIVERSITY OF CALIFORNIA, SAN FRANCISCO",29559,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22273,75N93019C00062-P00016-9999-1,"B Cell Epitope Discovery and Mechanisms of Antibody Protection: Responses to Dengue 4, Powassan, Chikungunya, and Venezuelan Equine Encephalitis Viruses ","This contract supports the identification of human B cell epitopes derived from four viral pathogens; Dengue virus 4, Powassan virus, Chikungunya virus, and Venezuelan equine encephalitis virus, combined with basic studies to understand protective immunity mediated by antibodies, as well as pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. The primary goal of this contract is the delineation of B cell epitopes recognized by potently neutralizing or protective antibodies and evaluation of correlates of protection that can aid in the development of vaccines and therapeutics against select arthropod-transmitted viruses. The Contractor has chosen two flaviviruses (Dengue virus 4 and Powassan virus) and two alphaviruses (Chikungunya virus and Venezuelan equine encephalitis) for primary investigation of antibody responses to viral glycoprotein antigens. The Contractor will also evaluate protective antibodies that recognize the flavivirus nonstructural protein 1 (NS1) produced by West Nile and Zika viruses.",,2023,WASHINGTON UNIVERSITY,1665667,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22277,5R01AI151004-03,Precision guided SIT for the control of vector-borne disease,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases. Dengue alone causes 90 million infections per year globally and like many vector-borne diseases, currently there are no drugs or vaccines to treat or prevent these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. In recent years, novel vector population suppression technologies have been created (e.g. RIDL and Wolbachia based systems), but production of mosquitoes for these programs is labor intensive and is limited in scalability and distribution. In this study, we will use a functional genomic screening approach to identify key sex determinate, female essential (FE) and male fertility (MF) genes in the dengue vector, Ae. aegypti. These studies will improve our understanding of the biology of this important vector and it can be used to inform the design of new genetic population suppression methods to control this vector. After these genes are identified and characterized, we will incorporate them into the design of precision guided sterile insect technique (pgSIT) technologies in an attempt to overcome limitations in traditional SIT control strategies. Sterile insect technique (SIT) is the gold standard for insect population control but has many limitations. Our proposed technology aims to simultaneously knock-out FE and MF genes using a binary CRISPR/Cas9 system in the Ae. aegypti disease vector. One line will target one or more female essential FE genes and one or more MF genes and the other line will express a Cas9. When these two lines are crossed, they create sterile, male progeny that are ready for release into a population suppression program. To generate these lines, initially we will characterize >40 candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be determined over many generations to ensure population stability. The design and integration of these transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression systems, including the impact of transgene expression timing and transgene location on the long-term stability of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies. In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",461949,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P22278,5R25AI147391-03,Summer Institute in Statistics and Modeling in Infectious Diseases,"ABSTRACT The overall goal of the annual Summer Institute in Statistics and Modeling in Infectious Diseases (SISMID) at the University of Washington is to educate the next generation of researchers in a broad range of state-of-the-art quantitative methods for infectious disease research. Courses for skill development: SISMID is a collection of 16 2.5-day modules offered over 2.5 weeks in July on a variety of topics relevant to research education in statistics, modeling and computational methods applied to infectious diseases. Most participants take on average three modules per year. SISMID has been held each summer since 2009. This proposal requests funds for 2020-2024. The 2020 SISMID proposes to offer the following: 1. Probability and Statistical Inference; 2. Mathematical Models of Infectious Diseases; 3. Introduction to R; 4. Causal Inference; 5. Evolutionary Dynamics and Molecular Epidemiology of Viruses; 6. Stochastic Epidemic Models with Inference; 7. Markov chain Monte Carlo I; 8. Microbiome Data Analysis; 9. Pathogen Evolution, Selection, and Immunity; 10. Simulation-based Inference for Epidemiologic Dynamics; 11. Statistics and Modeling with Novel Data Streams; 12. Infectious Diseases, Immunology, Within Host Models; 13. Markov chain Monte Carlo II for Infectious Diseases; 14. Spatial Statistics in Epidemiology and Public Health; 15. Contact Network Epidemiology: 16. Reconstructing Transmission with Genomic Data. The instructors are drawn from the University of Washington and other academic institutions in the USA and Europe, and industry. Instructor mentors will be assigned to recipients of support through this grant and put into email contact before SISMID. They will meet together during SISMID. Research experiences will include teams working on ongoing projects and using innovative methods for reproducible research. This NIAID Research Education Program (R25) will allow us to provide graduate students and postdoctoral fellows approximately 350 modules per year without charge and 100 partial travel awards.",,2025,UNIVERSITY OF WASHINGTON,330891,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P22280,5R01AI148551-03,Mosquito hydration status as a mechanism that alters pre-feeding host interactions and post-feeding physiology,"Project summary Insects are extremely prone to dehydration, where individuals may succumb after exposure to only a few hours of dry conditions. Mosquitoes are highly susceptible to desiccation due to high water loss rates, especially when temperatures are high, relative humidity is low, and drinking water is lacking. Importantly, if dehydrated mosquitoes move to more humid areas, dehydration-induced phenotypes can last for many hours. Recent studies have examined mosquito development and other specific topic areas under dry season conditions, but no integrative studies have examined the role of dehydration bouts on mosquito behavior, physiology, and potential for disease transmission. For most insects, exposure to xeric periods prompts their retreat into favorable microhabitats until conditions improve, which could take hours or weeks. Our preliminary studies indicate that activity and blood feeding in mosquitoes increase by three- to four-fold following sub-lethal dehydration, but the potential mechanisms and impact of this phenotype are unknown. The focus of this proposal will be examining the effect that dehydration has on mosquito biology, specifically how desiccation stress alters general mosquito biology, host choice, host-pathogen interactions, and disease transmission. The primary study organism will be the northern house mosquito, Culex pipiens, a vector for West Nile virus, with comparative studies to mosquito species to Aedes aegypti. These studies are supported by 1) experimental designs that can discern the effects between only exposure to dry conditions and direct mosquito dehydration (= organismal water loss), 2) preliminary studies on CRISPR-Cas9 lines of chemosensory proteins which show altered water attraction, 3) shifts in blood feeding and diversion of blood to the crop, 4) increased retention of the bloodmeal in dehydrated mosquitoes when compared to hydrated counterparts, 5) differential expression of immune genes following a bloodmeal if mosquitoes are dehydrated before host feeding, and 6) field-based mesocosm experiments that indicate dehydrated mosquitoes are more prone to blood feeding. This study has four specific aims: Specific Aim 1. Influence of dehydration on basic biological parameters before and after blood feeding. Specific Aim 2. Examine aspects underlying behavioral modifications of mosquitoes following dehydration stress. Specific Aim 3. Impact of dehydration on viral retention and transmission. Specific Aim 4. Field-based observations and mathematical modeling of disease transmission changes due to dehydration exposure. Overall goal accomplished by the completion of these proposed studies: These proposed studies will be transformative by providing the first integrative experiments that examine the effects of dehydration bouts on the dynamics between mosquito physiology, behavior, and pathogen transmission.",,2025,UNIVERSITY OF CINCINNATI,402085,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector biology | Vector control strategies | Disease surveillance & mapping,2020 +P22281,5R01HL153073-03,Transfusion-related immunomodulation influences infectious disease outcomes,"Project Summary/Abstract Transmission of acute viral infections through blood transfusion during large epidemics is a serious public health issue, particularly for newly emerging infections for which no sensitive FDA-approved tests are available. Arboviruses can be serious acute infections leading to serious long-term complications, and are noted for their massive epidemic, as recently demonstrated with first chikungunya virus (CHIKV) and then Zika virus. Despite possessing many of the characteristics required for blood transfusion transmission (TT), such as high loads of infectious virus in blood and the ability to infect via intravenous inoculation, there have never been any CHIKV TT events reported. This is despite large-scale epidemics where up to 2% of blood donations have been found to be RNA reactive. We have preliminary data supporting the fact that CHIKV can be transfusion-transmitted in mice, and that transfusion of RBC attenuated CHIKV pathogenesis. The central hypothesis behind this study is that TT does occur, however a number of factors drive infection towards being asymptomatic or mild. Further, immune modulation during transmission, in this case via the blood transfusion itself, leads to an attenuation of disease. Specifically, we and others have demonstrated a number of innate immune factors are both modulated by transfusion and able to alter CHIKV outcomes. These include innate lymphoid cells and regulatory T cells and the cytokines both upstream and downstream of their stimulation. This study will use a murine model of CHIKV pathogenesis to investigate these findings further. Additionally, it will mimic blood transfusions, TT of CHIKV, and study immune parameters and disease outcomes. Beyond understanding the interplay between pathogenesis and blood transfusion, these studies will have a wider impact on acute viral infections in general. It is likely that similar immune factors can have dramatic effects on viral replication and/or pathogenesis, and thus a deeper understanding of how these mechanisms are mediated will allow better planning for screening efforts and potentially even interventions during serious epidemics. This will allow improved capabilities and decision making in responding rapidly to a new viral threat to blood safety and availability.",,2024,VITALANT,615838,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P22282,5U01AI151788-03,American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES),"ABSTRACT Recent pandemics of human pathogens have revealed the limitations of current surveillance systems. The sequential arboviral epidemics in the Americas showed how outbreak detection can be delayed and opportunities missed to collect well-characterized specimens and data for surveillance, basic science, clinical research, and development of vaccines and new diagnostics. In response, we have assembled a consortium of world-renowned investigators in arbovirology, epidemiology, immunology, viral diagnostics, phylogenetics, and clinical research, while leveraging research infrastructure and expertise in long-term cohort and hospital-based studies. This has resulted from 3 decades of collaborative international research, with over 200 joint publications, and extensive experience in preparing for and responding to outbreaks working closely with local and international health authorities and NIAID. With key sites in Asia and the Americas, we will use innovative molecular and serological methods to identify emerging pathogens and to address fundamental questions in dengue and other arboviral epidemiology and test viral, host and environmental determinants of differences between sites along a gradient of urbanicity. Our overarching goal is to develop an interconnected, harmonized network of clinical and laboratory sites to strengthen research programs, compare disease epidemiology and severity in different regions, develop and implement cutting-edge diagnostic methods, and respond efficiently and effectively to outbreaks. Standardized hospital studies and community-based cohorts in Ecuador, Nicaragua and Sri Lanka will characterize and compare human arboviral illnesses across urban, peri-urban and rural sites and develop sustainable infrastructure to rapidly respond to epidemics together with Ministries of Health, comple- mented by outbreak investigation, surveillance of non-human primates, and vector incrimination. We will imple- ment standardized plans for study administration, data and clinical management, and statistical analysis across sites, supported by an extensive on-site training program. Aim 1 will establish standard and novel multiplex assays at each site for surveillance, diagnosis and research of arboviruses and other pathogens. Aim 2 com- pares dengue/arbovirus epidemiology and transmission in cohort studies located in ecologically distinct regions over a continuum of urbanicity. In Aim 3, we will characterize complete viral genome sequences for comparative studies of arboviral phylogenetics, phylogeography and molecular epidemiology. Aim 4 consists of surveillance, identification, and characterization of novel and unrecognized human pathogens from severe hospitalized cases, unexpected outbreaks, vectors and non-human primates. Molecular and serological assays will be developed for newly identified pathogens and quickly implemented across study sites to characterize the epidemiology and clinical manifestations and will be made available to the EIDRC network. In sum, our A2CARES Consortium will provide valuable new tools and knowledge and 3 interconnected centers in Latin America and South Asia that will be able to respond to outbreaks and to study emerging and endemic infectious diseases far into the future.",,2025,UNIVERSITY OF CALIFORNIA BERKELEY,1554254,Viruses,Not applicable,Not Applicable,Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease transmission dynamics | Disease surveillance & mapping",2020 +P22284,5R01AI150672-02,Dengue virus mRNA lipid nanoparticle vaccine,"Nearly 400 million people are infected with dengue virus (DENV) each year through the bite of infected mosquitos concentrated in the tropical and subtropical regions of the world. Symptoms can range from febrile illness to severe dengue that manifests as plasma leakage, sudden loss of blood pressure, organ failure, and shock that can ultimately lead to death. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross- reactive, poorly-neutralizing epitopes lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). Additionally, DENV immunity has been implicated in increased susceptibility to Zika virus through ADE. Currently there are no available therapeutics to combat DENV disease. Dengvaxia, the only licensed DENV vaccine, was found to increase hospitalization rates in naïve populations, and thus is not recommended for a large portion of at-risk individuals. There is an urgent need for a safe and efficacious vaccine that elicits a robust, balanced, neutralizing response to all four DENV serotypes. We propose to develop a novel DENV vaccine utilizing an emergent platform: mRNA encoding for viral proteins encapsidated in a lipid nanoparticle (LNP). mRNA-LNP vaccines elicit robust humoral and cell-mediated immune responses in a safe, non-infectious platform. Additionally, we can direct the host immune response towards neutralizing epitopes by mutating the mRNA encoding for the viral protein. We hypothesize that a sequence-engineered tetravalent mRNA-LNP vaccine will induce a balanced, protective immune response against all four serotypes of dengue without the potential of causing immune enhancement and ADE. In Aim 1 of this study we will generate and optimize mRNA constructs encoding for the pre-membrane and envelope viral glycoproteins for all four serotypes of DENV. We will mutate the poorly-neutralizing, cross-reactive epitopes that drive ADE. In Aim 2 we will characterize the immune response to the vaccines in a mouse model. In addition to quantifying humoral and cellular immune responses, we will also measure the immune enhancement capacity of all vaccines. In Aim 3, we will evaluate vaccine efficacy and safety in susceptible mouse models, by challenging vaccinated mice with different DENV serotypes to monitor protection and ADE. We will also determine mechanism of protection via adoptive transfer experiments. Through this study, we will identify DENV vaccines that demonstrate broad protection and lack of immune enhancement for further evaluation as candidate human vaccines.",,2025,UNIVERSITY OF ILLINOIS AT CHICAGO,583700,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +P22285,1F32AI161786-01A1,Host genetic determinants of neuroinvasive flavivirus pathogenesis,"PROJECT SUMMARY Powassan virus (POWV) is an emerging tick-borne neuroinvasive flavivirus. Similar to mosquito-borne flaviviruses such as West Nile virus and Japanese encephalitis virus, POWV causes neuroinvasive disease, including encephalitis, meningitis, paralysis, and death. While the majority of flavivirus infections result in asymptomatic infection, a subset of symptomatic flavivirus infections progress to neuroinvasive disease, although the factors influencing susceptibility to severe disease are not fully understood and little is known about the pathogenic mechanisms of POWV. We hypothesize that variation in host antiviral response genes contributes to differential disease outcome following flavivirus infection. We propose to use Collaborative Cross (CC) mice to characterize features of POWV pathogenesis and identify host genes that contribute to POWV susceptibility. The CC is a mouse genetic reference population of recombinant inbred mice generated by crossing eight founder lines that represent three wild-derived and five classical laboratory mouse lines. The CC captures the genetic diversity of laboratory mice in a reproducible manner, since each of the ~80 lines has a known and fixed genome, providing a valuable tool for mapping complex traits. In preliminary studies, we infected a panel of Oas1b-null CC mouse lines with POWV and observed a range of susceptibility phenotypes, suggesting there are host factors other than the well-characterized flavivirus restriction factor Oas1b that modulate POWV pathogenesis in mice. We identified multiple highly susceptible lines (100% lethality), including CC071, and a single resistant line (0% lethality), CC045. Building on this preliminary data, we propose to i) determine viral and immunologic features of POWV pathogenesis in susceptible and resistant CC lines, and ii) map Quantitative Trait Loci (QTL) associated with POWV pathogenesis using F2 progeny of susceptible and resistant lines. In Aim 1, we will evaluate viral loads and infiltrating leukocytes in the CNS following POWV infection, characterize POWV replication in primary cells, and assess blood-brain barrier permeability, using susceptible (CC071) and resistant (CC045) CC lines. In Aim 2, we will evaluate POWV lethality, viral loads, and infiltrating leukocytes in the CNS of F2 mice and map QTL associated with these phenotypes to identify host genetic elements that contribute to POWV susceptibility. The proposed studies will further our understanding of flavivirus neuroinvasive disease through identification of host genetic factors that modulate POWV susceptibility in mice and provide insights into factors that impact neuroinvasive flaviviruses more broadly. The proposed training plan will focus on building a foundation in quantitative genetics techniques to investigate viral and immunologic mechanisms of POWV pathogenesis, and will prepare me for a career as an independent investigator using quantitative genetics techniques to study infectious diseases.",,2025,UNIV OF NORTH CAROLINA CHAPEL HILL,67582,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2022 +P22286,1R21AI167849-01,How can mosquitoes develop and reproduce in the complete absence of juvenile hormone?,"PROJECT SUMMARY Recent dramatic increases in the incidence of mosquito-borne diseases, like Malaria, Zika, Chikungunya and Dengue Fever, and the wide-spread resistance of mosquitoes to insecticides emphasizes the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on continued basic research on the biology of mosquitoes. Juvenile hormone (JH), an epoxidated sesquiterpenoid, is an essential regulator of major developmental and life history events in insects. Insects and crustaceans originated from aquatic pancrustacean ancestors that invaded terrestrial ecosystems over 450 million years ago. The Methoprene-tolerant (Met) protein is the intracellular receptor for insect JHs. The ability of Met to respond to MF, the “crustacean JH”, suggests that the role of Met in sesquiterpenoid signaling precedes the evolutionary separation of the hexapoda from the crustacean lineages. To address the evolutionary and biological significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, the methyl transferase (JHAMT) and the P450 epoxidase CYP15 (EPOX). jhamt-/- larvae lacking both MF and JH died at the onset of metamorphosis. While epox-/- mutants, which synthesized MF but no JH completed the entire life cycle. While epox-/- adults are fertile, the reproductive performance of both sexes is dramatically reduced. Using these two lines of null mutant mosquitoes, we will investigate how in the absence of JH, MF is sufficient to complete adult development. Our hypothesis is MF is able to properly activate the gene networks that control mosquito larval development and metamorphosis. Additionally, we will investigate the reproductive fitness cost in JH null females. We expect to recognize the molecular mechanism underlying the differences in JH signaling in our three model lines (jhamt-/-, epox-/- and WT). Our two null mutant mosquito lines provide a unique opportunity to explore the role of non-epoxidated versus epoxidated JHs in the development and reproduction of insects. Completing the proposed research could lead to the identification of targets for designing new, specific and affordable strategies suitable for mosquito control.",,2023,FLORIDA INTERNATIONAL UNIVERSITY,221250,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22287,5F31AI154824-02,Scalable Inference in Statistical Models of Viral Evolution and Human Health,"Project Summary / Abstract Despite global public health advances, viruses remain a major threat to human health both in the United States and internationally. Recent and continuing outbreaks of SARS-CoV-2, Ebola, Zika, Lassa fever, and Chikungunya, as well as persistent epidemics such as HIV have emphasized the need to understand viral evolution and virus-host interactions during epidemics. Phylogenetic statistical models of viral evolution offer a powerful tool for studying the interplay between viral genetics and environmental or host factors. However, current phylogenetic models are often too inï¬Â'exible to realistically model these relationships, and those that do are computationally intractable for even moderately sized data sets. This project aims to develop new statistical models that are both ï¬Â'exible enough to model complex biological relationships and scalable to large data sets of viral and host traits. The first aim is to develop more efficient and less biased statistical methods for estimating the heritability of viral phenotypes (e.g. viral load, host CD4 T-cell count, replicative capacity). Current statistical practices typically produced biased heritability estimates and are intractable for large data sets. This project seeks to extend state-of-the-art inference techniques to model the heritability of viral pheno- types (enabling both unbiased and efficient inference) and to apply these new methods to better estimate the heritability of viral load in HIV-1. The second aim seeks to develop statistical methods for studying complex, high-dimensional viral phenotypes such as infection severity which cannot be captured with a single measure- ment. These phenotypes are difficult to quantify due to their inherent complexity, confounding rigorous efforts at, say, identifying unusually virulent viral clades. While phylogenetic factor analysis enables identification and quantification of high-dimensional phenotypes, it scales poorly to large data sets. We propose new inference techniques that address these scalability problems and allow previously intractable analyses. We plan to apply these new methods to study patterns of virulence in Ebola and Lassa fever and to identify unusually virulent viral strains. Additionally, these methods are well suited to identifying epistatic interactions between viral mu- tations and phenotypes of interest, and we plan to explore these interactions in HIV, Zika, and Chikungunya viruses. The third aim is to develop new statistical models specifically designed to predict outcomes of viral infections from viral sequence data. To accommodate the necessary ï¬Â'exibility required by these models, we develop new inference strategies that are both highly generalizable (i.e. they do not rely on strict assumptions in existing models) and computationally efficient. Strong predictive performance would enable researchers or clinicians to predict clinically relevant outcomes using viral sequences, which could help inform treatment. We will evaluate these methods using the Ebola and Lassa fever data from mentioned above.",,2022,UNIVERSITY OF CALIFORNIA LOS ANGELES,25832,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae | Flaviviridae,,,,,,,,,Lassa fever | Ebola virus disease | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P22290,1R41AI162366-01A1,Developing Vertebrate-Specific Replication-Defective Dengue Virus as Novel Single-CycleDengue Vaccine Candidate,"Developing Vertebrate-Specific Replication-Defective Dengue Virus as a Novel Single-Cycle Dengue Vaccine Candidate Abstract With an estimated minimum of 390 million dengue virus (DENV) infections per year, the DENV epidemic was listed as one of the world's top 10 public health threats by WHO in 2019. At present, there is no specific treatment. A universal vaccine is urgently needed. DENV vaccine development's unique challenge is that a dengue vaccine must induce long-term protection against all four serotypes simultaneously. Historically, tetravalent live attenuated viral vaccines have shown that it is difficult to achieve balanced immunity to all four serotypes. Also, inactivated virus vaccines can't confer long-term immunity to prevent potential antibody-dependent enhancement (ADE). Mindful of these obstacles, we have investigated single-cycle, pseudoinfectious DENVs as vaccine candidates to induce balanced long-term immunity against all four serotypes. A significant impediment to this approach is that replicating pseudoinfecious DENVs usually require complicated and low-efficient packaging cells, making the scale-up production difficult and costly. Thus, towards the overall goal of developing a safe, effective, and affordable DENV vaccine, we converted dual-tropic DENVs into artificial insect-specific viruses to overcome the dependence on packaging cells to produce a single-cycle virus vaccine. These vertebrate-specific replication-defective DENVs (VSRD-DENV) were generated by optimizing the furin cleavage site in viral pre-membrane protein (prM). Preliminary animal experiments with VSRD-DENV1 and VSRD-DENV2 demonstrated that the VSRD-DENVs induced robust protective immunity with inherent high safety levels in mice. Based on these highly promising preliminary results and considering the urgent need for an effective dengue vaccine, Tengen Biomedical Co. and Howard University have teamed up to accelerate the evaluation of the VSRD-DENVs-based dengue vaccine. To achieve this goal, we propose to generate and characterize VSRD-DENV3 and VSRD-DENV4 vaccine candidate viruses. We will then perform a comprehensive analysis of the immunogenicity and protective efficacy of tetravalent VSRD-DENVs in a sensitive AG129 mouse model. Successful completion of these proposed studies will enable the dengue vaccine candidate into non-human primate testing and establish a platform for developing vaccines for other important flaviviruses.",,2023,TENGEN BIOMEDICAL CO.,298530,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity | Vaccine design and administration",2022 +P22291,5R01AI165560-02,Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats,"Project Summary Each year, approximately 400 million people are infected with an arboviral disease from the bite of an Aedes spp mosquito. Aedes spp. mosquitoes are a leading public health threat due to their high competency to vector multiple pathogens, their preference to bite humans, and their ability to adapt to new domestic environments. In the US, reintroduction and establishment of Aedes aegypti and Aedes albopictus mosquito populations has resulted in local epidemics of Zika, dengue and chikungunya in the past decade. Unfortunately, mosquito control programs in the US generally operate with limited budgets, forcing the majority of insecticide spraying to be conducted in reaction to population exposure instead of targeted prevention, which has also contributed to considerable growth of insecticide resistant populations, yielding a widening gap of infrastructure vulnerability. Our current proposal aims to leverage existing technologies from non-health disciplines to advance mosquito detection and abatement. We propose to validate the use of technology-driven mosquito traps that allow for high- throughput identification and counting of Aedes mosquitos at various life stages to inform decision making when selecting areas for insecticide spraying and abatement. Additionally, we propose to develop rigorous remote sensing workflows for identification of neighborhood-level Aedes abundance risk and rapid detection of individual Aedes mosquito breeding habitats on a household-level. This innovative proposal uses multi-year and real-world mosquito data from two different metropolitan areas to statistically adjust for variances in geographic ecologies, urban microclimates, seasonal climate patterns, and annual weather events. Our study will result in low-cost tools immediately ready for broad distribution and integration by vector control agencies nationally. The outcomes of our study have promise to directly impact vector control agency’s decision-making processes for mosquito trapping site selection, inform preventative abetment protocols, and shorten the time required for mosquito collection and identification. Further, integration of our proposed technology traps and informed site selection maps will increase overall collection volumes while preserving scarce resources for local vector control agencies. This proposal has the potential to create a paradigm shift in how we approach vector control globally, with a targeted intervention resulting in significant economic, environmental, and clinical benefits.",,2026,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,749701,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P22292,5R01AI155959-02,"Sample-to-Answer, Rapid, Multiplexed and PCR-Free Diagnostics of Arboviral Diseases in Resource Limited Settings","Arthropod-borne viruses (arboviruses) comprise many of the most important ‘emerging pathogens’ due to their geographic spread and their increasing impact on vulnerable human populations. There is urgent need for easy-to- operate and rapidly deployable diagnostic tools that can handle blood samples in a closed sample-to-answer manner. Here, we propose to develop a novel diagnostic technology that can detect viral antigens in an inexpensive, ultrasensitive, specific, and multiplexed manner. We will develop our novel approach into standalone tool with a detection capability at attomolar sensitivities (comparable to nucleic acid amplification tests) to diagnose arboviral infections with minimal user interference. The integrated diagnostic platform will utilize a novel surrogate approach, microfluidic integration, and a multiplexed detection scheme with the capacity to distinguish arboviral infections. The system will be designed to initiate diagnosis from serum/plasma/blood and provide a sample-to-answer diagnostic within less than 35 minutes using less than 100 Ã'µL blood samples at a cost of $2 per test. Collaborative work proposed for this NIH/NIAID R01 Grant involves integration of nanophotonic engineering (Yanik Group), molecular virology (Pinsky Group), and infectious diseases epidemiology (LaBeaud Group) to build and field-test our novel point-of-care viral diagnostic platform with Windward Islands Research and Education Foundation (WINDREF) and St. George’s University teams (Macpherson, Waechter and Noel Groups). Preliminary validation tests with patient samples will be initially performed at Stanford Medical Facility in collaboration with LaBeaud and Pinsky groups. Subsequently, three prototypes will be transferred to Grenada for field-testing initially at central laboratories then to resource-poor settings in small towns. Yanik group will provide the necessary expertise for integration of molecular and nanoengineering components and demonstration of a practical prototype as well as evaluating the application of prototype(s) developed under this proposal with patient samples (LaBeaud and Pinsky Groups). System will be iteratively optimized and a rugged platform suitable for field settings will be developed.",,2025,UNIVERSITY OF CALIFORNIA SANTA CRUZ,756783,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P22294,1R03NS130489-01,A vertebrate model of viral and hereditary microcephaly,"PROJECT SUMMARY/ABSTRACT Microcephaly, in which head and brain development are severely inhibited, can result in extreme intellectual disability. Microcephaly has many different causes, including gene mutation, pathogen infection and chemical exposure. While the causes of microcephaly may be broad, there may be shared molecular mechanisms involved. Recently published results show how Zika virus non-structural protein 4A (NS4A) inhibits brain development in fruit flies by inhibiting the same ANKLE2 protein whose function is disrupted by gene mutation in a hereditary form of microcephaly. This suggests that there may be key similarities in the molecular mechanisms contributing to a viral and hereditary form of microcephaly. Studying these molecular similarities in vertebrate models is essential to understanding disease in humans since vertebrates have different brain structure and genes that regulate brain development. However, the tools to study this, namely a strong vertebrate model system, do not exist. The primary goal of the proposed project is to fill these major gaps in knowledge by developing a vertebrate model of viral and hereditary microcephaly acting through the ANKLE2 pathway. For the hereditary model, ankle2 will be mutated using CRISPR/Cas9 genome editing. For the viral model, Zika virus NS4A protein will be expressed using Tol2 transgenesis. Defects in development, including various externally measured morphology metrics, brain size, structure and cellular defects in proliferation and survival will be assayed using anatomical measurement and immunofluorescence microscopy. When completed, this new model system will lay the foundation for a molecular and cellular level understanding of ANKLE2 function during vertebrate brain development and how it is disrupted by gene mutation and viral infection. In the long-term, it will enable high- throughput screening of chemical sensitizers and inhibitors of microcephaly, allow the exploration vertebrate- specific mechanisms of brain development in vivo, and behavioral studies.",,2024,UNIVERSITY OF CALIFORNIA AT DAVIS,159875,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models",2022 +P22295,1R03AI167042-01,Phenotypic characterization of T’Ho virus and the development of tools for its serologic diagnosis,"PROJECT SUMMARY T’Ho virus is a poorly characterized flavivirus recently discovered in Culex quinquefasciatus mosquitoes in the Yucatan Peninsula of Mexico. The genome of T’Ho virus was fully sequenced but an isolate was not recovered by suckling mouse brain inoculation or by virus isolation in vertebrate or mosquito cell cultures. Genome sequence alignments revealed that the closest known relatives of T’Ho virus are mosquito-transmitted flaviviruses associated with life-threatening human disease. Rocio virus, a BSL-3 pathogen, is the closest known relative, followed by Ilhéus, St. Louis encephalitis, Japanese encephalitis and West Nile viruses. Because T’Ho virus is most closely related to known human pathogens, it too could be a cause of human disease. Clinical and serological studies need to be performed to investigate this issue. There is also an important need to perform in vivo experimental infections to identify competent vertebrate host and vector species. The ability to perform these experiments is severely restricted by the unavailability of an isolate. To address this issue, recombinant technology will be used to create infectious viruses that can be used for T’Ho virus research and diagnosis. The first objective is to generate recombinant T’Ho virus and characterize its in vitro host range and replication kinetics. Based on its close phylogenetic relationship with flaviviruses that cycle between mosquitoes and vertebrate hosts, it is hypothesized that T’Ho virus replicates in both mosquito and vertebrate cells. The second objective is to create a chimeric virus that can be used in BSL-2 laboratories for the detection of neutralizing antibodies to T’Ho virus. Because T’Ho virus is closely related to several BSL-3 pathogens, it could eventually be classified as a BSL-3 agent. However, many arbovirus laboratories, particularly those in Latin America, lack BSL-3 facilities. Therefore, a chimeric virus will be generated by substituting the major structural protein genes of Zika virus, a BSL-2 pathogen, with the corresponding region of T’Ho virus, producing a virus that can be used in BSL-2 laboratories. It is hypothesized that the aforementioned genetic exchange is functionally compatible and will generate a chimeric virus that forms plaques in vertebrate cell monolayers. The proposed studies provide the foundation for many future experiments. Vertebrate animals and mosquitoes can be experimentally inoculated with the recombinant virus to identify competent reservoir hosts and vectors of T’Ho virus, providing insight into its transmission cycle. The recombinant virus will allow researchers to monitor humans and vertebrate animals in Mexico and elsewhere in the Americas for antibodies to T’Ho virus by plaque reduction neutralization test (PRNT). The PRNT is the gold- standard serologic technique for the diagnosis of flavivirus infections and it requires live virus. The chimeric virus can be used when BSL-3 facilities are unavailable. Flaviviruses are known for their serologic cross-reactivity; thus, it is likely that antibodies to T’Ho virus can bind to and neutralize other flaviviruses. This raises the possibility that some human and vertebrate animals previously tested by PRNT in serologic investigations in Latin America contained antibodies to T’Ho virus but were misdiagnosed. It is important that infectious T’Ho virus is available so it can be included in PRNTs and considered in the differential diagnosis.",,2024,IOWA STATE UNIVERSITY,76500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22296,1R21AI171913-01,Human sweat taste and contact-guided behavior in Aedes aegypti,"PROJECT SUMMARY Mosquitoes are responsible for transmitting disease to hundreds of millions of people each year. Behavior- modification strategies have been major tools in surveillance and control efforts. A lot of attention has been devoted to elucidating and manipulating detection of thermosensory and olfactory cues that drive host-seeking behavior. However, a critical gap exists in our understanding of contact chemosensation in mosquito-host interactions, despite the fact that biting and blood feeding behaviors are crucial factors in driving disease transmission. After a mosquito has found a host, she lands on and examines the skin surface, and probes it with her stylets before initiating a blood meal. It is well known that the human skin surface is replete with chemicals, including those found in sweat. An understanding of whether human sweat cues can be sensed by the mosquito taste system, and if so, whether these cues activate behaviors that precede initiation of blood meals, would provide a valuable entry point for developing new behavior-modifying tools for surveillance and control. Our model of choice is Ae. aegypti, a vector of Dengue, Chikungunya, and Zika viruses, which is responsible for an enormous worldwide burden on human health, and is now also established in some regions of the United States. We propose to explore the hypothesis that soluble compounds present on human skin are sensed by the mosquito taste system and activate close-range behaviors that precede blood feeding. We focus on human sweat components, which include free amino acids in addition to salts, acids and ammonia derivatives. The premise behind our hypothesis is supported by our pilot data, in which we find that an artificial sweat mixture as well as certain individual amino acids and salt can activate taste neurons in female mosquitoes. Further, mixtures presented on a filter paper target can stimulate interaction and probing attempts in mated females. The specific goals of our proposal will be accomplished via two aims. In AIM 1, we will create a map of taste responsivity of human sweat components and mixtures in the female Aedes aegypti mosquito. We will determine if these stimuli promote residency or pre-feeding behaviors such as labellating and probing using independent population-based and single-female behavior assays. In AIM 2, we will evaluate whether cellular and behavioral responses to human sweat tastants are altered by knocking out selected taste receptors/co- receptors using CRISPR/Cas9-mediated genome editing. The results of the proposed studies will provide important molecular and neurophysiological insights into mosquito taste-guided behaviors elicited by compounds found in human sweat.",,2024,UNIVERSITY OF CALIFORNIA RIVERSIDE,233250,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P22297,5F32AI150123-03,Flavivirus cellular tropisms driving dissemination and transmission in mosquito vectors,"Project Summary/Abstract The research objectives of this fellowship are to determine the cellular tropisms of three mosquito-borne flaviviruses of public health importance â€Â"" Zika virus, dengue virus and yellow fever virus â€Â"" within their Aedes aegypti vectors and to define the roles of specific cell populations in viral dissemination and transmission. The aims are to 1) identify the specific cell populations critical for viral dissemination from the midgut to the salivary glands, and 2) define the impact of specific tissue tropisms on mosquito feeding behavior and viral transmission. Aim 1 will be accomplished by generating microRNA (miRNA) expression profiles for midgut, hemocyte and neuronal cell populations and selecting miRNAs that are highly differentially expressed in each population. We will confirm infection of cells expressing these miRNAs and generate cell-specific, miRNA-restricted viruses containing target sequences for cell-specific miRNAs to probe the roles of each cell type in viral dissemination. Aim 2 will be accomplished by using miRNA-restricted viruses to determine the effect of neuronal cell and salivary gland infection on mosquito feeding behaviors and subsequent transmission of the virus by observing infected mosquitoes feeding on mice and testing mice for the presence of virus. The data and tools produced by this work could aid the development of transmission control strategies that target viral replication in specific cell populations within the vector. Research and postdoctoral training activities will be undertaken at both Colorado State University and the Centers for Disease Control and Prevention in Fort Collins, CO. The sponsor and co- sponsor laboratories have complimentary research interests and facilities that will promote the success of this project. In addition to research, the training plan includes completion of coursework in next generation sequencing experiment and analysis, grant writing, and responsible conduct of research; participation in supervisory training; and attendance at various workshops, seminars and conferences to improve writing, presentation and career building skills.",,2023,COLORADO STATE UNIVERSITY,72302,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22298,5F31AI152453-02,Identification of Flavivirus Nucleocapsid Core-Envelope Glycoprotein Interactions,"Project Summary/Abstract Flaviviruses (a family of over 90 known viruses, including Zika, dengue and West Nile) are significant human pathogens affecting 3.1 billion people annually, and most of these enveloped viruses do not have any viable vaccines or antivirals capable of combating their spread. The primary objective of current flavivirus antiviral design is to disrupt specific mechanisms in the flavivirus life cycle that are key for virus survival, including virus attachment to the host cell, viral endocytosis, genome uncoating, genome replication, and virus maturation through the Golgi. These potentially druggable mechanisms have been explored in great detail both within our lab and elsewhere. However, little is known about the assembly mechanisms that drive infectious virus particle formation. Because of the high structural homology among all flaviviruses, the identification of assembly mechanisms will provide ubiquitous targets for therapeutic intervention in virus proliferation. In other enveloped virus systems, assembly depends on the interaction of virus core proteins with lipid membranes or membrane bound glycoproteins to produce infectious virus particles. Exploration via single particle Cryo-EM reconstruction has shown that the nucleocapsid core (NC) of immature Zika virus, is found in close proximity with the envelope glycoproteins on the inner side of the virus’s lipid bilayer. Due to this close proximity, I hypothesized that the NC interacts with the envelope glycoproteins during virus assembly. I further hypothesized and that these interactions occur between the capsid protein (CP) and transmembrane helices of the precursor membrane (prM) protein and the envelope (E) protein while the particle is in the immature state. Since no information currently exists on virus assembly relying on CP-prM/E interactions, these interactions have the potential to be exploited as new drug targets capable of inhibiting the proliferation of flaviviruses. To this end, I am investigating two independent strategies to validate the hypothesized NC-prM/E interactions using dengue virus serotype 2 (DENV2) as a model system. The Kuhn lab is particularly adept in mutagenesis studies using DENV2, which is why the decision was made to use this virus as our model system instead of Zika. Firstly, amino acids within the prM/E transmembrane helices that were posited to be key in the assembly process of DENV2 and other flaviviruses have been or will be mutated to investigate their role in promoting particle assembly. Secondly, the ability of the DENV2 prM and E transmembrane helices to interact with CP is being examined through the use of reconstituted prM and E proteins within SMA lipid nanoparticles. Due to the high similarity of all flaviviruses, the techniques, results and mechanisms identified in this study can be applied to other flaviviruses. Combining these essential experimental studies with the proposed training skills and collaborative opportunities for effective scientific communication through writing, speaking and mentoring will prepare me well for a future in biomedical research.",,2022,PURDUE UNIVERSITY,37658,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22299,5R01AI151029-03,Next Generation Resolution of Antiviral Gene Networks,"SUMMARY As the primary mediators of the innate response to viral infection, type I interferons (IFN-I) establish an antiviral state in both infected and uninfected bystander cells through the induction of several hundreds of interferon stimulated genes (ISGs). The mechanisms by which the coordinated activities of these ISGs confer resistance to diverse viruses, and the regulatory circuits that modulate their expression remain poorly understood. Working with unique samples from individuals with hereditary syndromes of dysregulated IFN-I responsiveness, we have identified a collection of thirty ISGs that confer resistance to diverse viruses (increased protection against RNA and DNA viruses with both high and low pathogenic burden). We have also uncovered previously unappreciated negative feedback mechanisms of IFN-I signaling. We have found that these regulatory circuits, as well as ISG expression patterns, vary significantly across different cell types at steady state and upon IFN-I stimulation. Recent technological advances now enable us to explore these cooperative ISG antiviral functions and negative feedback mechanisms at unprecedented depth and resolution. In the studies proposed here, we will identify subsets of ISGs sufficient to confer broad protection against multiple viruses using a novel single cell RNA-Seq strategy. This approach provides the throughput required to conduct complex combinatorial experiments while maintaining the high resolution to test specific hypotheses. Results may offer new broad spectrum antiviral therapeutic strategies, which would be of particular value against emerging viral pathogens. We will also investigate in detail the mechanisms by which IFN-I signaling establishes a lasting imprint on cellular responsiveness to subsequent IFN-I stimulation. This recently described but incompletely characterized phenomenon likely has important implications for successive infectious challenges and viral susceptibilities. Combining a unique collection of clinical samples, cutting edge technologies, and diverse and complementary expertise in immunovirology from our two laboratories, these studies are expected to address long standing, fundamental questions in innate antiviral immunity, as well as to pioneer new directions for developing antiviral therapies.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,662018,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +P22301,5R01AI153064-03,Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses,"ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no effective vaccines are available. Protective immunity against many pathogens can be achieved through long- lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly, our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.) Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced immune mechanisms that regulate the biology of Tfh cells. This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and durable neutralizing antibody responses. This finding could have a significant impact on vaccine development as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable protective antibody responses against many pathogens. We believe that the data generated in this proposal will be capable of moving this vaccine adjuvant towards clinical trials.",,2024,UNIVERSITY OF PENNSYLVANIA,626397,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22303,5R01AI148144-03,Clearance of Blood-Borne Arboviruses,"PROJECT SUMMARY Arboviruses cause serious human disease. Viremia level following arbovirus infection of vertebrates is a critical determinant of viral transmission cycles, global viral spread, and disease severity in individuals. Surprisingly, the factors that dictate viremia following arbovirus infection are poorly defined. We found that multiple arboviruses, including chikungunya (CHIKV), Ross River (RRV), o’nyong nyong (ONNV) and Zika viruses, are cleared from the circulation by phagocytic cells. Experiments in splenectomized mice showed that the spleen is dispensable for arboviral clearance. Instead, virus accumulates in the liver and clearance is independent of natural antibodies and complement factors, suggesting a non-opsonic mechanism. Consistent with this idea, clearance of circulating alphaviruses was blocked by competitive inhibitors of scavenger receptors (SRs) that mediate non- opsonic uptake of non-self and modified-self ligands. Remarkably, we found that single lysine (K) to arginine (R) mutations in the E2 glycoproteins of CHIKV and ONNV (E2 K200R), as well as RRV (E2 K251R), abrogated clearance of circulating alphavirus particles by phagocytic cells, and promoted rapid viral dissemination to distal tissues. Moreover, substitution of CHIKV E2 K200 with a variety of other amino acids also allows for clearance evasion, suggesting a specific interaction between key K residues and a host factor. Ks are targets for post- translational modification (PTM), and mass spectrometry analysis of E2 in virions revealed that CHIKV E2 K200 is ubiquitinated. These experiments have revealed a previously unrecognized pathway that controls arbovirus viremia and dissemination in vertebrates. We hypothesize that PTM of key Ks in viral glycoproteins licenses the capture of circulating arboviruses via SRs expressed on liver Kupffer cells (KCs). In Specific Aim 1, the cell types that capture circulating arboviruses will be defined. We also will determine the role of KCs in viral clearance and dissemination, and the development of anti-viral immunity. Finally, we will evaluate the role of phagocytic cells, and KCs specifically, in the clearance of a genera-spanning panel of arboviruses. In Specific Aim 2, we will define the spectrum of blood-borne arboviruses susceptible to SR-mediated clearance. We will use ELISA and cellular binding assays to determine the murine and human SR(s) that bind virus particles. Using SR knockout mice, we will determine the role of specific SRs in clearance of circulating arboviruses. In Specific Aim 3, we will define the role of E2 ubiquitination in the clearance of circulating CHIKV and RRV. We will use mass spectrometry-based proteomics to determine K residues in arboviral particles that are modified with ubiquitin or other PTMs. Finally, we will use a collection of reverse genetics systems to define the role of specific modified Ks in arboviral clearance from the circulation. This work will provide new mechanistic understanding of arbovirus clearance from the circulation. Elucidating these mechanisms could provide new insight into viral transmission, dissemination, and pathogenesis, identify new risk factors of severe disease, and reveal new therapeutic targets for the treatment of arboviral disease.",,2024,UNIVERSITY OF COLORADO DENVER,465481,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22305,5R01AI137472-06,Rational design and evaluation of novel mRNA vaccines against MERS-CoV,"Abstract Traditional strategies of vaccine development suffer from long-term and costly manufacture, and as a result, often fail to respond rapidly to newly emerging and reemerging infectious diseases. By contrast, messenger RNA (mRNA) is rising as a new technology platform to develop vaccines “on demand” against viral pathogens, offering attractive advantages such as cell-free production, non-viral delivery, as well as simple, fast and cost- effective manufacture. Further improvement upon mRNA's stability and translation efficiency, understanding of their immune mechanisms, and evaluation of their protective efficacy will facilitate the development of next- generation mRNA vaccine technologies against diverse viral pathogens. Middle-East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a highly pathogenic, emerging infectious virus posing a continuous threat to public health worldwide. There are currently no MERS vaccines approved for use in humans. MERS-CoV spike (S) protein, particularly its receptor-binding domain (RBD), is an important vaccine target. We have previously shown that MERS-CoV RBD contains a critical neutralizing domain capable of inducing strong cross-neutralizing antibodies and protecting human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice against MERS-CoV infection with outstanding efficacy. However, production of subunit vaccines and other traditional vaccines has limitations, such as low expression and complex purification. To address these unmet challenges, we propose to rationally design and evaluate novel mRNA vaccines, using MERS-CoV as a model pathogen and MERS-CoV S protein as a target antigen. We hypothesize that with appropriate modification and optimization, MERS-CoV S protein RBD-based mRNA vaccines will demonstrate improved stability, increased translation efficiency, and enhanced immunogenicity in both mouse and non-human primates (NHP) models, with protective efficacy on par with the RBD-based subunit vaccine. The specific aims are to (1) rationally design MERS-CoV mRNA vaccines with improved stability and translation efficiency, (2) carefully optimize mRNA formulations and immunization regimens towards in-vivo evaluation of their immunogenicity and mode of action in wild-type mice, and (3) comprehensively evaluate protective efficacy of MERS-CoV mRNA vaccines and elucidate their protective mechanisms in hDPP4-Tg mice and NHPs. Of note, we will also examine the utility of new technologies such as microfluidics and next-generation sequencing (NGS) analysis of B-cell response in mRNA vaccine development and evaluation. The long-term goal is to develop a safe and effective mRNA vaccine that is able to (1) maintain sufficient quantity and quality suitable for industrial- scale production, and (2) meet the WHO Target Product Profiles for rapid onset of immunity in outbreak settings and long-term protection of people at high ongoing risk of MERS-CoV. Together, the proposed project will shed light on protective mechanisms of mRNA vaccines, and provide much-needed information and guidelines for developing mRNA vaccines against diverse viral pathogens with pandemic potential.",,2025,GEORGIA STATE UNIVERSITY,742199,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2021 +P22306,1G20AI174721-01,ATCC's High Containment Facility Renovations in Support of NIAID and Pandemic Preparedness,"Project Summary: The proposed project aims to renovate ATCC's High Containment Facility (HCF) at the American Type Culture Collection (ATCC) in Manassas, Virginia. ATCC's 7,500 ft2 biocontainment facility was built in 2007 with funding from NIAID and has been dedicated to developing infectious disease strains and reagents needed to rapidly advance diagnostics, vaccines, and therapeutics against priority pathogens. Since 2003, ATCC has partnered with NIAID to centralize and provide critical scientific resources through the Biodefense and Emerging Infections Resources (BEI Resources) program. The NIAID established BEI Resources to provide the global research community with reagents, tools, and information for studying Category A, B, and C priority pathogens, emerging infectious disease agents, and other microbiological materials relevant to human health. Over the past 18 years, ATCC has provided over 1,360,000 reagents to over 14,000 investigators at 3,740 institutions in 119 countries spanning over 500 human pathogens in NIAID's priority portfolio. During this period, BEI Resources has provided critical materials for vital disease outbreaks, including H1N1, MERS, Ebola, and Zika. Over the past two years, ATCC has rapidly created more than 690 SARS-CoV-2 products; acquired, produced, and authenticated more than 165 stocks of SARS-CoV-2 for both general research and challenge studies; and shipped more than 86,000 research reagents to over 2,800 researchers in more than 70 countries for the development of countermeasures and basic research. The material provided by BEI Resources has been cited in more than 1,800 SARS-CoV-2 publications since February of 2020. In addition, ATCC has fostered collaboration and partnerships across NIAID programs and external working groups to share resources, information, and data to accelerate discoveries and harmonize scientific approaches for pandemic response and preparedness. ATCC's high containment facility houses laboratories essential for BSL-3 and Select Agent infectious disease research, product development, and large-scale reagent production for the research community. This proposal aims to renovate and upgrade the HVAC, decontamination, and security systems. The renovations also include upgrades to fixed equipment and interior finishing in the facility. The renovations will modernize the facility for use by 40 Ph.D. ATCC scientists, collaborators, and laboratory support staff. The products and services developed in the facility will support thousands of scientists globally each year to prepare and respond to pandemics. ATCC is seeking this opportunity for engagement with the NIAID to invest in this facility which has been foundational for the nation's pandemic response and preparedness.",,2024,AMERICAN TYPE CULTURE COLLECTION,3862721,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22307,5R01AI153044-02,Statistical innovation to integrate sequences and phenotypes for scalable phylodynamic inference,"PROJECT SUMMARY/ABSTRACT This proposal targets the design, development and distribution of Bayesian statistical methods and software to study the historical and real-time emergence of rapidly evolving pathogens, such as Ebola, human immun- odeficiency, inï¬Â'uenza, Lassa, SARS-CoV-2, West Nile, yellow fever and Zika viruses. The proposal exploits novel scalable data integration to equip us for large-scale epidemics and pandemics and help inform action- able public health policy. Our multidisciplinary team carries expertise across statistical thinking, data science, evolutionary biology and infectious diseases to leverage advancing sequencing technology and high-throughput biological experimentation that can characterize 1000s of pathogen genomes, phenotype measurements, eco- logical and clinical information from a single outbreak. Our chief innovations are three-fold. First, we will invent and implement scalable Bayesian phylodynamic techniques to integrate phenotypic measurements and study their correlated evolution with disease spread. Second, we will foster biologically-rich evolutionary models to map and understand heterogeneity in disease evolution through new efficient algorithms. Third, we will develop high-dimensional and mixed-type phenotype models to link concerted viral genotype / phenotype changes using massively parallel computing. Although no competing software exists to integrate phenotype and sequence data at this scale, we will compare restricted cases of our models with reduced datasets to current state-of-the-art approaches to evaluate computational performance improvement and bias that these limitations inject using real- world examples. This proposal will deliver low-level toolbox libraries and user-friendly software for deployment across a rapidly expanding range of large-scale problems in statistics and medicine.",,2025,UNIVERSITY OF CALIFORNIA LOS ANGELES,465948,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P22308,5R01AI146152-04,Validating the Flavivirus Envelope Protein as an Antiviral Target,"PROJECT SUMMARY Dengue virus (DENV) and other flaviviruses are major human pathogens that cause significant disease. Transmitted by widespread mosquito species, many of these viruses spread rapidly and can have a devastating impact on public health where prior immunity does not exist. There is thus a significant need for countermeasures to combat both current and future flavivirus threats. Major limitations in current antivirals development are the relatively small number of validated antiviral targets, most of which are viral enzymes (e.g., polymerases, proteases); the low barrier to resistance when direct-acting antivirals are used as monotherapies; and the narrow spectrum activity of most of these agents (“one bug, one drug”). New classes of targets that can mediate broad-spectrum activity against related viruses and that have high barriers to resistance are particularly needed to combat emerging viruses since we generally lack sufficient time and resources to develop new drugs on a useful time scale once these viruses pose significant threats. Small molecules targeting the flavivirus envelope protein, E, have the potential to mimic the humoral immune response by engaging their target extracellularly and blocking viral entry early in the replication cycle. We have identified multiple small molecule inhibitor series that bind to the DENV envelope protein, E, and inhibit E-mediated membrane fusion during viral entry even when only a minority of copies of E on the particle are inhibitor-bound. These compounds bind in a pocket between domains I and II and inhibit West Nile, Zika, and Japanese encephalitis viruses due to at least partial conservation of this site. We recently established a target-based assay and validated its use in the identification of new inhibitors of DENV and Zika E proteins that bind in the conserved pocket and that have more drug-like properties than our original inhibitors. Building on this work, we now propose a comprehensive plan to rationally optimize small molecule inhibitors of the DENV E protein as a potential anti-viral strategy. Towards this end, we will combine modeling and structure- guided drug design with an efficient screening cascade using complementary target-based biochemical, cellular and mechanistic assays to enable efficient optimization of two chemically distinct lead series. Our primary goal in this work is to demonstrate antiviral efficacy in a murine model of DENV infection, thus laying the foundation for first-in-class direct acting antivirals to treat the growing global threat that DENV poses.",,2025,STANFORD UNIVERSITY,961202,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22311,3G20AI167348-01S1,Regional Biocontainment Laboratory (RBL) Upgrade for Colorado State University (CSU),"Project Summary / Abstract The funding and implementation of this supplement is essential to maintain uninterrupted research and scholarly activity in CSU’s Rocky Mountain Regional Biocontainment Laboratory (RMRBL). Research activities that occur at the RMRBL directly address the RBLs’ missions to respond to and prevent global infectious disease threats. Our efforts are the evolution of over 4 decades of research conducted at CSU predominately sponsored by NIAID, and includes interdisciplinary research teams studying Flaviviridae, Togaviridae, Bunyavirales, Coronaviridae viral pathogens along with robust programs in mycobacteria, anti microbial resistance, and vector borne bacterial pathogens. The RBL is integral for this infectious disease research, training and other scholarly activities. The RMRBL recently benefitted from a G20 award specific to much needed modernization and infrastructure upgrades. However, these investments continue to be needed due to the complexity and high use of this facility. Here, we add to the Specific Aims of our parent G20 award to continue to make critical investments to improve our biosafety, animal modeling, and imaging research needs.",,2025,COLORADO STATE UNIVERSITY,3193195,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22312,5R01HL151498-03,Immunotherapy for acute lung injury secondary to influenza,"PROJECT SUMMARY/ABSTRACT The emergence of drug-resistant strains of human influenza A (IAV) and B viruses, as well as avian H5N1 virus with pandemic potential, to the only approved antiviral agents underscores the importance of developing novel antiviral strategies. We have engineered electrostatic complexes between cationic nanoparticles (i.e., chitosan) and anionic RNA that target airway epithelial cells in vivo during an IAV infection. These nanoplexes induce antiviral bioactivity directed against IAV in vivo with little or no untoward cellular or pulmonary responses. The nanoplex constructs stimulate early type I interferon (IFN) cellular responses through 5’- triphosphate (PPP)-RNA binding of the intracellular sensor, RIG-I. Additionally, the 5’PPP-NS1shRNA nanoplex formulation suppresses the translation of the IAV virulence factor, NS1, which inhibits RIG-I and host cell RNA maturation. The lung is well suited for an antiviral nanoplex strategy since it provides a portal for inhalation administration of bioactive nanoplexes. We have demonstrated that this strategy inhibits in vivo IAV replication therapeutically and avoids the “IFN paradox”, specifically, decreasing IAV lung injury, and IAV impairment of bacterial clearance from the lung. The focus of the current proposal is to optimize the therapeutic action of the 5’PPP-NS1shRNA nanoplex formulation in vitro and then in vivo. Additionally, we propose to carry out experiments recommended by the FDA article entitled “Antiviral Product Development: Conducting and Submitting Virological Studies to the Agency.” This includes in vitro and in vivo experiments to assess therapeutic efficacy (antiviral activity), pharmacokinetics, drug-drug interactions, and development of viral resistance. Additionally, because the 5’PPP-NS1shRNA nanoplex modulates the immune response, the FDA recommends examining possible unintended adverse effects resulting from actions on the immune system. Thus, we will also identify the specific immune system components that are altered, as well as assess the immune-mediated complications of an IAV infection including increased severity of the respiratory tract injury, and the risk of IAV-associated secondary bacterial pneumonia, a major cause of death in influenza cases. Specifically, we will examine the ability of 5’PPP-NS1shRNA nanoplexes to stimulate innate antiviral immunity, thereby changing infiltration of inflammatory cells, inflammatory cytokine milieu, adaptive immune responses, as well as decrease respiratory injury and IAV-associated impairment of bacterial clearance. In addition to assessing the clearance of IAV from the respiratory tract, we predict that the nanoplex construct will reduce the morbidity and severity of symptoms of influenza from drug resistant seasonal and pandemic strains, the highly pathogenic H1N1 swine-origin IAV virus (S-OIV) and H5N1 “bird flu”. These nano-technological approaches can also potentially treat other infectious (i.e., Ebola) or non-infectious lung injuries. Our proposal is designed to produce a novel antiviral nanoplex formulation for Phase 1 clinical trials as an Investigational New Drug.",,2024,STATE UNIVERSITY OF NEW YORK AT BUFFALO,436772,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H5,H1N1,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +P22315,1R43AI167394-01,Niclosamide Formulations for the Treatment of Influenza Infections,"Project Summary The principal goal of this project is to demonstrate that the FDA-approved anthelminthic drug, niclosamide, can be reformulated in a synthetic lung surfactant which can be aerosolized for the treatment of infections caused by respiratory viruses. The studies proposed in this SBIR Phase I application will be focused on testing this concept by suspending niclosamide loaded liposomes in our proprietary lung surfactant technology (Niclosurf) and testing candidate Niclosurf formulations in a mouse influenza challenge model. The effectiveness of Niclosurf as a treatment for respiratory viral infections caused by influenza will be evaluated.",,2023,"MOLECULAR EXPRESS, INC.",298479,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2022 +P22316,3UM1AI148685-03S1,Vaccine and Treatment Evaluation Unit at Saint Louis University,"Saint Louis University (SLU) seeks to expand its service to the Vaccine and Treatment Evaluation Unit (VTEU) network providing resources and expertise to help the network achieve its objectives of evaluating vaccines, preventive biologics, therapeutics and diagnostics for infectious diseases. Dr. Daniel Hoft, SLU VTEU PI, also serves as Co-PI for a VTEU Leadership Group (LG) application supported by all current VTEUs; however, regardless of who leads the LG, SLU will provide full support to promote outstanding VTEU research. Outstanding infrastructure for phase I-IV vaccine & therapeutic trials against priority pathogens: SLU has served as a VTEU for 29 years, conducted hundreds of phase I-IV trials in healthy and special populations of all ages, and can provide unique knowledge and extensive infrastructure to support VTEU network goals. Diverse knowledge scientific skills for trial design priority areas: SLU investigators include experts in vaccinology, immunology, seasonal and pandemic influenza, tuberculosis, biodefense, urgent/emergent pandemic trials, liver/enteric diseases, sexually transmitted infections, malaria/neglected tropical diseases, epidemiology and arboviral diseases. We also provide state-of-the art multi-platform omics core expertise. Urgent national preparedness trials: SLU has led urgent trials of vaccines against potential bioweapons (smallpox, anthrax, plague and tularemia), and emergent diseases (2009 H1N1 pandemic flu, avian H5 and H7 flu and Zika/Yellow Fever). In addition to streamlined institutional review and contracting, SLU can contribute containment facilities for select agent work and inpatient human challenge. Controlled Human Infection Models: SLU has developed the capacity for human challenge models to study influenza, parainfluenza, vaccinia, salmonella and tuberculosis immunity. We provide a 23-bed airborne containment facility for challenge studies with wild type GMP influenza strains, and have developed an active collaboration with SGS to standardize challenge protocols and obtain influenza challenge strains. Expertise in First-in-Human, investigator-initiated and pharmacokinetic/pharmacodynamic studies: SLU has completed dozens of first-in-human and investigator-initiated trials of vaccines against influenza, tuberculosis, HCV, enteric pathogens, potential bioweapons and emerging flaviviruses. Experimental biology studies of mucosal and systemic immunity with human samples of blood, tissue and mucosal samples have identified biomarkers and targets for iterative influenza and tuberculosis vaccine development. Sexually transmitted infection (STI) expertise: SLU's 10 years in the HIV Vaccine Trials Network provided SLU with expertise in STI. SLU also led a 44-site herpes vaccine efficacy trial (Herpevac), and two of the highest enrolling Herpevac sites have agreed to serve as Protocol-Specific Sites to expand our STI expertise. SLU ID follows ~450 HIV patients and closely collaborates with several molecular virologists. SLU looks forward to providing its expertise and capacities to meet the new ID challenges of the future.",,2023,SAINT LOUIS UNIVERSITY,151855,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Flaviviridae | Orthomyxoviridae | Yersiniaceae | Novel Pathogen,Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza | Plague | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics,2021 +P22317,3UM1AI148685-03S2,Vaccine and Treatment Evaluation Unit at Saint Louis University,"Saint Louis University (SLU) seeks to expand its service to the Vaccine and Treatment Evaluation Unit (VTEU) network providing resources and expertise to help the network achieve its objectives of evaluating vaccines, preventive biologics, therapeutics and diagnostics for infectious diseases. Dr. Daniel Hoft, SLU VTEU PI, also serves as Co-PI for a VTEU Leadership Group (LG) application supported by all current VTEUs; however, regardless of who leads the LG, SLU will provide full support to promote outstanding VTEU research. Outstanding infrastructure for phase I-IV vaccine & therapeutic trials against priority pathogens: SLU has served as a VTEU for 29 years, conducted hundreds of phase I-IV trials in healthy and special populations of all ages, and can provide unique knowledge and extensive infrastructure to support VTEU network goals. Diverse knowledge scientific skills for trial design priority areas: SLU investigators include experts in vaccinology, immunology, seasonal and pandemic influenza, tuberculosis, biodefense, urgent/emergent pandemic trials, liver/enteric diseases, sexually transmitted infections, malaria/neglected tropical diseases, epidemiology and arboviral diseases. We also provide state-of-the art multi-platform omics core expertise. Urgent national preparedness trials: SLU has led urgent trials of vaccines against potential bioweapons (smallpox, anthrax, plague and tularemia), and emergent diseases (2009 H1N1 pandemic flu, avian H5 and H7 flu and Zika/Yellow Fever). In addition to streamlined institutional review and contracting, SLU can contribute containment facilities for select agent work and inpatient human challenge. Controlled Human Infection Models: SLU has developed the capacity for human challenge models to study influenza, parainfluenza, vaccinia, salmonella and tuberculosis immunity. We provide a 23-bed airborne containment facility for challenge studies with wild type GMP influenza strains, and have developed an active collaboration with SGS to standardize challenge protocols and obtain influenza challenge strains. Expertise in First-in-Human, investigator-initiated and pharmacokinetic/pharmacodynamic studies: SLU has completed dozens of first-in-human and investigator-initiated trials of vaccines against influenza, tuberculosis, HCV, enteric pathogens, potential bioweapons and emerging flaviviruses. Experimental biology studies of mucosal and systemic immunity with human samples of blood, tissue and mucosal samples have identified biomarkers and targets for iterative influenza and tuberculosis vaccine development. Sexually transmitted infection (STI) expertise: SLU's 10 years in the HIV Vaccine Trials Network provided SLU with expertise in STI. SLU also led a 44-site herpes vaccine efficacy trial (Herpevac), and two of the highest enrolling Herpevac sites have agreed to serve as Protocol-Specific Sites to expand our STI expertise. SLU ID follows ~450 HIV patients and closely collaborates with several molecular virologists. SLU looks forward to providing its expertise and capacities to meet the new ID challenges of the future.",,2023,SAINT LOUIS UNIVERSITY,272027,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Flaviviridae | Orthomyxoviridae | Yersiniaceae | Novel Pathogen,Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza | Plague | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics,2021 +P22318,5R01AI154274-02,Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach,"The current COVID-19 crisis starkly illustrates the need to develop new modalities for the therapeutic treatment of pathogenic single-stranded RNA (ssRNA) viruses, including against novel viruses that have yet to emerge. Human oxysterol-binding protein (OSBP) has recently been determined to be a critical mediator in the replication of a broad spectrum of ssRNA viral human pathogens, including the enteroviruses, rhinovirus, hepatitis C, Zika virus, Dengue fever viruses, and coronaviruses. OSBP is an ER-located, non-enzymatic protein reported to function as an important lipid sensor and lipid transporter in eukaryotic cells. Published research, including our own recent publications, has established the antiviral activity of structurally-diverse OSBP- targeting small molecules against multiple RNA pathogenic viruses. These discoveries present the opportunity for a paradigm shift in antiviral drug development: potentially drug targeting a human host protein, OSBP, that is required for viral proliferation of a broad-spectrum of RNA viruses, as opposed to targeting viral proteins present in individual viruses. We have discovered that transient, low dose treatment with the OSBP-targeting compound OSW-1-compound induces a longterm, multigenerational repression of OSBP, and the cells with repressed OSBP show a pronounced inhibition of ssRNA viral replication. Our preliminary results show that the OSW-1- compound has prophylactic antiviral activity at low nanomolar concentrations against several ssRNA viruses, including against one coronavirus tested. The longterm repression of OSBP, triggered by OSW-1, has no effect on cellular division, viability, or morphology. The purpose of this proposal is to understand the cellular role of OSBP in innate antiviral response. Our preliminary results show that OSBP: 1) regulates mTORC1 activity, 2) induces autophagy; 3) slows global protein translation; and 4) activates alternative splicing nonsense- mediated decay (AS-NMD) process, which is an RNA regulatory process. All of these OSBP- involved cellular processes would limit ssRNA viral replication individually, but there is little insight into the organization of these systems to establish a coordinated antiviral response.Our overall hypothesis is that OSBP serves in a major regulatory role to coordinate a multifaceted innate antiviral response to ssRNA infection. We propose a complete model of how OSBP senses early- stage viral infection and then triggers a multisystem response to block viral replication in cells, including through modulating mTOR1C activity and the AS-NMD system.",,2026,UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR,397762,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22319,1R01AI159290-01A1,The role of TRIM2 and SIRPA in New World Arenavirus entry,"New world hemorrhagic fever arenaviruses (NWAs), such as Junín virus, are rodent-transmitted viruses that cause ~30% mortality when they zoonose into humans. The mechanism by the NWAs induce disease is still not certain, although it likely includes induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Survivors of Junín infection develop strong humoral immune responses, suggesting that controlling infection at early times post-infection is critical for virus clearance. Although an effective Junín virus vaccine has decreased disease incidence, sporadic cases of this as well as the other known and novel NWAs for which there are no vaccines or effective therapeutics still occur. It is well-established that the clade B pathogenic NWAs bind to transferrin receptor 1 and other receptors on the cell surface, but the steps leading to their entry from an acidic cellular compartment are not well-determined. We recently performed a siRNA screen with pseudotyped viruses bearing a pathogenic Junín glycoprotein with the goal of finding host genes involved in entry that could serve as therapeutic targets. We found that TRIM2, a member of the tripartite motif family that includes well-known members of the host's intrinsic defense against viral infections, limits NWA endocytosis into cells. By probing the TRIM2 interactome for other host proteins that block NWA infection, we discovered that SIRPA, a cell surface protein that inhibits macrophage phagocytosis of tumor and dead cells and erythrocytes, also decreases infection. Importantly, SIRPA, unlike TRIM2, inhibits infection by various human pathogenic viruses that require trafficking to an acidic compartment, including VSV, Zika virus, LCMV and Ebola and SARS-Cov-2 pseudoviruses. Our data suggest that TRIM2 and SIRPA act at the viral entry/internalization step. These finding suggests that there are common mechanisms that regulate virus endocytosis and phagocytosis. We propose here to further investigate the overlap between virus-mediated endocytosis and phagocytosis in vitro, ex vivo and in vivo in three aims that will 1) investigate the overlap in the NWA entry and phagocytosis pathways; 2) determine where TRIM2/SIRPA inhibition of infection occurs; and 3) use TRIM2, SIRPA and other relevant knockout mice to probe the roles of these proteins in cell-type specific and in vivo infection by replication-competent NWAs. In addition to providing mechanistic insight into the entry of NWAs into cells, these studies have the potential of increasing our understanding as to how host factors limit infection and could lead to new approaches to therapeutic intervention.",,2027,UNIVERSITY OF ILLINOIS AT CHICAGO,441075,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P22320,1G20AI174723-01,BSL3 Enhancements for RNA Virus Pandemic Preparedness,"Program Summary/Abstract The University of Massachusetts Chan Medical School (UMass Chan) seeks NIH G20 funding to repair, renovate, and modernize the existing Biosafety Level 3 (BSL3) and Animal BSL3 (ABSL3) facilities to enhance current research on RNA viruses of pandemic potential. As an internationally recognized leader in infectious disease research, UMass Chan has made pivotal contributions to this field, including work on the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), highly pathogenic avian influenza virus, Newcastle disease virus, and Zika virus. At the start of the coronavirus 2019 (COVID-19) pandemic, we quickly became one of the leading institutes for research and clinical trials on SARS-CoV-2. Our researchers obtained several awards from the NIH, NSF, and Department of Defense, as well as private foundations for these studies. As a leading site for COVID-19 clinical trials, UMass Chan is uniquely poised to bridge clinical and basic research studies on these RNA viruses by enabling essential research on patient samples to complement in vitro and in vivo studies. Our findings can be translated to develop novel prevention and therapeutic strategies leveraging our world-renowned RNA Therapeutics Institute, our Institute for Drug Resistance, and our partnership with MassBiologics for vaccine development, making UMass Chan a powerhouse for bench-to-bedside translational research. The UMass Chan BSL3 Core Laboratories have seen a staggering increase in usage due to the pandemic. Our BSL3 and ABSL3 facilities need major updates and renovations to keep pace with our research programs and continue to provide a safe, modern, and efficient lab for BSL3 work. The last time these facilities were completely renovated was over a decade ago (2003â€Â""2005 for our ABLS3 and 2010â€Â""2014 for our BSL3). We will modernize the existing BSL3 and ABSL3 facilities by updating the ceiling and ventilation systems, installing new autoclaves, maximizing the existing footprint by removing outdated equipment, and updating cameras for safety. These updates will significantly enhance research on RNA viruses of pandemic potential by addressing deficiencies that have caused prolonged downtime for repairs, and by enhancing the resilience of critical building systems. Our UMass Chan Facilities and Campus Services team has extensive experience executing design, renovations, and oversight of the operations and have worked with the NIH on previous G20 and C06- funded improvements to our facilities. The G20 funding will also be backed by strong institutional support for this project and a commitment to fully equip the updated space with state-of-the-art scientific instruments and other equipment needed to maintain the productivity of currently funded and future research on SARS-CoV-2 and other BSL3-level RNA viral pathogens. With G20 funding, our BSL3 and ABSL3 labs can get much- needed updates to support our faculty as they continue to make ground-breaking fundamental discoveries with translational potential to address SARS-CoV-2 and other RNA viruses of pandemic potential.",,2025,UNIV OF MASSACHUSETTS MED SCH WORCESTER,3994219,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22321,1G20AI174708-01,Stony Brook University Laboratory for Comparative Medicine to Support Pandemic Preparedness,"PROJECT SUMMARY/ABSTRACT The Laboratory for Comparative Medicine (LCM) at Stony Brook University is a recently constructed, state-of- the-art animal biosafety level 3 (ABSL3) facility. The LCM is actively engaged in basic, translational, and preclinical research on SARS-CoV-2, the viral agent of the current COVID-19 worldwide pandemic. Research in the LCM serves multiple individual investigators and groups, both within and outside of Stony Brook University, and includes commercial as well as academic interests. Stony Brook has a long history of excellence in microbial pathogenesis research, including studies on pandemic potential viruses of concern in the families Coronaviridae (SARS-CoV-2), Bunyavirales (Hantaviruses), Flaviviridae (Dengue, Zika, and Powassan viruses), and Picornaviridae (Poliovirus). Stony Brook virologists are also conducting ongoing studies in Human Immunodeficiency Virus and Influenza A Virus. Our research over the past five years has covered three different RNA virus families relevant under the American Pandemic Preparedness/pandemic preparedness effort, and our cumulative experience covers four of the viral families of concern. In addition to viruses of concern, active research at Stony Brook and in the LCM includes work on the highly virulent bacterial agents Rickettsia spp. of the spotted fever group, Francisella tularensis, a Select Agent and cause of the zoonotic disease tularemia, and Mycobacterium tuberculosis, causative agent of tuberculosis. To improve facility operations and enhance ongoing and future research in the LCM, we are requesting four upgrades to the LCM: 1) Replacement of the high temperature hot water unfired steam boilers and conversion of the high temperature and hot water systems; 2) Purchase and installation of a washer for animal cages and racks; 3) Purchase and installation of a fluorescence-activated cell sorter and custom biosafety enclosure; and 4) Acquisition of a real-time, quantitative reverse-transcription PCR machine. The requested upgrades will support and improve pandemic preparedness-relevant research in the LCM, advance studies on highly virulent and emerging pathogens, and provide enhanced resources not only to Stony Brook researchers, but also to State and regional efforts to combat current and future pandemic threats. The requested improvements will support the development of antiviral programs and antimicrobial preventive and therapeutic measures.",,2025,STATE UNIVERSITY NEW YORK STONY BROOK,2933079,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Bunyaviridae | Coronavirus | Flaviviridae | Unspecified,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P22322,1R21AI169309-01,Defining the optimal type and timing of COVID-19 vaccine in pregnancy,"PROJECT SUMMARY/ABSTRACT Pregnant individuals are more likely to require invasive mechanical ventilation or die from complications related to coronavirus disease 2019 (COVID-19) than non-pregnant women. COVID-19 vaccination in pregnancy can prevent the consequences of infection for the mother and provide passive immunity to newborns through placental transfer of vaccine-induced antibodies. The maternal immune system undergoes adaptive changes during pregnancy characterized by both active suppression of immune responses against the developing pregnancy and pro-inflammatory signals to promote healthy implantation and initiate labor. The central hypothesis is that the adaptive immunologic changes in pregnancy lead to differences in the development of vaccine-induced immunity depending on the gestational age at vaccination and/or the vaccine platform used. The overall objective of this proposal is to address important knowledge gaps including limited information regarding cellular immune responses following maternal vaccination, immune responses after vaccination in early pregnancy, and comparison of immunogenicity across different vaccine platforms. The research proposed is innovative because we will use a comprehensive immune profiling approach to quantify functional cellular and antibody responses in order to define the COVID-19 vaccine type and timing that optimizes robust and durable maternal vaccine-induced immunity (Aim 1) and neonatal passive immunity from placental transfer of viral neutralizing antibody (Aim 2). The proposed research is significant because it is expected to provide data to inform clinical recommendations for COVID-19 vaccines in pregnancy to improve maternal and neonatal outcomes. The long-term goal will be to provide preliminary data for a larger study evaluating vaccine efficacy for pregnant individuals and their neonates. The knowledge provided by this proposal will also inform future vaccine development for other important and emerging pathogens in pregnancy.",,2023,BETH ISRAEL DEACONESS MEDICAL CENTER,216125,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22324,5R01HD102445-02,Childhood Outcome After In Utero ZIKV Exposure,"PROJECT SUMMARY Clinically normal children exposed to Zika-virus (ZIKV) in utero may evidence abnormal neurodevelopment during the first few years of life even in the absence of the severe phenotype of congenital Zika syndrome (CZS). This is an important problem because the majority of children with in utero ZIKV exposure do not develop CZS but are at risk for neurodevelopmental abnormalities as they mature. The risk for neurodevelopmental impairments at school age in children with in utero ZIKV exposure, who do not have CZS, is not known because children have neither reached nor been studied at this critical age. The long-term goal is to recognize the spectrum of neurologic outcomes for children exposed to ZIKV in utero, which will enable appropriate follow-up guidelines, educational interventions, and therapies to support all children exposed to ZIKV. The objective of this application is to identify school age abnormalities in neurodevelopment and the domains affected and to evaluate for brain structural and functional differences among children in Colombia and in the US with ZIKV exposure in utero who do not have CZS. Guided by strong preliminary data, we will test two specific hypotheses: 1) that executive and motor function will be negatively impacted in ZIKV-exposed children compared to controls; and 2) that quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls. The children will be followed at age 5 and 7 years using a specifically designed set of neurodevelopmental assessment tools and quantitative structural and functional neuroimaging. Neurodevelopment will be assessed by an approach utilizing validated questionnaires and child assessments that measure executive function, behavior, motor function, and intellectual ability. The advanced brain MRI will provide a multimodal assessment of brain structure and function. The approach is innovative because of access to two uniquely well characterized cohorts, one from the Caribbean coast of Colombia who had sequential fetal and neonatal neuroimaging and had early neurodevelopmental evaluations and a cohort from a congenital Zika program in the United States with exposure by travel or emigration. The proposed research is significant, because it will address a key question in child health by focusing on neurodevelopmental abnormalities in children following in utero ZIKV exposure that can manifest at school age. Ultimately, such knowledge has the potential to immediately inform the development of guidelines for neuropsychological and imaging assessment at school age for children with in utero exposure to ZIKV. Completion of the aims will improve identification of abnormal neurologic outcomes in children who had exposure to ZIKV in utero. The knowledge to be gained from this work is essential to be done now and is important to families, care providers, public health policy authorities, and federal agencies. It may be also applicable to future congenital infectious epidemics and potentially other perinatal exposures.",,2025,CHILDREN'S RESEARCH INSTITUTE,699961,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +P22325,1R01EY032495-01,Role of Zika virus (ZIKV) infection in glaucoma pathobiology,"PROJECT SUMMARY The overall goal of this project is to investigate the role of Zika virus (ZIKV) in glaucoma pathobiology. ZIKV is an emerging viral pathogen that causes microcephaly and leads to severe ocular complications in newborns born to ZIKV infected mothers. Although the ocular manifestations of ZIKV are primarily reported to affect the posterior segment of the eye resulting in chorioretinal atrophy, withering of the retina and choroid, and optic nerve abnormalities, several clinical case reports showed the involvement of the anterior segment resulting in glaucoma. Studies from our laboratory, as well as those of others, have shown that ZIKV can cause glaucomatous pathology including an increase in intraocular pressure (IOP), retinal ganglion cell (RGC) loss, and optic nerve damage. The offspring of ZIKV infected dams have shown increased IOP and RGC loss and the presence of anti-flavivirus-antibody in these mice correlates with significantly enhanced glaucoma pathology due to antibody-dependent enhancement. Until the recent ZIKV epidemics, glaucoma has been primarily considered as a genetic and age-related disease and has not been reported among infants exposed to infection during gestation. Several studies have now reported that ZIKV can cause congenital glaucoma in infants born from mothers who were infected during pregnancy. Considering the fact that there is an endemic transmission of ZIKV in >84 countries, it is imperative to investigate the link between ZIKV and glaucoma to develop new prognostic and therapeutic tools to combat this global health threat. Our laboratory has developed several in vitro and in vivo models to study the pathobiology of ocular ZIKV infections. In our recent study, we reported that ZIKV can infect and replicate in human primary Trabecular Meshwork cells (HTMC). More recently, we performed RNAseq analysis and discovered that ZIKV infection of HTMC leads to transcriptomic alteration and dysregulation of several pathways including those that modulate ER stress response, autophagy, hypoxia, and ECM organization. Furthermore, ZIKV-infected mice exhibited increased IOP, ER stress, and autophagy in the anterior segment of the eye. ZIKV infection also caused RGC death and loss of RGC and optic nerve damage leading to disruption of anterograde axonal transport. Based on these novel findings, we hypothesize that ZIKV induces ER stress and autophagy resulting in TM death and dysfunction, increased IOP, and the development of glaucoma. Two specific aims are proposed to test this hypothesis. Aim 1 will determine the role of ZIKV induced ER stress in TM dysfunction and the pathobiology of glaucoma using C57BL/6 (WT) and IFNAR1-/- mice/pups and whether the reduction of ER stress alleviates ZIKV induced glaucomatous pathology. Aim 2 will investigate the role of autophagy using HTMC, and mouse models and evaluate the therapeutic efficacy of an FDA approved drug, hydroxychloroquine (HCQ) in ZIKV induced glaucoma. The anticipated results will establish the role of ZIKV infection in the pathogenesis of glaucoma and elucidate the molecular mechanisms and pathway-mediated therapeutic targets for future treatments.",,2026,UNIVERSITY OF MISSOURI-COLUMBIA,395936,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2021 +P22326,5R01AI149486-02,Understanding the mechanisms of antibody-mediated transcytosis of ZIKV within the placenta,"Humoral immunity is an essential component of the immune response to flavivirus infection. Primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly apparent that secondary infection with a closely related flavivirus strain can result in immunological cross-reactivity; however, the consequences to infection outcome are hotly debated and controversial. Zika virus (ZIKV) is a mosquito-borne flavivirus, which has a high degree of sequence and structural homology to Dengue virus (DENV), and is responsible for continuing epidemics of fetal congenital malformations within the Americas since its introduction to Brazil in 2015. Prior flavivirus exposure has been strongly associated with generation of cross-reactive antibodies that bind to and/or neutralize ZIKV. A unique aspect of ZIKV pathogenesis is the ability of the virus to seed infection within the placenta, however, the mechanisms of transplacental ZIKV infection are not well understood. The overall goal of this proposal is to understand how cross-reactive antibodies facilitate ZIKV transcytosis and seed infection of the placenta. The placenta is composed of anchoring chorionic villi, which penetrate the uterine wall, as well as floating chorionic villi that are bathed in maternal blood pooling in the intervillous space. Recent epidemiological observations found that between 20-50% of pregnant women with possible ZIKV exposure had detectable ZIKV RNA in the placenta. Another report found that ZIKV can persist in the placenta for over 200 days post mother onset of Zika symptoms. We discovered that Hofbauer cells, fetally- derived placental macrophages located within the villus stroma, are permissive for ZIKV infection. To identify a potential mechanism by which ZIKV gains access to the villous stroma, we recently evaluated the impact of cross-reactive dengue antibodies in mediating transplacental infection. Using an ex vivo placental explant model, we observed profound enhancement of ZIKV infection of human mid-gestation floating chorionic villi with ZIKV immune complexes generated using either DENV or ZIKV cross-reactive convalescent serum or monoclonal antibodies. Similar to histological analysis of placenta from infected pregnant mothers, ZIKV replicated exclusively within Hofbauer cells. Based on these observations, we hypothesize that the Fab fragment (specificity for ZIKV) and the Fc domain (affinity for FcRn and FcγR) of IgG impacts antibody-mediated ZIKV transplacental infection. Moreover, we believe that gestational age of the placenta dynamically influences the efficiency of ZIKV transcytosis and placental infection. Moreover, we believe that gestational age of the placenta dynamically impacts ZIKV transcytosis and placental infection. In this proposal, we seek to address the following outstanding questions: 1) How does IgG antibody specificity, affinity and Fc/FcRn interactions impact ZIKV transplacental infection? and 2) How does placental gestational age impacts antibody-mediated infection of Hofbauer cells? Our studies will likely reveal therapeutic targets and provide insights for development a vaccine to protect against ZIKV infection.",,2025,EMORY UNIVERSITY,757655,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P22327,5K01MH123258-02,Evaluating risks of ZIKV co-infection in SIV-infected macaques,"PROJECT SUMMARY Over 36 million people are living with HIV and there is large geographic overlap for areas endemic with flavivirus infection. Despite the occurrence of large flavivirus outbreaks, there is a severe lack of knowledge regarding the impact flavivirus infections may have on people living with HIV (PLWH). It is unclear what effect HIV co-infection has on the clinical consequences of flavivirus infection and current studies in humans are limited by low patient numbers and inconsistent incorporation of HIV disease status into interpretations of flavivirus disease. Non- human (NHP) models of Zika virus (ZIKV) infection recapitulate several aspects of human disease and are ideal for evaluating the impact of human flavivirus infection in people living with HIV. However, no established HIV- ZIKV co-infection animal model exists. In this proposal, we will study the natural history of HIV co-infection with flaviviruses to understand the risks, causes, and clinical outcomes in PLWH. Previously in NHPs, we showed that CD16+ monocytes are the major in vivo blood targets of ZIKV and similar results have been found in humans. Monocyte frequencies increase during HIV infection and although ART reduces total frequencies in HIV infected persons, CD16+ monocytes remain elevated. We will investigate the hypothesis that HIV infection promotes susceptibility to flavivirus infection by decreasing anti-viral innate and adaptive immune responses, increasing inflammation, and expanding cellular targets of infection, including monocytes. HIV invasion of the central nervous system (CNS) is mediated by CD16+ monocytes, therefore monocytes could also act to spread ZIKV to the CNS and promote neurological disease. Thus, HIV infection could promote ZIKV pathogenesis and neuroinvasion by expanding the cellular target pool and inducing inflammation. Additionally, we hypothesize that enhanced ZIKV pathogenesis occurs in PLWH, and we will experimentally test this using an NHP model of SIV infection. Specifically, in Aim 1 we will evaluate whether cells from SIV infected animals support greater ZIKV replication. In Aim 2 we will determine whether ZIKV pathogenesis is enhanced in SIV-infected macaques. We will determine whether SIV infection promotes invasion of ZIKV into the CNS and determine the innate and adaptive immune responses corresponding to enhanced infection. These studies will provide significant insights into the potential risk of enhanced ZIKV pathogenesis in the HIV population and determine if PLWH have a greater risk of ZIKV-associated pathologies. The goal of this K01 is to support the transition of developing my own independent research program focused on understanding the impact of viral co-infections in PLWH. In order to achieve this goal I will expand upon my previous training using NHP models of HIV and ZIKV human infection, will leverage the resources at the University of Washington and the Washington National Primate Research Center, and will work closely with my mentors, Dr. Deborah Fuller and Dr. Michael Gale.",,2023,UNIVERSITY OF WASHINGTON,139227,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Immunity",2020 +P22328,1R21MH125034-01A1,Maternal ZIKV infection as an environmental risk factor for mental illness,"Abstract A large body of evidence has identified maternal immune activation following viral infection as an environmental risk factor for mental illness. Maternal immune signals, including inflammatory cytokines, can access fetal tissues and permanently alter brain function and behavior in otherwise developmentally normal offspring. Indeed, maternal infection with a number of viruses has been associated with the development of mood disorders and/or psychosis in offspring, and these associations are intensified in offspring with preexisting genetic risk factors for mental illness. Zika virus (ZIKV) is an emerging pathogen recently identified as an etiologic agent of severe neurodevelopmental syndromes following infection during the early stages of gestation. However, the impacts of maternal ZIKV infection during late gestation have not been adequately addressed, nor has the potential impact of maternal ZIKV infection on the mental health of developmentally normal offspring been investigated. Here, we propose to use a murine model of late-term maternal ZIKV infection to characterize neuroimmune signaling at the maternal-fetal interface. To study the consequences of this signaling, we will also assess the impact of late-term maternal ZIKV infection on the development of behavioral abnormalities in motor, cognitive and social domains that underlie psychiatric disorders (e.g., autism, schizophrenia). Finally, we will use an established mouse model of human 22q11.2 deletion syndrome, a common genetic susceptibility factor for mental illness, to examine interaction effects of maternal ZIKV infection with genetic risk for behavioral abnormalities. These studies will establish the potential pathologic behavioral consequences of late-term ZIKV infection, informing future study and monitoring efforts for individuals affected by this globally emerging pathogen.",,2023,"RUTGERS, THE STATE UNIV OF N.J.",225697,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Post acute and long term health consequences",2021 +P22329,3R41AI129119-02S1,Development of Zika viral pseudoinfectious virus as Zika vaccine candidate,"Executive Summary of Predicate SBIR/STTR Phase I Grant and Team TenGen Biomedical Co. and Howard University received an STTR Phase I grant (5R41AI129119-02) from the National Institute of Allergy and Infectious Diseases (NIAID) in 2017. The overall objective of our predicate STTR Phase I grant is to develop a safe, effective, and affordable Zika vaccine based on the novel concept of the third generation of flavivirus vaccine. Zika virus (ZIKV) epidemics and the association of ZIKV infection with Guillainâ€Â""Barré syndrome, and congenital disabilities, including microcephaly, led the World Health Organization to declare ZIKV a “Public Health Emergency of International Concern” in 2016. Therefore, an effective Zika vaccine is urgently needed. The project proposed four specific aims: 1. Construction of subgenomic replicon for ZIKV, 2. Development of stable packaging cell lines providing ZIKV structural protein C in trans. 3. Harvest of ZIKV PIVs from infected packaging cell line and analyzing the stability of the packaging cell lines and PIV during passages, 4. Preliminary analysis of the safety and immunogenicity of the proposed vaccine in mice. In the past two years, we have made 8 significant achievements forward the specific aims: 1. Generation of Infectious cDNA Clones of Wildtype and Mutant Zika Virus 2. Development of stable Vertebrate Specific Replication Defected ZIKV by selective adaptation 3. DNA sequencing of the stably replication-defective in vertebrate cells-ZIKV (VSRD-ZIKV) and analysis of new engineered mutations 4. Preliminary evaluation of VSRD-ZIKV in both newborn and 3-week-old immunocompromised mice 5. Prime-boost VSRD-ZIKV vaccination provides robust protection against lethal ZIKV challenge in immunocompromised mice 6. Vaccination with VSRD-ZIKV is associated with ZIKV-specific humoral immunity and CD8+IFN- + responses 7. VSRD-ZIKV provides protection and prevents viral accumulation in the testes of male mice challenged with lethal ZIKV 8. Immunization with VSRD-ZIKV protects against vertical transmission in pregnant mice challenged with lethal ZIKV In addition, we recently published a paper based on this study: Wan S, Cao S, Wang X, Zhou Y, Yan W, Gu X, Wu TC, Pang X. Generation and preliminary characterization of vertebrate-specific replication-defective Zika virus. Virology. 2020 Oct 6;552:73-82. doi: 10.1016/j.virol. 2020.09.001. Online ahead of print. PMID: 33075709 We proposed the I-Corps team included three highly qualified key investigators. Chris D. Ta, MBA. CEO of TenGen Biomedical Co. and he has over seventeen years of experience in industry development; Xiaowu Pang, Ph.D. Principal Investigator of the STTR Phase I project and he has been driving the project; and Xinbin Gu, MD. Ph.D. Co-founder of TenGen Biomedical Co. and Co-Investigator of the STTR Phase I project. Dr. Gu has been leading the visionary on the team. All three members are committed to the time requirements of the program.",,2021,TENGEN BIOMEDICAL CO.,52000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Vaccine design and administration | Vaccine trial design and infrastructure",2021 +P22330,1U01AI153416-01A1,"Living in the post-Zika world: Impact of interactions between dengue and Zika viruses on diagnostics, antibody dynamics, and correlates of disease risk","SUMMARY Worldwide, over 3 billion people are at risk of infection and disease caused by dengue virus 1-4 (DENV1-4) and Zika virus (ZIKV), both potentially severe flaviviral diseases transmitted by Aedes mosquitoes. The devastating effects of endemic dengue across the tropics and subtropics are well documented. The recent Zika pandemic galvanized research as Zika swept across Latin America. Three years after the peak of the Zika pandemic, major dengue epidemics have started to re-occur; however, the future of flaviviral disease across areas with widespread ZIKV immunity is unknown. In this R01, we propose to develop new tools and address key knowledge gaps in flaviviral transmission and immunological interactions between DENV and ZIKV to understand how widespread ZIKV immunity impacts subsequent dengue disease and to inform evaluation of dengue and Zika clinical vaccine trials and post-licensure studies. Based on our serological, epidemiological, and clinical data to date, our overall hypothesis is that DENV1-4 and ZIKV are antigenically closely related and that immune interactions mutually affect transmission and disease severity. We will address this hypothesis with the ongoing Pediatric Dengue Cohort Study (PDCS, 2004-present), a community-based prospective cohort study in Managua, Nicaragua, following ~4,000 children, now in its 17th year. Samples from the PDCS, as well as companion studies in Managua, provide documented infection and disease data, as well as banked serum samples for over a decade before the arrival of ZIKV. The proposed study extends the cohort, ensuring that we are able to fully document the interactions of these viruses from the pre- to post-Zika eras. In Aim 1, we will develop innovative serologic tools based on glycan-fusion-loop-masked envelope proteins and new algorithms to distinguish DENV and ZIKV infection histories, critical for vaccination and epidemiological studies of dengue and Zika. We will then test our hypothesis that pre-existing ZIKV immunity can enhance disease severity caused by DENV3 but protect against DENV1. In Aim 2, we will measure changes in anti-DENV and anti-ZIKV antibody-mediated immunity over time, estimate annual changes in protective and enhancing population immunity to each virus, collect entomological data, and use modeling approaches to evaluate popula- tion susceptibility to DENV and ZIKV infection and the potential for future epidemics by incorporating immunolo- gical and entomological data. In Aim 3, we will identify determinants of protective and disease-enhancing anti- body-mediated immunity of prior DENV infection on Zika and prior ZIKV infection on dengue disease and severity. With support of expert collaborators, we will use state-of-the-art tools (e.g., new monoclonal antibodies, innovative flavivirus antigens, and antibody Fc profiling) to analyze specific infection histories and uncover potential immune correlates. Overall, this program will define new vaccine companion diagnostic assays, the dynamics of the antibody response to DENV and ZIKV, and correlates of protection and pathogenesis for dengue and Zika, which should be useful for the development and evaluation of dengue and Zika vaccines.",,2026,UNIVERSITY OF CALIFORNIA BERKELEY,984840,Human Populations,Unspecified,Children (1 year to 12 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Immunity | Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2021 +P22331,5R01AI150837-02,Enhanced susceptibility to Zika virus during pregnancy: a role for maternal dengue antibodies,"Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is closely related to dengue virus (DENV). Since its discovery in 1947, ZIKV remained relatively unnoticed, causing small, local outbreaks primarily in parts of Africa and Asia, and was associated with minor symptoms, such as mild fever. However, in the last decade, ZIKV started to spread geographically across the Pacific islands, eventually reaching South America, where it caused an explosive outbreak that started in Brazil in 2015 and rapidly spread to other South and Central American countries. This has been accompanied by a startling link between ZIKV infection during pregnancy and the development of birth defects among fetuses and babies, including microcephaly. It is unclear what factors may have led to the massive ZIKV outbreak or the severe disease manifestations in the Americas, but one potential variable is that much of the at-risk population in the Americas has preexisting immunity to DENV. It is well documented that preexisting immunity to one serotype of DENV can alter the disease pathogenesis of a subsequent infection with a different DENV serotype, a phenomenon called antibody-dependent enhancement (ADE). Because ZIKV outbreaks have occurred in regions around the world where DENV is endemic and due to the high degree of relatedness of ZIKV and DENV, it is critical to understand and characterize the extent to which prior infection with DENV exacerbates ZIKV disease. In this application, we will focus on how DENV antibodies impact ZIKV infection in the context of pregnancy by utilizing three model systems (immunocompromised Stat2-/- mice, immunocompetent humanized STAT2 knock-in mice, and human placental explants infected with ZIKV ex vivo).",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,421878,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +P22332,5R01AI148264-02,Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates,"Abstract Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that recently caused an outbreak in the Americas. The establishment of ZIKV transmission cycle in tropical/sub-tropical regions that are endemic to other close-related flaviviruses such as Dengue virus (DENV) has raised concerns, mainly by their cross-immunological interactions and the implications of this for development of severe clinical manifestations. Several groups have demonstrated that DENV-immune serum from humans can enhance ZIKV infection in vitro and in vivo in an immunodeficient mice model. This phenomenon known as Antibody Dependent-Enhancement (ADE) has been linked to severe dengue clinical manifestations. Little is known about the effect of a previous immunity to ZIKV on a subsequent DENV infection. It is highly necessary to characterize correlates of protection in the control of a heterologous secondary DENV or ZIKV infection in the presence of previous DENV or ZIKV immunity in an immunological competent animal model that resemble the human immune system like the Non- Human Primates. Our group have preliminary data showing a potential protective role of the cellular immune response in dengue- immune or ZIKV-immune subjects during a heterologous secondary infection with ZIKV or dengue. The overall hypothesis behind this work is that the cross-primed cellular immune response may be critical controlling the DENV and ZIKV infection and provides heterologous protection against each other. To test this hypothesis, we propose a series of straightforward experiments by depleting the CD4+ or CD8+ or CD20+ cells at different time points before a primary or a secondary infection with dengue or ZIKV. This type of experiment has not been performed before in NHP. For these experiments we will use rhesus macaques bred and housed at the Caribbean Primate Research Center that has proven to be the purer Indian-origin macaque population of all populations in the USA or imported animals, without having a significant level of inbreeding. For first time in any study in the flavivirus field, we will use a large data on the MHC typing of this population to characterize specific CD4 and/or CD8 T cells epitopes playing a role in the T cells immune response against dengue and ZIKV. Understanding correlates of protection between ZIKV and DENV is essential to anticipate the outcome of the secondary infection, the design of diagnostics methods and more relevant, to support the design of highly effective ZIKV and DENV vaccines in the scenario of previous DENV or ZIKV immunity, respectively. Undoubtedly, NHP provide us with a unique immunological tool very close to the human system to provide the answers to the questions we are outlying on this application.",,2024,UNIVERSITY OF PUERTO RICO MED SCIENCES,695400,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22333,5R01AI153130-02,Early neural predictors and neuropathogenesis of sensorimotor neurodevelopmental deficits in macaque infants exposed to Zika virus in utero,"PROJECT SUMMARY Prenatal exposure to the Zika virus (ZIKV) poses a threat to the fetus, putting the neonate at risk for significant birth defects (termed congenital Zika syndrome) and neurodevelopmental deficits developing during early child- hood. There are currently no predictors to indicate which children will develop deficits and the neuropathologies underlying these deficits is not defined. It is critical to predict which infants will later develop deficits to max- imize long-term sensorimotor development and functional outcomes. Furthermore, understanding underlying neuropathogenesis is necessary to develop targeted interventions. The purpose of this grant is to define the long-term neurodevelopmental outcomes of ZIKV by rapidly obtaining data from highly controlled studies of rhesus macaques. Specifically, we will: Aim 1: Characterize sensorimotor neurodevelopmental outcomes in macaques with prenatal ZIKV expo- sure. Behavioral assessments focused on sensorimotor development may highlight the distinct developmental trajectories and increased deficits with age in ZIKV-exposed rhesus macaques. Because macaques develop more quickly than humans, sensorimotor neurodevelopmental differences that occur by year 3 may predict future impacts in children born with prenatal ZIKV exposure. Aim 2: Identify early neural predictors of sensorimotor neurodevelopmental deficits in ZIKV-exposed infant macaques with quantitative MRI, hearing and visual studies. We will describe differences between ZIKV-exposed and mock-infection control infants and identify individual differences within ZIKV-exposed in- fants to determine the full spectrum of brain abnormalities. Aim 3: Define neuropathology underlying sensorimotor neurodevelopmental deficits with quantitative brain histopathology. Using cellular quantification and organization of brain nuclei, we aim to identify the neu- ropathogenesis of congenital Zika syndrome to better create appropriate, targeted interventions for children. This study utilizes a large cohort of ZIKV-exposed infant macaques that have been born in other NIH-funded studies and capitalizes on our collaborative team of experts in neuropathology, neurodevelopment and neu- roradiology.",,2025,UNIVERSITY OF WISCONSIN-MADISON,769480,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P22334,275201800001I-0-759402100002-1,ZIP 2.0 STUDY CHILD COHORT WITH INTERIM ANALYSIS OF AGE 30 MONTHS DATA,"Zika virus (ZIKV) is an arbovirus (vector-borne virus) of the genus Flaviviridae. Infections were thought to be mild and self-limiting until 2015, when an epidemic was observed initially in Brazil of microcephaly and other birth defects in newborns following infection of the mother during pregnancy with Zika virus (ZIKV). Increasing evidence now points to ZIKV as the agent responsible for a variety of birth defects in newborns of mothers who become infected during pregnancy. The relationship of ZIKV infections in pregnant women with adverse outcomes of pregnancy is the subject of ongoing evaluation. Studies to date of infants born to infected women focus on those born with serious birth defects that constitute the congenital Zika syndrome (CZS). Whether there are latent effects on growth and development in infants who are born without CZS to Zika-infected women, and what those effects may be, is unclear. Longitudinal studies of infants born to Zika-infected pregnant women are needed to assess the broader spectrum and natural history of possible manifestations of intrauterine or intrapartum Zika exposure. In 2016, NIH initiated a large, multicenter, international observational study of the epidemiology, natural history, and pathogenesis of Zika in infants and pregnancy (the ZIP Study). The ZIP Study followed infants born to women at risk for Zika infection during pregnancy only through the infants’ first 12 months of life and completed its last patient last visit December 2019. In 2018, NIH initiated the ZIP 2.0 cohort study of Zika exposed children and unexposed control children from the ZIP Study or similar studies, following children beyond infancy to 42 months of age to evaluate the effects of Zika on child growth and development. Recent studies have found that infants who had in utero ZIKV exposure without CZS appear to be at risk for abnormal neurodevelopmental outcomes in the first 18 months of life1 and similarly observed high frequencies of anatomical and neurodevelopmental abnormalities in children without microcephaly who were exposed to ZIKV in utero2. One study found a gradient of risk of development delay according to head circumference, with severely microcephalic children at highest risk for delays while normocephalic ZIKV-exposed children showed similar risk to unexposed control children3. However, several other studies have observed abnormal neurodevelopment in the absence of microcephaly among children with intrauterine ZIKV exposure4,5. Those reports indicate that nearly all such children presented at least one developmental delay and that a significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities.",,2022,"WESTAT, INC.",2330566,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Women | Pregnant women,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Disease pathogenesis,2021 +P22335,1R01AI163188-01,Development of a Replicon RNA-based Vaccine against Dengue and Zika,"ABSTRACT The long-term goal of this project is to develop a dengue-Zika vaccine that provides protection against the four serotypes of dengue (DENV1-4) and Zika (ZIKV) viruses with maximal safety and efficacy. To date, flavivirus vaccine development has focused on the induction of neutralizing antibodies (nAbs), as they have been assumed to be the key mechanism for protection against natural infection. However, DENV and perhaps ZIKV are unusual in that weak Ab responses to vaccination or prior infection can induce antibody-dependent enhancement (ADE) of infection and pathogenesis during subsequent reinfections. In fact, DENV disease with severe sequalae has been documented in children given the only currently licensed DENV vaccine. Thus, the primary objective of this application is to develop an effective vaccine against DENV and ZIKV that cannot mediate ADE. We hypothesize that this vaccine will need to elicit both strong nAb responses and strong T cell effector responses that will counterbalance the presence of any ADE-mediating Abs, based on our work investigating the interplay between Ab and T cell responses to DENV and ZIKV. In particular, we have shown that CD8 T cells mediate cross- protection against heterotypic DENV and ZIKV infections, and that DENV vaccine-elicited CD8 T cells can prevent ADE. In addition, our preliminary data show that an RNA replicon-based vaccine expressing ZIKV nonstructural protein 3 elicits only T cell but not nAb responses and confers protection against ZIKV challenge in mice. Thus, we hypothesize that our combinatorial DENV-ZIKV vaccine expressing both Ab- and T cell-targeting proteins of DENV1-4 and ZIKV will produce humoral and cellular immune responses that provide robust, long-term protection against all five viruses. We will test this hypothesis by achieving the following Specific Aims: 1) To evaluate immunogenicity and efficacy of a DENV-ZIKV vaccine. 2) To determine the durability and mechanistic underpinnings of DENV-ZIKV vaccine-induced protective immunity.",,2026,LA JOLLA INSTITUTE FOR IMMUNOLOGY,712699,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P22336,1R01NS120182-01,Neurodevelopment after postnatal Zika virus infection in infant macaques,"PROJECT SUMMARY / ABSTRACT Intense research has focused on the neurologic effects of prenatal Zika virus (ZIKV) infection; however, the consequences of postnatal infection early in life are understudied. Infants exposed to ZIKV in utero but born without microcephaly can develop postnatal microcephaly, neurologic dysfunction, and neurodevelopmental ab- normalities, highlighting the potential of ZIKV to cause ongoing damage after birth. This damage is likely related to the exponential maturation of the brain that occurs during the first 2 years of life, particularly in temporal, prefrontal and parietal regions important for emotional, social and executive functions, including learning, atten- tion and memory. Our group has previously reported that postnatal ZIKV infection causes abnormalities in brain structure, function, and behavior in a pilot study of infant rhesus macaques (RMs) infected postnatally. Here, we propose to extend the scope and duration our prior pilot study and generate novel data regarding the impact of postnatal ZIKV infection on the developing brain. The Objective of this application is to bring new mechanistic insights into postnatal ZIKV infection to address the existing knowledge gap regarding outcomes and host-virus interactions. We will use our postnatal ZIKV-RM model to interrogate the neurobehavioral impact of ZIKV infection at different stages of postnatal brain develop- ment, with approaches that span from single cells to whole animal. This model of postnatal ZIKV exposure allows us to generate key data on the mechanisms by which ZIKV and/or the immune response to infection leads to cellular changes that ultimately result in aberrant postnatal development of limbic structures and behavioral def- icits later in life. We hypothesize that 1) ZIKV and/or the immune response to infection disproportionately affects limbic structures in the postnatally developing brain; 2) cellular changes in these limbic structures lead to aberrant neurodevelopment and abnormal behaviors; and 3) there may be a period of vulnerability to ZIKV during post- natal brain development. We will test our hypotheses in these Specific Aims: 1) Determine the spectrum of abnormal behavior and cognition following ZIKV infection of infant RMs at different stages of brain development; 2) Identify developmental trajectories of brain structure and function following postnatal ZIKV infection of infant RMs at different stages of brain development; and 3) Define the neurodevelopmental pathways and cell types impacted by postnatal ZIKV infection. This work will include RM infants infected with ZIKV at 1 or 6 months of age (equivalent to 4 and 24 month old humans) as well as age- and rearing-matched and viral mimic controls, that over their first 2 years of life will undergo a series of detailed assessments including validated tests of soci- oemotional behavior and cognition, structural and functional brain imaging, brain histology, stereology and single cell and bulk cell transcriptomics. Our results may have important public health implications for children living in ZIKV-endemic/epidemic areas as well as for travelers to these regions.",,2025,EMORY UNIVERSITY,707402,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Post acute and long term health consequences",2021 +P22337,5R21AI151427-02,Optimizing Zika NS5 Methyltransferase Inhibitors,"ABSTRACT Zika Virus (ZIKV) has emerged as a global public health threat because of its recent outbreaks and its link to microcephaly in newborns and Guillain-Barré syndrome in adults. To date, there is no vaccine or treatment available, highlighting an urgent need to develop effective therapeutics. Inhibition of ZIKV NS5 methyltransferase (MTase) is a promising anti-ZIKV strategy. However, current ZIKV MTase inhibitors generally suffer from low activity, lack of selectivity, or unfavorable drug-like properties, hindering testing of MTase inhibitors in the animal models of ZIKV infection. We have designed and synthesized a structurally novel inhibitor of ZIKV NS5 MTase, which possessed anti-ZIKV activity without significant toxicity. In this application, we will perform lead optimization to improve the potency, selectivity and drug-like properties of our ZIKV MTase inhibitors, aiming to identify MTase inhibitors that can be used in the ZIKV animal disease models. To accomplish the goal, we propose the following specific aims: Specific Aim 1. Design and synthesize ZIKV NS5 MTase inhibitors and evaluate them in biochemical and antiviral assays; Specific Aim 2. Assess selected ZIKV NS5 MTase inhibitors for their physiochemical and in vitro absorption, distribution, metabolism, and excretion (ADME) properties; and Specific Aim 3. Determine in vivo PK parameters of advanced ZIKV NS5 MTase inhibitors. We expect that the proposed research will significantly contribute to efforts in developing ZIKV MTase inhibitors as anti-ZIKV therapeutics.",,2023,UNIVERSITY OF MINNESOTA,231875,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Not applicable,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22338,5R01AI153433-02,A Novel Strategy for Generating Safe and Effective Flavivirus Vaccines,"The recent emergence and devastating impact of Zika virus (ZIKV) clearly demonstrates that arboviral emergence continues to defy accurate prediction and exposes our inability to rapidly respond to and control outbreaks. The medical and veterinary importance of emerging flaviviruses is significantly exacerbated by the absence of available vaccines, therapeutics, and reliable control measures. Vaccination remains the most reliable strategy for outbreak prevention and control, but vaccine development intrinsically involves trade-offs between safety and immunogenicity. This study will develop a platform to overcome these trade-offs by combining the safety advantages of non-replicating platforms with the rapid and long-lived immunogenicity of a live-attenuated vaccine. We have developed a unique chimeric virus platform based on a novel insect-specific flavivirus (ISFV), Aripo virus (ARPV). Preliminary data shows ARPV's host restriction is noticeably later in the replication cycle than described for other ISFVs and is capable of entering vertebrate cells and developing a robust immune response in the absence of genomic replication. An ARPV/ZIKV chimera was developed to test our hypothesis that ARPV/ZIKV vaccination produces a rapid and robust innate, humoral, and cell-mediated immune response that elicits sterilizing immunity against subsequent ZIKV challenge. Preliminary studies show a single dose of ARPV/ZIKV produces a robust adaptive ZIKV-specific immune response that completely protects mice from viremia, weight loss, and mortality, while demonstrating exceptional safety in vivo. This platform is superior because of the increased safety of the chimera by virtue of its fundamental replication defect in vertebrate cells, increased immunogenicity due to a lack of inactivation requirements, and efficient genome delivery to target cells. This innovative and essential R01 aims to evaluate the safety profile, protective efficacy and mechanisms underlying the immunogenicity of ARPV/ZIKV vaccination via three aims: 1. Determine the efficacy of ARPV/ZIKV immunization for preventing ZIKV-induced disease in murine and rhesus macaque models. 2. Elucidate the correlates underlying vaccine-induced protection from ZIKV-induced disease in ARPV/ZIKV vaccinated murine models. 3. Evaluate the safety profile of this vaccine candidate in vitro and in vivo, and elucidate the mechanism underlying its immunogenicity. This study will generate a safe, efficacious, single-dose ZIKV vaccine that will be ideally suited to affordably control explosive outbreaks, which typically affect resource-limited regions. Our platform’s antigenic superiority will result in enhanced efficacy, effectively combining the safety of replication-defective virus-like particles or nucleic acid vaccines with the antigenic superiority, and rapid, long-lived immunogenicity of live-attenuated vaccines. This platform can also be readily translated to other flaviviruses of human or veterinary importance.",,2025,VIRGINIA POLYTECHNIC INST AND ST UNIV,395583,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Characterisation of vaccine-induced immunity,2020 +P22339,1R21AI159643-01,Broad-spectrum inhibitors targeting the viral replication promoter conserved in dengue and Zika viruses,"Project Summary Zika virus (ZIKV) and dengue virus (DENV) are mosquito-borne flaviviruses that cause disease ranging in severity from mild symptoms to deadly hemorrhagic dengue fever. ZIKV was rapidly spreading five years ago to over 20 countries in South and Central America, where infections by ZIKV reached pandemic levels and threatened to expand to the southern US. The threat by DENV has increased dramatically over the last two decades as one of the worst mosquito-borne pathogens in tropical regions. To treat outbreaks of DENV in ZIKV-endemic regions, and vice versa, broad-spectrum inhibitor drugs against mosquito-borne flaviviruses would provide an efficient therapeutic approach that reduces the risk of immuno-associated exacerbation, for example in previously infected or vaccinated patients. Sequence alignment of DENV and ZIKV clinical isolates in combination with secondary structure prediction have led us to identify a conserved RNA three-way junction that serves as the replication promoter in flaviviruses. Here, we propose to identify compounds that inhibit viral replication by targeting the promoter RNA as lead candidates for the future development of DENV and ZIKV broad-spectrum therapeutics. The Specific Aims of this proposal are to 1) develop a FRET-based binding assay to assess small molecules as selective ligands of the DENV and ZIKV replication promoter RNA, 2) establish an in vitro replication initiation assay to identify promoter RNA-binding ligands as inhibitors of ZIKV replication, and 3) discover small molecules that inhibit DENV and ZIKV in cell culture by targeting the RNA 3WJ motif that serves as the viral replication promoter.",,2023,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",232977,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22340,5F31AI152460-02,Transcriptional and functional profiling of cross-reactive T cells to understand outcomes for the pathogen and host during heterologous infection,"Zika virus (ZIKV) spread explosively throughout the Americas in 2015, leaving in its wake a devastating and ever-expanding list of sequela associated with infection. Since this epidemic, substantial effort has been put forth to understand the emergence of ZIKV in the Americas, the course of disease and importantly, the correlates of protection. ZIKV is a member of the flavivirus genus which includes other arthropod-borne human pathogens such as yellow fever virus (YFV), West Nile virus (WNV), and the four serotypes of dengue virus (DENV). In addition to circulating in mosquito populations in the same geographic regions, flaviviruses share a substantial degree of genetic, and consequently antigenic similarity. This begs the question: In areas of endemic flavivirus circulation, how does immunity to one flavivirus shape immunity to the next? Moreover, how does this divergent immune restriction alter the viral swarms that replicate within the host? These questions are of great importance due to what we know about DENV. The enhanced disease seen in secondary infection with a heterologous serotype of DENV has been hypothesized to be mediated by both suboptimal cross-reactive antibody and T cell responses. The proposed research study is to define how exposure to a heterologous flavivirus shapes the transcriptional and functional T cell response to ZIKV in a mouse model of infection, and how those T cells in turn impact viral populations within the host and ultimately pathogenesis. We have shown previously that CD4+ and CD8+ T cells play important roles in protection from ZIKV disease in a mouse model of infection and were able to identify specific epitopes to which the responses are directed in this H2b-restricted model. We have also generated data showing that effector CD8+ T cells generated during infection with DENV1-4, YFV, Usutu virus, Kunjin virus or WNV functionally cross-react with at least one ZIKV CD8+ epitope, which we are terming a “pan-flavivirus” epitope. We have found that prior infection with a heterologous flavivirus results in altered phenotypic responses to this cross-reactive epitope during a subsequent ZIKV infection compared to a homologous ZIKV prime-boost challenge or a primary ZIKV challenge. One specific example of this is that cross-reactive cells derived from a heterologous infection produce far more Granzyme B relative to homologously derived cells. However, it is still unknown what drives these functional changes and how they impact protection from ZIKV-induced disease, which will be evaluated in Aim 1. More recently, it is being appreciated that different immune selective pressures can impact the viral populations that evolve within the host during infection, particularly in RNA viruses. How this observed altered T cell function during heterologous ZIKV infection alters viral quasispecies diversity within the host will be evaluated in Aim 2.",,2021,SAINT LOUIS UNIVERSITY,15229,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P22341,1R01GM139823-01A1,How flaviviruses hijack a host transmembrane protein chaperone to promote viral infection,"Dengue virus (DENV) infection is the most common arboviral disease globally, with up to 400 million infections and 25,000 deaths annually. The related flavivirus Zika virus (ZIKV) has also spread rapidly across the tropics and subtropics, and outbreaks of both DENV and ZIKV infection have now reached the continental United States. There are currently no effective antiviral agents against either virus, no DENV vaccine approved for use in the United States, and no ZIKV vaccine. Our long-term goal is to comprehensively identify and characterize the cellular pathways required for flavivirus infection, as these may represent novel targets for antiviral treatment. We and others have identified the host Endoplasmic Reticulum Membrane Protein Complex (EMC) as required for infection by multiple flaviviruses, including DENV and ZIKV. The EMC appears to function as a molecular chaperone, promoting the biogenesis of multipass membrane proteins in the endoplasmic reticulum. However, how the EMC supports flavivirus infection is unknown. Strikingly, our published findings reveal that during infection, the EMC is required by flavivirus replication by promoting the biogenesis of flavivirus NS4A and NS4B at an early post-translational step. Both proteins are non-structural multipass transmembrane proteins essential for viral replication. The objective of this proposal is to define how the EMC supports DENV and ZIKV replication. Our central hypothesis, based on strong preliminary data, is that the EMC functions as a molecular chaperone for the proper biogenesis of select flavivirus-encoded multipass transmembrane proteins. This proposal leverages the complementary strengths of an investigator with extensive experience in flavivirus-host biology (Tai), and another in ER-quality control mechanisms hijacked during viral infection (Tsai). The specific aims of the project are to (1) Define and validate the viral determinants of EMC dependence; (2) Determine the specific role of the EMC in flaviviral replication; and (3) Characterize DENV and ZIKV mutants that bypass EMC dependency. Successful completion of this project will illuminate the mechanism by which the EMC supports flavivirus infection, thereby providing insights into a novel vulnerability shared by these medically important viruses. It will also increase our understanding of other viruses that require the EMC.",,2025,UNIVERSITY OF MICHIGAN AT ANN ARBOR,356140,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22342,5K08AI150996-02,Innate Immunity of Zika Virus Infection In Human Neural Progenitors,"PROJECT SUMMARY / ABSTRACT The 2016 outbreak of Zika virus (ZIKV) in the Americas demonstrated how quickly and dramatically a mosquito-borne viral infection can affect human life. Like related flavivirus family members such as West Nile virus, ZIKV can invade and infect the central nervous system (CNS), but is unique in causing in utero infection which leads to developmental abnormalities including microcephaly. ZIKV seems to have a predilection for infecting neural progenitor cells (NPCs) and persists for months in the fetal CNS after in utero infection, which suggests an ineffective immune control of the virus. We hypothesize that impaired innate immunity in neural progenitor cells underlies increased susceptibility to infection by ZIKV and contributes to microcephaly. The innate immune system includes pattern recognition receptors (PRRs) that detect pathogens and signal through effector molecules including interferon (IFN), which drives the expression of hundreds of antiviral interferon-stimulated genes (ISGs). Using induced neural progenitor cells (iNPCs) as a model for fetal CNS development, we have identified key innate immune signals that are attenuated in neural progenitors compared to mature neurons and glia: the expression levels of retinoic acid-inducible gene I (RIG-I, a PRR that detects viral RNA); and the IFN-driven upregulation of two ISGs (IFIT1 and IFITM1). We now propose to extend these findings as follows: (1) we will define the developmental changes in expression and function of PRRs during neural differentiation using the iNPC system and an established embryonic stem cell line as a control; (2) we will use CRISPR knockout or overexpression of RIG-I in bulk iNPCs and in a cerebral organoid model to test whether insufficient RIG-I signaling underlies iNPC susceptibility to ZIKV infection and microcephaly; (3) we will perform single cell RNA-seq on ZIKV-infected neural progenitors, neurons and glia to identify differentially expressed genes and gene networks, revealing innate immune components that confer susceptibility or resistance to ZIKV; and (4) using CRISPR knockout or overexpression of IFIT1 and IFITM1 we will test the role of these proteins in limiting ZIKV infection in progenitors and cerebral organoids. These experiments will define key innate immune proteins that influence susceptibility or resistance to ZIKV, identifying therapeutic targets to protect the fetal brain during ZIKV infection. Dr. Stokes’ development plan builds on a background in neurosciences with coursework and hands-on training in immunology, neural stem cells, and bioinformatics. The proposal establishes a mentoring committee including faculty in immunology, neurosciences, and infectious disease to provide guidance and career development. A K08 award will allow Dr. Stokes to make maximal use of UW’s extensive scientific resources to achieve scientific independence, advancing his career goal to develop therapeutic interventions that protect neural function from injury during viral encephalitis.",,2025,UNIVERSITY OF WASHINGTON,196069,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2020 +P22343,5K99DE028573-03,Molecular regulatory mechanism of Zika virus-induced intracranial calcifications,"Project Summary/Abstract: The number of vector-borne disease cases in the US has tripled over the past decade and these pathogens including mosquito-borne Zika virus (ZIKV) remain an apparent threat to general public health. The ZIKV outbreaks in the Americas and Southeast Asia is a major global health concern, largely due to the association with fetal craniofacial abnormalities and malformations, resulting from prenatal infection. Although ZIKV infection during pregnancy is casually associated with microcephaly, it is important to note that intracranial calcification is the most frequent abnormality present in ZIKV-positive babies. In fact, Magnetic Resonance Imaging study of Brazilian large ZIKV-positive baby cohort reported the intracranial calcifications as the most common clinical observations. While calcification occurs in soft tissues, the abnormal deposition of calcium in brain not only severely affects motor function, speech ability, and vision, but also causes seizures. Despite the growing clinical evidences of ZIKV-induced calcifications and their potential dire outcomes, however, the etiology and molecular mechanisms of ZIKV-induced brain calcification remain elusive. My preliminary observations in ZIKV human fetal brain specimens showed that high level of calcium deposits was localized with virus-infected perivascular cells. Intriguingly, ZIKV-infection of brain perivascular and osteogenic precursor cells robustly induced calcifications in vitro. Surprisingly, the induction of calcification was lineage-specific to the Asian ZIKV strains, but not to the African ZIKV strains. African ZIKV strains rapidly replicated, inducing cell death, while Asian ZIKV strains persistently replicated, leading to aberrant calcium deposition. Surprisingly, ZIKV expression library screen showed that NS3 protease was sufficient to induce calcification. Based on these preliminary data, I hypothesize that ZIKV targets specific host brain perivascular cells and utilizes NS3 protease to induce intracranial calcifications, which ultimately contributes to virus-associated congenital abnormality. Herein, I seek to address the following questions: (i) which host cells are targeted for ZIKV-induced calcifications, and (ii and iii) which and how ZIKV NS3 protease triggers abnormal calcification during infection. This proposal is highly innovative and translational, and potentially shed new insights to ZIKV-induced intracranial calcification that is the most frequent abnormality present in virus-infected babies.",,2022,CLEVELAND CLINIC LERNER COM-CWRU,94042,Viruses,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P22344,1R01EY032149-01,Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection,"PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pathology, including loss of foveal reflex and macular pigment mottling, chorioretinal scarring, and macular atrophy. ZIKV has become endemic and local transmissions in the USA have been reported previously. The long-term effects of structural damage on vision, as well as the pathogenic processes of congenital ZIKV eye diseases are beginning to be understood. The signaling pathways governing normal eye development, which are dysregulated during ZIKV infection, are not well characterized. We recently carried out a series of experiments by establishing a ZIKV infectious ocular cell culture system and mouse models to understand the structural and molecular perturbations. For successful replication, viruses have evolved various strategies to evade innate immune response as well as to enhance the availability of cellular metabolites required to meet the heightened energy demand for viral genome synthesis. We found that the AMPKα, a cellular master energy sensor, is activated in the ZIKV-infected retinal cells. Moreover, pharmacological activation of AMPK resulted in attenuated ZIKV replication. Another interesting finding is that the YAP/TAZ factors in the tumor suppressor Hippo/SWH signaling pathway were induced early on, but degraded at later stage of ZIKV infection in RPE cells. Silencing YAP/TAZ resulted in reduced ZIKV replication. Since the energy sensor AMPK and Hippo signaling pathways control key cellular processes, including host antiviral responses, it is critical to understand the fundamental mechanism of these two pathways deregulation. We hypothesize that ZIKV modulates AMPK and Hippo signaling pathways in ocular cells to 1) increase intracellular metabolic resources, and 2) inhibit TBK1 to antagonize antiviral defense. These molecular changes can be orchestrated through viral coded factors resulting in the pathogenesis of ocular cell injury. The following specific aims will be investigated. Aim 1 focuses on systematically evaluating the role of AMPK- Hippo signaling on regulating antiviral response to ZIKV infection in RPE cells. The cross talk between these pathways will be investigated at the YAP/TAZ level. Pharmacological activation/inhibition, and gene knockout approaches in RPE cells will be carried out. Aim 2 is designed to elucidate the effect of ZIKV on Hippo and AMPK signaling pathways during retinal development. Human iPSC-derived 3D-retinal cup organoids will be used to investigate the link between retinal development and ZIKV-mediated deregulation of these key pathways. The ZIKV-encoded virulence factors regulating these pathways will be characterized. Aim 3 is to determine the effect of RPE-specific ablation of AMPK, TBK1, and Hippo signaling on the pathogenesis of ZIKV-induced chorioretinal atrophy in mice. This proposed study would yield novel insights into the pathogenesis of ZIKV in ocular diseases and identification of potential therapeutic targets.",,2024,UNIVERSITY OF CALIFORNIA LOS ANGELES,534349,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2021 +P22345,5R01AI148477-02,Implications of sequential bloodmeals on arbovirus transmission by mosquitoes,"Brackney & Armstrong Abstract: Aedes aegypti is the primary vector for a number of human pathogens, including dengue virus (DENV; Flaviviridae, Flavivirus), Zika virus (ZIKV; Flaviviridae, Flavivirus), chikungunya virus (CHIKV; Togaviridae, Alphavirus) and yellow fever virus (YFV; Flaviviridae, Flavivirus), all of which present a continued threat to human health worldwide. Understanding the endemic and epidemic risk of these arthropod-borne (arbo-) viruses is critical to the success of public health preparedness and intervention. One key entomological parameter informing risk estimates is vector competence (how able a mosquito is to become infected and transmit an arbovirus; VC). Quantifying the competency of local vector populations can help inform the risk that any one pathogen poses to a given community. This is often quantified in the laboratory by exposing populations of local mosquitoes to an infectious bloodmeal and harvesting tissues at set time-points post infection. While informative, this approach often fails to consider the biology and behavior of the vector mosquito. For example, it is known that wild Ae. aegypti mosquitoes will imbibe several bloodmeals over the course of a traditional laboratory-based vector competence study (e.g. bloodmeal every two to three days). To address these shortcomings, we recently began examining the effects that multiple blood feeding episodes have on the competency of Ae. aegypti mosquitoes for ZIKV. Our preliminary findings reveal that providing a second non-infectious bloodmeal to ZIKV infected Ae. aegypti mosquitoes enhances viral escape from the midgut and significantly shortens the duration between mosquito acquisition of ZIKV to transmission. In this application we will examine the effects that multiple bloodfeeding episodes have on arbovirus infection of and transmission by vector mosquitoes. Specifically, we will be 1) testing this phenomenon in other virus-vector pairings, 2) evaluating the role of the midgut basal lamina in mediating the double-feed phenotype and 3) determining if similar processes are mediating the ability of arboviruses to infect ovarian tissue and be transmitted vertically.",,2025,CONNECTICUT AGRICULTURAL EXPERIMENT STA,293370,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Animal and environmental research and research on diseases vectors | Pathogen: natural history, transmission and diagnostics","Vector biology | Pathogen morphology, shedding & natural history",2020 +P22346,5R21AI146464-02,Evaluation of in vitro and in vivo efficacy of glycan-based compounds against flavivirus endothelial permeability and vascular leak,"ABSTRACT Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne viruses that are major medical and public health problems worldwide. DENV causes the most prevalent mosquito-borne viral disease of humans, and severe cases manifesting vascular leakage can be fatal. The related Zika virus (ZIKV) recently caused explosive epidemics across the Americas and has been associated with congenital birth defects and Guillain-Barré syndrome. Despite their substantial worldwide morbidity and mortality, no therapeutic agents exist for treatment of dengue or Zika. Nonstructural protein 1 (NS1) is a flaviviral protein that participates in viral RNA replication and in its secreted form plays important roles in host immune evasion and viral pathogenesis. We and others recently described novel roles for NS1 in directly triggering endothelial barrier dysfunction and inducing inflammatory cytokine production from human immune cells, contributing to vascular leak in vivo. In this proposal, we will evaluate the in vitro and in vivo efficacy of glycans against NS1-mediated pathogenesis, as well as against DENV and ZIKV infection in vivo. We have developed multiple methods to study DENV and ZIKV pathogenesis based on characterization of NS1-induced endothelial barrier dysfunction in vitro (e.g., hyper- permeability, disruption of the endothelial glycocalyx-like layer [EGL]) and in vivo, using murine models of virus- and NS1-induced disease with vascular leakage. Our preliminary results showing that a sulfated derivative of β- glucan from Agaricus brasiliensis fungus (FR-S) has a protective effect in vitro and in vivo against DENV NS1- induced endothelial hyperpermeability are promising. We have also shown that FR-S has anti-DENV and anti- ZIKV activity in vitro. In collaboration with Dr. K. Godula (UC San Diego) we determined that specific synthetic GAG-mimetic molecules efficiently bind to flavivirus NS1. Given the contribution of NS1 to flavivirus pathogenesis and our preliminary results, we hypothesize that glycans inhibit NS1-induced EGL degradation and vas- cular leakage in vivo as well as viral infection and have potential as novel treatment modalities for dengue and Zika. The approach is innovative in that we target inhibition of severe disease manifestations, in addition to antiviral activity. Aim 1 will select the most promising inhibitor(s) of NS1-induced pathophysiological pathways of DENV and ZIKV based on prevention of endothelial dysfunction in vitro. We will screen 27 glycans, including FR and FR-S, 4 GAG-mimetics, sulodexide, and 20 cyclodextrin analogues (in collaboration with Dr. T. Sohajda, CycloLab), for their ability to prevent NS1-induced hyperpermeability. Aim 2 will investigate the in vitro mechanism of action of prevention of endothelial dysfunction by the selected compounds. Aim 3 will evaluate the therapeutic potential of the most active compounds against DENV and ZIKV NS1- and virus-induced vascular leak, morbidity, and mortality in vivo. Overall, this proposal address- es a critical need, identifying novel therapeutic strategies against two major flaviviral diseases, by developing glycan-based compounds that target both the virus and pathophysiological consequences of infection.",,2023,UNIVERSITY OF CALIFORNIA BERKELEY,200000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +P22347,1R21AI151475-01A1,Identification and validation of Zika virus receptor(s) in the midgut lumen of Aedes aegypti,"SUMMARY The central goal of this project is to identify Zika virus (ZIKV) receptor(s), generation ZIKV transmission incompetent transgenic mosquitoes that lack the receptor-encoding gene and identification of novel transmission blocking vaccine candidate(s). Transmission of arthropod-borne viruses (arboviruses) causes widespread and debilitating diseases across the globe. In the absence of effective licensed vaccines or therapeutic treatments of arboviruses, including ZIKV, control at the vector level is the most effective method to ameliorate the burden of these viruses. Before these viruses can be transmitted to humans, they must first infect the mosquito following a blood meal. Thus, investigations to understand ZIKV-mosquito interactions are of critical importance. In this proposal, we will identify specific molecules in the Aedes aegypti mosquito midgut that act as receptors and facilitators for ZIKV binding and establishment of infection. Identified candidate receptors will be validated in vivo by genetic ablation using CRISPR/Cas9 gene editing and subsequent oral challenge with an infectious ZIKV blood meal. Data generated in this study will assist in 1) the development of effective disease control measures, e.g. via the generation of transgenic mosquitoes that lack the receptor-encoding gene and would be incompetent for ZIKV transmission; and 2) identification of ZIKV receptor molecules in the mosquito midgut will provide new insights into the basic biology and molecular mechanisms underpinning the vector competency and mosquito- arboviral pathogen interactions. The proposed experiments are also significant because they provide the groundwork for future experiments that will determine whether the same receptor(s) is used by other arboviruses and other mosquito species.",,2023,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,226756,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22348,5R21AI149112-02,Targeting Regulatory RNA elements in the Zika Virus,"Project Summary Zika virus (ZIKV) is a positive sense strand RNA virus of the mosquito-borne flaviviruses that recently caused a global epidemic. ZIKV infection can result in the induction of several neurological disorders, including Guillain- Barré syndrome and fetal microcephaly. Recently, a highly conserved noncoding RNA element in the 3' un- translated region of the ZIKV RNA genome called the Xrn1-resistant structure (xrRNA1) was identified that stalls the host exonuclease (Xrn1), allowing the virus to produce subgenomic flaviviral RNAs (sfRNA) directly connected to viral pathology. The crystal structure of xrRNA1 reveals that it adopts an unusual three- dimensional structure composed of a three-way junction stabilized by a pseudoknot, with the 5′-end segment threading through a helical `ring' formed by the three-way junction. This unusual structure has been shown to confound the helicase activity of Xrn1 and promote sfRNA formation. Mutations that disrupt key structural fea- tures formed by highly conserved nucleotides severely decrease Xrn1 resistance and sfRNA formation during infection. xrRNA1 is an ideal drug target in the ZIKV RNA due to the unlikelihood of generating resistance mu- tations and the presence of a druggable pocket with unique structural features that has the potential to selectively bind small molecules. This project will screen xrRNA1 against ~1 million small molecules to identify inhibitors of ZIKV replication that specifically target and disrupt the structure of xrRNA1 and thereby inhibit pro- duction of sfRNA, impacting pathogenesis by decreasing virulence. This will be accomplished using a new hybrid in silico/in vitro RNA-small molecule screening technology (RNA targeting using Experimentally-Based Ensembles for Ligand discovery” or REBEL) that makes it possible to widen RNA screens to millions of mole- cules and to create sub-libraries that are enriched with bioactive and selective RNA-targeting compounds. Aim 1 will use REBEL to identify compounds that bind and modulate the structure of xrRNA1. The one thousand top hits will be subjected to experimental screening for xrRNA1 binding and inhibition of sfRNA formation using NMR spectroscopy and in vitro sfRNA formation assays. In Aim 2, hits from in vitro assays will be tested for anti-ZIKV and anti-DENV activity and toxicity in cellular based assays. If successful, this work will identify promising leads for the development of antiviral therapies for treatment of ZIKV and may lay the foundation for a new strategy to target pathogenic flaviviruses in general.",,2022,DUKE UNIVERSITY,193566,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P22349,1R01AI146049-01A1,Anchimerically Activatable Anti-Zika/Dengue ProTides,"Arboviruses such as, Dengue (DENV) and Zika (ZIKV), have been associated with several global epidemics. DENV infections can result in a mild fever to potentially fatal dengue shock syndrome, dengue hemorrhagic fever and death, while ZIKV infections can result in congenital microcephaly and the development of autoimmune diseases. Initial clinical manifestation of DENV and ZIKV disease are similar and co-infections have been reported. Most challenging, DENV and ZIKV are known to co-circulate, increasing the probability of co-infections, and thus the potential for severe disease. Consequently, since there is no effective vaccine or form of treatment for either virus, the development of anti-ZIKV and anti-DENV therapeutics is an urgent unmet medical need. Over the past decade prodrugs of nucleotides, referred to as ProTides, have been found to have potent antiviral activity. The anti-hepatitis C virus (HCV) drug sofosbuvir (FDA approved 2013) is the most notable ProTide success, since its use in combination therapy can clear Hepatis C virus infections. Recently, a similar ProTide, remdesivir, has been approved by the FDA, Japan, the European Union an Australia for the treatment of severe SARs-CoV-2 infections by intravenous injection. Carboxyesterase-anhydride-HINT1 (CAH) ProTides, such as sofosbuvir and remdesivir, utilize a four step activation process based on initial esterase hydrolysis, carboxylic acid nucleophilic attack at the phosphorous and release of phenol, followed by mixed anhydride chemical hydrolysis, and finally phosphoramidate hydrolysis by hHINT1. Unfortunately, although they can be dosed intravenously, due to high first pass metabolism, CAH-Protides are limited in their use as oral drugs to viral hepatitis. Furthermore, due to the high carboxyesterase activity of rodent plasma, it has been difficult to carry out pre-clinical studies with rodents and translationally relevant dosages of CAH-ProTides. To address the inherent issues surrounding current ProTide approaches, our group has designed an alternative ProTide approach, we refer to as anchimerically HINT1 activated proTides (AHA-ProTides). Our laboratory has demonstrated that AHA-proTides can be designed that are stable, orally bioavailable, cell permeable and dependent on HINT phosphoramidate hydrolysis. Recently, we have also demonstrated that AHA proTides can be prepared with enhanced potency against DENV and ZIKV. Consequently, we propose to the design and develop anti-DENV and anti-ZIKV AHA ProTides that can serve as advanced lead compounds for the potential treatment of both DENV and ZIKV disease.",,2026,UNIVERSITY OF MINNESOTA,670946,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Congenital Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22350,5F31AI154840-02,Investigating IRG1-driven regulation of flavivirus-induced neuroinflammation,"Project Summary/ Abstract The goal of this proposal is to investigate the anti-viral and anti-inflammatory roles of the metabolite, itaconate, in the central nervous system (CNS), during Zika virus (ZIKV)-encephalitis. ZIKV is an emerging mosquito-borne flavivirus of global concern. In the recent epidemic, ZIKV infection in adults was associated with a range of neurological disorders such as Guillain-Barré syndrome, encephalitis, and Myasthenia Gravis. These pathologies are largely thought to be a consequence of ZIKV tropism for neurons and neural progenitor cells. As such, there has been an intense effort to study ZIKV-immunity in the CNS. Recently our lab discovered a neuron intrinsic anti-viral defense mechanism against ZIKV infection, whereby infected neurons induce the expression of the mitochondrial enzyme IRG1. Here, IRG1 and its metabolic product itaconate, remodel neuronal metabolism to inhibit viral replication. Our study also found that Irg1-/- mice are highly susceptible to infection, but whether this phenotype is strictly due to the role of neuronal-itaconate or concurrent involvement of glia- derived itaconate remains unknown. Itaconate has garnered significant attention as an immunomodulatory metabolite in myeloid cells. Specifically, itaconate has been shown to be an indispensable immunoregulatory metabolite necessary to limit inflammation in bacterial models of infection. Moreover, published work has shown itaconate to be secreted by macrophages, implying the potential for itaconate to act in a non-cell-autonomous manner. Preliminary data generated in our lab using a model of ZIKV-encephalitis revealed that mice lacking Irg1 have significant leukocyte infiltration in the brain compared to WT mice, data supporting the anti-inflammatory role of itaconate. However, this effect was not a result of increased inflammatory gene transcription in ZIKV-infected neurons, implying a neuron-extrinsic source of itaconate necessary to regulate neuroinflammation. Notably, resting microglia, the resident macrophages of the CNS, express high levels of Irg1, suggesting to us that this cell type might also be a key source of itaconate during ZIKV-infection. Therefore, based on preliminary data, we hypothesize that microglia-derived itaconate acts as an antiviral and anti-inflammatory mediator during ZIKV- encephalitis. Specifically, we hypothesize that microglia-derived itaconate signals to neurons in trans to limit both viral replication and neuroinflammation in a non-cell-autonomous manner.",,2022,UNIVERSITY OF WASHINGTON,23940,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +P22351,5R41AI152904-02,Vaccination against Zika virus infection using mosquito NeSt1 protein,"Arthropod-borne viruses (arboviruses) present a substantial threat to human and animal health worldwide. They are transmitted by hematophagous arthropods, in which mosquitoes are one of the main transmitters. The mosquito specie, Aedes aegypti, is the primary mosquito vector of several widely spread arboviruses as zika, dengue or West Nile viruses. Mosquitoes transmit these pathogens by inoculating virus-infected saliva into host skin during probing and feeding. This saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feed. Some of these proteins are known to enhance infectivity and pathogenesis in Zika and other arboviruses by modulating immune responses, and the development of blocking therapies against them could be a good approach to reduce infectivity and pathogenesis in the host. In addition, focusing on mosquito proteins as vaccine targets can overcome the problems associated with the use of viral antigens as a vaccine targets, due to their high variability. In this proposal, we will develop a novel transmission-blocking vaccine against Zika virus (ZIKV) by targeting A. aegypti bacteria responsive protein 1 (AgBR1) and A. aegypti neutrophil stimulating factor 1 (NeSt1) salivary gland protein. Using a yeast surface display screen, we identified a set of A. aegypti salivary proteins that react with sera from mice repeatedly bitten by A. aegypti mosquitoes. Passive immunization with antiserum against two of these proteins, AgBR1 and NeSt1, resulted in significantly more survival in mice infected with ZIKV by mosquito bite. Simultaneous passive immunization with both antisera demonstrated a synergy resulting in higher survival than expected from the individual treatments. Based on these results, in this proposal we intend to carefully examine the protective effects of blocking the mosquito AgBR1 and NeSt1 proteins in preventing severe mosquito-borne ZIKV infection in mice. We will develop a strategy for actively immunizing mice against both proteins towards the development of a vaccine for use in humans. The success of this approach also offers a functional paradigm for developing vaccines against other flaviviruses and other arthropod- borne pathogens of medical importance.",,2023,"L2 DIAGNOSTICS, LLC",293886,Animals | Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Vector biology",2020 +P22352,1R01NS117149-01A1,Leveraging Zika virus and the immune system to treat glioblastoma,"PROJECT SUMMARY Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2 years. Despite aggressive therapy, most GBMs reappear within 6 months. A major reason for this outcome is because GBM stem cells (GSCs) are resistant to existing therapies. Currently, no treatment consistently kills these highly resistant cells. However, the Zika virus epidemic has provided us with a new approach to eradicate GSCs. ZIKV targets normal stem cells in the developing fetal brain, yet has minimal effects on differentiated neurons or the adult brain. Since GSCs share properties with neural stem cells, we investigated whether the natural honing and lytic activity of ZIKV could be harnessed to target and kill GSCs. We published the first use of ZIKV to kill GSCs. We showed that ZIKV kills GSCs in tumors removed from patients, with minimal impact on non-GSC tumor cells, called differentiated GBM cells. Importantly, normal human brain cells were not affected by ZIKV. After intracranial treatment with ZIKV, mice harboring gliomas survived more than twice as long as untreated mice and, in some cases, treated mice were long-term survivors. In addition to the resistance of GBM stem cell to chemoradiation, GBM is the hallmark example of an immunotherapy-resistant tumor. Importantly, we found that in vivo, ZIKV treatment reduces tumor size and extends survival beyond that expected for only anti-GSC effects. This suggested that ZIKV killing of GSCs may trigger an immune response against the remainder of the tumor. In more recent studies, we have found that CD8+ T cells are required for the efficacy of ZIKV as an oncolytic therapy in vivo. Our central hypothesis is that ZIKV elicits an anti-tumor immune response that could be made even more effective by combining it with existing immunotherapies. Aim 1 will determine how CD8+ T cells promote tumor clearance after ZIKV and Aim 2 will determine whether ZIKV can be combined with immunotherapy or standard-of-care for GBM to improve outcomes. Our long-term goal is to develop a new treatment for GBM by leveraging the immune system response to ZIKV.",,2025,WASHINGTON UNIVERSITY,389854,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,,,2020 +P22353,1R21AI157147-01A1,Three-dimensional human epithelial cultures as a model for evaluation of flavivirus-host interactions driving infection in the skin,"PROJECT SUMMARY Zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV) all cause severe human disease as a result of their widespread mosquito-borne transmission. While these flaviviruses share a common primary site of infection in the dermis, they disseminate to varying secondary sites of infection with highly divergent clinical outcomes. We propose that discrepancies in early virus-host interactions among ZIKV, DENV, and WNV are responsible for these differences in disease; however, there is a gap in our knowledge of the molecular mechanisms responsible. Elucidation of distinct virus-host interactions occurring at the initial infection site is thus key to understanding how these viruses establish productive infections in the skin and elsewhere. The proposed research will establish organotypic epithelial cultures as a genetically tractable and immunocompetent 3D human skin model of flavivirus infection, to be used for virus-host interaction studies. We will expand on the current model commonly used to study DNA viruses, typically comprised solely of human fibroblasts and keratinocytes, with the addition of human skin-resident dendritic cells and macrophages, to accurately recreate natural flavivirus infection in the skin. Additionally, we will incorporate mosquito saliva, which includes immunomodulatory and anti-inflammatory proteins, into the virus inoculum to further recapitulate the molecular events occurring at the primary site of flavivirus infection. We will determine individual infection conditions for ZIKV, DENV, and WNV, and evaluate cell tropism and host responses with each virus. Once established, we will employ this 3D human skin model to evaluate the role of the host ribonuclease L (RNase L) protein during ZIKV infection in the skin, which will validate this system for flavivirus-host interaction studies. While antiviral RNase L activity is well described, we have recently discovered proviral RNase L activity during ZIKV infection. In contrast, we observed canonical antiviral RNase L activity during DENV and WNV infections. These studies were performed in 2D monolayer culture systems with immortalized cell lines, therefore we will use our 3D skin model containing primary cells to test the hypothesis that RNase L plays a role in ZIKV cell tropism and spread in the skin in a more relevant system. We will use CRISPR-Cas9 gene editing to delete RNase L from the different skin cells comprising epithelial cultures, and subsequently generate RNase L-deficient skin cultures for infections with ZIKV, DENV, or WNV. We will assess effects of RNase L deletion on infection and spread of the different flaviviruses in the skin, as well as how host responses are impacted. The proposed studies will characterize the role of RNase L as an important host factor repurposed by ZIKV during infection in the skin. Furthermore, this project will establish organotypic epithelial cultures as an exciting new human model amenable to gene editing which will facilitate inquiries of arbovirus-host interactions and host responses at the common primary infection site of the skin.",,2023,UNIVERSITY OF PENNSYLVANIA,203073,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease models | Disease pathogenesis",2021 +P22354,5R21AI149118-02,The role of hemocytes in mosquito arbovirus infection,"PROJECT SUMMARY Mosquito arbovirus transmission causes hundreds of millions of human infections every with significant disease morbidity and mortality outcomes. However, despite the requirements of the mosquito host for virus replication and transmission, our understanding of these mechanisms is poorly understood. This includes the role of mosquito immune cells, or hemocytes, which may have both positive and negative influences on virus replication. Building on our expertise in hemocyte biology and host-pathogen interactions, we now look to examine the role of mosquito hemocytes on dengue (DENV) and Zika virus (ZIKV) infection. Using a chemical genetics approach, we provide preliminary data demonstrating our ability to deplete phagocytic immune cell populations in Aedes aegypti, which serve as the basis of our proposed experiments. Therefore, the studies in this proposal will examine the contributions of phagocytic immune cells on DENV and ZIKV infections, and explore the mechanisms by which these cells may mediate systemic RNAi responses in the mosquito host (Aim 1). In addition, we will also explore potential roles of hemocytes as a secondary site of virus amplification that may increase viral titers and aid dissemination to increase the likelihood of transmission (Aim 2). Together, we expect that the results of this study will provide new information into the mechanisms of virus replication in the mosquito host and define the integral role of hemocytes in mosquito vector competence to arbovirus infection.",,2023,IOWA STATE UNIVERSITY,181208,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22355,1F31AI154695-01A1,Effect of an Fc Gamma Receptor Polymorphism on Antibody-Dependent Enhancement of Zika Virus Infection,"PROJECT SUMMARY Antibody-dependent enhancement (ADE) is a phenomenon by which antibodies raised in response to a primary infection cross-react to a similar pathogen during a subsequent infection, resulting in increased viral load and severity of disease. ADE of Zika virus (ZIKV) infection by preexisting DENV antibodies has been hypothesized to play a role in the severe adverse pregnancy outcomes observed following congenital ZIKV infection. ADE is mediated by interactions between virus-bound IgG antibodies and Fc gamma receptors (FcRs) on host cells. In humans, a nonsynonymous single nucleotide polymorphism (SNP) in FCGR2A, rs1801274, results in an amino acid change at site 131 from arginine (Arg131) to histidine (His131) in the IgG-binding region of FcRIIA. Previous work in vitro has shown that cells expressing the His131 receptor variant bind human IgG1 and IgG2 with significantly higher affinity than those expressing the Arg131 receptor variant. We hypothesize that individuals homozygous for the high affinity His131 allele will be at greater risk for ADE of viral infection than individuals homozygous for the low affinity Arg131 allele. In this application, we will assess the effect of this SNP on ADE of ZIKV using cell lines derived from K562 cells that are homozygous for the Arg131 or His131 allele and primary human monocytes that will be stratified by genotype (Aim 1). We have also generated IgG subclass switch variants of a flavivirus-reactive monoclonal antibody that we will use to assess the role of each IgG subclass in mediating ADE of ZIKV through the different FcRIIA variants using His131 and Arg131 homozygous K562 cell lines, primary human monocytes, and Hofbauer cells isolated from full term human placentas (Aim 2). A comprehensive understanding of host genetic factors that affect susceptibility to ADE, including those described in this proposal, may help to identify populations at increased risk of developing severe disease as a result of ZIKV infection, particularly among pregnant women. The proposed project provides an excellent opportunity for training that encapsulates traditional virology and immunology techniques, professional development, and mentorship that will support the applicant’s growth as an independent academic scientist.",,2024,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,44436,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2021 +P22356,1R01AI155735-01,Multiplexed Detection of Mosquito-Borne Viruses at the Point-of-Care,"Project Summary Dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), and Mayaro virus (MAYV) are all mosquito-borne RNA viruses. They are public health concerns because (1) DENV and CHIKV cause hundreds of millions of infections each year, with significant burdens in affected areas, (2) the outbreak of ZIKV in Brazil in 2015/2016 caused anxieties to general population due to its association with microcephaly of newborns, and (3) MAYV emerged in Central and Southern America recently and has the potential for epidemic spread. Because these virus infections have virtually identical clinical presentation and they often circulate concurrently, it is important to have a point-of-care (POC) testing platform to accurately identify virus infection for clinical management of patients, including different complications from these viruses. According to the Centers for Disease Control and Prevention (CDC), the current methods authorized for assessing DENV, ZIKV, and CHIKV infections include reverse transcription polymerase chain reaction (RT- PCR) assay and enzyme-linked immunosorbent assay (ELISA). However, these assays are carried out in laboratories, not at POC in a clinic or in an infected field. It is also important to note that virus infection can cause asymptomatic infections, up to 80% of ZIKV patients, 50% of DENV patients, and 28% of CHIKV patients, respectively. As a result, POC testing in the field will be more valuable for screening asymptomatic patients and monitoring possible virus transmission than a laboratory test because only symptomatic patients go to hospitals or clinics for seeking medical help or to be screened. To address the need, we propose to develop a POC diagnostic platform called Valve-enabled Lysis, paper- based RNA Enrichment, and RNA Amplification Devices (VLEAD). VLEAD will integrate sample preparationâ€Â"" including virus lysis and RNA enrichmentâ€Â""with nucleic acid amplification for simultaneous detection of these viruses. To achieve the goal, we aim to (1) develop multiplexed VLEAD for simultaneous detection of ZIKV, DENV, CHIKV and MAYV; (2) optimize VLEAD using various samples and compare the suitability of the device for urine, saliva and blood samples; and (3) validate VLEAD using clinical samples and compare VLEAD with the benchmark methods including conventional RT-PCR. The significance of the research lies in the following aspects. First, these mosquito-borne RNA viruses are a public health concern. An accurate and sample-to-answer virus detection platform at POC will be useful for clinical care and patient management. Second, a large percentage of these virus infections are asymptomatic, thus a non-invasive POC platform would be very beneficial for screening the general population in the infected area and monitoring virus transmission. Third, the VLEAD platform can be adapted for detecting other pathogens of interest, with a potential to have more societal impacts.",,2025,UNIVERSITY OF FLORIDA,366660,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P22357,1R21AI156575-01A1,Global effects of flavivirus sfRNA on translation determined by ribosome profiling,"Flaviviruses include many serious pathogens such as Zika, dengue, West Nile, and yellow fever viruses. In infected cells these viruses produce abundant, noncoding, short flavivirus RNAs (sfRNAs) that comprise most of the ~500 nucleotide 3’ untranslated region of the viral genome. These novel viral RNAs have been shown recently to interact with numerous host proteins and inhibit translation (protein synthesis) of certain genes of the innate immune system. Thus, virus strains that produce high levels of sfRNA are more pathogenic, and mutants that produce no sfRNA are so mild as to be promising vaccine candidates. However, a picture of how sfRNA globally affects translation of cellular mRNAs is lacking. The Zika virus (ZIKV) epidemic of 2014-16 resulted in frighteningly frequent cases of microcephaly and other developmental and neurological disorders caused by exposure to ZIKV in utero. In addition to inhibiting the immune response, ZIKV sfRNA inhibits Fragile X Mental Retardation Protein (FMRP), a key translational regulator of neurological development. Thus, this knowledge of the global effects of ZIKV sfRNA on host translation could contribute to future research on understanding how this virus manipulates the host and causes disease. Method: We will employ the transformative method of ribosome profiling (RiboSeq) to sample the level of translation across the entire population of mRNAs in the cell in order to identify genes that are translationally up- or down-regulated in the presence of sfRNA, either alone, or in the context of replicating ZIKV. RiboSeq - a modification of high-throughput mRNA sequencing (RNAseq) - reveals only the fragments of mRNAs that are protected by translating ribosomes. The number of reads of ribosome-protected fragments from a given mRNA is proportional to how actively that mRNA is translated. This highly informative method has been applied only sparingly to flaviviruses and, to our knowledge, never to determine specifically the effects of sfRNA, a known translational regulator. We will also develop new statistical methods to improve on current imperfect approaches for calculating significance of changes in translational efficiency of mRNAs in response to a treatment. Finally, we will use a variety of bioinformatics tools to identify common structural features of mRNAs whose translation efficiencies are similarly affected by sfRNA. Expected Outcomes. Identification of genes whose translation is affected by sfRNAs will reveal potential genes and genetic pathways that facilitate - or defend against â€Â"" ZIKV infection. These can be the focus of future studies by us and others to determine their role and regulation in virus infection, the immune response, or possibly neurodevelopmental disorders. Moreover, these results may reveal new ways of regulating translation. This research can benefit human health by informing rational design of vaccines or antivirals targeting ZIKV and other flaviviruses, and by providing better understanding of control of protein synthesis by RNA.",,2023,IOWA STATE UNIVERSITY,174750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22358,5U24AI152170-02,"Multiplex serological assays to support arbovirus diagnosis, surveillance and vaccines","Abstract At a global level, ongoing ecological, environmental and demographic changes favor the survival and expansion of several mosquito and tick species that transmit arboviruses. Aedes mosquito species that thrive in urban environments created by humans are responsible for epidemics of several flaviviruses [dengue virus (DENV) serotypes 1, 2, 3, 4; Zika virus (ZIKV); yellow fever virus (YFV)] and alphaviruses [chikungunya virus (CHIKV) and Mayaro virus (MAYV)]. Laboratory-based diagnosis and surveillance for arboviruses is difficult because most infected individuals are asymptomatic or develop a mild undifferentiated febrile illness. Serological assays have been developed for the detection of recent or past arboviral infections, but the utility of these assays is severely limited by antibody cross reactivity between related viruses. For example, when ZIKV emerged in many regions of the Americas where greater than 80% of the population was dengue-immune, with current serological assays, it was difficult, if not impossible, to identify infected individuals or monitor the spread of ZIKV at a population level, and likewise to now detect new DENV infections in areas that experienced intense ZIKV epidemics. Our studies over the past 10 years demonstrate that people exposed to flavivirus infections reliably develop antibodies to epitopes that are unique to each flavivirus as well as cross-reactive antibodies. Using our discoveries about the location of immunodominant virus type-specific epitopes, we have produced novel recombinant antigens and demonstrated their utility for the type-specific diagnosis of arboviruses. Under Specific Aim 1 of this proposal, we will build on these discoveries to develop a sample-sparing, microsphere bead-based multiplex assay for the type-specific and sensitive detection of recent or past arbovirus infections. Our initial studies will focus on 8 arboviruses transmitted by Aedes aegypti and Aedes albopictus mosquitos because these viruses share a similar ecology and co-circulate in the same human populations. At a second stage, we will expand the coverage of the assay to detect infections with other arboviruses transmitted by other mosquito species and ticks. Several tetravalent DENV and ZIKV vaccines are currently being evaluated in human clinical trials. While vaccine developers have relied on neutralizing antibodies as a correlate of protection, recent results from clinical trials demonstrate that neutralizing antibodies alone are a poor correlate of vaccine safety and efficacy. We have identified flavivirus type- and epitope-specific antibody responses that are better predictors than neutralizing antibodies of vaccine safety and efficacy. Under Specific aim 2 of this proposal, we will develop a sample-sparing microsphere-based assay for the detection of epitope-specific vaccine-induced antibody responses that are correlated with protective immunity to each of the DENV serotypes and ZIKV. The technological advances and products from this proposal will enhance our ability to efficiently monitor arbovirus infections at the individual and population levels and also support the development of arbovirus vaccines.",,2025,UNIV OF NORTH CAROLINA CHAPEL HILL,413630,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +P22359,5R01AI143850-04,Defining the Role of West Nile Virus-Host Protein Interactions in Evading Antiviral Immunity,"Project Summary West Nile virus (WNV) is an emerging, neurotropic virus of the Flavivirus genus that is transmitted to humans via infected mosquitoes. Flaviviruses include globally important pathogens, such as dengue (DENV) and Zika (ZIKV) virus, which infect hundreds of millions yearly. Currently, there are no specific antiviral treatments for any flavivirus. Given the spread of flaviviruses across the globe and the dearth of options to prevent or treat them, it is imperative that we develop a better understanding of host processes that impact infection. We used affinity purification and mass spectrometry to identify the physical interactions that occur between WNV and host proteins. In collaboration with Nevan Krogan, we utilized data from parallel studies of DENV and ZIKV to focus on host proteins targeted by multiple flaviviruses. We discovered 259 high-confidence WNV-interacting host proteins; of those, 49 host proteins interacted with the analogous viral protein in either DENV or ZIKV. This analysis revealed that the most significant overlap was for capsid- and NS5- interacting proteins. To define the shared interactors that are important for infection, we employed an RNAi screen in the context of WNV, DENV and ZIKV infection. We found 23 factors that impacted WNV infection, 12 that impacted WNV and one additional flavivirus, and 8 factors influencing infection of all three flaviviruses. Among these, we identified two host proteins with roles in antiviral signaling and cell-intrinsic immunity. USP15 is a host deubiquitylase that promotes WNV infection and interacts with flavivirus NS5 proteins. We show USP15 is required for WNV infection and acts as a negative regulator of Type I interferon in this context. We will establish the role of the WNV NS5-USP15 interaction in this phenotype by identifying the residues in USP15 that are critical for interaction with NS5 and generating NS5-binding deficient USP15 mutants to test in our studies. Activation of the Type I interferon response requires ubiquitylation of RIG-I, and we propose that USP15 inhibits Type I interferon signaling via deubiquitylation of RIG-I. To test this, we will monitor activation and ubiquitylation of RIG-I upon knockdown of USP15 and determine the role of the USP15- NS5 interaction in this response. We have also identified the flavivirus capsid-interacting host protein WIBG, which restricts WNV infection. WIBG is involved in RNA regulatory processes, including nonsense-mediated RNA decay (NMD) and interaction with the exon-junction complex (EJC) proteins, Y14 and MAGOH. We show that NMD is inhibited and that the interaction of WIBG with Y14/MAGOH is disrupted in flaviviral infection. Moreover, we demonstrate that NMD and the EJC are antiviral, as depletion of a canonical NMD factor, UPF1, and an EJC protein, MAGOH, results in increased flavivirus infection. We propose that NMD is an antiviral host process that is antagonized by flaviviruses. We will determine the mechanism by which NMD inhibits WNV infection and determine how the WIBG-capsid interaction influences this process. The goal of this proposal is to uncover the mechanisms by which flaviviruses subvert host innate antiviral mechanisms.",,2024,THOMAS JEFFERSON UNIVERSITY,390000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22361,1R01AI155983-01,Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and -experienced Individuals,"Project Title: Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and - experienced Individuals Project Summary Zika virus (ZIKV) is a member of the flavivirus genus that recently precipitated widespread cases of neurological pathology and congenital neurologic defects. In response, a multilateral coalition of investigators designed and developed multiple vaccine candidates that elicited potent ZIKV-neutralizing antibodies, which were shown to correlate with disease protection in animal models. Despite these advances, it remains unclear how the ZIKV immunization antibody response is shaped in humans with and without prior exposure to other flaviviruses, such as dengue virus (DENV), Japanese encephalitis (JEV) or yellow fever virus (YFV); particularly as these viruses all have significant epidemiologic overlap with ZIKV. Our long-term goal is to understand the underlying humoral mechanisms generated by flavivirus vaccination, which can provide long-term protection in flavivirus-naïve and/or -experienced populations. Such information would guide vaccination strategies in flavivirus-endemic areas or among flavivirus-naïve individuals traveling to endemic areas. The overall objective of this proposed research is to evaluate the specificity and function of the B cell repertoire elicited by ZIKV vaccination in flavivirus- naïve and -experienced individuals. To achieve these goals, this research will utilize leading-edge technologies to sequence B cell receptors (BCRs) from flavivirus-specific, single B cells using RNAseq and Next Generation Sequencing (NGS). BCRs will be compared between Zika vaccinated individuals, and to previously published monoclonal antibodies, to determine the prevalence of B cell lineages, gene assignment, degree of somatic hypermutation (SHM), and lengths of heavy chain complementary-determining region 3 (HCDR3). Common B cell lineages will be expressed as monoclonal antibodies and evaluated for their specificity, function, structural, and ability to protect against flavivirus challenges in mouse models. A total of 40 samples will be evaluated from individuals representing 5 groups in 3 different Phase I Zika vaccine clinical trials: a) Flavivirus-naïve individuals who were vaccinated using a Zika purified inactivated whole virus vaccine (ZPIV) b) Flavivirus-naïve individuals who were vaccinated with an adeno-vectored Zika M-E (Ad26.ZIKV.M-Env) c) Individuals living in Puerto Rico with prior dengue infection who were ZPIV vaccinated d) JEV (IXIAROÃ'®) vaccinated individuals who were ZPIV vaccinated and e) YFV (YV-VAXÃ'®) vaccinated individuals who were ZPIV vaccinated. Flavivirus-naïve, Zika vaccinated individuals (Groups a-b) will be explored in Aim 1 and Flavivirus-experienced individuals, either by prior infection (Group c) or by prior vaccination (Groups d-e), will be explored in Aim 2. Aim 3 will examine a late timepoint (6 months) following the last ZPIV vaccination to determine the longevity of the circulating B cell lineages characterized in Aims 1 and 2. Evaluating prevalent B cell lineages responding to Zika vaccination will reveal the specificity, function and durability of the humoral response among individuals living in different regions. These studies will provide insights into the potency and durability of ZIKV vaccine responses in both flavivirus- naïve and -experienced individuals and may translate into vaccine strategies that yield long-lived protection.",,2026,HENRY M. JACKSON FDN FOR THE ADV MIL/MED,864207,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Characterisation of vaccine-induced immunity",2021 +P22362,1R44TR003549-01,Point-of-Care Rapid RNA test for Zika,"Point-of-Care Rapid RNA test for Zika CrossLife Technologies Inc. Project Summary/Abstract We aim to develop a rapid point-of-test that detects ZIKV at the point-of-need in < 30 minutes and is appropriate for non-laboratory settings and non-technical personnel. Our proprietary test exploits a novel probe reaction chemistry that allows multiplexed detection of DNA or RNA without sample purification, making it operable as a simple, hand-held test. Patient samples to be input directly into the device without pre- processing and a disposable cartridge carry out amplification of all targets and reports visible results that can be read by eye. We have demonstrated the feasibility of a novel and simple detection of ZIKV using TARA (Templated Assisted Rapid Assay). The key goals of the Phase 2 project are to 1) develop and evaluate automated paper strip device and to 2) validate it using clinical samples. We will evaluate the automated paper strip device using 200 samples from a Navy-IRB approved protocol through our CRADA collaboration with U.S. Naval Medical Research Center and the U.S. Naval Medical Research Unit SIX. We expect a sensitivity (>90%) and specificity (>90%) to the qRT-PCR data on the same samples. The successful achievement of 1) time to result < 30 min, 2) sensitivity > 90%, specificity > 90% and LOD < 500 copies/test, 3) > 90% user feedback on ease of use need for CLIA waiver, 4) requires no instrumentation, power source, or refrigeration of reagents, and 5) quantitative criteria for measuring the outcome of each task are exceeds or equivalent to the RT-PCR molecular test.",,2023,"CROSSLIFE TECHNOLOGIES, INC.",999916,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P22363,1R01AI153434-01A1,Flavivirus immunity in endemic and non-endemic human cohorts,"PROJECT SUMMARY The global spread of the arthropod borne flaviviruses dengue (DENV1-4) and Zika (ZIKV) viruses are major global public health challenges. World health organizations are calling for scientific communities to respond to this emerging threat with vaccines, therapeutics and diagnostics. However, existing gaps in fundamental knowledge about DENV and ZIKV immunity, specifically how type-specific immunity to each serotype develops and is sustained, makes rational vaccine development particularly difficult. The dominant immunity model comes from human challenge studies on DENV (1910’s-1940’s) and posits that first infection induces neutralizing antibodies that provide life-long sterilizing immunity to repeat infections by the same (homotypic) serotype virus, and this model has been extended to ZIKV without rigorous evaluation. However, recent studies from DENV endemic regions provide evidence of homotypic re-infection and natural immune boosting over time and our preliminary data from a non-endemic, Portland, Oregon resident DENV and ZIKV immune cohort show type- specific Abs decay â€Â"" lose both potency and breadth - over time, calling into question sterilizing immunity and leading us to hypothesize that natural flavivirus (ZIKV and DENV) protective immunity is context dependent: in endemic transmission settings intermittent asymptomatic boosting maintains potency and breadth of virus specific immunity and in non-endemic or very low transmission settings potency and breadth of flavivirus immunity significantly wanes. To test this hypothesis, we propose to prospectively characterize and compare DENV and ZIKV immunity in a regularly re-exposed endemic cohort in Ponce, Puerto Rico with immunity in an un-boosted, non-endemic cohort of DENV immunes in Portland. This is a controversial and novel hypothesis that will call for substantial supporting evidence, hence we will compare and contrast three highly relevant and related markers of boosting between the two cohorts: The potency and breadth of neutralizing serum DENV and ZIKV specific Abs (Aim 1), the frequency of and potency of DENV and ZIKV non-structural protein 1 (NS1) specific antibodies (Aim 2), and the frequency and specificity of DENV and ZIKV specific memory B-cells (MBCs) (Aim 3). We expect to find that Abs and MBCs decline at a significantly greater rate in individuals from the non- endemic setting compared to the endemic setting supporting the hypothesis that boosting plays a critical role in natural immunity for these viruses, with implications for future vaccine development. Because MBCs are functionally linked to Abs, quantifying virus specific MBCs tests a mechanistic connection between repeat infection and Ab titer boosting. Our proposed work will comprehensively assess the role transmission context plays in flavivirus immunity using two highly relevant and mechanistically linked determinants (Ab and MBC). Irrespective of specific results, the knowledge obtained from the proposed work will be essential to DENV vaccine development and mechanistic understanding of flavivirus Ab mediated immunity.",,2026,OREGON HEALTH & SCIENCE UNIVERSITY,395704,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22364,1R01AI153419-01A1,Mechanistic Insights into flavivirus NS5-mediated STAT2 Suppression,"The family of flavivirus consists of over 90 vector-borne, single-stranded RNA-containing viruses, including Dengue virus (DENV) and Zika virus (ZIKV), which cause major epidemics among humans and pose a serious threat to global public health. No vaccines or antivirals exist to prevent or treat infections caused by DENV, ZIKV, and some other flaviviruses. To establish infection, flaviviruses need to overcome the antiviral state induced by type 1 interferon (IFN-1), the first line of host defense. In this regard, flaviviruses have encoded several antagonists to suppress IFN responses. For example, the nonstructural NS5 proteins of DENV, ZIKV, and some other flaviviruses have been shown to be potent suppressor of IFN signaling, targeting different steps of the IFN signaling pathway. Like DENV, ZIKV NS5 protein bind human signal transducer and activator of transcription 2 (hSTAT2) protein and trigger its proteasomal degradation, albeit using different downstream mechanisms. To elucidate the mechanistic basis of flavivirus NS5-mediated hSTAT2 suppression, we propose to provide structural insight into the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 complexes, which, in turn, will guide interrogation of the consequence(s) of the flavivirus NS5-hSTAT2 interactions in proteasome-mediated degradation of hSTAT2 and suppression of IFN signaling. Toward this goal, we will use structural, biochemical, molecular, cellular and virology approaches to investigate the structural basis of the ZIKV NS5-hSTAT2 and DENV NS5-hSTAT2 interactions and their functional consequence. In Aim 1, we will establish the structural basis of the ZIKV-hSTAT2 interaction by using X-ray crystallography and cryo-electron microscopy and validate our observations with mutational and in vitro pull-down analyses. In Aim 2, we will examine the ZIKV NS5-hSTAT2 interaction at a cellular level and investigate the functional consequence of the ZIKV NS5-hSTAT2 interaction through evaluation of the mutational effects of ZIKV NS5 on hSTAT2 degradation, IFN response and viral infection. The results of these studies will provide critical structural and functional insights into the virus- and species-specific ZIKV NS5-hSTAT2 interaction, thereby establishing a mechanistic link between flavivirus NS5 proteins, hSTAT2 degradation, suppression of the IFN response and viral infection. Results from the proposed studies will ultimately benefit development of novel antivirals and live vaccines against flaviviruses infection.",,2026,UNIVERSITY OF CALIFORNIA RIVERSIDE,388750,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22365,1R56DC019113-01A1,Auditory physiology in children exposed to the Zika virus,"Abstract: Prenatal exposure to the mosquito-borne Zika virus (ZIKV) can cause a wide range of neurologic abnormalities and developmental disabilities. Studies in children with microcephaly due to ZIKV have identified language delays, but there is a gap in knowledge regarding the state of the auditory system because most evaluations of auditory function in these populations have been limited to newborn hearing screening and assessment of peripheral hearing sensitivity. Additionally, a large group of children with prenatal exposure to ZIKV but without microcephaly has been largely understudied despite the emerging evidence of residual ZIKV effects on speech/language development in those otherwise asymptomatic cases. Identifying auditory problems that could impact listening and communication is critical for preparing adequate care plans as the children enter school. The proposed international research collaboration will focus on filling in these knowledge gaps by systematically and comprehensively characterizing auditory function and its relationship to communicative developmental outcomes in children 4-8 years of age with history of prenatal exposure to ZIKV. The following groups will be studied: (1) children with ZIKV-related microcephaly; (2) children prenatally exposed to ZIKV without microcephaly; and (3) control subjects matched on age, sex, and socioeconomic status (SES). The proposed longitudinal study will address three specific aims: Specific Aim 1 will characterize auditory function in children with microcephaly due to the ZIKV. We hypothesize that, despite normal peripheral hearing test results, cortical responses will differ from those of age-, sex-, and SES-matched controls. Specific Aim 2 will characterize auditory function in children exposed to the ZIKV but without microcephaly. We hypothesize that this group will have altered auditory function, indexed by atypical cortical responses. Specific Aim 3 will evaluate concurrent and predictive relationships between auditory neural responses and language outcomes in children with prenatal exposure to ZIKV with and without microcephaly. For all participants, we will acquire auditory physiologic responses from the middle ear through cortex and measures of speech/language ability at three time points over 30 months to identify potential indicators related to risk for delays in development of speech, language, and listening problems. We will also examine how additional risk factors, medical history, and general neurodevelopment relate to auditory response findings. The proposed work will be accomplished through a collaboration between scientists at Vanderbilt University Medical Center and researchers in two states in Brazil who follow some of the largest cohorts of ZIKV-exposed infants in the world. Colleagues in the US and Brazil will have complementary roles in providing expertise in characterizing physiologic function and developing clinical applications in this unique and important population. The results of this work will clarify the impact of ZIKV on auditory function and identify clinically useful measures for detection and management of risk for communication delays that are needed to facilitate adaptive functioning and academic success.",,2023,VANDERBILT UNIVERSITY MEDICAL CENTER,523564,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P22366,5R01AI145918-02,Trade-offs between Arbovirus Transmission and Clearance in Native and Novel Hosts,"Research Summary The recent introduction of Zika virus (ZIKV) into the New World sparked concern that the virus would emerge into a sylvatic cycle in American non-human primates (NHPs) and mosquitoes. The ability of a pathogen to emerge into a novel host species is determined, in part, by the virulence of that pathogen in the novel species. Current theory on the evolution of virulence rests on the premise that pathogen fitness is maximized by optimizing the trade-off between instantaneous pathogen transmissibility and duration of infection. While most theoretical studies of virulence evolution have focused on the trade-off between transmission and host mortality, the majority of pathogens do not kill their hosts. Instead, most infections are curtailed by the host immune response, leading to a transmission-clearance trade-off. Studies of the transmission-clearance trade-off are scarce, but we have previously found that, across multiple studies in the literature, there is an inverse relationship between peak virus titer and duration of infection when arthropod-borne viruses are experimentally inoculated into natural hosts. Moreover, we have leveraged these data to model alternate transmission strategies, namely a “tortoise” strategy of low magnitude, long duration viremia and a “hare” strategy of short duration, high magnitude viremia and found that arboviruses that adopted a tortoise strategy had higher rates of persistence in both host and vector populations. Nonetheless current understanding of transmission-clearance trade-offs in arboviruses is rudimentary, and integrated experimental and modeling studies of arbovirus trade-offs in ecologically-relevant host and vector species are needed to appropriately assess the risk of establishment of sylvatic cycles in new areas and the subsequent risk of emergence from such cycles. To this end, we will quantify dynamics of ZIKV and dengue virus (DENV) infection, immune response, and transmission in native NHP hosts (cynomolgus macaques) as well as novel, American NHPs (squirrel monkeys) to identify transmission-clearance trade-offs, and we will build models to predict the impact of such trade-offs on virus persistence in host populations. DENV is chosen as a counterpoint to ZIKV because, despite circulating in humans in the Americas for centuries, it has not yet established an American sylvatic cycle [17]. We will test four specific hypotheses: (i) In native hosts and novel hosts, sylvatic arboviruses experience a transmission-clearance trade-off; (ii) In native and novel hosts, the innate immune response shapes the transmission-clearance trade-off; (iii) Sylvatic arboviruses experience different transmission-clearance trade-offs in native hosts and novel hosts, resulting in less transmission from novel hosts; (iv) DENV and ZIKV lineages from human-endemic transmission cycles experience different transmission-clearance trade-offs than their sylvatic ancestors in native NHP hosts, but similar patterns in novel NHP hosts.",,2024,NEW MEXICO STATE UNIVERSITY LAS CRUCES,733645,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease models | Animal source and routes of transmission",2020 +P22367,5R01AI149502-02,Multiplex Serodiagnostic Assays for Pathogenic Arboviruses in Brazil,"Abstract A critical need exists for highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses in geographic regions, such as Brazil, where multiple flaviviruses including Zika virus (ZIKV), four serotypes of dengue virus (DENV1-4), West Nile virus (WNV), and yellow fever (YFV), as well as chikungunya virus (CHIKV), Mayaro virus (MAYV) (both alphaviruses) and Oropouche virus (OROV) (a bunyavirus), are endemic. However, cross-reactivity of antibodies against different flaviviruses present major challenges, such that even neutralization tests cannot confirm a specific flavivirus infection among individuals who have experienced previous flavivirus infections. The objective of the proposed research is to develop highly sensitive and specific serodiagnostic tests to discriminate infections by pathogenic arboviruses. The central hypothesis is that a combination of fusion loop (FL)-mutated VLPs and nonstructural protein 1 (NS1) proteins of different flaviviruses and recombinant proteins and VLPs of CHIKV, MAYV and OROV in multiplex formats can distinguish different arbovirus infections. The first Aim is to develop and validate multiplex IgG and IgM microsphere immunoassays (MIAs) based on recombinant proteins to distinguish arbovirus infections. We will employ recombinant NS1 proteins of 7 flaviviruses, envelope (E) 2 protein and nucleocapsid (N) protein of CHIKV, MAYV and OROV for multiplex IgG and IgM MIAs using Luminex 200 and test with 15 panels of convalescent-phase serum/plasma from individuals with confirmed arbovirus infections. The second Aim is to develop and validate multiplex IgG and IgM MIAs based on VLPs to distinguish arbovirus infections. We will use purified and FL-mutated VLPs of 7 flaviviruses and VLPs of CHIKV, MAYV and OROV, and test with 15 panels of serum/plasma as in Aim 1. The third Aim is to compare the multiplex IgM MIAs and IgG MIAs with currently available serodiagnostic assays to determine arbovirus seroprevalence in Bahia, a northeastern state with multiple arbovirus transmissions in Brazil. For serodiagnosis, we will test serum samples from patients with acute febrile illness and their follow-up at outpatient clinics of 4 study sites (Salvador, Feira de Santana, Itabuna and Campo Formoso) in Bahia. For seroprevalence study, we will enroll and test household members at communities of the 4 study sites. The proposed study is innovative as it employs two promising antigens (NS1 protein and FL-mutated VLPs) to overcome flavivirus cross-reactivity for seven flaviviruses, as opposed to traditional E protein-based tests, plus CHIKV, MAYV and OROV in two multiplex formats to discriminate arbovirus infections in Brazil. It would contribute to a detailed understanding of the epidemiology of 10 arbovirus infections in Bahia. The successful employment of the multiplex platforms can serve as a new paradigm for serodiagnosis and serosurveillance in countries where multiple arboviruses co-circulate. Most importantly, this research will facilitate the implementation of arbovirus vaccines, in particular ZIKV, DENV and CHIKV vaccines in endemic regions.",,2024,UNIVERSITY OF HAWAII AT MANOA,155959,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +P22368,1R01AI158194-01A1,Structure-based design of broad flavivirus immunogens,"SUMMARY Dengue virus is a mosquito-transmitted flavivirus that causes an estimated 390 million human infections each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions. Primary infection by a single DENV serotype results in febrile illness and subsequent durable immunity to that serotype. Secondary infections by heterotypic serotypes can lead to severe shock syndrome and death. Severe Dengue disease is caused in part by cross-reactive antibodies elicited during primary infection that can bind heterologous DENV serotypes but cannot neutralize them. Instead, these non-neutralizing antibodies facilitate entry and infection in Fcγ receptor-positive cells, thus causing ""antibody-dependent enhancement"" (ADE) of infection. While a live-attenuated four-component chimeric vaccine was recently deployed in 19 countries and Europe, this vaccine does not protect naïve individuals against symptomatic or severe infection, and may even exacerbate disease in some cases. Furthermore, the global emergence of Zika virus (ZIKV), and the potential for ADE between DENV and ZIKV, raises concerns for vaccine strategies containing most or all epitopes in the E glycoprotein. Nonetheless, the isolation and characterization of protective and, in some cases, broadly-neutralizing antibodies indicates that certain epitopes within the E glycoprotein may have the capacity to elicit broadly protective responses. Here, we utilize innovative protein engineering approaches to develop “immune-focused” antigens as potential vaccine candidates, in which epitopes that induce non-neutralizing antibodies are masked by engineered mutations or glycosylation. Our hypothesis is that masking of these unfavorable epitopes will skew the immune response toward a stronger neutralizing, protective, and broad response. Aims 1 and 2 focus on critical epitopes in DENV and ZIKV E domain III (EDIII), and Aim 3 explores glycan masking of the ZIKV E prefusion dimer to immune focus on the E-dimer epitope (EDE). EDIII is attractive for subunit vaccine design because it is the target of potently neutralizing and protective antibodies for both DENV and ZIKV. However, immunization with wild-type EDIII protein results in induction of both neutralizing and non-neutralizing antibodies that engage a variety of epitopes. We have used phage display to mask unproductive epitopes of DENV and ZIKV EDIIIs by mutation, while maintaining neutralizing epitopes. These “resurfaced EDIIIs” (rsDIIIs) will be conjugated to protein nanoparticles and their capacity to induce neutralizing and protective antibody response in mice evaluated. To immune focus the prefusion E dimer on the EDE, we have developed a mammalian display system that allows for rapid evaluation of E dimer constructs for binding to EDE mAbs. We will utilize this system to screen variants with multiple engineered glycosylation sites that mask the surface outside of the EDE. The most promising candidates will be tested for their capacity to induce EDE-like mAbs in mice. This work will provide a proof-of-concept for novel subunit vaccine candidates against DENV, ZIKV, and possibly other flaviviruses of global concern.",,2026,ALBERT EINSTEIN COLLEGE OF MEDICINE,755795,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22369,5R21AI151963-02,Deep mutational scanning of the Zika virus NS5 protein,"Flaviviruses represent serious global health challenges. Research on these viruses, including Zika virus (ZIKV), is crucial to help prevent the spread of epidemics and will ideally result in the availability of therapies. Antiviral development would be aided by a deeper understanding of the mechanisms of viral replication. The flavivirus NS5 protein encodes multiple critical proviral activities. These include the enzymatic methyltransferase and polymerase activities, which are required for viral genome amplification inside infected cells. We have also identified an NS5 activity that is required for the spread of virus between cells, presumably at the level of infectious virus assembly or release. Finally, NS5 is also a major interferon antagonist that permits infection in the face of potential host innate immune responses. Apart from the basic elements of the methyltransferase and polymerase enzymatic activities, such as substrate binding and active site residues, little to nothing is known about the sequence determinants that contribute to this vast array of activities. We hypothesize that ZIKV NS5 encodes numerous overlapping functions that can be genetically separated. To identify these determinants, we will generate libraries comprised of all possible single amino variants in the NS5 protein. To do so, we will use a novel infectious clone of a contemporary ZIKV strain that we generated. We will screen this library for the capacity to undergo RNA replication and spread by infecting cells and looking at which viruses are present after only one day (to allow only replication, not spread, to occur) and several days (which will allow spread of viruses between cells). The mutational tolerance for each activity will be determined by deep sequencing, the viral RNAs in infected cells at the two time points and comparing them to the initial plasmid library. We will also passage this library in cells treated with interferon to select mutants that retain the capacity to inhibit STAT2, a mediator of innate immune response. This activity will be similarly defined by deep sequencing. The sequencing approach will use powerful next-generation sequencing technologies to assay all possible NS5 single amino acid mutations simultaneously and is a highly scalable strategy to study ZIKV evolutionary potential. The results of this project will provide in-depth insights into flavivirus host cell interactions and replication mechanisms that may aid in the development of therapeutic efforts for ZIKV and could perhaps be further applied in combating other future virus outbreaks.",,2022,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,218122,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P22370,5R21AI150671-02,Endogenous ligand of the NK activating receptor NKp46,"Natural killer cells (NK) act as a first line of defense against infection and cancer. NK activation is controlled by a balance of signals transmitted by activating and inhibitory NK receptors. The activating receptor NKp46 is considered the major activating receptor in natural cytotoxicity against autologous, allogeneic, and xenogeneic target cells. NKp46 is conserved in mammals and virtually ubiquitously expressed on NK, suggesting it is functionally important. Mice deficient in Ncr1, the gene encoding NKp46, are impaired in tumor immune surveillance, have more severe influenza A, metapneumovirus, reovirus, and fusobacterium infections, and graft versus host disease. The endogenous ligand of this important activating NK receptor is not known, despite decades of searching. Our preliminary work suggests that NKp46 recognizes calreticulin (CRT), which is normally found inside the endoplasmic reticulum (ER) but gets transferred to the cell surface in ER-stressed cells or tumor cells treated with some cancer drugs. An NKp46-Ig fusion protein specifically pulls down cell-surface CRT (ecto-CRT) and preliminary data using surface plasmon resonance indicate specific binding. Knocking down CALR, the gene encoding for CRT, or adding blocking antibodies to CRT inhibits NKp46-mediated NK killing. Some chemotherapeutic agents and radiotherapy induce an immunostimulatory type of programmed cell death in cancer cells, known as immunogenic cell death (ICD), which removes surviving tumor cells after treatment. The mechanism behind ICD has been linked to ecto-CRT, which serves as an ""eat me""/phagocytic signal for dendritic cells, which then activate anti-tumor CD8+ T cells by cross-priming. Here we hypothesize that NKp46 recognizes ecto-CRT, and that NK recognition of ER-stressed cells via NKp46 interaction with ecto-CRT plays an important role in ICD and NK-mediated immune defense more generally. In preliminary data, infection with ZIKV, which replicates in the ER and causes ER stress, and treatment of tumor cell lines with ICD-inducing chemotherapy drugs induces ecto-CRT and NKp46-dependent NK killing. Moreover, CRT-coated tumor cells become NK cell targets, and NCR1 knockout in an NK cell line strongly inhibits its killing of targets with exposed CRT. To test our hypotheses, we will first confirm that ecto-CRT is a ligand for NKp46 by using biophysical methods to characterize ecto-CRT and NKp46 binding and identifying the regions of CRT responsible for the interaction. Genetic manipulation or blocking of NKp46 on NK and of ecto-CRT on tumor targets will examine the role of this receptor-ligand interaction in NK recognition, immune synapse formation and functional responses to infected and tumor cells. NK killing of untreated tumor cells and tumor cells treated with ICD-inducing and noninducing drugs will be compared. The in vivo role of NKp46 in controlling ZIKV infection and mouse tumors (without and with chemotherapy) will be assessed by comparing viral levels and tumor growth, NK cell infiltration of tumors and survival in wild-type and Ncr1-/- mice. ",,2022,BOSTON CHILDREN'S HOSPITAL,221250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P22371,5K22AI143963-02,Regulation of positive-stranded RNA virus infection by host factors of the endomembrane system,"PROJECT SUMMARY Positive-stranded RNA viruses, including enteroviruses and flaviviruses, are responsible for severe disease manifestations worldwide. Enteroviruses, such as enterovirus 71 (EV71) and coxsackievirus B3 (CVB), enter the host via the fecal-oral route and, therefore, must initially cross the intestinal epithelium to cause severe disease, including acute flaccid paralysis and meningitis. Conversely, flaviviruses enter the host through the bite of an infect arthropod. Zika virus (ZIKV) and dengue virus (DENV) are transmitted by mosquitos in subtropical and tropical regions of the world. Importantly, several flaviviruses are known to cause severe neurological disease, including congenital Zika syndrome, which was first observed during a 2015 Brazilian outbreak. To cause neurological disease, the majority of viruses must cross the blood brain barrier. Thus, an understanding of cellular processes that regulate virus infection of barrier cells can facilitate the development of novel broad-range antiviral strategies and therapeutics. Interestingly, all positive-stranded RNA viruses require the manipulation of host membranes to concentrate viral and host factors at sites of viral replication. During infection enteroviruses and flaviviruses manipulate membranes of the endomembrane system, which connects the nuclear membrane to the extracellular space via vesicle trafficking between the endoplasmic reticulum (ER) and Golgi complex. Thus, I sought to better understand the shared cellular processes associated with the endomembrane system that are manipulated during virus infection. I directly compared ~50 host endomembrane factors for their ability to regulate enterovirus (EV71 and CVB) and flavivirus (ZIKV and DENV) infection. My preliminary results identified members of the reticulophagy regulator (RETREG) protein family and several soluble N-ethylmaleimide-sensitive associated receptor (SNARE) proteins, including vesicle associated membrane protein 7 (VAMP7). Interestingly, these proteins are all associated with autophagy, which is a cellular stress response pathway that is manipulated by enteroviruses and flaviviruses during infection. Thus, I hypothesize that select components of the endomembrane system regulate virus infection through facilitation of autophagic processes. To address the mechanisms of viral manipulation of the endomembrane system, I have developed plasmid-based reporters that will be used to monitor (1) ER and Golgi morphology and (2) induction of autophagy during infection and host factor depletion. These novel reporters will be used for long-term time-lapse imaging in a cellular model of the blood brain barrier. Furthermore, I will provide mechanistic insight into the role of RETREG proteins during enterovirus and flavivirus infection. Additionally, I will characterize enterovirus-induced autophagy using a blood brain barrier cell model and a highly relevant primary human intestinal epithelium model, that we have established in our laboratory. Information derived from our results will provide significant insight into the shared cellular processes manipulated by these viruses to efficiently replicate in cellular barriers.",,2022,UNIVERSITY OF ALABAMA AT BIRMINGHAM,108000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P22372,5U01AI148069-02,Quanitifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases,"Project Summary/Abstract Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes- borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections. Novel vector control approaches and intervention delivery strategies to contain ABVs are urgently needed. Targeted indoor residual spraying (TIRS, applying residual insecticides on Aedes aegypti resting sites such as exposed low walls [<1.5m], under furniture, and on dark surfaces) is a rational vector control approach that exploits Ae. aegypti resting behavior to focalize insecticide applications with no loss in residual efficacy. Recently published systematic reviews have identified TIRS as a very promising approach for ABD prevention, but highlighted the limited evidence-base for this intervention due to the absence of efficacy estimates from randomized controlled trials with epidemiological endpoints performed in endemic settings. In response to such critical need, we will pursue a two-arm, parallel, unblinded cluster randomized trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory- confirmed (virologically or serologically) ABV clinical disease (e.g., dengue, Zika or chikungunya) (primary endpoint). Secondary endpoints will include: a) Laboratory-confirmed (serologically) DENV, CHIKV or ZIKV seroconversion in children aged 2-15 at enrollment; b) Ae. aegypti mosquito infection rates with DENV, CHIKV or ZIKV; c) Ae. aegypti indoor entomological indices. The trial will be conducted in the city of Merida (Yucatan State, Mexico, population ~1million), where we will prospectively follow a population of 4,600 children 2-15 years at enrollment, distributed in 50 clusters of 5x5 city blocks each (~92 children per cluster), randomly allocated to receive either TIRS treatment (n=25) or not (n=25). Trained personnel from the Federal Ministry of Health will perform TIRS in all houses from the treatment clusters ~1-2 months prior to the beginning of the peak ABV transmission season. Active monitoring for symptomatic ABD infections will be performed by field nurses and doctors through weekly household visits and enhanced surveillance (phone calls, monitoring of suspected cases to Merida’s hospital/clinic system), whereas annual sero-surveys will be performed after each transmission season. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to guide insecticide applications; change to preemptive control (pre- ABV transmission season rather than in response to symptomatic cases); the use of insecticide formulations to which Ae. Aegypti is susceptible.",,2025,EMORY UNIVERSITY,1322878,Human Populations | Disease Vectors,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,"Vector control strategies | Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures",2020 +P22373,1K22AI144050-01,Characterization of a human-specific positive regulator of flavivirus infection,"Project Summary/Abstract Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV) or Dengue virus (DENV) are cause of great health and economic concerns worldwide. YFV is the prototypical member of the flavivirus genus, and one of the first human pathogenic viruses that has been identified. Despite the development of a very potent vaccine in the 1930’s, YFV still represents a real theat. Recent outbreaks in Angola and Brazil, over the past two years, occurred in areas with low vaccination coverage. These resurgence events have exemplified the threat and have highlighted the need for the protection of an estimated 400 to 500 million people worldwide. Facing a significant vaccine shortage, fractional doses of vaccine are now used during vaccination campaigns despite no/limited evidence of long-term protection, hence underscoring the urgent necessity of developing novel strategies to clinically manage future YFV outbreaks. Our knowledge of the YFV infectious cycle in vitro and in vivo is extremely limited which has ultimately hampered the development of specific therapies to treat YFV infection, as none is currently available. I recently identified a novel host regulator of YFV infection in human cells that is required for effective YFV infection and replication in vitro. As it is not expressed in mice, this factor could also contribute to the human/primate-specific tropism of YFV. Building on a robust set of preliminary data, I hypothesize that this factor regulates RNA replication or protein translation through direct binding to viral elements. In Aim 1, I will explore the mechanisms by which this factor regulates the replication of the YFV vaccine strain YFV-17D in vitro as well as the host and virus determinants that govern such regulation. In Aim 2, I will determine the role of this factor on the replication of a virulent YFV strain, YFV-Asibi, as well as of other flaviviruses of interest such as ZIKV and DENV. I will also seek to explore the role of this factor using more relevant cell culture system such as primary human hepatocytes by using specific inhibitor of this factor. In Aim 3, I will use a humanized mouse model I recently developed and that is permissive to YFV infection to evaluate the role of this factor on YFV-Asibi and YFV-17D replication in vivo, by treating mice with specific inhibitor of the identified host factor. Altogether, my strong expertise in studying YFV virus in vitro and in vivo, combined with the different viral tracking tools and in vivo models I have previously developed, position me very well to conduct the proposed research. This research could provide novel avenues for the specific treatment of YFV infection and enhance our understanding of the host-pathogen interactions that define flavivirus pathogenicity. This K22 Career Transition Award will help me achieve my scientific and career goals, which consist of transitioning toward an independent assistant professor position and establishing an independent NIH-funded research program aiming at elucidating the mechanisms of flavivirus pathogenicity.",,2023,BOSTON UNIVERSITY MEDICAL CAMPUS,162000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22374,1R21AI164049-01,Eliciting and isolating neutralizing antibodies against Powassan virus,"SUMMARY Powassan virus (POWV) is a tick-disseminated flavivirus that causes severe encephalitis, meningitis, and long-term neurological damage. Although POWV infections are relatively rare, the virus is widely distributed among common vectors such as Ixodes scapularis (the deer tick) and the number of reported cases in the US is rising each year. There are no approved vaccines or treatments for POWV infection. The goals of this R21 proposal are two-fold. In Aim 1, we will investigate the potential of protein nanoparticle immunogens bearing recombinantly-expressed POWV glycoprotein E domain III (EDIII) to induce neutralizing antibody response in mice. EDIII is an attractive target for flavivirus subunit vaccine design because it is relatively small (~80 residues) and contains epitopes of protective antibodies against multiple flaviviruses such as Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and Looping Ill virus (LIV). However, EDIII as a monomer is poorly immunogenic because it lacks the capacity to crosslink surface B-cell receptors (BCRs) to stimulate a robust antibody response. This limitation can be overcome by presenting EDIII in multivalent format as part of a protein nanoparticle. We have generated a prototypic POWV EDIII nanoparticle vaccine using Spycatcher/Spytag conjugation technology, and pilot studies have demonstrated this nanoparticle can elicit neutralizing antibodies in mice. We will further optimize this and related POWV nanoparticle vaccines. In Aim 2, we will isolate a large panel of human monoclonal antibodies (hu-mAbs) from a living survivor of POWV infection by single B cell sorting. Hu-mAbs have strong potential as immunotherapies because they are highly specific and their human scaffold minimizes the risk for anti-drug antibody responses. Furthermore, profiling hu-mAbs provides direct information about human immune response that can then be used to inform vaccine design. We will test the POWV hu-mAbs for their capacity to bind POWV E and neutralize POWV reporter virus particles (RVPs). This work will provide new insights and candidates for prevention and treatment of POWV infection.",,2023,ALBERT EINSTEIN COLLEGE OF MEDICINE,252000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +P22375,3R01AI143265-02S1,JAK-STAT Control of Zika Virus-Induced Fetal Injury,"Project Summary The current project, ""Jak STAT control of Zika virus-induced fetal injury"" (R01 AI143265), includes the processing of many nonhuman primate (NHP) and human tissue and cell samples for high throughput RNA sequencing (RNAseq) analysis. Our sample-processing pipeline for these assays includes RNA isolation and quality control (QC), and library construction and library QC. We currently utilize a Biomek FX automated workstation to perform the majority of these work steps in handling high volume samples in our high throughput workload for these analyses. The Biomek FX is 10 years old. Due to the age, it is not reliable, the ability to obtain a future service contract is not guaranteed, and the current configuration and software are not compatible with off- the-shelf protocols. Thus, we are in need of funds to replace this instrument. The purchase of a Biomek i7 Hybrid automated workstation to replace our Biomek FX workstation, allows us to achieve our stated project goals. 0",,2021,UNIVERSITY OF WASHINGTON,328382,Animals | Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P22376,1R21AI156731-01A1,Mechanism of membrane inactivation method to prepare enveloped virus vaccines,"Project Summary / Abstract The World Health Organization’s list of priority pathogens that pose the highest public health risks, and for which there are insufficient treatments, is composed solely of enveloped viruses. Examples of enveloped viruses highly relevant to human health are: HIV, influenza A viruses (IAV), EboV, MERS-CoV, SARS, SARS-CoV-2, CHIKV, NiV, HeV, RSV, ZIKV, and the influenza A (IAV) and B (IBV) viruses. The human cost of their illnesses is in the millions, and the economic cost is in the hundreds of billions of dollars per year. The standard methods for generating vaccines, including whole inactivated virus (WIV), live attenuated virus (LAV), sub-unit, and DNA/RNA, often fail to result in effective prophylaxis. WIV vaccines have some advantages such as their safety and their presentation of multiple antigens to the immune system. However, WIVs often induce insufficient immunity or even vaccine-enhanced disease due to antigen conformational differences between the WIV vaccine and the challenge virus. Our proposal addresses the pressing need for more effective and broadly applicable WIV vaccines by exploring a promising new technology using the antiviral XM-01 (patent applications pending). Current virus inactivation methods for WIV preparation use chemical or physical means that often damage or modify viral antigens, including the glycoproteins, which are important immunogens for the enveloped viruses. This often leads to non-protective or even destructive immune responses. For example, the efficacies of the currently used WIV vaccines for IAV are between 10%-60%. We recently developed a novel vaccine platform that uses XM-01 to target the viral membrane while largely preserving the native conformation of viral glycoproteins. Preliminary data using IAV as a model indicates that immunization with XM-01-inactivated IAV particles improved induction of neutralizing antibodies to both hemagglutinin (HA) and neuraminidase (NA), as well as animal survival, compared to the traditional formalin-inactivated IAV particles. As XM-01 is a broad- spectrum inhibitor of enveloped viruses, our central hypothesis is that virus inactivation with XM-01 improves WIV vaccine development by preserving glycoprotein conformations, facilitating the effective generation of a protective immune response. We will test our hypothesis with two Specific Aims: Aim 1: Determine the mechanism by which XM-01 inactivated virus affords improved immune responses as compared to traditional WIV vaccine methods, using the influenza virus model. Aim 2: Determine XM-01 vaccination safety, efficacy, and breadth of immune responses. We expect this work will improve our understanding of the mechanism by which XM-01 membrane-mediated viral inactivation generates an enhanced protective immune response, and to assess the new method’s safety, efficacy, and ability to generate broadly protective antibodies against heterologous viral strains, overall assessing whether this new mode of inactivation may be amenable for broad improvement of WIV vaccines.",,2023,CORNELL UNIVERSITY,248896,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Bunyaviridae | Coronavirus | Filoviridae | Flaviviridae | Paramyxovirdiae | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P22377,3R01NS120895-01S1,Juan Angel_Diversity Supplement: R01 NS120895,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",51983,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22378,1F31MD015674-01A1,"Characterization of socioeconomic and land use factors related to Aedes aegypti distribution in Maricopa County, Arizona","Project Summary Aedes aegypti mosquitoes are primary vectors of dengue, yellow fever, and the newly emerged threats of Zika and chikungunya viruses. In recent years, mosquito-borne diseases have reemerged as a pressing public health issue around the world, as the geographic range of mosquitoes has increased rapidly due to expanded global trade and travel and potentially due to increased temperatures caused by climate change. Maricopa County, Arizona is potentially at risk for developing Ae. aegypti transmitted diseases due to the established presence of the mosquito vector and the high volume of travelers coming to Arizona from areas with endemic Ae. aegypti- borne disease. In fact, on average, over 25 million travelers cross the border from Mexico (an area with diseases transmitted by the vector) into Arizona each year. Although much research exists on the wide-scale distribution of mosquito vectors, there is less understanding of the local factors that promote mosquito populations or the geographic range of the mosquitoes, especially in a desert climate. It is not known whether there are local socioeconomic or environmental characteristics that support larger Ae. aegypti populations or how mosquitoes move between local populations. We will use a combination of statistical analysis, spatial analysis, and phylogenomic analysis to develop a better understanding of the local factors that support mosquito populations and how mosquito populations are moving over time and space. The long-term goal of this project is to identify small-scale socioeconomic or landscape characteristics that consistently support Ae. aegypti populations and implement interventions with the Vector Control Division in Maricopa County, AZ to reduce mosquito populations, thereby reducing disease transmission risk. The rationale for this application is that the understanding of the distribution, range, and movement of the mosquito populations is a critical component of implementing effective public health efforts that can reduce disease burden and cost by aiming to prevent potential outbreaks of mosquito-borne disease. Hypothesis: Ae. aegypti will not be uniformly distributed throughout Maricopa County, with some areas having larger populations due to differences in infrastructure or landscape characteristics (which are related to neighborhood socioeconomic status) and therefore potential mosquito habitat. Furthermore, we hypothesize that genetically distinct populations will be separated by short distances and will be unique to specific neighborhoods. Aim 1: Characterize the neighborhood socioeconomic factors associated with Ae. aegypti abundance. Aim 2: Characterize landscape traits, such as greenness, that are associated with Ae. aegypti populations. Aim 3: Characterize the origin of and migration between local Ae. aegypti mosquito populations within Maricopa County, Arizona.",,2023,NORTHERN ARIZONA UNIVERSITY,33922,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P22379,1R35NS122310-01,Research Program Award (R35 Clinical Trial Optional) - Dr. Robyn Klein NINDS,"PROJECT SUMMARY/ABSTRACT Viral infections are now recognized as risk factors for diseases of progressive pathological forgetting, supporting a new paradigm in neuroimmunology whereby innate immune molecules that function as modulators of a variety of normal CNS functions induce neurodegenerative diseases during host-pathogen responses. Studying virus-mediated cognitive dysfunction through the multidisciplinary prism of immunology, neuroscience, and virology is critical for the identification of novel mechanisms of disease, discovery of neuroimaging tools and therapeutic treatments for a wide range of diseases of memory disorder. In my laboratory we made unanticipated, paradigm-shifting discoveries of the roles of CNS infiltrating mononuclear cells in microglial-mediated synapse elimination, disrupted adult neurogenesis, and generation of neurotoxic astrocytes using novel models of recovery from encephalitogenic flaviviruses, West Nile (WNV) and Zika (ZIKV) viruses. We identified classical complement proteins and cytokine receptor signaling as novel molecular mediators that regulate synapse elimination, neural stem cell (NSC) fates, neuron-microglia and microglia- astrocyte crosstalk within cortical structures that regulate memory formation and maintenance. We have also begun leveraging novel neuroimaging modalities to develop biomarkers that may be used to predict and monitor patients at risk for memory disorders. Our aim is to understand the mechanisms that induce alterations in synaptic connections and methods of repair that contribute to disruption of neuronal networks after recovery from viral infections. Our research program focuses on three broad areas related to the roles and regulation of innate immune molecules involved in spatial learning using novel murine models of post-infectious cognitive dysfunction. First, using genetic, pharmacologic and PET-MRI, we will identify and define molecular interactions between T cells and microglia or neurons that drive the generation and maintenance of resident memory T cells that promote cognitive dysfunction. We will use scRNAseq under BSL3 conditions to screen for genes and pathways to be targeted via cell-specific deletion of cytokine or chemokine receptors, or administration of agents that inhibit or enhance pathways. We will also develop diagnostic tools that employ ABSL3 PET-MRI. Second, we will define how microglia-astrocyte-NSC interactions in the context of recovery from CNS viral infections limit repair and recovery. We will use global and conditional gene targeting in mice to delineate the in vivo roles of cytokines in neural cell types that regulate astrocyte inflammasome activation and its relationship to neuronal and synapse recovery. We will also define innate immune mechanisms that direct and maintain astrogenosis during acute viral infection and recovery using PET-MRI detection of P2X7R, a marker of reactive astrocytes. Finally, will utilize reporter mice/fate mapping, bone marrow chimeras and scRNAseq to delineate the cytokine-mediated roles of myeloid cells in the generation of neurotoxic astrocytes during WNND recovery. Third, we will examine innate immune mechanisms triggered after viral infections that negatively impact cortical connectivity and determine whether neuroimaging can be used to predict and follow this process. Specifically, we will combine genetic approaches with functional optical intrinsic signal imaging of hemoglobin and calcium dynamics to define mechanisms that negatively impact cortical connectivity. Our research program will define new concepts in the molecular neuroimmunological regulation of synapses, T cell and glial interactions, inform studies of related processes throughout the nervous systems, and will likely enhance our understanding of neurodegenerative and other disorders of memory.",,2029,WASHINGTON UNIVERSITY,868760,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22380,5R21AI148949-02,Mechanisms and Modifiers of Zika Virus Innate Immune Evasion,"Summary Zika virus is a flavivirus that was first isolated in Uganda in 1947, and gained international notoriety during the 2015-2016 epidemic that spread to South America, North America, Pacific islands, and beyond (1-3). Previously associated with a mild or asymptomatic infection transmitted by Aedes mosquitos, the American Zika virus outbreak was associated with a greater incidence of microcephaly and Guillain Barré syndrome in the children of women infected during pregnancy. Evidence for both sexual and asexual transmission of Zika virus coupled with long latency periods continue to fuel public safety concerns. While experimental vaccination strategies are being pursued, there are no known cures for Zika virus infection or specific prophylactic treatments available for high risk professionals or individuals traveling to afflicted regions. Recent studies of molecular pathogenesis and virulence factors used by Zika virus and other flaviviruses have uncovered a general ability to disrupt or evade innate antiviral immune responses, primarily those mediated by type I and type III interferon (IFN), making the viruses more resistant to exogenous IFN therapy and contributing to virulence, tissue penetration, and host tropism. The flavivirus NS5 protein has been recognized as a primary antagonist of IFN-JAK-STAT signaling, and both Dengue virus and Zika virus have been shown to use NS5 to engage and destroy STAT2, an essential transcription regulator in the IFN response. While Dengue virus uses a specific cellular ubiquitin ligase enzyme to target STAT2, Zika virus uses a distinct mechanism mediated by unknown cellular machinery (13). Preliminary studies of Zika-mediated STAT2 degradation and IFN evasion in human cells provided a foundation for the design of sensitive living cell-based assay systems to identify cellular components used for STAT2 degradation and Zika virus replication. As mechanisms of virus host evasion are hypothesized to be high potential targets for therapeutic intervention, two complementary aims are proposed to (Aim 1) identify the cellular components required Zika NS5-mediated STAT2 degradation and (Aim 2) exploit this pathway as a target for small molecule inhibition of Zika replication. Focusing initial hits from these innovative experiments with general and mechanistic counter-screening and low-throughput follow-up analysis will reveal missing mechanistic machinery needed for Zika virus-mediated IFN evasion, provide cellular targets for investigations of virulence and pathogenesis to inform therapeutic interventions, and identify new leads for Zika virus antiviral compounds.",,2023,NORTHWESTERN UNIVERSITY,194148,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2020 +P22381,5R21EB029682-02,Novel 3D printed microneedle patches for detection of viral infections,"Early diagnosis is important for effective disease management. Zika and other flaviviruses cause severe human disease worldwide. Diagnosis and surveillance of the infections are commonly performed by serological assays involving invasive blood sampling techniques, which can cause adverse effects for patients. Skin interstitial fluid (ISF) shares 85% of the proteins in blood, and development of novel, more efficient and less-invasive technologies, for the collection of ISF can significantly facilitate point-of-care diagnosis of viral infections. Microneedle (MN) patches are devices comprised of microprojection arrays that penetrate the outer skin layers to interface directly with intradermal fluid. MNs have been explored for easy, pain-free administration of therapeutic agents, and can be designed to sample ISF from skin in a simple, minimally invasive manner. A novel 3D manufacturing platform termed CLIP (Continuous Liquid Interface Production), affords unparalleled speed and ease of fabricating MNs, which enables unprecedented precision in size, shape, and density of MNs. Utilizing this platform, we have manufactured MNs measuring 250 Ã'µm to above 1000 Ã'µm, comprised of biomedical materials prevalent in FDA approved medical devices. We hypothesize that CLIP 3D printed polymeric MN patches can be used for rapid, painless, and self-applicable collection of ISF for diagnostic purpose. Our objectives are to design and optimize CLIP 3D printed MN patches for rapid and efficient collection of skin ISF (Aim 1), and establish methods for rapid in situ retrieval and assessment of multiple Zika antigens and antibodies using a single MN patch (Aim 2). Completion of this project will establish a new approach to enable quick and self-applicable local skin sampling point-of-care suitable device for the detection of not only viral infections, but also other disease markers. The proposed technology will also provide a practical method for broader population-level surveillance and epidemiological study of Zika infection.",,2023,UNIV OF NORTH CAROLINA CHAPEL HILL,194375,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P22382,3DP1DA051144-02S1,A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups,"ABSTRACT Substantial evidence now indicates that HIV-infected individuals are at a significantly elevated risk for severe COVID-19 disease when infected with SARS-CoV-2. Moreover, persons who use and inject drugs (PWUD and PWID) have a high-risk of HIV infection and exposure to SARS-CoV-2 and face major barriers to accessing antiviral therapies (i.e., are often immunocompromised). The problem is further exacerbated by the emergence of SARS-CoV-2 variants that escape vaccine-mediated immunityâ€Â""it is now evident that immunocompromised individuals promote the evolution of SARS-CoV-2 escape variants and HIV-infected PWUD/PWID with barriers to treatment represent such a population. Consequently, there is a critical unmet medical need for new therapeutics that could treat HIV as well as SARS-CoV-2â€Â""particularly the emerging variants of concern’â€Â""and could be effectively deployed in difficult-to-reach, high-risk populations (e.g., PWUD/PWID). The long-term goal of this work is to develop single-administration therapies for HIV-1 and SARS-CoV-2 variants to effectively reach PWID/PWUD populations. The specific objective of this supplement proposal is to test efficacy of our recently developed Gene Drive Therapies (GDT) against HIV and SARS-CoV-2 variants in patient cells from HIV+ PWID. This effort will build heavily off our recent success in engineering GDTs for HIV-1 (see Parent Award) and Zika Virus (ZIKV), as well as our extensive preliminary in vitro data showing efficacy of GDTs against SARS-CoV-2 variants. The central hypothesisâ€Â""based on our extensive preliminary in vitro studiesâ€Â""is that our engineered GDT candidates will have the capacity to reduce both SARS-CoV-2 viral load and pathogenesis, including of SARS-CoV-2 variants of concern, and HIV viral load, thereby serving as a single-administration, combination therapeutic for HIV-1 and SARS-CoV-2. The rationale for a GDT for SARS-CoV-2 is based on our preliminary data showing that GDTs significantly reduce SARS-CoV-2 replication in cell culture, are equally effective against CoV-2 variants and from extensive studies on HIV-1 in humanized mice and positive FDA meetings. We will achieve our objectives via two specific aims: (i) Quantify in vivo efficacy of the recently developed GDT in reducing SARS-CoV-2 viral replication and pathogenesis in hamsters; and (ii) Develop a lung-organoid co- culture to test efficacy of GDTs against HIV-1 and SARS-CoV-2 in patient-derived cells from HIV+ PWIDs. While the GDT approach carries inherent risks, single-administration therapeutics active against both SARS-CoV-2 variants and HIV would be highly beneficial, particularly for treating difficult-to-reach, high-risk PWID populations. The studies proposed here will also have broad fundamental significance by establishing a novel culture model and tool to assay how SARS-CoV-2 and HIV infections interact in the PWUD/PWID setting (i.e., in the context of Substance Use Disorders (SUDs) in at-risk populations) and will provide in vivo validation of a novel medical countermeasure with therapeutic efficacy against emerging SARS-CoV-2 variants.",,2025,J. DAVID GLADSTONE INSTITUTES,189000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +P22385,1R01AI156187-01A1,Probing Functional States and Inhibition of Flaviviral Proteases Using Nanopore Tweezers,"Project Summary Flavivirus are major mosquito-borne pathogens infecting millions of people worldwide each year. Currently there is no antiviral therapy available for treating West Nile, Dengue and Zika viral infections. The first vaccine CYD- TDV (Dengvaxia) against DENV was approved last year but shows only 56% overall efficacy against the four dengue serotypes. The flaviviral two-component NS2B/NS3 protease is required for viral replication and thus an attractive antiviral target. However, extensive screening and rational design efforts have failed to identify any clinically viable inhibitors at this point. Two key factors have likely contributed to the challenge. First, traditional screening efforts rely primarily on binding affinity to predict the drug efficacy. Yet, increasing evidence has emerged to show that the residence time of drug-target interaction is a more reliable predictor of in vivo pharmacological activity. These kinetic rate parameters are generally not available during early stages of drug discovery. Second, NS2B/NS3 proteases display complex conformational dynamics during function and inhibition, which is still poorly understood. This project aims to develop a new label-free single molecular approach to resolve the conformational states of NS2B/NS3 proteases. Key to the approach is the use of an innovative nanopore tweezers where the protease is confined with the pore lumen, allowing dynamic structural changes during substrate or inhibitor binding to be continuously monitored by current fluctuation signals. Analysis of the current traces will provide a complete profile of binding affinity and kinetic rates as well as the distribution of conformational states. Specifically, we will first build a nanopore tweezers tool set that is readily tunable for trapping various flaviviral proteases. Secondly, we will track and analyze the functional states of the NS2B/NS3 protease in the presence of various substrates. Influence of critical residues, substrate, construct design on the dynamic equilibrium between the “open” and “closed” states will be assessed to provide insight into the mechanism of protease activity. Finally, the nanopore tweezers will be deployed to determine the structural dynamics and binding thermodynamics and kinetics profiles of NS2B/NS3 interacting with various inhibitors. Once the inhibition profiles are established, the nanopore tweezers confined NS2B/NS3 system will be tested for screening a diverse compound library to identity novel allosteric inhibitors with improved drug-like properties compared to active-site inhibitors. This work will provide unprecedented kinetic information on the function- structural dynamics relationship of NS2B/NS3 complex and mechanisms of substrate binding and inhibition, as well as establish a new paradigm for high-throughput drug screening that is independent of enzymatic activity.",,2026,UNIVERSITY OF MASSACHUSETTS AMHERST,425112,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +P22386,1R01NS120895-01,Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis,"Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.",,2026,"RUTGERS, THE STATE UNIV OF N.J.",381727,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22387,5F32HD103313-02,Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection,"PROJECT SUMMARY The Brazilian Zika virus outbreak of 2016 initiated an international public health crisis when it became clear that babies infected in utero were being born with devastating neurological defects. In addition, troubling reports have shown that many infected babies present as “neurologically-normal” at birth but experience later atypical developmental and neurosensory alterations into infancy. The long-term developmental consequences of Zika infection are currently unknown, but mechanisms of its pathobiology have been linked to the preferential injury of axons and myelin. Disrupted or delayed myelination in early life has been previously associated to significant and permanent impairments across domains of sensory, motor, and cognitive abilities. To investigate the impact of fetal Zika infection on postnatal brain development, this study will acquire quantitative magnetic resonance imaging metrics of myelin and axon maturation in an established nonhuman primate model at 6, 12, 24, and 30 months of age (equivalent up to ~ age 10 in humans). This proposed work, therefore, takes a novel approach by tracking whole brain changes in tissue microstructure, in vivo, in an accelerated model of brain development and links those changes to cellular anatomy, post mortem. Behavioral outcomes related to axon and myelin injury will also be investigated. The aims of this proposal have been designed for direct translation to human studies and will establish a valuable resource for predicting and interpreting outcomes of fetal Zika infection.",,2023,NEW YORK UNIVERSITY SCHOOL OF MEDICINE,68110,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2020 +P22388,1K08AI156126-01,Defining mechanisms of Zika-virus associated microcephaly: cell population dynamics and gene expression in infected human cerebral organoids and neural progenitor cells,"PROJECT SUMMARY/ABSTRACT Zika virus swept across the Americas in 2015-16, and it was during this epidemic that the teratogenic consequences of congenital Zika infection were first described. Despite extensive research, it remains unknown how Zika infection causes microcephaly, or whether this pathology is unique to recent strains, Two new tools will facilitate discovery in this area. First, we and others have shown that the human stem cell derived cerebral organoid is a tractable neurodevelopmental model in which to study Zika infection. Second, we have demonstrated that single cell sequencing techniques that enrich for poly-adenylated mRNAs can identify flavivirus-infected cells â€Â"" an unexpected result given flavivirus genomes do not have poly(A) tails. The goal of this study is to determine the mechanisms by which Zika virus disrupts fetal brain development, building on these technical advances. We will employ single cell RNA-sequencing to identify and compare cellular populations in organoids over time, in the presence and absence of Zika virus. This will allow us to distinguish pathogenic disruptions in a) stem cell abundance, b) cell division, and c) differentiation. We will use single cell RNA-sequencing and ribosome profiling to define gene expression responses to Zika infection in neural progenitor cells, thought to be the target of Zika virus in the fetal brain. By comparing viruses of varying pathogenicity in these studies, we will identify differences in host gene expression and viral replication associated with disease severity. The proposed study will address a major unresolved problem in the field of Zika virus pathogenesis, contribute broadly to our understanding of cerebral development, and mature cutting edge technologies for the investigation of questions at the interface of infection and development. The project will be developed under the mentorship of Dr. Lee Gehrke, a leader and expert in the field of RNA virology with a background in developmental biology. Additional scientific and career guidance will be provided by a scientific advisory committee composed of experts in virology, single-cell sequencing, stem-cell derived tissue models, and pediatric infectious disease pathogenesis. The training program will include coursework in computational biology, training in molecular and tissue culture techniques, workshops in leadership, and didactic learning from local seminars as well as national and international conferences. Research and training will occur at the MIT Institute for Medical Engineering and Science, and at Boston Children’s Hospital at the Harvard Medical School. Together, MIT and Harvard Medical School afford extensive resources and expertise in all aspects of the proposed research. Boston Children’s Hospital is a supportive environment committed to providing 85% protected time for this research, and offers workshops in career development and leadership to prepare early-stage investigators for independence. The project will build on the candidate’s background in virology and high-throughput sequencing, allow her to mature as a physician-scientist, and position her to achieve her goal of an independent research career in pediatric infectious disease pathogenesis.",,2026,BOSTON CHILDREN'S HOSPITAL,194940,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P22389,5R43AI145617-02,Discovery and Development of Broad-spectrum Protease Inhibitors of Flaviviruses of Significant Public Health Threats,"Project Summary Mosquito-borne members of the Flavivirus family including Zika virus (ZKV), Dengue virus (DNV) and West Nile virus (WNV), are classified as re-emerging pathogens due to the frequency and severity of recent epidemics. Also known as arboviruses, these viruses are the etiologic agents of many debilitating diseases affecting the human population worldwide. Consequently, vector borne diseases now account for 17% of all infections worldwide. DNV is the fastest growing arboviral disease currently affecting 400 million annually with 96 million cases manifesting into clinical severity and 22,000 deaths, mainly children. WNV is considered the most important causative agent of viral encephalitis worldwide. The recent ZKV infection outbreak has been associated with congenital microcephaly and intracranial calcification and, in adults, with GBS and severe thrombocytopenia. Currently there is no effective treatment for infections caused by these viruses, which highlights the urgent need to find preventive and therapeutic interventions. The Flaviviridae genome is translated into a single polyprotein which is processed to yield 3 structural and 7 nonstructural proteins. The correct processing of the polyprotein is essential for replication of all flaviviruses, which requires both host proteases and the highly conserved viral NS2B-NS3 protease (NS2B-NS3pro). Hence, the viral protease is a rational target for development of small molecule inhibitors that block flavivirus replication. Small molecule antivirals targeting HIV-1-encoded and HCV-encoded proteases have been successfully developed, which supports the concept of developing chemotherapeutic agents targeting the flavivirus NS2B-NS3pro. The innovation of our proposal is: (i) optimization of a highly-sensitive screening assay for the identification of low binding fragment hits; (ii) evolution of fragment and compound hits into broad-spectrum leads; (iii) the use of replicon and plaque assays to test for cellular efficacy and guide optimization. Our preliminary results and the use of multiple cell-based models supports the feasibility of the discovery of broad-spectrum anti-flaviviral therapeutics. The specific aims are: Aim 1: Complete the screening of fragment and compound libraries for the identification of broad-spectrum NS2B-NS3pro hits. Milestone 1: Identify 6-8 structurally distinct broad-spectrum NS2B-NS3pro hits with an IC50 ≤ 25μM. Aim 2a: Iterative 3D-structure and SAR-based discovery of three non-overlapping broad-spectrum NS2B-NS3pro inhibitor series, using a combination of: (i) commercial analogues and (ii) med-chem design and synthesis approach. Milestone 2: Identify three non-overlapping broad-spectrum NS2B- NS3pro inhibitor series with an IC50 ≤ 200nM. Aim 2b: Characterize biochemically potent inhibitors for: (a) mode of inhibition and (b) enzyme:ligand interactions and prioritize compounds with IC50 ≤ 200nM, for cellular efficacy studies. Aim 3a: In vitro evaluation and optimization of biochemically potent compounds for cellular efficacy (EC50) and cytotoxicity (CC50). Milestone 3: Identify 4-6 lead compounds from each series with EC50 ≤ 5μM and CC50 ≥ 200μM. Aim 3b: Conduct in vitro ADME-based lead optimization of compounds with broad spectrum in vitro activity and acceptable therapeutic indices. Phase I Milestone: Identify 2-4 lead compounds exhibiting high bioavailability, weak inhibitor of CYPP450s, optimum stability and are not hERG channel blockers.",,2023,"PLEX PHARMACEUTICALS, INC.",300000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22390,1R21AI166878-01,Haploid-resolved genome assemblies for the arboviral vectors Aedes aegypti and Aedes mascarensis,"Haploid-resolved genome assemblies for the arboviral vectors Aedes aegypti and Aedes mascarensis Project Summary/Abstract Aedes aegypti transmits several arboviral diseases including dengue and Zika fever, which threaten half of the human population worldwide. In this study, we will take advantage of Oxford Nanopore Technology (ONT) sequencing, the TrioCanu binning approach, and Hi-C scaffolding to create haploid-resolved chromosome- level genome assemblies for Ae. aegypti and Ae. mascarensis. These two closely related species show reproductive isolation by hybrid breakdown via formation of intersexes in backcross hybrids. The long-term objective of this research is to decipher the genetic mechanisms of reproductive isolation between Ae. aegypti and closely related species and to translate such fundamental knowledge into safe and efficient methods to control mosquito-borne infectious diseases. Understanding the permeability of species boundaries is increasingly urgent because of recent developments in transgenic- and gene drive-based applications to control disease vectors. The major goal of this proposed R21 project is to develop and validate phased or haplotype-resolved genome assemblies for Ae. aegypti and Ae. mascarensis and use them for identification and characterization of the genomic regions associated with intersex phenotypes in backcross hybrids between the two species. This timely project will meet the demand for new, highly-finished genome references for arboviral vectors based on appropriate innovative tools and the PI’s and Co-I’s expertise. Toward this goal, we propose the following three Specific Aims: (1) Obtain contiguous haploid genome assemblies for the Ae. aegypti RED strain and Ae. mascarensis by integrating ONT, Illumina sequencing, trio binning, and chromosome-scale Hi-C scaffolding; (2) Validate the obtained assemblies and construct high-resolution physical genome maps for Ae. aegypti and Ae. mascarensis using fluorescence in situ hybridization (FISH); and (3) Identify genomic regions in chromosome 1 that are associated with intersex phenotypes. The new, haploid-resolved chromosome-level genome assemblies for Ae. aegypti and Ae. mascarensis will be available to the scientific community through VEuPathDB and NCBI. Identification of the recombination breakpoints and characterization of genomic regions associated with intersex phenotypes will improve our understanding of the mechanisms that maintain species boundaries and determine sex in mosquitoes. The project will also help us to detect genome variations between these two species that may be important for speciation, adaptation, and vectoral capacity.",,2023,VIRGINIA POLYTECHNIC INST AND ST UNIV,237275,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22391,5R21AI148869-02,Elimination of flavivirus infected target cells by ADCC,"SUMMARY The development and widespread use of a dengue vaccine is required to significantly reduce the global dengue burden. A major goal of vaccine developers is to elicit robust immunity to each of the four antigenically distinct serotypes of dengue since all four serotypes can cause disease and death. It is likely that a zika virus vaccine will be available in the coming years. Pre-existing dengue virus immunity may impact the ability to generate an immunogenic zika vaccine. An improved understanding of the quality of Abs elicited during flavivirus infection is necessary as it is becoming clear that antibody function beyond neutralization is important. For this proposal, we will assess antibody dependent cell mediated cytotoxicity (ADCC) activity of antibodies present in well-defined zika immune sera (with and without previous dengue exposure). We have novel cell lines that enable us to assess the protein specificity of ADCC antibodies and also evaluate both target cell and effector cell activation. We will determine the relationship between antigen density and ADCC antibody titers in the sera. Finally, using pre-infection sera in individuals from Thailand who subsequently developed a subclinical or clinical dengue infection, we will correlate ADCC activity of antibodies with clinical outcome. The studies proposed are important to guide the development of an effective flavivirus vaccine.",,2023,UNIVERSITY OF RHODE ISLAND,196562,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22392,3U19AI111825-08S1,Integrating innate and adaptive pathways in vaccine responses,"ABSTRACT â€Â"" Overall Significant progress in basic immunology research over the last three decades has resulted in numerous medical advances and dissected the general mechanisms by which the human immune system responds to foreign antigens. However, a much more substantial understanding of the coordinated molecular mechanisms involved in eliciting immunity will be required, as each viral pathogen poses unique challenges to the immune system and the elicited immune responses are characterized by substantial heterogeneity that impacts disease susceptibility and pathogenesis. Indeed, it is expected that B-cell responses against diverse viral pathogens are uniquely evolved during infection to shape the functional activity of IgG antibodies. Studies from viral infectious diseases have shown that antiviral IgG antibodies have the capacity to mediate a wide spectrum of opposing functions: (i) protective functions, including neutralization, viral opsonization, and clearance of infected cells and (ii) pathogenic activities, which enhance viral infectivity, disease susceptibility and severity; a phenomenon termed as antibody-mediated enhancement (ADE) of disease. ADE mechanisms have been previously suggested to account for susceptibility to dengue disease, as epidemiological data support that prior flavivirus infection is the major risk factor for dengue disease, implicating the presence of cross-reactive, non-neutralizing IgG antibodies to this process. Understanding the heterogeneity of IgG responses elicited upon infection or vaccination with diverse viral antigens is therefore critical for characterizing the immunological mechanisms that drive human immunity and determine the protective vs. pathogenic activity of IgG antibodies. Our Center will feature three Projects directed by Drs. Ravetch (Project 1: Fc domain effector activity in dengue disease), Nussenzweig and Rice (Project 2: Understanding B cell memory in response to diverse virus infections), and Wang (Project 3: Immunity to dengue viruses), supported by a scientific core (Core A: Transgenic mouse core) and the administrative core (Core B). Through a series of collaborative studies between the three Projects, our Center aims to study human antiviral immune responses during infection and vaccination and characterize the immune mechanisms that regulate the function of IgG antibodies in humans. More specifically, we aim to characterize the heterogeneity of IgG responses elicited upon vaccination or infection with diverse viral pathogens, including HBV and flaviviruses, like Zika and dengue. Additionally, we will dissect the ADE mechanisms by which IgG antibodies mediate disease-enhancing activities and contribute to dengue disease susceptibility and pathogenesis. These studies will provide novel insights into the mechanisms that drive protective immunity and modulate antibody function, having a broader impact on the development of vaccination strategies against infectious pathogens.",,2022,ROCKEFELLER UNIVERSITY,1500000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +P22395,1R01AI154844-01A1,Essential early events in the flavivirus lifecycle,"Project Summary Arthropod-borne flaviviruses such as dengue virus, West Nile virus, yellow fever virus (YFV), and Zika virus, are a major cause of human disease. We are studying the early, post-fusion and pre-replication events in the flavivirus lifecycle by using the prototype flavivirus, YFV, as our model. Our overarching hypothesis is that flaviviruses, which alternately replicate in vertebrate and invertebrate hosts, have evolved to use i) highly conserved factors shared between hosts; and ii) multiple, redundant factors that may not be well conserved between hosts. Therefore, discoveries made with YFV will be validated and studied by comparison to other flaviviruses and between human and mosquito cells. Aim 1 focuses on the post-fusion process of nucleocapsid uncoating, dissecting the mechanisms by which cells unlock this fateful cargo. Aim 1 is a logical extension of our Preliminary Data showing that the delivery of a translatable YFV genome requires cellular ubiquitylation and VCP/p97, a cellular ATPase that extracts ubiquitylated proteins from large macromolecular complexes. Aim 2 focuses on identifying the cellular protease(s) that cleave the viral NS1-2A polyprotein intermediate. Cleavage is essential for flavivirus replication (shown here), yet the identity of this protease has remained elusive for over two decades. We have identified a small family of related candidate NS1-2A proteases and are validating their activity by rigorous, combinatorial genetic ablation. These efforts will solve long- standing puzzles in flavivirus gene expression and replication and identify targets for future development of broadly acting antivirals.",,2026,YALE UNIVERSITY,418750,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22396,5U01AI151807-02,Coordinating Research on Emerging Arboviral Threats Encoing the Neotropics (CREATE-NEO),"Project Summary In recent decades, Central and South America have experienced spillover of endemic arthropod-borne viruses (arboviruses) from wildlife reservoirs into humans, exchange and recombination of emerging arboviruses within the region, resurgence of arboviruses previously controlled by vaccination or vector control, introduction and spread of novel arboviruses, and exportation of viruses to other regions. Furthermore, there is great concern that newly-introduced Zika virus may spill back into an enzootic transmission cycle in the Americas. Central and South America encompass enormous vertebrate and invertebrate biodiversity, and these species harbor a broad range of arboviruses whose risk of spillover and spread in humans is presently unknown. Increases in the rates of global travel, invasion of novel vector species, urban expansion, deforestation, and global climate change all elevate the risk of further arbovirus emergence, as does the breakdown of public health structures in Venezuela. The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE- NEO) project will provide a network of surveillance sites in the neotropics coupled to cutting-edge modeling approaches in order to anticipate and counter emerging arboviruses. Aim 1 will identify novel and known arboviruses as well as the host-vector networks that sustain transmission of these viruses within the neotropics, map the spatial distribution of these transmission networks, and characterize virus transmission dynamics within these networks. To do so, we will collect mosquitoes and other vectors as well as non-human primates and other vertebrate hosts at multiple sites in areas of high and varied biodiversity in Panama and Brazil and screen these samples for known and novel arboviruses. These data will then be analyzed using niche modeling, machine learning to predict undiscovered hosts and vectors, and dynamical transmission models. Aim 2 will focus on prospective and retrospective analysis of human infection and disease. To do so, we will leverage ongoing human clinical cohorts at multiple sites in Brazil and Panama. We will extend and expand these cohorts, with a particular focus on the immune-mediated interactions among multiple arboviruses at sites of hyperendemicity. We will also develop novel diagnostics to capture known and novel arboviruses and model the impact of human and non-human primate movement on spillover and spillback of target arboviruses. Data and models generated via these two aims will forewarn local, regional and global public health agencies of arboviruses within Central and South America that pose particularly high risk of spillover, emergence into transmission among humans, and/or international spread. Moreover CREATE-NEO will build local capacity to predict, detect and respond to emerging arboviruses at their point of origin, thereby maximizing the potential to avert full-blown emergence.",,2025,UNIVERSITY OF TEXAS MED BR GALVESTON,1519214,Animals | Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Immunity | Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping,2020 +P22397,5R01AI143698-02,Understanding mosquito movement and its relevance to control through genetic analysis,"PROJECT SUMMARY/ABSTRACT: Dengue, Chikungunya, Zika and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. Consequently, there is interest in novel strategies to control these diseases, including the release of genetically sterile male mosquitoes, mosquitoes transfected with Wolbachia, and mosquitoes engineered with gene drive systems. The safety and effectiveness of these strategies and considerations regarding trial design and implementation are critically dependent upon a detailed understanding of mosquito movement at both fine and broad spatial scales, yet there are major gaps in our understanding of these movement patterns. The declining cost of genome sequencing and novel methods for analyzing geocoded genomic data provide opportunities to address these knowledge gaps. In this project, we propose to devise a robust approach for inferring fine-scale mosquito dispersal patterns and their impact on innovative vector control strategies. We propose to use in silico simulations of mosquito ecology and preliminary geocoded mosquito genomic data collected from Fresno, California to determine sampling routines capable of quantifying dispersal patterns, population sizes and mating patterns using genetic kinship analyses (Aim 1). Results from these analyses will iteratively inform sampling schemes for two rounds of subsequent collections of Aedes aegypti, the mosquito vector of dengue, Chikungunya and Zika viruses, in Yishun, Singapore (Aim 2). Genome sequencing and kinship analyses will be used to quantify Ae. aegypti movement patterns, population sizes and mating behaviors at this location, and to parameterize spatially-structured 3D models of Ae. aegypti population dynamics. The resulting models will be used to explore biosafety, trial design and implementation considerations for novel vector control strategies including: i) population suppression systems such as Wolbachia-infected males and genetically sterile males, and ii) population replacement systems such as population transfection with Wolbachia, localized systems such as chromosomal translocations, and non- localized systems such as homing-based gene drive (Aim 3). We expect the proposed research to lead to the development of greatly enhanced surveillance strategies to infer fine-scale mosquito movement patterns and other demographic parameters, and to help inform the safe application of several novel and highly promising strategies for the control of dengue, Chikungunya and Zika viruses and other devastating mosquito-borne diseases.",,2024,UNIVERSITY OF CALIFORNIA BERKELEY,561892,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22399,5R01AI151166-02,Metabolic basis of mosquito-endosymbiont-virus interactions,"PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.",,2025,COLORADO STATE UNIVERSITY,578163,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22400,3R01AI151166-02S1,Metabolic basis of mosquito-endosymbiont-virus interactions,"PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.",,2025,COLORADO STATE UNIVERSITY,41598,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22401,1R21AI153732-01A1,Monitoring mosquito eco-systems and vector-control strategies using a stand-off optical sensor.,"Monitoring mosquito ecosystems and vector-control strategies using a stand-off optical sensor. PI: B. Thomas â€Â"" NIH R21 Project Summary: Vector control strategies remain one of the most effective ways to protect human populations from the large number of mosquito borne diseases such as malaria, dengue fever, zika virus, or West Nile virus. Mosquito populations are generally monitored using physical traps, however this method suffers from many disadvantages. It requires long and expensive laboratory analysis by qualified personnel which drastically reduces the number of observed insects as well as time of trap deployment. Traps also provide a poor estimate of the actual population size or population density because the attractive range of traps is generally unknown and may change with weather conditions. These limitations are strong drawbacks in our ability to evaluate the effectiveness of various types of vector-control strategies (chemicals, biological, environmental modifications etc.). Inferior methods are not necessarily identified which ultimately contributes to the spread of infectious diseases. In this context, we argue that new methodologies to monitor insect population dynamics is key in the necessary effort to improve control program performance. A team from the New Jersey Institute of Technology in collaboration with the Hudson Mosquito Program seeks support to carry out a series of field experiments using a new optical sensor capable of identifying in real-time the family, species, and gender of mosquitoes in its field of view. The laser-based instrument is a dual-wavelength polarization-sensitive stand-off sensor. For each flying insect transiting through the infrared laser beams, the sensor can retrieve the optical properties of the wings and body of the insect as well as its wing beat frequency. Preliminary data from a laboratory prototype and numerical simulations indicate that the instrument, using a supervised machine learning classifier, can identify the species, gender, and gravidity of mosquitoes up to 300 m away. The instrument will be deployed in a high mosquito density area in New Jersey to continuously monitor the mosquito population over the whole season from April to October 2021. Continuous measurements will allow to identify a number of insects that is orders a magnitude higher than physical traps. As the probed volume of air is known, data analysis will provide the population density for each class of insects from which the population dynamics will be derived. In addition, the time and date of each insect transit allow to study the circadian rhythm, peak activities, and behavior as a function of atmospheric conditions measured by a weather station. In 2022, a similar experiment will be conducted at the same location while the Hudson Mosquito Program will conduct a vector control campaign targeting Culex and Aedes mosquitoes, both responsible for the spread of various infectious diseases. The impact of multiple applications of airborne pyrethroid insecticide on targeted and non-targeted insects will be evaluated by studying the mortality rates and population dynamics for each species. Both years, the data will be compared to physical traps on site, the current gold standard method, for further analysis and validation.",,2023,NEW JERSEY INSTITUTE OF TECHNOLOGY,187106,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P22403,1R21AI159459-01,Non-invasive approaches to mosquito-borne pathogen surveillance using excreta,"Project Summary Mosquito-borne diseases are expanding rapidly across the globe. Recent outbreaks of West Nile, dengue, chikungunya and Zika viruses have sickened hundreds of millions of people, while parasites such as malaria kill over 400,000 annually. The spread of competent vectors and their pathogens to new continents and climates, coupled with the recent rapid global expansion of other novel RNA viruses that infect humans, emphasizes the need for rapid and reliable pathogen surveillance techniques now more than ever. Early detection ensures that vector control efforts are directed to the right location at the right time to avert a potential epidemic. Surveillance and detection of infected mosquitoes is often an early predictor of impending human infection however comes with challenges, including the time involved to sort, identify and extract RNA from large numbers of mosquitoes while maintaining a cold chain. This requires that mosquito surveillance, identification, and pooling precede virus testing. It has recently been shown that mosquitoes with a disseminated infection excrete (as excreta/feces) arbovirus and parasites in concentrations suitable for detection when sampled in the lab. This allows for rapid and non-destructive sampling and pathogen testing, however current field trapping devices are unable to efficiently collect the randomly distributed ca. 1.5 Ã'µL excreta droplets. To address this issue, we propose here to design two novel excreta-collecting mosquito traps for host-seeking and ovipositing (or gravid) mosquitoes, respectively, that utilize sugar feeding stations and a custom fabricated collection system composed of a nanostructured superhydrophobic surface to funnel and condense the excreta sample. An appropriate hydrophobic surface conformation will first be selected and tested for efficacy during initial field trials. This prototype will then be scaled up and configured to trap wild mosquito populations while channeling and aggregating excreta produced within the trap to a standard microcentrifuge tube attached externally for quick and easy collection. To test the ability of both devices to effectively sample potential pathogens from trapped mosquitoes, the traps will be deployed across five New Jersey counties spanning a multitude of mosquito habitat in collaboration with county mosquito control agencies. The captured excreta will be subject to metavirome sequencing to identify and assemble genome data from the full breadth of both known and potentially novel RNA viruses in the samples, representing a broad diversity of New Jersey mosquitoes. This project represents a foundational step towards sentinel “mosquito free” surveillance of vector-borne pathogens that will facilitate rapid response to mitigate enzootic outbreaks before they occur.",,2023,"RUTGERS, THE STATE UNIV OF N.J.",170965,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P22405,5R21AI146528-02,Chromosomal rearrangements in arboviral vector Aedes aegypti,"PROJECT SUMMARY Aedes aegypti transmits several arboviral diseases, including dengue and Zika fever, which threaten virtually half of the world’s population. Two subspecies, Ae. aegypti aegypti (Aaa) and Ae. aegypti formosus (Aaf), have been described based on their body coloration. These two subspecies differ remarkably from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. In Anopheles populations, polymorphic inversions are often responsible for epidemiologically important phenotypes but our knowledge about chromosomal rearrangements in Aedes populations is scarce. So far, only two chromosomal inversions have been directly observed in chromosomes of Ae. aegypti from Senegal. Based on our preliminary data, we hypothesize that chromosomal inversions are abundant in Ae. aegypti and are involved in the establishment and maintenance of genomic and phenotypic divergence in natural populations of this mosquito. In this study, we will take advantage of a dramatically improved, fully re-annotated genome assembly for Ae. aegypti and employ the Hi-C approach along with Oxford Nanopore Technology (ONT) sequencing to characterize chromosomal rearrangements. [The primary goal of this R21 proposal is to identify chromosomal rearrangements in aedine mosquitoes]. Toward this end, we propose three specific aims: 1) characterize chromosomal rearrangements in 16 strains of Aaa and Aaf from various worldwide populations using the Hi-C approach; 2) develop a high-quality de novo genome assembly for the Aaf Uganda strain using advanced genome technologies; and 3) develop PCR and FISH-based approaches for identification of the 3p2 chromosomal inversion, which is potentially of medical importance. The innovative strategies of using Hi-C analysis and ONT sequencing will make possible the discovery of chromosomal inversions in Ae. aegypti and will stimulate future genetic studies aimed at preventing mosquito-borne disease transmission.",,2023,VIRGINIA POLYTECHNIC INST AND ST UNIV,188068,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +P22409,1R01AI155959-01,"Sample-to-Answer, Rapid, Multiplexed and PCR-Free Diagnostics of Arboviral Diseases in Resource Limited Settings","Arthropod-borne viruses (arboviruses) comprise many of the most important ‘emerging pathogens’ due to their geographic spread and their increasing impact on vulnerable human populations. There is urgent need for easy-to- operate and rapidly deployable diagnostic tools that can handle blood samples in a closed sample-to-answer manner. Here, we propose to develop a novel diagnostic technology that can detect viral antigens in an inexpensive, ultrasensitive, specific, and multiplexed manner. We will develop our novel approach into standalone tool with a detection capability at attomolar sensitivities (comparable to nucleic acid amplification tests) to diagnose arboviral infections with minimal user interference. The integrated diagnostic platform will utilize a novel surrogate approach, microfluidic integration, and a multiplexed detection scheme with the capacity to distinguish arboviral infections. The system will be designed to initiate diagnosis from serum/plasma/blood and provide a sample-to-answer diagnostic within less than 35 minutes using less than 100 Ã'µL blood samples at a cost of $2 per test. Collaborative work proposed for this NIH/NIAID R01 Grant involves integration of nanophotonic engineering (Yanik Group), molecular virology (Pinsky Group), and infectious diseases epidemiology (LaBeaud Group) to build and field-test our novel point-of-care viral diagnostic platform with Windward Islands Research and Education Foundation (WINDREF) and St. George’s University teams (Macpherson, Waechter and Noel Groups). Preliminary validation tests with patient samples will be initially performed at Stanford Medical Facility in collaboration with LaBeaud and Pinsky groups. Subsequently, three prototypes will be transferred to Grenada for field-testing initially at central laboratories then to resource-poor settings in small towns. Yanik group will provide the necessary expertise for integration of molecular and nanoengineering components and demonstration of a practical prototype as well as evaluating the application of prototype(s) developed under this proposal with patient samples (LaBeaud and Pinsky Groups). System will be iteratively optimized and a rugged platform suitable for field settings will be developed.",,2025,UNIVERSITY OF CALIFORNIA SANTA CRUZ,771450,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P22410,75N93019C00062-P00012-9999-1,"B Cell Epitope Discovery and Mechanisms of Antibody Protection: Responses to Dengue 4, Powassan, Chikungunya, and Venezuelan Equine Encephalitis Viruses ","This contract supports the identification of human B cell epitopes derived from four viral pathogens; Dengue virus 4, Powassan virus, Chikungunya virus, and Venezuelan equine encephalitis virus, combined with basic studies to understand protective immunity mediated by antibodies, as well as pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. The primary goal of this contract is the delineation of B cell epitopes recognized by potently neutralizing or protective antibodies and evaluation of correlates of protection that can aid in the development of vaccines and therapeutics against select arthropod-transmitted viruses. The Contractor has chosen two flaviviruses (Dengue virus 4 and Powassan virus) and two alphaviruses (Chikungunya virus and Venezuelan equine encephalitis) for primary investigation of antibody responses to viral glycoprotein antigens. The Contractor will also evaluate protective antibodies that recognize the flavivirus nonstructural protein 1 (NS1) produced by West Nile and Zika viruses.",,2022,WASHINGTON UNIVERSITY,1722037,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22411,1R21AI156078-01,Development of precision genome editing tools in Ae. albopictus for functional genetics and mosquito control technologies,"PROJECT SUMMARY The Asian tiger mosquito, Aedes albopictus, is an aggressive human-biting mosquito that is a competent vector of the dengue, chikungunya and Zika viruses as well as multiple native North American encephalitis viruses. The rapid spread of this mosquito from its native Asian range across the globe during the last 30 years and its well- established role as a primary vector of recent outbreaks of both dengue and chikungunya viruses represents an outstanding public health concern. The goal of this proposal is to produce and test a flexible and efficient precision genome editing system based on CRISPR-Cas9 in A. albopictus. We propose to produce multiple transgenic lines with stable germline expression of the Streptococcus pyogenes Cas9 protein (Cas9) driven by native A. albopictus promoters. Our rationale is that endogenously expressed Cas9 leads to higher editing rates, greater technical efficiency and dramatically decreased costs of genome editing relative to injection of exogenous sources of Cas9. This rationale is supported by our previous work in another closely related vector, Aedes aegypti, where the production of endogenous Cas9 lines not only improved functional genetic capabilities in this vector, but also provided the foundation for the development of genetic-based control technologies. In aim 1, we will produce transgenic lines with native A. albopictus promoter sequences driving Cas9 expression and fluorescent reporters. These lines will be rationally designed based on recent “omics” data in A. albopictus and our extensive work in another closely related vector. Lines will be tested that have different Cas9 promoters and insertion sites and lines with the most robust and stable Cas9 expression will be more extensively evaluated in single and multi-gene knockout studies. In aim 2, we will design and test small guide RNAs to target multiple genes of potential relevance to A. albopictus control including potential phenotypic markers for quality control and sex sorting applications, sex determinate genes and flight specific genes for sterile insect techniques and gene drive applications as well as essential genes of interest for gene drives. The research described in this proposal will advance A. albopictus genomics research by: (1) establishing a platform for rapid and efficient functional genetics and reverse-genetic screens of genes affecting a wide range of phenotypes relevant to disease transmission and vector control, and (2) completing a necessary first step to develop novel tools for vector control such as genetic sexing and gene drive.",,2023,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",236750,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector control strategies,2021 +P22413,1R56AI155573-01A1,A functional and comparative approach for the study of Wolbachia-mediated virus blocking in Aedes aegypti and Aedes albopictus,"PROJECT SUMMARY/ABSTRACT The global range of the mosquito, Aedes aegypti continues to expand due to a changing climate and increasing urbanization. As Ae. aegypti is the primary vector of dengue, Zika, yellow fever and chikungunya viruses, these range shifts also increase the risk of human disease. With few effective vaccines or antiviral drugs, vector control remains the best weapon against mosquitoes. Recently, the release of an insect endosymbiont, Wolbachia, into mosquito populations has emerged as a novel biocontrol strategy. Maternally inherited and with inbuilt genetic drive, Wolbachia tends to spread through insect populations. Inside the mosquito, the bacterium limits the replication of viruses, a trait called ‘viral blocking’. Following release of Wolbachia into wild populations, the viral blocking effect is leading to substantial reductions in the incidence of dengue fever in humans. One concern for the long- term efficacy of Wolbachia is the emergence of resistance in mosquitoes or viruses. To design strategies to counter this likely scenario, we need to understand the genetic basis of viral blocking. While many theories have been proposed, none have been entirely satisfying. Recently, the McGraw lab used a selection experiment to create Ae. aegypti lines carrying Wolbachia with differences in blocking. In sequencing those lines, her group identified a set of novel candidate loci and a new set of hypotheses for the basis of blocking. This study also demonstrated that the strength of blocking is likely to vary across diverse mosquito genetic backgrounds. Here we propose to provide functional testing for the candidate blocking genes involved with cell adhesion, transcriptional pausing and neuronal function, for both dengue and chikungunya viruses using RNA silencing. In these experiments we will also contrast Aedes albopictus, that has long harbored a natural infection of Wolbachia, against Ae. aegypti with a recently artificially introduced Wolbachia. The nature of blocking in Ae. albopictus is a likely harbinger of the future of blocking in the artificially infected species. We will also carry out large common garden experiments to dissect the relative contribution of regional differences in mosquito and virus diversity to the strength of blocking. This project will produce novel resources for the community including a new Wolbachia infected Ae. aegypti line, a set of antibodies against key blocking association proteins and data on the efficacy of improved fluorescent reporter viruses for the study of vector competence. More broadly, this research will help to test a revised model for Wolbachia-mediated viral blocking â€Â"" knowledge fundamental for designing strategies to prolong Wolbachia’s efficacy in the field. It will also reveal the robustness of blocking to mosquito and viral genetic diversity, that will inform strategies for future Wolbachia strain deployment globally.",,2024,"PENNSYLVANIA STATE UNIVERSITY, THE",491795,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P22414,5U01AI151788-02,American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES),"ABSTRACT Recent pandemics of human pathogens have revealed the limitations of current surveillance systems. The sequential arboviral epidemics in the Americas showed how outbreak detection can be delayed and opportunities missed to collect well-characterized specimens and data for surveillance, basic science, clinical research, and development of vaccines and new diagnostics. In response, we have assembled a consortium of world-renowned investigators in arbovirology, epidemiology, immunology, viral diagnostics, phylogenetics, and clinical research, while leveraging research infrastructure and expertise in long-term cohort and hospital-based studies. This has resulted from 3 decades of collaborative international research, with over 200 joint publications, and extensive experience in preparing for and responding to outbreaks working closely with local and international health authorities and NIAID. With key sites in Asia and the Americas, we will use innovative molecular and serological methods to identify emerging pathogens and to address fundamental questions in dengue and other arboviral epidemiology and test viral, host and environmental determinants of differences between sites along a gradient of urbanicity. Our overarching goal is to develop an interconnected, harmonized network of clinical and laboratory sites to strengthen research programs, compare disease epidemiology and severity in different regions, develop and implement cutting-edge diagnostic methods, and respond efficiently and effectively to outbreaks. Standardized hospital studies and community-based cohorts in Ecuador, Nicaragua and Sri Lanka will characterize and compare human arboviral illnesses across urban, peri-urban and rural sites and develop sustainable infrastructure to rapidly respond to epidemics together with Ministries of Health, comple- mented by outbreak investigation, surveillance of non-human primates, and vector incrimination. We will imple- ment standardized plans for study administration, data and clinical management, and statistical analysis across sites, supported by an extensive on-site training program. Aim 1 will establish standard and novel multiplex assays at each site for surveillance, diagnosis and research of arboviruses and other pathogens. Aim 2 com- pares dengue/arbovirus epidemiology and transmission in cohort studies located in ecologically distinct regions over a continuum of urbanicity. In Aim 3, we will characterize complete viral genome sequences for comparative studies of arboviral phylogenetics, phylogeography and molecular epidemiology. Aim 4 consists of surveillance, identification, and characterization of novel and unrecognized human pathogens from severe hospitalized cases, unexpected outbreaks, vectors and non-human primates. Molecular and serological assays will be developed for newly identified pathogens and quickly implemented across study sites to characterize the epidemiology and clinical manifestations and will be made available to the EIDRC network. In sum, our A2CARES Consortium will provide valuable new tools and knowledge and 3 interconnected centers in Latin America and South Asia that will be able to respond to outbreaks and to study emerging and endemic infectious diseases far into the future.",,2025,UNIVERSITY OF CALIFORNIA BERKELEY,1575273,Viruses,Not applicable,Not Applicable,Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Novel Pathogen | Unspecified,,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease transmission dynamics | Disease surveillance & mapping",2020 +P22418,3U01AI151788-02S1,American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES),"ABSTRACT Recent pandemics of human pathogens have revealed the limitations of current surveillance systems. The sequential arboviral epidemics in the Americas showed how outbreak detection can be delayed and opportunities missed to collect well-characterized specimens and data for surveillance, basic science, clinical research, and development of vaccines and new diagnostics. In response, we have assembled a consortium of world-renowned investigators in arbovirology, epidemiology, immunology, viral diagnostics, phylogenetics, and clinical research, while leveraging research infrastructure and expertise in long-term cohort and hospital-based studies. This has resulted from 3 decades of collaborative international research, with over 200 joint publications, and extensive experience in preparing for and responding to outbreaks working closely with local and international health authorities and NIAID. With key sites in Asia and the Americas, we will use innovative molecular and serological methods to identify emerging pathogens and to address fundamental questions in dengue and other arboviral epidemiology and test viral, host and environmental determinants of differences between sites along a gradient of urbanicity. Our overarching goal is to develop an interconnected, harmonized network of clinical and laboratory sites to strengthen research programs, compare disease epidemiology and severity in different regions, develop and implement cutting-edge diagnostic methods, and respond efficiently and effectively to outbreaks. Standardized hospital studies and community-based cohorts in Ecuador, Nicaragua and Sri Lanka will characterize and compare human arboviral illnesses across urban, peri-urban and rural sites and develop sustainable infrastructure to rapidly respond to epidemics together with Ministries of Health, comple- mented by outbreak investigation, surveillance of non-human primates, and vector incrimination. We will imple- ment standardized plans for study administration, data and clinical management, and statistical analysis across sites, supported by an extensive on-site training program. Aim 1 will establish standard and novel multiplex assays at each site for surveillance, diagnosis and research of arboviruses and other pathogens. Aim 2 com- pares dengue/arbovirus epidemiology and transmission in cohort studies located in ecologically distinct regions over a continuum of urbanicity. In Aim 3, we will characterize complete viral genome sequences for comparative studies of arboviral phylogenetics, phylogeography and molecular epidemiology. Aim 4 consists of surveillance, identification, and characterization of novel and unrecognized human pathogens from severe hospitalized cases, unexpected outbreaks, vectors and non-human primates. Molecular and serological assays will be developed for newly identified pathogens and quickly implemented across study sites to characterize the epidemiology and clinical manifestations and will be made available to the EIDRC network. In sum, our A2CARES Consortium will provide valuable new tools and knowledge and 3 interconnected centers in Latin America and South Asia that will be able to respond to outbreaks and to study emerging and endemic infectious diseases far into the future.",,2022,UNIVERSITY OF CALIFORNIA BERKELEY,175562,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Novel Pathogen | Unspecified,,,,,,,,,Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease transmission dynamics | Disease surveillance & mapping",2021 +P22419,5R01HL153073-02,Transfusion-related immunomodulation influences infectious disease outcomes,"Project Summary/Abstract Transmission of acute viral infections through blood transfusion during large epidemics is a serious public health issue, particularly for newly emerging infections for which no sensitive FDA-approved tests are available. Arboviruses can be serious acute infections leading to serious long-term complications, and are noted for their massive epidemic, as recently demonstrated with first chikungunya virus (CHIKV) and then Zika virus. Despite possessing many of the characteristics required for blood transfusion transmission (TT), such as high loads of infectious virus in blood and the ability to infect via intravenous inoculation, there have never been any CHIKV TT events reported. This is despite large-scale epidemics where up to 2% of blood donations have been found to be RNA reactive. We have preliminary data supporting the fact that CHIKV can be transfusion-transmitted in mice, and that transfusion of RBC attenuated CHIKV pathogenesis. The central hypothesis behind this study is that TT does occur, however a number of factors drive infection towards being asymptomatic or mild. Further, immune modulation during transmission, in this case via the blood transfusion itself, leads to an attenuation of disease. Specifically, we and others have demonstrated a number of innate immune factors are both modulated by transfusion and able to alter CHIKV outcomes. These include innate lymphoid cells and regulatory T cells and the cytokines both upstream and downstream of their stimulation. This study will use a murine model of CHIKV pathogenesis to investigate these findings further. Additionally, it will mimic blood transfusions, TT of CHIKV, and study immune parameters and disease outcomes. Beyond understanding the interplay between pathogenesis and blood transfusion, these studies will have a wider impact on acute viral infections in general. It is likely that similar immune factors can have dramatic effects on viral replication and/or pathogenesis, and thus a deeper understanding of how these mechanisms are mediated will allow better planning for screening efforts and potentially even interventions during serious epidemics. This will allow improved capabilities and decision making in responding rapidly to a new viral threat to blood safety and availability.",,2024,VITALANT,612357,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P22424,5R01AI151004-02,Precision guided SIT for the control of vector-borne disease,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases. Dengue alone causes 90 million infections per year globally and like many vector-borne diseases, currently there are no drugs or vaccines to treat or prevent these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. In recent years, novel vector population suppression technologies have been created (e.g. RIDL and Wolbachia based systems), but production of mosquitoes for these programs is labor intensive and is limited in scalability and distribution. In this study, we will use a functional genomic screening approach to identify key sex determinate, female essential (FE) and male fertility (MF) genes in the dengue vector, Ae. aegypti. These studies will improve our understanding of the biology of this important vector and it can be used to inform the design of new genetic population suppression methods to control this vector. After these genes are identified and characterized, we will incorporate them into the design of precision guided sterile insect technique (pgSIT) technologies in an attempt to overcome limitations in traditional SIT control strategies. Sterile insect technique (SIT) is the gold standard for insect population control but has many limitations. Our proposed technology aims to simultaneously knock-out FE and MF genes using a binary CRISPR/Cas9 system in the Ae. aegypti disease vector. One line will target one or more female essential FE genes and one or more MF genes and the other line will express a Cas9. When these two lines are crossed, they create sterile, male progeny that are ready for release into a population suppression program. To generate these lines, initially we will characterize >40 candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be determined over many generations to ensure population stability. The design and integration of these transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression systems, including the impact of transgene expression timing and transgene location on the long-term stability of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies. In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",461219,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P22425,5R01AI151029-02,Next Generation Resolution of Antiviral Gene Networks,"SUMMARY As the primary mediators of the innate response to viral infection, type I interferons (IFN-I) establish an antiviral state in both infected and uninfected bystander cells through the induction of several hundreds of interferon stimulated genes (ISGs). The mechanisms by which the coordinated activities of these ISGs confer resistance to diverse viruses, and the regulatory circuits that modulate their expression remain poorly understood. Working with unique samples from individuals with hereditary syndromes of dysregulated IFN-I responsiveness, we have identified a collection of thirty ISGs that confer resistance to diverse viruses (increased protection against RNA and DNA viruses with both high and low pathogenic burden). We have also uncovered previously unappreciated negative feedback mechanisms of IFN-I signaling. We have found that these regulatory circuits, as well as ISG expression patterns, vary significantly across different cell types at steady state and upon IFN-I stimulation. Recent technological advances now enable us to explore these cooperative ISG antiviral functions and negative feedback mechanisms at unprecedented depth and resolution. In the studies proposed here, we will identify subsets of ISGs sufficient to confer broad protection against multiple viruses using a novel single cell RNA-Seq strategy. This approach provides the throughput required to conduct complex combinatorial experiments while maintaining the high resolution to test specific hypotheses. Results may offer new broad spectrum antiviral therapeutic strategies, which would be of particular value against emerging viral pathogens. We will also investigate in detail the mechanisms by which IFN-I signaling establishes a lasting imprint on cellular responsiveness to subsequent IFN-I stimulation. This recently described but incompletely characterized phenomenon likely has important implications for successive infectious challenges and viral susceptibilities. Combining a unique collection of clinical samples, cutting edge technologies, and diverse and complementary expertise in immunovirology from our two laboratories, these studies are expected to address long standing, fundamental questions in innate antiviral immunity, as well as to pioneer new directions for developing antiviral therapies.",,2025,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,662018,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +P22426,1F31AI154824-01A1,Scalable Inference in Statistical Models of Viral Evolution and Human Health,"Project Summary / Abstract Despite global public health advances, viruses remain a major threat to human health both in the United States and internationally. Recent and continuing outbreaks of SARS-CoV-2, Ebola, Zika, Lassa fever, and Chikungunya, as well as persistent epidemics such as HIV have emphasized the need to understand viral evolution and virus-host interactions during epidemics. Phylogenetic statistical models of viral evolution offer a powerful tool for studying the interplay between viral genetics and environmental or host factors. However, current phylogenetic models are often too inï¬Â'exible to realistically model these relationships, and those that do are computationally intractable for even moderately sized data sets. This project aims to develop new statistical models that are both ï¬Â'exible enough to model complex biological relationships and scalable to large data sets of viral and host traits. The first aim is to develop more efficient and less biased statistical methods for estimating the heritability of viral phenotypes (e.g. viral load, host CD4 T-cell count, replicative capacity). Current statistical practices typically produced biased heritability estimates and are intractable for large data sets. This project seeks to extend state-of-the-art inference techniques to model the heritability of viral pheno- types (enabling both unbiased and efficient inference) and to apply these new methods to better estimate the heritability of viral load in HIV-1. The second aim seeks to develop statistical methods for studying complex, high-dimensional viral phenotypes such as infection severity which cannot be captured with a single measure- ment. These phenotypes are difficult to quantify due to their inherent complexity, confounding rigorous efforts at, say, identifying unusually virulent viral clades. While phylogenetic factor analysis enables identification and quantification of high-dimensional phenotypes, it scales poorly to large data sets. We propose new inference techniques that address these scalability problems and allow previously intractable analyses. We plan to apply these new methods to study patterns of virulence in Ebola and Lassa fever and to identify unusually virulent viral strains. Additionally, these methods are well suited to identifying epistatic interactions between viral mu- tations and phenotypes of interest, and we plan to explore these interactions in HIV, Zika, and Chikungunya viruses. The third aim is to develop new statistical models specifically designed to predict outcomes of viral infections from viral sequence data. To accommodate the necessary ï¬Â'exibility required by these models, we develop new inference strategies that are both highly generalizable (i.e. they do not rely on strict assumptions in existing models) and computationally efficient. Strong predictive performance would enable researchers or clinicians to predict clinically relevant outcomes using viral sequences, which could help inform treatment. We will evaluate these methods using the Ebola and Lassa fever data from mentioned above.",,2023,UNIVERSITY OF CALIFORNIA LOS ANGELES,37853,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae | Flaviviridae,,,,,,,,,Lassa fever | Ebola virus disease | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P22428,1R01AI165560-01,Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats,"Project Summary Each year, approximately 400 million people are infected with an arboviral disease from the bite of an Aedes spp mosquito. Aedes spp. mosquitoes are a leading public health threat due to their high competency to vector multiple pathogens, their preference to bite humans, and their ability to adapt to new domestic environments. In the US, reintroduction and establishment of Aedes aegypti and Aedes albopictus mosquito populations has resulted in local epidemics of Zika, dengue and chikungunya in the past decade. Unfortunately, mosquito control programs in the US generally operate with limited budgets, forcing the majority of insecticide spraying to be conducted in reaction to population exposure instead of targeted prevention, which has also contributed to considerable growth of insecticide resistant populations, yielding a widening gap of infrastructure vulnerability. Our current proposal aims to leverage existing technologies from non-health disciplines to advance mosquito detection and abatement. We propose to validate the use of technology-driven mosquito traps that allow for high- throughput identification and counting of Aedes mosquitos at various life stages to inform decision making when selecting areas for insecticide spraying and abatement. Additionally, we propose to develop rigorous remote sensing workflows for identification of neighborhood-level Aedes abundance risk and rapid detection of individual Aedes mosquito breeding habitats on a household-level. This innovative proposal uses multi-year and real-world mosquito data from two different metropolitan areas to statistically adjust for variances in geographic ecologies, urban microclimates, seasonal climate patterns, and annual weather events. Our study will result in low-cost tools immediately ready for broad distribution and integration by vector control agencies nationally. The outcomes of our study have promise to directly impact vector control agency’s decision-making processes for mosquito trapping site selection, inform preventative abetment protocols, and shorten the time required for mosquito collection and identification. Further, integration of our proposed technology traps and informed site selection maps will increase overall collection volumes while preserving scarce resources for local vector control agencies. This proposal has the potential to create a paradigm shift in how we approach vector control globally, with a targeted intervention resulting in significant economic, environmental, and clinical benefits.",,2026,UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA,782998,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P22431,1R01AI150672-01A1,Dengue virus mRNA lipid nanoparticle vaccine,"Nearly 400 million people are infected with dengue virus (DENV) each year through the bite of infected mosquitos concentrated in the tropical and subtropical regions of the world. Symptoms can range from febrile illness to severe dengue that manifests as plasma leakage, sudden loss of blood pressure, organ failure, and shock that can ultimately lead to death. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross- reactive, poorly-neutralizing epitopes lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). Additionally, DENV immunity has been implicated in increased susceptibility to Zika virus through ADE. Currently there are no available therapeutics to combat DENV disease. Dengvaxia, the only licensed DENV vaccine, was found to increase hospitalization rates in naïve populations, and thus is not recommended for a large portion of at-risk individuals. There is an urgent need for a safe and efficacious vaccine that elicits a robust, balanced, neutralizing response to all four DENV serotypes. We propose to develop a novel DENV vaccine utilizing an emergent platform: mRNA encoding for viral proteins encapsidated in a lipid nanoparticle (LNP). mRNA-LNP vaccines elicit robust humoral and cell-mediated immune responses in a safe, non-infectious platform. Additionally, we can direct the host immune response towards neutralizing epitopes by mutating the mRNA encoding for the viral protein. We hypothesize that a sequence-engineered tetravalent mRNA-LNP vaccine will induce a balanced, protective immune response against all four serotypes of dengue without the potential of causing immune enhancement and ADE. In Aim 1 of this study we will generate and optimize mRNA constructs encoding for the pre-membrane and envelope viral glycoproteins for all four serotypes of DENV. We will mutate the poorly-neutralizing, cross-reactive epitopes that drive ADE. In Aim 2 we will characterize the immune response to the vaccines in a mouse model. In addition to quantifying humoral and cellular immune responses, we will also measure the immune enhancement capacity of all vaccines. In Aim 3, we will evaluate vaccine efficacy and safety in susceptible mouse models, by challenging vaccinated mice with different DENV serotypes to monitor protection and ADE. We will also determine mechanism of protection via adoptive transfer experiments. Through this study, we will identify DENV vaccines that demonstrate broad protection and lack of immune enhancement for further evaluation as candidate human vaccines.",,2025,UNIVERSITY OF ILLINOIS AT CHICAGO,454113,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +P22432,1F31AI152453-01A1,Identification of Flavivirus Nucleocapsid Core-Envelope Glycoprotein Interactions,"Project Summary/Abstract Flaviviruses (a family of over 90 known viruses, including Zika, dengue and West Nile) are significant human pathogens affecting 3.1 billion people annually, and most of these enveloped viruses do not have any viable vaccines or antivirals capable of combating their spread. The primary objective of current flavivirus antiviral design is to disrupt specific mechanisms in the flavivirus life cycle that are key for virus survival, including virus attachment to the host cell, viral endocytosis, genome uncoating, genome replication, and virus maturation through the Golgi. These potentially druggable mechanisms have been explored in great detail both within our lab and elsewhere. However, little is known about the assembly mechanisms that drive infectious virus particle formation. Because of the high structural homology among all flaviviruses, the identification of assembly mechanisms will provide ubiquitous targets for therapeutic intervention in virus proliferation. In other enveloped virus systems, assembly depends on the interaction of virus core proteins with lipid membranes or membrane bound glycoproteins to produce infectious virus particles. Exploration via single particle Cryo-EM reconstruction has shown that the nucleocapsid core (NC) of immature Zika virus, is found in close proximity with the envelope glycoproteins on the inner side of the virus’s lipid bilayer. Due to this close proximity, I hypothesized that the NC interacts with the envelope glycoproteins during virus assembly. I further hypothesized and that these interactions occur between the capsid protein (CP) and transmembrane helices of the precursor membrane (prM) protein and the envelope (E) protein while the particle is in the immature state. Since no information currently exists on virus assembly relying on CP-prM/E interactions, these interactions have the potential to be exploited as new drug targets capable of inhibiting the proliferation of flaviviruses. To this end, I am investigating two independent strategies to validate the hypothesized NC-prM/E interactions using dengue virus serotype 2 (DENV2) as a model system. The Kuhn lab is particularly adept in mutagenesis studies using DENV2, which is why the decision was made to use this virus as our model system instead of Zika. Firstly, amino acids within the prM/E transmembrane helices that were posited to be key in the assembly process of DENV2 and other flaviviruses have been or will be mutated to investigate their role in promoting particle assembly. Secondly, the ability of the DENV2 prM and E transmembrane helices to interact with CP is being examined through the use of reconstituted prM and E proteins within SMA lipid nanoparticles. Due to the high similarity of all flaviviruses, the techniques, results and mechanisms identified in this study can be applied to other flaviviruses. Combining these essential experimental studies with the proposed training skills and collaborative opportunities for effective scientific communication through writing, speaking and mentoring will prepare me well for a future in biomedical research.",,2022,PURDUE UNIVERSITY,36942,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22435,5F32AI150123-02,Flavivirus cellular tropisms driving dissemination and transmission in mosquito vectors,"Project Summary/Abstract The research objectives of this fellowship are to determine the cellular tropisms of three mosquito-borne flaviviruses of public health importance â€Â"" Zika virus, dengue virus and yellow fever virus â€Â"" within their Aedes aegypti vectors and to define the roles of specific cell populations in viral dissemination and transmission. The aims are to 1) identify the specific cell populations critical for viral dissemination from the midgut to the salivary glands, and 2) define the impact of specific tissue tropisms on mosquito feeding behavior and viral transmission. Aim 1 will be accomplished by generating microRNA (miRNA) expression profiles for midgut, hemocyte and neuronal cell populations and selecting miRNAs that are highly differentially expressed in each population. We will confirm infection of cells expressing these miRNAs and generate cell-specific, miRNA-restricted viruses containing target sequences for cell-specific miRNAs to probe the roles of each cell type in viral dissemination. Aim 2 will be accomplished by using miRNA-restricted viruses to determine the effect of neuronal cell and salivary gland infection on mosquito feeding behaviors and subsequent transmission of the virus by observing infected mosquitoes feeding on mice and testing mice for the presence of virus. The data and tools produced by this work could aid the development of transmission control strategies that target viral replication in specific cell populations within the vector. Research and postdoctoral training activities will be undertaken at both Colorado State University and the Centers for Disease Control and Prevention in Fort Collins, CO. The sponsor and co- sponsor laboratories have complimentary research interests and facilities that will promote the success of this project. In addition to research, the training plan includes completion of coursework in next generation sequencing experiment and analysis, grant writing, and responsible conduct of research; participation in supervisory training; and attendance at various workshops, seminars and conferences to improve writing, presentation and career building skills.",,2023,COLORADO STATE UNIVERSITY,66390,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22436,5R01AI153064-02,Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses,"ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no effective vaccines are available. Protective immunity against many pathogens can be achieved through long- lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly, our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.) Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced immune mechanisms that regulate the biology of Tfh cells. This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and durable neutralizing antibody responses. This finding could have a significant impact on vaccine development as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable protective antibody responses against many pathogens. We believe that the data generated in this proposal will be capable of moving this vaccine adjuvant towards clinical trials.",,2024,UNIVERSITY OF PENNSYLVANIA,633178,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22438,7R01AI146152-03,Validating the Flavivirus Envelope Protein as an Antiviral Target,"PROJECT SUMMARY Dengue virus (DENV) and other flaviviruses are major human pathogens that cause significant disease. Transmitted by widespread mosquito species, many of these viruses spread rapidly and can have a devastating impact on public health where prior immunity does not exist. There is thus a significant need for countermeasures to combat both current and future flavivirus threats. Major limitations in current antivirals development are the relatively small number of validated antiviral targets, most of which are viral enzymes (e.g., polymerases, proteases); the low barrier to resistance when direct-acting antivirals are used as monotherapies; and the narrow spectrum activity of most of these agents (“one bug, one drug”). New classes of targets that can mediate broad-spectrum activity against related viruses and that have high barriers to resistance are particularly needed to combat emerging viruses since we generally lack sufficient time and resources to develop new drugs on a useful time scale once these viruses pose significant threats. Small molecules targeting the flavivirus envelope protein, E, have the potential to mimic the humoral immune response by engaging their target extracellularly and blocking viral entry early in the replication cycle. We have identified multiple small molecule inhibitor series that bind to the DENV envelope protein, E, and inhibit E-mediated membrane fusion during viral entry even when only a minority of copies of E on the particle are inhibitor-bound. These compounds bind in a pocket between domains I and II and inhibit West Nile, Zika, and Japanese encephalitis viruses due to at least partial conservation of this site. We recently established a target-based assay and validated its use in the identification of new inhibitors of DENV and Zika E proteins that bind in the conserved pocket and that have more drug-like properties than our original inhibitors. Building on this work, we now propose a comprehensive plan to rationally optimize small molecule inhibitors of the DENV E protein as a potential anti-viral strategy. Towards this end, we will combine modeling and structure- guided drug design with an efficient screening cascade using complementary target-based biochemical, cellular and mechanistic assays to enable efficient optimization of two chemically distinct lead series. Our primary goal in this work is to demonstrate antiviral efficacy in a murine model of DENV infection, thus laying the foundation for first-in-class direct acting antivirals to treat the growing global threat that DENV poses.",,2025,STANFORD UNIVERSITY,851884,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22439,5R01AI148144-02,Clearance of Blood-Borne Arboviruses,"PROJECT SUMMARY Arboviruses cause serious human disease. Viremia level following arbovirus infection of vertebrates is a critical determinant of viral transmission cycles, global viral spread, and disease severity in individuals. Surprisingly, the factors that dictate viremia following arbovirus infection are poorly defined. We found that multiple arboviruses, including chikungunya (CHIKV), Ross River (RRV), o’nyong nyong (ONNV) and Zika viruses, are cleared from the circulation by phagocytic cells. Experiments in splenectomized mice showed that the spleen is dispensable for arboviral clearance. Instead, virus accumulates in the liver and clearance is independent of natural antibodies and complement factors, suggesting a non-opsonic mechanism. Consistent with this idea, clearance of circulating alphaviruses was blocked by competitive inhibitors of scavenger receptors (SRs) that mediate non- opsonic uptake of non-self and modified-self ligands. Remarkably, we found that single lysine (K) to arginine (R) mutations in the E2 glycoproteins of CHIKV and ONNV (E2 K200R), as well as RRV (E2 K251R), abrogated clearance of circulating alphavirus particles by phagocytic cells, and promoted rapid viral dissemination to distal tissues. Moreover, substitution of CHIKV E2 K200 with a variety of other amino acids also allows for clearance evasion, suggesting a specific interaction between key K residues and a host factor. Ks are targets for post- translational modification (PTM), and mass spectrometry analysis of E2 in virions revealed that CHIKV E2 K200 is ubiquitinated. These experiments have revealed a previously unrecognized pathway that controls arbovirus viremia and dissemination in vertebrates. We hypothesize that PTM of key Ks in viral glycoproteins licenses the capture of circulating arboviruses via SRs expressed on liver Kupffer cells (KCs). In Specific Aim 1, the cell types that capture circulating arboviruses will be defined. We also will determine the role of KCs in viral clearance and dissemination, and the development of anti-viral immunity. Finally, we will evaluate the role of phagocytic cells, and KCs specifically, in the clearance of a genera-spanning panel of arboviruses. In Specific Aim 2, we will define the spectrum of blood-borne arboviruses susceptible to SR-mediated clearance. We will use ELISA and cellular binding assays to determine the murine and human SR(s) that bind virus particles. Using SR knockout mice, we will determine the role of specific SRs in clearance of circulating arboviruses. In Specific Aim 3, we will define the role of E2 ubiquitination in the clearance of circulating CHIKV and RRV. We will use mass spectrometry-based proteomics to determine K residues in arboviral particles that are modified with ubiquitin or other PTMs. Finally, we will use a collection of reverse genetics systems to define the role of specific modified Ks in arboviral clearance from the circulation. This work will provide new mechanistic understanding of arbovirus clearance from the circulation. Elucidating these mechanisms could provide new insight into viral transmission, dissemination, and pathogenesis, identify new risk factors of severe disease, and reveal new therapeutic targets for the treatment of arboviral disease.",,2024,UNIVERSITY OF COLORADO DENVER,465481,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22440,1R01AI153044-01A1,Statistical innovation to integrate sequences and phenotypes for scalable phylodynamic inference,"PROJECT SUMMARY/ABSTRACT This proposal targets the design, development and distribution of Bayesian statistical methods and software to study the historical and real-time emergence of rapidly evolving pathogens, such as Ebola, human immun- odeficiency, inï¬Â'uenza, Lassa, SARS-CoV-2, West Nile, yellow fever and Zika viruses. The proposal exploits novel scalable data integration to equip us for large-scale epidemics and pandemics and help inform action- able public health policy. Our multidisciplinary team carries expertise across statistical thinking, data science, evolutionary biology and infectious diseases to leverage advancing sequencing technology and high-throughput biological experimentation that can characterize 1000s of pathogen genomes, phenotype measurements, eco- logical and clinical information from a single outbreak. Our chief innovations are three-fold. First, we will invent and implement scalable Bayesian phylodynamic techniques to integrate phenotypic measurements and study their correlated evolution with disease spread. Second, we will foster biologically-rich evolutionary models to map and understand heterogeneity in disease evolution through new efficient algorithms. Third, we will develop high-dimensional and mixed-type phenotype models to link concerted viral genotype / phenotype changes using massively parallel computing. Although no competing software exists to integrate phenotype and sequence data at this scale, we will compare restricted cases of our models with reduced datasets to current state-of-the-art approaches to evaluate computational performance improvement and bias that these limitations inject using real- world examples. This proposal will deliver low-level toolbox libraries and user-friendly software for deployment across a rapidly expanding range of large-scale problems in statistics and medicine.",,2025,UNIVERSITY OF CALIFORNIA LOS ANGELES,478330,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Coronavirus | Filoviridae | Flaviviridae | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Lassa fever | COVID-19 | Ebola virus disease | Zika virus disease | Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P22441,7R01AI137472-05,Rational design and evaluation of novel mRNA vaccines against MERS-CoV,"Abstract Traditional strategies of vaccine development suffer from long-term and costly manufacture, and as a result, often fail to respond rapidly to newly emerging and reemerging infectious diseases. By contrast, messenger RNA (mRNA) is rising as a new technology platform to develop vaccines “on demand” against viral pathogens, offering attractive advantages such as cell-free production, non-viral delivery, as well as simple, fast and cost- effective manufacture. Further improvement upon mRNA's stability and translation efficiency, understanding of their immune mechanisms, and evaluation of their protective efficacy will facilitate the development of next- generation mRNA vaccine technologies against diverse viral pathogens. Middle-East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a highly pathogenic, emerging infectious virus posing a continuous threat to public health worldwide. There are currently no MERS vaccines approved for use in humans. MERS-CoV spike (S) protein, particularly its receptor-binding domain (RBD), is an important vaccine target. We have previously shown that MERS-CoV RBD contains a critical neutralizing domain capable of inducing strong cross-neutralizing antibodies and protecting human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice against MERS-CoV infection with outstanding efficacy. However, production of subunit vaccines and other traditional vaccines has limitations, such as low expression and complex purification. To address these unmet challenges, we propose to rationally design and evaluate novel mRNA vaccines, using MERS-CoV as a model pathogen and MERS-CoV S protein as a target antigen. We hypothesize that with appropriate modification and optimization, MERS-CoV S protein RBD-based mRNA vaccines will demonstrate improved stability, increased translation efficiency, and enhanced immunogenicity in both mouse and non-human primates (NHP) models, with protective efficacy on par with the RBD-based subunit vaccine. The specific aims are to (1) rationally design MERS-CoV mRNA vaccines with improved stability and translation efficiency, (2) carefully optimize mRNA formulations and immunization regimens towards in-vivo evaluation of their immunogenicity and mode of action in wild-type mice, and (3) comprehensively evaluate protective efficacy of MERS-CoV mRNA vaccines and elucidate their protective mechanisms in hDPP4-Tg mice and NHPs. Of note, we will also examine the utility of new technologies such as microfluidics and next-generation sequencing (NGS) analysis of B-cell response in mRNA vaccine development and evaluation. The long-term goal is to develop a safe and effective mRNA vaccine that is able to (1) maintain sufficient quantity and quality suitable for industrial- scale production, and (2) meet the WHO Target Product Profiles for rapid onset of immunity in outbreak settings and long-term protection of people at high ongoing risk of MERS-CoV. Together, the proposed project will shed light on protective mechanisms of mRNA vaccines, and provide much-needed information and guidelines for developing mRNA vaccines against diverse viral pathogens with pandemic potential.",,2023,GEORGIA STATE UNIVERSITY,554964,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2021 +P22443,5R21AI149161-02,Transcriptome engineering technologies for the development of antiviral effectors in mosquitoes,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases and there are no drugs or vaccines to treat or prevent the majority of these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. This proposal aims to improve the technologies available to conduct functional analysis of genes in â€Â40 candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be determined over many generations to ensure population stability. The design and integration of these transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression systems, including the impact of transgene expression timing and transgene location on the long-term stability of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies. In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.",,2024,"UNIVERSITY OF CALIFORNIA, SAN DIEGO",460487,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P22531,7R15AI146982-02,"Development of a novel and broadly applicable thermostable bacteriophage VLPs platforms for vaccine design, drug delivery, and imaging","PROJECT SUMMARY Virus-like particles (VLPs) resemble - in size, structure, and immunogenicity - the virus from which the coat or envelope protein(s) are derived from except for the fact they lack a viral genome; VLPs are non-infectious and are safe. These features have been exploited to develop VLP-based vaccines against human papillomaviruses and hepatitis B virus; furthermore, coat proteins from ~70 viruses are currently being explored to develop VLP- based vaccines against these viruses. VLPs from some of these viruses have also been used as display platforms to develop chimeric VLPs displaying heterologous peptides from other infectious agents, tumor- associated antigens and other metabolic diseases. The goal of these chimeric VLPs is to induce antibodies against the heterologous antigen displayed on the platforms and not the platforms. In addition to serving as display platforms, VLPs have also been used for targeted delivery of drugs or cargo to specific cancer cells. While the candidate VLPs-based vaccines displaying heterologous peptides are very effective in animal studies, in the majority of studies, VLPs platforms (including adenoviral VLPs or dodecahedron) are derived from viruses that infect humans and in some cases, studies used VLPs platforms that had previously been used to immunize the general population; a good example is HBV vaccine, with a global infant vaccination coverage of 84% in 2015. Vaccines based on some of these platforms, with pre-existing antibodies in the general population, are likely to be less immunogenic in humans. Additionally, there is a limitation on the size of heterologous antigens that can be genetically displayed on some VLPs platforms making it challenging to display a single peptide with multiple epitopes on the same VLPs. Moreover, most of the VLPs platforms are temperature-sensitive making them less suitable in developing countries with poor refrigeration facilities. In this proposal, the PI will develop and characterize novel thermostable bacteriophage VLPs platforms using coat proteins from thermophilic viruses P23-77 and ΦIN93. P23-77 and ΦIN93 was isolated from bacteria that grow at 70-75 Ã'°C. Thus VLPs derived from these viruses are likely to be stable at room temperature (RT) or above RT. Additional benefit of these VLPs platforms is that because these viruses do not infect humans, the human population lacks pre-existing neutralizing antibodies against the VLPs platforms; thus, the immunogenicity of the platforms cannot be compromised by pre-existing antibodies. Also, many surface- exposed loops on the capsid may tolerate larger insertions of heterologous antigens. The PI will co-express three coat proteins from P23-77 and two coat proteins from ΦIN93. The PI will assess whether the coat proteins can assemble into VLPs, if they VLPs are thermostable, can tolerate heterologous peptide insertions from human papillomaviruses, and if VLPs are immunogenic in comparison to the virus(es).",,2024,TEXAS TECH UNIVERSITY,389276,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P22533,5P41GM132087-02,Functional genomics resources for the Drosophila - TR&D2,"PROJECT SUMMARY â€Â"" TR&D2 Drosophila serves as a model not only of human biology but also of the biology of other dipterans, including mosquito vectors of disease, and provides an instructive example of technologies that can be applied to direct study of other insects. In this project, we focus on development of functional genomics and proteomics resources for the study of mosquito vectors of disease, with a particular focus on development of CRISPR pooled screens for Aedes mosquitoes, which are vectors of viral pathogens including Zika, Dengue, and Chikungunya viruses, and for Anopheles mosquitoes, the vector for malaria. We will additionally develop a pipeline for isolation of robust protein binders, i.e. nanobodies, for use in visualization and in vivo functional blocking, based on a yeast nanobody display platform. A set of collaborators with established assays in mosquitoes will help us to test and improve the screening and nanobody technologies. Altogether, this project will provide much-needed reagents, including a platform for genome-wide screening, for direct study of pathogen entry and other aspects of mosquito biology relevant to infectious diseases and mosquito population control.",,-99,HARVARD MEDICAL SCHOOL,326732,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P22539,1R01AI153064-01,Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses,"ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no effective vaccines are available. Protective immunity against many pathogens can be achieved through long- lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly, our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.) Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced immune mechanisms that regulate the biology of Tfh cells. This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and durable neutralizing antibody responses. This finding could have a significant impact on vaccine development as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable protective antibody responses against many pathogens. We believe that the data generated in this proposal will be capable of moving this vaccine adjuvant towards clinical trials.",,2024,UNIVERSITY OF PENNSYLVANIA,622103,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22540,1R01AI146152-01A1,Validating the Flavivirus Envelope Protein as an Antiviral Target,"PROJECT SUMMARY Dengue virus (DENV) and other flaviviruses are major human pathogens that cause significant disease. Transmitted by widespread mosquito species, many of these viruses spread rapidly and can have a devastating impact on public health where prior immunity does not exist. There is thus a significant need for countermeasures to combat both current and future flavivirus threats. Major limitations in current antivirals development are the relatively small number of validated antiviral targets, most of which are viral enzymes (e.g., polymerases, proteases); the low barrier to resistance when direct-acting antivirals are used as monotherapies; and the narrow spectrum activity of most of these agents (“one bug, one drug”). New classes of targets that can mediate broad-spectrum activity against related viruses and that have high barriers to resistance are particularly needed to combat emerging viruses since we generally lack sufficient time and resources to develop new drugs on a useful time scale once these viruses pose significant threats. Small molecules targeting the flavivirus envelope protein, E, have the potential to mimic the humoral immune response by engaging their target extracellularly and blocking viral entry early in the replication cycle. We have identified multiple small molecule inhibitor series that bind to the DENV envelope protein, E, and inhibit E-mediated membrane fusion during viral entry even when only a minority of copies of E on the particle are inhibitor-bound. These compounds bind in a pocket between domains I and II and inhibit West Nile, Zika, and Japanese encephalitis viruses due to at least partial conservation of this site. We recently established a target-based assay and validated its use in the identification of new inhibitors of DENV and Zika E proteins that bind in the conserved pocket and that have more drug-like properties than our original inhibitors. Building on this work, we now propose a comprehensive plan to rationally optimize small molecule inhibitors of the DENV E protein as a potential anti-viral strategy. Towards this end, we will combine modeling and structure- guided drug design with an efficient screening cascade using complementary target-based biochemical, cellular and mechanistic assays to enable efficient optimization of two chemically distinct lead series. Our primary goal in this work is to demonstrate antiviral efficacy in a murine model of DENV infection, thus laying the foundation for first-in-class direct acting antivirals to treat the growing global threat that DENV poses.",,2025,HARVARD MEDICAL SCHOOL,833361,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22542,1R01AI148144-01,Clearance of Blood-Borne Arboviruses,"PROJECT SUMMARY Arboviruses cause serious human disease. Viremia level following arbovirus infection of vertebrates is a critical determinant of viral transmission cycles, global viral spread, and disease severity in individuals. Surprisingly, the factors that dictate viremia following arbovirus infection are poorly defined. We found that multiple arboviruses, including chikungunya (CHIKV), Ross River (RRV), o’nyong nyong (ONNV) and Zika viruses, are cleared from the circulation by phagocytic cells. Experiments in splenectomized mice showed that the spleen is dispensable for arboviral clearance. Instead, virus accumulates in the liver and clearance is independent of natural antibodies and complement factors, suggesting a non-opsonic mechanism. Consistent with this idea, clearance of circulating alphaviruses was blocked by competitive inhibitors of scavenger receptors (SRs) that mediate non- opsonic uptake of non-self and modified-self ligands. Remarkably, we found that single lysine (K) to arginine (R) mutations in the E2 glycoproteins of CHIKV and ONNV (E2 K200R), as well as RRV (E2 K251R), abrogated clearance of circulating alphavirus particles by phagocytic cells, and promoted rapid viral dissemination to distal tissues. Moreover, substitution of CHIKV E2 K200 with a variety of other amino acids also allows for clearance evasion, suggesting a specific interaction between key K residues and a host factor. Ks are targets for post- translational modification (PTM), and mass spectrometry analysis of E2 in virions revealed that CHIKV E2 K200 is ubiquitinated. These experiments have revealed a previously unrecognized pathway that controls arbovirus viremia and dissemination in vertebrates. We hypothesize that PTM of key Ks in viral glycoproteins licenses the capture of circulating arboviruses via SRs expressed on liver Kupffer cells (KCs). In Specific Aim 1, the cell types that capture circulating arboviruses will be defined. We also will determine the role of KCs in viral clearance and dissemination, and the development of anti-viral immunity. Finally, we will evaluate the role of phagocytic cells, and KCs specifically, in the clearance of a genera-spanning panel of arboviruses. In Specific Aim 2, we will define the spectrum of blood-borne arboviruses susceptible to SR-mediated clearance. We will use ELISA and cellular binding assays to determine the murine and human SR(s) that bind virus particles. Using SR knockout mice, we will determine the role of specific SRs in clearance of circulating arboviruses. In Specific Aim 3, we will define the role of E2 ubiquitination in the clearance of circulating CHIKV and RRV. We will use mass spectrometry-based proteomics to determine K residues in arboviral particles that are modified with ubiquitin or other PTMs. Finally, we will use a collection of reverse genetics systems to define the role of specific modified Ks in arboviral clearance from the circulation. This work will provide new mechanistic understanding of arbovirus clearance from the circulation. Elucidating these mechanisms could provide new insight into viral transmission, dissemination, and pathogenesis, identify new risk factors of severe disease, and reveal new therapeutic targets for the treatment of arboviral disease.",,2024,UNIVERSITY OF COLORADO DENVER,465481,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Bunyaviridae | Unspecified,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22544,1R21AI149161-01,Transcriptome engineering technologies for the development of antiviral effectors in mosquitoes,"PROJECT SUMMARY Billions of people are at risk of contracting vector-borne diseases and there are no drugs or vaccines to treat or prevent the majority of these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. This proposal aims to improve the technologies available to conduct functional analysis of genes in â€Â30 million deaths worldwide within 6 months. Current vaccines generate an antibody immune re- sponse against surface proteins, which change constantly, requiring annual updates. Moreover, their effective- ness may be as low as 10-20% when circulating viruses do not match the vaccine viruses. As seasonal influenza vaccines are highly strain-specific, they would provide very limited protection against novel pandemic strains. The best way to prevent an unknown future seasonal or pandemic influenza strain is with a vaccine with efficacy against as broad a range of strains as possible â€Â"" preferably universal efficacy. To do so, it must target an antigen that is highly conserved among all influenza strains and subtypes. Nucleoprotein (NP) is very well conserved within A-strains (up to 95%). NP-specific T-cells present in patients before exposure correlate with >70% reduc- tion in influenza A â€Â"" both pandemic and seasonal. Therefore, we hypothesize that T-cell immunization against NP would have broad-spectrum (possibly universal) efficacy against influenza, including pandemic strains. Osivax is proposing a novel approach based on its proprietary platform technology, oligoDOMÃ'®, to generate heptameric antigens with improved humoral and cellular immunogenicity. Using this technology, Osivax devel- oped OVX836: a recombinant protein in which the full-length NP sequence of an H1N1 influenza strain was fused to oligoDOMÃ'®. OVX836 generates high, long-lasting, and dose-dependent humoral and T-cell responses in mice, leading to cross-protective efficacy against lethal challenge by both homologous and heterologous in- fluenza A- and B-strains. This efficacy was confirmed clinically in two Phase 2a clinical trials conducted during influenza seasons in which heterologous H1N1 and H3N2 strains were dominant, with efficacy in the range of 75-80%, in line with the WHO/NIAID aspirational efficacy target for influenza vaccines. The main advantage of OVX836 over other vaccines is that it is universal, multi-season and strain-independent. Moreover, it stimulates all three arms of immunity â€Â"" CD8+ T-cells, CD4+ T-cells and antibodies â€Â"" in contrast to existing vaccines, which rely mostly on an antibody response against surface antigens that are highly prone to mutations. This project aims to demonstrate the breadth of protection conferred by OVX836 against two heterologous influ- enza A-strains â€Â"" namely the once pandemic but now seasonal pH1N1 (Specific Aim #1) and H5N1, a highly pathogenic strain with pandemic potential (Specific Aim #2) â€Â"" in a non-human primate (NHP) challenge model. While a naïve infection model is simpler and more convenient, a pre-infected model is likely to better mimic the human condition. Therefore, in order to validate a pre-infection model, we propose to evaluate the protection and immune response conferred by OVX836 in naïve and pre-infected NHPs. By evaluating the immune re- sponses in NHPs we will also further investigate the mechanism of action of our vaccine and identify potential correlates of protection to be further evaluated in human.",,2026,OSIVAX SAS,529857,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Europe,,Innovation,,,France,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity",2023 +P22674,5R01AI154656-03,Seasonal and universal Vaccination in aged populations with pre-existing immunity,"PROJECT SUMMARY Current influenza (flu) vaccination based on hypervariable hemagglutinin (HA) protein fails to provide effective cross protection. The efficacy of vaccination is low in the aged populations even with pre-existing immunity. The impacts of pre-existing immunity on the immunogenicity and efficacy of universal and seasonal vaccination largely remain not well understood in the aged populations. Development of new flu vaccines and vaccination strategies improving cross protective efficacy in young naïve and aged hosts with pre-existing immunity is of high priority. Mono conserved antigenic targets inducing cross protection tested in naïve animal models include the flu A virus M2 extracellular domain (M2e), HA-stalk domains, and neuraminidase (NA) were reported but insufficient for translation to humans. The multi-target universal vaccines in naïve and aged hosts with pre-existing immunity remain to be developed. We developed heterologous tandem repeat of M2e (5xM2e) presented on immunogenic virus-like particles (5xM2e VLP). Vaccination with 5xM2e VLP was effective in broadening cross protection but suboptimal. A further improved universal vaccine should be developed. Our preliminary studies found synergistic effects on improving cross protection by both M2e and NA immunity. Therefore, as a new universal vaccine candidate, we developed a multi NA + 5xM2e VLP vaccine containing multi-subtype NA and 5xM2e on the same VLP particle. In addition, we newly designed genetically linked novel recombinant M2e-stalk universal protein vaccines effectively inducing both M2e and HA-stalk immunity and conferring broad cross- group protection. Adjuvanted universal vaccination will overcome the aging-related immune senescence by activating T and B immune cells in naïve hosts or aged populations under pre-existing immunity. In this project, we will test the hypothesis that new universal vaccination inducing multi immunity (M2e, Stalk, NA) will enhance the breadth and efficacy of cross protection in adult and aged populations with or without pre-existing immunity. Under Aim 1, we will determine the efficacy of multi-target universal vaccines in young adult mice and ferrets under naïve and pre-existing immune conditions. In Aim 2 studies, we will determine the durability of cross protective immunity by multi targeting new universal vaccines and test a vaccination strategy enhancing cross protection in aged mouse and ferret animal models. In the Aim 3, we will investigate cross protective immune mechanisms of multi targeting universal vaccination in young and aged mouse models. The outcomes in this project will be highly significant in the aspect of translational science and relevance to improve the cross protective efficacy of flu vaccination.",,2026,Georgia State University,542726,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P22676,5R01AI167910-02,Sequence-function relationship of influenza broadly neutralizing antibodies,"PROJECT SUMMARY Influenza A virus continues to be a major global health concern due to antigenic drifts and shifts. Rapid antigenic drifts of circulating human influenza subtypes (H1N1 and H3N2), which are caused by point mutations, can drastically hamper vaccine effectiveness despite annual update of the seasonal influenza vaccine. On the other hand, antigenic shifts, which are caused by genetic reassortment between antigenically distinct strains, can result in devastating pandemic as exemplified by the 1918 Spanish flu. Human infections with different zoonotic subtypes, such as H5N1, H6N1, H7N9, H9N2, and H10N8 have also been reported. As a result, a universal influenza vaccine that can elicit broadly protective antibody responses to diverse influenza strains and subtypes is urgently needed. The discovery of broadly neutralizing antibodies (bnAbs) that target the conserved stem region of influenza hemagglutinin (HA) has raised the possibility of developing a universal influenza vaccine. A number of HA stem bnAbs are encoded by immunoglobulin heavy chain germline gene IGHV6-1. Since these IGHV6-1 HA stem bnAbs can be found in multiple individuals and can cross-react with both group 1 HAs (H1, H2, H5, H6, H8, H9, H11, H12, H13, and H16) and group 2 HAs (H3, H4, H7, H10, H14, and H15), they represent the type of antibody response that needs to be induced by a universal influenza vaccine. This proposed study will use innovative high-throughput experiments to define sequence features in the heavy-chain complementarity-determining region 3, light chain, and somatic hypermutations, that enable an IGHV6-1 antibody to be a cross-group HA stem bnAbs. The underlying molecular mechanisms will be further characterized by structural biology approach. The results will help accurately estimate the germline frequency of IGHV6-1 HA stem bnAbs and understand their affinity maturation pathway, which in turn will benefit the design of a universal influenza vaccine. Furthermore, the experimental framework established in this study will be applicable to characterize any antibody of interest.",,2026,UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN,459505,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2022 +P22678,3R01AI167910-02S1,Sequence-function relationship of influenza broadly neutralizing antibodies,"PROJECT SUMMARY Influenza A virus continues to be a major global health concern due to antigenic drifts and shifts. Rapid antigenic drifts of circulating human influenza subtypes (H1N1 and H3N2), which are caused by point mutations, can drastically hamper vaccine effectiveness despite annual update of the seasonal influenza vaccine. On the other hand, antigenic shifts, which are caused by genetic reassortment between antigenically distinct strains, can result in devastating pandemic as exemplified by the 1918 Spanish flu. Human infections with different zoonotic subtypes, such as H5N1, H6N1, H7N9, H9N2, and H10N8 have also been reported. As a result, a universal influenza vaccine that can elicit broadly protective antibody responses to diverse influenza strains and subtypes is urgently needed. The discovery of broadly neutralizing antibodies (bnAbs) that target the conserved stem region of influenza hemagglutinin (HA) has raised the possibility of developing a universal influenza vaccine. A number of HA stem bnAbs are encoded by immunoglobulin heavy chain germline gene IGHV6-1. Since these IGHV6-1 HA stem bnAbs can be found in multiple individuals and can cross-react with both group 1 HAs (H1, H2, H5, H6, H8, H9, H11, H12, H13, and H16) and group 2 HAs (H3, H4, H7, H10, H14, and H15), they represent the type of antibody response that needs to be induced by a universal influenza vaccine. This proposed study will use innovative high-throughput experiments to define sequence features in the heavy-chain complementarity-determining region 3, light chain, and somatic hypermutations, that enable an IGHV6-1 antibody to be a cross-group HA stem bnAbs. The underlying molecular mechanisms will be further characterized by structural biology approach. The results will help accurately estimate the germline frequency of IGHV6-1 HA stem bnAbs and understand their affinity maturation pathway, which in turn will benefit the design of a universal influenza vaccine. Furthermore, the experimental framework established in this study will be applicable to characterize any antibody of interest.",,2026,UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN,36248,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2022 +P22679,1R15HD109732-01A1,New Nasal Spray Influenza Vaccine for Children,"New Nasal Spray Influenza Vaccine for Children Project Summary Influenza is still a global public health problem for children despite a vigorous campaign for influenza vaccination in many countries. Recent emergence of the COVID-19 can also complicate influenza in children and make it more desirable to vaccinate young children against influenza. Influenza vaccines must be reformulated annually because of the antigenic shift and drift of circulating influenza viral strains. However, reformulated seasonal flu vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt for transmission in humans. Additionally, currently available antiviral drugs against influenza are facing the twin challenges of evolved drug resistance and nonspecific side effects. Therefore, there is an urgent need for developing novel drugs, vaccines, and combinatory therapies against influenza virus infection. In this proposed research, we hypothesize that a universally prophylactic and therapeutic influenza vaccine for children can be developed through creation of a self-attenuated influenza virus (SAIV) that expresses artificial microRNAs (amiRNAs) targeting viral and/or host gene expression that are essential for viral replication. In order to evaluate this hypothesis, we propose the following 3 specific aims for this research: Specific Aim 1: To evaluate the efficacy of a candidate prophylactic and therapeutic SAIV vaccine generated by viral gene-targeted attenuation. Specific Aim 2: To assess the efficacy of a candidate SAIV vaccine generated by host gene-targeted attenuation. Specific Aim 3: To produce and evaluate additional dual viral and host factor-targeted prophylactic and therapeutic SAIV vaccines. Our proposed SAIV vaccines developed in this research will be extensively investigated in young mouse model of influenza infection. We anticipate that the proposed research will identify a novel and safe universal influenza vaccine and molecular therapy that could be further developed as a therapeutic vaccine to prevent future influenza reinfection in children. Furthermore, this research program will significantly strengthen the research environment in Texas Tech University Health Sciences Center at El Paso, and provide research training opportunities for 3 graduate students, 3 medical students, and 3 undergraduate students, respectively, throughout the 3-year performance period.",,2026,TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER AT EL PASO,480000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P22681,4R44AI157074-02,"Preclinical development of an important, broad-spectrum antibody for pandemic influenza","Health and human services (HHS) and the Biomedical Advanced Research and Development Authority (BARDA) have suggested a severe pandemic influenza outbreak is the greatest current threat to national and global security. The Center for Disease Control rates H7N9 as the most threatening of the Influenza A viruses as it, along with H5N1, have fatality rates of ~40% and ~60%, respectively. Models have predicted that an H7N9 pandemic could result in infection of one third of the world population and death of ~40% of those infected, making it the deadliest virus in recorded history (the 1918 flu had a fatality rate of ~2.5%). There is currently no approved therapeutic for severe influenza infection, and in the case of H7N9 ~98% of those infected develop severe infection and require hospitalization. This project seeks to provide some hope of protection in such an outbreak by advancing the most effective broad-spectrum human antibody therapeutic currently available, CM-IAV1. CM-IAV1 has great promise since it has already been shown to protect mice against lethal (non-laboratory strain) H7N9 and H5N1 when given in a single dose 72 hours post-infection. We have assembled a world-class team with outstanding preclinical data and are now focused on advancing CM-IAV1 into the clinic. The experiments presented in this application will take a promising laboratory product and, together with our continued and parallel investments, create a clinical asset with enormous potential to reduce morbidity and mortality associated influenza infection from the most relevant CDC- prioritized pandemic strains. We believe that development of this antibody, at this time, and by this team represents the best hope of offering meaningful lifesaving protection against the terrifying possibility of a global Influenza A outbreak. The overarching goal of this project is to advance a novel broad-spectrum, lifesaving therapeutic for pandemic influenza A infection from promising preclinical candidate through investigational new drug (IND)-enabling studies to IND filing. ",,2025,"CELDARA MEDICAL, LLC",999635,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | H7,,,,H5N1,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P22682,2R44AI167158-02,Rapid response to pandemic influenza via multi-antigen RNA-based vaccine,"Project Abstract Avian influenza A H7N9 causes severe respiratory illness with a high mortality rate, and its zoonotic capacity has raised serious concerns over the possibility of a pandemic. The value of vaccines for pandemic-potential viruses has been demonstrated by the devastating effects of COVID-19 on human health and the economy. Development of H7 Influenza vaccines has lagged, as pandemic influenza vaccines have generally been developed with traditional technologies, and low immunogenicity for H7 products in humans has been reported. The high threat presented by this strain represents a substantial market gap for newer technologies to fill. The COVID-19 pandemic illustrated the potential of RNA vaccines as a rapid-response platform, but also demonstrated their limitations. Current generation vaccines relying on lipid nanoparticle (LNP) delivery are known to elicit unwanted acute inflammatory responses and require ultra-low temperatures for long-term storage and stable refrigeration at the point-of-care, highlighting the need for new delivery approaches. In Phase I studies, Tiba Biotech established Proof-of-Principle that an intramuscular immunization of BALB/cJ mice with a novel, less inflammatory formulation containing a proprietary delivery molecule and highly immunogenic RNA replicons encoding the H7N9 hemagglutinin (HA), Neuraminidase (NA) and Nucleoprotein (NP) at a 1:1:1 mass ratio induced immune responses against all antigens. This approach is expected to increase the immunogenicity and heterotypic protective potential of the vaccine, and the RNABL platform that is utilized maximizes the safely delivered RNA mass content, protects RNA from degradation, and enables efficient uptake by cells in vivo. In Phase II, Tiba Biotech plans to further develop the prototype H7N9 vaccine by evaluating different ratios of RNAs and delivery materials from Tiba’s enhanced RNABL library, developing manufacturing, scale up and quality control processes for the RNA components of the vaccine, determining optimal dosing in a mouse model, establishing protective efficacy in a highly relevant ferret challenge model, and performing preliminary safety assessments and biodistribution studies in rats. These studies will enable a request for a pre-IND meeting, and this meeting will be used to inform further experiments prior to IND filing and clinical trials. Ultimately, this vaccine product will have the potential for commercialization and use in vaccine stockpiling, enabling preparedness in the case of a H7N9 influenza pandemic. In addition, the prototype composition developed here will serve as a platform into which any outbreak antigen sequences could be rapidly implemented.",,2026,"TIBA BIOTECH, LLC",966637,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H7,,,,,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P22683,1R01AI162670-01A1,Yersinia Outer-Membrane-Vesicle Vaccines Against Pneumonic Plague,"SUMMARY Yersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. Plague has been classified as a re-emerging disease by the World Health Organization since there are several thousand reported cases of the disease worldwide annually and multidrug-resistant Y. pestis strains occur in recent years. The plague bacillus has been used as a biological weapon recorded in human history and is one of the more likely biological threats to be used by terrorists. Currently, no licensed plague vaccines are available in Western world. Isolation of virulent F1-negative Y. pestis strains from natural sources and the existence of lcrV polymorphisms in Yersinia may result in Y. pestis variants that escape protective immunity induced by LcrV and F1 antigens. Therefore, vaccines solely based upon LcrV and F1 antigens is insufficient to guarantee long-term defense against plague in humans. In order to overcome the drawbacks of subunit vaccines composed of LcrV and F1 antigens, we propose to use Y. pseudotuberculosis (Yptb) OMVs as an acellular vaccine against plague: (1) Construct Yptb strains which robustly produce highly immunogenic self-adjuvanting OMVs carrying an array of Y. pestis protective antigens; (2) Evaluate protective immunity of OMVs in rodents (mouse and rat). (3) Carefully decipher mechanisms of immune protection induced by the Yersinia OMVs to provide fundamentals for rational plague vaccine development. Finally, the success of this project will provide highly effective and safe plague vaccines for humans.",,2026,ALBANY MEDICAL COLLEGE,584647,Animals | Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration,2022 +P22684,3R01AI162670-01A1S1,Yersinia Outer-Membrane-Vesicle Vaccines Against Pneumonic Plague,"SUMMARY Yersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. Plague has been classified as a re-emerging disease by the World Health Organization since there are several thousand reported cases of the disease worldwide annually and multidrug-resistant Y. pestis strains occur in recent years. The plague bacillus has been used as a biological weapon recorded in human history and is one of the more likely biological threats to be used by terrorists. Currently, no licensed plague vaccines are available in Western world. Isolation of virulent F1-negative Y. pestis strains from natural sources and the existence of lcrV polymorphisms in Yersinia may result in Y. pestis variants that escape protective immunity induced by LcrV and F1 antigens. Therefore, vaccines solely based upon LcrV and F1 antigens is insufficient to guarantee long-term defense against plague in humans. In order to overcome the drawbacks of subunit vaccines composed of LcrV and F1 antigens, we propose to use Y. pseudotuberculosis (Yptb) OMVs as an acellular vaccine against plague: (1) Construct Yptb strains which robustly produce highly immunogenic self-adjuvanting OMVs carrying an array of Y. pestis protective antigens; (2) Evaluate protective immunity of OMVs in rodents (mouse and rat). (3) Carefully decipher mechanisms of immune protection induced by the Yersinia OMVs to provide fundamentals for rational plague vaccine development. Finally, the success of this project will provide highly effective and safe plague vaccines for humans.",,2026,ALBANY MEDICAL COLLEGE,254100,Animals | Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration,2022 +P22685,5R03AI155950-02,Inflammation and the Treatment of Primary Pneumonic Plague,"Project Summary Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Disease manifests as a rapidly progressing and highly lethal necrotic pneumonia that is typically fatal within seven days. If antibiotic treatment is not administered within 24 hours after the onset of symptoms, pneumonic plague is 100% fatal. Even in the event of appropriate antibiotic therapy, as evidenced in recent outbreaks mortality can still approach 50%. The rapid progression of pneumonic plague and its difficulty to treat highlight a need for improved therapeutic options and a more complete understanding of the host factors driving disease progression. The work proposed here seeks to evaluate the suppression of damaging host immune responses coupled with antibiotic therapy to treat late-stage pneumonic plague. Further, host responses and physiological parameters in the lung are monitored during disease and treatment to understand those conditions that correlate with survival, and those that accompany lethality. The ultimate goals of the proposal are to identify conditions for treatment of late-stage pneumonic plague that favor survivability. This work may have lasting impact on pneumonic plague treatment, as well as severe pneumonia caused by a number of pathogens. The specific aims of the proposal are as follows: Aim 1. Co-treatment with antibiotics and corticosteroids for late-stage pneumonic plague. Preliminary data indicates that pretreating mice with the corticosteroid fluticasone propionate dramatically increases survival after antibiotic treatment of pneumonic plague. Aim 1 seeks to test co-administration of different classes of antibiotics and corticosteroids to treat late-stage pneumonic plague, which is difficult to treat and is highly fatal. This is the first study of its kind that focuses on treatment of disease after symptoms arise. The goal of Aim 1 is to develop an optimal treatment regime for severe and lethal pneumonic plague. Aim 2. Evaluate pulmonary function and innate immune responses during treatment of pneumonic plague. The finding that limiting pulmonary inflammation increases survival in mice offers the opportunity to evaluate host responses under conditions associated with both survivability and lethality. Aim 2 seeks to evaluate host inflammatory responses, immune cell repertoire, and physiological conditions in the lung during disease and treatment of pneumonic plague to identify those conditions that lead to lethality. Further, identifying pulmonary conditions conducive to survival may help to define key metrics and goals for the development of effective therapeutics.",,2023,UNIV OF ARKANSAS FOR MED SCIS,76000,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22686,5R01AI153252-02,Defining the Role of the Plasminogen Activator Protease in the Early Events that Establish Primary Pneumonic Plague,"Project Summary Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Early after infection, Y. pestis subverts host innate immune mechanisms in the lung and replicates to high numbers before the onset of lethal host inflammatory responses. As a result, pneumonic plague is difficult to treat once symptoms are recognized. This proposal introduces the Yersinia Plasminogen activator protease (Pla) as an important mediator of early host/pathogen interactions in the lung. Pla is well-established virulence factor known to be essential to the pathogenesis of pneumonic plague via an unknown function. The work proposed here examines the dual role of Pla, as both an adhesin and a protease, during pulmonary infection. The objective of this work is to define the function of the critical Yersinia virulence factor Pla in the early events of pneumonic plague to understand how Y. pestis resists clearance by host inflammatory responses to establish an initial replicative phase in the lungs. The strategy for this proposal is outlined below: Specific Aim 1. Define the role of Pla-mediated T3S during pneumonic plague. The adhesin function of Pla facilitates targeting of alveolar macrophages for type 3 secretion (T3S) early during pneumonic plague. Aim 1 will generate and test mutants of Pla to understand how Pla mediates adherence, and characterize the importance of Pla-mediated adherence and T3S in vivo. Further, the impact of Pla-mediated T3S on host cell innate immune responses to T3S will be evaluated during infection to understand how Y. pestis limits host responsiveness early during infection. Specific Aim 2. Characterize novel proteolytic functions of Pla during pneumonic plague. Preliminary data has identified two novel functions of Pla that may contribute to pathogenesis. A proteomics approach will be used to identify and characterize Pla proteolytic activity early during primary pneumonic plague. Specific Aim 3. Identify key host cell types and dynamics responsible for establishing an early pre- inflammatory disease phase during pneumonic plague. Preliminary data indicates that deletion of Pla disrupts the ability of Y. pestis to limit early innate immune responses in the lung. In Aim 3 we will evaluate host cell dynamics and innate immune responses in the lung in the presence and absence of Pla to understand how Y. pestis is able to subvert initial inflammatory responses and establish infection in the lung.",,2026,UNIV OF ARKANSAS FOR MED SCIS,374355,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +P22687,5F32GM140568-02,Characterizing variation and adaptation in the immune response to plague (Y. pestis) through single-cell sequencing and ancient genomics,"PROJECT SUMMARY Pathogens have been one of the strongest selective pressures in human evolution. Migrating out of Africa, modern humans encountered novel pathogens along with new environments. These populations likely adapted to these pathogens, leading to population-specific adaptations. Consistent with this hypothesis, some of the most compelling signatures of local adaptation in the human genome overlap genes involved in immunity and host defense. Importantly, these regions also overlap genetic loci which are associated with infectious, autoimmune, and inflammatory disease risk in modern humans. Thus, understanding adaptation to pathogens throughout history is important for understanding modern human health. The Black Plague was likely one of the strongest selective events in recent human history. Exposure to Yersinia pestis (the causative agent of plague) therefore likely drove adaptations in the human immune system which continue to shape modern immune variation. Importantly, because the plague ravaged Eurasia while leaving sub-Saharan Africa relatively untouched, adaptation to plague likely occurred in European but not African populations. However, it is not known whether human populations differ in their immune response to plague as a consequence of prior evolutionary history. Addressing this gap is not only important for understanding the recent evolution of the human immune system, but may also help reveal the molecular basis of ancestry-related differences in susceptibility to infectious disease, chronic inflammation, and autoimmune disorders. The basic research questions driving this proposal are: What was the impact of Y. pestis to the functional differentiation of immune responses between African- and European-ancestry individuals? To which extent natural selection has favored the increase in frequency of protective alleles in Europeans, a population with increased exposure to Y. pestis? What cell types and immunological pathways show the most divergence in response to Y. pestis between populations? To answer this questions, I will experimentally infected peripheral blood cells in culture to characterize the immune response to plague. Using single-cell RNA sequencing I will be able to analyze variation in the immune response across cell types, but also characterize differences in the proportion of cells responding to infection and the strength of that response. Using this data, I will identify genes and pathways which are regulated differently in individuals of European and African ancestry, and identify genetic variants which contribute to these differences. I will then use a combination of ancient and modern genomics to test whether loci underlying variation in the immune response to Y. pestis also experienced position selection during the Black Plague. Thus, this project is a novel integration of functional and population genetic approaches to study adaptation to a deadly human pathogen. At its conclusion, this study will reveal how Europeans adapted to Y. pestis exposure during the plague, and identify highly-promising genetic candidates which may contribute to disease susceptibility in modern human populations.",,2024,University Of Chicago,67582,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +P22688,5F31AI147404-03,Identification of a novel zinc acquisition system in Yersinia pestis,"PROJECT SUMMARY Yersinia pestis is the causative agent of human plague. Every year, approximately 2,000 cases of human plague occur, and in the past, several pandemics of plague have caused wide spread population loss. Y. pestis poses a threat to modern society due to its potential to be used as a bioterrorism agent, the absence of a FDA approved vaccine, and the possibility of antibiotic resistance. The identification of novel targets for therapeutic agents is critical for public health and safety. Consequently, Y. pestis is considered a Tier 1 Select Agent. For survival and virulence, Y. pestis must acquire transition metals, such as Fe, Zn, and Mn and overcome nutritional immunity, mechanisms in eukaryotic organisms that restrict nutrients from invading bacteria. During human plague, Yersinia pestis is able to overcome Fe limitation via production of the siderophore Yersiniabactin (Ybt). Recently, we identified an unexpected role for the Ybt system in the ability of Y. pestis to acquire Zn during infection. While the ZnuABC system contributes to in vitro growth in Zn-deficient media, a znu mutant is not attenuated in the mouse model of plague, unless the mutant also lacks genes involved in Ybt synthesis. These data suggest that Y. pestis uses two redundant Zn acquisition systems to cause plague. We hypothesize that Y. pestis produces a novel Ybt synthetase-dependent zincophore required for zinc acquisition and virulence. In Specific Aim 1, we will use a novel Tn-seq method to define genetic elements involved in the zincophore system. Genes that show a Zn phenotype will be validated through growth assays, trans-complementation, and biochemical experiments. In Specific Aim 2, we will determine the contribution of the Ybt synthetase-dependent zinc acquisition system to virulence by utilizing a hemochromatosis mouse model. The hemochromatosis mouse is defective in Fe nutritional immunity, which will allow us to distinguish between the contributions of Ybt synthetase-dependent Fe acquisition and Ybt synthetase-dependent Zn acquisition to Y. pestis virulence. In Specific Aim 3, we will determine the impact of calprotectin on Y. pestis virulence by using in vitro and in vivo methods. Completion of these Aims will define a novel secreted Zn acquisition system in Y. pestis. Our studies will be the first to determine the contribution of Zn acquisition to Y. pestis virulence in the mammalian host and the effect of calprotectin on plague infection. Furthermore, the involvement of conserved Ybt in this novel Zn acquisition demonstrates the significance of these studies to other bacterial pathogens.",,2022,UNIVERSITY OF LOUISVILLE,33353,Animals | Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies",2020 +P22689,3R01AI148241-02S1,Iron independent role for yersiniabactin in Yersinia pestis,"SUMMARY Transitional metals (e.g., Fe, Zn, Mn) are required by bacteria in order to grow. As such, mammals have a variety of mechanisms to sequester these metals during infection, effectively limiting their availability for use by bacteria (referred to as nutritional immunity). Yersinia pestis, which causes the human disease plague, needed to evolve high-affinity metal acquisition mechanisms to overcome nutritional immunity and colonize its hosts. Because these mechanisms are key to Y. pestis virulence, they represent potential therapeutic targets for the treatment or prevention of plague. Therefore, our long term goals are to identify the mechanisms used by Y. pestis to evade host nutritional immunity and define their roles in virulence. Recently, we have made the exciting discovery that yersiniabactin (Ybt), a siderophore essential for Y. pestis iron (Fe) acquisition, is also able to bind to zinc (Zn), and contributes to Zn acquisition in vitro. Furthermore, using a hemochromatosis mouse model that is defective in Fe-mediated nutritional immunity, we demonstrated for the first time that Ybt contributes to virulence in an Fe-independent manner. Using a Y. pestis mutant defective in Zn acquisition, was also showed that the host protein calprotectin, which is a key component to Zn-mediated nutritional immunity, is a barrier to Y. pestis infection, and Ybt contributes to overcoming this barrier in both pneumonic and bubonic plague. Together, these data are our premise for the conceptually innovative hypothesis that Ybt not only contributes to virulence through Fe acquisition, but also contributes to Zn acquisition, which aids in overcoming calprotectin mediated nutritional immunity. In this proposal, we will build on these exciting discoveries. In Aim 1, we will define the mechanisms that govern metal selectivity of Ybt and the re-acquisition of Ybt-Zn by the bacterium. In Aim 2, we will define the Ybt secretion mechanisms used by Y. pestis and determine the therapeutic potential of inhibiting these secretion systems during plague. Finally, in Aim 3, we will define the role of host calprotectin during plague and the contribution of Ybt to the ability of Y. pestis in overcoming calprotectin mediated Zn sequestration. Importantly, Ybt is a conserved virulence factor in many Gram-negative bacteria. Therefore, the data generated from these studies has the potential to provide us with a broader understanding of the role of Ybt in the virulence of multiple pathogens. Ultimately, these data will provide a foundation for the rational design of new therapeutic approaches targeting these mechanisms to combat Y. pestis infection.",,2026,University Of Louisville,355032,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22690,5R01AI148241-02,Iron independent role for yersiniabactin in Yersinia pestis,"SUMMARY Transitional metals (e.g., Fe, Zn, Mn) are required by bacteria in order to grow. As such, mammals have a variety of mechanisms to sequester these metals during infection, effectively limiting their availability for use by bacteria (referred to as nutritional immunity). Yersinia pestis, which causes the human disease plague, needed to evolve high-affinity metal acquisition mechanisms to overcome nutritional immunity and colonize its hosts. Because these mechanisms are key to Y. pestis virulence, they represent potential therapeutic targets for the treatment or prevention of plague. Therefore, our long term goals are to identify the mechanisms used by Y. pestis to evade host nutritional immunity and define their roles in virulence. Recently, we have made the exciting discovery that yersiniabactin (Ybt), a siderophore essential for Y. pestis iron (Fe) acquisition, is also able to bind to zinc (Zn), and contributes to Zn acquisition in vitro. Furthermore, using a hemochromatosis mouse model that is defective in Fe-mediated nutritional immunity, we demonstrated for the first time that Ybt contributes to virulence in an Fe-independent manner. Using a Y. pestis mutant defective in Zn acquisition, was also showed that the host protein calprotectin, which is a key component to Zn-mediated nutritional immunity, is a barrier to Y. pestis infection, and Ybt contributes to overcoming this barrier in both pneumonic and bubonic plague. Together, these data are our premise for the conceptually innovative hypothesis that Ybt not only contributes to virulence through Fe acquisition, but also contributes to Zn acquisition, which aids in overcoming calprotectin mediated nutritional immunity. In this proposal, we will build on these exciting discoveries. In Aim 1, we will define the mechanisms that govern metal selectivity of Ybt and the re-acquisition of Ybt-Zn by the bacterium. In Aim 2, we will define the Ybt secretion mechanisms used by Y. pestis and determine the therapeutic potential of inhibiting these secretion systems during plague. Finally, in Aim 3, we will define the role of host calprotectin during plague and the contribution of Ybt to the ability of Y. pestis in overcoming calprotectin mediated Zn sequestration. Importantly, Ybt is a conserved virulence factor in many Gram-negative bacteria. Therefore, the data generated from these studies has the potential to provide us with a broader understanding of the role of Ybt in the virulence of multiple pathogens. Ultimately, these data will provide a foundation for the rational design of new therapeutic approaches targeting these mechanisms to combat Y. pestis infection.",,2026,University Of Louisville,546234,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22691,5R35GM142939-02,Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA,"PROJECT SUMMARY The possibility of recovering ancient DNA (aDNA) molecules from archeological samples has yielded great opportunities for the study of human evolution and history. Compared to traditional datasets composed of a single time point collected in the present, aDNA allows for the detection of lost genetic lineages and enables the direct assessment of allele frequencies in different time transects. Technologies for obtaining genomic data from archeological material have catapulted the development of the field of paleogenomics, but statistical methods to leverage information from time-series genetic datasets lag behind these technological advances. Over the next five years, the Amorim Lab will develop and apply methods to study human host-pathogen coevolution and adaptation using aDNA. We seek to advance the field of paleogenomics by generating aDNA datasets that comprise large sample sizes per archeological site and developing new methods and approaches to leverage information from time-series genetic data. We will use these novel resources to study host-pathogen interactions during the outbreaks of the plague in Eurasia (e.g. the Black Death) and the period of contact between Indigenous peoples from South America and European colonizers. Contrasting models of population evolution, both analytical and computational, with observed allele frequencies and other summary statistics in different time transects, we will identify the genetic signatures of host-pathogen interactions, characterize the evolutionary processes involved in human response to pathogens, and infer the strength and timing of selective sweeps. In addition, we will characterize the Distribution of Fitness Effects (DFE) of new mutations in the human genome across different time transects and analyze its evolution in light of the environmental shifts caused by disease outbreaks and other events. This study represents an advance over the state-of-the-art knowledge in paleogenomics for its focus on evolutionary process not yet characterized with aDNA (in particular, host-pathogen coevolution), the characterization of the DFE using time-series data, and the development of new resources (datasets and methods). The Amorim Lab is uniquely positioned to accomplish these goals because of our experience in combining model-based approaches with genome data analysis from ancient and modern DNA, as well as our previous experience with the study of medieval Europeans and Native American populations.",,2026,California State University Northridge,358782,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen",2021 +P22698,5R21AI159706-02,"Bacterial activation and evasion of a PP2A phosphatase â€Â"" Pyrin - Gasdermin D axis","Abstract: Many successful Gram-negative pathogens evade or thwart innate immunity via Type III secretion systems (T3SS), often essential for virulence. Yersinia bacteria cause infections such as gastroenteritis and plague, and is an excellent model system for studies of T3SS effects on innate immune responses. Triggering of inflammasome complexes typically culminate with activation of caspase-1 that then cleaves and matures pro- forms of inflammatory cytokines IL-1b and IL-18, cytokines with well-known antibacterial effects, and the pore- forming and pyroptosis-inducing protein Gasdermin D (GSDMD) at residue D276. GSDMD pores also allow passing of IL-1b/IL-18, but the role of GSDMD cleavage in the resistance to many bacterial infections is poorly understood. We have uncovered an extraordinarily complex set of manipulations of inflammasomes by the Yersinia T3SS. One caspase-1 activation pathway is triggered by Yersinia effector YopE, a RhoA inhibitor, and leads to substantial IL-1b/IL-18 release in myeloid cells via Pyrin inflammasomes. Many details of Pyrin activation remain unclear, but Pyrin does not appear to be directly triggered by toxins or effectors such as YopE or Clostridium TcdB, rather by pathological disturbance of host RhoA signaling. Spontaneously activating alleles of Pyrin are also linked to auto-inflammatory diseases such as familial Mediterranean fever. It is believed that inactive Pyrin is phosphorylated, and an unknown phosphatase is needed to trigger Pyrin inflammasomes. Our experiments suggest PP2A phosphatase is involved. We hypothesize that PP2A phosphatase positively regulates bacterial toxin-induced Pyrin activation leading to cleavage of caspase-1, IL-1b and GSDMD. Furthermore, effective inhibitory mechanisms such as those promoted by Yersinia T3SS effector YopM can block this effective anti-bacterial pathway to promote infection. YopM appears to specifically inhibit the T3SS induced Pyrin inflammasome, likely by interactions with several kinases. Our results suggest that attenuated Yersinia strains lacking YopM regain virulence in the absence of Pyrin or GSDMD. Our goal is to decipher the protective mechanisms against infection mediated by PP2A, Pyrin, caspase-1 and GSDMD but suppressed by YopM, in vitro and in vivo. Our work will bridge the gap of knowledge by clarifying key questions related to how Pyrin is regulated by phosphatases and kinases.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,209375,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22699,1C06OD032002-01A1,Expanding UAMS Research Capacity to Establish a Center for Animal Models of Infection and Disease (CAMID),"The University of Arkansas for Medical Sciences (UAMS) is an Institution of Emerging Excellence in a small state with a large rural, underserved population that suffers disproportionately from infectious diseases. UAMS has committed to expanding infectious disease basic research through faculty recruitments but has outgrown current space for high-security biocontainment and animal facilities. This C06 proposal will support the first of 2 phases of renovation of the animal and biosafety level-3 (BSL-3) facilities in Biomedical Research Building I at UAMS and establish the Center for Animal Models of Infection and Disease (CAMID). The CAMID will allow safe and efficient research on highly infectious pathogens, ensure rapid response to new disease outbreaks, and provide new research opportunities by accomplishing the following goals: Goal 1) Expanding capacity for highly infectious disease research. UAMS currently supports 4 research programs that study tuberculosis, plague, COVID-19, and Q fever in a small BSL-3 facility. These renovations will permit needed expansion of these programs and establishment of new pathogen studies by adding 552 sq. ft. of wet laboratory space and doubling animal housing capacity. Goal 2) Establishing a facility for rapid responses to outbreaks and population studies. BSL-2 and -3 space (330 sq. ft. total) termed the Pandemic Response and Public Health Laboratory (PRPHL) will be established to respond to outbreaks needing increased safety precautions and allow new population-based studies. This facility will be optimized for tissue culture and handling human specimens. Goal 3) Expanding the animal facility to study the host response to disease. The UAMS animal facility must be expanded to accommodate researchers' needs. The space proposed for BSL-3 expansion currently houses animals, requiring renovation of new space to recapture this square footage. Proposed renovations will increase animal room and procedural space, expand cage wash capacity, and increase the animal facility by 8,450 sq. ft. Impact of renovations. The proposed increase in animal room space will support current NIH-funded projects and animal model studies by future faculty, and these renovations will enhance UAMS's impact on Arkansans' health by fostering new collaborations with public health researchers. In addition, UAMS has a robust graduate student program that trains students in infectious disease laboratories to become future researchers. The proposed renovations will increase opportunities to train students in animal models of disease.",,2027,UNIV OF ARKANSAS FOR MED SCIS,7975000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Yersiniaceae,,,,,,,,,COVID-19 | Plague | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22702,1R21AI169423-01,Extracellular vesicles released in response to Yersinia pestis,"SUMMARY Extracellular vesicles (EVs) are membrane-bound vesicles released by cells that are potent vehicles for intercellular communication. The signaling capacity of EVs is mediated by incorporation of different biomolecules (e.g. proteins, lipids, nucleic acids, and carbohydrates) within individual vesicles. Neutrophils produce EVs upon recognition of a variety of stimuli, but the biological properties of EVs change depending on the stimuli encountered. Thus, depending on stimulation, neutrophil-derived EVs have been shown to induce both pro- and anti-inflammatory responses in recipient cells. Neutrophils can also produce a subset of EVs that are directly microbiostatic to bacteria and fungi. However, the EV response by neutrophils has only been characterized for very few bacterial species, and therefore, we have a limited understanding of the full potential of neutrophil-derived EVs in response to different bacterial infections. Yersinia pestis is the causative agent of the human disease known as plague. Y. pestis evades immune cell recognition via direct interactions with innate immune cells that disrupt the normal responses by these cells. Specifically, Y. pestis uses a type three secretion system (T3SS) to directly secrete bacterial proteins (called Yops) into host cells, which disrupt specific host cell signaling pathways. The outcomes of Yop translocation into host neutrophils include: blocking phagocytosis, inhibition of the generation of reactive oxygen species, and decreased production of pro-inflammatory cytokines by neutrophils. Recently, we and others have shown that Y. pestis is able to block neutrophil granule exocytosis in a T3SS-dependent manner. Together, these data show that Y. pestis efficiently alters endocytic and exocytic activities by neutrophils. Despite its ability to disrupt endocytic and exocytic pathways, the ability of Y. pestis to alter the production of EVs by host cells has not been previously investigated. With a growing appreciation for EVs in inflammation and bacterial clearance, our lack of a proper understanding of the EVs released by innate immune cells in response to Y. pestis represents a critical knowledge gap in the immune response to Y. pestis. Based on previously published studies and our preliminary data, we hypothesize that Y. pestis actively alters the production of EVs by innate immune cells, and that this alteration has a direct impact on how EVs can influence the immune response to the bacterium. To test this hypothesis, in Aim 1 we will define the composition of the payloads packaged into EVs by neutrophils in response to Y. pestis infection and whether the T3SS and Yop effectors alter the production of EVs. In Aim 2, we will determine the impact of EVs isolated from neutrophils infected with Y. pestis or a Y. pestis strain lacking the Yop effectors on immune cell response to Y. pestis infection. Completion of these Aims will provide for the first time a comprehensive description of the EVs produced by human neutrophils in response to infection with Y. pestis.",,2023,University Of Louisville,234375,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22705,3G20AI167410-01S1,Facility and Building System Upgrades Support for the Howard T. Ricketts Biocontainment Laboratory,"Project Summary/Abstract The Howard Taylor Ricketts Laboratory (HTRL) is a state-of-the-art Regional Biocontainment Laboratory on the Argonne National Laboratory (ANL) campus in DuPage County, Illinois. Located twenty-five miles southwest from the University of Chicago campus, ANL is a federally (Department of Energy) owned site operated by the University of Chicago (UCHICAGO LLC). HTRL is a CDC certified facility owned by the University of Chicago and operated by the Department of Microbiology. Biosafety training and surveillance program involving classroom and laboratory activities ensures that staff, students, and fellows comply with state and federal regulations to safely operate facilities and experiments with RG2, RG3 and Select Agent pathogens. The HTRL construction was completed in 2008. Over the last 13 years, the HTRL has hosted research programs studying the bacterial species Yersinia, Brucella, Coxiella, Rickettsia, Bacilli, MRSA and other ESKAPE organisms, as well as viral pathogens including low and highly pathogenic influenza, DENGUE and more recently SARS- CoV2. The facility currently hosts research program on Plague, Anthrax, MRSA, as well as a Core Research Facility for SARS-CoV2. The HTRL is the largest A-BSL3 holding facility in the region and regularly supports research from consortium institutions including UIC, Northwestern U and Loyola U. The HTRL is fulfilling its goal to rapidly respond to research needs and support biomedical inquiries on emerging and re-emerging pathogens, discovery and testing of new therapeutics and vaccines. The building has been maintained in good working conditions and has been in constant use since its construction. However, with the swelling demands for BSL3 and ABSL3 space and research expertise, the development of new technologies for the study of infectious agents, this proposal is a request (i) to upgrade system and building components for safe research operations, and (ii) to replace research equipment that have either outlived the intended useful life or no longer meet facility requirements.",,2024,University Of Chicago,3293351,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22716,4R00AI147029-04,Quantifying the genetic and environmental factors driving avian influenza spillover,"PROJECT SUMMARY Past influenza cross-species transmission events have lead to devastating human pandemics. H5N1 is an avian influenza virus that has caused recurrent, high pathogenicity human infections since 1997. Humans usually acquire H5N1 through interaction with live birds, and mounting evidence suggests that H5N1 circulation in poultry is strongly linked to human infection. Despite this, the genetic and environmental factors that promote H5N1 circulation in poultry remain unknown. A predominant hypothesis is that wild birds seed new viruses into poultry, and humans acquire infection via poultry interaction. However, the rate of transmission between wild birds and poultry has never been estimated. Although certain husbandry practices like outdoor rearing and transport to large, live poultry markets are hypothesized to enhance H5N1 circulation, the relative contributions of these husbandry practices have never been systematically assessed. Finally, virologic studies have produced a catalogue of mutations associated with human adaptation in laboratory and animal studies, which are currently used to query emerging H5N1 strains and assess pandemic risk. However, many human-infecting H5N1 strains lack known markers of adaptation, and it is unclear whether these mutations predict spillover risk in nature. In this proposal, I will use phylogenetic and statistical methods to determine the genetic and environmental drivers of H5N1 cross-species transmission through 3 specific aims. Completion of these projects with my mentors and co-mentors will allow me to achieve my career goal of transitioning to an independent faculty role by the end of the K99 phase. 1. I will use a recently developed structured coalescent model to estimate the rate of H5N1 transmission between wild birds, poultry, and humans. I hypothesize that cross-species transmission occurs frequently between wild birds and poultry, but only a small subset of lineages circulate long-term. I expect to observe ongoing transmission in poultry, but not in humans. 2. I will use phylogenetic and statistical methods to determine the environmental and husbandry practices that promote long-term H5N1 circulation in poultry. I hypothesize that short-term spillover events will be associated with outdoor poultry housing and rice cropping. Long-term establishments will be correlated with poor vaccination coverage and introduction into a large poultry market. 3. Elucidate genetic and phenotypic determinants of cross-species transmission. I will combine the power of a genome-wide scan with phenotypic validation to identify the genetic correlates of avian influenza spillover. I hypothesize that H5N1 lineages that are prone to human spillover will be enriched for mutations experimentally linked to host switching. I predict that our scan will identify mutations that elicit improved human receptor binding, enhanced replication in mammalian cells, and abrogation of interferon production.",,2024,University Of Pennsylvania,249000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease surveillance & mapping",2022 +P22717,75N93021C00017-P00004-9999-1,NIAID Centers of Excellence for Influenza Research and Response,"CEIRR will determine the molecular, ecologic and/or environmental factors that influence the evolution, emergence, transmission and pathogenicity of influenza viruses, and characterize the immune response to influenza infection to improve understanding of the immune correlates of protection and cross-protection. CEIRR will carry out a host of activities, including cohort studies and human and animal sampling to further understanding of influenza infection, transmission and vaccination; identification of immunological factors that determine disease outcome in the response to influenza infection and vaccination; and studies to determine how influenza viruses evolve, adapt and transmit between humans and at interspecies interfaces.",,2024,Emory University,419873,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2021 +P22718,75N93021C00016-P00005-9999-1,NIAID CENTERS OF EXCELLENCE FOR INFLUENZA RESEARCH AND RESPONSE,"CEIRR will determine the molecular, ecologic and/or environmental factors that influence the evolution, emergence, transmission and pathogenicity of influenza viruses, and characterize the immune response to influenza infection to improve understanding of the immune correlates of protection and cross-protection. CEIRR will carry out a host of activities, including cohort studies and human and animal sampling to further understanding of influenza infection, transmission and vaccination; identification of immunological factors that determine disease outcome in the response to influenza infection and vaccination; and studies to determine how influenza viruses evolve, adapt and transmit between humans and at interspecies interfaces.",,2024,ST. JUDE CHILDREN'S RESEARCH HOSPITAL,6379531,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2021 +P22719,75N93021C00018-P00005-9999-1,CENTERS OF EXCELLENCE FOR INFLUENZA RESEARCH AND RESPONSE,"CEIRR will determine the molecular, ecologic and/or environmental factors that influence the evolution, emergence, transmission and pathogenicity of influenza viruses, and characterize the immune response to influenza infection to improve understanding of the immune correlates of protection and cross-protection. CEIRR will carry out a host of activities, including cohort studies and human and animal sampling to further understanding of influenza infection, transmission and vaccination; identification of immunological factors that determine disease outcome in the response to influenza infection and vaccination; and studies to determine how influenza viruses evolve, adapt and transmit between humans and at interspecies interfaces.",,2024,University Of Georgia,418874,Animals | Human Populations | Viruses | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Environmental stability of pathogen | Disease transmission dynamics",2021 +P22720,75N93021C00015-P00005-9999-1,NIAID CENTERS OF EXCELLENCE FOR INFLUENZA RESEARCH AND RESPONSE (CEIRR),"CEIRR will determine the molecular, ecologic and/or environmental factors that influence the evolution, emergence, transmission and pathogenicity of influenza viruses, and characterize the immune response to influenza infection to improve understanding of the immune correlates of protection and cross-protection. CEIRR will carry out a host of activities, including cohort studies and human and animal sampling to further understanding of influenza infection, transmission and vaccination; identification of immunological factors that determine disease outcome in the response to influenza infection and vaccination; and studies to determine how influenza viruses evolve, adapt and transmit between humans and at interspecies interfaces.",,2023,University Of Pennsylvania,2682037,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2021 +P22722,1R44AI157074-01A1,Development of CM-IAV1 for Treatment of High-risk Pandemic Influenzas,"Project Summary Health and human services (HHS) and the Biomedical Advanced Research and Development Authority (BARDA) have suggested a severe pandemic influenza outbreak is the greatest current threat to national and global security. The Center for Disease Control rates H7N9 as the most threatening of the Influenza A viruses as it, along with H5N1, have fatality rates of ~40% and ~60%, respectively. Models have predicted that an H7N9 pandemic could result in infection of one third of the world population and death of ~40% of those infected, making it the deadliest virus in recorded history (the 1918 flu had a fatality rate of ~2.5%). There is currently no approved therapeutic for severe influenza infection, and in the case of H7N9 ~98% of those infected develop severe infection and require hospitalization. This project seeks to provide some hope of protection in such an outbreak by advancing the most effective broad-spectrum human antibody therapeutic currently available, CM-IAV1. CM-IAV1 is a broadly neutralizing human monoclonal that is cross-reactive for group 1 and group 2 avian influenza. CM-IAV1 has already been shown to protect mice against lethal (non- laboratory strain) H7N9 and H5N1 when given in a single dose 72 hours post-infection. To leverage this outstanding preclinical data, we have assembled a world-class team that is focused on advancing CM-IAV1 into the clinic. The experiments presented in this application will take a promising preclinical agent and, together with our continued and parallel investments, create a clinical asset with enormous potential to reduce morbidity and mortality associated influenza infection from the most relevant CDC- prioritized pandemic strains. We believe that development of this antibody, at this time, and by this team represents the best hope of offering meaningful lifesaving protection against the terrifying possibility of a global Influenza A outbreak. The overarching goal of this project is to advance a novel broad-spectrum, lifesaving therapeutic for pandemic influenza A infection from promising preclinical candidate through investigational new drug (IND)-enabling studies to IND filing.",,2023,"CELDARA MEDICAL, LLC",300000,Other | Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Orthomyxoviridae,H5 | H7,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",,2022 +P22723,5R21AI151418-02,Sex-specific Immune Responses to Severe Influenza Virus Infection,"Sex-specific Immune Responses to Severe Influenza Virus Infection ABSTRACT Men and women experience influenza virus infection differently, with women often experiencing a more severe infection. Lung immunopathology is a major contributing factor to influenza virus disease severity and has been linked to differential disease outcomes in men and women. The differences between male and female immune responses during infection are the immune response dynamics, i.e. the speed and magnitude of the reaction of key immune molecules and cells to the virus. These dynamics are regulated by the molecular and cellular interactions that comprise the lung immune system, and it has been shown that lung immune dynamics can be altered in women by altering levels of circulating sex steroids (estradiol) to affect lung inflammation and overall infection severity. Here, we propose an experimental and computational modeling study to quantify the differential immune kinetics that drive the distinct lung immunopathological outcomes observed between men and women. Human male and female infection outcomes have been recapitulated in mouse models. We will infect male and female mice with a moderate pandemic H1N1 virus and a deadly avian influenza virus, collect dynamic immunologic and hormone data, and train mathematical models to the data to quantify the immune kinetics regulating the differential dynamic lung immune responses observed between the sexes. The immunologic data will include major cytokines and immune cells with established significance to virus clearance and respiratory tissue inflammation. Successful completion of the research program will provide the first sex- specific mathematical models of influenza-induced immune responses, the first mathematical models of the avian influenza induced immune response, and the first mathematical models quantifying the impact of sex hormones on lung immune regulation in females. By quantifying which immune kinetics are different between males and females during moderately and severely pathogenic infections, we will generate novel hypotheses on the molecular/cellular origins of lung immunopathology during influenza infection and provide quantitative evidence on whether mechanisms promoting severe lung pathology are dependent on sex, virulence of the virus, or both factors. And quantifying the relationship between sex hormones and lung immune activity in females may provide insight into the mechanisms associated with the increased susceptibility experienced by pregnant women during severe influenza virus infection.",,2023,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,148510,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | Other,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P22724,1DP2AI175474-01,Structure and dynamics of RNA elements regulating viral aberrant RNA synthesis,"SUMMARY Seasonal influenza viruses cause >600 million cases annually and hundreds of billions of dollars in losses. Pandemic and avian influenza viruses present an even greater threat because they can dysregulate our immune response and/or spread to and shut down multiple organs. Current evidence suggests that aberrant viral replication contributes to a dysregulating of the innate immune response and the emergence of highly pathogenic strains from low pathogenic precursors. The transition from a low to highly pathogenic virus involves insertion of multiple basic amino acids in the cleavage site of the viral hemagglutinin (HA) surface protein. In birds, this change in HA allows the virus to spread systemically, resulting in mortality rates of up to 100% in poultry. The molecular mechanism underlying insertion of amino acids in the cleavage site is not well understood, but it may involve stuttering of the RNA polymerase in the HA gene, resulting in nucleotide insertions. The viral RNA polymerase can also delete nucleotides from the viral genome, resulting in shorter aberrant RNAs. Recent studies have shown that pandemic and avian influenza A virus infections produce RNA molecules of about 56-125 nucleotides in length, called mini viral RNAs, and that their synthesis is correlated with the upregulation of disease markers. How the RNA polymerase makes such large deletions in the viral genome is not known. This project will use a novel method to stall the viral RNA polymerase during key steps of viral replication and aberrant RNA synthesis, and use state-of-the-art biochemical, biophysical, and structural approaches to reveal the steps of viral replication and genome encapsidation, as well as aberrant RNA synthesis. In doing so, this project will contribute to a complete mechanistic understanding of influenza replication and answer long-standing, fundamental questions about the emergence of highly pathogenic influenza viruses.",,2025,PRINCETON UNIVERSITY,1412295,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22725,5R01AI147497-03,Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine,"ABSTRACT The WHO estimates there are approximately 5 million cases of influenza infections annually, with approximately 500,000 deaths occurring globally. The most cost-effective protection against influenza is vaccination. Unfortunately, due to yearly antigenic shifts and drifts, current seasonal vaccines are ineffective. There is a need for a better flu vaccine. In order to design a better flu vaccine, we plan on optimizing the immune synapse using nano/microparticles (MPs) fabricated from the polymer acetalated dextran (Ac-DEX). Our previous data has shown a dependence of particle degradation and optimal immune response against an influenza antigen. Not only does the release of the antigen effect the immune response, the release of the adjuvant is also important. The optimized degradation of both adjuvant and antigen has a drastic change in survival compared to non- optimized formulations. Our particle system is unique because it relies on the highly tunable polymer Ac-DEX. Ac-DEX is ideal for delivery of agents to phagocytic cells because it is acid-sensitive and has significantly increased degradation in the low acid (~pH 5) of the phagosome. In addition to this it has tunable degradation rates that can range from hours to months, which is a unique range from commonly used polyesters (e.g. poly(lactic-co-glycolic acid) (PLGA)) that have degradation on the order of months. Moreover, Ac-DEX is unique from polyesters because its degradation products are pH neutral, and do not have the potential to shift the local pH or damage sensitive payloads. We have three specific aims exploring various optimizations of our particle system. Aim 1 is focused on formulation of the polymer and particles. The release rate of the adjuvant will be explored. Ac-DEX polymer with various cyclic acetal coverages will be fabricated to degrade over a broad range of times. In Aim 2 we will evaluate the effect of loading of a novel influenza antigen either on the surface or encapsulated into the MPs. We will explore degradation rates on antigen release as well as delivery routes in determining the optimal delivery of influenza antigens that provide a broad range of protection. In Aim 3 we will explore our optimized system in protecting ferrets. Ferrets are the ideal large animal model for influenza infection. Using this model, we will evaluate the vaccine efficacy of our formulation, in comparison to a commercially available flu vaccine.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,568652,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P22726,5R21AI144135-02,Mimicking evolution to define mechanisms of airborne transmission of H7N9 viruses,"The Asian lineage H7N9 avian influenza viruses (AIV) have caused >1500 human zoonotic infections with 615 deaths. These viruses have not spread in humans; however, there is a high potential for these viruses to evolve to transmit via the airborne route and cause a pandemic. Using ferrets, we previously evaluated the ability of the prototypic Asian lineage virus, A/Anhui/1/2013 (H7N9), to undergo two continuous rounds of airborne transmission. In these studies, we found that the virus was able to transmit to 50-66% of respiratory contact ferrets during both rounds of transmission. In a subsequent deep sequence analysis, we identified 2-5 mutations in 90-99% of all variant viruses that transmitted. These mutations were in the hemagglutinin (HA), neuraminidase (NA), and viral polymerase genes. As airborne transmission is associated with enhanced binding and replication in cells of the upper airways, we hypothesize that the identified mutations will alter the molecular properties of the virus to enhance replication in primary human nasal and tracheal epithelial cells. Our aims are: Aim 1. Determine the role of previously identified HA and NA mutations in an H7N9 virus with the A/PR/8 vaccine backbone. Viruses carrying the H7N9 HA and NA on the A/PR8 vaccine backbone will generated. Mutations will be introduced into the HA and NA gene segments and several properties including receptor-binding preference, pH of fusion, thermostability, NA activity, and changes in antibody recognition via immune serum will be evaluated. Aim 2. Evaluate the role of previously identified mutations on the viral polymerase. To assess the impact of mutations in the viral polymerase, in vitro polymerase reconstitution assays will be performed. Specifically, the activity of the wild-type H7N9 polymerase with and without the identified mutations will be assessed. Aim 3. Determine if the introduction of previously identified mutations alters viral replication in primary human airway epithelial cells. To determine if the identified mutations impact viral replication, we will evaluate the replication kinetics of recombinant H7N9-A/PR8 viruses for their growth in primary human airway epithelial cells. Primary human cells will include nasal, tracheal, bronchial, and small airway epithelial cells. Collectively, these studies will determine the effect of the identified mutations on different molecular properties of the virus, while also determining if the mutations alter the viral tropism in human cells. Our findings will generate new insight on how AIV evolve to transmit via the airborne route and will yield critical knowledge required to interpret the evolution and assess the pandemic potential of H7N9 viruses.",,2024,"PENNSYLVANIA STATE UNIVERSITY, THE",186177,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H7,,,,,,H7N9,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P22732,1R01GM143773-01A1,Biophysical studies of viral membrane fusion proteins,"SUMMARY Influenza A virus (IAV) hemagglutinin (HA) is the canonical example of a class-I viral fusion protein, and thus provides an ideal model system for understanding the fusion mechanisms of many different viruses. Numerous other viral envelope glycoproteins, including the SARS-CoV-2 spike, are believed to mediate fusion by a comparable mechanism. Our long-term goal is to establish a complete mechanistic framework of class-I viral fusion. We further aim to identify conserved and divergent features of the fusion mechanisms of distinct viruses, generating specific models that fit within the general framework. HA resides on the surface of the IAV virion and facilitates attachment to the target cell surface through the receptor-binding domain (HA1) engaging SA moieties. Following endocytosis and trafficking to the late endosome, HA promotes fusion of the viral and endosomal membranes. The model of HA-mediated membrane fusion describes a “spring-loaded” metastable prefusion conformation at neutral pH. Dissociation of HA1 from the fusion domain (HA2) allows HA2 to undergo a cascade of conformational changes that drive membrane fusion. While extensive structural data exist for HA pre- and postfusion, and alternative conformations have been visualized and inferred, the conformational trajectory that leads to membrane fusion, including the adoption of anticipated intermediates, has never been explicitly validated. Nor has the order and timing of conformational changes and membrane fusion been determined. Here, we will utilize a multifaceted approach involving single-molecule Förster resonance energy transfer imaging, single-virion fusion, cryoelectron tomography, and molecular dynamic simulation to directly visualize the conformational trajectory undergone by HA during membrane fusion. We will explore the roles of virion morphology, HA density and cooperativity, and target membrane lipid content in mediating HA conformational changes and the mechanism of fusion. We will describe the allosteric connection between distal regions of HA that regulate the timing of fusion, drawing comparison to SARS-CoV-2 S. Finally, we will biophysically characterize the phenotypic differences between human and avian IAV strains to determine what prevents avian IAV strains from entering the human population.",,2026,UNIV OF MASSACHUSETTS MED SCH WORCESTER,502500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22735,1R01AI165692-01A1,Automated chemo-enzymatic synthesis of N-glycans for host-pathogen interactions,"SUMMARY Numerous viruses initiate infection by binding to cell surface glycans of the host. The selectivities of viral receptor binding proteins for specific glycans critically determine host range, tissue- and cell tropism and pathogenesis. A detailed understanding of receptor usage by respiratory viruses is critical for the development of surveillance, prevention and intervention strategies to mitigate risks of future pandemic outbreaks. Glycan receptor usage by respiratory viruses have been difficult to probe because of a lack of appropriate panels of glycans for structure-activity studies. The latter is due to limitations in synthetic methodologies that do not permit the preparation of large panels of biological relevant glycans. In this program, chemoenzymatic methodologies will be developed that make it possible to prepare a wide range of N-glycan found in the respiratory tract of human and relevant animals. It is based on a new synthetic paradigm, which we coined “Stop-and-Go-Chemoenzymatic Glycosylation”. It uses chemically modified sugar nucleotide donors that can be employed by relevant glycosyl transferases to give products in which particular residues are temporarily blocked from further enzymatic modification. At an appropriate stage of synthesis, the blocking group can be removed to give a natural glycan. The speed of glycan synthesis will be increased by developing an automation platform that can perform enzymatic and chemical manipulations. The new methodologies will be used to prepare a collection of complex N-glycans that resemble structures expressed by respiratory tissue for host-pathogen studies. In this application, the collection of glycans will used to examine in detail receptor usage of influenza A viruses. The glycans will be printed as a microarray to probe binding specificities of human and animal influenza A viruses. Selected compounds will be examined in dynamic binding assays to establish the interplay between hemagglutinin (HA) and neuraminidase (NA) activity. The proposed studies will uncover unique traits of human and animal IAVs, which will facilitate the implementation of surveillance, prevention and intervention strategies to mitigate risks of future pandemics. The result of the studies will be exploited to develop an array-based system to antigenically characterize IAVs, which will greatly facilitate strain selection for seasonal flu vaccination. 1",,2027,University Of Georgia,469846,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P22740,1F32AI152298-01A1,Identifying Intermolecular Constraints on Influenza Virus Evolution,"PROJECT SUMMARY/ABSTRACT The long-term goals of the candidate are to establish an independent research laboratory investigating host adaptation of zoonotic viruses. This proposal outlines a set of aims that will provide a foundation for a career as a professor at an academic institution. The candidate has established a training plan comprising five main areas: coursework in computational biology, mentorship under a diverse and supportive network of University of Pittsburgh faculty, publication of research in peer-reviewed articles, networking at seminars and conferences, and application for transitional funding and faculty positions. The candidate has assembled a diverse mentoring committee to achieve these goals: Dr. Seema Lakdawala, the primary sponsor; Dr. Vaughn Cooper, co-sponsor of this application; Dr. Erik Wright, collaborator; and a formal mentoring committee including Drs. John Williams, Neal DeLuca, Matthew Nicotra, and Anne-Ruxandra Carvunis. See co-sponsor statement and letters of support. The research objectives proposed in this application include the investigation of the role of complex interactions on influenza virus evolution. Protein-protein interactions determine whether polymerase subunits are compatible, and recently described RNA-RNA interactions are theorized to drive genomic assembly of viral RNA segments into daughter viruses. However, the impact of such complex interactions on viral evolution are not well understood. Such knowledge will ultimately aid in the prediction of how genetic reassortment of genomic segments occurs between two influenza virus strains, a process that leads to emerging pandemic and zoonotic strains. These objectives are in accordance with the mission of the NIAID to better understand and prevent infectious diseases. We hypothesize that evolutionary relationships predict complex interactions among viral RNA and protein that constrain reassortment. We present the following aims to address this hypothesis: Aim 1. To define the mechanism of evolutionary constraints on RNA-RNA interactions in seasonal human IAV. We will identify nucleotide residues underlying our initial observation that parallel evolution occurs between viral RNA and examine their roles in genomic packaging. Aim 2. To examine parallel evolution between protein subunits of avian polymerase complexes. We will test whether complex protein-protein interactions similarly constrain avian influenza virus evolution. These aims will provide a basis for the candidate to launch an independent laboratory distinct from that of her advisor investigating evolutionary constraints on host adaptation of zoonotic viruses. The sponsor, co-sponsor collaborator and mentoring committee are all present at the University of Pittsburgh and can provide the support necessary for this candidate to succeed.",,2022,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,27941,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P22742,1R21AI166906-01A1,A revised model for immune imprinting by influenza virus,"PROJECT SUMMARY Immune imprinting by influenza virus has been described as a lifelong bias in immune memory of, and protection against, influenza strains encountered in early childhood. It has become an increasing focus in the field of influenza research. Immune imprinting has been thought to reflect unique events associated with early life infections and is viewed primarily as a function of B cell memory. In this proposal, we will test that many of the findings that have been attributed to the earliest infections can in fact be explained to a significant degree by an alternate mechanism involving CD4 T cell specificity and functionality that occurs during the first infection and that biases the responses to all influenza infections that occur thereafter. The proposed model, drawn from much of our accumulated research, will be tested by a series of experiments whose goal is to determine whether establishing pre-existing immunity with exclusive and selective lung- initiated CD4 T cell priming, followed by virus infection challenge, will mimic many of the features of immune imprinting. Novel molecular and intranasal vaccine strategies will be used to selectively prime the respiratory tract and CD4 T cell compartment for selected influenza epitopes by delivery into the respiratory tract. We will test whether priming subtype-specific HA CD4 T cell responses and CD4 T cells specific for epitopes that are conserved across influenza A subtypes can mimic influenza imprinting with regard to the biases in CD4 T cell and B cell responses and protection that occur upon influenza virus challenge. These issues will be addressed through completion of two Specific Aims: Specific Aim 1. Derive and test constructs encoding influenza-CD4 peptide epitopes and evaluate epitope specific priming via intranasal vaccine platform Specific Aim 2. Test of CD4 T recall responses to infection, antibody responses and protection Collectively, completion of these experiments have the potential to fundamentally change our understanding of what has been viewed as significant obstacle in human protective immunity to influenza and will offer strategies to overcome the deficiencies in the host that lead to the deleterious effects of imprinting.",,2024,University Of Rochester,249731,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22748,5F31AI150114-03,Virus-host interactions underlying species specificity of influenza A virus gene expression,"PROJECT SUMMARY Devastating influenza A virus (IAV) pandemics arise when non-human adapted strains overcome human species barriers to successfully infect and sustain human-to-human transmission. The novelty of a pandemic strain poses a substantial burden to human health leading to increased incidences of severe respiratory complications, hospitalizations, and death when compared to seasonal influenza. The most recent pandemic in 2009 (pH1N1) arose from a reassortant swine IAV that contained human, swine, and avian adapted gene segments. To understand how these pandemic IAVs overcome species barriers, we must understand the mechanisms that lead to viral adaptation to human hosts. Recent work in our lab has demonstrated that regulation of gene expression from the IAV M segment plays a role in host adaptation. The IAV M segment encodes two major proteins by alternative splicing. Matrix 1 (M1) gives the virion its structure and is encoded by the colinear mRNA, and M2, which is needed for viral replication, is encoded by a splice product of the M1 mRNA. We have used reverse genetics to engineer recombinant viruses that share seven of the eight IAV gene segments but differ in the origin of the M segment, allowing us to evaluate properties of this segment. Recombinant viruses carrying avian or human adapted M segments replicate to similar titers and express similar levels of M1 and M2 protein when infecting avian cells. However, in human cells, the avian M segment virus replicates less efficiently and expresses significantly higher levels of M2 mRNA and protein than the human M segment virus. Mammalian adapted M segments maintain low levels of M2 in human cells. These data lead to my hypothesis that, following introduction into mammalian hosts, mutations to the avian IAV M segment are needed to re- establish optimal virus-host interactions important for regulation of M2 expression. In Aim 1, I will map the M sequence determinants that underly differential M gene expression between avian and mammalian adapted M segments. I have used reverse genetics to generate avian M segment viruses that carry nucleotide mutations identified in the pH1N1 M segment. I will infect human cells with these viruses. Then I will evaluate the impact of these mutations on avian and human adapted M1 and M2 mRNA and protein steady state levels and stability. In Aim 2, I will investigate the role of host factors in differential M2 expression between avian and human adapted M segments. I will determine the binding affinities of avian and human M1 mRNAs with host splicing factors using biochemical methods and evaluate subcellular localization of M1 and M2 mRNAs during infection by microscopy. Through these experiments, I will elucidate the molecular mechanisms that underly the species specificity IAV M segment gene expression. These studies will reveal additional mechanisms of IAV adaptation to human hosts, which could be used to better assess the pandemic risks of future IAV zoonoses.",,2023,Emory University,33939,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P22752,1R21AI166006-01A1,Evaluation of Artemisia as an Effective Combination Therapy Against SARS-CoV-2 Infection,"ABSTRACT Viruses are cleverly dangerous; they jump from species to species, mutate to evade vaccines and single antiviral drugs, and cause many human diseases and deaths. A notorious current example is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). As we witness daily, the coronavirus pandemic reveals gaping holes in the US healthcare system and how woefully unprepared we are for wide-spread viral outbreaks. Two years into the pandemic we have three antiviral drugs (remdesivir, molnupiravir, and paxlovid and a single anti-inflammatory (dexamethasone). Thus, there remains an unmet need for drugs to fight the virus and the inflammatory sequelae of infection. Recently available vaccines comprise a boon to stopping this pandemic, but rollout, distribution, vaccine hesitancy, and the continuing emergence of variants of concern (VOC) hinder progress towards this goal. Because of these uncertainties, many people have turned to natural products with the hope that these untested supplements will keep them safe and healthy. In fact, nearly 20% of the US population uses natural products (including plant-based or botanical preparations) for treatment or prevention of disease. The use of plant-based medicines is even more prevalent in resource-limited countries, where for many people they constitute a primary health care modality. This R21 proposal stems from the recent finding by our team that extracts from the plant Artemisia annua L. (Asteraceae) (aka A. annua, qinghao, sweet wormwood, annual wormwood, sweet annie), potently inhibits wild type SARS-CoV-2 and VOC infection in vitro. Based on our recently published and preliminary data, we hypothesize that A. annua contains mixtures of compounds that synergistically inhibit SARS-CoV-2 and virus-induced inflammation in vivo. To address the hypothesis, the Weathers, Polyak, Fuller, and Kellogg labs will merge their complementary expertise in plant ethnopharmacology the pharmacology of historically used medicinal plants), in vitro and in vivo virology, and natural product chemistry, and to conduct two Specific Aims that will demonstrate the in vivo antiviral activity of A. annua extracts in the human ACE-2 transgenic mouse model of SARS-CoV-2 infection and disease (AIM 1). We will also a) define the natural product(s) that confer antiviral activity, b) whether virus suppression arises through synergistic combinations of compounds in A. annua, and c) begin to decipher mechanisms of antiviral action (AIM 2). As such, this project is expected to provide new tools for the battle against COVID-19 and potentially enhance global preparedness for the next virus outbreak, which history has taught us will most certainly occur.",,2024,"PENNSYLVANIA STATE UNIVERSITY, THE",239586,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2022 +P22758,5G13LM013554-02,Sickness and Power: The Great North American Epizootic Flu of 1872,"Project Summary The recent outbreak of COVID-19 and the upswing in seasonal influenza this winter offer pressing reminders of the enduring, even intensifying dangers that emergent zoonotic diseasesâ€Â"" disorders caused by pathogens that jump across species dividesâ€Â""pose to human health. Historians of medicine and other scholars have long recognized the power of such diseases to shape human history. Yet few works in epidemiological history have attended to the complicated relationships that continue to link pathogens, humans, other-than-human animals, and the natural and built ecosystems that connect the livesâ€Â""and, often, the deathsâ€Â""of these disparate organisms. This proposal seeks to remedy this gap by supporting the completion of a Geographic Information System (GIS) and scholarly book examining the Great Epizootic Influenza of 1872. This little-known disease event began in Toronto’s market-farming hinterland, where the continuous exchange of pathogens between humans, horses, other farm animals, and wild waterfowl set the stage for the evolution of a new and unprecedentedly virulent form of influenza A virus. Within weeks, swarms of the new virus had engulfed metropolitan Toronto. It took just another month for the disease to spread throughout southeastern Canada and the northeastern U.S. By summer 1873, flu had sickened well over 90% of the horses, mules, and asses in the U.S., Canada, Cuba, Mexico, the Indigenous Nations of the West, and parts of Central America. As it achieved continental proportions, the Great Epizootic prompted economic paralysis, debate about the malady’s nature and treatment, and more than a little soul-searching over human use and misuse of “the noble horse.” Although the disease seemed to dissipate in fall 1873, recent scientific studies strongly suggest that the new flu type responsible for the Great Epizootic lived on and continued to adapt. Descendants of this viral type went on to develop the ability to infect human populations, too, most notably in the Great Pandemic of 1918-’20, a worldwide influenza outbreak that killed at least 50 million people. This proposal supports research in historical documents, the integration of evidence from these primary sources into a Geographic Information System (GIS), and the completion of a scholarly book that casts the Great Epizootic Flu as an unheralded but momentous event in disease history. Employing methodologies and findings from virology, evolutionary ecology, animal behavior, environmental history, and other fields, and adopting a transnational perspective that tracks this outbreak across regional, national, and tribal boundaries, this book offers fresh insights into the past, present, and future of influenza and the many other infectious diseases that don novel configurationsâ€Â""and hence new powers to endanger human and animal health alikeâ€Â""by passing from species to species.",,2024,UNIVERSITY OF COLORADO,47922,Other,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Secondary impacts of disease, response & control measures",Animal source and routes of transmission | Disease surveillance & mapping | Social impacts | Economic impacts,2021 +P22759,5R01AI153098-03,Triggering germline-encoded broadly neutralizing antibody responses against influenza virus,"Project Summary / Abstract This is an application by Dr. Daniel Lingwood and Dr. Facundo Batista, faculty members of the Ragon Institute of MGH, MIT and Harvard. Both investigators define B cell-antigen recognition principles to inform antibody vaccine design, and for this, have developed two orthogonal transgenic mouse models that recapitulate human antibody responses in vivo. The investigators propose to apply these models to evaluate germline stimulation of human B cell lineages known to give rise to broadly neutralizing antibody (bnAbs) against influenza A viruses (IAV), which account for the majority of flu-hospitalizations and pandemic threats. Most antibody responses to IAV are dominated by off-target, non-neutralizing activities, however, work from the investigators indicates that human BCRs assembled from the antibody VH gene, IGHV1-69, possess natural specificity for a conserved site of vulnerability, the stem-bnAb epitope on the hemagglutinin spike proteins from Group 1 IAV (IAV subtypes: H1, H2, H5, H6, H8, H9, H11, H12, H12, H16). To test if this genetically endows for vaccine- amplifiable bnAb development pathways, the investigators have engineered the LINGWOOD mouse system, where antibodies develop with human antibody VH genes (e.g. IGHV1-69) and full human CDRH3 diversity. Genetic manipulation of this system enables in vivo B cell titration to match the IGHV1-69 B cell frequency found in humans. Sequentially immunizing these mice with SS-np, a nanoparticle displaying the bnAb target, has succeeded in germline stimulation of IGVH1-69 bnAb precursors and IGHV1-69-dependent expansion of bnAb responses; the first example of eliciting high titer IAV bnAbs through vaccination. This response also provided broad protection against Group 1 IAV, including pandemic bird flu, supporting the investigators' central hypothesis that broadly protective bnAbs can be elicited by germline antibody-targeting vaccines. In Aim 1, the investigators will define whether SS-np stands as a universal booster of the IGHV1-69-encoded bnAb response after introduction of B cell memory to diverse IAV `swarms' that simulate human immune history to influenza. In Aim 2, the investigators will define how refocusing serum antibodies against this specific bnAb target also enhances antibody Fc effector functions, potentially co-enabling protection through activation of innate immunity. In Aim 3, the BATISTA mouse system will be used to evaluate vaccine-expansion of IGHV1-69 bnAbs alongside the human IGHV1-18- and IGHV6-1-class bnAb lineages, which neutralize the remaining Group 2 IAV subtypes (H3, H4, H7, H10, H14, H15). In this system, murine IgM B cells bearing individual human bnAb precursors of each pathway are co-transferred to a single recipient mouse. Following immunization, lineage expansions are individually tracked via their progression through B cell germinal centers and then into immune memory. The animals will be co-immunized with SS-np, SS-np2, and SS-np3; three geometrically identical nanoparticles bearing distinct affinities for each bnAb precursor. Selective + collective expansion of these bnAb lineages aims to overcome failure of traditional influenza vaccine approaches.",,2024,MASSACHUSETTS GENERAL HOSPITAL,520617,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H3 | H7 | Other,,,Unspecified,,,Unspecified,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Vaccine design and administration",2020 +P22765,1R43AI167158-01A1,Rapid response to pandemic influenza via multi-antigen RNA-based vaccine,"Project Summary The proposal is to develop an RNA-based, rapid-response influenza vaccine prototype, supporting NIAID’s call for nucleic acid-based vaccines that protect against pandemic influenza threats. Avian influenza A H7N9 causes severe respiratory illness with a high mortality rate. The virus’ high zoonotic capacity has raised serious concerns over the possibility of a pandemic, with the risk being potentially similar to that of H5 strains. While progress has been made in the development of H5 influenza vaccines, H7 products have lagged. The proposed H7N9 vaccine will be innovative in two respects. 1) H7N9 vaccines typically focus on the hemagglutinin (HA) protein as the main immunogen, but immune responses to HA H7, while protective, are weaker than those against other HAs in humans. Therefore, Tiba will develop a multi-antigen approach, specifically including optimized ratios of the virion proteins HA, NA, M1, and NP. This approach is expected to increase the immunogenicity and heterotypic protective potential of the vaccine. 2) Conventional lipid nanoparticles (LNPs), which are the mainstay of nucleic acid delivery, require a large proportion of “structural” lipid, resulting in a relatively low RNA content. Tiba has developed a modified dendrimer nanoparticle system that maximizes the delivered RNA mass content, protecting RNA from degradation, and enables efficient uptake by cells in vivo. The prototype composition developed here will serve as a platform into which any outbreak antigen sequences could be rapidly implemented. Tiba will meet the near-term goal of developing a prototype HA/NA/M1/NP vaccine to advance toward live virus challenge experiments and IND-enabling studies in Phase 2 by completing three Phase 1 Aims. The first is to validate performance of a H7 HA replicon RNA-based expression construct in vivo. This will be generated and formulated with Tiba’s delivery system and tested in BALB/c mice at 0.2 Ã'µg, 2.0 Ã'µg, and 20 Ã'µg to measure cellular and humoral immunogenicity. These studies will establish the minimum dose required for subsequent experiments. In the second Aim, Tiba will generate and test individual formulations of NA, M1, and NP mRNA and replicon candidates, validating their performance in vivo at similarly increasing doses by T cell ELISpots and, for NA, also by ELISA to measure antibody responses. The final Aim is to compose a multi-antigen prototype vaccine combining the optimal balance of HA replicon RNA with NA, M1, and NP RNAs by co-encapsulating the four payloads in a single nanoparticle formulation. This multi-antigen candidate vaccine will be tested in male and female BALB/c mice, in comparison to HA-only and irrelevant antigen-coding control vaccines to determine if immunogenicity is retained against all components, and if anti-HA responses benefit from inclusion of the additional virion proteins. The candidate prototypes will be compared to state-of-the-art LNP formulations to evaluate the performance of Tiba’s delivery technology compared to the current gold-standard for RNA vaccines.",,2022,"TIBA BIOTECH, LLC",284906,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H7,,,,,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P22766,1R01AI167910-01,Sequence-function relationship of influenza broadly neutralizing antibodies,"PROJECT SUMMARY Influenza A virus continues to be a major global health concern due to antigenic drifts and shifts. Rapid antigenic drifts of circulating human influenza subtypes (H1N1 and H3N2), which are caused by point mutations, can drastically hamper vaccine effectiveness despite annual update of the seasonal influenza vaccine. On the other hand, antigenic shifts, which are caused by genetic reassortment between antigenically distinct strains, can result in devastating pandemic as exemplified by the 1918 Spanish flu. Human infections with different zoonotic subtypes, such as H5N1, H6N1, H7N9, H9N2, and H10N8 have also been reported. As a result, a universal influenza vaccine that can elicit broadly protective antibody responses to diverse influenza strains and subtypes is urgently needed. The discovery of broadly neutralizing antibodies (bnAbs) that target the conserved stem region of influenza hemagglutinin (HA) has raised the possibility of developing a universal influenza vaccine. A number of HA stem bnAbs are encoded by immunoglobulin heavy chain germline gene IGHV6-1. Since these IGHV6-1 HA stem bnAbs can be found in multiple individuals and can cross-react with both group 1 HAs (H1, H2, H5, H6, H8, H9, H11, H12, H13, and H16) and group 2 HAs (H3, H4, H7, H10, H14, and H15), they represent the type of antibody response that needs to be induced by a universal influenza vaccine. This proposed study will use innovative high-throughput experiments to define sequence features in the heavy-chain complementarity-determining region 3, light chain, and somatic hypermutations, that enable an IGHV6-1 antibody to be a cross-group HA stem bnAbs. The underlying molecular mechanisms will be further characterized by structural biology approach. The results will help accurately estimate the germline frequency of IGHV6-1 HA stem bnAbs and understand their affinity maturation pathway, which in turn will benefit the design of a universal influenza vaccine. Furthermore, the experimental framework established in this study will be applicable to characterize any antibody of interest.",,2026,UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN,459505,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2022 +P22768,5R01AI154656-02,Seasonal and universal Vaccination in aged populations with pre-existing immunity,"PROJECT SUMMARY Current influenza (flu) vaccination based on hypervariable hemagglutinin (HA) protein fails to provide effective cross protection. The efficacy of vaccination is low in the aged populations even with pre-existing immunity. The impacts of pre-existing immunity on the immunogenicity and efficacy of universal and seasonal vaccination largely remain not well understood in the aged populations. Development of new flu vaccines and vaccination strategies improving cross protective efficacy in young naïve and aged hosts with pre-existing immunity is of high priority. Mono conserved antigenic targets inducing cross protection tested in naïve animal models include the flu A virus M2 extracellular domain (M2e), HA-stalk domains, and neuraminidase (NA) were reported but insufficient for translation to humans. The multi-target universal vaccines in naïve and aged hosts with pre-existing immunity remain to be developed. We developed heterologous tandem repeat of M2e (5xM2e) presented on immunogenic virus-like particles (5xM2e VLP). Vaccination with 5xM2e VLP was effective in broadening cross protection but suboptimal. A further improved universal vaccine should be developed. Our preliminary studies found synergistic effects on improving cross protection by both M2e and NA immunity. Therefore, as a new universal vaccine candidate, we developed a multi NA + 5xM2e VLP vaccine containing multi-subtype NA and 5xM2e on the same VLP particle. In addition, we newly designed genetically linked novel recombinant M2e-stalk universal protein vaccines effectively inducing both M2e and HA-stalk immunity and conferring broad cross- group protection. Adjuvanted universal vaccination will overcome the aging-related immune senescence by activating T and B immune cells in naïve hosts or aged populations under pre-existing immunity. In this project, we will test the hypothesis that new universal vaccination inducing multi immunity (M2e, Stalk, NA) will enhance the breadth and efficacy of cross protection in adult and aged populations with or without pre-existing immunity. Under Aim 1, we will determine the efficacy of multi-target universal vaccines in young adult mice and ferrets under naïve and pre-existing immune conditions. In Aim 2 studies, we will determine the durability of cross protective immunity by multi targeting new universal vaccines and test a vaccination strategy enhancing cross protection in aged mouse and ferret animal models. In the Aim 3, we will investigate cross protective immune mechanisms of multi targeting universal vaccination in young and aged mouse models. The outcomes in this project will be highly significant in the aspect of translational science and relevance to improve the cross protective efficacy of flu vaccination.",,2026,GEORGIA STATE UNIVERSITY,542726,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity,2021 +P22771,3UM1AI148373-03S4,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2023,KAISER FOUNDATION RESEARCH INSTITUTE,82895,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Therapeutic trial design | Vaccine trial design and infrastructure,2021 +P22772,3UM1AI148373-03S2,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2023,KAISER FOUNDATION RESEARCH INSTITUTE,314872,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Therapeutic trial design | Vaccine trial design and infrastructure,2021 +P22773,3UM1AI148373-03S5,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2023,KAISER FOUNDATION RESEARCH INSTITUTE,663266,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2021 +P22774,3UM1AI148373-03S3,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2023,KAISER FOUNDATION RESEARCH INSTITUTE,243453,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Therapeutic trial design | Vaccine trial design and infrastructure,2021 +P22776,5R21AI163822-02,Regulation of Cell Death and Inflammation by ISG15 during SARS-CoV2 Infection,"SARS-CoV2 is a highly contagious, novel human coronavirus that causes coronavirus disease 2019 (COVID-19). Currently over 7.4 million people in the US have confirmed infection with SARS-CoV2 and over 215,000 have died. Severe COVID-19 is characterized by pulmonary and systemic inflammation and multi-organ dysfunction, which disproportionally affects elderly patients. The mechanism by which SARS-CoV2 triggers such severe pathogenesis is poorly understood. Recent clinical studies have suggested that cell death, especially the induction of necroptosis, may be predictor of severe COVID-19 disease. The mechanism by which the host restricts necroptosis is unclear. In the preliminary data we have shown that the interferon induced protein, ISG15, acts as a negative regulator of necroptosis and its downstream inflammatory responses during viral infection. In this proposal we will test the hypothesis that SARS-CoV2 induces necroptosis and that ISG15 functions as a negative regulator of necroptosis in respiratory epithelial cells. We will use in vitro primary tracheal epithelial cultures (hTECs) and an in vivo mouse adapted SARS-CoV2 animal model to ask several questions including: 1) Does SARS- CoV2 induce necroptosis in respiratory epithelial cells; 2) Does ISG15 modulate necroptotic cell death as well as proinflammatory cytokine/chemokine production in respiratory epithelial cells during SARS-CoV2 infection?; 3) Does necroptosis and its regulation by ISG15 contribute to SARS-CoV2 pathogenesis? Overall, our studies will provide important insight into the pathogenesis of SARS-CoV2 infection and provide potential insight into mechanisms underlying severe disease, which may direct efforts toward the development of diagnostic markers and future countermeasures.",,2024,WASHINGTON UNIVERSITY,236250,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P22777,4U54CA260492-02,Project 1: Mechanisms of innate sensing and pathogenesis of SARS-CoV-2,"Understanding immune responses that contribute to severe COVID-19 is essential to identify patients likely to become critically ill and to discern which pathways to target for therapeutic intervention. The inflammasome is an antiviral and proinflammatory pathway activated by many viruses, but its role in COVID-19 has not been defined fully. Inflammasome activation results in an inflammatory type of cell death called pyroptosis as well as the release of proinflammatory cytokines that include interleukin (IL)-18. Inflammasome cytokines are central to viral control, but excessive or prolonged activation enhances pathogenesis of numerous respiratory virus infections, including avian influenza and SARS-CoV-1. Having extensively studied the role of inflammasome cytokines in the pathogenesis of multiple other viral infections, we measured IL-18 and 36 other cytokines and chemokines in plasma from patients with COVID-19. While most were not significantly different in COVID-19, IL-18 and IL-1 receptor antagonist (RA) levels are elevated in intubated patients with COVID-19 versus non- intubated COVID-19 and hospitalized influenza patients. Incubation of human macrophages with SARS-CoV-2 in vitro produced IL-18, IL-1, IL-RA, IL-6, and IL-8. We used a human macrophage cell-line with various inflammasome genes disrupted to show that caspase-1 and NLRP3 are required for SARS-CoV-2 activation of the inflammasome. We will establish the mechanism by which SARS-CoV-2 activates the inflammasome and determine how inhibition of this pathway alters innate immune signaling using a panel of endocytosis inhibitors, macrophage cell lines with specific inflammasome and other innate sensing genes disrupted, and specific inhibitors of innate sensing in primary human macrophages. Early investigations suggest that antibodies (Abs) modulate innate sensing of SARS-CoV-2. To test whether Abs produced during COVID-19 alter innate signaling, we will incubate SARS-CoV-2 with monoclonal Abs or patient sera, inoculate primary or immortalized macrophages, and measure supernatant cytokines. To investigate cellular function, we developed a flow cytometry-based platform that enables single cell analysis of traditional cell surface markers combined with intracellular staining for proteins involved in metabolic programming. Using this platform, we identified myeloid derived suppressor cells (MDSCs) with distinct metabolic profiles that correlated with severe COVID-19. Prolonged inflammation induces MDSCs in cancer, obesity, and chronic infections. We will use single cell RNA sequencing to characterize these novel MDSCs and assess how cytokines produced in COVID-19 regulate MDSC metabolic programming. The overall goal is to define the mechanism by which SARS-CoV-2 activates inflammatory pathways, Ab modulation, the role of MDSCs, and how they intersect to mediate SARS-CoV-2 immune control and pathology. This will identify targets for therapeutic intervention that minimize inflammatory pathology without impairing antiviral immunity as the foundation of novel clinical trials and markers of disease progression that allow targeting resources to patients most likely to experience severe disease.",,2024,JOHNS HOPKINS UNIVERSITY,302099,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +P22778,1R03AI155950-01,Inflammation and the Treatment of Primary Pneumonic Plague,"Project Summary Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Disease manifests as a rapidly progressing and highly lethal necrotic pneumonia that is typically fatal within seven days. If antibiotic treatment is not administered within 24 hours after the onset of symptoms, pneumonic plague is 100% fatal. Even in the event of appropriate antibiotic therapy, as evidenced in recent outbreaks mortality can still approach 50%. The rapid progression of pneumonic plague and its difficulty to treat highlight a need for improved therapeutic options and a more complete understanding of the host factors driving disease progression. The work proposed here seeks to evaluate the suppression of damaging host immune responses coupled with antibiotic therapy to treat late-stage pneumonic plague. Further, host responses and physiological parameters in the lung are monitored during disease and treatment to understand those conditions that correlate with survival, and those that accompany lethality. The ultimate goals of the proposal are to identify conditions for treatment of late-stage pneumonic plague that favor survivability. This work may have lasting impact on pneumonic plague treatment, as well as severe pneumonia caused by a number of pathogens. The specific aims of the proposal are as follows: Aim 1. Co-treatment with antibiotics and corticosteroids for late-stage pneumonic plague. Preliminary data indicates that pretreating mice with the corticosteroid fluticasone propionate dramatically increases survival after antibiotic treatment of pneumonic plague. Aim 1 seeks to test co-administration of different classes of antibiotics and corticosteroids to treat late-stage pneumonic plague, which is difficult to treat and is highly fatal. This is the first study of its kind that focuses on treatment of disease after symptoms arise. The goal of Aim 1 is to develop an optimal treatment regime for severe and lethal pneumonic plague. Aim 2. Evaluate pulmonary function and innate immune responses during treatment of pneumonic plague. The finding that limiting pulmonary inflammation increases survival in mice offers the opportunity to evaluate host responses under conditions associated with both survivability and lethality. Aim 2 seeks to evaluate host inflammatory responses, immune cell repertoire, and physiological conditions in the lung during disease and treatment of pneumonic plague to identify those conditions that lead to lethality. Further, identifying pulmonary conditions conducive to survival may help to define key metrics and goals for the development of effective therapeutics.",,2022,UNIV OF ARKANSAS FOR MED SCIS,76000,Animals | Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22779,1R01AI153252-01A1,Defining the Role of the Plasminogen Activator Protease in the Early Events that Establish Primary Pneumonic Plague,"Project Summary Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Early after infection, Y. pestis subverts host innate immune mechanisms in the lung and replicates to high numbers before the onset of lethal host inflammatory responses. As a result, pneumonic plague is difficult to treat once symptoms are recognized. This proposal introduces the Yersinia Plasminogen activator protease (Pla) as an important mediator of early host/pathogen interactions in the lung. Pla is well-established virulence factor known to be essential to the pathogenesis of pneumonic plague via an unknown function. The work proposed here examines the dual role of Pla, as both an adhesin and a protease, during pulmonary infection. The objective of this work is to define the function of the critical Yersinia virulence factor Pla in the early events of pneumonic plague to understand how Y. pestis resists clearance by host inflammatory responses to establish an initial replicative phase in the lungs. The strategy for this proposal is outlined below: Specific Aim 1. Define the role of Pla-mediated T3S during pneumonic plague. The adhesin function of Pla facilitates targeting of alveolar macrophages for type 3 secretion (T3S) early during pneumonic plague. Aim 1 will generate and test mutants of Pla to understand how Pla mediates adherence, and characterize the importance of Pla-mediated adherence and T3S in vivo. Further, the impact of Pla-mediated T3S on host cell innate immune responses to T3S will be evaluated during infection to understand how Y. pestis limits host responsiveness early during infection. Specific Aim 2. Characterize novel proteolytic functions of Pla during pneumonic plague. Preliminary data has identified two novel functions of Pla that may contribute to pathogenesis. A proteomics approach will be used to identify and characterize Pla proteolytic activity early during primary pneumonic plague. Specific Aim 3. Identify key host cell types and dynamics responsible for establishing an early pre- inflammatory disease phase during pneumonic plague. Preliminary data indicates that deletion of Pla disrupts the ability of Y. pestis to limit early innate immune responses in the lung. In Aim 3 we will evaluate host cell dynamics and innate immune responses in the lung in the presence and absence of Pla to understand how Y. pestis is able to subvert initial inflammatory responses and establish infection in the lung.",,2026,UNIV OF ARKANSAS FOR MED SCIS,249635,Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2021 +P22780,1F32GM140568-01,Characterizing variation and adaptation in the immune response to plague (Y. pestis) through single-cell sequencing and ancient genomics,"PROJECT SUMMARY Pathogens have been one of the strongest selective pressures in human evolution. Migrating out of Africa, modern humans encountered novel pathogens along with new environments. These populations likely adapted to these pathogens, leading to population-specific adaptations. Consistent with this hypothesis, some of the most compelling signatures of local adaptation in the human genome overlap genes involved in immunity and host defense. Importantly, these regions also overlap genetic loci which are associated with infectious, autoimmune, and inflammatory disease risk in modern humans. Thus, understanding adaptation to pathogens throughout history is important for understanding modern human health. The Black Plague was likely one of the strongest selective events in recent human history. Exposure to Yersinia pestis (the causative agent of plague) therefore likely drove adaptations in the human immune system which continue to shape modern immune variation. Importantly, because the plague ravaged Eurasia while leaving sub-Saharan Africa relatively untouched, adaptation to plague likely occurred in European but not African populations. However, it is not known whether human populations differ in their immune response to plague as a consequence of prior evolutionary history. Addressing this gap is not only important for understanding the recent evolution of the human immune system, but may also help reveal the molecular basis of ancestry-related differences in susceptibility to infectious disease, chronic inflammation, and autoimmune disorders. The basic research questions driving this proposal are: What was the impact of Y. pestis to the functional differentiation of immune responses between African- and European-ancestry individuals? To which extent natural selection has favored the increase in frequency of protective alleles in Europeans, a population with increased exposure to Y. pestis? What cell types and immunological pathways show the most divergence in response to Y. pestis between populations? To answer this questions, I will experimentally infected peripheral blood cells in culture to characterize the immune response to plague. Using single-cell RNA sequencing I will be able to analyze variation in the immune response across cell types, but also characterize differences in the proportion of cells responding to infection and the strength of that response. Using this data, I will identify genes and pathways which are regulated differently in individuals of European and African ancestry, and identify genetic variants which contribute to these differences. I will then use a combination of ancient and modern genomics to test whether loci underlying variation in the immune response to Y. pestis also experienced position selection during the Black Plague. Thus, this project is a novel integration of functional and population genetic approaches to study adaptation to a deadly human pathogen. At its conclusion, this study will reveal how Europeans adapted to Y. pestis exposure during the plague, and identify highly-promising genetic candidates which may contribute to disease susceptibility in modern human populations.",,2024,University Of Chicago,65994,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +P22781,5F31AI147404-02,Identification of a novel zinc acquisition system in Yersinia pestis,"PROJECT SUMMARY Yersinia pestis is the causative agent of human plague. Every year, approximately 2,000 cases of human plague occur, and in the past, several pandemics of plague have caused wide spread population loss. Y. pestis poses a threat to modern society due to its potential to be used as a bioterrorism agent, the absence of a FDA approved vaccine, and the possibility of antibiotic resistance. The identification of novel targets for therapeutic agents is critical for public health and safety. Consequently, Y. pestis is considered a Tier 1 Select Agent. For survival and virulence, Y. pestis must acquire transition metals, such as Fe, Zn, and Mn and overcome nutritional immunity, mechanisms in eukaryotic organisms that restrict nutrients from invading bacteria. During human plague, Yersinia pestis is able to overcome Fe limitation via production of the siderophore Yersiniabactin (Ybt). Recently, we identified an unexpected role for the Ybt system in the ability of Y. pestis to acquire Zn during infection. While the ZnuABC system contributes to in vitro growth in Zn-deficient media, a znu mutant is not attenuated in the mouse model of plague, unless the mutant also lacks genes involved in Ybt synthesis. These data suggest that Y. pestis uses two redundant Zn acquisition systems to cause plague. We hypothesize that Y. pestis produces a novel Ybt synthetase-dependent zincophore required for zinc acquisition and virulence. In Specific Aim 1, we will use a novel Tn-seq method to define genetic elements involved in the zincophore system. Genes that show a Zn phenotype will be validated through growth assays, trans-complementation, and biochemical experiments. In Specific Aim 2, we will determine the contribution of the Ybt synthetase-dependent zinc acquisition system to virulence by utilizing a hemochromatosis mouse model. The hemochromatosis mouse is defective in Fe nutritional immunity, which will allow us to distinguish between the contributions of Ybt synthetase-dependent Fe acquisition and Ybt synthetase-dependent Zn acquisition to Y. pestis virulence. In Specific Aim 3, we will determine the impact of calprotectin on Y. pestis virulence by using in vitro and in vivo methods. Completion of these Aims will define a novel secreted Zn acquisition system in Y. pestis. Our studies will be the first to determine the contribution of Zn acquisition to Y. pestis virulence in the mammalian host and the effect of calprotectin on plague infection. Furthermore, the involvement of conserved Ybt in this novel Zn acquisition demonstrates the significance of these studies to other bacterial pathogens.",,2022,UNIVERSITY OF LOUISVILLE,32561,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies",2020 +P22782,1R01AI148241-01A1,Iron independent role for yersiniabactin in Yersinia pestis,"SUMMARY Transitional metals (e.g., Fe, Zn, Mn) are required by bacteria in order to grow. As such, mammals have a variety of mechanisms to sequester these metals during infection, effectively limiting their availability for use by bacteria (referred to as nutritional immunity). Yersinia pestis, which causes the human disease plague, needed to evolve high-affinity metal acquisition mechanisms to overcome nutritional immunity and colonize its hosts. Because these mechanisms are key to Y. pestis virulence, they represent potential therapeutic targets for the treatment or prevention of plague. Therefore, our long term goals are to identify the mechanisms used by Y. pestis to evade host nutritional immunity and define their roles in virulence. Recently, we have made the exciting discovery that yersiniabactin (Ybt), a siderophore essential for Y. pestis iron (Fe) acquisition, is also able to bind to zinc (Zn), and contributes to Zn acquisition in vitro. Furthermore, using a hemochromatosis mouse model that is defective in Fe-mediated nutritional immunity, we demonstrated for the first time that Ybt contributes to virulence in an Fe-independent manner. Using a Y. pestis mutant defective in Zn acquisition, was also showed that the host protein calprotectin, which is a key component to Zn-mediated nutritional immunity, is a barrier to Y. pestis infection, and Ybt contributes to overcoming this barrier in both pneumonic and bubonic plague. Together, these data are our premise for the conceptually innovative hypothesis that Ybt not only contributes to virulence through Fe acquisition, but also contributes to Zn acquisition, which aids in overcoming calprotectin mediated nutritional immunity. In this proposal, we will build on these exciting discoveries. In Aim 1, we will define the mechanisms that govern metal selectivity of Ybt and the re-acquisition of Ybt-Zn by the bacterium. In Aim 2, we will define the Ybt secretion mechanisms used by Y. pestis and determine the therapeutic potential of inhibiting these secretion systems during plague. Finally, in Aim 3, we will define the role of host calprotectin during plague and the contribution of Ybt to the ability of Y. pestis in overcoming calprotectin mediated Zn sequestration. Importantly, Ybt is a conserved virulence factor in many Gram-negative bacteria. Therefore, the data generated from these studies has the potential to provide us with a broader understanding of the role of Ybt in the virulence of multiple pathogens. Ultimately, these data will provide a foundation for the rational design of new therapeutic approaches targeting these mechanisms to combat Y. pestis infection.",,2026,University Of Louisville,578625,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P22783,1R35GM142939-01,Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA,"PROJECT SUMMARY The possibility of recovering ancient DNA (aDNA) molecules from archeological samples has yielded great opportunities for the study of human evolution and history. Compared to traditional datasets composed of a single time point collected in the present, aDNA allows for the detection of lost genetic lineages and enables the direct assessment of allele frequencies in different time transects. Technologies for obtaining genomic data from archeological material have catapulted the development of the field of paleogenomics, but statistical methods to leverage information from time-series genetic datasets lag behind these technological advances. Over the next five years, the Amorim Lab will develop and apply methods to study human host-pathogen coevolution and adaptation using aDNA. We seek to advance the field of paleogenomics by generating aDNA datasets that comprise large sample sizes per archeological site and developing new methods and approaches to leverage information from time-series genetic data. We will use these novel resources to study host-pathogen interactions during the outbreaks of the plague in Eurasia (e.g. the Black Death) and the period of contact between Indigenous peoples from South America and European colonizers. Contrasting models of population evolution, both analytical and computational, with observed allele frequencies and other summary statistics in different time transects, we will identify the genetic signatures of host-pathogen interactions, characterize the evolutionary processes involved in human response to pathogens, and infer the strength and timing of selective sweeps. In addition, we will characterize the Distribution of Fitness Effects (DFE) of new mutations in the human genome across different time transects and analyze its evolution in light of the environmental shifts caused by disease outbreaks and other events. This study represents an advance over the state-of-the-art knowledge in paleogenomics for its focus on evolutionary process not yet characterized with aDNA (in particular, host-pathogen coevolution), the characterization of the DFE using time-series data, and the development of new resources (datasets and methods). The Amorim Lab is uniquely positioned to accomplish these goals because of our experience in combining model-based approaches with genome data analysis from ancient and modern DNA, as well as our previous experience with the study of medieval Europeans and Native American populations.",,2026,California State University Northridge,352457,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen",2021 +P22784,1R01GM139926-01,Accounting for Hidden Bias in Vaccine Studies: A Negative Control Framework,"Project Summary / Abstract The proposed research aims to develop novel causal inference methods to resolve unmeasured confounding bias known to plague vaccine effectiveness and safety studies by leveraging so-called negative control variables widely available in vaccine studies. A negative control outcome is a variable known not to be causally affected by the treatment of interest, while a negative control exposure is a variable known not to causally affect the outcome of interest. Both share a common confounding mechanism as the exposure-outcome pair of primary interest. Examples of negative controls abound in vaccine studies. Such known-null effects form the basis of falsifica- tion strategy to detect unmeasured confounding, however little is known about when and how negative controls can be used to resolve unmeasured confounding bias. We plan to develop principled negative control methods for identification and semiparametric estimation of causal effects in the presence of unmeasured confounding, incorporating modern highly adaptive machine learning methods. We also plan to develop negative control meth- ods to detect and quantify causal effects in complex longitudinal and survival settings critical to vaccine studies using routinely collected healthcare data. Finally we plan to apply the proposed methods to evaluate vaccine effectiveness using data collected from a pioneering test-negative design platform and to monitor vaccine safety using electronic health record data. Successful completion of the proposed research will equip investigators with paradigm-shifting methods to unlock the full potential of contemporary healthcare data, encourage investigators to routinely check for evidence of confounding bias, and ultimately improve the validity of scientific research.",,2024,University Of Michigan At Ann Arbor,401613,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing | Digital Health,,,United States of America,,"Epidemiological studies | Vaccines research, development and implementation | Health Systems Research",Impact/ effectiveness of control measures | Vaccine trial design and infrastructure | Health information systems,2021 +P22787,1G20AI167410-01,Facility and Building System Upgrades Support for the Howard T. Ricketts Biocontainment Laboratory,"Project Summary/Abstract The Howard Taylor Ricketts Laboratory (HTRL) is a state-of-the-art Regional Biocontainment Laboratory on the Argonne National Laboratory (ANL) campus in DuPage County, Illinois. Located twenty-five miles southwest from the University of Chicago campus, ANL is a federally (Department of Energy) owned site operated by the University of Chicago (UCHICAGO LLC). HTRL is a CDC certified facility owned by the University of Chicago and operated by the Department of Microbiology. Biosafety training and surveillance program involving classroom and laboratory activities ensures that staff, students and fellows comply with state and federal regulations to safely operate facilities and experiments with RG2, RG3 and Select Agent pathogens. The HTRL construction was completed in 2008. Over the last 13 years, the HTRL has hosted research programs studying the bacterial species Yersinia, Brucella, Coxiella, Rickettsia, Bacilli, MRSA and other ESKAPE organisms, as well as viral pathogens including low and highly pathogenic influenza, DENGUE and more recently SARS-CoV2. The facility currently hosts research program on Plague, Anthrax and MRSA, as well as a Core Research Facility for SARS-CoV2. The HTRL is the largest A-BSL3 holding facility in the region and regularly supports research from consortium institutions including UIC, Northwestern U and Loyola U. The HTRL is fulfilling its goal as a biomedical research facility that can rapidly respond to research needs and support biomedical research on emerging and re-emerging pathogens, discovery and testing of new therapeutics and vaccines. The building has been maintained in excellent working conditions and has been in constant use since its construction. However, with the swelling demands for BSL3 and ABSL3 space and research expertise, the development of new technologies for the study of infectious agents, this proposal is a request (i) to upgrade system components necessary to maintain biocontainment, temperature/humidity/pressurization requirements, and safe research operations, and (ii) to replace research equipment that have either outlived the intended useful life or no longer meet facility requirements.",,2024,University Of Chicago,3299716,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22790,1R21AI159706-01,"Bacterial activation and evasion of a PP2A phosphatase â€Â"" Pyrin - Gasdermin D axis","Abstract: Many successful Gram-negative pathogens evade or thwart innate immunity via Type III secretion systems (T3SS), often essential for virulence. Yersinia bacteria cause infections such as gastroenteritis and plague, and is an excellent model system for studies of T3SS effects on innate immune responses. Triggering of inflammasome complexes typically culminate with activation of caspase-1 that then cleaves and matures pro- forms of inflammatory cytokines IL-1b and IL-18, cytokines with well-known antibacterial effects, and the pore- forming and pyroptosis-inducing protein Gasdermin D (GSDMD) at residue D276. GSDMD pores also allow passing of IL-1b/IL-18, but the role of GSDMD cleavage in the resistance to many bacterial infections is poorly understood. We have uncovered an extraordinarily complex set of manipulations of inflammasomes by the Yersinia T3SS. One caspase-1 activation pathway is triggered by Yersinia effector YopE, a RhoA inhibitor, and leads to substantial IL-1b/IL-18 release in myeloid cells via Pyrin inflammasomes. Many details of Pyrin activation remain unclear, but Pyrin does not appear to be directly triggered by toxins or effectors such as YopE or Clostridium TcdB, rather by pathological disturbance of host RhoA signaling. Spontaneously activating alleles of Pyrin are also linked to auto-inflammatory diseases such as familial Mediterranean fever. It is believed that inactive Pyrin is phosphorylated, and an unknown phosphatase is needed to trigger Pyrin inflammasomes. Our experiments suggest PP2A phosphatase is involved. We hypothesize that PP2A phosphatase positively regulates bacterial toxin-induced Pyrin activation leading to cleavage of caspase-1, IL-1b and GSDMD. Furthermore, effective inhibitory mechanisms such as those promoted by Yersinia T3SS effector YopM can block this effective anti-bacterial pathway to promote infection. YopM appears to specifically inhibit the T3SS induced Pyrin inflammasome, likely by interactions with several kinases. Our results suggest that attenuated Yersinia strains lacking YopM regain virulence in the absence of Pyrin or GSDMD. Our goal is to decipher the protective mechanisms against infection mediated by PP2A, Pyrin, caspase-1 and GSDMD but suppressed by YopM, in vitro and in vivo. Our work will bridge the gap of knowledge by clarifying key questions related to how Pyrin is regulated by phosphatases and kinases.",,2023,UNIV OF MASSACHUSETTS MED SCH WORCESTER,251250,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22803,272201700041I-0-759302100227-1,Task A54: Mouse Models for Evaluation of Therapeutics against Human Seasonal Influenza and Avian Influenza Strains with Pandemic Potential,"This contract provides for the development and standardization of small animal models of infectious diseases, and may include efficacy testing of candidate products, including GLP studies to support licensure.",,2022,Utah State University,483208,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +P22804,5K99AI147029-02,Quantifying the genetic and environmental factors driving avian influenza spillover,"PROJECT SUMMARY Past influenza cross-species transmission events have lead to devastating human pandemics. H5N1 is an avian influenza virus that has caused recurrent, high pathogenicity human infections since 1997. Humans usually acquire H5N1 through interaction with live birds, and mounting evidence suggests that H5N1 circulation in poultry is strongly linked to human infection. Despite this, the genetic and environmental factors that promote H5N1 circulation in poultry remain unknown. A predominant hypothesis is that wild birds seed new viruses into poultry, and humans acquire infection via poultry interaction. However, the rate of transmission between wild birds and poultry has never been estimated. Although certain husbandry practices like outdoor rearing and transport to large, live poultry markets are hypothesized to enhance H5N1 circulation, the relative contributions of these husbandry practices have never been systematically assessed. Finally, virologic studies have produced a catalogue of mutations associated with human adaptation in laboratory and animal studies, which are currently used to query emerging H5N1 strains and assess pandemic risk. However, many human-infecting H5N1 strains lack known markers of adaptation, and it is unclear whether these mutations predict spillover risk in nature. In this proposal, I will use phylogenetic and statistical methods to determine the genetic and environmental drivers of H5N1 cross-species transmission through 3 specific aims. Completion of these projects with my mentors and co-mentors will allow me to achieve my career goal of transitioning to an independent faculty role by the end of the K99 phase. 1. I will use a recently developed structured coalescent model to estimate the rate of H5N1 transmission between wild birds, poultry, and humans. I hypothesize that cross-species transmission occurs frequently between wild birds and poultry, but only a small subset of lineages circulate long-term. I expect to observe ongoing transmission in poultry, but not in humans. 2. I will use phylogenetic and statistical methods to determine the environmental and husbandry practices that promote long-term H5N1 circulation in poultry. I hypothesize that short-term spillover events will be associated with outdoor poultry housing and rice cropping. Long-term establishments will be correlated with poor vaccination coverage and introduction into a large poultry market. 3. Elucidate genetic and phenotypic determinants of cross-species transmission. I will combine the power of a genome-wide scan with phenotypic validation to identify the genetic correlates of avian influenza spillover. I hypothesize that H5N1 lineages that are prone to human spillover will be enriched for mutations experimentally linked to host switching. I predict that our scan will identify mutations that elicit improved human receptor binding, enhanced replication in mammalian cells, and abrogation of interferon production.",,2022,FRED HUTCHINSON CANCER RESEARCH CENTER,95010,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease surveillance & mapping",2020 +P22806,1R21AI151418-01A1,Sex-specific Immune Responses to Severe Influenza Virus Infection,"Sex-specific Immune Responses to Severe Influenza Virus Infection ABSTRACT Men and women experience influenza virus infection differently, with women often experiencing a more severe infection. Lung immunopathology is a major contributing factor to influenza virus disease severity and has been linked to differential disease outcomes in men and women. The differences between male and female immune responses during infection are the immune response dynamics, i.e. the speed and magnitude of the reaction of key immune molecules and cells to the virus. These dynamics are regulated by the molecular and cellular interactions that comprise the lung immune system, and it has been shown that lung immune dynamics can be altered in women by altering levels of circulating sex steroids (estradiol) to affect lung inflammation and overall infection severity. Here, we propose an experimental and computational modeling study to quantify the differential immune kinetics that drive the distinct lung immunopathological outcomes observed between men and women. Human male and female infection outcomes have been recapitulated in mouse models. We will infect male and female mice with a moderate pandemic H1N1 virus and a deadly avian influenza virus, collect dynamic immunologic and hormone data, and train mathematical models to the data to quantify the immune kinetics regulating the differential dynamic lung immune responses observed between the sexes. The immunologic data will include major cytokines and immune cells with established significance to virus clearance and respiratory tissue inflammation. Successful completion of the research program will provide the first sex- specific mathematical models of influenza-induced immune responses, the first mathematical models of the avian influenza induced immune response, and the first mathematical models quantifying the impact of sex hormones on lung immune regulation in females. By quantifying which immune kinetics are different between males and females during moderately and severely pathogenic infections, we will generate novel hypotheses on the molecular/cellular origins of lung immunopathology during influenza infection and provide quantitative evidence on whether mechanisms promoting severe lung pathology are dependent on sex, virulence of the virus, or both factors. And quantifying the relationship between sex hormones and lung immune activity in females may provide insight into the mechanisms associated with the increased susceptibility experienced by pregnant women during severe influenza virus infection.",,2022,UNIVERSITY OF PITTSBURGH AT PITTSBURGH,278498,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P22807,5R01AI147497-02,Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine,"ABSTRACT The WHO estimates there are approximately 5 million cases of influenza infections annually, with approximately 500,000 deaths occurring globally. The most cost-effective protection against influenza is vaccination. Unfortunately, due to yearly antigenic shifts and drifts, current seasonal vaccines are ineffective. There is a need for a better flu vaccine. In order to design a better flu vaccine, we plan on optimizing the immune synapse using nano/microparticles (MPs) fabricated from the polymer acetalated dextran (Ac-DEX). Our previous data has shown a dependence of particle degradation and optimal immune response against an influenza antigen. Not only does the release of the antigen effect the immune response, the release of the adjuvant is also important. The optimized degradation of both adjuvant and antigen has a drastic change in survival compared to non- optimized formulations. Our particle system is unique because it relies on the highly tunable polymer Ac-DEX. Ac-DEX is ideal for delivery of agents to phagocytic cells because it is acid-sensitive and has significantly increased degradation in the low acid (~pH 5) of the phagosome. In addition to this it has tunable degradation rates that can range from hours to months, which is a unique range from commonly used polyesters (e.g. poly(lactic-co-glycolic acid) (PLGA)) that have degradation on the order of months. Moreover, Ac-DEX is unique from polyesters because its degradation products are pH neutral, and do not have the potential to shift the local pH or damage sensitive payloads. We have three specific aims exploring various optimizations of our particle system. Aim 1 is focused on formulation of the polymer and particles. The release rate of the adjuvant will be explored. Ac-DEX polymer with various cyclic acetal coverages will be fabricated to degrade over a broad range of times. In Aim 2 we will evaluate the effect of loading of a novel influenza antigen either on the surface or encapsulated into the MPs. We will explore degradation rates on antigen release as well as delivery routes in determining the optimal delivery of influenza antigens that provide a broad range of protection. In Aim 3 we will explore our optimized system in protecting ferrets. Ferrets are the ideal large animal model for influenza infection. Using this model, we will evaluate the vaccine efficacy of our formulation, in comparison to a commercially available flu vaccine.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,578536,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P22808,1R21AI144135-01,Mimicking evolution to define mechanisms of airborne transmission of H7N9 viruses,"The Asian lineage H7N9 avian influenza viruses (AIV) have caused >1500 human zoonotic infections with 615 deaths. These viruses have not spread in humans; however, there is a high potential for these viruses to evolve to transmit via the airborne route and cause a pandemic. Using ferrets, we previously evaluated the ability of the prototypic Asian lineage virus, A/Anhui/1/2013 (H7N9), to undergo two continuous rounds of airborne transmission. In these studies, we found that the virus was able to transmit to 50-66% of respiratory contact ferrets during both rounds of transmission. In a subsequent deep sequence analysis, we identified 2-5 mutations in 90-99% of all variant viruses that transmitted. These mutations were in the hemagglutinin (HA), neuraminidase (NA), and viral polymerase genes. As airborne transmission is associated with enhanced binding and replication in cells of the upper airways, we hypothesize that the identified mutations will alter the molecular properties of the virus to enhance replication in primary human nasal and tracheal epithelial cells. Our aims are: Aim 1. Determine the role of previously identified HA and NA mutations in an H7N9 virus with the A/PR/8 vaccine backbone. Viruses carrying the H7N9 HA and NA on the A/PR8 vaccine backbone will generated. Mutations will be introduced into the HA and NA gene segments and several properties including receptor-binding preference, pH of fusion, thermostability, NA activity, and changes in antibody recognition via immune serum will be evaluated. Aim 2. Evaluate the role of previously identified mutations on the viral polymerase. To assess the impact of mutations in the viral polymerase, in vitro polymerase reconstitution assays will be performed. Specifically, the activity of the wild-type H7N9 polymerase with and without the identified mutations will be assessed. Aim 3. Determine if the introduction of previously identified mutations alters viral replication in primary human airway epithelial cells. To determine if the identified mutations impact viral replication, we will evaluate the replication kinetics of recombinant H7N9-A/PR8 viruses for their growth in primary human airway epithelial cells. Primary human cells will include nasal, tracheal, bronchial, and small airway epithelial cells. Collectively, these studies will determine the effect of the identified mutations on different molecular properties of the virus, while also determining if the mutations alter the viral tropism in human cells. Our findings will generate new insight on how AIV evolve to transmit via the airborne route and will yield critical knowledge required to interpret the evolution and assess the pandemic potential of H7N9 viruses.",,2023,"PENNSYLVANIA STATE UNIVERSITY, THE",226169,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H7,,,,,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P22809,3U45ES006172-29S2,"Promoting Health, Safety, and Recovery Training for COVID-19 Essential Workers and their Communities","Summary/Abstract: Promoting New England Recovery Centers for COVID-19 Essential Workers and Their Communities The New England Consortium-Civil Service Employees Association (TNEC-CSEA) is a worker health and safety training partnership directed by the University of Massachusetts Lowell (UML) based in its Department of Public Health, College of Health Sciences and the UML Climate Change Initiative. TNEC-CSEA delivers open enrollment hazardous waste operations and emergency response (HAZWOPER) related and HAZWOPER supporting trainings and works with diverse groups of public and private sector firms and organizations in the design and delivery of customized contract courses throughout New England and New York State. Consortium partners include four Coalitions for Occupational Safety and Health (COSH organizations: ConnectiCOSH, MassCOSH, NHCOSH, and RICOSH) and the Civil Service Employees Association (CSEA), Local 1000, American Federation of State, County, and Municipal Employees (AFSCME). Since 1987, TNEC has been providing participatory hands-on HAZWOPER training to workers throughout the New England region. In addition to HAZWOPER training, the COSH organizations provide a diversified set of health and safety training programs for labor unions, community organizations, school personnel, and other groups and individuals. CSEA represents 300,000 public sector workers in New York State and has been part of AFSCME’s NIEHS WTP-awarded training program since 2003 and provided substantial direct training from 2007 until joining TNEC. CSEA has built effective internal health and safety management systems through site-specific hands-on training and uses a labor-management cooperative peer-trainer model with 150 active Peer Trainers, 24 of which have been involved for ten or more years, and part of the Emergency Management Operations Protocol to be deployed in emergencies and disasters. TNEC/New England’s previous experience in infectious disease training includes: in 2008-09, delivery of seven 6 to 7 hour Train-the-Trainer courses on avian flu pandemic preparedness to Massachusetts public school teachers, who then delivered training back in their school districts; in 2014, delivery of Ebola-related training to 190 workers including employees of the New Hampshire Department of Public Health, members of the Massachusetts State Police, and leaders of the Massachusetts Nurses Association; and in 2020, CSEA and TNEC/New England developed COVID-19 curricula and trained thousands of workers in New York and the New England states on preventing exposure to SARS-CoV2. TNEC- CSEA proposes to establish two Recovery Centers: a Recovery Center in Connecticut as a partnership between ConnectiCOSH and the Naugatuck Valley Project (based in Waterbury, CT); and a Recovery Center in Massachusetts, led by MassCOSH in partnership with community organizations in East Boston (MassCOSH’s Immigrant Worker Center, GreenRoots, and Neighbors United for Better East Boston), Dorchester (Dorchester Collaborative, a coalition of nine community organizations), Brockton (Brockton Workers Alliance and the Brockton Health Equity Task Force), and New Bedford (Centro Comunitario de Trabajadores).",,2022,UNIVERSITY OF MASSACHUSETTS LOWELL,243004,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",,2021 +P22811,5R03AI148953-02,Calcium transport in Yersinia pestis,"ABSTRACT Pathogenic bacteria, such as Yersinia pestis, are exposed to a wide range of environments within the host and have to be able to adapt to changes in the surrounding environment to establish an infection. One of the most peculiar features of the Y. pestis physiology and virulence is its stringent dependence on alkali/alkaline cations, primarily Ca2+. Despite the importance of calcium in the regulation of Y. pestis virulence factor production, virtually nothing is known about the mechanism of membrane transport of calcium in this organism. In Y. pestis, several different proteins potentially mediate the transport of Ca2+ across the bacterial membrane and some of these proteins are predicted to be able to integrate Ca2+, Na+, and pH homeostasis in this organism. Elucidation of the role of these transport systems in the physiology and ultimately pathogenicity of Y. pestis will allow the assessment of their potential as targets for the development of a novel class of antimicrobials with a completely new mechanism of action.",,2023,Oregon State University,74250,Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22822,5F31AI150114-02,Virus-host interactions underlying species specificity of influenza A virus gene expression,"PROJECT SUMMARY Devastating influenza A virus (IAV) pandemics arise when non-human adapted strains overcome human species barriers to successfully infect and sustain human-to-human transmission. The novelty of a pandemic strain poses a substantial burden to human health leading to increased incidences of severe respiratory complications, hospitalizations, and death when compared to seasonal influenza. The most recent pandemic in 2009 (pH1N1) arose from a reassortant swine IAV that contained human, swine, and avian adapted gene segments. To understand how these pandemic IAVs overcome species barriers, we must understand the mechanisms that lead to viral adaptation to human hosts. Recent work in our lab has demonstrated that regulation of gene expression from the IAV M segment plays a role in host adaptation. The IAV M segment encodes two major proteins by alternative splicing. Matrix 1 (M1) gives the virion its structure and is encoded by the colinear mRNA, and M2, which is needed for viral replication, is encoded by a splice product of the M1 mRNA. We have used reverse genetics to engineer recombinant viruses that share seven of the eight IAV gene segments but differ in the origin of the M segment, allowing us to evaluate properties of this segment. Recombinant viruses carrying avian or human adapted M segments replicate to similar titers and express similar levels of M1 and M2 protein when infecting avian cells. However, in human cells, the avian M segment virus replicates less efficiently and expresses significantly higher levels of M2 mRNA and protein than the human M segment virus. Mammalian adapted M segments maintain low levels of M2 in human cells. These data lead to my hypothesis that, following introduction into mammalian hosts, mutations to the avian IAV M segment are needed to re- establish optimal virus-host interactions important for regulation of M2 expression. In Aim 1, I will map the M sequence determinants that underly differential M gene expression between avian and mammalian adapted M segments. I have used reverse genetics to generate avian M segment viruses that carry nucleotide mutations identified in the pH1N1 M segment. I will infect human cells with these viruses. Then I will evaluate the impact of these mutations on avian and human adapted M1 and M2 mRNA and protein steady state levels and stability. In Aim 2, I will investigate the role of host factors in differential M2 expression between avian and human adapted M segments. I will determine the binding affinities of avian and human M1 mRNAs with host splicing factors using biochemical methods and evaluate subcellular localization of M1 and M2 mRNAs during infection by microscopy. Through these experiments, I will elucidate the molecular mechanisms that underly the species specificity IAV M segment gene expression. These studies will reveal additional mechanisms of IAV adaptation to human hosts, which could be used to better assess the pandemic risks of future IAV zoonoses.",,2023,Emory University,46036,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P22828,1G13LM013554-01,Sickness and Power: The Great North American Epizootic Flu of 1872,"Project Summary The recent outbreak of COVID-19 and the upswing in seasonal influenza this winter offer pressing reminders of the enduring, even intensifying dangers that emergent zoonotic diseasesâ€Â"" disorders caused by pathogens that jump across species dividesâ€Â""pose to human health. Historians of medicine and other scholars have long recognized the power of such diseases to shape human history. Yet few works in epidemiological history have attended to the complicated relationships that continue to link pathogens, humans, other-than-human animals, and the natural and built ecosystems that connect the livesâ€Â""and, often, the deathsâ€Â""of these disparate organisms. This proposal seeks to remedy this gap by supporting the completion of a Geographic Information System (GIS) and scholarly book examining the Great Epizootic Influenza of 1872. This little-known disease event began in Toronto’s market-farming hinterland, where the continuous exchange of pathogens between humans, horses, other farm animals, and wild waterfowl set the stage for the evolution of a new and unprecedentedly virulent form of influenza A virus. Within weeks, swarms of the new virus had engulfed metropolitan Toronto. It took just another month for the disease to spread throughout southeastern Canada and the northeastern U.S. By summer 1873, flu had sickened well over 90% of the horses, mules, and asses in the U.S., Canada, Cuba, Mexico, the Indigenous Nations of the West, and parts of Central America. As it achieved continental proportions, the Great Epizootic prompted economic paralysis, debate about the malady’s nature and treatment, and more than a little soul-searching over human use and misuse of “the noble horse.” Although the disease seemed to dissipate in fall 1873, recent scientific studies strongly suggest that the new flu type responsible for the Great Epizootic lived on and continued to adapt. Descendants of this viral type went on to develop the ability to infect human populations, too, most notably in the Great Pandemic of 1918-’20, a worldwide influenza outbreak that killed at least 50 million people. This proposal supports research in historical documents, the integration of evidence from these primary sources into a Geographic Information System (GIS), and the completion of a scholarly book that casts the Great Epizootic Flu as an unheralded but momentous event in disease history. Employing methodologies and findings from virology, evolutionary ecology, animal behavior, environmental history, and other fields, and adopting a transnational perspective that tracks this outbreak across regional, national, and tribal boundaries, this book offers fresh insights into the past, present, and future of influenza and the many other infectious diseases that don novel configurationsâ€Â""and hence new powers to endanger human and animal health alikeâ€Â""by passing from species to species.",,2024,UNIVERSITY OF COLORADO,49773,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae | Unspecified,Other,,,,,,,,Pandemic-prone influenza | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Secondary impacts of disease, response & control measures",Animal source and routes of transmission | Disease surveillance & mapping | Social impacts | Economic impacts,2021 +P22831,5R01AI153098-02,Triggering germline-encoded broadly neutralizing antibody responses against influenza virus,"Project Summary / Abstract This is an application by Dr. Daniel Lingwood and Dr. Facundo Batista, faculty members of the Ragon Institute of MGH, MIT and Harvard. Both investigators define B cell-antigen recognition principles to inform antibody vaccine design, and for this, have developed two orthogonal transgenic mouse models that recapitulate human antibody responses in vivo. The investigators propose to apply these models to evaluate germline stimulation of human B cell lineages known to give rise to broadly neutralizing antibody (bnAbs) against influenza A viruses (IAV), which account for the majority of flu-hospitalizations and pandemic threats. Most antibody responses to IAV are dominated by off-target, non-neutralizing activities, however, work from the investigators indicates that human BCRs assembled from the antibody VH gene, IGHV1-69, possess natural specificity for a conserved site of vulnerability, the stem-bnAb epitope on the hemagglutinin spike proteins from Group 1 IAV (IAV subtypes: H1, H2, H5, H6, H8, H9, H11, H12, H12, H16). To test if this genetically endows for vaccine- amplifiable bnAb development pathways, the investigators have engineered the LINGWOOD mouse system, where antibodies develop with human antibody VH genes (e.g. IGHV1-69) and full human CDRH3 diversity. Genetic manipulation of this system enables in vivo B cell titration to match the IGHV1-69 B cell frequency found in humans. Sequentially immunizing these mice with SS-np, a nanoparticle displaying the bnAb target, has succeeded in germline stimulation of IGVH1-69 bnAb precursors and IGHV1-69-dependent expansion of bnAb responses; the first example of eliciting high titer IAV bnAbs through vaccination. This response also provided broad protection against Group 1 IAV, including pandemic bird flu, supporting the investigators' central hypothesis that broadly protective bnAbs can be elicited by germline antibody-targeting vaccines. In Aim 1, the investigators will define whether SS-np stands as a universal booster of the IGHV1-69-encoded bnAb response after introduction of B cell memory to diverse IAV `swarms' that simulate human immune history to influenza. In Aim 2, the investigators will define how refocusing serum antibodies against this specific bnAb target also enhances antibody Fc effector functions, potentially co-enabling protection through activation of innate immunity. In Aim 3, the BATISTA mouse system will be used to evaluate vaccine-expansion of IGHV1-69 bnAbs alongside the human IGHV1-18- and IGHV6-1-class bnAb lineages, which neutralize the remaining Group 2 IAV subtypes (H3, H4, H7, H10, H14, H15). In this system, murine IgM B cells bearing individual human bnAb precursors of each pathway are co-transferred to a single recipient mouse. Following immunization, lineage expansions are individually tracked via their progression through B cell germinal centers and then into immune memory. The animals will be co-immunized with SS-np, SS-np2, and SS-np3; three geometrically identical nanoparticles bearing distinct affinities for each bnAb precursor. Selective + collective expansion of these bnAb lineages aims to overcome failure of traditional influenza vaccine approaches.",,2024,MASSACHUSETTS GENERAL HOSPITAL,520617,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H3 | H7 | H10 | Other,,,Unspecified,,,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Vaccine design and administration",2020 +P22834,5R21AI151230-02,Establishing a relevant mouse model with susceptibility to non-adapted influenza viruses for vaccine challenge studies,"SUMMARY Influenza virus infection is a major health concern worldwide. Our best defense against seasonal influenza virus infections is vaccination, but current vaccine strategies are not fully effective and may not offer protection against viruses that emerge from animals. One impediment to the development of better vaccines is the lack of a tractable and cost-effective small animal model for testing new vaccine technology. Mice are ubiquitously used in research, but influenza viruses that infect humans often require adaptation in order to infect and cause pathology in mice. This requirement for virus adaptation limits the utility of the mouse model for testing human vaccine candidates in challenge studies with relevant non-adapated human viruses. However, we found that mice engineered to lack a critical antiviral restriction factor known as interferon-induced transmembrane protein 3 (IFITM3) show increased susceptibility to a variety of influenza virus strains, including human isolates that otherwise do not cause significant pathology in wild type mice. We propose that IFITM3 knockout mice may thus serve as a long-sought mouse model for influenza virus vaccine testing. We will test whether these mice possess the two characteristics needed in a pre-clinical testing model: 1) Whether IFITM3 knockout mice possess the ability to mount protective adaptive immune responses upon vaccination, and 2) Whether IFITM3 knockout mice are fully susceptible to a wide breadth of human and animal-derived influenza viruses. In addition to allowing more rapid and cost-effective testing of new seasonal and universal influenza virus vaccines, this research will also provide insights into humans who possess IFITM3 defects in terms of virus susceptibility and the ability to counteract this immunodeficiency with vaccination.",,2023,Ohio State University,223680,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P22835,5R21AI144433-02,Influenza host specific glycan motif identification through systems biology,"Project Summary Influenza A viruses (IAVs) have caused large losses of life around the world and continue to present a great public health challenge. IAVs can cause infections in birds, sea mammals, lower mammals (e.g., pigs, dogs, and horses), and humans. Previous studies have demonstrated that the structures of the carbohydrate receptors determine influenza host and tissue tropisms. Thus, it is necessary to understand the receptor- binding properties for IAVs and monitor changes to them, especially for IAVs at the animalâ€Â""human interface. However, this understanding is hampered by our lack of detailed knowledge of IAV glycan substructures; most of our knowledge is limited to SA2,3Gal-like and SA2,6Gal-like structures. The goals of this project are to develop and validate a machine learning method to identify host-specific glycan substructures for IAVs by using glycan array data and to identify and validate the glycan motifs associated with the host tropisms of IAVs, including those for zoonotic IAVs. The study will focus on natural hosts of IAVs: humans, swine, canines, equines, and various avian species, including common domestic poultry species and wild bird species. We expect to identify structural determinants for receptor binding with human-, swine-, canine-, and avian-origin IAVs. Such knowledge will help us understand the factors that contribute to influenza infection and transmission and thereby facilitate development of an effective influenza vaccine to prevent virus infection and block virus transmission. This knowledge will also help us develop rapid assays for monitoring emerging influenza threats at the animalâ€Â""human interface. We also expect to develop a computational method for identifying glycan motifs associated with influenza host tropisms; this method will be able to be adapted to determine functional glycan motifs for other proteins, lectins, antibodies, antisera, and microorganisms, including those of other infectious pathogens, by using glycan arrays.",,2022,University Of Missouri-Columbia,199831,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2020 +P22837,1R01AI154656-01A1,Seasonal and universal Vaccination in aged populations with pre-existing immunity,"PROJECT SUMMARY Current influenza (flu) vaccination based on hypervariable hemagglutinin (HA) protein fails to provide effective cross protection. The efficacy of vaccination is low in the aged populations even with pre-existing immunity. The impacts of pre-existing immunity on the immunogenicity and efficacy of universal and seasonal vaccination largely remain not well understood in the aged populations. Development of new flu vaccines and vaccination strategies improving cross protective efficacy in young naïve and aged hosts with pre-existing immunity is of high priority. Mono conserved antigenic targets inducing cross protection tested in naïve animal models include the flu A virus M2 extracellular domain (M2e), HA-stalk domains, and neuraminidase (NA) were reported but insufficient for translation to humans. The multi-target universal vaccines in naïve and aged hosts with pre-existing immunity remain to be developed. We developed heterologous tandem repeat of M2e (5xM2e) presented on immunogenic virus-like particles (5xM2e VLP). Vaccination with 5xM2e VLP was effective in broadening cross protection but suboptimal. A further improved universal vaccine should be developed. Our preliminary studies found synergistic effects on improving cross protection by both M2e and NA immunity. Therefore, as a new universal vaccine candidate, we developed a multi NA + 5xM2e VLP vaccine containing multi-subtype NA and 5xM2e on the same VLP particle. In addition, we newly designed genetically linked novel recombinant M2e-stalk universal protein vaccines effectively inducing both M2e and HA-stalk immunity and conferring broad cross- group protection. Adjuvanted universal vaccination will overcome the aging-related immune senescence by activating T and B immune cells in naïve hosts or aged populations under pre-existing immunity. In this project, we will test the hypothesis that new universal vaccination inducing multi immunity (M2e, Stalk, NA) will enhance the breadth and efficacy of cross protection in adult and aged populations with or without pre-existing immunity. Under Aim 1, we will determine the efficacy of multi-target universal vaccines in young adult mice and ferrets under naïve and pre-existing immune conditions. In Aim 2 studies, we will determine the durability of cross protective immunity by multi targeting new universal vaccines and test a vaccination strategy enhancing cross protection in aged mouse and ferret animal models. In the Aim 3, we will investigate cross protective immune mechanisms of multi targeting universal vaccination in young and aged mouse models. The outcomes in this project will be highly significant in the aspect of translational science and relevance to improve the cross protective efficacy of flu vaccination.",,2026,GEORGIA STATE UNIVERSITY,501999,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies | Characterisation of vaccine-induced immunity,2021 +P22839,3UM1AI148373-02S3,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2022,KAISER FOUNDATION RESEARCH INSTITUTE,1164520,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2021 +P22840,3UM1AI148373-02S2,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2022,KAISER FOUNDATION RESEARCH INSTITUTE,337461,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Therapeutic trial design | Vaccine trial design and infrastructure,2021 +P22841,3UM1AI148373-02S4,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2022,KAISER FOUNDATION RESEARCH INSTITUTE,415583,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2021 +P22843,1R56AI146556-01A1,Determinants of plague susceptibility and resistance,"ABSTRACT Yersinia pestis, the plague agent, caused major pandemics, reiteratively killing most of the human population. The extraordinary mortality of plague is thought to have shaped the human immune system, however its genetic imprint was not known. Y. pestis employs a virulence-plasmid encoded type III secretion system (T3SS) to kill immune cells, thereby replicating unencumbered in the bloodstream of infected hosts. Of particular importance is LcrV, the plague-protective antigen and needle-cap protein of the T3SS, which enables transport of Yersinia effectors (Yops) into immune cells. To identify the human plague receptor for Y. pestis T3SS, we screened for inhibitors that interfere with effector translocation. Ligands of formyl-peptide receptor 1 (FPR1) and antibodies against FPR1 block Y. pestis T3SS injection into human primary neutrophils and cultured immune cells. CRISPR-Cas9 mutagenesis demonstrated that FPR1 is essential for Y. pestis T3SS- mediated killing of human monocytes. Pulldown of tagged FPR1 from Y. pestis infected macrophages revealed the association between FPR1 and T3SS needle complexes, which are comprised of LcrV and YopD. These findings establish FPR1, a G-protein coupled receptor that activates chemotaxis in response to N- formylpeptides or annexin 1 signaling, as the plague receptor on human immune cells. In wild-type mice, plague infection is characterized by Y. pestis T3SS-induced obliteration of the immune system and high mortality, whereas N-formylpeptide receptor deficient (mFpr1-/-) mice exhibit delayed time-to-death, increased survival and the development of protective immunity. Immune cells of mFpr1-/- mice are partially resistant to T3SS and defective for chemotaxis towards Y. pestis. Human FPR1 is a polymorphic gene. Single nucleotide polymorphisms (SNPs) are more frequent in FPR1 than in other human genes. Screening neutrophils of human volunteers for resistance to Y. pestis T3SS, we identified FPR1R190W as a candidate resistance allele. This proposal explores the molecular mechanisms linking Y. pestis T3SS and LcrV with human FPR1 and other host factors to gain deep understanding into the pathogenesis of plague and the mechanisms that shaped FPR1 and human immune responses. Other work will characterize the plague receptor on immune cells of mice, testing the hypothesis that mutations in FPR1 confer resistance to plague disease. N- formylpeptide receptors of different animal species will be characterized to understand plague susceptibility and resistance in mammals.",,2022,University Of Chicago,405000,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22844,5P20GM103625-09,Evaluating Key Steps in the Progression of Pneumonic Plague,"Project Summary/Abstract Pneumonic plague is the deadliest form of disease caused by Yersinia pestis and the basis for its classification as a Tier 1 Select Agent. In the absence of antibiotics mortality rates approach 100% within a week of pulmonary exposure to Y. pestis. The progression of disease begins with an initial “pre-inflammatory” phase in the lung highlighted by a lack of symptoms or detectable host responses. After 36-48 hours there is an abrupt switch into a “pro-inflammatory” phase of disease characterized by the rapid onset of symptoms and the dramatic accumulation of immune infiltrate in the airways. The objective of the work proposed here is to characterize host factors that contribute to the biphasic progression of pneumonic plague by: 1. Identifying mediators of early host/pathogen interactions; 2. Characterizing the role and mechanism of inflammatory damage in the lung during infection; and 3. Targeting lethal host responses to enhance treatment of late-stage disease. Each of these goals will be approached as follows: Identify host mediators of Y. pestis type III secretion (Aim 1): Use a human siRNA library to identify genes that facilitate injection by the type III secretion system. Evaluate host inflammatory damage during the pro-inflammatory disease phase (Aim 2): Determine the role and mechanism of inflammatory damage in the lung during pneumonic plague using inhibitors and mouse lines deficient in key neutrophil-related functions. Optimize treatment for late-stage pneumonic plague (Aim 3): Combine inhibitors of inflammation with antibiotics to optimize treatment during late-stage, lethal pneumonic plague. Characterizing these key steps during disease is essential to fully understanding the pathogenesis of pneumonic plague. This work will yield crucial insight into how dysregulated host inflammatory responses can manifest as severe necrotizing pneumonia.",,-99,UNIV OF ARKANSAS FOR MED SCIS,250791,Bacteria,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22845,1R56AI153524-01,Immunological characterization of rationally-designed vaccines against plague in mice and non-human primate models,"Yersinia pestis (Yp) is the causative agent of bubonic and pneumonic plague. The increasing number of plague cases globally (2010-2017), including the U.S., with a ~18% case fatality rate may reflect climate changes and a rodent carrier range shift. An outbreak of 2017 in Madagascar with ~2400 cases (>75% pneumonic) and ~9% causalities has led WHO (April 2018) to intensify the need for developing new generation subunit and live- attenuated plague vaccines. Yp’s ability to persist in dead hosts, and then resurge after years of silence, is alarming. Also, antibiotic-resistant Yp strains occur naturally or have been intentionally developed and currently no FDA-approved plague vaccine is available. Finally, two-component subunit vaccines composed of capsular antigen F1 and a T3SS component and effector LcrV (low calcium response V antigen), which only generate a humoral immune response, provide variable protection in African green monkeys (AGM) and generate poor T cell-mediate immune responses in humans. Since the cellular immunity is also critical for protection, we focused first on identifying new virulence genes of Yp and then to delete such genes in combination to develop novel live-attenuated vaccine strains. Our data indicated that two such vaccine candidates were 100% attenuated in inducing bubonic/pneumonic plague in mice/rats and generated long-term robust humoral and cellular immune responses to provide 100% protection to rodents against developing pneumonic plague. No clinical symptoms of the disease or histopathological lesions were noted either during immunization or when the vaccinated animals were subsequently exposed to wild-type Yp CO92 in a pneumonic plague model. We hypothesize that further immunological characterization of these mutants and their testing in higher animals, such as cynomolgus macaques (CM) and AGM, will provide a rationale for future preclinical and clinical studies. There is a precedent for using a live-attenuated vaccine against plague, as EV76 strain is used in humans in some parts of the world where plague is endemic. However, the vaccine is reactogenic, represents a spontaneous mutant, and causes disease in patients with over iron load. Three Aims have been proposed: Aim 1, to demonstrate efficacy and immune responses of two vaccine candidates generated from Yp CO92 (biovar Orientalis) against other Yp biovars (Antiqua and Medievalis), and the F1-minus mutant of CO92 in bubonic and pneumonic mouse models. Our data with the mutants indicated a potential role of IL-17 (a Th17 cytokine), Th1-IFN-γ, and antibodies in protection. In Aim 2, we will study the mechanistic basis of this protection (one chosen mutant) by using RORt- /- mice, which lack Th17 cells, as well as IFN-γ, and IgA k/o mice and to discern their links to neutrophil recruitment and mucosal immunity, to combat Yp infection in bubonic/pneumonic plague models. In Aim 3, CM and AGM will be used with one mutant to demonstrate its short- and long-term efficacy in causing bubonic and/or pneumonic plague as well as reactogenicity. The correlates of protective immunity will then be established. These innovative mechanistic/translational approaches will result in effective new generation plague vaccines.",,2021,University Of Texas Med Br Galveston,224539,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2020 +P22846,1R56AI153252-01,Defining the Role of the Plasminogen Activator Protease in the Early Events that Establish Primary Pneumonic Plague,"Project Summary Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Early after infection, Y. pestis subverts host innate immune mechanisms in the lung and replicates to high numbers before the onset of lethal host inflammatory responses. As a result, pneumonic plague is difficult to treat once symptoms are recognized. This proposal introduces the Yersinia Plasminogen activator protease (Pla) as an important mediator of early host/pathogen interactions in the lung. Pla is well-established virulence factor known to be essential to the pathogenesis of pneumonic plague via an unknown function. The work proposed here examines the dual role of Pla, as both an adhesin and a protease, during pulmonary infection. The objective of this work is to define the function of the critical Yersinia virulence factor Pla in the early events of pneumonic plague to understand how Y. pestis resists clearance by host inflammatory responses to establish an initial replicative phase in the lungs. The strategy for this proposal is outlined below: Specific Aim 1. Define the role of Pla-mediated T3S during pneumonic plague. The adhesin function of Pla facilitates targeting of alveolar macrophages for type 3 secretion (T3S) early during pneumonic plague. Aim 1 will generate and test mutants of Pla to understand how Pla mediates adherence, and characterize the importance of Pla-mediated adherence and T3S in vivo. Further, the impact of Pla-mediated T3S on host cell innate immune responses to T3S will be evaluated during infection to understand how Y. pestis limits host responsiveness early during infection. Specific Aim 2. Characterize novel proteolytic functions of Pla during pneumonic plague. Preliminary data has identified two novel functions of Pla that may contribute to pathogenesis. A proteomics approach will be used to identify and characterize Pla proteolytic activity early during primary pneumonic plague. Specific Aim 3. Identify key host cell types and dynamics responsible for establishing an early pre- inflammatory disease phase during pneumonic plague. Preliminary data indicates that deletion of Pla disrupts the ability of Y. pestis to limit early innate immune responses in the lung. In Aim 3 we will evaluate host cell dynamics and innate immune responses in the lung in the presence and absence of Pla to understand how Y. pestis is able to subvert initial inflammatory responses and establish infection in the lung.",,2021,UNIV OF ARKANSAS FOR MED SCIS,374653,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2020 +P22855,1K99AI147029-01A1,Quantifying the genetic and environmental factors driving avian influenza spillover,"PROJECT SUMMARY Past influenza cross-species transmission events have lead to devastating human pandemics. H5N1 is an avian influenza virus that has caused recurrent, high pathogenicity human infections since 1997. Humans usually acquire H5N1 through interaction with live birds, and mounting evidence suggests that H5N1 circulation in poultry is strongly linked to human infection. Despite this, the genetic and environmental factors that promote H5N1 circulation in poultry remain unknown. A predominant hypothesis is that wild birds seed new viruses into poultry, and humans acquire infection via poultry interaction. However, the rate of transmission between wild birds and poultry has never been estimated. Although certain husbandry practices like outdoor rearing and transport to large, live poultry markets are hypothesized to enhance H5N1 circulation, the relative contributions of these husbandry practices have never been systematically assessed. Finally, virologic studies have produced a catalogue of mutations associated with human adaptation in laboratory and animal studies, which are currently used to query emerging H5N1 strains and assess pandemic risk. However, many human-infecting H5N1 strains lack known markers of adaptation, and it is unclear whether these mutations predict spillover risk in nature. In this proposal, I will use phylogenetic and statistical methods to determine the genetic and environmental drivers of H5N1 cross-species transmission through 3 specific aims. Completion of these projects with my mentors and co-mentors will allow me to achieve my career goal of transitioning to an independent faculty role by the end of the K99 phase. 1. I will use a recently developed structured coalescent model to estimate the rate of H5N1 transmission between wild birds, poultry, and humans. I hypothesize that cross-species transmission occurs frequently between wild birds and poultry, but only a small subset of lineages circulate long-term. I expect to observe ongoing transmission in poultry, but not in humans. 2. I will use phylogenetic and statistical methods to determine the environmental and husbandry practices that promote long-term H5N1 circulation in poultry. I hypothesize that short-term spillover events will be associated with outdoor poultry housing and rice cropping. Long-term establishments will be correlated with poor vaccination coverage and introduction into a large poultry market. 3. Elucidate genetic and phenotypic determinants of cross-species transmission. I will combine the power of a genome-wide scan with phenotypic validation to identify the genetic correlates of avian influenza spillover. I hypothesize that H5N1 lineages that are prone to human spillover will be enriched for mutations experimentally linked to host switching. I predict that our scan will identify mutations that elicit improved human receptor binding, enhanced replication in mammalian cells, and abrogation of interferon production.",,2022,FRED HUTCHINSON CANCER RESEARCH CENTER,128574,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2020 +P22856,1R01AI147497-01A1,Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine,"ABSTRACT The WHO estimates there are approximately 5 million cases of influenza infections annually, with approximately 500,000 deaths occurring globally. The most cost-effective protection against influenza is vaccination. Unfortunately, due to yearly antigenic shifts and drifts, current seasonal vaccines are ineffective. There is a need for a better flu vaccine. In order to design a better flu vaccine, we plan on optimizing the immune synapse using nano/microparticles (MPs) fabricated from the polymer acetalated dextran (Ac-DEX). Our previous data has shown a dependence of particle degradation and optimal immune response against an influenza antigen. Not only does the release of the antigen effect the immune response, the release of the adjuvant is also important. The optimized degradation of both adjuvant and antigen has a drastic change in survival compared to non- optimized formulations. Our particle system is unique because it relies on the highly tunable polymer Ac-DEX. Ac-DEX is ideal for delivery of agents to phagocytic cells because it is acid-sensitive and has significantly increased degradation in the low acid (~pH 5) of the phagosome. In addition to this it has tunable degradation rates that can range from hours to months, which is a unique range from commonly used polyesters (e.g. poly(lactic-co-glycolic acid) (PLGA)) that have degradation on the order of months. Moreover, Ac-DEX is unique from polyesters because its degradation products are pH neutral, and do not have the potential to shift the local pH or damage sensitive payloads. We have three specific aims exploring various optimizations of our particle system. Aim 1 is focused on formulation of the polymer and particles. The release rate of the adjuvant will be explored. Ac-DEX polymer with various cyclic acetal coverages will be fabricated to degrade over a broad range of times. In Aim 2 we will evaluate the effect of loading of a novel influenza antigen either on the surface or encapsulated into the MPs. We will explore degradation rates on antigen release as well as delivery routes in determining the optimal delivery of influenza antigens that provide a broad range of protection. In Aim 3 we will explore our optimized system in protecting ferrets. Ferrets are the ideal large animal model for influenza infection. Using this model, we will evaluate the vaccine efficacy of our formulation, in comparison to a commercially available flu vaccine.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,604292,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P22858,1R03AI148953-01,Calcium transport in Yersinia pestis,"ABSTRACT Pathogenic bacteria, such as Yersinia pestis, are exposed to a wide range of environments within the host and have to be able to adapt to changes in the surrounding environment to establish an infection. One of the most peculiar features of the Y. pestis physiology and virulence is its stringent dependence on alkali/alkaline cations, primarily Ca2+. Despite the importance of calcium in the regulation of Y. pestis virulence factor production, virtually nothing is known about the mechanism of membrane transport of calcium in this organism. In Y. pestis, several different proteins potentially mediate the transport of Ca2+ across the bacterial membrane and some of these proteins are predicted to be able to integrate Ca2+, Na+, and pH homeostasis in this organism. Elucidation of the role of these transport systems in the physiology and ultimately pathogenicity of Y. pestis will allow the assessment of their potential as targets for the development of a novel class of antimicrobials with a completely new mechanism of action.",,2022,Oregon State University,74084,Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P22863,1F31AI150114-01A1,Virus-host interactions underlying species specificity of influenza A virus gene expression,"PROJECT SUMMARY Devastating influenza A virus (IAV) pandemics arise when non-human adapted strains overcome human species barriers to successfully infect and sustain human-to-human transmission. The novelty of a pandemic strain poses a substantial burden to human health leading to increased incidences of severe respiratory complications, hospitalizations, and death when compared to seasonal influenza. The most recent pandemic in 2009 (pH1N1) arose from a reassortant swine IAV that contained human, swine, and avian adapted gene segments. To understand how these pandemic IAVs overcome species barriers, we must understand the mechanisms that lead to viral adaptation to human hosts. Recent work in our lab has demonstrated that regulation of gene expression from the IAV M segment plays a role in host adaptation. The IAV M segment encodes two major proteins by alternative splicing. Matrix 1 (M1) gives the virion its structure and is encoded by the colinear mRNA, and M2, which is needed for viral replication, is encoded by a splice product of the M1 mRNA. We have used reverse genetics to engineer recombinant viruses that share seven of the eight IAV gene segments but differ in the origin of the M segment, allowing us to evaluate properties of this segment. Recombinant viruses carrying avian or human adapted M segments replicate to similar titers and express similar levels of M1 and M2 protein when infecting avian cells. However, in human cells, the avian M segment virus replicates less efficiently and expresses significantly higher levels of M2 mRNA and protein than the human M segment virus. Mammalian adapted M segments maintain low levels of M2 in human cells. These data lead to my hypothesis that, following introduction into mammalian hosts, mutations to the avian IAV M segment are needed to re- establish optimal virus-host interactions important for regulation of M2 expression. In Aim 1, I will map the M sequence determinants that underly differential M gene expression between avian and mammalian adapted M segments. I have used reverse genetics to generate avian M segment viruses that carry nucleotide mutations identified in the pH1N1 M segment. I will infect human cells with these viruses. Then I will evaluate the impact of these mutations on avian and human adapted M1 and M2 mRNA and protein steady state levels and stability. In Aim 2, I will investigate the role of host factors in differential M2 expression between avian and human adapted M segments. I will determine the binding affinities of avian and human M1 mRNAs with host splicing factors using biochemical methods and evaluate subcellular localization of M1 and M2 mRNAs during infection by microscopy. Through these experiments, I will elucidate the molecular mechanisms that underly the species specificity IAV M segment gene expression. These studies will reveal additional mechanisms of IAV adaptation to human hosts, which could be used to better assess the pandemic risks of future IAV zoonoses.",,2023,Emory University,45520,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P22864,1R21AI151230-01,Establishing a relevant mouse model with susceptibility to non-adapted influenza viruses for vaccine challenge studies,"SUMMARY Influenza virus infection is a major health concern worldwide. Our best defense against seasonal influenza virus infections is vaccination, but current vaccine strategies are not fully effective and may not offer protection against viruses that emerge from animals. One impediment to the development of better vaccines is the lack of a tractable and cost-effective small animal model for testing new vaccine technology. Mice are ubiquitously used in research, but influenza viruses that infect humans often require adaptation in order to infect and cause pathology in mice. This requirement for virus adaptation limits the utility of the mouse model for testing human vaccine candidates in challenge studies with relevant non-adapated human viruses. However, we found that mice engineered to lack a critical antiviral restriction factor known as interferon-induced transmembrane protein 3 (IFITM3) show increased susceptibility to a variety of influenza virus strains, including human isolates that otherwise do not cause significant pathology in wild type mice. We propose that IFITM3 knockout mice may thus serve as a long-sought mouse model for influenza virus vaccine testing. We will test whether these mice possess the two characteristics needed in a pre-clinical testing model: 1) Whether IFITM3 knockout mice possess the ability to mount protective adaptive immune responses upon vaccination, and 2) Whether IFITM3 knockout mice are fully susceptible to a wide breadth of human and animal-derived influenza viruses. In addition to allowing more rapid and cost-effective testing of new seasonal and universal influenza virus vaccines, this research will also provide insights into humans who possess IFITM3 defects in terms of virus susceptibility and the ability to counteract this immunodeficiency with vaccination.",,2022,Ohio State University,185264,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P22865,1R01AI153098-01,Triggering germline-encoded broadly neutralizing antibody responses against influenza virus,"Project Summary / Abstract This is an application by Dr. Daniel Lingwood and Dr. Facundo Batista, faculty members of the Ragon Institute of MGH, MIT and Harvard. Both investigators define B cell-antigen recognition principles to inform antibody vaccine design, and for this, have developed two orthogonal transgenic mouse models that recapitulate human antibody responses in vivo. The investigators propose to apply these models to evaluate germline stimulation of human B cell lineages known to give rise to broadly neutralizing antibody (bnAbs) against influenza A viruses (IAV), which account for the majority of flu-hospitalizations and pandemic threats. Most antibody responses to IAV are dominated by off-target, non-neutralizing activities, however, work from the investigators indicates that human BCRs assembled from the antibody VH gene, IGHV1-69, possess natural specificity for a conserved site of vulnerability, the stem-bnAb epitope on the hemagglutinin spike proteins from Group 1 IAV (IAV subtypes: H1, H2, H5, H6, H8, H9, H11, H12, H12, H16). To test if this genetically endows for vaccine- amplifiable bnAb development pathways, the investigators have engineered the LINGWOOD mouse system, where antibodies develop with human antibody VH genes (e.g. IGHV1-69) and full human CDRH3 diversity. Genetic manipulation of this system enables in vivo B cell titration to match the IGHV1-69 B cell frequency found in humans. Sequentially immunizing these mice with SS-np, a nanoparticle displaying the bnAb target, has succeeded in germline stimulation of IGVH1-69 bnAb precursors and IGHV1-69-dependent expansion of bnAb responses; the first example of eliciting high titer IAV bnAbs through vaccination. This response also provided broad protection against Group 1 IAV, including pandemic bird flu, supporting the investigators' central hypothesis that broadly protective bnAbs can be elicited by germline antibody-targeting vaccines. In Aim 1, the investigators will define whether SS-np stands as a universal booster of the IGHV1-69-encoded bnAb response after introduction of B cell memory to diverse IAV `swarms' that simulate human immune history to influenza. In Aim 2, the investigators will define how refocusing serum antibodies against this specific bnAb target also enhances antibody Fc effector functions, potentially co-enabling protection through activation of innate immunity. In Aim 3, the BATISTA mouse system will be used to evaluate vaccine-expansion of IGHV1-69 bnAbs alongside the human IGHV1-18- and IGHV6-1-class bnAb lineages, which neutralize the remaining Group 2 IAV subtypes (H3, H4, H7, H10, H14, H15). In this system, murine IgM B cells bearing individual human bnAb precursors of each pathway are co-transferred to a single recipient mouse. Following immunization, lineage expansions are individually tracked via their progression through B cell germinal centers and then into immune memory. The animals will be co-immunized with SS-np, SS-np2, and SS-np3; three geometrically identical nanoparticles bearing distinct affinities for each bnAb precursor. Selective + collective expansion of these bnAb lineages aims to overcome failure of traditional influenza vaccine approaches.",,2024,MASSACHUSETTS GENERAL HOSPITAL,520617,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H3 | H7 | H10 | Other,,,Unspecified,,,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Vaccine design and administration",2020 +P22867,1R21AI144433-01A1,Influenza host specific glycan motif identification through systems biology,"Project Summary Influenza A viruses (IAVs) have caused large losses of life around the world and continue to present a great public health challenge. IAVs can cause infections in birds, sea mammals, lower mammals (e.g., pigs, dogs, and horses), and humans. Previous studies have demonstrated that the structures of the carbohydrate receptors determine influenza host and tissue tropisms. Thus, it is necessary to understand the receptor- binding properties for IAVs and monitor changes to them, especially for IAVs at the animalâ€Â""human interface. However, this understanding is hampered by our lack of detailed knowledge of IAV glycan substructures; most of our knowledge is limited to SA2,3Gal-like and SA2,6Gal-like structures. The goals of this project are to develop and validate a machine learning method to identify host-specific glycan substructures for IAVs by using glycan array data and to identify and validate the glycan motifs associated with the host tropisms of IAVs, including those for zoonotic IAVs. The study will focus on natural hosts of IAVs: humans, swine, canines, equines, and various avian species, including common domestic poultry species and wild bird species. We expect to identify structural determinants for receptor binding with human-, swine-, canine-, and avian-origin IAVs. Such knowledge will help us understand the factors that contribute to influenza infection and transmission and thereby facilitate development of an effective influenza vaccine to prevent virus infection and block virus transmission. This knowledge will also help us develop rapid assays for monitoring emerging influenza threats at the animalâ€Â""human interface. We also expect to develop a computational method for identifying glycan motifs associated with influenza host tropisms; this method will be able to be adapted to determine functional glycan motifs for other proteins, lectins, antibodies, antisera, and microorganisms, including those of other infectious pathogens, by using glycan arrays.",,2021,University Of Missouri-Columbia,239725,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2020 +P22871,3UM1AI148373-01S2,Kaiser Washington VTEU supplement 20-0003,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2022,KAISER FOUNDATION RESEARCH INSTITUTE,7505188,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2020 +P22872,3UM1AI148373-01S1,Kaiser Washington Vaccine and Treatment Evaluation Unit,"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance.",,2021,KAISER FOUNDATION RESEARCH INSTITUTE,1884389,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine logistics and supply chains and distribution strategies,2020 +P22873,1U54CA260492-01,Project 1: Mechanisms of innate sensing and pathogenesis of SARS-CoV-2,"Understanding immune responses that contribute to severe COVID-19 is essential to identify patients likely to become critically ill and to discern which pathways to target for therapeutic intervention. The inflammasome is an antiviral and proinflammatory pathway activated by many viruses, but its role in COVID-19 has not been defined fully. Inflammasome activation results in an inflammatory type of cell death called pyroptosis as well as the release of proinflammatory cytokines that include interleukin (IL)-18. Inflammasome cytokines are central to viral control, but excessive or prolonged activation enhances pathogenesis of numerous respiratory virus infections, including avian influenza and SARS-CoV-1. Having extensively studied the role of inflammasome cytokines in the pathogenesis of multiple other viral infections, we measured IL-18 and 36 other cytokines and chemokines in plasma from patients with COVID-19. While most were not significantly different in COVID-19, IL-18 and IL-1 receptor antagonist (RA) levels are elevated in intubated patients with COVID-19 versus non- intubated COVID-19 and hospitalized influenza patients. Incubation of human macrophages with SARS-CoV-2 in vitro produced IL-18, IL-1, IL-RA, IL-6, and IL-8. We used a human macrophage cell-line with various inflammasome genes disrupted to show that caspase-1 and NLRP3 are required for SARS-CoV-2 activation of the inflammasome. We will establish the mechanism by which SARS-CoV-2 activates the inflammasome and determine how inhibition of this pathway alters innate immune signaling using a panel of endocytosis inhibitors, macrophage cell lines with specific inflammasome and other innate sensing genes disrupted, and specific inhibitors of innate sensing in primary human macrophages. Early investigations suggest that antibodies (Abs) modulate innate sensing of SARS-CoV-2. To test whether Abs produced during COVID-19 alter innate signaling, we will incubate SARS-CoV-2 with monoclonal Abs or patient sera, inoculate primary or immortalized macrophages, and measure supernatant cytokines. To investigate cellular function, we developed a flow cytometry-based platform that enables single cell analysis of traditional cell surface markers combined with intracellular staining for proteins involved in metabolic programming. Using this platform, we identified myeloid derived suppressor cells (MDSCs) with distinct metabolic profiles that correlated with severe COVID-19. Prolonged inflammation induces MDSCs in cancer, obesity, and chronic infections. We will use single cell RNA sequencing to characterize these novel MDSCs and assess how cytokines produced in COVID-19 regulate MDSC metabolic programming. The overall goal is to define the mechanism by which SARS-CoV-2 activates inflammatory pathways, Ab modulation, the role of MDSCs, and how they intersect to mediate SARS-CoV-2 immune control and pathology. This will identify targets for therapeutic intervention that minimize inflammatory pathology without impairing antiviral immunity as the foundation of novel clinical trials and markers of disease progression that allow targeting resources to patients most likely to experience severe disease.",,2022,JOHNS HOPKINS UNIVERSITY,815251,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +P22874,1F31AI147404-01,Identification of a novel zinc acquisition system in Yersinia pestis,"PROJECT SUMMARY Yersinia pestis is the causative agent of human plague. Every year, approximately 2,000 cases of human plague occur, and in the past, several pandemics of plague have caused wide spread population loss. Y. pestis poses a threat to modern society due to its potential to be used as a bioterrorism agent, the absence of a FDA approved vaccine, and the possibility of antibiotic resistance. The identification of novel targets for therapeutic agents is critical for public health and safety. Consequently, Y. pestis is considered a Tier 1 Select Agent. For survival and virulence, Y. pestis must acquire transition metals, such as Fe, Zn, and Mn and overcome nutritional immunity, mechanisms in eukaryotic organisms that restrict nutrients from invading bacteria. During human plague, Yersinia pestis is able to overcome Fe limitation via production of the siderophore Yersiniabactin (Ybt). Recently, we identified an unexpected role for the Ybt system in the ability of Y. pestis to acquire Zn during infection. While the ZnuABC system contributes to in vitro growth in Zn-deficient media, a znu mutant is not attenuated in the mouse model of plague, unless the mutant also lacks genes involved in Ybt synthesis. These data suggest that Y. pestis uses two redundant Zn acquisition systems to cause plague. We hypothesize that Y. pestis produces a novel Ybt synthetase-dependent zincophore required for zinc acquisition and virulence. In Specific Aim 1, we will use a novel Tn-seq method to define genetic elements involved in the zincophore system. Genes that show a Zn phenotype will be validated through growth assays, trans-complementation, and biochemical experiments. In Specific Aim 2, we will determine the contribution of the Ybt synthetase-dependent zinc acquisition system to virulence by utilizing a hemochromatosis mouse model. The hemochromatosis mouse is defective in Fe nutritional immunity, which will allow us to distinguish between the contributions of Ybt synthetase-dependent Fe acquisition and Ybt synthetase-dependent Zn acquisition to Y. pestis virulence. In Specific Aim 3, we will determine the impact of calprotectin on Y. pestis virulence by using in vitro and in vivo methods. Completion of these Aims will define a novel secreted Zn acquisition system in Y. pestis. Our studies will be the first to determine the contribution of Zn acquisition to Y. pestis virulence in the mammalian host and the effect of calprotectin on plague infection. Furthermore, the involvement of conserved Ybt in this novel Zn acquisition demonstrates the significance of these studies to other bacterial pathogens.",,2022,UNIVERSITY OF LOUISVILLE,31468,Bacteria,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2020 +P22875,1R35GM152007-01,Mechanistic bases of strain-specific virus-host interactions,"Abstract Influenza A viruses (IAVs) are responsible for seasonal flu and pose a pandemic threat. The overarching goal of our research is to understand the structural and biophysical mechanisms at the molecular level by which nonstructural protein 1 (NS1) of IAVs interferes with host antiviral responses. NS1 is a major virulence factor of IAVs, counteracting host antiviral immune responses. Remarkably, NS1 has a multifaceted strategy to interfere with many host proteins involved in viral RNA (vRNA) sensing and degradation, apoptosis, and interferon production. Furthermore, NS1 is one of the most frequently mutating proteins in the IAV genome. Therefore, studying the evolution of NS1 and its role in immune evasion and modulation is essential for understanding the strain-specific virulence of IAVs. However, to understand the evolutionary development of NS1’s strain-specific functions, it is necessary to examine the interactions between newly acquired mutations and other residues within NS1, which are known as epistatic interactions. Addressing the molecular mechanisms of epistasis is a major challenge in the fields of protein science and evolution. Over the next five years, we will investigate how NS1 interferes with host immune responses in a strain-specific manner. In this proposed research, we will address the questions of how epistatic interactions contribute to the strain-specific interactions between NS1 and host proteins, and how NS1 employs its RNA-binding ability to antagonize vRNA sensors that initiate innate immune responses. To accomplish our goal, we will use an integrated approach including X-ray crystallography, cryo-electron microscopy (EM), NMR and fluorescence spectroscopies, chemical crosslinking using amber-codon suppression, molecular dynamics simulation, and cell-based experiments to parallel our structural and biophysical studies. This research will provide a mechanistic framework for a quantitative understanding of NS1's strain-specific immune evasion functions. As a result, this study is expected to have a positive impact on the development of antiviral agents targeting NS1-host protein interactions.",,2029,TEXAS A&M AGRILIFE RESEARCH,364316,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2024 +P22876,5F31HL164049-02,Duration and Function of Lung Tissue Resident CD8+ Memory T cells,"PROJECT SUMMARY/ABSTRACT Influenza is a respiratory virus that infects an estimated one billion people around the world annually. While there is an influenza vaccine, it is typically only 40-60% effective and people must receive it every year. Additionally, the vaccine does not protect against future, and possibly pandemic, strains of influenza and thus there is a major need for new vaccination strategies. CD8+ T cells can provide cross protection against different strains of influenza because they recognize internal epitopes that are conserved. Specifically, due to their position in the lung, CD8+ tissue resident memory T cells (TRM) can rapidly respond to infection and mediate protection by reducing viral loads and immunopathology. In mice, studies have shown that influenza-specific CD8+ lung TRM have limited durability, but it is unknown how long lung TRM survive in humans. Additionally, the mechanisms by which lung TRM cytokines reduce viral loads and immunopathology is unknown in mice, and even less is known about the function of lung TRM in humans. Here, we propose a series of experiments to fill these critical gaps in knowledge. In Aim 1, we will use longitudinal bronchoalveolar lavage samples from lung transplant patients and antibodies specific for mismatched HLA alleles between recipient and donor to track the duration of donor lung TRM and the development of recipient lung TRM by flow cytometry. Additionally, we will determine the dynamics of flu-specific human lung TRM by performing immunophenotyping on longitudinal bronchoalveolar lavage, blood, and nasal lavage samples from lung transplant patients that become infected with influenza. In Aim 2, we will obtain healthy lungs that are unable to be transplanted in order to examine the effector functions of human lung TRM. Lung cells will be stimulated with influenza peptide pools to determine the cytokines produced by influenza- specific lung TRM, and the impact those cytokines have on neighboring cells in the lung tissue. Additionally, we will then use mice to mechanistically determine the effect of individual lung TRM cytokines to reduce viral loads and activate neighboring innate cells. Through this proposed work we hope to better understand the role that human lung TRM play in the immune response to influenza. Lastly, as lung TRM are generated in response to respiratory viruses, and not just influenza, results of this study could provide insights into the immune system that could improve vaccine design for all respiratory viruses and aid in the prevention of future global pandemics.",,2025,EMORY UNIVERSITY,47694,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P22877,5R21AI173593-02,Harnessing Age-Associated B cells for a Universal Influenza Vaccine for the Aged,"ABSTRACT: Harnessing Age-Associated B Cells for a Universal Influenza Vaccine for the Aged. With age, the generation of T follicular helpers from naive CD4 T cells, and germinal center B cells from follicular B cells, that are both needed for the generation of high affinity antibody (Ab), become highly compromised. Most current vaccines for influenza in the elderly are not effective at inducing these critical responses. Thus, the elderly, though protected by Ab already in place for pathogens encountered earlier in life, are highly susceptible to new strains of virus (e.g. influenza) and newly emerged pathogens (e.g. pandemic influenzas, COVID-19). We described the generation of an unusual population of Ab-secreting B cells that developed to live influenza infection in aged mice. We found they were derived from stimulation of recently described ""age-associated B cells"" (ABC) of a naïve sIgD+ phenotype. In the aged, these influenza-induced ABC (iABC) are generated independently of CD4 T cell help, but strictly depend on stimulation by pathogen-associated ""danger"" signals and thus they are generated well in aged infected mice. Notably, ABC are the predominant naïve B cells that respond in aged mice. Here we will determine the potential of IgD ABC to respond to influenza infection and generate Ab-secreting cells (AbSC) effector iABC that are either recirculating or are tissue resident. We will determine if they give rise to B cell memory, both resting memory and long-lived Ab-secreting cells, and if these are found in the lower respiratory tract (lung) and upper respiratory tract (URT):nasal tissues and nasal associated lymphoid tissue- NALT), as well as the spleen and BM. We will determine the contribution of ABC-derived effector and memory subsets and the Ab they produce in these the different sites to protection from reinfection. We will ask how long- lived are the memory cells in distinct sites. We will compare the ability of live influenza virus, whole inactivated virus, and mRNA-LNP HA vaccine to generate the recirculating and tissue resident effector and memory subsets and to induce protective immunity. These results will give us new insights into this novel age-associated immune pathway and give us important new insights into whether harnessing the aged ABC response can provide superior protection in the aged. It will provide indications of what general vaccine strategies are likely to be needed to immunize the ABC in the elderly. These findings could lead to a more Universal vaccines that can provide robust protection to the elderly, who are currently highly vulnerable.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,188438,Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22879,1K08HL171895-01,The Role of E3 Ligase MARCH10 in Influenza Virus Infection,"PROJECT SUMMARY There are ~1 billion human influenza cases worldwide each year, resulting in up to 650,000 deaths. Influenza virus infects cells of the airways and distal lung, causing acute lung injury. The main class of antiviral drugs recommended for treating influenza works by blocking the viral neuraminidase enzyme on the virus surface to prevent the release of viral particles from infected cells. However, the increasing emergence of drug resistance limits their effectiveness. Therefore, there is an urgent need to identify novel molecular regulators and pathways of the innate immune response in the lung against influenza virus infection. This proposal is driven by our novel finding that the E3 ubiquitin ligase MARCH10, a protein never described in the lungs in the context of influenza virus infection with no known role in pulmonary immunity, is significantly downregulated by influenza virus infection in human and murine lungs. Overexpression of MARCH10 also drastically decreases the viral protein influenza hemagglutinin when lung epithelial cells are infected with influenza virus. We hypothesize that MARCH10, regulated at the transcriptional level, decreases influenza pathogenesis and is a critical regulator of airway epithelial cell host defense. We have proposed the following specific aims to investigate this hypothesis: 1) Determine if influenza virus induces a stage-specific decrease in MARCH10 at the gene transcriptional level and 2) Determine if catalytically active MARCH10 reduces influenza virus pathogenesis via post-transcriptional mechanisms. To accomplish these goals, the principal investigator has developed a five-year training program under the guidance of her mentors, Dr. Rama Mallampalli â€Â"" an expert in ubiquitin-mediated proteolysis and acute lung injury and Dr. Jacob Yount - an expert in influenza and viral immunology, to acquire training in advanced molecular and cell biology techniques, virology techniques, and small animal model development. The candidate’s training will also be overseen by a Scientific Advisory Committee to lend expertise, provide oversight and evaluate progress, including, Dr. Mallampalli, Dr. Yount, Dr. Estelle Cormet-Boyaka â€Â"" an expert in lung epithelial cell biology, and Dr. Dan Wozniak â€Â"" an expert in lung and bacterial pathogenesis. The proposed career development plan will provide the additional training necessary to achieve the principal investigator’s ultimate goal of becoming an independent physician-scientist studying the biological mechanisms by which lung epithelial cells respond to respiratory viral infections and modulate the lung innate immune response and translate these findings into novel therapeutics to prevent and treat viral infections and its associated lung injury.",,2028,Ohio State University,165024,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2024 +P22883,5U01IP001136-04,"RFA-IP-22-004, Modeling toolkit to evaluate multifaceted control strategies for seasonal and pandemic influenza","PROJECT SUMMARY We will develop a data-driven model of seasonal and pandemic influenza transmission throughout the US to accelerate robust assessments of multifaceted influenza intervention strategies. We will work closely with the CDC Modeling Network to advance the fidelity, transparency and translation of models as an evidence base for influenza policy making, prevention and control. This project extends a metapopulation model of influenza transmission within and between 217 major metropolitan areas in the US that we are developing in collaboration with the CDC Modeling Network. The model includes travel between cities, age- and risk-group specific susceptibility, probability of clinical outcomes, intervention efficacies and uptake rates, as well as the impacts of local climate and school calendars on transmission rates. Using a range of public health, epidemiological, societal and economic metrics, the model can flexibly evaluate thousands of candidate intervention strategies, including time- and location-based combinations of vaccines, antivirals, and social distancing measures with potential subgroup-specific prioritization. Our proposal includes four major aims. In Aim 1, we will extend our US Influenza Model to include the co- circulation of multiple viruses competing via transient heterosubtypic immunity. We will derive new estimates for the duration and magnitude of heterosubtypic immunity and design strain-specific strategies for effectively controlling co-circulating seasonal and pandemic influenza viruses. In Aim 2, we will evaluate intervention strategies that leverage newly approved and combined antiviral drugs. We will fit within-host viral dynamic models to clinical data on new antivirals to estimate the efficacy of various drug regimens in different subpopulations with respect to disease severity, infectiousness, and the risk of antiviral resistance. In Aim 3, we will build a granular within-city model of influenza transmission based on abundant data and local collaborations with public health and healthcare leaders in the Austin-Round Rock Metropolitan Area. We will apply the model to elucidate socioeconomic and geographic disparities in influenza risk and design interventions that ameliorate such gaps. In Aim 4, we will build an interactive visualization platform that allows users to specify epidemic scenarios, implement layered interventions as simulations unfold, and view the model dynamics through the lens of a surveillance module based on the CDC’s FluView Interactive portal. We will work extensively with the CDC Modeling Network to build a diverse portfolio of validated models and best practices for collaborative decision support. Our projects will contribute flexible models for the evaluation of multifaceted influenza interventions, elucidate competition among influenza viruses and the efficacies of novel antivirals, and provide insights into socioeconomic disparities in influenza burden. Furthermore, our innovative visualization tool will broadly support the translation of science to public policy.",,2025,University Of Texas At Austin,738731,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing | Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Disease models | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2020 +P22884,5U01IP001141-04,Individual-based Simulation of Seasonal and Pandemic Influenza Epidemics - supplement Emergency Response to the COVID-19 Pandemic,"Project Abstract Seasonal influenza caused an estimated 48.8 million illnesses, 22.7 million health care visits, 959,000 hospitalizations, and 79,400 deaths in 2017-18. Influenza is a particularly complicated disease to prevent as the influenza virus itself changes over time, and unlike vaccinations for measles or hepatitis B, the effectiveness of annual vaccination may be limited if the particular strain that appears in an outbreak is not represented in the vaccine. In addition, the immunity produced by vaccination declines over time, and many individuals, especially the elderly, may lose protection toward the end of an influenza season. The goals of iMPH: Influenza Modeling for Public Health are to bring together four experienced modeling groups including the Public Health Dynamics Laboratory (PHDL) that has significant experience as a MIDAS Center of Excellence in the agent-based modeling of influenza, the Pittsburgh Vaccine Research Group (PittVax), vaccine policy experts who are site leads in both the inpatient and outpatient CDC influenza vaccine effectiveness (VE) networks, the DELPHI (Developing the Theory and Practice of Epidemiological Forecasting) group at CMU, the most accurate US influenza prediction group, and the current MIDAS Network Coordination Center (MCC) that brings major data and model coordination expertise. Our specific Aims are to create realistic, biologically based models of influenza, including the development and maintenance of immunity over time through either the development of the disease or vaccination so that we can test the benefit of different prevention strategies in seasonal or pandemic influenza. Specifically, we will examine strategies such as: enhanced vaccines that create high initial antibody levels, the addition of a second, mid-season vaccine, or potentially delaying vaccination in some individuals until later in the season. We will also examine the effectiveness of vaccination policies over a multi-year time, such as different vaccinations for individuals who have had previous influenza, and consideration of every-other year vaccines, Finally we will examine community-level interventions, such as school closures and working from home to impact the spread of influenza over a season. As a CDC Influenza Modeling Center, we will also collaborate with other centers to develop rapid responses to current influenza threats, to share data, models and results to provide higher confidence to the CDC that model-based recommendations can be used to formulate local, state and national influenza policy.",,2025,University Of Pittsburgh At Pittsburgh,750000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control | Policies for public health, disease control & community resilience",Immunity | Disease models | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P22885,5U01IP001137-04,"RFA-IP-20-003, FluMod - Center for the Multiscale Modeling of Pandemic and seasonal Flu Prevention and Control","PROJECT SUMMARY In this proposal we plan to contribute addressing the above foundational and operational challenges by advancing the science of influenza modeling and contributing novel methods and data sources that will increase the accuracy and availability of seasonal and pandemic influenza models. To address these challenges, we plan to build on the unique mechanistic spatially structured modeling approaches developed by our consortium, that includes stochastic metapopulation models and fully developed agent-based models nested together in our global epidemic and mobility modeling (GLEAM) approach. The objective of this project is to generate novel and actionable scientific insights from dynamic transmission models of influenza transmission that effectively integrate key socio-demographic indicators of the focus population, as well as a wide spectrum of pharmaceutical and non-pharmaceutical interventions. Our proposed work in specific aim 1 (A1) will leverage our global modeling (from the global to local scale) framework that can be used to explore the multi-year impact of influenza vaccination, antiviral prophylaxis/treatment, and community mitigation during influenza seasons and pandemics. Our specific aim 2 (A2) will focus on using high quality data to model heterogeneous transmission drivers and novel contact pattern stratifications that will allow us to guide mitigation strategies and prioritization for interventions. In our Aim 3 (A3) we will use artificial intelligence approaches to identify interventions that are particularly synergistic and well-suited to particular epidemic scenarios, for seasonal and pandemic influenza. Our overarching goal is to provide a modeling portfolio with flexible and innovative mathematical and computational approaches. We aim to address several questions commonly asked about seasonal and pandemic influenza and match these with analytical methods and outbreak projections. The modeling and data developed in this project can help facilitate and justify transparent public health decisions, while contributing to the definition of standard methods for model selection and validation. Finally, our influenza modeling platform can also benefit the broader network of modeling teams and can be used to improve result sharing and harmonization of modeling approaches.",,2025,Northeastern University,750000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Approaches to public health interventions,2020 +P22886,5R01AI150885-03,High-throughput assays and small-molecule discovery of antiviral candidates targeting influenza hemagglutinin,"PROJECT SUMMARY / ABSTRACT Influenza A viruses exhibit extreme diversity as exemplified by the multiple serotypes of the hemagglutinin (HA, H1-H18) and neuraminidase (NA, N1-N11) surface antigens. To date, only 3 of 198 possible combinations of HA and NA in avian and other animal reservoirs have been associated with human pandemics (H1N1, H2N2, H3N2). Recent appearances of H5N1, H6N1, H7N7, H7N9, H9N2, and H10N8 in humans are constant reminders of the potential for devastating new pandemics. Influenza B viruses with its two lineages further increase the health and economic burdens of seasonal influenza. No effective antiviral drugs are currently available for preventing entry of influenza A or B viruses into host cells (scientific premise). However, relatively recent discoveries of broadly neutralizing antibodies to human influenza viruses and concomitant structural studies have identified sites-of-vulnerability on the HA in pandemic, seasonal, and emerging influenza viruses. These HA surface sites include the receptor binding site and membrane-proximal stem housing the fusion machinery, both of which are essential for cellular infection. Common features for recognition of these sites can now be exploited in design of small molecules to ultimately develop broadly applicable influenza antivirals. Here, we will employ this structural information into the optimization and execution of high-throughput assays to identify new small-molecule scaffolds that target the highly conserved and vulnerable stem-binding site. High- throughput screening will be performed in parallel on representative HAs from influenza A group 1 against 600K structurally diverse molecules (SA1). We will also subject group 2 and influenza B HAs to a 300K compound screen (SA2). Validated hit compounds will be prioritized based on affinity and breadth across HAs and top candidates will be rigorously optimized into lead molecules by x-ray structure-based design cycled with medicinal chemistry. Biophysical binding, cellular infectivity and resistance assays (e.g., combinatorial viral libraries of HA mutants) will aid in iterative design, selection, and characterization of potential novel therapeutic candidates with favorable drug-like properties. All of these methods are actively employed in the Wolan and Wilson laboratories. As proof-of-concept for this approach, we identified a molecule with modest affinity to the stem of group 1 HAs with an HT assay of our own design. Its co-crystal structure with HA provided critical information towards design and synthesis of a focused compound library, which we used to produce a stereoselective molecule with nanomolar affinity and antiviral activity. Our overall goal is to identify and improve molecules with broad potency against the stem of groups 1 and 2 as well as flu B HAs. To our knowledge, we are the first to design an assay against group 2 and flu B HAs amenable to HTS (innovation). We anticipate that several classes of stem-targeted compound scaffolds will be identified with nanomolar affinity to HAs with cellular antiviral activity and suitable PK-ADME properties. Future efforts will include animal models of influenza infections to further validate our antivirals with the ultimate goal of combatting future influenza pandemics and seasonal epidemics.",,2025,"SCRIPPS RESEARCH INSTITUTE, THE",678526,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22887,1F31HL164049-01A1,Duration and Function of Lung Tissue Resident CD8+ Memory T cells,"PROJECT SUMMARY/ABSTRACT Influenza is a respiratory virus that infects an estimated one billion people around the world annually. While there is an influenza vaccine, it is typically only 40-60% effective and people must receive it every year. Additionally, the vaccine does not protect against future, and possibly pandemic, strains of influenza and thus there is a major need for new vaccination strategies. CD8+ T cells can provide cross protection against different strains of influenza because they recognize internal epitopes that are conserved. Specifically, due to their position in the lung, CD8+ tissue resident memory T cells (TRM) can rapidly respond to infection and mediate protection by reducing viral loads and immunopathology. In mice, studies have shown that influenza-specific CD8+ lung TRM have limited durability, but it is unknown how long lung TRM survive in humans. Additionally, the mechanisms by which lung TRM cytokines reduce viral loads and immunopathology is unknown in mice, and even less is known about the function of lung TRM in humans. Here, we propose a series of experiments to fill these critical gaps in knowledge. In Aim 1, we will use longitudinal bronchoalveolar lavage samples from lung transplant patients and antibodies specific for mismatched HLA alleles between recipient and donor to track the duration of donor lung TRM and the development of recipient lung TRM by flow cytometry. Additionally, we will determine the dynamics of flu-specific human lung TRM by performing immunophenotyping on longitudinal bronchoalveolar lavage, blood, and nasal lavage samples from lung transplant patients that become infected with influenza. In Aim 2, we will obtain healthy lungs that are unable to be transplanted in order to examine the effector functions of human lung TRM. Lung cells will be stimulated with influenza peptide pools to determine the cytokines produced by influenza- specific lung TRM, and the impact those cytokines have on neighboring cells in the lung tissue. Additionally, we will then use mice to mechanistically determine the effect of individual lung TRM cytokines to reduce viral loads and activate neighboring innate cells. Through this proposed work we hope to better understand the role that human lung TRM play in the immune response to influenza. Lastly, as lung TRM are generated in response to respiratory viruses, and not just influenza, results of this study could provide insights into the immune system that could improve vaccine design for all respiratory viruses and aid in the prevention of future global pandemics.",,2025,EMORY UNIVERSITY,47694,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P22888,5R01AI147109-04,Rapid Manufacturing of a Universal Flu Vaccine Using TMV-conjugated Centralized Antigens,"Project Abstract This interdisciplinary proposal brings together three highly successful but independent technologies to create an effective and broadly neutralizing universal influenza vaccine. Our approach combines breath of immunity, by using a consensus HA strategy, production speed and capacity by working with Kentucky BioProcessing (KBP), who can express HA protein in plants, and vastly improved subunit vaccine potency using a TMV-HA conjugation approach to create a candidate universal influenza virus vaccine. Based on our preclinical data on three influenza A strains, we expect our approach will drive long term immunity that is balanced between antibody and cellular immunity, providing potential for overlapping mechanisms of immune protection. We bring together a strong team of different disciplines with a combined goal to quickly show proof of concept with H1, H3, H5, and M2e antigens. Our Specific Aims are as follows: 1) Production of TMV-HA conjugates of centralized H1, H3, H5 genes and M2e peptide, 2) Immune response analysis, murine challenge studies and 3) Translational and ferret studies of TMV-HAc and TMV-M2e vaccines. Dr. Weaver has developed a computational method to express an ancestral sequence of HA, representing a consensus of sequences within an Influenza subtype. These vaccines protect against drifted seasonal influenza variants better than a traditional trivalent inactivated virus vaccine. In partnership with KBP, we will use established plant expression methods to produce centralized HA proteins, with the capacity to produce protein for the planned studies and for future clinical trial development. HA consensus protein will be fused to the surface of Tobacco Mosaic virus (TMV) by chemical conjugation, a method developed by Dr. McCormick to improve HA subunit vaccine potency. TMV-HA vaccines will also be combined with a highly conserved M2e peptide vaccine, to broaden protection and reduce vaccine dose. Immunological analysis will be used to confirm vaccine potency, in order to optimize dose, schedule and route of administration. Vaccine efficacy and broadly protective immunity will be confirmed by lethal influenza challenge using 9 divergent virus types in a murine model of disease. Finally, vaccine formulations will be re-tested in ferrets, a models of influenza infection which more closely mimics the progress of disease in humans. Our vaccine is designed to drive local and systemic immunity after either intranasal or intramuscular routes of administration, and we will use immunogenicity and pathogen challenge data to define an optimized single dose vaccine formulation. Our goal is to generate an effective universal vaccine against influenza that can be manufactured at scale, with significant potential for translation into a universal vaccine product that is ready for clinical testing.",,2025,UNIVERSITY OF NEBRASKA LINCOLN,661752,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22889,1R44AI179440-01,Clinic-Ready MACH-1 Gene Gun for delivery of a universal influenza DNA vaccine,"PROJECT SUMMARY Orlance has developed a lead universal influenza (UFlu) DNA vaccine to address the need for a vaccine that can protect from annual influenza and the emergence of new variants that could cause future pandemics. Our UFlu vaccine is a multi-dose vaccine designed to induce systemic and mucosal immune responses that can prevent transmission and minimize disease from currently circulating and emerging strains by inducing broad antibody and cellular immune responses that target conserved viral sequences common across all influenza subtypes. Under previous SBIR funding, we showed that our gene gun (GG)-delivered UFlu DNA vaccine induced broadly specific (universal) antibody and T cell responses and protection from diverse influenza challenges in rodents and nonhuman primates. This vaccine is nearing Phase 1 human trials and will require a clinic ready GG device to administer it. Here, we propose to continue developing our promising MACH-1TM GG to deliver the lead UFlu DNA vaccine and other lead vaccines to humans. The MACH-1 is a needle-free device that delivers DNA- and/or RNA-coated gold microparticles directly into epidermal cells using high pressure gas. It is pain free, requires substantially lower doses of DNA or RNA to induce protective immunity compared to other delivery methods, and has been engineered with several innovations to maximize efficiency and reproducibility of delivery. Here, we will: improve the MACH-1 by making it portable and easier to use (Aim 1); develop a GMP- scalable DNA vaccine formulation into fill and finish disposable dosing units (Aim 2), and evaluate safety, immunogenicity, and efficacy of the UFlu vaccine delivered by the improved MACH-1 in mice and swine models (Aim 3). Successful completion of these Aims will result in Investigational New Drug (IND)-enabling documentation for the delivery system device and formulation platform necessary to advance our MACH-1 delivered UFlu DNA vaccine to Phase 1 trials.",,2026,"ORLANCE, INC.",996500,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration | Vaccine trial design and infrastructure,2023 +P22890,1R56AI168087-01A1,Harnessing ZBP1-triggered cell death to enhance influenza vaccine responsiveness,"PROJECT SUMMARY/ABSTRACT Vaccination represents the most effective means of preventing influenza A virus (IAV) infections. Current approaches to IAV vaccines primarily target the HA protein, but HA undergoes significant antigenic drift and is thus a poor target for lasting humoral immunity. An alternative approach to developing a universal IAV vaccine is to target internal viral proteins (such as the nucleoprotein), which are also highly conserved between most IAV strains. A major roadblock to this approach, however, is a lack of adjuvants that trigger the right kind of immune response - a ‘type I’ (or Th1/CD8+ T-cell driven) response - to these internal antigens. In this proposal, we outline a new strategy that seeks to harness immunogenic cell death as a means of activating type I immunity to IAV vaccines. We have identified a host signaling pathway which accounts for almost all IAV-activated immunogenic death in infected cells, including primary airway epithelial cells, macrophages and DCs. This cell death pathway is initiated when the host sensor protein ZBP1 detects IAV genomic RNA and activates parallel pathways of programmed necrosis (necroptosis) and apoptosis to kill the infected cell and instigate CD8+ T cell-mediated adaptive immune responses. Adding to the attractiveness of ZBP1-initiated cell death as a vaccine approach are our discoveries, first, that IAV produces a new form of double-stranded RNA - termed Z-RNA - to activate ZBP1. Z-RNA is thus a new PAMP, and can be readily harnessed to trigger immunogenic cell death and adjuvant IAV vaccines. Second, ZBP1 initiates necroptosis from the nucleus, resulting in nuclear envelope rupture and release of highly-immunogenic nuclear DAMPs and IAV antigens. Nuclear necroptosis is even more immunogenic than conventional (cytoplasm-initiated) necroptosis. As ZBP1-driven immunogenic cell death (both apoptosis and nuclear necroptosis) is important for effective anti-IAV cytotoxic T cell responses, our discoveries allow us to propose that Z-RNAs are potent new adjuvants for activating type I immune responses to IAV, and that recombinant IAVs engineered to produce Z-RNAs represent new type I immunity-activating vaccines. In this proposal, three labs with strong expertise in IAV cell death signaling (Balachandran), recombinant IAV technology (Langlois), and pathogenesis/vaccine strategies (López) will unite to identify IAV-generated Z-RNAs that activate ZBP1 (Aim 1); determine which stromal and immune cell types die by ZBP1-mediated mechanisms to initiate and regulate effective adaptive immune responses (Aim 2); and test if triggering ZBP1-mediated cell death with synthetic and virus-generated Z-RNAs can be leveraged to inform and supply next-generation vaccines capable of providing effective cross-protective immunity to IAV (Aim 3).",,2024,RESEARCH INST OF FOX CHASE CAN CTR,833534,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P22892,1R44AI174337-01,Development of a shelf-stable universal mucosal HA-vaccine for the prevention of influenza,"PROJECT SUMMARY TFF Pharmaceuticals (TFFP) is developing a shelf-stable thin-film freeze (TFF) dry powder universal flu vaccine. Commercialization of this product would provide the first vaccine that is at least 75% effective against symptomatic influenza virus infection, with the added benefit of easy delivery and storage at room temperature to facilitate broad, cost-effective distribution. With NIAID’s Collaborative Influenza Vaccine Innovation Center funding, the University of Georgia (UGA) has developed a recombinant vaccine against all influenza virus hemagglutinin (HA) proteins and demonstrated its efficacy in mice and ferret models. If shown to be effective in humans, it could provide broad protection against both known and previously unrecognized strains of influenza virus, establishing a new standard of protection against seasonal viruses while heading off the emergence of novel strains in the future. A traditional liquid version of this vaccine would provide enormous benefits relative to the current seasonal vaccines, but they require cold-chain handling that increases costs and presents substantial barriers to establishing a stockpile or distributing the vaccine in underdeveloped areas. To address these challenges, UGA is collaborating with TFFP to develop a dry powder formulation of the universal vaccine. Using a thin-film freezing (TFF) technique, TFFP can formulate and manufacture dry powder vaccines that maintain immunogenicity while withstanding unintentional freezing. The vaccine powder can be stored and shipped free of cold-chain handling with extended stability for stockpiling. Our preliminary studies demonstrate that a reconstituted TFF-formulated version of UGA’s HA vaccine elicited the same level of immunogenicity and achieved the same protective efficacy as the original liquid vaccine in BALB/c mice. A follow up study in ferrets confirmed the efficacy of the TFF-HA vaccine in reducing viral titers in nasal swabs and preventing weight loss. In this Direct to Phase II SBIR, TFFP and UGA propose to evaluate different adjuvants for intranasal and pulmonary inhalation delivery and confirm the stability, immunogenicity, and efficacy of the TFF-formulated HA vaccine in ferrets, the gold standard for influenza virus vaccine testing (Aim 1). Aim 2 will scale-up manufacturing of the inhaled TFF-HA dry powder vaccine for subsequent toxicology studies in rats (Aim 3); we will also develop GMP formulation and manufacturing for clinical trials. This project is expected to provide all required IND- enabling studies to prepare an IND package and ultimately advance to human testing. A dry powder vaccine would eliminate challenges in shipping and storage, reducing the cost and complexity of vaccine stockpiles and vaccination campaigns. A shelf-stable universal influenza virus vaccine would also revolutionize the public health approach to influenza, providing a low-cost, broadly disseminable vaccine that is at least 75% effective against sympotmatic influenza virus infections regardless of which viral strain emerges each year.",,2026,"TFF PHARMACEUTICALS, INC.",864948,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P22893,1R21AI173593-01,Harnessing Age-Associated B cells for a Universal Influenza Vaccine for the Aged,"ABSTRACT: Harnessing Age-Associated B Cells for a Universal Influenza Vaccine for the Aged. With age, the generation of T follicular helpers from naive CD4 T cells, and germinal center B cells from follicular B cells, that are both needed for the generation of high affinity antibody (Ab), become highly compromised. Most current vaccines for influenza in the elderly are not effective at inducing these critical responses. Thus, the elderly, though protected by Ab already in place for pathogens encountered earlier in life, are highly susceptible to new strains of virus (e.g. influenza) and newly emerged pathogens (e.g. pandemic influenzas, COVID-19). We described the generation of an unusual population of Ab-secreting B cells that developed to live influenza infection in aged mice. We found they were derived from stimulation of recently described ""age-associated B cells"" (ABC) of a naïve sIgD+ phenotype. In the aged, these influenza-induced ABC (iABC) are generated independently of CD4 T cell help, but strictly depend on stimulation by pathogen-associated ""danger"" signals and thus they are generated well in aged infected mice. Notably, ABC are the predominant naïve B cells that respond in aged mice. Here we will determine the potential of IgD ABC to respond to influenza infection and generate Ab-secreting cells (AbSC) effector iABC that are either recirculating or are tissue resident. We will determine if they give rise to B cell memory, both resting memory and long-lived Ab-secreting cells, and if these are found in the lower respiratory tract (lung) and upper respiratory tract (URT):nasal tissues and nasal associated lymphoid tissue- NALT), as well as the spleen and BM. We will determine the contribution of ABC-derived effector and memory subsets and the Ab they produce in these the different sites to protection from reinfection. We will ask how long- lived are the memory cells in distinct sites. We will compare the ability of live influenza virus, whole inactivated virus, and mRNA-LNP HA vaccine to generate the recirculating and tissue resident effector and memory subsets and to induce protective immunity. These results will give us new insights into this novel age-associated immune pathway and give us important new insights into whether harnessing the aged ABC response can provide superior protection in the aged. It will provide indications of what general vaccine strategies are likely to be needed to immunize the ABC in the elderly. These findings could lead to a more Universal vaccines that can provide robust protection to the elderly, who are currently highly vulnerable.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,251250,Other,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22894,5R01AI146588-03,Biomimetic nanoparticles to enhance the breadth of influenza vaccines,"Abstract Current influenza (flu) vaccines are effective only for closely matched flu viral strains and must be updated annually to address constant antigenic shift/drifts of surface hemagglutinin (HA) and/or neuraminidase (NA) of the virus. Even with annual update, there have been years in which flu vaccines were ineffective due to significant differences in antigenicity of HA and/or NA between the strains used for preparing the vaccines and the circulating ones, leaving us at high risk of pandemics in case a new and highly pathological virus emerges. It is without any doubt that a Universal flu vaccine that can protect against both seasonal (matched or mismatched) and pandemic flu viruses is urgently needed, but it remains an alchemist's dream  so far. We developed a novel adjuvant by encapsulation of cGAMP, an agonist of the stimulator of interferon (IFN) gene (STING), into pulmonary surfactant (PS)-biomimetic liposomes (PS-GMNP). The adjuvant, alongside an inactivated flu vaccine, robustly stimulated humoral and CD8+ T cell immune responses that resemble those ocurring during the early phase of viral infection both in magnitude and in dynamics. Strikingly, a single dose of PS-GMNP-adjuvant flu vaccine elicited strong cross-protection against a lethal challenge of diverse heterosubtypic flu A viruses as early as 2 days after immunization. While stimulating robust heterosubtypic immunity, the adjuvant did not cause any adverse events in lung histology, body weight or temperature, in sharp contrast to the severe lung inflammation and death caused by flu viral infection. In this proposal, we will investigate the cellular and humoral immune responses essential to the cross-protection induced by PS- GMNP-adjuvanted flu vaccines. Specifically, we will determine whether PS-GMNP can expand cross-reactive CD8+ T cells and induce broadly neutralizing antibodies (bnAbs), pivotal to PS-GMNP-induced cross- protection. In Aim 2, we will preclude any adverse effects of pre-existing immunity on the adjuvanticity of PS- GMNP and extend the cross-protection to pre-pandemic wild type H5N1 and H7N9 viruses to establish its clinical potentials. Distinguished from conventional adjuvants that activate primarily antigen-presenting cells (APCs), cGAMP delivered by PS-GMNP activated both alveolar macrophages (aMɸ) and alveolar epithelial cells (AEC), which can be crucial since similar activation of these two types of cells is also observed during flu viral infection. Two alternative approaches will be employed in Aim 3 to corroborate indispensable function of AEC and/or aMɸ in PS-GMNP-mediated heterosubtypic immunity, including a blockade of cell-gap junctions and generation of chimeric mice of wild type and STING-deficient bone marrow (BM) cells. The study, if successful, could provide invaluable information about clinical potentials for PS-GMNP to widen the breadth of existing flu vaccines toward a “Universe” one, which will have a huge and immediate impact on global health.",,2025,MASSACHUSETTS GENERAL HOSPITAL,562273,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | H7,,,,H5N1,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +P22895,5U01IP001189-02,"RFA-IP-22-004, Component A _ Credible Effectiveness Measures of Seasonal Influenza, COVID-19 and Other Respiratory Virus Vaccines against Ambulatory Care for Acute Illness in Texas (and Component D).","COMPONENT A - PROJECT SUMMARY/ABSTRACT: Influenza (Flu) viruses are constantly evolving, requiring vaccines to be reformulated every season. New SARS- CoV-2 (SC2) variants have caused recurrent Coronavirus Infectious Disease â€Â"" 2019 (COVID) surges in different regions of the United States through the winter of 2021-22. Estimating ongoing real-world Flu and COVID vaccine effectiveness (VE) against ambulatory care for acute illness (ACAI) are essential in evaluating the protection provided by nationwide vaccination programs and for monitoring the duration of protection afforded by respective vaccines each of which are high priorities for fulfilling the CDC’s mission of serving as the nation’s health protection agency. Our long-term research goal is to advance the understanding of the epidemiology and prevention of respiratory virus (RV) infections (i.e., seasonal and pandemic influenza, SC2 and Other Respiratory Viruses (ORVs) such as Respiratory Syncytial Virus [RSV]) while reducing the burden of disease and improving the health of the population. We plan to systematically evaluate the VE against ACAI associated with lab-confirmed influenza, COVID and vaccine-preventable ORVs with respective CDC recommended vaccinations in the Baylor Scott & White Health, Central Texas (BSWCTX) enrollment eligible population. The objective is to obtain reliable vaccination information and to provide accurate interim and annual estimates of VE to prevent ACAI in respective RV vaccine age-eligible population. Our central hypothesis is that timely and accurate measurement of VE and burden of illness due to vaccine preventable RVs is sustainable. The rationale is that by assessing the interim and annual VE against vaccine preventable RVs, the CDC ACIP can modify recommendations for receiving the vaccines and booster doses as well as use of appropriate antiviral agents. The specific aims are to: 1) Measure effectiveness of seasonal and pandemic Flu, COVID and vaccine-preventable ORV vaccines against ACAI for respective lab-confirmed mild to moderate infection in at least 1,000 children and adults from the 2022-23 to 2026-27 seasons. 2) Monitor ongoing Flu and SC2 viral evolution by genomic sequencing among at least 1,000 enrolled children and adults from the 2022-23 to 2026-27 seasons. 3) Perform potentially year-round SC2 surveillance during periods when Flu viruses are not circulating to measure current COVID VE against ACAI for lab-confirmed mild to moderate SC2 infection in children and adults from the 2022-23 to 2026-27 seasons. To accomplish these aims, we will estimate real-time VE in the ambulatory setting using a test-negative design, estimate burden of illness of vaccine preventable RVs in the BSWCTX burden subset, and examine factors affecting VE. The proposed research is innovative as we have adapted methods to include verified vaccinations and accurate lab diagnosis of RV infections with one or both influenza and SC2 in participants who are systematically screened for eligibility and enrolled using a well-defined ACAI case-definition in our approach, enabling us to aptly measure VE and burden of illness of influenza, COVID, and ORVs in the West South Central United States.",,2027,BAYLOR RESEARCH INSTITUTE,1400000,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Impact/ effectiveness of control measures | Disease surveillance & mapping | Characterisation of vaccine-induced immunity",2022 +P22896,2R42AI162590-02,Treatment of Inflammatory Complications of Respiratory Infection,"Abstract Respana Therapeutics is advancing a proprietary first-in-class therapeutic monoclonal antibody (mAb), RT- 002, for the treatment of debilitating and often lethal inflammatory complications associated with acute respiratory conditions. We have identified a lead candidate, RT-002, and an equally promising alternative. RT-002 targets the surfactant protein A receptor SP-R210, a host-mediated target that holds the promise of efficacy regardless of pathogen evolution. Rigorous in vivo mouse studies have demonstrated not only reduction in mortality but restoration of lung health as well. Furthermore, RT-002 does not target an individual cytokine pathway, which can have negative effects. RT-002 thus has the potential to fill a significant gap in the therapeutics arsenal for influenza since the most widely used tools are vaccines to prevent infection and antiviral drugs to stop infection; however, these are limited by partial efficacy, vaccine hesitancy, and emergence of drug resistance. The objective of this Phase II proposal is to continue development of RT-002 and the backup with the goal of advancing the therapeutic toward clinical trials as quickly and efficiently as possible. Specifically, the Aims include: 1) Determine RT-002 pharmacological action in human blood through our functional immunophenotype assays to discern RT-002 target engagement and immune activation in human blood that will inform therapeutic design in alleviating aberrant immune activation in critically ill patients; 2) Establish pharmacological activity of RT-002 treatment for severe influenza utilizing humanized FcRn mice to establish safety, toxicity, pharmacodynamics, dosage, schedule, and duration of treatment to de-risk the development of RT-002 towards clinical trials in humans; and 3) Establish foundations for Phase I/IIa clinical trials for transition of RT-002 to clinical testing through existing partnerships with contractual research organizations, critical illness, and critical trials experts for production and GMP certification of RT-002 in stable CHO cells, and organization and planning of critical parameters from Aims 1 and 2 that are needed for pre-IND consultation with the FDA and the design of phase I/IIa clinical trials. Successful completion of the Aims will allow rapid progress toward IND-enabling studies, IND filling and initial clinical trials of a new therapeutic for an important and largely unmet clinical need for the treatment of life- threatening influenza illness.",,2026,"RESPANA THERAPEUTICS, INC.",1000000,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical | Non-Clinical,Protocol,Coronavirus,Unspecified,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies | Therapeutics logistics and supply chains and distribution strategies",2022 +P22897,1R21AI175965-01,Molecular epidemiology of respiratory virus exposure in elementary schools,"PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding the extent to which the school environment contributes to respiratory virus exposure, and less is known about potential environmental interventions to reduce exposure. Our long-term goal is to create healthy indoor school environments for children. The overall objective of this application is to identify modifiable factors of respiratory virus exposure in elementary schools in order to reduce asthma morbidity. We will combine novel approaches to quantify and characterize the respiratory virome in schools by leveraging the robust infrastructure of the School Inner-City Asthma Intervention Study (SICAS-2, ClinicalTrials.gov NCT02291302), a randomized controlled trial conducted by our group of a placebo-controlled classroom high efficiency particulate air (HEPA) cleaner intervention. We will test our central hypothesis that schools are a source of high respiratory virus exposure that affects asthma morbidity through the following specific aims: (1) To compare respiratory virus exposure in schools as compared to homes by using a hybrid capture panel to recover genomes of detected respiratory viruses; (2) To identify factors predicting respiratory virus exposure in schools including the efficacy of portable HEPA cleaners in reducing classroom respiratory virus exposure; (3) To determine the association between the classroom respiratory virome and asthma symptoms in elementary school children. The approach is innovative, because we are simultaneously interrogating all major human respiratory viruses in the school environment. The proposed research is significant, because it will identify the magnitude of exposure to respiratory viruses in schools and potential environmental factors that can serve as future targets of intervention. If the HEPA intervention can reduce respiratory virus exposure, it is an immediately actionable and practical intervention to create safer indoor environments for elementary school children. Results from this proposal may be generalizable to other public indoor settings.",,2025,MASSACHUSETTS GENERAL HOSPITAL,267878,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience",Environmental stability of pathogen | Disease transmission dynamics | Approaches to public health interventions,2023 +P22898,5R42AI155039-03,Development of 4-(aroylamino)piperidine-based entry inhibitors as anti-influenza therapeutics,"Influenza A viruses belong to the orthomyxoviridae family, and have a negative-sense, segmented RNA genome, which can cause seasonal or pandemic flu with high morbidity and significant mortality. Vaccination is the most prevalent prophylactic means for controlling influenza infections. However, an effective vaccine usually takes at least six months to develop. Furthermore, vaccination has limited effectiveness in the treatment of immunocompromised patients, and its effectiveness is also limited during a pandemic. The current therapeutic options for flu infections are all based on the neuraminidase inhibitors (NAIs; oseltamivir, zanamivir and peramivir), while the influenza M2 ion channel blockers (amantadine and rimantadine) are not now recommended since all of the circulating influenza strains have acquired resistance. (Xofluza, a polymerase acidic endonuclease inhibitor, has just been approved in 2018 and is yet untried during a flu season.) The rapid emergence of the NAI-resistant strains of influenza A viruses strongly suggests that NAIs alone may not be sufficient as effective therapies, and thus new treatment options targeting the other viral/host factors are urgently needed. This application defines a plan to develop potent, small molecule inhibitors, which block entry of influenza A viruses. We have identified compounds that inhibit entry of infectious influenza A viruses, with IC50 values in the nanomolar range. We have synthesized structurally diverse analogs of the anti-influenza hit series using structure-activity relationships (SARs) to improve potency and selectivity; validated the lead inhibitor candidates in the infectious assay and investigated the mechanism of action (MOA) of the these inhibitors; and selected anti-influenza inhibitors with excellent in vitro potency and selectivity values and druglike in vivo pharmacokinetic properties. In this Fast Track STTR Phase I &II application, we propose four specific aims: (1) optimize the lead scaffold and select development candidates; (2) investigate the mechanism of action (MOA) of the advanced lead compounds with HA proteins; (3) evaluate the pharmacokinetics/toxicokinetics of the advanced lead compounds; and (4) preclinical development.",,2025,"CHICAGO BIOSOLUTIONS, INC.",999369,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22900,5R01AI144798-03,Pandemrix and T Cell Immunology in Narcolepsy,"ABSTRACT: Genetic studies indicate a strong (97%) association of narcolepsy with HLA-DQA1*01:02/DQB1*06:02 (DQ0602), weaker associations with HLA-DP and class I HLA- A*11:01, and effects in other immune related genes such as the TCR αβ loci. The disease is caused by the loss of hypocretin (HCRT)/orexin neurons, as loss of HCRT or HCRT receptors recapitulates symptoms in animal models. Results from our laboratory and from others indicate that a critical step in the disease process is a CD4+ T cell autoimmune response targeting HCRT itself, notably a DQ0602 restricted response to the amidated, C-terminal end of secreted HCRT peptides (HCRTNH2). Indeed, increased T cell response to HCRTNH2 presented by DQ0602 is observed in narcolepsy (our observation), followed by a broader CD4+ T cell responses to other HCRT fragments presented by other HLA class II molecules (other investigators), a result of epitope spreading. This is likely followed by a CD8+ T cell response to HLA class I presented antigens that results in hypocretin cell death and life-long narcolepsy. Unique to narcolepsy, a known environmental factor, the flu, has been associated with initiation of the autoimmune process. Indeed, an increased incidence of narcolepsy in children has been observed following the 2009-2010 pH1N1 Influenza pandemic in China and following vaccination with Pandemrix (GSK), an AS03 adjuvanted pandemic H1N1 2009 (pH1N1) vaccine, but not other vaccines. These observations indicate that epitopes within the pH1N1 virus and vaccine can precipitate narcolepsy in some individuals, findings substantiated by the fact narcolepsy patients have increased T cells binding NP17-31 and pHA273-287, a flu hemagglutinin fragment with significant HCRTNH2 sequence homology. This mechanism is also supported by our preliminary data suggesting TRAJ24 and TRBVB4-2 involvement in pHA273-287, NP17-31 and HCRTNH2 TCR responses, as these TCR segments are modulated by SNPs associated with narcolepsy. In this application, we will further characterize antigenic differences in Pandemrix, Arepanrix and Focetria, vaccines used in the 2009-2010 pH1N1 vaccination campaign, capitalizing on the observation that they have differential risk for precipitating narcolepsy. Our hypothesis, supported by preliminary data, is that Pandemrix contains more pHA273-287 peptide, the main mimic of HCRTNH2 autoimmune responses. In addition, we will continue isolation and characterization of Pandemrix/H1N1 reactive and HCRTNH2 DQ0602 restricted CD4+ T cells. Our hypothesis is that we will ultimately discover pHA273-287/HCRTNH2 and other flu/HCRT cross-reactive cells that use TRAJ24 and TRBVB4-2 segments. Finally, we aim to characterize the phenotype of the corresponding pathogenic cells through single cell sequencing. This high impact study is expected to eventually lead to a) demonstration of molecular mimicry in narcolepsy and b) improved safety of influenza vaccines.",,2025,Stanford University,717697,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P22901,5U01EB029085-06,A Microphysiological Mimicry of Human Lung-Bone Marrow Organ-Organ Crosstalk On-a-Chip,"PROJECT SUMMARY. Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 20 years. Influenza A viruses (IAVs) comprise 50% of the emerging respiratory viruses and can cause substantial morbidity and mortality. IAVs can infect a diversity of avian and mammalian species, including humans, and have the remarkable capacity to evolve and adapt to new hosts. Despite the tremendous progress made in virology and epidemiology, which subtype or strain of IAV will cause the next outbreak remains unpredictable. Importantly, there is no clinically simulating, pathophysiologically relevant, and readily available in vitro multi-organ system for predicting the pathogenicity of emerging and re-emerging influenza viruses in humans. Recent compelling evidence have revealed opposing roles for two major classes of bone marrow (BM)-produced innate immune cells in shaping the outcome of IAV infection, with neutrophils offering protection and increase in circulating monocytes being associated with increased pathology. Thus, selective mobilization of either of these two distinct cell types in response to pulmonary infection with IAV can indirectly reveal potential pathogenicity of a given viral strain. The overarching goal of this project is to develop a highly innovative, reductionist, yet advanced and complex, physiologically relevant in vitro model of influenza infection in humans utilizing Organ-on-Chip technology in order to predict virulence and infectivity of different IAV strains, by reproducing clinically and in vivo-observed immunological correlates of infection severity. More specifically, we will engineer a first-in-kind fluidically integrated multi- organ system that recreates BM-lung axis, using primary human-derived cells, for real-time analysis of inflammation and leukocyte mobilization in response to influenza challenge. Our central hypothesis is that this dynamic living microsystem can recapitulate differential immune cell mobilization and tissue pathology in response to high-pathogenicity vs. low-pathogenicity IAV infections in vitro. To address the hypothesis, we propose the following specific aims: (1) to engineer a living and hematopoietically active human BM-on-a-Chip and microfluidically link it to a human Lung Small Airway-on-a-Chip that our team has previously developed and characterize homeostatic physiology and organ-organ crosstalk; and (3) to challenge the BM-Lung microsystem with airborne IAVs under rhythmic breathing and reproduce differential leukocyte mobilization and tissue damage in response to distinctly pathogenic viral strains. Such a novel platform holds great potential in emulating and predicting pathogenicity of IAVs (e.g., during outbreaks, pandemics or when presence of a highly virulent strain is speculated), utilizing human cells isolated from desired donor/patient populations, and without needing to adapt the virus for host (as required for some animal studies). In addition, it can considerably accelerate drug development studies by enabling personalized drug efficacy testing and identification of new therapeutic targets.",,2024,University Of Pittsburgh At Pittsburgh,382878,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2021 +P22902,5R01HL146479-04,Immune mechanisms of influenzaÃÃ'¢ÃÂ'Ã'€ÃÂ'Ã'induced exacerbation of atherosclerosis,"Immune mechanisms of Influenza-induced exacerbation of atherosclerosis Influenza A infection is a significant cause of mortality and morbidity worldwide. It is estimated that 3-4 million cases of severe illness and 300,000 deaths due to influenza infection occur annually. During influenza pandemics, the focus is on lung disease, which is the most common cause of death. However, recent epidemiological studies reported significant mortality associated with cardiovascular diseases (CVD) during influenza infection. Atherosclerosis is a common cause of coronary artery disease (CAD), including MI, stroke, and heart failure. The innate and adaptive immune response to modified lipids and vascular endothelial cells causes a series of events that result in plaque formation in medium to large-sized arteries. If inflammatory stimuli continue, plaques become vulnerable to rupture and can cause MI. However, the mechanism involved in the influenza-induced increase in MI incidence is not clear. Our long-term research goal is to understand the impact of lung-vascular interactions in atherosclerosis. The objective of this application is to determine how influenza infection directly or indirectly impacts the outcome of atherosclerosis. In Aim 1, we will characterize myeloid and lymphoid cellular subsets from lung, aorta, and spleen at various time points (early, peak, recovery phase) after fluorescent-labeled (Color-flu) influenza infection to track influenza virus along with the cellular recruitment to the vessel. We will then examine whether antigen presentation is impacted by oxidized LDL (oxLDL) using bone marrow dendritic cells (BMDCs) and T cell re- stimulation in vitro. In Aim 2, we will determine the role of type III IFNs (IFNÃŽÂ>>) systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza-induced exacerbation of atherosclerosis. Further, we will determine the effect of IFNÃŽÂ>> on foam cell formation in macrophages. Finally, we will determine the effect of conditioned media from influenza or type I (IFNβ), type II (IFNγ), and type III (IFNÃŽÂ>>)-treated human bronchial epithelial cells (HBE) on human primary aortic endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. In Aim 3, we will determine the effect of IL-17 neutralization systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza induced-exacerbation of atherosclerosis. Further, we will determine the effect of lung epithelial IL-17RC signaling during influenza infection in atherosclerotic Apoe-/- mice. Finally, we will determine the effect of conditioned media from influenza- infected or IL-17-treated human bronchial epithelial cells (HBE) on vascular endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. At the completion of these studies, we expect to have made mechanistic insights into the cellular trafficking, viral trafficking, systemic and local effects of IFNs and IL-17, and pulmonary epithelial IL-17 signaling in influenza-induced exacerbation of atherosclerosis that may help to identify immune-based therapeutic targets.",,2025,University Of Pittsburgh At Pittsburgh,389555,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +P22904,1R01GM152736-01,Novel Hybrid Computational Models to Disentangle Complex Immune Responses,"Most quantitative models in biomedical research have been formulated by ordinary differential equations (ODEs). Despite the great contributions ODEs have made to biology and beyond, the high-dimensional, time-dependent factors of the immune system still pose a significant challenge to the predictive value of ODEs as it would require several hundred equations and thousands of parameters to be estimated. The recent rise of machine learning as a powerful computational tool to integrate large datasets presents a special opportunity to deal with the inherent complexity of biological systems. However, machine learning approaches do not consider the mechanistic knowledge of the underlying interactions. Preliminary studies that combine ODEs and machine learning highlight that these computational algorithms could be on the cusp of a major revolution. Remarkably enough, however, no parameter estimation theory exists to integrate simultaneously both approaches. We propose to create new hybrid models and test their predictions in a mouse viral coinfection system to address a central vexation for infection biology which is how and when to modulate immune responses to mitigate mortality during lethal respiratory viral infection. At the interface between mathematical and life sciences, we will develop and analyze a novel suite of computational models that will integrate the underlying biological mechanisms to manage ill-posed problems and explore massive design spaces, allowing for robust predictions from complex biological systems. To validate and test our novel and foundational mathematical approaches, we will generate the biological data from a mouse infection system with a mild viral pathogen (rhinovirus) two days before infection with a lethal viral pathogen (influenza) that results in reduced disease compared to single infection alone. We hypothesize that this system can train our mathematical models in a natural way how the innate immune system can be manipulated to reduce mortality to lethal infections and beyond. Key model predictions will be tested by targeted immune system manipulation during lethal infection, paving the way to understanding the role of complex immune interactions in respiratory viral disease pathology.",,2026,University Of Idaho,171789,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Other,Unspecified,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2023 +P22905,1R21AI178155-01,High efficiency particulate air cleaner intervention to reduce respiratory virus exposure in elementary schools,"PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding the extent to which the school environment contributes to respiratory virus exposure, and less is known about effective environmental interventions to reduce exposure. Our long-term goal is to create healthy indoor school environments for children. The overall objective of this application is to identify environmental predictors of and potential interventions influencing respiratory virus exposure in elementary schools. We will extend the robust infrastructure of the School Inner-City Asthma Intervention Study (SICAS-2, ClinicalTrials.gov NCT02291302), a five-year randomized controlled trial conducted by our group of a placebo-controlled classroom high efficiency particulate air (HEPA) cleaner intervention to continue cohort recruitment in the post-COVID-19 pandemic period. We will test our central hypothesis that modifiable built environment factors influence airborne respiratory virus exposure and infection in elementary schools through the following specific aims: (1) To determine the efficacy of a randomized placebo controlled HEPA cleaner intervention in reducing classroom airborne respiratory virus exposure; (2) To determine the efficacy of a randomized placebo controlled HEPA cleaner intervention in reducing symptomatic and asymptomatic respiratory viral infections in asthmatic children. The approach is innovative, because we are simultaneously interrogating all major human respiratory viruses in the context of a school-based randomized trial focused on an environmental intervention. The proposed research is significant, because if the HEPA intervention can reduce respiratory virus exposure and infections in schools, it is an immediately actionable and practical intervention to create safer indoor environments for elementary school children. Results from this proposal may be generalizable to other public indoor settings.",,2025,MASSACHUSETTS GENERAL HOSPITAL,274887,Human Populations | Environment,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience","Environmental stability of pathogen | Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions",2023 +P22906,5R43AI170395-02,"Development of a single-dose self-amplifying RNA vaccine for boosting pre-existing influenza virus immunity, driving B and T cell responses to conserved targets","Project Summary While a universal influenza vaccine, providing life-long protective immunity against all current and future drifted and shifted subtypes of influenza virus after 2 or 3 doses, would be a game-changing solution to reducing the global burden of influenza and its associated morbidity and mortality, other approaches to solving this problem are urgently needed. There is still much to learn about immune responses to respiratory pathogens, such as influenza virus, and vaccine approaches that drive life-long immunity to respiratory viruses have yet to be demonstrated in humans. Therefore, we propose to develop a broadly protective influenza booster vaccine that can be administered, either seasonally or during pandemics, to individuals with prior exposures to either natural infection or seasonal vaccination. Given the non-uniform influenza immune history in a given population of individuals, it is likely that booster vaccines will need to be customized either at the individual or regional level, based on local influenza virus epidemiology or vaccine uptake. Nucleic acid vaccine platforms provide the ideal framework for such personalized-medicine approaches, due to the flexibility of development, as typified by the ongoing COVID-19 pandemic. As proof-of-concept, here we propose to apply our clinical-stage replicating RNA vaccine platform to develop a booster vaccine targeting the conserved hemagglutinin stem and nucleoprotein of group 1 influenza viruses and evaluating immunogenicity and efficacy against heterologous group 1 influenza virus infections in mouse and ferret models of pre-existing influenza virus immunity. These data will inform the feasibility of such an approach and characterize what types of pre-existing immunity, in terms of anti-hemagglutinin antibody specificity and magnitude, are required for booster vaccine efficacy. As these pre-existing antibody criteria are easily assessed in humans, it is likely that a personalized approach to influenza booster vaccination is achievable.",,2024,HDT BIO CORPORATION,192720,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity,2022 +P22907,5R01HL164821-02,Alveolar responses to viral lung infection,"PROJECT SUMMARY / ABSTRACT Significance. One-third of patients with severe lung infection by influenza A virus (IAV) develop secondary infection by inhaled Staphylococcus aureus (SA). Coinfection by IAV and SA causes about 30% mortality despite therapy. It remains unclear how IAV promotes secondary SA infection, particularly in lung alveoli. This issue is important because alveoli are the anatomical site of fatal SA-induced Acute Lung Injury (ALI), but alveolar defense mechanisms, including alveolar wall liquid (AWL) secretion, should prevent SA stabilization and coinfection initiation. The long-term objective of this proposal is to determine alveolar responses to IAV that promote secondary SA infection in alveoli, resulting in SA-induced alveolar damage, ALI, and mortality. The hypothesis is IAV lung infection inhibits AWL secretion, a homeostatic mechanism by which alveoli clear inhaled particles. The inhibition causes alveolar retention of SA and the secreted SA toxin, alpha hemolysin (Hla). The retention enhances alveolar contact with SA and Hla, promoting SA stabilization against the alveolar wall and Hla-induced alveolar fluid barrier loss, leading to alveolar edema and fatal ALI. In addition to directly supporting the hypothesis, preliminary data indicate IAV lung infection caused: (A) dephosphorylation, hence inactivation of the alveolar cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, the critical protein for AWL secretion; and (B) methylation of the CFTR-dephosphorylating protein, protein phosphatase 2A (PP2A) catalytic subunit (PP2Ac), which may promote PP2Ac-CFTR interactions. Specific Aims are as follows. Aim 1 will define the role of CFTR in alveolar retention of inhaled SA. Aim 2 will define the role of PP2Ac methylation in IAV-induced inhibition of AWL secretion. Since our preliminary data suggest CFTR and the PP2Ac- methylating enzyme, leucine carboxyl methyltransferase 1 (LCMT1) may represent new therapeutic targets to restore AWL secretion in IAV-infected lungs, Aim 3 will test the therapeutic potential of CFTR- and LCMT1- targeted approaches to protect against coinfection-induced alveolar damage, ALI, and mortality. These Aims will be achieved using our established methods, which include cell culture, mouse models of ALI, and real-time confocal microscopy of live, intact mouse and human lungs. Determinations in IAV-infected mice will include measures of: (1) alveolar retention of SA; (2) AWL secretion; (3) alveolar CFTR phosphorylation status; (4) alveolar PP2Ac methylation status; (5) SA- and Hla- alveolar epithelial damage and alveolar barrier loss; and (6) SA-induced pulmonary edema and mortality. We will use: (i) wild type mice treated with inhibitors of alveolar PP2Ac-CFTR and PP2Ac-LCMT1 interactions, including drug inhibitors, plasmid DNA encoding mutant proteins, and siRNA; and (ii) transgenic mice lacking alveolar epithelial CFTR and LCMT1 expression. This proposal is expected to achieve new insights into the molecular mechanisms by which IAV disrupts critical alveolar function leading to fatal ALI, and to establish restoration of AWL secretion â€Â"" that is, “AWL rescue” â€Â"" as a new therapeutic approach for ALI caused by IAV-SA coinfection. Therefore, this proposal addresses the NHLBI mission.",,2027,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,485947,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2022 +P22908,75N93023C00031-0-9999-1,MULTIVALENT QS-18 PROTEIN NANOPARTICLES FOR A BROADLY PROTECTIVE INFLUENZA VIRUS VACCINE,"The COVID-19 pandemic has underscored the importance of not only vaccines but also vaccine adjuvants. Plant saponins have yielded some of the most powerful vaccine adjuvants to date. This project seeks to combine and develop QS-18, a commercially viable and highly abundant saponin, with spontaneous nanoliposome antigen particlization technology based on cobalt porphyrin-phospholipid (CoPoP), which has demonstrated its clinical application and entered Phase III clinical trials. Influenza will be used as a model disease to study the advantages of QS-18. The project will provide pilot data necessary to clinical translation focused on toxicity (mouse and rabbits) and efficacy (mouse and ferrets) through the following objectives: (1) Produce and procure well-characterized CoPoP/QS-18 liposomes, displaying influenza hemagglutinin (HA) and neuraminidase (NA) antigens; (2) Characterize concentration of components of CoPoP/QS-18 liposomes; (3) Determine storage stability of components of CoPoP/QS-18 liposomes; (4) Determine pilot toxicity of CoPoP/QS-18 liposomes and CoPoP/QS-21 liposomes; (5) Compare CoPoP/QS-18 to CoPoP/QS-21 for inducing antigen-specific antibodies and antigen specific cellular responses following mouse immunization; (6) Assess how CoPoP/QS-18 induces protective immune responses in a mouse challenge using mouse adapted H1, H3, and B influenza virus strains; (7) Assess protection from influenza virus challenge in ferrets.",,2025,"POP BIOTECHNOLOGIES, INC",599806,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3 | Other,Unspecified,,Unspecified,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2023 +P22909,5U01AI150747-04,DYNAMICS AND EVOLUTION OF IMMUNE RESPONSES TO INFLUENZA VIRUSES,"PROJECT SUMMARY/ABSTRACT Our goal is to develop a quantitative framework for the generation, boosting and maintenance of immunological memory. Mathematical models are useful because immunization and infection involve the interaction of rapidly changing populations of virus and multiple populations of immune cells. We first develop and validate models using experiments in mice. We then use these validated models to analyze data from human vaccination studies. Aim 1 asks how prior immunity affects and potentially limit the boosting of immunity and apply this to influenza. Our approach is to develop models to understand why prior immunity limits boosting of antibodies to conserved regions of the virus. Specifically, we use our models to better understand how prior immunity might limit boosting of antibody responses to conserved regions on the stem of the hemagglutinin molecule that is the focus of universal influenza vaccines. Aim 2 considers the factors that affect the durability of humoral immune memory, and address questions such as why memory generated by immunization with protein antigens is less durable than immunity generated by virus infection, and how prior immunity can differentially affect the boosting and generation of memory to new strains of influenza. Aim 3 considers the generation of CD8 T cell memory to influenza and yellow fever. We will determine how repeated exposure to influenza affects the diversity of the CD8 T cell responses generated. We have access to a unique dataset that follows the number of YFV-specific CD8 T cells, changes in their phenotype, and their turnover from heavy water labelling studies for a period of over one year. Our analysis of this dataset will allow us to address an ongoing controversy regarding whether are long-term memory CD8 memory stem cells are generated rapidly after immunization or only gradually over time. Aim 4 describes computational tools that we will build for B cell receptor sequence analysis and visualization, and for simulation of the dynamics of immune responses. These tools will be widely accessible online, and promoted at workshops and scientific symposia we organize.",,2025,EMORY UNIVERSITY,1146012,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +P22912,5U01IP001136-03,Modeling toolkit to evaluate multifaceted control strategies for seasonal and pandemic influenza,"PROJECT SUMMARY We will develop a data-driven model of seasonal and pandemic influenza transmission throughout the US to accelerate robust assessments of multifaceted influenza intervention strategies. We will work closely with the CDC Modeling Network to advance the fidelity, transparency and translation of models as an evidence base for influenza policy making, prevention and control. This project extends a metapopulation model of influenza transmission within and between 217 major metropolitan areas in the US that we are developing in collaboration with the CDC Modeling Network. The model includes travel between cities, age- and risk-group specific susceptibility, probability of clinical outcomes, intervention efficacies and uptake rates, as well as the impacts of local climate and school calendars on transmission rates. Using a range of public health, epidemiological, societal and economic metrics, the model can flexibly evaluate thousands of candidate intervention strategies, including time- and location-based combinations of vaccines, antivirals, and social distancing measures with potential subgroup-specific prioritization. Our proposal includes four major aims. In Aim 1, we will extend our US Influenza Model to include the co- circulation of multiple viruses competing via transient heterosubtypic immunity. We will derive new estimates for the duration and magnitude of heterosubtypic immunity and design strain-specific strategies for effectively controlling co-circulating seasonal and pandemic influenza viruses. In Aim 2, we will evaluate intervention strategies that leverage newly approved and combined antiviral drugs. We will fit within-host viral dynamic models to clinical data on new antivirals to estimate the efficacy of various drug regimens in different subpopulations with respect to disease severity, infectiousness, and the risk of antiviral resistance. In Aim 3, we will build a granular within-city model of influenza transmission based on abundant data and local collaborations with public health and healthcare leaders in the Austin-Round Rock Metropolitan Area. We will apply the model to elucidate socioeconomic and geographic disparities in influenza risk and design interventions that ameliorate such gaps. In Aim 4, we will build an interactive visualization platform that allows users to specify epidemic scenarios, implement layered interventions as simulations unfold, and view the model dynamics through the lens of a surveillance module based on the CDC’s FluView Interactive portal. We will work extensively with the CDC Modeling Network to build a diverse portfolio of validated models and best practices for collaborative decision support. Our projects will contribute flexible models for the evaluation of multifaceted influenza interventions, elucidate competition among influenza viruses and the efficacies of novel antivirals, and provide insights into socioeconomic disparities in influenza burden. Furthermore, our innovative visualization tool will broadly support the translation of science to public policy.",,2025,University Of Texas At Austin,738730,Other,Unspecified,Unspecified,Urban Population/Setting | Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Research to inform ethical issues,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Research to inform ethical issues related to Public Health Measures,2020 +P22913,7R01AI139063-05,Visualization of Influenza Viral RNA Assembly,"Influenza A viruses (IAV) pose a major public health threat through both seasonal epidemics and sporadic pandemics. The segmented nature of the viral genome promotes reassortment, a process where the genetic material between viruses is exchanged in a co-Ã'­infected cell. In nature, reassortment leads to increased viral diversity and emergence of pandemic influenza viruses. For example, the 2009 influenza H1N1 (‘swine flu’) pandemic virus, emerged from reassortment of two circulating swine viruses. Prediction of future pandemic influenza viruses from circulating zoonotic virus populations is difficult because very little is known about the mechanism of reassortment within a single co-infected cell. To accurately define the process of reassortment, we must first understand the dynamics of intracellular viral RNA (vRNA) assembly. Influenza vRNA replicates in the nucleus and is transported to the plasma membrane for packaging, which requires one copy of all eight segments to assemble within a single virion to produce a fully infectious virus. In this proposal, we will build upon our previous data on influenza assembly and define 1) the assembly dynamics in physiologically relevant human and swine cell types, 2) the cellular proteins modulating vRNA transport, and 3) the location of reassortment within a co-Ã'­infected cell. Our central hypothesis is that vRNA assembly occurs in a cell-Ã'­type specific manner that correlates with IAV reassortment in different host species. The Specific Aims of this application will use a variety of sophisticated microscopy tools, including live cell imaging with a custom light-Ã'­sheet microscope, to determine the assembly mechanism in various cell culture models. Aim 1 will utilize multicolor fluorescent in situ hybridization and live cell imaging techniques to explore the dynamics of influenza vRNA assembly in human and swine differentiated airway epithelial cells. Aim 2 will uncover the identity and roles of cellular cytoskeletal proteins and membranous organelles utilized during influenza vRNA assembly using biochemical approaches like proximity-Ã'­dependent biotinylation. Aim 3 will combine imaging and genomic approaches to characterize the cellular location of vRNA intermingling during co-infection with two heterologous viruses in differentiated airway epithelial cells. The proposed work will address many outstanding questions in influenza biology regarding reassortment that have remained unanswered due to a lack of tools to track vRNA movement in live cells during a productive infection. In addition, these studies will identify novel host factors involved in vRNA packaging that can be pursued as potential therapeutic targets.",,2024,Emory University,381589,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P22914,5R21AI153882-02,Mathematical Modeling of Influenza Severity in Outbred Mice,"PROJECT SUMMARY In the United States, pulmonary influenza infection occurs annually in 5-20% of the population with mortality in the range of 30,000 deaths. The recent 2009 influenza H1N1 pandemic illustrated the potential for higher infection rates, which were reported to be as high as 45% in certain age groups. The 2017-18 influenza season had the highest pediatric mortalities since the 2009 pandemic. Influenza infection is known to result in a broad spectrum of disease phenotypes in humans, although severe pneumonia is relatively rare. Despite this, severe disease often requires advanced supportive care in the young, including previously healthy children. Host factors involved in determining the outcome of influenza infection are unclear and children are known to be at higher risk of severe disease. First life exposure to influenza is also thought to dictate life-long immunity. Little is known about the effects of young age and gender on influenza responses and severity. This underscores the importance of understanding influenza pathogenesis in a pediatric population. Influenza pathogenesis is likely mediated in large part by exuberant inflammatory host responses in the lung. It is likely that predictive soluble inflammatory mediators are present in severe infection. Further, predictive biomarkers or mathematical models of influenza pneumonia severity would enhance clinical decision making and patient care. We propose that machine learning and mathematical modeling of host immune endpoints will define a molecular fingerprint of severe influenza pneumonia in juveniles. This hypothesis will be tested in two Aims. Aim 1 will focus on characteristic molecular pathways related to influenza severity in juvenile animals, using outbred mice. We will utilize machine learning and new mathematical approaches for pathway and biomarker selection. Aim 2 will test mathematical models of influenza pathogenesis to elucidate new mechanisms that drive lung injury. The overall goal of the proposed study is to identify novel biomarkers and mechanistic models of influenza pneumonia severity that can be applied to children. To accomplish this we will use a broad, exploratory, and unbiased approach. Candidate biomarkers and pathways would then be evaluated in future mechanistic and translational studies in mice and humans.",,2023,University Of Pittsburgh At Pittsburgh,189830,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease susceptibility",2020 +P22915,3UM1AI148576-03S5,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2023,Emory University,4699209,Not applicable,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Disease X | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22916,5U01IP001141-03,Individual-based Simulation of Seasonal and Pandemic Influenza Epidemics - supplement Emergency Response to the COVID-19 Pandemic,"Project Abstract Seasonal influenza caused an estimated 48.8 million illnesses, 22.7 million health care visits, 959,000 hospitalizations, and 79,400 deaths in 2017-18. Influenza is a particularly complicated disease to prevent as the influenza virus itself changes over time, and unlike vaccinations for measles or hepatitis B, the effectiveness of annual vaccination may be limited if the particular strain that appears in an outbreak is not represented in the vaccine. In addition, the immunity produced by vaccination declines over time, and many individuals, especially the elderly, may lose protection toward the end of an influenza season. The goals of iMPH: Influenza Modeling for Public Health are to bring together four experienced modeling groups including the Public Health Dynamics Laboratory (PHDL) that has significant experience as a MIDAS Center of Excellence in the agent-based modeling of influenza, the Pittsburgh Vaccine Research Group (PittVax), vaccine policy experts who are site leads in both the inpatient and outpatient CDC influenza vaccine effectiveness (VE) networks, the DELPHI (Developing the Theory and Practice of Epidemiological Forecasting) group at CMU, the most accurate US influenza prediction group, and the current MIDAS Network Coordination Center (MCC) that brings major data and model coordination expertise. Our specific Aims are to create realistic, biologically based models of influenza, including the development and maintenance of immunity over time through either the development of the disease or vaccination so that we can test the benefit of different prevention strategies in seasonal or pandemic influenza. Specifically, we will examine strategies such as: enhanced vaccines that create high initial antibody levels, the addition of a second, mid-season vaccine, or potentially delaying vaccination in some individuals until later in the season. We will also examine the effectiveness of vaccination policies over a multi-year time, such as different vaccinations for individuals who have had previous influenza, and consideration of every-other year vaccines, Finally we will examine community-level interventions, such as school closures and working from home to impact the spread of influenza over a season. As a CDC Influenza Modeling Center, we will also collaborate with other centers to develop rapid responses to current influenza threats, to share data, models and results to provide higher confidence to the CDC that model-based recommendations can be used to formulate local, state and national influenza policy.",,2025,University Of Pittsburgh At Pittsburgh,750000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Immunity | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P22917,3UM1AI148576-03S2,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2022,Emory University,127192,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22918,3UM1AI148576-03S4,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2023,Emory University,518350,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22919,3UM1AI148576-03S3,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2023,Emory University,318891,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22920,3UM1AI148576-03S6,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2023,Emory University,3175510,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2022 +P22921,3UM1AI148576-03S1,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2024,Emory University,101118,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22922,1R43IP001228-01,"PA-21-259, SBIR, Phase I, Self-Amplifying RNA Replicon-Based Platform for Generating Multivalent Influenza Vaccine","PROJECT ABSTRACT Current vaccines are mainly strain-specific and have limited efficacy in preventing new, potentially pandemic influenza strains. Interest in a universal influenza vaccine (UIV) to prevent future pandemics has been greatly boosted by the success of mRNA-based coronavirus vaccines. However, developing a UIV has been particularly challenging for two reasons: (1) the failure of immunization to induce broadly neutralizing antibodies against conserved epitopes and (2) the lack of a safe and effective vaccine platform to induce broad and long-lasting immunity. Virus-like vesicles (VLVs) are infectious, self-propagating alphavirus-vesiculovirus hybrid vaccine vectors that can be engineered to express foreign antigens to elicit a protective immune response. These self-amplifying RNA replicons are safe, highly immunogenic, and scalable to produce. The goal of this proposal is to rationally design and engineer a VLV to express multiple flu antigens and thus induce broad and long-lasting immunity. As shown in our published studies, the ectodomain of M2 (M2e) and domains of the immunodominant hemagglutinin (HA) globular head can elicit robust antibody responses that mitigate disease and protect mice from lethal challenge. We have also established that VLV carrying RNA encoding one or more of the major antigens of hepatitis B virus (HBV) in a single open reading frame drives a broad multi-specific immune response that results in substantial clearance of HBV in the mouse liver. Recent improvements in the development of this VLV immunotherapy vector enhanced gene expression with a concomitant increase in both T-cell responses and antibodies. In preliminary studies, we found that signal sequences promote efficient secretion of recombinant proteins that are highly conserved among influenza strains, i.e., M2e, nucleoprotein, the long-alpha helix (LAH) of subunit 2 of HA, and fusion peptide from VLV-infected cells. Our initial single-dose screening of individual flu antigen VLV vaccines (sponsored by the Respiratory Diseases Branch of NIAID/NIH) showed promising mitigation of disease progression. A reduction in lung virus titer was apparent in HA2 VLV vaccines. Albeit low, viral neutralizing titers (VNTs) were present in all immunized groups (>1:16). In addition, our serological data show an increased induction of IgG1 and IgG2a in most flu-based VLV-immunized groups. These virus-specific IgG isotypes correlate better with vaccine efficacy than neutralization alone. We will carry out three specific aims: Aim 1. Characterize the immunogenicity of VLV-Multi-Ag constructs in mice. Aim 2. Evaluate vaccine efficacy in a lethal influenza mouse model. Aim 3. Evaluate prime-boost regimens to optimize flu-specific immune responses. The results of these studies will provide initial data on the feasibility of developing a UIV. VLV-mediated delivery of multi-antigens targeting multiple epitopes of conserved proteins may provide an effective strategy to prevent infection with influenza virus. The proposed research is highly significant because an effective vaccine is needed to prevent both influenza epidemics and to enhance our ability to respond to future pandemics.",,2024,CAROGEN CORPORATION,263991,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2023 +P22923,5U01IP001137-03,FluMod - Center for the Multiscale Modeling of Pandemic and seasonal Flu Prevention and Control,"PROJECT SUMMARY In this proposal we plan to contribute addressing the above foundational and operational challenges by advancing the science of influenza modeling and contributing novel methods and data sources that will increase the accuracy and availability of seasonal and pandemic influenza models. To address these challenges, we plan to build on the unique mechanistic spatially structured modeling approaches developed by our consortium, that includes stochastic metapopulation models and fully developed agent-based models nested together in our global epidemic and mobility modeling (GLEAM) approach. The objective of this project is to generate novel and actionable scientific insights from dynamic transmission models of influenza transmission that effectively integrate key socio-demographic indicators of the focus population, as well as a wide spectrum of pharmaceutical and non-pharmaceutical interventions. Our proposed work in specific aim 1 (A1) will leverage our global modeling (from the global to local scale) framework that can be used to explore the multi-year impact of influenza vaccination, antiviral prophylaxis/treatment, and community mitigation during influenza seasons and pandemics. Our specific aim 2 (A2) will focus on using high quality data to model heterogeneous transmission drivers and novel contact pattern stratifications that will allow us to guide mitigation strategies and prioritization for interventions. In our Aim 3 (A3) we will use artificial intelligence approaches to identify interventions that are particularly synergistic and well-suited to particular epidemic scenarios, for seasonal and pandemic influenza. Our overarching goal is to provide a modeling portfolio with flexible and innovative mathematical and computational approaches. We aim to address several questions commonly asked about seasonal and pandemic influenza and match these with analytical methods and outbreak projections. The modeling and data developed in this project can help facilitate and justify transparent public health decisions, while contributing to the definition of standard methods for model selection and validation. Finally, our influenza modeling platform can also benefit the broader network of modeling teams and can be used to improve result sharing and harmonization of modeling approaches.",,2025,Northeastern University,750000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P22924,1R01AI158484-01A1,Role of preexisting immunity on airborne transmission of influenza viruses,"SUMMARY: Role of Pre-existing Immunity on Airborne Transmission of Influenza A Viruses Influenza viruses pose a major public health threat through both seasonal epidemics and sporadic pandemics. The epidemiological success of influenza viruses relies on its ability to spread efficiently through the air and navigate three distinct spaces: 1) the donor, 2) the environment and 3) the recipient (Lakdawala and Subbarao Nature Medicine 2012). The first infection with influenza viruses leaves a long-lasting immunity, which can be evaded by the virus through antigenic drift and shift. Our published data using the ferret model shows that pre-existing immunity from the 2009 H1N1 pandemic virus infection protects recipient animals from airborne transmission of a seasonal H3N2 influenza virus (Le Sage et al PLoS Pathogens 2021). We hypothesize that pre-existing immunity can influence susceptibility to circulating influenza strains independent of neutralizing antibody. To understand the role of pre-existing immunity in protection against airborne transmission, Aim 1 will identify immunological and viral factors underlying susceptibility to airborne transmission. Each influenza season, population-wide immunity triggers viral antigenic evolution, Aim 2 will determine the impact of antigenic drift on the susceptibility to influenza virus transmission. Aim 3 will examine the impact of different vaccine platforms on susceptibility to drifted influenza virus strains. This proposal will provide a better understanding of the immune protection needed to dampen influenza virus transmission and inform effective universal vaccine strategies.",,2023,University Of Pittsburgh At Pittsburgh,644203,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,H3,,,H3N2,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2022 +P22925,5R01AI154894-03,Role of spatial structure in shaping viral population diversity and evolution,"Summary Viral evolution enables the emergence of novel viral pathogens in the human population. The evolution of influenza A virus is also critical for the maintenance of seasonal lineages in the context of host immunity. Evolution can result from selection, leading to increased fitness, or stochastic processes that typically decrease fitness. The relative potency of selective and stochastic forces is therefore a critical determinant of the adaptive potential of a population. Based on evolutionary theory, we hypothesize that the magnitude of stochastic effects in viral evolution is strongly impacted by the spatial structure that characterizes viral spread within a host. In other words, the expansion of a virus population in space may give rise to random, within-host bottlenecks and founder effects that weaken the efficiency of natural selection. Factors that shape viral spread - including viral phenotypes, host responses and physical characteristics of the host environment - are therefore predicted to impact viral genetic diversity and evolution. Our overarching hypothesis is that viral features that modulate viral spatial structure also modulate viral diversity and evolution. We will test this hypothesis for influenza A virus using a well-integrated combination of simulation modeling and experimental approaches. In Aim 1, we will use computational, cell culture and ferret models to examine the consequences of spatially structured spread for genetic diversity of viral populations. For our experiments, we will use viruses carrying a selectively neutral barcode to allow robust quantification of viral diversity. In this way, the degree to which stochastic effects dominate viral dynamics will be examined under a range of conditions. In Aim 2, we will evaluate the consequences of spatially structured spread for both purifying and positive selection. Computational approaches will be used to develop hypotheses of how long distance virus dispersal impacts the ability of de novo beneficial and deleterious mutations to reach dominance. These model predictions will then be tested using experimental evolution under conditions of common vs. rare long distance dispersal. In this way, we will test the theoretical concept that stochastic effects associated with spatial structure impede the ability of natural selection to act on expanding populations. Taken together, the research proposed in these two aims will uncover the importance of spatial structure to viral population biology and evolution, deepening our fundamental understanding of the forces shaping viral evolution in nature.",,2025,Emory University,559622,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P22926,5R01AI150885-02,High-throughput assays and small-molecule discovery of antiviral candidates targeting influenza hemagglutinin,"PROJECT SUMMARY / ABSTRACT Influenza A viruses exhibit extreme diversity as exemplified by the multiple serotypes of the hemagglutinin (HA, H1-H18) and neuraminidase (NA, N1-N11) surface antigens. To date, only 3 of 198 possible combinations of HA and NA in avian and other animal reservoirs have been associated with human pandemics (H1N1, H2N2, H3N2). Recent appearances of H5N1, H6N1, H7N7, H7N9, H9N2, and H10N8 in humans are constant reminders of the potential for devastating new pandemics. Influenza B viruses with its two lineages further increase the health and economic burdens of seasonal influenza. No effective antiviral drugs are currently available for preventing entry of influenza A or B viruses into host cells (scientific premise). However, relatively recent discoveries of broadly neutralizing antibodies to human influenza viruses and concomitant structural studies have identified sites-of-vulnerability on the HA in pandemic, seasonal, and emerging influenza viruses. These HA surface sites include the receptor binding site and membrane-proximal stem housing the fusion machinery, both of which are essential for cellular infection. Common features for recognition of these sites can now be exploited in design of small molecules to ultimately develop broadly applicable influenza antivirals. Here, we will employ this structural information into the optimization and execution of high-throughput assays to identify new small-molecule scaffolds that target the highly conserved and vulnerable stem-binding site. High- throughput screening will be performed in parallel on representative HAs from influenza A group 1 against 600K structurally diverse molecules (SA1). We will also subject group 2 and influenza B HAs to a 300K compound screen (SA2). Validated hit compounds will be prioritized based on affinity and breadth across HAs and top candidates will be rigorously optimized into lead molecules by x-ray structure-based design cycled with medicinal chemistry. Biophysical binding, cellular infectivity and resistance assays (e.g., combinatorial viral libraries of HA mutants) will aid in iterative design, selection, and characterization of potential novel therapeutic candidates with favorable drug-like properties. All of these methods are actively employed in the Wolan and Wilson laboratories. As proof-of-concept for this approach, we identified a molecule with modest affinity to the stem of group 1 HAs with an HT assay of our own design. Its co-crystal structure with HA provided critical information towards design and synthesis of a focused compound library, which we used to produce a stereoselective molecule with nanomolar affinity and antiviral activity. Our overall goal is to identify and improve molecules with broad potency against the stem of groups 1 and 2 as well as flu B HAs. To our knowledge, we are the first to design an assay against group 2 and flu B HAs amenable to HTS (innovation). We anticipate that several classes of stem-targeted compound scaffolds will be identified with nanomolar affinity to HAs with cellular antiviral activity and suitable PK-ADME properties. Future efforts will include animal models of influenza infections to further validate our antivirals with the ultimate goal of combatting future influenza pandemics and seasonal epidemics.",,2025,"SCRIPPS RESEARCH INSTITUTE, THE",678526,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22927,5R01AI147109-03,Rapid Manufacturing of a Universal Flu Vaccine Using TMV-conjugated Centralized Antigens,"Project Abstract This interdisciplinary proposal brings together three highly successful but independent technologies to create an effective and broadly neutralizing universal influenza vaccine. Our approach combines breath of immunity, by using a consensus HA strategy, production speed and capacity by working with Kentucky BioProcessing (KBP), who can express HA protein in plants, and vastly improved subunit vaccine potency using a TMV-HA conjugation approach to create a candidate universal influenza virus vaccine. Based on our preclinical data on three influenza A strains, we expect our approach will drive long term immunity that is balanced between antibody and cellular immunity, providing potential for overlapping mechanisms of immune protection. We bring together a strong team of different disciplines with a combined goal to quickly show proof of concept with H1, H3, H5, and M2e antigens. Our Specific Aims are as follows: 1) Production of TMV-HA conjugates of centralized H1, H3, H5 genes and M2e peptide, 2) Immune response analysis, murine challenge studies and 3) Translational and ferret studies of TMV-HAc and TMV-M2e vaccines. Dr. Weaver has developed a computational method to express an ancestral sequence of HA, representing a consensus of sequences within an Influenza subtype. These vaccines protect against drifted seasonal influenza variants better than a traditional trivalent inactivated virus vaccine. In partnership with KBP, we will use established plant expression methods to produce centralized HA proteins, with the capacity to produce protein for the planned studies and for future clinical trial development. HA consensus protein will be fused to the surface of Tobacco Mosaic virus (TMV) by chemical conjugation, a method developed by Dr. McCormick to improve HA subunit vaccine potency. TMV-HA vaccines will also be combined with a highly conserved M2e peptide vaccine, to broaden protection and reduce vaccine dose. Immunological analysis will be used to confirm vaccine potency, in order to optimize dose, schedule and route of administration. Vaccine efficacy and broadly protective immunity will be confirmed by lethal influenza challenge using 9 divergent virus types in a murine model of disease. Finally, vaccine formulations will be re-tested in ferrets, a models of influenza infection which more closely mimics the progress of disease in humans. Our vaccine is designed to drive local and systemic immunity after either intranasal or intramuscular routes of administration, and we will use immunogenicity and pathogen challenge data to define an optimized single dose vaccine formulation. Our goal is to generate an effective universal vaccine against influenza that can be manufactured at scale, with significant potential for translation into a universal vaccine product that is ready for clinical testing.",,2025,UNIVERSITY OF NEBRASKA LINCOLN,619095,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3 | H5,Unspecified,,Unspecified,Unspecified,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22928,3UM1AI148452-03S1,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2023,Vanderbilt University Medical Center,592422,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22929,3UM1AI148452-03S2,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2023,Vanderbilt University Medical Center,303464,Human Populations | Viruses,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22930,3UM1AI148452-03S3,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2023,Vanderbilt University Medical Center,13319092,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22931,3UM1AI148452-03S4,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2023,Vanderbilt University Medical Center,2059956,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2022 +P22932,1R43AI170395-01,"Development of a single-dose self-amplifying RNA vaccine for boosting pre-existing influenza virus immunity, driving B and T cell responses to conserved targets","Project Summary While a universal influenza vaccine, providing life-long protective immunity against all current and future drifted and shifted subtypes of influenza virus after 2 or 3 doses, would be a game-changing solution to reducing the global burden of influenza and its associated morbidity and mortality, other approaches to solving this problem are urgently needed. There is still much to learn about immune responses to respiratory pathogens, such as influenza virus, and vaccine approaches that drive life-long immunity to respiratory viruses have yet to be demonstrated in humans. Therefore, we propose to develop a broadly protective influenza booster vaccine that can be administered, either seasonally or during pandemics, to individuals with prior exposures to either natural infection or seasonal vaccination. Given the non-uniform influenza immune history in a given population of individuals, it is likely that booster vaccines will need to be customized either at the individual or regional level, based on local influenza virus epidemiology or vaccine uptake. Nucleic acid vaccine platforms provide the ideal framework for such personalized-medicine approaches, due to the flexibility of development, as typified by the ongoing COVID-19 pandemic. As proof-of-concept, here we propose to apply our clinical-stage replicating RNA vaccine platform to develop a booster vaccine targeting the conserved hemagglutinin stem and nucleoprotein of group 1 influenza viruses and evaluating immunogenicity and efficacy against heterologous group 1 influenza virus infections in mouse and ferret models of pre-existing influenza virus immunity. These data will inform the feasibility of such an approach and characterize what types of pre-existing immunity, in terms of anti-hemagglutinin antibody specificity and magnitude, are required for booster vaccine efficacy. As these pre-existing antibody criteria are easily assessed in humans, it is likely that a personalized approach to influenza booster vaccination is achievable.",,2024,HDT BIO CORPORATION,104692,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Characterisation of vaccine-induced immunity,2022 +P22934,1U01IP001189-01,"Component A _ Credible Effectiveness Measures of Seasonal Influenza, COVID-19 and Other Respiratory Virus Vaccines against Ambulatory Care for Acute Illness in Texas (and Component D).","COMPONENT A - PROJECT SUMMARY/ABSTRACT: Influenza (Flu) viruses are constantly evolving, requiring vaccines to be reformulated every season. New SARS- CoV-2 (SC2) variants have caused recurrent Coronavirus Infectious Disease â€Â"" 2019 (COVID) surges in different regions of the United States through the winter of 2021-22. Estimating ongoing real-world Flu and COVID vaccine effectiveness (VE) against ambulatory care for acute illness (ACAI) are essential in evaluating the protection provided by nationwide vaccination programs and for monitoring the duration of protection afforded by respective vaccines each of which are high priorities for fulfilling the CDC’s mission of serving as the nation’s health protection agency. Our long-term research goal is to advance the understanding of the epidemiology and prevention of respiratory virus (RV) infections (i.e., seasonal and pandemic influenza, SC2 and Other Respiratory Viruses (ORVs) such as Respiratory Syncytial Virus [RSV]) while reducing the burden of disease and improving the health of the population. We plan to systematically evaluate the VE against ACAI associated with lab-confirmed influenza, COVID and vaccine-preventable ORVs with respective CDC recommended vaccinations in the Baylor Scott & White Health, Central Texas (BSWCTX) enrollment eligible population. The objective is to obtain reliable vaccination information and to provide accurate interim and annual estimates of VE to prevent ACAI in respective RV vaccine age-eligible population. Our central hypothesis is that timely and accurate measurement of VE and burden of illness due to vaccine preventable RVs is sustainable. The rationale is that by assessing the interim and annual VE against vaccine preventable RVs, the CDC ACIP can modify recommendations for receiving the vaccines and booster doses as well as use of appropriate antiviral agents. The specific aims are to: 1) Measure effectiveness of seasonal and pandemic Flu, COVID and vaccine-preventable ORV vaccines against ACAI for respective lab-confirmed mild to moderate infection in at least 1,000 children and adults from the 2022-23 to 2026-27 seasons. 2) Monitor ongoing Flu and SC2 viral evolution by genomic sequencing among at least 1,000 enrolled children and adults from the 2022-23 to 2026-27 seasons. 3) Perform potentially year-round SC2 surveillance during periods when Flu viruses are not circulating to measure current COVID VE against ACAI for lab-confirmed mild to moderate SC2 infection in children and adults from the 2022-23 to 2026-27 seasons. To accomplish these aims, we will estimate real-time VE in the ambulatory setting using a test-negative design, estimate burden of illness of vaccine preventable RVs in the BSWCTX burden subset, and examine factors affecting VE. The proposed research is innovative as we have adapted methods to include verified vaccinations and accurate lab diagnosis of RV infections with one or both influenza and SC2 in participants who are systematically screened for eligibility and enrolled using a well-defined ACAI case-definition in our approach, enabling us to aptly measure VE and burden of illness of influenza, COVID, and ORVs in the West South Central United States.",,2027,BAYLOR RESEARCH INSTITUTE,2000000,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Impact/ effectiveness of control measures | Disease surveillance & mapping | Characterisation of vaccine-induced immunity",2022 +P22935,4R42AI155039-02,Development of 4-(aroylamino)piperidine-based entry inhibitors as anti-influenza therapeutics,"Influenza A viruses belong to the orthomyxoviridae family, and have a negative-sense, segmented RNA genome, which can cause seasonal or pandemic flu with high morbidity and significant mortality. Vaccination is the most prevalent prophylactic means for controlling influenza infections. However, an effective vaccine usually takes at least six months to develop. Furthermore, vaccination has limited effectiveness in the treatment of immunocompromised patients, and its effectiveness is also limited during a pandemic. The current therapeutic options for flu infections are all based on the neuraminidase inhibitors (NAIs; oseltamivir, zanamivir and peramivir), while the influenza M2 ion channel blockers (amantadine and rimantadine) are not now recommended since all of the circulating influenza strains have acquired resistance. (Xofluza, a polymerase acidic endonuclease inhibitor, has just been approved in 2018 and is yet untried during a flu season.) The rapid emergence of the NAI-resistant strains of influenza A viruses strongly suggests that NAIs alone may not be sufficient as effective therapies, and thus new treatment options targeting the other viral/host factors are urgently needed. This application defines a plan to develop potent, small molecule inhibitors, which block entry of influenza A viruses. We have identified compounds that inhibit entry of infectious influenza A viruses, with IC50 values in the nanomolar range. We have synthesized structurally diverse analogs of the anti-influenza hit series using structure-activity relationships (SARs) to improve potency and selectivity; validated the lead inhibitor candidates in the infectious assay and investigated the mechanism of action (MOA) of the these inhibitors; and selected anti-influenza inhibitors with excellent in vitro potency and selectivity values and druglike in vivo pharmacokinetic properties. In this Fast Track STTR Phase I &II application, we propose four specific aims: (1) optimize the lead scaffold and select development candidates; (2) investigate the mechanism of action (MOA) of the advanced lead compounds with HA proteins; (3) evaluate the pharmacokinetics/toxicokinetics of the advanced lead compounds; and (4) preclinical development.",,2025,"CHICAGO BIOSOLUTIONS, INC.",999369,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22936,5U01EB029085-05,A Microphysiological Mimicry of Human Lung-Bone Marrow Organ-Organ Crosstalk On-a-Chip,"PROJECT SUMMARY. Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 20 years. Influenza A viruses (IAVs) comprise 50% of the emerging respiratory viruses and can cause substantial morbidity and mortality. IAVs can infect a diversity of avian and mammalian species, including humans, and have the remarkable capacity to evolve and adapt to new hosts. Despite the tremendous progress made in virology and epidemiology, which subtype or strain of IAV will cause the next outbreak remains unpredictable. Importantly, there is no clinically simulating, pathophysiologically relevant, and readily available in vitro multi-organ system for predicting the pathogenicity of emerging and re-emerging influenza viruses in humans. Recent compelling evidence have revealed opposing roles for two major classes of bone marrow (BM)-produced innate immune cells in shaping the outcome of IAV infection, with neutrophils offering protection and increase in circulating monocytes being associated with increased pathology. Thus, selective mobilization of either of these two distinct cell types in response to pulmonary infection with IAV can indirectly reveal potential pathogenicity of a given viral strain. The overarching goal of this project is to develop a highly innovative, reductionist, yet advanced and complex, physiologically relevant in vitro model of influenza infection in humans utilizing Organ-on-Chip technology in order to predict virulence and infectivity of different IAV strains, by reproducing clinically and in vivo-observed immunological correlates of infection severity. More specifically, we will engineer a first-in-kind fluidically integrated multi- organ system that recreates BM-lung axis, using primary human-derived cells, for real-time analysis of inflammation and leukocyte mobilization in response to influenza challenge. Our central hypothesis is that this dynamic living microsystem can recapitulate differential immune cell mobilization and tissue pathology in response to high-pathogenicity vs. low-pathogenicity IAV infections in vitro. To address the hypothesis, we propose the following specific aims: (1) to engineer a living and hematopoietically active human BM-on-a-Chip and microfluidically link it to a human Lung Small Airway-on-a-Chip that our team has previously developed and characterize homeostatic physiology and organ-organ crosstalk; and (3) to challenge the BM-Lung microsystem with airborne IAVs under rhythmic breathing and reproduce differential leukocyte mobilization and tissue damage in response to distinctly pathogenic viral strains. Such a novel platform holds great potential in emulating and predicting pathogenicity of IAVs (e.g., during outbreaks, pandemics or when presence of a highly virulent strain is speculated), utilizing human cells isolated from desired donor/patient populations, and without needing to adapt the virus for host (as required for some animal studies). In addition, it can considerably accelerate drug development studies by enabling personalized drug efficacy testing and identification of new therapeutic targets.",,2024,University Of Pittsburgh At Pittsburgh,389087,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2021 +P22937,5R21AI153812-02,Human Genetic Variation Regulating Transcriptional Response and Cellular Susceptibility to Influenza,"Project Summary/Abstract It is estimated that 50-100 million people (~5% of the global population) died from the 1918 influenza pandemic. While influenza infections usually do not cause such severe disease, ~30 million are infected every year in the United States alone (2014-2015). However, there are broad differences in influenza susceptibility and severity, with outcomes from asymptomatic infections (~16%) to death (0.2% in 2014-2015). These differences arise from the complex interplay of exposure, environment, influenza genetics, and human genetics. The overall goal of my lab is to understand how human genetic diversity regulates susceptibility and severity of infections. Famous examples of genetic differences that profoundly impact susceptibility include sickle cell allele protection against malaria and CCR5 deletion protection against HIV. Such genetic differences can lead to insights on pathogenesis, drug targets (e.g. CCR5 inhibitors), and more personalized care. For influenza, common genetic variation has been most convincingly shown to influence flu severity at a single locus (IFITM3) that regulates a single step (cytosolic entry) in the complex influenza life cycle. We hypothesize that other human genetic differences affect influenza infection and can be identified through measuring inter-individual variation in cellular infection phenotypes. To facilitate identification of SNPs that affect cellular infection phenotypes, we developed and validated a cell-based GWAS approach called Hi-HOST. SNPs identified as important for influenza infection by Hi-HOST can then be examined for relevance in human infection using already completed human flu challenge studies and population-based studies. We propose that the intersection of human subject and cell line data facilitates discovery of novel pathways and genetic determinants of susceptibility. This project will generate a high resolution analysis of how human genetic variants impact transcription, cellular phenotypes, and human disease following influenza exposure. We will accomplish this through 1) identifying human SNPs that confer resistance/susceptibility to cellular and molecular phenotypes of flu infection, including entry, replication, cell death, cytokine levels, and host transcriptional responses, 2) determining the impact of SNPs on host transcription during influenza challenge of healthy volunteers, and 3) integrating the generated cellular and human challenge datasets to generate and test hypotheses linking transcriptional response and cellular susceptibility. Understanding these differences could lead to new diagnostic approaches in identifying at-risk individuals and novel therapeutic strategies for treatment.",,2023,Duke University,235610,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22938,1R01AI170089-01,Genetic Contributors to the Impact of Sex on Heterogeneity in Flu Infection,"Project Summary/Abstract The 1918 influenza pandemic is estimated to have killed 1 in 20 people worldwide. Influenza A virus (IAV) infections usually do not cause such severe disease for the ~30 million infected every year in the United States alone (2014-2015). However, there are broad differences in IAV susceptibility and severity, with outcomes from asymptomatic infections (~16%) to death (0.2% in 2014-2015). These differences arise from the complex interplay of exposure, environment, IAV genetics, and host factors. A crucial host factor that contributes to heterogeneity of IAV infection is sex. For children and older individuals, males are more likely to experience severe disease, while females of child-bearing age have greater severity. As there is strong evidence for 1) the importance of sex in IAV infection, 2) gene expression differences between males and females, and 3) human genetic variation impacting infectious disease in general and specifically IAV infection, synthesis of these three areas may provide crucial mechanistic insight. We hypothesize that sex differences in gene expression are a major driver of heterogeneity in IAV infection. To elucidate these differences, this project will integrate cutting-edge approaches to identify sex-specific differences in transcript abundance and splicing that regulate IAV burden and host response in human cells, IAV challenge volunteers, and natural populations. Further, we will define the genotype x sex interactions that form the mechanistic basis for how genetic diversity contributes to sex differences in IAV infection. To achieve these goals, we have unique datasets of IAV infection heterogeneity in cells from dozens of male and female donors, in nasal curettage and peripheral blood from human IAV challenge subjects, and biobanked samples of natural IAV infection with outcomes ranging from mild infection to death. Computational analyses of these datasets will define 1) sex differences in gene expression that correlate with IAV burden and symptom severity and 2) human SNPs that regulate sex-biased gene expression and flu severity. The transcriptional profiles from these datasets will be used to generate sex-specific biomarkers of IAV infection severity using machine learning approaches. Finally, we will experimentally determine whether the identified sex-biased genes and SNPs regulate IAV burden and host response in cellular models of infection. All results will be available through an easy-to-use web database for exploring this rich dataset as a launchpad for further mechanistic and clinical studies. This project will develop and apply computational methods to generate a high-resolution analysis of how sex and genes interact to impact IAV infection. Understanding the genetic basis for sex differences in IAV infection could lead to new diagnostic approaches in identifying at-risk individuals and novel therapeutic strategies.",,2027,Duke University,549004,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2022 +P22939,5R01AI144798-02,Pandemrix and T Cell Immunology in Narcolepsy,"ABSTRACT: Genetic studies indicate a strong (97%) association of narcolepsy with HLA-DQA1*01:02/DQB1*06:02 (DQ0602), weaker associations with HLA-DP and class I HLA- A*11:01, and effects in other immune related genes such as the TCR αβ loci. The disease is caused by the loss of hypocretin (HCRT)/orexin neurons, as loss of HCRT or HCRT receptors recapitulates symptoms in animal models. Results from our laboratory and from others indicate that a critical step in the disease process is a CD4+ T cell autoimmune response targeting HCRT itself, notably a DQ0602 restricted response to the amidated, C-terminal end of secreted HCRT peptides (HCRTNH2). Indeed, increased T cell response to HCRTNH2 presented by DQ0602 is observed in narcolepsy (our observation), followed by a broader CD4+ T cell responses to other HCRT fragments presented by other HLA class II molecules (other investigators), a result of epitope spreading. This is likely followed by a CD8+ T cell response to HLA class I presented antigens that results in hypocretin cell death and life-long narcolepsy. Unique to narcolepsy, a known environmental factor, the flu, has been associated with initiation of the autoimmune process. Indeed, an increased incidence of narcolepsy in children has been observed following the 2009-2010 pH1N1 Influenza pandemic in China and following vaccination with Pandemrix (GSK), an AS03 adjuvanted pandemic H1N1 2009 (pH1N1) vaccine, but not other vaccines. These observations indicate that epitopes within the pH1N1 virus and vaccine can precipitate narcolepsy in some individuals, findings substantiated by the fact narcolepsy patients have increased T cells binding NP17-31 and pHA273-287, a flu hemagglutinin fragment with significant HCRTNH2 sequence homology. This mechanism is also supported by our preliminary data suggesting TRAJ24 and TRBVB4-2 involvement in pHA273-287, NP17-31 and HCRTNH2 TCR responses, as these TCR segments are modulated by SNPs associated with narcolepsy. In this application, we will further characterize antigenic differences in Pandemrix, Arepanrix and Focetria, vaccines used in the 2009-2010 pH1N1 vaccination campaign, capitalizing on the observation that they have differential risk for precipitating narcolepsy. Our hypothesis, supported by preliminary data, is that Pandemrix contains more pHA273-287 peptide, the main mimic of HCRTNH2 autoimmune responses. In addition, we will continue isolation and characterization of Pandemrix/H1N1 reactive and HCRTNH2 DQ0602 restricted CD4+ T cells. Our hypothesis is that we will ultimately discover pHA273-287/HCRTNH2 and other flu/HCRT cross-reactive cells that use TRAJ24 and TRBVB4-2 segments. Finally, we aim to characterize the phenotype of the corresponding pathogenic cells through single cell sequencing. This high impact study is expected to eventually lead to a) demonstration of molecular mimicry in narcolepsy and b) improved safety of influenza vaccines.",,2025,Stanford University,778420,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P22940,5R01HL146479-03,Immune mechanisms of influenzaÃÃ'¢ÃÂ'Ã'€ÃÂ'Ã'induced exacerbation of atherosclerosis,"Immune mechanisms of Influenza-induced exacerbation of atherosclerosis Influenza A infection is a significant cause of mortality and morbidity worldwide. It is estimated that 3-4 million cases of severe illness and 300,000 deaths due to influenza infection occur annually. During influenza pandemics, the focus is on lung disease, which is the most common cause of death. However, recent epidemiological studies reported significant mortality associated with cardiovascular diseases (CVD) during influenza infection. Atherosclerosis is a common cause of coronary artery disease (CAD), including MI, stroke, and heart failure. The innate and adaptive immune response to modified lipids and vascular endothelial cells causes a series of events that result in plaque formation in medium to large-sized arteries. If inflammatory stimuli continue, plaques become vulnerable to rupture and can cause MI. However, the mechanism involved in the influenza-induced increase in MI incidence is not clear. Our long-term research goal is to understand the impact of lung-vascular interactions in atherosclerosis. The objective of this application is to determine how influenza infection directly or indirectly impacts the outcome of atherosclerosis. In Aim 1, we will characterize myeloid and lymphoid cellular subsets from lung, aorta, and spleen at various time points (early, peak, recovery phase) after fluorescent-labeled (Color-flu) influenza infection to track influenza virus along with the cellular recruitment to the vessel. We will then examine whether antigen presentation is impacted by oxidized LDL (oxLDL) using bone marrow dendritic cells (BMDCs) and T cell re- stimulation in vitro. In Aim 2, we will determine the role of type III IFNs (IFNÃŽÂ>>) systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza-induced exacerbation of atherosclerosis. Further, we will determine the effect of IFNÃŽÂ>> on foam cell formation in macrophages. Finally, we will determine the effect of conditioned media from influenza or type I (IFNβ), type II (IFNγ), and type III (IFNÃŽÂ>>)-treated human bronchial epithelial cells (HBE) on human primary aortic endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. In Aim 3, we will determine the effect of IL-17 neutralization systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza induced-exacerbation of atherosclerosis. Further, we will determine the effect of lung epithelial IL-17RC signaling during influenza infection in atherosclerotic Apoe-/- mice. Finally, we will determine the effect of conditioned media from influenza- infected or IL-17-treated human bronchial epithelial cells (HBE) on vascular endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. At the completion of these studies, we expect to have made mechanistic insights into the cellular trafficking, viral trafficking, systemic and local effects of IFNs and IL-17, and pulmonary epithelial IL-17 signaling in influenza-induced exacerbation of atherosclerosis that may help to identify immune-based therapeutic targets.",,2025,University Of Pittsburgh At Pittsburgh,389555,Other,Not applicable,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2020 +P22942,5R01AI154470-03,Immunobiology of Influenza Virus-related Critical Illness in Young Hosts,"ABSTRACT Influenza virus is a persistent global menace that every year infects an estimated 5-10% of adults and 20-30% of children worldwide causing over 500,000 influenza-related deaths. Most annual influenza infections are in the very young, the elderly, and in individuals with chronic health conditions such as asthma. However, recurrent influenza pandemics caused by the emergence and spread of highly pathogenic novel influenza A strains, such as occurred in 2009, disproportionately causes severe illness in healthy children and younger adults. This study of life-threatening influenza virus lower respiratory tract infection (LRTI) in young hosts is designed by an established multidisciplinary group of investigators to better understand how host innate and adaptive immunity to influenza virus is associated with disease susceptibility, severity and clinical outcomes. In the Pediatric Intensive Care Influenza (PICFLU1) study, we hypothesized that infection with the influenza virus triggers hypercytokinemia and immune dysregulation in a genetically susceptible host resulting in severe life-threatening infection. Confirming our hypothesis, in PICFLU1 (AI084011, enrolling 2008-2016), we identified a hyperinflammatory phenotype coexisting with innate immunosuppression; both were associated with mortality. We also identified associations between functional variants in IFITM3 and MBL2 with pediatric influenza-related death. In the Immunobiology of Influenza Virus-Related Critical Illness in Young Hosts study (PICFLU2, enrolling 2020-2025), we test the hypothesis that distinct severe influenza LRTI phenotypes â€Â"" defined by host immunobiology â€Â"" can be identified for targeted preventive and therapeutic interventions. In this study we aim to: 1. Identify biomarkers in children with severe influenza LRTI that can be used for prognostic stratification and predictive enrichment in future immunomodulatory clinical trials; 2. Determine if pre-existing strain specific immunity to influenza virus protects against life-threatening disease and influences viral shedding and disease severity; and 3. Identify genes essential for anti-viral immunity and/or containment that explain host susceptibility to severe influenza infection or its outcome. To achieve these aims, we will enroll 600 additional children and young adults with confirmed influenza infection (300 intensive care unit and 300 ward or outpatient) across 35 PICFLU sites. Across PICFLU studies (2008-2025) we will have DNA on ~1,000 young hosts infected with influenza virus to identify important endophenotypes for risk stratification and predictive enrichment in future clinical trials targeting prevention of and more rapid recovery from severe influenza-related disease. Identified influenza virus susceptibility and severity genes are potential “druggable targets” for immune modulation. Our findings could personalize the care of young individuals with severe influenza infection based on distinct immunobiologic host phenotypes based on patient age, influenza strain, clinical presentation, innate and adaptive immune biomarkers and host genetics.",,2025,BOSTON CHILDREN'S HOSPITAL,1136468,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Pathogen: natural history, transmission and diagnostics","Prognostic factors for disease severity | Pathogen morphology, shedding & natural history | Immunity",2020 +P22943,4R00AI159136-02,Investigating the development and clonal dynamics of broadly neutralizing B cells against influenza viruses,"PROJECT SUMMARY/ABSTRACT Broadly neutralizing antibodies against the influenza virus surface glycoprotein hemagglutinin (HA) can provide protection from nearly all influenza viruses. However, broadly neutralizing antibodies are rarely induced by vaccination and instead, most antibodies target variable epitopes of the influenza virus HA head domain that only provide narrow protection against a few influenza virus strains. The fundamental mechanisms dictating B cell immunodominance, which B cell specificities are recalled upon virus exposure, remain largely unknown. We identified that first exposure to a novel influenza virus robustly induced antibodies against four broadly neutralizing epitopes of HA. However, repeated exposure to the same virus preferentially drove the recruitment of antibodies targeting variable epitopes of the HA head. Notably, my studies identified that antibodies targeting broadly neutralizing epitopes are enriched for polyreactivity, the ability of a single antibody to bind to multiple molecularly distinct antigens, including foreign and self-antigens. Furthermore, polyreactive naïve B cells targeting broadly neutralizing epitopes are preferentially selected into the memory B cell pool to provide defense against novel pandemic-threat influenza viruses. Based on my preliminary data, I hypothesize that HA epitope specificity influences B cell development, differentiation, and inter-clonal competition, which leads to differences in B cell immunodominance. B cell immunodominance may be dictated by three independent processes: 1) B cells targeting broadly neutralizing epitopes may undergo clonal deletion or become anergic as a result of being polyreactive (Aim 1), 2) B cells targeting broadly neutralizing epitopes differentiate into short-lived B cell subsets as opposed to long-lived B cell subsets (Aim 2), and 3) B cells targeting variable epitopes outcompete B cells targeting broadly neutralizing epitopes (Aim 3). To test these aims, I will use CRISPR/Cas9 to generate B cell receptor knock-in mice expressing the germline version of human monoclonal antibodies targeting four broadly neutralizing epitopes of HA and two variable epitopes of HA. To test Aim 1, I will evaluate B cell development and B cell signaling potential of each B cell receptor knock-in line by generating mixed bone marrow chimeras. In Aim 2, I will determine if epitope specificity shapes B cell differentiation potential by immunizing mice that receive a B cell adoptive transfer from each B cell receptor knock-in line and tracking B cell differentiation and affinity maturation. In Aim 3, I will determine whether B cells targeting a variable epitope outcompete B cells targeting a broadly neutralizing epitope within the germinal center by tracking germinal center responses in HA- immunized mice that have received adoptively transferred B cells targeting each epitope. Knowledge gained from this research will provide critical insight into how broadly neutralizing B cells can be induced, which will aid in the development of a universal influenza virus vaccine that can provide broad protection against all influenza viruses. The additional training afforded by this mentored award will enable me to expand my scientific and professional skillsets, leading to my research independence and successful transition into a faculty position.",,2023,University Of Colorado Denver,248999,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P22944,5U01AI150747-03,DYNAMICS AND EVOLUTION OF IMMUNE RESPONSES TO INFLUENZA VIRUSES,"PROJECT SUMMARY/ABSTRACT Our goal is to develop a quantitative framework for the generation, boosting and maintenance of immunological memory. Mathematical models are useful because immunization and infection involve the interaction of rapidly changing populations of virus and multiple populations of immune cells. We first develop and validate models using experiments in mice. We then use these validated models to analyze data from human vaccination studies. Aim 1 asks how prior immunity affects and potentially limit the boosting of immunity and apply this to influenza. Our approach is to develop models to understand why prior immunity limits boosting of antibodies to conserved regions of the virus. Specifically, we use our models to better understand how prior immunity might limit boosting of antibody responses to conserved regions on the stem of the hemagglutinin molecule that is the focus of universal influenza vaccines. Aim 2 considers the factors that affect the durability of humoral immune memory, and address questions such as why memory generated by immunization with protein antigens is less durable than immunity generated by virus infection, and how prior immunity can differentially affect the boosting and generation of memory to new strains of influenza. Aim 3 considers the generation of CD8 T cell memory to influenza and yellow fever. We will determine how repeated exposure to influenza affects the diversity of the CD8 T cell responses generated. We have access to a unique dataset that follows the number of YFV-specific CD8 T cells, changes in their phenotype, and their turnover from heavy water labelling studies for a period of over one year. Our analysis of this dataset will allow us to address an ongoing controversy regarding whether are long-term memory CD8 memory stem cells are generated rapidly after immunization or only gradually over time. Aim 4 describes computational tools that we will build for B cell receptor sequence analysis and visualization, and for simulation of the dynamics of immune responses. These tools will be widely accessible online, and promoted at workshops and scientific symposia we organize.",,2025,EMORY UNIVERSITY,1176222,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +P22945,5R21AI160779-02,Dissecting ADP-ribosylation as an innate immune response countering influenza virus replication,"ABSTRACT Viral infections manipulate diverse post-translational modifications (PTMs), altering existing protein landscapes to create cellular environments favorable to replication. PTMs allow for rapid modulation of host environments by altering protein abundance, localization, and activity. Because of their dynamic nature, PTMs typify ideal immune response effectors or initiators. Our data identifies ADP-ribosylation, the modification of proteins with ADP-ribose (ADPr), as a rapid, immune-like response from infected cells that constitutes an antiviral response that counters influenza virus infection. Using cutting-edge ADPr-specific mass spectrometry approaches, we have characterized with single amino acid resolution the ADP-ribosylome during influenza virus infection and identified thousands of modifications on viral and host proteins. ADP-ribosylation has been associated with antiviral responses against multiple viruses. However, little is known about how viral infections trigger this response or the activiral mechanism(s) of ADP-ribosylation and poly(ADPr)-polymerases (PARPs), the enzymes that catalyze addition of ADPr to proteins. Here, we propose studies of ADP-ribosylation during influenza virus infection. We will identify the functional consequences of specific ADPr modifications, and building on our unique ADP-ribosylome dataset, investigate how ADP-ribosylation alters the function of specific viral and host proteins. We will interrogate the cellular pathways responsible for initiating ADP-ribosylation responses, defining the molecular triggers and PARPs that are activated during influenza virus infection. These experiments will elucidate the mechanisms of ADPr-mediated viral inhibition, the factors that trigger this response, and how viruses counter it, establishing ADP-ribosylation as a key aspect of cellular antiviral responses and perhaps as an entirely independent arm of antiviral defenses.",,2024,UNIVERSITY OF WISCONSIN-MADISON,195030,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22948,1R01HL164821-01,Alveolar responses to viral lung infection,"PROJECT SUMMARY / ABSTRACT Significance. One-third of patients with severe lung infection by influenza A virus (IAV) develop secondary infection by inhaled Staphylococcus aureus (SA). Coinfection by IAV and SA causes about 30% mortality despite therapy. It remains unclear how IAV promotes secondary SA infection, particularly in lung alveoli. This issue is important because alveoli are the anatomical site of fatal SA-induced Acute Lung Injury (ALI), but alveolar defense mechanisms, including alveolar wall liquid (AWL) secretion, should prevent SA stabilization and coinfection initiation. The long-term objective of this proposal is to determine alveolar responses to IAV that promote secondary SA infection in alveoli, resulting in SA-induced alveolar damage, ALI, and mortality. The hypothesis is IAV lung infection inhibits AWL secretion, a homeostatic mechanism by which alveoli clear inhaled particles. The inhibition causes alveolar retention of SA and the secreted SA toxin, alpha hemolysin (Hla). The retention enhances alveolar contact with SA and Hla, promoting SA stabilization against the alveolar wall and Hla-induced alveolar fluid barrier loss, leading to alveolar edema and fatal ALI. In addition to directly supporting the hypothesis, preliminary data indicate IAV lung infection caused: (A) dephosphorylation, hence inactivation of the alveolar cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, the critical protein for AWL secretion; and (B) methylation of the CFTR-dephosphorylating protein, protein phosphatase 2A (PP2A) catalytic subunit (PP2Ac), which may promote PP2Ac-CFTR interactions. Specific Aims are as follows. Aim 1 will define the role of CFTR in alveolar retention of inhaled SA. Aim 2 will define the role of PP2Ac methylation in IAV-induced inhibition of AWL secretion. Since our preliminary data suggest CFTR and the PP2Ac- methylating enzyme, leucine carboxyl methyltransferase 1 (LCMT1) may represent new therapeutic targets to restore AWL secretion in IAV-infected lungs, Aim 3 will test the therapeutic potential of CFTR- and LCMT1- targeted approaches to protect against coinfection-induced alveolar damage, ALI, and mortality. These Aims will be achieved using our established methods, which include cell culture, mouse models of ALI, and real-time confocal microscopy of live, intact mouse and human lungs. Determinations in IAV-infected mice will include measures of: (1) alveolar retention of SA; (2) AWL secretion; (3) alveolar CFTR phosphorylation status; (4) alveolar PP2Ac methylation status; (5) SA- and Hla- alveolar epithelial damage and alveolar barrier loss; and (6) SA-induced pulmonary edema and mortality. We will use: (i) wild type mice treated with inhibitors of alveolar PP2Ac-CFTR and PP2Ac-LCMT1 interactions, including drug inhibitors, plasmid DNA encoding mutant proteins, and siRNA; and (ii) transgenic mice lacking alveolar epithelial CFTR and LCMT1 expression. This proposal is expected to achieve new insights into the molecular mechanisms by which IAV disrupts critical alveolar function leading to fatal ALI, and to establish restoration of AWL secretion â€Â"" that is, “AWL rescue” â€Â"" as a new therapeutic approach for ALI caused by IAV-SA coinfection. Therefore, this proposal addresses the NHLBI mission.",,2027,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,553834,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Pre-clinical studies",2022 +P22950,5U01IP001136-02,Modeling toolkit to evaluate multifaceted control strategies for seasonal and pandemic influenza,"PROJECT SUMMARY We will develop a data-driven model of seasonal and pandemic influenza transmission throughout the US to accelerate robust assessments of multifaceted influenza intervention strategies. We will work closely with the CDC Modeling Network to advance the fidelity, transparency and translation of models as an evidence base for influenza policy making, prevention and control. This project extends a metapopulation model of influenza transmission within and between 217 major metropolitan areas in the US that we are developing in collaboration with the CDC Modeling Network. The model includes travel between cities, age- and risk-group specific susceptibility, probability of clinical outcomes, intervention efficacies and uptake rates, as well as the impacts of local climate and school calendars on transmission rates. Using a range of public health, epidemiological, societal and economic metrics, the model can flexibly evaluate thousands of candidate intervention strategies, including time- and location-based combinations of vaccines, antivirals, and social distancing measures with potential subgroup-specific prioritization. Our proposal includes four major aims. In Aim 1, we will extend our US Influenza Model to include the co- circulation of multiple viruses competing via transient heterosubtypic immunity. We will derive new estimates for the duration and magnitude of heterosubtypic immunity and design strain-specific strategies for effectively controlling co-circulating seasonal and pandemic influenza viruses. In Aim 2, we will evaluate intervention strategies that leverage newly approved and combined antiviral drugs. We will fit within-host viral dynamic models to clinical data on new antivirals to estimate the efficacy of various drug regimens in different subpopulations with respect to disease severity, infectiousness, and the risk of antiviral resistance. In Aim 3, we will build a granular within-city model of influenza transmission based on abundant data and local collaborations with public health and healthcare leaders in the Austin-Round Rock Metropolitan Area. We will apply the model to elucidate socioeconomic and geographic disparities in influenza risk and design interventions that ameliorate such gaps. In Aim 4, we will build an interactive visualization platform that allows users to specify epidemic scenarios, implement layered interventions as simulations unfold, and view the model dynamics through the lens of a surveillance module based on the CDC’s FluView Interactive portal. We will work extensively with the CDC Modeling Network to build a diverse portfolio of validated models and best practices for collaborative decision support. Our projects will contribute flexible models for the evaluation of multifaceted influenza interventions, elucidate competition among influenza viruses and the efficacies of novel antivirals, and provide insights into socioeconomic disparities in influenza burden. Furthermore, our innovative visualization tool will broadly support the translation of science to public policy.",,2025,University Of Texas At Austin,737051,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Research to inform ethical issues,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Research to inform ethical issues related to Public Health Measures,2020 +P22951,1R21AI153882-01A1,Mathematical Modeling of Influenza Severity in Outbred Mice,"PROJECT SUMMARY In the United States, pulmonary influenza infection occurs annually in 5-20% of the population with mortality in the range of 30,000 deaths. The recent 2009 influenza H1N1 pandemic illustrated the potential for higher infection rates, which were reported to be as high as 45% in certain age groups. The 2017-18 influenza season had the highest pediatric mortalities since the 2009 pandemic. Influenza infection is known to result in a broad spectrum of disease phenotypes in humans, although severe pneumonia is relatively rare. Despite this, severe disease often requires advanced supportive care in the young, including previously healthy children. Host factors involved in determining the outcome of influenza infection are unclear and children are known to be at higher risk of severe disease. First life exposure to influenza is also thought to dictate life-long immunity. Little is known about the effects of young age and gender on influenza responses and severity. This underscores the importance of understanding influenza pathogenesis in a pediatric population. Influenza pathogenesis is likely mediated in large part by exuberant inflammatory host responses in the lung. It is likely that predictive soluble inflammatory mediators are present in severe infection. Further, predictive biomarkers or mathematical models of influenza pneumonia severity would enhance clinical decision making and patient care. We propose that machine learning and mathematical modeling of host immune endpoints will define a molecular fingerprint of severe influenza pneumonia in juveniles. This hypothesis will be tested in two Aims. Aim 1 will focus on characteristic molecular pathways related to influenza severity in juvenile animals, using outbred mice. We will utilize machine learning and new mathematical approaches for pathway and biomarker selection. Aim 2 will test mathematical models of influenza pathogenesis to elucidate new mechanisms that drive lung injury. The overall goal of the proposed study is to identify novel biomarkers and mechanistic models of influenza pneumonia severity that can be applied to children. To accomplish this we will use a broad, exploratory, and unbiased approach. Candidate biomarkers and pathways would then be evaluated in future mechanistic and translational studies in mice and humans.",,2022,University Of Pittsburgh At Pittsburgh,228212,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Prognostic factors for disease severity",2020 +P22952,5U01IP001141-02,Individual-based Simulation of Seasonal and Pandemic Influenza Epidemics - supplement Emergency Response to the COVID-19 Pandemic,"Project Abstract Seasonal influenza caused an estimated 48.8 million illnesses, 22.7 million health care visits, 959,000 hospitalizations, and 79,400 deaths in 2017-18. Influenza is a particularly complicated disease to prevent as the influenza virus itself changes over time, and unlike vaccinations for measles or hepatitis B, the effectiveness of annual vaccination may be limited if the particular strain that appears in an outbreak is not represented in the vaccine. In addition, the immunity produced by vaccination declines over time, and many individuals, especially the elderly, may lose protection toward the end of an influenza season. The goals of iMPH: Influenza Modeling for Public Health are to bring together four experienced modeling groups including the Public Health Dynamics Laboratory (PHDL) that has significant experience as a MIDAS Center of Excellence in the agent-based modeling of influenza, the Pittsburgh Vaccine Research Group (PittVax), vaccine policy experts who are site leads in both the inpatient and outpatient CDC influenza vaccine effectiveness (VE) networks, the DELPHI (Developing the Theory and Practice of Epidemiological Forecasting) group at CMU, the most accurate US influenza prediction group, and the current MIDAS Network Coordination Center (MCC) that brings major data and model coordination expertise. Our specific Aims are to create realistic, biologically based models of influenza, including the development and maintenance of immunity over time through either the development of the disease or vaccination so that we can test the benefit of different prevention strategies in seasonal or pandemic influenza. Specifically, we will examine strategies such as: enhanced vaccines that create high initial antibody levels, the addition of a second, mid-season vaccine, or potentially delaying vaccination in some individuals until later in the season. We will also examine the effectiveness of vaccination policies over a multi-year time, such as different vaccinations for individuals who have had previous influenza, and consideration of every-other year vaccines, Finally we will examine community-level interventions, such as school closures and working from home to impact the spread of influenza over a season. As a CDC Influenza Modeling Center, we will also collaborate with other centers to develop rapid responses to current influenza threats, to share data, models and results to provide higher confidence to the CDC that model-based recommendations can be used to formulate local, state and national influenza policy.",,2025,University Of Pittsburgh At Pittsburgh,750000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control | Policies for public health, disease control & community resilience",Immunity | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P22953,3UM1AI148576-02S6,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2022,Emory University,2044564,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P22954,1R13AI164787-01,21st Annual Rocky Mountain Virology Association Conference,"Conference Summary The Rocky Mountain Virology Association will hold its 21st annual meeting in October 2021. The meeting brings together regional and national investigators in virology and prion biology for a 3-day retreat-style conference with extensive interaction and collaboration. The original meeting was organized by investigators in Colorado and Wyoming who were interested in the free and open exchange of scientific data and ideas concerning general virology in a venue that promotes collaboration among students, post-doctoral researchers and faculty members. Specifically, our annual meeting at the Mountain Campus of Colorado State University encourages young scientists to present their research and receive feedback from established scientists. The goals are promotion of scientific interactions and training. A major benefit of participation has been the novel collaborations that arise between scientists in different disciplines. The topics discussed include medical virology (vaccines, epidemiology, viral zoonoses), arthropod-borne diseases (RNA viruses, metabolism, viral vectors and vector biology), host defenses (viral immunology and pathogenesis), prion biology, cancer biology and systems biology. Special sessions on HIV pathogenesis, vaccine development, pandemic influenza, prions, virus discovery and the global impact of viral diseases have been featured at past meetings. The 2020 meeting featured perhaps the most disparate, yet now intimately tied fields, epidemiology and epigenetics. The next meeting will feature a retrospective on the COVID-19 pandemic with discussions on successful approaches and establishment of systems for future challenges. The attendees include scientists from Colorado State University, The University of Colorado, the University of Wyoming, the University of Northern Colorado, the Centers for Disease Control (Fort Collins) and the Department of Agriculture Animal and Plant Health Inspection Service as well as scientists from regional biotech companies, and universities in Iowa, Idaho, Nebraska, Kansas, Montana, New Mexico and Utah. The Rocky Mountain Virology Association was incorporated in 2010 as a tax-exempt educational charity (Section 501(c)(3)). Our board of directors is charged with encouraging student and junior faculty involvement by minimizing costs as we encourage women and minorities to participate in all stages of program presentation and development. Everyone involved in programming is a volunteer. Our attendance is limited by the venue to a maximum of 110 individuals. The growth of the meeting to capacity illustrates a strong desire on the part of regional scientists to participate. Funds for this proposal are requested to provide minority grants and childcare, reduced registration fees for graduate students, post-doctoral fellows and early-stage investigators, and for travel and housing for seven invited speakers. Registration fees, charitable contributions, and sponsorships cover the base costs for the meeting. The RMVA has been a source of communication and collaboration for the Rocky Mountain region, with outreach across the nation, for twenty years. Our efforts and NIAID support have expanded interest in this meeting to national and international levels to the benefit of all.",,2022,Colorado State University,15000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P22955,5U01IP001137-02,FluMod - Center for the Multiscale Modeling of Pandemic and seasonal Flu Prevention and Control,"PROJECT SUMMARY In this proposal we plan to contribute addressing the above foundational and operational challenges by advancing the science of influenza modeling and contributing novel methods and data sources that will increase the accuracy and availability of seasonal and pandemic influenza models. To address these challenges, we plan to build on the unique mechanistic spatially structured modeling approaches developed by our consortium, that includes stochastic metapopulation models and fully developed agent-based models nested together in our global epidemic and mobility modeling (GLEAM) approach. The objective of this project is to generate novel and actionable scientific insights from dynamic transmission models of influenza transmission that effectively integrate key socio-demographic indicators of the focus population, as well as a wide spectrum of pharmaceutical and non-pharmaceutical interventions. Our proposed work in specific aim 1 (A1) will leverage our global modeling (from the global to local scale) framework that can be used to explore the multi-year impact of influenza vaccination, antiviral prophylaxis/treatment, and community mitigation during influenza seasons and pandemics. Our specific aim 2 (A2) will focus on using high quality data to model heterogeneous transmission drivers and novel contact pattern stratifications that will allow us to guide mitigation strategies and prioritization for interventions. In our Aim 3 (A3) we will use artificial intelligence approaches to identify interventions that are particularly synergistic and well-suited to particular epidemic scenarios, for seasonal and pandemic influenza. Our overarching goal is to provide a modeling portfolio with flexible and innovative mathematical and computational approaches. We aim to address several questions commonly asked about seasonal and pandemic influenza and match these with analytical methods and outbreak projections. The modeling and data developed in this project can help facilitate and justify transparent public health decisions, while contributing to the definition of standard methods for model selection and validation. Finally, our influenza modeling platform can also benefit the broader network of modeling teams and can be used to improve result sharing and harmonization of modeling approaches.",,2025,Northeastern University,750000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P22956,5R01AI154894-02,Role of spatial structure in shaping viral population diversity and evolution,"Summary Viral evolution enables the emergence of novel viral pathogens in the human population. The evolution of influenza A virus is also critical for the maintenance of seasonal lineages in the context of host immunity. Evolution can result from selection, leading to increased fitness, or stochastic processes that typically decrease fitness. The relative potency of selective and stochastic forces is therefore a critical determinant of the adaptive potential of a population. Based on evolutionary theory, we hypothesize that the magnitude of stochastic effects in viral evolution is strongly impacted by the spatial structure that characterizes viral spread within a host. In other words, the expansion of a virus population in space may give rise to random, within-host bottlenecks and founder effects that weaken the efficiency of natural selection. Factors that shape viral spread - including viral phenotypes, host responses and physical characteristics of the host environment - are therefore predicted to impact viral genetic diversity and evolution. Our overarching hypothesis is that viral features that modulate viral spatial structure also modulate viral diversity and evolution. We will test this hypothesis for influenza A virus using a well-integrated combination of simulation modeling and experimental approaches. In Aim 1, we will use computational, cell culture and ferret models to examine the consequences of spatially structured spread for genetic diversity of viral populations. For our experiments, we will use viruses carrying a selectively neutral barcode to allow robust quantification of viral diversity. In this way, the degree to which stochastic effects dominate viral dynamics will be examined under a range of conditions. In Aim 2, we will evaluate the consequences of spatially structured spread for both purifying and positive selection. Computational approaches will be used to develop hypotheses of how long distance virus dispersal impacts the ability of de novo beneficial and deleterious mutations to reach dominance. These model predictions will then be tested using experimental evolution under conditions of common vs. rare long distance dispersal. In this way, we will test the theoretical concept that stochastic effects associated with spatial structure impede the ability of natural selection to act on expanding populations. Taken together, the research proposed in these two aims will uncover the importance of spatial structure to viral population biology and evolution, deepening our fundamental understanding of the forces shaping viral evolution in nature.",,2025,Emory University,559622,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P22957,1R01AI150885-01A1,High-throughput assays and small-molecule discovery of antiviral candidates targeting influenza hemagglutinin,"PROJECT SUMMARY / ABSTRACT Influenza A viruses exhibit extreme diversity as exemplified by the multiple serotypes of the hemagglutinin (HA, H1-H18) and neuraminidase (NA, N1-N11) surface antigens. To date, only 3 of 198 possible combinations of HA and NA in avian and other animal reservoirs have been associated with human pandemics (H1N1, H2N2, H3N2). Recent appearances of H5N1, H6N1, H7N7, H7N9, H9N2, and H10N8 in humans are constant reminders of the potential for devastating new pandemics. Influenza B viruses with its two lineages further increase the health and economic burdens of seasonal influenza. No effective antiviral drugs are currently available for preventing entry of influenza A or B viruses into host cells (scientific premise). However, relatively recent discoveries of broadly neutralizing antibodies to human influenza viruses and concomitant structural studies have identified sites-of-vulnerability on the HA in pandemic, seasonal, and emerging influenza viruses. These HA surface sites include the receptor binding site and membrane-proximal stem housing the fusion machinery, both of which are essential for cellular infection. Common features for recognition of these sites can now be exploited in design of small molecules to ultimately develop broadly applicable influenza antivirals. Here, we will employ this structural information into the optimization and execution of high-throughput assays to identify new small-molecule scaffolds that target the highly conserved and vulnerable stem-binding site. High- throughput screening will be performed in parallel on representative HAs from influenza A group 1 against 600K structurally diverse molecules (SA1). We will also subject group 2 and influenza B HAs to a 300K compound screen (SA2). Validated hit compounds will be prioritized based on affinity and breadth across HAs and top candidates will be rigorously optimized into lead molecules by x-ray structure-based design cycled with medicinal chemistry. Biophysical binding, cellular infectivity and resistance assays (e.g., combinatorial viral libraries of HA mutants) will aid in iterative design, selection, and characterization of potential novel therapeutic candidates with favorable drug-like properties. All of these methods are actively employed in the Wolan and Wilson laboratories. As proof-of-concept for this approach, we identified a molecule with modest affinity to the stem of group 1 HAs with an HT assay of our own design. Its co-crystal structure with HA provided critical information towards design and synthesis of a focused compound library, which we used to produce a stereoselective molecule with nanomolar affinity and antiviral activity. Our overall goal is to identify and improve molecules with broad potency against the stem of groups 1 and 2 as well as flu B HAs. To our knowledge, we are the first to design an assay against group 2 and flu B HAs amenable to HTS (innovation). We anticipate that several classes of stem-targeted compound scaffolds will be identified with nanomolar affinity to HAs with cellular antiviral activity and suitable PK-ADME properties. Future efforts will include animal models of influenza infections to further validate our antivirals with the ultimate goal of combatting future influenza pandemics and seasonal epidemics.",,2025,"SCRIPPS RESEARCH INSTITUTE, THE",678526,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H2 | H3 | H5 | H6 | H7 | H10 | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22958,5R01AI147109-02,Rapid Manufacturing of a Universal Flu Vaccine Using TMV-conjugated Centralized Antigens,"Project Abstract This interdisciplinary proposal brings together three highly successful but independent technologies to create an effective and broadly neutralizing universal influenza vaccine. Our approach combines breath of immunity, by using a consensus HA strategy, production speed and capacity by working with Kentucky BioProcessing (KBP), who can express HA protein in plants, and vastly improved subunit vaccine potency using a TMV-HA conjugation approach to create a candidate universal influenza virus vaccine. Based on our preclinical data on three influenza A strains, we expect our approach will drive long term immunity that is balanced between antibody and cellular immunity, providing potential for overlapping mechanisms of immune protection. We bring together a strong team of different disciplines with a combined goal to quickly show proof of concept with H1, H3, H5, and M2e antigens. Our Specific Aims are as follows: 1) Production of TMV-HA conjugates of centralized H1, H3, H5 genes and M2e peptide, 2) Immune response analysis, murine challenge studies and 3) Translational and ferret studies of TMV-HAc and TMV-M2e vaccines. Dr. Weaver has developed a computational method to express an ancestral sequence of HA, representing a consensus of sequences within an Influenza subtype. These vaccines protect against drifted seasonal influenza variants better than a traditional trivalent inactivated virus vaccine. In partnership with KBP, we will use established plant expression methods to produce centralized HA proteins, with the capacity to produce protein for the planned studies and for future clinical trial development. HA consensus protein will be fused to the surface of Tobacco Mosaic virus (TMV) by chemical conjugation, a method developed by Dr. McCormick to improve HA subunit vaccine potency. TMV-HA vaccines will also be combined with a highly conserved M2e peptide vaccine, to broaden protection and reduce vaccine dose. Immunological analysis will be used to confirm vaccine potency, in order to optimize dose, schedule and route of administration. Vaccine efficacy and broadly protective immunity will be confirmed by lethal influenza challenge using 9 divergent virus types in a murine model of disease. Finally, vaccine formulations will be re-tested in ferrets, a models of influenza infection which more closely mimics the progress of disease in humans. Our vaccine is designed to drive local and systemic immunity after either intranasal or intramuscular routes of administration, and we will use immunogenicity and pathogen challenge data to define an optimized single dose vaccine formulation. Our goal is to generate an effective universal vaccine against influenza that can be manufactured at scale, with significant potential for translation into a universal vaccine product that is ready for clinical testing.",,2025,UNIVERSITY OF NEBRASKA LINCOLN,633642,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3 | H5 | Other,Unspecified,,Unspecified,Unspecified,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22959,5R21AI152006-02,Assessing Flu-specific Humoral Immunity in Human Lung after Ex Vivo Lung Perfusion,"PROJECT SUMMARY. Broadly reactive humoral immune responses to flu protect against viral variants. Murine data shows that the flu-specific memory B cells (Bmem) in the lung are cross-protective across a number of influenza strains and are functionally distinct from circulating and lymphoid counterparts. As yet we do not know if flu-specific Bmem in the human lung are cross-protective and bridging this knowledge gap is important to design the appropriate vaccine regimens that are universally protective against flu. Flu-specific Bmem in ex vivo lung tissues are rare and this represents a significant technical hurdle in assaying the flu-specific Bmem response in human lung tissues. In order to address this technical hurdle, this application seeks to establish a model system wherein human lung tissue is challenged with influenza virus and maintained viable after this challenge on an advanced cardiopulmonary modality called Ex Vivo Lung Perfusion or EVLP. We anticipate this model will allow us to enumerate and analyze the flu-specific Bmem response at scale in ex vivo human lung tissues. We also anticipate that this model system will allow us to compare binding reactivity to viral variants between flu- specific Bmem located in lung versus mediastinal lymph node tissues to define where cross-protective immunity exists in the respiratory tract.",,2023,University Of Alabama At Birmingham,222750,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity | Disease models",2020 +P22960,3UM1AI148452-02S1,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2021,Vanderbilt University Medical Center,192338,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P22961,3UM1AI148452-02S2,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2023,Vanderbilt University Medical Center,4613138,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P22962,1R41AI162408-01,Small molecule inhibitors of influenza virus nucleoprotein,"Influenza is a continuing worldwide public health threat, with seasonal activity that is not adequately controlled by the yearly vaccine program. The severity of this problem is likely to increase with emergence of new influenza virus strains in the human population, and this situation is made even more complex by the COVID-19 pandemic. Both COVID-19 and the 2009 H1N1 influenza pandemics are reminders of the challenge posed by emergent viruses, and they also highlight weaknesses in global preparedness should additional threats arise. Despite existing seasonal vaccines and two classes of chemical pharmaceuticals in current use, there is an urgent need for new anti-influenza therapeutic agents to provide broader coverage, ensure against emergence of drug resistance and prepare for future inevitable pandemics. This Phase I STTR application is to develop potent inhibitors to a novel viral target, the nucleoprotein NP. We have identified and characterized two inhibitor classes, with promising affinity and potency, lack of cytotoxicity and good PK properties. The goals of Phase I are to demonstrate in vivo efficacy in the mouse model, select and characterize escape mutants in cell culture, and further explore one of our series with excellent opportunities for additional medicinal chemistry. Included in this effort is the important goal of creating broad-spectrum antivirals that are active against H1N1 and H3N2 seasonal strains â€Â"" which is achievable given the highly conserved nature of the NP target. Our approach is divided among three, integrated Specific Aims. In Aim 1 the BALB/c mouse infection model will be used for efficacy studies of leads JJNP9-4 and MC-2, based on successful MTD and PK studies in the mouse. Several parameters will be measured as indicators of efficacy, including mortality, body weight, viral load in the lung and other standard behavioral and physical parameters. In Aim 2, JJNP9-4 and MC-2 will be used for selection of virus escape mutants, followed by sequencing of the mutants, reverse genetic construction of drug-resistant variants, and characterization of viral fitness of the escape mutants. The results will inform future structural studies to identify the binding sites of the inhibitors. In Aim 3 the potency of one inhibitor series will be addressed by developing an SAR with the synthesis of individual analogs and combinatorial libraries Two top-prioritized analogs will be used for MTD, PK and efficacy studies in the mouse model of infection.",,2024,"ALEXANDER BIODISCOVERIES, LLC",300000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3,H1N1,,H3N2,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +P22963,5R21AI149648-02,Determine the minimal level of replication required for broad protective immunity of influenza vaccine,"Project Summary Influenza A virus causes disease in 5%-20% of the population with over 200,000 hospitalizations annually in US. The antigen drift and shift of influenza virus due to rapid evolution pose a serious challenge for annual flu vaccination program, which is effective depending on the accurate prediction of the influenza serotypes that will be circulating in the next flu season. The recent failure of influenza vaccine and potential outbreak of influenza pandemics highlights the urgent need for a vaccine that can provide broad protection. Interferon (IFN) is a critical component of the innate immune system and also the bridge between the innate and adaptive immune responses. We recently studied the anti-IFN function of influenza genome using a quantitative and high-throughput genomics system. By incorporating eight IFN-sensitive mutations into influenza genome, we generated a Hyper Interferon Sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in wild type and immune-deficient SCID mice, but fully competent in IFNAR-deficient mice. HIS provides protection against homologous and heterologous viral challenges. Our central hypothesis is that systematical elimination of IFN-evasion functions on multiple segments of the virus genome generates proper induction of innate immune response, which is essential for establishing long term memory B cell response and T cell response by live attenuated influenza vaccine. Our objective is to determine the minimal replication capacity required for live attenuated influenza virus vaccine, identify and generate single-round infection HIS virus, which can induce strong IFNR signaling in vitro, but has no replication capacity in vivo due to innate immune response. Such vaccine virus candidate would have confined one-round infection during immunization whereas the IFN inducing activity would be strong enough to illicit broad protective immunity. We will generate hyper IFN sensitive virus that has no replication capacity in vivo, and characterize its replication kinetics and responsiveness to IFN in lung epithelial cells. After we obtain such virus, we will infect mice with vaccine candidate viruses and characterize the induced immune responses. Finally, we will determine protection efficacy of vaccine candidate viruses against different strains of influenza virus in vivo. The results achieved from this project will advance our understanding of influenza vaccine development and facilitate the development of universal influenza vaccine.",,2021,University Of California Los Angeles,234000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +P22964,5R01AI146588-02,Biomimetic nanoparticles to enhance the breadth of influenza vaccines,"Abstract Current influenza (flu) vaccines are effective only for closely matched flu viral strains and must be updated annually to address constant antigenic shift/drifts of surface hemagglutinin (HA) and/or neuraminidase (NA) of the virus. Even with annual update, there have been years in which flu vaccines were ineffective due to significant differences in antigenicity of HA and/or NA between the strains used for preparing the vaccines and the circulating ones, leaving us at high risk of pandemics in case a new and highly pathological virus emerges. It is without any doubt that a “Universal” flu vaccine that can protect against both seasonal (matched or mismatched) and pandemic flu viruses is urgently needed, but it remains “an alchemist’s dream” so far. We developed a novel adjuvant by encapsulation of cGAMP, an agonist of the stimulator of interferon (IFN) gene (STING), into pulmonary surfactant (PS)-biomimetic liposomes (PS-GMNP). The adjuvant, alongside an inactivated flu vaccine, robustly stimulated humoral and CD8+ T cell immune responses that resemble those ocurring during the early phase of viral infection both in magnitude and in dynamics. Strikingly, a single dose of PS-GMNP-adjuvant flu vaccine elicited strong cross-protection against a lethal challenge of diverse heterosubtypic flu A viruses as early as 2 days after immunization. While stimulating robust heterosubtypic immunity, the adjuvant did not cause any adverse events in lung histology, body weight or temperature, in sharp contrast to the severe lung inflammation and death caused by flu viral infection. In this proposal, we will investigate the cellular and humoral immune responses essential to the cross-protection induced by PS- GMNP-adjuvanted flu vaccines. Specifically, we will determine whether PS-GMNP can expand cross-reactive CD8+ T cells and induce broadly neutralizing antibodies (bnAbs), pivotal to PS-GMNP-induced cross- protection. In Aim 2, we will preclude any adverse effects of pre-existing immunity on the adjuvanticity of PS- GMNP and extend the cross-protection to pre-pandemic wild type H5N1 and H7N9 viruses to establish its clinical potentials. Distinguished from conventional adjuvants that activate primarily antigen-presenting cells (APCs), cGAMP delivered by PS-GMNP activated both alveolar macrophages (aMɸ) and alveolar epithelial cells (AEC), which can be crucial since similar activation of these two types of cells is also observed during flu viral infection. Two alternative approaches will be employed in Aim 3 to corroborate indispensable function of AEC and/or aMɸ in PS-GMNP-mediated heterosubtypic immunity, including a blockade of cell-gap junctions and generation of chimeric mice of wild type and STING-deficient bone marrow (BM) cells. The study, if successful, could provide invaluable information about clinical potentials for PS-GMNP to widen the breadth of existing flu vaccines toward a “Universe” one, which will have a huge and immediate impact on global health.",,2025,MASSACHUSETTS GENERAL HOSPITAL,500250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | H7,,,,H5N1,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +P22966,5U01EB029085-04,A Microphysiological Mimicry of Human Lung-Bone Marrow Organ-Organ Crosstalk On-a-Chip,"PROJECT SUMMARY. Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 20 years. Influenza A viruses (IAVs) comprise 50% of the emerging respiratory viruses and can cause substantial morbidity and mortality. IAVs can infect a diversity of avian and mammalian species, including humans, and have the remarkable capacity to evolve and adapt to new hosts. Despite the tremendous progress made in virology and epidemiology, which subtype or strain of IAV will cause the next outbreak remains unpredictable. Importantly, there is no clinically simulating, pathophysiologically relevant, and readily available in vitro multi-organ system for predicting the pathogenicity of emerging and re-emerging influenza viruses in humans. Recent compelling evidence have revealed opposing roles for two major classes of bone marrow (BM)-produced innate immune cells in shaping the outcome of IAV infection, with neutrophils offering protection and increase in circulating monocytes being associated with increased pathology. Thus, selective mobilization of either of these two distinct cell types in response to pulmonary infection with IAV can indirectly reveal potential pathogenicity of a given viral strain. The overarching goal of this project is to develop a highly innovative, reductionist, yet advanced and complex, physiologically relevant in vitro model of influenza infection in humans utilizing Organ-on-Chip technology in order to predict virulence and infectivity of different IAV strains, by reproducing clinically and in vivo-observed immunological correlates of infection severity. More specifically, we will engineer a first-in-kind fluidically integrated multi- organ system that recreates BM-lung axis, using primary human-derived cells, for real-time analysis of inflammation and leukocyte mobilization in response to influenza challenge. Our central hypothesis is that this dynamic living microsystem can recapitulate differential immune cell mobilization and tissue pathology in response to high-pathogenicity vs. low-pathogenicity IAV infections in vitro. To address the hypothesis, we propose the following specific aims: (1) to engineer a living and hematopoietically active human BM-on-a-Chip and microfluidically link it to a human Lung Small Airway-on-a-Chip that our team has previously developed and characterize homeostatic physiology and organ-organ crosstalk; and (3) to challenge the BM-Lung microsystem with airborne IAVs under rhythmic breathing and reproduce differential leukocyte mobilization and tissue damage in response to distinctly pathogenic viral strains. Such a novel platform holds great potential in emulating and predicting pathogenicity of IAVs (e.g., during outbreaks, pandemics or when presence of a highly virulent strain is speculated), utilizing human cells isolated from desired donor/patient populations, and without needing to adapt the virus for host (as required for some animal studies). In addition, it can considerably accelerate drug development studies by enabling personalized drug efficacy testing and identification of new therapeutic targets.",,2024,University Of Pittsburgh At Pittsburgh,389613,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2021 +P22967,1R21AI153812-01A1,Human Genetic Variation Regulating Transcriptional Response and Cellular Susceptibility to Influenza,"Project Summary/Abstract It is estimated that 50-100 million people (~5% of the global population) died from the 1918 influenza pandemic. While influenza infections usually do not cause such severe disease, ~30 million are infected every year in the United States alone (2014-2015). However, there are broad differences in influenza susceptibility and severity, with outcomes from asymptomatic infections (~16%) to death (0.2% in 2014-2015). These differences arise from the complex interplay of exposure, environment, influenza genetics, and human genetics. The overall goal of my lab is to understand how human genetic diversity regulates susceptibility and severity of infections. Famous examples of genetic differences that profoundly impact susceptibility include sickle cell allele protection against malaria and CCR5 deletion protection against HIV. Such genetic differences can lead to insights on pathogenesis, drug targets (e.g. CCR5 inhibitors), and more personalized care. For influenza, common genetic variation has been most convincingly shown to influence flu severity at a single locus (IFITM3) that regulates a single step (cytosolic entry) in the complex influenza life cycle. We hypothesize that other human genetic differences affect influenza infection and can be identified through measuring inter-individual variation in cellular infection phenotypes. To facilitate identification of SNPs that affect cellular infection phenotypes, we developed and validated a cell-based GWAS approach called Hi-HOST. SNPs identified as important for influenza infection by Hi-HOST can then be examined for relevance in human infection using already completed human flu challenge studies and population-based studies. We propose that the intersection of human subject and cell line data facilitates discovery of novel pathways and genetic determinants of susceptibility. This project will generate a high resolution analysis of how human genetic variants impact transcription, cellular phenotypes, and human disease following influenza exposure. We will accomplish this through 1) identifying human SNPs that confer resistance/susceptibility to cellular and molecular phenotypes of flu infection, including entry, replication, cell death, cytokine levels, and host transcriptional responses, 2) determining the impact of SNPs on host transcription during influenza challenge of healthy volunteers, and 3) integrating the generated cellular and human challenge datasets to generate and test hypotheses linking transcriptional response and cellular susceptibility. Understanding these differences could lead to new diagnostic approaches in identifying at-risk individuals and novel therapeutic strategies for treatment.",,2023,Duke University,195374,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22968,1R42AI155039-01A1,Development of 4-(aroylamino)piperidine-based entry inhibitors as anti-influenza therapeutics,"Influenza A viruses belong to the orthomyxoviridae family, and have a negative-sense, segmented RNA genome, which can cause seasonal or pandemic flu with high morbidity and significant mortality. Vaccination is the most prevalent prophylactic means for controlling influenza infections. However, an effective vaccine usually takes at least six months to develop. Furthermore, vaccination has limited effectiveness in the treatment of immunocompromised patients, and its effectiveness is also limited during a pandemic. The current therapeutic options for flu infections are all based on the neuraminidase inhibitors (NAIs; oseltamivir, zanamivir and peramivir), while the influenza M2 ion channel blockers (amantadine and rimantadine) are not now recommended since all of the circulating influenza strains have acquired resistance. (Xofluza, a polymerase acidic endonuclease inhibitor, has just been approved in 2018 and is yet untried during a flu season.) The rapid emergence of the NAI-resistant strains of influenza A viruses strongly suggests that NAIs alone may not be sufficient as effective therapies, and thus new treatment options targeting the other viral/host factors are urgently needed. This application defines a plan to develop potent, small molecule inhibitors, which block entry of influenza A viruses. We have identified compounds that inhibit entry of infectious influenza A viruses, with IC50 values in the nanomolar range. We have synthesized structurally diverse analogs of the anti-influenza hit series using structure-activity relationships (SARs) to improve potency and selectivity; validated the lead inhibitor candidates in the infectious assay and investigated the mechanism of action (MOA) of the these inhibitors; and selected anti-influenza inhibitors with excellent in vitro potency and selectivity values and druglike in vivo pharmacokinetic properties. In this Fast Track STTR Phase I &II application, we propose four specific aims: (1) optimize the lead scaffold and select development candidates; (2) investigate the mechanism of action (MOA) of the advanced lead compounds with HA proteins; (3) evaluate the pharmacokinetics/toxicokinetics of the advanced lead compounds; and (4) preclinical development.",,2022,"CHICAGO BIOSOLUTIONS, INC.",300000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P22969,1R01AI144798-01A1,Pandemrix and T Cell Immunology in Narcolepsy,"ABSTRACT: Genetic studies indicate a strong (97%) association of narcolepsy with HLA-DQA1*01:02/DQB1*06:02 (DQ0602), weaker associations with HLA-DP and class I HLA- A*11:01, and effects in other immune related genes such as the TCR αβ loci. The disease is caused by the loss of hypocretin (HCRT)/orexin neurons, as loss of HCRT or HCRT receptors recapitulates symptoms in animal models. Results from our laboratory and from others indicate that a critical step in the disease process is a CD4+ T cell autoimmune response targeting HCRT itself, notably a DQ0602 restricted response to the amidated, C-terminal end of secreted HCRT peptides (HCRTNH2). Indeed, increased T cell response to HCRTNH2 presented by DQ0602 is observed in narcolepsy (our observation), followed by a broader CD4+ T cell responses to other HCRT fragments presented by other HLA class II molecules (other investigators), a result of epitope spreading. This is likely followed by a CD8+ T cell response to HLA class I presented antigens that results in hypocretin cell death and life-long narcolepsy. Unique to narcolepsy, a known environmental factor, the flu, has been associated with initiation of the autoimmune process. Indeed, an increased incidence of narcolepsy in children has been observed following the 2009-2010 pH1N1 Influenza pandemic in China and following vaccination with Pandemrix (GSK), an AS03 adjuvanted pandemic H1N1 2009 (pH1N1) vaccine, but not other vaccines. These observations indicate that epitopes within the pH1N1 virus and vaccine can precipitate narcolepsy in some individuals, findings substantiated by the fact narcolepsy patients have increased T cells binding NP17-31 and pHA273-287, a flu hemagglutinin fragment with significant HCRTNH2 sequence homology. This mechanism is also supported by our preliminary data suggesting TRAJ24 and TRBVB4-2 involvement in pHA273-287, NP17-31 and HCRTNH2 TCR responses, as these TCR segments are modulated by SNPs associated with narcolepsy. In this application, we will further characterize antigenic differences in Pandemrix, Arepanrix and Focetria, vaccines used in the 2009-2010 pH1N1 vaccination campaign, capitalizing on the observation that they have differential risk for precipitating narcolepsy. Our hypothesis, supported by preliminary data, is that Pandemrix contains more pHA273-287 peptide, the main mimic of HCRTNH2 autoimmune responses. In addition, we will continue isolation and characterization of Pandemrix/H1N1 reactive and HCRTNH2 DQ0602 restricted CD4+ T cells. Our hypothesis is that we will ultimately discover pHA273-287/HCRTNH2 and other flu/HCRT cross-reactive cells that use TRAJ24 and TRBVB4-2 segments. Finally, we aim to characterize the phenotype of the corresponding pathogenic cells through single cell sequencing. This high impact study is expected to eventually lead to a) demonstration of molecular mimicry in narcolepsy and b) improved safety of influenza vaccines.",,2025,Stanford University,537390,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P22970,5R43AI152652-02,Development of a Universal Influenza Vaccine,"ABSTRACT Influenza virus (flu) ranks highest in disease burden of all infectious diseases as measured in disability-adjusted life years. Seasonal epidemics cause 200,000-500,000 worldwide deaths annually. The total economic burden of seasonal flu is estimated to range from approximately $26B to $87B each year in the US in terms of direct medical expenses and lost work and productivity. Additionally, at least six known flu pandemics have become global human catastrophes, most notably the Spanish Flu pandemic of 1918, which killed 3-5% of the world’s population. Any reduction in the infection rate, transmission, and severity of flu infection would greatly reduce our healthcare expenditures and improve the quality of life for millions of people every year. The current vaccines are formulated annually based on predictions of which circulating flu strains may be prevalent in a given season. The effectiveness of these vaccines varies from year to year based on the circulation of unexpected antigenic variants and other factors. Vaccine design is complicated the by the multiplicity of flu strains, each with rapidly-evolving dominant antigen epitopes (“decoy” epitopes) that largely stimulate strain- restricted immunity. One strategy for rational antigen design, termed Immune Refocusing Technology (IRT), involves introducing mutations that reduce the immunogenicity of these decoy epitopes thus shifting the immune response to target more widely-conserved subdominant epitopes. BMI has previously applied this IRT approach with some notable successes to other viral antigens (e.g. HRV and the RSV F protein), and we now focus on the major flu surface antigen glycoprotein HA using H1, H3, and B vaccine strains as parental antigens. The anticipated effort to design a suitably modified antigen would ordinarily involve a protracted process of trial-and-error testing of many potential candidates. However, we have recently developed the ANATOPE automated B cell epitope prediction software package with algorithm parameters tuned using methods in artificial intelligence. Our algorithm identifies epitopes with a significantly higher success rate than previously available prediction programs. This breakthrough allows us to assign immunogenicity “strength” scores to particular antigen surface patches and will further guide and accelerate the design of mutant antigens that refocus the immune response to cross-strain conserved epitopes. In this application, we propose to engineer and test the immunogenicity of rationally-designed HA antigens containing mutations that both 1) dampen the immunogenicity of dominant strain-restricted decoy epitopes and 2) enhance the immunogenicity of conserved subdominant epitopes associated with broadly neutralizing antibodies. Follow- up studies will assess the rationally-designed antigens in a ferret challenge study and prepare the approach for translation into humans as a universal vaccine that does not require annual reformulation.",,2022,"BIOLOGICAL MIMETICS, INC.",299218,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3 | Other,Unspecified,,Unspecified,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22971,5R01HL146479-02,Immune mechanisms of influenzaÃÃ'¢ÃÂ'Ã'€ÃÂ'Ã'induced exacerbation of atherosclerosis,"Immune mechanisms of Influenza-induced exacerbation of atherosclerosis Influenza A infection is a significant cause of mortality and morbidity worldwide. It is estimated that 3-4 million cases of severe illness and 300,000 deaths due to influenza infection occur annually. During influenza pandemics, the focus is on lung disease, which is the most common cause of death. However, recent epidemiological studies reported significant mortality associated with cardiovascular diseases (CVD) during influenza infection. Atherosclerosis is a common cause of coronary artery disease (CAD), including MI, stroke, and heart failure. The innate and adaptive immune response to modified lipids and vascular endothelial cells causes a series of events that result in plaque formation in medium to large-sized arteries. If inflammatory stimuli continue, plaques become vulnerable to rupture and can cause MI. However, the mechanism involved in the influenza-induced increase in MI incidence is not clear. Our long-term research goal is to understand the impact of lung-vascular interactions in atherosclerosis. The objective of this application is to determine how influenza infection directly or indirectly impacts the outcome of atherosclerosis. In Aim 1, we will characterize myeloid and lymphoid cellular subsets from lung, aorta, and spleen at various time points (early, peak, recovery phase) after fluorescent-labeled (Color-flu) influenza infection to track influenza virus along with the cellular recruitment to the vessel. We will then examine whether antigen presentation is impacted by oxidized LDL (oxLDL) using bone marrow dendritic cells (BMDCs) and T cell re- stimulation in vitro. In Aim 2, we will determine the role of type III IFNs (IFNÃŽÂ>>) systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza-induced exacerbation of atherosclerosis. Further, we will determine the effect of IFNÃŽÂ>> on foam cell formation in macrophages. Finally, we will determine the effect of conditioned media from influenza or type I (IFNβ), type II (IFNγ), and type III (IFNÃŽÂ>>)-treated human bronchial epithelial cells (HBE) on human primary aortic endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. In Aim 3, we will determine the effect of IL-17 neutralization systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza induced-exacerbation of atherosclerosis. Further, we will determine the effect of lung epithelial IL-17RC signaling during influenza infection in atherosclerotic Apoe-/- mice. Finally, we will determine the effect of conditioned media from influenza- infected or IL-17-treated human bronchial epithelial cells (HBE) on vascular endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. At the completion of these studies, we expect to have made mechanistic insights into the cellular trafficking, viral trafficking, systemic and local effects of IFNs and IL-17, and pulmonary epithelial IL-17 signaling in influenza-induced exacerbation of atherosclerosis that may help to identify immune-based therapeutic targets.",,2025,University Of Pittsburgh At Pittsburgh,389555,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +P22972,5R01AI154470-02,Immunobiology of Influenza Virus-related Critical Illness in Young Hosts,"ABSTRACT Influenza virus is a persistent global menace that every year infects an estimated 5-10% of adults and 20-30% of children worldwide causing over 500,000 influenza-related deaths. Most annual influenza infections are in the very young, the elderly, and in individuals with chronic health conditions such as asthma. However, recurrent influenza pandemics caused by the emergence and spread of highly pathogenic novel influenza A strains, such as occurred in 2009, disproportionately causes severe illness in healthy children and younger adults. This study of life-threatening influenza virus lower respiratory tract infection (LRTI) in young hosts is designed by an established multidisciplinary group of investigators to better understand how host innate and adaptive immunity to influenza virus is associated with disease susceptibility, severity and clinical outcomes. In the Pediatric Intensive Care Influenza (PICFLU1) study, we hypothesized that infection with the influenza virus triggers hypercytokinemia and immune dysregulation in a genetically susceptible host resulting in severe life-threatening infection. Confirming our hypothesis, in PICFLU1 (AI084011, enrolling 2008-2016), we identified a hyperinflammatory phenotype coexisting with innate immunosuppression; both were associated with mortality. We also identified associations between functional variants in IFITM3 and MBL2 with pediatric influenza-related death. In the Immunobiology of Influenza Virus-Related Critical Illness in Young Hosts study (PICFLU2, enrolling 2020-2025), we test the hypothesis that distinct severe influenza LRTI phenotypes â€Â"" defined by host immunobiology â€Â"" can be identified for targeted preventive and therapeutic interventions. In this study we aim to: 1. Identify biomarkers in children with severe influenza LRTI that can be used for prognostic stratification and predictive enrichment in future immunomodulatory clinical trials; 2. Determine if pre-existing strain specific immunity to influenza virus protects against life-threatening disease and influences viral shedding and disease severity; and 3. Identify genes essential for anti-viral immunity and/or containment that explain host susceptibility to severe influenza infection or its outcome. To achieve these aims, we will enroll 600 additional children and young adults with confirmed influenza infection (300 intensive care unit and 300 ward or outpatient) across 35 PICFLU sites. Across PICFLU studies (2008-2025) we will have DNA on ~1,000 young hosts infected with influenza virus to identify important endophenotypes for risk stratification and predictive enrichment in future clinical trials targeting prevention of and more rapid recovery from severe influenza-related disease. Identified influenza virus susceptibility and severity genes are potential “druggable targets” for immune modulation. Our findings could personalize the care of young individuals with severe influenza infection based on distinct immunobiologic host phenotypes based on patient age, influenza strain, clinical presentation, innate and adaptive immune biomarkers and host genetics.",,2024,BOSTON CHILDREN'S HOSPITAL,1143757,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2020 +P22973,5U01AI150747-02,DYNAMICS AND EVOLUTION OF IMMUNE RESPONSES TO INFLUENZA VIRUSES,"PROJECT SUMMARY/ABSTRACT Our goal is to develop a quantitative framework for the generation, boosting and maintenance of immunological memory. Mathematical models are useful because immunization and infection involve the interaction of rapidly changing populations of virus and multiple populations of immune cells. We first develop and validate models using experiments in mice. We then use these validated models to analyze data from human vaccination studies. Aim 1 asks how prior immunity affects and potentially limit the boosting of immunity and apply this to influenza. Our approach is to develop models to understand why prior immunity limits boosting of antibodies to conserved regions of the virus. Specifically, we use our models to better understand how prior immunity might limit boosting of antibody responses to conserved regions on the stem of the hemagglutinin molecule that is the focus of universal influenza vaccines. Aim 2 considers the factors that affect the durability of humoral immune memory, and address questions such as why memory generated by immunization with protein antigens is less durable than immunity generated by virus infection, and how prior immunity can differentially affect the boosting and generation of memory to new strains of influenza. Aim 3 considers the generation of CD8 T cell memory to influenza and yellow fever. We will determine how repeated exposure to influenza affects the diversity of the CD8 T cell responses generated. We have access to a unique dataset that follows the number of YFV-specific CD8 T cells, changes in their phenotype, and their turnover from heavy water labelling studies for a period of over one year. Our analysis of this dataset will allow us to address an ongoing controversy regarding whether are long-term memory CD8 memory stem cells are generated rapidly after immunization or only gradually over time. Aim 4 describes computational tools that we will build for B cell receptor sequence analysis and visualization, and for simulation of the dynamics of immune responses. These tools will be widely accessible online, and promoted at workshops and scientific symposia we organize.",,2025,EMORY UNIVERSITY,1190313,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +P22974,1K99AI159136-01,Investigating the development and clonal dynamics of broadly neutralizing B cells against influenza viruses,"PROJECT SUMMARY/ABSTRACT Broadly neutralizing antibodies against the influenza virus surface glycoprotein hemagglutinin (HA) can provide protection from nearly all influenza viruses. However, broadly neutralizing antibodies are rarely induced by vaccination and instead, most antibodies target variable epitopes of the influenza virus HA head domain that only provide narrow protection against a few influenza virus strains. The fundamental mechanisms dictating B cell immunodominance, which B cell specificities are recalled upon virus exposure, remain largely unknown. We identified that first exposure to a novel influenza virus robustly induced antibodies against four broadly neutralizing epitopes of HA. However, repeated exposure to the same virus preferentially drove the recruitment of antibodies targeting variable epitopes of the HA head. Notably, my studies identified that antibodies targeting broadly neutralizing epitopes are enriched for polyreactivity, the ability of a single antibody to bind to multiple molecularly distinct antigens, including foreign and self-antigens. Furthermore, polyreactive naïve B cells targeting broadly neutralizing epitopes are preferentially selected into the memory B cell pool to provide defense against novel pandemic-threat influenza viruses. Based on my preliminary data, I hypothesize that HA epitope specificity influences B cell development, differentiation, and inter-clonal competition, which leads to differences in B cell immunodominance. B cell immunodominance may be dictated by three independent processes: 1) B cells targeting broadly neutralizing epitopes may undergo clonal deletion or become anergic as a result of being polyreactive (Aim 1), 2) B cells targeting broadly neutralizing epitopes differentiate into short-lived B cell subsets as opposed to long-lived B cell subsets (Aim 2), and 3) B cells targeting variable epitopes outcompete B cells targeting broadly neutralizing epitopes (Aim 3). To test these aims, I will use CRISPR/Cas9 to generate B cell receptor knock-in mice expressing the germline version of human monoclonal antibodies targeting four broadly neutralizing epitopes of HA and two variable epitopes of HA. To test Aim 1, I will evaluate B cell development and B cell signaling potential of each B cell receptor knock-in line by generating mixed bone marrow chimeras. In Aim 2, I will determine if epitope specificity shapes B cell differentiation potential by immunizing mice that receive a B cell adoptive transfer from each B cell receptor knock-in line and tracking B cell differentiation and affinity maturation. In Aim 3, I will determine whether B cells targeting a variable epitope outcompete B cells targeting a broadly neutralizing epitope within the germinal center by tracking germinal center responses in HA- immunized mice that have received adoptively transferred B cells targeting each epitope. Knowledge gained from this research will provide critical insight into how broadly neutralizing B cells can be induced, which will aid in the development of a universal influenza virus vaccine that can provide broad protection against all influenza viruses. The additional training afforded by this mentored award will enable me to expand my scientific and professional skillsets, leading to my research independence and successful transition into a faculty position.",,2022,University Of Chicago,103503,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P22976,1R21AI160779-01A1,Dissecting ADP-ribosylation as an innate immune response countering influenza virus replication,"ABSTRACT Viral infections manipulate diverse post-translational modifications (PTMs), altering existing protein landscapes to create cellular environments favorable to replication. PTMs allow for rapid modulation of host environments by altering protein abundance, localization, and activity. Because of their dynamic nature, PTMs typify ideal immune response effectors or initiators. Our data identifies ADP-ribosylation, the modification of proteins with ADP-ribose (ADPr), as a rapid, immune-like response from infected cells that constitutes an antiviral response that counters influenza virus infection. Using cutting-edge ADPr-specific mass spectrometry approaches, we have characterized with single amino acid resolution the ADP-ribosylome during influenza virus infection and identified thousands of modifications on viral and host proteins. ADP-ribosylation has been associated with antiviral responses against multiple viruses. However, little is known about how viral infections trigger this response or the activiral mechanism(s) of ADP-ribosylation and poly(ADPr)-polymerases (PARPs), the enzymes that catalyze addition of ADPr to proteins. Here, we propose studies of ADP-ribosylation during influenza virus infection. We will identify the functional consequences of specific ADPr modifications, and building on our unique ADP-ribosylome dataset, investigate how ADP-ribosylation alters the function of specific viral and host proteins. We will interrogate the cellular pathways responsible for initiating ADP-ribosylation responses, defining the molecular triggers and PARPs that are activated during influenza virus infection. These experiments will elucidate the mechanisms of ADPr-mediated viral inhibition, the factors that trigger this response, and how viruses counter it, establishing ADP-ribosylation as a key aspect of cellular antiviral responses and perhaps as an entirely independent arm of antiviral defenses.",,2023,UNIVERSITY OF WISCONSIN-MADISON,248446,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P22981,1U01IP001136-01,Modeling toolkit to evaluate multifaceted control strategies for seasonal and pandemic influenza,"PROJECT SUMMARY We will develop a data-driven model of seasonal and pandemic influenza transmission throughout the US to accelerate robust assessments of multifaceted influenza intervention strategies. We will work closely with the CDC Modeling Network to advance the fidelity, transparency and translation of models as an evidence base for influenza policy making, prevention and control. This project extends a metapopulation model of influenza transmission within and between 217 major metropolitan areas in the US that we are developing in collaboration with the CDC Modeling Network. The model includes travel between cities, age- and risk-group specific susceptibility, probability of clinical outcomes, intervention efficacies and uptake rates, as well as the impacts of local climate and school calendars on transmission rates. Using a range of public health, epidemiological, societal and economic metrics, the model can flexibly evaluate thousands of candidate intervention strategies, including time- and location-based combinations of vaccines, antivirals, and social distancing measures with potential subgroup-specific prioritization. Our proposal includes four major aims. In Aim 1, we will extend our US Influenza Model to include the co- circulation of multiple viruses competing via transient heterosubtypic immunity. We will derive new estimates for the duration and magnitude of heterosubtypic immunity and design strain-specific strategies for effectively controlling co-circulating seasonal and pandemic influenza viruses. In Aim 2, we will evaluate intervention strategies that leverage newly approved and combined antiviral drugs. We will fit within-host viral dynamic models to clinical data on new antivirals to estimate the efficacy of various drug regimens in different subpopulations with respect to disease severity, infectiousness, and the risk of antiviral resistance. In Aim 3, we will build a granular within-city model of influenza transmission based on abundant data and local collaborations with public health and healthcare leaders in the Austin-Round Rock Metropolitan Area. We will apply the model to elucidate socioeconomic and geographic disparities in influenza risk and design interventions that ameliorate such gaps. In Aim 4, we will build an interactive visualization platform that allows users to specify epidemic scenarios, implement layered interventions as simulations unfold, and view the model dynamics through the lens of a surveillance module based on the CDC’s FluView Interactive portal. We will work extensively with the CDC Modeling Network to build a diverse portfolio of validated models and best practices for collaborative decision support. Our projects will contribute flexible models for the evaluation of multifaceted influenza interventions, elucidate competition among influenza viruses and the efficacies of novel antivirals, and provide insights into socioeconomic disparities in influenza burden. Furthermore, our innovative visualization tool will broadly support the translation of science to public policy.",,2025,University Of Texas At Austin,374998,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Research to inform ethical issues,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Research to inform ethical issues related to Public Health Measures,2020 +P22982,1U01IP001141-01,Individual-based Simulation of Seasonal and Pandemic Influenza Epidemics,"Project Abstract Seasonal influenza caused an estimated 48.8 million illnesses, 22.7 million health care visits, 959,000 hospitalizations, and 79,400 deaths in 2017-18. Influenza is a particularly complicated disease to prevent as the influenza virus itself changes over time, and unlike vaccinations for measles or hepatitis B, the effectiveness of annual vaccination may be limited if the particular strain that appears in an outbreak is not represented in the vaccine. In addition, the immunity produced by vaccination declines over time, and many individuals, especially the elderly, may lose protection toward the end of an influenza season. The goals of iMPH: Influenza Modeling for Public Health are to bring together four experienced modeling groups including the Public Health Dynamics Laboratory (PHDL) that has significant experience as a MIDAS Center of Excellence in the agent-based modeling of influenza, the Pittsburgh Vaccine Research Group (PittVax), vaccine policy experts who are site leads in both the inpatient and outpatient CDC influenza vaccine effectiveness (VE) networks, the DELPHI (Developing the Theory and Practice of Epidemiological Forecasting) group at CMU, the most accurate US influenza prediction group, and the current MIDAS Network Coordination Center (MCC) that brings major data and model coordination expertise. Our specific Aims are to create realistic, biologically based models of influenza, including the development and maintenance of immunity over time through either the development of the disease or vaccination so that we can test the benefit of different prevention strategies in seasonal or pandemic influenza. Specifically, we will examine strategies such as: enhanced vaccines that create high initial antibody levels, the addition of a second, mid-season vaccine, or potentially delaying vaccination in some individuals until later in the season. We will also examine the effectiveness of vaccination policies over a multi-year time, such as different vaccinations for individuals who have had previous influenza, and consideration of every-other year vaccines, Finally we will examine community-level interventions, such as school closures and working from home to impact the spread of influenza over a season. As a CDC Influenza Modeling Center, we will also collaborate with other centers to develop rapid responses to current influenza threats, to share data, models and results to provide higher confidence to the CDC that model-based recommendations can be used to formulate local, state and national influenza policy.",,2025,University Of Pittsburgh At Pittsburgh,374898,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control | Policies for public health, disease control & community resilience",Disease models | Immunity | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P22983,3UM1AI148576-01S2,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2020,Emory University,11432119,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P22984,1R43AI149987-01A1,SBIR Phase I: Hemagglutinin-specific affinity capture membrane for rapid purification of influenza vaccines,"Project Summary This SBIR Phase I project will develop a novel affinity membrane to address key purification challenges for producing highly pure and effective recombinant hemagglutinin (rHA) influenza vaccines. In the U.S. each year, from 5 to 20 percent of the population becomes ill with influenza. Worldwide, there are about 3 to 5 million severe cases and up to 500,000 deaths yearly. Hemagglutinin (HA) is the primary protein in the influenza vaccines responsible for producing an immune response. Due to its short production time (e.g. one month) compared to that of cell-based and egg based-vaccines (e.g. three to six months), rHA vaccines show great promise to rapidly respond to pandemic influenza strains. However, there is a lack of a high-affinity purification technology for rHAs. Currently, time consuming and multiple low-affinity downstream purification steps are used to obtain sufficient purity for commercial manufacturing. The goal of this SBIR Phase I project is to demonstrate the feasibility of developing high-capacity affinity membranes for the rapid, selective purification of HA. Products derived from this innovation will be first-in-market, disposable membrane chromatography columns that can simplify and improve the recombinant vaccine purification process by offering increased affinity, purity, and recovery over conventional methods. The aims of the Phase I study are (1) to demonstrate the feasibility of synthesizing HA affinity membranes and (2) to test prototype membrane chromatography columns for capture purification of recombinant HA vaccines and benchmark their performance against existing technology. In Specific Aim 1, we will evaluate the roles played by synthesis conditions and bind-and-elute buffer conditions on performance using high-throughput experiments. In Specific Aim 2, Purilogics will collaborate with researchers at Sciogen, LLC to quantify and benchmark performance for purification of recombinant HA vaccines prepared by Sciogen from cell supernatant. Multiple iterations of synthesis and performance characterization will improve membrane performance. In Phase II, Purilogics plans to (i) establish a scalable process to produce prototypes for comprehensive performance testing, determining sterilization protocols, product shelf life, and reusability; (ii) conduct field research with industrial partners who are potential customers; and (iii) test the hypothesis that the receptor-based purification can improve vaccine effectiveness through animal studies. Market entry for the new column products will be sales to purification scientists and engineers in biopharmaceutical companies. The estimated total addressable market for prepacked, disposable HA affinity chromatography columns under development by Purilogics is expected to be > $280M by 2023.",,2021,"PURILOGICS, LLC",251170,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration,2020 +P22985,1R13AI154682-01,The 20th Annual Meeting of the Rocky Mountain Virology Association,"The Rocky Mountain Virology Association will hold its 20th annual meeting in October 2020. The meeting brings together regional and national investigators in virology and prion biology for a 3-day retreat- style conference with extensive interaction and collaboration. The original meeting was organized by investigators in Colorado and Wyoming who were interested in the free and open exchange of scientific data and ideas concerning general virology in a venue that promotes collaboration among students, post-doctoral researchers and faculty members. Specifically, our annual meeting at the Mountain Campus of Colorado State University encourages young scientists to present their research and receive feedback from established scientists. The goals are promotion of scientific interactions and training. A major benefit of participation has been the novel collaborations that arise between scientists in different disciplines, i.e. RNA stability and Flavivirus biology. The topics discussed include medical virology (vaccines, epidemiology, viral zoonoses), arthropod-borne diseases (RNA viruses and RNA metabolism, viral vectors and vector biology), host defenses (viral immunology and pathogenesis), prion biology, and cancer biology. Special sessions on HIV pathogenesis, vaccine development, pandemic influenza, prions, virus discovery and the global impact of viral diseases have been featured at past meetings. The next meeting will feature perhaps the most disparate, yet now intimately tied fields, epidemiology and epigenetics. This meeting offers extravagant collaborative opportunities. The attendees include scientists from Colorado State University, The University of Colorado, the University of Wyoming, the University of Northern Colorado, the Centers for Disease Control (Fort Collins) and the Department of Agriculture Animal and Plant Health Inspection Service as well as scientists from regional biotech companies, and universities in Iowa, Idaho, Nebraska, Kansas, Montana and Utah. The Rocky Mountain Virology Association was incorporated in 2010 as a tax-exempt educational charity (Section 501(c)(3)). Our board of directors is charged with encouraging student and junior faculty involvement by minimizing costs as we encourage women and minorities to participate in all stages of program presentation and development. Everyone involved in programming is a volunteer. Our attendance is now limited by the venue to a maximum of 124 individuals. The growth of the meeting to capacity over the last three years is welcome; It illustrates a strong desire on the part of regional scientists to participate, but the continued growth in regional and national interest may require increased frequency or larger venues. Any expansion will focus on maintaining a cloistered scientific environment to maximize effective collaborative interactions in an inspirational environment. Funds for this proposal are requested to provide minority grants and childcare, reduced registration fees for graduate students, post-doctoral fellows and early-stage investigators, and for travel and housing for seven invited speakers. Registration fees, charitable contributions, and sponsorships cover the base costs for the meeting. The RMVA has been a source of communication and collaboration for the Rocky Mountain region, with outreach across the nation, for nineteen years. The Rocky Mountain region is very large geographically and research and education in the virology has significantly increased over the last few years. Our efforts and NIAID support have expanded interest in this meeting beyond the region to national and international levels to the benefit of the regional students and investigators and to the health and wellbeing of the nation.",,2021,ROCKY MOUNTAIN VIROLOGY ASSOCIATION,3310,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Health Systems Research,Health information systems,2020 +P22986,1U01IP001137-01,FluMod - Center for the Multiscale Modeling of Pandemic and seasonal Flu Prevention and Control,"PROJECT SUMMARY In this proposal we plan to contribute addressing the above foundational and operational challenges by advancing the science of influenza modeling and contributing novel methods and data sources that will increase the accuracy and availability of seasonal and pandemic influenza models. To address these challenges, we plan to build on the unique mechanistic spatially structured modeling approaches developed by our consortium, that includes stochastic metapopulation models and fully developed agent-based models nested together in our global epidemic and mobility modeling (GLEAM) approach. The objective of this project is to generate novel and actionable scientific insights from dynamic transmission models of influenza transmission that effectively integrate key socio-demographic indicators of the focus population, as well as a wide spectrum of pharmaceutical and non-pharmaceutical interventions. Our proposed work in specific aim 1 (A1) will leverage our global modeling (from the global to local scale) framework that can be used to explore the multi-year impact of influenza vaccination, antiviral prophylaxis/treatment, and community mitigation during influenza seasons and pandemics. Our specific aim 2 (A2) will focus on using high quality data to model heterogeneous transmission drivers and novel contact pattern stratifications that will allow us to guide mitigation strategies and prioritization for interventions. In our Aim 3 (A3) we will use artificial intelligence approaches to identify interventions that are particularly synergistic and well-suited to particular epidemic scenarios, for seasonal and pandemic influenza. Our overarching goal is to provide a modeling portfolio with flexible and innovative mathematical and computational approaches. We aim to address several questions commonly asked about seasonal and pandemic influenza and match these with analytical methods and outbreak projections. The modeling and data developed in this project can help facilitate and justify transparent public health decisions, while contributing to the definition of standard methods for model selection and validation. Finally, our influenza modeling platform can also benefit the broader network of modeling teams and can be used to improve result sharing and harmonization of modeling approaches.",,2025,Northeastern University,371721,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P22987,3UM1AI148576-01S1,Vaccine and Treatment Evaluation Units,"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC). The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention.",,2021,Emory University,5485363,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P22988,6U01IP001136-01M001,Modeling toolkit to evaluate multifaceted control strategies for seasonal and pandemic influenza,,,2025,University Of Texas At Austin,399699,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Research to inform ethical issues,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Research to inform ethical issues related to Public Health Measures,2020 +P22989,75N93020C00041-0-9999-1,SBIR TOPIC 081: ADJUVANT DEVELOPMENT FOR VACCINES AGAINST INFECTIOUS OR IMMUNE-MEDIATED DISEASES,"This contract is part of the NIAID Adjuvant Development program, which supports the preclinical development of novel vaccine adjuvant candidates. The goal of this contract is to support the further development of the ASP-1 adjuvant within the context of a vaccine to protect against influenzas.",,2022,"CELDARA MEDICAL, LLC",599977,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P22990,6U01IP001141-01M001,Individual-based Simulation of Seasonal and Pandemic Influenza Epidemics - supplement Emergency Response to the COVID-19 Pandemic,,,2025,University Of Pittsburgh At Pittsburgh,399999,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Immunity | Disease models | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P22991,1U19AT010838-01,Examining the Effects of Immulina to Increase Immune Resilience against Influenza Virus Infections,"PROJECT 2: ABSTRACT/SUMMARY The proposed University of Mississippi (UM) Botanical Dietary Supplements Research Center (BDSRC) is focused on filling in knowledge gaps related to the potential for the Spirulina-based product, ImmulinaTM, to promote resilience against and/or recovery from influenza and, by extension, other respiratory viral infections. During the 2017-18 reporting year in the U.S. alone, influenza resulted in 959,000 patient hospitalizations and 79,400 deaths. The UM BDSRC will be composed of an Administration Core, a Botanical Core, and two research projects. Project 2, Evaluation of ImmulinaTM Oral Supplement for Host Resistance to Influenza Virus Infection, will be directed by Gailen Marshall, MD, PhD, Professor and Executive Director of the Mississippi Clinical Research and Trials Center at UM Medical Center. Working closely with him will be Khalid Ashfaq, PhD, DVM, DTVM. Project 2 is designed to include studies utilizing both mouse models (Years 1-2) and biomarker-based human models (Years 3-5) aimed at establishing the impact of ImmulinaTM supplementation on increasing host resilience against the pathogenic effects of influenza virus infection. It will investigate the following hypothesis: ImmulinaTM given in its optimal oral form will alter the host antiviral immune response, manifested by increases in NK cell numbers and/or activity, anti-flu H and N antibody titers, and CD8+ cytotoxic T lymphocytes (CTL) against flu-infected cells. To investigate our hypothesis, we will achieve the following specific aims: 1. Evaluate oral administration of ImmulinaTM in three non-lethal mouse models of resilience against influenza A virus infection (prophylaxis, prodrome and recovery) to determine the most effective utility of ImmulinaTM for enhancing host immunity to improve antiviral resilience; 2. Confirm that activation of the TLR2 signaling pathway by Braun-type lipoproteins is a primary causal mechanism through which ImmulinaTM enhances host immunity against antiviral infection; 3. Determine the optimal form and dosage of the ImmulinaTM-based supplement in the human model that will maximize effects on increasing NK cell numbers and/or activity, increased supporting cytokines (IL-15, IL- 2, IGNg), influenza-specific antibody titers and CTL numbers; 4. Establish the timeline for optimal NK, cytokine, antibody and CTL responses in terms of both initial changes and maximal changes and duration of the change once the ImmulinaTM is discontinued in normal and immune compromised (elderly) human research participants; and 5. Examine the effects of routine influenzas vaccine given before, during, or after ImmulinaTM use to investigate influenza antigen-specific immune responses in individuals receiving ImmulinaTM supplement vs placebo.",,2025,University Of Mississippi,423031,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P22993,1R41AI149954-01,"An adjuvanted influenza vaccine platform for dose sparing, multiplexing, and rapid deployment","Abstract Influenza is the cause of considerable morbidity and mortality globally. Certain groups, i.e., infants, pregnant young women, and older adults are especially at risk for severe disease. Despite immunization being the most effective and economical prophylactic approach, vaccines often provide less than optimal defense against an influenza illness, with efficacies ranging from 10-60%. This inadequate vaccine efficacy is mainly due to the high mutation rate (antigenic drift), or reassortment (antigenic shift) of the surface influenza molecule hemagglutinin (HA) which is the primary target of influenza vaccines. As a result, circulating influenza strains may evade the body’s protective antibodies induced by vaccination because the influenza’s targeted epitope may have mutated and no longer be recognized by the antibodies. The vast majority of influenza vaccine doses made today are produced in chicken eggs. This process takes 6-8 months which increases the probability of influenza mutation and the associated decreased in efficacy of the vaccine. This STTR Phase 1 proposal involves the development and characterization of a unique vaccine platform that has been developed by the company POP BIO. This platform consists of fabricating lipid bilayer nanoliposomes with a cobalt-porphyrin moiety intercalated into the bilayer (CoPoP) along with the synthetic monophosphoryl lipid A (PHADÃ'®), a TLR4-based vaccine adjuvant. This prep is then combined with his-tagged recombinant influenza HA. The his-tag stably inserts into the bilayer by association with the cobalt producing nanoliposomes decorated with the immunogenic influenza antigen. The CoPoP/PHAD can be mass produced and stockpiled and the production of the influenza HA antigens can be performed rapidly using standard molecular biology techniques (avoiding the long duration of egg production). At the time of vaccination, the recently produced HA antigens can be added on-site to the CoPoP/PHAD vial to produce the vaccine dose. Shortening the time from HA antigen design to time of vaccination will reduce the probability of virus mutation and thus be more effective. In addition, it has been shown that this platform allows for the use of much less antigen in the vaccine (antigen sparing) and has the capacity for multiplexing with numerous antigens from different influenza strains (expanding its breadth). This study will involve POP BIO producing and characterizing the physical and chemical properties of the CoPoP/PHAD-influenza antigen formulations. The University at Buffalo sub-contracting laboratory will then test them in mice to assess the level of protection against challenge with mouse-adapted strains of influenza. The amount of antigen-sparing will be determined in comparison with other influenza vaccine formulations. In addition, the ability of the CoPoP/PHAD nanoliposomes to accommodate multiple different influenza antigens with associated protection against influenza infection in mice will be assessed. The subsequent STTR Phase 2 proposal will expand development of this platform to novel influenza antigen designs and testing in ferrets in preparation for an IND application.",,2022,"POP BIOTECHNOLOGIES, INC",223797,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P22994,1R21AI152006-01,Assessing Flu-specific Humoral Immunity in Human Lung after Ex Vivo Lung Perfusion,"PROJECT SUMMARY. Broadly reactive humoral immune responses to flu protect against viral variants. Murine data shows that the flu-specific memory B cells (Bmem) in the lung are cross-protective across a number of influenza strains and are functionally distinct from circulating and lymphoid counterparts. As yet we do not know if flu-specific Bmem in the human lung are cross-protective and bridging this knowledge gap is important to design the appropriate vaccine regimens that are universally protective against flu. Flu-specific Bmem in ex vivo lung tissues are rare and this represents a significant technical hurdle in assaying the flu-specific Bmem response in human lung tissues. In order to address this technical hurdle, this application seeks to establish a model system wherein human lung tissue is challenged with influenza virus and maintained viable after this challenge on an advanced cardiopulmonary modality called Ex Vivo Lung Perfusion or EVLP. We anticipate this model will allow us to enumerate and analyze the flu-specific Bmem response at scale in ex vivo human lung tissues. We also anticipate that this model system will allow us to compare binding reactivity to viral variants between flu- specific Bmem located in lung versus mediastinal lymph node tissues to define where cross-protective immunity exists in the respiratory tract.",,2022,University Of Alabama At Birmingham,185625,Human Populations | Viruses | Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity | Disease models",2020 +P22995,1R21AI153673-01,"Elucidating the Mode of Action of ""Tfh-like"" Resident Memory CD4+T cells in Human Lung","Project Summary Influenza infections cause substantial morbidity and mortality worldwide. While vaccination is considered to provide protection, the antibody response induced by current seasonal vaccines is generally short-lived. In contrast, natural influenza infection induces durable protective immunity against future influenza virus infections. The immune mechanisms and pathways that are linked with durable protection by natural infection remain unclear particularly in humans. Studies in animal models show that influenza infection, but not immunization with inactivated virus, generates influenza-specific lung tissue-resident memory T (TRM) cells. TRM are retained for a long time locally, and there is evidence that influenza-specific TRM are far more efficient than their splenic counterpart for protection from influenza infection. Infection with influenza virus also induces lung-resident memory B (BRM) cells that rapidly produce specific Abs in the lung following infection challenge. Whereas these observations suggest a key role of influenza-specific lung BRM at the frontline upon re-infection, the mechanism by which lung BRM differentiate into Ab-producing cells remains unknown. We hypothesize that a subset(s) of influenza-specific lung CD4 TRM display properties similar to T follicular helper (Tfh) cells, and that this subset(s) interact with influenza-specific memory B cells in human lung for rapid local Ab response. In this proposal, we will leverage our extensive expertise in human CD4+ T cell subsets to define a “Tfh-like” subset within human lung CD4 TRM, and determine their mode of action on lung BRM. Aim 1 will define the phenotype of “Tfh-like” CD4 TRM in human lung. By using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we will comprehensively analyze the transcriptional heterogeneity among human lung CD4+ T cells differentially expressing surface markers, and aim to identify the cell population enriched with the Tfh-gene signature. We will also assess the phenotype of influenza-specific CD4 TRM in human lung by using the IRF4 assay that we have recently established. Aim 2 will comprehensively define the subsets of influenza HA-specific B cells in human lung. By co-culturing “Tfh-like” CD4 TRM with lung BRM, we will analyze whether the T cells induce B cell differentiation into influenza Ab-producing cells. We will further determine the helper mechanism by blocking several candidate molecules. As such, our study aims to identify the major T and B cell subsets in human lung responsible for rapid local Ab response. We anticipate that our study will increase our knowledge in the local immune protection mechanism of human lung and provide significant insight into the design of efficient influenza vaccines.",,2021,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,254250,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P22996,1R01HL146479-01A1,Immune mechanisms of influenza-induced exacerbation of atherosclerosis,"Immune mechanisms of Influenza-induced exacerbation of atherosclerosis Influenza A infection is a significant cause of mortality and morbidity worldwide. It is estimated that 3-4 million cases of severe illness and 300,000 deaths due to influenza infection occur annually. During influenza pandemics, the focus is on lung disease, which is the most common cause of death. However, recent epidemiological studies reported significant mortality associated with cardiovascular diseases (CVD) during influenza infection. Atherosclerosis is a common cause of coronary artery disease (CAD), including MI, stroke, and heart failure. The innate and adaptive immune response to modified lipids and vascular endothelial cells causes a series of events that result in plaque formation in medium to large-sized arteries. If inflammatory stimuli continue, plaques become vulnerable to rupture and can cause MI. However, the mechanism involved in the influenza-induced increase in MI incidence is not clear. Our long-term research goal is to understand the impact of lung-vascular interactions in atherosclerosis. The objective of this application is to determine how influenza infection directly or indirectly impacts the outcome of atherosclerosis. In Aim 1, we will characterize myeloid and lymphoid cellular subsets from lung, aorta, and spleen at various time points (early, peak, recovery phase) after fluorescent-labeled (Color-flu) influenza infection to track influenza virus along with the cellular recruitment to the vessel. We will then examine whether antigen presentation is impacted by oxidized LDL (oxLDL) using bone marrow dendritic cells (BMDCs) and T cell re- stimulation in vitro. In Aim 2, we will determine the role of type III IFNs (IFNÃŽÂ>>) systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza-induced exacerbation of atherosclerosis. Further, we will determine the effect of IFNÃŽÂ>> on foam cell formation in macrophages. Finally, we will determine the effect of conditioned media from influenza or type I (IFNβ), type II (IFNγ), and type III (IFNÃŽÂ>>)-treated human bronchial epithelial cells (HBE) on human primary aortic endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. In Aim 3, we will determine the effect of IL-17 neutralization systemically (intraperitoneal) or locally in the lung (oropharyngeal) in influenza induced-exacerbation of atherosclerosis. Further, we will determine the effect of lung epithelial IL-17RC signaling during influenza infection in atherosclerotic Apoe-/- mice. Finally, we will determine the effect of conditioned media from influenza- infected or IL-17-treated human bronchial epithelial cells (HBE) on vascular endothelial cells (HAEC) to identify the mechanism involved in the lung-vascular interactions in atherosclerosis. At the completion of these studies, we expect to have made mechanistic insights into the cellular trafficking, viral trafficking, systemic and local effects of IFNs and IL-17, and pulmonary epithelial IL-17 signaling in influenza-induced exacerbation of atherosclerosis that may help to identify immune-based therapeutic targets.",,2025,University Of Pittsburgh At Pittsburgh,389555,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2020 +P22997,3R01AI132191-04S1,Advancing a broad-spectrum anti-influenza A virus RNA packaging inhibitor to an IND,"Our goal is to leverage our collective academic and industry experience in antiviral research and development to advance an exciting novel inhibitor with broad-spectrum activity against the influenza A virus (IAV) Priority Pathogenâ€Â""towards an IND. Our lead molecule, LNA9, is a short 15 base locked nucleic acid (LNA) “gapmer” that specifically targets an essential IAV packaging signal composed of a unique RNA second- ary structure that we recently discovered and found to be conserved across all examined subtypes of IAV, including 1918 pandemic flu, high path avian (H5N1) and 2009 `swine' (H1N1). LNA9 has a nuclease-resistant phosphorothioate backbone and an internal RNAse H activating sequence that is designed to catalytically disrupt and degrade its target IAV packaging signal. In vitro, LNA9 dramatically inhibits IAV packaging at nM concentrations when added before or after infection, and in vivo, intranasal (IN) administration of LNA9 at -12, 8, and 36 hours post infection completely prevents IAV lethality in mice. We now seek to develop LNA9 into a clinical stage drug by: 1) Further expanding the virology data package by a) demonstrating activity against additional highly pathogenic and drug resistant strains of IAV; b) providing additional evidence for LNA9's high barrier to the development of resistance compared to other direct-acting antivirals in vitro and in vivo; c) determining the minimum in vivo effective dose, and number of days before or after infection that LNA9 administration can rescue from influenza mortality; and d) demonstrating LNA9's efficacy in second validated ferret model, including prevention of transmission: 2) Enabling the optimal delivery and monitoring methods for in vivo preclinical studies by: a) demonstrating the in vivo efficacy of IV delivery to complement the currently proven IN route; b) establishing the analytical methods to monitor the distribution and clearance kinetics of LNA9 following in vivo administration; and c) performing mouse, rat, and dog single dose PK studies via IN and IV routes; 3) Manufacturing LNA9 to support the requisite IND-enabling and initial clinical studies by a) synthesizing 5g of non-GMP LNA9, and 10g of GMP LNA9; and b) performing the final release/stability studies of the product (API); 4) Performing initial in vitro ADME-Tox and preclinical animal safety testing; and 5) Completing the IND-enabling GLP safety pharmacology and multiple dose 14-day escalation rodent and non- rodent toxicity studies, a clinical development plan, and pre-IND meeting package. Our multidisciplinary team--including academics and industry partners with demonstrated expertise in virology, influenza biology, oligonucleotide chemistry, pulmonary formulation and delivery, regulatory affairs, and successful early drug developmentâ€Â""is ideally suited for this proposal. Successful accomplishment of our specific aims will yield an exciting novel drug capable of conferring protection against this key Priority Pathogen, including its most virulent strains that threaten millions.",,2022,Stanford University,745482,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P22998,1R01AI147109-01A1,Rapid Manufacturing of a Universal Flu Vaccine Using TMV-conjugated Centralized Antigens,"Project Abstract This interdisciplinary proposal brings together three highly successful but independent technologies to create an effective and broadly neutralizing universal influenza vaccine. Our approach combines breath of immunity, by using a consensus HA strategy, production speed and capacity by working with Kentucky BioProcessing (KBP), who can express HA protein in plants, and vastly improved subunit vaccine potency using a TMV-HA conjugation approach to create a candidate universal influenza virus vaccine. Based on our preclinical data on three influenza A strains, we expect our approach will drive long term immunity that is balanced between antibody and cellular immunity, providing potential for overlapping mechanisms of immune protection. We bring together a strong team of different disciplines with a combined goal to quickly show proof of concept with H1, H3, H5, and M2e antigens. Our Specific Aims are as follows: 1) Production of TMV-HA conjugates of centralized H1, H3, H5 genes and M2e peptide, 2) Immune response analysis, murine challenge studies and 3) Translational and ferret studies of TMV-HAc and TMV-M2e vaccines. Dr. Weaver has developed a computational method to express an ancestral sequence of HA, representing a consensus of sequences within an Influenza subtype. These vaccines protect against drifted seasonal influenza variants better than a traditional trivalent inactivated virus vaccine. In partnership with KBP, we will use established plant expression methods to produce centralized HA proteins, with the capacity to produce protein for the planned studies and for future clinical trial development. HA consensus protein will be fused to the surface of Tobacco Mosaic virus (TMV) by chemical conjugation, a method developed by Dr. McCormick to improve HA subunit vaccine potency. TMV-HA vaccines will also be combined with a highly conserved M2e peptide vaccine, to broaden protection and reduce vaccine dose. Immunological analysis will be used to confirm vaccine potency, in order to optimize dose, schedule and route of administration. Vaccine efficacy and broadly protective immunity will be confirmed by lethal influenza challenge using 9 divergent virus types in a murine model of disease. Finally, vaccine formulations will be re-tested in ferrets, a models of influenza infection which more closely mimics the progress of disease in humans. Our vaccine is designed to drive local and systemic immunity after either intranasal or intramuscular routes of administration, and we will use immunogenicity and pathogen challenge data to define an optimized single dose vaccine formulation. Our goal is to generate an effective universal vaccine against influenza that can be manufactured at scale, with significant potential for translation into a universal vaccine product that is ready for clinical testing.",,2025,UNIVERSITY OF NEBRASKA LINCOLN,661359,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P22999,1R21AI149648-01,Determine the minimal level of replication required for broad protective immunity of influenza vaccine,"Project Summary Influenza A virus causes disease in 5%-20% of the population with over 200,000 hospitalizations annually in US. The antigen drift and shift of influenza virus due to rapid evolution pose a serious challenge for annual flu vaccination program, which is effective depending on the accurate prediction of the influenza serotypes that will be circulating in the next flu season. The recent failure of influenza vaccine and potential outbreak of influenza pandemics highlights the urgent need for a vaccine that can provide broad protection. Interferon (IFN) is a critical component of the innate immune system and also the bridge between the innate and adaptive immune responses. We recently studied the anti-IFN function of influenza genome using a quantitative and high-throughput genomics system. By incorporating eight IFN-sensitive mutations into influenza genome, we generated a Hyper Interferon Sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in wild type and immune-deficient SCID mice, but fully competent in IFNAR-deficient mice. HIS provides protection against homologous and heterologous viral challenges. Our central hypothesis is that systematical elimination of IFN-evasion functions on multiple segments of the virus genome generates proper induction of innate immune response, which is essential for establishing long term memory B cell response and T cell response by live attenuated influenza vaccine. Our objective is to determine the minimal replication capacity required for live attenuated influenza virus vaccine, identify and generate single-round infection HIS virus, which can induce strong IFNR signaling in vitro, but has no replication capacity in vivo due to innate immune response. Such vaccine virus candidate would have confined one-round infection during immunization whereas the IFN inducing activity would be strong enough to illicit broad protective immunity. We will generate hyper IFN sensitive virus that has no replication capacity in vivo, and characterize its replication kinetics and responsiveness to IFN in lung epithelial cells. After we obtain such virus, we will infect mice with vaccine candidate viruses and characterize the induced immune responses. Finally, we will determine protection efficacy of vaccine candidate viruses against different strains of influenza virus in vivo. The results achieved from this project will advance our understanding of influenza vaccine development and facilitate the development of universal influenza vaccine.",,2021,University Of California Los Angeles,195000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +P23000,5U19AI135972-03,Project 1 - Host-virus networks regulating flu replication and host responses in vivo,"Influenza A virus is a major human respiratory pathogen, and available vaccines and antivirals are of limited efficacy. In order to identify novel targets for therapeutic intervention during influenza virus infection, we have assembled an interdisciplinary team that uses a highly integrated systems level approach to identify and validate key genes/networks involved in virus pathogenesis. The overarching theme of our multidisciplinary proposal “FluOMICS: The NEXT Generation” is to obtain multiple OMICS-based systems level measurements and integrate them using modeling approaches and machine learning algorithms to identify and validate 1) host-virus networks that modulate influenza A virus disease severity, 2) biomarkers in blood that reflect the activation states of these networks and 3) novel host targets for therapeutic interventions. The proposed studies leverage on our previous collaborations that generated global datasets and models that predict severity of disease caused by three specific influenza virus strains with different levels of pathogenicity. Our underlying main hypothesis is that host networks involved in viral replication and in early host responses regulate disease outcomes and represent promising targets for therapeutic intervention. We also propose that, in addition to the pathways identified in our previous collaboration, there are additional distinct pathways that result in either resilience or pathogenic outcomes after influenza virus infection, and that specific pathogenic pathways will require tailored therapeutic interventions. To identify networks associated with clinical disease in humans, we propose to integrate into predictive and comprehensive models OMICS responses during influenza virus infection in three systems 1) human blood from a human cohort of patients with documented influenza virus infection and diverse clinical outcomes (Project 1, Aim 3); 2) mouse blood and tissues from experimentally infected animals under a variety of conditions and perturbations resulting in diverse disease outcomes (Project 1, Aim 1) and 3) relevant primary human cells experimentally infected under controlled conditions and perturbations associated with diverse disease outcomes (Project 2). Samples will be collected, processed and send to the Technology Core to conduct global transcriptomics, proteomics and metabolomics analysis. OMICS data sets will be integrated and compared by the Modeling Core to generate network models of disease, uncover blood biomarkers and identify key drivers as targets for mechanistic studies and therapeutic intervention (Project 1, Aim 2). In summary, our systems modeling approaches will find correlates and associations between diverse experimental systems that will help us define human blood biomarkers, and link them to in vivo and ex vivo signatures for both companion diagnostics and personalized therapies.",,-99,ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI,499560,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity,2020 +P23001,3UM1AI148452-01S2,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2022,Vanderbilt University Medical Center,12509936,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P23002,1R41AI147902-01A1,Autonomous RNA-Mediated Anti-Influenza A Virus Therapeutics (AMRed Therapeutics),"Project Summary The NIAID has made one of its highest priorities the development of a universal influenza treatment. Current therapeutic strategies for timely neutralization of influenza A virus (IAV), the causative agent of both seasonal and pandemic flu, have been minimally effective. Moreover, seasonal flu vaccine strategies are typically less than 50% effective. Therefore, there continues to be an urgent need to generate both novel vaccine and therapeutic strategies against IAV to prevent and combat large scale outbreaks. We propose to advance our product, CM-BT1, through proof-of-concept mouse studies that will demonstrate rapid neutralization of IAV. CM-BT1 is a self-amplifying RNA replicon capable of driving host cell production of a protein, specifically a broadly neutralizing anti- HA stalk antibody. CM-BT1 is a member of our proprietary library of replicons, modified RNA dependent RNA polymerases (RdRp) derived from a diverse collection of plant and invertebrate viruses. CM-BT1, our lead product, stems from turnip crinkle virus (TCV) and has been demonstrated to successfully generate an RNA capable of self-replication and protein production in healthy mouse lungs in vivo. Importantly, we have also demonstrated safety in that CM-BT1 can be turned off when engineered with additional open reading frames and a self-targeting cassette that enables complete control of replicon activity without inducing any overt cytopathic effects to cells. The use of RNA as a therapeutic platform is an exciting new area of therapeutics made possible by recent advances in chemistry and synthetic biology. However, this potential therapeutic platform still remains somewhat limited in scope, owing largely to the short- lived nature of RNA. Our platform technology, and lead product, CM-BT1, overcomes these limitations through ongoing and controlled production of relevant gene products that can function for days, weeks, or possibly months. The purpose of this proposal is to demonstrate proof-of-concept in vivo using two lethal challenge IAV models. Using go/no-go criteria, CM-BT1 will be advanced through rigorous product development culminating in an efficacy study that will enable the launch of this product into full scale preclinical development for timely therapeutic neutralization of IAV.",,2022,"CELDARA MEDICAL, LLC",258360,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P23004,3UM1AI148452-01S1,Vanderbilt Vaccine and Treatment Evaluation Unit,"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research.",,2022,Vanderbilt University Medical Center,842642,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P23005,1R01AI146588-01A1,Biomimetic nanoparticles to enhance the breadth of influenza vaccines,"Abstract Current influenza (flu) vaccines are effective only for closely matched flu viral strains and must be updated annually to address constant antigenic shift/drifts of surface hemagglutinin (HA) and/or neuraminidase (NA) of the virus. Even with annual update, there have been years in which flu vaccines were ineffective due to significant differences in antigenicity of HA and/or NA between the strains used for preparing the vaccines and the circulating ones, leaving us at high risk of pandemics in case a new and highly pathological virus emerges. It is without any doubt that a “Universal” flu vaccine that can protect against both seasonal (matched or mismatched) and pandemic flu viruses is urgently needed, but it remains “an alchemist’s dream” so far. We developed a novel adjuvant by encapsulation of cGAMP, an agonist of the stimulator of interferon (IFN) gene (STING), into pulmonary surfactant (PS)-biomimetic liposomes (PS-GMNP). The adjuvant, alongside an inactivated flu vaccine, robustly stimulated humoral and CD8+ T cell immune responses that resemble those ocurring during the early phase of viral infection both in magnitude and in dynamics. Strikingly, a single dose of PS-GMNP-adjuvant flu vaccine elicited strong cross-protection against a lethal challenge of diverse heterosubtypic flu A viruses as early as 2 days after immunization. While stimulating robust heterosubtypic immunity, the adjuvant did not cause any adverse events in lung histology, body weight or temperature, in sharp contrast to the severe lung inflammation and death caused by flu viral infection. In this proposal, we will investigate the cellular and humoral immune responses essential to the cross-protection induced by PS- GMNP-adjuvanted flu vaccines. Specifically, we will determine whether PS-GMNP can expand cross-reactive CD8+ T cells and induce broadly neutralizing antibodies (bnAbs), pivotal to PS-GMNP-induced cross- protection. In Aim 2, we will preclude any adverse effects of pre-existing immunity on the adjuvanticity of PS- GMNP and extend the cross-protection to pre-pandemic wild type H5N1 and H7N9 viruses to establish its clinical potentials. Distinguished from conventional adjuvants that activate primarily antigen-presenting cells (APCs), cGAMP delivered by PS-GMNP activated both alveolar macrophages (aMɸ) and alveolar epithelial cells (AEC), which can be crucial since similar activation of these two types of cells is also observed during flu viral infection. Two alternative approaches will be employed in Aim 3 to corroborate indispensable function of AEC and/or aMɸ in PS-GMNP-mediated heterosubtypic immunity, including a blockade of cell-gap junctions and generation of chimeric mice of wild type and STING-deficient bone marrow (BM) cells. The study, if successful, could provide invaluable information about clinical potentials for PS-GMNP to widen the breadth of existing flu vaccines toward a “Universe” one, which will have a huge and immediate impact on global health.",,2024,MASSACHUSETTS GENERAL HOSPITAL,445294,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | H7,,,,H5N1,,H7N9,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2020 +P23006,1R43AI152652-01A1,Development of a Universal Influenza Vaccine,"ABSTRACT Influenza virus (flu) ranks highest in disease burden of all infectious diseases as measured in disability-adjusted life years. Seasonal epidemics cause 200,000-500,000 worldwide deaths annually. The total economic burden of seasonal flu is estimated to range from approximately $26B to $87B each year in the US in terms of direct medical expenses and lost work and productivity. Additionally, at least six known flu pandemics have become global human catastrophes, most notably the Spanish Flu pandemic of 1918, which killed 3-5% of the world’s population. Any reduction in the infection rate, transmission, and severity of flu infection would greatly reduce our healthcare expenditures and improve the quality of life for millions of people every year. The current vaccines are formulated annually based on predictions of which circulating flu strains may be prevalent in a given season. The effectiveness of these vaccines varies from year to year based on the circulation of unexpected antigenic variants and other factors. Vaccine design is complicated the by the multiplicity of flu strains, each with rapidly-evolving dominant antigen epitopes (“decoy” epitopes) that largely stimulate strain- restricted immunity. One strategy for rational antigen design, termed Immune Refocusing Technology (IRT), involves introducing mutations that reduce the immunogenicity of these decoy epitopes thus shifting the immune response to target more widely-conserved subdominant epitopes. BMI has previously applied this IRT approach with some notable successes to other viral antigens (e.g. HRV and the RSV F protein), and we now focus on the major flu surface antigen glycoprotein HA using H1, H3, and B vaccine strains as parental antigens. The anticipated effort to design a suitably modified antigen would ordinarily involve a protracted process of trial-and-error testing of many potential candidates. However, we have recently developed the ANATOPE automated B cell epitope prediction software package with algorithm parameters tuned using methods in artificial intelligence. Our algorithm identifies epitopes with a significantly higher success rate than previously available prediction programs. This breakthrough allows us to assign immunogenicity “strength” scores to particular antigen surface patches and will further guide and accelerate the design of mutant antigens that refocus the immune response to cross-strain conserved epitopes. In this application, we propose to engineer and test the immunogenicity of rationally-designed HA antigens containing mutations that both 1) dampen the immunogenicity of dominant strain-restricted decoy epitopes and 2) enhance the immunogenicity of conserved subdominant epitopes associated with broadly neutralizing antibodies. Follow- up studies will assess the rationally-designed antigens in a ferret challenge study and prepare the approach for translation into humans as a universal vaccine that does not require annual reformulation.",,2022,"BIOLOGICAL MIMETICS, INC.",299218,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3 | Other,Unspecified,,Unspecified,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P23007,3K23AI143967-02S1,Predictors of Influenza-Associated Absenteeism and Impact of Vaccination in a Cohort of Guatemalan Agricultural Workers,"PROJECT SUMMARY/ABSTRACT This is an application for a K23 Patient-Oriented Mentored Career Development award by Daniel Olson, MD. The proposed research will assess the clinical and socioeconomic impacts of influenza in a cohort of agricultural workers in Guatemala, evaluate clinical, biological, and socioeconomic predictors of influenza- associated absenteeism, and measure the effectiveness of workplace-based influenza vaccine in reducing disease and absenteeism. Candidate. Dr. Olson is a board-certified pediatrician and infectious disease (ID) specialist who is an Assistant Professor in the Department of Pediatrics at the University of Colorado (CU) School of Medicine, with a secondary appointment in the Department of Epidemiology in the Colorado School of Public Health. Training. Through hands-on mentored research, didactic coursework, and conferences/seminars, Dr. Olson’s K23 Career Development aims include: 1) Develop and formalize skills in clinical trial design and implementation, 2) Establish expertise in vaccinology, and 3) Obtain competencies to manage and develop a high quality global health research site. Mentors/Environment. Dr. Olson has assembled a diverse team of mentors, each with specific skills in his proposed research and career development aims. Dr. Edwin Asturias, an Associate Professor of Pediatric ID and Epidemiology at CU and the Jules Amer Chair of Community Pediatrics, will be his primary mentor. The remaining mentorship committee includes Dr. Lee Newman, Dr. Kathryn Edwards, Dr. May Chu, and Dr. Frederick Hayden, providing a diverse group of senior level mentors with broad experience and expertise. Research. Low- and middle-income countries (LMICs) continue to suffer a disproportionate burden of influenza disease. Workplace influenza vaccination programs may offer a cost-effective strategy to limit absenteeism and lost productivity due to influenza. Agricultural workers represent an economically strategic workforce in Latin America, and the drivers of illness-associated absenteeism, such as influenza, are unknown. The CU research site in Guatemala has an established cohort of 2,706 agricultural workers from a nearby banana plantation and a well-trained research team. To better understand the impact of influenza on agricultural workers and the drivers of work absenteeism, we aim to 1) Evaluate the clinical and socioeconomic impacts of influenza on a cohort of Guatemalan agricultural workers and determine predictors of work absenteeism due to influenza, and 2) Measure the effectiveness of influenza vaccination on disease incidence, absenteeism, and job performance in the same cohort. We hypothesize that influenza places a significant burden on agricultural workers, that specific clinical, biological, and socioeconomic predictors may be associated with greater absenteeism, and that a workplace-based influenza vaccine program will significantly reduce clinical disease and influenza-associated absenteeism.",,2022,University Of Colorado Denver,108783,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Epidemiological studies",Indirect health impacts | Economic impacts | Impact/ effectiveness of control measures,2020 +P23008,1R01AI154470-01,Immunobiology of Influenza Virus-related Critical Illness in Young Hosts,"ABSTRACT Influenza virus is a persistent global menace that every year infects an estimated 5-10% of adults and 20-30% of children worldwide causing over 500,000 influenza-related deaths. Most annual influenza infections are in the very young, the elderly, and in individuals with chronic health conditions such as asthma. However, recurrent influenza pandemics caused by the emergence and spread of highly pathogenic novel influenza A strains, such as occurred in 2009, disproportionately causes severe illness in healthy children and younger adults. This study of life-threatening influenza virus lower respiratory tract infection (LRTI) in young hosts is designed by an established multidisciplinary group of investigators to better understand how host innate and adaptive immunity to influenza virus is associated with disease susceptibility, severity and clinical outcomes. In the Pediatric Intensive Care Influenza (PICFLU1) study, we hypothesized that infection with the influenza virus triggers hypercytokinemia and immune dysregulation in a genetically susceptible host resulting in severe life-threatening infection. Confirming our hypothesis, in PICFLU1 (AI084011, enrolling 2008-2016), we identified a hyperinflammatory phenotype coexisting with innate immunosuppression; both were associated with mortality. We also identified associations between functional variants in IFITM3 and MBL2 with pediatric influenza-related death. In the Immunobiology of Influenza Virus-Related Critical Illness in Young Hosts study (PICFLU2, enrolling 2020-2025), we test the hypothesis that distinct severe influenza LRTI phenotypes â€Â"" defined by host immunobiology â€Â"" can be identified for targeted preventive and therapeutic interventions. In this study we aim to: 1. Identify biomarkers in children with severe influenza LRTI that can be used for prognostic stratification and predictive enrichment in future immunomodulatory clinical trials; 2. Determine if pre-existing strain specific immunity to influenza virus protects against life-threatening disease and influences viral shedding and disease severity; and 3. Identify genes essential for anti-viral immunity and/or containment that explain host susceptibility to severe influenza infection or its outcome. To achieve these aims, we will enroll 600 additional children and young adults with confirmed influenza infection (300 intensive care unit and 300 ward or outpatient) across 35 PICFLU sites. Across PICFLU studies (2008-2025) we will have DNA on ~1,000 young hosts infected with influenza virus to identify important endophenotypes for risk stratification and predictive enrichment in future clinical trials targeting prevention of and more rapid recovery from severe influenza-related disease. Identified influenza virus susceptibility and severity genes are potential “druggable targets” for immune modulation. Our findings could personalize the care of young individuals with severe influenza infection based on distinct immunobiologic host phenotypes based on patient age, influenza strain, clinical presentation, innate and adaptive immune biomarkers and host genetics.",,2024,BOSTON CHILDREN'S HOSPITAL,1267324,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2020 +P23009,5F31AI164939-03,Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence,"Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence Aedes aegypti, is the primary vector of emerging arboviruses causing serious human illnesses including yellow fever, dengue, Zika, and chikungunya. Species population dynamics are related to urbanization and human density as larvae develop in man-made habitats and bloodfeed on humans. Previous studies have independently related urbanization parameters, detrital inputs, and larval competition to some aspects of Ae. aegypti life history (e.g., development time, biomass, fecundity) and vector competence. However, no study has determined how urbanization can influence these ecological interactions in larval habitats, the effect that this can have on Ae. aegypti performance across life stages, generations, and vector competence, nor have used a nutrient stoichiometry approach to do so. Urbanization changes could translate to changes in detritus availability and species competition in larval habitats along a gradient of urbanization which could in turn, influence the susceptibility of Ae. aegypti to dengue infection. The first objective of this proposal is to determine the influence of urbanization on Ae. aegypti larval bottom-up effects and competition in Puerto Rico. The second and third objectives are to assess the influence of urbanization related-detrital inputs and Aedes sp. competition on the species life history across generations and vector competence, respectively. Preliminary data suggests that plant detritus biomass and composition have a significant effect on Ae. aegypti larval and adult biomass. In addition, container water nitrogen (%N) significantly increases with urbanization, that water Carbon:Nitrogen (C:N) is significantly higher in suburban containers, and C:N exhibits a significant relationship with Ae. aegypti larval biomass. The overall hypothesis of this proposal is that urbanization influences detrital inputs and competition in Ae. aegypti larval habitats and that this variation will affect species performance (survival, development rate, and biomass) and dengue vector competence. A combination of field sampling and laboratory experiments will be used to answer the objectives. Sixty larval containers will be sampled across a gradient of urbanization in San Juan, Puerto Rico following a stratified random sampling method with three strata (urban density): low, medium, and high. Incubated containers will simulate larval conditions of each strata with combinations of detrital inputs and species intraspecific and interspecific competition. Aedes aegypti females will be infected with a dengue blood meal to determine virus dissemination and transmission rates. Nutrient analysis (i.e., %C %N, C:N) will be performed on container water, detritus, larvae, and adults from field and laboratory experiments. The results of this research have relevance to vector ecology, vector control strategies, arbovirus diseases, and public health.",,2025,UNIVERSITY OF SOUTHERN MISSISSIPPI,35951,Human Populations | Disease Vectors,Unspecified | Not applicable,Adults (18 and older) | Not Applicable,Urban Population/Setting,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P23010,5R21AI174516-02,A Cell-specific modified CRISPR/Cas9 system for conditional gene disruption in Aedes aegypti,"PROJECT SUMMARY/ABSTRACT Mosquito-borne disease is a major source of human misery, sickening hundreds of millions and killing hundreds of thousands of people annually. The yellow fever mosquito Aedes aegypti is a primary vector for the viruses that cause dengue, Zika and chikungunya and other diseases. In addition to its medical importance, Ae. aegypti is increasingly used for molecular genetic studies of mosquito vector biology. Understanding Ae. aegypti biology will provide basic science insights into this mosquito vector’s development, physiology and behavior, help inform implementation of control efforts and potentially suggest new control strategies. Improving approaches for genetic investigations in Ae. aegypti will facilitate these efforts. To date, genetic investigations in Ae. aegypti often rely on CRISPR/Cas9-mediated gene targeting to create strains of homozygous mutant animals in which a gene of interest has been disrupted. While extremely valuable, substantial effort is required to create each mutant and the mutants obtained lack cell-specificity. To address these limitations, we propose to establish a cell-specific, modified CRISPR/Cas9 (CmC) toolkit for Ae. aegypti. CmC is designed to decrease the effort required to examine the impact of disrupting a gene of interest, allow the cells in which a gene is acting to be determined and aid the study of essential genes. We propose to achieve these goals in two aims: Aim #1: Introduce the tools for Cell-specific modified CRISPR/Cas9 (CmC) into Ae. aegypti In aim 1a, we design a strategy and build tools for creating mosquito strains that express modified Cas9 transgenes designed to allow optimization of Cas9 levels. In aim 1a2, we use these tools to create mosquitoes that express modified Cas9 transgenes in a specific subset of sensory neurons. In aim 1b, we create transgenes that express multiple gRNAs in a cell-specific fashion to specify the genes targeted. Aim 2: Implement CmC in a subset of sensory neurons as well as pan-neuronally In aim 2a, we test the system, using the tools built to identify an optimal strain which promotes robust cell- specific gene disruption in a subset of sensory neurons, without causing cell death. In aim 2b, we construct mosquito strains that will enable broad neuron-specific gene disruption, which should be of wide utility.",,2024,BRANDEIS UNIVERSITY,182813,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2022 +P23012,5R01AI171032-02,Juvenile hormone transporters in disease vector physiology,"PROJECT SUMMARY/ABSTRACT Development and reproduction of insects, including human disease vectors such as mosquitoes, are mainly controlled by two lipophilic hormones: ecdysone and juvenile hormone (JH). Although these hormones need to enter their target cells to exert their biological effects, almost nothing is known regarding molecular mechanisms that regulate hormone transport across cellular membranes. This is due to the prevailing dogma in endocrinology that lipophilic hormones enter and exit cells by simple diffusion across lipid bilayers. However, despite this dominant assumption, the simple diffusion model of lipophilic hormone transport is not supported by any conclusive evidence in any organism. Indeed, recent studies now suggest that some lipophilic hormones, including the insect steroid hormone ecdysone, require membrane transporter proteins to travel across plasma membranes. The overall objective of this project is to identify and characterize membrane transporters required for JH trafficking across cellular membranes, and to thereby challenge the conventional paradigm that lipophilic hormones freely enter and exit cells by simple diffusion. The approach will combine in vitro and in vivo approaches to characterize JH Transporter (JHT), which was discovered in preliminary studies using the fruit fly model system. In Aim 1, functions of the JHT ortholog in the yellow fever mosquito Aedes aegypti, the primary vector for Zika, yellow fever, chikungunya, and dengue viruses, will be thoroughly investigated in vitro using an arsenal of molecular genetic tools. In Aim 2, JHT functions will be further studied genetically in Aedes. As JH controls both growth and reproduction in Aedes and other mosquitoes, characterization of Aedes JHT is expected to aid our effort to combat these deadliest disease vectors for humans. Indeed, in Aim 3, in vitro chemical screening will be conducted to identify compounds that can inhibit functions of Aedes JHT, and their effects will be tested in vivo. The significance of this project is therefore not just to overturn the long-standing dogma in endocrinology, but also to provide a critical proof of concept as well as seed compounds for developing novel pharmacological tools to control mosquitoes and other deadly disease vector insects.",,2027,UNIVERSITY OF CALIFORNIA RIVERSIDE,341489,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P23013,5R21AI176101-02,Molecular and cellular basis of mosquito olfactory attraction to hay infusion for enhanced vector surveillance and control,"The mosquito Aedes aegypti is a prolific disease vector that thrives in urban environments. Its explosive population dynamics are driven by the ability of female Ae. aegypti to seek out standing pools of water to lay their desiccation-resistant eggs. Of note, females are attracted to the scent of decomposing botanical matter in water, but only after mating and blood-feeding. In particular, gravid female Ae. aegypti are highly attracted to the scent of fermenting African Bermuda grass hay in water, which has been exploited for mosquito trapping strategies in the field that aim to lure this major disease vector to its death during the act of egg laying. We propose to apply integrative methods to define the molecular and cellular basis of Ae. aegypti olfactory attraction to hay infusion which will catalyze identification of olfactory circuitry mediating oviposition site search and novel oviposition attractants for this disease vector. To elucidate candidate chemoreceptors and associated neurons implicated in mosquito olfactory attraction to hay infusion, we will test the role of different chemoreceptor classes using loss-of-function genetics and olfactory sensory neuron populations by selectively disrupting neural activity using cell-type specific neuronal silencing. In parallel, we aim to reverse engineer attractive blends of oviposition attractants mimicking the scent of hay infusion by leveraging chemical analysis of infusion headspace combined with neural activity assays that compare olfactory sensitivity and response amplitudes of non-gravid and gravid mosquitoes to conserved volatile organic compounds found in this this natural lure. These aims will fundamentally improve our understanding of the chemosensory basis of Ae. aegypti oviposition site search behavior. From a translational perspective, this research will reveal new molecular targets in the Ae. aegypti olfactory system to modulate mosquito egg laying behavior and identify novel synthetic formulations of oviposition attractants for enhanced population surveillance and control of this globally important disease vector.",,2024,JOHNS HOPKINS UNIVERSITY,184219,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P23018,5F31AI164939-02,Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence,"Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence Aedes aegypti, is the primary vector of emerging arboviruses causing serious human illnesses including yellow fever, dengue, Zika, and chikungunya. Species population dynamics are related to urbanization and human density as larvae develop in man-made habitats and bloodfeed on humans. Previous studies have independently related urbanization parameters, detrital inputs, and larval competition to some aspects of Ae. aegypti life history (e.g., development time, biomass, fecundity) and vector competence. However, no study has determined how urbanization can influence these ecological interactions in larval habitats, the effect that this can have on Ae. aegypti performance across life stages, generations, and vector competence, nor have used a nutrient stoichiometry approach to do so. Urbanization changes could translate to changes in detritus availability and species competition in larval habitats along a gradient of urbanization which could in turn, influence the susceptibility of Ae. aegypti to dengue infection. The first objective of this proposal is to determine the influence of urbanization on Ae. aegypti larval bottom-up effects and competition in Puerto Rico. The second and third objectives are to assess the influence of urbanization related-detrital inputs and Aedes sp. competition on the species life history across generations and vector competence, respectively. Preliminary data suggests that plant detritus biomass and composition have a significant effect on Ae. aegypti larval and adult biomass. In addition, container water nitrogen (%N) significantly increases with urbanization, that water Carbon:Nitrogen (C:N) is significantly higher in suburban containers, and C:N exhibits a significant relationship with Ae. aegypti larval biomass. The overall hypothesis of this proposal is that urbanization influences detrital inputs and competition in Ae. aegypti larval habitats and that this variation will affect species performance (survival, development rate, and biomass) and dengue vector competence. A combination of field sampling and laboratory experiments will be used to answer the objectives. Sixty larval containers will be sampled across a gradient of urbanization in San Juan, Puerto Rico following a stratified random sampling method with three strata (urban density): low, medium, and high. Incubated containers will simulate larval conditions of each strata with combinations of detrital inputs and species intraspecific and interspecific competition. Aedes aegypti females will be infected with a dengue blood meal to determine virus dissemination and transmission rates. Nutrient analysis (i.e., %C %N, C:N) will be performed on container water, detritus, larvae, and adults from field and laboratory experiments. The results of this research have relevance to vector ecology, vector control strategies, arbovirus diseases, and public health.",,2025,UNIVERSITY OF SOUTHERN MISSISSIPPI,35951,Human Populations | Disease Vectors,Unspecified | Not applicable,Adults (18 and older) | Not Applicable,Urban Population/Setting,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P23019,1R21AI174516-01,A Cell-specific modified CRISPR/Cas9 system for conditional gene disruption in Aedes aegypti,"PROJECT SUMMARY/ABSTRACT Mosquito-borne disease is a major source of human misery, sickening hundreds of millions and killing hundreds of thousands of people annually. The yellow fever mosquito Aedes aegypti is a primary vector for the viruses that cause dengue, Zika and chikungunya and other diseases. In addition to its medical importance, Ae. aegypti is increasingly used for molecular genetic studies of mosquito vector biology. Understanding Ae. aegypti biology will provide basic science insights into this mosquito vector’s development, physiology and behavior, help inform implementation of control efforts and potentially suggest new control strategies. Improving approaches for genetic investigations in Ae. aegypti will facilitate these efforts. To date, genetic investigations in Ae. aegypti often rely on CRISPR/Cas9-mediated gene targeting to create strains of homozygous mutant animals in which a gene of interest has been disrupted. While extremely valuable, substantial effort is required to create each mutant and the mutants obtained lack cell-specificity. To address these limitations, we propose to establish a cell-specific, modified CRISPR/Cas9 (CmC) toolkit for Ae. aegypti. CmC is designed to decrease the effort required to examine the impact of disrupting a gene of interest, allow the cells in which a gene is acting to be determined and aid the study of essential genes. We propose to achieve these goals in two aims: Aim #1: Introduce the tools for Cell-specific modified CRISPR/Cas9 (CmC) into Ae. aegypti In aim 1a, we design a strategy and build tools for creating mosquito strains that express modified Cas9 transgenes designed to allow optimization of Cas9 levels. In aim 1a2, we use these tools to create mosquitoes that express modified Cas9 transgenes in a specific subset of sensory neurons. In aim 1b, we create transgenes that express multiple gRNAs in a cell-specific fashion to specify the genes targeted. Aim 2: Implement CmC in a subset of sensory neurons as well as pan-neuronally In aim 2a, we test the system, using the tools built to identify an optimal strain which promotes robust cell- specific gene disruption in a subset of sensory neurons, without causing cell death. In aim 2b, we construct mosquito strains that will enable broad neuron-specific gene disruption, which should be of wide utility.",,2024,BRANDEIS UNIVERSITY,243750,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2022 +P23021,1R43AI170123-01A1,An Isothermal Method to Amplify RNA from Bloodborne Viruses,"PROJECT SUMMARY Bloodborne RNA viruses, in particular HIV-1 and hepatitis C, are a major public health burden. The diagnostic gold standard for these viruses is the use of RT-qPCR, which is expensive for use in developing countries. Traditional tests for HIV-1 also cannot be used to assess antiretroviral efficacy, as RT-qPCR could pick up integrated DNA and serological tests can detect antigens chromosomally expressed from integrated DNA. We propose the development of a diagnostic assay that will amplify and detect the RNA of bloodborne RNA viruses via a unique RNA amplification process. By developing a method to enrich viral RNAs over eukaryotic or bacterial RNAs we can lower the limit of detection and potentially reduce the level of false positives and negatives observed when using RT-based diagnostics. As this method is specific for viral RNA in general, it can be used for other human ssRNA viral pathogens, such as Zika or Dengue. The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of a new step in viral RNA detection, usable for detecting the five bloodborne viruses we propose here, but also other ssRNA viruses. By using an isothermal approach to amplify viral RNA our device will eliminate the need for expensive equipment, which will increase access to testing. In the wake of the SARS-CoV-2 pandemic, the general public learned that Point-of-Care (POC) tests for antibodies or antigens do not detect low levels of viral infections. We propose to develop a test that will selectively amplify viral RNAs, which will bring the sensitivity of nucleic acid amplification to POC providers. The proposed work will validate the specificity of the enzyme toward viral RNAs, develop a system to extract and detect these RNAs, and lower the detection limit for POC diagnostics.",,2024,"LYNNTECH, INC.",290196,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae | Other | Unspecified,,,,,,,,,COVID-19 | Zika virus disease | Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2023 +P23022,5R01DC018403-04,The taste of ribonucleosides: The molecular and cellular basis underlying chemosensory detection of previously unknown macronutrients,"Insects are the most abundant class of animals, next to vertebrates. For example, the biomass of termites alone equals that of humans, the most abundant mammal. There are about 1 million named insect species and approximately another 5 million yet to be classified, compared to about 66,000 species of vertebrates. While overall beneficial to our ecosystem, some insects have considerable negative impact on human health. Disease vectors, mostly flies and mosquitoes, are major transmitter of microbes that cause devasting human diseases, including yellow fever, dengue, malaria and zika. These insect vectors kill close to a million people each year, sicken hundreds of millions more and incur billions of dollars annually in costs for treatment and lost productivity. Other insect species are agricultural pests and consume crops and fruits of cultivated plants, leading to famine in many parts of the world. In light of these facts, a better understanding of insect biology and behavior, in particular chemosensory behavior, is paramount for developing specific and effective strategies for population control of harmful pests. Drosophila melanogaster, with its array of experimental tools, is uniquely suited to uncover the basic principles underlying these behaviors. Like mammals and other insects, Drosophila depend on chemosensory systems to navigate their external world appropriately. The sense of taste is particularly important to identify food sources and avoid harmful chemicals. To assure that all essential food chemicals are consumed, insects have evolved appetitive taste receptors for the three major macronutrients, proteins, carbohydrates and fats. Intriguingly, Drosophila larvae, in contrast to adult flies, can also sense ribonucleosides and RNA in their food. These chemicals represent an essential resource required to support rapid growth and survival during the fast-growing larval stages. Larvae employ a small number of closely related taste receptors, the Gustatory Receptors (Grs) 28 to detect these chemicals. The Gr28 genes are among the most conserved insect taste receptor genes, homologs of which are found in all insect genomes, from flour beetles to honeybees to mosquitoes. These observations suggest that the Gr28 genes have a conserved role, namely to detect RNA and ribonucleosides in insects. Remarkably, some of the Gr28 genes have been implicated in temperature and light sensing, expanding their role to sensory pathways beyond taste. Thus, an in-depth understanding of the function of receptors for RNA and ribonucleosides is of considerable interest, especially because they are broadly conserved in diverse insect species, from disease vectors (mosquitoes and flies), to agricultural pests (beetles, grasshoppers) and ecologically beneficial pollinators (honeybees). Exploiting the ability of insects to sense RNA and ribonucleosides via specific taste receptors may provide new opportunities to develop strategies for control of harmful insects.",,2025,TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR,376597,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P23023,5UC2GM141586-03,Developing a Culture of Biomedical Research at the University of the Virgin Islands,"PROJECT SUMMARY This proposal will enhance and innovate the biomedical research infrastructure and training at the University of the Virgin Islands (UVI), the only higher educational institution in the US Virgin Islands (USVI). The overall objective of this proposal is to provide the highest level of sponsored program services for biomedical research by developing a culture of research through training, mentoring, collaboration and a strong infrastructure. UVI’s vision is to develop research resulting in an increase in the number of faculty conducting excellent externally funded biomedical research who will be able to mentor undergraduate students with potential for careers in science. There are several motivating factors for this project: (1) Diversity in the scientific workforce is key to the future biomedical discoveries that will improve the health of the Nation, and HBCUs such as UVI have an important role to play in training students who are underrepresented in science. (2) The USVI is a medically underserved area that experiences dramatic health disparities and emerging diseases including dengue, chikungunya, Zika, and the more recent coronavirus, which are important not only in the Caribbean but are also increasing on the US mainland. Little research on population health has been performed in the USVI and UVI continues to look at research in these areas. (3) Extensive undergraduate research experience is essential to prepare students for highly competitive doctoral programs. Although UVI has very successful programs that mentor undergraduates in research, there are many more UVI students interested in research experience than can be accommodated in externally funded research laboratories. (4) UVI has established a culture of innovation in its 2018-2023 Strategic Plan and through this research infrastructure and innovation is a primary focus area and is supported by the President and senior leadership. The UVI Institutional Development Plan (IDP) addresses barriers to research and informs the Specific Aims of this proposal: (1) Develop UVI’s research administration leadership and organization such that it is well-trained, resourced, and motivated to support a culture of research. (2) Develop research review and training programs for research faculty to increase the number and improve the competitiveness of proposal submissions (3) Increase mentorship and training opportunities for undergraduates in biomedical research by supporting faculty to receive external funding. This program is innovative because it will fully integrate the IDP for research within UVI’s 2018-2023 Strategic Plan, providing strong institution-wide commitment. Research and training innovations include targeted training initiatives covering the life cycle of research, increased outreach efforts, training and grant writing initiatives and focus groups of HBCU research administrators to overcome the barrier of geographic isolation. UVI’s logic model will be used to ensure that each activity will contribute to a sustainable vision for research and to developing a University-wide culture supporting research.",,2025,UNIVERSITY OF THE VIRGIN ISLANDS,292003,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research on Capacity Strengthening,Individual level capacity strengthening | Institutional level capacity strengthening,2021 +P23024,1R01AI171032-01A1,Juvenile hormone transporters in disease vector physiology,"PROJECT SUMMARY/ABSTRACT Development and reproduction of insects, including human disease vectors such as mosquitoes, are mainly controlled by two lipophilic hormones: ecdysone and juvenile hormone (JH). Although these hormones need to enter their target cells to exert their biological effects, almost nothing is known regarding molecular mechanisms that regulate hormone transport across cellular membranes. This is due to the prevailing dogma in endocrinology that lipophilic hormones enter and exit cells by simple diffusion across lipid bilayers. However, despite this dominant assumption, the simple diffusion model of lipophilic hormone transport is not supported by any conclusive evidence in any organism. Indeed, recent studies now suggest that some lipophilic hormones, including the insect steroid hormone ecdysone, require membrane transporter proteins to travel across plasma membranes. The overall objective of this project is to identify and characterize membrane transporters required for JH trafficking across cellular membranes, and to thereby challenge the conventional paradigm that lipophilic hormones freely enter and exit cells by simple diffusion. The approach will combine in vitro and in vivo approaches to characterize JH Transporter (JHT), which was discovered in preliminary studies using the fruit fly model system. In Aim 1, functions of the JHT ortholog in the yellow fever mosquito Aedes aegypti, the primary vector for Zika, yellow fever, chikungunya, and dengue viruses, will be thoroughly investigated in vitro using an arsenal of molecular genetic tools. In Aim 2, JHT functions will be further studied genetically in Aedes. As JH controls both growth and reproduction in Aedes and other mosquitoes, characterization of Aedes JHT is expected to aid our effort to combat these deadliest disease vectors for humans. Indeed, in Aim 3, in vitro chemical screening will be conducted to identify compounds that can inhibit functions of Aedes JHT, and their effects will be tested in vivo. The significance of this project is therefore not just to overturn the long-standing dogma in endocrinology, but also to provide a critical proof of concept as well as seed compounds for developing novel pharmacological tools to control mosquitoes and other deadly disease vector insects.",,2027,UNIVERSITY OF CALIFORNIA RIVERSIDE,379641,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P23026,5R01AI167300-03,Sublingual Supramolecular Vaccines and Immunotherapies,"Even when vaccines are rapidly developed and shown to be efficacious and safe, vaccination campaigns continue to be hampered by public hesitancy and by challenges distributing vaccines equitably around the globe. Vaccine hesitancy, where individuals refuse or delay vaccination, has been a persistent challenge, affecting a third to a quarter of individuals in the US and globally. Inequitably, it affects racial and ethnic minority communities particularly strongly, and in 2019 the World Health Organization named vaccine hesitancy as one of the top-ten threats to global health. Needle-based injections, which increase vaccine reactogenicity, are a significant driver of vaccine hesitancy. A second fundamental hurdle in equitable availability of vaccines involves the chain of distribution. Most vaccines must be transported and stored within a continuous cold-chain to prevent loss of potency, making global distribution challenging. In the face of these limitations, lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking vaccines, yet the issues of global distribution and patient acceptance are exponentially more challenging with repeated dosing. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered specifically for the sublingual route to provide for effective vaccination. The project aims to design a shelf- stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of- concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of immune responses remain to be articulated. Therefore the objective of the project is to articulate these design rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size, charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza, zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).",,2026,DUKE UNIVERSITY,437499,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Orthomyxoviridae,Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2021 +P23027,5R01AI165575-03,Opsins and TRP channels controlling sensation and behavior in Aedes aeygpti,"Abstract The mosquito Aedes aegypti spreads diseases such as dengue, Zika, yellow fever, and others that afflict >100 million people each year. These mosquitoes rely on multiple keen senses to locate human hosts for blood meals, and for finding conspecifics for mating. Currently, we have only a rudimentary understanding of the receptors that control these critical behaviors. The goal of the proposed research is to address this gap. The unifying theme of this proposal is to test the idea that opsins and TRP channels are two key classes of signaling proteins that have broad roles in sensation and in controlling behavior in Ae. aegypti. Rhodopsins are the founding G-protein coupled receptors (GPCRs). We recently discovered that opsins are multi-modal sensory receptors, challenging 100 years of dogma that they detect only light. To find humans, female Ae. aegypti integrate information from diverse stimuli, including CO2, visual cues, organic molecules, and convection heat from skin. We discovered another cue. Aim 1 builds on our preliminary data that Ae. aegypti use infrared (IR) radiation as an additional host stimulus. We outline experiments to reveal the roles of opsins and the TRPA1 channel in IR detection. We propose to identify the IR-sensing neurons that express the opsins and TRPA1, and to test a model to explain the role of opsins in IR sensation. To pursue this aim, we devised a highly effective assay for monitoring IR attraction and a new molecular genetic approach to bypass difficulties in combining multiple genetic elements. Aim 2 takes advantage of a mutation that we created in another TRP (TRPV-A), which renders males and females deaf. We will test the roles of hearing and TRPV-A in swarm formation, in mating, and in finding humans. Aim 2 will also build on the observations that male mating requires audition mediated by TRPV-A to devise a strategy to overcome a major impediment limiting the efficacy of the sterile insect technique (SIT). SIT is a promising strategy to suppress Ae. aegypti. It involves inundating a local population with sterile males, which then render females sterile upon mating. An obstacle to using SIT is that wild-type males outcompete sterile males. We propose that manipulation of the activity of the TRPV-A- expressing auditory neurons elevates sterile male mating success, and will thereby increase the efficacy of SIT in suppressing Ae. aegypti. Aim 3 concerns identifying the sensory receptors for repellents. We propose to test the idea that an opsin functions as a highly sensitive receptor for insect repellents. If confirmed by the proposed experiments, this would demonstrate that opsins comprise a new class of olfactory receptor. To accomplish our goals, we have developed an extensive repertoire of state-of-the-art approaches. These include new molecular genetic tools, a suite of behavioral assays, original video tracking software, and in vivo electrophysiological recordings. In summary, this project will reveal the roles of opsins and TRP channels in allowing mosquitoes to sense humans and conspecific mates. The insights gleaned from this work have exciting potential to lead to innovative strategies to control Ae. aegypti and reduce insect-borne disease.",,2026,UNIVERSITY OF CALIFORNIA SANTA BARBARA,542566,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2021 +P23030,5U01DP006583-03,RFA-DP-21-001 Georgia Pregnancy Risk Assessment Monitoring System (PRAMS) Project,"Project Summary The Georgia Pregnancy Risk Assessment Monitoring System (PRAMS) Project is a statewide, ongoing population‐based survey that collects information on women with a recent live birth in Georgia. Georgia PRAMS initiated sampling with January 1993 births. PRAMS survey data complements Vital Records data by collecting information about mothers’ attitudes, behaviors, and experiences before, during, and shortly after pregnancy. Survey topics include preconception health, pregnancy intention, prenatal care, health insurance, oral health during pregnancy, substance use, breastfeeding, safe sleep behaviors and environment, intimate partner violence, maternal stressors, contraception use and methods, and supplemental topics as emergent public health issues arise (ex: Zika Virus, Coronavirus Disease 2019), among others. Each month, a stratified random sample of approximately 110 women is drawn from birth certificate records accessed through the State Office of Vital Records. The current stratification variable is preterm birth (gestational age greater than 20 and less than 37 weeks versus all other births). The stratification scheme can vary by year and is used to ensure adequate representation of key subgroups in the sample. Sampled PRAMS participants are surveyed two to six months after delivery of their infant first by mail and then by phone if a mail survey response is not received. Each mother’s survey is linked to her infant’s birth certificate. The goal of the Georgia PRAMS Project is to provide population-based data on maternal experiences and behaviors before, during, and after pregnancy and during early infancy which can be used to reduce the risk of adverse birth outcomes and improve the health of mothers and infants in Georgia. Georgia PRAMS is the only data source for many key indicators of maternal and child health in the state, providing essential data to identify disparities, select maternal and child health priorities, inform and evaluate programs, and inform policy changes to improve the health of all mothers and infants in Georgia.",,2026,GEORGIA STATE DEPARTMENTOF PUBLIC HEALTH,174998,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P23031,1R21AI176101-01,Molecular and cellular basis of mosquito olfactory attraction to hay infusion for enhanced vector surveillance and control,"The mosquito Aedes aegypti is a prolific disease vector that thrives in urban environments. Its explosive population dynamics are driven by the ability of female Ae. aegypti to seek out standing pools of water to lay their desiccation-resistant eggs. Of note, females are attracted to the scent of decomposing botanical matter in water, but only after mating and blood-feeding. In particular, gravid female Ae. aegypti are highly attracted to the scent of fermenting African Bermuda grass hay in water, which has been exploited for mosquito trapping strategies in the field that aim to lure this major disease vector to its death during the act of egg laying. We propose to apply integrative methods to define the molecular and cellular basis of Ae. aegypti olfactory attraction to hay infusion which will catalyze identification of olfactory circuitry mediating oviposition site search and novel oviposition attractants for this disease vector. To elucidate candidate chemoreceptors and associated neurons implicated in mosquito olfactory attraction to hay infusion, we will test the role of different chemoreceptor classes using loss-of-function genetics and olfactory sensory neuron populations by selectively disrupting neural activity using cell-type specific neuronal silencing. In parallel, we aim to reverse engineer attractive blends of oviposition attractants mimicking the scent of hay infusion by leveraging chemical analysis of infusion headspace combined with neural activity assays that compare olfactory sensitivity and response amplitudes of non-gravid and gravid mosquitoes to conserved volatile organic compounds found in this this natural lure. These aims will fundamentally improve our understanding of the chemosensory basis of Ae. aegypti oviposition site search behavior. From a translational perspective, this research will reveal new molecular targets in the Ae. aegypti olfactory system to modulate mosquito egg laying behavior and identify novel synthetic formulations of oviposition attractants for enhanced population surveillance and control of this globally important disease vector.",,2024,JOHNS HOPKINS UNIVERSITY,241163,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P23032,3U01AI151378-04S2,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,359092,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23033,3D43TW010919-06S1,Exploration of Cloud Solutions to Enhance Global Infectious Diseases Research Training Program Activities,"Jamaica and the Caribbean region endure cyclic epidemics of arboviral diseases transmitted by Aedes mosquitoes, including chikungunya, dengue, yellow fever, and Zika. Ministries of Health (MOH) across the region constantly monitor the spread of these viruses and conduct routine surveillance for the emergence of pandemic strains of respiratory viruses including influenza and SARS-CoV-2. The University of the West Indies (UWI) in Jamaica plays a key role in viral surveillance as it houses the National Influenza Center which provides weekly reports to the Surveillance Unit of the MOH. In addition, it has Jamaica's only Next Generation Sequencer which is used in both surveillance and research. This supplement application will support and expand the objectives of the parent grant, Global Infectious Diseases (GID) Research Training Progrsn The GID recently received a competitive renewal to train the next generation of Jamaican researchers using cutting edge methodologies. We consider that working knowledge of data migration and manipulation in a shared computational cloud environment is essential. The goal of this supplement application is to migrate virus surveillance data to the cloud to allow for deeper analysis by researchers and trainees from multiple UWI campuses and access to richer data for new research projects. The first phase will allow collaborators at University at BuffalolSUNY, UWI, and CTIS, Inc., the cloud collaborator, to meet virtually for training purposes and determine the most efficient strategy for migration of existing virus surveillance databases maintained at UWI and the MOH to the cloud. The MOH operates five surveillance sites across Jamaica from which samples from individuals with fever, rash and respiratory illness are submitted to the UWI Department of Microbiology or the National Public Health Laboratory for diagnosis. The Surveillance Unit produces a weekly epidemiological bulletin which is shared on its website, but the data are not readily available for further analysis and no additional research occurs. Data from this database are shared with the Pan American Health Organization and Caribbean Public Health Agency to publish bulletins on viral incidence. The second phase will include migration of the data, initial testing and review among the MOH-GID team, before the cloud dataset is made ""live."" The third phase will assess how the cloud resource was used by the MOH-GID team and the broader research community, and costs and benefits. The UWI is at the forefront of virology research and training through its graduate research programs in viral discovery in human and mosquito vectors through a collaborative network of investigators. These programs will gain from the proposed exploration of cloud solutions to enhance infectious diseases research in Jamaica.",,2024,STATE UNIVERSITY OF NEW YORK AT BUFFALO,163791,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2023 +P23034,5U01CK000580-04,PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ARBOVIRUSES (PRESCA) PROGRAM,"PROJECT SUMMARY The impact of infections transmitted by mosquitoes is global. Arboviral diseases such as dengue, chikungunya, and Zika are a significant health concern due to the expanding geographical range of many mosquito species. Emphasis on disease surveillance systems is central to evaluate the effectiveness of primary and secondary dengue prevention methods and strategies, including the introduction of dengue vaccines and new vector control methods. In the current application, the study team will address specific and fundamental gaps in the diagnosis and clinical management of dengue and other acute febrile illnesses (AFI); ultimately, evaluating the efficacy of vector control strategies in reducing the incidence of arbovirus infection through a combination of both clinic- and community-based surveillance systems. The study team’s long-term goal is to mitigate arboviral and other AFI disease burdens by improving diagnosis, clinical management, and prevention strategies. The study’s central hypothesis is that arbovirus infections and AFI disease surveillance, through the continuation of SEDSS and COPA, will promote evidence-driven public health policy decisions and reduce the burden of disease. The rationale for the current study is that understanding the etiology, epidemiology, and severity of arboviral diseases will allow the United States to be better prepared and respond to critical vector- borne disease outbreaks. The study team will test the central hypothesis by pursuing two specific aims: 1) Explore the natural history of dengue and arboviral infections and other acute febrile illnesses in their differential diagnosis to understand their epidemiology, spectrum of disease, and outcomes to provide recommendations for diagnosis and clinical management, and; 2) Define the correlates of risk and protection of arbovirus transmission in the setting of vector-reduction strategies. Under Specific Aim 1, the team will strengthen hospital surveillance of acute febrile illness (AFI) and maintain an AFI platform for conducting clinical research. For Specific Aim 2, the team will maintain a community-based cohort to assess the incidence and prevalence of arboviral infection, as well as, evaluate the incidence, prevalence, and etiology of other AFIs in selected communities. Central to both aims is the establishment of a data management system and the continuation of strengthening collaborations with the local government, community leaders, and other stakeholders to ensure continuity of the established program. The proposed research is significant because it is expected to deliver robust and broad knowledge regarding the epidemiologic patterns of common arboviral diseases in the context of other AFI of the present and those that may emerge in the geographical setting. Such results provide evidence- based responses to critical questions regarding dengue (and other arboviruses) diagnosis, immune response, and clinical management. Also, the community-based system will be central to evaluate the efficacy of vector control strategies in reducing the incidence of arboviral diseases in humans and assessing its potential use among other populations.",,2025,PONCE SCHOOL OF MEDICINE,3000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P23035,5U01AI151378-04,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,2450928,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23036,3U01AI151378-04S1,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,404857,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23037,5R01AI155562-03,Comprehensive characterization of ancestral populations of the vector Aedes aegypti on Indian Ocean islands,"Project Summary/Abstract We have recently shown that the ancestors of all Aedes aegypti populations in both sub-Saharan Africa as well as around the world presently reside on islands in the Southwest Indian Ocean (SWIO) including Madagascar. These islands gave rise to continental African Ae. aegypti formosus no earlier than about 100,000 years ago. We propose multidisciplinary studies on SWIO populations of Ae. aegypti along with its close relatives, Ae. mascarensis and Ae. pia. This will include population genetics, phylogenetics/phylogeography, vector competence, blood meal analyses, and characterization of the virome of field-caught females. We address question such as: Are the ancestors that gave rise to Ae. aegypti s.s. capable of transmitting the same viruses that cause human diseases? Are these mosquitoes carrying the same viruses in the field and/or do they harbor novel undescribed arboviruses? What are the sources of their blood meals? Where do they breed? Population genetics and phylogenetic preliminary work have already identified candidates for new undescribed species and we suspect more cryptic taxa will be found. We propose to assemble complete genomes for the most informative populations/taxa that will allow comparative studies as well as inference of the ancestral genome of Ae. aegypti s.s., a fundamental resource for analysis of a plethora of genomics studies ongoing in laboratories around the world.",,2026,YALE UNIVERSITY,567551,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P23041,1R01AI175152-01,Olfactory modulation of color vision and behavior in mosquitoes,"PROJECT SUMMARY This application aims to build on our recent discoveries of olfactory “gating” of visual attraction in Aedes aegypti mosquitoes and determine the role of color vision in host and nectar selection. Without vision, mosquitoes cannot track odors, locate hosts, or find mates. Vision is a critical sensory modality involved in long-range olfactory search behaviors and near-host behaviors involved in landing and biting. Despite this potential importance, little is known about vision in anthropophilic mosquitoes and the neural bases of these behaviors. Mosquitoes can see a host from 2-15 m, and our recent findings show that odor “turns on” their visual attraction to hosts, thereby playing a critical role by linking long-distance odor tracking with short-range behaviors near the host. Our work also demonstrated that mosquitoes are sensitive to wavelengths reflected from human skin. However, we lack an understanding of how odor sensitizes the visual system, and the visual preferences of diverse anthropophilic mosquitoes. We have developed new tools to examine olfactory-visual integration, including new Aedes GCaMP6s mosquito lines, the generation of opsin knockout lines, and biogenic amine receptor mutants. This proposal builds on our preliminary findings that demonstrate the importance of color vision and neuromodulators in olfactory-visual integration in mosquitoes. Using semi-field and behavioral assays, calcium imaging in tethered flying mosquitoes, and molecular-genetic approaches, we propose to study the color preferences of mosquitoes and how odor modulates visual neurons. Aim 1 will allow us to characterize the colors (wavelengths) that attract different anthropophilic mosquito species and identify the odors that turn on visual search behaviors. In Aim 2, using Aedes aegypti, we will determine the neural mechanisms by which odors turn on visual search behaviors, and identify the rhodopsins that detect important wavelengths. Our preliminary results indicate that octopamine is critical for olfactory-visual integration. We will generate cell- specific knockout of the octopamine receptor to determine how olfactory-visual behaviors are compromised. In parallel, we will mutate specific long- and short-wavelength rhodopsins to suppress attraction to colors indicating hosts or nectar sources. We will also use new GCaMP6s lines to record from visual neurons in the mosquito brain and characterize how odor modulates those neurons. Aim 3 will test the wavelengths and visual features (motion, object size) that mosquitoes find attractive, and test them in new trap designs in semi-field trials. While there has been extensive work on olfaction in mosquitoes, our work emphasizes that color vision also plays a key role. Olfactory-visual integration is vital in diverse insect vectors, including tsetse flies and kissing bugs. We suggest that our proposed experiments provide a basic framework for understanding how these cues influence haematophagous insects. Furthermore, results from this work will provide information on attractive visual lures, and motivate the identification of molecular targets to cripple visual-olfactory behaviors.",,2028,UNIVERSITY OF WASHINGTON,657511,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P23045,5R01AI155512-03,Regulation of RIG-I signaling and viral immune evasion by ufmylation,"ABSTRACT Type I and III interferons (IFN) restrict RNA virus infection. Infected cells produce IFN through signaling activated by pattern recognition receptors such as RIG-I. Both RIG-I and downstream signaling must be highly coordinated for efficient antiviral responses. As such, these processes are regulated by several post-translational modifications (PTMs). These PTMs are essential for both the activation and eventual termination of RIG-I- signaling. While RIG-I-signaling is coordinated by ubiquitination and phosphorylation, the mechanisms by which other PTMs, such as ubiquitin-like modifiers, may regulate RIG-I-signaling are largely unknown. Our preliminary data reveal that the ubiquitin-like modifier called ufmylation regulates multiple proteins involved in RIG-I signaling for optimal IFN induction in response to viral infection. Further, our data suggest that ufmylation is utilized by viruses to evade the host intracellular innate immune response. Therefore, the goal of this proposal is to determine how ufmylation regulates the intracellular innate immune response to virus infection and viral evasion. Based on our preliminary data, the central hypothesis is that ufmylation modulates the function of host and viral proteins to regulate antiviral innate immunity and viral evasion. Guided by our preliminary data, this hypothesis will be tested by pursuing the following three specific aims: 1) Define how UFL1, the ufmylation E3 ligase, promotes the activation of RIG-I; 2) Understand the molecular mechanism by which ufmylation of a key protein in the RIG-I signaling pathway downregulates its function and signaling; 3) Determine how dengue virus co-opts the ufmylation conjugation system for immune evasion. In Aim 1, the molecular mechanisms by which UFL1 induces the activation of RIG-I in response to RNA virus sensing will be defined. In Aim 2, the mechanism and dynamics of how ufmylation regulates the function of a signaling protein in RIG-I pathway will be determined. In Aim 3, the function by which ufmylation of a DENV protein promotes DENV immune evasion, both in human cell lines and in primary cells, will be determined. Taken together, the work proposed in this application will be significant and innovative because it will attribute a novel immune regulatory function to ufmylation, contribute to our understanding of its basic functions, and uncover a novel control (ufmylation) of antiviral innate immunity. Additionally, this work will provide understanding of a host-directed process that is utilized by viruses for immune evasion to facilitate viral replication. Overall, this work will define a new PTM that coordinates the RIG-I signaling pathway, which will improve our knowledge of both antiviral immunity and regulation of innate immune pathways that will lead to increased understanding of the mechanistic causes of dysregulated IFN that can ultimately result in autoimmune disease. It will also define a new mechanism of immune evasion by flaviviruses that will have implications for therapeutic and vaccine strategies to limit their infection.",,2026,DUKE UNIVERSITY,456729,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P23053,5R25AI164613-03,"Frontiers in Emerging, Reemerging and Zoonotic Diseases and Diversity (FrERZD2)","PROJECT SUMMARY Our nation is nearly paralyzed by the twin pandemics of COVID-19 and painful inequities in health outcomes among COVID-19 infected Americans of differing ethnicities. To help address these, we seek sponsorship to train the next generation of pandemic and emerging disease researchers in the FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY. FrERZD2 will launch and sustain three vital undertakings: sophisticated courses for skills development; relevant vital research experiences; and career mentoring activities. Responsive to PAR-20-289, it is designed for 16 trainees who are graduate and medical students, medical residents, postdoctoral fellows, and/or early-career faculty, and who also are US citizens or permanent residents. The week-long course will help to ensure that clinically active scientists (especially physicians) are able to obtain permission to participate. Too few laboratories are led by under-represented minority (URM) scientists, and not enough new URM trainees graduate. We seek 5 years of sponsorship to offer FrERZD2 courses at Morehouse School of Medicine (MSM), an HBCU, in 2021, 2023, and 2025 and Ponce Health Sciences University (PHSU), a Hispanic-Serving Institution, in 2022 and 2024. Under the overall directorship of Gerald Schatten from Pittsburgh, along with Jonathan Stiles at MSM, Idhaliz Flores from PHSU, and Calvin Simerly, also from Pittsburgh, FrERZD2 is overseen by an external scientific advisory committee. It offers dynamic advanced training courses consisting of daily lectures on emerging concepts, followed by extended discussion, laboratory research, technologically intense workshops, and informal seminars. Our similar training programs have recruited participants of whom 34% self-identify as African American/Black and 30% as Hispanic Americans; 66% are women, and 62% are from URM institutions. Six specific aims are proposed. Aim 1. Provide conceptual education and experimental training. Aim 2. Provide background information and self-reflective exercises and demonstrations to understand, appreciate, and address the historic and current underpinnings of inequities in the research workforce’s diversity and disparities in health care. Aim 3. Sponsor meaningful mentored research. Aim 4. Discuss career planning. Aim 5. Educate participants on the responsible conduct of research. Aim 6. Provide unbiased, quantitative, independent mechanisms to track trainees’ careers, comprehensively and longitudinally. The program’s name, FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY, acknowledges our hope that the COVID pandemic may soon recede significantly and our realization that other emerging, reemerging, and zoonotic diseases will arise that must be timely addressed. Overall, in conducting this program, we will continue to enhance and expand the research careers of the most promising scientists, with sensitivity to ensuring full diversity in the NIAID workforce.",,2026,MAGEE-WOMEN'S RES INST AND FOUNDATION,339875,Human Populations,Black | Other,Adults (18 and older),Unspecified,Other,Other,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +P23057,5K08NS119882-02,Viral Neurobiology in the Prenatal Brain,"ABSTRACT The prenatal brain is uniquely susceptible to viral infections. Such infections threaten 1 in 4 pregnancies and can cause severe neurodevelopmental disorders if not fetal demise. Different viruses lead to strikingly similar clinical outcomes due to overlapping viral neuropathology and the host’s common neuronal response. Such a reality calls for the development of urgently needed prenatal standards of care for prevention or treatment of virally induced brain injury. This need requires a much-deeper understanding of the corresponding neurobiology. A key regulator of the host’s common neuroviral response is the mechanistic target of rapamycin (mTOR) through essential roles in viral autophagy, which affect viral clearance and neuronal survival. There is unsettled controversy, however, about whether mTOR expression and viral autophagy are key defenses against, or requisites to, viral replication and neuronal injury. The PI has new preliminary data connecting mTOR with a novel neuroviral response gene, Hexosaminidase B (HEXB), and suggesting new cellular functions for this genetic complex in activating prenatal viral autophagy to prevent brain injury. Opening new research windows for therapeutic intervention, this sets the context for the proposed K08 study, which rigorously tests the guiding hypothesis that neurodevelopmental gene expression affects prenatal viral susceptibility toward brain injury. Purusing three integrated and synergistic aims in cellular, mouse, and human systems, the PI will investige how gene expression of mTOR and HEXB affects prenatal viral susceptibility and how it might be altered to prevent brain injury. First, human-derived organoids are used to study how expression of mTOR and HEXB affects viral clearance, neuronal survival, and up/downstream pathways (Aim 1). In parallel, this relationship is prenatally evaluated in vivo to determine its impact on postnatal development (Aim 2). Mirrored allelic series of mTOR and HEXB are genetically cross-titrated in these aims, which will shed light on a population genomic analysis to study the extent to which variants in these genes/pathways affect prenatal susceptibility to brain injury (Aim 3). This K08 grant combines research using synergistic/integrated systems with theoretical and technical training by seasoned mentors in neurobiology, neurovirology, and genomics at Children’s National Hospital and NINDS. The individually tailored career development plan uniquely positions the PI, a board-certified prenatal-neonatal critical care neurologist-scientist, to open multiple new research windows into the developing human brain by: (a) deepening our fundamental understanding of prenatal neurovirology and the crticial role of neuro- developmental genes (mTOR & HEXB), regulatory networks, and essential cellular functions; (b) examining genetic regulation of prenatal viral autophagy as a cornerstone for prenatal precision medicine; and (c) tapping into a robust neuroepidemiology research infrastructure (Consortium, CDC, NIH) to identify prenatal susceptibilities. The ultimate goal is to understand the connection between viral neurobiology and neuronal injury in the developing brain to optimize the neuropsychological life experience of future generations of children.",,2027,CHILDREN'S RESEARCH INSTITUTE,215730,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2022 +P23058,5R01HD105474-02,Jump Start+:COVID Support to improve resiliency and mitigate risks in childcare centers serving children from low-income ethnic minority backgrounds.,"Background. This is a Type 1 hybrid effectiveness-implementation trial studying the role of a community- based, childcare center-support system in improving resilience and mitigating the long-term impacts of the pandemic on child development. Public health disasters have disproportionate and long-term impacts on poor, disenfranchised communities. Miami-Dade County has one of the US's highest rates of chronic poverty, is minority majority, and has been an epicenter of the pandemic. COVID-19 is having psychosocial impacts on children that is producing anxiety, irritability, anger, and depression. Teachers in childcare centers continue to be overwhelmed by changing guidelines and how to address the downstream psychological effects children are experiencing. While numerous resources exist that can help childcare centers with disaster recovery, the information can be overwhelming and difficult to navigate, and research is yet to show the actual benefits of the resources. Approach. We will leverage our existing community-based intervention, Jump Start, with its extensive reach in Miami-Dade County, to childcare centers participating in the County’s Quality Improvement System. This system prioritizes children living in poverty who are at highest risk for problems. This study will be modeled on a successful Early Childhood Mental Health Consultation (ECMHC) intervention which utilizes mental health consultants to deliver a Jump Start+: COVID Support virtual toolkit to childcare centers via a Kubi robot. The toolkit is comprised of four strength-based strategies likely to be effective in improving resiliency following disasters: Safety Planning, Effective Communication, Adult Self-Care, and Trauma-Informed Behavior Support. We will use Reach, Effectiveness-Adoption, Implementation, Maintenance (RE-AIM) framework to guide the evaluation of our Type 1 hybrid design. Our first aim will utilize a cluster randomized trial to examine the effectiveness of Jump Start+: COVID Support on improving the psychosocial functioning of young children, as compared to an obesity-prevention intervention control group. Child development is the primary outcome, with children followed at 6, 12,18, and 24 months. The second aim will examine the mechanisms that contribute to effective teachers’ uptake of Jump Start+: COVID Support strategies on child outcomes. The third aim will explore implementation barriers/facilitators as well as potential societal contextual factors (e.g., vaccine uptake) to help centers serving disproportionately affected minority communities recover from and prepare for future crises. Impact. These aims meet a high-priority research area for NICHD because they address the social and environmental factors that can enhance children’s resilience. Employing a Type 1 hybrid design will inform the refinement and scaling of Jump Start+: COVID Support and generalize impacts to other childcare center interventions in the context of disasters. We have the potential to influence long-term trajectories of childcare center practices and child development which, in turn, can chart a course for future child health and well-being in the face of crises.",,2025,UNIVERSITY OF MIAMI SCHOOL OF MEDICINE,645468,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Social impacts | Vaccine/Therapeutic/ treatment hesitancy,2022 +P23061,1S10OD030381-01A1,7T Cryogen-Free Preclinical MRI for small animals to study infectious diseases in BSL-3 containment,"Infectious diseases are a major threat to humanity, and new tools are needed to study disease pathogenesis and aid the development of novel diagnostics, biomarkers and therapeutics. The alarming rise of highly virulent and multi-drug resistant (MDR) pathogens, their rapid spread, global pandemics such as COVID-19 and continued life-threatening nosocomial infections in hospitals, remain as major challenges to human health. Tomographic molecular imaging enables rapid, noninvasive visualization, localization and monitoring of molecular processes deep within the body and offers several advantages over traditional tools used for the study of infectious diseases. We are requesting a 7T Cryogen-Free preclinical Magnetic Resonance Imaging (MRI) system manufactured by MR Solutions (model 7024) to study infectious diseases in biosafety level-3 (BSL-3) containment at a centralized core facility. Since 2009, the Johns Hopkins Center for Infection and Inflammation Imaging Research (Ci3R) has developed and supported preclinical molecular imaging (PET, SPECT, CT) for infections and inflammatory disorders and established an entirely new user base comprising several NIH- funded infectious diseases investigators within the Johns Hopkins University. While many investigators study Mycobacterium tuberculosis and more recently SARS-CoV-2 â€Â"" both of which are designated as BSL-3 pathogens with special biosafety needs â€Â"" Ci3R also supports other researchers that study MDR bacteria (e.g. MRSA) and viral agents such as Zika. Several new approaches for infection imaging have been developed at Ci3R and translated to the clinic. MRI has many advantages over radiopharmaceutical imaging, including high-spatial resolution and contrast. 1H and 19F MR spectroscopic imaging (19F MRSI) and chemical exchange saturation transfer (CEST) contrast would support complementary approaches for molecular imaging of infectious diseases. Therefore, the addition of a high-field preclinical MRI will greatly boost the research efforts related to infectious diseases imaging, while also leveraging the strong MRI expertise within Johns Hopkins University led by NIH-funded investigators. Imaging technologies for infectious diseases are an emerging field of research and overcome several fundamental limitations of current tools in infectious diseases. Therefore, these technologies can have a broad impact on both basic research and patient care. Beyond diagnosis and monitoring infections, these technologies will also provide a uniform cross-species platform for animal studies, allow unique insights into understanding disease pathogenesis and expedite bench-to-bedside translation of new therapeutics. Finally, since MRI is readily available for humans, including high-field 7T systems, validated techniques may become valuable tools for clinical applications in infectious diseases and for enabling precision medicine.",,2024,JOHNS HOPKINS UNIVERSITY,1695141,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2022 +P23062,2R01AI133348-06,Mechanisms of viral RNA maturation by co-opting cellular exonucleases,"PROJECT SUMMARY Flaviviruses are single-stranded positive-sense RNA viruses that include dangerous human pathogens like dengue, West Nile, Yellow Fever, Zika, and many others. During infection, these viruses produce a set of non- coding RNAs called ‘subgenomic flavivirus RNAs’ (sfRNAs) that interact with cellular proteins to manipulate the cellular environment, to include inhibiting the antiviral response. sfRNAs have been directly linked to cytopathic and pathogenic outcomes, and viruses that cannot produce sfRNAs are attenuated, motivating efforts to understand the mechanism of xrRNA production. sfRNAs are made when cellular 5’à3’ exoribonucleases (in particular, Xrn1) processively degrade the viral genomic RNA but then halt at specifically structured RNA elements in the viral 3’ UTR called exoribonuclease resistant RNAs (xrRNAs). By solving the structures of multiple xrRNAs by x-ray crystallography and combining this with biochemistry, biophysics, and virology, we showed that xrRNAs fold into a unique ring-like topology that creates a mechanical block the exoribonuclease cannot pass through. Furthermore, we used our discoveries to classify xrRNAs and to find new examples associated with both non-coding and coding RNAs. These successes now define several new questions. First, xrRNAs are often found in multiple copies ‘in tandem’ where their function is coupled in some way, but the structural basis of this coupling, and the effects of breaking the coupling on both sfRNA formation and viral infection kinetics, are unknown. Second, although we have a good understanding of several classes of xrRNAs, we have yet to solve the structure of an xrRNA from a tick-borne flavivirus, which appear to have interesting and unique properties. Third, although we have found many new examples of xrRNAs, it appears there are many more that are undiscovered, and we also do not understand how the various classes of xrRNA relate evolutionarily. How do these structures diversify and evolve in 3-D given the tight constraints on their folding? Here, we propose to answer these questions in three aims, employing a strategy that combines biochemistry, x- ray crystallography, cryo-EM, virology, and in vitro selections coupled with computational tools. The research described here will contribute significant basic knowledge regarding an important molecular process of broad applicability to viral disease, a necessary step between the discovery of a mechanism and the targeting of it for therapeutic intervention.",,2023,UNIVERSITY OF COLORADO DENVER,453074,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P23063,5R01DC018403-03,The taste of ribonucleosides: The molecular and cellular basis underlying chemosensory detection of previously unknown macronutrients,"Insects are the most abundant class of animals, next to vertebrates. For example, the biomass of termites alone equals that of humans, the most abundant mammal. There are about 1 million named insect species and approximately another 5 million yet to be classified, compared to about 66,000 species of vertebrates. While overall beneficial to our ecosystem, some insects have considerable negative impact on human health. Disease vectors, mostly flies and mosquitoes, are major transmitter of microbes that cause devasting human diseases, including yellow fever, dengue, malaria and zika. These insect vectors kill close to a million people each year, sicken hundreds of millions more and incur billions of dollars annually in costs for treatment and lost productivity. Other insect species are agricultural pests and consume crops and fruits of cultivated plants, leading to famine in many parts of the world. In light of these facts, a better understanding of insect biology and behavior, in particular chemosensory behavior, is paramount for developing specific and effective strategies for population control of harmful pests. Drosophila melanogaster, with its array of experimental tools, is uniquely suited to uncover the basic principles underlying these behaviors. Like mammals and other insects, Drosophila depend on chemosensory systems to navigate their external world appropriately. The sense of taste is particularly important to identify food sources and avoid harmful chemicals. To assure that all essential food chemicals are consumed, insects have evolved appetitive taste receptors for the three major macronutrients, proteins, carbohydrates and fats. Intriguingly, Drosophila larvae, in contrast to adult flies, can also sense ribonucleosides and RNA in their food. These chemicals represent an essential resource required to support rapid growth and survival during the fast-growing larval stages. Larvae employ a small number of closely related taste receptors, the Gustatory Receptors (Grs) 28 to detect these chemicals. The Gr28 genes are among the most conserved insect taste receptor genes, homologs of which are found in all insect genomes, from flour beetles to honeybees to mosquitoes. These observations suggest that the Gr28 genes have a conserved role, namely to detect RNA and ribonucleosides in insects. Remarkably, some of the Gr28 genes have been implicated in temperature and light sensing, expanding their role to sensory pathways beyond taste. Thus, an in-depth understanding of the function of receptors for RNA and ribonucleosides is of considerable interest, especially because they are broadly conserved in diverse insect species, from disease vectors (mosquitoes and flies), to agricultural pests (beetles, grasshoppers) and ecologically beneficial pollinators (honeybees). Exploiting the ability of insects to sense RNA and ribonucleosides via specific taste receptors may provide new opportunities to develop strategies for control of harmful insects.",,2025,TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR,376699,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P23064,5UC2GM141586-02,Developing a Culture of Biomedical Research at the University of the Virgin Islands,"PROJECT SUMMARY This proposal will enhance and innovate the biomedical research infrastructure and training at the University of the Virgin Islands (UVI), the only higher educational institution in the US Virgin Islands (USVI). The overall objective of this proposal is to provide the highest level of sponsored program services for biomedical research by developing a culture of research through training, mentoring, collaboration and a strong infrastructure. UVI’s vision is to develop research resulting in an increase in the number of faculty conducting excellent externally funded biomedical research who will be able to mentor undergraduate students with potential for careers in science. There are several motivating factors for this project: (1) Diversity in the scientific workforce is key to the future biomedical discoveries that will improve the health of the Nation, and HBCUs such as UVI have an important role to play in training students who are underrepresented in science. (2) The USVI is a medically underserved area that experiences dramatic health disparities and emerging diseases including dengue, chikungunya, Zika, and the more recent coronavirus, which are important not only in the Caribbean but are also increasing on the US mainland. Little research on population health has been performed in the USVI and UVI continues to look at research in these areas. (3) Extensive undergraduate research experience is essential to prepare students for highly competitive doctoral programs. Although UVI has very successful programs that mentor undergraduates in research, there are many more UVI students interested in research experience than can be accommodated in externally funded research laboratories. (4) UVI has established a culture of innovation in its 2018-2023 Strategic Plan and through this research infrastructure and innovation is a primary focus area and is supported by the President and senior leadership. The UVI Institutional Development Plan (IDP) addresses barriers to research and informs the Specific Aims of this proposal: (1) Develop UVI’s research administration leadership and organization such that it is well-trained, resourced, and motivated to support a culture of research. (2) Develop research review and training programs for research faculty to increase the number and improve the competitiveness of proposal submissions (3) Increase mentorship and training opportunities for undergraduates in biomedical research by supporting faculty to receive external funding. This program is innovative because it will fully integrate the IDP for research within UVI’s 2018-2023 Strategic Plan, providing strong institution-wide commitment. Research and training innovations include targeted training initiatives covering the life cycle of research, increased outreach efforts, training and grant writing initiatives and focus groups of HBCU research administrators to overcome the barrier of geographic isolation. UVI’s logic model will be used to ensure that each activity will contribute to a sustainable vision for research and to developing a University-wide culture supporting research.",,2024,UNIVERSITY OF THE VIRGIN ISLANDS,292003,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research on Capacity Strengthening,Individual level capacity strengthening | Institutional level capacity strengthening,2021 +P23066,5R01AI167300-02,Sublingual Supramolecular Vaccines and Immunotherapies,"Even when vaccines are rapidly developed and shown to be efficacious and safe, vaccination campaigns continue to be hampered by public hesitancy and by challenges distributing vaccines equitably around the globe. Vaccine hesitancy, where individuals refuse or delay vaccination, has been a persistent challenge, affecting a third to a quarter of individuals in the US and globally. Inequitably, it affects racial and ethnic minority communities particularly strongly, and in 2019 the World Health Organization named vaccine hesitancy as one of the top-ten threats to global health. Needle-based injections, which increase vaccine reactogenicity, are a significant driver of vaccine hesitancy. A second fundamental hurdle in equitable availability of vaccines involves the chain of distribution. Most vaccines must be transported and stored within a continuous cold-chain to prevent loss of potency, making global distribution challenging. In the face of these limitations, lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking vaccines, yet the issues of global distribution and patient acceptance are exponentially more challenging with repeated dosing. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered specifically for the sublingual route to provide for effective vaccination. The project aims to design a shelf- stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of- concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of immune responses remain to be articulated. Therefore the objective of the project is to articulate these design rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size, charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza, zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).",,2026,DUKE UNIVERSITY,435245,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Orthomyxoviridae,Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2021 +P23067,5R01AI165575-02,Opsins and TRP channels controlling sensation and behavior in Aedes aeygpti,"Abstract The mosquito Aedes aegypti spreads diseases such as dengue, Zika, yellow fever, and others that afflict >100 million people each year. These mosquitoes rely on multiple keen senses to locate human hosts for blood meals, and for finding conspecifics for mating. Currently, we have only a rudimentary understanding of the receptors that control these critical behaviors. The goal of the proposed research is to address this gap. The unifying theme of this proposal is to test the idea that opsins and TRP channels are two key classes of signaling proteins that have broad roles in sensation and in controlling behavior in Ae. aegypti. Rhodopsins are the founding G-protein coupled receptors (GPCRs). We recently discovered that opsins are multi-modal sensory receptors, challenging 100 years of dogma that they detect only light. To find humans, female Ae. aegypti integrate information from diverse stimuli, including CO2, visual cues, organic molecules, and convection heat from skin. We discovered another cue. Aim 1 builds on our preliminary data that Ae. aegypti use infrared (IR) radiation as an additional host stimulus. We outline experiments to reveal the roles of opsins and the TRPA1 channel in IR detection. We propose to identify the IR-sensing neurons that express the opsins and TRPA1, and to test a model to explain the role of opsins in IR sensation. To pursue this aim, we devised a highly effective assay for monitoring IR attraction and a new molecular genetic approach to bypass difficulties in combining multiple genetic elements. Aim 2 takes advantage of a mutation that we created in another TRP (TRPV-A), which renders males and females deaf. We will test the roles of hearing and TRPV-A in swarm formation, in mating, and in finding humans. Aim 2 will also build on the observations that male mating requires audition mediated by TRPV-A to devise a strategy to overcome a major impediment limiting the efficacy of the sterile insect technique (SIT). SIT is a promising strategy to suppress Ae. aegypti. It involves inundating a local population with sterile males, which then render females sterile upon mating. An obstacle to using SIT is that wild-type males outcompete sterile males. We propose that manipulation of the activity of the TRPV-A- expressing auditory neurons elevates sterile male mating success, and will thereby increase the efficacy of SIT in suppressing Ae. aegypti. Aim 3 concerns identifying the sensory receptors for repellents. We propose to test the idea that an opsin functions as a highly sensitive receptor for insect repellents. If confirmed by the proposed experiments, this would demonstrate that opsins comprise a new class of olfactory receptor. To accomplish our goals, we have developed an extensive repertoire of state-of-the-art approaches. These include new molecular genetic tools, a suite of behavioral assays, original video tracking software, and in vivo electrophysiological recordings. In summary, this project will reveal the roles of opsins and TRP channels in allowing mosquitoes to sense humans and conspecific mates. The insights gleaned from this work have exciting potential to lead to innovative strategies to control Ae. aegypti and reduce insect-borne disease.",,2026,UNIVERSITY OF CALIFORNIA SANTA BARBARA,555006,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P23069,5U01DP006623-02,Maryland Pregnancy Risk Assessment Monitoring System (PRAMS),"Pregnancy Risk Assessment Monitoring System (PRAMS) in Maryland Executive Summary, July 2020 Background-The Maternal and Child Health Bureau and the Vital Statistics Administration have worked jointly to implement the Maryland PRAMS project since 2000 through a cooperative agreement with the Centers for Disease Control and Prevention (CDC). PRAMS surveys mothers 2-9 months after delivery about factors before, during, and shortly after pregnancy that may have an impact on pregnancy outcome. The program has also proven its capacity to implement survey supplements on emerging issues including the influenza vaccine, Zika, disability, and opioid use. The Maryland PRAMS survey booklet is sent monthly to a sample of new mothers along with an incentive (manicure file). The survey questionnaire, as well as other PRAMS materials, is available in both English and Spanish. Each mother is sent up to three surveys followed by a telephone interview if no written surveys have been returned. A $100 gift card is given out monthly to a mother chosen randomly who has completed the mail or phone survey. Maryland currently utilizes a stratified random sample based on infant birth weight (over-selecting mothers who have delivered a low birth weight infant under <2500 grams). Program Features-Maryland PRAMS data are analyzed annually and currently include reports from 2001 to 2017 birth years. Focus Briefs on various topics are posted on the PRAMS website at www.marylandprams.org. Human Subjects Training occurs annually for all PRAMS staff and was last completed in July 2020. Number of Mothers Served-Approximately 2,000 new mothers are surveyed annually. As of June 2020, 44,714 new mothers in Maryland have been mailed the PRAMS survey since its inception. Annual weighted response rates from 2001-2017 births have met or exceeded the threshold. Budget-Maryland PRAMS is currently funded at $172,500 annually ($157,500 in core funding and $15,000 in supplemental disability funding). We are currently in year five of a five year cycle. This competitive application is for year one of the next 5 year grant cycle. We will be requesting the ceiling award amount of $175,000.",,2026,MARYLAND STATE DEPARTMENT OF HEALTH,160020,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P23071,1S06GM146125-01,UA Project: Advancing Vector-borne Disease Surveillance in American Indian Communities,"Project Summary/Abstract The Inter Tribal Council of Arizona, Cocopah Environmental Protection Office staff, medical entomologists from the University of California, vector-borne disease researchers from the University of Arizona and other community partners will build upon existing participatory research and outreach partnerships in the proposed project. Arizona often ranks amongst the highest in West Nile virus infection and related deaths relative to other states. Additionally, high populations of the invasive yellow fever mosquito Aedes aegypti in communities along southern border areas makes mosquito and pathogen surveillance critically important. Ae. aegypti is the primary vector of dengue and Zika viruses which circulate in the neighboring border states of Sonora and Baja California, Mexico. Ticks are important vectors causing human disease. Among the most significant is Rocky Mountain spotted fever (RMSF), a bacterial infection caused by Rickettsia rickettsii, which kills more people in North America than any other tickborne disease. Native American populations are disproportionately impacted. Since the first locally acquired case was identified in Arizona in 2003, the disease has become endemic in many Native American communities. In Arizona, R. rickettsii is vectored by the brown dog tick Rhipicephalus sanguineus and to date there have been more than 436 cases of RMSF with a case fatality rate of 10%, which is 15 times the national rate for this disease. There have been no surveillance efforts for vector or pathogen prevalence outside of post-epidemic events. Supportive efforts are needed to identify high-risk surveillance gaps, undertake vector and pathogen prevalence assessments, and generate access to essential infrastructure and services in the short-term. Vector-borne Disease Research Committees (VbDRC) within collaborating tribal communities will direct high priority vector surveillance and inform Tribal leadership of technical findings. Creation of Vector Risk Mitigation Plans and relevant community specific practicum training will be provided for tribal environmental health, public health and medical practitioners serving communities. Additionally, investment in Native American students through financially supported vector research experiences will help build the future public and environmental health workforce. There is strong evidence that student research experiences improve educational persistence, thus UA faculty and VbDRC members will mentor Native American students through community-based research projects.",,2026,"INTER TRIBAL COUNCIL OF ARIZONA, INC.",107239,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease surveillance & mapping,2022 +P23072,5R01AI155562-02,Comprehensive characterization of ancestral populations of the vector Aedes aegypti on Indian Ocean islands,"Project Summary/Abstract We have recently shown that the ancestors of all Aedes aegypti populations in both sub-Saharan Africa as well as around the world presently reside on islands in the Southwest Indian Ocean (SWIO) including Madagascar. These islands gave rise to continental African Ae. aegypti formosus no earlier than about 100,000 years ago. We propose multidisciplinary studies on SWIO populations of Ae. aegypti along with its close relatives, Ae. mascarensis and Ae. pia. This will include population genetics, phylogenetics/phylogeography, vector competence, blood meal analyses, and characterization of the virome of field-caught females. We address question such as: Are the ancestors that gave rise to Ae. aegypti s.s. capable of transmitting the same viruses that cause human diseases? Are these mosquitoes carrying the same viruses in the field and/or do they harbor novel undescribed arboviruses? What are the sources of their blood meals? Where do they breed? Population genetics and phylogenetic preliminary work have already identified candidates for new undescribed species and we suspect more cryptic taxa will be found. We propose to assemble complete genomes for the most informative populations/taxa that will allow comparative studies as well as inference of the ancestral genome of Ae. aegypti s.s., a fundamental resource for analysis of a plethora of genomics studies ongoing in laboratories around the world.",,2026,YALE UNIVERSITY,576486,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P23073,5U01CK000580-03,PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ARBOVIRUSES (PRESCA) PROGRAM,"PROJECT SUMMARY The impact of infections transmitted by mosquitoes is global. Arboviral diseases such as dengue, chikungunya, and Zika are a significant health concern due to the expanding geographical range of many mosquito species. Emphasis on disease surveillance systems is central to evaluate the effectiveness of primary and secondary dengue prevention methods and strategies, including the introduction of dengue vaccines and new vector control methods. In the current application, the study team will address specific and fundamental gaps in the diagnosis and clinical management of dengue and other acute febrile illnesses (AFI); ultimately, evaluating the efficacy of vector control strategies in reducing the incidence of arbovirus infection through a combination of both clinic- and community-based surveillance systems. The study team’s long-term goal is to mitigate arboviral and other AFI disease burdens by improving diagnosis, clinical management, and prevention strategies. The study’s central hypothesis is that arbovirus infections and AFI disease surveillance, through the continuation of SEDSS and COPA, will promote evidence-driven public health policy decisions and reduce the burden of disease. The rationale for the current study is that understanding the etiology, epidemiology, and severity of arboviral diseases will allow the United States to be better prepared and respond to critical vector- borne disease outbreaks. The study team will test the central hypothesis by pursuing two specific aims: 1) Explore the natural history of dengue and arboviral infections and other acute febrile illnesses in their differential diagnosis to understand their epidemiology, spectrum of disease, and outcomes to provide recommendations for diagnosis and clinical management, and; 2) Define the correlates of risk and protection of arbovirus transmission in the setting of vector-reduction strategies. Under Specific Aim 1, the team will strengthen hospital surveillance of acute febrile illness (AFI) and maintain an AFI platform for conducting clinical research. For Specific Aim 2, the team will maintain a community-based cohort to assess the incidence and prevalence of arboviral infection, as well as, evaluate the incidence, prevalence, and etiology of other AFIs in selected communities. Central to both aims is the establishment of a data management system and the continuation of strengthening collaborations with the local government, community leaders, and other stakeholders to ensure continuity of the established program. The proposed research is significant because it is expected to deliver robust and broad knowledge regarding the epidemiologic patterns of common arboviral diseases in the context of other AFI of the present and those that may emerge in the geographical setting. Such results provide evidence- based responses to critical questions regarding dengue (and other arboviruses) diagnosis, immune response, and clinical management. Also, the community-based system will be central to evaluate the efficacy of vector control strategies in reducing the incidence of arboviral diseases in humans and assessing its potential use among other populations.",,2025,PONCE SCHOOL OF MEDICINE,2495042,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P23074,5U01AI151378-03,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,2474236,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23080,5R01AI155512-02,Regulation of RIG-I signaling and viral immune evasion by ufmylation,"ABSTRACT Type I and III interferons (IFN) restrict RNA virus infection. Infected cells produce IFN through signaling activated by pattern recognition receptors such as RIG-I. Both RIG-I and downstream signaling must be highly coordinated for efficient antiviral responses. As such, these processes are regulated by several post-translational modifications (PTMs). These PTMs are essential for both the activation and eventual termination of RIG-I- signaling. While RIG-I-signaling is coordinated by ubiquitination and phosphorylation, the mechanisms by which other PTMs, such as ubiquitin-like modifiers, may regulate RIG-I-signaling are largely unknown. Our preliminary data reveal that the ubiquitin-like modifier called ufmylation regulates multiple proteins involved in RIG-I signaling for optimal IFN induction in response to viral infection. Further, our data suggest that ufmylation is utilized by viruses to evade the host intracellular innate immune response. Therefore, the goal of this proposal is to determine how ufmylation regulates the intracellular innate immune response to virus infection and viral evasion. Based on our preliminary data, the central hypothesis is that ufmylation modulates the function of host and viral proteins to regulate antiviral innate immunity and viral evasion. Guided by our preliminary data, this hypothesis will be tested by pursuing the following three specific aims: 1) Define how UFL1, the ufmylation E3 ligase, promotes the activation of RIG-I; 2) Understand the molecular mechanism by which ufmylation of a key protein in the RIG-I signaling pathway downregulates its function and signaling; 3) Determine how dengue virus co-opts the ufmylation conjugation system for immune evasion. In Aim 1, the molecular mechanisms by which UFL1 induces the activation of RIG-I in response to RNA virus sensing will be defined. In Aim 2, the mechanism and dynamics of how ufmylation regulates the function of a signaling protein in RIG-I pathway will be determined. In Aim 3, the function by which ufmylation of a DENV protein promotes DENV immune evasion, both in human cell lines and in primary cells, will be determined. Taken together, the work proposed in this application will be significant and innovative because it will attribute a novel immune regulatory function to ufmylation, contribute to our understanding of its basic functions, and uncover a novel control (ufmylation) of antiviral innate immunity. Additionally, this work will provide understanding of a host-directed process that is utilized by viruses for immune evasion to facilitate viral replication. Overall, this work will define a new PTM that coordinates the RIG-I signaling pathway, which will improve our knowledge of both antiviral immunity and regulation of innate immune pathways that will lead to increased understanding of the mechanistic causes of dysregulated IFN that can ultimately result in autoimmune disease. It will also define a new mechanism of immune evasion by flaviviruses that will have implications for therapeutic and vaccine strategies to limit their infection.",,2026,DUKE UNIVERSITY,456729,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P23086,5K99GM141482-02,"The role of mitochondrial/ER contacts in the regulation of mtDNA release from mitochondria, innate immune signaling, and responses to viral infection","PROJECT SUMMARY Innate immunity is critical for human health, allowing cells to detect and combat invasion by pathogens. Mitochondria are essential organelles that play important roles within the regulation of innate immune pathways. Contact sites between mitochondria and the endoplasmic reticulum (mitochondria/ER contacts, or MERCs) are important for mitochondrial homeostasis (such as replication of mitochondrial DNA, or mtDNA), but also act as signaling platforms for antiviral responses to viral dsRNA. However, the role of MERCs in the regulation of innate immune responses to cytoplasmic DNA is not well understood. In addition, mtDNA activates innate immune pathways when released from mitochondria into the cytoplasm. Dr. Laura Newman has found that MERCs stimulate the release of mtDNA in response to stalled mtDNA replication caused by mtDNA damage. Though it is well-established that cytoplasmic mtDNA enhances antiviral defenses, whether MERCs regulate mtDNA release during viral infection is unknown. Certain DNA viruses (HSV-1 and EBV) damage mtDNA directly or inhibit its replication, suggesting that removal of mtDNA (and its antiviral properties) may aid viral replication. This provides an ideal model system to test whether MERCs mediate release of damaged mtDNA during infection. In addition, RNA viruses disrupt the ER and MERCs to replicate. Release of mtDNA from mitochondria occurs during infection by several RNA viruses (such as influenza); therefore, MERCs may also mediate mtDNA release in response to RNA viral infection. The central hypothesis is that MERCs regulate mtDNA release and coordinate dsRNA and DNA innate immune responses to amplify cellular antiviral defenses. Aim #1 examines whether MERCs stimulate mtDNA release during HSV-1 or EBV infection, and whether mtDNA release into the cytosol benefits the host cell or virus. Aim #2 builds upon Dr. Newman’s preliminary data that the mitochondrial protein MFN1 enhances innate immune responses to cytoplasmic DNA, and tests whether MFN1 complexes with two innate immune adaptors that sense DNA (STING) and dsRNA (MAVS) at MERCs to regulate antiviral defenses. Lastly, Aim #3 examines whether RNA viruses (Influenza A and SARS-CoV-2) disrupt MERCs, causing stalled mtDNA replication and release, and whether this enhances antiviral defenses. Successful completion of any aim will provide important insights into the regulation of antiviral defenses, possibly informing new therapeutic targets to limit viral infection. This research will also provide virology training to the candidate, and research on viral-mitochondrial interactions will be carried over to her own lab. This award will enable Dr. Newman to take advantage of virology and immunology expertise via her advisory committee (Drs. O’Shea and Kaech), as well as additional career development opportunities at the Salk Institute. This will aid her transition to an independent scientist specializing in the role of mitochondria within innate immune pathways, which is a rapidly expanding and important area of scientific research.",,2023,SALK INSTITUTE FOR BIOLOGICAL STUDIES,100000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P23087,3UM1AI148684-03S7,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) - COVAIL DMID #22-0004,"IDCRC LG Project Summary/Abstract: This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a collaborative national partnership of leading infectious diseases (ID), human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the LG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research includes interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting infectious diseases. The LG’s experts and their programs have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority ID’s. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and leverages NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts has established and operates with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the LG is composed of a Leadership Operations Center including Expert Working Groups, Key Function Committees, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in ID clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations has allowed it to respond rapidly (surge capacity) t o t h e C O V I D - 1 9 public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The LG and the institutions represented are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2026,EMORY UNIVERSITY,240086,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P23088,3UM1AI148684-03S4,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,2969015,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P23090,3UM1AI148684-03S3,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,2018048,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P23091,3R25AI164613-01S1,"Frontiers in Emerging, Reemerging and Zoonotic Diseases and Diversity (FrERZD2)","PROJECT SUMMARY Our nation is nearly paralyzed by the twin pandemics of COVID-19 and painful inequities in health outcomes among COVID-19 infected Americans of differing ethnicities. To help address these, we seek sponsorship to train the next generation of pandemic and emerging disease researchers in the FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY. FrERZD2 will launch and sustain three vital undertakings: sophisticated courses for skills development; relevant vital research experiences; and career mentoring activities. Responsive to PAR-20-289, it is designed for 16 trainees who are graduate and medical students, medical residents, postdoctoral fellows, and/or early-career faculty, and who also are US citizens or permanent residents. The week-long course will help to ensure that clinically active scientists (especially physicians) are able to obtain permission to participate. Too few laboratories are led by under-represented minority (URM) scientists, and not enough new URM trainees graduate. We seek 5 years of sponsorship to offer FrERZD2 courses at Morehouse School of Medicine (MSM), an HBCU, in 2021, 2023, and 2025 and Ponce Health Sciences University (PHSU), a Hispanic-Serving Institution, in 2022 and 2024. Under the overall directorship of Gerald Schatten from Pittsburgh, along with Jonathan Stiles at MSM, Idhaliz Flores from PHSU, and Calvin Simerly, also from Pittsburgh, FrERZD2 is overseen by an external scientific advisory committee. It offers dynamic advanced training courses consisting of daily lectures on emerging concepts, followed by extended discussion, laboratory research, technologically intense workshops, and informal seminars. Our similar training programs have recruited participants of whom 34% self-identify as African American/Black and 30% as Hispanic Americans; 66% are women, and 62% are from URM institutions. Six specific aims are proposed. Aim 1. Provide conceptual education and experimental training. Aim 2. Provide background information and self-reflective exercises and demonstrations to understand, appreciate, and address the historic and current underpinnings of inequities in the research workforce’s diversity and disparities in health care. Aim 3. Sponsor meaningful mentored research. Aim 4. Discuss career planning. Aim 5. Educate participants on the responsible conduct of research. Aim 6. Provide unbiased, quantitative, independent mechanisms to track trainees’ careers, comprehensively and longitudinally. The program’s name, FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY, acknowledges our hope that the COVID pandemic may soon recede significantly and our realization that other emerging, reemerging, and zoonotic diseases will arise that must be timely addressed. Overall, in conducting this program, we will continue to enhance and expand the research careers of the most promising scientists, with sensitivity to ensuring full diversity in the NIAID workforce.",,2026,MAGEE-WOMEN'S RES INST AND FOUNDATION,143420,Human Populations,Black | Other,Adults (18 and older),Unspecified,Other,Other,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +P23092,5R25AI164613-02,"Frontiers in Emerging, Reemerging and Zoonotic Diseases and Diversity (FrERZD2)","PROJECT SUMMARY Our nation is nearly paralyzed by the twin pandemics of COVID-19 and painful inequities in health outcomes among COVID-19 infected Americans of differing ethnicities. To help address these, we seek sponsorship to train the next generation of pandemic and emerging disease researchers in the FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY. FrERZD2 will launch and sustain three vital undertakings: sophisticated courses for skills development; relevant vital research experiences; and career mentoring activities. Responsive to PAR-20-289, it is designed for 16 trainees who are graduate and medical students, medical residents, postdoctoral fellows, and/or early-career faculty, and who also are US citizens or permanent residents. The week-long course will help to ensure that clinically active scientists (especially physicians) are able to obtain permission to participate. Too few laboratories are led by under-represented minority (URM) scientists, and not enough new URM trainees graduate. We seek 5 years of sponsorship to offer FrERZD2 courses at Morehouse School of Medicine (MSM), an HBCU, in 2021, 2023, and 2025 and Ponce Health Sciences University (PHSU), a Hispanic-Serving Institution, in 2022 and 2024. Under the overall directorship of Gerald Schatten from Pittsburgh, along with Jonathan Stiles at MSM, Idhaliz Flores from PHSU, and Calvin Simerly, also from Pittsburgh, FrERZD2 is overseen by an external scientific advisory committee. It offers dynamic advanced training courses consisting of daily lectures on emerging concepts, followed by extended discussion, laboratory research, technologically intense workshops, and informal seminars. Our similar training programs have recruited participants of whom 34% self-identify as African American/Black and 30% as Hispanic Americans; 66% are women, and 62% are from URM institutions. Six specific aims are proposed. Aim 1. Provide conceptual education and experimental training. Aim 2. Provide background information and self-reflective exercises and demonstrations to understand, appreciate, and address the historic and current underpinnings of inequities in the research workforce’s diversity and disparities in health care. Aim 3. Sponsor meaningful mentored research. Aim 4. Discuss career planning. Aim 5. Educate participants on the responsible conduct of research. Aim 6. Provide unbiased, quantitative, independent mechanisms to track trainees’ careers, comprehensively and longitudinally. The program’s name, FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY, acknowledges our hope that the COVID pandemic may soon recede significantly and our realization that other emerging, reemerging, and zoonotic diseases will arise that must be timely addressed. Overall, in conducting this program, we will continue to enhance and expand the research careers of the most promising scientists, with sensitivity to ensuring full diversity in the NIAID workforce.",,2026,MAGEE-WOMEN'S RES INST AND FOUNDATION,470138,Human Populations,Black | Other,Adults (18 and older),Unspecified,Other,Other,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +P23093,3UM1AI148684-03S2,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,11669860,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P23094,3UM1AI148684-03S1,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,38988,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P23095,3UM1AI148684-03S6,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,379095,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P23103,1K08NS119882-01A1,Viral Neurobiology in the Prenatal Brain,"ABSTRACT The prenatal brain is uniquely susceptible to viral infections. Such infections threaten 1 in 4 pregnancies and can cause severe neurodevelopmental disorders if not fetal demise. Different viruses lead to strikingly similar clinical outcomes due to overlapping viral neuropathology and the host’s common neuronal response. Such a reality calls for the development of urgently needed prenatal standards of care for prevention or treatment of virally induced brain injury. This need requires a much-deeper understanding of the corresponding neurobiology. A key regulator of the host’s common neuroviral response is the mechanistic target of rapamycin (mTOR) through essential roles in viral autophagy, which affect viral clearance and neuronal survival. There is unsettled controversy, however, about whether mTOR expression and viral autophagy are key defenses against, or requisites to, viral replication and neuronal injury. The PI has new preliminary data connecting mTOR with a novel neuroviral response gene, Hexosaminidase B (HEXB), and suggesting new cellular functions for this genetic complex in activating prenatal viral autophagy to prevent brain injury. Opening new research windows for therapeutic intervention, this sets the context for the proposed K08 study, which rigorously tests the guiding hypothesis that neurodevelopmental gene expression affects prenatal viral susceptibility toward brain injury. Purusing three integrated and synergistic aims in cellular, mouse, and human systems, the PI will investige how gene expression of mTOR and HEXB affects prenatal viral susceptibility and how it might be altered to prevent brain injury. First, human-derived organoids are used to study how expression of mTOR and HEXB affects viral clearance, neuronal survival, and up/downstream pathways (Aim 1). In parallel, this relationship is prenatally evaluated in vivo to determine its impact on postnatal development (Aim 2). Mirrored allelic series of mTOR and HEXB are genetically cross-titrated in these aims, which will shed light on a population genomic analysis to study the extent to which variants in these genes/pathways affect prenatal susceptibility to brain injury (Aim 3). This K08 grant combines research using synergistic/integrated systems with theoretical and technical training by seasoned mentors in neurobiology, neurovirology, and genomics at Children’s National Hospital and NINDS. The individually tailored career development plan uniquely positions the PI, a board-certified prenatal-neonatal critical care neurologist-scientist, to open multiple new research windows into the developing human brain by: (a) deepening our fundamental understanding of prenatal neurovirology and the crticial role of neuro- developmental genes (mTOR & HEXB), regulatory networks, and essential cellular functions; (b) examining genetic regulation of prenatal viral autophagy as a cornerstone for prenatal precision medicine; and (c) tapping into a robust neuroepidemiology research infrastructure (Consortium, CDC, NIH) to identify prenatal susceptibilities. The ultimate goal is to understand the connection between viral neurobiology and neuronal injury in the developing brain to optimize the neuropsychological life experience of future generations of children.",,2027,CHILDREN'S RESEARCH INSTITUTE,181260,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis",2022 +P23104,1R01HD105474-01A1,Jump Start+:COVID Support to improve resiliency and mitigate risks in childcare centers serving children from low-income ethnic minority backgrounds.,"Background. This is a Type 1 hybrid effectiveness-implementation trial studying the role of a community- based, childcare center-support system in improving resilience and mitigating the long-term impacts of the pandemic on child development. Public health disasters have disproportionate and long-term impacts on poor, disenfranchised communities. Miami-Dade County has one of the US's highest rates of chronic poverty, is minority majority, and has been an epicenter of the pandemic. COVID-19 is having psychosocial impacts on children that is producing anxiety, irritability, anger, and depression. Teachers in childcare centers continue to be overwhelmed by changing guidelines and how to address the downstream psychological effects children are experiencing. While numerous resources exist that can help childcare centers with disaster recovery, the information can be overwhelming and difficult to navigate, and research is yet to show the actual benefits of the resources. Approach. We will leverage our existing community-based intervention, Jump Start, with its extensive reach in Miami-Dade County, to childcare centers participating in the County’s Quality Improvement System. This system prioritizes children living in poverty who are at highest risk for problems. This study will be modeled on a successful Early Childhood Mental Health Consultation (ECMHC) intervention which utilizes mental health consultants to deliver a Jump Start+: COVID Support virtual toolkit to childcare centers via a Kubi robot. The toolkit is comprised of four strength-based strategies likely to be effective in improving resiliency following disasters: Safety Planning, Effective Communication, Adult Self-Care, and Trauma-Informed Behavior Support. We will use Reach, Effectiveness-Adoption, Implementation, Maintenance (RE-AIM) framework to guide the evaluation of our Type 1 hybrid design. Our first aim will utilize a cluster randomized trial to examine the effectiveness of Jump Start+: COVID Support on improving the psychosocial functioning of young children, as compared to an obesity-prevention intervention control group. Child development is the primary outcome, with children followed at 6, 12,18, and 24 months. The second aim will examine the mechanisms that contribute to effective teachers’ uptake of Jump Start+: COVID Support strategies on child outcomes. The third aim will explore implementation barriers/facilitators as well as potential societal contextual factors (e.g., vaccine uptake) to help centers serving disproportionately affected minority communities recover from and prepare for future crises. Impact. These aims meet a high-priority research area for NICHD because they address the social and environmental factors that can enhance children’s resilience. Employing a Type 1 hybrid design will inform the refinement and scaling of Jump Start+: COVID Support and generalize impacts to other childcare center interventions in the context of disasters. We have the potential to influence long-term trajectories of childcare center practices and child development which, in turn, can chart a course for future child health and well-being in the face of crises.",,2025,UNIVERSITY OF MIAMI SCHOOL OF MEDICINE,659883,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Social impacts | Policy research and interventions | Vaccine/Therapeutic/ treatment hesitancy,2022 +P23106,5R03AI151547-02,Screening antibodies for paper-based zika and dengue assays using microfluidic resistive pulse sensing,"PROJECT ABSTRACT Lateral flow assays are low-cost, paper based assays that can provide readouts within minutes. They have shown great promise as point of care rapid diagnostic tests (RDTs) for many hemorrhagic viral fevers such as dengue and zika because they are operable by non-experts, robust, and portable. A fluid is added to a test and wicks through, and if an antigen is present, a color appears at the test line due to the accumulation of gold nanoparticle (NP) antibody conjugates. While LFAs have proven utility in the field, they rely on antibody pairs specific for the biomarker of interest, so for every new disease a pair of antibodies must be determined. Arriving at a functional configuration of antibodies and NPs is labor intensive and expensive. In particular, each of the antibodies must be run in pairs and tested against each antigen in a paper strip format, as ELISA cannot predict sandwich immunoassay behavior. This presents major bottleneck in both time and required antibody samples, so any means to improve this process would significantly reduce the time and cost to produce RDTs for emerging outbreaks. Here, we will investigate the use of microfluidic resistive pulse sensing (MRPS) to help streamline the antibody screening method for a multiplexed dengue and zika test. MRPS is a highly sensitive technique that measures the size of a particle by its transport properties through a pore which has a voltage applied across it. MRPS requires very small sample volume and has the sensitivity to be able to measure when antigens bind to a NP-antibody complex. Thus, it has the potential to reduce sample requirements for screening and designing antibody pairs in an LFA. This could potentially reduce the amount of antibodies in immunoassay development, ultimately reducing both development costs and time. Benefits of the work will make immunoprobe design more efficient and would reduce the antibody amounts in screening for LFAs tests faster and at lower cost. Expediting immunoprobe optimization would also streamline assay development and improve rapid response to infectious disease outbreaks.",,2024,UNIVERSITY OF MASSACHUSETTS BOSTON,76250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23107,5R21AI146513-02,Determining the levels of resistance and patterns of cross-resistance for common kdr alleles in Aedes aegypti,"SUMMARY/ABSTRACT: Here we seek to understand the evolution of resistance to pyrethroid insecticides in Aedes aegypti, an important vector of human diseases such as dengue and Zika. Pyrethroid insecticides are widely used for control of adult Aedes, but resistance has evolved in many populations, representing global challenge for control of this vector and the diseases it transmits. Finding strategies for delaying the development of resistance by mosquito vectors to the few available insecticides is critical. To do so, it is essential to identify the level of resistance conferred, by common resistance alleles, to insecticides that target the voltage sensitive sodium channel (VSSC). This information will fill a critical data gap in our understanding of the evolution of resistance and will inform what options exist in populations where the different resistance alleles are found. Our long-term goals are to understand the importance of different Vssc alleles in the evolution of resistance so that this important process can be understood and the development of resistance can be delayed. Our short-term goal is to measure the level of resistance conferred by different Vssc mutations found in populations across the globe. To accomplish this goal we will pursue two specific aims. Aim 1. Isolate seven congenic (to the susceptible Liverpool strain) strains that have one of the common unstudied Vssc resistance alleles. Aim 2. Determine the level of resistance conferred by each Vssc allele to twenty insecticides that target the VSSC. This proposal fills an important data gap in our understanding of insecticide resistance in A. aegypti by quantitating the phenotype that the different alleles confer. In addition, our results will demonstrate what cross-resistance spectrum is conferred by each allele. This information will provide us with a vastly improved understanding of pyrethroid resistance in A. aegypti, and yield key information for resistance management in this important vector of human disease.",,2023,CORNELL UNIVERSITY,157000,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,,2020 +P23108,5R21AI149121-02,Identification of the pyrethroid resistance mutation on chromosome 1 in Aedes aegypti,"SUMMARY/ABSTRACT: Here we seek to understand the evolution of resistance to pyrethroid insecticides in Aedes aegypti, an important vector of human diseases such as dengue and Zika. Pyrethroid insecticides are widely used for control of adult Aedes, but resistance has evolved in many populations, representing a global challenge for control of this vector and the diseases it transmits. Finding strategies for delaying the development of resistance by mosquito vectors to the few available insecticides is critical. To do so, it is essential to identify the mutations responsible for resistance in order to design sensitive and precise monitoring programs, to understand the population genetics and the evolution of resistance, and to design effective countermeasures to slow the development of resistance. Our long-term goal is to develop the necessary technologies for monitoring resistance alleles so that this important evolutionary process can be studied and so that the development of resistance can be delayed. Our short-term goal is to determine the mutation responsible for the newly identified pyrethroid resistance locus on chromosome 1 in A. aegypti. To address our short-term goal, we will pursue two specific aims: Aim 1. Determining the resistance locus on chromosome 1 with high resolution. Aim 2. Evaluation of candidate genes at the resistance locus on chromosome 1 and validation of the mutation causing resistance. A substantial amount of preliminary data has been obtained in support of this proposal. In addition to the susceptible ROCK and well characterized SP strains, we have isolated two congenic resistant strains. The CKR strain contains the resistance factors from the SP strain introgressed into the background of the ROCK strain, and the KR strain contains only the kdr mutation in the background of ROCK. We have also conducted a transcriptomic (RNAseq) and proteomic analysis of these strains which will facilitate our selection of candidate genes at the resistance locus. These experiments will allow us to identify a new pyrethroid resistance mutation in A. aegypti and will give us preliminary information about its frequency in other populations of A. aegypti from across the globe. These data will provide new information about the similarities and differences that insecticide selection has had on geographically distant populations. Our results will form the basis for future studies of resistance monitoring and resistance management in this important vector of human disease.",,2023,CORNELL UNIVERSITY,196250,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,,2020 +P23111,5R01DC018403-02,The taste of ribonucleosides: The molecular and cellular basis underlying chemosensory detection of previously unknown macronutrients,"Insects are the most abundant class of animals, next to vertebrates. For example, the biomass of termites alone equals that of humans, the most abundant mammal. There are about 1 million named insect species and approximately another 5 million yet to be classified, compared to about 66,000 species of vertebrates. While overall beneficial to our ecosystem, some insects have considerable negative impact on human health. Disease vectors, mostly flies and mosquitoes, are major transmitter of microbes that cause devasting human diseases, including yellow fever, dengue, malaria and zika. These insect vectors kill close to a million people each year, sicken hundreds of millions more and incur billions of dollars annually in costs for treatment and lost productivity. Other insect species are agricultural pests and consume crops and fruits of cultivated plants, leading to famine in many parts of the world. In light of these facts, a better understanding of insect biology and behavior, in particular chemosensory behavior, is paramount for developing specific and effective strategies for population control of harmful pests. Drosophila melanogaster, with its array of experimental tools, is uniquely suited to uncover the basic principles underlying these behaviors. Like mammals and other insects, Drosophila depend on chemosensory systems to navigate their external world appropriately. The sense of taste is particularly important to identify food sources and avoid harmful chemicals. To assure that all essential food chemicals are consumed, insects have evolved appetitive taste receptors for the three major macronutrients, proteins, carbohydrates and fats. Intriguingly, Drosophila larvae, in contrast to adult flies, can also sense ribonucleosides and RNA in their food. These chemicals represent an essential resource required to support rapid growth and survival during the fast-growing larval stages. Larvae employ a small number of closely related taste receptors, the Gustatory Receptors (Grs) 28 to detect these chemicals. The Gr28 genes are among the most conserved insect taste receptor genes, homologs of which are found in all insect genomes, from flour beetles to honeybees to mosquitoes. These observations suggest that the Gr28 genes have a conserved role, namely to detect RNA and ribonucleosides in insects. Remarkably, some of the Gr28 genes have been implicated in temperature and light sensing, expanding their role to sensory pathways beyond taste. Thus, an in-depth understanding of the function of receptors for RNA and ribonucleosides is of considerable interest, especially because they are broadly conserved in diverse insect species, from disease vectors (mosquitoes and flies), to agricultural pests (beetles, grasshoppers) and ecologically beneficial pollinators (honeybees). Exploiting the ability of insects to sense RNA and ribonucleosides via specific taste receptors may provide new opportunities to develop strategies for control of harmful insects.",,2025,TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR,376797,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P23112,1UC2GM141586-01,Developing a Culture of Biomedical Research at the University of the Virgin Islands,"PROJECT SUMMARY This proposal will enhance and innovate the biomedical research infrastructure and training at the University of the Virgin Islands (UVI), the only higher educational institution in the US Virgin Islands (USVI). The overall objective of this proposal is to provide the highest level of sponsored program services for biomedical research by developing a culture of research through training, mentoring, collaboration and a strong infrastructure. UVI’s vision is to develop research resulting in an increase in the number of faculty conducting excellent externally funded biomedical research who will be able to mentor undergraduate students with potential for careers in science. There are several motivating factors for this project: (1) Diversity in the scientific workforce is key to the future biomedical discoveries that will improve the health of the Nation, and HBCUs such as UVI have an important role to play in training students who are underrepresented in science. (2) The USVI is a medically underserved area that experiences dramatic health disparities and emerging diseases including dengue, chikungunya, Zika, and the more recent coronavirus, which are important not only in the Caribbean but are also increasing on the US mainland. Little research on population health has been performed in the USVI and UVI continues to look at research in these areas. (3) Extensive undergraduate research experience is essential to prepare students for highly competitive doctoral programs. Although UVI has very successful programs that mentor undergraduates in research, there are many more UVI students interested in research experience than can be accommodated in externally funded research laboratories. (4) UVI has established a culture of innovation in its 2018-2023 Strategic Plan and through this research infrastructure and innovation is a primary focus area and is supported by the President and senior leadership. The UVI Institutional Development Plan (IDP) addresses barriers to research and informs the Specific Aims of this proposal: (1) Develop UVI’s research administration leadership and organization such that it is well-trained, resourced, and motivated to support a culture of research. (2) Develop research review and training programs for research faculty to increase the number and improve the competitiveness of proposal submissions (3) Increase mentorship and training opportunities for undergraduates in biomedical research by supporting faculty to receive external funding. This program is innovative because it will fully integrate the IDP for research within UVI’s 2018-2023 Strategic Plan, providing strong institution-wide commitment. Research and training innovations include targeted training initiatives covering the life cycle of research, increased outreach efforts, training and grant writing initiatives and focus groups of HBCU research administrators to overcome the barrier of geographic isolation. UVI’s logic model will be used to ensure that each activity will contribute to a sustainable vision for research and to developing a University-wide culture supporting research.",,2024,UNIVERSITY OF THE VIRGIN ISLANDS,273160,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research on Capacity Strengthening,Individual level capacity strengthening | Institutional level capacity strengthening,2021 +P23114,1R01AI165575-01,Opsins and TRP channels controlling sensation and behavior in Aedes aeygpti,"Abstract The mosquito Aedes aegypti spreads diseases such as dengue, Zika, yellow fever, and others that afflict >100 million people each year. These mosquitoes rely on multiple keen senses to locate human hosts for blood meals, and for finding conspecifics for mating. Currently, we have only a rudimentary understanding of the receptors that control these critical behaviors. The goal of the proposed research is to address this gap. The unifying theme of this proposal is to test the idea that opsins and TRP channels are two key classes of signaling proteins that have broad roles in sensation and in controlling behavior in Ae. aegypti. Rhodopsins are the founding G-protein coupled receptors (GPCRs). We recently discovered that opsins are multi-modal sensory receptors, challenging 100 years of dogma that they detect only light. To find humans, female Ae. aegypti integrate information from diverse stimuli, including CO2, visual cues, organic molecules, and convection heat from skin. We discovered another cue. Aim 1 builds on our preliminary data that Ae. aegypti use infrared (IR) radiation as an additional host stimulus. We outline experiments to reveal the roles of opsins and the TRPA1 channel in IR detection. We propose to identify the IR-sensing neurons that express the opsins and TRPA1, and to test a model to explain the role of opsins in IR sensation. To pursue this aim, we devised a highly effective assay for monitoring IR attraction and a new molecular genetic approach to bypass difficulties in combining multiple genetic elements. Aim 2 takes advantage of a mutation that we created in another TRP (TRPV-A), which renders males and females deaf. We will test the roles of hearing and TRPV-A in swarm formation, in mating, and in finding humans. Aim 2 will also build on the observations that male mating requires audition mediated by TRPV-A to devise a strategy to overcome a major impediment limiting the efficacy of the sterile insect technique (SIT). SIT is a promising strategy to suppress Ae. aegypti. It involves inundating a local population with sterile males, which then render females sterile upon mating. An obstacle to using SIT is that wild-type males outcompete sterile males. We propose that manipulation of the activity of the TRPV-A- expressing auditory neurons elevates sterile male mating success, and will thereby increase the efficacy of SIT in suppressing Ae. aegypti. Aim 3 concerns identifying the sensory receptors for repellents. We propose to test the idea that an opsin functions as a highly sensitive receptor for insect repellents. If confirmed by the proposed experiments, this would demonstrate that opsins comprise a new class of olfactory receptor. To accomplish our goals, we have developed an extensive repertoire of state-of-the-art approaches. These include new molecular genetic tools, a suite of behavioral assays, original video tracking software, and in vivo electrophysiological recordings. In summary, this project will reveal the roles of opsins and TRP channels in allowing mosquitoes to sense humans and conspecific mates. The insights gleaned from this work have exciting potential to lead to innovative strategies to control Ae. aegypti and reduce insect-borne disease.",,2026,UNIVERSITY OF CALIFORNIA SANTA BARBARA,542566,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P23115,1R01AI167300-01,Sublingual Supramolecular Vaccines and Immunotherapies,"Even when vaccines are rapidly developed and shown to be efficacious and safe, vaccination campaigns continue to be hampered by public hesitancy and by challenges distributing vaccines equitably around the globe. Vaccine hesitancy, where individuals refuse or delay vaccination, has been a persistent challenge, affecting a third to a quarter of individuals in the US and globally. Inequitably, it affects racial and ethnic minority communities particularly strongly, and in 2019 the World Health Organization named vaccine hesitancy as one of the top-ten threats to global health. Needle-based injections, which increase vaccine reactogenicity, are a significant driver of vaccine hesitancy. A second fundamental hurdle in equitable availability of vaccines involves the chain of distribution. Most vaccines must be transported and stored within a continuous cold-chain to prevent loss of potency, making global distribution challenging. In the face of these limitations, lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking vaccines, yet the issues of global distribution and patient acceptance are exponentially more challenging with repeated dosing. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered specifically for the sublingual route to provide for effective vaccination. The project aims to design a shelf- stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of- concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of immune responses remain to be articulated. Therefore the objective of the project is to articulate these design rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size, charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza, zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).",,2026,DUKE UNIVERSITY,435384,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Orthomyxoviridae,Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2021 +P23118,1R01AI155562-01A1,Comprehensive characterization of ancestral populations of the vector Aedes aegypti on Indian Ocean islands,"Project Summary/Abstract We have recently shown that the ancestors of all Aedes aegypti populations in both sub-Saharan Africa as well as around the world presently reside on islands in the Southwest Indian Ocean (SWIO) including Madagascar. These islands gave rise to continental African Ae. aegypti formosus no earlier than about 100,000 years ago. We propose multidisciplinary studies on SWIO populations of Ae. aegypti along with its close relatives, Ae. mascarensis and Ae. pia. This will include population genetics, phylogenetics/phylogeography, vector competence, blood meal analyses, and characterization of the virome of field-caught females. We address question such as: Are the ancestors that gave rise to Ae. aegypti s.s. capable of transmitting the same viruses that cause human diseases? Are these mosquitoes carrying the same viruses in the field and/or do they harbor novel undescribed arboviruses? What are the sources of their blood meals? Where do they breed? Population genetics and phylogenetic preliminary work have already identified candidates for new undescribed species and we suspect more cryptic taxa will be found. We propose to assemble complete genomes for the most informative populations/taxa that will allow comparative studies as well as inference of the ancestral genome of Ae. aegypti s.s., a fundamental resource for analysis of a plethora of genomics studies ongoing in laboratories around the world.",,2026,YALE UNIVERSITY,677919,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P23119,7K08AR070918-06,Contributions of IRF5 to Chikungunya Viral Arthritis,"Project Summary/Abstract The goal of this proposal is to develop the applicant into an independent investigator with a research program that examines the intersection of autoimmunity and antiviral immunity. The principal investigator (PI) previously received his PhD training in biochemistry and molecular biology while studying immune mechanisms of leukocyte trafficking at the Oklahoma Medical Research Foundation. As of 2015, the PI has completed his clinical training in internal medicine and rheumatology and is currently a post-doctoral fellow receiving formal training in immunology and virology at Washington University in Saint Louis. The mentor is Dr. Michael Diamond, Professor of Medicine at Washington University, Associate Director of the Center for Human Immunology and Immunotherapy Programs, and an established leader in the fields of innate immunity and viral pathogenesis. Dr. Diamond has over 270 publications with special expertise in studies of flaviviruses (e.g., West Nile, Dengue, and Zika viruses) and alphaviruses (e.g., Chikungunya virus). Dr. Diamond is an infectious disease specialist who provides a model of a successful physician-scientist to the applicant at Washington University, an internationally recognized premier academic institution. Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes acute and chronic synovitis in a distribution that mimics seronegative rheumatoid arthritis. Epidemiological studies conducted after the Reunion Island CHIKV outbreak in 2006 suggest that a majority of patients infected with CHIKV progress to chronic arthralgias and arthritis. At present, the role of specific interferon (IFN) stimulated genes and transcription factors during CHIKV infection is still being defined. IFN regulatory factor (IRF)5 is a transcription factor that is activated during viral infection and is known to upregulate expression of IFN stimulated genes, promote production of proinflammatory cytokines, and enhance apoptosis under certain conditions. Polymorphisms resulting in overexpression of human IRF5 are associated with the risk of developing systemic lupus erythematosus and rheumatoid arthritis. We hypothesize that the severity and duration of CHIKV arthritis also may be related to IRF5 polymorphisms that modulate the antiviral immune response during acute infection. Here, we propose to test the contribution of IRF5 expression globally and in specific cell types using an established mouse model of CHIKV arthritis. We also propose to generate knock-in mice that ectopically express IRF5 to test the effect of IRF5 gene dosage on the pathogenesis of CHIKV arthritis. Using these approaches, the applicant will gain expertise in immunology, virology, autoimmunity, and viral arthritis. This will establish a foundation for an independent research program that will study interactions between host genetic risk factors and pathogens that may act to trigger chronic rheumatologic diseases. Ã' ",,2022,UNIVERSITY OF PENNSYLVANIA,52250,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +P23120,5U01AI151378-02,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,2490957,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23121,1F31AI164939-01,Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence,"Bottom-up regulation and competition of Aedes aegypti (Diptera: Culicidae) larvae along an urbanization gradient in Puerto Rico: Effects on population performance and vector competence Aedes aegypti, is the primary vector of emerging arboviruses causing serious human illnesses including yellow fever, dengue, Zika, and chikungunya. Species population dynamics are related to urbanization and human density as larvae develop in man-made habitats and bloodfeed on humans. Previous studies have independently related urbanization parameters, detrital inputs, and larval competition to some aspects of Ae. aegypti life history (e.g., development time, biomass, fecundity) and vector competence. However, no study has determined how urbanization can influence these ecological interactions in larval habitats, the effect that this can have on Ae. aegypti performance across life stages, generations, and vector competence, nor have used a nutrient stoichiometry approach to do so. Urbanization changes could translate to changes in detritus availability and species competition in larval habitats along a gradient of urbanization which could in turn, influence the susceptibility of Ae. aegypti to dengue infection. The first objective of this proposal is to determine the influence of urbanization on Ae. aegypti larval bottom-up effects and competition in Puerto Rico. The second and third objectives are to assess the influence of urbanization related-detrital inputs and Aedes sp. competition on the species life history across generations and vector competence, respectively. Preliminary data suggests that plant detritus biomass and composition have a significant effect on Ae. aegypti larval and adult biomass. In addition, container water nitrogen (%N) significantly increases with urbanization, that water Carbon:Nitrogen (C:N) is significantly higher in suburban containers, and C:N exhibits a significant relationship with Ae. aegypti larval biomass. The overall hypothesis of this proposal is that urbanization influences detrital inputs and competition in Ae. aegypti larval habitats and that this variation will affect species performance (survival, development rate, and biomass) and dengue vector competence. A combination of field sampling and laboratory experiments will be used to answer the objectives. Sixty larval containers will be sampled across a gradient of urbanization in San Juan, Puerto Rico following a stratified random sampling method with three strata (urban density): low, medium, and high. Incubated containers will simulate larval conditions of each strata with combinations of detrital inputs and species intraspecific and interspecific competition. Aedes aegypti females will be infected with a dengue blood meal to determine virus dissemination and transmission rates. Nutrient analysis (i.e., %C %N, C:N) will be performed on container water, detritus, larvae, and adults from field and laboratory experiments. The results of this research have relevance to vector ecology, vector control strategies, arbovirus diseases, and public health.",,2025,UNIVERSITY OF SOUTHERN MISSISSIPPI,34293,Human Populations | Disease Vectors,Unspecified | Not applicable,Adults (18 and older) | Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2022 +P23123,5U01CK000580-02,PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ARBOVIRUSES (PRESCA) PROGRAM,"PROJECT SUMMARY The impact of infections transmitted by mosquitoes is global. Arboviral diseases such as dengue, chikungunya, and Zika are a significant health concern due to the expanding geographical range of many mosquito species. Emphasis on disease surveillance systems is central to evaluate the effectiveness of primary and secondary dengue prevention methods and strategies, including the introduction of dengue vaccines and new vector control methods. In the current application, the study team will address specific and fundamental gaps in the diagnosis and clinical management of dengue and other acute febrile illnesses (AFI); ultimately, evaluating the efficacy of vector control strategies in reducing the incidence of arbovirus infection through a combination of both clinic- and community-based surveillance systems. The study team’s long-term goal is to mitigate arboviral and other AFI disease burdens by improving diagnosis, clinical management, and prevention strategies. The study’s central hypothesis is that arbovirus infections and AFI disease surveillance, through the continuation of SEDSS and COPA, will promote evidence-driven public health policy decisions and reduce the burden of disease. The rationale for the current study is that understanding the etiology, epidemiology, and severity of arboviral diseases will allow the United States to be better prepared and respond to critical vector- borne disease outbreaks. The study team will test the central hypothesis by pursuing two specific aims: 1) Explore the natural history of dengue and arboviral infections and other acute febrile illnesses in their differential diagnosis to understand their epidemiology, spectrum of disease, and outcomes to provide recommendations for diagnosis and clinical management, and; 2) Define the correlates of risk and protection of arbovirus transmission in the setting of vector-reduction strategies. Under Specific Aim 1, the team will strengthen hospital surveillance of acute febrile illness (AFI) and maintain an AFI platform for conducting clinical research. For Specific Aim 2, the team will maintain a community-based cohort to assess the incidence and prevalence of arboviral infection, as well as, evaluate the incidence, prevalence, and etiology of other AFIs in selected communities. Central to both aims is the establishment of a data management system and the continuation of strengthening collaborations with the local government, community leaders, and other stakeholders to ensure continuity of the established program. The proposed research is significant because it is expected to deliver robust and broad knowledge regarding the epidemiologic patterns of common arboviral diseases in the context of other AFI of the present and those that may emerge in the geographical setting. Such results provide evidence- based responses to critical questions regarding dengue (and other arboviruses) diagnosis, immune response, and clinical management. Also, the community-based system will be central to evaluate the efficacy of vector control strategies in reducing the incidence of arboviral diseases in humans and assessing its potential use among other populations.",,2024,PONCE SCHOOL OF MEDICINE,2750000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P23127,1R01AI155512-01A1,Regulation of RIG-I signaling and viral immune evasion by ufmylation,"ABSTRACT Type I and III interferons (IFN) restrict RNA virus infection. Infected cells produce IFN through signaling activated by pattern recognition receptors such as RIG-I. Both RIG-I and downstream signaling must be highly coordinated for efficient antiviral responses. As such, these processes are regulated by several post-translational modifications (PTMs). These PTMs are essential for both the activation and eventual termination of RIG-I- signaling. While RIG-I-signaling is coordinated by ubiquitination and phosphorylation, the mechanisms by which other PTMs, such as ubiquitin-like modifiers, may regulate RIG-I-signaling are largely unknown. Our preliminary data reveal that the ubiquitin-like modifier called ufmylation regulates multiple proteins involved in RIG-I signaling for optimal IFN induction in response to viral infection. Further, our data suggest that ufmylation is utilized by viruses to evade the host intracellular innate immune response. Therefore, the goal of this proposal is to determine how ufmylation regulates the intracellular innate immune response to virus infection and viral evasion. Based on our preliminary data, the central hypothesis is that ufmylation modulates the function of host and viral proteins to regulate antiviral innate immunity and viral evasion. Guided by our preliminary data, this hypothesis will be tested by pursuing the following three specific aims: 1) Define how UFL1, the ufmylation E3 ligase, promotes the activation of RIG-I; 2) Understand the molecular mechanism by which ufmylation of a key protein in the RIG-I signaling pathway downregulates its function and signaling; 3) Determine how dengue virus co-opts the ufmylation conjugation system for immune evasion. In Aim 1, the molecular mechanisms by which UFL1 induces the activation of RIG-I in response to RNA virus sensing will be defined. In Aim 2, the mechanism and dynamics of how ufmylation regulates the function of a signaling protein in RIG-I pathway will be determined. In Aim 3, the function by which ufmylation of a DENV protein promotes DENV immune evasion, both in human cell lines and in primary cells, will be determined. Taken together, the work proposed in this application will be significant and innovative because it will attribute a novel immune regulatory function to ufmylation, contribute to our understanding of its basic functions, and uncover a novel control (ufmylation) of antiviral innate immunity. Additionally, this work will provide understanding of a host-directed process that is utilized by viruses for immune evasion to facilitate viral replication. Overall, this work will define a new PTM that coordinates the RIG-I signaling pathway, which will improve our knowledge of both antiviral immunity and regulation of innate immune pathways that will lead to increased understanding of the mechanistic causes of dysregulated IFN that can ultimately result in autoimmune disease. It will also define a new mechanism of immune evasion by flaviviruses that will have implications for therapeutic and vaccine strategies to limit their infection.",,2026,DUKE UNIVERSITY,461559,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P23134,3UM1AI148684-02S4,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) - Momi-Vax DMID #21-0004 {Supplement #6},"IDCRC LG Project Summary/Abstract: This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the LG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG's experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the LG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG's experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG's decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The LG and the institutions represented are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2024,EMORY UNIVERSITY,2253969,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P23135,3UM1AI148684-02S1,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2022,EMORY UNIVERSITY,933971,Unspecified,Not applicable,Unspecified,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P23136,3UM1AI148684-02S2,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) - Moderna Boost {Supplement #5},"IDCRC LG Project Summary/Abstract: This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the LG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG's experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the LG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG's experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG's decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The LG and the institutions represented are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2022,EMORY UNIVERSITY,472962,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P23137,1R25AI164613-01,"Frontiers in Emerging, Reemerging and Zoonotic Diseases and Diversity (FrERZD2)","PROJECT SUMMARY Our nation is nearly paralyzed by the twin pandemics of COVID-19 and painful inequities in health outcomes among COVID-19 infected Americans of differing ethnicities. To help address these, we seek sponsorship to train the next generation of pandemic and emerging disease researchers in the FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY. FrERZD2 will launch and sustain three vital undertakings: sophisticated courses for skills development; relevant vital research experiences; and career mentoring activities. Responsive to PAR-20-289, it is designed for 16 trainees who are graduate and medical students, medical residents, postdoctoral fellows, and/or early-career faculty, and who also are US citizens or permanent residents. The week-long course will help to ensure that clinically active scientists (especially physicians) are able to obtain permission to participate. Too few laboratories are led by under-represented minority (URM) scientists, and not enough new URM trainees graduate. We seek 5 years of sponsorship to offer FrERZD2 courses at Morehouse School of Medicine (MSM), an HBCU, in 2021, 2023, and 2025 and Ponce Health Sciences University (PHSU), a Hispanic-Serving Institution, in 2022 and 2024. Under the overall directorship of Gerald Schatten from Pittsburgh, along with Jonathan Stiles at MSM, Idhaliz Flores from PHSU, and Calvin Simerly, also from Pittsburgh, FrERZD2 is overseen by an external scientific advisory committee. It offers dynamic advanced training courses consisting of daily lectures on emerging concepts, followed by extended discussion, laboratory research, technologically intense workshops, and informal seminars. Our similar training programs have recruited participants of whom 34% self-identify as African American/Black and 30% as Hispanic Americans; 66% are women, and 62% are from URM institutions. Six specific aims are proposed. Aim 1. Provide conceptual education and experimental training. Aim 2. Provide background information and self-reflective exercises and demonstrations to understand, appreciate, and address the historic and current underpinnings of inequities in the research workforce’s diversity and disparities in health care. Aim 3. Sponsor meaningful mentored research. Aim 4. Discuss career planning. Aim 5. Educate participants on the responsible conduct of research. Aim 6. Provide unbiased, quantitative, independent mechanisms to track trainees’ careers, comprehensively and longitudinally. The program’s name, FRONTIERS IN EMERGING, RE-EMERGING AND ZOONOTIC DISEASES AND DIVERSITY, acknowledges our hope that the COVID pandemic may soon recede significantly and our realization that other emerging, reemerging, and zoonotic diseases will arise that must be timely addressed. Overall, in conducting this program, we will continue to enhance and expand the research careers of the most promising scientists, with sensitivity to ensuring full diversity in the NIAID workforce.",,2026,MAGEE-WOMEN'S RES INST AND FOUNDATION,352950,Human Populations,Black | Other,Adults (18 and older),Unspecified,Other,Other,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities",2021 +P23138,3UM1AI148684-02S3,"Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) â€Â"" Gritstone, Variant, & Pediatric Vaccine Trials","IDCRC LG Project Summary/Abstract: This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the LG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG's experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the LG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG's experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG's decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The LG and the institutions represented are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2023,EMORY UNIVERSITY,2577219,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P23139,3UM1AI148684-02S5,"Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG) â€Â"" Mix & Match DMID #21-0012 {Supplement #7}","IDCRC LG Project Summary/Abstract: This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the LG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG's experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the LG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG's experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG's decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The LG and the institutions represented are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2025,EMORY UNIVERSITY,3094264,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2021 +P23145,1R03AI151547-01,Screening antibodies for paper-based zika and dengue assays using microfluidic resistive pulse sensing,"PROJECT ABSTRACT Lateral flow assays are low-cost, paper based assays that can provide readouts within minutes. They have shown great promise as point of care rapid diagnostic tests (RDTs) for many hemorrhagic viral fevers such as dengue and zika because they are operable by non-experts, robust, and portable. A fluid is added to a test and wicks through, and if an antigen is present, a color appears at the test line due to the accumulation of gold nanoparticle (NP) antibody conjugates. While LFAs have proven utility in the field, they rely on antibody pairs specific for the biomarker of interest, so for every new disease a pair of antibodies must be determined. Arriving at a functional configuration of antibodies and NPs is labor intensive and expensive. In particular, each of the antibodies must be run in pairs and tested against each antigen in a paper strip format, as ELISA cannot predict sandwich immunoassay behavior. This presents major bottleneck in both time and required antibody samples, so any means to improve this process would significantly reduce the time and cost to produce RDTs for emerging outbreaks. Here, we will investigate the use of microfluidic resistive pulse sensing (MRPS) to help streamline the antibody screening method for a multiplexed dengue and zika test. MRPS is a highly sensitive technique that measures the size of a particle by its transport properties through a pore which has a voltage applied across it. MRPS requires very small sample volume and has the sensitivity to be able to measure when antigens bind to a NP-antibody complex. Thus, it has the potential to reduce sample requirements for screening and designing antibody pairs in an LFA. This could potentially reduce the amount of antibodies in immunoassay development, ultimately reducing both development costs and time. Benefits of the work will make immunoprobe design more efficient and would reduce the antibody amounts in screening for LFAs tests faster and at lower cost. Expediting immunoprobe optimization would also streamline assay development and improve rapid response to infectious disease outbreaks.",,2022,UNIVERSITY OF MASSACHUSETTS BOSTON,76250,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23146,1R21AI146513-01A1,Determining the levels of resistance and patterns of cross-resistance for common kdr alleles in Aedes aegypti,"SUMMARY/ABSTRACT: Here we seek to understand the evolution of resistance to pyrethroid insecticides in Aedes aegypti, an important vector of human diseases such as dengue and Zika. Pyrethroid insecticides are widely used for control of adult Aedes, but resistance has evolved in many populations, representing global challenge for control of this vector and the diseases it transmits. Finding strategies for delaying the development of resistance by mosquito vectors to the few available insecticides is critical. To do so, it is essential to identify the level of resistance conferred, by common resistance alleles, to insecticides that target the voltage sensitive sodium channel (VSSC). This information will fill a critical data gap in our understanding of the evolution of resistance and will inform what options exist in populations where the different resistance alleles are found. Our long-term goals are to understand the importance of different Vssc alleles in the evolution of resistance so that this important process can be understood and the development of resistance can be delayed. Our short-term goal is to measure the level of resistance conferred by different Vssc mutations found in populations across the globe. To accomplish this goal we will pursue two specific aims. Aim 1. Isolate seven congenic (to the susceptible Liverpool strain) strains that have one of the common unstudied Vssc resistance alleles. Aim 2. Determine the level of resistance conferred by each Vssc allele to twenty insecticides that target the VSSC. This proposal fills an important data gap in our understanding of insecticide resistance in A. aegypti by quantitating the phenotype that the different alleles confer. In addition, our results will demonstrate what cross-resistance spectrum is conferred by each allele. This information will provide us with a vastly improved understanding of pyrethroid resistance in A. aegypti, and yield key information for resistance management in this important vector of human disease.",,2022,CORNELL UNIVERSITY,266200,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,,2020 +P23147,1R43AI155191-01,Integration of Wolbachia-based Incompatible Insect Technique (IIT) and Auto-Dissemination Augmented by Males (ADAM) for mosquito vector control,"Abstract In the absence of effective, approved vaccines or therapeutic measures against dengue, Zika and other mosquito borne pathogens, public health efforts must focus on the control of mosquito vectors that are required for transmission. Unfortunately, effective control measures are not available against invasive mosquito species like Aedes aegypti and Aedes albopictus, due in part to problems resulting from their cryptic behaviour. Specifically, Aedes mosquitoes breed in hidden/inaccessible sites that are sheltered from existing control methods, e.g., truck and aerial spraying. Autocidal technologies use the insect itself as a self-delivering control tool. As an example, the Sterile Insect Technique (SIT) has been used successfully against multiple agricultural pests, including large scale elimination from the North American continent (e.g., Screwworm; Cochliomyia hominivorax). However, despite years of effort, SIT has not proven effective against mosquitoes. Through previous SBIR-funded research, MosquitoMate has developed two autocidal methods against Ae. aegypti and Ae. albopictus mosquitoes, including: 1) Incompatible Insect Technique (IIT) that uses a naturally occurring bacterium (Wolbachia) to sterilize populations, and 2) Auto-Dissemination Augmented by Males (ADAM) that uses males as vehicles to spread a potent insecticide. To date, the USA Environmental Protection Agency (EPA) has instructed MosquitoMate to keep the IIT and ADAM approaches separate. In the work proposed here, MosquitoMate will develop data that the EPA can consider for the integration of the two approaches. If awarded, the resulting research will examine parameters critical to the EPA’s efficacy and risk assessments, including potential: 1) PPF effects on Wolbachia-induced sterility, 2) PPF effects on male mosquito performance (e.g., ‘boosting’ of male competitiveness), and 3) PPF effects on adult female mosquito fecundity and fitness. The resulting data will be communicated to the EPA, including a pre-registration meeting to identify requirements leading to FIFRA Section 3 EPA pesticide registration for the combined IIT/ADAM approach. Market potential exists at the local, corporate, government and area wide control levels for the control of invasive, medically important mosquito species. MosquitoMate has an exclusive license for the patented Wolbachia technology and additional patents on the ADAM technology.",,2022,"MOSQUITOMATE, INC.",193500,Disease Vectors | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector control strategies,2020 +P23152,1R21HL150032-01,"MIRAGES: Metabolic Investigation of Red blood cells as a function of Aging, Genetics, Environment, and Storage","PROJECT SUMMARY Red blood cells are the most abundant cell type in the human body, accounting for 25 out of 30 trillion total human cells in an adult individual. During their 120-day life span in the circulatory system, red blood cells play a vital role in the transport of oxygen and its delivery to tissues, a function that is finely tuned by red blood cell metabolism. By leveraging novel technology generated in the lab (“high-throughput metabolomics”) and an international network of ~45 collaborators (providing a total of ~20,000 samples from research and clinical cohort studies), we will investigate how factors such as aging, genetics, environment and storage impact red blood cell metabolism and, in so doing, influence tissue oxygenation and systems physiology in health and disease. At completion of this hypothesis-generating project, we will have defined how and to what extent red blood cell metabolism is modulated as a function of: (i) Aging, from intra-uterine to elderly life, from erythropoiesis to senescent red blood cells; (ii) Genetics, including sex (chromosome X/Y), ethnicity, species (by investigating red cells from zoo animals and research animal models) â€Â"" aneuploidy (Down syndrome) or mutations that impact the activity of enzymes involved in red cell metabolism (including glucose 6-phosphate dehydrogenase deficiency â€Â"" the most common enzymopathy in humans that impacts ~400 million people) and oxygen transport, such as Sickle Cell Disease, beta-thalassemia; (iii) Environment, including diet, iron availability, exercise, hormonal therapy in subjects undergoing sex exchange therapy, microbiome, infections (either bacterial or viral infections â€Â"" including malaria, Zika, Dengue, Chikungunya virus), conditions related to hypoxia (such as high-altitude, respiratory diseases, ischemic or hemorrhagic shock, cancer, radio and chemotherapy) and drugs; (iv) Storage, in the largest available clinical cohort (13,800 donors) and animal models. The project will pave the way for the generation of RBC Atlas, an online repository for the dissemination of metabolic data from red blood cell-related studies, a critical step towards Personalized Transfusion Medicine. Finally, we will investigate mechanisms of metabolic regulation mediated by the “AE1-Hb switch”, a phenomenon that involves the most abundant red blood cell proteins in the cytosol and membrane, hemoglobin and band 3 (AE1), respectively. Knowledge and technology developed in this study will inform our understanding of red cell metabolic regulation in health and disease, as well as our capacity to manipulate it for diagnostic and therapeutic purposes. Translation of expected findings will impact diverse endeavors, from clinical biochemistry to personalized transfusion medicine, from hematology to veterinary medicine, from pulmonology to virology, from sports physiology to cancer medicine.",,2022,UNIVERSITY OF COLORADO DENVER,187669,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +P23154,1U01DP006623-01,Maryland Pregnancy Risk Assessment Monitoring System (PRAMS),"Pregnancy Risk Assessment Monitoring System (PRAMS) in Maryland Executive Summary, July 2020 Background-The Maternal and Child Health Bureau and the Vital Statistics Administration have worked jointly to implement the Maryland PRAMS project since 2000 through a cooperative agreement with the Centers for Disease Control and Prevention (CDC). PRAMS surveys mothers 2-9 months after delivery about factors before, during, and shortly after pregnancy that may have an impact on pregnancy outcome. The program has also proven its capacity to implement survey supplements on emerging issues including the influenza vaccine, Zika, disability, and opioid use. The Maryland PRAMS survey booklet is sent monthly to a sample of new mothers along with an incentive (manicure file). The survey questionnaire, as well as other PRAMS materials, is available in both English and Spanish. Each mother is sent up to three surveys followed by a telephone interview if no written surveys have been returned. A $100 gift card is given out monthly to a mother chosen randomly who has completed the mail or phone survey. Maryland currently utilizes a stratified random sample based on infant birth weight (over-selecting mothers who have delivered a low birth weight infant under <2500 grams). Program Features-Maryland PRAMS data are analyzed annually and currently include reports from 2001 to 2017 birth years. Focus Briefs on various topics are posted on the PRAMS website at www.marylandprams.org. Human Subjects Training occurs annually for all PRAMS staff and was last completed in July 2020. Number of Mothers Served-Approximately 2,000 new mothers are surveyed annually. As of June 2020, 44,714 new mothers in Maryland have been mailed the PRAMS survey since its inception. Annual weighted response rates from 2001-2017 births have met or exceeded the threshold. Budget-Maryland PRAMS is currently funded at $172,500 annually ($157,500 in core funding and $15,000 in supplemental disability funding). We are currently in year five of a five year cycle. This competitive application is for year one of the next 5 year grant cycle. We will be requesting the ceiling award amount of $175,000.",,2026,MARYLAND STATE DEPARTMENT OF HEALTH,160020,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P23156,1U01CK000580-01,PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ARBOVIRUSES (PRESCA) PROGRAM,"PROJECT SUMMARY The impact of infections transmitted by mosquitoes is global. Arboviral diseases such as dengue, chikungunya, and Zika are a significant health concern due to the expanding geographical range of many mosquito species. Emphasis on disease surveillance systems is central to evaluate the effectiveness of primary and secondary dengue prevention methods and strategies, including the introduction of dengue vaccines and new vector control methods. In the current application, the study team will address specific and fundamental gaps in the diagnosis and clinical management of dengue and other acute febrile illnesses (AFI); ultimately, evaluating the efficacy of vector control strategies in reducing the incidence of arbovirus infection through a combination of both clinic- and community-based surveillance systems. The study team’s long-term goal is to mitigate arboviral and other AFI disease burdens by improving diagnosis, clinical management, and prevention strategies. The study’s central hypothesis is that arbovirus infections and AFI disease surveillance, through the continuation of SEDSS and COPA, will promote evidence-driven public health policy decisions and reduce the burden of disease. The rationale for the current study is that understanding the etiology, epidemiology, and severity of arboviral diseases will allow the United States to be better prepared and respond to critical vector- borne disease outbreaks. The study team will test the central hypothesis by pursuing two specific aims: 1) Explore the natural history of dengue and arboviral infections and other acute febrile illnesses in their differential diagnosis to understand their epidemiology, spectrum of disease, and outcomes to provide recommendations for diagnosis and clinical management, and; 2) Define the correlates of risk and protection of arbovirus transmission in the setting of vector-reduction strategies. Under Specific Aim 1, the team will strengthen hospital surveillance of acute febrile illness (AFI) and maintain an AFI platform for conducting clinical research. For Specific Aim 2, the team will maintain a community-based cohort to assess the incidence and prevalence of arboviral infection, as well as, evaluate the incidence, prevalence, and etiology of other AFIs in selected communities. Central to both aims is the establishment of a data management system and the continuation of strengthening collaborations with the local government, community leaders, and other stakeholders to ensure continuity of the established program. The proposed research is significant because it is expected to deliver robust and broad knowledge regarding the epidemiologic patterns of common arboviral diseases in the context of other AFI of the present and those that may emerge in the geographical setting. Such results provide evidence- based responses to critical questions regarding dengue (and other arboviruses) diagnosis, immune response, and clinical management. Also, the community-based system will be central to evaluate the efficacy of vector control strategies in reducing the incidence of arboviral diseases in humans and assessing its potential use among other populations.",,2025,PONCE SCHOOL OF MEDICINE,1342000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Flaviviridae,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P23157,1U01AI151378-01,Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC),"PROJECT SUMMARY/ABSTRACT Emerging and re-emerging infectious disease (EID) outbreaks that are occurring with increasing frequency in high-risk areas in South/Central America, West/Central Africa, and Southeast Asia are a threat to the United States. Documented gaps in research infrastructure limit the capacity to rapidly respond to these outbreaks. To address this challenge, the National Institute of Allergy and Infectious Diseases (NIAID) is establishing the Emerging Infectious Disease Research Centers Network (EIDRC-Net) to improve knowledge of EIDs; leverage existing NIAID international efforts; and develop the capacity to mount effective, flexible, and rapid outbreak research responses. RTI International and Duke University propose to establish the EIDRC Coordination Center (EIDRC CC). The RTI-Duke CC will support the EIDRC-Net, which will comprise the EIDRCs, research sites, the CC, and NIAID by realizing the following aims: (1) enhance EIDRC coordination and collaboration by providing administrative, communications, logistical, and operational support; (2) amplify NIAID's capabilities and reach by coordinating and supporting a sustainable, scalable, and adaptable research infrastructure to optimize resources and knowledge sharing during inter-outbreak periods and to respond rapidly and effectively during outbreaks; (3) ensure quality and consistency of study data by using rigorous data and specimen management systems with built-in data quality assurance; (4) ensure quality of biospecimens, assays, and reagents through harmonization of standard operating procedures across EIDRC-Net sites and ongoing audit of cross-network procedures; and (5) develop the next generation of investigators and in-country scientists by establishing a pilot research program that identifies, funds, and mentors high-quality EIDRC applicants. By successfully accomplishing our five specific aims, the RTI-Duke team will shift the outbreak research response paradigm by establishing scalable systems, processes, and resources that not only provide the necessary infrastructure to facilitate EIDRC-Net performance and carry out CC core functions during inter-outbreak periods, but also can be enhanced and expanded to bolster CC research surge response activities during outbreaks. The EIDRC CC team will be co-led by multiple Principal Investigators Donald Brambilla, PhD (RTI), a biostatistician with advanced training in biology and an experienced CC leader, and Michael Anthony (Tony) Moody, MD (Duke), a pediatric infectious disease specialist and Chief Medical Officer of the Duke Human Vaccine Institute. Together they bring extensive scientific expertise, leadership, administrative experience, and international research expertise, including in geographic locations most relevant to the study of EIDs. This partnership also leverages the operational efficiency of RTI, a large nonprofit research organization with regional and project offices in over 75 countries, with the scientific rigor of Duke University, a premier university known for its cutting-edge medical research and home to a state-of-the-art, NIAID-funded Regional Biocontainment Laboratory.",,2025,RESEARCH TRIANGLE INSTITUTE,1514714,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23159,1R21DC018497-01,Towards molecular mechanisms of invertebrate Gustatory Receptors,"PROJECT SUMMARY Invertebrate Gustatory Receptors (GRs) are a large and evolutionarily diverse family of sensory receptors known to play important roles in invertebrate taste, smell and thermotransduction. Given the importance of these sensory modalities in host-seeking behavior in important humand disease vectors like mosquitoes, GR family members serve as potentially powerful targets for vector control agents. However, little is known about GR structure and function. We propose a physiological and biochemical analysis of members of two GR subfamilies: Gr43a and Gr28bD. These initial studies will serve as a precursor for a subsequent R01 to carry out structural and functional analyses of these GRs. We propose to achieve these goals in two aims: Aim #1: Identify and physiologically characterize multiple orthologs of Gr43a and Gr28bD. Unlike most GRs, Gr43a and Gr28bD orthologs can be functionally characterized in heterologous cells. In aim 1.a., we will express orthologs of these GRs from additional insect species, including disease vectors and extremophiles, in heterologous cells and characterize their physiological properties. This will enable a comparative analysis of sequence and function among each receptor class. Aim #2: Biochemically characterize multiple Gr43a and Gr28bD orthologs. We find Gr43a and Gr28bD orthologs can be partially purified from heterologous cells. In aim 2, we will expand this approach to incorporate additional orthologs characterized in aim 1 and optimize our purification protocol and explore key properties including oligomeric state and thermal stability in various membrane mimics. This will provide important biochemical information about GR complexes and identify orthologs best suited for subsequent structural analysis. The physiological characterization of multiple Gr43a and Gr28bD orthologs will enable direct examination of evolutionary variation and conservation in GR family function. The expression and purification of multiple family members will provide multiple candidates for biochemistry and structural determination, maximizing the likelihood of success of subsequent GR structural determinations.",,2021,BRANDEIS UNIVERSITY,255251,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Animal and environmental research and research on diseases vectors,Vector biology,2020 +P23166,1R15AI146982-01A1,"Development of a novel and broadly applicable thermostable bacteriophage VLPs platforms for vaccine design, drug delivery, and imaging","PROJECT SUMMARY Virus-like particles (VLPs) resemble - in size, structure, and immunogenicity - the virus from which the coat or envelope protein(s) are derived from except for the fact they lack a viral genome; VLPs are non-infectious and are safe. These features have been exploited to develop VLP-based vaccines against human papillomaviruses and hepatitis B virus; furthermore, coat proteins from ~70 viruses are currently being explored to develop VLP- based vaccines against these viruses. VLPs from some of these viruses have also been used as display platforms to develop chimeric VLPs displaying heterologous peptides from other infectious agents, tumor- associated antigens and other metabolic diseases. The goal of these chimeric VLPs is to induce antibodies against the heterologous antigen displayed on the platforms and not the platforms. In addition to serving as display platforms, VLPs have also been used for targeted delivery of drugs or cargo to specific cancer cells. While the candidate VLPs-based vaccines displaying heterologous peptides are very effective in animal studies, in the majority of studies, VLPs platforms (including adenoviral VLPs or dodecahedron) are derived from viruses that infect humans and in some cases, studies used VLPs platforms that had previously been used to immunize the general population; a good example is HBV vaccine, with a global infant vaccination coverage of 84% in 2015. Vaccines based on some of these platforms, with pre-existing antibodies in the general population, are likely to be less immunogenic in humans. Additionally, there is a limitation on the size of heterologous antigens that can be genetically displayed on some VLPs platforms making it challenging to display a single peptide with multiple epitopes on the same VLPs. Moreover, most of the VLPs platforms are temperature-sensitive making them less suitable in developing countries with poor refrigeration facilities. In this proposal, the PI will develop and characterize novel thermostable bacteriophage VLPs platforms using coat proteins from thermophilic viruses P23-77 and ΦIN93. P23-77 and ΦIN93 was isolated from bacteria that grow at 70-75 Ã'°C. Thus VLPs derived from these viruses are likely to be stable at room temperature (RT) or above RT. Additional benefit of these VLPs platforms is that because these viruses do not infect humans, the human population lacks pre-existing neutralizing antibodies against the VLPs platforms; thus, the immunogenicity of the platforms cannot be compromised by pre-existing antibodies. Also, many surface- exposed loops on the capsid may tolerate larger insertions of heterologous antigens. The PI will co-express three coat proteins from P23-77 and two coat proteins from ΦIN93. The PI will assess whether the coat proteins can assemble into VLPs, if they VLPs are thermostable, can tolerate heterologous peptide insertions from human papillomaviruses, and if VLPs are immunogenic in comparison to the virus(es).",,2020,MICHIGAN TECHNOLOGICAL UNIVERSITY,54367,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P23168,3UM1AI148684-01S1,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2021,EMORY UNIVERSITY,979886,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P23169,3UM1AI148684-01S2,Leadership Group for the Infectious Diseases Clinical Research Consortium (IDCRCLG),"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC.",,2022,EMORY UNIVERSITY,2492267,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Other | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P23175,3UM1AI148689-01S2,Vaccine Treatment Evaluation Units: Infectious Diseases Clinical ResearchConsortium,"Project Summary The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. Under the current VTEU contract, CVD was awarded over 18 Task Orders, enrolled over 700 participants, and successfully collaborated with national and international sites. With this application for renewed funding, CVD has again assembled an expert and accomplished investigative team with complementary skill sets in all areas necessary to address the NIAID priority areas. Our technical capacities are complemented by effective and proven leadership of large contracts and initiatives; extensive clinical research experience, including performance of clinical trials in all phases of development and human challenge studies; in-depth subject matter expertise in NIAID priority areas; an accomplished record in training fellows and junior faculty in clinical research; a robust and innovative project management plan; and a cohesive, collaborative approach to working with the Leadership Group (LG), NIAID, other VTEUs and other partners. We have access to state-of-the art clinical and laboratory facilities, including two large inpatient units where human challenge studies are routinely conducted. This proposal describes in further detail our team’s ability to work closely and collaboratively with the LG and NIAID to quickly and cost-efficiently develop concepts, protocols, study designs and proposal plans, and to maintain a flexible infrastructure that can respond with agility to evolving research priorities and public health emergencies requiring large numbers of volunteers. We will incorporate new data as they become available, modify our work to align with these new data and respond rapidly to evolving research priorities. Our broad involvement with advisory committees that address research priorities and public policy enables us to bring the highest priority and most innovative questions to the LG.",,2020,UNIVERSITY OF MARYLAND BALTIMORE,5485854,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P23177,5R01AI148784-05,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,737387,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P23178,5R01GM140564-05,Merging machine learning and mechanistic models to improve prediction and inference in emerging epidemics,"PROJECT SUMMARY When an outbreak of an established or emerging infectious disease occurs we ask a standard set of questions that are critical to a lifesaving public health response: Where will future incidence occur? How many cases will there be? And where can we most effectively intervene? The proposed research is motivated by real world instances where answering these questions was critical to making practical public health decisions, and current methods came up short: from deciding if and where to build additional Ebola Treatment Units in the 2014-15 West African Ebola epidemic, to identifying priority districts where oral cholera vaccine should be used in the 2016-17 cholera outbreak in Yemen, to picking locations where sufficient cases might occur to selecting and prioritizing interventions to slow the spread of COVID-19 worldwide. Forecasts informing such decisions are typically generated either using an epidemic model that relies on knowledge of the disease transmission mechanism and epidemic theory or using a statistical model to project the expected number of cases based on the relationship between covariates and observed counts. However, both approaches are subject to limitations, particularly early in an epidemic when few cases are observed. This project is based on the overarching scientific premise that inferences that combine the strengths of mechanistic epidemic models and statistical covariate models will substantially outperform either approach alone in forecasting and making decisions to confront emerging infectious disease threats. Specifically, this project aims to (1) Develop a framework to forecast incidence in ongoing outbreaks that merges mechanistic and machine learning approaches; (2) Validate the framework using retrospective data and apply the framework to inform decision making in emerging epidemics; (3) Integrate this inferential forecasting framework into causal decision theory to optimize critical actions in the public health response to emerging epidemics; and (4) Develop accessible and extensible tools for forecasting and decision analysis in infectious disease epidemics. We will validate these approaches using rigorous simulation studies and by applying the proposed approaches to retrospective data from important recent epidemics (e.g., Ebola, Cholera and COVID-19, as mentioned above). We will prospectively apply our approach to inform the response to emerging disease threats that occur during the project period, including the ongoing COVID-19 pandemic. To ensure that the tools developed are useful, efficient, and user friendly, we will work with international humanitarian organizations responding to epidemics. Successful completion of these aims will provide a flexible and validated framework for forecasting and decision making during ongoing epidemics, while allowing for innovation in mechanistic and statistical approaches. In doing so it will provide tools to optimize responses and reduce morbidity and mortality during public health crises.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,413057,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Novel Pathogen,,,,,,,,,COVID-19 | Ebola virus disease | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P23181,5R25TW011505-05,United States-Mali Research Ethics Training Program (US-Mali RETP),"Project Summary/Abstract The past four decades, have witnessed a significant increase in public health and clinical research being conducted in Mali, driven partly by increasing international research collaborations and the recent Ebola epidemic. This increase in human research, creates an urgent need for improved bioethics leadership, training, policy and research. It is, therefore, critical and timely to ensure that researchers and members of institutional review board (IRB) in Mali have the requisite knowledge, and capacity to ensure the research meets ethical, cultural, and regulatory expectations. To meet the ethics training needs of Mali, we propose a research ethics capacity building program to strengthen research ethics education and research in Mali through an innovative model of sustainable capacity development to prepare the next generation of ethics researchers. This program will be based on close collaboration between two institutions â€Â"" the George Washington University Milken Institute School of Public Health (GWU), USA and University of Science, Techniques & Technologies of Bamako (USTTB), Mali. The overall goal of the United States-Mali Research Ethics Training Program (US-Mali RETP) is to strengthen research ethics education and research in Mali. Our model will focus on using US and Africa-based expertise to strengthen USTTB’s capacity to develop and lead a new Master’s degree specialization in research ethics and promote a sustainable bioethics enterprise at USTTB through the following specific aims; Specific Aim 1: To enhance the pedagogical and curricular strengths of key USTTB faculty to deliver research ethics courses and mentoring in Mali. We will implement a faculty development program for selected Malian faculty aimed at enhancing analytical capacity in ethics research and training. The selected Malian faculty will participate in intensive courses in US, work with GWSPH faculty in developing curricula and co-delivery of ethics curriculum during year 2. Specific Aim 2: To develop a research ethics specialization within the existing USTTB Masters of Public Health (MPH) program in order to train a core group of professionals with expertise in research ethics in Mali. We will develop a new curriculum in research ethics within the MPH program at USTTB. The Ethics modules will also be offered as part of a one year Diplome. We will also offer short term training workshops and webinars at USTTB including both basic and advanced topics each year. Specific Aim 3: To promote research around key priorities for research ethics in Mali. We will through our trainees conduct relevant national research on ethics to inform public health, training priorities and health care delivery including ethics of research on infectious and emerging diseases as well as genetics and genomics. Specific Aim 4: To create a dedicated “Research Ethics Unit” within USTTB in Mali. We will work to establish an academic Research Unit within USTTB which will coordinate Bioethics research and activities at USTTB and enhance sustainability of our efforts. This unit will also coordinate a national forum to discuss research ethics in Mali in collaboration with the Ministry of Health (MoH) in Mali.",,2024,George Washington University,244580,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in Governance,2020 +P23185,5R01AI148784-04,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,819319,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P23186,5R01AI150888-04,A Fully Integrated Point-of-Care Test for Ebola,"PROJECT SUMMARY The objective of this proposal is to develop a new point-of-care test (POCT)â€Â""the D4 assayâ€Â""for early field- detection of Ebola virus (EBOV) infection. Currently, EBOV is diagnosed by RNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR requires a makeshift BSL-4 grade laboratory in the field, expensive equipment, and highly trained personnel. Other POCTs, including the user-friendly lateral-flow assay (LFA), lack the sensitivity for early detection that is critical for timely intervention with the available antibody cocktail that yields 90% survival rates for patients with low viremia. Our objective is motivated by an urgent clinical need for a POCT that (1) detects EBOV infection in the field quickly and reliably, (2) requires little on-field infrastructure, (3) yields results in 30 min, and (4) matches or exceeds the performance of RT-PCR. To achieve these goals, we have designed an integrated POCT the D4 assay that has four simple stepsâ€Â""dispense, dissolve, diffuse, and detect that require limited handling and skill to perform. This new-frontier technology takes advantage of the presence of an unmistakable, viral secreted glycoprotein sGP that is present in the serum of infected patients very early in infection. We have generated customized monoclonal antibodies (Abs) for sGP to use in the D4 assay. The current prototype D4 assay that we have designed detects EBOV infection at least one day earlier than RT-PCR in infected monkeys and at a far lower cost than RT-PCR or LFA. In this proposal, we plan to advance our development and improve the sensitivity of the D4 assay further as well as reduce the assay time from 60 min to 30 min. Our strategy is to increase the equilibrium binding constant of our current Ab pair from ~10-9 M to ~10-11 M with antibody affinity maturation techniques and high-throughput screening of antibody pairs. The enhanced D4 assay kit will have inkjet-printed capture and detection antibodies on a protein and cell-resistant polymer brush on a glass plate encased in a passive capillarity microfluidics chip. The assay output will be fluorescence of microspots on the D4 chip. We have developed a portable handheld fluorescence detector to capture and image the spots and automatically convert them into the concentration of analytes for quantitation and uploaded to a secure server. The design will be rigorously tested and validated with samples from infected human cells and laboratory-challenged non-human primates. At the completion of this project, we will have a field-ready, user-friendly, and highly sensitive POCT that will allow healthcare workers to detect EBOV in serum, blood, or other bodily fluids in 30 min. The new design will push the current boundaries of EBOV detection and facilitate more expedient deployment of infection control and patient support measures that can yield 90% survival rates or better if implemented early in infection. Because the D4 POCT is multiplexable, it will set a precedent for broader utility beyond EBOV to diagnose many other infectious diseases.",,2025,Duke University,590199,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23187,5DP1AI158125-04,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,1101800,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P23188,3DP1AI158125-04S1,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,228915,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P23189,3DP1AI158125-03S2,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,158112,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P23190,5R01GM140564-04,Merging machine learning and mechanistic models to improve prediction and inference in emerging epidemics,"PROJECT SUMMARY When an outbreak of an established or emerging infectious disease occurs we ask a standard set of questions that are critical to a lifesaving public health response: Where will future incidence occur? How many cases will there be? And where can we most effectively intervene? The proposed research is motivated by real world instances where answering these questions was critical to making practical public health decisions, and current methods came up short: from deciding if and where to build additional Ebola Treatment Units in the 2014-15 West African Ebola epidemic, to identifying priority districts where oral cholera vaccine should be used in the 2016-17 cholera outbreak in Yemen, to picking locations where sufficient cases might occur to selecting and prioritizing interventions to slow the spread of COVID-19 worldwide. Forecasts informing such decisions are typically generated either using an epidemic model that relies on knowledge of the disease transmission mechanism and epidemic theory or using a statistical model to project the expected number of cases based on the relationship between covariates and observed counts. However, both approaches are subject to limitations, particularly early in an epidemic when few cases are observed. This project is based on the overarching scientific premise that inferences that combine the strengths of mechanistic epidemic models and statistical covariate models will substantially outperform either approach alone in forecasting and making decisions to confront emerging infectious disease threats. Specifically, this project aims to (1) Develop a framework to forecast incidence in ongoing outbreaks that merges mechanistic and machine learning approaches; (2) Validate the framework using retrospective data and apply the framework to inform decision making in emerging epidemics; (3) Integrate this inferential forecasting framework into causal decision theory to optimize critical actions in the public health response to emerging epidemics; and (4) Develop accessible and extensible tools for forecasting and decision analysis in infectious disease epidemics. We will validate these approaches using rigorous simulation studies and by applying the proposed approaches to retrospective data from important recent epidemics (e.g., Ebola, Cholera and COVID-19, as mentioned above). We will prospectively apply our approach to inform the response to emerging disease threats that occur during the project period, including the ongoing COVID-19 pandemic. To ensure that the tools developed are useful, efficient, and user friendly, we will work with international humanitarian organizations responding to epidemics. Successful completion of these aims will provide a flexible and validated framework for forecasting and decision making during ongoing epidemics, while allowing for innovation in mechanistic and statistical approaches. In doing so it will provide tools to optimize responses and reduce morbidity and mortality during public health crises.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,458952,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P23192,3F32GM136042-03S1,Asymmetric Nucleophilic Aromatic Substitution Enabled by Hydrogen-Bonding Catalysis,"Project Summary/Abstract Stereogenic-at-phosphorus (P-chiral) P(V) compounds are an increasingly important motif in the design of life- saving pharmaceuticals such as broad spectrum anti-viral medications (Remdesivir, Sofosbuvir, Tenofovir Alafenamide) to treat hepatitis B and C as well as Ebola and COVID-19. Despite the enormous importance of being able to introduce P-chiral centers into compounds to develop new medications to combat existing and emergent diseases, access to this chemical motif remains constrained by a lack of efficient chemical methods. As a result, the diversity of structures that can be efficiently explored and produced in medicinal chemistry research is relatively limited. Existing methods suffer from several limitations: 1) reliance on non-selective synthesis routes, which require additional resolution steps, thus limiting the efficiency of these approaches and 2) the predominant use of electrophilic P(V) substrates that required pre-activation steps to install an appropriately reactive leaving group. Catalytic cross coupling approaches to access P-chiral compounds currently have relatively narrow product scopes and often rely on expensive transition metal catalysts that must be removed assiduously before biological testing. An attractive new approach would be an organocatalytic asymmetric phosphonium dealkylation reaction that generates P-chiral stereogenic centers by coupling P(III) nucleophiles and electrophilic activating agents. This approach would address the previously mentioned key limitations while enabling chemists to catalytically and selectively control the wide range of powerful reactions know to proceed through phosphonium species. Hydrogen-bond donor (HBD) organocatalysts are known to catalyze the formation of ionic species by anion binding while also controlling the stereochemical outcome of nucleophilic trapping of these species. By leveraging the powerful transition state stabilization and synergistic dual nucleophilic and electrophilic activation capabilities unique to HBD catalysts, this approach should enable phosphonium desymmetrization to be accomplished with exquisite enantioselectivity. The goal of this proposal is to design an anion pair binding organocatalyst to promote the first catalytic enantioselective phosphonium dealkylation reaction capable of producing P-chiral products. The research plan outlines a strategy to develop such a catalyst system guided by hypothesis-driven experimentation, computational modeling, and structure-activity studies. To add to the information gained in the reaction development, a detailed mechanistic study of HBD organocatalyst activation of simple phosphorus (III) substrates such as phosphonites and phosphites will be undertaken using data-intensive multi-dimensional correlation. This study will enable simple reagents to be utilized to produce medicinally relevant enantioenriched compounds in a novel manner, contributing enormously to medicinal research, catalyst development, and substantially contributing to scientific knowledge.",,2023,Harvard University,35896,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23194,5R25TW011505-04,United States-Mali Research Ethics Training Program (US-Mali RETP),"Project Summary/Abstract The past four decades, have witnessed a significant increase in public health and clinical research being conducted in Mali, driven partly by increasing international research collaborations and the recent Ebola epidemic. This increase in human research, creates an urgent need for improved bioethics leadership, training, policy and research. It is, therefore, critical and timely to ensure that researchers and members of institutional review board (IRB) in Mali have the requisite knowledge, and capacity to ensure the research meets ethical, cultural, and regulatory expectations. To meet the ethics training needs of Mali, we propose a research ethics capacity building program to strengthen research ethics education and research in Mali through an innovative model of sustainable capacity development to prepare the next generation of ethics researchers. This program will be based on close collaboration between two institutions â€Â"" the George Washington University Milken Institute School of Public Health (GWU), USA and University of Science, Techniques & Technologies of Bamako (USTTB), Mali. The overall goal of the United States-Mali Research Ethics Training Program (US-Mali RETP) is to strengthen research ethics education and research in Mali. Our model will focus on using US and Africa-based expertise to strengthen USTTB’s capacity to develop and lead a new Master’s degree specialization in research ethics and promote a sustainable bioethics enterprise at USTTB through the following specific aims; Specific Aim 1: To enhance the pedagogical and curricular strengths of key USTTB faculty to deliver research ethics courses and mentoring in Mali. We will implement a faculty development program for selected Malian faculty aimed at enhancing analytical capacity in ethics research and training. The selected Malian faculty will participate in intensive courses in US, work with GWSPH faculty in developing curricula and co-delivery of ethics curriculum during year 2. Specific Aim 2: To develop a research ethics specialization within the existing USTTB Masters of Public Health (MPH) program in order to train a core group of professionals with expertise in research ethics in Mali. We will develop a new curriculum in research ethics within the MPH program at USTTB. The Ethics modules will also be offered as part of a one year Diplome. We will also offer short term training workshops and webinars at USTTB including both basic and advanced topics each year. Specific Aim 3: To promote research around key priorities for research ethics in Mali. We will through our trainees conduct relevant national research on ethics to inform public health, training priorities and health care delivery including ethics of research on infectious and emerging diseases as well as genetics and genomics. Specific Aim 4: To create a dedicated “Research Ethics Unit” within USTTB in Mali. We will work to establish an academic Research Unit within USTTB which will coordinate Bioethics research and activities at USTTB and enhance sustainability of our efforts. This unit will also coordinate a national forum to discuss research ethics in Mali in collaboration with the Ministry of Health (MoH) in Mali.",,2024,George Washington University,241777,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,,2020 +P23196,5DP1AI158124-04,A functional evolutionary genetic approach to combat viral infection,"Project Summary Humans are under increasing threat from viruses that spill over from animal reservoirs. Most of these viral diseases lack targeted treatments. We speculate that this unmet medical need might be addressable by first understanding the evolutionary principles underlying antiviral immune responses. A major component of innate immunity in mammals is the interferon response. Interferon induces hundreds of genes, many of which encode effector proteins that suppress viral infection. In mammals, these antiviral effectors are rapidly evolving, most likely in response to the genetic ""arms race"" continually occurring between virus and host. Further, certain mammalian orders, such as primates, rodents, bats, and carnivores, are particularly rich in viruses that have the potential to spill over into humans. We hypothesize that the genomes of these viral zoonotic reservoirs encode unique antiviral effectors that may be harnessed to combat human viral pathogens. The goals of this project are to identify, characterize, and validate the efficacy of novel antiviral proteins from diverse non-model mammalian species. State-of-the-art genetic screening platforms will be used to discover antiviral genes in primary cell cultures obtained from multiples species in the following mammalian orders: Primate, Rodentia, Chiroptera, and Carnivora. Validated effectors will be characterized mechanistically with a suite of virological, biochemical, molecular, and cell biological approaches. The potential for these effectors to suppress human viruses will be tested in murine models of human viral disease. Outcomes will include the creation of the first comprehensive Mammalian Antiviral Protein Atlas, the discovery of new genetically-encoded antiviral mechanisms, and proof-of- concept that human viral disease can be thwarted by naturally occurring proteins from other species. The impact of this proposal will be the development of a new area of biomedical research at the intersection of virology, immunology, and evolutionary biology. Long term prospects include harnessing the results of these studies to inspire alternative approaches to antiviral drug development.",,2025,UT SOUTHWESTERN MEDICAL CENTER,1148000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P23207,5F31AI172187-02,Statistical Methods for Improving Real-Time Public Health Surveillance and Integrated Outbreak Detection,"Project Summary/Abstract The COVID-19 pandemic has accentuated the need for strong monitoring and surveillance systems. To conduct early detection and response to emerging infectious diseases, there must be robust analytical tools that examine historical and current data in order to identify potential aberrations in key health indicators. This is especially needed when reliable testing and reporting data is lacking. Instead, key associated indicators, namely mortality and related symptoms to a disease of interest, can be tracked and analyzed. Two problems exist: (1) reporting delays lead to undercounts in current health indicators data, and (2) prior anomalies such as spikes in mortality due to past outbreaks distort historical or baseline data. Thus, the goal is to develop methods to conduct ongoing, rolling surveillance and outbreak detection in the context of these two issues. Two large datasets resulting from collaborations are available: (1) state-level mortality data from the Centers for Disease Control and Prevention (CDC) and Departments of Public Health (DPH) in Puerto Rico, Massachusetts, and California from January 2017-December 2021, and (2) Partners in Health (PIH) routinely collected health management information systems (HMIS) data on COVID-19-associated indicators, specifically acute respiratory infections (ARI) from 900 health facilities in 8 countries from January 2016-current. Through the first aim of the proposed research plan, the first dataset will be analyzed to develop methods for imputing undercounts in current data. In doing so, various methodological gaps in existing research will be addressed, including accounting for seasonality in reporting lag patterns and providing measures of uncertainty around estimates. Through the second aim of the proposed research plan, the second dataset set, along with a simulated version, will be analyzed to develop methods for rolling outbreak detection by simultaneously addressing two gaps: accounting for prior data aberrations and optimizing key statistical properties including bias, variance, and appropriate model fit. Both goals are complementary and equally important in infectious disease surveillance. While the specific datasets and indicators as described above will be analyzed, the developed methods will be broadly applicable to monitoring of any key health indicators. As COVID-19-related challenges persist and new threats emerge, statistically rigorous tools for early detection remain of paramount importance. Just as important is dissemination of these tools in accessible, easily usable open-source software packages, a key aspect of the proposed research plan.",,2024,HARVARD SCHOOL OF PUBLIC HEALTH,33716,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2022 +P23212,5R01AI151176-04,"Accelerating viral outbreak detection in US cities using mechanistic models, machine learning and diverse geospatial data","Project Abstract/Summary Our interdisciplinary research team will develop algorithms to accelerate the detection of respiratory virus outbreaks at an unprecedented local scale in US cities. We propose to advance outbreak detection by combining machine learning data integration methods and spatial models of disease transmission. The dynamic models that will be developed will provide mechanistic engines for distinguishing typical from atypical disease trends and the optimization methods evaluate the informativeness of data sources to achieve specified public health goals through the rapid evaluation of diverse input data sources. Working with local healthcare and public health leaders, we will translate the algorithms into user-friendly online tools to support preparedness plans and decision-making. Our proposed research is organized around three major aims. In Aim 1, we will apply machine learning and signal processing methods to build systems that track the earliest indicators of emerging outbreaks within seven US cities. We will evaluate non-clinical data reflecting early and mild symptoms as well as clinical data covering underserved communities and geographic and demographic hotspots for viral emergence. In Aim 2, we will develop sub-city scale models reflecting the syndemics of co-circulating respiratory viruses and chronic respiratory diseases (CRD) that can exacerbate viral infections. We will infer viral transmission rates and socio-environmental risk cofactors by fitting the model to respiratory disease data extracted from millions of electronic health records (EHRs) for the last nine years. We will then partner with clinical and EHR experts to translate our models into the first outbreak detection system for severe respiratory viruses that incorporates EHR data on CRDs. Using machine learning techniques, we will further integrate other surveillance, environmental, behavioral and internet predictor data sources to maximize the accuracy, sensitivity, speed and population coverage of our algorithms. In Aim 3, we will develop an open-access Python toolkit to facilitate the integration of next generation data into outbreak surveillance models. This project will produce practical early warning algorithms for detecting emerging viral threats at high spatiotemporal resolution in several US cities, elucidate socio-geographic gaps in current surveillance systems and hotspots for viral emergence, and provide a robust design framework for extrapolating these algorithms to other US cities.",,2025,Yale University,574999,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P23213,75N91019D00024-0-759102200015-1,"NIAID-VRC-Research, Development, and Production to Support Ebola Bispecific Antibody Development","The NIAID mission and scope includes rapidly responding to infectious disease outbreaks and preparing for future pandemics through clinical product development, reagent production, and manufacturing. In following this mission, the VRC has prioritized development of vaccines and antibodies targeting Ebola that may lead to prevention and/or therapeutic treatment. Specifically, the VRC seeks to develop and manufacture Ebola bispecific antibody products.",,2027,"LEIDOS BIOMEDICAL RESEARCH, INC.",2765029,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments | Therapeutics logistics and supply chains and distribution strategies,2022 +P23214,5R01AI148784-03,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,819319,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P23215,5R01AI150888-03,A Fully Integrated Point-of-Care Test for Ebola,"PROJECT SUMMARY The objective of this proposal is to develop a new point-of-care test (POCT)â€Â""the D4 assayâ€Â""for early field- detection of Ebola virus (EBOV) infection. Currently, EBOV is diagnosed by RNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR requires a makeshift BSL-4 grade laboratory in the field, expensive equipment, and highly trained personnel. Other POCTs, including the user-friendly lateral-flow assay (LFA), lack the sensitivity for early detection that is critical for timely intervention with the available antibody cocktail that yields 90% survival rates for patients with low viremia. Our objective is motivated by an urgent clinical need for a POCT that (1) detects EBOV infection in the field quickly and reliably, (2) requires little on-field infrastructure, (3) yields results in 30 min, and (4) matches or exceeds the performance of RT-PCR. To achieve these goals, we have designed an integrated POCT the D4 assay that has four simple stepsâ€Â""dispense, dissolve, diffuse, and detect that require limited handling and skill to perform. This new-frontier technology takes advantage of the presence of an unmistakable, viral secreted glycoprotein sGP that is present in the serum of infected patients very early in infection. We have generated customized monoclonal antibodies (Abs) for sGP to use in the D4 assay. The current prototype D4 assay that we have designed detects EBOV infection at least one day earlier than RT-PCR in infected monkeys and at a far lower cost than RT-PCR or LFA. In this proposal, we plan to advance our development and improve the sensitivity of the D4 assay further as well as reduce the assay time from 60 min to 30 min. Our strategy is to increase the equilibrium binding constant of our current Ab pair from ~10-9 M to ~10-11 M with antibody affinity maturation techniques and high-throughput screening of antibody pairs. The enhanced D4 assay kit will have inkjet-printed capture and detection antibodies on a protein and cell-resistant polymer brush on a glass plate encased in a passive capillarity microfluidics chip. The assay output will be fluorescence of microspots on the D4 chip. We have developed a portable handheld fluorescence detector to capture and image the spots and automatically convert them into the concentration of analytes for quantitation and uploaded to a secure server. The design will be rigorously tested and validated with samples from infected human cells and laboratory-challenged non-human primates. At the completion of this project, we will have a field-ready, user-friendly, and highly sensitive POCT that will allow healthcare workers to detect EBOV in serum, blood, or other bodily fluids in 30 min. The new design will push the current boundaries of EBOV detection and facilitate more expedient deployment of infection control and patient support measures that can yield 90% survival rates or better if implemented early in infection. Because the D4 POCT is multiplexable, it will set a precedent for broader utility beyond EBOV to diagnose many other infectious diseases.",,2025,Duke University,772176,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23216,5DP1AI158125-03,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,807602,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P23218,5R01GM140564-03,Merging machine learning and mechanistic models to improve prediction and inference in emerging epidemics,"PROJECT SUMMARY When an outbreak of an established or emerging infectious disease occurs we ask a standard set of questions that are critical to a lifesaving public health response: Where will future incidence occur? How many cases will there be? And where can we most effectively intervene? The proposed research is motivated by real world instances where answering these questions was critical to making practical public health decisions, and current methods came up short: from deciding if and where to build additional Ebola Treatment Units in the 2014-15 West African Ebola epidemic, to identifying priority districts where oral cholera vaccine should be used in the 2016-17 cholera outbreak in Yemen, to picking locations where sufficient cases might occur to selecting and prioritizing interventions to slow the spread of COVID-19 worldwide. Forecasts informing such decisions are typically generated either using an epidemic model that relies on knowledge of the disease transmission mechanism and epidemic theory or using a statistical model to project the expected number of cases based on the relationship between covariates and observed counts. However, both approaches are subject to limitations, particularly early in an epidemic when few cases are observed. This project is based on the overarching scientific premise that inferences that combine the strengths of mechanistic epidemic models and statistical covariate models will substantially outperform either approach alone in forecasting and making decisions to confront emerging infectious disease threats. Specifically, this project aims to (1) Develop a framework to forecast incidence in ongoing outbreaks that merges mechanistic and machine learning approaches; (2) Validate the framework using retrospective data and apply the framework to inform decision making in emerging epidemics; (3) Integrate this inferential forecasting framework into causal decision theory to optimize critical actions in the public health response to emerging epidemics; and (4) Develop accessible and extensible tools for forecasting and decision analysis in infectious disease epidemics. We will validate these approaches using rigorous simulation studies and by applying the proposed approaches to retrospective data from important recent epidemics (e.g., Ebola, Cholera and COVID-19, as mentioned above). We will prospectively apply our approach to inform the response to emerging disease threats that occur during the project period, including the ongoing COVID-19 pandemic. To ensure that the tools developed are useful, efficient, and user friendly, we will work with international humanitarian organizations responding to epidemics. Successful completion of these aims will provide a flexible and validated framework for forecasting and decision making during ongoing epidemics, while allowing for innovation in mechanistic and statistical approaches. In doing so it will provide tools to optimize responses and reduce morbidity and mortality during public health crises.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,458952,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Novel Pathogen,,,,,,,,,COVID-19 | Ebola virus disease | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P23219,1G20AI174728-01,A Bedside-to-Bench Approach to Pandemic Preparedness,"The clinical capabilities of the University of Nebraska Medical Center (UNMC) and its clinical partner, Nebraska Medicine (NM), played vital roles in the treatment of U.S. citizens infected with Ebola in 2014 and the early response to the COVID-19 pandemic. While the presence of the National Quarantine Unit (NQU) and the Nebraska Biocontainment Unit (NBU) on campus provided UNMC researchers with some of the earliest access to individuals exposed to infectious agents (in the NQU), as well as those who begin to develop disease (in the NBU), we recognized a key gap in our capabilities is the lack of modern technologies within our high- containment spaces required to gain greater insights into the pathogenic mechanisms utilized by new and emerging pathogens. Therefore, the overall goal of this proposed project is to modernize our high-containment research laboratories to maximize their research potential and to leverage our clinical expertise to foster research on vaccine and therapeutic development. This will be achieved in two ways: First, we will improve our biocontainment infrastructure within key biocontainment research facilities in a way that increases our capacity to conduct research on high-consequence pathogens, maximizes synergy between the various biocontainment laboratories, and increases biosecurity. Second, we will invest in the modern technologies needed in our BSL-3 and ABSL-3 laboratories to conduct cutting-edge studies on new and emerging pathogens and to address critical questions related to disease pathogenesis. Upon completion, these improvements will foster much greater synergy between the clinical and research arms of UNMC and NM, leveraging early access to clinical data/samples to streamline research into disease pathogenesis, and to accelerate the development of new vaccines and therapeutics during future pandemics.",,2025,University Of Nebraska Medical Center,3906967,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2022 +P23221,5R25TW011505-03,United States-Mali Research Ethics Training Program (US-Mali RETP),"Project Summary/Abstract The past four decades, have witnessed a significant increase in public health and clinical research being conducted in Mali, driven partly by increasing international research collaborations and the recent Ebola epidemic. This increase in human research, creates an urgent need for improved bioethics leadership, training, policy and research. It is, therefore, critical and timely to ensure that researchers and members of institutional review board (IRB) in Mali have the requisite knowledge, and capacity to ensure the research meets ethical, cultural, and regulatory expectations. To meet the ethics training needs of Mali, we propose a research ethics capacity building program to strengthen research ethics education and research in Mali through an innovative model of sustainable capacity development to prepare the next generation of ethics researchers. This program will be based on close collaboration between two institutions â€Â"" the George Washington University Milken Institute School of Public Health (GWU), USA and University of Science, Techniques & Technologies of Bamako (USTTB), Mali. The overall goal of the United States-Mali Research Ethics Training Program (US-Mali RETP) is to strengthen research ethics education and research in Mali. Our model will focus on using US and Africa-based expertise to strengthen USTTB’s capacity to develop and lead a new Master’s degree specialization in research ethics and promote a sustainable bioethics enterprise at USTTB through the following specific aims; Specific Aim 1: To enhance the pedagogical and curricular strengths of key USTTB faculty to deliver research ethics courses and mentoring in Mali. We will implement a faculty development program for selected Malian faculty aimed at enhancing analytical capacity in ethics research and training. The selected Malian faculty will participate in intensive courses in US, work with GWSPH faculty in developing curricula and co-delivery of ethics curriculum during year 2. Specific Aim 2: To develop a research ethics specialization within the existing USTTB Masters of Public Health (MPH) program in order to train a core group of professionals with expertise in research ethics in Mali. We will develop a new curriculum in research ethics within the MPH program at USTTB. The Ethics modules will also be offered as part of a one year Diplome. We will also offer short term training workshops and webinars at USTTB including both basic and advanced topics each year. Specific Aim 3: To promote research around key priorities for research ethics in Mali. We will through our trainees conduct relevant national research on ethics to inform public health, training priorities and health care delivery including ethics of research on infectious and emerging diseases as well as genetics and genomics. Specific Aim 4: To create a dedicated “Research Ethics Unit” within USTTB in Mali. We will work to establish an academic Research Unit within USTTB which will coordinate Bioethics research and activities at USTTB and enhance sustainability of our efforts. This unit will also coordinate a national forum to discuss research ethics in Mali in collaboration with the Ministry of Health (MoH) in Mali.",,2024,George Washington University,242669,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,,2020 +P23223,7K08EB033409-02,Development of Optofluidic Resonators for Filoviral Detection,"Project Summary/Abstract This proposal describes a 4-year career development plan for the PI, Dr. Abraham J. Qavi, MD, PhD, with the goal of preparing him for an independent research career as a physician scientist. This plan includes expand training opportunities and a pathway to an independent career that includes the development and implementation of sensor technologies and its application towards filoviruses, namely Ebola. The PI graduated with degrees in Biochemistry & Molecular Biology and Chemistry from the University of California, Irvine. He then enrolled in the Medical Scholars Program at the University of Illinois at Urbana-Champaign, where he earned his MD and PhD in Chemistry. Dr. Qavi continued his medical training as part of the Clinical Pathology Physician Scientist Training Program at Washington University in St. Louis and the Barnes-Jewish Hospital consortium. During his residency elective time, he began research in the laboratory of Dr. Lan Yang, who will serve as his co-mentor together with Dr. Amarasinghe. Dr. Yang is the Edwin H. and Florence G. Skinner Professor of Electrical & Systems Engineering, and an internationally renowned researcher in photonics. In 2019, Dr. Qavi added an additional training component under the co-mentorship with Dr. Gaya Amarasinghe, Professor of Pathology & Immunology, to expand the application of his previously developed sensor technology to infectious disease reach. The goal of this study is the development of a rapid, multiplexed optofluidic sensor platform for the rapid detection of pathogens, with an initial focus on Ebola. Filoviruses, such as Ebola, are among the most lethal human pathogens, with high case fatality rates during outbreaks. Critical in the identification and management of outbreaks are robust detection methods that can be implemented rapidly and sensitively. To address this critical need, Whispering Gallery Mode (WGM) sensors will be leveraged. WGM devices are a class of optical sensors in which light is confined within a micron-scale volume. These devices have incredibly high sensitivity, small sensor footprint, ease of integration with conventional electronics, and low fabrication costs. Microbubble resonators (MBRs), a subclass of WGM sensors, offer the advantages of conventional WGM devices while enabling coupling of optical and the fluidic components into a single component. The goal of this proposal is the use of an optofluidic sensor platform based on MBRs for the rapid, multiplexed detection of Ebola. The workflow and advancements, including MBR development, engineered antibodies, biophysical validation and multiplexing, will provide the framework to extend the work beyond the initial goals and promote facile transition to an independent career for Dr. Qavi.",,2026,University Of California-Irvine,116640,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23225,1R43CK000680-01,"SBIR, Phase I (R43): Ultrasensitive Lateral Flow Assays Enabled by Fluorescent Nanodiamond Labels","Summary. Lateral flow assays (LFAs) providing rapid on-site detection of medically significant analytes could be extremely valuable for high-volume, high-speed population screening necessary to minimize the economic and societal impact of epidemic outbreaks. However, LFA performance has been mostly limited to colorimetric binary diagnostics, primarily providing yes/no testing for clinically relevant analytes present at high concentrations (Ã'µM-nM) and cannot satisfy sensitivity requirements for reliable virus detection (fM-aM) which is presently achieved only using laboratory techniques (ELISA, PCR). Though signal amplification through fluorescence has steadily gained traction to improve sensitivity by 1-2 orders of magnitude in comparison with standard colorimetric tests, the inherent autofluorescence of materials used to construct LFA test strips interferes with test performance and introduces variability. By enabling rapid, attomolar sensitivity, fluorescence-based LFAs could facilitate a revolutionary shift in the analytical capability of point-of-care tests to provide quantitative actionable data to inform health authorities to launch timely responses. The pathway to this development involves advancement of the fluorescence detection system and material properties of the reporters. This proposal aims to strategically address both of these directions by advancing a recently emerged LFA platform based on fluorescent nanodiamond (FND) reporters. FNDs possess ideal features for an LFA reporter such as bright non- bleaching fluorescence and unsurpassed ruggedness. A prototype using FND as a novel LFA reporter was recently demonstrated by Debina Diagnostics in detecting Ebola virus glycoprotein at the picograms level, using a custom-made optoelectronic reader (Axxin, Inc.) and off-the-shelf 200 nm FND produced by Adámas Nanotechnologies. The most striking attribute of FND envisioned to improve FND-based LFA sensitivity by 2-3 orders of magnitude arises from the uniquely coupled magneto-optical properties of the particles, where nitrogen- vacancy (NV) color centers with an electron spin allow the intensity FND fluorescence to be modulated by an external magnetic field. Based on this unique property, the FND-related signal can be separated from background autofluorescence in the frequency domain through lock-in analysis which is widely used in signal processing to extract small periodic signals present below noise levels. Lock-in signal processing of FND can allow up to 100x increase in sensitivity, as was demonstrated in bioimaging including recent results in LFA. Adámas recently developed a method further increasing magnetic modulation contrast by 3-5 folds. In this proposal, Adámas and Debina join their efforts to tailor FND material properties in order to eliminate non-specific retention of particles on the LFA strip by modifying their physical (shape, size) and chemical (coating) properties, while optimizing brightness and magneto-optical properties (aim 1). After implementation and optimization of the lock-in analysis including interfacing the set-up with the opto-electronic reader (aim 2), we aim to demonstrate >300x improvement in LOD of Ebola virus antigen and <1pg LOD for detection of SARS-CoV-2 antigen (aim 3).",,2023,"ADAMAS NANOTECHNOLOGIES, INC.",285269,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23226,5DP1AI158124-03,A functional evolutionary genetic approach to combat viral infection,"Project Summary Humans are under increasing threat from viruses that spill over from animal reservoirs. Most of these viral diseases lack targeted treatments. We speculate that this unmet medical need might be addressable by first understanding the evolutionary principles underlying antiviral immune responses. A major component of innate immunity in mammals is the interferon response. Interferon induces hundreds of genes, many of which encode effector proteins that suppress viral infection. In mammals, these antiviral effectors are rapidly evolving, most likely in response to the genetic ""arms race"" continually occurring between virus and host. Further, certain mammalian orders, such as primates, rodents, bats, and carnivores, are particularly rich in viruses that have the potential to spill over into humans. We hypothesize that the genomes of these viral zoonotic reservoirs encode unique antiviral effectors that may be harnessed to combat human viral pathogens. The goals of this project are to identify, characterize, and validate the efficacy of novel antiviral proteins from diverse non-model mammalian species. State-of-the-art genetic screening platforms will be used to discover antiviral genes in primary cell cultures obtained from multiples species in the following mammalian orders: Primate, Rodentia, Chiroptera, and Carnivora. Validated effectors will be characterized mechanistically with a suite of virological, biochemical, molecular, and cell biological approaches. The potential for these effectors to suppress human viruses will be tested in murine models of human viral disease. Outcomes will include the creation of the first comprehensive Mammalian Antiviral Protein Atlas, the discovery of new genetically-encoded antiviral mechanisms, and proof-of- concept that human viral disease can be thwarted by naturally occurring proteins from other species. The impact of this proposal will be the development of a new area of biomedical research at the intersection of virology, immunology, and evolutionary biology. Long term prospects include harnessing the results of these studies to inspire alternative approaches to antiviral drug development.",,2025,UT SOUTHWESTERN MEDICAL CENTER,1148000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P23229,1R43GM145194-01,System for unitary automation of library preparation,"ABSTRACT Genomic epidemiology is crucial to outbreak surveillance and response. Sequencing data lets us track virus evolution in real time and thus characterize transmission chains, identify emerging variants, and predict future spread. This information, which cannot be deduced from diagnostic testing alone, informs the severity and speed of an outbreak before it becomes a pandemic. In order to inform corrective action from sequencing data, results must be obtained within hours, instead of days. Ideally, automated library preparation would be achieved with an easy-to-use, single button device that can be deployed in resource-limited settings as part of a point-of-need infectious disease surveillance/diagnostic system. However, given the diversity of sequencing applications, there cannot be a one-size-fits-all solution to library prep. Instead, we believe the correct strategy is to automate unitary library prep operations, with well-defined breakpoints in between, enabling the user to mix and match these operations as the application demands. This strategy will reduce hands-on time and operator burden while maintaining workflow flexibility. In this Phase I project, we focus on demonstrating the feasibility of automating three unitary library prep operations on our platform. The operations are: end repair/dA-tailing, barcoding, and adapter ligation. Each step involves an incubation followed by size selection. Our approach protects the customizability of manual workflows while eliminating up to 95% of pipette steps. The outcome of this project will be a solution for pre-analytical preparation in low-resource settings.",,2023,"REDBUD LABS, INC.",292788,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,Health Systems Research,"Medicines, vaccines & other technologies | Health information systems",2022 +P23235,1F31AI172187-01,Statistical Methods for Improving Real-Time Public Health Surveillance and Integrated Outbreak Detection,"Project Summary/Abstract The COVID-19 pandemic has accentuated the need for strong monitoring and surveillance systems. To conduct early detection and response to emerging infectious diseases, there must be robust analytical tools that examine historical and current data in order to identify potential aberrations in key health indicators. This is especially needed when reliable testing and reporting data is lacking. Instead, key associated indicators, namely mortality and related symptoms to a disease of interest, can be tracked and analyzed. Two problems exist: (1) reporting delays lead to undercounts in current health indicators data, and (2) prior anomalies such as spikes in mortality due to past outbreaks distort historical or baseline data. Thus, the goal is to develop methods to conduct ongoing, rolling surveillance and outbreak detection in the context of these two issues. Two large datasets resulting from collaborations are available: (1) state-level mortality data from the Centers for Disease Control and Prevention (CDC) and Departments of Public Health (DPH) in Puerto Rico, Massachusetts, and California from January 2017-December 2021, and (2) Partners in Health (PIH) routinely collected health management information systems (HMIS) data on COVID-19-associated indicators, specifically acute respiratory infections (ARI) from 900 health facilities in 8 countries from January 2016-current. Through the first aim of the proposed research plan, the first dataset will be analyzed to develop methods for imputing undercounts in current data. In doing so, various methodological gaps in existing research will be addressed, including accounting for seasonality in reporting lag patterns and providing measures of uncertainty around estimates. Through the second aim of the proposed research plan, the second dataset set, along with a simulated version, will be analyzed to develop methods for rolling outbreak detection by simultaneously addressing two gaps: accounting for prior data aberrations and optimizing key statistical properties including bias, variance, and appropriate model fit. Both goals are complementary and equally important in infectious disease surveillance. While the specific datasets and indicators as described above will be analyzed, the developed methods will be broadly applicable to monitoring of any key health indicators. As COVID-19-related challenges persist and new threats emerge, statistically rigorous tools for early detection remain of paramount importance. Just as important is dissemination of these tools in accessible, easily usable open-source software packages, a key aspect of the proposed research plan.",,2024,HARVARD SCHOOL OF PUBLIC HEALTH,38696,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2022 +P23240,3UM1AI148689-03S7,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,1188978,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2020 +P23241,3UM1AI148689-03S3,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,2098592,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23242,3UM1AI148689-03S4,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,1818913,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2022 +P23243,3UM1AI148689-03S2,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,563973,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23244,3UM1AI148689-03S5,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,1813428,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23245,3UM1AI148689-03S6,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,169734,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23246,3UM1AI148689-03S1,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2023,University Of Maryland Baltimore,298077,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23247,5R01AI151176-03,"Accelerating viral outbreak detection in US cities using mechanistic models, machine learning and diverse geospatial data","Project Abstract/Summary Our interdisciplinary research team will develop algorithms to accelerate the detection of respiratory virus outbreaks at an unprecedented local scale in US cities. We propose to advance outbreak detection by combining machine learning data integration methods and spatial models of disease transmission. The dynamic models that will be developed will provide mechanistic engines for distinguishing typical from atypical disease trends and the optimization methods evaluate the informativeness of data sources to achieve specified public health goals through the rapid evaluation of diverse input data sources. Working with local healthcare and public health leaders, we will translate the algorithms into user-friendly online tools to support preparedness plans and decision-making. Our proposed research is organized around three major aims. In Aim 1, we will apply machine learning and signal processing methods to build systems that track the earliest indicators of emerging outbreaks within seven US cities. We will evaluate non-clinical data reflecting early and mild symptoms as well as clinical data covering underserved communities and geographic and demographic hotspots for viral emergence. In Aim 2, we will develop sub-city scale models reflecting the syndemics of co-circulating respiratory viruses and chronic respiratory diseases (CRD) that can exacerbate viral infections. We will infer viral transmission rates and socio-environmental risk cofactors by fitting the model to respiratory disease data extracted from millions of electronic health records (EHRs) for the last nine years. We will then partner with clinical and EHR experts to translate our models into the first outbreak detection system for severe respiratory viruses that incorporates EHR data on CRDs. Using machine learning techniques, we will further integrate other surveillance, environmental, behavioral and internet predictor data sources to maximize the accuracy, sensitivity, speed and population coverage of our algorithms. In Aim 3, we will develop an open-access Python toolkit to facilitate the integration of next generation data into outbreak surveillance models. This project will produce practical early warning algorithms for detecting emerging viral threats at high spatiotemporal resolution in several US cities, elucidate socio-geographic gaps in current surveillance systems and hotspots for viral emergence, and provide a robust design framework for extrapolating these algorithms to other US cities.",,2025,Yale University,574999,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P23251,3R01AI148784-02S1,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2021,UNIV OF MASSACHUSETTS MED SCH WORCESTER,27920,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P23252,5R01AI148784-02,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,791399,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P23253,5R01AI150888-02,A Fully Integrated Point-of-Care Test for Ebola,"PROJECT SUMMARY The objective of this proposal is to develop a new point-of-care test (POCT)â€Â""the D4 assayâ€Â""for early field- detection of Ebola virus (EBOV) infection. Currently, EBOV is diagnosed by RNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR requires a makeshift BSL-4 grade laboratory in the field, expensive equipment, and highly trained personnel. Other POCTs, including the user-friendly lateral-flow assay (LFA), lack the sensitivity for early detection that is critical for timely intervention with the available antibody cocktail that yields 90% survival rates for patients with low viremia. Our objective is motivated by an urgent clinical need for a POCT that (1) detects EBOV infection in the field quickly and reliably, (2) requires little on-field infrastructure, (3) yields results in 30 min, and (4) matches or exceeds the performance of RT-PCR. To achieve these goals, we have designed an integrated POCT the D4 assay that has four simple stepsâ€Â""dispense, dissolve, diffuse, and detect that require limited handling and skill to perform. This new-frontier technology takes advantage of the presence of an unmistakable, viral secreted glycoprotein sGP that is present in the serum of infected patients very early in infection. We have generated customized monoclonal antibodies (Abs) for sGP to use in the D4 assay. The current prototype D4 assay that we have designed detects EBOV infection at least one day earlier than RT-PCR in infected monkeys and at a far lower cost than RT-PCR or LFA. In this proposal, we plan to advance our development and improve the sensitivity of the D4 assay further as well as reduce the assay time from 60 min to 30 min. Our strategy is to increase the equilibrium binding constant of our current Ab pair from ~10-9 M to ~10-11 M with antibody affinity maturation techniques and high-throughput screening of antibody pairs. The enhanced D4 assay kit will have inkjet-printed capture and detection antibodies on a protein and cell-resistant polymer brush on a glass plate encased in a passive capillarity microfluidics chip. The assay output will be fluorescence of microspots on the D4 chip. We have developed a portable handheld fluorescence detector to capture and image the spots and automatically convert them into the concentration of analytes for quantitation and uploaded to a secure server. The design will be rigorously tested and validated with samples from infected human cells and laboratory-challenged non-human primates. At the completion of this project, we will have a field-ready, user-friendly, and highly sensitive POCT that will allow healthcare workers to detect EBOV in serum, blood, or other bodily fluids in 30 min. The new design will push the current boundaries of EBOV detection and facilitate more expedient deployment of infection control and patient support measures that can yield 90% survival rates or better if implemented early in infection. Because the D4 POCT is multiplexable, it will set a precedent for broader utility beyond EBOV to diagnose many other infectious diseases.",,2025,Duke University,717426,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23254,272201700050I-0-759302100008-1,FINANCIAL MANAGEMENT SERVICES IN SUPPORT OF DCR SPECIAL PROJECTS (GUINEA SERVICE CENTER) FOR CONTRACT #HHSN2201700050I.,"This funding supports core clinical research infrastructure to facilitate multicenter, randomized, controlled clinical trials on Ebola virus, HIV, Malaria, and other infectious diseases in Guinea.",,2022,MITCHELL GROUP INC,564034,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2021 +P23255,5DP1AI158125-02,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,1101975,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P23256,1DP2GM146321-01,Elucidating the mechanisms of viral life cycles under near-native conditions,"Project Summary Mononegavirales is a taxonomic order of viruses, so classified for their negative sense single stranded RNA genome and their pleomorphic membrane-enveloped virions. Mononegavirus life cycles involve a number of different events, including entry of virions into host cells, viral mRNA transcription, genome replication and virus assembly, and viral budding from host cells. These events are carried out through molecular interactions between virus and host cell machinery; elucidating these interactions is key to understanding viral life cycles and identifying potential therapeutic targets. Studies of viral machinery are typically limited to isolated particles or assemblies; this removes them from their native environments and strips away important molecular interactions. To preserve biological context, viral machinery must be studied in situ, i.e. under near-native conditions, such as within intact virions or cells. These environments are a complex, disordered mixture of molecules, making it particularly difficult to obtain molecular resolution information. Here, we propose to study three mononegaviruses: measles, rabies, and Ebola viruses. Each serve as prototypical viruses for their taxonomic families, and each are pathogens important to global health. To carry out our proposed research, we will use and develop in situ structural biology methods. Our primary method will be cryo-electron tomography (cryo-ET), a type of cryo-electron microscopy (cryo-EM) that allows for visualization of three-dimensional volumes. This overcomes the typical cryo-EM requirement of thin monolayers of purified particles, allowing for the acquisition of molecular-resolution information in near-native environments. We will develop data collection and computational methods for cryo-ET to enable rapid, automated data collection, high-resolution structure determination, and accurate molecular identification. We will also use and develop methods complementary to cryo-ET including focused ion-beam milling and correlative light and electron microscopy approaches. Our research will provide novel biological insights three important viruses, but more broadly, it will demonstrate a transformative approach for studying viruses. Rather than trying to tease apart function and interactions through indirect biochemical means, our research will provide an infrastructure to directly observe the virus and host cell machinery with complete biological contexts under near-native conditions.",,2024,Vanderbilt University,1426500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P23257,1R01GM140564-01,Merging machine learning and mechanistic models to improve prediction and inference in emerging epidemics,"PROJECT SUMMARY When an outbreak of an established or emerging infectious disease occurs we ask a standard set of questions that are critical to a lifesaving public health response: Where will future incidence occur? How many cases will there be? And where can we most effectively intervene? The proposed research is motivated by real world instances where answering these questions was critical to making practical public health decisions, and current methods came up short: from deciding if and where to build additional Ebola Treatment Units in the 2014-15 West African Ebola epidemic, to identifying priority districts where oral cholera vaccine should be used in the 2016-17 cholera outbreak in Yemen, to picking locations where sufficient cases might occur to selecting and prioritizing interventions to slow the spread of COVID-19 worldwide. Forecasts informing such decisions are typically generated either using an epidemic model that relies on knowledge of the disease transmission mechanism and epidemic theory or using a statistical model to project the expected number of cases based on the relationship between covariates and observed counts. However, both approaches are subject to limitations, particularly early in an epidemic when few cases are observed. This project is based on the overarching scientific premise that inferences that combine the strengths of mechanistic epidemic models and statistical covariate models will substantially outperform either approach alone in forecasting and making decisions to confront emerging infectious disease threats. Specifically, this project aims to (1) Develop a framework to forecast incidence in ongoing outbreaks that merges mechanistic and machine learning approaches; (2) Validate the framework using retrospective data and apply the framework to inform decision making in emerging epidemics; (3) Integrate this inferential forecasting framework into causal decision theory to optimize critical actions in the public health response to emerging epidemics; and (4) Develop accessible and extensible tools for forecasting and decision analysis in infectious disease epidemics. We will validate these approaches using rigorous simulation studies and by applying the proposed approaches to retrospective data from important recent epidemics (e.g., Ebola, Cholera and COVID-19, as mentioned above). We will prospectively apply our approach to inform the response to emerging disease threats that occur during the project period, including the ongoing COVID-19 pandemic. To ensure that the tools developed are useful, efficient, and user friendly, we will work with international humanitarian organizations responding to epidemics. Successful completion of these aims will provide a flexible and validated framework for forecasting and decision making during ongoing epidemics, while allowing for innovation in mechanistic and statistical approaches. In doing so it will provide tools to optimize responses and reduce morbidity and mortality during public health crises.",,2021,Johns Hopkins University,92287,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P23258,5R21AI142638-02,A VSV vectored vaccine for emergent tick-born phleboviruses,"Vesicular stomatitis virus (VSV) is a cytopathic virus that has been developed as a vaccine vector due to its ability to induce strong, protective antibody and T cell responses to encoded foreign antigens after a single dose. VSV efficiently incorporates glycoproteins ( GP) from a different virus on virion surface allowing production of replication-competent recombinant vectors in which the cognate VSV G gene is replaced by a foreign GP gene. Recombinant VSVs (rVSVs) expressing foreign GPs have been studied as vaccine vectors for a number of pathogens including the recent successful deployment of a rVSV-Ebola vaccine. Despite this success, studies in animal models demonstrate significant pathogenic effects when some rVSV are injected intracerebrally or when used to infect animals with defective interferon responses. Concerns raised by these studies support development of more attenuated rVSV vectors with better safety profiles. Specific Aim 1 will utilize a novel strategy for attenuating rVSV vaccine vectors by joining adjacent VSV transcripts using a P2A ribosomal skipping sequence between adjacent genes in the VSV genome. rVSV with single or multiple fused transcripts will be tested for pathogenesis in immunocompromised mouse models or in the CNS. In Specific Aim 2 these next generation, low pathogenicity vectors expressing the glycoproteins of Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) will be analyzed for their ability to induce neutralizing responses. SFTSV is a pathogenic, tick-transmitted bunyaviruses that causes a severe febrile hemorrhagic-like disease with case fatality rates of up to 30%. Initially discovered during a 2009 outbreak of febrile illness in China, the geographic distribution of SFTSV extends into Korea and Japan. There are currently no vaccine or therapeutics for SFTSV. Because of its potential threat the WHO included SFTSV in its 2017 recommendation “A research and development Blueprint for action to prevent epidemics” and identified SFTSV as one of 11 pathogens most likely to cause severe outbreaks in the near future and proposed development of vaccines. Included in this revised application are preliminary data demonstrating induction of strong neutralizing antibody responses that correlate with protection from SFTSV challenge in mice vaccinated with a 1st generation rVSV-SFTSV. Additionally, vaccination of IFNAR-/- mice with the 1st generation rVSV-SFTSV demonstrated significant pathology (weight loss) supporting the premise for Aim 1. This short IDEA proposal is designed to produce attenuated rVSV vectors useful for vaccine development for many pathogens and will generate proof-of-principle data that will permit further development of a vaccine for SFTSV.",,2023,University Of Pennsylvania,202917,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P23260,5R25TW011505-02,United States-Mali Research Ethics Training Program (US-Mali RETP),"Project Summary/Abstract The past four decades, have witnessed a significant increase in public health and clinical research being conducted in Mali, driven partly by increasing international research collaborations and the recent Ebola epidemic. This increase in human research, creates an urgent need for improved bioethics leadership, training, policy and research. It is, therefore, critical and timely to ensure that researchers and members of institutional review board (IRB) in Mali have the requisite knowledge, and capacity to ensure the research meets ethical, cultural, and regulatory expectations. To meet the ethics training needs of Mali, we propose a research ethics capacity building program to strengthen research ethics education and research in Mali through an innovative model of sustainable capacity development to prepare the next generation of ethics researchers. This program will be based on close collaboration between two institutions â€Â"" the George Washington University Milken Institute School of Public Health (GWU), USA and University of Science, Techniques & Technologies of Bamako (USTTB), Mali. The overall goal of the United States-Mali Research Ethics Training Program (US-Mali RETP) is to strengthen research ethics education and research in Mali. Our model will focus on using US and Africa-based expertise to strengthen USTTB’s capacity to develop and lead a new Master’s degree specialization in research ethics and promote a sustainable bioethics enterprise at USTTB through the following specific aims; Specific Aim 1: To enhance the pedagogical and curricular strengths of key USTTB faculty to deliver research ethics courses and mentoring in Mali. We will implement a faculty development program for selected Malian faculty aimed at enhancing analytical capacity in ethics research and training. The selected Malian faculty will participate in intensive courses in US, work with GWSPH faculty in developing curricula and co-delivery of ethics curriculum during year 2. Specific Aim 2: To develop a research ethics specialization within the existing USTTB Masters of Public Health (MPH) program in order to train a core group of professionals with expertise in research ethics in Mali. We will develop a new curriculum in research ethics within the MPH program at USTTB. The Ethics modules will also be offered as part of a one year Diplome. We will also offer short term training workshops and webinars at USTTB including both basic and advanced topics each year. Specific Aim 3: To promote research around key priorities for research ethics in Mali. We will through our trainees conduct relevant national research on ethics to inform public health, training priorities and health care delivery including ethics of research on infectious and emerging diseases as well as genetics and genomics. Specific Aim 4: To create a dedicated “Research Ethics Unit” within USTTB in Mali. We will work to establish an academic Research Unit within USTTB which will coordinate Bioethics research and activities at USTTB and enhance sustainability of our efforts. This unit will also coordinate a national forum to discuss research ethics in Mali in collaboration with the Ministry of Health (MoH) in Mali.",,2024,George Washington University,242379,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,,2020 +P23264,7R01GM140564-02,Merging machine learning and mechanistic models to improve prediction and inference in emerging epidemics,"PROJECT SUMMARY When an outbreak of an established or emerging infectious disease occurs we ask a standard set of questions that are critical to a lifesaving public health response: Where will future incidence occur? How many cases will there be? And where can we most effectively intervene? The proposed research is motivated by real world instances where answering these questions was critical to making practical public health decisions, and current methods came up short: from deciding if and where to build additional Ebola Treatment Units in the 2014-15 West African Ebola epidemic, to identifying priority districts where oral cholera vaccine should be used in the 2016-17 cholera outbreak in Yemen, to picking locations where sufficient cases might occur to selecting and prioritizing interventions to slow the spread of COVID-19 worldwide. Forecasts informing such decisions are typically generated either using an epidemic model that relies on knowledge of the disease transmission mechanism and epidemic theory or using a statistical model to project the expected number of cases based on the relationship between covariates and observed counts. However, both approaches are subject to limitations, particularly early in an epidemic when few cases are observed. This project is based on the overarching scientific premise that inferences that combine the strengths of mechanistic epidemic models and statistical covariate models will substantially outperform either approach alone in forecasting and making decisions to confront emerging infectious disease threats. Specifically, this project aims to (1) Develop a framework to forecast incidence in ongoing outbreaks that merges mechanistic and machine learning approaches; (2) Validate the framework using retrospective data and apply the framework to inform decision making in emerging epidemics; (3) Integrate this inferential forecasting framework into causal decision theory to optimize critical actions in the public health response to emerging epidemics; and (4) Develop accessible and extensible tools for forecasting and decision analysis in infectious disease epidemics. We will validate these approaches using rigorous simulation studies and by applying the proposed approaches to retrospective data from important recent epidemics (e.g., Ebola, Cholera and COVID-19, as mentioned above). We will prospectively apply our approach to inform the response to emerging disease threats that occur during the project period, including the ongoing COVID-19 pandemic. To ensure that the tools developed are useful, efficient, and user friendly, we will work with international humanitarian organizations responding to epidemics. Successful completion of these aims will provide a flexible and validated framework for forecasting and decision making during ongoing epidemics, while allowing for innovation in mechanistic and statistical approaches. In doing so it will provide tools to optimize responses and reduce morbidity and mortality during public health crises.",,2024,UNIV OF NORTH CAROLINA CHAPEL HILL,357821,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P23265,5DP1AI158124-02,A functional evolutionary genetic approach to combat viral infection,"Project Summary Humans are under increasing threat from viruses that spill over from animal reservoirs. Most of these viral diseases lack targeted treatments. We speculate that this unmet medical need might be addressable by first understanding the evolutionary principles underlying antiviral immune responses. A major component of innate immunity in mammals is the interferon response. Interferon induces hundreds of genes, many of which encode effector proteins that suppress viral infection. In mammals, these antiviral effectors are rapidly evolving, most likely in response to the genetic ""arms race"" continually occurring between virus and host. Further, certain mammalian orders, such as primates, rodents, bats, and carnivores, are particularly rich in viruses that have the potential to spill over into humans. We hypothesize that the genomes of these viral zoonotic reservoirs encode unique antiviral effectors that may be harnessed to combat human viral pathogens. The goals of this project are to identify, characterize, and validate the efficacy of novel antiviral proteins from diverse non-model mammalian species. State-of-the-art genetic screening platforms will be used to discover antiviral genes in primary cell cultures obtained from multiples species in the following mammalian orders: Primate, Rodentia, Chiroptera, and Carnivora. Validated effectors will be characterized mechanistically with a suite of virological, biochemical, molecular, and cell biological approaches. The potential for these effectors to suppress human viruses will be tested in murine models of human viral disease. Outcomes will include the creation of the first comprehensive Mammalian Antiviral Protein Atlas, the discovery of new genetically-encoded antiviral mechanisms, and proof-of- concept that human viral disease can be thwarted by naturally occurring proteins from other species. The impact of this proposal will be the development of a new area of biomedical research at the intersection of virology, immunology, and evolutionary biology. Long term prospects include harnessing the results of these studies to inspire alternative approaches to antiviral drug development.",,2025,UT SOUTHWESTERN MEDICAL CENTER,1147708,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P23275,5R01AI151176-02,"Accelerating viral outbreak detection in US cities using mechanistic models, machine learning and diverse geospatial data","Project Abstract/Summary Our interdisciplinary research team will develop algorithms to accelerate the detection of respiratory virus outbreaks at an unprecedented local scale in US cities. We propose to advance outbreak detection by combining machine learning data integration methods and spatial models of disease transmission. The dynamic models that will be developed will provide mechanistic engines for distinguishing typical from atypical disease trends and the optimization methods evaluate the informativeness of data sources to achieve specified public health goals through the rapid evaluation of diverse input data sources. Working with local healthcare and public health leaders, we will translate the algorithms into user-friendly online tools to support preparedness plans and decision-making. Our proposed research is organized around three major aims. In Aim 1, we will apply machine learning and signal processing methods to build systems that track the earliest indicators of emerging outbreaks within seven US cities. We will evaluate non-clinical data reflecting early and mild symptoms as well as clinical data covering underserved communities and geographic and demographic hotspots for viral emergence. In Aim 2, we will develop sub-city scale models reflecting the syndemics of co-circulating respiratory viruses and chronic respiratory diseases (CRD) that can exacerbate viral infections. We will infer viral transmission rates and socio-environmental risk cofactors by fitting the model to respiratory disease data extracted from millions of electronic health records (EHRs) for the last nine years. We will then partner with clinical and EHR experts to translate our models into the first outbreak detection system for severe respiratory viruses that incorporates EHR data on CRDs. Using machine learning techniques, we will further integrate other surveillance, environmental, behavioral and internet predictor data sources to maximize the accuracy, sensitivity, speed and population coverage of our algorithms. In Aim 3, we will develop an open-access Python toolkit to facilitate the integration of next generation data into outbreak surveillance models. This project will produce practical early warning algorithms for detecting emerging viral threats at high spatiotemporal resolution in several US cities, elucidate socio-geographic gaps in current surveillance systems and hotspots for viral emergence, and provide a robust design framework for extrapolating these algorithms to other US cities.",,2025,Yale University,596017,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P23276,3UM1AI148689-02S1,Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2022,University Of Maryland Baltimore,2095587,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2020 +P23277,3UM1AI148689-02S5,UMB Vaccine Treatment Evaluation Unit - DMID21-0004,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2024,University Of Maryland Baltimore,667476,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,Unspecified,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Clinical trial (unspecified trial phase),2021 +P23278,3UM1AI148689-02S2,VTEU Supplement,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2021,University Of Maryland Baltimore,5179983,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Not applicable,,Filoviridae,,,,,,,,,Ebola virus disease | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Therapeutic trial design | Vaccine trial design and infrastructure,2021 +P23279,3UM1AI148689-02S3,Vaccine Treatment Evaluation Units(VTEU) mRNA-1273-P204 Moderna Pediatric,"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding.",,2022,University Of Maryland Baltimore,1585845,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,Unspecified,Novel Pathogen,,,,,,,,,Pandemic-prone influenza | Disease X | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Diagnostics,2021 +P23280,1R01AI150888-01A1,A Fully Integrated Point-of-Care Test for Ebola,"PROJECT SUMMARY The objective of this proposal is to develop a new point-of-care test (POCT)â€Â""the D4 assayâ€Â""for early field- detection of Ebola virus (EBOV) infection. Currently, EBOV is diagnosed by RNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR requires a makeshift BSL-4 grade laboratory in the field, expensive equipment, and highly trained personnel. Other POCTs, including the user-friendly lateral-flow assay (LFA), lack the sensitivity for early detection that is critical for timely intervention with the available antibody cocktail that yields 90% survival rates for patients with low viremia. Our objective is motivated by an urgent clinical need for a POCT that (1) detects EBOV infection in the field quickly and reliably, (2) requires little on-field infrastructure, (3) yields results in 30 min, and (4) matches or exceeds the performance of RT-PCR. To achieve these goals, we have designed an integrated POCT the D4 assay that has four simple stepsâ€Â""dispense, dissolve, diffuse, and detect that require limited handling and skill to perform. This new-frontier technology takes advantage of the presence of an unmistakable, viral secreted glycoprotein sGP that is present in the serum of infected patients very early in infection. We have generated customized monoclonal antibodies (Abs) for sGP to use in the D4 assay. The current prototype D4 assay that we have designed detects EBOV infection at least one day earlier than RT-PCR in infected monkeys and at a far lower cost than RT-PCR or LFA. In this proposal, we plan to advance our development and improve the sensitivity of the D4 assay further as well as reduce the assay time from 60 min to 30 min. Our strategy is to increase the equilibrium binding constant of our current Ab pair from ~10-9 M to ~10-11 M with antibody affinity maturation techniques and high-throughput screening of antibody pairs. The enhanced D4 assay kit will have inkjet-printed capture and detection antibodies on a protein and cell-resistant polymer brush on a glass plate encased in a passive capillarity microfluidics chip. The assay output will be fluorescence of microspots on the D4 chip. We have developed a portable handheld fluorescence detector to capture and image the spots and automatically convert them into the concentration of analytes for quantitation and uploaded to a secure server. The design will be rigorously tested and validated with samples from infected human cells and laboratory-challenged non-human primates. At the completion of this project, we will have a field-ready, user-friendly, and highly sensitive POCT that will allow healthcare workers to detect EBOV in serum, blood, or other bodily fluids in 30 min. The new design will push the current boundaries of EBOV detection and facilitate more expedient deployment of infection control and patient support measures that can yield 90% survival rates or better if implemented early in infection. Because the D4 POCT is multiplexable, it will set a precedent for broader utility beyond EBOV to diagnose many other infectious diseases.",,2025,Duke University,717426,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23281,1R01AI148784-01,Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variant,"The 2013â€Â""2016 Ebola virus (EBOV) disease epidemic was orders of magnitude larger than any previous EBOV outbreak. Preliminary data indicate that GP-A82V, an EBOV glycoprotein mutant that came to dominate the outbreak, increases infectivity in human cells. To elucidate the mechanism by which GP-A82V increases infectivity, and to clarify its significance for Ebola virus replication and transmission, we have assembled a team that leverages NIAID resources at the IRF-Fort Detrick and the Genomic Center for Infectious Diseases at The Broad Institute. Aim 1 will be to investigate the mechanism by which GP-A82V increases virion fusogenicity. Computer modeling suggests that GP-A82V destabilizes glycoprotein conformation. Mutations engineered based on the models will be tested for effects on infectivity, the reorganization of critical interactions as determined by molecular dynamics simulations, conformational equilibrium as determined by smFRET, novel assays for GP fusion, Cryo-EM of GP trimers, and crystal complexes with the NPC1 C-loop. Aim 2 will be to assess the effect of GP-A82V in the context of the EBOV Makona variant on infectivity in human cells in vitro and in humanized mice. We will generate a reverse genetic system for the ancestral EBOV Makona lineage and test the effect of GP-A82V on this background. Replication of WT and GP-A82V will be compared in U20S cells, in human dendritic cells, and in a novel humanized mouse model where the effect of GP-A82V on virus sequence adaptation to specific tissue compartments will be assessed. From these experiments we expect to clarify the significance of GP-A82V for viral replication and transmission, taking into account the genetic background of the EBOV and the species-specific effects of GP-A82V. Aim 3 will be to examine the effect of GP-A82V on neutralizing antibodies. Preliminary data indicate that GP-A82V is relatively resistant to neutralization by particular antibodies. Using a panel of monoclonal antibodies targeting different parts of GP, we will determine whether neutralization resistance is a general property of GP-A82V, or if this trait is specific to antibodies targeting particular regions of GP. If differential neutralization is observed with particular antibodies, the effect of these on viral titer will be tested in the humanized mouse model. We will also determine whether GP-A82V alters neutralization sensitivity to convalescent sera from Guineans infected early or later in the outbreak, and from individuals treated at Emory University. From these studies we hope to determine whether the antibody response to EBOV was different depending on whether a person was infected with virus bearing GP-A82 or GP-A82V. If differences in neutralization titer correlate with virus genotype it would contribute to understanding the factors that determine survival in an infected individual or the efficiency of transmission to people who come into contact with infected body fluids. Finally, these studies will provide valuable experimental tools that will inform our studies on GP structure and function.",,2024,UNIV OF MASSACHUSETTS MED SCH WORCESTER,836194,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P23282,1R21AI142638-01A1,A VSV vectored vaccine for emergent tick-born phleboviruses,"Vesicular stomatitis virus (VSV) is a cytopathic virus that has been developed as a vaccine vector due to its ability to induce strong, protective antibody and T cell responses to encoded foreign antigens after a single dose. VSV efficiently incorporates glycoproteins ( GP) from a different virus on virion surface allowing production of replication-competent recombinant vectors in which the cognate VSV G gene is replaced by a foreign GP gene. Recombinant VSVs (rVSVs) expressing foreign GPs have been studied as vaccine vectors for a number of pathogens including the recent successful deployment of a rVSV-Ebola vaccine. Despite this success, studies in animal models demonstrate significant pathogenic effects when some rVSV are injected intracerebrally or when used to infect animals with defective interferon responses. Concerns raised by these studies support development of more attenuated rVSV vectors with better safety profiles. Specific Aim 1 will utilize a novel strategy for attenuating rVSV vaccine vectors by joining adjacent VSV transcripts using a P2A ribosomal skipping sequence between adjacent genes in the VSV genome. rVSV with single or multiple fused transcripts will be tested for pathogenesis in immunocompromised mouse models or in the CNS. In Specific Aim 2 these next generation, low pathogenicity vectors expressing the glycoproteins of Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) will be analyzed for their ability to induce neutralizing responses. SFTSV is a pathogenic, tick-transmitted bunyaviruses that causes a severe febrile hemorrhagic-like disease with case fatality rates of up to 30%. Initially discovered during a 2009 outbreak of febrile illness in China, the geographic distribution of SFTSV extends into Korea and Japan. There are currently no vaccine or therapeutics for SFTSV. Because of its potential threat the WHO included SFTSV in its 2017 recommendation “A research and development Blueprint for action to prevent epidemics” and identified SFTSV as one of 11 pathogens most likely to cause severe outbreaks in the near future and proposed development of vaccines. Included in this revised application are preliminary data demonstrating induction of strong neutralizing antibody responses that correlate with protection from SFTSV challenge in mice vaccinated with a 1st generation rVSV-SFTSV. Additionally, vaccination of IFNAR-/- mice with the 1st generation rVSV-SFTSV demonstrated significant pathology (weight loss) supporting the premise for Aim 1. This short IDEA proposal is designed to produce attenuated rVSV vectors useful for vaccine development for many pathogens and will generate proof-of-principle data that will permit further development of a vaccine for SFTSV.",,2022,University Of Pennsylvania,243000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P23283,3U45ES019360-10S2,Hazardous Waste Worker Training Program (HWWTP),"The Texas-Utah Consortium for Hazardous Waste Worker Education and Training (The Consortium) leverages two large established education and research centers, both funded in part by the National Institute for Occupational Safety and Health, with a diverse and experienced collection of partners to develop and deliver a full spectrum of high quality education, research and training. The Consortium’s primary purpose is to positively and meaningfully impact the health of our communities by providing practical hands-on health and safety training to workers and by placing special emphasis on training returning veterans and members of underserved minorities. In the Hazardous Waste Worker Training Program we will target hazardous material workers who are, or will be, engaged in the generation, management, analysis, treatment, storage, transportation (including loading and unloading), disposal, emergency response, clean up and remediation of hazardous materials and wastes. Our specific aims are to train workers to identify and prevent hazardous exposures to themselves, their colleagues, their community and the environment by utilizing our resources and partners to deliver high quality education and training in the following areas: Hazardous Waste Operations and Emergency Response (HAZWOPER) standard, the US Department of Transportation Hazardous Materials Regulations, Certified Fire Inspector, Hazardous Materials Management, and other timely and impactful health and safety courses, such as Ebola Prevention Training for University Personnel.",,-99,University Of Texas Hlth Sci Ctr Houston,27997,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Other,Not applicable,,Filoviridae,,,,,,,,,Ebola virus disease,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Infection prevention and control,,2020 +P23284,1DP1AI158125-01,"Creating high-resolution, epitope-focused vaccines","PROJECT SUMMARY / ABSTRACT The long-term objective of the research proposed here is to establish a novel method for creating vaccines. These vaccines will lead to a highly focused antibody response toward particular epitopes that are known to be the targets of neutralizing monoclonal antibodies (mAbs). If successful, this approach could be applied broadly for the creation of important, new vaccines that protect against infectious disease. The ability to focus the antibody response toward particular epitopes would permit vaccines to be created that elicit neutralizing antibodies, instead of non-neutralizing antibodies. It would also permit creation of vaccines that lead to an antibody response directed against highly conserved regions of an infectious agent, leading to broad spectrum protection against different strains and minimizing the possibility of “escape” by mutant variants. The key starting material for the approach is a mAb that is broadly neutralizing against the infectious agent. In recent decades, many potent, broadly neutralizing mAbs (bnAbs) have been isolated and characterized in detail. Some of these bnAbs (for example, that target influenza virus, Ebola virus and HIV-1) have entered clinical trials to test their efficacy in treating infectious disease and/or to determine whether passively infused mAb can prevent infection. Despite major research funding, however, it has generally not been possible to create vaccines that are capable of eliciting antibodies with properties such as these bnAbs. Here, a simple but radically different approach for creating epitope-focused vaccine candidates is utilized that leverages a tool that has been available all along â€Â"" the mAb itself. First, binding of the mAb is used to protect the target epitope. Next the surface of the remainder of the antigen is modified to render it non-immunogenic. Finally, the protecting mAb is removed, thereby deprotecting and exposing the unmodified, target epitope. The method is called protect, modify, deprotect (or PMD). Ultimately, this high-risk, high-reward proposal could enable creation of vaccines that elicit an antibody response against any given mAb epitope, and only that epitope.",,2025,Stanford University,1103900,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Pandemic-prone influenza | Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2020 +P23285,3D71TW010434-01A1S1,Sustainable Research Training and Capacity Building in Liberia for Emerging Viral Epidemics,"PROJECT SUMMARY/ABSTRACT Liberia, a resource rich but economically poor country, continues to struggle with growth and recovery following its 14-year civil war that destroyed its infrastructure. During the recent Ebola virus (EBOV) epidemic, Liberia had fewer than 100 physicians and needed help from the international community for its control. The assistance Liberia received largely improved physical resources (e.g., laboratory equipment and containment facilities), but did not significantly increase human resources. Today, the healthcare workforce has only ~25% of the nurses, midwives, and pharmacists, and 9% of the physicians the country needs. For Liberia to develop sustainable research capacity for early identification and control of emerging viral diseases with the potential for regional and global pandemics, Liberia needs a mechanism to garner students’ interest, and a continuous supply of university-educated students graduating with current knowledge on viruses, epidemiology and how to conduct research. The University of Liberia (UL) is the largest government supported institution in Liberia, and its College of Science and Technology awards Bachelor of Science degrees to students who wish to enter the health professions. Also, UL’s College of Medicine and Tubman Institute of Medicinal Arts train physicians and nurses, respectively. In 2015, UL conducted a needs assessment and developed a strategic academic plan. In response to this plan, faculty in the Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai’i (UH), and the University of Yaoundé 1 (UY) propose to partner with faculty at UL to establish a creative training program with the goal of garnering interest and improving teaching and student learning experience in biomedical sciences at UL, and providing training in the conduct of research on emerging viral epidemics. The planning process has 12 steps: 1) devise a career development plan for faculty; 2) determine how to strengthen the curriculum in virology, emerging epidemic diseases, and research; 3) assess feasibility of long-distance learning between UL and UH; 4) evaluate the possibility of introducing a laboratory-based course entitled “Research on Emerging Epidemic Viruses,” into the curriculum; 5) identify opportunities for students to participate in in-country mentored research projects; 6) investigate other activities for inclusion in a training grant; 7) explore training of Liberian students in Hawai’i; 8) establish south-south academic and research collaboration; 9) identify a method for selecting students for training; 10) assess needs for specific skilled personnel in the Liberian healthcare workforce; 11) identify individuals with multi-disciplinary backgrounds to serve on a Training Advisory Group; and 12) write a D43 application. The ten-person planning committee consists of UL, UH and UY faculty who are teacher-scholars, and their D71 planning efforts are supported by a larger group of faculty with experience in virology, epidemiology and global health research. Strengthening the research capacity at the UL is the only way to guarantee a sustainable cadre of health professionals with research expertise to identify and control future emerging viral epidemics in Liberia.",,2021,University Of Hawaii At Manoa,21600,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Filoviridae | Unspecified,,,,,,,,,Ebola virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P23287,1R25TW011505-01,United States-Mali Research Ethics Training Program (US-Mali RETP),"Project Summary/Abstract The past four decades, have witnessed a significant increase in public health and clinical research being conducted in Mali, driven partly by increasing international research collaborations and the recent Ebola epidemic. This increase in human research, creates an urgent need for improved bioethics leadership, training, policy and research. It is, therefore, critical and timely to ensure that researchers and members of institutional review board (IRB) in Mali have the requisite knowledge, and capacity to ensure the research meets ethical, cultural, and regulatory expectations. To meet the ethics training needs of Mali, we propose a research ethics capacity building program to strengthen research ethics education and research in Mali through an innovative model of sustainable capacity development to prepare the next generation of ethics researchers. This program will be based on close collaboration between two institutions â€Â"" the George Washington University Milken Institute School of Public Health (GWU), USA and University of Science, Techniques & Technologies of Bamako (USTTB), Mali. The overall goal of the United States-Mali Research Ethics Training Program (US-Mali RETP) is to strengthen research ethics education and research in Mali. Our model will focus on using US and Africa-based expertise to strengthen USTTB’s capacity to develop and lead a new Master’s degree specialization in research ethics and promote a sustainable bioethics enterprise at USTTB through the following specific aims; Specific Aim 1: To enhance the pedagogical and curricular strengths of key USTTB faculty to deliver research ethics courses and mentoring in Mali. We will implement a faculty development program for selected Malian faculty aimed at enhancing analytical capacity in ethics research and training. The selected Malian faculty will participate in intensive courses in US, work with GWSPH faculty in developing curricula and co-delivery of ethics curriculum during year 2. Specific Aim 2: To develop a research ethics specialization within the existing USTTB Masters of Public Health (MPH) program in order to train a core group of professionals with expertise in research ethics in Mali. We will develop a new curriculum in research ethics within the MPH program at USTTB. The Ethics modules will also be offered as part of a one year Diplome. We will also offer short term training workshops and webinars at USTTB including both basic and advanced topics each year. Specific Aim 3: To promote research around key priorities for research ethics in Mali. We will through our trainees conduct relevant national research on ethics to inform public health, training priorities and health care delivery including ethics of research on infectious and emerging diseases as well as genetics and genomics. Specific Aim 4: To create a dedicated “Research Ethics Unit” within USTTB in Mali. We will work to establish an academic Research Unit within USTTB which will coordinate Bioethics research and activities at USTTB and enhance sustainability of our efforts. This unit will also coordinate a national forum to discuss research ethics in Mali in collaboration with the Ministry of Health (MoH) in Mali.",,2024,George Washington University,247318,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Unspecified,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in Governance,2020 +P23290,272201600013C-P00012-9999-12,MICROBIOLOGY AND INFECTIOUS DISEASES BIOLOGICAL RESEARCH REPOSITORY (MID BRR),"This contract provides unique and quality-assured infectious reagents and resources to the scientific community for use in basic research and product development. The scope of this contract includes the acquisition, authentication, production, preservation, storage, and distribution of research and reference reagents to the research community. These reagents span the pathogens in the Division of Microbiology and Infectious Diseases portfolio, and include the National Institutes of Allergy and Infectious Disease (NIAID) Category A, B and C Priority Pathogens and emerging infectious diseases.",,2020,AMERICAN TYPE CULTURE COLLECTION,508767,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P23291,1DP1AI158124-01,A functional evolutionary genetic approach to combat viral infection,"Project Summary Humans are under increasing threat from viruses that spill over from animal reservoirs. Most of these viral diseases lack targeted treatments. We speculate that this unmet medical need might be addressable by first understanding the evolutionary principles underlying antiviral immune responses. A major component of innate immunity in mammals is the interferon response. Interferon induces hundreds of genes, many of which encode effector proteins that suppress viral infection. In mammals, these antiviral effectors are rapidly evolving, most likely in response to the genetic ""arms race"" continually occurring between virus and host. Further, certain mammalian orders, such as primates, rodents, bats, and carnivores, are particularly rich in viruses that have the potential to spill over into humans. We hypothesize that the genomes of these viral zoonotic reservoirs encode unique antiviral effectors that may be harnessed to combat human viral pathogens. The goals of this project are to identify, characterize, and validate the efficacy of novel antiviral proteins from diverse non-model mammalian species. State-of-the-art genetic screening platforms will be used to discover antiviral genes in primary cell cultures obtained from multiples species in the following mammalian orders: Primate, Rodentia, Chiroptera, and Carnivora. Validated effectors will be characterized mechanistically with a suite of virological, biochemical, molecular, and cell biological approaches. The potential for these effectors to suppress human viruses will be tested in murine models of human viral disease. Outcomes will include the creation of the first comprehensive Mammalian Antiviral Protein Atlas, the discovery of new genetically-encoded antiviral mechanisms, and proof-of- concept that human viral disease can be thwarted by naturally occurring proteins from other species. The impact of this proposal will be the development of a new area of biomedical research at the intersection of virology, immunology, and evolutionary biology. Long term prospects include harnessing the results of these studies to inspire alternative approaches to antiviral drug development.",,2025,UT SOUTHWESTERN MEDICAL CENTER,1144500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P23292,1R15GM139070-01,Mechanism of Interaction between Influenza Hemagglutinin and Host Cell Phosphoinositides,"Influenza virus causes significant illness and mortality in the U.S. and worldwide. Vaccines offer some protection, but must be continuously tailored to seasonal mutations of the virus. Some strains of influenza are resistant to one or more of the limited number of available anti-viral drugs. New strategies which attack invariant features of the virus are desperately needed. The protein hemagglutinin, found on the surface of the virus, allows the virus to bind to host cells and enter. Entry depends on high density clusters of hemagglutinin within the viral membrane, but the mechanism of cluster formation is unknown. This project will address the fundamental question of how hemagglutinin forms clusters, even in the absence of other viral components, by hijacking cellular components. We recently discovered that hemagglutinin interacts with a particular host cell lipid (PIP2) that is able to control the host cell cytoskeleton and several signaling pathways that have been implicated previously in infection. This project will investigate the mechanism of interaction between hemagglutinin and PIP2 using super- resolution microscopy and other fluorescence methods, targeting the portions of hemagglutinin that are invariant and therefore less likely to mutate over time. Results will help identify new targets for anti-viral drugs and illuminate how influenza is able to modify the host cell cytoskeleton and plasma membrane for its own life cycle.",,2024,University Of Maine Orono,428192,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P23293,1R43IP001142-01,"Nanotrap particle viral enrichment technology for enabling portal, next-generation sequencing-based surveillance","PROJECT SUMMARY RNA viruses, such as influenza and the Ebola virus, have been classified as the greatest threat for causing a global pandemic given their high mutation rates and abilities to jump between host species. National and global agencies have called for research and development efforts to improve RNA virus surveillance capabilities. While the tools for surveilling DNA viruses have advanced dramatically over the last two decades, the unique properties of RNA viruses have thwarted attempts to develop similar surveillance tools for them. Current state-of-the-art screening methods, like RT-qPCR and genome sequencing, require heavy equipment and wet-lab facilities, which has hindered progress of field-deployable surveillance and monitoring practices by federal agencies, such as the Centers for Disease Control’s Influenza Genomics Team (IGT). Furthermore, pathogen loads from biological samples decay rapidly over an infection’s course, decreasing below detectable levels only days after symptoms appear. Thus, there is a need to define new protocols and devices for RNA virus sample enrichment that combine speed, cost-effectiveness, ease of use, and the capacity for field operation. This need is underscored by early field work by the IGT, which utilized a potential new field-deployable viral surveillance sequencing protocol but demonstrated that the sensitivity and specificity of this protocol is lacking. Collaborations between the IGT and the applicant, Ceres Nanosciences, has led to the current SBIR Phase I initiative, aimed at testing the feasibility of leveraging Ceres’ innovative nanoparticle technology, termed Nanotrap (NT), as a companion virus enrichment device that is inexpensive, easy-to-use, and rapid enough to integrate prior to the use of RNA and DNA viral sequencing tools recently developed by the CDC and other organizations. The major technical objective now is to transition this work into a portable device that can be used to enrich viruses from samples collected in the field, so that it can be used in coordination with field-deployable viral sequencing tools. This work will be accomplished through the following specific aims over a nine-month project period: Aim 1 will demonstrate the feasibility of using NT particles to capture and concentrate influenza pathogens from low-titer (<30 ct), contrived viral transport media (VTM) samples and improve MinION sensitivity; Aim 2 will test the performance characteristics of using the NT-enabled pre-enrichment step prior to genomic sequencing to detect the presence of respiratory pathogens. The importance of this work would be the generation of a technology to significantly improve the rapid identification and characterization of known and novel strains of RNA or DNA viruses circulating in samples collected from the field. The long-term commercial product resulting from this work would be an optimized, validated, field-deployable virus enrichment device that would be marketed for use by the CDC, USDA, DHS, DoD, and any other laboratories that monitor RNA- or DNA-based infectious diseases.",,2021,"CERES NANOSCIENCES, LLLP",243500,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2020 +P23300,1U44AI152995-01,"A Randomized Phase I Clinical Trial of HydroVax-CHIKV, a Novel Inactivated Chikungunya Virus Vaccine","Chikungunya virus (CHIKV) is an alphavirus that has gained significant attention due to its ability to cause large epidemics among susceptible populations and to be spread beyond endemic countries by international travelers. Among a population of approximately 750,000 on the French island of La Reunion, 266,000 people were infected and over 200 CHIKV-related fatalities occurred during the 2006 outbreak. Likewise, an estimated 1.4 million people were infected with CHIKV in India during outbreaks that occurred from 2006 to 2007 and recently there have been more than 1.7 million people infected with CHIKV in the Caribbean and the Americas. At present, there is no commercial vaccine available for CHIKV. The development of an inactivated CHIKV vaccine suitable for immunizing the general population as well as vulnerable groups including infants and the elderly represents an important unmet clinical need. To address this critical unmet need, we have discovered a safe and immunogenic peroxide-inactivated chikungunya virus vaccine, HydroVax-CHIKV. Importantly, this advanced vaccine is safe and provides complete protection against infection and CHIKV-associated pathology in a robust mouse model. Here, we propose a double-blind, randomized, placebo-controlled Phase 1 dose escalation trial to evaluate the preliminary safety and immunogenicity of HydroVax-CHIKV. Our goal is to eventually provide vaccine coverage to vulnerable populations and the successful completion of this study will represent a key milestone in the advancement of a clinically relevant vaccine against chikungunya virus and provide a much- needed approach to protect the most susceptible members of society including infants, elderly, and those with potentially compromised immune functions.",,2022,"NAJIT TECHNOLOGIES, INC.",290420,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Flaviviridae,,,,,,,,,Other,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +P23303,1R01AI151176-01,"Accelerating viral outbreak detection in US cities using mechanistic models, machine learning and diverse geospatial data","Project Abstract/Summary Our interdisciplinary research team will develop algorithms to accelerate the detection of respiratory virus outbreaks at an unprecedented local scale in US cities. We propose to advance outbreak detection by combining machine learning data integration methods and spatial models of disease transmission. The dynamic models that will be developed will provide mechanistic engines for distinguishing typical from atypical disease trends and the optimization methods evaluate the informativeness of data sources to achieve specified public health goals through the rapid evaluation of diverse input data sources. Working with local healthcare and public health leaders, we will translate the algorithms into user-friendly online tools to support preparedness plans and decision-making. Our proposed research is organized around three major aims. In Aim 1, we will apply machine learning and signal processing methods to build systems that track the earliest indicators of emerging outbreaks within seven US cities. We will evaluate non-clinical data reflecting early and mild symptoms as well as clinical data covering underserved communities and geographic and demographic hotspots for viral emergence. In Aim 2, we will develop sub-city scale models reflecting the syndemics of co-circulating respiratory viruses and chronic respiratory diseases (CRD) that can exacerbate viral infections. We will infer viral transmission rates and socio-environmental risk cofactors by fitting the model to respiratory disease data extracted from millions of electronic health records (EHRs) for the last nine years. We will then partner with clinical and EHR experts to translate our models into the first outbreak detection system for severe respiratory viruses that incorporates EHR data on CRDs. Using machine learning techniques, we will further integrate other surveillance, environmental, behavioral and internet predictor data sources to maximize the accuracy, sensitivity, speed and population coverage of our algorithms. In Aim 3, we will develop an open-access Python toolkit to facilitate the integration of next generation data into outbreak surveillance models. This project will produce practical early warning algorithms for detecting emerging viral threats at high spatiotemporal resolution in several US cities, elucidate socio-geographic gaps in current surveillance systems and hotspots for viral emergence, and provide a robust design framework for extrapolating these algorithms to other US cities.",,2025,Yale University,611043,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P23304,1R43AI155185-01,Inhaled 'muco-trapping' antibody as universal immunotherapy for influenza virus infections,"Project Summary Seasonal infections from human influenza virus (INFV) represents a major public health burden. The flu vaccine only averts ~15% of medical visits and ~12% of hospitalizations due to INFV, whereas current antivirals are only modestly effective if given soon after symptoms emerge, which is achievable in only half of infected patients due to practical limitations in how quickly INFV infections can be diagnosed. Human monoclonal antibodies (mAb) delivered topically to mucosal surfaces offer exceptional promise as antivirals, combining safety, effectiveness and unparalleled specificity. Adding further to the promise of mAb, we have recently discovered a novel Ab function in mucus â€Â"" trapping individual pathogensâ€Â"" and have pioneered a technology enhancing the use of mAb in mucosal secretions based on carefully-tuned affinity between IgG-Fc and mucins, which has been exclusively licensed to Mucommune. Trapping pathogens in mucus prevents them from infecting target cells and spreading locally, facilitates rapid elimination from the airways, and enables effective protection in vivo. We believe the technology is uniquely suited to treat INFV infections, due to the unique pathophysiology of INFV. Studies have shown INFV to bud exclusively from the apical surface of epithelial cells. INFV also shares many pathological and clinical manifestations with Respiratory Syncytial Virus (RSV), which also sheds exclusively from the apical surface of infected cells and must traverse airway mucus (AM) before spreading to neighboring cells. This implies delivery of muco-trapping mAb into the airways can provide an immediate therapeutic benefit by trapping shed progeny virus in AM and facilitating their rapid clearance, unlike oral antivirals that have substantial delay in distribution to the lung. We have stably nebulized “muco-trapping” mAb to treat RSV infections in neonatal lambs, reducing the viral load by nearly 4-log by Day 6 post-infection after starting treatment as late as Day 3 post-infection. This motivated us to harness our platform to develop a “muco-trapping” mAb against INFV. In Aim 1, we will produce and characterize muco-trapping mAb against INFV, including their ability to bind and neutralize INFV. In Aim 2, working with IBT Biosciences (a CRO that specializes in animal models of infectious disease), we will assess whether muco-trapping mAb against INFV dosed intranasally can improve survival, clinical scores, and reduce lung viral titers relative to treatment with oseltamivir, the current gold standard of care, even after delayed treatment post-infection. Successful completion of these Phase I SBIR studies will lead to a Phase II proposal focused on mAb optimization, development of a nebulizable formulation, and efficacy/transmission studies in larger animal models. By enabling enhanced mAb functionality in mucus secretions, we expect Mucommune will help pave the way for improved, molecularly targeted therapies and prophylaxis against a broad spectrum of pathogens and microbes across all major mucosal surfaces.",,2022,"MUCOMMUNE, LLC",275437,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Institutes of Health (NIH),United States of America,Americas,Americas,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23305,109148,"Strengthening the regional science, technology, and innovation system in Central America","Countries in Central America who are members of the Sistema de la Integracion Centroamericana (SICA) continue to experience significant challenges in developing and implementing policies for science, technology, and innovation (STI), in addition to coordinating efforts in this sector to address issues of national and regional importance. In recent years there have been several efforts at the national and regional levels to support science 'Äî including extensive mapping of STI in Guatemala in collaboration with UNEducation and ScienceCO, bilateral collaborations with the European Union, and coordination efforts at the regional level 'Äî but important gaps remain. These gaps were discussed at an IDRC-sponsored workshop in May 2019 in Panama, where a roadmap and other activities to help advance STI in Central America were proposed. To start work on this roadmap and to develop previous capacity-building efforts, this project brings a consortium of key regional actors together, led by SICA, to work with science granting councils (or equivalent agencies) in member countries. The project will focus on strengthening the regional research system through a competitive call for seed funding and mobility in areas of regional priority; developing a long-term vision for inclusive STI in the region; supporting capacity building and reducing structural barriers to collaboration within the Commission for Science and Technology Development in Central America and Panama and in the region; and increasing the capacity of researchers to inform evidence-based public policies at the national and regional levels. This project aims to be a critical first step in catalyzing the efforts of national and regional bodies in support of science in Central America, and in demonstrating the value of these investments to governments, multilateral bodies, funders, and other key stakeholders in the region from the public, private, and non-profit sectors. The project has been adapted to account for and to contribute to addressing the COVID-19 situation in the region.",,2022,Sistema de Integración Centroamericana,324864,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,El Salvador,,,,2020 +P23307,109438,The Legal Empowerment Learning Agenda and Knowledge Hub,"The COVID-19 pandemic is altering the fabric of our societies and economies. While the full extent of its impact is not yet known, the disease and the response have disproportionately affected vulnerable populations in a wide range of areas, including access to justice. Some 1.5 billion people cannot access support to resolve their justice problems, such as denial of public services. Over half of the world'Äôs population (4.5 billion people) are affected to some degree by this growing justice gap. This has immediate impacts on individuals, including loss of livelihood, physical assets, and negative effects on mental and physical health. The situation is particularly acute for women and excluded groups 'Äî both a reflection and a driver of structural inequality and exclusion. In response to these challenges, this project will create a knowledge hub built around a shared learning agenda to determine how legal empowerment can contribute to democratic governance and overcoming the multi-dimensional obstacles to development. Activities will be designed with a view to co-generating comparative research findings through a range of peer-to-peer exchanges, skills support, and larger regional and global convenings of the Legal Empowerment Network. Those efforts are expected to improve the evidence base, research capacity, and methodologies on scaling up and deepening the impact of legal empowerment interventions. The knowledge hub and comparative lessons will spur greater awareness and action by governments, at both the national and global levels, on the urgency of addressing justice challenges within local and international development efforts.",,,"Namati, Inc.",1292392,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P23311,109459,Healthy food hubs: building sustainable and resilient agri-food systems in Lima and Quito,"COVID-19 has exposed the multidimensional connections between economic forces, public policies, and social inequalities. In Lima, Peru, and Quito, Ecuador, one of the main challenges authorities confronted in their response to the pandemic was providing food for millions of people while minimizing the risks of contagion. The pandemic revealed the lack of resilience of agri-food systems and related factors such as institutional and transportation limitations; disconnects between producers, authorities, and consumers; structural defects in commercial food chains; deficiencies in agroecological quality and healthy diets; and crowded marketplaces. This project will promote the development of municipal ""food hubs"" 'Äî local neighbourhood platforms composed of networks where food is exchanged between farmers, food markets, consumer groups, and other strategic stakeholders. Building on the efforts made by the two cities to promote sustainable agri-food systems, the project aims to strengthen the resilience and inclusiveness of urban and peri-urban agri-food systems to withstand pandemic, economic, and climate shocks by building an understanding of the interconnected drivers of production and access to healthy food. Using participatory action research, the project will generate scientific and social evidence to promote public policies that ensure nutritious food for vulnerable groups and enhance the resilience of local food markets. Activities include an assessment of current agri-food systems and identifying and improving best practices. The project will also assess food hubs as a novel policy response to enhance nutritional security. In the short term, it will help to improve the cities'Äô responses to the current challenges by engaging municipalities, farmers, and consumers in existing platforms.",,,Rikolto International s.o.n.,569010,Other,Not applicable,Not Applicable,Suburban Population/Setting | Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,Belgium,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +P23312,109469,Health systems strengthening through preparedness in COVID health emergency for refugees and IDPs in the West Bank,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis both in the short-term and longer-term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leverage local opportunities. This project will generate evidence to understand the effects of the COVID-19 pandemic on refugees and internally-displaced people in the West Bank and the health system'Äôs ability to meet their needs. It will also strengthen the health system through incorporating research and health information system strengthening. The methodology for this study will comprise three phases. There will be an initial rapid situation assessments and community engagement to analyze the pandemic response and engage with institutional and policy stakeholders. Next phase is larger scale quantitative and qualitative research activities followed by the translation of research for policy and practice to inform longer term preparedness and resilience of the health system. Throughout these stages, building capacities for research will be carried out, particularly in health system preparedness with regards to health human resources, health information system and community engagement. This project will lead to enhanced knowledge production both for short-term rapid response to COVID-19 as well as a longer-term participatory approach to pandemic preparedness and resilience from a gender and equity perspective for refugee and internally displaced populations. This COVID-19 health-focused initiative is part of the Centre-wide response to the current pandemic which includes other programmatic-focused responses and multi-programmatic ones. The health initiative will be approximately CAD 6 million which is part of the overall funds the Centre is allocating for COVID-19 programming.",,,Birzeit University,510304,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Unspecified,Gender,,,Palestine,,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health information systems,2020 +P23313,109476,Community approaches for improved health outcomes of urban refugees in Lebanon during the COVID-19 pandemic,"This project will strengthen Lebanon'Äôs public health response to COVID-19 and future health emergencies in fragile settings. It will use a multi-pronged approach to meet the needs of refugees and share knowledge to benefit similar needs in Jordan. First, there will be a critical assessment and analysis of the rapid-response actions and policies that have guided Lebanon'Äôs management of the pandemic at the national level. This will be complemented by interventions to manage and mitigate risks posed by COVID-19 at the community level. The project will also build capacity for pandemic responses at the local and regional levels. Experiences at the local, national, and global levels will be triangulated to identify good practices and recommend changes. The project will produce guidance to inform a robust national public health response system that benefits both refugee and host communities and that is gender-responsive and inclusive of diverse populations.",,,American University of Beirut,967469,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Unspecified,Gender,,,Lebanon,,"Policies for public health, disease control & community resilience",Community engagement | Policy research and interventions,2020 +P23314,109477,Managing impact of COVID-19 in Rohingya refugee camps with culturally appropriate technological solutions,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leveraging existing local opportunities to strengthen the overall initiative. This project will identify gaps in COVID-19 responses in addressing sexual and reproductive health and maternal and neonatal child health issues among Rohingya refugees and host population women and adolescent girls in Bangladesh. Bangladesh hosts the largest refugee camps in the world, with close to 860,000 stateless Rohingya refugees. The project will use qualitative and quantitative approaches to examine potential health impacts of COVID-19. It will also assess whether deployment of digital interventions (a contact tracing application and a maternal and neonatal child health application) can reduce transmission of COVID-19 and improve sexual and reproductive health and maternal and neonatal child health outcomes respectively. The project will engage government and other key stakeholders to develop and build evidence on the use of these tools. The evidence will inform local policies and the health systems set up in the refugee camps and host communities to combat COVID-19. It will also inform any future health emergencies, enhancing the preparedness and early response aspects of the health system.",,2023,The BRAC University,536623,Human Populations,Asian,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,South-East Asia,Unspecified,,,,Bangladesh,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2020 +P23315,109478,Effectiveness and scalability of innovative digital health solutions responding to COVID-19 crisis among refugees and vulnerable populations,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations, and leveraging existing local opportunities to strengthen the overall initiative. This project will investigate the effectiveness of developing and scaling up three digital health solutions in strengthening health systems and improving access to care in at-risk populations in Asia, the Middle East, and Africa. The two-year project will use the current COVID-19 pandemic to identify existing gaps in preparedness and early response of health systems. The approach will include quantitative and qualitative methods to study three critical areas related to health emergencies: early detection of illness in at-risk populations; teleconsultation to improve access to care for the hard-to-reach; and mobile applications for best practice guidelines for healthcare workers. The evidence will be communicated through a variety of academic and policy outputs.",,2023,Aga Khan Foundation Canada/Fondation Aga Khan Canada,477420,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Health Systems Research,Health service delivery | Health information systems,2020 +P23316,109479,"Exploring and learning from evidence, policy, and systems responses to COVID-19 in West and Central Africa","An effective response to COVID-19 requires a complex array of relevant evidence packaged in user-friendly forms to support decision-making about current and future responses. This project will map out existing evidence and its use in informing responses to COVID-19. It will identify sectoral evidence gaps (epidemiological, public health, health system, and health technology capacities, etc.), as well as intervention responses to emerging epidemics and pandemics. It will document, compare, and contrast experiences at national and subnational levels, with a focus on displaced and vulnerable populations across countries and sub-regional contexts. The project will be implemented in six countries in West and Central Africa: Benin, the Democratic Republic of Congo, Ghana, Guinea, Nigeria, and Senegal. To cope with the fast-moving nature of the COVID-19 pandemic, the team is adopting a flexible study approach with iterative analysis over time. The deeper understanding generated by the project will support more detailed work and interventions that benefit displaced and other vulnerable populations. It will have an emphasis on integrating equity and gender considerations, with attention to information and experiences affecting vulnerable populations. The research team will engage with decision-makers to inform evolving decision-making and serve as a strong basis for building resilient health systems. The work will contribute to identifying areas for inclusion in sub-regional observatories and follow-up work in the West and Central Africa region for improved evidence-informed decision-making. The project will build collaborative learning within and across countries through discussions and policy dialogues with key stakeholders to inform appropriate multisectoral responses to COVID-19 and similar health emergencies.",,2023,Ghana Health Service,937050,Unspecified,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Ghana,,"Policies for public health, disease control & community resilience | Health Systems Research | Research on Capacity Strengthening",Approaches to public health interventions | Policy research and interventions | Systemic/environmental components of capacity strengthening,2020 +P23317,109480,Strengthening access to sexual and reproductive health services for internally displaced people during COVID-19 in Burkina Faso,"Refugee and displaced populations, and the vulnerable communities with whom they share space, are at high risk for acquiring COVID-19 because their living conditions make it impossible to practice physical distancing and isolation or to access quality healthcare. Refugee women are particularly vulnerable because their limited access to sexual and reproductive health services and products is further interrupted and their duties as caretakers, especially in under-resourced refugee settings, are increased. This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis in the short-term and the longer term. The initiative will support research on resilience building and preparedness to serve the needs of refugees and other populations on the move by promoting inter-sectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations. It will also leverage existing local opportunities to strengthen the overall initiative. This project will assess and respond to the needs of an internally displaced population in the fragile context of Burkina Faso, where growing conflict and terrorism may turn into a chronic development crisis. It focuses on increasing access to sexual and reproductive health services and related rights of internally displaced adolescents and women in the context of COVID-19. Firstly, it will identify the needs, constraints, and facilitating factors for using such services before developing and implementing an intervention to improve access to and awareness of sexual and reproductive health services and rights. The project will document the results and disseminate them as lessons learned to strengthen current and future responses to similar health crises.",,,Université Joseph KI-ZERBO,430680,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Burkina Faso,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P23318,109481,"Improving the health and empowerment of migrants, women, and children in Guatemala during the COVID-19 pandemic","This project will study the effects of COVID-19 on the health of refugees and Indigenous populations in parts of rural Guatemala that are experiencing recent waves of refugees migrating into Indigenous communities. This project builds on the existing Network of Community Health Defenders, which monitors healthcare services and policies, and will expand the Network from 30 to 35 rural Indigenous municipalities in Guatemala. In recent years, the Defenders have reported that migrants deported from Mexico or the USA are choosing to stay and live in the Indigenous communities rather than returning to their countries of origin. This is leading to tensions and hostilities within already economically vulnerable communities, and now the COVID-19 pandemic is exacerbating vulnerabilities of women and their families in host communities, as well as among refugees and migrants. To inform the rapid response component of this project, the Defenders will assess health needs, perceptions of COVID-19 risk of infection, and related fears of refugees, migrants, women, and children, and the barriers they experience to access available public services. Based on the findings, and through a community participation approach, the researchers will design policy engagement strategies and specific programs for these vulnerable populations. The strategies and programs will emphasize the empowerment of women. For longer-term preparedness, the project will also analyze how national and social media and other cultural factors are contributing to narratives that maintain and exacerbate gender inequalities, increase fear of the health system among women and other vulnerable populations, and increase social rejection and subsequent health risks of migrants. The project will test positive communication strategies and messages to reduce the fear of COVID-19 among refugees, migrants, women, and communities, support gender equality, and build trust between users of services and healthcare providers 'Äî key elements in pandemic preparedness and resilience.",,2023,Centro de Estudios para la Equidad y Gobernanza en los Sistemas de Salud (CEGSS),406408,Human Populations,Other,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Internally Displaced and Migrants | Indigenous People | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Guatemala,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P23319,109484,Generating knowledge and building networks for science advice in emergencies,"The COVID-19 pandemic, like climate change and other major threats, is pervasive worldwide. This recognition is at the core of the UN'Äôs 2030 Agenda and embedded within each of the Sustainable Development Goals (SDGs). Yet a clear understanding of our shared threats and the means to mitigate them is less well developed. This is in part because the required structures for government science advice are often weak or absent, particularly in the Global South. Since 2014, the International Network for Government Science Advice (INGSA) has been at the vanguard of global efforts to instil evidence-based policymaking by drawing on national science systems as a major part of efforts to advance the SDGs. These efforts included a three-year IDRC-funded initiative from 2017 to support research, training, and networking in the Global South, under the auspices of the International Science Council. In 2020, INGSA'Äôs work has taken a new and urgent turn in the context of the COVID-19 global pandemic, acting as a conduit between national public health agencies and research organizations and establishing a platform of information sharing and data collection about how related policy decisions are being made. This project will build on INGSA'Äôs earlier work involving the Global South and on its initial efforts in response to the COVID-19 pandemic. It will focus on ideas, institutions, individuals, and modes of integration that can greatly enhance how science advice occurs in Asia, Latin America, and Africa, with an emphasis on responses to the pandemic and to emergencies more generally. It will support a comprehensive comparative study of COVID-19 responses through original research, including the creation of a new global platform for tracking related policies as well as 'Äúdeep-dive'Äù case studies. This will help governments better prepare for transnational crises by using high-quality scientific evidence. In parallel, the project will pilot a regional network of high-level science advisors linked to a policy intelligence platform for Southeast Asia and explore scaling out possibilities for other regions. Finally, it will rely on INGSA'Äôs three regional chapters in Asia, Latin America, and Africa to generate new knowledge and regional insights, promote science advice to policymakers, and integrate information across regions, with an early emphasis on COVID-19.",,2023,Conseil international pour la science / International Science Council,551744,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,France,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P23320,109485,Rectifying the effects of COVID-19 on vulnerable populations in West Africa: a research-action (RECOVER),"The full impact of COVID-19 on West Africa'Äôs vulnerable populations is not well understood. Beyond the effects on immediate health status, rising rates of sexual and gender-based violence and teenage pregnancy point to a significant negative impact as a direct consequence of the pandemic. Uncoordinated responses may unintentionally worsen these and other effects. This project supports the development of innovative strategies that will overcome this patchy knowledge of COVID-19'Äôs impact and address the fragmentation in policy responses to directly and coherently address the priority needs of vulnerable communities. Initially, researchers will undertake a rapid assessment of both the preliminary effects of COVID-19 and policy responses and strategies across the region to inform immediate, short-term policy and programmatic responses. The second stage will develop detailed case studies to expose specific COVID-19 impacts on vulnerable populations and a responsive policy framework and multisectoral approach to address these impacts for the post-COVID-19 era. Applying action-research methodologies, the project will collaborate with communities, policymakers, and implementers to jointly analyze the results and develop responses. This project aims to support West African countries to prepare for future pandemic outbreaks and minimize impact on vulnerable populations. It will strengthen collaboration and learning across seven Francophone and Anglophone research institutions and allow West Africans to develop relevant solutions to address their own specific regional challenges related to pandemics in both the short- and long-term.",,,Ghana Health Service,801600,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Ghana,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Policy research and interventions | Indirect health impacts | Social impacts | Economic impacts,2020 +P23321,109486,Informal workers and COVID-19: evidence-based responses to the crisis at the base of the economic pyramid,"This project focuses on the impact of the COVID-19 pandemic and associated lockdowns on the livelihoods and health of poor workers, especially women, in the informal economy. Over 90% of workers in developing countries are informally employed, with higher rates of informal employment for women. While the impact of the pandemic has been catastrophic for these workers, evidence on how they are affected is not yet available to inform a policy response, especially during the recovery phase. The informal economy is so diverse that nuanced information is required about how the crisis exacerbates existing vulnerabilities for different groups of informal workers and about how different groups of informal workers contribute as essential frontline workers. This project will do so using a mixed-methods longitudinal study that includes a large-scale survey of informal workers spanning over 10 cities across eight countries, with a focus on four groups that predominantly employ women: domestic workers, home-based workers, street vendors, and waste pickers. The findings will inform policies and actions needed to address the impacts of the pandemic. They will also highlight how existing responses are affecting informal workers in ways that deepen or reduce inequalities. Ultimately, this project will contribute novel and contextually grounded evidence to ensure a fundamental rethink of the underlying injustices and inequities that exacerbate the negative impact of the pandemic on informal workers, with a focus on women.",,2022,Women in Informal Employment: Globalizing and Organizing (WIEGO) Limited,687295,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P23322,109487,"Economies beyond emergencies: assessing impacts of COVID-19 policy responses on informal workers in India, Kenya, and Uganda","The COVID-19 pandemic has wrought a global socio-economic crisis, with profound implications for the wellbeing of individuals, households, and communities. It has further deepened existing social inequalities and heightened risks for gender-based violence and violation of sexual and reproductive health and rights among marginalized groups. The disruption in livelihoods and protective networks has undermined the bargaining power of women, exposing them to higher risk of abuse and exploitation in domestic and public spaces and in the workplace. This further sets the stage for the increased occurrence of harmful traditional practices that are anchored in gender norms, such as female genital mutilation, early and forced child marriages, and child labour. This project will undertake research to inform gender-responsive, accountable, and democratic policies and strategies that ensure vulnerable populations affected by COVID-19, such as female workers in informal urban economies, can recover and rebuild their lives and livelihoods. Research in three urban settings in India, Kenya, and Uganda will generate data on the impact of the COVID-19 response on women workers in the informal economy. This will provide an understanding of how gender norms, pathways to economic empowerment, and the gendered impacts of violence and access to essential health services can inform policy that is responsive to the specific needs of women workers in these informal economies.",,,Asylum Access,664231.5,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Sexual and gender minorities,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts | Other secondary impacts,2020 +P23323,109489,"Socio-economic impact of COVID-19 on African economies, social cohesion, and governance: evidence from Benin, Burkina Faso, and South Africa","This collaborative project will contribute to policies and strategies to address the immediate and longer-term effects of the COVID-19 pandemic on economies, social cohesion, and governance in Benin, Burkina Faso, and South Africa. The multidisciplinary and multi-country team of researchers, composed of both men and women, will investigate the negative income shock and state regulations resulting from the pandemic and their corresponding effects on social cohesion, governance, and violence (including violent extremism) in Africa. They will employ mixed methods and a comparative approach across contexts, conduct experiments, and analyze secondary data sources, incorporating a strong gender analysis throughout. The study findings will be positioned for use by policymakers, practitioners, and civil society actors to inform the design and implementation of effective responses to the various effects of the COVID-19 pandemic in Benin, Burkina Faso, South Africa and beyond. The project will contribute to enhancing collaboration between researchers in Africa and strengthen their contribution to the development of effective and rapid responses to the social and economic effects of the pandemic in Africa.",,,African School of Economics,884760,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Benin,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P23324,109490,Strengthening public policies for decent work in Francophone Africa in the context of the COVID-19 pandemic,"The project seeks to analyze the impact of the COVID-19 pandemic on small informal businesses in Benin, Cameroon, Morocco, and Senegal. It will explore policy options for targeted support to those businesses in a way that helps contain the spread of COVID-19 and similar pandemics in the future. It will also seek to identify the best options for building the long-term resilience of vulnerable population groups involved in small informal businesses. Using mixed methodologies, the research team will conduct multidisciplinary analyses integrating gender considerations to better understand the specific challenges facing women and young people. It will then propose appropriate strategies for tailored support. The findings will help to inform the deliberations of the presidential COVID-19 response unit in Senegal, the bureau for economic analysis at the Presidency of Benin, and the COVID-19 national response unit in Cameroon.",,2023,Université Cheikh Anta Diop,902572,Human Populations,Black,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Senegal,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P23325,109491,Promoting resilience in COVID-19 MENA: building inclusive and effective social protection and safety nets,"This project is part of an initiative that will provide evidence and strengthen capacity for bridging the knowledge gap in responding to the growing COVID-19 health crisis both in the short term and in the longer term. The initiative will support research on building resilience and preparedness to serve the needs of refugees and other populations on the move by promoting intersectoral approaches, including building bridges between humanitarian and development responses to reduce and control health risks for displaced populations. It will leverage existing local opportunities to strengthen the overall initiative. This project will generate evidence on the effects of the COVID-19 pandemic on refugees and internally displaced people in the West Bank and the health system'Äôs ability to meet their needs. It will also strengthen the health system through incorporating research and health information system improvements. Activities will include initial rapid situation assessments and community engagement to analyze the pandemic response and engage with institutional and policy stakeholders. This will be followed by larger scale quantitative and qualitative research activities. Finally, the research will be presented in an accessible format for policymakers and practitioners to inform long-term health system preparedness and resilience. The project will also support capacity building for research in health system preparedness with regards to human resources, information systems, and community engagement. This will lead to enhanced knowledge production, both for short-term rapid response to COVID-19, and for a long-term participatory approach to pandemic preparedness and resilience from a gender and equity perspective for refugee and internally displaced populations.",,2022,"ARI, Centre pour une initiative de réforme (ARI)",1094416,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,Gender,,,France,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +P23326,109492,The impact of COVID-19 on inclusive development and democratic governance: rapid and post-pandemic assessment in the Mekong subregion,"This project aims to support inclusive, coordinated, and gender-sensitive responses to the COVID-19 pandemic in Cambodia, Laos, Myanmar, and Vietnam. It will assess the socioeconomic impacts of the COVID-19 pandemic and the effectiveness of responses. The project will explore the current conditions of the economy, firms, and workers, the policy responses intended to support them, the mitigation strategies they have employed, and the level of coordination across various actors that is critical to a strong and inclusive recovery. In close coordination with local governments and organizations, the project will identify gender-sensitive policies and good practices from the macro to micro level that will support the recovery process and improve resilience among vulnerable women workers and micro, small, and medium enterprises. It will facilitate policy dialogue and coordination among researchers, policymakers, private sector actors, civil society, and women'Äôs organizations in the response and recovery phases. Finally, it will enhance the capacity of the implementing consortium members to create partnerships, cooperation, and learning at the regional level with international dialogues, comparative research activities, and by engaging regional organizations.",,,The Cambodia Development Resource Institute,1070545,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,Unspecified,Gender,,,Cambodia,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P23328,109494,Impact of COVID-19 on family farming and food security in Latin America: evidence-based public policy responses,"The COVID-19 pandemic is threatening the livelihoods and food security of millions of people. Family farming provides a significant share of the food supply and has an important role in the transition toward sustainable agri-food systems and the fight against a possible food crisis. This sector is facing multiple challenges that are exacerbated under the current pandemic. This project, implemented in Chile, Colombia, Ecuador, Guatemala, and Mexico, will generate evidence and promote changes to agri-food systems in the aftermath of the pandemic. It will contribute to mitigating the impact on food security and consumption patterns of the most vulnerable, with an emphasis on women. It will promote small- and medium-scale farming, in addition to agri-food systems that are more sustainable, gender-sensitive, inclusive, and resilient to shocks such as the COVID-19 pandemic.",,2023,"[Corporación de Derecho Privado ""Rimisp"" - Centro Latinoamericano para el Desarrollo Rural] or [Corporación Rimisp]",1027638,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,,,,,Chile,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23329,109495,"Addressing the socioeconomic impacts of COVID-19 with a gender lens: food systems, labour markets, and social protection in Latin America","The COVID-19 pandemic and confinement are causing severe disruption to labour markets and food security in Latin America, exacerbating structural labour market challenges such as informality, inequality, and low productivity. Millions of workers are left unprotected, highlighting the need to strengthen social protection systems. The impact on the food system is exacerbating inefficiencies and inequalities, putting the livelihoods of small producers and access to healthy food for poor consumers at risk. So far, most Latin American governments have failed to enact policy measures to tackle these problems. This project will support evidence, technical assistance, and a pilot of policy responses addressing food systems, labour market challenges, and social protection that emphasize gender and diversity. It will propose timely and cost-effective policy responses to foster food security and more efficient and inclusive traditional food markets; support the design and piloting of innovative social protection programs to reach informal workers; and inform temporary employment policies for Latin America to reduce the socio-economic impacts of the pandemic and to promote a more equitable and sustainable recovery. The project will also have global reach and foster Southern researchers'Äô visibility and leadership, with at least 15 scholars from the region engaging on global policy dialogues on COVID-19 responses. The project will be implemented in Peru, Ecuador, and two additional Latin American countries that will be selected according to the impact of the pandemic, potential for policy impact, and research capacities.",,,Group of Analysis for Development / Groupe d'analyse pour le développement / Grupo de Análisis para el Desarrollo,1096458,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Peru,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts | Other secondary impacts,2020 +P23330,109496,"Shaping the macro-economy in response to COVID-19: a responsible economic stimulus, a stable financial sector, and a revival in exports","This project aims to contribute to the knowledge on macroeconomic policies that are key for responses to the COVID-19 pandemic in low-income countries. The impacts of the pandemic on the economies of these countries is significant, contributing to growing poverty and hunger. There is an urgent need for credible data, analysis, and advice for the economic policies and the fiscal and monetary measures required to mitigate the impacts and promote an inclusive and sustainable recovery. The project will be led by the Overseas Development Institute in the UK, in collaboration with think tanks in Bangladesh, Sri Lanka, Kenya, Tanzania, and Peru, and the network Southern Voice. This partnership will develop credible evidence that can support national and international policies in response to the pandemic, focusing on macroeconomic performance, growth scenarios, and macroeconomic policy options, with a focus on gender equality and climate change outcomes.",,2022,ODI,345876,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2020 +P23331,109497,Addressing COVID-19-related vulnerabilities for migrant returnees in Central America'Äôs Northern Triangle,"Central America'Äôs Northern Triangle (Guatemala, Honduras, and El Salvador) is well known for its high rates of violence and poverty, correlated with high rates of migration under vulnerable conditions. Recent shifts in migration policy, particularly in the USA, have contributed to a mass return of Central Americans. The COVID-19 crisis has further aggravated the invisibility and vulnerability of these returnees (particularly youth and women) and has exposed their dire economic and security conditions amidst the pandemic. These include growing rates of gender-based violence, difficulties accessing economic opportunities, and poor access to basic services and information, both in quarantine centres and upon their reintegration into host communities. This project seeks to promote efficient policy responses by identifying and addressing the labour reintegration and gender-based violence challenges and experiences faced by migrant returnees in the Northern Triangle with an emphasis on female and youth returnees. It will also examine the different vulnerabilities that COVID-19 imposes in these contexts. A diagnosis of returnees'Äô economic and security vulnerabilities will be conducted in six communities across the Northern Triangle, involving surveys and interviews with migrants, local organizations, and public officials. It will evaluate the most effective short and medium-term responses required to meet the economic and human security needs of these returnees. Engagement efforts to promote uptake will include discussion forums and information campaigns.",,,Asociación de Investigación y Estudios Sociales/Association for Research and Social Studies,925000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Guatemala,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P23332,109498,Providing timely evidence to facilitate socio-economic recovery from the COVID-19 pandemic in Rwanda,"This project aims to facilitate evidence-based decision-making to provide appropriate socio-economic responses to the COVID-19 outbreak in Rwanda. Over a period of three years, the project will collect data on a set of 10,000 vulnerable households and 4,500 micro-, small-, and medium-sized businesses. The goal is to gather instantaneous and ready-to-use information on the socio-economic and labour market impacts of COVID-19. The information will be disseminated to decision-makers and other stakeholders and will provide the basis for the development of policy options for the Government of Rwanda to respond to challenges faced by businesses and households. The project will also reinforce the capacities of researchers in Rwanda.",,2023,Institute of Policy Analysis and Research (IPAR-Rwanda),744089,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Rwanda,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2020 +P23333,109499,"Supporting small and medium enterprises, food security, and evolving social protection mechanisms to deal with COVID-19 in Pakistan","To prevent the spread of COVID-19 infections, Pakistan enforced a strict lockdown and quarantine system. This system, however, is negatively affecting many sectors of the economy, with a disproportionately high impact on the livelihoods of the most vulnerable. Among the most affected sectors are food production and disrupted food supply chains, where small and medium enterprises are facing massive layoffs or closures. This project will provide evidence-based advice to the government of Pakistan to respond to the crisis, guide rapid policy responses, and develop measures to build resilience for the post-COVID period. It will generate and feed information to a national food security dashboard to facilitate the transportation of food commodities from surplus districts to deficit districts, contributing to food security. The project will also map formal and informal small and medium enterprises (SMEs) in the country and provide evidence on the effectiveness of the current stimulus package to strengthen national SME policy. In addition, given that existing social safety nets are insufficient to support the 60% of Pakistan'Äôs labour force working in informal undocumented sectors of the economy, there is an urgent need for an in-depth analysis of existing social protection mechanisms to devise a roadmap for a universal social protection regime in Pakistan. The project will help fill information and action gaps and serve as a bridge between policymakers and the needs of millions of daily wage earners in rural and urban areas, leading to positive impacts on the livelihoods of millions of vulnerable Pakistanis.",,2023,Sustainable Development Policy Institute,525030,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Vulnerable populations unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,South-East Asia,Unspecified,,,,Pakistan,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P23334,109500,"Social engagement, citizen agency, and governance: toward a new democratic consensus in post-pandemic Latin America","This project seeks to understand how governments and citizen groups have organized responses to the COVID-19 crisis, and the social, political, and institutional dynamics that shaped responses in Argentina, Bolivia, Chile, Colombia, Guatemala, and Mexico. It will assess how the pandemic and the responses to the crisis have affected the social contract between citizens and the state as well as the social cohesion among citizens. The project places a special emphasis on how the pandemic has affected the ability of women and vulnerable populations to shape strategies in the context of the already high poverty rates of women, Indigenous people, and those of African descent. The groups most vulnerable to the economic and health impacts of COVID-19 are also the most likely to be politically marginalized during the crisis. The project'Äôs aim is to support improvements in the policies and practices of engagement with vulnerable groups for both civil society organizations and government agencies. It will identify both failings and innovations in governance by examining practices of citizen engagement, distinct political arrangements, approaches to policy co-creation, and the use of technology as a tool for connecting state agencies and policymakers to the public. It will highlight models of leadership and governance in response to the crisis. It aims to strengthen civil society-led initiatives, incorporate new innovations, and help mobilize the agency of vulnerable groups. Finally, the activities will inform discussions about how to revitalize democratic politics amid declining public trust in traditional political institutions.",,,Universidad ICEducation and ScienceI,977324,Human Populations,Black,Unspecified,Unspecified,Indigenous People | Sexual and gender minorities | Other,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Colombia,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Policy research and interventions,2020 +P23336,109507,Technical and communication support to achieve and scale the impact of the COVID-19 Global South AI and Data Innovation Program,"The COVID-19 crisis has been called a data-driven pandemic, with massive amounts of data being generated, collected, shared, and analyzed, and provided for public consumption. There are lessons from epidemics such as SARS-COV-1, H1N1, Zika, and Ebola that point to the need for reliable and timely data. Early steps were taken in these prior epidemics to leverage data from novel sources, including the private sector. In the current context, many data-enabled innovations have been developed to facilitate early detection, contact tracing, quarantine monitoring, and timely interactive public communication. Data-enabled innovations are being used to inform policy relating to isolation and economic lockdowns. While data is crucial, it is important to ensure appropriate safeguards when dealing with personal data originating either directly from citizens or through the private sector. For example, though there is great value in leveraging personal data held by mobile operators for tracking movement, the Global System for Mobile Communications (the mobile industry association), updated its privacy guidelines for the use of mobile network big data in the context of COVID-19 to protect communication rights. This project aims to enable multidisciplinary research to deepen our understanding of how to develop and scale responsible (inclusive, rights-based, ethical, and sustainable), evidence-based artificial intelligence and data science approaches that support response and recovery to COVID-19 in low- and middle-income countries. A technical resource hub will facilitate synergies between projects of the COVID-AI program, synthesize research findings, and facilitate engagement between the COVID-AI program and national and regional policymakers.",,2023,United Nations Development Programme/Programme des Nations Unies pour le développement/Programa de las Naciones Unidas para el Desarrollo,401325,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P23337,109518,Strengthening inclusive open data systems in Africa and Southeast Asia,"In Africa and Asia, open data is increasingly regarded as an important tool to address complex development challenges. For example, the urgency and scale of the COVID-19 crisis has led some governments to open and share relevant data to enable evidence-based policy, support accurate reporting around the crisis, and inform inclusive social and economic recovery measures. However, there are still many challenges to realizing the benefits of a data-driven approach, including the need to build capacity among key stakeholders, support effective policies and practices, and learn from data innovations. There is a need to specifically address the lack of inclusive, disaggregated data on issues meaningful to women. This project will explore data infrastructure, governance, and use issues, building on the past research and action from the Open Data for Development Network. In Africa, specific focus will be on building capacity and model policies with governments, availability of data in Africa, and the potential to explore innovative uses, like fighting against corruption. The project will also examine data innovation at the intersections of gender, education, food security, and climate change, with a focus on action to address the challenges brought by COVID-19 and the African locust swarm. Finally, it will explore the role that increased transparency of political party data might play in women'Äôs political party leadership. In Asia, the project will explore how collaborative approaches to technology development and machine learning can improve parliamentary transparency and access. The project will explore indigenous data sovereignty and management as well as working with women in local communities to use open data to defend their rights to water access and food sovereignty. The project will also support capacity building and data use for governments and civil society stakeholders and contribute to policy approaches to increase transparency and responsible release of high-quality data. This project builds on the Open Data for Development (OD4D) program, a global network that uses data to promote social good. OD4D is supported by IDRC, Global Affairs Canada, and The William and Flora Hewlett Foundation.",,2022,Local Development Research Institute,448430.24,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Data Management and Data Sharing,,,Kenya,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23338,109527,Simulations and field experiments of policy responses and interventions to promote inclusive adaptation to and recovery from the COVID-19 crisis,"This project aims to assess the impacts of the COVID-19 pandemic on national economies and determine the effectiveness of current and potential policy responses in 11 developing countries around the world. It will analyze factors such as sectoral/total production, employment, trade, etc. on national economies, and particularly on household poverty/inequality. It will simulate the impacts of socio-economic policy responses during the lockdown, reopening, and recovery phases and develop a policy simulation model that local researchers and government officials may use to address other policy challenges during and after the current project, and to support governments in the design of effective policy responses. It will also identify general lessons to guide policies in other developing countries.",,2023,"Partnership For Economic Policy, Inc.",878044,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Kenya,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P23339,109528,The impact of the COVID-19 pandemic on livelihoods in Africa,"This project will undertake research on the impacts of the COVID-19 pandemic on the livelihoods of vulnerable populations in Ethiopia, Kenya, Nigeria, Senegal, South Africa, and Zambia. The goal is to inform evidence-based decision-making in the policy responses to the COVID-19 pandemic in these countries. The project will evaluate the impact of the pandemic on key macroeconomic indicators and on issues such as food security, malnutrition, and hunger. It will also examine gender-specific socio-economic impacts. The project aims to build the capacity of researchers and institutions for longer-term, sustainable policy changes that address root causes of the pandemic'Äôs unequal impact, including gender inequality. It also aims to build a network of stakeholders (individuals and policy, research, and practice institutions) that can continue to track the pandemic'Äôs impacts and design and advocate for practical solutions in the post-COVID era.",,,African Economic Research Consortium/Consortium pour la recherche économique en Afrique,893958,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Kenya,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +P23340,109529,Mitigating socio-economic impacts of COVID-19 and promoting post-pandemic resilience in Uganda,"This project will examine the policies, measures, and strategies to mitigate the socio-economic impacts of COVID-19 on households and small and medium-sized enterprises. It will also look at the interventions required to re-activate resilience of the Ugandan economy post-COVID-19. Using quantitative and qualitative methods, it will examine how the pandemic has affected business operations, the coping mechanisms businesses have adopted, and the support they require. The study will generate country-specific data and evidence-based research on the immediate, short-, medium-, and long-term impacts of the pandemic, mitigation measures, and policy responses. The findings will feed directly into ongoing policy processes to find solutions to the problems caused by the pandemic in Uganda.",,,Economic Policy Research Centre,486675,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Uganda,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P23342,109531,"COVID-19 and the youth question in Africa: impact, response, and protection measures in the IGAD region (COYOQA)","This project will not only analyze how young people are affected by COVID-19, it will examine how they can be key actors in the response, mitigation, and evaluation efforts of pandemic policies and actions. It aims to ensure that emerging policies are responsive and promote inclusive governance and accountability by seeking to investigate how social accountability can be factored into COVID-19 responses in three member states (Ethiopia, Kenya, and Uganda) of the Intergovernmental Authority on Development (IGAD), a regional bloc of eight member states in the Horn of Africa. The project focuses on enabling youth-driven documentation of reliable, contextually grounded local data analysis and rapid feedback to local and national authorities and to communities through the development of a citizen-led performance monitoring framework. The focus is on informing policies and decision-making to mitigate the social and economic impacts of COVID-19 and prevent its re-emergence. This project will support youth-led policy influence and encourage the use of research evidence to improve community responses to impacts of COVID-19 and build resilience. By providing rapid support to ongoing work, innovating new ways of learning and sharing, and enhancing capacities to inform current and future policy and practice solutions, the project aims to strengthen the overall governance of the COVID-19 crisis and its aftermath. Ultimately, the project seeks to contribute towards strengthening the social contract and fostering democratic peace in pandemic and post-crisis responses.",,2023,Organization for Social Science Research in Eastern Africa and Southern Africa,761625,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Ethiopia,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Social impacts | Economic impacts | Other secondary impacts | Health leadership and governance,2020 +P23343,109532,COVID-19 macroeconomic policy response in Africa,"Many developing countries do not have sufficient financial, monetary, and social instruments for the necessary immediate and long-term responses to the COVID-19 pandemic. This project aims to inform policy responses in Benin, Nigeria, Senegal, South Africa, Tanzania, and Uganda. It will generate evidence to support policymakers, specifically finance ministries, to promote equitable socioeconomic and sustainable environmental policies and interventions in the short and long- term. The project will also support peer learning and capacity building among targeted policymakers and policy think tanks for strong pandemic responses on fiscal and monetary measures, financing and programming options to support vulnerable groups, and rebuilding economies to be climate-resilient, sustainable, and inclusive.",,,The South African Institute of International Affairs,1085583,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,South Africa,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P23344,109547,"Portable, low-cost hardware for decentralized COVID-19 diagnostics for Canada, Colombia, and Ecuador","The unfolding COVID-19 pandemic highlights the critical need for a diverse diagnostics strategy. Reliance on a single, highly centralized diagnostic technology, such as polymerase chain reaction (PCR), has led to supply chain disruption and bottlenecks in testing access. As attention is turning to the tools needed to relaunch economies, two capabilities have been identified as key: decentralized diagnostic testing for COVID-19 and serological testing to screen population antibody levels. This project aims to develop, validate, and implement the molecular tools and hardware required to support the decentralized, high-capacity diagnostic and serological testing to respond to the COVID-19 pandemic in Canada, Colombia, and Ecuador. The team proposes adapting a previously designed portable plate reader to deploy two key diagnostic modalities: a rapid (15 minute) molecular COVID-19 virologic test and serological testing of antibodies. Implementation and testing of this decentralized diagnostic capacity will be performed at small businesses in Canada, and with hospital workers and remote populations in Colombia and Ecuador. Together these tests will prevent a resurgence of infections as communities begin to reduce lockdown restrictions. It will also determine the prevalence of antibody levels in the population, which may help to promote strategic use of future vaccine stocks. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2022,The Governing Council of the University of Toronto,323043.98,Other,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2020 +P23345,109548,Broad-spectrum antiviral nasal sprays to prevent infection by SARS-CoV2 and seasonal respiratory viruses in patients and healthcare providers,"In March 2020, the World Health Organization declared a pandemic due to the emergence of a novel coronavirus (SARS-CoV2) which causes COVID-19, a potentially lethal respiratory infection. There are currently no antiviral agents to prevent or treat SARS-CoV2 infections. This project proposes the optimization and prototype development of a broad spectrum antiviral pharmaceutical preparation (RespVirex) to protect healthcare workers and high-risk patients from SARS-CoV2 and dozens of other seasonal and pandemic viruses. The team aims to deliver RespVirex by nasal spray and nebulized aerosol. A nasal spray can be dosed conveniently by healthcare workers as needed during respiratory virus seasons or a pandemic. RespVirex can also be inhaled by nebulizer to treat the lower respiratory tract. The pharmaceutical formulation of the nasal spray and nebulized aerosol will be developed in Canada, while its ability to inhibit SARS-CoV2 and other respiratory viruses will be evaluated at the Institut Pasteur in Dakar, Senegal. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2021,The Governors of The University of Alberta,490235.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P23346,109549,Kukaa Salama (Staying Safe): COVID-19 prevention practices with urban refugee and displaced adolescents in Uganda,"This project will respond to the need for COVID-19 prevention among urban refugee youth who experience poverty, overcrowded living conditions, and poor sanitation that increase COVID-19 risks while limiting their ability to practice mitigation strategies such as frequent hand washing and physical distancing. It directly addresses social, policy, and public health responses and related indirect consequences among the priority population of refugees in countries with weaker health systems. The project will develop and evaluate an mHealth (mobile) intervention with urban refugee youth and adolescents aged 16-24 in low-income contexts in Uganda. The goals are to increase population-level containment strategies (physical distancing, hand and respiratory hygiene); use tailored public health communication that accounts for gender, culture, context, and language; and emphasize citizen engagement with active, intentional dialogue between refugee youth, the Ministry of Health, academics, and refugee agencies. The study comprises three phases: qualitative research to explore factors associated with uptake of COVID-19 mitigation practices; developing, implementing, and testing the Kukaa Salama intervention that integrates qualitative findings into behavioural change techniques; and knowledge mobilization, including a COVID-19 refugee policy analysis. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2022,The Governing Council of the University of Toronto,215529.58,Human Populations,Black,Adolescent (13 years to 17 years) | Adults (18 and older),Urban Population/Setting,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication,2020 +P23347,109550,Household transmission of SARS-CoV-2 in a well-characterized Kenyan cohort,"Although critically important for determining optimal strategies to reduce transmission and limit the impact of SARS-CoV-2 (COVID-19), factors such as the frequency of household transmission, the proportion of asymptomatic infection, and the natural history of the infection are poorly understood. These knowledge gaps are even greater in low-resource countries, such as Kenya, where population age, household size, living conditions, nutrition, prior infections, and other factors may have significant effects on social policies and public health interventions. This project will address these gaps and provide evidence to inform decisions by undertaking a household transmission study in an African community to examine the determinants of transmission, including the role of children and the viral load of exposures. It will provide several pieces of relevant information for COVID-19 vaccine development efforts. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2022,The University of British Columbia,328963.55,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease transmission dynamics,2020 +P23348,109551,Assessing the impact of COVID-19 response on malaria control and malaria burden,"The rapid global emergence and spread of COVID-19 is having extensive effects on the health of populations and health systems worldwide and is threatening fragile health systems in many resource-poor countries. When responding to the COVID-19 pandemic, it is critical to ensure that efforts to control other endemic diseases, such as malaria, are not ignored. Between 2000 and 2015, the massive scale-up of malaria vector control interventions, including long-lasting insecticidal nets, and effective treatment of clinical malaria cases, led to a 50% reduction in malaria cases and deaths in sub-Saharan Africa. There are concerns that tackling COVID-19 will disrupt malaria control efforts, leading to a resurgence in malaria and undermining progress to date. This project investigates the social and public health response to COVID-19 in Tanzania and assesses the impacts of the pandemic on malaria prevention and control at the community and health system levels. The team will identify gaps in the delivery and uptake of malaria interventions in the context of COVID-19. Real-time data on individual behaviours and the effects on health systems will inform locally adapted malaria control strategies. This project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and other funders.",,2022,University of Ottawa/Université d'Ottawa,99004.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P23349,109552,Protecting Healthcare workers from COVID-19,"While there is general agreement on many aspects of policy to protect healthcare workers, approaches to implementation have varied widely in response to local circumstances and there is limited evidence available to guide local decisions. Differences include the availability of personal protective equipment; operational requirements or needs; variations in policies influencing the availability of COVID-19 test kits or related reagents; and approaches to exposure monitoring and contact tracing for healthcare workers. Given the critical role healthcare workers play in the pandemic response, it is essential for policymakers to understand and scrutinize their scientific and contextual rationales. This project aims to inform policy and public health responses to protect healthcare workers. Through research studies in Canada and South Africa, and using comparative data from an ongoing multi-country study, the team will generate findings to determine what works to protect healthcare workers, in which contexts, using which mechanisms, and to achieve which outcome. These findings will be shared with decision-makers at local, provincial, national, and international levels and disseminated through academic publications. This project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, which was coordinated by the Canadian Institutes of Health Research in partnership with IDRC and other funders.",,2022,The University of British Columbia,307692,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | IPC in health care settings,2020 +P23350,109553,Improving outcomes in individuals with COVID-19 with renin-angiotensin system inhibition: the COVID-RASi trial,"Cardiovascular disease is among the leading causes of death associated with COVID-19. Elderly patients with a history of heart attack, stroke, hypertension, or diabetes have a significantly higher chance of dying compared to other infected patients. A clinical trial will be launched amongst COVID-19 patients aged 65 and older with at least one of three pre-existing conditions (cardiovascular disease, diabetes, and obesity) to evaluate whether the use of a group of common blood pressure drugs called renin-angiotensin system inhibitors (RASi) may protect high-risk COVID-19 patients. Preliminary evidence indicates that these drugs can be protective in high-risk patients. However, the data looked backwards at past events, which can be fraught with hidden biases. A rigorous, forward-looking trial to evaluate these agents in COVID-19 is thus required. A network of Canadian and international research institutes will evaluate whether adding RASi drugs, compared to no added treatment in high-risk COVID-19 patients, can decrease the chance of dying or requiring ventilators or intensive care units. If results confirm its benefit, using these common and inexpensive medications will potentially save many lives around the world. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2023,Ottawa Heart Institute Research Corporation / Corporation de Recherches de l'Institut de Cardiologie d'Ottawa,858493.87,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2020 +P23351,109554,Validation of rapid molecular testing for COVID-19 and integration with tuberculosis diagnostics,"The COVID-19 pandemic is causing a high burden of disease in Peru and other Latin American countries and affecting the capacity of health services to provide appropriate care to neglected diseases that persist outside the global spotlight. In the Americas, Peru is second only to Brazil in total cases of tuberculosis (TB). Considering that the symptoms of COVID-19 and TB are similar, integrating COVID-19 and TB testing would be an opportunity to improve the quality of patient care. This study will take advantage of existing infrastructure for TB diagnosis in Peru 'Äî which provides cheap, user-friendly, and rapid, automated molecular TB testing 'Äî to validate its use for the diagnosis of COVID-19 in adults with suspected COVID-19 infection in Lima. It will assess the integration of the two diagnoses using a single respiratory sample at a secondary hospital in an area of high prevalence of TB outside of Lima. Strengthening COVID-19 diagnostic capacity and integrating COVID-19 with TB testing will save resources, improve quality of disease care, and minimize transmission time in the community. This project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2023,The Research Institute of the McGill University Health Centre/L' Institut de recherche du centre universitaire de santé McGill,307679.67,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23352,109555,"Effect of an eHealth intervention on COVID-19 knowledge, behaviours, and mental wellness of LGBT+ people: #SafeHandsSafeHearts randomized trial","Marginalized populations around the world bear a disproportionate burden of COVID-19 morbidity and mortality. This is particularly true for LGBT+ groups who already face elevated rates of physical and mental health challenges, as well as socio-structural barriers that limit the effectiveness and feasibility of recommended preventive measures such as physical distancing and handwashing. These health and social disparities greatly increase the vulnerability of LGBT+ people to COVID-19, and compound with other forms of marginalization such as race/ethnicity, gender, age, and HIV status, as well as unstable housing and employment, healthcare discrimination, and violence. There is an absence of coordinated and community-engaged responses to reduce the risk of COVID-19 for these groups. To address these challenges, this project will adapt, test, and disseminate a community-engaged eHealth intervention with diverse LGBT+ populations to reduce their risk of COVID-19 infection. The research team will test the intervention'Äôs effectiveness in increasing COVID-19 knowledge and protective behaviours, and in reducing psychological distress among LGBT+ people in Canada, India, and Thailand. The results of this project will reduce the risk of COVID-19 for LGBT+ people and will also better inform health system and public health responses to support engagement of LGBT+ and other marginalized populations in the pandemic response. The project was selected for funding through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada.",,2022,The Governing Council of the University of Toronto,416309.51,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Digital Health | Gender,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +P23353,109556,A global cohort study to understand the risk factors and long-term health impacts of COVID-19,"Little is known about the behavioural and environmental risk factors of COVID-19 because of a lack of high-quality epidemiological data. Although early reports found associations between COVID-19 and smoking, obesity, and cardiovascular conditions, these findings are not consistent and there is no clear scientific consensus about the underlying risk factors that increase the risk of COVID-19. Moreover, the long-term effects of COVID-19 on cardiovascular and respiratory health are unclear. This project aims to examine the factors that increase or reduce the risk of COVID-19 infection, in addition to the long-term impacts of COVID-19 on respiratory and cardiovascular health. It will study 35,000 adults from 13 countries who have already been recruited into the Prospective Urban Rural Epidemiology Study, an international study assessing the health of 200,000 people from 28 countries worldwide. Participants will be tested for COVID-19 and assessed for behavioural and physical risk factors such as smoking, alcohol use, or low physical activity. Clinical examination and patient monitoring will assess the impact of COVID-19 on respiratory function, as well as on the risk of longer-term cardiovascular or lung conditions. The study findings will provide valuable knowledge on the risk factors of COVID-19 and the potentially harmful long-term consequences of the disease. This project was selected through the COVID-19 May 2020 Rapid Research Funding Opportunity, coordinated by the Canadian Institutes of Health Research in partnership with IDRC and several other health research funding agencies across Canada",,2023,McMaster University,1520472.08,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Post acute and long term health consequences,2020 +P23354,109559,Predictive modelling and forecasting of the transmission of COVID-19 in Africa using artificial intelligence,"Different phases of the COVID-19 pandemic present governments and decision-makers across low- and middle-income countries with distinct challenges. While lockdowns and containment strategies show relative success in curbing the spread of COVID-19, the crippling socioeconomic impacts have put pressure on African governments to relax these public health measures. Integrating the power of artificial intelligence, predictive modelling, and simulations, this project supports data-driven decision-making to prevent and control the COVID-19 pandemic in Africa. It builds on a COVID-19 dashboard and transmission models that have been widely adopted by governments and international organizations. The project will develop modelling tools and simulation dashboards relevant to local health authorities to mitigate the impact of subsequent waves of infection. In addition, these tools will enable the researchers to evaluate the relative effectiveness and potential biases of public health interventions while accounting for local feasibility, cost, and socio-economic impact. Equity considerations are central to both project design and implementation, including active engagement with local communities and high-resolution indicators that incorporate the disproportionate impact of the pandemic on marginalized populations like women, rural communities, and informal workers. Communication strategies with local stakeholders will address dis- and misinformation about COVID-19 prevention and treatment. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, funded by IDRC and the Swedish International Development Cooperation Agency. 'ÄÉ",,2023,York University,936772.5,Other,Not applicable,Not Applicable,Rural Population/Setting,Women | Other,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Disease surveillance & mapping | Communication | Policy research and interventions | Social impacts,2020 +P23355,109577,Responses to COVID-19 through social protection and the strengthening of local food systems: Case of the Niayes in Senegal (COVID19-Agriculture and Food Security),"The COVID-19 pandemic has had a negative impact in the Sahel region of West Africa, which is already facing several protracted crises, including environmental degradation, poverty, conflict, rural exodus, and gender inequality. Although Senegal launched several economic and financial measures to strengthen health systems and support the most vulnerable households, businesses, and the diaspora, large parts of the primary sector were not specifically targeted by these measures and have been suffering. The multidimensional shocks of COVID-19 have reinforced existing vulnerabilities in local food systems and created new ones. The lack of structure and professionalism of agricultural value chains, pervasiveness of informal distribution channels, weak financing, lack of storage and conservation infrastructure, and uncertainties related to product quality, have all been exacerbated by the pandemic. This project will generate knowledge and support tools to improve decision-making for social protection mechanisms and strengthen local food systems in the Niayes region of Senegal. Highly influenced by nearby urban markets, the Niayes region provides a fertile ground for identifying critical points in local food systems that affect the delivery of essential food items to urban, peri-urban, and rural populations. The project will analyze government and stakeholder responses to food and nutrition insecurity, document the impact of government and stakeholders'Äô interventions to strengthen the resilience of food systems, and explore the best way to respond to future shocks and support food systems. This project is supported through IDRC'Äôs rapid research response to the COVID-19 crisis. This response mechanism supports the development of new short-term activities as a supplement to existing projects, to document the impact of the pandemic (and control measures) on local food systems and on food security, to document planned and spontaneous responses to the emerging crisis, and to inform responses to the current crisis and future challenges.",,2021,Initiative Prospective Agricole et Rurale,489450,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Senegal,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Other secondary impacts,2020 +P23356,109578,Impacts of government COVID-19 responses on food systems and livelihoods in the Sahel (COVID-19-Agriculture and Food Security),"IDRC'Äôs response to the COVID-19 crisis includes a rapid response to the pandemic'Äôs food and nutritional security crisis. This response mechanism supports the development of new, short-term activities as a supplement to existing projects. The goals are to document the impact of the pandemic (and control measures) on local food systems and food security, to document planned and spontaneous responses to the emerging crisis, and to strengthen responses to the current crisis. The rapid response mechanism also supports the development of new projects to document and analyze the efficacy of those responses. This will help low- and middle-income countries to respond more efficiently to subsequent waves of the epidemic, as well as potential future shocks. This project will draw lessons from ongoing policy formulation and interventions to mitigate the impact of the COVID-19 crisis in the Sahel. Data and results from the research will enhance risk management and disaster risk reduction methods of national and regional food system policies to be more impact-oriented, with due consideration for gender, youth, and vulnerable groups. It will cover five countries in West Africa: Burkina Faso, Cape Verde, Mali, Niger, and Senegal. Regional initiatives led by the Economic Community of West African States (ECOWAS) will complement these efforts. Main stakeholders in this project include government ministries, the ECOWAS Commission, farmers, herders, input dealers, processors, agricultural product aggregators, wholesalers, and consumers as well as financial and technical partners. The project will pay special attention to the integration of women, youth, and vulnerable groups. The research methodology will include a desk review, online and physical surveys, focused group discussions, key informant interviews, and validation meetings.",,2021,Conseil ouest et centre africain pour la recherche et le développement agricoles/West and Central African Council for Agricultural Research and Development,561450,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Senegal,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P23357,109579,Support project in response to the effects of COVID-19 in the livestock sector in West and Central Africa (COVID-19-Agriculture and Food Security),"IDRC'Äôs response to the COVID-19 crisis includes a rapid response to the food and nutritional security crisis associated with COVID-19. This response mechanism supports the development of new, short-term activities that supplement existing projects. The goals are to document the impact of the pandemic (and control measures) on local food systems and food security; to document planned and spontaneous responses to the emerging crisis; and to strengthen responses to the current crisis. The rapid response mechanism also supports the development of new projects that document and analyze the efficacy of those responses. This will help low- and middle-income countries respond more efficiently to subsequent waves of the epidemic and to potential future shocks. In West and Central Africa, COVID-19-related restrictions on movement within and between countries is affecting food availability and exacerbating the risk of food shortages. Agro-pastoral family farms are among those most heavily affected by these restrictions because they are confined to areas with poor foraging, which drastically reduces the performance of the herd. Governments have proposed measures for the benefit of pastoralists, raising several questions that will be addressed within the framework of this project. These include whether COVID-19 has exacerbated pre-existing vulnerabilities, whether state social measures can reduce vulnerability, and the steps that need to be taken by farmers and decision-makers to mitigate the negative impacts of COVID-19.",,2021,Association pour la Promotion de l'Elevage au Sahel et en Savane,559350,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Burkina Faso,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23358,109580,The impacts of COVID-19 responses on the political economy of African food systems (COVID-19-Agriculture and Food Security),"IDRC'Äôs response to the COVID-19 crisis includes a rapid response to the food and nutritional security crisis associated with COVID-19. This response mechanism supports the development of new, short-term activities that supplement existing projects. The goals are to document the impact of the pandemic (and control measures) on local food systems and food security; to document planned and spontaneous responses to the emerging crisis; and to strengthen responses to the current crisis. The rapid response mechanism also supports the development of new projects that document and analyze the efficacy of those responses. This will help low- and middle-income countries respond more efficiently to subsequent waves of the epidemic and to potential future shocks. This project aims to implement action-oriented research on the impacts of COVID-19 interventions on the functioning and structure of food systems in Tanzania, Ghana, and South Africa. These three countries cover a spectrum of different economies, food systems, and COVID-19 responses. The research team will collect and analyze information across formal and informal food systems using a mixed-methods approach. By mapping food flows, key informant interviews, ethnographic field and online research, and collecting voice notes and video material, the project will gain a real-time understanding of the direct impacts of regulatory responses on production systems, value chains, and formal and informal markets by focusing on women and marginalized actors. The findings will be packaged and disseminated for policy, advocacy, and academic purposes.",,2022,University of the Western Cape,551456,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,South Africa,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23359,109581,"COVID-19, food security, and opportunities for reconfiguring unequal gender relations in Burkina Faso and Senegal (COVID-19-Agriculture and Food Security)","IDRC'Äôs response to the COVID-19 crisis includes a rapid response to the food and nutritional security crisis associated with COVID-19. This response mechanism supports the development of new, short-term activities that supplement existing projects. The goals are to document the impact of the pandemic (and control measures) on local food systems and food security; to document planned and spontaneous responses to the emerging crisis; and to strengthen responses to the current crisis. The rapid response mechanism also supports the development of new projects that document and analyze the efficacy of those responses. This will help low- and middle-income countries respond more efficiently to subsequent waves of the epidemic and to potential future shocks. The COVID-19 pandemic has had a negative impact in the Sahel region of West Africa, which is already facing several protracted crises, including endemic food insecurity. This project intends to assess the impact of the pandemic on food security for poor and vulnerable rural households in Burkina Faso and Senegal and the measures to control it (in terms of food production, access, availability, and stability). The research will provide in-depth knowledge of the challenges of food security and resilience to shocks such as the COVID-19 epidemic, which will help define more effective policies, strategies, and intervention models at national and regional levels.",,2021,Centre for International Studies and Cooperation/Centre d'étude et de coopération internationale,567481.36,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23360,109582,Using artificial intelligence to inform public health responses to COVID-19 in Colombia,"The COVID-19 pandemic is having devastating effects in Colombia, which has experienced over 666,000 observed cases and 21,000 deaths as of early September 2020. The COVID-19 crisis is being called a 'Äúdata-driven pandemic'Äù because massive amounts of information and data are being released and shared at an unprecedented scale. Globally, artificial intelligence (AI) and data science research is showing promise for early COVID detection, timely communications with the public, new diagnostic tools, and informed policy and public health responses that can be automated, implemented, and scaled affordably. This project is a five-pronged interdisciplinary research endeavour, based on AI methods and data science, aimed at developing, implementing, and communicating evidence for COVID-19-related challenges, responses, and recovery in Colombia. The aim is to develop long-term, real-time, gender-specific, and locally relevant mathematical models that will shed light on the possible impact, trajectories, geographical spread, and uncertainties of disease progression, in addition to risk assessment based on socio-demographic, behavioural, and medical history variables. The project will also focus on estimating the effect of COVID-19 on other diseases, particularly on disease incidence, the resurgence of other infectious diseases, changes in chronic disease frequency and severity, gender disparities, and mental health. The project also intends to analyze popular social networks to identify health-related trending interest for vulnerable groups or populations, common reactions to policies and events of social importance, and critical users that act as 'Äúsuper spreaders'Äù for information and misinformation. Finally, the research aims to design communication strategies to confront mis- and dis-information around COVID-19 that are tailored to different groups according to age, gender and regional and socioeconomic characteristics. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, funded by IDRC and the Swedish International Development Cooperation Agency.",,2023,Universidad de los Andes,908250,Other,Not applicable,Not Applicable,Unspecified,Vulnerable populations unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing | Gender,,,Colombia,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Communication | Policy research and interventions | Indirect health impacts,2020 +P23361,109584,Using artificial intelligence for early detection of potential epidemic and pandemic outbreaks after COVID-19 in Argentina,"The COVID-19 pandemic continues to be severe in Argentina. By mid-September 2020, there were 565,000 cases and 11,700 deaths due to the disease. This project seeks to lay the foundations for incorporating artificial intelligence (AI) and data science into the early detection of epidemic outbreaks like COVID-19. It will generate evidence-based preventive public health decision-making, including gendered perspectives, at the national, sub-national, and local levels. The initiative seeks to generate quality data and create the conditions for the progressive implementation of electronic health records at the provincial level. This initiative is structured in four activities. The first aims to develop AI solutions for the early detection of infectious diseases based on existing electronic health record databases. The second activity seeks to expand the functionalities of the electronic health records system in the National Ministry of Health, which is still at an early stage of development. The third activity will implement a pilot of an expanded version of the national electronic health record system in local health centres and hospitals in vulnerable neighbourhoods, with training for health centre staff and a user awareness campaign to secure the success of the strategy. Finally, the project will focus on planning, monitoring, evaluating, disseminating, and documenting the experience. The mitigation of gender biases will be addressed through the development of models that consider fairness strategies in AI. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, funded by IDRC and the Swedish International Development Cooperation Agency.",,2023,"Asociación Civil Centro Interdisciplinario de Estudios en Ciencia, Tecnología e Innovación CIECTI",907650,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing | Digital Health | Innovation,,,Argentina,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health information systems,2020 +P23362,109585,Using artificial intelligence to combat COVID-19 in Senegal and Mali,"Countries in the South generally use control measures and predictive models of COVID-19'Äôs evolution that are imported from the North. However, these approaches use artificial intelligence (AI) technologies and/or data science (contact tracing applications, patient triage) without ensuring their adaptability to local social and cultural contexts. In Senegal and Mali, these technologies raise ethical and legal issues because they can neglect socio-political, economic, and cultural vulnerabilities and they have not been previously considered in local ethical dimensions. This research proposes COVID-19 epidemiological modeling based on the socio-anthropological context in Senegal and Mali. It also addresses the question of the adaptability and social acceptability of AI technologies and health control measures while respecting ethics and human rights. This multidisciplinary research, proposed by a consortium led by Universit√© Cheikh Anta Diop in Senegal, aims to strengthen the capacities and awareness of governments and civil society in Africa to help improve their effectiveness in their fight against pandemics. The intention is to mobilize data science and AI that are ethical, responsible, and adapted to African socio-cultural contexts and that integrate considerations for gender and vulnerable groups. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, funded by IDRC and the Swedish International Development Cooperation Agency.",,2023,Université Cheikh Anta Diop,949401.88,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Data Management and Data Sharing | Gender,,,Senegal,,Epidemiological studies,,2020 +P23363,109586,"Using AI to contain COVID-19 and future epidemics in Malaysia and Sri Lanka with a focus on women, children, and underprivileged groups","The COVID-19 crisis is being called a 'Äúdata-driven pandemic'Äù 'Äì that is, massive amounts of information and data are being released and shared at a scale that has never been seen before. Across the world, Artificial Intelligence (AI) and data science research is showing promise for early COVID detection, timely communications with the public, new diagnostic tools; and informed policy and public health responses that can be automated, implemented and scaled affordably. AI and data science methodologies are particularly well suited to pattern recognition, forecasting, and automation. Dashboards can help to relay risk and hotspots to policy makers, help support at-home self-testing and advice, as well as supporting care practitioners with medical diagnosis and patient triage. AI and data science research should call into consideration the needs of women and other vulnerable groups or may risk exacerbating existing inequalities. This project from the University of Peradeniya in Sri Lanka will use an Artificial Intelligence (AI) framework to assess and contain COVID-19 and future epidemics while mitigating the socio-economic impact to women, children, and underprivileged groups in Malaysia and Sri Lanka. Based on generated behaviour and movements, the project will develop AI to conduct contact tracing and socioeconomic impact mitigation actions in a more informed, socially conscious and responsible manner in the case of the next wave of COVID-19 infections or a different future infectious disease. The project will develop a set of recommendations that policy makers and medical practitioners can access. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, a program funded by Canada'Äôs International Development Research Centre and the Swedish International Development Cooperation Agency.",,2023,University of Peradeniya,635025,Human Populations | Other,Asian,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women | Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,Unspecified,Innovation,,,Sri Lanka,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Policy research and interventions,2020 +P23364,109587,"Leveraging AI and data science techniques in harmonizing, sharing, accessing and analyzing SARS-COV-2/COVID-19 data in Rwanda","Rwanda has been praised for its swift response and coordinated policy efforts to manage the COVID-19 crisis. The government and other public health institutions are calling for initiatives that can support the increased availability of data to support evidence-based policymaking and adjust to the changing pathways of the disease. However, much of the available data is fragmented, incomplete, and scattered across multiple institutions such as clinics, hospitals, and testing sites. In addition, data sharing can be affected by privacy requirements and differing data structures that can make it challenging to gain new insights. This project will pilot an approach to aggregate and harmonize COVID-19 data so that it respects privacy rights and supports new kinds of innovation. The data will be supplemented by additional household surveys. The project will also explore legal and social data rules around data sharing. Finally, the project will use artificial intelligence and traditional modelling techniques to improve understanding and predict the impacts of public health measures on the trajectory of the pandemic in Rwanda. The project will focus on overall infection rates, hospital admissions, the severity of disease, mental health, and other social and economic challenges. It will aim to provide a scalable approach that can be used to address other infectious diseases such as Ebola and influenza. Ultimately, the project aims to support the Rwandan public health ecosystem in harmonizing data and leveraging machine learning to prevent and address infectious diseases. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, funded by IDRC and the Swedish International Development Cooperation Agency.",,,Université du Rwanda,962175,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Data Management and Data Sharing,,,Rwanda,,Epidemiological studies | Health Systems Research,Impact/ effectiveness of control measures | Disease surveillance & mapping | Health information systems,2020 +P23365,109596,Enhancing the design of the Adaptation Futures conference for a more distributed participation in the context of limited international mobility,"Adaptation Futures, convened under the auspices of the United Nations, is the world'Äôs premier gathering of the climate change adaptation research community. IDRC support and engagement have been critical in broadening the participation of researchers from the Global South. Canada was selected to host the seventh edition of Adaptation Futures to be held in Montreal in 2023, a key year that will also see the beginning of a new Intergovernmental Panel on Climate Change assessment cycle and the first global stock-taking under the Paris Agreement. As the world begins to overcome the COVID-19 pandemic, this project will redesign Adaptation Futures to enable more meaningful engagement from the Global South, to better replicate the capacity-strengthening and professional-networking benefits of in-person gatherings, and to reduce the carbon footprint of such gatherings. Combining features of virtual and distributed formats offers the potential for more equitable participation by both women and men, as well as people without the means for international travel.",,,Ouranos Inc.,207775.56,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P23366,109598,Supporting knowledge translation for research on socio-economic responses to COVID-19,"The world has put wide-ranging public health measures and diverse public policies in place to address the spread of COVID-19. The health, social, economic, and political impacts of the global pandemic are now apparent in low-income countries, and they have the potential to widen inequalities, deepen poverty, generate insecurity, undermine governance, and cause lasting effects on capacities to meet the Sustainable Development Goals. There is an urgent need for reliable, contextually grounded local data and evidence to inform appropriate responses to this global pandemic. In response to this need, IDRC launched the Social and Economic Response and Recovery from COVID-19 (SERRC) Initiative, a rapid response funding mechanism that is funding 21 projects. Its goal is to contribute research, evidence, and data for policy and solutions that will mitigate the social and economic impacts of COVID-19 and to promote recovery from the pandemic across Africa, Asia, Latin America, and the Middle East. The research will focus on developing macro-economic policy; supporting essential economic activity by protecting workers and small producers; and promoting democratic governance and effective, accountable responses. This new project will support knowledge translation activities to promote and capture learnings of and beyond the SERRC projects that can guide national, regional, and global policies and actions. This includes identifying potential research users, developing knowledge platforms, peer-to-peer learning and exchange, and capacity development within projects to undertake knowledge translation activities.",,2022,Institute of Development Studies GB,350400,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P23369,109621,Supporting gender-responsive research on socio-economic recovery from COVID-19,"The world has put wide-ranging public health measures and diverse public policies in place to address the spread of COVID-19. The health, social, economic, and political impacts of the global pandemic are now apparent in low-income countries, as is their potential to widen inequalities, deepen poverty, generate insecurity, undermine governance, and leave lasting effects on capacities to meet the Sustainable Development Goals. As wide-ranging measures are being put in place in low-income contexts, there is an urgent need for reliable, contextually grounded local data and evidence to inform appropriate responses to this global pandemic. Women and marginalized groups have disproportionately suffered the negative impacts of the pandemic, which have exacerbated pre-existing vulnerabilities. This project will provide support to research projects to integrate gender and diversity considerations as a crosscutting theme. Using gender-sensitive research approaches and ensuring that research findings contribute to gender-sensitive policy responses to COVID-19 will be key to the success of these projects. Activities will focus on harnessing existing capacity of research teams and peer-to-peer learning at a cohort level. Advisory support will also be available to project teams, with an emphasis on developing a gender-responsive theory of change and appropriate research methods. In response to this need, IDRC launched the Social and Economic Response and Recovery from COVID-19 (SERRC) Initiative, a rapid response funding mechanism that is supporting 21 projects. Its goal is to contribute research, evidence, and data for policy and solutions that will mitigate the social and economic impacts of COVID-19 and to promote recovery from the pandemic across Africa, Asia, Latin America, and the Middle East. The research will focus on developing macro-economic policy; supporting essential economic activity by protecting workers and small producers; and promoting democratic governance and effective, accountable responses.",,,Access Now,25500,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Unspecified,Unspecified,Gender,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2020 +P23370,109622,Harnessing COVID-19 data to support public health and economic decision-making in Kenya and Malawi 'Äì COVID AI,"The emergence of the COVID-19 global pandemic presents serious health and livelihood threats to people in low- and middle-income countries (LMICs) all over the world. There is an urgent need for accurate, real-time data for health policy and planning to combat the threats. In many countries there are methodological gaps in data integration and a lack of information and research capacity to make informed decisions to guide public health policy. The absence of data also makes it difficult to identify vulnerable populations and provide appropriate information to protect and improve people'Äôs health. Moreover, obtaining information can be especially difficult under the restrictions of pandemic lockdowns. Current innovations in AI and data science can support the collection and analysis of real-time, accurate data from multiple data sources. This project proposes to develop the key elements of a coordinated pan-African COVID-19 data ecosystem with a robust suite of data standards, technologies, and data integration methods that leverage AI and data science for analysis and oversight. It will focus on data from Kenya and Malawi because both countries adopted different strategies to combat the COVID-19 pandemic. The goal is to scale the dissemination of information to enhance decision-making and guide the development and implementation of strategies to reduce morbidity and mortality from COVID-19. The project is developing a network of stakeholders to exchange information, experiences, and knowledge that will support data acquisition, management, governance, and reporting; a data tracking system; a common data model; and a comprehensive data hub for COVID-19 data to demonstrate how COVID-19 is affecting transmission dynamics, its impact on health, education, work, transport, and effective interventions. It will also enhance the methodological capacity of data analysts and develop communication strategies for the public, policymakers, and decision-makers.",,,African Population and Health Research Centre,916344,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Data Management and Data Sharing,,,Kenya,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +P23371,109627,Emergence of a female middle class and demand for childcare in West Africa,"Francophone countries in West Africa have experienced positive economic growth rates in recent years that appear to be leading to an expansion of the middle class. To plan accordingly, it is important to shed light on the dynamics of the female middle class and the demand for childcare services. The research from this project will provide relevant evidence, practical tools, and advice for decision-making. Through partnerships with public and private sector actors, it will identify and facilitate the scaling up of effective solutions to achieve women's empowerment and gender equality through the large-scale adoption of tailored childcare models. This will help reduce the domestic burden of unpaid care work for middle-class women, enabling them to fully participate in the economy and reap benefits commensurate with their efforts. The project is part of IDRC's support activities for applied development research in West Africa, and a continuation of the successful initiative on Growth and Economic Opportunities for Women (GrOW). GrOW West Africa's goal is to support applied, practical, in-depth research rooted in the local context of Benin, Burkina Faso, C√¥te d'Ivoire, and Senegal. Its aim is to help rebuild post-COVID-19 socio-economic systems in a way that contributes to women's empowerment and gender equality.",,2023,Université Amadou Mahtar Mbow,381108,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Senegal,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P23372,109630,End-to-end AI and data systems for targeted surveillance and management of COVID-19 and future pandemics affecting Uganda (COAST),"The COVID-19 crisis is being called a 'Äúdata-driven pandemic'Äù 'Äî that is, massive amounts of information and data are being released and shared at a scale that has never been seen before. Across the world, AI and data science research is showing promise for early COVID detection, timely communications with the public, new diagnostic tools, and informed policy and public health responses that can be automated, implemented, and scaled affordably. A key challenge to mounting a coordinated, real-time response has been a lack of representative, high-quality, and timely data systems. Due to the uneven access of under-represented African populations to public and private health care services, gaps in modelling can be created that will further reinforce inequalities in the future. The other core challenge is accessing the necessary data frequently to support real-time systems. If these challenges are not addressed, Uganda will struggle to mobilize new innovations to support the pandemic response or risk implementing solutions that do not benefit communities that are most vulnerable for COVID-19 and future pandemics. This project will focus on strengthening Uganda'Äôs existing health data systems, including combining new data sets such as radio broadcasts, call health records, and data on air pollution to complement existing public health data sets. Researchers will use this data to test and deploy new solutions for patient screening and decision support systems, including a chat bot and automated call-in line to support patients and relieve overwhelmed health officials. The researchers will also test novel approaches to triage COVID-19 patients in a clinical setting, supporting diagnosis and assisting health workers in focusing their attention where they need it most. Finally, they will model and evaluate the impact of COVID-19 public health measures and targeted government responses, analyzing the issues affecting communities and their perceptions of public policy measures, with the aim of influencing positive policies and behaviours. This work will be carried out as part of the COVID-19 Global South Artificial Intelligence and Data Innovation Program, a program funded by IDRC and the Swedish International Development Cooperation Agency.",,,Makerere University,979600,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Data Management and Data Sharing,,,Uganda,,"Epidemiological studies | Policies for public health, disease control & community resilience | Health Systems Research",Impact/ effectiveness of control measures | Approaches to public health interventions | Health service delivery,2021 +P23373,109638,Enhancing the effectiveness of government procurement programs in achieving women'Äôs economic empowerment,"Public procurement is one of the most strategic mechanisms for socio-economic empowerment and it is at the front line of the wider governmental response to the COVID-19 pandemic. It presents a clear opportunity to advance women'Äôs economic empowerment and when used strategically, it can significantly contribute to building a more resilient and sustainable economy and society. The Kenyan government introduced the Access to Government Procurement Opportunities (AGPO) program, mandating that 30% of government procurement come from women, youth, and persons with disabilities. Despite this initiative, uptake by these groups is very low at 7%. This project seeks to uncover barriers and determine how AGPO can be mobilized as an instrument for boosting women'Äôs economic empowerment, particularly in the COVID-19 recovery. Using a mixed-methods approach, this project will evaluate AGPO and other relevant public procurement programs in Kenya in five key areas: relevance, effectiveness, efficiency, sustainability, and impact. It will also identify scalable solutions and the public and private sector actions required to make these programs more effective. The goal is to enhance Kenyan women'Äôs access to and participation in public procurement opportunities to boost their economic outcomes and address the gender equality gap. As public procurement will play a key role in governmental responses for the post-crisis recovery, this project will make an important contribution to building back better and more gender inclusive. This project is supported by the Growth and Economic Opportunities for Women (GrOW) East Africa initiative, jointly funded by the Bill & Melinda Gates Foundation, The William and Flora Hewlett Foundation, and IDRC. GrOW East Africa seeks to spur transformative change to advance gender equality in the world of work.",,,Strathmore University,384888,Human Populations,Black,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Kenya,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P23374,109640,Empowering women through provision of quality childcare services,"Women'Äôs participation in the labour market is an important vehicle for increased gender equality and economic empowerment. One of the key challenges for women in Kenya, as in many low- and middle-income countries, is inadequate childcare support. Women spend triple the amount of time on unpaid care work compared to men, further contributing to wage inequality and lower productivity. Lack of childcare support compounds women'Äôs disadvantage and further exposes them to economic vulnerabilities. COVID-19 has exacerbated this situation. Finding innovative solutions to this barrier is a key ingredient to achieving many of the Sustainable Development Goals. While there is growing evidence that affordable childcare boosts the participation of poor working mothers in paid employment, little is known about what models are effective and scalable in low-income contexts. This project will be carried out in Nakuru County in Kenya and will assess the potential of a ""hub & spoke'Äù model of early childhood development as a scalable model for enhancing the economic outcomes of women in low-income communities. It will establish one hub and 20 spokes, with an embedded knowledge platform to generate insights on program effectiveness and scalability. It will actively engage key stakeholders both at the county and national levels throughout the project cycle to ensure findings from the research inform government policies for building back better in the COVID-19 recovery efforts. This project is supported under the Growth and Economic Opportunities for Women (GrOW) East Africa initiative, jointly funded by the Bill & Melinda Gates Foundation, The William and Flora Hewlett Foundation, and IDRC. GrOW East Africa seeks to spur transformative change to advance gender equality in the world of work.",,,African Population and Health Research Centre,540360,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Kenya,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Social impacts | Economic impacts,2020 +P23375,109643,From promises to action: shifting gender norms and public perceptions about unpaid care work in workplaces and families in Uganda,"Unpaid care work, which is disproportionately carried out by women because of unequal gender and social norms, is often invisible and undervalued in policy and economic contexts despite its fundamental importance to the functioning of society. With added childcare responsibilities following school closures due to the COVID-19 pandemic and the rising demand to care for the sick, women continue to shoulder much of society'Äôs unpaid care work. In Uganda, while women are increasingly participating in the labour market, unpaid care work remains a key barrier to further advances in this area. In 2018, women'Äôs participation in paid work was 44.9% compared to 53.7% for men. COVID-19 is expected to widen the gap. Shifting such norms and enhancing the redistribution of care responsibilities by fostering male engagement is essential for achieving gender equality in the world of work. It is also integral to efforts to build back better as governments and the international community respond to the fall-out of the COVID-19 pandemic. Using a mixed-methods approach that combines randomized control trials with qualitative insights, this project will explore what works and what is scalable in shifting gender norms, public perceptions, and attitudes related to unpaid care work and gender-based violence in Uganda. This project is supported under the Growth and Economic Opportunities for Women (GrOW) East Africa initiative, jointly funded by the Bill & Melinda Gates Foundation, The William and Flora Hewlett Foundation, and IDRC. GrOW East Africa seeks to spur transformative change to advance gender equality in the world of work.",,,Economic Policy Research Centre,546078,Human Populations,Black,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Uganda,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts,2020 +P23377,109673,"Growing public debt, debt relief, and sustainable inclusive recovery","The economic impacts of the COVID-19 pandemic continue to expand, and the ability of lower-income countries to implement policies has been limited. This is further constrained by growing levels of public debt, which have been compounded by increased spending related to climate disruptions such as floods, droughts, and other extreme weather events. This situation is leading to calls and initiatives for debt relief to help developing countries progress towards the Sustainable Development Goals (SDGs) and the commitments related to the Paris Agreement on climate change. However, current commitments remain short-term and are likely to be insufficient. There is limited discussion on how the growth of debt is impacting investments to achieve the SDGs and Paris commitments. Knowledge gaps exist regarding how growing debt is impacting policy choices; how sovereign debt can be swapped for climate commitments, and how such swaps can be implemented; and what impacts (if any) the debt situation has on innovative financing instruments and standards for sustainable investment. IDRC is currently supporting 40 organizations under 21 initiatives to provide policy advice for responses to the pandemic. Six of the projects focus on macro-economic policies, highlighting the limited fiscal means and policy space for low-income countries. This project will examine the evidence they produce to explore research directions and assess research capacity for building locally relevant solutions to debt that helps build a sustainable and inclusive recovery. It will contribute to deepening IDRC'Äôs understanding of the rapidly evolving debt crisis and help ensure that findings around the impact of debt on policymaking are adequately integrated in the program'Äôs research agenda.",,2021,African Forum and Network on Debt and Development,23937,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Zimbabwe,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P23380,109773,Improving maternal and child health for ethnic minority women in Vietnam at scale using digital health,"Despite progress made by Vietnam on improving access to sexual, reproductive, and maternal health services, vast inequalities exist between ethnic minority populations and the majority Kinh population. The emergence and virulent nature of COVID-19 has further exacerbated gender inequalities and health outcomes for pregnant women, new mothers, and newborns. Constituting about 15% of the population, ethnic minority groups suffer higher maternal and infant morbidity and mortality rates and lower life expectancy, and their children experience disproportionately high rates of under-nutrition and stunting. Ethnic minority populations live predominantly in remote mountainous regions, making access to timely, tailored, and quality health services difficult. This project will adapt and develop a strategy to scale up a successful digital health intervention previously funded by IDRC to improve maternal and child health outcomes among ethnic minority populations. The project will be designed incrementally to ensure that the feasibility, acceptability, and sustainability of the approach is optimized, and that the voices and needs of women and commune health workers are integrated into the design and implementation. A strong focus is placed on shifting adverse gender norms and enhancing the agency of ethnic minority women to access quality health services, which includes addressing the specific contextual realities experienced during the ongoing COVID-19 pandemic. The project will explore relevant and ethical use of artificial intelligence to enhance positive changes in behaviours, gender norms, and health outcomes. Expected outcomes of the project include improved awareness, knowledge and health outcomes of women and newborns, stronger bonds between ethnic minority women and commune health workers, engagement of men and other family members, improved practices for government to address ethnic minority women'Äôs maternal and child health needs, and enhanced research capacities, particularly for emerging women researchers. Expected outputs include open-access peer-reviewed articles, the scaled-up digital solution, reusable and translated sexual, reproductive, and maternal health text messages available for others to use, policy briefs, and popular media (such as blogs, social media, and news media) pieces about the project.",,,"Institute of Population, Health and Development",570240,Human Populations,Asian,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Women | Minority communities unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,Unspecified,Gender,,,Viet Nam,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Other secondary impacts,2021 +P23381,109780,Land restoration for post-COVID-19 rural and indigenous women'Äôs empowerment and poverty reduction in Cameroon,"This project seeks to inform policy and/or business practices that foster women and minority groups'Äô participation in, and benefits from, land restoration initiatives in a post-COVID-19 context. It considers a cross-section of hot spots for land restoration from three agro-ecological zones identified in Cameroon'Äôs strategic framework. These zones cover the diversity of factors likely to play out for women'Äôs empowerment in landscape restoration, including agroecology, land uses, land and tree tenure, the role of women and minority groups affected by culture and religion, history, and ongoing initiatives of land restoration, as well as the actors involved. The project will also target Cameroon'Äôs restoration commitment, its National Adaptation Plan, and its nationally-determined contribution to limit global warming as set out in the Paris Agreement. Once constraints and opportunities are identified, the project will promote gender-sensitive business and tree-based restoration options that would be less affected by COVID-19 or other pandemics. It will also inform strategies to scale up best land restoration strategies and practices through documentation and capacity building among key actors, including policy makers.",,,Centre d'Appui aux Femmes Et aux Ruraux,562954,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Indigenous People | Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Cameroon,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P23382,109782,Opportunities for blue economic empowerment and COVID-19 resilience of fisher women in Kenya,"Seaweed and fish farming have opened new livelihood opportunities for women and men in Kenya in recent years. However, structural and socio-cultural barriers prevent women's access to inputs, value addition, finance, skills, and market access. These challenges have deepened due to the onset of the COVID-19 pandemic. This project will contribute towards a resilient and inclusive recovery by providing evidence on how the 'Äúblue economy'Äù (based on marine and coastal resources) can be harnessed to drive sustainable recovery efforts and how supportive policies and investments can be directed to those that need it the most. The project will test and adopt climate-smart integrated multi-trophic aquaculture (IMTA) of seaweeds and fish to improve livelihoods and resilience of fisher women in Kenya'Äôs coastal region, with case studies in Kwale and Kilifi counties. It will engage beach management units, technological institutions, women'Äôs groups, the private sector, and policymakers to study, co-design, and deploy model IMTA farms, and use them as platforms to gain practical insights. It will promote knowledge translation, dissemination, and learning for IMTA systems upscaling, climate change, and COVID-19 response strategies for the local community in Kwale and Kilifi counties, as well as other coastal communities in Kenya.",,,African Centre for Technology Studies,773331,Human Populations,Unspecified,Unspecified,Unspecified,Women | Minority communities unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Kenya,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Economic impacts,2021 +P23383,109807,"Surveillance, control and prevention of neglected zoonotic diseases in Uganda","Despite substantial human, social and economic cost, Rift Valley fever, Crimean-Congo haemorrhagic fever and brucellosis have been long neglected and, as a result, we lack good understanding about the natural history of these diseases and the strategies for mitigation and control. Another gap in knowledge is how these infections are understood by the affected communities, which practices and behaviours make them zoonotic (transmissible to humans), and what the best one-health approaches are to limit the risk of spillover events to humans. The overall objective of this project is to improve understanding and control of these diseases at the human-animal-wildlife interface in the cattle corridor of Uganda. This project will investigate the disease burden in humans, animals and wildlife and will characterize the disease dynamics and drivers across geography, habitat, population density and economic activity. It will also investigate how gender and population-level inequalities shape local transmission dynamics for these diseases. Finally, it will develop a one-health approach (integrating people, animals and ecosystems) to enhance surveillance and reporting systems for these diseases and other zoonoses of global significance. A series of mixed-methods research studies will be conducted in diverse agricultural systems which interface with conservation areas within the Uganda cattle corridor. The project will specifically target sites with a history of the three targeted zoonotic outbreaks, providing an opportunity to study transmission dynamics and networks of these diseases in the multi-ethnic communities in relation to gender, animal markets and diverse agricultural systems. It will provide an understanding based on farming practices, land use, interface of humans and animals in wildlife and forest environments, gender inequalities and other socio-economic factors. One-health models incorporating well-evidenced interventions to mitigate these diseases and their drivers will be developed to strengthen preparedness and responses.",,,Uganda National Health Research Organization,3603132,Animals | Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Other,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Uganda,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping,2021 +P23384,109810,"West African One Health actions for understanding, preventing, and mitigating outbreaks","Human pressure on the environment and climate change have increased the possibility for multi-species contact, zoonosis (the transmission of disease between animals and humans), and the emergence of infectious pathogens and outbreaks. This includes Ebola virus disease and Lassa fever, which have created serious challenges in West Africa. Their recurrence poses multifaceted threats in the region, exacerbated by the COVID-19 pandemic and its economic impacts. This project will accelerate and expand actions to prevent and mitigate infectious disease outbreaks at community and national levels across West Africa with a deeper knowledge of socio-ecological drivers, impacts, and solutions at the human-animal-environment interface. This is known as the One Health approach. The research will be conducted in Sierra Leone, Guinea, Liberia, and Nigeria by an international and multidisciplinary consortium. Gender-responsive, mixed methods will be used, including remote sensing, machine learning, and qualitative methods, to determine relationships between changing demographics, land-use patterns, and emerging pathogens. This will strengthen modelling and prediction of disease hotspots. It will also enrich understanding of the animal-human-animal transitional processes of disease emergence. The research teams will describe and differentiate between the four countries regarding the impacts of COVID-19, Lassa fever, and Ebola virus disease on livelihoods, health systems, gender equality, ecosystems, socio-cultural practices, and food security. Gender-transformative community action groups will be developed to innovate with agricultural and social practices to monitor and mitigate against zoonoses and emerging pathogens. At the national level, the project aims to develop multisectoral, One Health governance structures that can develop environmental and agricultural policies to mitigate against disease emergence and transmission and related risks to food security and social inequities.",,,Njala University,3457485,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Arenaviridae | Coronavirus | Filoviridae | Novel Pathogen,,,,,,,,,Lassa fever | COVID-19 | Ebola virus disease | Disease X,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Sierra Leone,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Disease surveillance & mapping | Policy research and interventions,2021 +P23385,109811,One Amazon: A one-health assessment of emerging epidemic threats and resilience among Amazonian indigenous peoples,"Amazonian indigenous peoples face mounting pressures over their territories, livelihoods, and cultural survival, and they face the threat of new epidemics emerging from human-animal-environment interactions. Food security and nutritional conditions are part of a set of complex interrelated factors crucial in the vulnerability and resilience to these epidemic threats. The recent COVID-19 pandemic provides a good example of how severely Amazonian indigenous peoples can be impacted by pandemics. It also demonstrates their resilience. When public health systems proved insufficient, communities organized themselves to contain propagation and assist the ill using traditional health knowledge. Indigenous women assumed crucial roles as caregivers, but they did not have adequate protection against the virus. Information on the incidence and evolution of the pandemic and indigenous community responses is largely absent from official records and is therefore not informing preparedness programs. This project aims to document the risk and vulnerability of Amazonian indigenous peoples in the face of emerging zoonotic (animal-to-human transmission) epidemics and contribute to their resilience. It will do so by producing localized evidence of the multi-dimensional underlying factors, co-developed with indigenous communities in Colombia, Ecuador, and Peru. It will also strengthen monitoring and early warning through community-based health surveillance programs and training. Social and interdisciplinary research applying participatory action-research methodology will be undertaken in nine rural communities and one urban indigenous group in each country, representing a range of possibilities regarding territorial and food security and sovereignty, cultural diversity, and exposure to outside threats and pressures. It will also promote the transformation of gender and intersectional inequalities (such as age, ethnic identity, etc.) influencing risk, vulnerability, and resilience to epidemics.",,,Instituto del Bien Común,2511000,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Peru,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Animal source and routes of transmission | Disease transmission dynamics | Disease surveillance & mapping | Community engagement | Economic impacts,2021 +P23387,109835,Promoting Latin American engagement in research collaborations for recovery via the Trans-Atlantic Platform for Social Sciences and Humanities,"This project enables increased participation of Latin American research institutions, in collaboration with their national science granting councils, in the Trans-Atlantic Platform (T-AP) call for proposals on Recovery, Renewal and Resilience (RRR) in a Post-Pandemic World. T-AP brings together humanities and social science research funders from South America, North America and Europe to enhance transnational dialogue and collaboration in addressing common challenges. The focus of the RRR call is to fill knowledge gaps on the medium- and long-term impacts of the COVID-19 pandemic to mobilize inclusive and sustainable recovery strategies, through transnational and interdisciplinary collaborations. This project will support the participation of four universities in Colombia, Costa Rica and Peru to join three international research collaborations on: community action and decentralized governance; pandemic recovery needs in marginalized communities of Latin America; and a green and inclusive post-pandemic recovery of the blue economy (sustainable use of ocean resources for economic growth) and coastal communities. They will join colleagues from Brazil, Canada, Germany, the United Kingdom and the United States, supported by their respective national granting agencies. These collaborations aim to enhance the voices of marginalized communities and deepen understanding of social mobilization strategies. They also aim to strengthen research capacities in young students through peer-learning and knowledge-exchange activities. In addition, they aim to increase the capacity of policymakers to implement evidence-based recovery strategies through effective synthesis and communication of research findings.",,,Universidad de Costa Rica,457626,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Costa Rica,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23388,109873,Supporting knowledge translation for research on COVID-19 Responses for Equity (CORE) Ã∂ Phase 2,"The health impacts of COVID-19 are now apparent in low-income countries, as are the social, economic and political impacts, as well as the potential for these to widen inequalities, deepen poverty, generate insecurity, undermine governance and leave lasting effects on capacities to meet the Sustainable Development Goals. As wide-ranging measures have been put in place in low-income contexts, there is an urgent need for reliable, contextually grounded local data and evidence to inform appropriate responses to this global pandemic. A rapid-response funding mechanism is now supporting 21 projects to contribute research, evidence and data for policy and practice solutions to mitigate the social and economic impacts of COVID-19 and promote recovery from the pandemic across Africa, Asia, Latin America and the Middle East. A mix of single-organization and consortium projects will generate research to inform immediate, medium-term and longer-term measures that leverage opportunities to 'Äúbuild back better'Äù by generating policies that are more robust and practices that are more effective and equitable. These projects work across three thematic focus areas: macro-economic policy; supporting essential economic activity, protecting workers and small producers; and promoting democratic governance and effective, accountable responses. In addition to these rapid-response research projects, the COVID-19 Responses for Equity (CORE) initiative will support a second phase to design and implement a knowledge-translation strategy to promote and capture learning from and beyond individual projects. This second phase will emphasize synthesis of findings and positioning of southern voices and leadership in national, regional and global policy spaces. The project will also include a second round of reflective learning on practice to deepen findings on rapid-response pandemic support of this kind.",,,Institute of Development Studies GB,412380,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P23390,109901,Establishing a regional platform for evidence-based epidemic and pandemic preparedness in the Middle East and North Africa,"Global disease outbreaks have been heavily influenced by several factors, including climate change, urbanization, globalization, overpopulation and changing human-animal interfaces. These phenomena have produced a wide range of impacts on humans. The Middle East and North Africa has experienced outbreaks in the recent past such as the 2009 outbreak of influenza A (H1N1), MERS-CoV in 2012, a devastating cholera epidemic in Yemen since 2016, and, most recently, the COVID-19 pandemic. While most countries in the region have national capacity for rapid investigation and response to public health threats, COVID-19 exposed fragmented, weak and inadequately resourced health systems. These vulnerabilities affect all aspects of health systems, including, but not limited to, supply chains, essential medicines, laboratory capacity, a trained health workforce and digital infrastructure, which consistently affect the most disadvantaged groups the most disproportionately. To contribute to better pandemic preparedness and response in the region, this project will establish an interdisciplinary and intersectoral program to generate and promote region-specific evidence and its application. Priority focus areas include supporting reliable information systems, strengthening health workforce capacity, seeding and nurturing collaborations and responsive governance mechanisms, and systematically addressing gender inequalities and other forms of exclusion. Expected outcomes include improved evidence-based health policy and decision-making for epidemic and pandemic preparedness and response; enhanced workforce capacity; strengthened analysis and integration of gender equality and inclusion within governance mechanisms, policies and practices; and a regional data portal to both support evidence-based pandemic preparedness and response and reduce misinformation.",,,American University of Beirut,777546,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Unspecified,Data Management and Data Sharing | Gender,,,Lebanon,,Health Systems Research,Health information systems | Health leadership and governance | Health workforce,2022 +P23392,109910,Supporting a tool for tracking and prioritizing global research funding for pandemic preparedness and response,"The COVID-19 pandemic exposed significant problems with traditional funding and research structures in a pandemic response context, leading to slow research activation and duplicate efforts globally. The urgency and scale of research needs have been difficult to respond to and coordinate. Further, the global distribution of COVID-19 research funding and activities has been uneven, with the majority of research projects taking place in high-income countries despite the heavy health and socio-economic burden that the pandemic has placed on low- and middle-income countries (LMICs). The need to map research funding to global and regional prioritization strategies was identified early in the pandemic. A COVID-19 Research Coordination and Learning Initiative (COVID CIRCLE) was established to align and strengthen research response in, with and for LMICs. A key success of COVID CIRCLE was the COVID-19 Research Project Tracker, a live database of funded COVID-19 research projects that aim to help funders and researchers identify gaps and opportunities and inform future research investments or coordination needs. Building on that success, this new project seeks to develop and run a tool and associated analytical capability on global funding data for a wide range of epidemic-prone diseases and broader epidemic and pandemic research preparedness activities on an ongoing basis. This will support coordination of research preparedness and research responses during new epidemics, especially across LMICs.",,,The Chancellor Masters and Scholars of the University of Oxford,307923,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,Health Systems Research | Research on Capacity Strengthening,Health leadership and governance | Cross-cutting,2022 +P23394,109919,"Promoting resilience, preparedness, adaptation and response in 4C (COVID-19, conflict, climate change and rising cost-of-living) emergencies","The complex 'Äú4C'Äù crises 'Äî the COVID-19 pandemic and other epidemics, conflict, climate change and the rising cost-of-living 'Äî put major strain on the health and nutrition of women and children globally and highlight major challenges in emergency preparedness, prevention and response measures. Poverty and food insecurity, coupled with extreme weather events, are at the core of health systems being further weakened during the pandemic. Developing resilience is crucial to ensure that communities mitigate, adapt to, and recover from shocks and stresses. Translating guidance into policy for change is also imperative. The overall goal of this work is to inform efforts to improve national, regional and global capabilities for planning and implementing preparedness, promoting resilience and adapting (PRA) in complex 4C crises within the context of the Sustainable Development Goals. Working with regional expert teams, this project strives to develop a conceptual/analytical framework to map evidence gaps and lessons learned, identify key lessons for preparedness, suggest strategies, develop regional implementation research agendas to address PRA-related evidence gaps, and establish/expand partnerships to answer key PRA implementation research questions through local collaborations. This will inform efforts to improve capabilities in the areas of translating knowledge, planning and implementing capacities and practicing preparedness at the national, regional and global levels. The research will support enhanced partnerships and collaborations in preparedness implementation at regional and country levels that will recommend strategies linking climate change adaptation and sustainable development, particularly for the health of vulnerable groups, as one continuum of all-hazards preparedness. Project results will establish a prioritized research agenda to better implement preparedness and maintain essential health service delivery at the country and global level. This three-year research project will be carried out by a global research consortium led by the Sick Kids Hospital and Aga Khan University. 'ÄÉ",,,Hospital for Sick Children,562500,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,,,2023 +P23397,110012,Economic and health impacts of COVID-19 pandemic on adolescent girls working in artisanal and small-scale mining sectors in Uganda and Ghana,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. These trends affect the artisanal small-scale mining of gold in Uganda and Ghana, which is on the rise. While all people involved are vulnerable due to the often informal and unpaid nature of the work, cultural practices and traditional gender roles mean that adolescent girls in these communities are especially marginalized. This project will assess the economic and health impacts of the COVID-19 pandemic on adolescent girls living in unplanned mining communities in Uganda and Ghana. A detailed list will be produced of interventions that can strengthen coping skills and foster resilience during pandemic recovery. The project will provide policymakers and programmers with a prototype process and a co-developed intervention that can be used as a base for future policies and programs to reduce gender-based inequalities in this sector. This project is funded under the Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Makerere University,759357.04,Human Populations,Black,Adolescent (13 years to 17 years),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Uganda,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P23398,110013,Women rise together across the life course (Write-life),"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks, and made unstable work relationships even more precarious, especially for women. The pandemic also highlighted the disproportionate and longstanding health inequities faced by women and older persons 'Äî populations among the most vulnerable to structural conditions over which they have little or no control, especially in low- and middle-income countries. These inequalities centre on fundamental human rights: water and food security, access to education and healthcare. This project will use an innovative methodology that privileges the voices of women from all socioeconomic backgrounds to explore how women'Äôs health and work have been impacted by the pandemic and to discern their health and well-being issues and needs. The knowledge gained will inform policy and practice to empower women and address the socioeconomic and health inequalities sharpened by the COVID-19 pandemic in Kenya and Uganda. The project aims to increase the participation of women in economic activities and in education; improve policies and practices that benefit women of all ages, particularly in the education, health and employment sectors; increase women'Äôs access to reliable pensions and geriatric healthcare services; strengthen South-South collaboration; and build capacities for three post-doctoral fellows and six graduate students. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,COHEducation and ScienceU Community Health Support Programme,714470.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Kenya,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P23399,110014,Ukuvula Isango: women's empowerment and post-pandemic reconstruction in rural South Africa,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will address key issues related to these impacts in rural areas in South Africa during the COVID-19 pandemic as a starting point for post-COVID-19 rebuilding. The research team will document and explore women'Äôs lives before and during the pandemic to identify trends and triggers that elevate or decrease their livelihoods and health statuses. In the second phase, the project will use this analysis to explore strategies to enhance prevention in both the health and livelihood spheres. The project will generate locally sustainable strategies for future external shocks, such as pandemics, that are women-managed and are less dependent on the state and the biomedical system. Further, innovative approaches will be developed by co-producing solutions by local women and other stakeholders that will 'Äúrebuild better'Äù public health and livelihood strategies. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global, action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada",,,Human Sciences Research Council ZA,680370.46,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,South Africa,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Economic impacts,2022 +P23400,110015,Post-COVID-19 recovery: Overcoming economic hardship and violence against women in southern Benin,"The COVID-19 pandemic and efforts to contain it have threatened livelihoods, introduced new occupational risks and increased the precariousness of labour relations, especially for women. At the beginning of the pandemic, in addition to the recommended preventative measures, Benin established a ""sanitary cordon"" that separated the south from the hinterlands to reduce the spread spread of the virus. These measures also slowed economic activities and disrupted social relations at all levels. Women have been particularly affected and were victims of an upsurge in gender-based violence. The overall objective of the project is to study the differentiated effects of COVID-19 and the sanitary cordon by gender and among women's socio-economic groups, shedding light on the increased risks of multifaceted violence they have faced. Combining quantitative and qualitative methods, the project will use primary and secondary data sources and various collection techniques such as surveys and individual and group interviews. Expected results include contributing to policy formulation and guiding government interventions for gender equality and gender-based violence. In addition, the project will strengthen the capacities of the next generation of women in research and intervention through the awarding of scholarships to women for training in Benin and Canada.'ÄØ This project is funded by the Women RISE initiative (Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable, and Equitable), funded by IDRC, the Canadian Institutes of Health Research and the Social Sciences and Humanities Research Council of Canada. The initiative aims to support gender-transformative and action-oriented research conducted by teams of researchers from low- and middle-income countries and Canada. 'ÄÉ",,,Université d'Abomey-Calavi,708173,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Benin,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2022 +P23401,110016,"Endemicity, care and gender: towards developing resilience in Malaysia'Äôs essential care workforce and infrastructure","The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will study the experience of women performing paid and unpaid work during the COVID-19 pandemic and assess the effectiveness and relevance of policies that govern their working conditions during the pandemic. It will examine the burden of care work (both formal and informal, paid and unpaid) across Malaysia and consider social identifiers using an intersectional lens. These identifiers include ethnicity, gender and class across a spectrum of essential care workers residing in various household and familial configurations. The data generated will be participatory, guided by feminist research principles and collected through in-depth interviews, quantitative surveys, focus group discussions and policy assessments. This work will enhance the capacity of community-based researchers in conducting, analyzing and interpreting research for use in policy processes. In addition, engagement with key government stakeholders will increase their understanding of the gendered impact of COVID-19 on the care sector and equip them with evidence-based policy options on how to ensure resilience and sustainability of the care sector in times of crisis. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,"Women's Aid Organisation, Malaysia",770000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,Unspecified,,,,Malaysia,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts | Economic impacts,2022 +P23402,110017,Gender inequality and rural women'Äôs health in post-COVID-19 Nigeria: towards inclusive and sustainable rural women'Äôs health in Nigeria,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will examine the context-specific challenges that impact women'Äôs lives before, during and after the COVID-19 pandemic using traditional data collection techniques, life histories and photovoice sources. This information will be used to generate robust policy-relevant evidence to promote the integration of innovative strategies on gender equality and women'Äôs access to essential health services into gender-transformative policies on COVID-19 response and recovery. The research will be carried out in Nigeria'Äôs Edo and Delta States. Among the expected results are new knowledge on women/girls'Äô lives and status in rural communities and the impact on their access to essential health services before, during and after COVID-19; a tested framework of community-led initiatives to promote rural women'Äôs economic and health empowerment that is ready for scaling up; at least 50,000 women with improved access/use of essential health services; and at least 2,000 policymakers and non-state actors empowered on the integration of gender equality in COVID-19 recovery programs. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its goal is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Incorporated Trustees of Centre for Population and Environmental Development,769854.47,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,,,Nigeria,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2022 +P23403,110019,Women migrants'Äô health and work after COVID-19: an intersectional and comparative study in Malaysia and Thailand,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will examine the gendered experiences and resilience strategies of women migrants in Malaysia and Thailand in terms of work, health and healthcare access related to COVID-19. The study will focus on the intersectional aspects of gender inequity, migration, labour and COVID-19 that shape health and human rights among women migrants. It will encompass four sites involving 1,000 women and assess differential and shared experiences between migrants with documented/formal and undocumented/informal statuses. The evidence generated will inform gender-transformative policies and interventions for women migrants in Thailand and Malaysia. Using community-engaged processes, the research will create opportunities for migrant women'Äôs empowerment. The project will also build institutional capacity in the participating academic and civil society organizations on gender-transformative research. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,The Governing Council of the University of Toronto,743582.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Economic impacts,2022 +P23404,110020,Addressing the challenges and constraints of social protection policies for Peruvian women domestic workers,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. Using a community-based participatory action research approach, this project will work with women domestic workers'Äô unions to examine the working conditions and access to healthcare of women domestic workers in three cities of Peru (Lima, La Libertad and Piura). More specifically, it will assess and compare the health and working conditions of women domestic workers before and during the pandemic and identify the barriers that affect their access to social protection policies in the formal and informal economies. The goals are to co-design context-adapted recommendations to improve access to health services and social protection among women domestic workers; develop recommendations to respond to the specific needs and contexts of certain groups (by age, ethnic/race identification, migration status); and to strengthen multidisciplinary research team capacities, including early career researchers and women scientists. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Unity Health Toronto,580335.24,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P23405,110021,Improving the integration of women and adolescent girls in the informal sector into pandemic response measures,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will address the involvement of women and adolescent girls in the informal sector in developing response measures to pandemics. To achieve this, the team will conduct an analysis to assess the degree of inclusion of adolescent girls and women in the definition of economic and mental health response measures to the pandemic. Once the assessment is completed, the team will co-develop and implement more inclusive strategies in response measures with all stakeholders. Thirdly, the team will assess the implementation and costs of the co-constructed strategies. The project will provide a better understanding and improve integration of the basic needs and interests of adolescent girls and women in the informal sector in post-pandemic COVID-19 response strategies and in programs that respond to health crises more generally. A series of outputs, including scientific papers and policy briefs, will be produced. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada",,,Université du Québec en Outaouais,638573.32,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2022 +P23406,110022,Catalyzing women'Äôs involvement in post-COVID-19 recovery through agricultural cooperatives in Kenya (WINRACK),"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project seeks to explore how COVID-19 has affected women'Äôs work and health within the agricultural cooperative ecosystem in Kenya. The research team aims to enhance knowledge on how economic changes resulting from COVID-19 disproportionately affect women and women'Äôs health, and how recovery strategies can be inclusive, gender-transformative and health-promoting for women. The findings of the study will inform the design of a health financing intervention in cooperatives. The project is expected to result in a 20% increase in women's membership in agricultural cooperatives and access to credit, a 20% increase in women'Äôs access to healthcare services, the increased capacity of ten local organizations supporting cooperatives, and the strengthened institutional and human personnel capacity of cooperatives to enhance their performance. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.'ÄØ'ÄØ",,,University of the Fraser Valley,757351.4,Human Populations,Black,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P23407,110023,Chamas for Change: gender-responsive and microfinance-based approach to empowering women and building resilience to health emergencies in Kenya,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will assess the impact of Chamas, a community health volunteer-led program that engages women in pregnancy and the first 1,000 days of their children'Äôs lives, to determine whether participation in its programs mitigates the effects of the COVID-19 pandemic on women'Äôs and children'Äôs health and economic well-being. Among these programs are health education, peer support and access to financial capital. Findings from the research in Trans-Nzoia County, Kenya will guide the scale-up of the Chamas program to improve the health and well-being of women and strengthen equitable recovery, gender-transformative policies and preparedness for future health emergencies. The expected results include an adapted or strengthened Chamas for Change program that promotes resilience and mitigates the negative health and economic effects of COVID-19 among women; strengthened social, financial and insurance policies and practices to better serve the needs of women during the pandemic and future health emergencies; and improved access to maternal, newborn and child health services. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,The University of British Columbia,742474.81,Human Populations,Black,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Economic impacts | Health service delivery,2022 +P23408,110024,Innovation in resilience to trauma programming for fostering women'Äôs post-pandemic recovery in El Salvador,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will explore women'Äôs resilience to trauma as a framework for fostering post-pandemic recovery and addressing violence, gender inequalities and social and economic development in El Salvador. The study includes an environmental scan of trauma and resilience-focused programs, policy and practice analysis, in-depth interviews, and focus groups. The expected outcomes include a strengthened network of government, practitioner and academic representatives that is well positioned to influence policy and practice change to promote women'Äôs resilience, health and economic well-being at the local, national and regional levels. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Asociacion Programa Velasco,726890.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,El Salvador,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts,2022 +P23410,110026,Study on improving the pandemic policy responses to reduce adverse health effects on women workers in the export sector of Sri Lanka,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will study the relationship between government-sponsored economic schemes related to the COVID-19 pandemic for mitigating female job losses, success in retention and facilitating re-entry into the job market, and the unequal health and economic shock on female workers in the ready-made garment industry of Sri Lanka at the national level. The project will provide a broad picture of the economic performance of the industry and the pandemic'Äôs impact on employment and wages. It will analyze whether female workers were disproportionately affected by the pandemic and evaluate the effectiveness of the pandemic responses by the state and industry. It will identify the existing best practices to mitigate the adverse effects and suggest a fiscally feasible and gender-sensitive response mechanism for the future. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Institute of Policy Studies of Sri Lanka,731479.98,Human Populations,Asian,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Western Pacific,Unspecified,,,,Sri Lanka,,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +P23411,110027,Examining the socio-economic and health vulnerabilities of female bushmeat traders in the context of COVID-19 in Ghana,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks, and made unstable work relationships even more precarious, especially for women. Women in Ghana faced serious socioeconomic and health barriers prior to COVID-19, and there are clear indications that the pandemic has affected women more than men, especially those working in the informal sector. Women dominate the informal sector in Ghana, where they sell various commodities, including bushmeat. Even though bushmeat trading has long been a major livelihood activity for women, there is a lack of knowledge on the health hazards of the trade, including women'Äôs exposure to zoonotic diseases. This project will examine the interrelated factors that determine women'Äôs livelihood challenges and opportunities in the context of COVID-19, drawing on the case of women bushmeat traders in Ghana. The expected results include improved understanding of an insufficiently known livelihood activity for women, increased awareness of the issues among stakeholders and policymakers, and mobilizing efforts and resources to enhance the well-being of women participating in the bushmeat trade and the promotion of gender and health equity in Ghana generally. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,York University,666450,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2022 +P23412,110028,Impact of COVID-19 on livelihoods and HIV risk and vulnerability among women living in urban informal settlements in Uganda,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will study the impact of COVID-19 on employment (paid and unpaid), economic status, and HIV risk and vulnerability among women living in urban informal settlements in two major cities (Kampala and Mbale) in Uganda. It will also examine the strategies employed by women to cope with COVID-19-related work stresses that expose them to HIV risk and vulnerability. The evidence generated will support the development of a co-designed intervention package that encompasses inclusive, sustainable, and equitable gender-transformative solutions for COVID-19 recovery and future health emergencies. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,University of Waterloo,770000,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Women | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P23413,110029,Understanding the gendered impact of COVID-19 on young self-employed Nigerian women and co-producing solutions that foster better systems,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will study the impact of the COVID-19 pandemic and other disruptive events on the work and well-being of self-employed young women vis-√†-vis self-employed young men, using qualitative interviews, secondary data analysis and digital storytelling. The overall aim of this project is to support a suitable and contextually appropriate gender-transformative intervention to improve income security, mental, physical and social health, and social support systems for self-employed young women.'ÄØWorking with these women using policy analysis, focus group discussions and theory of change workshops, in addition to piloting and evaluating the intervention, will result in co-produced, actionable solutions to mitigate the effects of these disruptors on their work and well-being. The research will be primarily conducted in Oyo State in southwestern Nigeria.'ÄØ This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,University of Ibadan,758817.44,Human Populations,Black,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Nigeria,,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +P23414,110030,"Supporting health and economic well-being of women for an inclusive, sustainable and equitable post-COVID-19 recovery in Guinea","The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project aims to design and implement strategies that put women'Äôs health and economic well-being at the centre of COVID-19 recovery efforts and future emergency preparedness and response in Guinea. It will analyze the underlying causes of current policy inertia, co-create a gender-sensitive multi-sectoral policy framework and produce scientific publications and training curriculum for decision-makers. The project will ensure that institutional actors responsible for preparation, response and recovery from health emergencies proactively include gender-transformative and multi-sector measures in the design and implementation of health and economic policies. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada. 'ÄÉ",,,Université Gamal Abdel Nasser de Conakry,770000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Guinea,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2022 +P23415,110031,"Women in health and their economic, equity and livelihood statuses during emergency preparedness and response (WHEELER)","The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. In Kenya, the face of the pandemic health workforce response was predominantly female. A majority of workers experienced anxieties because of limited disease knowledge, limited access to protective equipment, increased COVID-19 disease exposure and infection, and a surge in domestic household responsibilities, including unpaid labour. Yet the socio-economic and health impacts of COVID-19 on the paid and unpaid female health workforce remains neglected. This project will study the gender equality and health equity gaps experienced by the female health workforce (paid and unpaid) in Kenya during the pandemic and how these experiences have impacted their physical and mental health, wellbeing, socio-economic status and livelihoods. It aims to improve understanding of the root cultural, structural, socio-economic and political factors that perpetuate gender inequities in the paid and unpaid health sector. These findings will inform the development of gender-sensitive and transformative health systems that can withstand future emergencies in Kenya. The project will also build local capacity in research, policy development and implementation, and ongoing professional development. This project is funded under the Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Aga Khan University-Kenya,755755,Human Populations,Black,Adults (18 and older),Unspecified,Women,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,Gender,,,Kenya,,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Economic impacts | Other secondary impacts | Health workforce,2022 +P23416,110032,Women recyclers' work and health in the context of COVID-19 in Ecuador,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. This project will assess the health conditions, policy factors, productive and reproductive work affecting women waste pickers in the context of COVID-19 in three cities of Ecuador: Cuenca, Portoviejo and Lago Agrio. The project team, in partnership with local organizations and decision-makers, will co-design and implement intersectoral interventions and gender-transformative strategies based on an inclusive, eco-friendly approach that addresses women waste pickers'Äô health and work conditions. Expected results include an in-depth understanding of labour (productive and reproductive work) and health conditions of a sample of 300 women waste pickers in the context of COVID-19; changes in women waste pickers'Äô labour practices (such as improved urban routes and transportation); and interventions that improve their occupational health conditions. There will also be a focus on strengthening the organizational practices and governance of the national network of waste recyclers; enhancing the capacities of the multi-institutional project team on equity, diversity and inclusion best practices; and involving strategic stakeholders and key decision-makers in the formulation of public policies to improve the living conditions of women waste pickers. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global, action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,Universidad de Cuenca,758220.08,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,Gender,,,Ecuador,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P23417,110045,Sexual and reproductive health of female sex workers in the post-COVID-19 era in Argentina,"The COVID-19 pandemic and efforts to control it have threatened livelihoods, introduced new workplace risks and made unstable work relationships even more precarious, especially for women. Female sex workers have been severely impacted by the pandemic and are one of the most marginalized and criminalized populations in Argentina. This project will analyze their sexual and reproductive health and the coverage of their income protection policies. It will involve the two main female sex workers'Äô national organizations and the local government of the City of Buenos Aires. The intention is to design and assess the feasibility of a comprehensive sexual and reproductive health prevention and care package; estimate the fiscal cost to close the existing income protection policy gaps; and translate the results and reach multisector policymakers at the local and national levels to improve prevention and healthcare and income protection policy coverage in the post-COVID era and for future health emergencies in Argentina. This project is funded under Women'Äôs health and economic empowerment for a COVID-19 Recovery that is Inclusive, Sustainable and Equitable (Women RISE), an initiative of IDRC, the Canadian Institutes of Health Research, and the Social Sciences and Humanities Research Council. Its aim is to support global action-oriented, gender-transformative research by teams of researchers from low- and middle-income countries and Canada.",,,University Health Network/Réseau universitaire de santé,742435.64,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sex workers | Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2022 +P23419,110056,Characterizing transmission dynamics and evaluating medical countermeasures to inform the clinical and public health response to monkeypox,"Outbreaks of monkeypox in Nigeria since 2017 and the 2022 global emergence of monkeypox in previously non-endemic regions, such as Canada, point to a need to characterize and compare the transmission dynamics in endemic and non-endemic regions. A critical aspect of the global outbreak has been transmissions in the context of sexual networks of gay, bisexual and other men who have sex with men (GBM). This project aims to characterize and compare monkeypox transmission dynamics across two diverse epidemic contexts; evaluate the role of antivirals in the treatment of human monkeypox (clinical trial); and evaluate the role of vaccination in the prevention of human monkeypox (real-world effectiveness). IDRC funds will only go to the African co-lead in Nigeria. Research methodology for the Nigeria work will include a mix of a prospective cohort study of suspected Monkeypox cases in two cities in Nigeria; surveillance study of subclinical infection among GBM; and formative research on trial readiness and vaccine acceptability in Nigeria. Comparative research in Canada (and internationally) will be funded through CIHR funds. A global research consortium will be carrying out this research and the Nigerian principal applicant is the Nigerian Institute of Medical Research. Results include rapid evidence on the transmission dynamics of monkeypox in the endemic and non-endemic regions to guide urgent policy decisions, clinical and public health program implementation surrounding medical and other countermeasures. The collective research infrastructure and multidirectional capacity building will provide a foundation to further expand and pivot to emergent monkeypox research questions as the epidemic re-shapes and unfolds over the next two years in Canada, Nigeria, and globally across diverse epidemic contexts.",,,Nigerian Institute of Medical Research,730000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Clinical,Unspecified | Not applicable,Poxviridae,,,,,,,,,Mpox,International Development Research Centre (IDRC),Canada,Americas,Africa,Unspecified,,"Epidemiological studies | Policies for public health, disease control & community resilience",Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Evaluation of elimination strategy implementation in different contexts.,Nigeria,,"Epidemiological studies | Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Disease transmission dynamics | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2022 +P23421,110095,"Fostering inclusive science, technology and innovation systems in Central America through strengthening capacities on open science","According to the 2021 Global Sustainable Development Report, strong science, technology and innovation (STI) systems are foundational to inclusive development and to restarting progress on the SDGs, especially following the COVID-19 pandemic. However, in most countries in Latin America and the Caribbean (LAC) investments in public research and development have stalled or decreased since the start of the pandemic. A second challenge is that existing funds are rarely deployed towards long-term investments in regional collaboration through research and capacity strengthening of STI systems, particularly in Central America and the Caribbean. Third, establishing strong national science structures in LAC, including science granting councils (SGCs), has been hindered by budget shortfalls, high civil-service turnover, public distrust in science, and political instability. Lastly, while SGCs in the region recognize the gender imbalances that remain in key fields at various levels, capacity gaps continue to hinder the formulation of policies that support gender inclusive STI agendas, placing women and excluded groups at the forefront of leading and benefiting from robust science systems. This project, selected through an open competitive call, is a significant investment by IDRC aimed to support more inclusive STI systems in Central America by strengthening the capacities of regional science bodies, particularly SGCs, to implement open science policies and practices within their agendas and to support regional coordination towards high quality research and innovation. To achieve this objective, selected partners will do a cross-regional analysis of open science policies, identify best practices for the Central American context, bring together key STI stakeholders across sectors to jointly develop a regional policy on open science and mobilize the development of more sustainable collaboration mechanisms, and sustainably strengthen capacities of key STI actors to implement the agreed upon policy. Countries eligible for support include Belize, Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua and Panama. The project will be led by a consortium formed by Secretar√≠a Nacional de Ciencia, Tecnolog√≠a e Innovaci√≥n, Fundaci√≥n Ciudad del Saber, Consejo Superior Universitario Centroamericano, Sistema de la Integraci√≥n Centroamericana, and Comisi√≥n para el Desarrollo Cient√≠fico y Tecnol√≥gico de Centroam√©rica y Panam√°. 'ÄÉ",,,"Panama. Secretaría Nacional de Ciencia, Tecnología e Innovación",1094854,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Panama,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P23422,110117,"Solidarity Against Tokomeza Ebola 'Äì Safety, immunogenicity and efficacy of Sudan Ebola virus vaccines in Uganda","Uganda reported its first confirmed case of Ebola in over a decade on September 20, 2022, with no known treatment or vaccine for the Sudan strain that was responsible for the outbreak. Within 79 days, the World Health Organization and the Uganda Ministry of Health designed a ring vaccination clinical trial, mobilized a trial team and had over 5,000 doses of three candidate vaccines shipped to Uganda. On January 11, 2023, Uganda declared the end of the outbreak that had affected nine districts and caused a total of 164 cases and 77 deaths. While the response to the Ebola outbreak in Uganda was relatively fast, the disease outbreak research community and global health community recognize that in order to save lives, more could be done between disease outbreaks so that at-risk countries can respond more quickly, narrowing the lead time between the declaration of an outbreak and a country'Äôs readiness to start a clinical trial. Through this project the World Health Organization will integrate research and development into the initial response to outbreaks to ensure access to life-saving medical countermeasures in Uganda and other at-risk countries (Rwanda and Tanzania). Specifically, the project will evaluate the safety and immunogenicity study of three candidate vaccines using a multistage and multiple arm randomized double-blind placebo controlled clinical trial. These candidate vaccines were recommended for clinical studies by an independent vaccine prioritization committee of experts convened by the World Health Organization in November 2022. The study is expected to last up to 24 months and enrol approximately 6,000 participants. Additionally, the project seeks to build national clinical trial capabilities to respond to future outbreaks and to strengthen local and global capabilities for clinical research on vaccines for priority diseases. The project will be led by the World Health Organization and the Uganda Ministry of Health. It is supported by the Government of Canada through a joint investment of IDRC, the Canadian Institutes of Health Research and the Public Health Agency of Canada.",,,World Health Organization/Organisation mondiale de la santé/Organización Mundial de la Salud,3536996,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Filoviridae,,,,,,,,,Ebola virus disease,International Development Research Centre (IDRC),Canada,Americas,Europe,Unspecified,,,,Switzerland,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase),2023 +P23423,110149,Market authorization of the Peste des Petits Ruminants-Rift Valley Fever (PPR-RVF) combination vaccine in West and East Africa,"Livestock vaccines have an important role to play in protecting the health and well-being of animals as well as the human populations that rely on them for food and other products. However, many vaccines that have a significant impact are not widely adopted by small-scale livestock farmers in Africa, due to various factors such as lack of awareness, limited access and affordability. As a result, there is a need to explore innovative approaches to promote the use of existing vaccines and improve access to new and improved vaccines, particularly in low- and middle-income countries. The Livestock Vaccine Innovation Fund (LVIF) is a program that supports research to test novel approaches to scaling the demand, access and use of new or improved livestock vaccines. A previous project supported by LVIF resulted in the development of combined vaccines for large and small ruminants, including one for Rift Valley Fever (RVF), a disease affecting both animals and humans. The project resulted in the successful development of a combined RVF and Peste des Petits Ruminants (PPR) vaccine, which is registered in Morocco as Ovivax PPR+RVF. The current initiative aims to support field trials and registration of the Ovivax PPR+RVF vaccine in West and East African countries to further scale up its use. These trials will evaluate the safety, efficacy and immunogenicity (ability to produce an immune response) of the Ovivax PPR+RVF vaccine.",,,MCI Sante Animal,313316,Animals | Human Populations | Not applicable,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,"Clinical Trial, Veterinary",Bunyaviridae,,,,,,,,,Rift Valley Fever | Other,International Development Research Centre (IDRC),Canada,Americas,Eastern Mediterranean,Unspecified,,,,Morocco,,"Animal and environmental research and research on diseases vectors | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Clinical trial (unspecified trial phase) | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2023 +P23424,110208,The evolution of host-flavivirus interactions and their impact on viral pathogenesis and host response,"The ability of viruses to rapidly change is key to their success, allowing them to quickly adapt to new hosts as well as to replicate in extremely different environments. Understanding how viruses evolve to efficiently infect in new environments as well as revealing the barriers and limitations to this capacity are important to predicting emerging threats and to designing novel therapeutic interventions. This project focuses on the flaviviruses, a group that includes many human pathogens such as the dengue virus and the zika virus. These viruses infect millions of humans across the world every year, causing widespread mortality and morbidity, especially in developing countries. These pathogens are transmitted to humans from ticks and insects, and they are thus able to replicate in two extremely different host environments. The molecular mechanisms that affect the potential of flaviviruses to shift hosts and become a new human pathogen remain poorly understood. An important factor contributing to virus replication within a given host is the virus'Äô capacity to inhibit intracellular host defences by direct interactions with the host proteins involved in innate immune responses. A non-structural protein 5 (NS5) is common to all flaviviruses and is believed to be important for modulating host innate immune response. This project aims to investigate the hypothesis that NS5 diversity among flaviviruses is central to host modulation and virus spread. The project will create a comprehensive map of its interactions with human and mosquito proteins and study how host-flavivirus interactions impact on host immune processes. This project was selected for funding during the second research competition of the Joint Canada-Israel Health Research Program 'Äì Phase II (Communicable Diseases). The program is a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation and the Azrieli Foundation.",,,Fundación Instituto Leloir,730000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,International Development Research Centre (IDRC),Canada,Americas,Americas,Unspecified,,,,Argentina,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P23425,101073982,MOBILISE: A novel and green mobile One Health laboratory for (re-)emerging infectious disease outbreaks,"Mobile laboratories are becoming increasingly important for quick response to epidemic outbreaks in remote areas. Due to climate change and rising temperatures, emerging arboviruses (Crimean-Congo haemorrhagic fever virus, West Nile Virus, Rift Valley fever, Dengue fever) are finding their way into Europe through arthropod vectors (mosquitoes, ticks), and are becoming a major public health concern. Optimally monitoring zoonotic outbreaks requires a ""One Health"" approach, in which not only human, but also animal and environmental samples are analysed, as close as possible to the vectors' habitat. Also returning travellers might carry haemorrhagic Ebola/Marburg virus or respiratory pathogens such as SARS-CoV-2. A survey of existing European mobile laboratory capacity revealed several shortcomings: of 193 labs, 66% were civilian, 88% were exclusively for human diagnostics, with 11% having an accredited quality management system, and only 3% had the highest bio-safety level BSL-4 needed for (haemorrhagic) arbovirus handling. MOBILISE aims to close this diagnostic gap, by developing a novel, quality-assured, mobile One Health laboratory solution, to provide BSL-4 capacity to many European countries. It will receive human/animal/environmental samples for molecular diagnostics, serology, microbiology, and host a whole genome sequencing platform for pathogen discovery and epidemiological analysis. We will further develop novel rapid diagnostic tests for BSL-3/4 pathogens, and produce results in machine-readable form. A novel AI-based ""Emergency Operating Centre and Decision Support System"" software will assist end-users in coordinating MOBILISE fleets across Europe and manage outbreaks in real-time. Hosted on an electric/hybrid truck platform, and using solar and wind-energy, it will also reduce CO2 emissions in compliance with the European Green Deal. The lab will be field-tested to TRL-7 by National agencies and first-responders in Austria, Romania, Greece and Africa.",,2025,BERNHARD-NOCHT-INSTITUT FUER TROPENMEDIZIN,3879894.27,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23426,101005077,Corona Accelerated R&D in Europe,"The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has emerged as the largest global health threat to humanity in this century. As of March 28th 2020, more than 664,000 patients were diagnosed with Coronavirus Disease 2019 (COVID-19) and 30,000 deaths reported across 199 countries. The wide spectrum of clinical symptoms, disease severity in high risk individuals, transmission efficiency and high mortality, raises an immediate need for vaccines or therapeutics. Given that the viral variant is new in the human population and emerged less than 4 months ago, there is no vaccine or approved therapies. The CARE consortium is a coalition of 36 globally renowned academic institutions, pharmaceutical companies and non-profit research organizations who have committed to rapidly and efficiently address this emergent health threat, and the main objectives are: the development of therapeutics (i) to provide an emergency response towards the current COVID-19 pandemic by drug repositioning and (ii) to address the current and/or future coronavirus outbreaks by broad-spectrum small-molecule drug discovery and/or virus-neutralizing antibody discovery. To achieve this, a collection of repurposed drugs, focused libraries and small molecule libraries will be screened against SARS-CoV-2, other emerging SARS-CoV-2 clades and related coronavirus genera in phenotypic or target-based assays. ADME, PK/PD, potency and safety of these therapeutic candidates will be assessed in vitro and in animal models. Virus-neutralizing monoclonal antibodies will be generated and further characterized. Immune markers will be identified contributing to the host immune responses to SARS-CoV-2 infections, and the correlation with clinical and virological outcomes will be determined. Finally, lead candidates will be advanced into Phase1 and Phase 2 clinical trials in humans. With this reactive response, the CARE consortium is dedicated to win the fight against coronavirus.",,2025,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,39849512.74,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies | Phase 1 clinical trial | Phase 2 clinical trial | Prophylactic use of treatments,2020 +P23427,101005026,Modern approaches for developing antivirals against SARS-CoV 2,"The SARS-CoV-2 pandemic has become an unprecedented burden to public health, our civil societies and the global economy. To provide frontline therapies for COVID-19 and future corona virus outbreaks requires a concerted effort of different disciplines, technologies, high security labs, and rapid translation of scientific findings to highly innovative and 'Äúhungry'Äù SME partners. For the MAD-CoV-2 project we have assembled a multidisciplinary team of world-leading researchers and innovative industry partners to unlock the Achille'Äôs heels of the virus infections in host cells and rapidly translate such knowledge into disruptive new medicines and public health measures. Our team members have been on the ground of the first SARS and Ebola outbreaks, head containment facilities to study highly infectious viruses, are world-leading in engineering human tissues, developed breakthrough technologies that allow us to find host factors for viral infections at unmatched speed and resolution, and discovered ACE2 and made the first in vivo link between ACE2, SARS, and lung injury, leading to rational drug development which is imminent to be tested in European COVID-19 patients. ACE2 is also the key receptor for SARS-CoV-2 Spike protein and has got centre stage for novel therapies and a fundamental understanding of COVID-19. The aims of MAD-CoV-2 are 1. to engineer human tissues to test novel therapies and vaccines; 2. to provide critical evidence on the role of clinical grade ACE2 in viral replication and COVID-19 pathogenesis; 3. to perform high-throughput screens to genetically map, at a single amino acid resolution, essential host factor that are critical for SARS-CoV-2 replication; and 4. to rapidly translate this knowledge into novel therapies to fight the current and, importantly, future corona virus outbreaks. Our data and unique tissue reagents will be made available to the entire community for drug testing and development, supporting all other efforts.",,2024,STATENS VETERINAERMEDICINSKA ANSTALT,4424609.42,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies | Pre-clinical studies",2020 +P23428,101016038,PORTABLE AND FAST SURFACE PLASMON RESONANCE POINT-OF-CARE TEST FOR COVID-19,"The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has led to more than 7.031.249 cases and 403.112 deaths globally as of June 8, 2020. Although most infections are self-limited, about 15% of infected adults develop severe pneumonia that requires treatment with supplemental oxygen and an additional 5% progress to critical illness with hypoxaemic respiratory failure, acute respiratory distress syndrome, and multiorgan failure that necessitates ventilatory support, often for several weeks. Worldwide, infections and death from SAR-CoV-2 continue during June with more than 110.000 new cases every day despite lockdown in Europe and oversees. What started as a temporary sanitary issue, has morphed into a more permanent and long-lasting pan epidemic outbreak. One efficient manner to limit COVID-19 spreading and an adequate mean of better managing the COVID-19 outbreak is through unrestrained availability of fast, efficient, accurate and cost-effective point-of-care tests (POCT). Here we propose C-POCT-S, a rapid (<30 min), sensitive (200 vps/mL), selective (SARS-CoV-2), and inexpensive ( < 20 Euros) solution to address this medical need. C-POCT-S is based on a combination of several technologies such as the use of COVID-19 specific nanobodies (VHH), magnetic nanoparticles with high magnetic strength and a VHH modified interfaces, all integrated in a a hand-held surface plasmon resonance (SPR) based POC test (C-POCT-S) for the screening of the presence/absence of the SARS-CoV-2 virus in nasal and salvia samples. The aim of this project is to complete product optimization, performance validation in a clinical setting and manufacturing quality control for C-POCT-S and completion of its technical file, to enable declaration of conformity and affixing of CE mark.",,2022,UNIVERSITE DE LILLE,2794828.8,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23429,101005075,"Evaluation of a production ready portable, Point-of-Need Platform (instrument and reagents), direct from nasal swab test for the molecular diagnostic detection of COVID-19 infection.","This project focuses on rapid (40min), simple, Point-of-Need COVID-19 testing, e.g. surgery/home (via first responders)/transit points of entry. BG Research (BGR) has developed direct from crude sample detection of viral pathogens 'Äì the QuRapID-XF technology, removing requirement for nucleic acid extraction, expert users or a laboratory; results delivered while you wait. Tests utilise the Gold Standard polymerase chain technology as current clinical reference tests, but using our novel reagent, directly breaking open the virus and a single enzyme system that is resistant to the inhibitory compounds found in crude biological samples. Objectives: 1. Develop a lyophilised assay for direct detection of SARS-CoV-2 from nasal swab samples. 1. Production scaling of a portable instrument for performing the test at Point-of-Need. 2. Demonstration of a pipeline for rapidly deploying new assays in response to future outbreaks and detection from a wider range of sample types. 3. Validation of the assay at 3 independent sites using clinical samples, generating data sets for regulatory approval. Achieving the objectives: BGR has pre-production portable systems in testing for the in-field detection of veterinary diseases from animal nasal swabs. This project will bring scaled production of the product forward by minimally 3 months together with a validated lyophilised SARS-CoV-2 assay. The team has proven experience in diagnostics design and development and will have access to clinical patient samples from Italy and France, generating quantified standards and performance evaluation data that BG Research will document under its ISO13485 quality standard and generate data for MDSAP and hence EUA regulatory approval. Relevance to Work P: The IMI2 call is seeking innovative diagnostics to have impact in combating the current Coronavirus outbreak and this proposal to provide rapid and simplified differential diagnostics at the point of need, is directly aligned with the scope.",,2022,UNIVERSITE D'AIX MARSEILLE,941364,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23430,101136281,PROTECTION FROM VIRUSES WITH EPIDEMIC AND PANDEMIC DISEASE OUTBREAK POTENTIAL THROUGH DEVELOPMENT AND CLINICAL TESTING OF A NOVEL CAPSID VIRUS LIKE PARTICLE (CVLP) VACCINE,"The enormous health and economic impacts of epidemics and pandemics has become one of the defining public policy and health issues in Europe and throughout the world. A new urgency is required to understand, rapidly respond to, and vaccinate against viruses with epidemic and pandemic potential. The major challenge for the modern vaccines is the induction of long-term protective immunity, as clearly demonstrated by fast waning of protection for current COVID-19 vaccines. VICI-DISEASE is an ambitious project which combines existing cutting-edge expertise in a tried and tested consortium, with new advances in this critical field. The consortium'Äôs main objective is to develop a vaccine candidate portfolio and perform a clinical proof-of-concept study, to enable stocks of vaccine candidates ready for further development (Phase 2&3) in case of pandemic outbreaks. The primary candidate will be Nipah virus (NiV), a high-mortality viral disease with no vaccines or treatments. Our vaccine is based on NiV G protein displayed on capsid Virus Like Particle (cVLP), enabled by adapting template processes from our recent COVID-19 vaccine (currently in Phase 3), and expected to provide best-in-class longevity as shown for COVID-19. The VICI-DISEASE consortium'Äôs objective is to develop and perform a clinical proof-of-concept study for 'Ä¢ a highly effective (>90% protection), 'Ä¢ long-term protective (>2 years), 'Ä¢ NiV virus cVLP vaccine, 'Ä¢ by adapting template processes established for our COVID-19 vaccine (currently in Phase 3), 'Ä¢ within 48 months in a Phase 1/2a clinical study, 'Ä¢ to help protect medical workers and the public from future NiV and Hendra virus outbreaks, 'Ä¢ and establish a pipeline of novel filovirus vaccines through pre-clinical proof-of-concept studies. We address the call topic by improving pandemic preparedness and response through development of a NiV vaccine to Ph1/2 and two filovirus vaccines to pre-clinical proof-of-concept.",,2027,KOBENHAVNS UNIVERSITET,17336442.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Denmark,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2023 +P23431,101003651,Monoclonal Antibodies against 2019-New Coronavirus,"Lessons learned from, and intervention efforts against SARS coronavirus (CoV), MERS-CoV and other emerging viruses provide invaluable information to accelerate the coordinated response against 2019 novel (2019 -n)CoV and the rapid development and manufacture of new diagnostic, prophylactic and therapeutic intervention strategies. A -promising approach to both patient management of emerging viral infections and to better preparedness and response to emerging epidemics is the use of monoclonal antibodies. MANCO aims at contributing to the rapid international response against 2019-nCoV, through preclinical and clinical evaluation of monoclonal antibodies against 2019-nCoV. MANCO will build on and leverage outstanding results from ongoing IMI-funded project #115760 ZAPI, including recently-discovered broadly cross-reactive H2L2 monoclonal antibodies against betacoronaviruses and an established pipeline for rapid identification of specific H2L2 monoclonal antibodies against 2019-nCoV; antibodies that will be selected to proceed to GMP manufacturing in high-yield CHO cell-lines. This project furthermore builds on ZAPI consortium'Äôs experience and expertise for the development and establishment of relevant animal models, to ensure preclinical efficacy and safety, including absence of antibody-dependent enhancement, an issue seen to occur in some immunization studies against feline and SARS CoVs. Based on the generated preclinical data, MANCO will advance one lead (prophylactic and/or therapeutic) monoclonal antibody into a Phase I clinical trial that can be completed within two years of the start of the project, by leveraging clinical expertise, infrastructure and network currently in place for ongoing CEPI-funded projects on candidate vaccines against MERS-CoV (#INID1801) and Rift Valley Fever virus (#INLA1901), and H2020-funded projects on improved vaccines targeting the elderly (ISOLDA #848166) and on universal influenza vaccines, including in LMICs (ENDFLU #874650).",,2023,ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM,3338039.1,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23432,101076648,Outlining the Role of IgA in Memory Instruction,"Several times in human history, we faced sudden outbreaks of respiratory viruses that rapidly spread over the world before we could design broadly protective vaccines. Such was the case of the H1N1 influenza virus that killed 50 million people during the 1918 Spanish flu and SARS-CoV-2 that led to at least 5 million deaths during the current COVID-19 pandemics. Influenza and SARS-CoV-2 elicit robust humoral immune responses, including production of virus-specific antibodies of the IgM, IgG, and IgA types. In particular, IgA plays a crucial role in protecting lung mucosal surfaces by neutralizing respiratory viruses and impeding their attachment to epithelial cells. Despite its protective role, current vaccines against influenza and SARS-CoV-2 fail to produce significant levels of IgA in the respiratory tract. Then, a deeper understanding of the biology of IgA+ cells during respiratory infection is of utmost interest. ORIgAMI is based on recent unexpected findings from my team showing that germinal center B cells expressing IgA are mostly recruited towards the long-lived plasma cell compartment rather than to the memory B cell one upon influenza infection. In this frame, we will determine if the IgA BCR biases cell fate by: 1-Imprinting germinal center B cells with specific transcriptional/epigenetic programs. 2-Favoring antigen extraction and recruitment of T cell help within germinal centers. 3-Enhancing downstream B cell signalling pathways. To to this end, we will use influenza H1N1 virus as respiratory infection model combined with a series of complementary innovative tools and methodologies: de novo-generated transgenic mice, single-cell RNA/ATAC-seq, 3D imaging, DNA-based force sensors, phospho- and imaging- flow cytometry, and mass-spectrometry. A deep understanding of the biology of IgA+ B cells during respiratory viral infection is of fundamental interest and may provide clues towards the design of future vaccination approaches against air-borne pathogens.",,2028,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,2212972.92,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,H1,H1N1,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P23433,101016083,Market Release of a Portable Device for COVID-19 at the Point-of-Care; a Global Diagnostics Approach,"The current pandemic of the coronavirus, reported first on 31st December 2019 in China, has produced a global alert of unprecedented nature. From the beginning, immediate actions have been put in place by all relevant stakeholders, i.e., local health departments, governments, pharmaceutical companies, global organisations etc., to address the problem as quickly as possible and control the spread of the disease. Large scale testing of symptomatic and asymptomatic patients/citizens has been one of the most effective measures taken by several countries, combined with isolation and tracking. Today, after six months from the outbreak, the deaths continue to rise with over 200 affected countries. Fear of a new wave of the pandemic together with the ongoing cases worldwide make the need for developing rapid and accurate diagnostic tools for COVID-19 a global priority, as declared by the WHO. The current consortium aims to join forces in the battle against the coronavirus by producing mature and robust solutions with immediate impact. The proposal is built around the implementation of an existing and patented device and methodology based on isothermal LAMP amplification and real time quantitative colorimetric detection. This mature methodology, currently of a technology readiness level of 7, has already been proven to be able to detect SARS-CoV-2 in patients'Äô samples with 97.4% sensitivity and 100% specificity. The main objectives of this proposal are thus the immediate deployment of the device following clinical validation and fast track certification. Arrangements for the large-scale production of the device and reagents will take place in parallel, followed by the provision of a full medical certification for COVID-19 and flu detection directly in crude samples and at the point-of-care. Global uptake of the two certified products together with global sharing of the project results are important deliverables of the proposal for the current and future epidemics.",,2022,IDRYMA TECHNOLOGIAS KAI EREVNAS,2790307.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Greece,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23434,101016072,A diagnostic test to improve surveillance and care of COVID-19 patients,"Coronavirus disease 2019 (COVID-19) caused by infection with SARS coronavirus 2 (SARS-CoV-2) has reached pandemic proportions with more than 7 million people infected and 0.4 million people killed worldwide. Death rates are accentuated by cardiovascular comorbidities and arrhythmias leading to unexpected major cardiovascular events. Being able to identify COVID-19 patients at risk of developing cardiovascular events leading to death would allow improving surveillance and care. Currently, there is no accurate method to predict outcome of COVID-19 patients. COVIRNA is a patient-centered Innovation Action aiming to satisfy this urgent and unmet need. COVIRNA will complete and deploy a prognostic system based on cardiovascular biomarkers of COVID-19 clinical outcomes combined with digital tools and artificial intelligence analytics (i.e. prediction model). Complementary expertise of 15 EU partners from the healthcare sector, academia, association and industry will allow conducting a large retrospective study on existing cohorts of COVID-19 patients. By upscaling the already validated and patented research use only FIMICS panel of cardiac-enriched long noncoding RNA biomarkers into an in-vitro diagnostic test (COVIRNA) adapted to COVID-19 patients, the project will quickly deliver a minimally-invasive, simple yet robust and affordable prognosis tool that can be used in the context of the current COVID-19 crisis as well as in further major health issues. By tackling the cardiovascular complications in COVID-19, known to contribute significantly to mortality, the project outputs are expected to have a major impact on the pandemic outcomes. The COVIRNA test will be CE-marked and prepared for commercialization, allowing to risk stratify patients, adapt therapies and to inform drug design.",,2023,LUXEMBOURG INSTITUTE OF HEALTH,4533161.49,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Luxembourg,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P23435,961112,Revolutionary vaccines to prevent pandemic and seasonal outbreaks of respiratory viral infections: The best-in-class UNIVERSAL multi-season influenza vaccine,"While an ongoing pandemic outbreak of coronavirus (COVID-19) is having enormous impact on global societies, a quest for effective vaccination becomes of unprecedented importance to save lives and economies globally. Symptomatic flu, another respiratory RNA viral infection, affects ~10% of global population every year and leads to regular pandemic outbreaks. Existing prophylactic vaccination requires updates each flu season or pandemic outbreak, and has a strikingly limited efficacy (40% on average, as low as 9% in elderly). This is mainly due to a rapid mutation rate of surface viral proteins that are targeted by the current vaccines. Governments, institutions and vaccine community urgently seek for a universal flu vaccine that would provide a multi-season protection against all seasonal and emerging pandemic viral strains. OSIVAX, a French clinical stage innovative biotech, strives to develop vaccines able to prevent respiratory viral infections across multiple seasons and outbreak. OSIVAX has developed OVX836, a best-in-class, game-changing universal flu vaccine candidate. OVX836 is based on oligoDOM¬Æ, a proprietary immune-boosting technology that triggers powerful, targeted and durable immune responses involving activation of specific immune response killing infected cells. OVX836 circumvents the need for annual vaccination updates by targeting an intraviral protein that is highly conserved across all influenza strains. OVX836 has a potential to disrupt the flu vaccine market currently dominated by single-season vaccines. The revolutionary universal flu vaccine is predicted to have a blockbuster potential (>'Ǩ2.5 billion). OSIVAX'Äôs experienced team aims to get OVX836 ready for the clinical proof-of-efficacy milestone (Phase IIb) that will position the company for >'Ǩ500M licensing deal with a big pharma in 2024. At the moment, OSIVAX leverages this revolutionary clinical-stage technology to initiate the development of a universal vaccine against corona",,2022,OSIVAX SAS,2682622.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Vaccines research, development and implementation",Phase 2 clinical trial,2020 +P23436,959436,"COVID-19 pandemic: An innovative, safe and effective bio-decontamination technology for non-toxic removal of biological agents, including coronavirus","Infectious diseases, such as COVID-19, plague, Ebola, SARS and flu, caused by biological agents, are among the most serious and least predicted threats facing the global community. As we currently experience with the COVID-19 pandemic, bioagents can cause enormous societal and economic damage. Unlike, in the case of chemical, radiological or nuclear incidents, like e.g. in Chernobyl where people could not do much to stop the spread across Europe, in the case of the COVID-19 outbreak, public has a real power to reduce the impact by social distancing, respiratory etiquette, hand hygiene and decontamination in an attempt to flatten the curve. Current decontamination solutions are suitable for hard surfaces but based on chemicals that cannot be used repeatedly on skin because they are harmful to humans, lead to health complications (hormonal imbalance, allergic reaction and dryness etc.) and damage the environment. There has been a lack of innovation in human-decontamination technologies over the decades and there is a clear need for technologies that can deliver safe, effective and immediate decontamination of human skin. The technological innovation of ABwipe offers a paradigm shift in decontamination. ABwipe is a unique product, inspired by nature and exploiting the mechanism of pathogen binding. It is made up of a matrix material (cellulose fibres) with attached carbohydrate-protein binders, carefully selected with strong affinities for biothreat agents, including pandemic agents such as influenza and coronavirus. ABwipe not only decontaminates but also captures and contains biological agents. This is a significant capability that reduces the impact, impedes the spread of the infection and allows forensics and diagnostics to identify harmful agents. It is an effective, safer, better and fit for purpose solution for potentially devastating bioagent threat to the society, saving lives, restoring the health of victims and returning contaminated areas to a safe state",,2023,AQUILA BIOSCIENCE LIMITED,2290343.42,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P23437,101046314,ENDING COVID 19 VARIANTS OF CONCERN THROUGH COHORT STUDIES: END-VOC,"The END-VOC consortium will support the European and global response to the COVID-19 pandemic and Variants of Concern (VOC) through well characterised cohorts and linked with existing European and international initiatives. END-VOC consists of 19 partners in Europe (UK, Spain, Italy, Germany, Netherlands, Norway, Italy), South America (Brazil and Peru), Africa (Mozambique, South Africa, Nigeria and 13 ANTICOV African countries), Middle East (Palestine) and Asia (India, Pakistan, Philippines) with a focus on countries affected by VOCs and VOIs. We will elucidate the global circulation of the current and emerging SARS-CoV-2 VOCs and their characteristics, including transmissibility, pathogenicity and propensity to cause reinfection, to support best control strategies and the development of diagnostics; evaluate the impact of VOCs on the effectiveness of different vaccines and vaccination strategies; and assess the implications of VOCs on the choice of optimal treatment options. END-VOC will also investigate how VOCs alter long-term post-infection sequelae and where new VOCs emerge within hosts using our clinical cohorts. We will inform future preparedness and response working closely with international and national public health organisations and existing cohort consortia. Specific beyond state-of-the-art components of END-VOC include the use of novel phylogenetic prediction tools and mathematical modelling; generation of powerful cohorts through sentinel surveillance in low and middle income settings and cohorts of travellers to increase our global reach; use of novel predictive modelling of clinical outcomes by VOC and comorbidity/treatment and evaluation of differences in natural and vaccine immunity by VOC; antiviral screening models within cohorts and an artificial intelligence driven tool for the prediction of long COVID.",,2025,UNIVERSITY COLLEGE LONDON,10496969.7,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Diagnostics | Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics | Disease surveillance & mapping | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity",2022 +P23438,101065094,The tRNA epitranscriptome: a novel player in viral infections,"Recent evidence indicates that codon usage bias regulates gene expression, as synonymous codons are not decoded with the same efficiency. Viruses are entirely dependent on the host translation machinery to express their proteins. Puzzlingly, the genomes of diverse viruses synthesize viral proteins at high levels, such as those of the emerging Chikungunya virus (CHIKV), dengue virus (DENV) and the pandemic SARS-CoV-2 are enriched in rare codons that should slow down their translation. How these viruses achieve this high protein expression remains a fundamental question in virology. In Juana D√≠ez's laboratory, recent findings have revealed an unprecedented interplay of the Chikungunya virus (CHIKV) with the host tRNA epitranscriptome. CHIKV adapts the host translational machinery toward viral codon usage by overexpressing a tRNA modification enzyme that favors translating a specific set of codons enriched in CHIKV RNA. The proposed project will combine cellular, and molecular biology approaches with -omics analyses to further develop this novel research area and explore its translatability. First, using SARS-CoV-2 as a model, we will study whether the observed CHIKV-induced codon-specific reprogramming of the host translation machinery represents a common mechanism to optimize viral protein expression. Second, we will characterize the tRNA modifying enzymes involved. Third, we will explore the antiviral therapeutic interest of the identified enzymes. Together, these findings will shed light on a novel layer of virus-host interaction and might provide a rationale to consider the regulation of the host tRNA epitranscriptome as a promising target for the development of broad-spectrum antivirals.",,2025,UNIVERSIDAD POMPEU FABRA,181844.3,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P23439,101003608,Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine,"Our aim is to perform pre-clinical and clinical evaluation of a potential Wuhan Coronavirus vaccine candidate. The vaccine will be based on Virus-Like Particle (VLP) display of the SARS-CoV-2 Spike protein antigen. AdaptVac's VLP display technology has been shown to significantly improve vaccine immunogenicity, longevity and efficacy, for a wide range of viral and parasite diseases in pre-clinical studies (including flu and malaria). A unique feature of the technology is its two component approach. The VLP is generic to all vaccines, and produced at >1g/L yields using E.coli. The disease antigen is produced in any expression system, allowing the most challenging antigens to be successfully produced. The VLP and antigen is then simply mixed, and a spontaneous, irreversible, conjugation occurs under physiological conditions. This results in site-specific, directional , and high density display of the antigen on the VLP surface. The antigen will be produced using ExpreS2ion's Drosophila S2 insect cells (as trimetric full-length spike proteins). Furthermore, E.coli and baculovirus will be tested for Spike protein variants. The vaccine candidates will be tested pre-clinically using in vitro viral neutralisation assays and possibly animal challenge models as they become available at LUMC. ExpreS2ion will develop the production processes and transfer these for GMP manufacture of the VLP and vaccine antigen, outsourced, to IntraVacc (NL). Finally, a phase I/IIa study will be performed at EKUT, University of T√ºbingen, Germany. A surrogate marker of protection will be established by showing protection in animal models using passive transfer of patient sera, or by in vitro SARS-CoV-2 viral neutralisation. This project is focused on delivering a scalable vaccine, ready for testing in the field, which has been shown to be safe in humans and effective in in vitro or animal models.",,2022,KOBENHAVNS UNIVERSITET,2973890.6,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2020 +P23440,101003650,Antibody therapy against coronavirus (COVID-19),"ATAC aims at developing passive immunotherapy against COVID-19. Human antibodies will be obtained from blood of CoV-recovered donors from China and Italy with three independent approaches: polyclonal gamma-globulins, B cell monoclonals and phage libraries. Antibodies will be characterized by rapid experimental and computational work, optimized, produced and tested in consultation with EMA to ensure prompt embedding of regulatory aspects. The partners have outstanding experience in all aspects of the project, collaborated previously and worked on antibody therapy for diseases including SARS and MERS-CoV. Reagents and experienced personnel are already available ensuring quick and efficient progress, with initial deliverables within 3 months. Besides providing a lead human antibody candidate for therapy, ATAC will rapidly disseminate results to help respond to the current COVID-19 epidemic. Results of the 2 years project will also further our understanding of CoV neutralization, contributing to future vaccination and therapeutic strategies. The team includes the Karolinska Institutet (SE, Pan-Hammarstr√∂m and Hammarstr√∂m, coordinators), the Institute for Research in Biomedicine (CH, Varani and Robbiani); the Joint Research Centre- European Commission (BE, Calzolai); Technische Universit√§t Braunschweig (DE, Hust) and Policlinico San Matteo (IT, Baldanti). The partners'Äô outstanding expertise is attested by high impact publications on antibody treatment for emerging infectious diseases.",,2023,KAROLINSKA INSTITUTET,6098593.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23441,894449,Canonical and non-canonical secretory mechanisms of cytokines in bat and human cell cultures in response to coronavirus infection: a comparative study,"The majority of coronaviruses (CoV) originally emerged from bats including highly pathogenic SARS- and MERS-CoV. Bats evolved unique innate immune mechanisms that are likely responsible for the lack of immune pathology. One key process of the immune response is the secretion of cytokines, like interleukins (IL) and type I interferons (IFNs), however molecular details of cytokine secretions and their influence on the outcome of virus infections have not been studied in context of reservoir host species like bats. The aim of this research proposal is to determine the molecular mechanisms involved in the secretion of IL-1 and IFN in human and bat cells that could explain why bats have developed a tolerance against coronavirus infections. The training-through-research of the candidate will consist in analyzing the secretion of IFNs and IL-1 in cell culture supernatants of bat and human CoV-infected cells subjected to knockdowns of different molecules implicated in canonical or non-canonical secretory pathways, as well as activation and interactions between receptors of both secretory pathways. The multidisciplinary nature of the project is strong, involving a combination of well developed molecular biology, cell biology, and virology. This proposal includes both the transfer of knowledge to the host institution and the training of the candidate in new advanced techniques and transferable skills. The results will show in-depth mechanistic insights into bat cytokine secretion, which still has some gaps in its knowledge, and will serve as a promising platform for the development of new antiviral strategies to fight emerging zoonotic viruses, in line with the EU strategy listed Societal Changes of H2020 for the health, demographic change and wellbeing. The dissemination of the results to the scientific community will be done by publications in international open-access peer-reviewed journals, congresses, press releases and participation at science divulgation events.",,2023,CHARITE - UNIVERSITAETSMEDIZIN BERLIN,192111.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P23442,101057129,Respiratory Host-Pathogen Interaction,"Lower respiratory tract infections resulting from seasonal epidemics and pandemics are among the leading causes of death globally. There is a paucity of treatment options for viral respiratory pathogens and patient care remains largely supportive. This underscores a desperate need for identifying novel targets for prophylactic/treatment interventions and early prediction models of disease outcome to personalise treatment. The REACT consortium ? uniting high-level experts in virology, immunology, clinical medicine, epidemiology, and bioinformatics ? will assess genotypic, high-dimensional immunophenotypic, demographic and clinical data in the context of disease course to define host-pathogen interactions of viral respiratory tract infections, focusing on the predominating viruses i.e. influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In characterised, ethnically diverse clinical cohorts comprising patients with varying disease severities, we will genotype both virus and host, map deep immunological phenotypes spanning cellular, humoral and innate immunity, and characterise host responses in human nasal epithelial organoid models following viral infection. Novel bioinformatics approaches that include knowledge discovery and machine learning will be used to integrate and analyse multidisciplinary datasets to assess the individual and combined impact of factors on disease phenotype. Information on the deep characterisation of the dynamics of the immune responses to the chosen viruses and identified factors critical for viral control and immune protection will be made available on a dedicated project website to clinicians, researchers, health authorities, and public. This will provide direct and immediate access to our findings for further development of personalised treatment, therapeutic targets and vaccines in future trials and clinical practice to improve the wellbeing of the EU population and beyond.",,2026,STATENS SERUM INSTITUT,7137450,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2022 +P23443,101003555,FIGHTING-OFF CORONAVIRUS (SARS-CoV-2) WITH BROAD-SPECTRUM ANTIVIRALS: ESTABLISHING ANIMAL VIRAL CHALLENGE MODEL,"Project coordinator: Professor Anna-Lena Spetz, MD, PhD, Stockholm University, Sweden Objectives of proposal: Our consortium 'ÄúFight-nCoV'Äù will accelerate preclinical development of new broad-spectrum antivirals for inhalation, building on breath-taking ongoing research. We will determine and characterize the antiviral activity and safety of three viral entry inhibitors (oligonucleotide, Macro-I, tweezer) against SARS-CoV-2 in vitro and in vivo. To enable this, we will build capacity for evaluation of antiviral efficacy against SARS-CoV-2 in vitro using viral pseudotypes and wild-type SARS-CoV-2 as well as in vivo in non-human primates. Safety studies will be performed according to OECD GLP guidelines. Expected results: We will establish a SARS-CoV-2 spike pseudotype system allowing a standardized high throughput evaluation of the antiviral activity of candidate drugs. We will have determined the antiviral efficacy of three novel broad-spectrum viral entry inhibitors: oligonucleotide, macromolecular polymers, and molecular tweezers. We will also build capacity for innovation and preclinical evaluation of our broad-spectrum antivirals and vaccines against SARS-CoV-2 by establishing a macaque challenge model. 'ÄúFight-nCoV'Äù will provide efficacy data of our drug candidates given intranasally in non-human primates challenged with SARS-CoV-2, enable an early and valuable outcome for stakeholders and the civil society. Timeline of proposal: Ongoing-24 months Key partners: Roger Le Grand, Director animal facility, CEA, France; Urban H√∂glund, CEO Adlego Biomedical, Sweden; Jan M√ºnch, Professor in Molecular Virology, UULM, Germany; Alexander Zelikin, Associate Professor, formulation expert, AU, Denmark; and Thomas Schrader, Professor of Chemistry, UDE, Germany.",,2022,STOCKHOLMS UNIVERSITET,3059658.34,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23444,961845,Rapid COVID-19 Passive Therapy Response Platform,"The SARS-CoV-2 pandemic requires the most serious and rapid healthcare response seen in modern history. The lag time between the emergence of the pathogen and the implementation of a licensed vaccine still remains an obstacle for prophylactic measures. In addition, how long immunity lasts for following COVID-19 infection is a big unknown. The development of immunity to the currently circulating SARS-CoV2 may not provide sterilising protection against subsequent coronavirus infections. If this were to be confirmed, it would add to the challenge of managing the pandemic. Short-lived passive immunisation with an anti-COVID-19 therapy is immediately required to treat infected patients and to 'Äòflatten the infection curve'Äô and to provide time for 'Äòherd immunity'Äô approaches. Devising an effective strategy requires an approach that is designed to exploit the extreme heterogeneity of the human anti-viral immune response. RemedyBio'Äôs Nanoreactor technology is such a system. It is the result of a 5-year research programme to develop a platform to rapidly and simultaneously analyse millions of single antibody-producing immune cells from an individual sample. In the context of COVID-19, this presents an opportunity to rapidly identify the best antibodies from the immune systems of COVID-19 convalescent patients from which to create a rapid passive therapeutic for those that are critically ill from the virus. Based on records from 1918/1919, it is plausible for the COVID-19 pandemic to wane in the late spring (in Europe), and come back as a second wave in the winter, which, as was the case in 1918, could be even worse than what we're facing now. COVID-19 is a global health problem and we need to be ready for this. This project is designed to combine novel discovery and delivery technologies to form a platform to rapidly identify, produce and deliver anti-viral neutralising antibodies to COVID-19.",,2022,REMEDY BIOLOGICS LIMITED,3000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P23445,101003627,Swift COronavirus therapeutics REsponse,"Coronavirus 2019-nCoV has become a worldwide public health emergency, and the lack of vaccines and drugs to immediately address this outbreak is painfully clear. Even if the epidemic can be stopped, the virus may return in the same or a modified form. More than vaccines and therapeutic antibodies, antiviral drugs can target highly conserved viral functions and have the broad-spectrum activity that is critical to combat current and future outbreaks. Since the 2003 SARS outbreak, as leading academic coronavirus researchers, we have collaborated to understand and inhibit coronavirus replication. We defined viral key functions, developed tools for inhibitor screening, and identified/engineered drug candidates. Until 2015, our collaborative efforts were supported by the FP7 SILVER project, but they have been continued until this very day. As European coronavirus experts, we now propose the SCORE project, supported by a leading pharmaceutical company. Virologists, biochemists, structural biologists, and medicinal chemists will collaborate in a state-of-the-art drug discovery/design program that targets 2019-nCoV. Our vast SARS-CoV-derived expertise and unique toolbox will be a major asset to achieve immediate impact. We will target the virus using 5 independent approaches: (i) using of (combinations of) FDA-approved drugs, (ii) targeting viral RNA synthesis, (iii) inhibiting coronavirus proteases, (iv) blocking virus entry, (v) discovery and development of new antivirals. This program will be supplemented with 2019-nCoV toolbox and animal model development. We aim to deliver proof-of-concept for selected compounds within 6-9 months, after which they will be offered for further use/development. This will contribute to short-term solutions for the on-going crisis and also pave the way for mid/long-term success in developing inhibitors that will be active against (evolving) 2019-nCoV strains, other SARS-like coronaviruses, and potentially (beta)coronaviruses at large.",,2022,ACADEMISCH ZIEKENHUIS LEIDEN,2807908.67,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +P23446,101045956,Biomarker and AI-supported FX06 therapy to prevent progression from mild and moderate to severe stages of COVID-19,"More than 2.7 million hospitalisations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. An average 14% of those patients with mild or moderate illness develop severe symptoms and are eventually admitted to the Intensive Care Unit (ICU). The most common treatment of patients in the first two stages of the illness, such as remdesivir and antibody therapies, have neither shown the desired effect nor prevented the progression of the disease to severe and critical stages of the illness. Interventions against SARS-CoV-2 are in high need to prevent admissions to ICUs, and would reduce the burden on patients and their families, clinical staff and the healthcare sector. Additionally, such interventions would help to provide ICU beds for non-Covid patients requiring immediate interventions, such as for heart or cancer surgery, both of which are often in need of planned free ICU beds. In COVend, our multidsciplinary consortium will deliver a new effective therapy against SARS-CoV-2 for the clinical management of the COVID-19 disease during mild and moderate stages, including for the prevention of disease progression to severe illness. This will be achieved by advancing a promising therapeutic candidate, FX06, from Technology Readiness Level (TRL) 7 to TRL9 through a multi-centre phase II/III clinical trial. COVend will study the influence of COVID-19 on endothelial cells (ECs) and the potential protective effect of FX06, and will apply -omics technologies, generate new algorithms and open-source software to carry out data analytics and modelling, and will develop health economic models to assess the socio-economic benefits and cost effectiveness of the new therapy. The COVend consortium unites expertise from different disciplines, including (cell) biology, ICT expertise for AI-based evaluations, pharma, economics and social sciences, as well as clinical expertise from 13 European countries.",,2024,JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN,11894023.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial | Prophylactic use of treatments,2021 +P23447,101015756,SUPporting high quality evaluation of COVID-19 convalescent Plasma thrOughoutT Europe,"Coronavirus disease 19 (COVID-19) is provoking the greatest global health crisis of this generation. With no vaccine or specific antiviral treatment available to date, the use of convalescent plasma (CP) from recovered COVID-19 patients has been considered a potential curative strategy. To demonstrate its efficacy and safety, clinical studies are ongoing or planned in various EU Member States. Unfortunately, there lacks a coordinated approach involving a large number of blood establishments (BEs) and clinical centres to harmonise protocols and guidelines, to standardise assays for characterising the potency of the plasma and to validate clinical outcome which will be of great importance to ensure that significant conclusions can be drawn. SUPPORT-E brings together major European BEs with world leading research capabilities with the aim to support high quality clinical and scientific evaluation of COVID-19 CP (CCP) and thereby achieve a consensus on the appropriate use of CCP in the treatment of COVID-19 across EU Member States. Hence, SUPPORT-E will advance the current state-of-the-art by delivering the much needed harmonised evidence-based recommendations with respect to the use of CPP in clinical trials and monitored access programmes for COVID-19 patients in Europe. Further, standardised informative in vitro assays providing scientific insights that could support such recommendations will also be developed. SUPPORT-E offers an EU-wide collaboration between Member States, BEs and clinical centres in order to close the knowledge gap and to ensure applicability of the recommendations for all EU Members States. SUPPORT-E represents the first European Union coordinated research effort on passive immunotherapy, sharing data and protocols in real-time and pooling efforts to decrease the time as much as possible for validating CCP as a valid therapeutic treatment and also providing a basis for further optimisation by combined approaches with other anti-viral treatments.",,2025,EUROPEAN BLOOD ALLIANCE,4503830.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23448,101005144,Robust Automation and Point of Care IDentification of COVID,"As of 30th March 2020, the COVID-19 outbreak has caused over 735,000 infections globally, claiming more than 35,000 lives. Rapid and definitive diagnosis of the specific SARS-CoV-2 is essential, while identifying other common viral and bacterial pathogens is beneficial in the management of treatment and in timely isolation of infected patients with overlapping clinical symptoms. A recent study has shown that 5.8% of SARS-CoV-2 infected and 18.4% of non-SARS-CoV-2-infected patients had other concurrent pathogen infections. Failure to distinguish different pathogens may lead to unnecessary antimicrobial use, cross-infection of mis-grouped patients and further spreading of the infection. Therefore, in response to the current outbreak, singleplex testing is not optimal, especially considering the virus may become permanently and globally endemic. Simple, sensitive and multiplex detection of all respiratory pathogens is technically challenging. In response to the need for faster and better detection of multiple respiratory pathogens, GeneFirst has developed a prototype using its innovative proprietary technology - MPA (Multiplex Probe Amplification) - to simultaneously detect and differentiate SARS-CoV-2 as well as 30 other common respiratory bacteria and viruses. This assay will allow for accurate, cost-effective and comprehensive diagnoses during the current outbreak as well as future routine diagnosis. In this project, the consortium aims to analytically and clinically validate (CE-mark) this assay on two automated platforms for Point-of-Care and core pathology testing. This strategy provides maximum flexibility in screening and triage, allowing better and faster care, alleviating pressures on healthcare systems and improving patient recovery rates. GeneFirst aim to commercialise the assay for ¬£8.50 ('Ǩ9.00) per test.",,2022,GENEFIRST LIMITED,3342450.3,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23449,101098201,PROposing Action to ConTrol and Impede betacoronaVirus Emergencies,"The COVID-19 pandemic caught the world unprepared. Vaccines and monoclonal antibodies (mAbs), developed in record time, mitigated the health and economic damages, however our reaction has always been one step behind the virus evolution, and emerging variants repeatedly escaped our interventions. The omicron variant escaped humoral immunity generated by most vaccines and mAbs by mutating immunodominant epitopes. The extremely potent mAb developed by our laboratory also lost potency against omicron. 'ÄØHere we propose to develop vaccines and monoclonals neutralizing existing and future variants of SARS-CoV-2 and other coronaviruses, by targeting immunologically subdominant regions which are less susceptible to antigenic variation. We will isolate mAbs from individuals who had infection and multiple vaccinations, whose repertoire is enriched in B cells encoding broadly neutralizing antibodies, to build a map of the broadly shared epitopes. Structural prediction and clustering of the immune repertoire through deep neural networks will be used to improve the breadth of coverage of the mAbs. The Monte Carlo-based sequence design of Rosetta and free energy perturbation calculations will be used to in-silico 'Äúdesign protein-binding proteins'Äù and identify newly designed immunogens which can be loaded on nanoparticles and used as vaccines. This approach will provide broadly protective mAbs and vaccines proactively designed to neutralize all variants of SARS-CoV-2 and new coronaviruses that are very likely to jump from animals to humans in the future. If successful, the approach to map subdominant epitopes and use of genomic and structural information to design mAbs and vaccines targeting subdominant, broadly conserved epitopes, will pave the way to approach other pathogens with high antigenic variability such as influenza and HIV viruses, Plasmodium spp. and antibiotic resistant bacteria. This will strongly increase European competitiveness in fighting infections.",,2028,FONDAZIONE TOSCANA LIFE SCIENCES,2623687.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Italy,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2023 +P23450,101088622,Investigating Virus-Host Interplay in Human Primary Models of Genetically Modified Respiratory Epithelium,"Respiratory viruses can rapidly spread worldwide with a devastating impact, as dramatically highlighted by the COVID-19 pandemic. In addition to the pandemic threat posed by influenza A viruses (IAV) or coronaviruses, respiratory viruses, including IAV, influenza B virus (IBV), seasonal coronaviruses and respiratory syncytial virus (RSV), are the cause of yearly epidemics, with a huge impact on human health. The vast majority of in vitro studies has been performed with model cancer cell lines. However, they share limited features with the primary cells found within the human respiratory epithelium. Robust and relevant, ex vivo models of human primary airway epithelia, cultured at the air-liquid interface (ALI) have been developed over the years and nicely recapitulate the structure and composition of the in vivo respiratory epithelium. Nevertheless, in depth studies on the genes and the potent innate immune, interferon (IFN)-induced, defences regulating viral replication in such pertinent models are still lacking. The InVIRium project will address this knowledge gap by combining a newly acquired expertise in the generation and gene editing of human ALI airway epithelia, with a strong expertise in CRISPR screens and virology. The objectives of InVIRium will be to explore in depth the relationships between major human respiratory viruses, SARS-CoV-2, IAV, IBV and RSV, and their relevant, primary target cells. InVIRium will characterize the IFN-stimulated-genes responsible for the potent antiviral state, explore the mechanisms of SARS-CoV-2 escape from the IFN system and define the landscape of host genes regulating respiratory virus infection in this physiologically relevant ALI model. InVIRium will bring a change of paradigm in the way we study respiratory viruses, by implementing cutting-edge approaches in highly pertinent human models and will gather fundamental knowledge that is currently lacking on the interactions between viruses and their primary target cells.",,2028,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,2723388.8,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2024 +P23451,961745,Increasing Survival of Patients with Severe SARS-CoV-2 Infection and/or Multi Organ Failure by up to 30% with ADVOS - ADVanced Organ Support,"ADVITOS` innovation 'Äì the ADVOS therapy system - has the potential to increase the survival of COVID-19 patients suffering from severe multi organ failure (MOF). First published clinical data show that ADVOS improves survival by up to 30% in critically ill patients on intensive care. The first COVID-19 patient with MOF is being treated with ADVOS in Germany at present with promising results. ADVITOS is a SME instrument Phase 2 beneficiary: ADVOS 880349 for device usability improvement, IoT integration, and market expansion (2.3m'Ǩ grant). Following the urgent EU call for corona solutions, we apply now for the blended finance option to speed up device production and installation in Germany and other EU countries. The applied funding and equity is necessary in therapy application, service and sales resources as well as accelerated clinical evidence for medical indication guidance. Integrating fluid-based blood oxygenation for comprehensive lung support and AI/digital capabilities will achieve additional therapy and outcome improvement. Each year, 60% of intensive care patients - 500,000 individuals in Western Europe and the US - die of MOF. The coronavirus outbreak will further increase this number dramatically as COVID-19 often leads to MOF. The innovative ADVOS therapy has the potential to revolutionize intensive care therapy of patients worldwide, as it is the 1st and only blood purification therapy combining liver, lung, kidney support and direct blood pH correction in 1 device (technology leader in removal of liver toxins and fast extracorporeal blood pH correction). It will help to save lives in the current Corona crisis. The ADVOS therapy is low-invasive as standard hemodialysis, so it can support by far more ICU patients than other devices (that have a higher risk profile). This relates especially to the removal of CO2 (by ADVOS) which relieves the lung and reduces the need/invasiveness of ventilation.",,2023,ADVITOS GMBH,1123296.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23452,101045989,SARS-coV2 variants Evaluation in pRegnancy and paeDIatrics cohorts,"Variants of concern (VoC) of SARS-CoV-2 raise the possibility of increases in transmissibility, severity and immune evasion. Children and pregnant women who have not been prioritised in the pandemic, are likely to be the last population for whom vaccines are approved and may have low uptake, increasing the risk of VoC arising in this population. Monitoring this group across regions is crucial given rapid changes in epidemiology due to interventions, vaccine rollout and viral evolution. VERDI (SARS-CoV-2 variants Evaluation in pRegnancy and paeDIatrics cohorts) will build on a long-standing infectious disease research and trial network (Penta) to address research questions on the impact of VoC in these vulnerable groups. VERDI'Äôs objectives are: i) track and characterise VoC in paediatric and pregnant populations across the globe; ii) understand effects of VoC on clinical outcomes (short/longer term), vaccine effectiveness and transmission characteristics; iii) model outcomes and impacts of VoC; iv) develop evidence-based recommendations for control of COVID-19. VERDI will achieve these objectives by bringing together a diverse range of cohort studies including large scale national and regional level population-based cohort studies from the EU and beyond, providing a unique opportunity for harmonised analysis of data on VoC from a range of sources (e.g. electronic health records, bespoke cohort studies, household transmission studies, screening programmes). We will facilitate expansion of existing studies, e.g. replicating ongoing European household studies elsewhere. Through this approach, VERDI will expand and enhance existing cohort networks, including promoting flexibility to adapt to future emerging infections. The project will improve understanding of the epidemiology and impact of VoC, leading to robust recommendations for control in a range of global settings as well as developing preparedness for future health emergencies.",,2025,UNIVERSITA DEGLI STUDI DI PADOVA,17858894.84,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing | Digital Health,,,Italy,,Clinical characterisation and management | Epidemiological studies,Disease pathogenesis | Post acute and long term health consequences | Impact/ effectiveness of control measures,2021 +P23453,101046084,Equine Polyclonal antibodies Immunotherapy against COVID-19/SARS-CoV2'ÄìVOC,"The highly contagious SARS-CoV-2 virus has generated an unprecedented pandemic with global dramatic public health and socio-economic consequences need an urgent mitigation. Despite the progression of the global use of efficient vaccines, an increased transmissibility of variants of concern (VOC) is predominantly observed. The reduced sensitivity of VOCs to neutralizing response could become a serious obstacle for efficient vaccination. In the absence of approved specific antiviral therapies for vaccinated-non-responders and the scarce anti-inflammatory therapies, passive immunotherapies with polyclonal immunoglobulins could be considered a part of the solution. The main objective of EPIC-CROWN is to rapidly assess, in multicentric clinical trials (phase IIa, 16 patients and IIb, 400 patients), an EMA-authorized antiviral immunotherapy based on potent and broad equine neutralizing anti-SARS-CoV-2 polyclonal F(ab'Äô)2 antibodies in COVID-19 patients, including VOC carriers. In order to save lives and reduce the use and costs of critical care, this therapeutic solution expect to reduce at least by 50% ICUs admissions and a highly significant mortality rate of treated patients. To optimize the indications for the treatment, potency and breath of F(ab'Äô)2 against variants will be assessed in in vitro and in an animal model as well as prospective studies will respectively be done on immune assessment in treated patients and on mitigation of exacerbated immune responses in vivo. Fab'Äôentech will coordinate EPIC-CROWN-2 formed by outstanding experts in different project domains that include clinical trials (HISS, Greece), virology (IMAS12, Spain), and immunopathology models and mitigation (BNITM, Germany - IRD, France). Most of them having already been working together in European projects. Importantly, EPIC-CROWN-2 will be integrated as part of both the large European trial network EU-RESPONSE and the multinational European Adaptive Platform Trial 'ÄúSolid Act"".",,2023,FABENTECH,11065563.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Therapeutics research, development and implementation",Pre-clinical studies | Phase 2 clinical trial,2021 +P23454,101100758,Hit-to-Lead Development of potent broad-spectrum coronavirus fusion inhibitors,"The Covid-19 pandemic emphasized the urgent need for efficient broad-spectrum antiviral drugs against potential future coronaviruses (CoV) strains that may cause the next COVID pandemic. A critical stage during infection is the fusion of the viral envelope with the host-cell membrane, which depends on the conserved S2 domain of the viral Spike (S) protein. Hence, targeting the S2 domain is a promising approach to achieving pan-CoV inhibition. Since MERS- and SARS- S proteins bind to different cellsurface receptors through the rapidly diversifying S1 domain, we reasoned that compounds that inhibit both must target the S2 domain. We developed and performed a robust fluorescence-based high-throughput screen of 173,227 unique compounds and classified them based on their ability to inhibit infection of pseudoviruses bearing either MERS or SARS-2 S proteins at single-cell resolution. To our knowledge, this is the largest screen performed to date. This analysis identified several potent broad-spectrum small molecules that inhibit S protein mediated infection at sub-micromolar concentrations. Moreover, the compounds we discovered obey Lipinski's rule of five, indicating that they can potentially become drugs to prevent viral transmission. This project aims to develop two of the most promising broad-spectrum CoV small molecule inhibitors to create more clinically ready compounds with up to 100% inhibition activity that could be administered orally to reduce hospitalizations, prevent chronic effects, and reduce mortality. The technical work in the project is focused on lead optimization leading towards broad-spectrum antiviral drugs against future outbreaks of bat-borne viruses. The project also comprises pre-commercialization activities, where IP protection and commercialization planning are the core activities. Eventually, we will expect our developed compound(s) to boost the market for antiviral therapies for bat-borne viruses.",,2024,WEIZMANN INSTITUTE OF SCIENCE,148500,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),European Commission,Europe,Europe,Europe,Unspecified,,,,Israel,,"Therapeutics research, development and implementation",,2022 +P23455,960753,"Secure, safe, sustainable and affordable on-site generation of Hydrogen Peroxide","Hydrogen peroxide (H2O2) is one of the world'Äôs most widely used chemicals 'Äì it is a powerful oxidant and disinfectant utilized across water and wastewater treatment (WWT); pulp, paper and textile; medical, and electronics industries. It is highly effective against a wide range of pathogens, including SARS-CoV-2 (cause of COVID19), as well as in facilitating the breakdown of human-generated pollutants. The H2O2 market is valued at over 'Ǩ19.5B / annum at the point of use. While H2O2 itself is 'Äúgreen'Äù 'Äì decomposing to pure water and oxygen 'Äì today'Äôs supply chain is far from it. The global consumption of over 6.5M Tons is produced in centralized chemical plants, emitting greenhouse gasses (GHG) equivalent to the emissions of 3M cars, and outputting over 60M Tons / annum of toxic waste . Delivery from these centralized plants to millions of distributed points of use requires transportation of a high-concentrate, highly-explosive solution, break-down to manageable units, and dilution from 30% - 70% solutions down to a few parts per million (ppm) - a complex, hazardous, costly, and increasingly regulated supply chain.This is also vulnerable supply chain - in the present COVID19 outbreak a shortage is already felt in the market. Our goal is to replace today'Äôs GHG emission and toxic-waste intensive, hazardous, prone to supply interruptions, and costly H2O2 supply chain, with our PeroxyPro 'Äì the world'Äôs first and only commercial technology solution for the on-site generation of hydrogen peroxide through direct electrochemical synthesis, using only water, electricity and air as inputs. PeroxyPro will secure consumable-free supply of a highly effective biocide and oxidizer in critical applications; will displace centralized, GHG and toxic-waste intensive production, with an eco-friendly, zero-emission and zero-waste, distributed generation process; and will replace a hazardous and costly supply chain with on-site, on-demand and safe generation directly at the point of use.",,2022,HPNOW APS,2001160,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23456,101003653,Nanobodies and antibodies against 2019-nCoV,"Overview: As of Feb 12th, 2020, the death toll of the 2019-nCoV (COVID-19) epidemic has surpassed 1000, rapidly eclipsing the total mortality of SARS. It has a current death rate estimate of around 2 deaths per 100 confirmed infections, is experiencing phenomenal growth in mainland China, and has the potential to spread globally over the coming months. While a vaccine may be useful for future epidemics of a similar virus, it is not clear that such a vaccine can be produced at a speed and scale sufficient to impact the current epidemic. Objective: Antibodies form the basis of a robust adaptive immune response to viral disease. Nearly all licensed vaccines mediate protection through the activity of antibodies and where vaccines are not available, passive infusion of monoclonal antibodies can fill the gap and control the infection. The overarching goal of the CoroNAb consortium is to rapidly identify, validate, and disseminate pre-clinical protein therapeutic candidates with neutralizing activity against 2019-nCoV, and to recommend where their use would be maximally effective. Expected results: Over the course of the project, we expect to design and synthesize recombinant variants of nCoV glycoproteins for immunization in mice, alpacas and macaques in order to generate and characterize multiple nCoV-neutralizing antibodies and nanobodies. We will develop efficient assays for the testing of such antibodies and exploit novel computational workflows to improve neutralizing antibody potency. Finally, we will employ mathematical modeling of the 2019-nCoV epidemic for forecasting intervention effectiveness. Timeline: We expect the project to deliver a number of nCoV neutralizing anti- and nanobodies of increasing potency over a 2 year period from start date.",,2022,KAROLINSKA INSTITUTET,3021107.22,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +P23457,101040297,Going Viral: Music and Emotions during Pandemics (1679-1919),"Within day of Covid-19 reaching Europe in early 2020, music had emerged as one of the most prominent media for emotional engagement with the effects of lockdown, sickness and grief. Its remarkable primacy for expressing, navigating and shaping emotional pandemic experiences was quickly picked up by researchers and journalists who showed an immediate interest in finding evidence both for the role of music in past pandemics and for continuities across time. It quickly transpired, though, that they lacked established categories, shared methodologies and sufficient historical knowledge to describe and to compare the phenomenon adequately. The study of music in pandemics, and especially of its emotional significance, is both underdeveloped and urgently needed - and has the potential to constitute a major new field of research on music, emotions and pandemics alike. GOING VIRAL will be the first study to provide a comparative history of the imbrication of music in the emotional experiences of pandemics. Its major research aims are - to develop an innovative conceptualisation and methodology for studying music and emotions across history, building on the equally well-regarded approaches ""musicking as social practice"" and ""emotions as embodied practices""; - to generate ground-breaking historical knowledge about music's emotional dimensions in three major pandemics - the Plague, Cholera and Spanish Flu - in Vienna beginning in the 17th century, highlighting both difference and continuity; - to provide a solid conceptual, methodological and historical foundation for comparative studies on music, emotions and pandemics across a vast range of disciplines. GOING VIRAL's results will not only be applicable in related historical settings but also enable a meaningful interdisciplinary discourse with the social and natural sciences about music end emotions in pandemics, including Covid-19.",,2027,UNIVERSITAT FUR MUSIK UND DARSTELLENDE KUNST WIEN,1499379,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Yersiniaceae,H1,H1N1,,,,,,,Pandemic-prone influenza | Plague,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,"Secondary impacts of disease, response & control measures",,2022 +P23458,101126531,Late-stage clinical development of Chikungunya vaccines in endemic countries (CHIKV) and Controlled Human Infection Models for SARS-CoV2 and other beta coronaviruses (CHIM).,"A Framework Partnership Agreement (FPA) between the Coalition for Epidemic Preparedness'ÄØInnovations (CEPI) and the European Union (EU) was signed in April 2019, to finance and coordinate the development of new medical countermeasures to prevent and contain infectious disease epidemics, which are of particular concern to low- and middle-income countries. As part of the FPA, a call for proposals (CfP) was launched jointly with the EU and supported the preclinical development of Rift Valley Fever Virus vaccines and the late-stage development of Chikungunya virus vaccines (CHIKV). While previous funding has led to the development of pre-licensure CHIK vaccines, in this current application we like to further advance our CHIK vaccine programme, and support CHIK vaccines that are near or have achieved regulatory licensure by supporting their clinical development into phase IV clinical trials to increase our understanding of the long-term safety, durability of protection, and effectiveness against virologically confirmed disease. Furthermore, we would like to expand the use indication by supporting clinical trials in vulnerable populations, including children, immunosuppressed and pregnant women.'ÄØ As part of this grant application, we also like to launch a CfP on Controlled Human Infection Models (CHIM). The overall objective of the CHIM proposal is to support research projects that increase knowledge in vaccine-induced mucosal immunity and advance the development of transmission-blocking vaccines against coronaviruses and other potential respiratory viral threats.'ÄØThe expected outcome of this CfP is to create a global network of experts conducting CHIM at a high level of consistency and reliability. This current grant application seeks to leverage 'Ǩ70M from Horizon Europe, which will be supplemented with 'Ǩ30M from CEPI making a pool of 'Ǩ100M. Awards will have a 36'Äì48-month duration and will be administered by the CEPI secretariat.",,2028,COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS,74900000,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women | Other,Unspecified,Clinical,"Clinical Trial, Phase IV | Unspecified",Coronavirus | Other,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS) | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Norway,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2023 +P23459,101088587,Rational and Simulation-Supported Design of Inhalable RNA Nanocarrier,"The overarching goal of RatInhalRNA is to computationally predict and develop efficient formulations for pulmonary RNA therapy. New RNA formulations are imperative for clinical RNA delivery beyond the liver. The lung offers undruggable targets which could be treated with RNA therapeutics. However, approved siRNA formulations are not suited for pulmonary delivery due to instability in lung surfactant and during nebulization. Hence, it is my aim to rationally design inhalable and biocompatible polymer-based siRNA formulations for efficient siRNA delivery to the lung. While biomaterials are commonly optimized empirically via one-variable-at-a-time experimentation, I am the first to combine Design-of-Experiments (DoE) with Molecular Dynamics (MD) Simulations and Machine Learning (ML) to accelerate the discovery and optimization process of siRNA nanocarriers towards the metrics of gene silencing efficacy and biocompatibility at reduced wet-lab resources. In RatInhalRNA, I will synthesize amphiphilic polyspermines and will prepare siRNA-loaded nanoparticles by microfluidic assembly for experimental assessment of physico-chemical parameters as well as in vitro and in vivo gene silencing efficacy in coronavirus infection models. I will assess siRNA binding of the polyspermines via MD simulations and will analyze the contribution of the nanoparticle design factors on experimental and computational readout responses of the DoE. I will train a support vector machine for supervised ML and will generate models to identify areas of interest. Based on the predictions, I will test additional formulations to obtain a validation dataset for the assessment the ability of the ML algorithm to identify design properties of efficient siRNA nanoparticles for pulmonary delivery. RatInhalRNA will enable me to predict favorable siRNA nanoparticle characteristics in the future prior to polymer synthesis thereby reducing experimental work and improving sustainability and animal welfare.",,2028,LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN,2180000,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P23460,101113460,Sustainable use and integration of enhanced infrastructure into routine WGS-based surveillance and outbreak investigation activities in Portugal,"The Portuguese National Institute of Health (Instituto Nacional de Sa√∫de Dr. Ricardo Jorge - INSA) is the State reference laboratory whose mission is to contribute to public health gains through research and technological development. The Genomics and Bioinformatics Unit and the Technology and Innovation Unit at INSA have been in charge, over the last decade, of performing the genome-based surveillance of infectious diseases at the national level, including the monitoring of SARS-CoV-2 and Monkeypox virus emergence and dissemination. INSA successfully applied to the previous HERA Incubator funding mechanism through ECDC, which aimed at strengthening the Portuguese capacity for whole-genome sequencing (WGS) and/or RT-PCR essentially to respond to the COVID-19 pandemic. Considering the need to consolidate the implemented infrastructure and to optimize the processes and workflows between the various actors, we are now, with 'ÄúGENEO'Äù, addressing the following main lines of action: 'Ä¢ Extend and consolidate highly specialized human resources contracts and positions 'Ä¢ Ensure medium-term computer storage capacity for genomic data 'Ä¢ Implement a Quality management system for genomic sequencing 'Ä¢ Conduct training in genomic epidemiology for health professionals 'Ä¢ Develop efficient communication strategies of project results The aimed integrated laboratory management, WGS workflow optimization and enhanced data communication will allow the rapid detection of emerging cross-border pathogens and the robust monitoring of circulating microbial threats. This will strongly influence the decision making process at the level of national and international public health and will contribute for the elaboration and implementation of measures to control potential epidemics.",,2026,INSTITUTO NACIONAL DE SAUDE DR. RICARDO JORGE,1583250.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Poxviridae | Novel Pathogen,,,,,,,,,COVID-19 | Mpox | Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Portugal,,Epidemiological studies,Disease surveillance & mapping,2022 +P23461,101103188,BUILDING SCALABLE PATHOGEN GENOMIC EPIDEMIOLOGY FOR ETHIOPIA,"The 21st century witnesses increased incidence of epidemics (Zika, dengue, Ebola, SARS), with as latest highlight the recent COVID-19. Following the outbreak of several infectious diseases during the last few decade, the need for generating real-time pathogen genomic data for public health action has become more important than ever. In the African context, infrastructure, human resource capability, data analysis, including bioinformatics, lack of linkage between clinical, epidemiological, and pathogen genomic data as well the interaction between clinicians, researchers and decision makers are some of the major challenges. The aim of the EpiGen project is to build a capacity for integrated pathogen genomic surveillance for informed public health decision process. The overarching specific objectives include strengthening collection and analysis of clinical and epidemiological data, enhancing the capacity and capability for pathogen genomic sequencing, including strengthening the laboratory infrastructure, human work force, pathogen genomic data analysis, and the integration of metadata with genomic data, developing and implementing innovative digital diagnostic platforms, creating semi-real time mobile phone applications for policy decisions, and promoting communities of practice and knowledge exchange through fostering African collaboration and networking in the domain of pathogen genomic surveillance for infectious diseases. EpiGen project'Äôs multi-disciplinary consortium is drawn from several institutions from Ethiopia engaged in National Public Health Programs, and EU partners (The Netherlands, Spain and Germany). Overall, the model approach proposed by EpiGen will enhance Ethiopia'Äôs national effort in mitigating the threat of infectious diseases. The implementation of a national genomic-informed surveillance for infectious diseases will play significant public health role towards contributing to disease prevention and control programmes in Ethiopia and beyond.",,2028,STICHTING AMSTERDAM INSTITUTE FOR GLOBAL HEALTH AND DEVELOPMENT,5884034.86,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Filoviridae,,,,,,,,,Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease | Zika virus disease | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P23462,101057302,SARS-CoV-2-induced activation of pathogenic endogenous retrovirus envelope HERV-W: towards personalized treatment of COVID-19 patients,"Severe COVID-19 disease and the high frequency of its long-term complications are now a major health problem worldwide. Due to the significant heterogeneity of COVID-19 disease profiles, biomarkers that allow either the identification of patients at high risk for developing severe forms of COVID-19 and its long-term complications, or guide personalized treatment options, are scarce. The HERVCOV project aims to analyze the role of human endogenous retroviruses (HERVs), known for their high pro-inflammatory potential, in the immunopathogenesis of COVID-19 and to identify and evaluate a set of biomarkers which will be important for the diagnosis, prognosis and follow-up of COVID-19 patients and their prioritization for targeted therapy. Recent data from the consortium has demonstrated that HERV-W envelope protein is highly expressed in lymphocytes of COVID-19 patients and correlates with inflammatory markers and respiratory outcome of the disease, strongly suggesting the role of HERVs in COVID-19 pathogenesis. The project aims to assess the biological pathways and functions that underlie the association of HERV expression and activation with severe COVID-19 forms and related complications. Biomarkers based on HERV pathogenic protein activation, SARS-CoV-2-specific immune responses, cytokine production and mandatory medical blood analyses for COVID-19 clinical monitoring will be studied in samples from different forms of COVID-19: acute, post- neuro- and long-COVID patients. Parameters will be determined that predict the clinical course of the disease and aggravation of SARS-CoV-2-induced symptoms and allow potential clustering of different bio-clinical profiles of COVID-19 patients. Diagnostic and prognostic panel(s) ?translated? from our fundamental research and subsequent evaluations of HERV-associated biomarkers will be assessed to define novel indicators in precision medicine-based therapeutic strategies, leading to individualized medical treatment in COVID-19.",,2027,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,7120003.28,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Prognostic factors for disease severity",2022 +P23463,101040914,Interrogating RNA-protein interactions underlying SARS-CoV-2 infection and antiviral defense,"The global COVID-19 pandemic underscores the need to better understand its causative agent, SARS-CoV-2, and the various other emerging viruses threatening human health. Like many human viruses, SARS-CoV-2 utilizes RNA as its replicated genetic material and its template for translating the virus's proteins. Ongoing research into SARS-CoV-2 and other RNA viruses has largely focused on understanding the function of their encoded proteins, revealing key roles in host cell entry, viral replication, and immune suppression. In contrast, little is known about the set of viral RNAs and how they interact with host machinery as part of a virus's replication cycle in infected cells. My group discovered a large collection of viral and host proteins that bind the genomic and subgenomic RNAs of SARS-CoV-2 during infection. This collection provides an excellent starting point to work toward the goal of my proposed ERC Starting Grant project: decoding how these interactions shape the viral RNA life cycle and contribute to antiviral defense mechanisms. My overarching hypothesis is that SARS-CoV-2 dynamically modulates RNA-protein interactions in the host to facilitate functions of genomic and subgenomic viral RNAs at different stages of the replication cycle. To test this hypothesis, I have devised three research objectives: 1) Decode mechanisms of host-mediated control over the life cycle of SARS-CoV-2 RNAs. 2) Map with temporal resolution which host cell proteins engage each SARS-CoV-2 RNA type. 3) Elucidate the role of host proteins that moonlight as RNA binders in SARS-CoV-2 infections. If successful, this project will identify novel pro- and antiviral host factors in SARS-CoV-2 infections and reveal underlying RNA regulatory mechanisms. In turn, these insights will provide an RNA-centric view of viral infections and identify candidate factors and pathways as therapeutic targets to treat viral diseases.",,2027,HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH,1575000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P23464,101057100,The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine,"The consequences of SARS-CoV-2 exposure range from a lack of infection to lethal COVID-19. This immense inter-individual clinical variability is the key scientific and medical enigma in the field. While age and certain co-morbidities are known to influence disease outcome, these parameters do not explain all variation. In addition, there are other SARS-CoV-2 phenotypes of clinical importance: multisystem inflammatory syndrome in children and adults (MIS-C/A), and longCOVID. An important breakthrough to unravel the pathogenesis of COVID-19 came from our two Science papers that were recognized by Nature among the top 10 discoveries of 2020. We found that about 4% of patients with critical COVID-19 pneumonia had inborn errors of immunity (IEI) that impair TLR3- and IRF7-dependent type I interferon (IFN) immunity and at least 10% of the patients carried pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs. These findings pave the way for further studies of COVID-19 pneumonia and other SARS-CoV-2 infection phenotypes and form the basis of the present research proposal, UNDINE, which follows a ""bed side to bench"" and ""bench to bed side"" approach, with the following objectivies i) to decipher the genetic and immunological basis of the various SARS-CoV-2 disease manifestations, to identify individuals at increased risk of critical COVID-19, post-infectious immunological complications, and vaccine failure iii) to develop ready-to-use diagnostic tests for large-scale detection of auto-Abs to type I IFNs and propose novel preventive and therapeutic approaches, based on the pathogenesis of SARS-CoV-2 infection for translation into personalised medicine. To achieve these goals, our project will coordinate a European multidisciplinary and translational research effort relying on a strong and synergistic combination of assets, including unique cohorts from 11 EU countries and state-of-the art human genetic, immunological and virological expertises and technologies.",,2026,AARHUS UNIVERSITET,7188408.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity",2022 +P23465,101046203,Beyond COVID,"Beyond-COVID (BY-COVID) aims to provide comprehensive open data on SARS-CoV-2, and other infectious diseases across scientific, medical, public health and policy domains. The project will have a strong emphasis on mobilising raw viral sequences, helping to identify and monitor the spread of SARS-CoV-2 variants. It will further accelerate access to and linking of data and metadata on SARS-CoV-2 and COVID-19, enable federated data analysis conform with data protection regulations, and harmonisation and management of meta-data and sample- identifiers, as well as long-term cataloguing to ensure interoperability of national and global efforts. BY-COVID will align with the One-Health approach building on the latest technological advances, exploiting and contributing to the European Open Science Cloud capabilities for data access and federation as well as relevant standards and policies for managing, sharing and reusing research data, and work closely with the proposal funded through the sibling-topic from the emergency call (HORIZON-INFRA-2021-EMERGENCY-02). BY-COVID will integrate established national and European infrastructures including ELIXIR, BBMRI, ECRIN, PHIRI and CESSDA. It will build on existing efforts, such as the COVID-19 Data Platform and the Versatile emerging infectious disease observatory project (VEO), thereby maximising efficiency. Synergies with the European Health Data Space will be developed. BY-COVID is a truly interdisciplinary (55 partners from 19 countries) project bringing together stakeholders from the biomedical field, hospitals, public health, social sciences and humanities in an unprecedented and unique effort and will increase European readiness for future pandemics enhance genomic surveillance and rapid-response capabilities. The outputs of the project will allow scientists across multiple domains, including SMEs and industry, to access a range of data that will generate new knowledge on infectious disease.",,2024,EUROPEAN MOLECULAR BIOLOGY LABORATORY,13920000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Pathogen morphology, shedding & natural history",2021 +P23466,101057775,The pandemic within: tackling brain vulnerability in COVID19 at high resolution: NEUROCOV,"The COVID19 pandemic has shown our health care fragility vis a vis novel pathogens, with a global disruption on societal welfare. Despite the towering success of vaccine development, lack of preparedness on integrative clinical and molecular phenotyping has emerged with clarity and highlights the need to scale translational efforts for personalized prevention and therapy. Of particular concern are the long-term consequences of SARS-CoV-2 infection with high and rising prevalence of chronic manifestations referred to as Post-COVID. Among these the neurological and psychiatric complications stand out for frequency, lack of treatment and devastating impact of their effects at pandemic scale. Here, we tackle the cognitive and neurodegenerative complications of COVID-19, referred to as NeuroCOVID, as a ticking pandemic within the pandemic that requires an innovation leap across disciplines. We pursue a multi scalar approach that reaches from epidemiology and mechanistic interrogation of host/virus interplay at single cell resolution through predictive modelling all the way to validation of biomarkers and repurposed drugs. The aim is to anticipate and effectively manage personalized trajectories of NeuroCOVID vulnerability and their impact at population level. For this we leverage two leading national health registries and three clinical cohorts to characterize the phenotypic spectrum of NeuroCOVID, its risk factors and its socioeconomic burden at high definition. We pioneer innovative robotics to scale brain organoid modelling and combine it with single cell multiOMICs and AI analytics to dissect the principles of the individual host response and render experimentally actionable the authentic genetic backgrounds of differential SARS-CoV-2 sensitivity. Through a substantive engagement of patients'Äô collectives and health care stakeholders, upstream integration of innovative pipelines streamlines translation and operationalizes precision medicine for emerging medical needs.",,2027,DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV,8384036,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2022 +P23467,101016167,Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic: ORCHESTRA,"The ORCHESTRA project provides an innovative approach to learn from the SARS-CoV-2 health crisis and derive recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population cohorts in European and non-European countries. Data analysis through a federated learning technique supported by advanced modelling capabilities will allow the integration of epidemiological, clinical, microbiological and genotypic aspects of population-based cohorts with environment and socio-economic features. The ORCHESTRA cohort will include SARS-CoV-2 infected and non-infected individuals of all ages and conditions and thereby enabling a retrospective evaluation of risk factors for the disease acquisition and progression of the disease and prospective follow-up aimed at exploring long-term consequences and analysis of vaccination response when vaccines will be available. To better address these research questions, the ORCHESTRA-cohort will include adequately sampled representatives of general populations, COVID-19 patients and special 'Äòat risk'Äô populations of fragile individuals and health-care workers. The project will assess also health costs of COVID-19 with special emphasis on delayed health services in the fragile populations. The participation of non-European and Low-Medium Income Countries and a Global COVID-19 Guidance group of major stakeholders and investigators from successful clinical trials addressing therapeutic approaches to COVID-19, ensures inclusion of all expertise needed and translation of recommendations to different social and economic settings. The project will significantly impact on the responsiveness to SARS-CoV-2 and can be used as a model for responsiveness for new public health threats.",,2024,UNIVERSITA DEGLI STUDI DI VERONA,33465165.6,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Italy,,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2020 +P23468,101102366,"Enhancing Whole Genome Sequencing (WGS), national infrastructures and capacities to respond to the Covid-19 pandemic in Italy","Despite a reduction in the number of clinical severe cases of COVID-19, SARS-CoV-2 circulation increased, driven by waning vaccine effectiveness, novel viral variants and the progressive relaxation of non-pharmaceutical interventions. The possibility of a genetic drift of SARS-CoV-2 towards novel prevalent variants with uncertain consequences on the epidemiology and clinical presentation of COVID-19 exists. In Italy, genomic surveillance of SARS-CoV-2 is performed through periodic prevalence surveys, continuous sequencing in specific target-groups and periodic sequencing of raw sewage samples. While specific national funding has been established for some sequencing activities, the sustainability of periodic prevalence surveys is still uncertain. In addition, the completeness, timeliness and quality of the sequences uploaded to the national genomic surveillance platform Italian COVID-19 Genomic (I-Co-Gen) have margins of improvement and the reports produced currently do not integrate data from different SARS-CoV-2 surveillance flows in a common analysis. The project aims to: 1. Support the ongoing enhancement of the Whole Genome Sequencing capacity of the laboratories within the Italian genomic laboratory network and the periodic conduction of prevalence surveys, 2. Support the consolidation and quality of centralized genomic data collection and the establishment of innovative integrated data analysis of genomic and epidemiological data. In this view, the project will significantly contribute to strengthen laboratory preparedness and response, build capacity on genomic surveillance and innovate data analysis through the integration of human genomic, epidemiological and environmental sectors, also using statistical and mathematical models. The project will be coordinated by the Istituto Superiore di Sanit√† as national competent authority, and will involve both the Ministero della Salute and the Fondazione Bruno Kessler for their respective specific expertise.",,2025,ISTITUTO SUPERIORE DI SANITA,3602883.82,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Health Systems Research","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping | Health information systems",2023 +P23469,101137033,Crimean-Congo Haemorrhagic Fever Vaccine and Immunotherapy,"The CCHFVACIM project is an ambitious collaborative effort aimed at developing both prophylactic and therapeutic effective countermeasures against Crimean Congo Haemorrhagic Fever Virus (CCHFV), one of the most threatening vector-borne pathogens, widely distributed, including in the European continent. Deep structural biology studies on viral glycoproteins and investigation of the immunogenicity of the viral antigens will be combined with optimisation of an mRNA vaccine candidate against the virus and characterisation of the resulting protective immunity, as well as with the development of immunotherapeutic monoclonal antibodies (mAbs) based on CCHFV'Äôs antigenic targets. To achieve the overarching goals, the CCHFVACIM project will build on the success of previous projects such as CCHFever (FP7), CCHFVaccine (H2020) and go the extra mile by initiating a unique One-Health platform strategy to address different aspects of this severe public health threat. On one hand, the project will use several advanced animal models (mice, sheep, and non-human primate) to assess and compare the efficacy of mRNA vaccine candidates, mAbs and therapeutic mRNA; on the other hand, it will establish a biobank from CCHF patients to build up a pipeline for the production of mAbs against CCHFV from their B cells. Importantly, the project will also contribute to capacity building of European infrastructures, with the establishment of a platform on mRNA-based vaccine at one of the partner institutions. Ultimately, CCHFVACIM will permit to develop a road map to bring the most efficacious vaccine candidates and immunotherapy tools to clinical trial Phase I in humans. The project results will be widely disseminated among the scientific community, public health authorities, non-governmental organisations, outbreak management teams, and hospitals, with the final scope of both contributing to contain the burden of CCHF disease and increasing preparedness to new outbreaks.",,2028,FOLKHALSOMYNDIGHETEN,17279368.2,Animals | Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2024 +P23470,101045949,"ExeVir's XVR011, a best in class nanobody-based biology that broadly neutralizes SARS-COV-1 and SARS-COV-2","XVR011, ExeVir's clinical lead candidate has emerged from scientific research from labs of highly regarded virologist Xavier Saelens and biochemist Nico Callewaert. Nonclinical data has recently been published in Cell and a preprint on BiorxIV. XVR011 is a nanobody-Fc fusion, has best-in-class potential, neutralizes SARS-CoV-2 and minimizes the development of lung damage in hamsters. The lama-derived single-domain antibodies are smaller than human antibodies and can attach to parts of a virus that are difficult to access for the human immune system. XVR011 inactivates spike proteins and sterically blocks spike binding to ACE2, preventing virus from entering a human cell, stopping viral replication; this supplements the patient's own immune response in a critical time window during which many COVID-19 patient's immune system reacts too slowly, giving it more time to do its job and eliminate the virus. It binds to a unique highly conserved epitope in the viral receptor-binding domain. Its epitope is much less susceptible to human antibody immunity pressure that can lead to viral escape, resulting in retained potency against such escape variants. It thus neutralises the rapidly spreading SARS-CoV-2 variants, and exhibits a unique, wide scope binding across the Sarbecovirus clades. Furthermore, XVR011 has been optimized for stability, safety and manufacturability. XVR011 received approval from the Belgium regulators to move into its Phase 1b. Seven IP patents were filed early on during the pandemic. ExeVir has surrounded itself with both a team of experienced entrepreneurs and is backed by a mix of private and public experienced partners and has a strong board of directors bringing with expertise across the whole value chain. The objectives of this proposal is to demonstrate XVR011 safety and efficacy in a global Phase 2; to strengthen its nonclinical package including neutralising variants data, set-up its manufacturing process and progress its regulatory pathway.",,2022,EXEVIR BIO,11190107.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Phase 1 clinical trial | Phase 2 clinical trial",2021 +P23471,101028945,Optimizing treatment of cancer patients infected with COVID-19 and other preconditions using mathematical modelling,"Cancer patients are of high risk to develop severe COVID-19, which has a negative impact on their clinical management. Cancer therapy and COVID-19 severity can be also affected negatively by preconditions, including obesity, diabetes, hypertension and advanced age, as well as by the gender. To help cancer patients suffering from COVID-19 and the other preconditions as soon as possible, it will be necessary to repurpose existing and well tolerated drugs - alone or in combination. To accelerate this process, we propose to develop an in silico systems biology approach to model the known biology of SARS-CoV-2 infection and the action of approved drugs overlaid on the underlying pathophysiology of cancer patients with different disease states, preconditions and gender. The proposed mathematical framework will mechanistically model the COVID-19 progression in the context of cancer. We will also simulate the effect of COVID-19 in this patient population and explore the efficacy of various treatment regimens to identify synergistic combinations as well as optimal schedules for therapy. Robust model validation will be performed using data from the Massachusetts General Hospital patient database (host of outgoing phase). This is a very timely research because the proposed mechanism-based model will reveal novel strategies to optimally combine current and emerging treatments for COVID-19 in cancer. Importantly, the proposed model will not be limited to COVID-19 but it will set a mathematical framework for the optimal treatment of cancer patients contracted by any infectious diseases. The fellowship will allow the applicant to substantially built upon his previous experience and strengthen his overall scientific abilities. In particular, he will expand his knowledge in tumor/virus biology, cancer research and clinical translation, will enrich his mathematical modelling capabilities and the analysis of complex biological systems that involve more than one medical conditions.",,2024,UNIVERSITY OF CYPRUS,310045.56,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Cyprus,,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P23472,101018100,PROPOSAL FOR FUNDING RESEARCH DEVELOPMENT AND MANUFACTURING OF VACCINE AGAINST COVID-19,"Funding of research and innovation programmes for the development of novel SARS-CoV-2 vaccine against COVID-19 disease The overall objective is to leverage co-funding from the European Commission to support CEPI'Äôs COVID-19 vaccine programme development efforts. The COVID-19 outbreak has in a short timeframe grown to a global pandemic of historic proportions, with detrimental humanitarian and economic consequences. All evidence now suggests that eradication of COVID-19 is not feasible and that we face a global public health crisis which is unprecedented in modern times. At present there are no treatments, and there is no vaccine. Investing in vaccine development now is an investment in the future health for all in our societies and a return to social and economic development 'Äì both in Europe and in the rest of the globe. CEPI is now seeking scientifically excellent research and development vaccine development programmes of a nature that will allow the broadest global access of the vaccines that are ultimately developed both within the current pandemic crisis and beyond. This will help curb the current ongoing outbreak, that is resulting in human suffering and a grave global economic crisis. CEPI was set up to respond to the crisis, where our vision is a world in which epidemics are no longer a threat to humanity. Our strategic objectives are further aligned with the sustainable development goals 3, 8 and 17. Of particular importance to CEPI'Äôs work is to ensure that low- and low-middle income countries (LICs and LMICs, respectively) will have access to the vaccines to protect their most vulnerable population, as soon as a vaccine is made available and irrespective of their ability to pay. As the current pandemic has shown, viruses respect no boarders. To successfully curb the COVID-19 pandemic, we must ensure that all countries have the necessary tools to control the outbreak domestically. No-one is safe until everyone is safe.",,2026,COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS,116000000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Norway,,"Vaccines research, development and implementation",,2020 +P23473,101113012,Consolidation of SARS-CoV-2 Genomic Surveillance and Expansion to other Pathogens at RKI,"The COVID-19 pandemic has revealed the importance and absolute necessity of a systematic genomic surveillance of SARS-CoV-2, especially when sequencing data can be combined with clinical and epidemiological datasets. Given this pathogen'Äôs high virulence, rapid evolution and demonstrated capacity for immune escape, there is no question that close and continuous integrated molecular surveillance of SARS-CoV-2 will remain a public health imperative for years to come. Therefore, sustainable infrastructures and efficient processes in the public sector that enable long-term diagnostic and molecular SARS-CoV-2 surveillance are urgently needed. Several of the infrastructure components and processes have been established for SARS-CoV-2 during the first HERA funding phase have a generic character. They can be adapted for the systematic genomic surveillance of other important pathogens, opening up further possibilities to prevent and combat infectious diseases with high public health relevance. Therefore, we propose to address the most relevant topics for enhancing whole genome sequencing (WGS) and reverse transcription polymerase chain reaction (RT-PCR) national infrastructures and capacities, pursuing three specific objectives: 'Ä¢ In the short-term, contribution to the establishment of a sustainable, efficient and high capacity WGS infrastructure and sample/data processes for national public health microbiology; 'Ä¢ In the short/medium-term, contribution to early detection and enhanced monitoring of Influenza A and B virus at the national and the EU/EEA levels; 'Ä¢ In the medium/long-term, contribution to enhanced genomic-based infectious disease outbreak investigation capacities at regional, national and/or EU/EEA levels The proposed actions will have an impact not only at the national and EU levels, but also at the regional level.",,2026,ROBERT KOCH-INSTITUT,2016500,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2023 +P23474,101080692,"Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses","Researchers worldwide have been working to develop a universal flu vaccine, but no breakthrough has yet been achieved. FLUniversal is not ""another costly universal flu project"". It is an opportunity to create a genuine universal flu vaccine that will set the standard for rapid, efficient vaccine development, and generate know-how and tools to develop next-generation vaccines. We plan to exploit our increased understanding of molecular mechanisms of influenza infection and immunity to develop a vaccine effective against all flu virus strains. Our innovation uses genetically modified flu strains administered intranasally in a prime-boost regimen. This approach rapidly induces interferon and broadly cross-neutralising antibodies in the nasal passages and a systemic immune response directed to the conserved HA stalk. Proof of concept for universal protection was demonstrated in the ferret; we propose now to show proof of concept in humans. Previous clinical studies established safety and immunogenicity in humans. The strains are efficiently produced in Vero cells. FLUniversal's objectives align with the Expected Outcomes: comprehensive immunological assessment of preclinical models, development of a human challenge model, and assisting healthcare stakeholders'Äô decision-making about support for vaccine development. Consortium members'Äô world-leading expertise in preclinical models, clinical trials, immunology and validated assays will provide valuable insights on mechanisms of protection. Proposed clinical studies will provide crucial clinical proof of concept to advance the vaccine toward commercialisation.",,2027,Zafiro Business Solutions Korlatolt Felelossegu Tarsasag,8097533.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Hungary,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Vaccine trial design and infrastructure,2023 +P23475,101003562,"Three Rapid Diagnostic tests (Point-of-Care) for COVID-19 CoronaThree Rapid Diagnostic tests (Point-of-Care) for Coronavirus, improving epidemic preparedness, public health and socio-economic benefits","On 30th January 2020 WHO declared a global health emergency for the outbreak of the 2019 novel Coronavirus (COVID-19, or 2019-nCoV) that originated in Wuhan, China. COVID-19 has spread to 27 countries and with 45204 confirmed cases and 1118 deaths (12th Feb 2020), this outbreak exceeds the SARS epidemic in 2002-2003 both in terms of infected and death toll. Diagnostic tests are essential to control the outbreak. The Chinese authorities issued Emergency Use Authorizations (EUA) for 4 new COVID-19 detection products by the end of January 2020 and in the US the FDA issued the first EUA on February 4th. These tests are, however, all based on methods suited only for well-equipped centralized laboratories. CORONADX will provide one 'Äúfront line'Äù and two 'Äúsecond line'Äù diagnostic tools for COVID-19. The 'Äúfront line'Äù diagnostics can be performed as a fast, simple, point of care test (POC) in the field by a minimally trained person (e.g. at hospitals or clinics, at point of entry, in a plane, on a cruise ship, in an ambulance, on a parking lot, in a home quarantine setting etc.). The 'Äúsecond line'Äù diagnostics require minimum (portable) equipment and can be performed by briefly trained personnel in hospitals, primary health care units or in mobile laboratories. These solutions will be available in month 4 and EUA applications will be submitted by month 7. These POCs with lab and field evaluations will allow for fast detection and surveillance of the epeidemic and greatly improve the diagnosis and clinical management of patients infected with COVID-19. The development of rapid POC diagnostics will be supported by clinical and molecular epidemiological studies on the characterization and spatio-temporal evolution of the COVID-19 virus and identify infection sources as e.g. the animal reservoir.The social sciences research in CORONADX will provide information on societal resilience in the era of social media, and the related public health preparedness.",,2023,DANMARKS TEKNISKE UNIVERSITET,3237527.81,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience","Diagnostics | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Communication",2020 +P23476,101046182,"Novel, orally available immune modulator MP1032 with anti-SARS-CoV-2 and anti-cytokine activity","The current global COVID-19 pandemic has caused severe health and socio-economic challenges. Despite significant improvements in the treatment of critical COVID-19 patients and advances in vaccine development, there is still an urgent need for safe and effective early-intervention treatments. To reduce disease burden, hospitalization time, and mortality, it is of critical importance to halt disease progression in early (mild-to-moderate) stages. Our new drug, MP1032, has a dual mode of action, targeting two important mechanisms (immune system overactivation and viral replication) in the early development of COVID-19. Its unique mechanism of self-regulation prevents immune-suppression, which is critical for early intervention. In combination with the oral availability, favourable safety profile, rapid and affordable production scale-up, and potential to work against viral variants, MP1032 is the ideal candidate for early treatment of COVID-19, which can also be used safely in high-risk patients. Therefore, the iMPact project aims to clinically validate MP1032 in a Phase II trial for its ability to stop COVID-19 disease progression. The outcome of the project shall serve as a basis for follow-up rapid Phase IIb/III development and market registration. Four international SME'Äôs will work together in the iMPact project to achieve the objectives: 1) To demonstrate the efficacy of MP-1032 in hospitalized COVID-19 patients, 2) To demonstrate the effect of MP1032 on current SARS-CoV-2 variants, 3) To develop a GMP-compliant production scale-up process for MP1032, 4) To ensure that the clinical development plan is in line with regulatory requirements and 5) To collaborate with existing EU research networks. We have 29 clinical sites on board, and the required expertise for upscaling GMP manufacturing and regulatory preparation is available, ensuring that, by October 2022, MP1032 will be ready to progress to Phase IIb/III trials.",,2023,METRIOPHARM AG,9506581.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2021 +P23477,101024974,Screening of small molecules to fight SARS-CoV-2 by combining novel approaches and sustainability,"The novel SARS-CoV-2 is a lethal human pathogen with no FDA approved vaccines or drugs. An important step of the virus life-cycle is the viral glycoprotein S activation by Proprotein Convertases (PCs) which are proteases with a broad spectrum of cellular substrates. Inhibition of the processing step locks the virus into a form which eventually is no more pathogenic. Therefore, PCs represent attractive drug targets to fight against SARS-CoV-2. To date, there are no PCs inhibitors available for the in vivo use. Here, I propose three approaches to look for small molecule inhibitors of PCs, exploiting the virus cleavage site. Beside the classical in vitro screening, I aim to exploit novel PCs sensor platforms based on innovative ideas to ameliorate and simplify the readout. One attempt will see the use of luciferase reporters on the blueprint of sensors that I have recently published; following a second method, I will take advantage of the cellular death machinery as an on/off cleavage signal. In turn, these virtuous assays will contribute to a sustainable research approach. Novel PCs inhibitors are of great value against Covid-19 infections. Importantly, the inhibitors can be re-purposed against novel emerging pathogens, if necessary. Indeed, PCs dependence is becoming a distinctive mark of severe pathogenicity.",,2024,UNIVERSITA DEGLI STUDI DI PADOVA,311224.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Italy,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P23478,101003673,"Multidisciplinary European network for research, prevention and control of the COVID-19 Pandemic","I-MOVE-COVID-19 aims to obtain epidemiological, clinical and virological information about COVID-19 and patients infected with SARS-CoV-2, through provision of a flexible surveillance platform (adaptable to the epidemiological situation), research studies, hypothesis-testing and evaluation of public health interventions (e.g. vaccination, antivirals) in order to contribute to the knowledge base, guide patient management, and inform the public health response. This will be achieved through adaptation and expansion of the existing, long-running, Europe-wide influenza surveillance network (I-MOVE) to include COVID-19. The network includes primary care networks, hospitals, national laboratory reference centres in ten countries. I-MOVE-COVID-19 priority activities and research projects will be selected based on ECDC/WHO input and the proposal'Äôs detailed list. These will be conducted by mobilising an existing large European multidisciplinary network, combining the expertise and resources of groups working in surveillance (epidemiological, clinical, virological), respiratory disease research, and evaluation of vaccines/treatments. Through protocol sharing and pooling European results, questions will be answered which could not be efficiently answered by countries acting alone. I-MOVE-COVID-19 will share study results rapidly and widely with national and international partners and with the wider scientific community and contribute to clinical management of patients and public health preparedness and response to COVID-19.",,2022,EPICONCEPT,3145142.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,France,,Epidemiological studies,Disease surveillance & mapping,2020 +P23479,101046118,RBD Dimer recombinant protein vaccine against SARSCoV2,"The main objective of RBDCOV project is to test the efficacy, tolerability, and safety of two new vaccines against different variants of COVID-19 (Wuhan and South African/UK) based on the outstanding data generated using a recombinant protein developed by the consortium partners. Two different phase I/II clinical trials will be run during the project duration: Phase I/II for paediatric population to analyse the Wuhan vaccine and Phase I/II in adults to analyse adjuvanted recombinant RBD protein codifying for SA and UK SARS-Cov-2 variants given as a booster vaccination. The aim of the project is to focus not only on the current SARS-CoV-2 variants but also in the emerging ones as United Kingdom and South African variants. Thus, a continuous monitoring of the new emerging variants will be performed throughout the project to ensure that the platform is prepared to cope with the disease. The platform used for the generation of the vaccines is adaptable to variants and will be ready to include in the design any other potential variant that could appear in short, medium and large term as the recently identified Indian one. Preclinical data are already available as described in the proposal. The core of RBDCOV consortium has been in close contact to the corresponding agencies and considering Reflection paper on the regulatory requirements for vaccines intended to provide protection against variant strain(s) of SARS-CoV-2, preclinical data supporting the first vaccine candidate can be extrapolated for the vaccines against the new emerging variants. This create a unique opportunity for RBDCOV consortium to generate the first RBD recombinant vaccine to be approved in Europe. This vaccine will be manufactured by an European technological company that will change actual paradigms and allow the really change to One health concept, based on the close relationship between the animal world and the onset of certain infections in humans.",,2024,HIPRA SCIENTIFIC SL,11050508.43,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2021 +P23480,101003666,Rapid therapy development through Open nCoronavirus Vaccine Platform,"The OPENCORONA consortia will test a therapy that protects against 2019-nCoV infection and/or disease in a phase I clinical trial in 24 months. The spread of the 2019-nCoV (or SARS-CoV-2) between the Jan 21 and Feb 11 has expanded alarmingly. There are >43000 confirmed cases of which >1000 has died. Around 7000 have a severe disease. The infection still mainly affect mainland China, although an increasing number of cases are seen outside China. The major question is what will happen when China halts its massive isolation campaign. No approved human coronavirus immunotherapy or vaccine exists. Thus, speed in therapy and vaccine development is critical. Genetic analysis shows that the 2019-nCoV envelope and receptor binding domain only has a 75% homology with other human coronaviruses. Thus, existing immunotherapies and vaccine candidates against other coronaviruses, such as SARS, will not be useful against 2019-nCoV. We will use the DNA vaccine platform as this is currently the most rapid and robust vaccine platform today. We will generate chimeric 2019-nCoV genes (Figure 1) and select the most potent DNA vaccine/immunotherapy candidate delivered by in vivo electroporation that protects against 2019-nCoV infection and/or disease in animal models and take this to phase I clinical testing. The partners in the consortium have done this before and all know-how for reliable development is present. KI and FoHM will develop vaccine candidates and infectious models, JLU will test candidates for over-activation of innate immunity, IGEA will provide a CE marked device for in vivo electroporation in humans. Cobra will produce plasmid according to GMP, Adlego will perform toxicological testing according to GLP, and Karolinska will write the (Investigator'Äôs brochure) and IMPD (Investigational Medicinal Products Dossier), file with ethics comitty and EMA, and perform a phase I clinical trial of the immunotherapy/vaccine in healthy volunteers. All these tasks are within the expertise that the partners do every day. Thus, this is truly realistic.",,2024,KAROLINSKA INSTITUTET,3270000,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Sweden,,"Vaccines research, development and implementation",Pre-clinical studies | Phase 1 clinical trial,2020 +P23481,101113133,Consolidation of WGS and/or RT-PCR national infrastructures and capacities within Ireland to respond to the COVID-19 pandemic and future health threats,"In January 2021, the Chief Medical Officer / Chair, National Public Health Emergency Team (NPHET) requested the HSE to develop a proposal for SARS-CoV-2 Whole Genome Sequencing (WGS) Surveillance Programme in Ireland. An expert Working Group, informed by international guidance developed a proposal to design and establish a suitable programme. This was presented to NPHET and approved for implementation. A Steering Group was established to oversee design & implementation of this SARS-CoV-2 WGS Surveillance Programme (the Programme). A regional hub and spoke model, incorporating 6 regional hospital laboratories (spoke labs) and a central National Virus Reference Laboratory (NVRL hub), along with HPSC (National Surveillance Centre). A 7th lab in CHI-Crumlin, national paediatric hospital joined in 2022) was established in Q4 2021. This model aligns with a concurrent Public Health Reform Programme in which there are six Regional Health Areas (regions). The Programme was launched in Q4 2021. The overarching aim of the Programme in phase 1 was to track the molecular epidemiology of SARS-CoV-2 in Ireland to inform and enhance the urgent public health response to the COVID-19 pandemic through; 'Ä¢ National surveillance of variants (community & hospital) 'Ä¢ Early detection of variants of concern 'Ä¢ Complex outbreak investigation 'Ä¢ Vaccine escape/ reinfection investigation 'Ä¢ Unexpected change in transmissibility/ virulence investigation 'Ä¢ Antiviral resistance investigation 'Ä¢ Human-animal transmission investigation 'Ä¢ Monitoring immunocompromised patients undergoing antibody therapy 'Ä¢ Investigating unexpected changes in diagnostic performance 'Ä¢ Monitoring emerging lineages in animals The next phase of the Programme aims to make the Programme sustainable, expand WGS and molecular surveillance to other pathogens, develop more advanced data visualisation and generic workflow processes., develop clinical bio-informatic capacity in the Irish Health service and upskill Scientists an",,2027,HEALTH SERVICE EXECUTIVE HSE,1803324.34,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,Epidemiological studies,Disease surveillance & mapping,2023 +P23482,101046041,EU-Africa Concerted Action on SAR-CoV-2 Virus Variant and Immunological Surveillance,"Despite of the successful advances achieved to date in the fight against the COVID-19 pandemic with the development of vaccines and therapy, the worldwide propagation of SARS-CoV-2 has resulted in the rapid evolution of this virus and in the emergence of variants of concern (VOC) that may dampen the efficacy of the first generation vaccines. To tackle the challenges associated with the VOC, the CoVICIS program is proposing a global approach with a powerful state-of-the-art virologic and immunologic platforms coupled with large genomic surveillance studies and diverse cohorts in EU and SSA. This allows CoVICIS to contribute to the early identification of emerging VOC and address key unanswered questions regarding i) the susceptibility to infection with VOC after a prior infection in the setting of a long-COVID or after vaccination with different vaccines, ii) the risk posed by VOC in immunocompromised patients, and iii) the modalities of infection and immune responses in children. The diversity of the cohorts provides a unique opportunity to study virus evolution in different settings, where SARS-CoV-2-specific humoral and cellular immune responses are predicted to vary very significantly. Beyond the genomic surveillance, the ground-breaking research and innovation of the program is the characterization of virologic and immunologic properties of VOC and the identification of immune correlates of protection after disease or vaccination. CoVICIS'Äô ambitious goals are only achievable thanks to the existing population studies and cohorts funded by national and international public agencies and public-private partnerships, and the combined collective expertise of CoVICIS partners in the fields of epidemiology, genomics, virology, immunology, data science and public health.",,2024,CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS,11656806.36,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Characterisation of vaccine-induced immunity",2021 +P23483,101058751,"DEVELOPMENT OF ANTIMICROBIAL, ANTIVIRAL, AND ANTIFUNGAL NANOCOATINGS FOR EVERYDAY SURFACES","Since the end of 2019, the spread of COVID has deeply changed our lifestyle, resulting in historical events and decisions, such as the EU block of non-essential travel among countries (COMM (2020) 499), affecting the whole EU society economically and psychologically. However, as reported in the HERA target priorities, the persistence of the emergency status requires daily actions that tackle the spread of COVID. In this economical, societal and clinical context, the project MIRIA aims to develop wide-range-antimicrobial nanocoatings to be used in hospitals and other environments where cross-contamination and contagion risk are significant issues. In the wake of the covid outbreak, there has been large concern about infection spread of pathogens (i.e., bacteria, fungi, virus, and specifically SARS-CoV-2) via high traffic surfaces (i.e., medical equipment). State of the art and commercial products coating solutions that both target a range of mixed pathogens and different surfaces (e.g., glass, metal, textile) are unfortunately scant. MIRIA solutions aim to fill this void, impacting on EU health, both directly (by creating public safe environments) and indirectly (by reducing COVID spreading and decreasing ill-related work absences and psychological pathologies). A reduction of the work absence of at least 5% with respect to the 2020 value (15M in EU) is expected. MIRIA main challenging ambition is to develop nanocoatings with a 99.99% effectiveness against a wide range of pathogens, especially SARS-CoV-2. This will be based on a four pieces puzzle: the knowledge in anti-microbial materials, nanopowders, nanocoating and pilot plant conduction. These nanocoatings will be brought to pilot scale (TRL6) and, within 3 years after the end of the project, they are foreseen to enter the market (TRL9). The exploitation of MIRIA outputs deeply involves SMEs and the dissemination plan will follow a spill-over strategy in order to involve public and private stakeholders.",,2026,RINA CONSULTING - CENTRO SVILUPPO MATERIALI SPA,6255066.99,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Disease X | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Italy,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P23484,101037867,VACCELERATE - European Corona Vaccine Trial Accelerator Platform,"The ongoing COVID-19 pandemic creates an unprecedented burden worldwide. Vaccine-induced immunity is the only promising solution. There is continued need for phase 2 & 3 vaccine trials to reach long-term, large-scale immunity of the entire European population. VACCELERATE will be the pan-European backbone accelerating phase 2 & 3 COVID-19 vaccine trials. The overall objective of VACCELERATE is to connect all European stakeholders involved in vaccine development to provide a pan-European platform for clinical trial design and conduct. VACCELERATE constitutes the rapid response single entry-point to stakeholders from public health authorities to vaccine developers, to address respective needs and kick-start specifically phase 2 & 3 vaccine trials. VACCELERATE conducts capacity mapping of clinical trial and laboratory sites to identify suitable sites for individual phase 2 & 3 vaccine trials. Capacity building via training will increase quality in sites across Europe. Volunteer registries facilitate patient recruitment. Access to laboratory sites and a standardised set of assays essential for clinical phase 2 & 3 trials is provided. A harmonised European approach to vaccine trials is enabled by aligning educational standards, coordination of laboratory support and providing standardised assays and trial protocols. Harmonised data collection, open data sharing and pooling of data for stronger analysis enables data standardisation. VACCELERATE offers solutions for characteristic vaccine development issues during pandemics by closing gaps in public health knowledge and improving knowledge transfer. VACCELERATE amalgamates the vast but scattered expertise across Europe into one network to deliver strategic scientific leadership and guidance on vaccine trials in Europe. Beyond the COVID-19 pandemic, it will be an established pandemic preparedness network, ready to face emerging future pandemics, as well as a pivot in Europe?s capacity to develop vaccines.",,2024,KLINIKUM DER UNIVERSITAET ZU KOELN,32064762.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Physicians,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,"Vaccines research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial | Vaccine trial design and infrastructure,2021 +P23485,101081838,Virus Inhibition by siRNA Optimized by NMR,"The last two years, profoundly marked by the COVID-19 sanitary crisis, have demonstrated the difficulties to answer adequately to the emergence of novel pathogenic viruses. Today, no broad-spectrum antiviral exists similar to antibiotics targeting bacteria. Repositioning of existing molecules had limited success despite intense initial hopes. Vaccines have played a major role in fighting the pandemic and limiting the impact of the virus, however it remains insufficient to end the pandemic, due to many factors including their worldwide uneven accessibility, their intrinsic efficiency towards different variants and the complex socio-political context related to mass vaccination. There is therefore an urgent need of novel approaches to design molecules targeting viruses and in particular SARS-CoV-2. To answer this challenge, we propose a novel strategy derived from fundamental research on small interfering RNA (siRNA). This project derives from the ERC Starting Grant PARAMIR, in which novel structural biology approaches are proposed to understand the mechanism of recognition of a similar class of RNA involved in numerous diseases, especially cancer. Our approach combines the latest advances in SARS-CoV-2 virology and structural biology to propose efficient and specific molecules active towards a broad range of SARS-CoV-2 current and future variants. If successful the project will lead to a class of siRNA, with optimized specificity and stability, validated in vitro and ex-vivo in a reconstituted human airway epithelial model, and ready for testing towards pre-clinical and clinical stage. Finally, the strategy proposed here will be on a longer term applicable to multiple other pathogenic viruses.",,2024,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,150000,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P23487,101015930,Intelligent plug-and-play digital tool for real-time surveillance of COVID-19 patients and smart decision-making in Intensive Care Units,"Within only six months, over 7.4 million people have been diagnosed with SARS-CoV-2. In the most severely hit countries, more than 10% of infected patients have received treatment in Intensive Care Units (ICUs). Insufficient data and limited knowledge on the disease as well as the lack of tools to support the intensivist in making accurate, timely and informed decisions has led to high mortality rates. Continuous surveillance, the collection and intelligent analysis of data from many sources, including ventilators and electrical impedance tomography, would allow intensivists to decide on the best suitable treatment to accelerate the recovery of the often comorbid COVID-19 patients, while reducing the burden on clinical staff and healthcare costs. This information would also increase our understanding of the yet unknown course of disease, supporting other stakeholders in the quest for new therapies. In ENVISION, our multidsciplinary public-private consortium will advance an innovative digital tool, Sandman.MD, a real-time and plug-and-play monitoring app, to an intelligent decision-support system for monitoring, prediction and treatment of COVID-19 patients in ICUs 'Äì the Sandman.ICU 'Äì reaching Technology Readiness Level 9 and ready for CE marking by the end of the project. The app has been developed by our SME partner app@work and successfully introduced by several hospitals in Germany for use during the perioperative period. Sandman.ICU will be integrated into an AI-driven data analytics suite with predictive modelling tools and enhanced with a smart alert functionality. The digital tool will be validated and demonstrated in 14 hospitals across Europe. Our Health Technology Assessment expert partner will demonstrate the economic and societal value of Sandman.ICU, while an experienced SME will manage the innovation process in view of an immediate market uptake. The rollout will be supported by the European Society of Anaesthesiology and Intensive Care.",,2023,JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN,5848933.2,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23488,101016233,Pan-European Response to the ImpactS of COVID-19 and future Pandemics and Epidemics,"The impact of the COVID-19 pandemic has been deep and wide. In spite of unprecedented efforts to understand the COVID-19 disease and its causative virus SARS-CoV-2, months after the emergence of the first local case in Europe (San Matteo hospital, Pavia, 21st February 2020) significant knowledge gaps persist. While social and natural scientists managed to develop new research and shed light on the dynamics of the outbreak and the most effective possible containment measures, governments have been increasingly faced with the need to adopt urgent decisions. Against this background, PERISCOPE plans to contribute to a dramatically deeper understanding of the dynamics of the outbreak, by means of an intense multi-disciplinary research, both theoretical and experimental, and the consideration of different viewpoints: clinic and epidemiologic; humanistic and psychologic; socio-economic and political; statistical and technological. The overarching objectives of PERISCOPE are to map and analyse the unintended impacts of the COVID-19 outbreak; develop solutions and guidance for policymakers and health authorities on how to mitigate the impact of the outbreak; enhance Europe'Äôs preparedness for future similar events; and reflect on the future multi-level governance in the health as well as other domains affected by the outbreak. In pursuing this objective, PERISCOPE sheds new light on the unintended and indirect consequences of the outbreak and the related government responses, with the intention to preserve evidence-based policymaking by collecting an unprecedented amount of data and information on the social, economic and behavioural consequences of the current pandemic. At the same time, PERISCOPE will produce new information on the conditions that led to the impact of the pandemic, the differences in 'Äúpolicy mix'Äù adopted at the national level in EU and associated countries, and the behavioural impacts of both the outbreak and the policies adopted.",,2023,UNIVERSITA DEGLI STUDI DI PAVIA,11692365.75,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Other secondary impacts | Health leadership and governance,2020 +P23489,101113221,Consolidation of the HERA-WGS-infrastructure and capacity building at NIPH to enhance microbial surveillance and preparedness,"The Norwegian Institute of Public Health (NIPH) is the national infection control institute in Norway and is the national reference laboratory for a total of 30 bacteria and viruses. Microbial surveillance is an essential part of the NIPH laboratory activity. The role as reference laboratory covers research, laboratory-based surveillance and characterization of pathogens, outbreak investigations and response, as well as specialized microbiological assays. We received in 2021/2022 a grant from HERA for enhancement of whole genome sequencing (WGS) infrastructure and capacity at our institute, with COVID-19 response as the main aim. Within the HERA-financed project, we have focused on laboratory automation and digitalization. In particular, we have purchased pipetting robots and barcoding system, and we have worked with integration of laboratory instrumentation in the SARS-CoV-2 WGS workflow with our laboratory information management system (LIMS). In addition, we have further developed our LIMS to serve as a database for all laboratory results for more efficient downstream sequence analysis. We now aim at consolidating the achieved deliverables from the HERA grant on SARS-CoV-2. The general objective of this project is therefore to further strengthen and expand our microbial WGS as well as other genomic based analyses. We will do this by digitalisation of data handling and automation of our laboratory workflow, including digitalisation of instrument data, expanding the current WGS activity to several pathogens, develop downstream visualisation and reporting platforms, and streamline the related processes. This will allow us to enhance microbial surveillance, more rapidly and efficiently respond to the Covid-19 pandemic, as well as enhance our preparedness for future pathogens and other cross-border threats.",,2025,FOLKEHELSEINSTITUTTET,1600500,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Norway,,"Epidemiological studies | Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P23490,101046016,European Cohorts of Patients and Schools to Advance Response to Epidemics,"The EuCARE project gathers a comprehensive multidisciplinary team of clinicians, virologists, epidemiologists, statisticians and top experts in artificial intelligence to unveil the impact of SARS-CoV-2 variants on key sectors of public health, as addressed by the call. The specific activities include: 1. The assessment of natural and artificial immunity to the different viral variants in health care workers with the aim of defining the cross-immunization patterns and the risk of vaccine escape, informing vaccination strategies for the general population; 2. The analysis of the clinical course and long-term follow-up of hospitalized COVID-19 patients to derive the role of different viral variants in the outcome of the infection, including post-acute sequelae of SARS-CoV-2 infection; 3. The definition of the best strategies to control the spread of different viral variants in schools, by comparing the outcome of diverse containment and prevention measures in relation to the prevalence and dynamics of the variants. To ensure a suitable representativeness of the different variants, vaccines and preventive measures, EuCARE has secured the appropriate cohorts from diverse geographic areas including European countries, Kenya, Mexico, Russia and Vietnam, and will consolidate or expand interactions with other cohorts. To deal with complex interactions among many variables, including large dimensional parameters, EuCARE harnesses the power of artificial intelligence to define the role of viral variants and inform clinical guidelines and prevention measures. In the longer-term, EuCARE is committed to maintain active cooperation beyond the duration of the project with a dedicated task in the project. The solid IT and ethics infrastructure and the harmonised research procedures will make the cohort and laboratory network rapidly available to tackle newly emerging infectious diseases, thus contributing to pandemic preparedness on a global scale.",,2026,EURESIST NETWORK GEIE,11595267.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Impact/ effectiveness of control measures | Supportive care, processes of care and management | Post acute and long term health consequences | Characterisation of vaccine-induced immunity",2021 +P23492,101057553,Decision support for prediction and management of Long Covid Syndrome (LCS),"We will develop tools and knowledge to support physicians in accurately managing Long COVID syndrome (LCS) which has a significant impact on sufferers as well as their surroundings. Although much is now known regarding appropriate clinical management of acute COVID-19, very little is known about clinical manifestations, risk factors and underlying mechanisms for development of the highly heterogenous LCS. In this project, we aim to understand and mechanisms of LCS by combining front-line expertise from the fields of clinical medicine, virology, metabolism and immunology. We will study the pathogenesis of LCS by conducting geographically diverse cohort and registry studies, by conducting mechanistic studies, by using novel high-throughput methods for biomarker analysis, and by conducting interventional and follow-up studies on LCS patients. We will combine results from clinical and mechanistic studies to identify molecular and physiological parameters and/or pathways to decipher the mechanisms underlying LCS. We will exploit the high-throughput omics technologies to identify the predisposing factors and biomarkers that lead to the development of LCS. We will collect data from the cohort, mechanistic, biomarker and interventional studies and use these to validate the predictive artificial intelligence algorithms and to produce information and gain understanding on the combination of factors that lead to certain clustering of patients into different groups with specific symptoms. A machine learning and AI-informed Long Covid Prediction Support (LCPS) tool will be developed for the use of clinicians to predict the LCS and its possible clinical manifestations in patients. It will also help in the choice of personalized treatments for LCS patients. Additionally, an interactive graphic user interface infographic will also be available to clinicians and patients; this will communicate novel and understandable information about LCS and recommendations for patient management.",,2026,HUS-YHTYMA,7008151.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Finland,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2022 +P23493,101005142,"Development of Impentri, an intravenous imatinib formulation for Covid-19 acute respiratory distress syndrome (ARDS).","The accumulation of fluid in the lungs is a significant feature of the pathology in patients with severe Covid-19 infection. This build up of fluid, contributes to difficulty in breathing and in some cases death. This fluid in the lungs results in part from direct damage to cilia and mucus cells and resulting debris and in part due to plasma extravasation triggered by the immune response to infection and associated damage. Imatinib, a generic marketed drug has been shown to reduce plasma extravasation following inflammatory challenge in animal models and this effect is supported by anecdotal observations in the clinic. This project proposes to rapidly implement a multi-center, randomized, open label, double-blind, Phase IIb study to evaluate the efficacy, safety and pharmacokinetics of imatinib mesilate in patients with corona-virus associated pneumonitis. 100 patients entering ICU with a diagnosis of corona-virus associated pneumonitis will be randomised, half receiving i.v. imatinob , 200mg bid for 5 days and one half placebo. Adverse events, immunological parameters and imatinib pharmacokineticswill be monitored. Outcome measures Primary: PaO2/FiO2 ratio. Secondary: rate of intubation/need for mechanical ventilation, pulmonary edema on high resolution CT, Oxygenation Index, respiratory mechanics, duration of mechanical ventilation, fluid balance, ICU length of stay, mortality. This project has already received EMA scientific advice for the treatment of acute respirator y distress syndrome and has granted orphan drug status.",,2022,EXVASTAT LTD,4102518.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,United Kingdom,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2020 +P23494,101095619,Efficient and rapidly SCAlable EU-wide evidence-driven Pandemic response plans through dynamic Epidemic data assimilation,"Pandemics have the potential to disrupt our daily lives and to affect every part of society. SARS-CoV-2 causing COVID-19 disease painfully showed how responding too late, in a fragmented mannar and/or with too little coordination across different sectors and countries, led to huge human and economic costs. ESCAPE'Äôs main objective is to improve efficiency and scalability of early pandemic response plans by providing evidence-based guidelines, standardised research protocols, retrospective insights, and digital solutions that will support scientists in producing and integrating evidence and inform public health authorities in taking decisions to avert or reduce disease and societal burden. The project will provide knowledge and tools that will enhance Europe'Äôs preparedness for a pandemic of pathogen X. These include a science-based blueprint for faster and better decision-making in managing pandemics, tools and frameworks to improve data availability, collection and sharing, as well as advanced analytics and models to understand and project transmission dynamics of pathogen X under candidate response scenarios. ESCAPE will also identify determinants of success and failure in managing pathogen X based on the SARS-CoV-2 pandemic, helping to develop effective response strategies for future pandemics. In addition, the project will contribute to fostering a multi-stakeholder intelligent community allowing improved knowledge sharing and cooperation between policy-makers, the scientific community, the media and the public, ensuring a much more effective response to future pandemics. In the long-term, by improving pandemic preparedness and the effectiveness of response to a pandemic of pathogen X, the project will contribute to reducing health burden and potential negative societal and economic consequences during pandemics, as well as increase the confidence of policy makers and the public in science-based solutions.",,2026,UNIVERSITEIT HASSELT,2590395.1,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,,,2023 +P23495,101113174,Sequencing pathogens for Epidemiology,"The French EMERGEN Consortium was created in 2021 to scale up SARS-CoV-2 genomic surveillance and research. Coordinated by Sant√© publique France and ANRS|Maladies Infectieuses Emergentes, it is based on a network of public and private laboratories, including the National Reference Laboratory (NRL) for respiratory viruses, and a centralised database. Our priority in 2021 was to build the infrastructure and network, in a time of crisis with a huge pressure for results; more than 300 000 SARS-CoV-2 sequences were produced and analysed, a 100-fold increase when compared to 2020. In 2022, the ECDC/HERA grant was used to achieve new objectives: sequencing data quality, capacities in overseas territories, network animation, and timeliness of sequencing. These activities helped in better detecting and assessing new variants, from Delta to Omicron and its sublineages, and are still increasing; the 600 000 sequences milestone was reached in June 2022. EMERGEN was built as a first stage of a sequencing network for emerging pathogens, complementing NRL capacities, and its scope will expand to other respiratory viruses as a component of a new acute respiratory infections surveillance scheme. In addition to national funding, the EU4Health grant will help consolidating WGS activities in 2023/2024 to ensure the sustainable use and integration of EMERGEN into routine surveillance and investigation activities. We defined two objectives focusing on data use and valorisation. The first objective is to implement methods to better monitor viral epidemics, ensure the accurate detection of variants of interest (in the context of international efforts) and use molecular data to monitor within-outbreak pathogen dynamics using phylodynamics and to investigate clusters. The second objective is to continue efforts for integrating genomic and epidemiological data at regional level for investigations and animating lab networks, with an emphasis on French overseas territories.",,2025,AGENCE NATIONALE DE SANTE PUBLIQUE,1374734.44,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P23496,101054460,Circular RNAs to reverse pathological remodelling of the injured heart,"Heart failure (HF) is a most common cause of mortality with currently >60 million of affected patients. Numbers will increase due to socioeconomic factors and as a result of the current COVID-19 pandemic. A major underlying cause of HF are cardiac remodelling processes at the molecular, cellular and tissue level. We will here focus on noncoding circular RNAs (circRNA) involved in two distinct forms of cardiac injury, chemotherapy-induced cardiotoxicity and SARS-CoV-2-infection, where currently no specific treatment strategies are available to reverse disease pathology. First proof-of-concept studies targeting the cardiac remodelling process by noncoding RNA modulation have been pioneered by us and were recently tested in a world-wide first clinical phase 1b study in HF patients. Within the family of non-coding RNAs, circRNAs are stable and species-conserved and thus ideal drug targets. We discovered multiple molecular circRNA signatures during remodelling of cardiac cells and tissues from mice and patients. We now aim to lift our research to its next inflection point with the following steps and interconnected objectives: a) discover key functional circular RNAs involved in remodelling processes by functional CRISPR-Cas library screening; b) validate circRNAs by manipulating human living beating myocardial tissue, c) explore their mode of action; and d) perform targeted cardiac delivery approaches of selected candidates in both chemotherapy-induced cardiotoxicity and SARS-CoV-2-induced cardiac disease models. A combination of bioinformatic, molecular and physiology-based methods, unique established noncoding RNA drug discovery pipelines, availability of modern S3-safety labs, large clinical biobanks and (fresh) human cardiac tissue for slicing preparations form the basis for a successful strategy. REVERSE aims to discover fundamentally new therapeutic entry points for two forms of cardiac injuries, where currently no disease-specific treatments are available.",,2027,MEDIZINISCHE HOCHSCHULE HANNOVER,2424393.75,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Post acute and long term health consequences",2022 +P23497,101023196,Restriction of HIV and coronavirus infections by the innate immunity protein Shiftless,"Programmed ribosomal frameshifting (PRF) is a mechanism of recoding that allows synthesis of multiple proteins from the same mRNA by shifting the translation reading frame. Many viruses, including medically important HIV and coronaviruses rely on PRF to increase their coding capacity and modulate appropriate stoichiometric ratios of viral proteins. An interferon-inducible restriction factor Shiftless (SFL) can block the frameshifting required for viral translation and infectivity. Understanding the mechanism of action of SFL will undoubtedly guide the design of new antiviral therapeutics. However, most structural and functional aspects of SFL and its role in viral infections are unknown. We intend to characterise the role of SFL in HIV and coronavirus infections using a three-pronged approach: (i) We will elucidate the mechanism of inhibition of PRF on viral mRNAs by SFL using a state-of-the-art in vitro reconstituted translation system and depletion/deletion of SFL in human cell lines. (ii) We will determine the interaction of SFL, translating ribosome and frameshifting viral mRNAs using cryo-electron microscopy. (iii) Based on the structural data obtained, we will generate mutants of SFL and characterise their activities by in vitro and cellular translation assays to identify specific domains and amino acid residues required for the antiviral activity of SFL. The results expected from our proposed study should not only be crucial for understanding the molecular mechanism of SFL but should also provide vital inputs to the development of antiviral therapeutic agents by either mimicking or upregulating SFL expression against critically important viruses such as HIV and SARS-CoV-2. Importantly, our research should continue to be relevant for the treatment of any future frameshifting virus.",,2023,MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV,211515.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P23498,101113063,Consolidation of national eHealth infrastructure for combined genomic-epidemiologic surveillance of infectious diseases,"In response to the COVID-19 pandemic, the European Commission established the European Health Emergency Preparedness and Response Authority (HERA). It strengthens the European Health Union with better preparedness and response to future national, cross-border or pandemic outbreaks of infectious disease. The HERA-Incubator-2021 project was launched by HERA, and its implementation in Belgium makes it possible to develop a national infrastructure for the collection of Whole Genome Sequencing (WGS) data and to build a sustainable infrastructure in which genomic data can be linked to clinical and epidemiological data. This can be used more broadly to anticipate outbreaks and manage risks. The project aims to process larger data volumes in case of major outbreaks or a pandemic. The HERA-Incubator-2021 action was set up as a proof-of-principle. A design of the structure and processes for the clinical, microbiological and genomic data transition was obtained through facilitation of healthdata.be. A central BioIT platform, connected to the data collection, will provide automated pipelines for autonomic processing of genomic data, which will allow harmonised pathogen analyses. Five pilot national reference centers (NRCs) for human microbiology will demonstrate the transition towards the national eHealth infrastructure. With this project proposal developments of the previous action will be consolidated and further expanded. The focus will lie on enhancing base functionalities, i.e. data input/output platform, central BioIT platform, central NRC platform, and roll-out to other participants, i.e. more laboratories and pathogens. Additionally, a strong investment will be made on the communication and dissemination of the project and its objectives. We aim to highlight the future possibilities of the national eHealth infrastructure for public health response in relation to genomics-based infectious disease outbreak investigations, surveillance and overall pandemic preparedness.",,2024,SCIENSANO,1904109.94,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing | Digital Health,,,Belgium,,Epidemiological studies | Health Systems Research | Research on Capacity Strengthening,Disease surveillance & mapping | Health information systems | Cross-cutting,2023 +P23499,101137148,Long-term alterations of host-microbiome interactions and cardiovascular and respiratory diseases progression after pneumonia,"Challenges. The incidence of cardiovascular diseases (CVD) increases after infections, but causal mechanisms are not understood yet. Pneumonia, which can be acquired in the community (such as flu and COVID-19) or during hospitalization, is a leading cause of infectious diseases. The main idea of the Homi-lung project is to investigate the causal relationship between CVD progression and the immune and microbiome alterations observed after pneumonia. Objectives. During the Homi-lung project, we aim to i) define the medical and societal, and patient needs; ii) increase medical doctor'Äôs knowledge of the physiological processes linking pneumonia and CVD; iii) enable early identification of patients at risk of CVD progression; and iv) preclinically develop new treatments. Implementation. The Homi-lung project will address this challenge by comparing CVD rates between patients cured of pneumonia and matched patients who had not developed pneumonia during a prospective 3-year follow-up. We will analyze longitudinal samples collected in these populations and develop new algorithms by artificial intelligence to associate host-microbiome interactions with CVD progression. We will also demonstrate the causal link between CVD progression and host-microbiome interactions in preclinical pneumonia models. The interdisciplinary and ambitious Homi-lung project brings together 8 partners from 5 EU countries, with expertise in pneumonia, CVD, immunology, microbiome, and artificial intelligence and is uniquely placed to reach these objectives. Impacts. The project will provide clinicians with robust evidence contributing to identifying patients at risk of CVD after pneumonia. By developing new biomarkers and preclinical validating treatments to TRL4, the project will contribute to improving patients'Äô recovery and reducing the burden of infections. This project, particularly timely after the COVID-19 pandemic crisis, will also increase European preparedness for the next pandemic.",,2028,NANTES UNIVERSITE,15399963.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae | Unspecified,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2024 +P23500,101080528,INNOVATIVE NASAL VACCINES TO PREVENT PATHOGEN COLONIZATION AND INFECTION IN THE UPPER RESPIRATORY TRACT,"Bacterial and viral respiratory infections are a leading cause of morbidity and mortality worldwide. Streptococcus pneumoniae and Bordetella pertussis, influenza virus and SARS-CoV-2, are responsible for diseases with major public health impact: community-acquired pneumonia, whooping cough, influenza and COVID-19, respectively. Vaccines against some of these diseases, administered by intramuscular or subcutaneous injection, do not prevent colonization or infection of the upper respiratory tract (URT), and therefore have limited impact on pathogen transmission. The NOSEVAC consortium aims to develop and assess innovative nasal vaccine platforms as a novel concept to block the earliest stage of infection, thereby inhibiting URT colonisation, transmission and disease. The project builds on a unique consortium of 12 renowned and complementary teams from the EU, UK and Switzerland. NOSEVAC'Äôs objectives are to: 'Ä¢ Develop vaccine formulations for nasal delivery of RNA- and protein-based antigens 'Ä¢ Discover bacterial antigens that promote colonization of the URT 'Ä¢ Use a combination of in vitro and in vivo models for optimal evaluation of vaccines efficacy 'Ä¢ Identify key host immune factors required for long-term protection of the URT in human 'Ä¢ Deliver two nasal vaccine candidates to fight S. pneumoniae and B. pertussis infection, and a single bivalent vaccine to prevent influenza and COVID-19 'Ä¢ Address acceptability of nasal vaccination Expected outcomes include (1) strengthening innovation in Europe by enriching the pipeline for novel vaccines against (new) respiratory infections, (2) increasing knowledge on the mechanisms underlying URT colonization, infection and immunity, and (3) evaluating nasal vaccine acceptability by stakeholders. NOSEVAC will develop strategic research avenues to fight respiratory pathogens including those with epidemic potential and will facilitate evidence-based decision making to policy makers and investors.",,2028,EUROPEAN VACCINE INITIATIVE E.V,7501393.9,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Germany,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P23501,101041484,Tracing virus-specific CD8+ T cell clonotype zonation and function in humans,"The current Covid-19 pandemic highlights the need to gain better understanding of precise mechanisms that enable immune control of viral infections. Although it is established that CD8+ T cells are required to suppress viremia, most view these cells simply as ?killer T cells? based almost exclusively on studies of blood. I recently discovered that efficient immune control of HIV is mediated primarily by non-killer resident memory CD8+ T cells, whereas CD8+ T cells with high ?killer instinct? are mainly confined to the vasculature. These observations force a reevaluation of how antiviral CD8+ T cells are distributed anatomically and function in the tissue spaces where most viruses replicate. Using cutting-edge single-cell technologies on unique paired tissue samples from human organ donors, my aim here is to challenge prevailing concepts in the field of adaptive immunology and reassess how and where CD8+ T cells actually target viruses in the human body. My group will first use single-cell barcoding techniques to establish a reference map of CD8+ T cell clones specific for multiple viruses across tissue sites. We will then dissect this information to determine whether distinct resident memory CD8+ T cell clones and/or subsets exhibit differential antiviral functions across tissue sites. In parallel, we will use more mechanistic approaches to define the epigenetic imprints and functional properties of antiviral CD8+ T cells, aiming to determine to what extent these features are shaped by subset fate, anatomical location, and/or the nature of the expressed T cell receptor. A specific emphasis throughout this project will be to translate the emerging knowledge to the field of Covid-19, aiming to understand how CD8+ T cells control SARS-CoV-2. This ambitious but technically feasible project will establish a systematic foundation for future studies of antiviral T cells in humans and inform the development of more effective vaccine platforms to combat future viral threats.",,2027,KAROLINSKA INSTITUTET,1604927.24,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P23502,962483,Mass Casualty Ventilation Monitoring,"The viral pandemic we are facing (COVID-19) has pointed out that in the wake of a virulent flu strain, patients with survivable illness will die from lack of resources unless more ventilators are made available. Hospitals have almost no reserve ventilators to respond to disaster or pandemic. Critical-care ventilators are complex and their high cost makes it impossible to stockpile them, so simple, low-cost, ventilators are the only suitable solution at the moment. Because of their technical simplicity, the performance of such ventilator is highly impacted by patient'Äôs pulmonary characteristics which could cause either hypoventilation or hyperventilation resulting in severe lung injuries and death. The important difference between these disaster ventilators and advanced emergency ventilators is the absence of alarms for undesirable events (disconnection, ventilation failure, O2 consumption'Ķ), which is, of course, a major patient-safety issue. The use of such ventilators would therefore be strongly conditioned by the possibility to monitor ventilation parameters. Archeon has recently developed a medical device that provides caregivers with ventilation monitoring and real-time feedback on the quality of ventilation given to cardiac arrest patients. The system has been tested successfully in different mass casualty incident simulation scenario and has proven a drastic improvement of ventilation quality (75%). The aim is now to develop and implement the first independent monitoring system dedicated to mechanical ventilation at a very low-cost so that it could massively equip every hospital and care centre in the event of mass casualty incident or viral pandemic. This technology could save a very large number of lives as was demonstrated that avoiding hyperventilation decreases mortality from 34.1% to 19.6% in the intensive care unit. With the necessary resources, the project can be completed very quickly as Archeon already has all the know-how and technology available.",,2023,ARCHEON,1200000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing | Innovation,,,France,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23503,101082079,Quartz On-chip for Virus Detection,"The global-scale pandemic crisis of COVID-19 requires precise and immediate technological solutions for virological and serological diagnosis tests. These tests must be accurate, rapid, intelligent, and cost-efficient to prevent future rebounds of infections and help control the pandemic. In this context, the Microelectromechanical Systems (MEMS) industry, especially piezoelectric resonators of all shapes and sizes, is a promising strategy to revolutionize the biological detection market. Ultrahigh sensitive nanomechanical resonators showed the potential of this technology for mass loading. Unfortunately, applying MEMS to the biomedical sector requires challenging qualities, making it often unattainable to material scientists and engineers. QOVID offers a solution to fill this gap between MEMS and biomedicine by developing a commercialization solution for piezoelectric Œ±-quartz resonating devices to detect the mass response of SARS-CoV-2 spike molecular interactions as an original readout of viral loads. QOVID builds on the technology developed during the ERC Starting Grant SENSiSOFT to provide a user-friendly versatile Bio-MEMS sensor prototype that will give researchers in the life sciences and biomedical sector without an engineering or electronic training a reliable diagnostic tool to detect SARS-CoV-2 and other respiratory viruses. QOVID will scale up a new generation of On-chip epitaxial piezoelectric Œ±-quartz/Si MEMS manufactured exclusively by soft-chemistry with CMOS-compatible processes offering cost-efficient single-chip solutions not only for biomedical applications but also for many other fields. These Œ±-quartz bioMEMS will have thicknesses between 200 nm and 1 ¬µm, this is between 10 to 50 times thinner and 10 to 100 times more sensitive than those obtained by traditional top-down technologies on bulk crystals. QOVID will pursue commercialization and market solutions both within academia and the biotechnology and biomedical among other sectors.",,2024,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,145500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23504,101046787,ECL-based Infectious Pathogen (bio)SEnsor,"Infectious diseases are a threat to mankind since their appearance in human history. Despite the advances in science and technologies, such threats are still recurrent, as recently shown by the COVID-19 pandemic in 2020 'Äì 2021, which has revealed the urgent need for novel tools for pathogen detection that would be at the same time reliable, fast, cheap, portable and simple. The goal of ECLIPSE is to address this need, with a new platform exploiting innovative ultrasensitive protocols for the detection of pathogens. ECLIPSE builds on the combination of interdisciplinary elements to facilitate the transfer to industry, i.e., (i) ElectroChemiLuminescence (ECL) as a very sensitive transduction mechanism for realizing simple, portable and cheap devices, (ii) bio-, nano-, and supramolecular-based signal amplification structures for increasing the sensitivity, and (iii) two recognition strategies to afford high affinity and selectivity, thus leading to high reliability: the Phage-Sandwich technology for the whole pathogen, and the Surface Cooperative Hybridization technology for microbial and viral nucleic acid. We will demonstrate the feasibility and adaptability of the ECLIPSE platform with three test cases: a virus (SARS-CoV-2), a bacterium (Pseudomonas aeruginosa) and a protozoan parasite (Leishmania infantum). The platform is designed to be applied to many other infectious agents, making it a ""ready for the next pandemic'Äù technology. ECLIPSE is expected to become a game-changer in European countries, where it could be a cornerstone for fast testing and reliable tracking of infections, and in developing countries that will benefit from a cheap and simple approach to detect the many infectious diseases that affect millions of people every year. The project results will be validated and demonstrated at partners'Äô premisses.",,2025,ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA,2818195.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Italy,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23505,101095606,Impact and viability of a novel mass PCR testing method as a pandemic-fighting strategy,"The COVID-19 pandemic has not only affected our health, but also our lifestyles and our economies. Given its high non-symptomatic transmissibility, to stop a pandemic-causing pathogen like SARS-CoV-2 early on its tracks without needing to resort to economy-damaging measures, would have required a mass testing strategy very early on: according to some estimates up to 10% of a nation'Äôs population should have been tested on a daily basis to achieve this. Given the exponential growth tendency of pandemic-causing respiratory viruses, as soon as such pathogen is identified a large-scale testing campaign should immediate be deployed (a strategy adopted successfully in very densely populated areas of China). And given the long periods required to develop other pandemic-fighting strategies (i.e. such as vaccines and quick diagnostic tests), PCR-based mass testing could be the ideal front line of defense, since it can be developed in only a few weeks after decoding the genetic map of the pathogen. But although PCR testing capacity has greatly been increased worldwide, regularly testing large fractions of the population would still remain prohibitively costly with current technology. The PCR-4-ALL consortium (combining expertise in diagnostics, high-throughput-screening, virology, disease modelling, econometrics and digital health platforms) will aim to demonstrate the technical feasibility of carrying out population-wide PCR testing by demonstrating a capacity of >10^5 tests in a single day and platform, in an extremely cost-effective manner (at least 2 orders of magnitude cheaper than currently). We will, furthermore, evaluate the effectiveness of utilizing this strategy as the main pandemic-fighting measure by assessing its ability to minimize, or even prevent, the need to implement other costly and partially ineffective measures (i.e. lockdowns and vaccination campaigns).",,2026,KATHOLIEKE UNIVERSITEIT LEUVEN,3567491.55,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Belgium,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2022 +P23506,101112962,"Streamlining laboratory procedures, bioinformatics and integrating use of genomic data in infectious disease surveillance in Finland","In the HERA funded project 'ÄúEnhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the Covid-19 pandemic in Finland'Äù national technical resources for genomic surveillance of SARS-CoV-2 and other infectious diseases were improved. The aim of the current project is to take improved technical resources into routine use. The project is divided in three work packages (WP) progressing in parallel. In WP1 Laboratory methodology and procedures we aim to develop and harmonize methodology for genetic surveillance of microbial infections including viruses and bacteria. In WP2 Public health microbiology bioinformatics in Finland we will streamline processes for genetic data analyses including data collection, transfer, storage, bioinformatical analysing and dissemination of results. In WP3 Surveillance systems we will integrate the produced and collected genetic data to surveillance systems and enhanced utilization in outbreak investigations, communication, and modelling. The Finnish Institute for Health and Welfare (THL) will be responsible for the project lead with clinical microbiology laboratories in Finland acting as associated partners. The duration of the project is 24 months.",,2027,TERVEYDEN JA HYVINVOINNIN LAITOS,1968911.69,Bacteria | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Finland,,Epidemiological studies,Disease surveillance & mapping,2023 +P23507,101092049,MULTIFUNCTIONAL MICROFLUIDIC PATCH FOR INFECTIOUS DISEASES DIAGNOSIS,"In vitro diagnostic (IVD) technologies have revolutionized healthcare, yet remain confined to the laboratories. As witnessed during the COVID-19 pandemic, this traditional centralized approach was not sufficient to prevent and manage viral outbreak because it massively failed to deliver quick and cost-effective diagnosis. The ongoing pandemic further emphasizes the growing need to urgently bring lab-quality diagnosis to the hands of end users (i.e. point-of-care, POC). Despite high expectations from Lab-on-Chip technologies, they failed so far to disrupt the IVD market due to their complexity of integration/operation, high cost, off-chip sample preparation, poor scalability, to mention only a few. The FORTIFIEDx consortium aims to revolutionize the POC IVD field by making use of novel multifunctional biocompatible polymers and their (micro)structuring with mass fabrication technology to develop for the first time a true sample-to-result POC test. We will develop a FORTIFIEDx microfluidic-based patch capable of both biofluids (self-)sampling via hollow microneedles and immediate analysis of this sample on the very same patch in a completely self-powered manner. Two unmet clinical needs, posing epidemic/pandemic treats to both the developed and developing world, are selected: (1) sexually transmitted diseases, in particular simultaneous diagnosis of HIV and Syphilis, to enable timely diagnosis of patients not always able to reach centralized settings due to stigma or financial difficulties and (2) viral haemorrhagic fever, in particular Ebola and Lassa viruses, to battle their highly contagious and deadly outbreaks. To tackle this challenging aim, the interdisciplinary and experienced FORTIFIEDx consortium (2 universities, 5 research institutes and 2 SMEs from 6 countries) will combine insights from material science, engineering and microfabrication, microfluidic technology development, bioassay development, clinical validation and life cycle assessment.",,2027,KATHOLIEKE UNIVERSITEIT LEUVEN,5484677,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Arenaviridae | Filoviridae,,,,,,,,,Lassa fever | Ebola virus disease,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Belgium,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P23510,101095712,"One Health approach to understand, predict and prevent viral emergencies from bats","In recent years, several novel RNA viruses found in bats have been associated to the emergence of human diseases. Surveillance in this extremely diverse group of mammals has revealed that bats are significant reservoir hosts for many viruses whose zoonotic potential deserves further insights. OneBAT aims at investigating the trigger for viral spillover from European bats to humans or domestic animals, using a multidisciplinary consortium of ecologists, virologists and modellers. In response to the outcomes foreseen by the call, OneBAT will unravel the complex interplay between natural and spillover host, pathogen and environment that determines the emergence of infectious diseases. Information on viral replication pathways, antigenic markers, and in vitro and in vivo screening of antivirals will advance the availability of current and future therapeutic and prophylactic tools for Disease X. Due to technical and logistical reasons, OneBAT will not investigate all the bat species and pathogens circulating in Europe; it will rather provide well-based evidence on relevant model species that could be used to study other bat species or viruses that already are or may become of interest over the lifetime of the project or in the future. We will focus on the Miniopterus schreibersii bats, a species in significant decline across Europe, and on filoviruses, coronaviruses and lyssaviruses, as high-consequence pathogens known to circulate in the target bat. In addition to the specific information stemming from the project, OneBAT will establish a methodological platform that will make available the developed ecological and virological tools. Among them, innovative protocols for serological and virological investigations of these small-seize animals; harmonised longitudinal surveys across Europe, including tracking systems. Ultimately, OneBAT will equip southern and eastern EU countries with 20 VHF receivers that could be used for further studies on all flying animals.",,2026,ISTITUTO ZOOPROFILATTICO SPERIMENTALE DELLE VENEZIE,2313293.92,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology,2023 +P23511,960137,Automate ISO-certified DNA screening platform to enhance the global food supply chain,"Food recalls, costly mitigation measure following the evidence of contaminated, adulterating or counterfeiting foods are daily. It can cost several milions to take back the food company and cause severe damages to the brand. Lab tests, detecting food contaminants can take up to seven days and are thus not compatible with fresh-food processes. The BEAMit-up platform that will bring the global food supply chain to the upper level of safety is composed of a hardware, capsules and a cloud solution. The capsule integrates a rapid DNA screening, developed and patented by SwissDeCode. Placed at the point-of-care, the BEAMit-up platform will certify the presence of pathogens or identify pork in beef meat in only 30 minutes. An ISO 17025 certificate will be released by SwissDeCode for each test. We will validate the BEAMit-up platform early access programs: We supply hardware and capsules to the customer who will perform a pre-defined number of tests per week. We will investigate the presence of Listeria, milk proteins, and pork. We will also use the platform to certify cheese and basmati rice. SwissDeCode estimates a positive EBITDA at 5 years of 'Ǩ6.8M with a company growth to 200 employees. To tackle the SARS-CoV-2, rapid and accurate detection methods are needed. Since the beginning of March, SwissDeCode collaborates with The Genova Hospital to extend the core technology to the detection of the virus. Preliminary tests were sent to the virology labs of the hospital and will be tested with patient samples. With the support of the EC, SwissDeCode can bring this new test to the hospital within few months only.",,2022,SWISSDECODE SA,2949646,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23512,101069369,Methyltransferase inhibitors for treatment of COVID19,"Our IP secured drug DZNep is effective in treating SARS-CoV-2 infections in preclinical disease models and uniquely suppresses virus growth, triggers the innate immunity and facilitates tissue regeneration. The ERC-PoC will enable the transition from preclinical to clinical research.",,2023,TECHNISCHE UNIVERSITAET MUENCHEN,160500,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P23513,101113109,Consolidation of WGS and RT-PCR activities for SARS-CoV-2 in Spain towards sustainable use and integration of enhanced infrastructure and processes in the RELECOV network,"We aim to consolidate a national laboratory network (RELECOV) for a sustainable and collaborate platform to obtain virological information about SARS-CoV-2 variants/lineages for the integration of the genomic sequencing in the surveillance of SARS-CoV-2. We will enable timely data sharing through a coordinated response, allowing for investigation of variants/lineages with low or wide geographical reach. This will be achieved through integration, adaptation and consolidation of the existing Spanish RELECOV network designed by public health agencies at regional and national level. Conducting a genomic based surveillance of SARS-CoV-2 we will extend to other viral respiratory infections through the update of the current network to make it more practical and technically more efficient after a validation and an specific verification of processes. Now RELECOV 2.0 will address the identification of circulating VOCs, lineages and sublineages of SARS-CoV-2 and even of the new emerging lineages/sublineages. We will focus our efforts in constructing a national platform for genomic surveillance applied to respiratory viral infection, rapidly adaptable to other future emerging pathogens and contributing to international pandemic preparedness. Through protocol sharing and pooling of results at national level, questions will be answered more efficiently than by the Autonomous Regions acting alone. It is mandatory that RELECOV 2.0 is integrated and at the service of the different public health agencies involved in surveillance at regional and national level, and collaborate with other genomic networks and initiatives existing in Spain to create synergies for rapidly contributing to public health preparedness and response to future health threats.",,2025,INSTITUTO DE SALUD CARLOS III,1918767.33,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Spain,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2023 +P23514,101018317,Population Health Information Research Infrastructure,"A structured European mechanism for COVID-19 exchange to organize and share information between countries is urgently needed, especially in the area of population health. Information on the broader impacts of COVID-19 on the health of populations is needed to facilitate multidisciplinary European research and underpin decision making. PHIRI aims to facilitate and support open, interconnected, and data-driven research through the sharing of cross-country COVID-19 population health information and exchange of best practices related to data collection, curation, processing, use and reuse following ELSI and FAIR principles. It has the objective: to provide a Health Information portal for COVID-19 with FAIR catalogues on health and health care data, to provide structured exchange between countries on COVID-19 best practices and expertise, and to promote interoperability and tackle health information inequalities. To this end, it builds with national nodes a Health Information portal (WP4) on data sources, population health studies, training material and courses, considering ethical and legal aspects. The portal is supported by WP7 that provides the technological substrate for the development of a federated research infrastructure. WP5 develops a consolidated framework to assess the direct and indirect impacts of COVID-19 on population wellbeing, morbidity and mortality. WP6 will look at COVID-19 impacts in specific subgroups by conducting research through use cases of immediate relevance and facilitates research by making scalable, reproducible methods available within PHIRI. WP8, the Rapid Exchange Forum, provides swift responses to research and policy questions that are raised in countries to handle the COVID-19 pandemic. WP9 gains insights in possible future health impacts of the coronavirus outbreak by modelling scenarios for national situations. This will be carried out in close collaboration with different types of actors and initiatives across Europe (WP3).",,2023,SCIENSANO,5826983.76,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Belgium,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health information systems,2020 +P23515,101030824,Growing Up in a Pandemic: health behaviours and the impact of COVID-19 on health inequalities among young people in Ireland,"The coronavirus (COVID-19) pandemic has brought health inequalities into sharp focus and exposed the structural disadvantage experienced by people facing the greatest deprivation. Research studies such as Growing Up in Ireland (GUI) and TeenPath at Trinity College Dublin (TCD) and the Royal College of Surgeons Ireland (RCSI) are specifically documenting these inequalities in the lives of children and young people in Ireland pre-COVID-19. This proposal will integrate with the TeenPath study and its aims to centre young people in the development of public health policy targeting adolescent health, with a view to addressing longer term health inequalities revealed and potentially exacerbated by the pandemic. Despite their behaviours being subject to high levels of public scrutiny and social policing throughout the pandemic, young people have limited power to influence society'Äôs response to it. Rapid studies have generated snapshots of the experiences of people living through the COVID-19 outbreak in Ireland, but largely overlook how young people'Äôs routines and emotional wellbeing have adapted. This project will take participatory and social network approaches to investigate how adolescents in Ireland have experienced COVID-19, and will address intersectional dimensions including gender and ethnicity to examine disproportionate impacts of the pandemic on health inequalities. Working with the TeenPath project at RCSI in partnership with TCD, this interdisciplinary project will bring together Public Health, Anthropology and Sociology to deploy innovative approaches such as Photovoice and Social Network Analysis to centre young people in the co-development of public health policy. This co-designed, inter-sectoral and participatory project will contribute to understanding of the impacts of COVID-19 on young people and health inequalities in Europe through policy-focused research, while developing my interdisciplinary skills as an independent public health researcher.",,2023,ROYAL COLLEGE OF SURGEONS IN IRELAND,219663.29,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P23516,101111879,Strengthened capacity and Sustainable Infrastructures for Sequencing-based diagnostic preparedness,"Statens Serum Institut (SSI) is the national public health institute under the Ministry of Health and works to prevent and fight infectious diseases and congenital diseases through research, monitoring, diagnostics, and advice. During the SARS-CoV-2 pandemic SSI was the primary coordinator of the national SARS-CoV-2 response and WGS capacities both at SSI and at the Departments of Clinical Microbiology (DCM) in the five regions of Denmark was increased substantially. However, the SARS-CoV-2 workflow and infrastructure was developed during the fluctuating epidemic and is not directly applicable to other pathogens of interest. SSI will therefore, based on thorough dialogue with external national and international stakeholders, work to fulfill the three primary needs identified. One need is to optimise and further develop surveillance-related pipelines and workflows to secure that WGS data for surveillance is of comparable quality. A second need is to develop IT infrastructures and bioinformatics tools that allows for sharing WGS data and analysis results in as real-time as possible. A third need is to develop common Standard Operation Procedures (SOPs) for producing, analyzing and sharing of WGS data. In order for the generated WGS surveillance data to become data-for-action it is important that the combination of other laboratory data, epidemiological data, and WGS data are built into the supporting IT infrastructure. This will be addressed in all relevant work packages. SSI is committed to making data open and transparent where possible as we have carried out with our extensive sharing of data for SARS-CoV-2 to GISAID and ENA. This process is conducted for some of our other pathogen species but not all. We want to ensure we continue to disseminate information to National, EU and global institutes in a timely and understandable manner. Throughout the project, sustainability will be on the agenda.",,2026,STATENS SERUM INSTITUT,3959000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Denmark,,Epidemiological studies | Health Systems Research,Disease surveillance & mapping | Health information systems,2023 +P23517,101112671,Consolidation and Integration of Whole Genome Sequencing (WGS) into Routine Surveillance in Slovenia,"Within this grant proposal, three independent entities, already partners in HERA 2021, will continue to collaborate: NLZOH (national public health laboratory), UL-IMI (diagnostic and academic laboratory), and NIJZ (national public health institute). In line with the expectations of the Call and the EU4Health Programme¬¥s general objective to protect the people of the EU from serious cross-border threats (EU Regulation 2021/522), and national needs, we will continue to expand the project started under HERA 2021. We intend to develop further research on the established RT-PCR and WGS infrastructure. The objectives requested in the Call will be implemented in the technical/scientific part of the project; in WP 2 we will continue real-time national surveillance of SARS-CoV-2 and detection of known and emerging new SARS-CoV-2 variants. WP 3 will contribute to enhanced genomic surveillance of additional pathogens and integration of WGS for selected pathogens into routine public health activities. We will consolidate data analysis and enable high-quality results by development of pathogen-specific workflows and combining them in user-friendly open-source software (WP 4). In WP5 we will upgrade the existing genomic surveillance data pipelines and tools used for collecting SARS-CoV-2 surveillance data. In line with the general objectives of this call, we will ensure: better preparedness and response for public health threats, sustainability of public health microbiology system, shortcut to eHealth goals, rapid reporting of microbiological agents to patient's record and in e-based heath-system, progress towards common European Health Data Space, progress in implementing the European One Health Action Plan against Antimicrobial Resistance, maintain and strengthen genomic surveillance and epidemic response capacities in Slovenia and data sharing across various public domains.",,2025,"NACIONALNI LABORATORIJ ZA ZDRAVJE, OKOLJE IN HRANO",1172840,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Slovenia,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2023 +P23518,101057548,Epigenetic regulation of host factors in viral infections (EPIVINF),"The EPIVINF project aims to gain a deep understanding of how acute viral infections alter the epigenetic regulation of host factors that are critical for immune control and neurological health. In particular, EPIVINF will address how acute viral infections impact epigenetic control of host proteins that drive virus-associated disease and/or are involved in the antiviral immune response and how such persistent, epigenetic marks are related to long-term disease evolution. EPIVINF will focus on two major human viral infections, HIV and SARS-CoV-2, both pathogens that affect millions of people around the world and which, despite well-known differences, share some intriguing features that demand further research. We hypothesize that a) defining individuals personal epigenetic profiles, b) assessing how they impact on the innate and adaptive immunity and c) analysing epigenetic control mechanisms in two different viral infections (HIV and SARS-CoV-2), will provide important insights into how different individuals react to different viral infections, how different infections may share similar mechanism that impact on the long term health outcomes, how these processes define the further disease course and, finally, how they could serve as targets for novel therapeutic interventions. To achieve these goals, we will use an panel of cutting-edge epigenetic analyses, immune monitoring tools, disease-relevant animal models, samples from unique human vaccine trials and integrated biosystems analyses to gain a deep understanding of how viral infections harness epigenetic mechanisms to change the adaptive and innate immune phenotype of infected individuals, not only during acute stages of the infection but potentially for live. The study includes extensive patient follow-up to identify factors that predispose to different clinical symptoms and disease progression.",,2027,FUNDACIO PRIVADA INSTITUT DE RECERCA DE LA SIDA-CAIXA,6932308,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity",2022 +P23519,101003589,Rapid European SARS-CoV-2 Emergency research Response,"RECoVER (Rapid European SARS-CoV-2 Emergency Research response) is a comprehensive research response to the SARS-CoV-2 outbreak addressing the most urgent questions for patient and public health level interventions. RECoVER originates from partners of the EU Framework 7 (FP7) funded PREPARE project (Platform for European Preparedness Against (Re-) emerging Epidemics. In RECoVER, we will address these urgent questions in a comprehensive, multidisciplinary and interacting set of research response activities, combing (i) clinical studies in primary and hospital care, (ii) epidemiological studies and modelling, and (iii) clinical biological studies. The proposed studies complement ongoing research in China, addressing key knowledge gaps and patient-cohort questions relevant to the European population. The research proposed includes essential needs for preparedness and response, even if circulation of the virus in Europe will be limited. RECoVER will inform future research response efforts to further strengthen Europe'Äôs and global clinical research preparedness to future emerging infectious diseases.",,2023,UNIVERSITEIT ANTWERPEN,21594810.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Belgium,,Epidemiological studies | Clinical characterisation and management,,2020 +P23520,101081290,Clinical development of Rift Valley fever vaccines in endemic regions,"Initial funding was provided to the Coalition for Epidemic Preparedness Innovations (CEPI) in 2019 which was used to support preclinical and clinical development of Rift Valley fever (RVF) and Chikungunya (Chik) vaccines respectively. This funding was provided to applicants as a joint effort between CEPI and the Horizon 2020 programme, under the CEPI Call for Proposals CfP3i. Whilst previous funding has led to the development of pre-licensure Chik vaccines, development of RVF vaccines is at a much earlier stage. Hence, this current application seeks to leverage a further 'Ǩ35M from Horizon Europe, which will be supplemented with 'Ǩ15M from CEPI, making a pool of 'Ǩ50M, which will be used to fund clinical development of RVF vaccine projects under the CEPI follow-up Call for Proposals CfP3ii. It is envisaged that applicants for the CfP3ii funding will have already developed a manufacturing plan and that all preclinical studies have been completed (with the possible exception of Development and Reproductive Toxicology (DART) studies). Applicants will propose Phase I/II trials in endemic regions for vaccines which are in accordance with the WHO Target Product Profile (https://www.who.int/docs/default-source/blue-print/call-for-comments/tpp-rift-valley-fever-vaccines-draft3-0pc.pdf?sfvrsn=f2f3b314_2) for RVF vaccines. Awards will usually have a 36-month duration and will be administered by the CEPI secretariat.",,2026,COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS,35700000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Bunyaviridae,,,,,,,,,Rift Valley Fever,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Norway,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2022 +P23521,101084171,Ecology and biology of HPAIV H5 (Kappa-Flu),"The global emergence of highly pathogenic avian influenza (HPAI) viruses and the subsequent adaptation to wild birds has resulted in record mortality of wild birds and poultry and is developing into an enzootic threat for wildlife, poultry and human health in Europe. The ongoing evolution of HPAI viruses is expanding their geographical distribution and host range. To deal with this global problem, KAPPA-FLU brings together top experts from Europe, North America and Asia. The overall objective of KAPPA-FLU is the characterization of key viral, host-related and environmental factors that determine the maintenance and the long-distance spread of HPAI viruses in wild birds, with the goal of improving capacities for risk-based surveillance, prevention and control of HPAI in poultry and wildlife, and its potential impact on human health. KAPPA-FLU will follow three research themes. Theme A (Disease ecology) provides a deep understanding of the population dynamics of HPAI viruses in migratory waterbirds and spill-over hosts, both resident wildlife and poultry, through risk-based surveillance strategies, and accounting for the impact of climate change. Theme B (Virology) studies the evolution of HPAI viruses in wild birds and poultry and the resulting increasing risk to humans and other mammals. Based on the above results, theme C (Agro-ecosystem risk) identifies and models prevention and control strategies (including vaccination) using machine learning algorithms. Actors from different sectors of society will, through the Multi-Actor Panel, play key roles in translating results into policy and practice. In this way, KAPPA-FLU will make stepwise advances in knowledge of the population dynamics and evolution of HPAI, and thus contribute to a sustainable poultry production system and improved public health.",,2027,FRIEDRICH LOEFFLER INSTITUT - BUNDESFORSCHUNGSINSTITUT FUER TIERGESUNDHEIT,4636500,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,,,,,Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Vector control strategies,2023 +P23522,101017915,Edge AI-deployed DIGItal Twins for PREDICTing disease progression and need for early intervention in infectious and cardiovascular diseases beyond COVID-19,"The interplay between viral infection, host response, development of (hyper)inflammation and cardiovascular injury in COVID-19 is currently poorly understood which makes it difficult to predict which patients remain with mild symptoms only and which patients rapidly develop multi organ failure. The solution offered by DIGIPREDICT is an Edge Artificial Intelligence (AI) based, high-tech personalized computational and physical Digital Twin vehicle representing patient-specific (patho)physiology, with embedded disease progression prediction capability, focusing on COVID-19 and beyond. DIGIPREDICT proposes the first of its kind Digital Twin, designed, developed and calibrated on i) patient measurements of various Digital Biomarkers and their interaction, ii) Organ-On-Chips (OoCs) as physical counterpart using patient blood for personalized screening and iii) integration of those physiological readouts using AI at Edge technologies. The final goal is to identify and validate patient-specific dynamic digital fingerprints of complex disease state and prediction of the progression as a basis for assistive tools for medical doctors and patients. Using and improving state-of-the-art OoCs and Digital Biomarkers (for physiology and biomarkers in interstitial fluid) we will measure detailed response to viral infection. By closely monitoring the response with wearable multi-modal Edge AI patches, we aim to predict in near real-time the progression of the disease, support early clinical decision and to propose patient-specific therapy using existing drugs. We will combine scientific and technical excellence in a highly multi- and inter-disciplinary project, bringing together medical, biological, electronical, computer, signal processing and social science communities around Europe to setup Digital Twin at Edge. We will enable an Edge-to-Cloud vision, significantly advancing current state of the art and setting up a new European community for researching and applying Digital Twins.",,2024,ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE,7353363.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +P23523,101005111,A minituarized disposable molecular diagnostics platform for combatting coronavirus infections,"The DECISION consortium is developing a new class of diagnostic platform that will transform the fight against pandemics. The low-cost, miniaturised, disposable molecular diagnostic platform will allow for patient testing virtually anywhere, within a few minutes, with laboratory quality performance. The diagnostic platform will enable rapid detection of Covid-19 infections on-site in a multitude of settings including drive-through testing centres, physician offices, airports, hospitals and quarantine centres. First demonstrators of the disposable molecular diagnostic platform and coronavirus test will be available five months after the start of the project and could be provided to emergency first responders and public health authorities. The platform is powered by a next-generation nucleic acid amplification technology called Pulse Controlled Amplification (PCA¬Æ), which enables sample-to-answer workflows in 15 minutes or less. The DECISION consortium is comprised of teams from Italy, Spain and Germany, and is highly motivated to develop a ground-breaking diagnostic solution to help the serious crisis faced across the world due to the Covid-19 epidemic.",,2024,AIT AUSTRIAN INSTITUTE OF TECHNOLOGY GMBH,3847312,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Austria,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23524,101107066,"Human dimensions of biodiversity conservation: Wildlife trade, COVID-19 and geopolitics","The catastrophic global decline of biodiversity is one of the most pressing problems facing humanity. Effective conservation solutions must be informed by evidence. Conservation policy and practice historically relied solely on the natural sciences for guidance, but there is increasing recognition that considering the human dimensions of conservation is vital. These are complex and span diverse fields of classic and applied social sciences, and are particularly pertinent for problems which are inherently the result of human decisions and actions, such as wildlife trade. Wildlife trade is a major driver of biodiversity loss and a pathway for zoonotic disease transmission. Illegal and unsustainable wildlife trade is a significant threat, placing ~12,000 terrestrial vertebrate species (ca. one quarter of the total) at risk of extinction. Furthermore, the rising frequency of zoonotic epidemics and pandemics, including COVID-19, has highlighted the devastating human health consequences of wildlife consumption. Shifting global power structures and geopolitics add to the complexity of the challenges faced. Improved wildlife trade governance and environmental governance in biodiversity-rich areas is needed to manage zoonotic disease risks and implement integrated preventative approaches like One Health. How can wildlife trade governance address the challenges of our geopolitically polarized, post-pandemic world? In the HUMAN-CONSERVATION project, I will pursue three Research Objectives on the human dimensions of wildlife trade. Building on my expertise on the human dimensions of wildlife trade, my ability to lead interdisciplinary collaborations, and Prof. Di Marco'Äôs strengths in comparative species modelling and in using integrated approaches to connect conservation solutions to broader societal goals like human health, the HUMAN-CONSERVATION project will inform wildlife trade policy, help combat wildlife trafficking, and define frontiers in conservation geopolitics.",,2025,UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA,188297.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P23525,190136873,Accelerating scale up and commercialisation of 100% bacteria free eggs for use in production of vaccines,"Ovagen is aiming to transform the egg-based production of vaccines and other biopharmaceutical medicines by producing the world'Äôs first Germ Free egg and bringing it into mass production. The proposed programme of work will build on the groundwork initiated as part of the 30 month OvaVax project (GA 858390) and provides a logical expansion of this disruptive, innovative technology to the challenges facing the world as it comes to grips with COVID-19 and future pandemics with the need for rapid scale-up of vaccine production Ovagen is applying for EIC Accelerator funding to broaden the project scope of their existing H2020 SME Instrument Phase 2 to expand and accelerate the existing influenza project, to include COVID-19, Yellow Fever, Newcastle Disease and to include readiness for production and accelerated international scaleup of germ free egg production to increase global vaccine manufacturing capacity in readiness for future pandemics similar to COVID-19.",,2024,OVAGEN GROUP LIMITED,2475000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Other,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Ireland,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P23526,101043543,Politicians under Radical Uncertainty: How Uncertain Phenomena Influence Political Elites' Behavior,"Political elites-political representatives who can take binding decisions, e.g. ministers, parliamentarians, local politicians-face numerous radically uncertain phenomena, from Covid-19 to the long-term effects of Brexit. Radical uncertainty is characterized by manifold unknowns, ambiguity and vagueness, and it differs fundamentally from resolvable uncertainty, those situations in which it is possible to assign probabilities to outcomes, like the electoral consequences of welfare retrenchment. RADIUNCE will explore how these phenomena influence political elites' behavior. Do they ""avoid"" uncertainty, as some did with the coronavirus; use rules of thumb, ""heuristics"", e.g. comparing Covid-19 to the flu; or display other behavioral responses? Answering this is urgent: different responses have different outcomes that may impact how representative democracies function and how effective they are at solving problems. For example, avoiding a virus may cost lives, while using heuristics may result in faulty courses of action. RADIUNCE's aim is to develop a theoretical model of how political elites respond to both radically and resolvably uncertain phenomena. We will focus on four countries with different institutional opportunities and constraints for responding to uncertainty: Germany, the Netherlands, the United Kingdom and the United States, 1996-2021. The model will be multidisciplinary, integrating insights from political science, behavioral economics, decision theory, psychology and public administration. We will collect new, unique comparative data from politicians through an innovative combination of automated text analysis and survey experiments. Taking a multimethods approach, we will integrate quantitative data with qualitative methods (process tracing, Qualitative Comparative Analysis, interviews). The new model will explain how political elites respond to the challenges and opportunities in our face-pace world from digitalization to Covid-19 to migration.",,2028,UNIVERSITEIT UTRECHT,2175012.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2023 +P23527,101016247,COronavirus Vulnerabilities and INFOrmation dynamics Research and Modelling,"Policymakers and public health experts unanimously recognise the disproportionate impacts of COVID-19 on vulnerable persons: even in countries with well-developed responses, the outbreak and its repercussions imperil the basic well-being of social groups whose livelihoods are already precarious, while the uneven distribution of suffering threatens to aggravate inequality and division. One complicating factor here is the intersectional nature of health and socioeconomic vulnerabilities. Another is the complexity of risk in contemporary socioecological systems. The COVINFORM project will draw upon intersectionality theory and complex systems analysis in an interdisciplinary critique of COVID-19 responses on the levels of government, public health, community, and information and communications. The project will conduct research on three levels: 1) on an EU27 MS plus UK level, quantitative secondary data will be analysed and models will be developed; 2) Within 15 target countries, documentary sources on the national level and in at least one local community per country will be analysed; 3) in 10 target communities, primary empirical research will be conducted, utilising both classical and innovative quantitative and qualitative methods (e.g. visual ethnography, participatory ethnography, and automated analysis of short video testimonials). Promising practices will be evaluated in target communities through case studies spanning diverse disciplines (social epidemiology, the economics of unpaid labour, the sociology of migration, etc.) and vulnerable populations (COVID-19 patients, precarious families, migrating health care workers, etc.). The project will culminate in the development of an online portal and visual toolkit for stakeholders in government, public health, and civil society integrating data streams, indices and indicators, maps, models, primary research and case study findings, empirically grounded policy guidance, and creative assessment tools.",,2023,SYNYO GmbH,5781737.52,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +P23528,101016262,Injection Moulding Repurposing for Medical Supplies enabled by Additive Manufacturing,"The modern world is fast-evolving, interconnected and highly mobile, thus posing a significant challenge in harmonizing risk mitigation measures against emerging biological hazards. For many years the risk of emerging infectious diseases with pandemic potential was declared a major threat to global health security and addressed by many stakeholders around the world. The delay in imposing risk mitigation measures is crucial and can make the difference between a local outbreak with few cases to a pandemic with countless sick and deceased citizens, as severely demonstrated by the recent outbreak of Coronavirus disease 2019 (COVID-19). It is of paramount importance that appropriate and proportionate measures to each phase of the pandemic (e.g. from situations with no reported cases, sporadic, local clusters of cases, to widespread sustained transmission) are immediately implemented to interrupt human-to-human transmission chains, prevent further spread and reduce the intensity of COVID-19 outbreak. Immediate activation of national emergency response mechanisms and pandemic preparedness plans to ensure containment and mitigation of COVID-19 with non-pharmaceutical public health measures is critical for delaying transmission or decreasing the peak of the outbreak, in order to allow healthcare systems to prepare and cope with an increased influx of patients. However, shortages and other gaps in the global medical supply chain represent a mismatch of supply and demand when supply is low and/or demand is high for particular items. With healthcare workers and other first responders feeling the impact of supply chains disrupted by unprecedented challenges, many large and small businesses from outside the traditional healthcare procurement system are reconfiguring to mass produce critical medical consumables. In order to address supply shortages, particularly in medical supplies and protective equipment, some countries have employed less traditional instruments.",,2022,ETHNICON METSOVION POLYTECHNION,6940560,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Greece,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23530,964553,Redefining mass spectrometry 'Äì a breakthrough platform for real-time noninvasive breath analysis with single ion detection of intact viruses and bacteria and post-analysis molecular characterization,"The extraordinary ability of the coronavirus to spread in the environment has established the Covid-19 pandemic as the biggest challenge humanity faces in the XXI century. Covid-19 attacks humans regardless of age, claiming the life of over 8,000 people in a single day, with a devastating death toll exceeding 350,000 in just a few months. The virus is likely to survive for the foreseeable future and disperse further, requiring long-term planning and investment in developing means of detection, protection and cure. Protective measures based on monitoring the dispersion of the coronavirus in the environment and fast screening of individuals has become paramount for ensuring safety of our ageing population and restarting/supporting the worldwide economy. The objective of the ARIADNE project is to develop a multiple-stage analytical platform based on multi-dimensional mass spectrometry instrumentation. Performing direct and instant detection of intact virus particles in breath and in water, and going far beyond that task, this unique analytical platform will push the scientific boundaries in all aspects of analytical sciences centered on mass spectrometry, incorporating a series of potentially disruptive technologies integrated into a single system. ARIADNE integrates state-of-the-art technological advancements in breath sampling and post-ionization methods, new analytical tools for characterization of the protein content of viruses by top-down mass spectrometry, non-destructive ultra-high mass analysis of single particles followed by their soft landing and further processing based on advanced single proteomic workflows. A compact and simplified version of this versatile and powerful analytical platform is also envisaged for advancing the field of real-time breath analytics. Applications extending the analytical capabilities of the system to new viruses, intact bacteria as well as whole human cells will also become accessible.",,2025,FASMATECH EPISTIMONIKI KAI TECHNOLOGIKI ANONYMI ETAIREIA,4858040,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Greece,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P23531,101068543,"Europe, Covid Politics and the (Un)Expected Surge of Nationalistic Narratives","In the face of the outbreak of the novel coronavirus, the unity of the European Union, at least at the beginning of the crisis, started to crumble. By closing their borders and introducing a travel ban for the Schengen Area, European countries have retreated into national fortresses. These initial policies and the recent vaccine-related management of the pandemic shows the role nationalism plays in the context of public health responses to emergencies, including evacuations and quarantines, travel and socio-cultural constraints. While many scholars have started to document the impact of these measures on citizens, human rights, migrants, and so on, almost no attention has been paid 1) to examine and to compare configurations of different European national identities that were generated in the course of the management of the pandemic, and 2) to a sociohistorical perspective to investigate the possible links between those nationalistic and war-related discourse and the exclusionary and inefficient policies and practices that surge in Europe and beyond. Eurosick will innovatively conjoin the sociology of migration and nationalism with research on historical disasters to fill this gap. It will do so, benefitting from my expertise in the analysis of discourse-practice nexus, and through an examination of media coverage of the COVID-19 pandemic and the related policy documents in three European countries (Belgium, Italy, and Switzerland); and in three points in time: before the outbreak in Europe, at the time of the outbreak, and at the beginning of 2021 following the implementation of the COVID-19 vaccination programmes. The analysis will be carried out using critical discourse analysis, an interdisciplinary approach used to study oral and textual discourses, which views language as a social practice. These learned lessons will impact the capacity of Europe to tackle the future crises in a more collective and efficient way.",,2024,KATHOLIEKE UNIVERSITEIT LEUVEN,103550.4,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Policy research and interventions | Social impacts,2023 +P23532,101022431,GENEtic VAccine technology and the coronavirus CRISIS: exploring socio-technical change and responsible innovation (GENEVACRISIS),"The coronavirus pandemic has disrupted our ways of living across the globe. This research project will use social science and humanities approaches to analyse the enabling role of the coronavirus crisis in the development and (potential) deployment of emerging genetic vaccine technology, and associated transformations in social values and scientific research practices. Although traditional routes are being utilised to develop vaccine candidates, the pandemic has thrown open doors for the introduction of the state of the art genetic vaccines as an emergency response, e.g. Moderna Inc.'Äôs vaccine candidate 'ÄòmRNA-1273'Äô. The underlying mRNA technology presents a completely new yet unproven therapeutic modality, which scientists believe has the potential to disrupt the drug development domain. In practice, only a few gene therapy approaches have received drug approval, and these are mainly aimed at treating rare hereditary conditions. In contrast, genetic vaccines would potentially be administered to the general population, both healthy and affected. They would hence normalise the mRNA medicine platforms. However, the state of the art mRNA therapeutics in general and genetic vaccine technology in particular is yet to undergo serious scrutiny and analysis from a social science perspective, a gap and original research problem that this project aims to address. The project will examine narratives around the Covid-19 pandemic, and through interviews and focus group discussions with scientists, policymakers, and science communicators will explore its enabling role in the introduction of genetic vaccine technology. Furthermore, it will analyse the ways in which these developments might shift social values and research practices. The research outcomes will provide key insights to policymakers for the governance of DNA and mRNA therapeutics platforms, and enhance social science understanding of how narratives of crisis co-shape our response to emerging science and technology.",,2024,THE UNIVERSITY OF EDINBURGH,267671.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions | Social impacts | Other secondary impacts,2021 +P23534,101003544,Combating 2019-nCoV: Advanced Nanobiosensing platforms for POC global diagnostics and surveillance,"The recent outbreak in China caused by the emerging nCoV virus is challenging the level of global readiness from governments, public organizations and community to face and manage both its social and health consequences. Once the emergence is recognized and identified, it is crucial to initiate the necessary measures to prevent the spread. This involves therapeutics, vaccines, and devising efficient, fast, readily accessible diagnostics methods that specifically confirm the presence of the virus. Early detection can allow the rapid implementation of containment measures, which are the key to reduce the risk of amplification. The aim of CoNVat is to implement a Point-of-care label free biosensor for the direct, fast and specific identification of nCoV in decentralized settings to improve its early diagnosis and the clinical management of patients. The approach employs an already developed technology based on nanophotonic bimodal waveguide (BiMW) interferometers capable of providing real time, highly sensitive detections assays in short sample turnaround times. We propose two different strategies: (i) the development of a fast antigen-based diagnostic test for the specific detection of the intact virus in patient'Äôs samples such as respiratory specimens and non-respiratory fluids (serum, urine'Ķ) to be deployed to clinical settings for initial screening and (ii) development of a multiplexed molecular test, PCR-free, for the reliable identification of nCoV, being possible to differentiate the type and strain of coronavirus form other related or more common respiratory viruses. This latter strategy will provide a disruptive diagnostic tool not only from a clinical perspective to improve patient'Äôs outcome but also for surveillance, to study and understand possible transmission routes of this virus by analysing samples from animal reservoirs. Final prototype validation will demonstrate the potential of this approach for the management of future infectious outbreaks.",,2022,FUNDACIO INSTITUT CATALA DE NANOCIENCIA I NANOTECNOLOGIA,2903753.28,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23535,101113409,Towards the National Platform for Genomic Surveillance,"The PLEpiSeq project is a continuation of the previous project - HERA I, which aimed at creating the bioinformatic platform for genomic-based national epidemiological surveillance in Poland. The platform provides (I) the infrastructure for genomic data storage and computations, (II) tools to support integrations of SARS-CoV-2 genomic sequence data with relevant metadata, (III) algorithms for improving the sequencing representation (algorithms generating random samples), and (IV) pipeline for standardized analysis of raw SARS-CoV-2 sequencing data obtained from laboratories in Poland. With this proposal, we aim to address the molecular epidemiology of other pathogens (i.e. Influenza virus and Salmonella). This will enhance epidemiological surveillance for these diseases in Poland, improve our understanding of how they evolve and spread, allowing for implementation of adequate disease control measures. Successful completion of the project will result in improved links between genomic data and contextual metadata and standardization of laboratory protocols, increase in capacity for advanced bioinformatic analysis and visualization of their results, as well as in building workforce capacity and networking in genomic surveillance. Overall, it will enhance our capacity for outbreak investigation, routine surveillance and responding to future health crises.",,2025,NARODOWY INSTYTUT ZDROWIA PUBLICZNEGO PZH - PANSTWOWY INSTYTUT BADAWCZY,1928999.23,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing | Innovation,,,Poland,,Epidemiological studies,Disease surveillance & mapping,2022 +P23536,101113520,Optimizing and expanding pathogen WGS infrastructure and capacity for public health purposes within the Kingdom of the Netherlands.,"With this proposal NLWGSHERA2 in Work Packages (WP) 5-7, the Netherlands will consolidate and enhance the work started under the HERA Incubator, NLWGSHERA1. Through this grant we will reach WGS capacity and capability for infectious disease Public Health (PH) hazards throughout the entire Kingdom. This includes establishing WGS by our Overseas Countries and Territories (OCT), strengthening the SeqNeth-network and enhancing the overall skill-base, expanding from SARS-CoV-2 WGS to other relevant pathogens and AMR, and to develop and pilot the new laboratory surveillance platform and corresponding processes. The project core team will remain the same and hence ensures continuity. For the OCT, in WP5 the aim is to start sequencing at both labs and to continue training and trouble-shooting the professionals of both labs (two islands) and all PH professionals of the six OCT. Additionally, to enhance multidisciplinary collaboration and facilitate decision making and prioritization processes concerning other pathogens for PH WGS and solutions addressing existing data sharing needs. For SeqNeth, in WP6 we continue the development of the WGS training materials, continue offering training and facilitate and enhance intra- and interregional and national multidisciplinary collaboration and knowledge transfer. This includes prioritization and decision making processes for both other pathogens to sequence and data sharing platform and processes. For data sharing, in WP7 a pilot implementation of the laboratory surveillance platform will be made and further developed in close collaboration with all stakeholders involved at national and regional levels. By the end of the project we will have delivered among reports, a plan on sequence reporting also internationally and on continuation/sustainability and advancement of the work.",,2027,RIJKSINSTITUUT VOOR VOLKSGEZONDHEID EN MILIEU,1634998.91,Bacteria | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Epidemiological studies,Disease surveillance & mapping,2023 +P23537,101063551,Inverting Œ±-glucosidase inhibitors as potential drugs for SARS-CoV-2,"Viral infections are still a major challenge in medical therapy. The recent outbreak of SARS-CoV-2 has again shown the immense threat these pathogens pose. In contrast to the direct-acting antivirals approach (targeting viral proteases, polymerases or other viral enzymes involved in replication), which is mostly followed by the pharmaceutical industry, this proposal targeting host cell enzymes involved in the biogenesis of infectious virions. In this context inverting Œ±-glucosidases are of special interest. They play an important role in cell functions, such as the correct folding of proteins in the endoplasmic reticulum (ER). However, up to now selective inverting Œ±-glucosidase inhibitors are scarce, and chemical probes that report on these selectively in biological samples non-existent. The dedicated aim of this proposal is to overcome this absence of inhibitors and probes. To identify novel inhibitors, activity-based protein profiling (ABPP) will be applied. This powerful analytical method is a driving force in chemical biology and medicinal chemistry but depends heavily on the availability of mechanism-based enzyme inhibitors. Based on current knowledge on retaining Œ±-glucosidase inhibitors, unprecedented inhibitors and probes for inverting Œ±-glucosidases will be developed and applied to ABPP. Their synthesis follows a divergent synthesis method to efficiently produce a wide library of compounds, that will be screened on the target enzyme, human ER Œ±-glucosidase I. As the work on retaining Œ±-glycosidase has shown, inverting Œ±-glucosidase inhibitors are likely to be important tools for advancing many areas of application that are outside the primary scope of the proposed research (antiviral agents). Overall, my proposal on inverting Œ±-glycosidase inhibitors and probes will therefore make a significant contribution to the current state of the art in glycan research.",,2024,UNIVERSITEIT LEIDEN,203464,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P23538,101062524,Role and modulation of Zinc-finger antiviral protein and antiviral Regnase-1-like endonucleases,"The human zinc finger antiviral protein (ZAP) is capable of inhibiting several major human pathogens, including Influenza A virus and SARS-CoV-2. ZAP specifically targets CpG dinucleotides in RNAs and might be one of the reasons why CpGs are strongly suppressed in the human genome. Successful viruses, such as HIV-1 and SARS-CoV-2, mimic human CpG suppression to partially evade the inhibitory effects of ZAP. However, especially under conditions of infection or inflammation when ZAP is expressed at high levels, it inhibits both CpG containing viral as well as cellular RNAs. Importantly, ZAP itself does not possess RNAse activity and is dependent on cofactors, such as KHNYN, to destroy viral RNAs. KHNYN is tightly regulated and inactivated by MALT-1, a cellular protease representing an important target in cancer immunotherapies. Although some progress has been made, the identity of ZAP cofactors as well as their mechanism(s) of action and therapeutic potential are poorly understood. This proposal aims to combine the expertise of the applicant (mechanistic studies of ZAP and RNA-targeting factors) and the host (respiratory viruses and antiviral drug development) to define how ZAP-dependent and independent antiviral endonucleases restrict major respiratory viral pathogens. In addition, it will be examined whether MALT-1 inhibitors that are currently in clinical trials against cancers allow to enhance and maintain the antiviral activity of ZAP and its cofactors thus offering prospects for the treatment of respiratory infections. Finally, potential side-effects on cellular RNAs and their impact on immune signalling, cell activation and infection outcome will be determined. The project will combine innovative CRISPR/Cas9 genome editing, in vitro virus infection platforms, novel functional assays and state-of-the-art deep sequencing technologies to significantly advance the knowledge on antiviral RNAses and to clarify whether they can be strengthened for antiviral therapy.",,2024,UNIVERSITAET ULM,172108.53,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P23539,101112981,NPHSL proposal for HERA 2 (EU4H-2022-DGA-MS-IBA-01-02),"C/WGS project'Äôs aim is to enhance existing WGS technologies and their capacity to respond not only to new emerging SARS-Cov-2 variants, but also to other pathogens of concern in Lithuania. This project is the continuation of previous project Grant/2021/PHF/23776 and ensures the support and extension of previously implemented technologies. Significant objectives of this project would be: the use of existing technologies for implementation of new assays, improving previously implemented integration systems and initiation of new integration systems for other than SARS-CoV-2 pathogens; sustainable workflow optimization, further personnel training and increasing the visibility of the project to the public.",,2025,NACIONALINE VISUOMENES SVEIKATOS PRIEZIUROS LABORATORIJA,1089638.12,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Novel Pathogen | Unspecified,,,,,,,,,COVID-19 | Disease X | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing | Innovation,,,Lithuania,,,,2023 +P23541,101056852,European Group for Accreditation and Liaison of Blood-Tissues and Cells Establishments,"The organisations involved in the activities with Substances of Human Origin (SoHO), saw their activities severely impacted by the Coronavirus disease 2019 (COVID-19) outbreak. This crisis has evidenced a fragile reality of the SOHO in Europe, and SoHO organisations were placed under unprecedented stress, putting their capacity to provide the adequate care needed at risk. Beyond COVID-19 crisis, in the recent years, European countries have experienced several other crisis, which caused the disruption of routine activities of Procurement Organisations (PO) and Blood and Tissue Establishments (BE/TE), affecting temporary the ability to assess and evaluate donors, or prepare, issue and distribute Blood, Tissues and Cells (BTC) at local, regional or national levels. EGALiTE (European Group for Accreditation and Liaison of Blood-Tissues and Cells Establishments) aims to promote the harmonization of practices among PO, BE and TE, encourage sustainability and collaboration among stakeholders and the implementation of strategies required to improve accessibility and sufficiency of SoHO at European level. The outcomes of EGALITE aim to support the activities performed in Member States with distinct technical capacities by: 'Ä¢ Establishing an European Accreditation Program for HSC registers, PO, BE/TE 'Äì as a mean to achieve mutual recognition amongst SoHO organisations; 'Ä¢ Develop an efficient database of resources (BTC, facilities, activities and innovative techniques, etc.) which will be used to design sufficiency plans and promote the collaboration among professionals and CAs, to ensure an adequate supply of BTC in the different MS; 'Ä¢ Provide contingency plans to assist the responsible persons in the decision making process during crisis; 'Ä¢ Implement a Technical Assistance Program to assist the implementation of good practices and optimization of activities in the different Member States.",,2024,BANC DE SANG I TEIXITS,1080163.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2022 +P23543,960747,3D image-based search engine and triaging software for lung CTs to improve radiology workflows,"Radiology is struggling. Exponentially increasing quantities of data make it difficult to index and search for relevant information when it's needed most. Radiologists' workload is also rapidly increasing, exacerbated by the global radiologist shortage. What's more, new treatments require more complex diagnoses. When faced with a difficult case, radiologists must currently wait to discuss with colleagues, consult reference books or guess search terms in text-based resources. This frustrating, time-consuming process leads to delays, missed findings and high overtime expense. contextflow develops deep learning-based tools to improve radiology workflows, saving time while increasing reporting quality. SEARCH is a 3D image-based search engine designed to help reduce search time for difficult cases. Lung diseases are particularly hard to diagnose; they are characterised by the combination and distribution of 40 anomalous patterns observed in lung CTs. SEARCH can already detect 19 disease patterns (competitors only 1-3), instantly linking a 3D image to reference cases with similar findings, case statistics and reference information necessary for differential diagnosis. TRIAGE is a separate tool that automatically detects disease patterns in scans so that doctors quickly identify time-critical patients. contextflow aims to reduce the time radiologists spend searching for information, allowing for both faster and higher-quality diagnostics. The EIC project will complete the remaining technical and business development activities before product launch: developing methods to detect lung diseases based on the anomalous lung disease patterns already detected by the software; and identifying signatures indicative of diseases in medical data to support personalised treatment decisions. As the coronavirus (COVID-19) is characterised by distributions of anomalous patterns that contextflow already detects, developing disease detection for COVID-19 infections is a high priority.",,2022,CONTEXTFLOW GMBH,1447047.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Austria,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +P23545,101005177,COVID-19 infections - Remote Early Detection,xxx,,2022,UNIVERSITAIR MEDISCH CENTRUM UTRECHT,10743072.48,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,,,2020 +P23546,101133273,Vax-Action: tackling effectively vaccine hesitancy in Europe,"Vaccine hesitancy is the delay in acceptance or refusal of vaccines despite their availability. It is not a new problem, but a problem increasingly being recognized globally, and poses an academic and political concern. Its main implication reflects in lower-than-expected vaccine uptake rates. Two main strategies to lessen vaccine hesitancy stand out: targeted at people at large (communication campaigns, fact-checking, etc.) and at frontline healthcare workers, FHW, (training, manuals, etc.). However, it is yet not clear what works well, for whom, when, and under which circumstances. VAX-ACTION aims to support EU Member States and relevant stakeholders to implement a combination of tailored, evidence-based interventions aimed to reduce vaccine hesitancy. It addresses the need to understand what type of interventions are now available, which are effective, how to translate effective interventions to new contexts, and to explain the unsuccessful ones to create opportunities for learning and redesign. VAX-ACTION key relevance is to design and implement interventions and recommendations built on sound theory, existing evidence, and best practices of principles in health evaluation. We use a co-design model to engage FHW, and targeted populations (i.e., newly arrived migrants, hesitant parents, people of low socio-economic status) to tailor interventions regarding recently approved vaccines such as Covid-19 and mpox, and long-standing vaccines in national vaccination programmes. Interventions will be conducted in target regions in Portugal, Italy, France, Romania, and Czechia. Interventions are designed and evaluated in two settings per target region (the intervention group and control group, 1:1). The recommendations for embedding improvement and change will be prioritised along with tailored dissemination and evaluation strategies. This will support scale up and translation to other member states, WHO European Region members and other countries.",,2026,UNIVERSIDADE NOVA DE LISBOA,1511058.28,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Internally Displaced and Migrants | Other,Health Personnel,Clinical,Unspecified | Not applicable,Coronavirus | Poxviridae,,,,,,,,,COVID-19 | Mpox,European Commission,Europe,Europe,Europe,Unspecified,,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations,Portugal,,"Policies for public health, disease control & community resilience",Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2023 +P23547,101016174,Lab to Fab development of air decontamination system for protecting health practitioners against COVID19,"The CleanAir project relates to the application of an innovative and novel geometrically extended electrode design to be integrated in air ionizers. This innovative electrode design has already been pre-tested successfully for efficient electrostatic disinfection and particle removal from air. Contrary to other air ionizers available on the market it does not produce any harmful substances such as ozone or NOx because corona discharges will not occur. As a further innovative step, the electrode can be manufactured in different and much larger sizes and various 3D geometries to make them suitable to different needs from the medical end consumers for mounting them in examination and treatment rooms. The final product will be easily adaptable to be used efficiently in rooms of different sizes and heights. The aim of the CleanAir project is to develop this technology to a market-ready and CE mark certified device for series production for protecting health practitioners and their patients against COVID-19 infections. Market ready devices for three application areas will be preferentially developed in the project: for dental treatment rooms, for medical doctors offices and for patients rooms in a hospital. The project will prepare all required documentation, marketing information, customer portfolio and a sales and detailed business plan for being ready after the end of the project to start the series production and commercialization phase.",,2023,VILLINGER GMBH,2694802.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Austria,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P23548,101046133,Integrated Services for Infectious Disease Outbreak Research,"The ISIDORe consortium, made of the capacities of European ESFRI infrastructures and coordinated networks, proposes to assemble the largest and most diverse research and service providing instrument to study infectious diseases in Europe, from structural biology to clinical trials. Giving scientists access to the whole extent of our state of the art facilities, cutting edge services, advanced equipment and expertise, in an integrated way and with a common goal, will enable or accelerate the generation of new knowledge and intervention tools to ultimately help control SARS CoV 2 in particular, and epidemic prone pathogens in general, while avoiding fragmentation and duplication among European initiatives. Such a global and interdisciplinary approach is meant to allow the implementation of user projects that are larger, more ambitious and more impactful than the EU supported transnational activities that the consortium is used to run. Our proposition is ambitious but achievable in a timely fashion due to the relevance and previous experience of the partners that we have gathered and that have complementary fields of expertise, which addresses the need for an interdisciplinary effort. Leveraging all these existing strengths to develop synergies will create an additional value and enhance Europe capacity for controlling emerging or re emerging and epidemic infectious diseases, starting with the COVID 19 pandemic. Such a global and coordinated approach is consistent with the recommendations of the One Health concept and necessary to make significant contributions to solving complex societal problems like epidemics and pandemics.",,2025,EUROPEAN RESEARCH INFRASTRUCTURE ON HIGHLY PATHOGENIC AGENTS,23728445.12,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,,,2022 +P23549,101104880,Experimental assessment of wildlife viruses emergence potential through systematic characterization of human cell tropism,"Emerging viruses pose a tremendous threat to human health and economy, as dramatically shown by the ongoing COVID-19 pandemic. Most emerging viruses are zoonotic, meaning that they can be transmitted between animal species and humans. Although it was estimated that more than one million viral species exist in the two main reservoirs of zoonotic viruses (mammals and birds), only a few hundred are known to infect humans. This means that the majority of wildlife viral species will likely not cause major outbreaks in the human population, but that many potentially human-infective viruses are lurking in nature. Although large-scale metagenomic studies allowed the identification of thousands of new viral species, functional data, including their ability to infect human cells, are often missing. Previous work has examined the human cell tropism of a fraction of wildlife viruses, but no systematic analysis of the factors involved in viral entry has been undertaken. In this proposal, we will use synthetic biology, experimental virology and viral evolution using a large number of human cell lines to implement a high throughput characterization of wildlife viruses' tropism. We will first test whether wildlife viruses'Äô envelopes from diverse viral families can mediate infection of a large panel of human cell lines. Comparing available transcriptomic data of susceptible and non-susceptible cell lines, we will identify novel wildlife viruses'Äô host entry factors. Finally, using experimental evolution, we will investigate how viral envelope natural selection and diversification impact the use of these newly identified entry determinants. Overall, this project should improve epidemic preparedness by identifying viral species or variants at higher risk to infect humans, as well as host factors participating to viral entry, which are potential targets for the development of antivirals.",,2025,UNIVERSITAT DE VALENCIA,180191.17,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2023 +P23550,101027987,Multiscale study of the interactions between corona viruses of various pathogenicity and cell membrane components in the early stages of virus entry,"Coronaviruses (CoV) have been responsible for several severe viral outbreaks culminating in the current global pandemic. However, some viruses of this family are widespread and only cause mild conditions, like the common cold. The origin of the significant variation in the severity of the CoV-related diseases is still poorly understood. Recent studies have suggested that the strength of the interaction between the virus and the cell surface during the early stages of virus entry could play an important role. CoVs attachment to the plasma membrane is mediated by the specific interaction between the viral spike glycoprotein (CoV-S) and receptors found on the cell surface. In addition, several CoVs have been shown to interact with the cellular glycocalyx during the early attachment to the cell surface. In this proposal, I describe the study of the early entry mechanism of CoV-SARS, CoV-SARS2, and hCoV-NL63 which all target the same cellular receptor, angiotensin-converting enzyme 2, while strongly varying in their pathogenicity. The study focuses on the dynamics, kinetics and strength of the interaction of these viruses with the cell surface. It employs an incremental approach, from the study of the bond between individual CoV-S and single membrane components to multivalent interactions between the virion and the cell surface. A wide array of biophysical (e.g. single-particle tracking, and optical tweezer) and biological (e.g. viral pseudotypes) techniques are used, combining the host'Äôs and my expertise. This multidisciplinary project will result in a unique and comprehensive characterisation of the interactions taking place during CoV-entry, it will elucidate the difference between viral species, and it will give insights into the origin of the observed differences in pathogenicity. In addition, this work will strengthen and expand my experience and network in the virology and biophysics fields, significantly improving my career prospects as an independent researcher.",,2024,UMEA UNIVERSITET,205281.64,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS) | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23551,101047223,Nanoscale virus imaging X-ray microscope based on incoherent diffraction,"Coronavirus disease (COVID-19) is an infectious disease that emerged in late 2019. By March 2020, the outbreak was declared a devastating pandemic and¬†clearly illustrated the threat that viruses pose to our society. The characterization of viral structures¬†and the identification of key proteins involved in each step of the cycle of infection are crucial to developing treatments. Yet imaging single viruses can only be performed in a few specialized centers in Europe, while every hospital could benefit from it. ¬†NanoXCAN proposes to develop a tabletop¬†virus imaging X-ray microscope, with foreseeable impact as revolutionary as the invention of super-resolved fluorescence microscopy, paving the way towards¬†determination of structure and dynamics of matter to a large community. For this purpose, we will develop an original digital laser that delivers, on a daily operation, subwavelength focusing, reaching relativistic intensities at MHz repetition rates. This will be used to create a nano-source of hard X-rays from the Kalpha plasma emission of metallic nano-targets¬†at an average power comparable to that of a synchrotron beamline.¬† We will capitalize on this high brilliance, high¬†average power hard X-ray source to perform lensless nanoscale biomedical imaging based on recent findings in incoherent imaging and machine learning. All these¬†ingredients will create a unique nanoscopy platform that our consortium will illustrate by imaging a single virus. In the future, our X-ray IDI microscope could help¬†to study mechanisms involved in viral infection and antiviral design. X-rays have the advantage of performing in-situ non-destructive and non-invasive imaging over competing techniques. NanoXCAN will create a transformative positive effect on our economy and society by proposing this new technology for single¬†virus imaging.",,2026,IST-ID ASSOCIACAO DO INSTITUTO SUPERIOR TECNICO PARA A INVESTIGACAO E O DESENVOLVIMENTO,3909728.55,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Portugal,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23552,190144923,Fighting Large-Scale Untreated Infectious Diseases with Innovative Treatments,"Founded in 2020, Meletios is developing innovative antiviral strategies to treat existing and emerging acute viral infections. Among those, our lead program, presented at the EIC Accelerator, is an oral Host-Directed Agent targeting cell mechanisms hijacked by viruses. By acting on cell membrane'Äôs fluidity, our antiviral strongly limits cell internalization and intracellular trafficking of viruses. This approach could be effective against broad virus families, conferring our molecule with an advantageous broad-spectrum effect, a key strategy to boost our capacities to ward off outbreaks. Moreover, our agent has immunomodulatory effects enabling to efficiently manage viral diseases by preventing excessive immune system reactions. We will perform an accelerated development process as our molecule has already proved it safety in humans. COVID-19 will be the first demonstrator of our molecule'Äôs efficacy, before targeting diseases induced by other coronaviruses, influenza, flaviviruses.",,2024,MELETIOS THERAPEUTICS,2675000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P23553,101060448,At the Margins of Equality: A Theory of Vulnerability to Social Exclusion,"The COVID-19 pandemic has exposed our shared vulnerability to isolation, serving as a reminder that relations of marginalization and exclusion constitute significant obstacles to the achievement of a society in which everyone can fully participate and stand in relations of equality with each other. Moreover, empirical research has shown that marginalised individuals are being disproportionately disadvantaged by the Coronavirus emergency in several ways: they are the target of stigmatization and discrimination. And, although they are more likely to experience mental health issues and are typically exposed to serious health risks, they are not provided access to the same degree of medical care as other members of society. The current socio-political state of affairs, then, vividly illustrates how persons' vulnerability to social exclusion is one of the most pressing social justice challenges that liberal democracies must face. Building on my previous research on the justification and the value of equality, in this project I will contribute to the Horizon Europe strategic plan towards ""creating a more resilient, inclusive and democratic European society"" by developing the first-ever comprehensive liberal egalitarian theory of vulnerability to social exclusion in analytical political philosophy. This theory will define the rights that marginalized individuals have to be fully included as equals in society and identify the social arrangements that the state ought to put in place in order to ameliorate their social condition. In our current pluralist and diverse societies the call for social equality is ubiquitous but its precise meaning is contested. By providing an account of what shape equality takes when applied to socially marginalized groups, this research will thus fill an important theoretical and normative gap when thinking about what a just society owes to its most vulnerable members if they are to be considered and treated as equals.",,2024,UNIVERSITAET HAMBURG,168631.59,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23556,962036,Treat severe cases of infection at COV with XAV-19,"This is letter of Intend to address the COVID-19 request by the European Union for the EIC accelerator. We have unique platform to develop polyclonal antibodies to address complex immune response such as the current pandemic. Over the course of the last 4 years we have developed pipeline of unique immunotherapies addressing various health needs, from transplantation to infectious disease. The coronavirus epidemic was developing we explored the possibility of developing treatment. Unfortunately given the time constraint and short notice we do not have the time to fully develop complete application we are submitting our response the current health need. We like the opportunity to further developed our plan with more time.",,2022,XENOTHERA,2551927,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P23558,101059483,Biodiversity Conservation to Mitigate the risks of emerging infectious diseases,"Biodiversity loss in hotspots of biodiversity is, among other socio-ecological factors, key to understand, prevent and react to future pandemics. However, despite this knowledge, the current COVID-19 crisis highlights the limitations of the implementation of One Health approaches. A main limitation is the lack of context-adapted solutions that stakeholders could easily implement on the field. To overcome this, BCOMING will build on past international projects to co-construct innovations with all stakeholders of biodiversity hotspots to reduce the risk of infectious disease emergence through biodiversity conservation and disease surveillance strategies. The activities of the project will be implemented in Europe and three tropical biodiversity hotspots in Southeast Asia, West Africa and the Caribbean and will have the following expected impacts: - BCOMING will lead to a better understanding of the mechanisms underlying the impact of biodiversity on the risk of infectious disease emergence - Participatory tools developed will facilitate the design of context-adapted biodiversity conservation and restoration strategies that reduce zoonotic risk - The surveillance strategies and pathogen detection tools developed will improve the capacities to detect emergences and stop future epidemics before they can turn into pandemics The consortium constitutes a strong multi-actor group of partners with a history of successful cooperation including academics from biomedical, environmental and social sciences, private companies, NGOs, local and international stakeholders who bring together the wide range of disciplines and expertise required to reach all the expected outcomes of the call. The embedment of BCOMING in the Prezode initiative will help to scale up the project innovations and disseminate cutting-edge socio-economic environmental strategies.",,2026,CENTRE DE COOPERATION INTERNATIONALE EN RECHERCHE AGRONOMIQUE POUR LEDEVELOPPEMENT - C.I.R.A.D. EPIC,5048607.3,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,Animal and environmental research and research on diseases vectors,,2022 +P23560,101103332,SCALING UP CAPACITY TO SUPPORT CONDUCT OF CLINICAL TRIALS IN THE EAST AFRICAN COMMUNITY,"The East African Community (EAC) has experienced significant increase in volume and complexity of clinical research driven by epidemics of emerging and remerging infectious diseases such as HIV, Ebola and COVID-19, requiring expertise in scientific and ethical review and conduct of research and a robust and pragmatic research regulatory framework. The overall goal is to strengthen scientific and ethics capacity in EAC for high quality research review, conduct and oversight, at international standards. The specific objectives are: 1. To train NRRA personnel, REC members, researchers and clinicians on scientific and ethics review and conduct of research with emerging and complex study designs including adaptive platform trials 2. To train NRRA personnel and REC members on oversight, monitoring and pharmacovigilance of clinical trials and 3. To train NRRA personnel, REC and research administrators on personal effectiveness and leadership skills (PELS) to manage the increasingly complex research processes. Methods: We will implement this project within a consortium of research scientists from the six partner states collaborating with the EU partner, with the East African Health Research Commission as the strong nucleus for coordination and dissemination of results. The project will be hosted at the Infectious Diseases Institute (IDI), where within a previous NIH funded program (5G11 TW011309-01) we built capacity for REC members, researchers and REC administrators for 7 RECs in Uganda, with significant improvement in knowledge, PELS, quality and turnaround time of research review and researcher satisfaction. This proposal fits within the scope of GH-EDCTP3-2022-01-05 call, whose aim is to strengthen clinical research capacity and improve efficiency of the regulatory environment for effective development, delivery and uptake of new and improved safe health technologies and rapid response to emerging epidemics guaranteeing international standards and attainment of SDG3.",,2026,EPICENTRE,642000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,Research on Capacity Strengthening,Cross-cutting,2023 +P23561,101130006,Biomimetic Membranes for Organ Support,"Acute respiratory distress syndrome (ARDS) is currently seen in huge numbers of patients worldwide due to the COVID-19 pandemic, but also before that, respiratory diseases were the third largest cause of death in the EU. Current therapy for respiratory failure includes mechanical ventilation and extracorporeal membrane oxygenation (ECMO) both associated with high morbidity and mortality. In ECMO devices the functionality of the lungs tissue membranes that are responsible for gas exchange during breathing is usually taken over by bundles of synthetic cylindrical hollow fiber membranes. Geometries and transport characteristics of standard hollow fiber membranes are not suitable for re-building the structurally complex and dynamic contracting microstructure of the mammalian lung and consequently, artificial devices to assist/replace respiration still face major limitations in size, flow characteristics and hemocompatibility that impede the development of efficient intracorporeal devices. In BioMembrOS, we want to follow a groundbreaking new biomimetic approach, and replicate main characteristics of the most effective respiration found in vertebrates, mainly birds and fish, in order to develop membrane structures that will serve as key elements for a novel generation of artificial respiration devices. To reach this goal, we will a) optimize geometry of the membrane structure by mimicking microstructure of the gills of fish to increase outer surface per membrane area, mimicking globular shape of the gas transporting inner lumen and interconnected arrangement of membrane fibers of avian respiration; b) design and control flow characteristics and boundary layer applying √鬺PIV experimental flow investigations and structural design optimization; c) design and synthesize bi-soft segment polyurethane membranes with increased hemocompatibility and gas permeability with phase inversion; and d) verify and benchmark the boosted mass transfer capabilities by in-vitro blood tests",,2027,TECHNISCHE UNIVERSITAET WIEN,3187335.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Other,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,Clinical characterisation and management,"Supportive care, processes of care and management",2024 +P23562,101136380,BreathForDx: Establishing Exhaled Breath Aerosol (XBA) sampling for diagnosis and screening of respiratory infections,"Respiratory infections resulted in >7 million deaths in 2020 and were responsible for 7 of the last 9 pandemics, causing trillions of 'Ǩs in economic losses. Despite the importance of early detection for individual health and pandemic control, flawed sampling methods for respiratory infections limit the impact of highly-sensitive diagnostics. BreathForDx'Äôs will tackle this problem by establishing exhaled breath aerosol (XBA) as an evidence-based, non-invasive sample for simple detection of respiratory infections that can be undertaken at all levels of care. We will achieve this by developing and optimising two innovative, easy-to-use and scalable XBA sampling devices and generating evidence for their use in diagnosis and screening (for early diagnosis and transmission control). We will use different model pathogens that have caused epidemics and pandemics globally 'Äì SARS-CoV-2, influenza, and tuberculosis (TB) 'Äì and we will generate data on the feasibility of multiplex detection of respiratory pathogens in XBA samples, the adaptability to novel pathogens applying viral metagenomics, and point-of-care testing with lateral-flow assays. We will assess the sampling efficiency of the novel devices against a benchmark Respiratory Aerosol Sampling Chamber and evaluate performance, feasibility, and acceptability, in comparison to the current standard of sampling in multi-country clinical studies of diagnosis and screening. Impact and economic modelling will inform the implementation potential of the novel devices for the different use cases and help assess trade-offs. The project will leverage innovation in bioaerosol and material science, as well as the multidisciplinary (including academia, industry and NGOs) consortium'Äôs track record of delivering transformative diagnostic innovation. We envision that a single breath sample enables accessible and accurate detection of highly transmissible respiratory infections, thereby improving both individual and population health.",,2028,UNIVERSITATSKLINIKUM HEIDELBERG,7290153.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2024 +P23563,101094804,Establishing Exhaled Breath Aerosol (XBA) sampling for diagnosis and screening of respiratory infections,"Respiratory infections resulted in >7 million deaths in 2020 and were responsible for 7 of the last 9 pandemics, causing trillions of 'Ǩs in economic losses. Despite the importance of early detection for individual health and pandemic control, flawed sampling methods for respiratory infections limit the impact of highly-sensitive molecular diagnostics. BreathForDx'Äôs overall goal is to tackle this problem by establishing exhaled breath aerosol (XBA) as a novel, evidence-based sample for respiratory infections in three use cases: diagnosis, screening, and antimicrobial resistance, using tuberculosis (TB) as a model infection. The project will leverage innovation in bioaerosol and material science, as well as the multidisciplinary (including academia, industry and NGOs) consortium'Äôs track record of delivering transformative diagnostic innovation. More specifically, we will optimise an innovative, easy-to-use, scalable XBA sampling device, and compare it to a face mask sampling device coupled with rapid molecular detection in three clinical studies. We will evaluate the XBA sampling efficiency of these devices using the Respiratory Aerosol Sampling Chamber as a benchmark. Next, we will assess performance of the devices for diagnosis of TB and drug-resistance among symptomatic patients in a high burden EU country. In parallel, we will assess the feasibility of multiplexing XBA samples for multiple respiratory pathogens (i.e., TB, influenza, SARS-CoV-2) in a screening use case. Accuracy and feasibility data will be complemented by data on acceptability and usability, as well as cost-effectiveness and impact modelling to inform the implementation potential of the novel devices across different use cases. We envision a world in which a single breath sample, coupled with point-of-care molecular diagnostics, enables accessible and accurate pathogen and resistance detection of highly transmissible respiratory infections, thereby improving both individual and public health.",,2026,UNIVERSITATSKLINIKUM HEIDELBERG,2478020.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2024 +P23564,101057596,"A holistic approach in patient management and epidemic surveillance through convergence of diagnostic technologies, capacity building and stakeholder engagement","Research on Poverty-Related Diseases (PRDs) in sub-Saharan Africa suffers from major technological and non-technological challenges that prevent high quality healthcare to reach many areas. Not only their performance, but also the affordability, manufacturability, suitability for Low- and Middle-Income Countries (LMICs) and deployment of the (few) available diagnostics are main barriers to ensure good quality of healthcare in sub-Saharan Africa. The HoliCare project aims to tackle such challenges from a holistic perspective, by bridging the gap between technological excellence, available infrastructures, capacity, and local uptake of new technologies. We have chosen to work with lower respiratory infections as a blueprint for our new approach due to their huge clinical and socioeconomic impact, and relevance to the SARS-CoV-2 pandemic. Technology-wise, we propose a 2-tiered, digitally interfaced diagnostic approach that will start in the field using multiplexed lateral flow tests for rapid screening and triage, followed by a referral to a hospital (when needed) and a follow-up detailed diagnosis using a POC-Instrument performing simultaneous nucleic acid amplification (LAMP) for pathogen identification and immunoassays for host biomarker quantitation. Digital and manufacturing infrastructures will encompass these technology innovations to ensure future local product development. Quality controlled biobanks will be developed for executing reliable clinical studies. Training and human capital investment will be achieved by focussed and high-level training activities. Adoption and implementation activities will pave the way for the proposed diagnostic solutions to be successfully deployed, fitting the purpose of the local populations. Our developments will be scalable, adaptable and transferrable to other diseases and national (eco) systems, aiming to contribute to the improvement of healthcare delivery in sub-Saharan Africa.",,2025,KUNGLIGA TEKNISKA HOEGSKOLAN,5857774,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Health Systems Research","Diagnostics | Disease pathogenesis | Supportive care, processes of care and management | Health service delivery | Medicines, vaccines & other technologies",2022 +P23565,101113404,"Enhancing clinical microbiological whole-genome sequencing capacity as well as analysis, management and sharing of respective sequencing data in Sweden","The project aims to enhance the national capacity of whole genome sequencing within clinical microbiology by extending the clinical microbiological labs'Äô ability to sequence more pathogens and enhancing the national processing of the data downstream at the Public Health Agency of Sweden (PHAS) for data and results dissemination. The transition from conventional methods for the characterisation of pathogens to whole genome sequencing is further to be promoted by supplying an advanced IT infrastructure for analysis, management and sharing of respective sequencing data and results at the national level, as well as enabling cross-border information sharing to other public health agencies in EU. The IT platform, currently being developed at the PHAS, has a modular approach enabling the implementation of additional pipelines for automated analysis of many pathogens. Sequencing data will be stored and managed using on-premise cloud infrastructure, and APIs facilitate sharing of specific data to relevant parties through an open data approach (open as possible, closed as necessary). Recently established IT hardware and infrastructure at the PHAS, laboratory instrumentation and workflows at the regional labs, and ongoing development of the bioinformatics and data management platform at the PHAS represent the foundation upon which this project will build. Focused on SARS-CoV-2 during the last two and a half years, WGS is now to be implemented at a larger scale for additional pathogens from the lab and data perspective. Ultimately, the goal is to strengthen the implementation of WGS in clinical microbiology to elevate this technique into a routine application and ensure preparedness for future health threats. For this, the use of established networks, collaboration and communication efforts is how the project's impact is ensured.",,2025,FOLKHALSOMYNDIGHETEN,1090000,Bacteria | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Sweden,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P23570,101113387,Genomic surveillance of selected infectious diseases in the Czech Republic,"The project aims to improve the capacity of National Reference Laboratories (NRLs) in the National Institute of Public Health (NIPH) in Prague for genotypic characterization of a range of human pathogens (especially SARS-CoV-2 and other respiratory viruses, bacterial pathogens with cross-border threat potential, including antibiotic-resistant bacteria) with public health significance. The whole genome sequencing (WGS) is currently the state-of-the-art method for detailed characterization of microorganisms, as it provides a complete description of the genetic information of a given microorganism and its objective outputs allow immediate interlaboratory comparisons at the national and international levels. The aim of the project is to improve the availability of genomic surveillance of communicable diseases in order to identify and characterize specific determinants for the description and identification of clonal lineages with significant potential for their spread. The project responds to the need to ensure genomic surveillance within European structures (specifically the ECDC). Without the implementation of routine genomic surveillance, monitoring and addressing national and cross-border threats of infectious diseases and antibiotic resistance is not possible. This proposed project directly builds on the previous project that was granted under ECDC procedure Grant/2021/PHF/23776. This project builds on Grant number ECDC/HERA/2021/004.ECD.12218.",,2025,STATNI ZDRAVOTNI USTAV,1351821.1,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Czech Republic,,Epidemiological studies,Disease surveillance & mapping,2022 +P23571,101040383,A binary sensor with single-molecule digit to discriminate biofluids enclosing zero or at least one biomarker,"Biomarkers are measurable indicators of a particular disease state of an organism. There has been an increasing demand for diagnostic markers, enabling reliable and non-invasive screening of peripheral biofluids. It is also established that a universal screening against life-threatening diseases, such as cancer, or infectious disease outbreaks, can be accomplished only by combining genomic and protein marker-based tests. The NoOne project aims at conceiving, engineering, fabricating and validating a ground-breaking platform based on a single-molecule binary bioelectronic sensor, capable to reliably discriminate biofluid samples enclosing zero biomarkers from those containing just one. The technology can be used for ultimate binary sensing of both proteins/peptides and genomic markers to enable the reliable screening of diseases such as cancer as well as viral and bacterial infections. The NoOne binary platform is designed to be portable, cost-effective, easy to operate and with a time-to-results within one hour; hence it is the ideal candidate for point-of-care applications. The prototype will enable clinicians, phytopathologists or veterinaries, to identify the set of samples that are totally free from a protein, peptide or genomic marker as well as from a pathogen (virus or bacteria), from those enclosing at least one with a confidence level of 99%. This makes the NoOne platform the best performing ever in enabling a fast, highly reliable, cost-effective identification of the subset of biological samples belonging to the potentially diseased part of a population. This is of paramount importance for predictive screening of humans, plants or animals. NoOne will demonstrate its effectiveness in key relevant applications such as the binary detection of pancreatic cancer biomarkers, SARS-CoV-2 virus, the Xylella Fastidiosa bacterium and the assay of post translational peptides evidencing the phosphorylated forms regulating crosstalk with oncogenic signalling pathways.",,2027,UNIVERSITA DEGLI STUDI DI BARI ALDO MORO,2774532.69,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Italy,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23572,101084097,HEALTHY ENVIRONMENTAL-FRIENDLY AND RESILIENT FARM TO FORK,"In spite of the huge number of pathogens and diseases, the number of 'Äútransmission channels'Äù or 'Äútransport routes'Äù for microorganisms to enter in a farm or any other Farm2Fork facility is indeed limited to just nine. Tracing or monitoring transport of a single or a few microorganisms using a particular channel will provide valuable information on the channel itself and therefore on the transport effectiveness for the whole set of microorganisms using that particular channel. HE-FARM will develop and validate a methodology -based on experimental assays and tests in lab & operational env- to assess and predict transport-channel resolved biosecurity and simultaneously increase maturity of several disruptive novel techs. A software/APP will be created to help with these procedures and proposed as a draft for a future EN standard. Prototypes of novel technologies for biosecurity will additionally be developed and validated in operational environment -including extensive and intensive cow, pig, chicken, turkey, sheep and snail farms, a slaughter and meat preparation plant and trucks: Fast Integrated air-borne virus smart detector (PRRS and Avian Flue but easily extendable to other virus with an enormous like African Swine Fever whose early detection in air in minutes will have an enormous impact) Sanitization by low-toxicity biocides & dynamic aggregation. Low-toxicity insecticides & repellents & dynamic aggregation application & Env-Friendly Insect and Arachnids barrier and prevention techs. Rapid Vehicle decon. station. Biosecure & Env-Friendly Hall & Heat Venting and Cooling. Portable Low-cost test-device for fast measuring microbiological metabolism. Cold plasma farm water sanitization. Usage and training procedures and manuals & assessment of performance method. Finally at least other 3 biosecure techs externally provided selected in an open call will be experimentally tested. Comm. & dissemination include liaising with authorities like EFSA and OIE.",,2025,UNIVERSIDAD DE ALCALA,4949860.41,Animals | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P23576,101080024,Open Platform for European Networking and Repurposing of Oncological Assets and Drugs,"Despite technological advances, the productivity of the pharma industry and the efficacy of cancer drugs appear to be declining, requiring time and cost unsustainable in the long term. The repurposing of drugs (DR) already on the market or in late clinical stages is an increasingly promising strategy for developing novel therapies, especially cancer treatment. Serendipitous DR has recently been used in the early stages of the SARS-CoV-2 pandemic by front line health practitioners who were under pressure to find novel therapies fast as they attempted to save patients and help relieve the considerable stress on national healthcare systems. But serendipitous DR is not very efficient and in the case of cancer field-testing a very large number of possible drugs is not a feasible strategy. The aim of the NEWROAD project is to develop an EU-wide capability for Systematic Drug Repurposing (SDR), meaning the ability to identify with a high degree of predictive accuracy novel therapies for any disease of interest and at a future stage any combination of diseases. To achieve this NEWROAD will develop an open, collaborative in silico platform for the repurposing of drugs in oncology based on Augmented Intelligence (AuI) architecture layered on top of Artificial Intelligence (AI) algorithms, initially targeted at rare and paediatric cancer research. The platform is designed with easy-to-use yet powerful AI features that aim to encourage researcher engagement and collaboration. NEWROAD will be deployable on a network of high-performance computers and in the cloud, and will leverage data provided by hospitals, clinics, pharmaceutical companies etc. in the European Community. The NEWROAD platform will therefore have a triple function: 1. The development of novel therapies based on the repurposing of drugs (initial focus on oncology); 2. the sharing of clinical data by entities in the European Community; 3. the development of an open collaborative platform for SDR.",,2025,UNIVERSITA DEGLI STUDI DI SALERNO,971383.05,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2022 +P23577,101057597,"ANTIVIRAL, ANTIBACTERIAL & ANTIFUNGAL NANOCOATING PLATFORM","The NanoBloc consortium of 4 leading universities & institutes, and 5 companies (3 SMEs & 2 large enterprises) will develop & upscale (from TRL3 to TRL6) new all-European antimicrobial, antifungal & antiviral coatings made by industrially scalable, green technology suitable for application on a variety of substrates- porous filter materials (air filtration units, face masks), textiles (protective clothing, mattress covers, aprons, wallpaper), & on a variety of high-traffic solid surfaces (door knobs, handles, handrails, sanitaryware-taps, etc.). A research line will focus on thin coatings- <200 nanometers- deposited by Physical Vapour Deposition, formed by a glass and/or ceramic matrix (e.g. silica) capable of incorporating silver or other metal nanoparticles, which can be applied on countless substrates. These coatings allow a gradual release of ions without dispersing the nanoparticles in the surrounding environment & have demonstrated their effectiveness toward proliferation of bacteria, fungi & viruses including respiratory syncytial virus, influenza virus A & with demonstrated virucidal effect towards SARS-CoV-2 on face masks. They can withstand temperatures up to 450 degrees celsius without altering their antimicrobial properties, thereby suited for thermal regeneration. In addition, the project will build on previous work in obtaining coatings effective against a range of pathogens using technologies such as UV cured lacquers, sol-gel and electrophoretic deposition. A key strength in our approach is in merging these research lines to obtain innovative products that will be brought to market by our industry participants. New knowledge generated in the project on antiviral mechanisms & coating durability in operating conditions, will be used to select the most suitable technology for each application & to develop and up-scale effective & durable biocidal/virucidal coatings to relevant demonstrators with no toxic effects for health & environment.",,2025,POLITECNICO DI TORINO,6128303.02,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Therapeutics research, development and implementation",,2023 +P23583,101065909,Whole brain visualisation of the neuroinflammatory response during acute neurotropic flavivirus infection and its implications for virus-induced neurodegeneration,"Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese Encephalitis Virus (JEV), West Nile Virus (WNV) and Zika Virus (ZIKV) can enter and infect the central nervous system, potentially leading to lethal encephalitis. Furthermore, survivors often suffer from chronic neurological complications, most likely due to virus-induced neuronal death and immune-related pathology. The past decade, the notion that neurotropic virus infections cause changes to specific neuronal populations, driving accelerated brain ageing and neurodegeneration has become an emerging concept. However, the interplay between virus infection, inflammation, neuronal death and neurodegeneration remains unravelled. In this project, I propose to investigate virus-induced neuroinflammation and its effect on pathways underlying neurodegeneration with frontline imaging techniques. To do so, I will optimise ex vivo optical projection tomography (OPT) and positron emission tomography (PET) for neuroinflammation and tau tangles and develop accurate image-based quantification pipelines for the proposed markers. These will thereafter be applied to study the neuroinflammatory course in acute flavivirus infection and, to unravel the specific role of the microglia in infection and neuroinflammation. Finally, I will investigate the effect of infection and virus-induced neuroinflammation on induction of neurodegeneration, reflected the induction of tauopathy. Taken together, this project will lead to the development of advanced ex vivo imaging techniques to visualise neuroinflammation and virus-induced neurodegeneration and, will improve our understanding on how neurotropic flaviviruses drive the brain into accelerated ageing, thereby priming neurodegeneration.",,2024,UMEA UNIVERSITET,221370.16,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P23585,101086685,"Integrative, AI-aided Inference of Protein Structure and Dynamics","The life sciences community is living in exciting times. During the past year, Artificial Intelligence (AI), and in particular AlphaFold2, has contributed to advancing our understanding of protein behaviour by enabling structure prediction with accuracy comparable to many experimental techniques at a fraction of their time and costs. However, structures are only a piece of the puzzle. To understand the mechanisms underlying biological functions, we need to characterize the conformational landscape of proteins, the population of relevant states, and their pathways of interconversion. Furthermore, we need to determine the effect of the environment in modulating structures, populations, and pathways, as biological systems perform their functions in the complexity of cells rather than in the isolation of test tubes. None of these objectives can be achieved by AI structure-prediction methods alone. In this proposal we will leverage the PI'Äôs expertise in the field of integrative computational-experimental techniques to develop, apply, and disseminate bAIes, a modelling approach that will enable attaining these goals. bAIes will make synergistic use of AI structural models, experimental data, and molecular simulations driven by accurate physico-chemical models to characterize protein structure and dynamics. We will demonstrate how bAIes can solve biological problems that exceed the capabilities of AI approaches, such as the characterization of protein disordered regions and the determination of structure and dynamics in situ, with a particular focus on the SARS-CoV-2 spike protein. The outcome of this proposal will be a versatile, accurate and efficient method that will push the boundaries of what can be achieved with AI structure-prediction methods. bAIes will be implemented in the widely used PLUMED library, of which the PI is founder and core developer, thus enabling its application to a wide variety of systems and biological problems beyond those envisioned here.",,2028,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,3226052.5,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P23587,101109395,"Neurotropic flavivirus dsRNA-protein interface in humans, mosquitoes and ticks","Neurotropic flaviviruses Zika virus (ZIKV) and tick-borne encephalitis (TBEV) represent major emerging arthropod-borne viruses transmitted by two different vectors, either mosquitoes or ticks. In humans, they use cells of the immune system to spread throughout the organism and can lead to severe encephalitis. During their replication, viruses produce double-stranded RNA (dsRNA) structures which is not only a necessary by-product but also performs key regulatory functions and acts as a pathogen-associated molecular pattern recognized by the host innate immune response. However, viral adaptation to such divergent host cells and organisms and their immune response, especially in arthropods, is poorly understood. In this project, I propose to investigate and compare how neurotropic flaviviruses interact through their RNA in humans and arthropods. First, I will identify host factors involved in protein-dsRNA complexes using anti-dsRNA antibodies in a high-throughput proteomic approach from infected live arthropods and human models for immune and neuronal cells and compare the protein networks between each host. Second, I will select the most significant and relevant hits for a functional screening, further define the function of the best candidates that are either pro-viral or anti-viral, confirm their importance in most relevant models and characterize the molecular functions of the best candidates. Finally, I will identify the dsRNA structures and RNA species interacting with the best candidates, and determine the evolutionary pressure imposed on the viral genomes in each host. Altogether, this project will contribute to unravel the adaptation of neurotropic flaviviruses to their hosts throughout their cycles, both from a mechanistic and evolutionary perspective, help understand the role of the RNA in crossing species barriers and lay the grounds for new therapeutics and disease control strategies against viruses that represent an ever-increasing threat in Europe.",,2025,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,211588.2,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P23590,101101051,Phototherapy treatment for long-term COVID-19 patients,"As the number of COVID-19 cases grows worldwide, so does the number of those suffering from clinical parameters that last weeks to-months post initial recovery, termed long-COVID, with as much as 36.55% of survivors exhibiting long-lasting symptoms (e.g., weight loss, chest pain, cognitive and memory disorders, breathlessness) according to recent studies'Äîan estimated ~157 million long-COVID adult patients worldwide to date. Clearly, this growing health problem represents a modern global medical challenge. This challenge is compounded by a knowledge gap regarding the causes and prevalence of long-COVID, leaving no effective treatments. As noted by The Lancet: 'ÄúThe scientific and medical communities must collaborate 'Ķ and find effective treatments'Äù. Based on findings from my ERC grant, supported by other COVID-related reports, I propose to validate a UVB radiation (phototherapy) protocol for the treatment of long-COVID patients. Our findings indicate that phototherapy induces an immunological shift that counters that of the COVID phenotype: from T helper (Th) 1 cells, which stimulate inflammation and cell-mediated immunity, to Th2 cells, which promote humoral immunity. Phototherapy is also expected to address a range of reported respiratory, cardiovascular, neurological, endocrine and metabolic long-COVID symptoms. Our PoC entails both validating via a clinical trial the proposed treatment, through a strong collaborative framework with Maccabi Healthcare Services, Israel'Äôs second largest HMO, and conducting pre-commercialization steps to enable quick, easy dissemination on the global stage. Taken together, our value proposition is an effective, non-invasive, simple long-COVID treatment that can be implemented through already established phototherapy clinics worldwide, thereby offering immediate relief to long-COVID patients while simultaneously reducing the health and financial burden of severely overburdened health systems.",,2025,TEL AVIV UNIVERSITY,162000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Israel,,Clinical characterisation and management,Post acute and long term health consequences | Clinical trials for disease management,2023 +P23591,959886,COVID-19 ICU-CARE COVID-19 ICU-CARE - A ground-breaking ICU bed-side COVID-19 trachea flushing system that can cut healthcare costs and reduce COVID-19 spread between ICU patients and staff,"When the severely ill COVID-19 patients are admitted to the Intensive Care Unit (ICU) for respiratory support (breathing with the support of a mechanical ventilator), it is crucial that the upper airways of these patients are being suctioned many times daily to remove secretion and mucus, in order to prevent lung infections. If not removed efficiently, there is >50% likelihood of mortality. Unfortunately, the suctioning techniques today have 2 major limitations 1) it cant remove secretions efficiently and thereby preventing lung infections and 2) it induces a very high risk of COVID-19 spread amongst ICU patients and staff, as secretion is suctioned outside the patients body. AW Technologies aims to solve these problems with TrachFlush 'Äì a patented suctioning assist system. As an add-on to standard mechanical ventilation systems used in the ICU, TrachFlush automatically flushes ALL secretion out of the airways and has already shown to cut cost and to reduce contamination in a small feasibility study on general ICU patients. The aim of this project is to take TrachFlush to market and battle the COVID-19 outbreak. In collaboration with experts from 5 leading hospitals from Denmark, Italy, Holland and Spain, this COVID-19 ICU-CARE project concerns a large-scale clinical study to reach TRL 8 and aims to demonstrate: 1) a 90% efficient secretion removal and implicit reduction in lung infections, 2) a 90% reduction in ICU nurse workload and, 3) elimination of any contamination between patients and staff 'Äì on COVID-19 patients! When we reach these goals, we can help EU battle the COVID-19 outbreak. The business opportunity is huge. Our market is 'Ǩ3,6Bn and will reach 'Ǩ4,5Bn by 2025. Via a recently signed distribution agreement with an ICU ventilator manufacturer, we aim for rapid market penetration and a market share of 5,3%, a turnover of 'Ǩ100M, an EBITDA of 'Ǩ57M and additional employment of 22 people by 2025. We foresee a total budget of 'Ǩ1.7M for this project",,2021,AW TECHNOLOGIES IVS,1412163.82,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23592,101079001,BRAIN RESEARCH AND INTEGRATIVE NEUROSCIENCE NETWORK FOR COVID-19,"The Brain Research and Integrative Neuroscience Network for COVID-19 (BRAINN) will advance the research and innovation capacity of the University of Cyprus (UCY) as indicated in the 'ÄòWidening Participation & Strengthening the ERA'Äô Work Programme, by twinning with three advanced partners in brain research, Maastricht University (UM), King'Äôs College London (KCL), and Ghent University (UGent). Through networking activities, training and coordinated actions, BRAINN will develop an innovative applied neuroscience approach to characterise the effects of COVID-19 on brain health and to elevate the standards of assessment, diagnosis, prognosis and treatment of patients with mental health and cognitive problems due to COVID-19. The UM, KCL and UGent teams have complementary world-renowned expertise in neuroimaging, non-invasive neurostimulation and digitalised assessment methods, extensive research management experience and active interest in post-COVID research. Engaging these teams as partners will provide the required mentoring and training towards a focused and systematic approach to neuroscience research in a mutually beneficial manner to raise the research profile of UCY, as well as strengthen the research management and administrative skills of UCY staff. BRAINN will benefit all partners, as the standardisation of assessment and treatment protocols will expedite data collection and will safeguard the sustainability and future expansion of the network. Through interdisciplinary research and development of novel methods and technologies, BRAINN will contribute to personalised treatments, bringing both UCY and Cyprus to the scientific forefront. Additionally, BRAINN will address the brain drain challenge that has increased in Cyprus over the recent years and contribute to the reduction in the burden created by COVID-19. The knowledge and methodologies produced will extend beyond BRAINN, since they will be applicable to other conditions affecting brain health, even when COVID-19 is eradicated.",,2025,UNIVERSITY OF CYPRUS,1167740.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Cyprus,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P23593,101016065,COVID eXponential Programme,"COVID-X will bridge the collaboration divide between eHealth solution providers -with emphasis on lean startups and small and medium-sized enterprises (SMEs)-, and the healthcare professional system to fight COVID-19. The purpose is to boost an end-to-end agile validation programme of cutting-edge technology in three real-world clinical scenarios, located in hotspots of the pandemic: Italy, Spain and Sweden. The project will fast-track value streams between the two poles under consideration: 1) attract, invest and empower a community of European eHealth SMEs 'Äìthe beneficiaries of an acceleration program, selected by open calls- that will provide market-ready fast, cost-effective and easily deployable sampling, screening, diagnostic and prognostic systems and/or data-driven services and tools, already certified with -or close to receive- the CE marking (type 1 of the call); 2) actively involve some of the most relevant hospitals of Europe that have the resources, critical mass and ambition to scale-up their capabilities in the COVID-19 response; thanks to the support of an innovative data sandbox, released as an in-house asset of COVID-X, to facilitate access easily, uniformly and securely to various health data sources, and providing data services including Artificial Intelligence (AI)-based decision support systems, data security, visual analytics and intuitive dashboards capabilities. The project will invest dedicated efforts to enforce data privacy and security, ethical compliance and user acceptance. Besides a solid consortium to access world class startups/SMEs, deliver highly valuable technological & business services, provide an innovative data Sandbox with AI capabilities for COVID related services and access 3 piloting sites, COVID-X targets to attract +155 applications and select 31 to undertake through the COVID-X Programme, investing a total of 'Ǩ4.0mil in high impact solution providers.",,2022,F6S NETWORK IRELAND LIMITED,8427934.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,"Policies for public health, disease control & community resilience | Health Systems Research","Approaches to public health interventions | Medicines, vaccines & other technologies",2020 +P23594,101115188,a clinical research network to improve the management of Monkeypox virus disease,"The 2022 Monkeypox outbreak is unprecedented in scale and cases are still active in South America and starting to appear in South-East Asia. Many questions about Monkeypox virus disease remain unanswered to this day, particularly concerning the management of patients. MPX-RESPONSE aims to increase our knowledge of the monkeypox virus disease, to improve its therapeutic management and to further inform public health policies and guidelines through four Work Packages (WP). WP2 (MOSAIC) will assess clinical and virological outcomes of Monkeypox patients treated or not with antiviral drugs, focusing treatment on the most severe cases. WPs 3 and 4 will conduct randomized clinical trials (RCT) with the most promising antiviral therapy, tecovirimat, targeting patients in Europe (WP3-EPOXI) and globally in collaboration with WHO (WP4-UNITY); particularly in mild and moderate cases. A common primary outcome will be shared between the two RCTs and EPOXI will include additional objectives regarding pharmacological, immunological and virological outcomes in six to ten EU/EEA countries and fulfill in particular EMA requirements for treatment authorisation. A continuous systematic review and individual patient meta-analysis will summarize all randomized evidence of the interventions for monkeypox. Finally, the project will make sure that acquired knowledge is integrated into public health policies and guidelines and that adequate messages are shared with the general public and high-risk populations with the help of patients'Äô representatives and associations (WP1-COORDINATE). To accomplish these objectives, MPX-RESPONSE will build on the expertise and networks of multiples partners including Ecraid and EU-RESPONSE and will reinforce and broaden Europe'Äôs capacity to respond rapidly to public health emergencies.",,2026,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,12239998.98,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Poxviridae,,,,,,,,,Mpox,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Research for enhanced understanding of the disease | Promote improved understanding of the disease (including evidence synthesis) | Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course | Optimal care protocols for standard patient care and prevention of complications",France,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Policies for public health, disease control & community resilience","Pathogen morphology, shedding & natural history | Disease pathogenesis | Supportive care, processes of care and management | Clinical trial (unspecified trial phase) | Communication",2022 +P23595,101075007,Clinical Trial Competitive multinational assessment timelines in the European Union ensuring Regulatory Excellence,"Therapeutics continue to play a critical role in the response to the COVID-19 pandemic. They help to save lives, speed up recovery time and help to avoid or reduce periods of hospitalisation. However, joint efforts are still needed to ensure access to safe and effective therapeutics. The EU Strategy on COVID-19 therapeutics highlighted that robust clinical trials are an essential source of evidence for the authorisation of innovative COVID-19 medicines and there is a need for speeding up and coordinating their authorisation. This joint action supports Member States to ensure expedited and coordinated assessments in a procedure conform to the Clinical Trial Regulation (EU) 536/2014 but with timelines assuring expedited assessment and decision. This will allow for a fast authorisation of harmonised clinical trial protocols for COVID-19 therapeutics in the Union and will make the Union more attractive to run large, multi-country trials The joint action is expected to result in an increase in the number of coordinated assessments of COVID-19 therapeutics'Äô clinical trials and on a reduction of the time needed to authorise such trials.",,2024,FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS,2259995.48,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies | Therapeutic trial design,2022 +P23596,101016203,"Boosting Innovation for COVID-19 Diagnostic, Prevention and Surveillance.","The novel corona virus causing COVID-19 overwhelmed Europe and the world in just a few weeks'Äô time. Small and Medium-sized Entrerprises (SMEs are put at very high risk by the slowdown or shutdown of economic life in their countries 'Äì exactly those companies who ensure the development of innovative solutions urgently required for counteracting the impacts of COVID-19 and for helping to control possible future outbreaks alike. In view of this situation, accelerated uptake of innovative technologies to tackle COVID-19 is most needed. In order to give an efficient and fast answer to this challenging situation, we propose building an Innovation Hub for the addressed technologies: an innovative open access platform to offer companies and reference laboratories the capabilities, expertise, networks and services required for the assessment, development, prototyping, testing, scaling-up, pilot production and market exploitation of innovative technologies to tackle COVID-19 pandemic. This approach will be based in the Open Innovation Test Beds (OITBs) concept, to incorporate lessons learned from those Innovation Actions, reducing time for putting in place such HUB and ensuring its successful implementation for a swift impact to the current situation. Our approach will include leading applied research and innovation centers in Europe, together with entities specialized in building OITBs, and reference clinical sites. INNO4COV19 will provide funding to third parties to help them achieve the desired objectives. Presence of leading applied research EU institutions in the Consortium will help to obtain a huge impact and to find and attract innovators across Europe to offer new solutions for COVID-19 pandemic and other potential future outbreaks. Europe needs to reinforce its technological leadership and rebuild an industrial sector capable to protect our citizen'Äôs safety and well-being, and INNO4COV-19 will help in catalyzing the change.",,2022,INTERNATIONAL IBERIAN NANOTECHNOLOGY LABORATORY,7302564.52,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Portugal,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P23597,101016087,PORTABLE PLATFORM FOR THE ASSESSMENT OF MICROVASCULAR HEALTH IN COVID-19 PATIENTS AT THE INTENSIVE CARE,"As COVID-19 spreads worldwide, the surge in patients requiring intensive care unit (ICU) admission has been overwhelming to the healthcare systems. Critical care triage to allow the rationing of scarce ICU resources is needed but is hindered due to lack of personalization. The management of acute respiratory failure and hemodynamics is critical at the ICU. In fact, of the seven million COVID-19 cases (end of May 2020) 3-12% required mechanical ventilation which forms the primary target of VASCOVID where we focus on; (1) patient stratification derived from endothelial function evaluation, and, (2) evaluation of cardiopulmonary interactions that personalizes conservative ventilation strategies in order to avoid ventilator-induced lung injury and readiness to wean from the ventilator. VASCOVID will deploy and mature our portable, non-invasive and real-time health monitoring platform for this purpose. This platform combines two bio-photonics technologies, time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy, and is the fruit of long-term collaboration between core project partners in two European projects (BabyLux and LUCA) where high technology readiness level have been achieved for neuro-monitoring and thyroid cancer screening. VASCOVID will adapt the platform to meet the needs of a typical ICU dealing with COVID-19 and other patients requiring ventilation, as well as to leverage large-scale testing of new treatment procedures and therapies aimed to address microvascular impairment and to reduce extubation failure on ICU patients weaning out of mechanical ventilation life-support. The platform is easy to deploy, cost-effective and provides real-time fast results and its transition to clinical practice will be eased through this project by pushing CE certification. Our inter-disciplinary consortium is well-suited for these activities and will interact closely with our on-going clinical study spanning four countries and a dozen hospitals.",,2023,FUNDACIO INSTITUT DE CIENCIES FOTONIQUES,2449617.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23598,101016131,AI-based chest CT analysis enabling rapid COVID diagnosis and prognosis,"This icovid project is the continuation of the pro bono icovid initiative that developed the CE-marked and FDA permitted AI-based CT analysis software, icolung, and made it available in over 65 hospitals worldwide. The icovid project aims to improve the software making it of greater value as the clinical needs evolve, validating it in renowned academic centers and deploying it at large-scale across Europe. icolung is expected to have a significant societal impact by increasing confidence when making a CT diagnosis and providing accurate quantification of disease and prognostic information in patients with suspected COVID-19 disease. Importantly, even in a low prevalence setting icolung may have a much higher sensitivity and a comparable specificity for the diagnosis compared to the RT-PCR testing used currently. Identifying infected patients earlier will reduce the risk of further contamination and allows the right patient management to start earlier. icolung also predicts the risk of developing severe COVID-19 disease for which ICU admission and mechanical ventilation are required, allowing optimization of patient care. This project will significantly strengthen the position of two European SMEs in the rapidly growing market of AI in healthcare. One of them is coordinating the project and the consortium involved, enabling quick responses in a rapidly changing environment. The consortium builds further on existing organic collaboration and contains world-renowned experts of which multiple are part of the Executive Committee of the European Society of Thoracic Imaging.",,2023,ICOMETRIX NV,3807228,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23602,101046109,European Clinical Research Alliance on Infectious Diseases - PRIMary care adaptive platform trial for pandemics and Epidemics,"European citizens affected by COVID-19 have been well-served by landmark clinical trials in hospitals that have found treatments that save many lives. However, there are fewer opportunities for people in the community to contribute to the urgent mission of finding treatments that speed recovery, and reduce the need for hospital admission in the first place. Desperately needed, evidence-based therapeutics for use in primary care have the potential for considerable reach and impact on individual suffering and functioning, as well as on the sustainability of health services. ECRAID-PRIME, a European Adaptive Platform Trial (APT) of COVID-19 therapeutics in primary care will build on many years of EU investment in infrastructure for primary care trials and a mature primary care research network that has pioneered novel, efficient, platform clinical trial designs. ECRAID-PRIME, with a focus on early phase studies of safety and efficacy of exciting candidate treatments for COVID-19 will be rapidly set up. Its goal is to test at least four strong candidate treatments, identifying suitability for inclusion in the next phases of research, and so leading to critical additions to the primary care therapeutic armamentarium against COVID-19. ECRAID-PRIME'Äôs primary care focus will help complete the vison for a lasting, integrated, comprehensive and sustainable European clinical research preparedness and response capacity, ECRAID, that will provide a full, integrated suite of international priority clinical trials in intensive care units, hospital wards, and now in primary care.",,2024,UNIVERSITAIR MEDISCH CENTRUM UTRECHT,11298325.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Phase 0 clinical trial | Phase 1 clinical trial",2021 +P23603,101137196,Preventing non-communicable diseases caused by the post-acute phase of cOvid-19 INfecTion,"The post-acute phase (PAP) of COVID-19, occurring 'â•4 months after the acute phase, is associated with an increased risk for the development of non-communicable diseases (NCDs). The risk of complications in this phase does not depend on the severity of the acute phase. In the EU, more than 183 million cases of COVID-19 have been reported and up to 70% of patients suffer reduced organ function in the PAP. Our conservative estimate it that 5% of people who have suffered COVID-19 are at risk of developing NCDs of the pulmonary, cardiovascular and renal systems due to the PAP. To avoid the significant socioeconomic costs related to this burden, POINT will develop knowledge-based biomarkers for prevention and management of NCDs, a virtual twin model that offers clinical decision support, and clinical guidelines and recommendations for the entire health care value chain with special attention to vulnerable groups. We will fulfil an unmet need for knowledge and tools to minimize the risk factors of the PAP at the optimal point in time, when healthcare systems will have to redirect their focus from the acute phase of COVID-19 to the post-acute phase. The outcomes of POINT will aid the health care value chain already from an early phase of the project. Furthermore, POINT will correlate and promote knowledge on the development of NCDs in general and the risks of PAP from other infectious diseases. POINT will meet the challenges with a holistic approach from a truly interdisciplinary consortium consisting of clinical experts, molecular biologists, behavioural scientists, and computer scientists, who will take advantage of cohorts of more than 6 million Europeans, and cross-sectional biobanks from more than 6000 Europeans. Researchers will work together with standardisation experts, an end-user organization representing >120.000 physicians, as well as a dedicated partner for data management ensuring rapid absorption of the outcomes of the project by all stakeholders.",,2027,KOBENHAVNS UNIVERSITET,14688278,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2024 +P23604,961108,Novel COVID-19 POC Screening Tool Based on Proprietary Nano-Sensors and ML Techniques,"The NanoScent core technology is based on proprietary and patent-protected nano sensors coupled with machine learning algorithms. At the heart of the solution is the ability of sensing and recognizing scents. Combining novel chemical nano sensors with advanced machine learning techniques, NanoScent technology tackles the challenging tasks of VOCs detection faced by the industry, organizations, authorities and individuals. NanoScent scent recognition system consists of low-cost, easy-to-use, fast-responding, high-sensitive Chemiresistor Sensors; Scent Recorder; and Scent Recognition Software. There is no effective method for early stage screening COVID-19, for the purpose of effective virus spread prevention. For example, gold standard -PCR method has 'Ǩ100s cost, intended for use by professionals at qualified laboratories, and has 1-2 days result delivery time, in contrast real-time and low-cost thermometer method has very low sensitivity and specificity, meaning that many people infected in COVID-19 may not be identified on time and immediately be isolated from healthy people. We truly believe that our technology could serve to help in the global effort of effective prevention of the spread of viruses. We are already commercializing our application for different industries. The COVID-19 and a long list of potential clients contacting us for a solution made us prioritize the detection of COVID-19. Founded in 2017 by two experienced entrepreneurs and industry experts, NanoScent Ltd. is developing a scent recognition technology for the aims of people safety, personal wellbeing, environmental protection and energy efficiency. NanoScent offers a system to visualize scent 'Äì scientifically referred to as a mixture of volatile organic compounds (VOCs), in order to let industry, organizations, authorities and individuals make better decisions based on a new set of 'Äòeyes'Äô on everyday processes with an aim to protect the community from dangerous compounds.",,2022,NANOSCENT LTD,2949096.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Israel,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23605,961844,Optimal use of hospital resources and intervention using suPAR for improving prognosis and care for patients with COVID-19,"Optimal use of hospital resources and intervention using suPAR for improving prognosis and care for patients with COVID-19 To optimize hospital resources, it is necessary to test which patients that can be sent home (mild outcome of infection) and which patients that should be admitted to hospital (high risk patients). This will deliver on the tasks: 1) Identify patients that can safely cope with the infection at home and 2) Identify high risk patients early in the disease and 3) Select high-risk patients that may benefit of therapy. But how can we identify low- or high-risk patients? The suPARnostic test developed by ViroGates and CE/IVD approved for clinical use is highly prognostic marker for 30-day mortality. Some hospitals have suPAR in routine clinical assessment of patient risk, and preliminary data support that suPAR levels can triage whether patients with COVID-19 will have a mild or a severe outcome of COVID-19 and thereby select which patients that could be discharged or admitted. We aim to transfer manufacturing, upscale and implement the suPARnostic technology across hospitals in Europe to improve the risk stratification of COVID-19 patients and optimize hospital resources. We furthermore provide a test method that can identify high-risk patients that may benefit from experimental therapeutic interventions that may impact on outcome. The identification of patients in high risk of mortality (patients with high suPAR) provide a possibility to intervene.",,2022,VIROGATES AS,1044288.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Denmark,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P23606,962678,COVID-19 Telemedicine 'Äì an infectious disease management tool for governments all over Europe that will reduce casualties from COVID-19 as well as prepare governments for the next wave of epidemics.,"COVID-19 telemedicine will provide the solution for remote monitoring and telemedicine for COVID-19 patients. The platform is developed for COPD and heart patients over the past 6 years and with this project we will be able to innovate home-monitoring, scale it up massively and collect big data to analyse the development and patterns through AI. The result will be a fully rolled-out infectious disease management tool for governments all over Europe that will reduce casualties from COVID-19 as well as prepare governments for the next wave of epidemics. The company is formed to meet the need for a solution for the COVID-19 outbreak. This innovation forms the foundation of the company and the team is put together because they are the right people to execute the vision of actually making a major impact against the novel corona virus. They are experts in scaleup, product development, fundraising, marketing and communication. The support and interest in the solution is massive even at this TRL 8 stage of the first two parts of the full innovation that is threesome. This innovation project will elevate the solution to save lives!",,2022,Levvel Health ApS,2872684.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Denmark,,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions",2020 +P23607,101016216,Unravelling Data for Rapid Evidence-Based Response to COVID-19,"unCoVer is a functional network of research institutions collecting data derived from the provision of care to COVID-19 patients by health systems across Europe and internationally. These real-world data allow for studies into patient'Äôs characteristics, risk factors, safety and effectiveness of treatments and potential strategies against COVID-19 in real settings, and complement findings from efficacy/safety clinical trials where vulnerable groups, and patients with comorbidities are often excluded. The network will facilitate access to otherwise scattered datasets, and build computational and analytical platforms to streamline studies on risk characterisation, and prediction modelling using standardised pooled data derived from real life practices. It will fill data gaps, unify current initiatives and create downstream exploitation opportunities for researchers and public health strategies to optimise COVID-19 strategies and minimise the impacts of future outbreaks",,2023,INSTITUUT VOOR TROPISCHE GENEESKUNDE,3536979.2,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Belgium,,,,2020 +P23608,961916,Rapid and easy- test for Coronavirus infections,"The coronavirus outbreak in 2019 (Cov-19) has challenged the global healthcare system to contain a virus with unprecedented contagious capabilities. A major aspect for controlling the Coronavirus pandemic is the implementation of tools that allow rapid screening of patients at the healthcare centers and not only. Fast and accurate diagnosis of early infections will facilitate the clinical management of the virus, and will improve patients' prognosis. The diagnostic gold standard for Coronavirus is the RNA detection of pharyngeal swab specimen by RT-PCR. However, the limitations of time, need of devices and specialized personnel to perform RT-PCR, combined with the rapid spread and universal susceptibility to the general population, make this diagnostic technique incompatible with the urgent medical needs. Moreover, the number of RT PCR kits available are limited and the production cannot cope with the high demand. The main objective of this study is to develop a rapid, easy and economical screening test for Coronavirus with the capability to achieve results in less than one hour, with high sensitivity and specificity. The test will be used to screen asymptomatic or mildly symptomatic individuals, which can risk community transmission to population categories at a higher risk (elderly with underlying conditions, among others). Corona-Test is a lateral flow strip test similar to the well-known pregnancy test. Herein, we are aiming to validate the diagnostic accuracy and screening efficacy of Corona-Test. This strategy could provide the means to prevent and control the disease. The objective of this project will be to bring the test to market within 12 months.",,2022,SOMAPROBES SL,1699082,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23609,101103241,Practical strengthening of regulatory and ethics oversight on clinical trials in West Africa using Lassa Fever vaccine development projects and increase regulatory maturity level in targeted countries,"The proposed strengthening project for clinical research oversight in ECOWAS region, consists of practical training of regulatory and ethics experts by exposing them to Lassa Fever vaccine development from early to late clinical stage. The exposure to novel technologies in vaccine development and the opportunities to responsibly oversee the full clinical development pathway of vaccines for Africa can inspire and attract regulators and ethics experts/talents, and by this contribute to maintaining, enhancing and further developing the workforce at the agencies and ethics institutions. The project intends to enhance the Maturity Level for Regulatory Systems and clinical trial oversight function of 2-4 authorities in the ECOWAS region. Ghana FDA will lead the intended work, with CEPI as project coordinator and WAHO ensuring the dissemination and engagement among ECOWAS countries. The consortium between GFDA, WAHO and CEPI is confident to assure high quality regulatory and ethics oversight during Lassa Fever vaccine development and to create preparedness of ECOWAS NRAs not only for Lassa vaccine future licensure but also for decisions related to emergency use in case of a major Lassa Fever outbreak. Using the AVAREF platform for scientific advice and CTA simulations and including ECOWAS observer countries in real live clinical trial application assessments will strengthen the common advice and review processes and lead to reliably generate fast decisions by NRAs and ECs in a seamlessly coordinated way. When processes from application to decision are reliable and fast, developers will prefer using AVAREF platform even for single country clinical trial applications. This will open further possibilities for coordinated involvement of observer countries for training purposes. Seamlessly coordinated collaboration on the basis of harmonized and well-defined processes between NRAs, NECs and AVAREF will promote clinical research in Africa and help the AMA operationalization.",,2025,COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS,551008.27,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Arenaviridae,,,,,,,,,Lassa fever,European Commission,Europe,Europe,Europe,Unspecified,,,,Norway,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Research | Policy research and interventions,2023 +P23610,101135094,Zoonoses Emergence across Degraded and Restored Forest Ecosystems,"Ecosystem degradation and biodiversity loss may facilitate the emergence of zoonotic diseases. The 4-year ZOE project will analyze the links between landcover and land use changes in tropical biodiversity hot-spots facing loss of primary forest and biodiversity and in temperate regions that have undergone ecosystem degradation and deforestation over historical timescales. In areas experiencing different levels of ecosystem degradation, biodiversity assessments will be based on remote sensing-based GIS analysis of landscape structures, geobotanic plant mapping, and targeted trapping of rodents, ticks, and mosquitoes, as prototypic reservoirs and vectors of zoonotic diseases (macro-organism scale). Host- and soil-associated microbiome and virome high-throughput sequencing will be combined with assessment of human exposure to prototypic zoonotic pathogens, using high-throughput serological analyses (microbiological scale). ZOE will link with local communities and stakeholders to address perceived land use and land cover changes, disease occurrence, coping strategies, and risk behaviour. Results will be synthesized in modelling and risk mapping frameworks linking biodiversity loss and zoonotic disease risks and tested in forecasting scenarios to feed into cost-efficient monitoring schemes and early warning systems. An online knowledge platform will be created to link all relevant stakeholders of the biodiversity-health nexus, including other EU-funded consortia, national and supranational organizations stakeholders, local communities, and the public. A joint stakeholder conference will be organized, and community engagement workshops will specifically co-create and advance knowledge in local communities involved in ZOE. The ZOE project is proposed by an interdisciplinary consortium with expertise in geography, geobotanics, ecology, virology, immunology, epidemiology, sociology, psychology, anthropology and science dissemination from 7 EU and 4 American countries.",,2027,CHARITE - UNIVERSITAETSMEDIZIN BERLIN,4399432.4,Animals | Human Populations | Viruses | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Other,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Vector biology | Disease surveillance & mapping | Approaches to public health interventions | Community engagement,2024 +P23611,101003480,"COVID-19-Outbreak Response combining E-health, Serolomics, Modelling, Artificial Intelligence and Implementation Research","Among the biggest challenges in the COVID-19 outbreak are the lack of triangulation of clinical, epidemiologic and immunological information for evidence- based response strategies. Our overriding ambition is to overcome this deficit through field studies and implementation research in specific populations early enough to already serve in the response to the current outbreak. Four technical work packages (WP) address the four main objectives: To provide real-time clinical data to improve risk assessment and response, deploying an established mHealth Surveillance Outbreak Response Management and Analysis System (SORMAS) in Nepal, Ivory Coast, Ghana and Nigeria; countries likely to be affected more intensively than the EU.(WP I) To implement differential serolomics (multiplex serology) for population serum samples from Germany and Nepal for investigating pre-existing cross or partial immunity against COVID-19 and impact on susceptibility.(WP II) To apply comprehensive modeling, sampling and artificial intelligence on data from the first two work packages in order to assess predictors for severe outcome, transmission dynamics and intervention effectiveness.(WP III) To measure and improve quality of epidemic containment measures through implementation research in countries particularly vulnerable to the COVID-19 epidemic, in order to tailor effective and efficient control measures to health systems realities in Nepal and Ivory Coast, and to reduce the intensity of importation into the EU. (WP IV) We combine a) an accelerated ad-hoc outbreak response to address the urgency and b) a sustainable strategy to serve beyond the current public health threat from COVID-19. Software maturity, established networks, pre-approval investments and interdisciplinary expertise among partners - including first hand from China - shall generate first findings within weeks, such as validated criteria for high-risk groups, effectiveness of contact tracing, set-up serolomics platform.",,2023,HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH,3007522.55,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health | Innovation,,,Germany,,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Supportive care, processes of care and management | Approaches to public health interventions",2020 +P23612,101016046,Telehealth-ready AI-powered multi-parametric system for surveillance of COVID-19 and cardio-pulmonary chronic patients,"The COVID-19 outbreak causes world health care systems to crumble under the load. This consortium proposes a Home-use/Point-of-Care device, incorporating improved clinical parameters, providing early detection, and monitoring of COVID-19 patients. This consortium presents a computerized auscultation device 'Äì the PyXy 'Äì which provides expert-level lung and heart check-up. The PyXy brings breakthrough capabilities in terms of sound and infrasound analysis, body temperature, blood oxygen levels, heart rate and respiratory cycle, all analyzed by artificial intelligence (AI) for accurate diagnostic data. The device recently showed very promising results in relation to managing COVID-19 disease. Using H2020 funds, the consortium plans to introduce the PyXy to the market within 22 months: allowing anyone to perform diagnostic at an accuracy not normally accessible to the medical staff. In this project the consortium will collect COVID-19 patient data and take the PyXy to high volume manufacturing level. The consortium gathers two technology provider SMEs 'Äì Sanolla, the developer of the PyXy device, and Medsensio, experts in AI for classification 'Äì together with an established player in the medical devices and e-health solutions 'Äì Riester. The work will be done in collaboration with four healthcare service providers (Natali, BeneVit, Helgeland and PhilonMed) to ensure the PyXy will be accepted by the market from all possible aspects. We believe that PyXy is capable to substantially reduce the health-economic impact on healthcare and elderly care services by preventing hospitalization in emergent-care situations. In addition, as PyXy can be used by lesser skilled individuals, we believe it will potentially bridge the gap in care settings that face extreme shortage of skilled workers, and can even be used by informal caregivers at home reducing the overall hospitalization rate even further.",,2023,SANOLLA LTD,5835930,Human Populations | Other,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Israel,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23613,101016000,Cyber-Physical Intensive Care Medical System for Covid-19,"The European health services have well responded to the Covid-19 emerging crisis, especially if and where the intensive care unit (ICU) capacities were sufficient, were prepared and collectively cooperating, sharing knowledge and were able to protect from further spreading of the disease among the healthcare workforce and the patients. Today, only 47% of hospitals have the recommended coverage of intensive care specialists and they are unevenly distributed between centres and periphery. The Cyber-Physical System for Telemedicine and Intensive Care (CPS4TIC) enables existing or new ICU structures to transform and operate as one ICU Hub with one central ICU and connected ICUs in peripheral hospitals. CPS4TIC was used successfully in the first wave of Covid-19 to ensure efficient and effective diagnosis and treatment of Covid-19 patients, while reducing the risk of infection drastically. The CPS4TIC consists of a telemedicine cockpit, telemedicine consoles at each peripheral hospital, a connector platform and smart bedside hubs including robotic arm at the bedsides of both, the central telemonitoring clinics and the peripheral telemonitored hospitals. The ICU hub operates telemedicine, continuous real-time telemonitoring and bedside smart care environment. The bedside smart care environment reduces the risk of infection for the health workforce significantly both for the central and the peripheral hospitals. ICU4Covid will deploy and test the CPS4TIC at large-scale, in 4+4 ICU Hubs in Europe (4 from initial consortium and 4 selected by an Open Call), involving more than 30000 patients/year with a coverage of approximately 60 Million citizens.",,2022,UNINOVA-INSTITUTO DE DESENVOLVIMENTO DE NOVAS TECNOLOGIAS-ASSOCIACAO,12911435.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Portugal,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P23614,101066146,Molecular mechanisms underlying Zika virus transmission by Aedes aegypti mosquitoes,"The public health response to emerging mosquito-borne viral diseases is often inefficient, because the causative agents are recognized and the prevention measures are deployed, only after the disease has spread. To predict which viruses and mosquitoes have the highest potential to cause future outbreaks, understanding the mechanisms determining the virus susceptibility of mosquitoes and the mosquito transmissibility of viruses is needed. In this study, I propose a two-pronged approach to identify both the viral and mosquito factors involved in molecular compatibility between the human pathogenic Zika virus and its main vector Aedes aegypti by combining my skills in molecular virology with the host lab'Äôs expertise in mosquito experimental infections in vivo. First, I will examine the mosquito-virus protein interactome by a proteomics strategy based on cross-linking, immunoaffinity purification and mass spectrometry. Mosquito factors regulating virus susceptibility will be identified by subtractive comparison of virus-binding mosquito proteins between two mosquito strains displaying different levels of Zika virus susceptibility. The correlation between virus susceptibility and the identified proteins will be validated by gene-knockdown assays and expression surveys using a collection of mosquito strains. Second, I will use an innovative reverse genetics system to create chimeric Zika viruses from two parental virus strains with different levels of mosquito transmissibility. The viral genes required for efficient transmission by mosquitoes will be identified by comparing transmissibility between chimeric constructs. Together, this project will provide important new insights into vector-virus specificity and significantly improve our understanding of mosquito-borne virus emergence.",,2025,INSTITUT PASTEUR,211588.2,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Vector biology",2023 +P23615,101134969,Restoring Ecosystems to Stop the Threat Of Re - Emerging Infectious Disease,"Restoring Ecosystems to Stop the Threat Of (Re-)Emerging Infectious Diseases: There is a growing body of evidence that landscape degradation is linked to zoonotic spillover risk. Large scale restoration is increasingly being touted as an effective solution for mitigating against a range of anthropogenic impacts and is also hypothesised to protect against zoonotic disease spillover. However, little is known about the mechanisms with which restoration may provide this protection. It is commonly assumed that restoration mirrors in reverse the processes that occur during degradation; however, it is likely that this relationship is in fact asymmetric. Rarely can restored landscapes be returned to a state similar to that of pristine ecosystems, and often restored landscapes need to fulfil a range of environmental and socioeconomic requirements that inherently prevent them from doing so. Additionally, the spatiotemporal scale necessary to effect positive change is context dependent, and the type of restoration necessary to protect against zoonotic spillover is currently unknown. Ecosystem restoration can vary widely in type, scale and context and can also change how humans interact with their environment, which may have unexpected consequences for zoonotic disease spillover. Given the complexity of these interactions and their effect on disease, it is vital that we understand how restoration specifically might impact wildlife disease and emergent spillover risk.",,2027,UNIVERSITEIT ANTWERPEN,4304523.3,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Environmental stability of pathogen | Animal source and routes of transmission,2024 +P23616,101060825,Rebuilding governance and resilience out of the pandemic,"Culminating more than a decade of crisis in Europe, the Covid-19 pandemic has opened an unprecedented window of opportunity for institutional and policy change, not only at the 'Äúreactive'Äù level of emergency responses, but also to tackle more broadly the many socio-political challenges caused or exacerbated by Covid-19. Building on this premise, REGROUP (Rebuilding governance and resilience out of the pandemic) aims to: 1) provide the European Union with a body of actionable advice on how to rebuild post-pandemic governance and public policies in an effective and democratic way; anchored to 2) a map of the socio-political dynamics and consequences of Covid-19; and 3) an empirically-informed normative evaluation of the pandemic. REGROUP pursues this threefold objective via a multi-level (national, supranational, international) and multi-sphere (political, societal, ideational, digital) research approach, and guided by three overarching analytical themes: 'Äúreordering'Äù; 'Äúrisk'Äù; 'Äúresilience'Äù. We operate in nine collaborative work packages'Äîgrouped in three blocks: 'Äúdiagnosis'Äù, 'Äúevaluation'Äù, and 'Äúprescription'Äù'Äîbringing together expertise and methods from a range of social sciences and humanities. Doing so, we advance the state of the art conceptually, theoretically, and methodologically. REGROUP is conducted by a consortium of 13 internationally renowned institutions, committed to scholarly excellence, inclusiveness, and open science. The project is designed to achieve a high degree of policy, societal, and scientific impact, which it will achieve via a multi-pronged dissemination and communication strategy. This includes links to some of the EU'Äôs main debates and events, such as the Health Union, the Green Deal, the Digital Decade, the Economic Governance Review, the Conference on the Future of Europe, and the 2024 European Parliament elections.",,2025,RIJKSUNIVERSITEIT GRONINGEN,2999997,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts,2022 +P23618,961522,AI software for the automated detection of covid-19 infection on chest CT,"An AI platform to support medical practitioners to screen potential COVID-19 patients using medical imaging. Aidence is creating a new product to automatically analyse chest CT scans and diagnose the presence of corona (covid-19) viral infection. The product receives an image from the CT scanner, analyses it, and returns an easy-to-read report on the most likely diagnosis. This is done in the background fully automatically and the report is available for medical staff within a few minutes. Studies indicate CT is as least as sensitive as the current RT-PCR kit for testing, and is very fast. It is useful in case no kits are available, or when they are inconclusive, and/or radiology staff is unavailable or untrained. This product can be used for triaging as well as longer-term monitoring and early warning for future outbreaks. Because the solution will be operating on all CT chest scans and fully automated, once deployed in hospitals around Europe it will also serve as a case registry for management reporting and tracking of a new potential corona outbreak.",,2021,AIDENCE HOLDING BV,2082036.25,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23619,961787,Harmless Respiration for Intensive Care Patients decreasing mortality and shortening stays 'Äì including COVID-19 patients,"The current outbreak of COVID-19 is incisively pointing towards the importance of optimal mechanical ventilation in Intensive Care. Improved mechanical ventilation saves lives. Last year, we have seen multiple cases in which our mechanical ventilator suited only for the Operating Room (OR), was used off-label in ICU to ventilate severely lung-ill patients. Doctors claim patients would have died if our device would not have been used. These case reports are supported by more fundamental evidence published in March 2020: in-vivo studies on pigs having similar lung-illness as with the current COVID-19 outbreak (called Acute Respiratory Distress Syndrome) have shown superior result with our disruptive ventilation method, called FCV¬Æ. Half of all patients on higher grade Intensive Care Units need mechanical ventilation. However, current ventilation methods are known to damage the lungs in these vulnerable patients. This significantly prolongs ICU stay and increases mortality. The damages relate to the passive expiratory phase during mechanical respiration, which is fast and uncontrolled resulting in shear stress and collapse of the distal lung parts. Prolonged ventilation then initiates inflammatory responses in the lungs. We have developed a new ventilation method controlling the expiration, preventing lung damage. In 2017 our innovative OR ventilator (Evone) was brought to the market. Having performed over 1,000 OR patient cases and 5 small clinical studies till date, clear superior ventilation and improved lung mechanics has been shown. However, the largest unmet medical need related to ventilation is on ICU. The objective of this proposal is to bring this superior ventilation technology to ICUs in Europe, the Middle East and in 2nd phase the USA and by that, lower ICU mortality by 20% and ICU stay with 15%. This means 44,800 lives to be saved in European ICUs, each year (valued at 'Ǩ 90 billion) and a reduction of 'Ǩ2 billion in annual European healthcare costs.",,2022,VENTINOVA MEDICAL BV,2948277.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P23620,101016127,Improving the Preparedness of Health Systems to Reduce Mental Health and Psychosocial Concerns resulting from the COVID-19 Pandemic,"The mission of RESPOND is 1) to identify critical resilience factors and specific vulnerable groups at risk of immediate and long-term adverse mental health impact of the COVID-19 pandemic; 2) To improve the resilience, wellbeing and mental health of frontline health and care workers and other vulnerable groups by implementing scalable World Health Organization (WHO) programmes, and 3) to steer future policy decisions by understanding and disentangling the effects of the COVID-19 pandemic and different public health containment and subsequently relaxation strategies on mental health and wellbeing in vulnerable groups across Europe'Äôs different health systems. RESPOND is centred around core questions regarding the short and long-term impacts of the pandemic on mental health and health inequalities on vulnerable groups within the general population, including frontline workers. In the first immediate delivery phase, an impressive set of existing longitudinal datasets are examined for resilience factors and risk factors. Furthermore, the responsiveness of health systems and identification of best practice responses that protect resilience, mental health and wellbeing are assessed in eight EU countries. The long-terms effects are determined of the pandemic and the control measures on demand for (mental) health services in health registers in Sweden, Lombardy and Barcelona and the scalable WHO SH+/PM+ stepped care programmes adapted for COVID-19 will be implemented and evaluated both in frontline workers and vulnerable groups. RESPOND provides policy recommendations within 3 months on vulnerability factors for developing poor mental health resulting from current containment and mitigation measures. Further lessons learnt and evidence-based policy recommendations will be made available during the project'Äôs lifetime through Policy Briefs in month 6, 12, 18, 24 and 36 for immediate consideration and use by all EU member states.",,2024,STICHTING VU,7406433.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Health Personnel | Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2020 +P23621,101015736,European Research and Preparedness Network for Pandemics and Emerging Infectious Diseases,"The overall objective of this 5-year project is to build a multinational, adaptive European COVID-19 and emerging infectious diseases trial network, based on existing initiatives, experience and expertise, allowing European expansion of DisCoVeRy (WP1) and the establishment of a COVID19 adaptive platform trial (WP2). The DisCoVeRy trial, designed as a multi-arm adaptive repurposing trial, initiated in France, has the potential to expand to many other European countries with appropriate support in terms of multinational funding and trial management capacity. This will complete the evaluation of repurposed drugs, while building a European clinical trial network which, together with other European networks such as the Solidarity trial, will design and run a new European platform trial. EU-RESPONSE will swiftly generate robust evidence for drug repurposing or registration, through a modular trial framework allowing most European hospitals to participate at their preferred level of commitment, thus building a network of investigation sites within European and associated countries. Cooperation with other European platforms, in particular the RECOVER consortium platform will be achieved through a joint coordination mechanism aligned with European and national policies (WP3), ensuring a coordinated strategy for the European COVID-19 Adaptive Platform Trials, their complementarity in providing access for requests for a new domain or arm, their synergy and cross-fertilization through the development of a common toolbox for the development and the management of Adaptive Platform Trials. Joining forces in Europe and with international partners, it will contribute to the global clinical trial capacity for urgently meeting the expectations of society and developers. It will also boost multinational cooperation in Europe and promote the establishment of adaptive platform trials in other diseases, and will have a major impact on epidemic control.",,2025,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,17605784,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Therapeutics research, development and implementation",Prophylactic use of treatments | Therapeutic trial design,2020 +P23622,101015924,"Non-intended health, economic and social effects of the COVID-19 epidemic control decisions: Lessons from SHARE (SHARE-COVID19)","The non-intended consequences of the epidemic control decisions to contain the COVID-19 pandemic are huge and affect the well-being of European citizens in terms of economics, social relationships and health: Europe is experiencing the largest recession since WWII; social contacts have been interrupted; people avoid seeking medical treatment in fear of infection. The overarching objective of this project is to understand these non-intended consequences and to devise improved health, economic and social policies. In our policy recommendations, we strive to make healthcare systems and societies in the EU more resilient to pandemics in terms of prevention, protection and treatment of the population 50+, a most vulnerable part of the population. The project aims to identify healthcare inequalities before, during and after the pandemic; to understand the lockdown effects on health and health behaviours; to analyse labour market implications of the lockdown; to assess the impacts of pandemic and lockdown on income and wealth inequality; to mitigate the effects of epidemic control decisions on social relationships; to optimise future epidemic control measures by taking the geographical patterns of the disease and their relationship with social patterns into account; and to better manage housing and living arrangements choices between independence, co-residence or institutionalisation. The project pursues a transdisciplinary and internationally comparative approach by exploiting the data sources of the SHARE research infrastructure. It covers all EU MS. The project'Äôs team represents medicine, public health, economics and sociology and has worked together since the creation of SHARE. It is experienced in translating data analysis into concrete policy advice. The project'Äôs policy recommendation are targeted at policy makers in the Commission and in national ministries as well as at national and international NGOs and social organisations.",,2024,MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV,8011785.6,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P23623,101005122,"rapiD and secuRe AI imaging based diaGnosis, stratification, fOllow-up, and preparedness for coronavirus paNdemics.","In this project, a multinational consortium of high-tech SMEs, academic research institutes, biotech and pharma partners, affiliated patient-centred organisations and professional societies will achieve a multi-faceted diagnostic and prognostic platform and a precision medicine approach. This consortium will together realize a patient empowerment centred decision support system that will enable multiple stakeholders to participate in improved and more rapid diagnosis and prognosis, as well as the potential of precision medicine for accelerated development of new therapies. Citizens and patients will be empowered to contribute to the efficient planning and usage of resources. The project will begin by rapidly delivering a nomogram. Data from the Chinese epidemic will be used to validate and further optimise a European scalable radiological diagnosis/prognosis solution. Existing and new data and sample collection efforts will be used to perform molecular profiling, which - using advanced AI techniques will be shaped into a precision medicine approach. These initial outputs will undergo further enhancement and assessment to evaluate the value they add to the development of a decision support system. The entire effort will be supported by the deployment of a federated machine learning system that will allow for the GDPR compliant use of multinational data resources. The various iterations of the decision support system and the federated machine learning system will be made available to other coronavirus initiatives with the intent to develop a stakeholder community that forms the basis for a highly efficient innovation ecosystem. Our proposed study will be one of the first to develop innovative machine learning, and clinical procedure improvement that will potentially make a huge socio-economic impact for the coronavirus outbreak.",,2024,UNIVERSITEIT MAASTRICHT,13430724.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Epidemiological studies,Disease surveillance & mapping,2020 +P23624,101103204,The Integrate study : An adaptive platform trial for the development of a new intervention to combat Lassa fever in Africa,"Lassa fever (LF) is an acute febrile illness associated with bleeding, organ failure, and shock caused by Lassa virus. LF causes outbreaks in West African with in-hospital mortality up to 12%. Challenges in the clinical care of patients are multiple due to the limited availability of LF molecular diagnostics, the risk for nosocomial transmission, and the limited treatment options.There are currently no safe and effective treatment options available for LF, except ribavirin, the efficacy of which is debated. The clinical development and accessibility of effective treatment options would be a game-changer towards reducing mortality associated with this disease and limiting its socio-economic impact. Nigeria is the country by far most affected by LF in the world with about 80% of global cases. The INTEGRATE consortium builds on a more than 15 years lasting highly successful collaboration between leading European and West African institutions focusing on the joint priority to better understand, manage, and combat LF in West Africa. The overall objective of the INTEGRATE project is to establish a GCP-compliant adaptive clinical platform trial in West Africa (Nigeria and other countries) to test the efficacy, tolerability and safety of repurposed and novel drug candidates for the treatment of LF. To address this objective, we focus our activities on 3 specific objectives: - to develop and implement an adaptive randomised controlled phase II-III clinical platform trial evaluating drugs with proven preclinical activity against LF. - to build capacity for sustainable and independently conducted clinical research in West Africa by developing site, laboratory and medical care capacity through North-South and South-South technology transfer and training. This activity encompasses capacity building of the lead Nigerian institution in GCP compliant clinical trial sponsorship. - to engage communities with the proposed work plan and to assess acceptability of the trial.",,2028,UNIVERSITE DE BORDEAUX,8720000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III | Clinical Trial, Phase IV",Arenaviridae,,,,,,,,,Lassa fever,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial | Prophylactic use of treatments | Therapeutic trial design,2023 +P23626,101113427,Enhancing whole genome sequencing (WGS) capacities to respond to the COVID-19 pandemic and future health health threats in Estonia,"This project is a continuation of the past project 'ÄòEnhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the Covid-19 pandemic in Estonia'Äô and it aims to continue the work in the field of enhancing WGS and RT-PCR national infrastructures and capacities to respond to the COVID-19 pandemic and future health threats under the EU4Health Programme (EU4H). This project aims to finalize the WGS sequencing structure in Estonia Health Board as its mission is to improve health emergency preparedness and response to potential and existing health treats in the field of infectious diseases. In addition to sequencing capacity building also the improvement of laboratory information system (LIS) is proposed. The aim for new LIS is to be modern and flexible, based on micro services architecture and effectively adjustable. To improve the workflow, strengthen achieved capacities and offer more effective monitoring and enhanced preparedness in Estonia as well as in EU.",,2026,TERVISEAMET,1358201.04,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Estonia,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity | Health information systems,2023 +P23627,101107454,The Effect of Resistance to Epidemic Measures on Disease Spread and Mortality 'Äì What'Äôs the Role of Online Misinformation?,"Aim: The REMEDY project will provide innovative interdisciplinary empirical research that explores the driver and health consequences of resistant behaviour against epidemic measures, leveraging social science insights, economic and statistical methods and data science techniques. Background: In the advent of the COVID-19 pandemic, one pressing challenge for the public health response is the general resistance to legitimate public health policies driven by news media, influencers, extremist politicians, and rampant misinformation circulated on the internet 'Äì a potential information disorder due to an 'Äúinfodemic'Äù. There is, however, little understanding of the mechanism through which these potentially malicious messages propagate and how they, in turn, influence the behaviour of the population in opposing vaccine, mask-wearing, mobility restrictions, social distancing, and consequently leading to higher levels of morbidity and mortality. Methods: This project employs different quantitative and research methodologies to estimate the effects of behavioural resistance on the epidemic spread and excess mortality and whether online misinformation explains this resistance behaviour. First, we link real-world data on vaccine refusal, fines for non-compliance and the frequency and scale of anti-mask/vax/digital COVID-19 certificate protests to the local epidemic spread, hospitalisation and excess mortality rate over time. Second, after identifying the different types of online misinformation on COVID-19 and vaccines, we use geo-tagged digital records on search engines and social media to analyse the association between online sentiments towards public health measures and real-world resistance behaviour at a specific geographic unit. Impact: The project will not only provide hard evidence on the linkage between resistance behaviour and population health outcomes, but will also present the gravity of precariously allowing misinformation to flourish on the internet.",,2025,INSTITUT NATIONAL D'ETUDES DEMOGRAPHIQUES,228695.4,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,France,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy,2023 +P23628,101058697,Developmental immunotoxicity of perfluoroalkyl substances (PFASs) in a population of highly-exposed children,"Exposures to perfluoroalkyl substances (PFASs), a class of persistent chemicals, have been linked to an array of adverse health outcomes including reduced antibody response to vaccination. The COVID-19 pandemic has focused attention on the serious implications of PFAS immunotoxicity. However, there is a lack of epidemiological studies on clinical immune outcomes (e.g., infections or asthma) in children, whose developing immune system is highly sensitive to chemical exposures. This proposal (PFAS-ITOX) addresses this research gap by leveraging a unique cohort of children with a wide range of PFAS exposures (background to highly exposed) and detailed medical records to investigate the potential immunotoxic effects of prenatal and childhood PFAS exposures on clinically relevant outcomes, including COVID-19 incidence. It was discovered in 2013 that one of two municipal water supplies in Ronneby, Sweden was delivering water that was highly contaminated by PFASs from firefighting foam runoff at a nearby military airport. Earlier studies in Ronneby found that serum PFAS concentrations corresponded closely with residential address history, allowing residential history to be used as an accurate proxy for exposure. PFAS-ITOX uses this 'Äúnatural experiment'Äù to create a longitudinal cohort of children and evaluate whether high PFAS exposures are associated with clinical outcomes related to immunosuppression (e.g., counts of common childhood infections) and hypersensitivity (e.g., incidence of asthma). While existing studies of PFAS immunotoxicity rely on self-reported data or hospital admission records, I will use the Sk√•ne Healthcare Register, unique to southern Sweden, to identify outcomes at all levels of care, including primary care where many immune outcomes are diagnosed. The proposal's results will inform future PFAS research, provide necessary evidence for risk assessments, and provide critical information to health practitioners caring for highly-exposed individuals.",,2024,LUNDS UNIVERSITET,238318.96,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,Epidemiological studies,Disease susceptibility,2022 +P23630,101132545,European Vaccination Beyond Covid,"The project aims to build and validate implementation plans for Member States (MS) to equip them with operational and technical tools that enhance vaccination practices both in routine vaccination and in case of future outbreaks. Validation will be based upon innovative practices applied in the context of the COVID-19 pandemic. To achieve this objective, the project will retrieve evidence about vaccination practices from literature and implemented activities. These practices will then be mapped according to the public health goals they serve. A subset of reference practices will be identified for validating the implementation plans. Implementation plans will then be formalized, executed, and verified through pilot projects. Five tools have been selected upfront, belonging to five key dimensions: - Medical 'Äì Providing a vaccination decision support system to professionals and patients, - Social 'Äì Screening populations from existing databases for vaccination motivation. - Industrial 'Äì Using neutral packaging with an e-leaflet for flexible vaccine distribution, - Modelling and forecasting 'Äì Generating model-based evidence to predict the impact of interventions, - Digital 'Äì Delivering a portable European digital vaccination card, Each implementation plan defines: - a workplan to deliver necessary organizational, technical, legal, and ethical components of the tool, - when relevant, a specific plan to upgrade the operation mode during outbreaks. - the verification criteria to determine if implementation was effective, - budgetary elements to support the implementation decision. The tools resulting from pilot implementations will then be validated for their adequacy to the selected practices, their transferability and sustainability for MS, and the benefits that would result from their implementation. Finally, the implementation plans, their verification and validation outcomes, and related promotional material will be delivered to MS for further uptake",,2026,PANEPISTIMIO KRITIS,7093796.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Greece,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Other secondary impacts,2023 +P23632,101130866,"Contested Conditions in the Wake of Covid-19: Relations between Autobiography, Media, and Illness","Autobiographical narratives about contested conditions have been published in Western media, which often highlight personal experiences of dismissal in health care and public. Scholarship in medical humanities argues that illness narratives can give voice to affected communities and provide evidence of the experience of illness and disability. This approach emphasizes the performative power of personal storytelling and the need to witness, but risks to promote a reading of autobiography as a social good rather than as a complex, mediated and cultural practice. Specifically, what is insufficiently accounted for, is the role of mediality and materiality in autobiographical practices and politics of chronic illness. My project is a nuanced study of autobiographies of two chronic conditions: Long covid, the continuous illness after an infection with covid-19, and the chronic condition of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) are contested and debated in polarized ways in contemporary biomedicine and culture, leading to stigmatization and reduced quality of care for those affected. I closely examine a selected number of emerging autobiographical forms such as collective storytelling, virtual exhibition, and artistic microblogs which have been published in Germany and in the US (2015'Äì2023). By analyzing new strategies of communicating illness experience I ask how these media forms and material practices affect and are affected by politics of chronic illness and disability. I will integrate a wide variety of methodological approaches from media studies and concepts from disability studies and medical humanities to claim that closely examining mediated and material practices of autobiography opens overlooked relations between illness, media and politics that are obscured by the focus on representation. The project aims to reframe autobiography within questions of stigmatization and inequality and to reconsider how autobiography is conceptualized and approached in medical humanities more generally. Combined with innovative approaches of public engagement, the project seeks to impact the cultural bias against unexplained illness and to expand my transdisciplinary research expertise at the intersection of cultural studies and medicine.",,2025,UNIWERSYTET WROCLAWSKI,153949.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Poland,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2024 +P23633,101003633,Rapid interaction profiling of 2019-nCoV for network-based deep drug-repurpose learning (DDRL),"We aim to identify approved drugs that can be repurposed for the treatment of 2019-nCoV using interactome profiling and deep-learning. We will deploy rapid high-throughput protein-protein interaction mapping and computational protein-RNA interaction predictions to chart the coronavirus host interactome network (CoHIN), which will become a public resource for translational and basic coronavirus research few months after project start. CoHIN will serve as input into an existing deep-learning model to identify approved drugs that are likely effective against 2019-nCoV, which will be validated in in vitro and in vivo systems. In the second stage we will experimentally determine the matrix of viral protein alleles vs. variants of the interacting human proteins to understand how human and viral natural variations jointly mediate disease severity in different individuals. These data will be integrated with epidemiological and human genomics data to improve risk management and improve preparedness for future coronavirus outbreaks. Overall, we aim to achieve the following objectives: - Map the protein interactome of 2019-nCoV and related Coronaviridae with their human host - Generate the allele interaction matrix and relate differences to epidemiological data - Develop a microarray-based patient screen to detect exposure to 2019-nCoV and identify immunogenic epitopes - Identify 10 approved drugs that are most likely efficient against 2019-nCoV using network integration and deep-learning - Validate drug candidates in in vitro and in vivo systems",,2024,HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH,1341392.15,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Prophylactic use of treatments",2020 +P23634,101003551,EXaSCale smArt pLatform Against paThogEns for Corona Virus,"The EXSCALATE4CoV (E4C) project aims to exploit the most powerful computing resources currently based in Europe to empower smart in-silico drug design. Advanced Computer-Aided Drug Design (CADD) in combination with the high throughput biochemical and phenotypic screening will allow the rapid evaluation of the simulations results and the reduction of time for the discovery of new drugs. Against a pandemic crisis, the immediate identification of effective treatments have a paramount importance. First, E4C will select through the EXSCALATE platform, the most promising commercialized and developing drugs safe in man. Second, select from >500 billion molecules new pan coronavirus inhibitors. The huge computational resource, therefore the activities will be supported and empowered by three of the most powerful computer centers in Europe: CINECA, BSC and J√úLICH. The Swiss Institute of Bioinformatics (SIB) will provide the homology 3D models for the viral proteins. The Fraunhofer IME will provide the BROAD Repurposing Library and biochemical assays. Phenotypic screenings will be run by KU LUEVEN to identify molecules capable of blocking virus replication in in vitro models. IIMCB and ELECTRA will determine the crystal structure of at least one coronavirus functional proteins to evaluate the structural similarities with other viral proteins. EXSCALATE4CoV consortium will identify safe in man drugs repurposed as 2019-nCoV antiviral and will propose to the EMA innovation task force (ITF) to define a preliminary development strategy and a proposal for a registration path. The E4C project will share promptly its scientific outcomes with the research community by using established channels: ChEMBL portal for the biochemical data, the SWISS-MODEL portal for the homology models of viral proteins WT and mutants, the Protein Data Bank for the experimentally resolved protein structures, the EUDAT for the data generated by in-silico simulations and the E4C project website.",,2021,DOMPE FARMACEUTICI SPA,3238253.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P23635,101023459,Poplar Fiber Based Sustainable and Antibacterial Face Mask Filtration Media,"Among top ten current N95 producers, only one of them is EU-origin company. Europe needs to act to develop sustainable face masks to lead the fabric filtration industry, which will be worth in excess of 2.7 billion Euros in 2024. Due to ongoing coronavirus pandemic, consuming billions of face masks around the globe resulted not only plastic pollution, but also created a shortage on the melt-blown polypropylene (PP) supply chain, which is the mainly used filtering medium. PP is a petroleum-based polymer and doesn'Äôt have antibacterial activity. The ideal solution to this problem would be using a sustainable and antibacterial filtration media that can effectively filter ultra-small particles such as coronavirus itself. To address the challenge, I have formulated an innovative and interdisciplinary project based on my research experience to develop filtration media using sustainable and antibacterial poplar fibers that aligns with The European Green Deal action plan. After developing poplar webs, I will utilize Grado Zero Espace's (GZE), expertise to create commercial surgical masks and filtering facepiece respirators (FFP). The significance of developing Coronavirus-specific project is clearly emphasized in the European Research Area Corona Platform. Developing surgical masks and FFPs prototypes from a sustainable material not only contributes Sustainable Development Goal of EU, but also could lead higher-added value products, responding the global need for face masks in pandemic situations.",,2023,GRADO ZERO ESPACE SRL,222002.33,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P23636,101132473,Setting up a coordinated surveillance under the One Health approach,"The majority of new emerging infectious diseases that affect humans are zoonoses. The factors that drive the emergence and spread of zoonotic diseases are complex and include climate-related, ecological, political, economic and social factors. Animal health, human health and the environment are interconnected, and different ecosystems across Europe are changing in different ways.There is a need for more rapid and effective responses to zoonotic diseases. This is achievable with a conceptual shift from siloed health approaches towards One Health practices across disciplines, sectors, and agencies. The surveillance on the animal health side and in the environment needs to be scaled up to set up a One Health surveillance for emerging and re-emerging pathogens. This can only be carried out by Member States that implement the Union policies at national level, but optimally in collaboration across countries, as the threats are cross-border health threats. OH4Surveillance supports the participating countries to set up and scale up One Health surveillance to priority pathogens in an efficient, coordinated and collaborative manner. The scope of OH4Surveillance is limited to One Health surveillance aiming to protect public health through the early detection of emerging and re-emerging zoonotic pathogens in animals and environment. The setting up and scaling up activities include capacity building and surveillance activities, and is done in close collaboration with EFSA and ECDC as well as with related other projects. OH4Surveillance supports the policy priority to be better prepared to respond to cross-border health threats. OH4Surveillance contributes to the achievement of the EU4Health Programme'Äôs general objective of protecting people in the Union from serious cross-border threats to health and strengthening the responsiveness of health systems and coordination among the Member States.",,2026,STATENS SERUM INSTITUT,16403285.8,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Denmark,,Epidemiological studies,Disease surveillance & mapping,2024 +P23638,101112724,Implementation of Pandemic Preparedness Plan using Integrated Genomic Surveillance programs.,"The COVID-19 pandemic has changed the landscape of public health priorities and flagged the need for a global pandemic preparedness plan to address the current and upcoming health emergencies. Creating a European Health Emergency and Preparedness Response Authority (HERA) is the cornerstone of the European plan to prevent, detect, and rapidly respond to health emergencies. The HERA incubator grant boosted the national drive in capacity building in genomic and molecular microbiology. The Laboratoire national de sant√© (LNS), Luxembourg, and the National Institute of Public Health (NIPH), Romania, have agreed to initiate the (PANDOMIC) partnership that includes the Cantacuzino NMMIRD as an affiliated Romanian entity. This partnership aims to ensure complementarity and knowledge sharing in microbial genomics and downstream data analysis to develop a robust national integrated genomic surveillance program. A lesson from the COVID-19 pandemic was that cross-border collaboration adds value to public health measures, especially regarding laboratory diagnosis and surveillance systems. Our plan is implemented through a structured work package program led by LNS to expand the current WGS capacities to cover other viral pathogens of pandemic potential such as influenza, while building these capacities either in new sites (Romania) or introducing a new sequencing technology (ONT). The PANDOMIC will address the antimicrobial resistance concern by adopting a one health approach, in which LNS will showcase the integration of human, animal, and environmental bacterial genomic data to provide a comprehensive genomic map of AMR in Luxembourg. A significant component of this project is establishing a data hub and a biorepository that will gather genomic data with other metadata such as clinical data and infection outcomes which would be a vital input for any public health action during pandemics and allow interoperability among a potential public health laboratories alliance.",,2025,LABORATOIRE NATIONAL DE SANTE,3140976.7,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Luxembourg,,Epidemiological studies,Disease surveillance & mapping,2023 +P23639,101102070,Union and National Capacity Building 4 IntegraTED Surveillance,"The global crisis generated by the COVID-19 outbreak has revealed that the public health preparedness and responses to pandemics need to be urgently improved at European level. UNITED4Surveillance will contribute to the implementation of the new Health Security framework under the health union regulation on serious cross-border tThe global crisis generated by the COVID-19 outbreak has revealed that the preparedness and responses to pandemics need to be urgently improved at European level. UNITED4Surveillance will contribute to the implementation of the new Health Security framework under the health union regulation on serious cross-border threats to health, and support the implementation of the ECDC long term strategic framework for the period of 2022-2025, in relation to unlocking existing and new data sources for more comprehensive EU/EEA infectious disease surveillance, prevention, and control, and contributing to surveillance capacity building within Europe and beyond for better global health security. Representing 24 countries in Europe, UNITED4Surveillance gathers expertise in public health, (clinical) microbiology, epidemiology, and data-science, over the domains of public health, animal, and environmental health, thereby creating a strong network in integrated surveillance for infectious disease prevention and control. Our general objectives are to support in strengthening national integrated surveillance systems and scaling-up to EU level and to improve national surveillance systems by integrating different sources of electronic health data and digital registers/databases, thereby enhancing EU/EEA surveillance system. UNITED4Surveillance will propose a Roadmap to implementation of integrated surveillance at Member State and Union level which will 1) contain gaps and needs analysis, 2) integrate (inter)national polices, 3) identify and pilot promising approaches, 4) disseminate best practices and 5) share experiences and knowledge through capacity building.",,2025,RIJKSINSTITUUT VOOR VOLKSGEZONDHEID EN MILIEU,7489590.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Policy research and interventions,2023 +P23642,101062851,"Feminist movements responses to the gendered impact of crises (Gender, Resilience and Activism in Crisis Europe)","The gendered effects of the current pandemic crisis 'Äì i.e. how the economic, social, and political problems prompted by the COVID-19 health crisis affect women, men, Lesbian, Gay, Bisexual, Transgender, and Intersex people differently 'Äì are amongst the most visible and significant ones, yet continue to be largely underestimated in the mainstream political, policy, and academic debates. Women have and will continue to endure the social, economic and political damage generated by the crisis, due to precarious work conditions as well as unpaid care and housework. In this context, feminist movements have been capable to (re)introduce contentious claims over the deep meaning of the crisis and its consequences, raising public concern over imperative issues such as gender-based violence, reproductive rights and the centrality of care and social reproduction work as the material basis to sustain life. Against the backdrop, GRACE investigates how feminist movements address the gendered consequences of the crisis by looking at the variation in mobilization opportunities, strategies and policy outcomes in two national cases: Italy and Spain. It does so by examining feminist movements in: a) online and offline strategic choices, tactical innovation and changes in mobilization style; b) forms of (re)organization in the physical and digital space; c) discourses and knowledge production adopted to influence institutional actors and public opinion. Based on a mix-methods and cross-national comparative research design, GRACE aims to enhance the understanding of gender inequalities across contexts, crises'Äô consequences, and the influence of feminist movements on public policy. In doing so, GRACE will produce crucial knowledge to academics and policy makers to understand how the current crisis management entrenches the power of particular economic and social orders, enables structures and mechanisms of gender privilege and multiple inequalities.",,2024,UNIVERSIDAD COMPLUTENSE DE MADRID,162006.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Gender,,,Spain,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2022 +P23644,101061550,Legitimate crisis management and multilevel governance,"LEGITIMULT assesses the impact of the measures taken by various international, national and subnational governments on multilevel institutions and intergovernmental relations in the wake of the Covid-19 pandemic. The project analyzes the effect of these measures on democratic governance, highlighting to what extent multilevel governance influences their impact on democracy, favoring a model of legitimate crisis management. It assesses all measures taken by 31 European countries in relation to their impact on multilevel governance through the creation of a new dataset highlighting how these procedures link to multiple orders of governance 'Äì WHO and EU above the states, and regional and local governments below the national level. The impact of these measures is analyzed through the lens of a variety of dimensions that characterize functional democratic governance (Rule of Law and Democratic Participation; Human and Minority Rights; Trust; Economic Sustainability). LEGITIMULT qualifies the different trade-offs required within and across these dimensions in order to effectively and quickly deal with a crisis such as Covid-19, while at the same time maintaining a level of democratic governance and ensuring that any limitations to democratic standards are limited. These final trade-offs within and between the different dimensions of democratic governance in crisis management are gathered in a set of policy recommendations, tailored to different recipients, and developed through extensive consultation with stakeholder groups throughout the project. Citizens, policy makers and practitioners are involved in the experimental phase of the project, where interactive learning and practical tools are tested but also co-designed and co-refined with relevant stakeholders in a participatory way. Policy recommendations and practical tools merge into a toolkit for legitimate crisis management, ready for use in possible future crises.",,2025,ACCADEMIA EUROPEA DI BOLZANO,2905040.39,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23645,101061272,"ROBUST Crisis Governance in Turbulent Times 'Äì Mindset, Evidence, Strategies","The focus of European post-pandemic politics is currently on enhancing system capacities for 'Äòbouncing back'Äô from crisis to normalcy. These efforts draw on resilience research, which has become the dominant paradigm in crisis management. However, there are broad governance challenges that the resilience approach fails to consider. Centrally, how can European societies harness flexible adaptation and proactive innovation to deliver effective crisis responses in situations, where going back to the way things were is neither possible nor desirable? And how can democratic institutions uphold core values such as democracy, the rule of law, and fundamental rights in the face of crisis-induced turbulence? To address these challenges, the ROBUST project aims to set in motion a paradigm shift from 'Äòresilience'Äô ('Äòbouncing back'Äô) to 'Äòrobustness'Äô ('Äòbuilding back better'Äô) as the central principle of future crisis governance. The project breaks new ground by operationalizing the concept of robust crisis governance and investigating such responses empirically. We combine historical and comparative analysis at EU, national and local levels to gather a multi-dimensional data set out of which we identify the configurations of factors that drive (or block) robustness in crisis governance. The project studies responses by EU institutions and eight European countries to three recent crises (the financial, refugee and COVID-19 crises) to understand general patterns in system-level crises response, while we also conduct in-depth studies of localized COVID-19 responses 'Äòon the streets'Äô of 16 European localities to understand how EU, national and local crisis responses interact and are experienced by citizens. On this basis, the project delivers the elements of a new mindset along with policy recommendations for enabling the robust crisis governance of the future, all anchored in a learning hub that will serve as the social engine of the paradigm shift envisioned by the project.",,2026,ROSKILDE UNIVERSITET,2905175.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Denmark,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2022 +P23646,101063545,Legitimate Emergencies: Reconciling Liberal Rights and Democratic Authority in Times of Crisis,"This project will perform a realist analysis of emergency politics. More specifically, it will give a realist account of what states of emergency reveal about the nature of political legitimacy. This will be achieved through a mixture of history of political theory, critical analysis of competing recent approaches to emergency, and an empirical study of the political crisis caused by the COVID-19 pandemic. At present, political realists controversially argue that emergency politics expose how liberal theories of legitimacy are excessively divorced from reality. Their argument, however, remains underdeveloped in three key respects. In the first place, they seek to ground their claims in a broadly Nietzschean worldview, yet they do so in a manner that conspicuously jars with what Nietzsche himself writes about situations of emergency. Second, the realist literature fails to critically engage with recent liberal theories of emergency (and vice versa). Finally, realists neglect a wealth of relevant literature in jurisprudence, which has not yet been brought to bear on the debate in political theory. By addressing each of these lacunae, this interdisciplinary project will formulate a robust realist theory of emergency, one that will then be empirically applied to the states of emergency declared in response to the ongoing COVID-19 pandemic. The results of the project will be published in the form of a monograph.",,2025,UNIVERSITEIT VAN AMSTERDAM,202633.92,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P23647,101079900,Support Through Ethno-psychosocial approaches and PM+ for migrants,"Migrants have been among the most affected by COVID-19, exacerbating their prior vulnerabilities and worsening their mental health (MH) state. Even before the pandemic, however, public MH systems across Europe have been struggling to respond adequately to migrants'Äô MH needs, as MH professionals are a scarce resource, often ill-equipped to deal with people with a different cultural background. Hence, the STEP IN project will build the capacity of non-MHPSS professionals who are in contact with particularly vulnerable migrant populations (e.g. refugees and asylum seekers, women, adolescents and young adults, single-headed households, people affected by migration processes, Roma communities) in Italy, Greece and Romania to deliver the culturally appropriate Problem Management+ (PM+) programmes, embedding a ethno-psychosocial approach, to address mental and psychosocial health problems, including anxiety and depression, commonly found in individuals affected by adversity. The project will also evaluate the feasibility of PM+ to address target groups'Äô specific vulnerabilities through a Proof of Concept phase, eventually proposing evidence-based recommendations for scale-up in the selected locations and in other Member States. Networking and sharing opportunities will be ensured to further support replicability in other locations. In the short-term, the project will contribute to an improvement in the prevention of MH issues in migrant populations by: 1. equipping non-MHPSS professionals working with them with a flexible and affordable methodology; 2. raising the awareness of key stakeholders on the effects the pandemic has produced over migrants and the urgency to tackle them before they require specialised care; 3. providing evidence on effective approaches to improve the well-being of migrant populations. In the long-term, this would translate in reduced burden over MH public systems and enhanced public health actions.",,2024,SOS VILLAGGI DEI BAMBINI,384627.87,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P23652,101106861,The livEs of Real woRld dAta (TERRA),"Real-world data (RWD) refer to routinely collected data relating to patients'Äô health status and the delivery of health care originating from a range of sources other than traditional clinical trials. Electronic health records, patient registries or personal information collected from wearable devices are all examples of RWD. The Covid-19 pandemic saw the expansive use of RWD. Governments used these data to monitor populations'Äô health, while industry and drug regulators relied on RWD to assess the effectiveness of Covid-19 vaccines. Many of these RWD came from Israel and its data repositories. However, constructing the 'Äòreal-world'Äô through data is not a simple task. Producing data takes work from database curators, researchers or policy-makers, while it entails making decisions about what and who to include in the data to represent the 'Äòreal-world'Äô. In other words, producing RWD means representing, and enacting, versions of the 'Äòreal-world'Äô, while creating populations. Taking Israel as an empirical case study, TERRA aims to crack open the concept of RWD. Combining a literature review and an ethnographic study, TERRA has four objectives: 1) To map the emergence of the concept of RWD; 2) To develop an empirical analysis of the production, curation, uses and governance of RWD; 3) To build a conceptual framework to understand and theorize the making of population and value through RWD; 4) To deliver a series of innovative dissemination events aimed at engaging the public and key stake-holders with RWD and its implications for practice. As lives are being datafied through RWD, we must critically investigate how such data are produced from individuals'Äô bodies. Specifically, when data are understood to capture the 'Äòreal-world'Äô, we must interrogate what and who is represented through these data, because this shapes who can be treated and governed, with what, and in which ways.",,2026,BEN-GURION UNIVERSITY OF THE NEGEV,218586.42,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Israel,,,,2024 +P23656,190110623,"AlkaBurst2.0 'Äì A game changing bioreactor for sustainable production of active pharmaceutical ingredients in a consistent, traceable and low cost approach","Alkion, a revolutionary biotech company, is developing a breakthrough biorefinery to produce top quality active pharmaceutical ingredients (API) and extracts in plants in a sustainable and cost-effective way. Our core technology combines our disruptive patented automated bioreactor-AlkaBurst2.0 with unique knowhow on gene expression methods, culture media and extraction. Our process offers high productivity and a low carbon footprint. The pharma industry is carbon intensive with recurring problems of quality & safety. Moreover, many critical APIs are outsourced to Asia to cut costs. AlkaBurst2.0 allows a local standardised production of safe & clean APIs in its automated process saving 75% time, 80% space, 95% electricity, 98% water. We first validated the production for Covid-19 natural vaccine adjuvants QS21/7, cannabinoids & certain recombinant proteins for the urgent market demand. We need 'Ǩ7.5M to build & validate our pilot and expect to generate 'Ǩ125M revenue by 2028 with 105 job",,2024,ALKION BIOINNOVATIONS,2475000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Health Systems Research","Medicines, vaccines & other technologies",2022 +P23657,101056988,Strengthening voluntary non-remunerated plasma collection capacity in Europe,"The Covid-19 crisis has shown how vulnerable the world is in supply of life-saving medicines. Plasma-derived medicines, particularly immunoglobulins, Today face shortages in Europe. Simultaneously, there is an imbalance in the global collection of plasma needed for the products, with a high dependence of plasma coming from the U.S. The SUPPLY project therefore aims to increase and strengthen the resilience of plasma collection in the EU to enable a stable and adequate supply of medicines in Europe. A substantial part of plasma collection in the EU is conducted by the non-profit blood establishments (BEs) from voluntary non-remunerated donors, but not at the level needed. This project will focus on how BEs can improve and build up voluntary non-renumerated plasma collection programs and make them more efficient. Emphasis will be paid to maintaining donor safety in a way that benefits donor health and plasma quality intended for production of medicinal products. The project will evaluate current legal frameworks and policies in the EU on plasma collection and tender models to facilitate this process. Since plasma demand comes from the use of immunoglobulins, it is vital that its use is appropriate and prioritisation is properly guided. The SUPPLY project, led by the European Blood Alliance, will be carried out by a large European consortium with broad and complementary expertise relating to all aspects in blood and plasma collection, processing and medicinal use. The main project outcome is a set of recommendations and guidance for BEs, competent authorities, medical societies and other professional stakeholders to support them in being able to increase plasma collection in the EU by the public health sector and achieve optimal availability of plasma medicines for patients both in a general situation as well as in times of crises. This project will therefore contribute to the EU becoming more strategically independent in its need for plasma medicines.",,2024,EUROPEAN BLOOD ALLIANCE,1133525,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,Health Systems Research,"Medicines, vaccines & other technologies",2022 +P23658,101059332,RRR-XAI: Right for the Right Reason eXplainable Artificial Intelligence,"Deep Deep Learning (DL) is a form of machine learning (ML) that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. This hierarchy allows a DL model to learn complicated concepts by building them out of simpler ones. A graph of these hierarchies would be many layers deep, and thus its name. A Deep neural network (DNN) is based on an artificial neural network model, and its core strength is that there is no need for human assistance to formally specify all the knowledge that the model needs. This makes DNNs represent the state of the art in Artificial Intelligence (AI). Despite their top performance and ubiquity of applications (from Healthcare to autonomous cars), DNNs suffer serious shortcomings. First, DNNs are considered black box models, i.e., with complex and opaque algorithms, hard to interpret and diagnose. Second, they suffer from bias, and the testing protocols for automatic recognition are not fair, as they learn patterns in the data that are not correlated to the output; e.g. they may focus on areas outside the lung in X ray images to predict the presence of COVID-19. Although DNNs outperform many other methods, they often are not right for the right reasons (RRR). RRR-XAI tackles this mismatch and bridges this gap through a tight integration of DL and symbolic AI, with the principal objective of making DL explainable. To achieve this I will follow the rationale behind XAI under the RRR philosophy and perform analyses to understand two types of phenomena that cause trouble in DNNs. Second, I will use: 1) Domain knowledge expertise as supporting evidence to explain a particular model output; 2) Neural-Symbolic computation to communicate the explanation of such phenomena in natural language. I will study two practical use cases where supporting explanations of the model output are critical: a) COVID-19 prediction from chest X-Ray images, and b) Weapon detection in alarm systems and crowds from images.",,2024,UNIVERSIDAD DE GRANADA,163659.87,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Spain,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P23659,959379,Video Livestreaming Has Never Been Easier And Can Help Us Stay Connected During COVID-19,"Livestreaming offers many opportunities for marketing and information but its uptake is limited due to time-consuming and expensive systems. Video streaming is the fastest growing way that audiences are consuming content. Challenges associated with video live streaming include bandwidth issues. The global video streaming software market is expected to rocket to over 'Ǩ9 billion by 2023. Contentflow provides a complete livestreaming platform ranging from a single hub for Contentflow is already in the process of assisting in the critical situation with COVID-19. For instance, just in March 14th 2020, Contentflow has helped the Bavarian City Championships to be held virtually instead. Contentflow is the only technology that offers flexibility for different formats, a cloud-based engine that allows exporting and live-clipping of live streams, automated subtitles in all major languages, white label solutions, parallel live-streaming, player functionality, live stream editing, streaming in Full-HD and restreaming to all major social platforms (e.g. Facebook, Twitter, YouTube) and advanced analytics. Contentflow'Äôs advanced analytics allows its users to get access to the vital information on their audience so that they can provide optimum content. Contentflow is helping companies to be able to continue sharing information via live streaming and putting events online during the Corona Virus outbreak. We have received a 'Ǩ2 million seed round investment from Speedinvest, VC Fonds Technologie Berlin, Betaworks, and Japanese Akatsuki Entertainment Technology Fund as well as other angel investors. Our clients will help us make revenues of 'Ǩ694,000 in 2020. Contentflow will help democratize information in Europe by providing a reliable video streaming service that can reach anyone, the ability to prove more transparency to voters, journalists and the public audience and opens political participation to even more target groups due to automated subtitles.",,2022,CONTENT FLOW GMBH,2600775.52,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,,,2020 +P23663,101026507,Staying at home - the interplay between behavioural synchronisation and physical distancing in prosocial behaviour,"The COVID-19 outbreak is a public health and economic crisis, unprecedented in human history and as the epidemic progresses, it becomes obvious that human behaviour plays a crucial role in curbing the epidemic spread. In liberal democracies, governments largely rely on the population'Äôs willingness to adhere to measures. Adherence to measures is framed as a prosocial act but the consequence - staying at home - isolates individuals from the collective and counteracts behavioural synchronization. This leads to competing effects on the levels of prosociality in a population. Understanding these dynamics is of great importance to evaluate the sustainability of measures but to date, there is no assessment of the influence on prosocial behaviour on the level of adherence to measures. To this end, I will numerically model prosociality in a population during a pandemic as a dynamical system. Here, prosociality is subject to a driving force (severity of pandemic), positive feedback through emotional synchronization (news, social media) and dampening (quarantine fatigue). To parameterize the model I will measure collective and individual levels of prosociality in a population using digital traces on social media platforms. By applying the LIWC method on, for example, a corpus collected from Twitter for different countries in the period before and during the pandemic, population levels of prosociality can be extracted. I will use the parameterized model to compare different liberal democracies and assess the combined impact of prosociality and non-pharmaceutical intervention measures on the prevention of the spread of COVID-19. To this end, I have established collaborations with eminent epidemiologists. Furthermore, I will implement a public monitor for prosociality (and other emotions such as anger) for European countries that will enable decision-makers to assess public sentiment in a timely and quantitative manner.",,2024,TECHNISCHE UNIVERSITAET GRAZ,196808.71,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions,2022 +P23665,190197515,"The first broad-spectrum treatment against pandemic-prone flaviviral infections: Dengue, West-Nile and Zika","WHO, governments and health institutes are urgently seeking methods to prevent future catastrophic flavivirus outbreaks affecting millions (annually >40% of the global population at risk, resulting in ~395M infections, >25,000 deaths of which mainly children, 750.000 disability-adjusted life years and >'Ǩ9B direct & indirect costs). As there are no effective treatments or vaccines available, ATLAS will provide a breakthrough in broad-spectrum antivirals: the first-in-class drug to combat the global health emergency of flaviviral infections. In the ATLAS project, Protinhi will finalize clinical trial-enabling studies and pharmaceutical development and obtain proof-of-concept in humans by conducting Phase I and Phase IIa clinical trials against the most common flavivirus: dengue. This will put the company in an excellent position to attract interest from pharmaceutical companies (e.g. Gilead, J&J, MSD) for a strategic partnership for late clinical development and commercialization.",,2026,PROTINHI BV,2674998.93,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Flaviviridae,,,,,,,,,Zika virus disease | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Therapeutics research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2023 +P23666,101137006,Development and characterization of a pan-flavivirus vaccine candidate,"Dengue, yellow fever, Zika, and West Nile viruses are mosquito-borne flaviviruses and global public health burdens that infect half a billion people annually, causing 250,000 deaths, and threaten nearly the entire human population. In a context of human-driven global changes, these threats will intensify with larger and more frequent epidemics, potentially leading to pandemics, will expand with geographic spreading of the mosquito vectors, and will multiply with the likely emergence of yet-unknown flaviviruses. Improving pandemic preparedness and response to these emerging and re-emerging diseases is a top priority both for the EU and WHO. However, there are no effective interventions against all flaviviruses and current vaccines targeting flaviviral proteins have severe safety issues. FLAVIVACCINE'Äôs high-impact/low-risk/disruptive ambition is to develop a novel, broad-spectrum, mosquito saliva-targeted vaccine candidate that protects against multiple different flaviviruses and is ready for clinical evaluation by building upon an experimentally-validated proof-of-concept. FLAVIVACCINE will define the immunogenicity of the pan-flavivirus target, develop and characterize a vaccine candidate against multiple flaviviruses, and prepare it for clinical evaluation. To reach these goals, FLAVIVACCINE creates a unique interdisciplinary environment of ten public and private institutions, including Universities, Research Institutions and a Vaccine Developer, from seven countries to cover all the required scientific expertise and knowledge in cell biology, virology, immunology and vaccinology. The pan-flavivirus vaccine candidate that will be validated against dengue, yellow fever, Zika and West Nile diseases in several preclinical models, together with the knowledge and networks resulting from FLAVIVACCINE, will have short- and long-term impact on the EU ability to combat epidemic and pandemic viral threats, and protect communities and citizens in the EU and around the world.",,2028,INSTITUT DE RECHERCHE POUR LE DEVELOPPEMENT,16738471.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Flaviviridae,,,,,,,,,Zika virus disease | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Vaccines research, development and implementation",Pre-clinical studies,2024 +P23667,101095444,Pandemic literacy and viral zoonotic spillover risk at the frontline of disease emergence in Southeast Asia to improve pandemic preparedness,"The PANDASIA project addresses the call by providing a framework that will increase our understanding of the biology of viruses with emerging infectious disease potential and their interaction with humans, animals and the environment and translating this understanding into proactive preventative actions. Such research is crucial for providing evidence-based knowledge and tools for better integrative public health measures for local and national actors. We will develop models to identify and predict drivers of disease emergence, which will be evaluated with real world data, refined and used to develop health and pandemic literacy intervention strategies that reduce risk of future viral emergence, thereby reducing the burden of zoonotic spillover to human health. Since pandemics arise at a local level it is important to engage with local communities and health, environment and agriculture authorities to improve their health and pandemic literacy to ensure adequate preparedness and vigilance for future spillover events and human, animal and environmental health threats. Understanding spillover dynamics and threats at local levels in emerging disease hotspot areas, such as Southeast Asia, is important for the European Union to improve preparedness and the ability to respond quickly to health emergencies and cross-border threats. The identified drivers are likely generalizable to other emerging infectious disease hotspots in the region and if successfully implemented in SE Asia could be adapted to other hotspot regions, such as in South America and Africa.",,2027,NORGES MILJO-OG BIOVITENSKAPLIGE UNIVERSITET,3706000.64,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Norway,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Vector biology | Vector control strategies | Disease transmission dynamics | Disease surveillance & mapping,2023 +P23670,101077640,Universal building blocks for antigen presentation to uncover the flavivirus-directed antibody response,"Flaviviruses are a tremendous burden on global public health. The genus consists of yellow fever virus, dengue virus, and zika virus amongst others. These viruses threaten more than half the global human population and are spreading into new territories. The recent zika virus pandemic stresses the need for a suitable protein engineering toolkit to enable swift development of emerging flavivirus antigens for structural studies, serology and vaccine development. Moreover, the structural determinants of a neutralizing polyclonal antibody response are currently not well understood, in large part for a lack of suitable methods to address the complex interactions of multiple antibodies directed against a heterogeneous, glycosylated viral antigen. With FLAVIR I will use my unique expertise in both mass spectrometry and electron microscopy to develop a comprehensive structural proteomics toolkit for in-depth profiling of the neutralizing antibody response against flaviviruses. Using a combination of novel mass spectrometry-based antibody sequencing techniques, glycoproteomics profiling and electron microscopy, we will uncover how the polyclonal antibody response against flaviviruses is directed by key structural determinants of the Envelope glycoprotein that is displayed on the surface of infectious virions. We will develop new strategies to produce prefusion stabilized E-dimers and ultimately reconstruction of full icosahedral flavivirus-like particles from soluble components. The outlined strategies will be tested and streamlined for broad applicability across the flaviviruses so that it can be swiftly adapted for emerging species and strains. We will characterize our designs with state-of-the art mass spectrometry methods (native MS, mass photometry, HDX-MS) and electron microscopy. We will use these optimized antigens to uncover the role of antigen glycosylation in antibody binding, profile the serum antibody repertoire directed against the E-antigen and map ou",,2028,UNIVERSITEIT UTRECHT,1856250,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2023 +P23672,101003713,Development and validation of rapid molecular diagnostic test for nCoV19,Rapid development of a molecular diagnostic test for Corona virus nCoV19 for near patient testing,,2021,HIBERGENE DIAGNOSTICS LIMITED,1015449.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P23673,101094685,Integrating Multi-Disciplinary Expertise in a Learning and Adaptive European Pandemic Preparedness System,"The COVID-19 pandemic has exposed a global need for accelerating research, improving surveillance, and efficiently developing countermeasures against pathogens with epidemic and pandemic potential. LEAPS aims to demonstrate the value and feasibility of a pro-active policy-supporting strategy for genomic surveillance and for pandemic preparedness and response, by delivering a system-wide stakeholder-validated proof of concept, validated in 4 EU countries, of a learning and adaptive European pandemic preparedness system against pathogen X.'ÄØ LEAPS will fill the gaps observed by global, EU (HERA) and national stakeholders in pandemic response by demonstrating the feasibility of combining genomic One Health surveillance, with genomic epidemiologic modeling for detailed pathogen understanding and precise public health intervention design. LEAPS formalizes dynamic health emergency threat assessment linked to the initiation of governance mechanisms to enable timely decisions in crucial, early stages of an outbreak. 'ÄØLEAPS will develop protocols and models for accelerated medical countermeasure development, availability and accessibility. Based on resulting highly effective intervention strategies, timely countermeasure access and governance mechanisms, model-based policy support is proposed to health authorities for effective, implementable, stakeholder co-created epidemic response scenarios against pathogen X. Scenarios are evaluated on health, socio-economic, and sustainability impact. LEAPS brings together a unique multidisciplinary team with optimal complementary expertise and experience. LEAPS will interact regularly with medical and scientific communities, HERA and health authorities in order to disseminate relevant and accessible information, and during non-emergency periods LEAPS will validate a roadmap for large-scale implementation of LEAPS methodology by EU level, and national authorities and stakeholders in an ecosystem of interlinked actors.",,2027,KATHOLIEKE UNIVERSITEIT LEUVEN,3179576,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Policy research and interventions,2023 +P23674,101057795,Building a European strategic Research and Innovation Area in Direct Synergy with EU and International Initiatives for Pandemic Preparedness,"The COVID-19 pandemic has confirmed and further highlighted the importance of planning and investing in research and innovation well before a health crisis occurs. For this purpose, the main goal of BE READY is to build a consolidated European Research and Innovation Area that provides the foundation of the candidate European partnership for pandemic preparedness so to improve the EU's preparedness to predict and respond to emerging health threats by better coordinating funding for research and innovation at EU, national (and regional) level towards common objectives and an agreed Strategic Research and Innovation Agenda. The Partnership is expected to build on existing pandemic preparedness networks, and work in synergy with the Health Emergency Response Authority (HERA), in close collaboration with ECDC, EMA and other relevant international and European actors. BE READY is composed by 24 organisations from 15 countries with complementary expertise and policy area ranging from Public Health Organisations, Ministries (of Science, University, Health, Innovation or Environment) and Research Performing Organisations that ensures a cross-cutting, interdisciplinary Global Health and One Health approach.",,2025,INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE,2138816.58,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,,,2022 +P23675,101137506,New AntiVirals for Infections with Pandemic Potential,"For infectious disease management and control, vaccines are considered golden countermeasures. but are not the most adequate tool for mitigating the early effects of an outbreak. Taking the recent COVID-19 pandemic as an example, access to broadly applicable therapeutic antivirals would have had a major impact, decreasing the human toll of the disease, and alleviating the burden carried by health care systems. It is urgent to focus resources and efforts on the development of broad spectrum antiviral drugs against unknown pathogens. The NAVIPP consortium aims to strengthen the EU'Äôs readiness and response capacity to viral threats by assembling an international R&D platform for antiviral drug development against pandemic prone pathogens. The consortium will implement a strategic, multi gear R&D and clinical roadmap for the identification, optimisation, preclinical and clinical investigation of broad spectrum antivirals against pathogens with epidemic or pandemic potential. In particular, the consortium will design compounds library with increased diversity to be tested in high-throughput assays against highly pathogenic viruses. Hits coming from this exercise, as well as assets that have demonstrated antiviral activity in previous exercises, will be assessed against a larger virus panel. Validation of the antiviral efficacy of the hits will be done in state-of-the art ex vivo models to prioritize compounds going to in vivo proof of concept studies. Mode of action and target will be also interrogated. Additionally, the implementation of an adaptive platform trial will enable early clinical investigation of 3 antivirals and will pave the way for clinical testing of other antivirals. Finally, the project will investigate new innovative and improved delivery systems of antivirals through nano conjugation. Ultimately, this project will deliver a pipeline of broad-spectrum anti-viral candidates and in the longer term contribute to European preparedness for emerging threats.",,2028,EUROPEAN RESEARCH INFRASTRUCTURE ON HIGHLY PATHOGENIC AGENTS,8195532.4,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Therapeutics research, development and implementation",Pre-clinical studies | Therapeutic trial design,2024 +P23676,101102440,Consolidation of WGS and infrastructure processes in surveillance and outbreak investigation actvities,"In the course of the first project round, the focus on national infrastructure and capacity up-scaling enhancing whole genome sequencing (WGS) and/or reverse transcription polymerase chain reaction (RT-PCR) to respond to the COVID-19 pandemic and future health threats (HERA) set a solid but challenging basis for the enhancement of processes in national Health Agencies and public analytic facilities. In this follow up project, the consolidation of WGS and RT-PCR activities aiming to ensure the sustainable use and integration of enhanced infrastructure into routine surveillance and outbreak investigation activities, in synergy with relevant on-going work at international level is the key priority. Identified challenges and mid-term aims were identified and will contribute together with the involvement of relevant and high-level stakeholders to a better workflow, enhanced capacity and sustainable and manageable use of the provided infrastructure on the long run.",,2026,AGES - OSTERREICHISCHE AGENTUR FUR GESUNDHEIT UND ERNAHRUNGSSICHERHEIT GMBH,4363644.91,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,Epidemiological studies,Disease surveillance & mapping,2022 +P23677,101103217,"Building resilient research ethics, Diagnostics and medicines regulatory capacity during routine and public health emergency periods","An effective and strong regulatory system for health technologies is critical, especially during epidemics and pandemic situations. The demand for rapid approval and application of a variety of health technologies including diagnostics and medicines during COVID-19 has reawakened the world to the urgent need to have resilient regulatory capacities that can respond in a timely manner with corresponding efficiency. National Medicines Regulatory Authorities and Research Ethics Committees are duty bound to prepare and be ready to respond in any health emergency. Through EDCTP-2-funded projects namely SMERT, PAVIA and ASCEND, substantial progress has been made on strengthening some procedures for clinical trial control and pharmacovigilance. These projects have enabled Tanzania to attain WHO Maturity level 3, making it a role model in East Africa. We now propose BREEDIME to further build our capacity in the context of epidemic and pandemic preparedness. BREEDIME will enable Tanzania to achieve rapid response clinical trial regulatory capacity for therapeutics, vaccines, and diagnostics; capacity for post-market evaluation and appraisal of health technologies; establish research ethics framework for electronic health data and materials storage, access and sharing within and outside the country; and establish a south-south learning centre in clinical trials regulatory and ethical review capacities. These objectives will be achieved through engagement of stakeholders in academia, civil society, public and government to generate evidence to inform new regulatory guidelines. Rwanda, which recently established her Food and Drugs Agency will become the first mentee under the BREEDIME south-south networking in ethics and medicines regulatory capacity building. The impact of the outputs of this study will be ensuring safety of pre- and post- registration health technologies in Tanzania and East Africa at large.",,2026,KAROLINSKA INSTITUTET,641612.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation | Research to inform ethical issues | Health Systems Research",Clinical trials for disease management | Therapeutics logistics and supply chains and distribution strategies | Vaccine trial design and infrastructure | Research to inform ethical issues in Clinical and Health System Decision-Making | Health leadership and governance,2023 +P23678,101132215,INTERnational Cooperation of high containment research infrastructures: from Epidemic Preparedness TO Response,"Emerging infectious diseases (EID) do not respect borders. They rank as global catastrophic risks for humanity, along with climate change and biodiversity loss. The COVID-19 pandemic showed how coordination of global research, through cooperation, and sharing of data and expertise, are crucial for efficient and effective preparedness to EIDs, and vital for a rapid response. Nevertheless, there are still major challenges limiting global cooperation among high containment laboratories (HCLs). HCLs are critical infrastructures for the development of medical countermeasures (e.g., vaccines and therapeutics) against high consequence pathogens. In order to fulfil its role, and given the global threat of EIDs, the European Research Infrastructure on Highly pathogenic Agents (ERINHA), together with its partners, proposes to establish and reinforce interactions with HCL research infrastructures (RI) worldwide, to strengthen pandemic preparedness and response capacities. INTERCEPTOR (INTERnational Cooperation of high containment research infrastructures: from Epidemic Preparedness TO Response), a consortium with key HCLs from Europe and across the world, will focus on access provision to HCLs, enhancement of the human capital of HCL, including in biorisk management, critical resources sharing, harmonisation and interoperability. The proposed actions will help ensure broader access to state-of-the-art HC facilities, while respecting the necessary biosecurity and biosafety constraints, and promote the establishment of a sustainable global network of HC RIs. By expanding access to HC RIs, strengthening the human capital base, promoting sharing of knowledge, skills and experience, and providing opportunities for common training programmes and staff exchanges, INTERCEPTOR will reinforce the next generation of HCL researchers and facility managers, and extend the opportunities for access to HCLs, required to push the boundaries of science and innovation in the field of EIDs.",,2026,EUROPEAN RESEARCH INFRASTRUCTURE ON HIGHLY PATHOGENIC AGENTS,3295768.3,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,,,2024 +P23679,101069764,"Prevention, mitigation, management of infectious diseases on cruise ships and passenger ferries","With vast experience, in-depth knowledge and established expertise in infectious disease prevention and control on passenger ships, HEALTHY SAILING consortium presents a comprehensive approach introducing innovative, multi-layered, risk and evidence-based, cost-effective tested measures for infectious diseases prevention, mitigation and management (PMM) differentiated for large ferries, cruise ships and expedition vessels. This approach covers: a) preparedness and response to known infectious diseases frequently occurring on passenger ships, diseases that have never occurred but for which preparedness is essential, diseases of unknown aetiology to ensure preparedness for future emerging pathogens/pandemics; b) the entire passenger/crew journey travelling from home to ship and returning, on-board, during shore-side visits; c) ship-board operations, shore-side company operations, port destinations and communities; d) a global perspective of project outputs towards communities and passenger shipping industry. Epidemiological studies, risk assessment, modelling for disease spread and aerosol/droplet dispersion and setting disease thresholds/alert levels will develop a scientific evidence-base and support production of evidence-informed guidelines on COVID-19 for ships/ports, passengers/crew vaccination, ventilation systems and expedition vessels'Äô medical operation needs. Development/testing of ship-specific syndromic surveillance, AI systems, decision support tools will contribute to early health threat detection on-board, risk-based proportionate responses, and healthy on-board environments. Toolkits for blended learning with hands-on training and technology induced behaviour change will further knowledge, awareness and compliance of all stakeholders. An integrated e-pass based on one-ID concept and toolkit predicting port response capacities will address port operation and community needs. A scientific international panel will promote a harmonized global approach.",,2025,PANEPISTIMIO THESSALIAS,3194561,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Greece,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience","Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures | Approaches to public health interventions",2022 +P23680,101120507,From Insightful Science to Innovative Health: Strengthening Translational Capacity and Talent Interoperability in Vaccine and Biologic Research & innovation,"Following the COVID-19 pandemic, biologicals and vaccines became regarded as salient pillars for disease prevention and control. However, strengthening preparedness for and response to health emergencies request more commitment and intersectoral cooperation between academia and industry to set up efficient strategies against diseases, whether through surveillance, detection, diagnosis, prevention, or treatment. VISION (Vaccine & bIologics reSearch & innovatION) intends to implement an intensive intersectoral and bidirectional knowledge/know-how transfer programs in order to reinforce vaccine and biologics development capacities with manufacturing, upscaling, or delivery capabilities among a consortium with Institut Pasteur de Tunis (Tunisia), Darnitsa (Ukraine), Torlak Institute (Serbia) and Connect'Äôinnov (Tunisia) as academic (AC) & non-academic (NA) widening members; Institut Pasteur (France) and Center for Genomic Regulation (Spain) as academic research non widening (NW) organizations; Merck (France) and Quantoom (Belgium) as NW&NA partners. VISION comes as a critical lever for R&I ecosystem feeding post-pandemic needs and matches the WHO mRNA Transfer initiative aiming to enhance widening production capacities and help achieving a comprehensive health coverage towards Sustainable Development Goals. VISION will in fine streamline the discovery, testing and production of biologics and vaccine candidates including mRNA-based technologies. VISION's main objectives are threefold: (i) endow Widening Talents with advanced knowledge and skills in Vaccine and Biologics Development, (ii) promote more impactful collaboration through training and mobility between AC and NA sectors towards an efficient high-performance translational R&I environment with an Open Science pillar, and (iii) ambition to make widening members a regional flagship for excellence in innovative research with increased biobusiness and entrepreneurship capacity and openness to the socio-economic sector.",,2027,INSTITUT PASTEUR DE TUNIS,2922929.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Tunisia,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2023 +P23681,101073821,Strategies and Technologies for United and Resilient Critical Infrastructures and Vital Services in Pandemic-Stricken Europe,"The COVID-19 pandemic has highlighted the importance of the continuity of vital services, has shown the need to work together for the common good. It has proven that a pandemic is not only a health crisis and that it does not only disrupt Critical Infrastructures (CIs), but that there is an extremely important link between the resilience of CIs and our societies. The economic crisis caused by the pandemic also provides a unique opportunity to jointly 'Äòbuild back better'Äô with the focus on sustainability and green recovery. SUNRISE will facilitate active collaboration of CIs across Europe to share best practices and jointly tackle future pandemics. By Q3/2025, this collaboration will result in a new stable working group for resilience to pandemics with at least 100 members. With a group of 4 CI authorities, 16 CI operators, 3 other CI stakeholders, 4 experts in Social Sciences and Humanities, 2 experts in epidemiology and climate extremes, and 12 security researchers and SW developers, we will: (1) Identify pandemic-specific vital services and CIs, their dependencies, risks, cascading effects, and effective measures to tackle them at European level. (2) Develop a comprehensive strategy (TRL8) and four innovative tools (TRL7) ensuring greater availability, reliability, security, robustness, trustworthiness, cost-effectiveness, climate-friendliness, and continuity of pandemic-specific vital services in Europe: Tools for risk-based access control, resource demand prediction and management, cyber-physical resilience, and remote infrastructure inspection. (3) Pilot the results in operational environments of the CIs while tackling some of their biggest pain points exposed by the current pandemic. (4) Promote our approach across Europe to ensure a united front and resilience of CIs to pandemics. We will carefully consider legal, ethical, societal, economic, and climate aspects, ensuring that our results address not only the needs of the CIs, but also those of our society.",,2025,ATOS IT SOLUTIONS AND SERVICES IBERIA SL,9256453.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2022 +P23682,101094188,Secretariat of Global research collaboration for infectious disease preparedness,"GloPID-R-Sec III is the Secretariat to the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R). Charit√© Universit√§tsmedizin Berlin (CHARIT√â) has decided to fulfil the role of Coordinator of the Secretariat, in close consultation with Fondation M√©rieux (FMER; previous Secretariat coordinator) and the University of Oxford (UOXF; continuing key technical partner). As GloPID-R is continuously evolving its organization and structure, so must the Secretariat evolve. GloPID-R Sec III provides the opportunity to move towards a collaborative leadership model, aligned with GloPID-R'Äôs vision, aiming to respond to the increased willingness from funders to work together, and to the increased work scope for GloPID-R and the Secretariat due to the lessons learned from the COVID-19 pandemic. The objectives and core activities of GloPID-R Sec III encompass: -Core organisational and secretarial services: To provide operational secretarial, organisational, and administrative support to the GloPID-R organisation; -Communication and stakeholder engagement support-oriented services: To implement, maintain and evaluate an effective external communications and advocacy programme to support communications with GloPID-R Members and stakeholders; -Technical support-oriented services: To support the further development and operationalisation of GloPID-R'Äôs strategy by providing expert technical and operational support to its Executive Board and Working Groups. Critically, to meet the expectations of GloPID-R, the Secretariat must continuously explore and implement key adaptations that improve the effective coordination between (inter)national funders and stakeholders for a rapid research response to public health emergencies. Thus, our work plan has been devised to adjust to the anticipated evolution of the alliance and to the changes that occurred during the previous funding period.",,2025,CHARITE - UNIVERSITAETSMEDIZIN BERLIN,1704844.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research | Research on Capacity Strengthening,Health leadership and governance | Cross-cutting,2023 +P23683,101062523,Reliable Epidemic monitoring And Control under geographic and demographic heTerogeneities,"The current COVID-19 crisis has highlighted the failure of existing epidemic monitoring techniques in timely predicting the epidemic situation and facilitating efficient policy recommendations. Because of being open-loop or linearization-based, these techniques cannot handle model and data uncertainties effectively. Designing a feedback mechanism to enable reliable, closed-loop epidemic monitoring is crucial but challenging because of the nonlinearity and heterogeneities of the epidemic spread process. The control mechanisms for epidemic mitigation are well-known, such as testing, lockdown, social distancing, etc. However, when, where, and to what extent should the health authority implement these policies depends on the accurate estimation and forecasting of the epidemic situation, which is very difficult with the classic observer design techniques. To alleviate the difficulties posed by these observers, an interdisciplinary approach of physics-informed neural network (PINN) in combination with system-theoretic tools is proposed in this project for closed-loop epidemic monitoring that can effectively cope with uncertainties. The task of PINN is to estimate the unknown nonlinearity (i.e., disease transmission rate) and epidemic parameters by using both the physics of epidemic spread (i.e., model) and the past epidemiological data. The closed-loop structure copes with the uncertainties and validates the estimation algorithm in real-time by predicting the future data and adjusting the epidemic model accordingly. The information received by the PINN-based observer will be utilized by the optimal controller to devise optimal policy recommendations under socio-economic constraints for epidemic mitigation. The closed-loop epidemic monitoring and control technique will be integrated to understand the geographic and demographic heterogeneities during epidemic outbreaks, which will significantly enhance the effectiveness of optimal policies.",,2025,KUNGLIGA TEKNISKA HOEGSKOLAN,305928,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Sweden,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2022 +P23684,101060774,"Resilient, sustainable and participatory practices: Towards the GLAMs of the commons","The outbreak of the pandemic created unprecedented challenges for galleries, libraries, archives and museums (GLAMs), which were already struggling during the last years with issues of underfunding, increased maintenance and operational costs and challenges imposed by over-tourism. The COVID-19 pandemic served as a wake-up call to rethink how cultural production and consumption are organized and articulated with different sets of actors and local contexts, towards safeguarding sustainability, access and the well-being of the sector, its workforce and surrounding communities. Long before the pandemic crisis, European cultural policy encouraged museums to embrace participatory governance and digitisation (European Commission, 2010 ), become more financially self-reliant and diversify their income-generating activities. It is thus vital to map pre-pandemic practices across the sector, to fully account the pandemic effects on the sector and to explore novel solutions that will inform GLAMs response and adaptation to the post-pandemic era, under a new conceptual paradigm that will advance GLAMs as the agents of change. GLAMMONS project aims to provide answers to the above challenges, fill gaps and advance research and policy employing the theory of the commons to i) provide an in-depth analysis and evaluation of ongoing shifts (with a specific focus on both pandemic-driven transformations and digitalisation) in the field of GLAMs, ii) explore and assess practices (concerning management, finance and participation) that emerge around small scale, community-led GLAMs and the possibility of transferring relevant knowledge to more 'Äúestablished'Äù and traditional ones to provide more sustainability to the sector. Rooted in a track record of internationally recognized research excellence and world-leading practice, GLAMMONS will deliver an ambitious work programme, mainly through a novel conceptual approach: the GLAMs of the commons.",,2025,PANTEIO PANEPISTIMIO KOINONIKON KAIPOLITIKON EPISTIMON,2859560,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Greece,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23686,101061575,"The enforcement of EU Competition Law in the pharmaceutical sector: before, during, and after a health crisis (learning from the COVID-19 Pandemic)","COMPHACRISIS will be carried out in line with the Pharmaceutical Strategy for Europe, under the supervision of Professor Imelda Maher at University College Dublin (UCD). The main question of the research is: what are the significant differences between normal, crisis and post-crisis EU competition law and policy in the pharmaceutical sector? Analysing the normal enforcement of competition law, evaluating the crisis enforcement of competition law, exploring the significant consequences of the crisis policies in the post-pandemic law and designing an Effective Health Crisis Competition Law Framework are specific objectives of COMPAHCRISIS. The European Union competition law enforcement and three member states (Germany, Italy, and Ireland) will be reviewed in COMPHACRISIS. To conduct the project, both the semi-structured interview method and doctrinal method will be used. COMPHACRISIS leads to significant improvement of my scientific profile, better networking with the research and industrial community through interviews, workshops, seminars and conferences, and helps me gain different skills such as project management skills, qualitative and quantitative skills, mentoring, grant writing, interview and analytical skills. I will also take some courses in Econometrics methods and Health Policy. I will be able to submit papers in English to leading international competition law journals and learn new research methods and teaching skills from my supervisor. The results of COMPHACRISIS will be published in prestigious journals, and I will present my research at well-known and international conferences. We will also organise two specialised workshops in UCD. Using social media and social networking tools to present the work is among the COMPHACRISIS communication activities. COMPHACRISIS will lead to a new approach in understanding the importance of competition law in the pharmaceutical sector during and after a crisis, and influence European policy-makers and legislators.",,2024,"UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN",215534,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Ireland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23696,101060107,Integrating Adaptive Learning in Maritime Simulator-Based Education and Training with Intelligent Learning System,"While all educational sectors have been affected by the COVID-19 pandemic, the vocational-oriented academic training components in higher education sectors have been more severely affected than others. For undergraduate and graduate students currently studying for a career at sea, the pandemic has led to suspension to their simulator training sessions, vocational learning opportunities and future careers. The simulator-based education and training domain, which forms the platform of skilled manpower supply for the maritime industry, is facing this unprecedented challenge to ensure the continuity of the educational activities and to cope with the constraints imposed by the pandemic. High-quality vocational education is the cornerstone of effective youth transitions into the labour market for the European society. The suspension of simulator-based training and tutoring sessions has led to concerns regarding whether the higher and vocational educational institutes can produce a sufficient and competent workforce who could adequately carry out on-board navigation functions safely and efficiently in the near future. By accounting for the needs, knowledge gaps and challenges faced by today'Äôs maritime education and training sector, the i-MASTER project aims to integrate emerging technologies in vocational education and training to develop an innovative Intelligent Learning System (ILS) with maritime learning analytics and adaptive learning function to facilitate both remote and on-site maritime simulator-based education and training. The i-MASTER solution will significantly enhance the effectiveness and accessibility of simulator-based education in the European society and further improve safety, security and performance of maritime operations of the future.",,2026,UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET,3286600,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P23702,101066680,(Re)Connecting Maritime Ecosystems: Geospatial Mapping of the 'ÄòSpaces of Flows'Äô in Port-City Regions,"How can policy tools and actions facilitate the sustainable development of the port-city regions to mitigate negative externalities of port activities, improve logistics efficiency, and help a more sustainable integration of the port in the hinterland and urbanised spaces, also considering the aftermath of the Covid-19 pandemic? The worldwide shock of the 2020 Beirut Blast has directed public attention towards the challenges of the close relationship between ports, maritime-related activities, and their cities and regions. Abundant literature already exists on port geography and port city development. Yet, the question of facilitating sustainable port expansion and city development in a limited space remains unanswered. We need more in-depth exploration of how global flows running through ports reshape the built environment. In the RePortFlows project, the definition of the 'Äòport-city-region'Äô is inspired by considering cities and regions as, constantly, dependant on and composed of complex networks, large associations, and identities, rather than fixed spatial territories marked by clear margins. Considering the current challenges, such as globalisation, climate change, migration, digitalisation, and the pandemic, I will investigate the spatial planning, transport and sustainability-related issues and questions in Rotterdam and Genoa. I will use interdisciplinary and context-specific definitions and typologies, moving beyond traditional port-city studies (WP1 Glossary and taxonomy). I will apply multi-method and data-driven approaches to map and analyse the 'Äòspaces of flows'Äô, generated by flows from the sea to the hinterland and vice versa (WP2 Atlas). I will propose tailored policy tools to integrate the transport and socio-economic potentials with the spatial and social realities (WP3 Toolbox). The outcomes of this research will be communicated and disseminated, supporting open science practices (WP4).",,2024,TECHNISCHE UNIVERSITEIT DELFT,201429.36,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2022 +P23711,101099934,Low-field 3D magnetic resonance spirometry for advanced regional exploration of respiratory diseases,"Lung function is a central concern in the fight against covid-19. Beyond the pandemic heavy losses and long-term health implications, respiratory diseases represent a major threat for the World Health Organisation. It is one of the leading causes of death worldwide, associated to our way of living and impacting all of society. Current tools for diagnosing and monitoring pulmonary conditions are hindered by poor sensitivity (lung function tests), radiation exposure (computed tomography) or examination cost (magnetic resonance imaging, MRI). They all differently fail to fully assess lung structure and function V|LF-Spiro3D aims at democratizing newly developed and breakthrough 3D MR spirometry with high performance, low-cost MRI techniques to provide a ten-minute morphofunctional MRI protocol to engage patients in a safer, easier and more comfortable way. Based on recent works at Universities Paris-Saclay and Aberdeen, in collaboration with leading MR manufacturer Siemens, SME NMR Service, major French-Dutch hospitals and patient organisations, V|LF-Spiro3D brings together multidisciplinary experts in a patient-oriented approach for both adults and children V|LF-Spiro3D will redesign current MRI architecture to perform 3D MR spirometry at low and very low field. High-performance MRI hardware will be developed with accelerated acquisitions and coupled reconstruction strategies relying on deep learning. Biomechanical lung modelling and deep data processing will be guided by implementation of 3D MR spirometry in clinical facilities to produce unprecedentedly large sets of normative and training data covering six major respiratory diseases By prioritizing both technology transfer and innovation, V|LF-Spiro3D aims to build up a one-stop-shop imaging standard for unrestricted assessment of lung pathophysiology. The impacts are expected to yield benefits beyond lung imaging and boost health deep-tech on point-of-care imaging and multi-parameter-based digital health in the EU",,2027,UNIVERSITE PARIS-SACLAY,3907276.13,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2023 +P23712,101129146,Enhancing Efficiency and Effectiveness in Education,"High-quality education is a key driver of economic growth and social progress. Despite large investments in education over the past few decades, the quality of education in some EU countries has stagnated or even deteriorated. Marginalized populations are particularly vulnerable to the negative consequences arising from inadequate educational policies. Understanding the efficiency and (cost-)effectiveness of investment in quality education is crucial for allocating resources to where they could have the largest economic and social impacts. The EFFEct research project has been established as an impact-driven initiative that aims to provide evidence-based policy recommendations to improve the quality of education. By investigating the effectiveness and efficiency of education systems and specific policies in EU countries by using (quasi-)experimental evidence, EFFEct advances knowledge in several critical areas, including diversity, equity and inclusion; teachers, trainers and digital transition; instruction and (adult-)learning. EFFEct has four interrelated objectives. Objective 1 offers novel insights on diversity, equity and inclusion by investigating targeted programs for disadvantaged students as well as religious and elite schools. Objective 2 investigates how teacher shortages can be mitigated and examines the role of digital environments. Objective 3 evaluates policies related to instruction, admission standards, and upskilling and reskilling of adults. Finally, objective 4 analyzes how the efficiency of EU educational systems has changed since the COVID-19 pandemic and establishes the main policy levers and qualitative insights that may explain efficiency changes. EFFEct brings together a multidisciplinary research team of economists, sociologists, (neuro-)psychologists, teacher trainers, education scientists, mathematicians, and sustainability and operational research experts from four European research universities, a research institute and a NGO.",,2028,KATHOLIEKE UNIVERSITEIT LEUVEN,3051008.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2024 +P23716,101061645,Mapping inequalities through the life course,"The MapIneq project studies the trends and drivers of intergenerational, educational, labour market and health inequalities over the life course during the last decades. Our main driving research questions are: 1. How do local and national opportunity structures enhance, suppress or mediate inequalities? 2. How do changes and spillovers across the life domains and over life course contribute to inequalities? 3. How are inequalities influenced by policies and societal shocks? Opportunity structures refer to social institutions, demographic and macroeconomic conditions and socio-environmental context, which we analyse across countries, regions and localities. We focus on societal changes influencing inequalities, including those related to family diversity and complexity, fertility, migration and population ageing, digitalization, the 2007-08 global financial crisis and how the covid-19 pandemic revealed and exacerbated inequalities. We compile a policy database of the educational, family, labour market, social benefits and tax-related policies, matched with subnational-level information on social and institutional structures and physical environments. This results in an easy-to-use, open access MapIneq product which consists of visualization and mapping tools, all underlying data, statistical programming tools, and open-access code. We link the information in the database to individual-level longitudinal and cross-country datasets to study the dynamic interplay between the spheres of life. This research is conducted under life-course stage specific work packages: Inequalities in the early childhood and families, Educational inequalities, Inequalities in school-to-work transitions, Unequal mid-career trajectories and Labour market exits. We consider how the covered societal changes are linked with the perceptions on inequalities across and within countries. We co-create solutions through discussion fora for stakeholder groups across multiple levels of governance.",,2025,TURUN YLIOPISTO,3206136.15,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Finland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P23722,101076414,From face-to-face to face-to-screen: Social animals interacting in a digital world,"Over millions of years, human survival has crucially depended on rapport building, seeking others'Äô social support, and sharing resources in groups. This social context has created constant evolutionary pressure to develop specific biological systems geared to interacting face-to-face with physically present others. For just a few years, we have been living in a rapidly developing digital world where interactions across society (education, friendship, health care) shift to face-to-screen interaction 'Äì strongly accelerated by the COVID-19 pandemic. How does this core change affect our social interactions? In SODI, I will contrast face-to-face with face-to-screen 'Äúlive'Äù interactions of many individuals, taking a multi-method, biopsychological approach. According to my theoretical working model, face-to-screen interactions fail to entirely engage specific, socially relevant hormonal systems (oxytocin, Œº-opioids, testosterone), which evolved to process context-dependent stimuli from face-to-face contact (mutual eye gaze, physical contact, social odour). Consequently, hormone-mediated beneficial social effects should be attenuated, while adding social stimuli should ameliorate this difference. To test my model'Äôs assumptions, I will tackle three objectives. How do face-to-screen interactions differ from face-to-face ones? Can we 'Äúsocially enrich'Äù face-to-screen interactions by adding previously lacking social stimuli? Does experimentally modulating hormone levels in the brain affect differences between face-to-face and face-to-screen interactions? In a radically innovative approach, my research combines experimental-psychological interaction paradigms, neurophysiological and subjective measures, and hormone administration to understand the merits and flaws of interacting in a digital reality. Moreover, my project aims to strike new paths for 'Äúsocially enriching'Äù face-to-screen interactions, thereby unfolding the full potential of the digital (r)evolution.",,2027,ALBERT-LUDWIGS-UNIVERSITAET FREIBURG,1604334.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P23728,101045534,Pension reforms and healthy ageing in Italy and Europe: quasi-natural experimental analysis of linked health and pension datasets,"The COVID-19 pandemic has forced many European countries to spend money that they do not have. This is creating unprecedented levels of debt and will inevitably lead to pressure for retrenchment in social welfare, with pensions seen as a key target. While some nations will seek to protect pensions, others will not. How will these pension reforms impact on healthy ageing? Will such reforms pension save money or perversely pass costs onto healthcare and other welfare systems? We propose an ambitious research programme to inform these critical questions. Our proposed research combines analysis of the Surveys on Health, Retirement and Ageing in Europe (SHARE) in 19 EU countries with specific quasi-natural experiment studies of pension reforms increasing pensionable ages (UK 1995 Pension Act and Italy 2011 Fornero Reform) and reducing pension payments (Netherlands 2013 Pension Reductions and Greece Katrougas Law 2016). Additionally the project will create innovative administrative-record linkages in Italian pension and health system data to quantify occupation-specific mortalities and unequal survival times. Overall, it builds on the PI'Äôs strong track-record in evaluating health impacts of austerity and natural experiment research designs. The anticipated findings will test critical ideas about a 'Äòhealth-promoting pension system'Äô and about which occupational groups may merit additional compensation due to lower survival times. It will help inform critical policy debates by revealing the hidden and unanticipated health consequences of pension reforms and associated inequalities.",,2027,UNIVERSITA COMMERCIALE LUIGI BOCCONI,1880430,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +P23729,101046927,Intracellular Carrier Against Resistant microOrganisms (ICARO),"Vaccines have a history of success in the control of infectious diseases. The need for new efficient vaccination strategies is of particular significance due to the emergence of new pathogens, lack of effective antivirals and the growing scenario of antibiotic resistances. Intracellular pathogens and viruses are responsible for epidemics like tuberculosis, malaria, or COVID-19. CD8+ T cells eliminate cells exposing antigens derived from intracellular pathogens via Major-Histocompatibility Complex class I (MHC-I). This antigen-presentation pathway is often subverted by viruses or intravacuolar pathogens, for which the antigenic repertoire is greatly diminished. ICARO take advantage of MEMS capabilities to obtain the proof-of-concept for a new generation of vaccines needed for diseases caused by intracellular pathogens (viruses, bacteria and protozoa) with a high societal impact. The biochips technology underlying this project has been already proven: biochips are optimal to reach and work in the intracellular environment: volume in the range of Œºm3, easy to manipulate, proven internalization by phagocytic and non-phagocytic cells and the ability to remain long period of time in the cytosol. Our vision is to develop silicon microchips that will cross the cellular barriers carrying whole inactivated pathogens to the cytosol for its presentation by MHC-I. By achieving that, ICARO might be a groundbreaking new vaccination strategy to boost CD8+ T cells responses by a rapid scouting of a full repertoire of antigens for a given inactivated pathogen. We aim to develop standardized methods for ICARO manufacturing and functionalisation to be easily applicable to other pathogens, thus accelerating the generation of new vaccines in the future",,2026,ARRAYS-FOR-CELL NANODEVICES SL,3326722.17,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Spain,,"Vaccines research, development and implementation",Vaccine design and administration,2022 +P23735,101057429,Reducing the impact of major environmental challenges on mental health,"The environMENTAL project will investigate how some of the greatest global environmental challenges, climate change, urbanisation, and psychosocial stress caused by the COVID-19-pandemic affect mental health over the lifespan. It will identify their underlying molecular mechanisms and develop preventions and early interventions. Leveraging cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large scale behavioural neuroimaging cohorts, we will identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress and substance abuse. By linking population and patient data via geo-location to spatiotemporal environmental data derived from remote sensing satellites, climate models, regional-socioeconomic data and digital health applications, our interdisciplinary team will develop a neurocognitive model of multimodal environmental signatures related to transdiagnostic symptom groups that are characterised by shared brain mechanisms. We will uncover the molecular basis underlying these mechanisms using multi-modal -omics analyses, brain organoids and virtual brain simulations, thus providing an integrated perspective for each individual across the lifespan and spectrum of functioning. The insight gained will be applied to developing risk biomarkers and stratification markers. We will then screen for pharmacological compounds targeting the molecular mechanisms discovered. We will also reduce symptom development and progression using virtual reality interventions based on the adverse environmental features - developed in close collaboration with stakeholders. Overall, this project will lead to objective biomarkers and evidence-based pharmacologic and VR-based interventions that will significantly prevent and improve outcomes of environmentally-related mental illnesses, and empower EU citizens to manage better their mental health and well-being.",,2027,CHARITE - UNIVERSITAETSMEDIZIN BERLIN,9678458.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P23742,101070819,Setting up an EU Health System Resilience testing and support programme,"COVID-19 has thrown a spotlight on the pressures on European society and on Europe'Äôs health systems. The pandemic exposed weakness in health systems'Äô abilities to prepare for and manage shock. Countries struggled in terms of resources 'Äì beds, staff, funding 'Äì and with the capacity to mobilize those resources available. Where there was the potential to innovate to meet challenges, system issues like payment mechanisms or staffing practices often made it difficult for countries to respond. This project will address how Member States can review and understand their vulnerability to future health shocks. It will also explore the steps they can take to strengthen health system resilience so that they can better prepare for different crisis scenarios and for long-term structural challenges. The project run jointly by the Observatory and OECD in close consultation with DG SANTE will develop a framework for analysing how different shocks impact on health systems functioning. It will identify the core data countries need to understand their own resilience and explain how to collect them and analyse their implications. It will develop and explain tools so that Member States can explore the contextual dimensions that are critical to responding in practice. It will then pull together all these elements and methodologies into a single Manual or Handbook that will guide countries through the process of checking their own health systems resilience against high-pressure scenarios and long-term threats. Inputs from experts including in health systems performance will help the project build on the existing work in this area and careful pilot testing in and with countries will ensure Member States can use the handbook effectively. Finally, the project will set out how the insight and evidence generated through resilience tests feeds into Member State action to become more resilient. It will set out a framework for remedial action where it is needed and strategies for implementation.",,2023,WORLD HEALTH ORGANIZATION,1106835,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Health service delivery | Health leadership and governance,2022 +P23749,101082895,Driving exCellence in Health mANaGemEnt,"Health managers are crucial to providing solutions to the current pressures and thus increasing health systems resilience and preparedness to respond to shocks. The European Health Management Association (EHMA) strives to make the voice of health managers recognised and heard at an organisational, systemic and European level, so that health management knowledge and research findings are made available and transformed into policy and practice. EHMA'Äôs strategic objectives are in line with the goals of the European Commission to improve the resilience and resource efficiency of health systems through activities such as supporting collaboration among Member States; promoting the sharing and implementation of best practices; supporting the healthcare workforce; addressing demographic challenges; and advancing the digital transformation. More specifically, EHMA's activities contribute to the general objectives of the EU4Health Programme by strengthening health systems response; strengthening resilience and sustainability; fostering international health initiatives and cooperation; reinforcing the health and care workforce; supporting innovation and the digital transformation of health systems; and supporting health promotion and disease prevention. In 2022, EHMA'Äôs aims are to communicate evidence-based practices in health management; ensure that health management supports policy-making; support health systems in exchanging good practices and implementing the lessons learnt from COVID-19; support health management capacity in Southern and Central-Eastern Europe, and; document the training needs of the health workforce to support evidence-based decision-making. These aims will be achieved through activities within six work packages, addressing the specific objectives of Article 4 points (a), (b), (c), (f), (g) and (h) of Regulation (EU) 2021/522.",,2023,EUROPEAN HEALTH MANAGEMENT ASSOCIATION,0,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Policies for public health, disease control & community resilience | Health Systems Research",Health leadership and governance | Health workforce,2022 +P23750,101082904,Driving exCellence in Health mANaGemEnt,"Health managers are crucial to providing solutions to the current pressures and thus increasing health systems resilience and preparedness to respond to shocks. The European Health Management Association (EHMA) strives to make the voice of health managers recognised and heard at an organisational, systemic and European level, so that health management knowledge and research findings are made available and transformed into policy and practice. EHMA'Äôs strategic objectives are in line with the goals of the European Commission to improve the resilience and resource efficiency of health systems through activities such as supporting collaboration among Member States; promoting the sharing and implementation of best practices; supporting the healthcare workforce; addressing demographic challenges; and advancing the digital transformation. More specifically, EHMA's activities contribute to the general objectives of the EU4Health Programme by strengthening health systems response; strengthening resilience and sustainability; fostering international health initiatives and cooperation; reinforcing the health and care workforce; supporting innovation and the digital transformation of health systems; and supporting health promotion and disease prevention. In 2022, EHMA'Äôs aims are to communicate evidence-based practices in health management; ensure that health management supports policy-making; support health systems in exchanging good practices and implementing the lessons learnt from COVID-19; support health management capacity in Southern and Central-Eastern Europe, and; document the training needs of the health workforce to support evidencebased decision-making. These aims will be achieved through activities within six work packages, addressing the specific objectives of Article 4 points (a), (b), (c), (f), (g) and (h) of Regulation (EU) 2021/522.",,2022,EUROPEAN HEALTH MANAGEMENT ASSOCIATION,173264.34,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Policies for public health, disease control & community resilience | Health Systems Research",Health leadership and governance | Health workforce,2022 +P23751,101083830,BIKRO2022 - Building a safer Internet for children in Romania with the help of new technologies,"Organizatia Salvati Copiii (Save the Children Romania) is operating the Romanian SIC since 2015, and is a member of the Inhope and Insafe networks, tackling challenges and risk exposure that the digital environment offers to children. Although interventions have been made with the purpose of providing a safer internet for children, the online is continuously changing, shifting and gaining new dangerous dimensions that threaten the integrity and online safety of children. The project aims to provide further support to children, parents, teachers and other professionals working with children in Internet Safety though information, educational resources, public awareness tools and counselling and reporting services (dedicated helpline and hotline). Updated content reflecting the new challenges brought by the COVID-19 pandemic will also be a priority for the SIC in this new project. All of these will be obtained through: 'Ä¢ SIC website www.oradenet.ro: will be redesigned, more educational resources will be made available for children and adults interacting with children, awareness campaigns will be delivered; 'Ä¢ Educational activities designed to improve children's skills to navigate safely online will be carried out for both children and adults; 'Ä¢ The existing helpline ctrl_AJUTOR: it will be redesigned and improved with a technology-based support mechanism that will ensure extra support for children in a 24/7 type of intervention; 'Ä¢ The existing hotline esc_ABUZ: it will be redesigned and improved with an automatization solution for helpline reporting mechanism that will ensure more efficient handling of potentially harmful and dangerous online content (CSAM, CSEM); 'Ä¢ Sharing information, good practices and resources with relevant stakeholders, with a focus on the National Advisory Board and the BIK Platform. Key deliverables: - 20 new or updated online resources made available, - 2500 requests handled by the helpline, - 2400 reports received by the hotline.",,2024,ORGANIZATIA SALVATI COPIII,549884.01,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Romania,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2022 +P23759,101095424,Flexible Approaches to Support Health through financing,"One of the lessons learnt from the Covid-19 pandemic is the importance of flexibility in funding and organization of health systems. European countries responded quickly to this extreme event, by expanding the amount of financial resources available for health care and reallocating financial and human resources. However, there are several other challenges for health care systems that require efficient and flexible financing mechanisms to be successfully addressed. This project undertakes a comprehensive analysis of health care financing mechanisms in Europe, by focusing on the two key stages of the process: i) budget allocation (e.g., among managing authorities, clinical areas), ii) financing of health services within a specific budget, through the definition of contracts and payment rules. We identify and examine the most prominent mechanisms underlying the relationship between the main challenges faced by health care systems (demand shocks, ageing, budget pressure) and their financing. By employing a wide range of methodological approaches, we provide evidence on the ability of existing financing mechanisms and contracts to address such challenges and study new solutions to achieve more effective, efficient and equitable health care systems.",,2026,UNIVERSITA DEGLI STUDI DI VERONA,5303782.42,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,Health Systems Research,Health financing,2023 +P23761,101100701,Health Information Safe and Cybersecured for All,"The Project HISC4ALL 'Äì Health Information Safe and Secured for All, consist of creating a FRAMEWORK involving the SME in Design a common and shared Information Security and Cybersecurity Framework for the healthcare sector, and its application process. The promoters are Instituto Nacional de Emerg√™ncia M√©dica (INEM)'ÄìPublic Institution from the Ministry of Health, responsible for the Integrated Medical Emergency System; Hospital Lus√≠adas, Private Hospital; and QUATTRO'ÄìPrivate SME, Health Sector Information Solutions Provider. Covid-19 pandemic made a sudden and urgent shifted of the patient care to citizens' homes, making the Healthcare entities more exposed to cyber-attacks. The Consortium saw the need in the market to incorporate a Information Security and Cybersecurity tool. It gives to the market a personalized service of monitoring, detection, and response to security incidents, operated by a team of specialists, based on a set of technological solutions, and supported by standards and frameworks to ensure the compliance of the service. The Consortium propose to create a new framework to assess the level of maturity of the different actors in the health sector involved in sharing data and information with and within each other. The purpose is to ensure that these exchanges take place between entities that meet certain minimum-security requirements and, to this end, comply with the highest levels of the maturity model to be developed. Outcomes will be: 1)Final Framework for Information Security and Cybersecurity; 2)Final Training, Awareness and Training program in the implementation and operation of the Framework; 3)Final Framework Application Process; 4)Framework Operation Process; 5)HISC4ALL application (proof of concept); 6)Website. The target Stakeholders are Hospital and Clinics; Institutions of the Public National Health Service; NHS); SMEs of the healthcare sector (small hospitals, clinics, dentists, pharmacies); Non-profit organizations (Firefighters).",,2024,INEM,822565.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Portugal,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P23762,101101190,Building future through an innovated and digital skilled hospital,"Throughout the most recent years, the world has been facing troubling times in what concerns health issues and crisis situations. Consequently, a growing awareness is happening so that these types of circumstances can be mitigated or avoided. The COVID-19 pandemic showed, on the one hand, how fragile the overall health systems are but, on the other hand, how resilient health professionals can be. Nevertheless, there is a clear need to give these professionals tools to stay alert and deal with situations like this one in the best way possible. As Confucius said, 'ÄúLearn as if you were not reaching your goal and as though you were scared of missing it'Äù. In this context, we believe that only a combination of a triple-front training of the health workforce (soft, ICT and hard skills) and knowledge sharing will be the beginning that leads to a better planning and management of crisis situations, patient-oriented health modules and surge capacity. Having this in mind, a European taskforce was gathered to create training modules that would facilitate further education processes for staff working in the medical sector, that includes regular strengthening and updating knowledge in medicine. Additionally, the project aims to provide training in the field of emotional resilience and digital skills that become relevant in crisis situations. It is our intention not only to boost international cooperation in health, but also to strengthen national health systems through the development of digital tools and services, digital transformation of healthcare, and improving soft and hard skills of clinical and non-clinical healthcare professionals at the European level.",,2025,INSTITUTO SUPERIOR DE ENGENHARIA DO PORTO,2525620.51,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Portugal,,Health Systems Research,Health workforce,2023 +P23791,101047214,Yeast cell factory for mRNA bioproduction,"Messenger RNA (mRNA) vaccines have become a game-changer in the fight against COVID-19, providing an exit strategy to the global crisis of our age. mRNA is now considered a promising biopharmaceutical for a vast array of medical applications. Currently, in vitro transcription (IVT) is the only available technology for mRNA production; however, it relies on a complex supply chain and costly purification process. Reliable large-scale IVT production is challenging and high production costs are an issue for low-income countries, and this will be even more critical for clinical mRNA applications requiring high doses. Yscript'Äôs groundbreaking nature lies in the generation of a specific mRNA bioproduction process in yeast, integrating innovative extraction and purification processes, representing a complete shift of paradigm compared to IVT production and a revolutionary new use of yeast. Although yeast possesses a similar mature mRNA structure as humans and is recognized as safe for pharmaceutical production, mRNA bioproduction and isolation have never been attempted. Yscript will provide groundbreaking technological improvements by: i) decreasing the mRNA production supply chain; ii) increasing the purity yield of long mRNA by avoiding premature termination occurring during IVT; and iii) guarantying mRNA stability through integrated extraction-purification processes. This will ensure the generation of high-quality mRNA therapeutics, while streamlining production and reducing costs. Yscript brings together world-class expertise in molecular biology, biophysics, biotechnology, chemistry, chemical engineering, mRNA therapeutics, yeast Ty biology, bioproduction and purification processes. The project will significantly advance the current state of the art of mRNA manufacturing. Yscript will foster citizens'Äô well-being and health, while decreasing economic and social disparities associated with biopharmaceutical-based therapies, in which mRNA is nowadays a key element.",,2025,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,3416857.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,France,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P23797,101079978,Schools4Health,"Schools4Health strives to introduce, strengthen, and sustain the adoption of a participatory whole-of-school approach to health and wellbeing. It will raise awareness amongst policy makers and build the capacities of administrators and school staff across Europe to help mainstream them. It will also invest in 'Äòbest practices'Äô that improve healthy lifestyles and health literacy and contribute to the common principles of the health promoting school (HPS) approach and other whole-of-school approaches. The consortium involves leading networks and experts in the fields of school health and health promotion. Public authorities, civil society actors and school communities in eight participating countries will work together to determine what is needed, and what can be done, also from a policy perspective, to mainstream these programmes. Schools4Health will invest directly in initiating or strengthening the overall HPS/whole school approaches in schools, through a process of exchange of policy and practice. It will invest, and directly engage approximately 16 schools across the EU in a process of selection, transfer, implementation and evaluation of best practices. These will focus on the areas of healthy food, physical activity, and mental health. All training materials, including a concise tool for policy makers and for practitioners will be included in an 'Äòonline Hub Schools for Health and Well-being'Äô. An advocacy and information campaign and other dissemination strategies will draw attention to the value of health promoting schools to resilience and recovery efforts in the face of COVID-19 and to the Hub..Schools4Health will demonstrate how HPS and other whole-school approaches to health not only put children and adolescents on a path to healthier lifestyles, but also improve educational outcomes and health literacy, and contribute to addressing inter-related societal challenges like social equity, climate change and environmental degradation.",,2025,EUROHEALTHNET ASBL,1468092.43,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Belgium,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P23811,959211,A Disruptive AntimicrobialSmart Photocatalytic Glass: A Disruptive Antimicrobial Coating for the Protection of Glass Surfaces & Designed to Tackle the Emergent Crisis of Resistant Microbes and Viruses,"Kastus¬Æ is an Award-Winning surface innovation company founded in 2014 with global headquarters and manufacturing based in Ireland. Our patented range of antimicrobial (AM) and hydrophilic coatings are designed to enhance surfaces across our 2 core Industries, Glass (TRL 8) and Ceramics. In relation to the antimicrobial coatings, the technology is designed to eliminate up to 99.99% of harmful bacteria and viruses such as Corona, C. Diff, MRSA and E. Coli. Kastus¬Æ has also been funded by Atlantic Bridge (VC) to get the technology from TRL 3 to 8 and funding is now required to get to get the glass formulation to TRL 9. Kastus¬Æ needs the EIC support to accelerate the technology into full production and allow us to expand our disruptive technology offering into the entire touchscreen and glass AM sectors. We have built the momentum and the funding and support from the EIC will enable us to expand and build a global European company with forecasted revenues in 2025 of over 'Ǩ42m. Without the funding, the risk of losing first to market advantage is high due to the large cost needed to commercialise. Previous submission to SME Instrument in July 2019, Kastus¬Æ was awarded the Seal of Excellence.",,2022,KASTUS TECHNOLOGIES LIMITED,1898815.88,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Ireland,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P23812,960713,A Whole New Category of Vehicle: The ONO Pedal Assisted Transporter,"Worldwide, e-commerce is booming and parcel delivery and urban logistics have experienced rapid growth. And in light of the current Covid-19 virus pandemic, logistics operators are struggling to cope with the enormous increase in demand as people are confined to their homes, doing their part to slow the virus. This adds to the strain on operators'Äô already present challenges such as polluting vehicles, driver shortages, being stuck in traffic jams, and the lack of flexibility in routing and costs. Yet, delivery methods have hardly evolved in the last 90 years. The time is now to rethink and transform urban logistics. At ONO, we believed that there was a need for a vehicle that would bring about change in a positive and meaningful way. So, we created a whole new category of vehicle: the ONO Pedal Assisted Transporter (PAT). It'Äôs a unique solution that is meant to improve city life quality by reducing road congestion and air pollution, all while being accessible to all genders. The ONO PAT combines the flexibility and advantages of a bicycle with the durability and cargo capacity of a van. The weather-protected electric vehicle features over 2100 litres of load volume capacity, integrated cargo loading ramps, an easy battery-swapping system, use of quality Tier-1 automotive components, and an aesthetically polished and distinctive design. Our vehicle also features the very unique selling point of having a modular platform base where one unit can be easily swapped for another module. The scope of this project includes optimising the ONO PAT, and its cargo-unit prototypes for a pre-series production, further developing the technology and software innovations, as well as optimising the business structure needed for commercialisation; preparing and setting-up for manufacturing; setting-up, testing and adjusting our service model ecosystem; testing our pre-series vehicles through fleet deployments; and conducting R&D for additional module-units and a solar roof.",,2022,ONOMOTION GMBH,2184541.08,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +P23816,101016112,"ESSENCE: Empathic platform to personally monitor, Stimulate, enrich, and aSsist Elders aNd Children in their Environment","ESSENCE aims at transforming the lessons learnt from the COVID-19 in a huge opportunity that exploits technology toward a deep evolution of the services targeting vulnerable populations: non- or pre-frail seniors, and children of the first years of primary school. To contribute to the public health response in the context of the ongoing epidemic, and preparedness for future emergencies, ESSENCE aims at boosting the creation of a new model of home-based care that relies on stimulation, remote monitoring, tele-assistance, and connection between users, families, and professionals. ESSENCE builds upon the results of MoveCare H2020 and adopts an iterative optimization process between two pillars - technology transfer of a subset of successful modules and feedback received from testing on target users 'Äì with the final target of achieving CE mark and promptly entering the mark The ESSENCE system consists of three main components: - the Community-Based Activity Center (CBAC), a holistic platform, based on virtual rooms, providing a series of diverse activities with declared recreational, socialization, educational, and assistive purposes; - the Monitoring Module, that gathers heterogeneous information from the activities mediated by the CBAC, a smart ink pen, and diverse applications to extract cognitive, physical, and emotion-related indicators. AI is exploited to provide personalized feedback, and alerts for deviations from physiological behaviors; - the ESSENCE Manager, that acts as the system control unit to manage user profiling, system configuration, possible system malfunctioning, and delivery of notifications, alerts, or feedback. Through ESSENCE, a multi-level user empowerment will be promoted both by: (i) delivering empathic feedback aimed at maximizing engagement and relieving stress; (ii) producing alerts on potential risks to family members and health and education professionals aimed at fostering early detection of possible weaknesses and anticipation of care.",,2023,POLITECNICO DI MILANO,3749351.58,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health | Innovation,,,Italy,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2020 +P23818,101027744,Dissecting the role of sex hormones in human antiviral immunity,"COVID-19 severity and mortality are consistently higher in men than women. Still, the mechanisms that underlie sex differences in human antiviral immunity remain poorly understood. Therefore, investigating sex-specific regulation of immune responses is a critical step for developing novel and effective antiviral therapies. The overarching goal of SHIFT is to dissect the precise contribution of sex hormones to human antiviral immune function by studying the immune system of individuals as they undergo sex-reassignment therapy with sex hormones. The three specific aims proposed are 1) to evaluate the sex hormone contribution to viral infection susceptibility, 2) to characterize sex hormone effects on the immune-microbe interactions and balance, and 3) to assess sex hormone effects in antiviral immune responses during infection. SHIFT will combine the experienced researcher'Äôs advanced knowledge in sex hormone regulation of immune function and metabolism, with the host lab'Äôs state-of-the-art multi-omics technologies, advanced expertise in systems immunology analysis and established collaborations in Sweden. Aims will be achieved during a planned 24-month training at Karolinska Institutet that involve technical training (sample collection and processing), analytical training (integrative computational analysis and statistics), and development of transferrable skills (project management, mentoring, leadership and communication). The two-way transfer of knowledge in SHIFT will lead to implementation of new techniques, mentoring of trainees, and identification of sex-hormone regulated pathways in antiviral immunity that will be valuable for vaccine design, antiviral therapies and immunomodulatory therapies at large. Further, the MSCA fellowship will provide a strong training path in systems immunology to lead the fellow towards academic independence in the EU and support her career goals of becoming an investigator studying immunological basis of disease susceptibility.",,2023,KAROLINSKA INSTITUTET,232140.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Gender,,,Sweden,,Clinical characterisation and management,Disease pathogenesis,2021 +P23821,101137157,enhanced manufacturing of broadly potent equine polyclonal¬†Fab¬†with a¬†Rational Immunization strategy against¬†Coronaviruses,"e-FabRIC will develop a new hyperimmunization strategy for generating high titers equine immunoglobulins having a broad neutralizing specificity against viral targets belonging to same subfamily phylogenic tree. The viral subfamily selected to demonstrate the unique benefits of this innovative way to induce highly anti-viral active antibodies is the sarbecovirus subfamily. The equine antibodies will be processed as purified F(ab'Äô)2 fragments, a well-known pharmaceutical product with a strong historical safety record in human patients. The F(ab'Äô)2 antibody fragments generated by e-FabRIC are expected to display a unique and very wide neutralizing activity spectrum. This new property will be the synergistic outcome of the immunization with a nanoparticle co-displaying 8 different sarbecovirus RBD subunits (designated as 'Äúmosaic antigen'Äù) and the natural immunogenetic diversity present in individual horses. In each individual horse, the mosaic antigen immunization will drive the generation and maturation of antibodies highly focused on conserved epitope structures shared by the different sarbecovirus RBD subunits and associated with viral neutralization. As each horse's own immunogenetics will mature the mosaic antigen-specific antibodies in a different way, several equine individual antibody specificities will be pooled in order to expand the overall broad viral neutralizing activity of the final pharmaceutical product. The combined multiplicity of individual antibody response diversities and the highly focused antibody responses induced by the mosaic antigen will be the basis of a broadly potent, immunotherapy pharmaceutical F(ab'Äô)2-based product able to significantly reduce the clinical and societal impact of any emergence of a new human sarbecovirus outbreak. The scientific and technical learnings of this new and powerful immunization strategy will be applicable to other viral families from which human infectious threats may arise.",,2026,FABENTECH,8356538.41,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies,2023 +P23822,101058094,Pro-active Pandemic Crisis Ethics and Integrity Framework,"The overall goal of the PREPARED project is to develop an operational ethics and integrity framework, which safeguards key ethical values, supports a rapid and effective research response to crises and improves overall pandemic preparedness. European Commission president Ursula von der Leyen outlined plans to cope with ""an era of pandemics"" by developing ""Europe-wide fast-reaction system designed to respond more quickly to emerging medical threats"". Fast reaction systems, including accelerated research, are likely to face significant ethics and integrity challenges. The PREPARED project will create an international network of research funders (private and public), researchers, policy makers, publishers and citizens (a) to identify, analyse and validate the emergent research ethics and integrity challenges in the context of sudden, unexpected and global crisis, (b) to facilitate bottom-up, solution-focused, participatory dialogue, (c) to develop a values-based framework for research ethics and integrity in a global crisis which supports rapid and effective decision-making whilst maintaining scientific reliability and avoiding short-cuts in the protection of research participants, (d) to propose policy options at the EU level and tailored support for relevant stakeholders in the form of operational guidelines and short complements to existing codes and (e) to achieve influential strategic engagement through high-level synergy building and the provision of engaging training material to ensure uptake of the project's outputs so as to improve overall preparedness for global crises. Given that this is a Coordination and Support Action, the high-level consortium consists to 35% of research institutions (given that this is a CSA) and to 65% of organisations which can significantly contribute to and then leverage results (e.g. WHO, UNESCO, EDCTP).",,2025,UCLAN CYPRUS LIMITED,4201759,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Cyprus,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues in Governance,2022 +P23825,101055416,Multivalent Supramolecular Nanosystems as Dynamic Virus Blockers,"Background: Viral pandemics pose great risks to current and future human health and global trade. Newly emerging viruses can display a broad variety of shapes, such as spherical or filamentous, and spike proteins have different lengths and densities, as seen in coronaviruses and influenza viruses. Viruses can mutate rapidly under evolutionary pressure, resulting in changes to antigen epitopes and reduced efficacy of drugs and vaccines. These variances between viruses and across mutations present challenges to broad-based anti-infection intervention and vaccination. However, the initial docking of viruses to cell surface receptors via heparan sulfate or polysialic acids are common for a number of viruses, offering an attractive target for wide-reaching intervention. Aim: The SupraVir project will provide a new concept for multivalent supramolecular assemblies as self-adaptive universal virus blockers. This new type of virus inhibitor can adapt to different virus morphologies and mutations by dynamic self-assembly of its virus binding sites. The inhibitor will use a combination of different receptors and bind a great majority of all known viruses by mimicking generic host cell surface receptors. Methodology: My approach will use self-assembled surface-active supramolecules that mimic the host cell surface efficiently and dynamically. With this method I will avoid a bulk phase that does not contribute to the activity, thus reducing potential toxicity. At the same time, the amphiphilic building blocks can interfere with the viral envelope or capsid and permanently inactivate the virus. Impact: SupraVir addresses the central question: What might prevention of viral infections look like in 2030? I contend that there is a new option, based on mimicking dynamic cell surface receptors with multivalent supramolecular nanosystems that can self-adapt to inactivate rapidly mutating viruses.",,2027,AW TECHNOLOGIES IVS,2763663.86,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Denmark,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P23830,101003595,"Exploration of safety, tolerability and clinical efficacy of Solnatide IMP in patients infected with the 2019 new coronavirus","Clinical features of patients infected with the 2019-nCoV have revealed that these patients suffer from severe respiratory failure, and presence of a life-threatening pulmonary oedema (PPO). Approx. 30% of 2019-nCoV-patients further develop life-threatening Acute Respiratory Distress Syndrome (ARDS). Mortality rate of these patients is very high. Initiator and Scientific Coordinator of the project, APEPTICO, is a SME biotechnology company (EMEA/SME/012/09) developing peptide-based products targeting life-threatening pulmonary diseases, including oedematous respiratory failure, acute lung injury, primary graft dysfunction, high altitude pulmonary oedema and PHA type 1. APEPTICO'Äôs lead-compound Solnatide (INN) has been designed for the therapeutic treatment of patients with Acute Respiratory Distress Syndrome (ARDS) and various forms of life-threatening Pulmonary Oedema (PPO). Orally inhaled Solnatide has delivered clinical proof-of-concept in one Phase I, and in two Phase II clinical studies (EUDRACT No. 2011-000223-33, 2012-001863-64, 2013-000716-21). Today, no medicine has been approved for the therapeutic treatment of Pulmonary Permeability Oedema and ARDS. Currently, Solnatide is subject to a Phase IIB trial (EUDRACT No. 2017-003855-47) for the 'Äútreatment of pulmonary permeability oedema in patients with ARDS'Äù. The Phase IIB clinical trial has been approved by the German and the Austrian Competent Authorities, as well by Ethic Committees of leading Medical University Hospitals in Germany as well Austria. Most recently, APEPTICO has entered into a partnership with HAISCO Pharmaceutical Group in Chengdu, Sichuan, P.R. China. HAISCO has access to core areas and leading Medical University Hospitals in the P.R. China. Accordingly, APEPTICO proposes to immediately apply the Solnatide IMP for the treatment of patients infected with the 2019-nCoV and to demonstrate safety, tolerability and clinical efficacy of Solnatide IMP in 2019-nCoV patients. The overall project coordination and external communications is by RTDS Association (www.rtds-group.com/association)",,2022,"RTDS - VEREIN ZUR FORDERUNG DER KOMMUNIKATION UND VERMITTLUNG VON FORSCHUNG, TECHNOLOGIE UND INNOVATION (RTDS VEREIN, ENGL. RTDS ASSOCIATION)",1772367.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Austria,,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Clinical trials for disease management | Phase 2 clinical trial",2020 +P23831,101003688,"Epidemic intelligence to minimize 2019-nCoV'Äôs public health, economic and social impact in Europe","EpiPose aims to provide urgently needed answers about the epidemiological characteristics of 2019-nCoV, the social dynamics of the outbreak, and the related public health preparedness and response to the ongoing epidemic, as well as to assess its economic impact. The consortium consists of 6 partners in 5 countries (BE, NL, UK, CH, IT) who provide complementary expertise in mathematical and statistical modelling of infectious diseases, participatory surveillance systems, living systematic reviews, and health economic analysis and have a strong international public health network. EpiPose aims at a quick delivery of results, according to the following objectives: (1) To collect and share epidemiological data of 2019-nCoV as widely as possible (2) To provide country-specific estimates of key epidemiological parameters (3) To model the expect impact of 2019-nCoV on morbidity and mortality (4) To monitor awareness and behavioural change during the 2019-nCoV epidemic (5) To provide health economic analyses for interventions within the EU (6) To foster the interaction between the scientific community, public health agencies and the public EpiPose aims to make all research data, code, tools and results publicly available and its dissemination plan targets active communication and interaction with policy makers, other scientific groups and the general public. As such, the epidemic intelligence provided by EpiPose will help minimize the 2019-nCoV'Äôs public health, economic and social impact.",,2023,UNIVERSITEIT HASSELT,5048714.01,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Belgium,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Approaches to public health interventions | Policy research and interventions | Systemic/environmental components of capacity strengthening,2020 +P23832,101137229,Developing broad-spectrum antiviral drugs for pandemic preparedness,"Antiviral drugs will be key in the management of future virus outbreaks. For each virus family with epidemic/pandemic potential, stockpiles of potent drugs are needed that can be deployed when a new pathogen emerges. Such broader-acting drugs (targeting conserved viral functions) are needed as of 'Äúday one'Äù of an outbreak, for treatment and prophylaxis (e.g., in HCW and frail patients). In combination with quarantine measures, such drugs will delay (global) spread, allowing time for vaccine-development. Since the 2003 SARS outbreak, PANVIPREP'Äôs core partners have successfully collaborated in leading European antiviral drug research projects. This provides a solid scientific basis in combination with translational drug discovery expertise. The team includes virologists, biochemists, structural biologists, medicinal chemists and pharmacokinetics experts. Previously developed know-how and toolboxes will be a major asset to achieve immediate impact. PANVIPREP aims to greatly expand the antiviral portfolio and identify novel druggable targets of high-risk RNA viruses. Hits will be identified through (i) phenotypic antiviral screening of compound libraries (ii) structure-based drug design, (iii) in silico screening, supported by the latest machine-learning methods. We will deliver 25 to 50 high-quality, broad(er)-spectrum (pan-genus/pan-family) hit molecules/hit series. Two of these will be developed to the early lead stage, including proof of concept in animal infection models. Remaining hits will serve as chemical tool-compounds to explore mechanisms of action thereby identifying novel druggable targets in RNA virus replication. This in turn will accelerate target-based drug design efforts. The workflow will integrate best practices in antiviral drug discovery with a range of methodological innovations, including AI-based methods, thus renovating and accelerating the antiviral hit discovery pipeline future use and contributing to pandemic preparedness.",,2027,ACADEMISCH ZIEKENHUIS LEIDEN,8799224.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Netherlands,,"Therapeutics research, development and implementation",Pre-clinical studies,2024 +P23833,101137192,Antiviral Therapeutics for Rapid Response Against Pandemic Infectious Diseases,"The European Consortium ""Antiviral Therapeutics for Rapid Response Against Pandemic Infectious Diseases"" (AVITHRAPID) aims to support the search for novel broad-spectrum antiviral compounds by advancing multiple approaches. Building on a pre-existing set of bioactive small molecules, which are at least at the validated hit level, AVITHRAPID strives for the development of pre-clinical candidates targeting several viruses. This will be achieved by combining the relevant expertise for pre-clinical drug discovery, including molecular modeling, biochemical and cell-based assays, X-ray crystallography, medicinal chemistry, biophysical binding studies, ADMETox profiling, in vitro and in vivo PK, as well as animal disease models. In addition, the consortium aims to conduct a Phase 2a clinical trial for a small molecule developed against Zika virus. Moreover, the consortium aims to identify and validate further viral targets and thereby contribute to the search for novel antiviral targets. As a consequence of the activities in AVITHRAPID, an early-stage drug discovery pipeline will be established that can be used to rapidly identify and develop novel antiviral compounds against emerging diseases.",,2028,FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV,8205179.4,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Flaviviridae | Novel Pathogen,,,,,,,,,Zika virus disease | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2024 +P23835,101137459,Deconstructing the protective immunity of yellow fever virus 17D to inform flavivirus vaccine design,"While endemic to the tropics, flaviviruses like Zika, dengue, West Nile or yellow fever virus are re-emerging pathogens of global health concern. Climate change and urbanization have largely contributed to the dissemination of their mosquito vector and Europe has in recent years been regularly confronted with autochthonous cases. Few vaccines are licensed to prevent flavivirus disease, but the yellow fever 17D (YF17D) vaccine has a unique track record of efficiency and safety. Intriguingly, despite its success, how YF17D induces immunity remains poorly understood. The YELLOW4FLAVI consortium aims to fill the gaps in our understanding of the mechanism of action of this vaccine by linking the structure of the viral particle to the resulting host immune response, in order to learn about optimal vaccine design for flaviviruses in general. Since social acceptance of vaccines is critical for their success, we will also develop optimal communication methods. This will provide us with the tools to tailor vaccine design not only to achieve optimal immune protection, but also to facilitate actual implementation.We are molecular and structural virologists, cell biologists, immunologists, computational scientists, clinicians, and social scientists assembled in a tight collaborative network. To pursue our goal of obtaining a blueprint for determinants of long-lasting immunity for flavivirus vaccine candidates, we will use cutting-edge technologies like cryo-EM, super resolution microscopy, spatial transcriptomics, high-dimensional spectral flow cytometry, single-cell RNA sequencing, advanced cell engineering, small animal models, and clinical studies. In a unique manner, the consortium thereby follows a thread of events from the early response at the site of vaccine injection to the population perception of vaccination, harnessing an enhanced understanding of one of the most successful vaccines of mankind for the development of novel lines of defense against new and old threats.",,2029,INSTITUT PASTEUR,17334304.88,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Flaviviridae,,,,,,,,,Other,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine design and administration | Characterisation of vaccine-induced immunity | Approaches to public health interventions | Communication,2024 +P23836,101132974,One Health Surveillance and Vector Monitoring for cross-border pathogens,"Within OH SURVector, 8 institutions from the 5 countries Austria, Czech Republic, Greece, Hungary and Slovak Republic team up to setting and scaling up One Health Surveillance targeted to vectors and vector-borne diseases. The Consortium builds up on experts from the different sectors Public Health and Veterinary Public Health, environmental health and biology, epidemiology, from institutions with different roles within their country, including the competent authority, national agencies, National Reference Laboratories and academia. Within this Consortium we have decades of experience in the translating surveillance outcomes into policy and communicating health topics to different audiences. The overall aim is to protect the health of humans, animals and the environment by a) the early detection of changes related to vector and/or pathogen presence in Consortium Member States, b) the early epidemic detection and monitoring of ongoing outbreaks of vector-borne diseases, and last but not least c) strengthening the cross-sectoral collaboration on national and cross-border level towards an integrated One Health approach. The specific objectives of OH SURVector are as manifold as the specific needs, capacities, climatic conditions and specific national contexts of the Consortium Member States. In the focus of this project will be the two vector groups ticks and mosquitoes and following pathogens: Borrelia spp., tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus and West-Nil virus. Activities within OH SURVector include extensive field work to sample vectors, species determination and pathogen screening of vector samples, capacity building within labs and between Consortium Member States, preparing national data structures for efficient management and sharing of vector data, and turning health data into One Health by efficient communication and dissemination.",,2026,AGES - OSTERREICHISCHE AGENTUR FUR GESUNDHEIT UND ERNAHRUNGSSICHERHEIT GMBH,8470308,Disease Vectors | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Other,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Austria,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies | Disease surveillance & mapping,2024 +P23838,101086257,a research and InNOvation Partnership for enhancing the surveillance and control of mosquito VECtors of emerging arboviruses,"Over the past 10 years, arboviral diseases, such as dengue, Zika, chikungunya and yellow fever, have (re)emerged with increasing prevalence and severity. Although these arboviral diseases are more prevalent in tropical countries, increasing numbers of autochthonous cases are being reported from European countries; hence raising concerns about the potential for the establishment of these pathogens in temperate regions. In the absence of effective vaccines and treatments, preventing these diseases at the global scale continues to depend largely on controlling mosquito vector populations, interrupting human'Äìvector contact or both. Unfortunately, the recent resurgence of Aedes transmitted arboviral diseases worldwide highlights the limitations of current vector control to prevent epidemics and to reduce the incidence of diseases. New, affordable, scalable and community-based vector control measures are urgently needed to prevent the introduction, spread and establishment of Aedes-borne diseases in Europe and beyond. The INOVEC project proposes to build a large pan-European, cross-sectoral and multidisciplinary network to develop, optimise and promote integrated approaches and innovative tools for the surveillance and control of mosquito vectors of emerging arboviruses. INOVEC will gather 21 academic and non-academic institutions specialized in vector biology, social sciences and product development to stimulate basic and applied research, strengthen capacities, promote career development and facilitate knowledge and technology transfer to countries at increasing risk of arboviral diseases. INOVEC has the commitment to coordinate and integrate sectors in order to maximise impact, raise awareness of policy makers and stakeholders, and participate in the improvement of innovation potential at the European and global level. INOVEC will contribute to international efforts to improve global health and human well-being by reducing the burden of vector borne diseases.",,2026,INSTITUT DE RECHERCHE POUR LE DEVELOPPEMENT,1506132,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Bunyaviridae | Flaviviridae | Unspecified,,,,,,,,,Disease X | Other,European Commission,Europe,Europe,Europe,Unspecified,,,,France,,,,2023 +P23840,101086640,Eco-Epidemiological Intelligence for early Warning and response to mosquito-borne disease risk in Endemic and Emergence settings,"Mosquito-borne diseases place a heavy burden on society, causing widespread suffering and driving poverty. They are increasing in prevalence, geographical distribution and severity, representing a growing threat worldwide. Hence, there is a need for better disease intelligence, capable of anticipating and identifying eco-epidemiological risks leading to explosive epidemics and emergence in previously unaffected areas. The basis of such intelligence stems from a deep understanding of the factors that drive disease circulation, emergence and spread. This requires insights into the complex interplay between humans, pathogen-carrying mosquitoes, pathogen reservoirs (e.g. birds), and a changing environment. The E4Warning consortium brings together interdisciplinary, innovative, and open science to contribute to the One Health paradigm shift that is required to tackle the spread and transmission of zoonotic deadly pathogens, and harness this shift to nowcast and forecast mosquito-borne disease risk in a constantly changing and globally connected environment. Our work aims to disrupt disease transmission pathways connecting humans, mosquitoes, and birds through innovative eco-epidemiological modelling tools and intelligent digital solutions, co-designed and implemented by public health administrations. Open innovation strategies and big data tools are the cornerstone of the next-level One Health Early Warning Systems required in the face of mounting mosquito-borne disease threats.",,2026,AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS,4368306.03,Human Populations | Disease Vectors,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Other,European Commission,Europe,Europe,Europe,Unspecified,,,,Spain,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Vector biology | Disease transmission dynamics | Disease surveillance & mapping | Approaches to public health interventions,2023 +P23841,101080238,"Boosting Societal Adaptation and Mental Health in a Rapidly Digitalizing, Post-Pandemic Europe","BACKGROUND: Adolescents are at particularly high risk for digital technology overuse, including in response to the COVID pandemic, and are therefore vulnerable for its potential harmful effects on mental health. Problematic usage of the internet (PUI) is thought to represent a marker of disrupted self-management, with major consequences for individual and societal health and wellbeing. AIM: Bootstrap brings together a multidisciplinary consortium aiming to initiate health and social policy and practice change designed to reduce the harmful effects of digitalization on mental health, particularly for young people. APPROACH: We will co-create a digital screening and assessment platform to understand which individuals are at-risk for developing PUI. Algorithm-based models will be used to predict which individual will benefit from which type of self-management intervention, and these preventative behavioral interventions will be tested for their (cost)effectiveness. Finally, we will develop a policy toolkit in co-design with stakeholders, to promote human digital rights accountability at the local, national, and European level. IMPACT: Bootstrap will provide unprecedented scientific knowledge on the psychological mechanisms underlying (risk for) PUI and potential interventions. Improved self-management and tools to optimize healthy internet usage will promote mental health and prevent mental ill health in adolescents, and contribute to reducing stigma. In addition, our policy toolkit will empower policy makers and private companies to (self)regulate with the intent to protect vulnerable groups. In the long run, Bootstrap will thus contribute to improving mental wellbeing across Europe and beyond.",,2028,INSTITUT CATALA DE LA SALUT,5904072.2,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Digital Health,,,Spain,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2023 +P23847,101061729,REshaping Supply CHAins for Positive social impact,"The aims of this proposal are: 'Ä¢ To analyse social, economic and environmental changes and disruptions (including covid) and evaluate their impact on SCs, identifying related challenges in terms of relationship between countries, configuration of the network, impact on employment. 'Ä¢ To study and propose a set of SC models for the evolution of global SC integrating strategies like resource efficient, closed-loop and humanitarian as a way to increase EU resilience and sustainability. Particular attention will be given to the role of digitalization as a way to establish new paths for social inclusion taking into consideration the needs of urban and rural areas. Some important European sectors like fashion, automotive, medical and machine tools will be analysed with case studies and survey. 'Ä¢ To develop Innovative tools for monitoring and assessing sectoral trade patterns and defining mechanisms to evaluate relationship of disruptions like pandemic and global value chains taking into consideration impact on employment, economic growth, incomes etc also in the long term. Moreover, it will be analysed the impact of different trade patterns, on the EU value added of sectoral and countries with a specific focus on analyzing income inequalities and proposition of decent work and social cohesion. Particular attention will be gives to gender issues and social disparities. 'Ä¢ To develop innovative policy scenarios with recommendations for future global value chains: policy scenarios will be based on Key horizontal issues impacting on several sectors and will provide recommendations for EU, national and sectoral strategies, policy measures and targeted actions aimed at shaping fair, inclusive and sustainable trade patterns, value and supply chains as well as production networks.",,2025,CONSIGLIO NAZIONALE DELLE RICERCHE,2192850.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Italy,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2022 +P23848,101081266,"The Greek Safer Internet Center SaferInternet4Kids.gr: Awareness, Helpline, Hotline","SI4Kids2 aims to continue uninterrupted and enhance the successful operation of the Greek Safer Internet Center SaferInternet4Kids (Greek SIC) offering an Awareness Center, a Helpline and a Hotline. The Greek SIC operates since 2016 providing a dynamic awareness axis that contributes towards a safer digital space where the rights of children and all digital citizens are safeguarded. The Helpline, which operates since 2012, will expand its scope to address issues emerging from the COVID19 pandemic. The SafeLine Hotline, which operates since 2003 as a member of INHOPE, will expand its monitoring and N&T procedures and will explore the possibility to process CSEM reports. The Greek SIC will contribute to the activities of the Insafe/INHOPE networks, and will further expand its stakeholder network aiming to promote national policies. Moreover, it will engage into its activities a dynamic youth panel that will assist to identify emerging trends and to raise awareness among peers. SI4Kids2 will address spherically all objectives of the Call text and the Digital Europe Programme implementing the following three axis thus covering the entire spectrum of internet safety in Greece. The Greek SIC will: - lead the digital transformation through its awareness axis, aiming to support and educate a variety of target groups, primarily children so that they become responsible digital citizens, but also educators of all levels, parents, grandparents, caretakers and all professionals working with children. - expand the national Helpline (www.help-line.gr), which operates a telephone and chat service, and is a point of reference for all queries related to internet safety issues and the use and misuse of digital technology. - augment the activity of SafeLine (www.safeline.gr), the Internet Hotline for illegal internet content which places emphasis and absolute priority to the efficient processing of CSAM reports, and constitutes the most long-lasting action of the Center.",,2024,IDRYMA TECHNOLOGIAS KAI EREVNAS,423463.2,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Greece,,"Secondary impacts of disease, response & control measures",,2022 +P23855,101106986,Meta Analyses of Heterogeneous Omics Data,"Meta Analyses of Heterogeneous Omics Data (MAHOD) will establish a framework in which data available in online repositories from previously performed Omics studies (i.e. metabolomics for analyses of small molecule metabolites in biofluids, proteomics for similar studies of proteins, etc.) will be analysed simultaneously using highly interpretable machine learning tools. These tools will reconcile differences in experimental design, demographic compositions, and modality (samples and variables that are not directly comparable). The ultimate goal of this research will be enable new insight into disease states and measure the statistical power based on the wealth of information and replicate samples available online. This will information will be exploitable by researchers in academia and industry, and will benefit the European Research Community by making better use of the data currently available for critical projects, and enable new research directions into diseases that are either poorly treatable or understood. The framework will be evaluated by an analysis of existing data on a rare disease (narcolepsy), and a much more common disease (long COVID) to ensure that the technology scales from a relatively low volume of information, to a much more challenging ""big data"" problem. This proposal will be carried out by an experienced researcher (ER) who completed their PhD in chemometrics, or the application of multivariate statistics and machine learning to chemical data. The ER is in a relatively unique position to bridge the gap between their knowledge of information and computer science, and domain knowledge related to the instrumentation required to perform Omics studies. The ER will be supervised by a computer scientist, who is an expert in the field of multivariate analysis and algorithm design.",,2026,UNIVERSIDAD DE GRANADA,197456.77,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Spain,,Clinical characterisation and management,Disease pathogenesis,2024 +P23856,101042908,"The Old, the Young, and the Uncertain Future: Using High-Dimensional Stochastic Overlapping-Generations Models to Evaluate Fiscal Policies that Shift Risk and Resources Across Generations","Policy decisions about government borrowing, taxation, and spending have a differential impact on generations and thus imply substantial intergenerational transfers. The costs and benefits of these policies occur over decades and come with large uncertainty, for instance related to productivity growth, global financial conditions, and demographic trends. Therefore, fiscal policies, whether intentional or not, transfer risk and resources across generations. Assessing their impact on welfare calls for simulating such policies in models that include the relevant demographics and risks, yet also the related risk-premia. The latter lower government borrowing costs relative to the expected return on investments and are thus particularly important for the welfare implications of fiscal policy. SOLG for Policy aims to build stochastic overlapping-generations (SOLG) models that integrate all these elements and are thus able to quantitatively assess the welfare implications of fiscal policy choices involving intergenerational redistribution and risk-sharing. To solve these models despite their high-dimensional nature, SOLG for Policy leverages recent advances in computational economics based on adaptive sparse grids (ASGs) and develops three extensions of this approach. First, using shape-preserving ASGs to facilitate value function iteration. Second, merging ASGs with endogenous grids to avoid compute-intensive optimization steps. Third, parameterizing intergenerational distributions to further alleviate the curse of dimensionality. Policy questions that will be addressed include: Should the debt accumulated in the Covid crisis be paid down through taxation or do low real interest rates make it desirable to leave the debt and its uncertain burden for future taxpayers to deal with? Is it feasible and desirable to make the pension system provide less redistribution yet more insurance across generations, and how can this be achieved?",,2027,KARLSRUHER INSTITUT FUER TECHNOLOGIE,1439129.83,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P23874,101138690,Novel ApameR-Based Rapid Test Technology for Virus Detection,"Rapid care tests and patient-oriented bedsite testing, termed as point of care (POC) testing, have proven unanticipated relevance for the fast detection and containment of the pathogen in the course of the corona pandemic. We have developed RNA aptamer based sensors as a basis for a novel rapid care test. The sensor will give a florescent signal once the target molecule attaches to its aptameric site. The sensor as the main component of a novel POC test will be produced by a cheap and scalable biotechnological synthesis. The unique selling points of our invention are the cheap and scalable production of the sensor molecule and the high flexibility in terms of analytes that can be covered by aptamers. To proof our concept and to demonstrate the applicability of our aptamer sensors we will choose the avian influenza virus as an use case, based on the high relevance of this disease in veterinary medicine and its perception as a high risk disease for the next human pandemic. Our test will comply with the ASSURED criteria of the WHO: affordability, sensitivity, specificity, user friendliness, rapid and robust, equipment-free and deliverable to end-users Our aim is to establish a RNA aptamer based sensor as a basis for a cheap single-use test according to the ASSURED criteria. In this action, we will establish the applicability of our highly sensitive and selective RNA based sensor. We will devolop a prototype of a POC test and test the novel sensor principle under laboratory and environmental conditions. In addition, we will analyse the market and patent situation and the stepstones to be taken for an approval by the European authorities. We will finally establish our own IPR position as a basis for the further road-to-the-market.",,2025,DWI LEIBNIZ-INSTITUT FUR INTERAKTIVE MATERIALIEN EV,159000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Novel Pathogen,Other,,,,,,,,Pandemic-prone influenza | Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P23875,874735,Versatile Emerging infectious disease Observatory,"Our vision is to establish a Versatile forecasting, nowcasting, and tracking system (VEO) serving as an interactive observatory for the generation and distribution of high quality actionable information for evidence-based early warning, risk assessment and monitoring of Emerging Infectious Diseases and Antimicrobial resistance by public health actors and researchers in the One-Health domain.VEO will be built by an iterative process between data science and technology experts, disease experts from public health and academia, social scientists, and citizen scientists. The VEO data platform will support mining, sharing, integration, presentation and analysis of traditional and novel 'ÄòBio data'Äô with a range of 'ÄúContextual data'Äù, integrating publicly available and confidential data. The VEO analytical platform will support data-intensive interdisciplinary collaboration of geographically distributed international teams, co-creation of novel advanced analytical solutions, and involving citizen scientists through crowdsourcing of specific challenges. In addition, we will develop workflows to integrate high density laboratory data (genomics, phenotyping, immunomics) into the VEO system and into risk assessments. The VEO system is (co)designed and tested through five complementary use case scenarios, reflecting main pathways of disease emergence, to attune developments to the needs of its intended users, and obtain proof-of-principle of utility, including ethical, legal and social implications.",,2024,ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM,20292592.32,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen | Unspecified,,,,,,,,,Disease X | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,,,2020 +P23878,101136531,COordination MEchanism for Cohorts and Trials,"The overall goal of COMECT is to coordinate activities across Europe'Äôs strategic adaptive platform trials (APTs) and cohort studies (CS) on infectious diseases (IDs) with epidemic or pandemic potential, by overseeing and facilitating dialogue, sharing of good practices, promoting collaboration and coordination across studies and providing updated information on initiatives and innovation in ID clinical research. COMECT will build on and strengthen existing networks and infrastructure. These include EU-funded coordination mechanisms and networks, namely the Trial Coordination Board (TCB), Joint Access Advisory Mechanism (JAAM), the Cohort Coordination Board (CCB), and the ECRAID Coordinating Comittee. COMECT will develop a visible, well-defined coordination mechanism to highlight Europe's capacity and competence as an attractive base for clinical research. COMECT will deliver: 1) an expanded, combined European coordination mechanism that will work on harmonizing research initiatives, exchange of good practices, and stakeholder engagement across ID clinical studies in outbreaks and during inter-epidemic phases. 2) a strengthened JAAM to support coordination through independent scientific assessment of compounds/vaccines and recommendations for APTs to evaluate the new compound in new or adapted platform trials. 3) the mapping of stakeholders and their respective activities relevant to APTs and CS 4) a harmonised approach cross-study identification, assessment, and reuse of participant-level data from European APTs and CS 5) coherent communications and stakeholder engagement across all activities 6) a sustainability plan for the continuation of activities beyond the funding period. COMECT will quickly adapt coordination efforts to a changing research landscape and to new ID threats. COMECT will operate in close collaboration with other emergency preparedness mechanisms, such as HERA, EMA, GLOPiD-R and the European Pandemic Preparedness Partnership.",,2026,FOLKEHELSEINSTITUTTET,3270000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Norway,,"Policies for public health, disease control & community resilience",Community engagement,2023 +P23879,101102733,Delivering a Unified Research Alliance of Biomedical and public health Laboratories against Epidemics,"Outbreaks of infectious diseases are increasing due to multiple local and global interaction changes disrupting the fragile balance of the complex human-animal-environment ecosystem. The increased frequency and complexity of health threats require a different, unified form of preparedness and a coordinated, fast, reliable and effective emergency response. DURABLE is a tailored solution to this recognised need - a strong network of world-class basic and translational research institutes and public health centres across Europe with an outstanding track record in public health support with global reach. DURABLE aims to provide high-quality scientific information in record time to support HERA's decision-making in preparing for and responding to cross-border health threats and assessing the impact of countermeasures. DURABLE will coordinate a global collaboration, from pathogen detection, evolutionary analysis and threat characterisation, with One Health approach, to data and information collection and sharing, for optimal threat response. DURABLE is a unique multidisciplinary consortium with complementary expertise to meet this challenge and build productive interactions with HERA and other stakeholders. Due to their outstanding track record and experience in the field, the DURABLE consortium is competent from day one. DURABLE will develop and validate a roadmap for rapid deployment of key countermeasures, test the robustness of the network, and assess key aspects of its emergency mode when simulating or dealing with identified threats. Additionally, DURABLE will focus on long-term sustainability by focusing on capacity building, training the next generation of researchers and developing pandemic preparedness training modules for the network and beyond. Ultimately, DURABLE will be a one-stop shop for diagnostics, research, preparedness and response to current and future health threats for the benefit of citizens in the EU and worldwide.",,2027,INSTITUT PASTEUR,27217623.73,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,France,,,,2023 +P23880,101103299,Clinical Trials Community Africa Network,"With over 25% of the global disease burden, only 3% of global clinical trials occur in Africa. This disproportion is driven by inadequacies in clinical research capacity, regulatory process ambiguity, deficient regional patient and disease area data, and lack of visibility of existing clinical research capabilities in Africa. To address this disproportion, this proposal seeks to establish the Clinical Trials Community Africa Network (CTCAN), a collaborative framework of key clinical research stakeholders in the African region, pharma partners, and other relevant international stakeholders, with the overarching goal of bringing more clinical trials to the region in a sustainable and coordinated manner. This collaboration will map and draw on the experience and expertise of already existing networks and initiatives. It will create a network of subnetworks that will foster coordination in clinical research, by ensuring and encouraging alignment in disease area prioritization, raising awareness and visibility of existing capacity from sites and labs across Africa, operationalising the regulatory processes across the region, and strengthen less experienced sites and labs through a clinical trial preparedness framework, while encouraging inter- and cross-continental knowledge and expertise sharing. CTCAN will use and expand the Clinical Trials Community (CTC) platform, an electronic platform consolidating data on researchers, regulations, sites, and epidemiology across the continent. The result will be an ever-present and ready-to-go pool of clinical research sites and labs with the agility to rapidly address new and emerging global health threats, epidemics, and pandemics, thereby efficiently contributing towards clinical research in pandemic preparedness. CTCAN will lay the foundation for a sustainable network of clinical trial sites and laboratories in sub-Saharan Africa by leveraging and initiating collaboration between existing sub-networks, funders, and pharma.",,2025,NUVOTEQ (PTY) LTD,1271009.3,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Africa,Unspecified,,,,South Africa,,,,2023 +P23882,101103174,Pan-Africa network for genomic surveillance of poverty related diseases and emerging pathogens,"The main aim of the proposed project is to use genomic epidemiology of tuberculosis, malaria and emerging and re-emerging pathogens in Africa as to better understand disease etiology, dynamics of disease transmission, and evolution of drug-resistant pathogens. The study also aims to increase Africa's capacity in bioinformatics, genomics, genomics data management, biobanking, and promote data sharing. Our goal is to improve the health of Africans with innovations in disease surveillance, equip the next generation of African scientists with cutting edge skills and strengthening south-south research collaborations. We propose the following hypotheses: 1. Increased capacity in genomic epidemiology will enable more effective disease surveillance in Africa. 2. Increased capacity in biobanking and genomics data management and analysis in Africa will enhance regional surveillance of infectious diseases and encourage timely and effective responses to emerging pathogens. 3. Regional whole genome sequence-based surveillance will improve the detection of DR-TB and inform the development of more sensitive and specific rapid diagnostics for the detection and surveillance of DR-TB in Africa and elsewhere. 4. Regional genomic surveillance of malaria parasites will inform a pre-emptive detection of emerging DR parasites and measure the impact of programmatic interventions for a data driven decision making by policy makers. 5. Implementation of harmonized genomic data analysis tools will allow the creation of continent-wide surveillance networks able to identify cross-border spread of DR variants and emerging pathogens. To achieve this, PANGenS will develop genomic epidemiology capacity across Africa by establishing a collaborative framework that brings together all expertise to perform trainings and implementation in all relevant components ranging from wet lab to bioinformatics, and establish proof-of-concept studies for TB and malaria in in selected partner countries",,2027,FORSCHUNGSZENTRUM BORSTEL LEIBNIZ LUNGENZENTRUM,5448291.97,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Disease X | Other | Unspecified,European Commission,Europe,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Germany,,Epidemiological studies,Disease surveillance & mapping,2023 +P23884,101099283,Mobile Bio-Lab to support first response in Arbovirus outbreaks,"The WHO estimates that vector-borne diseases (VBD) account for more than 17% of all infectious diseases. Every year, more than 2.5 billion people are at risk of contracting dengue alone, and VBDs cause almost 1 million deaths. In the last decades several species of invasive disease carrying mosquitoes have invaded the northern hemisphere of the planet through the transport of goods, increasing international travel and climate change. In 2018 a West Nile fever outbreak transmitted by mosquitoes occurred in the EU. For this disease there are no vaccines or medications. There were 1503 cases reported in 11 countries, and 181 deaths. VBD Mobile Bio-Labs could have assisted health authorities in containing this outbreak, reducing cases and preventing deaths. Unfortunately such a system does not exist. MOBVEC will be the first VBD Mobile Bio-Lab, providing: 1- Automatic information about vector populations, obtained in real-time by smart-traps, powered by machine-learning and edge computing: insect species, sex, age, and viral infection. 2- GEOSS compliant vector risk maps of adult insects and eggs/larvae, built on field + Copernicus data; 3- GEOSS compliant disease transmission models in mosquito populations, fusing data from Copernicus, clinical and diagnostic data of reference labs, and vector risk maps; 4- GEOSS compliant citizen-science platform to reinforce the surveillance of mosquitoes using citizens as observation nodes. 5- VBD mobile bio-lab with the capacities of points 1, 2, 3 and 4 + VBD Epidemiological maps and forecast models, to be rapidly operational in the heart of outbreaks to assist first-responders. This technology will the first line of defence against disease vectors worldwide, help prevent and fight devastating disease outbreaks, and will save lives while saving millions of euros in healthcare and lost working-hours. This has never been done before, and our consortium has the interdisciplinary research capacities to make it a reality.",,2027,IRIDEON SL,3268365,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Bunyaviridae | Flaviviridae,,,,,,,,,Other,European Commission,Europe,Europe,Europe,Unspecified,Innovation,,,Spain,,,,2023 +P23888,101075118,"Understanding respiratory tract infections through minimally-invasive, daily nasal sampling in children","Pneumonia is the number one infectious cause of death in children worldwide. Many of the viruses and bacteria that cause pneumonia regularly infect, or colonize, the upper respiratory tract (URT) without causing disease. This drives community transmission but is also an important source of immunity. The processes and key host immune and microbiota factors that determine the infection kinetics, transmission and development of immunity during such infections need elucidation. I have recently optimized minimally-invasive nasal sampling analysis methods using Synthetic Absorptive Matrix (SAM) strips that now allow me to address these knowledge gaps. Through the daily collection of such well-tolerated nasal samples in children, I will study non-pathological, naturally-acquired URT infections, but also controlled infections in an ethical and safe manner using the live attenuated influenza vaccine. In addition, I will perform high frequency nasal sampling in groups of schoolchildren to precisely measure transmission events over time and even infer exposure. Incoming bacteria, viruses and the resident URT microbiome as well as mucosal host innate and adaptive immune responses will be quantified in parallel throughout infections using existing and new high-throughput assays, including an antigen array and microfluidic qPCR for 32 pathogens. Multi-omics integrative time-series analyses and mathematical modelling will be used to identify parameters that are central and predictive for pathogen acquisition, replication and clearance; as well as for transmission and immune boosting. Key novel markers and concepts will be validated using state-of-the-art in vitro mucosal models. The comprehensive and detailed understanding of URT infections obtained in this project can lead to better diagnostics, mucosal targeted therapies and vaccines, and provide a basis for the improved predictions of pathogen spread and public health effects of interventions at the population level.",,2028,ACADEMISCH ZIEKENHUIS LEIDEN,1828865.22,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease transmission dynamics,2023 +P23894,101103640,Strengthening global cooperation and institutional capacities in sub-Saharan Africa to facilitate implementation of the GH EDCTP3 programme,"This proposal is in response to the GH EDCTP3 call for support to EDCTP Africa Office (AO), which is part of the EDCTP Association Secretariat, based in Cape Town and hosted by the South African Medical Research Council. The aim of the proposal is to provide support for the operation of the AO to ensure optimal implementation and visibility of the GH EDCTP3 programme in SSA. The AO will provide technical support, promote networking activities (South-North, South'ÄìSouth), ensure alignment of the funded activities, strategic partnerships, and increase visibility of the GH EDCTP3. This aim of the project will be achieved through several activities that include technical support for the design, implementation and monitoring of capacity developing activities, monitoring funded projects, organising workshops, and facilitating dialogue between African and European research entities and stakeholders. The expected impact is a strengthened and improved delivery of the GH EDCTP3 programme in SSA. The implementation of this proposed project will be structured into four work packages (WP) called Project management (WP1), Capacity development and networking (WP2), Strategic Partnerships (WP3) and Conferences, forums, and meetings (WP4). Through this grant the AO will contribute to the following impacts: Accelerated product development for fighting target infectious diseases; Facilitated preparedness against public health emergencies in line with One Health; Increased visibility of AU-EU partnership in science; Ensured close alignment with SSA national research programmes and activities on target diseases and R&I; Increased participation of SSA countries in GH EDCTP3; and Increased participation of industry and private entities in product development and clinical trials in SSA. To implement the project fully the AO will need a competent Project Coordinator, four Project Officers, a Senior Administrative Officer and an Office Manager. The project will be 2,953,000 euros.",,2025,EUROPEAN & DEVELOPING COUNTRIES CLINICAL TRIALS PARTNERSHIP,3159710,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Infection prevention and control | Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",,2023 +P23904,101125306,"Fighting Pandemics from Below. Global North-South Public Health Cooperation in the Middle East and North Africa, 1792-1942","This project will recapture the lost archives and historical knowledge of international public health cooperation between the 'Äòglobal north'Äô and the 'Äòglobal south'Äô by analysing its first and longest-lasting instances: the sanitary councils in the Middle East and North Africa (MENA). Established in Tangier, Alexandria, Tunis, Istanbul and Tehran, these unprecedented institutions strategised against waves of epidemics and pandemics between the 1790s and the 1940s. Their European, American and native co-founders invented new models for fighting pandemics from below and stopping the diseases in their tracks. They continually strove to overcome the familiar barriers to cooperation posed by inter-imperial competition in a multipolar world, economic inequities, protests against quarantine restrictions and racial and Orientalist biases, among others. In this light, the councils constituted the microcosms of the complex dynamics of north-south health cooperation that also need to be addressed urgently today. However, to date, there has been no in-depth, comparative and longitudinal analysis of their workings. This project will challenge the mainstream narratives by writing an entangled, rather than West-centric, history of health cooperation and by shifting the focus from top-down to bottom-up processes. It will determine what the preconditions for effective international public health cooperation in MENA were and hypothesise that rather than Great Power imposition or veiled imperialism alone, multifaceted reciprocal action induced and sustained sanitary internationalism on the ground. My preliminary data show that the agency of local actors and smaller and medium European powers in accrediting public health cooperation was more central than has been documented to date. This research will test my hypothesis by examining the councils'Äô activity, performance, legitimacy and endurance, and by consulting archival sources in Europe, MENA, North America and Russia.",,2029,UNIVERSITEIT UTRECHT,2180000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience",Policy research and interventions,2024 +P23912,101113261,Consolidation and sustainability of WGS and RT-PCR after HERA support received in 2022 to ensure the integration of enhanced infrastructure into routine surveillance and outbreak investigation,"EU4H-2022-DGA-MS-IBA-01-02 'Äî Consolidation of WGS and RT-PCR activities in Latvia that received support in 2022 aiming to ensure the sustainable use and integration of enhanced infrastructure into routine surveillance and outbreak investigation activities, in synergy with relevant on-going work at international level.",,2026,RIGAS AUSTRUMU KLINISKA UNIVERSITATES SLIMNICA SIA,1049108.65,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Unspecified,,,,,,,,,Unspecified,European Commission,Europe,Europe,Europe,Unspecified,,,,Latvia,,,,2023 +P24195,101003606,Health Emergency Response in Interconnected Systems,"The Corona-virus outbreak is continuing to spread. By beginning of February, the number of infected people surpasses 42,000 infections, and the death toll continues to rise. As authorities and responders are struggling to contain the spread, news about mass quarantine camps or shortages of personal protective equipment threaten the health systems globally, fueled by rumors and mis-information. The disruptions of (medical) supply chains, the lack of capacity to treat patients and the spread of rumours fuel an atmosphere of uncertainty and mistrust, hampering an effective response. While traditional models of disease outbreaks largely focus on infection rates, new methods are needed to integrate behaviour from the bottom up, and integrated in macro-level models to coordinate the response world-wide.",,2023,SVENSKA HANDELSHOGSKOLAN,3112396.9,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,European Commission,Europe,Europe,Europe,Unspecified,,,,Finland,,,,2020 +P24198,INV-064955,"To develop geospatial models to predict the burden of undernutrition among adolescent and pregnant-lactating women (PLWs) in settings affected by Conflict, Climate and Covid-19",N/A,,-99,"Brigham and Women's Hospital, Inc.",40000,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P24201,INV-055339,"to strengthen the impact of HIV and COVID-19 programs in Malawi through enhanced coordination, capacity, and use of digital tools and data systems.",N/A,,-99,Luke International,1272942,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Norway,,Health Systems Research,Health information systems | Health leadership and governance,2023 +P24204,INV-063944,To manufacture Omicron variant SARS-CoV-2 virus to support the development of low-cost effective mucosal vaccines.,N/A,,-99,Naobios,1873800,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P24205,INV-061145,"To develop geospatial models to predict the burden of undernutrition among adolescent and pregnant-lactating women (PLWs) in settings affected by Conflict, Climate and Covid-19",N/A,,-99,Aga Khan University,159457,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Pregnant women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Pakistan,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P24211,INV-060822,To compare functional antibody responses to SARS-CoV-2 vaccination in human vaccinees with human lymph node (LN) chips to evaluate LN chips as a tool for discovery of vaccines.,N/A,,-99,Duke University,200000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2023 +P24214,INV-061385,To reinvigorate high aspirations for the potential of global health investment post-COVID.,N/A,,-99,Duke University,534109,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,,,,United States of America,,,,2023 +P24220,INV-045243,"to support the integration of COVID vaccination into broader, coherent vaccination systems across Kenya",N/A,,-99,United States Fund for UNICEF,2000000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",,2023 +P24221,INV-057608,to coordinate technical assistance for school districts on the use of COVID relief grant funds,N/A,,-99,"Education Resource Strategies, Inc.",300000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2023 +P24223,INV-051738,"to evaluate breadth and duration of protection conferred by OVX836 against seasonal and highly pathogenic influenza strains, informing its potential as a vaccine for long-term prevention of seasonal and pandemic influenza",N/A,,-99,Osivax,1124202,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2023 +P24224,INV-052901,To conduct a review and analysis of the COVID-19 vaccine development literature and interview key contributors to ascertain what lessons could be learned and leveraged to accelerate TB vaccine development.,N/A,,-99,Africa Health Research Institute NPC,33787,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Africa,,"Vaccines research, development and implementation",Vaccine design and administration,2023 +P24225,INV-054254,to characterize the hybrid immunity generated by SARS-CoV-2 infection and inactivated vaccines in Zimbabwean adults with HIV and other comorbidities,N/A,,-99,University of Sheffield,1285161,Human Populations,Black,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P24228,INV-042533,to identify T cell correlates of protection from COVID-19,N/A,,-99,University of Oxford,2493816,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Epidemiological studies | Pathogen: natural history, transmission and diagnostics",Disease susceptibility | Immunity,2022 +P24229,INV-048917,to identify novel compounds targeting henipavirus replication for pandemic antiviral preparedness,N/A,,-99,University of Illinois at Chicago,3101691,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2022 +P24230,INV-050066,to accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,Mylan Laboratories Limited,2000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +P24231,INV-047464,"to showcase an approach for data-driven evidence generation in two large Global South countries, to accelerate clinical translation and global knowledge mobilisation for equitable healthcare, using COVID-19 as an example",N/A,,-99,FIOCRUZ,129932,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,Brazil,,Research on Capacity Strengthening,Systemic/environmental components of capacity strengthening,2022 +P24233,INV-046722,to assess the effects of mitochondrial DNA (mtDNA) haplogroups on SARS-CoV-2 sensitivity,N/A,,-99,Children's Hospital of Philadelphia,2324617,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2022 +P24234,INV-047465,"to understand how COVID-19 has impacted chronic care patients in Haiti, Malawi, Mexico, and Rwanda",N/A,,-99,Partners In Health A Nonprofit Corporation,249989,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P24237,INV-048877,to identify novel compounds inhibiting henipavirus replication for pandemic antiviral preparedness,N/A,,-99,Icahn School of Medicine at Mount Sinai,1996634,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2022 +P24238,INV-051466,To fund the technical transfer and manufacture of public health related vaccines and outbreak/epidemic/pandemic vaccines (excluding COVID-19) on a competitive basis.,N/A,,-99,Aspen Pharma,15000000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2022 +P24239,INV-040440,to identify henipavirus inhibitors and a small animal model of henipavirus replication in BSL-2 containment,N/A,,-99,Katholieke Universiteit Leuven,2729002,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Belgium,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models,2022 +P24240,INV-048922,to solve the henipavirus replicase structure and identify inhibitors of replicase activity for new antivirals for pandemic preparedness,N/A,,-99,University of Oxford,1500036,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history",2022 +P24245,INV-043567,to support global efforts to address learning loss as result of the Covid-19 pandemic related school closures,N/A,,-99,United States Fund for UNICEF,8799184,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P24247,INV-044573,"To build a 06-bed hospital to handle Covid-19 and also other communicable diseases in a tribal district Jhabua, Madhya Pradesh",N/A,,-99,CSIR-Advanced Materials And Processes Research Institute,62500,Not applicable,Not applicable,Not Applicable,Rural Population/Setting,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,,,2022 +P24248,INV-049561,to accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,"YaoPharma Co., Ltd.",3243291,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +P24251,INV-040438,to develop a structural model of Nipah virus replicase to identify allosteric inhibitory sites that serve as starting points for antiviral drug development,N/A,,-99,"Trustees of Boston University, BUMC",2261487,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P24252,INV-045883,to help understand the impact of a collective approach to the covid-19 pandemic,N/A,,-99,International Federation of Red Cross and Red Crescent Societies,800000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Switzerland,,"Policies for public health, disease control & community resilience",,2022 +P24253,INV-049569,"to showcase an approach for data-driven evidence generation in two large Global South countries, to accelerate clinical translation and global knowledge mobilisation for equitable healthcare, using COVID-19 as an example",N/A,,-99,Shaukat Khanum Memorial Trust,120116,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,,,2022 +P24254,INV-051114,to describe the inequities of the COVID 19 response and design a set of interventions that address these going forward,N/A,,-99,Human Sciences Research Council,64991,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Social impacts,2022 +P24255,INV-049859,to use existing COVID data to implement vaccine hesitancy programs for targeted populations in Ethiopia,N/A,,-99,PATH,751416,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2022 +P24257,INV-046743,to better understand how to utilize currently approved COVID-19 vaccines in people living with HIV in order to achieve the most potent and long-lived immune responses,N/A,,-99,Wits Health Consortium (Pty) Ltd,3817329,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation",,2022 +P24258,INV-049853,to accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,Macleods Pharmaceuticals Ltd,2066702,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +P24260,INV-050077,to accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,Hetero Labs Limited,2415000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2022 +P24261,INV-040897,to identify antivirals and host targets for antiviral development targeting henipavirus replication,N/A,,-99,University of Pennsylvania,1888128,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2022 +P24263,INV-047897,To recover the TB delivery programme from Covid-19 losses and support delivery of TB services and reduce TB related mortality in South Africa,N/A,,-99,Genesis Analytics,2753993,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P24264,INV-049262,"to continue support for pathogen discovery and characterization of isolates, including SARS-CoV2",N/A,,-99,University of Chicago,10000,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P24266,INV-048938,to optimize inhibitors of henipavirus N protein for pandemic antiviral preparedness,N/A,,-99,Collaborative Community against Coronavirus (CIC),1931160,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P24267,INV-042469,to develop pan-severe acute respiratory syndrome coronavirus 2 and pan-sarbecovirus vaccines and evaluate in animal models,N/A,,-99,Beth Israel Deaconess Medical Center Inc.,4668146,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P24268,INV-046571,"to continue support for pathogen discovery and characterization of isolates, including SARS-CoV2",N/A,,-99,Prom Health Development Organization,10000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Cambodia,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P24269,INV-045213,"to enable repurposing of a highly effective, user centric contact centre that was conceived for COVID 19 but will be repurposed for other programs",N/A,,-99,The DG Murray Trust,2500422,Not applicable,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2022 +P24270,INV-047732,to contribute to the Uganda Ministry of Health COVID response through a catalytic partnership with the private sector,N/A,,-99,Africa Health Research Institute NPC,94563,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2022 +P24272,INV-002274,to evaluate different COVID vaccine platforms in the lymphoid follicle system in order to better understand how this in vitro system might be used to inform future selections of vaccine platforms for other vaccine antigens,N/A,,-99,Harvard University,852419,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,Not applicable,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine design and administration,2022 +P24273,INV-047025,to advance integrated disease surveillance in the COVID-19 era,N/A,,-99,Joan & Sanford I. Weill Medical College of Cornell University,1000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2022 +P24274,INV-041331,"to advocate for sustained political will and resourcing in the face of pandemic threats, and for building on the lessons of COVID-19 to strengthen global health security going forward",N/A,,-99,Panorama Global,2250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P24276,INV-040444,to develop cell culture and small animal models of Nipah virus replication and pathogenesis,N/A,,-99,CDC Foundation,2791302,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia | Western Pacific,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2022 +P24278,INV-045475,to support genomic surveillance and variants detection of COVID-19 from human and animal sources in South Africa,N/A,,-99,University of Pretoria,1495257,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,Epidemiological studies,"Disease surveillance & mapping | Pathogen genomics, mutations and adaptations",2022 +P24280,INV-043966,"to support countries making plans for integrated disease surveillance in the Covid era, for other diseases as influenza, measles, malaria, and others",N/A,,-99,Instituto Nacional de Sa√∫de,298555,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Mozambique,,Epidemiological studies,Disease surveillance & mapping,2022 +P24281,INV-043962,to support countries making plans for integrated disease surveillance in the COVID era,N/A,,-99,Ministry of Health and Sanitation,299979,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Sierra Leone,,,,2022 +P24282,INV-045996,to support costing and cost-effectiveness analysis of COVID-19 vaccine introduction and deployment strategies in Ghana and Benin in support of broader multi-country policy recommendations,N/A,,-99,"Office of Research, Innovation and Development (ORID)",85000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ghana,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P24283,INV-044708,to support national and sub-national immunization professionals by building their capacity to support immunization programming during COVID-19 recovery,N/A,,-99,Sabin Vaccine Institute,384147,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P24284,INV-037846,to support projects in India for addressing the challenges identified through the Indian experience of managing COVID-19,N/A,,-99,BIRAC,212000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,,,2022 +P24285,INV-040025,To expand auto-disable syringe manufacturing in Africa to stabilize supply for COVID-19 and routine immunization needs in the longer-term on the continent.,N/A,,-99,TKMD Rwanda Ltd,1998774,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Rwanda,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P24286,INV-043825,to support countries making plans for integrated disease surveillance in the Covid era,N/A,,-99,Makerere University School of Public Health,299964,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,,,2022 +P24287,INV-042106,"to deepen the foundation's understanding of development trends as they intersect with COVID related economic recovery, climate change, and geopolitical dynamics",N/A,,-99,Center for Global Development,1050475,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Other secondary impacts,2022 +P24288,INV-040867,To study the combination of fluvoxamine with molnupiravir or Paxlovid in people diagnosed with SARS COV2,N/A,,-99,Certara USA Inc,1532324,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2022 +P24289,INV-040317,to strengthen the linkage between diagnosis and treatment for COVID-19 in Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,4986811,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2022 +P24290,INV-041946,to evaluate the safety and immunogenicity of a full or fractional booster (3rd) dose of a COVID-19 mRNA vaccine in study participants previously vaccinated with either 2 fractional doses or 2 full doses of COVID-19 mRNA vaccines,N/A,,-99,Leiden University Medical Center,300000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +P24291,INV-037877,to support countries making plans for integrated disease surveillance in the Covid era,N/A,,-99,International Association of National Public Health Institutes,399753,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,,,2022 +P24292,INV-028328,"to ensure effective emergency COVID-19 vaccine delivery to African States and enhance access to quality-assured and cost-effective medical commodities, equipment and devices in Africa",N/A,,-99,African Medical Suppliers Platform Limited,3000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Mauritius,,"Vaccines research, development and implementation | Health Systems Research","Vaccine logistics and supply chains and distribution strategies | Health service delivery | Medicines, vaccines & other technologies",2022 +P24293,INV-030827,to expand the availability of gender disaggregated data for COVID and analyze trends by gender,N/A,,-99,Global Health 50/50,499882,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing | Gender,,,United Kingdom,,Epidemiological studies,Disease surveillance & mapping,2022 +P24294,INV-037331,"to support the World Bank in incorporating best practices from Risk Communications and Community Engagement work, as they support countries in getting their citizens access to covid-19 vaccines.",N/A,,-99,International Bank for Reconstruction and Development,500000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Community engagement | Communication,2021 +P24295,INV-038116,to support efforts to expand COVID vaccine availability,N/A,,-99,BIRAC,4500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Health Systems Research,"Medicines, vaccines & other technologies",2021 +P24296,INV-033828,"to evaluate the effectiveness of COVID-19 vaccine for the prevention of symptomatic, reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection among healthcare workers in Kenya",N/A,,-99,University of Oxford,600000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Vaccines research, development and implementation",,2021 +P24298,INV-036746,to enhance the capacity within Pakistan to detect and characterize genomic variants of SARS-CoV2 that threaten public health,N/A,,-99,"National Institute of Health Islamabad, Pakistan",500000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24299,INV-039758,to generate understanding of population levels of immunity to SARS CoV2 in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,3004775,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P24300,INV-037543,to support projects led by organizations in Africa for developing short- and long-term solutions to address misinformation and disinformation associated with COVID-19 and public health communication more broadly,N/A,,-99,South African Medical Research Council,999397,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Policies for public health, disease control & community resilience",Communication,2021 +P24301,INV-035915,to elevate and spread practitioner-driven ideas that support COVID recovery through storytelling,N/A,,-99,"TED Foundation, Inc.",948346,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",,2021 +P24302,INV-038562,to maintain a public database on school/district responses to COVID-19 and create knowledge products that capture learning from these data,N/A,,-99,Arizona State University Foundation for A New American University,600000,Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24303,INV-037365,to generate new data on the gendered impacts of COVID-19 in priority geographies and analyze the economic and social returns on investment in cash and care programs directed towards women,N/A,,-99,"Fraym, Inc.",830704,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,Gender,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P24304,INV-038503,to explore understanding the impact of non-pharmaceutical interventions on the transmission of SARS-COV2,N/A,,-99,University of Washington Foundation,1028520,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2021 +P24305,INV-036064,to support a better understanding of durable immunity to SARS-COV-2 in the context of vaccination and emerging variants,N/A,,-99,University of Washington Foundation,95000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P24306,INV-039881,to conduct robust and rapid COVID-19 vaccine delivery costing studies in 2-3 countries in order to improve budgeting and resource mobilization for vaccine roll-out,N/A,,-99,ThinkWell Institute,300323,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience | Health Systems Research",Vaccine logistics and supply chains and distribution strategies | Policy research and interventions | Health financing,2021 +P24308,INV-037004,to provide interested country governments with data support needed to plan for COVID-19 vaccine delivery and response.,N/A,,-99,Columbia University,2278800,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,,2021 +P24310,INV-036704,to support country partners to utilize existing data when designing their Covid-19 vaccine community engagement projects,N/A,,-99,Common Thread Communications,1750148,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P24311,INV-037498,"to analyze the landscape of cash transfer and care policies in the COVID-19 context - including how care policies affect women'Äôs labor force participation, earnings, and career advancement - and identify good practices globally",N/A,,-99,"Eurasia Group, Ltd.",235000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2021 +P24314,INV-039572,to study the impact of COVID-19 vaccine on routine immunization,N/A,,-99,PATH,98800,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P24315,INV-036322,provide strategic technical assistance to FMOH and 10 focal States to increase oxygen supply/availability (COVID-19 response),N/A,,-99,Clinton Health Access Initiative Inc,1124943,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2021 +P24316,INV-037728,"to implement and validate the LGC ultra high-throughput PCR testing platform for COVID testing and surveillance, as well as for other pathogens important for global health",N/A,,-99,Wits Health Consortium (Pty) Ltd,8777433,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24318,INV-036719,to provide support to public health focused organizations in leveraging social media and digital tools to develop behavior change models to understand barriers and drivers of COVID-19 vaccine uptake,N/A,,-99,Upswell,791315,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +P24319,INV-039970,to advocate for additional global-north development finance in support of economic recovery from COVID-19 in South Asia & Africa low & middle income countries,N/A,,-99,The One Campaign,250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas | Europe,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P24321,INV-036270,to develop and broadly deploy multi-faceted messaging targeting 30% of Nigerians (aged 15+) with the intent of countering misinformation and disinformation and considerably increasing Covid-19 vaccine uptake,N/A,,-99,BBC Media Action,961854,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +P24322,INV-037511,to test the efficacy of a repurposed medicine in the treatment of early covid-19,N/A,,-99,Wits Health Consortium (Pty) Ltd,811670,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Africa,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +P24323,INV-038477,to support world leaders' discussions and boost a new policy unit to work on the following: COVID-19 response; economic recovery; and pandemic preparedness,N/A,,-99,Paris Peace Forum,500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P24324,INV-037810,to support activities that will generate critical information and tools to prepare for the delivery in pregnant women of COVID-19 and other vaccines in low- and middle income countries (LMICs),N/A,,-99,PATH,1425185,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation",,2021 +P24325,INV-038276,to test the ability of topical antibacterial medicines to induce a local innate immune response that is effective in preventing or treating covid-19,N/A,,-99,Yale University,997747,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +P24326,INV-038297,to investigate public opinion changes throughout the COVID-19 pandemic,N/A,,-99,New York University,250000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2021 +P24327,INV-037905,to support the design and implementation of effective non-pharmaceutical (mask) interventions against COVID-19 in South Asia,N/A,,-99,Yale University,2150000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P24328,INV-034765,This project will help develop capabilities for federated data sharing with clinical outcome data from COVID treated patients.,N/A,,-99,The Prince Charles Hospital Foundation,600000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,Data Management and Data Sharing,,,Australia,,,,2021 +P24330,INV-036426,to support the improvement and increment in surge capacity for COVID-19 testing towards COVID-19 pandemic prevention and containment in Nigeria,N/A,,-99,African Field Epidemiology Network,1636718,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24331,INV-038053,to develop low cost of goods sold (COGS) COVID vaccine for low- and middle-income countries (LMICs),N/A,,-99,"Inventprise, Inc.",1577476,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",,2021 +P24332,INV-037884,to ready sites in CHAMPS countries to perform subsequent studies to assess and monitor the effectiveness of vaccines against disease caused by SARS-CoV-2,N/A,,-99,Emory University,786399,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation",,2021 +P24333,INV-039201,to support a collaborative forum for sharing experiences and resources regarding roll out of COVID-19 vaccine in low-income countries,N/A,,-99,Sabin Vaccine Institute,300000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24334,INV-034712,"to support increased mask wearing and vaccinations in Bihar, to help address COVID-19",N/A,,-99,Project Concern International,850000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P24336,INV-034213,to build the resiliency of civil society in Sub-Saharan Africa to weather the COVID-19 pandemic and concurrently elevate women'Äôs voices on health and development issues,N/A,,-99,TrustAfrica,3400000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Senegal,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P24337,INV-037900,to accelerate the early clinical development of novel SARS-CoV-2 Mpro antiviral drug,N/A,,-99,"Calibr, a division of The Scripps Research Institute",6500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2021 +P24338,INV-036204,to leverage behavioral science expertise in South Africa's national COVID 19 vaccine roll out,N/A,,-99,Wits Health Consortium (Pty) Ltd,244685,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Health service delivery,2021 +P24340,INV-025636,"to support health, COVID-19, and Primary Health Care expenditure estimations at country level and a global database on health spending",N/A,,-99,World Health Organization,4800000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,Health Systems Research,Health financing,2021 +P24341,INV-005477,to support large school districts in Covid-19 recovery.,N/A,,-99,Council of the Great City Schools,1750000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24342,INV-036514,to expand pathogen genomic sequencing capacity for genomic surveillance of SARS-CoV-2 in the Rep. of Congo,N/A,,-99,"Fondation Congolaise pour la Recherche Medicale, (F.C.R.M.)",149944,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Congo (DRC),,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24343,INV-038083,to evaluate the effectiveness of COVID-19 vaccines among members of private health insurance plans in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,247518,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation",,2021 +P24344,INV-038739,to support grantee in the project management of the COVAX manufacturing task force that is seeking to unlock manufacturing barriers to increasing supply of Covid vaccines,N/A,,-99,Coalition for Epidemic Preparedness Innovations,400000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Norway,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24345,INV-036531,to support genomic epidemiology of COVID-19 in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,180282,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations",2021 +P24346,INV-038581,to enable genomic surveillance of SARS-CoV-2 in Nepal,N/A,,-99,World Health Organization,149023,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24347,INV-035423,"to strengthen the impact of HIV and COVID-19 programs in Malawi through enhanced coordination, capacity, and use of digital tools and data systems",N/A,,-99,"Cooper Smith Global, LLC",4999935,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Health Systems Research,Health information systems | Health leadership and governance,2021 +P24348,INV-036425,to support optimized adverse event following immunization surveillance for COVID-19 vaccine roll out in Nigeria,N/A,,-99,Sydani Initiative for International Development,1399997,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,"Vaccines research, development and implementation",Adverse events associated with immunization,2021 +P24349,INV-037934,to implement a pilot track-and-trace system for COVID-19 vaccines in Nigeria,N/A,,-99,National Agency for Food and Drug Administration and Control,100000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,"Epidemiological studies | Vaccines research, development and implementation",Disease surveillance & mapping,2021 +P24350,INV-037352,to assist four public hospitals in four districts to support Covid response in Bangladesh,N/A,,-99,SAJIDA Foundation,413359,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2021 +P24351,INV-037937,"to estimate the burden of COVID-19 in Lusaka, Zambia",N/A,,-99,Boston University,1839440,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P24352,INV-030749,"to accelerate the development and launch of critical Rapid Diagnostic Tests for the detection of COVID-19 infection, in order to control the current global pandemic",N/A,,-99,Stanford University,1220791,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24353,INV-034644,to provide COVID-19 response support in Ethiopia with a focus on Risk Communication and Community Engagement approaches to improve adherence to prevention measures and interrupt transmission,N/A,,-99,"JSI Research & Training Institute, Inc.",800000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2021 +P24354,INV-036318,"to evaluate the effectiveness of COVID-19 vaccines in adults living with chronic diseases (diabetes, hypertension and HIV) following routine vaccine introduction in Malawi",N/A,,-99,University College London,962509,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Vaccines research, development and implementation",,2021 +P24355,INV-038731,to generate early data on the next generation 2-8C stable mRNA vaccine candidates against COVID which are critical for the LMICs which have poor ultracold chain capacity,N/A,,-99,PopVax Private Limited,100000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Vaccines research, development and implementation",,2021 +P24356,INV-037711,To support Ministry of Health to conduct a modelling exercise based on population level data to facilitate data driven strategic planning for the COVID vaccine rollout in Ethiopia,N/A,,-99,Quantium Health Outcomes,823600,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Australia,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P24357,INV-032229,to enable operationalization of high-volume manufacturing processes and development of future platforms for COVID-19 diagnostics while also preparing for future pandemics.,N/A,,-99,Global Access Health,4900000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24359,INV-036696,to expand auto-disable syringe manufacturing in Africa to stabilize supply for COVID-19 and routine immunization needs in the longer-term,N/A,,-99,Revital Healthcare (EPZ) Limited,3916512,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P24360,INV-035430,to identify and develop alternative biologics for the prevention and treatment of COVID-19 for low and middle income countries,N/A,,-99,International AIDS Vaccine Initiative Inc,18066005,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P24362,INV-036532,to support SARS-CoV-2 genomic surveillance in Cameroon,N/A,,-99,Centre Pasteur du Cameroun,169100,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Cameroon,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P24363,INV-036839,to build capabilities of grassroots organization for action research and ensure deeper community perspectives in research on post- COVID vulnerabilities for policy influence,N/A,,-99,Self Reliant Initiatives Through Joint Action (SRIJAN),200000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Policies for public health, disease control & community resilience",,2021 +P24364,INV-036731,to determine the impact of COVID-19 on RSV disease,N/A,,-99,Fundaci√≥n INFANT,170072,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Argentina,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P24365,INV-036586,"to conduct rapid mobile phone-based surveys to understand public perception and demand for COVID-19 vaccination, in order to better allocate resources for vaccine delivery",N/A,,-99,University of Cape Town,499401,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Communication,2021 +P24366,INV-036379,to pilot the use of rapid assays for surveillance of known SARS-CoV-2 variants of concern in Africa,N/A,,-99,African Society for Laboratory Medicine NPC,562000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ethiopia,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24367,INV-033028,to deliver drug candidates to be developed for treatment of coronavirus infections including SARS-CoV-2,N/A,,-99,"Novartis Institutes for BioMedical Research, Inc.",2958995,Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P24368,INV-037815,"to develop and validate specimen self-collection devices for use with diagnostic tests for SARS-CoV-2 and other pathogens, with a special focus on usability and human factor design",N/A,,-99,SteriPack (USA) Limited,1250000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24369,INV-037420,to determine the mechanism of SARS-CoV-2 antiviral activity of repurposed compounds in human lung organoids,N/A,,-99,Joan & Sanford I. Weill Medical College of Cornell University,164543,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P24370,INV-036991,"to map out and track in a publicly available and updatable format, DAH and country funding and expenditures for procurement and delivery of COVID-19 vaccines and response",N/A,,-99,University of Washington Foundation,527646,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research","Vaccine logistics and supply chains and distribution strategies | Health financing | Medicines, vaccines & other technologies",2021 +P24373,INV-035299,to support relief and rehabilitation efforts in the context of the second wave of the COVID-19 pandemic in India,N/A,,-99,Self Reliant Initiatives Through Joint Action (SRIJAN),400000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24374,INV-036931,to support countries making plans for integrated disease surveillance in the Covid era,N/A,,-99,Resolve to Save Lives,487114,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2021 +P24375,INV-034780,to build a 30-bed hospital to handle Covid in a tribal district,N/A,,-99,CSIR-Advanced Materials And Processes Research Institute,201260,Unspecified,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Health Systems Research,Health service delivery,2021 +P24377,INV-034652,to understand the epidemiology of SARS-CoV-2 in Brazil,N/A,,-99,Faculdade de Medicina da Universidade de S√£o Paulo,243246,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,Brazil,,Epidemiological studies,,2021 +P24378,INV-038163,to improve the distribution of the COVID-19 vaccine,N/A,,-99,Columbia University,200000,Other,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24379,INV-034621,to provide communication support for Covid-19 messaging in Uttar Pradesh and Bihar,N/A,,-99,Centre for Advocacy and Research,275000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Policies for public health, disease control & community resilience",Communication,2021 +P24380,INV-037531,to support a more coordinated rollout of vaccines through data analytics and Risk Communication and Community Engagement (RCCE) to address hesitancy and to provide support for the COVID-19 Response,N/A,,-99,United States Fund for UNICEF,1494359,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Community engagement | Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +P24381,INV-037938,"to support a multinational study of a combined diagnostic test for SARS-CoV-2 and Mycoplasma tuberculosis, including the use of a self-collected tongue swab specimen as an alternative to nasopharyngeal swab and sputum",N/A,,-99,FIND,2146951,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24382,INV-036530,to support SARS-CoV-2 genomic surveillance in Botswana,N/A,,-99,Botswana Harvard AIDS Institute,172500,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Botswana,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24383,INV-037915,"to support Global Citizen Live and the advocacy efforts around ACTA (Access to Covid Tools Accelerator)/COVAX (Covid-19 Vaccines Global Access), Agriculture adaptation, and gender equality",N/A,,-99,Global Citizen,750000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Gender,,,United States of America,,,,2021 +P24384,INV-036534,to scaling up pathogen genomic sequencing for COVID-19 response in Ethiopia,N/A,,-99,Ethiopian Public Health Institute,172500,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ethiopia,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24385,INV-037058,to evaluate COVID-19 vaccine effectiveness in select countries in Africa and expand WHO AFRO Vaccine Effectiveness Co-ordination Hub,N/A,,-99,World Health Organization Regional Office for Africa,4708323,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Congo,,"Vaccines research, development and implementation",,2021 +P24386,INV-036672,to provide management technical assistance to country COVID-19 vaccine delivery operations centers and the Africa Centers for Disease Control and Prevention to coordinate and execute on large-scale national vaccination rollout.,N/A,,-99,Tony Blair Institute for Global Change,2887500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Vaccines research, development and implementation",,2021 +P24387,INV-034550,"to ensure safety, efficacy, and quality assessment of COVID-related products and their prequalification/emergency use listing",N/A,,-99,World Health Organization,250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,Health Systems Research,"Medicines, vaccines & other technologies",2021 +P24388,INV-033182,"to support the availability of COVID recovery strategies, best practices, and resources for students with disabilities",N/A,,-99,InnovateEDU,3004337,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",,2021 +P24389,INV-038056,to accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,Dr. Reddy's Laboratories Ltd.,1130000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2021 +P24390,INV-035209,to develop and validate multiple specific public health intended uses for an ultra high-throughput PCR (polymerase chain reaction) testing platform for COVID and other pathogens,N/A,,-99,Northwell Health Laboratories,2446125,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24391,INV-036519,to support SARS-CoV-2 genomic surveillance in Oyo State and Nigeria,N/A,,-99,"College of Medicine, University of Ibadan",166118,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24393,INV-033201,To accelerate the manufacturing and availability of a low-cost COVID therapeutic to populations in low- and middle-income countries,N/A,,-99,Cipla,1171900,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2021 +P24394,INV-037533,to provide humanitarian aid to people affected by COVID-19 in Africa,N/A,,-99,AMREF Health Africa,3499989,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,,,2021 +P24395,INV-035995,to evaluate the effectiveness of Pfizer and J&J SARS-CoV-2 vaccines against laboratory-confirmed COVID-19 hospitalisation among risk groups targeted for vaccination,N/A,,-99,Wits Health Consortium (Pty) Ltd,828259,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation",,2021 +P24396,INV-034799,to establish diagnostic technologies in LMICs for the detection of SARS-CoV-2 and other pathogens,N/A,,-99,International Centre for Genetic Engineering and Biotechnology - Italy,2092830,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Unspecified,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Italy,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24397,INV-037532,to provide humanitarian aid to people affected by COVID-19 in Africa,N/A,,-99,African Field Epidemiology Network,6930000,Not applicable,Not applicable,,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,,,2021 +P24398,INV-027248,to increase data and insights on the impact of COVID-19 on workplace giving and share with the field,N/A,,-99,Global Impact,60000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24399,INV-035464,to conduct costing and modeling activities for supporting crucial decisions in South Africa and elsewhere on the prioritized targeting of COVID-19 vaccines for greatest impact,N/A,,-99,Wits Health Consortium (Pty) Ltd,492367,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Epidemiological studies | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Vaccine logistics and supply chains and distribution strategies | Policy research and interventions,2021 +P24400,INV-033021,to provide technical assistance to GoI to support the national COVID-19 vaccination program by streamlining the digital platform deployed.,N/A,,-99,eGovernments Foundation,956530,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,Digital Health,,,India,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +P24401,INV-036328,"to assist countries, suppliers, and procurers make real time adjustments to COVID-19 vaccine and supporting product shipments that optimizes supply based on the dynamic context of a global roll out",N/A,,-99,"JSI Research & Training Institute, Inc.",1617633,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24402,INV-028852,Leveraging Community Radio for localised messaging for COVID-19,N/A,,-99,Seeking Modern Applications for Real Transformation (SMART),362855,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Policies for public health, disease control & community resilience",Communication,2021 +P24403,INV-031044,to develop COVID19 and HIV viral vectored vaccine candidates for potential future clinical evaluations,N/A,,-99,ReiThera,4517386,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Italy,,"Vaccines research, development and implementation",Pre-clinical studies,2021 +P24404,INV-029740,"to strengthen the management, coordination, and effectiveness of HIV prevention programs and the COVID-19 response in Malawi",N/A,,-99,Clinton Health Access Initiative Inc,1500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2021 +P24405,INV-035308,"to evaluate the effectiveness of COVID-19 vaccine for the prevention of symptomatic, RT-PCR confirmed SARS-CoV-2 infection among healthcare workers in Mali",N/A,,-99,"University of Sciences, Techniques, and Technologies of Bamako",327559,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Mali,,"Vaccines research, development and implementation",,2021 +P24406,INV-033847,"to generate epidemiological data on the dynamics of respiratory syncytial virus in the context COVID by magnitude, age, severity, timing and season",N/A,,-99,Wits Health Consortium (Pty) Ltd,277672,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility | Indirect health impacts,2021 +P24407,INV-033821,"to provide technical, logistics, and procurement support to Indonesian laboratories for SARS-CoV-2 sequencing",N/A,,-99,PT. Pandu Biosains,250000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Indonesia,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24408,INV-034057,to develop a COVID-19 assay for disease severity,N/A,,-99,Rockefeller University,99000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P24409,INV-033882,to evaluate effectiveness of the Sinopharm COVID-19 vaccine in healthcare professionals in Mozambique to understand how well the vaccine works and inform policy decisions,N/A,,-99,Instituto Nacional de Sa√∫de,673493,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Mozambique,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Characterisation of vaccine-induced immunity | Policy research and interventions,2021 +P24410,INV-034304,to support Cordaid's activities in the Samenwerkende Hulporganisaties (SHO) campaign alliance for public fundraising efforts for the Covid response,N/A,,-99,Cordaid,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Netherlands,,,,2021 +P24411,INV-030365,"to reduce COVID-19 vaccine hesitancy among health care providers (HCPs) in Nigeria, increase the uptake of COVID-19 vaccines amongst HCPs, and restore confidence in the safe provision of routine essential health services",N/A,,-99,M&C Saatchi World Services LLP,1750047,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +P24412,INV-035305,to support COVID-19: Back the Frontline Initiative,N/A,,-99,Dasra,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2021 +P24413,INV-031411,"to tackle misinformation regarding COVID-19 and the foundation, by injecting credible voices and scientific opinion into the debate to shape the conversation",N/A,,-99,African Population & Health Research Center,45000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,"Policies for public health, disease control & community resilience",Communication,2021 +P24414,INV-025911,to facilitate rapid acquisition of knowledge regarding COVID19 trials that were developing since early 2020.,N/A,,-99,Cytel Canada Health Inc.,50200,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Canada,,,,2021 +P24415,INV-034234,to support the Burkina Faso Ministry of Health to access the between $30 and 60 million of GFATM funding for direct Covid response Disease mitigation and Relevant health and community systems strengthening,N/A,,-99,Pathfinder International,104252,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2021 +P24416,INV-029055,"to measure excess-mortality due to the effects of the COVID-19 pandemic in Karachi, Pakistan using data collected at burial sites",N/A,,-99,University of Texas Southwestern Medical Center,1099535,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas | South-East Asia,,,,,United States of America,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2021 +P24417,INV-004105,"to establish a vibrant hub for economic policy analysis and dialogue, including costing COVID-19 delivery to ensure sustainable reinvigoration of essential health services",N/A,,-99,ThinkWell Institute,4749754,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P24418,INV-031358,"to better characterize COVID-19 in the Global South by integrating real-world COVID-19 data from Brazil into existing harmonized datasets from over 500 million people across the world, to inform local and global control strategies",N/A,,-99,FIOCRUZ,100000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,Brazil,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health information systems,2021 +P24419,INV-034303,to evaluate the effectiveness of COVID-19 vaccines against variants of SARS-CoV-2 in a national immunization program in Bangladesh,N/A,,-99,"International Centre for Diarrhoeal Disease Research, Bangladesh",1280471,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas | South-East Asia,,,,,Bangladesh,,"Vaccines research, development and implementation",,2021 +P24420,INV-031462,"to better characterize COVID-19 in the Global South by integrating real-world COVID-19 data from Pakistan into existing harmonized datasets from over 500 million people across the world, to inform local and global control strategies",N/A,,-99,Shaukat Khanum Memorial Trust,99992,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,Pakistan,,Epidemiological studies,Disease surveillance & mapping,2021 +P24421,INV-034709,to support SARS-CoV-2 sequencing in Zambia,N/A,,-99,PATH,94471,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24422,INV-032575,"to determine whether tissue resident memory T cells, which are found in the nasal cavity during SARS-CoV-2 infection, help limit disease severity and viral replication, and mediate vaccine-induced immunity",N/A,,-99,University of Manitoba,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P24423,INV-031727,"to help promote, coordinate, and facilitate ethical data sharing and use by providing trusted digital research compute environments to researchers seeking to address major questions to reduce the harm of COVID-19 and future pandemics",N/A,,-99,Aridhia Informatics Limited,290020,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United Kingdom,,Epidemiological studies,,2021 +P24424,INV-030342,to evaluate the effectiveness of a COVID-19 vaccine in Health Care Workers in South Africa,N/A,,-99,South African Medical Research Council,2500000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation",,2021 +P24425,INV-029233,"to provide relevant information, analysis, and policy options to address near-term state fiscal challenges precipitated by the COVID-19 pandemic and longer-run structural state budgetary and K-12 finance issues",N/A,,-99,Urban Institute,1500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P24426,INV-032315,to support a project management unit to facilitate multi-stakeholder engagement of traceability efforts for COVID vaccines and beyond,N/A,,-99,PATH,2100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Community engagement,2021 +P24427,INV-034000,to provide bridge funding to CARE to ensure uninterrupted TSU Platform support to GoB to mitigate COVID surge,N/A,,-99,CARE,3500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",,2021 +P24428,INV-034235,to support an age and gender stratified sero-survey study for SARS-CoV-2 in Burkina Faso ahead of the arrival of their COVAX vaccines,N/A,,-99,Clinton Health Access Initiative Inc,475318,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Gender,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P24429,INV-032070,to support genomic surveillance of SARS-CoV-2 in Bangladesh,N/A,,-99,Institute of Epidemiology Disease Control and Research,120871,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Bangladesh,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24430,INV-032027,to support the Fund for Public Schools and NYC Department of Education in leveraging strategic partnerships to successfully recover from COVID-19 and re-engage students in learning in 2021 and 2022,N/A,,-99,Fund for Public Schools Inc,500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24431,INV-032001,to help determine the true number of people infected with SARS-CoV-2 in Kenya and Tunisia by developing epidemiological models to implement wastewater SARS-CoV-2 surveillance in diverse sanitation settings,N/A,,-99,Institut Pasteur de Tunis,201986,Human Populations | Environment,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Tunisia,,Epidemiological studies,Disease surveillance & mapping,2021 +P24432,INV-031229,to identify potent monoclonal antibodies to protect against COVID-19 in low and middle income countries,N/A,,-99,Columbia University,298807,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2021 +P24433,INV-031519,to provide donor-coordinated technical assistance to support South Africa's national COVID-19 vaccine roll out plan,N/A,,-99,The DG Murray Trust,950000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +P24434,INV-031996,"to rapidly discover and develop potent, orally available, small molecule inhibitors of the main protease (Mpro) of SARS-CoV-2 using artificial intelligence-driven structure guided drug design",N/A,,-99,Exscientia AI Limited,767100,Other,Not applicable,Not Applicable,Not applicable,Not applicable,,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P24435,INV-033701,to enable the expansion of the International COVID-19 Data Alliance workbench for COVID data analysis to low and middle income country partners,N/A,,-99,Health Data Research UK,577246,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United Kingdom,,,,2021 +P24436,INV-030309,to assess and measure all-cause excess mortality in the COVID-19 epidemic in key low and middle-income country geographies by leveraging the systematic data collection in health and demographic surveillance sites,N/A,,-99,Wits Health Consortium (Pty) Ltd,2906550,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,South Africa,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2021 +P24437,INV-031078,"to understand the impact of COVID-19 pandemic on reproductive, maternal, newborn and child health and nutrition in sub-Sahara Africa",N/A,,-99,Johns Hopkins University,1089609,Human Populations,Black,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P24438,INV-034069,to provide urgent assistance to respond to the COVID-19 pandemic in Bangladesh,N/A,,-99,United States Fund for UNICEF,1000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2021 +P24439,INV-032429,"to examine multiple dimensions of global malaria efforts in the context of COVID-19 disruptions, while the foundation's specific contribution is for the inclusion of endemic country voices in the discourse",N/A,,-99,Harvard T.H. Chan School of Public Health,75000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P24440,INV-034118,to provide urgent assistance to respond to the COVID-19 pandemic in Nepal,N/A,,-99,United States Fund for UNICEF,650000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2021 +P24441,INV-029226,to provide communications support for COVID-19 vaccine roll-out in India,N/A,,-99,United States Fund for UNICEF,2009160,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Communication,2021 +P24442,INV-033582,"to rapidly mobilize solutions for COVID-19 across multiple domains such as: prevention of covid-19 spread, scale up testing, support for healthcare workers & hospitals, management of critically ill patients",N/A,,-99,United Way Worldwide,3382593,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2021 +P24444,INV-030411,to provide technical assistance to low- and low-middle income countries' COVID-19 vaccine and diagnostics programs and support COVAX communications to participating countries,N/A,,-99,Clinton Health Access Initiative Inc,3300000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Communication | Systemic/environmental components of capacity strengthening,2021 +P24445,INV-031351,to fund data analysis of a unique repository of health care outcomes data for COVID patients,N/A,,-99,Health Care Cost Institute Inc,1388497,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,,2021 +P24446,INV-033576,to provide respiratory care support to State governments of UP and Bihar towards improved COVID-19 response and long term system readiness.,N/A,,-99,PATH,2350000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Health Systems Research | Secondary impacts of disease, response & control measures",Health service delivery | Indirect health impacts,2021 +P24447,INV-032725,to establish human organ chip model in BSL3 lab to assess potential Covid19 therapeutics,N/A,,-99,Wits Health Consortium (Pty) Ltd,392640,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics",Disease models,2021 +P24448,INV-031753,"to finance independent data collection, research and analysis, and convening on post-Covid reform processes to strengthen global preparedness for potential pandemics",N/A,,-99,Foundation for the Graduate Institute of International and Development Studies,374946,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,,,2021 +P24449,INV-030597,to support design and development of Covid-19 vaccination campaign in Bangladesh,N/A,,-99,United States Fund for UNICEF,323150,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P24450,INV-028353,"to establish data standards, specifications, and guidance for COVID immunization data systems",N/A,,-99,World Health Organization,500000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,Health Systems Research,Health information systems,2021 +P24451,INV-032693,to respond to requests from COVAX countries for assistance in determining which open-source digital tools are best suited for country COVID response plans and create costed roadmaps for implementation of COVID-19 related system needs,N/A,,-99,United States Fund for UNICEF,699586,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P24452,INV-030223,"to complete the development of a fast, cost, effective diagnostic system that will enable rapid quantification of SARS-CoV-2 pathogens in environmental samples, through analysis at the point of sampling",N/A,,-99,California Institute of Technology,599983,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Environmental stability of pathogen,2021 +P24453,INV-032019,to identify broad-spectrum antiviral drugs that trigger an innate immune response and could be used against a range of viruses such as SARS-CoV by using a computational approach to analyze drug repurposing libraries,N/A,,-99,University of Michigan,100000,Other,Unspecified,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P24454,INV-032620,to support a fund that will strengthen primary healthcare systems in Southeast Asia to mitigate the impact of COVID-19 and future pandemics,N/A,,-99,Asian Venture Philanthropy Network Limited,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Singapore,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P24455,INV-029897,this investment will be used to disseminate evidence and policy recommendations for a gender-intentional economic recovery from COVID-19,N/A,,-99,The Slate Group LLC,721432,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,Gender,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P24456,INV-030330,to identify potent escape-resistant human monoclonal antibodies that prevent COVID-19 for use in low and middle-income countries,N/A,,-99,University of North Carolina at Chapel Hill,396373,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2021 +P24458,INV-024915,To investigate Covid re-infection rates and immune correlates of disease,N/A,,-99,Christian Medical College Vellore,1945605,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +P24459,INV-031859,to secure and provide WHO AFRO with needed project management support for its COVID vaccine pillar to help drive and monitor access to COVID vaccines across sub Saharan Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,936983,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P24460,INV-017324,"to increase demand for effective PHC in Nigeria in a COVID-impacted context, by improving adoption and application of behavioral science approaches used by NPHCDA, SPHCDAs (at scale and in 10 focus states) and Community Influencers",N/A,,-99,Busara Center for Behavioral Economics,999789,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P24462,INV-026701,to fund deployment of a previously developed tool to support patient flow analysis to support smooth operation of primary healthcare services during and post Covid-19,N/A,,-99,The William Davidson Institute at the University of Michigan,525116,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,,,2021 +P24463,INV-031050,"to commit additional vaccine production to the COVAX Advance Market Commitment of Gavi, the Vaccine Alliance, a financing mechanism through which Gavi aims to secure equitable access to COVID-19 vaccines for 92 LMIC",N/A,,-99,"Inventprise, Inc.",612000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Research to inform ethical issues | Vaccines research, development and implementation",Research to inform ethical issues in the Allocation of Resources,2021 +P24464,INV-030409,to disseminate rapid learning from COVID-19 vaccine rollout through Sabin'Äôs Boost Community,N/A,,-99,Sabin Vaccine Institute,350000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Communication,2021 +P24465,INV-030336,"to improve durability, efficacy and deliverability of COVID-19 vaccines",N/A,,-99,Instituto D'OR de Pesquisa e Ensino,8908890,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Brazil,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24466,INV-028205,to support Tacoma Public Schools to adapt to the COVID-19 pandemic,N/A,,-99,Tacoma Public Schools,149958,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24467,INV-030886,to secure and provide to the African Vaccines Regulatory Forum (WHO AFRO) needed project management support for its process to help expedite national regulatory registration of COVID-19 vaccines,N/A,,-99,Wits Health Consortium (Pty) Ltd,529763,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P24468,INV-029122,to build tools and information for use by the field and policymakers to respond to fiscal impacts associated with the COVID-19 pandemic on state K-12 funding streams,N/A,,-99,"Bellwether Education Partners, Inc.",500009,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P24469,INV-028206,to support Kent School District to adapt to the COVID-19 pandemic,N/A,,-99,Kent School District #415,149360,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24470,INV-029062,to contribute to improved understanding of the epidemiology of COVID-19 in India,N/A,,-99,"The Center for Disease Dynamics, Economics & Policy, Inc.",800003,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,Epidemiological studies,,2021 +P24471,INV-030072,to better understand the risks and external costs of the COVID-19 vaccine rollout,N/A,,-99,PATH,99796,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24472,INV-028213,to support Edmonds School District to adapt to the COVID-19 pandemic,N/A,,-99,Edmonds School District No 15,150000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24473,INV-029778,to complete analysis and scientific writing related to data on the COVID SA variant,N/A,,-99,Wits Health Consortium (Pty) Ltd,100000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P24474,INV-025157,"to provide technical support to the Senegal Covid-19 Task Force and to establish an Innovation Investment Facility, a facility that is entirely dedicated to Covid 19-related innovative schemes with a focus on women's businesses",N/A,,-99,Pathfinder International,600000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Gender,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P24475,INV-028322,to support a learning community for Washington state school districts to improve their COVID-19 adaptations,N/A,,-99,Education First Consulting LLC,615744,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24476,INV-028214,to support Everett Public Schools to adapt to the COVID-19 pandemic,N/A,,-99,Everett Public Schools,135000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24477,INV-028208,to support Federal Way Public Schools to adapt to the COVID-19 pandemic,N/A,,-99,Federal Way School Dist 210,108756,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24478,INV-028210,to support Yakima School District to adapt to the COVID-19 pandemic,N/A,,-99,Yakima School District #7,159998,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24479,INV-028212,to support Evergreen School District to adapt to the COVID-19 pandemic,N/A,,-99,Evergreen School District No. 114,150000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24480,INV-028159,"to support the Immunization Division, Ministry of Health and Family Welfare, Government of India to roll out COVID-19 vaccines in India with efficiency and effectiveness",N/A,,-99,"JSI Research & Training Institute, Inc.",4999048,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation",,2021 +P24481,INV-028186,to support Highline Public Schools to adapt to the COVID-19 pandemic,N/A,,-99,Highline Public Schools,150005,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24482,INV-028204,to support Spokane School District to adapt to the COVID-19 pandemic,N/A,,-99,Spokane Public Schools,150000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P24483,INV-025789,to provide technical assistance to the Government of India to smoothly roll-out Covid19 vaccines across the country,N/A,,-99,World Health Organization India Country Office,2800000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Policies for public health, disease control & community resilience | Health Systems Research","Vaccine/Therapeutic/ treatment hesitancy | Medicines, vaccines & other technologies",2021 +P24484,INV-027027,to accelerate COVID19 vaccine distribution in India by Ministry of Health and Family Welfare,N/A,,-99,Indian Institute of Technology Delhi,500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P24485,INV-027991,to support community outreach in Ohio's statewide COVID-19 communications campaign,N/A,,-99,Health Is Everybodys Business Inc,500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2021 +P24486,INV-024562,"to reduce the impact of the COVID-19 pandemic within low-income, lower-middle income, and IDA-eligible upper-middle income economies by accelerating the introduction and scale up of vaccines that protect against COVID-19",N/A,,-99,GAVI Alliance,200000000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2020 +P24489,INV-025755,to support the Africa Union to develop a gender intentional COVID-19 response,N/A,,-99,New Venture Fund,499403,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Gender,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24490,INV-022851,To support an effective COVID-19 response in Bangladesh,N/A,,-99,Food and Agriculture Organization of the United Nations,400000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Italy,,,,2020 +P24491,INV-021366,"to support the use of big data, predictive data analysis and artificial intelligence in the response to COVID-19",N/A,,-99,Wadhwani Institute for Artificial Intelligence Foundation,224825,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,Data Management and Data Sharing,,,United States of America,,,,2020 +P24492,INV-023270,to measure antibody persistence to COVID infection in Mumbai,N/A,,-99,BIRAC,206000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P24493,INV-025372,to develop COVID19 synthetic data for sharing,N/A,,-99,"Syntegra, Inc.",40000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,,,2020 +P24494,INV-021499,to collect data on and develop insights into the experiences of Americans as they deal with the public health crisis and economic shocks engendered by the COVID-19 outbreak as well as crossroads moments in their lives,N/A,,-99,Stanford University,770000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P24495,INV-005891,strengthen family planning interventions informed by learnings from state and sub-state levels including COVID-related essential service provisions insights from five states,N/A,,-99,Ipas Development Foundation,1362436,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24496,INV-018603,to development of a COVID-19 therapeutic approach,N/A,,-99,BioNTech SE,4918943,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24497,INV-022681,to promote equitable access to scientific information and treatments for the most vulnerable populations affected by COVID-19,N/A,,-99,Multiplier,440000,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P24498,INV-024267,to rapidly test therapeutic antibodies in human organoid tissue cultures for efficacy to block infection with SARS-CoV-2,N/A,,-99,Stanford University,685042,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24499,INV-021495,"to provide support to Mumbai municipal corporation to tackle COVID-19 pandemic in the city's slums, COVID hotspots and containment zones",N/A,,-99,Bharatiya Jain Sanghatana,325050,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,,,2020 +P24500,INV-022986,"to advance the R&D and market expansion models of innovative enterprises leading the digitization of fortification quality, while addressing the impact of COVID on access to fortified foods by vulnerable populations",N/A,,-99,World Food Programme,2500000,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,Italy,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +P24501,INV-023552,"to understand how the COVID-19 pandemic is changing postsecondary student enrollment, admissions policies and strategies, institutional pricing, and financial aid practices",N/A,,-99,University of Southern California,477574,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24502,INV-022787,"to develop a rapid, sensitive and easily deployable molecular diagnostic device for affordable SARS-CoV-2 detection in LMICs",N/A,,-99,"Sherlock Biosciences, Inc.",5900142,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24503,INV-025345,to provide field support (personnel) to manage DRC's 11th EVD outbreak,N/A,,-99,University of Nebraska Medical Center,672752,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Filoviridae,,,,,,,,,Ebola virus disease,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24504,INV-021448,to provide thought leadership and evidence on the international development finance needed to support an inclusive recovery from the COVID-19 crisis,N/A,,-99,ODI,1750000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P24505,INV-017374,to support bridging and bonding across key GPA PE&I and PPT constituents in a post-COVID world,N/A,,-99,"University of California, Berkeley",500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",,2020 +P24506,INV-023945,to develop resources for state-level Chief Data Officers and other state officials to improve data culture within states and better understand and address the economic impacts of the COVID-19 pandemic,N/A,,-99,Georgetown University,1180761,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24507,INV-023725,to support clinical development of COVID-19 vaccines by Chinese manufacturers in order to bolster supply of prequalified COVID-19 vaccines available for global health purposes,N/A,,-99,PATH,2500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",,2020 +P24508,INV-024609,to evaluate impact of SARS-CoV-2 on ACE2 and NAD metabolism pathways in a human intestine model,N/A,,-99,University of Virginia,315888,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Disease pathogenesis,2020 +P24509,INV-018252,to evaluate the impact of vaccine candidates and antibodies on COVID-19 disease outcomes and immune responses,N/A,,-99,Alternative Energies and Atomic Energy Commission,976737,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Immunity,2020 +P24511,INV-022827,"to support the collation of relevant data, production of models, and dissemination of results on projections of COVID-19 impact for the world",N/A,,-99,University of Washington Foundation,2487121,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24512,INV-024236,to support the COVID Response implementation of high quality resources through building effective and sustainable virtual communities of practice,N/A,,-99,"Center for Educational Effectiveness, Inc.",798263,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24513,INV-024911,to characterize the seasonality of the SARS-CoV2 virus is different setting around the world to best support mitigation efforts,N/A,,-99,The University of Southampton,476214,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,Epidemiological studies,Disease surveillance & mapping,2020 +P24515,INV-023825,"to characterize the prevalence of SARS-CoV-2, TB co-infection, and impact of SARS-CoV-2 co-infection on TB treatment response in TB endemic regions",N/A,,-99,Stellenbosch University,504814,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus | Other,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,South Africa,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2020 +P24516,INV-018557,"to support the office of the President of Burkina Faso in rethinking, redesigning, and implementing an updated HCD agenda, which has been severely affected by the Covid-19 pandemic",N/A,,-99,Tony Blair Institute for Global Change,1016126,Unspecified | Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,,,2020 +P24517,INV-023868,to support research on the ways in which COVID-19 has and will continue to impact K-12 education,N/A,,-99,Rice University,120000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24518,INV-023708,to research and test potential therapeutics to treat or eliminate mild COVID-19,N/A,,-99,Gates Medical Research Institute,3971404,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24519,INV-025422,to supplement the Municipal Corporation of Greater Mumbai (MCGM)'Äôs efforts to integrate and align RAT and RT-PCR testing strategies allowing for an effective and efficient approach for diagnosis of COVID-19,N/A,,-99,FIND,408879,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Switzerland,,,,2020 +P24520,INV-025462,"to translate research from the under-five mortality project into policy and program support for countries, and to evaluate the resilience of evidence-based interventions to reduce U5M during the COVID-19 pandemic",N/A,,-99,University of Global Health Equity,243487,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,,,,Rwanda,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Policy research and interventions,2020 +P24521,INV-018285,to understand the economic impacts of COVID-19 on poor and vulnerable communities in Indonesia,N/A,,-99,International Bank for Reconstruction and Development,509247,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24522,INV-023515,to research the impact of covid19 on learning losses in Ethiopia,N/A,,-99,University of Cambridge,420000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24523,INV-021348,to support availability of awareness of resources that support students with disabilities during distance learning due to COVID-19,N/A,,-99,National Center for Learning Disabilities,293998,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24526,INV-023946,"to develop resources for city-level government leaders to better understand and address the economic impacts of the COVID-19 pandemic, and develop equitable recovery plans for the future",N/A,,-99,"National League of Cities, Institute for Youth, Education and Families",2218229,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24527,INV-025321,to inform sampling strategies for pathogen genomic sequencing for SARS-CoV-2 and Cholera.,N/A,,-99,Johns Hopkins University,98685,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24528,INV-024494,to support the 2020 COVID-19 Resiliency Fund,N/A,,-99,Latino Community Fund Of Washington State,200000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24529,INV-024501,to support the COVID-19 Response and Recovery Fund,N/A,,-99,United Way Of Benton & Franklin Counties,200000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24530,INV-024506,to support the Washington State COVID-19 Relief Fund for Undocumented Individuals,N/A,,-99,Scholar Fund,200000,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24532,INV-026161,To support understanding of immune response to SARS CoV 2 in low and middle income countries,N/A,,-99,Wits Health Consortium (Pty) Ltd,60490,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P24533,INV-025996,"to secure African political leadership endorsement of interventions at the national level to accelerate regulatory approval of safe, efficacious, and quality manufacturer COVID-related vaccines and therapeutics",N/A,,-99,Wits Health Consortium (Pty) Ltd,385000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24534,INV-026231,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Tuskegee University,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24535,INV-021779,"to understand the epidemiology of COVID-19 in Kibera, Kenya",N/A,,-99,CDC Foundation,971885,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Epidemiological studies,,2020 +P24536,INV-019507,"to deepen decision makers'Äô understanding of the gendered impacts of the COVID-19 pandemic, by synthesizing evidence on economic and social responses, and identifying evidence-based solutions to address gender inequities",N/A,,-99,Center for Global Development,1445467,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Gender,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts,2020 +P24537,INV-025385,"To ensure safety, efficacy, and quality assessment of COVID-related products and their prequalification/emergency use listing.",N/A,,-99,World Health Organization,250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,Health Systems Research,,2020 +P24538,INV-023006,to estimate excess deaths due to COVID 19 in Bangladesh.,N/A,,-99,"International Centre for Diarrhoeal Disease Research, Bangladesh",817537,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,Epidemiological studies,Disease surveillance & mapping,2020 +P24539,INV-023809,to fund a common fund which will engage local private and public founders in a joint effort to set up a grant-making common fund post COVID-19,N/A,,-99,Beijing New Sunshine Charity Foundation,635315,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,"Secondary impacts of disease, response & control measures",,2020 +P24540,INV-023918,to collect survey data on COVID impacts on GBV in different countries,N/A,,-99,UN Women,834462,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24541,INV-023681,to develop a portal with hyperlocal data on the drivers of COVID vulnerability that will equip local leaders and policymakers with information on how to best serve disproportionately impacted regions and populations in the United States,N/A,,-99,"Surgo Ventures, Inc.",1326719,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,Epidemiological studies,Disease susceptibility,2020 +P24542,INV-018417,to understand imaging measures of COVID-19 disease severity in non-human primates,N/A,,-99,University of Pittsburgh,109498,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics,2020 +P24543,INV-019355,to develop an anti-SARS-CoV-2 mAb product for prevention of severe COVID-19 in vulnerable populations in low and middle income countries,N/A,,-99,Columbia University,2499588,Unspecified,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24544,INV-023398,to evaluate and advance a novel technological platform to increase the potency and breadth of monoclonal antibodies against SARS-CoV-2 and other infectious disease agents,N/A,,-99,Hospital for Sick Children,7323359,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Canada,,"Therapeutics research, development and implementation",,2020 +P24545,INV-022587,to accelerate the development and launch of critical Rapid Diagnostic Tests for the detection of COVID-19 infection in order to control the current global pandemic,N/A,,-99,"Pine Trees Health, Inc.",499968,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24546,INV-023811,to support the exploratory development project of a low cost dry powder inhalation for the treatment of COVID19.,N/A,,-99,"Hovione FarmaCiencia, S.A.",586201,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Portugal,,"Therapeutics research, development and implementation",,2020 +P24547,INV-024495,to support a survey on the disruption of COVID 19 on education,N/A,,-99,International Association for the Evaluation of Educational Achievement,238000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24548,INV-006369,to look into the impact of COVID-19 to Chinese philanthropic giving and aims to share useful content and direction to the philanthropic community,N/A,,-99,Centre for Asian Philanthropy and Society Ltd.,199801,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Hong Kong,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P24549,INV-026234,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Texas Southern University Foundation,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24550,INV-024130,to enable evidence generation in Ghana about COVID-19 risk and seroprevalence,N/A,,-99,College of Basic and Applied Sciences,99876,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ghana,,Epidemiological studies,Disease surveillance & mapping,2020 +P24551,INV-021489,to support the aggregation and vetting of resources for students with special needs during COVID-19 as well as community-building for educators of students with special needs,N/A,,-99,InnovateEDU,571080,Human Populations,Not applicable,Unspecified,Unspecified,Vulnerable populations unspecified | Other | Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24552,INV-024240,to support countries with necessary evidence to mitigate impact of COVID-19 on neonatal mortality,N/A,,-99,Living Goods,395989,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24553,INV-022917,to accelerate the development of a COVID-19 direct antigen test available at an affordable price to LMIC populations,N/A,,-99,DCN Diagnostics,1054244,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Diagnostics | Medicines, vaccines & other technologies",2020 +P24554,INV-026042,to better understand demand and to identify and address roadblocks to accessing antigen rapid diagnostic tests for COVID-19,N/A,,-99,Clinton Health Access Initiative Inc,49815,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Health Systems Research,Health service delivery,2020 +P24555,INV-025247,to develop a privacy preserving service for reporting exposure notification to public health for Covid-19,N/A,,-99,Internet Security Research Group,358722,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Research to inform ethical issues | Health Systems Research,Research to inform ethical issues in Research | Health information systems,2020 +P24556,INV-017894,"to leverage Uganda's Malaria Research Centres for enhanced malaria surveillance in the time of COVID-19, to understand how the pandemic is affecting malaria transmission and treatment-seeking",N/A,,-99,University of California San Francisco,192150,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24557,INV-022653,to support effective response to vulnerable communities affected by COVID-19 in Bangladesh,N/A,,-99,BRAC,299754,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,,,2020 +P24558,INV-022039,to support research on the ways in which COVID-19 has and will continue to impact K-12 education,N/A,,-99,University of Florida,145797,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24559,INV-021423,to support R&D for COVID-19 response,N/A,,-99,Serum Institute of India,4000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,,,2020 +P24560,INV-023772,to create more equitable school finance systems as states respond to the short- and long-term impacts of the COVID-19 pandemic,N/A,,-99,Learning Policy Institute,300172,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Health Systems Research",Health financing,2020 +P24561,INV-022037,to support research on the ways in which COVID-19 has and will continue to impact K-12 education,N/A,,-99,Vanderbilt University,110214,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24562,INV-025211,to support high-level dialogue and boost coordinated global policies on how to respond to the COVID-19 pandemic,N/A,,-99,Paris Peace Forum,349451,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,,,2020 +P24563,INV-023576,"to shorten the shipment times for polio and COVID-19 test samples and jump start a sustainable, integrated drone program in CAR",N/A,,-99,VillageReach,399943,Unspecified,Unspecified,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2020 +P24564,INV-006373,To strengthen the research of vaccine safety and pharmacovigilance for COVID-19 vaccine and NIP vaccine in China,N/A,,-99,Chinese Preventive Medicine Association,1079982,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,"Vaccines research, development and implementation",,2020 +P24565,INV-004949,"to leverage mutational antigenic profiling to advance the design of vaccines and therapeutics to SARS-CoV-2, influenza virus and HIV",N/A,,-99,Fred Hutchinson Cancer Center,899997,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P24566,INV-021349,"to inform the field about different strategies, practices, and school models implemented during the COVID-19 crisis that may better support education for students with disabilities in the long-term",N/A,,-99,University of Washington Foundation,400743,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24567,INV-025642,to evaluate the availability of CO2 in Africa will help the development of strategies for equitable distribution of Covid-19 candidate vaccines requiring ultra cold chain,N/A,,-99,Global Environment & Technology Foundation,99999,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation | Health Systems Research",Vaccine logistics and supply chains and distribution strategies | Vaccine trial design and infrastructure | Health service delivery,2020 +P24569,INV-023942,"to support global vaccine delivery efforts including access, introduction, and scale of COVID-19 vaccines in countries eligible for the COVAX AMC",N/A,,-99,Dalberg Catalyst,2812976,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2020 +P24570,INV-023198,to expand manufacturing capacity of Covid-19 direct antigen RDTs to better serve demand in low and middle income countries.,N/A,,-99,"Access Bio, Inc.",400000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Secondary impacts of disease, response & control measures",Diagnostics | Other secondary impacts,2020 +P24571,INV-023013,to model the potential impact of rapid diagnostics for COVID-19,N/A,,-99,Imperial College London,140041,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United Kingdom,,Epidemiological studies,Impact/ effectiveness of control measures,2020 +P24572,INV-022038,to support research on the ways in which COVID-19 has and will continue to impact K-12 education,N/A,,-99,American Institutes for Research,3255670,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24573,INV-023650,to forecast 3-month incidence of COVID 19 for 60-120 countries in order to assist COVID-19 vaccine developers with clinical trial site selection,N/A,,-99,Northeastern University,90000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24575,INV-023210,"to understand how the social and other indirect impacts of COVID-19 (social distancing, quarantine, etc) and perceptions of risk impact sexual risk behavior that could lead to HIV",N/A,,-99,Imperial College London,2178260,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P24576,INV-023030,to test antiviral compounds in hamster infection model for COVID-19,N/A,,-99,Icahn School of Medicine at Mount Sinai,524865,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24577,INV-024617,to develop an anti-SARS-CoV-2 mAb product for prevention of severe COVID-19 in vulnerable populations in low and middle income countries,N/A,,-99,Academisch Medisch Centrum,223307,Unspecified,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Netherlands,,"Therapeutics research, development and implementation",,2020 +P24578,INV-023853,"to help districts understand scope, timing, and substance of forthcoming financial decisions precipitated by COVID-19",N/A,,-99,Georgetown University,349594,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24579,INV-025171,to help the government coordinate between different ministries and sub-nationally to support the COVID19 and other foundation priority diseases response and prevent disease among the poor and marginalized.,N/A,,-99,Roshan Aaj - Akhter Hameed Khan Foundation,1470276,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,Infection prevention and control,,2020 +P24580,INV-022349,to support the Puget Sound Educational Service District on COVID-19 related reentry and recovery planning and training,N/A,,-99,Puget Sound Educational Service District,85000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24581,INV-023718,to support the development of two reports during the 20-21 school year on how students are experiencing the COVID-19 pandemic,N/A,,-99,"Center for Effective Philanthropy, Inc.",400000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24582,INV-023719,to maintain a public database on school/district responses to COVID-19 focused on social emotional learning and create knowledge products that capture learning,N/A,,-99,University of Washington Foundation,250000,Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24583,INV-017749,to support strengthening of Mozambique'Äôs COVID-19 response and essential health services continuity,N/A,,-99,ThinkWell Institute,1325687,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Health Systems Research,Health service delivery,2020 +P24584,INV-019149,"to increase the capacity of Emergency Operations Centers in Burkina Faso, Cote d'Ivoire, Cameroon and Niger to respond to direct and indirect effects of COVID-19 through strengthened systems for data integration and use",N/A,,-99,BlueSquare,4499986,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Data Management and Data Sharing,,,Belgium,,"Secondary impacts of disease, response & control measures",,2020 +P24585,INV-024653,to support analysis of COVID-19 impacts to state Pre-K,N/A,,-99,Education Commission of the States,50000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24586,INV-003438,"to catalyze the introduction and uptake of a point-of-care diagnostic testing platform and high-quality, rapid COVID-19 direct antigen tests across African countries",N/A,,-99,LumiraDx UK Limited,17000000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24587,INV-018954,to characterize the longitudinal immune response to SARS-CoV-2 in a Bangladeshi population,N/A,,-99,"International Centre for Diarrhoeal Disease Research, Bangladesh",1157166,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,Epidemiological studies,Disease surveillance & mapping,2020 +P24588,INV-021602,"to develop and implement methods for SARS-CoV-2 detection and quantification in low and middle income countries, with a focus on populations not connected to underground sewers",N/A,,-99,PATH,2579261,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2020 +P24589,INV-024933,to support effective and efficient implementation of the LumiraDx platform and COVID-19 antigen tests across 14 initial countries in sub-Saharan Africa,N/A,,-99,Clinton Health Access Initiative Inc,1837022,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24590,INV-023690,"to leverage Uganda's Malaria Research Centres for enhanced malaria surveillance in the time of COVID-19, to understand how the pandemic is affecting malaria transmission and treatment-seeking",N/A,,-99,Infectious Diseases Research Collaboration,207494,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24591,INV-023833,to understand public perceptions of COVID-19 vaccines in Africa,N/A,,-99,London School of Hygiene and Tropical Medicine,198896,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2020 +P24592,INV-004739,to implement a network of schools and local partners in Seattle focused on responding to COVID related academic and social emotional challenges,N/A,,-99,Seattle University,2500000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24593,INV-018928,to support the Florida Chamber Foundation to host a series of regional business roundtables and convenings to inform strategic planning for post COVID recovery,N/A,,-99,Florida Chamber of Commerce Foundation Inc,125000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",,2020 +P24594,INV-006367,to provide technical support and scientific tools in preparation for the potential COVID-19 vaccine implementation in China,N/A,,-99,Duke University,303306,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas | South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation",,2020 +P24595,INV-021773,to strengthen the ability of Mozambique'Äôs communicable disease surveillance system to track and respond to direct and indirect impacts of COVID-19,N/A,,-99,Clinton Health Access Initiative Inc,1289415,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping,2020 +P24596,INV-019364,to help journalists better cover the COVID-19 pandemic in Africa by building a data hub that will improve their ability to identify stories and use visualizations and interactives in their coverage,N/A,,-99,Open Cities Lab,1601452,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Data Management and Data Sharing,,,South Africa,,"Policies for public health, disease control & community resilience",Communication,2020 +P24597,INV-006135,to enable the optimization of anti-SARS-CoV-2 mAb candidates for developability and lowest cost of goods to produce a mAb product for the prevention of severe COVID-19 in vulnerable populations in low and middle income countries,N/A,,-99,"Just-Evotec Biologics, Inc.",1944053,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24598,INV-018301,to support the evidence generation and broad stakeholder use of African-based practitioner-led experiences in coping and mitigating the social and economic impacts of the COVID-19 pandemic on savings group women members,N/A,,-99,The Small Enterprise Education and Promotion Network,1028281,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P24599,INV-018693,to validate a point of care molecular test for SARS-CoV-2 and establish a plan for high capacity manufacturing to ensure affordability in LMICs,N/A,,-99,Alveo Technologies,700000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24600,INV-024783,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Xavier University of Louisiana,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24601,INV-024781,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,The Morehouse School of Medicine Inc.,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24602,INV-016832,to model the direct and indirect health and economic impacts of COVID-19 in LMICs,N/A,,-99,London School of Hygiene and Tropical Medicine,166059,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +P24603,INV-022092,"To develop, manufacture and conduct clinical testing of a novel nanoparticle displaying a SARS-CoV2 vaccine co-administered with a novel adjuvant.",N/A,,-99,"Icosavax, Inc.",9999899,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",,2020 +P24604,INV-024937,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Meharry Medical College,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24605,INV-024782,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Hampton University,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24606,INV-024733,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,Florida A&M University Foundation,1875000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24607,INV-005924,to support Covid response and maintain essential health services in Aspirational Districts,N/A,,-99,Piramal Swasthya,2000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Health Systems Research,Health service delivery,2020 +P24608,INV-023898,to increase access to COVID-19 testing at historically black colleges and universities (HBCUs) and their local communities in the US,N/A,,-99,The Howard University,1925000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P24609,INV-018944,"to understand how HIV and TB change the course of COVID-19 infection, and whether COVID-19 influences HIV and TB",N/A,,-99,Africa Health Research Institute NPC,4129787,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Africa,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Prognostic factors for disease severity | Supportive care, processes of care and management | Indirect health impacts",2020 +P24610,INV-022420,to inform strategies for engaging private healthcare providers in TB care and prevention by generating evidence on the extent to which healthcare markets in priority countries have been disrupted by the Covid pandemic,N/A,,-99,Research Institute of the McGill University Health Centre,1323642,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Economic impacts | Health financing,2020 +P24611,INV-023271,"to set up a migrant cell with Department of Rural Development, GoUP to support returning migrants and SHG women in accessing various government entitlements to mitigate adverse financial implication of COVID-19 pandemic",N/A,,-99,Project Concern International,599959,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Internally Displaced and Migrants | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24612,INV-023514,"to determine the overall, age and gender specific prevalence of SARS CoV-2 in the general population of Gauteng, following the peak of the COVID-19 outbreak",N/A,,-99,Wits Health Consortium (Pty) Ltd,1478702,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,Epidemiological studies,Disease surveillance & mapping,2020 +P24613,INV-018768,"to support Covid response by developing and implementing an Integrated Approach to strengthen containment, detection & treatment in Bangladesh",N/A,,-99,SAJIDA Foundation,321051,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,,,2020 +P24614,INV-019313,"To support African public health institutes to assess the impact and efficacy of various policy measures undertaken by African governments to respond to COVID-19, so as as to inform future responses to public health emergencies.",N/A,,-99,Makerere University School of Public Health,1332748,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24615,INV-022253,"to provide external technical assistance (TA) to the Government of Bangladesh as part of the Gates Foundation COVID-19 mitigation efforts, addressing both essential health services and COVID-19 response",N/A,,-99,ThinkWell Institute,1299362,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience",,2020 +P24616,INV-019524,to better understand how WECs are adapting to COVID-19 and help raise the voices of women and girls in the economic response efforts across 6 key African geographies,N/A,,-99,CARE,934135,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24617,INV-019155,to enable the identification of highly efficacious human anti-SARS-CoV-2 mAbs to protect the most vulnerable populations in low and middle income countries from severe COVID-19,N/A,,-99,Texas Biomedical Research Institute,2190000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24618,INV-024215,to support the COVID Response Fellowship program,N/A,,-99,Education Pioneers Inc.,1000000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24619,INV-021530,to help the government improve COVID-19 testing access by supporting the efforts of the national and state governments to overcome key challenges around testing scale-up,N/A,,-99,Clinton Health Access Initiative Inc,822885,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24621,INV-018728,to screen compounds in SARS2 infection model,N/A,,-99,University of Saskatchewan,10000,Unspecified,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Canada,,,,2020 +P24622,INV-022009,to undertake research on the impact of COVID policies on women workers in the informal sector to inform gender-responsive policies and strategies to empower women to recover and rebuild their livelihoods,N/A,,-99,International Center for Research on Women,1028039,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Gender,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24623,INV-022977,to support COVID-19 response in Indonesia,N/A,,-99,International Bank for Reconstruction and Development,600000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24624,INV-019081,to evaluate novel potentially protective vaccines to identify new candidate vaccines for future clinical testing for SARS-CoV-2 prevention,N/A,,-99,"Gritstone bio, Inc.",574923,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P24625,INV-019398,to build the capacity of government health officials to implement collaborative RCCE interventions to mitigate the spread of COVID-19 and future disease outbreaks,N/A,,-99,Search for Common Ground,985555,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2020 +P24626,INV-022699,to develop proof-of-concept methods for SARS-CoV-2 surveillance based on sewage and fecal sludge samples,N/A,,-99,University of Virginia,2165672,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24627,INV-022295,to characterize viological features of exhaled breath in a COVID-19 positive cohort,N/A,,-99,University of Maryland,400855,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P24628,INV-023750,"to determine the prevalence of maternal and fetal SARS'ÄêCoV'Äê2 infection in cases of fetal death in Mozambique, where the COVID'Äê19 pandemic is established",N/A,,-99,Instituto de Salud Global Barcelona,93250,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Europe,,,,,Spain,,Epidemiological studies,Disease surveillance & mapping,2020 +P24629,INV-006421,"to support the office of the President of Burkina Faso in rethinking, redesigning, and implementing its post Covide Economic recovery plan.",N/A,,-99,Tony Blair Institute for Global Change,600000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24630,INV-021263,to support Council of the Great City Schools member working groups develop tools and resources that can be broadly shared nationally for effective COVID-19 district reopening plans,N/A,,-99,Council of the Great City Schools,200006,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +P24631,INV-019121,to support China CDC to evaluate the quality of COVID-19 serological diagnostic reagents in China and provide evidence for scientific use of reagents in clinical diagnosis and epidemiological survey,N/A,,-99,"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention",71700,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,,,2020 +P24632,INV-022683,to ensure access to dexamethasone for treatment of severe COVID-19 disease in Africa,N/A,,-99,African Field Epidemiology Network,2202974,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,Health Systems Research,Health service delivery,2020 +P24633,INV-022816,to establish resources in LMICs for laboratory diagnosis of SARS-CoV-2,N/A,,-99,International Centre for Genetic Engineering and Biotechnology - Italy,438261,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Italy,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24634,INV-022251,"to summarize and curate evidence on the implementation, designs, and social/economic impacts of Covid-related social protection interventions with an emphasis on digitized cash transfers.",N/A,,-99,Innovations for Poverty Action,326317,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P24635,INV-018231,"to better position decision-makers/policymakers globally and in 10 priority countries to use evidence to adopt gender-responsive policies during COVID focusing on paid sick leave, child care, and inter-sectional discrimination",N/A,,-99,"University of California, Los Angeles",950000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Gender,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P24636,INV-018945,to understand disease severity and identify correlates of protection in human Sars-CoV-2 infection/Covid-19,N/A,,-99,Karolinska Institutet,99047,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Sweden,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +P24637,INV-022972,to support partners with data analyses around COVID-19 vaccines for low-resource settings,N/A,,-99,Linksbridge SPC,2323755,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United States of America,,"Vaccines research, development and implementation",,2020 +P24638,INV-021777,"to evaluate transmission dynamics of SARS-CoV-2 in Karachi, Pakistan",N/A,,-99,Aga Khan University,454499,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,Epidemiological studies,Disease transmission dynamics,2020 +P24639,INV-021518,to support laboratory and epidemiological response to COVID-19 in Nepal,N/A,,-99,Dhulikhel Hospital,249992,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Nepal,,,,2020 +P24640,INV-018044,to improve the availability and quality of evidence to inform gender-responsive policy and programming for the COVID-19 crisis with a focus on Kenya and Bangladesh,N/A,,-99,Innovations for Poverty Action,750944,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,Gender,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24641,INV-022413,"to fast track the development, production and equitable global access to safe, quality, effective and affordable COVID-19 diagnostics, therapeutics and vaccines so that lives can be spared and so that life can return to 'Äònormal'Äô",N/A,,-99,World Health Organization,1640000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,,,2020 +P24642,INV-018474,to research public discourse on vaccines in Germany and address possible implications for the global COVID-19 response,N/A,,-99,Institute for Strategic Dialogue US,199704,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Europe,,,,,United States of America,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2020 +P24643,INV-018586,to identify factors related to effective service delivery and experiences of care of maternal and newborn health services in Kenya during the COVID-19 pandemic,N/A,,-99,"University of California, Los Angeles",100000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P24644,INV-017880,to accelerate development of point-of-care tools and home-based ANC innovations to pilot decentralized ANC risk stratification during COVID-19,N/A,,-99,Ilara Health Ltd.,1120262,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24645,INV-019412,to test the feasibility of differentiated ANC provisions through primary clinics and home care innovations in mitigating the disruption of ANC services due to COVID-19,N/A,,-99,Safe Water & AIDS Project,754308,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24646,INV-021881,To provide technical assistance to the Department of Medical Education in UP to strengthen training of healthcare workers from L2 & L3 facilities on COVID-19,N/A,,-99,MAMTA HEALTH INSTITUTE FOR MOTHER AND CHILD,745054,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P24647,INV-005371,to provide clinical trial simulation services to improve the informativeness and efficiency of COVID-19 clinical studies,N/A,,-99,Mediana LLC,480000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Puerto Rico,,,,2020 +P24648,INV-023124,to characterize the virological features of a cohort of COVID-19 positive patients for improving diagnostic test deployment and understanding of transmission between children and adults,N/A,,-99,California Institute of Technology,1499983,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2020 +P24649,INV-022387,"to provide support to select slum communities in the city of Chennai, for reducing the spread of COVID-19 incidences, through Community Response Teams (CRTs)",N/A,,-99,Voluntary Health Services,273365,Human Populations,Unspecified,Unspecified,Other,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,,,2020 +P24650,INV-022287,to use models to project where COVID-19 cases are likely to be surging in the next 4-12 weeks in the United States and across the globe to best anticipate needs for future investment in therapeutics development,N/A,,-99,University of Washington Foundation,75000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24651,INV-017572,To support COVID-19 response in Bangladesh,N/A,,-99,International Bank for Reconstruction and Development,250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24652,INV-021539,to enhance clinical trial site capabilities for Quality Assurance/Quality Control systems in preparation of conducting phase 3 COVID-19 vaccine efficacy trials in LMIC,N/A,,-99,PATH,1500000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,,,,United States of America,,"Vaccines research, development and implementation",Phase 3 clinical trial,2020 +P24653,INV-021780,to characterize SARS-CoV-2 transmission dynamics and understand perceptions and opinions of those affected in an high density poor urban setting in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,881394,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Community engagement,2020 +P24654,INV-003687,to improve the supply of quality Chinese COVID-19 medical products to low and middle income countries through technical assistance to accelerate their World Health Organization Emergency Use Listing application process,N/A,,-99,World Health Organization,78178,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,Health Systems Research,"Medicines, vaccines & other technologies | Health leadership and governance",2020 +P24655,INV-017646,"to support service delivery by deploying a digital algorithm to triage and manage COVID-19 patients at primary health care facilities, and optimise date use",N/A,,-99,Terre des homes,746000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Digital Health,,,Switzerland,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P24656,INV-017644,"to support the Government of Burkina Faso in the planning, resource mobilization and partner engagement for an effective response to the COVID-19 epidemic in the country",N/A,,-99,Clinton Health Access Initiative Inc,300000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24657,INV-023152,to measure human monoclonal antibody interactions with hamster Fc gamma receptors to support preclinical studies for identification of human anti-SARS-CoV-2 monoclonal antibody product candidates,N/A,,-99,Rockefeller University,165872,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24658,INV-004537,to support solutions journalism in Nigeria and Kenya using initial coverage of responses to the COVID'Äê19 crisis to create a strong foundation for broad'Äêbased solutions reporting on a range of health and development issues,N/A,,-99,Solutions Journalism Network Inc,2614250,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24659,INV-017206,to develop and test low cost digital tools and at home testing for surveillance of COVID-19,N/A,,-99,University of California San Francisco,1931768,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Digital Health | Innovation,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24660,INV-017123,to impact public health by making clinical research data more accessible to research and development partners in order to reduce and prevent the spread of COVID-19,N/A,,-99,"Pharmaceutical Research Associates, Inc.",542321,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United States of America,,,,2020 +P24661,INV-017787,to support a workshop to increase stakeholder'Äôs awareness of global health and COVID-19 R&D importance and discuss prioritized R&D and clinical areas in the post-COVID-19 times,N/A,,-99,Shanghai Science and Technology Exchange Center,130000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,,,2020 +P24662,INV-021926,to rapidly collect and share bright spots with others in the field who are seeking models and strategies to address challenges for students with disabilities during COVID,N/A,,-99,University of Washington Foundation,22000,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts | Economic impacts,2020 +P24663,INV-019369,to support research designed to document the challenges and triumphs of the Historically Black Colleges and Universities (HBCUs) community in response to COVID-19,N/A,,-99,The Howard University,137428,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24664,INV-018724,to provide humanitarian relief to people affected by tropical storms in Central America while strengthening CRGR's staff and humanitarian teams in the context of COVID-19,N/A,,-99,PRO-VIDA,300000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,El Salvador,,,,2020 +P24665,INV-018824,to analyze and publish information about how state outcomes based funding and college promise policies are shifting as a result of COVID-19,N/A,,-99,Research for Action Inc,250000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24666,INV-021464,to enhance clinical trial site capabilities in preparation of conducting COVID-19 vaccine efficacy trials in LMIC,N/A,,-99,Instituto D'OR de Pesquisa e Ensino,1610000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Brazil,,"Vaccines research, development and implementation",,2020 +P24667,INV-018277,to provide COVID-19 sequencing support - in the form of procurement and distribution of key commodities - for a dozen African labs,N/A,,-99,Integrum Scientific LLC,393378,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24668,INV-018440,"to support the implementation of service delivery redesign in Kakamega County, and leverage the PROMPTS digital health platform to be a dynamic, direct-to-mother response tool that mitigates the indirect impacts of COVID-19",N/A,,-99,Jacaranda Health,3904954,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Digital Health,,,United States of America,,"Secondary impacts of disease, response & control measures",,2020 +P24669,INV-021581,to enhance clinical trial site capacity in preparation for conducting Phase 3 COVID-19 vaccine efficacy trials in low- and middle-income countries,N/A,,-99,International Vaccine Institute,1499050,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Korea,,"Vaccines research, development and implementation",Phase 3 clinical trial | Vaccine trial design and infrastructure,2020 +P24670,INV-021521,FIND proposes to deliver a multi-pronged COVID-19 diagnostic training program to support India'Äôs COVID-19 laboratory network through five different workstreams.,N/A,,-99,FIND,692527,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Switzerland,,,,2020 +P24671,INV-021256,to assemble and disseminate recommendations and resources on cross-sector strategies and tactics to connect and re-engage students due to disruptions caused by COVID-19,N/A,,-99,"National League of Cities, Institute for Youth, Education and Families",150000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24672,INV-021362,to support Lagos State's COVID 19 case management through the procurement and installation of up to 50 oxygen kiosks to rescue the high number of severe case of COVID 19 being recorded in health facilities,N/A,,-99,Clinton Health Access Initiative Inc,1419323,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Health Systems Research,Health service delivery,2020 +P24673,INV-019034,to scale up production of the adjuvant CpG1018 to support the global COVID19 response,N/A,,-99,Dynavax Technologies Corporation,1200000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2020 +P24674,INV-005081,"to provide evidence, based on existing data and modeling, on the link between sanitation and public health, including the link between hygiene and COVID-19 infections.",N/A,,-99,University of Michigan,472118,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures,2020 +P24675,INV-017541,to support the Government of Uganda to expand its testing capabilities to meet the need for COVID-19 case finding and strengthen contact tracing,N/A,,-99,United Nations Development Programme,357179,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2020 +P24676,INV-022057,to support rapid synthesis of data on COVID-19 in pregnancy,N/A,,-99,The George Washington University,437641,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24677,INV-018716,"to support the development and implementation of actions that promote exchange, sharing, learning and coordination of COVID-19 related topics, among the Global South actors and also with the Global North",N/A,,-99,African Development Solutions (Adeso),291200,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Kenya,,,,2020 +P24678,INV-018007,to improve measurement of gender dimensions of the COVID crisis in surveys and studies,N/A,,-99,University of California San Diego,801915,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Gender,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24679,INV-018718,to increase our understanding of covid-19,N/A,,-99,Icahn School of Medicine at Mount Sinai,10000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24680,INV-006232,to seek treatments for COVID-19 as part of the foundation's emergency response efforts,N/A,,-99,University of North Carolina at Chapel Hill,280501,Unspecified,Unspecified,,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24681,INV-017895,to increase our understanding of covid-19,N/A,,-99,"SomaLogic, Inc",10000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24682,INV-017872,to accelerate the development and launch of critical Rapid Diagnostic Tests for the detection of COVID-19 infection in order to control the current global pandemic,N/A,,-99,E25Bio Inc,500000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24683,INV-018221,to provide ex-ante modeling and other data analysis to inform the identification of policies and public investments for addressing covid-19 related impacts on inclusive agricultural transformation,N/A,,-99,International Food Policy Research Institute,2400471,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P24684,INV-015752,to support evaluation of client outcomes in COVID-driven permanent supportive housing interventions in King County,N/A,,-99,University of Washington Foundation,20000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24685,INV-021500,"to evaluate the safety, immunogenicity, and potential efficacy of a candidate vaccine to prevent COVID-19 infection and/or disease in the South African population",N/A,,-99,"Novavax, Inc.",15000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase),2020 +P24686,INV-019229,to develop a machine learning approach to discover new combinations of drugs against Covid,N/A,,-99,Relation Therapeutics,1333586,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",,2020 +P24687,INV-018493,to support the African Medical Devices Forum technical working groups develop and offer scientific options on use of emerging COVID-19 diagnostics and other products to African countries,N/A,,-99,African Union Development Agency - New Partnership for Africa'Äôs Development,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2020 +P24688,INV-018138,"to describe the histopathology and immune response in fatal COVID-19 cases in Malawi, thereby generating knowledge that may inform effective immunomodulatory treatments",N/A,,-99,University of Glasgow,685373,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Clinical characterisation and management | Pathogen: natural history, transmission and diagnostics",Disease pathogenesis | Immunity,2020 +P24689,INV-022292,provided communication and dissemination support for the University of Florida research about the district COVID-19 response.,N/A,,-99,Impact Florida Inc,94608,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24690,INV-017659,to support citizen in a communications and advocacy campaign to reform the health systems in West Africa following the COVID-19 outbreak,N/A,,-99,West Africa Think Tank (WATHI),150000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Senegal,,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement,2020 +P24691,INV-021412,to develop and compare methods for SARS-CoV-2 surveillance based on sewage and fecal sludge samples,N/A,,-99,The Water Research Foundation,247348,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24692,INV-018918,"to examine the virtual learning experiences of middle and high school students during COVID-19 closures and design change ideas to test in virtual, hybrid, or re-entry settings during the 2020-2021 school year",N/A,,-99,Community Design Partners,148800,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Social impacts,2020 +P24693,INV-018673,to create and disseminate social and behaviour change communication on Covid-19 issues in Bihar,N/A,,-99,Project Concern International,249873,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24694,INV-018055,to plan for how to produce more equitable value for students in response to COVID-19 challenges,N/A,,-99,Arizona State University Foundation for A New American University,500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24695,INV-018067,to aid countries responding to COVID-19 with coordinated data and modeling support,N/A,,-99,Columbia University,5000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24696,INV-016635,to evaluate the potential efficacy of a Ribonucleic acid (RNA) vaccine against COVID-19,N/A,,-99,Imperial College London,1080771,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Vaccines research, development and implementation",,2020 +P24697,INV-017285,to support rapid provision of excellent digital mathematics content in response to school closures related to COVID-19,N/A,,-99,Zearn,800259,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24698,INV-016078,"to provide data on epidemiology and seasonality of infant low birthweight, and detect indirect effects of the COVID-19 outbreak on MNCH outcomes in Haydom, Tanzania",N/A,,-99,University of Virginia,77149,Unspecified,Unspecified,Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24699,INV-018455,to evaluate the signs and symptoms of COVID-19 in a data-consortium approach to inform better clinical decision making for diagnosis,N/A,,-99,Sage Bionetworks,1902558,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing,,,United States of America,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +P24700,INV-018861,"to further our understanding of how different defined audiences perceive economic mobility in the United States, including how those views are impacted by COVID-19",N/A,,-99,Harmony Labs Inc,212055,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24701,INV-019182,"To optimize the performance of a novel instrument-free, point-of-care molecular diagnostic test for SARS-CoV-2",N/A,,-99,Biology Works LLC,99274,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24702,INV-017113,to maintain a public database on school/district responses to COVID-19 and create knowledge products that capture learning from these data.,N/A,,-99,University of Washington Foundation,418911,Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24703,INV-019257,to understand the comparative effectiveness of treatments for covid-19,N/A,,-99,University of Oxford,10000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",,2020 +P24704,INV-018464,to surface immunization best practices and innovations in the field and related service delivery insights in response to COVID-19,N/A,,-99,The Geneva Learning Foundation,287500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Approaches to public health interventions,2020 +P24705,INV-019301,to support schools in Texas to plan and respond to student learning that was lost due to the COVID-19 crisis,N/A,,-99,Educate Texas,1091441,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24706,INV-017654,to support increased African research & development capacity to fight the Covid-19 pandemic in Africa,N/A,,-99,African Academy of Sciences,730373,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,,,2020 +P24707,INV-017543,to support the Economic Task Force of the Rwandan government to ensure an effective response to COVID-19 across recovery and normalization phases,N/A,,-99,Rwanda Biomedical Centre,500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Rwanda,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24708,INV-017968,to provide resources necessary as charter public schools in Washington State adjust timelines and structures in response to COVID-19 impacts,N/A,,-99,Washington State Charter Schools Association,2275499,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24709,INV-018569,to develop an assay that could be used to enable rapid quantification of SARS-CoV-2 pathogens in wastewater,N/A,,-99,California Institute of Technology,388502,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24710,INV-017597,to provide communication support to Uttar Pradesh (UP) and Bihar on Covid-19 response,N/A,,-99,Centre for Advocacy and Research,199995,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Policies for public health, disease control & community resilience",Communication,2020 +P24711,INV-019026,to provide support for charter school leaders of color to address COVID-19 in their schools and to provide nonpartisan information to thought leaders and federal policymakers,N/A,,-99,National Alliance for Public Charter Schools,200000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24712,INV-017330,"to provide timely, optimized dosing recommendations of re-purposed and new medications to combat COVID-19",N/A,,-99,University of California San Francisco,125174,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P24713,INV-018394,to strengthen emergency preparedness and management systems of the Government of Bihar for managing the COVID-19 crisis so that impacts of at-risk communities would be minimized,N/A,,-99,Asian Disaster Preparedness Center,285149,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Thailand,,"Secondary impacts of disease, response & control measures | Health Systems Research",Health leadership and governance,2020 +P24714,INV-021239,to develop a Covid-19 vaccine candidate that could be produced using the existing influenza virus vaccine manufacturing facilities,N/A,,-99,PATH,615250,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Vaccines research, development and implementation",,2020 +P24715,INV-005598,to understand the causal factors behind UHC progress in three Asian countries and to identify Asian countries (and underlying factors) that have responded effectively to COVID,N/A,,-99,National University of Singapore,1586847,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Singapore,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +P24716,INV-017300,"To provide near-term and ongoing research, analysis and policy guidance on the gendered risks, impact & response related to the COVID-19 pandemic in LMICs using qualitative and quantitative data",N/A,,-99,Simon Fraser University,1638614,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,Data Management and Data Sharing | Gender,,,Canada,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease susceptibility,2020 +P24717,INV-018629,to evaluate the use of a digital health platform to make care for COVID more accessible to marginalized populations,N/A,,-99,Drexel University,496783,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Digital Health,,,United States of America,,Health Systems Research,Health service delivery,2020 +P24718,INV-019400,to assess whether malaria infection affects the clinical course of COVID-19 in Kenya and Burkina Faso,N/A,,-99,London School of Hygiene and Tropical Medicine,1824643,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Europe,,,,,United Kingdom,,Clinical characterisation and management,Disease pathogenesis,2020 +P24719,INV-016945,"to enable the World Bank to support the efforts of Government of India to deal with the health, economic and social consequences of the Covid 19 emergency",N/A,,-99,International Bank for Reconstruction and Development,500000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +P24720,INV-017556,to enhance capacity of COVID-19 RT-PCR diagnostic testing and to inform interventions to slow transmission in Bangladesh,N/A,,-99,"International Centre for Diarrhoeal Disease Research, Bangladesh",1280094,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24721,INV-017174,to support Nigeria's COVID-19 Emergency Response Systems Readiness for case management,N/A,,-99,Clinton Health Access Initiative Inc,1499741,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24722,INV-018479,to test the ReFrame library in human lung cell line infected with SARS2,N/A,,-99,University of Pennsylvania,1246352,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +P24723,INV-018021,"to assess the impact of COVID-19 on measles incidence and deaths, including delays or cancellations of SIAs (both reactive and planned) and decreases in routine MCV coverage",N/A,,-99,Penn State,83619,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24724,INV-017532,to provide technical and decision support to the East African Community Secretariat to minimize the impact of the COVID-19 pandemic in the region,N/A,,-99,African Economic Research Consortium,650000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,"Secondary impacts of disease, response & control measures",,2020 +P24725,INV-017547,to support the development of serologic assays within a scaled laboratory network for detection of SARS-CoV-2 in specific populations in Kenya for decision-making,N/A,,-99,University of Oxford,466975,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24726,INV-017568,to support COVID-19 response in Bangladesh,N/A,,-99,United Nations Development Programme Bangladesh,1725277,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,,,2020 +P24727,INV-019225,to provide a co-branded (CCSSO and CFC) set of comprehensive COVID-19 state education reopening plans that address health and safety guidance at both the SEA and LEA levels,N/A,,-99,Chiefs for Change,1600000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24728,INV-018030,"to fund core lab capacity to conduct next-generation sequencing, data analysis, and visualization on SARS-CoV-2 in the DRC",N/A,,-99,University of Nebraska Medical Center,95758,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24729,INV-018560,to evaluate pre-exposure prophylactic measures against COVID-19 disease,N/A,,-99,Henry Ford Health System,300000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Clinical characterisation and management | Infection prevention and control,"Supportive care, processes of care and management",2020 +P24730,INV-019449,to gain deeper understanding of the mechanisms by which SARS-CoV-2 causes disease,N/A,,-99,Johns Hopkins University School of Medicine,150000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P24731,INV-017035,to assess the impact of COVID-19 on pregnancy and newborn health in the US and rapidly share the data with global partners,N/A,,-99,University of California San Francisco,1000000,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24732,INV-017520,to identify factors that can reduce the risk of contracting COVID-19 by health care workers in resource constrained settings.,N/A,,-99,Certara USA Inc,1254000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,Unspecified,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease susceptibility,2020 +P24733,INV-018812,to support repurposing drugs to the treatment of COVID-19,N/A,,-99,"Calibr, a division of The Scripps Research Institute",10000,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P24734,INV-016702,to support the creation and convening of a policy forum 'Äì managed by key trusted partners and grantees 'Äì to flexibly outline critical issues and craft a series of state and federal policy recommendations related to COVID-19,N/A,,-99,New America,1050000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24735,INV-017789,to support non-governmental organizations and social enterprises/ organizations to catalyze or scale-up COVID-19 innovations,N/A,,-99,United Way Worldwide,1268125,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24736,INV-019009,"to support the New York City Department of Education in leveraging strategic partnerships to successfully recover from COVID-19, reopen schools, and re-engage students during the 2020-2021 school year",N/A,,-99,Fund for Public Schools Inc,500029,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24737,INV-017985,to assess whether malaria infection affects the clinical course of COVID-19 in Kenya,N/A,,-99,Liverpool School of Tropical Medicine,2571330,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Europe,,,,,United Kingdom,,Clinical characterisation and management,Disease pathogenesis,2020 +P24738,INV-017245,to establish virtual training modules for laboratory and data analytics work related to COVID-19 genomic epidemiology,N/A,,-99,MRIGlobal,249836,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P24740,INV-018365,to support schools in Tennessee to plan and respond to student learning that was lost due to the COVID-19 crisis,N/A,,-99,Tennessee State Collaborative on Reforming Education,1073000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24741,INV-018148,"to investigate the epidemiology of SARS-CoV-2 infection among health care workers who triage patients and provide care to COVID-19 patients, and laboratory personnel who test clinical samples for SARS-CoV-2 infection",N/A,,-99,Wits Health Consortium (Pty) Ltd,1140129,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,Epidemiological studies,Disease susceptibility,2020 +P24742,INV-018459,to support schools in Florida to plan and respond to student learning that was lost due to the COVID-19 crisis,N/A,,-99,Impact Florida Inc,1042865,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24743,INV-018875,to create a webinar series and practice brief that surfaces key actions and lessons that help system leaders use improvement methods to respond to the educational crisis precipitated by COVID-19,N/A,,-99,Carnegie Foundation for the Advancement of Teaching,99500,Other,Not applicable,Unspecified,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24744,INV-017072,to strengthen risk communications and community engagement within the global COVID-19 response,N/A,,-99,International Federation of Red Cross and Red Crescent Societies,1478125,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,Switzerland,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +P24745,INV-017710,to evaluate the safety and immune responses elicited by a candidate COVID-19 vaccine in the South African population including but not limited to individuals living with HIV,N/A,,-99,Wits Health Consortium (Pty) Ltd,13687347,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Clinical trial (unspecified trial phase),2020 +P24746,INV-017909,"to expand the availability of gender disaggregated data for COVID, review the evidence on what works for gender responsive policymaking for the crisis, and advocate for improved gender-intentional responses and policymaking",N/A,,-99,UCL Consultants Limited,706871,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Data Management and Data Sharing | Gender,,,United Kingdom,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24747,INV-017889,to explore innovative mechanisms to link 'harder to reach' workers to services and benefits valuable during the current COVID crisis,N/A,,-99,"National Domestic Workers Alliance, Inc.",330000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24749,INV-017431,to research the impact of emergency aid in contributing to the success of the most vulnerable post-secondary students during the COVID-19 pandemic and resulting economic crisis,N/A,,-99,Temple University - Of The Commonwealth System of Higher Education,499828,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P24750,INV-017221,to collect data to estimate the burden of COVID-19 in pregnancy; outcomes associated with COVID-19 in pregnancy and describe maternal and newborn morbidities associated with COVID-19 in Western Kenya,N/A,,-99,HJF Medical Research International Inc.,1482400,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2020 +P24751,INV-017356,to generate a machine learning framework to answer researchers and decision makers questions related to COVID-19 symptoms and tracking mitigation,N/A,,-99,SYSTEM INC,240000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures,2020 +P24752,INV-006124,to train and test machine learning approaches for understanding and informing the response to the COVID-19 crisis in Africa,N/A,,-99,"Macro-Eyes, Inc.",711349,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Innovation,,,United States of America,,Epidemiological studies,Impact/ effectiveness of control measures,2020 +P24753,INV-018054,to plan for how to produce more equitable value for students in response to COVID-19 challenges,N/A,,-99,WGU Advancement,500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24754,INV-017592,Structure-guided stabilization of the SARS-CoV-2 spike protein for vaccines and diagnostics.,N/A,,-99,University of Texas at Austin,100000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2020 +P24755,INV-017376,to provide coordinated support to relief measures in the light of COVID 19,N/A,,-99,PRADAN,300000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,,,2020 +P24756,INV-017601,"to support the coordination and mobilization of civil society's response to COVID-19 to mitigate community transmission and minimize the health, social and economic impact at the subnational and community level",N/A,,-99,Health Systems Consult Limited,117246,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +P24757,INV-017282,to study the effects of COVID-19 on mother and newborn outcomes in an established pregnancy cohort study in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,1999889,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24758,INV-017574,to strengthen risk communications and community engagement within the global COVID-19 response,N/A,,-99,World Health Organization,562284,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,Switzerland,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +P24759,INV-016638,to establish human organ chip model in BSL3 lab to assess potential Covid19 therapeutics,N/A,,-99,"University of Maryland, Baltimore",194465,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P24761,INV-017273,"to study the effects of COVID-19 on maternal, newborn, and child health outcomes in an established network of pregnancy cohort studies",N/A,,-99,World Health Organization,1999023,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24762,INV-018309,to support planning for resilient schools in light of the COVID-19 event,N/A,,-99,Council of Chief State School Officers,775000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24763,INV-017863,to support Networks for School Improvement and their school partners with student progress monitoring and reporting in response to COVID-19 related changes,N/A,,-99,"Education Analytics, Inc.",999167,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24764,INV-017424,"to mitigate the indirect impact of COVID-19 on essential health services for pregnant mothers, newborns, children, adolescents and older adults",N/A,,-99,World Health Organization,4999303,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Newborns (birth to 1 month) | Older adults (65 and older),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24765,INV-017593,to strengthen risk communications and community engagement within the global COVID-19 response,N/A,,-99,United States Fund for UNICEF,1412100,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +P24766,INV-018984,to support the work of Choose Love during the Covid-19 pandemic,N/A,,-99,Choose Love Inc,10000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24767,INV-018915,"to conduct a rapid assessment of recent mortalities in Addis Ababa to examine whether or not the very low level of COVID-19 related mortalities registered so far (May 18, 2020) is mostly due to undetected cases",N/A,,-99,"MERQ Consultancy, PLC",321081,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ethiopia,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2020 +P24768,INV-017319,"to provide timely, optimized dosing recommendations of re-purposed and new medications to combat COVID-19",N/A,,-99,University of Oxford,931,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P24769,INV-006377,"To support developing assays platform of drug screening and subunit vaccines of coronavirus, which will contribute to product innovation of COVID-19 pandemic control",N/A,,-99,"Institute of Microbiology, Chinese Academy of Sciences",359820,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2020 +P24770,INV-017529,to support the University of Nairobi data and analytics collaboration with their response to the COVID-19 emergency and strengthening of health data analytics,N/A,,-99,University of Nairobi,500010,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Kenya,,,,2020 +P24771,INV-017651,to seek treatments for COVID-19 as part of the foundation's emergency response efforts,N/A,,-99,Vanderbilt University Medical Center,203500,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24772,INV-017101,to support the National Academies of Sciences and Council of State Science Supervisors in coordinating NGSS professional learning needs in light of COVID-19,N/A,,-99,"The National Academies of Sciences, Engineering, and Medicine",10000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24773,INV-017402,to provide technical assistance to hygiene behavior change interventions to reduce the spread of COVID-19 in low and middle income countries.,N/A,,-99,London School of Hygiene and Tropical Medicine,716517,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Research on Capacity Strengthening",Approaches to public health interventions | Systemic/environmental components of capacity strengthening,2020 +P24774,INV-017275,"to support COVID-19 Emergency Response Systems Readiness in Kaduna State, Nigeria",N/A,,-99,Kaduna State Primary Health Care Board,100000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,,,2020 +P24775,INV-017588,to reduce the impact of COVID-19 on the most vulnerable populations in South Africa through innovative delivery solutions of essential products and services,N/A,,-99,Percept Actuaries and Consultants,634296,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24776,INV-017335,"to provide timely, optimized dosing recommendations of re-purposed and new medications to combat COVID-19.",N/A,,-99,Institut National de la Sant√© et de la Recherche M√©dicale,435,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2020 +P24777,INV-016575,to enable access to samples from COVID-19 patients to support mAb discovery and identification of correlates of natural protection/disease severity.,N/A,,-99,University of Washington Foundation,95000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P24778,INV-017443,"to support the Government of Nigeria and the Presidential Task Force with rapid access to Epi, Surveillance and modeling information for rapid decision making in response to COVID-19",N/A,,-99,University College London,340000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,Epidemiological studies,,2020 +P24779,INV-017587,This grant will be used to operationalize validated COVID rapid diagnostic testing and sample self- collection in South Africa,N/A,,-99,Wits Health Consortium (Pty) Ltd,850000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,,,2020 +P24780,INV-005925,to explore and deepen philanthropic network for COVID and other health and developmental needs in Tier 2 and 3 cities in UP and Bihar,N/A,,-99,Asian Venture Philanthropy Network Limited,466292,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Singapore,,Health Systems Research,Health leadership and governance,2020 +P24781,INV-017791,"to contribute to India Covid Response Fund, which will deploy resources towards disease spread prevention, healthcare delivery and system capacity, humanitarian needs and socioeconomic support areas",N/A,,-99,GiveIndia,970000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Social impacts | Economic impacts | Other secondary impacts | Health service delivery,2020 +P24782,INV-017737,to provide deep characterization of a cohort of COVID-19-positive patients and insights into the virological and immunological features,N/A,,-99,Stanford University,100000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Disease pathogenesis",2020 +P24783,INV-018240,to assess the performance of a novel tongue swab for detection of COVID and TB from the same specimen,N/A,,-99,University of Washington Foundation,50000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24784,INV-017995,to evaluate the efficacy of concentrated convalescent plasma enriched for anti-S IgG in high-risk elderly people post-exposure to SARS-CoV2,N/A,,-99,Fundaci√≥n INFANT,534332,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Argentina,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P24785,INV-018056,to plan for how to produce more equitable value for students in response to COVID-19 challenges,N/A,,-99,Southern New Hampshire University,491899,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24786,INV-016600,to support improved access to respiratory care equipment as part of a COVID-19 response in low- and middle-income countries,N/A,,-99,PATH,12500000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Clinical characterisation and management,,2020 +P24787,INV-017492,to contribute to the Uganda Ministry of Health COVID response through a catalytic partnership with the private sector,N/A,,-99,Clinton Health Access Initiative Inc,100000,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24788,INV-017846,to support availability of awareness of resources that support students with disabilities during distance learning due to COVID-19,N/A,,-99,"Friends of Brooklyn Laboratory Charter Schools, Inc.",50000,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24789,INV-017216,to strengthen capacity of health workers in response to COVID 19,N/A,,-99,World Health Organization India Country Office,239718,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Clinical characterisation and management,,2020 +P24790,INV-018408,to support the planning and implementation of summer youth programming and COVID learning loss recovery for students in NYC to prepare them for a successful start of school,N/A,,-99,The Children's Aid Society,1000000,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24791,INV-017287,"develop instructional videos, a pacing guide, and virtual professional learning tools for adapting Illustrative Mathematics to address expecting learning gaps due to COVID-19.",N/A,,-99,Illustrative Mathematics,1030000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24792,INV-017613,"to accelerate Kano State's response to COVID-19 through increasing efficiencies in delivering test samples to laboratories, strengthening surveillance, and providing additional expertise to the State Task Force",N/A,,-99,Kano State Government,199823,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Nigeria,,Health Systems Research,Health service delivery,2020 +P24794,INV-017215,to develop a digital biomarker of COVID-19 and understand an individual'Äôs susceptibility to infection and cascading effects of disease,N/A,,-99,Evidation Health Inc,242000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis,2020 +P24795,INV-016047,to conduct infection prevention and control (IPC) trainings tailored to the COVID-19 response,N/A,,-99,All India Institute of Medical Sciences,361086,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Infection prevention and control,,2020 +P24796,INV-006379,to support optimizing pseudovirus platforms for COVID-19 product innovation,N/A,,-99,National Institutes for Food and Drug Control,208575,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Innovation,,,China,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24797,INV-018037,to support the United Nations'Äô response to the ongoing COVID-19 pandemic,N/A,,-99,Clinton Health Access Initiative Inc,632500,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24798,INV-017881,to provide support to Crisis Text Line during the Covid-19 Pandemic,N/A,,-99,Crisis Text Line Inc.,25000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24799,INV-017840,to support availability of awareness of resources that support students with disabilities during distance learning due to COVID-19,N/A,,-99,InnovateEDU,50000,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24800,INV-017306,to support animated storytelling for Global COVID-19 prevention,N/A,,-99,Stanford University,245000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24801,INV-017499,to conduct a clinical study evaluating the efficacy of re-purposed drugs to prevent COVID-19 infection in health care workers in Sub-Saharan Africa,N/A,,-99,Washington University,4425000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P24802,INV-017821,to support availability of awareness of resources that support students with disabilities during distance learning due to COVID-19,N/A,,-99,The National Center for Special Education in Charter Schools Inc.,50000,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24803,INV-017217,to develop a COVID-19 vaccine,N/A,,-99,Karolinska Institutet,353081,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Sweden,,"Vaccines research, development and implementation",,2020 +P24804,INV-006462,to develop a COVID-19 vaccine that can be produced in large amounts at low cost to meet the pandemic-response needs of low- and middle-income countries,N/A,,-99,"SK bioscience Co., Ltd.",3600000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Korea,,"Vaccines research, development and implementation",,2020 +P24805,INV-018261,"to catalog some of the most important lessons learned from past economic disasters and recovery efforts, in order to guide our thinking on what can be done now in response to the COVID-19 pandemic",N/A,,-99,Ohio State University,42363,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24806,INV-017595,To strengthen and support the Uttar Pradesh Government's multi-pronged plan for containment and treatment of COVID-19,N/A,,-99,Transforming Rural India Foundation,5000004,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,Health Systems Research,Health leadership and governance,2020 +P24807,INV-016831,to develop a low cost and high-throughput method for COVID molecular testing to expand testing capacity,N/A,,-99,Quantigen LLC,8443915,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24808,INV-018160,to provide project management support to the WHO AFRO AVAREF program so that they can implement their revised procedure for clinical trial application review as efficiently as possible given the influx of COVID related applications expected,N/A,,-99,Wits Health Consortium (Pty) Ltd,613002,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",,2020 +P24809,INV-006445,to support research and development for COVID-19 response,N/A,,-99,"Shanghai Zerun Biotechnology Co., Ltd.",1000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,,,2020 +P24810,INV-017383,to provide technical assistance to local actors across Asian Preparedness Partnership countries who are at the forefront of COVID -19 preparedness and response activities,N/A,,-99,Asian Disaster Preparedness Center,450044,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Thailand,,,,2020 +P24811,INV-018043,"to provide effective, accessible, scalable treatment for covid-19",N/A,,-99,Institut de Cardiologie de Montr√©al,3300000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Canada,,"Therapeutics research, development and implementation",,2020 +P24812,INV-017380,To facilitate the early development of a new COVID antigen detection assay,N/A,,-99,Harvard University,205717,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24813,INV-004839,to support development of a surveillance system for maternal newborn and child health in Malawi during the COVID-19 epidemic,N/A,,-99,University of Liverpool,295186,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Women | Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,,,2020 +P24814,INV-017812,"to capture and package lessons learned, templates, toolkits, etc. from the Seattle Foundation COVID-19 Response Fund as a model for other emergency response funds around the country",N/A,,-99,Seattle Foundation,150000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24815,INV-017647,to improve postsecondary transitions in response to the disruption of education due to the COVID-19 outbreak,N/A,,-99,Education Commission of the States,446841,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24816,INV-017075,to consider how Edtech can mitigate the impact of COVID-19 and support equitable education access and learning,N/A,,-99,ODI,499999,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24817,INV-017728,"to support the Democratic Republic of the Congo Emergency Operations Center to effectively respond to COVID-19 and associated health threats, including malaria resurgence",N/A,,-99,PATH,1871026,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24818,INV-017847,to build the capacity of funders to manage US-centric COVID-19 emergency funds effectively and efficiently.,N/A,,-99,United Philanthropy Forum,10208917,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,Research on Capacity Strengthening,Cross-cutting,2020 +P24819,INV-017269,to support volunteer opportunities during COVID-19,N/A,,-99,VolunteerMatch,1201918,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Volunteers,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24820,INV-017637,to develop an inexpensive and high-throughput manufacturing and packaging system for the production of nasal swabs which are required for SARS-CoV-2 testing,N/A,,-99,SteriPack (USA) Limited,852000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",,2020 +P24821,INV-017777,"to support Lagos State's Strategic Communication Initiative to combat COVID 19 Stigma and increase early reporting through the state's "" Creatives"" Project",N/A,,-99,Clinton Health Access Initiative Inc,100000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24822,INV-017800,to support grassroots givers in their response to COVID-19,N/A,,-99,DonorsChoose,1000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24823,INV-017861,to develop and implement a rapid response for COVID-preparedness and COVID-management in the aspirational districts,N/A,,-99,Transforming Rural India Foundation,456580,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,India,,"Infection prevention and control | Policies for public health, disease control & community resilience",,2020 +P24824,INV-017746,"to provide a lifesaving respiratory support bundle to Ethiopia-based health centers in anticipation of COVID-related needs, including procurement, local production, and asset/inventory tracking",N/A,,-99,Clinton Health Access Initiative Inc,1638487,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24825,INV-017302,to evaluate the potential of the Bacillus Calmette-Gu√©rin vaccine to protect against COVID-19 disease and to further understanding of how Bacillus Calmette-Gu√©rin affects the human immune system,N/A,,-99,Murdoch Childrens Research Institute,13425562,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Australia,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity,2020 +P24826,INV-017614,to support the Nigeria government through the Nigeria Center for Disease Control to improve its testing capacity for COVID-19 pandemic,N/A,,-99,eHealth Africa,300533,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24827,INV-017776,to conduct an independent analysis of contact tracing tools that can be used for COVID-19 disease surveillance in developing countries,N/A,,-99,Johns Hopkins University Bloomberg School of Public Health,48962,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease transmission dynamics,2020 +P24828,INV-017355,to support availability and awareness of resources that support students with disabilities during distance learning due to COVID-19,N/A,,-99,National Center for Learning Disabilities,75000,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24829,INV-017660,to support Ethiopia's response to the COVID-19 pandemic by leveraging public private partnerships to ramp up and strengthen capacity for testing and diagnostics,N/A,,-99,Medpharm Holdings Africa,1098930,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Ethiopia,,,,2020 +P24830,INV-016640,To provide clinical trial supply service to accelerate the development of therapeutic drugs to combat COVID-19,N/A,,-99,Almac Clinical Services LLC,288933,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +P24831,INV-016641,"to leverage existing funded platforms for integration of COVID-19 research relevant to pregnant women, infants and young children in Mali.",N/A,,-99,"University of Maryland, Baltimore",1491427,Unspecified,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24832,INV-017820,"to provide remote training and mentoring of bedside respiratory support care for COVID patients in Pakistan and beyond via videoconferencing with off-site, expert clinicians",N/A,,-99,Aga Khan University,499756,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P24833,INV-017272,to support maternal and newborn care and document lessons in Kenya during the COVID-19 pandemic,N/A,,-99,Aga Khan University,99890,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Pakistan,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P24834,INV-016651,to evaluate the utility of digital biomarkers to evaluate frontline health workers stress and recovery in the COVID epidemic,N/A,,-99,4YouandMe,276576,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Digital Health,,,United States of America,,Clinical characterisation and management,Prognostic factors for disease severity,2020 +P24835,INV-016942,"to collect survey data on the economic and professional impacts of the COVID-19 outbreak on low-income, hourly workers across the United States",N/A,,-99,Harvard University,330660,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24836,INV-016631,to test the efficacy of inhaled pulmonary surfactant replacement therapy in adults with COVID-19 disease,N/A,,-99,The University of Southampton,1648270,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2020 +P24837,INV-017754,to provide technical assistance to WA Dept of Health that will drive and sustain further reductions in community COVID-19 transmission and allow removal of physical distancing measures,N/A,,-99,PATH,398668,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Infection prevention and control,,2020 +P24838,INV-017438,to provide early thoughts to state and district leaders on forthcoming K12 financial decisions in a post-COVID world,N/A,,-99,Georgetown University,90000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24839,INV-017670,to support Ethiopia's response to the COVID-19 pandemic by prototyping the optimum digital health information system to facilitate rapid operationalization of public-private collaboration to conduct testing and follow-up in Addis Ababa,N/A,,-99,"JSI Research & Training Institute, Inc.",799972,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,Digital Health,,,United States of America,,,,2020 +P24840,INV-015957,"to harness gender for vector control programs to eliminate diseases such as Zika by conducting fieldwork in Brazil and analyzing existing data from Tanzania to determine how women impact these programs, and how they are affected by them",N/A,,-99,London School of Economics and Political Science,100000,Human Populations,Unspecified,Unspecified,Unspecified,Women | Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,Gender,,,United Kingdom,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience",Vector control strategies | Approaches to public health interventions | Community engagement,2020 +P24841,INV-017814,to support COVID-19 response efforts in Washington State,N/A,,-99,Washington State Department of Health,260000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24842,INV-016894,"to understand prevalence and outcomes of COVID-19 in children and their adult contacts, and healthcare workers in low-resource settings",N/A,,-99,University of Washington Foundation,1375331,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2020 +P24843,INV-016823,"to improve our understanding of Covid-19, which will inform the development of medicines to treat the disease",N/A,,-99,University of Washington Foundation,100000,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P24844,INV-017657,to support COVID-19 response in Ethiopia by addressing gaps at quarantine and isolation centers to ensure that health and safety needs of this high risk population and those of the front line health care workers serving them is met,N/A,,-99,American International Health Alliance,1000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Infection prevention and control,IPC in health care settings,2020 +P24845,INV-017621,to provide COVID-19 response support in Ethiopia with a focus on supporting health systems strengthening approaches that can prevent the adverse effects pandemics have on routine essential services such as maternal and newborn health,N/A,,-99,"JSI Research & Training Institute, Inc.",1100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P24846,INV-016776,"to support the global COVID-19 outbreak response by testing of selected compounds in the 3D in vitro human respiratory tissues, MucilAir'Ñ¢",N/A,,-99,Epithelix S√†rl,1767102,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24847,INV-016128,"to screen for potential therapeutics against low passage patient-isolate of the current pandemic coronavirus (SARS-CoV-2, England2)",N/A,,-99,University of Glasgow,269898,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24848,INV-016943,to address important questions regarding the vertical transmission of COVID-19 virus and the transfer of maternal immunity through breastmilk,N/A,,-99,University of Idaho,315048,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +P24849,INV-016821,"to develop a repository of essential diagnostics reagents, and to evaluate diagnostics tools for the novel SARS-CoV-2 virus",N/A,,-99,PATH,4271768,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24850,INV-016608,to support improved and efficient strategic coordination for Nigeria's emergency response to COVID-19 outbreak,N/A,,-99,Tony Blair Institute for Global Change,200000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,,,2020 +P24851,INV-017748,to plan for creation of equitable value for postsecondary students in response to COVID-19 challenges,N/A,,-99,WGU Advancement,100000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24852,INV-017439,to provide early thoughts to district and school leaders on how to make resource allocation decisions in a post-COVID era,N/A,,-99,"Education Resource Strategies, Inc.",100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P24853,INV-017440,to provide early thoughts to state leaders on K12 resource allocation in a post-COVID era,N/A,,-99,Foundation for Excellence in Education,100000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24854,INV-017205,"to develop and assess novel diagnostic tests for SARS-CoV-2, which may be useful in both the developed world as well as in low- and middle-income countries",N/A,,-99,University of Washington Foundation,2350418,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24855,INV-017214,to create a continually updating symptom profile of the patients screened and tested for SARS-CoV-2.,N/A,,-99,Stanford University,50000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24856,INV-017384,to support SHEEO members in assessing the short and long term financial impacts of COVID-19,N/A,,-99,State Higher Education Executive Officers Association,138000,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P24857,INV-017453,to screen ReFrame library to identify molecules active on COVID-19,N/A,,-99,The University of Alabama at Birmingham,124921,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24858,INV-006278,to support a series of action studies to summarize social organizations'Äô responses at the forefront of COVID-19 relief efforts and the implications for peer organization and future learning,N/A,,-99,Ginkgo Foundation,150000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,"Secondary impacts of disease, response & control measures",,2020 +P24859,INV-006404,To generate insights on the transmission dynamics of nCoV and COVID-19 in settings of a rapidly evolving outbreak and high population density.,N/A,,-99,KT Corporation,5054353,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | South-East Asia,,,,,South Korea,,Epidemiological studies,Disease transmission dynamics,2020 +P24860,INV-016932,to support the response to COVID-19 in Bangladesh,N/A,,-99,Child Health Research Foundation (CHRF),1496359,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Bangladesh,,,,2020 +P24861,INV-004259,"to work primarily on mAbs for Malaria, a disease which disproportionately impacts the developing world, and COVID-19 mAbs",N/A,,-99,"Curia Bio, Inc.",1310303,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24862,INV-006376,To support serological investigation in Shenzhen to assess resurging risks of COVID-19 or outbreaks and provide guidance on targeted outbreak response measures after the release of containment,N/A,,-99,Shenzhen Center for Disease Control and Prevention,257250,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P24863,INV-016910,to improve our understanding of covid-19 disease,N/A,,-99,University of Washington Foundation,320000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24864,INV-017307,to plan for how to produce more equitable value for students in response to COVID-19 challenges,N/A,,-99,Arizona State University Foundation for A New American University,100000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24865,INV-017145,to quickly provide high-frequency data on the economic impacts of Covid-19 in six key Sub-Saharan African economies to inform urgent public policy decisions,N/A,,-99,FinMark Trust,690000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +P24866,INV-006261,"to provide evidence-based recommendations and technical assistance to improve China public health governance and system to better response to the pandemics such as COVID-19 outbreaks, in China and Globally",N/A,,-99,Tsinghua University,1000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,China,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +P24867,INV-006277,"to support the epidemiology study and identify the high risks of COVID-19 infection, which will contribute to national and international public health intervention strategy and product development",N/A,,-99,Fudan University,300000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,Epidemiological studies,Disease susceptibility,2020 +P24868,INV-017069,"to provide effective, accessible, scalable treatment for covid-19",N/A,,-99,University of Minnesota,3268572,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24869,INV-016365,"to provide representative data on household responses to and impacts from COVID-19 related to health, economic, education, household adaptation, sources of information, etc. for comparison across the outbreak of the disease",N/A,,-99,University of Southern California,733477,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,Data Management and Data Sharing,,,United States of America,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P24870,INV-017062,to rapidly assess the impact of therapeutic drugs to reduce viral shedding and progression of early SARS-CoV-2 infection,N/A,,-99,University of Washington Foundation,5799848,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",,2020 +P24871,INV-016805,to provide emergency relief support in response to the COVID-19 pandemic in Ethiopia,N/A,,-99,American International Health Alliance,2000000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,"Secondary impacts of disease, response & control measures",,2020 +P24872,INV-017329,to plan for creation of equitable value for postsecondary students in response to COVID-19 challenges,N/A,,-99,Southern New Hampshire University,100000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24873,INV-015884,to deploy resources in LMICs with limited or no diagnostic capacity for surveillance (clinical) and diagnosis of SARS-CoV-2.,N/A,,-99,Fondation Merieux,271711,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,France,,Health Systems Research,Health service delivery,2020 +P24874,INV-016637,to create interactive surveys that participants may complete through their mobile devices or on the web to track the spread of COVID-19,N/A,,-99,"The How We Feel Project, Inc.",23000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24875,INV-016908,"to strengthen the response strategies of the Burkina Faso, DRC MoHs to the current outbreak of COVID-19, among other African countries, and to share expertise in epidemic preparedness and response",N/A,,-99,"ALIMA USA, Inc.",200000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24876,INV-017026,to evaluate the efficacy of a single dose of azithromycin in the treatment of outpatient COVID-19 to prevent progression to hospitalization and severe disease.,N/A,,-99,University of California San Francisco,557040,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2020 +P24877,INV-017141,"to strengthen the Government of Mali in its COVID-19 surveillance and response, and collect supporting sero-epidemiological and health system data",N/A,,-99,Tampere University,1000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Finland,,Epidemiological studies | Health Systems Research,Disease transmission dynamics | Health information systems,2020 +P24878,INV-015719,"to strengthen the public health response to Covid-19 in Pakistan, a key regional partner in South Asia, through support for epidemiological and laboratory capabilities.",N/A,,-99,"National Institute of Health Islamabad, Pakistan",2000005,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,Pakistan,,Epidemiological studies,,2020 +P24879,INV-016201,to improve our understanding of Covid-19 disease,N/A,,-99,University of Oxford,310970,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United Kingdom,,,,2020 +P24880,INV-016548,to collect nationally representative data from school leaders and teachers on impact of COVID-19 in the US,N/A,,-99,RAND Corporation,275000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24881,INV-016931,to develop a clinical study protocol and platform to support the evaluation of re-purposed drugs to prevent COVID-19 infection in health care workers,N/A,,-99,Washington University,250000,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +P24882,INV-016076,to respond to the COVID-19 pandemic by developing a SARS-CoV-2 vaccine evaluated through Phase 1 clinical testing,N/A,,-99,Biological E. Limited,4019427,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,India,,"Vaccines research, development and implementation",Phase 1 clinical trial,2020 +P24883,INV-006131,"to establish animal models for COVID-19 infection, to define the pathogenesis and immunology of infection, and to utilize these models to test vaccines and/or therapeutics",N/A,,-99,Beth Israel Deaconess Medical Center Inc.,4352365,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Immunity | Disease models | Disease pathogenesis | Pre-clinical studies | Pre-clinical studies,2020 +P24884,INV-016562,to provide support for coordination of federal and state resources benefitting districts in response to the disruption of education due to the COVID-19 outbreak,N/A,,-99,Council of Chief State School Officers,500314,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P24885,INV-016048,to support the Risk Communication segment of the COVID 19 Response plan of the Ministry of Health & Family Welfare in the states of Bihar and Uttar Pradesh,N/A,,-99,United States Fund for UNICEF,306180,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,"Policies for public health, disease control & community resilience",Communication,2020 +P24886,INV-016715,to accelerate the understanding of medical progression of Covid-19 patients,N/A,,-99,EvergreenHealth,15000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2020 +P24887,INV-016284,to improve our understanding of Covid-19 disease,N/A,,-99,Ajou University Industry-Academic Cooperation Foundation,100000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,South Korea,,,,2020 +P24888,INV-015900,"to support global COVID-19 detection and response by leveraging GISRS platform for sentinel surveillance in low and middle income countries in WHO AFRO, SEARO, and EMRO regions",N/A,,-99,World Health Organization,2980849,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas | South-East Asia,,,,,Switzerland,,,,2020 +P24889,INV-006099,to screen prioritized FDA-approved drugs against SARS-CoV-2 in vitro,N/A,,-99,"University of Maryland, Baltimore",717958,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P24890,INV-006366,to screen Reframe library against Covid-19,N/A,,-99,Katholieke Universiteit Leuven,1145267,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Belgium,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24891,INV-016506,to assist the Government of Afghanistan and partners in the COVID-19 response by protecting frontline workers and vulnerable communities,N/A,,-99,United States Fund for UNICEF,500000,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24892,INV-016204,to evaluate post-exposure prophylactic measures against COVID-19 disease,N/A,,-99,University of Washington Foundation,9519680,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,Clinical characterisation and management | Infection prevention and control,"Supportive care, processes of care and management",2020 +P24893,INV-016377,to support critical gaps to fully implementing COVID-19 surveillance and response in Africa as well as ensure ongoing quality for all technical areas,N/A,,-99,African Field Epidemiology Network,2000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,Uganda,,,,2020 +P24894,INV-016464,to support the Seattle Foundation's COVID-19 Response Fund.,N/A,,-99,Seattle Foundation,1000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24895,INV-016474,to support the COVID-19 Response Fund at the Greater Tacoma Community Foundation,N/A,,-99,Greater Tacoma Community Foundation,250000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24896,INV-016624,to support the Innovia Foundation COVID-19 Community Response Fund,N/A,,-99,Innovia Foundation,250000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24897,INV-006133,to identify potent anti-SARS-CoV-2 mAbs to protect vulnerable populations from COVID-19,N/A,,-99,La Jolla Institute for Immunology,2730874,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24898,INV-016362,"to strengthen preparedness, detection and response to COVID-19, globally",N/A,,-99,CDC Foundation,1100000,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,South-East Asia,,,,,United States of America,,,,2020 +P24899,INV-016357,to support Public Health Seattle-King County COVID-19 response and mitigation efforts,N/A,,-99,King County - Public Health - Seattle & King County,1000000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24902,INV-015823,To support global COVID-19 detection and response in the Gambia,N/A,,-99,London School of Hygiene and Tropical Medicine,74976,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United Kingdom,,,,2020 +P24903,INV-006010,to produce models that will assist Low and Middle Income Countries in planning response activities for 2019-nCoV,N/A,,-99,Northeastern University,357929,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P24904,INV-016202,to assess burden of SARS-CoV-2-infections in African adults in a setting with high HIV and TB prevalence,N/A,,-99,Wits Health Consortium (Pty) Ltd,880490,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,South Africa,,Epidemiological studies,Disease surveillance & mapping,2020 +P24905,INV-016333,to supply urgently needed materials to the UW site for the upcoming hydroxychloroquine(HCQ) post-exposure prophylaxis trial of persons with known COVID-19 exposure,N/A,,-99,University of Washington Foundation,96600,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,,,2020 +P24906,INV-006104,"To support epidemiological prediction and risk assessment, which will facilitate an evidence-based decision-making and allocoation of medical resourses during the battle over COVID-19 outbreak",N/A,,-99,Xi'Äôan Jiaotong University,100000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,Animal and environmental research and research on diseases vectors,,China,,Epidemiological studies,Disease susceptibility,2020 +P24907,INV-006105,to support colloidal gold and ELISA diagnosis of COVID-19 to speed up innovation and increase the availability of effective and large-scale products for the sustainable distribution and use in both China and Foundation'Äôs target countries,N/A,,-99,Sino Biological Inc.,200000,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24908,INV-006106,To support the post-licensure clinical evaluation and comparison studies of nucleic acid detection reagent to demonstrate the key factors impact the sensitivity and specificity of diagnostics reagents of COVID,N/A,,-99,"Shanghai ZJ Bio-Tech Co., Ltd.",100000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P24909,INV-016006,to strengthen the response capacities of Senegal'Äôs Ministry of Health and Social Action and Cameroon'Äôs Ministry of Public Health to COVID-19,N/A,,-99,"ALIMA USA, Inc.",500000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa,,,,,United States of America,,,,2020 +P24910,INV-006113,to support the modeling of COVID-19,N/A,,-99,University of Washington Foundation,100000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,United States of America,,,,2020 +P24911,INV-005834,"to support innovation of vaccine and Point of Care Testing (POCT) through epitope identification, the modeling outputs of which will facilitate an evidence-based decision-making during the battle over 2019-nCoV outbreak",N/A,,-99,Xiamen University,600000,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,,,2020 +P24912,INV-006200,to allow WHO to build surge capacity to detect and respond to COVID-19.,N/A,,-99,World Health Organization,7000000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,Switzerland,,,,2020 +P24913,INV-005999,to strengthen epidemic preparedness capacity and mitigate harm related to the 2019 novel coronavirus (nCoV) in the African region,N/A,,-99,"Vital Strategies, Inc.",999450,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Africa | Americas,,,,,United States of America,,,,2020 +P24914,INV-005840,"To support the study of clinical epidemiology for 2019-nCoV outbreak and evaluation of IVD Diagnostics in China, which will contribute national and international public health intervention strategy development to against 2019-nCoV",N/A,,-99,The Third People'Äòs Hospital of Shenzhen,500000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Unspecified,,,,,China,,Epidemiological studies,Disease transmission dynamics,2020 +P24915,INV-017570,to capture Florida district responses to the COVID-19 crisis.,N/A,,-99,University of Florida,106760,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bill & Melinda Gates Foundation,United States of America,Americas,Americas,,,,,United States of America,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P24916,SE0572,SE0572: Developing capability for detection of Monkeypox exposure in animals - SE0572,"Monkeypox (MPX) is a zoonotic viral disease clinically similar to smallpox, although less severe. The disease is caused by monkeypox virus (MPXV) which is predominantly found in west and central Africa. Monkeypox virus is an enveloped double-stranded DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family, that is occasionally transmitted to humans from animal host (reservoir) species, including rope squirrels, tree squirrels, Gambian pouched rats, dormice, non-human primates and other species.There are two distinct genetic clades of the MPXV: the central African (Congo Basin) clade and the west African clade. The current MPX outbreak is caused by the west African clade, which historically causes a less severe form of disease than the Congo Basin clade with disease symptoms/clinical signs usually lasting between 2 to 4 weeks with case fatality ratio around 1'Äì3%. Monkeypox is a disease of global public health importance as it not only affects countries in west and central Africa, but the rest of the world. In 2003, the first monkeypox outbreak outside of Africa was in the United States of America and was linked to contact with infected pet prairie dogs. These pets had been housed with Gambian pouched rats and dormice that had been imported into the country from Ghana. This outbreak led to over 70 cases of monkeypox in the U.S.A. Monkeypox has also been reported in travelers from Nigeria to Israel in September 2018, to the United Kingdom in September 2018, December 2019 and May 2021. In 2022, MPX has been reported in 13 non-endemic countries, including Australia, North America, Europe and United Kingdom (over 100 cases) to date. The spread of MPXV between different semi-wild animal species and subsequent transmission to humans was documented in North America in 2003, where imported animals infected with MPX were housed with semi-wild animals which later developed signs of MPXV infection after being sold. Consequently, 47 confirmed and probable animal to human cases (no human to human transmission cases) were reported (HAIRS 14). Human to human transmission may occur through contact with clothing or linens (such as bedding or towels) used by an infected person, direct contact with MPX skin lesions or scabs, or through respiratory droplets when an infected person with a MPX rash coughs or sneezes (HAIRS 13). Although animal to human and human to human transmission of MPXV is known and has been documented a number of times, human to animal transmission is poorly understood. During MPX outbreaks there is a low but potential risk of transmission to companion/pet animals from MPXV infected humans when housed together in close proximity. Infected pets pose a threat to the continual spread of virus and disease especially when the animals are subclinical and/or are not diagnosed. If companion animals were to be infected there is a possibility that virus may be transmitted to susceptible wildlife species, with rodents being the most likely scenario. This project will be used to develop APHA's and the UK's preparedness to test suspect animals, including companion/pet animals, to confirm the presence of virus in cases of known or probable exposure and/or absence of infection post isolation/quarantine restriction periods. The project will also be used to develop tools to study MPXV pathogenicity in companion and wild animals, building validated capability and capacity.",,2023,APHA (Animal and Plant Health Agency),119388.6,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,Europe,Europe,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Development of equitable, accessible, safe & effective diagnostics (including POC) | Investigation of zoonotic transmission & reservoirs",United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Animal source and routes of transmission,2022 +P24918,SE0562,"EJPOH SE0562: SARS-CoV-2 Research Integration and preparedness (COVID19JIP) COVRIN. One Health research integration on SARS-CoV-2 emergence, risk assessment and preparedness - SE0562","Coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in December 2019 in Wuhan, China, and has since spread rapidly, evolving into a full-blown pandemic. This COVID-19 pandemic has had an unprecedented societal and economic impact. Therefore, the OHEJP Project Management Team (PMT) on behalf of its partners has decided that they should join forces to combat COVID-19 and raise preparedness for future coronavirus outbreaks. A main focus of this OHEJP initiative will be to reinforce collaboration and integration of research activities by means of a Joint Integrative Project (JIP) on SARS-CoV-2. This JIP aims to integrate coronavirus research activities of all OHEJP partners. The project will have two main operational objectives: The first will be to identify the drivers for the emergence and spread of SARS-CoV-2. The second will be to generate data and build models for risk assessment of SARS-CoV-2. Besides a work package on coordination and communication, including activities to connect with stakeholders and avoid overlaps with other projects, the project will have four integrative research work packages. The integrative research activities will include i) research on detection of SARS-CoV-2 in animal species and the environment, ii) research on SARS-CoV-2 molecular and biological characterization, iii) SARS-CoV-2 surveillance and risk assessment, focussed on the animal-human interface, and iv) coronavirus preparedness. Through this work COVRIN will achieve the following strategic goals. 1) Develop common COVID-19 protocols that support OHEJP collaborations, 2) develop a common infrastructure for COVID-19 research, 3) integrate COVRIN deliverables into the work processes of OHEJP partners, 4) reduce overlaps of COVID-19 research within OHEJP, and 5) develop a common OHEJP structure on coronavirus preparedness. The Coronavirus research integration (COVRIN) project is being led Wageningen Bioveterinary Research in the Netherlands and the University of Surrey, along with contributions from 19 other partners already involved within the OHEJP. Within the overall EJP One Health strategic goals, the overall aim of COVRIN will be to generate and share data of integrative research activities on virus-host interactions, virus evolution and drivers for emergence, risk assessment and risk modelling, in order to increase the preparedness for future Coronavirus outbreaks.",,2023,APHA (Animal and Plant Health Agency),128268.4,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,Europe,Europe,Data Management and Data Sharing,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics",2021 +P24919,SE0563,UKRI: SARS-Cov-2 infection at the animal-human interface: longevity and re-infection dynamics with virus evolution. - SE0563,Aims: A. To assess virological parameters in longitudinal infection including delineating between 'Äòinfected'Äô (virus genome) and 'Äòinfectious'Äô (viable/transmissible virus) during the course of infection. B. Investigate the longevity of SARS-CoV-2 immunity in SARS-CoV-2 infection and re-infection with human and 'Äòanimal-like'Äô SARS-CoV-2 virus variants. C. To assess the potential for re-infection with SARS-CoV-2 and assess the parameters around virus kinetics human and 'Äòanimal-like'Äô SARS-CoV-2 virus variants. D. Investigate how genetically different virus variants alter the potential or parameters in re-infection. E. Investigate the role of re-infection in onward transmission with human and 'Äòanimal-like'Äô SARS-CoV-2 virus variants. F. To characterise the effect of natural immunity on virus evolution with human and 'Äòanimal-like'Äô SARS-CoV-2 virus variants.,,2023,APHA (Animal and Plant Health Agency),803810.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Department for Environment, Food and Rural Affairs (DEFRA)",United Kingdom,Europe,Europe,Europe,,,,United Kingdom,United Kingdom,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P24920,N/A,Akagera - Disease X,"CEPI to provide up to US $1.46 million to Akagera Medicines to advance innovative lipid nanoparticles and modified mRNA for the development of a multivalent influenza vaccine. Technology could reduce reactogenicity of and improve access to mRNA vaccines, with potential applications to other future emerging infectious disease outbreaks. Dec 19, 2023; OSLO, NORWAY; KIGALI, RWANDA, BOSTON, USA: At a press conference in Kigali, Rwanda, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Rwandan-US Akagera Medicines today announced a partnership which aims to improve existing mRNA technology by reducing reactogenicity and improving equitable access to mRNA vaccine doses, for example by removing the need for frozen storage. CEPI will initially provide up to USD 1.46 million to demonstrate the pre-clinical proof of concept of Akagera Medicine's innovative lipid nanoparticles (LNPs) and modified mRNA for the development of a multivalent influenza vaccine. The outcomes of this partnership could better prepare the world for future epidemic and pandemic threats, including an as-of-yet unidentified pathogen known as Disease X, in alignment with the 100 Days Mission. The 100 Days Mission is an ambitious goal spearheaded by CEPI, and embraced by leaders of the G7 and G20, that aims to accelerate vaccine development to around 100 days from virus identification, potentially stopping a future outbreak in its tracks. Improving mRNA technology to end future outbreaks and pandemics faster Advances in mRNA vaccine technology have been critical to the global response to COVID-19, saving millions of lives. Still, the reactogenicity of mRNA vaccines'Äîthat is, the side effects or reactions post-vaccination'Äîis a challenge. Although such reactions are generally mild and short-lived and an indicator that the body is responding to a vaccine and building protection, these reactions may contribute to vaccine hesitancy. Like many other mRNA vaccines, Akagera Medicine's technology uses LNPs to encase and protect fragile mRNA molecules, but their innovative LNP formulation could optimise delivery of mRNA and reduce potential LNP-associated adverse events. The technology could also improve the stability of the mRNA-based vaccines, removing the need for frozen storage. This is particularly crucial in addressing access to mRNA vaccines in remote or low-resource settings, which may lack the infrastructure and technologies needed to support ultra-low cold-chain. Akagera Medicine's technology could offer additional potential benefits that would further bolster equitable vaccine access, including enhanced shelf life, reduced Cost of Goods, and a reduction in the required effective dose, which would extend the number of doses that could be produced. Dr. Richard Hatchett, CEO of CEPI, said: ""As we reflect on the critical role of mRNA vaccines in the battle against the COVID-19 pandemic, it's evident that improvements are needed to make the technology more accessible, particularly for people living in low-resource settings. Our partnership with Rwandan-owned Akagera Medicines aims to release mRNA vaccines from the limits of frozen storage and minimize their side-effects, thereby creating an even more impactful and accessible defence against emerging infectious disease threats. Rwanda is a regional leader in health innovation and has made great progress in effectively translating such innovation to address public health challenges. I look forward to strengthening our partnerships with Rwanda's burgeoning life-sciences sector."" Dr. Daryl Drummond, PhD, Chief Science Officer at Akagera Medicines, said, ""We founded Akagera Medicines to create medicines that lead to a world free of tuberculosis (TB), humankind's greatest killer. This means improving efficacy, shortening the duration of treatment, optimizing drug/drug interaction, eliminating toxicity, and lowering the costs to patients and to society. We also intend to complete the development of our vaccine delivery system in 2025 that can be used for TB, Lassa fever, HIV, COVID, influenza and other infections. This delivery system, our patent-protected mRNA lipid nanoparticle, avoids intra-muscular reactions, passes through the lymph system, and targets and binds to the dendritic cells at the gateway of the immune system."" Michael Fairbanks, Executive Chairman at Akagera Medicines, said ""We are honoured to partner with CEPI, one of the global organizations most critical to fighting pandemics. CEPI helps companies to learn and overcome challenges in return for sharing that learning with other firms and multilateral organizations who are also dedicated to global healthcare equity."" Regis Rugemanshuro, CEO of the Rwanda Social Security Board, the majority owners of Akagera Medicines, also added, ""Akagera Medicines is the only African-owned company that has potential solutions to tuberculosis, Lassa fever and HIV. We welcome the partnership with CEPI, one of the world's best hopes to fight the next pandemic, because it will help Africa achieve our goals."" This funding forms part of CEPI's programme to advance novel RNA vaccine platform technologies for emerging and select endemic infectious diseases, which could offer substantial advantages over existing mRNA technologies, such as multivalency, improved immunogenicity, storage and stability, productivity, response time, and cost-of-goods. Novel mRNA technologies, such as the one being developed by Akagera, could make a vital contribution to the proposed Global Vaccine Library. Central to the 100 Days Mission, a Global Vaccine Library is envisaged as a global repository of vaccine resources, capabilities, and data which could be pulled 'Äòoff the shelf' and quickly adapted in response to a future outbreak, accelerating the development of life-saving vaccines. Enabling equitable access to vaccines CEPI and Akagera Medicines are committed to enabling equitable access to the outputs of this CEPI-supported programme, in line with CEPI's Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results including data generated as part of this project will be published open access for the benefit of the global scientific community. 'ÄîENDS'Äî About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of over 30 vaccine candidates against its priority pathogens'ÄîChikungunya virus, Ebola Virus Disease, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and SARS-CoV-2'Äîand is a leading funder of research into broadly protective coronavirus vaccines, which could protect against future variants of COVID-19 as well as other coronaviruses with epidemic and pandemic potential. The organization has also invested in the development of rapid response platforms to develop vaccines against Disease X (the threat of an unknown virus). CEPI has overseen a number of scientific breakthroughs, including the first Phase 3 trial of a Chikungunya vaccine and the advancement of the first ever Nipah and Lassa vaccines into Phase 1 trials. The organization played a central role in the global response to COVID-19, supporting the development of one of the world's largest portfolios of vaccines against SARS-CoV-2, seven of which have been approved for domestic or global use. It also co-led COVAX, the global initiative to deliver fair and equitable access to COVID-19 vaccines, which has delivered approximately 2 billion doses of vaccine to 146 countries around the world. CEPI's five-year plan for 2022-2026 aims to dramatically reduce or even eliminate the future risk of pandemics and epidemics. Central to the plan is CEPI's goal to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. Achieving this 'Äò100 Days Mission', which has been embraced by the G7 and G20, would give the world a fighting chance of containing a future outbreak before it can spread to become a global pandemic. Visit our news page for the latest updates. Follow us via @CEPIvaccines, @DrRHatchett, LinkedIn, and Facebook. About Akagera Medicines Akagera Medicines develops novel liposomal formulations of antibacterial therapeutics and vaccines to treat tuberculosis, Lassa Fever, HIV, influenza and other infectious diseases. The company was founded in 2018 in Kigali, Rwanda. It is majority-owned by the people of Rwanda through the Rwanda Social Security Board (RSSB), registered as a Delaware corporation, and has laboratories in Boston and San Francisco. Its partners include CEPI, the Gates Foundation, the National Institute of Health (VRC), the European Commission and the European Investment Bank. Akagera Medicines registered a subsidiary in Kigali in 2021 to do manufacturing and clinical trials in the future. Founding board members and advisors include Ambassador Dr. Albrecht Conze, Dr. Paul Farmer, Dr. Donald Kaberuka, and Dr. Anne Lenaerts. Please visit our webpage at Akageramedicines.com. Media contacts CEPI E: press@cepi.net P: +44 7387 055214 Akagera Medicines Michael Fairbanks, Executive Chairman and Cofounder Mfairbanks@akageramed.com",,-99,Akagera Medicines,1500000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Lassa fever | COVID-19 | Pandemic-prone influenza | Disease X,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Africa,,,,,Rwanda,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2023 +P24921,N/A,Auro Vaccines - Nipah,"Pearl River, NY, USA, Seattle, WA and Oslo, Norway, March 13, 2020 'Äî A Phase 1 clinical study of a Nipah virus vaccine candidate (HeV-sG-V) is underway. This trial marks the first time a vaccine developed to prevent Nipah virus infection will be studied in humans. No vaccines currently exist to protect against the deadly virus and the only treatment available is supportive care. CEPI first announced up to $25 million of funding for this programme in May, 2018. The Phase 1 trial is a randomised, placebo-controlled, dose-finding study to investigate the safety, tolerability and immunogenicity of HeV-sG-V Nipah vaccine candidate. The study, sponsored by Auro Vaccines LLC and led by PATH, is being conducted at the Cincinnati Children's Hospital Medical Center in Cincinnati, USA. More information about the trial can be found using the ClinicalTrials.gov Identifier, NCT04199169. The HeV-sG-V Nipah vaccine candidate The Nipah virus vaccine programme is the result of a global partnership between Auro Vaccines, PATH and CEPI. The vaccine was originally developed by Dr. Christopher Broder and Dr. Katharine Bossart at the US government's Uniformed Services University of the Health Sciences (USU, Bethesda, MD). The HeV-sG-V Nipah vaccine candidate is a recombinant subunit vaccine that contains a portion of the G glycoprotein of Hendra virus, a henipavirus closely related to Nipah. HeV-sG-V has been shown in preclinical studies to protect against Nipah virus and Hendra virus and has been licensed to Auro Vaccines from The Henry M. Jackson Foundation for the Advancement of Military Medicine, (HJF) through the USU/HJF Joint Office of Technology Transfer, to develop the human vaccine. Auro Vaccines, with the support of CEPI, will be sponsoring the Phase 1 study; PATH, an international global health organisation, is leading clinical operations; and CEPI is funding the programme through Phase 2 clinical study. Under the terms of the Framework Partnering Agreement originally awarded by CEPI for the collaboration among the three parties, Emergent BioSolutions Inc. has provided contract development and manufacturing services out of its Gaithersburg and Baltimore facilities in Maryland to produce the Phase 1 clinical trial material. Emergent, through a separate agreement with Auro Vaccines, has an exclusive option to license and to assume control of development activities for the Nipah virus vaccine candidate.",,-99,Auro vaccines & PATH,25000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,South-East Asia,,,,,India,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2020 +P24924,N/A,BioNTech - mpox,"BioNTech is initiating a phase 1/2 clinical trial of the mRNA-based mpox vaccine program, BNT166 The Coalition for Epidemic Preparedness Innovations (CEPI) commits funding of up to $90 million for the development of vaccine candidates Data generated by this partnership will contribute to CEPI's 100 Days Mission, a global effort to accelerate the development of well-tolerated and effective vaccines against future viral threats with pandemic potential The partnership is part of BioNTech's strategy to develop novel prophylactic vaccines for the prevention of high-medical-need infectious diseases, including diseases that disproportionally affect lower-income countries MAINZ, Germany, and OSLO, Norway, September 18, 2023 'Äî BioNTech SE (Nasdaq: BNTX, ""BioNTech"", ""the Company"") and the Coalition for Epidemic Preparedness Innovations (CEPI) today announced a strategic partnership to advance mRNA-based vaccine candidates with the development of BNT166 for the prevention of mpox (formerly monkeypox, caused by a member of the Orthopoxvirus viral family), an infectious disease that can lead to severe, life-threatening complications. Mpox gained global attention in May 2022 with an increasing number of cases that then developed into an international outbreak. CEPI will provide funding of up to $90 million to support the development of mRNA-based vaccine candidates. The mpox vaccine program BNT166 is part of BioNTech's efforts to develop novel prophylactic vaccines for a range of infectious diseases with a high medical need, including indications that are disproportionally prevalent in lower-income countries. Since the eradication of smallpox in 1980, the global population-level immunity against the Orthopoxvirus viral family, including mpox, has been waning. BioNTech is aiming to develop a prophylactic mRNA-based mpox vaccine with a favorable safety profile that can be manufactured at scale. The strategic partnership between BioNTech and CEPI is aiming to contribute to CEPI's 100 Days Mission, a global goal to accelerate development of well-tolerated and effective vaccines against a potential future pandemic virus so that a vaccine can be ready for regulatory authorization and manufacturing at scale within 100 days of recognition of a pandemic pathogen. This mission is spearheaded by CEPI and embraced by the G7, G20, and industry leaders. The partnership between BioNTech and CEPI could help accelerate responses to future outbreaks caused by viruses of the Orthopoxvirus viral family in several ways. For example, advancing the development of an mRNA-based mpox vaccine candidate, if successfully approved and authorized, could help provide larger supplies of vaccines for use against future mpox outbreaks. In addition, the data generated could contribute to the rapid development of mRNA-based vaccines against future outbreaks caused by Orthopoxviruses. ""Mpox can cause severe complications, particularly in children and pregnant women as well as in immunocompromised individuals. The global outbreak, which was declared a public health emergency of international concern, underlines the need for a highly effective, well-tolerated, and accessible mpox vaccine. We initiated our BNT166 program in May 2022 to help address this need,"" said Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech. ""We believe our scientific approach as well as our mRNA technology have the potential to significantly contribute to deliver on CEPI's 100 Days Mission."" ""The 100 Days Mission aims to accelerate the development of a vaccine against a novel virus with pandemic potential to just 100 days, and BioNTech's world-class scientists, technology and facilities can make a vital contribution. Achieving this mission, and potentially preventing the next pandemic, will require gathering a wealth of knowledge and data about the performance of the latest vaccine platforms, like mRNA, which can enable rapid responses to emerging infectious threats across a broad range of viruses. Our work on mpox could broaden the portfolio of vaccines available against this potentially deadly disease, while building our understanding of how mRNA technology performs against Orthopoxviruses, a family of viruses that have long afflicted humankind and remain an ongoing threat today,"" said Richard Hatchett, M.D., Chief Executive Officer of CEPI. The BNT166 vaccine candidates encode surface antigens that are expressed in the two infectious forms of the monkeypox virus (MPXV) to efficiently fight virus replication and infectivity. The clinical trial (NCT05988203) will evaluate the safety, tolerability, reactogenicity and immunogenicity of two mRNA-based multivalent vaccine candidates for active immunization against mpox. The phase 1/2 trial aims to enroll 196 healthy participants with and without prior history of known or suspected smallpox vaccination (vaccinia-naive participants). BNT166 is part of BioNTech's infectious disease programs aiming to provide equitable access to effective and well-tolerated vaccines for high medical need indications. This includes BioNTech's Malaria and Tuberculosis programs, BNT165 and BNT164, respectively, which are both currently in Phase 1 clinical trials. BioNTech's efforts also include the establishment of a decentralized and robust end-to-end manufacturing network in Africa aiming to enable scalable production of mRNA-based medicines. The first manufacturing site based on the Company's state-of-the-art, scalable BioNTainer solution is currently being built in Kigali, Rwanda. BioNTech and CEPI are committed to enabling equitable access to the outputs of this partnership. Any licensed vaccines developed as a result of this strategic partnership are expected to be made available at affordable prices in low- and middle-income countries.",,-99,BioNtech,90000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Poxviridae,,,,,,,,,Mpox,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Europe,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",Germany,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2023 +P24928,N/A,Chungbuk National University - Disease X,"Novel self-amplifying design has the potential to reduce dosage and cost of vaccines, supporting rapid global rollout in response to an emerging infectious disease outbreak. 12 December 2023, OSLO, Norway and SEOUL, South Korea 'Äî The Coalition for Epidemic Preparedness Innovations, CEPI, has partnered with Korea's Chungbuk National University (CBNU) to advance development of CBNU's self-amplifying mRNA vaccine technology. The partnership aims to better prepare the world for future epidemic and pandemic threats, including an unknown or as-of-yet unidentified pathogen, known as Disease X, in pursuit of the 100 Days Mission. Advances in mRNA vaccines have been critical to the global response to COVID-19 and the technology has been identified as a pivotal enabler of rapid outbreak management. As part of its plan to expand use of and access to novel mRNA innovations which can further bolster global pandemic preparedness, CEPI will provide CBNU with up to US $1 million in seed funding to support evaluation of the immune response and efficacy of their mRNA vaccine technology in preclinical models. With CEPI's support, CBNU will first assess the platform against avian influenza H5N1 virus. The findings will provide a model to help assess this new technology and explore how it could be used to rapidly respond to a future Disease X in as little as 100 days. The 100 Days Mission is an ambitious goal spearheaded by CEPI, and embraced by the Republic of Korea as part of its strategic plan against emerging infectious diseases, that aims to accelerate vaccine development to around 100 days from virus identification, potentially stopping a future outbreak in its tracks before it becomes a pandemic. In addition to accelerating future outbreak response, CBNU's innovative technology could also enhance accessibility to mRNA vaccines. The self-amplifying design works by giving the body instructions to replicate mRNA which could amplify the amount of protein made and reduce the amount of antigen, necessitating fewer vaccine doses and reducing the cost of the vaccine. Costs could be further reduced due to the distinctive CBNU vaccine design which proposes replacing the 5'cap 'Äî a typical feature in mRNA 'Äî with an alternative modification. Dr Richard Hatchett, CEO of CEPI, said: ""While mRNA technology transformed our response to the COVID-19 pandemic, we must now invest in promising novel innovations that capitalise on mRNA's transformative qualities to provide more effective responses to future epidemics and pandemics. This new partnership further fortifies our collaborations with Korea's world-leading vaccine sector, with Chungbuk National University's mRNA technology offering advantages against existing mRNA platforms which could improve access to such vaccines in the future."" ChangSeop Koh, President of Chungbuk National University, said: ""We are extremely proud and excited to collaborate with CEPI on this groundbreaking project. This partnership highlights the innovative capacity of Chungbuk National University's research and places us at the forefront of global efforts to respond to future pandemics. Our self-amplifying mRNA technology provides higher efficiency without the need for costly manufacturing materials used in conventional mRNA vaccines. This technology promises to bring significant changes in vaccine development, offering faster, cost-effective, and adaptable solutions to new health threats. Our collaboration with CEPI demonstrates our commitment to advancing global public health and ensuring equitable access to life-saving vaccines. We are dedicated to using our expertise and resources to make a significant impact in the global fight against infectious diseases."" CEPI's investment in CBNU's novel mRNA innovation is the latest partnership to be established as part of its programme to advance novel RNA vaccine platform technologies for emerging and select endemic infectious diseases. The programme seeks to evaluate whether the next-generation of RNA technologies, such as self-amplifying platforms, could offer substantial advantages over existing platforms, for example improved immunogenicity, storage, stability, productivity, response time, and cost-of-goods. Novel mRNA technologies such as the one being developed by CBNU could make a vital contribution to the proposed Global Vaccine Library. Central to the 100 Days Mission, a Global Vaccine Library is envisaged as a global repository of vaccine resources, capabilities, and data which could be pulled 'Äòoff the shelf' and quickly adapted in response to a future outbreak, accelerating the development of life-saving vaccines. CEPI and CBNU are committed to enabling equitable access to the outputs of this CEPI-supported programme, in line with CEPI's Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results including data generated as part of this project will be published open access for the benefit of the global scientific community. Korea: A driving force in global vaccine development The new partnership with CBNU extends CEPI's breadth of work with academic, government and pharmaceutical sector institutions in Korea, with CEPI having committed up to USD 292 million to partnerships in Korea to date. The Republic of Korea and CEPI representatives recently attended a signing ceremony to formalise Korea's increased USD 24 million investment in CEPI for 2023. CEPI also co-hosted a plenary session with IVI and the Korean Ministry of Health and Welfare last month at the World Bio Summit held in the Republic of Korea titled 'ÄòStrengthening Global Preparedness through CEPI's 100-Days Mission'. ENDS Notes to Editors mRNA vaccine technology mRNA vaccines use the body's own machinery to make antigenic protein rather than injecting the pure antigen directly into the body (an antigen is a foreign substance that induces an immune response). mRNA technology has been identified as a pivotal enabler of the 100 Days Mission due to its flexibility as a rapid-response platform on which new vaccine candidates can be designed and quickly made ready for clinical testing and subsequent scale-up, potentially within days from the moment a new viral threat is identified. Self-amplifying RNA vaccines, like the technology being produced by CBNU, work by incorporating genetic information from a particular group of viruses together with the antigen of interest. The genetic information from the virus programmes the host cell to generate multiple copies of the self-amplifying RNA. The amplification of increases the number of genetic copies of the antigen and, consequently, increases the generation of the antigen protein within the host cell. This has the potential to result in more robust, enduring immunity at lower antigen doses, necessitating fewer vaccine doses and enhancing overall productivity. mRNA-based vaccines typically rely on a 5¬¥cap, a crucial chemical entity for the translation process. However, the associated cap contributes significantly to the high cost of goods. CBNU's distinctive self-amplifying vaccine design proposes replacing the cap with an alternative modification in the RNA sequence. Preliminary results indicate that eliminating the cap not only enhances current RNA technology but also substantially reduces the cost of goods, thereby improving accessibility. CEPI's work in Korea CEPI also hosted an R&D workshop with a broad set of Korean technical stakeholders at the World Bio Summit. In addition, CEPI's Chair had high-level meetings with the Korean Government and the National Assembly. About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of over 30 vaccine candidates against its priority pathogens'ÄîChikungunya virus, Ebola Virus Disease, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and SARS-CoV-2'Äîand is a leading funder of research into broadly protective coronavirus vaccines, which could protect against future variants of COVID-19 as well as other coronaviruses with epidemic and pandemic potential. The organization has also invested in the development of rapid response platforms to develop vaccines against Disease X (the threat of an unknown virus). CEPI has contributed to a number of scientific breakthroughs, including the first ever licensed Chikungunya vaccine and the advancement of the first ever Nipah and Lassa vaccines into Phase 1 trials. The organization played a central role in the global response to COVID-19, supporting the development of one of the world's largest portfolios of vaccines against SARS-CoV-2, seven of which have been approved for domestic or global use. It also co-led COVAX, the global initiative to deliver fair and equitable access to COVID-19 vaccines, which has delivered approximately 2 billion doses of vaccine to 146 countries around the world. CEPI's five-year plan for 2022-2026 aims to dramatically reduce or even eliminate the future risk of pandemics and epidemics. Central to the plan is CEPI's goal to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. Achieving this 'Äò100 Days Mission', which has been embraced by the G7 and G20, would give the world a fighting chance of containing a future outbreak before it can spread to become a global pandemic. Visit our news page for the latest updates. Follow us via @CEPIvaccines, @DrRHatchett, LinkedIn, and Facebook. About Chungbuk National University Chungbuk National University (CBNU), located in Cheongju, South Korea, is a prestigious institution known for its rigorous academic programs and innovative research. Established in 1951, the university has grown into a comprehensive center of higher education, offering a wide range of undergraduate and graduate programs across various disciplines. CBNU is particularly renowned for its cutting-edge research and development in the field of biotechnology and health sciences. The university's commitment to research excellence is evident in its state-of-the-art facilities and laboratories, which foster an environment conducive to groundbreaking discoveries and advancements. The university's collaborative approach to research, engaging with both national and international partners, has positioned CBNU as a leader in addressing global health challenges. Its recent partnership with CEPI underscores CBNU's dedication to developing novel medical solutions, particularly in the realm of vaccine development, to combat emerging infectious diseases. At CBNU, education and research go hand in hand, with a focus on nurturing the next generation of scientists, healthcare professionals, and innovators. The university's faculty comprises distinguished scholars and researchers who are dedicated to providing high-quality education and mentorship, preparing students to make meaningful contributions in their respective fields. CBNU's vision extends beyond academic excellence, aiming to make a significant impact on global health and well-being. This commitment is reflected in its ongoing efforts to develop and innovate in areas critical to public health, including the advancement of its novel self-amplifying RNA vaccine technology. For more information, visit CBNU Website. Media Contacts CEPI press@cepi.net +44 7387 055214",,-99,Chungbuk National University,900000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Novel Pathogen,H5,,,,H5N1,,,,Pandemic-prone influenza | Disease X,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Western Pacific,,,,,South Korea,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2023 +P24930,N/A,UC Davis - Rift Valley fever,"CEPI to invest $28.5 million, with support from the EU, in UC Davis-led clinical trials of a Rift Valley fever (RVF) vaccine in Tanzania, a country at high-risk of outbreaks of the disease. Potentially deadly mosquito-borne virus causes great damage to lives and livelihoods, primarily in rural communities in low- and middle-income countries across Africa and beyond. As climate change expands the range of potential RVF outbreaks, trials will meet urgent need for vaccine development progress. 14 September 2023, OSLO Norway and DAVIS, California: Human trials of a novel vaccine against the potentially deadly Rift Valley fever virus (RVF) are to take place in Tanzania 'Äî a country where the mosquito-borne disease poses a significant threat to the lives and livelihoods of people in rural communities. The Coalition for Epidemic Preparedness Innovations (CEPI) will provide funding of up to US$28.5 million, with support from the European Union's Horizon Europe programme, to fund a research team led by the One Health Institute in the School of Veterinary Medicine at University of California, Davis (UC Davis) to conduct Phase I and Phase II trials of a novel RVF vaccine candidate. The studies will be amongst the first CEPI-funded trials to be conducted in a region where RVF is endemic, and will assess the safety and immunogenicity of UC Davis' live-attenuated RVF vaccine, known as DDVax, in people most at risk of RVF infection. The Phase I trial is planned to begin in 2024, subject to regulatory and ethical approvals. DDvax is currently being evaluated in preclinical studies funded by CEPI and the EU under a previous agreement with Colorado State University, UC Davis and partners. In addition to clinical trials in Tanzania, CEPI will fund technology transfer of assays and samples to laboratories in Tanzania, and regulatory engagement to plan a pathway to licensure for the vaccine. The consortium will also carry out comprehensive One Health-oriented epidemiological studies designed to generate valuable scientific knowledge about the sources and drivers of RVF outbreaks, thereby contributing to outbreak prediction and management and guiding late-stage vaccine development planning. Rift Valley fever: a climate-driven disease with epidemic potential RVF is a potentially deadly virus which can spread to people either through mosquito bites or through contact with infected livestock. The disease can cause severe symptoms such as encephalitis and hemorrhaging, and kills around 1 percent of all those it infects. RVF is also profoundly destructive for the livelihoods of those in rural areas where outbreaks occur and often results in large-scale losses of livestock. Because of its impact on both people and animals, RVF is a prime candidate for a 'ÄòOne Health' approach to disease control. No safe and effective human vaccines or treatments have yet been approved for use against RVF, so their development is considered a top priority by both the Africa CDC and the World Health Organization's R&D Blueprint team. RVF was first identified in Kenya's Rift Valley, but in recent decades has steadily extended its reach across much of Africa and parts of the Middle East, putting more people in more countries at risk of infection. Outbreaks of RVF have been consistently linked with intense periods of rainfall and flooding - including those caused by the El Ni√±o phenomenon which has recently returned after a seven year absence. Heavy rains provide ideal conditions for RVF-infected mosquitoes to breed and hatch. As climate change persists, expanding the range of mosquitoes and increasing the likelihood of extreme weather events such as flooding, there is a risk that RVF outbreaks will become more frequent and widespread making the development of a protective human vaccine all the more urgent. Dr Richard Hatchett, CEO of CEPI, said: ""Despite the devastating impact that Rift Valley fever can inflict on the lives and livelihoods of vulnerable communities, no licensed vaccines are available to prevent the disease. Climate change is making weather patterns ever more volatile, increasing the risk of more frequent and widespread outbreaks of this potentially deadly virus, and making the development of safe and effective vaccines more urgent than ever before. Through this partnership, CEPI and EU funding will support UC Davis and its partners to advance this promising vaccine candidate into clinical trials in an endemic country, generating crucial data in the population most likely to benefit from its protection in the future."" Marc Lema√Ætre, Director-General for Research and Innovation, European Commission, said: ""With the memories of the recent pandemic still fresh in our minds, we know how important it is to invest in research to prevent and control the threat from infectious diseases. An effective vaccine against Rift Valley Fever would go a long way to prevent more frequent and deadly outbreaks, with all the serious public health and socioeconomic consequences that we see today. I am pleased to see that this essential research project can now take off with the steadfast support of the European Union and Horizon Europe, through our great collaboration with CEPI. The EU and its Member States have been among the largest contributors to CEPI since its inception. From the EU Framework Programmes for Research and Innovation, we have provided more than EUR 240 million since 2017 and we are proud of the great scientific progress the strong partnership with CEPI has produced on Ebola, Chikungunya, Rift Valley fever, and COVID-19 so far. I am confident that the project starting today will bring us even closer to an effective vaccine against Rift Valley Fever."" Dr Brian Bird, Project Director, UC Davis One Health Institute, said: ""A One Health approach to vaccination and community-based risk reduction activities is essential to control Rift Valley fever. We are tremendously excited to work with CEPI and our partners to evaluate the safety and immunogenicity of DDVax in clinical trials in Tanzania, and to understand the underlying epidemiology of this deadly zoonotic disease. Working together as a multi-disciplinary team we can improve the lives of people, animals, and communities across the world."" Dr Ally Olotu, Head, Department of Interventions & Clinical Trials, Ifakara Health Institute, said: ""Rift Valley fever virus has periodically caused severe outbreaks in Tanzania and across Africa, impacting people's health, their livestock, and socio-economic outcomes. An effective vaccine for humans would be a game changer for public health. The Ifakara Health Institute is delighted to partner with UC Davis and CEPI to evaluate the DDVax candidate, and work to understand the dynamics of RVF transmission to inform vaccine deployment in the future."" This funding is being awarded under a CEPI Call for Proposals designed to support RVF vaccine candidates through clinical trials in endemic areas, which is supported by EUR35m provided by the European Union's Horizon Europe programme. Enabling equitable access to RVF vaccines RVF primarily impacts rural and pastoral communities living in low- and middle-income countries in East Africa. CEPI and the UC Davis-led consortium are committed to enabling equitable access to RVF vaccines to the populations who need them, in line with CEPI's Equitable Access Policy. This includes planning for the potential development of investigational stockpiles for use in outbreak situations, agreeing to an affordable pricing mechanism such as Cost of Goods +%, and endeavouring to manufacture the vaccines at geographically dispersed manufacturing sites close to where outbreaks may occur in order to minimise supply risks. In addition, the clinical trial and epidemiological data generated by this projects will be published open access to benefit the broader public health and research communities. 'ÄîENDS'Äî",,-99,Colorado State University and UC Davis,40000000,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Bunyaviridae,,,,,,,,,Rift Valley Fever,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Americas,,Data Management and Data Sharing | Innovation,,,United States of America,,"Epidemiological studies | Vaccines research, development and implementation",Disease surveillance & mapping | Phase 1 clinical trial | Phase 2 clinical trial,2023 +P24931,N/A,Emervax - Disease X," - CEPI to provide funding of up to US$2.15 million to advance Emervax Inc's circular RNA platform technology for the development of vaccines against emerging viruses - Funding will contribute to the development of vaccine candidates against high-priority virus families with the potential for Disease X emergence 25 October 2023, OSLO Norway: The Coalition for Epidemic Preparedness Innovations (CEPI) and Emervax Inc, today announced a partnering agreement to advance their circular RNA vaccine technology to develop vaccine candidates against emerging viruses with epidemic and pandemic potential. CEPI will provide up to $2.15 million to optimize the platform and generate data needed to support preclinical proof-of-concept. This funding is part of CEPI's initiative to develop of RNA vaccine platform technologies and vaccine library development against emerging and select endemic infectious diseases. As part of this initiative, CEPI seeks to develop novel RNA platform technologies based on potentially high-impact innovations offering substantial advantages over existing mRNA technologies. It is supporting RNA platform technologies that can be used for the development of vaccine candidates against a specified list of known pathogens and the development of vaccine libraries against high-priority virus families with the potential for Disease X emergence. mRNA vs circular RNA RNA vaccines use the body's own machinery to make antigenic protein rather than injecting the pure antigen directly into the body (an antigen is a foreign substance that induces an immune response). However, existing mRNA vaccines are not stable and require multiple doses. As their name suggests, circular RNA vaccine candidates have a closed-loop structure. This makes them potentially less susceptible to degradation and more stable than mRNA vaccine candidates. The physiological mechanisms that underpin the translation of circular RNA could also lead to increased durability of protein/antigen production in the body after administration, which could result in improved efficacy with lower doses. Emervax is developing methods to improve the purification, scaling up manufacturing of circular RNA with polymeric nanoparticles, and designing & developing of a safe, effective, and potentially thermostable Yellow Fever vaccine. Novel RNA technologies, such as those being developed by Emervax will make up an important part of the proposed Global Vaccine Library: a global repository of vaccine resources, capabilities and data that would maximise epidemic and pandemic preparedness and drive accelerated vaccine development when new viral threats arise. The tools and technologies advanced through this initiative are expected to make a vital contribution to the Global Vaccine Library. The Global Vaccine Library is central to CEPI's 100 Days Mission to develop a vaccine in 10o days after the emergence of a new disease X, giving the world a chance to stop the outbreak of a new infectious disease before it has had time to develop into a pandemic. Enabling equitable access CEPI is committed to enabling equitable access to the vaccines, products and innovations it supports. Through its partnership with CEPI, Emervax has demonstrated its shared commitment to ensuring equitable access to its technology in line with CEPI's Equitable Access Policy, including the potential application of its technology to future vaccine development of interest to CEPI, and a commitment to technology transfer in order to ensure affordable vaccines are available to populations when and where they are needed to end an outbreak or curtail an epidemic or pandemic.",,-99,Emervax,2200000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Flaviviridae | Novel Pathogen,,,,,,,,,Disease X | Other,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,,,Innovation,,,,,"Vaccines research, development and implementation",Vaccine design and administration | Vaccine trial design and infrastructure,2023 +P24933,N/A,Houston Methodist Research Institute - Disease X,"25 January 2024, OSLO Norway: The Coalition for Epidemic Preparedness Innovations (CEPI) is teaming up with leading scientists at the Houston Methodist Research Institute to further develop a promising type of disease-defence technology that could pave the way for new 'Äòcircular RNA'Äô vaccines that are more stable, durable and cost-effective. With CEPI funding of up to $3.8 million, the Houston Methodist vaccinology team aims to advance its 'ÄòcircRNA'Äô platform, a high-impact innovation offering significant potential beyond mRNA vaccines in defending populations against future epidemic and pandemic disease threats. The project is focused on the design and preclinical evaluation of 'ÄòcircRNA'Äô vaccine candidates, initially against Chikungunya 'Äì a CEPI priority pathogen that is a member of the Togaviridae family 'Äì and aims to generate the data necessary to establish preclinical proof of concept for the vaccine platform. RNA vaccine technology, which uses the body'Äôs own machinery to make antigenic protein rather than injecting an antigen into the recipient, has made significant progress in recent years. The most ground-breaking advance came with its validation for the first time during the COVID-19 pandemic, when it was used to develop new vaccines in less than a year that went on to save millions of lives and reduce the number of severe cases of COVID-19. While mRNA vaccines are now expected to play a crucial role in preventing and controlling future outbreaks and pandemics, they have some limitations 'Äì including the potential to provoke local reactions or short-term fever in people who receive them. Relative to other types of vaccine, they are currently expensive to manufacture and require costly and complex cold-chain storage and transportation infrastructure. As the name suggests, circular RNA vaccine technology uses a closed-loop RNA, which could enable vaccine candidates based on it to be more stable and durable than current linear-based mRNA candidates. The technology could also deliver improved efficacy in smaller doses. HMRI'Äôs circRNA platform is still in the early-stages of development, but, if successful, it has the potential to be effective in single-dose regimens, to reduce the amount of RNA needed per dose and to lower the cost of RNA-based vaccines, which could altogether contribute to the accessibility of mRNA vaccines. 'ÄúDespite being once thought of as 'Äòmolecular junk'Äô, recent research has suggested that, with its stable looped structure, 'Äòcircular RNA'Äô could be harnessed for RNA-based medicines, like vaccines'Äù explains Dr In-Kyu-Yoon, Acting Executive Director of Vaccine R&D at CEPI. 'ÄúIf effective, these circRNA vaccines could progress this new scientific era of mRNA vaccinology even further, leveraging not only the speed at which the technology can be designed and tested in response to infectious disease outbreaks but also the potential to create more durable and accessible mRNA vaccines for greater global protection when faced with a deadly disease threat.'Äù CEPI'Äôs investment in HMRI is the latest in its programme to advance novel RNA vaccine platform technologies for emerging and select endemic infectious diseases. The programme aims to evaluate whether the next-generation of RNA technologies could offer substantial advantages over existing mRNA platforms, for example improved immunogenicity, storage, stability, productivity, response time, and cost-of-goods. Improvements to rapid response mRNA technologies may contribute to the 100 Days Mission, a goal backed by leaders of the G7 and G20, to compress vaccine development timelines to 100 days. 'ÄúWe are excited to be working with CEPI on the development of circular RNA vaccine technology to protect the world against emerging viral threats,'Äù said H. Dirk Sostman, M.D. President and CEO of the Houston Methodist Academic Institute. 'ÄúThis effort is led by Dr. John Cooke, director of our Center for RNA Therapeutics, with a team of innovative scientists including Drs. Dan Kiss, Jimmy Gollihar, Kristopher Brannan and Francesca Taraballi, together with our colleagues at University of Texas Medical Branch. Houston Methodist is leading medicine by generating fundamental scientific insights that have transformational effects on human health.'Äù Enabling equitable access to vaccines CEPI and HMRI are committed to enabling equitable access to the outputs of this CEPI-supported programme, in line with CEPI'Äôs Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results including data generated as part of this project will be published open access for the benefit of the global scientific community. 'ÄìENDS'Äì About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of over 30 vaccine candidates against its priority pathogens'ÄîChikungunya virus, Ebola Virus Disease, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and SARS-CoV-2'Äîand is a leading funder of research into broadly protective coronavirus vaccines, which could protect against future variants of COVID-19 as well as other coronaviruses with epidemic and pandemic potential. The organization has also invested in the development of rapid response platforms to develop vaccines against Disease X (the threat of an unknown virus). CEPI has contributed to a number of scientific breakthroughs, including the first ever licensed Chikungunya vaccine and the advancement of the first ever Nipah and Lassa vaccines into Phase 1 trials. The organization played a central role in the global response to COVID-19, supporting the development of one of the world'Äôs largest portfolios of vaccines against SARS-CoV-2, seven of which have been approved for domestic or global use. It also co-led COVAX, the global initiative to deliver fair and equitable access to COVID-19 vaccines, which has delivered approximately 2 billion doses of vaccine to 146 countries around the world. CEPI'Äôs five-year plan for 2022-2026 aims to dramatically reduce or even eliminate the future risk of pandemics and epidemics. Central to the plan is CEPI'Äôs goal to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. Achieving this 'Äò100 Days Mission,'Äô which has been embraced by the G7 and G20, would give the world a fighting chance of containing a future outbreak before it can spread to become a global pandemic. Visit our news page for the latest updates. Follow us via @CEPIvaccines, @DrRHatchett, LinkedIn, and Facebook. About Houston Methodist Houston Methodist is one of the nation'Äôs leading health systems and academic medical centers. The health system consists of eight hospitals: Houston Methodist Hospital, its flagship academic hospital in the Texas Medical Center; six community hospitals; and one long-term acute care hospital throughout the Greater Houston area. Houston Methodist also includes a research institute; a comprehensive residency program; a physician organization; international patient services; freestanding comprehensive care, emergency care and imaging centers; and outpatient facilities. Houston Methodist employs approximately 30,000 people and has had more than 1.9 million outpatient visits and more than 138,000 admissions in 2022. U.S. News & World Report has named Houston Methodist Hospital the Best Hospital in Texas (*In a two-way tie) for 12 years in a row and recognized on the Honor Roll seven times. For more information about Houston Methodist, visit houstonmethodist.org. Follow us on Twitter, Facebook and On Health.",,-99,Houston Methodist Research Institute,3800000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Other,,,,,,,,,Other,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Americas,,,,,United States of America,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2024 +P24935,N/A,Lemonex - Disease X,"04 January 2024, OSLO, Norway and SEOUL, Republic of Korea 'Äì CEPI has partnered with Lemonex Inc. (Lemonex), a biotechnology company in the Republic of Korea, to advance their mRNA drug delivery technology, DegradaBALL¬Æ, which has the potential to both minimise post-mRNA vaccination side effects and improve access to future mRNA vaccines. CEPI is providing Lemonex up to US $4.6 million in funding to evaluate the safety of the DegradaBALL¬Æ mRNA vaccine platform in a Phase I clinical study taking place at Seoul National University Hospital. The funding will also support the development of a freeze-dried formulation which could reduce complex-cold chain vaccine storage requirements and increase the use of mRNA vaccines in the Global South. The new partnership forms part of CEPI'Äôs plan to expand the use of and access to novel RNA innovations for potential use against a future epidemic or pandemic threat, including unknown or as-of-yet unidentified pathogens (Disease X), in alignment with the 100 Days Mission. The ambitious goal spearheaded by CEPI, and embraced by the Republic of Korea as part of their strategic plan against emerging infectious diseases, aims to condense vaccine development to 100 days from virus identification and stop the next pandemic in its tracks. Dr. Richard Hatchett, CEO of CEPI, said: 'ÄúClinically validated for the first time during the COVID-19 pandemic, mRNA vaccines will be critical if we are to accelerate our responses to future infectious disease threats. However, current mRNA vaccines still have limitations in terms of their reactogenicity, cold-chain requirements, and thermostability. Lemonex'Äôs DegradaBALL¬Æ may address these issues and thereby contribute to more equitable responses to future emerging infectious disease outbreaks.'Äù Next-generation vaccine delivery mRNA technologyhas been identified as a pivotal enabler of the 100 Days Mission due to its flexibility as a rapid-response platform on which new vaccine candidates can be designed and quickly made ready for clinical testing and subsequent scale-up, potentially within days from the moment a new viral threat is identified. However, although generally mild, short-lived, and an indicator that the body is responding to a vaccine and building protection, side-effects or reactions induced by current mRNA-based vaccines can occur. Lemonex'Äôs DegradaBALL¬Æ is designed to potentially minimize side effects associated with the use of current lipid nanoparticle (LNP)-mRNA vaccines by increasing the drug residual rate at the administration site and improving the stability of mRNA. Cheolhee Won, CEO of Lemonex Bio, added: 'ÄúUnlike LNP, DegradaBALL¬Æ can be pre-produced even before mRNA synthesis and stored in stock at room temperature. The mRNA-DegradaBALL¬Æ complex can be prepared at the point of use through a simple mixing process of mRNA and DegradaBALL¬Æ. In other words, if DegradaBALL¬Æ is pre-supplied to various parts of the world before a pandemic virus occurs, only the mRNA can be produced in that country and simply mixed and used right before administration. This process can easily resolve the ultra-cold chain issue and production & supply delay issues of LNP-mRNA vaccines. Through the new partnership of CEPI and Lemonex, we plan to develop and supply various types of mRNA vaccine formulation using DegradaBALL¬Æ technology against epidemic and pandemic threats.'Äù Preparing for future threats CEPI'Äôs investment in Lemonex is the latest in its programme to advance novel RNA vaccine platform technologies for emerging and select endemic infectious diseases. The programme aims to evaluate whether the next-generation of RNA technologies could offer substantial advantages over existing platforms, for example improved immunogenicity, storage, stability, productivity, response time, and cost-of-goods. The prototype vaccines, data, and knowledge generated through this programme could make a vital contribution to the proposed Global Vaccine Library. Central to the 100 Days Mission, a Global Vaccine Library is envisaged as a global repository of vaccine resources, capabilities, and data which could be pulled 'Äòoff the shelf'Äô and quickly adapted in response to a future outbreak, accelerating the development of life-saving vaccines. CEPI and Lemonex are committed to enabling equitable access to the outputs of their partnership, in line with CEPI'Äôs Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results including data generated as part of this project will be published open access for the benefit of the global scientific community. The new partnership extends CEPI'Äôs partnerships with Korean-based organisations across the academic, government and pharmaceutical sector. Other partners include SK bioscience, Chungbuk National University, and the International Vaccine Institute (IVI). ENDS Notes to editors About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of over 30 vaccine candidates against its priority pathogens'ÄîChikungunya virus, Ebola Virus Disease, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and SARS-CoV-2'Äîand is a leading funder of research into broadly protective coronavirus vaccines, which could protect against future variants of COVID-19 as well as other coronaviruses with epidemic and pandemic potential. The organization has also invested in the development of rapid response platforms to develop vaccines against Disease X (the threat of an unknown virus). CEPI has contributed to a number of scientific breakthroughs, including the first ever licensed Chikungunya vaccine and the advancement of the first ever Nipah and Lassa vaccines into Phase 1 trials. The organization played a central role in the global response to COVID-19, supporting the development of one of the world'Äôs largest portfolios of vaccines against SARS-CoV-2, seven of which have been approved for domestic or global use. It also co-led COVAX, the global initiative to deliver fair and equitable access to COVID-19 vaccines, which has delivered approximately 2 billion doses of vaccine to 146 countries around the world. CEPI'Äôs five-year plan for 2022-2026 aims to dramatically reduce or even eliminate the future risk of pandemics and epidemics. Central to the plan is CEPI'Äôs goal to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. Achieving this 'Äò100 Days Mission'Äô, which has been embraced by the G7 and G20, would give the world a fighting chance of containing a future outbreak before it can spread to become a global pandemic. Visit our news page for the latest updates. Follow us via @CEPIvaccines, @DrRHatchett, LinkedIn, and Facebook. About Lemonex Inc. Lemonex is a biotechnology company pioneering safe and effective mRNA medicine and cancer immunotherapy based on innovative non-viral drug delivery platform technology. The core drug delivery system (DDS) technology, DegradaBALL¬Æ, is a novel porous nanoparticle-based global first-in-class drug delivery system that maximizes therapeutic efficacy and minimizes systemic side effects. DegradaBALL¬Æ, a modular next-generation drug delivery technology is Lemonex'Äôs original technology, which enables in vivo delivery by loading various new drug candidates inside particles, and which is optimized for the development of gene therapies and immuno-oncology drugs. Recently, nano-drug delivery technologies have attracted a lot of attention; DegradaBALL¬Æ is the most advanced nanotechnology-based drug delivery system that can overcome the limitations of LNPs. DegradaBALL¬Æ can solve cold-chain issues of current LNPs and maintain its stability at room temperature. Lemonex is developing various competitive new drug candidates based on the DegradaBALL¬Æ, such as siRNA gene therapy, mRNA vaccine, dual-acting RNA immunotherapy, and biobetter by applying the DegradaBALL¬Æ drug delivery platform. Lemonex confirmed the safety and tolerability of DegradaBALL¬Æ in healthy subjects through the phase I clinical trial of the LEM-S401, an siRNA-DegradaBALL¬Æ drug candidate. Visit our news page for the latest updates. Follow us via @cheolheewon, @dalheemin, and Facebook",,-99,Lemonex,4900000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,"Clinical Trial, Phase I",Novel Pathogen,,,,,,,,,Disease X,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,,,Innovation,,,,,"Vaccines research, development and implementation",Vaccine design and administration,2024 +P24945,N/A,University of Oxford and Barinthus - MERS,"OSLO, Norway/ OXFORD, UK, 21 December 2023 - A partnership between CEPI, Barinthus Biotherapeutics and the University of Oxford, the scientists behind one of the life-saving COVID-19 vaccines, aims to fast-track the development of a potential vaccine known as VTP-500 for the prevention of Middle East Respiratory Syndrome, the often fatal disease caused by the MERS coronavirus. The project will see CEPI, Barinthus Bio, an Oxfordshire-based clinical-stage biopharmaceutical company, and the University of Oxford together take a MERS vaccine from early development through Phase II clinical trials and, if the Phase II clinical trials are successful, on into the development of an investigational ready reserve* of 100,000 doses to be rapidly deployed in a clinical trial setting in the event of a substantial outbreak. ""Coronaviruses are one of the most urgent infectious disease threats the world faces, so it's vital that we get on with developing medical defences against this particularly deadly one 'Äî MERS,"" said Dr Richard Hatchett, CEPI's Chief Executive Officer. ""With this project, we will both advance scientific understanding of the coronavirus family as a whole, and at the same time bolster humanity's ability to respond to an ever-present epidemic threat."" ""The COVID-19 pandemic showed us the critical importance of vaccines in saving millions of lives around the world,"" said Professor Dame Sarah Gilbert, Pandemic Sciences Institute, University of Oxford. ""We had a head-start in our development of the Oxford/AstraZeneca COVID-19 vaccine, thanks to the many years already spent researching a vaccine for another coronavirus, MERS. This new partnership will help ensure the world is better prepared with vaccines for future outbreaks."" ""We are thrilled to be working with the University of Oxford and CEPI on the development of this important vaccine candidate,"" said Bill Enright, Barinthus Bio's Chief Executive Officer. ""There is an active need for a MERS vaccine for at-risk populations and travellers in the Middle East. As we observed during the COVID-19 pandemic, it is critical to ensure we have the necessary countermeasures in place to protect people around the world from deadly pathogens such as MERS which have the potential for future outbreaks."" The three-way partnership, which awards up to $34.8 million to Barinthus Bio in addition to funds previously committed to the University of Oxford, builds on the early-stage development of VTP-500, which is based on the same viral vector platform technology as the licensed Oxford-AstraZeneca COVID-19 vaccine, Vaxzevria. VTP-500 has already completed Phase I clinical trials in Britain and Saudi Arabia, and the University of Oxford is now conducting a CEPI-funded extension to the Phase I trial in the UK to assess vaccination of older adults, the age group most in need of this vaccine. The VTP-500 programme was awarded PRIME designation earlier in December by the European Medicines Agency (EMA). MERS is a severe respiratory infection caused by MERS-CoV, a coronavirus that was first identified in 2012 in Saudi Arabia. It has caused more than 2,600 human infections in at least 27 countries since it first emerged, and it has a case-fatality rate of more than 35 percent. There are as yet no licensed vaccines or treatments for MERS. Enabling equitable access to VTP-500 CEPI, the University of Oxford and Barinthus Bio are committed to enabling equitable access to VTP-500 in line with CEPI's Equitable Access Policy so the vaccine is first available to populations when and where it is needed to end an outbreak or curtail an epidemic, regardless of ability to pay. If the vaccine is successful in Phase II trials, CEPI will support production of an investigational ready reserve of 100,000 doses which can be rapidly deployed in a clinical trial setting in response to an outbreak of MERS. CEPI also has the ability to support technology transfer to an additional appropriate regional manufacturer to enable supply for low- and middle-income countries. The vaccine will be made available to low- and middle-income countries at a price no higher than the cost of manufacturing plus 10 percent. ENDS Notes to Editors *An investigational ready reserve is an agreed quantity of investigational doses for potential use in a clinical trial. EMA PRIME Designation Due to VTP-500's potential in significantly addressing the unmet need for MERS, the EMA has confirmed support for the program through the PRIME designation. PRIME enhances support for the development of medicines that target an unmet medical need, offering early and proactive support to medicine developers to optimise the generation of robust data on a medicine's benefits and risks and enable accelerated assessment of medicines applications. Emergency Use The agreement refers to supply in Outbreaks defined as a Public Health Emergency of International Concern declared by WHO, or a public health emergency on a national or regional scale declared by one or more public health agencies. About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of over 30 vaccine candidates against its priority pathogens'ÄîChikungunya virus, Ebola Virus Disease, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and SARS-CoV-2'Äîand is a leading funder of research into broadly protective coronavirus vaccines, which could protect against future variants of COVID-19 as well as other coronaviruses with epidemic and pandemic potential. The organization has also invested in the development of rapid response platforms to develop vaccines against Disease X (the threat of an unknown virus). CEPI has contributed to a number of scientific breakthroughs, including the first Phase 3 trial of a Chikungunya vaccine and the advancement of the first ever Nipah and Lassa vaccines into Phase I trials. The organization played a central role in the global response to COVID-19, supporting the development of one of the world's largest portfolios of vaccines against SARS-CoV-2, seven of which have been approved for domestic or global use. It also co-led COVAX, the global initiative to deliver fair and equitable access to COVID-19 vaccines, which has delivered approximately 2 billion doses of vaccine to 146 countries around the world. CEPI's five-year plan for 2022-2026 aims to dramatically reduce or even eliminate the future risk of pandemics and epidemics. Central to the plan is CEPI's goal to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. Achieving this 'Äò100 Days Mission', which has been embraced by the G7 and G20, would give the world a fighting chance of containing a future outbreak before it can spread to become a global pandemic. Visit our news page for the latest updates. Follow us via @CEPIvaccines, @DrRHatchett, LinkedIn, and Facebook. About Barinthus Biotherapeutics Barinthus Bio is a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity, and cancer. Helping people living with serious diseases and their families is the guiding principle at the heart of Barinthus Bio. With a broad pipeline, built around three proprietary platform technologies: ChAdOx, MVA and SNAP; Barinthus Bio is advancing a pipeline of five product candidates across a diverse range of therapeutic areas, including: VTP-300, an immunotherapeutic candidate designed as a potential component of a functional cure for chronic HBV infection; VTP-200, a non-surgical product candidate for persistent high-risk human papillomavirus (HPV); VTP-1000, an autoimmune candidate designed to utilize the SNAP-Tolerance Immunotherapy (TI) platform to treat patients with celiac disease; VTP-850, a second-generation immunotherapeutic candidate designed to treat recurrent prostate cancer; and VTP-1100, a preclinical cancer candidate designed to utilize the SNAP-Cancer Immunotherapy (CI) platform to treat patients with HPV-related cancer. Barinthus Bio's proven scientific expertise, diverse portfolio and focus on pipeline development uniquely positions the company to navigate towards delivering treatments for people with infectious diseases, autoimmunity and cancers that have a significant impact on their everyday lives. For more information, visit www.barinthusbio.com. Barinthus Bio Forward-Looking Statements This press release contains forward-looking statements regarding Barinthus Bio within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, which can generally be identified as such by use of the words ""may,will,"" ""plan,"" ""forward,"" ""encouraging,"" ""believe,"" ""potential,"" and similar expressions, although not all forward-looking statements contain these identifying words. These forward-looking statements include, without limitation, express or implied statements regarding the Company's future expectations, plans and prospects, including the potential benefits of VTP-500 for the treatment of MERS. Any forward-looking statements in this press release are based on Barinthus Bio management's current expectations and beliefs and are subject to numerous risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the success, cost and timing of Barinthus Bio's pipeline development activities and planned and ongoing clinical trials, Barinthus Bio's ability to execute on its strategy, regulatory developments, the risk that Barinthus Bio may not realize the benefits related to its rebranding and name change, Barinthus Bio's ability to fund its operations and access capital, global economic uncertainty, including disruptions in the banking industry, the conflict in Ukraine, and the conflict in Israel and Gaza, and other risks identified in Barinthus Bio's filings with the Securities and Exchange Commission (the ""SEC""), including its Annual Report on Form 10-K for the year ended December 31, 2022, its Quarterly Reports on Form 10-Q and subsequent filings with the SEC. Barinthus Bio cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Barinthus Bio expressly disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. About Pandemic Science Institute, University of Oxford The Pandemic Sciences Institute at the University of Oxford is a research institute with a mission to discover, create and enable practical solutions to infectious disease threats worldwide. The Institute is hosted by the University's Nuffield Department of Medicine. Visit our website and Follow us on X (formerly Twitter). Media contacts CEPI E: press@cepi.net T: +44 7387 055214 Barinthus Biotherapeutics Investor Contacts: Christopher M. Calabrese Managing Director LifeSci Advisors +1 917-680-5608 ccalabrese@lifesciadvisors.com Kevin Gardner Managing Director LifeSci Advisors +1 617-283-2856 kgardner@lifesciadvisors.com Media contact: Audra Friis Sam Brown, Inc. +1 917-519-9577 audrafriis@sambrown.com Company contact: Jonothan Blackbourn IR & PR Manager Barinthus Biotherapeutics ir@barinthusbio.com University of Oxford E: news.office@admin.ox.ac.uk T: +44 1865 280528",,-99,University of Oxford and Barinthus,19000000,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Europe,,,,,United Kingdom,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial,2023 +P24947,N/A,Valneva - Chikungunya,"As Valneva's Chikungunya vaccine candidate gains FDA approval, CEPI's CEO Dr Richard Hatchett outlines how CEPI/EU funding has been critical to accelerating access for endemic countries. A vaccine against Chikungunya has secured regulatory approval for the first time. Licensure of Valneva's live-attenuated vaccine candidate (known as IXCHIQ) by the US Food and Drug Administration (FDA) is a huge leap forward in the fight against this debilitating disease. The next step is even more important: making this vaccine accessible to those living in endemic countries who are most at risk from the disease. Investing to accelerate access in endemic countries CEPI's funding for IXCHIQ, supported by the European Union's Horizon 2020 Programme, is first and foremost intended to accelerate endemic country access to a vaccine that, prior to CEPI's involvement, had been developed and funded by Valneva predominantly as a vaccine for travelers from high-income countries. In recent years the EU's Health Emergency Preparedness and Response Authority (HERA) and CEPI have developed a strong partnership with a shared focus on preparedness and response to serious health threats. CEPI/ EU investment is designed specifically to enable access to the vaccine by accelerating regulatory approval in endemic regions and supporting technology transfer to a Global South vaccine manufacturer to facilitate access to the vaccine in Low- and Middle-Income Countries (LMICs) at affordable pricing. Valneva has demonstrated its commitment to access by partnering with us, and Brazil's Instituto Butantan, to advance both of these goals. The vaccine candidate was already in late-stage development at the time of CEPI/ EU investment in 2019. It was the most advanced Chikungunya vaccine candidate in the field, it had extremely promising data, and as a single-dose vaccine it was well-suited for use in outbreak responses and in low-resource settings. However, we knew when we made the decision to invest in the vaccine that licensure would come later in LMICs than it would in high income countries because the vaccine was already following a regulatory pathway tailored towards licensure with stringent regulatory authorities in the USA and Europe. It would take additional time to generate the data needed for regulatory approval in endemic regions, and to complete the technology transfer to a Global South manufacturer that was needed to achieve an accessible and affordable vaccine. Nonetheless, the quality of the vaccine candidate and Valneva's willingness to support vaccine access in endemic countries convinced us to invest in their promising candidate. Without the support from CEPI and the European Union's Horizon 2020 Programme this vaccine might have remained a product principally targeting travellers from the Global North and health inequities would have been perpetuated. Our continued collaboration with HERA, along with CEPI/ EU investment, will ensure that the vaccine is made available globally more rapidly than would have occurred otherwise. Achieving sustainable and affordable access To date, CEPI and the EU have committed up to $24.6 million to enable access to IXCHIQ in endemic countries. In the complex and costly field of vaccine R&D this is a relatively modest investment, and a fraction of the overall development cost for this vaccine, but it is one that is destined to have a significant impact for those living in countries with the highest burden of disease. This funding primarily supports the following activities: - Technology transfer of Drug Product to Valneva's partner in Brazil, Instituto Butantan, who will manufacture and market the vaccine in LMICs. This will enable sustainable, reliable, and affordable access to the vaccine for endemic countries in the future. - Late-stage studies designed to generate data that will contribute to future regulatory approval in Brazil, a country which experiences a high burden of Chikungunya disease. This includes a phase 3 clinical trial in adolescents in Brazil, now nearing completion, which will expand access to younger people and support regulatory approval in Brazil and other countries in Latin America. - Access to an emergency stockpile of 200,000 vaccine doses which, at CEPI's direction, can be supplied to affected countries free of charge to help control disease outbreaks until the Instituto Butantan-produced vaccine becomes available. These activities, in combination, will facilitate vaccine access in endemic countries in the short-term and medium-term. In the longer-term, there are still crucial R&D and policy questions that need to be answered to support the rollout of Chikungunya vaccines 'Äî whether Valneva's or other CEPI-backed candidates 'Äî in endemic countries. A recent CEPI Call for Proposals, also backed by the European Union, will help to address these questions by funding phase 4 real-world effectiveness studies, long-term evaluations of safety and immunogenicity, and further trials will help to expand access to vulnerable groups including pregnant women, children, and people who are immunocompromised. In the meantime, CEPI will continue to work with PAHO and regulators in affected countries to discuss routes to licensure and prepare for the availability of Chikungunya vaccines. So all of us will now take a moment to celebrate this historic milestone and to congratulate our colleagues at Valneva on a historic achievement. We'll then get on with the urgent task of making sure that those who most need a Chikungunya vaccine can access one.",,-99,Valneva SE,24600000,Human Populations | Other,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Other,,,,,,,,,Other,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Europe,,,,,France,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies | Vaccine design and administration | Vaccine trial design and infrastructure,2023 +P24948,N/A,Wageningen Bioveterinary Research - Rift Valley fever,"'Ä¢ CEPI to invest up to $25.9 million, with support from the EU, in trials in East Africa to assess a vaccine candidate against Rift Valley Fever (RVF) in people most at risk of infection 'Ä¢ Climate change is causing the potentially deadly mosquito-borne virus to expand its reach, thereby increasing the threat it poses to the lives and livelihoods of affected populations 'Ä¢ New Phase I/IIa trials for RVF vaccine candidate will help to accelerate urgent need for a protective vaccine 10 October 2023, OSLO, Norway/ WAGENINGEN, Netherlands: The Coalition for Epidemic Preparedness Innovations (CEPI) is expanding its partnership with Wageningen Bioveterinary Research (WBVR) to advance WBVR's vaccine candidate against Rift Valley fever (RVF) through a multi-site Phase I/IIa clinical trial. Subject to regulatory and ethical approvals, the anticipated trials are scheduled to begin in 2025 in Kenya and Uganda, two countries where the mosquito-borne disease poses a significant threat to the lives and livelihoods of people in rural communities. Backed with up to US$25.9 million in funding from CEPI, with support from the European Union's Horizon Europe programme, the studies will be the first to assess the safety and immunogenicity of WBVR's RVF vaccine in countries where RVF is endemic. WBVR's live-attenuated vaccine known as hRVFV-4s, and being further developed under Wageningen spin-off Bunyavax, is currently being evaluated in a Phase I clinical trial in Belgium under a previous CEPI/ EU grant. In addition to the anticipated trials in Kenya and Uganda, CEPI will fund an extension of the ongoing Phase I study to assess immunogenicity up to 24 months; manufacturing of clinical trial materials; epidemiological research to assess the burden of infection and the risk of 'Äòspillover' transmission from animals to humans in Kenya and Uganda; and regulatory engagement, including a strategy for achieving licensure of the vaccine. The work will be a combined effort of WBVR with consortium partners Batavia Biosciences BV, Bunyavax BV, CR2O BV, University of Veterinary Medicine Hannover, and Integrum Scientific, LLC. Dr Richard Hatchett, CEO of CEPI, said: ""Climate change and extreme weather are expanding the range of potential Rift Valley fever outbreaks and increasing its potential to cause devastation to the lives and livelihoods of people in rural communities in Africa and beyond. We urgently need a vaccine to strengthen our defenses against this emerging disease and protect the vulnerable populations who are exposed to it. Through CEPI's expanded partnership with Wageningen Bioveterinary Research, supported by EU funding, we will generate crucial data needed to accelerate the development of this much-needed vaccine, helping to bring a protective solution closer to the growing number of people who may be affected by this potentially deadly disease."" Marc Lema√Ætre, Director-General for Research and Innovation, European Commission, said: ""With the memories of the recent pandemic still fresh in our minds, we know how important it is to invest in research to prevent and control the threat from infectious diseases. An effective vaccine against Rift Valley Fever would go a long way to prevent more frequent and deadly outbreaks, with all the serious public health and socioeconomic consequences that we see today. I am pleased to see that these essential research projects can now take off with the steadfast support of the European Union and Horizon Europe, through our great collaboration with CEPI. The EU and its Member States have been among the largest contributors to CEPI since its inception. From the EU Framework Programmes for Research and Innovation, we have provided more than EUR 240 million since 2017 and we are proud of the great scientific progress the strong partnership with CEPI has produced on Ebola, Chikungunya, Rift Valley Fever, and COVID-19 so far. I am confident that the projects starting today will bring us even closer to an effective vaccine against Rift Valley Fever."" Dr. Paul Wichgers Schreur, researcher at WBVR, developer of the hRVFV-4s vaccine and leader of the consortium, said: ""With promising results from the Phase I clinical trial in Belgium and the continuation of the collaboration with CEPI we are taking a huge step in reducing the burden of disease in Africa where the virus continues to affect both animals and humans. In addition, a RVF vaccine will contribute to preparedness for potential virus emergence in yet unaffected regions like Europe in which susceptible mosquito species are currently expanding territory."" Rift Valley fever: A climate-driven disease with epidemic potential RVF is a potentially deadly virus which can spread to people either through mosquito bites or through contact with infected livestock. The disease can cause severe symptoms such as encephalitis and hemorrhaging and kills around 1 percent of all those it infects. RVF is also profoundly destructive for the livelihoods of those in rural areas where outbreaks occur and often results in large-scale losses of livestock. Because of its impact on both people and animals, RVF is a prime candidate for a 'ÄòOne Health' approach to disease control. No safe and effective human vaccines or treatments have yet been approved for use against RVF, so their development is considered a top priority by both the Africa CDC and the World Health Organization's R&D Blueprint team. RVF was first identified in Kenya's Rift Valley, but in recent decades has steadily extended its reach across much of Africa and parts of the Middle East, putting more people in more countries at risk of infection. Outbreaks of RVF have been consistently linked with intense periods of rainfall and flooding - including those caused by the El Ni√±o phenomenon which has recently returned after a seven year absence. Heavy rains provide ideal conditions for RVF-infected mosquitoes to breed and hatch. As climate change persists, expanding the range of mosquitoes and increasing the likelihood of extreme weather events such as flooding, there is a risk that RVF outbreaks will become more frequent and widespread making the development of a protective human vaccine all the more urgent. Enabling equitable access to RVF vaccines RVF primarily impacts rural and pastoral communities living in low- and middle-income countries in East Africa. CEPI and the WBVR-led consortium are committed to enabling equitable access to RVF vaccines to the populations who need them, in line with CEPI's Equitable Access Policy. This includes planning for the potential development of investigational stockpiles for use in outbreak situations, agreeing to an affordable pricing mechanism such as Cost of Goods +%, and endeavouring to manufacture the vaccine at geographically dispersed manufacturing sites close to where outbreaks may occur in order to minimise supply risks. In addition, the clinical trial and epidemiological data generated by this project will be published open access to benefit the broader public health and research communities. This project is being awarded funds under a CEPI Call for Proposals designed to support RVF vaccine candidates through clinical trials in endemic areas, which is supported by EUR35 million provided by the European Union's Horizon Europe programme. --ENDS--",,-99,Wageningen Bioveterinary Research,38400000,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II",Bunyaviridae,,,,,,,,,Rift Valley Fever,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Europe,,,,,Netherlands,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial | Adverse events associated with immunization,2023 +P24949,16LW0450,KMUi-Biomedicine-2: AdaptInnate Optimisation (AdInOpt) - Improvement of the anti-tumour T cell response by arenavirus virotherapy,,,2025,Universitätsklinikum Düsseldorf,301845.52,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Arenaviridae,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P24950,16LW0449,KMUi-Biomedicine-2: AdaptInnate Optimisation (AdInOpt) - Arenavirus-mediated enhancement of T cell-based tumour therapies,,,2025,Universitätsklinikum Essen,242743.08,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Arenaviridae,,,,,,,,,Lassa fever,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P24951,16LW0448K,KMUi-Biomedicine-2: AdaptInnate Optimisation (AdInOpt) - Optimisation in the molecule,,,2025,ABALOS THERAPEUTICS GmbH,728643.81,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P24952,01KI2019,BULITA - The multifunctional bunyavirus L protein as an inhibitor target,,,2025,Bernhard-Nocht-Institut für Tropenmedizin (BNITM),2430231.07,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",,2020 +P24953,HZI2021Z38,Vaccine platform recombinant measles viruses,,,2026,Paul-Ehrlich-Institut Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel,601096.08,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P24954,16GW0261,Target validation: Validation of the RNA helicase eIF4A as a broad-spectrum antiviral target (HELIATAR) - Possible development of resistance and elucidation of the resistance mechanisms involved,,,2022,Justus-Liebig-Universität Gießen,248531.44,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P24955,01ER1801AX,NAKO Health Study - Supplementary funding,,,2020,NAKO e.V.,3994352.13,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24956,HZI2020Z35,MeV-derived vaccine candidates with protective effect against COVID-20,,,2021,Paul-Ehrlich-Institut Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel,90719.83,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Vaccines research, development and implementation",,2020 +P24957,05K20CB1,Collaborative project 05K2020 STOP-CORONA: Development of inhibitors against the major protease of the coronavirus SARS-CoV-2 based on crystallographic fragment screening (subproject 1).,,,2022,Helmholtz-Zentrum Berlin für Materialien und Energie Gesellschaft mit beschränkter Haftung,119900,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2020 +P24958,16SV8569,ProteCT: Protection against the coronavirus through telemedicine,,,2021,Technische Universität München,282047.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,,,2020 +P24959,05K20BI1,Collaborative project 05K2020 STOP-CORONA: Development of inhibitors against the major protease of the coronavirus SARS-CoV-2 based on crystallographic fragment screening (subproject 2).,,,2020,Bernhard-Nocht-Institut für Tropenmedizin (BNITM),100280,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2020 +P24960,01IS20S07,Software Sprint - individual project: Collabovid - Collaboration platform for scientific exchange on coronavirus publications,,,2020,"Jonas Dippel, Yannic Lieder, Eike Niehs, Michael Perk, Moritz Pfister GbR",51754.29,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24961,05K20FL1,Collaborative project 05K2020 STOP-CORONA: Development of inhibitors against the major protease of the coronavirus SARS-CoV-2 based on crystallographic fragment screening (subproject 3).,,,2022,Universität zu Lübeck,490291.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2020 +P24962,16SV8568,ProteCT: Protection against the coronavirus through telemedicine,,,2021,Klinikum rechts der Isar der Technischen Universität München,425804.05,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Infection prevention and control,,2020 +P24963,16SV8567,ProteCT: Protection against the coronavirus through telemedicine,,,2021,FRANKA EMIKA GmbH,927925.35,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Infection prevention and control,,2020 +P24964,01KI2006D,RAPID: Efficiency of proteolytic activation of respiratory viruses as a marker for pandemic potential (subproject P4-DPZ).,"The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections. The pathogen was discovered in 2012 during a fatal viral pneumonia in Saudi Arabia. Specific treatment options do not yet exist. Up to 30 percent of those infected die. The infection is usually rare. It is usually acquired through contact with dromedaries, which are one of the main livestock in the Middle East and parts of Africa. However, human-to-human transmission does occur and leads to larger outbreaks. The virus is not yet well adapted to humans as hosts. However, there are fears of mutations that could lead to a higher risk of infection and subsequently a pandemic. MERS-CoV is therefore currently one of the most threatening, so-called ""pre-pandemic"" infectious pathogens. In order to combat pre-pandemic pathogens efficiently, it is essential that the public health service obtains solid assessments of outbreak progressions. The research consortium therefore aims to use the example of MERS-CoV to address constraints and research questions for the public health service. In particular, approaches are to be developed that enable science and public health to detect the outbreak of pre-pandemic viruses earlier and prevent their transformation into pandemic pathogens. In addition, a vaccine for host animals and humans is to be developed in collaboration with partners in Saudi Arabia. The network is part of the National Research Network on Zoonotic Infectious Diseases. In particular, the ""One Health"" approach (simultaneous consideration of human and veterinary aspects) and the transfer of results into the application of the public health service are being pursued.",,2022,Deutsches Primatenzentrum Gesellschaft mit beschränkter Haftung - Leibniz-Institut für Primatenforschung,135143.14,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Disease transmission dynamics | Pre-clinical studies | Approaches to public health interventions,2020 +P24965,01IS20S26,Software Sprint - Individual projects: ImmunHelden - Immunity as a resource,,,2020,ImmunHelden Stefan Gränitz Christine Eichkorn Heike Borst Sonja Döring Saskia Kools GbR,52703.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24966,01KI20702,MSarsCoV2 - Development of a recombinant viral vector vaccine for active immunization of at-risk groups against clinical SARS-2 coronavirus infections.,"The MSarsCoV2 vaccine project involves the preclinical and clinical development of a recombinant viral MVA vector vaccine against covid-19 and focuses in particular on particularly vulnerable target groups (very old or pre-diseased people). For active immunisation, a carrier virus that is not capable of replication in humans and has been tested for a long time is used, which produces the spike protein of the SARS 2 coronavirus in the vaccinated human and induces the formation of neutralising antibodies as well as a cellular (T-cell) immune response. The vaccine vector was developed at Ludwig-Maximilians-Universität (LMU) Munich. The LMU is substantially involved in the clinical development with other sites of the German Center for Infection Research (DZIF). Data already available speak for the immunological efficacy. Clinical development is being carried out with multi-centre clinical trials at partner institutions in Germany and abroad and is intended to create the prerequisite for approval of the vaccine. In parallel, the manufacturing technology for commercial production is being optimised and expanded at IDT Biologika GmbH. Innovative analytical technologies will support rapid production and testing. IDT Biologika GmbH will increase the capacities for the production of the active ingredient and sterile filling to ensure the provision of the required vaccine doses for the demands.",,2021,IDT Biologika GmbH,21554065.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Phase 3 clinical trial | Vaccine design and administration,2020 +P24967,03COV21A,"CORONA - EPI-Dx - Epidemiological study on peptide signatures, immunity, genetic predisposition, and changes in SARS-CoV-2; TP1.",,,2023,ATLAS Biolabs GmbH,476741.04,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease surveillance & mapping | Prognostic factors for disease severity",2021 +P24968,03COV21B,"CORONA - EPI-Dx - Epidemiological study on peptide signatures, immunity, genetic predisposition, and changes in SARS-CoV-2; TP2.",,,2022,in.vent Diagnostica GmbH,148929.24,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease surveillance & mapping | Prognostic factors for disease severity",2021 +P24969,03COV10E,CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and compatibility for humans; TP5: Development of remote UVC LEDs and emitters based thereon for irradiation of the coronavirus SARS-CoV-2.,,,2023,"Ferdinand-Braun-Institut gGmbH, Leibniz- Institut für Höchstfrequenztechnik",1145029.57,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P24971,13GW0544E,Collaborative project: Biofunctional filter material development for medical respiratory protection (PathoClear) - Subproject: Synthesis of biofunctional polymer coatings for the adsorption and deactivation of viruses,,,2022,Freie Universität Berlin,178516.31,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P24972,13GW0544A,Collaborative project: Biofunctional filter material development for medical respiratory protection (PathoClear) - Subproject: Validation of material research using mouth-nose protection prototypes,,,2022,Impact Products GmbH,0,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P24973,HZI2021Z45,Application of recombinant bacterial membrane vesicles (BMVs) in vaccination against MERSCoV and H1N1 influenza virus.,,,2022,Paul-Ehrlich-Institut Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel,51240,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Orthomyxoviridae,H1,H1N1,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Vaccines research, development and implementation",,2021 +P24977,13GW0604E,"KMU-innovativ - Collaborative project: Rapid test for neutralizing antibodies against SARS-CoV-2 (NanoNeutVir) - Subproject: Research, characterization and production of a complement trigger",,,2025,Philipps-Universität Marburg,68385,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P24978,13GW0604A,KMU-innovativ - Collaborative project: Rapid test for neutralising antibodies against SARS-CoV-2 (NanoNeutVir) - Sub-project: Research and optimisation of assay components for the rapid test and research-accompanying testing of the demonstrators,,,2025,Mikrogen GmbH,240823.35,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics | Immunity,2022 +P24979,13GW0604B,"KMU-innovativ - Collaborative project: Rapid test for neutralising antibodies against SARS-CoV-2 (NanoNeutVir) - Sub-project: Research, optimisation and establishment of the manufacturing process for the assay components",,,2025,MicroCoat Biotechnologie GmbH,167456.68,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P24980,16LW0416,GBi4S: Rational engineering of post-translational modifications of proteins for novel vaccines and medical applications (Glycodynamix),,,2024,Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.,103820.64,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Vaccines research, development and implementation",,2023 +P24981,01ZX1604D,CAPSyS - Systems medicine of community-acquired pneumonia: Subproject 2-Depth characterization of COVID-19 patients and further analyses in existing cohorts.,,,2022,Universitätsklinikum Jena,372110.41,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,,2020 +P24982,01DK20087,Collaborative project: Real-time analysis of global measures to combat the spread of the new corona pathogen and identification of best practices to strengthen the health care system in Iran and Germany,,,2021,AKFS Akademie der Katastrophenforschungsstelle gGmbH,164254.41,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Health Systems Research,Impact/ effectiveness of control measures | Health service delivery,2020 +P24983,031L0302C,"MODUS-COVID: Model-based investigation of school closures and other measures to contain Covid-19 - Subproject 3: Parameter estimates, detailed contagion dynamics and high performance computing",,,2025,Zuse-Institut Berlin,487967.61,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +P24984,031L0302A,"MODUS-COVID: Model-based investigation of school closures and other measures to contain Covid-19 - Subproject 1: Urban and regional simulation based on data-supported, synthetic movement profiles",,,2025,Technische Universität Berlin,2822600.77,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2020 +P24985,01KI2098A,"OnCoVID - Management in oncology during the COVID-19 pandemic - ethical, legal and health economic implications - TP1: Analysis of decision conflicts, TP2: Outcome effects",,,2021,Medizinische Hochschule Hannover (MHH),442869.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24986,01KI20143A,COVID-Protect - Efficacy of Nrf2 activators for the prevention of cell damage in COVID-19 - Subproject screening of Nrf2 activators.,"COVID-19 poses a great challenge for humanity and the health system whose functionality is of great importance. Due to the rapid spread of COVID-19, protective measures are essential. Healthcare workers are at forefront of exposure to infected and undiagnosed COVID-19 cases. Regardless of the pandemic, patients, especially the chronic ill, need medical advice. In this case, protection of employees in health care system is linked to specific requirements to avoid contagion and staff downtime and to ensure the functionality of the basic health care system. Recommendations for personal protective equipment can vary between public health authorities, which can contribute to uncertainty among healthcare workers. Knowledge is limited and reports of experiences are essential.There is a lack of direct information on experience, attitudes and the infection prevention of healthcare workers. Elicitations of health system worker´s experience, attitudes and personal protection of the use of masks, hygiene measures and vaccinations are required. The aim of this study is to determine the protection situation of general practitioners and employees of nursing homes. The knowledge and the experiences of practitioner´s protection help to uncover strengths and weaknesses and for guiding evidence-based protective measures in healthcare settings. Method: This mixed-method study will examine the protection situation of general practitioners and employees of nursing homes by executing semi-structured interviews and a survey.",,2021,Johann Wolfgang Goethe-Universität Frankfurt am Main,136096.98,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Infection prevention and control | Policies for public health, disease control & community resilience",IPC in health care settings | Approaches to public health interventions,2020 +P24987,01KI20143C,COVID-Protect - Efficacy of Nrf2 activators for the prevention of cell damage in COVID-19 - Toxicity and efficacy studies subproject.,"COVID-19 poses a great challenge for humanity and the health system whose functionality is of great importance. Due to the rapid spread of COVID-19, protective measures are essential. Healthcare workers are at forefront of exposure to infected and undiagnosed COVID-19 cases. Regardless of the pandemic, patients, especially the chronic ill, need medical advice. In this case, protection of employees in health care system is linked to specific requirements to avoid contagion and staff downtime and to ensure the functionality of the basic health care system. Recommendations for personal protective equipment can vary between public health authorities, which can contribute to uncertainty among healthcare workers. Knowledge is limited and reports of experiences are essential.There is a lack of direct information on experience, attitudes and the infection prevention of healthcare workers. Elicitations of health system worker´s experience, attitudes and personal protection of the use of masks, hygiene measures and vaccinations are required. The aim of this study is to determine the protection situation of general practitioners and employees of nursing homes. The knowledge and the experiences of practitioner´s protection help to uncover strengths and weaknesses and for guiding evidence-based protective measures in healthcare settings. Method: This mixed-method study will examine the protection situation of general practitioners and employees of nursing homes by executing semi-structured interviews and a survey.",,2022,Helmholtz-Zentrum für Infektionsforschung GmbH,292391.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Infection prevention and control | Policies for public health, disease control & community resilience",IPC in health care settings | Approaches to public health interventions,2020 +P24988,01KI20143B,COVID-PROTECT - Efficacy of Nrf2 activators for the prevention of cell damage in COVID-19 - Subproject Production of airway epithelial cells from human induced pluripotent stem cells.,"COVID-19 poses a great challenge for humanity and the health system whose functionality is of great importance. Due to the rapid spread of COVID-19, protective measures are essential. Healthcare workers are at forefront of exposure to infected and undiagnosed COVID-19 cases. Regardless of the pandemic, patients, especially the chronic ill, need medical advice. In this case, protection of employees in health care system is linked to specific requirements to avoid contagion and staff downtime and to ensure the functionality of the basic health care system. Recommendations for personal protective equipment can vary between public health authorities, which can contribute to uncertainty among healthcare workers. Knowledge is limited and reports of experiences are essential.There is a lack of direct information on experience, attitudes and the infection prevention of healthcare workers. Elicitations of health system worker´s experience, attitudes and personal protection of the use of masks, hygiene measures and vaccinations are required. The aim of this study is to determine the protection situation of general practitioners and employees of nursing homes. The knowledge and the experiences of practitioner´s protection help to uncover strengths and weaknesses and for guiding evidence-based protective measures in healthcare settings. Method: This mixed-method study will examine the protection situation of general practitioners and employees of nursing homes by executing semi-structured interviews and a survey.",,2021,Medizinische Hochschule Hannover (MHH),146326.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Infection prevention and control | Policies for public health, disease control & community resilience",IPC in health care settings | Approaches to public health interventions,2020 +P24989,01KI2098B,"OnCoVID - Management in oncology during the COVID-19 pandemic - ethical, legal and health economic implications - TP3 Ethical and legal aspects",,,2021,Leibniz Universität Hannover,86437.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P24990,01IS20S30,Software Sprint - Individual project: match4healthcare - Further development of the 0pen source platform Match4healthcare,,,2020,"Behrens, Bischoff, Sauder, Sievers, Yuan, Zacharias GbR",51634.7,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,Health service delivery,2020 +P24992,01KI20500,"Understand-ELSED - Public perception of ethical, legal and socio-economic dimensions of the COVID-19 outbreak",,,2022,Institut für psychologische Forschung an der SFU Berlin e.V.,437638.55,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience",Communication,2020 +P24993,01IS20S31,Software Sprint - individual project: Commissura - Digitalisation of therapist-client interaction in psychotherapy,,,2020,"Capito, Herrmann & Becker GbR",52725,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24994,01IS20S24,Software Sprint - individual project: CoVerified - With CoVerified,,,2020,"Diehl, Fetzer, Hiry, Hochrein, Killian, Mayer, Schlittenbauer, Schweikert, Vollnhals, Weise GbR",52592.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24996,01IS20S27,Software Sprint - Individual project: optimiseTheCurve - Getting started with pandemic simulation,,,2020,"optimizethecurve.eu - Ahlgrimm, Wagner und Waldmüller GbR",19709.16,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P24997,01KI20521A,CancerCOVID - Resource allocation for cancer medicine in the context of Sars-CoV-2 - Subproject Empirical-ethical analyses.,"The outbreak of Sars-CoV-2 triggered unprecedented preparations for the care of patients with COVID-19 (1). In addition, access to hospitals and outpatient clinics was restricted due to specific hygiene regulations. Allocation of health resources in times of pandemic has potential clinical and ethically relevant implications for non-COVID-19 patients (2, 3). However, a systematic assessment of evidence and interdisciplinary analyses regarding ethical and social aspects related to care for non-COVID-19 patients during the pandemic is missing. The interdisciplinary CancerCOVID consortium will analyse possible implications of the outbreak of Sars-CoV-2 for the access, process and outcomes of care, with a focus on patients with cancer in Germany. For this purpose we will analyse quantitative data derived from the registry of colon cancer centres and data from the statutory health insurance on the care of patients with cancer, diabetes and coronary heart disease. In addition we will explore the ethical and psycho-social challenges perceived by patients and health professionals during the pandemic by means of semi-structured interviews. Based on the findings and together with major decision makers in the German healthcare system we will develop guidance for clinical and health policy decisions about priority settings regarding cancer care in times of pandemics and comparable major events.",,2022,Martin-Luther-Universität Halle-Wittenberg,148928.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Health Personnel | Hospital personnel,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2020 +P24998,01KI20521B,CancerCOVID - Resource Allocation for Cancer Medicine in the Context of Sars-CoV-2 - Health Services Research Subproject.,"The outbreak of Sars-CoV-2 triggered unprecedented preparations for the care of patients with COVID-19 (1). In addition, access to hospitals and outpatient clinics was restricted due to specific hygiene regulations. Allocation of health resources in times of pandemic has potential clinical and ethically relevant implications for non-COVID-19 patients (2, 3). However, a systematic assessment of evidence and interdisciplinary analyses regarding ethical and social aspects related to care for non-COVID-19 patients during the pandemic is missing. The interdisciplinary CancerCOVID consortium will analyse possible implications of the outbreak of Sars-CoV-2 for the access, process and outcomes of care, with a focus on patients with cancer in Germany. For this purpose we will analyse quantitative data derived from the registry of colon cancer centres and data from the statutory health insurance on the care of patients with cancer, diabetes and coronary heart disease. In addition we will explore the ethical and psycho-social challenges perceived by patients and health professionals during the pandemic by means of semi-structured interviews. Based on the findings and together with major decision makers in the German healthcare system we will develop guidance for clinical and health policy decisions about priority settings regarding cancer care in times of pandemics and comparable major events.",,2022,Technische Universität Dresden,192637.95,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management | Research to inform ethical issues | Health Systems Research,"Supportive care, processes of care and management | Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in the Allocation of Resources | Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Health service delivery",2020 +P24999,01IS20S12,Software Sprint - individual project: CoResponse - Monitoring by means of Smart Care in isolation,,,2020,"CoResponse - Zimmer, Jünemann, Maier, Mobaiyed, Andree, Röper, Klöpper GbR",52703.91,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Health Systems Research,Health service delivery,2020 +P25000,01IS20S18,Software Sprint - individual project: Digital waiting room,,,2020,WillemGroßeRüschkampWittmann GbR,45396.78,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25001,01KI20239B,ExComPat-Covid19 - Experimental and computational analysis of infection dynamics and lung pathology in COVID-19 - Subproject B,"The infection dynamics of SARS-CoV-2 within the lung and its association with disease progression is still incompletely understood. To which extent viral replication kinetics and virus-associated tissue pathology determine patient outcome remains an open question that is of urgent importance to advise effective treatment strategies. In this project, we will combine experimental data of lung organoids with detailed mathematical and computational models to assess SARS-CoV-2 infection kinetics under physiologically relevant conditions. By integrating spatially-resolved microscopy images with time course infection data of SARS-CoV-2 in lung organoids by mathematical analyses we will be able to quantify key parameters governing viral replication and spread, and their association with pathological changes. Extending the computational model to extrapolate infection dynamics within a human lung, we will be able to relate observed viral load kinetics in SARS-CoV-2 infected patients to expected tissue pathology and disease progression. This will help to assess the significance of viral load levels for associated lung pathology during infection. Our interdisciplinary approach will improve our understanding of SARS-CoV-2 replication and spread within lung tissue and its association with disease progression. Furthermore, the inferred computational model provides a tool to test the efficacy of antiviral therapies and represents a first step towards a mechanistic model of infection progression within tissue that could improve our understanding of individual patient outcome.",,2021,Universität Heidelberg,105602.99,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis,2020 +P25002,01KI20239A,ExComPat-Covid19 - Experimental and computational analysis of infection dynamics and lung pathology in COVID-19 - Subproject A,"The infection dynamics of SARS-CoV-2 within the lung and its association with disease progression is still incompletely understood. To which extent viral replication kinetics and virus-associated tissue pathology determine patient outcome remains an open question that is of urgent importance to advise effective treatment strategies. In this project, we will combine experimental data of lung organoids with detailed mathematical and computational models to assess SARS-CoV-2 infection kinetics under physiologically relevant conditions. By integrating spatially-resolved microscopy images with time course infection data of SARS-CoV-2 in lung organoids by mathematical analyses we will be able to quantify key parameters governing viral replication and spread, and their association with pathological changes. Extending the computational model to extrapolate infection dynamics within a human lung, we will be able to relate observed viral load kinetics in SARS-CoV-2 infected patients to expected tissue pathology and disease progression. This will help to assess the significance of viral load levels for associated lung pathology during infection. Our interdisciplinary approach will improve our understanding of SARS-CoV-2 replication and spread within lung tissue and its association with disease progression. Furthermore, the inferred computational model provides a tool to test the efficacy of antiviral therapies and represents a first step towards a mechanistic model of infection progression within tissue that could improve our understanding of individual patient outcome.",,2022,Universität Heidelberg,109645.17,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis,2020 +P25003,01KI20239C,ExComPat-Covid19 - Experimental and computer-based analysis of infection dynamics and lung pathology in COVID-19 - Subproject C,"The infection dynamics of SARS-CoV-2 within the lung and its association with disease progression is still incompletely understood. To which extent viral replication kinetics and virus-associated tissue pathology determine patient outcome remains an open question that is of urgent importance to advise effective treatment strategies. In this project, we will combine experimental data of lung organoids with detailed mathematical and computational models to assess SARS-CoV-2 infection kinetics under physiologically relevant conditions. By integrating spatially-resolved microscopy images with time course infection data of SARS-CoV-2 in lung organoids by mathematical analyses we will be able to quantify key parameters governing viral replication and spread, and their association with pathological changes. Extending the computational model to extrapolate infection dynamics within a human lung, we will be able to relate observed viral load kinetics in SARS-CoV-2 infected patients to expected tissue pathology and disease progression. This will help to assess the significance of viral load levels for associated lung pathology during infection. Our interdisciplinary approach will improve our understanding of SARS-CoV-2 replication and spread within lung tissue and its association with disease progression. Furthermore, the inferred computational model provides a tool to test the efficacy of antiviral therapies and represents a first step towards a mechanistic model of infection progression within tissue that could improve our understanding of individual patient outcome.",,2021,Deutsches Krebsforschungszentrum (DKFZ),19740,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis,2020 +P25004,01KI20198B,"GI-SARS-2 - Gastrointestinal manifestations of SARS-CoV-2, relevance to viral replication, spread and pathogenesis.","Although there are accumulating evidence that the intestinal epithelium is infected by SARS-CoV-2, the importance of this enteric phase for virus-induced pathologies, spreading and prognosis remain unknown. Here, we will engage in the comprehensive analysis of SARS-CoV-2 life-cycle in the human intestinal epithelium. (1) we will evaluate if there are infectious virus particles in stool. (2) we will develop standardized protocols to establish a robust measure for enteric virus shedding. (3) in organoids models, we will characterize how SARS-CoV-2 infects, replicates and is released from intestinal epithelial cells. This will provide the molecular basis of the enteric lifecycle and will enable us to determine the origin of the enteric phase (fecal/oral transmission vs. spreading from lung to gut). To these goals, we will exploit a pipeline combining single cell sequencing and spatial transcriptomics which we developed to study host-virus interaction. Combined with in-situ measurement of immune response in biopsies, we will define whether exacerbated gut inflammation contributes to the lung pathology observed in patients through cytokine storm-induced cytopathic effects. We anticipate that understanding the enteric phase of SARS-CoV-2 will provide us with critical pieces of evidence to outline novel perspectives to treat the disease and eradicate the virus. Most importantly, quantifying the relevance of fecal transmission and its link to SARS-CoV-2 etiology is urgently needed to implement epidemiological and societal measures aiming at monitoring and controlling the virus.",,2021,Europäisches Laboratorium für Molekularbiologie (EMBL),19706,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P25005,01KI20328A,RENACO - Repurposing of nafamostat mesylate for the treatment of COVID-19 - Subproject A,"The novel, pandemic coronavirus (SARS-CoV-2) and the associated disease COVID-19 threaten public health and economies worldwide. In the light of a constantly rising death toll, drugs are urgently needed. The only way to meet this need is to repurpose drugs that have been approved for treatment of other diseases. We have recently shown that the cellular serine protease TMPRSS2 is essential for SARS-CoV-2 infection of lung cells and that a clinically proven TMPRSS2 inhibitor, camostat mesylate, blocks infection. Our recent results show that the FDA-approved serine protease inhibitor nafamostat mesylate, which is used in Japan for treatment of pancreatitis, has 50-fold higher antiviral activity as compared to camostat mesylate. The goal of the present study is to develop nafamostat mesylate for treatment of SARS-CoV-2 infection. For this, we will pursue three goals: First, as proof-of-concept, we will determine the antiviral activity of nafamostat mesylate in a non-human primate (NHP) model of SARS-CoV-2 infection. For this, the compound will be applied intravenously, the route of application used in pancreatitis patients. Second, we will analyze whether the compound can be nebulized and safely applied to the airways. For this, safety and pharmacokinetic studies of the inhaled drug will be conducted in rats and ex vivo lung tissue. Third, we will determine whether application of nafamostat mesylate to the upper respiratory tract of NHP as spray inhibits SARS-CoV-2 spread and could be used for prevention of COVID-19.",,2022,Deutsches Primatenzentrum Gesellschaft mit beschränkter Haftung - Leibniz-Institut für Primatenforschung,603284.2,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P25006,01KI20328B,RENACO - Repurposing of nafamostat mesylate for the treatment of COVID-19 - Subproject B,"The novel, pandemic coronavirus (SARS-CoV-2) and the associated disease COVID-19 threaten public health and economies worldwide. In the light of a constantly rising death toll, drugs are urgently needed. The only way to meet this need is to repurpose drugs that have been approved for treatment of other diseases. We have recently shown that the cellular serine protease TMPRSS2 is essential for SARS-CoV-2 infection of lung cells and that a clinically proven TMPRSS2 inhibitor, camostat mesylate, blocks infection. Our recent results show that the FDA-approved serine protease inhibitor nafamostat mesylate, which is used in Japan for treatment of pancreatitis, has 50-fold higher antiviral activity as compared to camostat mesylate. The goal of the present study is to develop nafamostat mesylate for treatment of SARS-CoV-2 infection. For this, we will pursue three goals: First, as proof-of-concept, we will determine the antiviral activity of nafamostat mesylate in a non-human primate (NHP) model of SARS-CoV-2 infection. For this, the compound will be applied intravenously, the route of application used in pancreatitis patients. Second, we will analyze whether the compound can be nebulized and safely applied to the airways. For this, safety and pharmacokinetic studies of the inhaled drug will be conducted in rats and ex vivo lung tissue. Third, we will determine whether application of nafamostat mesylate to the upper respiratory tract of NHP as spray inhibits SARS-CoV-2 spread and could be used for prevention of COVID-19.",,2021,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,1264957.47,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P25007,01DU20005C,Collaborative project: Epidemiological surveillance of infectious diseases in Sub-Saharan Africa; Sub-project C,,,2023,Universitätsklinikum Hamburg-Eppendorf (UKE),159824.18,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25008,01DU20005A,Collaborative project: Epidemiological surveillance of infectious diseases in Sub-Saharan Africa; Sub-project A,,,2023,Bernhard-Nocht-Institut für Tropenmedizin (BNITM),367611.23,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Disease surveillance & mapping,2020 +P25010,01KI20377A,ProDiag - In-depth characterization of the plasma and urine proteome of COVID-19 patients for prediction of disease progression - subproject A,"The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread around the world and infects millions of people. The high number of patients with severe COVID-19 response has led to unmanageable situations for healthcare systems, already resulting in thousands of deaths. To this end, we will use well-documented longitudinal COVID-19 cohorts, along with matching non-COVID-19 controls, comprising of plasma and urine samples collected in a highly standardized fashion. Each cohort will consist of a subgroup of patients showing mild symptoms and patients whose condition has deteriorated to a critical status. We will use a standardized sample collection pipeline including laboratory medicine analysis for consecutive sampling of a discovery and a validation cohort. Collection is ongoing with >400 samples per day (sample count: 7685 as of April 21, 2020). The samples will be selected based on clinical data out of our local COVID-19 patient registry CORKUM at LMU Hospital and analyzed using our cutting-edge mass spectrometry (MS)-based proteomics pipeline. The results will mirror the patients' disease state as reflected by concentrations of proteins in blood plasma and urine. We will apply our bioinformatics pipeline to uncover biomarkers and combine them in different risk assessment models (1) to differentiate between COVID-19 and non-COVID-19 patients, (2) to predict the disease trajectory in mild or severe disease courses, and (3) to predict the clinical outcome. This will ultimately allow personalized interventions and guiding the allocation of medical resources.",,2022,Ludwig-Maximilians-Universität München,1202878.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +P25011,01KI20377B,ProDiag - In-depth characterization of the plasma and urine proteome of COVID-19 patients to predict disease progression - subproject B,"The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread around the world and infects millions of people. The high number of patients with severe COVID-19 response has led to unmanageable situations for healthcare systems, already resulting in thousands of deaths. To this end, we will use well-documented longitudinal COVID-19 cohorts, along with matching non-COVID-19 controls, comprising of plasma and urine samples collected in a highly standardized fashion. Each cohort will consist of a subgroup of patients showing mild symptoms and patients whose condition has deteriorated to a critical status. We will use a standardized sample collection pipeline including laboratory medicine analysis for consecutive sampling of a discovery and a validation cohort. Collection is ongoing with >400 samples per day (sample count: 7685 as of April 21, 2020). The samples will be selected based on clinical data out of our local COVID-19 patient registry CORKUM at LMU Hospital and analyzed using our cutting-edge mass spectrometry (MS)-based proteomics pipeline. The results will mirror the patients' disease state as reflected by concentrations of proteins in blood plasma and urine. We will apply our bioinformatics pipeline to uncover biomarkers and combine them in different risk assessment models (1) to differentiate between COVID-19 and non-COVID-19 patients, (2) to predict the disease trajectory in mild or severe disease courses, and (3) to predict the clinical outcome. This will ultimately allow personalized interventions and guiding the allocation of medical resources.",,2022,Exact Sciences Proteomics GmbH,73114.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +P25012,01KI20533A,LwC-Africa - Life with Corona in Africa,"The overall objective of LwC-Africa is to generate new evidence and policy guidelines on how African citizens respond to and cope with the profound global shock to their lives and livelihoods caused by Covid-19. The LwC-Africa project builds on a unique Life in Corona online survey to advance understanding of how the pandemic is affecting health, food, work, gender and social cohesion outcomes to better prepare communities and governments to respond to the challenges ahead as the pandemic spreads across the continent. The LwC-Africa project will collect four quarterly repeated cross-sectional phone-based surveys over 12 months. The final choice of African case study countries will be made during the inception phase of the project. The objectives of the project are: - advance conceptual understanding of how a global pandemic impacts Africa - design research methods to generate rigorous evidence for pandemic - generate phone survey data on how people in five Sub-Saharan African countries are coping with the pandemic - analysis on the impacts of the pandemic - support policy actions to mitigate the effects of the pandemic The project will be implemented by a leading team of social and natural science researchers at two German research institutes and their international partners. The findings of this project will advance our understanding of the special challenges of coping with Corona in low income and fragile settings and will contribute to better policies and aid programmes to support the most vulnerable population groups in the vulnerable countries in Africa.",,2022,Leibniz-Institut für Gemüse- und Zierpflanzenbau (IGZ) e V.,382593.55,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P25013,01KI20533B,LwC-Africa - Life with Corona in Africa,"The overall objective of LwC-Africa is to generate new evidence and policy guidelines on how African citizens respond to and cope with the profound global shock to their lives and livelihoods caused by Covid-19. The LwC-Africa project builds on a unique Life in Corona online survey to advance understanding of how the pandemic is affecting health, food, work, gender and social cohesion outcomes to better prepare communities and governments to respond to the challenges ahead as the pandemic spreads across the continent. The LwC-Africa project will collect four quarterly repeated cross-sectional phone-based surveys over 12 months. The final choice of African case study countries will be made during the inception phase of the project. The objectives of the project are: - advance conceptual understanding of how a global pandemic impacts Africa - design research methods to generate rigorous evidence for pandemic - generate phone survey data on how people in five Sub-Saharan African countries are coping with the pandemic - analysis on the impacts of the pandemic - support policy actions to mitigate the effects of the pandemic The project will be implemented by a leading team of social and natural science researchers at two German research institutes and their international partners. The findings of this project will advance our understanding of the special challenges of coping with Corona in low income and fragile settings and will contribute to better policies and aid programmes to support the most vulnerable population groups in the vulnerable countries in Africa.",,2022,ISDC - International Security and Development Center gGmbH,206208.94,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P25014,01KI20434A,ProteoCoV - Proteostasis as a target for antiviral therapies against SARS-CoV-2 - Influence of SARS-CoV-2 on proteostatic processes of the cell.,"Therapeutic approaches against SARS-CoV-2 currently focus on repurposing of clinically approved drugs. Functional details on how these drugs affect SARS-CoV-2 are often unknown putting patient safety and clinical trials at risk. Our previous study on MERS-CoV revealed that autophagy, a mechanism for non-selective lysosomal protein degradation, is blocked by MERS-CoV infection. We now confirmed that SARS-CoV-2 also limits autophagy. Targeted induction of autophagy by clinically approved drugs reduced MERS-CoV and SARS-CoV-2 replication. Our preliminary data suggest that SARS-CoV-2 promotes selected degradation of proteins by activation of the ubiquitin proteasome system (UPS). We propose that SARS-CoV-2 modulates proteostasis by inhibiting non-selective autophagy while promoting selective proteasomal degradation. In the proposed project, we will perform pulsed-SILAC to analyze details of protein degradation processes upon SARS-CoV-2 infection on a proteome-wide scale. Identification, characterization and validation of candidate proteins and respective protein-targeting drugs will be done by established in silico, molecular and protein-biochemical techniques in combination with virological methods. Identified, clinically approved drugs will be tested by implemented in vitro methods to determine SARS-CoV-2 growth inhibition in non-toxic, nanomolar concentrations possibly encouraging clinical trials. The mechanistic insights into the virus host interplay will reveal novel, hypothesis-driven treatment and drug repurposing strategies against SARS-CoV-2.",,2021,Rheinische Friedrich-Wilhelms-Universität Bonn,282894.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Pre-clinical studies,2020 +P25015,01KI20434B,ProteoCoV - Proteostasis as a target for antiviral therapies against SARS-CoV-2 - Characterization of proteostasis-specific inhibitors against SARS-CoV-2.,"Therapeutic approaches against SARS-CoV-2 currently focus on repurposing of clinically approved drugs. Functional details on how these drugs affect SARS-CoV-2 are often unknown putting patient safety and clinical trials at risk. Our previous study on MERS-CoV revealed that autophagy, a mechanism for non-selective lysosomal protein degradation, is blocked by MERS-CoV infection. We now confirmed that SARS-CoV-2 also limits autophagy. Targeted induction of autophagy by clinically approved drugs reduced MERS-CoV and SARS-CoV-2 replication. Our preliminary data suggest that SARS-CoV-2 promotes selected degradation of proteins by activation of the ubiquitin proteasome system (UPS). We propose that SARS-CoV-2 modulates proteostasis by inhibiting non-selective autophagy while promoting selective proteasomal degradation. In the proposed project, we will perform pulsed-SILAC to analyze details of protein degradation processes upon SARS-CoV-2 infection on a proteome-wide scale. Identification, characterization and validation of candidate proteins and respective protein-targeting drugs will be done by established in silico, molecular and protein-biochemical techniques in combination with virological methods. Identified, clinically approved drugs will be tested by implemented in vitro methods to determine SARS-CoV-2 growth inhibition in non-toxic, nanomolar concentrations possibly encouraging clinical trials. The mechanistic insights into the virus host interplay will reveal novel, hypothesis-driven treatment and drug repurposing strategies against SARS-CoV-2.",,2021,Charité - Universitätsmedizin Berlin,295054.06,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P25016,01DU20005B,Collaborative project: Epidemiological surveillance of infectious diseases in Sub-Saharan Africa; Sub-project: Development of cross-disciplinary data infrastructures and competence networking in epidemiological surveillance of infectious diseases in sub-Saharan Africa,,,2023,Hochschule für Angewandte Wissenschaften Hamburg,478328.3,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25017,01KI20700,BNT-Covid-19 vaccine - Accelerated development and delivery of an mRNA-based COVID-19 vaccine (BNT162).,"In BIO-PROTECT we investigate filtration efficacy, pressure characteristics and effects on the load of breathing for different kinds of face masks in high- and low-risk populations and in relation to wearing time.",,2021,BioNTech SE,416252543,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P25018,01DK20101A,"Collaborative project: Inclusive and integrated multi-hazard risk management, volunteer engagement to increase social resilience in climate change (INCREASE); sub-project: Integrated disaster risk management, increasing the resilience of the population in Iran and Germany in times of Covid-19, climate change",,,2025,Freie Universität Berlin,2008194.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Other secondary impacts,2021 +P25019,01KI20700I,BNT-Covid-19-Vaccine-I - Investments for the accelerated development and delivery of an mRNA-based COVID-19 vaccine (BNT162),,,2021,BioNTech SE,0,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Vaccines research, development and implementation",,2020 +P25020,03COV13A,"CORONA - TOPAS-COVID19 - Wear-physiologically optimised protective masks suitable for everyday use; TP1: Modelling of a wear-physiologically optimised, combinable mask construction",,,2022,Sächsisches Textilforschungsinstitut e.V.,232849.01,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P25021,03COV23B,CORONA - BEAD-Dx -Bead-based Multiplex-Assay; Subproject B,,,2022,PolyAn Gesellschaft zur Herstellung von Polymeren für spezielle Anwendungen und Analytik mbH,87012.66,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25022,03COV23A,CORONA - BEAD-Dx - Bead-basierter Multiplex-Assay - Subproject A,,,2022,Medipan GmbH,206210.98,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25023,03COV15B,CORONA - CONTENT - Collaborative project: Development of structures for infection prevention checkpoints at building entrances; TV2: CONTAIN,,,2023,Charité - Universitätsmedizin Berlin,464372.92,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25024,01DS20006,Project 'Impact': Establishment of a German-Italian think tank to analyse the consequences of the COVID-19 pandemic,,,2023,Villa Vigoni e.V.,643008.89,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",,2020 +P25027,02WRS1557B,"RiSKWa - Collaborative Project Wastewater Biomarker CoV2: Wastewater epidemiology using the example of a SARS-CoV-2 biomarker for estimating COVID-19 infections at the population scale, Subproject 2.","The aim of the funding measure ""Risk Management of New Pollutants and Pathogens in the Water Cycle (RiSKWa)"" was to develop an innovative and dynamic system of risk management for preventive health and environmental protection and to implement it in the form of individual examples. The funding measure RiSKWa with its 12 collaborative projects and the accompanying scientific project was intended to contribute to the identification of risks, the development of technologies and strategies for their avoidance or reduction, and the development of educational and communication measures for the establishment of effective risk management and preventive environmental and health protection.",,2023,DVGW Deutscher Verein des Gas- und Wasserfaches e.V. - Technisch-wissenschaftlicher Verein,1008280.26,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Communication,2020 +P25028,02WRS1557A,"RiSKWa - Collaborative project wastewater biomarker CoV2: wastewater epidemiology using the example of a SARS-CoV-2 biomarker for estimating COVID-19 infections at the population scale, subproject 1.","The aim of the funding measure ""Risk Management of New Pollutants and Pathogens in the Water Cycle (RiSKWa)"" was to develop an innovative and dynamic system of risk management for preventive health and environmental protection and to implement it in the form of individual examples. The funding measure RiSKWa with its 12 collaborative projects and the accompanying scientific project was intended to contribute to the identification of risks, the development of technologies and strategies for their avoidance or reduction, and the development of educational and communication measures for the establishment of effective risk management and preventive environmental and health protection.",,2023,Technische Universität München,1694312.1,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Communication,2020 +P25029,02WRS1557C,"RiSKWa - Collaborative project wastewater biomarker CoV2: wastewater epidemiology using the example of a SARS-CoV-2 biomarker for estimating COVID-19 infections at the population scale, subproject 1.","The aim of the funding measure ""Risk Management of New Pollutants and Pathogens in the Water Cycle (RiSKWa)"" was to develop an innovative and dynamic system of risk management for preventive health and environmental protection and to implement it in the form of individual examples. The funding measure RiSKWa with its 12 collaborative projects and the accompanying scientific project was intended to contribute to the identification of risks, the development of technologies and strategies for their avoidance or reduction, and the development of educational and communication measures for the establishment of effective risk management and preventive environmental and health protection.",,2023,Blue Biolabs GmbH,57069.09,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Communication,2020 +P25030,13N15603,Collaborative project: Real-world laboratories for distributed information and training of the civilian population in crisis situations (REALIS) - sub-project: University of Siegen,,,2022,Universität Siegen,143857.84,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25031,13N15602,Collaborative project: Real-world laboratories for distributed information and training of the civilian population in crisis situations (REALIS) - sub-project: City of Siegen,,,2022,Stadt Siegen,128087.8,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25032,16KIS1280,"Collaborative project: Automated resilience and secure networks for critical infrastructures and companies - AI-NET-PROTECT -; sub-project: Automation, security and performance monitoring of data centre networks",,,2024,"Gesellschaft für wissenschaftliche Datenverarbeitung mbH, Göttingen",946083.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,Health information systems,2021 +P25033,03COV26B,CORONA - DIGIVID19 - Collaborative project: Development of a digital therapy approach to support post-inpatient rehabilitation of the respiratory tract after surviving Covid19 infection- Subproject,,,2021,2tainment GmbH,143345.7,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25034,13N15662,Modelling and simulation of Covid infection spread in crowds in system-relevant infrastructures (CovidSim),,,2021,Hochschule für angewandte Wissenschaften München,491589.18,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Disease transmission dynamics,2021 +P25035,16KIS1292,Collaborative project: Automated resilience and secure networks for critical infrastructures and companies - AI-NET-PROTECT -; sub-project: Predictive Covid-19 connector based on artificial intelligence,,,2024,Georg-August-Universität Göttingen - Universitätsmedizin,328242.82,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,Health information systems,2021 +P25036,01KA2029,Intensify and continue TB Sequel activities and outcomes in the Covid 19 pandemic period (EnhanceTBSequel).,"In general, the activities planned in this project primarily serve to achieve the scientific as well as technical (e.g. training of scientific staff in Africa and development of scientific infrastructure) objectives of the TB Sequel study. A major focus of this proposal is the integration and funding of measures and data collection to address the new epidemiological situation caused by the Covid-19 pandemic. Furthermore, the TB Sequel Network researchers and research teams see the additional funding as a unique opportunity to be able to investigate relevant scientific questions on covid-19 in a huge African cohort, including the interaction of covid-19 and TB, but also to support promising pilot studies on post-TB lung disease (PTLD) and new ideas of young researchers developed during the implementation of the study and in the context of newly developed research collaborations between the participating research partners in recent years. Thus, with this request for additional funding, the TB Sequel Network also aims to lay the groundwork for future research proposals that build on the data and findings from TB Sequel (and the accompanying Covid 19 research) and that aim to develop new strategies and/or therapeutic interventions for the prevention, treatment and supportive care of PTLD.",,2022,Ludwig-Maximilians-Universität München,907866.65,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation",Disease transmission dynamics | Disease pathogenesis | Prophylactic use of treatments,2021 +P25037,01KA2022,"Development, synthesis and translation of evidence in the COVID-19 pandemic",,,2022,Albert-Ludwigs-Universität Freiburg,101591.16,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25038,01KA2023,"Development, synthesis and translation of evidence in the COVID-19 pandemic",,,2022,Ludwig-Maximilians-Universität München,856753.81,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25039,16KIS1298,Collaborative project: Automated resilience and secure networks for critical infrastructures and companies - AI-NET-PROTECT -; sub-project: Health Data Intelligence: Security and Data Protection (AI-NET-PROTECT 4 health),,,2024,Universität Koblenz,986645.62,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,Health information systems,2021 +P25040,03COV26C,"CORONA - DIGIVID19 - Collaborative project: Development of a digital therapy approach to support post-inpatient rehabilitation of the respiratory tract after surviving Covid19 infection, Subproject C",,,2023,LichterSchatten - Therapiezentrum GmbH,254319.19,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25041,13N15663,Cockpit for regional pandemic management with agent-based social simulation (AScore),,,2021,Deutsches Forschungszentrum für Künstliche Intelligenz GmbH,691341.86,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Disease surveillance & mapping,2021 +P25042,03COV26A,CORONA - DIGIVID19 - Collaborative project: Development of a digital therapy approach to support post-inpatient rehabilitation of the respiratory tract after surviving Covid19 infection- Subproject A,,,2023,Martin-Luther-Universität Halle-Wittenberg,612497.82,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25043,02WRS1559,RiSKWa - CoroMoni project: Development of a communication platform on the topic of wastewater monitoring to determine the SARS-CoV-2 infection level of the population for networking research actors in Germany,,,2023,"Deutsche Vereinigung für Wasserwirtschaft, Abwasser und Abfall e.V. (DWA)",412464,Human Populations | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Communication,2020 +P25044,03COV21D,"CORONA - EPI-Dx - Epidemiological study on peptide signatures, immunity, genetic predisposition and changes in SARS-CoV-2;",,,2023,MicroDiscovery GmbH,258592.05,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease surveillance & mapping | Prognostic factors for disease severity",2021 +P25045,01QE2106,Verbundprojekt: Eine kostengünstige und breit anwendbare Mimetop-basierte Diagnoseplattform für hoch bedrohliche Pandemien; Teilprojekt: Entwicklung und Leistungsbewertung von magnetischen Schnellteststreifen für COVID-20 Collaborative project: A cost-effective and widely applicable mimetope-based diagnostic platform for highly threatening pandemics; Subproject: Development and performance evaluation of rapid magnetic test strips for COVID-20,,,2024,Lionex GmbH,360495.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25046,01DG21014,Verbundprojekt: Einsatz mobiler Technologien zur Prävention von COVID-19-Infektionen bei vulnerablen Müttern im ländlichen Südwesten Ugandas Collaborative project: Use of mobile technologies to prevent COVID-19 infections among vulnerable mothers in rural southwest Uganda,,,2022,Humboldt-Universität zu Berlin,188871.95,Human Populations,Black,Adults (18 and older),Rural Population/Setting,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +P25047,01QE2121,"Collaborative project: Risk of viral infections in buildings through airborne transmission of pathogens; Subproject: Behavior of aerosols within air distribution systems in rooms or buildings"" (using google translate)""",,,2024,GenXPro GmbH,298432.25,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25048,01QC2101C,Verbundprojekt: Risiko von Virusansteckungen in Gebäuden durch Übertragung von Krankheitserregern über die Luft; Teilprojekt: Verhalten von Aerosolen innerhalb von Luftverteilungssystemen in Räumen bzw. Gebäuden Collaborative project: Risk of viral infections in buildings through airborne transmission of pathogens; Subproject: Behavior of aerosols within air distribution systems in rooms or buildings,,,2024,Technische Universität Dresden,343570.1,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25049,02WRS1602A,"RiSKWa - Joint project SARS-GenASeq: The SARS-CoV-2 genome in wastewater, Subproject A",,,2023,Technische Universität Darmstadt,1854634.86,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease surveillance & mapping,2021 +P25050,02WRS1602B,"RiSKWa - Joint project SARS-GenASeq: The SARS-CoV-2 genome in wastewater, Subproject B",,,2023,Emschergenossenschaft,70828.34,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease surveillance & mapping,2021 +P25051,13N15745,"Collaborative project: Early and rapid methods of diagnosis and therapy of viral infections (SARSCoV2Dx)) - Teilvorhaben: COVID-19: Diagnostik, Therapiestrategien & Management",,,2026,Universitätsklinikum Jena,8268480,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P25052,13GW0540B,Collaborative project: Point-of-care platform for the differential diagnosis of viral and bacterial respiratory tract infections (COVIRES) - Subproject B,,,2023,Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.,245644.56,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P25053,13GW0540C,Collaborative project: Point-of-care platform for the differential diagnosis of viral and bacterial respiratory tract infections (COVIRES) - Subproject C,,,2023,Albert-Ludwigs-Universität Freiburg,190638,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P25054,16LW0001,COVID-19 Therapeutics I: Clinical Evidence Studies for the Efficacy and Safety of ATR-002 in Patients with COVID-19 (MEK-I-COV),,,2023,ATRIVA Therapeutics GmbH,13915182.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25055,16LW0002K,COVID-19 Therapeutics I: Restoration of endothelial barrier function by adrecizumab for the treatment of life-threatening organ failure (RESCUE) - Initiation and overall coordination,,,2023,AdrenoMed AG,485197.9,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2021 +P25056,16LW0004K,COVID-19 therapeutics I: Drug combination for the therapeutic induction of T cells against COVID-19 (IndTCOVID-19) - compounds for clinical trials and peptides for immune monitoring,,,2023,EMC microcollections GmbH,415465.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2021 +P25057,16LW0005,COVID-19 therapeutics I: Drug combination for the therapeutic induction of T cells against COVID-19 (IndTCOVID-19) - clinical trial and immunomonitoring,,,2023,Eberhard Karls Universität Tübingen,1238847.36,Human Populations,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2021 +P25058,16LW0006,"COVID-19 therapeutics I: Initial clinical application studies, up-scaling and production of GMP material of the complement C5a inhibitor AON-D21 for proof-of-concept in COVID-19 patients (Accelerate-D21)",,,2023,Aptarion Biotech AG,6216270.65,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25059,16LW0007K,COVID-19: CCR1 antagonist for the treatment of hospitalised COVID-19 patients (CATCOVID) - synthesis and upscaling,,,2023,Bayer Aktiengesellschaft,984178.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25060,16LW0008,COVID-19: CCR1 antagonist for the treatment of hospitalised COVID-19 patients (CATCOVID) - study coordination,,,2023,Charité - Universitätsmedizin Berlin,2737449.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25061,16LW0009,COVID-19: CCR1 antagonist for the treatment of hospitalised COVID-19 patients (CATCOVID),,,2023,Universität Leipzig,247888.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25062,16LW0010,COVID-19: CCR1 antagonist for the treatment of hospitalised COVID-19 patients (CATCOVID),,,2023,Universitätsklinikum Würzburg,202251.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25063,16LW0011,COVID-19: CCR1 antagonist for the treatment of hospitalised COVID-19 patients (CATCOVID)) - clinical studies and analysis,,,2023,BG Klinikum Unfallkrankenhaus Berlin gGmbH,201567.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25064,16LW0003,COVID-19 Therapeutics I: Restoration of endothelial barrier function by adrecizumab for the treatment of life-threatening organ failure (RESCUE) - AGNES-19 study,,,2023,Universitätsklinikum Hamburg-Eppendorf,4957188.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2021 +P25065,16LW0012,COVID-19 therapeutics I: Clinical development of our targeted SARS-CoV-2 helicase inhibitor EIS-10700 - inhibition of viral replication for COVID-19 therapy (EisCor_2).,,,2023,Eisbach Bio GmbH,9754346.03,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25066,16LW0013K,COVID-19 therapeutics I: Studies on the inhalation use of MAS receptor agonists in acute lung injury caused by COVID-19 (STAMINA) - GMP production of test substance,,,2023,Explicat Pharma GmbH,448960,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2021 +P25067,16LW0014,COVID-19 therapeutics I: Studies on the inhalation use of MAS receptor agonists in acute lung injury caused by COVID-19 (STAMINA) - synthesis process,,,2023,ABX advanced biochemical compounds - Biomedizinische Forschungsreagenzien GmbH,430205.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",Therapeutics logistics and supply chains and distribution strategies,2021 +P25068,16LW0015,COVID-19 therapeutics I: Studies on the inhalation use of MAS receptor agonists in acute lung injury caused by COVID-19 (STAMINA) - Clinical studies,,,2023,Universitätsklinikum Ulm,3348123.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase)",2021 +P25069,16LW0016,COVID-19 Therapeutics I: Efficacy of COR-101 for the treatment of hospitalised patients with moderate to severe COVID-19 disease (CORAT-1),,,2023,CORAT Therapeutics GmbH,8966211.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25070,13GW0540A,Collaborative project: Point-of-care platform for the differential diagnosis of viral and bacterial respiratory tract infections (COVIRES) - Subproject A,,,2023,SpinDiag GmbH,358071,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P25072,13K22GUB,Collaborative project: X-ray-based drug development platform (XDD) - Teilvorhaben: Universität Hamburg,,,2026,Universität Hamburg,256463.28,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified | Not applicable,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2022 +P25073,13GW0546B,Collaborative project: Research into a membrane for the extracorporeal removal of cytokines in the blood (Z-membrane),,,2024,Universitätsklinikum Würzburg,426102.72,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25074,13GW0541C,Collaborative project: Exosome analysis for the clinical diagnosis of SARS-CoV-2-infected organs (VIR-COV)- Subproject C,,,2022,Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH),123799.25,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25075,13GW0541B,Collaborative project: Exosome analysis for the clinical diagnosis of SARS-CoV-2-infected organs (VIR-COV)- Subproject B,,,2022,Klinikum rechts der Isar der Technischen Universität München,119283.84,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25076,01DH21022C,"Collaborative project: ""Molecular point-of-care microfluidic system for rapid diagnostics of viral infections"" - Subproject C",,,2024,nal von minden GmbH,45095.91,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25079,01KA2114A,"TB Sequel - Study of the clinical, microbiological and immunological factors leading to unfavorable pulmonary ""outcome"" in TB patients.","In general, the activities planned in this project serve to consolidate the achieved scientific and technical goals of the TB Sequel study and the TB Sequel network, as well as to further develop them in preparation for the planned application for a second funding period from 2023-2027. Another focus of this application is the integration and funding of measures that address the new epidemiological situation caused by the Covid 19 pandemic. In order to achieve the objectives of the project, the main focus of activities will be on the maintenance of the TB Sequel Cohort. This will be done by continuing the follow-up in 2022 with at least one physical study visit and one additional phone call. At both visits, the most relevant morbidity and mortality data and soc-econ. data with respect to the outcomes studied in TB Sequel to date will be collected. Data will be collected (and clinical samples taken) and either analysed in conjunction with TB Sequel data (2017-2021) or processed and published as part of a stand-alone analysis. In addition to the continuation of the cohort, the coordinators or various investigators of Research Tasks 1-5 will also conduct new studies and investigations that have a completely new aspect to the research subject (e.g. interaction between TB and Covid-19), but are relevant to specific questions in the new funding period, or serve to directly prepare the further funding period (e.g. review and interviews on local infrastructures regarding the future treatment and therapy of patients with post-TB lung disease).",,2023,Ludwig-Maximilians-Universität München,446350,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Unspecified,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,,2021 +P25080,01KA2111B,"Sustainability of the Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) for evidence-based health research and care in sub-Saharan Africa, Subproject B",,,2023,Albert-Ludwigs-Universität Freiburg,284724.86,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25081,01KA2114B,"TB Sequel - Study of the clinical, microbiological and immunological factors leading to unfavorable pulmonary ""outcome"" in TB patients.","In general, the activities planned in this project serve to consolidate the achieved scientific and technical goals of the TB Sequel study and the TB Sequel network, as well as to further develop them in preparation for the planned application for a second funding period from 2023-2027. Another focus of this application is the integration and funding of measures that address the new epidemiological situation caused by the Covid 19 pandemic. This involves ensuring the continuous collection and analysis of TB outcome data (despite the pandemic) as well as the collection of additional Sars-Cov2 relevant data, which are essential for the analysis of the TB Sequel studies (such as Sars-Cov2 prevalence data or sero-status of all participants) or provide new important insights into a possible interaction of both infections TB and Covid-19, which is also relevant for the future scientific direction of the network. At the FZB, studies are being conducted on new clinical samples from TB-Sequel participants to clarify the question of relapse or reinfection. Furthermore, biomarkers are being sought that can provide information about inflammatory processes in the lungs of TB patients with an existing SARS-CoV 2 infection.",,2023,Forschungszentrum Borstel Leibniz Lungenzentrum,203400,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Unspecified,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,,2021 +P25082,02WAP1618,AquaPol - Cooperation project SARA: Surveillance of emerging pathogens and antibiotic resistance in aquatic ecosystems,,,2024,DVGW Deutscher Verein des Gas- und Wasserfaches e.V. - Technisch-wissenschaftlicher Verein,554556.34,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Epidemiological studies,,2021 +P25083,13N15900,"Collaborative project: Optimisation of risk and crisis communication by governments, authorities and health security organisations (MIRKKOMM) - Teilvorhaben: Analyse multimodaler Diskurse in der Risiko- und Krisenkommunikation",,,2024,Bundesinstitut für Risikobewertung (BfR),524633.2,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience",Communication,2021 +P25084,01KA2110A,"ANDEMIA - African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Diseases 2022: Individual capacity building",,,2022,Robert Koch-Institut (RKI),95711.05,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics,2022 +P25085,16LW0108,COVID19AM: Clinical study (COVIC-19) - Effectiveness of early transfusion of convalescent plasma with very high antibody concentrations in vulnerable patients with COVID-19 as a model for early therapy options in pandemic situations caused by new pathogens,,,2023,Deutsches Rotes Kreuz Blutspendedienst Baden-Württemberg - Hessen gemeinnützige Gesellschaft mit beschränkter Haftung,2971655.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +P25086,13GW0541A,Collaborative project: Exosome analysis for the clinical diagnosis of SARS-CoV-2-infected organs (VIR-COV)- Subproject A,,,2022,Therawis Diagnostics GmbH,226546.49,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25087,13GW0596A,"Collaborative project: AI-based lung ultrasound image processing in pneumonia and COVID-19 patients (LUSCOV), Subproject A",,,2024,MedCom Gesellschaft für medizinische Bildverarbeitung mbH,350028,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25088,13GW0596B,"Collaborative project: AI-based lung ultrasound image processing in pneumonia and COVID-19 patients (LUSCOV), Subproject B",,,2024,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,276979.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25089,01DP21011,Collaborative project: Pulmonary blood-air interface model for the investigation of Covid-19 and the screening of therapeutics,,,2024,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,173987.18,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2021 +P25090,16LW0112,COVID19AM: Trimodulin - treatment of severe COVID-19 diseases in a Phase III clinical trial and accelerated upscaling of production (TRICOVID),,,2023,Biotest Aktiengesellschaft,25430188.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Phase 3 clinical trial,2021 +P25091,16LW0113,COVID19AM: Clinical development and production of vilobelimab as a first-in-class anti-C5 antibody for the treatment of critically ill COVID-19 patients (VILO-COVID),,,2023,InflaRx GmbH,38573185.94,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2021 +P25092,16LW0102,COVID19AM: Conducting the Phase III ASUCOV clinical trial to investigate the CD95L inhibitor asunercept in hospitalised COVID-19 patients (ASUCOV),,,2023,Apogenix GmbH,20125486,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Phase 3 clinical trial,2021 +P25093,16LW0107,COVID19AM: Development and Phase II clinical trial to demonstrate the efficacy of the neutralising antibody COR-101 for the treatment of hospitalised patients with moderate to severe COVID-19 disease (CORAMAR),,,2022,CORAT Therapeutics GmbH,6339200.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Phase 2 clinical trial,2022 +P25094,16LW0101,COVID19AM: Drug development to protect vascular function in severe COVID-19 diseases (ACCESS),,,2023,AdrenoMed AG,2622504,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25095,01DP21014,Collaborative project: characterization of T cell immunity against SARS-CoV-2 in Southeast Asian and European populations Subproject: Peptide production,,,2024,Eberhard Karls Universität Tübingen,169014.55,Human Populations,Asian | White,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P25096,031L0292D,CompLS - Round 4 - Collaborative project: GENImmune - Generic methods for modelling host-pathogen interactions applied to efficient immunisation against SARS-CoV-2 - Subproject D,,,2024,Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH),214653.9,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,Severe Acute Respiratory Syndrome (SARS),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P25100,13GW0596C,"Collaborative project: AI-based lung ultrasound image processing in pneumonia and COVID-19 patients (LUSCOV), Subproject C",,,2024,SRH Wald-Klinikum Gera GmbH,118776,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25101,031L0292C,CompLS - Round 4 - Collaborative project: GENImmune - Generic methods for modelling host-pathogen interactions applied to efficient immunisation against SARS-CoV-2 - Subproject C,,,2023,PMCR GmbH,136492.54,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P25102,01UP2100,Survey data as a basis for social science research and policy advice during the Covid-19 pandemic,,,2025,GESIS - Leibniz-Institut für Sozialwissenschaften e.V.,552166.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P25103,01EP2101C,LongCOCid - Long COVID-19 in children - Subproject C,,,2023,Otto-von-Guericke-Universität Magdeburg,40680,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25104,01EP2109A,"PreVitaCOV - Prednisolone and vitamins B1, 6 and 12 in patients with post-COVID-19 syndrome (PC19S) - a randomised controlled pilot study in primary care - Subproject A",,,2024,Universitätsklinikum Würzburg,502656.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25105,01EP2109B,"PreVitaCOV - Prednisolone and vitamins B1, 6 and 12 in patients with post-COVID-19 syndrome (PC19S) - a randomised controlled pilot study in primary care - Subproject B",,,2024,Eberhard Karls Universität Tübingen,270504.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25106,01EP2109C,"PreVitaCOV - Prednisolone and vitamins B1, 6 and 12 in patients with post-COVID-19 syndrome (PC19S) - a randomised controlled pilot study in primary care - Subproject C",,,2024,Christian-Albrechts-Universität zu Kiel,251332.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25107,01EP2110B,LoCoVICF - Restriction of participation and quality of life as well as care needs of those affected in the healthcare system with late symptoms after a SARS-Cov-2 infection: Perspektive Rehabilitationsmedizin,,,2024,Universitätsmedizin Greifswald,164747.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience",Community engagement,2022 +P25108,01EP2101A,LongCOCid - Long COVID-19 in children - Subproject A,,,2023,Universitätsklinikum Jena,216344.1,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25109,01EP2101B,LongCOCid - Long COVID-19 in children - Subproject B,,,2022,Technische Universität Ilmenau,24824.29,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25110,01EP2102A,PulmVasC - Pulmonary vascular dysfunction as a therapeutic starting point for persistent exertional dyspnoea after Covid-19- Subproject A,,,2023,Justus-Liebig-Universität Gießen,480886.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25111,01EP2102B,PulmVasC - Pulmonary vascular dysfunction as a therapeutic starting point for persistent exertional dyspnoea after Covid-19- Subproject B,,,2023,Charité - Universitätsmedizin Berlin,182873.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25112,01EP2102C,PulmVasC - Pulmonary vascular dysfunction as a therapeutic starting point for persistent exertional dyspnoea after Covid-19- Subproject C,,,2023,Medizinische Hochschule Hannover (MHH),82996.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25113,01EP2102D,PulmVasC - Pulmonary vascular dysfunction as a therapeutic starting point for persistent exertional dyspnoea after Covid-19- Subproject D,,,2023,Ludwig-Maximilians-Universität München,104410.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25114,01EP2105A,"COVIDYS - Post-COVID-associated immune dysfunction, Subproject A",,,2023,Universität Regensburg,468693.59,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25115,01EP2105B,"COVIDYS - Post-COVID-associated immune dysfunction, Subproject",,,2023,Universität des Saarlandes,249238.04,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25116,01EP2105C,"COVIDYS - Post-COVID-associated immune dysfunction, Subproject C",,,2023,Technische Universität Dresden,68101.26,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25117,031L0292F,CompLS - Round 4 - Collaborative project: GENImmune - Generic methods for modelling host-pathogen interactions applied to efficient immunisation against SARS-CoV-2 - Subproject F,,,2023,Rheinische Friedrich-Wilhelms-Universität Bonn,223128.06,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P25118,16LW0152K,COVID-19 therapeutics II: Inhaled antimiR against inflammatory lung damage caused by COVID-19 (CoVmiR) - preclinical studies,,,2024,rnatics GmbH,4162010.1,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +P25119,031L0286A,CompLS - Round 4 - Collaborative project: CAP-TSD - Causal analysis and predictive modelling of molecular and clinical time series data of pneumonia patients - Subproject A,,,2025,Universität Leipzig,455790.09,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity,2022 +P25120,031L0286B,CompLS - Round 4 - Collaborative project: CAP-TSD - Causal analysis and predictive modelling of molecular and clinical time series data of pneumonia patients - Subproject B,,,2025,Charité - Universitätsmedizin Berlin,519534.52,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity,2022 +P25121,16LW0153,COVID-19 therapeutics II: Inhaled antimiR against inflammatory lung damage caused by COVID-19 (CoVmiR) - clinical trial,,,2024,LungenClinic Grosshansdorf GmbH,3576252.07,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +P25122,16LW0151,COVID-19 Therapeutics II: Demonstrating the efficacy and safety of tiprelestat for the treatment of COVID-19 (COMCOVID Study),,,2024,tiakis Biotech AG,11214955.23,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25123,16LW0154,COVID 19 II: Treatment of COVID-19 diseases with a novel immunomodulatory molecule (COVIFERON),,,2023,Evotec International GmbH,7354815.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Innovation,,,Germany,,"Therapeutics research, development and implementation",,2021 +P25124,16SV8906,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,Universität Osnabrück,376777.74,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25125,16SV8911,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,Ärztekammer Westfalen-Lippe,105905.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25126,16SV8910,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,accensors GmbH,521399.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25127,16SV8907,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,Deutsches Forschungszentrum für Künstliche Intelligenz GmbH,393382.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25128,16SV8908,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,Strategion GmbH,525719.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25129,16SV8909,KardioInterakt: Multimodal interaction technologies for patient care in care-intensive and COVID-19-related heart diseases in the home environment,,,2025,Universität Münster,150837.19,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25130,13GW0593E,"Collaborative project: On-site monitoring and therapy control of infections using circulating free DNA (EPI-CARE), Subproject E",,,2025,Universitätsmedizin der Johannes Gutenberg-Universität Mainz,167328,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",,2022 +P25131,13GW0592D,Collaborative project: Detection of multiple parameters of the immune response in viral diseases (VirusDual) - Subproject D,,,2023,Eberhard Karls Universität Tübingen,319599.48,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25132,01KA2202A,PROTECT - Protecting foreign health workers: Closing a Gap in Germany's Pandemic Plan and Global Health Policy - Subproject B,,,2023,Medizinische Hochschule Hannover (MHH),76801.23,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25133,01KA2202B,PROTECT - Protecting foreign health workers: Closing a Gap in Germany's Pandemic Plan and Global Health Policy - Subproject B,,,2023,Georg-August-Universität Göttingen,49169.83,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25134,13GW0592E,Collaborative project: Detection of multiple parameters of the immune response in viral diseases (VirusDual) - Subproject E,,,2023,Universität zu Lübeck,320076.72,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25135,13GW0592A,"Collaborative project: Recognition, monitoring and prognosis of multiple COVID-19 long-term consequences (post-COVID syndrome) (Remolco) - Subproject A",,,2023,Bruker BioSpin GmbH & Co. KG,528409.44,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25136,13GW0595A,Collaborative project: Detection of multiple parameters of the immune response in viral diseases (VirusDual) - Subproject A,,,2026,SpinDiag GmbH,381797.4,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P25137,031L0296D,"Modelling network: PROGNOSIS - Epidemic-related resource requirements of hospitals - modelling of incidence, bed occupancy, personnel planning and supply chains - Subproject D",,,2025,Universität Münster,280913.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,,2022 +P25138,031L0296B,"Modelling network: PROGNOSIS - Epidemic-related resource requirements of hospitals - modelling of incidence, bed occupancy, personnel planning and supply chains - Subproject B",,,2025,Universitätsklinikum Aachen,306672.66,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,,2022 +P25139,13GW0595D,Collaborative project: Detection of multiple parameters of the immune response in viral diseases (VirusDual) - Subproject D,,,2026,Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.,356636.35,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P25142,031L0296A,"Modelling network: PROGNOSIS - Epidemic-related resource requirements of hospitals - modelling of incidence, bed occupancy, personnel planning and supply chains - Subproject A",,,2025,Universität Leipzig,423710.99,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,,2022 +P25144,031L0298B,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject B,,,2025,NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen,312610.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25145,031L0296C,"Modelling network: PROGNOSIS - Epidemic-related resource requirements of hospitals - modelling of incidence, bed occupancy, personnel planning and supply chains - Subproject C",,,2025,Technische Universität Dresden,287290.08,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Novel Pathogen,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,Health service delivery,2022 +P25146,031L0296E,"Modelling network: PROGNOSIS - Epidemic-related resource requirements of hospitals - modelling of incidence, bed occupancy, personnel planning and supply chains - Subproject E",,,2025,Universität Augsburg,273509.19,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Health Systems Research,,2022 +P25147,031L0298H,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject H,,,2025,Rheinland-Pfälzische Technische Universität Kaiserslautern-Landau,62348.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25148,031L0298C,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject C,,,2025,Universität Heidelberg,148520.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25149,031L0299I,Modeling network: OptimAgent - Optimized strategies for controlling epidemics in highly heterogeneous populations - Subproject I,,,2025,Universität Bielefeld,95895.28,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2022 +P25151,031L0298G,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject G,,,2025,Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.,310943.21,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25154,01UP2222B,Collaborative project: COMO study: Effects of the COVID-19 pandemic on the physical and mental health and health behaviour of children and adolescents against the background of socio-ecological contexts in Germany. Subproject B,,,2026,Pädagogische Hochschule Karlsruhe,326919.74,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P25155,01UP2222D,Collaborative project: COMO study: Effects of the COVID-19 pandemic on the physical and mental health and health behaviour of children and adolescents against the background of socio-ecological contexts in Germany. Subproject D,,,2026,Universität Konstanz,158946.47,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P25156,01UP2222E,Collaborative project: COMO study: Effects of the COVID-19 pandemic on the physical and mental health and health behaviour of children and adolescents against the background of socio-ecological contexts in Germany. Subproject E,,,2025,Ruhr-Universität Bochum,87784.43,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25157,01QE2207,Collaborative project: A first broad-spectrum antiviral treatment against various corona viruses combined with diagnostics for patient stratification; Teilprojekt: Patientenstratifikation für eine antivirale Behandlung von Corona-Viren,,,2025,Sciomics GmbH,373722.32,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Diagnostics | Prognostic factors for disease severity,2022 +P25158,01UP2222A,Collaborative project: COMO study: Effects of the COVID-19 pandemic on the physical and mental health and health behaviour of children and adolescents against the background of socio-ecological contexts in Germany. Subproject A,,,2026,Karlsruher Institut für Technologie (Universitätsaufgabe),746798.94,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P25159,01UP2222C,Collaborative project: COMO study: Effects of the COVID-19 pandemic on the physical and mental health and health behaviour of children and adolescents against the background of socio-ecological contexts in Germany. Subproject C,,,2026,Universitätsklinikum Hamburg-Eppendorf (UKE),440355.29,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P25160,01UP2201,LoneCOVID: Development and significance of social relationships in the context of the Covid-19 pandemic,,,2026,GESIS - Leibniz-Institut für Sozialwissenschaften e.V.,225456.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P25161,16LW0196,GBi3S: Identification of physical properties of blood cells as biomarkers for the diagnosis and follow-up of Long-COVID (Long-disCOVer),,,2023,Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.,97354.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Innovation,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Disease pathogenesis | Post acute and long term health consequences,2022 +P25163,01EP2201,National Clinical Study Group (NKSG) Post-Covid Syndrome and ME/CFS,,,2024,Charité - Universitätsmedizin Berlin,9683708.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25164,16LW0311,Alternativemethods: Animal-free Secondary Antibodies (AniSAn),,,2026,Leibniz Universität Hannover,389631.56,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P25165,13GW0595B,Collaborative project: Detection of multiple parameters of the immune response in viral diseases (VirusDual) - Subproject: Establishment of a molecular biological method for the highly sensitive detection of antibodies in blood serum,,,2026,Actome GmbH,450711.82,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P25166,01KU2309,UriCoV - Urinary peptidomic patterns as biomarkers of Long COVID syndrome,,,2025,Klinikum St. Georg gGmbH,249768.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25167,01KA2304,InnoCOV- Innovation policy for resilient biomedical R&D systems: Lessons learnt from the innovation response to the COVID-19 pandemic,,,2025,Universität Heidelberg,213626.7,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Policies for public health, disease control & community resilience",Policy research and interventions,2023 +P25168,01UJ2311CY,Collaborative project: GDR past and mental health: risk and protective factors (DDR-Psych). Sub-project: Individual social and regional socioeconomic determinants of mental health and COVID-19 vaccination status in East and West Germany,,,2025,Robert Koch-Institut (RKI),157718.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions,2023 +P25169,16SV9174,KoVit: Contactless vital parameter recording for objective post-Covid monitoring to support medical diagnostics,,,2025,MedEcon Ruhr GmbH,79227.02,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2023 +P25170,16SV9175,KoVit: Contactless vital parameter recording for objective post-Covid monitoring to support medical diagnostics,,,2025,FIMO Health GmbH,194825.53,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2023 +P25171,16SV9173,KoVit: Contactless vital parameter recording for objective post-Covid monitoring to support medical diagnostics,,,2025,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,354001.96,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2023 +P25172,13GW0664A,"KMU-innovativ - Collaborative project: Lateral flow test system at the point of care for the detection of organ infestation after COVID-19 (VIROTEC), Subproject A",,,2026,Therawis Diagnostics GmbH,589364.16,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Post acute and long term health consequences,2024 +P25173,13GW0664B,"KMU-innovativ - Collaborative project: Lateral flow test system at the point of care for the detection of organ infestation after COVID-19 (VIROTEC), Subproject B",,,2026,Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.,526671.2,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2024 +P25174,13GW0664D,"KMU-innovativ - Collaborative project: Lateral flow test system at the point of care for the detection of organ infestation after COVID-19 (VIROTEC), Subproject D",,,2026,RKT Rodinger Kunststoff-Technik GmbH,78873.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2024 +P25175,13GW0664C,"KMU-innovativ - Collaborative project: Lateral flow test system at the point of care for the detection of organ infestation after COVID-19 (VIROTEC), Subproject C",,,2026,Klinikum rechts der Isar der Technischen Universität München,346288.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2024 +P25176,031B0955B,Rapid development Corona rapid test for simple application (CoSE); Subproject B,Rapid development Corona rapid test for simple application (CoSE); Subproject B,,2021,Senova Gesellschaft für Biowissenschaft und Technik mbH,306680.19,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25177,031B0955A,Rapid development Corona rapid test for simple application (CoSE); Subproject A,Rapid development Corona rapid test for simple application (CoSE); Subproject A,,2021,NH DYEAGNOSTICS GmbH,567143.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25178,031B0955D,Rapid development Corona rapid test for simple application (CoSE); Subproject D,Rapid development Corona rapid test for simple application (CoSE); Subproject D,,2021,"fzmb GmbH, Forschungszentrum für Medizintechnik und Biotechnologie",892599.96,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25179,01KI2006C,RAPID: Identification of virus-host interactions at the protein level and construction of test systems.,RAPID: Identification of virus-host interactions at the protein level and construction of test systems.,,2023,Ludwig-Maximilians-Universität München,66820.32,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2020 +P25180,01IS20S20,Software Sprint - Individual projects: LabHive - Effective distribution of test resources,,,2020,LabHive GbR,52703.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25182,01KI20521C,CancerCOVID - Resource Allocation for Cancer Care in the Context of Sars-CoV-2 - Colon Cancer Care Subproject.,"The outbreak of Sars-CoV-2 triggered unprecedented preparations for the care of patients with COVID-19 (1). In addition, access to hospitals and outpatient clinics was restricted due to specific hygiene regulations. Allocation of health resources in times of pandemic has potential clinical and ethically relevant implications for non-COVID-19 patients (2, 3). However, a systematic assessment of evidence and interdisciplinary analyses regarding ethical and social aspects related to care for non-COVID-19 patients during the pandemic is missing. The interdisciplinary CancerCOVID consortium will analyse possible implications of the outbreak of Sars-CoV-2 for the access, process and outcomes of care, with a focus on patients with cancer in Germany. For this purpose we will analyse quantitative data derived from the registry of colon cancer centres and data from the statutory health insurance on the care of patients with cancer, diabetes and coronary heart disease. In addition we will explore the ethical and psycho-social challenges perceived by patients and health professionals during the pandemic by means of semi-structured interviews. Based on the findings and together with major decision makers in the German healthcare system we will develop guidance for clinical and health policy decisions about priority settings regarding cancer care in times of pandemics and comparable major events.",,2022,Ruhr-Universität Bochum,143991.48,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Health Personnel,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2020 +P25183,01KI20198A,"GI-SARS-2 - Gastrointestinal manifestations of SARS-CoV-2, relevance to viral replication, spread and pathogenesis.","Although there are accumulating evidence that the intestinal epithelium is infected by SARS-CoV-2, the importance of this enteric phase for virus-induced pathologies, spreading and prognosis remain unknown. Here, we will engage in the comprehensive analysis of SARS-CoV-2 life-cycle in the human intestinal epithelium. (1) we will evaluate if there are infectious virus particles in stool. (2) we will develop standardized protocols to establish a robust measure for enteric virus shedding. (3) in organoids models, we will characterize how SARS-CoV-2 infects, replicates and is released from intestinal epithelial cells. This will provide the molecular basis of the enteric lifecycle and will enable us to determine the origin of the enteric phase (fecal/oral transmission vs. spreading from lung to gut). To these goals, we will exploit a pipeline combining single cell sequencing and spatial transcriptomics which we developed to study host-virus interaction. Combined with in-situ measurement of immune response in biopsies, we will define whether exacerbated gut inflammation contributes to the lung pathology observed in patients through cytokine storm-induced cytopathic effects. We anticipate that understanding the enteric phase of SARS-CoV-2 will provide us with critical pieces of evidence to outline novel perspectives to treat the disease and eradicate the virus. Most importantly, quantifying the relevance of fecal transmission and its link to SARS-CoV-2 etiology is urgently needed to implement epidemiological and societal measures aiming at monitoring and controlling the virus.",,2021,Universität Heidelberg,249557.49,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis,2020 +P25184,01KI20241B,"BIO-PROTECT-Mask - Evaluation of lung function, exercise capacity, and breathlessness associated with wearing certified masks, homemade masks, and newly developed masks-a risk-benefit evaluation in high-risk patients with chronic lung disease (MaskCFD).","Because of the outbreak of COVID-19, many countries have recently regulated by law or strongly advice that face masks should be worn in distinct public environments in order to prevent further spreading of SARS-CoV-2. While there is a vivid discussion on the different types of certified or home-made masks and possible shortages in the supply chains, previous studies in other virus epidemics (influenza) indicate that compliance with wearing face masks and wearing time are the strongest predictors with respect a successful public healthcare intervention. One explanation for low wearing time might be the high pressure loss of most certified face masks that makes breathing difficult and wearing uncomfortable. Especially high-risk patients with chronic lung diseases may suffer from additional breathlessness while requiring a particularly high level of protection. Shortness of certified masks results in low-evidence recommendations for the use of home-made masks, however, it remains unclear whether the used materials provide reasonable protection against the transmission. In-depth studies that identify the best materials and layering are lacking, although experiments that would identify innovative materials with an optimal relationship of bioaerosol deposition and pressure loss might be a solution to improve the real-world effectiveness of mask wearing in public.",,2022,Hochschule Heilbronn,214534.64,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P25185,01KI20241C,"BIO-PROTECT-Mask - Bio-aerosol protection by ready-to-use and optimized protective masks for high and low risk patients - Investigation, design and prototyping of protective masks with optimized breathing resistance and comfort (MaskPRO)","Because of the outbreak of COVID-19, many countries have recently regulated by law or strongly advice that face masks should be worn in distinct public environments in order to prevent further spreading of SARS-CoV-2. While there is a vivid discussion on the different types of certified or home-made masks and possible shortages in the supply chains, previous studies in other virus epidemics (influenza) indicate that compliance with wearing face masks and wearing time are the strongest predictors with respect a successful public healthcare intervention. One explanation for low wearing time might be the high pressure loss of most certified face masks that makes breathing difficult and wearing uncomfortable. Especially high-risk patients with chronic lung diseases may suffer from additional breathlessness while requiring a particularly high level of protection. Shortness of certified masks results in low-evidence recommendations for the use of home-made masks, however, it remains unclear whether the used materials provide reasonable protection against the transmission. In-depth studies that identify the best materials and layering are lacking, although experiments that would identify innovative materials with an optimal relationship of bioaerosol deposition and pressure loss might be a solution to improve the real-world effectiveness of mask wearing in public.",,2021,Junker-Filter GmbH,99116.55,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P25186,01KI20703,"ACE-mR-CoV - Development, testing and production of a SARS-CoV-2 vaccine based on mRNA technology.","The project encompasses all activities required for the approval and dissemination of a vaccine against SARS-CoV-2. In particular, this includes a broad phase I-III clinical programme to ensure the safety and effectiveness of the vaccine. In addition, the project includes the non-clinical studies relevant for approval as well as the increase of production capacities in order to make the vaccine available to a large part of the population in a timely manner after approval. After completion and evaluation of the ongoing phase I trial in autumn 2020, the clinical trials of phases II and III will follow. The goal of the vaccine development is a conditional approval of the vaccine by the European Medicines Agency (EMA), if possible already at the beginning of 2021, followed by the regular approval in the second half of 2021. In parallel, the production capacities for vaccine manufacturing will be expanded.",,2021,CureVac AG,231659253.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I | Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Vaccines research, development and implementation",Phase 1 clinical trial | Phase 2 clinical trial | Phase 3 clinical trial | Vaccine logistics and supply chains and distribution strategies,2020 +P25187,03COV13B,"CORONA - TOPAS-COVID19 - Physiologically optimised protective masks suitable for everyday use, Subproject B",,,2022,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,244878.02,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P25188,03COV20A,CORONA - VALIDATE-Dx - Validation/standardisation tool for antibody tests and generation of binding standards for the comparison of tests; Subproject A,,,2021,in.vent Diagnostica GmbH,288283.26,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25189,03COV20B,CORONA - VALIDATE-Dx - Validation/standardisation tool for antibody tests and generation of binding standards for the comparison of tests; Subproject B,,,2021,KH Labor GmbH,257846.64,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25190,03COV05D,"Corona - PlaVir - Plasma-based disinfection of medical supplies with a focus on medical protective equipment, Subproject D",,,2024,HygCen Germany GmbH,485445.93,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25191,03COV10A,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject A",,,2023,Universitätsmedizin Greifswald,348596.27,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25192,03COV10C,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject C",,,2023,Charité - Universitätsmedizin Berlin,597226.55,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25193,03COV10B,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject B",,,2023,Friedrich-Loeffler-Institut Bundesforschungsinstitut für Tiergesundheit,209100,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25194,03COV10G,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject G",,,2023,Freie Universität Berlin,206307.9,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25195,03COV23C,CORONA - BEAD-Dx -Bead-based Multiplex-Assay; Subproject C,,,2022,Universität Potsdam,107363.58,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25196,03COV10D,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject D",,,2023,Technische Universität Berlin,650397.54,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25197,03COV09C,CORONA - 3Dsensation - 3DecontaminAid; TP3: Klinische Anwendung,,,2024,Universitätsklinikum Jena,417860.39,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25198,03COV09B,CORONA - 3Dsensation - 3DecontaminAid; TP2: Infektionsdiagnostik - InDi,,,2024,Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.V. Hans-Knöll-Institut,590826.94,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25199,03COV09A,CORONA - 3Dsensation - 3DecontaminAid; TP1: Multimodale 3D-Sensorik - MuSe,,,2023,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,2046505.06,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25200,03COV10F,"CORONA - CORSA - Collaborative project - Inactivation of SARS-CoV-2 by UVC light and tolerability for humans, Subproject F",,,2023,ams-OSRAM International GmbH,984000,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25201,01KA2028,Enhance TB Sequel: additional support for TBSequel to address the challenges and additional costs associated with the new global pandemic situation caused by SARS-CoV 2.,"Sub-project of Prof. Schaible's working group at the FZB is located in work package 3. The focus of this work package is the integration of new research questions that investigate the influence of an additional SARS-Cov 2 infection in an existing TB disease. Both diseases place a considerable burden on lung function, mainly due to the inflammatory processes in the lungs caused by the pathogens. It is planned to examine plasma samples from TB patients with or without SARS-Cov 2 infection for the presence of 300 inflammation-relevant proteins (O-linked arrays) or in a multi-cytokine array for the presence of inflammation-relevant cytokines such as Th17 factors or type I interferons. Patient samples will be collected at all TBSequel partner institutes. It is expected that markers (plasma proteins or cytokines) will be found that are related to the degree of recovery of lung function after TB therapy.",,2022,Forschungszentrum Borstel Leibniz Lungenzentrum,59532,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Prognostic factors for disease severity,2021 +P25202,16ME0373K,Collaborative project: Miniaturised electronic system for the rapid detection of viruses and bacteria in disinfectant dispensers - GeDeSens2Virus -,,,2024,OPHARDT HYGIENE-TECHNIK GmbH + Co. KG,422972.78,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25203,16ME0375,Collaborative project: Miniaturised electronic system for the rapid detection of viruses and bacteria in disinfectant dispensers - GeDeSens2Virus -,,,2024,Albert-Ludwigs-Universität Freiburg,480192,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25204,13GW0542C,"Collaborative project: Decision support for health authorities using risk modelling to combat the pandemic (EsteR), Subproject C",,,2022,Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS GmbH,147353.17,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Disease surveillance & mapping,2021 +P25205,13GW0542A,"Collaborative project: Decision support for health authorities using risk modelling to combat the pandemic (EsteR), Subproject A",,,2022,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,195838.3,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Policy research and interventions,2021 +P25206,13GW0545A,"Collaborative project: Flexible point-of-care rapid test for the diagnosis of respiratory pathogens (ID_PoC), Subproject B",,,2022,FRIZ Biochem GmbH,508813.06,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25207,13GW0545B,"Collaborative project: Flexible point-of-care rapid test for the diagnosis of respiratory pathogens (ID_PoC), Subproject B",,,2022,Technische Universität Dresden,206460.24,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Other,,,,,,,,,Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25208,02WRS1621A,"RiSKWa - Joint project COVIDready: Decentralised SARS-CoV-2 monitoring in wastewater: Development of a validated analysis method for wastewater technology laboratories at sewage treatment plants, Subproject A",,,2023,Forschungsinstitut für Wasserwirtschaft und Klimazukunft an der RWTH Aachen e. V.,349148.14,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2021 +P25209,02WRS1621B,"RiSKWa - Joint project COVIDready: Decentralised SARS-CoV-2 monitoring in wastewater: Development of a validated analysis method for wastewater technology laboratories at sewage treatment plants, Subproject B",,,2023,Rheinisch-Westfälische Technische Hochschule Aachen,659502.72,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2021 +P25210,02WRS1621C,"RiSKWa - Joint project COVIDready: Decentralised SARS-CoV-2 monitoring in wastewater: Development of a validated analysis method for wastewater technology laboratories at sewage treatment plants, Subproject C",,,2023,Johann Wolfgang Goethe-Universität Frankfurt am Main,440876.29,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2021 +P25211,02WRS1621D,"RiSKWa - Joint project COVIDready: Decentralised SARS-CoV-2 monitoring in wastewater: Development of a validated analysis method for wastewater technology laboratories at sewage treatment plants, Subproject D",,,2023,Lippeverband,319171.52,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2021 +P25212,01DH21022B,"Collaborative project: ""Molecular point-of-care microfluidic system for rapid diagnostics of viral infections"" - Subproject B",,,2024,FRIZ Biochem GmbH,58003.97,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25213,01DH21022A,"Collaborative project: ""Molecular point-of-care microfluidic system for rapid diagnostics of viral infections"" - Subproject A",,,2024,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,216318.83,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25214,01KA2111A,Sustainability of the Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) for evidence-based health research and care in sub-Saharan Africa,,,2023,Ludwig-Maximilians-Universität München,362364.29,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health information systems,2021 +P25216,13GW0590A,Collaborative project: High-throughput analysis of virus-specific memory B cells to determine individual immune responses (B cell immune) - Subproject A,,,2025,LPKF Laser & Electronics SE,350131,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25217,031L0290B,CompLS -Round 4 - Collaborative project: DeepTCR - Development of advanced deep learning approaches to analyse the T cell immune response at the single cell level - Subproject B,,,2024,Friedrich-Alexander-Universität Erlangen-Nürnberg,171828.21,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25218,031L0293B,CompLS - Round 4 - Collaborative project: EMUNE - Invertible neural networks for an improved understanding of infectious diseases - Subproject B,,,2024,Klinikum der Universität München,132210,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25219,031L0293C,CompLS - Round 4 - Collaborative project: EMUNE - Invertible neural networks for an improved understanding of infectious diseases - Subproject C,,,2024,Rheinische Friedrich-Wilhelms-Universität Bonn,319098.09,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25220,031L0290A,CompLS -Round 4 - Collaborative project: DeepTCR - Development of advanced deep learning approaches to analyse the T cell immune response at the single cell level - Subproject A,,,2024,Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH),261220.31,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25221,031L0293A,CompLS - Round 4 - Collaborative project: EMUNE - Invertible neural networks for an improved understanding of infectious diseases - Subproject A,,,2025,Universität Heidelberg,536820.7,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25222,031L0292B,CompLS - Round 4 - Collaborative project: GENImmune - Generic methods for modelling host-pathogen interactions applied to efficient immunisation against SARS-CoV-2 - Subproject B,,,2023,PEPperPRINT GmbH,162186.92,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P25223,13GW0590D,Collaborative project: High-throughput analysis of virus-specific memory B cells to determine individual immune responses (B cell immune) - Subproject D,,,2025,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,580700,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25224,13GW0597A,Collaborative project: UVC air sterilisation in indoor spaces (BeCoLe) - Subproject A,,,2025,S & P Sahlmann - Planungsgesellschaft für Gebäudetechnik mbH,444906.8,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P25225,13GW0597I,Collaborative project: UVC air sterilisation in indoor spaces (BeCoLe) - Subproject I,,,2023,Virobuster International GmbH,263913,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P25226,13GW0597D,Collaborative project: UVC air sterilisation in indoor spaces (BeCoLe) - Subproject D,,,2025,"Hochschule für Technik, Wirtschaft und Kultur Leipzig",302203.2,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P25227,01EP2108C,"reCOVer - Autoantibodies against G protein-coupled receptors as a harmful agent for the microcirculation as a cause of symptom persistence in ""Long-COVID"" - Subproject C",,,2023,Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.,103322.42,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2022 +P25228,01EP2108A,"reCOVer - Autoantibodies against G protein-coupled receptors as a harmful agent for the microcirculation as a cause of symptom persistence in ""Long-COVID"" - Subproject A",,,2024,Friedrich-Alexander-Universität Erlangen-Nürnberg,991846.28,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2022 +P25229,01EP2110A,LoCoVICF - Restrictions on participation and quality of life as well as care needs of affected persons in the healthcare system with late symptoms after SARS-CoV-2 infection: A multi-perspective analysis,,,2024,Universitätsklinikum Hamburg-Eppendorf,470767.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Community engagement,2022 +P25230,01EP2106,IDEpiCo - Immune dysregulation and epigenetic memory in post-COVID syndromes,,,2024,Universität zu Köln,561886.39,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2022 +P25231,031L0292E,CompLS - Round 4 - Collaborative project: GENImmune - Generic methods for modelling host-pathogen interactions applied to efficient immunisation against SARS-CoV-2 - Subproject E,,,2023,Technische Universität München,213988.73,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P25232,13GW0600A,Collaborative project: Modelling the SARS-CoV-2 infection process to secure and optimise health care in the model region Halle/Saale (MODELIGEV) - Subproject A,,,2025,TWT GmbH Science & Innovation,513721.98,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Health Systems Research,Disease transmission dynamics | Health service delivery,2023 +P25233,13GW0600B,Collaborative project: Modelling the SARS-CoV-2 infection process to secure and optimise health care in the model region Halle/Saale (MODELIGEV) - Subproject B,,,2025,Martin-Luther-Universität Halle-Wittenberg,408581.64,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies | Health Systems Research,Disease transmission dynamics | Health service delivery,2023 +P25234,13GW0593D,Collaborative project: On-site monitoring and therapy control of infections using circulating free DNA (EPI-CARE) - Subproject D,,,2025,Johannes Gutenberg-Universität Mainz,558306,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations",2022 +P25235,13GW0590C,Collaborative project: High-throughput analysis of virus-specific memory B cells to determine individual immune responses (B cell immune) - Subproject C,,,2025,Medizinische Hochschule Hannover (MHH),578484,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25236,13GW0622,Mass spectrometric rapid diagnostics of respiratory viruses in saliva and gargle solution (VirMScan),,,2025,Leibniz-Institut für Virologie (LIV),4026848,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Other,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P25239,031L0299A,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject A,,,2025,Martin-Luther-Universität Halle-Wittenberg,621600.76,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2022 +P25240,031L0299B,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject B,,,2025,Universität Münster,280848.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2022 +P25241,031L0299C,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject C,,,2025,Freie Universität Berlin,58450.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2022 +P25242,031L0299D,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subprojectd,,,2025,Universität zu Lübeck,307413.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25243,031L0299E,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject E,,,2025,Universität Leipzig,236389.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2022 +P25244,031L0299F,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject JF,,,2025,Universität Trier,385887.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25245,031L0299G,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject G,,,2025,Rheinland-Pfälzische Technische Universität Kaiserslautern-Landau,284291.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25246,031L0299H,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject H,,,2025,Helmholtz-Zentrum für Infektionsforschung GmbH,112445.78,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25247,031L0299J,Modelling network: OptimAgent - Optimised strategies for epidemic control in highly heterogeneous populations - Subproject J,,,2025,Universität Münster,344827.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25248,031L0298A,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject A,,,2025,Helmholtz-Zentrum für Infektionsforschung GmbH,437505.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25249,031L0298D,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject D,,,2025,Martin-Luther-Universität Halle-Wittenberg,109039.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25250,031L0298E,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject E,,,2025,Universität zu Köln,68935.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25251,031L0298F,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject F,,,2025,Universität Münster,109058.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25252,031L0298J,Modelling network: RESPINOW - Impact of non-pharmaceutical interventions on the burden of respiratory infections during and after the pandemic - Subproject J,,,2025,Karlsruher Institut für Technologie (Universitätsaufgabe),163993.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Epidemiological studies,Impact/ effectiveness of control measures,2022 +P25253,13GW0604C,KMU-innovativ - Collaborative project: Rapid test for neutralising antibodies against SARS-CoV-2 (NanoNeutVir) - Subproject C,,,2025,Universität Regensburg,423696,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25254,13GW0604D,KMU-innovativ - Collaborative project: Rapid test for neutralising antibodies against SARS-CoV-2 (NanoNeutVir) - Subproject D,,,2025,Universitätsklinikum Regensburg,261143.4,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25255,01EJ2204A,"IMMME - Elucidation of the immunological pathomechanisms of post-infectious chronic fatigue syndrome (ME/CFS) - establishment of a biobank, analyses of specific autoantibodies and bioinformatic identification of potential biomarkers",,,2025,Charité - Universitätsmedizin Berlin,690467.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Post acute and long term health consequences,2022 +P25258,03ZU1201AC,"CNATM: Chemically modified nucleosides, nucleotides and oligonucleotides as therapeutics and vaccines (joint project 1) - C",,,2026,baseclick GmbH,428986.8,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2023 +P25259,03ZU1201AK,"CNATM: Chemically modified nucleosides, nucleotides and oligonucleotides as therapeutics and vaccines (joint project 1) - K",,,2026,siTOOLs Biotech GmbH,164956.77,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",,2023 +P25260,01KI2309,Arbo-flipGFP - Generation of activatable fluorescent insect reporter cells for the detection of arbovirus infections,,,2024,Otto-von-Guericke-Universität Magdeburg,202230.28,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Crimean-Congo haemorrhagic fever | Rift Valley Fever | Zika virus disease,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors,,2023 +P25261,031L0293E,CompLS - Round 4 - Collaborative project: EMUNE - Invertible Neural Networks for an Improved Understanding of Infectious Diseases - Subproject E,,,2025,Friedrich-Alexander-Universität Erlangen-Nürnberg,253569.93,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2023 +P25262,16SV9158,"TeleDiagAtSmart: Telemedical tool for networked, contactless diagnostics for post-COVID syndrome using hybrid symptom recording and voice input",,,2025,Universität Siegen,350122.49,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25263,16SV9159,"TeleDiagAtSmart: Telemedical tool for networked, contactless diagnostics for post-COVID syndrome using hybrid symptom recording and voice input",,,2025,Universitätsklinikum Aachen,785353.4,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25264,16SV9164,"Post-COVID_E-Doc: Realisation and research of a contactless, adaptive, adaptive and hybrid post-COVID check-up and information system",,,2025,Universität Duisburg-Essen,299253.45,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P25265,16SV9157,"TeleDiagAtSmart: Telemedical tool for networked, contactless diagnostics for post-COVID syndrome using hybrid symptom recording and voice input",,,2025,ALMA PHIL GmbH,357739.2,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,Digital Health,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25266,01QE2315A,Collaborative project: Theranostic concepts for the diagnosis and treatment of hyperinflammation syndrome - Subproject: Synthesis and effect analysis of theranostics in inflammatory disease models,"About 15% of patients infected with the newly identified SARS-CoV-2 virus develop a critical form of the disease characterized by respiratory and/or multi-organ failure due to hyperinflammation as an overreaction of the innate nonspecific immune system against the unknown pathogen. The experiments and models described in our HYPERFLAME proposal will provide valuable insights in this context and pave the way for the possible development of an innovative approach to effectively and early detect, monitor and treat hyperinflammation syndrome. The aim of subproject 1 ""Synthesis and effect analysis of theranostics in inflammatory disease models"" of the HYPERFLAME joint project is to build a chemical platform with functionalized dendritic polymers for the development of active substances for therapy and diagnosis (theranostics) of hyperinflammatory syndrome in virus-related infections and autoimmune diseases. This represents an innovation in this field and will also lead to improved tools for preclinical and clinical research.",,2026,nanoPET Pharma GmbH,338975.29,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,"Supportive care, processes of care and management",2023 +P25269,01KI2006F,RAPID: Pre-pandemic risk assessment based on human lung tissue (MERS) - subproject F,"he Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory infections. The pathogen was discovered in 2012 during a fatal viral pneumonia in Saudi Arabia. Specific treatment options do not yet exist. Up to 30 percent of those infected die. The infection is usually rare. It is usually acquired through contact with dromedaries, which are one of the main livestock in the Middle East and parts of Africa. However, human-to-human transmission does occur and then leads to major outbreaks. The virus is so far not well adapted to humans as hosts. However, mutations that could cause a higher risk of infection and subsequently a pandemic are feared. MERS-CoV is therefore currently one of the most threatening, so-called ""pre-pandemic"" infectious agents. For efficient control of pre-pandemic pathogens, it is essential that the public health service arrives at solid assessments of outbreak progress. The research consortium therefore aims to use the example of MERS-CoV to address constraints and research questions for the public health service. In particular, approaches are to be developed that enable science and public health to detect the outbreak of pre-pandemic viruses earlier and to prevent their transformation into pandemic pathogens. In addition, work is to be done on a vaccine for host animals and humans in cooperation with partners in Saudi Arabia. The network is part of the National Research Network on Zoonotic Infectious Diseases. In particular, the ""One Health"" approach (simultaneous consideration of human and veterinary aspects) and the transfer of results into the application of the public health service are being pursued",,2021,Robert Koch-Institut (RKI),75552.34,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Vaccines research, development and implementation",Animal source and routes of transmission | Disease transmission dynamics | Pre-clinical studies,2020 +P25270,01KI2006G,RAPID: Conduct studies to evaluate the immunogenicity and protective efficacy of MVA-MERS-S vaccines in the camel - Subproject G,"he Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory infections. The pathogen was discovered in 2012 during a fatal viral pneumonia in Saudi Arabia. Specific treatment options do not yet exist. Up to 30 percent of those infected die. The infection is usually rare. It is usually acquired through contact with dromedaries, which are one of the main livestock in the Middle East and parts of Africa. However, human-to-human transmission does occur and then leads to major outbreaks. The virus is so far not well adapted to humans as hosts. However, mutations that could cause a higher risk of infection and subsequently a pandemic are feared. MERS-CoV is therefore currently one of the most threatening, so-called ""pre-pandemic"" infectious agents. For efficient control of pre-pandemic pathogens, it is essential that the public health service arrives at solid assessments of outbreak progress. The research consortium therefore aims to use the example of MERS-CoV to address constraints and research questions for the public health service. In particular, approaches are to be developed that enable science and public health to detect the outbreak of pre-pandemic viruses earlier and to prevent their transformation into pandemic pathogens. In addition, work is to be done on a vaccine for host animals and humans in cooperation with partners in Saudi Arabia. The network is part of the National Research Network on Zoonotic Infectious Diseases. In particular, the ""One Health"" approach (simultaneous consideration of human and veterinary aspects) and the transfer of results into the application of the public health service are being pursued",,2023,Stiftung Tierärztliche Hochschule Hannover,112658.42,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Animal and environmental research and research on diseases vectors | Epidemiological studies | Vaccines research, development and implementation",Animal source and routes of transmission | Disease transmission dynamics | Pre-clinical studies,2020 +P25271,01KI2210,Bat-FIM - The role of IL33 Signaling for the immune tolerance against filovirus-infection in Bats.,"Bats are natural reservoirs for several viral zoonotic agents, including highly pathogenic filoviruses such as Marburg virus (MARV) and Ebola virus, the causative agents of viral hemorrhagic fever in humans. The reservoir competence of bats depends on their ability to harbor viruses without symptoms or pathology. One proposed mechanism for their reservoir competence is ""immune tolerance,"" which involves a tightly controlled antiviral immune response and suppressed proinflammatory signaling. In mammals, myeloid cells such as dendritic cells (DC) and macrophages (Mph) are professional antigen-presenting cells (APC) that control the host immune response to infection. Both DC and Mph are also important initial targets of filoviruses. Importantly, filovirus infections lead to disruption of cell responses of human DC and Mph. In contrast, bat DCs from the natural MARV reservoir R. aegyptiacus were recently shown to elicit a distinct antiviral immune response against MARV and significantly suppress proinflammatory responses such as the cytokine IL-33. Whether bat Mph exhibit a similarly suppressed IL-33 response as bat DCs and whether, in contrast, human myeloid cells exhibit increased IL-33 release following infection with MARV or EBOV is unknown. This project therefore aims to differentiate bat-derived Mph from two known bat reservoirs of filoviruses and to compare for the first time the IL-33 responses of bat DCs and Mphs to MARV and EBOV in vitro with those of humans, providing a unique opportunity to understand the underlying differences in immune cell responses of humans and bats to two of the highly pathogenic viral zoonoses.",,2023,Robert Koch-Institut (RKI),142997.23,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Animal and environmental research and research on diseases vectors | Clinical characterisation and management,Animal source and routes of transmission | Disease pathogenesis,2022 +P25272,01KA1920,PREPARE-GERMANY: Pre-exposure prophylaxis for individuals with potential occupational risk of exposure to Ebola virus.,,,2024,Universitätsklinikum Hamburg-Eppendorf (UKE),611827,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Filoviridae,,,,,,,,,Ebola virus disease,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management",2020 +P25273,13N15825,Collaborative project: FISH in field (FIELD); Subproject: FELD-PACS,,,2024,NEXUS / CHILI GmbH,244418.96,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25274,16GW0274,Target validation: validation of targeted lipid addressing as a new strategy for broad-spectrum antiviral agents (LABoVIR) - structural biology and mechanism of action.,,,2022,Technische Universität Berlin,302026.37,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2020 +P25275,01QE2001B,"Joint project: The first broad-spectrum active agent against the potentially pandemic flaviviruses Zika, Dengue and West Nile Virus; Subproject: Analytical methods for the quantification of flaviviral infections and the development of drug candidates",,,2023,chimera biotec GmbH,268104.73,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +P25276,01QE2001C,"Joint project: The first broad-spectrum active agent against the potentially pandemic flaviviruses Zika, Dengue and West Nile Virus; Subproject: Development of infection models for the analysis of antiviral effects",,,2023,Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein,272029,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P25277,01KA2213,TOWARDS AN AFRICAN PLATFORM FOR CONGENITAL ABNORMALITIES,,,2024,Centre de Recherche en Santé de Nouna (CRSN),51587.91,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2022 +P25278,16LW0366,Alternative methods: Establishment of cell and organoid cultures for the implementation of the 3Rs in infection research with non-human primates 2.0 (ZellOrKult-2),,,2025,Deutsches Primatenzentrum Gesellschaft mit beschränkter Haftung - Leibniz-Institut für Primatenforschung,323378.66,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Disease models,2023 +P25279,01DN23003,"Collaborative project: Aptamer-based strategies for the development of novel biotechnological tools against arboviruses (ABSarbo) - Subproject: Plasmonic, aptamer-based sensor for the detection of arboviruses",,,2026,Leibniz-Institut für Photonische Technologien e.V. (Engl.Leibniz Institute of Photonic Technology),106954.79,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Bunyaviridae | Flaviviridae,,,,,,,,,Unspecified,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P25280,HZI2021Z41,Animal facility for testing vaccines and antivirals against emerging infections under BSL-3/4 conditions.,,,2026,Paul-Ehrlich-Institut Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel,379252.72,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Novel Pathogen,,,,,,,,,Disease X,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,,,2021 +P25281,01KI2001,IVIBAK - Does an influenza A virus-triggered immune response induce growth factors for bacterial co-infections?,,,2023,Stiftung Tierärztliche Hochschule Hannover,263062.55,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,Clinical characterisation and management,Disease pathogenesis,2020 +P25282,13GW0478B,KMU-innovativ - Collaborative project: Rapid indicator for influenza (influenza chewing gum) - Sub-project: Collection and characterisation of saliva samples and clinical data,,,2023,Universitätsklinikum Würzburg,63176.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25283,13GW0478A,KMU-innovativ - Collaborative project: Rapid indicator for influenza (influenza chewing gum) - Sub-project: Research into the sensor chewing gum,,,2023,3a-diagnostics GmbH,48400,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25284,13GW0478C,KMU-innovativ - Collaborative project: Rapid indicator for influenza (influenza chewing gum) - Sub-project: Synthesis and testing of the sensor,,,2023,Julius-Maximilians-Universität Würzburg,124320.24,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF),Germany,Europe,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P25285,COV0333,AERosolisation And Transmission Of SARS-CoV-2 in Healthcare Settings (AERATOR),"Aerosolisation of SARS-CoV-2 during clinical procedures is a major concern. The safe resumption of essential NHS services is impaired by the need to mitigate the theoretical risk of cross infection from procedural aerosolisation. This includes extensive pre- operative planning, use of personal protective equipment (PPE) throughout, and delays in patient/staff movement before, during, and after the procedure. There is currently little to no evidence on aerosolisation risk for many procedures, hampering national guidance and greatly reducing NHS capacity. The AERATOR study will address a critical gap in evidence by quantifying the concentration, size and temporal and spatial dynamics of aerosols produced during routine medical & surgical procedures in different environments. This will focus on five clinical specialties particularly impacted by procedural aerosolisation: dental, orthopaedic, respiratory, critical care and ophthalmology. This work comprises three workstreams: Workstream 1: Within the Bristol Aerosol Research Centre (BARC) we will rapidly (within 4 weeks) validate instruments to study aerosolisation in clinical settings. Workstream 2: Instruments will be moved into clinical settings and, using multiple instruments and sampling techniques, will measure aerosolisation dynamics and size across time and space. Workstream 3: By using novel equipment, only available within Bristol, to levitate virus within a CL3 laboratory, we will investigate the survival of SARS-CoV-2 in aerosol particles and determine its infectivity. The information gathered in this study will allow us to inform hospital trusts, policy makers and Public Health England regarding the safe and maximally efficient NHS working across multiple specialties.",,2023,N/A,822076.2,Viruses | Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2020 +P25286,COV-LT-0040,REACT Long COVID (REACT-LC),"Some people with COVID-19 experience symptoms for several weeks or months (Long COVID), while others have a short illness or no symptoms. We have very little understanding of why this happens. Most research on Long COVID has been with hospitalised patients. Our study will involve people in the community who have taken part in the REACT study of the virus that causes COVID-19. Over 30,000 people from REACT have had positive test results and they, plus a sample of 90,000 who tested negative, will be invited to take part in the new study. These 120,000 people will be sent a survey about their health, symptoms and experiences since the test; we will also link to health records. Participants with Long COVID will be asked to join a panel to provide regular updates on their symptoms; 60 will be invited for in-depth interview. We will repeat the survey of the 120,000 after 18 months to track symptoms and their health. We will work closely with a panel of public advisers including people with Long COVID to develop a set of patient-reported outcomes that reflect the symptoms that are most important. We will also invite up to 8,000 people with positive tests, including at least 4,000 with Long COVID, to an assessment centre for health tests and samples to test for genetic and other biological markers. Around 2,000 will attend a follow-up visit after 4-6 months for repeated measurements and samples. The data from these studies will be analysed to find factors affecting why some people get Long COVID and others don t. The biological studies will help us understand mechanisms causing persistent symptoms and may point to possible treatments. Through the surveys and work with participants we will understand why some people are more vulnerable and how best to support them.",,2024,N/A,7556594.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25287,COV-LT2-0004,Development of a robust T cell assay to retrospectively diagnose SARS-CoV-2 infection and T cell cytokine release assay as diagnostic and monitoring assay in Long COVID patients,"The current COVID-19 pandemic caused by coronavirus (SARS-CoV-2), has already infected close to 150 million people with over 3 million deaths worldwide. Unfortunately, a significant proportion of people continue to experience distressing and life altering symptoms several months after the initial illness. People with persistent symptoms are currently classified as having Long COVID. Diagnosis of Long COVID is hampered especially in the group of non-hospitalised patients as the majority had asymptomatic to mild infection hence less likely to have generated antibodies against coronavirus and antibody tests miss a significant proportion of patients (~30%). We therefore propose to develop a COVID diagnostic assay that is based on detecting the aspect of the body s immune response (T cell response) that is triggered in this case in response to coronavirus and is most likely to be detected several months to years following infection. The diagnostic assay will be used in clinical setting. This research proposal was birthed in consultation with patients suffering from Long COVID since the initial wave. We set up a Long COVID clinic for non-hospitalised patients in May 2020 at Addenbrooke s, to provide better clinical care and enroll patients into the Cambridge COVID NIHR BioResource. The enrolled patients had bloods taken and we have preliminary results that show our study s feasibility and we want to scale this to an assay that will be able to process high volumes of samples with quick turnaround of results. We will continue to enroll patients and follow them up every 3 months for up to 18 months. We will disseminate our research findings to the public and patients via bulletins to GPs, patient information leaflets generated by the Addenbrooke s media and communications department and to the scientific and medical community via local medical grand rounds, publications in high impact scientific journals and departmental meetings.",,2023,N/A,521757.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25288,COV-LT2-0041,The immunologic and virologic determinants of long COVID,"Coronavirus infection has been confirmed in over 157 million people worldwide and over 4 million people in the UK. Initially, there was understandable focus on the care of patients hospitalized with severe disease, but it has subsequently been recognized that many individuals managed their symptoms in the community during the acute phase of COVID-19. The long-term effects of infection in both groups are now becoming apparent. Long COVID describes a broad range of symptoms that persist 12 weeks after acute infection with SARS-CoV-2. Symptoms are diverse and commonly include fatigue, breathlessness, cognitive impairment (""brain fog""), chest pain, palpitations, and persistent disturbances in smell and taste. Data from the Office for National Statistics suggest that over a million people in the suffer with long COVID in the UK. The potential economic impact and anticipated burden faced by the NHS as a consequence of long COVID has been acknowledged more recently, and a spotlight has been focused on the need for research into the multisystem effects of the condition to inform the future development of diagnostics and therapeutic strategies. Published studies have emphasized the importance of immune responses during acute COVID19. However, little is known about the role of the immune system in long COVID. Our study aims to investigate the hypothesis that overactive or maladaptive immune responses drive ongoing systemic inflammation and clinical symptoms in patients with long COVID.",,2024,N/A,1079790.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P25289,COV-LT2-0049,HypErpolarised Xenon Magnetic Resonance PuLmonary Imaging in PAtIeNts with Long-COVID (EXPLAIN),"We wish to understand why some Long-COVID sufferers struggle with breathlessness on exertion and have a reduced ability to exercise. To do this, we will use MRI scanning and a special gas (hyperpolarised xenon) which is breathed in during the scan. The xenon gas is harmless in the quantity we use. This technique shows the movement of xenon within the lungs and moving out of the lungs into the bloodstream, similar to how oxygen is absorbed. The scans take about 15 minutes. In patients hospitalised with COVID-19, we found that scans several months after discharge showed evidence of persisting lung damage, even when other tests were normal. Importantly, on follow-up scanning, some have remained abnormal. We will use the same scan technique in Long-COVID sufferers not admitted to hospital, who have ongoing breathlessness on exertion to see if they have lung damage. If lung abnormalities are found, we will assess their severity and whether they improve over time. To do this, we will compare scans in the different groups of participants enabling us to see if their breathing problems are related to the lung damage. We will also include an MRI scan of the heart in some of the trial participants to see if the heart has also been damaged. If the Xenon MRI scans separate patients with and without lung disease, we will then analyse the CT scans using artificial intelligence and the blood samples to see if we can find associated abnormalities. We aim to provide a much-needed explanation to sufferers of Long-COVID struggling with breathlessness. Learning more about the nature of damage within the lungs through xenon MRI may help with the future development of treatments, and provide a reliable way of measuring lung damage changes over time.",,2024,N/A,2566888.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P25290,CV220-036/1,"COVID-19: Coronavirus STORY (Serum Testing of Representative Youngsters), BAME cohort",Not Available,,2021,N/A,215808.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2021 +P25291,CV220-088 - COMIX,COMIX Extension (Understanding the dynamics and drivers of the COVID-2019 epidemic using real-time outbreak analytics),"CoMix is a unique social contact survey, which has been collecting data on epidemiologically relevant social interactions since March 24 th 2020 [1]. Data are collected by Ipsos-Mori from two panels of 2500 individuals, who are broadly representative of the UK population by age and geographical location. Panel members report on those individuals they had face-to-face contact with (either spoken or physical contact) over the previous day. Each panel reports on alternate weeks allowing weekly information to be collected. The quantitative data gives direct insight of contact patterns in the community (Fig 1), can be used to estimate changes in the reproduction number some weeks ahead of epidemiological data [1], allows the impact of non-pharmaceutical interventions to be inferred [2] and provides key information for accurate parameterisation of mathematical models. Weekly reports from CoMix are shared with key organisations, including SAGE and JBC and are available online [3].",,2021,N/A,1016534.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P25292,NIHR130999,Improving life quality in chronic obstructive pulmonary disease (COPD) by increasing uptake and completion of pulmonary rehabilitation with lay health workers: a cluster randomised controlled trial,"Are trained volunteer lay health workers (LHWs) effective, efficient and acceptable in improving completion rates of NHS pulmonary rehabilitation (PR)? Can the LHW intervention be implemented by PR staff? Background Chronic obstructive pulmonary disease (COPD) is the most common lung disease caused by smoking. It affects more than a million people in the UK. COPD causes breathlessness, cough, and fatigue and exacerbations can lead to admission. PR is the best treatment for the symptoms and impact of COPD. It improves quality of life and exercise capacity. PR classes include exercise and self-management. More than 40,000 COPD patients are referred to PR each year in England, but the benefits are limited by poor uptake. Only 40% of people referred for PR complete it. The reasons why people don'Äôt complete the treatment include travel issues, low mood, uncertainty about its benefits, and shame about smoking. LHWs are at the core of this study. COPD volunteers who have completed PR will be trained as LHWs and will support patients referred for PR. We have shown, in a feasibility study, that LHWs can be recruited and trained to support these patients. LHWs were enthusiastic, committed volunteers, and patients welcomed their support. LHWs are effective in a range of health issues but have been little used in the NHS. Aims and objectives To improve quality of life for people with COPD by increasing by 40% the number of referred patients completing PR with an LHW intervention. To show that the training and management of LHWs can be incorporated into NHS PR services. Type of study Cluster randomised controlled clinical trial of impact of LHW intervention on completion rates in PR centres throughout England. PR centres (clusters) will be randomised to intervention (LHW + usual care) or control arms (usual care). Methods, Work Packages (WP) and Timelines for Delivery WP1. Trial set up - months 1-8: Develop a training package for PR staff to recruit, train and manage LHWs in their PR centres. Refine the LHW training and intervention developed in the feasibility study. Recruit PR centres for the trial. Assess the impact of COVID-19 on PR delivery. WP2. Internal Pilot - months 9-16: Randomise four centres, two to intervention and two to control, to assess PR staff training and LHW intervention delivery. Present outcome of Stop-Go criteria: delivery fidelity; LHW retention; and impact of COVID-19 on trial integrity; to Independent Trial Steering Committee for decision on progression - month 17. WP3. Main trial 'Äì months 18 - 30: Continue trial in a further 34 PR centres, 17 intervention and 17 usual care. Principal outcome will be rate of completion in intervention sites compared to control sites. WP4. Process evaluation: Each element will be evaluated, including PR staff training, LHW training, intervention fidelity, and acceptability to patients, LHWs, and PR staff. WP5. Health economic evaluation. PPI involvement Our COPD advisory group of seven years, with our PPI co-applicant, has been closely involved in the intervention development and will be involved throughout the trial. Anticipated impact and dissemination The LHW intervention will enhance the delivery of PR, improve the efficiency of PR services and reduce waste. The findings will be disseminated through public meetings, a trial website, charitable and professional associations, social media, Youtube video, press releases, and scientific publications.",,2024,N/A,2339405,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health workforce,2021 +P25297,NIHR132807,Remote by Default 2: the 'new normal'?,"BACKGROUND The remote-by-default policy in UK general practice, introduced for infection control during the acute phase of the pandemic, seems likely to be continued long term. There are unanswered questions about how to optimise this service model. AIM To inform a more fit-for-purpose remote-by-default model in general practice which takes account of a) quality and safety of care, b) equity and inclusivity, c) staff wellbeing and training, and d) the wider technical and regulatory infrastructure. RESEARCH QUESTIONS 1. How can we ensure that the remote-by-default model supports high-quality, safe care to all patients (including those at risk of digital exclusion)? 2. How can we balance a remote-by-default model with the provision of traditional face-to-face consultations where appropriate? 3. How can we meet the wellbeing and training needs of general practice staff as remote-by-default becomes business as usual? 4. What are the infrastructural challenges of remote-by-default and how can they be overcome? STUDY DESIGN Mixed-method, multi-site case study with co-design workshops and cross-sector stakeholder events. OBJECTIVES AND BRIEF METHODS 1. PRACTICE LEVEL Objective: Follow a maximum-variety sample of 11 GP practices for 2 years as they seek to introduce, improve and sustain remote-by-default consultations, supporting them in developing effective remote services and equitable alternatives where needed. Methods: Build mixed-methods longitudinal case studies via staff interviews, document analysis, ethnography (adapted to virtual if necessary). Support practices through action research and 2 digital inclusion co-design workshops. 2. PATIENT LEVEL Objective: Capture the patient experience of remote-by-default consultations and ensure this perspective is incorporated in practice- and system-level efforts to improve and augment remote-by-default services. Methods: 40 interviews and 2 digital inclusion co-design workshops with patients and carers. 3. SYSTEM LEVEL Objective: Engage stakeholders 'Äì including policymakers, professional bodies, industry, civil society and patient groups 'Äì in an ongoing dialogue about how to deliver and support a more equitable, less risky remote-by-default service. Methods: 20 elite interviews plus 4 stakeholder events (see below) PATIENT AND PUBLIC INVOLVEMENT (PPI) 'Ä¢ External advisory group with independent lay chair and wide range of lay members bringing cross-sector experience from (e.g.) industry, 3rd sector, arts, policy 'Ä¢ Patient/lay input to study design 'Ä¢ PPI virtual group with buddying of others not fully online 'Ä¢ Innovative approaches to involvement described in main bid KEY DELIVERABLES 'Ä¢ 4 digital inclusion co-design workshops (2 for patients and carers, 2 for GP practice staff) 'Ä¢ Report on diversity of patient experience of remote-by-default, plus digital inclusion personas to feed into other design activities 'Ä¢ 2 years of action research with 10 GP practices to help deliver their priority goals 'Ä¢ Written case studies and cross-case analysis of practices'Äô experiences 'Ä¢ 4 large-scale cross-sector stakeholder events with preparatory and follow-up activities with policy, NHS, industry and patient groups 'Ä¢ Ongoing relationships and implementation action as invited with national-level stakeholders 'Ä¢ Academic papers, policy briefings 'Ä¢ Lay summaries and resources",,2023,N/A,1467311.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,Health Systems Research,Health service delivery,2021 +P25298,NIHR132826,NIHR Global Health Research Unit on Respiratory Health (RESPIRE-2),"The aim of RESPIRE-2 is to deliver low-cost, scalable policy and clinical interventions to reduce respiratory morbidity and mortality across Asia. We will build on capacity development, foundational research and relationships from RESPIRE to catalyse efforts to improve global respiratory health. Our goals include: building research capacity in low- and middle-income countries (LMICs); ensuring research is driven by the needs/priorities of LMIC populations; building equitable/respectful partnerships; engaging stakeholders, including communities, at all stages; and strengthening capacity to translate research findings into impact. We are expanding from RESPIRE work in Bangladesh, India, Malaysia and Pakistan to add 3 additional LMICs - Bhutan, Indonesia and Sri Lanka, focusing on disadvantaged populations; and developing new research themes on TB and key risk factors [tobacco, air quality]. We will adopt the successful management model in RESPIRE - a Unit Management Committee (UMC) - responsible for overall governance, which will be advised by an International Steering Committee. Our 3 research programmes are on Infectious Diseases, Non-Communicable Diseases and Preventable Risk Factors. Our 4 cross-cutting translational platforms address stakeholder and community engagement and involvement; education and capacity building; open science, data and methodologies; and digital health and innovation. These will help promote good research design and practice, support innovation and promote sustainability of the work of RESPIRE-2. We will coordinate their activity and outputs to ensure that new knowledge from RESPIRE-2 results in translational activity and promotes sustainability. Our research programmes are based on our formal priority setting exercises and long-standing collaboration with Asian partners to identify local priorities. We seek to adapt existing or develop new interventions and evaluate these in diverse settings with a focus on vulnerable population, where possible in multi-country studies. Close collaboration with Ministries of Health, study communities and other key stakeholders is a key aspect at all stages of our research cycle. We have worked with patient and community groups to select and design projects. We will work with partners to disseminate new knowledge and effective new approaches widely throughout Asia. We have considered the context of COVID-19 and will collaborate with ISARIC (International Severe Respiratory Infection Consortium) to build capacity in preparedness for emerging respiratory infections. Our research proposals will be subject to external peer review managed by the UMC. These assessments will also offer opportunity for input from technical experts in the platforms to ensure appropriate study design, access to digital health expertise, and data management plan/wider data sharing support - 20 RESPIRE projects deposited data in UK HDR Gateway (BREATHE) and this will continue in RESPIRE-2. In summary, RESPIRE-2 will build on established practices and processes as it works to achieve a step-change in developing applied respiratory research capacity and capability in the context of responding to urgent respiratory priorities affecting the most vulnerable populations across Asia. We remain committed to partnership working with other Units and Groups to maximize the return on these important global health investments. We request an investment of ¬£7M with 60% spent directly in LMIC institutions.",,2026,N/A,8819187.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,,2022 +P25300,NIHR133205,NIHR Global Health Research Group on Diet and Activity -A syndemic approach to the prevention of diet- and physical activity-related NCDs,"RESEARCH QUESTION How can a better understanding of urbanisation and climate-change (syndemic)-related NCD hazards inform the design of resilient built and food environment interventions to support healthy diets and active living in LMIC cities? BACKGROUND The global diet and activity (GDAR) Network addresses the rising NCD burden in low- and middle-income countries and is focused on built and food environment determinants of diet and physical activity (PA). Urbanisation acts in tandem with climate risks to influence diet and PA, especially those living under precarious urban settings at higher risk of climate-change disruptions. We propose a syndemic approach to address built and food environment vulnerabilities due to urbanisation and climate change (syndemic) hazards to equitably and sustainably support and enhance healthy diets and PA. AIM, OBJECTIVES AND METHODS The project aims to inform resilient healthy diet and active living interventions in LMIC cities. Specific objectives are to: 'Ä¢MEASURE SYNDEMIC HAZARD EXPOSURE BY: OBJ 1 Investigating the spatial clustering of a.syndemic hazards and the association with neighbourhood deprivation. b.unhealthy diets and PA and the association with household deprivation. c.Assessing the reliability of virtual assessment tools to measure exposure to syndemic hazards. Methods: Field and virtual audits of built and food environments; spatial analysis of individual, household and neighbourhood data on diet, PA, NCD risk and deprivation from existing cohorts. 'Ä¢ASSESS VULNERABILITY TO SYNDEMIC HAZARDS BY: OBJ 2 Understanding the adaptive capacity of community, policy and commercial institutions to syndemic hazards. Methods: Policy space, corporate political activity and community resilience strategy analyses (reviews, in-depth interviews (IDI), focus group discussions (FGD)). OBJ 3 Evaluating the sensitivity of community and policy initiatives influencing built and food environment responses to the COVID-19 syndemic. Methods: Community initiatives: surveys, FGD, key informant IDI, food environment audit; policy initiatives: policy review (Comprehensive Analysis of Policy on Physical Activity framework). 'Ä¢CO-DESIGN DOUBLE-DUTY BUILT AND FOOD ENVIRONMENT INTERVENTIONS: OBJ 4 Adolescent-focused, syndemic-resilient interventions and policies that promote healthy diets and PA. Methods: PRACTIS guide to identify intervention targets; FGD; intervention prioritisation. TIMELINES FOR DELIVERY Yr1 Collaboration agreements; stakeholder consultation 1; impact indicators; training and leadership needs analysis; research protocols and ethics (Obj 1&2); recruitment; access secondary data, equipment (Obj 1) and policy documents (Obj 2&3), desktop reviews (Obj 2&3); engage collaborators as co-designers. Yr2 Data collection and analysis (Obj 1&2); stakeholder consultation 2; finalise research protocols and ethics approvals (Obj 3&4); design collaborator pilot studies (Nigeria, Brazil, South Asia); data collection (Obj 3&4). Yr3 Data analysis and write up (Obj 1&2); data collection and analysis (Obj 3&4); conduct pilot studies. Yr4 Stakeholder consultation 3; data analysis and write up (Obj 3&4); network evaluation. ANTICIPATED IMPACT AND DISSEMINATION We will build on GDAR'Äôs successful co-production of evidence with partners, adapt methods, embed impact activities, and build Network capacity, informed by recommendations from the Network'Äôs independent evaluation in 202",,2025,N/A,4135785.48,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P25302,NIHR133455,FluCare: Estimating the effectiveness and cost-effectiveness of a complex intervention to increase care home staff influenza vaccination rates,"Background Seasonal influenza (flu) causes thousands of deaths each year in the UK, creating a major risk for care home residents. Whilst the World Health Organisation recommends 75% of social care staff are vaccinated, only 25-40% do so. With a need for tailored interventions, we used the Theoretical Domains Framework (TDF) to create a complex intervention consisting of regular in-care home staff vaccination clinics run by the supplying community pharmacy, free vaccination for all staff, theoretically underpinned information for staff, financial incentives for homes achieving vaccination rates over 70% and regular care home performance monitoring/feedback. Aim To estimate the effectiveness and cost-effectiveness of our complex intervention designed to increase staff flu vaccination rates in care homes for older adults. Method A public and patient involvement advisory group will contribute throughout the project. The project management team, expert advisory panel, trial steering and data management committees will meet regularly, overseeing project delivery. The TDF and Behaviour Change Wheel will underpin individual phases. Phase 1: Intervention finalisation (months 1-2) Intervention components and implementation strategies (e.g. information material production) and trial procedures (e.g. data collection methods, fidelity framework and Mechanisms of Action questionnaire) will be finalised. Phase 2: Feasibility study (months 2-11) 10 purposively selected homes will be allocated to receive the full intervention (2), usual care (2) or different parts of the intervention (3x2) to identify which parts, if any, maximise data quality and minimise bias. Within this we will test and refine methods for collecting outcome data, home/staff/resident characteristics and intervention costs. To understand how organisational context shapes intervention delivery, describe intervention fidelity and acceptability and identify sources of contamination between arms, we will use questionnaires, ethnographic visits, up to 40 interviews and documentary review. Phase 3: Definitive trial (months 8-28) 70 recruited homes and pharmacies will be randomised to intervention or control. This will provide 90% power at a 5% significance level for detecting an increase in staff vaccination rate from 55% to 75%. A process evaluation will be undertaken to assess intervention fidelity; control arm contamination, any reactivity bias; to enable us to explain trial results and generate recommendations for wide-scale implementation. A cost-consequences analysis comparing costs and outcomes across trial arms for different stakeholders (e.g. care homes, NHS and staff) will be undertaken. The cost per percentage point increase in vaccination rate will be estimated. Phase 4: Policy development for dissemination (months 24-32) The TDF and Behaviour Change Wheel will inform our dissemination strategy. We will conduct three stakeholder workshops to identify how to deliver wide-scale intervention implementation in homes. Our policy group will develop and disseminate implementation guidance. Impact Higher care home staff flu vaccination rates and improved resident health.",,2024,N/A,2000060.92,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Orthomyxoviridae,Other,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2021 +P25305,NIHR134801,NIHR Global Health Research Unit on Social and Environmental Determinants of Health Inequalities,"Brazil and Ecuador manifest stark inequalities, including inequalities in health. These inequalities arise from the social determinants of health 'Äì the conditions in which people are born, grow, work, live, age and die. Many environmental factors, including urbanisation and the climate emergency, are increasing priorities for individual and population health. These tend to have the most harmful impacts on the most deprived in society. The health system needs to respond to such social and environmental threats, but its organisation may mean that it is not protecting the most vulnerable in society. To try to reduce the impact of social conditions such as poverty, governments have introduced policies such as conditional cash transfers or housing programmes for the very poor. Similarly, governments may introduce environmental policies to protect the environment and mitigate any harmful effects on living conditions. While such policies may not be primarily aimed at improving health, they may still have large impacts on health and health inequalities, with much of the historical improvement in life expectancy attributable to them. Our Unit will focus on discovering which policies impact health, whether they had a bigger impact on disadvantaged groups (defined by axes such as income, ethnicity, race, sex, geography, migration, urbanicity and deprivation), and how the organisation and provision of the health system (particularly regarding coverage, access and quality) could optimise any positive health impacts. We will build on our existing GHR Group on Social Policy and Health Inequalities and the experiences and relationships that have been moulded by that Group. Over the next five years, we plan to be global leaders, focused on Latin America, in harnessing existing databases by integrating them to evaluate the impact of social and environmental policies on health and health inequalities, and the extent to which these can be affected by the health system. We will develop research capacity in data linkage and policy evaluation as a legacy for Brazil and Ecuador. We will achieve this by: 1. Building and developing high quality data resources in Brazil and Ecuador; 2. Conducting rigorous evaluations of the impacts of social and environmental policies, and the effects of large-scale population migration, on health and health inequalities; 3. Updating or creating small area deprivation indices for Brazil and Ecuador; 4. Determining how health systems are best organised to improve health for all social groups and interact with social and environmental policies; 5. Focusing on priority health outcomes with relevance to Brazil, Ecuador and Latin America, in which the research team have expertise: non-communicable diseases including mental health and asthma; maternal and child health; reproductive and sexual health; COVID-19 and emerging health threats; infectious diseases; and violence; 6. Monitoring progress towards the 2030 Agenda for Sustainable Development (particularly Goal 3, but also any impacting on health equity); 7. Working with stakeholders, communities and the public to develop our research agenda, set priorities, disseminate results targeted to specific audiences and in so doing influence regional and national policy; and 8. Building capacity in the relevant disciplines in global health research in Brazil, Ecuador, the UK and globally through the development of training programmes and the promotion of south-south learning.",,2027,N/A,8819968.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2022 +P25311,NIHR135563,"Eligibility, uptake, safety and effectiveness of COVID-19 therapeutics in real world settings","The UK is experiencing a new wave of COVID-19 infections with the Omicron variant at the same time as high circulating levels of DELTA. There is evidence that the Omicron variant is more transmissible and concerns that existing therapeutics (e.g. COVID-19 Vaccines) may be less effective and other therapeutics, such as monoclonal antibodies (MABs) may become ineffective due to mutations. Novel MABs are limited resources and need to be targeted to those at highest risk of poor COVID-19 outcomes who are most likely to benefit. Interim guidance has been produced for MABs and there is an urgent need to determine the numbers/proportion of the population likely to be eligible for these treatments based on existing guidance to inform planning/ordering. It is also necessary to determine the uptake of treatments as they start to be used to ensure they are being used in line with guidance. We also need rapid real-world evidence of the likely effectiveness of treatments alone and in combination and to identify those patients who remain at risk despite treatments This proposal will address a number of key questions, using existing research ready datasets. The overall aim is to determine the uptake, safety and effectiveness of monoclonal antibodies and antivirals in the community. These questions can be addressed very quickly using the QResearch TRE linked datasets with additional questions answered according to DHSC priorities.",,2022,N/A,295076.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Data Management and Data Sharing | Innovation,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Therapeutics logistics and supply chains and distribution strategies | Adverse events associated with therapeutic administration",2022 +P25312,NIHR135575,Rapid Outcomes of COVid therapeutics in Eave II (ROCOVE),"This study is investigating the uptake, safety, and effectiveness of mAb therapy for COVID-19. In January 2022, the UK is experiencing a new wave of COVID-19 infections with the Omicron variant, at the same time as high circulating levels of Delta. There is evidence that the Omicron variant is more transmissible and concerns that existing interventions (e.g., COVID-19 Vaccines) may be less effective and some monoclonal antibodies (mAbs) may become ineffective due to mutations. Novel mAbs are limited resources and need to be targeted to those at highest risk of poor COVID-19 outcomes who are most likely to benefit. Interim guidance has been produced for use of novel mAbs and there is an urgent need to determine those likely to be eligible for these treatments to inform planning/ordering. It is also necessary to determine uptake to ensure they are being used in line with guidance. Rapid real-world evidence is also needed of the likely effectiveness of treatments alone and in combination to identify those patients who remain at risk despite treatments. This research will address a number of key questions, using existing research-ready datasets. We will use a data platform containing pseudonymised, linked data from vaccination records, virological testing and sequencing, clinical, and mortality records with coverage for the whole Scottish population. All data and analyses will be hosted within Public Health Scotland (PHS) and in due course in the Scottish national Trusted Research Environment.",,2022,N/A,153332.91,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Adverse events associated with therapeutic administration",2022 +P25314,NIHR151601,Glucocorticoids in Adults With Acute Respiratory Distress Syndrome: Randomised Clinical Trial (GuARDS Trial),"Research question: What is the clinical and cost effectiveness of dexamethasone given early (within 72 hours of diagnosis) in acute respiratory distress syndrome (ARDS)? Design: Multi-centre, parallel group, allocation concealed, open label, pragmatic, group sequential design randomised controlled trial, with internal pilot Setting: Approximately 60 UK intensive care units (ICUs) Target population: Adult ICU patients with moderate-to-severe ARDS Inclusion criteria: --Aged >=16 years --Moderate or severe ARDS, as defined by the Berlin Consensus criteria for ARDS. Briefly this includes a)ARDS within 1 week of a known clinical insult and b)bilateral opacities on chest imaging and c)respiratory failure not fully explained by cardiac failure or fluid overload and d)Hypoxaemia defined as PaO2/FiO2 ratio <26.6 kPa with PEEP =5 cm water. -Within 72 hours of meeting ARDS criteria Exclusion criteria: -ARDS due to confirmed SARS-Co-V2 infection (COVID-19 ARDS) -Major upper gastrointestinal bleeding during current hospital admission, defined as requiring endoscopy and transfusion for two or more units of packed red blood cells -Glucocorticoids are required for a proven clinical indication (note: stress dose steroids required for septic shock will not be excluded) -Hypersensitivity to dexamethasone -Treatment withdrawal imminent within 24 hours -Previous enrolment in the trial Health technologies being assessed: Intravenous dexamethasone 20mg OD day 1 to day 5, reduced to 10 mg OD day 6 to day 10. Measurement of costs and outcomes Primary: All-cause mortality 60 days post-randomisation Secondary: -In hospital: Successful extubation; Duration of mechanical ventilation; ICU, and hospital length of stay; Health-related quality of life (HRQOL) and adverse events. -At 90-days: HRQoL; Mortality -At 180-days: Reintubation; Mortality; HRQoL; Health service use Health economic evaluation: Cost-effectiveness from NHS and personal social services perspective as per NICE reference case specifications. Follow up: Up to 180 days post-randomisation. Sample size: 854 per group (1708 in total). Timeline:Start date is 01-03-2023. Prior to start date and in conjunction with PPI, we will draft the protocol, and site training materials. We expect a lead time of 6 months to secure ethical and regulatory approvals. We plan to set up 5-10 sites/month, and recruit the first patient in month 7. We estimate duration of recruitment to achieve a sample size of 1708 will be 42 months (at 0.8 participants/site/month). We will undertake an internal pilot for the first 9 months of recruitment, to set-up all 60 sites and recruit 268 patients. Participants will be followed-up for 6 months and further 6-months for close-down, data-cleaning, analysis and reporting. The total study duration is 60 months. Expertise: Our multi-professional team includes clinical trialists, leaders in critical care, pharmacists, methodologists, statistician, health economist, and family representatives, to optimise all aspects of trial delivery. Anticipated impact and dissemination: The results of this definitive trial will establish best clinical care where there is uncertainty, and will determine best value for services. Dissemination will take multiple routes including publication in international, high impact factor, journals, presentation at relevant national and international conferences, and communication with involved participant and family networks including social media and lay press.",,2028,N/A,2755438.89,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2023 +P25318,NIHR154310,Shaping care home COVID- testing policy: A pragmatic cluster randomised controlled trial of asymptomatic testing compared to standard care in care home staff (VIVALDI-CT),"BACKGROUND: Regular asymptomatic testing of care home staff enables earlier outbreak detection protecting vulnerable residents from COVID-19 infection, but is known to have unintended negative consequences. Currently, there is a lack of evidence concerning: the relative benefits/harms of testing; the best approach to ensure compliance with testing; how to sustain testing over time; the parameters in which ongoing testing is warranted; or the nature of unintended and negative consequences. Interdisciplinary and multi-method research, including a rigorous trial, is urgently required to resolve these questions, inform policy, and direct service delivery. PROJECT AIM: The project examines the relative benefits and harms of regular COVID testing targeting asymptomatic staff in UK care homes. METHODS: The project is delivered by an experienced, inter-disciplinary team between November 2022 and April 2024. It capitalises on existing data infrastructure and partnerships with providers. Work-package 1 'Äì Intervention development: using published literature, stakeholder input, and theory, we will coproduce a sustainable, multi-component testing intervention for staff using Lateral Flow Devices, considering: 1) staff sickness payments; 2) psychological strategies to improve testing compliance; 3) testing frequency. Work-package 2 - Pragmatic cluster randomised trial: we will evaluate the effectiveness of the testing intervention versus testing policy in place nationally at the time of the trial in 140 control and 140 intervention homes. Primary outcome: number of unplanned hospital admissions in residents. Key secondary outcomes: mortality, testing uptake, outbreaks, prevalence of COVID-19 among tested staff. Work-package 3 - Process evaluation of intervention and control: qualitative interviews with staff, families and visitors in 28 homes to establish the acceptability, feasibility and impact of the testing intervention, and refine programme theory detailing how the intervention works, to inform its future roll out if successful. Separately we will assess the impact of testing and COVID-19 outbreaks on social care related quality of life in 3 intervention and 3 control homes using the Adult Social Care Outcomes Tool. Work-package 4 - Economic analysis: using routine NHS datasets and provider administrative records we will itemise the costs and benefits of the testing intervention versus standard care from a NHS, personal social services and societal perspective. We will model COVID-19 transmission in residents and staff to estimate the number of COVID-19 infections and deaths averted by the testing intervention and estimate its cost effectiveness under different epidemiological scenarios. Work-package 5 - Stakeholder engagement: We will hold 4 roundtable discussions for key stakeholders to engage them in the study, and co-develop plans for dissemination and implementation. PUBLIC AND PATIENT ENGAGEMENT: Public advisors will be involved at all stages of the trial. IMPACT AND DISSEMINATION: Findings will inform testing policy and winter planning and longer-term strategies to prevent respiratory infections in care homes. We will disseminate results using traditional and non-traditional media, an in-person conference, virtual knowledge exchange events and by visiting care homes.",,2024,N/A,1241500.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Social Workers | Caregivers,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Policies for public health, disease control & community resilience","Diagnostics | Impact/ effectiveness of control measures | Supportive care, processes of care and management | IPC in health care settings | Approaches to public health interventions | Policy research and interventions",2022 +P25324,NIHR201483,"Impact of feedback from Real-time, electronic symptom monitoring on post-discharge recOvery after Surgery for oEsophago-gastric cancer: a multi-centre randomised controlled trial (the ROSE study)","Aim To find out if patients recovering at home from surgery for oesophago-gastric (food pipe or stomach) cancer benefit from feedback from electronic (web-based) reporting and monitoring of their symptoms. Background Around 13,500 people in England and Wales are diagnosed with oesophago-gastric cancer each year, of which around 5,000 (40%) have major surgery. Patients stay in hospital for around 1-2 weeks after surgery. Even when well enough to continue their recovery at home, patients may still experience surgery-related problems or feel unwell with symptoms such as pain or tiredness. There is growing evidence from patients undergoing other treatments (such as chemotherapy) that electronic (web-based) reporting of symptoms can improve patients wellbeing because it provides a way to provide patients and their healthcare team with feedback about how best to manage symptoms. However, this has not been studied in patients undergoing surgery for cancer. Design and methods We will invite 206 patients having surgery for oesophago-gastric cancer at six NHS hospitals in England to take part. Patients will be randomly placed in one of two groups. Patients in the web-based monitoring and feedback group will be asked to report their symptoms using the web-based system while continuing to receive their usual clinical care. Depending on the seriousness of reported symptoms, the system will immediately provide feedback about self-care, advise them to contact their healthcare team, or send an automatic alert to their healthcare team. Patients in the usual care group will receive their usual clinical care but will not use the web-based system to report symptoms or receive feedback. Patients will complete questionnaires during the study, including before their surgery, when ready for discharge home and at several timepoints up to four weeks after going home from hospital. We will use the questionnaire answers to see if patients in the web-based monitoring and feedback group have a better recovery from their surgery than those in the usual care group. We will also look at whether the web-based system is good value for money for the NHS. Patient and public involvement We have worked closely with patients and members of the public to develop the study and draft this application, including choosing the questionnaires and deciding how many times patients will complete them. We will continue to work with patients and members of the public during the study, for example asking them what information should be included on participant study information leaflets. Communicating study findings We will share our study findings with the NHS and by publishing in scientific journals and presenting at scientific meetings. We will work with patient groups and professional organisations to make sure our findings are shared widely and explained in ways that everyone can understand.",,2025,N/A,426061.82,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Other,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25329,NIHR203292,"A single-blind, randomised, phase II UK multi-centre study to determine reactogenicity and immunogenicity of booster vaccination against ancestral and novel variants of SARS-CoV-2 (COV-BOOST)","As of April 8th 2021 the MHRA in the UK has granted Regulation 174 approval for emergency use of 3 vaccines for protection against COVID-19 in the UK, including the mRNA vaccines BNT162b2 (Pfizer) the mRNA-1273 (Moderna) vaccine, and the chimpanzee adenovirus vector vaccine ChAdOx1-nCov19 (AstraZeneca/Oxford). So far over 30 million people in the UK have received at least one dose of either BNT162b2 or ChAdOx1-nCov19, with supplies of the mRNA-1273 expected imminently. Annual or seasonal booster vaccination for high risk groups is thought likely to be required, especially in light of the emergence of new variants of the SARS-CoV-2 virus. There is concern from studies in South Africa and elsewhere that existing vaccines may be less effective against these variant strains. It is currently unclear which booster vaccine schedule will provide the best safety profile and immune responses, according to which vaccine was originally given. The Joint Committee for Vaccination and Immunisation and UK Chief Medical Officers need timely information regarding the effects of different booster vaccinations on the safety profile and immunity to previous and new variants of SARS-CoV-2 in order to inform national policy for autumn and winter 2021. This study will determine the immune responses provided from different booster vaccinations given a minimum of 3 months from the 2nd dose of an initial course of AstraZeneca/Oxford or Pfizer vaccines.",,2024,N/A,45962222.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Phase 2 clinical trial | Characterisation of vaccine-induced immunity,2021 +P25333,NIHR203566,Evaluating a brief novel treatment for COVID-related Post-Traumatic Stress Disorder (PTSD) in the Health and Social Care workforce: a pre-RCT preparatory study,"Background High levels of Post-Traumatic Stress Disorder (PTSD) are reported in frontline health and social care workers (HSCW) who have worked through the pandemic. These levels of PTSD are comparable to those in military veterans who have been involved in warfare. Staff with PTSD present a patient safety risk due to high staff absences and mistakes. Currently the best treatment available for PTSD is lengthy, costly and 30% of people undertaking this treatment drop out before the end. New PTSD treatments are therefore needed. In an ongoing study we are looking at one new treatment called Reconsolidation of Traumatic Memories (RTM) in 60 military veterans with PTSD. RTM treatment is much shorter, and therapists can be quickly trained. In our review of research that has taken place, six small studies show that it looks promising in removing symptoms of PTSD 12 months later. Aims Our study aims to develop an RTM treatment route for health and social care workers with PTSD and to develop an understanding of what their employers consider to be important health benefits for their staff. Before we can proceed with the study in the NHS we need to understand three things better: 1) Do staff want to receive treatment and participate in research and how? 2) Can RTM training undertaken by veteran-charity therapists also be successfully taught to psychological therapists employed by the NHS? 3) What employer benefits are important to measure e.g. sickness-absence rates and/or mistakes made by staff while working. Design & Methods The main purpose of the study will be to develop a funding application to undertake further research of RTM to determine whether it works, how it works and is it safe compared to similar treatment. We propose a 3-phase study. Phase 1 will recruit 24 individuals made up of NHS and social care workers and families, NHS occupational health/staff health support managers, senior managers and members of the public to meet in groups to discuss and answer the research questions. Staff PTSD treatment routes within the NHS will be developed. Phase 2 will train and assess four psychological therapists in delivering RTM. Phase 3 will deliver RTM to twelve health and social care workers with PTSD to see if they will start therapy and take part as research participants. Patient and Public Involvement Three frontline staff, two public contributors and seven other stakeholders informed the research design, the lay summary and will support the funded study. Research outputs The results, together with those of the veteran trial and our review of previous research, will support a funding application in late 2022 to test whether RTM can be proven to be a successful treatment within the NHS.",,2024,N/A,168727.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers | Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19 | Other,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health workforce",2022 +P25337,NIHR204237,Evaluation of the Multi-Agency Child Safeguarding Reforms,"Background Child safeguarding is about keeping children safe from harm so that they can have the best outcomes in life. Safeguarding needs all people working with children to work well together. This can be difficult because there are so many different organisations involved and because family circumstances vary so much. Through recent reforms, the government has brought together the Local Authority, Health and the Police in Local Safeguarding Children Partnerships (LSCPs) and given them joint responsibility for safeguarding. However, we do not know how well LSCPs are doing, and it is difficult to measure the impact because of differences between local arrangements, and also because the COVID-19 pandemic increased risks for children and young people and led to changed ways of working. Aims In this project we will provide evidence about what makes LSCPs effective. We will focus on how well joint working happens and how oversight arrangements may improve outcomes for children in different local circumstances. We will take into account the impact of the pandemic. We will explore effective ways of making sure that LSCPs hear and adapt to the?views and experiences of children, young people and families. We will recommend ways to check how well the reforms are working and whether the safeguarding system is improving children s outcomes over time in local areas and nationally. The project is led by experienced academics from King s College London and the University of Bedfordshire in partnership with The Association of Safeguarding Partners and Camden Safeguarding Children Partnership Young Advisors and in collaboration with The Association of Child Protection Professionals and Family Rights Group. Methods The project lasts for two years with three key stages. In Stage 1, we will send an online survey to LSCPs. From the results we will work out what might explain effective multi-agency working in different areas and suggest some outcomes we could measure to check progress. In the second stage, we will select local case study areas where we will run workshops to test our ideas. We will explore with professionals, parents and carers, and children and young people how different circumstances and arrangements in different local areas influence what works best and how COVID-19 has affected how well the reforms have worked. In the final stage, we will develop a tool to capture local and national progress on improving outcomes for children and young people in the future. To be successful, the tool must reflect what outcomes are important to children, young people and families as well as professionals and the government, and must be easy to use and interpret. Therefore, we will provide progress reports and invite discussion and feedback throughout the project, using a variety of formats to communicate with different audiences.",,2024,N/A,599949.97,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Other secondary impacts,2023 +P25338,NIHR204264,Care Home Activity Providers facilitating Public Involvement in research as meaningful activity for care home residents (CHAPPI),"We want to understand how care home activity providers and researchers could work with care home residents to enable them to become involved in research as members of the public and have their voices heard. Background People with ""lived experience"" can influence research, making it more meaningful and relevant. Public involvement in care home research has typically included older people living in the community or family carers, but residents themselves are rarely involved. COVID-19 stopped our planned public involvement in care homes, as researchers could no longer visit. Perhaps care home activity providers could arrange research public involvement as an activity, as they were part of the staff? We worked with the National Activity Provider Association to try this. Activity providers ran public involvement activities about our research with their residents. Activity providers fed back to the research team, and resident insights informed our research. We now want to learn more about this method of public involvement. Methods To research public involvement, genuine involvement opportunities are needed for residents. This project will use three studies we are involved in. Our research will observe and ask people (in interviews) about the public involvement to understand if the involvement is possible, enjoyable and influences the research activity and findings. Different activities will be used by activity providers to enable care home residents to be understood and give their views on the research, depending on resident preference and cognitive ability. Activities will use written words, pictures, videos and games that will explain the studies to care home residents, and help them to use their experience to influence the research (e.g. which questions are important, how to recruit residents). We will explore the process of setting up the public involvement activities, including resources needed and costs. We will observe the public involvement process. We will interview care home activity providers, residents, relatives, care home staff and researchers, asking their experiences and views about the public involvement process. Public involvement The project is based on ideas suggested by a family carer and a care home manager, responding to restrictions on visiting care homes during COVID-19. Our Public Involvement group (including care home residents), will be offered choice in how they want to be involved, including decision making, developing study materials, providing perspectives on findings, and planning dissemination activities. All Public Involvement members will be offered payment according to NIHR guidance and will receive feedback on their input. Dissemination Our findings will inform co-produced How to guidance about activity providers facilitating resident involvement, to be shared widely and used by activity providers and researchers. The research will engage residents in meaningful activity, reducing social isolation, and support professional development of activity providers.",,2024,N/A,279498.48,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2023 +P25339,NIHR204667,MEMVIE 4,"Vaccines are an effective tool against infectious diseases. All decisions on changes to vaccination programmes or the start of a new programme must be driven by the best evidence available. Predictive mathematical models and health economic evaluations have a vital role to play in underpinning the advice from JCVI (the Joint Committee on Vaccination and Immunisation) - the committee that advises on national vaccination policy. Modelling the changes in disease and the health-economic consequences, allows JCVI to assess the cost-effectiveness of any change to the vaccination programme. Our research has been instrumental in providing independent predictions to JCVI for the last nine years, enabling this committee to deliver appropriate and timely advice. Given the international prominence of the JCVI, this advice often influences worldwide policy. This project will build on our expertise in four key domains (epidemiological modelling, health economics, public health and public/patient involvement), and our experience of generating the required predictions. These predictions are based on the results of carefully designed mathematical models using the latest understanding of a particular infection, fitting to the available data on cases and vaccine performance, and taking into account groups that may have a higher burden of infection and disease. These projections are then interpreted in a health-economic framework, carefully considering the costs and benefits (both in terms of health and cost impacts) of any change to vaccine policy. This work will be supported by our ground-breaking public involvement using the framework we have developed to guide how public contributors can inform modelling. We will extend the diversity of our already existing public reference group to ensure a range of voices are represented. The precise work-plan will evolve through careful and regular discussion with the three key stakeholders: DHSC (Department of Health and Social Care), JCVI and UKHSA (UK Health Security Agency - who also perform similar modelling and health-economic studies). Together we will determine the forthcoming changes in vaccine programmes, and the new vaccines that could be deployed in the near future, that need our modelling input. We will also be responsive to emergency planning, providing rapid predictions and forecasts to emerging outbreaks worldwide, as we did for the COVID-19 outbreak. The project places considerable emphasis on sharing information. Regular reports on progress will be presented to all stakeholders, to capitalise on their expertise and to ensure all aspects of the problem are fully explored. Our work will be published in peer-reviewed journals and code released to both increase the reach of the research and as an extra level of validation. Finally, we are committed to a programme of public outreach, ensuring the public is well informed about the scientific bases of potential future changes.",,2026,N/A,1142927.42,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Policy research and interventions,2023 +P25341,NIHR205384,The PHARM-LC Study: What role can community PHARMacy play in the support of people with Long Covid?,"Background to the research Long Covid, persistent symptoms after acute COVID-19 infection, is common and can have serious consequences. About 2 million people in the UK have Long Covid. Symptoms include: extreme fatigue, shortness of breath, aches and pains and difficulties concentrating (""brain fog""). Women, social care workers, people with additional health conditions, and people living in more deprived areas are at higher risk of developing Long Covid. Primary care plays a key role in supporting people with Long Covid. This includes community pharmacy, which can support people who may not seek help from their GP or have difficulty in seeing their GP. There are over 11,700 community pharmacies in the UK. These are often conveniently located and can be accessed without appointment. Community pharmacies could provide support for Long Covid but further research is needed to understand how. Aim of our research We will explore experiences of people with Long Covid to understand how they manage their symptoms and who they seek help from. We will explore the views of staff working in community pharmacies (pharmacists, dispensers, counter assistants) to understand their role in providing support for Long Covid. We will use findings to develop an online training module for community pharmacy staff. Research methods We will interview 20 people with Long Covid and 20 community pharmacy staff. Interviewees will be identified through professional groups and social media. Interview data will be analysed to find common experiences and themes. We will work with pharmacy educators, healthcare professionals, pharmacists, and members of the public to design new online training for community pharmacy staff. Training will help community pharmacy staff support people with Long Covid. Sharing our findings We will share our findings in several ways and in plain English where suitable: Training module made available through CPPE (Centre for Pharmacy Practice Education - which has access to a network of 65,000 pharmacy staff) YouTube video to raise awareness about the role of community pharmacists in supporting people with Long Covid. Articles for magazines, and interviews with local media (press/TV/radio). Articles for professional practice journals. Academic papers and conference presentations. All resources will be shared through professional networks, social media and our collaborators, including Long Covid patient groups (e.g. https://www.longcovid.org) Patient and public involvement Two public co-applicants (Jones and Briggs) with lived experience of Long Covid have been actively involved in helping to develop the study. Further support has been provided by members of Long Covid Support and Greater Manchester Long Covid peer support groups. A public/patient advisory group of 6-8 people with lived experience of Long Covid from diverse backgrounds will be set-up. This group will provide patient/public views on the research and development of online training module.",,2025,N/A,190491.11,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Post acute and long term health consequences | Policy research and interventions",2024 +P25344,NIHR301520,"Measurement of the Aerosol Generating Potential of Intubation, Extubation and associated airway procedures 'Äì MAGPIE study","Aims of the Research Measure the amount of particles (aerosol) released into the air during medical procedures Measure how long particles (aerosol) remain in the air following medical procedures Develop ways to reduce the amount of particles (aerosol) released into the air during medical procedures Background The COVID-19 pandemic has had a huge effect on global health and the world economy. Coronavirus spread during hospital procedures is a big concern. Safe delivery of essential NHS services is affected by the need to reduce coronavirus spread to staff and patients. Aerosols can be created during medical procedures and occur when tiny particles are suspended in the air. Aerosols can carry viruses, like the coronavirus. These aerosols may cause infection by allowing hospital staff or patients to breathe coronavirus into their lungs. Many operations need a general anaesthetic, where a patient is not awake for surgery. A breathing tube is placed to allow surgery to be performed. Insertion and removal of the breathing tube may produce an aerosol which risks spreading coronavirus to staff in the operating theatre. This risk means all staff present must wear enhanced personal protective equipment (PPE) such as 'respirator-type' face masks. It is unknown how much aerosol is produced for many procedures and how long aerosols remain in the air. The use of enhanced PPE: Is expensive for the NHS Increases the risk of medical mistakes Reduces staff and patient contact Makes talking and hearing more difficult for healthcare workers and patients Increases stress and anxiety for healthcare workers and patients Is uncomfortable Makes teamworking more difficult Produces lots of non-recyclable waste The amount of PPE is limited. PPE needs to be used where it is most needed. At the moment, staff wear enhanced PPE for every patient having an operation to reduce coronavirus spread. Staff and patients are not allowed to move in or out of a room for 10 minutes at the start and end of surgery because of the risk from aerosols. This increases the time taken for every operation and has almost halved the number of patients having an operation each day. This includes operations for life-threatening conditions like cancer. Design and Methods This research will be performed with an experienced team of aerosol specialists and airway doctors. Workstream 1: Using highly accurate scientific equipment I will measure the amount of aerosol produced during medical procedures to help patients breathe. These procedures include insertion and removal of breathing tubes for patients having a surgical operation, and facemasks used on intensive care. Workstream 2: I will perform a national survey of medical staff at risk of viral infections from aerosols. The aim is to find out barriers that may prevent new guidelines being used. Workstream 3: I will produce methods to reduce aerosols when a breathing tube is inserted or removed Patient and Public Involvement I undertook a survey of local anaesthetists. The survey showed aerosols were their biggest concern for catching coronavirus. It also showed enhanced PPE increased stress and anxiety, increased the risk of mistakes and caused operations to take longer. Input from a patient representative in a local hospital was supportive: 'Having read your proposal the benefits that would be created are clear. The loss or reduction of staff/patient contact is key in my view, certainly in terms of reassurance and also clear understanding of procedures taking place.' Dissemination The results will be shared with: Participants Government policy makers The Royal College of Anaesthetists and Intensive Care Society Journals/conferences Twitter The results will help produce regulations for safe NHS working, improve NHS efficiency, reduce non-recyclable waste and save the NHS money.",,2024,N/A,551268.6,Human Populations | Viruses | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Hospital personnel,Non-Clinical,Not applicable,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2021 +P25347,NIHR302405,INTEGRATE: Using routinely-collected healthcare data to inform clinical guidance and improve population health,"Background The National Institute for Health and Care Excellence (NICE) is a global leader in developing guidelines for clinical care. However, there are areas of important need where treatment recommendations cannot be made due to lack of robust evidence to inform them (what should we do?). In the UK we are fortunate to have a wealth of routinely-collected healthcare data that is used by approved researchers in a safe and anonymised manner. It can be used to study important health questions such as the effects and safety of prescribed drugs, which may be particularly important when there is little evidence from randomised trials. However, at present routine healthcare data is little used to develop guidelines about the effects of drugs as there is concern that the results are less robust than that from randomised trials. However, there could be benefits to using this data: it is immediately available, low cost to analyse, and provides evidence about drug effects in the whole population rather than those included in trials. In addition, at present NICE do not monitor the uptake and effects of their guidelines (does what we do work?). Not assessing use of guidelines by healthcare workers means that we cannot understand or improve differences in uptake between men and women, among different ethnic groups, people with different income levels and between regions of England. This could lead to reduced health benefits and higher healthcare costs (how can we do better?). Aims and objectives The aim of the INTEGRATE study is to work in partnership with NICE to address these questions by identifying whether evidence from routinely-collected healthcare data can inform and increase the impact of clinical guidance produced by NICE. The objectives are to: Create early robust evidence where randomised trials are lacking. Assess the extent of implementation of guidance and variations in care. Determine the health and economic impact of implementation or non-uptake. Methods Workstream A: Using routinely-collected data to inform guideline development In this workstream we will jointly plan a series of three research studies. I will then analyse each using a scientific approach that treats the data as if it was a clinical trial. At the end of each study we will review what has been learnt to help improve the methods for the next one. By the end of the project we will jointly develop a framework to help NICE decide when routinely-collected data is helpful to address uncertainty in the future. Workstream B: Using routinely-collected data to assess and evaluate guideline impact Having jointly decided on a recent NICE guideline to study I will use routine healthcare data to identify what proportion of patients who should receive a drug are being offered it, looking in detail at whether this varies by sex, ethnicity, income and region. These results will feed into efforts to improve uptake of guidance in areas of need. I will then go on to study whether the guideline has led to improved health and to lower healthcare costs. Patient and Public Involvement Through our current research programme, we have developed a diverse and inclusive online patient and public advisory group. We will seek volunteers from this group to join the INTEGRATE steering group to help with all stages of the project including development of future research questions, interpretation of findings, providing feedback on plain English summaries and other methods of dissemination. Dissemination The impact of the INTEGRATE project will be to improve how NICE use evidence from routine data to develop and implement guidelines, strengthening their work into the future and with potential cost-efficiencies and benefits for the health of the population.",,2027,N/A,2208348.84,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health information systems | Health leadership and governance,2022 +P25351,NIHR302934,Informing interventions to support children and young people with long-term effects of infections in the SARS-CoV-2 pandemic era: Analyses of linked survey data and electronic health record data in England,"Background SARS-CoV-2 infection (which causes COVID-19 disease) is generally mild in children and young people. However, a large number have symptoms weeks after infection, loosely termed 'long-COVID'. Previous studies, and an online discussion group with families affected by long-COVID held to inform this study, have shown that symptoms are wide-ranging and can be severe. The National Institute for Health and Care Excellence considers long-COVID to include the broadly-defined 'ongoing symptomatic COVID-19' (signs and symptoms 4-12 weeks after infection) and 'post-COVID-19 syndrome' (signs and symptoms more than 12 weeks after infection), but does not specify what these symptoms are. The likelihood of children and young people developing long-COVID, which of them are most at risk, and their long-term outlook, are unknown. Many different viral and bacterial infections besides SARS-CoV-2 can cause lingering health effects in children and young people. It is not clear if the reasons for developing long-term health effects from other infections are similar or different to long-COVID. It is also not known whether the healthcare needs are similar or different. Consequently, the burden on the NHS and wider society is unknown. All of these gaps in our knowledge make it very difficult to plan healthcare services, and for doctors to advise at-risk and affected children and young people. The Schools Infection Survey The Schools Infection Survey (SIS) is the only nationwide study of SARS-CoV-2 infection in schoolchildren (4-18-year-olds) in England. During the academic years 2020-21 (SIS-1) and 2021-22 (SIS-2) it regularly tested for SARS-CoV-2 infection and recorded symptoms and school absence for all participants. The Department for Education also has data on school absence. SIS-2 recently reported that 1.8% of primary school pupils and 4.8% of secondary school pupils had long-COVID. Linking to data on numbers of GP visits, hospital admissions, related diagnoses, and prescriptions following an infection in SIS participants could give us a lot of information about how SARS-CoV-2 and other infections affect children and young people, as well as the burden and cost to the NHS. Using linked data would avoid using more questionnaires, which the discussion group said can be burdensome for families with an ill child. Factors which contribute to vulnerability to long-term health effects, such as age, gender, deprivation, pre-existing illnesses, and multiple infections, will be investigated. Research Questions and Methods This research will address the following questions: 1. How many children and young people in England have long-COVID, what are their risk factors, what are their healthcare/educational needs, and what is the associated cost? 2. How similar or different are the risk factors, healthcare/educational needs and cost, and numbers affected, for long-term effects of other infections (using fever as a marker) in children and young people in England? To do this, SIS data will be linked to data on health service attendances, diagnoses, prescriptions, and school absence. Different infectious causes of fever will be investigated. The results from SIS will be scaled up for all children in England. Use of Study Findings This four-year study begins in April 2023. Within the first 18 months, the risk of long-term outcomes will have been analysed, and initial cost estimates produced. The findings will be published in academic journals and policy reports, and shared with the media. Information will be produced to provide much-needed reassurance for affected families, and to empower families to decide when to manage symptoms at home and when to seek a healthcare consultation. Families affected by long-COVID will be engaged regularly throughout the study, and will be crucial to shaping the study outputs. They have already advised that videos would be more accessible than a lot of written information.",,2027,N/A,870892.8,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Policy research and interventions,2023 +P25354,COV0051,COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR),"The international demand for accurate diagnostics to improve patient health and optimise healthcare resources in the COVID-19 (SARS-CoV-2) pandemic is steadily increasing. In response to the pandemic, the life sciences industry has seen an influx of new in vitro diagnostic tests (IVDs). However, recent evaluations of these diagnostics are mainly single centred, employ differing reference standards with variable protocols which means limited comparability between tests and ultimately a longer time to useful results to guide clinical care. Leveraging our existing infrastructure and collective expertise, we propose to work as a collaborative national platform for COVID-19 diagnostics research and evaluation. To ensure a methodologically robust, standardised approach to the evaluation process and to avoid duplication of effort, we will mobilise a network of hospital laboratories, primary and secondary care settings and care homes. CONDOR will deliver rapid, robust evaluation of medical tests to support diagnosis and management of patients with suspected COVID-19. This collaborative platform will also place the UK in a unique position to rapidly evaluate and adopt novel diagnostics into clinical practice when faced with future pandemics. The platform has 4 elements: 1) A central triage point for novel diagnostics through an expert steering committee 2) Analytical performance evaluation of IVDs (molecular, antigen and antibody tests) via a laboratory network 3) Evaluation of clinical performance (diagnostic accuracy) of IVDs (self-tests, POCTs and laboratory platforms) in established clinical networks 4) Cross cutting workstreams. a. Care pathway analysis for COVID-19 diagnostics b. Evaluating utility and usability in laboratory and clinical settings",,2022,N/A,1766611.88,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P25355,COV0170,HICC: Humoral Immune Correlates for COVID19: Defining protective responses and critical readouts for Clinical Trials of Vaccines and Therapeutics,Not Available,,2022,N/A,1921735.46,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation",Immunity,2020 +P25356,COV-EPI-01,Funding for epidemiological analysis to inform HMG'Äôs COVID-19 response,Not Available,,2021,N/A,263181.76,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Epidemiological studies,,2021 +P25357,COV-LT-0009,"Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services","We will address the following patient defined questions: What is long-COVID and how is it diagnosed? Why have I got long-COVID? What effects will long-COVID have on my health, ability to work and family? What are my chances of recovery? How will this research ensure I am getting the right treatment and support for long-COVID? Physical and mental health consequences of C-19 infection, termed long-COVID, occur frequently. Our understanding of long-COVID, including how best to diagnose, risk factors, health and economic consequences, is poor, limiting efforts to help people. We will use a combination of national anonymised linked primary care electronic health records, and longitudinal studies of people of all ages across the country. We have asked participants about C-19 infections, long-COVID symptoms, and have collected health and socioeconomic information for many years before the pandemic. From these studies, we will ask people reporting long-COVID, and comparator groups, to wear a wrist band measuring exercise ability, breathing, and heart rate, and complete online questionnaires on mental health and cognitive function. They will also be invited to clinic for non-invasive imaging to look at potential damage to vital organs, such as the brain, lungs and heart. Patients, members of the public overseeing electronic health record research, and study members have been involved in shaping the research questions, and will be consulted for the duration of the project. In addition, people with long-COVID and their families, from the studies, will be involved in shaping the diagnostic tools for long-COVID, and aiding our understanding of determinants of recovery, and responses to therapy. We will share findings with bodies involved in guidelines (NICE, who are also part of this project), with government (via the Chief Scientific Advisor), with the public via social media and other outputs, and the scientific community via research publications.",,2025,N/A,13333750.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Policy research and interventions,2021 +P25358,COV-LT-0013,"Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)","Background: Some people who have survived COVID-19 infection develop longer-lasting symptoms, known as Long COVID. Many lack support and are given conflicting advice. Aim: To work out which treatments are most likely to benefit people with particular symptoms and test supportive treatments to improve their quality of life. Design and methods Work package 1 will identify people that had COVID-19 from GP records. Study participants will be invited to use a digital platform to report Long COVID symptoms/quality of life. Work package 2 will assess Long COVID symptoms. Participants with severe symptoms will be contacted by a nurse to provide advice/support. Blood test results and wearable data will help us understand which treatments might be best to support specific groups of Long COVID patients. Work package 3 will review evidence for treatments for Long COVID including drugs or supportive interventions (e.g. for mental health or tiredness). Working with patients, doctors and other experts we will recommend treatments that should be tested in Long COVID patients and develop supportive interventions which can be delivered using the Long COVID platform. Work package 4 will establish a digital trial using the Long COVID platform to test whether supportive interventions can benefit Long COVID patients by reducing their symptoms and improving their quality of life and if the intervention is good value for money. Patient and public involvement People with COVID lived experience have co-designed this research proposal and the research platform. A lived experience advisory panel will work with us throughout the project and meet regularly to contribute to all aspects of the study. Dissemination Results will be published, presented at conferences and made available for use by other researchers. We will host a study-specific website and Twitter account and will share lay summaries coproduced with our patient partners.",,2023,N/A,3137448.23,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25359,COV-LT2-0006,Impact of COVID-19 vaccination on preventing long COVID: a population-based cohort study using linked NHS data,"Background: While many people fully recover after COVID-19, a substantial proportion continues to suffer from long-term complications such as persistent tiredness, chronic pain or breathing difficulties. Current vaccines prevent severe infections leading to hospitalisations or death, but we do not know yet if they also prevent long-term COVID complications. Aim: Our study will evaluate whether covid vaccination can prevent long COVID. We will first compare the risk for long COVID in adults who received their first dose of a covid vaccine vs. unvaccinated adults. Subsequently, we will compare different covid vaccines to determine whether they can prevent long COVID equally well. Method: We define ""long COVID"" as diagnosis or positive test for COVID-19, which is followed by persistent symptoms that last for >4 weeks. We will use de-identified primary care records to select adults eligible for covid vaccination between January and July 2021 based on UK Government vaccination priority groups. Part 1): For different stages of the vaccine roll-out, we select all adults who were vaccinated in that period. Subsequently, we will find people who were unvaccinated the same time. Since adults who have been vaccinated may have different characteristics and health conditions compared to unvaccinated adults, we will use advanced statistical methods to balance these differences. We will then compare risk for long COVID between vaccinated and unvaccinated adults. Part 2): We will compare risk for long COVID between adults from similar priority groups for covid vaccination, who received different covid vaccines. We will again apply advanced statistical methods to balance differences in patient characteristics for the groups. PPI: A patient suffering from long COVID contributed to the development of the project plan and is a co-applicant for the project. Dissemination: We will share findings with scientists (conferences, manuscripts), NHS, the public and lay audiences.",,2023,N/A,326361,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Vaccines research, development and implementation",Post acute and long term health consequences | Characterisation of vaccine-induced immunity,2021 +P25360,COV-LT2-0014,Cognitive Impairment in Long Covid: PhEnotyping and RehabilitatiOn (CICERO),"Cognitive impairment is increasingly recognised as a major component of long Covid, estimated to be present in 25-75% of affected individuals. This impairment impacts quality of life and the loss of functional ability has major consequences for affected people, their families and the wider economy given people s difficulty in returning to work. We propose a two-stage study for investigation and treatment of ""cognitive Covid"". Stage 1 will determine those aspects of cognitive function that are particularly affected in cognitive Covid and the severity of the impairment. We will also explore the relationship between cognitive impairment and other aspects of long Covid, namely fatigue, anxiety, depression and sleep disturbance. MRI scanning will be used to measure brain structure and connectivity, to identify the brain networks affected in cognitive Covid that may underpin the cognitive dysfunction. Stage 2 will focus on helping people recover from cognitive Covid. This will involve use of rehabilitation strategies aimed at improving function in those cognitive functions identified in Stage 1 as being most affected, and assessing the benefit of rehabilitation on quality of life and people s ability to return to everyday function. These strategies will be co-produced in collaboration with a group of people living with cognitive Covid. At the end of Stage 2 we will produce a freely available ""Covid- 19 Cognitive Recovery Guide"" for affected people, their close contacts and clinicians. In conclusion, cognitive impairment is frequently observed in long Covid but at present little is understood about its nature, or how it can be treated. The sheer scale of the CV19 pandemic makes this a top priority unmet need for healthcare worldwide. The aim of this study is to meet this need and to deliver a treatment plan for affected people which will help them return to normal life and working ability.",,2024,N/A,1801884,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Policy research and interventions,2021 +P25361,COV-LT2-0016,LOng COvid Multidisciplinary consortium: Optimising Treatments and servIces acrOss the NHS (LOCOMOTION),"Long Covid (LC) affects over one million people in the UK, it has various symptoms and impacts daily life. Although there are 83 LC clinics in England, most people have not had access to them, and have to wait long to be seen. We realise the urgency for LC patients to access prompt and appropriate care in clinics and doctors surgeries. Our research aims to produce a gold standard for care by analysing what is happening to patients now, creating new systems of care and evaluating them to establish best practice. Our proposal includes patients working as equal partners and has been developed with LC patients. Their key priorities are correct clinical assessment; advice and treatment; and help with returning to work and other roles. Our research is based on the experience of a wide range of NHS professionals already treating people in ten LC clinics across the UK, led by academics (universities) with links to other LC funded studies. The research will be in three places: LC clinics, at home (including self-monitoring on a mobile device using a set of questions on symptoms built into an app) and doctors surgeries. We will track where patients are being referred or not referred, and learn from the experience of clinics by interviewing patients and recording outcomes. Throughout, specialists in Healthcare Inequality will reach people who are not accessing clinics. We will put in place new processes in clinics and doctors surgeries, monitored throughout to make sure they are the correct standard, accessible for patients and staff, and cost-effective. Comparing findings across our partnership of ten LC Clinics we will learn more about treatment, providing real-time education to other healthcare staff and patients, and establishing a gold standard that can be shared within England and the rest of the UK.",,2024,N/A,4786646.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management | Health Systems Research,Disease pathogenesis | Post acute and long term health consequences | Health leadership and governance,2021 +P25362,COV-LT2-0022,Percutaneous Auricular Nerve Stimulation for Treating Post-COVID Fatigue (PAuSing-Post-COVID Fatigue),"Fatigue is a very common symptom of Long COVID. Feedback from patients has highlighted the devastating impact of post-Covid Fatigue (pCF) on lives as well as the need for novel therapeutic options. Interventions that enhance existing therapies and empower those suffering with pCF to manage their own treatment at home are particularly needed. People with the rare disease, primary Sjögren s syndrome, also show fatigue. We previously demonstrated in such people that non-invasive vagus nerve stimulation (nVNS) at the neck delivered twice daily for 26 days significantly reduced fatigue symptoms. Here, we will extend this work to test whether nVNS can reduce fatigue in adults with pCF. The vagus nerve has a branch which supplies the skin around the ear canal. Stimulating the ear can be easily and safely self-administered at home using a handheld battery-powered transcutaneous electrical nerve stimulation (TENS) device, available over the counter without prescription. We will focus on people diagnosed with COVID19 but not requiring hospital in-patient treatment. In this study, 96 participants with pCF will be randomly assigned to one of three study groups. One group will asked to stimulate the part of the ear containing the vagus nerve. For comparison, the other two groups will either be asked to stimulate a part of the ear that does not contain the vagus, or given an electrode that is inactive. After 8 weeks, changes in fatigue severity will be measured using questionnaires and wearable technologies. We will also use lab-based tests to measure changes in brain circuits. From week 9, all participants will switch to receive nVNS until week 16 and the above measurements repeated.",,2024,N/A,896252,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25363,COV-LT2-0027,IMMUNE ANALYSIS OF LONG COVID TO INFORM RATIONAL CHOICES IN DIAGNOSTIC TESTING AND THERAPEUTICS,"Working with the Long COVID (LC) community, the applicants have argued the need for better understanding of the underlying mechanisms. With a more granular understanding of the precise mechanisms underpinning the diverse disease manifestations, one could both implement definitive diagnostic tests (which have been lacking) and identify those pathways implemented in the disease process and better understand the therapeutics likely to be most effective, an approach of 'less observation, more intervention'. Our studies encompass decades of work in autoimmunity, viral immunity, and the interface between the two in infections such as Chikungunya. Our starting point for this study is outreach to individuals who were not hospitalised but now have LC. Investigations start with the assumption that studies to define specific immune mechanisms in blood samples will supply diagnostic tests for healthcare application, as well as pinpointing the known therapeutics most likely to offer successful treatment. We hypothesised that LC may be the result of direct organ damage by the virus, reservoirs of persistent virus (for example in the gut), subsets of white blood cells in the immune system which are dysregulated following infection, or, as in Chikungunya, viral infection has triggered specific autoimmunity - that is, antibodies and/or T cells targeting self tissues to cause symptoms. We will invite study participants through adverts and through support groups, asking them to give a blood sample to look at three specific questions of immune dysregulation: 1. What is the evidence for disrupted white blood cell subsets in LC? 2. What is the evidence for RNA changes in T cells from people with LC, indicating an altered programming as suggested by the many who find that their allergy profile has changed 3. What is the evidence for specific autoimmunity correlated with LC? Deliverable: evidence-based diagnostic tests at the cellular, RNA and autoantibody level",,2024,N/A,791801.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P25364,COV-LT2-0043,"STIMULATE-ICP (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)","Long Covid is affecting over a million people in the UK. The wide-ranging symptoms are disabling, and need joined-up care from specialists, hospitals and community services. Over 80 long COVID clinics have been established but we need to better understand, diagnose and treat the disease. We will design and test the best ways to care for people with long COVID. We will bring together six regions: Derby, Exeter, Hull, Leicester, Liverpool, and London, and include the Royal College of General Practitioners policy team, health professionals and academics. Four patient organisations have helped to develop this proposal. They will be involved across the project from design to dissemination. To improve recovery, we will work out what long COVID is, how to diagnose it and how to manage it. The data and findings will be easily accessible to aid further research and service improvement. We will interview patients and health professionals and analyse data from NHS records. This will inform our understanding of patterns of long COVID and the outcomes of current clinical practice. Usual care involves basic investigations such as blood tests and self-management of rehabilitation using a website https://www.yourcovidrecovery.nhs.uk/ . We will recruit over 4,500 patients in the largest long-COVID trial to-date. We will compare a new pathway including community-based, comprehensive MRI scan (CoverscanTM) and enhanced rehabilitation (Living with COVID RecoveryTM) with usual care. We will also test different drugs, including aspirin, colchicine and loratadine/famotidine. We will measure effects of three months treatment by symptoms, mental health, return to work and other important outcomes. With patients, we will co-develop means to improve patient access to the right care at the right time in the right place, including health professional training. We will consider the aspects of long COVID care which might improve care for patients with multimorbidity and long-term conditions.",,2025,N/A,9752888.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management | Clinical trial (unspecified trial phase)",2021 +P25365,COV-LT2-0073,Quality-of-life in patients with long COVID: harnessing the scale of big data to quantify the health and economic costs,"We want to understand the impacts of long COVID on the quality-of-life of people who have developed this condition. For many health conditions, researchers ask people to fill in standardised surveys which measure quality-of-life, which help them understand how much the condition is affecting people. These kinds of measures are used in planning the resources for health systems, because they allow a standard way of comparing different health conditions, and, if people fill them in repeatedly, tracking changes in wellbeing over time. These quality-of-life measurements are not currently available for people with long COVID who did not need to be hospitalised during their COVID-19 episode. Our study aims to collect these measurements, by using a smartphone app linked to a patient s GP records. We will ask people to voluntarily participate in the study and use the app, and if they do so to give their consent for filling the questionnaires and for linkage to their health records. These results will tell us if long COVID has different quality-of-life impacts among different age groups, ethnicities, geographic regions, or because of any underlying health conditions. We will convert the results into standardised measurements that are used in the NHS to assess the impact of illnesses. This means they will be useful for working out how much the effects of long COVID cost the health service, and how we should prioritise interventions such as vaccines to avoid more people getting long COVID. Together with other researchers studying long COVID we will provide results to support long-term care. At all stages we will work with people affected by long COVID to ensure their input is central to designing the study plans and interpreting the outputs.",,2023,N/A,947128,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P25366,NIHR129791,Healthy Dads Healthy Kids in prisons: a feasibility study and pilot for an intervention to improve father 'Äì child relationships,"People who have been imprisoned (95% of whom are men) are at high risk of increased mortality and poor health. Children of imprisoned parents have poorer health, education and offending outcomes compared to other children. Around half of people in custody lose contact with their families while imprisoned. Delivering effective relationship-promoting interventions to fathers in custody can improve the mental health, wellbeing and self-esteem of fathers and their children, break possible inter-generational cycles of disadvantage, and reduce recidivism and inequalities. A program known as Healthy Dads, Healthy Kids (HDHK) has shown significantly improved health outcomes and behaviors in fathers and children when delivered in community settings. For the first time internationally, we have adapted the program for delivery in prisons (HDHK-P). HDHK-P is designed to facilitate children'Äôs contact with their fathers and uses enjoyable joint physical activity and healthy eating sessions to improve their physical and mental health, and father-child relationships. Completed development work means a first version of HDHK-P is available, which requires some further adaptation following changes in prison regimes during COVID-19. Physical Education Instructors (PEIs) in two prisons will then be trained to deliver the program. Work package 1 (WP1) will adapt the current version of HDHK-P to reflect the 'ÄòCOVID prison context', before testing the feasibility of delivering the program to groups of fathers and their children in two prisons. It will then further refine the program content and delivery process for the WP2 pilot. Meetings with key stakeholders in the two prisons and with those supporting men'Äôs families within the community will inform COVID-related adaptations, identify any recruitment and implementation issues for wider delivery, and will allow us to explore the acceptability and feasibility of the proposed research methods. WP2 will pilot the optimized HDHK-P over two deliveries (A and B) in the same two prisons (four deliveries in total) and will assess the research procedures for a future full-scale evaluation. We will conduct: observations of program sessions; in-depth interviews with the prison Physical Education Instructors facilitating program delivery, the participating fathers and the adults accompanying the children to participate in the sessions; and focus groups with the participating children. Baseline and follow-up measures (at 9 weeks and 6 months for both A and B deliveries, and 9 months for A deliveries only) will collect data on fathers' mental health or wellbeing (likely future full-scale evaluation primary outcome), and a selection of the following (to be finalized in WP1): father and child self-esteem, father discretionary food and drink canteen purchases, father and child self-reported dietary intake, father and child physical activity, father and child weight, child screen time, quality of father-child relationship from both perspectives, and child socio-emotional health and self-worth (potential future full-scale evaluation secondary outcomes). We will also conduct a wider prison consultation with regard to a future full-scale evaluation and/or roll-out (WP3). An optimized HDHK-P program will be a key output of the study. Progression to a full-scale evaluation will make use of a red-green-amber system designed to assess positivity about the program among stakeholders, and aspects of delivery and sustainability that are pertinent to such an evaluation being possible. If there is considerable support for HDHK-P, but a future full-scale evaluation looks to be unfeasible, the possibility of embedding the program in the Scottish'Äôs Prison Service'Äôs Family Strategy will be explored.",,2024,N/A,552880.81,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Prisoners | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25367,NIHR129901,Which health visiting models in England are most promising for mitigating the harms of maternal related Adverse Child Experiences?,"Background: Parental alcohol and substance misuse, mental health problems and domestic violence and abuse are common adverse childhood experiences (ACEs) which are associated with worse health and development outcomes for children. As the data we are using captures children whose mothers (not fathers) had a hospital admission for one of these ACEs, we call them 'maternal ACEs'. Health visiting is designed to assess, monitor and support children affected by ACEs, including maternal ACEs, as well as deliver universal care to every child in England. However, we know little about the coverage, intensity, type and costs of health visiting in practice, to what extent health visitors support families living with maternal ACEs and how this is balanced with providing care to all families in their local area. Aims and objectives: To determine 1) which factors determine the coverage, intensity, type, resource-use and cost of health visiting services received by families with and without maternal ACEs; 2) which health visiting models are most promising for mitigating the impact of maternal ACEs; and 3) what these results mean for local and national decision-makers and families. Methods: The study is based on a subset of all births in England 2015-2019. We have to use a subset of all births because only about 25% of local authorities in England have sufficiently complete health visiting data to analyse. We will identify families exposed to maternal ACEs in longitudinal hospital admissions data on mother-baby pairs (HES) linked with health visiting data (Community Services Dataset; CSDS). We will combine this with information on local area need (e.g. deprivation) and surrounding services (e.g. the Family Nurse Partnership). We will use a national survey of practice in all 152 local authorities to collect extra information not available in CSDS and to extend our data beyond the subset of local areas with complete data in CSDS to all local authorities in England. We will conduct in-depth qualitative case studies in up to 6 local authorities , including interviews with Directors of Public Health, health visiting commissioners and managers, health visitors and mothers, plus analysis of locally held administrative data. Work package (WP)1: Months 1-24. We will produce a taxonomy of 3-5 'Äòmodels'Äô of HV, grouping all 152 local authorities in England according to similarities in coverage (universal / targeted), intensity (e.g. patterns of repeat contact) and type (face-to-face, phone, group) of services delivered to families with/without maternal ACEs. We will i) describe indicative resource use and cost for each model; ii) generate detailed descriptions of factors associated with differences between local authorities using qualitative case study methods in up to 6 areas of England s (e.g. local area need/surrounding services) and iii) use key stakeholder input, including with groups of parents who have relevant lived experience to create robust hypotheses about how each model works for families exposed to maternal ACEs. WP2: Months 25-42. We will use the taxonomy to evaluate associations between different HV models and select child and maternal outcomes, for families with/without maternal ACEs. Outcomes captured in HES-CSDS will include child development (Ages and Stages Questionnaire), child safety/harm from adverse caring environments (child injury or maltreatment-related admissions), and post-birth maternal ACEs (adversity-related hospital admissions in mothers). We will explore differences the associations through qualitative work and engagement with key stakeholders. In year 4, we will use updated data and stakeholder engagement to assess the meaning, validity and generalisability of our results, including for a post COVID-19 context. WP3: Months 42-48. We will review existing HV quality metrics, based on integration of findings from WP1 and 2, and provide evidence summaries in order to inform local and national implementation of services. Impact/dissemination: We will work collaboratively to disseminate our findings to key stakeholders and families. The evidence will inform the modernisation of the Healthy Child Programme, and be used by local leaders when planning and revising their Start for Life Offer for all babies and very young children in their areas.",,2026,N/A,1091331.35,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P25375,NIHR132895,PREdictors of COVID19 OUtcomeS (PRECIOUS),"BACKGROUND: COVID-19 has impacted >767 million people worldwide. Addressing the long-term impacts, areas of rehabilitation need within the COVID-19 population and establishing costs of care are a priority. AIM: Create an international, multidisciplinary COVID-19 database, synthesising long-term outcomes, predictors and costs. OBJECTIVES: Describe: 'Ä¢ long-term outcomes and predictors, by International Classification of Functioning, Disability and Health (ICF) domains 'Ä¢ financial costs of COVID-19 'Ä¢ findings to patients, public, health professionals and researchers METHODS DESIGN: Systematic identification and recruitment of COVID-19 datasets, creating an international multidisciplinary database to support individual participant data (IPD) meta-analysis. Patients & Public Involvement (PPI) and health professionals will inform methodological decisions & dissemination. STAGE 1: A systematic search of electronic databases, trial registries, grey literature, forward & backward citation tracking, with no language restrictions, for COVID-19 cohort studies and randomised controlled trials, from any setting, where assessments are recorded >=1 month of symptom onset. Investigators will be invited to contribute IPD. Data will be securely stored, cleaned & mapped to ICF domains. STAGE 2: Demographic, socioeconomic, clinical, treatment, resource use data (in natural units), and long-term outcomes will be extracted. Our existing algorithm will support data standardisation within ICF domains. Planned IPD meta-analyses will consider the effects of demographic, socio-economic, comorbidity, clinical & treatment variables on (A) long-term outcomes using a one-step regression approach; and (B) resource use (individual, healthcare & community costs). Data permitting, a prediction algorithm will be developed for clinical use. FEASIBILITY: >8000 IPD (14 studies; 10 countries) secured and is expected to increase. OUTCOMES, IMPACT & DISSEMINATION will describe the COVID-19 population in whom evidence is based, highlight gaps, applicability of findings & direct future research; map expected long-term impacts; provide information for people with COVID-19, families, GPs, clinicians, researchers & policy makers; inform resource allocation, prognosis and avenues for early intervention; develop a prediction algorithm for clinical use; quantify the cost of COVID-19, direct resources and support to areas of need. A legacy dataset will facilitate future analyses. Outputs will be delivered via a website, peer-reviewed papers, engagement with health professionals via existing networks, people with COVID-19 & their families via PPI led activities & social media. DURATION: 2 years ETHICS: University ethics approval is pending for anonymised data analysis. IRAS registration has been requested. Data sharing will be subject to local approvals. Data contribution, preparation and analysis will adhere to a data management plan. COSTS: An international IPD database will permit efficient analyses. Costs support experienced IPD meta-analysis rehabilitation researchers, statisticians, health economists, clinical researchers in long-term conditions, rehabilitation (OT, Physio, SLT, Audiology), respiratory medicine, infectious diseases and PPI partners. Our shared legacy database will reduce research waste.",,2023,N/A,745056.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Policy research and interventions,2021 +P25379,NIHR133712,NIHR Global Health Research Group on Promoting Children'Äôs and Adolescent'Äôs Mental Wellbeing in sub-Saharan Africa.,"Research Question What is the effectiveness of a culturally adapted whole school mindfulness intervention to promote mental wellbeing amongst children and adolescents 7-14 years (CA) in sub-Saharan Africa (SSA)? Background Poor mental wellbeing is the leading cause of illness among adolescents in SSA, with an estimated prevalence rate of 1 in 7. However, CA mental wellbeing is an under-researched issue; there is a lack of community awareness and few evidence-based interventions to promote it. CA mental wellbeing has been negatively impacted by COVID-19, making it even more urgent to find culturally acceptable, affordable, and cost-effective interventions to sustainably improve CA wellbeing. Aim To identify, design, implement, and evaluate a culturally acceptable, affordable and cost-effective mindfulness intervention for promoting CA mental wellbeing. Objectives Objective 1: Identify and build networks of policy actors, implementers and community members, including CA, that have a stake in improving CA mental wellbeing. Objective 2: Identify current policies for promoting CA mental wellbeing in Ethiopia and Rwanda and examine their effectiveness. Objective 3: Provide an enhanced understanding of the distinct mental wellbeing challenges that face CA and how these challenges are affected by gendered power relationships. Objective 4: Co-design a whole-school mindfulness intervention for implementation in schools to promote CA mental wellbeing that is culturally acceptable to policy actors, implementers, and communities, including CA. Objective 5: Generate evidence on the intervention's efficacy, cultural acceptability, affordability, and cost-effectiveness ready for a multi-centre trial. Objective 6: Build an African led transdisciplinary global health research group on promoting CA mental wellbeing and population wellbeing more generally. Methods Co-design and implement an affordable and acceptable whole-school intervention to promote CA mental wellbeing with policy actors and community members, including CA. Evaluate the intervention using critical realist principles combined with a quasi-experimental control trial enabling an understanding of what works for whom in what circumstances. A deep understanding will be developed by researching CA's, their families', communities' and teachers' experiences, intervention performance, and implementation costs. Capacity will be built by training future African research leaders in multidisciplinary applied health research in four overlapping phases: 1 context and situational analysis (year 1); 2 train teacher educators and teachers in mindfulness and co-design an intervention with policy actors and community members, including CA; 3 deliver an intervention in school delivered by teachers designed to promote CA mental wellbeing (year 3); 4 an impact evaluation (year 4). Impact 1 Through the intervention, promoted CA wellbeing. 2 Involving policy actors, communities, including CA, and economic analysis to ensure the affordability, cultural acceptability, and cost-effectiveness of the intervention, thereby providing a pathway for evidence take-up with an intervention ready for a multi-centre trial. 3 Enhanced the capacity of African researchers to lead and conduct research and implement interventions to promote mental wellbeing, thereby building skills to sustainably transform the promotion of CA mental wellbeing in sub-Saharan Africa.",,2026,N/A,3515425.12,Human Populations,Black,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25380,NIHR133788,HElping Alleviate the Longer-term consequences of COVID-19 (HEAL-COVID): A national platform trial,"Research question: Can interventions in the convalescent phase of COVID-19 improve longer-term outcomes? Background: COVID-19 is a new disease for which the natural history remains uncertain. However, recent data suggest that >10% of patients die and >25% of patients require readmission to hospital within 4 months of discharge. A unique feature of COVID-19 is the high incidence of cardiovascular and pulmonary complications including venous thromboembolism, persistent lung inflammation, and pulmonary fibrosis; These may not be confined to the acute phase of the illness, but rather may also occur during the convalescent phase of the illness, thus providing a major contribution to the ill-defined syndrome 'Äúlong COVID'Äù. Aims and objectives: The primary aim of the proposal is to set up a pragmatic phase 3 adaptive clinical trial platform designed to provide reliable evidence on the efficacy of post-hospitalisation treatments aiming to improve clinical outcomes from COVID-19. Methods: We propose to establish a clinical trial platform, integrated into the current national COVID-19 clinical characterisation (ISARIC4C, GenoMICC, PHOSP-C) and acute clinical trial landscape (RECOVERY, REMAP-CAP, PRINCIPLE). The platform will be an pragmatic open-label adaptive trial, with the flexibility to add intervention arms as evidence from partner studies emerges. The primary endpoint of the trial will be hospital free survival at 12 months after randomisation, and will be assessed using linkage to routinely collected clinical data via NHS Digital. Secondary endpoints will include patient reported outcome measures (based on Core Outcome Sets for COVID-19 and long-term follow up for pattens with acute respiratory failure) and quality of life assessment. Timelines for delivery: Study set-up will run in parallel with this grant application and with a planned start date of March 2021. The study is proposed as a UK-wide national Urgent Public Health platform trial; set-up to close-down is projected to take three years. Anticipated impact and dissemination: The aim of the trial is to change the standard of care for patients with COVID-19 by determining which interventions do and do not alter longer-term clinical outcomes. We propose to disseminate the outputs of the study to both patient and public audiences, as well as healthcare audiences via open access peer reviewed publications, presentations to conferences as well as patient/participant groups, press releases (where appropriate), social media, and clinical management guidelines. In addition we aim to establish an online digital patient community to ensure the findings of our work are effectively shared with people who experience Long COVID.",,2024,N/A,5111957.77,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Post acute and long term health consequences | Phase 3 clinical trial | Therapeutic trial design",2021 +P25382,NIHR134986,Realist Review: Health visiting in light Of the COVID-19 Pandemic Experience (RReHOPE),"Research question How can the organisation and delivery of health visiting services in the UK be improved in light of COVID-19 pandemic, to provide equitable, effective and efficient services for young children and their families? Background Health visiting services are an essential part of the UK'Äôs support structure for young children, helping to ensure every child has the best start in life. Whilst child health programmes share the same goals, there are different government policies across the four nations of the UK and competing opinions about how services are best organised and delivered. There is a paucity of research about both organisational arrangements and about how health visitors practise in order to achieve the best outcomes. COVID-19 tested health visiting services in profound ways. Services rapidly adapted in response to the situation, with many providers developing innovative ways to ensure families continued to receive support through extraordinary 'Äòlockdowns'Äô. Some innovations will have worked better for some people, in some contexts, than others. Furthermore, the impact of the pandemic on families and young children has been far-reaching and uneven, with important implications for post-pandemic health visiting services. There has been lots of data published since the start of the pandemic, but there is a need to synthesise this to understand how the organisation and delivery of health visiting services can be improved for a stronger post-pandemic recovery. Methods We will undertake a realist review of the literature relating to health visiting services during the COVID-19 pandemic since March 2020. We have chosen a realist review because health visiting services are a complex intervention and the impact of the pandemic will have been different for different people in different contexts. We will follow Pawson'Äôs five iterative stages, namely: 1) locate existing theories; 2) search for evidence; 3) article selection; 4) extract and organise data; and 5) synthesise evidence and draw conclusions. We will recruit a stakeholder group of individuals, organisations or communities that are representatives, in different parts of the UK, of patients and the public, providers, commissioners, policy-makers, researchers and policy advocates. This group will advise and give us feedback throughout the project. Our review, which will follow the RAMESES quality standards, will last 18 months from June 2022, by which time we expect there to be a considerable body of evidence to include and synthesise. It will consider the differences in policy and service delivery across the UK and analyse, where possible, the differences in impact across the four constituent countries. Impact Our findings will be used to provide recommendations for improving the organisation and delivery of ongoing post-pandemic recovery of health visiting services in different settings, for different groups. We will collaborate closely with the Institute of Health Visiting (iHV) and our stakeholder group to ensure our findings are developed into a range of outputs suitable for a variety of audiences. These will include academic papers, a 'how to' publication and user-friendly summaries. Our stakeholder group, as individuals and organisations who are interested in the messages arising from our work, will help amplify our message, getting our research to different members of the policy and practice community in different ways.",,2023,N/A,333874.37,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P25385,NIHR135639,Placebo-controlled randomised trial of tecovirimat in non-hospitalised Monkeypox patients (PLATINUM),"This protocol describes a scalable, double-blind, placebo-controlled, randomised trial among non-hospitalised adults and children with laboratory-confirmed monkeypox virus disease in the United Kingdom. Eligibility and randomisation: Patients will be identified following clinical assessment and laboratory confirmation of monkeypox infection as part of usual NHS clinical care. All eligible and consenting patients will be randomly allocated (1:1) to receive tecovirimat or matching placebo for 14 days, each to be given in addition to the usual NHS care. Efficacy outcomes: The primary clinical efficacy endpoint is the time to resolution of active lesions. Secondary efficacy endpoints are time to complete lesion resolution, and the time to negative cultures for monkeypox virus in throat and lesion swabs. For the main analyses, follow-up will be censored at 28 days after randomisation. Additional information on longer term outcomes may be collected through review of medical records or linkage to medical databases such as those managed by NHS Digital and other health care organisations across the UK. Additional assessments may be conducted following the end of the main assessment period of the study (28 days) to assess complete resolution of monkeypox symptoms and other relevant adverse events. Safety: Serious adverse events, non-serious adverse events of special interest, and reasons for stopping study treatment will be recorded and will be reviewed by medical staff at the Central Coordinating Office. Suspected Unexpected Serious Adverse Reactions (SUSARs) to study medication (e.g., Stevens-Johnson syndrome, anaphylaxis, aplastic anaemia, etc.) will be reported in an expedited fashion. Data collection: To facilitate patient isolation and infection control, and participation by clinicians and patients, data collection and all other trial procedures are streamlined and focused on those aspects critical to participant safety and the reliability of the study results. Informed consent, randomisation and follow up will be conducted remotely by telephone or video and data will be recorded by electronic methods by participants and trial staff. Numbers to be randomised: The rates of clinical and microbiological resolution are uncertain for monkeypox in general, and in particular for the current epidemiological context. Sample size estimates using data on the natural history of Congo Basin clade monkeypox indicate that randomisation of 500 individuals would provide at least 85% power and a two-sided a of 0.05 to detect a 40% improvement in the rate of lesion resolution at day 28 (account for one interim analysis and approximately 10% losses to follow-up). Monitoring of blinded event rates will be used to re-estimate sample size requirements as data from the trial accrue.",,2023,N/A,1230477.65,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Poxviridae,,,,,,,,,Mpox,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,"Therapeutics research, development and implementation","Development of equitable, accessible, safe & effective therapeutics",,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2022 +P25387,NIHR150393,Exploring and grouping COVID-19 pharmaceutical interventions to determine mechanisms of action and endotypes of response,"Research question Do three novel therapeutic COVID-19 therapies work through different biological mechanisms and can we predict responders and non-responders to each therapy. Background SARS-CoV-2 has caused over 4 million deaths globally. Despite the success of vaccine development, vaccination is not ubiquitously available. The inequity of vaccination dissemination across the world, and the evolution of new strains capable of escaping vaccine protection has meant that novel drugs are still necessary to combat severe disease. This project utilises the ACCORD phase II clinical trial data that assesses the rapid testing and efficacy of novel drugs for COVID-19 treatment against the Standard of Care (SoC). The 3 novel drugs are: Bemcentinib, MEDI3506 'Äì Tozorikumab and Zilucoplan, of which their biological mechanisms of action in COVID-19 are still unknown. Aims and objective We aim to identify biological mechanisms underpinning the efficacy of three novel therapies for COVID-19. We will identify which features of the disease predict clinical response and explore the biological differences leading to different treatment outcomes. We will further build prognostic models to predict patient response to each novel drug and assess the most salient features driving drug response. The ability to predict and understand response to these novel drugs will improve patient recovery time and ease strain on healthcare resources. Methods Multiple data types have been generated from patients receiving one of the three COVID-19 therapies compared to patients receiving contemporaneous SoC. Patients'Äô clinical responses to the therapies have already been analysed, enabling the comparison of clinical response and quantification of clinical efficacy. All three treatments demonstrated a signal of clinical benefit however these differed in the size and nature of effect. This project aims to improve our understanding of these clinical effects through the analysis of RNA-Sequencing, inflammatory/immune proteomics, viral load, pharmacokinetics and patient phenotype. Bioinformatics analysis will first be applied to transcriptomic data to identify differentially expressed genes and the biological mechanisms that are impacted by the trial treatments. Gene expression results will be correlated across other data types. In addition machine learning will be applied to ascertain the most important predictors of response to each treatment to if patients are likely to respond well to a particular treatment and to create new stratification tools to target treatments. Timelines for delivery This project will last 13 months. To deliver the project in this timeframe activities will be coordinated in parallel. Anticipated impact and dissemination It is anticipated that this work will lead to multiple high impact publications as well as conference presentations. More practically, this work will lead the way in determining how novel COVID-19 drugs biologically impact patients and could lead to a reduced burden on healthcare systems through the more efficient prescription of COVID-19 therapies. These results will directly inform the design of Phase 3 trials of the individual therapies including patient inclusions and endpoint selections. They will also inform on the potential application of the treatments for other respiratory infections beyond COVID-19.",,2024,N/A,209142.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase)",2023 +P25394,NIHR155209,"A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) - Influenza"," -Research questions Overall platform: What are the most clinically and cost-effective pharmaceutical interventions for patients of all ages hospitalised with confirmed influenza? Domain specific (at outset): In adults and children hospitalised with confirmed influenza 'Ä¢ What is the optimal anti-viral treatment strategy? 'Ä¢ Do corticosteroids improve outcomes? 'Ä¢ What is the optimal immune modulation strategy in the severely ill? -Design: An established UK multifactorial Bayesian adaptive platform trial for community acquired pneumonia, also recruiting internationally, using response adaptive randomisation. -Setting: 150 hospitals throughout the UK admitting patients with influenza including under-served regions and communities. -Target population: Adults and children admitted to hospital acutely unwell with confirmed influenza. Exclusion criteria: Patient is expected to be discharged from hospital today or tomorrow Previous participation in this trial within the last 90 days -Interventions being assessed at outset Influenza antiviral domain 'Ä¢ Oseltamivir daily for 5 days 'Ä¢ Oseltamivir daily for 10 days 'Ä¢ Baloxavir on days 1 and 4 'Ä¢ Combination of Oseltamivir daily for 5 days and Baloxavir on days 1 and 4 'Ä¢ Combination of Oseltamivir daily for 10 days and Baloxavir on days 1 and 4 Initial comparator is no antiviral treatment. Corticosteroid domain 'Ä¢ Dexamethasone for 10 days Comparator is no corticosteroid treatment Immune modulation domain 'Ä¢ Tocilizumab 'Ä¢ Baricitinib Initial comparator is no immune modulation treatment. The design allows comparative effectiveness between interventions in a domain to be estimated. The multi-factorial design allows interactions between treatments in different domains to be evaluated. Measurement of outcomes & costs: Primary: 28-day organ support-free days, including mortality Secondary: Symptom severity, WHO ordinal scale, need for intensive care (ICU) admission, need for ventilation, duration of ICU and hospital stay, 90- and 180-day mortality, serious adverse events / reactions, health-related quality of life (EQ-5D-5L), disability (WHODAS), cost effectiveness at 6 months. Development of anti-viral resistance. Statistical methods: A Bayesian hierarchical model, with pre-defined triggers for efficacy and futility (to control), superiority and equivalence (to other treatments). Stratification will allow separate treatment effects to be estimated for critically ill and non-critically ill patients, as well as adults and children. Timelines for delivery: International recruitment has begun (antiviral n=150, corticosteroids n=144). Approvals for UK ICU recruitment are in place. The adaptive Bayesian design allows conclusions as soon as triggers are reached rather than fixed sample sizes. International participation (Southern hemisphere) will ensure year-round recruitment and rapid results for a seasonal illness ahead of rises in UK cases. Anticipated impact and dissemination: REMAP-CAP changed practice globally, saving lives in severe COVID-19, and can impact influenza treatment in the same way.",,2024,N/A,3518805.11,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2022 +P25397,NIHR159200,'ÄòGoing dark'Äô or under the radar? Challenges and opportunities for local authorities and dark kitchens in ensuring food safety for the public,"The use of online platforms has become an entrenched part of the UK food system, bringing a range of risks and opportunities to food businesses, consumers, non-traditional food businesses, and the regulatory regime. The pandemic COVID -19 accelerated the growth of dark kitchens as a reflection of the economic destabilisation at the time. They are characterised by having no spaces for local consumption, no direct contact with the public and selling exclusively through online platforms. The increasing number of new entrants and ad-hoc food vendors operating from dark kitchens make monitoring and oversight highly challenging. Food allergen management is highly challenging especially within a multi-brand dark kitchen model operating with several brand / cuisine types operating from the same kitchen. The meal production could be done in parallel or at different times during the day. This elevates the risk of cross contact especially food allergens and unknown ingredients. There is also a risk that uncertified vendors may operate under the radar of local authorities and raises concerns over food safety issues. Our proposed study aims to answer the following Research Questions: (i) How do Local Authorities identify dark kitchens? (ii) What are the challenges and opportunities for food safety inspections in dark kitchens? Aim: This study aims to assess the challenges and opportunities in identifying dark kitchens and to identify potential interventions to increase food safety compliance in dark kitchens by working with local authorities, dark kitchen owners and dark kitchen tenants. The findings from this study will inform a larger piece of public health research on food safety in dark kitchens. In our larger NIHR grant application, we aim to trial potential interventions for food safety implementation / inspection (e.g., food hygiene inspection for shared premises) with dark kitchen owners and tenants. Plan of investigation: Work Package (WP) 1a: An exploratory desktop review will be conducted to identify dark kitchens in a local authority area. Facebook Marketplace, online delivery platform (JustEat), Food Hygiene Rating Scheme and Google¬Æ Street View will be used to identify and classify possible dark kitchens. WP1b: An online survey and two focus group discussions will be conducted with local authority officers. LA officials will be recruited through Regional Groupings and two focus group discussions will be conducted to generate a richer qualitative dataset to help understand LA officials'Äô experience and insights in identifying dark kitchens and food safety inspection and implementation of food safety standards in dark kitchens. WP2 will explore the challenges and opportunities faced by dark kitchen owners and tenants. We aim to recruit 15 dark kitchen owners and tenants. Topics of discussion with dark kitchen owners and tenants will focus on identifying potential interventions to increase compliance in the food ecosystem to ensure food safety standards are enforced. Timelines: WP1: March 'Äì April; WP2: April 'Äì May; Analysis and final report: July 'Äì August. Our study will provide underpinning evidence for future food safety inspection and implementation in dark kitchens to help address public health issues. Dissemination activities will include academic publication, workshop, policy briefs, The Conversation/media and presentations at relevant conferences.",,2024,N/A,63894.89,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2024 +P25399,NIHR202753,Development and refinement of an online group-based clinical neuropsychology rehabilitation programme to improve psychological wellbeing and quality of life after acquired brain injury.,"Context: Acquired brain injury (ABI) is a type of brain injury caused by medical conditions (e.g., stroke) or injuries (e.g., traffic accidents). In the UK, 1.4 million people live with the consequences of ABI, which can be life-long, costing the economy £15 billion annually (10% of the NHS annual budget). Approximately 20% of ABI survivors experience emotional and/or thinking skills problems. These problems can impact people's return to hobbies and work, and increases risk of isolation, resulting in psychological distress and reduced quality of life. The problem: Neuropsychological rehabilitation (a type of psychological therapy) is useful in treating such problems, but is typically delivered face-to-face in individual or group sessions. However, due to a lack of NHS resources, not all ABI survivors get the help they need. Furthermore, limited clinic space and COVID-19 restrictions mean group sessions cannot always be provided safely, if at all. Our solution: Online group-based neuropsychological rehabilitation may provide an alternative, that can fit around busy lives (e.g., for ABI survivors who work), group people according to shared experiences (e.g., young survivors), or overcome issues of physical contact (e.g., those with mobility problems). Despite possible advantages, such ABI-specific neuropsychological rehabilitation has not been systematically developed or evaluated. Our aim To develop an online, group-based neuropsychological rehabilitation programme to improve psychological wellbeing for ABI survivors, and to test whether patients find it useful and acceptable, and the NHS can deliver it. Methods To develop the programme (or ""intervention""), we will: 1. Review previous research to understand how neuropsychological therapies are delivered, by whom, in which contexts, and who benefits. This will enable us to produce an initial plan/blueprint for the new intervention. 2. Develop this plan/blueprint further, to produce an intervention manual, by: (i) surveying ABI survivors and stakeholders to explore different views regarding group-based online interventions (ii) seeking feedback from an advisory group of professional and patient experts (iii) conducting interviews with ABI survivors and stakeholders to critique and refine the intervention. 3. To test the intervention, we will deliver it to two groups of approximately 4-6 patients each. We will seek feedback on acceptability and feasibility of delivering the intervention from ABI survivors and therapists, enabling further modifications of our intervention. Patient and Public Involvement (PPI) PPI underpins our project design and delivery. The idea originated from our clinical work and patient feedback, and this project was co-designed by our PPI Lead. We have listened to feedback from our ABI survivors and carers' PPI group, who think it is vital they get neuropsychological therapies targeting psychological wellbeing, and are keen to explore online options. Dissemination Results of each stage will be communicated to participants (via accessible newsletters), published in scientific journals and presented at conferences.",,2024,N/A,218850.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health service delivery",2022 +P25402,NIHR203106,Hearing from the unheard: impact of long-COVID in minority ethnic groups in the UK (Hi-COVE),"Long Covid is the name given to not recovering quickly after getting Covid-19, and experiencing ongoing symptoms such as extreme exhaustion, difficulty breathing and memory or concentration problems. These persistent symptoms affect people s physical and mental health, and cause significant disruption to daily lives and people s sense of who they are. Ethnic minority groups tend to suffer more from Covid-19, e.g. more infections, with worse severity and death rates, especially for Black, South Asian and Arab people. Although so far there is no evidence that Long Covid is higher in these groups, lack of trust in healthcare, racism, stigma, discrimination, and language barriers experienced by these groups may hinder reporting of Long Covid symptoms and care, and may mean they experience worse consequences of Long Covid. Current Covid-19 care management is not yet sufficiently informed by the needs of ethnic minorities, hindering equal access to quality healthcare. Minorities many times turn to families, alternative support systems such as local networks, religious and cultural communities, as well as traditional healers. Our research will look to understand views and experiences of underrepresented groups; alternative support systems used as well as what support they want and need from health care services. Findings will help us to imagine better healthcare services for these groups. The research has been informed by patients and the public. We will recruit Black, South Asian, and Arab participants (up to ten of each group) for interviews to explore their views and experiences of Long Covid. We will aim to include a wide variety of people to include different: ages, gender, severity of symptoms of Long Covid, including both those diagnosed with Long Covid(who may have accessed healthcare) and those who self-report Long Covid (to ensure we are inclusive of those who fall through the gaps of healthcare). Interviews will explore the following: (a) What people think about their symptoms, (b) What support and treatment people prefer, (c) How Long Covid has impacted their lives, (d) Access to support systems (friend, family, community, healthcare systems), and (e) Challenges to accessing appropriate support. Our findings will be used to start conversations with Long Covid patients, healthcare professionals and key stakeholders to design better healthcare services for underrepresented groups. Findings will be shared with different groups, including patients, healthcare professionals, community groups, non-healthcare professionals and commissioners, and policy makers. We will deliver presentations, write reports, develop short-videos and/or photo-texts with our artist-collaborator. All of which will be available to the public on a dedicated website, co-created with Long Covid patients. These findings will inform content for a training workshop to support healthcare professionals to better understand the needs of people living with Long Covid from ethnic minority backgrounds.",,2023,N/A,156720.54,Human Populations,Black | Other,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25403,NIHR203121,Covid-19 vaccination in inflammatory conditions treated with immune suppressing drugs: a study of clinical effectiveness and vaccine safety using data from the Clinical Practice Research Datalink (CPRD).,"One in fifty people have inflammatory conditions such as rheumatoid arthritis. These conditions result from the immune-system, that usually fights off infections, getting out of control and damaging the joints and other parts of the body. To stop such damage from occurring, people with these conditions take medicines that dampen the immune-system. However, this not only increases their risk of getting very unwell with infections including with Covid-19, but it also means that there may be less benefit from vaccinations. There is also concern among patients that vaccinations may flare-up the inflammatory conditions. This study will answer the following questions: Are vaccines against the novel coronavirus less protective against Covid-19 in immune-suppressed people than in the general population? Is the duration of protection shorter in the immune-suppressed people? Does vaccination against Covid-19 increase the risk of flare-up of the inflammatory condition? We will use routinely collected anonymous information from the care of NHS patients obtained from the Clinical Practice Research Datalink (CPRD)-Aurum. CPRD-Aurum contains data on over 14 million UK residents currently registered with a GP and is linked to hospitalization and death records. We will look at data for two groups of people given the vaccine against Covid-19: Group-A: People with inflammatory conditions treated with immune-suppressing medicines, Group-B: People without inflammatory conditions and not treated with immune-suppressing medicines. Each person from group-B will be matched to one person in group-A for their age, sex, type of Covid-19 vaccine received and date of vaccination. We will follow them up using information in their electronic health records and compare their risk of hospital admission with Covid-19, GP consultation with Covid-19 and death due to Covid-19. Next, we will find out if there is a time after vaccination at which immune-suppressed people seem to stop being protected from Covid-19. Finally, we will compare the rate of getting a flare of the underlying inflammatory condition in the 6-week period after the Covid-19 vaccine to that in the remaining study period. We will involve PPI members in the study and request them to provide their perspectives before starting the study and when interpreting the study findings. They will be involved in disseminating the results and when engaging with health policy makers such as the Joint Committee on Vaccination and Immunisation (JCVI) and national specialist societies. We will share our findings with policymakers with whom we have links. Our study will inform policy around the timing of future Covid-19 booster vaccination in immune-suppressed people. We will share our results with patients and the public. We will disseminate the findings at scientific meetings and in medical journals. We will work with national charities to include key messages emerging from this study in their patient information resources.",,2023,N/A,196473.8,Human Populations | Other,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2022 +P25405,NIHR203603,Online cognitive training for people with cognitive impairment following SARS-CoV-2 infection: A randomised controlled clinical trial,"Aims: We will conduct a clinical trial to see if playing brain training games helps people who have developed memory problems following infection with Covid-19. Background: The Covid-19 pandemic has dominated our lives for the last two years. Vaccination and better treatments mean that severe infections and deaths are slowing down. However, cases of Covid-19 are still high and many people have longer term problems after they have recovered. This is called Long-Covid. Large numbers of people with Long-Covid experience problems with their brain health, such as memory problems and finding it difficult to pay attention. These symptoms could stop people getting back to work and socialising. They could even increase the risk of developing dementia later in life so it is important that we find a way to treat them. Long-Covid is affecting very large numbers of people so we need to find a treatment that works, is cheap and can be easily given to everyone who needs it. Brain training games are a good option. Our games, ReaCT, have already been proven to improve brain health in adults over 60 but they have not yet been tested in people with Long-Covid. ReaCT games are online and can be played on an app or website free of charge. Design & Methods: This will be a six-month clinical trial of the ReaCT brain training games. We will test the games in 608 people over 40, and a further 1000 people over 18, who have Long Covid and who have problems with their memory. Participants will be recruited through their GPs, publicity, social media and through a UK research study called PROTECT-UK. Participants will download the ReaCT app and will be placed in one of two groups. The ReaCT group will play the brain training games, including games that test your problem-solving and planning skills. The other group will play a simple card-matching game. We will ask participants to complete assessments of their brain health, abilities to perform daily tasks, mood and tiredness. This will tell us whether the ReaCT games improve the health of people with Long Covid. Patient & Public Involvement: This project will be guided by a group of people who have had Covid-19. They will help us to design the information for participants and decide how best to recruit people. We will also work with the PROTECT-UK research study to test the brain training app and make sure it is working properly before we start the trial. Dissemination: We will publish and present our findings for the scientific community, use publicity and social media to communicate to the public and target messages to GPs. This will make sure our research results in real improvements in people s lives.",,2024,N/A,402480,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Clinical trials for disease management | Indirect health impacts,2023 +P25406,NIHR203682,PrimaryBreathe: programme to develop and test a brief remote primary care intervention for chronic breathlessness,"Breathlessness affects the daily lives of one in ten adults, and a quarter of those aged over 70. The number of people experiencing breathlessness is growing worldwide, with increasing long-term health conditions like heart or lung disease. COVID-19 is adding to the problem, as breathlessness can continue long after initial infection. Being short of breath is disabling and frightening. Breathless people frequently contact their doctors surgery or call an ambulance. However, doctors and nurses often feel they cannot help, as breathlessness continues despite treating the underlying health condition. A small number of specialist teams have developed effective ways to support patients to improve their own breathing, without taking additional drugs. However, these teams are usually part of palliative care services and they tend to help people with severe disease, often cancer, nearing the end of life. This type of care now needs to be adapted so that it can be accessed by many more people, with any disease at any stage, and through their regular healthcare teams. This five-year research programme aims to achieve this by giving general practice staff the skills to help their breathless patients feel better, in control and out of hospital. Patients and staff are enthusiastic about this work and have been giving us advice. For example, they want treatment to be available by telephone or video, so people do not have to leave their homes. The programme will have three parts. First, the treatment, PrimaryBreathe, will be created by patients, family carers, staff and researchers working together to create a primary care version of the existing breathlessness treatment. After receiving training, primary care staff will support patients to learn techniques to self-manage their breathlessness. The treatment development process will have several stages, to make sure PrimaryBreathe meets everyone s needs and can be properly tested. Second, we will involve forty general practices from five UK regions, and over 600 patients, to test the treatment. Half the practices will be randomly chosen to provide PrimaryBreathe over four weeks, and the rest will give standard care. Patients and family carers will complete four online questionnaires over six months, measuring their symptoms and experience of caring. Third, we will generate information to support successful roll-out across UK general practices of what we found to be helpful. Patients and other experts will advise us, and we will take particular care that people from any background can receive this support. This will be the first time anyone has tried to make breathlessness support available to every person who needs it. National and international organisations are backing this work, and have agreed to help spread the findings to relieve the suffering of the increasing numbers of people living with this distressing symptom.",,2027,N/A,2806901.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25410,NIHR204435,Enabling Child and Adolescent Mental Health Services (CAMHS) to provide efficient remote treatment for child anxiety problems in the COVID-19 context,"NHS Child and Adolescent Mental Health Services (CAMHS) currently face major challenges in providing psychological treatments that (i) work when delivered remotely, and (ii) can be delivered efficiently to manage an anticipated increase in referrals as social distancing measures are relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there are concerns about likely increases in childhood anxiety as schools reopen. We worked with children, parents and NHS clinicians to develop an online program (OSI) that parents/carers of children with anxiety disorders work through with remote support from a CAMHS clinician. We will now test whether OSI works as well as what CAMHS are currently offering to help children with anxiety problems (while social distancing measures are in place and in the post COVID-19 recovery phase), and whether OSI brings wider benefits to families and CAMHS. We will also provide an understanding of parents' and clinicians' experiences of digital treatments in CAMHS in the context of COVID-19. This research has the potential to create a step change in the digital delivery of treatments in CAMHS, bringing benefits in the COVID-19 context and beyond.",,2023,N/A,280092.59,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25411,NIHR204869,Improving early warning and control of mosquito-borne disease outbreaks caused by extreme weather in Uganda,"Extreme weather such as heavy rainfall causes flooding and landslides resulting in displacement of populations and humanitarian disasters. Flooding also creates favourable conditions for proliferation of mosquitoes that transmit diseases such as malaria, Rift Valley fever (RVF) and yellow fever (YF). Flooding and landslides have become frequent occurrences in Uganda. Malaria is among the major public health problems. RVF is a viral disease that affects both livestock and humans. Yellow fever is a deadly disease that has occurred in recent years as sporadic outbreaks. These outbreaks have proven difficult to anticipate and may occur unexpectedly. We aim to improve the health system in Uganda to develop a capacity to forecast impending disease outbreaks associated with extreme weather events. We will collect data on past outbreaks and extreme weather conditions and other factors and study whether and how they were associated. We will answer questions such as how long after flooding the outbreaks of malaria, RVF and YF occurred, and the geographical proximities of affected areas. We will then develop computer models that predict the chance of disease transmission by taking into account various factors such as immunity levels in the human or livestock populations, effects of weather conditions on abundance of mosquitoes and transmission of the diseases, livestock movement patterns, and environmental characteristics. We use these models to develop an outbreak risk mapping system. We will also include a method that compares the cost-effectiveness of various courses of action to make informed decisions to prevent or mitigate the outbreaks. The research will be implemented in three phases. In Phase 1, data on past outbreaks will be analysed to determine associations with extreme weather events and other factors. Past data on disease incidence, weather variables, and other risk indicators will be used to develop forecasting models. In Phase 2, we will develop an interactive risk mapping platform based on the forecasting models and data inputs for routine use. The mapping approach will be based on a dashboard portal developed within our research partnership. In Phase 3, We will develop a national outbreak preparedness and response plan based on existing plans in close collaboration with all relevant partners. The plan will be aligned with outputs of the online portal to provide specific guidance on interventions. We will facilitate adoption and use of the outputs by engaging communities and end-users from the start and effectively disseminating the findings. We will involve affected communities, local health services, and village health workers to identify important risk factors and gaps in outbreak preparedness. We will be working closely with governmental and other partners for adoption and routine use of the system and the associated plan for prevention of outbreaks and effective mitigation of their impacts.",,2027,N/A,3492398.4,Human Populations | Environment | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Rift Valley Fever | Other,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Disease surveillance & mapping | Policy research and interventions,2024 +P25414,NIHR205699,Lungy: Development of a Smartphone-Based Breathing Management Platform with Real-time Breath Detection,"Lungy (https://www.lungy.app) is a breathing management platform that uses the smartphone camera and microphone to recognise, track and respond to breathing in real-time. It is under development for patients with breathing problems such as asthma, COPD and long-COVID. The application will encourage and guide patients through a range of relaxing breathing exercises, promoting not only breathing function but also focus, user engagement, and mindfulness. The application is intended to improve physical and mental health through regular breathing exercise. With further development, the combination of data obtained from the app could provide a plastic and hardware-free, eco-friendly alternative to traditional methods of measuring breathing function, such as spirometry used in COPD and peak flow measurements used in asthma. Lungy s underlying breath recognition technology has already been developed and validated in a proof-of-concept app for patients with stress and anxiety (and no underlying respiratory problems) with >10,000 beta testers. This project would develop the application for use in patients with breathing problems, helping to bring it to market as a medical device. Focus groups of patients with asthma and COPD will be arranged by the UK's largest breathing charities - Asthma + Lung UK - to assess the potential benefits and barriers to the adoption of a smartphone-based breathing platform. This will ensure the app remains patient-centred at every stage, informing the user interface design and future development. This would enable larger studies and leading to further funding, as well as helping to develop a powerful tool for the self-management of breathing problems.",,2024,N/A,190461.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health | Innovation,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25416,NIHR205976,Lungy: Development of a Smartphone-based Breathing Management Platform with Integrated Spirometry and Peak Flow Measurement,"Lungy (https://www.lungy.app) is a breathing management platform that uses the smartphone camera and microphone to recognise, track and respond to breathing in real-time. It is under development for patients with breathing problems such as asthma, COPD and long-COVID. The application will encourage and guide patients through a range of relaxing breathing exercises, promoting not only breathing function but also focus, user engagement, and mindfulness. The application is intended to be accessible and engaging for everyone, but also to improve both physical and mental health through regular breathing exercise. With further development, the combination of data obtained from the app could provide a plastic and hardware-free, eco-friendly alternative to traditional methods of measuring breathing function, such as the spirometry used in COPD and peak flow measurements used in asthma. Lungy s underlying breath recognition technology has already been developed and validated in a proof-of-concept app for patients with stress and anxiety (and no underlying respiratory problems) with >10,000 beta testers. This project would evaluate the feasibility of the app in measuring peak flow and spirometry, by developing new machine-learning models that run on the acquired data. Focus groups of patients with asthma and COPD will be arranged by the UK's largest breathing charities - Asthma + Lung UK - to assess the potential benefits and barriers to the adoption of a smartphone-based spirometry platform. This will ensure the app remains patient-centred at every stage, informing the user interface design and future development. If successful, this project could add new functionality to the platform, enabling larger studies and leading to further funding, as well as helping to develop a powerful tool for the self-management of breathing problems.",,2023,N/A,62462.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health | Innovation,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25419,NIHR301535,"COVID-19 survivors and kidney disease: The long term effects on kidney function, and health outcomes for people with pre-existing chronic kidney disease - a study using electronic health records","Aims of my research I aim to investigate whether people who survive COVID-19 are more likely to lose kidney function, partially or completely; I also aim to build and test a prediction tool to work out which survivors are most likely to be at longer-term risk of serious declines in kidney function. I will also be investigating the impact of COVID-19 on survivors who had kidney disease before they became unwell, and whether this increases risk of experiencing bad outcomes earlier, such as death, complete kidney failure, heart attacks, and frailty. Background When people are admitted to hospital with COVID-19, one of the common consequences is kidney injury. We are not certain why, or whether this has long-term effects in survivors, but there are strong reasons to be concerned that it may. Long-term kidney damage, known as chronic kidney disease (CKD), is associated with earlier death and heart attacks. When CKD leads to kidney failure, people require dialysis or a kidney transplant to stay alive. This has a big impact on quality and length of life, and comes at great cost to the NHS. Therefore, we need to find out what the long-term risks of COVID-19 are to kidney function, and determine who is at the greatest risk so they can be closely monitored and treated. Design and methods A way of addressing important health concerns relatively quickly is by analysing health records which cover millions of people. In the UK, we have electronically coded GP records, and for most people, we can combine these with records from hospitals. I will use these anonymised records for two study populations: Study A: I will compare risks of change in kidney function or complete kidney failure between COVID-19 survivors and people of the same age, sex, and under the same GP. Study B: Among people with pre-existing CKD, I will compare risks of death, hospital admissions, complete kidney failure, heart attacks, blood clots, low red blood cell levels, and frailty between COVID-19 survivors to people who are the same age, sex, and have the same level of pre-existing CKD. I will replicate my work with records from Sweden to understand if the findings are specific to COVID-19 or influenced by factors such as health-care system and the characteristics of the local population. I will account for many other factors like age, ethnicity, socio-economic status and pre-existing medical problems like diabetes, to establish whether our results are likely to be due to COVID-19 itself, or were due to differences in who developed severe infection. I will apply statistical modelling to records from Study A to create a straightforward tool using information like routine test results or medical history, to predict which patients are most at risk of kidney failure. I will then test this model on another large set of records from the UK and from Sweden to ensure that it is reliable. Patient and public involvement My ideas have been informed by meetings including patients, and several patients are keen to join my advisory panel. I will ensure this includes COVID-19 survivors with and without CKD, and a member of public who has not had COVID-19. We will meet at the start of my research to finalise plans, and then I will update them of my progress every six months. I will seek their advice on how to ensure my findings reach other patients and the public. Dissemination Because this is a big, important study, I will share findings with the media, charities, healthcare professionals, and policy makers to ensure that it has maximum benefit for patients.",,2024,N/A,689641.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25421,NIHR301784,'ÄúIntegrating public health with high street revitalisation: A mixed methods analysis of local initiatives addressing the food environment'Äù,"Background Unhealthy diets are amongst the greatest contributors to disease in England. Eating an unhealthy diet does not only depend on individual choices but also on the availability, accessibility and affordability of (un)healthy food and beverages. In England, people living in economically deprived areas are more greatly exposed to unhealthy food, and the associated harms. Public health measures have increasingly focused on promoting health by changing the types of food sold on high streets. This strategy is controversial as it often involves attempting to balance public health goals with objectives to support local economies. Furthermore, the involvement of business representatives in local authority decision-making may lead to public health objectives being over-ridden by competing, profit-driven, interests. A study that examines the compatibility of public health and economic goals for local high street policies is particularly timely given the restrictions imposed in response to the COVID-19 pandemic, which have disproportionally affected high street businesses. Now that economic recovery is high on the political agenda, it is especially important to ensure that efforts to revitalise high streets do not overshadow public health goals, and negatively affect population health and healthcare services in the long term. In order to support local governments in their efforts to integrate public health with economic goals, more research is needed on: How public health objectives can be achieved and prioritised in the context of increased incentives to support the local high streets, and How local government can engage with business and other stakeholders to foster healthier environments. Project aims This project aims to investigate the integration of public health objectives with efforts to revitalise high streets in England, and to explore the priorities and influence of different public, private and other stakeholders in decision-making about the local retail environment. Methods The project aims will be addressed by four research components: A review of the existing evidence on the public health impact of initiatives to revitalise high streets, and the ways in which these initiatives are believed to promote or hinder health. An analysis of how different stakeholders in England describe and justify different approaches to supporting and regulating high streets. This analysis will assess how prominently public health features in the framing used by different stakeholders. A qualitative comparative case study analysis of the Childhood Obesity Trailblazer programme, currently being implemented in five English local authorities. The Trailblazer programme is a good example of a public health initiative that works with policymakers in all government sectors, businesses representatives and other stakeholders to promote healthier food retail environments and improve public health. I will collaborate with the involved local authorities to explore their objectives and activities surrounding the revitalisation of the (food) retail environment, and how the Childhood Obesity Trailblazer initiatives are prioritised and integrated with these objectives. I will also examine how business representatives, voluntary organisations and community members engage with the programme. The synthesis of all research findings to identify what helps and hinders local authorities in ensuring that support for local economies does not overshadow public health priorities. I will develop accessible guidance and research summaries for policymakers and community members, in collaboration with people from those sectors. Members of the public will be involved throughout the research project to ensure that the research objectives and activities are relevant to the concerns and priorities of the public in England. Public collaborators will also be involved in the dissemination of findings, ensuring that they become available to local governments and interested members of the public. This will be done through presentations, a briefing document, web resources and freely accessible publications.",,2024,N/A,372937.5,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2022 +P25425,NIHR302287,"Using routinely collected hospital data to investigate the impacts of static and dynamic treatment regimes, with an application to ventilation strategies for COVID-19 patients","Over 470,000 people have been hospitalised due to COVID-19 in the UK to date. 36,000 of those required intensive care, of which the majority received breathing support, known as ventilation. Ventilation can be 'invasive' or 'non-invasive'. Invasive ventilation is where a machine does the breathing for a patient, who must be sedated and have a breathing tube put into their windpipe. Non-invasive ventilation is where a patient receives air and oxygen via a tightly-fitting mask at high pressure. Around 40% of COVID-19 patients admitted to intensive care have received invasive ventilation, however, there is debate over whether and when to introduce invasive ventilation in COVID-19 patients. The ideal way to study whether one treatment is more effective than another is through a randomised controlled trial (RCT). This involves randomly choosing half of a group of patients to receive one treatment and half to receive another, enabling a fair comparison between treatments. However, RCTs are limited because they are generally not designed to look at multiple treatments or treatments that vary over time. Furthermore, RCTs may not be possible due to financial, logistical or ethical constraints. Meanwhile, there is a growing availability of 'observational' data routinely collected when patients are admitted to hospital or attend their GP, known as electronic health records. These data are often available on a large number of people and reflect how treatments are used in day-to-day care, providing a useful resource for examining the effects of different treatments. Using such data has challenges as the treatments are not randomly allocated. The data have complicated features that must be dealt with using tailored statistical methods, and in recent years there have been many advances in such methods. In this fellowship I will use and compare existing statistical methods and develop new methods to evaluate the effects of treatments using routinely collected data. I will focus on two key statistical challenges. First, the fact that measurements on patients' clinical status are collected at irregular time intervals, and on differing schedules for each patient. This presents a challenge as most of the statistical methods assume measurements are made at regular time intervals. Second, we may want to examine the effects of both 'dynamic' and 'static' treatment strategies. A 'static' treatment strategy is where the treatment received is the same for all patients meeting defined criteria, e.g. 'all patients receive invasive ventilation within 24 hours of admission'. A 'dynamic' treatment strategy is where there are rules that adapt the treatment to the current status of the patient, e.g. 'transfer patient from non-invasive to invasive ventilation when breathing rate exceeds X'. It is more complicated to evaluate dynamic treatment strategies. I will apply the methods identified to investigate the impact of invasive vs non-invasive ventilation on outcomes of patients with COVID-19. I will (i) compare the impact of invasive vs non-invasive ventilation ('static treatment strategy') and (ii) identify if and when patients should be transferred from non-invasive to invasive ventilation based on their current status ('dynamic treatment strategy'). The data source is routinely collected hospital data of all patients with COVID-19 admitted to University College London Hospital since January 2020. I will seek involvement from patients who have experienced critical illness and ventilation to understand their experiences and what outcomes are important to them, and to seek advice on communicating the outcomes of my research. This work will give patients, doctors and policymakers more information about ventilation strategies, allowing them to make more informed decisions about the best ventilation strategy tailored to the patient. It will impact future research by providing methods that enable best use of routinely collected hospital data.",,2025,N/A,411051.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25426,NIHR302338,Mapping patterns of viral load emission in exhaled breath over the course of acute respiratory virus infections,"Background Respiratory virus infections can cause significant problems for infected patients, the economy and the NHS. The most profound example of this is the COVID-19 pandemic, but seasonal flu and other viruses also exist. In older frail patients, such infections can be fatal. The diagnosis of respiratory virus infections is by a swab in the back of the throat and nose (nasopharyngeal swab). However, this can be very uncomfortable - and although it can help a doctor diagnose whether someone has a respiratory virus infection, it doesn't necessarily tell us whether that person is contagious to others. This is likely because most people who get exposed to an infected person are not exposed to the virus in their throat, but by the virus that they breathe out. In fact, many patients who are positive for SARS-CoV-2 on the nasopharyngeal swab are not contagious to others if they are already several days into their illness. Study aims I have supported the development of a method to sample virus that is breathed out by infected patients, by using harmless strips that are placed on the inside of routinely used duckbilled-shaped facemasks. These strips are able to quantify the amount of virus that someone breathes out over time. We have recently shown that this mask based sampling system is able to detect SARS-CoV-2 virus in infected patients. The aim of this PhD fellowship is see whether the amount of virus detected time on the facemask is different to that detected by the nasopharyngeal swab. Ultimately, the mask could be a more accurate marker of individual contagiousness than the nasopharyngeal swab. If this is the case, it could be of immediate public health benefit, allowing infectious patients to be isolated before they are symptomatic; allowing non-contagious patients to be discharged to a nursing home in a timely fashion without worry of transmission to other residents; as well as allowing non-contagious persons to go to work or travel abroad. Methods There are three work packages (WP) of this fellowship: Work package 1: To systematically review existing methods of sampling the breath for bacteria and viruses Work package 2: To sample 100 study participants and one member of each of their households using the masks with the special strips inside and the nasopharyngeal swabs. Each study participant will provide five masks and swab samples over two weeks. The design of this study will form the basis for future bigger studies and will see if there are any problems with patients wearing the masks; how many patients can we get at different stages of infection; if patients can be followed up successfully; what measures might work well for future, larger studies. Study participants will also fill out a symptom diary, grading their symptoms on a daily basis and a brief questionnaire detailing their basic demographic details (age, sex, ethnicity etc). Work package 3: Use mathematical modelling methods to try and map out quantities of virus throughout the first two weeks of illness based on WP2 data. Patient and public involvement (PPI) PPI has been in place since the study was conceived and will continue throughout the project. I sought the opinion of ten PPI representatives, all of whom thought the work was important and will form a project group that will meet bi-annually to discuss study results. Dissemination of findings Results will be shared with participants and the public through the involvement of PPI representatives; presented at academic conferences and published in high impact journals.",,2025,N/A,527994.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease transmission dynamics",2022 +P25429,NIHR302902,"Adapting the Fibromyalgia self-management programme to develop an online support package, optimising engagement and uptake of the intervention.","Introduction Fibromyalgia (FM) is a long-term condition that causes pain and fatigue. The condition is common, and estimates suggest it affects approximately 5% of the population. FM is more common in females and is associated with various health conditions. Unfortunately, the cause of FM is poorly understood, and as a result, diagnosing and treating the condition can be challenging. The treatment of FM includes both medicines and other non-medicine-based interventions, and current guidelines suggest that exercise and self-management strategies should be used in the first instance. The Fibromyalgia Self-Management Programme (FSMP) is a clinically developed exercise and education group intervention. The programme aims to provide FM-specific education and exercise advice and support the skills to self-manage. Currently, the FSMP is delivered by a team of specialist Rheumatology Occupational Therapists (OTs) and Physiotherapists (PTs) in Bath and a Community Therapy team in Southampton. Traditionally, the FSMP has been delivered face-to-face, but since the COVID-19 pandemic, the clinical teams have adapted the FSMP to enable virtual delivery and now offer both a virtual and face-to-face programme. However, the supporting information has not been adapted for online use. The study aims to develop an online resource to support the FSMP in the NHS so it can be delivered virtually, face-to-face or independently. I plan to ask adults with FM what information is needed to develop this resource, and then it will be tested to see if it works in clinical practice. Design and methods There are three work packages in the study. In work package one (WP1), I will explore what adults with FM would like from an online resource. To do this, I will summarise the evidence in the literature on existing online self-management programmes for FM. Then, I will conduct several focus groups with adults living with FM and the therapists delivering the FSMP. These focus groups will explore the information adults with FM need to manage FM successfully, how they might like to use the information provided in the FSMP, and the online features that would help support the delivery of the programme. Finally, at the end of WP1, I will work with a web development team to create an online FSMP resource. In work package two (WP2), I will ask people living with FM to use the online FSMP resource to see what works well and needs improvement. To do this, I will conduct a series of interviews with people about their views and experiences while using it. These interviews will help the web development team refine the online resource until it is ready to be tested. Finally, the online FSMP resource will be tested in work package three (WP3). Adults living FM who are referred to Bath or Southampton FSMP will be invited to use the online resource while attending the programme. I will also invite adults living with FM to use it independently without input from the therapy team. Once completed, I will explore both participants' and clinicians' experiences of using it. Information gathered in WP3 will help design a future research study. Patient and Public Involvement (PPI) People living with FM have assisted with the development of this research application. I will consult PPI representatives throughout the study for the planned research and seek advice regarding recruitment, development of topic guides, interviews and focus groups, and how the findings can be used in clinical practice. Conclusion This research will mean clinicians can offer adults living with FM an online resource to support the delivery of the FSMP in the NHS. Findings from the research will help design a future study testing effectiveness.",,2026,N/A,411733.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research","Supportive care, processes of care and management | Indirect health impacts | Health service delivery",2023 +P25430,NIHR302904,"Improving the lives of people living with chronic breathlessness due to advance disease via a self-guided, internet-based breathlessness supportive intervention SELF-BREATHE","Background Some health conditions make breathing difficult and uncomfortable. When this happens every day, it is called chronic breathlessness. Over 3 million people living with heart and lung disease have chronic breathlessness in the UK. In addition, people living with long COVID commonly have breathlessness and they struggle to manage it. Breathlessness is very difficult for patients themselves and their families, resulting in disability and feelings of fear, distress, and isolation. Due a to lack of supportive breathlessness services many patients frequently attend hospital Accident and Emergency (A&E) departments seeking help. Given the on-going challenges faced by the NHS such as long waiting times, staff shortages, increased demand for services because of the COVID-19 pandemic, there is an urgent need to develop new ways to support those living with chronic breathlessness. One potential solution is to offer support online as in the UK, 7 out of every 10 people with chronic breathlessness are internet users. With the help of patients and NIHR funding I developed an online breathlessness supportive website called SELF-BREATHE. SELF-BREATHE provides information and self-management tools such as breathing exercises, that patients can do at home themselves. I have tested SELF-BREATHE as part of its development and it is acceptable and valued by patients. But what is unknown is whether SELF-BREATHE improves patients' breathlessness and their life? This is the question my research seeks to answer. Aims 1. To test if using SELF-BREATHE for six-weeks improves patients' breathlessness, their quality of life and whether SELF-BREATHE should be offered within the NHS 2. To see if patients opt to continue to use SELF-BREATHE after six-weeks and what benefits this may have for patients. Methods I will carry out a randomised controlled trial. For this, 246 people living with chronic breathlessness will be recruited. Each person will be randomly chosen by a computer to get their usual care or usual care plus access to SELF-BREATHE. All study participants will complete questionnaires at the start of the study, thereafter at six weeks and six months. These questionnaires will ask patients about 1) their breathlessness and its effect on their life and 2) planned and unplanned hospital visits. At the end of the study, I will compare answers to these questionnaires between the two groups at six weeks and six months. This will tell if SELF-BREATHE improved patients' breathlessness and reduced their need for unplanned hospital visits e.g., A&E attendances due to breathlessness. Patient and public involvement (PPI) I have, and will continue to, actively work with PPI groups. This includes PPI groups within the Cicely Saunders Institute, Asthma and Lung UK, NIHR-Research Design Service- London and the Centre for Ethnic Health Research. PPI input to date includes development and early testing work of SELF-BREATHE and the writing of this application. PPI expertise has ensured the project is focused on what matters to them. PPI members will advise on study promotion, patient recruitment and develop trial resources (e.g., information sheets, recruitment posters). PPI members will be paid for their time. Dissemination Once the study ends, I will share the findings through journal articles for researchers and professionals, via patient facing websites and social media. I will hold a knowledge exchange event, bringing together patients, carers, health professionals and health service planners to reflect on the study results.",,2028,N/A,1726283.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research | Clinical characterisation and management",Indirect health impacts | Health service delivery | Post acute and long term health consequences,2023 +P25431,NIHR302958,Fostering tEAmwork for ResiLiEnt Staff and Safe care: driving post-pandemic recovery and renewal in Intensive Care Units (FEARLESS ICU),"The problem Intensive care units (ICUs) post-pandemic are facing a staffing crisis. ICUs have always been scary environments in which to receive/deliver healthcare, but COVID19 introduced added anxiety among overworked staff, and concerned patients/family members. Stretching ICU capacity over a prolonged period, to manage increased demand, meant changes in usual ways of working with staff taking on additional roles and responsibilities in newly-formed teams alongside redeployed or inexperienced staff. Many patients sadly did not recover, new care routines and therapies were introduced rapidly, while visiting restrictions limited staff access to patients' health histories and care preferences. Research interviews I completed with staff and families throughout the pandemic revealed staff to be under enormous pressure, which increases the risk of errors and omissions. Prolonged exposure to such working conditions place staff at high risk of ill health, leading many to consider resigning. Family members have also felt excluded from the care decisions, lacking contact with their loved ones' care providers. These changes are not reverting but gradually becoming the norm. The opportunity ICU staff have shown remarkable resilience in responding to the increased physical and psychological demands placed on them, enabled through unprecedented levels of camaraderie and teamwork. High levels of teamwork have long been shown to have a protective effect, with ICU research linking these to better outcomes for patients, including reduced mortality; higher family satisfaction; and improved staff wellbeing. However, with ICUs remaining busy due to the inevitable backlog and ongoing viral outbursts there are increasing signs, such as from the NHS staff survey, that these high levels of teamwork are waning. This is worrying given the UK Intensive Care Society reports an unprecedented shortage of ICU staff and expects demand for ICU beds to remain high as a recurring feature of COVID19 becoming endemic, with increased/stretched capacity each time to be sustained for months. Fostering high levels of teamwork could drive staff resilience while engendering patient safety; but, more evidence is needed about the changing nature of teamwork in ICU to inform interventions that can improve recovery and renewal. Method This research will complete a detailed analysis of current teamwork practice in ICUs across the UK, identify examples of strong and challenged teamwork practice, and understand the factors that influence team working in the post-pandemic context. This will be achieved by analysing new and historical NHS staff survey data to identify high-level trends on organisational, professional group, and staff profile related factors that influence teamwork. These trends will inform and complement in-depth work with staff on the ICU frontline, involving observations of actual ICU working and interviews with a range of staff of different seniority and from different professions, experienced or new in ICU. I will then use different examples from practice in reflective workshops with ICU teams and guide them to identify ways teamwork can be developed and sustained. As a result, I will develop a blueprint, a logic model and toolkit (including a website, videos, diagnostic tools, training material and exercises) for improving ICU teamwork practice; which I will implement and evaluate in successive research. Impact Project outputs will be disseminated widely through videos, blogs, a project website and newsletter; as well as policy briefs, news pieces, conference presentations and academic publications; and, a final project multi-stakeholder symposium bringing together clinicians, service users and policy makers. By generating an in-depth, evidence-based understanding of teamwork in ICU, and offering a toolkit to ICU teams across the NHS, the project can have a direct impact on the teamwork practice of ICU staff, improvement of which has long been linked with better patient, staff and organisational outcomes.",,2027,N/A,995112.31,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Health Systems Research,Health workforce,2023 +P25432,NIHR303007,Accounting for the impact of the Covid-19 pandemic on routine data resources: development and application of novel methodology for the analysis and reporting of population-based cancer statistics,"Aims of the research The aims of the project are: O1. To assess the overall impact of the COVID-19 pandemic on: the timing and stage of cancer diagnoses; treatment allocation for cancer patients; and non-cancer death rates in the general population. O2. To ensure that we can fairly compare and monitor cancer survival and incidence over periods of time including years during or following the pandemic. O3. To make sure that research studies that rely on routine data resources can continue to make fair comparisons despite the impact of the pandemic. O4. To communicate cancer survival statistics in a patient-focussed and meaningful manner. Background to the research Monitoring the number of cancer cases and patient survival is vital. This information is used in the planning and delivery of health services, and in the evaluation of diagnostics and treatment at the population level. Comparisons are made between risk factor groups such as age, deprivation, sex, regions/countries and stage. These comparisons help to identify groups to target with the aim of reducing differences in incidence and survival. During the pandemic routine delivery of the health service was severely disrupted, as cancer screening services were paused, the availability of GPs, oncologists and other healthcare providers was reduced, and there were delays to accessing cancer treatments. Similar impacts were seen across many disease areas including cardiovascular disease, kidney disease and diabetes. As a result, there have been large changes to the data due to potentially worse cancer survival and increased non-cancer death rates in the general population. These population death rates, which have been increased due to Covid-19, are needed to estimate common cancer survival measures. Ignoring these changes can result in bias and excluding affected data is wasteful. Hence, it is important to develop statistical methods to ensure we make best use of the data. Design and methods used To address the aims, I will apply the following methods: M1. I will search for previously published research regarding the scale of the impact of the pandemic on cancer-related clinical practice and routine data resources. I will conduct simulation studies to scope the impact of these changes on cancer survival. I will investigate the impact of the reduced cancer diagnosis services. M2. I will evaluate methods to adjust for the decrease in reported cancer cases to fairly report survival metrics. I will develop approaches to alter population-mortality files to enable the estimation of unbiased cancer survival metrics. M3. I will develop methods to quantify the contribution of a) delayed diagnosis b) suboptimal treatment and c) varying competing mortality on cancer survival. M4. I will develop two interactive webtools: one to provide patient-focussed metrics of cancer survival for a range of cancer types and one for researchers to illustrate the sensitivity analysis. I will develop a workshop to disseminate the findings of this project. Patient/service user, carer and public involvement I have identified a National Cancer Research Institute (NCRI) PPI representative to be named PPI advisory group lead. This patient has been involved in the development of this project through review of this plain English summary, and the scientific abstract. I will approach further patients to form the remainder of the advisory group. We will continue discussions regarding patients' experiences of cancer diagnosis and treatment during the Covid-19 pandemic, and any concerns they may have to further shape the project. Dissemination I will disseminate my findings from this project by publishing my work in journals and presenting at international conferences. I will develop a dissemination workshop and two webtools, one patient-focussed and the other researcher-focussed, to improve the communication of reported cancer survival metrics.",,2026,N/A,364687.5,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Not applicable,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Communication | Indirect health impacts | Health information systems,2023 +P25434,COV0143,"Developing and Delivering targeted SARS-CoV-2(COVID-19) health interventions to Black, Asian and Minority Ethnic (BAME) communities living in the UK","COVID-19 pandemic appears to cruelly discriminate, inflicting a disproportionate burden of illness and death across Black and South Asian communities. There are concerns that unless targeted interventions are delivered the current pandemic will only serve to magnify existing social inequalities experienced by UK BAME communities. The research team has extensive experience in co-producing digital interventions to assist BAME communities to navigate barriers and gain equal access to care. The current project aims to (a) design culturally specific health messages for Black and South Asian groups and (b) deliver these messages through specific trusted communication channels, in order to have the needed impact on behaviour change and reduce COVID-19 risk, targeting the following: risk and susceptibility, proximity and social distancing and infection control, highlighted by our public and patient involvement. With the support of the local and regional BAME community groups, knowledge champions (community and faith leaders) and knowledge advocates (from public health and allied health professionals), we will co-produce key written/visual documents, short films up to 2 minutes (mainly for smart phone viewing) and mobile apps. The specific content of the messages will be a combination of public health advice and targeted, salient and culturally appropriate messages. We will evaluate the efficacy of our interventions. We will disseminate, share information and experience gained in a rapid and timely manner to support the behavioural change to mitigate the risk of infection by engaging with stakeholders, community leaders, policy makers, including NHS England and PHE.",,2022,N/A,673371.6,Human Populations,Black | Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2020 +P25435,COV0254,"Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: the COVID-HEART study","COVID-HEART is a large UK multi-centre consortium committed to work together to answer a set of unique and important clinical questions. The bid is backed by the major UK professional cardiovascular societies and the NIHR-BHF Cardiovascular Partnership have designated it as a ""COVID-19 Cardiovascular Disease UK Flagship Project"" (see attached letter). Whilst up to 20% of hospitalised COVID-19 patients may have cardiac injury based on serum troponin (and associated with high mortality), this is non-specific and can relate to pericarditis, myocarditis, acute coronary syndromes, acute heart failure, arrhythmias, or simply hypoxia/sepsis/shock. Cardiovascular magnetic resonance (CMR) can make a specific diagnosis and is recommended in European Society of Cardiology practice guidelines. We will use CMR to determine 1) the UK prevalence of acute myocardial injury/myocarditis secondary to COVID-19 and the severity of presentation; 2) how clinical outcomes associate with recognised risk factors for mortality such as age, sex, ethnicity and comorbidities (diabetes, hypertension, heart failure, and coronary/peripheral vascular disease; 3) if there are differences in myocardial recovery at 6 months dependent on demographics, genetics and comorbidities, and how this impacts on patient quality of life and functional capacity; 4) if we can improve the ECG diagnosis of myocarditis minimising the requirement for invasive cardiac investigations. Ethics approval has been granted for clinical CMR scans enabling us to start quickly, and if funded we would extend this approval to include the additional research scans, other investigations, patient reported outcome measures and follow-up as described below.",,2021,N/A,1023125.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P25436,COV0416,Development and manufacture of an improved replication-deficient simian adenoviral vector to prevent COVID-20,"The University of Oxford and Vaccitech jointly developed and then exclusively out- licensed a serogroup E chimpanzee adenoviral vector vaccine encoding the SARS-CoV-2 spike glycoprotein to AstraZeneca. This vaccine, ChAdOx1 nCoV-19, given as a single dose, has moved into Phase 2/3 studies in the UK, and in August 2020 begins Phase 3 studies in the US and Brazil. There are concerns that anti-vector immunity to the ChAdOx1 backbone may limit early boosting responses, or even boosts given on a yearly basis. Vaccitech has developed an alternative serogroup C chimeric gorilla adenoviral vector vaccine (""GAdVac""), which has been shown in completed murine studies to elicit higher antibody and T cell immune responses than the ChAdOx1 candidates. Vaccitech is now developing the full-length spike glycoprotein encoding GAdVac candidate and will use this as both a stand-alone vaccine and evaluate the use of this candidate as a prime and a boost for the ChAdOx1 platform. Efficacy studies in ferrets will be pursued with Public Health England at Porton Down. The pre-master virus seed will be produced in the SOP- controlled Early Development Laboratories at Vaccitech in Oxford, and then transferred to Advent (Rome, Italy) for GMP manufacture. Advent has successfully made three GMP released lots of ChAdOx1 vectors for Vaccitech. Scientific advice will be sought from MHRA, and a formal GLP toxicology study will be performed due to the novelty of this vector. Within 12 months, the CTA to begin a Phase 1 immunogenicity study will be complete.",,2020,N/A,205694.28,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,"Clinical Trial, Phase I",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Pre-clinical studies | Phase 1 clinical trial,2020 +P25437,Covid-19 - REMAP-CAP,"REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform trial for Community- Acquired Pneumonia (COVID-19)","REMAP-CAP is a randomised clinical trial, which has been specifically designed to be able to adapt in the event of a pandemic. Prior to COVID-19 REMAP-CAP was running in 12 countries worldwide and was recruiting patients admitted to an intensive care unit (ICU) with pneumonia which had developed in the community. Since the COVID-19 pandemic, REMAP-CAP has used its novel design, which enables it to adapt, to change to evaluate the most relevant treatment options in patients admitted to an ICU with severe COVID-19. This change includes, evaluating both new and existing interventions targeted at patients with COVID-19, and using different clinical outcomes to obtain an answer quicker. The design of REMAP-CAP allows it to assess different types of treatment at the same time to understand which are the best treatment strategies. The original treatment types being tested in REMAP-CAP are: 1) use of COVID-19 antiviral medication; 2) use of COVID-19 immune modulation; 3) choice of antibiotic; 4) duration of macrolide treatment; and 5) steroid treatment. REMAP-CAP also uses the results within the trial to allocate more patients to interventions that are more likely to be effective and can provide an efficient way of generating time-critical evidence to improve patient outcomes during a global pandemic.",,2023,N/A,1549541.2,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation | Clinical characterisation and management",Clinical trials for disease management,2020 +P25438,COVID19 ImperialVacc,saRNA COVID-19 Vaccine Clinical Trial,"A vaccine is critical to tackling coronavirus. The clinical and scientific communities are increasingly of the view that whilst isolation, social distancing and testing can get the world through the current coronavirus problem, the only long-term solution to beating the disease will be finding a vaccine. To find a successful vaccine will take the collective effort of government, academia, industry and healthcare. We know that traditionally vaccine development can take years and we also know more fail than succeed. To accelerate development, government will have a key role to play in derisking projects, by funding their early stage R&D and clinical trialling, and in corralling industry to make sure we have the manufacturing capacity and effective supply chains to produce vaccines at scale, quickly. This is likely to mean manufacturing at risk, i.e. investing in facilities now and producing millions of doses of vaccines ready for deployment, which may turn out not to work. Government has already taken action to bring together all those working on a vaccine in the UK. A Vaccines Taskforce has been set up reporting to the BEIS and DHSC Secretaries of State, as well as to Sir Patrick Vallance and Jonathan Van Tam. The taskforce is bringing together government, industry, academics, funders, regulators, logistics and finance to make rapid decisions that will accelerate progress on the development of a Covid-19 vaccine and vaccinate the right proportion of the population as soon as possible after a vaccine is available. For the UK to be in a position to vaccinate the right proportion of the population as soon as possible after a vaccine is available, we need to: ? Support discovery, development and scale up in the UK; ? Prepare the UK to offer itself as an expert clinical testing site and possible manufacturing site, proactively approaching companies such as Moderna which are at the forefront of vaccine development; ? Review regulations to facilitate rapid, well supervised trials; ? Develop funding and operational plan for procurement and delivery of vaccines and; ? Build on the UK s R&D expertise to support the international effort. On the first of those priorities, there are 41 leading vaccine candidates in the world, of which the UK is home to two: at Oxford University and at Imperial College. A team at Imperial College London, led by Robin Shattock, have been developing a saRNA vaccine for COVID-19, that aims to cut half a billion off development costs, and years from the traditional cycle, potentially allowing the UK to begin immunisation in late 2020. The outlined plan assumes that vaccine production will be started at risk, based on early positive signs from the Phase 2 clinical trials. This is necessary in order to move into immunising the population ahead of the coming winter.",,2022,N/A,3940360,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,"Vaccines research, development and implementation",,2020 +P25439,COV-LT-0022,Non-hospitalised Children & young people (CYP) with Long Covid (The CLoCk Study),"aim(s) of the research: It seems that some children and young people (CYP) remain ill for a long time after infection with COVID virus. They are said to have long COVID . Something similar can follow a common childhood infection called glandular fever. Doctors don t know how to diagnose long COVID, how common it is or how long it goes on for. There is no simple test for long COVID. We need to know more about it if we want to treat it. background to the research: Little is known about long COVID in adults or CYP. Risk factors for worse COVID in CYP include obesity, pre-existing diseases, learning disabilities, diseases of the brain, mental health problems and coming from an ethnic minority. The CYP likely to be most at risk of long COVID are teenagers who are more at risk of persistent fatigue and mental health problems after other viral infections. design and methods used: We will approach 30,000 CYP, half of whom we know had COVID. We expect 6,000 to agree to help us and we will ask them whether they still have physical or mental problems at 3, 6,12 and 24 months afterwards. We can compare the 3,000 responders who had a positive COVID test with the 3,000 responders who didn t test positive. We can then agree on what is a medical diagnosis of long COVID and how we might treat it. patient and public involvement: (PPI): We will have a paid PPI lead who will ensure co-production with carers and CYP. We will also use some funds to encourage busy carers and CYP to give their valuable time to complete the surveys. Complete transparency: We will share all our results ASAP for free with anyone who wants to see them, especially the CYP who take part.",,2024,N/A,2580529.62,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25440,COV-LT2-0010,Using Activity Tracking and Just-In-Time Messaging to Improve Adaptive Pacing: A Pragmatic Randomised Control Trial,"Long-COVID symptoms change regularly, often getting worse after activity. Adaptive pacing (AP) is a way for people who experience these symptoms to better manage their day-to-day activity. AP needs people to continuously track their daily activities and balance what they plan to do with how much energy they feel they have. However, this is not always easy because the amount of activity that will cause symptoms to get worse is different for everyone. Also, individuals must keep track of their activity (perhaps for several days) which can also be challenging, particularly if poor memory is a symptom. With help from people with long-COVID, we have designed a project to make AP easier for people with long-COVID to use. We will track activity for them and send alerts if they risk doing too much. The aim is to help individuals better plan their day-to-day activities and prevent periods where symptoms become worse. We will recruit two groups; one will follow the standard AP advice, and the other will try our modified AP approach. We will ask this group to wear a Fitbit activity monitor and download a mobile phone app designed by us. We will use the information from the Fitbit to keep track of each participants activity level. We will then send alert messages if it looks like they might do too much. This way, each person has their own AP plan. The activity and messaging support will last for three months. Afterwards, we will review how effective it was by comparing them to the usual care group. If this approach works, we will see if the tracking and messages can be improved and offer this to the control group so they can also benefit. We will also look for ways to scale up the process to help more people.",,2024,N/A,678283.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25441,COV-LT2-0059,ReDIRECT: Remote Diet Intervention to REduce long Covid symptoms Trial,"WHY THIS RESEARCH IS IMPORTANT Around 10% of people infected with COVID-19 have symptoms for 12 weeks or longer (Long COVID). People with Long COVID also have overweight/obesity to a similar extent than the rest of the population (~70%), which may worsen their symptoms. Weight management programmes in adults with overweight /obesity can reduce symptoms such as fatigue, breathlessness and pains, also common with Long COVID. However, we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported entirely remotely, in people with Long COVID. OUR PLAN 1. We will adapt an established weight management programme and its evaluation for people with Long COVID, through stakeholder workshops with patients, carers and staff. 2. A trial will be conducted with 200 people with Long COVID, identified through their GP, patient groups or social media. We will allocate 100 individuals to receive the personalised, professionally-supported weight management programme, 100 to usual care, and compare Long COVID symptoms, weight loss, quality of life and value for money after 6 months. After 6 months, the intervention will be provided for the control group. Experiences will be documented for 12 months. INVOLVEMENT OF PATIENTS AND STAKEHOLDERS People with Long COVID have been involved extensively in developing this project. Their priorities are to reduce symptoms like fatigue, breathlessness and pain. They are keen to explore if effective weight management would help their symptoms and overall functioning, especially a programme that can be followed remotely from home. A group of patients and other stakeholders will provide advice throughout the project. SHARING OUR FINDINGS We will use our relationships with patient organisations, stakeholders and the research community to share findings using traditional and social media.",,2024,N/A,1538994.8,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Post acute and long term health consequences | Community engagement",2021 +P25442,COV-LT2-0072,Long COVID Core Outcome Set (LC-COS) project,"This study aims to reach an agreement amongst researchers, clinicians, patients and people from other key perspectives ( stakeholders ) on how to measure improvement in Long COVID. This is particularly important for studies of whether treatments work ( treatment trials ) where using different measurement methods makes it difficult to compare results from different studies. It is also important that clinicians treating Long COVID measure aspects of disorders that matter most to patients, health professionals and others (for example those funding services). Researchers aim for such agreement by developing Core Outcome Sets (known as a COS ) which specify the core (i.e., key things) that should be measured in all patients. The ideal way to reach agreement on ""what to measure?"", and ""how to measure?"", has been defined by the COMET (Core Outcome Measures in Effectiveness Trials) framework which we will use to assemble global experts from relevant areas of research and medicine to work with patients and other stakeholders to compare and then reach agreement. The initial work on ""what to measure?"" is already underway and will be completed by the start of this study. This study aims to get agreement on ""how to measure?"" these core outcomes in terms of what are the ideal questionnaires or other assessment methods. Once agreed the COS will be widely disseminated by publications in the peer-reviewed scientific journals and via network members as well as the leading national and international organisations. We will ensure that mainstream and social media are informed of the COS increasing awareness in healthcare professionals, researchers, Long COVID patients and the public. Our team has established strong links and is working with key national and international groups (e.g. UK research and clinician networks and the World Health Organisation) to maximise the impact of this work improving how we measure Long COVID.",,2023,N/A,239799,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Data Management and Data Sharing,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P25445,NIHR130808,The health and health inequalities impact of a place-based community wealth Initiative,"Background: The large regional economic disparities in the UK lead to some of the largest regional differences in health of any country in Europe. It is likely that the current COVID19 pandemic will exacerbate these economic and health inequalities. Previous attempts to address this issue have had limited success. Intervention: The Community Wealth Initiative (CWI) aims to address this problem in Preston. It involves a coalition of large employers coordinating action to improve the local economy and reduce inequalities by: (1) changing procurement to support local supply chains; (2) supporting local small enterprises (cooperatives, social enterprises, charities, small businesses); (3) investing pension funds in affordable housing; (4) improving working conditions and (5) renovating empty properties for social housing. This strategy has the potential to improve health, reduce health inequalities and make Preston more resilient to the adverse consequences of the COVID19 pandemic. Objectives: 1) Investigate the impact of the Preston CWI on social, economic and health outcomes, and assess whether the Preston CWI has mitigated the impact of the COVID19 pandemic on these outcomes. 2) Assess additional costs associated with implementing the CWI though changes in procurement practices and whether these costs outweigh the benefits. 3) Increase our understanding of the process of change within Preston initiated by the CWI and the pathways to changes in outcomes. 4) To draw out policy, practice and research implications for future CWIs so that they maximise their health and wellbeing benefits. Methods: We combine two approaches to achieve these objectives. Firstly we estimate the impact of the CWI on our primary outcome 'Äì the Small Area Mental Health Index, by using propensity scores to match areas in Preston with a set of comparison areas that have similar characteristics but have not implemented a CWI. We will then apply difference-in-differences analysis to compare changes in this outcome in Preston before and after the intervention with changes in the outcome in comparison areas. We will use similar methods to assess the impact of the CWI on investment, employment, wages and life satisfaction. We will assess whether the intervention mitigated some of the adverse effects of the COVID19 crisis and evaluate additional financial costs from changes in procurement practice. Secondly we use a combination of participatory network analysis, interview, observation and documentary analysis to understand the process of change that has taken place in Preston and what has helped or hindered this. Timeline for Delivery: The research will be delivered between April 2021 and Sept 2023. Anticipated impact: The research will indicate the critical components needed for implementing CWI and the likely costs and benefits of these approaches. We will work with local governments across the UK through the Community Wealth Building Centre of Excellence, to implement these findings in developing local economic strategies that are likely to improve health and reduce health inequalities.",,2024,N/A,825574.65,Human Populations | Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2021 +P25448,NIHR132733,Research-informed decision-making: learning from each other to develop research capacity and activity within South Tyneside Council whilst harnessing the benefits of a wider regional research support infrastructure,"Research Question: Why, what, how, who, when and where can and should research be used and undertaken to inform local authority decision-making? Learning from each other to develop research capacity and activity within South Tyneside Council whilst harnessing the benefits of a wider regional research support infrastructure. Background: Health & social care organisations including local government face many challenges. These include an ageing population, more people living with long-term conditions and an increasing demand on services, coupled with ever-increasing scarcity of resources. Austerity and the consequent severe financial constraints, exacerbated by recent events due to COVID 19, mean that local governments are facing deep cuts in public spending (1)) and a situation where public health priorities may suffer (2). Under such circumstances, it is crucial that scarce resources are allocated and decisions are made in such a way to maximise effectiveness, efficiency and equity of services and so provide services that reflect local needs and priorities but ensure health and wellbeing of local populations are maximised. Given the challenges facing decision-makers in local governments, the need to utilise evidenced based approaches to aid local decision-making is crucial. A collaboratively developed research capacity tool kit that is fit for purpose and shaped by multiple stakeholders that can maximise the use and generation of research in South Tyneside Council is the overarching aim of this research proposal. Research Aim: To co-create a research capacity toolkit to enhance the research infrastructure within South Tyneside Council and existing regional research collaborations, to ensure decisions are research informed and made in such a way to maximise effectiveness, efficiency and equity, ensuring optimal maximisation of the health and wellbeing of local populations. Objectives: To conduct a research needs assessment to explore the research needs and capacity of South Tyneside Council in relation to identifying, undertaking, utilising and applying research and evidence to aid decision-making. To explore how South Tyneside Council interacts and collaborates as an active member of existing external research infrastructures both regionally and nationally, creating 'Äúa road map for research'Äù for use by the council. To synthesise findings and co-create in collaboration with the council, a research capacity framework building on existing platforms and gaps in the organisation related to research and its various components. To produce a research capacity development toolkit, incorporating the objectives above. Methods: This will involve multiple methods including scoping of data and documents, focus groups and interviews, evidence mapping and a consensus development workshop. Impact: This piece of work will provide a co-created research capacity toolkit that is relevant to the strategic aims of South Tyneside Council and is readily useable by employees engaged with strategic objectives. Furthermore, it will harness the benefits of further engagement and collaboration with an external research infrastructure provided by a range of organisations across the region who provide extensive expertise, support, skills and strategic direction. This will facilitate the Council'Äôs capacity to further shape not only its own research strategy but that of the wider regional research footprint.",,2021,N/A,59700.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Research on Capacity Strengthening",Other secondary impacts | Institutional level capacity strengthening,2020 +P25449,NIHR132852,Frequent Users of the Emergency Department: Improving and Standardising Services-a mixed methods study,"BACKGROUND: Approximately 2.5% Emergency Department (ED) users account for 10% of total attendances. Many frequent users suffer from mental health and social problems. Services for frequent users have developed recently in a piecemeal fashion and evidence of efficacy of interventions is weak. In previous work we found 80/170 Emergency Departments with frequent user services with 4 different service types. These are: frequent user services based in ED and run by ED staff: frequent user services based in ED and run by mental health staff (liaison mental health teams); frequent user services with in-reach to ED from mental health services; and community based services for frequent users based outside the ED. AIMS: Our aims are to: a) describe current patterns and costs of frequent use of urgent and emergency care (UEC); b) describe the services for frequent users; c) identify predictors of high-cost patterns of attendance, and the impact of frequent user services on attendance; d) identify which interventions appear to work for which types of frequent users and why, and test these findings by in-depth case-studies of 4 different service types; and e) disseminate an implementation framework for frequent user services to improve planning and optimise care. METHODS: Workstream 1: This is a cross-sectional mapping of the current extent of services for frequent users of urgent and emergency care networks in England, and a mixed methods study to characterise 20 representative frequent user services (5 each from 4 different types). From this we will develop early ideas about how interventions may work for different subgroups of frequent users (i.e. safely reduce urgent and emergency care use if appropriate plus/minus provision of additional help and support). Workstream 2: This is a large data study (years 2016/17 to 2020/21) using two complementary datasets. The CUREd dataset links the urgent and emergency care network (ED, 111 and 999) data for Yorkshire and Humber Region. Hospital Episode Statistics data will be linked to ED attendance for the whole of England. The data from CUREd are more finely grained than HES data, whereas HES data provide a national perspective as opposed to a regional perspective capture by CUREd. Together they complement each other. We will: a) identify patterns of frequent use and sub-groups of frequent users; b) examine how frequent users access the whole urgent and emergency care network including attendance at multiple sites; c) study healthcare costs of frequent users to understand where costs are generated and the potential for reduction d) conduct an interrupted time series analysis of the impact on ED frequent users of the introduction of frequent user services. We will also examine the impact of the COVID-19 pandemic on frequent use of the ED. Workstream 3: This involves a realist synthesis to identify and test programme theories about how interventions for subgroups of frequent users produce outcomes. The synthesis will include a realist literature review, and will incorporate the early ideas from workstream 1, 4 in-depth exemplar case studies (one each from the different types of frequent user service) and data emerging from Workstream 2. The synthesis will run iteratively throughout the project to ensure that work across the project is informed by and understood within a testable explanatory framework of cause and effect. Conceptually, it will draw on relevant theoretical models and take a whole systems approach across the urgent and emergency care network at micro, meso and macro levels. Workstream 4: We will develop an implementation framework of 'ideal' models of service delivery tailored for the 4 different types of frequent user service, with a focus on specific interventions for particular subgroups of frequent use. TIMELINE: 0-18months: We will employ staff, set up our programme oversight committee, set-up our PPI reference group, obtain relevant ethics and research governance permissions, begin the analyses using the CUREd dataset, obtain the relevant HES data from NHS digital, start the realist review, conduct the mapping project followed by 20 structured interviews involving frequent user services (5 each from each of the 4 different types). 18-30months: We will carry out 4 in-depth case-site studies, carry out and complete the analyses using the HES data, conduct the main health economic analyses, complete the analyses using the CUREd data, complete the realist synthesis. 31-36months: We will develop the implementation framework with case-site involvement and PPI, disseminate our findings to clinical services via a cascading series of webinars and write up the main results of the programme. DISSEMINATION We will use several different routes to disseminate our findings to relevant stakeholders including top down via NHS England and the medical and nursing Royal Colleges and bottom up via cascading webinars for clinical services plus patient groups. ANTICIPATED IMPACT: We intend to improve outcomes for frequent users of urgent and emergency care networks by optimising services for frequent users, so they provide a safe and appropriate therapeutic response whilst helping to reduce urgent and emergency care use. We will: provide an up-to-date mapping of current services across England and detailed characterisation of four different service types; a characterisation of the different patterns of frequent use of urgent and emergency care and their associated factors; detailed costs related to the pattern and use of urgent and emergency care services by frequent users; an in-depth understanding of why people use urgent and emergency services frequently; a robust evaluation of the impact of frequent user services including likely cost-effectiveness; identification of specific interventions for certain sub-groups of frequent users; understanding of the impact of COVID-19 on frequent use of urgent and emergency care networks; we will develop a framework for frequent user services which will include 'Äòideal models'Äô for each of the different service types; we will distribute the framework to all current frequent user services via a series of cascading webinars; and conduct additional multilevel knowledge transfer at a multinational, national, service and patient/ service user level. Our findings will enable urgent and emergency care networks to make informed planning choices about services for frequent users. We will provide best evidence on how interventions work (or fail) in order to guide on-the-ground delivery. By incorporating PPI in the research we will increase awareness of constructive approaches to this important issue and aim to improve care for people who use emergency care on a frequent basis.",,2025,N/A,1778442.02,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Indirect health impacts | Health service delivery,2022 +P25450,NIHR132914,CICADA-ME: Coronavirus Intersectionalities: Chronic Conditions and Disabilities And Migrants and other Ethnic minorities,"Two groups that experience similar societal inequities (expanded by the COVID-19 pandemic), including in social and health care, are people with chronic conditions/disabilities (PwCD) and ethnic minorities. The worst affected are both ethnic minority AND with chronic conditions/disabilities, a common group, as COVID-19 mortality statistics show. There is a largely unmet expressed need to explore this combined group'Äôs pandemic experiences with new or worsening conditions/disabilities including post-Covid syndrome in relation to reduced services, inequalities, lifestyle changes or health neglect and vaccine uptake. We aim to contribute and inform evidence-based formal and informal strategies, guidelines, recommendations and easily adopted interventions for pandemic-related and future health and social care policy and practice, to mitigate inequities and improve the experiences, health and wellbeing outcomes of minority ethnic groups at the intersection with chronic conditions/disabilities. To do so, we will develop a rich intersectional understanding of their mental and physical health, coping, access to resources, and informal and formal social and health care support experiences, and relevant assets and strengths, longitudinally over 18 months using mixed methods. Our 4 work packages involve a new UK survey in 3 waves, parallel qualitative insights, secondary analyses of other surveys, rapid review, and outputs for immediate use developed with participatory methods, with co-create workshops involving our PPI team and other stakeholders throughout. Our survey (n=5000) samples for 1st and 2nd generation community-dwelling minority ethnic groups and white British comparators, all with/without chronic conditions/disabilities, across the UK'Äôs 4 nations, to determine relationships between measured variables and their trajectories. After Survey Wave 1 we will interview 1st and 2nd generation ethnic minorities from Poland, India and Pakistan, sub-Saharan Africa, and the Middle East, and white British comparisons, all with and without chronic conditions/disabilities, about their pandemic experiences at 5 diverse sites in England, supporting transferability. Interviews (n=210) informed by survey analyses will include social network analysis, photovoice. We will train local lay people to help undertake these remotely; a transformative community migrant-majority research-active group will be our main London co-researcher. This group and a main co-applicant are members of an existing UKRI consortium and have undertaken complementary work at two of our sites, demonstrating the feasibility of our plans. At Waves 2 and 3 research workshops with interviewees will use video vignettes built from earlier study findings. Key informant interviews and co-create workshops will consider implementation. We will synthesise Keyword frequency analysis, Framework, discourse and narrative analyses, Latent Growth Modelling, Structural Equation Modelling, and social network analyses using tabulated evidence to decision methods, with interim findings reported at each wave for early delivery of benefits. Respondent and national UK demographic data will be compared for representativeness, and transferability explored at each stage. Data will be presented separately and combined for ethnic minorities and PwCD. We expect rapid impact from our strong networks and Co-A and collaborator existing strong pathways to influence in health and social policy and clinical practice.",,2022,N/A,1014051.43,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons | Individuals with multimorbidity | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Post acute and long term health consequences | Approaches to public health interventions | Indirect health impacts | Health service delivery,2021 +P25451,NIHR133066,NIHR Global Health Research Group on Gastrointestinal Infections: Facilitating the Introduction and Evaluation of Vaccines for Enteric Diseases in Children in Eastern and Southern sub-Saharan Africa,"Gastrointestinal infections are responsible for over 500,000 deaths annually in children under age five years; the highest mortality rates occur in sub-Saharan Africa. While diarrhoeal deaths have fallen over the past two decades, morbidity remains high. Moreover, improvements in diarrhoeal mortality have not been uniform between and within countries; populations with high rates of malnutrition, poor sanitary conditions and reduced access to healthcare suffer the greatest burden. Enteric vaccines comprise a critical public health tool to reduce the burden of gastrointestinal infections, but applied health research is required to enable equitable population benefit. Work undertaken by the University of Liverpool in partnership with the Malawi College of Medicine and Ministry of Health informed a recommendation by WHO to introduce a vaccine against rotavirus diarrhoea in childhood immunisation programmes across Africa. The roll-out of rotavirus vaccination has reduced diarrhoeal illness and deaths in African children, but in some populations vaccination does not work well, and vaccination is received late or not at all. Vaccines against other enteric infections, including Shigella and Enterotoxigenic E Coli, are urgently needed and multiple candidates are in clinical development. The Global Health Research Group in Gastrointestinal Infections will apply world-leading, multidisciplinary gastrointestinal infection and vaccine research to build capacity and improve health outcomes from childhood diarrhoea in Eastern and Southern Africa. In response to clinical and health needs identified by Ministries of Health and local communities, we will extend our work on rotavirus to include other key, vaccine-preventable enteric infections. We will extend the geographic scope of our work by forging new partnerships in Kenya and Ethiopia, where the burden of diarrhoea is high and research capacity is limited. We will address inequalities in diarrhoea burden by bringing together expertise in social science, mathematical modelling, statistics, epidemiology, health economics and policy with excellent laboratory science to maximise the benefit of enteric vaccines for all children. in Malawi, Kenya and Ethiopia, we will (i) develop sustained engagement with communities and key stakeholders to provide greater national and regional visibility of gastrointestinal infection research; (ii) estimate the clinical and cost burden of vaccine-preventable gastrointestinal infections (rotavirus, Shigella, ETEC) presenting to health facilities, and examine the impact of COVID-19 on disease presentation; (iii) model the clinical impact and cost-effectiveness of vaccination; (iv) create sustainable systems to measure the burden of gastrointestinal infections and the outcomes of vaccine interventions to inform policy decisions; and (v) develop research capacity by training postgraduate (Masters) students and Postdoctoral Fellows in gastrointestinal infection research, leveraging additional support through existing PhD programmes run by the partner organisations. Through close links with Ministries of Health and ongoing community engagement, we will ensure our research is translated into policy for population benefit. Development of a cohort of gastrointestinal infection researchers will sustain this work in the years ahead, helping to reduce the burden of vaccine-preventable diarrhoeal diseases among children in sub-Saharan Africa.",,2025,N/A,3659581.54,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25458,NIHR135108,"Quality, safety and clinical governance in NHS and independent hospitals: lessons from the interface","Every patient has the right to expect safe, high quality care whether they are treated in an NHS hospital or an independent hospital. We propose new research to help understand and improve the quality and safety of patient care in NHS and independent hospitals. Independent hospitals are private sector organisations which provide health care to patients who pay, directly or through private insurance, and which are often also contracted to provide care for some patients funded by the NHS. We will learn about the systems which oversee the quality and safety of patient care, which are often termed 'Äúclinical governance'Äù. Good clinical governance is the foundation of good patient care. The need for this research was demonstrated by the public inquiry into the case of Ian Paterson, a surgeon who worked across both NHS and independent hospitals. He carried out inappropriate and unnecessary operations over many years, finally being suspended from practice, and eventually imprisoned. The inquiry report found he could have been stopped from harming patients eight years earlier and it recommended national changes to improve clinical governance. In 2018 a report from the health regulator also criticised the way independent hospitals monitored and reported on clinical performance, and in response a new framework for clinical governance for independent hospitals was introduced. For the first time, in 2022, information about all patients treated in both NHS and independent hospitals will be brought together in one dataset, and we plan to use this to compare quality and performance and provide information for better clinical governance. The main aim of our research is to understand how quality and safety is monitored across both NHS and independent hospitals and how newly available data can be used to provide information to support this. Our research has four main aims. Firstly, we will describe and compare the care provided in NHS and independent hospitals and how that has changed over time. Secondly, we will observe and assess doctors'Äô work in both NHS and independent hospitals and how clinical governance works. Thirdly, we will examine how the quality and safety of care varies across NHS and independent hospitals (measuring things like readmissions, deaths and patients transferred from independent to NHS hospitals). Fourthly, we will explore how the working arrangements between NHS and independent hospitals have changed during (and after) the COVID-19 pandemic. To do this, we will analyse the new national dataset covering all patients in NHS and independent hospitals. We will also send questionnaires to the staff who lead clinical governance in NHS and independent hospitals, and researchers will visit hospitals to conduct interviews and focus groups with patients who have experience of care in both settings, and to observe and interview doctors and other professionals who work across both NHS and independent hospitals. We have already worked closely with a patient and public involvement group in developing this proposal and incorporated their views into the research plan. We have a PPI co-applicant on our research team, we will have a PPI Forum for the project and will involve PPI collaborators in interviewing patients in our research as well as in the oversight of the project through our project advisory group.",,2025,N/A,1173061.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health service delivery | Health leadership and governance,2023 +P25459,NIHR135315,Improving Social Support and Recovery for Young People Affected by Long Covid: Qualitative Study,"BACKGROUND Understanding how young people learn to live with COVID-19 is critically important. The illness of 'ÄòLong Covid'Äô presents particular challenges. This is because Long Covid can alter young people'Äôs lives at a time when they are making various important 'Äòlife transitions'Äô in relation to education and employment as well as in social and family life. A key issue is how to provide social support to young people affected by Long Covid. In common with other areas of health care, Long Covid services may be inaccessible to many young people, especially those who are most socially disadvantaged. Important questions are how to strengthen the informal care and social support that young people receive within their own social networks, and also how to build patient-led and peer-based responses. By learning directly from young people, qualitative research can help. RATIONALE We have developed the first robust qualitative study of how young people and their social networks adapt to, and recover from, Long Covid. This project is delivered in partnership with Long Covid Kids and Long Covid Support, two leading patient-led organisations. The research leads to practical materials for use in patient-led, peer-based, and social support interventions as well as for use in training and advocacy. APPROACH We interview 80 young people (15-25 years), of whom 40 we also follow-up (6-9 months). Of these, the nominated social networks of 20 young people are interviewed (40-60 network interviews). Our study concentrates on young people who are affected by social and economic inequalities, and we focus primarily on recruiting young people in London, Birmingham and Manchester. We combine interviews with other methods. We take a participatory approach which involves peer researchers. We also undertake consultations with multiple stakeholders to transform our findings into actions locally. We involve young people throughout 'Äì from design to output 'Äì and we collaborate with a creative partner to coproduce interventions materials. We believe this project, and its approach, will help strengthen and better provide social support for young people affected by Long Covid.",,2025,N/A,703887.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25461,NIHR135830,Stratification of Clinically Vulnerable People for COVID-19 Risk Using Antibody Testing (STRAVINSKY),"Background: Although the COVID-19 vaccination program has proved extraordinarily successful, clinically vulnerable (CV) patients remain at risk of SARS-CoV-2 infection, severe COVID-19 and death. Coordinating large (inter)national studies, we have previously identified patients who make sub-optimal immune responses to COVID-19 vaccines, and those at highest risk of severe COVID-19. Although the precise immune correlates of protection against severe COVID19 are not defined, recent emerging data in patient groups suggests that the serological response to vaccination is a critical determinant in COVID-19 outcomes. Disease cohorts may be particularly informative in defining correlates of protection, as vaccine immune responses are heterogeneous such that correlations of these with disease outcomes is possible. The challenge/aims: Previous government advice to CV patients has recommended shielding, and early, repeat COVID-19 vaccination. The provision of ongoing advice is challenging since robust, evidence describing COVID-19 outcomes following additional boosters, the emergence of omicron variants, and the deployment of bivalent vaccines is lacking. Furthermore, QCOVID (a population study of health care records) has identified additional risk factors that enhance COVID-19 risk, with uncertainty as to whether this relates to vaccine responsiveness. We aim to use SARS-CoV-2 antibody testing to quantify COVID-19 risk, enabling clinicians/DHSC to provide on-going targeted advice over the next two years. Methodology: We will conduct a) a retrospective meta-analysis of existing data with the aim of refining CV groups for future follow up; b) a prospective arm of 3000 CV patients. For the retrospective study, we will collate existing data from national studies, including a minimal dataset of key characteristics and vaccine responsiveness. A meta-analysis will refine those disease groups with reduced or heterogeneous antibody levels compared to healthy controls. Groups with antibody levels comparable to age- and sex-matched healthy controls will be excluded from the prospective study. A multicentre prospective, observational cohort study will assess the predictive value of post COVID-19 vaccine serology in CV patients, including disease groups with baseline low/no antibodies (predicted using existing data, QCOVID4, the report from the Independent Advisory Group for COVID-19 medicines and refined following our retrospective analysis). A healthy control group will be provided by the UKRI funded PITCH2 consortium. Serological responses to bivalent vaccines will be correlated with COVID-19 clinical outcomes after infection with omicron lineage and emerging variants. Participants will be remotely sampled (n=2,600) with dried blood spots posted to a central laboratory, facilitating the recruitment of participants with diverse ethnic and socio-economic status. Additional blood and nasal secretions will be collected in 400 participants for immune assessment should serology fail to predict clinical outcomes. Three follow up visits will capture COVID-19 vaccine responses through to 2024. Significant outputs: We will establish if antibody testing can identify CV individuals at greatest risk of severe COVID-19 infection, and if possible, define serological thresholds for COVID-19 risk. We will improve the understanding of COVID-19 risk in CV individuals to inform future clinical care and guidance.",,2025,N/A,3528798.31,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Diagnostics | Immunity | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity,2023 +P25465,NIHR151892,A multi-centre randomised controlled trial examining the effects of temporarily pausing Bruton Tyrosine Kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with Chronic Lymphocytic Leukaemia (including a nested mechanistic sub-study).,"Research question Does a three-week pause of Bruton Tyrosine Kinase inhibitor (BTKi) treatment improve immune responses to SARS-CoV-2 vaccination in people with Chronic Lymphocytic Leukaemia (CLL)? Background CLL is the most common adult leukaemia in the UK and is associated with profound immunosuppression. Patients show increased susceptibility to COVID-19 and display impaired SARS-CoV-2 vaccine responses. BTKi drugs have revolutionised the management of CLL and are also used in other malignancies and some autoimmune diseases. However BTKi therapy inhibits normal B cell responses and our recent UK-wide study of COVID-19 vaccine responses in CLL identified BTKi treatment as the strongest predictor of low antibody response. BTKi therapy is associated with increased bleeding risk and is routinely paused peri-operatively without clinical impact. Pausing BTKi around the time of vaccination could improve COVID-19 vaccine responses leading to better protection against infection and severe disease. Aims To assess if a three-week pause of BTKi treatment improves the immune response to SARS-CoV-2 vaccination in CLL patients whilst maintaining disease control. Method Design A prospective 2-arm parallel group, multicentre randomised controlled trial and nested mechanistic study. Setting: Secondary care. Population Patients aged 18 and over, diagnosed with CLL and taking BTKi therapy for more than 12 months. Randomisation 1:1 individual randomisation stratified by 1st or subsequent line of therapy. Intervention Advice to pause BTKi therapy for 3 weeks (starting 1 week before vaccination) Comparator Continue daily BTKi therapy as usual. Outcomes Primary: 'Ä¢ Anti-spike-RBD-specific antibody titre 3 weeks post vaccination Secondary: 'Ä¢ Anti-spike-RBD-specific antibody titre at 12 weeks post vaccination 'Ä¢ T cell ELISpot response at baseline and 3 weeks post vaccination 'Ä¢ Neutralising titre at 50% and 90% against Wuhan and the current dominant variant 'Ä¢ Disease activity at baseline, week 3 and 12 post vaccination 'Ä¢ Quality of life at baseline and weeks 3 and 12 weeks post vaccination. 'Ä¢ Adherence (self-report) Mechanistic: 'Ä¢ B cell receptor signalling assay assessment of adherence and relationship to antibody generation. Research contact: 1. Pre-vaccine: consent, research assessments, disease activity, blood collection. 2. Randomisation (phone): reconfirm eligibility. 3. Weeks 1, 2 (SMS/phone): adherence to intervention 4. Weeks 3 and 12 post vaccine: research assessment, blood collection. Analysis: Multi-level mixed effects models adjusted for randomisation factors and important prognostic factors using the as randomised population. Sample size: 120 participants (60 in each arm) will allow detection of an absolute difference of 0.65SD effect size (mean difference of 0.97 log10 scale), using 90%, 2-sided a=5% and 15% loss to follow up. 20 participants (10 in each arm) will participate in the mechanistic sub-study and provide additional blood samples for B cell receptor signalling. Timelines for delivery (months) Set up: 1-3 Recruitment: 4-11. Follow up and laboratory analysis: 4-14. Data analysis and write-up 13-18. Anticipated impact and dissemination The results will be disseminated to patients, the public and to our supporting charities. Findings will be published in high impact journals, presented at international conferences and relayed to the JCVI, the BCUK Vaccine Taskforce and BCSH guideline writing group.",,2024,N/A,891991.08,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Clinical trial (unspecified trial phase),2022 +P25468,NIHR153580,SORT: Surgery Or RadioTherapy for early-stage cancer,"Research questions For patients with early-stage non-small cell lung cancer (NSCLC), oesophageal squamous cell carcinoma (OSCC), and muscle-invasive bladder cancer (MIBC), we will ask: a) what impact did the COVID-19 period have on sociodemographic inequalities in receipt of curative versus non-curative interventions? b) what is the relative effectiveness and cost-effectiveness of curative radiotherapy (RT) versus surgery? Background For people with early stage NSCLC, OSCC, or MIBC prognosis is poor. Surgical resection is the mainstay curative treatment for these early stage tumours. Radical RT is a recommended alternative, but there is limited RCT evidence comparing curative RT with surgery. To improve outcomes for these three early-stage cancers it is essential to know which of these curative interventions is more effective and cost-effective. The objectives are: 1. To describe the influence of patient and organisational factors on the use of curative RT, curative surgery or non-curative strategies 2. To assess inequalities in the receipt of curative versus non-curative interventions 3. To assess the effectiveness of curative RT versus curative surgical strategies 4. To assess the cost-effectiveness of curative RT versus curative surgical strategies For each cancer, we will synthesise the findings to report: the curative intervention that is more effective and more cost-effective, inequalities in receipt of curative interventions, and the local organisational and patient factors, that may influence treatment choice. We will report results for time periods before and during the COVID-19 pandemic. Methods The overall design combines linked routine cancer data with insights from clinical panels, and interviews with people with each cancer. We will describe the influence of organisational and patient-level factors on use of curative RT or surgical strategies for each early stage tumour. We will assess inequalities according to sociodemographic characteristics (e.g. deprivation, ethnicity) in receipt of curative versus non-curative interventions for each cancer. We will conduct target trials, that apply the principles of an RCT design to observational data, to assess the relative effectiveness of curative RT versus surgery for each cancer. This will involve drawing on clinical panels to help define the eligibility criteria, and treatment strategy protocols, from the cancer registry data. The main outcome will be two-year mortality from the date of diagnosis. We will assess the comparative effectiveness of curative RT versus surgery adjusting for measured patient and organisational factors between the groups. We will use the patient'Äôs travel time to the nearest RT centre, as an instrumental variable to minimise residual confounding. We will assess the relative cost-effectiveness of curative RT versus surgical strategies for each early-stage cancer. Timelines for delivery: Clinical panels, patient interviews, study protocols (months 0-18); inequalities analysis (months 6-18), target trials (18 to 33), CEA (21 to 33), translation workshop and final project report (33-36). Anticipated impact and dissemination: We will convene a translation workshop with all stakeholders including professional surgical and oncological groups, Public and Patient representatives and policymakers from NHS England and NICE. We will discuss how the overall findings can help improve service provision, patient choice and outcomes for these three major cancers.",,2026,N/A,1132504.25,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25470,NIHR155119,"Neurally adjusted ventilatory assist in the adult critical care unit: A randomized, parallel group, allocation concealed, controlled, open, phase 3 pragmatic clinical and cost effectiveness trial with internal pilot","BACKGROUND Usual ventilator weaning involves the manual adjustment of support settings, which often means treatment is not matched to patient need, resulting in extended duration of ventilation and worse patient outcomes. In contrast, innovative automated ventilation systems such as Neurally Adjusted Ventilatory Assist (NAVA), adapt the ventilator support automatically according to physiological parameters. In NAVA, the activity of the diaphragm muscle is used as a monitor of respiratory drive, and to deliver proportional pressure support in synchrony with a patient'Äôs changing ventilatory need. RESEARCH QUESTION What is the clinical and cost-effectiveness of Neurally Adjusted Ventilatory Assist for patients at risk of extended mechanical ventilation duration? DESIGN A multi-centre randomised, allocation concealed, controlled, open label, phase 3 pragmatic clinical and cost effectiveness trial with an internal pilot SETTING Participants will be recruited in at least 40 adult ICUs across the UK to maximise the generalisability of findings TARGET POPULATION Critically ill adults at risk of extended durations of mechanical ventilation support INCLUSION CRITERIA Adults considered by the ICU clinical team likely to remain intubated and ventilated for >48 hours, with a diagnosis of one or a combination of - Chronic Obstructive Pulmonary Disease - Left and/or right ventricular heart failure - Acute Respiratory Distress Syndrome - Pneumonia including COVID-19 - Acute Kidney Injury EXCLUSION CRITERIA - Imminent death or treatment withdrawal - Contraindication to NAVA feeding tube insertion - Known or suspected portal hypertension - Neurological cause of ventilator dependence (e.g., brain injury / neuromuscular disease) - Domiciliary mechanical ventilation PRIMARY OUTCOME Duration of mechanical ventilation, defined as time from randomisation until first successful unassisted breathing SECONDARY OUTCOMES IN HOSPITAL: Re-intubation; Duration of ICU and hospital stay; Mortality; Adverse events AT 60 DAYS: Health-related quality of life; Mortality AT 6 MONTHS: Health-related quality of life; Mortality; Health service use HEALTH ECONOMIC EVALUATION Cost-effectiveness will be compared at 6 months via a cost-utility analysis from the perspective of the NHS and personal social services SAMPLE SIZE 900 patients TIMELINE Allowing 6 months for approvals and set-up of 10 sites, and a realistic staggered set-up of the remaining 30 sites, the total recruitment duration is 39 months. With follow-up, analysis and reporting, the total grant duration is 53 months EXPERTISE To optimise all aspects of trial delivery, our multiprofessional team includes clinical trialists, physician and nurse national leaders in critical care, clinical experts, physiologists, methodologists, statisticians, health economists, and former patients and family representatives with lived experience of prolonged mechanical ventilation treatment. ANTICIPATED IMPACT AND DISSEMINATION Dissemination will take multiple routes including publication in international high impact factor journals, presentation at relevant national and international conferences, circulation via relevant patient and family networks, and via social media channels. We anticipate significant impact to patients and clinical practice.",,2028,N/A,2572816.61,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management",2024 +P25472,NIHR202107,"Continuous respiration monitoring using a novel, wearable capaciflector sensor for early detection of distress, enabling quicker intervention for improved patient outcomes.","Background to the research Changes in breathing rate are the single earliest sign of patient deterioration in a number of diseases including sepsis and also COVID-19. These almost always precede changes in other vital signs. Every year, thousands of lives are lost due to sepsis and late detection of respiratory disease. The earlier these changes are detected, the more effective the treatment. This can therefore reduce deaths through early targeted intervention and is hence an NHS priority. Chest-band or facemask systems are available for measuring respiration rate continuously but are uncomfortable for use over long periods of time (more than an hour). Aims and methods Respiration rate is the number of breaths per minute. A changing rate is one of the earliest signs of patient deterioration in many diseases. Currently, in hospitals, this is measured by nurses manually counting the number of breaths taken in a minute. It is measured every 4-6 hours, which introduces delays in detecting changes in respiration rate and potential treatment. The aim of this project is to deliver a wearable system that can continuously and accurately display readings and warn clinicians of changes in respiration rate that indicate patient deterioration. The system will also display a profile history of respiration rates to allow longer-term trends to be monitored. The device will be a mass manufacturable, low-cost electronic 'sticker' that wirelessly interfaces to a remote smartphone/tablet. This project will involve clinicians, engineers and public/patients to develop technology (hardware and software), for a new type of respiration sensor, which is comfortable to wear for many days. Data will be displayed on a dedicated smartphone app to the healthcare team, who can use the device as an early warning system and respond promptly. The project will also provide a route to achieve regulatory approval for use within the NHS. The funding will facilitate the formation of a commercial pathway for mass-production of the complete system and allow also intellectual property to be protected. Patient and public involvement (PPI) For a wearable device, it is essential that the public and patients have early input into this project in order to achieve a wearable device with optimal technical performance. PPI will be therefore an ongoing activity throughout the project. In March 2020, we discussed and evaluated early prototypes with six former Southampton Hospital patients, who showed enthusiasm and support for our device and provided excellent feedback regarding its perceived value to patients, wearability, accuracy and cost. We will adopt a variety of dissemination activities including scientific publications and attendance at commercial exhibitions. There will also be a broad engagement to ensure that the general public is aware of the developments and that routes to the NHS marketplace are fully established.",,2024,N/A,1348004.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P25473,NIHR202213,"People living with Diabetes Mellitus and Intermediate Hyperglycaemia: risk of infections, and effects of average level and variability of glycated haemoglobin (HbA1c) on this risk, in people of different ethnic groups","Most people living with diabetes (PLWD) and their doctors worry about developing conditions like heart attacks, strokes, or eye and kidney damage. Improvements in diabetes care by keeping blood sugar levels lower, and using drugs to help prevent heart attacks and strokes (like statins, aspirin, and blood pressure lowering drugs) are reducing these problems. However, PLWD are more likely to get infections, especially bacterial and fungal infections. Some studies suggest that PLWD might be getting more serious infections than previously. COVID-19 has recently focused attention on infection in PLWD and highlighted that people from ethnic minorities are more likely to get severely ill and die. Although there are many explanations for this, for some people this is linked to their diabetes, which is more common in people from some ethnic groups. We will use UK data collected by GPs, data from hospitals and national statistics (death data). Our research team has already worked extensively on diabetes and infections using similar data, however we previously focused mainly on type 2 diabetes. We found that overall, PLWD were about 2-3 times more likely to be treated in hospital for many potentially serious infections, such as skin, bone and joint, respiratory and urinary tract infections, and sepsis (blood poisoning). While we observed potentially higher risks for people with type 1 diabetes, this only included patients aged 40 and over, so we could not provide a comprehensive picture. Our previous work was also unable to consider risks by different ethnic groups, but recent data recording improvements now make this possible. For people with type 2 diabetes, both high longer-term blood sugar levels (HbA1c) and changes in HbA1c levels over time were found to increase the chances of getting serious infections. We are now planning to examine the links between living with diabetes, high HbA1c, and changes over time in HbA1c, and infection risk for all PLWD and in different ethnic groups. Diabetes UK have identified this as a priority research area. We have started involving PLWD and we will develop this involvement further including a patient advisory group to inform the project throughout its timeline and help with dissemination. Our work has important clinical implications; we previously showed that less stable levels of blood sugars may be more important than higher sugar levels in increasing risks of infections and other complications and premature death in people with type 2 diabetes, yet targets for control focus most on HbA1c levels, not on reducing instability. Our work could also help development of future interventions specifically to reduce infections in PLWD. Finally, better knowledge of infection risks and their links with diabetes and ethnicity would inform the response to any future waves of COVID-19 and similar pandemics.",,2024,N/A,207303.3,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management",2022 +P25475,NIHR202500,Provision of multidisciplinary COVID-19 technical advice & recommendations to improve the COVID-19 outbreak response in Istanbul'Äôs urban slums,"On invitation of Dr Tuna Kuyuzu & Dr Deniz Mardin and in response to Istanbul s ongoing difficulty in controlling it s COVID-19 case burden, travel to Istanbul between 31st October-29th November 2020; Undertake field trip & situational analysis of Istanbul s slums to examine; (a) slum-dweller COVID-19 awareness, perceptions, resilience and risk factors and (b) success/failures of COVID-19 outbreak response to date Provide recommendations & technical expertise to both above whom are closely involved with Istanbul s Ministry of Environment & Urban Planning that is coordinating the city wide COVID-19 outbreak response & several NGOs (Mekanda Adalet Dernegi, 1 Umut & Tarlabasi Solidarity Association) whom are specifically working in these high risk populations Based in Bogazici University with desk space provided but regularly undertaking field trips to slums in Tarlabasi (Istanbul) in collaboration with above named NGOs",,2021,N/A,11535.18,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease susceptibility | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Policy research and interventions,2020 +P25476,NIHR202660,Recovery from COVID-19 within the Children and Young Peoples Secure Estate (CYPSE): A mixed-methods study of wellbeing,"Background: Living with Coronavirus has been hard for everyone. Children in prison have faced a lot of limits on what they can do. They may have been locked in their bedrooms, not been able to see or talk to their families and not been able to go to school. Children in prison have lots of mental health problems, more than those in the community. They often hurt themselves, other children, or staff working in the prison. Coronavirus and how the prisons have had to deal with it, might have changed how often children hurt themselves or others. Aim: We would like to see what Coronavirus has done to how children in prison feel and how often they have hurt themselves or others. We want to do this to help make the prisons better and safer places for children. Design and methods: This project is split into three parts and they all link together. In part 1 we will get numbers that are already collected about how often young people hurt themselves and hurt others in the different prisons. We will look at these numbers before and during Coronavirus to see if there are changes. In part 2 we want to talk to staff who work at each prison to find out how the prison dealt with the virus and what changes they made to how the children were looked after. We want to do this to help see if any of the changes increased or decreased the harms in part 1. In part 2 we also want to talk to some children, their families, and staff in more detail about their experiences during Coronavirus. In part 3, we will put the information from part 1 and 2 together. We will then show this to children in prison, their families, staff who work in the prisons and the people in charge of the prisons to help us make a list of changes. These changes might be about making the prison safer, or a better place for children, or what the prisons might do differently during Coronavirus or if we have a new virus in the future. Patient and public involvement: Children at a prison called Wetherby have helped write this Plain English Summary. They have made us think about what questions we should ask. They will help us write information about the project, work with us to make the list of changes and with telling other people what we find. The children in Barton Moss, another prison, will help too. Dissemination: At the end we will share what we find with the help of the children and staff. This will be by writing reports and telling people at meetings.",,2022,N/A,221870.88,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts | Social impacts,2021 +P25478,NIHR203051,A feasibility trial of remotely-delivered Video Interaction Guidance [VIG] for families of children with a learning disability referred to specialist mental health services,"Challenging behaviours and mental health problems are 3-4 times higher in children with a learning disability (LD) compared to typically developing children. They can lead to family breakdown and out of family placements. The National Institute for Health and Care Excellence (NICE) recommends that services support families to manage effectively at home. Children with LD and behaviour or mental health problems are referred to specialist child mental health services for support. These services are increasingly under strain, particularly during the COVID-19 pandemic. Remote therapy could increase the reach of therapies that can help these families. Video Interaction Guidance (VIG) is increasingly used in specialist mental health services to help families. VIG is a brief, personalised, strengths-based intervention: it uses video to identify successful moments of communication between a parent and a child as a tool to improve parent-child interaction and relationships. The quality of the parent-child relationship affects the risk for challenging behaviours and mental health problems in children with LD. VIG has been offered remotely since the start of the pandemic. However, to date, there has been no robust test of VIG or remote VIG. Parents may not want remote therapy or a therapy that focuses on the parent-child relationship. We also do not know what the main effects of VIG are for these families, and whether any gains made from the therapy are present six months later, a time when parenting intervention effects are expected to be present. To determine if VIG works well as a remote therapy, the first step is to determine if we can recruit parents to a study and if they like VIG. Working alongside parent advisors and the Challenging Behaviour Foundation, we will recruit 50 parents with a 6-12 year-old child with LD referred to specialist child mental health services. Parents will be allocated by chance (randomly) to receive VIG remotely alongside the usual service support or just the usual service support. We will follow families up to 6 months to measure: how many parents are recruited to the study; how many stay in the study at 6 months and complete the study questionnaires; how many families complete VIG, whether remote VIG is acceptable to families and services, and what factors make it easy or difficult to offer or take up remote VIG. At the end of the study, we will determine, using pre-specified criteria, if we can proceed with testing in a large multicentre trial whether VIG is an effective therapy delivered remotely within specialist mental health services. We will communicate findings to parents, specialist mental health services and researchers.",,2024,N/A,298248,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health financing,2022 +P25480,NIHR203243,"A single-blind, phase IV UK multi-centre randomised controlled trial to determine reactogenicity and immunogenicity of COVID-19 vaccines administered concomitantly with seasonal influenza vaccines","Mass vaccination against COVID-19 started in the UK in early December 2020 and is likely to continue until mid-2021. Whilst rates of COVID-19 infection have decreased, the emergence of variants of interest and planned easing of lockdown measures has led to predictions of potential resurgence of infection from autumn 2021. The duration of protection of the current COVID-19 vaccines is unknown but it may be that further booster doses will be required in 9 to 12 months time with current or potentially strain-modified vaccines to afford continued protection into the autumn. The timing of the booster doses is likely to coincide with seasonal influenza vaccination, which is usually September to February. Delivering COVID-19 and influenza vaccines at separate appointments will cause significant logistical challenges therefore it would be desirable to immunise with both vaccines at the same appointment, in different arms. The ComFluCOV trial will determine the safety, as well as the immune responses, to administration of the currently approved COVID-19 vaccines at the same time as the recommended influenza vaccines from the 2020/21 season. Participants who are having their second COVID-19 vaccine will be randomised into two groups; one group will receive the influenza vaccine and the other group will receive saline (placebo) at the same time as the COVID-19 vaccine. Participants will not know whether they receive the influenza vaccine or the placebo. After 3 weeks participants who received the influenza vaccine will receive the saline injection and participants who received the saline injection will receive the influenza vaccine. Participants will be followed up for a further 3 weeks after the second injection. We hope to recruit 504 participants into the trial. The trial will be conducted in at least 5 UK NHS centres. The trial is expected to take about 6 months to complete.",,2025,N/A,4168302.42,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Phase 3 clinical trial | Vaccine trial design and infrastructure | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P25482,NIHR203871,"A single-blind, randomised, phase II multi-centre study to determine reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules in adolescents (COMCOV-3)","The successful roll-out of COVID vaccines such as COVID-19 mRNA Vaccine BNT162b2 and the Oxford/AstraZeneca ChAdOx1 nCOV-19 vaccine has saved approximately 60 000 lives in the UK alone up to July 2021. Both of these vaccines are administered as a two-dose regimen, as is the adjuvanted protein COVID-19 vaccine from Novavax, NVXCoV2373, which is under rolling review of the MHRA at the time of writing. The use of heterologous prime/boost (mix and match) schedules of COVID-19 vaccines has already been studied in COMCOV and COMCOV2, and a schedule with ChAdOx1 nCOV-19 as the first dose, followed by BNT162b2 as the second dose has been shown to be highly immunogenic and is now deployed routinely in non-elderly populations in Canada and many northern European countries. Use of heterologous prime/boost schedules could also potentially be of benefit in an adolescent immunisation campaign. The potential benefits (and costs) of extending the UK COVID-19 vaccine immunisation to adolescents in the UK is under active review by the JCVI, and on 4th August 2021 it was announced that a first dose of BNT162b2 was recommended for all 16 to 17-year olds in the UK, with decisions about the timing and nature of the second dose to be decided. One concern regarding adolescent immunisation is a rare side effect of inflammation of the heart muscle (myocarditis) or lining of the heart (pericarditis) that has been observed after the second dose of BNT162b2, especially in young men. Mixed schedules with alternative vaccines used for the second dose, or using half doses of COVID-19 vaccines, could be an alternative that allows protection against COVID-19 while avoiding a second full dose of BNT162b2, and could also help deploy existing stocks of vaccine as effectively as possible. Accordingly, this study will determine the side effect profile, and the immune responses, following schedules using BNT162b2 as a first dose, and a second dose administered 8 weeks later of either BNT162b2 (full or half dose) or NVXCoV2373 (full dose) or an alternative mRNA produced by Moderna (half dose).",,2024,N/A,7378333.2,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Phase 2 clinical trial | Characterisation of vaccine-induced immunity,2021 +P25485,NIHR204404,Coronavirus and people with learning disabilities study: UK Survey Wave 5,"The proposed 9-month project builds on a completed project that tracked the experiences of approximately 800 adults with learning disabilities through the COVID-19 pandemic. This UK-wide project interviewed about 500 adults with learning disabilities directly (by Zoom, Teams, phone, or other ways of being in contact remotely) and surveyed a further 300 family members or support workers of adults with learning disabilities who could not take part in an interview. The project heard from people at three time points: in the winter of 2020/21 (mainly during lockdown), in the spring of 2021 (when some public health protection measures had been eased), and in late summer 2021 (when most protection measures had been lifted). The questions asked in the project were guided by policymakers, people with learning disabilities and family members, with some changes in the questions over time depending on changing circumstances. We asked questions about: health, mental health, and wellbeing; new/worsening health problems; contact with health and social care services and professionals; COVID-19 infections, vaccinations and testing; paid jobs and volunteer work; getting online; contact with friends and family; bereavement. In the online surveys, we also asked family carers and support workers a small number of questions about their own health and wellbeing as carers. The proposed project will go back to the people, family carers and support workers across the UK who took part in the original project, almost all of whom said they would be happy to be contacted about taking part in a future wave. We will use interviews and online surveys again, using the same approaches that people will be familiar with, to find out how people and families are managing as the UK recovers from the COVID-19 pandemic. We will keep some of the central questions the same (for example, health and wellbeing; access to health and social care services) to find out people's experiences over time. As before we will proactively gain the views of policymakers, people with learning disabilities and family members in deciding which questions to keep, which questions to drop, and which new questions to add. We plan to go back to people in late summer/early autumn 2022. In addition to this, we propose two specific new pieces of work in England only: 1) to recruit an additional booster sample of adults with learning disabilities from minority ethnic communities (100 interviews and 50 surveys); 2) to carry out in-depth qualitative case study research concerning up to 20 people with learning disabilities about their journeys through the pandemic. As with the previous project, the proposed project will produce findings from the project quickly, and (in collaboration with partner organisations) in multiple formats to facilitate wide sharing and take-up of the findings.",,2023,N/A,512743.81,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25487,NIHR204677,National Immunisation Schedule Evaluation Consortium (NISEC) II,"In 2018, the National Immunisation Schedule Evaluation Consortium (NISEC) was created to explore vaccines in the UK. It was composed of scientists and doctors from six UK universities and Public Health England. With funding from the UK government, NISEC looked into new vaccines and immunisation schedules, including those for whooping cough and meningitis. NISEC also received additional funding from vaccine manufacturers to run clinical trials relevant to national UK vaccine policy, providing value for money. From early in 2020, the NISEC team focused their efforts on urgent COVID-19 vaccine trials. These trials enrolled about 13,000 participants at 30 UK trial sites, providing important evidence for national and international health policy makers. NISEC expertise was also used to help develop the Oxford-AstraZeneca COVID-19 vaccine, which is thought to have saved 6.3 million lives worldwide in 2021. NISEC is now seeking £6 million from the National Institute of Health Research (NIHR) to continue its work. The new network will include researchers from across the UK and will focus on projects that inform UK vaccine policy, as determined by expert advisors. These projects may include investigating new vaccines against diseases such as pneumonia and shingles, and developing template study designs that can be quickly used for vaccine trials in future pandemics. NISEC will listen to advisors who represent patients and the public, including people from different ethnic backgrounds. The team will share their findings with the experts who make decisions about vaccines in the UK (the Joint Committee on Vaccination and Immunisation or JCVI) to help them decide how to use vaccines in the best way possible. This will lead to preventing infections, reducing suffering and saving lives.",,2026,N/A,7693660.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2023 +P25488,NIHR204688,Development of sub-20 minute PCR-based diagnostic assays for a current point of care testing device,Not Available,,2023,N/A,27242.58,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P25489,NIHR204942,Adaptation and validation of a patient-reported outcome measure capturing Long COVID symptom burden in adolescents: The Symptom Burden Questionnaire for Long COVID in Young People (SBQ-LC-YP),"What s the problem? Long-term symptoms of COVID-19 infection are called 'Long COVID'. Up to 14% of children and young people who catch COVID-19 have Long COVID symptoms 3-months later. People with Long COVID report over 200 different symptoms. Long COVID questionnaires are available for adults, but these do not measure impacts unique to young people such as effects on schoolwork or development. There are no Long COVID symptom questionnaires for young people. What s the solution? The Symptom Burden Questionnaire™ for Long COVID measures Long COVID symptoms in adults. It was designed with patient input according to international guidance. We aim to adapt this questionnaire to make it suitable for young people (11-17 years). Adapting this questionnaire will help understand Long COVID in young people and be used to see if treatments work. How will we do this? First, we will adapt the questionnaire to make sure it includes symptoms important to young people. Second, we will test the questionnaire to understand how well it measures Long COVID symptoms. Part 1: 15-20 healthcare professionals, researchers, parents, and adults with Long COVID will review the questionnaire to check if it is suitable for young people. We will remove unsuitable questions and add new questions if needed. We will interview 28 young people with Long COVID (aged 11-17 years) and their parents/carers (n = 28). A young person can choose to be interviewed with their parent/carer or on their own. Each young person will complete the questionnaire. They will tell us what it was like to answer the questions and if the questions ask about symptoms important to them. We will ask if anything important is missing. We will ask parents/carers for their views. We will use this information to adapt the questionnaire. Part 2: 500 young people with Long COVID and 250 parents/carers will answer the adapted questionnaire using their mobile phone, computer, or paper form. We will use their answers to improve the questionnaire's design and to describe how well it measures Long COVID symptoms in young people. We will do this using statistical tests. Patient and public involvement and engagement People with Long COVID helped to design this research. Young people with Long COVID and parents/carers will work with us on each part of the study. How will we share the results? We will present the results at conferences and publish them in a scientific journal. We will share them with young people, parents/carers, schools, health professionals, and the public. The questionnaire will be available for researchers and healthcare professionals to use. They can use the questionnaire in research studies and in clinics to measure the impact of Long COVID and to find out if treatments for Long COVID work.",,2024,N/A,188791.47,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25495,NIHR206003,"Planning and initiating regulatory approval for a new RF coil designed for polarised xenon MRI of the human lungs, this being introduced to give improved diagnosis and treatment planning of respiratory disease.","Respiratory diseases create a massive UK healthcare burden with 1 in 7 people having lung disease, costing the NHS > £6 billion PA, they are the UK s 4th-highest killer and are the most neglected disease in terms of advanced diagnostics and effective treatments. Clinical diagnostics largely rely on blunt respiratory function breathing tests and CT imaging of lung structural change (with its radiation burden). COVID-19 has highlighted their inadequacy and exacerbated a desperate need for safe means of monitoring the lungs in the longer-term. The lungs currently cannot be adequately imaged by commercially available 1H MRI systems provided by any of the main MRI vendors. The technology and applications of inhaled hyperpolarized xenon-gases to allow highly sensitive MRI of the lungs has been shown at a research level to demonstrate very effective diagnosis and treatment planning in a wide range of respirator diseases. It is now being transition to the clinical applications and all new technologies need to pass the request regulations for each territory. In order to produce polarised xenon MR images, existing scanners require two additions A xenon polariser. This is being developed and commercialised by the University of Sheffield but is not part of this grant application An RF coil optimised to detect xenon MR signal from the lungs. This is being developed by PulseTeq in collaboration with the University of Sheffield. The concept design has been completed successfully and has been followed with an operational prototype. This has demonstrated first class results and on this basis, the company has decided to complete the remaining steps required to launch the device as a commercial product. This grant addresses the question: what steps are required for the new RF coil developed by PulseTeq for xenon MR imaging to meet all the necessary regulations and how to ensure that they are implemented successfully, economically and efficiently. The grant will review the regulation, create a detailed plan and prepare the first device necessary for initial regulatory tests and for assessment in a patient and public initiate study at the University of Sheffield.",,2023,N/A,52848.51,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25496,NIHR206016,Pre-clinical evaluation of 'cleaner burs' - for safer dental aerosol generating procedures,"Many procedures that a dentist performs, including tooth fillings, require the use of a dental drill. Attached to the drill is a bur which is the short cutting tool that has been designed specifically to cut tooth surfaces. Dental burs insert into the dental drill and rotate at high speeds with water being used as a coolant to prevent overheating. At the beginning of the COVID-19 pandemic it was recognised that saliva containing large quantities of coronavirus could mix with the coolant water and encounter the fast-spinning dental bur. As a result, a fast-moving aerosol made up of billions of small droplets could be ejected from the patient s mouth into the room environment. Many of these droplets are contaminated with saliva, and possibly virus, and because of their small size they can remain suspended in the air for long period of time. Because of this there have been many changes in the way that dentistry is now provided including the dental staff having to wear enhanced personal protective equipment and a reduction in the number of patients that can be seen per day. In this project we will test new types of dental bur that have been designed to irreversibly mechanically damage any bacteria or viral particles that are emitted in aerosol droplets so that they are no longer a risk. Ultimately the aim is to make dental surgeries a cleaner environment for both the patients and the staff. So far, we have demonstrated that the burs have a significant effect in laboratory tests but we must now prove that they also work when a dentist is using the burs in the same way they would in real life. To do this we will conduct simulations using mannequins with an artificial mouth and with dentists carrying out a series of common drilling procedures. To test the effect of the new burs, we will use a virus harmless to humans, known as a bacteriophage. We will put bacteriophage into artificial saliva in the mannequin and measure how far it is spread in the dental surgery and how much of the virus then remains intact and capable of transmission. We have chosen a specific bacteriophage because it resembles the size and structure of the novel coronavirus, but the work is relevant to a wide range of microorganisms that are concentrated in the fluids of the mouth. If these tests are successful, we will be ready to begin trials in dental clinics with patients. During the course of this study we intend to discuss the technology with patient representatives in order to help us understand how best to design future clinical studies and identify any concerns there may be about the technological approach.",,2023,N/A,62431.25,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Dentists and dental staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,Innovation,,,,,Infection prevention and control,IPC in health care settings,2023 +P25497,NIHR302206,How can our communities in Bolton come together to make sustained change and accelerate our progress towards net-zero carbon emissions?,"The aim of this research is to understand how we can enable individuals, businesses and communities to come together to make sustained change and accelerate our progress towards Bolton's net-zero carbon emissions. There is currently a climate change emergency as global temperatures rise every decade, causing more profound environmental and health impacts, from rising sea levels and melting ice caps to air quality, food insecurity and increased frequency of extreme weather events such as flooding. There is a need therefore to reach net zero carbon emissions sooner to limit the impact of climate change. In Bolton, our target around reducing carbon is net-zero by 2030, which means that all the carbon released into the atmosphere is balanced by the amount of carbon captured in the atmosphere resulting in net-zero. Recent learning from Bolton's response to COVID and the Variants of Concern, through surge testing and surge vaccinations, highlighted the importance of the community as a key delivery partner in that emergency response which resulted in the halting of rising COVID cases. The community were a key partner from the start helping to shape the response raising awareness through word of mouth, social media and leafleting and also delivering the response. They provided assurance and delivered messages via the 'trusted voice', they developed their solutions responding to the need of the community. Many of these interventions grew organically and the community started to identify new ways of engaging and delivering to the community. This study will build on the community response to Bolton's Variant of Concern, taking lessons learnt and distilling that to enable a similar social movement for the climate change agenda so that we can accelerate change towards our net zero carbon emissions target. The design and methods used will be participatory community engagement whereby the research is co-designed in collaboration with the community and the community will be involved in every stage from designing, delivering, collection and sharing of the results. The methods used will ensure that all voices are heard, not just the strongest voices, contributing to reducing health inequalities. Local authorities across the UK have climate change as a high priority so the findings will be captured in written reports and shared across networks and at conferences where appropriate.",,2025,N/A,372687.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Other secondary impacts,2022 +P25500,NIHR302634,"PARROT: Penicillin Allergy, Antibiotic Resistance and Patient health OuTcomes","JARGON BUSTER: Antibiotic: A medicine used to treat infections caused by bacteria. Antibiotics work by killing bacteria. Antibiotic resistant bacteria: 'Superbugs like MRSA'. Bacteria that have changed so they are no longer killed by antibiotics. Antimicrobial resistance/AMR: A term used to describe the development of antibiotic resistant bacteria. Bloodstream Infection/BSI: A serious infection caused by bacteria in the blood. PARROT: Fellowship study's short name. Penicillins: A common group of antibiotics. Penicillin allergy/PenA: When your immune system reacts abnormally to penicillin, wrongly thinking it is harmful. BACKGROUND: Antibiotic resistant bacteria have a huge impact on patients and the NHS because infections involving these resistant bacteria mean our usual antibiotic treatments will not work as well. People who are affected take longer to get better from common infections and are more likely to die from serious infections e.g.bloodstream infections (BSI). This problem is often called AMR. AMR is caused by overuse and misuse of antibiotics. Penicillins are the first-choice treatment for many common infections. People who have Penicillin allergy/PenA are treated with different, non-penicillin antibiotics. People with PenA are typically prescribed more antibiotics overall, partly because the alternative antibiotics fail to clear the infection. Research has shown that although many people have PenA labels in their notes, most of these people (9 in 10) do not actually have a true allergy when they are tested by a specialist, which means antibiotics are being misused and overused. HEALTH NEED: PenA labels have been linked with 'superbugs', however the full impact of PenA on AMR is unknown. In particular the impact of PenA on AMR and health outcomes in patients treated for BSI and COVID-19 (both of which can cause life-threatening sepsis) is not known. We know that antibiotic use can affect the bacteria that normally live in our guts and mouths. These help us digest food and prevent infections. The more antibiotics are used, the more likely it is that these helpful bacteria are 'killed off', leading to harmful bacteria growing in their place. These harmful bacteria may be able to cause infections, or have genes that make them resistant to antibiotics, or both. See https://youtu.be/r_50QNX0-t0 AIM: To understand the links between PenA, AMR and patient health outcomes in order to improve antibiotic use. METHODS: PARROT is organised into three workstreams: Firstly, I will use a large collection of patient data provided by the PIONEER Health Data Research hub, who hold anonymised data on patients admitted hospital. This data will be used to see if PenA patients who have BSI are more likely to have AMR. Secondly, using data from the NIHR funded PEACH study which is investigating antibiotic use in patients with COVID-19, I will carry out a study to find out the effect of PenA on AMR and patient health outcomes in patients admitted with COVID-19. Thirdly, I will work with the ALABAMA trial, a NIHR-funded trial which aims to remove incorrect PenA labels through pencilling allergy testing. I will recruit ALABAMA trial participants, to carry out a study within a trial that will explore if removing incorrect PenA labels results in reduced AMR. PATIENT AND PUBLIC INVOLVEMENT (PPI): Jenny Boards (PPI lead contributor) has brought her 'PenA lived experience' to co-design PARROT, guiding simplification of the scientific language, and ensuring a patient benefit focus. DISSEMINATION: This research will benefit patients, healthcare workers and policymakers by providing the evidence to support better antibiotic prescribing and help limit AMR. It will tell us if removing incorrect PenA labels results in less AMR. Results will be shared through presentations at scientific meetings, publications in journals and a short video co-developed with PPI-contributors.",,2027,N/A,403076.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25503,QCovid 4,"Predicting risk of death and hospitalisation from COVID-19 in adults during the Omicron Wave in England, between 11 December 2021 and 31 March 2023",Data team/Uber use to query portfolio.,,2023,N/A,286693.75,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Department of Health and Social Care / National Institute for Health and Care Research (DHSC-NIHR),United Kingdom,Europe,,,,,,,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2022 +P25506,474531,Impact of COVID-19 public health measures and lockdown on maternal and neonatal health,"The COVID-19 pandemic has brought exceptional challenges to global health. In Canada, a lockdown strategy was announced in March 2020 as a plan to control the spread of the novel coronavirus. However, there is an increasing concern that the pandemic lockdown might have negatively affected health services and patient outcomes, including mother and infant health. In many instances, the decreased access to health services created sub-optimal mother and infant care. In fact, primary studies show that pregnancy adverse outcomes, such as stillbirth, may have increased during the pandemic, merely due to the lockdown effects. Despite the increasing evidence of the negative effects of COVID-19 infection on pregnant women, studies evaluating the effects of the pandemic restrictions on pregnant women and newborns have shown conflicting results. My project has several goals that target this knowledge gap. First, we aim to compare the pregnancy outcomes occurring before and during the pandemic, focusing on the major pregnancy and newborn outcomes. Second, we will examine major medication classes used among pregnant women pre- and during the COVID-19 period. Third, we will examine the adequacy of health care received by pregnant women during this stressful period. We will use real-world data of linked mother-infant records from over 70,000 pregnancies to highlight the impact of pandemic restrictions on mothers and infants in Manitoba. Our studies can provide evidence to improve mother and infant's health care and prevent negative outcomes during future waves and pandemics.",,-99,University of Manitoba,110119.22,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P25507,465801,Discourse on COVID-19 and illicit drug toxicity on social media,"The illicit drug overdose crisis in North America has had a profound impact on individuals, families and communities, often leading to premature loss of life and lowering of life expectancy. Since 2016, British Columbia (BC) has been experiencing an epidemic of toxic drug supply leading to a large increase in the number of drug overdose events and related deaths. Coronavirus disease 2019 (COVID-19) and measures taken to limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, have directly and indirectly disrupted access to healthcare and social services worldwide, including harm reduction and social support services. Since the beginning of the COVID-19 pandemic, BC witnessed large increases in drug overdose related deaths, with 2021 being the deadliest year. This requires scaling up of existing interventions and introducing new, targeted interventions to address the overdose crisis. The level and type of response is also affected by the perception of the population towards health issues and debate on intervention options. The information available on social media could help decision makers understand the public discourse about opioid use and intervention options. In this project, the overall aim is to understand public perceptions and discourse related to overdose in social media using Artificial Intelligence (AI) methods and techniques to inform the overdose response.",,-99,B.C. Centre for Disease Control (Vancouver),84603.63,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2022 +P25508,486510,Importance of rurality on the impact of a frontline telemedicine tool for the elderly,"During the COVID-19 pandemic, telemedicine has become a lifeline to maintain access to healthcare professionals, especially for older adults who have been particularly impacted by physical distancing measures. In particular, going forward, telemedicine offers new opportunities to improve access to care for older adults living in rural areas, who are disproportionately affected by access barriers such as distance, transportation, and mobility. Despite the potential of telemedicine, few studies have examined the extent to which rurality can influence the impact of telemedicine tools for older adults. My research project therefore aims to 1) measure whether living in a rural area can affect the effectiveness of a telemedicine tool for older adults; and 2) understand and contrast the experiences of older adults living in rural and urban areas who use this telemedicine tool. I will use a telemedicine tool made in Quebec, ESOGER, which allows for rapid assessment by telephone of the physical, mental and social needs of elderly patients. Since the beginning of the pandemic, ESOGER has been used to assess the needs of more than 10,000 elderly people in various community settings at the recommendation of the Ministry of Health and Social Services. The project is original in its use of high-quality research methods to understand the best conditions for applying telemedicine especially to the elderly. Ultimately, the project will help to better organize care for the elderly and thus help improve their quality of life.",,-99,Université de Montréal,13021.09,Human Populations,Unspecified,Older adults (65 and older),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery,2022 +P25510,448879,Impact of Frailty and Sarcopenia on Post-COVID Recovery,"Older adults infected with COVID-19 have a death rate that is 20-40 times higher than young adults, and if they survive their recovery is often protracted and marred by functional decline and disability. Age cutoffs have been proposed for resource allocation though discriminating based on chronological age presents ethical issues and disregards the heterogeneity in health status that could range from vigorous to severely dependent in patients of similar age. Frailty captures this heterogeneity to better support treatment and disposition decisions, and inform post-hospital care needs. We and others have demonstrated that frail patients are 2 to 3 times more likely to suffer deaths, complications, and sequelae of functional decline and poor health-related quality-of-life. These sequelae are pervasive after resolution of the COVID-19 infection and have become known as the post-COVID-19 syndrome. While advanced age has been identified as a risk factor for PCS, this syndrome remains unpredictable and there has surprisingly yet to be a study examining the effects of frailty and sarcopenia (low skeletal muscle mass). A reason for this knowledge gap is the lack of consensus on how to measure frailty in COVID-19 patients since many frailty questionnaires and physical tests are not feasible because of patient acuity, personnel availability, and confinement precautions. One opportunistic approach to gain insights into multiple facets of frailty without extra time or cost (and without extra exposure to COVID-19) is to leverage routinely collected data including imaging and blood tests. While such tests are requested for clinical indications unrelated to frailty, they leave behind a wealth of untapped information about the patient's frailty, body composition, physiological status, and clinical risk.",,-99,CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General,373531.27,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25512,459206,Vaccine Distribution Approaches for Equity-Deserving and At-Risk Populations during COVID-19: Best Practices and Lessons Learned in Canada,"The World Health Organization has stated that one of the worst threats to overcoming COVID-19 is vaccine hesitancy. Vaccine hesitancy amongst underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution since it can result in poorer health outcomes, increased COVID incidence and less vaccination in underserved communities. Approaches for the effective distribution of vaccines for equity-seeking and at-risk individuals are urgently needed. This pan-Canadian study of British Columbia, Alberta, Manitoba, Ontario, Quebec, Nova Scotia, and Newfoundland will identify effective vaccine distribution approaches and advance knowledge on how to design and implement these approaches to meet the needs of communities and reduce the risk of health and social inequalities during and after COVID-19. An exploratory, multi-methods, case study design will be used to conduct a cross-case analysis of seven provinces in Canada. Each case will comprise of: (1) qualitative interviews with policymakers and public health officials; (2) quantitative data analysis of populations served by vaccine distribution approaches; and (3) focus groups with regional stakeholders, providers, patients, and caregivers within effective vaccine distribution models. A thematic analysis of interviews and quantitative data analysis will help identify effective approaches. Focus groups with equity-deserving individuals, caregivers, healthcare providers and other key informants will identify the factors (provincial/federal, structural, community, family, personal) that were enablers or barriers to implementing vaccine distribution programs. A cross-case-study analysis will be done to identify similarities and differences. The outcome of this study will be recommendations for the implementation of equitable and effective vaccine distribution approach(es) in Canada.",,-99,University of Toronto,389339.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Research to inform ethical issues | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Research to inform ethical issues in the Allocation of Resources | Policy research and interventions,2021 +P25514,448915,Covid-19 effects on ARTErial StIffness and vascular AgiNg (CARTESIAN) study- Canada,"During acute infection, COVID-19 affects the respiratory system. However, COVID-19 could damage blood vessels directly and indirectly, pushing people towards a process called premature vascular aging. This process may occur long after the recovery from the infection. Premature vascular aging is worrisome as it usually leads to increased risk of heart, brain and kidney diseases. As part of an international study, we aim to examine if and to what extent, COVID-19 affects blood vessels, and to identify the potential mechanisms involved. We request the support of the CIHR for the participation of the Canadian population in this international fight against the long-term health consequences of COVID-19. While examining the impact of COVID-19 on vascular aging, through our interdisciplinary team of investigators, we will also examine the contribution of various possible mechanisms through which COVID-19 could impact vascular aging. Therefore, we will also study kidney function, clot formation, and anomalies in sugar and fat metabolism that may affect vascular aging. Our research is important and there is an urgency for supporting this study as COVID-19 survivors could be at a higher risk of cardiometabolic complications. The CARTESIAN study is designed to identify and quantify such risk, giving us the opportunity to propose timely preventive measures to reduce the chronic burden of COVID-19, which will be important even once the pandemic is under control.",,-99,Université Laval,275878.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2021 +P25516,462706,Community-partnered infectious disease modeling to inform Covid-19 policies and advocacy in Nunavik,"In mid-October 2021, Covid-19 finally arrived in epidemic form in Nunavik. At the time of writing (November 21, 2021), 817 Nunavimmiut have been diagnosed with Covid-19. The incidence in the region is currently 5836 per 100,000 over a 45-day period. Life in the region has been heavily impacted, including closure of schools, non-essential businesses, and limitations on intra- and extra-regional travel. Public health and medical services policymakers have to make decisions, quickly, in such circumstances. Nunavik is distinct with respect to demographics, geography, availability of medical services, socioeconomic conditions, and its historical-political context. This uniqueness means that copy-pasting tools and choices that have been used in southern Quebec will not suffice. One tool that has been used around the world to help guide public health and medical policy decisions in the face of Covid-19, is infectious disease modelling. At the onset of the fall 2021 covid-19 outbreak in Nunavik, a small group of scientists, local clinicians, and community members came together to inform the creation of a dynamic transmission model for one Nunavik village that was most heavily affected by the outbreak. We built the model to be Nunavik specific-- to reflect unique demographics, social interactions (such as frequent inter-generational interactions), and the specific public health measures applied. The model predicts incidence, hospitalizations, and deaths. The collaborative modelling work is one way to increase community participation and leadership in covid-19 related policymaking, and can also provide community health committees with additional advocacy tools (modeling results) that they have helped create. Community participation in modeling increases legitimacy of key parameters that would otherise be impossible to make assumptions around. We are applying for funding to strengthen our modeling approaches and to be able to expand this work to other communities.",,-99,Research Institute of the McGill University Health Centre,195796.94,Human Populations | Other,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Approaches to public health interventions | Community engagement,2021 +P25524,459286,COVID-19 Vaccine Responses among African Canadian Children with and without Sickle Cell Disease,"The primary purpose of this study is to generate information on the immune responses to the COVID-19 vaccines among African Canadian children with Sickle Cell Disease. Persons with Sickle Cell Disease have weakened immune systems due to lack of a functional spleen, which is required for proper immune function. They are known to be at increased risk of poor outcomes from COVID-19. In addition, current data suggest that African Canadians are disproportionately represented among COVID-19 cases and severe outcomes. The study will generate data for children less than 12 years of age for whom it is expected that vaccine will be available by Fall/Winter 2021/22. We will also determine the factors that might influence vaccine responses among the study population; these include existing medical conditions besides Sickle Cell Disease, socioeconomic and demographic factors. We plan to study 600 children who have received the COVID-19 vaccines, including children with and without Sickle Cell Disease. These children will be enrolled from multiple sites across Ontario over a period of 1 year. The project is facilitated by another that we are doing that determines the frequency of COVID-19 antibodies among African compared with non-African Canadians. Vaccinated children will be offered blood testing at 4 points over 12 months, in order to check the extent to which their immune systems respond to the vaccine. They will also be surveyed to determine the presence of adverse events following vaccination. To facilitate the project and actively engage the communities, we have established a community advisory group, consisting of persons from the African Canadian community. and Sickle Cell Disease organizations. Ultimately, the data derived will provide useful information for individual participants/families, persons without functional spleens and will contribute to enhancing confidence in the importance and value of the COVID-19 vaccines among racialized communities.",,-99,Hospital for Sick Children (Toronto),380275.22,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Adverse events associated with immunization | Characterisation of vaccine-induced immunity | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +P25525,448955,COVID-19 Vaccine Responses among African Canadians: Sustainability of Immune Responses and Safety Profiles.,"The purpose of this study is to generate information on the safety profiles and immune responses of the COVID-19 vaccines among African Canadians and other members from racialized communities in COVID-19 hot zones in Ontario. While all persons from these communities will be studied, the main focus is on African Canadians, given data suggesting that they are disproportionately represented among COVID-19 cases and severe outcomes. We will also determine the factors that might influence vaccine responses among the study population; these include existing medical conditions, socioeconomic and demographic factors. We plan to study 1000 persons who have received the COVID-19 vaccines, including African as well as non-African Canadians. These persons will be enrolled from sites in Ontario. The project is facilitated by another that we are doing that determines the frequency of COVID-19 antibodies among African compared with non-African Canadians. In addition to working with existing vaccine surveillance networks, we will be working closely with public health teams that are associated with each of the geographic areas from which we are enrolling persons. Vaccinated persons will be offered blood testing at 4 points over 12 months, in order to check the extent to which their immune systems respond to the vaccine. They will also be surveyed to determine the presence of adverse events following vaccination. To facilitate the project and actively engage the communities, we have established a community advisory group, consisting of persons from each of the main communities participating in the study. Ultimately, the data derived will provide useful information for individual participants and the population as a whole and will contribute to enhancing confidence in the importance and value of the vaccines among African Canadians and other members of racialized communities.",,-99,Hospital for Sick Children (Toronto),371799.38,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Adverse events associated with immunization | Characterisation of vaccine-induced immunity | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +P25530,473326,Investigating the Cardiac and Brain Impact of COVID-19 in Diverse Populations,"COVID-19 has impacted people of different ethnic and socio-economic class differently. In particular, certain ethnic groups have a higher rate of infection with COVID-19 and worse prognosis after infection. We are also learning that COVID-19 may result in permanent changes to the brain and heart. In 2013, we assembled a multiethnic cohort of over 2,600 adults from the Greater Toronto and Hamilton Area in a study called the Canadian Alliance for Healthy Hearts and Minds. Participants provided blood samples and underwent a magnetic resonance imaging (MRI) scan of the brain and heart. We are now re-contacting them and propose to ask them in-depth questions on COVID-19 infection and vaccination and invite some participants with COVID-19 and others without a history of infection for further testing, including measuring their thinking ability and memory and a repeat MRI of brain and heart. This repeat assessment focused on COVID-19 will enable us to better understand the impact of COVID-19 on thinking, the cardiovascular system, and brain.",,-99,McMaster University,76662.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P25536,465766,"Re-imagining long-term care: Analyzing the health, well-being and employment of care workers using linked data and intersectional approaches","The COVID-19 pandemic greatly affected long-term care in Canada, exposing gaps in the provision of care for a vulnerable aging population. Moreover, the pandemic revealed a lack of information collected about health care workers in nursing homes, demonstrating the sector's unpreparedness to grapple with the caregiving challenges for older adults. The health needs faced by older adults in long-term care (LTC) can be addressed by focusing on improving the quality of care provided by the healthcare workers and the facilities in which they work. Improving the lives of caregivers and their working conditions can enhance the essential care services and supports that residents rely on for survival and daily living. Approximately, 500,000 Canadians live in nursing and retirement homes, and over the next 15 years, the number of Canadians 75 years old and over is expected to double. There is a need to examine how we value older adults and the workers who care for them. LTC workers include healthcare aides, personal support workers, registered practical nurses and registered nurses. The workforce is greatly gendered, made up mainly of women. Some research reveals that women who identify as migrants and/or people of colour compose a large proportion of low-waged care workers. Low wages, few benefits, limited protections, and part-time work result in high job losses and staff shortages. During the pandemic, over 50% of LTC homes reported critical staffing shortages that reduced the quality of resident care and endangered workers' safety. Furthermore, the literature reveals care workers providing direct services to COVID-19 patients experienced higher levels of moral distress, anxiety, and depression. For the fellowship, I will use population health surveys, linked with immigrant and heath databases at Statistics Canada to examine the health and well-being of the LTC workforce, the impact of COVID-19 and the lasting consequences on their health.",,-99,"Statistics Canada (Ottawa, ON)",42302.59,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health workforce,2022 +P25537,473768,Improving Genomic Epidemiology Methodologies and Practice through Interdisciplinary Data Integration and Analysis.,"Infectious diseases as shown by the COVID-19 pandemic remain a serious threat. Genomic sequencing has revolutionized the detection and characterization of pathogens for surveillance and outbreak investigation, creating a new field of genomic epidemiology. During this ongoing pandemic, we have witnessed several gaps in establishing effective global responses that require coordinated action such as our ability to quickly adapt analytical methods to new pathogens and the ability to integrate several data sources to generate knowledge for enabling evidence-informed decision-making. In this proposed research, I aim to further this field of genomic epidemiology by developing advanced data analysis methods. Additionally, I aim to optimize these methods to be capable of adapting to datasets from various pathogens, saving time to develop again for every outbreak. Finally, I want to combine genomics and advanced data analysis (bioinformatics) to establish a method of integrating epidemiological, political, and other contextual information with genomic data to improve public health preventive measures. This project will develop a program using intersectoral genomic epidemiology to counter infectious diseases.",,-99,"Simon Fraser University (Burnaby, B.C.)",65793.1,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2022 +P25542,448912,Investigating the Post-Acute Sequelae of SARS-CoV-2 Infections: a Patient Oriented Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) Study,"Some COVID-19 patients who initially recover from the acute illness subsequently develop new or continued symptoms that last more than 3 months without another explanation. This is called ""Long Hauler Syndrome"" or ""Post-Acute Sequelae of SARS-CoV-2 infection (PASC)"". The Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN pronounced 'sedrin') has been collecting data on men and women with suspected and/or confirmed COVID-19 since the beginning of the pandemic (March 2020) in 50 Emergency Departments (EDs) from 8 Canadian provinces. These data include patient characteristics (e.g., age, sex, self-declared gender identity and ethnic background, ongoing illnesses, why they presented to the ED), what happened to them after the ED (sent home or admitted), survival after being treated in the hospital, and their quality of life at 1, 2 and 6 months after their ED visit. For this proposed study, we will adapt our data collection across 14 EDs in 8 provinces to add additional follow-up time points and gather additional follow-up information on patients suffering from PASC at 3, 6 and 12 months to better inform decision makers about the resources they need. We will also collect additional outcomes directly reported by the patients themselves to better document their access to healthcare after they leave the hospital. We will collect this additional data on patients who presented to the EDs and tested positive for COVID-19 and on patients who presented to the EDs with similar symptoms but were COVID negative when tested. This will allow us to compare and more precisely define what is PASC and which patients are at risk to suffer from PASC and what they need to recover from PASC. The results of this study will inform decision makers and clinicians about the needs of patients living with, and recovering from PASC after leaving the hospital.",,-99,Université Laval,397178.72,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25543,487684,Expanding the Patient-Oriented Research Capacity of the Canadian Emergency Department Rapid Response Network (CEDRRN) to Enable Patient-Centered Adaptive Platform Trials and Ensure Health Crisis Preparedness,"During the COVID-19 pandemic, Canada's research response did not have the adequate systems in place to save lives. The pandemic has shown that engaging patients in research is more relevant than ever, especially for marginalized patients who were the hardest hit. Climate change is also adding new challenges to caring for patients in the emergency department (ED). New research infrastructures to ensure better pandemic and climate change preparedness are needed. The United Kingdom (UK) demonstrated that a highly performing health system can embed research into practice using innovative 'platform trials'. Platform trial benefits include: (1) multiple emerging questions can be evaluated simultaneously; and (2) data that is already collected can be utilized to increase the likelihood that patients are randomized to treatments more likely to be beneficial. However, platform trials create new challenges about how to meaningfully involve patients in their planning and also about how to obtain consent. The Canadian Emergency Department Rapid Response Network (CEDRRN, pronounced ""sedrin"") was created during the pandemic as a multisite observational registry to respond to decision-maker and patient partner questions. Its Patient Engagement Committee (PEC) guided its research questions and methods. Building on the UK's experience, CEDRRN aims to pivot its research infrastructure including its PEC to support future platform trials in EM to better prepare for pandemics and climate change. The overarching aim of this project is to expand CEDRRN's patient-oriented research capacity to enable relevant and timely platform trials in Emergency Medicine (EM) to address pandemic and climate-mediated disaster preparedness. Its specific aims are: (1) Build patient-oriented research capacity in EM that is equitable, diverse and inclusive; (2) Identify patient-centered research priorities suitable for future ED platform trials; (3) Explore what consent models are acceptable to ED patients.",,-99,Université Laval,152075.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase) | Therapeutic trial design | Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure,2023 +P25547,495102,Middle East Respiratory Syndrome (MERS) seroprevalence in zoonotic reservoirs and in humans: implications for spillover risk and population underlying infection,"Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of global importance that is currently mainly transmitted to humans from camels, although it is still unclear how the pathogen spreads and infects individuals across time and geography. Understanding its epidemiologic characteristics via serology (e.g. blood tests that measure the level of antibodies) is key to producing accurate estimates of future animal-human transmission and in turn, implementing public health measures to prevent this risk of ""spillover"". Barriers to this understanding, however, include the lack of unified and timely serology data, as well as limited awareness of population immunity. To address these barriers, an innovative and continuously updated synthesis and analysis of MERS seroprevalence will be conducted, which will include both academic and non-academic sources. The results will also be visualized on an interactive data web platform. This unique and streamlined approach will in turn inform estimates of MERS prevalence, possible cross-immunity from prior infection/vaccination against COVID-19, and spillover risk, thus facilitating vital insights for use by policy, research and clinical decision-makers in an era of pandemic preparedness. The culmination of this MERS case study will centralize access to MERS serology data, illustrate the feasibility and structure of a unified serosurveillance system, and highlight the design of a tailored data platform for pandemic preparedness. Ultimately, these efforts will build crucial capacity to monitor coronaviruses and other emerging infectious disease threats on a global scale.",,-99,University of Calgary,73558.84,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Immunity | Disease surveillance & mapping | Characterisation of vaccine-induced immunity | Policy research and interventions,2023 +P25550,462594,Investigating the metabolic drivers of hyperinflammation during viral infection,"Successful host defense requires tight control of inflammation to mount an effective immune response while limiting damage to the host. Loss of such inflammatory control can result in ""cytokine storm"" - a pathological dysregulated immune response characterized by immune cell hyperactivity and mass production of inflammatory proteins (cytokines) that causes tissue damage. Mortality from most acute viral infections, including Ebola, hemorrhagic fevers, seasonal influenza, and more recently SARS-CoV-2, is rarely due to the pathogen (virus) itself, but rather to such hyperinflammation by the host's immune system, causing organ damage and subsequent failure. While we know that the immune cells become hyperactive and produce excessive cytokines, we do not know what cause this dysregulation at the first place. A hallmark of any immune response is the profound change in energy requirement. As a result, cellular metabolism has emerged as a fundamental regulator in tuning the degree and type of immune function. The central question we will investigate in this proposal is how does metabolism in the local tissue environment regulate the fate of the inflammatory response to viral infection? To answer this, we will characterize the differences in nutrient dynamics and metabolism in the local tissue between a dysregulated vs. controlled inflammatory response to viral infection. Results from this study may provide better treatment to prevent or reduce tissue damage following viral infections",,-99,McMaster University,814242.44,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Ebola virus disease | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2022 +P25554,460162,Improving the use of propensity score methods in health research,"Scientists frequently want to estimate the effects of treatments, interventions and exposures on patient outcomes (e.g., the effect of smoking on heart disease or the effects of Covid-19 vaccines on variants of Covid-19). However, treated or exposed subjects often differ systematically from untreated or unexposed subjects (e.g., smokers may have diets and exercise habits that differ from non-smokers). For this reason, advanced statistical methods must be used to account for these differences in characteristics, so that the true effect of the treatment or exposure can be estimated. One such statistical method is known as the propensity score. It allows for the comparison of subjects who resemble one another, apart from the treatment or exposure received. We will extend and improve methods based on the propensity score. This will allow the method to be applied in a wide variety of settings, including many that occur in health research.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",184919.35,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,,,2022 +P25556,478741,Illuminating the Dark RNA Virome through ultra-deep homology search,"SARS-CoV-2 has killed millions and cost the economy trillions. To pre-empt future pandemics, we will radically increase the sensitivity of the computational tools used to detect RNA viruses. Illuminating the full diversity of Earth's viruses directly supports Canadians' health by empowering a new generation of unbiased viral diagnostics; and indirectly through better viral surveillance across all facets of One Health (monitoring of crops, wildlife, and our environments for pathogens). At most 0.1% of Earth's viruses are known. Our ignorance is due to 1) inadequate sampling of Earth's biodiversity; and 2) poor computational sensitivity for detecting viruses. To overcome each of these limits, we propose combining two state-of-the-art technologies in a dual ultra-massive (Serratus) / ultra-sensitive (AlphaFold2) experiment. Serratus is a cloud-computing platform allowing us to analyze the global-collection of DNA/RNA sequencing data. Collectively public sequencing data gathered over the past 15 years captures 10M+ samples (60M+ gigabytes) at a cost of $10+ billion. Previously with Serratus we analyzed 5.4 million samples and discovered >130,000 new species of RNA viruses (only 15,000 were known previously). This was based on standard methods which have less than 50% sensitivity for detecting a novel virus, those we call Dark RNA viruses. To identify the missing 50% of Dark RNA viruses, we will deploy an AI tool called AlphaFold2 which enables vastly more sensitive protein structure analysis, albeit at ~10,000x the computational cost. Thus we ""deeply"" analyze 50,000 datasets to find examples of Dark RNA viruses, and in turn perform a ""broad"" re-analysis of all (now 8M+) public datasets. Illuminating the RNA virome has the potential to uncover viruses associated with human diseases long believed to have an infectious causes: (re)consider Parkinson's, Crohn's, arthritis, or cancers. The goal of this project is to catalyse a new generation infectious disease research.",,-99,University of Toronto,168764.09,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing | Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2023 +P25557,432527,A behavioural science approach to evaluate the prevalence and predictors of COVID-19-related mental health issues and maladaptive behavioural coping (MBC) to inform the development of strategies for tailored interventions,"COVID-19 will lead to an increase in mental health issues (e.g., depression, anxiety, post-traumatic stress disorder) and maladaptive behavioural coping (e.g., drinking alcohol, taking drugs, taking out our frustrations on loved ones). However, not everyone will be affected or affected in the same way. In order to ensure that the eight people are getting the services they need, we need to understand what kinds of mental health and maladaptive behavioural coping problems are occurring, who they are occurring in, and how best to engage these individuals in the care that is available. The proposed project will be an 'add-on' to an ongoing Canadian-led large international online study looking at the impacts of COVID-19 (The iCARE study: www.mbmc-cmcm.ca/covid19). It will see how people are feeling and coping with COVID-19, in a diverse group of Canadians (men, women, young, old) - using representative sampling, over the next several months. The 'mental health and maladaptive behavioural coping' module will be completed with the main iCARE survey 5 times between July 2020 and January 2021 (a total of 15,000 responses). The questions in the module were developed using behavioural science theory and are similar to those being used in other international studies, meaning that what is happening in Canada can be compared to what is happening in other countries. This project will provide information on the 'real-time' impacts of COVID-19 on mental health and how people are coping among Canadians over the coming months. More importantly, we will be able to understand who is most at risk, what kinds of support, treatments and services they need, and how best to engage them in the available services. This information will be passed on to the federal and provincial governments to help them develop better strategies to ""flatten the mental health curve"" and improve quality of life outcomes in Canadians negatively impacted by COVID-19.",,-99,CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur,146402.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25558,443210,COVID-19 Variant Supplement - A behavioural science approach to evaluate the prevalence and predictors of COVID-19-related mental health issues and maladaptive behavioural coping (MBC) to inform the development of strategies for tailored interventions,N/A,,-99,CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur,32924.87,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25564,458896,Exploring mechanisms of bystander T cell activation in off-target neuropathology during Zika virus infection,"Zika virus (ZIKV) is an emerging mosquito-borne and sexually transmitted virus. The most recent South American epidemic in 2015-2016 identified several devastating effects of ZIKV infections. These include the development of microcephaly in growing fetuses and paralysis in adults. ZIKV has become a continued health threat in Latin America, Africa, and Southeast Asia through both mosquito-borne and sexual transmission, but there are currently no vaccines or treatments. Normally, CD8+ T cells should target and kill ZIKV-infected cells while leaving healthy cells alone. In our mouse model of ZIKV infection, we identified CD8+ T cells that become highly activated and kill non-infected cells in the brain, resulting in paralysis. In this project, we will examine how these T cells become excessively activated and cause off-target neurological damage. Specifically, we will investigate how inflammation and metabolism in the brain influence CD8+ T cell activation and off-target killing. We will also assess the role of immune cells in the brain, called microglia, in creating these dangerous inflammatory conditions. After determining how these T cells are activated, we will investigate methods to treat and prevent CD8+ T cells from causing off-target brain damage during ZIKV infection. As CD8+ T cells are thought to cause damage in other neurological diseases, like multiple sclerosis, the mechanisms we discover may be applicable to other diseases. Thus, our research will uncover mechanisms of T cell-mediated neurological diseases and identify novel treatment strategies.",,-99,McMaster University,84625.02,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P25566,485649,Linking Knowledge to Action: Advocating for Vaccine Confidence and Trust (ACT) in Parc-Extension,"We propose this knowledge translation intervention as an extension to The Advocating for Vaccine Confidence and Trust (ACT) project co-led by McGill University in partnership with Afrique au Féminin. The ACT project provides community members in Parc-Extension, Montreal to narrate the social, economic, and political constraints of their lives that contribute to COVID-19 vaccine decision making.The findings from this project are not limited to vaccines but emphasize the barriers for residents in accessing all health and social services prior to the pandemic and to this present day. Our knowledge translation intervention will be developed using a social justice lens to hold team members accountable and to prevent further data extraction or distributive injustice experienced by the Parc-Extension community. Inspired by Armstrong, Waters et al. 's logic model and Boyko, Riley et al.'s framework for establishing knowledge translation activities, for our ACT project knowledge translation we aim to focus on: (1) co-creation of knowledge translation activities; (2) co-creation of processes through which knowledge is effectively accessible to Parc-Extension community stakeholders (e.g., community organizers, activists etc.); and (3) translating knowledge and implementing it to improve and facilitate evidence informed decision-making (EIDM) in the Parc-Extension community. Our translation event will have two phases. First, we will host a large community meeting 1 that will consist of community residents, clinicians, academics, activists, educators, and policy makers in Parc-Extension to discuss our findings from the ACT project. Our second phase will be dedicated to collaborating with organizations to provide them with communications and evidence summaries that serve their community work, ultimately improving living conditions in this equity-denied and immigrant-dense neighbourhood.",,-99,McGill University,4412.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2023 +P25567,491942,Application for 2024 CIHR NIF (ECR): Investigating the role of SARS-CoV-2 and MERS-CoV transcription regulatory sequence (TRS) in viral gene expression and virulence,"I started my first independent position in April 2021. It has been challenging to get up and running during the pandemic. I am looking forward to learning from my ECR colleagues and from senior PIs the secrets of running a successful lab. I am also looking forward to building my network and connecting with colleagues to create a support network for us ECRs, My laboratory studies highly pathogenic coronaviruses, such as MERS-CoV and SARS-CoV-2, and how these viruses negatively impact the human immune response. Specifically, we investigate virus replication using in vitro (cell lines and organoids) and in vivo models. We investigate innate immune responses in human cells upon infection with coronaviruses. We develop next generation vaccines and therapeutic that are broadly protective to prevent the emergence of novel coronaviruses with pandemic potential. My research falls under the mandates of CIHR's III.",,-99,University of Saskatchewan,1925.76,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity",2023 +P25568,493830,Characterizing bat interferon stimulated genes as novel next generation therapy against highly pathogenic coronaviruses,"Bat species are being increasingly recognized as reservoirs of emerging viruses such as coronaviruses (SARS-CoV, SARS-CoV-2, and MERS-CoV), filoviruses (Ebola and Marburg virus), and paramyxoviruses (Nipah and Hendra viruses), among others. Bats that are naturally or experimentally infected with these viruses do not demonstrate clinical signs of disease, whereas other mammals, such as humans develop severe disease. We and others have shown that bat species have evolved a refined antiviral response which is characterized by: (1) low and controlled pro-inflammatory response, and (2) a robust interferon (IFN) mediated antiviral response. Type I IFNs are the first line of defence against invading viruses and they enact their effect by upregulating antiviral interferon stimulated genes (ISGs). Based on our previous studies, we will mechanistically characterize potent bat ISGs and develop top ranked ISGs as novel antiviral therapy against bat derived highly pathogenic human betacoronaviruses (beta-CoVs), such as MERS-CoV and SARS-CoV-2. We hypothesize that bat species have evolved ISGs that potently restrict beta-CoV replication and are resistant to inactivation by viral proteins. We will stimulate the production of ISGs in novel bat cell lines and in vivo in five species of bats (Eptesicus fuscus, Carollia perspicillata, Pteropus alecto, Rousettus aegyptiacus, and Eidolon helvum) that are known to carry viruses with human infection potential. We will characterize the 'interferome' in these bat species using bulk RNA sequencing and identify top ranked antiviral genes. Finally, we will generate recombinant bat ISGs and package them using lipid nanoparticle (LNP) technology to assess their antiviral efficacy against SARS-CoV-2 and MERS-CoV in vitro and in vivo. As multiple beta-CoVs with zoonotic potential currently circulate in bats, it is critical that we develop novel antiviral therapies to prevent the next pandemic.",,-99,University of Saskatchewan,220676.51,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Animal and environmental research and research on diseases vectors | Therapeutics research, development and implementation",Animal source and routes of transmission | Pre-clinical studies,2023 +P25569,494272,Investigating the role of SARS-CoV-2 and MERS-CoV transcription regulatory sequence (TRS) in viral gene expression and virulence,"Betacoronavirus (beta-CoV) is one of four genera of coronaviruses (CoVs) that includes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV evolved in 2012 and continues to cause seasonal outbreaks in the Kingdom of Saudi Arabia (KSA), along with travel-related cases. MERS-CoV is listed by the World Health Organization (WHO) as a pandemic threat. SARS-CoV-2 emerged in December 2019 and has caused a global pandemic. MERS-CoV has a higher case fatality rate of approximately 35%, compared to a predicted 2.3% for SARS-CoV-2. Despite epidemiological data suggesting a higher death rate for MERS-CoV infections compared to SARS-CoV-2, little is known about why MERS-CoV is more lethal. CoV gene expression is mediated via viral promoters called transcription regulatory sequence (TRS). All CoV TRSs include a conserved 6-8 nucleotides core sequence (CS) plus variable 5-prime and 3-prime flanking sequences that drive viral gene expression, including expression of viral genes that inhibit antiviral innate and intrinsic host responses. We hypothesize that MERS-CoV and SARS-CoV-2 TRS differentially regulate viral gene expression, which in turn leads to differential inhibition of the type I IFN response by viral proteins. During this five-year study, we will identify differences in molecular markers of disease on infection with MERS-CoV and SARS-CoV-2. We will specifically focus on MERS-CoV and SARS-CoV-2 TRS and identify regions within these sequences that are directly responsible for differential inhibition of protective interferon (IFN) responses. Our study will establish a framework to study accessory proteins, immune response modulation, and viral TRS in CoVs that remain poorly characterized, such as SARS-CoV, porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and pre-emergent bat borne CoVs (BANAL-236, PDF-2180, and others).",,-99,University of Saskatchewan,73558.84,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P25575,465726,Understanding and leveraging the role of networks and network actors in the implementation of practice change innovations in Ontario's long term care homes,"Issues involving the introduction, learning and embracing of new knowledge, innovation or practice change in healthcare are critical as the innovation impacts the quality of service and care of patients. My work focuses on long-term care (LTC), a sector that has historically faced its own unique challenges in moving research knowledge into practice. LTC was the epicentre of the COVID-19 crisis in Ontario during the first 2 waves where at least 300 long-term care facilities had logged outbreaks and 7000 seniors had died in LTC homes from COVID-19, representing over 80% of all COVID-19 deaths in Canada. The proposed project co-developed with Perley Health will focus on identifying the relational aspects of knowledge uptake and application, in addition to the barriers and methods of overcoming barriers to the implementation of infection prevention and control guidelines in LTC homes during the COVID-19 pandemic through a social network analysis and knowledge translation lens. As part of Perley Health's Centre of Excellence Strategy, the development of a Knowledge Translation (KT) Hub was proposed in 2019. This hub aims to improve how knowledge and support is shared in the long-term care (LTC) sector. The HSI Fellow will support the organization by her direct involvement in the Hub's development, and through application of findings from her research. The proposed project is of great interest to Perley Health and its partners as it stands to contribute to: 1) the understanding of how to effectively utilize social networks to facilitate evidence-informed change in LTC; 2) generate knowledge on how social network analysis can be used to identify flexibility that can be built into networks and LTC organizations to allow for effective planning during uncertain or stressful times; 3) inform future research and health policy development in LTC communities in Ontario and across Canada; and 4) advance the practice and science of knowledge translation/implementation science.",,-99,"Perley Health (Ottawa, Ontario)",27291.49,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Infection prevention and control | Health Systems Research,Restriction measures to prevent secondary transmission in communities | Health service delivery,2022 +P25580,479045,Multigenerational caregiving at home for a relative with dementia amidst COVID-19: A qualitative multiple case study of the new immigrant South Asian experience,"South Asian multigenerational households have been reported to have increased potential for contracting and spreading the COVID-19 virus to vulnerable older family members. Public health measures (e.g., lockdowns) intended to protect older adults have had unintended consequences for those caring for a relative with dementia (RwD). Creating additional vulnerability is a hesitancy to reach out to community supports due to language barriers, cultural and religious beliefs, and stigma surrounding dementia. Our goals are to 1) gain an in-depth understanding of new immigrant, multigenerational, South Asian family caregiving (for a relative with dementia) amidst COVID-19, and 2) to inform future family-centred, healthcare interventions aimed at supporting equity-deserving families during times of crisis. To achieve these goals we will employ a qualitative multiple case study to 1) understand how and why caregiving experiences within multigenerational South Asian families originating from Pakistan, Bangladesh, India, and Sri Lanka were impacted by COVID-19; 2) understand how and why the intersections of ethnicity, gender (identities, roles, relations, institutionalized), age, religion, and culture influence the experience of caring for an RwD; 3) understand how structural, personal, and relational processes changed during COVID-19 and 4) how and why these changes influenced multigenerational family caregiving for an RwD. We will employ purposeful, criterion, and maximum variation sampling to generate data from semi-structured interviews and focus groups with South Asian family caregivers. We will examine secondary data sources including genograms and ecomaps to understand the family structure, roles, caregiving responsibilities, and available formal and informal resources to support their caregiving activities. We will gather and analyze key documents including provincial, regional, and local policies to understand the COVID-19 context in Ontario and the GTA.",,-99,McMaster University,368468.99,Human Populations,Asian,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P25581,448875,The McMaster Multi-Regional Hospital Coronavirus Registry (COREG): Extending a Rapid Research Platform to Inform the Clinical Management of COVID-19 'long haulers',"In March of 2020, we launched the McMaster Multi-Regional Hospital Coronavirus Registry (COREG https://www.coregontario.ca/), a unique COVID-19 platform that is collecting detailed data on laboratory confirmed COVID-19 hospital patients, in collaboration with the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). This platform has collected detailed data on COVID-19 positive patients (n=2000+) across 7 cohorting hospitals in Kitchener-Waterloo, Hamilton, and Niagara. The COREG platform has also recruited over 130 patients who survived hospitalisation for COVID-19 to participate in a longer-term study on functional recovery from COVID-19. The COREG functional recovery study is collecting detailed information on symptoms, functioning and health outcomes at 3-,6-, and 9-months after hospital discharge for patients who had serious COVID-19 illness. Funding for the COREG platform, originally supported by CIHR, expires in June 2021. In light of our preliminary findings suggesting that as many as 70% of our study participants report that COVID-19 continues to impact their everyday life, we propose to continue our study for another year while expanding its scope. We will continue recruiting patients, add a 12-month follow-up visit, and collect additional information on hospital readmission, vaccination status, as well as study the impact of the new variants of COVID-19 on short- and long-term patient outcomes. This information is critical for understanding how best to support patients with COVID-19 in their recovery process in the months and years to come.",,-99,McMaster University,395474.63,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25582,483946,"Extending a digital mobility cohort to understand risk factors and impacts of post-COVID conditions in community-living older adults: the Aging, Infection and Mobility (AIM) project","Many Canadians are still experiencing post-COVID conditions that affect their daily lives long after the initial infection. This is especially complicated for older adults with existing health problems and those from disadvantaged communities where there is a higher risk of COVID-19 and post-COVID conditions. Mobility is a key factor in healthy aging and disease prevention, and it is likely impacted by common symptoms of post-COVID conditions (e.g., fatigue, brain fog, breathlessness). Still, mobility has yet to be adequately addressed in research studying post-COVID conditions. The Aging, Infection, and Mobility (AIM) project seeks to determine why some people develop post-COVID conditions, and others do not, and to examine the long-term effects of COVID-19 on functional outcomes in older people. The project will build on an existing aging and wearable technology study of over 1200 older adults from Hamilton and Toronto, including those from low-income areas. Participants will contact the research team within 5 days of developing symptoms of infection and undergo a rapid COVID-19 test. The study will include telephone-administered questionnaires, post-infection interviews, and regular follow-ups, including mobility monitoring using a smartwatch (e.g., step counts, location via GPS) and in-person assessments of physical, mental, and social health over 2 years. Our goal is to understand the risk factors and impacts of post-COVID conditions in older adults and marginalized seniors. We will also examine the impact of recurrent infections and vaccination on post-COVID conditions and the health of older adults. The results of this study will answer critical questions about long-term effects and risk factors for post-COVID conditions in older people. We hope to use this information to improve policies, services, and support for older adults with post-COVID conditions and other infections that affect mobility.",,-99,McMaster University,220606.65,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2023 +P25583,494302,"Aging, Infection and Mobility (AIM): Using wearable technology to understand the long-term functional impact of COVID-19 in community-living older people","Many Canadians are still experiencing post-COVID conditions that affect their daily lives long after the initial infection. This is especially complicated for older adults with existing health problems and those from disadvantaged communities where there is a higher risk of COVID-19. Mobility is a key factor in healthy aging and disease prevention, and it is likely impacted by common symptoms of post-COVID conditions (e.g., fatigue, brain fog, breathlessness). Still, mobility has yet to be adequately addressed in research studying the long-term impacts of COVID-19. The Aging, Infection, and Mobility (AIM) project seeks to determine why some people develop post-COVID conditions, and others do not, and to examine the long-term effects of COVID-19 on functional outcomes in older people. The project will build on an existing aging and wearable technology study of over 1200 older adults from Hamilton and Toronto, including those from low-income areas. Participants will contact the research team within 5 days of developing symptoms of infection and undergo rapid COVID-19 testing. The study will include telephone-administered questionnaires, post-infection interviews, and regular follow-ups, including mobility monitoring using a smartwatch (e.g., step counts, location via GPS), and in-person assessments of physical, mental, and social health over 2 years. Our goal is to understand the risk factors and long-term impacts of COVID-19 in older adults and marginalized seniors. We will also examine the impact of recurrent infections and vaccination on recovery from COVID-19 and the health of older adults. The results of this study will answer critical questions about long-term effects of COVID-19 on the health and functioning of our aging population. We hope to use this information to improve policies, services, and supports to help older adults recover from COVID-19 and other respiratory infections that affect mobility.",,-99,McMaster University,73558.84,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures | Health Systems Research",Post acute and long term health consequences | Indirect health impacts | Health information systems,2023 +P25584,470348,De la perte de contrôle alimentaire au trouble d'accès hyperphagique: trajectoires évolutives et facteurs de risque.,"The context of the pandemic has highlighted the presence of significant difficulties around food, weight and mental health; adolescents and young adults have been particularly affected. Indeed, young people have reported a greater tendency to eat compulsively and to overeat in response to the stress of COVID-19. Compulsive eating or LOC-eating, which is characterized by a feeling of loss of control over food intake and the type of food consumed, affects one in four young people and can lead to binge eating disorder (BED). This is the most prevalent eating disorder and for which few resources are available. Thus, this study focuses on the evolution of young people who present with LOC-eating and will attempt to answer the following questions: << Who are the young people struggling with LOC-eating who will develop BED? What are their experiences and needs? What intervention targets would prevent the persistence of LOC-eating symptoms over time and the crystallization of AHD? A sample of adolescents (14-18 years) struggling with LOC-eating will be recruited and will respond to a battery of questionnaires at the beginning and end of the study, then to a short survey with abbreviated measures at six subsequent follow-ups. The data will be analyzed using statistical modeling methods. In addition, a subgroup of adolescents, representative of the different evolutionary trajectories, will be recruited for an individual interview to collect qualitative data surrounding LOC-eating episodes, document the needs of young people and the support services requested. This project will provide a better understanding of this problem, in addition to providing recommendations on the management of LOC-eating behaviors in young people.",,-99,Université Laval,304961.68,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25586,488446,Addressing Urgent Calls for Public Health Workforce Planning: Establishing and Implementing National Indicators to Profile and Monitor the Public Health Workforce in Canada,"The Chief Public Health Officer's Report on the State of Public Health in Canada 2021 calls for urgent attention toward public health workforce planning and capacity development given ongoing workforce burdens due to COVID-19 and other emerging public health crises. However, the lack of data and infrastructure prevents us from assessing and monitoring trends in the Canadian public health workforce. The overall goals of this project are to establish standardized public health workforce indicators and develop a data collection system to support assessment/profiling of the Canadian public health workforce. In our project we will develop indicators that can be used to understand the diverse characteristics, learning and organizational needs of the public health workforce. We will work together with national and provincial collaborators which include public health decision-makers and organizations to survey the public health workforce in Canada using the newly developed indicators. Findings from the study will be provided to policy and practice decision-makers to be used for human resource planning, recruitment, retention, and professional development decision-making to safeguard the public health system in efficiently responding to future public health crises.",,-99,McMaster University,295430.68,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2023 +P25587,430246,The reorganization of institutional and community services for people experiencing homelessness and the needs of people experiencing homelessness to deal with the COVID-19 pandemic,"Considering the containment measures adopted by the government, the restrictions in terms of gathering and movement, the closures of public spaces but also private spaces of a public nature such as shops, shopping centers, libraries, etc., the reality of people experiencing homelessness (PSI) has changed profoundly in recent weeks, as have intervention practices in this field. However, few studies are interested in understanding the impacts on organizations, services, stakeholders and the people concerned, as well as the adaptation mechanisms and strategies put in place. The objective of this study is therefore to understand this resilience of organizations, institutional and community stakeholders and people experiencing homelessness. By observing and comparing in the different regions of Quebec, the adaptations, the transformations put in place as well as the resistance encountered to respond to this pandemic, the project aims to document and circulate the responses offered in terms of intervention in the field of homelessness, the impacts of COVID on stakeholders and their practices in different intervention settings and on PSI in their routines and needs by contrasting on the dimensions of sex, gender, sexual orientation, age, type of homelessness experienced and associated personal difficulties (in particular mental health and drug use) By creating a Homelessness-COVID19 Observatory, this study aims to produce analyses focused on the use of the results by professionals and decision-makers, and a transfer of knowledge oriented towards sharing lessons learned here to better support elsewhere in order to support and strengthen the resilience of all in the context of this pandemic.",,-99,Université de Montréal,146728.57,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P25588,486489,Functional Interrogation of the Host Proteome during Viral Infection,"Viruses are a diverse family of pathogens known to infect all life forms on the planet. RNA viruses in particular have been the causative agents of several pandemics in recent history including the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the 2009 swine flu pandemic caused by the H1N1 influenza A virus, and many other public health emergencies such as the Ebola and Zika virus epidemics. Enteroviruses, a subgroup of the picornavirus family are a diverse class of RNA viruses (most notably poliovirus), that cause several diseases, ranging from encephalitis and paralysis to respiratory diseases. Several large outbreaks of non-polio enteroviruses in North America and Europe have caused great concern about future pandemics. To better understand the host response to these viruses, we analyzed the reprogramming of the cellular proteome in response to enterovirus D68 (EV-D68) infection, a clinically-relevant enterovirus with pandemic potential. To do so, we employed mass spectrometry (MS)-based proteomics, a powerful technology that allows for the quantitative analysis of protein level changes and identified novel proteins with significant expression level changes. Our current proposal will aim to characterize the role of these novel targets and investigate their mode of regulation during infection. We aim to uncover promising new targets which could form the basis of new antiviral therapeutics and increase our fundamental knowledge of host immunity.",,-99,McGill University,13021.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Other,,,,,,,,,Disease X | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P25589,448865,Mental Health during the COVID-19 Pandemic: An Ongoing Living Systematic Review of Mental Health Burden and Intervention Effectiveness to Inform Management Strategies During and Post-COVID-19,"There will be serious mental health implications from COVID-19 that extend beyond the pandemic for many people. Addressing mental health needs requires understanding the nature and extent of mental health ramifications and evidence on effectiveness of interventions that may be rapidly employed to prevent or address mental health concerns. Studies from COVID-19 are published rapidly, but many are of dubious quality. Thus, curation of this growing evidence base is urgently needed to provide practitioners and policy makers with clear, coherent evidence synthesis. Living systematic reviews are systematic reviews that are continually updated and provide ongoing access to results via online publication. They are logistically challenging, but provide value beyond conventional systematic reviews in situations where (1) important decisions need to be made; (2) uncertainty in existing evidence poses a barrier to decision-making; and (3) new evidence is emerging rapidly. Such a review is urgently needed to guide mental health care during and following COVID-19. Our research team has expertise in high-impact evidence synthesis research (https://www.depressd.ca/teammembers). Our protocol has been made public on the Open Science Framework (https://osf.io/96csg/). We have already sorted through over 150,000 citations from 10 databases, including two Chinese-language databases, reviewed over 46,000 unique citations, and identified over 100 eligible studies on changes in mental health symptoms and over 100 eligible trials of interventions. We have published initial evidence online (https://www.depressd.ca/covid-19-mental-health). We are working closely with Canadian government personnel to inform mental health strategy. Important evidence will be published in the months to come. It is crucial to maintain funding for this important project to incorporate the higher quality evidence that is beginning to be made available.",,-99,Research Institute of the McGill University Health Centre,174819.17,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +P25590,494268,"Recovering from the COVID-19 Pandemic, Informing Future Public Health Crises, and Building a Global Evidence Base for Mental Health Research: A Systematic Review of COVID-19-related Mental Health","What will the research be about? We will investigate (1) if mental health changed from before COVID-19 to during the pandemic and how much; (2) how mental health changed across different pandemic periods; and (3) if there were effective programs to help people maintain positive mental health during COVID-19. What will be our outcomes? First, we will compare mental health symptoms before and during the pandemic and at different pandemic periods to determine how much they changed. Second, will compare mental health of people who received COVID-19-related mental health treatments to similar people who did not receive treatment to see how effective different treatments were. We will assess all outcomes for the general population and subgroups (e.g., women, men, older adults, people from low-and-middle income countries, heath care workers). Who will be in the study? We will include data from studies conducted anywhere in the world that looked at mental health in people affected by COVID-19. From April 2020 to July 2023 we searched 10 English- and Chinese-language databases to find eligible studies. We reviewed over 161,000 studies and found over 500 eligible studies that reported how mental health symptoms changed and over 400 that examined mental health interventions. What will the research team do? We will extract relevant data from each eligible study. Then, we will use statistical methods to combine results from all studies and estimate overall changes and treatment effects. We will do this for the general population and for approximately 15 subgroups. How will people use the results? Our study represents the most comprehensive review of mental health in COVID-19 in the world. We will be able to provide evidence that scholars can use to better understand how people respond to infectious disease outbreaks or other major society-wide disasters. Governments and health care systems will use or results to develop mental health plans for future crises.",,-99,Research Institute of the McGill University Health Centre,73558.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25592,442403,"Optimizing the resilience to COVID-19 of long-term care facilities serving linguistic-cultural minorities in Manitoba, New Brunswick and Quebec: evaluation and co-construction of innovative approaches to optimize the social participation of families and caregivers in the challenges of potential outbreaks","In Canada, 81% of deaths from the first wave of COVID-19 occurred in long-term care facilities (LTCFs). Added to this heavy toll is the threat of a second wave, which has already begun in several jurisdictions. Public health measures that reduce contact with professionals, families and caregivers are walling in LTCFs. This particular context, which includes restricting visits, is deepening the isolation and loneliness of older adults (EAs), particularly in minority contexts. These collateral effects that make EAs vulnerable, and which were not anticipated in the response, are now being strongly experienced by LTCFs. This unique and alarming situation requires LTCFs to develop promising practices for the present and future outbreaks and to ensure the maintenance of social capital between EAs and their families and caregivers, as well as with staff, to break isolation and loneliness. In Quebec, one third of COVID-19 infections have affected healthcare staff. Long-term care homes, the quintessential setting for seasonal outbreaks (e.g., influenza), already operate with insufficient staff, exhausted and afraid of infection. The vast majority of long-term care homes do not integrate digital technologies optimally to support staff. No one was prepared for the challenge of COVID-19, but the innovations implemented to date indicate pockets of success, winning practices that our project will capitalize on, by focusing on linguistic-cultural minorities (English-speaking long-term care homes in Quebec and French-speaking long-term care homes in Manitoba and New Brunswick). Indeed, few initiatives concerning COVID-19 are reported for these populations and the situation could be more difficult for PAs in linguistic-cultural minority contexts who usually encounter challenges in accessing the health system. Given the very limited number of long-term care homes dedicated to these minority populations in the provinces, families and loved ones are often geographically far away, or even in other provinces of the country, digital solutions appear particularly relevant. Of the six strategic options, the project focuses on the presence of families (no. 6), as key partners in care and breaking loneliness. Subsidiarily, it involves components 2) prevention and 3) workforce. The goal of the project is to identify and implement best practices and promising policies and create a community of practice to mitigate the isolation and loneliness of PAs per and post COVID-19 to ensure safe and quality care in ELTCs.",,-99,Université de Saint-Boniface (Manitoba),113983.69,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2020 +P25594,448822,Mieux vaut prévenir que guérir : les arts comme véhicules de transfert et d'échange de connaissances (TEC) en santé publique dans un contexte de pandémie,"La crise de la COVID-19 a conduit tous les pays à adopter des mesures préventives strictes et coercitives. Dans ce contexte d'urgence, ces mesures ont été souvent déployées selon une approche descendante sans véritable concertation intersectorielle et adaptation aux réalités locales. La mise en place de ces mesures a engendré des impacts négatifs pour plusieurs communautés incluant les communautés autochtones. De plus, l'utilisation d'actions coercitives pour imposer le respect des mesures a pu susciter la peur et la méfiance à l'égard des autorités publiques. Face à ce constat, il est nécessaire de reconnaître l'apport du savoir expérientiel des communautés et de mettre en œuvre des approches innovantes qui valiseront les savoirs, l'engagement et la mobilisation communautaires. L'utilisation des arts et de la culture peut être une avenue prometteuse pour travailler en collaboration avec les communautés autochtones. Basées sur un processus de transfert de connaissances inspiré et porté par les communautés, les interventions associant les arts et la culture permettent d'intégrer des approches sensibles aux contextes locaux, adaptées aux réalités communautaires, créatives, dynamiques et flexibles. Enfin, les interventions développées à l'aide de l'art gagneraient en acceptabilité sociale et favoriseraient l' appropriation communautaire. Le but de ce projet est d'étudier la contribution des arts et de la culture dans l'amélioration des interventions préventives en contexte de pandémie. Les trois objectifs spécifiques sont : 1) réaliser une cartographie des intervenants artistiques et les pratiques culturelles et artistiques des communautés autochtones ciblées ; 2) développer et mettre en œuvre une intervention préventive pour limiter la transmission de la COVID-19 dans les communautés à l'aide d'un modèle de transfert de connaissances basé sur les arts; et 3) évaluer la mise en œuvre de l'intervention avec les communautés.",,-99,Université du Québec à Rimouski,102244.25,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement,2021 +P25595,460355,Mental health and accessibility to services in universities: is diversity a barrier?,"The COVID-19 pandemic has had a significant impact on the mental health of Canadians. Preliminary results from a previous study conducted by our team show a significant deterioration in the mental health of university students and employees. This is particularly true for people from the five designated groups (women, visible minorities, people with disabilities, Indigenous people, LGBTQIAP2S+) in a university setting. What explains this particularly deteriorated state of mental health for people from these targeted groups? Could access or lack of access to services, for reasons related to gender, culture, language, disabilities, income and knowledge of available services, be a factor in this worsening? This study focuses on the mental health of students and employees of the Université du Québec network in the context of a pandemic and aims to gradually achieve 4 general objectives: 1) Identify the impacts of COVID-19 on the mental health of people who identify with one or more of the five designated groups; 2) List the main mental health services available in the university environment in order to meet the needs of these people; 3) Determine the factors that facilitate or hinder their access to these services; 4) Prioritize the best support services to put in place to support their mental health. In order to achieve these objectives, action research in the form of a living laboratory is proposed. The knowledge resulting from the work will take the form of practical tools that can be used by partner environments, as well as an action plan to promote the mental health of people identifying with one or more of the five designated groups in the university environment.",,-99,Université du Québec à Chicoutimi,269220.39,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons | Indigenous People | Sexual and gender minorities | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25596,442932,Upstream determinants of effective COVID-19 response: tools development and application through a case study in British Columbia,"In the midst of an acute crisis, researchers and governments have properly focussed on responding urgently to a rapidly evolving situation. This has resulted in a focus on interventions, their implementation, and their effectiveness. But the diverse experience of many countries suggests to us that there are critical ""upstream"" factors that need to be better understood and planned for to increase the likelihood of more positive outcomes. We refer to these factors as the institutional, organizational, governance, and political dimensions of the response to COVID-19 or ""IOGP"" for short. The effectiveness of current and future responses to pandemics can be improved by learning about and documenting better and worse practices in relation to IOGP both retrospectively and prospectively in the current crisis. This proposal will support the development of tools for analyzing IOGP factors and their application in a case study linking IOGP factors to policy responses to COVID-19 in British Columbia. An interdisciplinary team of researchers at the University of British Columbia has formed to study how IOGP factors influence the effectiveness of jurisdictional responses to COVID-19 across Canada. We have launched an initial pilot study, developing a theoretical framework, methods and instruments for data collection including comparative timeline, organizational mapping, and key event interview guides. This project will support further development of the definitions, concepts, methods, and measures that can be used to study these upstream factors and their implementation in BC and other provinces with local partners. The results will be used to identify better and worse practices in relation to laws, regulations, organizations, and political and governance processes that improve pandemic response. Better practices can inform different contexts in Canada and globally.",,-99,University of British Columbia,89998.04,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +P25598,444792,Étude de l'éco-efficience du port de l'équipement de protection individuelle contre la COVID-19 dans les urgences pour un contexte post-pandémique,"Our team will assess the use of personal protective equipment, commonly referred to as PPE, which includes various possible combinations of procedural masks or respirators (e.g. N95), gowns, gloves, goggles or visors. PPE is worn by healthcare professionals for all contact with people potentially infected with COVID-19. It is an essential component of care in emergency rooms because it allows staff to protect themselves and their patients from contagion. As vaccination begins, it is important to consider its place in the future. Because while PPE protects, its widespread use during the pandemic has cost governments hundreds of millions of dollars and generated an underestimated ecological footprint. Using methods from multiple fields (clinical sciences, epidemiology, biostatistics, industrial engineering, accounting, health economics, mathematics, and environmental engineering), our team will evaluate and weigh the benefits, economic costs, and environmental impacts of PPE use against COVID-19. With robust data, it will be possible to determine where PPE should be in emergency care as the pandemic emerges in order to promote sustainable health and make optimal use of limited system resources.",,-99,CHU de Québec,127627.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2021 +P25600,425011,Gender and intervention in dependency in the context of a pandemic with people in situations of social insecurity,"This knowledge synthesis aims to guide the improvement of addiction practices in the context of a pandemic, taking into account a sex- and gender-based analysis of the various social and health needs of people in socially precarious situations. People in socially precarious situations who are confronted with problematic substance use face increased risks related to COVID-19 compared to the general population. Often struggling with chronic health conditions, these people are particularly at risk of facing serious consequences if they become infected while health instructions tend to be more difficult to apply to their living context. The experience of a pandemic can contribute to triggering or aggravating a psychosocial crisis in these people already facing concomitant mental disorders. The WHO emphasizes that the social consequences of COVID-19 hit women even harder (economic precariousness, single parenthood, violence, barriers to access to services, etc.). A scoping review will examine best practice guides and evaluative studies to identify gender-sensitive addiction interventions that can be recommended for people in socially precarious situations in the context of COVID-19. Also, approximately 30 individual interviews of 45 to 60 minutes will be conducted with key stakeholders in Quebec with professional expertise or experiential knowledge on the subject of study (decision-makers, practitioners and drug users). The knowledge synthesis will integrate the results of these two components in order to guide the co-production of recommendations with the team of this project which integrates researchers and knowledge users from the addiction and public health sectors.",,-99,Université de Sherbrooke,35530.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P25601,443193,COVID-19 Variant Supplement - Gender and addiction intervention in the context of a pandemic with people in socially precarious situations,"This knowledge synthesis aims to guide the improvement of addiction practices in the context of a pandemic, taking into account a sex- and gender-based analysis of the various social and health needs of people in socially precarious situations. People in socially precarious situations who are confronted with problematic substance use face increased risks related to COVID-19 compared to the general population. Often struggling with chronic health conditions, these people are particularly at risk of facing serious consequences if they become infected while health instructions tend to be more difficult to apply to their living context. The experience of a pandemic can contribute to triggering or aggravating a psychosocial crisis in these people already facing concomitant mental disorders. The WHO emphasizes that the social consequences of COVID-19 hit women even harder (economic precariousness, single parenthood, violence, barriers to access to services, etc.). A scoping review will examine best practice guides and evaluative studies to identify gender-sensitive addiction interventions that can be recommended for people in socially precarious situations in the context of COVID-19. Also, approximately 30 individual interviews of 45 to 60 minutes will be conducted with key stakeholders in Quebec with professional expertise or experiential knowledge on the subject of study (decision-makers, practitioners and drug users). The knowledge synthesis will integrate the results of these two components in order to guide the co-production of recommendations with the team of this project which integrates researchers and knowledge users from the addiction and public health sectors.",,-99,Université de Sherbrooke,39196.27,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25602,472917,Causes and consequences of anti-PEG antibodies,"The quick development of mRNA vaccines in response to the global SARS-CoV-2 pandemic has shown the promises of this technology. Now a manufacturing and regulatory precedent exists, it is likely that these technologies will become an important tool for future biomedical applications. Both mRNA vaccines currently approved are protein-free lipid nanoparticles stabilized with poly(ethylene glycol) (PEG), a water-soluble polymer forming a hydrophilic corona on the surface of the particle. Despite the absence of proteins in the vaccine, the incidence of anaphylactic shock in the population appears to be 2- to 5-fold higher than with traditional immunization strategies. This increased reactivity has been tentatively attributed to PEG, an ingredient that is shared with many pharmaceutical, cosmetic and processed foods products. Due to its non-peptidic nature, PEG is likely a T cell-independent antigen, a type of antigen for which reactivity remains poorly characterized. We will look, in animal models, at the determinants driving the immune response toward PEG, following exposure to various PEGylated systems. We will investigate how the physicochemical properties of the antigens influence immune response, but also look at which biological pathways are implicated. Importantly, reactivity toward PEG will be related to the efficacy of PEG containing medicines in animals. In brief, this research project will investigate how a chemical present in drugs and the environment can affect the reactivity toward pharmaceuticals, including mRNA-containing technologies. We will obtain a clearer understanding of how to prepare safer PEGylated pharmaceuticals and the factors driving the immune response toward PEG. Altogether, these advances will guide toward the design of safer drugs, and better clinical managements of patients with pre-existing antiPEG antibodies.",,-99,Université Laval,76662.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Vaccines research, development and implementation",Vaccine design and administration,2022 +P25603,478261,Causes and consequences of anti-PEG antibodies,"The quick development of mRNA vaccines in response to the global SARS-CoV-2 pandemic has shown the promises of this technology. Now a manufacturing and regulatory precedent exists, it is likely that these technologies will become an important tool for future biomedical applications. Both mRNA vaccines currently approved are protein-free lipid nanoparticles stabilized with poly(ethylene glycol) (PEG), a water-soluble polymer forming a hydrophilic corona on the surface of the particle. Despite the absence of proteins in the vaccine, the incidence of anaphylactic shock in the population appears to be 2- to 5-fold higher than with traditional immunization strategies. This increased reactivity has been tentatively attributed to PEG, an ingredient that is shared with many pharmaceutical, cosmetic and processed foods products. Due to its non-peptidic nature, PEG is likely a T cell-independent antigen, a type of antigen for which reactivity remains poorly characterized. We will look, in animal models, at the determinants driving the immune response toward PEG, following exposure to various PEGylated systems. We will investigate how the physicochemical properties of the antigens influence immune response, but also look at which biological pathways are implicated. Importantly, reactivity toward PEG will be related to the efficacy of PEG containing medicines in animals. In brief, this research project will investigate how a chemical present in drugs and the environment can affect the reactivity toward pharmaceuticals, including mRNA-containing technologies. We will obtain a clearer understanding of how to prepare safer PEGylated pharmaceuticals and the factors driving the immune response toward PEG. Altogether, these advances will guide toward the design of safer drugs, and better clinical managements of patients with pre-existing antiPEG antibodies.",,-99,Université Laval,652554.47,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Vaccines research, development and implementation",Vaccine design and administration,2023 +P25605,460285,Addressing child nutrition and development and education outcomes during the COVID-19 pandemic: a longitudinal cohort and randomized controlled trial,"The COVID-19 pandemic has disrupted routines and impacted child eating behaviours. Pre-pandemic data showed that poor child nutrition and eating behaviours are associated with worsened development and school outcomes. However, this relationship has not been examined during the pandemic. Child nutrition behaviours developed early in life persist into adulthood and they could be modifiable targets for early nutrition interventions. Research is needed to understand the ongoing impact of children's nutrition on their development and education outcomes during the pandemic and identify effective interventions to ameliorate the impact. We propose to use the TARGet Kids! longitudinal cohort study, with data already collected pre-pandemic and since April 2020 to understand the impact of children's eating behaviours, dietary intake, and food environment on their motor, cognitive, language, emotional and behavioural development, school readiness and academic achievement in young children aged 0-12 years in the Greater Toronto Area. We also plan to understand the roles socio-demographic factors play in these relationships. This study will also test a nutrition-focused virtual intervention, which will equip parents with the skills and resources they need to promote healthful child eating behaviours and improve the nutrition, development, and education outcomes in children. With repeated data collected before the pandemic and during the first 1.5 years of the pandemic and detailed socio-demographic data collected from a diverse population, our study will understand and monitor the impact of the COVID-19 pandemic on young children's development and education and identify effective interventions to ameliorate the impacts of the pandemic and support the recovery of Canadian children and families.",,-99,Hospital for Sick Children (Toronto),805626.14,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25606,473324,Mobilizing stakeholders to build trust in public health systems in post-pandemic West Africa,"""Trust"" might arguably be the most studied social phenomena in the wake of COVID-19. In times of public health crisis-such as the COVID-19 pandemic-tapping into personal and institutional trust at multiple scales is paramount to disseminating critical information, maintaining confidence in disease containment measures, and eliciting behavioral changes among the citizenry. Mistrust, on the other hand, can have the opposite effect and lead to weak response to the pandemic. Many studies in different parts of the world have shown that without aspects of institutional, interpersonal, and political trust, politicians and public health professionals and scientist struggle to convince people to follow recommendations and instructions related to COVID-19. While the renewed interest in trust is refreshing for societies in a pandemic recovery world, the value of trust during a pandemic lies not in its associated outcomes, but in something much more fundamental-and that is how we conserve or strengthen social and political trust where it exists and how do we build trust where it is found to be low. This research will use a combination of quantitative and participatory methods to explore and identify strategies for sustaining or building trust in public health institutions in sub-Saharan Africa (SSA), specifically Ghana, Guinea, and Liberia. Governments and public health institutions in SSA will be better positioned to effectively overcome the COVID-19 crisis and build inclusive and equitable recovery societies if they have the evidence necessary to repair, sustain, and build trust and political capital while strengthening the social contract between public health institutions and citizens.",,-99,"Queen's University (Kingston, Ontario)",76662.06,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2022 +P25608,459284,Characterization of first- and second-generation RNA vaccine immunogenicity against SARS-CoV-2 variants of concern in Canada,"RNA vaccines enabled the fastest response to the COVID-19 pandemic. However, it is not yet well-understood how first-generation vaccines made with the wild type spike antigen are able to act against SARS-CoV-2 variants of concern (VOC). Furthermore, second-generation COVID-19 vaccines are now in development in order to minimize the dose of RNA required and limit the associated side effects. The first Canada-made RNA vaccine is currently being tested in a Phase I clinical trial, which uses self-amplifying RNA (saRNA) and is produced by Precision NanoSystems Inc. (PNI). saRNA is a special type of messenger RNA (mRNA) which is able to replicate itself in a patient's cells. However, it is not yet defined how these different types of vaccines, including first-generation mRNA and second-generation saRNA COVID-19 vaccines, affect how long the immune response lasts. Furthermore, a marginalized group of patients have exhibited severe anaphylactic reactions to the RNA vaccines, which may be in part due to a sensitivity to one of the lipid components called poly(ethylene glycol) (PEG). In order to fill these research gaps, we will characterize the functionality of first-generation mRNA vaccines against SARS-CoV-2 VOC in Canada in collaboration with the Snutch laboratory at UBC, who leads the surveillance of mutations through the CanCOGeN-VirusSeq initiative. Then, we will investigate how the duration of immunity induced by mRNA and saRNA COVID-19 vaccines. Finally, we will identify whether RNA vaccine formulations without PEG are able to induce an equivalent immune response in collaboration with the Cullis lab at UBC. The results of this research will inform the activity against SARS-CoV-2 VOC for current and future COVID-19 vaccine candidates available in Canada. These studies will also generate knowledge regarding design of RNA vaccines, including the necessity of the PEG component, both for the ongoing COVID-19 pandemic and for future outbreaks.",,-99,University of British Columbia,195569.8,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P25611,473356,Optimization of next-generation RNA vaccines for pandemic preparedness,"Messenger RNA (mRNA) technology has revolutionized our ability to develop safe, effective vaccines in a short time frame and at a large scale. Although the mRNA vaccines have had an incredible impact on the COVID-19 pandemic, there is still room for improvement. For example, we now know that the side effects are directly proportional to the dose of RNA, which motivates minimizing the required dose. Furthermore, the duration of immunity of the current mRNA vaccines is relatively short lived, requiring boosters approximately every six months. Finally, a certain proportion of the population has anaphylactic reactions to certain vaccine components, including polyethylene glycol (PEG). In this research program, we aim to develop RNA vaccines that improve upon the current mRNA vaccines and would be rapidly deployable in the event of an outbreak or pandemic. Self-amplifying RNA (saRNA) is the next generation of mRNA and the focus of my research program; it is a special type of mRNA that is able to replicate once it gets into a cell and requires a much lower dose. Like mRNA, saRNA requires a formulation that protects it from degrading and delivers it safely and consistently into cells. We hypothesize that by optimizing lipid nanoparticle formulations, which are the current state of the art technology for administering mRNA, and the dosing interval, we can identify lead clinical candidates for more potent and safer RNA vaccines. First, we will optimize LNP formulations that more efficiently the target immune cells that make a robust vaccine response. We will also optimize the dosing regimen to enable creation of a stronger immune 'memory' and longer lasting protection. Finally, we will engineer new LNP formulations that do not contain PEG so that more of the population is eligible to receive RNA vaccines. These vaccines can be applied to outbreaks, including COVID, seasonal viruses such as influenza, and future pandemics and will improve the health of millions of Canadians.",,-99,University of British Columbia,76662.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Vaccine design and administration | Characterisation of vaccine-induced immunity,2022 +P25612,488941,Pursuing REduction in Fatigue After COVID-19 via Exercise and Rehabilitation (PREFACER). A randomized feasibility trial,"After recovering from the initial SARS-CoV-2 infection, many people experience a range of lingering symptoms, collectively known as 'Long COVID' or 'Post-COVID-19 Condition'. Over 1.4 million Canadians are currently battling this condition, and the number continues to rise. While there are more than 100 different reported symptoms, fatigue stands out as the most prevalent. This persistent fatigue often diminishes the quality of life, impacts daily functions, and hinders individuals from working and caring for themselves. Unfortunately, we don't yet have a specific rehabilitation method targeting this fatigue. Current strategies to help people with Long COVID often come from experts' opinions or observational data. We've recently reviewed 14 clinical trials that tried different rehabilitation methods for people with these post-COVID symptoms. None of them focused specifically on fatigue, the most reported symptom of all. We also recognized that there was a high level of uncertainty around potential adverse outcomes from these interventions, further emphasizing the need for more focused research. Our study aims to explore the feasibility of a structured rehabilitation program to manage and potentially reduce post-COVID fatigue, thereby enhancing the overall quality of life. Patients will be recruited at the Post-Acute COVID Rehab Program at Parkwood Institute and will be randomized to a personalized rehabilitation program or a standard of care group. The experimental group will receive an 8-week personalized rehabilitation program. For this feasibility study, an initial sample of 60 participants will be randomly assigned to one of the two groups and will be followed for 24-weeks. With this feasibility study, we aim to pave the way for a definitive study targeting the most debilitating symptom of Long COVID, setting the groundwork for a future where post-COVID fatigue is effectively managed and treated.",,-99,University of Western Ontario,95663.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P25613,486573,Housing Policy and Mental Health During the COVID-19 Pandemic: A Comparative Analysis of Vancouver and Toronto,"By reducing the burden of economic uncertainty, regions that had strong pre-existing state social support prior to the pandemic, and that responded to the pandemic with new social policies, saw improved population mental health. Housing is a key social policy area that had an important impact on whether people followed public health orders during the pandemic. The characteristics of a person's home - whether it is in good repair, overcrowded, rented, or free from domestic violence - also have impacts on their mental health. Leading up to the pandemic, housing affordability has been a major issue in many Canadian cities, resulting in further stress during the pandemic. This has especially been the case in Vancouver and Toronto - two of the country's most expensive cities. In immediate response to the pandemic, many Canadian jurisdictions implemented eviction moratoria, rent freezes, and other measures to make sure people were able to maintain their housing; however, it is unclear the extent to which any of these housing policies considered mental health or the impact of stable housing on mental health. The objective of this research is to answer the following questions: 1. How did housing policies during the pandemic in Vancouver and Toronto consider mental health in their framing? 2. How did housing policy consider the unique needs of people living with mental health problems? To prepare for future public health or environmental crises, it is vital to determine how governments currently consider and approach mental health within housing policy, and what they might do to improve housing supports for people with mental illness.",,-99,University of Toronto,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P25615,448834,Role of antibodies in platelet response to SARS-CoV-2 and its variants,"Billions of platelets patrol blood vessels on the ready to prevent the loss of blood when a vessel is injured. The prevention of bleedings is the primarily recognized role of platelets, known since their first description in the late 19th century. When microbes such as a virus or its molecules enters the blood circulation, it generates multiple reactions such as fever, loss of blood pressure, alteration of heart rate and respiration. The virus that causes COVID-19 firstly infects the lungs. During COVID-19, there is obstruction of blood vessels by blood clots. With their abundance in blood, platelets are chiefly positioned to interact with viruses in blood. How platelets mediate the blood vessel obstructions in COVID-19 is however unknown. Our work has revealed that platelets are activated in COVID-19 patients (Zaid et al. Circulation Research, 2020), which is consistent with accumulating evidence from other laboratories. Here, we will thus determine how platelets are affected by the virus. We will use very innovative technologies and compelling functional assays that we have developed to study platelets in response to the virus that causes COVID-19. We will study platelets in humans and mice, and will uncover how they can modulate the expression of inflammatory molecules in COVID- 19. Given that more and more people are immunized for the virus that causes COVID-19, we will moreover aim to understand how antibodies may either protect from, or promote, platelet activation in COVID-19 taking in consideration emerging variants. We will thus elucidate the interplay between platelets and the virus that causes COVID-19, thereby providing new therapeutic targets, informing on potency of variants to induce thrombosis, and improving safety of vaccination.",,-99,Université Laval,207906.21,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2021 +P25617,478442,Identification of innate immune pathways as targets for immunomodulatory therapy in herpes simplex virus encephalitis,"Infection of the brain by herpes simplex virus (HSV encephalitis) is a devastating disease associated with a mortality rate of 70% if left untreated. Even with specific antiviral therapy i.e., intravenous acyclovir, the mortality rate is still about 15% with most survivors remaining with neurological sequelae. We postulate that both virus replication in the brain and the resulting uncontrolled inflammation are responsible for such high mortality and morbidity. In the next 5 years, we will further study the types of cells responsible for the detrimental inflammation and evaluate compounds that can block the immune response in a timely manner using mouse models. In addition, we plan to set-up a more relevant experimental model for understanding the pathogenesis of HSV encephalitis using human brain 3D models derived from human stem cells (called organoids). At term, our research will benefit the management of HSV encephalitis but also potentially that of other brain viral diseases caused by West Nile virus and Zika virus.",,-99,CHU de Québec,618801.66,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models,2023 +P25619,475164,Long-Term Care Policies to Integrate National Standards: The LTC-PINs Project,"Long-term care homes (LTCHs) have been an underfunded sector in the Canadian healthcare system for decades. The COVID-19 pandemic further exacerbated these challenges, with added pressures of staffing shortages and negative stigma related to the homes, the staff and their leadership. There is a need to implement national standards for LTCHs to ensure the delivery of quality care. As a response to this need, the Health Standards Organization (HSO) established the Long-Term Care Technical Committee in 2020. Led by Dr. Samir Sinha, 32 Technical Committee members with expertise in long-term care (residents, family members, health care providers, researchers, etc.) came together to develop a National Long-Term Care Services Standard. Although this is a great step to ensure the delivery of safe and high-quality long-term care services, a better understanding of how these standards will be taken up in the LTCHs is needed. The goal of the LTC-PINs Project is to understand the experiences and perspective of LTCH administrative staff and those directly involved in policy development and implementation as they implement the National Long-Term Care Services Standard. Specifically, we want to know what they need to develop these required policies from a development, implementation and evaluative perspective in order to successfully implement the National Long-Term Care Services Standard. From this, our team will draft a policy and knowledge dissemination plan. We will then invite key stakeholders to a round-table research and policy workshop to discuss the draft policy. Recommendations will be formulated and the final policy will be available for LTCH use. The LTC-PINs Project is the first step along a much longer journey to restore trust and build a better future for LTCHs in Canada.",,-99,Conestoga College Institute of Technology & Advanced Learning (Kitchener),109461.45,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery | Health leadership and governance,2022 +P25622,485651,Down the Rabbit Hole: Scientists' real-life adventures in misinformation and social media during the COVID-19 pandemic,"A virologist, a psychologist and a molecular biologist walk into a bar...This free CIHR Café Scientifique public event features three health researchers active in public education and health policy during the COVID-19 pandemic. On Tuesday, October 17 at 7:30 PM (SK), join us live in-person or on Zoom to hear scientists' personal stories about their (mis)adventures promoting accurate public health information on social media, consulting with news media and health policy makes, and discovering the best strategies for spotting and defeating ""fake news"". This panel discussion will be followed by a Q&A session with our guest researchers Dr. Angela Rasmussen (VIDO, USask), Dr. Gordon Pennycook (URegina/Itahaca Univ) and Dr. Kyle Anderson (College of Medicine, USask). *Everyone* is welcome, from anywhere, at this hybrid Café Sci event! Register for FREE at Eventbrite, which includes a ticket for a complimentary non-alcoholic beverage (cash bar also available). The in-person event happens at Saskatoon's Underground Café (430 20th St. W.), which is actually ground level and fully accessible to those who use mobility aids. The Zoom broadcast will be close captioned. Details also available on https://www.facebook.com/CafeSciSaskatoon.",,-99,University of Saskatchewan,4412.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Communication,2023 +P25623,466242,Canadian Consortium of Clinical Trial Training (CANTRAIN) platform: enhancing career preparedness in RCT research targeting different audiences across the continuum,"COVID-19 pandemic has highlighted the importance for Canada to have the capacity to run large clinical trials and no longer be only reactive but responsive in leading with increase capacity and quality. We are responding and proposing to create the The Canadian Consortium of Clinical Trial Training (CANTRAIN) Platform, a 9- province consortium to address the critical need for training clinical trial highly qualified personnel to fill the gap that presently exists across our public institutions and biotechnology industries. The overarching goals are to HARMONIZE, ENHANCE, INNOVATE, and SUSTAIN the quality and capacity of clinical research professionals, clinical trialists and coalition partners through an accessible platform co-created from multi-jurisdictional and multi-institutional collaborations. CANTRAIN will cater to different learner profiles a) trial to operations for clinical research professionals; b) design and analysis for clinicians and methodologists; and c) a stream dedicated to training various coalition-partners such as patients, indigenous community and equity-seeking groups, patient organizations, decision and policy makers, and science journalist and social media reporters. Across the streams, we will focus on EDI and sex-gender with progress-plus considerations. CANTRAIN includes EDI mentors, patient partners and knowledge mobilizer, enhancing our ability to break down barriers and build a larger, more diverse workforce critical to high quality and efficient clinical trial research. CANTRAIN adopts an equitable, diversified and inclusive collaborative approach at a National level (East, West, and Maritime provinces), achieving a Pan-Canadian team for clinical trial training, mentoring and networking. CANTRAIN will be flexible to facilitate multi-institutional expertise, mentorship engaging with diverse communities such as First Nations and practice-based settings, with respect of the Canadian diversity.",,-99,Research Institute of the McGill University Health Centre,8414219.07,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2022 +P25624,481151,Canadian Consortium of Clinical Trial Training (CANTRAIN) platform: enhancing career preparedness in RCT research targeting different audiences across the continuum,"COVID-19 pandemic has highlighted the importance for Canada to have the capacity to run large clinical trials and no longer be only reactive but responsive in leading with increase capacity and quality. We are responding and proposing to create the The Canadian Consortium of Clinical Trial Training (CANTRAIN) Platform, a 9- province consortium to address the critical need for training clinical trial highly qualified personnel to fill the gap that presently exists across our public institutions and biotechnology industries. The overarching goals are to HARMONIZE, ENHANCE, INNOVATE, and SUSTAIN the quality and capacity of clinical research professionals, clinical trialists and coalition partners through an accessible platform co-created from multi-jurisdictional and multi-institutional collaborations. CANTRAIN will cater to different learner profiles a) trial to operations for clinical research professionals; b) design and analysis for clinicians and methodologists; and c) a stream dedicated to training various coalition-partners such as patients, indigenous community and equity-seeking groups, patient organizations, decision and policy makers, and science journalist and social media reporters. Across the streams, we will focus on EDI and sex-gender with progress-plus considerations. CANTRAIN includes EDI mentors, patient partners and knowledge mobilizer, enhancing our ability to break down barriers and build a larger, more diverse workforce critical to high quality and efficient clinical trial research. CANTRAIN adopts an equitable, diversified and inclusive collaborative approach at a National level (East, West, and Maritime provinces), achieving a Pan-Canadian team for clinical trial training, mentoring and networking. CANTRAIN will be flexible to facilitate multi-institutional expertise, mentorship engaging with diverse communities such as First Nations and practice-based settings, with respect of the Canadian diversity.",,-99,Research Institute of the McGill University Health Centre,2193099.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2022 +P25625,460301,"Addressing the Harms of COVID-19 on the Health of the Canadian Health Workforce: Evaluation of an Evidence-Informed, Multi-Level Intervention Strategy","The COVID-19 pandemic has had an enormous impact on the mental heath of health workers with significantly rising levels of distress and burnout at work. The combined impacts of the growing health care needs of the population - both those suffering from COVID-19 and those experiencing delays in care as a result of increased burden on the healthcare system during the pandemic, combined with the growing exodus of health workers from the health care system has created a critical and unsustainable situation requiring immediate intervention. Based on the timely research our team has conducted on the causes of health worker burnout during the pandemic, we have created a toolkit of evidence-based strategies to address rising rates and improve overall mental health. For this project, we intend to evaluate the different elements of this toolkit that will be implemented at the individual, organizational, and system/policy levels to enable further refinement and improvements. Ultimately, we hope a wide range of health care settings and organizations will adopt this toolkit to improve health workers' mental health, which has declined significantly during the pandemic.",,-99,University of Ottawa,402976.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +P25629,459246,Prioritization of intensive care in an extreme pandemic context: 1) modeling/simulation of different strategies for prioritizing access to intensive care and 2) democratic deliberations of stakeholders on the values ​​underlying the models and their health impacts.,"Faced with a potential shortage, one of the strategies considered in this COVID-19 pandemic has been the development of triage (or prioritization) protocols for access to intensive care. Quebec and Ontario have each designed an adult prioritization protocol for access to intensive care in an extreme pandemic context that aims to allocate resources to reduce mortality while being fair and equitable. Fortunately, neither of these protocols has ever been implemented. Consequently, we do not have data on the impacts that their implementation would have had. We also do not know what the population thinks of them. These protocols have not been the subject of a formal public consultation process. What do the people targeted by the protocol say? This project aims to carry out: 1) a mathematical modeling/simulation of two prioritization strategies (application of the adult protocol and the first-come, first-served principle) for comparative purposes; 2) democratic deliberations with members of the public based on the results of the modeling of the two prioritization strategies and on the values ​​underlying them. Simulating different prioritization strategies will generate objective data on their health impacts (number of lives saved). Submitting the content of the protocols to deliberation will allow for informed feedback from the public in order to bring out the most optimal model.",,-99,Université de Montréal,165175.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25633,494279,Humoral and cellular immune responses to COVID-19 vaccination and infection in older adults.,"Older adults have born the brunt of the COVID-19 pandemic. Despite having high vaccination rates, they are still the most likely to become infected, hospitalized, and die of COVID-19. Although it is tempting to see this as a failure of our current vaccines, the COVID-19 mRNA vaccines far outperformed vaccines for influenza or pneumonia in reducing infections and deaths in older adults. We have learned a lot about the types of immune responses these vaccines generate but, surprisingly, we still don't really understand why some older and frail adults are protected while others are not. Studies from other types of vaccines find that the immune responses that protect younger adults are not necessarily the same as those that protect older adults. We aim to figure this out using over 10,000 samples that we have collected from the ""COVID-19 in LTC study"". In this study we had over 1000 people from 26 different retirement homes and long-term care homes give blood about every three months between March 2021-December 2023. Because we know what kinds of health conditions and medications people had, as well when people got infected, we can uncover the role of medications and health conditions and determine what kinds of immune responses protect from infection and which don't. One of the aims of this proposal is to investigate different types of antibodies including antibodies that stimulate immune cells to kill virus infected cells, antibodies that stop the virus from getting into cells, and antibodies that are thought to lead to less inflammatory immune responses. Because we know who did and did not get infected, we can investigate which of these are protective. We have also discovered some counter-intuitive findings where instead of protecting people from infections, sometimes having an omicron infection makes them more likely to get another infection. We need to understand why this is so we can prevent infections and tailor vaccine schedules to protect our most vulnerable.",,-99,McMaster University,73558.84,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P25638,464066,An intersectional investigation of women's experiences of overlapping overdose and COVID-19 public health crises,"British Columbia (BC) continues to grapple with an overdose epidemic that has largely been framed as a men's public health crisis. Little has been said regarding how women (transgender, Two-Spirit and non-binary inclusive) are impacted, or how they might be differently navigating overdose risk environments or access to life-saving health services. Despite the implementation of a range of overdose prevention interventions, rising death rates in BC are compounded by the global COVID-19 pandemic, rendering the overdose epidemic a pressing public health issue. Some sub-populations of women are not fully benefiting from current interventions, illustrating the need to better examine why. Women, in dynamic relationship with race, class and sexuality, are disproportionately impacted by social violence, which shapes health and overdose risk as well as access to and uptake of overdose prevention interventions. Emerging evidence indicates that women are more negatively impacted by the COVID-19 pandemic than men, exacerbating existing health inequities. Building upon our extensive experience in examining risk, harm, and health care access among women who use drugs, we are requesting funds to support a 4-year qualitative study addressing the following objectives: 1.To examine how intersecting social, structural, and environmental forces (including violence and COVID-19), shape women's overdose risk environments and contribute to inequities in health outcomes; 2.To examine the implementation of interventions to address overlapping overdose and COVID-19 health crises, including policy recommendations, and their impacts on health-related outcomes; 3.To explore the experiences of women who use drugs in: the mitigation of overdose-related risk during the COVID-19 pandemic; engagement with overdose- and COVID-19-focused interventions; as well as, factors that facilitate or impede their meaningful engagement in these activities during dual public health emergencies.",,-99,University of British Columbia,193867.06,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Approaches to public health interventions,2022 +P25639,461389,An intersectional investigation of women's experiences of overlapping overdose and COVID-19 public health crises,"British Columbia (BC) continues to grapple with an overdose epidemic that has largely been framed as a men's public health crisis. Little has been said regarding how women (transgender, Two-Spirit and non-binary inclusive) are impacted, or how they might be differently navigating overdose risk environments or access to life-saving health services. Despite the implementation of a range of overdose prevention interventions, rising death rates in BC render the overdose epidemic a pressing public health issue compounded by the COVID-19 pandemic. Some sub-populations of marginalized women are not fully benefiting from current interventions, illustrating the need to better examine why. Women, in dynamic relationship with race, class and sexuality, are disproportionately impacted by social violence, which shapes health and overdose risk as well as access to and uptake of overdose prevention interventions. Emerging evidence indicates that women are more negatively impacted by the COVID-19 pandemic than men, exacerbating existing health inequities. Building upon our extensive experience in examining risk, harm, and health care access among women who use drugs, we are requesting funds to support a 4-year qualitative study addressing the following objectives: 1. To examine how intersecting social, structural, and environmental forces (including COVID-19) produce violence, shape women's overdose risk environments and contribute to differential outcomes across drug-using populations; 2. To examine the implementation of interventions to address overdose and COVID-19 health crises, including policy recommendations and their impacts on health-related outcomes; 3. To explore the experiences of women who use drugs in: the mitigation of overdose-related risk during the COVID-19 pandemic; engagement with overdose- and COVID-19-focused interventions; as well as factors that facilitate or impede their meaningful engagement in these activities during dual public health emergencies.",,-99,University of British Columbia,387734.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2022 +P25642,460727,Réponse aux besoins importants de santé mentale : Poursuivre l'évaluation des retombées du modèle Recovery College,"Our societies are facing significant mental health challenges, accentuated by the Covid-19 (C-19) pandemic. While all citizens are affected, large segments of the population, such as women, students, people of gender diversity, health workers and people with mental or chronic illnesses, are at greater risk of experiencing a deterioration in their mental health. To mitigate these risks and strengthen protective factors, innovative strategies for the prevention and promotion of mental health have had to be implemented. For the past two years, in response to the C-19 context, our team has adapted and evaluated a mental health education intervention based on the Recovery College (RC) model, adapted to a brief, online intervention. Initially implemented in England, and since then in more than twenty countries, the RC model promotes an educational approach in the community where everyone has free access to training on well-being and mental health. The results of the pilot study support positive impacts on the mental health of all groups of participants: women, students, health service providers, people with mental or chronic illness, caregivers, as well as members of the general population. The objective of the study is to continue the evaluation of these impacts with a larger sample of learners, to identify the impacts according to the different groups of learners and according to the number of training courses followed. The adaptation of the RC model leads to benefits for the different groups of learners. It is important to continue its evaluation, in order to demonstrate that this brief intervention can make a difference in the protection and deterioration of the mental health of the population.",,-99,Université du Québec à Trois-Rivières,307203.95,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25643,442982,Living network meta-analysis and rapid recommendations for the treatment of COVID-19,"Patients and clinician worldwide need trustworthy, rapidly updated guidelines to inform their treatment of patients with COVID-19. Trustworthy guidelines need trustworthy evidence summaries. These summaries need to be up to date and need to differentiate well done studies producing valid results from poorly done studies that are likely to be misleading. The evidence needs to be interpreted properly by considering all the relevant studies addressing each treatment, including their strengths and limitations. In addition, it is important to revise evidence summaries frequently as new information is published. We have created trustworthy summaries of the evidence that we update continually as new studies are published. We search many databases to detect all relevant trials including COVID-19 patients. We evaluate design and conduct of the studies to separate the more and less valid. We also combine the results from all of studies in a single analysis that allows patients and doctors to compare all treatment options. These optimal evidence summaries inform trustworthy practice guidelines. We create trustworthy guidelines by constituting a panel that includes experts in COVID-19, experts in assessing evidence, front-line clinicians treating COVID-19, and patients who have lived experience of COVID-19. Panel members are free of conflict of interest. These recommendations are produced quickly and revised constantly as researchers publish new data. Finally, we publish our summaries and recommendations in websites that are freely available to all. The work is conducted in collaboration with a leading medical journal, the British Medical Journal, and is published there. The work is also conducted in collaboration with the World Health Organization, and are published as WHO guidelines. The pandemic will not be over soon. We will continue producing and updating these evidence summaries and recommendations using the large amount of new evidence that is published every day.",,-99,McMaster University,1036429.01,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Hospital personnel | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health leadership and governance,2020 +P25645,480681,Estimation of SARS-CoV-2 infection rates using phylogenetic summary statistics.,"SARS-CoV-2 infection is confirmed via a nose or mouth swab test. While accurate for identifying individual cases, this testing method has underestimated the total number of SARS-CoV-2 cases, due in part to frequent symptomless infections which can go untested. Additionally, with inequitable access to testing, some communities have significantly inferior case reporting than others. Since SARS-COV-2 case counts inform public health measures, an accurate estimate benefits all communities. To date, researchers have attempted to estimate the actual number of SARS-CoV-2 infections using two methods. The first method utilizes antibody testing to compare the number of individuals with markers of SARS-COV-2 infection in their blood to case counts. Unfortunately, this method can be subject to sampling bias and is becoming ineffective with increasing vaccinations which results in antibody creation in the vaccine recipient. The second method fits models of pandemic spread to SARS-CoV-2 case count data, which can oversimplify virus spread and lead to inaccurate estimates. Seeking to enhance infection estimation accuracy, we will utilize the SARS-COV-2 evolutionary history reconstructed from genetic sequences that are already generated. Using computer simulations, our goal is to find a link between features of a tree which represents how infections are related to each other (i.e. the shape of the tree) and infection numbers. Subsequently we will develop a computer program to estimate SARS-COV-2 infection numbers based upon features of the tree. Enhanced accuracy of infection estimates will provide vital information to support public health measures in the ongoing SARS-COV-2 pandemic by providing a more accurate representation of the true number of infected individuals.",,-99,University of Western Ontario,13724.56,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P25647,474616,Careful Ventilation in Acute Respiratory Distress Syndrome. The CAVIARDS study,"Each year almost 40,000 Canadians receive mechanical ventilation for a a diffuse inflammation of the lung caused by bacterial infection, flu or trauma and called acute respiratory distress syndrome (ARDS). The most recent and specific cause of admission to an ICU has been COVID-19 which caused hundreds thousand cases in Canada. As shown by the pandemic, mortality under mechanical ventilation is still unacceptably high, often >40% : clinicians are still struggling about the best way to deliver mechanical ventilation. We think the prognosis can be improved by making ventilation more protective for the lung. Mechanical Ventilation is indeed life-saving but, paradoxically, can cause further inflammation and damage in the remaining healthy lung and in the whole body. Current mechanical ventilation is often not sufficiently lung protective. We think that the use of bedside measurements that we previously described can make ventilation less injurious, safer and that it will improve survival. Positive pressure is one of the cornerstone of the treatment but we propose to adjust it based of the individual lung response to pressure using a technique that we designed: this differentiate responders to high pressure vs. non responders. For the first time, pressure applied with mechanical ventilation will be individualized. We also showed how to monitor and control the degree of spontaneous ventilation in conjonction with the ventilator and which should be facilitated for the patient. We believe that these measures are not ony feasible but can guide the ventilatory management and improves the outcome of patients under mechanical ventilation. We have designed two studies, one for COVID-19 patients and one for the other forms of ARDS that are usally seen out of a pandemic. The study about COVID-19 patients is almost completed and we have been able to start the non-COVID study but we need additional funding to complete this 2nd study.",,-99,Unity Health Toronto,163135.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2022 +P25648,474598,Careful Ventilation in Acute Respiratory Distress Syndrome. The CAVIARDS study,"Each year almost 40,000 Canadians receive mechanical ventilation for a a diffuse inflammation of the lung caused by bacterial infection, flu or trauma and called acute respiratory distress syndrome (ARDS). The most recent and specific cause of admission to an ICU has been COVID-19 which caused hundreds thousand cases in Canada. As shown by the pandemic, mortality under mechanical ventilation is still unacceptably high, often >40% : clinicians are still struggling about the best way to deliver mechanical ventilation. We think the prognosis can be improved by making ventilation more protective for the lung. Mechanical Ventilation is indeed life-saving but, paradoxically, can cause further inflammation and damage in the remaining healthy lung and in the whole body. Current mechanical ventilation is often not sufficiently lung protective. We think that the use of bedside measurements that we previously described can make ventilation less injurious, safer and that it will improve survival. Positive pressure is one of the cornerstone of the treatment but we propose to adjust it based of the individual lung response to pressure using a technique that we designed: this differentiate responders to high pressure vs. non responders. For the first time, pressure applied with mechanical ventilation will be individualized. We also showed how to monitor and control the degree of spontaneous ventilation in conjonction with the ventilator and which should be facilitated for the patient. We believe that these measures are not ony feasible but can guide the ventilatory management and improves the outcome of patients under mechanical ventilation. We have designed two studies, one for COVID-19 patients and one for the other forms of ARDS that are usally seen out of a pandemic. The study about COVID-19 patients is almost completed and we have been able to start the non-COVID study but we need additional funding to complete this 2nd study.",,-99,Unity Health Toronto,652540.21,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2022 +P25649,460305,"Gambling, Problem Gambling and the COVID-19 Pandemic: The Experience of LGBTQIA2S+ People","Gambling (Gambling) plays a major role in the consumption habits of the population, both in Canada and abroad. The COVID-19 pandemic has had major repercussions on the practice of gambling (shift towards online gambling, increase in the practice of gambling among certain at-risk groups, etc.). However, we know very little about the gambling habits and the experience of health care and social services during the pandemic of certain marginalized groups such as people identifying as sexual and gender diverse (i.e. LGBTQIA2S+). This situation is worrying since LGBTQIA2S+ people are at greater risk of presenting problematic gambling. This study aims to describe the impacts of the COVID-19 pandemic on the practice of gambling and problem gambling among LGBTQIA2S+ people, understand the experience and lived experience of LGBTQIA2S+ people with problem gambling, and identify interventions deemed effective by LGBTQIA2S+ people with respect to problem gambling during the pandemic. Ultimately, this study will make it possible, based on evidence and the experience of individuals, to formulate avenues of action to improve interventions as well as health care and social services intended for LGTBQIA2S+ people with problem gambling and to reduce the harmful consequences associated with gambling within the LGBTQIA2S+ population in the event of a pandemic and/or future health emergency.",,-99,Université de Sherbrooke,237527.11,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",,2021 +P25653,459222,COVIGRO: Impact of COVID-19 and the SARS-CoV-2 vaccine on placental and fetal development,"The scientific data on the impact of COVID-19 on pregnancy are limited but suggest an increase in complications such as preterm birth and preeclampsia. At the same time, the scientific data are limited regarding the effectiveness of the COVID-19 vaccine given during pregnancy and whether gestational age can influence its effectiveness and/or impact on the outcome of the pregnancy. We will compare two cohorts of pregnant women, one recruited before the pandemic (2017-2018) and one recruited during the 2020-2021 pandemic. Using blood tests collected at different times during pregnancy, and using questionnaires, we will be able to establish whether the patient was infected with COVID-19 and whether she received the vaccine. We will evaluate the effect of COVID-19 on placental development and fetal development, as well as on the rate of complications. Finally, we will evaluate whether the vaccine received during pregnancy is as effective as the vaccine received before or after pregnancy.",,-99,Université Laval,211488.24,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Secondary impacts of disease, response & control measures",Adverse events associated with immunization | Characterisation of vaccine-induced immunity | Indirect health impacts,2021 +P25655,471937,Studying Viral Spike Proteins to Inform a Universal Coronavirus Vaccine,"Coronaviruses (CoVs) are critical to research since they can be detrimental to global health and have caused three major epidemics in humans in the last 20 years. While the current vaccines against SARS-CoV-2, the virus which causes COVID-19, are highly effective, they are not well-suited for the wide range of variation that different CoVs can have. To better address this ongoing threat to global health, our group aims to design a universal CoV vaccine which could protect against multiple CoV strains. While most of the original SARS-CoV-2 vaccines targeted one part of the viral spike protein, we hypothesize a universal vaccine will be more effective by targeting multiple, well-conserved sites on the viral spike that are present on a range of virus strains. Dr. Corbett's team is well poised to study CoV vaccines due to their role in the development of the Moderna mRNA COVID-19 vaccine. For my project, I will study the structure of the SARS-CoV-2 viral spike protein and the human immune response to the protein, with the goal of informing a universal CoV vaccine. Specifically, I will determine the best domains on the spike protein to target for vaccination by studying how different antibodies (from previously infected people) can inhibit virus infection. The antibodies will be tested in combination and individually to determine what yields the highest level of protection against different CoVs. The specific binding sites of the antibodies will then be visualized through high resolution imaging to map the important sites for vaccine targets on the spike protein. Using this knowledge, our group will design optimized vaccine platforms in the lab to elicit enhanced immune responses against these sites and improved vaccine efficacy. This work will be initially done in mice models, with the long-term goal of reaching clinical trials in humans. If successful, this cross-reactive vaccine strategy could also be applied to other viral pathogens with pandemic potential.",,-99,Harvard University (Massachusetts),109655.17,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Belize,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease pathogenesis | Pre-clinical studies | Vaccine design and administration",2022 +P25656,491104,Investigating the topology of viral surfaces to inform improved therapeutics & vaccines.,"Recently, COVID-19 demonstrated that scientists and governments can mobilize quickly to address viral pathogens. However, to be able to rapidly deploy effective antivirals and vaccines, a thorough understanding of virus biology is needed for virus families with the pandemic potential. Since coronaviruses (CoV) have shown a high potential to cause disease in humans, my research seeks to develop new understandings of CoV biology to inform improved treatment and prevention strategies. While SARS-CoV-2 has been well studied, endemic CoV which circulate in populations and cause 30% of annual colds, are less well studied. Improving our understanding of the early virus-to-cell interactions for endemic CoV may help propel vaccine and therapeutic Ab development since these interactions are the targets of potent antibody responses. To this end, in Phase 1 my project will identify key antibodies against the viral spike protein of endemic CoV to inform which targets are most effective to elicit in vaccination. These patient-derived antibodies will be tested in three different laboratory techniques (flow virometry, virus capture and virus neutralization) against the endemic CoV spike protein to develop a thorough understanding of how they perform in different experimental contexts. This project will also assess the role that human proteins on the surface of viruses may play in infection. Importantly, since my lab collaborates closely with industry to produce the Moderna SARS-CoV-2 vaccine, the likelihood that this work can have a translational outcome is high. After completing this work in Phase 1, in Phase 2 my lab will focus on innovating viral diagnostics using the powerful emerging technique flow virometry, and studying emerging viral pathogens to ensure pandemic preparedness. We will also have a strong focus on utilizing the known properties of viruses to seek novel answers for current challenges in agriculture and biotechnology.",,-99,Harvard University (Massachusetts),198239.44,Human Populations | Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Belize,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2023 +P25658,486635,Influence of intestinal permeability on the manifestations of long COVID-19,"SARS-CoV-2 infection causes acute respiratory and systemic disease COVID-19 and leads to cytokine storm. In addition to the lung, damages to the gut and gastrointestinal have also been reported during acute COVID-19. Long lasting symptoms after acute COVID-19 led to description of long-COVID, a syndrome encompassing a protracted course of physical and neurological symptoms that may persist up to 6 months. To date, only few biomarkers of long-COVID have been described. Previous studies showed that high circulating levels of beta-glucan (BDG) are associated with long-COVID and immune activation via NFKB pathway, suggesting a pivotal role of mucosal damage and microbial translocation in persistence of immune activation and disease progressing during COVID-19. We and others showed that acute human immunodeficiency virus (HIV) infection is associated with a decrease epithelial gut integrity, allowing translocation of microbial products in the blood. Moreover, we have shown that gut damage persists in PLWH even after years of antiviral therapy (ART). Cytomegalovirus (CMV) is known directly foster gut damage and inflammation and linked disease severity in COVID-19. Moreover, it is hypothesized that CMV could impair immune response. Currently, the influence of microbial translocation on inflammation and function of the immune system during acute and long-COVID-19 remains unknown. This project will characterize the immune response induced by microbial products during acute and long COVID-19. We hypothesized that acute and long COVID-19 will be associated with gut damage, microbial translocation, inflammation and immune dysfunction. We hope this project will pave the way toward new strategies to decrease the burden of long-COIVD syndrome.",,-99,McGill University,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2022 +P25659,468875,Understanding a Public Health Measure in People with Diabetes: Assessing COVID-19 Vaccination Uptake,"Although Canadians have a publicly funded health system, crises like the COVID-19 pandemic can widen health inequities. With knowledge of these health inequities, solutions may be put in place to improve the health of Canadians. Reducing the risk of COVID-19 infection is important so public health measures are key, especially COVID-19 vaccination. Some groups of people, such as people with diabetes, are at risk of health inequities, and this may have occurred with COVID-19 vaccination. Over 3.9 million Canadians have diabetes. People with diabetes are ~ 3 times more likely to be hospitalized, need an intensive care unit, or die from COVID-19 compared to people without diabetes. Unfortunately, little is known about how many people with diabetes have received the COVID-19 vaccine compared to those without diabetes, and if any characteristics of people with diabetes (e.g., their age, sex, or what medications they use) are related to receiving the vaccine. This study has two aims: (1) To learn about the rates of COVID-19 vaccination among people with and without diabetes: and (2) To learn if there are any characteristics of people with diabetes that are associated with receiving a COVID-19 vaccine. We will link several large databases within Alberta to assess the rates of COVID-19 vaccination among people with and without diabetes. Then, we will describe the characteristics of people with diabetes, including children, who have received COVID-19 vaccination. This study is important because it will provide important information on COVID-19 vaccination rates in people with diabetes, and characteristics of people that have lower or higher vaccination rates. We are working closely with key organizations (This is Our Shot, 19 to Zero, the Vaccine Hesitancy Guide, and Diabetes Canada) so that the information we learn is shared with people with diabetes, the public, health care professionals, and government representatives to keep people with diabetes healthy and safe.",,-99,University of Calgary,65080.58,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2022 +P25661,494270,Long COVID in Bangladesh: Developing Strategies for Identifying and Managing Post-COVID Syndrome in LMIC and Low Resource Health Systems,"Post-COVID-19 syndrome (PCS), or 'long COVID', occurs when individuals experience lingering health complications or illnesses long after the infection is over. PCS is a relatively new health issue, with cases currently identified using definitions that consider the signs and symptoms typically reported by COVID-19-recovered individuals. Current research on PCS, including PCS definitions, has come from high-income countries (HICs). However, due to differences in socioeconomic conditions and disease profiles, what we know about PCS in HICs is not fully applicable to low and middle-income countries (LMICs). This research will study and understand PCS in a LMIC: Bangladesh. We will identify the long-term symptoms and health complications in COVID-19-recovered patients in Bangladesh, and study how other health conditions and socioeconomic factors such as occupation affect whether PCS occurs and how long it lasts. We will examine health as well as economic impacts such as livelihood disruption in individuals who have PCS. Our study will include all COVID-19-tested (COVID-19 positive and negative) individuals in a sub-district of Bangladesh, identified through a globally recognized demographic and health surveillance system. For these individuals, we will identify those with symptoms of PCS and establish a disease profile of the study population. We will then follow all individuals, both with and without PCS, to understand how PCS complications change over time and whether people without PCS later develop it. Advanced statistical techniques will be used to estimate how common PCS is, and determine how PCS appears (e.g., common symptoms), how severe it is, and how long it lasts for individuals who have it. The results will help with the early management of PCS in LMICs and reduce long term impact of the pandemic. It will establish Canadian research partnerships for improved global health emergency response and build Canadian expertise in preparedness and response research.",,-99,N/A,73558.84,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,,Unspecified,,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Economic impacts,2023 +P25662,475357,The SARS-CoV-2 M protein broadly inhibits host protein trafficking and secretion through the host cell secretory pathway,"Coronavirus (CoV) spillover events have caused three recent outbreaks, including the COVID-19 pandemic. In addition to these highly pathogenic CoVs, there are four seasonal 'common cold' CoVs that circulate in humans. It is not well understood how differences between CoVs contribute to pathogenesis and the complexities of what made SARS-CoV-2 a highly transmissible and pathogenic virus compared to previously identified CoVs. Non-structural and accessory proteins of CoVs have been investigated for disruption of host-cell signalling pathways, while CoV structural proteins such as Membrane (M) have been overlooked for similar host interactions. M is the most abundant viral glycoprotein in the virus envelope, and it coordinates the other CoV structural proteins at the ER-Golgi intermediate compartment (ERGIC) for assembly. The ERGIC is an organelle that facilitates bidirectional transport of cargo between the ER and Golgi, and it is rarely repurposed as a site of virus assembly; only CoVs and arenaviruses assemble at the ERGIC. The ERGIC serves as a critical player in secretion and trafficking of host proteins through the secretory pathway. We have discovered three host response pathways that are inhibited by SARS-CoV-2 M, all of which traffic through the secretory pathway. These host proteins are STING (IFN response), ATF6 (ER unfolded protein response) and SREBP2 (cholesterol biosynthesis). Our current objectives aim to determine how M inhibits the secretory pathway and characterize the consequences of interference with these secretory pathway-dependent signaling pathways for both the host cell and SARS-CoV-2. Findings from this research have the potential to identify new roles for the SARS-CoV-2 M protein in repurposing the host secretory pathway and interfering with a variety of host cell processes, revealing how these processes could be exploited to elicit antiviral effects during SARS-CoV-2 replication.",,-99,Dalhousie University (Nova Scotia),77083.46,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P25665,472002,Are changes in skeletal muscle mitochondrial respiratory capacity responsible for lactate release and loss of vascular regulation in sepsis and COVID-19?,"Lactate is an important energy source which is utilized by muscle, heart, and brain tissue. Blood lactate is frequently elevated in patients with sepsis or septic shock, where high lactate is predictive for mortality. In patients with COVID-19, however, even severe pneumonia is typically associated with only a small increase in lactate, and in these patients circulating lactate dehydrogenase (LDH; enzyme responsible for converting lactate to pyruvate) is elevated to the extent that it is related to disease severity and even mortality. These observations have led to the hypothesis that the muscle's ability to produce energy is impaired in sepsis but may be normal or even exaggerated in COVID-19. The results of this work may significantly change our perception of cardiovascular regulation in critically ill patients with sepsis and COVID-19 and may guide future therapies or prevent potentially harmful interventions; for example, excessive fluid administration with the purpose of normalizing lactate. The muscle's ability to utilize lactate and an explanation for the high LDH levels are not well described in COVID-19; therefore, by use of state-of-the-art research techniques, this study will explain where lactate is being taken up (muscle, heart, or lungs). This translational work may help explain the muscle fatigue experienced by COVID-19 and septic patients after critical illness. This study will utilize a high-quality research design with gold-standard measurement techniques in specific patients of interest with direct relevance to Canadian public health and treatment strategies for sepsis and COVID-19. As sepsis-induced multiple organ failure is a major cause of mortality and morbidity in critically ill patients, this study is necessary and of high importance. In view of the recent COVID-19 pandemic, the overwhelming strain on intensive care units worldwide places high priority for experimental studies that will optimize efficiency of critical care patient treatment.",,-99,University of Copenhagen (Denmark),109655.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Europe,Unspecified,,,,Denmark,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2022 +P25668,424876,"What are the impacts of the COVID-19 pandemic on the mental health of children aged 5-12, and what are the particular issues for children with disabilities or chronic illnesses? A scoping review of the issues experienced and promising avenues for intervention.","COVID-19 has impacted the daily lives of everyone, including primary school-aged children aged 5 to 12 who may be experiencing stress and anxiety. Some children may be at higher risk of mental health problems, including those with disabilities or chronic conditions. We know that these children may be at higher risk of mental health problems than their peers, and confinement, reduced in-person services, and changes in routine can have a significant impact on them. This study will synthesize what is known about the impacts of the COVID-19 pandemic on all children aged 5 to 12, highlighting the particular impacts on students with disabilities or chronic conditions. The study will also explore risk and protective factors for children's mental health, as well as promising avenues for intervention to promote better mental health in these young people. The question that will guide the knowledge synthesis will be the following: What are the impacts of the pandemic on the mental health of children aged 5-12, and what are the specific issues for children with disabilities or chronic illnesses? Relevant information will be extracted from scientific literature and various reports. The information will be analyzed with a committee of partners including families and health and social services stakeholders. A consultation will be carried out to anchor the results of the knowledge synthesis in the Quebec context. The study's recommendations will support the mental health of all Canadian children aged 5 to 12 and concrete actions in Quebec related to confinement and the return to school. Particular attention will be paid to children with disabilities or chronic illnesses in order to promote health equity.",,-99,Université de Sherbrooke,35568.67,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25678,495081,"Assessing Zika virus infection during pregnancy and adverse fetal, infant, and child outcomes: The Zika virus (ZIKV) Individual Participant Data (IPD) Meta-analyses (MA) Phase II and the analysis of surveillance-based IPD data. (ZIKV-IPD-MA-2S)","Estimating the short- and especially the long-term- effects of Zika virus (ZIKV) infection during pregnancy is challenging. Potential ZIKV-related adverse outcomes are: congenital malformations (called as well Congenital Zika Syndrome or CZS), pregnancy loss, neonatal and child mortality, and developmental issues. However their assessment is threatened by the absence of, or lack of good quality data, and a series of biases that are not often accounted for when analyzing ZIKV-related data. Zika is a virus mostly transmitted to humans by the bites of infected Aedes mosquitoes, but can be transmitted vertically from pregnant individuals to their fetuses. In 2016, a public health emergency of international concern (PHEIC) was declared due to the increase of microcephaly in children born to ZIKV-infected pregnant individuals. After six years of the PHEIC, ZIKV is still a threat. Over 40,000 cases were reported in 14 countries of the Americas region in 2022 and still, robust estimation of the short- and long-term effects of Zika during pregnancy are lacking. We propose a research project to contribute to the estimation of ZIKV-related risks, using data from 64 estudies (22 countries) participating in the ZIKV- Individual Participant Data (IPD) Consortium. The ZIKV-IPD consortium is an initiative led by the World Health Organization (WHO), created in 2017 to bring together multidisciplinary researchers to conduct a synthesis of the available literature called IPD meta-analyses (IPD-MA), of ZIKV-related cohorts and surveillance-based. Our research includes harmonization of available data to be analyzed while addressing issues related to the heterogeneity of the data (e.g., definitions, study designs, type of measurements, etc), and developing and applying statistical methods to de-bias the data and providing robust epidemiological estimates. We will contribute to informe public policy and decision-making in the healthcare system and among pregnant individuals.",,-99,McGill University,73558.84,Human Populations,Unspecified | Not applicable,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2023 +P25682,468864,Improving flexibility and performance of the Acute Care Enhanced Surveillance (ACES) System for public health surveillance: an ensemble of state-of-the-art machine learning and rule-based natural language processing methods,"The Acute Care Enhanced Surveillance (ACES) system, based at Kingston, Frontenac, Lennox & Addington (KFL&A) Public Health, is a public health surveillance system that monitors patient activity in near-real- time at 97% of Ontario's acute care hospitals. The system groups patients into health conditions (syndromes) based on their chief complaint in the emergency department. Epidemiologists use ACES to identify disease outbreaks or other potential public health problems from patterns in hospital activity. While useful for tracking COVID-19, key weaknesses in how the system groups patients were found. This project proposes to improve the way the system groups patients by using state-of-the-art computational methods (machine learning and natural language processing) that do not rely on one rigid model only, and that can better classify key pieces of information from the chief complaint. Diverse experts in epidemiology, public health, medicine, and computer science will collaborate to determine how best to define new health conditions, based on these classifications and other available patient information. The ACES system will be updated so that it automatically uses and displays these new health condition groupings, which will compliment those that are already there. These new health condition definitions will make ACES more flexible and relevant, providing public health leaders with an effective tool to better detect and monitor public health threats like opioid consumption issues and new diseases like COVID-19.",,-99,"KFL&A Public Health (Kingston, Ontario)",78410.34,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2022 +P25686,451082,COVID-19 and Vaccine Confidence in Black Communities: Status Report and Education and Mobilization Programs,"How can we explain that the COVID-19 pandemic continues to have more devastating consequences for racialized communities when they are the least willing to take preventive measures such as vaccination? To date, this question has no answers because there is a lack of reliable information to inform authorities and public health policy makers in Canada. Our project aims to better understand the factors that explain the distrust of Black communities in Canada towards COVID-19 vaccination. Moreover, it will allow us to understand how these factors evolve and change over time, depending on the evolution of the pandemic and the associated health measures as well as the vaccination promotion campaigns at the heart of this project. Participants in this research will be recruited in Ontario and Quebec, both among the vaccinated and the unvaccinated; these two provinces account for nearly 80% of Black communities in Canada. They will provide information on their profile and whether or not they will be vaccinated, their knowledge, beliefs and attitudes towards COVID-19 vaccines, their experiences of discrimination and their mental health. Focus groups will also be held with vaccinated and unvaccinated participants, Black community leaders and primary health care and public health professionals. The information collected will be analyzed and the results will be used to set up education campaigns on the vaccine. These campaigns will help reduce erroneous or false beliefs about vaccines and increase confidence in the benefits of getting vaccinated against COVID-19. The programs and tools that will have proven themselves through this project can be used in the future in other vaccination contexts with Black communities in Canada and elsewhere in the West.",,-99,University of Ottawa,159175.15,Human Populations,Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P25689,460302,Addressing the Wider Impacts of the COVID-19 Pandemic on Mental Health and Substance Use in Canada,"Mental health challenges affect all Canadians. Yet many Canadians lack access to mental health care services, with equity in access a key concern for specific groups due to gender, ethnicity, socio-economic status, geographic isolation, and immigration status issues. The COVID-19 pandemic is exacerbating mental health challenges and widening service gaps, especially among those in marginalized groups and those with pre-existing mental health issues, making it a critical time to provide tools that will improve mental health at the population level. CAMH has been conducting a cross-sectional survey to monitor changes in mental health and substance use during the pandemic. The initiative builds on our experience to engage Canadians in the process of understanding and acting on mental health and substance use issues caused by the COVID-19 pandemic. We will develop Learning Systems that use machine learning to develop an automated, continuously improving and sustainable infrastructure to track patterns in population mental health over time, and to inform improvements in access to services. Through close engagement with people with lived experiences, this initiative will allow Canadians to lend their voices to improving mental health interventions.",,-99,Centre for Addiction and Mental Health (Toronto),401220.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25697,452778,Deciphering the functional and morphological interplay between flaviviruses and mitochondria,"With no available therapies, infections with flaviviruses constitute a major public health concern worldwide. While dengue virus (DENV) causes the most prevalent arthropod-borne viral disease and may be fatal, Zika virus (ZIKV) infection in utero can lead to severe neurodevelopmental defects in newborns, including congenital microcephaly. In Canada, West Nile virus (WNV) is endemic and causes severe encephalitis and eventually death. Thus there is an urgent need to better understand flavivirus pathogenesis at the molecular level in order to identify novel antiviral targets. In order to generate an intracellular environment favorable to viral replication, flaviviruses induce the morphogenesis of organelle-like replication factories (vRF) via poorly understood mechanisms. These vRFs host viral RNA replication and regulate several processes important for viral pathogenesis. We have previously reported that vRFs make contacts with mitochondria, which in turn exhibit an elongated morphology. This correlates with drastic perturbations in their composition, metabolic activity and contribution to critical antiviral processes such as innate immunity and apoptosis. However, the molecular mechanisms governing this flavivirus-mediated mitochondrial reprogramming and how this impact on viral replication remain mostly enigmatic. In this project, we propose to dissect at the molecular and ultrastructural levels the interplay between mitochondria and several flaviviruses of clinical importance such as DENV, ZIKV and WNV. Ultimately, this project might unveil novel therapeutic targets.",,-99,"INRS - (Québec, QC)",551991.82,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P25698,479263,Studying Zika virus neuropathogenesis and its determinants in vivo using a newly engineered zebrafish infection model,"Infections with Zika virus (ZIKV) constitute a major global public health concern worldwide. Indeed, the recent ZIKV outbreak in the Americas revealed that infection of pregnant women can lead to congenital transmission, infection within the fetal developing brain and eventually to microcephaly in the infant. Most importantly, no antiviral therapies or vaccine against ZIKV are currently available, as we poorly understand how the disease develops. Addressing these questions is challenging since it requires the use of animal models (such as mice) which are limited in terms of genetic manipulation, access to infected regions of the developing brain and number of handled individuals. In that respect, the zebrafish model has emerged as a very powerful animal model to study vertebrate brain development in vivo. Indeed, Zebrafish are small fish which develop very fast and have a transparent body. This means that brain cells can be easily visualized and that it is possible to observe the impacts of genetic manipulations and infections. Most importantly, ZIKV symptoms and developmental defects in humans can be replicated in zebrafish larvae. Relying on our wide expertise in virology and neurodevelopment, this proposal aims at better understanding ZIKV neuropathogenesis in vivo by taking advantage of this novel infection animal model based on zebrafish developed by our laboratory. We will characterize the nervous cell populations impacted by ZIKV infection and study the viral determinants required for neurovirulence. Our model may emerge as an easy-to-handle and flexible tool to study the host determinants of ZIKV neuropathogenesis and to quickly screen antiviral drug candidates in vivo.",,-99,"INRS - (Québec, QC)",745375.46,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P25701,468301,"Impact of aerosol box use during cardiopulmonary arrest: A multicenter, randomized trial","Many patients diagnosed with Coronavirus Disease 2019, or COVID-19, suffer from severe illness requiring intensive medical care. Patients suffering from cardiac arrest require aerosol-generating medical procedures (AGMPs) that spread virus throughout the air. When healthcare providers perform these procedures, they are at risk of becoming infected with COVID-19. During the pandemic, a new device called an aerosol box was invented to protect healthcare providers while they perform AGMPs. This device is placed over top of the patient's head while they are lying on a stretcher, shielding the doctor's face from viruses in the air. Unfortunately, there is limited published research describing how well the aerosol box works to protect healthcare providers, and whether or not use of the box impacts patient care. Our study will use a plastic manikin head and chest as a patient. Teams of physicians, nurses and respiratory therapists will work together to care for this simulated patient. We will use a special fluorescent powder to mimic COVID-19 particles. When the teams perform their tasks, the powder will be spread throughout the air, just like viral particles would in a real setting. We will then use a particle counter to detect particles in the air, and a camera and UV light to detect where the powder has spread on surfaces. Half of the teams will use the aerosol box, and the other half will not, which will allow us to determine if it is effective at preventing spread. By seeing where the powder has spread, we will also determine how risky it is for healthcare providers to care for patients in cardiac arrest. Concomitantly, we will measure how long it takes for providers to complete important tasks required to save the patient. This is important because it will help hospitals decide if aerosol boxes should be routinely used when caring for COVID-19 patients. Our study will also help hospitals develop rules to reduce healthcare provider risk during the COVID-19 pandemic.",,-99,University of Calgary,366541.24,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Infection prevention and control,"Supportive care, processes of care and management | Clinical trials for disease management | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2022 +P25706,445729,Les répercussions sur la santé de la perte d'un proche en temps de pandémie: trajectoires de deuil et répercussions sur la santé biopsychosociospirituelle des circonstances du décès et des restrictions à l'accompagnement des mourants et aux rituels funéraires,"Covid-19 has led to unprecedented socio-health measures in several countries which have had effects on the quality of life and health that we are only beginning to see. In particular, the ban and then the drastic restriction of visits for people who are dying or in palliative and end-of-life care and farewell rituals for the deceased (funeral toilets prohibited, the coffin cannot be displayed open, the number reduced of participants in ceremonies, etc.) have changed the grieving process for many people, whatever the causes of death. However, there have never been as many deaths in Canada as in 2020, during which approximately 300,000 Canadians are estimated to have died. If we think that, for every deceased person, 5 to 9 people are bereaved, millions of people are affected in Canada. This raises fears that grief that began during the current pandemic could become a significant public health problem in the coming months and years. Indeed, the circumstances of these deaths and the rituals can constitute significant risk factors for the health of the bereaved. The project submitted here aims to identify, through an online survey and semi-structured interviews, the factors that may have helped or harmed the trajectories of grief and the health of the bereaved in general. The identification of these factors, their evolution over a long time (two years) and the analysis of their relationships with health will make it possible to document the grieving processes, what disrupts and facilitates them, particularly in terms of support. loved ones at the end of life, monitoring of the bereaved after death and health rules for funeral rituals. This evidence will make it possible to improve healthcare practices and public health policies.",,-99,Université du Québec à Chicoutimi,151937.57,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25707,429444,Computer-aided discovery of synergistic drug combinations with Remdevisir for COVID-19 through mechanism-based drug repurposing and combinatorial organoid screening.,"With more than 4 million cases and over 300,000 deaths worldwide, it is critical to find an effective treatment against COVID-19 and to find it fast. Hopes for ending the pandemic largely rely on new vaccines, however the development of vaccines typically takes years and even if one is available today (which is not), its approval will take more than a year in the most optimistic scenario. Thus, the only realistic option for rapid COVID-19 treatment is drug repurposing. Drug reprofiling (repurposing) implies the use of existing drugs approved for other indications, and yet showing useful activity against SAR-CoV-2 virus. One well-known example of this strategy is remdesivir, currently the most promising treatment against COVID-19, and which was originally developed as Hepatitis C drug. Although very promising, remdesivir is still modestly efficient against COVID-19 and hence, if one could further boost its effectiveness by using it in a synergetic combination with another reprofiled drug, the pandemic might finally see the resolution. This consortium of national and international scientists wants to identify such much-needed SARS-CoV-2 inhibitor among known drugs, which then will be used either as stand-alone therapy for COVID-19 or a synergetic 'booster' for remdesivir. This team of scientists was recently awarded four COVID-19 rapid response grants to build a state-of-the-art organoid-based screening platforms established at UBC CL3 infectious disease facility, working in sync with high-resolution crystallography and artificial intelligence-enhanced molecular modeling and imaging platforms. We are ready and prepared to push forward this project even in this extremely condensed 1-year timeframe. The proposed research will generate high quality data on COVID-19 treatments shared through extensive international collaborations, will initiate critical clinical trials, and will position Canada as a world leader in the global fight against the pandemic.",,-99,University of British Columbia,1500371.7,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P25708,443064,COVID-19 Variant Network - Computer-aided discovery of synergistic drug combinations with Remdevisir for COVID-19 through mechanism-based drug repurposing and combinatorial organoid screening.,"With more than 4 million cases and over 300,000 deaths worldwide, it is critical to find an effective treatment against COVID-19 and to find it fast. Hopes for ending the pandemic largely rely on new vaccines, however the development of vaccines typically takes years and even if one is available today (which is not), its approval will take more than a year in the most optimistic scenario. Thus, the only realistic option for rapid COVID-19 treatment is drug repurposing. Drug reprofiling (repurposing) implies the use of existing drugs approved for other indications, and yet showing useful activity against SAR-CoV-2 virus. One well-known example of this strategy is remdesivir, currently the most promising treatment against COVID-19, and which was originally developed as Hepatitis C drug. Although very promising, remdesivir is still modestly efficient against COVID-19 and hence, if one could further boost its effectiveness by using it in a synergetic combination with another reprofiled drug, the pandemic might finally see the resolution. This consortium of national and international scientists wants to identify such much-needed SARS-CoV-2 inhibitor among known drugs, which then will be used either as stand-alone therapy for COVID-19 or a synergetic 'booster' for remdesivir. This team of scientists was recently awarded four COVID-19 rapid response grants to build a state-of-the-art organoid-based screening platforms established at UBC CL3 infectious disease facility, working in sync with high-resolution crystallography and artificial intelligence-enhanced molecular modeling and imaging platforms. We are ready and prepared to push forward this project even in this extremely condensed 1-year timeframe. The proposed research will generate high quality data on COVID-19 treatments shared through extensive international collaborations, will initiate critical clinical trials, and will position Canada as a world leader in the global fight against the pandemic.",,-99,University of British Columbia,70553.29,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2021 +P25709,448867,The RECLAIM (REcovering from COVID-19 Lingering symptoms Adaptive Integrative Medicine) trial,"We propose to develop a Canada-wide, open-label, pragmatic, adaptive randomized clinical trial platform to assess the effectiveness of various interventions in patients with lingering symptoms of COVID-19 (""long COVID""). After a run-in period, participants will be randomized using an adaptive randomization scheme (that favors more promising therapies and discontinues ineffective ones, allowing new interventions to be introduced and tested) to receive either standard of care (control) or the study intervention. This trial will have 4 arms. An Interdisciplinary Science Committee will determine and prioritize interventions to be tested. The top three choices will be used in our four arm study, with the fourth arm being standard of care for symptomatic treatment. Potential interventions include immunomodulatory therapies (e.g. pegylated alpha-interferon), antivirals, monoclonal antibodies, anti-inflammatory (e.g. colchicine), anti-platelet agents (e.g. aspirin), fluvoxamine, and traditional Chinese medicine, among others. Interventions will last for 4 weeks and participants will be followed for 12 weeks. Approximately 800-1000 patients with ""long COVID"" will be recruited across Canada. Inclusion criteria include patients age>16, with confirmed COVID-19 and lingering symptoms that have lasted over 3 months. A concerted effort will be made to recruit a study population that is diverse in terms of age, sex, gender, race, ethnicity and comorbid conditions. Primary outcome: the validated Post-COVID-19 Functional Status scale (PCFS). Secondary outcomes: symptom checklists, De Paul Symptom Questionnaire 2, health-related quality of life (SF-36), 6 minute walk test, and re-integration to normal living. Results from this trial will accelerate the availability of high-quality, real-time evidence and solutions to enable Canada to improve the clinical care of patients with ""long COVID"".",,-99,University Health Network (Toronto),794444.82,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Post acute and long term health consequences | Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase),2021 +P25710,474666,Long COVID Web: Pan-Canadian Post-COVID Condition Research Network,"COVID-19 has touched every corner of the world. As reported by the World Health Organization, more than 634 million people have been infected by the virus. For most people who are infected, symptoms of COVID-19 are short-lived but for some, symptoms remain long after infection is over. Known as post COVID-19 condition, or long COVID, more than 150 million people worldwide live with long COVID, including roughly 1.4 million Canadians. The wide range of symptoms can include general symptoms such as tiredness; breathing and heart symptoms such as cough and chest pain; digestive problems; severe joint and muscle pain; or brain-related symptoms such as difficulty thinking or sleeping, headaches, depression or anxiety. Any of these symptoms can affect the daily lives of people with long COVID. Without proper diagnosis and management, the effect on Canada's healthcare, financial and societal systems is profound. Likewise, some communities have been affected more than others. The negative impact on the health and social well-being of individuals, families and communities is significant and must be addressed immediately. Founded upon the unique perspectives and knowledge of patients, Indigenous communities and researchers, Long COVID Web will create a Canada-wide research network that will i) unravel the complicated web of long COVID disease biology and behavior; ii) develop accurate diagnostic tools, treatments and rehabilitation; and iii) understand and widely share how care and societal systems must adjust to improve the healthcare experience and also ensure socio-economic safety for all. Over the next five years, Canada's leading experts and voices in long COVID will develop standardized clinical practices and treatments across the spectrum of disease. The Network findings will help influence healthcare and societal policies that will ensure the well-being and livelihood of those living with long COVID in Canada and across the world.",,-99,University Health Network (Toronto),14682279.53,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health service delivery,2022 +P25711,475681,Investigating the Impact of Tumor Necrosis Factor Inhibitors on SARS-CoV-2 mRNA Vaccine-induced Immunity in Immunocompromised Patients with Immune-mediated Inflammatory Diseases,"Immunocompromised patients are at increased risk of viral infections and adverse outcomes following infection, including intensive care unit admission and in-hospital mortality. Further, they run the risk of shedding virus for longer, leading to increased risk of transmission or the generation of immune escape variants. While vaccination reduces the risk of infection in immunocompromised patients, it may be less effective in patients treated with immunomodulatory or immunosuppressive therapies. In this study, we will focus on immunocompromised adult patients with inflammatory bowel disease (IBD). Patients with IBD are often treated with drugs that block an inflammatory molecule called tumor necrosis factor (TNF). Treatment with TNF blocking agents is known to impair antibody responses to vaccines developed for seasonal influenza and SARS-CoV-2. In this proposal, we will conduct an in-depth investigation of the immune cells (T and B cells) in these treated IBD patients to further understand the detailed mechanism driving the defect in antibody responses to SARS-CoV-2 mRNA vaccination and how we can counteract the defect. Our studies will fill a critical gap in understanding how immunosuppressive treatments, such as TNF blockers, affect the immune response of immunocompromised patients to SARS-CoV-2 vaccination, with broader implications to other viral vaccines. Importantly, we hope to inform public policy on the optimal vaccine development and regimens for the immunocompromised.",,-99,University of Toronto,77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Vaccines research, development and implementation","Supportive care, processes of care and management | Characterisation of vaccine-induced immunity",2022 +P25715,449773,Exploring low-income family caregivers' experiences of accessing health care services for children with inborn errors of metabolism,"Inborn errors of metabolism (IEMs) are a diverse group of genetic diseases that commonly require frequent visits to medical professionals and may be life-threatening. These diseases have been shown to impact the physical, emotional, social, and financial wellbeing of family caregivers. Families with lower monthly income can experience more challenges. This research aims to explore the experiences of low-income family caregivers of accessing care for their children with IEMs that require emergency treatment in Manitoba. Information will first be collected by mailing an invitation to complete an online survey to approximately 200 families. Next, approximately 15 people will be selected to participate in interviews over the phone or videoconference about their experiences accessing care for their children with IEMs. This study will explore barriers to accessing care and whether there are differences in experience depending on how far away families live from Winnipeg. The impact of COVID-19 on these families' experiences accessing care will also be explored, as research has suggested that low-income families have been further impacted by the pandemic with an increased risk of having bad experiences, such as challenges to accessing healthcare. This is the first study to investigate the experiences of low-income family caregivers accessing metabolic care for their children in Manitoba. This research aims to promote health equity in Manitoba and beyond by creating a space for low-income family caregivers to share their stories about accessing care for children with IEMs.",,-99,University of Manitoba,13459.8,Human Populations,Unspecified,Unspecified,Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P25718,432503,"Bien-être psychologique du personnel de l'entretien ménager des hôpitaux canadiens, facteurs déterminants et conditions d'influence en temps de pandémie (COVID-19).","Le personnel de l'entretien ménager dans les hôpitaux est en première ligne pour lutter contre la COVID-19 mais on en parle trop peu. Ces personnes s'exposent, se mettent à risque et travaillent sans relâche pour assurer la sécurité de tous les patients mais aussi de tout le personnel de l'hôpital. Ils portent une lourde responsabilité et vivent un stress psychologique élevé. Notre équipe de chercheurs veut mesurer la détresse psychologique des travailleurs de l'entretien ménager pendant la COVID-19 mais aussi recueillir des informations sur ce qui favorise cette détresse (facteurs personnels, organisationnels, ou autres). Nous allons donc interroger par sondage électronique des travailleurs de l'entretien ménager dans plusieurs hôpitaux canadiens, et nous rencontrerons des groupes de travailleurs pour discuter avec eux pour bien comprendre leurs préoccupations.En plus nous conduirons des entrevues avec des personnes clés tels que des gestionnaires, ou des représentants des syndicats pour discuter des stratégies à mettre en place au niveau des établissements pour prévenir la survenue de ce stress psychologique. Mieux comprendre ce qui détermine la détresse psychologique des travailleurs de l'entretien ménager permettra d'informer les établissements de santé à mieux prévenir cette détresse en modifiant leurs processus. Avec des outils simples pour identifier cette détresse, les établissements de santé pourront aussi surveiller périodiquement la santé psychologique de leur personnel à l'entretien ménager et lui offrir les services appropriés en tout temps, même à distance de la COVID-19.",,-99,University of Ottawa,145691.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P25719,480678,Clonal Hematopoiesis and Critical Illness,"Clonal hematopoiesis (CH) is a condition in which somatic mutations in a single blood stem cell lineage lead to the overproduction of mature blood cell 'clones'. It is well-established that CH increases in prevalence with age and confers substantially greater risks of blood cancer and mortality. A relationship has been uncovered between CH and altered inflammatory immune function, which suggests that it may play a role in the development or progression of other non-cancerous, non-blood-related diseases. There is a considerable amount of evidence showing that several common CH mutations increase the risk of cardiovascular disease, for example. Although CH has not been well-studied in relation to critical illness, there are striking similarities between these two disease categories. Prevalent infections such as COVID-19 and C. difficile also tend to be more severe in older individuals and have similarly been associated with excessive inflammation and genetic influences. Recent evidence suggests that these and other critical illnesses are more severe among patients with existing CH; however, there is a need to replicate these results on larger and more diverse scales. This research will use targeted next-generation sequencing and whole-genome analysis to identify CH mutations associated with critical illness. These findings will then be used to inform investigation of cellular and molecular interactions occurring when both conditions are present, which may increase the severity of infection experienced by the patient. In an age when mortality rates from COVID-19 are continuously growing, this research holds the potential to significantly improve the prevention, management and outcomes of critical illness in the Intensive Care Unit setting.",,-99,"Queen's University (Kingston, Ontario)",13724.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Prognostic factors for disease severity,2021 +P25721,449380,A Randomized Controlled Trial to Test the Efficacy of The CONNECT Program: A Telephone-Based Mental Health Program for Socially Isolated Older Adults,"Intent: As we see the population of adults aged 65+ increase in Canada, we need to develop new ways to respond to the challenges this population faces. Older adults often report feeling socially isolated, lonely, and report mental health problems such as anxiety and depression. These feelings are common during the COVID-19 pandemic. This research will test to see if a telephone based mental health program can help people manage these feelings. The project: The telephone program that is being tested in this research allows older adults to connect with others through weekly group calls. The people who participate in this research will be assigned to either the treatment condition (the 6-week telephone program), or the waitlist condition (they will not participate in this program at this time). The treatment group will complete activities and learn strategies that will help them learn about their emotions and ways to manage these feelings in the future. Methods: These telephone group calls will consist of learning new skills (e.g., mindfulness) to help manage emotions, along with group discussions. People in both groups will complete questionnaires before and after the program. These questionnaires will help us see how people's experiences change throughout this program, and how people in the treatment group differ from people in the waitlist group. We expect to see people in the treatment group experience lower levels of social isolation, loneliness and mental health symptoms at the end of the program. Significance and relevance: This research project will show that this program helps older adults manage feelings of social isolation, loneliness and symptoms of depression and anxiety. Looking forward, this program can be offered to older adults across Canada.",,-99,University of Manitoba,13459.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25733,449608,Mapping conspiracy beliefs and psychological distress during the COVID-19 pandemic in Canada,"The COVID-19 pandemic and the health guidelines aimed at limiting its transmission are affecting the mental health and well-being of Canadians. Evolving scientific knowledge and frequent adjustments to public health recommendations are contributing to the climate of uncertainty and loss of individual control that fosters the spread of misinformation and erroneous beliefs about the disease. The overall objective of the project will be to clarify the complex interrelationship between conspiracy beliefs and psychological distress, and to identify their underlying social determinants. The project is part of the pan-Canadian COHESION study, conducted on 10,000 individuals and families, which collects real-time data, via a downloadable mobile application, on anxiety-depressive symptoms, social interactions, mobility, activity spaces, living conditions and attitudes regarding the COVID-19 pandemic in order to understand how it affects health and social inequalities in health. An initial questionnaire and monthly follow-up questionnaires will make it possible to describe the spatiotemporal variations in indicators of psychological distress and erroneous beliefs related to the pandemic, and to analyze the effect of distal causes (e.g., social capital, neighborhood social environment) on their interrelation. The identification of social determinants and a common mapping of mental health and conspiracy beliefs could guide the current and future efforts of public health authorities in their outreach work with communities more reluctant to follow health instructions, especially as a mass vaccination campaign against COVID-19 approaches.",,-99,Université de Montréal,13459.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25736,464063,COVID-19 in working age Canadian adults: Long-term follow up of infections and immune responses,"COVID-19 infections continue to impact our lives and economy despite vaccinations and other protective practices. Many of the infections are caused by variants to the original virus. Due to the ability of this virus to mutate and our inability to control it world-wide, it is likely to continue to plague humans for many years to come. This study is a 2-year follow-up of adults who are currently participating in two ongoing cohort studies. These health care and education workers are on the front lines due to their work, putting themselves and their household members at risk for contracting this potentially deadly disease. We will follow these participants to determine the incidence of COVID-19 and the pattern of antibody responses in people who are/are not vaccinated and were/were not previously infected. We will also monitor the response to and impact of booster vaccines, if and when they become available.",,-99,Sinai Health System (Toronto),676050.03,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +P25737,486638,Qualitatively Evaluating Virtual Care Use in Long-Term Care during the COVID-19 Pandemic,"During the COVID-19 pandemic, long-term care (LTC) homes had to make the shift to primarily offering virtual physician care to ensure the health of residents. This shift led to challenges such as supporting consistent cellular and Wi-Fi connection and supporting residents with high care needs by using virtual care. To look further into these challenges, my research will explore how LTC residents and staff in British Columbia's Fraser Health region experienced the effectiveness and equity of virtual care during the pandemic. My research will contribute to two CIHR Catalyst studies that seek to evaluate virtual care use in LTC during the COVID-19 pandemic from the perspectives of different user groups. The key findings from these groups will then be used to support and tailor virtual health so that it be used in a way that is able to support continuing use in the future in LTC homes. For my thesis research, I will identify appropriate virtual care domains to guide interview questions asked to physicians, family care partners, LTC residents and staff and then conduct one-on-one interviews. I will then take the results from both CIHR studies and triangulate them to find constant themes found in both so as to identify key take-away messages. My research will be used to directly support enhancing the effectiveness and equity of virtual care in LTC in the Fraser Health region and beyond. This research is important because virtual care was already on the rise in LTC homes and is expected to increase in the future.",,-99,"Simon Fraser University (Burnaby, B.C.)",13021.09,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Health Systems Research,Health service delivery,2022 +P25739,454634,Addressing the shortage of professional resources within CLOSMs: strengthening recruitment and retention strategies for the benefit of New Brunswick's Francophone and Acadian communities,"Across the country and elsewhere, COVID-19 has highlighted the human resource gaps already well-felt in health systems. The provision of health care and services in New Brunswick is weakened by a shortage of registered nurses and physicians, which particularly affects rural areas, where official language minority communities (OLMCs) are concentrated. Since 2008, the Vitalité Health Network (Network), whose operating language is French, has served OLMCs spread across four geographic zones. However, there are approximately 100 physician positions and approximately 200 registered nurse positions to be filled in the territory administered by the Network. Given this reality, combined with the current health crisis, it is imperative to strengthen the Network's recruitment and retention strategies to ensure its viability and maintain health care and services that meet the needs of OLMCs. In a spirit of co-creation of knowledge, we have therefore established a partnership with the Network. The results of this study will allow our partner to identify and implement concrete solutions that come from its context in order to increase the recruitment rate and promote the retention of professionals in their positions. By taking stock of vacant positions and examining the turnover rate, it will be possible, on the one hand, to determine whether the most significant challenges are in terms of recruitment or retention. On the other hand, it will be a question of examining the factors that make the internal environments attractive, such as working conditions, and external (or community) environments, such as the living environment of professionals. The methodology is based on a mixed design that combines quantitative and qualitative approaches.",,-99,Université de Moncton (New Brunswick),76889.16,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Health workforce,2021 +P25740,451256,COVID-19 Vaccine Confidence Among At-Risk and Under-Vaccinated Groups Within HIV and Rheumatic diseases (CONFIDENCE),"People living with human immunodeficiency virus (PL-HIV) as well as people living with systemic autoimmune rheumatic diseases (PL-SARDs) are more likely to have severe COVID-19 and to die of it compared to individuals in the general population. Vaccination against COVID-19 is key to reducing these risks. However, ~20% of the eligible Canadian population is not yet vaccinated. Moreover, recent data suggest that vaccine rates and acceptance are lower in migrants, women, and people with physical disabilities. These 'especially vulnerable subgroups' are frequent among PL-HIV and PL-SARDs. Previous literature reported that vulnerable subgroups of PL-HIV and PL-SARDs share common reasons that lead to reduced COVID-19 vaccine uptake. We propose to work along with members of these subgroups to uncover those reasons and to empower trusted members of these communities so they can communicate with their peers in ways that motivate behavior change (i.e., vaccine acceptance). In order to understand the reasons that could enhance COVID-19 vaccine confidence in the aforementioned vulnerable groups, we will conduct virtual group meetings (i.e., focus groups) and individual phone interviews with those not willing to join the group discussions. The information gathered from these activities will then be used to design a training program for community members to promote vaccine confidence through motivational interviewing and storytelling techniques. The feasibility of training community members in motivational interviewing and an initial feedback on the impact of the intervention promoting behavioral change in their communities will be evaluated. Our team, composed of community members, health care providers and researchers, has the required expertise to accomplish the work proposed in a timely fashion, to disseminate the study results and to advocate for implementation measures to address other aspects to promote vaccine acceptance identified during the course of the study.",,-99,Research Institute of the McGill University Health Centre,158379.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P25741,442399,COVID-19: Implementation of virtual P.I.E.C.E.S™ for resident care planning with family to build and sustain team collaboration and resilience for the workforce in LTC,"COVID-19 restrictions resulted in profound isolation for older adult residents in long term care (LTC) homes, which exacerbated their physical, social, and mental health care needs (Chu et al., 2020). Illness due to COVID, in combination with LTC workplace challenges, also led to losses of staff and greatly impacted the mental and physical health of the remaining workforce, compounding the detrimental effects on residents (Shechtera et al. 2020). The primary goal of the proposed research is to improve pandemic preparedness, provide a workforce strategy for integrated resident care and safely engage family in care partnerships, to avoid the recurrence of the detrimental effects of the first pandemic wave. A secondary goal is to provide evidence for practices and policy and build research capacity that can be implemented in LTC homes. Facing the likelihood of future COVID-19 outbreaks coinciding with flu season, LTC homes, residents, their families, and staff need a clear strategy in place to better manage resident care. A plan that involves family members, promotes communication, and supports the resilience of Registered Practical Nurses (RPNs), the largest front-line regulated workforce, and staff so they can practice safely and effectively during a pandemic. This project, situated in two partner LTC homes, will investigate a novel virtual intervention of P.I.E.C.E.S.™ (PIECES) for team-based planning of resident care.",,-99,University of Western Ontario,114097.03,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Infection prevention and control,,2020 +P25746,448819,What impacts COVID-19 vaccine uptake in Métis Citizens in Ontario? A population-based data linkage study.,"Individual decisions about vaccination are affected by many factors including previous experiences with vaccination, risk/benefit assessments of vaccination and the ease of access to vaccination among the general population. Broader factors also impact this decision among Indigenous peoples, including historic, institutional and political factors, yet little is known about factors affecting vaccination decisions among Métis. Accounting for one third of Indigenous people in Canada, the Métis are a distinct Indigenous identity with its own language and cultural traditions, alongside varied experiences with systemic racism and oppression as being neither accepted as White or First Nations. With COVID-19 vaccines rolling out across Canada and vaccine hesitancy high in minority populations including Métis, it is important to understand factors affecting COVID-19 vaccine uptake for Métis and support optimal uptake. The Métis have been referred to as ""hidden"" Indigenous peoples reflecting not only the history of the Métis but the lack of Métis-specific health research. It is particularly important to explore reasons for vaccinating or not among Métis as they have been shown to have higher rates of underlying medical conditions that increase the risk of severe illness from COVID-19, including COPD, asthma, congestive heart failure and diabetes, than the non-Indigenous population. This study will identify factors that impact COVID-19 vaccine uptake in Métis Citizens in Ontario. We will link a population-based survey led by the Métis Nation of Ontario that collected information on the psychological barriers to vaccination behaviour among Ontario Métis using a standard scale, to administrative data on uptake of COVID-19 vaccines in Ontario (COVax Ontario dataset). This research, along with consultations with MNO citizens, may inform efforts needed to ensure optimal uptake of COVID-19 vaccines in the Métis and support equitable access to the vaccines in Ontario.",,-99,University of Waterloo (Ontario),144557.18,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +P25749,447504,Molecular determinants of Zika virus propagation and pathogenesis in human glial cells,"All viruses require a host cell in which to grow and spread. Thus, all viruses make use of cellular processes, and these processes dictate whether a virus can successfully grow in any given cell. Arboviruses are viruses spread by arthropods, such as mosquitos. Zika virus (ZIKV) is a newly re-emerging arbovirus that has been identified as a public health threat by the World Health Organization. The mosquito that transmits ZIKV has been found in Canada, and climate change will make the mosquito and virus more prevalent. ZIKV causes birth defects and can have long-term effects in those children who survive infection. The severity of disease depends upon the age of the developing child, with most severe manifestations occurring during the first trimester of pregnancy, indicating age-related factors in ZIKV growth and pathology. Our prior global protein screens identified panels of cellular proteins that are common in ZIKV-susceptible cells, and others that are common in cells in which the virus cannot grow. We now seek to understand how a small number of these identified cellular genes and proteins cause their effects, and also at what stage during cell development these proteins switch from allowing ZIKV growth to inhibiting ZIKV growth.",,-99,University of Manitoba,79444.48,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P25750,476122,Blood Based Biomarkers of Neurodegeneration Across the Health Spectrum,"Blood tests are currently used to diagnose a variety of diseases, this is done by measuring molecules in the blood that have been produced or affected by the disease, causing the levels to vary from healthy people. Despite this being a standard practice for a variety of diseases, we have lacked the ability to perform tests like this for brain diseases. Instead, we have relied on diagnosing conditions like dementia with memory tests, that are not very accurate, and brain imaging, which is expensive and not accessible for everyone. However, we are finally able to measure proteins in blood that have come from the brain using newly available technology. This enables the development of blood tests for brain diseases that affect these proteins. The goal of this study is to understand what these protein measurements look like across the entire spectrum of brain health, a necessary step to bring us closer to establishing these blood tests. We will establish whether these blood tests can tell the difference between people who are healthy and people who have a brain disease by establishing what the normal ranges of these proteins in the Canadian population are. We will also see if these blood tests can differentiate between the different types of dementia, by comparing the protein levels of each type of dementia against our established normal ranges and the ranges from other forms of dementia. If these blood tests prove to be useful for informing us about known brain diseases, we will then investigate whether COVID-19, as a new disease that may have implications for the brain, has biomarker levels similar to the normal population or to those with dementia. This study will ultimately lay the groundwork for establishing blood tests as a way to diagnose dementia and other brain diseases in Canada. Using these blood tests will provide a more accurate and accessible diagnosis, which is important for allowing people to receive drug treatment that targets their specific disease.",,-99,University of British Columbia,77083.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Prognostic factors for disease severity,2022 +P25751,448880,COVID19 persistent symptomatology: an investigation of the metabolomic and proteomic underpinning,"Healthcare workers (HCW) have been the most exposed group to the COVID19 virus. It is of utmost importance to better understand the consequence of infection and its aftereffects on their health, as it may impact their ability to dispense healthcare (see an opinion from NIH director: https://directorsblog.nih.gov/?s=long+covid). The symptomatology associated with COVID19 disease varies significantly. The proportion of patients with prolonged symptoms ranges from 10% to more than 50%, but definitive figures remain uncertain while the symptoms' duration has yet to be defined. To date, no solid lead can explain why some symptoms persist in a specific population and who is at risk of long-COVID. With the worldwide number of infections surpassing 125M patients, the proportion of patients living with COVID19 aftereffects represents a substantial group of individuals. We aim to unravel the biological conditions leading to the occurrence of the post-COVID19 syndrome and uncover potential metabolomic and proteomic biomarkers associated with its presence and severity, and those that predict its persistence and development. We need to gain a better understanding of these aftereffects that affect a sizeable proportion of COVID19-infected individuals. The majority of our HCW cohort will be vaccinated before the conclusion of this project, allowing us to ascertain if vaccination attenuates or exacerbates the observed symptomatology. Additionally, we expect within six months to compare our results with those obtained from cohorts infected with specific SARS-CoV-2 variants. After our project, we will have identified the molecular underpinnings of post-COVID19 symptomatology and their related biomarkers.",,-99,Université Laval,313011.26,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation",Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Characterisation of vaccine-induced immunity,2021 +P25754,481131,Investigating Immunogenicity of Mpox and Mpox vaccine Imvamune in people living with HIV,"Mpox is a disease caused by a poxvirus of the same name. It is predominantly transmitted from wild animals to humans in Central and West Africa. It occurs rarely outside Africa. However, starting May 2022, Mpox outbreaks occurred in many non-African countries in the World including Canada. Quite surprisingly, the disease was not only transmitted from humans to humans but also sexually. In these outbreaks, a very high percentage of people living with HIV (PLWH) as well as men having sex with men (MSM) were infected (up to 51% of cases) suggesting that PLWH and MSM are more vulnerable to the disease. Canada has a large population (> 63000) of PLWH. A poxvirus vaccine, Imvamune, has been approved in Canada for protection from Mpox. PLWH and MSM are vaccinated with this vaccine. Although antiretroviral therapy suppresses HIV replication in PLWH, it does not fully restore immune function. Therefore, the immunogenicity of the Mpox vaccine in PLWH and MSM remains unknown. In simpler words we need to know ability of PLWH to generate antibodies and T cells that protect them from a future Mpox. The present research project is aimed to address this question. It is noteworthy that Imvamune vaccine is based upon a whole live virus. Some of the viral proteins are not relevant to vaccine and may be unsafe for people like PLWH. In this research proposal, we aim to identify T cell epitopes (small fragments of proteins derived from immunity-generating viral proteins), which could enable development of high tech mRNA-based vaccines for Mpox. An additional issue that our research proposal will address is ""how has Mpox evolved to become more efficient in human to human spread and become a sexually transmitted disease?"" Using state of the art technology of sequencing and bioinformatics tools, we hope to find answer to this question. Overall, the results from this project will make Canada better prepared to protect vulnerable populations from future Mpox outbreaks.",,-99,Research Institute of the McGill University Health Centre,375198.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Characterisation of vaccine-induced immunity",2023 +P25758,473350,Characterization of filovirus host factors and small-molecule inhibitors of infection,"Filoviruses are negative strand RNA viruses that can cause severe hemorrhagic fevers in human following zoonotic spillover events. Outbreaks of filovirus diseases are increasing in frequency and our knowledge of the Filoviridae family expended greatly recently with the discovery of new filoviruses in Europe, Africa and Asia that are also potentially pathogenic. While a vaccine against Ebola virus, one of the 5 species of ebolaviruses, is available, it does not protect well against all ebolaviruses and does not protect against other pathogenic filoviruses. Therefore, pan-filoviral antiviral therapy is urgently needed. In this proposed project, we aim to gain a molecular understanding of the filovirus-host cell interactions with the overarching goal of identifying and characterizing pan-filovirus small molecule inhibitors for the development of new pan-filoviral antiviral therapies.",,-99,University of Ottawa,574965.45,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Unspecified,,,,,,,,,Ebola virus disease | Marburg virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P25760,449477,Étude du mécanisme d'action de l'ozanimod dans le contexte de la COVID-19,"As of November 23, 57 million people have been diagnosed with COVID-19, including 1.3 million who have died. In severe cases, there is prolonged lung inflammation that leads to the development of respiratory distress and often death. At the moment, there is no effective medication to treat patients with severe COVID-19. My project is part of the COZI clinical study, where ozanimod, a drug recently approved for the treatment of multiple sclerosis, is being tested to counter severe cases of COVID-19. Indeed, in addition to its beneficial effects in the context of multiple sclerosis, this drug is also recognized as being able to reduce respiratory distress caused by an influenza virus infection. We believe that ozanimod will reduce, in the context of COVID-19, the number and level of activation of white blood cells while reducing inflammatory molecules in the lungs and body. We will therefore compare the white blood cell populations of patients who receive ozanimod versus those who do not receive it and we will analyze the modulation of different inflammatory molecules that are normally increased in the disease. We will also measure the impact of ozanimod on the levels of antibodies against the COVID-19 virus, which are necessary for medium/long-term immunization, in order to ensure that the drug does not harm this process. The data from this project will allow us to better understand the evolution of COVID-19 in hospitalized patients and potentially improve the treatments offered to them.",,-99,Université Laval,13459.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Immunity | Supportive care, processes of care and management | Clinical trials for disease management",2020 +P25761,485603,Lessons Learned from Engage Montréal: Study End Meeting,"Engage is a CIHR-funded Cohort Study of gay, bisexual, and other men who have sex with men (GBM) in Vancouver, Toronto, and Montreal. Since its inception Engage has published 26 research papers and 106 conference abstracts, meeting many of its research objectives including: measuring HIV and other STBBI infection occurrence and their determinants, documenting the uptake of behavioral and biomedical HIV and other STBBI prevention programs, and examining the associations between specific prevention initiatives, the occurrence of recent HIV and other STBBIs, and risk behavior. Engage created the opportunity to foster a rich network of local collaboration between researchers, knowledge users, and community members in Montreal. Data from Engage Montreal has been published by local collaborators in 8 research papers, used to inform local public health responses (e.g. Mpox vaccination intervention), presented in community summary reports and community events (e.g. community engagement committee meetings) and given rise to knowledge translation/transfer (KT) and community mobilization efforts such as infographics. Given that data collection for Engage Montreal concluded in January 2023, a local meeting is needed to be held to gather researchers, knowledge-users and community members to share an updated and complete summary of salient findings from Engage Montreal, fostering discussions on the usefulness of the data within the context of the communities' needs. This meeting will bookend the ""Preliminary Findings"" meeting Engage Montreal hosted in 2018, one year after data collection began. The Cafe is a critical opportunity to direct final KT efforts based on updated data, and to receive input on future studies and interventions. This will ensure that our work will reach knowledge users to improve access to and uptake of HIV/STBBI prevention services among Montreal GBM. The Cafe is planned to take place in person in late 2023 as a series of moderated panel presentations.",,-99,Research Institute of the McGill University Health Centre,4412.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Communication,2023 +P25762,488356,Balancing Infection Prevention and Control Measures with Person-Centered Care to Support Resident Well-Being in Long-Term Care,"The COVID-19 pandemic has had a devastating impact on those who live, work, and visit nursing homes. One of the greatest challenges in the pandemic has been balancing the need to protect our most vulnerable older citizens (residents) in nursing homes and providing individualized care to residents. The purpose of this study is explore the experiences of nursing home staff, residents, and family caregivers around person-centered care when infection prevention and control protective measures were implemented during the COVID-19 pandemic including the present. By gaining their experiences and perspectives, this will allow us to develop recommendations to support resident care and resident well-being while maintaining infection prevention and control protocols in Canadian nursing homes.",,-99,University of Toronto,374211.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2023 +P25763,477337,Balancing Infection Prevention and Control Measures with Person-Centered Care to Support Resident Well-Being in Long-Term Care.,"The COVID-19 pandemic has had a devastating impact on those who live, work, and visit nursing homes. One of the greatest challenges in the pandemic has been balancing the need to protect our most vulnerable older citizens (residents) in nursing homes and providing individualized care to residents. The purpose of this study is explore the experiences of nursing home staff, residents, and family caregivers around person-centered care when infection prevention and control protective measures were implemented during the COVID-19 pandemic. By gaining their experiences and perspectives, this will allow us to develop recommendations to support resident care and resident well-being while maintaining infection prevention and control protocols in Canadian nursing homes.",,-99,University of Toronto,73103.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +P25764,486484,Uncertainty of new intensive care nurses: A descriptive qualitative study,"Due to COVID-19, intensive care units are overloaded with a large influx of patients. However, the number of nurses is not sufficient to provide quality care to affected patients. One solution to this problem is to hire people who are completing their nursing training. Many resources are invested in integrating these newly graduated individuals (NEPs) into intensive care. However, the retention rate is very low since the transition between training environments and intensive care practice is difficult for NEPs. They say they are anxious and feel uncertain. This feeling is described as the inability to predict the outcome of a patient's situation. Faced with uncertainty, NEPs do not feel equipped to make good decisions. This compromises their ability to act and provide quality care to patients whose condition is often unstable. Furthermore, uncertainty causes stress, which leads many PNDs to leave their jobs. Therefore, uncertainty threatens the well-being of PNDs, human resources and the quality of care provided in intensive care. To date, there is no study on the uncertainty of PNDs in intensive care. In this study based on a theory of uncertainty, the feeling of uncertainty among PNDs in nursing will be described with individual interviews. These will allow obtaining the story of a situation causing uncertainty to PNDs with patients in intensive care. Themes will be analyzed to understand the challenges that accompany the transition of PNDs and propose strategies to improve their integration into intensive care and reduce uncertainty.",,-99,Université de Montréal,13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2022 +P25765,460366,"Assessing and Mitigating the Food Insecurity Consequences of COVID-19 Public Health Measures on Marginalized Refugees and Migrants in Canada, Latin America and Africa","Strategies to mitigate the public health impacts of COVID-19 have led to a secondary pandemic of global food insecurity. Our project will 'scale up' our First Round CIHR Grant on the negative impacts of COVID-19 on household food security in Wuhan and Nanjing, China to three additional cities: Quito (Ecuador), Cape Town (South Africa) and Kitchener-Waterloo (K-W) (Canada). The project will have a particular focus on the food insecurity experience of marginalized immigrant and refugee populations during the pandemic and how to build greater resilience post-pandemic. We will undertake a comparative study of the food security and related health impacts of COVID-19 on immigrants and refugees who have settled in these three cities and who come from countries experiencing political and economic crises or natural disasters: in Quito, migrants from Venezuela and Haiti; in Cape Town, migrants from the DRC, Somalia and Zimbabwe; and in K-W, refugees from Afghanistan and Syria. In all three study sites, we have research partners and infrastructure in place as well as ongoing projects on gender violence against migrants (Quito), refugee livelihoods (Cape Town) and the social determinants of refugee health (K-W). The project will be implemented collaboratively by a team of Canadian, South African and Ecuadorian researchers and has the following objectives: (1) to examine the impact of public health containment and mitigation responses to COVID-19 on the food security of marginalized refugee and immigrant groups in urban areas; (2) to assess the similarities and differences between the three sites in terms of access to government, business, and community food security and social protection mechanisms; (3) to provide critical decision-making and pandemic response data to local stakeholders to inform food policy responses; and (4) to strengthen the capacity of Canadian and LMIC researchers and research institutions to respond rapidly to ongoing and future food security shocks.",,-99,"Wilfrid Laurier University (Waterloo, Ontario)",84302.64,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P25769,450587,COVID-19 Impacts on Lived Experiences of Children and Families with Complex Care Needs Residing in the Maritimes: COMPLEX CARE,"Background: Children and youth with complex care needs are one of the most vulnerable populations served by our pediatric health and social care systems. Prior to the COVID-19 pandemic, caregivers of children with complex care needs reported experiencing a number of unmet service and support needs. COVID-19 response measures have resulted in rapid changes to health and social systems across the Maritime Provinces. It is unclear how these changes impacted the needs of families living with complex care needs. Objectives: This research aims to understand how changes to health and social supports implemented during the COVID-19 pandemic impacted children with complex care needs and their caregivers in the Maritimes. We will achieve this by 1) describing how pandemic-response public health measures and/or service changes were implemented, and 2) exploring how children with complex care needs and their caregivers were impacted by these rapid policy and service changes. Methods: To address objective 1 we will conduct an environmental scan to identify public health policy and service changes implemented in the Maritimes during the COVID-19 pandemic relevant to complex care needs. We will supplement our findings with key informant interviews with policy makers to further understand the context of these changes. To address objective 2, we will conduct qualitative interviews with youth and caregivers living with complex care needs in the Maritimes to explore their perceptions and experiences with policy and service changes during COVID-19. Impact: This work will identify policy and service gaps experienced by children with complex care needs and their caregivers in the Maritimes during the COVID-19 pandemic. It will also inform recommendations for policy and service changes during future public health emergencies.",,-99,IWK Health Centre (Halifax),121517.36,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Other,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Indirect health impacts | Social impacts,2021 +P25773,460369,COVID-19 Impacts on Breast Cancer Screening and Care in the Caribbean and marginalized communities in Ontario.,"The COVID-19 pandemic has placed increasing demands on healthcare services globally with cancelled or delayed surgeries, and ICU capacity limits exceeded in many regions. Unfortunately, many Black and marginalized communities in Canada were disproportionately impacted by COVID-19 as they had high mortality rates due to being frontline essential workers (transit drivers, PSWs) and living in multi-generational homes. Globally, many healthcare services, including breast cancer screening, were paused during the initial lockdowns and this may have worsened breast cancer care and outcomes in Black and marginalized communities as they currently have the highest breast cancer mortality rate despite have a low overall incidence of breast cancer. In Ontario and the Caribbean, these populations are at higher risks for aggressive breast cancer and death partly due to lower screening and late tumor detection. Our study seeks to assess breast cancer screening practices before and after COVID-19 lockdown restrictions in immigrant Caribbean and marginalized communities in Ontario and in Barbadian and Jamaican women in the Caribbean. By determining the impacts of COVID-19 on breast cancer screening and care during the pandemic among these groups of women, our findings will help decrease the known gaps in breast cancer care and outcomes, and inform cancer screening and cancer care policies globally for millions of marginalized women diagnosed with breast cancer.",,-99,McMaster University,401556.18,Human Populations,Black,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25776,468195,Stakeholder Engagement to Increase Access of Mental Health and Substance Use Services Among Equity Deserving Groups,"Those who identify as Indigenous and/or two-spirit, lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, and additional sexual orientations and gender identities (2SLGBTQIA+) are at a higher risk of struggling with mental health concerns. COVID-19 has highlighted challenges that already existed in accessing mental healthcare for people who identify as Indigenous and/or 2SLGBTQIA+. Indigenous Peoples often experience a cultural clash as well as systemic racism when accessing care through mainstream services. Those from the 2SLGBTQIA+ community are often faced with discrimination as well as care that invalidates a person's gender identity and/or sexual orientation when accessing services for mental health concerns. The proposed project aims to understand current barriers in accessing care through the Mental Health and Addiction Program at St. Joseph's Healthcare Hamilton (SJHH) for those who identify as Indigenous and/or 2SLGBTQIA+. Our proposed project will involve at least six meetings with people who may be interested in receiving mental health services and are from Indigenous community organizations as well as those from 2SLGBTQIA+ organizations in the community to hear their perspectives on barriers to care through the Mental Health and Addiction Program at SJHH. The findings from this proposed project will help to plan and develop programs through the Mental Health and Addiction Program at SJHH that will better serve those who are Indigenous and/or 2SLGBTQIA+. This work could be expanded to other equity-deserving groups in the future to create equitable and accessible mental healthcare for all.",,-99,St. Joseph's Healthcare Hamilton West 5th Campus (Ontario),25920.35,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Health service delivery,2022 +P25777,465729,Enabling Safer Care: Evidence-Based Implementation of Escalation of Care Strategies in an Academic Healthcare System,"Each year, 70,000 patients are harmed in hospital, despite decades of trying to make the healthcare system safer for them. This harm is not intentional and can be a result of miscommunication between patients' healthcare team. Sometimes, patients' health worsens and if that isn't noticed and reported by healthcare workers it is called a failure to escalate care. Escalating care means a healthcare worker notices a change in a patients' condition and reports it. Sinai Health (SH) is committed to making healthcare safer for their patients by trying to eliminate harm from not escalating care. SH began addressing escalation of care, but paused this work to respond to the pandemic. My project will implement escalation of care strategies at SH to provide better and safer care. The healthcare system changed because of COVID-19, so I will first update our escalation of care strategies to account for the latest research on COVID-19 and review other hospitals' strategies to ensure that SH is meeting the same standards. One reason why healthcare workers don't escalate care is because they are afraid of being criticized or humiliated. Psychological safety (PS) is defined as how safe people feel about speaking up at work. PS is important for escalating care because without it, healthcare workers might not speak up. Also, speaking up is harder when managers and workers don't feel the same level of PS. I plan to interview healthcare workers and their managers individually to find out about their PS to see if it matches and see if that changes how they escalate care. The COVID-19 pandemic has been difficult for healthcare workers, so I will also ask questions about how the pandemic may have changed their feelings around escalating care. Combing the knowledge from my interviews with the updated escalation of care strategies, I will create an implementation plan for SH. I will share my work with SH management, SH's partner organizations and with the academic research community.",,-99,Sinai Health System (Toronto),27291.49,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25778,468881,Exploring the experiences of small and rural municipalities during the COVID-19 Pandemic to identify enabling supports and structures that will strengthen response to future disruption,"In Canada, geography is a determinant of health: people living in rural and remote areas experience poorer or different health outcomes than their urban counterparts. While approximately 29% of the Canadian population lives in small and rural areas, this project will focus on communities in Northern Ontario with fewer than 10,000 residents. Rural communities have lower rates of self-reported health, lower rates of physical activity, and higher rates of overweight and obesity, and smoking. They also have lower rates of depression and higher sense of social cohesion. In Canada, mortality from preventable causes increases with remoteness. The COVID-19 pandemic has uniquely affected rural communities; although impacts related to substance use, mental health, food security, gender-based violence, and financial security have been documented across Canada, each of these was amplified or at least experienced differently in rural communities, as were disparities related to inequitable access to broadband Internet. This research study asks: what enabling supports and structures would help small/rural communities in Northern Ontario to more effectively respond to disruption? Using a pragmatic and a systems approach, this project will employ a qualitative, case study research design including semi-structured interviews, thematic discourse analysis, and a participatory workshop to address the research question. Results will contribute to strengthening Canada's public health system by identifying opportunities to better support local governments in small and rural communities to promote health and wellbeing.",,-99,University of Guelph,62728.27,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25779,450263,Persistence and potency of naturally-occuring and vaccine-induced memory T cells to SARS-Cov-2 variants,"The COVID-19 pandemic has led to the infection of more than 135 million people world-wide and the death of 4 million of these individuals. The development of vaccines gives us hope that we will ultimately control the pandemic. It remains to be demonstrated if mass vaccination can induce prolonged protection against reinfection in vaccinated individuals, and thus prevent virus transmission and dissemination world-wide. This collaborative project with the Coalition for Epidemic Preparedness Innovations (CEPI) proposes to evaluate if immune cells called T cells are generated and maintained in vaccinated individuals, as these T cells are essential for prolonged protection against SARS-CoV-2, the virus that induces COVID-19. Further, we propose to test if these T cells develop long-lasting immune memory and are protective against the novel and more infectious variants. Finally, we hope to identify which memory T cells are truly protective and develop simple surveillance tools to follow these memory T cells in infected or vaccinated individuals. Collectively, this project will support the development of effective and protective vaccines against coronaviruses of pandemic potential, including SARS-Cov-2.",,-99,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",324340.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +P25782,499020,Wastewater-Based Surveillance Integration with Health Decision-Making: Protection Against Health Threats and Promotion of Health Equity,"Wastewater-based surveillance (WBS) has shown to be an early warning system of health threats, an economic system that withstands high testing demands during pandemics and also an anonymous surveillance system that is adaptable for underrepresented and vulnerable communities. These capabilities have led to the installation of over 4600 WBS testing locations around the world, including 260 locations in Canada, since the start of the COVID-19 pandemic. Despite this rapid growth in WBS testing locations, limited integration between WBS knowledge and health decision-making currently exists due to the notable lack of standardized WBS data, ability to ensure data reliability and guidance on how to interpret WBS data for health actioning. The research outcomes will be built upon my team's experience in WBS and in particular our success in building a public health integrated WBS system with Ottawa Public Health in the city of Ottawa during the COVID-19 pandemic. The proposed Applied Public Health Chair research program will develop best practice guidelines, a data pipeline and implementation framework to ensure WBS data reliability and fully integrate WBS with health and policy decision-making to safeguard against future pandemics, promote health equity in Canada and around the world, and foster One Health concepts to minimize the impact of climate change-induced health threats. My research team will collaborate closely with 9 engaged health decision-maker partners, 5 community advisory committees comprised of individuals with lived experience from underrepresented and vulnerable populations and international collaborators, international WBS working groups and global WBS surveillance programs to produce research outcomes that are generalizable across Canada and the world.",,-99,University of Ottawa,851777.48,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P25784,454557,"Mental health, risk behaviours and access to support services: the experience of postsecondary students from CLOSM in Manitoba and New Brunswick","Young adults in postsecondary education are experiencing a major life transition; many are likely to develop mental health disorders, risky behaviors, and experience academic difficulties. The COVID-19 pandemic has exacerbated the difficulties related to the formation of a social network, having a negative impact on their mental health. Young people do not often use professional support services due to a lack of awareness of the availability of services and barriers to access. Through an online survey, this study aims to describe the experience of the undergraduate student population of two Canadian Francophone universities in official language minority communities (OLMCs) (Université de Saint-Boniface and Moncton) with regard to mental health and access to psychosocial support services, substance use, road safety, violence, sexual practices, and addiction to personal electronic devices. The data will be analyzed by age, gender, ethnolinguistic identity profile (first- and second-language Francophones; international Francophones) and site (rural/urban context and Francophone density), as these factors can influence health and well-being. Focus group interviews will be used to disseminate and validate the results of the student survey and to identify the barriers faced by these young people in accessing support services on campus and in the community in the official language of their choice. The data collected will underpin the formulation of recommendations on how to promote their access to available support services. These recommendations will be shared with collaborators and policy makers in order to support the development of these young people, who are essential to maintaining the vitality of OLMCs.",,-99,Université de Saint-Boniface (Manitoba),47618.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25789,473344,Developing intranasal dsRNA molecules as broadly effective therapeutics against highly pathogenic coronaviruses,"Long double-stranded (ds) RNA molecules are produced by viruses during their replicative cycle. These dsRNA molecules are long (1000s of base pairs) and contain viral genome sequence. In vertebrates, it was thought that viral dsRNA's major role was to stimulate host antiviral type I interferons (IFNs). The IFN response is a broad-spectrum antiviral response, stopping the virus in its tracks. It is potent, but also energetically costly, shuts down the cell's ability to make any protein, and induces side effects such as inflammation. In invertebrates and plants, long dsRNA does not induce IFN, but is used as a substrate for RNA interference (RNAi). RNAi uses an enzyme, Dicer, to cut the viral dsRNA into ~20bp pieces called short interfering (si)RNAs, which are loaded into RISC, where an mRNA whose sequence matches the siRNA is found, bound, and sequestered or degraded. In this RNAi pathway, it is the viral sequences that are targeted for degradation specifically, making it less energetically costly with lower side effects. We have found that long dsRNA can be used as a substrate for RNAi in vertebrate cells if used at a dose that is below the threshold to induce IFNs. Using this strategy, dsRNA containing coronavirus sequences knock down coronavirus (CoV) replication in human cells. The proposed project has 3 aims: (1) identify highly conserved CoV genomic sequences to develop pan-CoV dsRNA sequences that are optimized for Dicer recognition, (2) validate efficacy of dsRNA molecules in inhibiting CoV replication in human airway cells, either 'naked' or encapsulated in a lipid nanoparticle or virus-like particle, and (3) validate the antiviral effects of long dsRNA molecules in the airway using the golden Syrian hamster model of SARS-CoV-2. This project will develop a first-in-its-class pan-coronavirus therapeutic to be used prophylactically to protect the global population from the current SARS-CoV-2 pandemic as well as emerging CoVs.",,-99,"Wilfrid Laurier University (Waterloo, Ontario)",76662.06,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2022 +P25793,484647,Understanding the intersectional impacts of living through the COVID-19 pandemic on the mental health and sexual and reproductive health (SRH) of 2SLGBTQ BIPOC communities,"This project will examine the impacts of living through the COVID-19 pandemic on the mental health and sexual and reproductive health of 2SLGBTQ BIPOC communities. Working with the Community Based Research Centre, and their ongoing quantitative and qualitative research with 2SLGBTQ communities across Canada, an intersectional social justice approach will guide the analysis to understand better the shared drivers of health (in)equity and health system experiences. In studying multiply marginalized participants there may be new conclusions that can be drawn about the differential experiences across these groups to inform future health service delivery and health policy planning that improve access and reduce inequities.",,-99,Community-Based Research Centre (Vancouver B.C.),39893.77,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25798,486579,Surviving to COVID-19 after a stay in the Intensive Care Unit (ICU): Stress and coping experiences of patient/family dyads,"The COVID-19 pandemic led to a number of quick adaptations to hospital policies. Restrictive regulations may have interfered with interaction and decision-making between Intensive Care Unit (ICU) patients and their families. By restricting the number of allowed visitors and the hours of visitation, the pandemic has imposed an extra hardship on patients and their families who require lengthy hospitalizations in ICU. This study aims to better understand the unique stress and coping processes experienced by COVID-19 survivors and their families as pairs following an ICU stay. No research has examined the diverse viewpoints of COVID-19 survivors and families as a pair following an ICU admission; pairs provide richer family-centered viewpoints. A mixed-methods study will allow us to uncover various unique patient-family viewpoints in a comprehensive manner. A range of 10-12 patient-family pairs recruited from three Quebec ICUs using interviews and brief questionnaires on stress-related symptoms and fear of COVID-19. These methods are designed to offer insight into the specific challenges and needs of COVID-19 ICU patients and their families, what they require, and how patients and families cope with challenges related to an ICU stay. The study will explore whether needs differ according to factors such as age, sex and gender. Given the severity of the COVID-19 pandemic in the Canadian community, it is critical to gain a thorough understanding of the unique patient-family stress and coping experiences with COVID-19 and ICU hospitalization to identify unmet needs and appropriate interventions, to provide equitable care and to improve recovery outcomes. The findings will inform health managers and policymakers in pandemic management.",,-99,McGill University,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Post acute and long term health consequences | Approaches to public health interventions",2022 +P25804,481148,Trauma in Male and Female British Columbia Paramedics: The Effect of COVID-19 on Workplace Trauma,"Extant research suggests that paramedics, and other first responders, are at an increased risk of developing a trauma and stress related disorder such as posttraumatic stress disorder (PTSD) due to the high rates of workplace traumatic events they experience. However, paramedics are now experiencing increased uncertainty and unprecedented circumstances due to the COVID-19 pandemic that began in Canada in early 2020. This investigation looks to determine how these unprecedented times has impacted the experience of workplace traumatic experiences in BC paramedics. Additionally, given the increased rate that women develop PTSD from traumatic experiences compared to males, this investigation will determine the different needs and rates of PTSD in male and female paramedics. Through a combination of quantitative survey, and qualitative interviewing, this study will provide crucial information for understanding the experiences of BC paramedics during the ongoing COVID-19 pandemic and for identifying and building the supports necessary to prevent and treat PTSD in paramedics.",,-99,"Simon Fraser University (Burnaby, B.C.)",13724.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25806,480699,Amplifying the contributions of community health workers to health systems resilience: An engagement and planning process in the Philippines,"Throughout the COVID-19 pandemic, community health workers have been crucial to pandemic response and recovery. Often embedded within resource-constrained communities, these workers have been on the 'frontlines' of addressing compounding health emergencies (e.g., COVID-19 pandemic and extreme weather events) in many low- and middle-income countries including the Philippines. Despite the recognition of their essential role, there is a gap in understanding how this work contributes to the resilience of health systems. Further, there is an opportunity to explore priorities and strategies for supporting these crucial actors in the health workforce amid compounding health emergencies. This engagement and planning process aims to: (1) engage with representatives from Philippines-based civil society organizations and government to understand the current role of community health workers in the context of compounding health emergencies and how this work can be supported; (2) synthesize findings, including conducting a scoping review, to identify research gaps and future opportunities; and (3) co-develop a detailed research plan, grounded in an existing partnership with a Philippines-based non-governmental organization. Overall, this engagement and planning process will build a critical foundation for subsequent collaborative and community-based research that aims to amplify the contributions of community health workers and support them in responding to current and future health emergencies.",,-99,University of Waterloo (Ontario),15007.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health workforce,2023 +P25808,494280,The Socio-economic Impact of the Post-COVID-19 Condition in the Canadian Context,"As the COVID-19 pandemic continues, many people are experiencing long-term symptoms and health problems following SARS-CoV-2 infection, a condition known as Post-COVID-19 Condition (PCC) or Long COVID. According to a 2022 national survey, approximately 14.8% of adult Canadians with confirmed or suspected COVID-19 infections report experiencing longer-term symptoms. Moreover, nearly half (47.3%) of those individuals with PCC report that their symptoms persist for a duration of one year or more. Recent studies show that the likelihood of being diagnosed with PCC varies among populations. For instance, people from certain racial and ethnic groups are more likely than other groups to experience certain symptoms linked to PCC. Simply observing health disparities between groups does not necessarily explain the variations in PCC or how to reduce them. However, investigating the root causes behind why socially and economically disadvantaged groups face higher PCC risks can help inform policy interventions that reduce health disparities. Our five-year project aims to create new knowledge about inequitable health disparities caused by PCC. We expect to answer questions such as: to what extent does access to healthcare, housing quality, or gender account for disparities in the prevalence of PCC in Canada? This project seeks to improve our understanding of PCC by investigating and measuring the impact of social determinants of health on PCC variation among socially and economically disadvantaged subgroups of the population and identifying patterns and variations in disparity measures related to PCC, specifically within marginalized communities. This research project will generate knowledge and evidence that help with the development of effective interventions by policymakers that can reduce health inequities due to PCC.",,-99,"York University (Toronto, Ontario)",73558.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Policy research and interventions | Indirect health impacts | Social impacts,2023 +P25810,489495,Engineered Lipid Nanoparticle miRNA-therapy Options for ARDS,"Severe and acute respiratory distress syndrome (SARS/ARDS) is an important and costly medical problem, for which there are few, or no treatments. In the case of COVID-induced SARS, steroids and immune modulating drugs may not be effective for all and have important side-effects. Having new treatments for ARDS/SARS would significantly reduce suffering and unburden the health-care system. We have discovered new roles for two microRNA (miR) - small RNAs that regulate protein levels. miR-193b-3p is increased in SARS/ARDS and it acts to disrupt 2 proteins that are important for the function and defense of the lung: (1) Occludin - contributes to cell function and prevents fluid from flooding the airspaces during virus or bacterial severe infections. (2) Surfactant protein C - prevents airspaces from collapsing during breathing. Both of these proteins are also involved in interacting and killing of pathogens or preventing their dissemination, and modulating immune responses. The second is miR-187a-3p. This miR is usually abundant in healthy individuals, but its levels fall during illness. miR-187a-3p is anti-inflammatory and it acts by decreasing levels of inflammatory mediators Tumor Necrosis Factor alpha and interleukin 6 - very important in SARS/ARDS. To translate our new research to humans, we have made two lipid nanoparticle (LNP), similar to the ones used for the Moderna and Pfizer vaccines. One contains and inhibitor of miR-193b-5p and the other a mimic of miR-187a-3p. In pilot animal studies, we delivered these medications in the blood through an intravenous injection. We show they reach the lungs and reduce the severity of ARDS without causing harm. Here we want to advance our work towards developing these therapies. An important step is to study them for thoroughly in animal models. We propose to use three models of ARDS - caused by influenza virus, bacteria and COVID virus. If successful, our work may lead to a novel treatment for ARDS.",,-99,Unity Health Toronto,270108.05,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P25811,460236,A mixed-methods study to develop a jurisdiction-level resource allocation framework to guide the use of triage and triage-avoidant strategies during an overwhelming surge in demand for critical and acute care.,"During the COVID-19 pandemic, many jurisdictions experienced overwhelming surges in demand for critical care. Some developed critical care triage frameworks or protocols in preparation for this eventuality, but most were able to avoid overt bedside triage (so far) through a combination of effective public health measures, reducing scheduled surgical care, and by increasing capacity through reallocation of existing staff, supplies and beds to provide the ICU care required, or moving patients to other hospitals (often some distance away) where ICU capacity still existed. These triage-avoidant strategies-strategies adopted across the health sector and via other public health and social measures-have led to unintended and not yet fully understood negative consequences for patients, family members, staff and healthcare organizations. Our current triage protocols are focused on patient-level decisions and do not address the consequences of system-level prioritization decisions (i.e., triage-avoidant strategies) that are made in a pandemic. To inform these decisions, we would benefit from a better understanding of their potential consequences. This question has an equity dimension, as both triage protocols and triage-avoidant strategies may have disproportionate effects on populations marginalized by race, disability, socioeconomic or health status, and other factors. Accordingly, in this project, we intend to collect and analyze health services data from Canada and use key stakeholder input to help interpret and contextualize this data. Ultimately, we plan to develop a jurisdiction-level resource allocation framework that could help decision-makers improve outcomes and mitigate the potentially disproportionate effect of future pandemics on marginalized populations.",,-99,Bruyère Research Institute,402931.14,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25814,459196,Structural harms and COVID-19 policy responses in Manitoba: Exploring the experiences of Red River Métis,"Why this research is needed: Systematically marginalized populations, such as First Nations/Métis/Inuit (FN/M/I), have been greatly affected by COVID-19 in Canada. This is why people identifying as FN/M/I were prioritized for COVID-19 vaccines. This policy was adopted Canada-wide, except in Manitoba. In Manitoba, only First Nations Peoples were prioritized for COVID-19 vaccines. Inuit and Métis Citizens were to access COVID-19 vaccines following age-eligibility criteria like all other Manitobans. This policy changed in May 2021 in acknowledgement of the ""impacts of colonization on all Indigenous people in Canada"". Vaccines were handled differently during H1N1, where only Manitoba prioritized people of Indigenous Ancestry (FN/I/M) for H1N1 vaccine in Canada. Manitoba's COVID-19 vaccine policy has had a negative impact on vaccine uptake by the Red River Métis. In this project we aim to study: 1.Ongoing COVID-19 vaccine decision-making processes among Métis Citizens; 2.Harms (e.g. COVID-19 infection rates, health service use for COVID-19, lower vaccine uptake) created by a racist policy that disadvantaged Métis relative to all other Manitobans; 3.The impact on possible COVID-19 cases if Red River Métis had been prioritized for vaccination earlier in the pandemic; and 4.Long-term consequences and possible loss of trust among Métis in provincial health systems. Methods: We will carry out focus group discussions with Red River Métis (obj 1, 2, 4) to examine Métis experiences given the provincial public health COVID response, and use whole-population administrative health and COVID vaccination data, updated monthly, to compare Métis experiences to all other Manitobans (obj 2, 3). Impact: As we enter the fourth wave, we need to document the experiences of Red River Métis relative to all other Manitobans. Only then might we be able to better understand how we can close the gap in Métis vaccine uptake.",,-99,University of Manitoba,394183.55,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions | Indirect health impacts | Social impacts | Other secondary impacts,2021 +P25818,454092,Vaccine hesitancy: Understanding to act better,"Vaccination is a highly effective public health measure to prevent disease. However, more and more people have significant fears and doubts about vaccines. It is estimated that one in three people are hesitant to get vaccinated or to have their child(ren) vaccinated. This phenomenon is called ""vaccine hesitancy"". Hesitant people may refuse certain vaccines or delay vaccination and these behaviours have been associated with outbreaks of vaccine-preventable diseases, such as measles. This situation is particularly concerning in the context of COVID-19 vaccination, as vaccine hesitancy could undermine the success of the vaccination campaign. This program aims to better understand why people are hesitant to get vaccinated or to have their child(ren) vaccinated, as well as to examine why some health professionals are hesitant about vaccination. In addition, work will be conducted to develop and evaluate solutions to reduce fears and doubts about vaccination and promote informed vaccination decisions. Various qualitative (interviews, ethnographic research) and quantitative (surveys) research projects will be carried out to do this.",,-99,Université Laval,897460.35,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P25819,449337,Influence of group and online prenatal education services and the COVID-19 context on different indicators related to breastfeeding,"Breastfeeding is important for the health of mothers and their infants. It contributes in particular to the strengthening of the latter's immune system. As a second wave of the global COVID-19 pandemic rages in Canada, we still do not know the impact of this crisis on breastfeeding. According to the theoretical model of breastfeeding self-efficacy (BSE), the development of mothers' confidence in their ability to breastfeed could be influenced by the context of this crisis and by the availability of prenatal education services. With this in mind, it is essential to know the influence of group prenatal education (GPE) and online prenatal education (OVE) services, as well as the context of COVID-19 on breastfeeding. Purpose: To measure the influence of GPE/OVE services and the context of COVID-19 on various indicators related to breastfeeding among expectant and new mothers of a first child. Method: Predictive correlational study conducted using data from a cohort study of 863 women pregnant with a first child, some of whom were exposed to the Quebec context of COVID-19 at the end of pregnancy and/or in the weeks following birth. Different analysis models will be used to estimate the influence of educational services and the COVID-19 context on the intention to breastfeed, the evolution of the SAEA, the initiation and duration of breastfeeding. Impact: The results will be able to guide decision-making aimed at better integration of educational and breastfeeding support services throughout the perinatal trajectory, in the context of a pandemic, here and internationally.",,-99,Université Laval,13459.8,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25820,454459,Assessing the effects of a self-stimulation protocol with(out) sexual devices on sexual function and mental health,"Depression, anxiety, and stress (DAS) are global mental health concerns with negative relations to sexual function. Recent studies show that many people have turned to technology to fulfill their intimate needs and alleviate the psychological distress of the COVID-19 pandemic. This includes the greater use of sexual devices, like vibrators and masturbators. Such sex toys are commonly used and recommended in therapy. They have the potential to relieve stress and enhance sexual functioning (e.g., arousal, lubrication, orgasm, and pleasure). Yet, there is a lack of experimental research on the therapeutic use and effects of sex toys. Moreover, no study has experimentally examined their effects on mental health. Thus, this project aims to experimentally assess the effects of a sexual self-stimulation protocol with(out) sex toys in the general adult population. It is hypothesized that a 6-week sexual self-stimulation protocol will improve sexual functioning and reduce DAS in participants when compared pre- and post-intervention, with the experimental group of sex toy users (EXP) exhibiting higher sexual function and mental health post-intervention than the control groups of non-users (CTL1) and individuals who do not follow any protocol (CTL2). A sample of 60 adults (30 vulva-vagina owners, 30 penis owners) will be randomly assigned to three conditions. EXP will self-stimulate to orgasm with a vibrator or masturbator at least three times a week. CTL1 will follow this protocol but without devices. CTL2 will not follow any protocol. The sexual function and mental health of participants will be assessed at baseline and every 2 weeks with follow-ups at 3 and 6 months using genital thermography and online health questionnaires. This research project will help determine whether sex toys can enhance sexual function and mental health. It will also contribute to the development of evidence-based, standardized treatment protocols that employ such devices in clinical interventions.",,-99,Indiana University (Bloomington),118464.76,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Belize,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25822,454684,"Engagement, risk profiles, and effects on cognitive function of older adults participating in a multidimensional educational intervention: The Brain Health Support Program","With the aging of the population in Canada, a growing number of older adults are suffering from severe memory problems such as Alzheimer's disease. These memory problems could be partly prevented by improving lifestyle habits, social environment, mental health and the health of blood vessels, vision and hearing. Due to the COVID-19 pandemic, data are needed to measure the effectiveness of educational programs to be done remotely from home, using the internet, with the aim of reducing severe memory problems. My research project will consist of evaluating the effect of a distance educational program on memory and the ability to learn and speak. The decline in these abilities is among the first symptoms of severe memory problems. The program was designed by a team of recognized Canadian researchers from several disciplines. It will focus on the definition of memory problems, physical activity, intellectual activities, diet, sleep, social environment, mental health and the health of blood vessels, vision and hearing. Participants will be between the ages of 60 and 85 and recruited from 12 sites across Canada. They will follow this program remotely for one year, for 40 minutes per week. Several measurements will be taken throughout the project. This study will provide a better understanding of the importance of acting on several lifestyle habits and the health of older adults in order to increase the chances of delaying the onset of severe memory problems such as Alzheimer's disease. It will also evaluate the effectiveness of an educational program done completely remotely, which can be carried out during a pandemic and at low cost.",,-99,"CIUSSS du Centre-Sud-de-l'Île-de-Montréal (Montréal, Québec)",106618.28,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25823,429629,PRevention of COVID-19 with high dose Oral Vitamin D supplemental Therapy in Essential healthCare Teams (PROTECT),"During the COVID-19 pandemic, despite personnel protection equipment, healthcare workers are 10 times more likely to contract the infection due to their exposure to patients and co-workers with unknown or confirmed COVID19 infection. Any one withdrawn due to infection has an amplified negative impact on care delivery, further increasing the burden on those remaining and on our healthcare system. Studies have shown that Vitamin D supplementation decreases the risk of common respiratory illnesses by about 20%, particularly in those with lower vitamin D levels. Lower Vitamin D levels is a common occurrence among Canadians, particularly in the fall and winter, that is, at the expected of the second wave of infection. Whether high-dose vitamin supplementation can help decrease the risk of COVID 19 infection in health care workers is yet to determined. In this 16-week randomized clinical trial to be started in September 2020, 2414 healthcare workers in the greater Montreal area will be allocated by chance to receive: (i) a high bolus dose of vitamin D followed by weekly doses of vitamin D or (ii) placebo bolus and placebo weekly dose, for 16 weeks. Every two weeks, participants will perform a nasal swab to be send to analysis. This study will examine whether healthcare workers receiving vitamin D have a lower risk of COVID-19 infection, milder infection, and/ or a shorter infection duration, compared to the control group. If vitamin D proves effective to decrease COVID 19 infections, severity, and duration, it may be the cheapest, most easily applicable approach (in addition to social distancing and personal prevention equipment) to prevent COVID-19 infection in at-risk healthcare workers. If the benefit also translates in fewer and shorter withdrawals from the workforce, it may consubstantially reduce the burden on healthcare system and ensuring sufficient healthcare workforce to better tackle the current pandemic.",,-99,"Centre hospitalier universitaire Sainte-Justine (Montréal, Québec)",53353,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase)",2020 +P25824,432393,"ATTACH™ & VID-KIDS: Rapid User-Informed Web and Mobile Interface Development, Adaptation and Pilot Testing to Support Children's Mental Health and Development.","Toxic stress undermines parent-child relationship quality and puts children at risk for mental, emotional and behavioural (MEB) health and development problems. The COVID-19 pandemic has placed additional stressors on vulnerable families and dramatically impacted the delivery of support services and related research. Our aim is to build on the success of two CIHR funded in-person (home or clinic) intervention programs designed to improve parent-child relationship quality and child MEB health and development by rapidly pivoting to user-engaged design and pilot testing of two unique virtual delivery programs. ATTACH™ (Attachment and Child Health) is designed to help parents affected by toxic stress (parental depression, addictions, family violence, low-income) improve their reflective function (RF) or capacity to understand their own and their child's mental states, which can strengthen parent-child relationships and buffer the impacts of toxic stress on children. VID-KIDS (Video Feedback Interaction Guidance Program for Depressed Mothers and their Infants) is designed to help mothers with postpartum depression to be sensitive and responsive to their infants, an ability undermined by the symptoms of depression, in order to promote healthy child development. Using integrated knowledge transfer and co-design approaches, we will further develop and pilot test both virtual delivery programs for real world implementation, by evaluating the impact of the beta prototypes on children's MEB health and development. For VID-KIDS, impacts on maternal depression will also be assessed and for ATTACH™, RF will also be measured. This project will set the stage for two future tri-council randomized controlled trial (RCT) grants, expanding our research into user-engaged technology-enabled delivery of urgently needed community mental health interventions, and allowing us to rapidly scale up these parent training programs to reach a greater number of vulnerable Canadian families.",,-99,University of Calgary,145993,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25832,486640,Canadian Post-secondary Students' Experiences of Continuing Stress and Psychological Distress After the COVID-19 Pandemic: a Cross-Sectional Trend Analysis,"Canadian post-secondary students are experiencing increased mental health-related concerns, including stress, psychological distress, and symptoms of mental illnesses. This high-risk population is subject to many stressors due to the post-secondary setting, ongoing brain development, and increased stressors with the onset of the COVID-19 pandemic. The rates of symptoms of anxiety and depression among post-secondary are higher compared to the general population and continue rise throughout the pandemic. Previous research has revealed the need for further studies concerning mental health and stress in this population. The majority of existing studies were conducted early on in the pandemic, therefore the proposed study will focus on the mental health of post-secondary students starting in 2024, allowing for the assessment of the residual effects of COVID-19. The primary objective will be to describe trends in post-secondary stress and mental health at this time in a Canada-wide sample. This will be a cross-sectional study with data collected at multiple time points. A trend analysis will thus be employed to compare results for each of the variables. Measures will include validated mental health questionnaires such as the psychological distress scale (K-10), the Brief Resilience Scale (BRS) and the perceived stress scale (PSS-10). Respondents will also be asked a variety of demographic questions (i.e., sex, school, student status). Analyses will be conducted to determine whether prevalence estimates of each of the measures changed over time. The proposed study will contribute to the expanding body of literature on the subject of post-secondary mental health, and fill gaps left by previous research.",,-99,University of Waterloo (Ontario),13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25833,480730,129Xe Magenetic Resonance Imagind-based Phenotypes of Long COVID: A multi-center Evaluation,"Long C0VID symptoms are heterogeneous overall, however respiratory symptoms make up a large proportion of the persistent effects that people may experience following a C0VID infection. The C0VID-19 pandemic has driven a considerable wave of new patients that now require care of respiratory specialists, yet there remains a limited understanding of the lung pathophysiology that drives these respiratory symptoms. We further suspect that the respiratory pathophysiology itself is heterogeneous between patients, therefore we derived imaging-based phenotypes of long C0VID. This work directly aligns with the ICRH mandate by developing a better understanding of the respiratory pathophysiology of long C0VID, towards improving care for these patients",,-99,University of British Columbia,1107.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2023 +P25834,488141,Investigating the Relationship Between Musculoskeletal Post-COVID Sequelae and Acute COVID-19 Characteristics and Co-morbidities,"Post-acute COVID Syndrome (PACS), also known as Long COVID refers to the persistence of symptoms after acute COVID infection and there is yet to be a strong scientific consensus on how exactly it may be characterized. Musculoskeletal (MSK) symptoms such as myalgia, arthralgia and fatigue/muscle weakness are some of the most frequently reported symptoms of PACS. Research indicates that the severity of post-COVID sequelae observed in patients is associated with the presence of pre-existing comorbidities. Some literature also speculates that hospitalization and ventilation may play a role in the occurrence of PACS symptoms. The proposed research aims to investigate the relationship between musculoskeletal post-COVID sequelae and the presence of pre-existing comorbidities in adults who were confirmed positive for COVID-19. The study will be a retrospective cohort study that utilizes clinical data from the National COVID Cohort Collaborative (N3C) data enclave on adult patients in the United States who have been diagnosed with COVID-19. Sex-specific multivariate logistic regression models adjusting for baseline covariates will be utilized to test associations between musculoskeletal symptoms and both the comorbidities and the characteristics of COVID-19 infection (e.g severity, duration, and care). Additionally, a survival analysis will be used to analyze time to the occurrence of MSK symptoms, adjusting for baseline covariates. Primary outcomes will be incident musculoskeletal post-acute COVID sequelae including myalgia, arthralgia, and fatigue. Through investigating this relationship, the proposed research aims to fill in some of the many knowledge gaps surrounding COVID-19 infection, particularly, its longer-term health implications.",,-99,University of Western Ontario,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2022 +P25835,472835,Infant and child health outcomes following SARS-CoV-2 infection in pregnancy,"New data suggest that there may be lasting effects of SARS-CoV-2 infection in pregnancy on both mothers and their children. Because of the relative recency of the pandemic, we are only now able to start investigating these issues. Current information comes from small studies that lack detailed information on the timing of COVID-19 diagnoses in pregnancy and the presence or severity of symptoms. Existing Canadian data can be used to address these knowledge gaps. This project will make use of routinely collected hospital, administrative and public health data in Ontario to investigate the long-term effects of SARS-CoV-2 infections in pregnancy on child health and development. We will establish a large dataset of mother and infant pairs with and without documented COVID-19 in pregnancy. Within this dataset, we will investigate the association between SARS-CoV-2 infection in pregnancy and child risk of hospitalization, emergency department visits, and infection-related health care use. We will also assess the association between SARS-CoV-2 infection in pregnancy and child risk of hearing and sight deficits, speech and language delays, and neurodevelopmental disorders. In our analyses, we will account for the timing of SARS-CoV-2 infection during pregnancy, disease severity, presence of symptoms, postnatal infections, and maternal and child vaccinations. With this approach, we will have the breadth and depth of detail necessary to address critical questions about the impacts of COVID-19 on fetal development and child wellbeing and the protective role of COVID-19 vaccines for reducing risk of adverse health outcomes. We will use our findings to help inform maternity and child health care providers, health agencies and Canadian families about the potential long-term risks associated with COVID-19 in pregnancy, and support early screening and intervention of at-risk children to give them the best possible starts in life.",,-99,Ottawa Hospital Research Institute,76662.06,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P25836,494496,Infant and child health outcomes following SARS-CoV-2 infection in pregnancy,"New data suggest that there may be lasting effects of SARS-CoV-2 infection in pregnancy on both mothers and their children. Because of the relative recency of the pandemic, we are only now able to start investigating these issues. Current information comes from small studies that lack detailed information on the timing of COVID-19 diagnoses in pregnancy and the presence or severity of symptoms. Existing Canadian data can be used to address these knowledge gaps. This project will make use of routinely collected hospital, birth registry and public health data in Ontario to investigate the long-term impacts of COVID-19 in pregnancy on infant and child health. We will establish a large dataset of mother and infant pairs with and without documented COVID-19 in pregnancy. Within this dataset, we will investigate the association between SARS-CoV-2 infection in pregnancy and child risk of hospitalization, emergency department visits, and immune-related health care use. We will also assess the association between SARS-CoV-2 infection in pregnancy and child risk of hearing and sight deficits, speech and language delays, and neurodevelopmental disorders. In our analyses, we will account for the timing of SARS-CoV-2 infection during pregnancy, disease severity, presence of symptoms, postnatal infections, and maternal and child vaccinations. With this approach, we will have the breadth and depth of detail necessary to address critical questions about the impacts of COVID-19 on fetal development and child wellbeing and the protective role of COVID-19 vaccines for reducing risk of adverse health outcomes. We will use our findings to help inform maternity and child health care providers, health agencies and Canadian families about the potential long-term risks associated with COVID-19 in pregnancy, and support early screening and intervention of at-risk children to give them the best possible starts in life.",,-99,Ottawa Hospital Research Institute,128727.97,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P25839,477307,Evaluating the Feasibility of Training and Deploying Peer Champions to Support Healthcare Workers Psychosocial Needs Utilizing the STEADY Wellness Program Framework,"COVID-19 has negatively impacted the mental health of Healthcare Workers (HCWs) who are already at-risk due to their high-pressure work. Many organizations have offered reactive support, without a structured implementation approach, solid evidence-base and/or evaluation of the real-world implementation. Over the last 4 years, our team designed an evidence-informed staff wellness program, known as STEADY (Social Support, Tracking distress, Education And Discussion and communitY), guided by strategies from the fields of Knowledge Translation and Implementation Science. STEADY aims to increase resilience and mitigate negative mental health outcomes associated with workplace stress by increasing sense of social support and community at work and educating staff on mental health and coping. We successfully implemented STEADY in 10 teams in a hospital for 1-year as a quality improvement project. We found that STEADY was feasible to implement and pragmatically useful in supporting distressed HCWs and that staff wanted peer support. We adapted STEADY, based on these findings. The new Peer-Led STEADY (STEADY-P) includes training 200 HCWs as peer supporters with the skills and resources to flexibly use the STEADY-P framework to support their teams with some support in delivering programming to HCWs. The aim of this research project is to evaluate the feasibility of implementing STEADY-P across a large organization, while exploring impact on HCW who engage in programming and on organisation absenteeism data. We will measure the acceptability and impact of STEADY-P facilitator training and collect data on how the STEADY-P framework is used in practice. This will include gathering reports of the facilitator's experience, and the HCWs experience of receiving support. Data collected in this project will benefit future implementation of HCW wellness programming, while filling a key gap in this area of research.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",73103.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P25842,500548,Optimal geographic placement of integrated community health services centres: with a focus on health equity and sustainability,"Ontario's long-standing surgery wait-times issue has worsened during the COVID-19 pandemic. Establishing Integrated Community Health Services Centres (ICHSCs), which are stand-alone facilities that provide publicly funded, low-complexity day surgeries, may be a viable mitigation strategy that will alleviate pressures on the hospital and shorten surgical wait times. Recent legislation passing in Ontario (Bill 60) has demonstrated an appetite to pursue ICHSCs, but to our best knowledge, there is a gap in knowledge regarding where to place such facilities, how to structure them and their impact on patients, Canadian healthcare, and the environment. We will study these gaps using existing datasets from Ontario with a national stakeholder engagement. This study brings together seasoned healthcare leaders, physicians, patients, and other stakeholders to comprehensively assess the potential creation of ICHSCs in Ontario and nationally. Statistical analyses will be performed related to three aims: 1) identify the optimal locations for new ICHSCs; 2) measure impacts of ICHSCs on surgical care delivery (e.g., reducing wait times), population health (e.g., reducing mortality), and health equity for marginalized populations (e.g., recent immigrants and rural residents); and 3) quantify the environmental impact of ICHSCs in terms of organizational lifetime carbon footprint. We will engage national stakeholders throughout the study to devise policy recommendations that could aid ICHSC planning in Ontario and contribute to a general evaluation/decision-making framework for other jurisdictions. Findings of this study will provide actionable insights to inform patient-centred ICHSC planning that is also equitable and sustainable, to advance the well-being of the general population and those who have been historically underserved, in Ontario and beyond.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",60040.01,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25843,446147,Yves Joanette Award of Excellence in Research in Aging: Experiences of care aides in long-term care with residents having psychological trauma,"Estimates of posttraumatic stress disorder are 9.2% in the general population and as high as 22% in long-term care (LTC) homes. Residents with past trauma have more agitation and aggressive behaviours in response to triggers that may be mistaken for responsive behaviours of dementia. Care aides frequently experience the resultant responsive behaviours (e.g., being yelled at, hit), that are a significant contributor to care aide burnout. These challenges for care aides and residents have been sharply exacerbated by the pandemic. We located no studies in the literature focused on how care aides manage these residents. Therefore, we recently completed a short trauma assessment administered to over 4000 care aides. The responses revealed that care aides frequently encounter residents with traumatic histories and that they struggle to find strategies with which to assist them. Our objective is to explore the impact of residents' past and present psychological trauma on quality of worklife for frontline staff in long-term care. We will conduct interviews with care aides to understand some of the complex ways that responsive behaviours affect the quality of work life when caring those with dementia and a history of trauma. We will uncover their unique challenges and how they cope and use this information to explore what support care aides would find most valuable and how managers could assist them and ultimately contribute to improving quality of care for residents with a history of psychological trauma. The results of this study will guide intervention development to assist care aides to care for these residents. We will share our study findings with nursing homes managers and directors of care. Together, we will discuss our results and generate recommendations on how best to assist care aides working with this population to improve quality of care and life for nursing home residents with dementia and a history of past trauma.",,-99,University of Alberta,20919.33,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25845,448914,Prevention of the immunopathology induced by SARS-CoV-2,"SARS-CoV-2 infected patients develop pneumonia, which in severe cases leads to fatal respiratory failure and acute respiratory distress syndrome. Currently there are no drug therapies available for COVID-19. Respiratory syndrome severity and vascular permeability are related to local inflammation, lung damage and cell death. Coronaviruses by counteracting the host immune defense contribute in disequilibrium between inflammation and antiviral response. The loss of lymphocytes also characterizes SARS-CoV-2 infection and is linked to a worst prognosis. Thus, immunopathology is critical in determining the outcome of COVID-19 infection. Therefore, therapeutic strategies aiming at reducing inflammation and tissue injury and sustaining immune defense may reduce COVID-19 pathology. In the context of this application, we combined the expertise of virologists, molecular biologists and immunologists to evaluate the therapeutic potential of a series of compounds previously demonstrated to modulate inflammation and cell death. We will benefit from an animal respiratory Biosafety Level 3 laboratory dedicated for the manipulation of highly infectious viral material. This will offer the opportunity to analyze tissues that are of difficult access in patients, as well the impact of these compounds against SARS-CoV-2 variants. This program, in addition to generating knowledge of how these compounds prevent the pathological response to SARS-CoV-2 infection in a relevant animal model, will allow the identification of new biomarkers that may be helpful in predicting patients at higher risk to develop a fatal disease and long-term COVID-19.",,-99,Université Laval,397063.52,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P25849,448828,Evaluating the impact of resource navigators in supporting Long Term Care Home personal support workers during the COVID-19 pandemic,"More than 80% of the people who died of COVID-19 in Canada lived or worked in long term care homes (LTCH) and assisted living facilities. Almost 60% of LTCH staff are personal support workers (PSWs) who provide over 90% of direct resident care. PSWs' essential, frontline work puts them at increased risk of COVID-19 infection. Also, PSWs are an unregulated workforce who face many challenges due to systemic inequities and require access to supports and resources during the pandemic. We will use a randomized trial to evaluate the impact of providing PSWs working in LTCH with 1:1 tailored support from a resource navigator + educational resources compared to educational resources only. The primary study outcome is the impact of the intervention on PSW wellness. Secondary outcomes include burnout, knowledge of, access to and use of wellness supports, rates of COVID-19 infection and vaccinations, hospitalizations and deaths. We will also evaluate the quality of implementation of the study intervention.",,-99,Unity Health Toronto,312615.63,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health workforce",2021 +P25850,473322,"What happened and why? Exploring the development, implementation and impact of COVID-19 public health policies in Ontario using a health equity lens","Communities who experience social and economic inequities were hardest hit by the COVID-19 pandemic. One-size-fits-all public health policies (PHPs) do not sufficiently address inequities. It is essential that PHPs be developed and implemented with health equity in mind. As we prepare for a post-pandemic recovery and for future health emergencies, it is important for us to look back and assess how and why PHPs were developed and implemented in Ontario. In Objective 1 of the study, we will answer ""what happened"" by categorizing all PHPs pertaining to vaccinations and isolation supports in Ontario and querying whether and how they considered health equity. In Objective 2 of the study, we will determine ""why"" public health policies were developed or implemented using (or not using) a health equity lens. In Objective 3, we will determine ""what we could have done differently"" by using mathematical models to compare the potential impacts of different PHP combinations. In Objective 4, we will learn ""what it would take to do things differently"" by asking public health actors to describe the barriers and enablers to developing and implementing PHPs that prioritize the needs of those most at-risk of infection and negative health outcomes. Our team includes government and public health decision makers from the federal, provincial, and local/regional levels. Our team also includes representatives of health-equity focused organizations, who supported implementation of public health policies at the provincial and local/regional levels.",,-99,Unity Health Toronto,76662.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in the Allocation of Resources | Policy research and interventions,2022 +P25851,498866,Impact of intestinal dysbiosis and microbiota-derived extracellular vesicles on the pathogenesis and clinical manifestations of long COVID,N/A,,-99,Institut de recherches cliniques de Montréal,18389.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P25852,489798,Impact of intestinal dysbiosis and microbiota-derived extracellular vesicles on the pathogenesis and clinical manifestations of long COVID,"It is estimated that 14.8% of Canadians who had COVID-19 will have complications lasting beyond 12 weeks after the initial infection (i.e., long COVID). Long COVID can be debilitating and last for years. Some of the most common and long-lasting symptoms are neuropsychological and include extreme fatigue, brain fog, and symptoms of depression and/or anxiety. The causes of long COVID are poorly understood, and as a result, diagnostic blood tests and effective treatments are lacking. Our previous studies suggest that long COVID is associated with a disruption of the intestinal microbiota (i.e., community of bacteria that live in the gut) which causes leaky gut and inflammation. We hypothesize that these perturbations of the microbiota contribute to the development and persistence of the neuropsychological manifestations of long COVID. However, the mechanisms by which changes in the intestinal microbiota can cause these neuropsychological complications are unknown. Bacteria have been shown to shed parts of themselves in the form of circular structures that pinch off like knobs of dough called extracellular vesicles (EVs). EVs contain several molecules that can have an impact on different cells in the body. Given that the microbiota is mostly composed of bacteria, we believe that microbiota-derived EVs can cause inflammation in the gut leading to leakiness which allows for microbiota-derived EVs to transfer from the gut into the bloodstream thereby causing inflammation in the brain. We will test this hypothesis using mice that have been exposed to stool or microbiota-derived EVs from patients with and without long COVID. We will also evaluate the impact of microbiota-derived EVs isolated from the blood and stool of patients with long COVID on human gut, blood and neural cells. We expect that these studies will help us identify new ways to diagnose and possibly treat long COVID by targeting the gut microbiota and microbiota-derived EVs.",,-99,Institut de recherches cliniques de Montréal,762492.52,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P25853,463759,Formulation optimization and characterization of a novel combination adjuvant for pandemic preparedness,"Novel adjuvants for vaccines are highly desirable, especially if they can be synthesized instead of being derived from natural products. Additionally, the adjuvant should be capable of inducing a greater and more desired immune response - such as directing the response towards a Th1-like response. TriAdj is a fully synthetic adjuvant that directs the immune response towards a Th1-like response and moreover, is capable of providing protection in both the upper and lower respiratory tract in multiple animal models of multiple pathogens. TriAdj has proven effective in ferret, hamster and African green monkey models of SARS-CoV-2 and an alpaca model of MERS-CoV. It will be used in a phase 1 clinical trial starting in fall 2021. Here we propose to optimize the order and state in which the 4 components a TriAdj containing vaccine are assembled to move the development of TriAdj, to a higher level of tech readiness. TriAdj is a three component adjuvant that when mixed with an antigen, in this case the S1 protein from SARS-CoV-2 for an antigen/adjuvant complex that is more effective at inducing an immune response than when it is not in this complex. Our current formulation requires three individual vials, which is not optimal and therefore we will determine whether and how best to formulate this vaccine so that it can be used in a conventional two or single vial manner. To do this, we will assess various orders of addition and state (liquid/dry) to streamline this product. To characterize the structure of the adjuvant/antigen complex we will also perform state of the art imaging, which will help link the structural characterization of the vaccine to its performance. Further development of TriAdj will provide a tool to be used against emerging Disease X-like pathogens.",,-99,University of Saskatchewan,157229.52,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine design and administration,2021 +P25854,422763,Animal models for SARS-CoV-2: vaccines and immune enhancement,"In December 2019 a novel coronavirus (CoV) was identified as the cause of pneumonia in a cluster of patients in Wuhan, China. This virus is related to severe acute respiratory syndrome (SARS)-CoV and has been named SARS-CoV-2. In less than two months, there have been over 69,000 cases and over 1600 deaths. Quarantine measures have been imposed on entire cities in China in an attempt to control spread. Cases of SARS-CoV-2 have been identified in 28 other countries and there is concern that this could lead to global pandemic. Here we propose to identify what common lab and agricultural animals may be infected with SARS-CoV-2. This addresses two important questions. What animals can be infected and may pose a risk (or are at risk) and can these animals be used to models. Animal model allow us to understand how the virus causes disease, whether vaccines can be developed that protect from disease and how might the virus be transmitted. These are critical questions that need to be addressed when a new pathogen emerges. In addition, there is some concern that less than optimal vaccines or previous exposure to related pathogens could exaserbate disease - this is a somewhat unique phenomenom that was observed with SARS-CoV vaccines. We plan to investigate whether these animal models can be used to test for this, to ensure that vaccines are safe prior to testing in human clinical trials.",,-99,University of Saskatchewan,758148.28,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Disease models | Pathogen morphology, shedding & natural history",2020 +P25861,446742,Ontario SPOR SUPPORT Unit: Ontario's Catalyst for Patient-Oriented Research,"Health research is key to improving the lives of Ontarians. Health research can lead to better health, better health care experience, and better ways to provide health care to everyone. At OSSU, we make sure health researchers in Ontario effectively work with patients, families and caregivers. This partnership can ensure health research meets the needs of people in Ontario. OSSU enlists the best research teams throughout Ontario and they help health research to benefit the people of Ontario. Research with and for everyone OSSU works to make sure health research can partner with anyone, including people that are often left out. This means we support First Nations' research, address racism and sexism in research, and support French-language research. We make sure the results of research reach all who could benefit not just certain groups. Improving health care OSSU links patient-partnered research with what the health system most needs by working closely with Ontario's Ministry of Health and people working in the provincial health system. One way OSSU does this is to be the hub for patient-partnered research that can help different parts of the health system (like hospitals, health teams, family doctors and others). We help these groups learn what works and what doesn't in providing health care of the people of Ontario. For example, due to the COVID-19 pandemic, most people have to visit their doctor over the phone or via a computer not in person. Our patient-partnered research will find out what it takes to make this type of 'virtual visit' work for people in Ontario, without leaving out people who would much prefer to see their doctor in person. Making an impact At OSSU we will apply the knowledge gained from Ontario's patient-partnered research to make a difference for everyone in Ontario.",,-99,Ottawa Hospital Research Institute,25957039.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Policies for public health, disease control & community resilience | Health Systems Research",Research to inform ethical issues related to Public Health Measures | Health service delivery,2020 +P25871,476657,"Social isolation and cognitive decline in long-term care: A longitudinal, administrative data study","Since the beginning of the COVID-19 pandemic, long-term care homes across Canada have been operating under varying degrees of lockdown or restriction. These public health restrictions have put drastic limitations on residents' social interactions, including restricting visitors and volunteers from entering homes, reducing or cancelling home activities, restricting group dining, and at times requiring residents to isolate in their rooms for days to weeks. Media reports suggest that ongoing social isolation and loneliness in long-term care homes has had a devastating impact on the memory and thinking skills of long-term care residents. In this study I will: 1) describe the social isolation experienced by long-term care residents in Ontario before and during the pandemic; 2) identify and explore different patterns of resident memory and thinking decline before and during the pandemic, and; 3) evaluate if social isolation and loneliness is associated with declines in memory and thinking among residents of long-term care. This evidence will be used to help establish effective policies and practices that support resident health and well-being.",,-99,Bruyère Research Institute,32896.55,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2022 +P25874,443331,COVID-19 Variant Network - Understanding the pathogenesis of COVID-19,"Pulmonary infections by viruses such virulent Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) and Middle East Respiratory Syndrome (MeRS) CoV associated with significant morbidity and mortality. Clinically, infections by these viruses are associated with a pronounced lung inflammation, causing respiratory problems that often develop in secondary pneumonia. Inflammation is the result of immune activation in response to infection. When activation is too pronounced or sustained for extended periods of time, complications occur. Two main mediators of inflammation are known: Cytokines and lipid mediators of inflammation (LMI). In the current proposal we will study the inflammatory response during infection/exposure of lung and blood cells to the newly described COVID-19 and compare this response to that of SARS-CoV-2 and MeRS-CoV to obtain correlates of pathogenicity between these viruses. We will use primary lung cells and white blood cells from donors to conduct our studies. The mediators of inflammation will be identified and quantitated using state of the art methodology available in our laboratories. More than 200 LMI and 150 cytokine/cytokine receptors will be examined. Upon completion of this proposal, a detailed analysis of the response of primary epithelial cells and leukocytes to COVID-19 will be obtained, enabling the rational design of therapeutic strategies to help combat COVID-19.",,-99,CHU de Québec,78392.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2021 +P25876,486341,Understanding the Role of Immunoglobulin A in Respiratory Virus Infection,"Effective immunity against respiratory viruses is facilitated by mucosal immunity, which relies, in part, on the action of immunoglobulin A (IgA). Little is known about the mechanisms through which IgA mediates protection against respiratory virus infection. Indeed, the effect of subclasses (IgA1 and IgA2), relative contributions of neutralization vs. Fc-mediated effector functions, and antibody structures (monomeric, dimeric, secretory) on protection against SARS-CoV-2 and influenza A virus (IAV) infections has so far been elusive. The overarching aim of this research is to systematically define how the aforementioned features of IgA impact its ability to protect against IAV and SARS-CoV-2 infection. We hypothesize that the interaction between IgA and the Fc alpha receptor plays a vital role in the maintenance of immunity against these respiratory viruses. The first aim of research is to characterize how IgA subclass (IgA1 vs. IgA2) affects binding and neutralization properties. A variety of anti-hemagglutinin (HA) monoclonal antibodies against IAV, and anti-S protein monoclonal antibodies against SARS-CoV-2 will be cloned, expressed, and purified. Each will be produced in monomeric, dimeric, and secretory forms, and binding kinetics will be measured by ELISA and biolayer interferometry assays. Neutralization assays will also be performed using live viruses. The second aim of research is to determine the impact of IgA subclass and structure on the ability to activate neutrophils via the Fc alpha receptor. Virus-IgA complexes will be incubated with neutrophils to measure their activation. Finally, the third aim of research is to determine how IgA subclass and structure influence efficacy in vivo using transgenic mice expressing the human Fc alpha receptor.",,-99,McMaster University,13021.09,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P25877,486342,Face masks during exercise: Investigating sex differences in the multidimensional components of dyspnoea,"To contain the SARS-CoV-2 virus, public health officials have implemented face mask (FM) mandates. Initially, many researchers feared that individuals who exercise with a FM would be faced with a respiratory resistance that could reduce oxygen and increase carbon dioxide levels in the blood. However, recent studies show no adverse physiological effects when a healthy individual exercises with a FM. Despite this observation, studies consistently demonstrate that FMs increase the sensation of breathlessness. Unfortunately, there are few studies explaining the causes of breathlessness with a FM. Moreover, it is unknown if biological sex influences the experience of breathlessness with FMs during exercise. As a result, the purpose of our study is to examine the mechanisms of breathlessness with FMs in males and females during exercise. We hypothesize that females will experience more breathlessness with FMs, which will be due to their relatively higher levels of breathing resistance and increased levels of respiratory muscle electrical activity with FMs compared with males. In our study, males and females will undergo two aerobic exercises tests. In randomized order, the participants will complete the tests with and without a mask while we measure the multiple components associated with breathlessness and various physiological outcome measures. Our research will be the first to provide detailed insight into the effects that FMs pose on males and females, and will provide essential data needed make recommendations for FM use.",,-99,University of British Columbia,13021.09,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2022 +P25880,459289,COvid-19 Vaccines Booster in Immunocompromised Rheumatic Diseases (COVBIRD).,"In the midst of a fourth wave and the circulation of the delta variant, Quebec and Ontario offer a third dose of mRNA COVID-19 vaccine to immunosuppressed patients including people living with systemic autoimmune rheumatic diseases (SARD). However, the safety and the response to a third dose of vaccine in rheumatic disease patients is unknown. Moreover, initial results from an ongoing study demonstrated that SARD patients treated with rituximab, a drug that depletes cells producing antibodies, have a poor response to two doses of an mRNA vaccine. Since this group is also less likely to respond to a third vaccine dose, defining strategies to enhance responses to COVID-19 vaccines in these vulnerable patients is a priority. Hypothesis: A fourth dose of a non-mRNA vaccine, in SARD patients treated with Rituximab who do not respond to a third dose, is safe and enhances the number of patients who develop post-vaccine antibody responses. Primary Aims: To evaluate the safety of a 4th dose of vaccine in SARD patients treated with rituximab and the vaccine induced antibody responses. Secondary Aims: To compare the response following a 4th dose of a non-mRNA vaccine; to evaluate the effect of immunosuppressive treatment on the response post-4th dose; to compare the rates of disease flares post-4th dose of a non-mRNA vaccine; to assess the persistence of humoral responses induced by a 4th dose of a non-mRNA vaccines. Design: This multicenter clinical trial will enroll SARD patients on rituximab who did not respond to a third dose of a COVID-19 vaccine. These patients will be offered a 4th dose of non-mRNA COVID-19 vaccines that will be approved in the coming months by Health Canada. Significance: This study is key to inform public health authorities on the advantage of using specific vaccine types to achieve satisfactory vaccination in the most vulnerable SARD patients.",,-99,Université Laval,784891,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Characterisation of vaccine-induced immunity | Adverse events associated with immunization,2021 +P25882,494292,Development and Commercialization of a Safe and Effective Mpox Subunit Vaccine with Global Impact,"In a rapidly changing global landscape characterized by expanding human populations, diminishing habitats, and evolving disease patterns influenced by climate change, the likelihood of zoonotic diseases transitioning to humans has escalated. The recent COVID-19 pandemic underscored our unpreparedness, leading to significant health and economic impacts. While rapid solutions such as first-generation mRNA vaccines were developed, their payload capacity may not suffice to counter novel threats from Orthopoxviruses like monkeypox (Mpox). Concurrently, existing attenuated vaccines for poxviruses can be ineffective and, at times, induce adverse side effects, particularly in immunocompromised individuals. Here we propose to use innovative vaccine platforms to develop a safer and more effective Mpox vaccine than what is currently available by creating a subunit vaccine that retains a large number of immunologically important targets while removing the toxic side effects. In collaboration with Eyam Vaccines and Immunotherapeutics Ltd., we aim to create the first Mpox vaccine crafted by Canadian scientists and manufactured and distributed globally. This breakthrough will not only help protect vulnerable populations but also establish a rapid vaccine response system for other emerging pandemics caused by zoonotic diseases. Finally, the past pandemic has provided profounds evidence that Canada should be in control of its own vaccine supplies and this proposal will facilitate this goal.",,-99,University of British Columbia,73558.84,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",Canada,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine trial design and infrastructure,2023 +P25883,462610,Establishing Feasibility & Safety of Providing Critical Care Treatments for Patients with Ebola in a Simulated Ebola Treatment Centre: Phase 2,"Historically, approximately 70% of people in Africa infected with Ebola virus have died. Most commonly, people develop vomiting and diarrhea, become severely dehydrated, their blood pressure falls, and their vital organs fail. If we can support patients until they receive specific treatments and produce antibodies to clear the virus from their system, mortality in Africa falls to about 40%. Governments and humanitarian organizations did not believe it was possible to deliver such care in the West African outbreak; however, one Ebola treatment center in West Africa demonstrated it was possible to provide critical care, including life-sustaining support for the heart, lungs and kidneys. Among patients evacuated to European and US hospitals with advanced critical care, just 20% of patients die. We have built a simulated treatment centre in Canada to ""practice"" the provision of advanced care to patients, demonstrating to others that we can deliver excellent care to help patients survive. Our Canadian treatment unit is a collaboration with the Canadian Forces, humanitarian aid organizations, African colleagues and the WHO. It simulates the temperature & humidity of West Africa, and with medical mannequins, we are testing the feasibility and safety for health workers in wearing protective medical equipment while providing resuscitation, mechanical ventilation and dialysis. This treatment unit and procedures will serve as an example to health teams - humanitarian organizations, African and Canadian - about what is possible. Our team has experience treating Ebola patients, building treatment centers in Africa, training health workers, and with support from CIHR have completed preparatory testing. We are ready to begin the next phase of this research. By involving trainees and engaging partners from Africa and Canada throughout the process, we are poised to influence Ebola care around the world.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",193867.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Clinical,Not applicable,Filoviridae,,,,,,,,,Ebola virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P25884,484194,Surveillance of Healthcare and Ambient Pathogens in our Environments and Spaces [SHAPES],"As an alternative to the time-consuming and resource-intensive process of testing individual humans, our team's previous work looked at how we can use environmental sampling to predict and potentially prevent COVID-19 outbreaks. The approach we developed uses swab samples taken from floors, which then undergo a lab processing technique that can detect the presence of the SARS-CoV-2, the virus that causes COVID-19. Through our work, we have discovered that the amount of SARS-CoV-2 we find on the floor correlates to the burden of infection in individual humans living and working in a given setting, and that the virus can be detected from floor samples days before an outbreak is recognized. This suggests a potential role for floor sampling in improving early outbreak identification and monitoring. We have further developed our approach to allow us to detect up to four different respiratory pathogens in one single test: SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV). Our proposed work aims to provide ongoing surveillance at 10 long-term care homes for one year. We will conduct floor swabbing for SARS-CoV-2, influenza A and B, and RSV, and will send reports to each home on a twice-weekly basis. These reports will indicate the number of swabs positive for SARS-CoV-2, the location where the swab was taken, and the trends in swab positivity over time. We will look at the number and duration of outbreaks in homes who received swabbing and reporting compared with other homes who were not swabbed. We will look at whether the RSV and flu virus we find on the floors correlates to infection in LTC residents. We will also look at how floor swabbing compares to the current process of twice-weekly rapid antigen testing for LTC staff. We hope to lay the groundwork for routine environmental surveillance of these common and potentially dangerous viruses, especially in settings where there are vulnerable people.",,-99,Lunenfeld-Tanenbaum Research Institute (Toronto),73535.55,Human Populations | Environment,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical | Non-Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2023 +P25885,473338,Surveillance of Healthcare and Ambient Pathogens in our Environments and Spaces [SHAPES],"As an alternative to the time-consuming and resource-intensive process of testing individual humans, our team's previous work looked at how we can use environmental sampling to predict and potentially prevent COVID-19 outbreaks. The novel approach we developed uses swab samples taken from floors, which then undergo a lab processing technique that can detect the presence of the virus. The SHAPES project looks at expanding this approach beyond COVID-19 to other common infectious diseases in vulnerable populations. Our proposed work aims to assess the already-collected swab samples for two additional respiratory viruses (influenza and RSV) and two bacteria (VRE and C. difficile), which will allow us to quantify the prevalence of these organisms. In the second part of the work, we will collect additional swab samples to determine how detection of these pathogens correlates to infections in humans at the sampling location. Our goal is to see what these floor samples can tell us about [1] whether a pathogen is present in an environment and [2] how that presence is associated with infections or outbreaks in the people in that environment. The approach of using environmental surveillance to predict and prevent outbreaks of infectious pathogens represents a new way of thinking about infection prevention. We hope to lay the groundwork for routine environmental surveillance of these common and potentially dangerous viruses and bacteria, especially in settings where there are vulnerable people, like long-term care homes and hospitals.",,-99,Lunenfeld-Tanenbaum Research Institute (Toronto),76662.06,Human Populations | Environment,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease surveillance & mapping,2022 +P25888,454196,Outcomes of pregnant women and infants with SARS-CoV-2 vaccine and infection exposure,"Emerging infectious disease events, such as the current global SARS-CoV-2 pandemic, are often associated with disproportionately negative health outcomes for pregnant women and infants. Significant delays in implementation and reporting of robust research findings on SARS-CoV-2 vaccine safety and efficacy, as well as infection outcomes, has led to considerable vaccine hesitancy in the vulnerable pregnant population. Primarily, this research project will use extensive demographic, epidemiological, and clinical data from an established large prospective cohort study (the P3 cohort study) on 4000 pregnant women and their infants in Alberta, Canada, with follow-up continuing until 1 year postpartum. A sub-study on vaccine willingness and perceptions will also be done. Analysis of this data will provide accurate estimates of the risk of various health outcomes (e.g. pregnancy complications, neonatal complications) following SARS-CoV-2 infection in pregnant women and infants. It will give vital information on the real-world safety and efficacy of vaccination in a representative Canadian population, along with key insights into the necessity and timing of 'booster' shots. Secondarily, electronic medical record (EMR) data for participants will be compared to similar data from the prospective P3 cohort study. A validation will be done of the EMR data to see if it can be used in the future for rapidly implementing robust research on emerging infections in pregnancy. In areas (i.e. certain data types) where EMR is not valid, statistical approaches will be trialed to facilitate optimal use of this information for pandemic preparedness. The results of this study will be shared with other researchers as well as with the public through internal (University of Calgary), regional (SARS-CoV-2 and perinatal epidemiology networks within Alberta and Canada), and international (World Health Organization) collaborations. This research will be completed over a period of two years.",,-99,University of Calgary,110402.31,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P25894,430185,Implementation of public health measures for vulnerable populations during the COVID-19 pandemic in French-speaking African countries in conflict: Case study in Mali and Burkina Faso,"The first case of COVID-19 in Africa was confirmed on 14 February 2020, and within weeks the virus had spread to every country. The impact of the COVID-19 pandemic could be devastating in African countries, especially those weakened by conflict, which host thousands of refugees, internally displaced persons (IDPs), and migrants. In the absence of treatments or vaccines, governments and humanitarian actors have implemented public health measures to slow the spread of the virus. In Mali and Burkina Faso, these measures include isolating COVID-19 patients and quarantining suspected cases at home. Social distancing and lockdown measures are also being implemented to mitigate the pandemic. For IDPs and migrants, implementing these measures is more difficult due to the crowded and unhygienic conditions in which they live. In addition, many people are unaware of the existence of these guidelines, do not understand them, or are not convinced of their importance. This research will help to better understand the challenges faced by authorities and humanitarian actors in implementing public health measures in response to COVID-19, as well as the difficulties faced by IDPs and migrants in adopting these measures. It will examine the relevance of each measure to the specific context in which IDPs and migrants live and propose appropriate adjustments. Our findings will help to identify best practices and provide assistance tailored to the needs of IDPs and migrants so that they can better implement social distancing and containment measures. Our findings may contribute to increasing the adaptation of public health measures in other contexts, in order to slow down epidemics in general.",,-99,Université Laval,79306.74,Human Populations,Asian,Unspecified,Unspecified,Internally Displaced and Migrants,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +P25895,425043,"Digital interventions to detect, prevent and manage mental health problems in people with chronic diseases: Knowledge synthesis","The global COVID-19 pandemic is affecting most countries and has caused hundreds of thousands of deaths to date. Considered a humanitarian disaster, it will have serious impacts on the mental health of the population, especially the most vulnerable groups, including people with chronic diseases. These individuals are at greater risk of developing mental health problems such as anxiety and depression, risks increased by the loss of social support and loneliness. If left untreated, these problems can have long-term consequences on people's health and increase the costs related to their treatment. Scientific studies have demonstrated the effectiveness of front-line interventions to improve the management of mental health problems in people living with chronic diseases. However, there is little knowledge about interventions that use digital technologies. In the context of the current crisis, these technologies can be a relevant solution to better reach people living with chronic diseases and intervene with them. Our project will verify whether there are effective digital health interventions to prevent, detect and manage mental health problems in people living with chronic diseases. First, we will consult documents that summarize the results of research on the subject. Then, we will summarize the knowledge identified and share it with the team's partners. Finally, we will conduct further research in the scientific literature in order to most adequately answer the partners' questions. This project will make it possible to develop digital health solutions for optimal monitoring of mental health problems in people with chronic diseases, adapting to the context of the COVID-19 crisis.",,-99,Université Laval,35562.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25897,458917,"Longitudinal Cohort Analysis of Antibody Responses Neutralization Efficiency and Long-Term Immunity in natural SARS-CoV-2 infection, Vaccination and its robustness against emerging Variants of Concern.","The pandemic of SARS-CoV-2 and it's associated disease (COVID-19) has resulted in millions of deaths and deep socioeconomical impact globally. While countries such as Canada are trying to reach a level of vaccine acquired herd immunity many questions remains on SARS-CoV-2 immunity. To answer those questions, 1,000 individuals from the Ottawa/Gatineau region have been recruited and enrolled in a longitudinal cohort study called Stop the Spread Ottawa https://omc.ohri.ca/SSO/ (SSO) for an initial period of 10 months. During this period, saliva samples have been collected to access the presence of the virus as well as monthly blood draw to test the presence of antibodies using our established high-throughput robotic testing lab. A second phase of SSO will continue to track a subset (n=300) for an additional 34 months making SSO one of the largest and longest study of SARS-CoV-2 immunity in Canada. The samples collected within this study are of extreme value due to the fact that contain baseline samples acquired before SARS-CoV-2 infection and most importantly before Vaccination. These rare samples therefore holds precious research opportunities. Some of the question we aim to answer are the following : How long does immunity last after natural infection and vaccination? Are some groups of participants mount less robust immune responses following vaccination which can lead to breakthrough infection? How does natural infection and vaccination protects against emerging variants (VOC)? Is a vaccine strategy more robust and long lasting than others? Furthermore, using this cohort, post-infection sequelae (I.e. long COVID-19, post-COVID syndrome) and the impact of auto-antibodies will be investigated. Critical information about antibody-mediated immunity will be shared with the scientific community and local/regional/national health authorities which will guide public health measures, vaccination strategy (need for booster) and VOC impact in Canada.",,-99,University of Ottawa,84625.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P25900,467743,Sexual and mental health of Black queer communities during the COVID-19 pandemic,"COVID-19 has had a large impact on the health and well-being of all people. However, some groups have been impacted more than others. African, Caribbean, and Black people, as well as, two-spirit, lesbian, gay, bisexual, transgender, queer and other gender and sexual diverse people (2SLGBTQ+) have been especially hit hard by COVID-19. This research study wants to understand the experiences of Black 2SLGBTQ+ who live in Ontario during COVID-19. We are especially interested in how Black 2SLGBTQ+ people accessed sexual health resources (HIV testing, PrEP, sex education) and mental health services (peer counselling, therapists, social worker). We want to know how Black 2SLGBTQ+ have survived and thrived during this difficult time. We will invite 64 Black 2SLGBTQ+ people to participate in community discussions to talk about their experiences during COVID19. The discussions will take about 1.5-2 hours and participants will be compensated for their time. We hope that the information shared by participants will help us develop community develop resources and services for Black 2SLGBTQ+ people in Ontario.",,-99,"Ontario Institute for Studies in Education (Toronto, Ontario)",69940.06,Human Populations,Black,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25902,494284,"Development of RNA therapies against SARS-CoV-2, other coronaviruses and influenza viruses for pandemic preparedness","Despite the availability of effective vaccines and some treatment options, SARS-CoV-2 (CoV2) -the causative agent of the COVID-19 pandemic - and its variants continue to circulate. Due to the limitations of current treatments (contraindications and rebounds after treatment interruption for Paxlovid; intravenous injections for monoclonal antibodies), effective and simpler to use antiviral medications are still needed to help reduce the morbidity and mortality from the ongoing pandemic. Other coronaviruses and influenza viruses will certainly emerge in the future and they have a pandemic potential. To decrease the risks that we faced with the COVID-19, a work-flow to rapidly respond to them would be extremely helpful. RNA therapies represent a promising strategy to quickly target these viruses. In response to the COVID19 pandemic, our groups have developed small therapeutic RNAs specific against CoV2 and a group of small RNAs that enhance innate immune responses against coronaviruses and influenza viruses. We will further develop them to bring them to clinical trials so that they can be used by intra-nasal delivery. Based on those, we will develop a work-flow to quickly synthesize antiviral RNA therapeutics and test them against these two families of viruses to be ready once a new viral pandemic with a respiratory virus emerges.",,-99,Lady Davis Institute for Medical Research (Mtl),73558.84,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P25903,475699,Evaluating the real-world impact of Internet-delivered Cognitive Behavioural Therapy (iCBT) through the lens of the RE-AIM framework: a retrospective cohort study in Ontario,"Mental health (MH) disorders are common, affecting up to one in five Canadians each year, and causing substantial disability and economic burden. Yet many do not receive sufficient MH services to meet their needs. Given these growing demands, in 2020, Ontario launched Internet-delivered Cognitive Behavioural Therapy (iCBT), a short series of online modules that were shown to be effective tor treating anxiety and depression when investigated in randomized controlled trials. However, the real-world impact of iCBT when implemented in routine care is unknown. To address this gap, in my dissertation, I will: (1) describe the characteristics of individuals receiving iCBT in routine care; (2) examine patient outcomes, including depression and anxiety symptom reductions and health service use (e.g., visits to doctors, emergency departments, and hospitalizations) before and after the intervention; and (3) quantify health-system costs. In doing so, my study will assess whether iCBT reaches those in need of MH services and how it impacts both patient- and health-system outcomes. With the COVID-19 pandemic reinforcing the urgency for developing virtual MH supports, this research will inform the wide-scale implementation of iCBT to ensure that this promising intervention improves the delivery of MH services in the province and beyond.",,-99,University of Toronto,77083.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25906,476136,Development and performance testing an agnostic next-generation sequencing assay for detection of respiratory RNA viruses from clinical samples,"The COVID-19 pandemic has emphasized the need for rapid, comprehensive, and user-friendly diagnostic testing strategies. Metagenomic sequencing - non-specifically sequencing all of the nucleic acid within a sample - offers researchers the opportunity to agnostically detect pathogens from clinical samples. Previous work, including work towards my PhD thesis, has demonstrated the feasibility and utility of metagenomic sequencing for the detection and characterization of RNA viruses. However, several barriers still exist that prevent the widespread translation of metagenomic sequencing methods to diagnostic laboratories including, lengthy end-to-end assay completion times, lack of automated laboratory protocols, and poor diagnostic sensitivity for weakly-positive specimens. My proposed PhD research aims to address these barriers. I will optimize and validate a metagenomic sequencing assay; my approach will include combining RNA to cDNA synthesis, amplification, and sequencing library preparation in one-step. I will also include a new method to deplete human cDNA to concentrate on sequencing of viral targets and improve diagnostic sensitivity. I will test this method on SARS-CoV-2 samples, followed by quantification of diagnostic test performance using contrived samples containing other respiratory RNA viruses (influenza A/B, respiratory syncytial virus). Finally, clinical validation of our assay will be performed using inpatient and outpatient samples collected during the 2023 respiratory virus season. This project is supported by the U.S. Biomedical Advanced Research and Development Authority, and is embedded in the BC Public Health Laboratory, ensuring that the metagenomic sequencing assay can be tested, approved, translated, and implemented in clinical and surveillance settings.",,-99,University of British Columbia,77083.46,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2022 +P25907,448025,"RÉAC! Responsiveness of newcomer care to the COVID-19 pandemic in Montreal, Sherbrooke and Toronto: a participatory mixed research project","Migrant populations are among the groups most likely to have poor health. In Canada, institutional management of the health and social services needs of these populations is complemented by the action of community organizations. In Quebec and Ontario, these organizations intervene in several sectors: psychosocial support, housing, food security, and job search. COVID-19 has disrupted the ways in which these organizations operate, forcing them to adopt new ways of serving their beneficiaries in order to comply with the measures in place. This research is taking place in Montreal, Sherbrooke and Toronto, in the two leading migrant-receiving provinces in Canada - and which are the most affected by COVID-19. Our study integrates community stakeholders as well as policy makers and managers of health and social services networks (HSSNs) into the research process. It concerns the actions implemented by them in the context of the pandemic. Three objectives are targeted: 1) to shed light on the innovations that emerge from the adaptation of community organization and RSSS services, 2) to study the needs of beneficiaries, 3) to support the integration of promising innovations that promote intersectoral collaboration (community-RSSS). To achieve these objectives, we will conduct interviews with managers and stakeholders, and surveys and focus groups with beneficiaries. The involvement of different partners, including beneficiaries themselves, gives this research a significant social impact. The lessons learned from promising innovations are indeed likely to improve care beyond the context of the pandemic: decision-makers would benefit from relying more on this experience to offer adapted, solidly funded and culturally sensitive care.",,-99,Université de Montréal,293944.58,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2021 +P25913,450572,Open Air School: Effectiveness of an intervention program involving nature to mitigate the impacts of school disruptions linked to Covid-19 on the mental health and healthy lifestyle habits of children from disadvantaged backgrounds.,"How can we reduce the consequences of the COVID-19 pandemic on the mental health of disadvantaged children, who have been hardest hit? We offer Open Air School, an outdoor education intervention involving contact with nature. There is currently a craze for outdoor education in schools, particularly since the pandemic. Could such practices have salutogenic effects? Experimental studies carried out around the world show that contact with nature (urban park or forest) improves mental health. Preliminary results seem to indicate that this is also the case for children who are in contact with nature during outdoor learning situations. However, no experimental studies have tested the effectiveness of outdoor education as a strategy for improving children's mental health. We will conduct a cluster randomized controlled trial to test the effectiveness of the Open School program. This is a nature-based mental health promotion intervention implemented by teachers. The intervention will last 15 weeks, two hours per week. We will recruit 80 schools with 5th year primary classes from disadvantaged neighborhoods, among schools which are already participating in a larger study carried out by the Observatory for Children's Education and Health (OPES). The intervention will include mental health promotion activities in nature (e.g. cooperation, compassion/empathy, mindfulness) and educational activities. We will evaluate the impact of the intervention on children's health. The results could help decision-makers implement an outdoor education program promoting mental health, based on empirical evidence, and having a high potential for deployment at the population level, at low cost.",,-99,McGill University,121279.76,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25915,448909,The Canadian Respiratory Research Network Long COVID-19 Study,"The New York Times suggested that lingering symptoms from COVID-19 may turn out to be one of the largest mass disabling events in modern history. There are almost a million Canadians infected with COVID-19 at the time of writing. Even a small amount of lung disease could have enormous health and economic consequences. Preliminary studies suggest that COVID-19 causes long-term lung damage, even in young, otherwise healthy people who did not need to go to hospital or the ICU. In recent months, new COVID-19 variants - of which little is known - have become more common and it is not known how they will affect the long-term health of people's lungs. We are a group of respiratory researchers, patients, health care workers, non-profit groups and others who want to know how common long-term lung damage after COVID-19 is, who is most affected by it and what the effects of this damage are on other important aspects of people's lives. We plan to study a large sample of people with COVID-19 from across Canada-some who needed hospitalization but most who did not. Through telephone questionnaires, we will determine their respiratory symptoms, quality of life and medical history. Then we will invite them to one of our eight Canadian testing centres to have special, thorough breathing tests. The information we learn about the effect of COVID-19 on the lungs will help patients and health care providers manage it better. It will also reveal how different COVID-19 variants affect the lungs. We will use this new knowledge to write a formal guide on what respiratory monitoring and testing should be done after COVID-19 infection. This will ensure that people affected by COVID-19 get the care they need to maintain their lung health. This will also help prevent unnecessary testing which places extra strain on the health care system and delay care for other patients.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",397222.41,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25916,443297,COVID-19 Variant Supplement - CovidFree@Home: Development and validation of a multivariable prediction model of deterioration in patients diagnosed with COVID-19 who are managing at home,"Millions of Canadians are anticipated to be infected with COVID-19 during this pandemic and many more will contract it in ongoing community transmission and/or a possible second wave. The majority of people who test positive for COVID-19 are sent home to isolate. In this population, deterioration of their disease can happen quickly and without warning, and we currently cannot accurately predict the approximately 20% who deteriorate and need hospitalization. From discussions with our patients and patient advisor, we know that people who are isolating at home feel terrified and alone. We need an effective and safe ambulatory care and research strategy for people with COVID-19 isolating at home. We are a team of heath care workers, patients, researchers and computer scientists (WearCOPD.ca; Can-BREATHE.ca) with five years of experience developing and using remote monitoring systems for respiratory disease. We have already built a smartphone application to facilitate the care of people with COVID-19 at home by allowing them to report their symptoms to their physician. With this project, we will expand our system to also include continuous smartwatch-based monitoring of heart rate, respiratory rate, cough, speech and other parameters. Sensor data will provide us with large volumes of objective data and allow us to build accurate real time machine learning models for predicting who needs to go to hospital. We will integrate these models into a dashboard that alerts clinicians of any patients that area getting worse, so that they can be called into hospital. Patients can be reassured that they are being followed thoroughly even though they are at home. Our system will also provide a platform for further research into how to prevent long term sequalae and preserve the health of people with COVID-19 who do not require hospitalization.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",39196.27,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P25917,450401,The Canadian Respiratory Research Network Long COVID-19 Study,"COVID-19 is a deadly and infectious lung disease that has infected almost a million Canadians, approximately 93% of whom recovered without need for hospitalization. Preliminary studies suggest that COVID causes long term lung damage, even in young, otherwise healthy people who did not require hospitalization. Post-acute sequelae of COVID-19 (PASC) is a new disease that is diagnosed when someone has persistent symptoms that persist beyond 12 weeks that cannot be attributed to an alternate diagnosis. We are a group of respiratory researchers, patients, health care workers, non-profits and others who want to gain a better understand of lung PASC. We want to learn how often it occurs, who gets it, what kind of damage is in the lungs, if it resolves and, if so, how quickly, and why are some people affected and others not. We plan to study a large national representative sample of people with COVID-19-some who needed hospitalization but most who did not. Through telephone questionnaires, we will determine how many have long term sequelae of COVID-19 at six months. Then we will invite random patients with and without lung PASC to one of our Canadian testing centres where we will compare the results of detailed breathings tests, 3 dimensional x-rays and bloodwork to understand how the virus affects lungs. We will further do immunological and inflammatory testing to understand why some people suffered lung damage and others did not. The information we gain will help patients, healthcare providers and decision makers understand how and why COVID affects the lungs and how it should be managed. It will also reveal how different COVID variants affect the lungs. We will use this new knowledge to write a formal guide on what respiratory monitoring, testing and management is needed after COVID-19 infection. This will ensure that people affected by COVID get the care they need to maintain lung health, which avoiding unnecessary testing and burden on the health care system.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",80405.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25918,429927,CovidFree@Home: Development and validation of a multivariable prediction model of deterioration in patients diagnosed with COVID-19 who are managing at home,"Millions of Canadians are anticipated to be infected with COVID-19 during this pandemic and many more will contract it in ongoing community transmission and/or a possible second wave. The majority of people who test positive for COVID-19 are sent home to isolate. In this population, deterioration of their disease can happen quickly and without warning, and we currently cannot accurately predict the approximately 20% who deteriorate and need hospitalization. From discussions with our patients and patient advisor, we know that people who are isolating at home feel terrified and alone. We need an effective and safe ambulatory care and research strategy for people with COVID-19 isolating at home. We are a team of heath care workers, patients, researchers and computer scientists (WearCOPD.ca; Can-BREATHE.ca) with five years of experience developing and using remote monitoring systems for respiratory disease. We have already built a smartphone application to facilitate the care of people with COVID-19 at home by allowing them to report their symptoms to their physician. With this project, we will expand our system to also include continuous smartwatch-based monitoring of heart rate, respiratory rate, cough, speech and other parameters. Sensor data will provide us with large volumes of objective data and allow us to build accurate real time machine learning models for predicting who needs to go to hospital. We will integrate these models into a dashboard that alerts clinicians of any patients that area getting worse, so that they can be called into hospital. Patients can be reassured that they are being followed thoroughly even though they are at home. Our system will also provide a platform for further research into how to prevent long term sequalae and preserve the health of people with COVID-19 who do not require hospitalization.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",372768.16,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P25920,466837,"Associations longitudinales entre le stress, l'anxiété et la dépression vécus par les personnes enceintes durant la pandémie et le développement de leur bébé: Le rôle de la relation conjugale et du soutien social","De nombreuses études démontrent qu'un niveau de stress élevé ainsi que des symptômes de dépression et/ou d'anxiété chez les personnes enceintes sont liés à des difficultés émotionnelles, comportementales et cognitives chez l'enfant. Les recherches montrent que la pandémie de la COVID-19 a exacerbé les taux de dépression et d'anxiété chez les personnes enceintes. De plus, un plus grand soutien perçu de la part du partenaire peut contribuer à améliorer le bien-être de la mère et de l'enfant suite à l'accouchement. Une meilleure compréhension des liens longitudinaux entre la détresse psychosociale chez les personnes enceintes et le développement de leurs bébés en contexte pandémique ainsi que le rôle modérateur de la relation conjugale et du soutien social servira à identifier des cibles de prévention pour atténuer les effets négatifs de la pandémie. Peu d'études ont examiné le bien-être des personnes enceintes tout au long de leur grossesse et après l'accouchement ainsi que certains facteurs pouvant avoir une influence sur leur bien-être. Ainsi, la présente étude vise à mieux comprendre les liens longitudinaux entre le stress, la dépression et l'anxiété vécus par les personnes enceintes en contexte pandémique et le tempérament et comportement de leur bébé. Le rôle modérateur de la relation conjugale et le soutien social du partenaire sera également examiné. Plus de 800 personnes enceintes ou à moins de 3 mois postnatal ont été recrutées afin de participer à cette étude d'une durée de 2 ans. Elles ont complété des questionnaires en ligne à chaque trimestre ainsi qu'à 3, 12, 18 et 24 mois postnatal. Ces résultats permettront d'identifier des pistes d'intervention auprès de cette clientèle en situation de vulnérabilité et favorisera le développement optimal de l'enfant.",,-99,Université du Québec à Montréal,13724.56,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25922,442997,Developing wise practices for a culturally safe rapid public health response to COVID-19 with Pikwàkanagàn First Nation,"The aim of this research is to understand how the Algonquins of Pikwàkanagàn ways of knowing can inform public health responses at local, provincial, federal and global levels, to mitigate the negative impacts of COVID-19 and maximize the health of Indigenous Peoples. At the time of writing this proposal, Pikwàkanagàn First Nation had no confirmed cases of COVID-19 despite high prevalence of people at risk. Our team includes an Algonquin First Nations Knowledge Keeper of traditional ways of knowing and practices, a health and social services supervisor within Pikwàkanagàn First Nation, and an Indigenous scholar from the First Nation with expertise in public health policy and sex and gender. We are using innovative methods to identify wise practices and inform culturally safe policies, programs, infrastructures and responses that include: sharing circles, journey mapping, photography and Anishinaabe symbol-based reflection, individual interviews and consultations. To facilitate a rapid response and impact, our knowledge translation plan involves the use of short video as part of a documentary film to rapidly create and share learnings and practices with a broad and diverse audience, in addition to disseminating summaries to Indigenous health forums, provincial and national health agencies and ministries. Deliverables can inform Indigenous and non-Indigenous governments and community members re-evaluate their own disaster mitigation approaches in pandemics or for future threats.",,-99,University of Ottawa,153826.27,Human Populations,Other,Adults (18 and older),Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2020 +P25924,459254,Surveillance des réponses immunitaires au vaccin contre la COVID-19 chez les personnes vivant avec le VIH-1,"People who are immunosuppressed or suffering from chronic inflammatory diseases have an increased risk of complications linked to SARS-CoV-2 infection, in addition to often having a diminished vaccine response. People living with HIV (PLHIV) also have chronic inflammation, which makes them more susceptible to complications. We will analyze the immune response of a cohort of 100 PLHIV vaccinated against COVID-19 and followed every six months at the UHRESS of the University Hospital of Quebec. Information on COVID-19 vaccination and risk factors leading to severe COVID will be collected. Serological and cellular immunity analyzes (innate and acquired) will be carried out at entry and at 6 months. A cohort of 200 vaccinated people working in retail (PTCD) and for whom we already have data will be used as a comparative group. We propose to complete this transdisciplinary analysis with the study of the innate immune response in PLHIV by analyzing neutrophil responses. Indeed, the human neutrophil being the most abundant leukocyte in the blood circulation and an important player in the development of the innate and inflammatory immune response, we hypothesize that measuring the intensity of the functional responses of the neutrophil could predict good vaccination protection, while being different between the cohorts of PLHIV and PTCD. This study will make it possible to characterize the elements of the innate immune response of PLHIV to the COVID-19 vaccine, in addition to establishing correlations between the cellular response and different serological markers, with the aim of suggesting or not a third dose of vaccine. or the addition of anti-inflammatory treatment. This project will be carried out by a multidisciplinary team covering clinical and fundamental aspects of virology, as well as functional immune responses including the neutrophil.",,-99,Université Laval,394293.95,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease susceptibility | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2021 +P25925,468874,Fostering workforce capacity to maximize opportunities for the digital transformation of public health in Canada,"COVID19 has shown us that the people working in public health need the skills to build digital tools like apps and websites and see if they work as they are supposed to. It is also important to make sure that these tools don't leave anyone behind and reach the people they are supposed to. While this is an important topic, we don't have a good idea of what skills people need or how they can be taught. We also don't have a good sense of how best to work with partners outside of the health system such as the businesses who are good at building these tools. In our study we hope to figure out the skills, training, and partners needed for people working in public health. To do this, we will study published suggestions and public health training programs made by experts around the world. We will use this information to know how far Canadian public health training programs are from the ideal. Then, we will discuss with Canadian public health trainers and experts to know how the gaps in our Canadian training programs can be filled and what partners will be needed to do so. We will use all this information to propose new skills, training and partners that can be included in our current training programs.",,-99,B.C. Centre for Disease Control (Vancouver),78410.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2022 +P25928,484622,Supporting COVID-recovery in primary care clinics serving equity-deserving communities,"Background: Since the pandemic, primary care clinicians are struggling to keep up with the added workload, meaning that chronic disease management and cancer screening rates are falling behind. This is especially true for primary care clinicians that do not have the support of interprofessional teams and are trying to care for equity-deserving communities. The Seamless Care Optimizing the Patient Experience (SCOPE) program is a provincial initiative offering a 'virtual' team to primary care clinicians so they can better support their patients. To date, SCOPE only supports ""reactive"" care; patients present to primary care with challenging problems, and then the primary care clinician calls a SCOPE hotline to access the team. COVID-related backlogs have highlighted the need to enhance this ""reactive"" support with ""proactive"" solutions that seek to close care-gaps in chronic disease management and/or cancer screening. Primary goal: To work with the trusted SCOPE platform to design an intervention to reduce health disparities by addressing care-gaps exacerbated by COVID. Approach: This project will follow an integrated knowledge translation (IKT) approach, as well as best-practice guidance for the design and evaluation of complex interventions. I will work collaboratively with an Advisory Network, informing all aspects of the project. Using methods from implementation science we will: 1) Explore barriers and facilitators of a proactive support(s) for primary care clinicians to ease primary care backlog; 2) Co-design a prototype for a proactive intervention; and 3) Refine the developed intervention with input from equity-deserving communities. Impact: This project will work in a collaborative manner to produce an iteratively refined and detailed implementation toolkit of proactive solutions to help with COVID-recovery, which will be presented to leaders of Ontario Health Teams.",,-99,Women's College Hospital (Toronto),79786.07,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25932,469843,"Aging, exercise, and sex: impact on the pathophysiology of ventilation-induced lung injury","Relevance: Our research focuses on a disease called Acute Respiratory Distress Syndrome (ARDS) in which the lung has difficulty getting oxygen into the blood, and that can be caused by lung infections, such as COVID-19. Approximately 30-40% of people with ARDS will die of the disease. Importantly, one of the key treatments for ARDS is mechanical ventilation, which is a treatment to help people breathe by pushing air into the lungs. However, mechanical ventilation can also cause more injury to the lungs. Problem to be addressed: To study ARDS and the damage caused by mechanical ventilation, we and many other laboratories use animals. Although great progress has been made, a problem with previous studies has been the standard practice of using young male animals for the experiments, even though in humans the disease occurs in both males and females and mostly within the older population. To overcome this limitation, we will investigate mechanical ventilation in older animals of both sexes that better reflect the human population. Experimental plan: For our studies, we will use aged male and female mice to study the development of lung injury. For example, we will utilize 22-month-old mice, which is comparable to a 65-year-old human, and study how the lungs of these animals respond to damage by mechanical ventilation. We will also examine the effects of exercise (running on a treadmill), since studies have demonstrated that regular exercise can protect against respiratory disease. Further, we will investigate various cellular pathways and molecules in the lung that are known to be important in ARDS. Impact: The novelty of our study is that we take a ""real life"" approach to scientific laboratory studies. With a better understanding of actual population-based issues that impact the development and/or the severity of ARDS, we will be better equipped to develop strategies to improve outcomes associated with this disease.",,-99,London Health Sciences Centre Res. Inc. (Ont.),592329.41,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2022 +P25933,460371,Co-designing action-oriented mental health conversations between care providers and aging Canadians in the community: mitigating the wider impacts of COVID-19,"The COVID-19 pandemic has worsened a pre-existing mental health crisis in Canada which has greatly affected older adults. It is critical that our health and social care systems are equipped to respond to the increased need for mental health support, care and treatment across the lifespan to prepare for future emergencies and pandemics. We partnered with older adults, caregivers, and health and social care providers during the COVID-19 pandemic. Over 1000 survey responses, and engagement of 52 workshop participants from across Canada led to the identification of a priority list of research questions on aging and mental health important to Canadians. Top priorities were the urgent need for skill-building in providers who are not mental health specialists and finding simple tools to support identification of mental health status. We identified the Mental Health Continuum (MHC) tool, which supports mental health reflection, monitoring and follow up. The MHC tool has been tested with young adults, but not older adults. Our proposed project aims to adapt the MHC tool and co-create and test processes for facilitating mental health conversations and follow-up actions in health and social care settings across Canada. In consultation with our Steering Committee of experts by lived experience, and our national team of researchers and partners, we propose a 3-phase study. We will conduct workshops and surveys with participants representing diverse experiences, and test the adapted tool and processes in 6 urban and rural communities across 3 provinces. We want to understand implementation and assess potential for broader impact. This project will act on priority research questions identified by Canadians during the COVID-19 pandemic, in response to the growing mental health crisis for Canada's diverse aging population. Results will lessen the impact of COVID-19 and build individual, community and system resilience in preparation for future health emergencies and pandemics.",,-99,"SE Health (Markham, Ontario)",402934.36,Human Populations,Unspecified,Older adults (65 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25936,487777,From Shadows to Spotlight: Providing Awareness and Recognition to Overlooked Canadian Health Care Workers,"The COVID-19 pandemic had a significant impact on the Canadian health care system, leading to challenges like burnout and staff shortages alongside rapid policy changes. While doctors and nurses were crucial during this time, so were other health care groups. In our recent CIHR-funded project, we examined a wide range of lesser-known health care groups (e.g., medical laboratory technologists and pharmacy technicians). Despite their role differences, one clear theme emerged from our work, which is that the general public and some policymakers have limited awareness of their job roles. This issue led to two stressors. First, policy changes, especially during the pandemic, affecting their ability to do their work properly. Second, they felt unappreciated despite their efforts to support patients during the pandemic. Our goal is to create a 30-minute documentary, uncovering the essential roles of these workers. To achieve this, we have partnered with a local hospital that permitted us to film in selected sites. We will interview various health care workers to find out about their job roles, what stressors they face, what they are passionate about in their work, and finally, what they would like the public to know about their work. To gain a multi-perspective, we will also interview members of their associations and engage citizen councils for insights and advocacy. By sharing their stories through the documentary, we aim to raise public awareness and appreciation for these vital health care workers. The Public Health Services Health & Safety Association will help promote and disseminate the documentary, ensuring it reaches a broader audience. Through this project, we hope to bridge the gap in understanding and recognizing the diverse roles contributing to the health care system's functioning.",,-99,University of Guelph,7606.24,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers | Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2023 +P25938,433597,Understanding Opioid Use and Harms among First Nations People in Ontario: Integrating Administrative Data with Guidance from Communities,"Harms related to opioid use have had devastating and long-lasting impacts on First Nations communities in Ontario, Canada. Yet, information on factors that contribute to these harms is limited and poses a critical barrier for communities who are working to identify evidence-based public health responses. Recent research led by the Chiefs of Ontario (COO) in collaboration with ICES and the Ontario Drug Policy Research Network (ODPRN) found that rates of opioid-related hospitalizations and deaths were up to four times higher among First Nations relative to non-First Nations in Ontario. From this work, the Opioid Surveillance Steering Committee, led by COO and comprised of First Nations community members and Elders, identified several essential research questions to better understand this health crisis. This research program will use databases at ICES to characterize the real-world patterns of opioid use and related harm, pathways of healthcare use, and treatment outcomes among First Nations people broadly, and in the context of the COVID-19 pandemic. Further, it will bring together community and research expertise through joint leadership by COO and the ODPRN. This will also support meaningful community engagement, direct liaisons between the research team and communities, and broad dissemination of research products tailored to various stakeholders at the community and policy-level. Rates of opioid-related harm in Ontario are among the highest in the country and First Nations people are disproportionately experiencing these effects. This program of research will provide First Nations communities with an understanding of the current state of the opioid crisis in their communities, how this is being impacted by the COVID-19 pandemic, and will identify opportunities for an evidence-based approach to public health and policy development with broad implications across Canada.",,-99,Unity Health Toronto,865893.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users | Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P25939,495275,A National Approach to Prioritizing Emerging Issues in COVID-19 in Transplantation,"Transplant patients have a higher risk of hospitalization, intensive care admissions, and death due to COVID-19 than the general population. The pace of the evolution of the pandemic has made it difficult to deliver research results in time to still be relevant for clinical and policy decision making. Consequently, decision makers must determine eligibility and recommendations for therapeutics often without any real-world evidence in prioritized patient populations. This inadequate evidence base has contributed to the high variability in transplant patients' access to therapies across the country. It has been very challenging for researchers to react quickly to emerging questions during the pandemic. The traditional research lifecycle of identifying questions, developing a proposal, securing funding, and setting up a study has proven slower than the pace of SARS-CoV-2 variant evolution and changes in practices and policies. Consequently, many investigators have found their original plans invalidated, infeasible, or the results were of limited eventual usefulness. In transplantation, smaller-scale, shorter-term, single-site studies have been the main source of knowledge. Such studies are quicker but are limited in their ability to inform issues such as therapeutic cost-effectiveness or patients' long-term recovery. To address this challenge, we have established a national, multi-disciplinary team and are developing an agile, collaborative framework to address emerging research questions and keep pace with the evolution of the pandemic. We are creating a prospective registry of over 2500 transplant patients and their caregivers and in this presentation, will share our progress on emerging questions on (1) therapeutic effectiveness and safety; (2) mental health, long-term well-being, and family impact; and (3) therapeutic cost-effectiveness and economic burden on the health care system and on families.",,-99,University of Alberta,1481.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2023 +P25940,480813,A national approach to prioritizing emerging research questions in COVID-19 in transplantation,"Transplant recipients are at high risk of severe COVID-19 outcomes. For transplant recipients surviving COVID-19 or experiencing the extreme stress associated with the pandemic, little is known about effective strategies to support recovery of quality of life. Understanding what is needed to support the health and quality of life of transplant recipients at particular points in time during the pandemic in Canada is challenging, given the pace of variant evolution and drug development, as well as regional variations in therapeutic practices and public health policies. Leveraging our pan-Canadian research network, we will create an agile, national framework that can address urgent and emerging issues, incorporating priorities of clinicians, researchers, and patients and families. We propose two national consensus-building forums six months apart, to determine the most urgent questions on emerging COVID-19 prophylactics/therapeutics in transplant patients. The outcome of these forums will be used to direct studies using a prospective registry we are developing of over 2500 transplant patients and their families. Our design will enable us to assess the safety, efficacy, and cost-effectiveness of therapies in transplant patients, considering short and long-term clinical outcomes, and other outcomes critical to patients and their families, including mental health, life participation, and financial burden. Through a consensus-based, multi-disciplinary approach to establishing priority research questions, this project will enable our research team to provide the actionable knowledge needed by policymakers, for clinical guidelines, and by transplant patients and their families.",,-99,University of Alberta,15007.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Policy research and interventions | Indirect health impacts,2023 +P25941,460291,"Addressing rising Canadian radon gas-induced lung cancer risk due to COVID-19 pandemic-linked lung injury, disability, and behaviour change","Our goal is to understand and address rising radon gas-induced lung cancer risks due to COVID-19 pandemic-linked lung injury, disability, and behaviour change. 1 in 5 lung cancers arise in Canadians who have never smoked, with ~110,000 cases since 2001. A previous lung disease history is directly associated with increased lung cancer risk in never-smokers, making them more vulnerable to triggers. The most common lung cancer trigger in never-smokers is repetitive inhalation of radioactive radon gas, a prevalent carcinogen in the Canadian residential environment that emits highly mutagenic particle radiation. The amount of life spent 'at home' correlates with radon exposure, modifying lung cancer risk as a function of our behaviour and built environment. Young people and the 6 million Canadians living with disability were, even before the pandemic, exposed to more radon due to biases in how they are able access housing stock. Today, fully 1 in 5 people hospitalized with COVID-19 are returning to their lives with a new disability, as lung and heart injury increases prevalence of debilitating fatigue, cognitive impairment, and reduced mobility; collectively, these alter employment prospects, behaviour, and time spent at home. For others, COVID-19-related behaviour changes such as heightened demand for long term telecommuting is changing radon exposure, with a 20% increase in particle radiation dose to lungs recorded for 18-45 year-olds so far. In this project, we will (1) measure radon exposure of Canadians experiencing COVID-19-induced disability and/or behaviour change, as a function of personal demographics, employment sector, job profile and across the built environment; (2) estimate radon-induced lung cancer burdens and costs in a pandemic-modified future with/without intervention for impacted groups; and (3) develop, for the first time, radon reduction resources for those living with disability, with a focus on COVID-19 survivors and promoting healthier cities.",,-99,University of Calgary,367380.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +P25943,450258,GA4GH Genomic Data Sharing Tools Against COVID-19,"The COVID-19 outbreak has highlighted the need for genomic data standards in order to enable the rapid sharing of high quality genomic and health data. Researchers have shared viral and host sequence data at an unprecedented pace, a first step in creating vaccines in record time. Simultaneously, the cost of genome sequencing continues to decrease, yielding millions of samples in the coming years from both research and healthcare. Sharing of this data is necessary to understand human diseases and eventually help patients. Strengthening international standards over time will prepare us to more effectively respond to future outbreaks as well as advance basic biology and inform clinical care across a range of disease areas. Doing so requires the community to agree on common methods for collecting, storing, transferring, accessing, and analyzing data. The Global Alliance for Genomics and Health (GA4GH) was established in 2013 to accelerate progress in genomic research and human health by cultivating a common framework of standards and harmonized approaches for effective and responsible data sharing. GA4GH brings together 1,000+ individual contributors and 660+ organizational members across 35+ countries working in the areas of healthcare, research, patient advocacy, life science, and information technology to deliver genomic data sharing standards and frameworks. This proposal will provide support for the GA4GH to bring in additional personnel, support the existing team, and drive engagement with the Canadian COVID research community. GA4GH will develop, refine, and adapt GA4GH standards and open-source tools to facilitate research data sharing for COVID applications and the greater infection disease community. Collectively, these efforts will ensure the rapid and timely research response to the current phase of the COVID-19 pandemic in Canada and around the globe, which will be heavily impacted by emerging variants of concern.",,-99,"Ontario Institute for Cancer Research (Toronto, Ontario)",527098.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P25950,488386,Hypersomnolence disorder in post-acute COVID-19 syndrome,"Between 10 and 30% of adults present multidimensional and disabling symptoms that persist weeks to years after a SARS-CoV-2 infection, a condition referred to as post-acute COVID-19 syndrome. Fatigue, muscle weakness, and sleep disturbances are the most frequent symptoms. Among these patients, a subgroup reports abnormally long sleep duration, difficulties waking up in the morning, and excessive daytime sleepiness. Yet, we don't know if these patients have a central hypersomnolence disorder secondary to their Covid-19 disease and whether they have objective markers of hypersomnolence when tested in the laboratory. In the proposed project, we will verify whether patients with post-acute COVID-19 syndrome and hypersomnolence complaints have objective markers of hypersomnia when tested with standardized protocols. We will determine whether hypersomnolence symptoms are explained by abnormal sleep or obstructive sleep apnea. We will verify whether hypersomnolence symptoms are associated with a particular immune and inflammatory profile when compared to patients with post-acute COVID-19 syndrome but without hypersomnia, and healthy control subjects. We will also follow these patients over a period of 12 months to document symptoms evolution. This project could have significant clinical impacts, as medical clinics receive a growing number of referrals for patients with post-acute COVID-19 syndrome complaining of disabling sleepiness and abnormally long sleep duration. This project has the potential to reduce the post-acute COVID-19 syndrome burden as sleep disorders probably contribute to worsening of fatigue, psychological distress and cognitive dysfunction. Sleep could therefore be a target for treatment.",,-99,CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur,585234.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P25951,460334,Effects of a personalized musical intervention on the mental health impacts of COVID-19 in older adults,"Since the start of the pandemic, 43% of Canadians aged 65 and over have reported increased isolation and loneliness, factors that exacerbate stress, anxiety and depression. As music soothes and improves mood, it is proving to be an effective intervention to reduce these impacts. This project seeks to establish a portrait of the impacts of COVID-19 on the mental health of seniors in Canada and the psychological effects of listening to music. Preliminary data from an online survey confirm the deterioration of psychological health and the stress of catching COVID-19 or contaminating loved ones. Benefits of music in alleviating loneliness and stress are reported particularly among seniors who have screened positive for anxiety or depression. This suggests that listening to music is an effective tool to mitigate the impacts of the pandemic on the mental health of seniors. This project will also test the effectiveness of a personalized musical intervention on the mental health of isolated seniors who have screened positive for anxiety or depression. Half of them will listen to personalized music (music group) and the other half to audio books (comparison group). These two interventions will take place for two months, four days a week. Before and after the intervention, cortisol, the stress hormone, will be measured in hair samples; then the perception of stress, anxiety and depression will be measured with questionnaires. Cortisol and the perception of stress, anxiety and depression are expected to be lower in the music group than in the comparison group. This project will help to better understand the impacts of COVID-19 on the mental health of older adults. It will also evaluate the effectiveness of an accessible and enjoyable non-pharmacological musical intervention to reduce the impacts of pandemics on the mental health of older adults.",,-99,Université de Montréal,249027.25,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25952,481269,"Learning from mpox: Community-Based Mixed Methods Research to Support Intersectional and Stigma-Informed Approaches to Pandemic Preparedness for Gay, Bisexual, Queer, and Other Men who Have Sex with Men in Canada","Mpox (formerly referred to as monkeypox) was declared a public health emergency of international concern in July 2022. The overarching objectives of our interdisciplinary research team are to: Understand mpox experiences and perspectives of diverse gay, bisexual, queer, and other men who have sex with men (GBQM) across Canada, including disease progression, vaccine confidence, health-seeking behaviours, and the impact of mpox on social and sexual lives (including, albeit not limited to, GBQM diagnosed with mpox); (2) Explore challenges in responding to, controlling, and mitigating the impact of mpox from the perspective of health system stakeholders; and (3) Implement an integrated knowledge translation strategy that engages community and public health partners to develop and mobilize intersectional and stigma-informed approaches to pandemic preparedness for GBQM communities. Our proposed population-focused research is crucial given that GBQM have historically experienced significant disparities in physical, mental, and sexual health, amplified by systemic marginalization and high barriers to healthcare and were the communities most impacted by mpox in Canada. This CIHR grant provides a unique opportunity to leverage established research infrastructure and address all three objectives of the funding opportunity through embedding mpox research within ongoing community-based research with GBQM in Canada. Our study design, sampling strategy, study population, and other interdisciplinary methods are distinct strengths of our proposed study. Our capable team includes researchers, clinicians, and knowledge users who share an interest and expertise in HIV prevention, COVID-19, and mpox research for GBQM. The proposed mpox research will provide important information to both understand the mpox response and the experiences of GBQM and health system stakeholders, and to develop and mobilize interdisciplinary approaches to pandemic preparedness for marginalized communities.",,-99,University of Toronto,375198.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Clinical | Non-Clinical,Not applicable,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts | Evaluation of elimination strategy implementation in different contexts.,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Communication | Policy research and interventions,2023 +P25954,448862,Post-Acute Sequelae of COVID-19: An Electroencephalography and Magnetic Resonance Neuroimaging Study of the Elderly in our Communities,"As the Covid 19 pandemic continues, it is becoming clear that very many people are being affected by ""long-haul"" symptoms, after they are no longer infectious. The long-haul symptoms, including fatigue, brain fog, and cognitive and psychiatric complaints suggest that COVID-19 is having an impact on the brain. Literature is suggesting that possibly hundreds of thousands of Canadians and millions of people around the world could ultimately struggle with these symptoms, which impact activities of daily living and quality of life. It is expected that the elderly living in our communities will be particularly impacted, as they are at elevated risk of infection and are particularly susceptible to COVID-19. Although much attention has been paid to the risks of COVID-19 for the elderly in long-term care, community-dwelling older adults are very important to study because they may be at elevated risk of cognitive decline due to COVID-19, placing additional burden on caregivers and the health care system. Typically under-served by clinical health research, this important sector of our society is the particular focus of the proposed research. We are undertaking a project called NeuroCOVID19, that encompasses behavioural assessments of sensation, cognition and emotion; symptom self-reports; electroencephalography (EEG) of the electrical signals of the brain; and magnetic resonance imaging (MRI) of the brain. We will apply NeuroCOVID19 to measure the effects of long-haul COVID-19 in the elderly living in Toronto communities, in comparison to a control group of elderly individuals who were not infected. From this work we expect to improve understanding of how COVID-19 affects the brain in the elderly, and to translate this knowledge so that patient-specific brain treatments can be implemented to improve the health of very many Canadians.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",397222.41,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P25959,467884,Access to HIV and sexual healthcare during COVID-19: gay and bisexual men's experience,N/A,,-99,University of Western Ontario,2092.85,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25960,481268,Pre-exposure mpox vaccination campaigns aimed at GBTMSM+ and sex work communities: What worked in 2022 and what can we learn to strengthen future targeted vaccination campaigns to stigmatized communities in infodemic times?,"In 2022, Canada was among many countries to experience unexpected mpox outbreaks, primarily in communities of men who have sex with men (MSM+ communities). Since the smallpox vaccine can prevent mpox, the National Advisory Committee on Immunization recommended vaccination for those identified as at highest risk of mpox: MSM+ (including trans, Two Spirit, and non-binary individuals who identify as gay/bisexual/pansexual) or sex workers with multiple sexual contacts or other risk factors. This study aims to assess targeted vaccination campaigns against mpox in 2 Canadian provinces (QC, BC) that have substantial cultural, geographic, and linguistic differences and experienced slightly different disease epidemiology, yet together account for approximately half of all Canadian mpox cases. Specific objectives are to: 1) Assess perceptions of the disease and vaccine among populations recommended to receive preventive vaccination, as well as healthcare providers and community workers who serve these groups; 2) Examine drivers of mpox vaccination decisions and experiences; 3) Describe public health strategies and interventions that were implemented to enhance vaccine acceptance and uptake. Data will be collected through interviews and document collection, and analyzed using reflexive thematic analysis. We will conduct interviews with members of communities recommended for preventive vaccination and with workers who participated in vaccination campaigns. An environmental scan looking at how, when and where campaigns took place, the communication and information tools used, and the modes of delivery will be conducted through document analysis. This assessment of targeted mpox vaccination campaigns will inform future efforts to tailor and deliver accurate information, and combat misinformation, about vaccination and other preventive health measures to MSM+, GLBTQTSIA+, sex workers, with potential implications for communication with other stigmatized groups.",,-99,University of British Columbia,374950.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Indigenous People | Sexual and gender minorities | Sex workers | Other,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts | Evaluation of elimination strategy implementation in different contexts.,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions,2023 +P25961,499054,Building trusted population health information systems and interventions,"From mpox to measles, vaccination is one of our best ways of controlling infectious disease outbreaks. However, barriers to vaccination-including misinformation-driven distrust in those providing vaccination and lack of confidence in vaccine safety or effectiveness-threaten our ability to stop epidemics. Many of these barriers may be reduced by improving our use of information to build trusted population health information systems: providing more accessible, credible, culturally-acceptable vaccine communication to counter mis- and disinformation that pollutes the vaccine communication ecosystem and conducting more thorough and transparent surveillance of vaccine coverage, safety, and effectiveness in diverse populations. I will fill current knowledge gaps in our understanding of effective health communication interventions and trusted surveillance systems that build long-term trust with populations through an integrated program of population health information intervention research focused on vaccination. My objectives are to: 1. Improve our understanding of what makes for effective population health information interventions, including communication and surveillance campaigns and technologies that are understood as trusted and trustworthy by the public. 2. Use community-based research, conducted in partnership with community organizations, people with lived experience, and health or social service providers, to evaluate and improve population health information interventions, including those targeting critical information literacy as well as those aiming to build trusted information and communication relationships between public health and populations. 3. Strengthen multidisciplinary collaborations between health and information scientists, researchers and practitioners, to better understand and address mis- and disinformation and what builds critical health literacy and trust in evidence-based information sources amidst polluted information ecosystems.",,-99,University of British Columbia,851777.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2023 +P25962,486357,Investigating the role of antigen-specific regulatory T cells in SARS-CoV-2 infection and immunization,"Infection by SARS-CoV-2 results in COVID-19, a disease driven by immunopathology -- damaging inflammation to the infected individual caused by their own immune system. Conventional T-cells are cells that protect our body from pathogens by boosting inflammation and killing infected cells; they are crucial for protection in SARS-CoV-2 infection but can contribute to immunopathology in severe COVID-19. Regulatory T(REG)-cells are immunosuppressive cells that act on conventional T-cells to prevent out-of-control antiviral responses causing immunopathology. Conventional T-cells and TREG-cells function by specifically recognizing one single protein fragment, ie. a section of the SARS-CoV-2 virus, to identify infected target cells and harmful conventional T-cells respectively. The role of SARS-CoV-2-specific TREG-cells in SARS-CoV-2 infection and severe COVID-19 remains unknown. We hypothesize that the SARS-CoV-2-specific TREG-cells in severe COVID-19 are insufficiently curtailing the exaggerated inflammation due to dysfunctional suppressive activity. We are interested in identifying the magnitude of SARS-CoV-2-specific TREG-cell response (the number of responsive cells), the TREG phenotype (the subtype of TREG-cells responding) and their suppressive capacity (the ability of responsive TREG-cells to prevent the activity of conventional T-cells). We will investigate this response in a range of severities, from asymptomatic individuals to severe COVID-19 patients admitted to the ICU. Our characterization of TREG-cells will enable us to better understand the role of TREG-mediated immune regulation in severe COVID-19. By identifying efficiently suppressive TREG populations, our findings will contribute to the development of TREG-based therapies in pulmonary disease.",,-99,University of Toronto,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2022 +P25963,480546,Integrated Care Clinical Pathway Implementation using a Patient Oriented Learning Health System Approach: A Realist Process Evaluation of the Saskatchewan Long COVID Pathway,"Clinical pathways (CPW) are designed to organize patient care through the health system and optimize delivery and patient outcomes. However, implementing these processes successfully in practice can be challenging. In Saskatchewan, a Long COVID (LC) CPW, established by the Saskatchewan Health Authority (SHA), aims to improve care for patients suffering with LC. Since LC symptoms are diverse, patients may need to be referred to a range of health professionals across the care continuum and services for diagnosis and treatment. This project aims to evaluate how, why, under what circumstances, and for whom the LC CPW works in order to scale it up across all 38 Health Networks in Saskatchewan. In partnership with SHA, we will continuously learn and improve as we apply a realist research approach to our evaluation of the operation of a patient-oriented Learning Health System. By taking a realist research approach, our team can provide our SHA partner with evidence to understand what makes a successful, economically efficient, and sustainable LC CPW. The Implementation Science Team (IST) for the project is comprised of patient partners, researchers, health care providers, and health system leaders who will complete an evaluation through five phases: 1) Planning, 2) Initial Theory Development, 3) Theory Testing, 4) Learning Cycles, and 5) Theory Refinement. We will collaborate and strengthen relationships using inter-agency collaboration and build trainee skills within the IST who are diverse in their backgrounds, expertise, age, sex, and ethnicity. The project will ensure research findings are relevant to patients by engaging patient partners at all phases of the research. Our key stakeholders and SHA partner will use evidence from the evaluation to inform policy decisions to scale-up the LC CPW across the province and develop a sustainable framework for future CPWs in Saskatchewan and Canada.",,-99,University of Saskatchewan,725801.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health service delivery | Health workforce,2022 +P25965,486367,Recovering from the COVID-19 pandemic: Evaluation of a group intervention with young people in clinical and social psychology,"This study will evaluate the effectiveness of a community intervention of six group workshops for adolescents and young adults. The intervention was set up by the InterCom Project and is delivered by trained facilitators. It aims to equip participants in a context of current (COVID-19 pandemic) or future social change based on clinical and social psychology. This research project will take place in three phases. 1) A qualitative study will be conducted with 100 participants to analyze the degree of satisfaction (measured by questionnaire) and written comments from participants. 2) A quantitative pilot study will be conducted to measure the effectiveness of the workshops with 60 participants. The effectiveness of the intervention will be evaluated by examining change on the following psychological measures: self-esteem, well-being, identity clarity, resilience, cognitive flexibility, optimism, self-compassion, empathy and open-mindedness. The change will represent the difference between the responses on the measures before starting the workshop series, at the end of the sixth (final) workshop and 2 months after the end of the last workshop. 3) The main study will be conducted with 200 participants to assess the change in participants on the above-mentioned measures. In addition, a just-in-time adaptive intervention (JITAI) will be added in one of the two experimental groups. The just-in-time adaptive intervention will consist of sending text messages between workshops to capture the individual's psychological state and provide support adapted to their state. The benefits of JITAI will be assessed by comparing participants who received the workshops to those who received the workshops and JITAI.",,-99,Université de Montréal,13021.09,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2022 +P25969,494305,Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus Infections Prior to and During the COVID-19 Pandemic,"The World Health Organization has declared antimicrobial resistance a major global health threat and lists methicillin-resistant Staphylococcus aureus (MRSA) as a priority pathogen. MRSA can cause severe infections and spreads by direct contact with infected individuals or contaminated surfaces or medical devices. Originally, MRSA mostly affected people in hospitals, but is now also common in the community. Hospital and community-associated MRSA strains differ, where hospital strains are resistant to more antibiotics and community strains can spread more easily and cause severe skin and soft tissue infections. However, in recent years, these strains have been found in both settings. This is concerning because MRSA can easily pick up beneficial genes from other bacteria, and the movement of these strains between settings poses the risk of more deadly MRSA infections that are highly resistant to antibiotics and easily spread. In Canada, MRSA is not regularly tracked outside of healthcare settings, and its genetic analysis has not been done on a population level. Our project aims to study MRSA genetics by analyzing samples collected from infected individuals across Ontario, including both hospital- and community-associated MRSA. We believe the COVID-19 pandemic and related public health measures may have affected the types of MRSA strains that are spread in the population. By studying samples collected before and during the pandemic, we can better understand MRSA strains and identify genetic features that may help some of them survive antibiotic treatment and cause more serious disease. This information is critical for targeted interventions to stop the spread of MRSA. This project will provide a foundation for MRSA genetic studies in the post-pandemic era that can be used across Canada.",,-99,University of Western Ontario,73558.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P25977,450714,Canadian Immunization Research Network: directed grant extension,"The Canadian Immunization Research Network (CIRN) is a collaborative national research network that brings together more than 150 investigators from 58 institutions across Canada. CIRN comprises eight subnetworks built to provide research capacity that is responsive and scalable to undertake research during an infectious disease crisis such as a pandemic and to provide public health with Canadian-relevant vaccine-related research for public health decision-making. As a network of networks, CIRN is undertakes clinical research, surveillance and epidemiological research, and public health program evaluation. The eight subnetworks are the Clinical Trials Network (CTN), Serious Outcomes Surveillance Network (SOS), Canadian National Vaccine Safety Network (CANVAS), Special Immunization Clinics Network (SIC), Provincial Collaborative Network (PCN), Reference Laboratory Network (RLN), Modeling and Economics Research Network (ModERN), and Social Sciences and Humanities Network (SSHN). The extension proposal of CIRN will focus on both non-COVID-19 research activities and COVID-19 research activities. Research areas addressed for the CIRN extension proposal include: (A) rapid evaluation of candidate vaccines for safety and immunogenicity including COVID-19 vaccine clinical trials; this priority will be met through studies undertaken by CTN, SIC and SOS; (B) population-based methods to evaluate vaccine effectiveness and safety; this area will be met by studies undertaken by CANVAS, RLN, and PCN; (C) research on interventions that can help to improve vaccine acceptance, hesitancy and uptake including consideration of priority research projects to inform current and future policy; this area will be addressed by studies undertaken by SSHN; (D) population prioritization, modeling, and knowledge mobilization that support development and roll-out of public health vaccination strategies; these objectives will be addressed through by studies undertaken by ModERN, and (E) coordination and information sharing objectives will be coordinated by the Network Management Office (NMO).",,-99,Dalhousie University (Nova Scotia),4865527.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Characterisation of vaccine-induced immunity | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2021 +P25979,475524,An equity-based examination of access to follow-up care from psychiatric hospitalization before and after the introduction of Ontario's new physician billing structure for virtual care,"Mental health disorders are common among Canadian youth with high rates of hospital readmission. Timely follow-up care following psychiatric hospitalization improves outcomes but its uptake is poor and inequitable. While Health Quality Ontario issued a standard for adolescents with depression to receive follow-up care within 7 days of discharge, Ontario hospitals are not consistently following this standard. Virtual care may reduce barriers to follow-up care but may also increase inequities. During the COVID-19 pandemic, a new billing structure was implemented which formalized the use of virtual care. Whether this change in billing structure impacts access to follow-up care for children/adolescents is unknown. This study aims to determine patterns of virtual follow-up care access before and after the introduction of Ontario's billing change as well as characteristics (socioeconomic status, gender, location and immigrant status) of those receiving virtual follow-up care. The research will characterize hospital-level patterns regarding the provision of follow-up care and examine reasons for these differences from the perspective of healthcare personnel. A mixed methods approach will be used. For the quantitative portion, health administrative data at ICES will be analyzed to determine changes in rates of virtual follow-up care for children/adolescents before and after the new billing structure. These data will be used to determine characteristics of those receiving follow-up care and to identify hospital-level patterns. Qualitatively, interviews will be conducted with hospital physicians who refer to follow-up care and leaders from high and low performing hospitals. The study will provide evidence on how virtual care impacts the provision of follow-up care and whether it is delivered equitably. It will identify whether and why variations exist across hospitals regarding follow-up care for children/adolescents following psychiatric hospitalization.",,-99,Hospital for Sick Children (Toronto),77083.46,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health information systems,2022 +P25981,438751,Préserver le lien des résidents en ESLD atteints de troubles cognitifs avec leurs proches en contexte de pandémie : évaluation de la mise en œuvre et des effets d'interventions virtuelles et en personnes,"In Quebec, nearly 70% of deaths linked to COVID-19 are people living in long-term care establishments (ESLD). The restrictions imposed to reduce the transmission of the virus have deleterious effects on the elderly and consequences on caregivers. In order to mitigate the negative effects, different strategies are used to preserve contact with loved ones and thus promote protective actions for the mental and physical state of seniors. However, the evaluation of the implementation and effects of innovative interventions in the context of a pandemic in older adults with cognitive disorders have not been studied to date in Canada. In collaboration with 5 partner ESLDs, the goal of the project is to evaluate the implementation process, the viability and acceptability of interventions aimed at favoring the presence of loved ones (in person or virtually), as well as the effects on residents, their loved ones and related costs. An evaluative research design is preferred. A multiple case study will be used to describe the reality of the targeted environments and actors, understand the complex relationships between the different factors, and document the degree and variability of implementation in the different environments and their results. Residents with cognitive disorders, their caregivers and members of the care team will be recruited in each setting. Interventions to maintain contact with loved ones and supported by the living environment can mitigate the repercussions of isolation and have a considerable impact on anxiety, cognitive and behavioral symptoms and quality of life. By giving voice to elders, relatives and care staff, the documentation of acceptability will add evidence that adapted, humane interventions are viable and relevant in LTCFs.",,-99,Université Laval,38032.34,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Caregivers,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts,2020 +P25982,438752,Preserving the connection of ESLD residents with cognitive disorders with their loved ones in the context of a pandemic: evaluation of the implementation and effects of virtual and in-person interventions,"In Quebec, nearly 70% of COVID-19-related deaths are people living in long-term care facilities (LTCFs). The restrictions imposed to reduce the transmission of the virus have harmful effects on the elderly and consequences for caregivers. In order to mitigate the negative effects, different strategies are used to maintain contact with loved ones and thus promote actions that protect the mental and physical state of seniors. However, the evaluation of the implementation and effects of innovative interventions in the context of a pandemic among older adults with cognitive disorders has not been studied to date in Canada. In collaboration with 5 partner LTCFs, the goal of the project is to evaluate the implementation process, the viability and acceptability of interventions aimed at prioritizing the presence of loved ones (in person or virtually), as well as the effects on residents, their loved ones and the related costs. An evaluative research design is preferred. A multiple case study will be used to describe the reality of the targeted settings and actors, grasp the complex relationships between the different factors, document the degree and variability of implementation in the different settings and their results. Residents with cognitive disorders, their caregivers and members of the care team will be recruited in each setting. Interventions that preserve contact with loved ones and are supported by the living environment can mitigate the repercussions of isolation and have a considerable impact on anxiety, cognitive and behavioural symptoms and quality of life. By giving voice to seniors, loved ones and care staff, the documentation of acceptability will add evidence that adapted, humane interventions are viable and relevant in LTCFs.",,-99,Université Laval,3803.23,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts,2020 +P25983,478781,Implementing best practices in long-term care settings: Strategies to guide health services and policies,"Long-term care (LTC) homes saw an unprecedented number of COVID-19 infections and deaths across Canadian provinces and territories. Long-standing deficiencies in the LTC sector contributed to this crisis. Translating evidence-based practices into clinical and policy contexts is a challenge. Policymakers in LTC require information adapted to their context to improve patient experience, population health, the well-being of the care team, healthcare costs and equity. To ensure that policies are based on the latest scientific evidence, research findings must be made available, accessible, and useful to policymakers to help inform decision-making. This project aims to develop a policy brief that offers viable policy options to support decision-making, preparation and implementation of evidence-based practices in LTC. Based on the results of a previous pan-Canadian study, deliberative process and interviews with policymakers, managers, health care professionals involved in LTC, residents or their representatives, a draft a policy brief will be developed. Participants will meet in a virtual policy workshop to present and discuss new research evidence and draft policy options. Finally, a final version of the report will be created based on the comments received during the virtual workshop. This process will allow for a clear and concise language; academic and technical jargon should be drilled down into plain and non-academic language. The policy brief will consider important dimensions such as feasibility, costs, and other pros and cons for a better decision process. A policy brief for the implementation of innovations in LTC, which can support decision-making and give concrete strategies to decision-makers, is necessary to improve patient experience, population health, care team well-being, and healthcare costs.",,-99,Université Laval,54827.59,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P25984,475151,Implementing best practices in long-term care settings: Strategies to guide health services and policies,"Long-term care (LTC) homes saw an unprecedented number of COVID-19 infections and deaths across Canadian provinces and territories. Long-standing deficiencies in the LTC sector contributed to this crisis. Translating evidence-based practices into clinical and policy contexts is a challenge. Policymakers in LTC require information adapted to their context to improve patient experience, population health, the well-being of the care team, healthcare costs and equity. To ensure that policies are based on the latest scientific evidence, research findings must be made available, accessible, and useful to policymakers to help inform decision-making. This project aims to develop a policy brief that offers viable policy options to support decision-making, preparation and implementation of evidence-based practices in LTC. Based on the results of a previous pan-Canadian study, deliberative process and interviews with policymakers, managers, health care professionals involved in LTC, residents or their representatives, a draft a policy brief will be developed. Participants will meet in a virtual policy workshop to present and discuss new research evidence and draft policy options. Finally, a final version of the report will be created based on the comments received during the virtual workshop. This process will allow for a clear and concise language; academic and technical jargon should be drilled down into plain and non-academic language. The policy brief will consider important dimensions such as feasibility, costs, and other pros and cons for a better decision process. A policy brief for the implementation of innovations in LTC, which can support decision-making and give concrete strategies to decision-makers, is necessary to improve patient experience, population health, care team well-being, and healthcare costs.",,-99,Université Laval,109652.98,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P25987,457363,"Workload management through understanding and addressing resident needs in long term care: A study to adapt, validate, implement and evaluate the Synergy Model","COVID-19 has exacerbated work overload in a female dominant and racialized sector, long term care (LTC). Heavy workloads are attributed to persistent workforce challenges in LTC, such as inadequate staffing. Ineffective workload management is costly for the health and safety of LTC staff (e.g. burnout), residents (e.g. missed care), family caregivers (e.g. anxiety) and the organization (e.g. turnover). LTC staffing decisions are based on arbitrary guidelines (e.g. 4.1 hours per resident per day) instead of resident needs. This study will adapt, validate, implement and evaluate a real-time assessment tool based on residents' acuity and dependency needs. Resident assessment scores will be used to make evidence-informed staffing assignments and workload decisions. A steering committee of key stakeholders, including residents and family members, will be established at the start of the study to inform the direction of the research. The Synergy Model consists of a validated assessment tool, the synergy tool, which can be adapted to different healthcare sectors. The tool measures eight characteristics: five acuity characteristics (e.g., complexity, stability, vulnerability) and three dependency characteristics (e.g., participation in activities of daily living). Acuity and dependency scores for individual patients are used to optimize staffing decisions (i.e., what team member (s) should provide care for residents based on their synergy scores?). Extensive use of the synergy tool in acute care settings has been linked to positive outcomes for patients, staff and organizations. The tool has never been used in LTC. In this study, we will adapt the tool for LTC residents and use it in three LTC partner homes. We will use surveys and administrative data and focus groups from multiple sources (i.e., residents, families, staff, organization) to evaluate tool use impact on workload management and resident care, and we will identify implementation facilitators and barriers.",,-99,University of British Columbia,78955.97,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery | Health workforce,2021 +P25989,438276,"Virtual primary care: a multi-provincial mixed methods study of access, experiences, and outcomes","Timely access to high-quality primary care is an ongoing problem across most Canadian provinces. Virtual care - consulting with a health care professional remotely using communication or information technology such as telephone, videoconference, or text messaging - has the potential to increase access, improve quality, and reduce costs; however, it has not been widely available in Canada and has not been widely studied. The COVID-19 pandemic has led to a rapid move away from in-office visits and towards virtual care, raising significant questions about the impact of virtual care on patients, health care professionals, and the health system more broadly. This project will use information from interviews with health professionals (physicians, nurse practitioners and nurses) and patients; routinely collected, population-based health service delivery data; and provincial policy documents to study access to, experiences with, and outcomes from virtual care provided in the primary care context across four Canadian provinces. Building on existing surveys and interviews being conducted in Ontario and Nova Scotia, the interviews with patients and health professionals will explore experiences with providing and receiving care virtually. The analysis of routinely collected health service data will identify what groups of patients are receiving care virtually, and for what health concerns. We will use these same data to look at downstream health outcomes and to measure the overall impact of virtual care on the volume of services delivered and on health system costs. Ultimately, this project will strengthen our understanding about the impact of the move toward virtual care on patients, providers, and the health care system, supporting the development of coordinating provincial policies. This will help to ensure that patients have access to the primary services they need, virtually or in person, at the right time.",,-99,"Simon Fraser University (Burnaby, B.C.)",74711.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff | Physicians | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +P25990,460235,Advancing virtual primary care for people with opioid use disorder,"British Columbia continues to grapple with dual public health emergencies: the COVID-19 pandemic and the opioid-related overdose crisis. Pandemic-related public health guidelines have rarely recognised the need to modify approaches to support communities that experience marginalisation, including individuals with opioid use disorder (OUD). One example is the broad move to virtual forms of primary care, which may compromise healthcare access for people with OUD, who frequently face concurrent challenges of poverty and insecure housing or homelessness, making make accessing a virtual visit difficult. Compromised access to primary care may interrupt OUD treatments and may worsen co-occurring health problems such as HIV, Hepatitis C and mental health issues, ultimately leading to increased morbidity and mortality. We propose a two-year study to characterize changes to primary care access and to assess patient outcomes following the rapid introduction of virtual care for people with OUD. We have three research objectives: 1) To document the experiences and perspectives of a) people with OUD navigating access to virtual visits, and b) clinicians providing virtual visits during the pandemic; 2) To describe the uptake of virtual care, its impact on access and downstream health outcomes for people with OUD; and 3) to co-create a suite of educational resources for clinicians and people with OUD that support equitable access to virtual primary care. The project will include analyses of administrative health data, interviews with people with lived/living experience of OUD and their clinicians, and facilitated group dialogues. This work will enhance understanding about the impact of virtual models of care on people with OUD. Findings will be used to shape best practices for implementing virtual care amongst communities that experience marginalisation, both in future public health emergencies and as part of regular primary care.",,-99,"Simon Fraser University (Burnaby, B.C.)",317488.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P25996,486452,Exploring the Impacts of Telemedicine on Access to Sexual and Reproductive Health Care for 2SLGBTQ+ and Rural Populations,"Telemedicine or telehealth was globally introduced during the COVID-19 and has become increasingly recognized to improve efficiency and accessibility for health services. Sexual and reproductive health (SRH) services are uniquely impacted by telehealth practices; lack of resources and stigmas surrounding accessing SRH services makes telemedicine a promising approach to improve patient care. However, technology related barriers decrease the quality of care when utilizing telehealth services and remote appointments have reduced availability of in-person appointments at local clinics. Studies exploring the distinctive impacts of telehealth on sexual health services are limited and often leave out vulnerable populations. This research aims to address the benefits and drawbacks of telemedicine for rural and 2SLGBTQ+ populations. As mandates are removed in the post-COVID era, this study seeks to ensure marginalized groups are included in future policy making regarding telehealth services for SRH. Interviews will be conducted with rural and 2SLGBTQ+ adults who have accessed telehealth services during the pandemic to gain an understanding of how this technology has impacted personal experiences. Statistical data regarding appointment availability and attendance will be collected from local clinics to evaluate the efficacy of telemedicine in SRH. These finding will provide a holistic understanding of how SRH care for rural and 2SLGBTQ+ populations have been impacted by the introduction of telemedicine to guide future studies, inform health policies, and increase public awareness.",,-99,Dalhousie University (Nova Scotia),13021.09,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P25998,468865,Identifying a path forward to measure racism as a determinant of health within BC population health and wellness reporting,"Evidence from around the world tells us that experiencing racism is bad for your health. Reports from other areas show that COVID-19 and the pandemic response impacted some Indigenous and racialized peoples and communities differently than white people and predominantly white communities. We expect that the same is true in BC, but because we don't collect information about racism as part of our usual health monitoring, we don't know. Right now, BC public health leaders don't have the information they need to make evidence-informed decisions and policies to respond to the impacts of racism on health. It is critical to collect and use this information in a way that makes sense to Indigenous and racialized communities. Our project will begin by looking at what is working or not working in other places. Next, we will bring together leaders from racialized and Indigenous communities, leaders from public health, and university researchers to discuss the best way forward to start to measure racism as part of our province-wide health monitoring. By the end of the project, we want to have a clearer idea of how to move forward in a safe and meaningful way. Our team is well positioned to undertake this work - and put what we learn into action across BC. We are team of Indigenous, racialized, and white public health decision makers, thought leaders and scholars. We will connect with our networks of Indigenous rightsholders and BIPOC community leaders to inform every aspect of our work. Our team includes representatives from the Provincial Health Officer and other members of the Office of the Provincial Health Officer, the BC Centre for Disease Control, Fraser Health Authority, Vancouver Island Health Authority, Black Physicians of BC, University of British Columbia, Simon Fraser University, and University of Victoria.",,-99,University of British Columbia,78307.63,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P26000,454057,Improving Infectious Disease Innovation Governance,"Although the threat posed by coronaviruses has been known for a long time, the world was ill-prepared for Covid19. Prior to the pandemic significant amounts of funding had been allocated to research related to coronaviruses. But progress toward a drug therapy or vaccine was limited before the pandemic began because the systems we rely upon to encourage innovation are tied closely to financial rewards. Unless the financial rewards are predictable, in other words, the interest in developing a drug or vaccine to address an infectious disease like Covid19 will be weak outside of a public health emergency. To improve the world's preparedness against infectious diseases, we therefore need to rethink how we develop drugs and vaccines-we need to change the laws, policies, and practices that we use to drive innovation in order to make the world less vulnerable to future public health emergencies. And we also need to ensure that there are no barriers to sharing knowledge and producing an important intervention like a vaccine in quantities sufficient to meet the world's needs when an infectious disease outbreak occurs. Building upon ten years of research about important public health interventions like the Ebola vaccine that was developed in a Canadian government laboratory, as a Chair in Applied Public Health my goal is to improve the system of infectious disease innovation. I will study how drug and vaccine innovations are developed in the real world, identify practical solutions that can sustain infectious disease research outside of outbreaks, and train the next generation of infectious disease scientists to ensure that their research improves our security and remains broadly accessible to people who are in need, both within Canada and beyond its borders.",,-99,"Health Law Institute, Dalhousie University",906876.09,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Policies for public health, disease control & community resilience",,2021 +P26001,467182,Understanding the Management and Coping of Racial and Ethnic Minoritized Groups with Cardiovascular Disease and COVID-induced Cardiovascular Sequelae,"Numerous short- and long-term implications have been reported in survivors of Coronavirus 2019 Disease (COVID-19). Many patients with COVID-19 may have had heart disease related conditions or may have developed heart related conditions in the course of their COVID-19 illness. Heart disease is a leading cause of death that is known to impact men from minoritized ethnic and racial groups more than other groups. The pandemic had social and economic implications which may have worsened management of heart disease. Therefore the aim of this research is to evaluate the state of heart disease management and coping in individuals from ethnic and racial groups who may have previously had heart disease or may have acquired a heart related condition from contracting COVID-19. Patients will be recruited from follow up clinics in local general hospitals and asked to fill questionnaires pertaining to their heart disease knowledge, coping, and management of their condition and perceived availability of resources and monitoring for their illness at different predetermined time points while visiting the clinics. Overall findings will be summarized and compared between the individuals with previous heart disease and those with COVID induced heart conditions. Findings from this research will inform recommendations for psychosocial and behavioural medicine interventions and monitoring of heart disease patients in the years to come.",,-99,University of Calgary,13724.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Minority communities unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26002,459210,CANCOV2.0: 2-year follow up of the Canadian COVID-19 Prospective Cohort Study,"The post COVID-19 condition represents one of the most important lasting legacies of the COVID-19 pandemic. COVID-19 has infected >1.5 million Canadians and resulted in >27,000 deaths since January 2020. As the world anticipates the second anniversary of this pandemic, there is an urgency to address the legacy of illness from the post COVID-19 condition. Emerging international outcomes data demonstrates a high prevalence of persistent symptoms and varied constellations of clinical features comprising the heterogeneous, and still poorly understood, post COVID-19 condition. The CIHR-funded Canadian COVID-19 Prospective Cohort Study (CANCOV) was designed to provide systematic and in-depth evaluation of 1-year outcomes of patients with COVID-19 across a gradient of illness severity and their family caregivers while exploring novel linkages among granular clinical data, innate genetic susceptibilities and varied host immune responses. To date, CANCOV has recruited 1572 participants (including 567 non-hospitalized ; 529 hospitalized (hospitalized non-ICU: 268 patients and 10 caregivers; hospitalized ICU: 261 patients and 56 caregivers) lab-confirmed patients (and another 410 presumptive COVID cases) and 66 family caregivers from Quebec, Ontario, Alberta and British Columbia. CANCOV 2.0 will refine and disseminate the framework for rapid knowledge to action (K2A) cycles derived from the 1-year CANCOV dataset with an extension to 2-year follow-up and with a specific focus on vulnerable populations. This program will inform how longer-term disability relates to symptoms in the post COVID-19 condition. Further, it will highlight potentially modifiable outcomes for vulnerable Canadians who contracted COVID-19 by informing risk profiles for longer-term clinical and resource use trajectories to better advance planning by health service providers and policy makers.",,-99,University Health Network (Toronto),394293.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26003,468168,Capitalising on our differences: A gathering to better understand and advocate for Early Career Health Researchers in Canada,"Early career health researchers (ECHRS), that is, those in the first seven years of their first research and/or teaching job, make important contributions to research in Canada. The Association of Canadian Early Career Health Researchers (ACEHCR) exists to advocate for and support the interests of ECHRs working in Canada. In order to best plan for the future of health research in Canada, we need to know more about the experiences and career satisfaction of ECHRs in Canada; this is especially important because the impacts of the COVID-19 pandemic have made existing problems in research settings, such as high costs of materials for laboratory experiments, even worse. The ACEHCR will be distributing a survey to as many Canadian ECHRs as possible to learn more about them and the impact of the COVID-19 pandemic on their productivity, job security and job satisfaction. All eleven members of the committee overseeing ACEHCR, who represent different types of research institutions across Canada, have planned an event in Ottawa in the summer of 2023. At this event, committee members will write one or more scientific papers to share the results of this survey. They will also write a document describing the most important findings and recommendations designed to be shared with officials making decisions about policies and programs that most impact ECHRs. Last, committee members will receive training from qualified experts in public relations, strategic communication and effective advocacy. The products of this event will have long-lasting positive impacts, such as improving the sustainability of academic institutions in Canada and optimizing the health of Canadians through effective creation and application of research findings across health care settings.",,-99,University of Prince Edward Island (Charlottetown),7751.3,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Health service delivery | Health workforce,2022 +P26005,469018,Respiratory virus vaccination as public health strategy to protect against occurrence of acute stroke and myocardial infarction,"While studies have clearly shown that vaccinations against respiratory viruses like COVID-19 and influenza prevent pneumonia and death, whether they also prevent heart attacks, strokes, or cardiovascular deaths is unknown. If routine vaccinations help prevent stroke and heart attack, then vaccination would be another approach to preventing these major killers in Canada. Although we have a number of other therapies that prevent these events (aspirin, lipid lowering drugs, blood pressure lowering drugs, etc.), their effectiveness depends on whether individuals take their medications every day or not. A key advantage of vaccinations is that they are given once per year (eg. influenza vaccine) or even once per lifetime (eg. pnemovax). A way in which vaccinations may prevent heart attacks and strokes is that influenza infection can be a trigger for heart attacks and stroke. Vaccination against influenza is known to reduce the occurrence of heart attack in the elderly and those with other concurrent illnesses. We propose to assess the indirect effects of vaccinations for influenza and other respiratory illnesses on the occurrence of acute stroke, acute heart attack and death (both cardiovascular and all-cause). We will assess each of these outcomes individually and together as a composite.",,-99,University of Calgary,91994.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease pathogenesis | Post acute and long term health consequences | Indirect health impacts,2022 +P26006,480723,Assessment of Autonomic Nervous System Function in Post-Acute Sequelae of COVID-19 (PASC) and Characterization of the Patient Experience,"By attending the 2023 American Physiology Summit/Conference, I have the opportunity to share my research findings on Post-Acute Sequelae of COVID-19 (PASC) aka Long-COVID, which is characterized by symptoms lasting >3 months after an initial COVID-19 infection. Sharing these findings with other researchers and physicians allows dissemination of knowledge among professionals with the capacity to develop integrative treatment strategies. This aligns with the Institute's mandate to maximize the impact of new and existing knowledge created by and for the ICRH research community.",,-99,University of Calgary,1107.9,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2023 +P26007,448831,"Identifying and Responding to Person and Facility-Level Determinants of COVID-19 Outbreaks, Mortality, and Adverse Quality of Life Outcomes in Long-term Care","The most severe impact of COVID-19 in Canada has been experienced by long-term care home residents. About three quarters of all Canadian deaths to date have been in this population. This has led to forceful calls to action from many quarters, but limited evidence about the underlying causes of outbreaks and deaths has hindered efforts to better protect this vulnerable population. Vaccination is beginning to reduce COVID-19 mortality and outbreaks in Canadian long-term care, but vaccination rates of residents and staff have not (and may not) reached 100 percent levels. More outbreaks and deaths are possible even if most residents are vaccinated. Also, we must learn all we can from this pandemic to better prepare for future events like this. Several factors make it challenging to understand and respond to COVID-19 in long-term care. The magnitude and severity of outbreaks and deaths varied by region and country. Also, COVID-19 has been a protracted pandemic with multiple waves and seasonal variations in outbreak patterns. Finally, there is preliminary evidence about COVID-19 deaths in long-term care, but almost none related to morbidity, disability, and quality of life. We will use 7+ million assessment records for about 1 million unique individuals in long-term care combined with facility records on staffing, absenteeism, infection control, ownership, and local outbreak patterns to identify the factors that led to outbreaks, widespread infections, deaths, and adverse quality of life outcomes. We will partner with international researchers to do comparable studies in other countries. We will also engage Canadian and international experts, long-term care residents, and family members to review evidence from this research to develop recommendations for changes to clinical practice, service delivery, and policy for long-term care that will better equip this sector to protect the well-being of vulnerable persons in future pandemics or localized outbreaks.",,-99,University of Waterloo (Ontario),286227.35,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Secondary impacts of disease, response & control measures | Health Systems Research","Disease surveillance & mapping | Prognostic factors for disease severity | Supportive care, processes of care and management | IPC in health care settings | Indirect health impacts | Health service delivery",2021 +P26009,469359,Bitter taste receptors and COVID-19,"COVID-19 has affected nearly 4 million Canadians. Some people infected with COVID-19 have very mild symptoms, others have much more severe symptoms and some people even die from COVID-19 infection. Older adults are at particularly high risk of having severe COVID-19 infection. For viruses that are spread through the air like the COVID-19 virus, the immune system in the mouth and lungs is critical to preventing severe disease. We think differences in how well the immune system attacks this new virus may partly explain why COVID-19 infection is different in different people. Some proteins that help taste bitter foods (bitter taste receptors or T2Rs) also play an important role in the body's earliest immune responses to virus infection. This system acts very fast and may stop the virus from attaching to the mouth and nose and may stop the virus from growing. T2Rs are also found on immune cells that make antibodies after COVID-19 infection (or vaccination). Differences in the genes for T2Rs affect how well they work and we think different T2R genes will also affect COVID-19 infection and maybe responses to vaccines. Some studies suggest gene differences in one T2R may affect COVID-19 outcomes. There is no data for other T2R genes, or for T2Rs and vaccines. Methods: We will test whether there are differences in T2R genes between older adults who 1) do or do not get COVID-19 infection and who have mild or severe COVID-19 infection; 2) who do or do not make antibodies after COVID-19 infection or vaccines; 3) who have other medical conditions affecting the risk of severe infections; and 4) we will test several T2R genes. Impact: This information will tell us more about how the immune system in older adults responds to viral infections and vaccines and possibly how to predict who is at greater risk of severe infections. This will help older adults, their care-givers, and policy makers make informed decisions about preventing and managing infections.",,-99,University of Manitoba,53663.44,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease susceptibility | Characterisation of vaccine-induced immunity,2022 +P26011,459276,COVID-19 and the Care of Assisted living Residents in Alberta (COVCARES-AB),"COVID-19 has had a devastating impact on older adults living in long-term care (LTC) & assisted living (AL). Residents in these settings experienced higher rates of COVID-19 infection and more serious outcomes than those in the community. Most media and research attention has focused on LTC, largely neglecting AL. AL residents are similar to those in LTC, and AL faces the same concerns as LTC about staffing, oversight, and infection prevention. However, AL provides fewer services and lower staffing levels than LTC. Yet, the immediate and longer-term effects of COVID-19 on AL residents remain poorly examined in Canada - and especially in Alberta, whose AL system (called Designated Supportive Living; DSL) is unique in the country. Our aim is to understand how COVID-19 and facility policies have impacted DSL & LTC residents' physical and mental health, quality of care, and health services use, and how these impacts have changed over time. We will conduct a population-based, observational study, using clinical and health administrative data for all DSL & LTC residents in Alberta between 01/2017 and 12/2021. We also have rich, unique survey data collected from 64 DSL homes and 35 LTC homes in Alberta, assessing preparedness for the pandemic, measures implemented, challenges encountered and interactions with residents' family/friend care partners. We will link these facility surveys to residents' clinical and health administrative data to assess how facility characteristics are associated with resident outcomes. This study addresses an urgent, critical need to better understand the impact of COVID-19 on a growing but under-researched care setting for older Canadians. Understanding how effects of COVID-19 on AL/DSL residents changed over time will lead to improvements in policies and practices related to family and resident communication, AL/DSL staffing and services, and balancing infection control measures with maintaining the health and well-being of DSL/AL residents.",,-99,University of Alberta,192896.49,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26012,448917,Implementing the Provincial Post COVID-19 Rehabilitation Framework for Screening & Transitions in Alberta: A Pragmatic Evaluation,"Post COVID-19 Syndrome affects about one in ten COVID-19 positive patients and is characterized by complex and chronic symptoms (e.g. fatigue, shortness of breath, limited activity tolerance, anxiety and cognitive problems) after the initial diagnosis. These can continue for months and can have a lasting, detrimental impact on patient health and quality of life. Rehabilitation can help relieve these symptoms. In March 2021, Alberta Health Services, a provincial health system, released the Provincial Post COVID-19 Rehabilitation Framework (PCRF) to support patients with Post COVID-19 Syndrome. It is based on international recommendations, consensus and co-design with patients, family, clinicians, administrators, and researchers. It includes care pathways, symptom screening and functional assessment tools, as well as education and self-management resources for patients, caregivers and clinicians, in order to address patient-specific post COVID-19 rehabilitation needs across the care continuum. A critical next step is to implement the PCRF across Alberta. This study aims to explore the impact of PCRF implementation on adult patients hospitalized with COVID-19 who transition home. We will study: (i) the impact of PCRF implementation on health system resource utilization; (ii) the patient and healthcare provider experiences before and after PCRF implementation; and (iii) the PCRF implementation strategy in terms of acceptability, adoption, feasibility and fidelity. The study will be done through surveys, focus groups and interviews conducted at many different time points before and after PCRF implementation so we can study its effects. In all analyses, we will look at how geographical location, sex, gender and ethnicity may affect PCRF implementation. The outcomes of this study are expected to support the spread and scale-up of the PCRF in Alberta, informing other health systems' approaches to support the diverse and complex symptoms of Post COVID-19 syndrome.",,-99,University of Alberta,397129.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health service delivery,2021 +P26015,468120,Canadian Developmental Biology Conference,"This meeting is the 11th Canadian Developmental Biology Conference and the 9rd Canada Regional Meeting of the North American Society for Developmental Biology. The meeting has been held once every two years since 2002, with the location alternating between Quebec in the east and Banff in the west of Canada. Due to the large geographic area covered by the Canadian region of the SDB, this meeting is the major opportunity for developmental biologists across Canada to meet to discuss science. From 2002 to 2018, attendance varied between 171 and 265 participants, with about 60% consisting of trainees (students or postdocs). Due to the COVID-19 pandemic, the scheduled 2020 meeting was held entirely virtually in April 2021. Canadian developmental biologists are located in large and medium cities that are dispersed throughout a very wide geographic area. New investigators are extended priority invitations in order to introduce them to the community to facilitate recognition of their work nationally and to those who serve on grant panels. Developmental biologists in relatively small centres who would be isolated within their local environment are also extended invitations to immerse them with the Canadian community. Postdoctoral and graduate trainees are given priority for short talks in order to encourage their interest in the field and strengthen future prospects for developmental biology in Canada. The 3 day program is sub-divided into five sessions, with three to six invited speakers (30-minute talks) per session. Sessions will also include one to three 15-minute talks selected from submitted abstracts with priority given to junior faculty, postdocs and students. Two poster sessions are also planned for afternoons of the 24th and 25th. The program includes an educational session on equity, diversity and inclusion in science and two keynote lectures.",,-99,Hospital for Sick Children (Toronto),11626.95,Not applicable,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P26016,472158,Investigating the impact of distinct pandemic prenatal stressors on early immune disruptions in children via alterations to prenatal inflammatory pathways,"During the COVID-19 pandemic, there was an increase in psychological (e.g., anxiety), environmental (e.g., financial hardship), and viral stress (e.g., SARS-CoV-2 infection). Pregnant individuals were very vulnerable as sustained stress and exposure to infection magnifies the risk of health consequences for the fetus. Our research program examines the impact of viral, psychological, and environmental pandemic-related prenatal stress on indicators of immune disruption in children via alterations to prenatal inflammation. This research leverages the Pregnancy during the Pandemic cohort (a pan-Canadian sample of n>11,000 recruited prior to widely available vaccines [April 2020 -2021]) to investigate the impact of prenatal stress on the following immune-mediated child conditions: asthma, allergic diseases, and inflammatory skin conditions. In the proposed study, we compare the strength of associations between cumulative prenatal stress on child health conditions and the unique relationship of each type of prenatal stress on child health. We hypothesize that viral stress (confirmed via antibody COVID-19 testing) will have the most robust association with medical diagnosis of child health conditions. The second aim will test the degree to which prenatal parent inflammation mediates the association between prenatal stressors and child health conditions; specifically investigating C-reactive protein brain-derived neurotrophic factor levels. Lastly, we will investigate gestational age and fetal sex potential moderators. Prenatal stress has been linked to later-onset health problems. This study will help to disambiguate unique contributions of types of prenatal stress and connect this to early signs of health degradation. The study also considers the mechanistic contributions of parental inflammation on these complex relationships. Ultimately, these results can help inform developing interventions aimed at supporting vulnerable populations during the COVID-19 pandemic.",,-99,University of British Columbia,65793.1,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26018,484182,Efficacy of antioxidant therapy in mild to moderate SARS-CoV-2 infection: An experimental arm of the CanTreatCOVID adaptive platform trial,"While current SARS-CoV-2 outpatient therapies have demonstrated efficacy in lowering hospitalization and death rates, they also come with limitations, including high costs, restricted eligibility, and potential side effects. This highlights the need for alternative and safe therapeutic approaches. Antioxidant therapy offers a promising solution, as it has the potential to provide similar results to current medications without the risk of side effects, and at a lower cost. The Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID) aims to assess the clinical and cost-effectiveness of various treatments for non-hospitalized patients with COVID-19. This study, as part of the CanTreatCOVID, will specifically examine the effectiveness of combined antioxidant therapy (consisting of 300ug selenium, 40mg zinc, 45mg lycopene, and 1.5g vitamin C) for 10 days compared to standard care and other study treatments. Eligible participants are adults (aged 18-49 years with chronic condition(s) or those aged 50+ years), who have tested positive for COVID-19 within 5 days of symptom onset. Participants will be randomly assigned to standard of care, combined antioxidant therapy, or other study interventions. The main outcomes are time to recovery and hospitalization/death at 28 days. This study aims to support the CanTreatCOVID initiative in identifying effective and accessible treatments for COVID. Outpatient treatments for SARS-CoV-2 infection should be safe, easy to administer, widely accessible, and cause minimal side effects. With antioxidants widely available at a fraction of the cost of current COVID-19 treatments and without the need for a prescription or close medical supervision, this alternative therapy has the potential to reach and benefit communities both in Canada and worldwide.",,-99,Unity Health Toronto,73535.55,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments,2023 +P26019,494308,Adaptive platform trials in pandemics: Evaluating COVID-19 case studies and developing guidelines for future health emergencies,"COVID-19 quickly became a global health issue, and we needed fast and effective ways to study potential treatments. While traditional clinical trials are reliable, they can sometimes be slow and costly. A newer approach called Adaptive Platform Trial (APT) is more flexible and can respond faster to new health crises. APTs proved invaluable in speeding up research during urgent times such as the COVID pandemic. In this study, we will be closely evaluating three specific APTs related to COVID-19: TOGETHER, PANORAMIC, and REMAP-CAP. Our main goal is to understand how these studies were designed, how they operated, and the results they achieved, all amidst the challenges of the pandemic. We're particularly interested in their innovative techniques and what proved successful or problematic. From what we learn in this first step, we will then draft a set of guidelines. These guidelines will help us set up and run similar trials quicker and more efficiently in the future, whether for other diseases or another pandemic. By doing so, we aim to ensure Canada is better prepared and can respond more rapidly in future health crises, leading to improved patient outcomes.",,-99,Unity Health Toronto,73558.84,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Therapeutic trial design | Vaccine trial design and infrastructure,2023 +P26027,432529,Promising Practices in Accessing Virtual Mental Health: Supporting Refugees during COVID-19,"The goal of this project is to identify key concerns and promising practices with respect to delivery of virtual mental health services, and to develop guidelines for referring refugee clients to these services. The COVID pandemic can affect immigrant and refugee mental health in multiple ways: 1) anxiety about the illness itself; 2) challenges due public health measures, including social isolation, and one's ability to enact these measures; 3) economic stress due to loss or reduction of employment; and 4) decreased or altered access to mental health treatments and medications for those already receiving services. While many on-line mental health services have become available or expanded services, new questions are arising in the settlement sector around access and barriers to these services and considerations when referring. Immigrants may find access to linguistically and culturally appropriate virtual mental health services difficult to find and navigate. Refugees may face even greater barriers relative to other immigrants. Vulnerable populations such as refugees are more likely to be living in crowded conditions that can make physical distancing difficult and may have greater difficulty accessing or understanding public health directives; they are more likely to be experiencing economic hardship; and they may be less likely to have access to or be comfortable using virtual technologies. Through interviews with settlement workers, refugee newcomers, mental health practitioners and virtual mental health experts, we will develop guidelines around WHEN to refer WHICH clients to WHICH virtual mental health services; HOW to refer and document virtual mental health services; and WHAT are key considerations in referring and recommending virtual mental health services to refugee clients. Although developed for refugees, these recommendations will highlight barriers faced by many vulnerable populations and sharing promising practices will support better access for all.",,-99,"York University (Toronto, Ontario)",115702.96,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26031,462705,Aki Gimiinigonaa Mshkooziiwin (The Land Gives Us Strength): Culturally-grounded healing within the urban-Indigenous community during COVID-19,"Aki Gimiinigonaa Mshkooziiwin (The Land Gives Us Strength): Culturally-grounded healing within the urban-Indigenous community during COVID-19 is an urban Indigenous community-led knowledge mobilization project. The Cost of COVID study was a prior research collaboration that looked at social and emotional impacts of the COVID pandemic among urban Indigenous community members around Kingston, ON. Study findings emphasized that reclaiming food systems and moving toward Indigenous food sovereignty (IFS), land access and cultural revitalization will contribute to the overall wellness and sustainable health goals of the urban Indigenous community during COVID and support long-term recovery. The goal of the project is to share and action knowledge from the Cost of COVID study. We will do this by supporting IFS and building skills and awareness around cultural protocols, self-care and well-being. The key objectives are: 1) To develop, implement, and evaluate strengths-based, Indigenous community-led COVID -19 pandemic recovery solutions to increase IFS, food security, and community belonging using land- and language-based activities rooted in Indigenous languages and cultures, and 2) To improve mental health among the Indigenous community during COVID-19 pandemic recovery using culturally grounded, land-based activities. The knowledge mobilization program will include culturally grounded and socially supportive activities: 1) community foraging during forest walks; 2) growing medicines in community gardens and 3) working together to build Personal Bundles. The Indigenous Diabetes Health Circle (IDHC), Queen's University, and the Kingston Indigenous Languages Nest (KILN) have partnered to move the evidence from the Cost of Covid study into practice. They will work collaboratively, along with local urban Indigenous community members, to enhance programming to nurture health and well-being among urban Indigenous people in the current phase of the pandemic and into the future.",,-99,"Indigenous Diabetes Health Circle (Thorold, ON)",102735.79,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Other secondary impacts,2021 +P26034,481133,Optimizing Mpox surveillance strategies and preventing epidemic resurgence: a three-province mathematical modeling study,"Mpox is a viral disease that causes blisters and lesions on the body. It is generally transmitted from animals to humans but, during the 2022 global outbreak, human-to-human transmission was sustained through sexual contacts. The outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM) in Canada's three largest cities. Following a rapid public health response, it was brought under control in Canada. The mpox virus isn't completely gone, however, and we are not indefinitely protected from epidemic resurgence. With potential for mpox resurgence, public health authorities will need guidance to identify and define new outbreaks that could lead to significant transmission. Conditions that would facilitate new epidemics include sub-optimal vaccine coverage, loss of immunity, and changes in sexual networks. Wastewater-based surveillance (WBS) could be used to detect mpox and track outbreaks but has not been validated yet. Other potential surveillance strategies should consider the overlap between mpox and other sexually transmitted infections. For instance, 3 out of 5 people diagnosed with mpox in Canada had a recent history of sexually transmitted infections. Our project aims to inform national decision-making by answering three questions: 1.If new cases emerge, how will we know if there is about to be another large outbreak versus one that is self-contained? 2.What would it take to stop a new outbreak in its tracks, given the current coverage of vaccinations and infection-derived immunity? 3.Which surveillance strategies need to be put in place to detect new cases early and efficiently? To fill these knowledge gaps, our interdisciplinary team of trainees, epidemiologists, modelers, clinicians, engineers, microbiologists, health economists, public health professionals, and community-based researchers will help our country prepare for and respond to future infectious threats.",,-99,B.C. Centre for Disease Control (Vancouver),375198.56,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Epidemiological studies | Policies for public health, disease control & community resilience",Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes | Ongoing assessment & evaluation of surveillance | Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts | Evaluation of elimination strategy implementation in different contexts.,Canada,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Policy research and interventions,2023 +P26037,449325,'Living' systematic review on thoracic imaging for the diagnosis of coronavirus disease 2019 (COVID-19),"People that are suspected of having coronavirus disease 2019 (COVID-19) need accurate diagnostic tests to determine whether they are infected, so they can receive treatment & self-isolate to prevent the spread of infection. The current standard for diagnosing COVID-19 are reverse transcriptase polymerase chain reaction (RT-PCR) tests. However, RT-PCR tests are not always accurate in diagnosing COVID-19 & are not always available for reasons such as test backlogs. In these situations, alternative diagnostic methods may be necessary. Our aim is to assess the accuracy of chest imaging tests in diagnosing COVID-19. This is an ongoing project part of the Cochrane Series of 'Living' Systematic Reviews for the Diagnosis of COVID-19 (baseline review published in September 2020). We will continue to update this review every three months over the next two years to incorporate new evidence as it becomes available. We will search for studies that evaluate the accuracy of chest imaging tests (chest X-ray, chest computed tomography (CT) & ultrasound of the lungs) in diagnosing COVID-19 in people suspected of having the disease. For each type of imaging test, we will pool & analyze the accuracy results. In the most recent update of this review, we found that chest CT imaging tests correctly diagnosed COVID-19 in 90% of people with the disease & incorrectly diagnosed COVID-19 in 39% of people without the disease. These results showed a higher accuracy of chest CT imaging tests compared to the results of our baseline review. As we continue to compile more evidence, we will aim to improve the precision of our current results, determine the accuracy of chest X-ray & ultrasound & evaluate secondary objectives such as the association between symptom severity & chest imaging findings.",,-99,University of Ottawa,13459.8,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2020 +P26038,449941,"""Living"" systematic review on thoracic imaging for diagnosis of coronavirus disease 2019 ( COVID-19)",N/A,,-99,University of Birmingham (U.K.),4963.24,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P26041,460278,A narrative inquiry study into the impacts of the COVID-19 pandemic on the experiences of children and youth waiting for mental health services,"The mental health of children and youth in Canada has been greatly impacted by the COVID-19 pandemic. The COVID-19 pandemic worsens existing mental health symptoms among children and youth as well as leads to new mental health issues due to prolonged isolation, illness in the home, fear of infection, school closure, familial financial loss, disruption of routine, and uncertainty of the future. Children and youth may also be affected by exposure to domestic violence, child maltreatment, lack of free school meals, decreased access to social and academic school supports, housing and overcrowding concerns, and a significant change to social networks. Public health restrictions have erased access and involvement with community activities and adult supports outside of the home that often serve as protective factors and help young people to cope with mental health issues. Unfortunately, COVID-19 has worsened the urgent need for child and youth mental health services that already existed in Canada before the pandemic. The results of ""waiting"" for care and treatment can be devastating resulting in early school leaving, involvement with the youth justice system, bullying, trauma, substance use, economic burdens and suicide. This research study will explore 1) the experiences of children and youth who are waiting for mental health services during the COVID-19 pandemic; 2) identify resources, strategies and supports used by children and youth while waiting for mental health services during the COVID-19 pandemic; 3) strengthen the current child an youth mental health care system in Canada though providing knowledge of innovative resources, strategies and supports for children and youth that can be utilized to help children/youth while the wait for formalized mental health mental health treatment during and after the COVID-19 pandemic.",,-99,MacEwan University (Edmonton),231954.75,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26046,480228,Pre-clinical development of a novel class of broad-spectrum natural product antivirals,"Emerging human viruses such as SARS-CoV-2 (cause of COVID-19), influenza A virus (acute respiratory infection), and Zika virus (microcephaly and other congenital malformations), have had an enormous impact on human health. The World Health Organization (WHO) has declared these three to be Public Health Emergencies of International Concern (PHEICs). Although vaccines have greatly limited COVID-19 and Influenza-related hospitalizations and deaths, these viruses are continually changing, rendering vaccines less effective over time. What's more, no vaccine is available yet for preventing Zika virus infection. Importantly, no broad-spectrum antiviral drugs are available against these three viruses despite the fact that each virus was declared a PHEIC [influenza A pandemic (2009); Zika virus epidemic (2016); COVID-19 pandemic (2019)]. Our research team has discovered an exciting drug that can block infections in human cells caused by SARS-CoV-2, influenza A, and Zika, which we call a broadly acting antiviral. The drug, called cladoniamide A (CA), is a natural product (NP) discovered in British Columbia that blocks a human protein complex called vacuolar ATPase that helps human viruses get into our cells. NPs as drugs have fewer side effects and a faster approval process than chemically engineered drugs, a great advantage in dealing with a pandemic. In this research proposal, we plan to further improve the pharmaceutical and antiviral properties of CA and develop a new class of nature-based broad-spectrum medicines against SARS-CoV-2, influenza A, and Zika viruses. We anticipate that this research will further develop cladoniamide A and its derivatives so they can be further tested in clinical trials. In the future, this will lead to new and exciting broad-spectrum possibilities for treating other human viral diseases of global health concern.",,-99,University of British Columbia,579423.37,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Zika virus disease | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P26048,477310,"Developing and Assessing Feasibility, Acceptability, and Perceived Impact of the Enabling Sustainable and SafE health care through fundamental Nursing CarE in Canada: The ESSENCE CANADA STUDY","As part of recovery efforts from the pandemic and ongoing human health resource (HHR) challenges, a focus on retaining nurses and enhancing their ability to provide quality patient care is paramount as they represent the largest workforce providing patient care globally. There is an urgent need for leaders to influence a humane, compassionate evidence-informed approach to managing and recovering from the COVID-19 pandemic by focusing on restoring fundamental care as part of their organizational mandate and daily care practices.We need to address the current quality gaps in fundamental care, strengthening the nursing profession by developing, assessing the feasibility, acceptability, and perceived impact of strategies aimed at recovering from the COVID-19 pandemic, and reducing missed care. Following this initial intervention development phase, we plan to undertake a multi-site, sectoral intervention trial across Canada as part of a larger global networked research program.",,-99,Sinai Health System (Toronto),73103.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery | Health workforce,2022 +P26052,466539,Prenatal stress and subsequent maternal pain associated with altered brain development in children,"Chronic pain is a major public health issue, affecting one in five Canadians. The estimated costs of chronic pain in Canada are $60 billion CAD per year. Chronic pain impacts social, emotional, and daily functioning. However, every case of chronic pain starts as acute pain. Early detection and pain management may prevent the transition from acute to chronic pain.Research suggests that anxiety disorders may increase the risk of developing chronic pain. Public health measures put in place to stop the spread of COVID-19 have increased rates of anxiety, notably in pregnant individuals. Pregnant women currently have three to four times higher levels of anxiety than they did prior to the pandemic. Pandemic-related anxiety may increase the risk of pregnant women developing chronic pain. There is also an increased risk of prenatal stress to the developing brains of infants. Animal studies have shown that prenatal stress is related to altered brain development, increased pain sensitivity, and anxious behaviors in offspring. Moreover, both prenatal stress and maternal physical symptoms, such as pain, are linked to increased pain symptoms in children at 18 months of age. However, little is known about the relationships between prenatal stress and maternal pain, and whether it alters child brain development, thereby contributing to emotional, and pain sensitivities in children.This project will leverage longitudinal data collected from 10,000+ mothers across Canada to explore the relationships between prenatal stress, maternal pain, and child brain development. Identifying factors contributing to the development of chronic pain will lead to earlier intervention strategies to reduce the prevalence, costs and life-long suffering of chronic pain for Canadians and their families.",,-99,University of Calgary,13724.56,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26053,459214,Ab-C Risk: Action to Beat Coronavirus Sub-study on Population Immunity in High-Risk Groups in Canada,"We have been studying the impact of SARS-CoV-2 infection and vaccination on immunity among a representative sample of about 20,000 Canadian adults, in the Action to Beat Coronavirus in Canada (Ab-C) study, since early in the pandemic. Ab-C Risk will recruit an additional 1,000 Canadians belonging to higher risk demographic and ethnic groups. The Ab-C cohort was recruited in collaboration with the Angus Reid Institute, which will continue to lead in surveying participants periodically about COVID-related experiences, including infection, clinical signs and symptoms, exposures, PCR testing for the virus (including variants of concern), and vaccination. Ab-C relies on participants to self-collect finger prick blood samples on special paper, and send them to Unity Health for analysis for SARS-CoV-2 antibodies. Three rounds of surveys and blood samples have been completed. A fourth and fifth round, planned into 2022, will include the new Ab-C Risk cohort. The main Ab-C Risk research questions are: 1. What are the levels of SARS-CoV-2 vaccine-induced and natural immunity among VIPs compared with other groups? 2. How does persistence of SARS-CoV-2 antibodies among VIPs compare with other groups? 3. Can we identify age-specific predictors of maintained and declining SARS-CoV-2 antibodies among VIPs compared with others? After each Phase, Ab-C publishes for a professional audience in high-impact journals, and for the public in a variety of forms, including Ab-C newsletters and interviews with the Canadian press. We plan to add video releases to be widely distributed to planners and others working with VIPs. The Ab-C team, from six Canadian research institutions and the Angus Reid Institute, combines experience in large-scale population epidemiology, demography and biostatistics, laboratory science, clinical infectious disease, Indigenous health, health economics and priority setting, health equity, IT, communications, and knowledge translation.",,-99,Unity Health Toronto,393743.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P26055,486421,The role of pandemic income supplementation on the prevalence of food insecurity in Canada and the impact on the social gradient of food insecurity.,"Food insecurity remains a large issue across Canada, particularly among the working poor. Those most at risk for food insecurity are those receiving forms of income supplements. Income supplementation involves the transfer of cash to workers who do not make enough to surpass the poverty threshold, despite in some cases working full time. Although the pandemic led to the temporary loss of many jobs in low-wage sectors, food insecurity rates decreased. Income supplementation during COVID-19 in the form of CERB and other related programs may provide insights as to why food insecurity rates declined when they may have otherwise been expected to rise. This research will investigate the impact that income supplementation had on the prevalence and severity of food insecurity in the first year of the pandemic using linked data from the Canadian Income Survey and pandemic income supplementation programs recipient data. This project would show how income supplementation on a mass scale impacts food insecurity levels, helping direct future policies directed towards the elimination of food insecurity in Canada and could provide support for the implementation of a universal basic income system to reduce the impacts of poverty.",,-99,Dalhousie University (Nova Scotia),13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2022 +P26063,486275,Investigating the role of ORF6 and NSP13 interactions with Cdk5rap2 in SARS-CoV-2 pathogenesis,"The continuing COVID-19 pandemic represents one of the most extreme health and economic crises in human history. Excessive release of proinflammatory cytokines, termed 'cytokine storm', is the underlying cause of COVID-19 clinical manifestations. Recently, it was shown that out of 31 proteins produced by the COVID-19 virus, 4 nonstructural (NSP8, 9, 13 & 16), and 3 accessory (ORF3b, 6 & 9b) proteins interact with cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2). However, the consequence of these interactions during COVID-19 pathogenesis remains unknown. Interestingly, our laboratory has demonstrated that Cdk5rap2 loss (i) induces cell senescence that accompanies the secretion of high levels of inflammatory cytokines and (ii) stimulates phosphodiesterase 4D (Pde4d), reducing intracellular cAMP concentration, which up- and down-regulates pro- and anti-inflammatory cytokine production, respectively. Since NSP13 and ORF6 of the 7 Cdk5rap2-interacting COVID-19 proteins kills human cells by 30% and 50%, respectively, my HYPOTHESIS is that Cdk5rap2-NSP13/ORF6 interactions stimulate Pde4d, subsequently causing a cytokine storm. I will employ our laboratory's expertise in cell and molecular biological approaches to address my OBJECTIVE to elucidate the role of ORF6 and NSP13 interactions with Cdk5rap2 in COVID-19 pathogenesis. My SPECIFIC AIMS are (i) to investigate whether ORF6 and NSP13 stimulate Pde4d activity via Cdk5rap2 binding and cause downregulation of intracellular cAMP concentration, and (ii) subsequently increase pro-inflammatory cytokine secretion while decreasing anti-inflammatory cytokine release. Results from my studies could provide novel insight into therapeutic strategies to effectively combat COVID-19 infections.",,-99,University of Calgary,13021.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P26066,445322,Avoiding pitfalls in virtual care: paving the road for more ethical and equitable policies and practices in rehabilitation,"Telerehabilitation use, or virtual rehabilitation, has grown exponentially in order to continue to provide essential rehabilitation services to the population during the Covid-19 pandemic in response to physical distancing requirements. However, clinicians who provide virtual rehabilitation services have had inconsistent and incomplete guidance for this new way of offering services, which can affect the quality of care for the most vulnerable among our society. Managers and decision-makers are also faced with difficult choices when choosing to put in place virtual rehabilitation. As well, people with disability need to be better equipped to this new way of receiving rehabilitation services. As a team of researchers with multiple partners in the community and health care sectors, we aim to put in place a community of practice that will learn from research and current virtual rehabilitation practices, and work together to share, support and improve the use of virutal rehabilitation in Canada. We will conduct a review of the virtual rehabilitation literature, analyze current virutal rehabilitation practices, and examine clinicians, managers, decision makers, and people with disability's experiences with virtual rehabilitation to better understand what works, what does not, and why. We will hold consensus meetings to create and contribute to guiding principles and tools for the continued use of virtual rehabilitation activities to ultimately improve the health and wellbeing of all people with disability.",,-99,Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal,291720.14,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Health Personnel | Hospital personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2021 +P26067,448403,Avoiding pitfalls in virtual care: paving the road for more ethical and equitable policies and practices in rehabilitation,"Telerehabilitation use, or virtual rehabilitation, has grown exponentially in order to continue to provide essential rehabilitation services to the population during the Covid-19 pandemic in response to physical distancing requirements. However, clinicians who provide virtual rehabilitation services have had inconsistent and incomplete guidance for this new way of offering services, which can affect the quality of care for the most vulnerable among our society. Managers and decision-makers are also faced with difficult choices when choosing to put in place virtual rehabilitation. As well, people with disability need to be better equipped to this new way of receiving rehabilitation services. As a team of researchers with multiple partners in the community and health care sectors, we aim to put in place a community of practice that will learn from research and current virtual rehabilitation practices, and work together to share, support and improve the use of virutal rehabilitation in Canada. We will conduct a review of the virtual rehabilitation literature, analyze current virutal rehabilitation practices, and examine clinicians, managers, decision makers, and people with disability's experiences with virtual rehabilitation to better understand what works, what does not, and why. We will hold consensus meetings to create and contribute to guiding principles and tools for the continued use of virtual rehabilitation activities to ultimately improve the health and wellbeing of all people with disability.",,-99,Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal,59583.36,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Health Personnel | Hospital personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2021 +P26068,460251,COVID-19 pandemic effects on outcomes of patients in a provincial home ventilation program,"Patients requiring long-term home non-invasive ventilation are a diverse group with different diagnoses leading to chronic respiratory failure. They are amongst the most vulnerable patients requiring home care due to their severe respiratory impairment. The Quebec National Program for Home Ventilatory Assistance (NPHVA) is a province-wide publicly funded program proving ventilators/BPAP machines and home respiratory care through Respiratory Therapists (RTs). Our aims are to 1)Determine the impact of the pandemic on care of NPHVA patients, by calculating hospitalizations and mortality during the pandemic compared to prior to the pandemic, by determining usage of ventilators/BPAP devices, and by comparing the number of monthly referrals to the program during the pandemic with that in the 2 years prior to the pandemic. We will look at whether there are differences in above measures based on: diagnostic category; gender; age categories (children, young to middle-aged adult, elderly); type of residence (long-term care, home); location of residence (urban, rural). 2) Understand the perception NPHVA patients have of the care they received during the pandemic, as individuals requiring a respiratory device. We want to understand challenges and facilitators of self-management in the pandemic. We will also study caregivers. Finally, we will ask RTs and doctors looking after these individuals about their perception of care of patients in the NPHVA. Data will be obtained from NPHVA records, from provincial databases and from questionnaires and interviews. This study will help us understand how the COVID-19 pandemic has impacted provision of care in vulnerable individuals with chronic respiratory failure who depend on home care. With clearer data, we will be in a better position to identify potential targets for intervention to minimize impacts of any future waves of COVID-19, other pandemic or other major care disruptors.",,-99,Research Institute of the McGill University Health Centre,356924.95,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Rural Population/Setting | Urban Population/Setting,Other,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +P26071,494255,Inflammatory Bowel Disease in 2035: A National Study of the Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC),"Approximately 0.8% of Canadians are living with inflammatory bowel disease (IBD), which consists of Crohn's disease and ulcerative colitis-more than 322,000 Canadians in total, and that number is quickly increasing. Soon, more than one out of every 100 Canadians will be living with IBD. In Canada, IBD costs the healthcare system over $3 billion per year. Because ulcerative colitis and Crohn's disease are chronic, incurable diseases typically emerging during youth, the number of people afflicted by IBD continues to steadily rise in Canada. The goal of the proposed project is to prepare Canada's healthcare system to meet the challenges that people with IBD and society will face over the next decade from the rising burden of IBD: Soaring costs, more complicated healthcare needs due to coexisting medical conditions, and an ever-growing number of people needing care. We address this challenge by building statistical models, which account for the influence of the COVID-19 pandemic and forecast the future needs to care for the IBD community. This research facilitates implementing innovations in healthcare delivery to improve the quality of care for people with IBD. This research program is a partnership with Crohn's and Colitis Canada, whose mission is to improve the quality of life for everyone affected by these diseases. Through this partnership and research, we help them move closer to achieving that goal. Critically, our research involves members of the IBD community as patient and caregiver partners in the scientific process so that they can have a say in our research goals, explain what is important to them and how it affects them, and help to identify crucial knowledge gaps and actionable outcomes that Crohn's and Colitis Canada can use to improve the lives of people living with these diseases.",,-99,University of Calgary,73558.84,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26074,446143,The Bhagirath Singh Early Career Prize in Infection and Immunity: Hematopoietic stem cell sequelae in fetuses and offspring exposed to in utero Zika infection,"Zika virus (ZIKV) emerged in the Americas in 2015 and posed ongoing public health concerns. The outcomes of ZIKV infection are fetal death, brain lesions, and life-long impairment in children. Alarmingly, the majority of fetal infections are mild with no easily identifiable birth defects; however, later health complications in initially asymptomatic ZIKV-affected offspring were demonstrated in our animal model studies and studies in humans. It is not known, however, how abnormalities acquired during fetal infection are sustained and endure in offspring. Our preliminary studies suggest that mild ZIKV infection in fetuses causes systemic inflammation deteriorating fetal hematopoietic stem cells (HSCs)-long-living cells that maintain the immune system for the life span. Fetal HSCs affected during a developmental period in the maternal womb may sustain acquired pathology after birth causing long-term HSC abnormalities and enduring dysfunction of immunity in offspring. We will use state-of-the-art molecular techniques and advanced large animal models to understand better how ZIKV affects HSCs and their ability to maintain the immune system. A better understanding of long-term effects caused by mild in utero infection will support the development of therapeutic strategies. Importantly, in addition to ZIKV infection, the new knowledge may be applied to other viruses that are known to cause mild fetal infections. Our studies may help to reduce health sequelae in offspring and treatment required after birth. It will be highly-rewarding for patients, families, and society and will decrease the social and economic burden associated with congenital infections.",,-99,University of Saskatchewan,9338.99,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P26075,433008,Hematopoietic stem cell sequelae in fetuses and offspring exposed to in utero Zika infection,"Zika virus (ZIKV) emerged in the Americas in 2015 and posed ongoing public health concerns. The outcomes of ZIKV infection are fetal death, brain lesions, and life-long impairment in children. Alarmingly, the majority of fetal infections are mild with no easily identifiable birth defects; however, later health complications in initially asymptomatic ZIKV-affected offspring were demonstrated in our animal model studies and studies in humans. It is not known, however, how abnormalities acquired during fetal infection are sustained and endure in offspring. Our preliminary studies suggest that mild ZIKV infection in fetuses causes systemic inflammation deteriorating fetal hematopoietic stem cells (HSCs)-long-living cells that maintain the immune system for the life span. Fetal HSCs affected during a developmental period in the maternal womb may sustain acquired pathology after birth causing long-term HSC abnormalities and enduring dysfunction of immunity in offspring. We will use state-of-the-art molecular techniques and advanced large animal models to understand better how ZIKV affects HSCs and their ability to maintain the immune system. A better understanding of long-term effects caused by mild in utero infection will support the development of therapeutic strategies. Importantly, in addition to ZIKV infection, the new knowledge may be applied to other viruses that are known to cause mild fetal infections. Our studies may help to reduce health sequelae in offspring and treatment required after birth. It will be highly-rewarding for patients, families, and society and will decrease the social and economic burden associated with congenital infections.",,-99,University of Saskatchewan,434375.03,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P26076,448823,Long-term Sequelae of COVID-19: Using Clinical and Administrative Data to Support Diagnosis and Treatment of Long COVID Patients,"""Long COVID"" is the name for COVID-19 illness that lasts more than 4 weeks. Patients with long COVID may have symptoms like shortness of breath or develop life-threatening blood clots that can cause stroke and other organ damage. In this proposal, we aim to describe long COVID patients using health system data to help healthcare providers learn about, diagnose and treat long COVID. Knowing more about how many patients have long COVID and what their risk factors are is also important for planning health system needs and policy. Manitoba has a large, linkable data resource spanning many years that contains information on every person who comes into contact with the Manitoba health system. We will use data from this resource, including hospital admissions data, electronic medical records from doctors' clinics, and data from labs and pharmacies for our study. With the permission of First Nations, we will also access health records from individuals receiving federally funded health services in Manitoba First Nations communities. We will apply sophisticated biostatistical methods to examine patients' characteristics (age, sex, income), other conditions (e.g., cardiovascular disease), geography (urban/rural), First Nations identity, immigrant status, and COVID-19 severity (length of time in hospital or intensive care, drugs prescribed). The analyses will allow us to develop a practical definition of long COVID, and to estimate how likely it is that someone who with COVID-19 later develops long COVID. Our multi-disciplinary team of researchers, clinicians, patients and knowledge users will work together to ensure the findings are relevant to practice and policy and will support clinicians caring for long COVID patients. We will share our analytic approach and findings through existing regional and pan-Canadian networks to build capacity in understanding this evolving condition.",,-99,University of Manitoba,160481.83,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Internally Displaced and Migrants | Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26081,450262,Universal vaccine approaches for current SARS-CoV-2 variants and future coronaviruses in LMICs,"The COVID-19 (coronavirus disease 2019) pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2 or SARS2) has significantly impacted global public health and wellbeing. Newly developed COVID-19 vaccines protect against infection of the original Wuhan SARS2 virus, but SARS2 variants are a real threat to ending the pandemic. Delays and deficits in vaccine procurement and deployment in low- and middle-income countries (LMICs) are more exacerbated with the emergence of new variants. Universal or pan coronavirus vaccines offer a solution not only to the diversity of current and near future coronaviruses but also for the vaccine procurement and deployment issues affecting LMICs. In this project I address the need for a universal coronavirus vaccine by identifying similar immune responses triggered by several different coronaviruses. This information will be used to design and evaluate universal vaccine candidates in a protein subunit vaccine platform. This work is in line with the Coalition for Epidemic Preparedness Innovations' (CEPI's) mission - New vaccines for a safer world. Also, I have connected with researchers and vaccine developers (Incepta) in Rwanda and Bangladesh, respectively, to address COVID-19 vaccine needs in LMICs. Through regular video conferences and an in-person meeting in the last half of the award, I will share my progress with CEPI and my international collaborators. We will plan the next phase of the project to conduct SARS2 variant assessments and preclinical analysis of Incepta's COVID-19 vaccine candidates. The project brings together CEPI and international partners to work toward the goal of improved vaccines for SARS2 that will have a true global impact especially for people in LMICs. All reagents, models, and data will be shared on CEPI approved platforms.",,-99,University of Saskatchewan,320216.57,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2021 +P26082,473353,"Understanding mechanisms coronavirus cross-reactivity, immune durability, and pan-coronavirus vaccine protection","The COVID-19 (Coronavirus disease 2019) pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the largest public health crisis in modern history. Although COVID-19 vaccines have decreased disease burden, the current vaccines have limited coverage against new coronaviruses or SARS-CoV-2 variants and the COVID-19 vaccines do not offer long-lasting protection. Immune protection generated after coronavirus infection is also short-lived adding further opportunity for new infections and continue disease burden. Next generation coronavirus vaccines strive to achieve broad protection against several viruses at once over a longer period; however, the mechanisms driving broad and long-lived protection against coronaviruses are poorly understood. This project will determine the mechanisms driving broad protection and immune durability in the host against coronaviruses. Specifically, the mechanisms utilized by B cells to induce broadly reactive antibodies and long-lived immune memory will be defined during coronavirus infection. Additionally, our new trivalent protein subunit vaccine candidates formulated with squalene-in-water emulsion (SWE) adjuvant (Vaccine Formulation Institute) designed to broadly protect against SARS-CoV-2 variants and sarbecoviruses will be evaluated for their mechanisms of action and immune longevity. This work will bring understanding to the mechanisms of broad protection against coronaviruses and provide valuable evidence for the use of novel vaccines that may be more effective at combating the current coronavirus pandemic and preventing the next one.",,-99,University of Saskatchewan,76662.06,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Vaccine design and administration | Characterisation of vaccine-induced immunity,2022 +P26083,473337,Preclinical Models for Monkeypox Virus Infection and Therapeutic Development,"Monkeypox virus (MPXV) is an emerging virus and its recently identified Clade IIb has caused the greatest global outbreak of this virus family in history. Spread outside of endemic areas associated with atypical transmission modes and clinical presentation initiated the WHO declaration of a Public Health Emergency of International Concern. This large DNA virus causes significant disease with painful lesions and sometimes death often in vulnerable populations such as the young and immunocompromised. Importantly, the effectiveness of orthopoxvirus vaccines vaccination against the new Clade IIb viruses as well as the effectiveness of the vaccine dose sparing strategies that are currently being used are not known. Here we will investigate experimental Clade IIb vs Clade IIa MPXV infection in laboratory models with the goal of developing of a MPXV preclinical model for use in Canadian vaccine development. This model will then be used to understand the mechanisms of MPXV Clade IIb virus disease. For this work, we have three Aims: 1.) to develop preclinical models of MPXV infection using CAST/EiJ mice and black-tailed prairie dogs; 2.) to determine effective modes of transmission for Cade IIb MPXV viruses; 3.) to evaluate approved and newly developed MPXV vaccines against Clade IIb MPXV. Biological sex will also be investigated due to the sex-distribution of MPXV cases in the current outbreak. For this project, we have brought together experts in emerging virus preclinical model development, orthopoxviruses, and virus sequence analysis. Additionally, VIDO has the institutional infrastructure to work with high containment viruses and non-traditional animal models to ensure our success. Together, this project will provide an essential research tool for Canadian scientists and vaccine developers. As well, the results will be important for guiding public health policies to control the outbreak.",,-99,University of Saskatchewan,76662.06,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Research for enhanced understanding of the disease | Development of equitable, accessible, safe and effective vaccines",Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Disease models",2022 +P26084,478959,Regulation of coronavirus cross-reactivity and immune durability for pan-coronavirus vaccine development,"The COVID-19 (Coronavirus disease 2019) pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the largest public health crisis in modern history. Although COVID-19 vaccines have decreased disease burden, the current vaccines have limited coverage against new coronaviruses or SARS-CoV-2 variants. Immune protection generated after coronavirus infection or vaccination is also short-lived adding further opportunity for new infections and continue disease burden. Next generation pan-coronavirus vaccines strive to achieve broad protection against several viruses at once over a longer period; however, the mechanisms driving broad and long-lived protection against coronaviruses are poorly understood. This project will determine the mechanisms driving broad protection and immune durability in the host against coronaviruses. Specifically, the mechanisms utilized by B cells in the Germinal Center (GC) to induce broadly reactive antibodies and long-lived immune memory will be defined during coronavirus infection. To complement the immunological studies, the parts of the virus that stimulate a more cross-protective response will also be identified. This information will then be applied to the evaluation of my novel pan-sarbecovirus vaccine candidates. These candidates were developed on a trivalent protein subunit platform and are formulated with squalene-in-water emulsion (SWE) adjuvant. This work will bring understanding to the mechanisms of broad protection against coronaviruses and provide valuable evidence for the use of novel vaccines that may be more effective at combating the current coronavirus pandemic and preventing the next one.",,-99,University of Saskatchewan,666618.88,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2023 +P26085,481127,Investigation of Mpox virus spillover and spillback at the human-animal interface in the Democratic Republic of Congo,"The re-emerging Mpox virus (formerly monkeypox virus or MPXV) is a global health problem evidenced by the current outbreak involving > 110 countries. Previous outbreaks in people have been driven by virus spillover from an unknown animal reservoir in endemic regions. Although Mpox virus infection in humans can lead to a painful disease that may result in death, the roles of animal reservoirs and the potential of establishing new animal reservoirs globally have been largely neglected. We previously established the International Monkeypox Response Consortium (IMReC) including researchers in endemic regions of continental Africa such as the Democratic Republic of Congo (DRC) as well as international virologists to rapidly mobilize existing Mpox virus expertise to contain the current global outbreak in humans. To address the Mpox One Health knowledge gaps in the DRC as well as the potential risk to wildlife outside of endemic regions, we designed a new project to understand the mechanisms driving transmission at the human-animal interface. To this end, we added a viral disease ecologist to our IMReC team. Leveraging the existing infrastructure from IMReC in the DRC, we will follow positive human cases to determine possible Mpox virus spillover from wildlife animal reservoirs as well as spillback into companion animals driven by infected humans. Sequencing positive human and animal samples will be used to develop a model of transmission chains. Follow-up in vitro studies utilizing primary cell lines derived from Canadian wildlife will determine the potential of Mpox virus to establish endemicity in Canada. Together, our project will provide critical information regarding Mpox virus at the human-animal interface. Through our connections with regional partners and international stakeholders, including the WHO, this information will help design containment strategies in endemic regions and recommendations to prevent endemicity in non-endemic regions such as Canada.",,-99,University of Saskatchewan,375198.56,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Animal and environmental research and research on diseases vectors,Investigation of zoonotic transmission & reservoirs,Canada,,Animal and environmental research and research on diseases vectors | Infection prevention and control,Animal source and routes of transmission | IPC at the human-animal interface,2023 +P26086,443346,COVID-19 Variant Network - Identification of biomarkers that predict severity of COVID-19 patients,"The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are over whelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.",,-99,Dalhousie University (Nova Scotia),78392.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +P26087,481128,"Strengthening global and regional health security through surveillance of emerging Poxviruses in humans, domestic and peri-domestic animals, and wildlife","Historically global poxvirus epidemics have been associated with Smallpox a surge that killed up to 1/3 of infected children during the past centuries. Recently however the emergence of Mpox virial outbreaks and epidemics has heightened awareness that the Poxvirus family is extensive with multiple outbreaks and epidemics currently ongoing. The focus on this research proposal is to undertake a ""One Health"" approach to understanding the relationship between Poxvirus ecology, infection of wild animals, peri-demostic animals, and domestic agricultural animals, and humans. Integrated in our approach is the necessity to understand sociological as well as scientific factors that play a role in the encroachment of human populations on wildlife leading to increased exposure and increased chances of infection with emerging Pox viruses yet not circulating in the human population. We have created an international team of clinicians, scientists, wild-life experts, entomologists, veterinarians, farmers, sociologists, students, government policy makers, and government officials in Africa, and Canada to undertake this multidisciplinary approach to understanding Pox viruses. Dr. Kelvin the NPI of this project is an expert in global emerging infectious disease has established a highly qualified team of investigators who work closely with the Ministry of Agricultural and the Ministry of Health in Rwanda to conduct ongoing surveillance of emerging infectious diseases in Rwanda and Central Africa. With investigators from Rwanda, Democratic Republic of the Congo, Uganda, and Burundi, and two AIMS PhD students and 5 vets. The outcome of the two-year grant from CIHR will provide a comprehensive overview (map) of the state on Mpox and Orthopox viruses (ecology) in central Arica as well as Nova Scotia aiding policy makers in allocating resources for reducing the spread of and impact of poxviruses.",,-99,Dalhousie University (Nova Scotia),375198.56,Animals | Human Populations | Disease Vectors | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience",Investigation of zoonotic transmission & reservoirs | Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts | Evaluation of elimination strategy implementation in different contexts.,Canada,,"Animal and environmental research and research on diseases vectors | Policies for public health, disease control & community resilience",Animal source and routes of transmission | Approaches to public health interventions | Policy research and interventions,2023 +P26088,448874,Health equity and the post COVID-19 condition,"After catching COVID-19, some people do not fully recover, but continue to experience symptoms for weeks or months. So far there is not much reliable evidence, but this post-COVID-19 condition, also called ""long COVID"" or ""long-haul COVID,"" may affect up to ten percent of COVID patients. As with COVID-19 itself, some people seem to be more affected than others, but it is not yet clear what social factors (such as sex, age, ethnicity, and income) might be involved. Another area where evidence is lacking is how other health conditions, such as diabetes, asthma or depression, may interact with COVID-19 to worsen or even prevent long COVID. Ontario collects data on health care use that can be analysed to produce evidence about long COVID. However, doing these kinds of analyses, where there are a lot of variables involved, is complicated and requires some special methods. Artificial intelligence is well suited to this kind of research, because it is very good at classifying and categorizing data with a lot of different features. Our research project will use artificial intelligence to look at the health care use of people in Ontario who have been diagnosed with COVID-19, to see what kind of relationship there is between social factors, existing health conditions, and long COVID. We will engage with community groups and patient groups to help us interpret our findings, and post them in visual form on a publicly available website. Our findings will give policymakers and healthcare decision-makers evidence they need to come up with interventions that are better at preventing and managing COVID-19.",,-99,Bruyère Research Institute,176150.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26104,486363,Pandemic A/H1N1 Influenza Vaccination or Infection During Pregnancy and Offspring Autoimmune Outcomes.,"Pandemic H1N1 Influenza Vaccination or Infection During Pregnancy and Offspring Autoimmune Outcomes. While the safety of influenza vaccination in pregnancy is well established for both mothers and babies around the time of birth, only a limited number of studies have evaluated children's health beyond six months of age. Similarly, although there is evidence that viral infection is associated with some autoimmune diseases in children and adults, the impact of influenza infection during pregnancy on later health of the children is under-studied. We will conduct a study which includes all babies born in Ontario between April 1, 2009 through October 31, 2011 using the province's birth registry. This registry contains records of all babies born in the province and identifies which mothers received the 2009 pandemic influenza vaccine (H1N1) during pregnancy. We will link these birth records with other healthcare databases to find out which mothers had influenza during pregnancy during the 2009 H1N1 pandemic time period. We will also use the healthcare databases to find out which children developed autoimmune diseases in the future, up to 10 years of age, looking at the potential impact of maternal infection and vaccination on these outcomes.!~~!Examining the long-term implications of influenza infection or influenza vaccination during pregnancy will help support pregnant women's decisions on vaccination during pregnancy.",,-99,University of Ottawa,13021.09,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Post acute and long term health consequences | Characterisation of vaccine-induced immunity,2022 +P26107,433692,Identification of the molecular determinants underlying asymptomatic Ebola virus testicular infections and long-term effects on reproductive health,"Ebola virus disease (EVD) outbreaks continue to increase in frequency. Recently, we have witnessed the largest EVD outbreak in recorded history in West Africa, and the ongoing outbreak in the Democratic Republic of Congo is now the second largest. Asymptomatic persistent Ebola virus (EBOV) infections in survivors could result in the initiation of new chains of transmission. This raises important public health concerns. Virus has been found in semen from EVD survivors >500 days following recovery and in the absence of clinical symptoms. Further, sexual transmission of EBOV from survivors resulted in new disease transmission events in multiple EVD outbreaks and represents a major public health and containment concern. Clinical trials with antivirals have suggested that drug treatment has no effect on reducing EBOV persistence within the male reproductive tract. Thus, it is imperative to identify how and when EBOV is transmitted to the male reproductive tract in order to identify treatment and care strategies for patients, as well as help guide containment efforts. The aim of this proposal is to characterize EBOV transmission to the testes and spread of the virus through sexual intercourse. Here, we will identify the mechanisms that help the virus enter into the reproductive tract and the interactions between host cells and the virus that allows for persistence in the testes. We will also examine how these factors relate to sexual transmission using a small animal model of infection. Further, we will also assess the long-term reproductive health complications that are encountered by both male and female EVD survivors in West Africa through questionnaires and analysis of historical samples. This investigation will address critical knowledge gaps in our understanding of this public health concern and will have important impacts for future outbreaks, including informing patient care strategies, outbreak containment and the long-term health of disease survivors.",,-99,University of Manitoba,542968.79,Animals | Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Post acute and long term health consequences",2020 +P26108,471094,"A prospective and retrospective multi-center, cohort study for clinical, virologic and immunologic characterization of monkeypox virus clade IIb by the International Monkeypox Response Consortium (IMREC)","The International Monkeypox Response Consortium (IMREC) is a pan-continental network comprised of subject matter experts with extensive infectious disease experience, including monkeypox virus. With strong track record of equitable collaborative infrastructure during emergencies, we will utilize our diverse team to rapidly investigate critical knowledge gaps to provide rapid evidence to guide policy for the current monkeypox public health emergency of international concern. Members of IMREC include subject matter experts, researchers, clinicians, and community advocates from North America, Africa, and Europe. Coordinated IMREC actions and results-oriented objectives will aim to: I) building network providing rapid real-world evidence to health leaders and policy makers; ii) assessing real-world vaccine effectiveness and serosurveillance across IMREC study sites; and iii) contributing to global monkeypox surveillance and modeling of transmission dynamics across different clades and new settings. For coordination of data acquisition and dissemination, IMREC activities will be divided across the following workstreams: Surveillance, clinical and basic sciences, evidence policy, communication, and engagement implementation. The overall IMREC added value relies on multi-country/sites and cross-sectional study on risk groups in providing robust and effective evidence actions, and scale access to, and uptake of, targeted vaccine effectiveness /impact on at-risk and marginalized groups through understanding of monkeypox.",,-99,University of Manitoba,1945683.1,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Ongoing assessment & evaluation of surveillance,Canada,,"Epidemiological studies | Vaccines research, development and implementation",Disease surveillance & mapping,2022 +P26109,473351,Characterization of monkeypox virus circulation and transmission from wildlife to humans in Africa and identification of wildlife species at elevated risk for infection in Canada,"Recent outbreaks of emerging viruses, including monkeypox virus, have had severe public health and economic impacts across the globe. Monkyepox virus is a neglected emerging virus that can cause severe illness in humans and is endemic in numerous countries across Central and West Africa. Further, the frequency of monkeypox virus outbreaks has been increasing for many years and the ongoing global outbreak of this virus, as well as the 2003 outbreak in the midwestern United States, demonstrates the importance of understanding how increase preparedness and response activities in endemic and non-endemic regions across the world. However, there are critical knowledge gaps regarding the potential impacts of these viruses on wildlife and agricultural species. While prior observations have suggested that rodents are a likely reservoir for MPXV in endemic regions, there is little data implicating specific species. Further, there is a paucity of knowledge regarding the potential impacts of MPXV transmission on wildlife and agricultural species in non-endemic regions or for reservoir establishment. Here, we propose to investigate monkeypox virus circulation within wildlife in endemic regions as well as surrounding areas in Africa. Further, we will also assess the potential impact of monkeypox virus on Canadian wildlife species. Findings from this work will have important impacts on disease surveillance and containment strategies in endemic regions. Importantly, they will inform national monkeypox virus surveillance strategies and reduce the public health, wildlife, agricultural and economic risks for Canadians associated with emerging zoonotic viruses.",,-99,University of Manitoba,574965.45,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Animal and environmental research and research on diseases vectors,Investigation of zoonotic transmission & reservoirs,Canada,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2022 +P26111,459285,Correlates of COVID-19 vaccine-induced protection and host factors that affect immune response,"Background: Canada is seeing a COVID-19 resurgence as SARS-CoV-2 variants continue to emerge globally and herd immunity remains elusive. It is unclear whether there will be a decline in immune protection over time, or with the emergence of viral variants. Methods: From December 2020 to June 2021, invitations went out to select Ontario Health Study participants requesting that they complete an online questionnaire and submit dried blood spot samples. The questionnaire includes details around vaccination, previous COVID-19 infection, and underlying medical conditions and medications taken. The study included 10,569 participants (age 21 to 93), with 62% women. Collection of second dried blood spot samples is underway. Dried blood spot samples will be tested for antibodies to SARS-CoV-2 (anti-spike IgG, anti-receptor binding domain of spike (RBD) IgG, and anti-nucleocapsid (N) IgG) and will undergo DNA extraction and genotyping. Data will be linked to COVID-19 lab results and hospitalization data, including ICU admission and death. Objectives: Measured levels of vaccine-induced immune markers (antibody levels) will be related to vaccine effectiveness by comparing incidence of SARS-CoV-2 infection, hospitalization, and mortality in a population of vaccinated and unvaccinated participants. We will also assess variation in immune response to vaccination by viral variant, vaccine factors (such as type, product, number of doses, interval between doses, time since vaccination) and intrinsic host factors (such as age, sex, genetics, and comorbidities). Implications: Identifying immune correlates of protection will be important because they can be used as surrogate endpoints in assessing vaccine efficacy, and the durability of protection over time will provide insights into the necessity for booster vaccination. Also, identification of host and vaccine factors that affect immunity will allow for tailored recommendations regarding vaccine distribution.",,-99,"Ontario Institute for Cancer Research (Toronto, Ontario)",393525.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Vaccines research, development and implementation",Prognostic factors for disease severity | Characterisation of vaccine-induced immunity,2021 +P26112,459190,mamawohkamatowin: working together to understand the house and COVID-19 in a Saskatchewan First Nation Community,"Aim: This project aims to increase health and well-being by considering how the house impacts COVID-19 on Sturgeon Lake First Nation (SLFN). Research Questions: ((1) In what ways does the house impact COVID-19? (2) In what ways does the house impact the management of COVID-19? (3) Explore SLFN's response to COVID-19 isolation and vaccines. Methods: This research builds on a decade long health research relationship between SLFN and researchers. This team recently completed a co-created research process in which the findings revealed significant relationships between the house and respiratory health on SLFN. House factors were important to health outcomes. Having visible mold and a smell of mold in the house was correlated with both treatment and hospitalization for most respiratory health outcomes. Given that the house is important to respiratory health outcomes understanding the role of the house in COVID-19 in SLFN is an important question of the community. Sturgeon Lake Health Centre has collated data on all CoVID-19 cases in their community including close contact tracing and transmission, and residence for each case. This project will assess if the same houses that are impacted by house factors in our respiratory health survey are more impacted by CoVID-19? These findings will be built on with qualitative methods to further understand how the house impacts isolation and vaccine. The findings will be returned to the community, in ways that are meaningful to the community. Discussions of the findings and strategies for ways and means forward will be co-created with the community, While the results will be beneficial to SLFN policy and processes, the knowledge gained will likely resonate with other First Nation communities so that they are able to co-create similar programs based on their strengths and response to COVID-19. Outcome: Understand and build a strong effective community response to COVID-19.",,-99,University of Saskatchewan,214823.17,Environment,Other,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Community engagement,2021 +P26116,450518,A window on changes in early childhood development with COVID-19 pandemic exposure before and after birth: the Ontario Birth Study,"Stress early in life, even before birth, can have a long-term impact on the development of children. The COVID-19 pandemic has been a major source of stress for families both from the disease itself as well as from measures taken to control it, such as lockdowns and school closures. As yet, we know little about the short and long-term impacts on young children and on children who were exposed during prenatal development. This information will be critical for clinicians who care for the children and their families and also for educators of young children. The Ontario Birth Study, with its child follow-up, provides a unique opportunity to assess changes in child development before, during, and, eventually, after the pandemic. We have recruited mothers in early pregnancy and followed them through the pregnancy and early postnatal period since 2013. Over 3000 mothers have participated so far and about 300 were pregnant during the pandemic period. Since 2018, we have followed up with the mothers and their children at 8, 24, 36, and 54 months with assessment of child development at 24 and 54 months. Over 1600 children have some follow-up and over 300 at 24 months and over 200 at 54 months have been assessed during the pandemic. We propose to compare general childhood development at 24 months and socioemotional development at 54 months in children before and during the pandemic. We will also compare how children are functioning during periods of lockdown and school closure compared to other times during the pandemic and before the pandemic. In addition, we will do an initial assessment of brain development in children at 8 and 24 months in children who were exposed to the pandemic before and/or just after birth using a new assessment approach. The information we gain will be shared with clinicians who work with children and with early childhood educators. This will help them better adapt their approaches, if needed, to account for the pandemic impact.",,-99,Sinai Health System (Toronto),121524.65,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Pregnant women | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26117,430565,Assessing the impact of the COVID-19 pandemic on social and health outcomes among young people: A mixed-method comparative analysis in Canada and France,"Youth (<30 years) are among the most at risk for longer-term social and health consequences due to COVID-19-related public health measures (e.g., physical distancing) and the associated social and economic impacts, including unemployment, as well as isolation from their social networks and disruption to their education during key periods of the early life course. To advance evidence and to inform adaptive social, economic and public health responses among youth, we are prepared to rapidly launch a one-year multi-site mixed-methods study. Our aim is to generate new context-sensitive and population-specific data to document how policy and program responses can be optimized to improve the lives of youth in two key international settings: Canada and France. While both Canada and France share some commonalities (e.g., high-income countries, publicly funded health care systems), there are many important contextual differences (e.g., severity and evolution of national and regional COVID-19 curves, economic support/employment insurance programs, community-based responses) that will benefit from empirical investigation as they relate to youth population health. We will conduct a multi-site concurrent mixed-methods study that includes: (i) a series of longitudinal qualitative research activities including semi-structured interviews with youth from across different jurisdictions in Canada (n=30) and France (n=30); (ii) interviews with key stakeholders (n=10 in each setting); and (iii) two national online cross-sectional surveys in both Canada and France with youth (at 6-month intervals). Throughout the duration of the proposed study we will engage in integrated knowledge translation and exchange (KTE) activities to systematically engage in rapid-cycle evaluation and advance actionable findings, including findings that are of relevance to national, federal and local policies and programs that can have an impact on youth social and health outcomes.",,-99,University of British Columbia,133072.34,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +P26118,473349,"A FOCUS on youth mental health and substance use-related outcomes, inequities and trajectories during COVID-19 and beyond: A mixed-methods study in Canada and France","The COVID-19 pandemic has presented the potential for lasting consequences for inequalities and vulnerabilities to manifest across subsequent stages of the life course - a trend that will have significant impacts on today's generation of adolescents and young adults ages 15-29 years. Globally, including within Canada and France, youth have experienced among the most severe social and economic consequences resulting from the COVID-19 pandemic, with emerging evidence indicating that youth mental health and substance use (MHSU) inequities have deepened. The proposed three-year study will extend our team's existing mixed-methods Canada-France research infrastructure to focus on youth MHSU-related outcomes, inequities, and trajectories as Canada and France continue efforts to move into renewal and recovery. While each country shares some central commonalities (e.g., national health care systems), there are also important contextual differences (e.g., socio-political and -cultural differences; regulatory policies for substances, including cannabis and alcohol) that will benefit from comparative investigations across time. Specifically, we will conduct an annual national online repeat cross-sectional survey in both Canada and France with youth (n=7,000) that also features a nested virtual cohort (n=1,500). We will also conduct annual qualitative semi-structured interviews with youth from across different jurisdictions in Canada (n=30) and France (n=30). Throughout the duration of the proposed study we will engage in integrated knowledge translation and exchange (KTE) activities to systematically engage in rapid-cycle evaluation and advance actionable findings, including findings that are of relevance to national, federal and local policies and programs that can have an impact on youth MHSU-related outcomes.",,-99,Université de Montréal,76662.06,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26121,465742,Using a Restorative Approach to Create Communities of Care in the Long-Term Care Setting,"It has become increasingly common that aging members of our population require healthcare services to support them. Many Canadians spend their final years in long-term care (LTC) facilities as a result. LTC facilities have been under scrutiny in recent years with respect to quality of care and inadequacy of resources, along with concerns about their increased privatization. The COVID-19 pandemic exposed the vulnerabilities of the state of LTC facilities across Canada. There is broad acknowledgement that improvements must be implemented to make the experience and safety of residents of LTC facilities better. Our intended research is interested in understanding the experiences of harm that residents, family members, and healthcare workers have encountered, particularly those during the COVID-19 pandemic. This proposed project will aim to listen to the stories of patients, families and healthcare workers who have been adversely affected by restricted visitation policies, the loss of residents, and burnout, as a way to better understand the context of LTC, to facilitate a Restorative Community of Care for healing, and to learn from these situations to inform subsequent action. This initiative will be facilitated using a restorative approach and will be comprised of three phases: listening to understand, planning for future actions, and reporting and evaluating the results of this process. A restorative approach is a principle-based approach that fosters a relational way of thinking and being and is carried out through facilitated dialogue with the intention of speaking openly about the harm experienced and to work together to heal from that harm and to learn from the past to improve the future. This approach supports respect, dignity and mutual care and concern between people, communities, healthcare providers, and the health system.",,-99,"Interior Health Authority (Kelowna, BC)",27291.49,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery,2022 +P26122,480720,Sex Differences in CT Airway Measurements and their Relationship to Post-Acute COVID-19 Syndrome,"Funding the travel to this multidisciplinary, international conference aligns with the priorities in the mandate of ICRH. Attending conferences and presenting research to leaders and peers in one's research field is a key training and development opportunity for graduate students like myself, which is supportive of Priority A: Preparing Future Capacity. Thus, supporting my conference attendance aligns with the goals of ICRH to support the robust and inclusive development of future leaders in the field. In addition, my research focuses on deepening our understanding of post-acute COVID-19 syndrome, arguably one of the most important current challenges in respiratory health in Canada. A task of this magnitude is dependent on collaboration across multiple disciplines, ranging from clinical medicine to imaging research, in alignment of Priority B: Accelerating Knowledge Through Collaboration. By presenting my research at ATS, I will be able to increase its exposure within the field and facilitate face-to-face discussions with potential collaborators with similar research goals. At the meeting, there will be the potential to form connections that will result in future collaborative research projects and subsequent publications.",,-99,University of Western Ontario,1107.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2023 +P26123,460298,Attitudes and Aspirations: The indirect effects of educational disruption on the mental health and wellbeing of children and adolescents during the COVID-19 pandemic.,"The majority of children have reported worsening of their mental health (MH) since the onset of the COVID-19 pandemic. One important way in which the pandemic has impacted children is through disruptions to school. This project examines the impact of COVID-19 related education disruption on children's MH and wellbeing. School helps children and youth develop interests, autonomy, and attitudes towards learning that inform their self-concept and their future aspirations. Although the term learning loss has been used to describe lost academic growth, children have also experienced losses to the non-academic factors that may be critical to their MH. Our research over the last 18 months shows that simply opening classrooms, while maintaining COVID-19 public health-related measures at school, was not sufficient to improve children's MH. This suggests that children rely on other factors besides academic instruction at school for their wellbeing. We will test the associations between non-academic factors (e.g., motivation and engagement, autonomy, connectedness) during the pandemic and children's MH outcomes among a large sample of children. With few studies exploring the aspects of school that have been impacted by the pandemic, our team of child and youth MH experts will identify the indirect losses that children have experienced that are critical to the success and wellbeing of children. In addition, we will examine whether some children are disproportionately impacted by these non-academic school factors (e.g., based on socioeconomic status, gender identity, race/ethnicity, and diagnosis of pre-existing mental health and/or neurodevelopmental disorder) resulting in greater MH risk. By determining the indirect losses that children have experienced due to education disruption, and the effect of these on children's MH, this study will inform clinical and educational programs to improve children's MH and educational outcomes as we transition to post-pandemic life.",,-99,Hospital for Sick Children (Toronto),394784.57,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26124,459234,Better or Worse? Real-time impact of COVID-19 re-opening among children with and without mental health and neurodevelopmental disorders over time.,"The overall aim of this project is to understand the real-time impact of the COVID-19 public health emergency measures on children's mental health (MH) as our society re-opens, and possibly closes again, over the coming year. In our large sample of children and families with and without pre-COVID mental health and neurodevelopmental problems, we have previously shown that the majority of children experienced a significant negative impact to their MH during the pandemic. However, up to 30% of children reported no MH concerns, or even improvement of their MH during school and recreation closures. From self- and parent-online report of MH symptoms, and using the infrastructure that we have successfully established, we will now determine whether these MH impacts are long-lasting. This study will examine the roles of sociodemographic factors (e.g. household income, race/ethnicity), COVID-19 factors (e.g. vaccination status), child and family-level factors to understand what places a child at increased or decreased risk of MH problems during societal re-opening. Lastly, we want to understand whether children whose MH initially improved, during societal closures, experience increased MH problems as society re-opens. The results of this study are essential for identifying children at risk for poor MH and improving their outcomes. Our experienced team and established partnerships will ensure that study data are used to advocate for children's needs and to inform public health decisions about the societal re-opening process over the coming year and into a post-pandemic period.",,-99,Hospital for Sick Children (Toronto),332998.59,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26125,476017,Toronto Hospitals' Support of Healthcare Worker Mental Health: Learning from Experiences in the COVID-19 Pandemic to Do Better in the Future,"The healthcare work environment has historically caused occupational stress injuries in healthcare workers (HCWs). Stressors associated with the COVID-19 pandemic have further increased this risk. The pandemic also created recognition of the need for effective mental health supports in HCWs. Many organizations implemented HCW mental wellness programs. Initial reports on program structure and/or plans have been published, but a review of what programs have been used, the rationale for these programs, and reports on outcomes and qualitative experience of program implementation are lacking. Now is the time to learn from experiences during the pandemic, in order to benefit from the knowledge created throughout the pandemic. This project will answer the question: How did Toronto Hospitals provide mental health support to their staff during the COVID-19 pandemic, and what was the experience of those who participated? We will start by exploring the mental health programs implemented in Toronto hospitals in response to COVID-19, selecting 2-3 organizations to be the subject of case studies. We will recruit program facilitators, organizers and hospital staff who received support to participate in individual interviews and/or focus groups, to learn about their firsthand experiences facilitating, organizing and participating in programs. We will review and reflect upon the transcribed interviews, looking for topics that consistently arise, as well as similarities and differences in individuals' experiences within each case. We will then compare between cases to identify trends related to success or failures which may indicate what approaches should or should not be taken in the future. Findings will inform the development of a framework or guideline that will be shared with hospital administrators and other individuals involved in implementing mental health support for HCWs to improve future program implementation.",,-99,Sinai Health System (Toronto),77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2022 +P26126,481270,"Assessing mpox virus susceptibility, transmission, host immune responses, and virus evolution in key Canadian livestock species","The current outbreak of monkeypox (mpox) virus has resulted in over 85,000 cases globally, and 1400 in Canada. Public health measures and vaccination have limited the spread of mpox in Canada. Concerns about future outbreaks remain, as cases continue to be reported. At present, multiple rodent and squirrel species have been identified in endemic countries as viral reservoirs. Therefore, each new case of mpox in Canada poses a risk that the virus may spread to animals and become established in Canada. Currently, it remains unknown whether livestock can be infected and what is the threat posed to the Canadian agriculture sector. A similar situation was seen in cattle in Brazil with vaccinia virus (a related virus). This virus became endemic in cattle in Brazil and has caused significant economic costs due to reduced milk production. Moreover, it was shown that agricultural workers in endemic areas may be infected due to spillback and are unable to work due to quarantine requirements, thereby adding costs to the health system. Thus, there is a risk that mpox could be introduced into agricultural animals within the Canadian livestock sector directly threatening trade, food security, and the health of workers. We will determine the risk of mpox infection in livestock and use the information to develop risk mitigation and control strategies. Specific Aims: 1) Characterize mpox infection in livestock to determine disease manifestations. 2) Evaluate mpox viral replication in animal cell lines 3) Investigate environmental contamination in the agricultural setting and develop protocols that can be implemented in the event of an outbreak Our group has experience in clinical, veterinary, and basic science, specifically in emerging viruses. We are well positioned to carry out this work and our study will be important to determine the risk of mpox infection in livestock. We will coordinate our results with key stakeholders for a rapid response.",,-99,Vaccine and Infectious Disease Organization (Sask.),373697.77,Animals | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Research for enhanced understanding of the disease | Investigation of zoonotic transmission & reservoirs,Canada,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Infection prevention and control","Pathogen morphology, shedding & natural history | Animal source and routes of transmission | IPC at the human-animal interface",2023 +P26127,494271,"Investigating the genomic epidemiology, transmission, and infectivity of the non-influenza respiratory viruses","Respiratory viruses are a significant cause of morbidity and mortality and a burden to the healthcare system. The COVID-19 pandemic has demonstrated the potential of molecular testing and sequencing to advance our understanding of respiratory viruses. While considerable research has been done to date on influenza virus and respiratory syncytial virus, others such as parainfluenza, human metapneumovirus and the seasonal coronaviruses have not been as thoroughly characterized. This is despite the significant impact they have on the health of Canadians. The objective of this proposal is to develop tools for identifying and characterizing non-influenza respiratory viruses in circulation in different patient groups. Additionally, we will collect real-world on transmission and infectivity in hospital settings. Specific aims: 1) Characterize the genomic epidemiology of circulating respiratory viruses in Ontario. 2) Compare genomic differences between hospitalized, long-term care and community cases of respiratory virus infection. 3) Understand transmission dynamics and infectivity in long term care and nosocomial outbreaks. This proposal will address key questions on viral transmission and evolution as well as develop tools that can be immediately shared with the clinical community for ongoing surveillance. Additionally, it will provide valuable data that can improve hospital infection control practices and limit outbreaks. Our group has an established record of translational research in respiratory viruses. Dr. Kozak is a clinical microbiologist and Clinician-Scientist. He has expertise in developing diagnostics assays. This proposal is being done in conjunction with TIBDN as well as collaborators at other microbiology laboratories to facilitate easy collection of patient samples. Collectively, the findings from this project have potential to better prepare Canada for future respiratory virus epidemics.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",73558.84,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Other,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other | Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics",2023 +P26128,460381,COVID time capsule: Learning from the experiences of children with disabilities and their parents throughout the COVID pandemic to improve supports and services in healthcare and education,"What's the issue? Children with disabilities and their families have been uniquely affected by measures that were put in place to limit the spread of COVID-19. Children's therapies and medical services were often reduced, changed to virtual delivery, or cancelled altogether; when schools closed children lost access to many supports; and many children lost opportunities to interact with others and to participate in physical activities. All of this has taken a great toll on the health and well-being of children and families. As we plan services in the post-Covid period, we need to i) address the challenges that children and families have faced during Covid; and ii) use the resources developed during Covid (e.g., technology) to improve the services and supports for children and families, particularly in healthcare and education. In this study we want to learn about children and parents' experiences at the time of COVID-19, to understand: What services did children and families miss out on because of COVID? What issues were made worse by Covid? What supports and services do children and parents need and want, now and into the future? What needs to be done in order to improve supports in healthcare and education for children and families after Covid? Methods: Our research team is made up of 8 researchers, 4 parents and 4 youth, who will all work together throughout the study. 1)30 youth ages 8-21 will complete a visual Covid time capsule and a follow-up interview. Their parent/guardian will also participate in a separate interview. 2)500 youth and parents will complete a survey regarding their need for services and supports after the pandemic. What are we going to do with this information? We will develop different materials for healthcare providers and educators: infographics; tip sheets; podcasts; video; policy briefs; and #DisabilityAfterCovid campaign on social media. We will also have a special research presentation for families and children/youth.",,-99,McMaster University,325424.3,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26129,450649,COVID time capsule: Learning from Covid-related experiences of children with disabilities and their parents to improve health supports and services,"What's the issue? Children with disabilities and their families have been uniquely affected by measures that were put in place to limit the spread of COVID-19. Children's therapies and medical services were often reduced, changed to virtual delivery, or cancelled altogether; when schools closed children lost access to many supports; and many children lost opportunities to interact with others and to participate in physical activities. All of this has taken a great toll on the health and well-being of children and families. As we plan health services in the post-Covid period, we need to i) address the challenges that children and families have faced during Covid; and ii) use the resources developed during Covid (e.g., technology) to improve the lives of children and families. In this study we want to learn about children and parents' experiences at the time of COVID-19, to understand: What services did children and families miss out on because of COVID? What issues were made worse by Covid? What supports and services do children and parents need and want, now and into the future? What needs to be done in order to improve health services for children and families after Covid? Methods: Our research team is made up of 4 researchers, 5 parents and 5 youth, who will all work together throughout the study. 30 youth ages 8-21 and 30 parents/caregivers will be invited to participate in the following activities: 1)Youth will complete: i) a short survey; ii) a visual ""Covid time capsule"" where they will draw or paste images that speak to their experiences in different areas of life; and iii) an interview 2) Parents will complete: i) a questionnaire; ii) an interview What are we going to do with this information? We will develop and make available different materials for parents, youth, and service providers: infographics; tip sheets; podcasts; cartoon; video; and #DisabilityAfterCovid campaign on social media.",,-99,McMaster University,121568.44,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26130,451026,A tailored EDUcational intervention to increase COVID-19 vaccine uptake among hesitant Canadian incarcerATEd people (EDUCATE study),"People in prison are a key population for improving COVID-19 vaccine uptake. While vaccine uptake rates have been historically low in correctional facilities, the provision of education by trusted individuals may be key to improving uptake. With the overall goal of increasing COVID-19 vaccine uptake and improving COVID-19 vaccine confidence among people incarcerated in federal prison, we will design and evaluate a tailored COVID-19 educational intervention. The intervention will address key barriers to COVID-19 vaccine uptake that were recently identified through individual interviews with vaccine-hesitant people in federal prison. Correctional-facility nurses will then be trained to deliver the educational intervention, and its impact on vaccine uptake and vaccine confidence will be evaluated. If the educational intervention is found to improve COVID-19 vaccine uptake and confidence, it could be disseminated throughout the Canadian correctional system (federal and provincial/territorial prisons), and simultaneously adapted to correctional facility staff, to potentially improve vaccine uptake and confidence among thousands of individuals.",,-99,Research Institute of the McGill University Health Centre,79587.57,Human Populations,Unspecified,Unspecified,Unspecified,Prisoners,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy | Health workforce,2021 +P26138,466950,Impact of the COVID-19 pandemic on cognitive inhibition processes in a population with Alzheimer's disease,"Inhibition allows humans to ignore secondary stimuli or inappropriate actions (Bjorklund and Harnishfeger, 1995). This process is essential for human functioning, since it allows us to control cognitive and behavioral performance (Rouch et al., 2019). Conversely, inhibition disorders can lead to an excess of information in working memory or to disinhibition of behaviors. In fact, inhibition is one of the cognitive functions most affected in the different stages of Alzheimer's disease (AD; Amieva et al., 2004). In 2021, during COVID-19, between 30 and 35 million people suffered from AD (WHO). This context had repercussions on the cognitive functions of these people. However, no study has looked at the impact that the context of the pandemic had on the inhibition capacities of people suffering from AD in Quebec. The research hypothesis is that performance in inhibition tests in the AD population will be lower since the COVID-19 pandemic. Health measures have created a context of isolation, where practicing cognitive activities to maintain inhibition performance was difficult. In addition, increased stress is a factor that influences inhibition. In order to determine whether the context of the pandemic has repercussions on inhibition in the AD population, a comparison between the results of the meta-analysis by Kaiser et al. (2018) and the results of a standard neuropsychological battery and a series of tests assessing inhibition will be carried out. Subsequently, participants (with the help of a relative) will answer a qualitative semi-structured questionnaire.",,-99,Université de Montréal,13724.56,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26144,477594,Youth Promotion of Resilience Involving Mental E-health (Y-PRIME),"Vietnamese youth experience many risk factors for poor mental health and well-being, which may lead to poor outcomes over the lifespan. Despite this, resources and supports to promote mental well-being and mitigate risk factors for poor mental health among youth are severely limited in the country. Risk factors identified among Vietnamese youth include pressure for academic success and high academic work load, social and emotional isolation, conflict with parents and teachers, gender roles and struggles with sexual identity. The socioeconomic impact of COVID-19 will likely exacerbate these challenges. Life skills, social and emotional learning and self-management techniques can support youth to navigate challenges that, if unaddressed, may lead to more serious mental health problems. Our proposal is to adapt an evidence-based intervention that promotes life-skills, social and emotional learning and self-management at a population level and is delivered via a mobile app. The intervention will be adapted for use in the Vietnamese context and for delivery via an app in collaboration with a Youth Advisory Council. We will then test it among secondary school students in three Vietnamese provinces and will assess outcomes related to implementation, mental health and well-being, risk factor mitigation and equitable access with a view to scaling-up up the model across the country.",,-99,University of British Columbia,573007.49,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26147,459163,Coronavirus Variants Rapid Response Network: CoVaRR-Net - Extension,"Canadians are concerned about how mutations in SARS-CoV-2, the virus that causes COVID-19, will impact how the virus is transmitted, whether it makes people more sick, and whether immunity conferred through previous exposures to SARS-CoV-2 or vaccination will still be able to fight off a mutated virus. Mutations to SARS-CoV-2 that have these outcomes are called ""Variants of Concern"" (VOC). CoVaRR-Net, a rapid-response Network, will assist in the Government of Canada's overall strategy to address the threat of emerging VOC. The Network will enable the mobilization of Canadian research assets to answer critical and immediate questions regarding threats, such as increased transmissibility, pathogenicity and vaccine resistance, posed by an emerging VOC. CoVaRR-Net will act as Canada's integrated platform for determining how VOCs impact Canadians from diverse communities and demographics. We will work collaboratively with national and international bodies such as the National Microbiology Lab, provincial/territorial public health labs, and the Canadian COVID-19 Genomics Network that are tracking how SARS-CoV-2 is mutating in real time. Central to CoVaRR-Net's service work will be a newly created Biobank for rapid sharing of samples and data with other biobanks across Canada in order to have a harmonized approach to the war on COVID-19. Built on a foundation of eight thematic areas (Immunology & Vaccine Protection, in vitro & in vivo Characterizations, Functional Genomics & Structure Function of VOCs, Viral Genomics & Sequencing, and In Silico Modelling & Computational Biology, Public Health, Health Systems & Social Policy Impacts, Indigenous Outreach and Knowledge Mobilization), CoVaRR-Net is poised to contribute to the Canadian effort to mitigate the impact of harmful VOCs on citizens of Canada and on the world population.",,-99,University of Ottawa,7253572.92,Viruses | Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2021 +P26148,443333,COVID-19 Variant Network - Analysis of Antibody Neutralization Efficiency and Cellular Immunity in SARS-CoV-2-Positive Individuals Identified in At-Risk Individuals,"As the COVID-19 pandemic continues its deadly course around the globe, research efforts are closely focused on viral immunity, antibody responses, and vaccine development. Increasing data from multiple reputable international medical sources now indicate that exposure to the COVID-19 virus induces an antibody response in nearly all exposed individuals. However, questions remain about the protective value of these antibodies against repeat exposure to the virus and how long this protection will last. Furthermore, it is unclear whether there are differences in the virus-neutralizing ability of antibodies produced by asymptomatic carriers of the virus and individuals that develop severe COVID-19 infection. Answers to these important questions will enable us to predict the likelihood of additional waves of COVID-19 as well as inform public health efforts and vaccine development. For our study we will recruit a total of 1,000 healthy primary school teachers, daycare personnel, frontline medical workers in hospitals, and elderly people living in retirement homes. We will monitor them every two weeks for the virus and monthly for antibodies. We will regularly report back the data to the participants. The information learned from our laboratory will have five major outcomes: 1) It will enable early detection of infection and thereby greatly reduced the spread of the virus; 2) We will acquire a better sense of the numbers of asymptomatic and symptomatic individuals exposed to COVID-19; 3) Antibodies in the blood of those infected will be tested to see how well it can neutralize the virus; 4) Critical information about immunity to COVID-19 and how long the immunity will last will be shared with the scientific community and local/regional/national health authorities; and 5) This new knowledge will help vaccine developers make the right decisions about how to create their vaccines and how to give them to all of us.",,-99,University of Ottawa,78392.55,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2021 +P26149,429223,Analysis of Antibody Neutralization Efficiency and Cellular Immunity in SARS-CoV-2-Positive Individuals Identified in At-Risk Individuals,"As the COVID-19 pandemic continues its deadly course around the globe, research efforts are closely focused on viral immunity, antibody responses, and vaccine development. Increasing data from multiple reputable international medical sources now indicate that exposure to the COVID-19 virus induces an antibody response in nearly all exposed individuals. However, questions remain about the protective value of these antibodies against repeat exposure to the virus and how long this protection will last. Furthermore, it is unclear whether there are differences in the virus-neutralizing ability of antibodies produced by asymptomatic carriers of the virus and individuals that develop severe COVID-19 infection. Answers to these important questions will enable us to predict the likelihood of additional waves of COVID-19 as well as inform public health efforts and vaccine development. For our study we will recruit a total of 1,000 healthy primary school teachers, daycare personnel, frontline medical workers in hospitals, and elderly people living in retirement homes. We will monitor them every two weeks for the virus and monthly for antibodies. We will regularly report back the data to the participants. The information learned from our laboratory will have five major outcomes: 1) It will enable early detection of infection and thereby greatly reduced the spread of the virus; 2) We will acquire a better sense of the numbers of asymptomatic and symptomatic individuals exposed to COVID-19; 3) Antibodies in the blood of those infected will be tested to see how well it can neutralize the virus; 4) Critical information about immunity to COVID-19 and how long the immunity will last will be shared with the scientific community and local/regional/national health authorities; and 5) This new knowledge will help vaccine developers make the right decisions about how to create their vaccines and how to give them to all of us.",,-99,University of Ottawa,1502776.14,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +P26150,486303,Investigating the Antagonization of IgA-Mediated Mucosal Immunity by the SARS-CoV-2 Accessory Protein ORF8,"Causing over 6.6 million deaths since its emergence in 2019, SARS-CoV-2 continues to threaten global health despite the development of effective vaccines that have mitigated disease severity. Although current intramuscular immunization regimens mediate decreased symptomatic disease, their capacity to prevent asymptomatic viral spread and infection is limited. As a result, mucosal vaccine development has been initiated in hopes of generating an immune response directly in the lung mucosa to prevent the establishment of infection and restrict SARS-CoV-2 spread. To this end, it is essential to understand the mucosal immune response to SARS-CoV-2 and the escape mechanisms employed by the virus, which are unfortunately not well pursued. I recently discovered that SARS-CoV-2 Open Reading Frame (ORF) 8 protein downregulates the polymeric immunoglobulin receptor (pIgR). This receptor is a key mediator of mucosal immunity as it transcytoses dimeric IgA (dIgA) from the blood to the mucosa of airways in the lungs, which is the primary site of SARS-CoV-2 infection. This discovery led to the hypothesis that ORF8 antagonizes dIgA-mediated mucosal immunity by downregulating pIgR, thus promoting SARS-CoV-2 infection of lung epithelial cells. This project aims to elucidate the molecular mechanism of ORF8-mediated pIgR downregulation by investigating the interaction between both proteins via mutagenesis. Furthermore, we seek to determine the effect of ORF8 from SARS-CoV-2 and its variants in the antagonization of dIgA transport by pIgR. This study will advance our knowledge of SARS-CoV-2 immune evasion mechanisms and highlight ORF8 as a potential mucosal vaccine target due to its capacity to antagonize mucosal immunity.",,-99,McGill University,13021.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P26151,454576,Increasing recruitment and retention of Anglophones to a prospective cohort of people who inject drugs in Montreal,"People who inject drugs (PWID) are a key population at risk of poor health outcomes and frequently experience difficulties in accessing timely healthcare. Much of the data on PWID in Quebec is derived from samples that are largely or entirely Francophone. As a result, it is not possible to explore differences between language communities in access to care. This project is a collaboration with community organisations to increase the recruitment of English-speakers to an existing longitudinal cohort study of PWID, the HEPCO study, and produce data on access to care stratified by language community. The HEPCO study, based in Montreal, has provided critical data on the health of PWID for nearly 20 years. Activities to increase recruitment and retention of Anglophones to HEPCO will be designed and implemented in partnership with community organisations. HEPCO data will be analysed to assess differences between language communities in access to essential health care, such as harm reduction services, drug treatment services, COVID-19 vaccination, and HIV and hepatitis C testing. This study will inform the development of more inclusive health services. It will also have implications for researchers across Canada by providing insights into approaches for increasing linguistic minority participation in health research.",,-99,Centre hospitalier de l'Université de Montréal (CHUM),78943.34,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Vaccines research, development and implementation | Health Systems Research","Community engagement | Vaccine logistics and supply chains and distribution strategies | Medicines, vaccines & other technologies",2021 +P26153,443212,COVID-19 Variant Supplement - Supporting mental health and preventing moral injury among long term care+ workers: A mixed methods tool kit development and implementation study,"Long term care+ (LTC+) is at the center of tragic outcomes of COVID-19 and LTC+ workers are facing pronounced risk for occupational stress related injuries including moral injury. Moral injury results from guilt and/or shame that accompanies knowing what is needed yet being unable to do what is needed owing to constraints outside one's control (Dean, 2020). For LTC+ workers, moral injury may occur from experiences such as guilt over being required to ""police"" end of life visits where family members are only permitted to touch dying loved ones through gloved hands. Moral injury is being newly and necessarily applied to understand occupational stress of health care workers during COVID-19 because compared to individually focused concepts such as burnout, moral injury locates the source of problems in the structures and processes in which individuals are immersed. Our research question is: how do we support mental health and help prevent moral injury among LTC+ workers? Our objectives are to: 1-gather stakeholder evidence about worker mental health needs and moral injury risks; 2-collect stakeholder assessments of a selection of mental health support/moral injury prevention tools; 3-create and disseminate a mental health support/moral injury prevention toolkit tailored to LTC+ workers in pandemic conditions; and 4-develop theory and evidence-based implementation strategies for scaling and spreading our toolkit.",,-99,University of Calgary,39196.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +P26154,475091,Policy obstacles and opportunities in providing community-building resources and supports for the long-term care workforce,"During the COVID-19 pandemic, long-term care (LTC) residents were especially vulnerable to infection and death, and the stress on LTC employees has been huge. A type of stress they experienced is moral distress. This is the pain or anguish of knowing but being unable to do what is needed because of circumstances outside their control. For LTC employees, moral distress happened when they had to force confused residents into their rooms, or were unable to attend to residents calling out for help. Moral distress among employees is important to recognize because, compared to health issues such as burnout which focuses the problem on the individual, moral distress focuses on problems with the contexts and processes in which individuals do their jobs. We need to fix problems with contexts and processes, but in the meantime, we need transformational policies that can increase resources and supports to help LTC employees manage or avoid the distress. We did foundational research to listen to LTC employees about their moral distress experiences and what can help mitigate their distress. We learned that employee moral distress is substantial but can be reduced by having more and better ways to connect and collaborate with their co-workers and managers. Our purpose in this project is to create policy recommendations for increasing LTC employee resources and supports for connecting and collaborating with co-workers and managers. To create these recommendations, we will study provincial LTC policy as well as the policies of a variety of LTC homes. We will obtain input from our stakeholders about how to use our findings to create policy recommendations and we will share our recommendations with policymakers. In the long term, we expect our recommendations can lead to policy that helps LTC employees stay in their jobs and provide good care.",,-99,University of Calgary,109655.17,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P26156,429399,BLT-Lung mice for the rapid evaluation of COVID-19 therapeutics,Controlled animal studies of candidate anti-COVID-19 therapies are required to rapidly identify the most promising drugs and safely advance them to trials in human subjects. The animal models that best predict what therapies will perform similarly in humans are those that closely replicate the human condition. Primates closely resemble humans but rapid high-throughput evaluation of drugs in this animal model is not feasible for economic and ethical reasons. We are producing a unique mouse model that contains human lung implants that support SARS-CoV-2 infection and a human immune system capable of responding to the infection. This animal model thus closely replicates COVID-19 disease seen in humans. These mice are in high demand to evaluate drugs that have already proven safe for the treatment of other diseases and drugs showing strong anti-SARS-CoV-2 effects in the laboratory. We will produce these mice and rapidly assess some of the most promising therapeutic candidates that have been identified as potential treatments of COVID-19. These studies will allow us to rapidly determine the impact of numerous promising compounds in a sophisticated animal model that closely resembles human COVID-19 disease in order to better predict their success in humans and speed their course towards clinical use.,,-99,University of Saskatchewan,190120.21,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2020 +P26158,462711,Qanuinngitsiarutiksait 3: Developing mechanisms to ascertain Inuit data sovereignty in Manitoba,"Inuit have long been underrepresented/invisible in the ""data world"". Despite decades of data being collected, Indigenous peoples continue to experience considerable inequities. This has led Indigenous nations to call for data sovereignty, which can be defined as ""managing information in a way that is consistent with the laws, practices and customs of the nation-state in which it is located"". Our overarching goal is to strengthen MIA's ability to engage and respond to pandemics, by expanding its data sovereignty capacity. This proposal is a first step towards the development of an Inuit-centric, state-of-the-art data sovereignty infrastructure built to support MIA's role as an advocate and service delivery organization serving the needs of Inuit. This project will, 1.Develop Inuit Qaujimajatuqangit-informed governance and management policies to ensure Inuit data sovereignty; 2.Create and implement a respondent driven survey mapping where Manitoba Inuit reside, their circumstances and their needs; 3.Survey Manitoba Inuit to document the impact of COVID-19; and 4.Create a data infrastructure to expand MIA's ability to document, advocate for and improve its COVID-19 and other work, and to support MIA's advocacy with federal, provincial and territorial governments. Our project will result in a sustainable Manitoba-led, MIA-based Inuit infrastructure that can be mobilized quickly to support informed decision-making on emerging issues (pandemics), and document needs for program delivery and advocacy. Our approach aligns with Indigenous self-determination and Inuit' aspiration for data sovereignty. Our work will be grounded in discussions (Integrated Knowledge Translation adapted to reflect Inuit Qaujimajatuqangit) with feedback provided by the Isumataiit Sivuliuqtii (Inuit Elders).",,-99,University of Manitoba,196065.15,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Policy research and interventions,2021 +P26159,468884,"Optimizing pandemic preparedness through ongoing assessment of public attitudes, intentions and behaviours in relation to COVID-19 prevention measures and their impacts: Increasing the capacity of the iCARE Study","Despite the fact that Canadians, and people around the world are 'done' with COVID-19, the World Health Organization, the US Center for Disease Control and Health Canada are all projecting that new variants of concern are highly likely to develop, and some may be more contagious and/or more severe than previous variants. It is therefore highly probable that behavioural prevention policies, including additional vaccine doses, mask wearing, and distancing, may need to be re-introduced. In fact, many governments (including Canada) are already preparing for how to manage the next wave of the pandemic. This application is seeking to expand our capacity to supply the Canadian government and other partners with data and information to support ongoing pandemic response and preparedness. We are seeking additional funding to hire an additional data analyst and post-doctoral student to help us exploit the data we are collecting through our ongoing CIHR-funded iCARE study. iCARE's objective is to monitor population attitudes, intentions and behaviours in relation to engaging in COVID-19 prevention behaviours as measures become increasingly relaxed/lifted, and in relation to the potential re-introduction of preventive measures if/when this may become necessary. We are also assessing what factors are motivating people to re-engage in these behaviours, in general and among vulnerable groups (e.g., racial & ethnic minorities, women, those with mental/ physical health conditions). The existing infrastructure of the iCARE study will be leveraged so that we may continue to provide timely data to local and international governments to inform policy. We will collect data in Canada and a sample of key countries (i.e., Italy, Ireland, France, Australia, and Colombia) chosen based on their relative position to Canada on the pandemic curve, their diverse policy approaches and impacts, and their geographical and population diversity.",,-99,CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur,78018.29,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2022 +P26160,485642,Uncovering Trauma: A Conversation about PTSD and Moral Injury,"Mental health and trauma are widely recognized topics that have been discussed more openly since the COVID-19 pandemic brought them into the spotlight. According to the Canadian Mental Health Association, it's estimated that around nine per cent of Canadian adults will experience PTSD at some point in their lifetime. Lawson Health Research Institute's Café Scientifique aims to engage the public in the science around trauma. Titled 'Uncovering Trauma: A Conversation about PTSD and Moral Injury,' our Café will bring to the forefront new research in the area of mental health trauma through an engaging discussion that leaves attendees with new knowledge, answers and inspiration. From understanding trauma, PTSD and moral injury, to advancing diagnosis, prognosis and treatment, our globally-renowned researchers in this field will share the importance of addressing this crucial area in health care while sharing information about studies that include at-risk populations like Veterans and health-care workers. Joined by patients, the critical nature of this work will be highlighted through human impact stories. Lawson has successfully held Café Scientifique events since 2008, and continued to hold them even after CIHR funding concluded, except when prevented by pandemic restrictions. We have made purposeful efforts to ensure our panel is gender diverse. It features our Institute's two leading experts in trauma, Drs. Ruth Lanius and Don Richardson. Ensuring this event is open, accessible and welcoming to diverse and underrepresented groups will be a key priority in our planning. We have chosen a venue that is fully accessible and located in our city's downtown core, for ease of access on city bus routes and for those who may be living unsheltered. Knowing that research and discussion around trauma may be triggering for some, we will also ensure we share resources for participants should they be struggling.",,-99,London Health Sciences Centre Res. Inc. (Ont.),4265.06,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26162,485995,Support Group to Expand Toolbox for Patients with Postural Orthostatic Tachycardia Syndrome,"Postural Orthostatic Tachycardia Syndrome (POTS) is dysfunction of the autonomic nervous system causing orthostatic intolerance (Raj et al., 2020). There are many other associated symptoms as the autonomic nervous system affects every body system (Raj et al., 2020). Patients' symptoms can be triggered by a wide variety of environmental factors, including scents, stress, temperature, and more (Knoop & Dunwoody, 2022; Raj et al., 2020). Patients with POTS experience significant diagnostic delays, seeing an average of 7 physicians to get an accurate diagnosis (Herrera & Behm, 2021). Misdiagnosis is common amongst patients with POTS (Knopp & Dunwoody, 2022). There are also significant comorbidities amongst these patients, which can lead to misdiagnoses (Vadas & Cheung, 2015; Yahya & Khawaja, 2020). 90% of patients with POTS are women, yet men experience significantly less of a diagnostic delay than women, demonstrating that bias has an impact on the ability for patients to get care (Herrera & Behm, 2021). More patients have being presenting to their doctors with POTS symptoms, especially as it is one manifestation of Long COVID (Davis et al., 2021). My research will be a proposed intervention committed to providing patients with a formal network of support to help them increase their toolbox of coping mechanisms. Due to the delays in getting treatment for POTS patients in Ontario, it is essential to support patient activation within this community. Support groups have been proven to be a good intervention for people living with chronic illnesses like POTS (Herrera & Behm, 2021; Knoop & Dunwoody, 2022). This intervention will have individual and group components, asynchronous and synchronous components, and will allow members to review the resources on an online platform.",,-99,Laurentian University of Sudbury,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P26165,440041,Developing Glycan-Based Antiviral Prophylactics to Prevent Infection by COVID-19 and Other Respiratory Viruses,"The COVID-19 pandemic has now surpassed 37 million confirmed cases. No vaccine or antiviral drug has yet been approved to prevent the spread of SARS-CoV-2, the causative agent of COVID-19. Moreover, the most vulnerable people are also at risk of severe infection from seasonal circulating respiratory viruses, such as influenza viruses. In the absence of effective vaccines against COVID-19 and most strains of common respiratory viruses, new approaches guided by interdisciplinary research are required. Most viruses initiate attachment to the surface of human cells by interacting with complex carbohydrates called glycans. I aim to identify which subtypes of glycans are used by SARS-CoV-2 and other respiratory viruses for entry and infection of human airway cells. Working with expert carbohydrate chemists, we will design and test glycan-mimicking antiviral molecules that block the interaction with glycans to prevent viral infection. With this project, we will accelerate the development of antiviral candidates to address current respiratory virus infections and to prepare for future emerging viruses.",,-99,"Queen's University (Kingston, Ontario)",79694.66,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +P26167,473345,Preclinical proof of concept studies of a new generation of TLR7/8 agonist used in prevention against respiratory viruses and in immunotherapy against lung cancer.,"A nanotechnology, named FB-631, is a new generation of toll like receptor (TLR) 7/8 agonist known to trigger innate immunity in the lungs. The manufacturing process of FB-631 has been already developed and validated. FB-631 previously showed an excellent safety profile in a phase I clinical trial in human. This new nanoparticle is stable at 4°C (<7 years) and at RT (<7days) and can be stockpiled without loss of activity or integrity. Several crucial steps of the development of this technology have already been completed making the search for novel applications very compelling. Other TLR7/8 agonists, like imiquimod (IMQ), are already on the market and used against warts (antiviral activity) and skin cancers. However, IMQ can only be used by the topical route because of its toxicity when administered otherwise. There is a medical need for a TLR7/8 agonist that can be injected or used by instillation/nebulization. FB-631 is safe and effective when used by instillation/nebulization and is well positioned to fulfill this medical need. Objective of the project: We intend to demonstrate the efficacy of FB-631 to prevent infection by respiratory viruses like the SARS-CoV-2. We also intend to demonstrate the potential of FB-631 in prevention of the implantation of lung cancers tumors and its potential in lung cancer immunotherapy. These proof-of-concept studies will generate convincing data that will support further development of this technology into the clinic. The team: The team combines an expert in the manufacturing of FB-631 (Leclerc) and in respiratory viruses, an expert in SARS-CoV-2 animal models (Baz) and an expert in lung cancer immunotherapy (Blanchet). The three researchers harbor the complementary expertise necessary to reveal all the potential of this technology.",,-99,CHU de Québec,76662.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P26168,431402,"Population-estimable frailty using 'big data' to predict Covid-19 infection and illness severity, Institute of Clinical Evaluative Sciences",N/A,,-99,Institute for Clinical Evaluative Sciences-Toronto,131124.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility,2020 +P26171,495187,"Variability in responses of antimicrobial resistance genes to lifting COVID-19-related measures among different population groups : A comparative study of the general public, university campus community, and marginalized groups","COVID-19 pandemic posed a serious threat to the public health, resulting in an unprecedented level of travel restrictions across our societies. As a result, in Alberta, both domestic and international travel decreased significantly during the travel restriction compared to the previous years, then gradually recovered upon lifting the restriction from 2022-March. Such changes in the governmental measure might have had an impact on the public antimicrobial resistance (AMR), as evidenced by other studies reporting association between travel and AMR (Heß et al., 2019 Env Sci Tech; Ricotta et al., 2014 Am J Public Health), but the impact has not comprehensively been studied. For the first time, our team monitored occurrences of AMR genes in different population groups in Calgary, including the general public, university campus community, and marginalized groups, during the transition period (Oct 2021 - Oct 2022), leveraging multi-disciplinary efforts spanning wastewater-based surveillance (WBS), geography, genomics, computer and statistical sciences. We first (1) sequenced genomic DNAs in wastewaters obtained from wastewater treatment plants (WWTPs; covering > 1M serving population), a university residence hall, and a homeless facility in Calgary during the monitoring period, (2) identified AMR genes from the samples using bioinformatics, and (3) correlated those genes with domestic and international passengers. Many genes of clinical concern (for beta-lactamases, MLS, and fluoroquinolones) increased significantly after lifting travel restriction. Consequently, those genes correlated positively with either domestic or international passengers, depending on the population group (p < 0.05). Our approach emphasizes the significance of travel as a key factor influencing public AMR. Additionally, it highlights that AMR transmission or carriage routes differ among population groups, underscoring the importance of customizing resource allocation for equitable health outcomes.",,-99,University of Calgary,1481.35,Bacteria | Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26172,445092,Advancing methods and analyses to support evidence-informed decision-making on the coordinated use of travel-related measures during public health emergencies of international concern: Lessons from the COVID-19 pandemic,"During public health emergencies of international concern (PHEICs), effective global responses require coordinated action across jurisdictions. During the COVID-19 pandemic, countries have used travel measures to an unprecedented degree and in an uncoordinated way. Our Pandemics and Borders Project is analysing a global dataset on travel measures; systematically reviewing evidence of their impacts; and conducting case studies of decision making in Canada, USA and Hong Kong. Our findings suggest limited scientific evidence and principles to guide complex decisions on using travel measures. Poorly coordinated border management contributes to underreporting of cases, increased disease transmission, and unnecessary economic and social impacts. The proposed project will build on these findings to support evidence-informed decision making on whether, when, what and how travel measures should be used. Our aims are to: 1) comparatively review and apply new methods to assess public health risks from travel during COVID-19; 2) evaluate the effectiveness of mitigating public health risks during COVID-19 of specific travel measures under different conditions; and 3) use findings to develop scenarios and pilot training exercises that simulate decision making on managing borders during PHEICs. We will use systematic reviews, various types of modelling, and viral genomic analyses to newly available datasets. We will focus on our three current case studies, with potential extension to other jurisdictions. Our interdisciplinary team, composed of 5 internationally recognized scholars and 6 outstanding trainees, will work collaboratively with knowledge users in senior national and international positions. We will produce open access datasets, methods and analyses to inform decision makers in government and key international organizations. The primary outcome will be strengthened capacity to make evidence-informed choices that enhance coordinated use of travel measures during PHEICs.",,-99,"Simon Fraser University (Burnaby, B.C.)",513548.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions,2021 +P26176,475102,The collateral effects of COVID-19 public health policies: Perspectives of people who use opioids and those closest to them using a patient-oriented research approach,"The proposed policy research project brings together researchers, policy makers, and knowledge users with lived experience to retrospectively analyze the effects of COVID-19 pandemic public health measures from the perspective of people who use opioids (PWUO), service providers, and families to inform future policy options during the current and future public health emergency responses. The purpose of this study is to analyze public health policies and develop public health emergency response policy options to strengthen pandemic preparedness and responses and mitigate other impacts, such as health system inequity and disparity. Using best practices in patient-oriented research and co-design in policy research, the project team will ensure future policy options are relevant to those who are most impacted by them. This project will advance new and existing partnerships to generate and integrate research findings into public health policy recommendations to inform value-based healthcare practices more broadly.",,-99,Waypoint Centre for Mental Health Care (Ontario),109357.64,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Other secondary impacts | Policy research and interventions,2022 +P26177,486007,"Impacts of COVID-19 and its prevention measures on mental health and social relations in Canada, Australia and Colombia: how to optimize policy strategy to improve pandemic response","The COVID-19 pandemic has caused historic morbidity and mortality as well as economic and social disruption across Canada and the rest of the world. The key to slowing the spread of COVID-19 lies in the adherence of the population to public health prevention measures. However, adhesion implies significant changes in behaviour which can be accompanied by significant personal and social costs. In fact, one of the main reasons for the lifting of many restrictions has been the alleged impact on mental health and social relationships. Although, few studies have assessed the association between the presence/absence of prevention policies and impacts on mental health and social relations. The purpose of this study is to determine and compare the impact of public health measures (masking, vaccine passports, isolation, quarantine) on mental health (e.g., degree of anxiety, depression, anger) and social relations (e.g., degree of isolation, frequency of verbal/physical arguments, rates of separation and divorce) in Canada compared to two countries where prevention measures were much stricter (Australia) and much more lenient (Colombia). This research project is part of the iCARE (International COVID-19 Awareness and Responses Evaluation) Study, an international cross-sectional observational cohort study designed to assess public awareness, attitudes and behaviours regarding COVID-19 and related public health measures. This study will provide representative, standardized, and high-quality evidence to support policy strategy and communications related to prevention measures in Canada and around the world. The inclusion of a low- and middle-income country in this study helps to highlight the disparities between the capacities of different countries to cope with the COVID-19 crisis.",,-99,Université du Québec à Montréal,13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26178,480871,"Developing a Knowledge Translation Plan to Disseminate the ""Long COVID Rehabilitation Strategy"" and ""Long COVID Workforce Toolkit"" across Canada","Evidence now demonstrates that 10-35% of people who contract COVID-19 subsequently experience ""long COVID (LC).""1 This translates to 459,000 to 1.6 million Canadians to date2. Despite this staggering statistic, LC remains underrepresented in public discourse, under-resourced, and lacking provincial and national coordination of services.2-3 Consequently, health and social care providers (HSCPs) involved in LC service delivery have described challenges with staying abreast of LC knowledge and identifying existing resources and supports. Unsurprisingly, this limits their ability to optimize and deliver appropriate services to people with LC (PWLC).1,3 To address this issue, our team collaborated with PWLC, their caregivers, and HSCPs to co-design: (1) a 'LC Rehabilitation Strategy' to address the psychosocial aspects of LC recovery; and (2) a 'LC Workforce Toolkit' to support HSCPs in their various roles. To enhance the impact of this strategy and toolkit, this proposal seeks funding to co-design a knowledge translation (KT) plan for their dissemination.15 We will host five half-day KT consultation workshops to co-design a national dissemination strategy with HSCPs and PWLC. Throughout the workshops, we will identify individual, organizational, and system-level resources and strategies that can enhance the reach and uptake of the rehabilitation strategy and toolkit and maximize their outputs. These outputs will include: (1) provider-facing resources for academic, health, and social care audiences (e.g., communities of practice, care pathways, evidence syntheses); and (2) public-facing KT products (e.g., mixed media education about long COVID, recovery, and support; this might include interactive websites and/or whiteboard videos). We expect that the dissemination of the LC strategy and toolkit will strengthen the health and social care workforce by equipping them with knowledge and supports that enable them carry out and maintain their vital roles in LC care.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",37519.86,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health workforce,2023 +P26179,495218,"The 'Long COVID Education and Awareness Hub': A digitally integrated resource for patients, caregivers, and health care providers","Purpose: Long COVID (LC) is a novel condition impacting 35% of people who contracted the acute COVID-19 virus [1]. Our data supports that living with LC not only impacts one's physical health, it also impacts their psychosocial well-being, creating disruptions in their activities of daily living. The purpose of the proposed project is to co-design and develop an evidence- and experience-informed 'LC Education and Awareness Hub' that addresses the psychosocial needs of LC stakeholders across the continuum of care (including, people with long COVID (PWLC), caregivers (CG), health and social care providers (HSCPs), insurance and disability workers, employers, and members of the public). Relevance: The proposed project aims to increase education and awareness of LC and optimize needed rehabilitation supports across the continuum of health and social care provisions (acute, hospital, in/out-patient, and community-based). Methods and Analysis: 26 stakeholders (n=12 PWLC, n-4 CG and n=10 HSCPs) were recruited to participate in 8 virtual co-design [2] workshops (May to July 2023). During the workshops, participants were engaged in a series of brainstorming, discussion, and consensus-building activities that collaboratively worked towards co-designing the 'LC hub'. Outcome(s): Four key areas were collectively identified as needing to be addressed within the 'LC hub': (1) education, (2) advocacy and public health messaging, (3) health and social care reform and care integration, and (4) peer support. For each key area, meaningful knowledge translation outcomes were identified to be mobilized and disseminated into health and social care practice and policy to better support all stakeholders involved. Conclusion: This research has the potential to raise awareness of LC at a national and international level, identify the network of support needed for LC care provisions, and address the specific needs of LC stakeholders across the continuum of health and social care provisions.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",1481.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Social Workers | Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Approaches to public health interventions | Community engagement | Policy research and interventions,2023 +P26180,497954,"Building Capacity for Older Adult-driven, Neighbourhood Social Programs","In the aftermath of the COVID-19 pandemic, older adults face challenges in social engagement and community participation, aggravated by ageism, program cancellations and isolation. There is a growing demand for initiatives that foster social engagement, skill development, and community involvement among older adults, alongside a lack of information about how best to do so. To address this demand and build knowledge, we aim to explore the processes, impacts, and implications of creating inclusive, neighbourhood-based social programs in equitable partnership with older adults. Insights from ongoing research led by Dr. Carri Hand at the University of Western Ontario highlight inequitable access to social opportunities among older adults, self-directed ageism, and a need for affordable social programming in neighbourhoods, especially for those with mobility challenges. This literature gap and the demonstrated local need provide an ideal opportunity for the current project. Using participatory research, we aim to foster diversity, equity, and inclusion, as well as to understand the socially and historically situated experiences of older adults in two diverse neighbourhoods. The Participatory Process involves planning meetings with older adults interested in program planning and leadership, fostering their capacity to lead. The Implementation of Programs by older adult leaders aims to involve 8-20 diverse older adults for 25 weeks at 1.5 hours per session. This inclusive approach aims to address ageism and other intersecting biases (ableism, racism, classism, sexism, homophobia, and xenophobia). By conducting surveys and interviews, we will refine this innovative model, creating guidelines for similar community programs. This study strives to enhance social participation and inclusion for older adults, contributing to their overall well-being in diverse neighbourhoods.",,-99,University of Western Ontario,798.14,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P26182,474485,COVID-19 Immunologic Antiviral therapy with Omalizumab (CIAO trial) - An Adaptive Phase II Randomized-Controlled Clinical Trial,"Supervisor: Elena Netchiprouk, McGill University The ongoing COVID pandemic, caused by SARS-CoV-2, has resulted in more than 531 million infections and 6.3 million deaths. With the emergence of new variants escaping vaccine-induced immunity, COVID is unlikely to be eradicated. Furthermore, long COVID symptoms affect up to 50% of hospitalized patients and represent another public health threat. Despite unprecedented global research efforts, therapeutic knowledge gaps remain in severe illness and in long-COVID. Current treatments are limited by their side effect profiles and efficacy in new variants such as Omicron. Alternative treatments with dual antiviral and anti-inflammatory properties are required. Omalizumab is an anti-IgE monoclonal antibody approved by Health Canada to treat chronic idiopathic urticaria and asthma. The safety of omalizumab has been extensively demonstrated, particularly in patients with multiple comorbidities such as those seen in hospitalized COVID patients. Omalizumab's antiviral effect has been suggested to stem from enhancing antiviral cytokines. In addition, omalizumab suppresses degranulation of inflammatory cells thought to contribute to the inflammatory response and lung remodelling in severe COVID. Taken together, omalizumab's antiviral and anti-inflammatory properties support the need for a randomized controlled trial comparing omalizumab to placebo in the treatment of COVID. The CIAO trial is a randomized, placebo-controlled trial currently conducted at McGill University, Sunnybrook and Niagara Health Centres that examines the efficacy and safety of a single dose of omalizumab in hospitalized adult COVID patients. The viability of this trial is reflected by consistent recruitment rates and adherence to treatment protocols. By identifying a potentially efficacious treatment for hospitalized COVID patients, this study aims to improve patient survival and reduce the burden of this globally devastating disease on the healthcare system.",,-99,McGill University,110119.22,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2022 +P26183,475843,COVID-19 Immunologic Antiviral therapy with Omalizumab (CIAO trial) - An Adaptive Phase II Randomized-Controlled Clinical Trial,"The ongoing COVID pandemic, caused by SARS-CoV-2, has resulted in more than 531 million infections and 6.3 million deaths. With the emergence of new variants escaping vaccine-induced immunity, COVID is unlikely to be eradicated. Furthermore, long COVID symptoms affect up to 50% of hospitalized patients and represent another public health threat. Despite unprecedented global research efforts, therapeutic knowledge gaps remain in severe illness and in long- COVID. Current treatments are limited by their side effect profiles and efficacy in new variants such as Omicron. Alternative treatments with dual antiviral and anti-inflammatory properties are required. Omalizumab is an anti-IgE monoclonal antibody approved by Health Canada to treat chronic idiopathic urticaria and asthma. The safety of omalizumab has been extensively demonstrated, particularly in patients with multiple comorbidities such as those seen in hospitalized COVID patients. Omalizumab's antiviral effect has been suggested to stem from enhancing antiviral cytokines. In addition, omalizumab suppresses degranulation of inflammatory cells thought to contribute to the inflammatory response and lung remodelling in severe COVID. Taken together, omalizumab's antiviral and anti- inflammatory properties support the need for a randomized controlled trial comparing omalizumab to placebo in the treatment of COVID. The CIAO trial is a randomized, placebo-controlled trial currently conducted at McGill University, Sunnybrook and Niagara Health Centres that examines the efficacy and safety of a single dose of omalizumab in hospitalized adult COVID patients. The viability of this trial is reflected by consistent recruitment rates and adherence to treatment protocols. By identifying a potentially efficacious treatment for hospitalized COVID patients, this study aims to improve patient survival and reduce the burden of this globally devastating disease on the healthcare system.",,-99,McGill University,77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2022 +P26184,468866,"Virtual Primary Care Policy for Pandemic Preparedness and the New Normal: Co-designing resilience, sustainability, quality and equity","The COVID-19 pandemic saw primary care teams across Canada shift rapidly to delivering care virtually. This supported resilience in service provision, and accelerated a trend towards Virtual Primary Care (VPC) that had already started. But it also raised important policy issues about who can access VPC, and whether it is financially viable and of good quality. According to recent measures, the policies surrounding VPC are underdeveloped. To fill this gap our team will co-design, with healthcare professionals, patients, and policy-makers, a VPC policy framework. That framework will provide pragmatic policy options in the areas of: system resilience; financial sustainability; effective delivery of high quality care; optimizing the mix of independent fee-for-service and corporate salaried physicians delivering care; and ensuring access for all Canadians. Before we can create the framework, we need to answer some questions that will require us to look at quantitative data, as well as conduct qualitative interviews and focus groups. The questions we will answer using these methods are: 1. Are there changes to the way health professionals are licensed that might facilitate VPC across provincial boundaries? 2. Which policies might best ensure virtual care billing codes are appropriately updated? 3. Which policies might best support the delivery of high quality care? 4. Which policies might best optimize the mix of independent and corporately provided VPC? 5. How does the pivot to VPC shape access to care for marginalized Canadians? 6. Which policies might best support improving access to VPC for marginalized Canadians? To further help answer these questions, we will share our data with healthcare professionals, patients, and policymakers, inviting them to participate in a consensus-building discussion session. That session will result in a policy framework for decision-makers to use as they prepare for future pandemics and optimize VPC in everyday life.",,-99,University of Calgary,78033.97,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Policy research and interventions | Indirect health impacts | Health service delivery,2022 +P26186,467503,Attachment and Child Health (ATTACH™) Online: Implementation Across Alberta to Promote Healthy Parent-Child Relationships and Mental Health and Development of Children Affected by Early Adversity,"Addressing the impact of early childhood adversity (e.g. family violence, parental depression, low-income) can promote children's mental health and development, giving children the best start in life and reducing societal health inequities. Family violence, depression and low-income undermine parent-child relationship quality linked to mental health and developmental problems in children that tend to persist over the lifespan. Parents' reflective function (RF), i.e. capacity to understand their own and their child's thoughts, feelings, and mental states, can strengthen parent-child relationships, and buffer the negative impacts of early adversity on children. We have developed and tested an effective intervention program called ATTACH (Attachment and Child Health) for parents and their preschool-aged children at-risk from early adversity. In research with 90 families, we found the intervention significantly improved RF, parent-child relationship quality, and children's mental health and development. When COVID-19 prevented in-person intervention at the same time as demand soared for ATTACH, we developed and pilot tested (n=10) an Online Application or ""App"" with our community partners including parents, to deliver the program virtually. With 100 families, we propose to implement and evaluate the ATTACH Online App impacts on: (1a) children's mental health and development, as well as parent-child relationship quality (primary outcome), and parental reflective function immediately and 3 months after intervention, (1b) different patient populations (for whom program works best/worst), and (1c) health professionals' adherence to the clinical intervention protocol. With ~60 knowledge users (patients/parents, health care professionals and administrators), we will examine the feasibility of the ATTACH Online App via: (2a) knowledge users' perceptions and experiences of the App, (2b) App uptake, and (2c) App implementation benefits, facilitators, barriers, and challenges.",,-99,University of Calgary,587871.85,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26189,448820,Indigenous Community Mobilization within the Context of COVID-19: Taking Action Together,"Influenced by evidence-based public health guidelines and recommendations, COVID-19 responses within First Nations communities, where many residents are especially vulnerable to health threats, have been unique. The process of mobilization to keep communities healthy was already underway pre-pandemic, but the pandemic shifted priorities and ways to respond. Communities have turned inwards and enforced strong prevention measures, such as complete community lockdowns and border checkpoints. Interactions with outside health systems have led to some highly publicized incidents of racism. This is a timely opportunity to study Indigenous community mobilization for health in a way that explicitly accounts for Canada's colonial history. This research topic was developed from community interests and concerns. We will use a community engaged approach to research in which community decision making and research involvement are prioritized. Specifically, this project will address the research questions: What are the drivers and impacts related to community mobilization in the context of COVID-19? How can community mobilization for an emergency pandemic response be leveraged to address the long term wholistic health consequences of the pandemic? How has systemic racism, access to care and confidence in science impacted communities' mobilization response to COVID-19? Methods will include document review, Grounded Theory, modified Talking Circles, and In-depth Interviews and will be guided by the social-ecological model and Historical Trauma Theory. Findings from this research will inform the creation or adjustment of ongoing COVID-19 responses and identify levers to supporting trust in public health/science within First Nations communities.",,-99,"Queen's University (Kingston, Ontario)",249754.38,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Policy research and interventions,2021 +P26192,469610,Investigate the immune modulation function of SARS-CoV-2 accessory protein ORF8,"The COVID-19 pandemic has been caused by the highly pathogenic human coronavirus SARS-CoV-2. In addition to the heavy death toll of more than 6 million lives, COVID-19 has disrupted virtually every aspect of social life, and led to astronomical loss in economy. The hallmark of severe COVID-19 disease is the acute respiratory distress syndrome (ARDS) associated with dysregulated immune responses. Human immune system often mounts sequential and regulated innate and adaptive immune responses upon viral infections, which are turned off with infections resolved, thus restoring immune homeostasis. However, SARS-CoV-2 infection has been shown to suppress antiviral interferon response while increase production of proinflammatory cytokines, disrupt the balance of various immune cell subtypes, damage immune cell functions including the antibody dependent cellular cytotoxicity (ADCC) activity. These impacts together cultimate in the detrimental immunopathology seen in severely ill COVID-19 patients. Unfortunately, it is largely unclear how SARS-CoV-2 deteriorates host immune functions, which makes it difficult to develop targeted approaches to restore effective antiviral responses, and cure SARS-CoV-2 infection. The goal of our study is to demonstrate that SARS-CoV-2 exerts systemic effect on host immune cells through its secreted protein ORF8 which is able to act on multiple key immune cells types by interacting with the cell surface Fc receptors and disrupting crucial antiviral immune functions including ADCC. Our study is expected not only to promote the discovery of new therapeutics and prevention strategies to manage SARS-CoV-2 infection, but also to advance our knowledge of coronavirus biology and prepare for future new coronavirus outbreaks and pandemics.",,-99,Lady Davis Institute for Medical Research (Mtl),988193.13,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P26197,478692,Multivalent circular RNA vaccines that are broadly protective against zoonotic betacoronaviruses,"In the past 20 years, three betacoronaviruses thought to have originated in bats have caused devastating diseases in humans. The global pandemic caused by the latest such virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to protect against other strains that could threaten humans to protect against future outbreaks and pandemics. During the COVID-19 pandemic, mRNA vaccines from Moderna and Pfizer/BioNTech provide powerful protection against SARS-CoV-2 and have saved countless lives; however, they are unable to prevent infection and viral transmission due to their ineffectiveness in eliciting robust mucosal immunity. Moreover, these vaccines delivering a single soluble immunogen, i.e., Spike protein, have been shown to only elicit weak or no cross-reactive immune responses, limiting their ability to combat other strains of zoonotic coronaviruses. This proposal seeks to develop a novel multivalent-coronavirus vaccine by leveraging a self-adjuvanted lipid nanoparticle to intranasally deliver circular RNAs encoding multivalent antigens from the SARS-CoV-2 and MERS-CoV that pose a threat to humans. We hypothesize that the proposed technology promises to elicit a broadly protective mucosal immune response against zoonotic betacoronaviruses, which can not only protect the individual but also prevent infection as well as virus transmission. This project will not only help fight the ongoing pandemic but also prevent the re-emergence of these previously existent dangerous pathogens, as well as shed insights to prepare for future zoonotic pathogenic coronavirus outbreaks. Moreover, the knowledge gained from achieving the outlined aims will provide a strong foundation for numerous mucosal vaccine strategies for many pathogens and cancers. The deliverables of this project grant will further encourage the industrial development of RNA vaccines in Canada and help Canadians to respond better to future health emergencies.",,-99,University of Toronto,646929,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV),Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2023 +P26199,475471,Recalibrating Pathological Brain Network Connectivity using Real-time fMRI Neurofeedback among Frontline Healthcare Workers with Post-Traumatic Stress Disorder (PTSD),"Throughout the COVID-19 pandemic, frontline healthcare workers have faced continuous exposure to highly intense and emotional situations, such as witnessing death and suffering. As a result, 1 in 4 Canadian healthcare workers are estimated to have developed symptoms of post-traumatic stress disorder (PTSD) during the pandemic. Further compounding this problem is that the treatments currently offered for PTSD are often ineffective for many patients and may leave up to 40% of healthcare workers with persistent symptoms. Addressing this treatment gap is an urgent societal need as there currently exists immense suffering among the many frontline healthcare workers who have selflessly served Canadians throughout the COVID-19 pandemic. In response to this urgent societal need, a new technology-based approach to PTSD treatment called neurofeedback has emerged as a promising solution. Neurofeedback is a non-invasive brain-computer-interface that allows individuals to search for appropriate cognitive strategies to voluntarily restore healthy brain function and thereby reduce PTSD symptoms. Indeed, early findings have shown neurofeedback to be effective in reducing PTSD symptoms within certain populations (i.e., military members and veterans). However, healthcare workers have endured unique trauma experiences during COVID-19 and the effectiveness of neurofeedback for reducing PTSD symptoms in this population has yet to be studied. Results from this study may inform future clinical trials of neurofeedback and could lead to a novel PTSD treatment for both healthcare workers and other trauma-exposed populations.",,-99,McMaster University,77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2022 +P26200,480675,Real-time fMRI Neurofeedback for PTSD in Frontline Healthcare Workers,"Nearly 1 in 4 frontline healthcare workers in Canada have developed symptoms of post-traumatic stress disorder (PTSD) due to COVID-19-related traumas. Concerningly, gold-standard therapies for PTSD are ineffective for many patients and thus may leave up to 40% of afflicted healthcare workers with persistent symptoms. This exponential increase in PTSD prevalence calls for novel, effective interventions. Neurofeedback is a non-invasive brain-computer interface that trains individuals to self-regulate disrupted functional brain networks linked to mental illness. Unlike other treatments, neurofeedback can normalize pathological brain networks underlying PTSD and is highly effective in reducing symptoms. However, almost all research has involved only PTSD patients who have experienced military or childhood-related traumas. No studies have examined whether neurofeedback would be an effective approach to reducing PTSD symptoms associated with the unique COVID-19-related trauma exposures experienced by healthcare workers. This research will assess the efficacy of fMRI neurofeedback in reducing PTSD symptoms among healthcare workers by regulating pathological brain networks. Specifically, neurofeedback will be used to increase suboptimal ventromedial prefrontal cortex (vmPFC) inhibition on emotion generation (amygdala) and hyperarousal (brainstem) areas. Of primary interest is: i) the association between neurofeedback-mediated changes in brain networks and PTSD symptoms, and ii) the identification of participant clinical profiles and demographic factors that predict neurofeedback success. This research is a timely response to the exponential rise in trauma-related illness among Canadian healthcare workers and may lead to a novel, adjunctive treatment for PTSD.",,-99,McMaster University,13724.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26206,459281,A living evidence approach to variants of concern (VOC) and COVID-19 vaccine effectiveness,"The rapid development of safe and effective COVID-19 vaccines is an outstanding scientific achievement. As an increasing proportion of the world's population is vaccinated, societies have begun to regain some form of normalcy. However, it is evident that COVID-19 will remain a serious public health concern in the coming years, largely driven by variants of concern (VOC - virus mutants with increased spread and/or severity of disease and/or decreased vaccine effectiveness). In many regions the majority of new cases are due to VOC. It is critical to continuously monitor vaccine effectiveness against VOC (e.g., breakthrough infection rates, transmission rates). Systematic surveillance of the rapidly evolving scientific evidence base is necessary to inform public health action and research aimed at improving the use of current vaccines and development of vaccines and/or boosters. Living evidence syntheses use rigorous scientific methods to identify, appraise and summarize evidence, proving their usefulness when the evidence base is rapidly developing and bears significant policy and practice importance. Since April 2021 we have deployed 15 editions of a living review to determine the effects of VOC on vaccine efficacy, regularly communicated to PHAC and HC among others. We will extend this series, also considering additional outcomes such as immunity duration, new emerging VOC and new vaccines. We will search the global peer-reviewed and grey literature daily, update our synopsis weekly, and our full synthesis on at least a monthly basis. We will maintain an up-to-date summary of our findings on our website (including plain language summaries in French and English) and disseminate at least monthly briefings through our networks of decision makers. Our living evidence summaries will ensure that citizens, healthcare and public health professionals and policy makers continue to have access to timely trustworthy evidence to inform their decisions in response to VOCs.",,-99,University of Ottawa,375320.53,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Vaccine design and administration",2021 +P26207,475223,Impact of Post-COVID-19 Condition on the Canadian healthcare workforce: An agent-based modeling approach informed by living evidence syntheses to project long-term impacts on worker recovery and retention,"Long COVID also known as Post-COVID-19 Condition (PCC) affects people's quality of life, social and family life, and multiple aspects of employment. Previous research has shown people with PCC are less productive on the job than before illness, more likely to miss work, and more likely to leave their employer or profession. PCC can significantly impact healthcare workers because they are more likely to be infected with the SARS-CoV-2 virus than the general population. Even more, up to one-half of individuals infected with the virus might develop PCC symptoms such as tiredness or fatigue that interferes with daily life, difficulty breathing or shortness of breath, and difficulty thinking or concentrating. Also, the pandemic has increased staff shortages, disrupted healthcare services (for example, delayed surgeries), and increased stress and burnout among healthcare workers. PCC-related issues and their impact on healthcare workers concern provincial and federal governments because they can lead to long-term strain on the healthcare workforce. We propose research evaluating the long-term health effects of SARS-CoV-2 infection and how those effects might burden the Canadian healthcare workforce. The first component of this research will collect evidence related to PCC outcomes in the working-age population (16 years and older). Next, we will use this information to develop a model that estimates the impact of PCC on the healthcare workforce one year, two years, and five years from now. The impact estimation will include healthcare worker recruitment and retention, labor shortages, and productivity losses. The information from our research will help policymakers better understand and quantify the burdens of PCC on the Canadian healthcare workforce and prioritize related policies to support human resource planning and development.",,-99,University of Ottawa,24075.16,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Disease surveillance & mapping | Post acute and long term health consequences | Indirect health impacts,2022 +P26208,441133,"INSPIRE: INcreasing Students' Pathways to Information, Resilience, and Empowerment","The uncertainties and change due to the COVID-19 global pandemic have worsened the existing mental health strains faced by post-secondary students (PS). PS are already at-risk due to the myriad of stressors related to academic pressure, family expectation, identity development, and role changes. Yet, evidence indicate a further increase of up to 40% in psychological problems in response to the pandemic, thus highlighting the urgent need for mental health and resilience promotion. However, service shortages due to changing guidelines and closures have reduced PS access to programs that may support them in their unique experiences and challenges. The INcreasing Students' Pathways to Information, Resilience, and Empowerment (INSPIRE) Program seeks to address the worsening mental health of PS impacted by the pandemic by building resilience capacity in individuals and communities. My post-doctoral research builds on the Multi-System Model of Resilience (MSMR), a theoretical model I developed and validated across several populations. The MSMR recognizes resilience as an evolving capacity stemming from how well resilience resources are mobilized in response to ongoing needs. My program of research will identify the unique experiences threatening PS mental health within the framework of the MSMR, and develop corresponding intervention strategies following evidence-based approaches. The INSPIRE program will use e-learning platform and gamified activities to build resilience capacities. As part of the planned integrated knowledge translation, an advisory committee will be formed to engage stakeholders in program planning, design, and knowledge dissemination through both novel (e.g., social media, digital storytelling) and traditional (e.g., community forums, conferences, papers) channels. Findings will generate a framework for mental health and resilience intervention program and delivery that can be scaled to extend reach and adapted for other population groups.",,-99,University of Toronto,69221.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P26210,460283,"The COVID-R3ICSAB Study: COVID-19 Wide Impact: Research on the Risk and Resilience In Special Communities of Chinese, South Asian and Black Populations","COVID-19 has disproportionately affected visible minorities in the population, with increased mortality, and major health and socioeconomic consequences with disruptions. Unfortunately most of this information comes from data in the US and UK, as surprisingly Canada has NOT been systematically collecting race based health data! Our COVID-R3ISCSAB team attempted to address this critical knowledge gap in Canada by analyzing COVID-19 health data with previously validated surname algorithm to assign race, and published the analysis for Chinese and South Asian populations with increased death and complications in Ontario. By lobbying governments, the race/ethnicity information is now included in the 2021 Ontario and Alberta health data. Using this new tool, we aim to identify the impact of COVID-19 on racial communities during the 3rd wave and now post-recovery in Ontario and Alberta. We will also analyze the delay in cardiovascular care because of the pandemic, and the impact of Long Covid on the racial minority populations, in comparison to majority white population. Armed with accurate race data and associated risks, we will engage the Chinese, South Asian and Black individual communities, including the medical leaders, community networks and patients, to formulate community specific solutions, gaining in depth insights, to mitigate future COVID waves and emerging pandemics. We will simultaneously work closely with our knowledge mobilization teams, including Public Health and Ministry of Health leadership, together with community leaders and members. This will enhance the resilience of the population, and help to establish a community based Pandemic SWAT team to address future waves and pandemics.",,-99,Ottawa Heart Institute Research Corporation (Ontario),401533.62,Human Populations,Asian | Black | Other,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience","Disease surveillance & mapping | Supportive care, processes of care and management | Post acute and long term health consequences | Approaches to public health interventions | Community engagement",2021 +P26211,460499,Nipah virus induced membrane fusion and IFITM restriction,"Viral infectious diseases pose a great threat to public health and the global economy. The majority are caused by emerging viruses that originated from animals and infect humans. According to a report from the World Health Organization, these viruses are emerging at a rate that has not been seen in the past decade due to population growth and climate change. Therefore, it is urgent to develop intervention strategies against emerging viral diseases. To achieve this, we need to understand the fundamental mechanisms of how viruses infect cells and how the cell intrinsic immunity defense the infection of novel viruses. Many newly emerged viruses are RNA viruses that are coated by a cell-derived, lipid membrane referred to as an envelope. Enveloped viruses enter cells at the cell surface or in endocytic compartments via membrane fusion facilitated by a concerted effort of viral and cellular components. Therefore, membrane fusion has been the target of several intrinsic immune response factors, such as interferon-induced transmembrane proteins (IFITMs), as well as antiviral therapeutics and vaccines. We are investigating how viral and cellular components are recruited and take action at the right place and time to promote and/or inhibit membrane fusion. We will study the entry process of an emerging, deadly paramyxovirus--Nipah virus. We will use super-resolution microscopy to capture the tiny and fast-moving biomolecules on cell membranes and visualize their organization, dynamics, and interactions. In addition, we will use classical mutagenesis, molecular cell biology, and biochemistry tools to elucidate the biological relevance of the single-moleucle organization in virus-induced membrane fusion. This study will provide insights into the fundamental biology of viral entry and inform the design of future antivirals.",,-99,McGill University,527915.71,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P26212,468265,Knockoff statistics-driven interpretable deep learning models for uncovering potential biomarkers for COVID-19 risk prediction,"Canada's healthcare systems have been greatly affected by the coronavirus disease 2019 (COVID-19). Some patients show more severe symptoms of the disease, and thus, need more healthcare resources, while others show mild or even no symptoms. Previous studies have identified several clinical factors, such as age and sex, that are related to this difference. There are also studies examining genetic factors that play important roles in leading to the severity difference. However, these COVID-19 genetic studies did not use enough Canadian patients' information, and their sample sizes are not big enough, which limited the discovery of significant genetic factors for the Canadian population. In this study, we will develop a powerful artificial intelligence (AI) tool to examine which genetic factors are related to the difference of COVID-19 severity using whole-genome sequencing data from a large Canadian COVID-19 cohort. Although AI is a successful technique because of its high accuracy in prediction, it is limited in real clinical practice due to its low interpretability. We will integrate a recently developed statistic method that can handle high-dimensional data and control false discoveries to address the low interpretability issue in the AI tool. This statistic method can provide information about the AI's learning process, thus making the AI model easier to be understood by humans. We will perform a sex-specific genome-wide association (GWA) analysis to explore the potential genetic risk factor for males and females. Finally, we will also build a predictive AI model to predict an individual's risk of developing severe COVID-19 using both the genetic risk score and other known clinical risk factors such as age and gender. The results of this study will help us understand how genetic factors can influence COVID-19 severity and may help us develop better plans for individual COVID-19 treatment, and eventually allocate healthcare resources more efficiently.",,-99,University of Western Ontario,54259.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility,2022 +P26214,500435,Characterizing the role of the periocular mucosa as a site for topical vaccination against respiratory viruses,"The eye is covered by a mucosa constantly exposed to microbes like SARS- CoV-2, more than any other external mucosa (i.e., nose and mouth). Despite this, the eye rarely becomes infected due to powerful immune factors protecting our vision. When the eye is exposed to a microbe, this material migrates into regions that produce immune cells to fight these microbes. These immune cells are distributed in the body to protect against these microbes locally and systemically.In light of the recent pandemic, we need new ways to study how viruses interact with our body and ways to combat them. The accessibility of the eye, and its relationship to the nose and lymph nodes makes this site underutilized to understand how our bodies deal with respiratory viruses. To study this, we will apply to the eyes of mice a coronavirus, Mouse Hepatitis Virus (MHV-1), to understand the immune response to this virus. We will measure immune cells in the eye, nose, and lymph nodes to characterize their interaction within the immune system.Since the eye is a first point of contact for viruses, we propose to characterize how exposing the eye to a virus can protect against respiratory infection. We will use MHV-1 to cause respiratory disease and understand how initial exposure at the eye can shape immediate and long-term immunity. This will form the basis for using the eye as a site for topical immunization. By giving eyedrops containing MHV-1 before the start of respiratory disease, we expect to observe downstream protective effects during respiratory infection.This study will help us understand how the eye shapes our immune system in fighting infections. Moreover, this lays the foundation for a novel and more accessible vaccine approach which may prove more powerful at preventing infection, eyedrops.",,-99,"Queen's University (Kingston, Ontario)",13021.09,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2022 +P26215,448952,Development of a saliva and aptamer based antigen test for variants of concerns of SARS-CoV-2,"Several COVID-19 variants of concern (VoCs) are resulting in both increased transmission rates and reduced vaccine efficacy, giving rise to a third wave of outbreaks. Current rapid tests show low sensitivity, and thus the potential for asymptomatic transmission of VoCs is high. To aid in a return to normalcy, it is critical to put in place rapid, simple and cheap tests that can detect all current and future VoCs. Using Rapid Response Funding from CIHR, our McMaster team has developed a simple saliva-based test using a proprietary DNA aptamer (a DNA sequence that binds proteins) that specifically recognizes the spike protein of the original Wuhan variant of the virus. This aptamer has been fully validated for SARS-CoV-2 virus binding in human saliva, including positive patient samples. Two rapid tests have been created with this aptamer: an electrochemical sensor (like a glucose meter) and a lateral flow device (like a home pregnancy test) for use at home or in congregate settings. An instrument-based assay has also been developed for testing of many people at centralized testing centres. The rapid tests can be completed within 10 minutes and are currently being validated with saliva samples from our local hospitals and assessment centre (currently ~50 positive and ~100 negative samples), with very high clinical sensitivity and specificity. For Phase 2 of test development we will pursue three goals: (1) evaluate >100 current aptamers for binding to UK, South Africa and Brazil variants, and develop new aptamers for any variants for which no current aptamers shows high binding affinity; (2) create an experimental method that allows for rapid generation of new aptamers for future VoCs; (3) work with our clinicians and Canadian industrial partners to fully validate a rapid saliva-based aptamer tests to detect all VoCs using patient samples and finalize the manufacturing and distribution of these tests.",,-99,McMaster University,395995.79,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P26217,468244,Comprehensive RNA-seq profiling of COVID-19 patients: combining microbial diagnostics with host genetic determinants of disease severity,"Nasopharyngeal swabs have become commonplace throughout the COVID-19 pandemic. In order to assess the breadth of information possible from such swabs, a national team of researchers has gathered 66 swabs sequenced with RNA-seq from different patient types (ICU, non-ICU, outpatient, and COVID-19 negative-testing hospital visitors), with more samples currently being collected. I have already incorporated SARS-CoV-2 variant classification, within-host variation in the SARS-CoV-2 population, host gene expression, and microbial coinfections differentiated by patient type into an analysis pipeline (manuscript in preparation). I propose determining host genetic variants from these samples, assessing their importance to COVID-19 disease severity using the many COVID-19 genome-wide association studies already published, and using the unique Canadian HostSeq database to uncover the Canada-wide variant frequencies associated with our samples. This multifaceted approach to data analysis will provide a comprehensive overview of the impact of the COVID-19 pandemic on Canadians, and profile the richness of data attainable from nasopharyngeal swabs.",,-99,University of Waterloo (Ontario),54259.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis",2022 +P26220,481134,SMART (Smallpox vaccine for Mpox Post-Exposure Prophylaxis: A Cluster Randomized Controlled Trial),"It is important to determine how effective smallpox vaccine is in preventing illness in household members exposed to someone with mpox when given after exposure. There are no studies that have compared people vaccinated after such exposure with those who were not vaccinated. The best design to study this is a randomized trial. The Smallpox vaccine for Mpox post-exposure prophylaxis: A cluster Randomized controlled Trial (SMART) is a pragmatic, randomized trial where households will be randomized to either one dose of the Imvamune® smallpox vaccine or to typhoid vaccine which will serve as a control. The objective is to see if the smallpox vaccines reduce confirmed mpox and symptom severity. The study will be conducted in Nigeria. Preparation for this trial has been ongoing for the past six months. The Canadian and Nigerian teams include infectious disease experts, dermatologists, immunologists, public health physicians, biologists, virologists. This research will generate key information about prevention of mpox. It will allow for clinical trial implementation in Africa with immunological testing in Canada, and in so doing will strengthen capacity in Canada to undertake interdisciplinary research on viral zoonotic infections of domestic or global origins.",,-99,McMaster University,375198.56,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",Canada,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase),2023 +P26226,450611,"Addressing the mental health & addiction needs of children and youth during the COVID-19 pandemic: Using real-time community and hospital data to identify, forecast, and meet their needs","Children and youth have suffered stressful and traumatic events during the COVID-19 pandemic and been disproportionately affected by public health mitigation measures. Mental health and addiction (MHA) services must adapt, and require timely information about the needs of children and youth to provide the best possible care during the pandemic and beyond. 1Call1Click.ca is a new initiative of the Kids Come First Health Team to make it easier for children, youth, and families across Eastern Ontario to find the MHA care that's right for them, when they need it. As part of routine intake assessment, 1Call1Click.ca is the only initiative of its kind to capture real-time data on community and hospital-based MHA service needs. We propose to use data from 1Call1Click.ca to identify and predict child and youth MHA needs, so that service providers can tailor their programs accordingly. Our objectives are to: 1.Describe the MHA needs of children and youth contacting 1Call1Click.ca and to identify inequities to accessing appropriate MHA care. 2.Share information about the volume and severity of child and youth MHA with service providers 3.Predict future MHA needs and plan for community and hospital-based MHA services. 4.Determine whether this information helps MHA organizations to tailor their services and meet client needs. We will conduct a 15-month cohort study of children and youth contacting 1Call1Click.ca between May 31, 2021 to Sep 1, 2022 (estimated to be more than 6,000 families). We will use routinely-captured data (demographics, MHA screening tools) from their intake assessment to describe their MHA needs, develop a weekly dashboard to describe service needs, and predict MHA services or the next three and six months. Through this research, we will identify, predict, and address the MHA needs of children and youth during the pandemic and beyond. We have partnerships in place to share our results broadly, to the benefit of chidren, youth, and families across Canada.",,-99,Children's Hospital of Eastern Ontario- Ottawa Children's Treatment Centre,113887.4,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26228,459209,Addressing unmet and emerging health needs of Canadian adults with intellectual and developmental disabilities and their families during COVID-19,"Pre-pandemic, Canadian adults with intellectual and developmental disabilities (IDD) such as Down syndrome or autism had higher rates of mental and physical health problems and were nearly four times more likely to die at a younger age than other adults. COVID-19 has made the challenges already faced by adults with IDD worse, regular activities and contact with family and friends have stopped, there is increased isolation and loss of paid supports, challenges understanding the virus and restrictions, and reduced health care accessibility. Since the onset of COVID-19, our Ontario-based team has been meeting with adults with IDD, families, and service providers to better understand their needs and to find ways to help them. With their input, we developed and trialed six-week virtual groups focused on mental health for adults with IDD, for family caregivers, and for service providers across Canada. This study will build on what we did before by extending the original mental health focus to address emerging pandemic-related health care issues including going to the doctor for a COVID-19 Health Check, vaccination and boosters, managing health problems and medications, diet, sleep and exercise, and returning to regular activities. We will run the three programs twice (Winter 2022, Spring 2022), reaching 440 participants across Canada. Each intervention will include 6 weekly sessions and will teach about health care, with case-based discussions to apply the teaching to their real life situations. Importantly, unlike other programs, our programs will include adults with IDD and family members as educators, alongside health care providers. Participants will complete surveys before, after, and at 3 month follow-up about their health and well-being, what they learned, and their health care (including if they made an appointment for a COVID-19 Health Check), and a smaller group of participants (60) will also talk about their experiences in the program through focus groups.",,-99,Centre for Addiction and Mental Health (Toronto),194340.39,Human Populations,Unspecified,Adults (18 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26232,454863,Co-Creating Vaccine Confidence: An Anishinabe Theatre-based Approach to Strengthen Indigenous Youth and Young Adult Vaccination Support,"A collaborative approach between First Nations communities and the local health care system led to the district of Manitoulin having the highest rate of COVID-19 vaccination uptake in Ontario. But even here, First Nations youth (12 to 18 ) and young adults (19-35) are not highly vaccinated with rates much lower than the middle to older adults categories. We propose to use an interprofessional team of Indigenous performance artists, community, cultural and health leaders who will collaborate with academics medicine, public health approach to better understand this relatively low vaccine uptake among First Nations youth and young adults. Your team consists of an acclaimed Anishinabe Theatre Group, First Nations community leaders, Local COVID-19 Response Planners, Pubic HElath Units, and their collaborative network of First Nations communities in North Eastern Ontario. We will use survey research as well as theatre-based engagement sessions to better understand the lived experience of the pandemic from the perspective of young Indigenous people in our study region, their perspectives, including knowledge, attitude, and acceptance of COVID-19 vaccines. In the next phase of the research, we will build on our learning and co-create, implement and evaluate art and culturally-based intervention to dialogue, educate and promote COVID-19 vaccines. The ultimate goal is to create an online learning resource to build scientific, civic, and media literacy based on Indigenous arts, knowledge, and social sciences.",,-99,Northern Ontario School of Medicine - East Campus,152543.11,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Indigenous People,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P26236,430548,"Gig couriers delivering people, food and packages in a pandemic: Containment strategies to mitigate the occupational and public health impact","Gig courier workers, such as Uber Eats, Amazon Flex, and Lyft drivers, have been busier than ever during the Canadian COVID-19 pandemic as the public attempts to avoid illness by ordering take-away food, shopping online and taking ride-hails rather than public transportation. This places gig courier workers in a unique position to become infected with COVID-19 and transmit it to others as they move people, food and packages from one location to another. Although gig couriers are key vectors between where people live (e.g. homes, care facilities) and the outside world, formal strategies do not exist to protect them from exposure and to mitigate their role in disease transmission. Importantly, this risk is not expected to change anytime soon as the high use of couriers will likely not decline as the economy re-opens. This study will contribute to coronavirus containment strategies by identifying disease transmission risks embedded in gig work contexts and practices, developing clear and tailored interventions for gig courier workers about gig courier disease-related safety and transmission, and widely disseminating results, in live time, as they are identified. Using framework analysis explicitly geared towards generating policy- and practice-orientated findings within limited time periods, we will: document existing courier safety organisational policy; map gig courier worker work, disease exposure and transmission conditions (with attention to gendered dimensions) via social media forums and in-depth interviews with workers and courier firm representatives; and categorise disease transmission risks. Supported by our Strategic Advisory Committee of unions, government municipalities, employers, and vulnerable worker advocates, and using real-time public health communications, this study will create effective national interventions to reduce gig courier disease exposure and protect the public health of Canadians using these courier services.",,-99,University of Waterloo (Ontario),115760.36,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Approaches to public health interventions | Communication,2020 +P26237,443133,"COVID-19 Variant Supplement - Gig couriers delivering people, food and packages in a pandemic: Containment strategies to mitigate the occupational and public health impact","Gig courier workers, such as Uber Eats, Amazon Flex, and Lyft drivers, have been busier than ever during the Canadian COVID-19 pandemic as the public attempts to avoid illness by ordering take-away food, shopping online and taking ride-hails rather than public transportation. This places gig courier workers in a unique position to become infected with COVID-19 and transmit it to others as they move people, food and packages from one location to another. Although gig couriers are key vectors between where people live (e.g. homes, care facilities) and the outside world, formal strategies do not exist to protect them from exposure and to mitigate their role in disease transmission. Importantly, this risk is not expected to change anytime soon as the high use of couriers will likely not decline as the economy re-opens. This study will contribute to coronavirus containment strategies by identifying disease transmission risks embedded in gig work contexts and practices, developing clear and tailored interventions for gig courier workers about gig courier disease-related safety and transmission, and widely disseminating results, in live time, as they are identified. Using framework analysis explicitly geared towards generating policy- and practice-orientated findings within limited time periods, we will: document existing courier safety organisational policy; map gig courier worker work, disease exposure and transmission conditions (with attention to gendered dimensions) via social media forums and in-depth interviews with workers and courier firm representatives; and categorise disease transmission risks. Supported by our Strategic Advisory Committee of unions, government municipalities, employers, and vulnerable worker advocates, and using real-time public health communications, this study will create effective national interventions to reduce gig courier disease exposure and protect the public health of Canadians using these courier services.",,-99,University of Waterloo (Ontario),39124.15,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Community engagement,2021 +P26238,478397,Leveraging an Existing Longitudinal Observational Cohort to Understand the Impacts of Cannabis Legalization and the COVID-19 Pandemic on Alcohol and Cannabis Use in At-risk Young Adults,"Over the last five years, two major societal events have taken place in Canada, the legalization of cannabis for non-medical (recreational) purposes and the coronavirus 2019 (COVID-19) pandemic. The impacts of these events on substance use are continuing to unfold and are not well understood, especially in high-risk groups. One such high-risk group is young adults (20-29), both because the twenties are a highly formative developmental period and the rates of substance use, especially alcohol and cannabis, are highest in this age group. Young adulthood is often when individuals leave the family home, complete formal education, launch careers, and enter marriage and parenthood. As a result, substance misuse during this period can have lifelong impacts by disrupting critical psychosocial milestones. Since 2017, we have been funded by CIHR to follow a cohort of at-risk young adults to understand their substance use. The project has generated numerous findings to date, but has also overlapped with both legalization and the COVID-19 pandemic, thus offering a window into the impacts of these events. Participants in the cohort were ~22 at the start of the study and were ~26 at the last full assessment wave. This proposal is to continue to follow these individuals to ~30 to understand the impacts of these major events. The study will use quantitative assessments to using validated instruments and qualitative interviews to hear participants experiences and perspectives in their own words. In addition, the study will examine differences based on sex/gender and in underrepresented subgoups, such as racialized individuals. The results will substantially contribute to our understanding of the impacts of cannabis legalization and the COVID-19 pandemic, and will inform evidence-based healthcare and policy strategies. Collectively, the project will serve as a high-resolution empirical 'time capsule' to understand the impacts of these momentous events in Canada.",,-99,McMaster University,551296.02,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2023 +P26239,477290,Leveraging an Existing Longitudinal Observational Cohort to Understand the Impacts of Cannabis Legalization and the COVID-19 Pandemic on Alcohol and Cannabis Use in Young Adults,"Over the last five years, two major societal events have taken place in Canada, the legalization of cannabis for non-medical (recreational) purposes and the coronavirus 2019 (COVID-19) pandemic. The impacts of these events on substance use are continuing to unfold and are not well understood, especially in high-risk groups. One such high-risk group is young adults (20-29), both because the rates of substance use, especially alcohol and cannabis, are highest in this age group and the twenties are a highly formative developmental period. Young adulthood is often when individuals leave the family home, complete formal education, launch careers, and enter marriage and parenthood. As a result, substance misuse during this period can have lifelong impacts by disrupting critical psychosocial milestones. Since 2017, we have been funded by CIHR to follow a cohort of young adults to understand their substance use. The project has generated numerous findings on substance use, but has also overlapped with both legalization and the COVID-19 pandemic, thus offering a window into the impacts of these events. Participants in the cohort were ~22 at the start of the study and were ~25 at the last full assessment wave. This proposal is to continue to follow these individuals to ~30 to understand the impacts of these major events. The study will use quantitative assessments to using validated instruments and qualitative interviews to hear participants experiences and perspectives in their own words. In addition, the study will examine differences based on sex/gender and in underrepresented subgoups, such as racialized individuals. The results will substantially contribute to our understanding of the impacts of cannabis legalization and the COVID-19 pandemic, and will inform evidence-based healthcare and policy strategies. Collectively, the project will serve as a high-resolution empirical 'time capsule' to understand the impacts of these momentous events in Canadian young adults.",,-99,McMaster University,73103.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26244,459203,A mixed methods study to understand and promote COVID-19 vaccination among children and youth: the TARGetKids! Study of Children and Families,"Vaccinating children and youth against COVID-19 is essential to resuming essential social and economic activities. Currently, the Pfizer and Moderna COVID-19 vaccines are approved for individuals 12 years of age and older in Canada. Clinical trials for children younger than 12 years of age are underway, and COVID-19 vaccines are expected to be available for children of all ages soon. To date, little is known about vaccine hesitancy for pediatric COVID-19 vaccination. Vaccination decision-making is a complex process influenced by multiple factors. In order to guide the development of strategies to promote equitable COVID-19 vaccine distribution for children, high-quality evidence from a diverse population of children and parents is needed to understand COVID-19 vaccine uptake and hesitancy as well as the factors which influence vaccine decision-making among children, their parents, and primary healthcare providers. In April 2020, we utilized Canada's largest children's primary care research network, The Applied Research Group for Kids (TARGetKids!), to collect COVID-19 related data on children and their parents, including emerging data on COVID-19 vaccination. We now have extensive data on multiple health and well-being measures from children and their parents pre and during the pandemic. We propose to extend this work to understand COVID-19 vaccination among children, youth, their parents, and primary healthcare providers over the next year. With detailed socio-demographic data collected from a diverse population (one in three children participating in the TARGetKids! COVID-19 Study are ethnic minorities), we will provide high-quality evidence to guide the development of strategies to enhance COVID-19 vaccine acceptability, curtail vaccine hesitancy, and promote equitable vaccine distribution.",,-99,Unity Health Toronto,394184.34,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P26246,465813,Impacts of COVID-19 pandemic on diabetes care among South Asian population,"Background COVID-19 and pandemic response measures implemented to limit its spread have resulted in various indirect health impacts due to the disruption of many preventative, diagnostic, and management services. The extent of their impacts on the diabetes care cascade are not known. South Asians, representing 25% of the visible minorities have highest burden of type 2 diabetes. Higher incidence of COVID-19 was reported in neighborhood areas with higher density of South Asian population in British Columbia (BC) and Ontario. However, it is not known if diabetes care cascade among South Asians was impacted more than other population groups. Aims We aim to assess: a) The impact of COVID-19 pandemic on the diabetes care cascade, b) Differential impact in South Asians vs other population groups; c) Patient/provider perceptions of disruption of services. Approach We will use BC COVID-19 Cohort which integrates daily COVID-19 lab tests, case follow-up data, COVID-19 immunizations, hospital and ICU admissions, with demographic, healthcare utilization datasets (medical visits, hospital admissions, emergency room visits, dispensed prescription drugs) Chronic Disease Registry and socioeconomic data and data from BC SPEAK Survey. We will construct care cascade in pre-pandemic years and pandemic/post pandemic years and apply a combination of epidemiological and statistical techniques to investigate the stated aims. We will gather qualitative data based on interviews with diabetes patients and care providers to provide context and inform interventions to prevent further disruptions and optimize care Outcomes: This project will characterize the extent of disruption in services across diabetes care cascade and will identify characteristics of population most affected. We will provide evidence on disparities experienced by South Asians and identify strategies to mitigate the impacts of the COVID-19 pandemic or future similar health emergencies for individuals with diabetes.",,-99,B.C. Centre for Disease Control (Vancouver),84603.63,Human Populations,Asian,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26247,448947,An Automated Molecular Point of Care Testing Device for Rapid Detection of SARS-CoV-2 and New Variants,"Since the beginning of COVID-19 pandemic in March 2020, over 130,000,000 confirmed cases and 3,000,000 deaths have been identified. The shortage of approved low cost rapid diagnostic tests has inhibited the testing of individuals with mild or hidden symptoms, facilitating viral spread the spread of the virus. In this proposal, we gather a team of experts from McGill University, Lady Davis Institute and McGill University Health Centre to address this need. Our team has already developed a testing device for molecular detection of SARS-CoV-2 RNA in a portable and quantifiable fashion with a turnaround time of 10 min. The prototype demonstrate the full cycle of sample preparation (on-chip viral RNA extraction from saliva/nasal swab and amplification) and viral RNA detection via an established RT-LAMP assay. Here, we propose a 1 year modular plan to interface our platform with a smartphone, so that it be easily operated in remote locations, validate our rapid RNA-based testing device with new SARS-CoV-2 variants, B.1.1.7 and 501Y.V2 and to investigate distribution of SARS CoV2 variants in clinical samples. We will also develop an automation approach that can potentially simplify testing of SARS-CoV-2 and new variants in remote locations, making it easier and cheaper to manufacture tests. Our aim is to provide easy access to the results of diagnostics testing in remote locations and avoid overloading hospitals and lab facilities. Overall, the potential to increase COVID-19 testing rate at a low cost will benefit the Canadian health system during the current pandemic and help prevent similar pandemics in the future.",,-99,McGill University,254222.34,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P26252,457604,"Structure, Function, and Broad Neutralization of Emerging SARS-CoV-2 Variant Spikes","The COVID-19 pandemic has had devastating effects on human health, economies, and society. Through international efforts, the global scientific and healthcare community has been able to develop vaccines and therapeutic antibodies at record speeds. Although these technologies have shown promise, the global and rapid emergence of SARS-CoV-2 variants poses a significant threat to their future efficacies. Circulating SARS-CoV-2 variants have demonstrated increased infectivity and resistance to antibodies and vaccines, earning them the title ""Variants of Concern"" or ""Variants of Interest"" by the WHO. More are emerging in real time, and viral evolution will continue as we move to the next phase of this crisis. A defining feature of SARS-CoV-2 variants is the presence of characteristic mutations in spike proteins. The spike protein enables SARS-CoV-2 to infect human cells, which it does by acting as a ""key"" which fits a receptor or ""lock"" on the cell. Spike mutations can increase viral infectivity by changing the spike structure to help it fit the receptor better. Because the spike plays an important role for the virus, it also represents a vulnerability. In fact, the spike is targeted by antibody therapies and is used in vaccines to ""train"" the immune system for recognition. These spike mutations can alter spike structure so that the immune system cannot recognize it, and antibodies cannot bind the spike. My research aims to discover how mutations are affecting variant spikes, provide a structural mechanism for any impacts on receptor binding and antibody evasion, and identify conserved vulnerabilities which allow simultaneous targeting of all variant spikes. Having a structural knowledge of variant spikes is important for updating vaccines to ""re-train"" immune systems for better variant recognition. Identifying common vulnerabilities enables the design of antibodies and therapies that can broadly protect against all emerging SARS-CoV-2 variants.",,-99,University of British Columbia,120892.88,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2021 +P26255,467081,Role of the signalling lymphocytic activation molecule (SLAM)-associated protein (SAP) in the host response and intra-host evolution of SARS-CoV-2,"Since late 2019, the world is dealing with the coronavirus disease-19 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Causing millions of infection cases and deaths, this pandemic has severely impacted the healthcare and economy sectors, among others. With the continuing viral spread and rising cases, novel variants such as the delta B.1.617.2 have emerged with key mutations in structural proteins, conferring the virus to be more infectious compared to the wild type strain. The rise of SARS-CoV-2 variants with such mutations does also raise the concern of reducing the efficacy of existing vaccines, and this has been reported as breakthrough cases. Further, structural mutations in important viral proteins have also been shown to arise in the context of immunodeficient patients with chronic SARS-CoV-2 infection and receiving treatment. Therefore, one objective of our project is to model the genetic evolution of the virus in vivo on immunodeficient deficient mice in presence of antivirals and SARS-CoV-2 antibodies. Mice susceptible to SARS-CoV-2 and knocked out in the signaling lymphocyte activation molecule (SLAM)-associated protein, SAP (K18-hACE2 transgenic/SAP-/-) will be used to model immunodeficiency. This will be followed by sequencing viral samples obtained from these infected immunodeficient mice at different time points. Doing so will provide a basis of tracking how SARS-CoV-2 evolves genetically in the context of immunodeficiency and treatment which could allow to predict those arising in human immunodeficient patients.",,-99,McGill University,13724.56,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2021 +P26258,449021,The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-acquired Pneumonia (REMAP-CAP): Building an International Research Response to Variant COVID-19,"Information about the best treatments for patients with COVID-19 is being generated at a record pace. Large international clinical trials have been central to this process. REMAP-CAP - the Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia - is one such trial; it focuses on the care of the sickest patients, those who are ill enough to need organ support in an intensive care unit (ICU). REMAP-CAP is currently active in 310 sites on 5 continents. It has recruited more than 6150 COVID-19 patients, and identified three treatments that improve patient outcomes - treatment with corticosteroids, inhibition of a protein called IL-6, and blood thinners in some, but not all patients. As COVID-19 continues in Canada and around the world, new variants have become the most common causes. These are infecting younger patients and resulting in more ICU admissions. REMAP-CAP in Canada has exhausted its initial funding; we seek to maintain our leadership role in the international effort to overcome COVID-19. We will direct our attention to understanding treatments for these new variants in three ways. First, we will focus on treatments that seem to be more effective in patients with severe disease, and in particular, on treatments that interfere with interactions between the virus and a protein called ACE2 that the virus uses to enter cells. Second, we will use international variability in rates of variant disease to determine whether the effectiveness of treatment is influenced by the infecting variant. Finally we will work to expand out network of 34 recruiting sites to ensure that we are enrolling patients from across the country, and in particular where rates of infection are highest. In partnership with clinical researchers around the world, we will collaborate to understand how best to care for the sickest Canadians with COVID-19.",,-99,Unity Health Toronto,794444.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase) | Therapeutic trial design,2021 +P26259,480744,The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia (REMAP-CAP): Enshrining a Global Pandemic Research Response to COVID-19 and Beyond,"The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia (REMAP-CAP) is an international clinical trial conceived in Canada a decade ago. It was designed to provide a mechanism to rapidly identify the most effective treatments for severely ill patients during an emerging pandemic. With the COVID-19 pandemic, the trial expanded to 361 hospitals around the world. REMAP-CAP is a platform trial that can study many different treatments at the same time; its design enables new options to be studied as the trial proceeds. We have evaluated 55 different potential treatments, and improved the care of COVID-19 patients by identifying those that are effective (corticosteroids, IL-6 receptor antagonists, heparin in some patients, and antiplatelet agents such as aspirin), ineffective (convalescent plasma, heparin in severely ill patients, interleukin-1 receptor antagonist), and harmful (hydroxychloroquine, angiotensin receptor blockers). To date we have studied 10,000 patients with COVID-19; the trial is ongoing. Our overall goal is to establish REMAP-CAP as a core element of the Canadian response to COVID-19 and future pandemics. This application seeks support to recruit a further 540 Canadian patients, and to expand the network both within Canada and internationally, providing mentorship to new sites and new investigators in resource-limited settings. We will study new therapies that target inflammation, and collaborate with other programs in the Canadian Critical Care Trials Group to study the best supportive care of critically ill COVID-19 patients in the areas of fluid management, and sedation. Finally, we will work with patient and family partners and international colleagues to improve the informed consent process for the trial, and to better understand the ethical dimensions of pandemic research. COVID-19 has brought pain and disruption, but it has also shown what we can accomplish when we collaborate globally.",,-99,Unity Health Toronto,684462.39,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase) | Therapeutic trial design",2022 +P26260,474661,The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia (REMAP-CAP): Enshrining a Global Pandemic Research Response to COVID-19 and Beyond,"The Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia (REMAP-CAP) is an international clinical trial conceived in Canada a decade ago. It was designed to provide a mechanism to rapidly identify the most effective treatments for severely ill patients during an emerging pandemic. With the COVID-19 pandemic, the trial expanded to 361 hospitals around the world. REMAP-CAP is a platform trial that can study many different treatments at the same time; its design enables new options to be studied as the trial proceeds. We have evaluated 55 different potential treatments, and improved the care of COVID-19 patients by identifying those that are effective (corticosteroids, IL-6 receptor antagonists, heparin in some patients, and antiplatelet agents such as aspirin), ineffective (convalescent plasma, heparin in severely ill patients, interleukin-1 receptor antagonist), and harmful (hydroxychloroquine, angiotensin receptor blockers). To date we have studied 10,000 patients with COVID-19; the trial is ongoing. Our overall goal is to establish REMAP-CAP as a core element of the Canadian response to COVID-19 and future pandemics. This application seeks support to recruit a further 540 Canadian patients, and to expand the network both within Canada and internationally, providing mentorship to new sites and new investigators in resource-limited settings. We will study new therapies that target inflammation, and collaborate with other programs in the Canadian Critical Care Trials Group to study the best supportive care of critically ill COVID-19 patients in the areas of fluid management, and sedation. Finally, we will work with patient and family partners and international colleagues to improve the informed consent process for the trial, and to better understand the ethical dimensions of pandemic research. COVID-19 has brought pain and disruption, but it has also shown what we can accomplish when we collaborate globally.",,-99,Unity Health Toronto,2737844.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Clinical trial (unspecified trial phase) | Therapeutic trial design",2022 +P26265,457364,Achieving the quadruple aim: An assessment of a participatory approach to developing individual patient-centred care plans for community-care services,"PHSS Medical and Complex Care in Community (PHSS) is an organization that provides community-care services (e.g., personal support, residential housing, etc.) to people with physical and developmental disabilities and complex medical conditions. PHSS employs a patient-centered, individualized, participatory model of care. For each patient, PHSS creates patient-centred individual service agreements (ISA) and person-centred plans (PCP) through a series of discussions with the patient, and with input from family members, friends, staff, and community members. PHSS used this approach to adapt care delivery during the COVID19 pandemic, and, despite the significantly higher risks within this patient population, to date none of PHSS's patients have contracted COVID19. In this light, upstream interventions, such as the individualized participatory ISA/PCP approach used in the PHSS model of care that have effectively mitigated COVID19 risks for members of the community-care population may also be effective in addressing the health and health service inequities that exist during non-pandemic times. In this project we will interview PHSS patients (or their family) and PHSS staff to understand the key components and impacts of the individualized participatory ISA/PCP approach. We will also interview administrators of health and social care community-care organizations in Southwest Ontario. We will conduct a scoping review to identify types and features of participatory approaches, factors that support or hinder the use of participatory approaches, and evidence of effectiveness and impacts of participatory approaches. We will then create a program logic model by integrating findings from the three studies. The project responds to the urgent need for research on cost-effective upstream innovations in the community-care sector that will improve patient experiences and outcomes and address sector challenges (such as workforce issues).",,-99,University of Western Ontario,78976.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery,2021 +P26266,489843,Dissecting the gustatory and mechanosensory basis of feeding and egg-laying behaviour in disease-vectoring mosquitoes,"Mosquitoes are a critically important threat to public health in Canada and around the globe, transmitting pathogens that cause deadly human disease including malaria, dengue fever, Zika, and West Nile. They transmit these pathogens when they find and bite a human in order to take their blood, using smell to locate a potential victim and their sense of taste and touch to find an optimal place to bite. We believe that it is important to understand the behaviour of these organisms in order to design strategies to improve public health, such as traps and repellents, and that studying sensation in mosquitoes represents a critical opportunity to prevent the spread of disease. In this proposal, we outline a strategy to study taste and touch in mosquitoes taking advantage of the classical laboratory model, the fruit fly, as well as recent technical advances that enable us to directly study the function of genes and neural circuits in the mosquito. Specifically, we aim to identify genes, proteins, and circuits in these animals that are responsible for the taste of salt and the touch of rough texture. Taste and touch show complex interactions as a mosquito navigates its world. For example, salt can be found in human sweat and is an important nutrient on its own, activating many different pathways with dose-dependent positive or negative impacts on feeding behaviour. By contrast, even low levels of salt are a repellent cue for freshwater mosquitoes as they search for places to lay their eggs. In addition to taste, touch guides many different behaviours in mosquitoes, from finding skin and probing for a blood vessel to feed from, to identifying a suitable place to lay eggs. We have previously worked out many of the complexities of taste and touch in the fruit fly, and aim to apply that knowledge to mosquitoes to better understand the similarities and differences between these two organisms. Ultimately, we aim to exploit our findings to prevent mosquitoes from biting humans.",,-99,University of British Columbia,596488.61,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other | Unspecified,,,,,,,,,Zika virus disease | Congenital Zika virus disease | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P26269,449182,Building Capacity for Campus Suicide Prevention: A Policy Practice Partnership,"Post-secondary student mental health is of great concern, with increased rates of anxiety, depression, feelings of isolation, and suicidality observed. The COVID-19 pandemic has exacerbated mental health stressors and concerns about campus suicides, already on the rise. In response, the BC Ministry of Mental Health and Addictions has funded the BC Campus Suicide Prevention Initiative (CSPI), partnering with the Canadian Mental Health Association, BC division (CMHA BC) who will distribute funding and offer technical support to all 25 BC publicly funded post-secondary institutions. This HSIF project will evaluate the implementation and early impacts of the CSPI, identify where further support is needed, and provide recommendations for how the public health system can ensure long-term and sustainable impacts and national scale-up to improve post-secondary suicide prevention and overall mental health and well-being. This study has the following aims: 1. to monitor early outcomes across the CSPI program's implementation; 2. to understand the mediating role of CMHA BC (program administrator and technical support coordinator) in the collaborative processes and outcomes of participating post-secondary institutions; and 3. to assess scalability and sustainability of the CSPI in BC and nationally. An evaluation-based multi-method approach will be used, to thoroughly identify how the CSPI works, for whom, and in what contexts - illustrated through CMO configurations (Contextual conditions, generative Mechanisms, and Outcomes). Qualitative stakeholder interviews, collection of project documents, and observing technical support sessions will inform creation and analysis of data. Ongoing analyses, used to build CMO configurations, will focus on understanding how CSPI implementation operates and with what effect. Findings will be leveraged to directly affect and optimize suicide prevention programs, policies, and resources locally, nationally and internationally.",,-99,"Canadian Mental Health Association (Vancouver, BC)",85055.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26276,430423,Are healthcare workers at higher risk of COVID-19 than other working adults?,"To date, there have been 69,000 confirmed or probable cases of COVID-19 in Canada. Healthcare workers are assumed to be at increased risk of infectious diseases, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2)/CoVID-19 compared to other working adults due to exposure to infective patients. However, no epidemiologic study has examined this assumption. This study is designed to determine incidence of SARS-CoV-2 in HCWs and other, non-healthcare working adults in other frontline service occupations. We will enrol 1640 people working in acute care hospitals (healthcare workers) and 820 people working in non-healthcare jobs from across Canada, including Edmonton, Toronto, Hamilton, Sherbrooke, and Halifax and follow them over 12 months to compare the incidence of SARS-CoV-2 over the 12-month follow-up, risk factors for infection, and several other outcomes in each group. Not only will this allow us to compare and contrast differences in the rates of infection but also in exposures to infective people from all areas of our lives, protective measures taken to reduce infection, and how those measures may affect the risk of infection. We will collaborate with researchers in the US and Puerto Rico, who are collecting similar information on healthcare and non-healthcare workers to determine the similarities and differences between countries and across sites. The results will inform optimal strategies for protecting the workforce, their families, and their patients/patrons.",,-99,Sinai Health System (Toronto),1173054.61,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility,2020 +P26277,443345,COVID-19 Variant Network - Are healthcare workers at higher risk of COVID-19 than other working adults?,"To date, there have been 69,000 confirmed or probable cases of COVID-19 in Canada. Healthcare workers are assumed to be at increased risk of infectious diseases, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2)/CoVID-19 compared to other working adults due to exposure to infective patients. However, no epidemiologic study has examined this assumption. This study is designed to determine incidence of SARS-CoV-2 in HCWs and other, non-healthcare working adults in other frontline service occupations. We will enrol 1640 people working in acute care hospitals (healthcare workers) and 820 people working in non-healthcare jobs from across Canada, including Edmonton, Toronto, Hamilton, Sherbrooke, and Halifax and follow them over 12 months to compare the incidence of SARS-CoV-2 over the 12-month follow-up, risk factors for infection, and several other outcomes in each group. Not only will this allow us to compare and contrast differences in the rates of infection but also in exposures to infective people from all areas of our lives, protective measures taken to reduce infection, and how those measures may affect the risk of infection. We will collaborate with researchers in the US and Puerto Rico, who are collecting similar information on healthcare and non-healthcare workers to determine the similarities and differences between countries and across sites. The results will inform optimal strategies for protecting the workforce, their families, and their patients/patrons.",,-99,Sinai Health System (Toronto),78392.55,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Other,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility | Impact/ effectiveness of control measures,2021 +P26278,460331,Addressing COVID-19 Impacts on Canada's Nursing Workforce,"Nurses form the backbone of health care around the world, yet often face the highest risks in doing their job. Research led by this PI identified high levels of burnout, exhaustion and workplace safety concerns in Canada's nurses prior to COVID-19. Working conditions have worsened, with nurses leaving the profession resulting in a nursing shortage. Workplace changes and new models of care implemented during the pandemic increased workload. While some of the changes were experienced by nurses before during periods of surge, they became constant throughout COVID-19, with little or no break for recovery experienced between pandemic waves. Nursing workloads increased in intensity with each wave, as patients became sicker leading to a nursing workforce that is depleted, fatigued, burned out and leaving. While recent research has identified the anxiety and stress faced by nurses during the pandemic, none has examined ways to mitigate the burnout and turnover occurring now as a result of working through the pandemic. Our study examines nurses' experiences with work during the COVID-19 pandemic, workplace safety concerns, the facilitators and barriers nurses currently face specifically related to their own personal resilience and health behaviours, and identify the supports they need to practice safely during the recovery stages from the pandemic and moving forward. Using a mixed methods approach (survey of nurses, interviews, literature & document review), we will develop policy directions to facilitate effective healthcare work environments that maintain a healthy and resilient workforce for the future. Our study meets all of the funding objectives as it aims to improve understanding of the extent and impact of working through the COVID-19 pandemic on nurse resilience and identify the supports (interventions) needed to practice effectively during the recovery stages from the pandemic, as well as generate evidence from nurses, who experience gendered impacts of COVID-19.",,-99,University of Toronto,213968.31,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +P26281,450616,90Second Parent Well-being (PWB),"Children with developmental disabilities and their parents have been disproportionately impacted by the COVID-19 pandemic. Due to COVID-related shutdowns, many parents did not have access to much needed supports and services and their children's behavior has regressed. The pandemic has taken its toll on the well-being and mental health of parents of children with developmental disabilities, who are already disproportionately impacted by the demands of caring for their children. Parental well-being is an important predictor of child well-being. Subsequently, there is a need for interventions that foster well-being in parents and that support them in their challenging role. We propose an e-health intervention (available via e-mail and text message) to improve the well-being of parents of children with developmental disabilities by giving parents access to brief, easy to understand, and relevant information and strategies, based on evidence-based scientific findings. The intervention is an online health letter 90Second Parent Well-being addressing the many challenges of parenting a child with developmental disabilities. Each health letter will be developed to address a specific issue relevant to parents. Our aim is to develop and test the effectiveness of the 90Second Parent Well-being. In addition to developing an intervention that is accessible and easy to use, we will develop this intervention to be culturally responsive to diverse populations, as these populations are often underserved by current available programming. We will recruit a sample of 273 parents of children aged 3-14 years with developmental disabilities from across Canada. We will measure psychological well-being (primary outcome), parental resilience, depressive and anxiety symptoms (secondary outcomes), as well as demographic information. T-tests will be used to test the effectiveness of the intervention. If effective, we will work with partners to make it widely available.",,-99,IWK Health Centre (Halifax),121550.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26286,488193,Developing cultural competency training for app-based peer supporters caring for Canadian public safety personnel,"Public safety personnel (PSP) are routinely exposed to stressful situations, which increase their risk for negative mental health impacts - including anxiety, depression, and post-traumatic stress injuries. The COVID-19 pandemic has worsened many of these stressors and has likely had long-term impacts on their mental health. Despite this, there is a lack of evidence-informed training available for app-based peer supporters on the specific mental health needs of PSP. Building on our existing knowledge, we aim to: (1) Refine and finalize our pre-existing PSP cultural competency framework using data from Canadian PSP collected by the TRRU for a previous CIHR catalyst grant on Canadian PSP; (2) Adapt a virtual trauma-informed educational (at an appropriate level of training) curriculum to educate app-based peer supporters on the specific needs and experiences of Canadian PSP, which will integrate the cultural competency framework; (3) Host these training materials online at no cost for future learners. Quantitative data from our ongoing quantitative survey of the mental health and well-being of Canadian PSP (since 2021) and extensive qualitative interviews of over 60 PSP during the COVID-19 pandemic, along with our identification of factors (including sex, gender, and intersectional identity) influencing PSP mental health, will be leveraged towards building upon the model, key themes, and training materials. The TRRU is well positioned for this project, as our team consists of experts in trauma-related illnesses with experience developing trauma-informed prevention and early intervention efforts for Canadian PSP. Overall, the Canadian PSP workforce is facing a crisis as an increasing number of personnel are considering leaving the profession. Thus, addressing the mental health needs of PSP is critical to ensuring the sustainability of this workforce, and this project will contribute to peer responders' ability to provide culturally responsive support to Canadian PSP.",,-99,McMaster University,72107.33,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26287,488194,Developing cultural competency training for crisis line responders caring for Canadian public safety personnel,"Public safety personnel (PSP) are routinely exposed to stressful situations, which increase their risk for negative mental health impacts - including anxiety, depression, and post-traumatic stress injuries. The COVID-19 pandemic has worsened many of these stressors and has likely had long-term impacts on their mental health. Despite this, there is a lack of evidence-informed training available for crisis line responders on the specific mental health needs of PSP. Building on our existing knowledge, we aim to: (1) Refine and finalize our pre-existing PSP cultural competency framework using data from Canadian PSP collected by the TRRU for a previous CIHR catalyst grant on Canadian PSP; (2) Develop a virtual training course (at an appropriate training level and sensitive to trauma-informed principles of suicide prevention and crisis intervention) to educate crisis line responders on the specific needs and experiences of Canadian PSP and; (3) Host these training materials online at no cost for future learners. Quantitative data from our ongoing survey of the mental health and wellbeing of Canadian PSP (since 2021) and extensive qualitative interviews of 60 PSP between February 2021 and June 2023, along with our identification of factors (including sex, gender, and intersectional identity) influencing PSP mental health, will be leveraged towards building upon the framework, key themes, and training materials. The TRRU is well positioned for this project, as our team consists of experts in trauma-related illnesses with experience developing trauma-informed prevention and early intervention efforts for Canadian PSP. Overall, the Canadian PSP workforce is facing a crisis as an increasing number of personnel are considering leaving the profession. Addressing the mental health needs of PSP is critical to ensuring the sustainability of this workforce, and this project will contribute to crisis line responders' ability to provide culturally responsive support to Canadian PSP.",,-99,McMaster University,72288.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26288,475224,A novel approach to trauma-informed care: Co-designing policies to support healthcare provider mental health,"During the COVID-19 pandemic, healthcare providers (HCPs) have faced challenging and sometimes traumatic situations that have taken a toll on their mental health. Since February 2021, our team has been conducting research on Canadian HCPs and found they are suffering from high rates of posttraumatic stress disorder (PTSD), depression, and anxiety. We have also learned that during the pandemic, many HCPs suffered mental distress as a result of organizational policies and unintended consequences of leadership decisions. These situations not only left many HCPs feeling their organization did not value or care about them, but also were primary contributors to decisions to leave their job. Prior research has found that implementing trauma-informed care (TIC) principles, such as facilitating choice whenever possible and establishing/maintaining trust by providing transparency via engaging HCP representation in the decision-making process in healthcare organizations, has a positive impact on the mental health of the healthcare providers who work there. This study aims to develop a trauma-informed policy for leaders who work in Canadian healthcare organizations based on an innovative approach to health policy analysis and informed by the Sanctuary Model of Trauma-Informed Organizational Change. Frontline healthcare providers, leaders in middle management and senior management positions from both an acute care hospital and a long-term care facility will be asked to be part of this study. All participants will take part in an interview and/or focus group and complete a survey about their beliefs on trauma-informed care. The results of this study will inform policies that guide leaders to better support the mental health of our Canadian healthcare providers. Efforts to better support and retain our healthcare workforce will ultimately benefit patients and the greater public who depend on their service and well-resourced health care system.",,-99,McMaster University,54826.86,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2022 +P26289,448812,"An Indigenous-led response to COVID-19 that supports communities responding to challenges such as vaccine hesitancy, unique variants and any long-term impacts of Covid into the future.","COVID-19 has now resulted in 139,489,426 cases and 2,993,200 deaths worldwide. Impacts have particularly affected Indigenous, Black and other people of colour and revealed underlying systemic health and social inequities. In this country, Indigenous people are more likely to test positive, be hospitalized and die from Covid than other Canadians. They are also more likely to be vaccine hesitant, reflecting longstanding harms by and suspicions of medical science and the government. This proposed work builds on the activities of our Indigenous-led Kitatipithitamak Mithwayawin project as we work with Indigenous communities across Canada as they respond to Covid. Over the last year, we have built a social network of >2,300 followers on our project Facebook page. This network reflects the impacts of our ongoing communications and outreach (total >150,000 views) and the recent release of our digital App (Indigenous COVID-19). The App will be used by Indigenous communities across the country to provide local, holistic and community-controlled health data in real-time. In this proposal, we will use the App to further our work in 15 Indigenous communities across Canada and complement these activities with additional surveys and interviews. This work is grounded in both public health and in local cultural traditions. It will focus on vaccine and vaccine hesitancy in communities. Importantly, it will also assess any impacts of new variants, better serve ""long-haulers"" that continue to suffer adverse impacts, and assess what effects any pre-existing health conditions have on recovery. The data will be owned and controlled by each community and will help support local health directors. They will also help inform our own Covid-related communications, which will in turn help build community confidence in and uptake of public health measures. In so doing we will support communities as they recover from Covid and navigate an uncertain post-Covid future together.",,-99,University of Manitoba,318508.82,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P26293,475157,Repairing the nursing workforce: Creating compassionate communities and enabling environments to enhance retention and return to work.,"The COVID-19 pandemic has had an enormous impact on the mental heath and wellbeing of nurses with significantly rising levels of distress and burnout at work. In addition, there is a growing exodus of nurses from the healthcare system during the pandemic which has created a critical and unsustainable situation requiring immediate intervention. Based on the timely research our team has conducted on the causes of health worker burnout during the pandemic, we have an enhanced understanding of some promising practices and evidence-based strategies to assist in creating policy that will support compassionate communities and enabling environments to enhance retention and return to work. This project will provide specific policy directions to address the health workforce crisis unfolding across Canada by providing evidence-based solutions and strategies to enhance the wellbeing of nurses in the system and wishing to return to the system - specifically through the designing of compassionate communities and enabling environments to enhance retention and return to work. This proposed study will use both nurses' storied accounts of their experiences of workplace supports in collaboration with national nursing stakeholders to develop policy that will help repair the nursing workforce.",,-99,University of Ottawa,78769.7,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2022 +P26294,468883,Modernizing and Strengthening Communication Core Competencies for Public Health Professionals to Transform Canadian Public Health Practice,"Communication is at the core of effective public health practice. To ensure the public health workforce is appropriately knowledgeable and skilled in communication they should meet a set of competencies set out by the Public Health Agency of Canada. The pandemic and subsequent public health reports highlight the importance of communication in public health contexts. In turn, these show the public health workforces' competencies in the practice of communication are essential. Little is known about how current and future Canadian public health professionals are trained in communication and the extent to which this training aligns with core competencies. In addition, the communication core competencies have remained the same for many years despite many changes in public health and communication, especially as we move through and past the current COVID-19 pandemic. To address these challenges, our research team will determine: how public health training in Canada supports communication competence of the current and future public health workforce; and what evidence and experts show to be new, stronger communication competencies for public health. Together, this information will help address the gaps highlighted in the Chief Public Health Officer Annual Report.",,-99,University of Guelph,78410.34,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Communication,2022 +P26297,476383,Immersive virtual reality exergames to promote the health and well-being of older adults: a mixed methods feasibility study,"As life expectancy continues to increase globally, so does the number of age-related physical, mental, and social challenges. Despite strong evidence supporting the physical and mental health benefits of physical activity, few older adults meet the recommended physical activity levels. Older adults' physical inactivity has been further worsened with the public health restrictions, including the closure of exercise facilities, due to the COVID-19 pandemic. However, the COVID-19 pandemic provided an opportunity to use innovative technologies in the creating of at home exercise opportunities for older adults. My doctoral research investigates how technology can increase older adults' physical activity at home, especially when access to in-person exercise programs and support is limited. To do so, I use both quantitative and qualitative methods to explore how virtual reality games can encourage at-home physical activity in older adults and benefit their health and well-being. The result of my research will provide critical information on developing and evaluating innovative technological strategies for promoting older adults' physical activity during the COVID-19 pandemic and beyond.",,-99,University of Waterloo (Ontario),547.66,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P26304,468243,Contribution of Predicted High-Impact Genetic Variants in Multi-system Inflammatory Syndrome in Children & Adolescents (MIS-C),"Approximately four to six weeks after infection by SARS-CoV-2, some children (316 per 1000000) presented a multisystem inflammatory syndrome with features of Kawasaki disease. While the condition can be considered rare, it is very severe in clinical impact, including fever, which is variably accompanied by a rash, conjunctival injection, gastrointestinal symptoms, shock, myocardial dysfunction and coronary arterial dilation. This condition has been named Multisystem inflammatory syndrome in children (MIS-C), and while the incidence of COVID-19 is lower in children, the infection can still trigger worrying consequences. The genetic risk factors that may contribute to MIS-C presentation are still unresolved. We plan to use data from the HostSeq initiative, which includes the whole genome sequence of thousands of Canadians infected by SARS-CoV-2 who have been severely impacted. This Hostseq databank, which includes detailed clinical information and corresponding whole genome sequences will enable testing for the correlation of specific genetic variants with clinical outcomes. Building from my own expertise in statistical genetics, and from our team's role in developing the HostSeq resource, I will implement the quality control, and population structure components, and examine for rare (<1% population frequency) ""damaging"" genetic variants that are exclusive in the MIS-C positive patients. The rare variants will be identified as potential pathogenicity according to the American College of Medical Genetics and American College of Pathologist (ACMG/AMP) guidelines. In this way, I expect to identify rare damaging variants that were shared by affected subjects possibly similar biological pathways. Having such data may contribute to revealing the genetic susceptibilities that predispose patients to MIS-C, which not only could improve the care and outcomes of this emerging condition, but also increase the understanding of the underlying disorders of immune dysregulation.",,-99,Hospital for Sick Children (Toronto),54259.11,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P26305,469976,Viral innate immunity in S. cerevisiae,"Viruses infect all known forms of life, including single celled organisms such as bacteria and yeasts. While studies of viruses in bacteria have led to remarkable advances for basic research such as the discovery of CRISPR, single-celled eukaryotic organisms have been comparatively silent on this topic. We have discovered a new anti-viral mechanism in the budding yeast Saccharomyces cerevisiae. This mechanism employs a protein called Nuc1, which is homologous to endonuclease G (endoG), a protein family found in all eukaryotic organisms, and even in bacteria. Nuc1, like endoG, resides within the cells mitochondria, a known hub of viral innate immunity in humans. Through our studies of Nuc1, we have discovered that the yeast ""L-A"" virus causes lethal pathogenesis when it is left unchecked in cells lacking Nuc1. We have exploited this lethal consequence of the L-A virus to discover new factors controlling viral repression. Intriguingly, human homologs of some of these factors attenuate SARS-Cov-2, though their mechanism remains unknown. This work exploits the unparalleled power of yeast as an experimental model to investigate these new viral repression mechanisms.",,-99,University of Toronto,574735.47,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Disease models,2022 +P26306,481311,Exploring the relationship of COVID-19-related stressors and depression subtypes among Canadian aging populations: A longitudinal followed a national cohort,"Depression is a growing public health issue as the population aged 65 and older rapidly increases worldwide. The clinical heterogeneity of depression substantively hampers the development of etiology, diagnosis, treatment, and care. The prevalence of depression has dramatically increased in Canada and elsewhere since the outbreak of the pandemic. There is increasing recognition of the need to understand the psychological impact of Covid-19-related stressors on depression. However, to our knowledge, little is known about how Covid-19-related stressors influence depression subtypes. Additionally, because depressive symptoms vary from time to time, it is crucial to identify how depression subtypes change before and after the outbreak of the Covid-19 pandemic and whether the stability of depression subtypes is linked with exposure to Covid-19-related stressors. The study aims to understand the relationships between COVID-19-related stressors and depression subtypes in a national cohort of community-based middle-aged and older adults. The findings of the study will help to understand how Covid-19-related experiences influence different kinds of depression.",,-99,CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital,51762.99,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26307,488607,Imaging Generalized and Selective Markers of Presynaptic Density In Persistent Depression With/Without Other Neuropsychiatric Symptoms After COVID-19,"After people recover from short term breathing problems, and feelings of sickness with COVID-19, there can be longer term problems affecting the brain like clinical depression. Little is known about how COVID-19 leads to symptoms of depression, including trouble with enjoying things, low motivation, slower movement and reduced concentration; because most brain studies are of those who died in the midst of breathing problems from COVID-19, not later when these symptoms occur. Using brain imaging, we recently discovered inflammation in regions that participate in feeling enjoyment, motivation and movement speed. Inflammation is how the cells in the body respond to infection and trauma, like the redness on the skin after a scrape. Cells that make inflammation in the brain can remove connections between cells, or damage connections between cells so we would like to study whether the connections between cells are reduced in the brain regions where there is more prominent inflammation. To do this we propose two imaging methods, one to measure connections of cells that release a chemical called dopamine, and one that looks at lots of connections between cells. We expect a reduction in connections in those with depression after COVID-19 and that those with the greatest severity of symptoms will have the largest reduction in connections. Presently there are no evidence based treatments for depression after COVID-19. The expected results of this study will be important for cure because if connections between cells are missing in people with depression after COVID-19, there are medication treatments that can be repurposed to increase the density of connections between cells. There are also treatments that can make some types of connections better able to release neurochemicals to compensate for lost connections. If the study shows the expected results both of these approaches could be tested as the next step in clinical trials, justified by the imaging findings.",,-99,Centre for Addiction and Mental Health (Toronto),1035414.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2023 +P26310,473329,Unravelling the role of IgA during respiratory virus infections,"IgA is the major type of antibody found in our lungs, and the second most prevalent antibody found in blood. Despite this, the role played by IgA in mediating protection against respiratory virus infections is poorly understood. IgA, like other antibodies, can protect against viral infections in two ways. First, IgA can neutralize virus and prevent it from entering host cells. In addition, IgA bound to virus and/or virus-infected cells can be recognized by specific receptors found of the surface of certain immune cells. Upon recognition, these immune cells become stimulated to eliminate virus and virally infected cells. Mice do not naturally express receptors that recognize IgA. This has been a major barrier to understanding how interactions between IgA and immune cells contribute to protection from viral infections. Using a new mouse model that expresses the human IgA receptor (CD89), we will determine the contribution of IgA to protection against influenza virus and SARS-CoV-2. These studies will critical information that will contribute to the development of new antibody-based therapeutics and better vaccines.",,-99,McMaster University,76662.06,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2022 +P26311,484190,Unraveling the role of IgA during respiratory virus infections,"IgA is the major type of antibody found in our lungs, and the second most prevalent antibody found in blood. Despite this, the role played by IgA in mediating protection against respiratory virus infections is poorly understood. IgA, like other antibodies, can protect against viral infections in two ways. First, IgA can neutralize virus and prevent it from entering host cells. In addition, IgA bound to virus and/or virus-infected cells can be recognized by specific receptors found of the surface of certain immune cells. Upon recognition, these immune cells become stimulated to eliminate virus and virally infected cells. Mice do not naturally express receptors that recognize IgA. This has been a major barrier to understanding how interactions between IgA and immune cells contribute to protection from viral infections. Using a new mouse model that expresses the human IgA receptor (CD89), we will determine the contribution of IgA to protection against influenza virus and SARS-CoV-2. These studies will critical information that will contribute to the development of new antibody-based therapeutics and better vaccines.",,-99,McMaster University,73535.55,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2023 +P26312,489477,Unraveling the role of IgA during respiratory virus infections,"IgA is the major type of antibody found in our lungs, and the second most prevalent antibody found in blood. Despite this, the role played by IgA in mediating protection against respiratory virus infections is poorly understood. IgA, like other antibodies, can protect against viral infections in two ways. First, IgA can neutralize virus and prevent it from entering host cells. In addition, IgA bound to virus and/or virus-infected cells can be recognized by specific receptors found of the surface of certain immune cells. Upon recognition, these immune cells become stimulated to eliminate virus and virally infected cells. Mice do not naturally express receptors that recognize IgA. This has been a major barrier to understanding how interactions between IgA and immune cells contribute to protection from viral infections. Using a new mouse model that expresses the human IgA receptor (CD89), we will determine the contribution of IgA to protection against influenza virus and SARS-CoV-2. These studies will generate knowledge that will contribute to the development of new antibody-based therapeutics and better vaccines.",,-99,McMaster University,672456.5,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2023 +P26315,443347,"COVID-19 Variant Network - Evaluating the differential impact of what we have done, as we prioritize what to do next: a multi-provincial intervention modeling study using population-based data","In Canada, as elsewhere, the COVID-19 epidemic has spread at varying speeds and amplitudes across people, places, and time. Early model predictions were dire across the board largely because of limited local data. So early models had to assume that we were all at equal risk, regardless of conditions that can lead to differential risks of transmission (e.g. living in shelters or long-term care facilities) and of severe outcomes (e.g. age, health conditions). Thus, an assumption of homogeneity was at the heart of the ""hammer"" part of the public health response. Public health measures (interventions) also varied between provinces. As we enter the ""dance"" phase and prepare for future waves of the epidemic, we have an opportunity to be more specific with our interventions if we can quickly learn from how well our public health measures worked or did not work for different subgroups and between provinces, using the wealth of data now available. Our team will use an integrated surveillance and health-administrative data infrastructure and mathematical models that were built over the last 2 months in Québec, Ontario, Manitoba, Alberta, and British Columbia to answer the following questions: 1. Who, where, when, and under what conditions are subsets of the population most at risk? 2. What led to differences in the trajectory and size of COVID-19 sub-epidemics within and between provinces? 3. What types of population- and facility-specific strategies that could stop these sub-epidemics and prevent their re-emergence, while allowing us to relax universal physical distancing measures? Our team of epidemiologists, mathematical modelers, statisticians, clinicians, microbiologists, and public health officials will work together to rapidly provide answers in way that embraces data-driven heterogeneity in risks so that we can better inform decisions on what to implement, when, for whom, and for how long, to minimize the need for universal stay-at-home strategies.",,-99,"St. Michael's Hospital (Toronto, Ontario)",78392.55,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Policy research and interventions,2021 +P26317,469588,Investigation of the long-term autonomic effects of COVID-19 using multimodal physiological monitoring and neuroimaging,"Since the outbreak of the COVID pandemic a year ago, it has become evident that the effects of the virus are not limited to the respiratory system and that several other organs, including the brain, heart, liver, skin and kidneys can be affected. COVID-19 causes a very wide range of symptoms, including neurological symptoms with some of these symptoms persisting several months after disease onset. Of particular interest are its effects on the brain. To this end, imaging has been used to study the effects of COVID on the brain and the results have suggested that many individuals suffer widespread damage in their brain tissue and that the extent of this damage is usually (but not always) related to the severity of the respiratory symptoms. The mechanisms that cause brain damage are also not understood yet. Importantly, almost all previous studies that have used neuroimaging to study the effects of COVID on the brain have used anatomical images, i.e. they have focused on brain structure. However, investigating the potential effects of COVID on brain function is also of great importance and yields significant potential for complementing anatomical studies. In this context, the main aim of the proposed work is to use neuroimaging to study brain function in COVID survivors. We will collect functional magnetic resonance imaging (fMRI) data both during resting conditions, as well as during inhalation of carbon dioxide and controlled breathing, when subjects will be instructed to breath at a specific rhythm and hold their breath. This will give us the opportunity to directly assess whether the processing of respiratory stimuli in the brain is affected by COVID. We will also collect anatomical images from all subjects and assess whether COVID effects on brain function and structure are related to each other. Besides enhancing our knowledge on the wide range of COVID symptoms, the proposed will contribute towards better, individualized short-term and long-term therapies.",,-99,McGill University,876765.59,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2022 +P26320,460260,COVID-19 and Recurrent Pregnancy Loss: Impact of Deferred Care on Perinatal Outcomes of Socio-Economically Diverse Population,"Recurrent pregnancy loss (RPL), defined as two pregnancy losses before 20 weeks from the last recorded period, occurs in up to 5% of all couples trying to conceive. The complexity of the pregnancy period can dramatically increase if women experience pregnancy loss. The management of RPL involves a multidisciplinary approach to diagnose and treat any potential cause(s) of the recurrent losses and to provide emotional support. Due to the COVID-19 pandemic, the community has been isolating for several months, which comes with significant inherent stress, and has impacted the quality of pregnancy care. The full extent of the pandemic's impact on RPL and comprehensive healthcare needs has yet to be determined. The British Columbia (BC) RPL Clinic is a specialized care centre providing care for RPL patients over the past 15 years. The overall goal of this study is to examine the impact of the deferred care due to the COVID-19 pandemic on the delivery of multidisciplinary care for RPL patients, and assess how to maintain care in periods of social disruption. Using the existing RPL prospective study data (n=650), and linkage with the BC Perinatal Data Registry (BCPDR) that collects data for all births in BC, we will analyze how the pandemic has impacted access to and use of the multidisciplinary RPL care, and pregnancy outcomes in the RPL population. The RPL database will be divided into pre-COVID-19 pandemic phase (March 1, 2018 and February 28, 2020), and COVID-19 pandemic phase (March 1, 2020 and August 31, 2022). Our analysis will identify risk factors for adverse perinatal outcomes and propose tailored interventions for high-risk women (e.g., mandatory in-person visits) in order to reduce the adverse pandemic-related effects. Our findings will offer insight into the impact of the COVID-19 pandemic on reproductive health care, and generate evidence to inform clinical practice and policy concerning RPL management.",,-99,University of British Columbia,183650.79,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26322,485956,COVID-19 mortality prediction among vaccinated non-palliative patients at emergency departments,"The COVID-19 pandemic has placed extraordinary demands on the healthcare system and, at times, created the need to ration resources. Healthcare workers face the problem of efficient and fair allocation of limited resources to save as many lives as possible. In times of crisis, they require criteria based on empirical evidence to direct efforts toward patients who would benefit the most. An accurate mortality prediction model is thus a valuable tool for them. Such a model provides an opportunity for transparent discussion about the goals of care. Many such models were developed during the early days of the pandemic with limited data, and the recent ones were developed without considering the effects of vaccines. Since the start of the vaccination campaign, 47.6% of reported deaths were among unvaccinated patients. So, it is crucial to consider the vaccination status of patients when predicting mortality risk. My goal is to develop a mortality prediction model among vaccinated and non-palliative patients to guide the allocation of scarce resources during any future surge. I propose to develop a model using the Canadian COVID-19 Emergency Department Rapid Response Network database, with more than 198,000 registered patients from 51 Emergency Departments across Canada. I plan to include confirmed COVID-19 patients who presented to the emergency department after December 2021. I will use machine learning techniques to develop and implement a model to be used in emergency departments. Healthcare workers could input information, such as age, sex, symptoms, vitals, comorbidities, and vaccination status, to calculate the patients' mortality risk. Access to the model helps them allocate resources efficiently and fairly and have a transparent discussion about the goals of care.",,-99,"Simon Fraser University (Burnaby, B.C.)",13021.09,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2022 +P26326,445529,"Uptake and gaps in HIV pre-exposure prophylaxis (PrEP) use among HIV-negative gay, bisexual, and other men who have sex with men (gbMSM) in Metro Vancouver, Canada before, during and following COVID-19","Antiretroviral medication taken prior to HIV exposure to prevent infection is known as pre-exposure prophylaxis, or PrEP. Men who have sex with men (MSM) are the most affected HIV risk-group in Canada. In randomized trials, PrEP has been shown to be about 90% effective in preventing HIV infection when taken regularly. In 2018, the BC Ministry of Health, through the BC Centre for Excellence (BC-CfE) in HIV/AIDS, began full public funding for PrEP for individuals at high risk of getting HIV. The initial uptake of PrEP through this program has been very high -- more than 5500 individuals have accessed PrEP through the program as of December 2019. Nearly all (99%) PrEP users through this program are male and most (70%) live in Greater Vancouver. However, the impact of PrEP on the HIV epidemic among MSM will depend on uptake by those most at-risk. Further, behavioural risk compensation (e.g., decreased condom use) may result in higher incidence of other sexually transmitted infections (STIs). The covid-19 pandemic has likely also affected MSM in terms of sexual behaviour and access to essential health services, including PrEP. This study aims to evaluate determinants and trends of initiation of PrEP among of HIV-negative MSM over a four-year period and to compare in incidence of new STIs, including syphilis, chlamydia, and gonorrhea, prior to and after starting PrEP, We also want to understand what are the common characteristics of factors of MSM who meet clinical eligibility criteria for PrEP but whom have never initiated its use. Lastly we wish to examine the impact of Covid-19 on sexual behaviour and PrEP use among MSM in BC. Through our study team's position within the BC-CfE and existing collaborations with government and community agencies, these results will directly influence provincial and national policies regarding PrEP access. Our results will inform health promotion and clinical interventions to support PrEP uptake and adherence among Canadian MSM.",,-99,"St. Paul's Hospital, Vancouver",143000.07,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26327,459545,Canadian children and youth's movement and play during the pandemic,"Early COVID-19 restrictions made leaving the house more challenging -- which meant that Canadian kids were moving less, sleeping more, and spending more time on their phones and tablets. This animated video highlights findings from a large national study on how children and youth's movement and play behaviours changed in response the COVID-19 pandemic and related public health restrictions. During the initial wave of COVID-19, less than 3% of kids were meeting the 24-hour movement guidelines (and only 1.5% of kids living with disabilities). We know that movement and play are crucial to healthy child development. Children and youth who meet movement and play recommendations have better physical and mental health compared with their less active peers. This video suggests that there were immediate collateral consequences of the COVID-19 pandemic on child health and provides recommendations to help kids and their families to preserve and promote health across COVID-19 outbreak. This animated video was created to align with the IHDCYH's strategic research priority 1i, Developmental Origins of Health and Disease through the Lifespan. The COVID-19 pandemic and related restrictions have changed the way that children and youth move and play. Several adult conditions (e.g., cardiometabolic diseases) have known childhood antecedents. There are windows of opportunity to engage in healthy behaviours during childhood and adolescence and build lifelong health-promoting habits. This video praises families for their resiliency during the pandemic. We believe this video informs strategies to mitigate the collateral consequences that the pandemic has had on children and youth health.",,-99,Dalhousie University (Nova Scotia),552.01,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26329,475759,Informing community-based interventions to address unmet overdose prevention and sexual health needs of marginalized women during and beyond COVID-19,"Women sex workers experience severe negative health impacts and are profoundly underserved by traditional systems of healthcare and community supports. Tailored and community-based interventions are needed to address the HIV and Sexually Transmitted Blood Borne Infection (STBBI) and overdose prevention needs of women sex workers, as conventional interventions have low uptake and are often insufficiently equipped to support their unique and gendered needs and realities. Sex workers face heightened barriers to accessing HIV/STI, harm reduction, and overdose prevention services due to structural factors such as stigma, criminalization, and compounding access barriers amid the COVID-19 pandemics. While a substantial proportion of sex workers use drugs, few sex worker-specific overdose prevention services exist. Evidence from the global south suggests that community-led and sex worker (peer) delivered HIV/STI services hold strong promise for advancing sex workers' health equity and are WHO/UNAIDS recommended best practices, few such models have been evaluated in Canada. This research will: 1. Examine patterns and determinants of engagement with peer-led/community-based HIV/STBBI and overdose services and supports; 2. Evaluate impacts of the COVID-19 pandemic on inequities in access and determinants of engagement with HIV/STBBI and overdose services and supports; and 3. Develop a set of 'best practices' for peer-led/community-based interventions to address ongoing overdose and sexual health inequities during and beyond the COVID-19 pandemic. This research builds on and will be nested within the AESHA project (An Evaluation of Sex Workers' Health Access) at the Centre for Gender & Sexual Health Equity (CGSHE) (Funding: CIHR/NIH, PI: Goldenberg, 2020-2025), North America's longest running prospective cohort of >900 women sex workers (trans inclusive) who complete detailed semi-annual questionnaires, voluntary STBBI testing, and a novel COVID-19 supplementary questionnaire.",,-99,"Simon Fraser University (Burnaby, B.C.)",77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sex workers | Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Policy research and interventions | Indirect health impacts,2022 +P26331,495244,Impact of COVID-19 pandemic on treatment for hepatitis B,"This study investigated the impact of the COVID-19 pandemic on the number of individuals who started treatment for hepatitis B from 2020 to 2022. The study evaluated the impact on treatment for hepatitis B in three time periods: June to December 2020, January to December 2021, and January to December 2022. We found that 58 fewer people each month started treatment during June to December 2020, compared to what was expected. This was a decrease of 55.5%, compared to what was expected. In 2021, 50.5% fewer people than expected started treatment, and in 2022, 57.3% fewer people than expected started treatment. Percentage decreases in the number of people starting treatment for hepatitis B were greater for males than females, people under 65 years of age compared to those 65 years or older, and for people who inject drugs compared to those to do not inject drugs. In summary, after the start of the COVID-19 pandemic, the number of people starting treatment for hepatitis B was lower than would have been expected in the absence of the pandemic. The number of people starting treatment for hepatitis B remained lower than expected from 2020 to 2022. The impact of the pandemic on the number of people starting treatment for hepatitis B was greater for males, people under 65 years of age, and people who inject drugs.",,-99,B.C. Centre for Disease Control (Vancouver),1879.1,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26333,484177,Elucidating the molecular mechanism by which bat Interferon Regulatory Factors modulate antiviral responses,"Despite being one in every five mammalian species, bats are an under-studied species. Bats can host different viruses, many that can be transmitted to humans. SARS-CoV-2, the agent of the COVID-19 pandemic, is thought to have emerged in bats, evolved and then transmitted to humans. Bats are exceptional agents of zoonotic transmission - being virus reservoirs, remarkable virus shedders and phylogenetically close to humans. Although bats harbour many different viruses, they rarely show any clinical signs of disease. This is likely because bats and viruses have co-evolved over thousands of years leading to suitable adaptations in the bat immune system. Bats have the ability to produce antiviral molecules called interferons (IFNs) and other conserved components of the innate immune system that form the first line of defence against pathogens. The main aim of our proposal will be to characterize IFN production and signaling in response to viral infection in bats. Our research will specifically study the role of three transcription factors (IRF3, IRF7 and IRF9) that are involved in IFN production and/or signaling. Information from this proposal will be foundational for understanding the molecular mechanism by which bats adapt themselves to a multitude of viruses that can potentially cause future pandemics. Consequently, information from bat-virus immune co-evolution will provide a research framework for understanding human-virus co-evolution for the purpose of prevention, control, and possible eradication of new emerging viruses.",,-99,McMaster University,73535.55,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2023 +P26334,480870,"BioNet 2024, a scientific research conference to bridge the gap between bioinformatics and omics researchers across the diverse fields of health research present in Alberta and Western Canada.","As data becomes more abundant and research focuses from a goal of finding new methods of generating data to a world where interpreting existing data is equally important, the fields of bioinformatics and computational biology continue to become more relevant and necessary. Bioinformatics can be an isolating field and bioinformaticians often do not get the opportunity to network with peers as often as traditional wet lab scientists, especially during the COVID-19 pandemic and associated work from home measures have changed the landscape of how research is conducted across institutions of all levels. BioNet 2024 is an on-site conference that caters to bioinformaticians, computational biologists, omics scientists and relevant end-users to bring this experience and knowledge into a single location. Collaboration and innovation are known to develop from both from formal research settings and informal interactions, our conference aims to provide a space for both over a 3-day event. During this event there are also specific sessions to garner feedback from researchers and trainees individually, providing a safe space for each group to discuss the challenges ongoing in the field and develop potential mitigation strategies or learn from the experiences of colleagues. A poster session also provides ample opportunity for early career trainees to showcase research progress and receive essential feedback to propel their studies forward and find potential pitfalls in research plans before they become significant barriers. Together, the BioNet 2024 conference fills an unmet need as a Western Canada bioinformatics and omics conference and will provide additional value to policy makers as feedback from this event will be integrated into the existing 2023 BioNet Bioinformatics White Paper which will be updated for 2024 at the conclusion of this event.",,-99,University of Lethbridge (Alberta),11255.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Other,,Unspecified,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,,,2023 +P26335,481129,Understanding susceptibility and permissiveness to mpox virus across diverse mammalian species,"Mpox, is a re-emerging disease caused by the mpox virus. Since May 2022, there was a multi-country outbreak of mpox in several regions of the world. Although the disease is transmitted from primarily from animals to humans, regular human-human spread has been recently observed making the transmission more than sporadic. Epidemiologic and molecular evidence indicate that mpox virus is found in animals including squirrels, Gambian pouched rats, dormice, and different species of monkeys. Thus, there is an urgent need to characterize the range of non-human mammalian hosts that could potentially be reservoirs for mpox virus. The main aim of our proposal will be to identify and validate the range of these reservoirs for mpox virus, and to characterize the innate antiviral immune responses of these mammalian species. Our research will specifically elucidate the susceptibility (supporting entry of virus into cells) and the permissiveness (ability to support virus replication) of diverse mammalian species to mpox virus. Information from this proposal will define the animal carriers of the virus and will lay a foundation for the molecular surveillance of mpox virus.",,-99,McMaster University,346683.47,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Research for enhanced understanding of the disease | Investigation of zoonotic transmission & reservoirs,Canada,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2023 +P26336,480796,Establishing Stakeholder Priorities for the Development and Implementation of Strategies to Support Continued Youth & Family Recovery from the COVID-19 Pandemic,"In March 2020 the World Health Organization declared the novel coronavirus causing the COVID-19 disease a global pandemic. Governments in Canada took broad sweeping measures that failed to fully safeguard Canadians. Particularly distressing effects have been documented for Canadian youth and their families. For the past two years our research team has been engaging with youth and families in Canada to build a stakeholder-informed national program of Pandemic Preparedness research, to understand and mitigate the complex impacts of the pandemic on day-to-day life and wellbeing for youth and families living in Canada. However, through the conduction of this work, we have identified critical areas requiring additional study to ensure vital knowledge gaps do not persist in our understanding and management of pandemic impacts for Canadian families. These areas include: 1) ongoing negative impacts of the pandemic on day-to-day life and wellbeing for youth and families and 2) evolving mitigating strategies and solutions for youth and family wellbeing. Our proposed work involves two overlapping and interconnected projects that expand our existing work. First, we will synthesize evidence-informed strategies to mitigate negative impacts of the COVID-19 pandemic on youth and family wellbeing, harnessed from our already funded knowledge synthesis projects, in a consensus process with youth and families, clinicians, knowledge users, and decision makers. Second, we are requesting funds to conduct a national stakeholder meeting to generate and communicate evidence-informed consensus statements on youth and family pandemic recovery informed by youth and family experiences. Our ultimate aim is to partner with diverse youth and families in Canada to understand the evolution of their experiences and needs throughout COVID-19 recovery to co-create solutions that develop and mobilize health research that contributes meaningfully to timely, equitable, and effective responses and recovery.",,-99,Dalhousie University (Nova Scotia),15007.94,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26338,473336,"COHESION Study 2.0: COvid-19, HEalth and Social InteractiOn in Neighbourhoods","The potential causes for decreased well-being, worsening of mental health outcomes, and increasing health inequities under the COVID-19 conditions are multifaceted, given the enormity of the disruption to daily living. Some populations suffer more than others, including teens, older adults, women and racialized communities. It is important to understand and document the pathways linking living conditions - including neighbourhood characteristics and housing conditions -, to mental health and well-being trajectories and inequities, to provide key insights supporting rapid targeted policies and interventions. The COHESION project is a longitudinal study combining individual and living condition data from online questionnaires to explore the role that neighborhood social and physical environments play in mental health and well-being trajectories during the post-pandemic recovery period. In particular, we seek to understand the role of these environments on observed changes in health behaviors, such as daily mobility, sleep, and social contacts. We will further assess how these relations vary by gender, age group, income and education level, ethnic identification, and province. This study uses online questionnaires, smartphone app, geographic information systems and various statistical models to test the hypothesized pathways. The study will help generate high-quality evidence about how neighbourhood and housing environments affect long-term outcomes of mental health and well-being, to support Canada's response efforts and guide post-pandemic recovery. In the context of a pandemic where wait times for mental health services in some places exceed one year, there is an urgent need to find alternatives to meet these needs in a sustainable and comprehensive way. We are among the best-positioned teams in Canada to provide rapid and accurate data on the levers in cities that can positively affect the mental health and well-being of the population.",,-99,CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur,76662.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26340,468985,"A collaborative, One Health approach to zoonotic virus detection and risk assessment at the wildlife-human nexus","Numerous high consequence and emerging viruses of public health importance are zoonotic in origin, resulting from spillover from animals to other species, including humans. The complex interactions between the virus, individual hosts and populations warrant a One Health approach, whereby a multi-disciplinary lens is applied to address complex challenges relating to viruses with pandemic potential. Our team has been screening a range of wildlife species for the presence of SARS-CoV-2 and have identified several deer in Ontario and Quebec with evidence of SARS-CoV-2 infection. Ongoing viral activity in deer may represent a new viral reservoir, and we have shown that deer in Ontario have a highly divergent, or mutated SARS-CoV-2 virus and that deer-to-deer and deer-to-human transmission have occurred. Divergent viruses, or variants have the potential to undermine medical countermeasures such as vaccination and to cause enhanced disease in humans and wildlife. Our objectives as an inter-disciplinary group of collaborators examining virus inter-species spillover are to establish a framework and risk assessment approach for the detection and characterization of zoonotic viruses in wildlife, and to ensure knowledge mobilization and translation through a new initiative, the Wildlife Emerging Pathogen Initiative, or Wild-EPI. To do this, we propose to address key scientific questions around zoonotic virus ecology, epidemiology and biology in wildlife. We will use a One Health approach to identify of SARS-CoV-2 and avian influenza virus in wildlife, determine viral circulation among animals and spill back into humans, and the risk of transmission and disease. The proposed work will provide decision and policy-makers with critical information for timely decision-making for emerging pathogens.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",1055636.57,Animals | Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2022 +P26341,499026,Prevention of zoonotic pathogen spillover at the human-animal interface.,"The primary causes of international outbreaks, public health emergencies of international concern (PHEICs) and pandemics are zoonotic in origin. Recent spillover events (sread from animals to humans) from wildlife triggered outbreaks caused by mpox, Ebola and Marburg viruses, and high consequence coronaviruses (SARS-CoV, SARS-CoV-2, MERS-CoV). Despite the monumental impacts of these viral zoonoses, conventional public health programs rarely focus on the prevention of zoonotic pathogen emergence and spread. In Canada, there are substantial functional gaps in efforts to incorporate animal surveillance (testing of animals) in public health. This partly stems from siloed approaches to training and practice across sectors. We have an important window to develop and apply knowledge to prevent the spillover of highly pathogenic avian influenza virus (HPAI), a leading potential cause for the next pandemic. I propose a plan of work based on a One Health approach that considers how the interconnections between humans, animals and the environment they share to prevent zoonotic pathogen spillover. To this end, I will identify settings and situations at highest risk for zoonotic spillover and strive to understand predisposing factors to identify key control points for surveillance and prevention. I will also address ecosystem stressors (e.g. climate change) as they relate to landscape immunity (or how healthy ecosystems protect us from infections), and will work with decision makers to enable translation through existing and novel instruments for communication and policy. This proposal will fill several longstanding gaps in upstream prevention of viral zoonotic spillover and pandemic prevention and launch new initiatives that will allow us to focus research and policy to keep dangerous pathogens from spreading between animals and humans.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",851777.48,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Animal and environmental research and research on diseases vectors | Infection prevention and control,Animal source and routes of transmission | IPC at the human-animal interface,2023 +P26342,481130,Mpox exposure and transmission at the human-animal interface; a One Health approach to viral ecology,"The World Health Organization ongoing outbreak of mpox a public health emergency of international concern. At least 110 countries have reported over 83,900 cases, triggering an urgent global response to control viral spread. Mpox is a viral zoonosis which can transmit between humans and other animals, raising the possibility of human to animal transmission and the establishment of new animal reservoirs in regions such as Canada, making the control and potential elimination of mpox in areas where the virus did not exist before very difficult. We propose a One Health approach to examine exposure and transmission of mpox between humans and other animals. We will apply an interdisciplinary approach to build Canadian capacity for research and response to emerging zoonotic infections, and to generate knowledge and evidence to inform measures for mitigation through three principal aims. First, we will examine mpox ecology by analyzing human-animal exposure pathways in endemic regions, including Nigeria and Ghana (where mpox is an established pathogen) and Canada, where it is not yet endemic. This will identify potential exposure and transmission points of contact, where we will next focus surveillance efforts in high risk human and animal populations along the exposure pathway by screening high risk hosts and the environments that they share. Finally, we will work with key communities and leaders to apply our findings and ideally prevent inter-species transmission of mpox and other viral zoonoses. Our team discovered the first cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in free ranging Canadian wildlife, and have extensive experience screening over 30 species of Canadian wildlife for SARS-CoV-2. In partnership with colleagues in Ghana and Nigeria, we will expand our approach to address similar challenges around inter-species transmission of mpox on an international scale.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",374453.42,Animals | Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Animal and environmental research and research on diseases vectors,Investigation of zoonotic transmission & reservoirs,Canada,,Animal and environmental research and research on diseases vectors | Infection prevention and control,Animal source and routes of transmission | IPC at the human-animal interface,2023 +P26350,475761,Precarious work as a social determinant affecting Black people's health access and health outcomes during health emergencies: Informing health equity efforts in pandemic recovery and pandemic preparedness,"The COVID-19 pandemic has had widespread and unequal effects. For those who are precariously employed, effects have included reduced work hours and lost incomes. This includes workers in employment that is insecure, low-waged, with little or no benefits, and/or non-unionized. Precarious work is an important yet underexamined determinant negatively affecting the physical and mental health of workers, with potential long-term effects. Occupational hazards, limited access to social and health benefits (including sick days), low incomes, and social isolation are among factors contributing to poor health outcomes. Racialized, women, and immigrant workers are more likely to be employed precariously creating a critical health equity concern. A significant proportion of workers vital to the Canadian economy and health system are employed precariously, including 38 percent of workers in British Columbia. There is a need to understand how the pandemic affected precarious work as a determinant of health. This research will specifically examine how precarious work affected the health of Black people in British Columbia since the start of the COVID-19 pandemic. The Black population faces higher levels of unemployment and precarious work attributable to historical and ongoing barriers. Using interviews to learn from lived experiences and personal circumstances, it will examine how factors such as race, gender, and immigration status uniquely contribute to experiences of workers. The study will inform a broader understanding of the impacts of precarious work on the health of marginalized groups. Outcomes will inform pandemic recovery efforts to build back better by extending opportunities to achieve health equity while preparing for future health crises.",,-99,"Simon Fraser University (Burnaby, B.C.)",77083.46,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26354,446637,CATCO Scale-Up COVID-19 Supplement - Canadian Treatments for COVID-19: SOLIDARITY,"There is a great ongoing need for simple, large randomized clinical trials to answer clinically important questions during this pandemic. Patients, policymakers, and clinicians need answers as to whether therapies are effective from clinical trials that are definitive, valid, and generalizable. With over 20,000 new COVID19 cases per week in Canada and 3 million new cases per week globally, there is still both an urgent need and opportunity to answer these questions through clinical trials designed to investigate differences in mortality. Trials that are simple and scalable are the ones that are informing global clinical practice. Unfortunately, the start of this pandemic led to many small, uncoordinated clinical trials. Given the complexity of establishing or coordinating clinical trial networks, prioritizing interventions, and deciding upon trial design, thousands of small trials were initiated globally, most of which remain either unreported and not sufficiently sized or generalizable to convincingly inform clinical practice. The SOLIDARITY clinical trial was proposed at a World Health Organization (WHO) meeting in Geneva in February 2020, with a globally coordinated Master protocol. SOLIDARITY is a simple, large trial, with only the most necessary baseline and outcome data collected, incorporating adequately powered subgroups for relevant baseline characteristics, specifically region, sex, co-morbidities, and severity of disease. Naming a trial 'SOLIDARITY' is not for an acronym - it is a principle for researchers, funders, and clinicians in working globally to determine the most effective therapies and reduce lives lost. Canada has been instrumental in the design and oversight of the SOLIDARITY trial and have thus far recruited over 1300 patients to CATCO (Canadian Treatments for COVID19) since March 2020, an independently sponsored trial directly contributing data to SOLIDARITY. Its first publication was in the New England Journal of Medicine in late 2020, with a subsequent analysis to be released imminently. In this next phase of CATCO, we will continue to grow our clinical trial network across Canada and contribute to the global knowledge on effective treatments for COVID19. The next four agents in this adaptive trial are artesunate, infliximab, narsoplimab, and imatinib. Canada has emerged, through the work of its clinical experts, scientists, and funders, as a global leader in COVID19 clinical management. Through this proposal, we will continue this leadership, and produce the evidence to inform clinical and health system management. Trials such as CATCO/SOLIDARITY and the COVID Network of Clinical Trials Networks are establishing the foundations of an efficient and durable mechanism to respond to both COVID19 and subsequent unanticipated and anticipated threats to health in the years ahead.",,-99,University of British Columbia,2784684.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Therapeutic trial design,2021 +P26355,424701,Canadian Treatments for COVID-19: SOLIDARITY,"This proposal is for an adaptive, randomized, open-label, controlled clinical trial for the treatment of COVID19, in collaboration with countries around the world, working in solidarity with the World Health Organization. We are currently active in 22 centres across the country, have randomized 70 patients at time of writing across multiple provinces, and are funded for 440 participants through the first rapid response fund from CIHR for coronavirus. This proposal is to expand to 80 sites across the country and enrol thousands of patients, over the course of this and subsequent waves of the COVID19 pandemic over the next 1-2 years. Eligible and consenting hospitalized patients with COVID19 are being randomized to receive either standard-of-care or the study medication plus standard of care. Current approved study arms include: 1. Lopinavir/ritonavir 400mg/100mg PO BID for 14 day plus optimized supportive care, OR 2. Hydroxychloroquine 800mg BID for 1 day then 400mg BID for 10 days plus optimized supportive care, OR 3. Remdesivir 200mg IV on day 1, followed by 100 mg IV daily infusion for 9 days plus optimized supportive care, OR 4. Optimized support care. Inclusion criteria will be: Age = 18 years of age, has laboratory-confirmed SARS-CoV-2 infection, and is admitted to hospital at a participating centre. The primary outcome will be mortality at hospital discharge. CATCO is incorporated into the WHO Solidarity Global Trial, with interim results from many countries being reviewed by an independent Global Data Monitoring and Safety Committee. This Committee will decide how often to conduct interim analyses and when to declare effectiveness, futility, or harm. It is anticipated that many thousand patients will be recruited into this trial, with over 2000 globally at time of writing. The larger the numbers entered, the more accurate the results will be, both for all patients and for targeted subgroups; the numbers that can be entered will depend critically on how large the pandemic becomes. Inclusion criteria will be: Age = 18 years of age, has laboratory-confirmed SARS-CoV-2 infection, and is admitted to hospital at a participating centre. The primary outcome will be mortality at hospital discharge. CATCO is incorporated into the WHO Solidarity Global Trial, with interim results from many countries being reviewed by an independent Global Data Monitoring and Safety Committee. This Committee will decide how often to conduct interim analyses and when to declare effectiveness, futility, or harm. It is anticipated that many thousand patients will be recruited into this trial, with over 2000 globally at time of writing. The larger the numbers entered, the more accurate the results will be, both for all patients and for targeted subgroups; the numbers that can be entered will depend critically on how large the pandemic becomes.",,-99,University of British Columbia,2510685.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +P26357,473816,Lassa Viral Transmission and Immunoprotection: Defective Interfering Particles (DIPs) in Carrier Rodents and Lassa Virus-Infected People,"The World Health Organization lists Lassa virus (LASV) as one of the of top 10 pathogens with high epidemic potential. LASV is currently endemic to West Africa, infecting up to 500,000 people, annually. It causes Lassa fever (LF) with symptoms ranging from malaise/deafness to haemorrhaging through all orifices. LASV can be as dangerous as Ebola and SARS-CoV-2. About 20% of LASV-infected people develop disease that can severely damage the brain, liver, spleen, kidney and other vital organs. Hospital fatality of LF patients can be as high as 69%. But, the reasons why LASV-infected people mount such varying immune responses are not understood. LASV is transmitted to humans mainly through the aerosols of urine/faeces of rodents. As an RNA virus, it has an inaccurate system of replication. 'Errors' in replication can lead to the production of defective interfering viral particles (DIPs) that are known to modulate immune response, in other RNA viruses. DIPs are present in LASV-infected mice, but their relevance in LF in humans is unknown. Therefore, during my Fellowship, I will determine whether (i) DIP levels vary between rodent species and modify transmissibility to humans, and how (ii) DIPs modulate immune responses in LASV-infected people, and regulate disease severity in LF patients. DIPs will be measured in rodent urine, faeces and tissue to understand how individuals in endemic areas are exposed to Lassa antigens. DIPs and antibodies in the patients' blood will be studied to reveal their role in disease progression and immunity. Because DIPs stimulate immune response without causing infection, DIPs are considered as vaccine candidates (e.g., Ebola, SARS-CoV-2, Dengue, Zika). No satisfactory treatment or vaccine is available to fight against LF. Hence, understanding LASV transmission and immunogenicity via a One Health approach, and identifying novel LASV vaccine candidates and diagnostic approaches are of paramount importance to prevent a LF pandemic.",,-99,"Broad Institute of MIT and Harvard (Cambridge, MA)",109655.17,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Arenaviridae,,,,,,,,,Lassa fever,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Belize,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease pathogenesis | Supportive care, processes of care and management",2022 +P26361,460308,Assessing the impact of the COVID-19 pandemic and financial support programs on social inequalities in mental health in Canada,"There is growing evidence that the COVID-19 pandemic, the measures applied to curb its spread, and its coincident economic shock, have had a profound negative impact on population mental health, including sharp increases in anxiety, depression, and substance use. However, few studies have explored the effects of the pandemic among socially vulnerable groups who were disproportionately affected, and the effectiveness of policies implemented to address the economic consequences of the pandemic are unknown. We propose to examine the impacts of the COVID-19 pandemic and attendant policy responses on patterns of mental health and substance use in the Canadian population. This empirical study will use data from a pan-Canadian cohort of adults surveyed in any of the past six waves of the population-representative Canadian Community Health Survey Annual Component, 2015 to 2020. This cohort of roughly 306,000 will be linked to administrative data including mental health and substance use outcomes over the study period from 2015-2020, as well as receipt of COVID-19 financial benefits from tax files. Our specific aims are: Aim 1. To measure the population-level impact of the pandemic nationally, within provinces/territories, and across social groups, as well as whether these effects varied depending on local response measures implemented. Aim 2. To measure the impact of financial support programs, including the Canada Emergency Response Benefit (CERB) program, on mental health and substance use. Aim 3. To evaluate how financial support programs affected social inequalities in mental health and substance use. By capitalizing on rich survey and administrative data, this project will provide a comprehensive pan-Canadian investigation into the mental health impact of the COVID-19 pandemic and interventions implemented, which is critical to enhance preparedness for future health emergencies.",,-99,McGill University,84302.64,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26362,481271,Epidemiological modelling of behavioural impact on Mpox mitigation strategies,"Prior to 2022, the viral disease mpox was largely ignored by the global community. However, once it began to spread to many countries resulting in an ongoing outbreak, it became an international public health emergency. The ongoing outbreak has had a particular impact on the gay, bisexual, and men who have sex with men (gbMSM) community. Although the COVID-19 pandemic taught the world that understanding infectious disease transmission is important, it is equally crucial to analyze the influence of human behaviour in disease dynamics. Reducing the spread of mpox requires understanding how people will respond to information about the disease and how behavioural changes elicited by this response can affect public health strategies. Moreover, the disproportionate impact of mpox in the gbMSM community implies that additional behavioural concerns need to be addressed. In particular, stigmatizing attitudes result in increased hesitancy to access public health assistance by gbMSM individuals while also influencing public opinion of mpox. This project develops an epidemiological model of mpox that includes changes in behaviour. This modelling is driven by data from scientific literature and near real-time behavioural information from social media on prevailing attitudes towards mpox and members of the gbMSM community. The project will create a community advisory board that includes experts and members of the gbMSM community in order to develop culturally sensitive and adequate strategies and ensure timely knowledge translation of our results to a broad audience.",,-99,"Centre de recherche en santé publique (Montreal, Quebec)",309163.62,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes | Ongoing assessment & evaluation of surveillance,Canada,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2023 +P26363,466533,Nokuzola Ncube- CGS-M Application,"Intimate partner violence (IPV) is any form of abuse maintained by an intimate partner with some examples including physical, sexual, emotional, and financial abuse. In response to the COVID-19 pandemic, public health guidelines were quickly implemented to decrease the spread of this highly contagious disease. However, one unintended consequence of stay-at-home orders and physical distancing requirements was an increased risk of IPV exposure and severity for women. Increases in IPV exposure and severity were accompanied by changes in access to mental health services including shifting service delivery from in-person to virtual appointments. There is limited research on the effect of these shifts in mental health services on women who are experiencing IPV in terms of both access and satisfaction with services. As such, the proposed cross-sectional study aims to examine mental health service access and satisfaction during the COVID-19 pandemic amongst women who have experienced IPV/are experiencing IPV in Ontario as measured by(1) the Client Satisfaction Questionnaire (CSQ-8) and (2) the Barriers to Access to Care (BACEv3). To achieve this, 42 women who are experiencing IPV or have experienced IPV in the last 12 months will be recruited through Kijiji. To be eligible for this study, women have to had experienced IPV in the past 12 months during the COVID-19 pandemic, live in Ontario, be over the age of 18, and have access to a safe computer/telephone number. Data analysis will allow to compute measures of central tendency, dispersion, and correlational relationships. Findings from this study aim to inform how various mental health services can best support women who are experiencing intimate partner violence during a pandemic.",,-99,University of Western Ontario,13724.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26367,450629,Assessing the impacts of COVID-19 on routine school-based immunizations and investigating strategies to catch-up on missed immunization opportunities in Canada,"The COVID-19 pandemic has disrupted routine school-based immunization programming across Canada. To what degree, however, remains unknown. Without effective catch-up strategies, these disruptions to programming could severely impact future vaccine-preventable health outcomes. This project will determine the extent of the expected negative health impact of the COVID-19 pandemic as a result of missed school-based immunization in different jurisdictions across Canada. It will also explore to what extent various policies and practices are likely to be able to catch-up on missed immunizations and mitigate those negative impacts.",,-99,University of Saskatchewan,120944.03,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +P26374,473331,"Artificial intelligence assisted Method, Optimizing the Prediction of Patient Outcomes among Long COVID-19 Patients.","COVID19 is a continuing pandemic with several challenges that are now expanding to its lesser known long-term effects. Long COVID19 is a term given to the protracted illness that patients of COVID19 continue to experience even amidst their post recovery phase. Difficulty in breathing, weakness, headache, cough, brain fog, and lack of smell are usual symptoms that are observed in Long COVID19. However, people can also suffer from more severe effects that affect the lungs, the heart, muscles and the brain. There is varied data from across the globe. Our CIHR project grant will be exploring what factors are strongly associated with the Long COVID19 patients needing admission in an intensive care unit, or a patients needing a ventilator? Our project will explore whether any differences exist among male and female patients, among people living in different cities, and among people living in different countries. Literature shows that lung involvement is the main feature of Long COVID19 disease, and data has illustrated that findings from computed tomography scans correlate with the outcome of the disease. Using AI we can identify with increased reliability the CT features that are correlated with poor outcome. This project would allow us to quickly detect the Long COVID19, provide better care for the patients, reduce the burden on care givers, reduce the work load on radiologists, and save health care costs. By using data sets from different countries, we are ensuring that our model is generalizable across many countries. As a secondary objective, we will be creating a telehealth radiology registry for the Northern Health patients whose diagnostic images are read at the Vancouver General Hospital after regular service hours, on weekends, and on stat holidays. The teleradiology service impacts the overall health in the First Nations populations as well as general population. We propose to provide service and evaluate the needs of people in NHA and IHA regions.",,-99,University of British Columbia,76662.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P26376,485977,The mystery of BCG vaccine in protection against SARS-CoV-2,"Years after the beginning of the COVID-19 pandemic, the whole world has been affected. While infection rates have decreased over the years, the beginning of the pandemic still saw exponential increase in global infections, jumpstarting the campaign to design vaccines. While we now have these vaccines available, back then we lacked protection against the virus. The Bacillus Calmette-Guerin (BCG) vaccine is currently widely used in the prevention of tuberculosis, yet its use does not end there. Literature associates BCG with protection against various parasites, fungal infections, and bacterial infections. Its ability to provide such broad protection has been attributed to its induction of trained immunity. The immune system has two arms, adaptive and innate immunity. The innate immune response is the first line of defense and elicits fast, non-specific responses. The adaptive immune response, while slower to respond, acts in a specific manner by building immunological memory of the infectious agent. In trained immunity, innate immune cells appear to gain a memory-like ability and in turn can provide greater protection against different pathogens. Many studies have investigated the protective abilities of BCG against different pathogens with some yielding contradicting results. In fact, recent literature has been split regarding the ability of BCG to provide protection against SARS-CoV-2. An important distinctive factor between these studies is the BCG strain used, and so I hypothesize that BCG-Pasteur contains a unique genomic factor(s) that allows protection against SARS-CoV-2. Investigating the effects of differing BCG vaccine strains (Tice vs. Pasteur) on the immune response could be the key in better understanding the range of protection this vaccine can provide.",,-99,McGill University,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Vaccines research, development and implementation","Supportive care, processes of care and management | Characterisation of vaccine-induced immunity",2022 +P26378,443035,"The CART PREG-Epi Study: Pandemic Reproductive health and health Equity- Guidance from Epidemiology to improve reproductive, perinatal, and maternal mental health and substance use care","From impacted fertility rates due to crisis isolation, intimate partner violence and limited access to contraception, through lesser access to abortion, pre-natal health services, screening for adequate weight gain in virtual visits, and the identification and management of mental health and substance use disorders in pregnancy, the pandemic public health countermeasures and health system adaptations of the COVID-19 pandemic have had unknown and important impacts on the broad range of reproductive health outcomes throughout Canada. Also unknown are important and potentially inequitable impacts on the reproductive health of those among disadvantaged populations. As Public Health policy makers and decision makers leading health systems and services prepare to meet these challenges, data is urgently needed on the unintended effects of the pandemic public health counter measures and the health system responses on the range of reproductive health outcomes and changes to health inequalities. Our cross-jurisdictional, time series study of provincial health administrative data in Ontario, Manitoba and BC, will include targeted qualitative investigations and has engaged strong integrated knowledge translation throughout with key decision makers. Together with the Provincial Public Health Officers and key ministry of health leads in each province, we will compare changes to the range of reproductive health outcomes (both health events (such as pre term birth) and health utilization (such as adequate prenatal care)), before, during and over each six months period through the pandemic. Results will provide vital timely information to nimbly and iteratively inform ongoing pandemic planning, for use now and in future pandemics, to ensure people across Canada have the best reproductive health outcomes.",,-99,University of British Columbia,74711.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26379,479507,Investigating the Mechanisms of Paramyxovirus Assembly: Implications for Antiviral Therapeutic Design,"Paramyxoviruses are a group of highly infectious and potentially lethal human and animal pathogens with pandemic potential. Notable examples of paramyxoviruses include measles and parainfluenza viruses, which affect millions of people each year, and Nipah virus, which is rare, but almost always fatal. Unfortunately, there are currently no treatments available for any paramyxovirus. As viral assembly pathways provide a good target for drug development, our work will focus on characterizing paramyxovirus viral assembly in an effort to identify weak points that could be used for the development of new therapeutics. Paramyxovirus particles are made up of only six structural proteins, among which the matrix protein is of particular importance due to its central role in the assembly and release of new virus particles. When a cell is infected, paramyxoviruses produce many copies of the matrix protein, which then attach to the inner surface of the infected cell membrane to form an interlocking network. This network of matrix proteins helps to assemble new virus particles, which are released from the host cell and go on to infect other individuals. Despite ongoing research efforts, the process of how matrix proteins assemble and how they interact with other components of the virus and the host cell remains poorly understood. Thus, the goal of this research is to understand the underlying structures and processes involved in the formation and release of paramyxovirus particles. We will use a combination of advanced imaging techniques and laboratory experiments to figure out the process of how matrix proteins join together to form the interlocking network and what role membrane lipids play in putting together the virus particles. This research will give us a better understanding of the viral life cycle and will provide a roadmap for the design of new, effective antiviral drugs to protect against these deadly viruses.",,-99,University of Toronto,771744.57,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Paramyxovirdiae,,,,,,,,,Nipah and henipaviral disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P26380,485980,Narratives of Cancer Recovery Pre and Post COVID: A Mixed Methods Comparative Analysis,"The COVID-19 pandemic resulted in significant reductions in access to cancer care services across Canada, including delayed diagnoses, surgeries, and treatments, creating a backlog that continues to impact care. It is well established that leaving treatment and moving into the recovery phase of cancer is often particularly distressing for many people as they deal with fears about cancer returning, changes in identity, and the loss of access to the care and attention of their healthcare team. The proposed study will be the first of its kind to compare narratives from cancer survivors collected at the end treatment both before the pandemic began (fall 2019) and three years following (fall 2023). This information will be collected through short narrative care interviews, designed to provide a supportive way for cancer survivors to process the experience of recovery and find ways to effectively move forward in life. The narratives, as well as data collected through questionnaires assessing mood and well-being, will then be examined for emerging patterns and differences between the before-COVID and during-COVID time periods. Understanding the specific impact that reductions in access to timely diagnosis, treatment, and support have had on cancer survivors will generate new knowledge surrounding the complex needs arising in this medical population, as well as guide the development of future interventions for individuals struggling at the end of treatment. This knowledge can further inform health care providers and cancer care organizations on how to best support Canadians recovering from cancer during this uniquely challenging time in our collective history.",,-99,"York University (Toronto, Ontario)",13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26381,454636,An ethnographic exploration of user engagement in long-term care,"The devastating impact of COVID-19 on older adults in long-term care (LTC) facilities across Canada has drawn public attention to systemic problems across the sector. As governments, researchers and the public contemplate policy reform, there is an urgent need to ensure that residents and family carers can meaningfully engage in policy and service design. User engagement initiatives refer to involving people with lived experience in service or policy development. While some mechanisms to support user engagement in LTC facilities exist, such as resident and family councils, advisory committees, and consumer groups, it is unknown how these forums promote user engagement. My postdoctoral research will address this research gap through an ethnographic study examining how policies and institutional practices facilitate and constrain user engagement in LTC. Using a combination of document analysis, semi-structured interviews, and participant observation, I will explore the extent to which current mechanisms for user engagement enable residents and carers to exercise their rights and influence change. First, I will conduct a document analysis of LTC policies and legislation to examine how residents and their rights are portrayed in document materials. Next, I will interview stakeholders involved in user engagement within LTC, health services and community organizations to examine user engagement practices and constraints. Finally, I will conduct participant observation with family and resident councils in two LTC facilities to explore the experiences of residents and carers attempting to influence change. To enhance the relevancy of the research, the study will be guided by a knowledge user advisory committee made up of residents and carers. This research will support an in-depth understanding of the factors that shape user engagement in LTC and inform the development of user engagement initiatives that promote the rights of residents and family carers.",,-99,University of British Columbia,106618.28,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Health service delivery,2021 +P26382,476398,Resident and Family Engagement in Nursing Homes,"The devastating impacts of COVID-19 on nursing home residents across Canada has drawn public attention to systemic problems and the restricted rights and freedoms of citizens residing in nursing homes. As governments, researchers and the public contemplate nursing home policy reform, there is an urgent need to ensure that residents and family carers can meaningfully engage in policy and service design. User engagement initiatives, which broadly refer to involving people with lived experience in service or policy development, have gained prominence in the health sector to promote quality improvement and democratic processes. In nursing home settings, resident and/or family councils are commonly required as a mechanism for engaging service users. However, little known about these forums, or the extent to which they enable residents and families to influence program or policy changes. My postdoctoral research will address this gap through a comparative ethnographic study of user engagement in nursing homes in two Canadian provinces (British Columbia and Manitoba). Using a combination of document analysis, participant observation and interviews, the purpose of this study is to explore whether and how resident and family councils enable residents and family carers to assert their rights and engage in decision-making processes, and to identify strategies to enhance user engagement in nursing homes.",,-99,University of British Columbia,873.61,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Health service delivery,2022 +P26384,495160,Using synthetic virology approaches to elucidate novel virus-host interactions and develop targeted therapeutics,"The central theme of my research program will study poxvirus-host cellular interactions to develop effective and more personalized biotherapeutics (vaccines and oncolytic viruses [OVs]) towards cancers and infectious diseases using synthetic virology approaches. I am interested in harnessing the power of these technologies to study how cellular antiviral responses are differentially induced in various cell types during poxvirus infections. I am also interested in the relationship between nucleic acid sensing pathways and other poxvirus biological processes (like transcription, replication, and recombination). I plan to extend these studies to investigate the role of known and unknown viral antagonists of nucleic acid sensing on these processes. I will use my skills in rapidly generating recombinant poxviruses using synthetic biology technologies to discover what makes viruses able to replicate efficiently in some cell types, and not others. Understanding why poxviruses preferentially replicate in certain cell types or species will enhance their utility as cancer therapeutics. Results from these basic molecular virology studies will inform my studies on generating more potent OVs, whether alone, or in combination with other treatment modalities, like adoptive cell therapies, radiation, or in combination with OVs from unrelated virus families. I am also interested in whether these modified viruses can be used as vaccines to increase the magnitude and durability of an immune response to emerging/re-emerging viruses, including monkeypox virus and SARS-CoV-2.",,-99,University of Alberta,2222.03,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Poxviridae,,,,,,,,,COVID-19 | Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics",Research for enhanced understanding of the disease,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P26387,473885,Predicting the Optimal Clinical Dosing Regimen for Promising COVID-19 Drugs,N/A,,-99,University of Manchester (England),4709.17,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Europe,Unspecified,,,,United Kingdom,,"Therapeutics research, development and implementation",,2022 +P26389,485645,Improving Public Awareness and Driving Multi-level Action on the Causes of Poverty to Support Financial Wellbeing,"Due to the COVID-19 pandemic, more people are having difficulties in covering day-to-day expenses, saving money and paying down debts. Financial struggles make adults and children ill, physically and mentally. Women, seniors, Black people, Indigenous peoples, and immigrants have struggled more than anyone else. It is time for us to look beyond what people can learn to manage their finances better. We need to look at the causes of their financial problems (e.g., lack of job training; no affordable childcare facilities). Public health is well positioned to make a contribution to this topic. It can present solutions that address the causes and consequences of financial struggles and create fair, equitable chances for everyone to enjoy financial stability. Our team did that. With funding from CIHR, an international group of researchers, practitioners, policymakers, and stakeholders developed two resources to support organizations and governments to act on financial wellbeing. Since the release in 2022, we have delivered some presentations to introduce those two resources. The current funding opportunity will support our team to share important information with the general public about the importance of financial wellbeing for health. The objectives of the proposed Café: 1) increase awareness about how financial wellbeing impacts health; 2) talk about addressing the root causes of financial struggles and why we need to act quickly to meet the needs of people from all walks of life; 3) share the resources we developed; 4) discuss key learnings from the work that Alberta Health Services is doing to reduce the impact of financial strain; and 5) provide an opportunity for the general public to dialogue with researchers, decision-makers, and organizational partners about the causes and consequences of poor financial wellbeing. Participants will leave the Café more aware and equipped to discuss, advocate for change, and take action on the causes of poor financial wellbeing.",,-99,University of Alberta,4395.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Policy research and interventions | Economic impacts,2023 +P26390,479539,Improving Awareness and Uptake of Systems-oriented Resources for Action on Poverty and Financial Wellbeing: An Integrated KT and Evaluation Project,"The COVID-19 pandemic increased financial strain and poverty, which has negative health impacts and widens health and social gaps. The worst impacts are felt among racialized peoples, women and younger people. Funded by CIHR, our international, multi-sectoral practice-research team developed a Public Health Framework and companion Guidebook. These evidence-based resources will help governments and organizations promote financial wellbeing at the population level. The Framework presents 17 areas for action. The Guidebook offers strategies and indicators to act on those areas. They are in PDF-document form, but knowledge users (KU) have strongly recommended an interactive website to better meet their needs. Our integrated knowledge translation (iKT) project aims to strengthen awareness and use of the Framework & Guidebook. We will work closely with KU to create a user-friendly website where users can seek guidance from the Framework & Guidebook tailored directly to their needs. Building on our work since 2018, we propose a participatory, multi-method project. We will: 1) work with KU to generate ideas and a website prototype; 2) refine and validate the website with a national end-user group, prioritizing equity-deserving groups; 3) co-develop end-of-grant KT strategies to share with diverse target audiences; 4) evaluate our process of working with KU and end-users to inform our work and add to the iKT literature; and 5) evaluate the project outcomes of reach, effectiveness, adoption, sustainability, and equity. Our project responds to a practice need and gaps in the academic literature. We will substantially improve awareness and uptake of these action-oriented resources among diverse end-users. This will improve their work on the design, delivery, and evaluation of programs and policies on poverty, financial strain and financial wellbeing. Our work will also address scholarly gaps on KT of systems-oriented frameworks that guide complex population-level initiatives.",,-99,University of Alberta,180015.03,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2023 +P26392,480802,Think Tank to support and strengthen workforce for eating disorders: A national planning event,"The COVID-19 crisis resulted in a startling increase in rates of eating disorders (EDs) among Canadian children and youth. The system was poorly equipped to respond to the increased needs. To better understand these needs and the gaps in our current ED system of care, a national team came together to look at prevalence and the social and economic impact of COVID-19 on EDs in children, youth, families and the system. This study sought to collect both national administrative data and data from ED community organizations. To further tell the story, the study also heard from approximately 125 individuals with lived experience, primary caregivers, clinicians and decision-makers via a survey and follow up discussion groups to hear their perspective. Next steps are to identify how to use this information to transform the health workforce to better the system of care for those with EDs. We will accomplish this by bringing together our already-collaborating partners to a 1-day event where we can generate a strategy for training larger workforce to address EDs. Invited partners are individuals and organizations with diverse expertise in the ED community, including individuals and families with living/lived experience and international collaborator Dr. Stephen Touyz representing the InsideOut Institute in Australia. The InsideOut Institute is a successful example of workforce building and system transformation in the field of EDs. The objectives of the current planning grant are to bring together diverse stakeholders to reflect on the costing data and learn from Australian colleagues to agree upon strategies for developing and providing training resources to healthcare professionals across Canada. The result of increasing the workforce would ultimately increase service delivery to those with EDs for the purpose of system transformation. Outcomes from the planning activity will be compiled into a report that provides guidance for the creation of this training platform.",,-99,Children's Hospital of Eastern Ontario Research Institute Inc,37519.86,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26396,462717,The Mental Wellness of Citizens of the Métis Nation: Before and during COVID-19,"The COVID-19 pandemic has been challenging and stressful for communities with ongoing changes, disruptions, and isolation. This has led to high levels of mental unwellness. Rates of anxiety and depression are on the rise across many groups. Yet little information is available on the mental wellness of Indigenous people related to the COVID-19 pandemic. Data that is available suggests continued disparity with poorer mental health in Indigenous compared to non-Indigenous populations. What remains unknown is Métis-specific mental health experiences. High-quality, timely data on the mental health outcomes of Métis people is crucial to inform the allocation of scarce mental health resources. Our rapid COVID-19 study will provide this information. As the only recognized Métis government in Ontario, the Métis Nation of Ontario is well positioned to lead this research to examine the mental wellness of MNO Citizens before, during and after the COVID-19 pandemic. Our study will use mixed methods to examine self-reported mental health through survey based data as well as health service administrative data and speaking directly with Métis Citizens to look at trends in mental wellness. Examining the experiences of mental wellness and unwellness among Métis Citizens during the pandemic is critical to informing the development of programs and strategies to improve outcomes post-pandemic and prepare for future pandemics or other public health emergencies. Results from our COVID-19 study can help inform decisions on resource allocation and prevention/intervention strategies to optimize Métis health.",,-99,Métis Nation of Ontario,196065.15,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26400,491199,"Emerging Infectious Diseases and Health Emergencies: Estimating the prevalence of the bacteria pneumonia and COVID-19 diseases, and quantifying COVID-19 impacts on vulnerable population such as opioid overdose for effective monitoring and planning.","My research aims to assist the Canadian government in combating emerging infectious diseases and protecting vulnerable populations. My research will focus on two infectious diseases, COVID-19 and bacterial pneumonia, and their impact on vulnerable populations, particularly those at risk of opioid overdose. My research will involve accurately enumerating the prevalence of infectious diseases, including undetected cases of COVID-19, and shifts in serotypes of Streptococcal pneumococcus. The impact of COVID-19 on vulnerable populations will be investigated, and a predictive model for opioid overdose will be developed based on observed patterns of change in opioid use and overdose. My research aims to contribute to the development of effective strategies to prevent and manage infectious diseases, leading to improved health outcomes for Canadians. Ultimately, my research will provide valuable insights into reducing the economic impact of COVID-19 in Canada by identifying services that may be at risk of virus transmissions as against total lockdown of services which has ripple effects on economy and leads to limited access to medical treatments of unrelated COVID-19 diseases.",,-99,University of Victoria (British Columbia),198239.44,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts | Economic impacts,2023 +P26405,484591,Using an agent-based model to simulate long-term mental health and labour market outcomes associated with Post-Covid Conditions among the Canadian working population.,"Most individuals who are infected with COVID-19 recover quickly, however for 1 in 6, symptoms including fatigue, shortness of breath and 'brain fog' can develop or persist for 3 months or longer after their initial infection. This condition is commonly referred to as long COVID and is estimated to have affected around 1.4 million Canadians. For those who experience long COVID, the effects can be debilitating, impacting ability to work, which can lead to long periods of absence, need for work accommodations or even job loss. Those with long COVID also commonly experience symptoms of poor mental health including anxiety and depression, which can be an additional cause or a consequence of inability to work. As a result, long COVID can have important social and economic impacts on the publicly-funded mental healthcare system and the Canadian workforce. This project aims to estimate the long-term impact of long COVID on employment and mental health outcomes to inform healthcare and economic policy and planning. Since the evidence on long COVID is rapidly emerging, the first step of this project is to collect and summarize evidence regarding the impact of long COVID on mental health and employment. The second step of this project is to use a simulation approach to predict the long-term impacts of long COVID on population-level mental health (eg cases of depression and anxiety, access to publicly funded mental health services, cost of mental healthcare), and employment (eg days of work lost and unemployment) outcomes 5 years from now. Finally, we will use this simulation technique to estimate the change in mental health and employment outcomes in the presence of specific interventions that are designed to promote recovery among those with long COVID. The findings of this project will help us to quantify the impact of long COVID and potentially identify effective interventions to lessen this impact, which will help inform healthcare and economic planning in Canada.",,-99,Public Health Agency of Canada,25737.44,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Indirect health impacts | Economic impacts,2023 +P26406,485108,Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 Pandemic and other extenuating circumstances: The CONSERVE 2021 Statement,"Rigorous design and transparent reporting of randomized trials and trial protocols are key enablers of open science. Trials can face unavoidable modifications due to new safety or efficacy information, regulatory revisions, changes in the standard of care, and more. Modifications can prompt methodological, ethical, feasibility, and analytical challenges that threaten open science. The COVID pandemic disrupted thousands of trials involving millions of participants. Scientists had no guidance on how to interpret and report those disruptions. CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve the reporting of trials and trial protocols that undergo important modifications in response to extenuating circumstances. CONSERVE was developed using open science principles, led by a global panel of 37 trial investigators, methodologists, patient representatives, ethicists, funders, regulators, and journal editors. Our protocol was published on the Open Science Framework, involving a literature review, consensus-based panelist meetings using a modified Delphi process, and a global survey of trial stakeholders. The literature review yielded 38 relevant documents, but no generalizable guidance for reporting unanticipated modifications to trials and protocols. The panel used these findings to develop a consensus guideline. The global survey drew 198 respondents in 34 countries, of whom 90% understood the concept definitions and 85.4% could use the implementation tool. Feedback from survey respondents was used to finalize the guideline. CONSERVE was immediately publicly available in June 2021 through JAMA and the EQUATOR Network. CONSERVE offers tools and checklists to support transparent and rigorous reporting when trials and trial protocols face important modifications to the intended study. The panel is investigating the impacts of the CONSERVE 2021 Statement and the quality of trial reporting during the COVID pandemic.",,-99,University of Toronto,18759.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures",,2023 +P26407,485089,Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 Pandemic and other extenuating circumstances: The CONSERVE 2021 Statement,"Rigorous design and transparent reporting of randomized trials and trial protocols are key enablers of open science. Trials can face unavoidable modifications due to new safety or efficacy information, regulatory revisions, changes in the standard of care, and more. Modifications can prompt methodological, ethical, feasibility, and analytical challenges that threaten open science. The COVID pandemic disrupted thousands of trials involving millions of participants. Scientists had no guidance on how to interpret and report those disruptions. CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve the reporting of trials and trial protocols that undergo important modifications in response to extenuating circumstances. CONSERVE was developed using open science principles, led by a global panel of 37 trial investigators, methodologists, patient representatives, ethicists, funders, regulators, and journal editors. Our protocol was published on the Open Science Framework, involving a literature review, consensus-based panelist meetings using a modified Delphi process, and a global survey of trial stakeholders. The literature review yielded 38 relevant documents, but no generalizable guidance for reporting unanticipated modifications to trials and protocols. The panel used these findings to develop a consensus guideline. The global survey drew 198 respondents in 34 countries, of whom 90% understood the concept definitions and 85.4% could use the implementation tool. Feedback from survey respondents was used to finalize the guideline. CONSERVE was immediately publicly available in June 2021 through JAMA and the EQUATOR Network. CONSERVE offers tools and checklists to support transparent and rigorous reporting when trials and trial protocols face important modifications to the intended study. The panel is investigating the impacts of the CONSERVE 2021 Statement and the quality of trial reporting during the COVID pandemic.",,-99,University of Toronto,18759.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26410,459197,Noochokooyishi Anavaan (The Ways Forward): An equity-focused approach on the impact of the COVID-19 pandemic and perspectives on future pandemic responses among Métis in Alberta,"The COVID-19 pandemic has affected people around the world. Yet, the problems of the COVID-19 pandemic are not equal for all. The pandemic has affected Indigenous peoples and increased their risk for poor health. Colonialism has played an important role on COVID-19 consequences among Indigenous people. In particular, we do not know much about Métis experiences during the covid-19 pandemic. The Métis Nation of Alberta (MNA) in collaboration with academic allies conducted the first study in Canada (Misi Yehewin (""big breath"" in Michif) to evaluate physical, mental health and well-being among ~1,500 Métis Albertans aged 16 years and older at different stages of the COVID-19 pandemic. The proposed study, Noochokooyishi Anavaan (""the ways forward"" in Michif), aims to explore risk and resilience factors associated with Métis health, well-being, and health care use during the pandemic and before and after COVID-19 vaccination. The study will also hold community gatherings to understand the experiences of Métis Albertans during the pandemic and will reach consensus among Métis knowledge holders responsible for decisions related to the MNA's responses to pandemics that are responsive to the lived realities of Métis people in Alberta and supportive of Métis' self-determination. This research will inform the design and adoption of culturally appropriate pandemic response plans that consider Métis health and well-being needs.",,-99,University of Alberta,192415.45,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Community engagement,2021 +P26412,444982,Role of Angiotensin Converting Enzyme 2 in Cardiovascular Complications due to Metabolic Disorders,"Diabetes mellitus (DM) and obesity is the fifth leading cause of death worldwide and a major risk factor for various heart, vascular, and kidney diseases. Inhibition of the renin-angiotensin system (RAS) using angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) are key therapies for patients with diabetes. The ACE2/Ang 1-7 pathway provides a novel axis in the RAS which can be enhanced to provide therapeutic effects. The therapeutic relevance of our strategy is strengthened by the current clinical trials using rhACE2. ACE2 is also the receptor for the SARS-CoV-2 and our findings will have implications for patients with COVID-19. Relevance and Significance: We are studying strategies of enhancing Ang 1-7 action and/or ACE2 effects in male and female type 2 diabetic model with advanced diabetic complications and in diet-induced obese models. Despite the use of ACE inhibitors and angiotensin receptor blockers, diabetic cardiovascular complications remains major global health burdens for our patients and new therapies are needed. Our potential new therapies could have a dramatic beneficial impact on diabetic and obesity mediated micro and macrovascular complications. Importantly, we will also determine the sex-specific differences in these models and the response to increasing ACE2.",,-99,University of Alberta,662447.81,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2021 +P26413,471045,Tracking the Role of Income Inequality on the Widening of Health Inequities During the COVID-19 Pandemic Among Adolescents Participating in the COMPASS Cohort Study,"Before the COVID-19 pandemic, adolescents living in areas with high income inequality, or areas with large gaps between rich and poor, were more likely to have higher depressive and anxiety symptoms, more likely to use marijuana and e-cigarettes, and binge drink, in comparison to those living in areas with low income inequality. During the COVID-19 pandemic, the adverse association between social inequities and health outcomes may have worsened. The pandemic and public health measures disproportionately impacted people across socioeconomic status, racial/ethnic, immigrant, and gender groups. In this proposed investigation, we will study the association between income inequality and adolescent health outcomes, such as depression and anxiety, and substance use, such as cannabis use, cigarette smoking, and alcohol use throughout the pandemic. We hypothesize that health disparities observed before the pandemic will widen from 2019-2022. We will also test whether associations differ across socio-demographic groups. Finally, we will study potential mechanisms involved in which income inequality leads to health outcomes among adolescents.",,-99,University of Alberta,54827.59,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26415,459202,Artificial intelligence-based analysis of cough for COVID-19 screening in Montreal,"Cough is a key symptom of respiratory diseases, including COVID-19. The ongoing COVID-19 pandemic has accelerated advancements in the field of digital cough monitoring using artificial intelligence (AI). Prior studies and AI models have shown that AI can identify human coughs from ambient sounds (cough detection) and can potentially differentiate coughs caused by different diseases (cough classification). For example, there is a promising smartphone application named Hyfe Research that uses AI to detect human cough, with more than 97% accuracy. Such AI models can be used on smartphones, allowing for non-invasive, easy to use tools. In this study, we will develop and evaluate a cough classification AI model which can be used on smartphones to differentiate COVID-19 coughs from coughs caused by other diseases (e.g., influenza). In a case-control study design, coughing patients with confirmed COVID-19 infection and negative controls will be recruited at the Centre Hospitalier de l'Université de Montréal (CHUM) in Montreal, Canada (close to 500 participants in total). Clinical and demographic information will be collected, and ten coughs will be recorded using the Hyfe Research app. Using these cough sounds, we will train algorithms to differentially identify COVID-19 coughs from non-COVID-19 coughs and compare how well the algorithm performs against the laboratory reference standard. We will also conduct in-depth interviews with patients and healthcare providers to understand the feasibility and acceptability of smartphone-based cough recording in a clinical setting. This study will contribute to a global database of COVID-19 cough sounds. The development of a reliable AI application for cough detection could improve COVID-19 screening strategies, and thus mitigate future infections and outbreaks in Canada, and around the world.",,-99,Centre hospitalier de l'Université de Montréal (CHUM),354806.2,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P26418,454865,Canada's COVID-19 Vaccine Confidence in Indigenous Populations: A Mixed Method Study,"Vaccines are important public health invention to curb many lethal diseases like smallpox. Vaccines are not always accepted by the people and there is a lot of hesitancy. People are misinformed on vaccine related research and hence reluctant to receive vaccines. Such vaccine hesitancy is found to be more common in the Canadian Indigenous populations than in the non-Indigenous populations. Thus, we are proposing an in-depth learning of the reasons of vaccine hesitancy in the First Nations (FN), Metis, and Inuit people. We are building this project on the ongoing CIHR-funded COVID Impact project at the Bridge Engagement Center, a community-based research center in Ottawa, Canada. Thus far, the COVID Impact project has successfully recruited 397 participants, collected detailed data around all objectives via a survey administered by peers with lived experience. A preliminary analysis of the COVID Impact project (N=397; Indigenous=138 (FN=46, Inuit=61, Metis=9, Mixed=10 and Did not mention any specific tribe=12)) demonstrated significantly more vaccine hesitancy in the FN and Inuit participants. The proposed study will follow a community based participatory action research approach, designed, and operationalized in previous Bridge studies. We will conduct 3 peer-led Focus Groups (1 each with FN, Metis, and Inuit) and 25-30 semi-structured interviews to learn vaccine hesitancy in the Indigenous populations. The short-term outcome of the study will benefit Indigenous populations, as their unique needs and challenges will be identified to inform Ottawa specific COVID-19 vaccine insecurities and strategies for implementing public health responses to strengthen vaccine confidence. We will co-create Grade-6 reading level material around vaccine hesitancy, barriers, and facilitators of vaccine confidence, specific for Indigenous populations. In the long-term, findings from this project will help guide vaccine strategies for Indigenous communities with a people first approach.",,-99,Ottawa Hospital Research Institute,6632.03,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P26419,449179,Evaluating the impact of pharmaceutical interventions to reduce overdose among people with criminal justice system involvement in British Columbia,"People who have been incarcerated (i.e. in prison) are more likely to use illicit substances (e.g. heroin, methamphetamine) compared to the general population and are at higher risk of negative outcomes including overdose and more rapid and/or frequent return to prison. Efforts to address overdose, both in prisons and in the community, have been focused on treatment for people with opioid addiction, by prescribing medications that have been shown to help people to stop their illicit opioid use. This alone may not be sufficient to reduce illicit opioid use, particularly among people who also use other substances. In March 2020, in the context of COVID-19, British Columbia's Ministry of Health took a significant step to expand access to prescription medications for people with substance use disorders (i.e. drug addictions), by providing doctors with new guidelines and permissions for prescribing opioids, stimulants, benzodiazepines, and alcohol withdrawal management medications to people at risk of overdose. The goal of this study is to investigate whether these guidelines have been effective at reducing overdose and criminal justice system involvement. Provincial health and criminal justice system records will be examined to identify how many people with and without criminal justice system involvement have substance use disorder diagnoses (and which type of diagnosis) in British Columbia. Trends of overdose and criminal justice system involvement will be examined to identify changes since prescription medication programs were expanded. Findings will highlight gaps in substance use services in British Columbia, and will inform policies and programs that can reduce overdose in both criminal justice and community health systems.",,-99,B.C. Centre for Disease Control (Vancouver),85055.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2021 +P26420,485627,Sexual Health and Wellbeing of Sexual Minority Men: Insights from the Engage Cohort Study,"Gay, bisexual, and other men who have sex with men (GBM) are disproportionately represented in new cases of HIV and other sexually transmitted bloodborne infections (STBBI). The Café Scientifique will discuss research from the CIHR-funded Engage Cohort Study covering several themes including: (i) rates of HIV and STBBI among GBM in Toronto and other large metropolitan centres in Canada; (ii) the efficacy and uptake of various HIV and STBBI interventions, and (iii) how sexual risk taking behavior changed through the COVID-19 pandemic. The researchers will discuss these findings in light of increasing uptake of preventative HIV medication (i.e., pre-exposure prophylaxis) and shifts in HIV treatment attitudes, and how this may affect GBM sexual behavior. The venue will be the 519 Church Community Centre, which is the community centre for LGBT communities and others in the downtown area. The 519 Community Centre is an ideal setting for a community event where researchers and community members can chat, as it is a gay-friendly space, easily accessible via public transport, and disability-accessible. Our Café will be accessible to the public, stimulating discussion between public participants and experts. We will broaden the reach of our Café by web casting the event and inviting knowledge-users from ASOs and other groups who cannot physically attend to gather participants and join in on the conversation. All Café attendees will receive the CIHR Café Scientifique Evaluation Survey, which will include supplementary questions that evaluate if the Café was informative to the participant, and if it met its stated objectives. The speakers and facilitators will also independently evaluate the event and provide a final report summarizing event activities.",,-99,Toronto Metropolitan University,4412.13,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26424,466907,Development of an in vitro pseudo-neutralization assay to evaluate the efficacy of anti-SARS-CoV-2 antibodies,"Coronavirus disease (COVID-19) is a viral disease that emerged in 2019 and was declared a global pandemic in March 2020. Since then, the virus has killed millions of people and had disastrous socioeconomic impacts around the world. A better understanding of immunity to the virus that causes COVID-19 is essential for the development of vaccines and treatments. Given the recent emergence of this virus, the immune mechanisms specific to it are not yet well understood. However, we do know that infected people develop antibodies that protect them from reinfection. These antibodies are proteins produced by the body that bind to proteins on the virus to prevent it from entering cells. We have previously studied the amount of antibodies in infected people for 24 weeks after being diagnosed with COVID-19. This next project will follow up by studying the effectiveness of these antibodies in neutralizing the virus. We will develop an experiment that can measure it to determine whether it is related to the severity of symptoms in infected people. In addition, these experiments can help us better understand the links between different aspects of immunity, such as the level, type and duration of these antibodies, as well as other clinical parameters.",,-99,Université de Montréal,13724.56,Human Populations | Viruses | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Immunity | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +P26425,486176,Improving Community Mental Health Services for Women and Children Impacted by Violence,"Gender-based violence (GBV) is a public health crisis in Canada. Exposure to GBV has been linked to mental health problems including high rates of depression and substance use in women and more social-emotional challenges in children. An effective method to lessen these negative outcomes is through accessible mental health services offered through community-based organizations (CBOs). However, COVID-19 has severely shifted service delivery methods and funding structures for CBOs, increased client needs, and exacerbated service provider stress. Given this disruption, a gap has emerged in the research for CBOs on how to best support families and children experiencing GBV. Intake processes (IPs) that include an evaluation of client needs at the start of service appears to be a pathway for CBOs to improve organization functioning and support both staff and clients. However, there is limited research on how to best create and implement IPs to meet the increasingly complex needs of families following COVID-19. Thus, the proposed study will use research-backed strategies to aid CBO stakeholders to create and implement an IP designed to better support women and children. Specifically, this study will explore if updated IPs in CBOs is an appropriate way to improve service delivery, such that the mental health and distress of women and children in the context of GBV is reduced. I hypothesize that an IP that addresses current organization, staff, and client functioning will result in improved service as indicated by staff-reported themes and ratings of approval. Outcomes of this study may improve CBO staff satisfaction and commitment to service delivery and provide a model for CBOs so that organizations can leverage IPs to support women and children in the context of GBV.",,-99,University of Toronto,13021.09,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P26426,456341,Real-time Infection Control and Antimicrobial Stewardship Through Wastewater-Based Surveillance,"Wastewater (WW)-based epidemiology is an emerging science that seeks to understand the health of a population through sewage analysis. Our group proposes to focus this technology on hospitals. Hospitals are where those most susceptible to infections and their consequences are cared for. Accordingly, new methods to determine the day-to-day health of hospital populations are of extreme importance, and hospitals' sewer pipes contain invaluable information. WW will be collected from a range of points in hospitals in order to capture entire facilities and units of specific interest (i.e. intensive care). Samples will be concentrated and purified to enable molecular diagnostic testing for; 1. Viral Outbreaks. Hospital-associated outbreaks of viruses such as SARS-CoV-2, influenza and norovirus can easily occur when unrecognized cases enter from the community. We will identify and quantify target-viruses in WW and compare these with clinically identified cases and outbreaks in patients and healthcare workers in order to develop predictive modelling tools to establish a WW ""early-warning"" system. 2. Antimicrobial resistant organisms (ARO). ARO are prevalent in hospitals as a consequence of pervasive antibiotic use. ARO colonized individuals are at increased risk of harm and death. Current ARO monitoring strategies focus on only active infections, and rare surveillance screens - and as such miss most cases. By tracking and comparing ARO in WW with hospital-wide infection and antibiotic usage data we will develop real-time actionable tools that provide a day-to-day ""snap-shot"" of AROs in hospital - informing practice - and saving lives. Our transdisciplinary team, comprised of individuals with diverse backgrounds in engineering, chemistry, infectious diseases and microbiology, have the experience, track-record and tenacity to develop and implement a pilot hospital-WW infection surveillance system providing meaningful and actionable data to inform patient care.",,-99,University of Calgary,78858.79,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2021 +P26429,456744,The Mental Health and Wellbeing of Unpaid Caregivers: An Intersectionality-Informed Mixed Methods Study,"About 28% of Canadians are in unpaid caregiving roles and they are the backbone of the Canadian healthcare system. Unpaid caregivers provide 75% of care services at home. Unpaid caregiving can impact one's physical and mental wellbeing, finances, and ability to work outside the home and be paid. We received funding from CIHR for a rapid integrated mixed methods systematic review of the existing literature to determine the mental health status of unpaid caregivers during COVID-19 (Phase 1). Our results suggest unpaid caregivers are young, White, highly educated, married and female. They are stressed, anxious and depressed. However, these results really do not give us a clear picture of unpaid caregivers in Canada because 1 in 5 people in Canada is born elsewhere; the three largest racial and ethnic minority groups are South Asians, Chinese and Blacks - accounting for about 60% of the Canadian racial and ethnic populations. We also do not know about the mental health of unpaid caregivers who might be men, unmarried and less educated. By 2035, the annual unpaid caregiver contribution to the Canadian healthcare system is estimated to be $128 billion. We need to find out about the wellbeing of unpaid caregivers at the different intersections of race and ethnicity, age, sex and gender. We will continue to work with patient partners (i.e., unpaid caregivers) as investigators on our team to complete Phases 2 and 3 of our study. We will distribute a survey in Phase 2a, then invite a sub-group of unpaid caregivers with fair/poor and good/excellent wellbeing to an interview (Phase 2b). In the interview we will explore how race and ethnicity, sex, age, and gender intersect to affect unpaid caregiver's wellbeing. We will then have a virtual consensus meeting with unpaid caregivers and decision-makers to discuss what policies/guidelines and interventions need to be developed to improve unpaid caregiver's wellbeing. We are focusing on equity, diversity and inclusion.",,-99,University of Toronto,78858.79,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26430,468879,Partnering with Canadian Youth and Families to Co-design a User-centered Digital Health Tool to Manage the Effects of the COVID-19 Pandemic and Future Public Health Crises on Youth Mental Wellbeing,"On March 11, 2020 the World Health Organization declared the novel coronavirus COVID-19 disease a global pandemic. The Canadian government implemented physical distancing measures and widespread closure of public institutions. This resulted in social isolation, reduced access to support within schools and community settings, as well as fewer opportunities to engage in protective activities such as physical activity. These impacts are likely to have detrimental short- and long-term effects on youth mental wellbeing. Care for youth with mental health disorders was already overstretched and underfunded before the pandemic. Thus, there is a pressing need to partner with youth and families to target and improve youth mental wellbeing prior to the onset of a mental health disorder, as well as to conduct research on youth mental wellbeing needs related to pandemic recovery. Our team will address this gap through a national research study that will result in the development of a catalogue of recommendations specific to supporting youth mental wellbeing, and a digital tool to support youth mental wellbeing. This will be achieved in three phases of work: 1) expert consultation on data related to supporting youth mental wellbeing existing within our Pandemic Preparedness research program; 2) development of an innovative digital tool for youth mental wellbeing; and 3) assessment of the tool's usability and acceptability. This study will complement ongoing parallel research in youth currently being conducted by our team that involves partnering with Canadian youth and families to understand the unique implications of the pandemic on this vulnerable population. The ultimate goal of the proposed work is to build on this foundation by cataloguing recommendations specific to supporting youth mental wellbeing and developing a digital health tool in partnership with youth and families to support pandemic recovery and resilience in the face of emerging public health crises.",,-99,Dalhousie University (Nova Scotia),78037.89,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26432,448892,Évaluation de l'efficacité des probiotiques sur les affections post-COVID-19.,"La pandémie COVID-19 a touché plus de 138 millions de personnes et si la vaccination apporte un espoir important, de nombreuses questions demeurent (ex : impact des variants du virus). Des études démontrent que des patients pourraient présenter des symptômes jusqu'à 6 mois après la phase aigüe (fatigue, anxiété...). Les causes du COVID de longue durée (LONG-COV) sont peu connues mais pourraient être liées à une persistance du virus ou une réponse immunitaire inadéquate. Notre groupe propose d'étudier l'impact du microbiote intestinal (flore intestinale) sur le LONG-COV. Nous savons que : 1) les personnes qui présentent une forme grave de la COVID-19 (personnes âgées, diabétiques...) ont souvent un déséquilibre du microbiote intestinal, 2) la COVID-19 modifie le microbiote (ex : prise d'antibiotiques) et 3) les probiotiques peuvent améliorer l'équilibre du microbiote. Nous émettons l'hypothèse que la LONG-COV est associée aux conséquences du déséquilibre du microbiote intestinal et qu'il est possible de réduire la survenue de la LONG-COV à l'aide de probiotiques. Comme le microbiote intestinal est en étroite relation avec les poumons et le cerveau, l'action des probiotiques pourrait aussi atteindre les autres organes touchés par la LONG-COV. Nous proposons une étude qui compare la prise de probiotiques à celle d'un placébo. Nous inclurons 618 hommes et femmes âgés de 18 ans et plus, symptomatiques de la COVID-19 avec un test COVID + depuis 10 jours ou moins. Les patients hospitalisés (population à risque de LONG-COV) peuvent être inclus s'ils sont revenus à leur domicile en moins de 10 jours après le diagnostic. Les signes de la LONG-COV seront étudiés au 30e et au 90e jour (internet ou téléphone). Un groupe de patients volontaires effectuera des prélèvements (salive et selles) pour les analyses de virus et du microbiote. En cas de succès, les probiotiques pourraient être utilisés très rapidement dans tout le Canada (peu d'effets secondaires, coûts abordables).",,-99,Université de Sherbrooke,792278.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Post acute and long term health consequences | Clinical trials for disease management",2021 +P26433,459287,Modulation of immune responses to COVID-19 vaccination by intervention on the gut microbiota: a randomized controlled trial.,"Older people, who often have more fragile health, have been particularly affected by the COVID-19 pandemic. The results of recent studies show that, while vaccines have shown very good short-term efficacy, the protection of older people may be insufficient, 6 months after the 2nd dose. Some countries have started to offer a 3rd dose. We are considering acting on the intestinal flora of older people (which is often unbalanced) in order to increase the effectiveness of vaccination. Indeed, it has been shown that probiotics (which can rebalance the intestinal flora) significantly increase the production of antibodies after vaccination against the influenza virus. Our hypothesis is that taking probiotics one month before and one month after the 3rd dose of COVID vaccine would provide longer-lasting vaccine protection in older people. Our study will include 668 seniors, aged 65 to 89, who have not had COVID-19, who have received 2 doses of the same vaccine and who will accept a 3rd dose of vaccine. All participants will take one capsule/day (probiotics or placebo) for 2 months and, in the middle of this period, they will receive a 3rd dose of vaccine. Participants will have to travel 3 times to the Sherbrooke Clinical Research Center (inclusion visit, vaccination and final visit). On five occasions (inclusion, vaccination 1 month, 3 months and 6 months post-vaccination), they will prick their fingertip and express the drop of blood on blotting paper. They will mail this dried blood sample in an envelope so that the antibodies can be measured in Quebec City. We expect to reduce by 1/3 the number of seniors poorly protected by the 3rd dose of vaccine 6 months after the injection thanks to probiotics. If successful, this approach could quickly be implemented worldwide because probiotics have few side effects and are affordable.",,-99,Centre de Recherche clinique Etienne-Le Bel/CHUS,788438.07,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2021 +P26435,475880,Identifying Key Long-COVID Biomarkers with Machine Learning Analysis,"According to the CDC, 1-in-5 adult COVID-19 survivors suffer from widespread symptoms referred to as ""Long-COVID"". Long-COVID symptoms vary greatly between patients which results in increased disease complexity and diagnostic/therapeutic challenges. This project aims to identify the key Long-COVID biomarkers to improve clinical practice while also increasing our understanding of the disease. Although several general mechanisms have been proposed to explain the symptoms, they are limited by a lack of Long-COVID specific biomarkers and pathophysiological mechanisms. The varying symptoms make it challenging and inefficient to conduct research that targets specific physiological regions or mechanisms. As blood flows throughout the body, measuring blood biomarkers enables the investigation of multiple system changes and interactions that contribute to Long-COVID. A total of 2943 blood biomarkers will be measured for healthy controls, COVID-19 Ward inpatients, COVID-19 ICU inpatients and Long-COVID outpatients. I will analyze the large dataset with machine learning algorithms (AI) to identify the most important biomarkers that differentiate Long-COVID subjects from the other groups. Moreover, I will identify where these biomarkers are expressed to determine key organ systems and cell types affected by Long-COVID. Expression analysis in this manner will be a novel application of AI and will advance the field of blood biomarker analysis. As there is currently no test for Long-COVID, the identified biomarker model can serve as a diagnostic test. Individuals affected by COVID-19 can be proactively screened for their risk of Long-COVID and receive preventative measures. The blood biomarkers also enable targeted treatments and new streams of inquiry that investigate the identified biomarkers. The biomarker model developed will impact the decision-making of physicians and result in better patient outcomes.",,-99,"Schulich School of Medicine and Dentistry (London, Ontario)",77083.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P26440,498296,Dapagliflozin for Long COVID Syndrome,"An estimated 30 million Canadians have been infected by the virus causing COVID-19 since the start of the pandemic. A recent Canadian survey found that 10-30% of COVID survivors describe long-term symptoms, with daily activities often limited by fatigue and shortness of breath. This condition is referred to as long COVID syndrome. Other studies have also shown that patients have a 50-70% higher risk for diabetes and heart disease in the first 12 months following COVID-19 infection. We recently evaluated 215 patients at 3-6 months post-COVID-19 infection and compared them to 133 patients without prior COVID-19. We performed whole body MRI and found significant abdominal fat accumulation in patients with prior COVID-19. Abdominal fat has been linked to a number of health issues including an increased risk for diabetes and heart disease. We also found that fat accumulation in the leg muscles was associated with long COVID symptom severity. We are the first group to identify these abnormalities in patients with prior COVID-19 infection. Dapagliflozin is a drug therapy that reduces the risk of heart disease in patients with diabetes and it has also been shown to reduce fat volumes in the abdomen. This medication has been studied in patients with acute COVID and was shown to be safe. However, dapagliflozin has not been evaluated in patients with long COVID syndrome. For this study, we will recruit 706 patients with long COVID syndrome and randomly assign them to 12 months of dapagliflozin or a placebo pill. All patients will undergo MRI to assess fat content in their abdomen and leg muscles. We expect to find that patients taking dapagliflozin will have lower abdominal fat and a lower risk for developing diabetes and heart disease. If dapagliflozin is found to be effective then it would be the first proven treatment of long COVID syndrome. It could immediately be used to help patients with this poorly understood condition.",,-99,University of Ottawa Heart Institute,74067.61,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Post acute and long term health consequences | Clinical trials for disease management | Prophylactic use of treatments,2023 +P26441,473339,The Cognitive Profile of COVID-19: Longitudinal Neuropsychological Outcomes Following Infection,"Evidence suggests the virus causing COVID-19 invades the brain, raising concern over the potential for long-term impacts on thinking abilities and everyday functioning. Our current CIHR funded study is characterizing cognitive functioning in COVID-19 positive individuals following physical recovery, and we now aim to track cognitive changes over time and identify risk factors for poorer long-term cognitive outcomes. Adults who tested positive for COVID-19 and acutely recovered, and those with no evidence of infection, are completing a series of cognitive and psychological tests via reliable, and valid videoconferencing techniques in our current study. The proposed study will follow these individuals over time, with 2-year follow-up assessments to examine changes in cognition. We are comparing test performance to determine group differences in cognitive functioning, mental health, and other factors at baseline, will re-assess group differences after 2 years, and will test a screening measure to detect these cognitive difficulties. Our follow-up study will examine the extent to which medical and mental health factors (e.g., other pre-existing medical conditions, vaccination status) may interact to play a role in cognitive changes, and how well a screening measure is able to detect COVID-related cognitive difficulties. Findings will inform clinicians (e.g., neurologists, neuropsychologists, rehabilitation specialists), on expectations for trajectory of potential recovery of function, and on how to optimally develop and deploy services in Ontario, BC, and other jurisdictions in Canada, with relevance to international health care communities. Results will help to ensure secondary impacts of COVID-19 infection are appropriately addressed, so that those affected by this virus are able to most efficiently resume complex daily activities requiring cognitive effort, including employment and academic pursuits.",,-99,University of Victoria (British Columbia),76662.06,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Indirect health impacts,2022 +P26442,459195,COVID-19 and Indigenous public health sovereignty in British Columbia: Addressing systemic inequity through community-driven solutions,"Indigenous peoples in the Western hemisphere have a tragic history with communicable disease. In the aftermath of contact, smallpox devastated Indigenous peoples. This project examines Indigenous community-driven solutions to COVID-19. Narratives of disease among First Nations are often deficit-based, aligning with patterns of systemic racism. This work challenges racist narratives, through an examination of community-driven health sovereignty-based solutions, to COVID-19. In British Columbia (BC) government responses to COVID recognized Indigenous peoples are vulnerable due to several factors: lack of access to healthcare, socioeconomics, and numerous comorbidities. Factors dovetail with vulnerabilities experienced in the aftermath of major climate events including wildfires. In BC, First Nations have begun to take greater control over their health care services. Though the pandemic exacerbated challenges, this research examines how health sovereignty was maintained and amplified amid the crisis. Such evidence is crucial to how First Nations successfully managed COVID-19. Of significance is how First Nations struggled to assert jurisdictional authority and maintain territorial integrity in protecting community. As communities went through restrictions, examples emerged where First Nations reinforced nation-based territorial boundaries to promote health sovereignty. This project explores Indigenous health protocols used to create health security, and measures success in amplifying health sovereignty. This work uses a mixed methods approach to examine territorial health sovereignty, drawing on OCAP® principles, interviews and community-based research methods. The main objective of this research is to produce and mobilize knowledge - applying the learnings from successful First Nations COVID-19 responses to mitigate the spread of COVID-19 and improve detection and management for self-determined First Nation communities and populations.",,-99,"Simon Fraser University (Burnaby, B.C.)",158348.45,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement,2021 +P26443,450598,Changes in Health behaviours among Adolescents and Social-Ecological influences: Pandemic Evidence for an Equitable Recovery (The CHASE PEER Study),"The COVID-19 pandemic and related mitigation measures have affected the health and lifestyles of youth across the world. Changes such as school closures to in-person learning, diminished extracurricular activities, reduced wages, and divestment in non-pandemic-related public health measures have greatly affected the physical activity, sleep, screen time, substance use, and eating habits of youth. These health behaviours are especially important in adolescents because the habits they develop now, carry over into adulthood, and increase risk for future chronic diseases. Adopting and maintaining healthy habits in adolescents, and preventing or delaying the onset of risk behaviours, can impact health across the lifespan, thus reducing the social and economic burden of disease for all Canadians. The negative effects of the pandemic are likely to be even greater for youth already experiencing health inequalities related to gender, race/ethnicity, and family income. Social relationships, neighbourhood resources (such as parks, community centres, and other facilities and programs), and school-based programs and policies may help reduce this impact. Identifying who is most affected and what factors can minimize the negative effects of the pandemic will help Canada target resources towards adolescents and communities that need them most and ensure that any changes are effective. We will use Canadian data collected by our team before and throughout the pandemic, to address questions about 1) what groups of adolescents were most negatively affected by the pandemic, and 2) what supports reduced this risk? Funds will be used to ensure that we have the resources and person-power to prioritize this important work, and then communicate it effectively to promote an equitable recovery. We will engage youth, public health organizations, and schools as partners to ensure our research reflects the diverse experiences of adolescents and meets the needs of those who can create change.",,-99,Brock University (Ontario),63580.28,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26451,467034,Impacts of the COVID-19 pandemic on sexual and reproductive health services and well-being amongst urban Indigenous women - Implications for Indigenous well-being and reproductive justice,"There is a need to understand how the COVID-19 pandemic has impacted social and structural health inequities for Indigenous women and gender diverse peoples (2S/LGBTQ+). Ongoing colonial violence and gender-based violence continues to impact the health of marginalized populations, including Indigenous peoples, 2S/LGBTQ+, and sex workers. Historical and ongoing colonial violence has impacted Indigenous sexual and reproductive health (SRH) and Indigenous women face multiple barriers to accessing reliable contraception pre-pandemic. This research will examine how the COVID-19 pandemic has impacted access to SRH services and changes in self-reported mental health and well-being amongst Indigenous women (cis and trans) and Two-Spirit peoples, with a focus on structural and social determinants of these outcomes. Nested within a program of Indigenous health equity research and using Indigenous methodologies, this research will involve working with a nested community-based cohort of Indigenous women (cis and trans) and Two-Spirit people (N=300) in Vancouver housed at the Centre for Gender and Sexual Health Equity. Guided by the Indigenous Matriarch Board, this research will amplify Indigenous voices and inform actions to support culturally safe SRH health, social well-being, and justice for Indigenous peoples. Utilizing the CGSHE's cutting edge KTE resources, I will actively disseminate my findings and make my findings accessible to local and regional Indigenous populations, community organizations, knowledge-users, and researchers.",,-99,"Simon Fraser University (Burnaby, B.C.)",13724.56,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People | Sexual and gender minorities | Sex workers,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26452,494296,How Social Isolation Alters the Brain and Behaviour,"Over the last 10-20 years, concerns have been growing about how social isolation and loneliness affect people's mental and physical health, particularly among the elderly who are especially vulnerable to isolation. These problems were also exacerbated by the recent COVID-19 pandemic, which resulted in the unintentional consequence of increasing loneliness and isolation. People experiencing social isolation have increased rates of physical and mental health problems, such as cardiovascular disease, depression, anxiety, have a decreased quality of life, and an increased likelihood of death due to any cause. Interestingly, social isolation in both people and in animals cause similar behavioural changes such as reduced sleep, inactivity, and memory problems. Even though social isolation and feelings of loneliness are linked to such negative health outcomes, very little is known about how a lack of social experience changes the brain to cause behavioural and physical changes. Here, we will study the behavioural changes caused by isolation. Using the model organism Drosophila melanogaster, we recently discovered that social isolation reduces the numbers of synapses in their brains by 20-40%, and we find Drosophila exhibit behavioural changes including decreased sleep, reduced activity, and impaired memory, similar to what is seen in people. Through the experiments proposed, we aim to determine how a lack of social experience causes this reduction in synapses, and how it alters information processing in the brain, leading to the behavioural changes we see. Understanding the neurobiological underpinnings of how social interaction alters the nervous system can reveal fundamental properties about our nervous systems and methods to mitigate or reverse the detrimental effects of social isolation in people.",,-99,University of Alberta,73558.84,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P26456,422617,Determination by simulation of the typical profile and values ​​of healthcare professionals who will decide to get involved in or withdraw from the care of patients with COVID-19.,"The SARS-CoV-2 virus is receiving widespread media coverage due to the deaths attributable to it. Health centres in Canada are monitoring its development and are attentive to the appearance of any new cases. This viral disease can be frightening and health professionals may fear for their safety or that of others when intervening with infected people. This choice to intervene or withdraw from care is generally easy to make in the absence of a real threat and is subject to a rational and conscious process. However, when a person is subjected to a real and imminent threat, they feel stress and fear. This fear, rational or irrational, plays an important role in the decision to intervene or flee. Currently, we do not know how health professionals react when faced with an imminent threat such as SARS-CoV-2. We do not know the profile of people who would agree to intervene, nor that of people who would prefer not to. In this study, we want to create an authentic simulation environment reproducing an epidemic situation. Randomly selected participants (nurses, doctors and attendants) in five Canadian healthcare institutions will be called upon to intervene with people infected with the coronavirus. Through this in situ simulation, we seek to reproduce the mental state in which the healthcare professional will find themselves when intervening with this population. We will thus be able to determine the profile of people ready to intervene, using qualitative and quantitative analysis. Hospitals will be able to use the results to determine the people likely to intervene effectively and efficiently in the event of a major outbreak in order to reduce the organizational and human risks of the epidemic.",,-99,Université Laval,163611.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2020 +P26457,468876,ARtificial intelligence to Enable Automated REspiratory illness Surveillance through Primary care (AREA-RESP),"COVID-19 has demonstrated the urgent need to detect and monitor emergent respiratory illnesses of epidemic or pandemic potential. In part 1, we will develop and evaluate algorithms that process primary care electronic medical record (EMR) data for case detection of acute respiratory illness. We will take advantage of a unique dataset to train models employing artificial intelligence (AI), where clinicians have diagnosed (or not) respiratory illness in 11,287 encounters, as part of the Public Health Agency of Canada (PHAC) FluWatch program. In part 2, we will go on to evaluate implementation of the most accurate approach for automated respiratory surveillance in practices that are part of a network of all seven practice-based research networks in Ontario (>1.5 million patients). Our study team includes experts in primary care, respirology, infectious diseases, EMR data, public health, epidemiology and computer science. Working with knowledge users, AREA-RESP will provide a foundation for national, representative population-based, real-time surveillance systems to monitor respiratory illness. Our work directly aligns with the Chief Public Health Officer priorities for public health system transformation to improve pandemic readiness, to leverage foresight tools, and to leverage big data and technology.",,-99,Unity Health Toronto,78388.39,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2022 +P26458,460447,Public health and healthcare system collaboration to achieve the Quadruple Aim and build Learning Health Systems,"While the Quadruple Aim consists of goals for healthcare systems, public health shares the goal of improving the health of populations. As we emerge from the COVID-19 pandemic, this is a key time to examine how public health and healthcare systems collaborate to improve population health and build Learning Health Systems. In this knowledge synthesis project, we will conduct a scoping review of the literature on the role of public health in achieving the Quadruple Aim and identify a set of national and international examples that illustrate how collaboration can happen. We will also conduct a national deliberative dialogue, engaging leaders in public health, healthcare system leaders responsible for population health improvement, and policymakers grounded in the shared vision of a Learning Health System. In this multi-part dialogue, we will explore a series of questions: How does the Quadruple Aim fit with public health goals? What are the needs, goals and concerns of public health professionals and organizations? How can population health data support both the Quadruple Aim and public health system performance? What resources are required to enable collaboration and the Learning Health System? This builds on our recent work funded by CIHR to examine public health systems in each province and territory, and past work on Learning Health Systems. This project is a collaboration with knowledge users and the academics who lead the Upstream Lab, the Population Health Analytics Lab and the North American Observatory on Health Systems. The impact of this work will include a detailed understanding of the role of public health systems in achieving the Quadruple Aim and a model of the Learning Health System that includes public health. Our findings will lay the foundation for adequate supports for public health to play this role in Canada, and future research that implements and evaluates this vision.",,-99,Unity Health Toronto,78952.02,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2021 +P26459,460379,Approaches For ThE pRioritization of patients in priMAry care post-COVID To reduce Health inequities (AFTERMATH),"High quality primary care is the cornerstone of strong health systems. The COVID-19 pandemic has significantly altered primary care across Canada. Most offices and clinics rapidly shifted to virtual care, restricted in-person visits or closed their offices, and delayed routine monitoring and lab testing. It is likely health inequities in preventive care activities and chronic disease management widened, but the extent is unknown. AFTERMATH consists of two parts that will occur in tandem. In Part 1, we will use electronic medical record (EMR) data from all seven primary care Practice-Based Research Networks (PBRNs) in Ontario (>1.6 million patients) to examine the impact of the COVID-19 pandemic on gaps in preventive care activities and chronic disease management, and examine inequities by age, sex and gender, income, geography and by chronic disease status, including mental illness. In Part 2, we will conduct a pragmatic cluster randomized controlled trial (cRCT) at the largest PBRN, focused on a population expected to have significant gaps in preventive care activities: adults living with mental illness and at least one additional chronic disease. Our goal is to improve quality of life, reduce gaps in preventive care activities and improve chronic disease management by supporting physicians with a newly developed EMR data driven dashboard plus tailored supports. Our project will result in new evidence on strategies to improve access to and reduce inequities in preventive care. Findings will inform all future efforts to use EMR data drive improvements in primary care beyond the COVID-19 pandemic. If this intervention works, we will be able to rapidly disseminate and scale up in Canadian primary care, building on advances in processing and integrating EMR data into the workflow of clinicians and health organizations.",,-99,Unity Health Toronto,625270.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26462,459248,Beyond Vaccine Nationalism: Advancing ethically-coherent policy action for equitable responses to inherently global health crises,"More than a year into a global pandemic, people around the world continue to experience the burdens and costs of COVID-19 in unfair and unequal ways. Vaccine nationalism involves (mostly rich) countries taking steps to protect their own citizens' access to vaccines. Vaccines remain scarce because of many factors that limit global capacity to manufacture and distribute enough to reach every person who needs it. Many wealthy countries talk about their desire to end the pandemic as soon as possible, but their efforts to protect their own populations added to this scarcity-leaving poorer countries behind. The mismatch between what wealthy countries say they stand for and what they actually do is contributing to even more unfair working and living conditions for the world's poorest populations. This project will bring experts in equity, ethics, policy, and practice together to understand how we can generate fairer global policy solutions that balance the interests and needs of populations around the world. Rather than leaving some people behind, this project will generate learning tools and policy recommendations that can support policy and practice responses that enable all people to move forward to a global pandemic recovery, together. Importantly, what we learn in this project will offer insights and tools that can help us respond to future global health crises.",,-99,University of British Columbia,371540.04,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Research to inform ethical issues,Research to inform ethical issues in the Allocation of Resources | Research to inform ethical issues in Governance,2021 +P26463,468555,Developing Statistical Tools and Visualization Methods for Understanding Heterogeneity in Distributed Networks: Applications to COVID-19 and Diabetes,"Scientists at the Canadian Observational Network for Drug Effect Studies (CNODES) have created ways to combine results from separate Canadian provinces, the United Kingdom, and the United States to rapidly assess the safety and effectiveness of drugs while minimizing the risk of accidentally exposing patient data or jeopardizing patient privacy. Because each province differs from the others, the United States, and the United Kingdom, the best research strategies (as well as the overall safety and effectiveness of drugs) can be very different as well. In 2022, these differences are larger than ever thanks to the ongoing COVID-19 pandemic substantially altering the types of drugs patients start taking and whether they attend in-person office visits with their providers. Currently, however, there are very few ways to understand, document, and communicate these differences. This research project aims to develop new ways for researchers to understand, interpret, and communicate differences in how parts of networks like CNODES (or other studies involving multiple populations) decide which patients receive what treatment, differences in rates of important risk factors and health outcomes, and the extent to differences between populations change research findings and alter treatment effectiveness. These new tools will be tested on data from the United Kingdom's Clinical Practice Research Datalink (CPRD), treating six geographic areas as if they were each contributing data to a distributed network like CNODES. Finally, the tools will be used to study 2019, 2020, 2021, and 2022 data from the CPRD, Ontario, and British Columbia to understand how the timing of lockdowns and other pandemic prevention measures impacted whether patients initiated various drug treatments for high blood pressure, diabetes, and depression, as well as the frequency of various important health outcomes.",,-99,Lady Davis Institute for Medical Research (Mtl),372404.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2022 +P26464,473342,A development platform for mutation-resistant vaccines and antibodies for SARS-CoV-2 future variants,"Globally, as of August 2022, there have been an estimated 600 million cases of COVID-19 worldwide, and over 6.4 million deaths. Novel variants of SARS-CoV-2 virus continue to emerge and escape immunity by either previous infection or vaccination, resulting in repeated infection with potentially serious consequences. In this research program, we will develop rationally designed therapeutics that are robust to mutation of the virus, in preparation for future pandemic waves. We propose to develop both an antibody and a vaccine immunogen that exploit unconventional strategies in order to remain effective in spite of the rapid mutation of the virus. The vaccine candidate is designed to elicit a patient's antibodies to target a portion of the viral protein that is conserved and unlikely to mutate without altering essential functions that would themselves hinder the virus. The antibody is designed to remain effective in blocking the virus from entering cells so long as the virus uses the same cell recognition protein on its entry pathway. Since we know the virus will continue to mutate, it is critical to know how it may mutate to evade existing therapeutics or immunogenic response. We will investigate this question using a ""chimeric"" version of the virus which looks like SARS-CoV-2 on the outside, but is relatively harmless on the inside (a ""sheep in wolf's clothing""). We can induce escape mutations in this chimeric virus by applying selection pressures using either convalescent or vaccinated patient sera, or existing recombinant antibody therapeutics. These escape mutants may share common features with variants of concern in the future. This powerful development platform will provide a strategy for generating pre-emptive therapeutics that can be pivoted to future outbreaks of other novel viruses.",,-99,University of British Columbia,76662.06,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies | Pre-clinical studies | Vaccine design and administration",2022 +P26465,494497,"A platform for developing mutation-resistant vaccines and antibodies for future viral variants, using SARS-CoV-2 as a model","Globally, as of August 2023, there have been an estimated 769 million cases of COVID-19 worldwide, and over 6.95 million deaths. COVID-19 provides a sobering case study of the consequences of insufficient pandemic preparedness. Novel variants of SARS-CoV-2 virus now continue to emerge and escape immunity by either previous infection or vaccination, resulting in repeated infection with potentially serious consequences. All historical precedents indicate that future outbreaks will continue to occur. In this research program, we will pursue a preventative program against future pandemics, by developing rationally designed therapeutics that are robust to viral mutation, and thus effective in preparation for future pandemics. We will develop antibody and vaccine immunogen therapeutics that exploit unconventional strategies to remain effective in spite of the rapid mutation of the virus. We design antibodies that will remain effective in blocking the virus from entering cells so long as the virus uses the same cell receptor on its entry pathway. The vaccine immunogen candidates we design will target a portion of the virus that is conserved and unlikely to mutate because it is functionally necessary. We will test the efficacy of these therapeutics against live SARS-CoV-2 virus infection in mice, where these therapeutics are expected to provide sustained protection against all strains of SARS-CoV-2. We have also developed a safe ""pseudovirus"" platform where the spike protein of the virus can mutate. In our proposed experiments, our therapeutics are again expected to remain effective as the pseudovirus mutates, while conventional therapeutics will be expected to gradually lose efficacy. The above powerful development platform provides a strategy for generating pre-emptive therapeutics that can be pivoted to future outbreaks of other novel viruses. Extending our SARS-CoV-2 studies, we will apply it to other related viruses with pandemic potential.",,-99,University of British Columbia,235388.28,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P26466,430038,Évaluation en temps réel du déploiement de technologies connectées et du partenariat de soins et services dans le contexte de crise sanitaire lié à la COVID-19 - le programme Techno-COVID-Partenariat,"Faced with an unprecedented health crisis, the two institutions that receive the most COVID-19 patients in Quebec have decided to implement social and technological innovations adapted to each stage of the trajectory of COVID-19 patients, from diagnosis to recovery, in order to reduce isolation, maintain the partnership between patients and clinicians and promote the quality and safety of care. Grouped together within the Techno-COVID-Partenariat project, this research makes it possible to evaluate in a real-life care situation how these innovations are implemented, on which dimensions they act and how much they can cost, as well as determine whether factors can explain certain results. The innovations studied focus on (i) the contribution of mobile applications for the maintenance of newly diagnosed patients; (ii) the combination of telephone calls from volunteers to break isolation and the use of different technologies to carry out teleconsultations and telemonitoring; (iii) the adoption of a companion robot to entertain and care for COVID-19 patients hospitalized with psychiatric disorders; and (iv) supporting patients during their transition and return home using COVID-19 patient companions and a remote monitoring platform. The evaluation of these innovations is a unique opportunity to show how virtual health tools can potentially reliably treat thousands of patients over a short period of time while preserving at-risk healthcare workers and ensuring the maintenance of social ties and partnerships. If the results are conclusive, they will accelerate their implementation in other institutions (Canadian and international), not only for COVID-19 but also for any other health problem that could benefit from these technologies and modalities.",,-99,Centre hospitalier de l'Université de Montréal (CHUM),357455.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P26468,476956,Facilitating the implementation of quality standards for youth and family engagement within the community child and youth mental health and substance use health system.,"The COVID-19 pandemic has negatively impacted the mental health and well-being of many young people living in Canada, underscoring the need to address long-standing gaps in the delivery of mental health and substance use health services across the country. Quality standards can help ensure consistent, high-quality care, but they must be supported by people and resources to change the delivery of healthcare services in an impactful way. The meaningful engagement of young people and families in the healthcare sector can positively impact service experiences and outcomes and is considered an essential component of quality standard development and implementation. Since 2020, the community child and youth mental health and substance use health sector in Ontario has been supported by two standards for meaningful youth and family engagement. Evaluation of early efforts to implement these standards points to difficulties in measuring the standards, understanding agency-specific and practical approaches to implementation, and sustaining implementation without significant, specialized support. The proposed project will build on these early efforts by examining (a) the barriers and facilitators to the uptake of youth and family engagement standards, (b) the sector's vision of successfully implementing these standards, and (c) possible intervention strategies to support adoption and use of the standards. Findings will inform practices in effective youth and family engagement, and implementation of standards across Canada. The work will also contribute to the development and implementation strategies for new pan-Canadian standards for mental health and substance use health services for children, youth and families, ultimately supporting long-term transformation and better health outcomes among young people in Canada.",,-99,Children's Hospital of Eastern Ontario Research Institute Inc,147260.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26470,450578,"Understanding and mitigating the impacts of the COVID-19 pandemic on youth, families and schools in remote areas","The COVID-19 pandemic and the resulting measures have had significant consequences on the health of young people and families, as well as on school environments. Despite these difficulties, the containment measures have had some positive impacts for young people and families, such as increased quality time spent with family, reduced stress related to travel and social commitments, and increased parental involvement in their children's school activities. The impacts of the pandemic on young people and families are therefore varied and depend on several vulnerability factors. In this context, this qualitative study will, through 73 interviews, highlight the discourse of young people, parents and school staff members in Saguenay-Lac-Saint-Jean (Québec) on the consequences of the pandemic on their health and their adaptation to it, in light of social, academic and digital inequalities. It will be conducted in collaboration with two school service centres (CSS) in the region through individual (parents) and group (students and school staff) interviews in primary and secondary schools. This project offers a promising avenue to better understand the consequences of the pandemic on the health of school stakeholders in remote regions, a subject that has been little studied to date. It will identify the strategies that seem most effective in addressing inequalities in schools and the consequences of the pandemic. This data can be integrated into the support services offered by schools in order to improve the quality and effectiveness of the support offered to young people and their families during and after the pandemic.",,-99,Université du Québec à Chicoutimi,65902.76,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts,2021 +P26471,460356,Deciphering the impact of aging and inflammation on neurocognitive impairments in people with Post-Acute Sequelae of COVID-19 (PASC),"Inflammation is a key aspect of the disease process in COVID-19. Older persons are at greater risk for severe COVID-19 due to the negative or adverse convergence of aging and inflammation. The consequences of COVID-19 on the brain are uncertain but we know that over 25% of people who recover from COVID-19, subsequently experience brain problems including memory, language, concentration, sleep and mood disabilities (www.cbc.ca/player/play/1970781763780). It is also unclear to what extent brain damage occurs during acute COVID-19 and its contribution to long term consequences of COVID-19, termed 'long covid' or post-acute sequelae of COVID-19 (PASC). Nonetheless, these brain disabilities can prevent people with PASC from returning to work and regular day-to-day activities together with causing depressed mood, social isolation and increased use of the healthcare system. Our proposed research will examine the fundamental disease mechanisms in the brain during COVID-19 using autopsied brain tissues and a mouse model of COVID-19. In people with PASC, we will study the frequency, severity, types of brain function abnormalities using psychological testing. In addition, we will discover risk factors and signs of brain abnormalities measured in the blood in relation to aging and brain resilience or adaptability that can guide diagnosis and treatments. We are a multidisciplinary team and are comprised of early, mid, and senior clinical and experimental researchers with unique expertise in Canada. In fact, our preliminary data show marked inflammation in the brains of humans dying with COVID-19. These proposed studies will discover the disease pathways that cause the brain function abnormalities in people with PASC and will lead to a better understanding of PASC-associated brain problems and new treatment approaches.",,-99,University of Alberta,401380.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26475,438750,Nutrition as Medication: from research to implementation,"Malnutrition and weight loss are endemic in long-term care facilities (LTCFs). Yet their consequences are serious, including an increased risk of mortality and morbidity such as pressure ulcers and respiratory infections. This reality has been exacerbated during the pandemic. LTCF stakeholders report that those affected by COVID-19 have seen their nutritional status deteriorate rapidly. At the same time, non-affected residents have also experienced significant and undesirable weight loss. Interventions to prevent weight loss should aim to increase energy and protein intake. The use of oral nutritional supplements is a common means of achieving this objective. However, actual consumption of these products is rather low. Since 2017, an intervention nicknamed NAM for <> has been developed and tested in LTCFs by our team. This intervention suggests prescribing small doses of an oral nutritional supplement (30 or 60 ml) that are administered like a medication. The effectiveness of NAM has been studied. Preliminary results show a high administration rate (93-95%), a significant improvement in nutritional status and a reduction in pressure ulcers among residents. In follow-up to these results, a guide was written describing the NAM intervention, the principles that frame it, and the suggested strategy for successful implementation in an ESLD. The NAM intervention appears to be a promising practice that could limit, or even prevent, the deterioration of the nutritional status of residents, whether or not they have COVID-19. However, the studies were conducted before the onset of the pandemic and the implementation guide therefore does not take this context into account. Thus, with the aim of better equipping ESLDs during the new wave of COVID-19, our team proposes the dissemination and scaling up of the NAM intervention in ESLDs. Specifically, we propose to: 1) support the implementation of NAM in two Montreal ESLDs; 2) evaluate the implementation of NAM in terms of prescription and administration of treatment; 3) identify the facilitating and constraining factors of NAM implementation; 4) identify the effects of NAM as perceived by stakeholders and relatives/residents; and 5) review the NAM implementation material.",,-99,"CIUSSS du Centre-Sud-de-l'Île-de-Montréal (Montréal, Québec)",18441.12,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Clinical trials for disease management | Indirect health impacts",2020 +P26476,475092,Primary Care Teams Capacity Estimator (CapEs): Synthesizing evidence and developing the CapEs simulation software to support Canadian primary care policy makers and healthcare planners better reason about primary care team capacity in a time of crisis.,"This project is designed to help decision makers and primary care planners better estimate how team based primary care can help address the gaps in primary care in Canada. Primary care is key to sustainable healthcare worldwide. In Canada, due to a number of factors, including the COVID pandemic and increasing burnout, our primary care systems are in crisis. Millions of Canadians without a primary care provider and 40% of family physicians are expected to retire in the next 10 years. Despite increases in medical school enrolment, changes in payment structures, and other incentives, primary care is crumbling. To help address this crisis, provinces are expanding primary care teams to build capacity and address the growing primary care needs of Canadians. However, there is insufficient evidence and a lack of tools to help decision makers and planners reason about how teams address the gaps provincially or locally. This research, part of the Primary Care Team CAPacity EStimator (CapEs) project, seeks to develop some of the missing evidence to guide policy makers and incorporate it into an accessible web application so decision makers and planners can use the evidence while planning team-based primary care. Specifically, this research will 1. Co-develop and validate the evidence of how different providers (nurses, social workers, pharmacists, etc.) add capacity to a primary care team. We will use a combination of literature review and modified Delphi with experts. 2. Translate that newly synthesized evidence into the CapEs web application, that will allow 3. Share the CapEs web application through various webinars and training opportunities with primary care planners and decision makers in multiple provinces. An initial version of CapEs software has been developed at the Primary Care Innovation Support Unit in BC. The multidisciplinary research team has extensive experience in team based care planning including at: clinical, research, and policy levels.",,-99,University of British Columbia,108470.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Social Workers | Health Personnel | Hospital personnel | Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research | Research on Capacity Strengthening",Indirect health impacts | Health workforce | Individual level capacity strengthening,2022 +P26481,451461,Host cell-derived tissue factor as a broad-spectrum basis for viral pathology and infection,"Well-balanced blood clotting is essential for health and has life-threatening impact when tipped off-balance. Many viruses are known to trigger an infected person's blood clotting system and cause a wide range of clotting-related clinical problems; from heart disease to bleeding. The processes used by the virus to cause these diseases are poorly understood. Using the oral herpes virus (HSV1) as a model virus, our lab has shown that these germs hijack clotting activators to increase infection. To understand how, the current proposal focuses on our discovery that a protein called, tissue factor, is integrated into the virus' surface. Tissue factor is found within our cell membranes and is essential for life. Many viruses are covered with a membrane, called an envelope, which is acquired from our infected cells and can therefore contain tissue factor. Why is tissue factor important? Because it is the initiator of blood clotting and it also alters the function of cells. Here we propose to expand our findings in HSV1 and extend our knowledge to HIV and dengue virus, both major global problems. We will take biochemical and animal approaches to test our ideas, which have already revealed possible strategies to treat these virus infections. In addition to these viruses, many others that burden healthcare systems world-wide have an envelope, such as influenza, Ebola, hepatitis C and Zika viruses. The five virus types we have investigated to date all have tissue factor, suggesting that any virus with an envelope can acquire tissue factor. Since cells containing tissue factor are found throughout the body and are infected by many types of virus, we anticipate that targeting tissue factor found on the surface of viruses will allow us to treat a wide-range of viral infections and fill a serious deficiency in global healthcare.",,-99,University of British Columbia,897133.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae | Flaviviridae | Orthomyxoviridae,Unspecified,,,,,,,,Ebola virus disease | Zika virus disease | Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P26483,471247,The function and regulation of tissue resident alveolar macrophages turnover by host and environmental factors during homeostasis and in infections,"With 3 million deaths per year, lower respiratory tract infections are the leading infectious cause of death and the fifth-leading cause of death overall. Therefore, it is extremely important to understand how our respiratory immune system works and potentially discover ways to therapeutically improve lung capacity. The majority of immune cells living in the alveoli are resident alveolar macrophages (resident AMs). They constantly ""crawl"" in the alveoli and clear bacteria we breathe in to keep our lungs clean. It is now well known that there is a gradual replacement of AMs by monocytes that then assume the role of AMs (replacement AMs). I am interested in understanding if there is an advantage to AM turnover, or whether this is simply a negative side effect of ageing. A further question is whether this turnover is expedited by factors including seasonal flu, COVID-19 or environmental factors including pollutants, silicosis and other contaminants. We now have a mouse in which the replacement AMs are fluorescent red while the resident AMs are blue. This allows us to systematically examine how these two different AM populations behave (e.g. crawling, bacterial clearance) inside the lungs of living mice. To explore the environmental factors on 1): resident AM turnover; and 2) the behaviour of AMs, we will examine mice in a completely germ-free environment that have no microbes at all and mice that are co-housed with wild mice so they have a very robust microbiome with numerous infections. Finally, BCG vaccine induces ""trained immunity"" which makes immune cells respond more robustly to all infections and we will test if AMs can be trained to enhance defenses against lung infections caused by bacteria, flu and SARS-CoV-2. The outcome of this study will provide unprecedented insights into how host and environmental factors imprint AM function and how the underlying mechanism(s) may be used to guide the development of novel therapeutic strategies for lung infections.",,-99,University of Calgary,107326.88,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis | Immunity",2022 +P26485,443547,The work-family interface as a gendered social determinant of mental health,"The COVID-19 pandemic has highlighted the gender differences that persist in work-life balance, despite years of social progress in the pursuit of equity in this regard. However, the majority of studies that have focused on these differences to date fail to distinguish the gendered stressors and resources that emerge from the articulation of two major spheres of life: work-family conflict (WFC) and work-family enrichment (WFE). WFC and WFE are bidirectional since work can interfere with family or enrich family life and family can interfere with work or enrich work life. The latter have distinct antecedents and consequences. In addition to being determinants of several manifestations of physical and mental health, both directions of WFC and WFE are suspected of being vectors of mental health inequalities between women and men. Considering that 55% of parents of children aged 0 to 5 experience moderate or high work-family conflict, mitigating this conflict is a significant challenge for businesses and various levels of government in Canada.",,-99,McGill University,288682.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26486,450606,Work-family conflict as a gendered social determinant of parents' and children's mental health following the COVID-19 pandemic,"The COVID-19 pandemic and the health measures to contain it have had significant effects on the mental health of children and their parents. They have also highlighted the gender differences that persist in work-family balance, despite years of social progress in the pursuit of equity in this regard. However, the unequal distribution of difficulties in balancing work and family can not only affect several manifestations of workers' physical and mental health, but also the physical and mental health of their children. However, the impact of work-family balance on the mental health of children in Quebec following the pandemic remains unexplored. Current data also do not allow us to distinguish the gendered stressors that emerge from the articulation of two major spheres of life: work and family. Work-family conflict (WFC) is bidirectional since work can interfere with family and family can interfere with work. Considering that 55% of parents of children aged 0 to 5 in Quebec experienced moderate or high work-family conflict before the COVID-19 pandemic, mitigating this conflict and the resulting inequalities is a significant challenge for businesses and the various levels of government in Canada in order to promote the mental health of parents and their children.",,-99,McGill University,120626.15,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26487,447359,Identifying Service Gaps in Virtual Palliative Care to Inform Health Policy Across Canada,"IMPORTANCE: There are over 280,000 annual deaths in Canada, and relatively few home- based providers to deliver care to the majority who prefer to die there. The COVID-19 pandemic posed many challenges for healthcare delivery. This was especially important for those at the end of life who overwhelmingly prefer to die at home with the support of home-based palliative care. The use of virtual palliative care was rapidly upscaled across the healthcare system to address support gaps for patients while preventing transmission of COVID-19. However, there are concerns that certain people are not be able to use virtual palliative care, especially those that are older, have lower income or live in rural areas. This created a unique opportunity to study if virtual palliative care can improve how people die and their ability to access high quality end of life care. METHODS: We will use validated administrative data in Canada to conduct a population-wide study investigating increases in the volume of virtual palliative care, who received it, and where they died during and following the pandemic. We will align the findings from our analyses of big data using interviews with palliative care providers and health administrators to understand their perceptions on how policy initiatives related to virtual palliative care inlfuence disparities in access. RELEVANCE AND IMPACT: The successful adoption of virtual palliative care in the post pandemic era will rely on evaluation of its impact to ensure it is both accessible to all patients and effective in improving care at the end of life. Our partnerships with key stakeholders and decision-makers will inform the optimization of this rapidly emerging care model, align it with patient preferences to improve population health, and ensure its sustainable delivery across the healthcare system.",,-99,Sinai Health System (Toronto),119166.72,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Infection prevention and control | Secondary impacts of disease, response & control measures | Health Systems Research",IPC in health care settings | Indirect health impacts | Health service delivery,2021 +P26488,448924,Improving the recognition and care of patients with long-term health complications of COVID-19,"IMPORTANCE: More than one year into the COVID-19 pandemic, clinicians and researchers are learning that many patients who were infected with COVID-19 develop chronic conditions that negatively affect their overall health. This may occur in older adults with multiple prior chronic conditions, or in younger adults who were relatively healthy prior to infection with COVID-19. Presently, there is limited understanding of how long-term post-COVID-19 conditions and a person's prior chronic conditions impact their overall use of the healthcare system, their chances of dying and the types of care they receive, including at the end of their life. This project aims to study and predict the development of clinical conditions, the types and quality of care patients receive in hospital, their long-term patterns of healthcare needs including end of life care, and their risk of death following their discharge from hospital after COVID-19 infection. METHODS: GEMINI has built a data platform that collects and harmonizes patient data from all medical and intensive care admissions at ~30 hospitals across Ontario (representing ~65% of the province's patients). We will use rich clinical data and leverage advanced methods in machine learning to study healthcare delivery and clinical outcomes up to one-year after initial hospitalization for COVID-19. Our partnerships with key knowledge users helped inform our research questions and will allow immediate application of our findings to directly support Canada's ongoing response to the pandemic. IMPACT: Improving our understanding and recognition of patients with post-COVID-19 conditions will allow us to identify gaps in care. We will focus on defining high-quality care that can enhance recovery, improve clinical outcomes and improve the quality of end-of-life care in patients who die by minimizing inequities in access to this care.",,-99,Sinai Health System (Toronto),397220.82,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health service delivery,2021 +P26489,447269,Identifying Disparities in Equitable Access to Virtual Palliative Care,"IMPORTANCE: There are 280,000 Canadian adults who die each year and relatively few providers to deliver care to the majority who prefer to die at home. The COVID-19 pandemic posed many challenges for healthcare delivery. This was especially important for those at the end of life who overwhelmingly prefer to die with the support of home-based palliative care. The use of virtual palliative care was rapidly upscaled across the healthcare system to address support gaps for patients while preventing transmission of COVID-19. This created a unique opportunity to study who received virtual palliative care and who did not, and if virtual palliative care can improve how people die and their ability to access high quality end of life care. METHODS: We will use validated administrative data at ICES in Ontario to conduct a population-wide study investigating increases in the volume of virtual palliative care, who received it, and associated outcomes during and following the pandemic. We will align the findings from our analyses of big data using interviews with patients, caregivers and palliative care providers to understand their experience and the perceived facilitators and barriers to its use. RELEVANCE AND IMPACT: The successful adoption of virtual palliative care in the post pandemic era will rely on evaluation of its impact to ensure it is both accessible to all patients and effective in improving care at the end of life. Our partnerships with key stakeholders and decision-makers will inform the optimization of this rapidly emerging care model, align it with patient preferences to improve population health, and ensure patients have access to the best possible end of life care when and where they need it.",,-99,Sinai Health System (Toronto),119166.72,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Infection prevention and control | Secondary impacts of disease, response & control measures | Health Systems Research",IPC in health care settings | Indirect health impacts | Health service delivery,2021 +P26490,494291,Nirmatrelvir/ritonavir (Paxlovid) in the prevention of long-term cardiovascular outcomes: The paxloviD Effectiveness For the prEvention of loNg coviD (DEFEND) clinical trial.,"The paxloviD Effectiveness For the prEvention of LoNg coviD (DEFEND) clinical trial will look to see if giving Paxlovid to people when they are first sick in hospital with COVID will lead to fewer deaths, heart problems, strokes, diabetes, or blood clots in the year afterwards. COVID's effects don't end when the infection does. Long COVID, also called Post-Acute Sequelae of COVID, causes a range of disabling symptoms, and serious health conditions. Paxlovid is a mixture of 2 antiviral medications already used to prevent severe illness as a result of COVID infection. We want to see if Paxlovid also prevents long COVID. No one knows if Paxlovid will do this, which is why we need to study it in a clinical trial. We will study adults who are sick enough to need admission to hospital and who test positive for COVID. We won't include people who are so sick with COVID that they need other drugs like steroids. This lets us look at only the effect of Paxlovid in the prevention of long COVID. This trial is called a pilot. It's focus is studying if we are able to complete a larger future trial. When a patient agrees to be participate, they will be randomly get Paxlovid or pills that look and taste the same but do not contain any medication (called placebo). We will check how many people successfully participated in the pilot over 1 year. After people receive treatment, we will check if any of them died or were newly diagnosed with heart problems, stroke, diabetes, or blood clots in the year afterwards. If people already had these health issues when they were hospitalized, we will check if any of these health issues got worse in the year after they had COVID. If we can successfully include enough people in the pilot, we can study if these health problems are reduced in people who got Paxlovid compared to those who did not. This information could change lives, change how COVID is treated, and change the odds of getting long COVID.",,-99,Sinai Health System (Toronto),73558.84,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Post acute and long term health consequences | Clinical trial (unspecified trial phase) | Prophylactic use of treatments,2023 +P26493,480917,Co-Designing a National Webinar Series to Improve Young Canadians' Awareness and Access to Mental Health and Addiction Services since COVID-19,"Purpose: The COVID-19 pandemic has had a tremendous impact of the mental health and/or addictions of young people, what services or supports are available to them, and the ways they can access services and support. Webinars and 'peer experiences' as valuable strategies to improve the sharing of information and may help young people become more aware of when, how or where to get help. Putting the needs and perspectives of young people and caregivers first, we will organize and conduct a set of virtual meetings with diverse partners to plan for an open access, national webinar series to promote young Canadians' awareness and access to mental health and/or addiction services since the COVID-19 pandemic. Aims and activities: We will bring together various perspectives and the best available evidence from research, lived experience, and existing services and resources to plan this webinar series. Aims of the meeting will be to build relationships for planning the national webinar series, identify webinar topics and presenters and create a schedule for the webinars, and prepare for a future funding application to support the launch of the webinar series. Significance: The changes in young people's mental health and/or addiction since the pandemic, and the services that support them, are widespread and significant. Despite longstanding issues with services users' awareness and access to mental health and/or addiction care, now is an essential time to bring the public 'up to speed' on the services for young Canadians as reflected in their current state. This webinar series is an important pathway for scaling young people's confidence, ability and awareness to promote their own health, interact effectively with services, and be active partners in managing their own mental health and/or addictions.",,-99,Children's Hospital of Eastern Ontario Research Institute Inc,17660.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Communication | Indirect health impacts,2023 +P26494,475178,The Impact of Post COVID-19 Condition on Nursing Labour Supply,"Our analysis uses a combination of real-world data and modelling to determine: (1) the current state of nursing supply, (2) how it will change due to Post COVID-19 Condition (PCC) and (3) policy options for addressing those impacts. Nurses included in this analysis are Registered Nurses, Licensed Practical Nurses, Nursing Attendants, Nurse Practitioners and Registered Psychiatric Nurses. We will use Alberta as the setting of our research due to the availability of data and to compliment ongoing research estimating the demand for healthcare labour in Alberta due to PCC and the effect of COVID-19 vaccines on this demand. Our analysis is comprised of three phases. First, we will estimate the current nursing supply in Alberta. Second, we will determine how nursing supply may change in the future due to the ongoing impact of PCC by building upon an existing model that captures the impact of PCC on occupational time lost due to ongoing symptoms. Third, we will test several policy alternatives to evaluate options for limiting the impact of PCC on nursing supply in Alberta. We will expand the analysis to identify inequity in current supply and changes to supply based on PCC across urban and rural areas. Findings from this analysis will provide a basis for evaluating these questions across Canada, as well as information on relevant policy alternatives for all provinces facing nursing labour supply issues.",,-99,Institute of Health Economics (Edmonton),54625.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26498,448836,Clinicopatholgical correlates of long COVID and potential interventions for improving the quality of life,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus to jump species to humans in the past 10 years and is the causative agent for COVID-19. While the mortality rate is the lowest for SARS-CoV-2 when compared to SARS-CoV and MERS- CoV, its high infectivity has made it cause the worst pandemic in the past 100 years after the Spanish flu. Majority of COVID-19 infections are asymptomic and relatively mild, with recovery typically within 2-3weeks, but 1-3% of infected individuals develop severe illness, which is postulated to be related to both an overactive immune response and viral-induced pathology. Unknown proportion of all the infected individuals after recovering from the initial illness, develop a so-called ""long COVID,"" in which they experience persistent symptoms not necessarily related to the infection directly. The syndrome appears to affect those with mild as well as moderate-to-severe disease. The incidence, natural history and etiology of these symptoms is currently unknown. It is not know whether long-Covid-19 is observed only in individuals with primary infections, or it can also develop in vaccinated individuals who are infected. In this study we will address the characteristics of the immune responses in infected- recovered individuals who experience or not long Covid-19 and in vaccinated individuals. These studies will pave way for future programs that target Covid-19.",,-99,Université de Sherbrooke,389277.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26499,494273,Tailored exercise interventions to improve the quality of life in individuals with post-COVID-19 condition: The impact on patient's functionality and their immune and plasma proteome parameters,"At the tail-end of the COVID-19 pandemic, a significant number of infected-recovered individuals have developed long COVID, a condition which affects their well-being and their ability to carry out tasks that they were easily doing before the pandemic. There are some indications in the published literature that low to moderate exercise regimen tailored to the capacity of the individual, can help improve their condition. In this study we will characterize the exercise program and determine how exercise benefits a significant proportion of those affected with long COVID. We will study the effect of exercise in infected individuals with long COVID and follow them over one year to determine the long-term benefits of exercise. We will also analyze their immune responses, oxidative stress responses and identify biomarkers in the blood that are modulated by the exercise.",,-99,Université de Sherbrooke,73558.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P26500,460461,Evaluation of Virtual Care for Rapid Access Clinic - Low Back Pain: Patient and Healthcare Provider Perspectives Across Ontario,"Background: Low back pain (LBP) is the most common cause of chronic pain and disability around the world. Access to evidence-based LBP care from providers that work together and put the patient at the center of care has been a longstanding global challenge that has only been made worse by the COVID-19 pandemic. The Rapid Access Clinics - Low Back Pain (RAC-LBP) program in Ontario is designed to assess, individualize and coordinate care for patients with persisting LBP. The RAC-LBP supports over 6400 primary care providers across the province, receives approximately 1500 referrals per month and has seen over 30K patients since 2018. As a result of the pandemic the program had to shift to virtual (video based) care for most patients. Although the program has now returned to more in-person care, many patients have reported a preference for virtual care. We aim to study the impact of combining in-person and virtual care on the preferences and experience of both patients and providers in the provincial RAC-LBP. Methods: We propose collection of data regarding the likes and dislikes of in-person and virtual care from patient and frontline providers focused on the care of LBP. Data will be obtained by surveys and by one-on-one interviews. After final review of our results by patients, providers, researchers, managers and payers of healthcare, the key perspectives of patients and providers regarding a balanced use of both in-person and virtual care will be presented. Impact: Identifying the best use of both in-person and virtual care to meet the individual preferences and needs of patients will improve the experience of both patients and providers. Finding the right balance of in-person and virtual care for LBP will help the healthcare system be more efficient. In addition, the lessons learned from this study may help in guiding the balanced use of virtual care in other chronic conditions such as diabetes or arthritis.",,-99,University Health Network (Toronto),78976.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26506,495597,Advancing Virtual Care in Stroke Rehabilitation through the TeleRehabilitation with Aims to Improve Lower extremity recovery post-stroke (TRAIL) program,"A focus of stroke rehabilitation is on the recovery of lower-extremity limitations via exercise-based physical therapy, but many individuals report unmet rehabilitation needs due to barriers with accessing stroke care. The emergence of telerehabilitation presents an opportunity to expand the continuum of stroke recovery, especially since the COVID-19 pandemic. However, our knowledge of the effectiveness of using telerehabilitation for the delivery of exercise interventions for lower extremity recovery is limited, thus highlighting the need for clinical research. This 60-minute symposium will bring interested stakeholders together to learn about and discuss: 1) Emerging telerehabilitation research to address the unmet lower extremity rehabilitation needs of individuals with stroke 2) Exploring qualitative learnings on the experiences of an exercise-based telerehabilitation program among individuals with stroke 3) Involving patient partners to help advance the delivery of telerehabilitation interventions to individuals facing barriers to accessing stroke rehabilitation services 4) Optimizing the provision of telerehabilitation using innovative technologies",,-99,University of British Columbia,1103.38,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26507,481136,Impact of host responses on mpox pathogenesis and tecovirimat efficacy in the Collaborative Cross mouse model of genetic diversity,"The host response to infection is a critical determinant of disease severity. However, host responses that dictate the outcome of mpox (monkeypox) virus disease are largely unknown. Furthermore, although antiviral therapies can effectively treat mpox infection, it is not known how they can be optimally used to resolve disease symptoms, or the role of the host response in antiviral efficacy. Current experimental models for studying host responses to mpox or treatment with antiviral drugs are not genetically diverse and thus are unable to faithfully reproduce these responses in human patients, which limits their utility in addressing these knowledge gaps. We propose using the Collaborative Cross, a panel of mice with increased genetic diversity, to study the host responses to infection that lead to distinct mpox disease outcomes. We will screen a panel of genetically diverse mice to identify those that develop different presentations of mpox disease severity, and then investigate host responses in affected tissues that lead to distinct outcomes. We will also test the ability of tecovirimat (TPOXX), an antiviral drug used to treat mpox, to ameliorate mpox disease features such as skin lesions when treatment is initiated at different times following infection. We will also evaluate host responses associated with effective TPOXX treatment, as well as assess the risk of TPOXX resistance. This proposed project will provide crucial insight into the role of the host in determining mpox disease severity, as well as optimize using TPOXX to treat mpox most effectively and with the greatest benefit to patients. In addition to filling critical knowledge gaps, this project will also produce a model that will be an invaluable resource to the scientific community for both studying mpox infection and disease and developing improved vaccines and therapies.",,-99,University of Saskatchewan,375198.56,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Research for enhanced understanding of the disease | Promote improved understanding of the disease (including evidence synthesis) | Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course | Development of equitable, accessible, safe & effective therapeutics",Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease models | Disease pathogenesis | Supportive care, processes of care and management | Pre-clinical studies",2023 +P26508,477294,Host cell reorganization by SARS-CoV-2,"Each cell in the human body is organized into distinct subcompartments called organelles. Organelles compartmentalize and organize specific groups of proteins to perform unique biological functions (e.g. protein synthesis, protein folding, or the synthesis, storage or breakdown of fatty acids). When a virus infects a cell, it can ""reprogram"" the host cell organelle machinery - essentially remodelling the host cell to create a highly efficient ""virus factory"". Our project aims to shed light on how human organelles are reprogrammed and remodeled in response to infection by the coronavirus SARS-CoV-2. We have developed highly specialized methods to track protein localization in living human cells (BioID Cell Mapping), and will use this technology to monitor a number of human organellar proteins in SARS-CoV-2 infected and uninfected cells. This work will provide much needed knowledge on how cellular organelles are remodeled in response to coronavirus infection, and identify new therapeutic targets for the treatment of viral infections.",,-99,Princess Margaret Cancer Centre (Toronto),73103.45,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P26512,475490,Enhancing access and engagement in pediatric telerehabilitation for children with disabilities and their families,"For children with disabilities, receiving therapy services is important to supporting development and participation. In Ontario, publicly-funded children's therapy services are offered through organizations called Children's Treatment Centres (CTCs). Prior to the COVID-19 pandemic, appointments at CTCs primarily occurred in person. COVID-19 restrictions meant that CTCs had to pivot and offer services remotely using telerehabilitation technologies. Current data shows that children with disabilities and their families experience barriers in attending and participating in telerehabilitation appointments and may need supports to ensure that these services are accessible. This research project will use an experience-based co-design approach, where families, clinicians and CTC leadership will work together to improve how families receive telerehabilitation services. Creative solutions to improve access and engagement in telerehabilitation services will be developed together and implemented to ensure that all families can use the services they are eligible for and to improve children's functional outcomes. The solutions developed will be evaluated in an Ontario CTC and shared with a network of experts across Canada working in children's rehabilitation practice and research.",,-99,McMaster University,77083.46,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26514,458293,Unmet needs of immigrant older adults after discharge from hospital with delirium: Using administrative data to explore practice patterns and long-term adverse health outcomes,"Older Canadians represent over 40% of hospital admissions and are at increased risk of experiencing hospital related harms. One of these harms is delirium, which is a syndrome of new confusion that is common and affects up to 50% of hospitalized older patients. It is important because it increases the risk of subsequently developing dementia, being admitting to a long-term care home and even dying. Immigrant older adults may do worse after discharge due to a number of risk factors such as low income, systemic racism, and language barriers. This could lead to differences in the care they receive including increased prescription of harmful medications, less access to home care, and less follow up visits with doctors. Limited visits with friends and relatives due to COVID-19 social distancing measures may have exacerbated these issues because immigrants often rely heavily on family members for support. This proposal will use linked health databases to study the care that immigrant older patients with delirium receive in Ontario. We will report the occurrence of delirium during a hospital admission for a medical or surgical reason among immigrant and non-immigrant patients over the age of 65. We will look at the differences in how delirium is managed including who is seen by a delirium specialist and who gets discharged with harmful medications. We will examine the adverse outcomes after a person is discharged including coming back to hospital, developing dementia, or moving to a long-term care home. We will study how antipsychotic prescriptions changed during the COVID-19 pandemic and compare differences in these changes by immigrant status. We anticipate that immigrant older adults will receive more antipsychotics, less home care and have more long-term unfavorable outcomes. Understanding the unmet needs of immigrant older adults after delirium will help the healthcare system implement interventions to better support patients and families.",,-99,University of Toronto,84625.02,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Internally Displaced and Migrants | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26515,457572,Unmet needs of immigrant older adults after discharge from hospital with delirium: Using administrative data to explore practice patterns and long-term adverse health outcomes,"Older Canadians represent over 40% of hospital admissions and are at increased risk of experiencing hospital related harms. One of these harms is delirium, a severe neuropsychiatric syndrome characterized by an acute onset of confusion. Delirium affects up to 50% of hospitalized older patients and is associated with serious consequences including dementia, admission to long-term care and death. Immigrant older adults may be at greater risk of poor outcomes after discharge as a result of insufficient health services and supports. The experience of low income, systemic racism, and language barriers may lead to inequitable care including increased prescription of harmful medications, and less access to home care or follow up. The hospital visitor restrictions employed during the COVID-19 pandemic may have further widened these gaps as immigrant older adults often have a greater reliance on family members for support. There is currently a lack of research exploring the post-discharge period after delirium and the differences in care and outcomes for immigrant populations. My thesis proposal will use large health databases to compare the practice patterns and long-term adverse outcomes after discharge from hospital with delirium between immigrant and non-immigrant older adults. We will investigate long-term adverse outcomes including a new diagnosis of dementia. We will explore changes in antipsychotic prescriptions during the COVID-19 pandemic and compare differences by immigrant status. We will examine the predictors of long-term care home admission including social risk factors such as sex, income, and immigrant status. We anticipate that immigrant older adults will receive more antipsychotics, less support after discharge and have more long-term harmful outcomes. Understanding the unmet needs of immigrant older adults after delirium will assist clinicians, researchers, and policy makers to implement interventions to better support patients and families.",,-99,University of Toronto,120892.88,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Internally Displaced and Migrants | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26516,475745,Unmet needs of immigrant older adults after discharge from hospital with delirium: Using administrative data to explore practice patterns and long-term adverse health outcomes,"Older Canadians represent over 40% of hospital admissions and are at increased risk of experiencing hospital related harms. One of these harms is delirium, which is a syndrome of new confusion that is common and affects up to 50% of hospitalized older patients. It is important because it increases the risk of subsequently developing dementia, being admitting to a long-term care home and even dying. Immigrant older adults may do worse after discharge due to a number of risk factors such as low income, systemic racism, and language barriers. This could lead to differences in the care they receive including increased prescription of harmful medications, less access to home care, and less follow up visits with doctors. Limited visits with friends and relatives due to COVID-19 social distancing measures may have exacerbated these issues because immigrants often rely heavily on family members for support. This proposal will use linked health databases to study the care that immigrant older patients with delirium receive in Ontario. We will report the occurrence of delirium during a hospital admission for a medical or surgical reason among immigrant and non-immigrant patients over the age of 65. We will look at the differences in how delirium is managed including who is seen by a delirium specialist and who gets discharged with harmful medications. We will examine the adverse outcomes after a person is discharged including coming back to hospital, developing dementia, or moving to a long-term care home. We will study how antipsychotic prescriptions changed during the COVID-19 pandemic and compare differences in these changes by immigrant status. We anticipate that immigrant older adults will receive more antipsychotics, less home care and have more long-term unfavorable outcomes. Understanding the unmet needs of immigrant older adults after delirium will help the healthcare system implement interventions to better support patients and families.",,-99,"Women's College Research Institute (Toronto, Ontario)",660.72,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Internally Displaced and Migrants | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26519,474641,Development of a conditionally replicating vaccinia virus platform As an alternative to Modified Vaccinia Ankara for cancer immunotherapy and vaccine production,"Supervisors: John Bell & Carolina Ilkow, uOttawa The COVID-19 pandemic demonstrated the importance of flexible, readily available, and local vaccine platforms in the event of another potential viral infection. The development of improved vaccine platforms is not only essential for the prevention of infectious diseases, but is also being considered as a potential cancer treatment. As cancer is the leading cause of death in Canada, these technologies can vastly improve the standard of care in the country and pave the way for a substantial reduction in the number of cancer-related deaths. Vaccinia Virus was used to eradicate smallpox more than a century ago, and its modern descendants have been improved for greater safety and used to develop vaccines for other infectious diseases, such as the recent outbreak of monkeypox. Nonetheless, both the large-scale production and the immune response to these vaccines have significant room for improvement. We have developed a novel platform based on the vaccinia virus to address these issues. This platform has the potential to overcome the challenges associated with the production, capacity, and stability of current vaccines, and will be engineered for higher immune activation to be administered in a single dose. First, we determined the platform's safety in immune-deficient mouse model; we did not observe any severe side effects or significant weight loss. Then, we confirmed that our platform generated high levels of SARS-CoV-2 proteins. In the next step, we will modify the platform to express antigens from multiple strains of SARS-CoV-2 to demonstrate vaccination against multiple strains. In addition, using colon cancer and skin cancer mouse models, we will evaluate the therapeutic efficacy of our platform when expressing tumor antigens. Overall, we hypothesize that our new platform can serve as a safe and effective vaccine platform for infectious diseases and cancer treatment.",,-99,University of Ottawa,110119.22,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2022 +P26522,466929,Telehealth Intervention Program for Older Adults (TIP-OA): Predictors of treatment response,"Prior to COVID-19, psychiatric disorders affected over 10;15% of older adults (1,000,000 Canadians aged 60+) costing $15 billion/year. The pandemic has increased social isolation and limited resources. We developed an innovative volunteer-based Telehealth Intervention Program for Older Adults (TIP-OA), to improve mental health in older adults. Volunteers provide weekly phone calls to older adults (have served 700+ older adults). There is limited data about volunteer-based phoning programs' real-world effectiveness and predictors of response. To help maximize the programs benefits, and identify individuals needing more support this study aims to identify predictors of treatment response based on participant baseline risk ratings (green: low risk, orange: medium risk, red: high risk) and demographic characteristics. Our primary aim is to identify whether baseline risk level is associated with improved mental health outcomes at 8-week follow-up for stress, depression, anxiety, and COVID fear. Our secondary aim is to identify whether baseline demographic characteristics (age, gender, neighbourhood, etc.) are associated with improvement in mental health outcomes. We anticipate that TIP-OA will be beneficial for improving stress, depression and anxiety symptoms, and fear of COVID over 8-weeks in higher baseline risk level participants. If successful, our studys potential scientific findings will allow us to 1) further refine the intervention and focus future related interventions to patient populations who could benefit most, 2) be a stepping stone for other telehealth and digital health interventions for older adults, and 3) translate these findings to the application and further development of TIP-OA or related interventions on a larger scale.",,-99,McGill University,13724.56,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions | Communication | Policy research and interventions,2021 +P26523,475810,"Trauma- and stressor-related symptom trajectories during a pandemic: stress, trauma, resilience and service use.","The COVID-19 pandemic has confronted individuals to various stressors, some traumatic, others not. According to meta-analytic data, an average of 18% prevalence rate of trauma- and stressor-related symptoms were found in international samples. However, no studies have yet investigated the long-term impacts of such symptoms. My PhD project aims to study the longitudinal trajectories of symptoms of trauma- and stressor-related symptoms among Canadians, identify factors related to their development overtime, and characterize Canadian mental health service use. To achieve this aim, I will be using both online self-report surveys and structured diagnostic interviews to document the longitudinal course of these symptoms, to explore the various factors that may influence the development of disorders, and to explore service uses. The COVID-19 pandemic has brought unprecedented challenges both for people and society. Its long-term effect on mental health is still unknown, my PhD project will provide important information for healthcare providers and policy makers to identify both the consequences of the pandemic and suitable mental health interventions for Canadians.",,-99,McGill University,77083.46,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26531,460318,Analyse des trajectoires professionnelles des infirmières durant la crise sanitaire : Pour des stratégies visant à optimiser la rétention des infirmières et la qualité des soins,"Context: In Canada as elsewhere, certain groups of individuals have been disproportionately affected by the pandemic. This is the case for nurses, who were highly mobilized due to the essential nature of their services. As direct witnesses to the effects of the pandemic, they have dealt with unprecedented administrative measures aimed at ensuring access to health services and extremely difficult working conditions. Some nurses have left the health network during the pandemic, while others, with potentially different characteristics, have continued their commitment or have returned to the profession. However, what characterizes these different professional trajectories is poorly understood. Objectives: 1) Describe the professional trajectories of nurses during the COVID-19 pandemic and identify their determinants; 2) Explore the adaptation strategies used by nurses in these trajectories, and those they would like to see implemented. Methods: An explanatory sequential mixed study is proposed. Phase 1: A provincial survey will be conducted with a representative sample of nurses mobilized during the pandemic. This survey will identify and describe the professional trajectories of these nurses and their determinants. Phase 2: A qualitative ""experience mapping"" study will be conducted with a maximum variation sample of nurses who participated in Phase 1 and contrasting the trajectories and determinants identified. The mappings, from focus groups, will explain the results of the survey and determine adaptation strategies. An integrated knowledge transfer approach supports both phases of the study. Contributions: This project aims to create strategies by and for nurses to address the long-term impacts of COVID-19 on nursing staff and the public.",,-99,Université de Sherbrooke,290042.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +P26532,486203,Étude de la relation entre l'alimentation locale et la qualité globale de l'alimentation au Québec,"Since the start of the COVID-19 pandemic, the Quebec government has encouraged local eating, that is, it encourages the population to eat food that has been produced in the province of Quebec. Obtaining food from here certainly benefits Quebec agricultural producers and the Quebec economy. Indirectly, the government also encourages the consumption of local foods in the hope of improving the quality of the population's diet. Certain scientific studies indeed suggest that ""eating locally"" would be associated with better health. However, no study yet demonstrates with certainty that ""eating local"" is really associated with a healthy and nutritious diet. Currently, healthy eating is a very important issue since many deaths from heart disease, diabetes and cancer are caused by poor diet. It is therefore essential to better understand the link between local food in Quebec and healthy eating, which is the objective of the research project. The project will be carried out using a questionnaire on the purchasing habits of local food products, which will be distributed to participants in NutriQuébec, a Quebec study which studies the lifestyle and diet habits of several thousand Quebecers. and Quebecers. The results of this project will help better guide future public health recommendations in order to better guide the population regarding healthy eating in Quebec and Canada.",,-99,Université Laval,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26533,466232,The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial,"Acute hypoxemic respiratory failure (AHRF), or acute breathing problems, are one of the most common reasons to require hospital admission, or in the most severe cases, admission to the intensive care unit (ICU) for advanced oxygen support. AHRF has multiple causes including pneumonia (COVID or bacterial), aspiration, or even illness in other organs of the body (such as sepsis or pancreatitis) which lead to lung inflammation. Corticosteroids, a group of immune suppressing drugs, have been investigated as a potential therapy for AHRF. Smaller studies have shown benefit of corticosteroids in hospitalized patients with severe pneumonia and in those with a form of severe ARF called ARDS (acute respiratory distress syndrome). Despite this, clinical practice remains varied. Dexamethasone, a type of corticosteroid, was one of the first therapies to show benefit in hospitalized patients with COVID-19 and has now become the standard of therapy in this population. Whether this is also helpful for other causes of ARF remains unclear. Another really important question is how long to treat with corticosteroids in patients with ARF. The largest of the COVID studies used a short course of 10 days, but uncertainty remains, especially if a patient is not improving after 10 days of treatment. We propose to answer two questions within the same research platform. The platform (called PRACTICAL) aims to study many different interventions for treating ICU patients with AHRF. Within this platform, we propose to study corticosteroids: 1) in patients with non-COVID AHRF requiring advanced oxygen support, 2) in patients with AHRF from COVID or non-COVID who have already been treated with a short course of corticosteroids and are still requiring advanced oxygen support, examining the role of extending the duration corticosteroids. The main outcome to be studied will be mortality at 60 days but we will also study a number of other outcomes that are important to patients.",,-99,McMaster University,2645389.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Clinical trials for disease management,2022 +P26535,450607,An mHealth Intervention and Community Partnership to Promote Mental Health in Children born to Mothers with Depression and Psychosocial Stress during COVID-19: A randomized controlled trial,"An estimated 30% of babies born during the COVID-19 pandemic were exposed to depression in-utero. Maternal depression negatively impacts parenting and increases the risk for child mental health and developmental problems. Risks for children and families are particularly high when maternal depression continues into the toddler years and occurs alongside high levels of stress, which were also heightened during the pandemic for many families. Easy-to-access programs are urgently needed to build resilience in, and prevent mental illness for a generation of children exposed to maternal depression and co-occurring stressors during the pandemic. We will address emerging mental health needs using a new App-based Therapy that was co-developed with parents over the past year. The 10-week BEAM Program ""Building Emotional Awareness and Mental Wellness"" combines best-practices for treating depression alongside emotion-focused parenting content to improve parent-child relationships and enrich children's social and emotional skills. Delivered through cell-phones, by therapists from our community agency partners, BEAM includes anytime access to program content, a community forum with other parents, and weekly group therapy. We expect this work to be successful because our approach has been co-developed and tested with a parent advisory board and community agencies. Discussions with local and national collaborators highlight the value of such accessible programs that support both parent and child mental health. BEAM has high impact potential to prevent mental illness in at-risk children during the COVID-19 pandemic and beyond.",,-99,University of Manitoba,121638.18,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Indirect health impacts",2021 +P26537,499053,"Indigenous Health Counts: Combining Respondent-Driven Sampling, Partnerships and Training to Empower Urban Indigenous Communities","Most First Nations, Inuit and Metis Peoples in Canada live in cities. There is a lack of reliable health information for these First Peoples. For example, reported population sizes are commonly smaller than true counts. The result is large gaps in services and missed opportunities to improve health and well-being. It is important to work together to 'count in' these large, diverse, and often overlooked populations of First Peoples. Our Health Counts projects have been run in partnership with urban Indigenous service providers in six Ontario cities over 15 years. Together we have created the largest source of health and wellness information available for First Peoples living in Canadian cities. To ensure high quality data, we used a new statistical method called respondent-driven sampling. I am a statistician with over 10 years of experience working with Indigenous communities. I have created and implemented new statistical methods to study pressing health priorities for First Peoples living in cities, including diabetes, heart disease and COVID-19. Under the leadership of Indigenous community partners, this research program builds on the Our Health Counts studies. We will develop and refine new statistical methods to: 1) Create the most accurate counts of First Peoples living in cities. This is important as all health and social planning programs require correct population counts to be successful; 2) Measure the long-term impact of the COVID-19 pandemic on chronic conditions and mental health outcomes like diabetes, kidney disease, depression, and anxiety; 3) Create a new Indigenous health data training program to train the next generation of Indigenous health researchers and empower them to tell their own stories. In summary, this program will advance high-quality information for First Peoples living in cites. Working together, we can develop and share important, accurate and timely information that will contribute to enhanced health and well-being.",,-99,"York University (Toronto, Ontario)",851777.48,Human Populations,Other,Unspecified,Urban Population/Setting,Indigenous People | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26538,445967,Nonspecific effects of the Bacillus Calmette-Guerin (BCG) vaccine on mortality and infections,"The bacillus Calmette-Guerin (BCG) vaccine used in tuberculosis prevention may lower mortality in babies and children, and prevent infectious diseases other than tuberculosis. Recent studies have suggested that it may also protect against COVID-19 and prevent mortality from this disease. These recent investigations were limited because they only looked at correlations between having a BCG vaccination program and COVID-19 mortality rates. Studies need to be conducted in populations where there are vaccination, disease and mortality registries, so that we know exactly who was vaccinated, who had the disease and who died. In the Province of Quebec, a BCG vaccination campaign took place between 1949 and the mid-1970s. The vaccine was offered for free to newborns and schoolchildren, and vaccination information is compiled in a registry. The goal of our study is to determine if BCG vaccination in early life is associated with decreased mortality and with risk of infections over the life course. We will study selected bacterial and viral infections, and also infections with SARS-CoV-2, the virus causing COVID-19. The study population consists of 400,000 persons. This is almost all individuals born in Quebec between 1970 and 1974. They are now aged 47 to 51 years old. Data was already obtained from provincial administrative databases until 2014, including BCG vaccination status, sociodemographic factors, and death if applicable. We will obtain data on mortality and on use of health services for infections from provincial databases until 2021. We will compare the rates of mortality and of infections (with bacterial and viral infections and with COVID-19 separately) among persons who received the BCG vaccine and those who did not. There are few places in the world where this type of study can be done. Our unique setting will allow us to answer several important questions on BCG vaccination, helping us understand its effects beyond tuberculosis prevention.",,-99,INRS-Institut Armand-Frappier (Laval),316030.15,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2021 +P26539,448908,Better understanding physical and cognitive impairments and functional limitations in people suffering from long COVID to support the development of adapted interventions,"Of the 1,000,000 Canadians who have been infected by COVID-19, 8 to 15% will continue to experience COVID-19 related symptoms well after 12 weeks. The persistence of such symptoms is now defined as ""long COVID"" syndrome. Current evidence does not provide a clear understanding of the physical and cognitive impairments and functional limitations that persons with long COVID present. The objectives of this project are to describe the physical and cognitive impairments and functional limitations experienced by people with long COVID and compare the evolution over 6 months of people from three separate groups: a group of people with long COVID (long COVID Group), another group of people who contracted COVID-19 but did not experience persistent symptoms (acute COVID Group), and a group of people who did not contract COVID-19 (Control Group). One hundred and twenty adults in each of the three groups will be recruited and will take part in three evaluations within 6 months (baseline and 3 and 6 months after baseline). At baseline, all participants will complete questionnaires on sociodemographics, COVID symptomatology and comorbidity, and self-reported questionnaires on quality of life, functional status, sleep, pain-related disabilities, anxiety, depression, fatigue and cognitive function. Then, physical and cognitive tests will be performed in a laboratory to provide complementary results on impairments and functional limitations. Finally, participants will wear a fitness tracker watch to monitor their activity and sleep for 7 days. The participants will complete the same measures (questionnaires, lab measures, fitness tracker watch) at three and 6 months after baseline evaluations. This project will lead to a better understanding of the impairments/limitations experienced following COVID-19. Hence, these results will allow to identify the interventions needed by the population and ensure these are offered through effective healthcare pathways.",,-99,Université Laval,232851.78,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis | Post acute and long term health consequences,2021 +P26540,498304,Human & mosquito microRNA interactions with arboviruses: systematic discovery & functional roles,"Mosquito-borne arboviruses (arboviruses) are major human pathogens, infecting ~400 million people each year. Many arboviruses, such as chikungunya, Zika and yellow fever, have recently globally expanded. Climate change will further increase arbovirus diseases, because warmer global temperatures will allow virus-carrying mosquitoes to spread to new areas. Thus, arboviruses are urgent public health threats, and the majority lack vaccines or specific treatments. Most pathogenic arboviruses have short RNA genomes encoding ~10 genes. This infectious RNA must infect mosquitoes to successfully infect humans. Intriguingly, while humans become sick but usually recover, mosquitoes remain infected for life, happily feeding and infecting new hosts. We still lack an understanding of how these viruses manage to cycle between these dramatically different organisms. This is particularly true in mosquitoes, where a lack of experimental and computational tools has hindered research. We will tackle this problem by using leveraging new methods we developed in mosquitoes. With these sophisticated tools, we will uncover and compare arbovirus interactions with important mosquito and human small RNAs: microRNAs (miRNAs). miRNAs regulate global cellular processes in both organisms, but the specific miRNAs and processes will be very different in each context. We know miRNAs can interact with RNA viruses to directly help or hurt the virus, or to indirectly manipulate host cells. Yet, how and why mosquito-borne viruses interact with organism-specific miRNAs is largely unexplored. This proposal will uncover miRNA interactions with arboviruses in both humans and mosquitoes. Ultimately, this research will broaden our understanding of how arbovirus infect diverse organisms and cause disease.",,-99,University of Toronto,73558.84,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae,,,,,,,,,Rift Valley Fever | Zika virus disease | Congenital Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Animal and environmental research and research on diseases vectors,Vector biology,2023 +P26541,459252,"Covid-19 Pandemic Concealing a Syndemic of Concern: Sex, Gender, Methamphetamine and Sexually Transmitted and Blood Borne Infections in People Living with HIV in Manitoba","In Manitoba, injection drug use is the most common mode of HIV transmission since 2018. Those who inject drugs are more likely to test positive for HIV, syphilis and Hepatitis C, often at the same time. This is called a ""syndemic"" (many epidemics at the same time). Over the last three years, syphilis infections are rampant in Manitoba. If not found and treated, syphilis can cause devastating infection, including transmission to newborns. In addition to HIV and syphilis there are 11 other infections transmitted by sexual activity or blood products (called STBBI). For some people, a convergence of socio-economic factors, mental health concerns, violence and exploitation, is driving a syndemic of new HIV and other STBBI cases, with disproportionate representation of women who inject drugs. Methamphetamine use is growing in Manitoba and is known to affect access to care and treatment. These determinants of health and disparities are exacerbated by public health measures, as resources for testing and contact tracing for Covid-19, result in decreased capacity to respond to STBBI and distribute harm reduction services. It is unknown how biological sex differences and gender intersect with living conditions including experiences of violence and injection drug use. In this project we will ask: How many people (by sex and gender) living with HIV have other STBBI before and during Covid-19? Who is most at risk of acquiring other STBBI, and why? What are the barriers and gaps that put people at risk for infection and prevented them from getting proper care and treatment before and during Covid-19? And What are the recipes for successful engagement of people living with HIV and who inject methamphetamine that endured during the Covid-19 pandemic? The explicit understanding of women, men and non-binary persons living with HIV who use methamphetamine can identify unique gaps and resilience factors that can inform better, tailored testing and clinical and program responses.",,-99,University of Manitoba,284995.67,Human Populations,Unspecified,Unspecified,Unspecified,Drug users | Sexual and gender minorities | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26543,460253,COVID-19 And Severe Community-Acquired Pneumonia Dynamic Evaluation Study (CASCADES - ARBS CORONA III),"Bacterial community-acquired pneumonia (CAP) is a common complication of chronic heart, kidney, lung diseases and diabetes. During the COVID-19 pandemic (2020-present), changes to health care access could have increased the occurrence and death rate of CAP especially in patients with chronic heart, kidney, lung disease and diabetes. COVID-19 could increase occurrence of CAP because of over-crowding during lockdown, less frequent physician visits and thus inadequate treatment of underlying diseases, and increased alcohol and drug use (both risk factors for CAP). We chose to study effects of COVID-19 on CAP because (1) CAP is similar to COVID-19 (characteristics, treatments, and requirement for hospital and ICU admission) and (2) CAP patients may be disadvantaged during COVID-19 waves (e.g. decreased pneumococcal vaccine use, sub-optimal treatment of CAP and limited ICU bed availability). Because of changes to the frequency of CAP, patient characteristics, adherence to treatment guidelines, treatment, and ICU bed availability, we believe that the death rate of CAP patients increased during COVID-19 compared to pre-COVID-19 (2018-2019). To understand how COVID-19 has impacted CAP mortality, we will compare the number of CAP cases during the pre-COVID-19 period and during COVID-19 in sites across Canada. We will analyze the baseline characteristics, treatment, adherence to treatment guidelines to understand what changes occurred and whether these changes increased mortality of CAP. This study is a natural extension of our well established and funded ARBs CORONA program with experts in epidemiology, COVID-19, CAP, sepsis, heart, kidney and lung disease, public health, microbiology, and trials. Our study could drive changes in CAP management:(1) increased pneumococcal and H. influenza vaccine programs, (2) enhanced earlier CAP diagnosis, (3) CAP screening protocols in emergency departments, and (4) greater adherence to CAP treatment guidelines.",,-99,University of British Columbia,402976.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26544,486241,"Sex differences of COVID-19 serological response of individuals infected, vaccinated, or those with hybrid immunity in Ontario.","Differences in COVID-19 infections were well known to vary by sex early in the COVID-19 pandemic; older males with comorbid conditions were experiencing more severe outcomes compared to females. As individuals continue to get infected with the COVID-19 virus, instances of long COVID syndrome are becoming more common and in contrast, more so in females. A preliminary report by Statistics Canada and the Public Health Agency of Canada found that 18% of female adults who tested positive or had a suspected COVID-19 infection reported developing the syndrome. These sex differences are known to be driven by well known discrepancies in immunologic response. However, sex differences in long-term immunity have not been re-evaluated since the introduction of mass vaccination programs. As such, this study will evaluate the long-term effectiveness of vaccine immunity and infection-acquired immunity by assessing the association of long-term immune protection by sex from 2021-2022 in Ontario. Data for this project has already been collected via the COVID-19 Immunity Task Force, including serology data from the Canadian Blood Services and de-identified sex information from the Ontario Registered Persons Database. The serology information comes from donated blood samples that were randomly tested for COVID-19 antibodies. Based on the results, samples were classed as infected with SARS-CoV-2 or as vaccinated. Our analyses will evaluate the association between sex and antibody response. Data from individuals who have donated multiple times and show hybrid immunity, an instance of viral infection and another instance of vaccine antibodies (or vice-versa), will also be included. This study will provide additional insights regarding long-term vaccine effectivity and COVID-19 immunity by sex.",,-99,McGill University,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +P26548,450260,Enhancing vaccine development via comprehensive evaluation of humoral immunity: COVID-19 as a paradigm,"As of July 2021, four COVID-19 vaccines are available in Canada. Approval of new vaccines will require a better understanding of how COVID-19 vaccines work and protect against infection. Our overall objective is to compare (i) antibody responses to these 4 COVID-19 vaccines and (ii) peoples' immune responses after vaccination or natural infection by the SARS-CoV-2 virus. Natural infection is usually considered the 'best' immune response to protect against future infection. We will recruit child and adult volunteers in two groups: those who were vaccinated (total 400 people) and those who had COVID-19 (total 158 people). For those who were vaccinated, we will collect blood samples in before and after vaccination. In those who were infected, we will collect samples up to 12 months after infection. We will also collect information to see if there are other factors (eg, age, sex, gender, other health issues) that affect the person's responses. We will measure responses after vaccination and infection by analysis of how much antibody there is and what the antibody is doing, and of changes in genes that are switched 'on' or 'off'. To analyze the data, we will use sophisticated methods we developed and used to understand how hepatitis B virus vaccines work. We predict to be able to identify similarities and differences, at a molecular level, in immune responses among the different vaccines and between vaccination and natural infection. These head-to-head comparisons will help us to make more effective vaccines in Canada and around the world.",,-99,University of British Columbia,324368.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P26550,468880,Harnessing mobility data to inform public health decision making,"Smartphones have become an essential part of our daily lives. Globally it is estimated there are 6.6 billion smartphone users and by 2026 this is expected to increase to 7.5 billion. The unprecedented number of people with access to smartphones has created an opportunity to amass and track population-level mobility patterns through Global Positioning Systems (GPS). When smartphone users download certain application (i.e. weather, navigation or social media) they allow the applications to track and record their locations. The magnitude and value of these analytics are not lost by commercial companies who buy these data, mostly for targeted advertising purposes. The COVID-19 pandemic exposed the capacity of using mobility data as an epidemiological surveillance tool to support public health decision-making. Here we propose expanding on our mobility research which uses aggregated location data collected by smartphones via GPS as a means to evaluate adherence to policies, and identify disparities and the impact of the COVID-19 pandemic at long-term care facilities and hospitals. We have put together a team that brings together expertise in epidemiology, biostatistics, geriatrics, and geospatial analytics using big data to provide new insights on how to optimally leverage anonymous mobility data that can continue to inform public health decision making post-pandemic.",,-99,"Queen's University (Kingston, Ontario)",78410.34,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2022 +P26551,450300,Non-human primate depletion models for the study of Lassa virus pathogenesis and correlates of protection associated with Lassa fever vaccines.,"Lassa virus is a prominent cause of severe hemorrhagic disease in humans, referred to as Lassa fever, primarily in West African countries. In nature, Lassa virus uses a common rodent species as its natural reservoir and is transmitted directly from infected rodent to human, though human-to-human transmission also occurs. It is estimated that greater than 300,000 people are infected each year with Lassa virus resulting in significant illness and death across this region of Africa. Despite this, no vaccine is currently approved for use to prevent illness in humans. The methods utilized by Lassa virus to cause disease are largely unknown, though it is thought that excessive immune responses in humans plays a vital role in the severity of disease. To explore this, we seek to impair certain cell types responsible for defined immune responses in an animal model of Lassa Fever to clarify their roles in disease progression and severity. A better understanding of both beneficial as well as harmful immune responses will aid scientists in developing targeted medicines to treat Lassa Fever in humans. Expanding on these findings and using a similar immune dampening approach, we then aim to demonstrate that immunization with a leading made-in-Canada Lassa Fever vaccine results in protection from LASV infection through the generation of a potent antibody response.",,-99,Public Health Agency of Canada (Winnipeg),324368.49,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P26552,489200,How do flaviviruses orchestrate viral RNA replication and virion assembly?,"Flaviviruses, including Zika virus and Dengue virus, are mosquito-borne pathogens of public health concern, with more than 2.2 billion people at risk of infection. While many cases remain asymptomatic, symptomatic infections lead to rash, fever, arthralgia, myalgia, headache, retro-orbital pain, and conjunctivitis. More serious complications include hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, congenital abnormalities, and fetal death. Despite decades of research, our understanding of the fundamental biology of flaviviruses, including how they replicate their genomes and build viral particles, remains rudimentary. Today, the technologies exist to allow us to tease apart the roles of the main viral proteins in mediating these processes. Herein, we are studying two viral proteins known to participate in both the process of viral genome replication and viral particle assembly, and are therefore highly lucrative targets for antiviral intervention. Insight into these processes, and how the viral proteins interact with one another and with the viral genome, will allow us to develop novel antiviral strategies and design new vaccination approaches for these important human pathogens. Moreover, given the conservation of these viral proteins across the flavivirus genus, our results are likely to be applicable to several other important human pathogens.",,-99,University of British Columbia,754051.64,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P26555,447801,Advancing virtual care in stroke rehabilitation: A randomized controlled trial investigating the TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL) program,"Leg weakness is very common after stroke. It affects the ability to walk and balance among people who have had a stroke. The first year after stroke is an important time for rehabilitation because it is the best time for recovery. Unfortunately, many people who have had a stroke often feel that they do not receive enough rehabilitation to restore their ability to use their legs. This is especially true for people who live in smaller communities where there are few health services, and more recently due to the COVID-19 pandemic where physical distancing between patients and clinicians has limited the amount of in-person rehabilitation. It is therefore important to develop innovative leg rehabilitation programs that are both cost effective and accessible. Our team of stroke survivors, clinicians and research scientists from across Canada has recently developed TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL). TRAIL is a 4-week program that focuses on exercise to improve leg function. It is delivered using the Internet and computer/tablet by a physical therapist. In this study, we will examine if TRAIL improves walking, balance, leg strength, and quality of life to a greater extent than a 4-week education program (EDUCATION), that focuses on providing education on stroke risk factors for secondary prevention. Ninety-six volunteers who have had a stroke in the past year will be randomly assigned to participate in either TRAIL or EDUCATION. Volunteers will be asked to complete assessments and questionnaires before and after the programs, and again 2 and 5 months later. Assessments will be conducted using videoconferencing so that volunteers will not need to travel to a hospital to participate in the study. We are working with 6 cities across Canada (Halifax, Toronto, London, Winnipeg, Vancouver, Kelowna). We anticipate that TRAIL is an accessible program that will help improve leg recovery after stroke.",,-99,University of British Columbia,59583.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26556,444017,Advancing virtual care in stroke rehabilitation: A randomized controlled trial investigating the TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL) program,"Leg weakness is very common after stroke. It affects the ability to walk and balance among people who have had a stroke. The first year after stroke is an important time for rehabilitation because it is the best time for recovery. Unfortunately, many people who have had a stroke often feel that they do not receive enough rehabilitation to restore their ability to use their legs. This is especially true for people who live in smaller communities where there are few health services, and more recently due to the COVID-19 pandemic where physical distancing between patients and clinicians has limited the amount of in-person rehabilitation. It is therefore important to develop innovative leg rehabilitation programs that are both cost effective and accessible. Our team of stroke survivors, clinicians and research scientists from across Canada has recently developed TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL). TRAIL is a 4-week program that focuses on exercise to improve leg function. It is delivered using the Internet and computer/tablet by a physical therapist. In this study, we will examine if TRAIL improves walking, balance, leg strength, and quality of life to a greater extent than a 4-week education program (EDUCATION), that focuses on providing education on stroke risk factors for secondary prevention. Ninety-six volunteers who have had a stroke in the past year will be randomly assigned to participate in either TRAIL or EDUCATION. Volunteers will be asked to complete assessments and questionnaires before and after the programs, and again 2 and 5 months later. Assessments will be conducted using videoconferencing so that volunteers will not need to travel to a hospital to participate in the study. We are working with 6 cities across Canada (Halifax, Toronto, London, Winnipeg, Vancouver, Kelowna). We anticipate that TRAIL is an accessible program that will help improve leg recovery after stroke.",,-99,University of British Columbia,221828.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26557,438171,Advancing virtual care in stroke rehabilitation: TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL),"Leg weakness is very common after stroke. It affects the ability to walk and balance among people who have had a stroke. The first year after stroke is an important time for rehabilitation because it is the best time for recovery. Unfortunately, many people who have had a stroke often feel that they do not receive enough rehabilitation to restore their ability to use their legs. This is especially true for people who live in smaller communities where there are few health services, and more recently due to the COVID-19 pandemic where physical distancing between patients and clinicians has limited the amount of in-person rehabilitation. It is therefore important to develop innovative leg rehabilitation programs that are both cost-effective and accessible. Our team of stroke survivors, clinicians and research scientists from across Canada has recently developed TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL). TRAIL is a 4-week program that focuses on exercise to improve leg function. It is delivered using the Internet and computer/tablet by a physical therapist. In this study, we will examine if TRAIL improves walking, balance, leg strength, and quality of life to a greater extent than a 4-week lifestyle coaching program (LIFESTYLE), that focuses on improving physical activity, diet, and stress management. Ninety-two volunteers who have had a stroke in the past year will be randomly assigned to participate in either TRAIL or LIFESTYLE. Volunteers will be asked to complete assessments and questionnaires before and after the programs. Assessments will be conducted using videoconferencing so that volunteers will not need to travel to a hospital to participate in the study. We are working with 5 cities across Canada (Halifax, Toronto, London, Winnipeg, Vancouver). We anticipate that TRAIL is an accessible program that will help improve leg function within the important early window of recovery after stroke.",,-99,University of British Columbia,74711.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26559,485666,"Mobilizing outputs from INPUT: The Information Needs, Perspectives and Uncertainties of COVID-19 Project. Co-creating opportunities for shared dialogue to address knowledge and information needs within the context of racialized communities prioritized for COVID-19 vaccination.","The Information Needs, Perspectives, and Uncertainties on COVID-19 Vaccinations (INPUT) project has worked closely with community partners, especially within the Historic African Nova Scotian (ANS)communities of the Preston Township, to explore concerns about COVID-19 vaccines, discover what information and sources of information are valued in decision-making, and how knowledge is best shared based on values, beliefs and culture. Through our partnership and work on the INPUT project, it has become clear that there are many unanswered questions and concerns about COVID-19 vaccines and vaccination, most notably around the policy decision-making that prompted the prioritization of the ANS community. In keeping with the values expressed by our community partners, we propose the co-creation of a series of evenings of conversation between valued experts and community members where knowledge can be exchanged and new insights formed for all participants around the issues and concerns arising from the work of the INPUT study.",,-99,Dalhousie University (Nova Scotia),5823.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2023 +P26560,463078,The Youth Development Instrument: engaging stakeholders and linking data to monitor and promote youth mental health and well-being trajectories beyond the pandemic,"Mental disorders have a peak onset in adolescence and young adulthood, with 1 in 5 Canadians under the age of 25 affected per year. Along with social and economic stressors such as discrimination and income inequality, youth face unique impacts caused by the climate crisis and the COVID-19 pandemic. Social and emotional learning and positive childhood experiences can avert or delay mental illness onset and/or severity, yet 95% of health system funding is allocated to specialized, hospital-based or downstream services. Through intersectoral collaborations, we developed the Youth Development Instrument (YDI) to measure youth mental health (MH) and well-being and to investigate how childhood experiences influence MH and well-being trajectories in emerging adulthood. Developed to measure MH and well-being of Grade 11 students, the YDI was first piloted in Spring 2021. Wave 1 collected ~2,300 responses in 6 school districts in British Columbia (BC). By the end of Wave 2 (Spring 2022), we anticipate collecting 10,000 responses from 22 BC districts. Our project aims to: 1) Monitor pandemic-era youth MH and well-being using the YDI; 2) Identify early life risk and protective factors of internalizing and externalizing MH outcomes and life satisfaction in youth in the context of the COVID-19 pandemic; and 3) Inform the development of a collaborative data-to-action strategy to support school, community, and health system stakeholders in improving youth MH and well-being during COVID-19 recovery using Aim 1 and 2 findings. Mental disorders pose a critical threat to young people's current and future health. Early intervention may prevent a substantial portion of this burden but requires an understanding of the complex web of its determinants. We will link the YDI to other data sources to create a comprehensive map of the links between child and youth development and MH in emerging adulthood, in turn informing data-to-action initiatives.",,-99,"Simon Fraser University (Burnaby, B.C.)",432471.9,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26561,475418,The Youth Development Instrument (YDI) Ambassador Project: A youth participatory action research initiative,"With the goal to amplify youth participation in every stage of the research process, this project aims to create a Youth Ambassador program, which includes a youth participatory action research study (YPAR), a summer research institute and wellness retreat, and employment opportunities for youth as research assistants and knowledge translation ambassadors. Youth will use data from the Youth Development Instrument (YDI), a self-report survey for adolescents ages 15 to 18 that measures individual and contextual youth well-being and resilience indicators are measured in five dimensions: social and emotional development, social well-being, learning environment and engagement, physical and mental well-being, and navigating the world. Since 2020, the YDI has collected data from 11,500 students across 22 school districts in British Columbia, with another estimated 15,000 in 30 school districts and 25 independent schools to participate in the 2022-2023 school year. This project will yield youth-identified research priorities for health and well-being that they themselves can bring to youth-focused organizations, such as schools, community organizations, health-care services, parent advisory committees. This project is of great relevance given that Canadian youth report some of the lowest levels of well-being worldwide. Youth ages 15 to 24 experience disproportionate levels of mental distress compared to other population age groups in Canada and adverse mental health trends have worsened since the onset of COVID-19. Our Principal Knowledge User, Frayme, is an international organization that provides youth health and social supports to youth connecting them with more than 400 service providers across 12 countries. Frayme will help disseminate YPAR findings and knowledge translation materials to its 370 network partners to ensure YPAR findings that provide youth perspectives on their own well-being inform agencies and policy designed to support them.",,-99,"Simon Fraser University (Burnaby, B.C.)",66805.66,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26563,448863,Predictors and burden of post-acute COVID-19 syndrome (long-COVID) with a focus on equity,"Post-acute COVID-19 syndrome (long-COVID) is a complex condition where patients experience persistent symptoms after recovering from their initial illness. Long-COVID can be mild to severe and involve a range of physical, cognitive, and psychological symptoms. Evidence on long-COVID scarce; the incidence, natural history, risk factors for long-COVID, and burden of disease - in terms of health outcomes, resource use, and cost - are currently unknown. We propose to conduct a population-based matched cohort study in Ontario and British Columbia to characterise the burden of long-COVID through an equity lens. We will use population-based laboratory, reportable disease, immunization, and health administrative databases, enriched by individually-linked detailed clinical data from Canadian patients with long-COVID. We will match patients with long-COVID to patients without long-COVID and the general population to determine the incidence, predictors,and long-term health outcomes, resource and cost of long-COVID. We will stratify our population by demographic (e.g., age, sex), clinical (e.g., severity of acute COVID episode, comorbidities, vaccination status, variant of concern), and social and equity-relevant variables (e.g., gender, marginalization, essential workers, multigenerational and large households, congregate settings). Our work will significantly enhance the understanding of long-COVID and inform the value of potential interventions and hence will directly support clinical and health policy decision-making aimed at reducing the impact of long-COVID on Canadians.",,-99,Toronto General Research Institute,396940.38,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Post acute and long term health consequences | Indirect health impacts,2021 +P26564,485898,Long-term impacts of COVID-19 on youth and adolescent mental health.,"Long-term impacts of COVID-19 on youth and adolescent mental health.Background: There is much heterogeneity in evidence that exists about mental health during the COVID-19 pandemic. Most evidence focussing on youth and adolescents, though, seem to indicate a worsening of mental health, such increasing anxiety and depression symptoms. All existing longitudinal evidence regarding mental health during COVID-19 use pre-pandemic measures as a baseline, then measures taken during early stages of the pandemic, so long term mental health effects post-pandemic are still unknown. Some literature from previous global disasters suggests poor mental health can be sustained in a youth population for long periods of time, though things such as increased resiliency in youth may create more long-term stability. Objectives: This study aims to clarify the longer-term effects of COVID-19 on Canadian youth and adolescent mental health. Proposed Methods: Longitudinal data will be derived from iterations of the Canadian Community Health Survey (CCHS). Mental health outcomes, such as depression, anxiety and self-perceived mental health will be compared over several years to determine trends. Significance: COVID-19 was an unprecedented worldwide health event that has unknown long-term impacts on the population. Beyond continuing to document the effects of this pandemic and associated control measures on mental health, it is important to understand the impacts on youth and adolescent populations, as potentially the most vulnerable, yet most resilient age group with regards to mental health.",,-99,University of Calgary,13021.09,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26567,459232,Adverse Effects of SARS-CoV-2 Vaccines in Kidney Transplant Recipients,"The COVID-19 pandemic has presented an unprecedented challenge to Canada. To date, >1.5 million Canadians have been infected with the SARS-CoV-2 virus, and >27,000 individuals have died. The impact is even greater in kidney transplant recipients (KTR), often including members of ethnocultural, Indigenous, marginalized communities, with incidence exceeding that of the general population by 15-fold, and risk of death also higher. Differences between KTR and the general population have been attributed to immunosuppression geared towards attenuating the immune response and thus prevent rejection. The immunosuppressed state contributes to markedly lower neutralizing antibody responses to SARS-CoV-2 vaccines in KTR, which may still be offering protection; however, vaccine-induced anti-HLA antibody development, may increase risk of graft rejection and loss. Immune response to vaccines, viruses, and donor specific proteins (HLA) by KTRs' sex and age, with young females generating greater innate and adaptive immune responses than males. Our study will utilize longitudinally collected biospecimens from the MUHC Kidney Disease Biorepository. We will ascertain donor and recipient HLA genotypes by next generation sequencing, and anti-HLA antibodies - by solid phase assays. Using high-resolution genomic technologies, we will study the molecular makeup of blood immune cells and their activity. Simultaneous profiling of variation in genomic sequence of receptors on immune cells will allow us to identify expansion of antibody forming cells and their relative distribution before and after vaccination. We will evaluate desirable as well as undesirable antibody responses to mRNA SARS-CoV-2 vaccines and how they are modified by timing, dose, and vaccine product, as well as KTRs' age and sex. This work will offer solutions towards the prevention of SARS-CoV-2 infection and decrease risk of graft rejection through personalized management of vulnerable KTR.",,-99,Research Institute of the McGill University Health Centre,394170.93,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P26569,475192,Workforce planning for inpatient medical and intensive care physician services to support health system planning and pandemic resilience,"The Covid-19 pandemic has exacerbated long-standing challenges in staffing for emergency health services. The proposed project aims to develop new methods to quantify the mismatch between demand and supply for physician emergency health services to support Health Human Resource (HHR) planning. We will focus on adult inpatient medicine and intensive care physicians to develop, refine, and validate our approach, because inpatient medical services care for the largest group of hospital inpatients and the vast majority of Covid-19 hospital patients. We will adopt a patient-oriented approach to generate insights and create tools to allow policymakers to evaluate their options based on projected impacts on various metrics including cost, quality of care, and equity at different time points. Once developed, these methods could be extended to HHR planning for other groups of physicians or healthcare professionals, including nurses.",,-99,University of Toronto,109655.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health service delivery | Health workforce,2022 +P26570,498993,Beyond Disparities: Indigenous Wellness Through Health Research,"This research initiative promotes Indigenous health in Saskatchewan and Canada. The program uniquely integrates Indigenous knowledge, community-based strategies, and health theories to address historical injustice-related health disparities. This program promotes cultural responsiveness with Indigenous communities to bridge Western and Indigenous paradigms. Cultural differences are respected in inclusive healthcare interventions and policies to promote reconciliation. The Indigenous Cultural Responsiveness Framework (CRF) was developed with 74 First Nations communities as the foundation. With historical context and community assets, this paradigm promotes holistic wellness. This application explains Indigenous health using social determinants, intersectionality, and two-eyed seeing. The research program empowers communities, integrates Indigenous knowledge, addresses health disparities, develops innovative treatments, and heals historical trauma. The PI has twelve years of collaboration and engagement and uses Indigenous, quantitative, qualitative, and Participatory Action Research-based approaches to meet community needs, ensuring culturally and contextually relevant interventions boosting research impact. Partnerships with Indigenous organizations, and academic institutions support community-led health promotion programs for chronic diseases, mental health, maternal care, traditional medicines, and COVID-19 response. The Knowledge Mobilization Plan applies research to policies, practices, and community initiatives for real-world impact. The strategy uses social media, webinars, digital channels, community approaches and community engagement. Individual studies emphasize cultural awareness, community involvement, and peer support. The program aims to empower Indigenous communities, reduce health disparities, and promote sustainable change. Policies, practices, and the next generation of Indigenous health leaders are influenced, making healthcare more equitable.",,-99,University of Regina (Saskatchewan),851777.48,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement,2023 +P26572,486136,Assessing the relationship between income inequality and obesity among adolescents during the COVID-19 pandemic,"The prevalence of childhood obesity has likely increased in Canada as a result of the COVID-19 pandemic, as significant increases in body weight and BMI during lockdown periods among school-aged children and adolescents have been found. Childhood obesity is a growing public health concern in Canada, as it contributes to the early development of conditions like type 2 diabetes and cardiovascular disease, resulting in significant resource strains on the Canadian health care system. While the causes of childhood obesity are multifactorial, there is an understanding that the social environment plays an important role in the development of obesity. Income inequality, or the unequal gap between rich and poor, is a social determinant of population health that is associated with increased rates of obesity in developed countries. Possible mechanisms through which income inequality may influence childhood obesity include the exacerbation of mental health conditions, like depression, and/or the weakening of social cohesion, both of which are risk factors for obesity. This research seeks to determine if income inequality is a risk factor for increased odds of obesity among Canadian adolescents during the COVID-19 pandemic. Additionally, it will determine if the association is mediated by mental health conditions and social cohesion. Findings from this research will help identify the relationship between income inequality and adolescent obesity during the pandemic, which in turn, can be used to guide policy and intervention decisions regarding childhood obesity in Canada.",,-99,University of Alberta,13021.09,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P26578,462230,The test-negative design for the estimation of COVID-19 vaccine effectiveness: design evaluation and development of statistical methods in the evolving context,"Fast research designs have been proposed for estimating how well different vaccines protect against disease, severe disease, hospitalization, and death from COVID-19. In fact, ongoing study is needed to evaluate different levels of vaccination (2 doses, boosters, different lags between doses, etc) in terms of how well they protect against illness, which may vary depending on the current circulation of virus variants. These fast designs typically involve identifying people who have been tested for COVID-19, often at a test-site or in a hospital. An established design is called the ""test-negative design"" which specifically involves identifying people who have symptoms associated with the disease in question and who then get tested. Scientists can estimate vaccine effectiveness by comparing people who test positive to people who test negative. If the negatives have higher rates of vaccination, this will indicate effectiveness of the vaccine. But, depending on how the design and statistical methods are applied, there may be bias in the estimation of effectiveness. Our research team has recently noted that, because of challenges of how test data are collected in our healthcare systems across Canada, the classical version of the test-negative design cannot always be applied. For example, some designs have used all test data, rather than only data from those who have certain symptoms. We are interested in evaluating how much bias can be caused by this difference in design, and identifying scenarios in which this can create misleading results. Secondly, we are interested in developing statistical methods that can address the limitations of the regression approach that is essentially the only one currently being used. We will identify limitations of current methods and propose new (or adapted) methods that can address these limitations. Our goal is to produce more reliable statistical methods so that we can improve our monitoring of the benefits of vaccination.",,-99,Université de Montréal,214745.05,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Vaccines research, development and implementation",Impact/ effectiveness of control measures | Characterisation of vaccine-induced immunity,2022 +P26579,486148,Micro triage decisions and moral distress during the COVID - 19 pandemic in critical care providers: A cross-provincial case study,"Moral distress in the workplace is thought to be a driving force behind the burnout and workforce attrition that plagued health care providers (HCPs) during COVID-19. Moral distress occurs when a HCP knows the morally right course of action, but is unable to act upon this due to an institutional constraint. For example, a HCP tasked with determining the allocation of scarce, life-saving medication amongst several patients might experience the effects of moral distress. The HCP would want each patient to have equal access to receive medical treatment, but under the constraints of resource scarcity, this would not be possible. In response to the many challenges brought about by the COVID-19 pandemic, the medical community in Canada devoted considerable attention to the possibility of triaging access to ventilators and other necessary medical attention. However, in most places, these triage decisions with life-endangering consequences did not transpire. Instead, insufficient resources and infection control policies rendered HCPs in the difficult position of having to make an array of small-scale triage decisions. For example, when personal protective equipment was scarce, HCPs had to decide when to enter patient rooms and when to communicate remotely, extend time between doses, or deviate from the standard of care. Collectively, the aforementioned challenges are examples of the ethical decisions which we have termed micro-triage. We posit that the accumulation of micro-triage decisions may manifest as moral distress. In this research project, we will document the routine ethical decisions that HCPs faced during the pandemic, with the objective of developing educational strategies that will serve to better prepare HCPs to make micro-triage decisions in the future.",,-99,McMaster University,13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel | Nurses and Nursing Staff | Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues in Clinical and Health System Decision-Making | Research to inform ethical issues in the Allocation of Resources | Indirect health impacts,2022 +P26582,448941,The School SPIT study (Saliva to Promote Improved Testing): A Stepped-wedge Cluster Randomized Controlled Trial of Take-home Saliva to Promote Symptomatic Testing,"In-person schooling is important for the overall health and wellbeing of children and youth and as a result, enhanced health and safety measures have been put into place in schools to support their return. Of critical importance is the ability to identify cases so that contacts can be identified, appropriately isolated and tested to prevent further transmission. Unfortunately, public health investigations continue to identify students who attended school while symptomatic, so we know that children may not always seek testing, preventing contact tracing from occurring. This may be related to the fact that children can have mild symptoms, may not seek testing due to concerns about the tolerance of testing using a nasopharyngeal swab, and/or parents may have challenges with accessing a testing center. Therefore, reducing barriers to testing by providing take-home saliva kits through the school is likely to improve testing uptake and increase case identification, leading to earlier contact tracing and reduced transmission. In the proposed study, we will evaluate whether the availability of take-home saliva testing kits at schools to improves SARS-CoV-2 case identification. Elementary and high schools situated in both lower incidence regions (west Toronto) and higher incidence regions (Scarborough) will be included and will transition from standard of care (testing at an assessment center) to the intervention (additional availability of take-home saliva kits at school) each week for a duration of 6 weeks. We will compare the rate of case detection in the control period to the intervention period. Active and early diagnosis of individuals with COVID-19 is critical role in reducing transmission. This study will provide important information on whether the availability of a take-home saliva kit for symptomatic students improves equity of access, testing uptake and case identification in schools, which may also be applicable to other congregate settings.",,-99,Hospital for Sick Children (Toronto),242305.67,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Other,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Diagnostics | Impact/ effectiveness of control measures | Clinical trials for disease management,2021 +P26583,490587,"Viral Dynamics of Influenza, RSV and SARS-CoV-2 in Children and Secondary Transmission within Households and Schools","Viral respiratory tract infections are very common in children. They contribute to missed time in school, work disruption for caregivers and can also cause severe illness requiring hospitalization and rarely death. In the 2022-2023, influenza, RSV and SARS-CoV-2 viruses infected a large number of children which strained the pediatric healthcare system in many jurisdictions. Unfortunately, there continues to be limited data on duration of infectiousness and transmission risk of these viruses to inform public health decisions during times when there is significant circulation of these viruses. In the proposed study, we will assess the infectiousness of children with influenza, RSV and SARS-CoV-2 in children by examining the viral load changes over the course of illness to inform return to school (and other activities) guidance. Furthermore, determining which household and school contacts develop infection is important to understand factors that may contribute to transmission. These results will contribute essential data to help: 1) prevent spread in households and schools through refinement of case management and health and safety measures, 2) develop protocols around contact management in households and classrooms, and 3) inform policy decisions in the event of future pandemics with related viruses.",,-99,Hospital for Sick Children (Toronto),818765.77,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Clinical characterisation and management | Infection prevention and control,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis | Restriction measures to prevent secondary transmission in communities,2023 +P26584,486160,Evaluating the Impact of Laboratory Testing on Clinical Outcomes of COVID-19 Patients: A GENCOV Study,"Understanding why patients respond to SARS-CoV-2 infections so diversely has remained an ongoing question throughout the COVID-19 global pandemic. Laboratory testing offers one valuable approach that physicians can use to monitor disease progression and its severity. By measuring various biochemical markers from the blood and other bodily fluids, more can be learned about a patient's physiological condition and how to better treat them. Previous studies show that certain biochemical results, like high troponin and C-reactive protein levels, can be insightful for predicting poor patient outcomes; however, the relation between specific biomarkers and their impact on COVID-19 patient responses is still largely unknown. Moreover, testing utility in terms of test type and frequency of testing is another aspect inherent to monitoring patient responses that has yet to be defined with respect to COVID-19. As such, the proposed project intends to first examine if there is any association between four possible COVID-19 patient outcomes (including intubation, length of hospital stay, readmission, or mortality) and test results of biochemical markers as ordered by physicians. In addition, this project also aims to identify if the frequency of testing has any secondary influence over those same patient outcomes. Evidence from this study will be significant for predicting why some patients infected with SARS-CoV-2 might respond more favorably than others, offering a better understanding of possible illness trajectories. Furthermore, linking biochemical markers and clinical laboratory ordering practices to COVID-19 patient outcomes will have substantial value for informing physicians in how to effectively manage and treat COVID-19 patients in the future.",,-99,University of Toronto,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P26587,486994,Designing Infectious Disease Data Submission Tool Based on User Feedback,"SeroTracker, an evidence synthesis hub housed at the Centre for Health Informatics that tracks COVID-19 antibody prevalence (seroprevalence), aims to expand its surveillance capacity to create a standardized submission template where investigators can directly submit their granular, individual-level data, thus promoting timely, open-access, and collaborative health informatics. To engineer the submission tool, SeroTracker will conduct user interviews to gain crucial feedback from collaborators that would be utilizing this data, including public health agencies and public policy decision makers. Through user interviews this research will inform the building of a new submission tool. The specific objectives are to understand the challenges of infectious disease stakeholders' during the COVID-19 pandemic and to advise on the creation of a health informatics seroprevalence submission tool via SeroTracker.com, incorporating the needs of health data users into its design. Using the Braun and Clarke approach, we will conduct a thematic analysis of user interview responses. Questions will surround stakeholder needs within evidence synthesis and data infrastructure. Coding will be facilitated by Nvivo software before being reviewed and verified by a second coder. Theme generation will be discussed iteratively. Incorporating user-centric perspectives of infectious disease decision makers will lead to tool development which has extremely high potential yield to public health, and leverages investments into serosurveillance.",,-99,University of Calgary,4405.32,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,Epidemiological studies,,2023 +P26589,480709,Reflection Room: Addressing Grief in a Hospice Setting,"The Saint Elizabeth Foundation is a national registered charity, working to strengthen community health care through innovative models, partnerships, and leading practices - with a specific focus on aging and older adults and end-of-life (EOL) care. Our proposed project is to mobilize knowledge within hospice care across Canada by facilitating opportunities to install Reflection Rooms that support grief work for aging and older adults involved with hospice care. Reflection Rooms are evidence-based, participatory art installations that support people to talk about dying, death, and grief by providing an immersive space for visitors to read stories written by others and write and share their own stories. The Saint Elizabeth Foundation, in partnership with the Canadian Hospice Palliative Care Association, will equip hospices across Canada (n=150) with kits which will allow for the installation of Reflections Rooms that my support grief work and provide support for mental health and well-being for aging Canadians involved in hopsice care. The rationale for the proposed project comes from the urgent need for more community-based grief supports particularly in the wake of COVID-19. Many aging Canadians feel lost and alone during bereavement. Grief support is needed in hospices across Canada to allow those using services and working in the setting to have a quiet space to rest and reflect, disclose emotions, and feel connected to others through sharing stories. Over the last two years the Saint Elizabeth Foundation supported the Reflection Room research project run by the SE Research Centre that investigated how Reflection Rooms increase comfort talking about dying and death in community and health care settions (e.g., hospicies) and how the address pandemic-related grief in long-term care homes in Ontario.",,-99,"Saint Elizabeth Health Care (Markham, Ontario)",7385.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26591,495949,A Narrative Inquiry into the Experiences of Children and Youth Waiting for Mental Health,"The mental health of children and youth in Canada has been greatly impacted by the COVID-19 pandemic. The COVID-19 pandemic worsens existing mental health symptoms among children and youth as well as leads to new mental health issues due to prolonged isolation, illness in the home, fear of infection, school closure, familial financial loss, disruption of routine, and uncertainty of the future. Children and youth may also be affected by exposure to domestic violence, child maltreatment, lack of free school meals, decreased access to social and academic school supports, housing and overcrowding concerns, and a significant change to social networks. Public health restrictions have erased access and involvement with community activities and adult supports outside of the home that often serve as protective factors and help young people to cope with mental health issues. Unfortunately, COVID-19 has worsened the urgent need for child and youth mental health services that already existed in Canada before the pandemic. The results of ""waiting"" for care and treatment can be devastating resulting in early school leaving, unemployment, involvement with the youth justice system, bullying, trauma, substance use, economic burdens, and suicide. This research study will explore 1) the experiences of children and youth who are waiting for mental health services during the COVID-19 pandemic, 2) identify resources, strategies and supports used by children and youth while they were waiting for mental health services, 3) strengthen current child and youth mental health care system in Canada through providing knowledge of innovative resources, strategies and supports for children and youth that can be utilized to help children/youth cope while they wait for formalized mental health treatment",,-99,MacEwan University (Edmonton),4405.32,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Indirect health impacts,2023 +P26593,459218,COVID-19 in pregnancy - impact on birth and placental outcomes and associations with race.,"COVID-19 in pregnancy is associated with higher rates of hypertensive disorders of pregnancy and preterm birth due to severe maternal symptoms, and the infants of such pregnancies also require neonatal intensive care at a higher rate than non-infected preterm births. Studies also suggest an increase in pregnancy associated hypertension may be driven by race. We have shown that placentas from mothers with COVID-19 are damaged resembling placentas from pregnancies with preeclampsia or preterm birth. But we do not know if this finding is more common in pregnant women who identify as black vs. those who don't. The placenta expresses ACE-2, the protein that SARs-CoV-2 uses to infect cells. ACE-2 is part of a regulatory pathway - the Renin-Angiotensin System or RAS, which controls blood pressure. We have shown that placental levels of ACE-2 are lower in Black women. We think that this might make these women more likely to get hypertensive complications of pregnancy. We have brought together a group of experts from Canada and the USA with expertise in viral infection in pregnancy, placental pathology, and babies health. We have collected many placentas and samples from mothers with COVID-19 in pregnancy. We will examine if race makes pregnancies more vulnerable to serious COVID-19 complications and increases the risk for placental damage. We will explore associations between race and the RAS system in the placenta, and pregnancy and birth outcomes in women with COVID-19 infection in pregnancy. This research will identify the mechanisms behind the differential rise in pregnancy complications and placental damage associated with socioeconomic status and race in the COVID-19 pandemic.",,-99,University Health Network (Toronto),197146.98,Human Populations,Black | Other,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Post acute and long term health consequences,2021 +P26605,448817,Gathering stories to inform culturally safe community strategies (CSCS) to improve trust in public health measures (PHM) in Indigenous peoples (IP) in Northwest Territories (NT),"This project will gather stories and experiences of Northwest Territories (NT) Indigenous peoples (IP; men, women, and non-binary) with COVID-19 (C19) public health measures (PHM) and confidence in following PHM to provide culturally relevant, safe, and gender specific suggestions for increasing utilization of C19 PHM. The team is well-positioned to effectively and quickly collect these data as an extension of a CIHR-funded C19 project, which is co-led by Hotii ts'eeda SPOR Unit in NT, partnered with 10 NT communities, and guided by a Community Advisory Board (CAB), that includes Elders and youth. Using a community based approach and Indigenous methodologies (e.g. storytelling), we will recruit 200 IP for one-on-one open-ended interviews to: 1. Gather stories from IP on experience with PHM and healthcare services and confidence in following PHM (e.g. social gathering restrictions, travel restrictions) and how this differentiates by gender; 2. Identify the barriers to and opportunities for improving confidence in PHM and safety measures; 3. Document recommendations from IP to inform culturally safe community strategies to increase the following of C19 PHM; and 4. Disseminate findings to communities, governments, Indigenous governments and organizations, international Indigenous partners utilizing an Integrated Knowledge Translation approach. We will contribute to local capacity building, employment, and sustainability by hiring community research assistants to recruit and host interviews. Data will be analyzed qualitatively using a narrative approach guided by the CAB. The team is comprised of Indigenous researchers, NT public health policymakers, specialists/experts (qualitative research, C19 pandemic research) and international and national collaborators/advisory board members, and therefore results will be relevant for Indigenous Arctic communities at the community, regional, territorial, national and international levels.",,-99,University of Alberta,396002.94,Human Populations,Other,Unspecified,Unspecified,Indigenous People | Sexual and gender minorities,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2021 +P26606,435552,"Assessing attitudes, barriers, and opportunities for human papillomavirus (HPV) vaccination (HPVV) to inform, develop, implement, and evaluate a culturally appropriate program for increasing utilization and addressing vaccination hesitancy in Arctic Canadian Indigenous communities","Northwest Territories (NT) Indigenous communities have expressed concerns for the number of people affected by cancer. Human papillomavirus (HPV) is a common sexually transmitted infection that can lead to cervical and other types of cancer. HPV vaccination is a safe and effective way to prevent cervical cancer caused by HPV. Yet, NT school-based vaccination rates are among the lowest in Canada for reasons that are not well-known. There is an urgent need for community-specific, culturally-relevant strategies that are appropriate and effective to increase knowledge and willingness for HPV vaccination in the NT. Given the current pandemic, communities have also asked us to address concerns regarding vaccination for when a COVID-19 vaccine is developed. Furthermore, COVID-19 is likely further reducing HPV vaccination coverage and utilization of other cancer screening services in NT. This project will work closely with 2 NT communities using Indigenous methodologies and Two-Eyed Seeing to listen to peoples' experiences and concerns surrounding HPV, HPV vaccination, and vaccine hesitancy within the context of COVID-19. Working collaboratively with community members and healthcare providers, this project will develop, implement and evaluate a culturally safe, community-based program, designed and delivered by local staff, utilizing on-the-land and traditional activities, to understand and address concerns related to cervical cancer, and HPV/COVID-19 vaccine hesitancy; increase HPV vaccination; and ultimately reduce the burden of HPV-related cancers. This project could greatly reduce the burden of cervical and other related cancers by increasing HPV vaccination in remote Arctic Indigenous communities while providing salient knowledge regarding HPV vaccination, as well as community member willingness towards a potential COVID-19 vaccine.",,-99,University of Alberta,1571751.76,Human Populations,Other,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2020 +P26607,488954,Advancing Equity-Focused Implementation Science: A Multiple Case Study of Best Practices for Community Health Workers in Primary Health Care,"Health care has been very strained over the past few years because of the COVID-19 pandemic. This has caused many family doctors to leave their practice, for example, through retirement. Inequities in care, where certain communities face barriers to seeing their primary care provider (e.g., their family doctor), have also gotten worse. In this project we plan to implement better ways of serving communities who face barriers to care by supporting providers called Community Health Workers to provide the best care possible. We will help to train Community Health Workers at 4 health care organizations to better serve their communities. Community health workers are hired from the communities they serve, and they help to coordinate the different parts of care in health and social services (e.g., both the family doctor and newcomer settlement services) and promote the health of people who face barriers to care. We have built a new way of planning and implementing best practices to promote better care for people from communities that face barriers to being healthy. We will test this new approach by implementing better practices in the four organizations, and we will use our results to support a group of policy and health care leaders who want to support Community Health Workers to provide better care that helps to coordinate services around patients' needs. The results of our project will inform research, health care policy, and health care leaders to introduce best practices for Community Health Workers in primary health care.",,-99,Women's College Hospital (Toronto),506452.6,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health workforce,2023 +P26609,451641,To enhance prenatal education program interrupted by COVID-19 in remote and rural First Nations communities by expanding remote education through two-eyed seeing framework to improve maternal child health,"Diabetes in pregnancy is an important risk factor for type 2 diabetes (T2D) in women and their offspring. First Nations (FN) people, especially those living in isolated communities, have a higher risk for diabetes in pregnancy and in youths compared to non-FN population. Our recent study demonstrated that a community-driven remote prenatal education improved participation in prenatal program and breastfeeding in FN women in rural or remote communities, but the outcome was affected by Wi-Fi service and postpartum supports in the communities. COVID-19 disrupted regular prenatal education and care in the communities. However, remote prenatal education remained active in participating communities. We propose to enhance the prenatal program by improving remote prenatal education using two-eyed seeing framework, and the incorporation of community-created educational format to revitalize community prenatal program interrupted by COVID-19 to increase program participation and improve pregnancy outcomes in rural and remote FN communities. Traditional education will be provided by FN Elders or Knowledge Keepers to pregnant women and their partners to promote spousal support and family-centered breastfeeding. The enhancement of prenatal program will help to improve prenatal education and the health and wellness of women and children in rural and remote FN communities. Our team is composed of Indigenous Principal Applicants, Knowledge Users, community partners, collaborators and multidisciplinary researchers with expertise in Indigenous or gender research. The project will be conducted following guidelines for Indigenous health research and the results will be owned, possessed accessed and controlled by community health authorities. The proposed studies will reduce inequity in prenatal education in women and children in remote or rural FN communities. The outcome can be scaled up to other communities to improve the health of Indigenous women and children in Canada.",,-99,University of Manitoba,910937.32,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26610,468147,Mapping the navigation of mental health services: a planning proposal for catalyzing innovation with service navigation through collaborative research,"The COVID-19 pandemic and its public health measures have taken a toll on the mental health of Canadians. However, many barriers exist that prevent Canadians from accessing the mental health supports and services they need. One barrier is the challenge of navigating how and where to receive care. Navigation was identified by Canadians as their top digital mental health priority in a 2021 survey. Navigating the mental health system is complex and not well-understood. In partnership with individuals with lived/living experience, this planning project will start a dialogue on their experiences navigating mental health care services. Through a series of workshops, a journey map of their experiences will be co-created. The map is intended to identify barriers and gaps encountered by those seeking care. The map will also identify enablers that eased the navigation process. Lastly, the map will identify and prioritize opportunities for mental health organizations to innovate and act to support patient navigation. A knowledge mobilization strategy will also be developed in the session. The strategy will outline how to use the journey map and how get it to the right people for immediate action and impact. The journey map, priority areas for innovation, and knowledge mobilization strategy can advance the priorities of the Institute of Neurosciences, Mental Health, and Addiction (INMHA). In particular, the proposed project will catalyze research opportunities in mental health areas of emerging need. The journey map and priority areas for innovation can be used as a framework for future research and policy change to build on, adapt, and extend to other settings or clinical areas. Furthermore, the knowledge generated and mobilized from this work can provide evidence for a patient-centric research action plan with the aim of improving mental health service navigation and accessibility. Finally, this project integrates important elements of teamwork and knowledge translation.",,-99,Centre for Addiction and Mental Health (Toronto),7751.3,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26611,449645,Proteomic analyses of how ZIKV infection modulates the expression of astrocytic proteins involved in synaptogenesis and other synaptic controls,"Zika virus (ZIKV), one of the re-emerging viruses, is transmitted via a mosquito vector. It is an obligate micro-organism that requires host cells to replicate. To date, 87 countries show evidence of mosquito-borne ZIKV transmission. In Canada, 31,587 cases have been reported in 2018 with 3,473 of them having been confirmed via the lab results. Climate change potentially increases the incidence of mosquitoes impacting the viral transmission (Aedes aegyti prefers warm and rainy weather conditions). So far, no vaccine/treatment exists for ZIKV infection and its infection leads to numerous neurological conditions like microcephaly, abnormal brain development, Guillain-Barre syndrome, eye abnormalities, fetal growth impairment and fetal death. Inside the brain, specialized cells called astrocytes support neurons. Since these cells are one of the major brain cell populations and ZIKV is known to infect these cells, many of the above mentioned neurological diseases are associated with ZIKV impairing the astrocytic function and protein expression. According to my recently published data in 2019, ZIKV has been found to alter the expression of many such proteins like SPARC, STAT3, HSD17B10 and THBS 1/2, most of which are involved in the regulation of synapses. Therefore, this current project aims to focus on performing a proteomic screen looking at the impact of ZIKV infection in human astrocytic cells using mass spectrometry. Through this project, specific proteins inside ZIKV infected human astrocytes will be identified and their role in ZIKV replication, protein synthesis and assembly will be studied. This is crucial in understanding the mechanism of action of ZIKV as it will enable us to find novel therapeutic targets for various Zika antiviral treatments in the future.",,-99,University of Manitoba,13459.8,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P26612,475690,The Role of Cdc42 in Regulating the Production and Release of Pro-inflammatory Cytokines in Airway Epithelial Cells.,"More than 3.8 million Canadians are living with asthma. Chronic lung inflammatory diseases such as asthma and COPD (chronic obstructive pulmonary disease) are characterized by secretion of harmful proteins that trigger destructive inflammation. These proteins, known as cytokines, are the body's natural alarms that notify the immune system against the presence of pathogens and toxins. However, excessive secretion of these proteins, especially in response to harmless allergens, can be detrimental in the lung milieu as it can cause extensive tissue damage to the airways in chronic inflammation. This process is also particularly pivotal in viral infections such as in COVID-19, where the 'cytokine storm' is conducive to multi-organ failure and even death. Although these proteins can be secreted by a variety of different cell types in the body, the epithelial cells that line the pulmonary tracts are particularly important secretors of these cytokines. This is because these cells are regularly the first cells to come into contact with external triggers and initiate an inflammatory response. In fact, the secretion of cytokines by epithelial cells is known to drive downstream inflammation by recruiting and activating immune cells. This ultimately results in the instigation of a robust (and threatening) pro-inflammatory reaction. Currently, the signalling and trafficking pathways that control the release of cytokines from epithelial cells are vaguely illustrated. In our project, we propose a group of signalling proteins, known as Rho GTPases, as underlying regulators of this process of cytokine release. These proteins are known to transduce external signals into cues for gene expression and secretion. However, their role in pro-inflammatory cytokine production and secretion within lung epithelial cells remains unknown. We use cellular models of asthma and viral infections to mimic inflammation and characterize the specific contributions of Rho proteins within these processes.",,-99,University of Alberta,77083.46,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis,2022 +P26615,467728,Solving the genomics of unsolved rare life-threatening COVID-19 using genome sequencing,"COVID-19, caused by the SARS-CoV-2 virus, has been declared a pandemic and is one of the most urgent global health crises. The phenotypes of COVID-19 are highly heterogeneous, and a major challenge is the early recognition of severe COVID-19 to support early clinical intervention and targeted therapy. Certain individuals may have a higher risk of severe disease, for example, people with pre-existing respiratory, cardiac, or immune disorders. However, in some rare cases, severe disease occurs in young individuals without any risk factors and is unexplained. We hypothesize that severe illness with COVID-19 in people who do not otherwise have pre-existing risk factors is attributable to monogenic causes in some cases. We have an opportunity to study this in participants recruited to the Alberta Host Genetic Susceptibility project (led by Pfeffer lab) within Hostseq, which focused on younger patients who required hospitalization and did not have pre-existing comorbidities. We will apply cutting-edge genome sequencing (GS) analytical approaches developed by Tarailo-Graovac lab with correlation to comprehensive clinical data. We have successfully applied GS methods to unravel the complex genetic mechanisms underlying rare undiagnosed diseases by identification of previously missed variants of interest. I will work with genomes of the rare severe patients with COVID-19 using the ""three stages"" and ""two levels"" strategy to identify causative genes and complex genetic scenarios in independent cohorts. We will apply the background variant information from the Hostseq database to help narrow down the candidates. As such, this work has the potential to build a diagnostic workflow for rare, life-threatening COVID-19 patients and provide clues for identifying individuals predisposed to severe COVID-19 outcomes.",,-99,University of Calgary,54259.11,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease susceptibility | Prognostic factors for disease severity",2022 +P26619,470464,Ultrapotent and broadly neutralizing engineered biologics as therapeutics for SARS-CoV-2,"The COVID-19 pandemic is caused by an infection with the SARS-CoV-2 virus. Antiviral antibodies targeting this virus can block its ability to infect individuals, and thus, they are a promising treatment. Though natural antibodies derived from infected individuals are a common source of antiviral antibodies, they are limited in their ability to resist viral mutations and have consequently been rendered ineffective as the pandemic has dragged on and viral variants have emerged. In contrast, advanced antibody engineering technologies enable these limitations to be overcome without increasing costs. Leveraging our expertise in antibody engineering, we have generated antibodies targeting multiple sites on the SARS-CoV-2 virus that are essential for entry of the virus into cells, and we have shown that treatment of cellular and animal models of infection with these antibodies can reduce infection. In this project, we propose to further engineer these antibodies to enhance their efficacy and ensure that they remain effective against emerging variants of the virus. To achieve this, the antibodies will be optimized to potently neutralize viral infections, including those arising from both existing and future variants of concern. We will then test the antibodies in cellular and animal models of infection to gauge their efficacy in direct comparison with clinically authorized antibodies, to validate the superiority of our approach. Overall, we aim to create an effective anti-COVID19 therapeutic drug candidate that will remain effective against diverse versions of the virus, to provide a direly needed treatment for infected patients. These new antivirals should help reduce the burdens on health, economy and society that the pandemic has imposed on Canada and the world.",,-99,University of Waterloo (Ontario),636313.5,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P26625,466312,A phase 2 trial to evaluate safety and immunogenicity of a next-generation COVID-19 vaccine delivered by inhaled aerosol to humans,"Despite the benefit of current COVID vaccines in preventing severe disease and death, these vaccines are relatively poor at preventing infection with new variants like Omicron and work less well in the elderly and people with weak immune systems. There is an urgent need to develop new, next generation vaccines. As leaders in respiratory mucosal immunity, we have shown how delivering a vaccine directly to the lung by inhalation leads to better protection from infection than an IM injection. Before COVID, we were studying a new viral-vectored vaccine for TB inhaled into the lungs in healthy volunteers. We showed that this vaccine was safe and that good immune responses to TB were made in the lungs. With the arrival of COVID, we developed next generation multivalent COVID-19 vaccines active against not only the spike protein but also internal viral proteins that do not mutate, even in variants. After showing that these vaccines were safe and protected against COVID infection in animals, we began a human trial with 30 healthy persons who had at least 2 doses of a mRNA vaccine and are studying in detail the immune responses in the lung and blood. In our planned placebo-controlled Phase 2 study, we will enroll 500 participants from at least 3 clinical trial sites across Canada, to get more confidence in the safety of the inhaled route of administration and make the results more generalizable by enrolling older persons and those with underlying health conditions. We will gather safety and measures of immune responses to support a phase 3 clinical trial, with the goal of licensing and marketing our made-in-Canada vaccine and the aerosol method of administration. We expect this vaccine approach to be effective in breaking the cycle of new variant, poor vaccine performance, transmission and infection. The research team is led by Dr Fiona Smaill and includes members with a rich experience in vaccine clinical trials, vaccine manufacturing, aerosol delivery, and immunology.",,-99,McMaster University,6407469.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2022 +P26630,468867,Advancing Equity-Based Pandemic Preparedness Through Intersectional Analysis,"Like previous pandemics, the effects of COVID-19 have not been experienced equally, with those already experiencing health inequities most effected. Despite concerted efforts to apply gender-based analysis plus (GBA+) within the COVID-19 response, Canada was ill prepared to address the unequal effects of the pandemic due to its lack of adequate consideration of health inequities within pandemic preparedness planning. This project aims to build off of ongoing research on the intersectional effects of COVID-19, to inform equity-based pandemic preparedness through innovative approaches to guidance and monitoring. Learnings from the COVID-19 response will be applied to the following objectives: A) to better understand public health policy opportunities and challenges related to mitigating the unequal effects of health crises in Canada; B) to develop guidance and monitoring tools for integrating intersectional analysis into pandemic preparedness. Applying an intersectional feminist approach, research will include scoping reviews, policy analysis and key informant interviews with civil society and policy actors. Outputs will include an equity matrix monitoring framework for pandemic preparedness and policy guidance on integrating intersectional analysis into preparedness planning. Outcomes will promote greater consideration of intersectional effects on priority populations within pandemic preparedness and improve resilience to future pandemics. Through the evolution and creation of tools focused on intersectional inequities and pandemic preparedness, this work will support systemic and policy changes towards pandemic-ready health systems and policy structures.",,-99,"Simon Fraser University (Burnaby, B.C.)",74336.93,Human Populations | Other,Unspecified,Unspecified,Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Research to inform ethical issues in Research | Policy research and interventions | Social impacts,2022 +P26631,499113,Ethical Preparedness: 'Ethics to Policy' in Public Health Emergency Preparedness and Response,"This research aims to enhance 'ethical preparedness' for infectious disease emergencies, i.e., being ready as a society not just to deal technically with an infectious disease emergency (e.g., epidemic, pandemic), but to do so in a way that is ethically appropriate and justified in ethical terms. The achievement of this objective is contingent on two activities: (1) rigorous and systematic research on key ethical issues expected to arise in future infectious disease emergencies, with a specific focus on how such issues have been shaped by Canadians' experiences with the COVID-19 pandemic and responses to it; and (2) effective translation and integration of such research and knowledge into decision-making in infectious disease emergencies (i.e., 'ethics to policy'). Working with public health decision-makers locally, provincially, and internationally, this program of research will significantly advance both of these aims in Canada by examining three central ethical challenges identified by policymakers that require scrutiny in the post-COVID-19 landscape (that is, following the advent of COVID-19), and by doing so in a way that is oriented toward the practical realities faced by decision-makers. These challenges include: (a) the equitable allocation of scarce resources like vaccines, therapeutics, and diagnostics; (b) balancing the rights of the individual and the interests of society when using population health interventions like isolation, quarantine, and mandates; and (c) the design and conduct of research in and for infectious disease emergencies. The principal outputs of this program of research will include a comprehensive 'Infectious Disease Ethics Playbook' that offers policy-oriented guidance in these domains, designed for use by decision-makers, as well as the establishment of best practices for generating ethical information, analyses, and advice for decision-makers in real-time when making decisions during infectious disease emergencies.",,-99,University of Western Ontario,851777.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Research to inform ethical issues,Research to inform ethical issues in Research | Research to inform ethical issues in the Allocation of Resources | Research to inform ethical issues in Governance,2023 +P26638,460464,Utilization-Focused Evaluation of Virtual Physician Care Use in Long-Term Care Homes Across a Regional BC Health Authority (ViP LTC Study),"Many doctors started to routinely care for residents in long-term care homes virtually by video, phone, e-mail, or text during the COVID-19 pandemic. This was done to stop the spread of COVID-19. Concerns have been made by doctors and staff in long-term care homes about how this affects the quality of residents' care and the well-being of residents, their family caregivers, doctors and health care staff. We will evaluate the use of virtual doctor care in long-term care during the pandemic in Fraser Health region in British Columbia. This will be done through capturing the views of both care providers and care recipients. We will interview residents living in long-term care home and their family caregivers to capture views on virtual doctor care and preferences compared to in-person doctor care. Also, we will run focus groups with doctors and health care staff involved in virtual care in long-term care homes to assess their views and preferences for caring for residents virtually. Overall, we want to assess what barriers and enablers exist for virtual doctor care that is fair and yields good results and value for residents and staff in long-term care. Our approach will involve ongoing team work between researchers and end users. End users will include: key decision makers, residents, family caregivers, doctors and health care staff in long-term care and virtual health at Fraser Health. The results of this study will inform decision makers and front-line end users about best practices for virtual doctor care now and after the pandemic. They will also be used to develop practical tools for end user. For example, a note for decision makers, a picture plan for doctors and staff and a picture plan or short video for residents and family caregivers in long-term care homes are planned guide best practice in virtual doctor care.",,-99,"Fraser Health Authority (Surrey, BC)",78976.51,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Health Personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health information systems,2021 +P26639,468877,Utilization-Focused Evaluation of Virtual Family Visits in Assisted Living and Long-Term Care Homes Across a Regional BC Health Authority (VFV Study),"Virtual family visits by video, phone, e-mail, or text have been the only way for some residents in care homes to connect with their family during the COVID-19 pandemic. This was due to limits placed on in-person visits to lower the risk of outbreaks in care homes. Bans on visits left residents lonely and depressed. It also reduced the wellbeing of families not able to visit their loved ones in care homes. Virtual family visits might help, but concerns have been raised about issues with fair access and privacy. We will evaluate the use and value of virtual family visits in assisted living and long-term care homes during the pandemic in the Fraser Health region in British Columbia. This will be done based on the views of residents, their families and staff in care homes. We will interview residents living in assisted living or long-term care homes and their family members to hear their views on virtual family visits and preferences compared to in-person visits. Also, we will run focus groups with care home staff that support virtual family visits to assess the impact on their work load and lessons learned. Overall, we want to assess what barriers and enablers exist for virtual family visits that are fair and give value for residents, their families and staff in care homes. Our approach will involve ongoing team work between researchers and end users. End users will include: key decision makers, residents, family members, and care staff supporting virtual family visits in assisted living long-term care in Fraser Health. The results of this study will inform decision makers and front-line end users about best practices for virtual family visits now and after the pandemic. They will also be used to develop practical tools for end users. For example, a note for decision makers, a picture plan for care staff and a picture plan or short video for residents and families in assisted living and long-term care.",,-99,"Fraser Health Authority (Surrey, BC)",78410.34,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery | Health information systems,2022 +P26646,468882,Strengthening Capacity for Public Health Leadership and Decision-Making: The Contribution of Case-based Learning,"The COVID-19 pandemic has refocused attention globally and in Canada on the capacities and performance of public health systems within larger government and non-government structures. Previously, our team studied how public health systems and decision-makers in Canada and other jurisdictions are organized and interact with other political and social actors, resulting in policies to respond to acute public health needs, such as COVID-19. Our approach focuses on the effect of institutions, politics, public health system organization, and governance (IPOG) on the public health response. Our proposal aims to strengthen the capacities of public health trainees and in-service public health decision-makers and practitioners to engage with these 'upstream' factors, in order to advance objectives of public health improvement in complex governmental and non-governmental environments. We hypothesize that these capacities can be strengthened through competency-focused education and practice interventions. Through the IPOG framework we focus on ""governance"" as decision-making process, which can be improved by greater preparation and skills in navigating organizational and political factors. We further hypothesize that problem-oriented, case-based teaching can strengthen competencies needed in this domain. Hence, in keeping with the 2021 PHAC report, we suggest that there is potential to improve the competencies for public health practitioners to interface with political leaders as well as engage with other key government and non-government actors. In partnership with knowledge users, the project will generate and apply new knowledge by outlining competency gaps pertaining to IPOG in public health training programs in Canada; develop, use, and evaluate teaching cases using multi-media video accompanied by a detailed teaching guide; and make them available as open-access resources. Keywords: Public Health, Competency, Teaching Cases, Public Health Trainees, Political, Government",,-99,University of British Columbia,78410.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P26647,480935,Fostering a research collaboration on new global trends in violence against health workers,"Violence against health care workers is a growing concern, exacerbated during the COVID-19 pandemic due to divisive rhetoric, mistrust of health professionals, and politicization of COVID policies. The health sector contributes approximately 25% of all reported workplace-related violent incidents. The world currently faces a dire health worker crisis, in terms of staffing shortages, burnout and attrition. This crisis has major consequences for health service access and availability globally. Rising violence and a lack of protections for HCWs are potential contributors to these challenges. There is a major gap in understanding emerging forms of violence against health workers. These forms of violence are seemingly shaped by multiple, interconnected contextual factors, including growing societal polarization, mistrust of health workers, and evolving geopolitical trends, including those pertaining to conflict. These emergent and life-threatening forms of violence, occurring in both workplace and non-workplace settings, include kidnapping, murder, and physical assault by non-state actors, such as militant organizations. These types of violent events appear to be more common in certain low-and-middle-income countries (LMICs), even in non-conflict-affected settings, but often linked to broader socio-economic, political and security-related reasons. This proposal aims to initiate planning for a program of work that explores global trends, drivers, and policy responses to violence against health care workers, and develops a case study of violence against these workers in Nigeria, a country that has experienced a wave of these types of events in recent years. The activities to be sponsored by this grant include a rapid sense-making appraisal of current literature, as well as virtual and physical meetings with Nigeria research partners and knowledge users. The activities sponsored by this grant will facilitate a CIHR Project Grant on this topic within one calendar year.",,-99,University of British Columbia,15007.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P26653,477776,The Power over Pain Portal for Youth with Chronic Pain,"The COVID-19 pandemic is one of the greatest threats to youth mental health in generations. Youth today report increased pain complaints, and without treatment, these will become chronic. Chronic pain (CP) currently affects 1 in 5 youth and has devastating impacts on families. The COVID-19 pandemic has made access to CP care more difficult. However, a ""Stepped care"" approach is a promising way to improve access, as it tailors care based on the severity of symptoms. The goal of the Power over Pain Portal was to develop a centralized virtual pain hub that empowers youth living with CP to engage with evidence-based pain interventions in a stepped-care manner. We did this in four phases. Surveys and interviews were first conducted with healthcare providers (Phase 1), as well as children with CP and their families (Phase 2) to determine the impacts of COVID-19. We then generated evidence to inform the rapid delivery of tailored stepped care solutions (Phase 3). Based on these findings, we co-created (with youth with CP) and designed the Power over Pain Portal (Phase 4), in the hopes of addressing these challenges and improving access to evidencebased pain care. Our video presents the Power over Pain Portal as an online portal that empowers youth living with chronic pain to engage with evidence-based pain interventions in a stepped care manner. The gaps to evidence-based care identified by youth, and the co-design process will be discussed, as well as future considerations and the implementation of the Power over Pain Portal.",,-99,Hospital for Sick Children (Toronto),383.31,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26660,429694,Bespoke transition state analog inhibitors of SARS-CoV-2 3CL and PL proteases,"SARS-CoV-2 is devastating global health and economies. Rapid development of antiviral drugs is critical to treat disease in the short term and beyond. Logical antiviral targets are the proteases 3CLpro and PLpro, responsible for processing of long chains of linked viral proteins produced during viral reproduction. 3CLpro and PLpro are enzymes that harness pac-man like activity to clip the chains into individual proteins. This cleavage process is essential for formation of new disease causing virus. If you block the pac-man activity, you stop the virus in its tracks. Similar types of viruses have been targeted very successfully by drug development in other important global viruses such as HIV. Understanding inhibitor binding to 3CLpro and PLpro at the atomic level is central to antiviral drug development. We are harnessing our significant expertise in xray crystallography and single particle cryoEM, biophsyical techniques that allow us to determine atomic pictures of these proteases in the presence of bound drug. Leveraging our prior work on similar enzymes with international leading antimicrobial pharmaceutical teams we have identified tight binding drug leads that take advantage of the unique features of these enzymes. We aim to optimize these compounds through structure-guided techniques (using our atomic blueprints so to speak) and the antiviral drug discovery pipeline of our industry partner.",,-99,University of British Columbia,286729.69,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P26661,443340,COVID-19 Variant Network - Bespoke transition state analog inhibitors of SARS-CoV-2 3CL and PL proteases,"SARS-CoV-2 is devastating global health and economies. Rapid development of antiviral drugs is critical to treat disease in the short term and beyond. Logical antiviral targets are the proteases 3CLpro and PLpro, responsible for processing of long chains of linked viral proteins produced during viral reproduction. 3CLpro and PLpro are enzymes that harness pac-man like activity to clip the chains into individual proteins. This cleavage process is essential for formation of new disease causing virus. If you block the pac-man activity, you stop the virus in its tracks. Similar types of viruses have been targeted very successfully by drug development in other important global viruses such as HIV. Understanding inhibitor binding to 3CLpro and PLpro at the atomic level is central to antiviral drug development. We are harnessing our significant expertise in xray crystallography and single particle cryoEM, biophsyical techniques that allow us to determine atomic pictures of these proteases in the presence of bound drug. Leveraging our prior work on similar enzymes with international leading antimicrobial pharmaceutical teams we have identified tight binding drug leads that take advantage of the unique features of these enzymes. We aim to optimize these compounds through structure-guided techniques (using our atomic blueprints so to speak) and the antiviral drug discovery pipeline of our industry partner.",,-99,University of British Columbia,78392.55,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P26670,467041,Investigate the role of parenteral vaccine-trained tissue-resident macrophages in host defense against heterologous bacterial infections,"Immunological memory has traditionally been solely attributed to T and B lymphocytes in the adaptive immune system. Recently, the concept of immunological memory has been expanded to include innate immune memory, which can be defined as an altered state of the innate immune system after primary exposure to an antigen or microbe that will modify its responsiveness to the same or different antigen/microbe. Trained innate immunity (TII), a subset of innate immune memory, is characterized by cellular and epigenetic changes, along with protection against heterologous infections. Ample evidence of TII induced by systemic administration of certain vaccines exists. However, there are many knowledge gaps about the capacity of systemic vaccination to invoke TII in local tissue-resident cells. Given the recent and widespread human vaccination with mRNA-based and viral-vector-based SARS-CoV2 vaccines, it is of great relevance to study whether these vaccines are capable of inducing TII in local tissue-resident cells. This project will employ a murine model to examine the capacity of parenteral delivery of mRNA-based and viral-vector-based vaccines to induce TII in respiratory-mucosal tissue-resident macrophages, and the mechanisms underlying any observed training. Secondly, the project will seek to determine if TII invoked by these vaccines will lead to protection against heterologous bacterial infections and if so, how this protection is attained. In the recent climate of the COVID-19 pandemic, with mass global vaccinations and rapidly evolving variants that may evade current vaccines, it is of high importance to investigate the potential of SARS-CoV2 vaccines to evoke TII. Furthermore, future vaccination strategies would benefit greatly to evoke both innate and adaptive immunity.",,-99,McMaster University,13724.56,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +P26673,448920,Understanding and treating the adverse effects of COVID-19 on the brain,"A marked proportion of COVID-19 patients develop a spectrum of neurological symptoms ranging from acute, very severe outcomes like stroke, to longer term effects like headache, trouble thinking clearly, anxiety, and depression. Some of the more common symptoms like headache, trouble thinking clearly, anxiety, and depression (more common in women) can last long after the infection has cleared. These neurological symptoms are consistent with those seen when the body mounts a defense against an infection, in a process called inflammation. The body releases factors into the bloodstream called inflammatory mediators, and these can make their way into the brain. Once in the brain, these mediators trigger special brain immune and glial cells to become 'reactive'. In the reactive state, immune and glial cells start to dismantle and destroy neuronal connections, which can result in impaired decision-making, as well as anxiety and depression. This study will investigate how COVID-19-associated inflammation in the body leads to changes in the brain, specifically changes in these immune and glial cells, as well as in neuronal connections - and will also test a drug to prevent or reverse these changes. This drug blocks the function of a protein that normally regulates neuronal connections and immune and glial cell responses, and is already approved for use in humans. To do this work, we will use our skillset in microscopy and biochemistry, and will capitalize on our expertise in neuroinflammation and immune and glial cell biology, as well as our understanding of the regulation of neuronal connection structures. The outcomes of this work will provide critical new insight into brain changes resulting from COVID-19, which will inform diagnosis and treatment. Moreover, we will directly test the effects of an approved drug, and this could lead to clinical trials for repurposing this drug to treat COVID-19, thereby opening up new avenues for therapeutic intervention.",,-99,University of Victoria (British Columbia),232772.33,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2021 +P26674,448827,"Using Facility Administrative Data to Inform Prevention and Improve the Clinical Management of COVID-19 Infection, Illness, Hospitalization for Nursing Homes and Retirement Homes","Older adults are most vulnerable to developing complications from COVID-19 leading to hospitalization or death. Among older adults, the COVID pandemic has had a profound impact on long-term care/nursing home residents who account for 60% of all COVID related deaths in Canada, and internationally. By virtue of living in congregate settings nursing home residents are more likely to contract COVID, and the underlying medical conditions that cause them to need nursing care make them particularly susceptible to COVID complications. This context requires knowledge of both i) individual-level chronic conditions, cognitive and physical impairments, and age-related disabilities, and ii) home-level factors including the physical environment, and staffing levels and mix. Moreover, individual- and home-level characteristics interact and must be studied jointly to understand, and reduce, COVID infections and complications. To date, these forces affecting resident vulnerability have not been addressed jointly. There is a need to disentangle individual-level features such as functional and physical impairments, and home-level features such as the percentage of part-time workers in a unit. However, not all features can be disentangled. Some operate jointly, not independently, and characterizing the interactions between individual and home characteristics is a key goal. We will address this by building a data repository combining both home-level and resident-level data. This will allow us to build prediction tools, including machine learning algorithms addressing interactions, to differentiate patients who may or may not do well with COVID, or its variants, in real-time to inform rapid decision-making. The unique contribution of our study is to employ electronic medical record (PointClickCare) data, including clinical frailty measures that are not available from other public health and provincial data centres, together with human resource and other operational administrative data.",,-99,McMaster University,264809.11,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Individuals with multimorbidity | Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing | Digital Health,,,Canada,,Epidemiological studies | Clinical characterisation and management,"Disease susceptibility | Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +P26675,469320,Pay Gaps in Canadian Medicine,"Understanding physician behaviour and its impacts on healthcare delivery is a long-standing topic in health economics, health services and medical research. Physician payment and delivery systems incorporate numerous incentives that have implications for access, service delivery and patient outcomes. This project will contribute much needed empirical evidence on the physician sector, specifically on physician pay gaps related to gender, race/ethnicity, foreign-training and immigration status. We will study all physicians, with a particular focus on the largest specialty group, Family Medicine. While our previous research has addressed aspects of gender gaps in physician pay and labour supply (weeks and hours of work), we will use the theory of intersectionality to recognize how other aspects of social identity such as race and immigration status may intersect with gender to influence earnings. In Ontario, the Ministry of Health and the Ontario Medical Association (OMA) reached a tentative Physician Services Agreement (released March 3, 2022) that sets out a process to initiate steps to close the gender pay gap. In part, this research proposal is interested in informing the implementation of this process, potential similar aspects of Agreements in other provinces, as well as potential extensions. Five distinct data sources providing alternative insights will be employed: Statistics Canada Censuses and Labour Force Surveys, Canada Revenue Agency taxation records, electronic medical records, a survey of physicians, and qualitative data from physicians. Women in the physician workforce appear, on average, to have different approaches to practice than their male colleagues that are only superficially understood. We will examine the sources and ramifications of these differences as well as those due to race/ethnicity, foreign training and immigration status. The initial impact of COVID-19's shock on physician labour supply and earnings gaps will also be explored.",,-99,McMaster University,149549.28,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Social impacts | Other secondary impacts | Health workforce,2022 +P26678,477773,Children's Return to Play During COVID-19,"This video tells a story about the impact of the COVID-19 pandemic on parents' and their children's physical activity and sport behaviours. In Ontario, various COVID-19 public health measures were enforced after the onset of the pandemic in 2020 to reduce the spread of the virus. Such measures included various closures of physical activity-supporting environments, such as: outdoor recreation facilities (e.g., basketball courts), schools, and community centres. These closures left many parents struggling to keep themselves and their children active while spending large amounts of time at home. This video reveals perspectives from Ontario parents and children during pandemic times, concerning their movement behaviours and overall well-being. The video aligns with the mandate as participating in physical activity during childhood plays an important role in supporting optimal growth and development. Not only does physical activity promote good health, but it also plays a role in chronic disease prevention, supports social connections, and mental health. As many parents and children had to adapt their lives (e.g., shift from attending in-person school/work each day to remote learning/working), the lessons learned from the COVID-19 pandemic can inform future instances of extended stay-at-home periods; specifically, findings from our study (and video) provide examples of what families can do to maintain their healthy movement behaviours, and to prevent social isolation during stay-at-home periods to ensure optimal growth and healthy development milestones are being met.",,-99,University of Western Ontario,383.31,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P26681,480781,Developing an Ontario community pharmacy-based Minor ailment service Evaluation framework (DOME).,"The COVID-19 pandemic created a surge in demand for healthcare. In response to this surge in demand, the Ontario provincial government introduced a new service across community pharmacies. This is the minor ailment prescribing that launched in January 2023. The minor ailment service allows pharmacists to prescribe for thirteen approved medical conditions. Community pharmacists are easily accessible in the community and provide advice to patients seeking help for many conditions. This new service will affect the health of all Ontarians, so it is important to evaluate its us. To ensure the most optimal evaluation is conducted, it is important to bring together stakeholders, policymakers, patients and researchers. So our group aims to use this funding to bring these people together to (1) develop a set of aligned goals and priorities for the evaluation of the service in Ontario and (2) to co-identify objectives and think about how we would launch these important studies. We will do this is in three parts 1) Pre-workshop (2) Workshop and (3) Post-workshop. Initially, a series of focus group discussions will be conducted with stakeholders, policymakers, patients and researchers to determine to get their perspectives. The workshop will then bring together all participant groups for a one-day face-to-face workshop to discuss the results of the focus groups and lead participants through a priority-setting exercise. Finally, the post-workshop phase encompasses sharing the results of the workshop and allowing for final feedback from participants on the evaluation required. This proposal is the first step to launching an important number of studies to make sure that the newly launched pharmacy-based minor ailment service is evaluated and helps inform similar programs across Canada.",,-99,University of Toronto,37426.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health leadership and governance,2023 +P26683,495256,Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study,"Characteristics of the SARS-CoV-2 antibody response associated with COVID-19 severity and protective immunity remain unclear. Here we assessed SARS-CoV-2 antibody responses in GENCOV participants to identify differences following COVID-19 diagnosis and/or vaccination. Blood samples were collected 1-, 6- and 12-months following SARS-CoV-2 infection and/or vaccination. Participants who were vaccinated, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody titers compared to unvaccinated participants. In unvaccinated participants, increasing age and illness severity were associated with significantly higher antibody titers. Participants who were vaccinated after infection (hybrid immunity) had consistently higher antibody titers compared to participants who were infection-naïve or vaccinated prior to their infection ( breakthrough infections) suggesting that timing of vaccination played a role in the antibody response. At all time points, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody titers. These findings highlight various patient factors, including vaccination, which contribute to maintaining robust and durable SARS-CoV-2 antibody responses.",,-99,Sinai Health System (Toronto),111.1,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P26688,471053,Canada-Africa Monkeypox Partnership (CAMP): Characterizing transmission dynamics and evaluating medical countermeasures to inform the clinical and public health response to Mpox,to be completed,,-99,Unity Health Toronto,2299861.81,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Investigation of zoonotic transmission & reservoirs | Epidemiology & transmission dynamics of mpox including sexual transmission.,Canada,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,Animal source and routes of transmission | Disease transmission dynamics | IPC in health care settings | IPC at the human-animal interface,2022 +P26690,480888,Aerobic Exercise Recommendations to Optimize Best Practices In Care after Stroke: AEROBICS 2024 Update,"There are 400,000 people living with stroke in Canada and this number is expected to nearly double in the next 20 years. Research has shown that exercise is an important part of healthy living after stroke, but people living with stroke remain physically inactive. To help health providers promote exercise after stroke, a meeting was held in 2010 with an international group of experts to review the body of research, and the ""Aerobic Exercise Recommendations to Optimize Best Practices in Care after Stroke"" was developed in 2013 (AEROBICS 2013). Research and healthcare evolve over time, and the recommendations were updated in 2019 (AEROBICS 2019) to include the latest evidence and ensure the recommendations were current for stroke rehabilitation programs. It is now time to update AEROBICS again. New research continues to emerge that build our understanding about the benefits of exercise after stroke (for example, on thinking and memory), different ways to prescribe exercise (for example, high-intensity interval training or virtual exercise), and how we can best support both men and women to participate in exercise (considerations of sex and gender in exercise after stroke). We also need to consider the impacts of COVID-19 on exercise training after stroke. We plan to hold two half-day virtual meetings with researchers, physical therapists working in stroke rehabilitation, and people living with stroke to review research published since 2019 to develop AEROBICS 2024. Our team members are from all across Canada, and we also have experts from the US. We will also consult with our Stroke Advisory Group, a local group of 5 people with a range of backgrounds, men and women, and experiences from how the stroke affected them, which will help ensure that AEROBICS 2024 suits the needs of the broader stroke community.",,-99,McMaster University,11255.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26694,467194,Online Learning in Undergraduate Nursing Education: Screening for E-learning Readiness as a Predictor of Engagement and Academic Achievement,"There are numerous advantages to a bachelors degree in nursing. Bachelor-trained nurses report increased levels of job satisfaction due to a greater sense of autonomy and more diverse career opportunities. Furthermore, hospitals with higher numbers of nurses with a bachelors degree have lower rates of patient complications, reduced lengths-of-stay and fewer patient deaths. Currently, less than 50% of all nurses in Quebec hold a bachelors degree and Quebec is the only Canadian province which does not require a bachelors degree as the minimum education to practice. The Ingram School of Nursing (ISoN) has been offering the Bachelor of Nursing (Integrated) (BNI) Program for students with a Quebec CEGEP diploma in nursing since 2004 in an on-campus format. In the fall of 2021, an online version of this program was launched to improve accessibility and flexibility for those wishing to pursue their undergraduate nursing education. The COVID-19 pandemic highlighted the challenges some students face with online learning. The proposed research project aims to determine the characteristics of students that predict success and satisfaction with the chosen stream (online vs. in-person). Existing data on characteristics, 1st year course grades, and reported levels of satisfaction from second-year students in both streams will be analyzed. Group interviews will also be conducted with students in both streams. Based on the results, an assessment tool will be developed to help future applicants determine which mode of learning is best suited to their unique needs. Ultimately, findings from this research may help inform strategies to increase the number of bachelor-trained nurses leading to improved nurse satisfaction and better patient outcomes.",,-99,McGill University,13724.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2021 +P26695,479591,The Impact of COVID-19 on Francophone and other Minority Language Groups Living in Long-term Care or Receiving Home Care,"To be able to live independently and safely, older adults depend on support from publicly funded home care and others live in long-term care (LTC) homes where they receive 24/7 board and care. These individuals have been especially hard hit by the COVID-19 pandemic. Many home care clients and LTC residents are members of minority groups, which compounds their vulnerability. Past research has shown that during the pandemic, there have been inequities in the healthcare and outcomes of ethnocultural minorities and marginalized populations, such as immigrants and ethnic minorities. An additional vulnerability for minority groups is the potential impact of linguistic barriers in accessing health care services; negative impacts that has been noted prior to the pandemic. To date, no studies, however, have examined the effect of the COVID-19 pandemic on Francophones and other linguistic minority groups receiving home care or residing in LTC homes. This study will use administrative data to 1) describe and compare the sociodemographic characteristics and health services of linguistic groups (Anglophones, Francophones, and allophones) receiving home care or residing in LTC homes; 2) evaluate and compare the quality of care received by each linguistic group of LTC residents and home care recipients during the different phases of the COVID-19 pandemic; 3) measure and compare COVID-19 outcomes by linguistic group among LTC residents and home care recipients; and 4) identify what factors contribute to COVID-19 outcomes among minority linguistic groups. Information about COVID-19 outcomes for LTC residents and home care recipients is critical for the ongoing efforts to mitigate the impacts of the ongoing COVID-19 pandemic. The results of this project will help to inform strategies to address inequities in Ontario's health care system - particularly among linguistic minorities.",,-99,"Institut du Savoir Montfort (Ottawa, ON)",407845.81,Human Populations | Other,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P26699,468211,Improving access to breastfeeding support in British Columbia: A collaborative planning project,"Breastfeeding has many health benefits for both infant and mother. While it is recommended that new mothers exclusively breastfeed for the first six months postpartum, with continued breastfeeding for up to two years and beyond, many women and birthing people experience breastfeeding challenges. Poor latch, pain, and lack of support can impact breastfeeding goals. These challenges can be heavily influenced by social inequities, parental leave, and societal pressures, particularly among disadvantaged populations in Canada and around the world. It is important for postpartum women to receive breastfeeding support from healthcare professionals, especially during the COVID-19 pandemic where in-person contact is limited. Therefore, this planning project will establish key networks and resources around optimal breastfeeding support in British Columbia. Specific objectives are to build partnerships, conduct a needs assessment, and create a research agenda to develop and evaluate a breastfeeding support intervention study in the province. We expect to identify key aspects of virtual and in-person support that will create a thorough and meaningfully designed breastfeeding intervention study, which will ultimately lead to higher rates of breastfeeding initiation, duration, and exclusivity, as well as improved user satisfaction and self-efficacy among parents and families across BC. Breastfeeding is an important, cost-effective strategy that must be supported effectively to improve health outcomes for mothers and children.",,-99,University of British Columbia,7751.3,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26702,480791,Redesigning Paramedicine in Canada: An Underutilized Health Human Resource in a Healthcare Crisis,"Of the more than 6 million Canadians without a family doctor, at least a third say they have been looking for one for more than a year. The COVID-19 pandemic exposed fault lines in Canada's healthcare system that have been growing for decades and now, with nearly 20% of family doctors in Toronto planning on closing their practices in the next five years. Health care has reached a crisis point. Experts agree that innovative solutions are needed to improve health care coordination and access. Paramedics are uniquely positioned to respond to the crisis, with more than 35,000 currently providing care across the country. The problem, however, is that the traditional 'respond-and-transport' model of care from which paramedics have evolved is no longer meeting the needs of Canadians. As many as 65% of patients brought to hospital by paramedics are discharged directly from the emergency department. Until recently, there has been little consensus on the changing role paramedics can - or should - have in our communities, but in 2021, a national panel of experts released a visioning document for the future of paramedicine in Canada. Among other things, this document calls for paramedics to provide care along the full health and social continuum - a bold strategy that could improve access to health care in Canada. What is needed now are concrete solutions to realize the potential of paramedics as an untapped healthcare resource. Our team will assemble a pan-Canadian network of industry experts, community leaders, patients, and policymakers to develop concrete strategies to optimize the integration of paramedics into contemporary health care, guided by the principles articulated in the national visioning document. By bringing together a diverse group of stakeholders, we will bridge the gap between service delivery and community needs in paramedicine and improve access to health care for Canadians.",,-99,University of Toronto Scarborough (ON),7503.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health workforce,2023 +P26704,459547,"Adapting the Sex Education by Theatre (SExT) Health Promotion Model for Culturally-Safe, Trauma-Informed Remote Virtual Delivery with Indigenous Northern Youth","Indigenous youth in remote communities in Northern Canada experience disproportionately high rates of STBBIs compared with other regions and creative interventions are desperately needed to curb this trend. SExT: Sex Education by Theatre is a theatre-based, culturally relevant, peer education participatory action research project that I developed as my doctoral thesis. Since 2018, in partnership with the Canadian Foundation for AIDS Research (CANFAR), SExT has toured nationally to regions most affected by HIV/AIDS and STBBI outbreaks, reaching over 6400 students across Ontario, Saskatchewan, and the Northwest Territories (NWT). In response to COVID-19, SExT partnered with Connected North, a cutting-edge program by Cisco and TakingITGlobal that provides an accessible digital platform through high definition, two-way TelePresence video technology. This study will engage Indigenous youth in Northern communities in a trauma-informed, culturally-safe, and virtual adaptation of the SExT intervention. Virtual workshops will involve interactive performances and theatre exercises led by SExT peer educators. Realist evaluation will unpack the mechanisms of how participatory remote online delivery of SExT works in particular contexts. Pre-post surveys with students and educators will assess self-reported changes in knowledge, attitudes, and intended behaviours. t-tests and ANOVA will determine pre-post changes, differences between virtual and live conditions (live data previously collected), and demographic differences. Focus groups will be held with students and data analyzed through an iterative process using thematic analysis. Findings will be used to improve the intervention model and scale-up. SExT's ongoing national touring activities and COVID-19 related pivot to the digital space provide an unprecedented possibility to explore the opportunities and challenges associated with virtual delivery of arts-based sexual health promotion in remote Indigenous contexts.",,-99,"York University (Toronto, Ontario)",71078.85,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Indigenous People,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P26706,486175,A population-based analysis of acute diverticulitis emergent presentation patterns and surgical interventions: A natural experiment during the COVID-19 pandemic,"Acute colonic diverticulitis is a common diagnosis in adult patients, resulting in frequent emergency department visits and hospital admissions. Patients with diverticulitis are often managed with antibiotics alone, however, remain at lifetime risk for recurrent episodes that may be complicated by bowel perforation requiring emergency surgery (colon resection) with possible stoma formation (colostomy). To avoid complications associated with emergency surgery, patients who are deemed high risk for recurrence are recommended to undergo a prophylactic scheduled colon resection. The COVID-19 pandemic has resulted in a large backlog and extended wait times for non-cancer scheduled surgeries. Patients are therefore at risk of recurrent attacks requiring emergency surgery while awaiting scheduled colon resection. It is hypothesized that the COVID-19 pandemic related delays in scheduled colon resections have resulted in more severe episodes of diverticulitis and increased rates of emergency surgery with stoma formation. I propose a large population-based study, inclusive of all adult residents of Ontario to (1) quantify the backlog of scheduled colon resections for diverticulitis in Ontario and (2) characterize disease severity and emergency surgical interventions in Ontario occurring during the COVID-19 period (Mar 2020-Dec 2022) compared to the pre-pandemic baseline (Jan 2017-Feb 2020) to better understand how the pandemic has impacted disease trajectory and resultant surgical management. This comprehensive analysis will inform provincial recovery strategies to address the surgical backlog in Ontario and allow for appropriate prioritization of scheduled colon resections for diverticulitis to mitigate potential complications resulting from delays in scheduled surgery.",,-99,University of Toronto,13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26709,459201,COVID-19 in the urban built environment (CUBE): Evaluating the use of environmental swabs for the detection and surveillance of SARS-CoV-2 in school and congregate settings,"Surveillance for SARS-CoV-2 in populations and the environment has been a critical component of our public health toolbox throughout the COVID-19 pandemic response. Ottawa pioneered the use of environmental surveillance, through wastewater signals, to predict COVID-19 disease burden in the community and inform the local public health response at a broad level. Building on previous work in hospitals, our study team addresses an important gap in surveillance: schools, childcare and long-term care settings. Most children and youth with COVID-19 will have few or no symptoms, yet they could still face considerable disruption to learning and potential hospitalization for their illness. Conversely, the risk of morbidity and mortality is highest in the older frail adult population. Testing for COVID-19 has been recommended to break chains of transmissions in classroom cohorts and congregate living settings. Yet testing students remains challenging because of difficulties in accessibility, acceptability of sampling methods, and the ability to screen low-risk students in schools serving communities with high rates of COVID-19. In long-term care, there is additional concern of waning immunity among staff and residents who were vaccinated more than six months ago, increasing residents' vulnerability to infection from asymptomatic or mildly symptomatic individuals. Our method of environmental sampling of floors could improve upon the spatial resolution of wastewater surveillance while focusing human testing only where it is needed. We will draw from vaccination rates to also provide insights into the SARS-CoV-2 environmental burden in a vaccinated population (such as high schools, long-term care), as testing criteria may evolve and no longer reflect infection prevalence, and at a finer spatial scale than conventional wastewater sampling.",,-99,University of Ottawa,393832.63,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease surveillance & mapping,2021 +P26712,471161,Addressing the impact of the COVID-19 pandemic on people who use drugs through health system innovation,"People Who Use Drugs (PWUD) are facing increasing threats to their health and well-being due to COVID-19, drug poisoning deaths, houselessness, and other conditions. There is an urgent need for PWUD-centered responses to these emerging health threats. Using sense-making methods, asset mapping, and partner roundtable discussions, this project will document PWUD priorities for health interventions, identify community strengths that will help to implement these interventions, and determine what other resources are needed for implementation. The project builds on a two decade partnership between PWUD, the Boyle Street Community Services organization, and academics in Edmonton, Alberta. We will use community-based participatory research principles, with PWUD as core team members and leaders on the project. We expect the project to help PWUD community members with health promotion and health literacy, bring evidence into practice in an underserved setting, and build community and organizational capacity for patient-oriented research.",,-99,"Boyle Street Community Services (Edmonton, AB)",149007.28,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2022 +P26714,448872,"Mental health in people at risk from COVID-19 due to a pre-existing medical condition: longitudinal study of risk factors, outcomes, and the role of vaccination","The COVID-19 pandemic has disrupted the lives of people in Canada and across the world due to its rapid spread, number of deaths, toll on health care systems, and devastating economic impact. In addition to fears of being infected or that friends and family members will be infected, there are fears that health care systems will not be able to provide necessary care, that isolation and movement restrictions will be long-lasting with a heavy toll on mental health; and that individual and societal resources will be insufficient. Serious mental health implications will likely extend beyond the acute outbreak period, particularly for vulnerable individuals with pre-existing medical conditions and elevated risk of medical complications or mortality from COVID-19. Many of these individuals are acutely afraid of infection and are under strict isolation protocols that will continue well beyond the period required for other people. Addressing mental health in vulnerable populations and providing effective responses, during COVID-19 and subsequently, requires understand patterns of symptoms and factors associated with them. Vaccination may play an important role. The Scleroderma Patient-centered Intervention Network (SPIN) is a collaboration of patients, researchers from 8 countries, and > 25 patient organizations from around the world. SPIN maintains an ongoing cohort (N > 2,000) of participants from 50 centres through which SPIN studies patient-prioritized problems and develops and tests interventions to address those problems. SPIN launched a separate COVID-19 cohort and enrolled over 800 people before closing enrolment on April 27, 2020. We continue to follow over 550 participants who complete monthly assessments. This is the only cohort in the world that has compared mental health in COVID-19 to pre-COVID-19 levels and followed participants across the pandemic with frequent assessments. It is critical that we continue to collect crucial data.",,-99,Lady Davis Institute for Medical Research (Mtl),138530.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26716,492850,"Improving Immunization Services and Health Outcomes for Children and Families in the Saskatchewan Health Authority - North, East, South, West, and Core Health Networks: A Community-Based Participatory Research Project","Immunization is a publicly funded public health strategy that has saved more lives than any other health service. With the impact of the COVID-19 pandemic and the Saskatchewan Health Authority immunization services returned to pre-pandemic levels, it is essential to explore the reasons why immunization rates have dropped, how immunization rates can be improved, and ways to improve immunization services. Context specific information is essential to plan services, quality improvement of programs, and better meet the needs of families in Saskatoon and surrounding area. The SHA is committed to truth and reconciliation and that includes fostering culturally safe care for Indigenous families to reduce access barriers and improve health outcomes. With these goals, examining the experiences of Indigenous families is essential to provide culturally safe child health clinics within the SHA. This study proposes to collect data through a survey and then apply the survey results to inform focus groups, and interviews with families and frontline workers, i.e., public health nurses, community program builders, and office administrative assistants to answer the following research questions: (1) what are the factors that support immunization for families with children 0-6 years of age in the Health Networks in and around Saskatoon, SK?; (2) What are the factors contributing to low immunization rates?; (3) How can immunization health services be modified and improved? To work in a good way with the community partner, the SHA, a community-based participatory research (CBPR) approach will be applied. A Research Advisory Committee has been formed with SHA leadership, engagement with the First Nations and Metis Health Services, and current recruitment of Indigenous Knowledge Keepers, and family partners. We are currently developing the study and data collection tools, plan to submit ethics in the next month and begin survey data collection once ethical approval is obtained.",,-99,University of Saskatchewan,1985.01,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26718,475159,"Informing an Equitable, Sustainable and Comprehensive Nursing Workforce Development, Support & Retention Strategy through Comparative Policy Analysis & Integrated Healthcare Workforce Planning","The COVID-19 pandemic has made it even harder for health care organizations to make sure they have enough nurses to look after their patients. Due these problems, many health care organizations in Canada and around the world no longer have enough nurses to provide the care their patients need. The goal of this study is to bring together different kinds of evidence to create a Nursing Strategy for Nova Scotia that will solve these problems and make sure we have enough nurses to provide the care Nova Scotians need. We will do this through three phases of activity: -In Phase 1, we will by (1) review scientific papers, government reports, and other evidence that has already been produced on this topic, (2) compare the ways Nova Scotia has managed and supported its nursing workforce with how four other health systems like Nova Scotia's have managed and supported theirs, and (3) based on what we learn in (1) and (2), make a list of different ways of managing and supporting the nursing workforce that could help make sure Nova Scotia has enough nurses to provide the care Nova Scotians need. -In Phase 2, we will host an online workshop with Nova Scotia nurse leaders and the different groups of people involved in training, managing, and supporting them in Nova Scotia (government, health authority, community partners, experts, patients and family advisors, nurses). During this workshop we will share what we learned in Phase 1 and work with these groups to decide which new or different ways of training, managing, or supporting nurses should be part of Nova Scotia's Nursing Strategy. -In Phase 3, based on all of the information we collect in Phases 1 and 2, we will present a Policy Brief to policy-makers in Nova Scotia telling them what should be included in a Nursing Strategy for Nova Scotia. Through these activities, we will offer in the leaders of Nova Scotia's health care system a plan for making sure the province has enough nurses to provide the care its people need.",,-99,Nova Scotia Health Authority (Halifax),109655.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Health Systems Research | Secondary impacts of disease, response & control measures",Health workforce | Indirect health impacts,2022 +P26719,479728,Hospital characteristics and Adverse event Rate Measurements (HARM) Evaluated over 21 years.,"An adverse event, a measure of patient safety defined as an unintended consequence of healthcare that leads to patient harm, is experienced by approximately 9% of hospitalized patients during a hospital stay. Adverse events, which include infections arising in hospital, reactions to drugs, and complications from medical procedures, can increase both the hospital length of stay and the risk of a an in-hospital death. Adverse events result in harm to the individual patient and considerable costs to the healthcare system. Across Canada, substantial expenditures on patient safety have been justified by the goals of reducing healthcare-associated harm and its associated cost, but the available evidence suggests that these programs have not improved overall safety; adverse event rates per hospital stay are unchanged over the past four decades. There is a need for research aimed at identifying better targets for healthcare safety programs. The proposed research will meet that need, using records from the Canadian Institute for Health Information of all in-hospital adverse events occurring between 2002-22 in adults at eligible Canadian hospitals. Three separate objectives will be addressed as part of the overarching objective of describing adverse events affecting adult hospitalized patients in Canada: [1] To estimate rates over-time from 2002-2022, overall and for those receiving ICU, surgical, medical, and obstetric care . [2] To evaluate the effects of factors that put the health system under stress - factors related to epidemic and pandemic conditions (e.g., influenza, COVID-19), time and day of admission, and how close a hospital is to being full. [3] To evaluate effects of factors that may make a patient more susceptible to adverse events. We will investigate socioeconomic status and physiologic factors such has age and co- existing illnesses, and will also assess whether these factors have stronger effects at times the healthcare system is under stress",,-99,University Health Network (Toronto),336403.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2023 +P26720,448951,Optimizing a Cost-efficient and Scalable COVID-19 Early Warning System at a Strategic Canadian Land Entry Point,"Windsor-Essex sits at one of the busiest border crossings between the USA and Canada and is located at the heart of intensive year-round agricultural operations with a high concentration of migrant workers who arrive seasonally from Mexico, Central America, and the Caribbean. Transmission resulting from travel makes this region particularly susceptible to the introduction of novel coronavirus variants. In Windsor-Essex, students at the University of Windsor and St. Clair College are highly embedded into this community, with most living and working off-campus. The asymptomatic young population is of particular concern for the spread of the variants. This proposal aims to optimize a surveillance system, combining wastewater testing and a rapid saliva-based RNA-extraction-free testing program. The combined use of these COVID-19 detection methods enables the early surveillance and rapid detection of COVID-19 to prevent the spread of disease. Beginning with our students on the University of Windsor and St. Clair College campuses, we will provide screening for a population whose future was most impacted by this pandemic. They are also a keen and educated population who will provide valuable input into the process. Our team also includes an industrial partner specialized in diagnostic equipment design and manufacturing, which will help in automation and cost reduction, standard compliance of the testing methods. We also partnered with WE-SPARK Health Institute to ensure the proper digital record of COVID status and efficient knowledge translation. In summary, this proposal will begin the process of enabling a safe return to the campus for our young generation, which is critical for a sustainable society. Collectively, this work will move the science and technology forward to rapidly detect COVID-19 and begin monitoring for COVID-19 in a strategic Canadian land entry point. This multidisciplinary team in Windsor-Essex is uniquely positioned to tackle these goals.",,-99,University of Windsor (Ontario),397222.41,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified | Not applicable,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Epidemiological studies | Pathogen: natural history, transmission and diagnostics",Disease surveillance & mapping | Diagnostics,2021 +P26722,450298,Building capacity for systems biology analysis of adverse events following COVID-19 vaccination in low- and middle-income countries,"The development of safe and effective vaccines is helping to control COVID-19. Though benefits of vaccination outweigh risks, rare, serious adverse events have been reported after vaccine introduction in North America and Europe. One example is thrombosis with thrombocytopenia syndrome (TTS) associated with COVID-19 vaccines produced by AstraZeneca and Janssen. Patients develop blood clots, low platelets and bleeding that can be fatal. Safety concerns may slow vaccine uptake, particularly in low- and middle-income countries (LMICs) where these vaccines may be the only option available. It is important to understand what causes serious adverse events like TTS and who might be at risk to ensure the safety of COVID-19 vaccines. Systems biology involves detailed analysis of DNA, RNA, proteins and other molecules. Patterns in these molecules can be compared between patients with adverse events and healthy people to provide information into how vaccination may cause adverse events. A challenge to applying system biology technologies to study very rare adverse events like TTS (which occurs in 1-2 per 100,000 people) is identifying enough patients from different backgrounds with the condition. This study aims to address this gap by building partnerships with physicians and public health in LMICs to identify and recruit patients with rare adverse events, collect data and samples. This will allow us to apply systems biology to learn about the causes of adverse events from patients around the world. This research will help to make vaccines even safer in the future. The study lead, Dr. Top is a physician and expert in vaccine safety who co-leads an international network of experts in vaccine safety and systems biology. She will work with the Brighton Collaboration, a global organization focused on vaccine safety evaluation on this project. Dr. Top's expertise, experience, and collaborations with systems biology experts will ensure the success of this project.",,-99,Dalhousie University (Nova Scotia),324130.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation",Adverse events associated with immunization,2021 +P26725,473352,Designing public vaccine procurement contracts to secure a socially optimal level of vaccination,"The proposed research seeks to supply guidelines for public vaccine procurement contracts that incentivize vaccine manufacturers' production capacity building and align the interests of government vaccine buyers and vaccine manufacturers to increase the availability of vaccines in any possible future outbreaks. The outcomes of this research aim to support building Canada's advanced vaccine production capabilities. The low vaccine coverage rate, below the socially optimal level of vaccination, has been a severe concern internationally. For example, Canada recently reported shortages of the new shingles vaccine, hepatitis A and B shots, and rabies vaccine. It was also reported that manufacturers of COVID-19 vaccines established inadequate capacity before regulatory approval. Reasons for the insufficient capacity include the risks in vaccine development, regulatory approval, high demand uncertainty, and manufacturers' fear of losing the capacity-building cost. Government agencies play a crucial role as buyers of vaccines from private vaccine manufacturers. However, there is a conflict of interest between government buyers and vaccine manufacturers in the procurement contracts. Government buyers usually bargain down the procurement price to control their financial expenditure, which hurts the manufacturers' profit margin and results in insufficient capacity building. Although it has long been argued that economic incentive contracts between government buyers and vaccine manufacturers should be implemented, many governments, including Canada, have not carried out necessary sweeping reforms to vaccine procurement contracts. The proposed research seeks to shed light on the optimal government vaccine procurement contracts in an infectious disease outbreak. The proposed research aims to find contract terms that align the objectives of the two players and achieve the socially optimal level of vaccination.",,-99,"York University (Toronto, Ontario)",76662.06,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen | Other,,,,,,,,,COVID-19 | Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Health Systems Research","Vaccine logistics and supply chains and distribution strategies | Medicines, vaccines & other technologies",2022 +P26727,479161,Telehealth for Emergency-Community Continuity of Care Connectivity via Home Blood Pressure Telemonitoring (TEC4HOME-BP),"Hypertension (high blood pressure) is the leading cause of death and disability globally and is the most common reason for physician and emergency department (ED) visits in Canada. We are now facing the lowest rates of hypertension treatment and management in more than a decade. Currently, about 1 in 5 Canadian adults have hypertension, of which, about 1 in 3 people do not have their blood pressure (BP) under control. Lowering BP levels by a small amount, can dramatically reduce risk of heart attacks by 20%, stroke by 35%, and heart failure by 40%. Emergency Departments (ED) are a convenient locations to screen for hypertension as everyone gets their BP checked. However, many care providers do not know that high BP in the ED can predict those who actually have a diagnosis of hypertension or cardiovascular disease. Although guidelines recommend close follow up for these individuals, in reality follow up and monitoring of BP after discharge from the ED is inconsistent and fragmented. Hypertension is one of the chronic diseases that can be managed effectively at home, through use of digital health technology. During the global COVID-19 pandemic, there was a significant increase in the use of virtual health. This represents an opportunity to use digital health tools for home BP telemonitoring, and integration in hypertension clinical practice. Use of digital health tools can significantly improve self-management, medication adherence, patient engagement, and BP control. Our study is to better understand if digital health tools, including home BP telemonitoring combined with pharmacist led adjustment in medications can improve BP control compared to usual care in people who have high BP in the ED. The study's results could also streamline how patients with hypertension transition through ED, reduce the length of their stay in hospital and improve their overall safety and quality of care.",,-99,Vancouver Coastal Health Research Institute,703183.7,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26728,444613,Acting together on team resilience at work in oncology to optimize the capacity to cope with difficult situations: a multiple case study according to the realistic evaluation in the Quebec oncology network,"Cancer care teams face difficult situations on a daily basis: announcement of a cancer diagnosis and bad news about the progression of the disease, distress of patients and their loved ones, scarcity of resources. These situations are amplified by COVID-19. Teams are at risk of compassion fatigue, burnout and being at the end of their resources. These risks affect team functioning, health and quality of life at work; and ultimately impact the provision of care. Although there are promising interventions, research to support resilience and assess its effects among specialized cancer teams is almost non-existent. The study aims to better understand how to intervene to support the resilience of teams working with people affected by cancer. To be useful and feasible, the intervention is based on a close partnership approach with professionals from clinical teams and members of management teams so that they can provide quality and safe care. We will analyze the facilitators and barriers to resilience and evaluate the effects of the intervention using interviews, observations and questionnaires. Four healthcare institutions in Quebec with several cancer teams have committed to participating. The study will provide new data on best practices to better support team resilience at work in a specialized care sector. The local support and detailed description of the intervention, its mechanisms of action and its effects are part of supporting decision-making to optimize team resilience capacity. The results may inspire other initiatives in Quebec, elsewhere in Canada and in other countries where the well-being of care teams is an essential condition for the provision of care during and after COVID-19.",,-99,Université de Sherbrooke,461891.01,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2021 +P26729,449305,Evolution of adherence to effective prevention measures against COVID-19 by young people in secondary school - the influence of school events linked to the pandemic,"The project seeks to verify whether since the first wave and its period of confinement, the preventive practices put in place by adolescents against COVID-19 have varied according to their level of exposure to school events linked to the pandemic. Last March, young people saw their lives turned upside down due to the pandemic, having to interrupt their studies and finish the year virtually. Having largely adhered to preventive measures during this period, they have since returned to schools, highlighting the need to monitor the evolution of their adherence to preventive measures and its determinants in this group which could become one of the important vectors of the disease. The project is part of the COMPASS-Québec research platform launched in 2016-17. It welcomes a cohort of more than 4,000 young people from the first to the fourth year of secondary school who responded to an online questionnaire asking about their health, their knowledge, opinions and their behaviors in May-June 2020. This m The same questionnaire will be distributed electronically one year later (spring 2021) to students from the 29 participating schools. Data surrounding school events linked to the pandemic (e.g.: switching classes to virtual mode) will be collected during this interval in collaboration with the educational establishments with which the researchers have established over the years, with the help of management regional public health authorities, a partnership to the benefit of students. Effective preventive measures (e.g.: hand washing, wearing a mask) will have been evaluated at both measurement points. The results of this study will improve our understanding of the impacts of the pandemic on the behavior of young people and its determinants.",,-99,Université Laval,13459.8,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2020 +P26735,443920,B cell-intrinsic insulin resistance as a mechanism of obesity-linked immune dysfunction,"Obesity predisposes to insulin resistance (IR), a state where the body responds poorly to the metabolic hormone, insulin. Obesity/IR pose a significant global health threat, as the accompanying inflammatory changes in obese individuals sprout serious health complications such as cardiovascular disease and type 2 diabetes. In addition, obesity and IR undermine immune function and are associated with significantly elevated risks of severe infections and mortality, as exemplified by the H1N1 influenza pandemic (2009) and the current COVID19 pandemic. Complex physiological changes and immune-endocrine interactions are thought to contribute to the observed immune defects, although the precise mechanisms are not well understood. Following the clues that insulin resistance can occur in a manner that is intrinsic to immune cells, and that insulin receptor on immune cells modulate their metabolism and function, we hypothesize that insulin resistance in immune cells, such as B cells, is a major link between obesity and an impaired anti-viral response, leading to increased disease severity and associated mortality. In this study, we will explore the role of the insulin receptor by deleting it from B cells, a type of white blood cells that mediate protective immune responses by secreting antibodies. We will also utilize a high fat diet-fed obese mouse model to study the adverse effects of obesity and IR on B cell function during severe respiratory infections with H1N1 influenza. Importantly, we will determine whether the severity of these infections can be improved with drugs used to treat diabetes. Findings from this study will provide new and important insights into how obesity impacts B cell function, and lay a foundation for the development of therapeutic/vaccination strategies to better cater to the obese, insulin resistant population during current and future viral pandemics.",,-99,University of Alberta,659409.86,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P26736,443344,COVID-19 Variant Network - Point of Care Heart-Lung Imaging for Patients Presenting with COVID-19 Symptoms: Artificial Intelligence Precision Modeling for Prediction of Outcomes,"The global COVID-19 pandemic has placed a huge burden on health care systems and upended our way of life. It is caused by the highly infectious virus, SARS-CoV-2. Rapid and accurate testing for viral infection is needed to prevent spread of disease in hospitals and the community so that infected people can be identified early and treated effectively. EARLY COVID-19 symptoms are similar to many other respiratory viruses, like the flu and common cold, making it hard to identify in sick patients.The current approach to SARS-CoV-2 testing can be inaccurate and slow to return results. Improving diagnosis of COVID-19 will be even more important as flu season approaches. Our experience to date in treating patients with COVID-19 symptoms has shown that ultrasound imaging of the heart and lung may help identify positive cases earlier. Ultrasound is fast and safe. It can be performed at the bedside [point of care ultrasound (POCUS)] when patients first enter the hospital, by any physician with remote support from POCUS experts. In this study, we will test if adding heart and lung ultrasound images to existing clinical and laboratory tests can improve the accuracy and speed of COVID-19 diagnosis. A total of 16 hospitals across British Columbia and Ontario will participate in this study, and we will analyze this large data set using artificial intelligence (AI). Our team has already developed a platform to share ultrasound data and applied AI to study other heart diseases, so we are ready to rapidly apply this approach to COVID-19. If POCUS is effective it would allow earlier treatment and isolation of positive cases, reducing exposure of frontline health care workers and the public to the virus, improving both patient care and the distribution of health resources like personal protective equipment, intensive care beds and ventilators. Because POCUS-based COVID-19 diagnosis can be performed remotely it could also be applied in long term care facilities and in rural areas.",,-99,University of British Columbia,78392.55,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2021 +P26738,484612,"How telemedicine affected the comprehensiveness, continuity, technical quality, and equity of care","Poor access to Canadian primary care has been an ongoing challenge that is exacerbated by the COVID-19 pandemic. Although telemedicine may improve access, its overall impact on health system remains dubious. The College of Family Physicians of Canada (CFPC) would like to assess the impact of this technology while leveraging the evaluation effort to simultaneously inform its long-term national health system database initiative. This fellowship therefore aims to: 1) identify primary care performance indicators on comprehensiveness and continuity of care that can simultaneously support telemedicine evaluation, CFPC's national database development, and CFPC's Patient Medical Home initiative; 2) examine the impact of telemedicine on the comprehensiveness, continuity, technical quality, and equity of care; and 3) generate policy- and education-related recommendations for CFPC regarding telemedicine. This fellowship will first conduct scoping review of theoretically and practically useful indicators on comprehensiveness and continuity of care. I will then use a quasi-experimental method to identify the impact of telemedicine on the comprehensiveness, continuity, technical quality, and equity of care. I will then derive the appropriate policy- and education-related recommendations based on the findings. The fellowship offers opportunity to interact with various members and organizations embedded in the policymaking, education, advocacy, and academic realms. The diverse range of perspectives on the ideas, interests, institutions, and positions will help me cultivate my competencies in understanding and comparing health systems and the policy making process; dialogue and negotiation; and change management and implementation.",,-99,"The College of Family Physicians of Canada (Mississauga, Ont.)",79786.07,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2023 +P26740,486092,"Alexa, is my cough normal? Refinement of a Machine Learning Algorithm Using Capsaicin Invoked Cough Signals for Cough Categorization","Respiratory diseases cause about 20% of deaths worldwide and are often under-diagnosed (Jose´ et al., 2014). Under-diagnosis implicates many health consequences such as increased respiratory complications and mortality, necessitating a higher rate of detection. Coughing is an important symptom of respiratory diseases and certain characteristics of coughs can indicate the presence of a respiratory condition. Previous studies have used Machine Learning Algorithms (MLA) and Artificial Intelligence to detect voice disorders and COVID-19 coughs. Given this success with MLA detection, training an MLA to detect characteristics of cough sounds can aid in diagnosis of respiratory conditions. To train this MLA, healthy voluntary and involuntary cough sounds will be collected. Appropriate refinement of an MLA requires high quality and appropriately diverse inputs to ensure accurate outputs and to avoid exacerbation of existing health disparities that can affect patient health outcomes. Appropriate data collection, pre-processing, and batch-normalization of data are vital processes to increase the accuracy and quality of MLA outputs. Thus, the obtained diverse cough sound data will be pre-processed for effective batch-normalization to ensure appropriateness and quality of the output. Involuntary coughs will be invoked by administering capsaicin, the pungent element of hot peppers. Capsaicin induces the cough reflex comparable to initiating a real cough. Refining the MLA with these invoked healthy coughs will ensure a more accurate distinction between healthy and disease related coughs. With the availability of an accessible tool, respiratory conditions may be easily screened in a variety of applications including in primary health, monitoring patient progress, and Telehealth use.",,-99,University of Alberta,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2022 +P26744,432316,Tracking the Prevalence and Incidence of Modifiable Suicide Risk Factors During the COVID-19 Pandemic to Inform Targeted Suicide Prevention in British Columbia,"Half of Canadians report worsened mental health since the COVID-19 pandemic began disrupting our lives this Spring. These impacts, combined with rising prevalence of known suicide risk factors such as unemployment and financial hardship, social isolation, alcohol and substance use, relationship strain and domestic violence, have raised concerns that of rising suicide risk in the Canadian population. Canada loses 3,800 to 4,500 lives to suicide each year. Suicide death and bereavement confer long-term psychological and social risk to families and communities. A small increase in suicide rate can thus result not only in excess loss of life, above and beyond the direct impacts of the pandemic, but also confer long-term vulnerability in our communities. To support efforts to increase targeting of mental health resources to specific demographics, regions, and groups, this study aims to characterize the specific mental health and related cognitive impacts of the COVID-19 pandemic responses to inform evidence-based policy that can mitigate secondary suicide risk. We will recruit 5,000 community adults, with balanced representation of across age groups (10-year age bands from 19-29 to 70-79), sexes (male, female), geographic regions, and household incomes. Surveys will focus on Canadians' emotional, physical, and cognitive wellbeing across distinct phases of the pandemic (Summer 2020; Fall 2020; Winter 2021). In addition, we will co-create supplemental surveys to assess the mental health vulnerabilities, resilience, and lived experiences with three potentially vulnerable groups: frontline mental health workers, Indigenous peoples, and people living in rural or remote areas. Supplemental surveys will be developed with knowledge users and community members so they are relevant and responsive to community needs. Our results can inform mental health strategies by identifying where, with whom, and what kind of intervention is needed to effectively reduce suicide risk.",,-99,University of Victoria (British Columbia),117929.75,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting,Indigenous People,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26746,473340,Advancing Health System Leadership Capacity for Psychological Health and Organizational Resilience during the COVID-19 Pandemic and Beyond,"Health leaders' action during a crisis, such as COVID-19, serves to guide and support others' actions, during unpredictable health service demands. As the COVID-19 crisis continues the mental wellbeing of leaders and nurses remains strained, and made worse by nurse absenteeism, turnover, and burnout. There is no known research in Canada addressing leader and nurses' mental health and wellbeing affecting the hospital's ability to care for patients during a health crisis, post-crisis, and future health crises. This information is needed to advance post-crisis leadership strategies for health leaders to better address their own and nurses' psychological health and wellbeing while simultaneously responding to COVID-19 patients, and a backlog of patients requiring surgery and treatments. Health system leaders have a responsibility to preserve the wellbeing of nurses and ensure quality healthcare while retaining compassionate engaged and experienced nurses. In this 3-year study, our objectives include: 1) examine how leaders respond to and adapt their leadership practices in response to the COVID-19 pandemic; 2) investigate nurses perceptions, clinical challenges, work conditions and their mental health; 3) examine how leaders can promote their own and nurses' mental health to mitigate strain and burnout; 4) integrate data from objectives 1,2 and 3 to determine how leaders can promote mental health in men, women, and non-binary individuals and decrease negative outcomes to ensure hospital performance; 5) identify recommendations that build leader and nurses' mental health to ensure a healthy and diverse workforce within hospitals during the ongoing pandemic, post-crisis, and future crises. The accumulated knowledge will be shared with leaders in health services, researchers, and policy makers across Canada so that promising leadership strategies and practices can be used to improve and advance health leadership and hospital performance.",,-99,University of Manitoba,344979.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance | Health workforce,2022 +P26754,432597,"""J'accompagne COVID-19"": un projet de recherche action participative mettant à l'épreuve une modalité de soutien virtuelle innovante développée selon le modèle des communautés compatissantes afin de comprendre et prévenir le deuil compliqué en contexte de pandémie","Les mesures de santé publique afin d'enrayer la propagation de la COVID-19 ont bouleversé de manière tragique l'accompagnement des personnes en fin de vie ainsi que le processus de deuil de leurs proches. À ce jour, les particularités du deuil en contexte de pandémie n'ont été documentés par aucune étude. Toutefois, plusieurs écrits permettent de conclure que ce contexte implique de nombreux facteurs susceptibles de générer une augmentation des deuils compliqués. En parallèle, les mesures de confinement et de distanciation physique bouleversent les modalités de soutien psychologique destinées aux endeuillés. Les principales organisations communautaires offrant du soutien de groupe ont dû suspendre leurs activités. Les services professionnels de psychothérapie individuelle peuvent s'offrir de manière virtuelle, mais posent un défi certain en termes d'accessibilité et d'équité compte tenu des coûts qu'ils engendrent pour les individus endeuillés dont la sécurité d'emploi est souvent affectée. En avril 2020, notre équipe a bénéficié d'une subvention de démarrage afin de mettre sur pied le projet << J'accompagne >>; un projet de recherche action participative développé selon l'approche des communautés compatissantes. Ces fonds nous ont permis de recueillir des données empiriques par l'entremise d'entretiens qualitatifs en profondeur auprès de 13 participants endeuillés des suites de la COVID-19 et ainsi de mieux comprendre leurs besoins de soutien. Dans le cadre de la présente demande, nous souhaitons : poursuivre et approfondir notre compréhension du deuil en contexte de pandémie en augmentant la taille de notre échantillon, ajouter un volet longitudinal en documentant l'évolution du processus de deuil de ces participants afin de cerner les facteurs susceptibles de contribuer aux complications possibles du deuil et documenter l'efficacité d'une modalité de soutien virtuelle alternative et accessible destinées aux personnes endeuillées dans le contexte de la pandémie.",,-99,Université du Québec à Montréal,55389.35,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health | Innovation,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P26758,459213,Compounding Disadvantage: Impact of COVID-19 among Immigrants living with Cancers and with Mental Health & Addictions Disorders in Ontario,"The COVID-19 pandemic has jeopardized Canadians' physical and mental health. Immigrants in Canada bear a disproportionate burden of the pandemic. Research shows that more than half of COVID-19 cases in Ontario are among immigrants even though they only comprise a quarter of the population. There are more COVID-19 cases in areas where residents are recent immigrants, living in poverty and unemployed. In addition, immigrants with chronic illnesses also have a higher risk of getting infected and becoming very sick with COVID-19. Among people with chronic illness, those living with cancer or mental health and addiction (MH&A) are also at a higher risk of COVID-19 and worse outcomes. Cancers and cancer treatments weaken the body's immune system, and people with pre-existing MH&A problems experience barriers to health services. Immigrants who have either of these conditions may be at especially high risk of contracting and/or dying from COVID-19. However, there is a lack of research on the risk for these affected groups. Understanding the impact of COVID-19 on immigrants living with these high-risk conditions is critical to develop effective responses to the pandemic. Our study aims to determine 1) if immigrants with a) active cancers or b) MH&A are at higher risk/likelihood of COVID-19 vaccination, diagnosis, hospitalizations, ICU admissions and mortality than non-immigrants with the same conditions, and immigrants and non-immigrants without the same conditions; 2) the role that other sociodemographic and healthcare-related variables play in COVID-19 diagnosis for immigrants with a) active cancers and b) MH&A; and 3) which knowledge translation strategies can promote access to health services during current and future crisis, through Think Tanks with affected communities, service providers and decision makers. Our research team consists of well-recognized researchers and knowledge users in the fields of mental health, cancer, health equity, and primary care.",,-99,Toronto Metropolitan University,336443.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Epidemiological studies | Policies for public health, disease control & community resilience | Health Systems Research",Disease susceptibility | Disease surveillance & mapping | Approaches to public health interventions | Health service delivery,2021 +P26759,480719,The impact of the COVID-19 pandemic on rehabilitation delivery and outcomes in the province of Quebec.,"This study aims to estimate the impact of the pandemic on the delivery of rehabilitation care to stroke users having contracted or not COVID-19 by (1) comparing their healthcare indicators and rehabilitation outcomes and (2) identifying factors of influence. We hypothesized that rehabilitation outcomes would be negatively affected in all stroke users during the pandemic due to operational changes in the provision of rehabilitation services, even more so for those who contracted COVID-19 because of their concomitant health condition.",,-99,McGill University,1107.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26761,456729,Treatment of Sleep Difficulties Associated with Atypical and Disorganized Work Schedules in Healthcare Workers,"Healthcare workers and especially those working on shifts, are at risk of developing sleep disturbances, anxiety and depression. This is especially true during the COVID-19 pandemic crisis since they are required on the frontlines and are consistently working under duress. As a result, many are quitting their positions or are on sick leave even though Canadians still need them to be alert and productive at work. Our project proposes to test the efficacy of a new psychological and behavioural intervention to improve sleep and fight anxiety and depression in healthcare workers on shifts. The intervention proposed in the project is scientifically based. It will be delivered via psychologists with an adapted digital platform to facilitate treatment access and overcome challenges of lack of time in this population. The intervention will be tested in the CIUSSS du Nord-de-l'Île-de-Montréal and the CIUSSS de la Capitale Nationale. The scientific work will be sustained through a concerted approach of two local knowledge appropriation committees associated with each CIUSSS. Each committee will include up to 10 local experts (management and human resources, union representatives, workers on atypical schedules/knowledge users, and others) who will facilitate local deployment of the study. Dynamic interactions between the researchers and the local knowledge appropriation committees will allow scientific efforts to be focused on the development of solutions rapidly applicable to the healthcare workplace. Importantly, our study will also identify the individual and environmental factors to target in order to prevent sleep and mental health difficulties in healthcare workers on atypical schedules. The context of the COVID-19 pandemic we are facing today gives Canada the opportunity to provide efficient solutions to improve sleep and mental health in healthcare workers and increase their resilience in this time of crisis.",,-99,CERVO Brain Research Center (Québec),78858.79,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26765,444335,Online Public Health Nurse-Delivered 1-Day Cognitive Behavioural Therapy-Based Workshops for Postpartum Depression,"Postpartum depression (PPD) affects up to 1 in 5 mothers and is associated with costs of $150,000 per case over the lifespan. The COVID-19 pandemic has fundamentally altered the ways in which mothers access postpartum mental health care, with most now preferring to receive treatment online or by telephone. Under normal conditions, just 1 in 10 mothers with PPD get evidence-based treatment, a situation that has worsened substantially during COVID-19. As a result, innovative interventions capable of overcoming barriers and reaching large numbers of women safely are urgently needed to reduce the adverse effects of PPD on mothers, their families, the healthcare system, and society as a whole. The purpose of this study is to test the effectiveness of a Public Health Nurse-Delivered Online 1-Day CBT-Based Workshop for PPD. We will conduct an Ontario-wide randomized controlled trial where 406 women will be recruited to receive either the Nurse-Delivered Online Workshop plus treatment as usual from their healthcare providers (treatment group), or treatment as usual plus three online information sessions (control group). We will compare the effect of the Public Health Nurse-Delivered Online 1-Day Workshop on levels of maternal depression, anxiety, and parenting stress, their relationship with their partners and infants, as well as the behaviour of their offspring in the treatment and control groups at three, six, and twelve months. We will also assess the cost-effectiveness of the intervention. Only treatments that are safe and that can be rolled out on a large scale can have a significant impact on PPD at the population level. To achieve this, a shift is needed toward treatments that can reach large numbers of mothers safely and efficiently. Public Health Nurse-Delivered Online 1-Day CBT-Based Workshops reduce many of the barriers to treatment that currently exist, and can help women and families both in Canada and around the world during the pandemic and beyond.",,-99,McMaster University,528743.54,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26766,438122,Online Public Health Nurse-Delivered 1-Day Cognitive Behavioural Therapy-Based Workshops for Postpartum Depression,"Postpartum depression (PPD) affects up to 1 in 5 mothers and is associated with costs of $150,000 per case over the lifespan. The ongoing COVID-19 pandemic has and will continue to fundamentally alter the ways in which mothers access postpartum mental health care. Under normal conditions, just 1 in 10 women with PPD get evidence-based treatment, a situation that has worsened substantially during COVID-19. As a result, innovative interventions capable of overcoming barriers and reaching large numbers of women safely are urgently needed to reduce the adverse effects of PPD on mothers, their families, the healthcare system, and society as a whole. The purpose of this study is to test the effectiveness of a Public Health Nurse-Delivered Online 1-Day CBT-Based Workshop for PPD. We will conduct a Canada-wide randomized controlled trial where 376 women will be recruited to receive either the Nurse-Delivered Online Workshop plus treatment as usual from their healthcare providers (treatment group), or treatment as usual plus an online informational session (control group). We will compare the effect of the Public Health Nurse-Delivered Online 1-Day Workshop on levels of maternal depression, anxiety, and parenting stress, their relationship with their partners and infants, as well as emotional and behavioural problems in their older children in the treatment and control groups at three and six months. We will also assess the cost-effectiveness of the intervention. Only treatments that are safe and that can be rolled out on a large scale can have a significant positive impact on PPD at the population level. To achieve this, a shift is needed toward treatments that can reach large numbers of mothers safely and efficiently. Public Health Nurse-Delivered Online 1-Day CBT-Based Workshops reduce many of the barriers to treatment that currently exist, and can help women and families both in Canada and around the world during the pandemic and beyond.",,-99,McMaster University,74711.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26769,469286,"Design, synthesis and testing of oxidatively robust inhibitors for cysteine proteases in SARS2 virus and poliovirus","According to Johns Hopkins University data, as of August 2022, COVID caused by the Severe Acute Respiratory Syndrome 2 (SARS2) virus has infected 589 million worldwide (4.14 million in Canada) and caused 6.43 million deaths (43,440 in Canada). Vaccines and health measures have helped contain infections, but many still become sick, and elderly or immunocompromised individuals are at risk for severe disease. Antiviral treatment is approved with orally active Paxlovid, which is a combination of nirmatrelvir that prevents viral replication and ritonavir that inhibits its metabolism. Unfortunately, ritonavir also inhibits metabolism of many other drugs, making correct dosages unclear. This is especially true for at risk populations that may be medicated for other conditions, such as cholesterol reduction by statins. Ideally, only a single drug that blocks viral proliferation with greater resistance to human metabolism would be administered to avoid undesired side effects with other medications. Nirmatrelvir and related antivirals (eg GC376) target an enzyme essential for viral replication, namely the 3CL protease that cuts a large protein initially generated into pieces used to make new virus. Human metabolism of nirmatrelvir occurs mainly in intestine and liver through oxidation by cytochrome P450 3A4. This enzyme metabolizes about 50% of all medicines and is blocked by ritonavir. Interestingly, some antivirals that inhibit the key protease of coronaviruses such as SARS2 also block the process in poliovirus (a picornavirus). Although ~92% of the population is immunized against polio, there are rare disease outbreaks such as one in 2022 in New York. We propose to make new viral protease inhibitors that are longer-lived in the body, can stop SARS2 replication and also block poliovirus in infected individuals. This work will provide antiviral drugs that can be given without ritonavir, are resistant to human metabolism and will suppress the virus in infected individuals.",,-99,University of Alberta,574735.47,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P26772,449503,Pandemic and access to food resources in Montreal: what impacts on vulnerable populations experiencing food insecurity?,"Issue: A public health issue, food insecurity results from an economic situation that does not allow individuals to have adequate income to eat enough. Before the pandemic, 12% of Montreal households were experiencing food insecurity. The COVID-19 health crisis, leading thousands of Quebecers into financial instability, increased the prevalence of food insecurity to 26% in April 2020. It also had significant consequences on food practices, the local food environment and the services of community food organizations, while the use of these organizations is one of the strategies used in situations of food insecurity. Objective: Understand how accessibility to community food organizations in the local environment influences the ability of low-income households to feed themselves before and since the application of health measures related to COVID-19. Methodology: 'Life story' type interviews (duration: 60 minutes) with representatives of 24 low-income households in 4 Montreal neighbourhoods (n=6 / territory), presenting diverse portraits in access to community food organizations. Contributions: This study will contribute to the knowledge of the impact of the economic blockage on a segment of the population affected by food insecurity 12 months after the health crisis. The results will be used to improve public health interventions by the Montreal Regional Public Health Department and other authorities, to promote access to and food supply for vulnerable people on the Island of Montreal.",,-99,Université de Montréal,13459.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P26774,486047,"Effects of Vinyasa Yoga and High Intensity Interval Training on Symptoms of Anxiety, Depression, and COVID-related Stress","Many individuals have persistent mental health issues as a result of the COVID-19 pandemic, including increased depression, anxiety and stress, in particular COVID-related stress. Exercise (e.g., yoga), in combination with controlled breathing, has shown promising results for deceasing levels of stress, depression, and anxiety. The present study aims to expand on past research and assess whether different forms of exercise will have an influence on levels of anxiety, depression, and COVID-related stress. Participants must not be currently active (i.e., not participating in more than 150 minutes of moderate intensity exercise per week) or practicing yoga of any kind. The participants will then be randomly assigned to one of three exercise conditions: (1) Vinyasa yoga, (2) high intensity interval training (HIIT), or (3) stretching. Each condition will consist of 30-minute sessions, three times per week, for eight weeks. I hypothesize that both Vinyasa yoga and HIIT will positively impact symptoms of anxiety, depression, and COVID-related stress, when compared to the stretching control. However, I also hypothesize that Vinyasa yoga will have the strongest impact on anxiety, depression, and COVID-related stress symptoms since it combines both flow movement exercise and controlled breathing. Given the nature of the psychological impact of pandemics on mental health, assessing the relationship between anxiety, depression, and COVID-related stress symptoms and Vinyasa yoga and HIIT may provide support for these exercises as efficient interventions.",,-99,University of Regina (Saskatchewan),13021.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26775,442968,Covid-19 and infodemic: information practices of groups in situations of vulnerability to COVID-19 in Quebec in the context of a pandemic.,"The historic measures put in place to protect the population from COVID-19 have disrupted the daily lives of Quebec residents, as well as those around the world. The pandemic has been accompanied by a continuous flow of information to the point that the WHO uses the term ""infodemic"" to describe an information overload. This proliferation of information accentuated by social media can have harmful repercussions for some people. The excess information can cause fear, anxiety, generate distrust of health authorities, lead to dangerous practices that can lead to deaths, or even non-compliance with preventive practices. Information practices are strongly influenced by socio-economic level, level of education, cultural origin or even place of residence. Thus, messages from public health authorities do not reach certain groups in situations of vulnerability to COVID-19 such as seniors (60 years and older), young adults (18-25 years), members of cultural communities and members of Indigenous communities living in urban areas. This is why it is important to identify the information practices of these different groups. The results will help guide the communication activities of public health authorities to better adapt to the needs of groups in situations of vulnerability to COVID-19, thus reaching them more equitably and encouraging adherence to the recommended measures.",,-99,Institut national de santé publique du Québec,116126.5,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Communication,2020 +P26779,432537,Traumatic stress and Mental Health Impacts of the COVID-19 Pandemic on Front-Line Workers in Homeless Services,"Lay Abstract: This proposal addresses the mental health impacts of the COVID-19 pandemic on frontline workers in the homeless sector. Prior to the COVID-19 pandemic outbreak, our research reported high levels of direct traumatic stress among frontline workers. In five previous studies, we surveyed frontline workers in homeless services, in Calgary, Edmonton, AB, and Saint John, NB. Results showed consistently high rates of traumatic stress across all locations, exacerbated by lack of training, inadequate preparation for responses in a pandemic and a perceived lack of physical and psychological safety that could potentiate further primary traumatic stress. Given the sudden and protracted impact of the COVID-19 virus and the systemic challenges faced in the social services, it is critical to examine how these experiences are impacting frontline workers' mental health and well-being. The overall goal of this research is to document the extent to which the COVID-19 crisis has impacted psychological well-being and work-related disability among frontline workers in the homeless sector. A second aim is to document rates of disability (stress) leave for staff through Workers' Compensation Board claims to further asses the extent of this impact. Finally, we will extend the study to four other Canadian cities. Together this data will present important information on staff stress, the impact of the COVID-19 virus, resultant disabilities, and possible mitigating factors resulting from organizational changes. Thus, this study would provide understanding of the pandemic's impact on this vital workforce and illuminate any organizational actions that informed mitigating strategies for staff well-being. This is especially critical as health authorities predict a second and possible third wave of infections that would seriously deplete an already highly stressed group of essential workers.",,-99,University of Calgary,144613.88,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P26782,429741,Pandemic Planning for Primary Care: Lessons from Four Provinces,"Family physicians (FP) play an important role in pandemic response and recovery. However, existing pandemic plans do not adequately incorporate FP. What are the roles of FP during a pandemic? What facilitates and hinders FP from fulfilling these roles? The goal of the project is to inform the development of pandemic plans for FP by examining experiences in four regions in Canada: Newfoundland and Labrador, Nova Scotia, Ontario, and British Columbia. The project is a multiple case study of regions in four provinces. Each case consists of a two-part mixed-methods design consisting of: 1) chronology of FP roles in the COVID19 pandemic response and 2) qualitative interviews with FP. In each province, we will create the chronology through a document review (supplemented, as needed, by key informant interviews) to describe key milestones in COVID19 pandemic and FP roles and responsibilities at each stage of the pandemic. Using the chronology as common frame of reference, we will conduct semi-structured qualitative interviews with FP who work in each region. In the interview, for each pandemic stage, we will ask FP to describe the facilitators and barriers to performing the proposed, actual and potential roles FP, and the influence of their gender on roles, facilitators and barriers. Results will provide government ministries, public health units, other health organizations, and FP evidence and tools (such as checklists) with which to respond to a second COVID19 wave and plan for future pandemics.",,-99,University of Western Ontario,228607.64,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Health Systems Research | Policies for public health, disease control & community resilience",Health service delivery | Policy research and interventions,2020 +P26783,488104,Elucidating the molecular mechanism by which bat IRFs modulate antiviral responses,"Despite being one in every five mammalian species, bats are an under-studied species. Bats can host different viruses, many that can be transmitted to humans. SARS-CoV-2, the agent of the COVID-19 pandemic, is thought to have originated in bats. Bats are exceptional agents of zoonotic transmission - hosting many diverse viruses, having a remarkable capacity to shed virus, and being closely related to humans. Although bats carry many viruses, they rarely, if ever, show clinical signs of disease. This is likely because bats and viruses have co-evolved over thousands of years, leading to suitable adaptations in the bat immune system. Bats have the ability to produce protective anti-viral molecules called interferons (IFNs) and other conserved components of the innate immune system that form the first line of defense against pathogens. The main goal of our proposal is to characterize how IFN is made and how it functions in response to viral infection in bats. Our research will specifically study the role of three transcription factors (IRF3, IRF7 and IRF9) that are involved in the production and/or activity of IFN. Information from this proposal will be foundational for understanding the molecular mechanisms by which bats adapt to a multitude of viruses that can potentially cause future pandemics. Furthermore, understanding bat-virus co-evolution and the tricks bats use to protect themselves from viral infection will provide a research framework for understanding human-virus co-evolution, with the long-term goal of prevention, control, and possible eradication of emerging viruses.",,-99,McMaster University,689338.26,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Animal source and routes of transmission",2023 +P26784,448940,Wastewater-Based Epidemiology of SARS-CoV-2 in Tertiary Care Hospitals: Advancing Wastewater Science and Providing an Early-Warning System for Hospital Transmission and Outbreaks,"Wastewater (WW)-based epidemiology (WBE) is an emerging science that seeks to understand the health of a population through sewage analysis. Early in the course of the pandemic, several groups demonstrated that monitoring for SARS-CoV-2 RNA in the community could predict future COVID-19 cases, hospitalizations and deaths. Our group proposes to focus this technology on hospitals in order to both refine WBE infectious disease science and to develop an ""early-warning"" system for future outbreaks. Hospitals hold great promise to advance WBE science by precisely identifying and tracking SARS-CoV-2; 1. Hospital WW from both in-building and municipal access points can be assessed minutes after release from patients/staff dramatically reducing the potential for signal degradation. 2. Near- precise accounting for all cases (regardless of symptoms) is possible in hospitals including the ability to relate individual patient-level data to symptom onset and potential exposure timing. 3. Hospital populations are well defined with respect to the daily number of patients (with relevant co-morbidities) and staff ensuring accurate denominators for bench marking. Accordingly, hospital-sewer pipes contain invaluable information that can be used to hone WW-science. Early data from our group demonstrates that WW-SARS-CoV-2 RNA from hospitals correlates with total active COVID-19 hospitalized cases - and yet is still able to identify changes associated with new hospital-associated infections and unit specific outbreaks. With this proposal we seek funding to study hospital-based WW monitoring across three tertiary care facilities (>2100 beds) enabling; 1. Validating WW SARS-CoV-2-RNA tracking as a model for passive infection monitoring in hospitals, 2. Developing and implementing real-time testing and reporting measures to enable outbreak avoidance, and, 3. Developing expertise in multi-level facility monitoring to identify, contain and mitigate SARS-CoV-2 spread.",,-99,University of Calgary,242264.36,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease surveillance & mapping,2021 +P26794,443065,COVID-19 Variant Network - Towards a comprehensive understanding of adaptive immunity to SARS-CoV-2,"The vast majority of people who get COVID19 fully recover from infection. This means that their immune system has successfully eliminated the virus. After we recover from a virus infection, the immune system leaves behind white blood cells, called memory cells, that can remember the previous infection and prevent that infection from recurring upon re-exposure. This is the basis of how vaccines work. After we recover from infection, two kinds of white blood cells persist, T cells and B cells. T cells and B cells have molecules on their surface that allow them to recognize the specific virus they were first exposed to. B cells give rise to antibody producing cells, while T cells can eliminate infected cells. Some antibodies can bind the virus in such a way that they fully block the virus from entering the cell. These are called neutralizing antibodies and these are ideal to fully protect us from being infected again. However, in some infections, weak antibodies, instead of neutralizing the virus, can actually make things worse by promoting uptake of the virus into cells or by overstimulating certain cells of the immune system. Therefore, there is a pressing need to understand the details of the immune response in COVID19 patients. We need to understand what parts of the virus are recognized when we have an immune response associated with a good outcome and what if any aspects of T and B cell responses are associated with a bad outcome. By studying the immune response in asymptomatic, mild and severe cases in depth, we hope to determine the correlates of a good immune response and use this information to design vaccines and to monitor people for the correct immune responses. For some infections T cell and B cell responses last a lifetime, whereas for other infections they do not last as long. Our study will develop the tools we need to follow how long the immune response to COVID19 infection lasts and to help with evaluating the level of protection in the population.",,-99,University of Toronto,78392.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P26795,443461,Characterizing signal 4 for CD8 T cell accumulation and memory formation during respiratory influenza virus infection,"Every year a few thousand Canadians die of influenza virus (flu) infection. Occasionally, we have pandemics of influenza virus, which can cause much more loss of life, such as occurred in 1918 when a new strain of influenza infected 1/3 of the world and killed more than 50 million people. Although we now have vaccines to prevent influenza infection, the virus is constantly changing, and vaccines must be reformulated annually. The current vaccines are based on generating antibodies to prevent infection. However, if a virus bypasses those antibody defenses and gets into your cells, then those cells become factories to make more virus. To eliminate the infected cells an immune cell called a CD8 T cell is required. These so-called ""Killer T cells"" are important in eliminating the infected cells to clear the infection. After you recover from infection, some of the T cells remain in place to prevent reinfection, referred to as memory T cells. One useful feature of T cells is that they tend to recognize more conserved regions of the flu virus, compared to antibodies, which recognize parts of the virus that can rapidly change to escape the antibodies. If we induce a really strong T cell response to influenza in our vaccines, this could add a level of protection against multiple influenza strains, especially when combined in a vaccine that induces neutralizing antibodies to influenza virus. Using a mouse model of influenza virus infection, our proposal is aimed at understanding the key components of the immune response to influenza virus that result in strong T cell memory against influenza virus. This could lead to new strategies for designing vaccines to influenza virus. Our results will provide insights into what we need to measure to see that we have the correct immune response after vaccination. The information we gain from this study could also help us learn how best to vaccinate against other respiratory viruses, such as SARS-CoV-2 the virus that causes COVID19.",,-99,University of Toronto,990632.97,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2021 +P26796,477316,"Identifying pathways for the emergence of mental health functioning in young adults from prenatal adversity, genetic susceptibility, the early environment, and intervening life stress - Leveraging hypotheses generated from an international birth cohort consortium to test specific mechanisms about anxiety, depression, and wellbeing.","Research indicates that adult mental health (illness and wellbeing) has its roots in early life. Being exposed to an adverse environment during pregnancy and early childhood, experiencing major life stressors during childhood and adolescence have been linked to mental illness in late adolescence and early adulthood. However, not all exposed children develop mental illness in adulthood. Our goal is to model the developmental pathways between exposure to adversity in pregnancy and childhood and adult mental health functioning by examining individual genetic risk and emotional and cognitive functioning during infancy, childhood, and adolescence. Using the Mental health in Adulthood: VAriability in Neurodevelopment and Resilience (MAVAN-R) cohort and the Development Research in Environmental Adversity, Mental health, BIological susceptibility and Gender (DREAM BIG) developmental consortium, we will ask the following questions: 1) Do early adverse environments and child genes predict emerging psychopathology/positive wellbeing? 2) Do major life events experienced by children/adolescents influence these relationships? And 3) Does emotional and cognitive functioning during childhood and adolescence interact with major life events to influence the above associations? This study is ideally situated to answer these questions by i) engaging community members; ii) using an established genetically informed database of fine grained assessments of mothers and children from pregnancy to six years of age, with follow-up assessments at age 13 years and during the COVID pandemic; iii) having an established international consortium (DREAM BIG) of 6 similar studies; iv) having an established Knowledge Users committee; and v) using advanced statistical analyses.",,-99,Lady Davis Institute for Medical Research (Mtl),73103.45,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26797,448878,Pulmonary vascular disease in patients with Long COVID,"Our goal is to determine the role of pulmonary vascular disease as a cause for persistent breathlessness (dyspnea) in patients with ""Long COVID"". Pulmonary Vascular Involvement in COVID-19 Inflammation, clotting (thrombosis), and damage to the pulmonary blood vessels has been demonstrated in patients acutely ill with COVID-19. Many patients who have ""recovered"" from COVID-19 continue to experience symptoms. Over half of patients report persistent dyspnea or fatigue at two months after hospital discharge, which has been characterized as ""Long-COVID"". Long-COVID patients often have normal breathing tests and most have normal chest x-ray findings. Pulmonary vascular disease is a possible cause of dyspnea in patients with normal pulmonary function, which is often difficult to detect. Exercise Hemodynamics Can Detect Pulmonary Vascular Disease Since the blood vessels in the lungs can be damaged during acute COVID-19 infection, we need to test ways to detect long-term pulmonary vascular disease. Pulmonary vascular disease often goes undetected with measures of resting lung and heart function. However, pulmonary vascular disease can be detected with exercise testing during right heart catheterization. Research Aims In Aim 1 we will the feasibility of a testing strategy for pulmonary vascular disease in patients with Long Covid across 3 Canadian centres. We will determine if it's possible to use a battery of tests including exercise right heart catheterization, imaging, and blood tests that can possibly detect early disease. In Aim 2 we will test whether patients with Long COVID have features of pulmonary vascular disease based on their exercise testing, imaging and blood tests. This study may establish whether some patients with Long COVID have pulmonary vascular disease. This project is necessary to inform future research so that we can better understand how common this condition is and whether it can be treated with drugs that are already available.",,-99,University of Calgary,232050.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P26799,449239,"Development of a deep learning framework to predict suicidal behavior, repeat hospitalization, and emergency department visits in mental health patients","The Canadian Institute for Health Information (CIHI) is a not-for-profit organization that provides data standards and collection, analytical reports, and analytical tools to the Canadian health sector. CIHI has a five to ten year mandate to prioritize analytics for vulnerable populations, including individuals suffering from mental illness. Advances in deep learning and the availability of large health datasets, broadly and in some cases exclusively available to CIHI, has paved the way for new approaches to health-related predictive analytics. As part of a postdoctoral fellowship at CIHI we propose to develop a deep learning-based framework that provides likelihood predictions for three future events in individuals with mental illness: 1) Probability of re-hospitalization, 2) Probability of emergency department visit, and 3) Probability of suicidal behavior. These predictions can help identify at-risk populations in order to adjust health services, reduce exposure to modifiable risk factors, evaluate suitability for patient discharge, provide early intervention, inform policy, and provide guidance for funding decisions based on predicted demands on mental health services. In addition to my work at CIHI, I will be part of the Ottawa Hospital Research Institute (OHRI) and the Department of Medicine at the University of Ottawa under the supervision of Dr. Peter Tanuseputro. The OHRI is the research branch of the Ottawa Hospital, which is one of the largest learning and research hospitals in Canada. With Dr. Tanuseputro I will be using health data to study the effects of physician mental health on patient outcome, with a focus on machine learning. This is a first-of-its-kind opportunity where patient health data can be linked to the treating physician and the physician's mental health. This project will help identify areas requiring attention in the well-being of physicians, and translates well to workplace mental health in general and during times such as COVID-19.",,-99,Canadian Institute for Health Information/CIHI (Ottawa),85055.91,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,Health Systems Research,Health workforce,2021 +P26800,442582,Active Surveillance for Safety and Effectiveness of Health Products for COVID-19,"Active surveillance is an approach to collect safety and, less commonly, effectiveness information from individuals who take prescribed or over-the-counter medications or other health products. Knowledge users have expressed a need to better understand the methodologies and tools used in active surveillance, the quality and trustworthiness of the data generated from these approaches and the optimal context for active surveillance once products are approved and available on the market. The COVID-19 pandemic has created a novel 'testing' ground for active surveillance approaches in health product effectiveness and safety. The urgency of the pandemic has also resulted in a number of patient treatment strategies that were implemented rapidly, and that may have been followed using active surveillance methods, or resulted in the development or adaptation of tools for collection of safety and effectiveness data. In this scoping review, we propose to review and clarify the state of knowledge for active surveillance approaches, tools and methods for evaluation of the benefits and harms of health products (drugs, biologics, health products) used for COVID-19. We will collect and synthesize research from the international community about: 1) the tools and methods used or proposed for active surveillance of the safety and effectiveness of health products used to treat COVID-19; 2) the capabilities and characteristics of these approaches; and 3) the quality and trustworthiness of the data collected. In addition, we will explore how approaches may have changed over the course of the pandemic, and/or with evolution of the understanding of COVID-19 disease and treatment options. This review will provide valuable information as to how various active surveillance methods and tools can be optimized for use in post-market drug safety and effectiveness contexts, and inform potential use of relevant approaches in Canada.",,-99,Ottawa Heart Institute Research Corporation (Ontario),96048.22,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Adverse events associated with therapeutic administration,2020 +P26807,494289,Creating a toolkit for trustworthy guideline development and implementation,"Health guidelines and recommendations are developed to provide advice to healthcare providers, program managers, policy makers and the public to make optimal healthcare decisions. Various Canadian and international organizations constantly seek to apply the latest and best practices in their guideline production. Resources such as the GIN-McMaster Guideline Development Checklist, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Approach Handbook, and many others are highly cited and frequently used by guideline developers to produce rigorous and trustworthy guidelines. However, the COVID-19 pandemic has taught us that guideline developers do not use the existing tools in optimal ways, in part because they are not easily accessible and sometimes outdated. The objectives of this project are to update the GIN-McMaster Guideline Development Checklist and develop an extension for guidelines developed in a pandemic, update the GRADE Handbook, and identify and catalogue available tools and resources for guideline development in a new interactive, web-based Guideline Development Toolkit. We plan to conduct systematic reviews and involve experts in consensus exercises and authoring of the updated Checklist and Handbook. We will develop and maintain a self-serve web portal for guideline developers to access latest methodology, tools, and resources. Use of the Guideline Development Toolkit will serve to ensure rigour in guideline development and, consequently, trust in guidelines by healthcare professionals and the public.",,-99,McMaster University,73558.84,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Unspecified,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2023 +P26811,498303,Trends and predictors of frequent and nonurgent use of emergency departments in Canada's paediatric population,"Emergency departments are an important part of healthcare systems as they help patients with urgent medical needs. The use of emergency departments in Canada by children has been increasing over time. This increase has a negative effect on how emergency departments work and leads to overcrowding. Right now, there is limited Canadian research about the how big this problem is in each community across Canada. We also do not know which groups of children use emergency departments the most, or which children go to emergency departments for nonurgent problems that could have been prevented or treated elsewhere. It would be very useful to know how individual characteristics such as a child's sex, age, family income, and the neighbourhoods they live in make some children more likely to use emergency departments, as well as how all of these patterns changed around the COVID-19 pandemic. The objective of this project is to produce up-to-date information on how many children in each community are frequent emergency department users and how many use emergency departments for nonurgent problems. We also aim to look at which groups of children use emergency departments, to see if there are common characteristics that could predict other children's outcomes. Together with our team of 25 researchers and clinicians, and national healthcare organizations for physicians and hospitals we hope to get this information into the hands of the decisionmakers who can find solutions to overcrowding at emergency departments.",,-99,University of Western Ontario,73558.84,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26812,450604,Accelerating stepped-care mental health with and for at-risk neurodiverse children and families using co-design,"The COVID-19 pandemic defied all estimates in length and mental health impact. Children with pre-existing mental health issues have been particularly affected. I-InTERACT-North is a virtual positive parenting support program designed for neurodiverse children (i.e., Brain Injury, Attention Deficit Hyperactivity Disorder, Autism). It helps improve family relationships, child behaviour and parent stress. Our team rapidly integrated a COVID-specific research element to our existing program and adapted to a stepped-care approach to enhance feasibility and better meet families' needs during the pandemic. Stepped-care offers effective treatment tailored in intensity and level of therapist involvement to family needs. The proposed study is a vital expansion of COVID-19 research already underway and ongoing given the protracted course of the global pandemic. It leverages an existing multi-phase project assessing the impact of I-InTERACT-North and informs next steps in larger-scale implementation. In the proposed study, we will extend and expand the existing COVID-19 response project in 3 ways; 1) continue to offer intervention to families already engaged as well as new prospective families given ongoing COVID-19 impact, 2) evaluate how program knowledge helped families in the context of the pandemic, and 3) partner with parent and community stakeholders to co-design future studies and scale wider I-InTERACT-North access, essential to extend and improve family mental health support. Our study is partnered with the Province of Ontario Neurodevelopmental Disorders (POND) Network, a large cohort of neurodiverse children. We will recruit parents of children ages 3-9 years across 4 major centers: Holland Bloorview, SickKids, University of Western Ontario, Queen's University. The purpose of the entire project is to evaluate stepped-care intervention for neurodiverse children and their families to mitigate mental health risk and family dysfunction and inform program scalability.",,-99,Hospital for Sick Children (Toronto),121492.22,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26813,468020,Stepped-Care Online Parent Training following Congenital Heart Disease: A Randomized Control Trial,"Babies born with serious medical conditions experience physical, learning, emotional, and behavioural challenges across their development. Despite the established importance of families in improving these outcomes, studies evaluating how mental health programs can improve parenting and child behaviour following serious congenital medical conditions remain lacking. We engaged parent partners to better understand mental health care needs in this population. We learned of the tremendous lack of programs helping parents address these challenges. Parents voiced strong interest in learning parenting skills to promote their child's behavioural and emotional development. An essential lesson learned during COVID-19 was that families need support options that are flexible and provided in steps that are matched to their needs (stepped-care). The current study will evaluate a virtual mental health parenting stepped-care intervention (I-InTERACT-North), a SickKids clinical research program with an emerging record of success prior to and during COVID-19. The fundamental goal of the current proposal is to determine if the I-InTERACT-North program works to improve positive parenting skills and child behaviour among families with children born with Congenital Heart Disease (CHD). We will also evaluate the acceptability and feasibility of the program among children and families to inform future delivery and multi-site trials. Currently, there is no evidence-based family treatment for children with early serious medical conditions, such as CHD and parents are eager for ways to enhance their child's well-being. Results will evaluate whether I-InTERACT-North can improve parenting and child behaviour in these families and inform future best clinical practices for this population.",,-99,Hospital for Sick Children (Toronto),580600.12,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26815,494298,Unraveling the Evolution of COVID-19: The Impact of Variant Mutations and ORF8 on Virus Replication and Pathogenesis to Enhance Pandemic Preparedness,"The response to the COVID-19 pandemic stands as a testament to scientific achievement. In less than a year, society transitioned from vulnerability to the SARS-CoV-2 virus to vaccine-driven protection. Coupled with mass immunization initiatives, these vaccines allowed the world to tentatively reopen. Yet, the pandemic is not over and continued waves of SARS-CoV-2 infections through world human population could pressure the emergence of new and potentially dangerous viruses. Global surveillance systems proficiently identify viruses with genetic changes, but the key challenge is distinguishing important genome alterations from benign ones. While informative methods can predict potentially important mutations based on sequence data only, linkage with empirical data are required to confirm and improve predictions. While there is some empirical data regarding how specific spike mutations affect infections the contributions of mutations in outside of spike, in other structural genes, within the non-structural genes, and accessory genes remain poorly characterized. To bridge this knowledge gap, this proposal embarks on a comprehensive exploration focusing on the Delta and Omicron variants and some of their non-spike mutations. By using reverse genetics and recombinant SARS-CoV-2 viruses this study will scrutinize the impacts of specific mutations, mutant genes, and accessory genes on virus growth, immune evasion, and disease progression. By unravelling the intricacies at play, this project aims to identify pivotal mutations. Such insights hold profound implications, guiding dangerous variant predictions, public health strategies, vaccine design, and treatment approaches. The pursuit of understanding within this initiative is not only a means to navigate the present pandemic but also creates the foundation for future pandemic preparedness.",,-99,University of Saskatchewan,73558.84,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P26816,484207,Reverse genetic analysis of mechanisms underlying convergent evolution of SARS-CoV-2 variants of concern and accessory protein functions,"The response to COVID-19 pandemic has been a triumph of science. At the beginning of the pandemic humans had no defense against SARS-CoV-2 and within a year effective vaccines and mass vaccination efforts have allowed society to reopen. However, the pandemic continues unabated despite the introduction of modified vaccines and regular vaccine boosting due to the emergence of new variants and continued evolution of the virus. The emergence of more viral variants is inevitable and continued waves of SARS-CoV-2 infections through world human population could pressure the emergence of new and potentially dangerous viruses. Worldwide surveillance identifies viruses having genome sequence changes, but which sequence changes lead to a dangerous virus and which are benign remain unknown. In addition, several sequence changes appear to have evolve many times independently. This process is called convergent evolution and is thought to be a product of positive selection where advantageous mutations accumulate and become prevalent. This proposal aims to identify mechanisms underlying convergent evolution of mutations in SARS-CoV-2 variants of concern by studying how individual or groups of mutations affect the replication, spread, and pathogenesis of SARS-CoV-2. Our goal is to identify mutations that signify a potentially dangerous variants to inform public health, vaccine and treatment decisions, and global efforts prevent the spread of disease.",,-99,University of Saskatchewan,73535.55,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P26817,468868,Technological Implications of Vaccine Certificates and their Public Health Impact,"During the COVID-19 pandemic, vaccine certificates were used worldwide to gate access to social events (i.e. restaurants, movie theatres, gyms, etc.), participate in recreational activities, and cross border travel. Vaccine certificates were criticized over concerns about data privacy, their ethical use, accessibility, and legal issues. Provincial and territorial approaches to vaccine certificates varied across Canada. This study will examine the impact and implications of vaccine certificates in Canada and the Organization for Economic Co-operation and Development (OECD) countries from a technological, equity/ethics/legal and public health perspective. We will use the United Kingdom Royal Society framework for vaccine certificates which holistically captures the implications of these certificates in twelve points. This project will identify the best practices for vaccine certificates and we will create recommendations for Canadian public health leaders for best practices, gaps in information, and ways forward.",,-99,Ottawa Hospital Research Institute,78410.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Approaches to public health interventions,2022 +P26818,475104,A policy analysis of strategies to develop a pan-Canadian immunization data repository,"The roll out of COVID-19 vaccines in Canada was the largest mass health intervention in the country's history. The roll-out also demonstrated the need for improved health data and information systems which are critical for the success of the immunization programs. Immunization registries are a key mechanism for collecting relevant immunization data. Developing a pan-Canadian immunization information system has faced challenges over the decades with data collection, information sharing agreements, and data standardizations. With the emergence of COVID-19, Canada has an urgent need for improved immunization information systems. This need will only grow with the emergence of new vaccines for all age groups. This project will help Canada fill this urgent need by first describing and analyzing the current immunization registry landscape. Based on this analysis, and the engagement of various stakeholders, we will draft a report proposing various policy options, with their advantages and disadvantages, to provide advice on how to fill the current gaps in pan-Canadian immunization data collection.",,-99,Ottawa Hospital Research Institute,102276.84,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience | Health Systems Research","Vaccine logistics and supply chains and distribution strategies | Policy research and interventions | Medicines, vaccines & other technologies",2022 +P26819,451181,Can Immunization Passports Improve Willingness to Vaccinate?,"To date, 60% of Canadians are fully vaccinated against COVID-19. Due to emerging, highly contagious COVID-19 variants, the number of Canadians needed to be vaccinated in order to achieve ""herd immunity"" may be close to 90%. Vaccine hesitancy can impact COVID-19 vaccination rates and the ability to fully re-open society. It is critical that as many Canadians that can get vaccinated, do. Vaccine passports provide proof of vaccination and could be used for international and domestic travel, in certain workplaces such as schools or hospitals or for large gatherings such as sporting events. It is possible that the use of vaccine passports could impact an individual's willingness to get vaccinated. In this study we will examine the impact of vaccine passports on willingness to vaccinate. First, we will conduct a literature review to evaluate research on the impact of COVID-19 vaccine passports on willingness to vaccinate. Second, we will conduct a national survey to find out Canadian's attitudes and beliefs surrounding the use of vaccine passports and how this might impact willingness to vaccinate. Third, we will review the online opinions made by individuals on new media comment sections. Finally, we will provide recommendations on whether and how vaccine passports should be implemented to increase vaccine uptake among Canadians. This research will inform the best practices for using vaccine passports among Canadians.",,-99,Bruyère Research Institute,119385.34,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P26820,452043,Building a coordinated evidence-support system in Canada to inform policymaking about health and social systems,"COVID-19 has created a once-in-a-generation focus on evidence across levels of decision-makers. Their decisions have profoundly shaped the pandemic response and will shape responses to future societal challenges. With the value of evidence having been broadly recognized by many system leaders, the pandemic has fast-tracked collaboration among decision-makers and researchers. However, drawing from a range of types of evidence to inform the full spectrum of decision-making is not yet routine. Now is the time to systematize the aspects of using evidence that have gone well and address the many shortfalls. This challenge has been taken up by the Global Commission on Evidence to Address Societal Challenges, which will generate recommendations and pathways to influence to strengthen evidence-support systems. This grant will harness insights from the Commission to determine applicability to Canada for building a more coordinated evidence-support system. We propose to: 1) develop and maintain a living and searchable Canadian evidence ecosystem map of all the nodes of evidence support that are specifically designed to respond to pressing policy needs; 2) evaluate COVID-19 advisory structures and processes at the federal, provincial and territorial level to identify key features and activities of the pandemic evidence response; 3) identify insights from those involved in decision-making about key COVID-19 policy responses about whether and how different forms of evidence support were prioritized and used by decision-makers during the pandemic, lessons learned about what's needed to support evidence-informed policy responses; and 4) convene a stakeholder dialogue to spark action for piloting and scaling up efforts to build a coordinated evidence ecosystem in Canada. Our findings will be essential to 'make the case' for why governments and other funders should invest in a more coordinated evidence ecosystem in Canada to inform policymaking about health and social systems.",,-99,McMaster University,177965.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P26821,460479,Prize - 202109PJT - Building a coordinated evidence-support system in Canada to inform policymaking about health and social systems,"COVID-19 has created a once-in-a-generation focus on evidence across levels of decision-makers. Their decisions have profoundly shaped the pandemic response and will shape responses to future societal challenges. With the value of evidence having been broadly recognized by many system leaders, the pandemic has fast-tracked collaboration among decision-makers and researchers. However, drawing from a range of types of evidence to inform the full spectrum of decision-making is not yet routine. Now is the time to systematize the aspects of using evidence that have gone well and address the many shortfalls. This challenge has been taken up by the Global Commission on Evidence to Address Societal Challenges, which will generate recommendations and pathways to influence to strengthen evidence-support systems. This grant will harness insights from the Commission to determine applicability to Canada for building a more coordinated evidence-support system. We propose to: 1) develop and maintain a living and searchable Canadian evidence ecosystem map of all the nodes of evidence support that are specifically designed to respond to pressing policy needs; 2) evaluate COVID-19 advisory structures and processes at the federal, provincial and territorial level to identify key features and activities of the pandemic evidence response; 3) identify insights from those involved in decision-making about key COVID-19 policy responses about whether and how different forms of evidence support were prioritized and used by decision-makers during the pandemic, lessons learned about what's needed to support evidence-informed policy responses; and 4) convene a stakeholder dialogue to spark action for piloting and scaling up efforts to build a coordinated evidence ecosystem in Canada. Our findings will be essential to 'make the case' for why governments and other funders should invest in a more coordinated evidence ecosystem in Canada to inform policymaking about health and social systems.",,-99,McMaster University,19714.7,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P26822,486062,Modelling the effect of public health interventions on COVID-19 case counts in a closed population through wastewater surveillance: implications in infectious disease outbreak response and epidemiology,"Wastewater surveillance is a rapidly advancing infectious disease management strategy that allows public health organizations to monitor community spread of a disease. Consistent wastewater monitoring can allow for early outbreak detection and inform rapid public health interventions accordingly. Although implementation of wastewater surveillance for SARS-CoV-2 has begun, several challenges remain regarding how to optimally use wastewater data to model community disease dynamics. There is a need to develop frameworks that more accurately translate information on viral wastewater concentration and community infection levels into measurable public health outcomes. This project aims to establish a framework that links wastewater surveillance data to community spread of SARS-CoV-2, and to integrate this data into mathematical models that account for public health responses. We hypothesize that SARS-CoV-2 concentrations in wastewater will be a highly accurate indicator of the effective reproduction number of the virus within the population of interest and that wastewater data will be highly sensitive to the implementation of public health measures in the community. The proposed model will provide insights on expected outbreak size and duration, while also allowing for an exploration of the impact that public health measures had on controlling outbreaks. This model framework will serve as an adaptable solution that can be applied to other pathogens in the future and will ultimately inform other public health response plans. This research fills a critical gap in using novel surveillance technologies to inform public health strategy and will serve as a valuable resource for preventing and controlling communicable disease in the future.",,-99,University of Toronto,13021.09,Environment | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2022 +P26828,481139,"Modelling, predicting and risk assessment of mpox (monkeypox) and other (re)emerging zoonotic threats to inform decision-making and public health actions: mathematical, geospatial and machine learning approaches","We will design and analyze epidemiological and geospatial models including artificial intelligence-based and mathematical models to study the epidemiology, transmission dynamics, and immunology and intervention strategies of mpox, and other zoonotic threats. These models will be used to generate valuable insights; predict the effectiveness of control strategies; identify modifiable risk factors which could be targeted for intervention, as well as other possible intervention strategies and inform public health decision-making; analyze public health interventions and risk management strategies; investigate the effectiveness of public health interventions, and thus provide rapid evidence to inform decision-making in Canada and/or globally. We will use biobehavioral data from PubMed data, and the recent survey by CDC/ECDC on the MSM community and modelling to study the different aspects and forecast the control interventions, risk factors; impact of mpox virus on sexually transmitted and blood-borne infections (STBBIs) by considering and examining Sex-and Gender-Based Analysis Plus (SGBA+). The host immune response to mpox plays an essential role in disease pathogenesis and clinical manifestations, even though it is little understood. Thus, our models will also provide insight into the factors that shape the virus' within-host dynamics in the presence of infection-induced and vaccination-induced immunity. We plan to use risk-map assessment and geospatial analysis to identify hotspots for (re)emergence of zoonotic threats that will be used by countries' decision-makers and health units in pandemic surveillance and response to improve preparedness. This will explore the complete scope of potential health and other impacts of proposed public health interventions, and capture the broad range of risks and benefits tied to different mpox and other zoonotic threats prevention and control strategies in Canada and/or globally.",,-99,"York University (Toronto, Ontario)",360190.62,Other,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes | Transmission dynamics including risk & determinants of acquisition | Ongoing assessment & evaluation of surveillance,Canada,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P26829,491669,Positive Epidemiology - Pre and Peri-Pandemic Psychological Resilience in Older Veterans in the Canadian Longitudinal Study on Aging,"How and why do some older adults adapt and thrive better than others in the face of challenges? Do prior life experiences, such as having served in the military, play a role in the development of resiliency at older ages? These are questions we will explore in this research project. Several U.S. studies have highlighted the resilience of Veterans, but we have not found any comparable studies in Canada. Resilience is often characterized by personal growth following stressful experience(s) and the development of coping skills (e.g., mental, emotional, and behavioural flexibility) in the face of adversity. Sometimes referred to as post-traumatic growth, this resiliency has been suggested to occur in Veterans following trauma and/or military-related experiences (in some cases, decades after military service). It is well accepted that the impacts of the COVID-19 pandemic have disproportionately affected different population groups (e.g., older adults). Research on Veterans specifically suggests features of both resilience and vulnerability in response to the pandemic. Prior military trauma may translate to difficulty coping with the pandemic (e.g., due to increased social isolation), but may also reveal the resiliency of older Veterans during challenging times. In the Canadian Longitudinal Study on Aging (CLSA), more than 4,000 participants self-identified as Veterans. Using data from the CLSA collected over time, we will examine psychological resilience in older Veterans in Canada for the first time, how resilience manifests over time, and how it relates to pandemic experiences and health states.",,-99,Research Institute of the McGill University Health Centre,51847.33,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P26839,451465,Mobilizing Communities: Enhancing partnerships between schools and youth hubs for mental health and well-being,"The growing mental health (MH) crisis has only worsened since COVID and the fall-out from this is expected to be felt for years to come resulting in a sustained negative impact on MH. Despite this, MH supports and services are significantly lacking; timely access to care is ladened with barriers to services especially for young people, including those from Black, Indigenous and People of Colour (BIPOC) communities who have faced deepened inequities as a result of the pandemic. Hence, we need earlier innovative approaches to MH service delivery, before young people reach the crisis point. Mobilization between schools and community MH (i.e., youth hubs) supports has an important role in a stepped care approach and is vital to improving timely access to care, to reducing inequities and to improving overall MH of young people. The goal of this youth-centered study is to implement and evaluate a community-based MH program using an evidence-based effective stepped approach for young people that involves mobilizing partnerships between schools and youth hubs. This study involves the partnership with a well-established Manitoba (MB) youth hub (NorWest) and an urban school division (Seven Oaks School Division - SOSD). Youth attending SOSD highschools and key stakeholders (e.g., teachers, clinicians, counsellors) will be invited to take part in the study. Multiple data collection methods (e.g., individual and focus group interviews, arts-based methods) will be used, guided by principles of equity, collaboration and partnership. Short-term, this study will yield information on whether the community-based MH program shows promise as an acceptable, appropriate and effective program in promoting MH and well-being for young people. Long-term, the findings will inform the next steps in the research program including adapting and implementing the community-based MH program with additional school-youth hub partnerships across MB and could be applied to youth hubs across Canada.",,-99,University of Manitoba,431338.66,Human Populations,Unspecified,Adolescent (13 years to 17 years),Urban Population/Setting,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26840,451091,Advancing Patient-Centered Care in Young People Living with Chronic Pain,"Chronic pain is a common, serious and poorly understood problem among young people. Moreover, living with chronic pain is so much more than the pain itself. A wide range of domains may be affected by chronic pain including sense of self, relationships, physical functioning and sleep, mood, mental health, school and work. COVID-19 has further exacerbated the challenges experienced by young people with chronic pain (YCP). While living with chronic pain can have a tremendous toll on a young person, YCP voice that their experience is not understood. If we hope to improve care for YCP that is patient-centered, it is essential we engage YCP in research. The aim of this patient-oriented national study is to advance patient-centered care for YCP with an emphasis on YCP delineating their experiences, needs, priorities for care and preferred outcome. YCP will also co-design arts-based knowledge translation (KT) products to advance key stakeholders' (e.g., parents, YCP, health and social service providers) understanding of the experiences of YCP. YCP across Canada will take part in individual interview and arts-based methods. Integrating creative arts-based methods with qualitative approaches will afford the opportunity and space for YCP to articulate their multifaceted nature of their experiences. Key stakeholders from across Canada will be engaged in a series of focus groups to garner their recommendations on the use of arts-based KT products to advance patient-centered care for YCP. Adopting a patient-oriented approach that includes YCP as co-researchers and arts-based approaches is innovative and a necessary first study for this research program. Short-term, advanced understanding of the experiences of YCP including their needs, priorities for care and preferred outcomes will emerge. Long-term, the next steps in the research program includes developing as well as scaling-up and testing supports and services for YCP that are grounded in the experiences of YCP.",,-99,University of Manitoba,473565.96,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26841,468307,Understanding the Impacts of COVID-19 on the Mental Health and Well-being of Canadian Youth Coming of Age in COVID Times,"The COVID-19 pandemic, an 'unprecedented historical event,' has affected the daily lives of all peoples. In particular, youth across the globe have been and continue to be impacted in substantial ways, which includes a growing mental health (MH) and well-being crisis in youth. The short- and long-term consequences of the pandemic on the MH and well-being of this generation are only just beginning to be determined. Warranted is an ongoing examination of the impacts and lived experiences of COVID-19 on the MH and well-being of youth coming of age in COVID-times, considering the pandemic and the fall-out from it are expected to affect youth for years to come. The goal of this youth-centered, mixed-methods study is to understand, from a life course perspective, the impacts of COVID-19 on the MH and well-being of Manitoba (MB) youth coming of age, to provide recommendations to improve services and supports for this population and to inform preparedness for future health crises and pandemics. Individual and population data will be collected from youth residing in MB. Multiple data collection methods (e.g., interviews, arts-based methods, and population level administrative data) will be used, guided by principles of equity, collaboration and partnership. This first-of-its-kind project will generate important ongoing and longitudinal evidence on the impacts and lived experiences of COVID-19 on the MH and well-being of youth coming of age to inform evidence-based practices and policies. Recommendations and solutions to ameliorate the impacts of COVID-19 on the MH and well-being of youth in MB will emerge. Long-term, feedback from this study will be used to inform the next steps in the research program, including developing new services, programs and interventions that will ultimately contribute to the MH and well-being of youth in MB and across Canada, as well as shape future responses to new health care crises and pandemics.",,-99,University of Manitoba,595261.73,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26842,460244,Addressing the indirect and wider health impacts of COVID-19 on families of children living with disabilities,"Children with disabilities are one of the most marginalized and vulnerable groups of people. Families of children with disabilities encounter many challenges and inequities, such as economic and social disparities, poorer health and social exclusion. COVID-19 has further exacerbated the inequities experienced by these families who have faced disproportionately greater challenges throughout COVID-19. Moreover, the pandemic has impacted how children with disabilities receive care including a greater emphasis on the provision of virtual care. Families of children with disabilities have experienced delays in their ability to access both healthcare and social care including rehabilitation. This lack of access to care is even more pronounced for Black, Indigenous and People of Colour families and those who are lower income. Even with improvements in the pandemic, it is unlikely that care will return to its pre-pandemic normal. To better address the indirect and wider health impacts of COVID-19 on families of children with disabilities, needed is research that will result in an equitable and targeted model of care for these families. This study aims to develop a model of care using an equity lens that ameliorates the indirect and wider health impacts of COVID-19 on families of children living with disabilities. Families from Manitoba (MB) will participate in family interviews. Focus groups combined with arts-based methods will take place involving service providers and families of children with disabilities in MB and across Canada. Recommendations for an equitable model of care that ameliorates the indirect and wider health impacts of COVID-19 for families of children with disabilities in MB will emerge. Long-term, the work will be used to inform patient-oriented service delivery and outcomes nationwide for this currently underserved and vulnerable population which is vital for future health emergencies and pandemics.",,-99,University of Manitoba,343298.71,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +P26843,473348,Connections Matter: Fostering social connectedness in youth to optimize mental health and well-being,"Social connectedness, which refers to a sense of belonging to an individual or group, is a central human need. It is a known protective factor for mental health (MH) and well-being, and against at-risk health behaviours for youth, which has lasting effects into adulthood. The COVID-19 pandemic has had detrimental effects on youth's social connectedness. The fall-out from this is expected to be felt for years to come, resulting in a sustained negative impact on the MH and well-being of youth. This study will address this gap and is in line with priorities identified by 'Inspiring Healthy Futures Vision for Canadian children, youth and families': the need to foster social connectedness, mobilize community action and partnerships including schools to support our youth, and engage with youth to create solutions. The aim of this multi-methods, youth-centered, arts-based longitudinal study is to gather evidence that will result in the creation of a toolkit that can be used by schools to foster social connectedness in youth to optimize their MH and well-being. Youth attending Grade 6 in the Seven Oaks School Division (SOSD) in Manitoba (MB) and key stakeholders (e.g., families, peers, teachers, counsellors) will be recruited. The youth will be followed as they transition from grade 6 to grades 7 and 8. Youth and stakeholders will take part in a variety of data collection methods including individual and focus group interviews and arts-based methods. A toolkit co-designed by youth will be implemented and evaluated over the course of the study. Short-term, a toolkit will emerge that can be used by schools in the SOSD to help foster social connectedness in youth, with the ultimate aim of advancing their MH and well-being. Long-term, this study will be used to inform the next steps in the research program, including adapting, implementing and evaluating the toolkit in other schools in MB with potential for future scale-up and testing across Canada.",,-99,University of Manitoba,76662.06,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26844,475319,Partnering for Youth Mental Health and Well-Being: Co-Designing Policy Recommendations and Research Priorities for Manitoba Youth Hubs,"The mental health (MH) crisis facing Canadian youth is a public health concern with MH challenges becoming more severe and affecting more youth Also concerning is the emerging evidence of the negative impact of the COVID-19 pandemic on youth MH, which is expected to be felt for years to come. In efforts to identify solutions to the MH crisis and in line with the United Nations Convention on the Rights of the Child, which highlights the rights of youth to express their views and participate in matters affecting them, engaging youth in the development of MH policy and research priorities is needed. Youth hubs are the ideal venue to engage youth in these ways as they aim to advance youth MH. The purpose of this youth-centered study is to gather evidence that will inform MH and well-being policies and research priorities at youth hubs in Manitoba (MB). Central to this study is engaging youth in the co-design of policy recommendations and research priorities by providing them with a leadership role in this process. Youth attending MB youth hubs and key stakeholders will be invited to take part in the study. Youth will participate in focus groups and a survey. Youth co-researchers will engage key stakeholders in a series of meetings to move the youth co-designed MH and well-being policy recommendations and research priorities into action. Arts-based methods will be used throughout the course of the study. Short-term, this study will provide important evidence to inform policies and research priorities specific to advancing MH and well-being for youth attending youth hubs in MB. Youth co-researchers will build capacity specific to policy and research development. Future work involves using the findings to advance next steps including undertaking identified policy recommendations and research priorities for MB youth hubs. Long-term, the findings may be used to inform best practices on how to engage youth in policy and research across integrated youth services in Canada.",,-99,University of Manitoba,73412.81,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2022 +P26845,484159,Understanding Manitoba Childrearing Families' Decisions to Vaccinate Against COVID-19 and Influenza,"Vaccinations are effective at protecting people from serious illness, hospitalization, and death, and they are recognized as the safest and most valuable public health measure against infectious disease. Despite recent warnings from public health officials regarding potential harmful impacts due to the convergence of COVID-19 and seasonal influenza, along with respiratory syncytial virus (RSV), particularly for the very young, parents' support for vaccinating their children varies. Influenza vaccination coverage for Canadian children and adults remains low, and while over 80% of children aged 12-17 years and adults have been vaccinated with at least one dose of a COVID-19 vaccine, it is of concern that parents' and youth's willingness to get vaccinated is not universal, given the ongoing outbreaks of COVID-19 variants. Considering parental perceptions of vaccines directly influences the vaccination status of their child(ren), we need to approach the study of COVID-19 and influenza vaccination rates and decisions within the context of the family unit. The goal of this 5-year mixed-methods study is to determine family unit vaccination rates, and to understand the perspectives and experiences of Manitoba (MB) childrearing families' decisions to vaccinate their family members against COVID-19 and influenza, with the intent to provide recommendations for public health. Individual data (e.g., family and focus group interviews, arts-based methods) and population data will be collected from MB childrearing families. This is a first-of-its-kind project focusing on vaccine uptake using family unit vaccination rates, experiences and perspectives, which will help inform childrearing families' decisions to vaccinate against COVID-19 and influenza. Recommendations and solutions to inform family decisions (adults, children, family unit), reduce vaccine hesitancy and healthcare service use, and promote vaccine uptake will emerge.",,-99,University of Manitoba,73535.55,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2023 +P26847,462068,Probing the role of mechanical rigidity in viral xrRNAs as the key to preventing their degradation by host RNases,"RNase enzymes are part of the cellular defenses against viral infection, digesting RNA from invading viruses. Some viruses evade RNases by partially blocking digestion so that the RNases produce viral RNA fragments, called xrRNAs, that interfere with cellular processes to enhance infectivity. We recently showed that a Zika virus xrRNA acts as a mechanical roadblock preventing RNases from digesting the viral RNA because of its rigidity. It is unclear if the same is true for other xrRNAs, and it remains to be determined what mechanical and/or structural features of xrRNAs are required in general to produce RNase resistance. We will answer these questions by surveying xrRNAs from viruses like dengue, Zika, West Nile, and yellow fever. We will use laser tweezers to measure the mechanical rigidity and probe how it relates to RNase resistance. We will test if rigidity is sufficient to explain RNase resistance in each case and determine the features required for this resistance, by knocking out specific interactions in the xrRNA with mutations or binding short oligomers to specific parts of the xrRNA to prevent them from folding. Next, we will study the interactions between xrRNAs and RNases by using lasers tweezers to watch single enzyme molecules as they digest RNA messages containing xrRNAs, verifying directly that xrRNAs block RNase motion and observing how RNases respond when they encounter xrRNAs. Finally, by mapping xrRNA folding pathways using these measurements, we will identify key intermediates in which xrRNAs can be 'trapped' to prevent resistance and test if using oligomers to do so is effective at reducing virus pathogenicity in cultured cells. This work will clarify how resistant structures form in xrRNAs, how they interact with RNases, and what are the critical components that could be targeted as a potential therapeutic strategy, and it will provide proof-of-principle that targeting xrRNA mechanical resistance may be effective as an antiviral treatment.",,-99,University of Alberta,733712.27,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P26849,456332,AAV-vectored immunoprophylaxis for the prevention and treatment of infectious diseases,"Adeno-associated virus (AAV)-mediated expression of pathogen specific, broadly protective monoclonal antibodies (mAb) has been demonstrated to provide protection against a variety of infectious diseases in a range of animal models and is now being tested in two human clinical trials for human immunodeficiency virus (HIV) (NCT03374202 and NCT01937455). Our patented (U.S. patent US 10,806,802) AAV-mAb expression platform utilizes a novel, rationally engineered AAV6 mutant capsid, termed AAV6.2FF, which has been shown to be highly efficacious as a prophylactic against Ebola virus and C. Difficile toxin challenge, among other infectious diseases. In this proposal we aim to optimize and expand our vectored immunoprophylaxis (VIP) platform to aid in the clinical translation of this promising alternative vaccine and therapeutic strategy. Specifically, we will investigate AAV-vectored mAb expression kinetics, anti-drug antibody development, effect of pre-existing immunity, and ways to modulate gene expression and in a range of larger animal models including guinea pigs, ferrets, sheep, and non-human primates. Finally, we will implement novel vector design improvements and explore new applications for AAV-vectored mAb expression.",,-99,"Avamab Pharma Inc. (Calgary, Alberta)",78858.79,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +P26850,478670,AAV-vectored immunoprophylaxis for the prevention and treatment of infectious diseases,"Adeno-associated virus (AAV)-mediated expression of pathogen specific, broadly protective monoclonal antibodies (mAb) has been demonstrated to provide protection against a variety of infectious diseases in a range of animal models and is now being tested in two human clinical trials for HIV. Our patented AAV-mAb expression platform utilizes a novel, rationally engineered AAV6 mutant capsid, termed AAV6.2FF, which has been shown to be highly efficacious as a prophylactic against Ebola virus, Marburg virus, respiratory syncytial virus, and C. Difficile toxin challenge, among other infectious diseases. Here we aim to optimize and expand our vectored immunoprophylaxis (VIP) platform to aid in the clinical translation of this promising alternative vaccine and therapeutic strategy. We hypothesize that AAV-mAb expression can prevent clinical illness caused by viral infectious diseases in NHP animal models and strategies can be employed to evade pre-existing immunity, mitigate immune-mediated clearance of vector transduced cells, and lower vector doses resulting in long-term mAb expression. To address this hypothesis, we will execute the following aims: (1) Evaluate innovative strategies to enhance AAV-mAb expression in the presence of pre-existing immunity, and/or to facilitate repeat administration in rodents, (2) Analyze the efficacy of a pan-filovirus AAV VIP platform expressing a bispecific mAb in rodents, (3) Investigate mechanisms of ADA responses to AAV-mAb expression in a large animal sheep model and (4) Based on the optimization steps in Aims 1-3, characterize the AAV VIP platform, including evaluation of ADA response, in a MARV NHP challenge model Expertise: Dr. Wootton is expert in the field of AAV biology and vector design. Dr. Banadyga is an expert in high consequence pathogen animal model and CL4 containment challenge studies. Dr. Susta is an expert in animal models of infectious disease and anatomic pathology.",,-99,"Avamab Pharma Inc. (Calgary, Alberta)",559734.96,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease | Marburg virus disease,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2023 +P26856,485594,3-years into the COVID-19 Pandemic; How Can Health Behaviours Continue to Protect Your Mental and Physical Health?,"The COVID-19 pandemic has drastically altered the way people live, work, and interact with others. Having to constantly adapt to an evolving situation, can lead to feelings of uncertainty, anxiety, and stress. Navigating the new normal has become a challenge for many people, but there are strategies that can help individuals cope and maintain their physical and mental health. The pandemic has also created significant challenges for public health, with people's behaviours playing a crucial role in the spread of the disease. Behavioural medicine is a field that aims to understand how behaviour influences health and wellness, and it has become increasingly relevant during the pandemic. The Café Scientifique will encourage public discussions about the role of health behaviours around COVID-19 given the current state of the pandemic. By implementing this Café, we hope to improve public awareness and understanding of the role of behavioural medicine in reducing the impact of COVID-19. By helping individuals feel more empowered and in control during these still uncertain times, we believe that this will encourage individuals to make informed decisions and ultimately improve the public's physical and mental health.",,-99,"Concordia University (Montreal, Quebec)",4412.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts,2023 +P26857,475185,A survey of Canadian critical care staffing to inform current policy and future need,"Intensive care units (ICUs) are where the sickest patients in the hospital receive their care. The physical beds and equipment are important to allow for safe care. However, having the right staff (e.g. doctors and nurses, pharmacists, physical therapists) is just as important to ensure patients do well in the ICU. We know that having doctors and nurses specifically trained in critical care is best, but we know very little beyond that. Right now we don't know how many doctors, nurses, and other members of the care team are routinely taking care of patients in ICUs, or how that might have changed from before COVID-19. We don't know how many patients each doctor or nurse is usually caring for during the day, and how many other team members, such as physical therapists and pharmacists are employed in each ICU. The goal of this grant is to identify exactly what is known already, and then to survey each ICU across Canada to understand the current staffing of their ICUs. This basic information is essential to then create a document that can provide guidance to all the hospitals and ICUs across the country regarding staffing for ICUs.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",109655.17,Human Populations,Unspecified,Unspecified,Unspecified,Other,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Health Systems Research,Health leadership and governance | Health workforce,2022 +P26859,495568,"al-time epidemiological intelligence to inform control of SARS-CoV-2: improving the precision, validity, and granularity of estimates of the effective reproduction number in Canada",N/A,,-99,Université de Bordeaux I (France),4414.31,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Europe,Unspecified,,,,,,Epidemiological studies,Disease transmission dynamics,2023 +P26866,448814,"An exploration of the drivers of COVID-19 vaccine hesitancy to identify and develop community-informed approaches to improving understanding and trust in public health measures among Indigenous peoples in remote and rural communities in Ontario, Canada.",Indigenous Peoples and communities have been adversely affected by the COVID-19 pandemic in Canada. A better understanding of the drivers of vaccine hesitancy and approaches to improve vaccine confidence as well as determining strategies that can be used to improve uptake of vaccination and public health measures to prevent COVID-19 infection and illness are essential to keep individuals and communities safe. We will utilize community-based research approaches to better understand Indigenous perspectives regarding COVID-19 public health infection prevention measures including COVID-19 vaccination. We will also utilize these research approaches to better understand how Indigenous Peoples perceive and incorporate public health recommendations to remain healthy. We will also explore barriers and enablers to accessing health care or other essential health-related services within and outside of their community during the COVID-19 pandemic so that barriers to staying healthy during the COVID-19 pandemic can be addressed.,,-99,"Queen's University (Kingston, Ontario)",221859.04,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P26867,473493,Comparative dynamics of SARS-CoV-2 and enterovirus/rhinovirus outbreaks.,"The public health measures implemented during the pandemic have dramatically changed the epidemiology of respiratory tract infections (RTI). While the number of infections caused by many common RTI such as influenza, have been dramatically reduced, some RTI, such as rhino- and enteroviral infections continued to co-circulate with SARS-CoV-2, often exceeding the burden of COVID-19. The factors responsible for transmission of some but not other respiratory pathogens are poorly understood but likely depend on both the pathogen's capacity for rapid dissemination and the host's ability to mount effective immune responses. A better understanding of these factors could help guide future guidelines for RTI prevention. Therefore, here I propose to characterize in detail the patterns of RTI pathogen transmission, and to study immune responses associated with the different RTI transmission patterns during the pandemic. These studies will be done in the communities of Canadian Hutterites, who live communally in relative isolation from urban centres, thus presenting a unique model to study the dynamics of natural infection spread and disease prevention. I am hopeful that this research will shed light on the dynamics of common RTI dissemination to facilitate a better understanding of disease spread within human populations.",,-99,McMaster University,98689.66,Human Populations,Other,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics",2022 +P26868,454967,"The BEACONS Platform - Comprehensive biomarker analysis for prediction of clinical course and management in acute coagulopathy in sepsis, trauma, cardiac arrest, and COVID-19","Canadians who suffer from severe traumatic injuries are dying from bleeding and clotting defects because critical illness disrupts the body's natural clotting system. This process, called coagulopathy, is common and poorly understood, and is also a common cause of death and disability in Canadians who arrive to the emergency room with cardiac arrest, severe infections, and with COVID-19. Because we cannot predict whether patients will end up with predominantly bleeding defects or clotting defects, it is difficult to decide whom to treat with drugs that either prevent bleeding, or blood thinners to prevent clotting. We believe that that the body's response to injury and infection causes measurable molecules of inflammation and heightened blood clotting. Our approach aims to find these molecules to be used to identify patients that will require specific targeted treatment before they suffer from coagulopathy. To achieve this, we have assembled a collaborative effort between the largest intensive care hospital networks in Canada with the Thrombosis and Atherosclerosis Research Institute (TaARI), the largest and most comprehensive Canadian facility dedicated to the study of inflammation and blood clotting diseases. Our extensive infrastructure allows us prospectively collect blood samples from patients suffering from trauma, sepsis, cardiac arrest, and COVID-19. Using state-of-the-art methods developed by our group, we will measure biomarkers from the pathways that control inflammation, blood vessel integrity, clot formation, and clot breakdown. Using a machine learning algorithm recently published by our group, we plan to identify and compare which markers can predict coagulopathy in these diseases. By understanding how coagulopathy develops in the early stages of critical illnesses that commonly affect Canadians, we may be able to identify those patients requiring aggressive therapy earlier in the course of the disease.",,-99,McMaster University,130311.23,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2021 +P26869,486077,Characterizing changes in youth cannabis use after the pandemic: A longitudinal cohort study,"Over the past two years of the COVID-19 pandemic youth cannabis use has increased. In the 2020 Canadian Cannabis Survey (CCS), 31% of those aged 16-24 reported increasing their use due to the pandemic while in 2021 this proportion rose to 43% [1,2]. Considering the significant impact that the pandemic has had, youth have been using cannabis to deal with boredom, stress, anxiety, loneliness and depression (1,2,3,4,5). However, it is still not known how youth cannabis use changes over time after the pandemic. This question is important to address given the harm that frequent cannabis use can have on youths' developing brain and mental wellbeing [8]. This study will follow young Ontarian cannabis users ages 16-30 over a year to examine their cannabis use. The objectives are twofold, first to describe how cannabis use has changed, and second to characterize types of changes in relation to youth's experiences and mental health. Youth will be asked questions about their cannabis use, mental health, impact of the pandemic on cannabis use, belief/perceptions about cannabis, influence of cannabis marketing, and health education. The recent reports of greater cannabis use among youth presents a health challenge. This proposed research attempts to address this problem by contributing to Canada's understanding of how and why young people change their cannabis use.",,-99,McGill University,13021.09,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P26871,460231,"Endometriosis and chronic pelvic pain: impact of the COVID-19 pandemic on virtual, surgical, and multidisciplinary care","Endometriosis affects ~10% of the population and is a common cause of chronic pelvic pain. It is defined as tissue resembling cells in the uterus (womb), being present outside of the uterus. In this proposal, we will examine the impact of the COVID-19 pandemic on endometriosis and chronic pelvic pain. At our centre during the pandemic, there was incorporation of virtual care, conversion of a multidisciplinary pain program to virtual, and delays in surgical treatment of endometriosis. Our first aim is to the examine how the pandemic and these practice changes impacted patients with endometriosis/chronic pelvic pain, such as pain levels, mental health, quality-of-life, and disease severity. Our second aim is to assess how diagnosis and management of endometriosis/chronic pelvic pain changed with virtual care only, compared to an in-person assessment with physical examination and point-of-care ultrasound, with particular focus on impact on surgical treatment. The third aim is to specifically examine the experiences of patients with endometriosis of East and South-East Asian descent, given the geopolitics of the pandemic and anti-Asian discrimination. We will conduct both quantitative (statistical) analyses and an arts-based study using Photovoice to capture the experiences of these individuals. This research will provide a comprehensive picture of the impact of the COVID-19 pandemic and will have direct implications for quality improvement of the care provided for endometriosis and chronic pelvic pain.",,-99,University of British Columbia,402976.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26874,457360,Virtual Innovation for Stroke Investigation and Treatment (VISIT),"Every 9 minutes, someone in Canada experiences a stroke. Stroke is the third most common cause of death among Canadians. Risk factors for stroke include high blood pressure (hypertension), sugar (diabetes), cholesterol (hyperlipidemia), and an irregular heart rhythm (atrial fibrillation). Regular visits to the doctor's office are important for diagnosing these stroke risk factors early and starting treatments to reduce the risk of stroke. The COVID19 pandemic has dramatically changed these visits from in-person to phone or video encounters. Despite the new and widespread use of telemedicine, it is not clear if all regular stroke or vascular health care can be maintained. We will study stroke care and outcomes in residents of Ontario, Canada. Compared to before the pandemic, we will evaluate whether doctor visits, screening for vascular risk factors, and unplanned medication interruptions have been negatively impacted during the pandemic, despite the availability of telemedicine. We will study people without stroke and those who had a hospitalization for stroke. We suspect that care after a hospitalization can be maintained with telemedicine because these patients are well connected with the health system. However, in Ontarians who have chronic vascular conditions without any hospitalization, we suspect doctor visits and regular care may be reduced or delayed. We will identify patient groups who may be particularly vulnerable to difficulties with telemedicine, including those who are older, women, those who experience socioeconomic deprivation, or who live in rural regions. Our research team will be working closely with policymakers and stroke organizations in Ontario and nationally. This study will help us understand if telemedicine is a good tool to enable regular health care to continue when in-person care is not possible, and it will inform policies to better support individuals who have difficulty accessing telemedicine.",,-99,"Sunnybrook Research Institute (Toronto, Ontario)",78976.51,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Women | Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Digital Health,,,Canada,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26883,450646,Collective Action for COVID-19 Recovery: Co-designing physical activity interventions with adolescents and caregivers in Peel Region,"Peel region has been a hotspot during the COVID-19 pandemic, resulting in strict lockdowns for long periods of time. In response to the devastating impacts of the pandemic on families, 26 community organizations came together, as the Peel Family Support Network (PFSN), to provide collective resources and support. Our research team is currently leading a community needs assessment alongside the PFSN to understand the nature and impacts of COVID-19 restrictions on children, youth, and families in Peel and to identify resources and services required to support and sustain health and well-being during pandemic recovery. Based on responses from over 1,860 caregivers and youth, engaging in physical activity has been identified as a priority area for adolescents (aged 12-18) and caregivers of adolescents. To meet the needs of Peel's diverse communities, this project engages a Community Advisory Board of adolescents, caregivers, service providers, and researchers to guide all project activities. Photo-based methods, a community prioritization activity, and a ""hackathon-style"" event, will be used to explore the physical activity experiences of adolescents and their caregivers throughout the pandemic and co-create physical activity interventions to move knowledge to action to promote and sustain physical activity during pandemic recovery. As many communities lack adequate resources for physical activity, COVID-19 recovery presents an opportunity for collective innovation, where adolescents and caregivers can co-create meaningful and accessible physical activity interventions with service providers. By conducting this work in partnership with the PFSN and community members, we expect these physical activity interventions can be adapted for use with other age groups, will be relevant to diverse communities across different geographical settings, and can be tested and evaluated in other regions of Ontario and Canada.",,-99,"Trillium Health Partners (Mississauga, ON)",120992.69,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P26884,460339,A collaborative response to addressing family violence with racialized and diverse communities during pandemic recovery in Peel region,"The COVID-19 pandemic has greatly impacted the health and well-being of individuals, families, and communities around the world. Public health interventions such as social distancing and ""lock-downs"" have led to indirect and wider health consequences such as family violence. Improving access to survivor-centred services and community resources can help improve outcomes for people experiencing family violence, yet many survivors and their families face barriers to accessing holistic and culturally appropriate services. Previous research with racialized and diverse communities shows the need for multilevel approaches that consider individual, family, community, and systemic factors. The Peel region, Ontario, in which our project is based, has seen some of the highest rates of COVID-19 infections in Canada and is an ideal setting for understanding how racialized and diverse communities have experienced family violence throughout the pandemic. Building from the region's Community Safety and Well-being plan, we will engage a diverse group of community members who have experienced family violence, service providers, and researchers to guide all project activities. Through photo-narrative methods, a community prioritization activity, and a hackathon-style event, we will explore experiences of family violence and co-create preventative interventions during pandemic recovery that are evidence-informed and culturally sensitive to help racialized and diverse families at-risk of experiencing family violence in Peel. This project presents an opportunity for collective innovation to develop meaningful and accessible interventions that could prevent family violence during future health emergencies and pandemics. By centering community voices, we expect these family violence preventative interventions will be relevant to diverse communities across geographical settings and can be tested and evaluated in other regions of Ontario and Canada.",,-99,"Trillium Health Partners (Mississauga, ON)",277134.84,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts,2021 +P26885,443128,COVID-19 Variant Supplement - Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),"An epidemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly in China and 27 other countries. As of 15 February 2020, over 69,000 cases of COVID-19 have been reported, with 1,666 deaths. The enormous health, economic and social impact clearly make it paramount to better understand the pathogenesis of COVID-19, as no specific drugs are available to combat COVID-19. To address this issue we have put together a world-class international research team of basic scientists and clinicians who have a track record of working together and have access to resources [SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",,-99,"Keenan Research Centre (Toronto, ON)",39196.27,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2021 +P26886,422719,Molecular and cellular therapies against COVID-19 using angiotensin-converting enzyme 2 (ACE2),"An epidemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly in China and 27 other countries. As of 15 February 2020, over 69,000 cases of COVID-19 have been reported, with 1,666 deaths. The enormous health, economic and social impact clearly make it paramount to better understand the pathogenesis of COVID-19, as no specific drugs are available to combat COVID-19. To address this issue we have put together a world-class international research team of basic scientists and clinicians who have a track record of working together and have access to resources [SARS-CoV-2, cell and animal models, a candidate drug, biotech company, and patients (in China)]. This research proposal focuses on the role of angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor to enter human body. We propose to do basic studies to examine the specific mechanisms involved, as well as to perform a clinical trial in COVID-19 patients in China using recombinant human ACE2 (rhACE2).",,-99,"Keenan Research Centre (Toronto, ON)",758305.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Therapeutics research, development and implementation",Pre-clinical studies | Clinical trial (unspecified trial phase),2020 +P26887,485890,Investigating the Immune Mechanisms Underlying the Development of Rheumatological Complications Post-COVID,"The coronavirus pandemic has severely affected global healthcare systems and changed life as we know it. It is now apparent that beyond the resolution of infection, a subset of COVID-19 patients who recover sustain a range of persistent symptoms ranging from chronic fatigue, shortness of breath and joint pain to cognitive impairments and cardiovascular complications. This constellation of symptoms is known together as post-acute COVID-19 sequelae (PACS) or long-COVID. Persistent autoantibodies post-COVID are well documented 3 months, 6 months, and 12 months following infection indicating that the inappropriate activation of the immune system and the development of autoimmune responses plays a role in continued symptomology post infection. Furthermore, these changes in the immune system may lead to the development of chronic and serious rheumatic diseases like lupus, rheumatoid arthritis, vasculitis, scleroderma, and others. My Master's thesis aims to understand the precise mechanisms of immune system impairment which initiates autoimmunity, describe the B-cell populations which may mediate auto-antibody formation, and describe how the post-COVID condition is influenced by aberrant neutrophil activation and coagulation dysfunction. A thorough understanding of these mechanisms will assist in identifying early biomarkers of disease and establish a path to possible treatment avenues and therapeutic interventions.",,-99,McMaster University,13021.09,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Clinical characterisation and management,Disease pathogenesis | Post acute and long term health consequences,2022 +P26889,499188,Trajectories of work productivity loss: Working from home and insights during COVID-19,"Many people living with chronic conditions can have their health well managed and treated. However, if a health condition progresses or worsens, people may attend at work but cannot perform at full capacity (i.e., presenteeism), take sick leaves, or have to reduce routine work hours or even completely stop working. When people are older, they are more likely to suffer from one or more health conditions. Thus, work productivity loss due to health problems may be more substantial among middle-aged or older adults. People with health problems may start with low presenteeism, gradually increase presenteeism and then stop working especially if they are not well supported by workplaces and governments. However, few studies have examined how work productivity loss is changing over time and how presenteeism leads to future unemployment or retirement especially among an aging population. Meanwhile, due to the COVID-19 pandemic and the transition to working from home (WFH), it is also important to consider the impact of COVID-19 and WFH on presenteeism. Based on the Canadian Longitudinal Study on Aging data, this study is to address the knowledge gaps and includes four specific objectives: 1) to examine how employment status changes over time among middle-aged or older workers and what factors are associated with the changes; 2) to measure how current presenteeism relates to employment status in the short-medium term within the context of COVID-19; 3) to measure how presenteeism changes over time among those who remain employed and examine the relationship between WFH during COVID-19 and this change; 4) to examine any sex and gender differences. The study will provide evidence to inform workplace and government supports to help maintain the work productivity of middle-aged or older workers and retain them in the workforce, and to inform whether WFH is an option for such a purpose.",,-99,"Centre for Health Evaluation & Outcome Sciences (Vancouver, BC)",51847.33,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Gender,,,Canada,,"Secondary impacts of disease, response & control measures",Economic impacts | Social impacts,2023 +P26892,473334,"Traditional, Complementary, and Integrative Medicine for patients with COVID-19: Living network meta-analysis and Rapid Recommendations","Patients and clinicians worldwide need trustworthy, rapidly updated guidelines to inform their treatment of patients with acute and Long COVID-19. Although 80% of Canadians report using at least one Traditional, Complementary, and Integrative medicine (TCIM) in their lifetime, the overwhelmed healthcare system has limited capacity, and no Canadian or globally trustworthy guidelines and evidence summaries exist on TCIM for COVID-19. Optimal evidence summaries need to be up to date and differentiate well-done studies producing valid results from poorly done studies that are likely to be misleading. Interpretation of the evidence requires considering all the relevant studies addressing each treatment. In addition, it is vital to revise evidence summaries frequently as new information is published. To create trustworthy evidence summaries, we will search many databases to detect all relevant COVID-19 trials, evaluate the design and conduct of the studies, and combine all studies addressing each relevant question producing a single analysis for each outcome that patients feel is important. The resultant review allows patients and clinicians to compare all treatment options against standard care and against one another. These optimal evidence summaries will inform trustworthy practice guidelines. We will create trustworthy guidelines by constituting a panel that includes experts in COVID-19, TCIM clinicians and researchers, experts in assessing evidence, front-line clinicians treating COVID-19, and patients who have lived experience of acute and Long COVID-19. Panel members will be free of conflict of interest. These recommendations will be produced quickly and constantly revised as researchers publish new data. Finally, we will work with the World Health Organization for the guideline and one of the most impactful medical journals, the British Medical Journal, to publish the results online(free access for all) and as WHO guidelines on their website.",,-99,McMaster University,76662.06,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P26893,485892,COVID-19 mortality among institutionalized individuals,"Individuals living in institutionalized environments are more susceptible to the spread of COVID-19, and often the poor living conditions may lead to worsening health outcomes. Therefore, we are interested in investigating whether institutionalized individuals have a higher COVID-19 mortality rate than those who are not institutionalized. This study will utilize the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN), which will include data on consenting patients arriving at the emergency department for COVID-19 treatment. We will match institutionalized patients with non-institutionalized patients and examine the mortality rates and any additional variables that modify the result.",,-99,University of British Columbia,13021.09,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,,,,Canada,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2022 +P26894,455131,High fidelity perfusable heart-on-a-chip for modeling viral induced myocarditis,"Patients with viral infections, especially COVID 19, frequently developed myocarditis, an inflammation of the myocardium that can result in severe morbidity and mortality. However, the underlying mechanisms are still a mystery. Heart-on-a-chip combined with stem cell technology presents a unique opportunity to tackle the issue, as human tissues can more precisely recapitulate human diseases. However, cardiac muscle contains extensive vascular networks and immune cells that are challenging to recreate in vitro. To overcome this obstacle, I propose to design a culture system with opposing hollow pillars, serving as tissue forming templates, vascular perfusion inlet/outlet and force sensors. Perfusable tissue will be created around the hollow pillars with sequential formation of the vascular layer, heart muscle tissues with resident macrophages and circulating immune cells. The tissues will be electrically conditioned to reach advanced maturation approaching adult-like phenotypes. The cardiac and vascular functional assessments will be benchmarked with healthy adult myocardium. All cells in the matured tissue will go through single-cell sequencing to compare with reported genetic profiles of cells in adult myocardium. Finally, patients with and without viral myocarditis will be added to induce myocarditis. The sars-Cov2 vascular infection will be an alternative approach. The cardiac and vascular injuries will be evaluated to identify the consistency with the clinical results of the donor patients. Moreover, EV, cytokines and antibodies will be compared between groups through RT-PCR, ELISA and mass spectrometry to identify the potential target responsible for myocarditis. The final candidates will be tested on the heart-on-a-chip to confirm the findings. The proposed tissue model will be the first to precisely recreate adult-like cardiac tissues and will be a valuable asset to investigate cardiovascular-related disease mechanisms and therapeutic interventions.",,-99,University Health Network (Toronto),71078.85,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Innovation,,,Canada,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Disease pathogenesis,2021 +P26897,485629,"Public Outreach to inform how Mobility Data is being used in Public Health: Past, Pandemic, and Future.","Smartphones have become an essential part of our daily lives, with 6.6 billion users globally at present and expected to rise to 7.5 billion by 2026. The location data from smartphones are collected in real-time by network providers to maintain connectivity. These data are compiled into large mobility datasets. Researchers worldwide have used these data sources in the last decade to detect patterns in the population that would help with infectious diseases such as Malaria, Cholera, Rubella, HIV (Human Immunodeficiency Virus) etc. The COVID-19 pandemic saw the use of these data sources by public health organizations across the globe, in the face of a virus that was spreading rapidly within the population. Use of this data has been linked to predict the virus' spread and the extent to which public health measures were followed by citizens. Public Health Agency of Canada recently admitted to using mobility data to track population movement during lockdown. While this is providing exciting new frontiers for future research projects using real-time big data sources, this has also brought up concerns for the ethical implications of using non-consensual data in research. Discussions regarding these concerns have been initiated between individuals in government and research communities. However, most of the general public are still unfamiliar with the existence and use of mobility data. As such, the purpose of this Café is to bring this conversation to the residents of Kingston, Ontario. This Café is an invitation and education session to inform the community on what ""mobility data"" means, and what the implications are for using such data for research, and for the community members to voice their perceptions and concerns with this data use.",,-99,"Queen's University (Kingston, Ontario)",4412.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Canadian Institutes of Health Research (CIHR),Canada,Americas,Americas,Unspecified,Data Management and Data Sharing,,,Canada,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2023 +P26901,XM-DAC-41302-IP20-NPL828,The government and social partners have promoted fundamental principles and rights at work to protect workers especially from unacceptable forms of work,The government and social partners have promoted fundamental principles and rights at work to protect workers especially from unacceptable forms of work,,2020,N/A,1656863.11,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P26937,GB-GOV-1-301168,"Hygiene, Handwashing & Behaviour Change Coalition for COVID 19 response programme","To develop an innovative partnership with Unilever to provide funding, for a 'ÄòHygiene, Handwashing & Behaviour Change'Äô Coalition for Covid19, matched with in-kind support and technical expertise by Unilever. Under Unilever leadership, the coalition will bring together academia (e.g. London School of Hygiene & Tropical Medicine), INGOs (e.g. Oxfam) and UN agencies, to deliver mass communications, hygiene products and digital behaviour change programmes on the importance of hand and environmental hygiene in low- and middle-income countries. This will build on recent investments Unilever has made in response to Covid19 and will allow scale up across multiple countries.",,2020,N/A,99831713.05,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Communication,2020 +P26938,GB-GOV-1-301293,UK Support to the Global Partnership for Education 2021-2026,"This programme will allow GPE to expand its programming for primary and secondary education, addressing the global learning crisis, including the setbacks posed by COVID-19, particularly to girls. The programme will help GPE deliver funding to transform education in countries that are home to 1.1 billion school-aged girls and boys. GPE estimates that its support, alongside other education spend, will help partner countries get 40 million more girls into school and support 17 million more girls to read in Lower Income Countries (LICs, 70%) and Lower Middle-Income Countries (LMICs, 30%) over its five-year strategic plan.",,2023,N/A,518675911.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2023 +P26940,GB-GOV-10-GAMRIF-WP6-GARDP-CORE,Global Antimicrobial Resistance Innovation Fund (GAMRIF) - GARDP Core Funding,"The Global Antibiotic Research & Development Partnership (GARDP) is a non-profit product development partnership. It is a research and development initiative addressing global public health needs by developing, delivering and assuring sustainable access of new or improved antibiotic treatments. UK Department of Health and Social Care (DHSC) funding through the Global AMR Innovation Fund (GAMRIF) will support GARDP'Äôs core activities. DHSC will provide unearmarked, core funding to GARDP to support the development and delivery of new treatments for drug-resistant infections that pose the greatest threat to health, with GARDP having a primary focus to enable distribution of treatments to people in low- and middle-income countries and with antimicrobial resistance (AMR) recognised by the UN General Assembly as critical to achieving the Sustainable Development Goals (SDGs).",,2020,N/A,107222697,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P26942,GB-GOV-1-400133,ASEAN-UK Supporting the Advancement of Girls'Äô Education (SAGE) Programme,"This programme will help to improve the learning outcomes, agency and freedoms of women and girls and other left-behind groups across the full range of countries in ASEAN, in line with the commitments to ASEAN as a Dialogue Partner. It will deploy technical advice to support regional partnerships and reform initiatives that can influence and multiply domestic and multilateral education finance. In Low- and Lower Middle-Income Countries, activity will focus on basic education. We will provide technical assistance, capacity building and evidence assessments to help ASEAN Member States (AMS) design and implement more cost-effective measures to address the foundational learning crisis, including post-COVID-19 recovery. It will also help to expand access to high quality digital skills, technical and vocational education with a focus on enabling marginalised adolescent girls ty digital skills, technical and vocational education with a focus on enabling marginalised adolescent girls.",,2024,N/A,30890107.2,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Unspecified,Unspecified,Women | Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2024 +P26975,GB-GOV-13-FUND--GCRF-MR_T029862_1,Developing effective rodent control strategies to reduce disease risk in ecologically and culturally diverse rural landscapes,"Diseases transmitted from rodents to humans are a serious threat to health, with the highest risk in low-income countries. The risk from rodent-borne infections (RBI) depends on the abundance of infected rodents, as well as how socio-cultural practices and beliefs influence human-rodent interactions. Many rodent species implicated in disease transmission are also pests that feed on crops and stored food, and consequently management to reduce rodent numbers could have a wide impact on health and well-being. However, controlling rodent populations effectively is challenging. Breeding and movement from adjacent populations may rapidly cancel out the impact of control. Innovative approaches that exploit ecological understanding of where and when rodents breed have been developed in the agricultural sector, primarily in Asia, with communities working together to target control and significantly reduce crop damage. However, such techniques are poorly developed in Africa, and their potential to reduce the risk from RBI is unknown. In some circumstances, changes to rodent movements following control could increase disease transmission and prevalence in rodent populations, potentially increasing risk to humans. Ultimately, this project aims to reduce the risk from RBI in Africa by increasing the knowledge and expertise needed to develop holistic rodent management applicable for local conditions and communities. Working with communities in Tanzania and Madagascar, in the first stage of the project we will address specific unanswered questions, whilst in the second phase we will develop and test rodent management strategies. Two questions we will address are: how do rodent movements change after localised control, and how does control influence the prevalence of RBI in rodent populations? To make sure our approach is widely relevant, we will work with rodent species and diseases that have large impacts and contrasting ecologies. We will focus on the multi-mammate mouse, a key pest species in Africa, and the black rat, a globally important invasive pest, and consider three RBI: plague, leptospirosis and rickettsioses, which differ in key aspects of their epidemiology. We will combine field studies with sophisticated computer models to explore how control in different locations and at different times of the year impacts on rodent movement, abundance and the prevalence of RBI. The results will provide important insights into how ecological and epidemiological factors influence the impact of different control strategies on RBI and rodent damage. We will also work with local communities using a range of approaches to address three further questions: how do communities perceive the health threat from rodents, how do communities currently interact with and manage rodents, and how feasible are different management strategies? As effective control strategies have to be accepted and sustainable for local communities, we need to understand local perceptions and practices. For example, high labour requirements during specific key periods in the agricultural cycle may mean that some rodent control strategies are not feasible. The insights from this research during the first phase of the project will be used to inform the development of community-led trials of rodent management strategies. The impact of these trials on rodent abundance and the prevalence of RBI will be monitored, and the results used to refine and test our computer models. We will use this comparative study to identify common features that determine the effectiveness or uptake of a strategy. To ensure our research informs policies, we will conduct workshops with service providers involved in agriculture, health and the environment. Across these sectors we will explore current attitudes, policies and communication practices, and provide training in adaptive management approaches. Our project will also build research capacity through collaboration and training.",,2021,N/A,2497929.16,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Vector biology | Vector control strategies | Impact/ effectiveness of control measures,2021 +P26976,GB-GOV-1-301566,United Kingdom (UK) Support to the Pandemic Fund,"The programme will provide early seed funding towards the Pandemic fund - a new Financial Intermediary Fund for pandemic prevention, preparedness and response hosted by the World Bank",,2023,N/A,29596177.27,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2023 +P26977,GB-GOV-13-FUND--GCRF-AH_V006517_1,Far apart but close at heart: How do arts organisations in Latin America support the mental health of young people online during a global pandemic?,"Project explores how arts organisations in Latin America are changing the delivery of activities to online platforms to support the mental health of young people in response to a global pandemic and impact of change on participants SDG 11,10,17 COVID-19",,2020,N/A,159310.39,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P26978,GB-GOV-13-FUND--GCRF-AH_V007025_1,Empowering Brazil's impoverished communities through critical decision-making. A communitarian communicative strategy,"Project assess how fake news undermines local pandemic mitigation efforts among vulnerable groups in metropolitan areas in Brazil, and how the spread of fake news among those groups undermine local pandemic mitigating efforts. SDG 10, 11, 4 COVID-19",,2020,N/A,161508.84,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Policy research and interventions,2020 +P26979,US-EIN-37-1552838-81,Eneza - Enabling children to continue learning during the COVID-19 pandemic,"Build awareness of its service in the country. The grant allowed Eneza to step up its marketing activity to inform potential new users about its EdTech solution. Increase server capacity in response to new demand, build a chatbot to address queries from users, and add examination content to the service.",,2020,N/A,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P26980,GB-GOV-1-301426,Safeguarding the rights of LGBT+ communities in the post-pandemic Commonwealth.,"To build on the Commonwealth Equality Network'Äôs (TCEN) track record of success supporting LGBT+ civil society organisations in Commonwealth countries. The project seeks to ensure that LGBT+ organisations continue to be supported to sustain and advance their work protecting and upholding the rights of LGBT+ people, and be better prepared to bring LGBT+ people'Äôs concerns to the attention of those in positions of power.",,2021,N/A,1250597.91,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Gender,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26981,GB-GOV-13-FUND--GCRF-AH_V006533_1,Repair and Repurposing for Pandemic Resilience in Low Income and Humanitarian Settings,"Project aims to ensure the continued provision and access to basic energy needs for refugees/displaced people in Burkina Faso and across Sub Saharan Africa by collecting data and repair and repurposing of humanitarian technology SDG 7,3 COVID-19",,2020,N/A,70025.83,Unspecified,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P26982,GB-COH-03580586-5000693254,Climate Finance Accelerator,"The Climate Finance Accelerator (CFA) is a four-year (2020-2024) technical assistance programme developed by the International Climate Finance (ICF) Team of the UK Government'Äôs Department for Business, Energy and Industrial Strategy (BEIS). The CFA is being delivered by an Alliance led by PricewaterhouseCoopers LLP (PwC UK) with support from Ricardo-AEA and a number of other organisations and independent subcontractors. Lack of funding and technical support, an unsupportive policy environment, and now the uncertainty caused by the COVID-19 pandemic, can present considerable obstacles in the climate finance supply chain for low-carbon projects in middle-income countries. The CFA aims to tackle those challenges by supporting countries to develop a sustainable pipeline of bankable, low-carbon projects in the context of the ever-growing need for sustainable recovery triggered by the pandemic.",,2020,N/A,11107048.43,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P26983,GB-CHC-228248-P000511,"Support to Rural Water Supply, Sanitation and Hygiene in Tanzania","This proposal seeks to bring Tanzania into a group of countries that ODI is working on regarding poverty monitoring, during financial year 2021-22, such that indepth qualitative research in a few sites more and less affected by Covid 19 can complement the available quantitative analysis on the consequences of the pandemic, especially for those at the bottom of the wellbeing distribution.",,2021,N/A,65712.67,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2021 +P26984,GB-GOV-1-301274,Democratic Republic of Congo Food Insecurity Crisis Reserve Project,"To mitigate the direct socio-economic and humanitarian impact of the Covid-19 pandemic through cash transfers to families in Kinshasa and food insecure populations in the Great Kasai provinces. Improving access to food and basic services, whilst reducing the loss of income amongst already food insecure people, while also support their efforts to become self-reliant and the early development of a Government shock -responsive social protection system.",,2020,N/A,5242675.51,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P26985,XM-DAC-47066-DP.2287,Strengthening Humanitarian Preparedness and Response (SHPR) Programme,"The overarching objective of this project is to ensure improved well-being, health and dietary diversity of the most vulnerable refugee and host community in Cox's Bazar, Bangladesh, as part of IOM's response to the COVID-19 pandemic. Planned activities complement IOM's exiting programs - livelihoods, water, sanitation and hygiene (WASH), health including mental health and psychosocial support (MHPSS), and site development. IOM will be the managing agency for this short-term consortium project.",,2021,N/A,1917902.39,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Indigenous People,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26986,XM-DAC-47066-IS.0048,"Engage, Connect, Empower","The project aims to increase community resilience and cohesion through youth participatory action to address the critical gap in public life participation of youth that compromises their cohesiveness and capacity to withstand future social, economic and environmental shocks and stressors in a country already severely impacted by a weak economy, lack of opportunities, scarcely efficient social services and precarious social safety-nets and high rates of out-migration, all further exacerbated by the consequences of the COVID-19 pandemic.",,2020,N/A,258770.01,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P26987,GB-GOV-1-301162,"UK contribution to the IMF Catastrophe, Containment and Relief Trust (CCRT) II","To support the IMF Catastrophe, Containment and Relief Trust (CCRT), which provides debt relief to low-income countries that are hit by catastrophic natural disasters or public health emergencies. This will help the poorest countries to manage the health impacts and economic disruption of the COVID19 global pandemic. The CCRT helps the poorest countries by covering the cost of their debt repayments owed to the IMF. This means that national budgets are freed up to spend on addressing natural disasters or health emergencies.",,2020,N/A,186175478.1,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Health Systems Research | Secondary impacts of disease, response & control measures",Health leadership and governance | Economic impacts,2020 +P26988,GB-GOV-1-400012,Contribution to the IMF's Resilience and Sustainability Trust,"This payment is a contribution of up to ¬£50mn to the reserve account of the International Monetary Fund's Resilience and Sustainability Trust (RST). The RST is a new lending facility to support low and middle-income countries foster resilience to macroeconomically-critical challenges including climate change, energy resilience, and pandemic preparedness, through long-term concessional lending. This ODA grant contribution will provide the reserves required to facilitate 1.8bn Special Drawing Rights (about ¬£2bn) of lending to the Loan Account of the RST.",,2023,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2023 +P26989,GB-GOV-13-FUND--Newton-ES_V013114_1,Adapting DIALOG+ and building capacity in schools to support mental wellbeing and resilience in post-conflict Colombia during the COVID-19 pandemic,Deliver signficant reseach funding for internationally competitative and innovative collaborative projects between researchers from Colombia and United Kingdom that will allow the pursuit of shared research interests.,,2021,N/A,264748.36,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P26990,GB-GOV-13-FUND--Newton-ES_V013157_1,The impact of the Covid-19 pandemic on the mental health of workers in health services: building resilience in post-conflict territories,"COVID-19 was declared a global pandemic by WHO on March 11. Even though Colombia declared a national emergency early in the pandemic (March 17) and has taken other mitigation measures, the infection has spread across the country. Colombia is the eleventh highest in the world in terms of the number of cases. One of the significant concerns during the pandemic is the high demand for health services that exceed the service capacities. For these demanding healthcare needs, COVID-19 pandemic can affect the physical and mental health of healthcare workers (HWs) (including clinical and non-clinical staff). During this pandemic, HWs are exposed to high levels of stress due to long working hours, changes in their functions, and fear of the disease. In addition, HWs can be exposed to the death of patients, hopelessness, and ethical dilemmas. These stressors can increase the risk of developing mental health problems. The most important reasons to study this problem in Colombia are the high risk of mental problems in HW, lack of resources in health services, and the history of violence due to the armed conflict which has meant that HWs were highly stressed even before the pandemic arrived. We therefore propose to: 1. To study the mental health of health workers in Colombia and some regions of the Development Programs with a Territorial Approach (PDET), and to assess how mental health problems vary according to the personal history of violence and resilience levels 2. To assess the association between stressors derived from the COVID-19 pandemic and mental health in the health workers in a first measurement, and at 3, 6 and 12 months of follow-up 3. To explore how a history of exposure to armed conflict modifies the effects of the stressors from the COVID-19 pandemic on mental health. 4. To design and evaluate the feasibility and satisfaction of an eHealth-based intervention to prevent symptoms of depression and anxiety, and increase resilience in health workers Methods: 1) Cross-sectional study of 3,000 health workers (clinical and non-clinical personnel including administrative personnel and support personnel) to estimate the prevalence and distribution of mental health stressors. Sampling will be convenient through health institutions, medical associations, hospitals and social networks. In the cross-sectional study, we will also include a specific sample of health workers from Florida, Pradera, Apartado and Turbo (n = 150) and will compare the proportions of mental health problems between the national level with the specific data of these regions (prioritized as post-conflict). 2) Cohort study: we will include healthcare workers (n=3,100) from the cities of Bogota, Medellin and Cali who will be followed up -3, -6, and -12 months after the first measurement. This information will be used to assess the medium-term impacts of the pandemic stressors on mental health as well as the protective and risk factor for mental health 3) Design and evaluation of an intervention based on eHealth that allows the detection and prevention of depression and anxiety and promotion of resilience in health workers. 4) component of social appropriation of knowledge that includes dissemination strategies of research results, eHealth intervention for prevention of mental health problems in health workers. In addition, we will design educational material in videos and infographics to promote the mental health of health workers, and conduct forums with the presentation of the results, as well as produce short reports for decision makers.",,2021,N/A,453555.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P26991,GB-GOV-1-300801,Evidence for Health - E4H,"This programme builds on earlier UK investments in Pakistan. It will strengthen the ability of Pakistan'Äôs health system to recover from COVID-19 pandemic as well as building resilience for future pandemics. It will strengthen evidence-based decision making in the health sector and support the implementation of Universal Health Coverage (UHC) and build climate resilient health systems including for vulnerable communities. It will focus technical assistance on the provincial governments of Punjab and Khyber Pakhtunkhwa (KP), with support for the Federal government as well support flood recovery.",,2022,N/A,47481629.22,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Health Systems Research,Health service delivery,2022 +P26992,GB-COH-1110949-415995,DFID Business Partnerships for the Global Goals,To provide match funding support to enable Multinational Companies to develop inclusive business models which will deliver benefits to poor people through their core business activities.,,2020,N/A,5225143.17,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P26994,GB-GOV-1-301528,PURCHASE (Priorities for Universal Health Coverage: Realising Cost-effective Health Services for Everyone),"Constrained fiscal space in many countries, exacerbated by the COVID-19 pandemic, is making it challenging to increase much needed domestic investment in health. Countries must therefore not only mobilise more domestic financing behind UHC but spend the money they have for health better. PURCHASE will fund: advocacy and engagement on the goal of UHC and strengthen regional leadership, technical capacity and partnerships for better decision-making in health across Africa to help governments prioritise this agenda and make better decisions, informed by robust evidence, on how to get more health for their money and accelerate progress towards the goal of universal health coverage. This will deliver benefits across populations, with an intention to see accelerated access for more vulnerable and marginalised groups to essential quality health services, without financial hardship.",,2024,N/A,5410528.1,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P26995,GB-GOV-13-GCRF-AH_C_UG-Cvd2019-A4WQ92W,Cultivating through Crises: Empowering African Small-Holders through Histories of Creative Emergency Response (CCEASH),"CCEASH aims to adopt a historiographical approach in order to demonstrate how smallholder farmers in Elgeyo-Marakwet County (EMC), Kenya, innovate and respond in times of crisis. The recent surge in desert locust swarms, allied to flooding and drought, across East Africa present an unprecedented urgent threat to local livelihoods, where failed harvests and crop destruction, coupled with pandemic-related collapse of global market chains, has raised concerns surrounding food shortages and impending economic collapse. In response to these crises, the Kenyan Ministry for Agriculture has called upon farmers and other stakeholders to rapidly intensify production (http://www.kilimo.go.ke/covid-19/). COVID-19",,2021,N/A,175017.48,Unspecified,Black,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P26997,US-EIN-37-1552838-98,"Safe Water Network - The Ghana government issued a directive to provide free water to domestic users at the start of the COVID-19 pandemic. This increased the strain on SWN'Äôs operations, as a result of greater demand.","Hire additional water station operators, while enabling the organisation to undertake additional maintenance activities to maintain rapid repair times and frequent water quality testing.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P26998,XM-DAC-301-2-109602-001,Learning and engagement within the Climate and Resilience Partnership,"This project supports the review of initiatives funded under the Climate and Resilience (CLARE) partnership that have the potential for scaling the uptake and impact of research on climate change adaptation and resilience. It also aims to inform the design of the next generation of climate change research programming. Spread over multiple months, it will provide a facilitated virtual learning process among a set of currently supported researchers to take stock of their progress and lessons learned to date, including the synthesis of results and avenues for future action. It will provide opportunities to collectively reflect on approaches, activities, and actions to scale and explore themes of interest, such as gender, social inclusion, and adaptation to programming during the COVID-19 pandemic. This exercise will also gather feedback on the future of the CLARE partnership and how to adjust current implementation. This project is part of the Climate and Resilience (CLARE) partnership, a joint initiative between IDRC and the UK'Äôs Foreign, Commonwealth and Development Office. CLARE aims to scale the uptake and impact of climate research and to support research that will accelerate adaptation and catalyze climate action in the Global South.",,2020,N/A,24873.72,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27000,GB-GOV-13-FUND--GCRF-MR_T029781_1,Building healthy communities in urban Brazilian slums,"Urbanisation provides one of today's major public health challenges. In low income cities, infectious diseases, linked to contaminated water and food and limited sanitation, exist alongside increased risks of air and water pollution. Social violence is often epidemic. The young are amongst the most vulnerable but also often those with least voice in decisions about their future. The city of Salvador, Brazil, where this project is based, exemplifies these problems. Financial constraints mean that there is an urgent need for sustainable, locally-developed interventions to improve multiple health outcomes in these settings, and in selecting interventions, we need a framework that targets the common drivers of poor health. Community-based mitigations must be based, also, on local knowledge of determinants of risk, and managed to ensure that they can be adapted to the local context. Here, therefore, we adopt an approach based on adaptive management, through which an initial, evidence-based management plan, developed through consensus between experts and local stakeholders, is repeatedly re-assessed and, if appropriate, modified (adapted) in the light of additional evidence, collected on an on-going basis. Our aim is to enhance wellbeing in communities in Salvador, and provide a blueprint for similar projects in urban slums worldwide. We will focus on the interacting effects of infectious diseases that represent three different transmission routes, and on interventions to mitigate their risk. 1) Leptospirosis and enteric (gut) infections, which are environmentally transmitted via rats, water and soil where sanitation is poor. 2) Zika, Dengue, and Chikungunya, caused by mosquito-borne pathogens whose risk is associated with mosquito infestation and reproduction. 3) Directly transmitted infections, including Tuberculosis whose transmission is predominantly domestic, and sexually transmitted infections including HIV. Interventions varying in purpose will be chosen from a range of possibilities on an evidence-based basis, by groups comprising the residents themselves, with a special focus on youths, facilitated by our team. Work will be based in 3 urban slum communities where we have already collected and analyzed data on a range of communicable diseases, having established relationships with residents' groups, fully and enthusiastically committed to the program. We will evaluate changes in incidence rates for diseases before, during and after interventions, as well as data on multiple aspects of knowledge, attitudes and practices of residents, environmental data in public, peri-domestic, and domestic areas, the presence, extent and location of open sewers and trash accumulation, and relevant water/soil samples to quantify pathogen loads. At the beginning of the project, in each community, a working group of residents and experts will be established, who will critically evaluate current findings to identify and guide acquisition of additional data required to choose interventions. Thus, over the first year, each community will use the previously- and newly-collected data as a basis for defining key interventions and relevant metrics to evaluate the interventions. Further pre-intervention metrics will be collected during the second 6 months. Then, at the end of the first year, community-specific interventions will be implemented - either environmental (eg closing sewers) or behavioural (eg improving access to health visitors), following which further data will be collected. After a further 9 months, the management groups will undertake an evidence-based assessment of the interventions' effectiveness, reflecting on the outcomes. This will lead to a re-considered, modified, set of interventions (or a decision to maintain the status quo), followed by further data collection, and ultimately to a full assessment of both the interventions, and of the processes that led to their initial genesis and subsequent adaptation.",,2021,N/A,2681972.38,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Zika virus disease | Other,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Community engagement | Indirect health impacts | Social impacts,2021 +P27001,GB-GOV-13-FUND--GCRF-EP_T003650_1,Mathematical Modelling for Infectious Disease Dynamics and Control in East Africa (MMIDD-EA),"Computer-based mathematical modelling of infectious diseases is an essential tool to understanding how diseases spread. They can also be extremely useful in designing effective control strategies and policies. The East Africa region is a hotspot for emerging and endemic diseases caused by bacteria and viruses, including those spread from animals to humans (known as zoonoses). Despite the potential for mathematical modelling to address public health challenges in the region and the availability of relatively cheap computing power and free programming platforms, these skills are rarely applied by academics and researchers in low and middle income countries. Instead modelling work is done by researchers from high income countries and often for diseases threatening global health such as epidemics caused by the Ebola virus. We aim to develop a network of East-African based mathematical modellers to build skills and capacity so that this work can be performed for priority infectious diseases in the region and by local researchers, who have a superior understanding of the social, economic, geographic and political context of infectious disease spread and control. To do this we will organise three activities. First, we will develop and run an intensive short-course in mathematical modelling of infectious disease dynamics for 20 people in Kenya. Applications will be sought from researchers based in East Africa with skills in mathematics and an interest in quantitative approaches to infectious disease dynamics and control in humans and animals. A competitive selection procedure will prioritise candidates with both institutional support and defined modelling projects relevant to the region to carry forward. The course will be based upon the well-established and highly regarded Mathematical Modelling of Infectious Disease Dynamics residential course supported by the Wellcome Trust, led Dr Andrew Conlan (University of Cambridge) and modified to be appropriate to the needs identified in East Africa. The course will have a strong emphasis on building practical skills using the free software R and Rstudio, and focussed on infectious diseases that are important in the region. Second, five fellowships will be awarded to course attendees to enable them to further develop their skills. Each fellow will be matched to a mentor from the University of Cambridge or the broader course faculty (drawn from across the UK and Africa) who will work with them to develop their skills and collaborate on a selected modelling projects. The fellows will have the opportunity to spend up to 3 months in Cambridge (or other UK Institute, as befits their project and development needs) as well as the opportunity to spend time at the University of Nairobi and interact with their cohort. Third, we will support the development of an East African infectious disease modelling network, by linking with other complementary initiatives in the region. This will increase the self-reliance of the cohort and help to sustain further capacity building.",,2020,N/A,250529.97,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P27026,GB-CHC-220949-P8890,Sri Lanka Complex Emergency,"An economic crisis in Sri Lanka, which has been developing since March 2020 during the COVID-19 pandemic, has sparked civil unrest and food insecurity. The pandemic, with all its containment measures, resulted in the rapid decline in foreign currency income primarily through Sri Lanka√¢'Ǩ'Ñ¢s adversely impacted tourism sector, worker and diaspora remittances, foreign direct investment (FDI) flows and world trade √Ç Household access to food, fuels, medicines, as well livelihoods and as the provision of education, have all been affected, and there is severe civil unrest and protests across the country.√Ç The IFRC have launched an appeal for 28 million CHF, to support 500,000 people over the next 12 months√Ç",,2022,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P27035,GB-CHC-220949-P8568,Afghanistan Crisis 2021,"Afghanistan is reeling from a complex humanitarian crisis resulting from compounding impacts of conflict, drought, food insecurity and displacement as well as gaps in health services. A recent escalation in the conflict has created additional stress and unpredictability to the country and population, rapidly increasing the number of displaced people. The escalation of conflict occurred in the backdrop of a drought that has affected more than 80 per cent of the country. In a drought declaration by the government on 22 June 2021, the country√¢'Ǩ'Ñ¢s wheat crop will be reduced by nearly two million tons. Additionally, more than three million livestock are in danger of perishing due to a lack of fodder and water. The winter season will start in October with a potential for severe impact on drought-affected and displaced people whose coping capacities are already weakened. The compounding impacts of drought and conflict which escalated in July and the first half of August have exacerbated the hard living conditions in a country that is also grappling with COVID-19 and poverty. Amid several surges in COVID19 cases, the socio-economic impacts of the pandemic will continue to be felt, with the continued risk of new waves. Affected people are reliant on aid, including food assistance, lifesaving health care, and means to restore and protect their livelihoods. As of early August, around 11 million people are experiencing high levels of acute food insecurity due to the combination of conflict, COVID-19, high food prices, and rampant unemployment1 . These numbers are likely to increase due to developments of recent weeks though data is yet to be confirmed as the situation is evolving IFRC has revised Emergency Appeal seeks 36 million Swiss francs, increased from 15 million Swiss francs, to scale up the Afghan Red Crescent Society (ARCS) humanitarian response for addressing needs wrought by multiple humanitarian crises in Afghanistan. The country is experiencing compounding effects of drought, conflict, displacement and gaps in health services, as well as anticipating a harsh winter. This Emergency Appeal will enable the International Federation of Red Cross and Red Crescent Societies (IFRC) to support the ARCS to deliver assistance and support to 560,000 people over 24 months. In addition to increasing the number of people to be assisted, this revised Emergency Appeal extends the operation timeframe and expands the geographic scope. With this revision, there is a funding gap of CHF 35,150,000 Swiss francs.",,2021,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P27036,GB-CHC-220949-P8744,In-country Afghanistan Crisis 2021,"Afghanistan is reeling from a complex humanitarian crisis resulting from compounding impacts of conflict, drought, food insecurity and displacement as well as gaps in health services. A recent escalation in the conflict has created additional stress and unpredictability to the country and population, rapidly increasing the number of displaced people. The escalation of conflict occurred in the backdrop of a drought that has affected more than 80 per cent of the country. In a drought declaration by the government on 22 June 2021, the country√¢'Ǩ'Ñ¢s wheat crop will be reduced by nearly two million tons. Additionally, more than three million livestock are in danger of perishing due to a lack of fodder and water. The winter season will start in October with a potential for severe impact on drought-affected and displaced people whose coping capacities are already weakened. The compounding impacts of drought and conflict which escalated in July and the first half of August have exacerbated the hard living conditions in a country that is also grappling with COVID-19 and poverty. Amid several surges in COVID19 cases, the socio-economic impacts of the pandemic will continue to be felt, with the continued risk of new waves. Affected people are reliant on aid, including food assistance, lifesaving health care, and means to restore and protect their livelihoods. As of early August, around 11 million people are experiencing high levels of acute food insecurity due to the combination of conflict, COVID-19, high food prices, and rampant unemployment1 . These numbers are likely to increase due to developments of recent weeks though data is yet to be confirmed as the situation is evolving √Ç IFRC has revised Emergency Appeal again, seeks 90 million Swiss francs, to scale up the Afghan Red Crescent Society (ARCS) humanitarian response for addressing needs wrought by multiple humanitarian crises in Afghanistan. The country is experiencing compounding effects of drought, conflict, displacement and gaps in health services, as well as anticipating a harsh winter and the recent Earthquake in June 2022. This Emergency Appeal will enable the International Federation of Red Cross and Red Crescent Societies (IFRC) to support the ARCS to deliver assistance and support to 1.1million people over 36 months. In addition to increasing the number of people to be assisted, this revised Emergency Appeal extends the operation timeframe and expands the geographic scope",,2021,N/A,41676881.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P27037,GB-CHC-220949-P8745,Regional Afghanistan Crisis 2021,"Afghanistan is reeling from a complex humanitarian crisis resulting from compounding impacts of conflict, drought, food insecurity and displacement as well as gaps in health services. A recent escalation in the conflict has created additional stress and unpredictability to the country and population, rapidly increasing the number of displaced people. The escalation of conflict occurred in the backdrop of a drought that has affected more than 80 per cent of the country. In a drought declaration by the government on 22 June 2021, the country√¢'Ǩ'Ñ¢s wheat crop will be reduced by nearly two million tons. Additionally, more than three million livestock are in danger of perishing due to a lack of fodder and water. The winter season will start in October with a potential for severe impact on drought-affected and displaced people whose coping capacities are already weakened. The compounding impacts of drought and conflict which escalated in July and the first half of August have exacerbated the hard living conditions in a country that is also grappling with COVID-19 and poverty. Amid several surges in COVID19 cases, the socio-economic impacts of the pandemic will continue to be felt, with the continued risk of new waves. Affected people are reliant on aid, including food assistance, lifesaving health care, and means to restore and protect their livelihoods. As of early August, around 11 million people are experiencing high levels of acute food insecurity due to the combination of conflict, COVID-19, high food prices, and rampant unemployment1 . These numbers are likely to increase due to developments of recent weeks though data is yet to be confirmed as the situation is evolving IFRC has revised Emergency Appeal seeks 36 million Swiss francs, increased from 15 million Swiss francs, to scale up the Afghan Red Crescent Society (ARCS) humanitarian response for addressing needs wrought by multiple humanitarian crises in Afghanistan. The country is experiencing compounding effects of drought, conflict, displacement and gaps in health services, as well as anticipating a harsh winter. This Emergency Appeal will enable the International Federation of Red Cross and Red Crescent Societies (IFRC) to support the ARCS to deliver assistance and support to 560,000 people over 24 months. In addition to increasing the number of people to be assisted, this revised Emergency Appeal extends the operation timeframe and expands the geographic scope. With this revision, there is a funding gap of CHF 35,150,000 Swiss francs.",,2021,N/A,41667388.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P27091,GB-CHC-292506-GB1G6,Women Lead in Emergencies in Tigray Ethiopia - Phase 2,"The Women'Äôs Leadership in Recovery, Peace & Security in Tigray & Afar, Ethiopia, is the second phase of WLiE project, scheduled to begin in April 2024 and will conclude in March 2027. The primary goal of the project is empowering women and girls in Tigray and Afar by addressing conflict trauma, promoting economic stability, and involving them in humanitarian and peace efforts. It also focuses on preventing Gender-Based Violence (GBV) through community engagement and transformative approaches involving men to support women's leadership and participation",,2024,N/A,3572330.54,Human Populations,Unspecified,Unspecified,Unspecified,Women | Other,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2024 +P27100,XM-DAC-41122-Colombia-0930/A0/06/880/008,COVID-19 RESPONSE,"New Element, which contributes to Other Cross-Sectoral Programme Areas, Other Cross-Sectoral Programme Areas (Covid). UNICEF aims to achieve this through Operational Support To Programme Delivery, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: Country programmes are efficiently designed, coordinated, managed and supported to meet quality programming standards in achieving results for children",,2020,N/A,37121.03,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27124,GB-CHC-292506-GB863,Women lead in Emergencies: Strengthening GBV response in Tigray,"FCDO is looking to give 1mil over 2 years to CARE for an accountable grant to reduce GBV in the Tigray region. This is likely to include funding for one stop shop centres, work around norms changing, and working with local partners (Women's Association of Tigray) on community mobilization, psychosocial support and awareness raising.",,2022,N/A,1611220,Human Populations,Unspecified,Unspecified,Unspecified,Women | Other,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +P27173,XM-DAC-41302-IP22-NPL828,The government and social partners have promoted fundamental principles and rights at work to protect workers especially from unacceptable forms of work,The government and social partners have promoted fundamental principles and rights at work to protect workers especially from unacceptable forms of work,,2022,N/A,2154357.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Unspecified,,,,,,,,,Unspecified,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2022 +P27214,XM-DAC-47066-IS.0064,"Engage, Connect, Empower: Building Resilience through Integrated Action of Dynamic Youth and Local Government for the Environment (BRIDGE)","The project aims to address the critical gap in public life participation of youth that compromises their communities'Äô cohesiveness and capacity to withstand current and potential future social and economic shocks in a country already severely impacted by a weak economy, lack of opportunities, scarcely efficient social services and precarious social safety-nets, as well as high rates of emigration and return migration, all further exacerbated by the consequences of the COVID-19 pandemic. In tackling these challenges through its 'ÄúEngage, Connect, Empower'Äù approach, IOM seeks to strengthen youth in Ukraine to bring about cohesion and resilience in their communities. In doing so, the action anticipates that 1) youth, youth-focused organisations and authorities will increase their engagement in community action; 2) they will have enhanced connections across Ukraine; and 3) youth will be empowered to be drivers of change in their communities.",,2021,N/A,541794.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts | Economic impacts,2021 +P27248,GB-CHC-1148404-DK-CVR-20699310-DF21849,Healthier info-ecosystems for healthier people,"The focus of the Internews H2H-intervention is to enable more reality- and demand-driven communication across the region in all issues emerging from and related to the COVID-19-response. Based on expertise gained during previous health-emergencies and building on the Misinformation Management methodologies, Internews aims to increase trust in and therefore traction of reliable and locally relevant information, by connecting data-collection and monitoring activities (including social media monitoring, rumour tracking and community engagement activities by Internews and others), with the latest vetted information coming from health experts and agencies and using its media and social-media expertise to provide information packages that combine both in a format that enables local media to create content that is best fit for their outlet, channel and audience, in the language they like and understand.",,2020,N/A,243423.65,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Communication,2020 +P27253,GB-COH-02651349-20186-347,Hygiene and Behaviour Change Coalition (HBCC) 'Äì Vaccine Data Co-Lab,"The Vaccine Data CoLab is the result of COVIDaction extending the pathway of what'Äôs possible; beyond supporting the scaling of new innovations and technology applications working with a range of partners. This next phase will be a collaboration that will build on the experience of Frontier Tech Hub COVIDaction work but work in partnership with the partners under the FCDOs Hygiene and Behaviour Change, HBCC2, programme. It will also focus longer term on providing technical expertise and innovation to support building resilience of systems and preparedness for future pandemics. The Vaccine Data Co-Lab is a component of the FCDO and Unilever'Äôs Hygiene and Behaviour Change (HBCC 2) programme. The objective of the Vaccine Data CoLab is to extend reach by continuing the COVIDaction partnership with COVAX GIS/ WHO, but extending this to include partners such as the London School of Hygiene (LSHTM) under HBCC2 programme, exploring the key question of we can increase vaccine uptake amongst the most vulnerable 'Äì for COVID and other vaccinations 'Äì by using hyperlocal data driven? The Co-lab will provide broad responsive global support to the HBCC 2 on how to better use data for behaviour change (particularly vaccine hesitancy) as well engaging with two country programmes ( Nigeria and one other tbc) where FCDO work with governments, donors, and their implementing partners assess the current data ecosystem available to address vaccine demand, design targeted activities and grants to address key niche areas, and train and build hyperlocal data analysis capacity in country leveraging our partnership with the COVAX GIS working group. The Vaccine Data CoLab (VDC) is a pivot of the original Data Challenge established by COVIDaction in May 2020, to identify and support global social data goods that could help different LMIC actors (including other donors, governments, academics, NGOs, and the private sector) access and use data they needed to address COVID-19. As vaccines were approved and rolled out by COVAX and other partners, the Vaccine Data CoLab was set up to invest in data tools and approaches to inform the equitable distribution of vaccines within specific countries. The VDCL focused on bridging the gap between countries'Äô data needs, existing data systems, and potentially appropriate technologies, through funding local collaborations and global sharing of 'Äòwhat works'Äô. One year later, the Vaccine Data CoLab has supported the use of data to inform vaccine distribution and address hesitancy and misinformation across Senegal, Vietnam, Nigeria. The VDCL has built a coalition with COVAX GIS Working Group, supporting their mission to build capacity in LMICs to use and apply GIS microplanning data tools & approaches for equitable vaccine uptake. This partnership will continue and expand into the next phase. Whilst the original focus of the VDCL was on data for vaccine prioritisation (supply), this next phase will focus on misinformation and vaccine hesitancy (demand), which are proving equally important as a bottleneck in the vaccine uptake. Vaccine hesitancy is specific to sub-groups within populations and is rarely population wide.",,2022,N/A,1168228.73,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2022 +P27255,GB-CHC-290767-RAPID,Rwandan Answer to Pandemic through Investment and Development (RAPID),"The project will strive to mitigate health as well as economic and social impacts of COVID'Äë19. It will adopt a youth-led approach. Given that the median age of the continent is 19.7 years, youth leadership will be critical for prevention and containment activities (World Economic Forum, 30/03/20). SACCA will build on its 5-years'Äô experience of training young people and extensive community links, and establish a community-based structure of 38 RAPID facilitators supported by 141 village communicators. Facilitators will be recruited from SACCA'Äôs graduates who lost employment and other active youth. They will work closely with sector and cell leaders and identify 'Äúat-risk'Äù groups to the virus and lockdown aftershocks (older people, people with disabilities, informal workers, vulnerable families etc.). The facilitators will support more than 5,000 households (at least 20,000 individuals) to adopt preventative behaviours to protect themselves and others from COVID'Äë19. They will train community members in hand-washing and deliver accurate messages as well as leaflets about the disease. The facilitators will be able to address the cultural and social factors around risk perception and risk management. They will ensure that their message does not increase stigma and does not deter people from reporting symptoms and seeking treatment. If facilitators come across cases that require psycho-social or other support, they will refer those to SACCA'Äôs professional staff. Facilitators will distribute hygiene kits in line with WASH standards to 1,000 vulnerable households. These households will also receive masks made by a group of tailors with hearing impairments. They will also identify 300 the most at-risk individuals (elderly and those with comorbidities). The project will provide them with simple hand-washing station. The facilitators will promote a stay-at-home option while helping this group with food delivery in line with updated government'Äôs guidelines (¬£21 per family of 4). We will also aim to support 675 vulnerable people who are the most affected by the aftermath of the lockdown (informal workers, families with large number of children etc.). In addition to information, during first 3 months, these households will be supported with cash transfers in line with government'Äôs guidelines. During the following 3 months, when some informal workers will be able to restart paid work, the support will focus on 120 households to enable them to engage in subsistence agriculture. The facilitators will also signpost any available resources from the government or other organisations. The project will further complement the Government'Äôs efforts to raise community awareness on COVID-19 and hygiene behaviours with a strong focus on the hard to reach population. It will also support 45 additional street girls in SACCA Rehabilitation Centre. It will also deliver essential hand-washing and other equipment to 15 health centres and 28 health posts in Kayonza District.",,2020,N/A,252479.96,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +P27306,GB-GOV-13-FUND--GCRF-MR_T02996X_1,Responding to the challenge of MERS-CoV: Development and testing of interventions to reduce risk among Bedouin populations in Southern Jordan,"Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a recently identified 'emerging infectious disease' first seen in Jordan and Saudi Arabia in 2012. Clinical cases can present as a sudden acute respiratory infection, with rapid onset pneumonia and death, although milder infections also occur (in some cases without any symptoms at all). Since the initial outbreaks in 2012, there have been almost 2500 confirmed cases, with over a third of those infected subsequently dying from the disease (848 people to date). Confirmed cases have been reported across 27 countries, although the majority have been in the Arabian Peninsula, with Saudi Arabia the disease epicentre (over 80% of all confirmed cases). Primary infection in humans occurs through contact with infected dromedary camels (or camel products) and camel populations act as the host reservoir for the virus, however infection in camels causes only mild symptoms, similar to a common cold (and may cause no symptoms at all). Once someone becomes infected in this way secondary human-to-human transmission of the virus can then occur (often in a hospital setting) with the potential to cause large scale outbreaks such as those seen in South Korea and Saudi Arabia in recent years. Jordan's strategic location at the centre of current Middle Eastern crises means that its stability within the region is of global significance. Enormous influxes of displaced peoples into Jordan from the conflicts in Syria, Iraq and Yemen among others (accounting for over 30% of the population) have placed unprecedented demands on Jordan's national disease surveillance, response and health-care services and increased the risk of catastrophic disease outbreaks occurring in the future, including MERS-CoV. Jordan's long, porous border with Saudi Arabia, across which frequent movements of people and livestock occur (particularly among rural Bedouin populations in the south of the country) and large camel populations, mean that the risks posed by MERS-CoV remain high. The World Health Organization (WHO) have designated MERS-CoV to be a Blueprint Priority Disease for Research and Development, alongside other 'emerging infectious diseases' that represent a potential global threat, including Ebola, Lassa and Nipah viruses. The development of vaccines against MERS-CoV, for use in both camels and humans, is already at an advanced stage, however knowledge regarding the diseases epidemiology and cultural context (which are essential for effective vaccine deployment) is currently lacking. A similar lack of knowledge has delayed the deployment of other vaccines in the past (e.g. recently the Lassa virus vaccine in West Africa) and so it is important that deployment of future MERS-CoV vaccines is not delayed for the same reasons. It is crucial therefore that appropriate research be conducted among high-risk populations. With this in mind, and building on the findings of successful GRCF Foundation Award research, we aim to conduct state-of-the-art interdisciplinary research to determine the biological and sociocultural contexts of the disease among at-risk Bedouin populations in southern Jordan. In particular, we are seeking to understand which individuals, or camels, should be targeted for future vaccination, the correct seasons for the deployment of such vaccines and the sociocultural issues that are driving the infection, with consideration of these sociocultural issues vital when looking at potential control measures for the disease, including vaccination. Through this project we thus aim to develop appropriate, community based behavioural interventions that will reduce the risk of infection among these communities (as well as considering the potential role of vaccines in the future). We are also aiming to build Jordan's capacity for strategic research, surveillance and control activities to confront the challenge posed by MERS-CoV (as well as by other 'emerging infectious diseases').",,2021,N/A,2654740.21,Animals | Human Populations,Other,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV),"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Community engagement,2021 +P27328,GB-GOV-13-FUND--GCRF-MR_V033530_1,Household Transmission and Immunity to SARS-CoV-2 among Paediatric Clients of a Primary Care Center in a Low-resource Community in Rio de Janeiro,"MRC GECO COVID award to study the household transmission dynamics of SARS-CoV-2 in a slum in Rio de Janeiro, Brazil and to estimate the immunity of the study population against the new virus.",,2020,N/A,738745.48,Human Populations,Unspecified,Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease transmission dynamics,2020 +P27329,XM-DAC-41114-PROJECT-00130542,Strengthening COVID-19 Recovery and Resilient Livelihood,Strengthening COVID-19 Recovery and Resilient Livelihoods in Myanmar as a consequence of the COVID-19 pandemic.,,2020,N/A,9599051.61,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P27330,DK-CVR-20699310-DRCRO01-19,DRC COVID-19 Global Appeal East Africa and Great Lakes Region,"DRC is present in 9 countries in the East Africa and Great Lakes Region. DRC has implemented COVID-19 specific activities in all of these countries: Burundi, Central African Republic, Djibouti, DR Congo, Ethiopia, Kenya, Somalia, Tanzania, Uganda, & South Sudan The East Africa and Great Lakes region represents DRC's largest engagement in terms of number of countries and outreach focusing on addressing COVID-19-related impact on conflict- and displacement affected populations. In the region, nine DRC country offices reported COVID-19 response programmes, reaching close to 2,5 million people in 2020 .",,2020,N/A,613778514.6,Human Populations,Black,Unspecified,Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P27331,XM-DAC-41114-PROJECT-00127475,Support to COVID-19 Response,COVID-19 Response Plan for Nigeria with the objective to ensure optimum care of confirmed COVID-19 cases and contain the spread of the outbreak through an inclusive and nationally owned process and based on emerging best practices.,,2020,N/A,87343682.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Clinical characterisation and management | Infection prevention and control,"Supportive care, processes of care and management",2020 +P27332,XM-DAC-41114-PROJECT-00131629,RFF Post COVID-19,"The project aims to accelerate the post COVID-19 transition to a circular economy, focusing on the recovery of low-value glass, plastic and paper waste streams, in Samoa & Tokelau, while enhancing youth employment.",,2020,N/A,1023929.52,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P27333,XM-DAC-41122-Bangladesh-5070/A0/05/106/004,6.04 EDUCATION COVID-19 RESPONSE,"106/004 Governments and partners have increased capacity to provide continued access to Education services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level, which contributes to Cross-Sectoral Communication For Development, Cross-Sectoral Communication For Development (Covid), Equitable Access To Quality Education, Equitable Access To Quality Education (Covid), Learning Outcomes, Learning Outcomes (Covid). UNICEF aims to achieve this through Evaluations, Research And Data, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,633396.64,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Internally Displaced and Migrants | Women | Minority communities unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27334,XM-DAC-41122-Bangladesh-5070/A0/05/106/008,6.08 CAP COVID-19 RESPONSE,"106/008 The general public has increased capacity to prevent and respond to COVID-19 infection in order to suppress COVID-19 transmission at community level, which contributes to Cross-Sectoral Communication For Development, Cross-Sectoral Communication For Development (Covid). UNICEF aims to achieve this through Evaluations, Research And Data, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,707022.57,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27335,XM-DAC-41122-Bangladesh-5070/A0/05/106/005,6.05 CHILD PROTECTION COVID-19 RESPONSE,"106/005 Governments and partners have increased capacity to provide continued access to Child Protection services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level, which contributes to Access To Justice, Access To Justice (Covid), Adolescent Empowerment, Adolescent Empowerment (Covid), Children With Disabilities, Cross-Sectoral Communication For Development, Gender Discriminatory Roles And Practices, Harmful Practices (Fgm/C And Child Marriage), Prevention And Response Services For Violence Against Children, Prevention And Response Services For Violence Against Children (Covid), Social Protection, Social Protection (Covid). UNICEF aims to achieve this through Advocacy And Public Engagement, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,5923411.26,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Women,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27336,XM-DAC-41122-Bangladesh-5070/A0/05/106/012,6.12 OPERATIONS COVID-19 RESPONSE,"106/012 Governments and partners have increased capacity to provide continued access to Operations services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level, which contributes to Operations Support To Programme Delivery, Operations Support To Programme Delivery (Covid), Supply And Logistics, Supply And Logistics (Covid). UNICEF aims to achieve this through Operational Support To Programme Delivery. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,2581842.24,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27337,GB-GOV-3-IP_FDEAC19,COVID-19 related Frontline Diplomatic Enabling Activity,Assistance in line with UK objectives on diplomatic activity which supports in tackling COVID-19,,2020,N/A,18758411.5,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27338,XM-DAC-41122-Bangladesh-5070/A0/05/106/001,6.01 HEALTH COVID-19 RESPONSE,"106/001 Governments and partners have increased capacity to provide continued access to Health services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level, which contributes to Child Health, Child Health (Covid), Immunization, Maternal And Newborn Health, Maternal And Newborn Health (Covid). UNICEF aims to achieve this through Evaluations, Research And Data, Operational Support To Programme Delivery, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,27514616.07,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year),Unspecified,Internally Displaced and Migrants,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27339,GB-GOV-1-301188,Accelerated Covid 19 Economic Support (ACES),Immediate draw down services for coordinated economic response by African governments. The offer includes technical assistance and analytical capability on how to manage the COVID-19 crisis from a multi-disciplinary perspective with a focus on delivery capability of Coordination Units and Central Crisis Units.,,2020,N/A,8035688.51,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P27341,XM-DAC-41122-Bangladesh-5070/A0/05/106/003,"6.03 Water, Sanitation, and Hygiene (WASH) COVID-19 RESPONSE","106/003 Governments and partners have increased capacity to provide continued access to Water, Sanitation, and Hygiene (WASH) services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level., which contributes to Sanitation, Sanitation (Covid), Water, Water (Covid). UNICEF aims to achieve this through Operational Support To Programme Delivery, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,8656791.85,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Internally Displaced and Migrants | Women,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts | Social impacts,2020 +P27342,GB-CHC-207544-94303,COVID-19 DID Covid Response Nigeria,This task order addresses accessibility of centres where people autonomously go to get tested for COVID-19; isolation and treatment units (excluding intensive care facilities); and any other relevant infrastructure identified during the planning process,,2020,N/A,28557345.15,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Health service delivery,2020 +P27343,XM-DAC-41122-Bangladesh-5070/A0/05/106/006,6.06 Communication for Development (C4D) COVID-19 RESPONSE,"106/006 Governments and partners have increased capacity to provide continued access to Communication for Development (C4D) services and critical supplies for women and children for strengthening Infection Prevention and Control and for suppressing the COVID-19 transmission at community level, which contributes to Cross-Sectoral Communication For Development, Cross-Sectoral Communication For Development (Covid), Evaluation And Research, Evaluation And Research (Covid). UNICEF aims to achieve this through Advocacy And Public Engagement, Evaluations, Research And Data, Fostering Innovation And Use Of New Technologies, Systems Strengthening And Institution Building. This contributes to the following Country Programme result: 6. By 2022, children and women have equitable access to knowledge and services related to COVID-19 prevention and treatment in the areas of health, nutrition, education, Water, Sanitation, and Hygiene (WASH) and child protection in the most deprived areas, including Rohingya refugee camps.",,2020,N/A,3529922.93,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Community engagement | Indirect health impacts | Social impacts,2020 +P27344,GB-CHC-207544-96000ASC2000,COVID-19 ASCEND Sightsavers - Liberia,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58386328.99,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27345,GB-CHC-207544-95100ASC2000,COVID-19 ASCEND Sightsavers - Benin,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58491926.99,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27346,GB-CHC-207544-96200ASC2000,COVID-19 ASCEND Sightsavers - Nigeria,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,57908642.79,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27347,XM-DAC-41122-India-2040/A0/06/400/404,404 PROVIDE PROTECTION SERVICES FOR CHILDREN & ADOLESCENTS DURING COVID-19,"Governments and partners have increased capacity to provide critical protection services for children and adolescents, in response to the COVID outbreak., which contributes to Access To Inclusive Social Protection, Access To Inclusive Social Protection (Covid), Learning, Skills, Participation And Engagement, Learning, Skills, Participation And Engagement (Covid), Promotion Of Care, Mental Health And Psychosocial Well-Being And Justice, Promotion Of Care, Mental Health And Psychosocial Well-Being And Justice (Covid), Protection From Violence, Exploitation, Abuse And Neglect, Protection From Violence, Exploitation, Abuse And Neglect (Covid). UNICEF aims to achieve this through Advocacy And Public Engagement, Community Engagement, Social And Behaviour Change, Data, Research, Evaluation And Knowledge Management, Developing And Leveraging Resources And Partnerships, Evaluations, Research And Data, Fostering Innovation And Use Of New Technologies, Harnessing Power Of Business And Markets, Systems Strengthening And Institution Building, Systems Strengthening To Leave No One Behind, United Nations Working Together. This contributes to the following Country Programme result: Business and Key Business Stakeholders demonstrate growing willingness, commitment and resource allocation for protecting and promoting child rights in policy and practice by 2022",,2020,N/A,7220948.76,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Community engagement | Indirect health impacts | Social impacts | Health information systems,2020 +P27348,GB-CHC-207544-95700ASC2000,COVID-19 ASCEND Sightsavers - Ghana,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58511370.86,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27349,GB-CHC-207544-95800ASC2000,COVID-19 ASCEND Sightsavers - Guinea,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58258641.03,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27350,GB-CHC-207544-96300ASC2000,COVID-19 ASCEND Sightsavers - Sierra Leone,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58275020.5,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27351,GB-CHC-207544-96703ASC2000,COVID-19 ASCEND M&C Saatchi,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,55234862.91,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27353,GB-CHC-207544-95602ASC2000,COVID-19 ASCEND EG LSTM - DRC,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58444367.4,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27354,GB-CHC-207544-95900ASC2000,COVID-19 ASCEND Sightsavers - Guinea Bissau,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58612829.83,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27355,GB-CHC-207544-95401ASC2000,COVID-19 ASCEND non-Sightsavers - Chad,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58494205.05,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27356,GB-CHC-207544-95202ASC2000,COVID-19 ASCEND EG LSTM - BKF,COVID-19 response work carried out through a repurposed portion of ASCEND programme activity.,,2020,N/A,58612958.63,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27357,GB-CHC-207544-24032COVID19,COVID-19 Boresha Macho Inclusive Eye Health Project,COVID-19 response work carried out under UKAM project in Tanzania,,2020,N/A,2902.14,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27358,GB-CHC-207544-95503ASC2000,COVID-19 ASCEND EG SCI - CIV,COVID-19 response work carried out through repurposed ASCEND programme activity.,,2020,N/A,58325150.11,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27359,GB-CHC-207544-75069COVID19,COVID-19 The right to Health:Breaking down barriers to EH,COVID-19 response work carried out under project in Pakistan,,2020,N/A,5505.17,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27361,XM-DAC-41122-India-2040/A0/06/300/305,305 COVID - IPS HAVE THE CAPACITY TO STRENGTHEN INFECTION PREVENTION & CONTROL,"Governments and partners have increased capacity to provide critical Water, Sanitation, and Hygiene (WASH) supplies and services and strengthen Infection Prevention and Control in communities and institutions., which contributes to Safe And Equitable Water, Sanitation And Hygiene Services And Practices, Safe And Equitable Water, Sanitation And Hygiene Services And Practices (Covid), Water, Sanitation And Hygiene Systems And Empowerment Of Communities, Water, Sanitation And Hygiene Systems And Empowerment Of Communities (Covid). UNICEF aims to achieve this through Community Engagement, Social And Behaviour Change, Data, Research, Evaluation And Knowledge Management, Evaluations, Research And Data, Systems Strengthening And Institution Building, Systems Strengthening To Leave No One Behind. This contributes to the following Country Programme result: Infants, young children, and caregivers especially the most vulnerable have equitable access to and use sustainable, safe, and affordable Water, Sanitation, and Hygiene (WASH) services (including in Institutions) across the lifecycle.",,2020,N/A,4109558.97,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts | Social impacts,2020 +P27362,GB-COH-213890-82604802,COVID response,This is part of the COVID health response with a focus on those affected by the secondary impacts of COVID and maintaining resilience into the monsoon season in order to slow the spread of COVID save lives and reduce suffering and indignity.,,2020,N/A,3356408.27,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P27363,GB-CHC-292506-GB798,DFID (MM) Purnima COVID WASH,"CARE Nepal, as part of our larger COVID-19 response program has planned to implement the Purnima COVID WASH Response initiative to reduced risk of potential COVID 19 outbreak through improved WASH facilities",,2020,N/A,396235.17,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,,2020 +P27364,GB-CHC-220949-P8092,COVID-19 Outbreak,"On 31 December 2019, WHO was alerted to several cases of pneumonia in Wuhan City, Hubei Province of China. This virus was later identified as a new virus and has been named √¢'Ǩ≈ì2019-nCoV.√¢'Ǩ¬ù The new virus is a coronavirus, which is a family of viruses that include the common cold, and viruses such as SARS and MERS. On the 30th January 2020, Coronavirus was declared a public health emergency of international concern by WHO. On the 28th February 2020 the WHO upgraded the global risk from the coronavirus to ""very high."" On the 11th Feb the virus was officially named COVID-19: - The name is taken from the words ""corona"", ""virus"" and ""disease"", 2019 representing the year that it emerged. - The word coronavirus refers to the group of viruses it belongs to, rather than the latest strain. - The virus itself has been designated SARS-CoV-2 by the International Committee on Taxonomy of Viruses. On the 11th March the coronavirus outbreak was labelled a pandemic by WHO.",,2020,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",,2020 +P27365,GB-COH-213890-82604730,COVID-19 response,Part of Save the Children's global response to the COVID-19 outbreak.,,2020,N/A,323335.21,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27367,XI-ROR-RF/ICT/7639-AAIP_EK_001,COVID ELISA kit Project,Developing Low Cost ELISA diagnostic kits for COVID diagnosis (i.e. infection with SARS CoV2 virus),,2021,N/A,168591.33,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P27368,AT-UID-U74408937-H2H_COV_expense_2020,Perceptions of a Pandemic: Strengthening the quality and relevance of the COVID-19 global response through community input,Response wide COVID 'Äì 19 GLOBAL SUPPORT community perception. Communication with and accountability to communities affected by the crisis,,2020,N/A,248283.25,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P27369,XI-ROR-RF/ICT/7639-AAIP_HW_001,COVID HSNIG Nasal Wash Project,Selection of patients suffering from symptoms of COVID within the recent 24 hours,,2021,N/A,47755.03,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2021 +P27370,GB-GOV-13-GCRF-MR_ARE_C19-V83XXLF-B9VAM9V,CVR Coronavirus COVID-19 Supplement,Additional funding in response to the covid-19 outbreak COVID-19,,2020,N/A,653464.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27371,GB-CHC-1047501-DRC-COVID,Democratic Republic of Congo (DRC) COVID-19 Response: Strengthening National Response Plans for COVID-19,Health and WASH provisions to respond to COVID-19 in Kinshasa,,2020,N/A,1854397.47,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,,2020 +P27372,GB-CHC-1166956-90,UK-Med Support to the COVID-19 Response in Yemen,"UK-Med Support to Yemen COVID-19 response June 2020, Yemen Logframe for COVID-19",,2020,N/A,958750.86,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27374,US-EIN-37-1552838-75,Omnivis - COVID-19 pivot,"Addressing the compounding effects of cholera and COVID-19 by expanding water testing sites, as well as partnering with MNOs to facilitate SMS alert notifications to local communities about cholera outbreaks.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27375,NO-BRC-977538319-ACSY2004,ACAPS COVID-19 Analysis Hub (Closed),ACAPS will strive to provide analysis for the humanitarian sector and others to guide the scale-up and reorientation of humanitarian action in response to the COVID-19 pandemic. We will do this through a) providing global and context specific analysis on how Covid-19 is reshaping humanitarian outcomes; b) by connecting and convening analysts strengthening capacities for analysis throughout and beyond the humanitarian sector.,,2020,N/A,364496.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P27376,US-EIN-37-1552838-45,oDoc - Offer online consultation for diagnosing potential COVID-19,Offer online consultation for diagnosing potential COVID-19 patients and helping COVID-19 patients in manage their symptoms. Set up call centers for taking care of non-app user patients through calls. Offer chat bot services and other AI based diagnostic services,,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P27377,GB-CHC-292506-GB794,START Fund COVID 19 Nepal,The project will support the migrant returnees to reach their home destinations safely and to ensure that they communicate information on prevention measures to minimize the risk of COVID-19.,,2020,N/A,120190.42,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Communication,2020 +P27378,GB-GOV-13-GCRF-MR_ARE_C19-V83XXLF-6CAU5YL,Centre for Global Infectious Disease Analysis COVID-19,Additional funding in response to the covid-19 outbreak COVID-19,,2020,N/A,653464.99,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27379,GB-GOV-1-301467,Emergency health assistance to India to respond to COVID-19,"Provision of medical equipment to support the Government of India'Äôs response to COVID-19. The programme will provide oxygen concentrators, ventilators and oxygen generators which will enable vital medical treatment to those suffering from COVID-19 in India.",,2022,N/A,3969914.81,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P27380,US-EIN-37-1552838-74,Solidarites - COVID-19 pivot,"Enhancing the SOLIS Whatsapp bot with machine learning to make conversations with refugees more efficient, provide more accurate answers on a wider range of topics (with a focus on COVID-19) and reduce the need for large group training sessions.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Communication,2020 +P27381,GB-GOV-10-GECO,Global Effort on COVID-19 (GECO) Health Research,The UK Department of Health and Social Care (DHSC) funds outstanding global health research through the National Institute for Health Research (NIHR). The Global Effort on COVID-19 (GECO) Health Research is a cross UK government funding call aiming to support applied health research that will address COVID-19 knowledge gaps in ODA-eligible countries.,,2020,N/A,18238401.36,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Health Systems Research,,2020 +P27382,GB-CHC-1107403-2582,COVID-19 Preparedness and Response in Sudan and South Sudan,The overall objective of the project was to support preparedness and response to primary and secondary impacts of COVID-19 on vulnerable individuals and communities. A two-pronged strategy approach expected to achieve this included i) building capacities of communities and health actors/facilities to prepare and respond to the primary impacts of COVID-19 and ii) strengthening health and markets systems to be responsive to the secondary impacts of COVID 19.,,2020,N/A,4318550.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Health service delivery,2020 +P27383,XM-DAC-301-2-109443-001,COVID-19 Africa Rapid Grant Fund,"The COVID-19 pandemic presents a significant challenge that requires a global response informed by evidence. On the African continent, the Africa Centres for Disease Control and Prevention, the World Health Organization, and the African Union are leading a continental response to COVID-19. At the national level, African governments have launched efforts to promote prevention, diagnosis, and treatment. Public funding agencies and science granting councils are complementing these continental and national efforts by supporting research and research-related activities. This project supports the COVID-19 Africa Rapid Grant Fund, which will support research and science engagement projects across seventeen countries through a competitive, peer-reviewed call for research. The funding opportunity invites African researchers, science communicators, and science advisers to submit proposals on the following topics: the COVID-19 virus in Africa; prevention and control; African health governance systems; socio-cultural dynamics of transmission; science engagement; the impact of COVID-19 on individual and community mental health; and vulnerability. The Fund will support up to ninety projects over a 24-month period with the goal of strengthening the evidence base for mitigating the impact of COVID-19 and future pandemics. Moreover, the Fund will strengthen national and regional capacity to collaborate and respond to future shared challenges. The Africa Rapid Grant Fund was jointly established by IDRC, South Africa'Äôs National Research Foundation and its Department of Science and Innovation, the United Kingdom'Äôs Department for International Development and UK Research and Innovation through the Newton Fund, the Swedish International Development Cooperation Agency, and the Fonds de recherche du Qu√©bec. The fifteen African agencies involved in the Science Granting Councils Initiative in sub-Saharan Africa are providing additional support.",,2020,N/A,3138944.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Policy research and interventions | Indirect health impacts | Social impacts,2020 +P27384,US-EIN-37-1552838-57,United Healtcare Distributors - COVID-19 pivot,"Implementing a COVID-19 response and business continuity plan, increasing distribution points for the UHD battery exchange service and further developing smart battery functionality to improve customer access and safety.",,2020,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P27385,GB-GOV-13-GCRF-MR_ARE_C19-V83XXLF-6VWWU5S,Enhancing National COVID-19 Diagnostic Support Capacity in Uganda,Additional funding to Uganda Unit in response to the covid-19 outbreak COVID-19,,2020,N/A,497486.82,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27386,US-EIN-37-1552838-54,Danish Refugee Council - COVID-19 pivot,"Adapting project roll-out plans to focus on enhancing community readiness for digital services, raising awareness of the DRC water ATM system for future use once COVID-19 restrictions are eased.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27387,GB-GOV-1-301227,Climate Smart Jobs Immediate COVID Response,"Climate Smart Jobs Immediate COVID Response will focus on actions which support Uganda'Äôs private sector, focused around support to the financial sector, including injecting liquidity into key parts of the financial markets.",,2020,N/A,3872472.98,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27388,GB-GOV-1-301163,WHO Lebanon Covid-19 response,"Provide rapid support to the healthcare response to Covid-19, delivering much needed medical equipment and supporting public communications through WHO delivery. Assistance would be directed towards quickly stabilising the fragile healthcare system - which was already overburdened and strained by an economic crisis - at a very crucial time. On top of the underlying pressures, the Government has said the crisis is overwhelming the system. This will be both humanitarian and preventive in nature. WHO assess a significant number of lives could be saved if a severe Covid-19 outbreak can be avoided through proper containment measures; it will also mitigate against secondary instability shocks (particularly amongst vulnerable communities such as Syrian and Palestinian refugees).",,2020,N/A,417230.91,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2020 +P27389,GB-GOV-13-FUND--GCRF-MR_V036157_1,CARE: COVID-19 and Antimicrobial Resistance in East-Africa 'Äì impact and response,MRC GECO COVID a program of research in Uganda and Tanzania to investigate the extent to which COVID-19 has changed health-seeking behaviour for common bacterial illnesses and the availability and usage of Abs COVID-19,,2020,N/A,1220903.7,Bacteria | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27390,GB-GOV-1-301207,COVID-19 Emergency Education Response (CEER),"This programme proposes investing ¬£20.5m to offer emergency support to mitigate the immediate impact of the COVID-19 pandemic on education. This will be particularly important for the most marginalised children, including girls and children affected by crisis, who are at risk of dropping out of school entirely due to the pandemic. The investment will support three components. 1. targeted back to school outreach to the most marginalised girls 2. support to countries to develop Accelerated Education Programmes for disadvantaged children whose education has been interrupted by COVID-19 and 3. support for teachers in refugee areas to provide essential education and community outreach where there is extreme need.",,2020,N/A,7225783.2,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P27391,GB-GOV-13-FUND--GCRF-MR_V028650_1,Understanding the Impact of COVID-19 on the Mental Health of Peruvian Older Adults.,MRC GECO COVID award in understanding the impact of COVID-19 on the mental health of Peruvian Older Adults COVID-19,,2020,N/A,58058.6,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27392,US-EIN-37-1552838-60,International Rescue Commitee - COVID-19 pivot,"In response to the rise of gender-based violence (GBV) during the COVID-19 pandemic, replicating and expanding Cu√©ntaNos to support women, girls, survivors of GBV and the LGBTQI community in Guatemala, providing critical information and access to key services.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Sexual and gender minorities | Women | Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Gender,,,,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Social impacts | Communication,2020 +P27394,GB-GOV-1-300981,"COVID-19 learning, evidence and research programme for Bangladesh (CLEAR)","CLEAR will deliver research and evidence on the impacts of the COVID-19 pandemic on individuals, communities and governance.",,2021,N/A,3546266.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2021 +P27395,GB-COH-RC000749-DWIN-MFI56-002,Responding to livelihood impacts of COVID-19 in the Northern Philippines,This grant is awarded to augment existing livelihood work in the context of COVID-19,,2021,N/A,32605.36,Unspecified,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2021 +P27396,DK-CVR-20699310-DF212197,H2H COVID-19 Response,"This activity (Supporting the Humanitarian to Humanitarian network in tackling disinformation related to Covid-19 in Africa and Asia) is a component of Coronavirus Outbreak - UK Response reported by DFID , with a funding type of 'Not for profit organisation' and a budget of ¬£2,000,000. This component benefits Developing countries, unspecified, and works in the following sector(s): Infectious disease control.",,2020,N/A,2429979.92,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Communication,2020 +P27398,GB-GOV-13-GCRF-MR-C-GU-UgPC-20010,Enhancing the Unit Support of Uganda's Efforts to contain COVID-19,MRC GCRF COVID-19 additional funding for the MRC/UVRI and LSHTM research unit uganda for diagnositc support caacity COVID-19,,2020,N/A,1438453.04,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27399,GB-CHC-292506-GB817,Reduce the impact of Covid on girls' education and professional learning,"To address the needs of young adolescent girls who have been prone to school drop-outs, early marriages and GBV due to the impact of COVID-19, CARE will be targeting the parents of a total of 2,500 girls to benefit from cash transfers with the aim to keep them in school. In addition, CARE will provide awareness raising on COVID-19 mitigation and prevention, and implications on school dropouts.",,2020,N/A,107777.85,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Women,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P27400,GB-CHC-1082565-20200095,Disability Inclusive Development (DID) Programme - TO40 Kenya Covid-19 response,HI is part of the task order led by Light for the World for the needs of persons with disabilities in the Covid-19 crisis.,,2020,N/A,49307.41,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27401,GB-GOV-13-FUND--GCRF-AH_V006657_1,Designing Digital Sustainable Futures: Crafting through COVID-19 crisis,"The project develops an inclusive low cost sustainable digital ecosystem for craft and to theorise the valuation processes for craft in a digital environment, to address and respond to the impact of COVID-19 on the craft sector in Uzbekistan SDGs 17, 11 COVID-19",,2021,N/A,183168.77,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P27404,GB-GOV-13-FUND--GCRF-MR_V034952_1,Tracking Haulage in East Africa to support COVID-19 surveillance- THEA-C19,MRC GECO COVID award to develop and test digital contact tracing technology tailored to the haulage industry within Uganda COVID-19,,2020,N/A,617948.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +P27406,GB-GOV-1-301374,Covid-19 Response in Indonesia 'Äì Oxygen Therapeutics,To provide of c.42 units of ventilators to Indonesia. This will assist the Government of Indonesia in delivering its critical healthcare response to Covid-19. The equipment will be distributed to hospitals assessed as most in need by Indonesia'Äôs Ministry of Health with support from UNICEF.,,2021,N/A,1096950.58,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P27408,US-EIN-37-1552838-43,Kea Medicals - Launch new features to existing app - Free COVID-19 self-diagnosis,Launch a telemedicine service (the first in Benin) and built a COVID-19 self-diagnosis tool.,,2020,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P27409,GB-CHC-1082565-20200082,Disability Inclusive Development (DID) Programme - TO36 Nepal Covid-19 response,The task order activities are based on a rapid needs assessment undertaken in collaboration with local DPOs to identify the needs of persons with disabilities in the Covid-19 crisis.,,2020,N/A,223124.77,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27411,GB-GOV-13-FUND--GCRF-MR_V030825_1,The DOMINO Study: Measuring and mitigating the indirect effects of COVID-19 on TB and HIV care in Indonesia,MRC GECO COVID award to measure and mitigate the indirect effects of COVID-19 on TB and HIV care in Indonesia COVID-19,,2020,N/A,1016309.13,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Other,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27414,GB-GOV-13-FUND--GCRF-AH_V008307_1,Future Festivals South Africa: Possibilities for the Age of Covid-19,"Project investigates the impact of COVID-19 on festivals in South Africa, in partnership with the country'Äôs important arts festivals. The project builds a new knowledge base to enable SA'Äôs festivals to survive through developing networks. SDG 11,10 COVID-19",,2020,N/A,150708.92,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27415,GB-GOV-13-FUND--GCRF-MR_V03698X_1,The Impact of COVID-19 Control measures on NCD risk factors and Metabolic health: A comparison of 3 Caribbean countries,MRC GECO COVID award looking at the impact of COVID-19 controlmeasures on NCD risk factors and Metabolic health in Jamaica COVID-19,,2020,N/A,395512.1,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27417,GB-GOV-1-301253,COVID-19 Green Response and Recovery Support,"Tackling climate change, environmental degradation and biodiversity loss are priorities for UK foreign policy. Together they present some of the biggest threats to progress on sustainable development and poverty reduction with their impacts disproportionately affecting the poor and the vulnerable. In an environment of uncertainty arising from the COVID-19 pandemic, green and inclusive approaches offer an opportunity for sustainable recovery and growth. As post COVID-19 economic recovery packages are designed and rolled out, there is a strong opportunity to link them substantively to the planning and investment decision making undertaken in the 'ÄòNationally Determined Contribution'Äô (NDC) and National Adaptation Plan (NAP) processes. FCDO will provide an investment to deliver technical assistance for MDB recovery packages. The core objective is to support developing countries in their efforts to accelerate the transition to low-carbon, inclusive and resilient economies.",,2020,N/A,6383315.04,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts | Other secondary impacts,2020 +P27419,GB-GOV-1-301186,Solidarity Fund response to Covid-19 in South Africa,"The Solidarity Fund is a public benefit organisation with a mandate to support the national health response, contribute to humanitarian relief efforts and mobilise South Africans in the fight against COVID-19. The programme will benefit the most vulnerable communities",,2020,N/A,3469780.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27421,GB-GOV-13-GCRF-MR-C-GU-GamPC-2,Covid-19 Excess Mortality and Seroprevalence study for MRC Unit The Gambia at LSHTM,MRC GCRF Award conducting a Covid-19 Excess Mortality and Seroprevalence study for MRC Unit The Gambia at LSHTM COVID-19,,2021,N/A,407634.75,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2021 +P27422,GB-GOV-1-301180,Responding to Covid-19 in the Caribbean,"The objective of the Programme is to help contain the spread of the COVID-19 pandemic in the Caribbean and mitigate some of its worst impacts. While the immediate focus will be on the health response, support will also be provided for activities focused on mitigating the wider social, economic and security impacts, and protecting the most vulnerable.",,2020,N/A,6171569.64,Human Populations,Other,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2020 +P27423,GB-GOV-13-FUND--GCRF-MR_V030817_1,Development and pilot testing of an m-health intervention to reduce COVID-19 associated psychosocial distress among Nigerian healthcare workers,MRC GECO COVID award to develop and pilot test an m-health intervention to reduce COVID-19 associated psychosocial distress among Nigerian healthcare workers COVID-19,,2020,N/A,217088.69,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Economic impacts | Health workforce,2020 +P27424,GB-GOV-13-FUND--GCRF-MR_V028537_1,"Measuring unanticipated opportunity costs of South Africa's COVID-19 response for children, mothers, and people living with non-communicable diseases","MRC GECO COVID award to measure unanticipated opportunity costs of South Africa's COVID-19 response for children, mothers, and people living with non-communicable diseases COVID-19",,2020,N/A,881451.96,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27429,GB-GOV-1-301271,COVID-19 vaccine funding for the COVAX Advance Market Commitment (AMC),The UK is supporting early access to COVID-19 vaccines for the world'Äôs poorest countries through a commitment to the COVAX AMC (Advance Market Commitment) using the International Financing Facility for Immunisation (IFFIm). This contribution will support access to at least 1 billion vaccine doses during 2021 for 92 developing countries. This will contribute to ending the acute phase of the COVID-19 pandemic by reducing morbidity and mortality. Supporting access for the world poorest countries demonstrates UK commitment to vaccine multilateralism and supports the UK'Äôs international objectives of bringing the pandemic under control and supporting global economic recovery.,,2021,N/A,680642133.3,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P27431,GB-GOV-13-FUND--GCRF-MR_V036912_1,Indigenous peoples responding to Covid-19 in Brazil: social arrangements in a Global Health emergency,MRC GECO COVID award to identify indigenous responses and help to mobilise strategies to mitigatethe servere impact of the pandemic on indigenous people in Brazil. COVID-19,,2020,N/A,556639.99,Human Populations,Unspecified,Unspecified,Unspecified,Indigenous People,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27433,GB-GOV-13-FUND--GCRF-MR_V036890_1,Serological tools for COVID-19 control and vaccine roll-out in Southeast Asia,MRC GECO COVID award to evaluate new serological targets and establish assays that can be implemented to assist a surveillance system to monitor the progress of vaccination and SARS-CoV-2 elimination in the Thailand and Philippines community COVID-19,,2020,N/A,481502.26,Human Populations | Other,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2020 +P27436,GB-GOV-13-FUND--GCRF-MR_V028561_1,Promoting health and safety in traditional food markets to fight COVID-19 in Peru and Bolivia,MRC GECO COVD award on how to promote health and safety in traditional food markets to fight COVID-19 in peru and Bolivia COVID-19,,2020,N/A,966520.7,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27439,GB-GOV-13-FUND--GCRF-MR_V033433_1,The Impact of the COVID-19 Pandemic on People with Severe Mental Illness and on Mental Health Service Provision in South Asia (IMPASS),MRC GECO COVID award to look at the impact of the COVID-19 Pandemic on People with Severe Mental illness and on mental health service provision in South Asia COVID-19,,2021,N/A,64277.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P27440,GB-GOV-13-FUND--GCRF-MR_V036939_1,REBRACOVID' - multicentre cohort study of the natural history and immunology of COVID-19 in Brazil,"MRC GECO COVID award to better understand susceptibility and mechanisms underlying this disease, drawing on specific insights from the serious situation in Brazil to impact local management of the response. COVID-19",,2020,N/A,1278943.25,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Immunity | Disease susceptibility",2020 +P27442,GB-GOV-13-FUND--GCRF-MR_V035924_1,Healthcare and Socio-economic Impacts of COVID-19 on Patients with Diabetes in Tanzania and Kenya,MRC GECO COVID award to explore the experiences of people within Diabetes in Tanzania abd Keya type 2 diabetes (T2D) and healthcare providers on managing T2D during COVID-19.,,2021,N/A,109645.89,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P27451,NO-BRC-977538319-SOFM2032,Protecting vulnerable communities in Somalia from the spread and impact of the COVID-19 virus through the BRCiS consortium (Closed),"Following the emergence and declaration of COVID-19 pandemic, BRCIS re-programmed around 5,5M GBP worth of activities for all BRCiS locations to scale up sensitization, health and nutrition outreach, WASH activities and livelihoods through the use of cash. The activities were anchored within a wider BRCiS collective COVID-19 preparedness and response plan.",,2020,N/A,149383.48,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,,2020 +P27452,GB-GOV-13-FUND--GCRF-MR_V033441_1,"COVID-19 Neurological Disease: a Global Meta-Analysis and Prospective Case Control Study in Brazil, India and Malawi.","MRC GECO COVID-19 Neurological Disease award: a Global Meta-Analysis and Prospective Case Control Study in Brazil, India and Malawi COVID-19",,2020,N/A,1116273.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Epidemiological studies,,2020 +P27453,GB-CHC-290767-ALERTCV19103_S12426_A,Helping schools in Manica and Sofala to prevent the spread of COVID-19,"In response to the initial spread of COVID-19, the Government of Mozambique closed both public and private schools on the 23rd of March 2020. This decision affected a total of 8.5 million children. Schools are currently scheduled to open in February 2021. While the initial disruption to children'Äôs education has been significant, there is the possibility for further disruption if schools are unable to meet the COVID-19 safety standards prior to opening. If schools do not have adequate COVID-19 mitigation procedures and equipment in place they will be prevented from opening, thus potentially further disrupting children's education. While the COVID-19 pandemic has presented difficulties and unique challenges to the entire population of Mozambique, communities that were still recovering from previous natural disasters have been especially affected by COVID-19. In particular, a number of communities in Sofala and Manica provinces were severely impacted by Cyclone Idai in 2019, a devastating cyclone that wreaked massive destruction and resulted in the sustained disruption for the region'Äôs livelihoods and educational infrastructure (we responded to this at the time). Over a year after Cyclone Idai and at the outset of the COVID-19 pandemic, Sofala and Manica were still home to 20 of the most neglected resettlement sites and surrounding areas. In these areas, families were still struggling to rebuild, recover their livelihoods, and renew their children'Äôs education. Inevitably, the COVID-19 crisis made an already difficult situation for displaced communities in Sofala and Manica even worse. The tertiary impacts of the pandemic, specifically the shutting down of schools which further disrupted children'Äôs education and families'Äô livelihood opportunities, have been devastating and require immediate steps to be taken to prevent the situations from worsening. It is undoubtedly true that these secondary impacts of the COVID-19 crisis are felt throughout Mozambique, however, the impacts have been magnified in Sofala and Manica provinces where the communities were already struggling to recover economically and educationally in the aftermath of Cyclone Idai. Project: This proposed project and response will address two clear issues in Sofala and Manica provinces: the disruption of children'Äôs education and the disruption of livelihoods for vulnerable families. Following assessments of needs and markets, we are proposing to target 1,600 households (8,000 individuals) to benefit by providing schools with the necessary items to properly and regularly sanitise classrooms, carry out sensitisation and awareness campaigns on COVID-19 prevention measures that involve for students and their families, installing water tanks and handwashing apparatuses at schools, and providing agricultural livelihood inputs for particularly in-need families. The project will target beneficiaries in Sofala and Manica provinces whose education and livelihoods were severely disrupted by Cyclone Idai and then further disrupted by the arrival of the COVID-19, compounding their already difficult circumstances. Special attention will be placed on ensuring that girls especially will be returning to schools after this disruption, as we know from previous epidemics that enrolment rates for girls dropped as increased rates of poverty, household responsibilities, child labour, early marriage and teenage pregnancy prevented many girls from returning to school. The COVID-19 safety packs will contain the following for each school administration: - 100 boxes of soap x 12 - 5 buckets with taps 100L each - 4 sprayers for each school to disinfect the classroom -5 Two thermometers Regarding livelihood support, this project will target the most vulnerable and in-need families of school-age children to provide with agricultural livelihood inputs, which predominantly includes women headed families. These inputs will allow families in need to begin to provide for their children a source of sustenance and potential income. The agricultural livelihood inputs will include mixed seeds (maize, beans, and vegetables) and hoes. Lastly, due to the heightened risk of Gender Based Violence (GBV) and protection issues in the communities, we will involve the training of community activists on GBV issues, including a referral system to protect, defend and report cases in the target areas. In addition, at all distributions and activities, we will be distributing leaflets and conducting mass sensitisation campaigns highlight the risks of GBV, how to protect oneself, and how to report/respond to incidents.",,2020,N/A,212763.53,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Gender,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P27454,KE-RCO-CPR-2009-5689-3583-COVID19,Safe Trade Kenya Country Programme -Tech Interventions (COVID-19),"Safe Trade Cluster 2 technology works will focus on three key broad intervention areas: 1. Regional Electronic Cargo and Driver Tracking System (RECDTS) A digital-based solution that provides a trusted framework for sharing the mutually recognised EAC COVID-19 Test Certificates among Ministries of Health in the EAC, to facilitate movement of truck drivers across the region through elimination of multiple testing at entry points in the times of COVID-19. Support areas include; a. System development 'Äì including development of drivers, health, and enforcement officers mobile applications; geo-fencing of designated stop/rest areas along the major trade corridors in the EAC b. System integrations/interfaces to National Laboratory Systems. c. System Infrastructure and operational support framework for the anchor platform (RECTS) - hosting support. d. Change management activities 'Äì sensitization/training of users (truck drivers, truck companies, health, and enforcement officers) 2. Paperless border transactions Enhancement of the SCT centralised platform to include automation of transit documents. This will limit the use of paper - a potential conduit of virus transmission, as well as limit human interaction in the times of COVID-19. 3. Automatic identification and verification technologies (subject to availability of funds) These will automate and further enhance clearance and release processes at border crossings, utilising technology to limit human interaction. These technologies will include; a. Smart gates. b. Optical Character Recognition (OCR). c. Facial recognition. d. Automatic number plate reader.",,2020,N/A,1476262.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P27459,NO-BRC-977538319-SOFM2024,Protecting vulnerable communities in Somalia from the spread and impact of the Covid-19 virus through the BRCiS consortium (Closed),Protecting vulnerable communities in Somalia from the spread and impact of the Covid-19 virus,,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,,2020 +P27461,GB-GOV-13-FUND--GCRF-MR_V029363_1,"The impact of COVID-19 on primary health care service provision and utilisation in Tanzania, Sierra Leone and the Democratic Republic of Congo","MRC GECO COVID award to look at whether the attendance of routine services, like antenatal care, immunisations and HIV treatment services, have been affected by the COVID-19 pandemic in 3 countries in East, West and Central Africa. COVID-19",,2020,N/A,1103611.34,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27462,GB-GOV-13-FUND--GCRF-AH_V006428_1,"A Study of COVID-19 Adaptation Strategies for Residents of Multi-tenanted Housing in Lagos, Nigeria","The project provides research support for the prevention of community spread of COVID-19 amongst residents of multi-tenanted housing in Lagos, through historical analysis, policy responses and examine the role of audio arts. SDG 11, 3 COVID-19",,2020,N/A,180505.97,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Infection prevention and control | Policies for public health, disease control & community resilience",Community engagement,2020 +P27464,GB-GOV-13-FUND--GCRF-AH_V007963_1,"Covid-19 in Kenya: Global Health, Human Rights and the State in a Time of Pandemic","Project documents and evaluates the legal policy responses to the COVID-19 pandemic in Kenya, giving voice to vulnerable and impoverished communities effected by the measures, and to policy makers concerned with their implementation. SDG 3 COVID-19",,2020,N/A,178161.37,Human Populations | Other,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts,2020 +P27467,US-EIN-37-1552838-82,Agrocentra - Providing smallholder farmers with trusted information on COVID-19,"Create a digital advisory service, known as Sentinel, which transmits health and safety information on COVID-19 to smallholder farmers through IVR channels. Providing this information to smallholder farmers is vital as they still rely heavily on non-mechanised farming, requiring them to operate in close proximity to one another, which can enable the virus to spread more easily.",,2020,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Farmers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P27471,GB-GOV-13-FUND--GCRF-AH_V008684_1,Using the arts to mitigate the impact of Covid-19 among India's indigenous and nomadic communities,"Understand and mitigate the effects of the Covid-19 pandemic on India's mobile Scheduled Tribes and DeNotified Tribal groups, using the arts to advance indigenous rights, community building and resilience in the context of the pandemic. SDGs 11, 10, 3 COVID-19",,2021,N/A,149230.25,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P27478,GB-GOV-1-301205,Supporting COVID Response in the Greater Mekong Sub-region through Health Systems Strengthening,"The programme will provide support on strengthening heath systems in the Greater Mekong Subregion (GMS) to prevent, detect and control the threat of COVID-19. The programme will work in Cambodia, Laos, Myanmar and Vietnam and will also involve Thailand in regional initiatives.",,2020,N/A,6403303.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P27479,US-EIN-37-1552838-99,"Loowatt - support the servicing and maintenance of waterless, container-based household toilets in the context of the COVID-19 pandemic","Support the servicing and maintenance of waterless, container-based household toilets in the context of the COVID-19 pandemic",,2020,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures | Infection prevention and control",Indirect health impacts,2020 +P27497,GB-GOV-13-FUND--GCRF-MR_V035592_1,Ensuring access to health care and medicines during COVID-19: critical challenges and feasible policy options for the medicines retail sector,MRC GECO COVID award to understand and mitigate the vulnerability of supply and access to medicines within the Uganda health system COVID-19,,2020,N/A,425777.49,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Health Systems Research,"Medicines, vaccines & other technologies",2020 +P27499,GB-CHC-228248-P000204,"Data Driven Response to the Covid-19, Climate Change and Food Security Nexus","Provide DFID and other stakeholders with modeling that better anticipates possible trajectories that vulnerable countries will take with COVID-19, with a particular emphasis on the unprecedented ways in which food insecurity may increase due to factors not typically considered by food security experts.",,2020,N/A,199384.07,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P27501,GB-CHC-1082565-20200079,"Supporting Preparedness, Mitigation and Response to the COVID-19 pandemic in the Central African Republic (SPMR 'Äì CAR)","Supporting the most vulnerable to benefit from enhanced protection against the COVID-19 pandemic through support to the inclusive preparedness, mitigation and response capacities of national and local actors.",,2020,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27513,NO-BRC-977538319-YEFM2025,"Supporting preparedness, mitigation and response to the primary and secondary impacts of COVID-19 on IDP and vulnerable populations in Yemen (Closed)","Given the context of COVID-19, combined with the already dire humanitarian needs in Yemen, our approach aims to prevent, mitigate and respond to COVID-19: in the immediate/short-term by providing life-saving assistance through targeted and coordinated activities in WASH, protection, and cash to IDP and vulnerable populations. The programme will provide an integrated, package across two governorates; Hodeidah and Taizz.",,2020,N/A,928938.31,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27515,GB-CHC-1158838-DFI001R-ETOO,Ethiopia Emergency Covid-19 Response Fund,"The Freedom Fund has established a Covid-19 Emergency Response Fund (ERF) to offer immediate humanitarian assistance through small-scale funding to some 100 frontline partners working with vulnerable communities in India, Nepal, Myanmar, Ethiopia, Thailand and Brazil (part of its established hotspot programme).",,2020,N/A,103826.24,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts | Other secondary impacts,2020 +P27516,GB-CHC-1158838-DFI001R-INRA,Rajasthan Emergency Covid-19 Response Fund,"The Freedom Fund has established a Covid-19 Emergency Response Fund (ERF) to offer immediate humanitarian assistance through small-scale funding to some 100 frontline partners working with vulnerable communities in India, Nepal, Myanmar, Ethiopia, Thailand and Brazil (part of its established hotspot programme).",,2020,N/A,6228.17,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27527,XM-DAC-47066-MP.0472,"Prepare, Prevent, Protect: Mitigating the Destabilizing Socio-Economic Impact of COVID-19 on Most Vulnerable and Conflict-Prone Communities in Mindanao","With the Philippines anticipating cycles of high transmission rates of COVID-19 and the differential implementation of community quarantine across the country until the pandemic subsides, marginalized social groups and internally displaced persons are likely to be disproportionately impacted by restrictive interventions. In response to these challenges, IOM Philippines will adopt its 'ÄúPrepare, Prevent, Protect'Äù approach to mitigate the destabilizing socio-economic impact of COVID-19 on most vulnerable and conflict-prone communities in Mindanao.",,2020,N/A,1251147.38,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P27528,GB-CHC-1128267-8-STARTColombia2020,"START: Provision of PPE, hygiene items, awareness raising, cash, food security in response to COVID-19 in Colombia","Rapid humanitarian response to impacts of the COVID-19 crisis on Older Persons, People with Disabilities, and Venezuelan Caminantes, returnees and homeless in La Guajira, North Santander and Santander, Colombia",,2020,N/A,236456.13,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27534,GB-GOV-13-FUND--GCRF-AH_V008005_1,Phone panel survey to evaluate how COVID-19 and related mitigation interventions are impacting women and children in Sierra Leone,"Project explores how COVID-19 and related mitigation measures are impacting women and children through effects on livelihoods and incomes, gender-based violence, access to CV-19 education messages and exposure to misinformation. SDG 3, 5, 10 COVID-19",,2020,N/A,173382.82,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Gender,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P27537,GB-GOV-13-GCRF-AH-C-UG-UN2020AH-V013505-1,The impacts of COVID-19 on Persons with Disabilities in Ukraine (with a particular focus on internally displaced Persons with Disabilities),"Qualitative, co-designed research methods investigating the impact of COVID-19 on the intersecting inequalities of (dis)location, disability, gender and age. Benefits internally displaced persons with disabilities in Ukraine. SDGs: 5, 10 COVID-19",,2021,N/A,125159.33,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Gender,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P27538,GB-GOV-13-FUND--GCRF-AH_V006525_1,Supporting Just Response and Recovery to COVID-19 in Informal Urban Settlements: Perspectives from Youth Groups in Sub-Saharan Africa,"Project looks at the ethical and justice issues arising from the impact of COVID-19 and related control measures on vulnerable groups in informal urban settlements in sub-Saharan Africa, and disseminate information within informal settlements SDG 3, 10, 11 COVID-19",,2020,N/A,174955.87,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Social impacts,2020 +P27539,GB-GOV-13-GCRF-AH-C-UG-UN2020AH-V013548-1,The impact of COVID-19 on people living with psychosocial disabilities in Ghana and Indonesia and priorities for inclusive recovery,"Explores the impact of COVID-19 on people with mental health conditions in Ghana and Indonesia to better inform guidelines to include them in recovery plans. Benefits people with psychosocial disabilities in Ghana and Indonesia. SDGs: 3, 8, 10 COVID-19",,2021,N/A,128969.32,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P27549,GB-GOV-13-GCRF-AH-C-UG-UN2020AH-V013459-1,Participatory Action Research with Disabled Adolescents in Nepal (PARDAN) to develop methods and materials to understand their experience of COVID-19,"Participatory Action Research with Disabled Adolescents in Nepal develops methods and tools to increase the participation of children and young people with disabilities in research about their experiences of the COVID pandemic in Nepal. SDGs: 4, 10 COVID-19",,2021,N/A,118413.8,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P27550,GB-GOV-13-GCRF-AH-C-UG-UN2020AH-V013432-1,"Implementing participatory-action research to explore the impact of COVID on war-affected disabled populations, including ex-child soldiers, in Uganda","Disability-inclusive research assessing the impact of COVID-19 on war-affected disabled populations. Benefits people in Uganda with war-related disabilities by informing disability-inclusive pandemic recovery strategies. SDGs: 1, 3, 5, 8, 10, 16, 17 COVID-19",,2021,N/A,112588.66,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P27551,GB-CHC-1128267-8-OPT100,START OPT 2020: Awareness and protection of older women and men against Covid-19 in the Gaza strip,"COVID-19 emergency response for vulnerable older women and men in Gaza. Through its international and national partners, HelpAge International UK aimed to protect older men and women through hygiene kits, PPE, and awareness raising.",,2020,N/A,55430.85,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Women,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27552,GB-CHC-1158838-DFI001R-INSO,Southern India Emergency Covid-19 Response Fund,"The Freedom Fund has established a Covid-19 Emergency Response Fund (ERF) to offer immediate humanitarian assistance through small-scale funding to some 100 frontline partners working with vulnerable communities in India, Nepal, Myanmar, Ethiopia, Thailand and Brazil (part of its established hotspot programme).",,2020,N/A,132773.2,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27553,GB-CHC-1158838-DFI001R-INNO,Northern India Emergency Covid-19 Response Fund,"The Freedom Fund has established a Covid-19 Emergency Response Fund (ERF) to offer immediate humanitarian assistance through small-scale funding to some 100 frontline partners working with vulnerable communities in India, Nepal, Myanmar, Ethiopia, Thailand and Brazil (part of its established hotspot programme).",,2020,N/A,64099.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27560,GB-CHC-1047501-RRF-Covid19-Response-Yemen,"Supporting preparedness, mitigation and response to the primary and secondary impacts of COVID-19 on IDP and vulnerable populations in Yemen","Given the context of COVID-19, combined with the already dire humanitarian needs in Yemen, our approach aims to prevent, mitigate and respond to COVID-19 in the immediate/short-term, by providing life-saving assistance through targeted and coordinated activities in health, nutrition, WASH, protection, and cash to IDP and vulnerable populations. The programme will provide an integrated, multi-partner package across three governorates (Abyan, Lahj, and Shabwah), as well as within Azurrah district in Hodeidah, and limited activities targeting highly vulnerable IDP populations in Taizz.",,2020,N/A,3730790.83,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants | Vulnerable populations unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",,2020 +P27569,GB-CHC-1062638-CVA20,COVID-19 Appeal,"Here in the UK we'Äôve all had to make sacrifices to protect each other and save lives during the coronavirus pandemic, and witnessed the incredible dedication of our amazing NHS staff. But as we struggle with the virus at home, people around the world need our help 'Äì families who have fled violence, conflict and hunger in countries where there is no NHS if they fall ill. Many are now living in crowded refugee and displacement camps with little access to medical care, clean water or enough food, making them extremely vulnerable to coronavirus. In these places, the virus is likely to be even more deadly than it has been here. Imagine having to leave everything behind to keep your family safe, only to face a deadly new threat: Covid-19. This is the reality for people living in tents and makeshift shelters without running water or soap in places like Syria, Yemen and Somalia. But, as we have seen in the UK, simple measures can make a huge difference. If we act now to protect millions of vulnerable refugees and displaced people, many lives can be saved. We need your help to: provide families with clean water, soap and information on keeping themselves safe provide frontline medical and aid workers with equipment and supplies to care for the vulnerable and sick ensure families get enough food to prevent malnutrition, particularly amongst children People who have already suffered so much need your help now more than ever to face this new threat. Please give whatever you can at this challenging time for us all.",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P27571,GB-GOV-13-GCRF-AH-C-UG-UN2020AH-V013688-1,"Creating recovery: a case-study of how autistic people, families, health professionals & artists in Peru can build inclusive learning through COVID-19","Interrogates how innovative theatre-based methodologies can be adapted to enable resilience to and inclusive recovery from Covid-19 by autistic individuals. Benefits autistic people, families, health professionals and artists in Peru, as well as Argentina, Brazil and Colombia. SDGs: 3, 4, 10 COVID-19",,2021,N/A,125885.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P27579,GB-COH-RC000749-DWIN-MFI22-004,Understanding immediate impacts of Covid-19 on coastal communities in Mozambique,"The project aims to fill critical gaps in our understanding of the socioeconomic and environmental impacts of Covid-19 on coastal communities in northern Mozambique. The data will inform development of coping mechanisms for communities, increase resilience to shocks and support recommendations for scalable community-based solutions. We will focus on enhancing knowledge around key pillars including governance and co-management of marine resources, community behaviour and biological impact on fisheries, to inform the knowledge base and strategies for long term community resilience.",,2021,N/A,73668.05,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2021 +P27584,GB-GOV-13-FUND--GCRF-AH_V007998_1,Belief in the time of Covid-19: Understanding the making of meaning and trust to maximise public health responsiveness of faith communities in DRC,"Project seeks to understand faith-health beliefs during COVID-19 in order to contribute to effective public health communication and action through faith communities in the regions of Ituri and Nord-Kivu, in the North East DRC. SDGs 10, 3 COVID-19",,2020,N/A,119987.94,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P27587,GB-GOV-13-GCRF-MR-C-GU-GamPC-19061,"MRC Gambia Unit fund to set up test facilities, increase clinical service capacity, engaging with the community in The Gambia to test for COVID-19","MRC GCRF Award -Testing for COVID-19 on behalf of the Gambia Government, set up testing facilities in our labs in Basse and Keneba, double Clinical Services Capacity in Fajara and Keneba, Provision of PPE, Community Sensitization and community engagement. COVID-19",,2020,N/A,742787.74,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience | Health Systems Research",Diagnostics | Community engagement | Health service delivery,2020 +P27591,GB-GOV-1-301364,The sharing of 100 million doses of the Covid-19 vaccines with countries in need,At the G7 Summit on 11 June 2021 the Prime Minister announced the United Kingdom (UK) will donate 100 million surplus Covid-19 vaccines to the world within a year; 80 million will go through COVAX and 20 million will be donated bilaterally. 5 million of these will be donated by the end of September 2021 and 30 million by the end of 2021.,,2021,N/A,5054268.08,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Vaccine logistics and supply chains and distribution strategies,2021 +P27607,GB-GOV-1-301301,Sharing lessons learned from Brazil'Äôs Social Protection response to COVID-19,"A one-year programme funding the World Bank to analyse, document and disseminate Brazil'Äôs successful experience with the emergency benefit to protect vulnerable populations from the economic impacts of the COVID-19 pandemic. Although Brazil has had difficulties controlling the spread of the virus, its emergency cash transfer programme (Auxilio Emergencial, AE) has been one of the largest and most rapidly deployed social protection programmes in the world, helping 67 million informal workers who would otherwise have struggled badly. Sharing these learnings through this FCDO project meets a demand from poorer countries who have been seeking advice on how to improve their social protection policies at speed and during a crisis.",,2021,N/A,71262.85,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P27611,GB-GOV-13-FUND--GCRF-AH_V007947_1,Whose crisis?: The global COVID-19 crisis from the perspective of communities in Africa,"Project amplifies the voices of under-represented and under-served communities in Africa to contribute to the understanding of Global Health in a pandemic context, by documenting and communicating plural and diverse lived experiences. This activity benefits Uganda;Malawi;Eswatini;Nigeria;Botswana SDG3 ,10 COVID-19",,2020,N/A,183407.51,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2020 +P27616,US-EIN-27-1661997-Kenya-COVID19-FCDO-2020,Provision of Cash Transfers for Urban Poor People Living in Informal Settlements in Response to COVID-19,"The project provides emergency cash relief to vulnerable people in urban and peri-urban areas of Kenya suffering severe hardship as a result of COVID-19. This is based on work GiveDirectly launched early in 2020 (an inclusive, remote, emergency cash assistance response program where recipients were targeted through partnerships with trusted CBOs). The project provides each recipient with 3,000 KES (~¬£22) per month for four months. This transfer size was designed to enable recipients to avoid the worst economic consequences of COVID-19, while enabling the program to reach as many vulnerable households as possible.",,2020,N/A,6448640.75,Human Populations,Black,Unspecified,Urban Population/Setting | Other,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P27626,GB-CHC-1128267-8-START_Syria_2020,START Syria 2020: Strengthening COVID-19 emergency response for vulnerable older women and men in Idlib in NW Syria,"Strengthening COVID-19 emergency response for vulnerable older women and men in Idlib in NW Syria. Through its international and national partners, HelpAge International UK aimed to reach one of the most vulnerable groups in the community who are usually a hidden segment in any society, especially in humanitarian contexts. Our main target group was be older men and women including those with disabilities in Idlib governorate, in urban, camps and Informal Tented Settlements (ITS) settings.",,2020,N/A,101510.28,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Disabled persons | Women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27628,US-EIN-37-1552838-102,"Uduma - In the context of the COVID-19 pandemic, install 333 foot-operated handwashing facilities near its water points and to supply over 18,000 bars of soap to communities. Launch a 'Äòclean hands'Äô campaign, which aimed to increase handwashing in Burkina Faso.","In the context of the COVID-19 pandemic, install 333 foot-operated handwashing facilities near its water points and to supply over 18,000 bars of soap to communities. Launch a 'Äòclean hands'Äô campaign, which aimed to increase handwashing in Burkina Faso.",,2020,N/A,,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27629,GB-COH-NI21482-TNIUKAM23ZIM,Improved food security and coping strategies for vulnerable women and men affected by drought and long-term impacts of Covid-19 in Southern Zimbabwe,"Support families in Zimbabwe who face chronic food insercurity caused by drought and climate change, now further exacerbated by the impact of Covid-19. Women, as the primary producers of food, need to be supported and protected in the faceof harmful and violent cultural gender norms.",,2023,N/A,2453482.11,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women | Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P27630,XM-DAC-47066-IB.0183,Immediate Response to COVID-19 Pandemic for Effective Border Management in Nigeria,"IOM in anticipation of the opening of the airspaces, proposes to equip the selected points of entries (PoEs) with necessary personal protective equipment (PPE) and other tools necessary for adequate border management through a public health emergency lens. In line with the National COVID-19 Multi-Sectorial Pandemic Response Plan's pillar on PoEs, IOM seeks to strengthen and increase surveillance at PoEs, including capacity building of the relevant PoE entities. The Nigeria Centre for Disease Control has in this Response Plan detailed the type of PPEs and materials that the Port Health Services (PHS) and the Nigeria Immigration Service (NIS) would need to adequately protect themselves while in the line of duty as front-line workers. Central to infection, prevention and control (IPC) is the strengthening of weak water sanitation and hygiene (WASH) systems at PoEs, in some instances, these are non-existent and will need to be established. WASH systems play an important role in IPC, and it is important to ensure that PoEs are decked out with the necessary infrastructure to ensure that IPC is effectively conducted. To complement all the aforementioned interventions, IOM will seek to provide the PHS with computers to enable them to establish electronic system for adequate border management.",,2020,N/A,771168.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P27632,US-EIN-37-1552838-47,Sehat Kahani - Integration of an AI chat bot that will help users conduct self-diagnosis,"Integration of an AI chat bot that will help users conduct a quick self-diagnosis for COVID-19 Online audio & video consultations for helping potential COVID-19 patients diagnose and manage symptoms. Create a real- time dashboard to track COVID-19 cases in the country, identify infection hotspots and treatment facilities",,2020,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P27633,GB-CHC-292506-GB785,START Fund Timor Leste COVID19,Early anticipation action to mitigate risk of COVID-19 transmission and clusters in high risk areas on theTimor-Leste/ Indonesia land border. This project will respond to gaps and unmet needs for preparation against COVID-19,,2020,N/A,44508.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +P27634,CH-FDJP-110.162.567-FIND2021,Ensure equitable access to reliable diagnosis around the world,"Despite the ongoing challenges of the COVID-19 pandemic, FIND capitalized on its recently launched strategy and achieved its 2021 goals, delivering an average of 81% of programmatic performance objectives (versus 80% target). Outside COVID, four products in FIND'Äôs product development portfolio received regulatory clearance; evidence was generated to support six World Health Organization (WHO) recommendations and policy documents; and 36 clinical studies were conducted, 28 of which relied on newly developed approaches to remote work and remote training. Notably, in 2021, FIND was especially focused on its role in supporting global access to COVID-19 tests and genomic sequencing, through its role in the Access to COVID-19 Tools Accelerator Diagnostics Pillar (ACT-A Dx). In part, this meant engaging substantially with multiple global agencies, and absorbing a large injection of COVID-19 work into ongoing work across FIND'Äôs disease portfolio, including in pandemics threats.",,2021,N/A,72491319.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Health Systems Research,Health service delivery,2021 +P27635,GB-GOV-13-GCRF-InCCARE,Royal Academy of Engineering Innovation & Commercialisation - Africa Prize CARE,"Project CARE aims to support African Engineering entrepreneurs to make and supply PPE which is effectively used in hospitals and clinics in sub-Saharan Africa, as well as to respond to other COVID-19 related challenges in their communities. COVID-19",,2020,N/A,735364.74,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P27636,GB-CHC-292506-GB791,DFID-RRF Sahel COVID19,"Sahel Covid-19 Response in Chad, Niger and Mali",,2020,N/A,3730615.48,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,,,2020 +P27637,GB-CHC-228248-F0300200,Stopping Abuse and Female Exploitation (SAFE) Programme Zimbabwe,"This mixed methods research into poverty dynamics in the context of Covid-19 in Zimbabwe has a strong focus on vulnerability and resilience and employs Covid appropriate research methods and processes. It is hoped that the research products delivered by this project will contribute to evidence-based decision-making, and pro-poor programming and policy development.",,2020,N/A,199467.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P27639,GB-GOV-13-GCRF-MR-C-GU-UgPC-20011,Community surveillance for SARS-CoV-2 and COVID_19 in the general and in high risk populations in Uganda and assessment of the wider impact of infection and of pandemic mitigation,MRC GCRF COVID-19 conducting community surveillance for SARS_CoV_2 and COVID_19 in general and high risk populations n Uganda COVID-19,,2020,N/A,712582.28,Human Populations,Black,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping,2020 +P27640,GB-GOV-13-FUND--GCRF-MR_V030884_1,"African critical care registry network for pandemic surveillance, clinical management and research.","MRC GECO COVID award looking at the African critical care registry network for pandemic surveillance, clinical management and research. Our group of LMIC based co-investigators and project partners from established critical care and pandemic networks aims to address the knowledge gaps that exist regarding the natural history and clinical course of COVID-19 related critical illness in seven African countries - Ethiopia, Kenya, Namibia, Sierra Leone, South Sudan, Tanzania and Uganda. COVID-19",,2020,N/A,1435667.71,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +P27642,GB-GOV-13-FUND--GCRF-MR_V035444_1,Implementing genomic surveillance to support SARS-CoV-2 control and mitigation strategies in the Philippines,"MRC GECO COVID award to build genomic surveillance and response capacity in the Philippines, where it can inform infection control at local and regional scales COVID-19",,2020,N/A,796408.28,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2020 +P27643,GB-GOV-13-FUND--GCRF-MR_V028782_1,"To investigate the spectrum, determinants and long-term outcome of SARS-CoV-2 in African children, immune responses and protective role of prior sHCoV","MRC GECO COVID award to investigate the spectrum, determinants and long-term outcome of SARS-CoV-2 in African children, immune responses and protective role of prior sHCoV COVID-19",,2020,N/A,1038134.71,Human Populations,Black,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Post acute and long term health consequences",2020 +P27644,GB-COH-07157505-P000226,Rapid Response Service for Covid-19,"The objective of the Rapid Response Service is to draw from a pool of global, regional and local experts to provide short-term, high quality, data driven, impact-oriented and programmatically relevant research and evidence support. The Supplier will establish a Service that will provide rapid reviews and evidence syntheses based on the most recent data and literature 'Äì related to impact of C19 on poverty, vulnerability, the overall economy and across key sectors of the economy.",,2020,N/A,157589.32,Unspecified,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,Data Management and Data Sharing,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2020 +P27648,GB-GOV-13-FUND--GCRF-MR_V02860X_1,"SARS-CoV-2 infection, transmission dynamics and household impact in Malawi (SCATHIM)","MRC GECO COVID award to determine the transmission dynamics, determinants and socio-economic impact of SARS-CoV-2 infection in households located in urban mediumdensity, urban high-density and rural-high density locations in Malawi, Africa COVID-19",,2020,N/A,828566.62,Human Populations,Black,Unspecified,Rural Population/Setting | Suburban Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Social impacts | Economic impacts,2020 +P27650,GB-CHC-292506-GB799,DFID NERF Nepal (COVID19),The project aims to reach the most vulnerable to mitigate the secondary impacts of Covid and maintain resilience into monsoon season. The response will target 4 priority sectors,,2020,N/A,433484.46,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",,2020 +P27651,GB-COH-1364201-SLE100201,Hygiene and Behaviour Change Coalition,"Plan'Äôs goal is to contribute to the prevention and mitigation of further spread of COVID-19, and to alleviate human suffering of the most affected, especially among girls and women.",,2020,N/A,527012.83,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,,2020 +P27653,US-EIN-37-1552838-88,Drinkwell - Restart 50 ATM Booth Operations for the provision of safe water for low-income communities in Dhaka.,Reopen water ATMs in Dhaka after the enforced closures due to COVID-19 pandemic. This includes the re-hiring of caretakers it had previously furloughed to operate and manage the water ATMs.,,2020,N/A,,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2020 +P27654,GB-CHC-292506-GB793,START Fund Togo Conflict 2020,"This project is designed to provide immediate assistance to the displaced population and protect the affected communities from the spread of COVID-19. The project will: support 1,500 households (7,500 individuals) with a multi-sector response.",,2020,N/A,223130.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P27655,GB-CHC-292506-GB786,START Fund Alert 418 Tonga,"This intervention will integrate COVID-19 risk communications and community engagement (RCCE) with support of Town Officers and use of mass media, aligned with MoH and NEMO messaging; and will support household livelihoods to mitigate TC Harold",,2020,N/A,119362.55,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2020 +P27657,GB-CHC-292506-GB787,START Fund Laos COVID19,The project will utilize a range of mass media approaches to reach under served ethnic minority populations in target provinces with information and education in ethnic dialects and Lao language on COVID-19 so that they can better protect themselve,,2020,N/A,231025.07,Human Populations,Asian,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Communication,2020 +P27673,GB-GOV-1-301198,UK Jamaica Covid-19 Strategic Border Health Security Project,To support national and regional efforts to develop and implement strategies to re-open and maintain borders to enable safe passenger movement in the Caribbean Region.,,2020,N/A,407953.89,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +P27674,GB-GOV-1-301197,Coronavirus Relief for Indonesian Sustainable Peatland (CRISP),To provide a humanitarian response by supporting Government led response in tackling the COVID-19 outbreak in Indonesia. CRISP prevent uncontrolled fires in peatland areas and provide support to peatland communities affected by the economic and health impacts of the coronavirus pandemic.,,2020,N/A,1275814.69,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +P27675,AT-UID-U74408937-H2H_2020_BF2_GTS_expense,Strengthening accountability to affected populations through independent perception monitoring in Burkina Faso,Affected people'Äôs perceptions of humanitarian ongoing response of COVID-19,,2020,N/A,92757.69,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"Foreign, Commonwealth & Development Office (FCDO)",United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P27721,211746,COVID-19: Social policies put to the test by the pandemic,"In many ways, the COVID-19 pandemic has turned our lives upside down, testing social cohesion. Many social measures had to be reinvented and redeployed, particularly for those hardest hit by the crisis. What can we learn from this unprecedented period? What trends are emerging in the medium and long term, particularly for the most vulnerable groups? What will remain of the individual and collective initiatives that have emerged and what lessons can we draw from them to think about the social policies of tomorrow? To answer these questions, this work brings together works highlighting the extent of the social impact of the pandemic, as well as the responses provided to it. Paying particular attention to the dialogue between research and social policies, this book also includes interviews conducted with those responsible for social and health action at the federal, cantonal and municipal levels, as well as with research teams. The objective is to help stimulate this dialogue by highlighting its importance and challenges in managing the pandemic. The result of a collaboration between the academic world and the sphere of public policies, this work is aimed both at teachers, researchers and students, as well as at professionals and those responsible for social action and sanitary.",,2022,Haute école de travail social et de la santé HES-SO,16614.67,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Policy research and interventions | Social impacts,2022 +P27722,210115,Fit for Crisis? Social Policy in Times of COVID-19: a Longitudinal Mixed-Method Approach,"The COVID-19 pandemic has triggered unprecedented changes in the Swiss labour market, which are expected to have significant effects on the Swiss welfare system. We aim to explore the capacity of social policies to support vulnerable groups in times of crisis and prevent the deepening of inequalities. It is therefore crucial to understand to what extent social policies (including ad hoc programmes adopted since March 2020) have been able to buffer the socioeconomic effects of the pandemic over the long run. To do so, this project relies on a longitudinal mixed-methods approach that will be carried out by an interdisciplinary research team (including sociology, economics, social policy analysis and competencies in mixed-methods. Our ambition is to support evidence-based decisions by identifying (1) which target groups are particularly exposed to the risk of long-term unemployment and social assistance; and (2) what best practices could be promoted in order to improve the resilience of social policies in the context of future crises. Based on a close collaboration with federal and local administrations and relevant stakeholder in the field of social policy, the project pursues the following three core objectives:1. Document social policies at the local level. The first ambition is to document the consequences of the pandemic on the implementation of social policies at the cantonal level and to review the variegated practices and programmes deployed by local authorities in order to mitigate the impact of COVID-19 on vulnerable groups. Based on a documentary analysis and semi-structured interviews with experts and stakeholders, this first objective will result in a typology of local initiatives and adjustments to the pandemic. It will also provide us with key information to proceed with further analyses.2. Monitor the long-term effects of the pandemic on individual trajectories. Using sequence analysis, we aim to collect evidence on the effects of COVID-19 on the individual trajectories of social benefit recipients over a medium-term period. To do so, we will use administrative data sets to describe the diversity of trajectories of recipients of social benefits (including unemployment or disability benefits, social assistance and the so-called APG COVID) and compare their characteristics and dynamics before and since the pandemic. This will allow us to identify and monitor subpopulations that are particularly affected by the crisis and exposed to the risk of long-term unemployment and social assistance.3. Compare local practices and dynamics. The third objective relies on a fully integrated combination of qualitative case studies and sequence analysis at the cantonal level. The mixed-methods research design will allow us to contextualize and interpret quantitative results according to local circumstances and identify best practices in addressing the socioeconomic consequences of the pandemic. It will also provide us with a comparative and diachronic perspective that is currently missing in the literature.",,2026,Haute école de travail social et de la santé HES-SO,556183.53,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2023 +P27726,196906,"A Systematic Assessment of the Drivers of COVID-19 in the Swiss HIV Cohort Study: Epidemiology, Immunology, and Genetics","We propose to conduct a systematic study of seroprevalence, determinants of clinical outcome and potential preventive influence of antiretroviral therapy in people living with HIV (PLWHIV) during the COVID-19 pandemic utilizing the extensive sample and data collection of the Swiss HIV Cohort Study (SHCS). In a large, systematic plasma screen for the presence of anti-SARS-CoV-2 binding and neutralizing antibodies, we will be able to not only assess the seroprevalence of SARS-CoV-2 infection in over 2000 individuals but also elucidate many aspects of COVID-19 epidemiology, pathogenesis, and immunology. The comprehensive patient data that are available within the investigated patient cohorts will empower our study to perform extended systematic analyses that go beyond a mere frequency analysis of antibody responses but will also allow to identify factors associated with severity of disease and disease outcome. Moreover, it will allow us to gain information on future SARS-CoV-2 prevention strategies. Aim A: Defining seroprevalence and characterizing antibody responses against SARS-CoV-2 in the SHCSWe aim to assess the presence of anti- SARS-CoV-2 binding (A1) and neutralizing antibodies (A2) in the Swiss HIV Cohort study (SHCS). We will be able to assess experimentally reactivity against SARS-CoV-2, and cross-reactivity against the circulating coronaviruses (CoVs) and the past SARS and MERS epidemics. Comparing this to the vast experimental data generated for HIV binding and neutralizing antibodies [1-3] will allow for a multilayered understanding of the humoral response to SARS-CoV-2 and HIV in PLHIV. Moreover, with this thoroughly described cohort, we will be able to assess the demographic and epidemiological determinants of SARS-CoV-2 seroconversion within Switzerland. We will further investigate whether binding antibody responses also correlate with neutralization (A2). This will help us define whether binding is a predictor for neutralization and ultimately gain insights into responses relevant for vaccine efficacy. Finally, we will test the association between SARS-CoV-2 and the rich epidemiological, demographic, behavioral, and genetic data in the SHCS and thereby elucidate the drivers of the ongoing SARS-CoV-2 epidemic (A3). Aim B: Are there any protective effects of antiretroviral therapy against SARS-CoV-2?Based on the findings of Aim A we will assess the effect of antiretroviral drug efficacy on SARS-CoV-2 infection probability. This analysis will help us understand whether protease inhibitors do have potential as preexposure prophylaxis in SARS-CoV-2.Aim C: Systematic description of determinants of clinical outcome and reinfection in HIV/SARS-CoV-2 positive patientsWe intend to perform a detailed analysis of possible risk factors for the development and severity of COVID-19 (C1) and for re-infection of SARS-CoV-2-seropositive PLHIV (C2) in the SHCS by analyzing seroconversion and additional factors such as comorbidities, HIV- specific variables, human genetics, and co-medication.",,2022,Klinik für Infektionskrankheiten und Spitalhygiene Universitätsspital Zürich,329739.63,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Epidemiological studies | Therapeutics research, development and implementation | Vaccines research, development and implementation",Disease susceptibility | Disease surveillance & mapping | Prophylactic use of treatments | Characterisation of vaccine-induced immunity,2021 +P27727,212031,Scholars at Risk Application_Ukraine_Dr. Olena V. Cherniavska (Prof. Stefano Brusoni),"The idea that innovation and change are happening faster than ever has become a truism. In fact, the challenge is identifying those few things that -seemingly- are not changing at the same pace. This proposal builds on the observation that our teaching methods are indeed lagging behind the needs of students and educators alike. The COVID-19 pandemic made this lag very transparent. This proposal will focus three work-packages that aim at assessing how higher education institutions as well as corporate education entities are adjusting to the new normal. It aims at understanding what the 'new normal' actually is, in terms of balancing digital and physical training methods, and how this balance impact educational outcomes.",,2023,International Affairs Office of the President ETH Zurich,117603.59,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P27730,215306,"How did COVID-19 reframe end-of-life planning of older adults in Switzerland? Preferences, Communication, Knowledge, and Behaviors Regarding End of Life and End-of-life Planning before and during the COVID-19 crisis","Since the rapid spread of the Coronavirus Disease 2019 (COVID-19), older adults with and without preexisting medical conditions have been identified early as particularly vulnerable to the physiological effects of the virus. In Switzerland, public health policies for COVID-19 were especially targeting individuals aged 60 and over, as most of the COVID-19-related deaths occurred among this age group. The media also extensively covered the issue of COVID-19-related health and mortality risks, confronting everyone, directly or indirectly, with the topic of death and dying. The pandemic, thereby, also contributed to increasing public awareness about the use of invasive and intensive medical treatment such as medical ventilation or sedation, the complexity of medical decisions at the end of life (EOL), e.g., concerning withholding or withdrawing life-supporting treatments as well as possibilities to engage in advance care planning (ACP). In this context, older adults' perceptions and experiences regarding EOL health issues, including ACP or advance directives (ADs), may have changed. While editorials, commentaries, and viewpoints on the importance of promoting and implementing ACP & ADs during the COVID-19 pandemic have been booming in the scientific literature, only a limited number of studies have focused on the actual influence of of the COVID-19 pandemic on EOL-related outcomes in the general population to date. To address this gap in the literature, we aims to provide an update on older adults' EOL preferences, communication, health literacy, knowledge, and behaviors in the ""new normal"" since the start of the COVID-19 pandemic and their association with individuals' socio-demographic, regional, cultural and health characteristics. To this end, we will analyze existing and new (to be collected) data related to EOL planning of the Survey of Health, Ageing and Retirement in Europe (SHARE), a nationally representative survey of adults aged 50 years and older living in Switzerland. Specifically, we aim:1. To develop a questionnaire on EOL preferences, communication, health literacy, knowledge, and behaviors in response to the COVID-19 pandemic that also allows for assessments of potential changes in core outcomes based on longitudinal pre- and newly collected pandemic data;2. To explore the interplay between individuals' attitudes towards EOL and EOL planning before the COVID-19 pandemic and wellbeing and mental health during the COVID-19 pandemic;3. To explore the change or stability of EOL preferences within domains that are central to individuals' perceptions of ""healthy aging at the EOL"" and a ""good death"" before and during the COVID-19 pandemic;4. To explore changes in EOL communication with family members, close friends, and healthcare providers before and during the COVID-19 pandemic and to assess the acceptability of technology use for this purpose; 5. To explore the longitudinal trend of health literacy, EOL knowledge and EOL health literacy before and during the COVID-19 pandemic and to assess the digital health literacy skills after the first waves of the COVID-19 pandemic;6. To estimate the prevalence of ACP, including ADs, and to compare the estimates before and after the first waves of the COVID-19 pandemic.Building on the long-lasting expertise and previous work of our interdisciplinary team, the proposed project represents a unique opportunity to portray the role that COVID-19 played in reframing EOL planning in a population-based sample of older adults living in Switzerland. Besides its scientific impact, our research will also help to inform public health policies and intervention designs to improve EOL planning during these challenging times at both the individual and societal levels.",,2027,HEC - Ecole des Hautes Etudes Commerciales Université de Lausanne,684748.05,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2024 +P27738,206429,"RESPIRE : Reconnecting with Experience and Sensitive for instructional Practices fostering Inclusivity, Resilience and Equity.","This project investigates the question of the resilience of university instruction following the shock of physical and mental isolation into which trainers and learners were thrust during the COVID-19 pandemic. It constitutes a central issue insofar as everything suggests that digital interactions and hybrid teaching are here to stay. We defend the idea that the resilience of university environments, and of society, depends on a new balance between the inevitable use of digital tools and the place for sensitive experience and embodiment. The final goal is to empower teachers in higher education to face the new situations in various contexts. We seek to participate in the restoration of the synergy between the cognitive and the sensitive by: 1.Provide an overall picture of distance training practices implemented during the pandemic, in each of the partner institutions, in the disciplines concerned by the project.2.Explore hybrid experiential support as a space for in-action dialogue between teachers, learners, and knowledge, with a view to reducing inequalities in learning.3.Investigate the place of sensitive experience within a given context as a space for learning by taking into account embodied knowledge in a hybrid model.4.Provide material for the renewal of training practices, toward greater equality and inclusion, in various modalities, including distance learning.Through a partnership between Canada, France and Switzerland, we anticipate the following results: 1) a better understanding of the role of sensitive experience, effect of context and embodiment in pedagogical relationships and learning, 2) instructional schemes easier to adapt to differing modalities, in person and at a distance, and within different field realities, 3) the development of new knowledge in the research fields of sensitive experience and contextualization. Scientific writings from this project will be a source of inspiration for decision makers in charge of support university trainers.",,2025,HEP Vaud UER MU,198772.86,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P27742,202048,RNA-protein interactions at the host-viral interface of SARS-CoV-2 infections,"RNA viruses are a persistent threat to human health and have caused numerous public health emergencies in recent years. In particular zoonoses, the transmission of a virus from animals to humans, have epidemic potential when they are accompanied by the acquisition of human-to-human transmissibility, as it occurred for the recently emerged human coronavirus, SARS-CoV-2. A better understanding of the intricate relationship between host cells and viruses that goes beyond the innate immune response is fundamental to unveil the mechanisms that allow viruses to efficiently co-opt and reprogram cellular machineries for viral replication and adapt to new host species.This proposal will profile RNA-protein interactions at the host-viral interface of SARS-CoV-2 infections with a particular focus on the identification of host RNA-binding proteins (RBPs) that are instrumental for viral replication. Co-option of host RBPs has been demonstrated for a large number of RNA viruses and is essential for the successful completion of the viral life cycle. However, our current knowledge is mostly limited to single case descriptions in humans and lacks a comprehensive characterisation of host RBPs across different species that either promote or inhibit viral replication. In-depth profiling of such host-viral interactions during SARS-CoV-2 infection will give insights into host adaptation and lend a better understanding of the evolutionary consequences that arise from these interactions. In this proposal, we will profile the host-viral interface of SARS-CoV-2 infections by pursuing the following Aims:i) Characterisation of RNA-protein interactions and temporal dynamics of SARS-CoV-2 infection.ii) Functional characterisation of host-viral RNA-protein interactions and evolutionary consequences.iii) Comparative analysis of RNA-binding proteins between host species and impact on viral adaptation.The insights gained from the proposed work are of high relevance, not just during the current COVID-19 pandemic, but present an important foundation to better understand the biology and host adaptation mechanisms of RNA viruses. The proposed work will provide a characterisation of direct RNA-protein interactions during SARS-CoV-2 infection and identify host RBPs with pro- and antiviral properties, alongside their cognate binding sites across the viral genome. Taking the evolutionary consequences into account that arise from these interactions, the proposed work will identify nucleotide sequences within the viral genome that are under evolutionary constraint to maintain host RBP binding and will help to better understand and anticipate viral evolution. Furthermore, the evolutionary comparison of RNA-binding proteins between host species will identify endogenous RBPs acting as species-specific determinants of host range and give insights into how host RBPs influence viral adaptation. The immediate impact of this work lies in the identification of conserved viral sequences that can be used as target sites for RNA-based antiviral strategies and the identification and characterisation of host RBP interactions as potential new drug targets for SARS-CoV-2 infections. Beyond the specific insights that will be gained on the SARS-CoV-2 host-viral interface, this work will have important implications for our understanding of RNA viruses and their adaptation to new host species, with the potential to unveil host RNA-binding proteins as important players in viral host range.",,2025,EPFL-SV-GHI-LVG,968194.4,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis",2021 +P27745,198352,Enoxaparin for primary thromoprophylaxis in ambulatory patients with coronavirus: the multicenter randomized controlled ovid trial,"Background. Coronavirus disease (COVID-19) has emerged as a pandemic and a public health crisis of global proportions. One of the most frequently described poor prognostic features in patients with COVID-19 is the development of pneumonia and coagulopathy, reflected by an increase in D-dimers. Studies from Europe and Northern America suggested that not only venous thromboembolism represents the predominant vascular complications in COVID-19 patients, but also that its incidence might be higher than previously observed in other groups of patients admitted to hospital for acute conditions. Venous thromboembolism (VTE), encompassing deep vein thrombosis, lung thrombosis, and pulmonary embolism, can be the first clinical manifestation of COVID-19 caused by local and systemic inflammation, reduced mobility, hypoxia, endothelial dysfunction.In particular, the cumulative incidence of VTE in COVID-19 patients is approximately 20-30% (up to 70% in ICU patients undergoing VTE screening). Half of the VTE events, mostly PE, however, were diagnosed at hospital admission, suggesting that these events developed during the home quarantine.Recent guidance stated that prophylactic-dose LMWH, such as enoxaparin, should be considered in all patients who require hospital admission for COVID-19 in the absence of any contraindications. One of the better known non-anticoagulant properties of heparins, their anti-inflammatory function, include binding to inflammatory cytokines, inhibition of neutrophil chemotaxis and leukocyte migration, neutralization of the positively charged peptide complement factor C5a, and sequestering acute phase proteins: this may provide a benefit in COVID infection where pro-inflammatory cytokines are markedly raised and acute respiratory distress syndrome represents a feared and life-threatening complication.It remains unclear whether COVID-19 patients not admitted to the hospital due to non-severe clinical conditions should receive thromboprophylaxis and whether this provides a clinical benefit weighed against the risk of anticoagulant-associated bleeding. The evidence is scarce also for non-COVID-19 patients. The most recent American Society of Hematology (ASH) guidelines state that In medical outpatients with minor provoking risk factors for VTE (eg, immobility, minor injury, illness, infection), the ASH guideline panel suggests not using VTE prophylaxis (conditional recommendation, very low certainty in the evidence of effect).Research Question.We hypothesize that thromboprophylaxis with standard-dose low-molecular-weight heparin in symptomatic outpatients with COVID-19 may reduce hospitalizations and all-cause death by reducing the risk of developing coagulopathy and preventing thromboembolic events.Specific objectives.The purpose of this study is to show the superiority of ambulatory thromboprophylaxis with enoxaparin versus no treatment to prevent any hospitalization and all-cause death within 30 days of randomization in patients aged 50 or older with COVID-19. Key secondary objectives for this study are to determine if enoxaparin administration versus no treatment reduces specific cardiovascular and thromboembolic complications, namely venous thromboembolism, myocardial infarction or stroke, within 14 days, 30 days and 90 days of randomization and if this intervention is associated with a net clinical benefit, accounting for major bleeding events. Methods.The study will be conducted as an investigator-initiated, multicentre, randomized open-label controlled trial. In the study, a total of 1,000 adult patients aged 50 or older with COVID-19 and candidates to ambulatory treatment will be randomized to receive enoxaparin 40 mg sc once daily or no treatment for a total of 14 days. The primary outcome, a composite of any hospitalization or all-cause death, will be assessed within 30 days of enrolment. We implemented logistical solutions to integrate the process of SARS-CoV2 testing, pre-screening, screening (hot-line and flyers), in-hospital recruitment, enrolment, and randomization/allocation at five University hospitals and 2 large cantonal hospitals in Switzerland. A nationwide OVID Hot-Line telephone number will be made available in 3 languages (German, French, Italian) for interested patients or test centers to contact the Hot-Line. Standard procedures concerning privacy, discussion with patients on details of the study, collection of informed consent, and instruction on how to administer the study medication will be maintained in conformity with GCP recommendations. This will also include outcome measurements to be conducted by telephone with a standardized questionnaire.Having adopted a 'hard' primary outcome, hospitalization or death, and having extended the follow-up period up to 90 days, we aim to achieve two objectives: (1) obtaining uncontestable estimates of major clinical relevance, (ii) minimizing the potential reporting bias typical of open-label studies.Expected results and impact.As the vast majority of COVID-19 have been and are being treated in the outpatient setting, the results of the present study will have a major impact on the way this condition is treated and will be applicable to billion people, notably the most fragile part of the general population, worldwide. Beyond COVID-19, this study will investigate for the first time the concept of ambulatory thromboprophylaxis and represent the first large study on this topic.",,2023,UniversitätsSpital Zürich Klinik für Angiologie,1067449.1,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2020 +P27746,198363,Combined epidemiological and molecular investigation of 3 nosocomial outbreaks of SARS-CoV-2 cross-infection,"Background and rationaleDuring the Coronavirus disease 2019 (COVID-19) pandemic, 3 nosocomial outbreaks occurred in distinct sites in the Department of Rehabilitation and Geriatrics of Geneva University Hospitals. After enhancing infection prevention and control, the outbreaks were successfully controlled. Protection of healthcare workers (HCWs) is a key priority whilst caring for severe acute respiratory syndrome (SARS-CoV-2) infected patients. Similarly, preventing healthcare-associated COVID-19 among COVID-19 negative patients is key. Particular attention should be placed on vulnerable patients in long-term care facilities and geriatrics. In the outbreaks we describe, the complex interplay between and respective role of HCWs and patients in transmission remains unclear. Aim and objectives The overarching objective of this study is to reconstruct the outbreaks in each hospital site (A, B, C) combining epidemiological with genetic data, in order to understand transmission dynamics and improve infection control practices and consider additional preventive strategies.Specific aimsSpecific aims of the study include:•Compute the attack rate in the institution among patients and HCWs•Establish viral transmission pathways of the outbreak and reconstructing a transmission tree•Identify the directionality of transmission (i.e. HCW to HCW, HCW to patient, patient to HCW, community to HCW)•Identify risk factors for healthcare-associated SARS-CoV-2 infection and mortality among patients •Identify risk factors for HCW SARS-CoV-2 infection •Describe and analyse variation among infection control practices across the 3 sites•Identify and develop new strategies to prevent healthcare-associated COVID infection Study design and expected resultsThis is a retrospective cohort study of COVID-19 clusters involving 104 patients and 185 HCWs in 3 distinct hospital sites of the Geneva University Hospitals. We will obtain clinical and epidemiological data of all SARS-CoV-2 positive patients and HCWs. We will construct epidemic curves by ward for patients and HCWs, and compute attack rates and doubling times. These data will help to construct a putative transmission tree. We will perform a nested case-control study in one of the sites that will seek to establish risk factors of HCW infection by SARS-CoV-2. Exposure to COVID-19 patients and other HCWs is assessed, as well as potential community exposure. A nested case-control study will be performed in order to identify risk factors for healthcare-associated SARS-CoV-2 infection among patients, and a case-case-control study to identify risk factors for mortality among these patients.SARS-CoV-2 complete genome sequences will be generated using an amplicon-based next generation sequencing protocol. Complete viral genomes will be obtained after mapping reads to a SARS-CoV-2 reference sequence. We will combine epidemiologic and genetic data using the ""outbreaker"" package in R software. We will use a Bayesian framework, which will combine the distribution of the generation time, from which a probabilistic transmission tree is constructed, as well as a model of sequence evolution along the transmission chain. We will impute generation times from estimates available from the literature. The output from the model will allow us to estimate the dates of infection, mutation rates, multiple importation events, missed cases, as well as to reconstruct the transmission tree. Expected impactAnalysis of these nosocomial outbreaks will provide key insights into transmission dynamics of SARS-CoV-2 in the healthcare setting and will inform infection prevention guidelines in order to enhance protection of HCWs and patients. Furthermore, this study will demonstrate the added value of genome sequencing in elucidating the complex connectivity of SARS-CoV-2 dissemination in hospitals.",,2022,"Infection Control Program Hôpitaux Universitaires de Genève Faculté de Médecine, Université de Genève",273112.38,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease susceptibility | IPC in health care settings",2020 +P27747,196197,Retrospective case-control study nested in a seroepidemiological investigation: multi-level assessment of risk factors for SARS-CoV-2 seroconversion among healthcare workers in a Swiss tertiary care hospital,"Introduction: Healthcare workers (HCWs) are vulnerable and should be adequately protected against SARS-CoV-2. To date, we do not know the impact of specific infection control practices or exposures of HCWs on their acquisition risk of SARS-CoV-2, as tested by highly sensitive serological tests, which are already used in epidemiological studies of coronavirus acquisition and transmission. Our institution will conduct a self-funded prospective longitudinal seroprevalence survey, in order to evaluate the cumulative incidence of infection and seroconversion among HCWs, the fraction of asymptomatic infection, and estimate the level of herd immunity at the hospital level. This survey represents an ideal platform to conduct a nested epidemiologic study on HCW risk factors and exposures.Objective: To evaluate risk as well as protective factors, and compare the influence of various types of and adherence to infection control measures targeting SARS-CoV-2 on the risk of seroconversion among HCWs, controlling for the intrinsic exposure risk in different hospital working areas (high vs low risk areas).Population: Retrospective case-control study nested in a longitudinal repeated seroprevalence survey of a convenience sample of HCWs working at Geneva University Hospitals, stratified by profession and recruited in the seroprevalence survey, including nurses and physicians dedicated to areas at low risk and high-risk of exposure to SARS-CoV-2. Case will include all HCWs seropositive for IgG specific anti-SARS-CoV-2. Control will include all HCWs seronegative for IgG specific anti-SARS-CoV-2. Three controls will be selected for each case.Collected data: Individual-level data: (1) Triweekly serum samples for serological testing. (2) Questionnaire regarding demographic data, in-hospital and community exposure history, infection control practices, and symptoms suggestive for COVID-19. Aggregate-level data: (3) Infection control practices (standard precautions, contact and droplet precautions, environmental hygiene) (4) Staffing workload (nurse acuity index, occupied beds, length of stay) (5) Contamination pressure (cumulative incidence of infection by SARS-CoV-2 per unit)Statistical analysis: Factor associated with seroconversion will be analyzed a secondary mixed-effect multivariate logistic regression after pre-selection of pertinent variables using forward stepwise method and clinical pertinence. Time varying exposure will be explored in a secondary analysis comparing cases seroconverted already at baseline, and newly seroconverted cases during follow-up periods. Significance: Assessment of risk or protective factors for SARS-CoV-2 seroconversion among HCWs might help improving control of nosocomial transmission, protecting both HCWs and patients. Using a serological test will preclude the strong misclassification bias present in studies using molecular tests based on symptoms to determine cases, providing a much more complete and robust picture of the epidemiological situation. Ultimately, we aim to strengthen infection control capacity in such overwhelming viral outbreak situations.",,2021,"Infection Control Program Hôpitaux Universitaires de Genève Faculté de Médecine, Université de Genève",70111.21,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control",Immunity | Disease susceptibility | IPC in health care settings,2021 +P27757,206469,Reduction and Replacement of animal models for antiviral testing using 3D human respiratory epithelia,"The use of animals in preclinical drug testing is a matter of public interest, as it often involves suffering and discomfort. Animal models not always predict human responses, as argued by those who oppose in vivo research. Laboratory animals exist as inbred lines to increase the statistical power of preclinical tests. For each human disease there are several strains, that often produce inconsistent results, as observed for SARS-CoV-2 mouse models. Besides, this range of models does not reflect the clinical variety of human patients, not allowing to pinpoint differential disease development to find new cures. It emerges from this scenario that more accurate and standardized in vitro models should systematically complement animal models. The ongoing pandemic offers the unique opportunity to implement preclinical studies. The lack of medications after SARS-CoV-2 outbreak forced the healthcare systems to repurpose drugs based only on preclinical tests run in cell lines. Some drugs then failed clinical trials, while others displayed in patients a profile similar to that observed in cell lines, implying that tests in animals may be partially replaced by in vitro approaches. Three-dimensional (3D) tissue culture models offer a compelling complement to animal use, because they can be developed from human cells, thus improving the translation of the results to humans. In agreement with the 3R principles, we propose 3D human airway epithelia (HAE) as a complement to in vivo systems, for the testing of antivirals. Cultured at the air-liquid interface, HAE reproduce the architecture, the composition and the barrier defense mechanisms of the in vivo epithelium. They are reconstituted from human primary cells in serum-free medium, thus reducing the use of animal-derived components. The main asset of HAE is that they permit to study the original pathogenicity of clinical viral specimens, which would be lost using immortalized cell lines. Also, they have a significantly longer lifespan compared to other 3D systems (such as ex vivo lung slices or organoids) and can be used to characterize the long-term effects of the manipulations. HAE represent an ideal system to test antivirals targeting respiratory viruses. They are polarized and antiviral administration from the air-exposed apical or liquid-exposed basal side nicely mimic the in vivo air-borne or blood-borne incoming pathway. To implement the Replacement and Reduction principles, we present a multidisciplinary project involving virology, pharmacology, single cell genomics and machine learning. Our goal is to assess the power of HAE, in comparison to mouse models, to predict in humans the toxicity and efficacy of antivirals against respiratory viruses. We will pursue this goal in the context of SARS-CoV-2 infection. Specifically we will 1) determine, in HAE and in mice, the non-toxic dose-range of a collection of antivirals used in clinical trials as SARS-CoV-2 therapeutics; 2) determine the efficacy and the molecular effects of the antivirals against the most relevant SARS-CoV-2 variant, in HAE and in mice, by single cell RNA-sequencing (scRNA-seq); 3) develop a machine learning framework to minimize the number of preclinical tests in mouse models based on the toxicity and efficacy readout in HAE.",,2026,Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève,1128833.91,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Disease models | Pre-clinical studies,2022 +P27764,201113,Crafting life for health and well-being: Understanding different types of crafting in everyday life and in challenging times (Craft4Health),"Background and rationale: An intensified and increasingly demanding working life, accelerated by the COVID-19 pandemic, requires new approaches to improve health and wellbeing at work and beyond. Job crafting is a well-established strategy to lower work demands, increase resources, and achieve better person-job fit and meaningful work. In this project, we broaden this perspective of proactively shaping work life to include also boundaries between life domains and off-job time.Overall and specific aims: The overall goal of our study is to better understand how the different forms of job crafting, off-job crafting, and boundary crafting are related and form patterns of crafting, as well as to examine predictors (i.e., stable, situational, and crisis-related) as well as health and well-being related outcomes of single and combined crafting behaviors. We study these processes and relationships across three different time frames: (1) long-term (3-month periods; digital surveys), (2) short-term (daily; ecological momentary assessments across one workweek), and (3) crisis-related (digital survey before and during the COVID-19 pandemic).Expected results: Based on a broad, diverse sample, our research project will result in new theoretical and empirical insights on the crafting process over time (i.e., antecedents and outcomes) and on the interrelationships of crafting efforts in different life domains. In addition to these new scientific insights which will be published in high-quality academic journals, the practical implications will be communicated via policy briefs and the general media. Impact: In the new flexible (tele)working life, life domains increasingly overlap and a holistic view on life, including both work and leisure, is urgently needed. Our project will pave the way for creating a more meaningful and sustainable (working) life in which employees take an active role in aligning their environment with their personal needs, preferences, and abilities. Beyond this project, our findings will directly inform the parallel development of hybrid crafting interventions combining in-company training and digital tools (websites & smartphone applications).",,2024,Gesundheitswissendchaften und Medizin Prävention Universität Luzern,664428.96,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P27768,196348,Large-scale testing and tracking of SARS-CoV-2 infection and evolution by deep sequencing,"The global pandemic of Coronavirus infectious disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an acute and global health challenge of a magnitude not experienced in over a century. To combat the COVID-19 pandemic, countries are relying on non-pharmaceutical interventions (quarantines, social distancing, shutdown of non-essential businesses), which are having a dramatic social and economic impact. A central problem is the lack of diagnostics and surveillance capacities, which are essential for detecting SARS-CoV-2 infections and subsequently reducing transmission chains through effective NPI. Current molecular diagnostics (qRT-PCR assays) are limited in throughput (e.g., 7'000 total per day in Switzerland) and do not provide viral molecular sequence information for epidemiology.To overcome the limitations in current COVID-19 testing, we will develop a molecular barcoding method to tag individual patient RNA samples, which will then be highly multiplexed and tested for detection of virus by deep sequencing and bioinformatics. The importance of molecular barcodes is that they will be connected to a patient identification sample, meaning that on a single deep sequencing run (e.g., Illumina MiSeq) we will be able to multiplex and test up to 4,800 patient samples (Aim 1). Furthermore, our deep sequencing-based testing assay will also allow us to perform evolutionary analysis; by selectively sequencing regions of viral diversity, we will obtain molecular sequence information tracking the spread and evolution of the virus throughout Switzerland (Aim 2). This sequencing data will then be used to recreate transmission chains and inform further quarantine and social distancing measures. Our preliminary estimates suggest that we can sequence 4,800 samples (50 distinct 96-well plates) within a single MiSeq run in less than 24 hours. This can easily be scaled up based on the number of available patient samples by either increasing the number of sequencing runs in parallel (across multiple machines) or by using a higher throughput sequencing machine. This simple molecular biology assay can also be transferred to almost any diagnostics lab in the world, within Switzerland there are at least 30 sites where testing centers could be established and the sequencing infrastructure is available to likely achieve 2,000,0000 samples per week. With this capacity, it would only take 4 weeks for all of Switzerland to be tested for SARS-CoV-2 infection.",,2022,"Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich",315052.5,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen genomics, mutations and adaptations",2020 +P27771,198293,"Psychosocial and health impacts on refugees caused by living in overcrowded camps and by the Covid-19 pandemic: disease profiles and barriers in access to health care - a mixed method cross sectional convergent study in Moria refugee camp Lesbos, Gre","The aim of this research project is to assess psychosocial and health impacts on refugees caused by living in overcrowded camps and the Covid-19 pandemic and to explore and identify current physical and mental health problems and barriers to adequate healthcare for refugees in camp Moria (Lesbos). Since Moria is one of the largest and most overcrowded camps in Greece there is an urgent need to assess the current situation so as to tailor public health measures that meet local needs. In contrast to previous studies, which mainly investigated disease profiles from the healthcare provider view, we would like to examine different stakeholder`s viewpoints, particularly refugees themselves. We believe this approach enables us to receive comprehensive and diverse answers to our study objectives, that would otherwise remain hidden. Despite the general knowledge about the prevalence of communicable diseases in refugee camps, little is known about their origin (imported/transmitted within the camp) nor about the prevalence of Covid-19, especially in large, overcrowded camps. Furthermore, past research mainly focused on lack of medical staff or communication barriers in access to healthcare, but there is no information regarding which type of diagnostic tools and therapies are lacking in order to provide adequate healthcare services. Assessing all of this lacking information, is crucial for giving guidance to different stakeholders on implementing needed public health measures to prevent the spread of disease, protect the health of the community and improve patient outcomes. This in turn can also provide a relief for limited medical resources. Furthermore, the identification of stress and resilience factors of refugees can help to reduce stress during the stay in refugee camps and to strengthen their resilience and thus health. We hope that the findings of this research will not only benefit refugees staying at Moria, but might be transferred to other refugee camps worldwide, giving them guidance on the type of public health measures and research studies needed. This mixed method study consists of three phases with specific objectives in each phase. Phase 1:- To assess disease profiles of refugees: type and frequency of communicable and non-communicable diseases.- To identify barriers to medical care: communication, availability of medical staff & resources, frequencies in which available diagnostic and therapeutic options were sufficient or insufficient to diagnose or treat the patient. Identification of resources, diagnostic tools and medication, which are most urgently needed.Phase 2:- To examine, which laboratory tests are available at the hospital in Mytilene and which were frequently used to diagnose communicable diseases in 2020. To assess the frequency and results of testing for SARS-CoV-2 among refugees at the hospital in Mytilene since February 2020.Phase 3:- To examine the psychosocial impact of the Covid19 pandemic and of the stay in Moria camp. - To assess the perceived level of physical and mental health by the refugees during the stay in the camp in general and during the pandemic.- To assess symptoms of anxiety, depression and stress.- To identify current needs, stress factors and barriers in access to healthcare.- To identify factors affecting the development of psychological distress and resilience.- To identify most frequently used coping strategies.- To analyse associations between psychological coping methods, exposure to social media, physical and mental health background, demographic and psychological variable Outcomes.Methods:We plan to conduct a mixed methods cross sectional convergent study design, which will allow us to investigate upon the study objectives from different stakeholder`s viewpoints. Phase one will concentrate on the treating physicians viewpoint by examining medical consultations carried out by NGO`s during the medical field work in Moria camp. Phase two focuses on laboratory resources of the local, public hospital in Mytilene, which is run by the government and ministry of health. The third phase will provide insights into the perceptions of physical and mental well-being of refugees in Moria camp by conducting a survey among them. Phase 1: We will screen, during a period of three weeks, all medical consultations of the three different healthcare providers in Moria camp (one with mainly GP services of general and chronic diseases, one with children and mental health care services and one with emergency care services). Screening will take place one full week per health care provider and will be carried out by a physician, who attends and only documents the medical consultations and, after each consultation, assesses a short one minute questionnaire survey (open and closed questions) with the treating doctor about the working diagnosis of each case, diagnostic certainty and diagnostic and therapeutic resources. Phase 2: Screening of laboratory records of refugees for the execution and results of SARS-CoV-2 tests at the hospital in Mytilene between February and October 2020. Additionally we will conduct a short questionnaire survey with staff of the Mytilene hospital laboratory concerning the availability and frequency of the application of test methods to detect different communicable diseases in 2020. Phase 3: We will conduct a survey with refugees, who live in Moria. The Survey will be available in different languages and will be programmed on to tablets, which will be handed over to the participant to fill out the survey with assistance by trained study assistants. Participants will be recruited during the waiting time for medical consultations in case the patient does not have a very urgent problem and at central places in Moria camp (e.g. at central cloth washing stations). Furthermore, there will also be postings in the camp, on which a link to the survey can be seen in the respective language, so that refugees can fill out the questionnaire online independently. These methods are chosen in order to provide a sample of refugees from the camp, as representative as possible.Expected Outcomes:We expect to increase the knowledge about current disease profiles of refugees in Moria and about the prevalence of locally transmitted diseases, where we anticipate the prevalence of communicable diseases to be higher than shown in previous studies among different refugee populations, as Moria is an overcrowded camp and because of the worldwide Covid-19 pandemic. Furthermore, we expect to identify current barriers in access to adequate healthcare, where we anticipate the lack of personal, diagnostic and therapeutic resources be high. Thereby a regional action plan will be developed to address locally existing barriers and health problems. Additionally, we expect to receive an overview about the perceived level of physical and mental health by refugees and to identify stress factors and actual needs during the stay in the camp in general and during the pandemic. Furthermore we anticipate to identify regional mental health problems and high levels of psychological distress of refugees caused by living in an overcrowded camp or by the pandemic and to identify the underlying factors and most frequently used coping strategies. We will gain knowledge upon the actual psychosocial impact of the Covid19 pandemic and of the stay in a large, overcrowded camp and upon the underlying factors and associations. This enables us to create an action plan with priorities, which need to be addressed to improve the mental well-being and examples of projects/ public health measures to address these priorities.This research will provide, in the Greek context, evidence that will underpin better selection and development of adequate public health measures, leading ultimately to an improve in access to adequate health care services and a better prepared medical and public health workforce, thus improving refugee`s health status.",,2021,Universitäres Notfallzentrum Inselspital Universität Bern,20317.3,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P27800,198281,"New insights into the COVID-19 pandemic: Genetic polymorphisms, role of SLC6 amino acid transporters, renal aspects and therapeutic perspectives","This project has been designed to aid deciphering biological and pharmaceutical aspects of the SARS-CoV-2 virus pandemic. As the pandemic progresses, it becomes apparent that there are large variations in clinical outcomes among patients, with significant country differences. Besides risk factors such as age, diabetes, arterial hypertension, cardiovascular disease, lung disease and chronic kidney disease, genetic variants in the angiotensin-converting enzyme 2 gene (ACE2), which encodes the virus receptor, the TMPRSS2 gene encoding the protease which cleaves the viral spike proteins, and the ACE2-associated amino acid transporter gene SLC6A15, likely affect SARS-CoV-2 infection and the risk of developing severe COVID-19 clinical manifestation. Using a combination of biochemical assays such as micro-scale thermophoresis (MST) to determine SARS-CoV-2 receptor binding domain (RBD) binding affinity to ACE2 and the SARS-CoV-2 pseudovirus entry assay to reveal viral load, we propose to clarify the roles of specific allelic variants of these genes in conferring COVID-19 severity, including their gender relevance and to screen for blockers of viral susceptibility as hit/lead compounds for the development of novel treatment strategies. The Specific Aims of our proposal are as follows: 1) Biochemical investigation of the effects of genetic variants of host cell targets such as ACE2, TMPRSS2 and SLC6 family members on SARS-CoV-2 RBD binding affinities and infection susceptibility; 2) investigation of the association of amino acid transporters of the SLC6 family (SLC6A14, SLC6A15 and SLC6A19) with ACE2 in lung, intestine and kidney epithelial cells and examination of their effects on SARS-CoV-2 infection; 3) screening preselected target-focused compound libraries using MST, looking for ligands that prevent SARS-CoV-2 binding; and 4) final validation of hit/lead compounds and findings on genetic polymorphisms. We expect that this project will provide straightforward new deliverables that fit in well with the goals of this NRP 78 COVID-19 Call.",,2023,Abteilung für Nephrologie Medizinische Universitäts-Kinderklinik Inselspital,675411.84,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2020 +P27804,208388,"humansofpandemics, A transmedia exploration of the experience of pandemic","This Agora project is the public-oriented extension of the ongoing FNS project <>. The goal of this research is to document and understand the relational disorganization and emotional turmoil that we have been through, both as individuals and as community members. The Covid-19 pandemic and the protective measures taken to cope with it have been sometimes seen in a negative way. A part of the population has felt forgotten or even sacrificed and has expressed distrust of scientist and other experts. To avoid the worsening or weaponizing of these tensions, it is crucial to communicate to the public but also to invite it to actively participate in a public inquiry. This is the main goal of our humans of pandemics project (HOP). Thought of as a multi-site, transmedia experiment, the HOP project intends to link the elaboration of a documentary to a ""multilayered"" website, as well as an Instagram and a Facebook account, in order to explore different channels of communication and to facilitate the participation of diverse types of publics. It is designed as follows:1)a three-level website, humanofpandemics, whose first level has already been completed, which aims 1a) to collect testimonies and to make portraits of different social universes through first-person accounts (probationer, director, prostitute, musician, embalmer, etc.) 1b) to engage the public in dialogue about those testimonies via social networks (Instagram and Facebook) 1c) to give access to the public to the elaboration of an ethnographic documentary, with the different steps, choices or dilemmas explained in a logbook 2)the elaboration of a documentary on a concern that has proved to be recurrent in the testimonies we collected: << what is really essential? >>. This topic is transversal enough to address fundamental sociological questions, such as identity recognition, forms of life and division of labour. The public will be invited to participate in the making of the documentary and to put itself in the shoes of the ethnographer 3)the organization of events, in particular 3a) discussions and conferences on our website 3b) the screening of the documentary on the stage of various national and international documentary film festivals 3c) the organization of screenings in different social environments, followed by discussions on the content but also on the very process of constructing a sociological inquiry In summary, this project aims to create a kind of digital agora, which invites the public to testify but also to seize sociological tools in order to conduct their own investigation into the pandemic and its social and psychological consequences. This collaborative transmedia experiment is not designed as an asymmetric process of popularization, intended to pass along a pre-established body of knowledge to an ignorant public. It is has been designed as multi-dimensional public space that rests upon a cooperative exchange between researchers, research participants and the general public. The presence of the public is implemented in the whole HOP architecture. In fact, this project aims to experiment a new collaborative research method, which encourages researchers to go beyond classical observation and interviews. This method is a new way of conducting sociological research because it integrates digital technology, not only as an object of research but also as a tool of sociological research. Social networks will be here of first importance to relay the website, share information on research, collect testimonials, gauge the public's interest, test which media work best, receive feedbacks. In shot, this HOP project does not consist of a sociology of the digital ; it is a digital sociology whose very essence is to be connected with the public.",,2024,Institut des sciences sociales Faculté des sciences sociales et politiques Université de Lausanne,158395.65,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2022 +P27805,196185,Social distancing in times of pandemics. A study of the renegotiation of the interaction order,"Extremely difficult for various reasons, the pandemic crisis also creates a kind of large-scale experimental laboratory of our social conducts, which must be the object of extensive, multi-site, interdisciplinary and collective research. In order to narrow down the multiple possible lines of investigation, this project has chosen to focus on the short-term and mid-term consequences of the imposition of << social distancing >> for preventing the propagation of the Covid-19. Although necessary for sanitary reasons, social distancing has indeed tremendous consequences from an interactionist standpoint - strongly inspired by Erving Goffman and Georg Simmel's theory of relations in public and interaction order. It has emptied public places and makes public encounters and a fortiori public gatherings legally punishable and, above all, morally reprehensible. While coexisting with strangers in a public space was synonymous with civility, it has suddenly become a sign of incivility and moral fault. Withdrawal into the private sphere and its concretely disaffiliative side has become synonymous with a more abstract affiliation, changing the true sense of the imagined community we belong to. Interaction avoidance and self-isolation have become signs of civility. With the epidemic, relations in public are proscribed, the order of interaction totally dislocated. Of course, social distancing would better be described as spatial, physical distancing. Mediated interaction can still take place in networked forms of communication and compensate for the absence of bodily copresence by amplifying the strange << absence presence >> proper to distant modes of interaction. It remains to know whether the multiplication of hybrid forms of mediated communication can suffice to alleviate the disappearance of the public space. Getting a glimpse at the short-term and long-term implications of the disappearance of the concrete public space over the conception of social relationships but also of oneself is at the heart of this project. Its main goal is to follow in real time the diachronic unfolding of the collective ongoing experience of << social distancing >> that everyone is currently making. To do so, we will collect data from a large network of informants from different socioeconomic backgrounds and from two countries, Switzerland and France. Two kind types of data will be collected. Confinement data: 1) micro-observation of public interactions in supermarket and on the street, necessarily limited by coronavirus restrictions, but also observations of the << left-behinds >> of confinement, migrants or poors that cannot isolate and protect themselves or others 2) (auto)ethnography of << stay-home >> interactions, mediated or not, which can consist of media reports as well as social media snapshots. We have already started this data collection by creating a collective diary in order to compare it, later on, with the post-confinement reconstruction of events and experiences. Post-confinement data: 1) observation of public interactions in supermarkets and on the street in order to see how interpersonal distance is renegotiated and proxemics has evolved 2) 30 non-directive face-to-face interviews with a sample of participants from different socioeconomic backgrounds. The first aim of this data collection program is documentary: it aims at generating ethnographic material and long lasting memory of << what happened to us >>. Its second aim is to delve into the << strategies >> put into place by people from a diversity of socioeconomic backgrounds in order to maintain sociality despite the necessity of social and physical distancing.",,2023,Institut des sciences sociales Faculté des sciences sociales et politiques Université de Lausanne,308843.5,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P27815,213852,COVID 19 vaccine uptake in children: understanding health inequities by using routine data,"Vaccinating children is widely described as crucial step to end the COVID 19 pandemic.Surveys showed important inequities: Vaccine hesitancy was higher in persons from socioeconomically disadvantaged backgrounds and persons originating from certain regions of the world. The aim of this study is to describe the vaccine uptake in Ontario in immigrant and non-immigrant children for the adolescent and the pediatric vaccine campaign. We would like to test the main predictors for vaccine uptake in children and adolescents who are migrants and children of migrants (second generation). The study is designed as a retrospective population-based cohort study. Children meeting the following criteria are included in the study: children 1) in possession of an Ontario health Card issued no later than on January first, 2021 2) living in Ontario since the beginning of the pandemic and 3) aged 4 to 17 years on January, first 2021. For all study participants, a database with the sociodemographic and clinical variables will be created using linked administrative health and demographic data at the Institute for Clinical Evaluative Sciences (ICES). Around 10 integrated databases will be used including the national COVID vaccine database, the COVID infections registry, the chronic disease registries, the Permanent Resident Databases and the Census database and the primary care and maternity databases.Crude rates will be compared using standardized differences. Negative binomial models will be used to explore predictors of immunization status. We expect a study population of about 2.5 million children and adolescents. Of those, about 25% will be children of migrants (second generation) and about 6% immigrants. We expect to detect important health inequities in the uptake of COVID 19 vaccines in children In Ontario. We hypothesize that the strongest predictor of vaccine uptake in migrant children is the region of birth. The results of this study will help to detect important health inequities. The results of this study will help to tailor future vaccine campaigns better to the needs of migrant children and children of migrants.",,2023,Notfallzentrum fuer Kinder und Jugendliche Inselspital,25742.86,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2022 +P27818,210142,Covid-19 policies and inequities in adult wellbeing: Building back fairer from the pandemic in Switzerland,"The Covid-19 pandemic has revealed the stark interconnections between social and economic inequality, health equity and population health. The pandemic has also made it obvious that despite their effectiveness in reducing transmission, Covid-19 measures have broader societal impacts on multiple dimensions of wellbeing including income, social participation, and mental health. Some studies have shown that the health and socioeconomic impacts of the pandemic are unequally distributed across income, education, ethnicity, and gender, and studies suggest complex impacts on income inequality. However, there is limited understanding of the causal mechanisms by which specific Covid-19 legal and policy instruments increase social vulnerability, reinforce pre-existing inequalities, and generate new forms of inequities in wellbeing. In addition, few studies have explored the effectiveness of government relief programmes to address these impacts in Switzerland.This project aims to address this gap by examining the equity impact of policies adopted in response to the Covid-19 pandemic and exploring the complex trade-off between public health policies, social policy responses and inequities in wellbeing. Our goals are to understand the causal impact of Covid-19 policies and government relief programmes on indicators of wellbeing, identify inequities in these impacts across socioeconomic groups, and carry out in-depth research with policymakers, health care professionals and vulnerable populations to understand these impacts and their integration in practice. To achieve this goal, we propose an interdisciplinary research programme involving law, economics, socio-anthropology, social policy, epidemiology, and social medicine. The project proposes to integrate quantitative and qualitative approaches across three levels: the legal and policy framework, professionals and institutions, and the general adult population. The project aims to provide policy-relevant evidence and tools to help decision makers account for the potential equity impacts of policies in response to major epidemics and societal shocks. The combination of disciplines and methodological approaches will offer a unique lens to understand the complexity of mechanisms by which Covid-19 policies influence inequities in wellbeing. The specific objectives of the project are:•To adopt an equity lens to analyse key laws in response to the Covid-19 pandemic at the national, cantonal, and international level;•To assess the causal impact of Covid-19 policies and government relief programmes on inequities in wellbeing and underlying causal mechanisms using quasi-experimental methods, by linking data on policies and laws at the national, cantonal and international level to longitudinal data of working-age and older adults;•To understand how Covid-19 policies influenced the wellbeing of highly vulnerable populations through in-depth qualitative interviews with health professionals and vulnerable individuals attending social and health services in the Canton of Vaud;•To examine societal preferences on the trade-off between competing objectives associated with the Covid-19 pandemic (e.g., reduction of transmission vs. overall wellbeing goals of the welfare state);•To understand how vulnerability was detected and managed in practice and ultimately propose concrete actions to improve future pandemic response.The project is structured around four interdependent, interdisciplinary work packages (WPs). In the first two WPs, we will use legal analysis (WP1) and quasi-experimental methods (WP2) to analyse the impact of health and social policy responses to the Covid-19 pandemic with an equity lens. This is complemented by a socio-anthropological study on the impact of measures in specific populations (WP3), and a qualitative examination of the trade-offs and triage logics underlying the detection and management of vulnerabilities among healthcare professionals, policy makers, and the general population (WP4). These activities will inform the development of an equity framework and toolbox for policy assessment and design, in close collaboration with our policy and implementation partners.The project is designed to contribute to the following programme objectives: 1) explicitly consider and transparently report the complex consequences of policies; 2) contribute to the better proactive management of future pandemics; 3) understand to what extent individual and societal wellbeing is affected by a pandemic and identify the best solutions to preserve them.",,2026,DESS Unisanté Université de Lausanne,444529.44,Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2023 +P27821,216772,Renewal_Scholars at Risk support for Tetyana Vereshchahina,"LECON: Learning co-configuration in hybrid teaching and learning environmentThere have been recent changes in the education system all over the globe due to COVID-19 outbreak. Hybrid learning has become an optimum solution for teaching and learning during a pandemic when various degrees of course hybridization allow students to stay home and resume in-class learning when it is possible. However, besides the indisputable benefits of hybrid learning, our literature review demonstrates the scientific gap between what is designed and organized by teachers and what is performed by students due to socially situated learning nature when students, being active participants of the learning process co-configure the tasks, methods, modes, and tools. This is why the present project is focused on the students learning experience in hybrid teaching and learning environment. The research framework grounds on the HY-SUP typology of hybrid learning systems that consists of six types of hybrid course designs and offers a mixed-method methodology to define and evaluate the effects of student's co-configuration of the course on learning outcomes in each of the types. Specific objectives of the project are: 1) to describe course design types according to the HY-SUP typology; 2) to describe students' co-configuration in six course designs; 3) to understand learning co-configuration performed by students according to representations of hybrid learning environment and cognitive characteristics. Understanding and describing these issues will help to improve the hybrid learning environment and adapt it more to nowadays' students' needs. This gives possibility to come closer to the process of learning in hybrid learning environment, to stay focused on the process and the results of learning.",,2024,Dienststelle für internationale Beziehungen Universität Freiburg,67420.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P27845,196245,Immediate and pre-emptive therapies for SARS CoV-2 positive and negative patients with high risk for Covid-19 pneumonia: Immunocompromised Collaborative Host Swiss Cohorts Based Trial Platform Initiative,"Background Endorsed public health measures have confined the SARS-CoV-2 pandemic in Western Europe but leave due to very low herd immunity a high proportion of the population at risk of infection. In a not unlikely second epidemic routine and repetitive PCR testing is essential for at risk populations for complicated SARS-CoV-2 for infection protection and monitoring. It is less clear, whether preventive treatment in individuals with Covid-19 infection with mild symptoms or in those uninfected but at high risk of complicated SARS-CoV-2 infection may offer additional protection against complicated SARS-CoV-2 infection. Methods We will set up a trial platform which will be implemented and nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study to investigate during a new epidemic the comparative effectiveness of immediate and preventive therapy with emerging antivirals against SARS-CoV-2. Patients in these cohorts with mild SARS-CoV-2 infection with no pneumonia and SARS-CoV-2 negative patients at risk for complicated infection due to age, HIV (<350-500 CD4 cells/µl), solid organ transplantation or with risk factors for COVID-19 pneumonia who consent to participate in the trial will be randomised to candidate antivirals. The primary composite endpoint is CT-confirmed pneumonia, hospitalization or death from any cause. Need for immediate hospitalization for any reason is an exclusion criteria. Based on accumulating evidence of ongoing and published trials of antiviral drugs against SARS-CoV-2 infection, patients will be randomized in the presence of one active drug to drug A versus control, in the presence of two drugs to drug A or B or control. Interim analyses are planned to adaptively randomize patients to the most effective comparator arm (intervention duration 18 months). Arms may be suspended for ineffectiveness and new arms may be added to the trial as novel therapies emerge. Interventional drugs will be selected by expert panels from both cohorts with provision of external up-to date evidence from meta-analytical reports. Relevance The project intends to establish a trial platform that is nested into existing cohort infrastructure to investigate the comparative effectiveness of early and preemptive upcoming antiviral therapies to prevent complications from SARS-CoV-2 in two very vulnerable patient populations. The chosen innovative trial designs allows for rapid trial implementation in case of a second epidemic and in the absence of an effective vaccine. The trial platform can be easily extended to involve further Swiss (or international) cohorts and will serve as an ideal instrument for potential future pandemics.",,2023,Institut für klinische Epidemiologie Universitätsspital Basel,314778.26,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase) | Therapeutic trial design,2020 +P27851,215891,Food System Optimization for Maternal and Child Nutrition in Zambia,"Building nutrition-sensitive and resilient food systems is crucial for a healthier world. A high proportion of rural households in sub-Saharan African countries are classified as being severely food insecure with sub-standard diet diversity which affects the overall health of people (Fraval, S, 2019), particularly children under the age of five. In Zambia, the food system is based on a few staple crops such as maize, cassava, millet, sorghum, and sweet potatoes and a couple of legumes - groundnuts and soybeans. Maize is by far the most important crop both in terms of sale and consumption. Maize accounts for 53% of the total cultivated area in the country and is grown by almost 90% of the 1.5 million smallholder farm households in the country (IAPRI, 2019; Mofya-Mukuka, R. and Hichaambwa, M. 2016). Typically, maize forms a large part of the diet, while nutrient-rich foods such as legumes, animal-source proteins, fruit, and vegetables are eaten in smaller quantities, particularly amongst the most impoverished families who are unable to provide a proper nutrition to their children. Despite periodic surplus maize production, most households have weak resilience to weather and market shocks. Seasonal hunger is widespread, leading to perpetual food insecurity. Given that maize production is dependent on the rainfall, food availability has remained highly vulnerable to weather shocks and other natural or health disasters coupled with output market instability. When rainfall is low or too high, most of the smallholder farm households' livelihoods are decimated, and incomes are drastically reduced. For example, during the 2021/2022 farming season, Zambia experienced floods in northern region, which left approximately 1.5 million people in need of relief food between October 2021 and March 2022. Other factors that contributed to the food insecurity are outbreaks of pests such as the African Migratory Locusts and Fall Armyworms. Food prices also remained higher than the five year average due to stifled supply chains as a result of COVID-19 restriction and food inflation pressures. In such situations, women headed households are particularly more vulnerable, owing to their fewer livelihood options (Mofya-Mukuka and Hichaambwa, 2017). The rural poverty level in Zambia is as high as 70%, and 46% of the Zambian population is estimated to be undernourished (IAPRI, 2019; USAID, 2019). The prevalence of stunting and wasting in the country remains unacceptably high, with stunting rates exceeding 35% and only 12% of the children meet the minimum acceptable diet (CSO et al., 2019). Stunting in children has long term effect including diminished cognitive and physical development, reduced productive capacity and poor health (WHO, 2014). In this regard, the protein amount and diversity are of great importance. Ensuring a high protein quality in the role of child development starts already with focusing on the role of the maternal diet. A protein and energy restriction has severe consequences. Intrauterine growth retardation is linked with being shorter, lighter, and weaker at adolescence (Ashworth, 1998). In contrast, the consumption of a high percentage of energy from protein during the early stages of pregnancy increased the birth body and placental weight (Moore et al., 2004). In childhood, an adequate protein intake is important for growth, and it was demonstrated that protein restriction decreases the levels of insulin-like growth factor 1 in healthy children (Smith et al., 1995). Therefore, it is especially important that the protein amount and quality are assured, especially when there are mostly plant-based proteins consumed such as maize. Improving the protein diversity goes in line with improving the diet diversity and can be a promising approach to improve the nutritional situation.While the nutrition and agricultural policy in Zambia recognizes the need to increase and diversify the production of nutritious foods, there has not been any systematic examination of local food systems and how to optimize them. Food systems must be transformed to make nutritious foods more easily accessible, affordable, and available all year-round. If food systems are unable to ensure regular supply of and access to food commodities, food insecurity is expected to increase both in the rural and urban centers, and malnutrition is likely to worsen. Because of the complexity of food systems, which encompass aspects such as agricultural output, socio-economic factors, food availability and accessibility, and a thorough examination of diets and nutritional factors, transdisciplinary research is imperative to achieve optimal results which after the end of the project, have the potential to be scaled at the national level. To that end, the proposed research is expected to inform and guide policy investment priorities for promoting sustainable and resilient food systems to enhance the availability and affordability of a wide variety of nutritious foods for making a healthy diet possible. This research project seeks to close the research gap in nutrition-sensitive agriculture and food systems and is relevant for development, as it addresses food systems and will identify pathways to improve them from an agronomic, socio-economic and nutrition perspective to achieve a high and direct improvement on the lives of mothers and children in food insecure environments in Zambia. The goals of the projects are aligned with SDGs 1, 2, 3, 5 and 10. Resilient local food systems and sound nutrition-sensitive recommendations will allow the target population to have regular access to diverse, high-quality nutrition and support healthy child and maternal diets. The problem of food insecurity and malnutrition in the Zambian food system is multidimensional and will be approached through a transdisciplinary, agricultural, socio-economic, and nutritional perspective. By carefully examining and addressing these multidimensions in the context of optimizing the access to dietary diversity and protein quality, the long-term sustainability and impact is assured. By the end of the third year of the project, agricultural and nutrition recommendations will be made to ensure a higher nutrient and protein bioavailability, in addition to other nutrition-sensitive measures. Because the research project will rely on the knowledge of local experts and the target population, appropriate and effective nutrition interventions for women of reproductive age and children will be sustainable and context specific.The overall goal of the project is to identify, recommend and implement interventions for optimizing food systems for maternal and child nutritionThe project specific goals are: 1. To map the local food system and determine which are the critical factors necessary for enhancing the resilience of the local food supply, including agronomic, socio-economic, and environmental aspects.2. To identify options for building a diversified and resilient nutrition-sensitive food systems which minimize food insecurity among mothers and children in the western region of Zambia.3. To develop appropriate and effective policy recommendations and interventions for optimizing maternal and child nutrition in the face of climate change and other external risks.",,2026,Agronomy HAFL Berner Fachhochschule BFH,4485.15,Human Populations | Other,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2023 +P27852,218863,Scientific exchange: Prof Ian Nell - Practical-theological research in a culture of digitality,"Prof. Ian Nell and Prof Thomas Schlag are in close academic contact since about 15 years. Currently we are conducting intensive collaborative research in the research framework of the so-called CONTOC (Churches Online In Times of Corona)-research project, which started in 2020 and is now in its second phase (https://contoc.org/de/contoc/). The CONTOC research project aimed from the beginning at an empirical, representative survey of the development and implementation of especially digital church practices and programs under the conditions of COVID-19. As academic partners and partner institutions from Practical Theology we analyze comparatively what can be learned from these experiences for the future church work and practical-theological research in the context-specific cultures of digitality in Switzerland and South Africa. We are now at the point that we want to do intensive comparative work, investigating the specific situations, political frameworks and ecclesiologies in both countries. We have previously already conducted intensive studies on questions of a public church, public theology and the question of the self-understanding of church communities and pastors in the transformation and post-apartheid society of South Africa. This CONTOC-research project is connected with two other focal points for exchange:On the one hand, this relates to Schlags leadership of the University Research Priority Program ""Digital Religion(s). Communication, Interaction and Transformation in the Digital Society"" (2021-2032) (www.digitalreligions.uzh.ch), in which the digital practice of religious individuals and communities is investigated in an interdisciplinary manner. Due to the strong developments of digital religious practice in South Africa as well it is expected to gain considerable benefit from the insights of this research consortium for further studies in South Africa as well as for productive academic collaboration. On the other hand, the Zurich Centre for Church Development (ZKE), directed by Schlag, with its research on the transformation of church practice, is also of considerable importance for comparative ecclesiological reflection. Against the background of the current developments of digital religious practice of Christian communities and congregations in both countries, we will deal with the question of the phenomena of digital transformation and make the first elaborations for a corresponding international-comparative essay. As a background for this content-related and methodological elaboration, contacts will be established and strengthened with various members of the URPP research consortium as well as with members of the Centre for Church Development (ZKE). These insights shall also help for structuring the further exchange between both practical-theological departments. As during earlier study trips (in 2012 and 2019) from Switzerland to South Africa, we will also use this scientific exchange for intensive preparations of student exchanges and courses within the framework of the study trip planned for 2024. In the best case scenario, these joint encounters and experiences can also lead to opportunities for academic qualification work, whether at Master's or doctoral level, and maybe even a third-party-funding initiative.",,2023,Theologisches Seminar Universität Zürich,8746.06,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P27855,197297,Overtourism? Cities count.,"In the current context of the overtourism controversy in European cities, a controversy which could be exacerbated by the role of human mobility in the Covid-19 health crisis, the argument of numbers is central. This controversy broke out with the emergence, from 2015, of criticism, demands and resistance from the inhabitants of certain highly touristy European cities against tourism, finding in opposition those who think that tourism is positive, even necessary, in particular for the economy, which must be openly reinforced and promoted. In this controversy, the statistical argument is often put forward. However, it comes up against an inability of managers and residents to reconcile political arguments and statistical arguments in a context of increased mobility. At the same time, new statistical systems are emerging, that of big data and the attempt by many players to quantify using digital traces. With the Covid-19 crisis where tourism is temporarily stopped, we have a particularly good time to study the way in which the statistical argument is used to point towards ""overtourism"" or towards ""undertourism"". >.Our research project has two objectives: 1. Observe the way in which the statistical argument around tourism is used by cities and their citizens, whether by arguing in favor of overtourism or in favor of undertourism or any other dimension which would appear relevant; 2. Test the hypothesis of the advent of new forms of tourism governance of cities (""smart cities"" or others) linked to the development of big data in order to identify the ""governmentality"" which would correspond to it. To do this, we study on the one hand the production of the figures mobilized in the current controversies in four European cities and, on the other hand, the political uses of the statistical argument (for the growth of tourism? against mass tourism ? against certain forms of tourism? as electoral leverage?). As byproduct, we will end up with an unprecedented mapping of the sources of statistical production on tourism, useful for understanding the phenomenon and which will be able to inspire producers and users of these figures. From a theoretical point of view, two disciplines are called upon: on the one hand, on the other hand, the sociology of quantification which studies the conventions and practices of ""numbering"" in a constructivist epistemology and their political dimensions (Desrosières, 2014); on the other hand, geography which constructs tourist cities as a scientific object but which also studies the controversies around overtourism through the specific input of the territorial relevance of the quantification (district, scale, extension, etc.). From an empirical point of view, the case studies will concern: a) cities affected by tourism in an unequal manner and where the controversies around tourism are different: Venice and Lucerne, where the debate around overtourism is in full swing; Paris (emblematic metropolis from a tourism point of view) and Lyon (a secondary metropolis whose economic strategy is partly based on tourism); b) the respective national statistical contexts whose specificities will be presented and discussed, in order to highlight their own local quantification systems; c) the global context, with the study of the World Tourism Organization (WTO), among others. The methodology developed is that of the disciplines involved: sociological interview and observation linked to the process of statistical production (choice, data processing), its social character (actors), and its political use, i.e. << who >>, << how >>, << why >> data. The spatial dimension will also be taken into account due to the three scales treated (international, national, urban/district) and in the notions of mobility and flow that tourism presupposes.",,2025,Institut de Géographie et de Durabilité Faculté des Géosciences & de l'Environnement Université de Lausanne,515199.56,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P27863,196396,Governing systemic crises in the 21st century: Learning from early Covid-19 responses in Europe,"The current COVID-19 crisis is causing widespread disruption in health, economic and social systems worldwide. School have been shut in many countries. International travel has been badly affected and supply chains have been interrupted. The response to this ongoing pandemic is unprecedented. Countries have introduced containment measures assorted with restriction of movements that apply to numbers of people never seen in recent history. Many countries are focusing their effort on mitigation strategies to protect the elderly that seems particularly vulnerable to the COVID-19. In addition, as stressed by the Director General of the World Health Organization on 19 March 2020, ""all countries must strike a fine balance between protecting health, minimizing economic and social disruption, and respecting human rights"". Over the past couple of decades, globalization and growing interdependencies have created new opportunities and benefited the many. The human civilization has never sustained so much people on the planet with such level of access to basic human needs. These progresses come also with challenges including the rapid propagation of disturbances originating in one area of the global society (e.g. health) to multiple sectors and levels of governance. The financial crisis of 2008, the Ebola crisis in West Africa in 2014-2015 and now COVID-19 are examples of systemic crises that can threaten modern societies. The impact of and response to this ongoing crisis can be understood within a framework that account for the strengths and fragilities of different systems, i.e. their resilience. Based on insights from the governance of complex systems and resilience, this project aims to assess the initial impact of and responses to the current COVID-19 systemic crisis from an interdisciplinary perspective combining insights from public health, economics and law. In particular, the project seeks to understand how different European countries cope, adapt and transform in the face of systemic disruptions such as those caused by the rapid dissemination of COVID-19 across Europe. Overall, the goal is to gain an understanding of what is affected during times of crisis, their interdependencies, and how we can improve the resilience of our governance systems.",,2022,Global Studies Institute Université de Genève,295574.51,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts,2020 +P27865,208385,The constant flows: Experiences and stories of the COVID-19 pandemic,"The purpose of this project is to set up an exhibition, taking place in Geneva from February 13th 2023 to April 28th 2023, where visitors will be able to interact with researchers from the Geneva School of Social Sciences (University of Geneva), in order to learn and debate about some aspects of the Covid-19 pandemic consequences in society. The exhibition will involve several activities, some targeted at a general audience, some more specifically prepared for classes of high-school students, who will come with their teachers to meet our researchers.",,2023,Département de Sociologie Faculté des Sciences de la Société Université de Genève,198404.5,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2022 +P27880,201840,Revealing environmental drivers influencing the abundance of the Rift Valley fever virus vector Culex mosquito,"Rift Valley fever is a neglected mosquito-borne viral disease caused by the Rift Valley fever virus (RVFV). Rift Valley fever outbreaks result in illness in humans, as well as in high mortality and abortion rates among domestic animals, hence subsequently impacting humans' livelihoods leading to severe socio-economic losses and increased poverty, especially in already vulnerable communities. Rift Valley fever presence is affected by the presence of it's mosquito vectors, however the drivers of mosquito vector presence and abundance are complex. Environmental factors such as climate, soil properties and the anthropogenic influence on land use have been identified as varying drivers of the population dynamics of RVF vectors such as the Culex spp, subsequently impacting the disease spread and outbreaks. To decrease RVF epidemics and therefore reduce the burden of disease for human and animals lives and livelihoods further understanding of the complex environmental balance of Culex spp mosquito populations is necessary. In my proposed scientific exchange with Dr. Melinda Rostal and Dr. Whitney Bagge from EcoHealth Alliance, over three months, I aim to build on my previous experiences gained through my research on Rift Valley fever in Chad (manuscript currently in preparation) during my PhD and to investigate the relationship between environmental factors and the population dynamics and abundance of RVF-relevant mosquito species from the Culex genus in South Africa. Precisely, with the proposed scientific exchange my four main aims are; 1) to reveal environmental drivers of the RVF vector Culex genus mosquito population abundance, 2) to enhance my analytical and critical thinking skills in the interface of human, animal and environmental health, 3) to increase my credibility and visibility within the scientific community by co-authoring on a peer-reviewed international publications resulting from the proposed scientific exchange, and finally 4) to connect and collaborate with the international network of One Health researchers at the EHA and their partners. I will work on already collected data encompassing 30 distinguishing environmental factors on soil properties (mineral densities, humidity), vegetation, climate and weather (precipitation, wind direction and speed), as well as data on Culex abundance. Overall as first step I will conduct a literature review to reveal the most frequently investigated environmental factors for explaining Culex spp abundance thus far. Herewith I will gain a profound overview of already existing investigated associations between environmental factors and Culex abundance, which will help me prioritize my existing data for the analysis. I will further investigate the data quality, conduct data cleaning if necessary and determine data characteristics (i.e. distribution of data) of the environmental and Culex specific variables. Finally, I will investigate the statistical model that fits given variables and explains the Culex spp abundance best, depending on the data characteristics and literature review. Options for appropriate models include: zero-inflated negative binomial and Poisson's regression models. After deciding on the appropriate model methodology I will model the Culex abundance as a function of the combination of previously selected environmental varaibles. I hypothesize that environmental drivers such as climate, weather, soil property and vegetation are significant drivers of Culex mosquito abundance. I expect that the analyses of environmental factors impacting the abundance of the Culex spp will provide evidence for better understanding ecological drivers of the RVF disease outbreaks and hence support future predictions of epidemics. On a global view, my work through the proposed scientific exchange will be integrated into the other RVF vector work and together I believe they will provide valuable information to other researchers and policy makers working towards reducing human and animal illness and decreasing socio-economic losses caused by RVF in affected vulnerable communities. I further expect to immensely develop my analytical modelling skills in and knowledge on infectious disease research, to enlarge my scientific network and community through my inclusion within EHA's network and their external partners and to increase my visibility and credibility within the international scientific community by co-authoring on a peer-reviewed scientific publication.",,2021,Veterinary Public Health Institute Vetsuisse Faculty University of Bern,10852.98,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Animal and environmental research and research on diseases vectors,Vector biology,2021 +P27883,220491,Improving outcomes in persons with long COVID-related fatigue using energy management education: A target trial emulation study,"Background: There is limited evidence for managing persons with post-COVID-19 condition, also known as long COVID, due to the unappreciated nature of this disease. One of the most common symptoms is fatigue, experienced mainly as severe, impacting cognition with extended activities of daily living and social activities (Sivan, Parkin, et al., 2022), which causes significant distress and disability to the affected individual and prevents them from returning to previous life routines, work, and social life (Townsend et al., 2020). Recommendations based mainly on the opinions of experts and patients' lived experiences underline the need for a multidisciplinary approach that includes self-management education, peer support, and symptom management strategies (NICE guideline, 2022). Energy management education (EME) (Hersche, Weise, Michel, Kesselring, Barbero, et al., 2019) is a manualized, evidence-based occupational therapy (OT) peer-group self-management education for persons living with chronic disease-related fatigue, developed to be implemented in the Swiss health care context. After the first COVID-19 wave, several institutions in Switzerland started to use the EME protocol and its materials in their OT services for persons with long COVID. At the Clinic for Neurorehabilitation Basel (REHAB), EME is part of a multidisciplinary rehabilitation program for persons with long COVID. In 2022, we conducted a feasibility study at REHAB with a pre-post design to investigate the effect sizes and procedural and methodological issues of a future clinical trial. Aims: The purpose of this project is three-fold. The primary aim is to evaluate if adding EME to standard care improves outcomes in persons with long COVID-related fatigue. The secondary aim is to explore the energy management behavior strategies applied in daily routines after participating in EME and investigate the influencing factors of implementing behavior changes. The third aim is to perform a cost-effectiveness analysis of EME. Methods: This is a two-arm prospective interventional study with a target trial emulation approach. The estimated sample size to guarantee 90% power is 122 (61/61). Participants in the experimental group will follow in addition to standard care interventions (e.g., physiotherapy) EME at three research sites (USZ, REHAB, and INSEL). The control group is selected from a pool of persons living with long COVID-related fatigue by their propensity score and matched 1:1 with persons in the experimental group. The control group receives the standard of care, including any rehabilitation intervention, except OT-based EME in the peer groups. Four self-reported questionnaires document the outcomes of interest at baseline (BL; week 0), after lesson 7 (T1; week 7), post-intervention (T2; week 15), and at follow-up (T3, week 24). The primary outcome is self-efficacy in performing energy management strategies. The secondary outcomes are the impact of fatigue, competency in performing activities of daily living, and health-related quality of life. At T3, behavior change in the energy management survey will collect data on stable used behavior strategies and perceived influencing factors. A cost-effectiveness profile of the experimental intervention will be performed. Expected results and impact: This study will deliver urgently needed data on the effectiveness of an intervention recommended by guidelines for managing persons with long COVID. Furthermore, the results will contribute to evidence-based self-management education in persons with chronic fatigue syndrome and other chronic conditions. OTs will gain more detailed insight into the behavior changes after EME, which will support coaching and offer a more informed perspective to persons with long COVID. Data from the cost-effectiveness analysis will provide rehabilitation managers, assurances, and policymakers with data for informed decisions regarding group-based rehabilitation interventions.",,2027,2rLAB DEASS SUPSI,560340.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Clinical trials for disease management | Health financing,2024 +P27884,196359,The Covid-19 Pandemic : Measuring the impact of global health threats on border controls,"This research project examines the legitimacy of political communication regarding the incisive restrictions imposed on international and national mobility as well as social distancing as the global crisis provoked by the Covid-19 pandemic is unfolding. In view of their important political, economic and social implications, including for civil liberties, these restrictions demand for a heightened level of political legitimacy in order to be effective and to avoid a health crisis to develop into a political crisis. This research project examines the factual and normative arguments advanced by political actors, their timeliness, internal consistency and external congruence in three European states (France, Switzerland, UK) in connection with relevant international actors (EU, WHO, UN). This is done on the basis of an extensive dataset coding political communication on mobility restrictions on social media (Twitter), through press releases and in parliamentary debates from early 2020 to summer 2021. Juxtaposing political communication with political decisions, and triangulating the assessed legitimacy of political discourse with existing public opinion surveys and effective epidemic developments, the project will identify the conditions under which mobility restrictions imposed in European citizens have been communicated in an effective and legitimate manner, and under what conditions political communication has led to contestation and politicization. Particular attention is paid to the ways in which political actors appeal to notions of national versus European and/or international solidarity and identity, and how actors coordinate their discourses across national, European and international institutions. Eventually, this research will explain whether and why the Covid-19 pandemic has deepened existing social cleavages in European societies, and under what conditions such divides have been avoided.",,2023,University of Geneva,112594.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Social impacts | Other secondary impacts,2021 +P27885,198428,Agent-based tracking of disease spread with dynamic models of travel behaviour in a pandemic,"Epidemic models are essential tools to coordinate all aspects of the response to pandemics. Models can inform policy makers on strategies for vaccinations and testing, but also to trigger mitigation measure such as the 'lockdowns' encountered during the COVID-19 outbreak. However, historically epidemic models have relied on crude approximations of infections processes such as the spread of droplet between individuals over space, and time. Here, we propose to use and further develop a well-established technology -agent-based models of daily travel behaviour- to simulate epidemics with considerably increased resolution. These models produce by design a network of encounters between individual agents (people, vehicles, etc.) at very high spatial (e.g. the bus used by the agents, or the church visited) and temporal resolution (each second of the day). The technology enables tracking chains of infections, as well as the health status of all agents over time. The strength of the approach lies in the diversity of behaviours that can be attributed to agents, which in turn enables to simulate a wide range of targeted policies: timing, duration, and spatial extent of containment policy, but also restrictions specific to age, professions, etc. Agents can be generated with any attributes, as long as suitable conditional distributions are known, e.g. morbidity by sex, frequency of home-office by income level, or mobility tool ownership (e.g. car, season ticket etc.). Since September 2019, the IVT is tracking the travel behaviour of a panel of 1,200 persons providing a unique insight in their behavioural response. We have detailed calibrated agent-based and activity-based simulations of daily life available for Switzerland and the region of Basel. The existing models that have originally been developed to simulate transport will be supplemented to incorporate detailed epidemic transitions in collaboration with the epidemiologists on the team (""episim""). Concretely, we propose to address the following questions. After a careful initial and then continuously updated calibration we will first simulate activity-focused containment policies against COVID-19 with 4 versions of the transport model. The measure of effectiveness for each policy will be defined jointly with the team, but will likely focus on intensive care occupancy, acute COVID-19 cases, days lost to illness, and days lost to quarantine measures. Confidence intervals will be calculated for each effectiveness metric. •Phase 1: Current agent- and activity-based average workday models including detailed vehicle-based public and private transport simulation.•Phase 2: Integrate a weekend implementation of the Switzerland model which also includes new arrivals and departures from/to abroad and inclusion of small children. •Phase 3: Integration of the behavioural adaptations in response to the constraints imposed and in response to the risk assessment of the agents.•Phase 4: integration of the interactions within the households and social networks to capture spatial mixing of the population.Second, we will compare results of the analysis of the four models against epidemic surveillance data, and against the output of traditional epidemic models based on differential equations. The comparison will focus on COVID-19 cases and intensive care hospitalizations for the following situation: ""Backcasting"" (reproduction of previous epidemic), as well as ""Forecasting"" with and without therapeutic medical interventions and contact tracing. In addition, we will develop dashboards to allow non-experts to interact with the simulations (hospital administrators, general public, etc). From a practical perspective, this proposal aims to optimize the current response to COVID-19, by exploring complex and spatially-heterogenous policies (Cantons and trinational regions with border effects). Our results will also be relevant for preparedness against other pathogens with pandemic potential. Finally, this proposal will also address a fundamental question in disease modelling: what are the respective merits of the 'traditional' equation-based models vs 'new' agent-based models in terms of projection accuracy, parametrization, and computational cost.",,2023,Institut für Verkehrsplanung und Transportsysteme ETH Zürich,1107892.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Epidemiological studies | Policies for public health, disease control & community resilience | Health Systems Research",Disease transmission dynamics | Impact/ effectiveness of control measures | Policy research and interventions | Health information systems,2020 +P27888,196190,COVID-evidence: a living database of trials on interventions for COVID-19,"Background: The COVID-19 pandemic is characterized by an unprecedented urgency to obtain reliable information on therapeutic options and their evaluation in clinical trials.Objective: We aim to provide a freely available and continuously updated online database of worldwide trial evidence on benefits and harms of interventions for COVID-19, including interventions for prevention, diagnosis, treatment and clinical management.Data sources include literature databases (e.g. PubMed), trial registries (e.g. ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform (WHO-ICTRP) and Chinese Clinical Trial Registry (ChiCTR)) and preprint servers (medRxiv and bioRxiv).Selection criteria: We will include reports, registry entries, and manuscripts of trials testing any intervention actively allocated to humans with COVID-19. We will include a broad range of trial designs (including multi-arm but also uncontrolled trials) and interventions (including drug and non-drug treatments, vaccines, diagnostic procedures, and decision algorithms) without restrictions to language, region, or healthcare setting. Design and Methods: In close collaboration with a world-wide network of partners, we will use a multi-method approach combining peer-reviewed search strategies, continuous automated extraction of search results, automated classifications combined with crowd-based manual screening and data extraction, and quality control through expert review. We will start with a set of core variables and gradually expand the amount of information based on the needs of different stakeholders (including patients, clinicians, systematic reviewers, guideline developers and policy makers). The new website COVID-evidence.org will provide both the extracted information and links to the original data sources. The modular design of the database will allow continuous updates, addition of new data sources and content, and flexible adjustments to future projects.Relevance of the project: COVID-evidence.org will continuously monitor the clinical trial research agenda on COVID-19 and present decision-makers and researchers with the latest available trial evidence on how to prevent, diagnose, treat and manage COVID-19. Finally, by including key experts in the field and catalyzing international collaborations, we aim to foster evidence-based decisions on all levels of health policy and practice.",,2022,CEB Universitätsspital Basel,184865.02,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Health Systems Research",Therapeutic trial design | Vaccine trial design and infrastructure | Health information systems,2020 +P27892,201493,Tracking Health,"""""Tracking Health,"" or in German, ""Der Gesundheit auf der Spur,"" is not only the motto to which the Epidemiology, Biostatistics and Prevention Institute (EBPI) of the University of Zurich has dedicated itself and for which the approximately 200 employees of our institute work every day, but it is also the motto of our Open Day planned for 19 June 2021. At this event, we will open our doors to families living in Switzerland and specifically, those of the canton and city of Zurich. We not only want to show them who we are and what contributions we make to a healthier Switzerland, but, above all, to be in direct contact and dialogue with these most important 'clients'. During the Open Day, we will lay the foundation for an exciting exchange by means of innovative formats. For example, we are planning a health trail, which will be set up as an exhibition course with 31 different booths. At the booths, our visitors can test and experience health, but above all will have the opportunity to ask our top qualified and experienced scientists questions or share personal health-related knowledge, insights or experiences. There will also be a central program focusing on the Corona Pandemic, in which our institute is heavily involved with research, a COVID-19 test center and as support of health policy. In the professionally-moderated program, infectious disease experts, medical historians, epidemiologists, biostatisticians and other public health experts will review and evaluate the Corona experiences of the past months, share their experiences and, of course, interact directly with local citizens.We will develop an efficient safety concept in order to protect our employees as well as our anticipated 2000 visitors from possible Corona virus infection. In order to make the event a great pleasure for young and old as well as for our staff, the planning commission will develop a professional project management and communication plan which will involve important partners and stakeholders of the institute. Of course, if the pandemic situation is unstable and regulations by the Swiss Federal Office of Public Health advises against larger events in June 2021, we will postpone the Open Day to a later time point.This very special day is intended to build a bridge between the public, our stakeholders and public health scientists by showcasing current topics from everyday life in a health research context. We are looking forward to an exciting day for all involved EBPI collaborators, partners and visitors.""",,2022,Gesundheitswissendchaften und Medizin Prävention Universität Luzern,53456.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Community engagement | Health service delivery,2022 +P27893,212203,Symposium on IGOs Initiative in Time of Crisis,"This symposium aims at presenting the results of a research on International Governmental Organisations (IGO) in time of crisis. The research reviewed the practice of 'Initiatives' by IGOs when responding to crises or the unforeseen needs of their respective membership. It forms part of a broader research project on the role of IGOs in international law where more than 100 initiatives were identified so far, focusing on 14 IGOs. The notion of an IGO's initiative, conceptualised as activities of the Executive Heads and the Secretariat's staff that enhance the remit of an organization beyond those functions initially or formally envisaged by its constituent instrument, is examined. A descriptive analysis of over 30 initiatives demonstrate that they may be successful in addressing modern unforeseen challenges, whether they stem from international emergencies, climate change, dynamic technological advancements, or global health crises such as the COVID-19 pandemic- especially when such initiatives are accepted and supported by IGOs' members.",,2022,Département de droit international public Faculté de droit Université de Genève,7839.25,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2022 +P27906,196641,Longitudinal single B cell studies across the trajectory of COVID-19 to identify SARS-CoV-2 specific monoclonal antibodies and long-term memory formation,"The development of neutralizing humoral immunity is suggested to play a pivotal role in the protection from COVID-19 and the generation of immunological memory is basis for future protection from the disease. However, to date, the genetics of the acute and memory B cell response are unknown, few potential neutralizing monoclonal antibodies are described and the capacity of humans to develop B cell memory against SARS-CoV-2 is still elusive. Here we will prospectively and longitudinally follow a cohort of (>200) healthcare workers at the intestinal diseases department of the University Hospital Bern. By monitoring the course of SARS-CoV-2 infection status in this cohort, we will assess their acute and memory B cell response before, during and after COVID-19 infection. We have ethical permission to sample peripheral blood of consenting personnel and measure SARS-CoV-2 viral status weekly using in-house diagnostics with consumables that are designed not to conflict with the clinical lab pipelines. By determining the single B cell repertoire in the periphery before the onset of clinical or virus-positive disease we will be able to determine the immunological baseline for each study participant at single cell level. This baseline will be compared to acute and memory B cell populations during the active disease to identify hallmarks of the B cell repertoire associated in patients with asymptomatic, mild or severe COVID-19 infection. After resolution of the infection, subjects will be sampled at various timepoints up to half a year and the potential hallmarks of the B cell repertoire will be identified in the peripheral memory B cell pool. The data will provide a description of the acute B cell response to SARS-CoV-2 at single cell level and can determine if cellular B cell memory is formed in COVID-19 infection. We hypothesise that the data will be able to describe immunogenetic determinants of the B cell response that can discriminate between protected from non-protected individuals and/or severe from non-severe cases. Further, it will create a resource that will contribute to global databases guiding potentially neutralizing SARS-CoV-2 monoclonal antibodies.",,2022,Universität Bern,288277.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P27913,198470,cGAS-STING-mediated self-DNA sensing in COVID-19 immunopathology,"Covid-19 is a major public health threat that has already caused more than 200,000 deaths worldwide. Most patients only experience mild-to-moderate upper respiratory tract symptoms, but 10 to 20% progress to severe disease with pneumonia, acute respiratory distress syndrome (ARDS), and systemic endothelitis affecting multiple organs including kidney, heart, brain and skin. Evidence suggests that severe disease is driven by a dysfunctional immune response characterized by excessive inflammation. Accordingly, anti-cytokine therapies have triggered huge excitement for the treatment of Covid-19. However, current data from ongoing trials suggest only limited clinical improvements. Identifying the molecular driver(s) underlying the hyperinflammatory response in Covid-19 is therefore vital to provide and rationally design new and more efficacious therapies. The central hypothesis of our proposal is that aberrant activation of the cGAS-STING pathway - the dominant innate sensing system that recognizes DNA as a danger signal - is a key pathogenic factor in Covid-19-associated immunopathology. We hypothesize that the cytopathic effect of the virus on epithelial and endothelial cells promotes cell death with accrual of extracellular DNA, which is then internalized by infiltrating macrophages, unleashing the fatal inflammatory response via activation of cGAS-STING signaling. Our hypothesis is based on three observations: (i) cGAS-STING is a major sensor of tissue damage and COVID-19 pathology is associated with widespread epithelial and endothelial cell destruction; (ii) bats have evolved a non-functional STING gene, which allows them to withstand tissue stress during flapping flight and may explain their ability to host coronaviruses in the absence of pathology; (iii) COVID-19 associated skin lesions demonstrate transcriptional hallmarks of COVID-19 pathology and resemble skin lesion of SAVI, a monogenic disease caused by activating mutations in STING.Our proposal will test this hypothesis with three aims. In Aim 1 we will determine whether cGAS-STING is activated in COVID-19 pathology. To this end, we will use COVID-19 derived skin lesions, which are common, readily accessible for biopsies, and, most important, demonstrate a striking molecular and phenotypic overlap with inflammatory processes in the lung. Using these clinical samples, we will perform extensive immunophenotyping, transcriptome expression profiling, virus visualization by electron microscopy, and analysis of cGAS-STING activation. In Aim 2 we will dissect the mechanism of cGAS-STING pathway activation by SARS-CoV-2 infection using complementary in vitro cell culture approaches. The goal is to establish the contribution of cell-intrinsic versus cell-extrinsic mechanisms leading to cGAS-STING pathway activation in infected and bystander cells, respectively. In Aim 3 we will pursue proof-of-concept studies on the efficacy of pharmacological inhibition of STING to attenuate SARS-CoV-2 immunopathology using two pre-clinical models of SARS-CoV-induced pneumonia.",,2022,Service de Dermatologie et Vénéréologie Département de Médecine Hôpital de Beaumont - CHUV,658852.33,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Disease pathogenesis | Pre-clinical studies",2020 +P27921,206409,16th Alpine Brain Imaging Meeting (ABIM) 2022,"We apply for financial support for the 16th international winter conference on Brain Imaging in Cognitive and Clinical Neuroscience, called ABIM, that we organize in January 9-14, 2022 in Champéry, Switzerland. The SNF kindly supported the previous editions of this annual meeting by financing travel and accommodation costs of the invited keynote speakers.Last years meeting was cancelled due to the Covid pandemic, but most of the speakers who agreed to participate in the 2021 edition agreed to come in 2022 instead. The first ABIM meeting took place in 2006. The meeting lasts for 5 days and always takes place in the same period (mid January) in Champéry. This tradition makes the meeting well recognized in the scientific community in Switzerland, Europe, and worldwide. It is usually attended by 150-180 researchers in the field of clinical and cognitive neuroscience and neuroimaging. It brings together worldwide leaders in the field as well as many junior researchers from Switzerland and abroad. The structure of the meeting allows for extensive scientific exchange between the researchers and intense discussions on the different research topics. Every day covers a specific theme in the field of brain imaging and discusses aspects ranging from theoretical concepts, methodology, experimental designs and clinical applications. Two internationally renowned scientists are invited for each dayto give keynote lectures on the specific topic. These lectures are followed by short communications from selected abstracts of younger researchers. Two extensive poster sessions with around 80 posters allow the younger researchers (mostly PhD students) to present their work to the colleagues and discuss it with the senior scientists. These discussions allow the younger researchers to get useful new contacts for their future career. The topics of ABIM 2022 include consciousness, language development, social neuroscience and theory-of-mind, emotion processing and stress and resilience. The 9 keynote speakers comefrom USA, Australia, UK, Germany, France and Italy. Five speakers are women, four are men.",,2022,Département des neurosciences fondamentales Faculté de Médecine Université de Genève,13489.53,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2021 +P27925,216737,Scholars at Risk Application_Ukraine_Dr. Olena V. Cherniavska _EXTENSION (Prof. Stefano Brusoni),"The idea that innovation and change are happening faster than ever has become a truism. In fact, the challenge is identifying those few things that -seemingly- are not changing at the same pace. This proposal builds on the observation that our teaching methods are indeed lagging behind the needs of students and educators alike. The COVID-19 pandemic made this lag very transparent. This proposal will focus three work-packages that aim at assessing how higher education institutions as well as corporate education entities are adjusting to the new normal. It aims at understanding what the 'new normal' actually is, in terms of balancing digital and physical training methods, and how this balance impact educational outcomes. The extension is needed to deepen and broaden the project.",,2023,International Affairs Office of the President ETH Zurich,67420.6,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P27943,216758,"The China Dream and its Nightmares: Representations of Power in Contemporary China's Cultural Sphere, 2012-Present","This proposal is designed to form part of the current major research project on 'The China Dream and its Nightmares: Artists and Writers in the era of Xi Jinping (2012-present)' conducted by Professor Daria Berg, DPhil Oxford, and her team at the Chair of Chinese Culture and Society, University of St.Gallen, on Chinese art, media, literature and culture in collaboration with HSG-SGI St. Gallen Institute for Management in Asia, Singapore; Palacky University, Olomouc, Czechia; The Centre for Chinese Visual Arts, Birmingham City University, The Universities of Oxford, Cambridge, Durham, SOAS, University of London, UK; Male University, Male, Maldives, and the Centre for Genocide Studies, Dhaka University, Bangladesh.This research project investigates the production of visual arts, literature and vernacular culture under Xi Jinping. Since his rise to power in 2012, Xi has centralised China's political and military power to provide a sense of stability against a series of socio historical events in the 2000s. From the global financial crisis, to the Wenchuan earthquake, milk powder scandal, and to the protests in Tibet in 2008, an increasing uncertainty has spread in China and worldwide, aggravated further by the slowing down of China's economy. To overcome the challenging times and reinforce the CCP as the political and moral beacon, Xi has taken action by tapping into the fears and dreams of Chinese citizens.This research project will examine three Chinese dreams and nightmares that have characterised Xi's rule from 2012 to the present: first, the Chinese Dream, which has pervaded the public, private, and digital realms since 2012; second, the Belt and Road Initiative (BRI), which has demonstrated China's desire to play a more central role globally since 2013; and third, the cultural impact of the recent outbreak of Covid-19, which has tested the authority of the CCP.While the scope of Xi's leadership has puzzled scholars in international studies, geopolitics, economics and area studies, its artistic, literary and cultural dimensions still await detailed investigation. This research project aims to redress this shortfall by exploring perceptions of the Chinese Dream, BRI, and Covid-19 pandemic in the visual arts, literature, and vernacular culture. Through visual analysis, conversations with artists, literature review and digital methods, this project provides alternative interpretations of the current power-dynamics and responds to the urgency to grasp the socio-historical changes in China today.",,2024,Universität St.Gallen Forschungsförderung,67277.4,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2023 +P27944,212433,"The China Dream and its Nightmares: Representations of Power in Contemporary China's Cultural Sphere, 2012-Present","This proposal is designed to form part of the current major research project on 'The China Dream and its Nightmares: Artists and Writers in the era of Xi Jinping (2012-present)' conducted by Professor Daria Berg, DPhil Oxford, and her team at the Chair of Chinese Culture and Society, University of St.Gallen, on Chinese art, media, literature and culture in collaboration with HSG-SGI St. Gallen Institute for Management in Asia, Singapore; Palacky University, Olomouc, Czechia; The Centre for Chinese Visual Arts, Birmingham City University, The Universities of Oxford, Cambridge, Durham, SOAS, University of London, UK; Male University, Male, Maldives, and the Centre for Genocide Studies, Dhaka University, Bangladesh.This research project investigates the production of visual arts, literature and vernacular culture under Xi Jinping. Since his rise to power in 2012, Xi has centralised China's political and military power to provide a sense of stability against a series of socio historical events in the 2000s. From the global financial crisis, to the Wenchuan earthquake, milk powder scandal, and to the protests in Tibet in 2008, an increasing uncertainty has spread in China and worldwide, aggravated further by the slowing down of China's economy. To overcome the challenging times and reinforce the CCP as the political and moral beacon, Xi has taken action by tapping into the fears and dreams of Chinese citizens.This research project will examine three Chinese dreams and nightmares that have characterised Xi's rule from 2012 to the present: first, the Chinese Dream, which has pervaded the public, private, and digital realms since 2012; second, the Belt and Road Initiative (BRI), which has demonstrated China's desire to play a more central role globally since 2013; and third, the cultural impact of the recent outbreak of Covid-19, which has tested the authority of the CCP.While the scope of Xi's leadership has puzzled scholars in international studies, geopolitics, economics and area studies, its artistic, literary and cultural dimensions still await detailed investigation. This research project aims to redress this shortfall by exploring perceptions of the Chinese Dream, BRI, and Covid-19 pandemic in the visual arts, literature, and vernacular culture. Through visual analysis, conversations with artists, literature review and digital methods, this project provides alternative interpretations of the current power-dynamics and responds to the urgency to grasp the socio-historical changes in China today.",,2023,Universität St.Gallen Forschungsförderung,114652.47,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2022 +P27947,208580,Longitudinal tracking of B cell and functional antibody responses to SARS-CoV-2 and other human coronaviruses in Africa,"Background and Rationale: In contrast to soaring COVID-19 case numbers during pandemic waves in the Americas and Europe, large parts of Africa have reported relatively low numbers of SARS-CoV-2 infections and COVID-19-related deaths. Hypotheses to explain this observation include differential innate and adaptive immune mechanisms of protection in different populations. Cross-protective immunity from prior exposure to endemic coronaviruses (HCoVs) and ""trained"" immunity from other pathogen exposures in Africa are suspected, but data are limited. Much has been learnt about immune responses to SARS-CoV-2 in U.S. and European COVID-19 patients, contributing to the development of effective vaccines. Similar studies in African populations with different immunological backgrounds are urgently required to define shared and distinct, potentially beneficial features of immune responses to SARS-CoV-2 and to investigate the nature and longevity of infection- and vaccine-induced immunity.Goal and Specific Objectives: The goal of this project is to characterize immune responses of rural and urban populations in Ghana to SARS-CoV-2 and HCoVs, and to COVID-19 vaccination. Results will be compared to available data from U.S. COVID-19 patients and vaccinees. Specific objectives are (i) to determine the point prevalence and longitudinal development of serum and saliva antibodies to SARS-CoV-2 and HCoVs in individuals from rural and urban areas, (ii) to conduct a detailed analysis of antibody specificities and effector functions in serum and saliva from study participants who had been infected with SARS-CoV-2, and/or HCoVs, and/or received COVID-19 vaccines, (iii) to analyze clonal B cell lineages in study participants to identify specific characteristics of class switching, immunoglobulin heavy (IGH) chain gene segment usage, and IGH complementarity-determining region-3 length and somatic hypermutation, and (iv) to develop monoclonal antibody (mAb)-based point of care (POC) tools to identify SARS-CoV-2 variant and HCoV infections.Methods: Study participants will be enrolled in rural and urban Ghana with longitudinal blood, saliva, and nasopharyngeal swab collection. We will use enzyme-linked immunosorbent-, Luminex-, and cell-based assays to examine functional properties of antibodies and high-throughput sequencing of B cell receptor (BCR) rearrangements combined with computational analysis pipelines to study clonal B cell lineages. Mouse and human mAbs will be generated using hybridoma technology and antigen-specific single B cell sorting.Expected Results: Results will shed light on SARS-CoV-2 and HCoV infection prevalence in rural and urban Ghana and give insights into the effects of HCoV immunity on the susceptibility of populations to SARS-CoV-2. Analysis of functional humoral and mucosal antibody responses and BCR repertoires will reveal characteristics of African immune responses and improve understanding of the potential interplay of local and systemic antibody-mediated immunity. SARS-CoV-2 variant- and HCoV-specific POC assays will provide tools for epidemiological studies on the prevalence and types of coronavirus infections.Impact: Comparative study of pre-existing and SARS-CoV-2 infection-elicited functional antibody responses and BCR repertoire features in Ghanaian versus other populations have the potential to reveal correlates of protection that may help explain differences in the impact of the COVID-19 pandemic on different continents. Analysis of antibody and B cell responses to COVID-19 vaccination will provide valuable information on characteristics and potential impairments of vaccine-elicited immunity in rural versus urban populations to inform public health action.",,2027,Clinical Immunology Dep. of Medical Parasitology and Infection Swiss Tropical and Public Health Institute,1521833.99,Human Populations,Black,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2023 +P27963,206813,Evolutionary trajectories of SARS-CoV-2 variants under immune selection,"The emergence of SARS-CoV-2, the etiological agent of Covid-19, in late 2019, causing a to-date ongoing pandemic, is one of the foremost global health crises of the 21st century. The pandemic has claimed millions of lives and is a major source of morbidity and mortality, as well as a major burden on the global economy. In an unprecedented effort, multiple highly effective vaccines have been developed, tested and administered to hundreds of millions of people. The vaccinations have greatly contributed to the protection of highly vulnerable patient populations. In late 2020, we observed the evolution of multiple variants that have demonstrated worrying phenotypes, including the B1.1.7/Alpha and B.1.617.2/Delta variants. These variants have been proven to be more transmissible than the initial strain introduced into the population and show, among others, multiple mutations in the receptor-binding domain of the viral spike protein. The receptor-binding domain of the viral spike is also the target of potent, neutralizing antibodies elicited by vaccination or natural infection. This has sparked fear, that these variants may represent vaccine escape variants. Although some of the variants demonstrate escape from certain classes of neutralizing antibodies, the vaccines still offer broad, albeit reduced, protection from infection, hospitalization and death. Evolutionary theory predicts that adaptation to novel environments is often governed by few mutations with large effects. The observation of increased transmissibility of e.g., the B.1.1.7/Alpha and B.1.617.2/Delta variants is likely to be the result of adaptations to the human ACE-2 receptor. In the light of widespread administration of vaccine and natural infection-induced immunity, it is unclear how immune selection will shape the evolutionary trajectories of the SARS-CoV-2 variants. We hypothesize that SARS-CoV-2 variants may escape neutralizing polyclonal immune responses elicited by vaccination. Furthermore, we hypothesize that SARS-CoV-2 is not able to independently optimize transmissibility and immune evasion and that escape variants based on highly transmissible strains will demonstrate lower transmissibility. We aim to address the hypotheses with the following objectives: In Objective 1 we will select SARS-CoV-2 escape variants using serum from mice immunized with an inactivated, whole virion SARS-CoV-2 vaccine based on an early variant (SARS-CoV-2/human/USA/WA-CDC-WA1/2020), currently under development in the Taubenberger lab. We will select escape variants starting from SARS-CoV-2/human/USA/WA-CDC-WA1/2020, the B1.1.7/Alpha and B.1.617.2/Delta variants, which demonstrate clear differences in their transmissibility. We will select the escape variants by serially passaging the variants in increasing serum concentrations and identify mutations by whole genome sequencing.In Objective 2 and Objective 3 we will assess the plaque-purified escape variants for two different readouts of transmissibility. We will measure growth kinetics by competing the cognate wild-type ancestor with the escape mutants and we will measure infectivity of escape variants using a focus-forming assay. Variants predicted to be less transmissible should demonstrate lower growth rates and reduced capability to form foci.In Objective 4 we will assess the IC50 of the serum from vaccinated mice against the escape variants and we expect an inverse correlation between readouts of transmissibility and the IC50 value.Combined, these results will grant us insights into aspects of the evolutionary trajectories of SARS-CoV-2 variants of concern under immune selection. We will learn if SARS-CoV-2 variants can independently optimize affinity for the human ACE2 receptor and mediate immune escape, knowledge of paramount importance to judge the further development of the pandemic. Such results will ultimately hint towards the necessity of updating the SARS-CoV-2 vaccine and might inform further vaccine development.",,2023,"Viral Pathogenesis and Evolution Section Laboratory of Infectious Diseases NIAID, National Institutes of Health",93033.47,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P27967,196732,How immune responses shape the clinical characteristics of COVID-19: a prospective cohort study in patients and their household contacts,"Background: On March 11th 2020, COVID-19 was declared a pandemic. Despite drastic measures to limit dissemination, it has already lead to a substantial death toll and enormous impact on health-care systems and the world economy. As data are emerging on the clinical manifestations caused by Severe Acute Respiratory Syndrome (SARS)-Coronavirus (CoV)-2, it is critical to understand its immunopathology and put it in perspective of previous SARS epidemics. The immunopathology of SARS disease is poorly understood because of the relatively limited access to patients and because animal studies do not reflect the complexity of human disease. Today, immunological and data analysis tools have progressed enormously and numerous accessible patients exhibit none to critical symptoms, enabling rapid and extensive characterization of SARS-CoV-2 immunopathology. Within 2 weeks of the outbreak of COVID-19 in Geneva, we established a clinical platform recruiting infected patients and used our expertise in clinical research in vaccines, infectious diseases and SARS-specific immunology to start addressing critical questions about COVID-19. In this unique position, we will collect samples before the onset of symptoms, through the monitoring and sampling of household contacts of infected patients, until convalescence. This will establish what constitutes protective or detrimental immune responses to SARS-CoV-2, critical open questions for the development of the numerous vaccines currently in the pipeline. A clinical study has been initiated in the Geneva University Hospitals, planning to include 50 patients (with no, mild, moderate, severe or critical symptoms) and 200 household contacts. All will be followed at regular intervals for clinical evaluation and harvesting of biological samples. We will perform a detailed longitudinal characterization of their immune responses before and after symptom onset.Objectives: 1.Assess the circulating and local innate response induced by SARS-CoV-2 prior to and after the onset of symptoms to determine which specific inflammatory markers (cell types, gene expression, cytokines) are associated with disease outcome. 2.Assess the SARS-CoV-2 specific adaptive responses during the course of COVID-19, which may influence disease outcome through clearance of virus or viral-infected cells and/or enhancement of innate responses.3.Define whether cross-reactive, non-neutralizing antibodies (or memory B cells) to other CoVs may play a role in enhancing disease by skewing the response of macrophages to SARS-CoV-2. 4.Establish prognostic or predictive markers of disease severity by performing a multi-parametric, unsupervised analysis of all parameters (clinical, immunological, viral). Experimental approaches: Innate cell phenotyping by flow cytometry, measure of a broad spectrum of cytokines in plasma and other biological samples, changes in blood gene expression analyses, serological assays and characterization of SARS-CoV-2-specific and cross-reactive B and T cell responses. Expected outcomes: Capturing asymptomatic subjects through the follow-up of household contacts of COVID-19 patients will define ""protective"" responses (innate and/or linked to rapid generation of SARS-CoV-2-specific immunity); this project will identify the potential role of prior exposure to other coronaviruses as well as protective or detrimental immune responses to SARS-CoV-2, supporting the complex development of COVID-19 vaccines (inducing protective response, avoiding disease enhancement) and immunomodulatory therapies.",,2022,Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève,307027.28,Human Populations,Unspecified,Not Applicable,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +P27974,206639,Characteristics and outcomes of patients with pneumococcal meningitis in the light of different vaccination policies and Covid measures,"Background and rationale: Streptococcus pneumoniae is the most prevalent pathogen causing bacterial meningitis. Invasive pneumococcal disease (IPD) includes PM, which has distinct epidemiological and pathophysiological characteristics compared to sepsis or pneumonia. PM leads to death in 15% and to long-term sequalae in one third of survivors. Vaccines cover up to 23 of over 100 pneumococcal serotypes. Vaccination policies differ between countries, e.g., the Netherlands and Switzerland, and serotype replacement has begun to counterbalance the initial decrease of IPD incidence observed after introduction of paediatric pneumococcal conjugate vaccines (PCV). Implementation of Covid measures has reduced the incidence of communicable diseases, including IPD. How these different developments affect patient characteristics and outcomes is unclear.Overall objectives: To evaluate the long-term effect of differing pneumococcal vaccination policies and Covid measures on patient characteristics and outcomes of PM.Specific aims: 1) To review European vaccination programs and vaccination coverage on PM and assess correlations with patient characteristics and outcomes. 2) To evaluate if patient characteristics and outcomes in Switzerland and the Netherlands, which have differing vaccination policies, vary. 3) To evaluate if patient characteristics and outcomes in the two countries changed before, during and after Covid measures.Methods: 1) European pneumococcal vaccination programs will be reviewed systematically and analysed for correlation with characteristics and outcomes of patients with PM.2) Data from the Swiss and Dutch mandatory surveillance and the Dutch nation-wide cohort study on bacterial meningitis will be searched for adults with PM. ?2-test will be used to identify differences in patient characteristics and outcomes between the Dutch and Swiss cohort.3) To compare incidence before, during, and after Covid measures based on the Oxford stringency index, we will estimate incidence rate ratios. Differences in serotypes and patient characteristics and outcomes will be tested using a ?2-test.Expected results: We expect that differing vaccination policies and Covid measures significantly affect patient characteristics and outcomes.Impact: Knowledge on the changing epidemiology of PM will influence policy making in terms of surveillance and vaccination strategies.",,2024,Department of Neurology Amsterdam Neuroscience Amsterdam UMC,142316.12,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Netherlands,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Indirect health impacts,2022 +P27978,193475,The Effect of Immune Imprinting: Epitope-level Analyses of Antibody Responses to Influenza Immunization Using Phage Display,"Background: Each year influenza viruses cause widespread infections during the winter months in the northern and southern hemisphere. Although existing antiviral drugs can shorten the duration of disease and reduce the risk of complications, disease prevention by vaccination is still the best option to reduce the burden of disease. Annual vaccination against seasonal influenza is recommended for individuals at risk, i.e. people above 65 years of age, pregnant women, immunocompromised patients and health care workers. However, vaccine effectiveness is low, usually only between 40-60%, depending on the antigenic match between the vaccine and the circulating influenza virus strains of a given year, on the health status of the patient and on the exposure history of each individual. The first strains encountered during childhood can cause immune imprinting, leading to skewed subsequent immune responses towards antigenic structures that are closely related to the imprinting strain. First reports that link the exposure history of patients to vaccine effectiveness date back to the 1940s and 50s. However, epitope-level analyses of antibody repertoires of individual patients that could identify imprinting strains and determine the individual exposure history have been hampered by a lack of appropriate methods. Existing methods include enzyme-linked immunosorbent assays (ELISA) using recombinant hemagglutinin (HA) proteins as antigens, hemagglutination inhibition assay (HAI) or microneutralisation assay (MN). However, these methods either have a low specificity due to the high cross reactivity of HA proteins (ELISA) or are not suitable to simultaneously detect antibodies against hundreds of influenza virus strains (HAI, MN). New serological methods are urgently needed to gain a more comprehensive picture of the exposure history of patients.Methods: In a pilot phase, we have adopted the phage immunoprecipitation sequencing (PhIP-Seq) technology to determine the humoral immune response after influenza vaccination to thousands of linear peptides derived from the HA protein of H3N2 strains. In this study, we will study the effect of different imprinting virus strains on the humoral immune response after vaccination in healthy adults and immunocompromised patients (ICP).Significance: The effect of exposure history and immune imprinting on vaccine effectiveness and susceptibility to influenza virus infections has been increasingly recognized in the past years. This will be the first study to determine exposure history and the imprinting virus strain through sophisticated state-of-the-art serological methods. These results will help to devise new vaccination strategies and identify immunity gaps, particularly for immunocompromised patients, which take the individual exposure history of individuals into account. This information will leave us better prepared for seasonal and pandemic influenza outbreaks will help to adapt public health measures, and decrease the burden of disease.",,2025,Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève,1173638.19,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Unspecified,Orthomyxoviridae,H3,,,H3N2,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Diagnostics | Immunity | Characterisation of vaccine-induced immunity,2021 +P27979,198299,Covid-Norms: Monitoring and Analyzing Preventive Behavior,"Background: Reducing the reproduction factor by infection prevention is the only way to combat Covid-19 until a vaccination becomes available. This may be reached by high levels of (personal) hygiene and social distancing as well as the fast interruption of infection chains by testing and contact tracing (Salathé et al., 2020). However, epidemiological simulations demonstrate that these measures only become effective if a crucial share of the population complies with them (Ferretti et al., 2020; Fraser et al., 2004). Among other factors, this resulted in an enforced lockdown of public life all over the world. Given the economic and social downsides of this enforcement as well as the increasing opposition and protests, alternative approaches need to be developed. Particularly in democracies that build on individual freedom and self-reliant decisions of their citizens, the only legitimate (and thus feasible) strategy is to convince the population to comply voluntarily with infection prevention. Hence, the challenge for combating Covid-19 in the long run will be to establish social norms that socially regulate compliance with protective measures in Switzerland by indicating what is and what ought to be done.Aims: Against this background, the present project aims to develop and support a normative approach to disease prevention. This requires 1) a profound theoretical and empirical understanding of the factors and dynamics of social norms of preventive behaviour regarding Covid-19 and 2) the translation of these scientific insights into evidence-based, concrete guidance for monitoring and influencing norms of preventive behaviour in the Swiss population.Model: The theoretical model for a normative approach distinguishes between collective norms (i.e. prevailing attitudes and behaviours in the population), mediated norms (i.e. the representation of these collective norms in news and social media) and perceived norms (i.e. perceptions of individuals about others' attitudes and behaviours). Based on the current state of research, we can assume that collective norms influence perceived norms directly through social learning (H1) and indirectly through their representation in media content (H2) and thereby induced media effects (H3). Furthermore, individuals adapt their behaviours and attitudes to their normative perceptions (H4), representing in aggregate collective norms. This process of norm development is recursive, and each step includes some biases and additional influencing factors, which is why norms are not stable but constantly evolving.Methods and data analysis: The project is designed to gain empirical insights into the dynamics of behavioural norms regarding social distancing, the use of the digital tracing app, and wearing face masks. According to health authorities (personal communication FOPH), these measures will be the most important protective strategies for a long-term containment of the coronavirus in Switzerland. Nevertheless, our methodological setup is flexible enough to adapt to other measures or the introduction of a vaccine. In order to empirically investigate the dynamics of social norms regarding these measures, we apply a longitudinal multi-method design. To cover all relevant influencing factors (e.g. risk perception, perceived efficacy, psychological traits, SES) and the short-term development on the individual level of perceived norms, attitudes and behaviours, we combine a cross-sectional survey (N = 1,500) with a daily mobile experience sampling over four weeks (N = 200). The long-term development of norms on the population level will be investigated over the course of 17 months (Aug 2020 - Dec 2021) by combining a weekly trend-survey (N = 29,750; 425 per week) with a large-scale, semi-automated content analysis of news media and social media that captures mediated norms. Longitudinal data analysis approaches (i.e. multilevel analysis, latent growth models and time-series analysis) will be used to gain differentiated insights into the causal, short- and long-term relationships between collective, mediated and perceived norms.Transfer and expected impact: The project builds on a close collaboration with the Swiss Federal Office of Public Health (FOPH). This collaboration is crucial regarding the project's aim to rapidly translate the scientific insights into evidence-based, concrete guidance for disease prevention during the Covid-19 crises. The weekly updated monitor of collective, mediated and perceived norms will inform ongoing communication strategies of the FOPH, such as the tracing app campaign, and will help to prepare a potential vaccination campaign. In addition to this contribution to combat Covid-19, we will elaborate in two workshops how to translate the findings into an effective normative approach to disease prevention for future public health challenges.",,2023,Institut für Kommunikationswissenschaft und Medienforschung (IKMZ) Universität Zürich,560557.67,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication,2020 +P27990,198412,Large-scale serological profiling of SARS-CoV-2 and related human CoVs with high-throughput microfluidic nano-immunoassays,"During the current SARS-CoV-2 pandemic, it became increasingly clear that there is a lack of diagnostic innovation in the field of emerging viruses. New, sophisticated, high-throughput technologies are urgently needed, such as reliable and accurate immuno-assays that can measure previous exposure to SARS-CoV-2 in thousands of samples in parallel. Such assays could be used to: i) determine the seroprevalence in the general population and in high-risk groups such as health care workers, ii) estimate existing risk factors or identify risk groups for contracting COVID-19, and iii) monitor population-immunity after natural infection or after vaccination, once a vaccine is administered to large parts of the population. We recently developed an entire suite of microfluidic nano-immunoassay devices, including a device capable of analyzing 1,024 serum samples in parallel with limits of detection (LOD) similar or better than standard ELISAs. This method requires only minute amounts of reagents leading to a cost per assay of a fraction of a cent and assuring reagent supply. We propose to apply this technology to serve as a serological profiling assay to detect IgG antibodies against SARS-CoV-2 and other circulating human-pathogenic CoVs for epidemiological sero-monitoring.",,2023,Laboratoire de caractérisation du réseau biologique - Institut de Bioingénierie EPFL STI IBI-STI LBNC,1070847.66,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P27995,200298,"Structure, dynamics and function of CCR5-arrestin interactions","The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in general inflammatory processes by recruiting and activating leukocytes. CCR5 is also the principal HIV coreceptor, is involved in the pathology of both cancer and neuroinflammation, and has been im plicated in the inflammatory complications of COVID-19. Binding of ligands to GPCRs results in the activation of G protein-, arrestin-mediated and other signaling pathways. The Grzesiek lab has recently solved the cryo-EM structure of an agonist chemokine CCL5•CCR5•G protein complex, which delineates the G protein activation pathway triggered by chemokine agonists within CCR5. While meanwhile a number GPCR•G protein complexes have been solved, much less is known on the structural basis of GPCR arrestin signaling. In particular, no structure of a chemokine receptor•arrestin complex exists. The Shukla is one of the world leading labs in the structural and functional analysis of arrestins.We propose here to combine the expertises and capabilities of these two groups to (A) solve the structure of a CCR5•ß arrestin 1 complex, (B) investigate the dynamics of interactions between CCR5-derived peptides and arrestin by NMR and other biophysical techniques, as well as (C) characterize the CCR5•ß arrestin 1 interactions by cell-based assays and develop new synthetic antibody fragments to stabilize the CCR5•ß arrestin 1 complex. The structural and functional insights from these combined experiments should decipher key elements of chemokine-induced CCR5-arrestin signaling and reveal differences to the G protein signaling pathway. This may pave the way for the development of directed therapeutics targeting either pathway. Due to the homology of CCR5 to a number of other chemokine receptors, the results obtained may serve as a paradigm for other chemokine receptor/ligand systems.",,2024,Abteilung Strukturbiologie und Biophysik Biozentrum Universität Basel,272993.02,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2021 +P28004,196544,"Incidence, Spectrum of Symptoms and Risk Factors for Coronavirus Disease 2019 (COVID-19) among Healthcare Workers - a Prospective Cohort Study","The Coronavirus Disease 2019 (COVID-19) pandemic - caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - has got significant implications on our daily life, currently dominating the medical agenda of the majority of health-care workers (HCWs). Case fatality rates vary significantly between studies, being alarmingly high in some of those, which probably reflects differences in the susceptibility of affected populations, but also in methods of surveillance, including testing frequency. HCW are at the center of this epidemic, both as care providers to severely-ill patients but also as potentially vulnerable population to acquire the infection due to heavy daily exposure to the virus. The burden of COVID-19 among the HCW population remains largely unknown, although single reports of fatalities have raised concerns among HCW regarding their own safety while caring for COVID-19 patients. In this study, we aim to prospectively assess the incidence of COVID-19, the spectrum of symptoms (including the proportion of oligo- and asymptomatic cases) as well as risk factors for infection among different types of HCW. For this protocol, we define HCW as hospital employees. We will include HCWs from an adult and a pediatric acute care hospital, and HCWs with and without patient contact. Main outcome in these study subjects is COVID-19 seroconversion. Dried blood spots will be collected bi-weekly to document seroconversion during a 4-month observation period; respiratory samples will be taken from symptomatic and non-symptomatic individuals. Data on risk behavior - including adherence to and use of personal protective equipment (PPE) - and on exposures in the hospital and the community will be gathered via an online platform; a daily text message will be sent out asking participants about symptoms compatible with a viral infection. Also, institutional factors such as number of hospitalized COVID-19 patients and availability of PPE will be monitored during the study period. The planned 1000 subjects were fully registered six days after the launch of the study promotion on March 19th and the full baseline sample collection will be completed within 10 days. We expect these findings to help better estimate the burden of SARS-CoV-2 and to better understand risk factors leading to (severe) infection among HCWs. We hypothesize that a significant proportion of seroconverted HCWs does not exhibit any symptoms. Differences in adherence to general hygiene principles, different exposures as well as personal risk factors might explain differences in susceptibility and severity of the disease.",,2021,Infektiologie und Spitalhygiene Departement Innere Medizin Kantonsspital St. Gallen,403556.57,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures,2020 +P28007,201694,The neighborhood in the cloud: How on- and offline location-based social networks shape individual life chances,"Neighbors matter and the ongoing COVID-19 pandemic highlights this truth quite drastically: Neighborhoods are important sources of help and support in times of crisis. But neighborhoods also have an enduring effect in normal times. From educational attainment and job market integration to political participation or the everyday help elderly people receive (e.g., Bayer, Ross, and Topa,2008; McClurg, 2006; Nieuwenhuis and Hooimeijer, 2016; Seifert and König, 2019): Neighborhoods, localized social networks, and other geographic contexts shape individual behavior by offering opportunities and imposing restrictions. Although the family and school context are often taken into account when examining educational outcomes (e.g., Hedman, Manley, and van Ham, 2019;Wodtke and Parbst, 2017), the role of other social networks (e.g., professional networks formed at one's working place) has so far been largely neglected in the study of neighborhood effects (Petrovic, Manley, and van Ham, 2019; Van Kempen and Wissink, 2014). More importantly, the role of localized online social networks is completely absent in the literature on neighborhood effects. At the same time, the stunning increase in neighborhood help initiatives during the COVID-19 pandemic has highlighted not only the importance of such localized networks but also demonstrated that they are increasingly organized online (Neue Zürcher Zeitung, 2020).The aims of this project are twofold: On the one hand, it assesses the simultaneous effects of multiple, often overlapping contexts and networks on people's educational and labor market chances, political participation, and everyday support. This allows us to put neighborhood and other contextual effects into a broader perspective. On the other hand, as the first of its kind, the project assesses how localized social networks (i.e., among neighbors) also manifest in online networks and interactions. Can such location-based online communities provide support and resources that have previously mainly been accessible through face-to-face interactions? The internationally unique project will provide us with a comprehensive picture on how different on- and offline location-based networks shape life chances and inequalities in different spatial entities.To rigorously test how localized on- and offline networks shape individual life chances and inequalities, new sources of data are needed. This is why a unique longitudinal survey will be set up to evaluate people's neighborhood, work, and friendship networks. Using modified position generators, the survey will also assess to which extent place-based networks manifest themselves online across different geographic contexts. To model the interactions in small-scale, bespoke neighborhoods of door-to-door neighbors, participants are chosen by means of a stratified cluster random sampling (Zangger, 2019a). Moreover, choice experiments and factorial surveys allow for the causal investigation of the underlying social mechanisms. Although the survey yields information on people's use of location-based online networks, the extent of such networks and how information and resources diffuse therein is evaluated using web scraped data from public Twitter and Facebook posts and groups in Switzerland (Russell and Klassen, 2018). This approach will yield data that complement the insights on place-based online interactions obtained from the survey and provide first insights on how neighborhoods ``in the cloud'' also shape attitudes, decisions, and inequalities.Combining traditional survey research with innovative methods, including modified survey experiments and big data approaches, the project will provide a comprehensive picture of neighborhood effects on people's life chances. Simultaneously assessing the influence of different, often overlapping contexts and networks (e.g., friends, at one's workplace), the project is unique in its direct assessment of the underlying social mechanisms of neighborhood effects and provides first intuitions on the role of location-based online interactions. Moreover, since data are collected in different geographic contexts, the project also broadens the narrow focus of existing neighborhood effects studies that focus on urban areas. The potential and relevance of the project become even more apparent against the background of the multifold spontaneous neighborhood help initiatives during the COVID-19 pandemic, which were partly organized online. The project will make internationally valuable and unique contributions for the study of context-dependent individual life chances and inequalities. This knowledge and understanding could not have been more timely, relevant, and useful and will provide invaluable insights for location-based policy interventions.",,2026,Institut für Soziologie Universität Bern,1157728.37,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P28036,196059,How to protect healthcare workforce during an epidemic outbreak: Modelling a desynchronization strategy from the COVID-19 pandemic,"During worldwide pandemics, protecting caregivers and thereby maintaining the medical workforce is a crucial and challenging task. Under such extraordinary situations, the sustainability of the healthcare providers is threatened by several factors including: 1) infected patients, 2) infected co-workers and 3) the infected community. Unlike most other professions, social distancing is extremely difficult in medical teams where healthcare workers are required to work in close contact with patients and colleagues. Currently, little is known about which work organizational strategy in hospitals is most suitable to protect the healthcare workforce. Therefore, the current project aims to identify if organizational measures installed during the COVID-19 outbreak were effective in protecting caregivers. This is of high relevance as during the course of an epidemic the healthcare workforce may become a scarce resource during later phases of the epidemic.The proposed project is designed to analyze data from the current COVID-19 outbreak to understand how organizational approaches may protect the healthcare workforce in a large university hospital. The obtained data will be used for the simulation and refinement of mathematical modelling to develop strategies that can be adapted for new regions affected by this, recurrent and future epidemic outbreaks. Aim 1. Determine the difference in risks of infection between healthcare and non-healthcare workers in a hospital environment The design of the study allows to determine the different roles on infection of hospital employees being 1) patient contact 2) no patient contact, working place in the hospital 3) home office. The model will determine to what extent these different roles impact of infection rates of workers and patients.Aim 2.Determine the impact of early testing on healthcare personnelAn intensive strategy of testing twice weekly for SARS-CoV-2 was established locally in one clinical unit. By assessing health status and productivity of the workforce compared to other departments allows to determine the relevance of frequent testing of asymptomatic healthcare workers for the protection of workers and patients. Aim 3.Determine the effectiveness of a desynchronization strategy to protect healthcare workersA desynchronization strategy was installed in one large unit in which the entire staff was dichotomized. Each of the two teams is working alternating for one week with the goal to reduce contact between the teams and decrease infection rates of the workforce. By comparing health status and productivity of the workforce to other departments will determine the relevance of such organizational distancing in healthcare workers. With the empirical data collected in Aims 1, 2 and 3, mathematical models will be developed, tested and simulated for impact evaluation. Modelling approaches address parametric as well as stochastic effects and extend the existing models that were developed for larger populations. Furthermore, the studies are designed to measure and model the productivity of the workforce resulting from the different organizational strategies. SignificanceWithin this project, the consequence of the COVID-19 outbreak on the workforce of a large university hospital will be analyzed and used to design new models for new regions affected, recurrent and future epidemic outbreaks. The results of this project will help to define the best strategy to organize the healthcare workforce of a hospital. The final goal is to be able to care for both infected and non-infected patients, while minimizing the risk to staff a thus maintaining a healthy caregiver workforce. Given the fact that data are available for many non-healthcare workers the results will also be modeled for non-healthcare institution. Therefore, these studies allow to determine the relevance of home office and desynchronization strategies to protect workers in their environment during and epidemic outbreak.",,2022,Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital,305019.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Infection prevention and control | Health Systems Research,Impact/ effectiveness of control measures | IPC in health care settings | Health workforce,2020 +P28069,211836,"16th World Congress of Bioethics: ""Bioethics post Covid-19: Responsibility and transparency in a globalized and interconnected world""","The World Congress of Bioethics (WCB) is the largest gathering of thought leaders in the field of bioethics. The academic conference takes place every two years, alternating in location between a high and low/middle income country (the past four WCBs were held in Philadelphia, USA; Bengaluru, India; Edinburgh, Scotland; and Mexico City, Mexico). As the only global conference in the field of bioethics, the WCB aims at facilitating interdisciplinary and cross-national discussion of cutting-edge issues in bioethics, and showcasing agenda-setting perspectives for the bioethics community. Hence, this event is the perfect opportunity for participants to engage with the most current developments in bioethics from a cutting-edge community of experts. The WCB 2022 therefore provides a leading platform to discuss important questions of social and scientific value and the role that bioethics can and should have for our society and future generations. This will be accomplished through a broad range of activities, both in-person and virtual, such as: a cutting edge scientific program exploring emerging issues in bioethics, public health ethics, global health, responsibility in scientific advancements and many more. With the participation of esteemed keynote speakers and panel experts; networking activities for both in-person and virtual participants, the Congress aims to facilitate exchange of information and ideas among the global bioethics community. Further, the WCB 2022 will ensure that early career participants gain the opportunity to engage with bioethics and enhance their skills to thrive in the academic environment.""Bioethics post Covid-19: Responsibility and transparency in a globalized and interconnected world"" is the topic that the WCB 2022 will focus on. The WCB 2022 is a ""Hybrid"" meeting. It includes (1) LIVE Plenary Sessions: 3 hours of Plenary sessions with Keynotes and Panels that will be live-streamed during each day of the congress. This Plenary session will be a common event that every Congress participant (virtual and in person) will follow together. (2) In-Person participation in Basel: Our Congress participants who will join us in-person Basel will have the opportunity to present their contributions during the days of the conference. Thus, they will experience a ""normal"" congress that we know of prior to the pandemic. Furthermore, parallel sessions taking place in Basel will be streamed via Zoom (like a webinar) to accommodate those virtual participants who wish to attend certain sessions. (3) All Virtual participants will also have the opportunity to present their talks during the days of the conference as virtual parallel sessions.We have put together an exciting list of key experts who will be part of the 3-Hours of Live Keynotes and Panel Discussions on topics ranging from inclusive bioethics, COVID-19, and Bioethics Leadership. Our experts are diverse since we have sought to have a balance of both male and female scholars, as well as scholars from different continents. This diversity is important in our ever interconnected world.The 16th WCB taking place between 20 - 22nd of July 2022 was awarded to the Institute of Biomedical Ethics, Universtiy of Basel after a competitive vetting process by the International Association of Bioethics (IAB). The Congress occurs under the aegis of this association. The WCB will be of great value for Swiss research. First, the congress will assist in elevating the Institute for Biomedical Ethics at the University of Basel, to become one of the main centers of bioethical investigation on a European and global scale. Second, it will support making Switzerland the cradle of the global discourse in bioethics for 2022 and beyond. Third, having the congress taking place in Basel, will facilitate Swiss scholars in participating to the event, thus promoting the dissemination of their novel research and allowing them to network with a cutting-edge community of experts from all over the world.",,2022,Institut für Bio- und Medizinethik (IBMB) Universität Basel,15699.4,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2022 +P28072,209953,The COVID-19 pandemic and its implications for urban essential workers,"The COVID-19 pandemic has radically affected people all over the globe, yet its impact has been unequal depending on the resources and opportunities people have to protect themselves and to cope with the multiple consequences of the pandemic (National COVID-19 Task Force 2020). These inequalities have been exacerbated in cities, especially with regard to urban labour issues (Wade 2020). Only some workers could work from home, while others had to step out and up, becoming what we call now 'essential'. Essential workers help the rest of us keep a semblance of normality and reduce our risk of infections (Kabeer et al. 2021, The Lancet 2020, Grever 2022), while risking their health, and in many cases not receiving the most basic health and safety measures themselves (McNicholas and Poydock 2020).While the first image of essential workers that might come to mind is that of healthcare personnel, most of those composing essential labour are made up of low-wage service workers (Kabeer et al. 2021), working in jobs related to care and maintenance (Bhattacharya 2017, Coss-Corzo 2021). People performing these jobs are infrastructural to the functioning of our societies, and they range from day care personnel to bus drivers and waste collectors. Intersectional burdens, expressed in the overlapping of race, class, and gender, have been reproduced in the pandemic (National COVID-19 Task Force 2020, Ho & Maddrell 2021), as care and maintenance work has fallen disproportionately on the shoulders of women (Bahn et al. 2020), people of color (Holder et al. 2021), and migrants (The Lancet, 2020).We propose a multimethod and interdisciplinary research project that connects qualitative and quantitative social science methods and that is informed by public policy, urban studies, and labour studies. We will retrospectively examine the situation of non-healthcare urban essential workers (such as public transportation drivers, day care personnel, urban cleaning workers, and delivery workers) during the pandemic in the five biggest Swiss cities. This focus allows us to examine not only their often precarious working conditions, but also the mismatch between their received policy support and their provision of key labour at the frontline. Given their 'essentiality' but low valuation, it becomes fundamental to understand their experiences, needs, and demands as a basis for developing more effective policies to support them. Furthermore, we will study how Swiss decision-makers and the wider population perceive and valuate these workers and policies in support of them, and how these valuations contrast with the lived experiences of urban essential workers. Four research questions guide our project:1)What are the experiences and struggles of non-healthcare urban essential workers during the pandemic and their corresponding policy support demands?2)How do those experiences, struggles, and policy support demands differ between diverse types of non-healthcare urban essential workers? (see Table 2 for a typology)3)How do decision-makers assess the need for policy support for different types of non-healthcare urban essential workers?4)How are policy support measures for different types of non-healthcare urban essential workers accepted by the population?",,2026,"Spatial Development and Urban Policy IRL, D-BAUG ETH Zurich",412527.25,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2023 +P28084,196440,Translating Anti-Coronavirus Virucidal Compounds,"The current coronavirus (COVID-19) pandemic has highlighted the world's need for effective antivirals. These drugs have to be ready at the start of the pandemic so to stop (best case scenario) or, at least, to slow down the contagion by decreasing the average number of infected people by a single sick patient. We need drugs to buy time for vaccine development. It should be obvious that, for a drug to be ready even before a new virus emerges, it has to be a broad-spectrum one. The PI and co-PI have been working for years to develop such drugs. It is known that the vast majority of respiratory (and sexually transmitted) viruses have attachment ligands that share a common target. They either attach to heparan sulfate proteoglycans (HSPG) or sialic acid (SA). Many compounds that imitate HSPG or SA have been developed over the years. Most of them have shown broad-spectrum activity in vitro and very low toxicity (the paramount example would be heparin). None has been translated into a drug. The key stumbling block lies in the mechanism itself. The virus binds to these compounds (and not to the cell surface) and hence is blocked in its cell-entry process. Binding, though, is a reversible event and, upon dilution (an inevitable event in vivo), the compounds-virus complex disassociates leaving an infective virus to replicate and re-start the infection process. A few years ago, the PI discovered that these compounds can be modified so that, upon binding to the viruses, they exert a local interaction capable of irreversibly damaging the virus. The result is an irreversible interaction because the virus can never regain its infectivity. Two classes of materials have been developed, one capable of mimicking HSPG and the other mimicking SA. In both cases results from ex vivo (on human respiratory tissues) and in vivo (in mice) experiments confirm the efficacy of the compounds. Direct comparison between comparable 'reversible' and 'irreversible' molecules show the superiority of the latter ones in tissues and animals. The key compounds in each of these classes are modified cyclodextrins. Cyclodextrins were chosen because they are naturally occurring sugars commonly used in commercial deodorants or as FDA approved Active Pharmaceutical Ingredients. The scope of this project is that of accelerating substantially the process of taking these molecules towards FDA approval. In order to do this, we propose to (work package 1, WP1) perform glycan arrays and in-depth in vitro study to clarify the interaction mechanism and determine the ideal molecule to inhibit SARS-CoV-2. At the same time, we will (WP2) perform in-depth studies to render the synthesis of the two cyclodextrins compatible with Good Manufacturing Practices (GMP) and render them ready for scale-up production. We will also study (WP3) the stability of the molecules in various storage conditions. Finally, emphasis will be placed in preparing a drug that is not only valuable against SARS-CoV-2 but that has a strong probability to work against the next coronavirus outbreak. In that sense, there will be an effort (WP4) to find conserved targets across the three coronaviruses that have affected humanity in the last twenty years (SARS-CoV, MERS-CoV, and SARS-CoV-2). In this sense, the potential use of a mixture of two or three compounds will be investigated.This project will provide the fundamental science support to other efforts that have been undertaken in the PIs laboratories (pharmacokinetics and toxicity studies, in vivo efficacy studies) that are aimed at rapidly taking these two molecules in Phase I clinical trials. Finally, both the PI and the co-PI are part of Sinergia project in whose framework these molecules were developed. That project is studying the basics of the mechanism of irreversible viral inhibition. This project is complemental to that one as it is designed to lower one of the barriers that exist between the development of an effective molecule and its testing in humans.",,2022,Supramolecular Nano-Materials and Interfaces Laboratory EPFL - STI - IMX - SUNMIL,270241.66,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +P28085,206554,"Living in a chronically ill body: Mapping women's embodied experiences with long covid (Oxford, UK)","Background. Long covid is a chronic illness in which the symptoms of the COVID-19 coronavirus continue over long time periods. It affects one in five COVID-19 patients. Researchers have framed it a 'silent epidemic' due to its complex health consequences, and the lack of data and follow-up on patients suffering from the disease. Recent studies have found that long covid particularly affects women (Sudre et al., 2020) and according to some studies, up to 60-70 % of the patients are female (Turabian, 2019). Female patients' symptoms are often being dismissed or attributed to anxiety or other psychological origin, also known as the 'gender pain gap' (Cleghorn, 2021; Kolmes & Boerstler, 2020). Data for race and ethnicity of the pandemic and its consequences are also lacking, which hinders documenting health inequities (Krieger et al., 2021). Medical and epidemiological research has sought to understand patients' symptoms, which include brain fog, fatigue, depression, shortness of breath, headaches, cough, fever, and insomnia. These studies are crucial for understanding the broader implications of long covid on the population as a whole and guide policy and clinical interventions. However, more information is needed on the ways that women as the most affected group with diverse backgrounds experience their (ill)health and the ways they respond to their health condition. Objectives and aims. 1) How do women experience long covid and how do these experiences differ depending e.g. on age, race, ethnicity, sexuality or education? 2) In what ways are these experiences related to multimorbidities such as stress, mental health problems, changes in quality of life or capacity to work? 3) How have the women adjusted to their new way of life and how has this changed the way they view themselves?Concepts. The project is situated within health humanities, which help to understand the ways that diseases affect our everyday lives beyond physical health, specifically 1) health geographies, which analyse how health is constituted through the social and cultural environment, how individuals experience ill-health and diseases, and how those different experiences are shaped by power and knowledge (Brown et al., 2018; Dyck et al., 2012), 2) gendered and intersectional perspectives on health arguing that women and men experience illnesses differently (Hankivsky, 2012) and considering the differences of women's experiences depending on intersectional identities (Brown et al., 2019; Browne et al., 2008); and 3) translating health knowledge as an approach to translate experiences with (ill)health and include patients' and clinicians' experiences into health research (Engebretsen et al., 2017; Greenhalgh et al., 2019).Methods. This project draws on 1) interviews with patients and health professionals (n=20) for a broader understanding of the research context (Elwood & Martin, 2000) and 2) body mapping (Gastaldo, 2012; Jokela-Pansini, 2021) (8 workshops, 8 participants per workshop, n=64) as a visual research method. I apply qualitative content analysis (Elo & Kyngäs, 2008; Hsieh & Shannon, 2005) to analyse the data. I use a participatory approach (De Leeuw et al., 2012; Pain, 2004). I have consulted patients on the research design and will engage participants in data collection and -analysis. Results and impact. Understanding the effects of long covid on different bodies and population groups has become ever more important. Studying long covid is particularly interesting in UK where more than a million people are living with long covid (ONS, 2021). The body mapping method, combined with interviews, will reveal new information on how women map and narrate their experiences with long covid. Resulting in concrete visualisations - life-sized drawings of women's bodies - the project will raise awareness of the illness to a broader public through an exhibition combined with discussions with patients and different stakeholders. With its interdisciplinary perspective and collaboration with scholars in human geography and medicine as well as participatory methods, the project will formulate joint recommendations for responding to long covid that consider women's diverse backgrounds.",,2024,School of Geography and the Environment University of Oxford,132721.76,Human Populations,Unspecified,Unspecified,Unspecified,Women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Gender,,,United Kingdom,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P28086,222164,Women living with long covid: a participatory approach to study access to healthcare services and support (UK and Switzerland),"""",,2025,Unit Labour Geography Institute of Geography University of Zurich,132303.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Health Systems Research",Community engagement | Health service delivery,2024 +P28093,198321,An optimized prophylactic mRNA vaccine against coronavirus disease 2019,"Background and rationale: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights that mRNA vaccines are the fastest formulation to manufacture: the company that I co-founded in 1999, CureVac (Tuebingen, Germany), as well as two other large mRNA companies (BioNTech, Mainz, Germany, founded in 2008, and ModeRNA, Boston, USA, founded in 2008) are at the front line and have already begun human clinical studies with mRNA vaccines coding for SARS-CoV-2 proteins. A non-replicating mRNA-based format was used for our first mRNA-based anti-cancer vaccine subject to clinical studies (first patient injected in 2003 in Tuebingen) and is currently in use against coronavirus disease 2019 (COVID-19). Non-replicating mRNAs are very safe vectors that are easily and quickly produced. However, the doses required to obtain a good antibody response after intra-dermal or intra-muscular injection are relatively high and in the range of 100 micrograms per injection. Accordingly, the phase I study by ModeRNA involved two intra-muscular injections administered 28 days apart with doses of 25, 100 or 250 micrograms for both vaccinations. Based on the phase I results, the company is now doing a phase II study with two doses: 50 and 100 micrograms. Should a 100 microgram dose be required for the final vaccine, vaccinating the population of Switzerland twice would require 20 million doses, which corresponds to two kilograms of purified mRNA, i.e., at least 400 litres of transcription reaction. This cannot be achieved easily and quickly, even when conducted by a large industry such as Lonza, because the raw materials (cap analogues, nucleotides and polymerases) are not readily available in such large amounts. Accordingly, among the four different mRNA vaccines that BioNTech is testing in large phase I studies in association with Pfizer, one is self-amplifying mRNA that requires much lower amounts of material than non-replicating mRNA.Overall objective and specific aims: We aim to generate an optimal mRNA vaccine for sub-cutaneous, intra-muscular or intranasal administration that induces a strong antibody response with amounts of mRNA one thousand-fold lower than the amounts of mRNA required for the non-replicating mRNA vaccines currently being tested.Methods to be used: Replicating mRNAs are efficacious in triggering immune responses at doses 400-fold lower than those of non-replicating mRNAs. The production of five grams of mRNA is feasible (covering two injections of 10 millions people). Thus, a replicating format is best adapted to a world pandemic in which billions of vaccine doses would be required. A novel, safe, efficacious and cost-effective version of replicative mRNA could take the form of a two-component vaccine consisting of a non-replicating mRNA coding the replicase (that can be stored and used in any vaccine) and a replicating mRNA coding the antigen (to be produced according to the virus that generates the pandemic): the transreplicon. This technology was recently reported (Beisser et al. Mol Ther. 2020 Jan 8;28(1):119-128) and shown to be equivalent to a non-replicating mRNA vaccine with a dose at least 400-fold lower: in mice, intra-dermal injection of 50 ng of the transreplicon coding for influenza HA gave an antibody response and neutralizing titres similar to those of the intra-dermal injection of 20 micrograms of non-replicating mRNA coding for influenza HA. The purpose of the present grant is to implement this trans-amplifying mRNA vaccine and to optimize its formulation for sub-cutaneous, intra-muscular or intranasal vaccination. We will optimize this technology using our expertise (sequence of the antigen, of the replicase, structures of mRNAs, ratios of replicative and non-replicative mRNAs) and formulate the two mRNAs in nanoparticles (in our proprietary protamine nanoparticles as well as commercially available or innovative liposomal particles). These will be characterized and evaluated in vitro. We will then measure anti-SARS-CoV-2 Spike protein antibody and neutralizing titres induced after sub-cutaneous, intra-muscular or intranasal administration of the selected formulations in mice. As benchmark positive controls, we will use the intra-dermal injection of naked trans-amplifying mRNAs, as described in Beisser et al., and the intravenous injection of our usual spleen-targeted liposomal non-replicating mRNA formulation.Expected results and their impact: We expect to identify a nanoparticle formulation of a trans-amplifying mRNA vaccine that will induce a strong antibody response with the sub-cutaneous, intra-muscular or intranasal administration of transreplicon in the range of one nanogram per mouse. The outcome will be a safe, efficacious, versatile and inexpensive mRNA vaccine against coronavirus that can also be the basis for easily and quickly manufactured vaccines against any new viral threats.",,2022,Dermatologische Klinik Universitätsspital Zürich,294384.39,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2020 +P28096,217588,18th congress of the international society of travel medicine (CISTM18),"After several years of COVID-19 impacting on the ability to meet face-to-face, the forthcoming 18th congress will enable the International Society for Travel Medicine to meet in Basel from May 21-25, 2023 in Basel. Personal contacts are pivotal for scientific exchange, for developing novel research ideas together with an international audience. The Swiss Tropical and Public Health Institute (Swiss TPH), which has recently expanded into a sustainable four story headquarter building in Allschwil on the outskirts of Basel, will host the congress at the Basel Messe.The Scientific Program Committee has built a program that addresses many of the contemporary issues in travel medicine and migrant health which will trigger the long awaited personal exchange in participative discussions. There will be state-of-the art lectures, prominent speakers, workshops and debates, ample opportunities to discuss controversies in travel medicine, as well as free oral communications on latest research findings.As the chair of the Local Organizing Committee (LOC), Christoph Hatz will ensure as the scientific coordinator at the Swiss TPH that participants of CISTM18 will engage closely among themselves and promote scientific exchange in the fields of migration and travel medicine. The last two years have been extremely challenging as the global COVID-19 pandemic has greatly disrupted international travel including migration and medicine in tropical countries, and has resulted in many of medicine practices being substantially curtailed and even temporarily suspended. The theme ""Dawn of a New Era in Travel Medicine"" provides many stimuli to the international audience which will cross-fertilize the Swiss participants. Some of the program highlights include plenary and symposia on the impact of COVID-19 and climate change on travel, antimicrobial resistance, tick-borne diseases, migrant health, and the rising threat of artemisinin treatment failures for malaria-infected travelers. Introductory sessions for novel travel medicine providers as well as others on highly specialized topics such as migrant health, a focus on leishmaniasis, human trafficking, and dengue are further topics. The congress offers an excellent opportunity for Swiss scientists and physicians to learn and exchange scientific developments and new venues of research in the respective fields.The official scientific program will start on May, 21st 2023 at 13.00h and end on May, 25th 2023 at 13.30h, thus five congress days. Following the official congress program (from 15-18h, at the Swiss TPH in Allschwil), an international, three-hour symposium will be conducted by the Swiss Specialist Society for Tropical and Travel Medicine together with the Swiss TPH and guests from the respective partner countries Tanzania, Peru, Thailand and India to foster the international scientific exchange between Swiss physicians and scientists together with established partners from the South..",,2023,Swiss Tropical and Public Health Institute Medical Service Unit,24546.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2023 +P28104,210122,Contentious Non-Compliance with Pandemic Response,"During the COVID-19 pandemic, social conflicts have emerged that are directly related to the compliance with pandemic measures. In addition to some enforced restrictions, the Swiss pandemic strategy heavily relied on voluntary compliance and appealed to personal responsibility. In this context, we will focus on the points at which this strategy was met with political resistance and dynamised social conflicts. The research subject is the politically motivated rejection of COVID-19 containment measures and the conscious refusal to comply with them in everyday life. We are analysing this rejection of pandemic measures with the innovative concept of 'Contentious Non-Compliance' (CNC). In our definition, it comprises participation in protests against the pandemic regime or forms of intentional everyday disobedience-such as refusing to wear masks or to be vac-cinated. Most often, however, the two forms occur alongside each other. This novel concept combines the study of non-compliance with pandemic measures with a movement-study perspective.The project is centred on the following questions: What forms of politically motivated non-compliance have occurred in Switzerland and how can CNC be explained in Switzerland when compared to other Western European countries? Although protests against COVID-19 containment measures have also occurred in other European countries, in most places the individual protests did not turn into fully-fledged episodes of contention, i.e. more permanent non-compliance protests as in the German-speaking D-A-CH countries. A similar picture emerges within Switzerland, where regional differences with regard to CNC became apparent. To understand the peculiar pattern in the development of CNC protests in Switzerland, we pursue an international and interregional comparative design. We use the comparative method to analyse seven Western European countries with the aim of discerning patterns of socio-structural, cultural and institutional features that are associated with heightened protest intensities. Then, by means of a process analysis, the changing political opportunity structures for CNC are being elaborated in the selected countries. These findings are then transferred and further substantiated by ethnographic in-depth research into articulations of CNC in Switzerland. The concept of political opportunity structures allows for an in-depth understanding of various elements complicit in the emergence of contentious politics, and thus-in our case-for an analysis of non-compliance as a social conflict. Hence, we focus on non-compliance as a 'collective political struggle' that emerged in the context of the disruptively enforced implementation of new behavioural norms in the form of pandemic measures.In summary, three research fields are of particular relevance for the proposed project: Research on non-compliance, research on structural and institutional preconditions of different pandemic responses and protest research on the Corona protests. The planned research project responds to research gaps in all three fields and combines them into an innovative programme that, for the first time, brings the fields of social science research on the pandemic into dialogue with protest studies approaches. In the field of non-compliance research, the distinction between different roots of non-compliance allows us to shed light on the social and political components of non-participation in pandemic measures and to support concrete pandemic strategies. In the area of the preconditions of different pandemic responses, the international and interregional comparative design enables the investigation of the structural dimensions that have led to different forms of contention in different countries and regions. This makes the complex constellation of institutional, socio-structural and cultural preconditions for the development of CNC empirically tangible. This offers new points of reference for protest research, which is also enriched by the investigation of more everyday practices of contention that became visible outside the protests and presumably perpetuate forms of non-compliance in the rest of the population. Therefore, social science pandemic research is also enriched; for, we argue that it is precisely the level of political movements that is crucial to understand public assessment, longer-term acceptance and, ultimately, the effectiveness of pandemic measures, which remain partly dependent on voluntaristic compliance. In close cooperation with our project partners at the Federal Office of Public Health, we pursue three interrelated objectives: Firstly, we want to provide substantial insights into structural prerequisites and processual elements of CNC protests. The project develops a refined understanding of the cultural, institutional and socio-structural preconditions of CNC through an international and interregional comparative approach. Process analysis is of use in designating specific interaction dynamics in the evolution of the non-compliance protests. Secondly, we want to develop an in-depth account of CNC and its everyday aspects in Switzerland. By means of different qualitative methods, we enrich the concept of CNC by its life-world articulations and offer perspectives on different protest milieus. Thirdly, we want to synthesise these findings to obtain practically relevant and application-oriented knowledge on CNC during the pandemic in Switzerland. The focus on CNC is, however, not only useful for ongoing pandemic events but also for institutional strategies in situations of disaster or crisis, as well as for other large-scale institutional interventions in social behaviour as they might become necessary in the combat against climate change.",,2026,Institut für Soziologie Universität Basel,534606.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2023 +P28112,220624,Development of a human-based cell-free translation screening to identify SARS-CoV-2 Nsp1 inhibitors,"The COVID-19 pandemic has resulted in significant public health and economic impacts worldwide, highlighting the urgent need for effective therapies to combat the virus. Developing a high-throughput screening platform to identify potential SARS-CoV-2 Nsp1 inhibitors represents a pioneer strategy that can significantly impact public health and basic research.SARS-CoV-2, like other coronaviruses, inhibits host cell translation, promoting viral protein synthesis and dampening innate immune responses. Nsp1, a viral protein expressed in Alpha- and Beta- coronaviruses, plays a critical role in this process, making it an attractive target for drug discovery. Several potential candidate molecules have been identified through in silico searches, but their ability to restore translation in the presence of Nsp1 is unknown. However, identifying Nsp1 inhibitors has been challenging due to the lack of effective screening platforms based on translation inhibition. Traditional high-throughput screening assays based on living cells can be costly and non-specific, making them less effective for identifying potential inhibitors. In contrast, cell-free (in vitro) translation allows the monitoring of protein synthesis using cell extracts with reporter mRNAs, bypassing possible cytotoxic effects. However, the increased costs, limiting amounts, and the non-reproducible features of human translation-competent lysates have prohibited so far the development of human in vitro translation-based high-throughput screening assays.To overcome this limitation, the proposed project aims to develop the first cell-free high-throughput screening based on human mRNA translation to identify potential inhibitors of SARS-CoV-2 Nsp1. A key point for the feasibility of the project is that I previously established a cutting-edge cell lysis method based on dual centrifugation that enables the application of specific mechanical forces during lysis. This innovative method yields ample amounts of translation-competent lysates optimized over the past few years, making it ideal for high-throughput screening. The assay will use in vitro transcribed, capped, and polyadenylated reporter mRNAs encoding for Renilla luciferase, a widely used reporter protein in cell-free translation assays. The assay can function in a minimal scale of 5 µl reactions in 384-well plates, producing reliable and reproducible luciferase signals. A high z?-factor value of 0.881 has been achieved under the final experimental conditions, indicating the assay's high quality.The screening will be performed at an academic screening facility with cutting-edge equipment and vast experience setting up high-throughput screening assays. It will include a pilot screen phase in duplicates for 1280 compounds and dose-response curves (DRCs) for ten compounds in duplicates for ten concentrations. The primary screen will be designed in duplicates for 30'000 compounds, followed by verification of inhibition with reporter mRNA at a single concentration for 300 hit compounds in duplicates. Potential inhibitors will be further characterized in vivo in their capacity to inhibit Nsp1 expressed in human cells. Additionally, several assays will be performed to provide important information concerning the toxicity, distribution, metabolism, and excretion properties as well as the physicochemical and pharmacokinetic behaviour of the selected hits.The potential impact of this project is immense. Identifying Nsp1 inhibitors can lead to the development of novel therapeutic targets and improve the therapeutic or preventive potential against Betacoronaviruses like SARS-CoV-2 and MERS-CoV. Moreover, the success of this approach could pave the way for the development of similar high-throughput screening assays for mRNA translation-related processes, opening up new avenues for drug discovery and improving our ability to combat infectious diseases.The proposed project is not only highly unconventional but also has the potential to impact the field of virology and public health significantly. In addition, the project has several technical innovations that add to its promise of success as it will provide an indispensable and highly versatile tool for basic and clinical research in mRNA translation. Its completion in an academic setting increases the social value of the project as it will allow open access to potential therapeutic reagents.",,2024,"Department of Chemistry, Biochemistry and Pharmaceutical Sciences University of Bern",117238.82,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2024 +P28114,203310,Human and Algorithms for Detecting and Counter-attacking Fake Medical News,"Recently, an abundance of false or misleading medical information has been observed on the Web and particularly on social media, posing a considerable threat to public health while eroding trust in healthcare systems. 6 out of 10 people search for the cause of their medical condition online, and among those who found a diagnosis online, 35% does not visit a professional medical provider. The COVID-19 pandemic has exacerbated this problem by bringing forward an infodemic surrounding the coronavirus that spreads as quickly and deadly as the virus itself. As of Aug-2020, at least 800 people may have died while about 6000 people are hospitalized because of COVID-19-related misinformation. Excerpts taken out of context from the Swissmedic report regarding the PCR test have been shared and reshared in several Facebook posts leading to public distrust in the effectiveness of the test. Fake news involving alternative COVID-19 treatments have led people in Vietnam stocking on hydroxychloroquine depriving in-need patients of access to their life-saving drugs. Such incidents demonstrate the need for a novel framework to combat fake medical news that can not only detect them early and accurately using algorithmic models but also counter-attack their claims by leveraging human experts.While research on fake news has recently attracted considerable attention, research on fake medical news is still in its infancy, but it proves to be a formidable challenge. First, fake medical news poses the same challenge as general fake news as social networks with their open nature are perfect breeding grounds for fake news to be produced and propagated at an alarming rate. Second, fake medical news is more personal and highly opinionated, as it is directly connected to people's wellness. As a result, early detection is paramount in preventing the potential damage of fake medical news, as in some cases, it could be a matter of life and death. Third, in comparison with social or political fake news, fake medical news is not geographically-dependent, i.e., the same fake medical news can ""infect"" different populations having different socio-cultural backgrounds. This requires techniques to handle fake medical news to be multilingual. Fourth, fake medical news is usually a misinterpretation (either unintentional or malicious) of claims from scientific papers or scientists. Therefore, techniques to detect fake medical news need to be able to discern and deduce correct claims from misinterpretations.Existing techniques for detecting fake medical news in online social networks focus on building fully autonomous machine learning models. While these models excel at processing large amounts of data in a short time, they often require a huge amount of training data, and they lack a deep understanding of medical contexts. This prohibits them from detecting unseen emerging fake medical news. Human experts, on the other hand, can recognize new patterns but lack the ability to handle large amounts of data. An approach that handles this trade-off is to leverage algorithmic models for fast detection while using human experts for validating algorithmic detections and identifying unseen fake medical news. In this project, we form a positive feedback loop between human experts and algorithmic models where models assist humans in keeping up with large data while humans help models in identifying emerging fake medical news.This project aims to build a human-powered real-time system for detecting and counter-attacking fake medical news from large-scale dynamic social networks with multi-lingual, scalable, and cost-effective techniques. The system constantly monitors thousands of information diffusion channels and issues alarms on suspicious information waves. Human experts are employed to validate these emerging medical news, assisting algorithmic models to train themselves to become smarter and adaptive to unseen patterns of fake medical news. The specific aims of this project are:1) Construct a graph-based detection model capturing relationships among different actors by incorporating data from multiple sources;2) Build a seamless and cost-effective integration of human experts and algorithmic models in which the most suspicious emerging fake medical news is validated by human inputs;3) Design large-scale and dynamic protocols for timely warning of fake medical news, ensuring the system to work with high-volume and high-velocity data streams from social networks,4) Assemble a Web-based social network observatory to dispute fake medical claims and provide contextual information on fake medical news for users to disseminate, thereby, halting the spread of misinformation.This project is expected to have a significant scientific and real-world impact. From a scientific perspective, it designs and establishes a novel semi-automatic fake medical news detection model that smartly integrates human and machine. From a real-world perspective, the project results will be disseminated via various formats, including an online observatory dashboard that offers the general public not only facts and figures but also anecdotes and user stories to counter-attack claims in fake medical news. From an interdisciplinary standpoint, the research will have an immediate impact during the pandemic, while its long-lasting legacy would be in hundreds of domains that fake medical news has touched, such as political science, social science, and journalism.",,2024,Laboratoire de systèmes d'information répartis EPFL - IC - IIF - LSIR,195711.22,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2022 +P28116,198297,Unravelling consequences of SARS-CoV-2 mediated inflammatory immune responses in heart and vasculature,"The 2019 coronavirus disease pandemic (COVID-19) is a global public health challenge, with rapid spread, high reproductive rates, and an approximate mortality rate between 1.0-2.3%. Due to the lack of specific treatment, therapy has so far been limited to symptom relief. Although acute respiratory distress syndrome (ARDS) is the central feature of disease severity, non-pulmonary organ damage has emerged as an important predictor of mortality. Severe cases admitted to hospital for COVID-19 are significantly affected by cardiovascular disease (CVD) and kidney failure as well as symptoms of the central nervous system (CNS), all of which correlate with a poor outcome. However, the underlying mechanisms of non-pulmonary tissue damage in COVID-19 and associated coagulopathies are poorly understood. CoVasc combines the complementary expertise in vascular inflammation/atherosclerosis (Döring, Van der Vorst), neuroimmunology/brain barrier function (Engelhardt), coagulation/complement activation/thrombo-inflammation (Rieben, Sorvillo), heart development and function (Mercader), and electrophysiology and vascular coronary function of the heart (Odening, Longnus, Kleinbongard) with expertise in virology and specifically SARS-CoV-2 (Dijkman, Leib) and know how in BSL3 research (Leib, Summermatter), also with respect to animal models (Benarafa), to unravel the consequences of SARS-Cov-2 mediated inflammatory responses in the cardiovascular system. There is lack of certainty about which cell types are prone to be infected and how the route of infection or cell type being infected determines disease manifestation. One established entry point of SARS-CoV-2 into cells is angiotensin converting enzyme 2 (ACE2), expressed in several cell types including endothelial cells, pericytes and cardiomyocytes. Within CoVasc we propose to combine our complementary expertise in cardiovascular biology to study SARC-CoV-2 infection employing primary and iPSC-derived in vitro models of human microvascular and macrovascular endothelium, as well as pericytes and, in vivo in animal models, namely zebrafish and mouse. As CD147 was identified as an alternative ligand for SARS-CoV-2 and is highly expressed on the endothelial and epithelial brain barriers, it will also be included in our analysis. We will study if disease progression is dependent on the cell type infected and combined analysis of animal models will allow us to study long-term outcome of infection, which is currently completely unknown. Beyond providing the knowledge which vascular cell types can be infected by SARS-CoV-2 and the receptors involved, CoVasc holds the promise of providing insight into yet unknown downstream signaling events triggered by SARS-CoV-2 and involved in the observed coagulopathies or neurological symptoms. CoVasc may thus set the stage for characterization of COVID-19 clinical phenotypes, and, therefore, for discovering entirely novel avenues for therapeutic intervention targeting the vasculature and or the brain barriers for the treatment of COVID-19.",,2023,Universitätsklinik für Angiologie Departement Herz & Gefäße Inselspital und Universität Bern,2206648.16,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,Disease pathogenesis,2020 +P28122,196852,Defining the immune signatures in SARS-CoV-2 infected individuals in blood and tissues,"Background: To date (23rd of March 2020), 170 countries confirmed the presence of infected individuals on their territory, and more than 333'000 people have already been infected worldwide. The number of deaths related to SARS-Cov-2 virus approximate 14'000 individuals. In Switzerland, 8'060 people were infected, and 66 people already died. Every day, 50'000 individuals are infected worldwide with SARS-CoV-2 and about 5% of them develop severe acute respiratory syndrome and no predictive markers of such evolution are currently known (https://www.bag.admin.ch/). The fine characterization of the immune signatures associated with intensive care unit (ICU) and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally may help to improve the care of infected patients.Hypotheses: Severe SARS-CoV-2 infection is due to dysregulated immune responses that might be identified at the time of admission/diagnosis.Objectives: In this context, the proposed research project plans to 1) define specific ex vivo immune signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally ; 2) characterize the innate and adaptive CD4 and CD8 T-cell responses of ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally; 3) establish whether the specific immune signatures identified in Objectives 1-2 are associated with the clinical presentation of patients with SARS-CoV-2 infection; and 4) to characterize the organ distribution, morphology and immunopathological features of the tissue lesions in SARS-CoV-2 infected individuals succumbing to disease, and to correlate with immune signatures and responses described above.Experimental strategy: To address these objectives, we will assess the ex vivo cellular and serum immune signatures, the blood transcriptome and will define the SARS-CoV-2-specific CD4 and CD8 T cell profile of ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally, and perform ex vivo studies on biological fluids and tissue obtained from autopsies.Expected outcome: The proposed research project has the potential to substantially advance the delineation of immune dysregulation observed in SARS-CoV-2-infected individuals who underwent severe acute respiratory syndrome. In particular, the proposed research project will define the specific immune signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally.Significance of the research project: To date, SARS-CoV-2 infection remains largely poorly characterized. In this context, this research project has the potential to provide key information on the immunological signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis, which may help improve the care of infected patients and may help to guide the selection of a preventive vaccine. These results will improve the diagnosis and follow-up of affected patients. The strength of the proposed research project relies on the unique combination of the clinical expertise of the Division of Immunology and Allergy, the Service of Infectious Diseases and the Institute of Pathology of Lausanne University Hospital and the use of the most modern technologies to comprehensively characterize the immunological parameters associated with SARS-CoV-2 infection.",,2022,Division d'Immunologie et d'Allergie CHUV,308880.56,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +P28124,200839,Digital Transformation at the Local Tier of Government in Europe: Dynamics and Effects from a Cross-Countries and Over-Time Comparative Perspective (DIGILOG),"Digital transformation constitutes one of the most important innovations at the local level of government and is expected to reshape local service delivery, public administration, and governance in Europe fundamentally. Most recently, the COVID-19 pandemic has shown the fundamental importance of a well-prepared digital administration to replace analog processes, not only but most urgently needed in times of physical distancing (Kuhlmann et al., 2020a). In many countries, local government is the most significant tier of public service delivery, ensuring proximity to citizens and a key player of digital transformation (Steiner et al., 2018; Kuhlmann, 2009, p. 21; Bouckaert/Kuhlmann, 2016).Against this background, it is a matter of concern and criticism that in current comparative research concerning the digital transformation of state and administration, local levels of government have been insufficiently investigated. Indeed, there is no systematic, cross-countries comparative knowledge available regarding the state of implementation and the effects of digital transformation at local government level in Europe. This collaborative research project is intended to remedy those deficits. Its first main research questions address the dynamics, scale, and pace of digital transformation in European local government, i.e., to what extent there has been radical/rapid revolutionary or gradual/slow evolutionary change and how and why these dynamics differ when considered from a cross-countries and inter-municipal perspective. The second main research question addresses the (intended and unintended) effects of digitalization on local self-government in Europe in terms of outputs (service delivery, organization, processes, and human resources), outcomes (performance and accountability), and impacts (citizens' acceptance, governance, new cleavages). The independent variables include explanatory factors on the macro-level (institutional properties of the local government systems), meso-level (internal organizational arrangements and procedures), and micro-level (actor strategies, interests, motives).The project will generate coherent data for a systematic comparison using methodological triangulation, i.e., quantitative and qualitative methods. It will take the form of a regular and automated quantitative survey of all local authorities in 47 European countries (members of the Council of Europe), based on web crawling and machine learning techniques - this is a novel approach in the context of the social sciences - and qualitative research, namely case studies in selected European countries. Renowned scholars from the University of Potsdam, ZHAW, and the Vienna University of Economics and Business, with extensive experience in local government and comparative research, form the consortium of this project.Key deliverables of the project will be an openly accessible monitoring platform of digital transformation at the local tier of government, journal articles, an edited volume, and publications for practitioners. The real-time platform ""Monitoring Digital Transformation in European Local Governments"" is accessible to researchers and practitioners worldwide and contributes to a better understanding of long-term developments. The duration of the project being submitted to the SNSF/DFG is three years; however, by automating the process, the real-time platform will continue to exist and be updated regularly beyond this timeframe. The research project will yield policy-relevant knowledge concerning local digitalization measures from a European perspective, which can then be utilized to improve policymaking for future public sector modernization.",,2025,School of Management and Law ZHAW,665479.92,Human Populations,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P28143,220496,"Science, Expertise and other Modes of Knowledge: Trends, Patterns, and Prospects","The short history of the SARS-COV-2 virus has impressively displayed how scientific knowledge simultaneously co-constructs political and social worlds and, in turn, is shaped by these spheres. The virus overhauled our daily lives all over the globe and brought unprecedented challenges to conventional modes of governance and established regimes of scientific expertise.From an STS perspective, these challenges may not appear to be entirely novel in nature. However, in these times of crisis discourse on topics such as, for example, climate change, the loss of biodiversity, and energy supply, STS studies are attaining new societal relevance. STS approaches and concepts offer relevant analytical frameworks to analyse current trends, to unpack the social imprints of scientific knowledge production and to develop new options for action. At the same time, recent STS debates on the Covid-19 crisis have also displayed the limits of existing STS theories and concepts. Scholars have pointed to the need to develop new approaches that rethink, reflect, reshape, rehabilitate the place of knowledge in policy and society to imagine and pursue more sustainable futures.Against this background, the conference aims to address the questions of how diverse knowledge regimes shape social identity, political citizenship, and cultural heritage. How are knowledge claims fashioned, represented and questioned? What kind of features and mechanisms influence their success or defeat? How do current societal transformations influence different knowledge claims and their residues of non-knowledge, such as subjugated, lay, or amodern forms of knowledge? In short, we are particularly interested in the ways in which such modes of producing knowledge claims essentially shape our views and our relationship with the world around us.The STS-CH conference aims to bring together Swiss and international scholars from all career levels around current issues in science, policy and society. We are interested in exchanging research on the broad spectrum of STS topics and therefore welcome contributions by researchers working across various disciplines, research fields and communities of practice.",,2023,Kulturwissenschaft/Europäische Ethnologie Universität Basel,12222.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts | Other secondary impacts,2023 +P28153,198438,Short- and long-term neuropsychological impairment following COVID-19,"Initially characterized as a severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), new clinical observations in the acute phase of the infection suggest that COVID-19 is also frequently associated with neurological disorders. These observations are supported by recent cohort studies indicating the presence of such disorders in patients with severe COVID-19 infection, in some cases even before the usual respiratory symptoms appear. Mao et al. (2020) found that 36.4% of COVID-19 infected patients had neurological symptoms involving the central nervous system, peripheral nervous system, and skeletal muscles. Encephalopathy is the most common neurological manifestation observed during the acute phase among patients followed in intensive care, but stroke has also been observed. A direct role of the virus is suspected, but cumulative data indicate that an over-exuberant immune response to the virus, which can involve pro-inflammatory cytokines (cytokine storm syndrome), could explain both the acute respiratory disease syndrome and the encephalopathy. At the neuropsychological level, confusion, severe executive dysfunction, and major attention fluctuations are the most commonly reported features (Helms et al., 2020). Although neurological and neuropsychological hypotheses predict their presence, we do not yet know whether there are any short- or long-term neuropsychological sequelae to COVID-19. If there are, another critical question is whether these effects are only present in patients with the most severe forms followed in intensive care, or if they are also present in patients with far milder and even asymptomatic forms. Moreover, are these possible short- and long-term effects correlated with epidemiological risk factors such as age, sex, sociocultural level, body mass index, brain lesions, comorbidities, or the expected neuropsychiatric disease in the wake of this massive public health crisis? These questions are of critical importance regarding the clinical characterization of the virus in humans, and thus fully aligned with the priority areas of the RNP 78 SNSF call (Module 4). In this context, the objective of the COVID-COG project is to assess the possible short- and long-term neuropsychological consequences of COVID-19 at 3-6 months and 12 months after the infection. We will compare patients divided into three groups according to the gravity of the respiratory syndrome during the acute phase of the infection: 1) patients who were followed in intensive care; 2) patients who were hospitalized but did not require intensive care; and 3) patients who tested positive but did not require hospitalization. To this end, we will carry out a comprehensive neuropsychological assessment evaluating cognition, emotion and mood, as well as a brain MRI. Based on observations during the acute phase, we expect to observe executive and attentional disorders among patients without stroke. For patients with stroke, we expect to observe additional deficits, depending on the location of the lesion. The intensity of these deficits may be proportional to the severity of the symptoms during the acute phase, but this question remains totally open. The project will be supervised by Doctor Julie Péron and Professor Frédéric Assal. Dr Péron is Head Neuropsychologist at the Adult Neurology Department of University Hospitals of Geneva (HUG), and Director of the Clinical and Experimental Neuropsychology Laboratory at the Faculty of Psychology and Educational Sciences of Geneva University. Prof. Assal is Head Behavioural Neurologist at HUG's Adult Neurology Department, and Associate Professor of Neurology at Geneva University's Faculty of Medicine. The project will also involve six medical doctors involved in the acute-phase care of patients with COVID-19 and will be implemented at HUG, in order to secure a sufficient number of patients, as well as provision of the necessary skills and equipment.",,2023,FPSE Université de Genève,605599.2,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P28154,220041,Longitudinal evolution of cognitive functions following SARS-CoV-2 infection: factors of chronicization,"""",,2027,FPSE Université de Genève,793457.88,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Indirect health impacts,2023 +P28155,218870,Cycling through the pandemic. Tactical urbanism and cycling practices in the time of Covid19,"""'Cycling through the pandemic' provides insights on how the tactical urbanism has the capacity to influence change in mobility practices such as cycling. Covid-19 crisis prompted the public authorities to rethink the use of public space in order to develop means of transport that are both efficient and adapted to the health context. The book addresses these measures in Europe, North and South America through policies analysis, mapping, surveys and qualitative analysis. It analyses how those new infrastructures and policies can be a trigger for change in a context of mobility transition.""",,2023,Institut de géographie et durabilité Faculté des géosciences et de l'environnem. Université de Lausanne,15034.96,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28162,206732,Human genetic basis of natural resistance to SARS-CoV-2 infection,"Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. They mostly occur in otherwise asymptomatic patients in which PCR and serology failed to demonstrate SARS-CoV-2 infection. Our hypothesis is that genetic factors predispose these individuals to mount a robust innate immunity against the virus, making them resistant to the infection. The innate immune response is linked to a strong type I interferon (I-IFN) response, which clinically manifests as chilblains, promotes early viral clearance, avoiding the development of both disease and adaptive immunity. This hypothesis is based on 3 observations: (1) Chilblain patients had close contact with SARS-CoV-2 infected individuals before disease onset; (2) Despite exposure to the virus, they did not develop COVID-19 symptoms or adaptive immunity against the virus, suggesting resistance to infection; and (3) Chilblains are linked to a strong I-IFN activity, as demonstrated by the dominant lesional I-IFN expression signature. We will test our hypothesis by first measuring I-IFN responses in a cohort of SARS-CoV-2-associated chilblain patients. To assess the intrinsic functionality of their innate anti-viral immune system, we will stimulate peripheral blood mononuclear cells (PBMCs) with surrogates of viral nucleic acids. Because intrinsic functionality of the innate immune system is strongly controlled by genetic variation, we will search for monogenic inborn variations of I-IFN-mediated resistance by analyzing whole-exome sequencing (WES) data in large cohort of chilblain cases. We will recruit chilblain patients including family clusters at the international level through the global COVID Human Genetic Effort; search for candidate mediators of innate resistance using innovative strategies developed in the laboratory to analyze WES data; and perform extensive functional studies to understand the mechanisms through which they influence innate defenses against SARS-CoV-2.This project should unravel the ""COVID-toe"" enigma and identify correlates of protective innate immunity against SARS-CoV-2. It has the potential to identify previously unrecognized genes and pathways involved in innate immunity and drive the discovery of new targets to boost anti-viral responses.",,2024,Rockefeller University,129954.77,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United States of America,,Clinical characterisation and management,Disease pathogenesis,2022 +P28163,201817,Political Misinformation in the Digital Age,"Digital misinformation is threatening contemporary democracies. From Europe-wide no-mask protests of COVID-19 deniers to growing opposition to 5G antennas amid ungrounded fears of health risks, it is hard to downplay the detrimental consequences of political misinformation on the quality of democratic decision-making. What makes citizens vulnerable to political misinformation in the digital age? And how can we develop better corrective interventions to limit misinformation? Two challenges currently prevent us from addressing these questions: first, existing concepts, explanations, and corrective strategies tackle the production rather than the consumption of misinformation; second, established notions are swiftly losing grip over algorithmic-driven misinformation. DIGIMIS aims to overcome these challenges, changing how scholars and policy-makers think about misinformation in the digital era. To accomplish this, DIGIMIS will: 1) formulate and test an encompassing theoretical model accounting for heterogeneous cognitive vulnerabilities to political misinformation and related typical forms of misinformation consumption, 2) apply these new conceptual tools to investigate real misinformation networks and cascades, 3) identify how algorithmic decisions can shape the consumption of political (mis)information, 4) develop a new class of misinformation's corrective interventions targeting causal misperceptions. DIGIMIS relies on a comparative multi-method empirical design mixing traditional and computational social science methods, including smartphone-driven data collection with embedded experiments. DIGIMIS is groundbreaking in 1) developing innovative measures mapping misinformation and news literacy in the digital age, 2) pioneering innovative empirical strategies involving fine-grained behavioral data in an experimental setting, 3) developing next-generation correctives to limit misinformation effects.",,2026,Institute of Political Science University of Zurich,657214.08,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2022 +P28172,212988,Addressing Corporate Human Rights Impacts: the Responsible Stakeholder Model at the Intersection of Corporate Sustainability and Business and Human Rights,"Background, and rationaleIn the context of the ongoing global pandemic, the research visit will explore few anticompetitive practices of price control, drug availability and other monopoly privileges exercised by states and corporate holders of patents over vaccines and medicines for the prevention and treatment of Covid-19. While such monopoly privileges are underpinned by the shareholder primacy business model and will enhance higher returns on investment for shareholders, such predatory practices are how-ever at the expense of the rights to healthcare of corporate stakeholders in the Global South such as end users and consumers of these vaccines who will have to contend with either paying highly exorbitant prices for the patented vaccines or risk suffering the potentially severe or even fatal health impacts of Covid-19 due to non-availability or unaffordability. Accordingly, the research proposes Responsible Stakeholder Model (RSM) as a business model that will remain relevant in the wake of the on-going concerns especially for the Global South about equitable access, affordability, and sup-ply in sufficient quantities of any patented Covid-19 curative medicines or vaccines around the world. Against this backdrop, the proposed research uses a perspective at the intersection between BHR and corporate law, the research draws on, explores and further expands the frontiers of the RSM as already developed and compared with other business models in the corporate responsibility domain elsewhere. The theoretical assumptions and regulatory consequences of the RSM will be expanded and applied within the Business and Human Rights (BHR) discourse towards ensuring corporate-related human rights abuses are remedied if not prevented. To be precise, the RSM will be further interrogated within the contexts of the UNGPs together with more recent efforts in the BHR domain such as the EU mandatory corporate sustainability due diligence duty to address negative human rights and environmental impacts. Overall objectivesThis research visit has two overarching aims: First, it aims to explore the intersection between Com-panies Law and BHR towards creating a workable business model in newly codified directorial du-ties to adequately respect and fulfil corporate constituents' human rights. The model will seek to ensure corporations remain commercially competitive for investors, but also providing effective safeguards to stakeholders from the impacts of asocial exercise of corporate powers.Second, the research visit aims at establishing continued collaboration between scholars at the Insti-tute and the visiting researcher and his home institution. The proposed interdisciplinary research fits well and contributes to the collaborative aim of this research stay by linking the expertise and research focus - i.e., BHR - of Prof. Florian Wettstein at the Institute for Business Ethics, University of St. Gallen, and the aim and purpose of the Competence Center for African Research (CCAR) with the visiting researcher's comparative Companies Law and BHR backgrounds. Methodology The proposed research will embrace a comparative analysis/approach in its overarching research findings. Generally, comparative approach could either be 'legislative', when foreign laws are invoked in the process of drafting new national laws (legal transplantation process), or 'scientific' and 'theoretical', when the comparison of different systems or disciplines is undertaken simply to im-prove or expand knowledge. The research adopts the comparative analysis as a scientific tool to-wards expanding socio-legal knowledge within the Business and Human Rights (BHR) and the Corporate Law disciplines with a view to identifying, assessing and eliminating unnecessary but perceived differences in the disciplines and promoting the workable business model to fulfilling corporate constituents' human rights. Expected outcomesUpon completion of this research stay, the researcher expects to produce a collaborative research paper with Prof. Florian Wettstein. The focus of the research will be on the intersection of BHR and Companies law towards finding a workable business model addressing corporate-related human rights abuses and risks. The interdisciplinary research will benefit from the extensive experience and expertise of Prof. Wettstein in BHR which complements the researcher's background in comparative Companies law.ImpactThis research stay affords the opportunity, first, for mutually beneficial exchange of ideas to expand knowledge especially regarding the unnecessary compartmentalization of the BHR discourse and undue isolation of corporate law in creating an effective and sustainable remedial framework to ad-dressing business-related human rights impacts. Second, the discourse on the intersection between BHR and Companies law is still early stage among researchers on the African continent. This re-search stay provides a rare opportunity to meet with and collaborate with Professor Wettstein, a front-running expert on the discourse and expand legal knowledge on the subject in the researcher's affiliated universities, especially at the Centre for Comparative Law in Africa (CCLA), Faculty of Law, University of Cape Town, South Africa. Third, tapping into the proposed research's empirical focus on Africa and the researcher's affiliation with universities in Africa, the research visit opens an opportunity for continued collaboration with the Competence Center for African Research (CCAR) at the Institute for Business Ethics. Fourth, the research visit will provide the researcher with the opportunity to develop and deepen necessary research and related scholarly skills towards his career development.",,2022,Institut für Wirtschaftsethik (IWE) Universität St. Gallen,4664,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2022 +P28186,210066,Pandemic-resilient Space for Sustainable Cities - Urban Places for the Pandemic Resilience of young people.,"The justification for this project is based on a combination of the following aspects: •The significant impact of the COVID-19 pandemic on the lives of young people•The enormous importance of urban space for young people and how it has changed and intensified during the pandemic•The relationship between young people and urban space, being almost exclusively regarded as a problem There are some preliminary studies and recommendations for practice concerning the above-mentioned issues. However, they address young people exclusively from the perspective of professionals, whereby they are mostly questioned about their well-being. In our study, we take young people seriously as experts in both their recreational environment and their ideas and wishes for processes of its development. This transdisciplinary project puts them on an equal footing with the professionals in planning, development, and maintenance of urban space and with us as scientists. In doing so, the project equally pursues scientific (1, 2, 6) and practice-related (3, 4, 5) objectives that build on one another: 1.Understanding young people's actions and needs in and around urban space and the related2.understanding of the importance of urban space regarding young people's pandemic resilience. 3.By focusing on the importance of urban space for the pandemic resilience of young people, the discourse on the contribution of urban space to sustainable development and its pandemic-related design will be stimulated. 4.The direct involvement of young people should also provide insights into the participatory orientation of design processes and thus5.enables young people to experience self-efficacy in political processes. 6.The reflection of the research process will also contribute to the further development of participatory and transdisciplinary methods under crisis conditions.The project addresses these topics using qualitative methods of social research. It follows the paradigm of grounded theory in its further development as situations analysis. Creative methods are used to work with young people, and problem-centred interviews are conducted with professionals. Materials are evaluated qualitatively using content analysis. Human and nonhuman elements such as places and discourses were integrated in periodical situation analyses. An intersectional view of young people enables us to highlight multiple forms of pressure and needs for space. Based on these findings, recommendations for the design of urban places and for participatory development processes were derived. In addition, an interdisciplinary and international sounding board support the reflection of findings and methods. The research process is structured with a transdisciplinary workshop series including all the participants. The participation of young people in the entire research process promises deeper insights into the field of research than claimed by studies ""about young people"". The analysis of the evolution of the pandemic is likely to provide valuable information on the pandemic resilience of urban space, embedded in the requirements of sustainable urban development. Owing to the participation of professionals in the research process, the thus gained and co-produced knowledge directly addresses their challenges and can be instantly applied. The reflection on the methods applied should give advice regarding future-oriented action under crisis conditions for both science and practice.",,2026,Institut für Vielfalt und gesellschaftliche Teilhabe ZHAW Soziale Arbeit,435082.67,Human Populations,Unspecified,Adolescent (13 years to 17 years),Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2023 +P28188,198673,Enzymatic Construction of DNA-Encoded Chemical Libraries (EnzyDEL),"On March 11th, 2020 WHO Director-General Dr. Tedros Ghebreyesus declared the novel coronavirus (COVID-19) outbreak a global pandemic noting that the WHO is ""deeply concerned both by the alarming levels of spread and severity and by the alarming levels of inaction"". As of May 31st, not even three months later, the WHO reported close to 6 million confirmed COVID-19 cases worldwide with more than 350'000 deaths linked to the disease. Apart from the tragic human consequences of the COVID-19 pandemic, few countries will be left unscathed by the coronavirus outbreak's financial ramifications. The UN predicts that the slowdown in the global economy is likely to cost at least $8.5 trillion leading to a sharp increase in poverty and suffering. The discovery of active pharmaceutical ingredients is a time-consuming process. As a consequence, efforts to implement platforms and tools for the rapid identification and development of drugs against existing and novel disease-relevant targets are of highest priority. While neutralizing antibodies nowadays can be quickly generated, they so far fail for certain viral diseases due to the fast mutation rates of the respective viral coat proteins and additionally are difficult to administer to intracellular targets. This, in principle, could be better achieved with small molecules, however the generation of specific, high-affinity small molecules is a major pharmaceutical challenge.At present, the so-called DNA-encoded chemical library (DEL) technology is considered to be the most powerful method for the discovery of suitable small molecule high-affinity binders4. Building on the idea of Brenner and Lerner to transfer the biological concept of linking phenotype and genotype to the world of small molecules, David Liu (Harvard University) and Dario Neri/ Jörg Scheuermann (ETH Zurich) established the concept of using DNA barcodes to uniquely identify small molecules in large compound collections. In a single test tube, small molecule libraries of up to a billion members have been created and used in affinity-based selection identifying new drug leads.To further advance the powerful DEL technology, the here-proposed project targets to broaden the scope and quality of chemical transformations accessible on DNA by harnessing the catalytic power of enzymes. Enzymes, Nature's catalysts, function in aqueous media at ambient temperature and are highly specific and tolerant to a wide variety of functional moieties making them ideal tools to build-up molecular diversity in the presence of a DNA strand. Targeting the construction of the pharmaceutically highly relevant C-N bonds through the use of tailored cocktails of natural and engineered imine reductases or a cascade of ATP-dependent CoA ligases and N-acyltransferases, this project will lead to the enzyme-assisted construction of large DEL libraries (EnzyDELs) accessing novel chemical space with increased quality. By carrying out selections against disease-relevant targets such as coronavirus-associated proteins (spike protein and intracellular viral proteins) as well as various tumor-associated antigens (mesothelin, tyrosinase), the novel EnzyDELs will be immediately harnessed in the quest to identify much-needed small molecule drugs.",,2025,Institut für Chemie und Biologische Chemie Zürcher Hochschule für Angewandte Wissenschaften,1298023.29,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Rift Valley Fever,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen genomics, mutations and adaptations | Pre-clinical studies",2021 +P28193,221565,MADLID - Machine Learning Driven Liquid Biopsy Biomarker Discovery Platform,"Liquid biopsies-derived biomarkers have shown robust and promising efficacy for diagnosing and monitoring various diseases in a minimally invasive manner as we have seen in recent disease pandemics such as COVID-19 and cancer. However, sensitivity and specificity are one of the biggest issues associated with the current state-of-the-art approaches based on the detection of cell-free biomarkers such as nucleic acids, cytokines, and soluble antibodies. These issues are critical hurdles for physicians to fully harness the benefits of liquid biopsies in their diagnostics and treatment decisions. To tackle this, our novel discovery platform applies advanced machine learning to analyze tissues-specific extracellular vesicles (EVs) in our body to unleash the maximum potential of liquid biopsies diagnostics, real-time disease monitoring, and advanced artificial intelligence to enable reliable and personalized health monitoring and treatments.",,2024,N/A,144187.7,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2023 +P28207,198473,Recoding the SARS-CoV-2 genome - A multidisciplinary approach to generate live-attenuated coronavirus vaccines,"The newly discovered coronavirus (CoV) SARS-CoV-2 is responsible for the recent pandemic of upper respiratory disease and pneumonia that threatens countless lives across the globe. Like all viruses it critically relies on reprogramming of the cellular metabolism, in particular on hijacking the translation machinery of its host. The goal of this proposal is to identify vulnerabilities of the virus during its usurpation of the host cell. Specifically, we will comprehensively test multiple aspects that SARS-CoV-2 may use to hijack host translation. We will use this knowledge to rationally design re-coded coronavirus genomes in order to develop novel live-attenuated coronavirus vaccines. This strategy will not only be applicable for this virus but also for newly emerging zoonotic viruses in the future.Therefore, we will first ask whether the virus hijacks the host RNA modifications machinery to modify its own RNA genome to avoid detection by the host cell's innate immune defense systems. Second, we will identify the host RNA modification machinery that mediates the modification of the viral genome. Third, we will examine whether viral RNA modifications facilitate the recruitment of the host translation machinery. To this end, we will use ribosome profiling and RNAseq in a high-resolution infection time course to quantitatively determine the translational response of the host cell. This will reveal how SARS-CoV-2 exploits the mRNA translation machinery of the host during its life cycle. Fourth, we will test whether the virus modulates the levels of tRNA and tRNA modifications to achieve efficient translation despite the diverging codon usage between its genome and the one of its host. Fifth, we will apply the knowledge gained to develop a series of synthetic attenuated viruses lacking, for example, RNA modifications or containing sequence elements that are difficult to translate during an infection. We will analyze the generated virus constructs both in vitro and in vivo and test selected viruses by ribosome profiling and in animal models. By combining these approaches, we will identify how SARS-CoV-2 interacts with its host and in particular its translation and RNA modification machineries. This will identify attenuated virus variants as well as drug targets and strategies to rationally design attenuated viruses that can be used for vaccine development also for other viruses.This proposal assembles an interdisciplinary team by joining the forces of five labs that combine expertise in diverse areas including molecular virology of coronaviruses, translation mechanisms (including that of viral RNAs), RNA modifications, codon pair deoptimization strategies, high-throughput sequencing, and different animal models for pathogenicity, transmission and immunogenicity. Importantly, our multi-faceted approach will allow us to go beyond the current state of the art, in particular since this team has direct access to live virus samples, various animal models, BSL3 laboratories and animal facilities, and the ability to create recombinant SARS-CoV-2 for experimentation. We are confident that the combined knowledge generated on this new virus can rapidly facilitate vaccine development.Importantly, we will make our initial ribosome profiling and RNA methylation data available immediately after acquisition to speed up research during this ongoing crisis.",,2023,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,1311373.02,Animals | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Pre-clinical studies,2020 +P28208,217579,XVIth International Nidovirus Symposium 2023,"We would like to submit a funding application for the symposium ""The XVIth International Nidovirus Symposium"" taking place from the 14th to the 18th May 2023 in Montreux, Switzerland. (http://nido2023.com).In this five-day symposium, we aim to facilitate scientific exchange and collaboration of high-level specialists in the field of Nidovirology. The Nidovirales is an order of RNA viruses that include the now infamous Coronaviridae virus family, as well as Arteriviridae, Roniviridae, and Mesoniviridae. This eclectic group of viruses including SARS-CoV-2, zoonotic SARS- and MERS-coronaviruses, common cold viruses and many other highly relevant livestock viruses are not only of interest due to their impact on public and animal health but also the economic damage they do. Indeed, as we enter 2023 and the fourth year of the COVID pandemic, the role of specialists in this field cannot be underestimated. The International Nidovirus Symposium has developed over the past 40 years into its present format of a triennial event. It is through meetings like this that multidisciplinary collaborations develop and facilitated the unprecedented reaction to the emergence of SARS-CoV-2. In little more than a year, we went from discovery of a new pandemic virus to the development of functional vaccines and antiviral therapies. This would not have been possible without the groundwork put in place in several interconnected fields over many years. After more than 3 years where scientific collaboration has mostly taken place through the medium of online meetings, it is important to meet face-to-face again to build on existing collaborations but also to develop new connections also in a more informal environment provided by the additional poster sessions, networking dinner and social activities planned during the symposium.With a total of 26 speakers from across the world, we have put together a programme including the leading lights in the field of nidovirology, who will present on a variety of subjects ranging from surveillance and epidemiology, virus biology through to vaccine and antiviral development. Our scientific programme will also address topics such as pandemic preparedness and the response to SARS-CoV-2, discussing what we have learnt, and what we could do better in the future. The strength of this symposium is not only the world-class line-up of speakers but the inclusion of shorter talks, flash presentations and poster sessions where basic researchers will be able to present their work, enabling further interaction with their peers. For our industry partners this is an unprecedented opportunity to interact with the leading scientists in the field, many of whom contributed to the innovative research that led to the fast roll out of SARS CoV-2 vaccines and antivirals. The symposium which will be a physical meeting has been divided up into 4 keynote lectures, 22 speakers, split over 11 sessions as well as shorter 15-minute abstract presentations, 5-minute flash presentation for each and 2 poster sessions. Additionally, a TWiV podcast (This Week in Virology, hosted by Vincent Racaniello http://microbe.tv/twiv) will be broadcast onsite during the meeting.",,2023,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,19664.34,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Community engagement,2023 +P28209,196644,Real-time pandemic functional characterization of SARS-CoV-2,"Real-time pandemic functional characterization of SARS-CoV-2 Background. The outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents the third zoonotic transmission of a high pathogenic coronavirus (CoV) within only two decades. Compared to SARS-CoV and Middle East Respiratory Syndrome CoV (MERS-CoV), that emerged in 2002 and 2012, respectively, SARS-CoV-2 appears to have a lower case fatality rate but is much more able to transmit from human to human. While SARS-CoV-2 genome sequences from patient samples became available within the first two weeks of the outbreak, it took almost two months until virus isolates were made available for reference laboratories and the scientific community. Since phenotypic differences and similarities of SARS-CoV-2 to the high pathogenic SARS- and MERS-CoVs or the low pathogenic common cold human CoVs cannot be deduced from the virus genomes sequences, we urgently need to initiate phenotypic and functional studies on this novel CoV involving infectious virus. Working hypotheses and aims. Of particular importance during the time of the ongoing pandemic is to follow SARS-CoV-2 evolution and to use our established synthetic genomics platform and the established primary human airway epithelium (hAEC) culture system to link genotypes to phenotypes. On a global scale it will be important to carefully link genomic analyses with patient metadata in order to immediately recognize if SARS-CoV-2 variants that arise during the pandemic may have undergone a phenotypic change (aim 1). On the scale of the individual patient it will be important to monitor in-patient evolution of SARS-CoV-2 and host responses in order to identify virus- and host-specific molecular signatures that are associated with mild or severe disease outcome (aim 2). Finally, the obtained data resulting from virus variants will be compared to SARS-CoV and HCoV-NL63, two viruses that use the same cellular receptor (ACE2), and to a set of rationally designed SARS-CoV-2 mutants that lack individual or several accessory genes (aim 3). Importantly, we have complementary expertise and experimental systems that are unique worldwide. We will bridge clinical data, patient samples, coronavirus reverse genetics, and primary human airway epithelial systems, to translate observed virus evolution directly to functional studies.Expected significance. The anticipated results of this project will be highly significant in a number of areas. First, the rapid translation of SARS-CoV-2 genome sequences to functional studies using reconstructed virus variants for phenotypic analyses in primary human airway epithelial cultures will inform if global virus evolution will lead to changes of the SARS-CoV-2 phenotype in the human population. Second, we will determine if SARS-CoV-2 has to undergo an adaptation to be able to efficiently replicate in the lower respiratory tract of patients. This data is important to guide clinicians concerning patient prognosis and may have also a diagnostic value. Finally, we will determine the host response to SARS-CoV-2 and variants in the human airway epithelium in an unprecedented depth by transcriptomics including single cell analyses. This will provide a comprehensive map of host responses that will be particularly informative concerning molecular signatures that drive inflammation and signatures that are associated with disease severity.",,2022,Institut für Virologie und Immunologie Depart. Infektionskrankheiten und Pathologie Universität Bern,494204.65,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Prognostic factors for disease severity | Disease pathogenesis",2020 +P28210,203453,"Disseminating scientific-based knowledge, to foster cultural and behavior changes for combatting environmental and human health impacts associated to antimicrobial resistance during and after covid-19 epidemic in sub-Saharan Africa: case of Congo DR","Since early 2020, the entire humanity has been shaken by a major health crisis due to the emergence of the COVID-19 epidemic, affecting many areas of people lives including public health and socio-economic sectors and the psychological consequences of this unusual situation. It can also have negative environmental consequences, which are likely to lead to other global health crises in the future such as exacerbating the problem of antibiotic resistance, even though, antibiotics do not treat or prevent viral infections like COVID-19. This project proposal is therefore interested in the excessive and inappropriate use of antibiotics during this pandemic in several regions of developing countries in tropical climates, particularly in Sub-Saharan Africa which, according to our surveys carried out in Kinshasa (capital of the Democratic Republic of the Congo (RDC)) in collaboration with the World Health Organization (WHO) and reports from the field, has tripled or even quadrupled between April and November 2020. The population is self-medicating, using antibiotics for the treatment of symptoms and the prevention of COVID-19. According to the results of our research projects before COVID-19 funded by the Swiss National Fund (SNSF), large amounts of bacteria and genes of resistance to antibiotics of the latest generation, in particular classes of beta-lactams and carbapenems, are detected. in the aquatic environment of sub-Saharan Africa particularly in the DRC and southern India. This dissemination is due to several factors, including: (1) the non-regulation of the use of antibiotics in human medicine in the studied regions; (2) the lack of wastewater treatment systems; (3) open defecation; and (4) mostly the lack of strategies for communication, public awareness raising and education, and people practice of scientific results. Given this picture, the following recommendations were made in the context of our results: In addition to reinforcing the regulation for the necessary and appropriate use of antibiotics, the need to promoting the dissemination of our results to experts and especially to the unformed public about the potential impacts of chemical and bacteriological pollutions into water and the spread of pathogens and antibiotic resistance genes. Moreover, according to the WHO, although the COVID-19 pandemic is a current health priority, the existing health crises and diseases should not be neglected, and antimicrobial resistance is one of the global health crises. In this context, it therefore requires urgent attention and action. The methodology applied in our previous SNSF projects for the evaluation of the quality of urban and hospital effluents has an advantage in highlighting the epidemiology of antibiotic resistance in relation to the geographical scale. We integrate existing data from clinical settings showing antibiotic consumption trends to understand the past and present prescriptions/uses of antibiotics. Also, our results from the environmental samples show the global impact of the exposure to antibiotics, including transmission routes based on community behavior rather than on the individual receiving the antibiotics. Therefore, the main objective of this community outreach project is to maximise the impact of our research findings on practice beyond scientific publication in sharing knowledge and our scientific evidence on the issue of antibiotic resistance, in a plain language, to both scientific and non-specialist audiences, raising public awareness for behavior change, educating, and providing appropriate training on antibiotic use. The communication approach will be multisectoral including end-users (public), scientists as well as political authorities. Several communication channels will be used to reach specific audiences, including interactive workshops on implementation of good practice guidelines; field and media campaigns for knowledge mobilisation; advertising materials such as posters, T-shirts, leaflets in local language for the public, electronic and popular media outlets that provide a wider audience than peer-reviewed journals. This project offers a unique opportunity not only to communicate our scientific research results to end-users (public) but also to promote strategies for sharing knowledge to combat antimicrobial resistance through communication.",,2022,Institut F.-A. Forel Université de Genève,54211.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Communication | Indirect health impacts,2021 +P28228,199178,"Promoting the Social State. Statistical Knowledge and Popular Education in Zurich. The Case of the Swiss Social Museum, 1913-1941","""Test of truth for the welfare state"": this is how some media described the challenge that awaited governments affected by the Covid-19 epidemic (Le Temps, May 13, 2020). How to ""absorb the shock"" of a global crisis and how to meet the needs of the most vulnerable categories? These few questions which are now making a comeback in public debate have their origins almost one hundred and fifty years ago, in the aftermath of the Great Depression which struck Western States. If we now know better the complex mechanisms which governed the slow and contradictory development of social protection in Switzerland, as well as the crucial role of the social sciences and their experts in this process (Studer, 1998; Lengwiler, 2002 ), on the other hand, few works have focused on the way in which the idea of ​​a ""social state"" was conveyed in the public sphere and the way in which it was successively formulated, disseminated and appropriated. The history of the Schweizerisches Sozialmuseum (below: Swiss Social Museum or MSS) offers a particularly illuminating case study for understanding this phenomenon. Between 1913 and 1941, the museum occupied a unique place in the institutional landscape of social policy. Neither a documentation center nor a collection of instruments, the MSS was first and foremost a place of experimentation, where new reflections were developed on the modes of production and dissemination of social knowledge. It was also, as this project shows, a place where different conceptions of the social state clashed and where its definitions were negotiated. No historical study has been devoted to MSS to date. Entitled Promoting the Social State. Statistical knowledge and popular education in Zurich. The case of the Swiss Social Museum, 1913-1941, this project for a 12-month return to Switzerland phase at the University of Zurich (UZH) will be largely devoted to it. Beyond a purely monographic history, this research will situate its subject at the crossroads of several disciplinary fields, rarely considered in an articulated manner: the history of social policies and statistics, the history and epistemology of knowledge, finally, visual and media history. Because far from limiting itself to illustrating existing social policies, the MSS has contributed to shaping successive representations of the social state and to objectifying its principles. Thus, the main hypothesis of this research is that the MSS was, for several years, an essential place for the production and dissemination of ""useful knowledge"" (Rauch, 2001) mobilized in the development and implementation implementation of social policies (social statistics, demography, consumer price index, etc.). From a historiographical point of view, this project pursues three objectives: a) contribute to a transnational history of social museums by focusing on the unique place of the MSS within the European ""reform nebula"" (Topalov, 1999). , while contributing to a social and cultural history of statistics in Switzerland; b) make an original contribution to the historiography of social protection through the prism of an institution (the MSS) on the margins of state action; c) develop an epistemological reflection on the conditions for the formation of an ""imaginary of the social State"" based in particular on the use of statistics and its visual representations. The articulation between economic and social history (analysis of institutions, actors and networks), the history of the media (analysis of museographic systems) and the history of statistics (analysis of the numbering of society ) brings heuristic added value which constitutes the originality of my approach. This project is part of my current research on the history of data visualization, while extending towards the fields of economic and social history . At this stage of my career, it will allow me to formalize my own theoretical approach, at the crossroads of the different disciplines that have informed my research to date. Innovative from the point of view of its subject, as well as the methods used, it constitutes an opportunity to develop my network in German-speaking Switzerland, to establish new collaborations and to strengthen my career prospects in Switzerland and internationally. """,,2022,N/A,124686.14,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2021 +P28233,200878,Religion and spirituality of seniors in times of Covid,"In addition to the direct threat to physical health, the current COVID pandemic crisis appears to have a considerable impact on mental health, well-being and quality of life. The studies published on this subject are still few in number and present rather contradictory results concerning the impact of the crisis on the psychological health of the elderly, the first and main victims. Furthermore, studies show that the crisis we are experiencing can lead to the use of religion and spirituality to try to overcome the anxieties and fears generated by the pandemic. In Switzerland, where the space granted to traditional religious institutions continues to shrink, religion and spirituality still retain an important place for a majority of the population aged 65 and over. In this context, it is fundamental to study what resources older people used during semi-confinement and are currently using to face the health crisis and what role (positive/negative) spirituality and religion have in their experience. However, to our knowledge, no Swiss study has focused on the potential impact of these dimensions on the health and well-being of older people during the current crisis. The main objective of this research project is to better understand the potential role of spirituality and religion for mental health, morale, well-being and quality of life, as perceived by people aged 65 years and over living at home, during the current pandemic crisis. Four specific goals have been defined: (1) Identify the impact of the pandemic on the mental health, morale, well-being and quality of life of people aged 65 and over; (2) Identify the resources (psychological, social, religious and spiritual) mobilized by seniors to cope and identify possible changes in religious/spiritual beliefs and practices following the current situation; (3) Deepen knowledge of the role of spirituality/religion in volunteer engagement, and more specifically in the engagement of seniors with other seniors; (4) Identify possible needs and expectations, in terms of spiritual support, of elderly people receiving home care during the current crisis and establish whether the offer provided by support systems for seniors, that they whether institutional or associative, could be improved with regard to the spiritual and religious experience of CMS clients. In order to achieve the desired objectives, the qualitative approach is favored for data collection (semi-structured interviews and focus groups). This approach seems to us to be the most appropriate for studying in depth sensitive themes such as religion and spirituality as well as those of emotions, often negative, and the experiences of elderly people in times of pandemic. In parallel with the interviews, the focus groups will allow us to address the themes in question in an interactive manner while encouraging discussion and debate. As for data analysis, a mixed and multidisciplinary approach will allow us a better understanding of the dynamics, realities and contexts linked to our problem. We thus hope to shed broad and rigorous light on the impact of the COVID crisis on elderly people living at home and the possible role (positive or negative) that religion/spirituality plays for them in coping with the current health crisis. Through this project we also hope to contribute to the reflection on what is important to put in place in the years to come in connection with policies to keep elderly people at home for as long as possible. In a society where the population is increasingly distancing itself from traditional religious institutions, it is necessary to be well aware of the expectations, in terms of spiritual support, of seniors at home (whether their mobility is intact or reduced). We also hope that the integration of seniors in research as active co-constructors of reflection and the development of solutions will not only contribute to improving the adequacy of these solutions to the reality of their daily lives, but will participate also to improve social recognition regarding their contribution to the well-being of society.",,2023,Institut de sciences sociales des religions ISSR - FTSR Université de Lausanne,169190.39,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P28237,216760,COVID-19 IN PREGNANT WOMEN IN MIDDLE EAST,"The purpose of the present application is to demand an extension for the existing grant IZSEZ0_213489, for a scholar, Prof Sayed Mousavi, already hosted at the University Hospital of the Canton of Vaud (CHUV) with a placement currently ongoing and funded by the SNSF (cf confirmation letter below).",,2024,Office International Relations University of Lausanne,67839.73,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2023 +P28238,213489,COVID-19 IN PREGNANT WOMEN IN MIDDLE EAST,"To gather a large dataset, we launched an international online registry, named ""COVI-Preg"", providing a structured data collection tool available to any facility assessing pregnant patients for SARS-CoV-2 infection. A registration website is accessible at www.covi-preg.ch giving collaborators an access to the REDCap data collection platform available online at https://redcap.unisante.ch/ . After COVI-Preg was published in THE LANCET (PMID: 32353329), we gathered more than 150 centres worldwide including through Prof Mousavi, who provided very interesting data from Afghan pregnant patients exposed to SARS-CoV-2.Prof Mousavi data on Afghan pregnant women will also be beneficial to our hospital. He will bring important additional data to COVI-Preg as well as his expertise in molecular biology and biochemistry. His research is very complementary to the research we are currently conducting.",,2023,Office International Relations University of Lausanne,95226.37,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2022 +P28240,210054,Poverty and social security in time of crisis - lessons (to be) learned during the covid19 pandemic,"To contain the Corona virus, governments around the world had to take measures that resulted in restrictions on public and economic life. Such measures were also taken in Switzerland and were particularly drastic in the initial phase of the pandemic (spring 2020). In international comparison, these interventions were less severe, and the economic consequences were cushioned by means of various social benefits such as the expansion of short time work or hardship compensation. Nevertheless, some sectors and groups were hit hard. Among them, low-skilled and poorly paid workers, who were already in precarious living conditions before the pandemic. These groups were affected more than average. The self-employed, who are particularly dependent on face-to-face exchanges, were also severely restricted in some cases. In addition, studies in Geneva and Zurich showed that the need for direct food supply increased rapidly at times and that especially groups of foreigners with unregulated settlement permits and difficult access to social benefits found themselves in a precarious situation as a result of the pandemic. In contrast, economic sectors in which highly qualified people work were far less affected, or these sectors received an additional boost thanks to the pandemic (Pharama, IT). According to current knowledge, the beginning of the pandemic in particular, with the partial lockdown, has exacerbated socioeconomic inequalities in Switzerland. However, much remains unclear. What medium-term and long-term effects are associated with the pandemic has not been researched. It is also unclear how efficiently the social safety net protected the population. Since existing studies use sample data, this is associated with some limitations. Detailed evaluations would be important that could show short- and medium-term effects and address particular risk groups of the pandemic. The effectiveness of the social safety net, taking into account the federal organization of Switzerland, has also not been conclusively clarified. This knowledge could be used to find out how pandemic measures can be taken without threatening vulnerable groups and exacerbating existing inequalities that endanger social cohesion. Against this background, the outlined project proposes two research parts that relate to and complement each other. In the first part, we will use linked tax data to examine the economic consequences of the pandemic and the effectiveness of state assistance, focusing on dynamics around the threshold of livelihood security. Using data from 6 cantons, we will be able to examine the situation of around 3.5 million people in Switzerland for the years 2019 - 2022. Thanks to the research cooperation with a French-speaking poverty expert, a comparative analysis can be carried for German and French speaking cantons. For efficient data acquisition and valid analysis, previous knowledge from various SNSF and contract research projects can be used. A research cooperation with the University of Bern (Prof. Dr. Ben Jann) is planned for this purpose. The second part of the project will focus on the clientele of Caritas Switzerland. Caritas Switzerland is the largest NGO in Switzerland with 16 regional branches. Between March 2020 and December 2021 more than 100,000 people have been supported with 18 million. The support comes into play above all when government instruments are not (yet) effective. Reporting's by Caritas Switzerland so far allow only little information about the people who have received support. This is a missed opportunity, as systematic data-collection on the frontline could provide timely information on the poverty situation of the population and gaps in social protection. In the second part of the project, therefore, more will be learned about the work of Caritas Switzerland during the Covid 19 pandemic by means of analyses of the existing case data and with the help of expert interviews. The core of the second part, however, is the development of a poverty-monitoring tool that can be used for timely strategic management and, in the event of a next crisis, as a national early warning system. This will improve crisis management considering disadvantages people in Switzerland drastically. Close cooperation with Caritas Switzerland ensures the transfer of knowledge into practice. There is also close cooperation with the Federal Social Insurance Office (Dr Philipp Dubach). He provides the link to experts in the federal administration who can comment on the project work and take the results into account when evaluating the Covid-19 protection measures from the perspective of social inequality.",,2026,Departement Soziale Arbeit Berner Fachhochschule,532617.79,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2023 +P28250,207294,Ritual-theoretical and religious-aesthetic analyses of the Basel Fasnacht (including field research in the period marked by the Covid pandemic),"The state of emergency in social life that has existed since the Corona pandemic has had a profound impact on public rituals and festivities. This raises fundamental questions about the nature of such rituals and festivals, in particular about their ability to change and adapt. Crisis events of such magnitude represent a unique field for research into innovative processes in post-secular societies, in particular the transformation processes of religious rituals in public. Methodologically, the research project is based on the religious-aesthetic questions and analyses on the interpretation of religious dimensions of the applicant's society on the one hand, and on the scientific observation of the Basel carnival by the visiting scientist Olga Cieslarová, which has been carried out for twelve years, on the other. The combination of these two perspectives should make it possible to describe the perceptual space of the carnival from a religious-aesthetic point of view and to analyze the new ritual developments using the classic ethnographic tools and the method of participant observation. The main lines of the project are: (a) field research on the Basel carnival during the corona pandemic, (b) theoretical and practical training of students at the University of Basel based on this research, (c) religious studies processing of the planned field research, namely: two seminars at the University of Basel, a study day ""Basel Carnival, Ritual and Religion"", a public symposium with presentation of the field research, an interdisciplinary specialist congress, preparation for the publication of an anthology ""Carnival, Religion, Ritual"" and a separate scientific article on the topic ""Basel Carnival, Ritual, Tradition and Innovation during the Pandemic"".With a few exceptions, the Basel carnival has not yet been the subject of academic reflection. The project presented is intended to make a contribution to establishing carnival research more clearly as an academic field in religious studies. International academic cooperation will also be initiated, followed by research presentations at conferences and publications (Fribourg: Ritual Creativity Conference, Prague: Symposium on Public Festivity, USA: Annual Meeting of American Academy of Religion). With the help of the analysis of the historical development of carnival in the 20th century and current field research, the core characteristics that give public rituals their adaptability and resilience will be analyzed. The hypothesis is that the ability to integrate innovations in small steps is crucial. The current exceptional situation makes it possible to observe corresponding ritual processes in a realistic way and to test the aforementioned hypothesis. The project focuses on innovations and creative implementations that have a significant influence on the future development of public festivities and rituals.",,2022,Fachbereich Aussereuropäisches Christentum Theologischen Fakultät Universität Basel,22017.13,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P28252,196212,Compliance With National COVID-19 responses and measures (CoWiNaCo),"This research proposal answers the Special Call on Coronaviruses that the SNF has opened on March 4, 2020. With the ongoing crisis, all states have taken measures to mitigate further spread of the disease. A major concern in the public, political and expert debates on these national responses is the question of compliance: Does, to what extent and why the population comply with crisis directives, including the mobility restrictions such as social distancing or confinement? This question is of utmost importance as counter measures against COVID-19 can only be effective if target populations indeed follows the instructions and abides by the rules.This question is at the core of the field of compliance research in public policy studies and refers to two major compliance subjects: the implementing sub-national units (such as the Swiss cantons) and the target populations that in the COVID-19 case is identical with all inhabitants of a country. We propose to study the factors leading both to compliance and to noncompliance with COVID-19 counter measures by comparing Switzerland, Israel and the USA. The research design consists of a qualitative case study design with two sets of comparisons: First, we test the member state compliance hypotheses in the USA and in Switzerland with Israel as contrasting control case; and second, we test the citizen compliance working hypotheses in all three countries, focusing on the comparison between Switzerland and Israel with USA as contrasting control case.The selection of three countries follows an adapted compound research design with contrasting least likely cases: Switzerland and USA are comparable as both are highly decentralized federal states with extensive subnational member state autonomy. This means that subnational member states can change, customize, gold-plate or even compensate central government policy in order to adjust it to their needs. However, it also means that public policy is scattered and fragmented in such systems. Subnational member states in this study therefore always refer to either the Swiss cantons or the American states. Israel is a centralized system and thus serves as the contrasting case. Switzerland and Israel then are comparable as both are about the same size. The USA is the contrast case. Moreover, the three countries responded to the crisis differently in terms of when measures started and in terms of the severity of the measures taken. We use the two comparative settings to better understand citizen compliance and noncompliance: who complies and who does not? Why? What are the drivers of compliance, what hinders compliance, and what contributes to noncompliance?We expect to find relevant insights in answering the following questions: -First, what factors foster citizen compliance with drastic measures and what factors hinder it or encourage noncompliance?-Second, how can we foster subnational member state compliance in order to achieve a coherent policy response in federalized systems. Alternatively, in the case of government failure at the central state level, how can we achieve coherent and adequate policy responses at the subnational member state level in times of crisis?The project responds to the following priority areas of the call:-The societal impact at large [...]; -Impact of official and social media communications on [the] behavior of policy makers, health care workers, patients and populations; -The social and political history, including for instance public communication, legal aspects, border controls, mobility restrictions by States of COVID-19 disease; -[...] response systems and crisis management [...]",,2024,Kompetenzzentrum für Public Management Universität Bern,330933.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Community engagement | Policy research and interventions,2021 +P28258,214548,The Impact of COVID on International Disputes,"With little warning, COVID-19 quickly escalated into a generational crisis, creating sustained havoc seen perhaps only in past cases of war, attack, and natural disasters. In the bedlam of the early months, health, science, political, and economic communities were hit with sudden force, required to quickly shift and rearrange the normal order of work. In arbitration, leaders took imperfect information to make dramatic decisions. In process and procedure, arbitral institutions, arbitrators, legal counsel, and clients were swept into this turmoil. In some cases, bold initiatives, still in design and testing, were quickly put into service, upsetting norms and traditions and the very notions of traditional process.The Impact of COVID on International Disputes includes contributions from legal practitioners and academics, takes a fresh look at issues addressed in international arbitration during the COVID-19 pandemic, gathering best practices, additional perspective and predictions based on current practices that will help parties, legal counsel and arbitrators in the future.",,2023,Droit international public Faculté de droit et des sciences criminelles,11478.64,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Other secondary impacts,2023 +P28272,201368,Transformation of waste management practices and policies in South Asia during and after the COVID-19 pandemic: Impacts on gender equality and sustainability,"Municipal solid waste management (MSWM) has been transformed during the COVID-19 pandemic. On the one hand, MSWM has been declared as an essential service showing the dependence of cities on functioning systems; on the other hand, waste collection, transportation, recycling and treatment have been identified as potential vectors of viral transmission. This project investigates MSWM systems in Nepal and Sri Lanka during and after the COVID-19 pandemic; its gendered impacts on formal and informal waste workers, their livelihoods, health and stigmatization; and its gender and sustainability effects on household waste practices. It also examines longer-term impacts on changes in waste policies and discourses. The comparison between Nepal and Sri Lanka aims to contribute to a better understanding how the pandemic shaped social practices, gender relations and waste policies in view of sustainability, urban resilience and gender justice.",,2025,Institut de géographie et durabilité Faculté des géosciences et de l'environnem. Université de Lausanne,534495.26,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P28274,209885,Intergenerational cohesion during COVID-19 and beyond,"The COVID-19 pandemic has shaken society to its core. However, while its profound impact on health and healthcare systems became immediately visible, we are only now starting to grasp its massive toll on individual and collective welfare. One area in which this societal harm has become apparent is intergenerational contacts. This applies particularly to contacts between older people (aged 65+ years) and younger people (aged <65 years). The pandemic has had various consequences for the support systems between people of different age groups. On the one hand, COVID restricted the possibilities to help, due to the contact regulations. On the other hand, the pandemic also resulted in an increased willingness to provide assistance between and within generations. The social cohesion was nevertheless strongly challenged by the fiercely diverging views on how to handle the (protective measures during the) pandemic. To investigate this societal dimension of the pandemic, we will examine the building and maintenance of inter-(intra)generational social cohesion. Therefore, we use a triangulation of qualitative and quantitative methods, including secondary analyses of existing European (SHARE) and Swiss (SwissSurvey65+) data sets, stakeholder workshops and sounding board meetings, an original national survey (1600 participants aged 18+ years) and in-depth interviews (N = 34) with both private people of various ages and professionals who work with older persons. In this project, we cooperate closely with various national practice partners (i.e. Swiss Red Cross, Canton of Bern; Catholic Church, Region of Bern; Pro Senectute beider Basel; and Intergeneration.ch) who have gathered comprehensive experience in upholding inter-(intra)generational relationships during the COVID-19 pandemic. The project's aim is twofold. First, we aim to map and evaluate the various innovative ways in which people have established intergenerational relationships and social cohesion during the pandemic both in informal and professional contexts. In doing so, we will identify the factors that have affected the societal handling of the pandemic. Second, based on these research findings, we will formulate policy recommendations to strengthen intergenerational societal cohesion. As such, the pioneering experiments for establishing contact in the challenging COVID-19 context will prove valuable lessons learned to boost the intergenerational cohesion in the post-pandemic era.",,2026,Institut Integration und Partizipation Hochschule für Soziale Arbeit Fachhochschule Nordwestschweiz,497065.52,Human Populations | Other,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28275,201385,The Swiss Transplant Cohort Study (STCS),"The STCS is an investigator-initiated, multisite, national cohort study with a primary interest in clinical research and quality control of outcomes and clinical care. Although the STCS has been operative in accordance with applicable laws and regulations since its initiation, the STCS adapted all documents and process according to the new (2014) Swiss Human Research Act (HRA) and its Ordinance (HRO). As an important milestone, our regulatory amendment was accepted on a national level in November 2019. In this respect, the STCS plays a pioneering role among the national cohorts in Switzerland. Moreover, in 2018 the STCS started to involve patients in the Scientific Committee and representation of patients in governing committees is foreseen in the coming years.The STCS was operationally as successful in the current funding period as in previous periods. Between May 2008 and June 2020, 6141 transplantations have been performed in 5879 patients of which 290 were pediatric patients. By end of June 2020, the size of the active cohort was 4839 patients. This important figure corresponds size of the cohort actively followed by the centers on an everyday basis. A total of 149 scientific project are completed or currently run on the data. More than 30 national or international collaborations are in place. Seventy peer-reviewed papers were published or are accepted in total. Representatives of the Swiss Personalized Health Network (SPHN) have become members of the STCS and a close collaboration with the Swiss Biobanking Platform (SBP) is established. During the current funding period, the different working groups achieved 22 of 33 previously stated milestones. The reminder could not be pursued or are yet ongoing. The Data Center is the responsible provider of the STCS data infrastructure. The main tasks include the management of the complex data structure of the STCS, to provide comprehensive public outcome reporting and to support researchers in data management and statistical analysis. In 2020, the data center took moreover the responsibility to act as the scientific IT provider after our current provider had decided to gradually discontinue its activities. Professional data services are essential for the STCS since transplantation is a highly complex medical intervention. Complex processes range from donor recruitment, organ allocation, and organ procurement, to the process of transplantation and post-transplant care. Distinct systems are interrelated and making demanding data integration processes necessary. The STCS is operating a decentralized, center-based Biobank of recipient samples. Since its creation, the STCS harvested 14'448 plasma, 14'297 viable cell samples and 5791 DNA samples in consenting patients. Fifteen percent of all nested projects (NP) used the Biobank over the past years. The genetic dataset of the STCS has been enlarged to 3000 patients with genome-wide data, making the STCS one of the largest cohorts of SOT recipients with long-term follow-up, accurate clinical-, psychosocial-, and genome-wide data. STCS data are available 'open access' for research within the framework of the Scientific Committee guidelines and upon EC approval. Next funding period:The current application involves a research-oriented Data Infrastructure and Service (DIS). The described scientific aims only represent a crude summary of the working groups' aims and of the aims of the DIS. In the next period, the scientific strategy of the STCS will mainly consist on consolidating its current scientific groups and study domains, and to build upon and expand on new and timely issues that have become important in transplantation. Moreover, new research initiatives in the personalized medicine area will represent a key aim in future research. The STCS is well positioned to contribute significantly in this regard due to important structure work and networking that took place during the last years. Hence the focus of our research will be on traditional and deep learning methods. A further aim will be to assess the role of Covid-19 in immunosuppressed SOT recipients. A successfully launched SNF-supported platform trials project in collaboration with SHCS is in the set-up phase. A large update of the immunology datasets and the implementation of a new, integrated phenotyping system will add to the clinical interpretation of our transplant immunology research and the use of genetic data to predict immunologic phenotypes is planned. This shall be achieved through candidate gene studies or GWAS. The interdisciplinary Psychosocial Interest Group (PSIG) will analyze psychosocial and behavioral outcomes over the transplant continuum and invest in innovative e-health supported care models allowing personalized health approaches. The Oncology group plans association studies across various types of transplantations and evaluates the progression frequency of patients with previously known monoclonal gammopathy. In collaboration with the STCS Psychosocial Interest Group (PSIG) the oncology group plans to collect information on SOT patients subsequently developing cancer and their risk of poor quality of life and psychosocial status.The Data Center will mainly be in charge of further developing the data infrastructure and services. This includes the following core tasks and challenges: -Development of a structure for the sharing of sensitive patient data between transplant hospitals and the STCS. The SPHN/BioMedIT supported IDEAL project plays a key role in this process.-Implementation of semantic interoperability standards and FAIR principles. Due to the complexity and the new territory for a patient-centered research system, the STCS proposes to conduct the 'STCS semantic mapping and FAIRification project"".-To develop and extend support services for researchers that enable them to better manage the complexity of the STCS data. A not-for-profit system for reimbursement will be developed. -Development of services provided to patients (mobile health applications)The STCS Biobank plans important developments regarding standardization, FAIR principles implementation and a new personalized sampling approach:-A certain limitation in the current sampling scheme of the STCS is that sampling is solely based on fixed sampling time-points. A novel approach plans to expand the current scheme with an additional event-triggered sampling protocol. This will allow a more personalized sampling alongside of relevant events -Participate in the eCatalogue project of SBP and adopt FAIR principles to improve the findability of samples-Standardization of the preanalytical processesTransplantation medicine often offers the only solution for patients with end-stage organ failure and is in the public interest with its central ethical questions about organ donation and limited organ availability. The field of transplantation medicine is of importance and will be of continued significance in the future. The STCS, together with other institutions, makes a central and important contribution to this field.",,2024,Klinik für Transplantationsimmunologie und Nephrologie Universitätsspital,5700382.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P28276,198265,Development of a microfluidic platform for real-time detection of SARS-CoV-2 virus based on multifunctional silica membrane biosensors,"After initial emergence in the Hubei province of China in the last months of 2019, the coronavirus disease 2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread all over the world, thus resulting in a major threat to the global public health security. While aerosols, such as respiratory droplets emitted by the cough and sneeze of symptomatic patients, were identified as the main transmission vectors, asymptomatic patients in incubation period also constitute possible transmitters of the disease. With around 5,000,000 confirmed cases and 330,000 deaths worldwide caused by the COVID-19 pandemic, there is an urgent to develop a set of measures for controlling the spread of the virus, decreasing the severity of the pathology in infected patients and eventually preventing infections by efficient vaccines. The development of accurate, cost-efficient and rapid screening and diagnostic methods is of crucial significance to slow down the circulation of the virus. In particular, the possibility to overtake the present qRT-PCR gold-standard for virus detection by point-of-care (POC) devices which do not rely on specialized personnel and access to biomedical laboratory environment, would bring a real breakthrough to control the spread of COVID-19. Here, we propose an alternative approach to overcome the limitations of the current testing procedures which should eliminate the need for biomedical personnel, specialized laboratory infrastructure, pre-testing sample preparation, additional reagents and bench-top instruments. Based on the expertise of one of the application partners in the design and production of automatized microfluidic devices combining isolation, detection and analysis modules, we propose an interdisciplinary approach for the development of a cheap and ultra-sensitive biosensor, based on porous silica (SiO2) supported active sensing surfaces, for direct viral RNA targeting. The following criteria will be addressed:-Portability: development of a miniaturized, fully-automated microfluidic device integrating all steps of the process within a single system architecture (RNA inactivation and extraction, sensing, readout of the hybridization events); without the need for additional reagents or external instruments;-Sensitivity: the versatility of the functionalization process to engineer porous SiO2 membranes conjugated to nucleic acid probes will allow for the optimization of several parameters determining sensing sensitivity (density and orientation of surface probes, covalent or non-covalent immobilization, discrete or multivalent attachment sites);-Reliability: four target nucleotide sequences will be selected, applying strict filters for probe uniqueness, probe-to-target duplex stability and similarity to non-target sequences;-Screening efficiency and specificity: the design of the microfluidic device will allow for multiple probe sequences to be tested in parallel; -Cost-effectiveness: production of the active sensing surfaces will make use of non-expensive materials and synthetic protocols; the readout step (DC resistance and bioimpedance) does not require additional reagent or labelling agent.These novel biosensors are expected to greatly enlarge the implementation of diagnosis units in non-medical environment such as airports, train stations and ports, where the fast screening of international travelling population would contribute to the early identification of potential vectors and would thus help in containing the disease propagation. Also, the tracking of asymptomatic transmitters will be highly facilitated by the development of cost-effective and portable testing devices. In future perspective, the proposed methodology could be applied to the detection of multiple pathogens within a single sample, thus enlarging the diagnosis scope of such system.",,2023,Group for Functionalized Biomaterials Institute of Chemical Sciences & Engineering Ecole Polytechnique Fédérale de Lausanne,1184882.63,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P28291,211129,Proximity-Sensitive Awareness in Epidemic Modelling,"In global epidemics, such as the SARS-CoV-2 epidemic, people often receive information about proximity of the new infectious cases either through government reporting or through word of mouth. However, the impact of this proximity information on the dynamics of the preventive behaviour (Behavioural Impact, shortly, BI), and consequently on the epidemic propagation (Epidemiological Impact, shortly, EI) is not understood. Previous research aims to understand the EI by proposing simple mathematical equations for the BI (we call these awareness models), and most of these works assume that individuals only have access to global infection counts, and no proximity information. The ongoing SARS-CoV-2 epidemic acts as a natural laboratory, enabling us observe the BI and the EI of proximity-sensitive awareness (PSA) in real datasets, and motivating the mathematical analysis of the EI of new awareness models. Objectives and methods: I propose to carry out a complete methodological cycle from innovative data collection methods to rigorous mathematical proofs and the evaluation of practical implications for improving current epidemic containment methods:1. Observe the BI and the EI of PSA in psychological and epidemiological datasets.2. Implement PSA into simple network-based (SIR and SIS) epidemic models based on the results of Objective 1, and observe new phenomena about the EI of PSAs from a statistical physics perspective by computer simulations. Special focus will be given to understanding the early growth of the number of infections and the density the infection in the endemic state, which are crucial properties of real-world epidemics.3. Rigorously prove the most important discoveries made in Objective 2 by extending the related mathematical work on branching processes.4. Explore the practical implications to improve current epidemic containment methods based on the discoveries of Objectives 1-3.Outcome: A successful completion of these objectives will advance the theory of awareness modelling in a multidisciplinary way.",,2024,Department of Network and Data Science Central European University PU,112148.87,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Austria,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2022 +P28292,198345,Protective and Pathogenic T Cell Immunity During SARS-CoV-2 Infection,"The current pandemic coronavirus disease 2019 (COVID-19) with the newly emerged severe acute respiratory syndrome (SARS) coronavirus SARS-CoV-2 causes grave challenges to the medical and economic systems and to people world-wide. Besides massive measures to contain the pandemic, intense efforts are ongoing to identify drugs that could be used as antivirals and also vaccines that may protect the many individuals that have not yet been infected, particularly those at high risk of suffering severe clinical courses. Towards vaccine development and to understand factors related to organ/tissue involvement, it is paramount to analyze adaptive immune responses against the virus with respect to protection but also regarding cross-recognition of self-/autoantigens from different tissues and the involvement in organ pathologies. CD4+ T cells are critical for helping efficient cytotoxic CD8+ T cell responses and also neutralizing antibody production. They are also the main mediators of autoimmune reactions. Here, we propose to use a unique and completely unbiased epitope discovery approach for the identification of immunodominant target antigens (viral and self-antigens) for SARS-CoV-2-specific CD4+ and CD8+ T cells. Our methodology allows the identification of the specific target epitopes and to assess, which T cell responses are broadly SARS-CoV-2-reactive and likely protective against the prototype isolate, other SARS-CoV-2 isolates and putatively even other coronaviruses. Furthermore, it systematically identifies, which autoantigens are cross-recognized by SARS-CoV-2-specific CD4+ and CD8+ T cells. We will characterize SARS-CoV-2 CD4+ and CD8+ T cell clones after SARS-CoV-2 exposure and different disease courses with respect to immunodominant epitopes, cross-reactivity with autoantigens, phenotype, and function. New targets will be validated in larger cohorts post-infection. The antigen discovery approach will allow to address if immune responses are involved in clinical manifestations, for example prolonged course of infection due to inefficient immunity or, conversely, organ pathology such as pneumonia, pulmonary fibrosis, endotheliitis, or nervous system manifestations due to an overshooting/pathogenic immune response.",,2023,Neurologische Klinik Universitätsspital Zürich,686774.17,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +P28294,207264,Prevalence of and Pathways to Non-Medical Use of Prescription Medications Among Adolescents and Young Adults in Urban Switzerland,"Non-medical use of prescription medications (NUPM) is on the rise in the Western world, especially among adolescents and young adults. In numerous countries, NUPM has increased during the COVID-19 pandemic. Many young people assume that prescriptions are safer to use than illicit substances. After all, they are prescribed by health care providers and dispensed by pharmacists. Accordingly, many young people engage in NUPM for recreation, self-medication, or self-enhancement. In reality, however, NUPM is linked to a variety of adverse health outcomes. It is also associated with an increased risk of problematic substance use patterns, including polysubstance use (e.g., NUMP along with use of alcohol or additional psychoactive substances). To effectively prevent NUPM, it is essential to understand the characteristics of young people at increased risk for this behavior, but research on pathways to NUPM in Switzerland is scarce. Indeed, even the prevalence of NUPM among young people in Switzerland is not well-understood, as are recent changes in NUPM due to the COVID-19 pandemic. The proposed PhD project addresses these gaps by drawing on and contributing to three large-scale community-representative datasets of young people, subsuming a total of ~55,000 participants (Zurich Youth Survey, The Zurich Project on Social Development from Childhood to Adulthood, Monitoring the Future Study). NUPM will be assessed with self-report, hair, and wastewater data, including items devised by the applicant. Data on NUPM will be available from before, during, and (presumably) after the COVID-19 pandemic. Three broad developmental pathways to NUPM from childhood to early adulthood will be examined: early substance use, psychopathology, and social pathways. This project will provide novel insights into the prevalence of and pathways to NUPM, which is key for developing effective prevention and interventions. With the inclusion of data from the United States, it will also provide an in-depth look at NUPM in an international context.",,2026,Jacobs Center for Productive Youth Development Universität Zürich,262724.05,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P28298,221961,Target trial emulations to bridge the evidence gap between COVID-19 treatment trials and observational cohorts - from application to guidance,"Background: The COVID-19 pandemic resulted in many deaths worldwide and remains an important cause of death in the unvaccinated, those with comorbid illness, compromised immune function, or older adults. Randomized clinical trials (RCTs) evaluated various treatments for COVID-19, such as the antiviral remdesivir or the janus kinase inhibitor baricitinib, and their results were subsequently synthesized in systematic reviews and meta-analyses. However, most of these RCTs were conducted before widespread circulation of the current virus strains, among unvaccinated patients, mostly patients with adequate immune function and studied short-term outcomes only. Current clinical guidelines lack evidence-based guidance for several important hospitalised populations. Target trial emulations (TTEs) offer a comprehensive causal inference framework to assess comparative effectiveness of treatments and can answer additional clinical questions in areas where RCTs are not available, not feasible, not ethical, or not timely. Objectives: The objectives of my research project are twofold. First, to provide updated treatment effect estimates for remdesivir and baricitinib among hospitalized COVID-19 patients, focusing on vulnerable populations and long-term outcomes (Objective 1). Second, to establish infrastructure (Ancillary Objective 1.1) and guidance (Objective 2) for future TTEs on hospitalised patients affected by emerging infectious diseases.Methods: For Objective 1, I will collaborate with the OpenSAFELY Trusted Research Environment (www.opensafely.org), which contains National Health Service data from 40% of the English population, linked to secondary care data and other national registries. I will conduct several TTEs to answer the clinical questions of this objective and benchmark the analyses to my own individual patient data meta-analyses. For Ancillary Objective 1.1, I will conduct a mapping review to identify other suitable secondary care cohorts for TTEs in infectious diseases. Regarding Objective 2, I will extend the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool to assess the risk of bias in causal inference studies.Output, Impact, Outlook: The findings will be published in peer-reviewed journals and presented at scientific conferences. The TTEs will provide lacking evidence for clinical guidelines. OpenSAFELY has been a major source of innovative and robust scientific output directly impacting policy in the field of COVID-19. The mapping review will provide a comprehensive overview of databases for future TTEs, and the ROBINS-I extension will provide researchers with guidance to assess risk of bias in TTEs and other causal inference studies. This project will enable me to complement my RCT and meta-analysis knowledge with advanced causal inference skills on an applied (Objective 1) and meta-research (Objective 2) level, collaborate with pioneers in the field of TTEs, expand my international scientific network, conceptualise future collaborative research ideas, and eventually build up my own research group on return, applying for an SNSF Ambizione grant.",,2026,Bristol Medical School Bristol Population Health Science Institute,126476.31,Human Populations | Other,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United Kingdom,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2024 +P28317,204636,C-type lectin receptors and their implication in the innate response against respiratory pathogens,"Respiratory pathogens are known for giving rise to periodic pandemic outbreaks. The innate immune system senses these pathogens via different receptors, among which, the C-type lectin receptors recognize specific pathogen-associated carbohydrates. Previous studies have demonstrated that one of these receptors, SIGN-R1, has exquisite pathogen-recognition capacities, detecting not only viruses, but also bacteria and fungi. In addition, SIGN-R1 plays a crucial role in the activation of the initial inflammatory response, which is instrumental in the pathogenesis of these diseases.Therefore, the main goal of this project is to study how the C-type lectin-mediated inflammatory response initiated against the respiratory pathogens influenza, Streptococcus pneumoniae (Objective 1) and SARS- CoV-2 (Objective 2), affect the outcome of the disease. In addition, we will investigate new approaches aimed at using C-type lectins as therapeutic targets (Objective 3). Amongst them, we will develop SIGN- R1 chimeric molecules, such as SIGN-R1-C3d or SIGN-R1-Fc, intended to opsonize the pathogen and direct it towards a specific type of immune cells. Moreover, we will design and evaluate different therapies intended to promote or inhibit the SIGN-R1-mediated inflammatory response in the course of an infection or during vaccination. Finally, we will also develop nanocarriers specifically targeted towards SIGN-R1- expressing cells.In the last five years, our group has published a series of papers characterizing the innate response to respiratory pathogens. During these studies we have developed a unique toolbox of in vivo and in vitro microscopy techniques, including intravital 2-photon microscopy, as well as other immunology and microbiology-based methods that will be used in this project. Additionally, we will take advantage of our network of international experts in pharmacology and molecular biology to design the new compounds with a potential therapeutic use against influenza, S. pneumoniae and SARS-CoV-2. The successful completion of this project will provide significant benefits to the fields of vaccinology and infectious diseases, especially regarding the modification of the inflammatory and humoral responses against a specific antigen as well as the neutralization of the pathogen. Moreover, our results will be valuable to understand the role of the early inflammatory process in the immune cell-pathogen dynamics in other major respiratory diseases.",,2026,Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice,947501.42,Bacteria | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2022 +P28318,199667,The many faces of contagion,"Many citizens-in the face of the recent SARS-CoV-2 pandemic-have looked at science and researchers for answers. However, they clashed with the inevitable incertitude and complexity of the scientific process and revived the complex debate between science, politics and society. A simple virus, tens of times smaller than bacteria, has rekindled ancient fears of disease and death. The situation has highlighted the delicate matter of forced isolation, which is necessary to prevent disease but causes loneliness and seclusion. We have realized that humans, by nature, need interaction with others. We need to exchange ideas, be influenced by new trends, get to know different cultures, have a contagious laughter-all together. Therefore, contagion has a dual meaning: with respect to viruses, it becomes something frightening, but with respect to our anthropological peculiarities, it becomes something indispensable. This duality is the common thread of our project: on the one hand the complex journey of science in the fight against pathogens, on the other hand the centrality of contagion in human relations, evolution and culture. Although a pandemic originates from the meeting of a pathogen with an organism, it acts not only on the biological dominion but it spans to the entire society (behaviors, protective measures, isolation, political decisions, etc.). It is from this context that the project ""The many faces of contagion"" stems.We intend to develop an exhibition, educational paths for schools and a series of related events. We will start from the scientific competences of biologists to then enlarge the reflection to the term ""contagion"" in a broader sense. Starting from what we have learned from the past, through the current research performed in laboratories, to the future of epidemics, we aim at discussing with society. This project will provide visibility and value to the research-and to the researchers-active at the Institute for Research in Biomedicine (IRB) of the Università della Svizzera italiana (USI). In fact, it is from this institution that the project initiates, specifically from DDr. Santiago González, who has been studying the influenza virus for years, a pandemic virus that profoundly changed the history of humankind. Biological notions require however the integration of historical and epidemiological aspects, as well as ethical and social ones. For this reason, such perspectives will be addressed thanks to the competences of medical historian Prof. Bernardino Fantini (University of Geneva) and epidemiologist Prof. Emiliano Albanese (USI), as consultants, and Fondazione Sasso Corbaro, which has been studying ethical clinics and medical humanities for twenty years. L'ideatorio -USI's service of science culture promotion and dialogue between science and society, regional antenna of Science at Cité-is partner of the project and will manage construction, animation and overall project management. Additionally, the city of Bellinzona and the regional tourism board will support the project by offering the prestigious location of Castelgrande, a UNESCO World Heritage castle in Bellinzona and, pending project approval by the SNSF, they will dedicate the 2022 edition of the cultural festival Sconfinare to the topic of contagion.The quality and impact of this project are guaranteed in the first place by IRB's scientific excellence, by the experience of L'ideatorio in the management of science mediation projects and by the support of the city of Bellinzona. Additionally, the project counts on the great affluence of regional, national and international visitors to Castelgrande, the participation of a broad promotional network that includes schools, and the availability of substantial financial means.",,2023,Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice,220187.41,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement,2021 +P28329,199980,"The Tropics. Poverty, forests and diseases.","Tropical forests contain two-thirds of the Earth's terrestrial biodiversity and provide significant benefits through the provision of biological goods, maintenance of genetic diversity, and storage of carbon. Yet the future of the tropics has never been more uncertain. At a time when the world is experiencing unprecedented changes in biodiversity at local and global scales, my research intends to highlight the role tropical forests play in the global ecosystem services. My aim is to investigate the link between two important features of the tropics. First, the role of anthropogenic forest loss and fragmentation in the emergence of infectious and zoonotic diseases. Second, the pervasive poverty which is a persistent socio-economic dimension of the region, existing in majority of the rural communities living in the forest frontiers. These communities have a complex and symbiotic relationship with the environment, often benefiting from them whilst contributing to deforestation. My research specifically aims to understand how the emergence of diseases from deforestation contributes in perpetuating the poverty trap commonly experienced by the rural communities in the tropics. To study this, I will focus on building the poverty-deforestation-disease hypothesis which will explicate how poor households in the forest frontiers engage in low-productivity agriculture for subsistence leading to deforestation. This in turn often has cascading ecological effects by increasing the probability of pathogen spillover due to change in inter-species contact patterns and giving rise to infectious and zoonotic diseases. Emergence of such diseases disproportionately affects the already vulnerable rural communities on the forest margins, pushing them further into poverty and forcing them to continue degrading the natural resource. The focus of my investigation will be the Congo Basin, the second-largest tropical forest cover in the world and where majority of the forest loss is driven by subsistence and small-scale commercial farmers. Additionally, this region is a hotspot for emerging diseases, whose burden has been steadily increasing in recent years. The first part of my research introduces a theoretical model encapsulating the hypothesis and integrating ecological, economic and epidemiological features of the region leading to persistent poverty. The second part will be to empirically investigate the implications for each of the six countries within the Congo Basin, with an initial focus on Ebola and Monkeypox outbreaks and future extensions to other regional tropical diseases. Utilizing spatially disaggregated data with econometric tools, my aim is to establish causal mechanisms and quantify the effect of disease in amplifying the feedback between deforestation and poverty. This can help policymakers in the region to introduce the right incentives and interventions for disease management and poverty reduction while simultaneously achieving tropical conservation goals.",,2023,Aix-Marseille Université École d'économie AMSR UMR 7316 École Centrale Marseille,81508.65,Human Populations | Environment,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Filoviridae | Poxviridae | Novel Pathogen,,,,,,,,,Ebola virus disease | Mpox | Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,"Secondary impacts of disease, response & control measures",Prevention of complications & social sequelae,France,,"Animal and environmental research and research on diseases vectors | Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Economic impacts,2021 +P28331,198607,COVID-19. The social science perspective,"The social sciences analyze the challenges posed by COVID-19 by integrating them into the dynamics of our societies. With the hindsight that characterizes them, these sciences are particularly suited to understanding the social, economic and political dynamics of an illness which, for some, has the characteristics of the devil, and for others, those of a common flu. . This book unpacks how individuals, organizations and communities are coping, suffering and responding to COVID-19.",,2020,Institut de recherches sociologiques Faculté des Sciences de la Société Université de Genève,15821.18,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P28343,216547,Female entrepreneurship during multiple crises: An intersectional perspective on entrepreneurial ecosystems in Switzerland and Colombia,"With this project we seek to examine the ways in which women entrepreneurs in Switzerland and in Colombia have been affected by and have been able to recover from crises such as the COVID-19 pandemic, the most recent economic distortions associated with the war in Ukraine and natural catastrophes such as recent floodings in Barranquilla (Colombia) that were related to climate change. Entrepreneurship is a key dynamic in modern economies (Audretsch et al., 2006) and increasingly entrepreneurial ecosystems (EEs) are understood as essential modes of spatial organizing (Spigel, 2020). Yet, if a large segment of humans (women in this case) is disadvantaged in or even excluded from such ecosystems we risk losing innovative potential. There is an implicit assumption that women entrepreneurs have an equal chance or are treated equally, but this might not be the case in reality (Brush et al., 2019). As a result, policies are often not gender-sensitive (UN Women, 2021). Yet, particularly in crises situation, economic and social policies would need to take differences across gender and other intersectional attributes into account. This is essential for building a more resilient, inclusive, and sustainable society and entrepreneurial ecosystems. In this project, we will examine the ways in which EEs in Switzerland and Colombia provided a supportive environment to entrepreneurs with different intersectional identities to recover from the multi-layered challenges the various crises put on them. Women entrepreneurs with intersectional characteristics such as care duties, migration experience, age, or economic marginalization may face multi-layered challenges to keeping their businesses afloat during crises. We will compare female entrepreneurs with male entrepreneurs as to be able to decipher differences and commonalities in terms of the entrepreneurs` handling of crises situations and the ways entrepreneurial ecosystems provided (or not) a supportive environment that strengthened coping strategies. Understanding the effects of crises on different types of entrepreneurs is crucial to give empirical evidence to policymakers and practitioners who seek to sustain entrepreneurs` livelihoods and support their resilience.Our transatlantic project meets the requirements of the SPIRIT call in multiple ways: Our team consists of two research groups that are headed by female researchers. Combining various intersectional attributes and experiences themselves, we identified common but also differing challenges across our national contexts. In Switzerland and in Colombia we find entrepreneurial ecosystems (Zurich and Barranquilla) that play a central role in the respective national economy and that are affected by recent crises. It is, however, unclear whether and in which ways these EEs are inclusive for women entrepreneurs. Empirical research in other contexts provides evidence that this may not be the case (Motoyama et al., 2021; Neumeyer et al., 2019). Yet, the inclusive character of an EE becomes particularly relevant during crises. For example, women needed to shoulder the brunt of the COVID pandemic because of their care responsibilities during lockdowns (Adams-Prassl et al., 2020) while keeping their businesses running (Grandy et al., 2020). As inclusivity of EEs likely differs across countries, but also in terms of its internal networks as well as its evolutionary stages, evaluating whether context is an asset or liability (Welter, 2011) of entrepreneurship is essential. The research team has a proven track record of promoting an inclusive culture of collaboration. We engage in the spatial social sciences and combine expertise from social and economic geography, economics, and entrepreneurship studies. We will utilize a diversity-oriented recruitment and training program that allows young researchers from the Global North and South to interact with each other. To allow learning from each other, we incorporate research stays for the Colombian-based PhD student in Switzerland and for the Swiss-based PhD student in Colombia. The research team is supported by policy partners in each country, which will ensure the uptake of our findings in the entrepreneurial communities in each context. Results will be published in international peer-reviewed journals. Moreover, we will portray women entrepreneurs in videos that will be created in collaboration with media experts. With policy documents, we aim to inform recovery efforts regarding gender-sensitive policies (e.g. economic, social) to build more resilient, inclusive and sustainable entrepreneurial ecosystems. Our project addresses two societal challenges, namely (i) reducing inequalities and vulnerabilities and (ii) building a more resilient, inclusive, and sustainable society.",,2028,Geographisches Institut Universität Bern,578357.79,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2024 +P28345,196046,Tracking the COVID-19 epidemic in Switzerland: phylogenetics and epidemiological modeling,"Background:In Switzerland, SARS-CoV-2 was first detected in late February, and the COVID-19 epidemic has grown to 10,456 confirmed cases and 145 reported deaths as of 25 March 2020. Across Europe, case numbers and fatalities have been doubling rapidly for several weeks. Alongside the all important patient care by health care professionals, scientists from all over the world have developed mathematical models of COVID-19 transmission and sequenced numerous viral genomes to track the spread and evolution of SARS-CoV-2. During the ongoing COVID-19 pandemic, Nextstrain has developed into the primary platform for real-time analysis of all available SARS-CoV-2 genomes. Sequence submissions from all over the world now paint a detailed phylogeographic picture and clearly show how outbreaks in different parts of the world are related. At the same time, epidemiological modeling efforts have provided essential input for policy makers and anticipated the scale of the outbreak early on. While these two computational approaches have the potential to inform each other, these efforts have been largely disjoint to date.Aims:We aim to integrate genomic epidemiology and epidemiological modeling in order to provide comprehensive inferences and projections for the COVID-19 epidemic in real-time. Specifically, we will apply genomic epidemiology to conduct phylogenetic analysis of SARS-CoV-2 sequence data specifically for Switzerland, apply epidemiological modeling to provide real-time analysis and projections of the COVID-19 epidemic in Switzerland, and expand the Nextstrain platform by an integrated modeling approach where phylogenetic analysis and epidemiological modeling inform each other.Methods:The proposal builds on well-established methodologies from two research teams that have made important contributions to the epidemiological understanding of the COVID-19 pandemic. Phylogenetic techniques are well established in the analysis of viral genomes and Nextstrain has shown how such analyses can be done in real-time. Detailed epidemiological models that are embedded in maximum likelihood and Bayesian frameworks offer great potential for real-time analyses and short-term projections of the spread of emerging infectious diseases.Impact:With continuing spread of SARS-CoV-2 and its consequences for people's health, the economy and the society, it will be critically important that decision makers have a detailed picture of the ongoing epidemiological situation during different phases of the epidemic. The integrated solution for real-time analysis that combines genomic epidemiology with epidemiological modeling within the Nextstrain platform will provide actionable information for decision makers, public health authorities, and for hospital planning. We will be able to track the COVID-19 epidemic across age groups and cantons, and identify transmission chains and links to outbreaks outside of Switzerland.The direct integration with epidemiological models will allow quantification of the phylogenetic information in terms of numbers of infected individuals, or stochasticity of transmission at high spatio-temporal resolution. Such fine-grained analyses and projections will be particularly important when infection control moves from generalized interventions to targeted measures. Finally, the resulting infrastructure will be available for the surveillance and management of other pathogens in the future.",,2023,Institute of Social and Preventive Medicine University of Bern,304233.97,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2020 +P28353,196247,SUSPend: Impact of Social distancing policies and Underreporting on the SPatio-temporal spread of COVID-19,"During infectious disease outbreaks such as the current coronavirus disease (COVID-19) pandemic, modern surveillance systems continuously produce detailed data on reported disease incidence. Typically, these data are available at various geographic resolutions and stratified by age and sex, leading to high-dimensional count time series. Statistical modelling approaches which can handle the heterogeneities and interdependencies in such data are a valuable tool to inform public health decision makers about disease dynamics, to evaluate the effect of intervention measures, and to provide probabilistic forecasts of disease spread. Important factors which need to be taken into account are social contact patterns, mechanisms of geographic spread, and possible underreporting, all of which can vary across regions, age groups, and time. The endemic-epidemic (in the following: EE) framework is an established flexible modelling framework for multivariate infectious disease surveillance counts. A robust, free, and easy-to-use implementation is provided in several R packages. To our knowledge, this is the only readily available implementation of a sophisticated and general model framework for age-stratified spatio-temporal surveillance data. In the past, the EE framework has mainly been used for seasonal diseases, but there is a clear need for general and well-implemented multivariate modelling tools also for acute outbreak situations like the current COVID-19 pandemic. The goal of this project is to extend the EE framework to further improve its applicability in such contexts. Specifically the extensions aim to better address the following aspects:* Assessing the impact of underreporting due to asymptomatic and prodromal carriage and insufficient levels of testing * Determining the role of different age groups and their contact patterns in transmission* Providing impact estimates of control and mitigation strategies such as travel restriction and other social distancing policiesThis project will provide evidence to improve public health response and aid in decisions on optimal social control strategies, particularly when to initiate travel restrictions and social distancing measures, and improve situational awareness.",,2022,Gesundheitswissendchaften und Medizin Prävention Universität Luzern,184687.92,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P28365,222318,Redistributive Effects of Monetary Conditions on Housing Credit Since Banking Deregulation,"Overall objectives and specific aims: Homeownership is a policy goal in the US. On one hand, income inequality has been widening since the 1990s. On the other hand, banking branch deregulation, starting in the mid-1990s, resulted in increased mortgage supply by lowering inter-state geographical barriers. A natural question is how much gains in expanded mortgage supply have accrued to lower-income households. Further, credit supply responds to monetary conditions. Interest rates have been (mostly) falling since the deregulation, and esp. since the Great Financial Crisis. This raises the question of how monetary conditions affect credit supply across different income groups. This study investigates how monetary conditions influence mortgage lending for households with varying income levels in the US. In addition, how has this relationship changed since the financial crisis? How did the reforms introduced by the Dodd Frank Act in 2011 interact with monetary conditions to affect housing finance? How did the COVID-19 pandemic impact housing finance across income groups? The findings aim to guide policymakers in promoting equitable housing finance practices.Background and rationale: The existing research indicates that expansionary monetary policy can benefit low-income households in the short and medium term. However, there's a lack of empirical investigation into the long-term redistribution effects of monetary conditions, as they're often considered neutral over time. This study aims to bridge this gap by examining the redistributive effects of monetary conditions on mortgage credit allocation to households over an extended period, 1995-2021. Through this analysis, the research aims to shed light on potential redistributive outcomes of such policies and their implications for various income groups in the housing market.Methods: Our empirical strategy is based on the notion that local incomes tend to be correlated with local economic/housing conditions. We will utilize publicly available mortgage data from the Home Mortgage Disclosure Act (HMDA). The HMDA (panel) data provides valuable information at the census tract level, which aligns with the granularity of local income data available from a federal agency, the Department of Housing and Urban Development (HUD). Data on other control variables such as house price index, interest rates, and cost of intermediation are also widely publicly available. We will employ fixed-effect panel data regression methodology. We will regress mortgage credit on the interaction of interest rate and income at census tract level, while controlling for local-economic conditions and lender, year, and geographic fixed effects. An insignificant coefficient on the interaction term indicates income-neutrality, while a negative coefficient suggests regressive monetary conditions, impacting lower-income households more than higher-income ones.Expected results: We expect a publication in leading economics, finance, and banking journals, alongside presenting at renowned conferences like AEA, AFA, EEA, and EFA. Our outreach will extend to social media to engage a wider audience. Our findings will contribute comprehensive insights into the influence of monetary policy on income inequality in the housing market. Unlike short-term studies, our long-term analysis addresses the broader role of monetary policy in redistributive outcomes. Impact: Income inequality is a complex and slowly evolving variable that takes time to manifest its effects on long-term consumption. By examining the long-term dynamics of income inequality in relation to housing finance and monetary policy, our research has the potential to inform policymakers about the long-term implications of monetary policy decisions on income distribution and inequality, contributing to more equitable policymaking.",,2024,Institut für Banking und Finance Universität Zürich,11137.69,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2024 +P28377,215863,"Bridging the gap: Dialogues between scientists and the public, policymakers, and journalists about lost past pandemic experiences","Since COVID-19, interest in past pandemics has been greater than ever because lessons from history can contribute to a better understanding of the present. However, COVID-19 has revealed a flagrant memory gap about pandemics: Switzerland has lost its ""collective memory"" of 20th century epidemics. The experiences of past epidemics have been forgotten, only fragmentarily researched, and existing knowledge is poorly communicated to the public at large and among policymakers. To fill this gap, the project team has intensively studied past pandemics in Switzerland (e.g., 1890, 1918, 1957). We aim to provide evidence-based knowledge from the past in view of a future pandemic. Our publications resulting from these research projects have received considerable national and international attention. Since 2022, the four Agora applicants have been working on a pilot and outreach project called LEAD (funded by the DIZH). We are developing a publicly accessible dissemination hub that provides open research data as well as selective data stories from past pandemics in Switzerland. Using personas, we have defined and described the public, policymakers, and journalists as target groups. The LEAD project will be completed in March 2023. Thus far, efforts to communicate our findings have been more digitally focused. Our next step is to build on the publications/projects and the LEAD hub. Further, we will initiate a more direct dialogue between researchers and target groups. The goal of the proposed Agora project is to create a multi-way communication approach that seeks to establish a dialogue between us researchers on the one hand, and policymakers, media professionals, and the public on the other. Our communication approach consists of three pillars: 1) Biographical and journalistic interviews with contemporary witnesses (or their descendants), recorded as videos and then integrated in multimedia stories. These will be included in LEAD to bring to life personal experiences from the 1918 and 1957 pandemics and, indirectly, from descendants (based on family diaries and biographical dossiers in archives). Here, the internationally known artist and project partner Mats Staub will guide us in conducting such biographical video conversations. 2) Workshops with policymakers. Here we will mobilize and expand our broad network in the field of public health. We will organize two workshops aimed at involving policymakers, politicians, and federal/cantonal/local authorities from all language regions, and raising awareness of the valuable lessons learned from the past (of pandemics, and beyond). Above all, dialogue with policymakers will help us optimize the transfer of knowledge to this target group. This part of the project is supported by our project partner, Reatch (a think tank specialized in science-policy dialogue). 3) Outreach events in the last months of the project: Here, we will hold three high-profile public two-hour events to deepen dialogue with our target audiences about past pandemic experiences and their value. These events will include expert panel discussions, personal experiences (from Pillar 1), and a small exhibition. These events will take place at the Tonhalle Zürich (which was an emergency flu hospital in 1918), at the ZHAW JournalismusTag, and the Swiss Public Health Conference. Overall, the project will help fill the memory gap of past pandemics in Switzerland, by reaching a considerable number of people from different relevant target groups through different means of communication. Since we will also be showing how past experiences have been forgotten during previous pandemics, this project will provide additional rationale as to not ignore or forget learned experiences from the COVID-19 pandemic in the future. We are convinced that our efforts will create awareness among target audiences that these past experiences are now researched, disseminated, and valuable, especially if a new pandemic emerges and the need for historical contextualization reemerges.",,2025,Institut für Evolutionäre Medizin IEM Medizinische Fakultät Universität Zürich,225567.11,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2023 +P28390,207663,"Towards the viable supply chain: Managing targets across efficiency, resilience, and sustainability","Swiss companies that want to remain globally competitive are caught in a multi-layered tension between efficiency, resilience, and sustainability. Megatrends such as climate change and resource scarcity, as well as the resulting disruptions that affect both the global and Swiss economies, necessitate a holistic view to think long-term while at the same time being prepared for unexpected events that occur in the short term. The efficiency-focused paradigm is no longer a blind recipe for success. Lean supply chains can incur enormous costs in a short time if disruption happen at some point in the chain. The targets of the efficiency paradigm clash against the requirements of resilience and sustainability in the supply chain. Recent research shows that the simultaneous consideration of resilience, sustainability and efficiency is essential to achieve 'Supply Chain Viability' (SCV) (Hofmann and Langner 2020). To study and elaborate such SCV, it is a crucial element to ensure the integral consideration of all three objectives to achieve it.The goal of this research project is to develop a concept of SCV that incorporates resilience, efficiency, and sustainability into the overall consideration. Therefore, the research project is divided in two sections: First, the scientific work on supply chain viability. This section consists of three work packages (WP) and the major deliverable will be a model to measure and verify the supply chain viability on a industry sector or company granularity. Second, the practical aspect consisting of two WPs. In the end of this section, the major deliverable will be a management guideline for practitioners to successfully improve SCV through precise projects embedded in a holistic context. In addition, the proposal addresses the need to develop resilient, sustainable supply chains in the context of current COVID-19 pandemic disruptions (Choi, Rogers et al. 2020) and long-term climate change challenges (Azadegan and Dooley 2021). This research addresses the need to balance efficiency, resilience, and sustainability in supply chain management (SCM), and from this, shape a new, contemporary paradigm for SCM (Wieland, Handfield et al. 2016, Liu, Zhu et al. 2020). This new paradigm allows executives to improve their business in the form of a management guide. In pursuit of this goal, the research team, including Erik Hofmann (grant applicant), Daniel Langner, Laurin Zemmrich (University of St.Gallen, Switzerland), and the project partners Thomas Choi (Arizona State University, USA), Alexandre Dolgui (IMT Atlantique, France), and Donna Marshall (University College Dublin, Ireland) aims to answer five guiding research questions:RQ1: What concept aligns efficiency, resilience, and sustainability in supply chain management? RQ2: What are the critical conflicting or aligned targets of resilience, sustainability, and efficiency and their interdependence in terms of supply chain viability?RQ3: How can supply chain viability be modelled and operationalized?RQ4: How can purpose setting contribute to achieve a higher level of supply chain viability?RQ5: What are practical pathways to implement supply chain viability?The research team intends to follow a design science research approach that includes relevance, rigor, and design cycles. Within the WPs, the team will use a variety of methods, including survey research, expert interviews, Delphi studies, and literature reviews to develop theoretical and managerial contributions. In the evaluative phases of the research, the team will rely on expert interviews. The results of the research project will be published in leading peer-reviewed journals and will be presented on high ranked international conferences.",,2023,Institut für Supply Chain Management (ISCM) Universität St. Gallen,401101.68,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P28413,214084,Between Expectation and Empathy: Expertise negotiation and practices of understanding in online scholarly communication,"According to studies to date, the Covid19 pandemic has not yet led to a decline in confidence in the problem-solving competence of science in Germany. Nevertheless, there is much public discussion in Germany about the performance of scientific expertise in societal crises - the tone has intensified, society is perceived as polarised, and conflicts appear unsolvable. The facilitation of successful understanding of social problems for which scientific expertise is needed is therefore becoming increasingly important - and this is especially true across different interests, knowledge resources and socialisations. Be it in a fundamental sense with regard to social peace in our democracy, be it concretely with regard to the necessary joint efforts to solve current political challenges.Many scientists are therefore becoming increasingly involved in the public debate, for example through science blogs, which make it possible in a special way to exchange ideas with interested parties and to allow citizens with different levels of prior knowledge to participate in the discourse. Comments and responses to blogposts by scientists and science journalists, such as those available in abundance and thematic breadth on the portal SciLogs (since 2000, operated by Spektrum-Verlag), show that there are constant and by no means only factually conducted processes of negotiating expertise. Conflicts arise especially in the face of different expectations of professional roles and associated communicative practices, but also of understanding and insight on the part of lay participants. In this context, the initiating blog post seems to be partly responsible for the heatedness of debates and the success/failure of understanding, not only because of the content, but also because of the linguistic and multimedia way of dealing with the topic.This is where the corpus and discourse linguistic project comes in by setting goals on three levels: Goal 1 is the linguistic operationalisation of empathy in systematic connection with the concept of expectation and reciprocal expectation. This is done in the course of a sociopragmatic in-depth analysis of practices of understanding that serve to negotiate expertise in the comment section of science blogs. By operationalisation, we mean both the theory-guided, deductive formation of categories and their inductive differentiation as well as the direct methodological application, such as the systematic recording of indicators of empathic practices for qualitative text annotation and corpus linguistic detection. This goal is pursued in order to make the dynamics between blogposts, comments and responses systematically describable and to be able to linguistically typify communicative practices of expertise and empathy- and expectation-related understanding.Goal 2 comprises validation and generalisation: The viability of the categories and indicators developed on the basis of hypotheses and corpus (Goal 1) is to be examined and, with a view to the exemplary nature of expertise and communication practices, tested in an explorative and data-driven manner with regard to transferability to other communicative and thematic contexts. In this target area, therefore, a methodological continuation will be carried out, which at the same time should contribute to reconfiguration and further development at the level of theory building. In this way, both the blog-specificity of the practices of understanding and possible blind spots in the system of categories and indicators can be worked out.Aim 3 is a discourse-linguistic and thus a content-application-oriented one: the section of SciLogs texts that can be understood as part of the climate change discourse and which is estimated to account for about one sixth of the total corpus of 229,328 entries as a whole is to be subjected to a diachronic comparative analysis (2000-2019 vs. 2020-2023). The aim is to gain insights into the dynamics and change of practices of understanding under the transformational influence of social crises such as the Covid19 pandemic. The question to be asked here is to what extent discourses and discourse entanglements have an effect on themselves and whether and how attribution criteria and relevance perceptions of expertise change as a result.The focus is thus on the qualitative and quantitative reconstruction of communicative practices and linguistic patterns that are crucial for successful online science communication or that stand in the way of it because they contribute to or disrupt understanding in the course of negotiating, confirming and validating expertise. Methodologically, the concepts of empathy and expectation are central. Using the example of climate change discourse, we will also examine how such media-mediated communication practices are currently changing as a result of the pandemic and whether and how a possible dynamic in the quality of communication can be measured on a corpus linguistic basis.",,2026,Department of German and Scandinavian Studies University of Zurich,231942.04,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2023 +P28418,218018,Digital early detection of psychological disorder after the loss of a loved one: DeathGRIP (Grief Response in Post Pandemic Society),"The mental health field is at a tipping point. As the world adjusts to COVID-19, there is an urgent need to prepare for a 'shadow' pandemic of mental health disorders such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Simultaneously, the recent introduction of a new mental health disorder, prolonged grief disorder (PGD), in the eleventh edition of the International Classification of Disorders (ICD-11) and Diagnostic Statistical Manual 5th edition (DSM 5-TR) is both an opportunity and a serious challenge. The inclusion legitimizes a long-known mental health challenge and thus creates an opportunity to provide those suffering from prolonged grief with the right care at the right time. At the same time, researchers and clinicians are faced with the challenge of filling substantial research and clinical knowledge gaps. Currently, lack of knowledge about the illness course of PGD, symptom structure and predictors of illness severity are contributing to a crisis of missed diagnosis, long term chronic care needs and increased burden on care systems.This project will use experience sampling methodology to give longitudinal, fine-grained data on the sequalae of psychological disorder after bereavement; the first investigation to do so. Three studies are proposed: (1) Longitudinal digital experience sampling methodology (ESM) on the psychological impact of bereavement in Switzerland; (2) Mapping of digital markers of PGD in Iran, Kenya, and China: Cross cultural cohort comparison study; and (3) Digital First Response for humanitarian migrants: early detection and alerting of psychological disorder using personalized ESM. The global recognition of PGD is an opportunity to unite clinicians and researchers with a systematic, evidence based and multi-levelled response. The main aim of this project is to provide a digital early detection system for PGD and its psychological sequalae so that chronic and debilitating outcomes may be circumvented for individuals and health care systems. These would be the first studies in the field to 1) examine psychological sequalae of bereavement using longitudinal and ESM mobile app methodology (study 1), 2) examine the onset and course of multiple disorders (PGD, PTSD, MDD) following bereavement (study 1), 3) include fine grained analysis of symptoms within and between cultural groups (study 2), and 4) develop an early detection system for a high-risk group of humanitarian migrants (study 3). In our post-pandemic society, evidence-based clinical guidance on the course, etiology and risk factors after bereavement are urgently needed.",,2029,Centre for Research and Development Interkantonale Hochschule für Heilpädagogik,1873808.21,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P28423,191891,Precision epidemiology,"Phylogenetic trees can be used to denote how pathogens isolated from different patients are related. This has proven to be an important tool to study the spread of diseases.Such phylogenetic trees can be reconstructed from genetic sequence data from pathogens by making use of the fact that pathogens isolated from patients further apart in the transmission history have genetic sequences with more nucleotide differences. Additionally, past population dynamics can be reconstructed from such phylogenetic trees by using phylodynamic methods. These approaches have been used to study the spread of various diseases, such as the 2009 influenza A/H1N1 pandemic, the 2014/15 Ebola outbreak in western Africa, ZIKA viruses in South America or MERS coronavirus in Saudi Arabia.In order to extract transmission patterns from phylogenetic trees, the shared evolutionary history of pathogens isolated from hosts has to actually be tree like. Recombination processes, however, cause this shared evolutionary history to be a network and not just a tree. Recombination processes can cause lineages to carry the genetic information of more than just one ancestral lineages. In order to study such processes, methods that are able to infer recombination networks (and not just trees) are required.One of these recombination process is called reassortment, where segments of segmented viruses are re-shuffled upon a co-infection event. In a recently introduced method, we showed that we are indeed able to infer such networks from full genomic sequences of human influenza viruses. This allowed us to infer where and when reassortment events occurred while properly accounting for uncertainty in the data and to show that lineages that persist for longer tend to have more such events. However, there remains a lot unknown about what are the determining factors that make reassortment events successful. In the first part of this research project, I will elucidate the factors that make reassortment events successful or not by studying the fitness effects of these events from reassortment networks of human influenza viruses.While existing for reassortment, inferring recombination networks remains challenging for other genetic recombination events. One of the most prevalent of those is homologous recombination.In the second part of this research project, I will extend the current Markov chain Monte Carlo approach to infer reassortment networks to allow for homologous recombination. This will allows us to study recombination processes across different pathogens. Additionally, it will allows of to perform phylogenetic and phylodynamic inferences for pathogens that recombine using full genomes. This in turn will greatly increase our ability to elucidate how pathogens spread.",,2021,Prlic Laboratory Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center,79794.15,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P28427,191749,"Governing pathogen- and benefit-sharing: From pandemic influenza to Ebola, Zika and MERS","Rapid, reliable sharing of pathogens among public health authorities and research institutions is critical for identifying a disease, assessing risk, and developing strategies and technologies to control outbreaks. However, periodic cases of delayed sharing of pathogens have punctuated the last decade, where, in some cases, delayed sharing has been justified politically by citing concerns with access and benefit and legally by referring to the UN Convention on Biological Diversity's (CBD) principle of sovereignty over genetic resources. Such cases have underlined how pathogen-sharing needs to go in parallel with fair access to outbreak-control technologies and other benefits resulting from pathogen samples. The overall objective of the workshop is to allow participants from sending and receiving laboratories, research and academic institutions and stakeholders from governmental, inter-governmental and non-governmental sectors to present and discuss, in the form of roundtables, the issue of pathogen- and benefit-sharing and develop a way forward. As such, this workshop has the following specific aims, to:1-Explore the scientific factors, organizational policies, formal and informal norms and economic considerations driving pathogen and benefit sharing 2-Assess existing global legal and governance frameworks on pathogen- and benefit- sharing and explore the possibility of tools, instruments and frameworks tailored to emerging infectious diseases (e.g. Zika, MERS, Ebola)As such, the workshop will explore the most important determinants (legal, economic, political, scientific, technological, social) of pathogen and benefit sharing, assess the existing knowledge gaps and examine progress that can be made to rectify them. Furthermore, the workshop will discuss the benefits and shortcomings of existing global governance frameworks for pathogen-sharing and explore the specific global governance tools, instruments and frameworks that are likely be most effective. By translating these considerations into legal and policy terms, we expect the workshop will start a conversation that will lead to laying the ground for further research in this area.",,2020,Global Health Centre Graduate Institute,13511.79,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Filoviridae | Flaviviridae | Novel Pathogen,,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Zika virus disease | Congenital Zika virus disease | Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Policies for public health, disease control & community resilience",Policy research and interventions,2020 +P28433,205097,Human immune dysregulation in viral defense,"Persistent, recurrent, life-threatening or fatal viral infections in neonates, infants and toddlers with inborn errors of immunity sadly exemplify the importance of certain gene products in protecting the body from these infectious agents. Some of these inborn diseases are characterized by immune dysregulation as well as susceptibility to (or poor control of) viral infections. We hypothesize that pediatric patients with severe inflammatory complications temporally associated with viral infections bear monogenic inborn errors of immunity. We aim to discover novel inborn errors of immunity underlying these multisystem inflammatory syndromes (MIS) triggered by viral infections and we aim to characterize the novel gene variants on a molecular, cellular and systemic level.Our preparatory work for the present application is strong, as we have established a workflow, which has already been successful in discovering and characterizing inborn errors of immunity with MIS and we have already included more than 50 pediatric patients in our study with very severe or lethal multisystem inflammatory complications temporally associated with viral infections. We have performed whole exome sequencing in all these study participants, including their parents and healthy siblings. This severe disease entity is rare. Nevertheless, we expect to include another 15 patients in our study, during the course of the herein proposed project, thanks to international collaborations and thanks to our role as a national reference laboratory for these diseases. Importantly, we have already discovered very rare, damaging variants in genes hitherto not known to be implicated in immune regulation which shall be further characterized during the course of the present project.To discover novel inborn errors of immunity, we are applying genome-wide association approaches. Once we have shown the deleteriousness of the mutant allele(s) and the link between the genotype and the cell phenotype, we aim to investigate the mechanism of inflammation by studying (a) patients' serum and cells, (b) cells that recapitulate the patient's genotype and/or (c) murine models that recapitulate the patient's genotype and phenotype. We will determine (i) whether these candidate genes are linked to previously reported MIS-disease-causing genes, and (ii) how they operate in either of the two cell types that are crucial for immune regulation in the context of a viral infection, i.e. cytotoxic lymphocytes and/or target cells (antigen-presenting cells and/or infected cells). On the cellular level, our hypothesis is that MIS is either caused by a lymphocyte-intrinsic defect and/or defect of the antigen-presenting or infected cell, since the latter has an intrinsic or adopted increase in killing resistance or a dysregulation in innate defense mechanisms. Our in-depth, experiment-based, mechanistic studies shall prove the relevance of the gene products as important immune system's components for human immune regulation during viral defense. This will pave the way for personalized therapies in life-threatening severe inflammatory conditions according to causally tested links between the molecular underpinnings and the cellular behaviors characterizing a disease. Our study shall result in breakthrough discoveries in the field of multisystem inflammatory complications triggered by viral infections. Furthermore, the results will also shed light on the pathogenesis of more common inflammatory complications triggered by viral infections, such as in the setting of COVID-19, which contribute to the global burden of disease and death..",,2024,"Abteilung für Immunologie, Hämatologie, Onkologie, Infektiologie Universitäts-Kinderkliniken",515764.52,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2022 +P28443,196538,COWWID-19 | Surveillance of SARS-CoV-2 in Wastewater - an Early Warning System to Track the Spatio-temporal Development of COVID-19,"Imagine we could i) screen effectively thousands of people for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) simultaneously, ii) detect the outbreak before people with symptoms present at hospitals, and iii) track the spatio-temporal dynamics in real-time. The quantification of the SARS-CoV-2 load in wastewater enables such an opportunity: a single routine wastewater sample encompasses viruses shed in an entire wastewater treatment plant's (WWTP) catchment, and includes viruses excreted by infected individuals well before they are clinically diagnosed. Recognizing the unique potential of wastewater-based epidemiology (WBE) to serve as an early warning tool, we rapid-ly assembled an interdisciplinary team and started daily wastewater sample collection on 28 February in the affected areas Ticino, Vaud and Zurich (12 WWTPs covering a population of 737'000 people). Based on our team's experience in environmental virology, we anticipate detecting a SARS-CoV-2 signal in raw wastewater from as few as 10 infected indi-viduals. Our ultimate objective is to establish a WBE tool to track the current and future disease outbreaks in close to real-time. A WBE early warning system would allow public health institutions and decision makers to gain valuable time to assess the 'true' extent of an outbreak and react to its dynamics. This will facilitate adapting and enforcing mitigation measures, and ultimately save lives. Our specific goals (G) are:G1: Detect - Early detection and continued monitoring of outbreak. The reliable and rapid detection of SARS-CoV-2 in wastewater is instrumental to implementing a WBE approach to detect an outbreak early. We will optimize and apply a method to concentrate wastewater samples and quantify the concentration of SARS-CoV-2 with a turnaround time of 10 hours from sampling to result. With accompanying chemical analyses we will provide a second, indirect tool to esti-mate the outbreak dynamics, by measuring the medical intervention of the population. Selected wastewater samples will be screened for medication like antiretroviral drugs that may be used and co-occur with the COVID-19 diagnosis. G2: Model - Estimate outbreak curve and effect of mitigation measures. SARS-CoV-2 loading in raw wastewater pro-vides a quantitative indicator of the number of people actively shedding the virus in feces. Time series data on loading will be used to track the outbreak curve, preceding clinical case confirmation data by up to two weeks. Through analysis of the trajectory of loading rates, we will inform the true COVID-19 epidemic curve, including magnitude of the out-break, timing of outbreak stabilization, and - crucially - real-time feedback on intervention effectiveness.G3: Implement - Suggest design for future early warning system. Routine samples from selected WWTPs should be available for collection and analyses at any time. Aiming for a substantial population size and a good geographical distri-bution of WWTPs, a future emergency wastewater surveillance network in Switzerland could consist of 19 WWTPs covering 2.5 million people (30% of the population). The number and strategic selection of WWTPs can be extended depending on testing capacity. Our approach is not limited to COVID-19 and can readily be adapted to include notifiable seasonal viruses (e.g., influen-za) or future pandemic viruses. The relevance of this work thus goes beyond the current COVID-19 crisis.",,2021,"Strategic Environmental Sanitation Planning Department Sanitation, Water and Solid Waste Eawag",188256.52,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics | Disease surveillance & mapping,2020 +P28444,209973,"Frontline work in humanitarian disasters: Bridging state and non-state rationalities towards region-based, multi-layered crisis management","Our research project focuses on the ""ad-hoc multilevel doing, deciding and cooperating"" of state and non-state frontline work that emerged in reaction to the COVID-19 pandemic. It is estimated that between 1 and 1.7 million people in Switzerland were reliant on aid - either in the form of financial assistance, food aid, or other basic support. Most of such aid was provided by humanitarian organisations, foundations and churches, as well as private individuals working at the frontline. Consequently, these frontline workers implemented policies at the local level and filled gaps that state authorities could not or would not cover. We propose a multi-level governance approach that considers the variety of actors and their organisational rationalities to understand how they overcame organisational routines, built common procedures and, in some cases, reinterpreted the given legal framework. Due to its federal organisation and the response to COVID-19 on a national scale, in Switzerland this happens at the local and regional level. Moreover, we analyse such practices in the broader theoretical context of street level bureaucracy. Thus, we contribute to the deconstruction of the centrality of the state and argue that government research needs to consider non-governmental and private actors, acting on the frontline, that often function as the prolonged arm of the state.Our research is guided by two main sets of questions: (1) How did (non) state frontline work react to the (new) precarities that individuals faced due to the COVID-19 pandemic? What effects did the disruption in supporting people in need have on such actors? (2) Which groups were neglect-ed by state-funded support during the pandemic? How were these groups supported by alternatives? Which actors became visible in these support networks?Throughout our project we are pursuing three overall objectives: (1) To identify the people who have not been adequately reached in the current crisis and clarify how their inclusion can be en-sured now and in any coming crisis. (2) To generate evidence-based knowledge for state and non-state decision-makers to be able to comprehensively respond to potential future crises by developing a crisis management approach. (3) To establish a field of action and professional practice around 'Frontline Work' to understand policy implementation, state practices and the work of governments in relation to non-state actors.Our project is supported by the five most important humanitarian organisations in Switzerland, the two most important national free food distributors, Swiss Solidarity, a foundation that granted more than 43 million Swiss francs from the private sector during the national lockdown in support of frontline work organisations, and many local and regional frontline work organisations that have been working with affected people since the beginning of the pandemic, as well as the social welfare services of the cities of Lausanne, Basel, and Lugano - the three regions in which we conduct our in-depth case study. Our data collection consists of document analysis and reconstructive interviews across Switzerland and within the cantons of our case studies, as well as focus group discussions with frontline workers allowing us to draw on the data of such meetings, but also to validate our preliminary findings throughout the project and developing a prototype for future crisis management. The expected results are not only published in peer-reviewed scientific and professional oriented publications, but also in a policy brief together with process-oriented results that are further developed by practitioners (e.g., out of the focus group discussions).",,2026,Institut Sozialplanung u. Stadtentwicklung Hochschule für Soziale Arbeit Fachhochschule Nordwestschweiz,528907.94,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Social impacts | Other secondary impacts | Health leadership and governance,2023 +P28445,198290,Implementation of a crystallographic fragment screening pipeline to advance preclinical drug discovery efforts toward the development of COVID-19 antivirals,"Despite the ever-present possibility of a global viral pandemic, the world was caught off guard by the sudden appearance and rapid spread of SARS-CoV-2. Given the virulence and infectivity of the virus, an immediate global response is required to meet the current and any future coronavirus pandemics. While classical vaccinations are perhaps the ideal form of intervention, they are not always sufficient to deliver long term protection. Small molecular drugs targeting multiple non-structural proteins (NSPs), however, have already been proven to be efficient treatments in the case of RNA viruses such as HCV, but there are no effective treatments for coronaviruses currently available. Therefore, development of multi-target small molecule drugs is needed to combat current, recurring and future CoVs. Although the development cycle for small molecule drug discovery is relatively long (5-15 years), recent advances in high-throughput crystallography could expedite the structure-guided drive to lead compounds and high-affinity drug-like inhibitors. The power of HT crystallography has been convincedly demonstrated by the very recent international efforts in structure determinations of NSPs of SARS-CoV-2. X-ray structures of nine of 15 NSPs have been solved and ~100 fragment-bound main proteinase structures have determined in just a few months. However, the structure of the RNA-helicase (NSP13) - a central component of the viral replication organelle that is essential for RNA synthesis remains elusive, probably because of its multi-domain architecture. The main applicants have been working for years in the structural and functional study of helicases. We determined the very first CoV RNA helicase structure - MERS-CoV NSP13 - in 2017, and three more RNA helicase structures from other RNA viruses in the following years. Since the outbreak of Covid-19, we have naturally geared our research effort towards SARS-CoV-2 RNA helicase, aiming to make a unique contribution to the international efforts in developing multi-target drugs against SARS-CoV-2.This proposal aims to reveal novel binding sites in multiple enzymatic states of NSP13 by a multi-channel approach that is designed to utilize macromolecular crystallography methods both at cryogenic and room-temperatures. The first of these channels is to determine high-resolution X-ray structures of NSP13 in various enzymatic states. The second channel is to assess, through biophysics and X-ray crystallography, if any currently available inhibitors also inhibit SARS-CoV-2. The third channel is to attempt to discover novel molecular entities with anti-viral properties. Fragment-screening, both under cryo (100 K) and at more physiological temperatures (293 K), has the potential to explore comprehensively the molecular space for both direct and allosteric inhibition of NSP13 in different conformational states. The information gained from these three channels will feed into one another, for example an understanding of inhibitor binding can aid the stabilization of other enzymatic states, or fragment binding data can inform the improvement of existing inhibitors.To tackle this ambitious project, we have assembled a unique team with broad expertise from structural virology to advanced macromolecular crystallography. The key to the success of this proposal is fast and regular access to large scale X-ray crystallographic infrastructure, and the Paul Scherrer Institut is ideally placed to carry out the central aspects of the proposed research. Given the similarity of coronaviruses, the technologies and methods developed in this proposal will facilitate and expedite a response to any future pandemic.",,2023,Laboratory for Macromolecules and Bioimaging Photon Science Division Paul Scherrer Institut,252505.63,Viruses | Other,Not applicable,Not Applicable,Not applicable,,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2020 +P28449,196239,"Tracking and Managing Economic and Social Impact of COVID-19 through Collective Emotions, Media Traces, and Satellite-Based Remote Sensing Data","This twenty-four month research project uses media trace and satellite-based remote sensing data to examine and manage the economic and social impact of collective emotions, emotional contagions, and pandemic-induced fear during the COVID-19 pandemic. It further provides policy makers, health care officials, and disaster mitigation workers with a global early warning system that synthesizes media trace data and satellite-based remote sensing data into an open-access online platform. In doing so, it answers the SNSF proposal call to examine the societal impact of COVID-19 at large; understand and combat misinformation, stigma, and fear; examine the impact of official and social media communications; and support global coordination and crisis management. Our research team has taken the lead in our field in the use of highly technical data sources and methods to estimate and manage the economic and social impacts of COVID-19 and other natural threats. Our use of media trace data and satellite-based remote sensing data for COVID-19 research has twice been featured in MIT Sloan Management Review. Our research leverages an in-house platform with information on over a quarter of a billion news articles, along with custom code for analyzing satellite-based remote sensing data, to accelerate time to delivery and mitigate project risk. As a result, all of the proposed deliverables are low-risk and will be delivered within twenty-four months from the start of the project. This research project consists of three work packages (WP). WP1 examines how official COVID-19 mitigation guidance influenced company and organization compliance through the lens of collective emotions and pandemic-induced fear. More precisely, we investigate how message framing and campaign dissemination channels impacted organizational support for official COVID-19 mitigation efforts. In doing so, we try to determine how authorities can manage future pandemic related communication. WP2 examines the economic and social impact of collective emotions and emotional contagions during the COVID-19 pandemic through the use of satellite-based remote sensing data. We expect to see that observed differences in cross-regional and cross-national COVID-19 mitigation compliance are partially attributable to emotional contagions. WP3 delivers an online global early warning platform to identify and track the progress of COVID-19 and future epidemics near real-time. WP3 will be prioritized, and we will deliver a pilot by the end of 2020. This project is led by Prof. Dr. Charlotta Sirén from the University of St.Gallen, who is joined by Prof. Dr. Joakim Wincent, Prof. Dr. Dietmar Grichnik, and Michael Hudecheck from the University of St.Gallen. The main international project partner is Prof. Dr. Gerard George from Singapore Management University. The members of our research team have several decades of combined experience and an outstanding track record of publishing in leading academic journals. The research project will fund one Ph.D. candidate (100%), one Post Doc. (50%), and associated analytical equipment and infrastructure. The total budget for the project is CHF 280.745.",,2023,Universität St. Gallen,322115.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P28455,199256,Augmenting PGE2 as a Novel Strategy to Treat Ventilator-Induced Diaphragmatic Dysfunction (VIDD),"Background and Rationale: Though the ongoing COVID-19 pandemic affects all age groups, elderly patients (over 75) are much more likely to require mechanical ventilation (MV) upon contracting COVID-19. MV support can lead to progressive and often deadly diaphragmatic muscle atrophy and contractile dysfunction referred to as ventilator-induced diaphragmatic dysfunction (VIDD). VIDD risk increases proportionally to time spent on MV, and COVID-19 patients, who spend weeks to months on a ventilator, are therefore at particularly high risk. Currently there are no effective treatments for COVID-19-associated VIDD. During my SNF Early Postdoc.mobility fellowship, I discovered that short term treatment of skeletal muscle stem cells with the eicosanoid PGE2 enhances their long-term regenerative potential via epigenetic mechanisms. Normally, upon injury, elevated PGE2 signals via the EP4 receptor to augment the function of muscle stem cells (MuSCs) to repair injured myofibers. PGE2 is degraded by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), can be inhibited by the small molecule noncompetitive inhibitor SW033291 (SW). Aged muscle expresses higher concentrations of 15-PGDH and consequently significantly lower levels of PGE2 than young muscle. We found that a systemic decrease in 15-PGDH activity via SW treatment increases PGE2 levels, attenuates skeletal muscle atrophy, and augments limb muscle strength in aged mice (Palla, Ravichandran, et al., Science, Accepted for publication with minor revisions). Diaphragm muscle is replete with MuSCs and express the PGE2 receptor, EP4, and the PGE2 degrading enzyme,15-PGDH, the target of SW. These data motivate my hypothesis that using SW to boost PGE2 levels in the diaphragm will augment the regenerative function of diaphragm MuSCs, rescue atrophy, and rebuild strength allowing COVID-19 survivors to surmount VIDD. Our preliminary data suggest that this approach will be particularly effective for the elderly.Objectives and Specific Aims: Although limb muscle MuSCs have been extensively characterized, studies of diaphragm MuSCs in mouse and human are lacking. My objective is to establish 15-PGDH inhibition as a therapeutic strategy to stimulate diaphragm regeneration and strength. My specific aims are to 1) demonstrate that PGE2 augments the proliferation and regenerative function of human diaphragm-derived muscle stem cells; 2) show that increasing PGE2 levels via 15-PGDH inhibition enhances strength and reduces diaphragm muscle atrophy via (i) augmenting MuSC proliferation and function and (ii) promoting hypertrophy and improving strength of mature myofibers; and 3) characterize the downstream mechanisms of PG2/EP4 mediated of atrophy and strength.Methods: This proposal represents an ongoing collaboration between the labs of Helen Blau, PhD, and Joseph Shrager, MD, both faculty at Stanford University. For my studies, I will obtain human diaphragm biopsies from our collaborator, Dr. Shrager, a cardiothoracic surgeon. To establish if PGE2 augments the regeneration and function of diaphragm MuSCs, I will transiently expose human diaphragm MuSCs isolated from biopsies from young (under 40) and elderly (over 70) patients to PGE2 and carry out assays of proliferation and function using (1) time-lapse imaging to track muscle stem cell proliferation, death and changes in cell fate, (2) non-invasive bioluminescence imaging assays to monitor the engraftment of these human diaphragm MuSCs in vivo into immunodeficient mice (3) non-invasive in vivo force measurements to assess muscle strength post-transplant. In addition to human diaphragm studies, I will employ a well-established 'Rodent ICU' model of VIDD using Fischer F344/BN hybrid rats (male and female; aged 4-6 months for young and >2 years for aged). The effect of SW on rescuing diaphragm atrophy will be measured by quantifying the diaphragm isometric specific contractile force in conjunction with histology. Molecular biology and biochemical assays (qPCR, immunohistochemistry, western blotting) will be employed to characterize the PGE2 mediated signaling mechanisms that counter diaphragm atrophy, and to assess age-associated differences in outcomes.Expected Results and Impact: This proposal aims to characterize a novel therapeutic strategy that will strengthen the diaphragm muscles and therefore reduce the duration of mechanical ventilation. This research has the potential to have a major clinical impact and benefit elderly patients most affected by prolonged ventilation due to pneumonia or COVID-19, aiding in weaning patients from respiratory support and substantially decreasing their mortality rates.",,2021,Baxter Laboratory for Stem Cell Biology Stanford University,95126.73,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,United States of America,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Pre-clinical studies",2021 +P28461,200920,Persistent Liquidity Traps and Macroeconomic Policies in Open Economies,"The recent years of very low or even negative interest rates represent a challenge for economic policy and economic analysis. What was expected to be a temporary period of very low interest rates has become persistent. The recent COVID shock is exacerbating this situation. Situations of liquidity traps can be analyzed in Keynesian or New Keynesian frameworks, where demand is insufficient. Macroeconomic policies in this environment are relatively well understood. However, when liquidity traps become persistent there are dimensions other than demand that become important. The objective of this project is to analyze persistent liquidity traps and the impact of macroeconomic policies in an international context. The project will emphasize the role of liquid assets in environments where some agents need liquid assets because of financial constraints. The models are non-Ricardian with agent heterogeneity. We will follow the particularly simple and tractable framework proposed by Woodford (1990}.The project is made of two subprojects that examine two different environments. The first subproject studies a two-country model where one or the two countries are in a liquidity trap. More precisely countries may hit the Effective Lower Bound (ELB) on nominal interest rates. An interesting case is the one where a creditor country is at the ELB, but not the debtor country. This could represent the Eurozone and the US in recent years. In the current situation, after the COVID shock, the two countries would be at the ELB. Several questions will be analyzed. First, what type of shocks can push countries into a persistent liquidity trap and can there be a transmission of liquidity traps across countries? Second, what is the impact of shocks and what are the channels of transmission? Third, what are the desired macroeconomic policies in each country? Part of the work could be done analytically, especially in the steady state. But the most important part has to be done through numerical simulations. This will allow us to understand the dynamics combining the more standard demand-side effects in the short run with the more persistent effects in the medium run. Also it would be interesting to use the model to understand the impact a temporary COVID shock in a low or negative interest rate environment and the appropriate policy response.The second subproject will develop a model of a small open economy receiving large capital inflows. This model is inspired by the Swiss economy, which is considered as a safe haven. A sustained period of large capital inflows can push this economy into a persistent liquidity trap. This raises important issues for monetary and fiscal policy, but it also raises theoretical questions related to the equilibrium properties and the determination of inflation. When the economy hits the ELB, the Taylor principle for monetary policy is not longer satisfied so there may be no stable solution for prices and the nominal exchange rate. On the other hand, fiscal policy may play a more important role and may allow to determine a stable equilibrium. This would change the behavior of inflation. This effect is more likely to occur in a safe haven economy where the demand for bonds is less elastic in times of turmoil. The current increase in government debt can also be taken into account. Once these issues are well understood, we can examine the impact of macroeconomic policies. As in the first subproject, the first part will be analytical and the second part will be numerical.",,2024,Département d'économie Université de Lausanne Internef,231815.22,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P28472,215567,Arms race between viral evolution and population immunity - Understanding the impact of antibody pressure on SARS-CoV-2 variants and human endemic coronaviruses.,"BackgroundImmense scientific progress has been made during the Covid-19 pandemic, but the future of SARS-CoV-2 remains unpredictable. With the emergence of the Omicron variant of concern (VOC) a new phase of the pandemic was entered. Although genomic surveillance could identify the strongly mutated Omicron quickly, only biological experiments could demonstrate an altered viral phenotype compared to earlier VOCs: A novel SARS-CoV-2 serotype of unknown origin with strong immune-escape from antibodies derived by earlier infection, vaccination and even hybrid immunity. Since then, high infection activity from Omicron BA.1, BA.2 and BA.5 were observed, with negative impacts on health and economy. Within a short time, a very high viral diversity within the Omicron clade developed but with heterogeneous geographical patterns. This suggests that viral evolution towards new variants is currently mainly driven by underling immunity, that is now a heterogeneous background of immunity to earlier variants, vaccination, and breakthrough (re-) infections. An increase in SARS-CoV-2 population immunity may even impact endemic coronaviruses by the same mechanism of immune pressure.Project & AimsIn the proposed project, I will build on work of the last 2.5 years on phenotypic characterization of SARS-CoV-2 and in vivo risk assessment of variants, including earlier experience of complex culture models and research on coronaviruses other than SARS-CoV-2.In this proposal I will focus on 1.) Emergence of immune escape properties in vivo in contemporary SARS-CoV-2 isolates through evolutionary pressure mediated by antibodies derived from prior infection with various VOCs, vaccination and hybrid immunity. We will sequentially passage virus isolates on primary human airway cultures in presence of anti-SARS-CoV-2 antibodies derived from characterized convalescent, post-vaccine and hybrid-immune sera. Isolates of all passages will be fully sequenced to see development of mutations. They will be phenotypically assessed for neutralization by sera representing the complexity of current population immunity (unvaccinated Omicron-exposure, vaccination, multi-exposure after vaccination and reinfection). In addition, we will assess replicative capacity in human primary airway cultures. We will compare them to naturally arising immune escape variants or selected recombinant viruses 2). Intra-host evolution of SARS-CoV-2 in chronically infected patients including their phenotypic characterization as one scenario of evolution of immune escape variants 3.) Intra- and post-pandemic evolution of endemic human coronaviruses (HCoVs) through immune pressure from SARS-CoV-2 immunity and/or disruption in transmission during the pandemic. Pre-, intra and post-pandemic HCoVs will be sequenced and isolated to assess for immune escape by neutralization assays.Impact & RationaleThe transition phase from a pandemic to an endemic state is characterized by the arms race between increasing population immunity and viral evolution. Developing in vitro models to understand the evolution of immune escape is a forward-oriented approach, rather than just assessing new variants when they emerge. The coming years offer a once-in-a lifetime opportunity for a virologist to observe the establishment of a new human virus into the human population, including a possible impact on related viruses. Due to ongoing collection of virus isolates and serum panels, access to patient cohorts and continuous genomic surveillance for SARS-CoV-2 and HCoVs, our Centre is in an ideal position to study this.",,2027,Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève,836875.46,Human Populations | Viruses,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Immunity | Disease transmission dynamics",2023 +P28473,196383,Phenotypic characterization of a SARS-CoV-2 clinical strain bio-bank and risk assessment of evolving virus variants,"BackgroundIn late 2019 a novel coronavirus (CoV), now termed SARS-CoV-2 and the causative agent of the disease COVID-19, emerged in China. SARS-CoV-2 has caused a pandemic and an unprecedented international health crisis of unknown outcome. Although coronaviruses are known to frequently cross species barriers with SARS-CoV-2 as the 7th human pathogenic coronavirus, we still lack profound knowledge on the genomic alteration for host adaptation. As this virus entered into the human population recently with an estimated spill-over event from an yet unknown animal host in late 2019, it is expected that SARS-CoV-2 will undergo genetic mutations and further adaptation to the human host during the course of the pandemic. Of note, adaptations can go either way and enhance but also mitigate, e.g. virulence or disease severity. In this outbreak, metagenomic data are readily available to track the epidemic in real-time, but in silico analysis based on sequence data alone cannot sufficiently predict viral phenotypes. Potential changes in the replicative capacity, in receptor affinity, interferon susceptibility or escape from adaptive immune response of evolving strain will have significant impact on public health, treatment or vaccine strategies. However such changes can only be assessed by functional experimental studies using relevant clinical virus strains. Still, isolation of new viruses is often limited to a few initial strains at the beginning of an epidemic but abandoned in the long run, leading to a lack of low-passage virus isolates representative of the diversity of relevant circulating and evolving strains.Project & aims.In the proposed project, we aim to set up a SARS-CoV-2 strain biobank of virus isolates from well-defined clinical samples over the course of the epidemic and assess key phenotypic traits of low-passage strains. In the project, we will 1.) isolate at least 30 clinical strains during the first 2 years of the epidemic from patients at the University Hospital of Geneva and across Switzerland 2.) characterize them for replicative capacity on cell lines and primary airway cultures as well as interferon susceptibility 3.) analyse neutralizing capacity of early-epidemic convalescent sera against evolving SARS-CoV-2 variants and VSV-based-pseudotyped viruses harbouring SARS-CoV-2 spike-protein variants as surrogates for work under BSL-2 conditions. Metagenomic and related clinical data are available through a prospective clinical cohort study on COVID-19. Our functional data on key traits of evolving virus variants in addition to viral metagenomic data can help to guide and adapt immediate response strategies to this pandemic.Impact & rationale Our functional data on key traits of evolving virus variants complement viral metagenomic data and can help to guide and adapt immediate response strategies to this pandemic. Results will be aligned in real-time to collaborating groups from epidemiology, immunology and clinical research to adapt their analysis in the light of evolving variants. All SARS-CoV-2 isolates and surrogate viruses will be made available to the research community. Due to the unique position of our Centre with access to clinically well-defined specimens and an adjacent virology laboratory with BSL-3 facilities, our proposal is central and highly synergistic to the emerging research landscape on SARS-CoV-2 currently forming in Switzerland. With the proposed project, we will be able to centralize and maximize the collaborative output of our Centre necessary to rapidly address this complex and challenging situation.",,2022,Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève,307998.19,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Supportive care, processes of care and management",2020 +P28474,196270,"Coronavirus epidemic in Switzerland: integrating clinical, epidemiological, biological and behaviour with mathematical modelling","Background: In late December 2019, a novel coronavirus named SARS-CoV-2 was identified, with first cases occurring in Wuhan City, Hubei Province, China. A massive spread of the disease (COVID-19) in China was soon followed by increasing numbers of cases in many other countries. In Switzerland, the first case was detected on February 25th. Since then the number of cases has increased rapidly to 3028 as of March 18. To better understand the transmission of the virus in Switzerland, and to integrate effective interventions, it is necessary to integrate international research findings from published literature and pre-print articles, with national surveillance data, and information from the internet and social media.Objectives: The overall aim of this project is to analyze and integrate these different data sources as quickly as possible, thereby creating a novel interdisciplinary surveillance system for SARS-CoV-2/COVID-19 in Switzerland. The system will be flexible so that it can be adapted to future outbreaks.Methods: We will perform several independent sub-projects that also inform each other. Some of the findings will be integrated into a mathematical simulation model of COVID-19 transmission in Switzerland. The first sub-project is a semi-automated systematic review of the scientific literature (including preprint articles) on SARS-CoV-2/COVID-19. We will perform repeated topic modelling (using e.g. Latent Dirichlet Allocation or UMAP algorithms) of all available articles. Each article will be attributed to one of several topics and the process is repeated several times. The aim is to quickly identify articles of various topics of interest (e.g. clinical course of disease, mathematical models of spread of disease, economic consequences, biologic studies on vaccine development and immunologic response, etc), without the need to define exact search terms a-priory. Papers will be made accessible and searchable through a web user interface, as well as an API. The findings will be made publically available, and will inform both the Swiss and the international response to the epidemic. Key parameters for the parameterization of the mathematical model, will be extracted automatically or by hand search from the identified full text articles. As a possible extension we will also analyse social media data (e.g. from Twitter, Facebook and Reddit) in real-time which may help to understand how behaviour of individuals changes as the epidemic evolves. The second subproject concerns the analysis and comparison of existing Swiss surveillance data. Data include i) a sentinel surveillance system of 10 Swiss hospitals (project being finalized; partly funded by the Federal Office of Public Health FOPH; O Keiser is the principle investigator (PI)); ii) Sentinella (Influenza/COVID surveillance by general practitioners; available by FOPH); Grippenet (app to report influenza-like symptoms voluntarily; PI A Flahault). In addition we aim to integrate whole genome sequence data as soon as they become available from the national reference lab for emerging viruses in Geneva (PI I Eckerle). We will compare the findings from the different data sources to each other and to published literature. For example, we will analyse predictors for progression and outcome of the disease. We will use state-of-the art analyses methods including e.g. regression analyses. As third sub-project we will develop a novel mathematical model for Switzerland that includes the progression and transmission of the disease. and that will be directly linked to the surveillance data. The model will be parameterized in real-time using the literature and surveillance data where possible; it will build on our previous expertise with mathematical modelling and include how individuals react to the epidemic.Relevance of study: Combining the mathematical model with the other sub-projects will give us a deeper understanding of the COVID-19 epidemic, and allow us to evaluate the effectiveness of interventions (e.g. by identifying risk factors, by improving the management of hospital beds; by focusing interventions on areas of intense viral circulation, and by detecting more or less virulent strains). Our interdisciplinary research project combines analyses of traditional surveillance data, fundamental research, phylogenetic analyses and mathematical modelling. We bring together epidemiologists/statisticians, modellers, clinicians with expertise in infection control and prevention and virologists with longstanding expertise on Coronaviruses. Our project will provide insight about the course of the disease and the circulation of COVID-19 in Switzerland. Possible interventions will be discussed with the Federal Office of Public Health. All relevant scientific findings from the project will be made available immediately on a dedicated website.",,2023,Institut de Santé Globale Institute des Etudes Globales Université de Genève,361429.66,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +P28476,200295,"Apelin-ACE2 axis fate in hypertension and macrophage syndrome as complications in COVID-19: focus on gender, age and comorbidities.","Age and cardio-metabolic risk factors are one of the main determinants of SARS-CoV2-induced disease severity and death. 30 to 40% of the patients present severe acute cardiovascular damages. Consequently, heart failure is a prominent cause of death in COVID-19 severely ill patients. Besides, it is also expected that patients recovering from COVID-19 may develop chronic cardiovascular diseases (CVD). Interestingly, the angiotensin-converting enzyme 2 (ACE2), a transmembrane protein, is the main target of the SARS-CoV2 to infect the host cells and represents a critical connection between immunity, inflammation, and cardiovascular disease. A puzzling and unsolved question relies on the effect of medications taken by a large number of CVD patients that interfere with the renin-angiotensin system (RAS). One of the crucial observations for ACE2 is that its levels can be increased by the use of anti-hypertensive drugs that consequently might increase the level of virus infection for treated patients. This issue is yet to be evaluated. Whether patients with COVID-19 and hypertension treatment present a higher risk and should modify their anti-hypertensive medications is unproven, and experimental evidence is required. Understanding the acute and chronic cardiac damages caused by the hijacking of ACE2 (as occurring with by SARS CoV-2) with or without anti-hypertensive treatment is of paramount to define therapeutic strategies for COVID-19 patients, to reduce the mortality.Therefore, in the first part, our objectives are to 1) quantify the tissue RAS agents such as ACE2 and receptors in related to age, sex and health status in rodent models with several physiological and pathophysiological heart alterations, and 2) investigate different therapeutic strategies in these models based on the modulation of ACE2 focusing in particular, on the Apelin-ACE2 axis. Activation of Apelin and its receptor Aplnr axis increase the expression of ACE2 and interfere with the RAS by decreasing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, and angiotensin receptor 1 (AT1R).In addition, using global transcriptomic and system biology approach, we have identified APELIN-ACE2 axis as one of the important pathway altered during cardiac aging. Apelin-Aplnr axis regulates several transcription factors like SMAD2/3/4, PGC-1a, KLF2, and MEF2, and signalling pathways like PI3K/Akt, ERK1/2 and AMPK. Interestingly, 55 amino acid proapelin is cleaved to its active form of 13 amino acids by PCSK3/Furin, which is an essential protein involved in the processing of SARS-CoV2 spike protein. These findings suggest a possible role of Apelin-APLNR axis in SARS-CoV2 cellular entry. Therefore, in the second part, we aim at exploring whether 1) activation and 2) inhibition of apelin signalling pathway would regulate cellular proteins involved in SARS-CoV2 viral entry in rodents. In mild and severe Covid-19 patients, apelin levels will be correlated with various cardiac, kidney and lung function parameters.Severe Covid-19 patients exhibit features of systemic hyper-inflammation termed as macrophage activation syndrome or cytokine syndrome. Apelin signalling pathway plays a crucial role in macrophage physiological and pathological functions. However, its role in macrophage activation syndrome is not well studied. In addition, elevated ROS production has been critical for the phagocyte action and killing of the invading pathogen, making it an integral part of the innate immune response. Additionally, apelin signalling pathway also regulates ROS production. Based on our preliminary results, we have seen that infusion of AngII to p47 phox (an enzyme involved in ROS production) knockout mice results in macrophage activation syndrome, characterised by increased expression of several cytokines. Here, in the third part, we aim to 1) decipher the role of apelin signalling in macrophage activation syndrome and 2) assess the role of p47phox in macrophage activation syndrome-like condition and its effect on Apelin-Aplnr, ACE-2 axis.Overall the project will simultaneously address the disease mechanism and optimisation of therapy for COVID-19 patients. In particular, we expect to define the effect of anti-hypertensive treatment on ACE2 modulation related to conditions such as age, gender and macrophage activation syndrome. This will provide the necessary information concerning the beneficial or deleterious effect on this multi-drug therapy. The collaboration will expose both the institutes to their state-of-the-art facilities, leading to overall growth and advancement of the area. Knowledge gained from this proposed study will be very critical for future COVID-19 patient care and bears a very high clinical importance. The project paves the way to the next step on human interventional studies implementing the evidence-based results.",,2025,"Department of Clinical Research, DKF Division of Cardiovascular Surgery University Hospital Bern, Insel",378349.47,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Clinical characterisation and management | Therapeutics research, development and implementation",Prognostic factors for disease severity | Disease pathogenesis | Pre-clinical studies,2021 +P28484,205796,Trade Packages: Making Trade Agreements Work in the Service of Society,"International trade agreements typically benefit the national welfare of the nations that sign them. However, they also generate economic displacements as well as negative social and environmental spill-overs. The traditional approach to address these negative spill-overs has been to rely on domestic flanking policies, which are de-linked from the trade agreement itself. This approach, however, has not always worked well. Too often trade has been liberalized internationally, but domestic lawmakers have failed to enact the needed measures to address economic disruptions and spill-over effects on the environment and society. This has sapped the support for trade. Popular resentment of 'globalisation' has driven anti-trade sentiments to heights not seen since the 1930s in key geographies. A trend that has been intensified further with the COVID-19 Pandemic. This is having serious consequences for the multilateral trading system. Although some rebalancing may be needed, the risk is that moves towards de-globalisation compromise the massive benefits that open trade have brought to countries. This project will explore if and how trade agreements could become a vehicle to address these spill-overs more directly by including the necessary flanking policies that offset the negative effects either (i) in the trade agreement itself or (ii) anchored in the domestic legislation implementing the trade agreement (hereafter ""package treaties""). The project is inspired by early examples of such inclusions in recent trade agreements. There is a need for an innovative and interdisciplinary effort (international economics, law, and relations) to further explore such tools for trade and identify if and how these modalities can be politically realistic and socially effective for ""packaging"" trade agreements, be it in the agreement itself or its domestic implementation, with complementary policies in ways that pre-empt, minimise or redress the disruptions. The findings have the potential of reshaping the way future international trade agreements are developed and how domestic trade policy can be anchored to required flanking policies.This project will fill important gaps in the literature, by expanding on emerging scholarship on package treaties by: (i) Offering a deeper understanding of the spill-over effects that trade agreements have on jobs, income distribution, the environment, and gender. We will develop recommendations on how to integrate ex-ante impact assessment tools into the scoping and negotiating process to better account for spill-over effects on job, income distribution, the environment, and gender. (ii) Mapping out the different ways countries have addressed (or not) spill-over effects when they adopted international trade treaties. We will produce a database of flanking provisions that have been ""packaged"" in trade agreements or domestic implementing legislation to address the spill-overs, illuminate the domestic political dynamics behind those choices, and seek to understand the reasons why in other cases negative spill-over effects are not adequately addressed at the domestic level. (iii) Exploring the effectiveness and practicality of trade packages as a tool to address the spill-over effects. We will develop in-depth case studies of the various models of existing ""package"" trade agreements, explore their pros and cons, trace their ensuing effects, and assess their consequences. We will also explore why package treaties have not been used in other specific cases. (iv) Developing recommendations on if and how package treaties could be further used, considering economic and political optimal fits with different individual national solutions, and highlighting their advantages and challenges. The results will be published into at least: two special issues/edited interdisciplinary book volumes on package treaties, four co-authored peer reviewed articles, three related doctoral theses, a stand-alone database of flanking policies, working papers and policy briefs, two large conferences on ""package treaties"", etc.The three co-applicants: Richard Baldwin (Professor of International Economics), Joost Pauwelyn (Professor of International Law) and Cedric Dupont (Professor of International Relations) bring extensive, complementary experience and past experience working together. They will work with a team of three Post-Doc researchers and three Phd students.",,2026,"Centre for Finance and Development Science politique IHEID, Graduate Institute",2017207.11,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2022 +P28489,220329,Zoonotic risk assessment of Swine Influenza A viruses,"Background: Swine influenza is a highly contagious respiratory disease in pigs that can cause significant disease burden and substantial production and economic losses in the swine industry. The disease, caused by swine influenza A viruses (swIAV), is currently enzootic worldwide and affects millions of pigs yearly. Cross-species transmission has been well-documented for influenza A viruses, and swIAV is no exception, with the potential to cause severe consequences to both animal and human health. Pigs play an important role as ""mixing vessels"" for the generation of novel human pandemic influenza A viruses, meaning they can be infected by influenza A viruses from a variety of avian and mammalian species. As such, pigs play a crucial role in diversifying influenza A viruses and emerging new swIAV variants, some of which have zoonotic potential. However, despite the occurrence of multiple devastating influenza epidemics and pandemics in the past, our knowledge of the zoonotic potential of swIAV that circulate in pig populations in Europe is limited.Objectives and aims: Despite the recent increasing genomic surveillance efforts for swIAV across Europe, our current understanding of the viral determinants and biological characteristics influencing the zoonotic potential of swIAV is limited. In this project, we will leverage the genomic surveillance and phylogenetic analysis data of swIAV generated during the ESFLU COST Action to identify swIAV variants of interest (VOI) and (I) create a reverse genetic clone repository for swIAV that enables (II) comprehensive biological characterization and risk assessment of swIAV in biologically relevant in vitro models of the human and swine respiratory epithelium. Together, these data will increase our understanding of the viral determinants and biological characteristics influencing viral fitness, virus-host interactions, antiviral resistance, and the zoonotic potential of swIAV circulating in European pig populations. Expected results and impact: The proposed project will increase our understanding of the zoonotic potential of swIAV circulating in European pig populations and provide crucial phenotypic data in biologically relevant human and swine respiratory epithelium models. This biological data will complement the surveillance data collected by different members of the ESFLU COST Action and can be incorporated into an overall risk assessment of the zoonotic potential of various swIAV. Furthermore, it may provide insight into the progression or pathogenesis of swine influenza in pigs. Altogether, the proposed project will complement and enhance the existing ESFLU COST Action, strengthening the overall preparedness in Europe, including Switzerland, to rapidly identify and characterize circulating swIAV variants with zoonotic and pandemic potential. Combining the knowledge generated during the proposed project with the ESFLU COST Action will advance the scientific understanding of how certain swIAV variants can successfully establish themselves among different species, contribute to the European network on swIAV, and increase global pandemic preparedness.",,2027,Institut für Infektionskrankheiten Universität Bern,422059.76,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2024 +P28490,207675,Deciphering the interferon system in bats,"Background:Bats are the second most speciose group of mammals after rodents, with more than 1400 species that comprise over 20% of all known mammalian species. While several important aspects of bat physiology and behaviour have been studied intensively over the last decades, the importance of bats as a reservoir host for emerging and re-emerging viruses has become increasingly apparent after several recent viral outbreaks. Many of these viruses pose a serious risk to both human and animal health, as illustrated by recent outbreaks of Hendra virus, Nipah virus, Ebola and Marburg viruses, SARS coronavirus (SARS-CoV), and most recently by SARS-CoV-2, the causative agent of COVID-19. One key unresolved question in the field is why there are so few documented cases of virus-related disease in bats given the high prevalence of viruses hosted by these mammals, which raises the pertinent question; what makes bats an ""ideal"" reservoir host for so many emerging viruses.Working hypothesis and aims:Despite the importance of bats as a reservoir host for many emerging and re-emerging viruses, our current understanding of virus - host interactions in bats, and in particular our knowledge of the interferon (IFN) system in bats, remains rudimentary. While much progress has been made in recent years, most of the underlying viral and host determinants affecting the successful establishment and immune control of viral infections in bats remain elusive. Herein, a major hurdle is the lack of an appropriate unified biologically relevant model system and molecular tools to study virus - host interactions in bats that can be directly compared to analogous models of other mammals. As a first step toward deciphering the IFN system in bats we will (I) establish a primary cell culture repository of bat airway epithelial cells and (II) a bat-specific molecular tool box to determine (III) the biological role of type I and III IFNs in bats and (III) cellular distribution of key components of the bat IFN system. Finally, we will (IV) functionally characterize the bat IFN response during virus replication to gain a deeper insight of the bat innate immune response during viral infection.Expected Significance:The proposed studies will generate novel and detailed knowledge on the biological role of type I and III IFNs in bats and will specifically determine how the bat IFN response is temporally regulated within the heterologous respiratory epithelium in the context of viral infection and whether this is different from other mammals, such as humans. This knowledge is of high impact given the importance of bats as potential reservoir hosts for so many emerging viruses and will be indispensable to better understand what makes bats 'special' as reservoir hosts for so many emerging viruses.",,2026,Institut für Infektionskrankheiten Universität Bern,880729.06,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2023 +P28493,209986,Short- and long-term impacts of Covid-19 on VET: Strengthening VET in times of crises,"The Covid-19 pandemic has affected the whole educational system profoundly. The ensuing challenges have been particularly pronounced for vocational education and training (VET). In many training occupations, learners were not only faced with online teaching in vocational school but also with the temporary closure of firms or the prolonged absence of vocational trainers due to home office regulations or work overload. Although VET was hit particularly hard, the bulk of studies on the effect of the pandemic for pupils, students and teachers has focused on classroom teaching. The consequences of the pandemic for training in firms and for the demand and supply of apprenticeship positions has, to the best of our knowledge, not been addressed systematically. However, if we take into account that VET is the most prevalent type of upper-secondary education in Switzerland, the impact of the pandemic is potentially extensive and affects a large part of all young people. It hampered not only their occupational choice process and their possibilities to gain insights into apprenticeships and to search for vacant apprenticeship positions, but also their learning processes in the firm and in vocational schools. Moreover, the economic downswing caused by the pandemic led to a temporary increase of youth unemployment and had thus a detrimental effect on VET graduates' labour market integration. Training companies faced the challenge of recruiting as well as sustaining practical training under difficult and unpredictable conditions (distance learning, company closures, short-time work, home office, etc.). However, the gained experiences have also shown that the different industries and occupational fields as well as the different regions (rural/urban; French-, Italian-, German-speaking) were affected unevenly by the pandemic. Against the described background, the proposed project aims at investigating the impact of the Covid-19 pandemic on dual vocational education and training in Switzerland. We will focus on differences between occupational fields and regions regarding the training process, the demand and supply of apprenticeship positions and young people's educational trajectories and labour market entry. Regarding the training process, we will investigate the measures taken by training firms and professional organizations from the world of work (OdA) to ensure that apprentices acquired vocational skills and knowledge and were able to complete their training successfully (Work Package 1). Furthermore, we will analyse whether the pandemic led to an adaptation of recruitment strategies, training regulations and practices. Regarding the demand and supply of apprenticeship positions, we will investigate whether the pandemic had an impact on young people's search preferences and chosen training programmes one the one hand and firm's supply for apprenticeship positions on the other hand (Work Package 2). Regarding educational trajectories and labour market entry, we will ask whether the pandemic led to more turbulences for some groups of learners, such as delayed transitions to certifying upper secondary training, premature contract terminations, repetitions, final exam failures, unemployment, or lower wages at labour market entry (Work Package 3). The proposed project is based on a mixed-methods approach and will combine several data sources. These include a document analysis, semi-structured qualitative interviews with representatives of professional organisations, firms and apprentices, a quantitative online survey of firms engaged in vocational training, the analysis of changes in the apprenticeship market using data of Swiss online apprenticeship platforms, as well as the analysis of educational trajectories and labour market entry based on LABB data linked with additional administrative and survey data. The expected results aim at increasing the resilience of the VET system to withstand future crises by systematically evaluating the experiences and employed measures of firms and the effects of the pandemic on the demand for training and on training outcomes. To reach this aim, the project will provide a systematic overview of the challenges faced during (and after) the pandemic in different occupational fields and regions. Furthermore, the project will provide evidence regarding the advantages, disadvantages, and preconditions of applied measures. This will facilitate the development of future recruitment and teaching strategies. Occupation-specific workshops and a symposium with representatives of training firms and organisations of work are planned in order to comprehensively assess past, present and future experiences, changes in teaching and training practices, as well as information, counselling and recruiting strategies. An advisory board with stakeholders from the government and from organisations of the world of work (OdA) will accompany the project including the implementation of the results into VET practice.",,2026,Abteilung Bildungssoziologie Institut für Erziehungswissenschaft Universität Bern,616949.26,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28499,198388,AI-multi-omics-based Prognostic Stratification of COVID-19 Patients in Acute and Chronic State,"COVID-19 is a pandemic disease with tremendous consequences spreading at fast pace. Key measures to control and manage this currently untreatable disease, and to provide adequate patient care are rapid and reliable diagnosis as well as severity assessment. While most patients develop only mild symptoms or are asymptomatic altogether, others exhibit severe courses that are associated with a high mortality rate. Of the initially moderate to severe cases, some recover completely while others deteriorate with the need of being put on invasive ventilation support or even extracorporeal membrane oxygenation. The long term effects on the lung in severe cases are largely unknown to date. First publications suggest that pulmonary fibrosis could develop. In addition, over the last weeks we have learned that the prognosis depends not only on pathological changes in lung tissue but also on changes in a variety of other pathological sites that the virus attacks such as the vessel wall. The findings on chest imaging for COVID-19 are often typical, but ultimately not specific and overlap with other infections, including influenza, H1N1. Despite early positive reports, the role of radiology in the management of COVID-19 remains to be defined. In this project we aim to develop and test an AI-based multi-omics system that combines and uses information from chest CT, laboratory parameters, and clinical data to a) assess the current state of a patient in the acute phase and to forecast seven-day progression and b) to predict chronicity (chronic lung damage). More specifically, our research is aimed at investigating whether an ensemble of multi-omic, patient-specific information can be used to predict patient outcome and ultimately optimize patient care. In addition, we intend to interpret and understand the importance of each item in the ensemble in terms of learning and disease outcome prediction. Special emphasis will be placed on the vascular situation and certain lung changes (bronchiectasis). Furthermore, through the predictive capabilities of the proposed AI-based multi-omics approach, we aim to better understand how COVID-19 progresses over time, since it is largely unknown why patients differ in disease progression. Finally, once the AI system is established, we intend to monitor treatment response in patients receiving different treatments (e.g. Remdesivir, Actrema). To date, we have access to more than 2'000 chest CTs of patients with laboratory-proven COVID-19 infection as well as their lab parameters, age, gender, and patient history. The majority of COVID-19 positive cases will be provided from centers in Northern Italy. As controls, we will include 1'200 cases with similar symptoms who have had pathological CT findings (pneumonias of various causes) before 12/2019 to rule out that these symptoms could have been caused by COVID-19 and 1'000 negative controls with normal chest CT. We will measure the performance of the AI-based computational engine, as well as the contribution of each individual variable to the classification and prediction performance of the proposed system. Quantitative metrics used to analyze the results include sensitivity, specificity, accuracy, positive predictive value and area under the curve (AUC) of the Receiver Operating Characteristic (ROC).Determining faster and more accurate prognostic stratification for COVID-19 patients based on the proposed AI-system is expected to contribute to better and more appropriate patient care and improve the efficiency of physicians. Better understanding of the different parameters and their interaction for the outcome of COVID-19 patients can shed new insights regarding the disease progression patterns of COVID-19, which could be of crucial importance for the treatment of critical patients.",,2023,"Insel Gruppe Bern Universitätsinstitut für Diagnostische, Interventionelle und Pädiatrische Radiologie",680973.94,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Impact/ effectiveness of control measures | Prognostic factors for disease severity,2020 +P28504,221584,Ancile: novel antibacterial and antiviral coating,"Each year, antibiotic-resistant bacteria kill over 1 million people; by 2050, this toll is expected by the World Health Organization to reach a shocking 10 million annual deaths. Apart from the enormous social and humane impact, the damage to the economy will far exceed that caused by the Covid-19 pandemic. Various surfaces in public spaces are dangerous reservoirs for bacterial and viral infections. For example, the Covid-19 viral particles survive on plastic surfaces or even stainless steel for up to three days, while E. coli and S. aureus bacteria dwell on such surfaces for up to several months. All these pathogens can be killed by simple alcohol disinfection; however, alcohol can stay on a surface for only a few seconds; therefore, it should be applied thoroughly. At the same time, according to the Swissmedic report, cleaning and disinfection processes are not followed in 53% of Swiss hospitals. What if we could turn every public place surface pathogens use as a means of transmission among people into a weapon against microbes and viruses? Three potential ways to achieve this goal can be envisioned.The first is to change the texture of the public surfaces. Special coatings with micro- or nanoscale protrusions are known to kill bacteria and inactivate viruses. An example can be found in nature: nano-textured surfaces of cicada wings are bactericidal, and millions of years of evolution have not been sufficient for the microbes to develop resistance to this mechanism6. Why not use this principle in human public health?The second approach is to deposit nanoparticles of some metals, such as silver or copper. Again, bacteria and viruses show no signs of developing resistance to such protection. And the third approach is to use antimicrobial peptides. Can these mechanisms be used on public surfaces?Moreover, why not combine the nano-texturing mechanism with metallization and/or antimicrobial peptide applications to ensure maximal and universal antibacterial and antiviral efficiency, secured from the possibility of resistance development?This is the essence of our project. Stemming from our discovery of the bioinspired self-assembly mechanism of nano-textured coatings, we have further learned how to load anti-infective metal ions into the textures. The formulations we develop aim at single-step spraying or brushing with the patented mixture of proteins and fatty acids. Low-cost production should permit efficient covering of various surfaces with durable, non-irritant, yet strongly bactericidal and antiviral functionalities. Such public surfaces as medical facilities and laboratories, public vehicles, hotels and shops, food-packaging areas and restaurants, air ducts and air ventilation systems, schools and childcare facilities, surfaces in animal farms, etc. - can all be treated with our sprays to turn what used to be reservoirs for pathogen propagation into a weapon against these pathogens. A significant change in the public health paradigms may emerge from this work.",,2024,Demaurex Lab Department of Cell Physiology and Metabolism University of Geneva,158934.7,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2023 +P28505,191762,"The molecular basis of adaption of aedes mosquitoes, vectors of viral diseases, to saltwater environments","Vector-borne diseases constitute an enormous health burden, particularly in tropical and sub-tropical regions. Mosquitoes of the genus Aedes transmit the viruses responsible for yellow fever, Dengue, Zika and Chikungunya. Dengue is rapidly reaching pandemic proportions and currently constitutes a major health problem in Sri Lanka. At the same time, cases of Chikungunya are increasing. In the absence of vaccines or drugs for these diseases, vector control is the only means of limiting their spread. Like many other mosquitoes, Aedes species breed in stagnant fresh water. A surprising recent finding is that Aedes mosquitoes in Sri Lanka have adapted to breed in brackish water as well, thereby extending the area where transmission of Dengue virus can occur. The aim of this collaborative grant is to elucidate the physiological and molecular basis of adaptation using next generation sequencing (RNA-seq) and immuno-electron microscopy. The project also contains two training components - a workshop to teach bioinformatics to students in Sri Lanka and two three-month stays in Swiss laboratories for Sri Lankan PhD students to learn recombinant protein technology and electron microscopy. Wells with brackish water are common in households on the Jaffna Peninsula in northern Sri Lanka and may have contributed to selection of Aedes mosquitoes that are tolerant to salinity. At present, national and international dengue control guidelines target only fresh water breeding sites. This knowledge gain is expected to help control dengue transmission. Furthermore, understanding the basis of adaptation has wider implications for the spread of other mosquito-borne diseases, including malaria and West Nile virus, which are transmitted by other species of mosquitoes.",,2024,Institut für Parasitologie Universität Bern,164171.95,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Vector biology",2020 +P28510,198255,"Devils dance: complement, NETs and thrombosis in COVID-19","Corona virus disease 2019 (COVID-19) presents with flu-like symptoms and viral pneumonia, which may progress to acute respiratory distress syndrome (ARDS) and occasionally to multiple organ dysfunction syndrome (MODS). Cardiovascular complications in the form of arterial and venous thrombosis contribute to ARDS, MODS and fatality. So far, there is no effective therapy for COVID-19. There is evidence that an overwhelming host response of the innate immunity contributes to the development of ARDS and vascular complications. Preliminary data suggest a role of complement and neutrophil activation in the form of neutrophil extracellular traps (NETs) in this response. The aim of the proposal is to identify complement activation (including the specific pathways involved) with subsequent neutrophil activation in the form of NETs to be the main drivers for the development of ARDS and microvascular complications in COVID-19. The results will form the base to establish and implement timely therapies targeting complement- and neutrophil activation in order to prevent and/or treat ARDS and microvascular complications in COVID-19 patients. The methodology applied in this project relies on the applicant's expertise in complement and neutrophil biology to measure and subsequently dissect complement- and neutrophil activation pathways in COVID-19. The obtained biochemical results will be related to clinical data of COVID-19 patients included in this study. The planned analysis will also include testing for genetic susceptibility potentially predisposing for an overwhelming host response to SARS-CoV-2, as evidenced by an excessive complement activation and NET formation. Finally, we will identify the contribution of complement and NETs in hypercoagulability using assays to follow coagulation in real-time. All the assays and techniques described in the current proposal are operational. We expect to establish surrogate markers in this innate host immune response in order to identify either patients at risk for complications (e.g. ARDS, microvascular complications) and/or patients suitable for a therapy targeting complement and/or neutrophils. The current application is embedded in a strong national and international complementary scientific network enabling a) access to blood samples and clinical data from COVID-19 patients treated at different University Hospitals in Switzerland; b) access to national and international specialized infrastructures and laboratory techniques, e.g. genetic platforms (collaboration with the University Hospital Geneva) and assays for complement activation (Sanquin Research, Amsterdam, the Netherlands); and c) participation in intervention studies targeting complement (University Hospital Basel). This strong scientific network is a prerequisite to accomplish the proposed project successfully in time. The results of the current proposal will provide the molecular mechanisms of complement activation with subsequent neutrophil activation and establish their significant role in the pathogenesis of hypercoagulability in COVID-19. The current study will identify the level and the pathway on which complement - and neutrophil inhibition will be most effective and hence will form the base to introduce therapies targeting either complement- or/and neutrophil activation. Especially in the complement field, there is a plethora of new inhibitors emerging targeting different complement pathways at different levels, but only a few are tested in clinical studies or are available for other indications than COVID-19. The results of current application will contribute to accelerate clinical testing and implementation of candidate drugs targeting complement providing a rational and effective therapeutic strategy to treat COVID-19.",,2023,Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor Inselspital,622429.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +P28511,212295,Poverty in Later Life in Rural Switzerland and the U.S.: A Comparative Case Study,"While poverty is an economic and social status, it is also an experience. This research project, that will take place in two rural and mountainous regions of Switzerland and the U.S., seeks to understand the experience of poorer older people in such contexts. Existing literature shows that there are significant levels of poverty among older people in Switzerland and the U.S. National welfare states, in combination with advantages and disadvantages accumulated over the life courses, and statuses such as gender and ethnicity, shape the types of economic deprivation that older people can face. In addition, support from private and public organizations (here after 'social organizations') and the social environment (family, neighbors, and friends) is often critical for older populations--something that the recent pandemic has greatly brought to light. Some authors additionally point to the influence of the geographic environment on the living conditions of older people. However, existing analyses give little attention to the experiences that poorer older people have of poverty, particularly in rural areas. And yet, poorer older people's experiential knowledge, i.e., knowledge they acquired by experiencing poverty themselves, could contribute to a better understanding of poverty in later life in rural context, and of what could improve poorer older people's lives. The present research project addresses these gaps by exploring the experience of poverty among older people living in the Swiss alpine canton of Valais and the Appalachian region of Virginia in the U.S. These regions represent interesting settings for our purpose as they are both economically deprived areas within rich countries, they are located in rural and mountainous territories, and the percentage of older people in these areas is high compared to the national average. At the same time, they differ on one major aspect: old age and health welfare policies are more generous in Switzerland than in the U.S. Our research is based on qualitative semi-structured interviews with 70 poorer older people. It explores the economic and social constraints and resources that shape these people's living conditions in these areas. By doing so, based on interviewees' experiential knowledge, it seeks to provide a better understanding of the influence of welfare states, social organizations, the social environment, and life course major events on deprived older people's living conditions in rural areas. It will also pay attention to the role of social statuses (particularly gender and ethnicity) in such contexts. While this research project is not about the Covid-19 pandemic, it will take place in a post-pandemic world, and the social and economic impacts of the Covid-19 crisis will likely shape the results.This research project will provide us with an in-depth and broad understanding of the constraints and the resources that shape the experience of poverty in later life in rural contexts and bring to light forms of poverty that may not appear in existing statistics. The results will bring new knowledge about how poorer older people deal with their situation, and give the possibility to compare policies, programs and services that work for them--or do not work so well, some of which may be inspiring for other similar contexts. It will also suggest new ways of better supporting people experiencing economic deprivation in later life, in such areas as Valais and the Appalachian region of Virginia, and elsewhere.",,2026,Institut Travail Social HES-SO Valais/Wallis,601936.39,Human Populations,Unspecified,Older adults (65 and older),Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2023 +P28522,206160,New Evidence on the Role of Financial Advice,"Financial decisions are among the most important decisions households have to make. When making these decisions, a large fraction of households rely on financial advice. In this project, we aim at better understanding the role of financial advice in three different contexts. All three subprojects are of empirical nature and use anonymized data on retail investor trading activity and financial advice from a large Swiss bank.First, we will analyze the impact of financial advice on retirement savings. In past decades, many countries have reformed their pension system such that the responsibility for income during retirement is at least partially transferred from the state to individuals. A strong dependence on personal retirement savings makes people financially vulnerable and many retirees state that they wish they had saved more money for their retirement. We will analyze whether and how financial advice can help individuals to better prepare for retirement. In doing so, we will put a special focus on groups that have been shown to be particularly prone to undersaving for retirement, such as women, poorer individuals, and less educated individuals.Second, we plan to investigate whether and how financial advice can help investors to cope with crises situations. Specifically, we will use the recent COVID-19 crisis to investigate whether and how financial advisors help their clients to avoid panic and irrational behavior in times of increased uncertainty and anxiety. More specifically, we will examine how bank clients traded during the crisis, whether they sought and traded more or less on advice, whether financial advisors provided more or less advice, and how valuable this advice was.Third, we aim at better understanding the role of compensation structures for financial advisors. Particularly, we will investigate how a ban on payments from product providers to financial advisors (so-called kickbacks) affects the quality of financial advice. Kickbacks may result in biased financial advice as they incentivize advisors to recommend the products that pay the highest kickbacks rather than the products that are most suitable for the clients. To comply with new regulations in Switzerland and the European Union, the bank from which we obtain the data switched from a commission-based to a fee-based model of financial advice in January 2018 and since then forwards all payments it receives from product providers to its advised clients. We will first investigate how this de facto ban on kickbacks affected the profitability of different products from the bank's perspective. We will then analyze whether and how the recommendations of advisors changed around January 2018. Finally, we will investigate whether the quality of advice improved following this ban on kickbacks.In summary, our project advances our understanding of the role of financial advice in financial markets and informs about potential benefits and costs associated with seeking and providing financial advice. Results of this project will not only be relevant for researchers, but also policymakers, financial institutions, and the broader public.",,2025,Swiss Institute of Banking and Finance University of St.Gallen,196776.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2023 +P28523,196387,A multidisciplinary approach to identify vulnerabilities of SARS-CoV-2 for vaccine development,"The newly discovered coronavirus (CoV) SARS-CoV-2 is responsible for the recent pandemic outbreak of pneumonia that threatens countless lives across the globe. Like all viruses it critically relies on the reprogramming of the cellular metabolism and in particular on hijacking the translation machinery of its host. The goal of this proposal is to identify vulnerabilities of the virus during its usurpation of the host cell. Specifically, we will comprehensively test multiple aspects that SARS-CoV-2 may use to hijack host translation. This will be crucial to design attenuated viruses that can be used as vaccines not only for this virus but also for newly emerging zoonotic viruses in the future.Therefore, we will first, ask whether the virus hijacks the host RNA modifications machinery to modify its own RNA genome to avoid detection by the host cell innate immune defense systems. Second, we will identify the host RNA modification machinery that mediates the modification of the viral genome. Third, we will examine whether viral RNA modifications facilitate the recruitment of the host translation machinery. To this end we will use ribosome profiling and RNAseq in a high-resolution infection time course to quantitatively determine the translational response of the host cell. This will reveal how SARS-CoV-2 exploits the mRNA translation machinery of the host during its life cycle. Fourth, we will test whether the virus modulates the levels of tRNA and tRNA modifications to achieve efficient translation despite the diverging codon usage between its genome and the one of its host. Finally, we will apply the knowledge gained to develop synthetic attenuated viruses lacking RNA modifications or containing sequence elements that are difficult to translate during an infection. We will test select viruses by ribosome profiling and in infection experiments. By combining these approaches, we will identify how SARS-CoV-2 interacts with its host and in particular its translation and RNA modification machineries. This will identify drug targets & strategies to rationally design attenuated viruses that can be used for vaccine development.This proposal assembles an interdisciplinary team by joining the forces of three labs that combine expertise in diverse areas like molecular virology of coronaviruses, translation mechanisms (including that of viral RNAs) and of RNA modifications. Importantly, this will allow us to go beyond the current state of the art. In particular since this team has direct access to live virus samples and the ability to create recombinant SARS-CoV-2 for experimentation. We are confident that the combined knowledge generated on this new virus can rapidly facilitate vaccine development.Importantly, we will make our initial ribosome profiling data available immediately after its acquisition to speed up research during this ongoing crisis.",,2020,"Departement für Chemie, Biochemie und Pharmazie Universität Bern",463300.25,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis | Pre-clinical studies",2020 +P28525,198415,"Canakinumab in Patients with COVID-19 and Type 2 Diabetes: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial","Rationale:Patients with a metabolic syndrome (overweight, diabetes, hypertension) have a particularly bad outcome if infected with covid-19. This may be explained by an over-activation of the IL-1beta System. Indeed, metabolic stress (increased glucose and lipid levels) induces NLRP3-mediated IL-1beta secretion. Covid-19 also activates NLRP3. Therefore we hypothesize that metabolic stress in patients with overweight and diabetes potentiates covid-19 induced hyper-inflammatory syndrome leading to excess mortality in these vulnerable patients.Backrgoung:Activation of the innate immune system by IL-1 is apparent at all stages of the development of obesity associated type 2 diabetes and its complications. This includes impaired insulin secretion and sensitivity, cardiovascular diseases and heart failure. Accordingly, IL-1 antagonism has been shown to improve glycaemia, cardiovascular complications, and to reduce hospitalization for heart failure and heart failure-related mortality. The latter is of particular importance in the context of Covid-19, because patients with type 2 diabetes per se are at high risk to develop heart failure with a high mortality rate. Several studies have shown that the corona virus stimulates the NLRP3 inflammasome leading to a severe inflammatory response by the IL-1beta pathway, as reflected by CRP and IL-6 increase. In obese diabetic individuals, metabolic stress also promotes the IL-1ß pathway. Thus we hypothesize that both mechanisms will synergize leading to a deleterious hyper-inflammation as often observed in obese diabetic patients affected by Covid-19.Our hypothesis is supported by several recent studies. Indeed, in a cohort of >7'000 Covid-19 patients, type 2 diabetes was associated with a higher death rate. Supporting our hypothesis that glucose-induced IL-1ß will amplify Covid-19 hyper-inflammation, hyperglycemia correlated with a worse outcome. Most importantly, in a retrospective cohort study of patients with Covid-19, treatment with the IL-1 receptor antagonist IL-1Ra was safe and associated with clinical improvement in 72% of patients.Method:This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in hospitalized patients with COVID-19 infection and type 2 diabetes.A total of 116 patients will be randomized using a 1:1 allocation ratio of which 58 subjects will receive a single intravenous canakinumab infusion and 58 patients will receive a single placebo infusion.",,2022,"Klinik Endokrinologie, Diabetologie und Metabolismus Universitätsspital Basel",475990.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Clinical trial (unspecified trial phase),2020 +P28528,209947,"Boosting Public Discourse: Towards a Targeted, Evidence-Based Strategy to Improve Moral Reasoning","Background and rationale The public discourse on Covid-19 and its shortcomings have highlighted the importance of a clear and consistent usage of moral key terms that have practical implications for pandemic management. Diverse understandings of terms such as 'autonomy', 'freedom' and 'dignity', 'justice', 'solidarity, 'responsibility' and 'proportionality' have shaped how pandemic measures have been received by individuals and social groups. For instance, the concept of solidarity has been invoked to justify equal access to treatment notwithstanding vaccine status, while it has also been argued that the lack of solidarity shown by those who refused vaccination for non-medical reasons justified posteriorizing their care in case of scarcity. Whereas mutual accusations of moral failure will only lead to polarization, an exchange on the meanings and potentially shared understanding of terms such as solidarity might lead to a more constructive public discourse and, eventually, to greater societal resilience to severe crises. Overall objectives and specific aimsOur project intends to a) contribute to a better understanding of how public discourse may fail due to an unreflective use of moral key terms and b) probe a strategy for improving readiness for public discourse through a well-reflected use of moral key terms. Specifically, we aim to 1) analyze and map how moral key terms are used and comprehended in pandemic-related public discourses, performing a detailed analysis of press releases from the government, media outlets, social media, and focus groups with populations less vocal on social media; 2) provide a philosophical analysis of common conceptual and argumentative pitfalls regarding the use of moral key terms in public discourses; 3) develop and pilot-test an innovative gamified intervention that empowers users to reflect on their understanding of moral key terms and to train their clear and consistent use in moral arguments; 4) devise an evaluation strategy for interventions aiming to improve moral reasoning skills as an important element of readiness for public discourse. Methods and expected results The project will combine components of text mining and natural language processing, discourse analysis, philosophical analysis and qualitative methods (vignette-based interviews, focus groups). The expected results include an account of common pitfalls in the use of moral key terms in pandemic-related public discourse; a pilot-tested gamified intervention aiming to help avoid those pitfalls; and a strategy for evaluating the impact of the game (and possibly similar projects) on users' readiness for discourse. Potential impactEmpowering citizens, particularly the young generation, to engage constructively in high-quality public discourses will facilitate the search for the best actions to take in times of crisis, increase the democratic legitimation of measures and strengthen societal resilience and cohesion.",,2026,Institut für Biomedizinische Ethik und Medizingeschichte,519285.87,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Policy research and interventions,2023 +P28531,208386,Pandemics & Bioethics: Co-Designing a Graphic Novel,"The recent pandemic has shown us, on a large scale, that bioethics is much more than a field of theoretical research. Leaders had to make numerous difficult decisions at the political, health and economic level, which strongly impacted both society and individuals. We as bioethics scholars must better understand the need, role and performance of ethical decision-making tools and bioethics reference frameworks that are designed to help decision-makers form well-reflected and well-justified choices to benefit society as a whole. But just as importantly, we need to help citizens understand key bioethical concepts so they can engage in a constructive, nuanced public discourse on the management of the current and potential future pandemics or other public health crises to foster societal resilience.Our project, 'Pandemics & Bioethics: Co-Designing a Graphic Novel', aims to document, illustrate and communicate bioethical concepts in the context of the COVID-19 pandemic to better prepare ourselves for similar situations that are bound to occur in the future. The project will inform and encourage a mutual instructive and educational dialogue surrounding several bioethical challenges caused by pandemics while using the current pandemic as a starting point. The goal is to co-create a graphic novel to provide a defined audience - Generation Z - with a clearer understanding of these central bioethics concepts relevant to pandemic management. To do so, we will create spaces for dialogue between our researchers, a graphic designer and user groups. We will then use this dialogue to co-design key messages and storyboards and test them with users. This process will be part of the communication project before leading to the final product (i.e., the graphic novel).We will base the graphic novel and the dialogue on the latest research from the University of Zurich. The team at our institute - the Institute of Biomedical Ethics and History of Medicine - has published peer-reviewed articles on pandemic-related topics such as: ICU triaging, vaccine allocation, self-experimentation, preventive measures, access to health care and economic implications, dealing with the anti-vaccination community, information needs, as well as risk and crisis communication.We strongly believe this research needs to be shared with a larger audience since data suggest COVID-19 may not be the last pandemic we will experience. Using this research, we will set up a dialogue component using mini-publics. A mini-public refers to ""an assembly of citizens, demographically representative of the larger population, brought together to learn and deliberate on a topic in order to inform public opinion and decision-making"" (Escobar 2017). Members of Generation Z, the target demographic we have chosen for the mini-publics, together with a designer, our researchers and assisted by a facilitator will create a dialogue surrounding these topics, which will serve as a basis for the co-designed graphic novel.",,2025,Institut für Biomedizinische Ethik und Medizingeschichte,203496.67,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Clinical and Health System Decision-Making | Community engagement | Communication,2022 +P28532,195905,PubliCo - an experimental online platform for COVID-19 related public perception,"As the Corona Virus (SARS-CoV-2) continues to spread globally, causing severe human disease and death (COVID-19), citizens around the world have been exposed to crisis communication from a diverse spectrum of media outlets, including websites of public health authorities and universities, newspapers, television broadcasts, and social media platforms. These policy briefings, expert opinions, popular sentiments as well as dashboards, interactive maps and visuals, have not only become sources of information but also an incubator for emotional responses, moral judgements, and behavioral changes in daily routines, during a public health emergency. Clearly, not all communication content is equally reliable and citizens vary in the information sources they can or choose to access. Providing high-quality information while actively dismantling myths is a key concern for national and global health authorities, as exemplified by the Swiss Federal Office of Public Health (FOPH) and the World Health Organization (WHO) information campaigns. These efforts, however, need to be complemented by endeavors to obtain an excellent grasp of public perception in order to allow for continuous adaptations and improvement of emergency communication strategies. Failure to communicate effectively might result in irritation, loss of trust, and suboptimal adherence to public health policies. Against this backdrop, our project aims to develop a tool that helps tackle the ""infodemic"" manifested in the COVID-19 context, with a focus on a nuanced and in-depth understanding of public perception. With this tool, we aim to foster effective and tailored risk and crisis communication as a precondition for ""combating mis-information, stigma, and fear"" (cf. call text). We will address this challenge along three lines of work:1.Establish PubliCo - an experimental, interactive online platform collecting data on public perception of COVID-19 and its implications, as a feedback loop for policymakers, health authorities, experts and media professionals engaged in providing information to the Swiss public. 2.Design and apply toolkits to assess emotional state, behavioral dispositions, changes in social practices, and moral preferences of the public (e.g., regarding restrictive measures or resource allocation issues). 3.Develop an ethical framework for public health crisis communication, including ethical criteria for ""good"" communication, preconditions for trust, cooperation and responsibility, as well as the role of public preferences in relation to policymaking and crisis management. The project adopts a trans-disciplinary multi-stakeholder approach including a participatory citizen science component. Methodologically, we propose a combination of literature review and analysis, and empirical studies using mixed methods. Building on real-time data and continuous data collection, our research results will be highly adaptable to the evolution of the current emergency (e.g., with respect to new drug or vaccine). As regards research outcome, we expect the tool to be readily translatable to other public crises, such as disaster management, refugee crisis, and other public safety and civil protection scenarios, where national and international authorities will need to grapple with the development of crisis communication strategies to address public needs and interests.",,2022,Institut für Biomedizinische Ethik und Medizingeschichte,308880.56,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Communication,2020 +P28533,196615,Mixed-method evaluation of an online forward triage tool within the COVID-19 pandemic,"The overall purpose of the study is to estimate the effects and assess the utility of an online forward triage tool (OFTT) in epidemic or pandemic situations. We propose a mixed-method sequential explanatory study of the utility and effects of an OFFT for COVID-19 in Switzerland.The current outbreak of the novel Coronavirus termed SARS-CoV2 will likely last for several more month at least and will most likely outrun the capacity of most health systems internationally. Governments worldwide respond with frequently changing policies and guidelines, resulting in uncertainty among the public and health care providers alike. Next to caring for the sick, the health system is thus currently burdened with a large number of persons seeking information, testing and reassurance. When presenting in person, these people put themselves at risk of cross infection and further burden the health systems capacities.In response to this situation, we developed an online forward triage tool (OFTT) to i) screen and reduce the number of people presenting themselves for testing on site that do not fulfil current testing criteria and direct them to the appropriate level of care, ii) provide a reliable and up to date source of information about testing and reporting criteria to both, the public and health professionals, and iii) monitor temporal and regional patterns in testing recommendations and provide authorities with data on the effects of changes in testing criteria and guidelines. Many other providers have set up similar tools. However, it is not clear whether users of an OFTT actually follow the recommendations given and what factors affect their decisions. In addition, it is unknown whether the recommendations given, although based on the most current FOPH testing criteria, are in fact correct. Arguably, the use of an OFTT is only defensible if users have better or at least similar outcomes than non-users. Furthermore, it is unknown whether OFTT appeal to all population groups. For example, the elderly may be less inclined to use online tools to guide their decision making. Likewise, education or socio-economic status may affect whether users turn to an OFTT and to what extend they rely on the tools recommendation. In addition, it is unknown how far people's use of OFTTs is affected by media coverage of a pandemic or epidemic.We propose a mixed-method sequential explanatory study of the utility of the OFTT and the outcomes of using such a tool. Based on large data sets already collected at both, the first OFTT for COVID-19, and the currently largest real-world testing site in Switzerland, we will conduct a survey of users who provided contact details for research purposes. Results of this survey will inform qualitative data collection. In addition, at the synthesis level, quantitative findings will be understood and explained with the aid of qualitative results. Insights gained will be used in the adaptation of existing OFTTs. Findings from this research will result in rapid implementation and the improvement of existing OFTTs with regard to i) user groups reached and not reached, ii) improved adherence to recommendations, iii) easing the burden on the health care system and iv) their ability to inform authorities about the effect of changing testing recommendations.",,2022,Universitäres Notfallzentrum Inselspital Universitätsspital Bern,102863.4,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Digital Health,,,Switzerland,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P28534,204011,Against Structural Postponement: On the Legitimacy and New Possibilities of Sharing,"The COVID-19 outbreak upturned the lives of hundreds of millions in its wake. As the new virus continues to spread throughout the world it casts brutal light on societies' weak points and failings from structural racism, extreme wealth and income inequality to the rejection of scientific analyses, and the deterioration in the quality of public discourse. This time of overwhelming disruption, however, opened spaces for ideas for change and hopes for improvement of institutions of solidarity and common sociality. The upheaval created by COVID-19 have brought forth new (and old) demands for fairer ways of measuring and acknowledging value creation and contributions to social wellbeing in society. In fact, finding ways to share risks and burdens more equitably and equally in an economically and ecologically entangled and interdependent world seems more than ever imperative for a viable future. This workshop takes as a starting point that institutionalized obligations of (re-)distribution and the scope, reach and reliability of them are not self-evident. With whom we share what, when and for what reasons is socially negotiated; it is a learned practice that is contingent on the systems through which societies order their relations to resources and objects of value, and the existing institutions of (re-)distribution and social welfare (Bear & Mathur 2015; Eckert 2019; Ferguson 2015; Muehlebach 2012; Mugler et al. forthcoming; Widlok 2017). These are contested; when events make visible how existing arrangements jar with factual interdependencies, they are more likely to be perceived as unjust, and demands for alternative institutions may arise (Eckert 2016; Eckert & Knöpfel 2020; Ferguson & Li 2018; Mugler 2019). With the rise of European and other Western nation states in the 19th century socially accepted obligations to share were increasingly conceptualized in relation to the people who lived in a demarcated territory (Beckert et al. 2004). The specific obligations that people had towards fellow citizens was dependent on the differentiation of citizenship - not all being equal, and not all having the same rights and obligations (Moyn 2018). The most drastic differentiations were for long drawn along race and gender, people of colour and women often having no political and economic rights, and different obligations than white men, and many systems for a long time also distinguished between classes, either explicitly or through the privileges awarded to private property (Pistor 2019). Moreover, people in colonial territories, despite belonging to the same jurisdiction, were only partially integrated into these long-term state organized solidary systems. Their common personhood was pre-dominantly not perceived as more significant than the differences in legal status, despite this being in tension with the universalistic traditions of Christianity or the liberal Enlightenment movement and their emphasis on civil and human rights with which colonialism often justified itself. While there have been advances towards more status equality, recognition of common humanity and reduction of extreme levels of poverty since then, the effects of the COVID-19 pandemic is an agonizing reminder that current institutionalized re-distributory systems are not preventing exploding levels of material inequality worldwide. The crisis hit us all, but those with the least economic rights and power- the poor often being in the majority black and minority ethnic communities around the world-experience the most impact: from the risk of exposure, the severity of infection and scale of the loss of life, to the shattering economic consequences of lockdown measures (UNDP 2020). The pandemic brings globally organized and enforced material inequalities into sharp focus and also documents domestically constituted and structured levels of distributional inequalities that are only to a limited extent transnationally produced and determined (Piketty 2020). This workshop takes the current enhanced visibility of the hierarchical ordering of people within and between states, and the concern and sensitivity for more equitable societies as a starting point for a debate on the legitimacy and concrete possibilities of new standards of sharing. We want to focus the debate on how to overcome the seeming contradictions between domestic and international solutions to problems that entangle these dimensions inextricably. We invite workshop participants to tackle this large question from the following three angles:a.Global economic interdependence and persistent national organization of redistribution We are interested to explore the history of the discrepancy between different fields of international norms. How exactly did distributional norms (tax & social policies) remain far less internationalized than trade, investments or human rights norms? Who are the different actors and institutions that continuously work to either overcome jurisdictional limits, or actually to disentangle states in terms of distribution in the age of global value chains, capital mobility and more generally increasing economic and ecological interdependence? How do their different projects ""assemble"" to bring forth particular regulatory assemblages in which certain fields are increasingly transnationalized, norms pertaining to natural or legal persons, while in other fields, jurisdictional boundaries determine rights and obligations? b.Visions of global egalitarian reformWe ask: what are the ""social lives"" of proposals, that reject the assumption that each nation state is accountable for economic justice on its own because of an assumed ""natural limitation"" of solidarity to established social groups, and which conceptualize institutionalized long-term obligations of sharing beyond national terms? What happened to the global welfare ideas of the leaders of independence that proposed to counter the wealth disparity at the level of nations a ""New International Economic Order"" during the decolonization of the world in the 1960/70s? Or to the suggestions from activist groups and scholarship that proposed global re-distributory tools (Tobin or Global Wealth Tax) to moderate the effects of financial deregulation and reverse wealth concentration by constraining the income of top-earners and global players? Where are these proposals that have a less state centred image of the world still ""alive"" and in which contexts do they currently (re-)emerge (Temporary Basic Income, ""TBI"")? c.National and transnational orientation of demands for more equitable societies Lastly, we want to explore how calls for more equitable societies confront the interdependence of transnational and domestic distributional inequalities, but also attend to their independence (Mugler 2019). How do cosmopolitan proposals, that envision extra-territorial obligations to promote global as opposed to purely national well-being, address unequal distribution levels within states? Demands to accept new global standards of sharing were historically repeatedly countered with the argument that such proposals overlook the blatant inequalities in wealth that were evident in post-colonial states themselves. Moreover, how do current proposals that fight for more equal distributive justice in specific bounded states account for that their governments have no responsibilities to individuals outside their own jurisdiction? Especially, when distributional inequalities in their territory or elsewhere are increasingly globally produced, because international trade, investment, finance, taxation regimes constrain the political choices open to peoples and governments, therefore have a fundamental bearing on human welfare on a worldwide scale. What are turning points that precipitate a change in how various groups of people in specific settings perceive and understand the entanglement of global and domestic distributional inequalities, but also their independence?",,2021,Institut für Sozialanthropologie Philosophisch-historische Fakultät Universität Bern,18360.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Economic impacts,2021 +P28542,202939,The implications of the Covid-19 crisis for smart city technologies in Central Asia,"In the context of the Covid-19 pandemic, we are witnessing an unprecedented proliferation of smart city technologies to tackle the spread of infectious diseases. While some governments in post-Soviet Central Asia (defined as including Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) already use smart city innovations to assist in policing urban areas (Marat and Sutton 2020), some of these technologies have been adapted to tackle the spread of Covid-19 and enforce quarantine measures.While surveillance systems are valuable tools to combat the virus, regional security scholars are worried about the extent to which smart city technologies deployed against the virus are becoming normalized and part of everyday law enforcement and governmental practices (Marat 2020). They fear that some autocrats will use the war on Covid-19 as an excuse to silence dissidents and extend their personal rule. As the example of China shows, advanced facial recognition software in smart cameras can be misused for racial profiling of ethnic minorities, such as the Uighurs (Deibert 2020).There is little research to date assessing and documenting the extent to which the current pandemic is fueling the spread of smart city technologies across Central Asian countries. Nor is there any research so far addressing the question as to if and how authoritarian regimes in Central Asia make use of smart city innovations to suppress political opponents, nor any studies into the wider Central Asian public's attitudes towards smart city technologies. My postdoc project is designed to address these deficiencies for Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan.Methodologically, this project will evaluate WVS 7 survey data, expert interviews, analysis of local smart city policies, along with digital city maps in ArcGIS, mapping the scale of smart city installations in the Central Asian cities of Almaty, Bishkek, Dushanbe and Tashkent. The study will make an innovative interdisciplinary contribution to both political science and surveillance studies and will set the framework for a more extensive research programme investigating how pandemics affect governance worldwide.",,2023,OSCE Acadmy in Bishkek,118332.05,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Kyrgyzstan,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2022 +P28543,222076,The implications of the Covid-19 crisis for smart city technologies in Central Asia,"In the context of the Covid-19 pandemic, we witnessed an unprecedented proliferation of smart city tools to tackle the spread of infectious diseases. Whereas facemasks have disappeared, smart surveillance technologies, such as CCTV cameras with integrated facial recognition software have become part of everyday law enforcement and governmental practices everywhere. As such the preliminary fear among surveillance scholars that the global health crisis has been used by governments around the world - and authoritarian-leaning regimes in particular - to normalise mass surveillance and expand their control over the population has proven to be spot on.Thus far we know little about how the pandemic has shaped the use of smart city technology by non-democratic regimes to monitor their citizenry. My SNSF project seeks to fill this void by examining the implications of the Covid-19 crisis for smart city initiatives in the authoritarian states of Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan.With respect to methodology, the project is carried out through the combined use and analysis of survey data, individual and focus group interviews with the wider Central Asia public, and local smart city policies, along with visual documentation of smart city installations in the Central Asian cities of Almaty, Bishkek, Dushanbe and Tashkent. The research makes an innovative interdisciplinary contribution to both political science and surveillance studies.",,2025,"Technology and Governance Humanities, Political and Social Sciences Federal Institute of Technology (ETH)",132725.47,Other,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2024 +P28544,212240,Beneficial and harmful long-term consequences of COVID-19,"Beneficial and harmful long-term consequences of COVID-19Background. There is considerable interindividual heterogeneity in human T and B cell effector responses, which can result in pathogen clearance and immunological memory or in immunopathology. The role of infection history in shaping different immune cell compartments is increasingly appreciated, although many aspects are still unclear in humans. Moreover, the effects of infections that generate strong systemic inflammation - such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - on T and B cells specific to other pathogens, autoantigens, and allergens is even less well understood.Hypothesis. We surmise SARS-CoV-2 infection generates immunological memory across different compartments, with compartment-specific phenotypical and functional features. Furthermore, we hypothesize acute infection will also impose an expansion-contraction dynamic on previously established memory populations, albeit to a lower extent than in SARS-CoV-2-specific T and B cells, thus resulting in shifts of T cell receptor (TCR) and B cell receptor (BCR) repertoires. We suspect that similar changes affect autoreactive and allergen-specific T and B cells and that such changes might be prominent in a subset of individuals with post-acute coronavirus disease 2019 (COVID-19) syndrome ('long-Covid').Aim 1: Characterization of SARS-CoV-2-specific T and B cells across different tissues. We have recently investigated SARS-CoV-2-specific T cell immunity in our COVID-19 cohort, which comprises 175 individuals followed up until one year after acute infection (Adamo et al. Nature 2022). In this proposal, we will assess SARS-CoV-2-specific T and B cell responses in blood, tonsils, and skin biopsies by using spectral flow cytometry, single-cell RNA sequencing (scRNAseq), and imaging mass cytometry. This comprehensive characterization will address important outstanding issues of long-lived memory cell distribution and phenotypes across lymphoid and non-lymphoid tissues.Aim 2: Effect of SARS-CoV-2 infection on pre-existing memory T and B cells. In our well-characterized COVID-19 cohort, we will assess the impact of SARS-CoV-2 infection on pre-existing memory T and B cell populations. To this end, we will perform spectral flow cytometry analysis and scRNAseq along with TCR and BCR sequencing, probing epitopes derived from common human pathogens such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and influenza A virus (IAV). Combining these approaches, we will estimate the dynamics and sizes of CMV+, EBV+, and IAV+ memory T and B cells during and after COVID-19 and observe changes in phenotype and transcriptome of memory cells, including bystander T and B cell activation and shifts in TCR and BCR repertoires.Aim 3: Effect of SARS-CoV-2 infection on autoreactive and allergen-specific T and B cells. We will investigate the effect of COVID-19 infection on autoreactive and allergen-specific memory T and B cells. Thus, we will adopt a similar experimental strategy to that described in Aim 2. Moreover, we will analyze these T and B cells in subjects recovering from COVID-19 compared to those with long-Covid.Expected results and impact. We will study the effects of acute infection on newly-formed and pre-existing memory cells, thus gaining insight into the dynamics of longevity, expansion and attrition of immunological memory. Furthermore, we will assess the impact of acute infection on autoreactive and allergen-specific T and B cell repertoires. Together, these findings will inform on the long-term beneficial and potentially harmful consequences of a natural acute infection in humans.",,2025,Klinik für Immunologie Universitätsspital Zürich,757142.86,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2022 +P28545,198431,Correlates of protective immunity to SARS-Coronavirus 2,"Correlates of protective immunity to SARS-Coronavirus 2Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the acute illness termed coronavirus disease 2019 (COVID-19). In light of the recent pandemic, a critical question relates to whether a primary SARS-CoV-2 infection leads to immunological memory able to confer long-term immunity to re-infection.Hypothesis. We hypothesize that protective immunity can form following SARS-CoV-2 infection, but its generation is influenced by disease severity (and thus antigen load) during primary infection. COVID-19 ranges from asymptomatic infection to patients developing severe pneumonia and acute respiratory distress syndrome. In our COVID-19 cohort (n = 181 as of 22 May 2020, recruitment ongoing), we recently found that SARS-CoV-2-specific IgA and IgG antibody responses correlated significantly with disease severity (Cervia et al. bioRxiv 2020). We submit that mild versus severe SARS-CoV-2 infection exerts quantitative and tissue-specific differences in T and B cell stimulation during primary infection, which in turn lead to significant qualitative differences in terms of protective long-term immunity.Specific aims. This hypothesis shall be tackled within the following two aims:Aim 1 - Primary SARS-CoV-2 infection: In our well-characterized COVID-19 cohort, we will assess the immune response to primary SARS-CoV-2 infection in mild versus severe COVID-19 cases. Using 80-parameter mass cytometry, we will characterize the ex vivo innate and adaptive immune response. 30-40-color spectral flow cytometry will enable us to study phenotypic and functional properties of SARS-CoV-2 peptide pentamer-specific CD8+ T cells, which will be complemented by single cell RNA sequencing and proteogenomic approaches. SARS-CoV-2-specific B cells will be assessed using enzyme-linked immunospot assays and flow cytometry. We will also determine SARS-CoV-2-specific IgM, IgA and IgG titers in sera and mucosal fluids and conduct SARS-CoV-2 neutralization assays to functionally assess these antibodies. Using SARS-CoV-2 peptides, we will stimulate antigen-specific T cells to assess their cytokine production, proliferation and cytotoxicity.Aim 2 - Immunity: We will determine the above-mentioned properties of SARS-CoV-2-specific T and B cells at 6 and 12 months after primary SARS-CoV-2 infection in our entire cohort. Moreover, we will monitor our cohort for clinical signs of upper respiratory tract infection and, if suspected, perform sampling of respiratory mucosa to assess SARS-CoV-2 by quantitative reverse-transcriptase polymerase chain reaction. In subjects with proven SARS-CoV-2 re-infection, we aim to sequence the viral genome for signs of immune escape and perform the aforementioned tests to elucidate the status of SARS-CoV-2-specific T and B cells. Lastly, by using computing-intensive mathematical algorithms, we will identify the kinetics and determinants of protective SARS-CoV-2 immunity.Expected results and impact. Our project will provide insights into the phenotypic and functional properties of SARS-CoV-2-specific T and B cells during the primary immune response and the memory phase in mild versus severe COVID-19 cases. By comparing these data with clinical correlates of mild versus severe COVID-19 disease as well as protection from a secondary infection with SARS-CoV-2, we will generate crucial knowledge on determinants of protective immunity, knowledge that will be instrumental for informing clinical diagnosis and care, vaccine development, and policy makers.",,2022,Klinik für Immunologie Universitätsspital Zürich,961983.05,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Disease pathogenesis,2020 +P28551,198052,The Zurich Project on the Social Development from Childhood to Adulthood: Phase VI,"The Zurich Project on the Social Development from Childhood to Adulthood (z-proso) is a prospective-longitudinal study of a cohort of 1'675 children who entered one of 56 public primary schools in Zurich, Switzerland, in 2004. The aim of the study is to understand the processes that influence multiple domains of development from childhood to adulthood (e.g., social development, violence/crime, psychopathology). Data from participants were thus far collected at ages 7, 8, 9, 11, 13, 15, 17, and 20. Currently spanning 14 years, at a relatively fine-grained time-resolution, z-proso is one few contemporary long-term longitudinal studies from childhood into the young adult years in Switzerland, and internationally. Constructs measured at each z-proso assessment include prosocial behavior, aggression and violence, internalizing problems, substance use, ADHD, non-aggressive conduct problems, and delinquency. Recently, z-proso also coded records on participants' contacts with the youth justice authorities as either victims or perpetrators to age 18. Additionally, z-proso has collected detailed information on putative mechanisms in development, including at the individual level (e.g., self-control, sensation seeking, cognition and decision-making), the family level (e.g. parental involvement and monitoring, corporal punishment, sibling violence), the peer level (e.g., relationship quality and best friends' delinquency), the school level (e.g., school commitment, relationship with teacher) and the neighborhood level (e.g., ethnic heterogeneity). In the initial phase the project also included a cluster-randomized universal intervention component. In 2017, z-proso became a national research infrastructure project. In addition to completing two major data collections (one from participants, one from juvenile records), the z-proso study since expanded its national and international reach, for example, via the z-proso International Research Network (zIReN). In addition, z-proso secured generous additional funding both within and outside University of Zurich to support its activities and to broaden the study's profile. For example, several z-proso add-on studies collected at, or after age 20, resulted, for example, in experience sampling data that capture psychological states of z-proso participants at the daily level and multiple levels of biological data (e.g. on gene expression, stress and sex hormones, brain activity, and substance use metabolites). These can now be examined in conjunction with the rich z-proso database. Starting in April 2020, z-proso also started a multi-wave, closely-spaced, data collection of participants' well-being during and after the COVID-19 lockdown.The current proposal outlines plans for z-proso to continue as a national research infrastructure for the 2021-2024 period. Specifically, the study will conduct a data collection with participants at age 24, and also a comprehensive collection of official data recorded by prosecution authorities during participants' young adult years. We propose several research priorities for this new funding cycle, including 1) Pathways into and out of Crime, 2) Developmental Psychopathology and Comorbidity, 3) Legal Socialization, Legitimacy, and Extremist Beliefs, 4) Internalizing Problems, Self-Harm, and Suicidality, 5) Trajectories of Substance Use, Including Desistance, 6) Developmental Victimization, 7) Sequelae of the COVID-19 Pandemic, 8) Immigrant Well-Being and Delinquency, and 9) Life Events, Turning Points, Peers, and Romantic Relationships. The proposed continuation will further enrich our understanding of developmental dynamics from childhood to adulthood. It will also enhance z-proso's international prominence as a resource for understanding developmental pathways of young people. Importantly, z-proso has assessed children in the community since grade 1, and one of its great strengths is its rich data on young adults from all backgrounds. In the new funding cycle, z-proso will again be institutionally affiliated with the Jacobs Center for Productive Youth Development at the University of Zurich. The Jacobs Center is a world-leading interdisciplinary research institution devoted to studying the crucial transitions from childhood to adolescence and adulthood. Thus, it provides an ideal environment for z-proso as a showcase of high-quality social research in Switzerland.",,2024,z-proso Jacobs Center fPYD Universität Zürich,1125760.09,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Social impacts,2021 +P28561,214991,TRUST-ME: TRUstworthy enhancement of job SaTisfaction and productivity using Micro-sensing in work Environments,"For almost a century, employee productivity and job satisfaction have been a topic of interest. They are sometimes in conflict, with employers pursuing productivity at the expense of employee satisfaction. Other times they are aligned, as satisfied employees tend to be more productive, and employees that feel productive are usually satisfied. Over the years, awareness of the importance of good work conditions for physical and mental health has grown, and legislation to protect workers has followed. However, new concerns such as precarious employment (i.e., the ""gig-economy"") have also led to increased stress and worsened mental health among the workforce. Technology has seemingly tipped the scales the wrong way in recent years. Today, so-called ""technological supervision"" - the automated management of employee schedules, from warehouse staff to hotel housekeepers to software developers, in a quest to maximize efficiency - is increasingly creating physical and mental exhaustion among those managed in this way. The COVID-19 pandemic, with the increase in remote work, has only exacerbated these problems. There is thus a need for approaches that increase productivity, job satisfaction, and employee well-being without sacrificing one for the other.Recent developments in sensing technology (e.g., video- and audio-based and wearable sensors) and advanced artificial intelligence (AI) algorithms are promising personalized digital tools for monitoring well-being and boosting productivity. At the same time, awareness of privacy issues and the possibility of unpredictable and undesirable outcomes of AI have grown, prompting interest in the development of privacy-preserving technology and trustworthy AI. By combining expertise in sensing technology, privacy, user experience design, and explainable AI, this project will develop a new approach for monitoring job satisfaction, wellbeing, and productivity. The project will (1) offer insights into the complex relations at work in AI-driven privacy-aware workplace monitoring and (2) create powerful yet explainable AI that provides actionable productivity insights.The TRUST-ME project will utilize the expertise from two separate institutions. Swiss partner USI has expertise in security, privacy, and trustworthy AI. Slovenian partner JSI has expertise in machine learning for sensing and modeling psycho-physiological constructs, including employee wellbeing. The proposed project will thus explore the problem domain via two critical strands of investigation: (1) multimodal monitoring and modeling of job satisfaction and productivity (led by JSI) and (2) multimodal, secure, private, and explainable AI for productivity assessment (lead by USI). The first strand will employ physically unobtrusive workplace sensors for knowledge workers, such as computers (which can sense typing patterns, mouse movement, and application usage), cameras, and eye trackers. These will be used to obtain psychological constructs of interest, e.g., satisfaction, wellbeing, engagement, self-perceived productivity, and affect. We will model these constructs' interrelation using multi-modal sensor inputs and multiple sources of ground truth based on novel deep-learning methods involving deep supervision and bi-directional learning. This approach will represent the problem domain more accurately, alleviating the impact of noise in ground truth otherwise obtained via (subjective) questionnaires.The second strand will implement tools and techniques for maximizing user security and privacy in this context, including quality and integrity of data, access to data, and adequate privacy and confidentiality controls. We will use federated learning to build models on user-trusted local devices instead of sending potentially sensitive user data to a central location (where employers could misuse it). Additionally, we will develop multimodal explainable AI methods to provide transparency and end-user understandable reasons for the findings of the TRUST-ME models. We will exploit this to create a dashboard that will provide users with insights into their well-being and productivity while clarifying how the system came to these conclusions. Both employees and employers will receive information at the right granularity without intruding on employees' privacy. TRUST-ME will lay the foundation for future sensing interventions to improve job satisfaction and productivity while respecting ethical values such as privacy and autonomy. Both strands of the investigation will come together in a validation study with academic knowledge workers, software developers, and administrative staff. This study will provide inputs into the design of the TRUST-ME approach, data for training and evaluating the machine-learning models, and feedback on the dashboard presenting their outputs.",,2026,Istituto del Software (SI) Facoltà di scienze informatiche,701702.43,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2023 +P28562,209867,"How Worldviews Shape Social Responsibility: Religious and Secular Narratives of the Body, the Virus, and the State in the Covid-19 Crisis","The project aims to answer the following central question: How do religious and secular worldviews affect compliance and noncompliance with institutionally defined standards of socially responsible behavior? Just a few days after the first laboratory-confirmed case of Covid-19 in Switzerland in February 2020, the Swiss Federal Council established rules aimed at curbing the spread of the virus (e.g., concerning vaccination, or the attendance of large gatherings). The aim of this project is to determine the role of religious and secular worldviews in supporting or hindering adherence to the rules installed. The respective worldviews address somatic aspects of the pandemic, including individual bodily freedom and the necessity of physical co-presence in religious gatherings and collective worship, relate to broader reflections on topics such as the meaning and status of health, sickness, medical science, in-group medical and spiritual care, individual risk, and social responsibility.",,2026,Institut für Religionswissenschaft Universität Bern,517969.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2023 +P28563,215788,Telling Death. Intergenerational meetings and citizen dialogues on funeral and mourning,"The Covid-19 pandemic has highlighted a range of issues relating to death and bereavement. Faced with social distancing and health prevention measures, many relatives were not always able to accompany the deceased or organize the funeral as they would have liked. In this context, both professionals - active in the mortuary and funerary sectors - and relatives had to show adaptation and inventiveness, by proposing, for example, to broadcast a last farewell to the deceased by videoconference. This health and social crisis has therefore mobilized emerging and new practices in the mortuary and funeral field; it has sometimes accelerated their implementation or highlighted them. A good number of these practices, such as everything related to the eco-funeral register (humusation, biodegradable urns, sustainability of graves and cemeteries), are still unknown to the general public, which only becomes aware of them when confronted with the death of a loved one and especially when organizing a funeral. Telling death is a project of scientific communication which aims to inform and sensitize the general public to these new funeral practices which have been observed for a few years in Switzerland. It aims to make more visible the actors involved in the treatment of the deceased, between the place of death and the burial ground, and to encourage debate between researchers and a diverse public on the links between the materiality of death, the action of professionals and the experience of mourning by relatives. To this end, five partners will propose to the public to engage in participatory communication processes based on two SNSF-funded research projects (Necropolis and No Lonely Deaths). Inspired by the research methodology developed and the results obtained, the first step will be to organize and record in the form of podcasts a series of intergenerational dialogues, moderated by the researchers, on the care given to a deceased person and on the mourning his or her relatives experienced. These podcasts will then be used to engage and debate with the public in three very different contexts: during a rich exhibition on the subject of death, organized by the PALP Village et Festival, which will take place in Bruson (Valais) during the summer of 2023; during a participatory forum and 'Death Walk' organized by the Commune de Chavanne-près-Renens with its inhabitants during the fall of 2023; during citizen debates organized by Connaissance 3 - the senior citizens' university of the canton of Vaud - during the year 2024. All of these encounters and dialogues will involve researchers from the Haute école de travail social et de la santé Lausanne (HETSL | HES-SO) and the ColLaboratoire of the University of Lausanne.The Telling Death project will socialize a large audience to the issues related to the funerary transition in progress and inform the public about actual and emerging practices in this field. It will also be an opportunity to evoke ancient skills that are on the verge of extinction or rituals from cultures far from our own; it will encourage debate on the importance of the link between the material conditions of death and the experience of mourning. The podcasts produced during this project will finally be made available to the general public on a dedicated website and may serve as didactic support in other contexts (universities, in the fields of health and social work in particular, death professionals, associations, schools, etc.).",,2025,Haute école de travail social et de la santé HES-SO,216723.3,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P28564,195922,No Lonely Deaths. Answering the Impact of the Covid-19 Pandemic on the Funeral Sector and the Bereaved Families,"The Covid-19 pandemic generates an unprecedented sanitary and social crisis. Numerous individuals are currently mobilized to respond to this crisis, among them actors of the funerary realm. Our former research work leads us to take into consideration the unique situation caused by this pandemic, as well as its consequences for this specific sector and for bereaved families, and to propose the present research project. This crisis is unprecedented, not only in terms of the foreseeable number of deaths, but first and foremost in terms of its repercussions on the overall number of deaths. It arises in a globalized world in which public health issues are problematized as risks and, at this time, handled through confinement measures. By contrast with a catastrophe or an epidemic in which both localization and timeline are more clearly readable, each death in Switzerland - as well as in any other State that is applying such measures - is concerned, not only those due to a specific event, in this case a virus. It is thus necessary to assemble available knowledge and to act as swiftly as possible to identify what differs and what is new in today's situation, in order to enable the different actors - public health authorities, professionals engaged in various sectors, volunteers - to rapidly seek answers and find alternatives to alleviate the difficulties, problems and questions they are inevitably facing.Consequently, the goal of the project consists in documenting as quickly as possible the reorganizations proposed by the funerary agents during the crisis, with regard to the constraints and obligations resulting from the management of the pandemic outbreak in three different countries: Switzerland, France and Italy. Moreover, the goal is to evaluate their impact on bereaved family members, and to analyze the potential creativity deployed in coping with this unprecedented situation. This project thus aims not only at understanding the crisis itself, but also its aftermath in the months that will follow, in order to document practices, resolutions, adjustments and probable conflicts in relation with these situations. An anthropological approach will be adopted, in accordance with the ethical principles observed in the discipline; it will be based on an ethnographic approach - observation, formal and informal interviews (on-line during the confinement period) - of the work done by professionals in funeral homes, crematoriums and cemeteries during the crisis; a series of interviews will also be conducted with family members confronted with adjustments to the funerals of their loved ones.The No Lonely Deaths project is founded upon the following hypothesis: according to the scope and length of this sanitary crisis, the consequences in relation with funerary matters will necessitate - and necessitate already - a collective and co-constructed answer that acknowledges and secures the professional interventions; the bodies' treatment in relation with the sanitary and social recommendations; the funerary rituals at the time of death and during the following months. Accordingly, the project is experimental and original, on at least two aspects: first, it collects first-hand data and questions them in real time while the crisis is occurring, notably with regard to ethical issues; second, it compiles new information based on concrete experiences that might help public health authorities and stakeholders to apprehend social issues and figure out solutions during a pandemic, especially for the funerary sector and bereaved families.",,2022,Haute école de travail social et de la santé HES-SO,331131.13,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Research to inform ethical issues | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Governance | Indirect health impacts,2020 +P28569,196203,Crisis Management of the Covid 19 Epidemic in coercive contexts,"The period from the outbreak of the first Covid19 diseases in China to the epidemic in Italy and currently also the drastically increasing number of reports of infected people in Switzerland lasted only 8 weeks. As a consequence, public life was drastically reduced, schools were closed and employees were recommended or ordered to work in their home office. One basis for these preventive measures was a high degree of flexibility of each individual and alternative forms of work and also alternate forms of care in society. Nevertheless, there are institutions that are reaching their limits and are neither able to maintain physical distance nor couldn't work without their employees. These are institutions with a governmental mandate, whose clients are in a total system, the coercive context in mandated settings. In particular, these are institutions of the prison system, therapy facilities, as well as care facilities for children and young people. Here, on the one hand, the possibilities of living in a distance are drastically restricted, the employees must already be on site due to the security aspect, and the possibilities for information and communication are also classically handled restrictively. In addition, these are per se vulnerable groups because of infectious diseases such as hepatitis and HIV occur 9 times more frequently than in the overall population. Nevertheless, the institutions of the justice system and of care in the area of children and young people have a duty of care and the statutory mandate to adapt life in a coercive context to the conditions in freedom, including the health care. (StGB Art. 75). The question that arises is:•How can prevention measures be implemented in closed coercive contexts?In order to answer these question, several institutions of mandatory context, will be examined in more detail by means of qualitative interviews with employees from: prisons, youth housing and therapy facilities as well as residential and work externalities. The aim of the study is to find out which strategies and measures have proven to be helpful in dealing with pandemics and crisis situations, so they can be managed better in the future.",,2022,Institut für Delinquenz u. Kriminalpräventio Departement Soziale Arbeit ZHAW,162370.03,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures","Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings | Approaches to public health interventions | Social impacts",2020 +P28576,196729,Acidic pH inactivation of SARS-CoV-2 in exhaled breath and expectoration (ApHiCoV),"Acidic pH inactivation is known to be effective against enveloped viruses, such as SARS-CoV-2, which exposed to a low pH will denature spontaneously. Similar to pasteurization, viral reduction by chemical treatment at pH ~< 4, is thought to be achieved by destroying the lipid envelope, which results in an effective inactivation of the viruses. Several previous studies, e.g. for avian influenza virus and Bovine diarrhoea virus , suggest an exponential decay of active virus titer, exp(-t/t), with mean lifetimes t = 3-4 minutes upon exposure to pH = 4 (i.e. titer reductions by 99 % after less than 15 minutes). Similar investigations for SARS-CoV-2 are still lacking. ApHiCoV will investigate the possibility to use gaseous acetic acid (CH3COOH) in room air, as an easy-to-apply measure, in order to lower the pH of exhalation aerosol, expectorated droplets and contaminated contact sur-faces, and thereby to effectively mitigate the risk of transmission of enveloped viruses such as SARS-CoV-2. To this end we will- determine the thermodynamics of airway lining fluid and mucus and molecular diffusion processes therein, in particular with respect to solubility and diffusivity of CH3COOH;- investigate the uptake kinetics of CH3COOH into airway lining fluid and mucus of micron-sized aerosol particles, millimeter-sized droplets and contaminated planar contact surfaces;- consider the buffering by ammonium (NH4+ ), i.e. its neutralization by CH3COOH in the exhaled or expectorated substance as well as the loss of ammonia (NH3) to the gas phase of the indoor air;- determine the kinetics of pH-change (within milliseconds to minutes) inside the exhaled aerosol particles and expectorated drops subject to CH3COOH in the indoor air;- identify the target pH, i.e. the optimum acidity between being most efficient in virus inactivation, yet still acceptable for the health of the exposed individuals;- determine the pH-dependent inactivation kinetics of SARS-CoV-2 in the acidified airway lining fluid and mucus.These investigations will be performed experimentally in due consideration of biosafety and by thermodynamic and kinetic modelling. Experimental work will include the investigation of CH3COOH uptake kinetics of droplets in the 1-35 µm size regime by means of an electrodynamic balance, a direct determination of droplet pH for these droplets, and the measurement of active virus titer reduction in acidified airway lining fluid and mucus in a BSL-3 laboratory. Modeling work will apply a state-of-the-art thermodynamic and kinetic model applied in spherical and planar geometry for droplets and contaminated contact surfaces. We aim at answering the following questions:- Can rapid SARS-CoV-2 inactivation by pH-reduction be reached by applying indoor CH3COOH below the legal permissible exposure limit for 8-hour work-shifts, i.e. at concentrations below 10 ppmv?- Can such a pH-reduction even be reached by applying indoor CH3COOH below the odor threshold of unacclimatized individuals of ~1 ppmv? - If the results of this investigation are encouraging, could gaseous CH3COOH be used as disinfecting measure in hospitals?- Given CH3COOH application would be a cheap and easy-to-apply measure, allowing the inactivation of viruses in exhaled aerosol, in droplets and on all kinds of surfaces, could it potentially also be applied in other places in the public domain or in private houses?",,2022,Climate Dynamics Group Institute for Atmospheric & Climate Science ETH Zurich,308460.34,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Infection prevention and control",Environmental stability of pathogen | Impact/ effectiveness of control measures | IPC in health care settings,2020 +P28588,208734,Immune repentance: forgiving the original antigenic sins of B and T cells,"Immune challenges, such as infections or vaccinations, result in the formation of immunological memory that can provide enhanced protection against future pathogen exposures. Diseases such as chicken pox or measles, for example, permanently shape the adaptive immune system and establish long-lived molecular recognition of the disease causative agents. However, in some cases, prior interaction with certain pathogens impairs the immune response mounted against genetically distinct strains. An individual's immune history, defined as the sum of all past and current immune challenges, contributes to the defense against future secondary immune challenges (e.g., reinfection). This concept, also referred to as original antigenic sin (OAS), has been traditionally described in the context of impaired protection against seasonal influenza infections, but has now emerged as a relevant consideration in both the global vaccination efforts against SARS-CoV-2 and reinfection with its evolving variants. For example, infection with H1N1 influenza strains has been reported to impact neutralizing antibody titers against future infections with genetically distinct influenza strains in mice and humans. These fundamental principles of OAS are relevant to the current SARS-CoV-2 vaccination strategies, as current vaccines use the genetic sequence of the spike protein derived from the original SARS-CoV-2 virus first detected in late 2019, despite increased prevalence and dominance of new variants of SARS-CoV-2 possessing mutations in their spike protein. This implies that future exposure of viral variants in immunized individuals may result in reduced vaccine efficacy and protection from infection. B and T cells play a crucial role in generating vaccine- and infection-mediated adaptive immunity and undergo a sophisticated generation and maintenance process termed clonal selection. B and T cells work together to produce high-affinity and virus-neutralizing antibodies, which are crucial to resolve infections. Understanding the molecular mechanisms underlying the selection of B and T cells is necessary to both profile how immune challenges permanently shape our immune system and how vaccines can be optimized to provide long-lasting and effective protection regardless of previously encountered immune challenges. Previous OAS studies have been largely based on population-level readouts from circulating serum, thereby ignoring the contribution of individual clones and the selective pressures which govern them. The selection of individual B and T cell clones, however, is what dictates the ability to generate broadly neutralizing antibodies against both previously encountered viruses and future unseen variants. It is therefore necessary to investigate how OAS imprints the adaptive immune response at the single-clone level to elucidate how vaccines confer broad protection against mutating viral populations. In this proposal, I will first investigate how immune histories alter the clonal selection of B and T cells during primary and subsequent immune challenges. A multidisciplinary approach of experimental and computational immunology methods will provide a mechanistic understanding of how OAS shapes the adaptive immune response at both the global and single-cell resolution. Second, I will use murine models of infection and immunization, transgenic mice enabling lineage tracing, and single-cell immune repertoire profiling, to further explore vaccination strategies that overcome the effect of OAS and achieve immune repentance of individual clones. Immune repentance refers to the molecular forgiveness of immune impairment resulting from previously encountered immune challenges. This will involve addressing how factors such as viral genomic sequence (e.g., SARS-CoV-2 boosters encoding either alpha, delta, or chimeric spike protein variants), dosing schedules, vaccination composition (e.g., protein vs mRNA), and heterologous vaccine administration routes (e.g., intranasal vs subcutaneous) interact with pre-existing B and T cell immunological memory. Finally, the elucidated molecular mechanisms underlying the clonal selection of virus-specific B and T cells from our proposed murine models will be investigated using human samples following SARS-CoV-2 infections and immunizations.",,2027,ETH Zürich Stabstelle Forschung/Wirtschaftskontakte,1042432.11,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P28591,221828,Superspreader: Pop culture and media discourses in the face of the pandemic,"This anthology traces an initial topography of pop culture knowledge about pandemics and their connections with the Covid-19 crisis in their media-discursive manifestations. Essays and academic discussions from the fields of cultural and historical studies, art, film and media studies, medical humanities, medical history and ethics, political and social sciences and public health approach the facts outlined from a theoretical, historical perspective as well as on a phenomenological level and thus offer a synchronous and diachronic view of epidemic and pandemic discourses, which shows that the epidemic has been present in all cultures for a long time and that, in the long term, the current corona pandemic is at best one chapter of many in the pop culture tradition of illness.",,2024,Institut für Biomedizinische Ethik und Medizingeschichte Universität Zürich,22476.97,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2024 +P28595,197721,Multi-omic analysis of anti-viral immunity: From relevant biological pathways to inborn errors of immunity in patients with severe viral diseases,"Viral infections remain a major threat for humankind with a number of alarming signs including 1) the limited effect or the absence of vaccines and/or efficient anti-viral drugs against a large number of viral infections, and 2) the recurrent emergence of new viral infections as attested by the recent pandemics of influenza viruses, Ebola virus, and coronaviruses with the current dramatic example of SARS-CoV-2 infection. In all these viral infections, there is a huge inter-individual variability in the response ranging from asymptomatic infection to lethal disease. In most cases, only a small proportion of otherwise healthy, young people develop the most severe forms of the disease, strongly suggesting the role of human genetic factors. We and others have already identified a number of monogenic inborn errors of immunity (IEIs) underlying life-threatening acute viral diseases, such as herpes simplex virus encephalitis (HSE), fulminant viral hepatitis, severe cytomegalovirus primary infection, and severe influenza virus or rhinovirus pneumonitis. However, most patients with severe viral infections have no identified genetic defects yet. In the present project, we hypothesize that severe viral infections such as HSE, and life-threatening pneumonitis due to influenza virus, rhinoviruses, respiratory syncytial virus, or SARS-CoV-2 infection in otherwise healthy individuals can be the consequence of a diverse collection of IEI to viruses, at least in a substantial proportion of patients. We further hypothesize that these IEI may affect specific pathways, and that the expression patterns of response to viral stimuli observed in a healthy population may inform on the involved pathways. To test these hypotheses, our project will tackle two specific aims: 1) to identify relevant pathways involved in the response to viral antigens using transcriptomic studies in an extensively studied cohort of 1000 healthy subjects; 2) to discover novel IEI underlying severe viral infections using next generation sequencing of the patients' exomes, bioinformatic analysis and in-depth functional studies of biochemical and immunological nature, by means of cutting-edge strategies we already developed in our previous identifications of IEIs that will be optimized by the findings obtained in specific aim 1. This highly innovative project is feasible based on the complementary and synergic expertise of the two participating laboratories, unique cohorts of patients, and strong preliminary results. The immunological implications of our project are considerable with the discovery of the critical pathways involved in the development of these severe viral infections, and the dissection of mechanisms of immunity to viruses in pulmonary and central nervous system infections. Our project will also have major medical implications by providing new tools for diagnosis and genetic counselling that may lead to specific preventive measures in the predisposed subjects, and by paving the way toward novel preventive and therapeutic strategies including anti-viral drugs (e.g. aimed at restoring a deficient immunity) and vaccines (e.g. aimed at boosting certain immunological pathways). Overall, our human genetic approach to discover IEI underlying severe viral infections, and consequently to understand the pathogenesis of these diseases, is critical to provide new ways to combat the current global threat of viral infections.",,2025,Global Health Institute EPFL SV-DO,749885.82,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2021 +P28604,205933,WISE: Wastewater-based Infectious Disease Surveillance,"MOTIVATION Infectious disease dynamics and drivers are primarily inferred from clinical case data. When there are insufficiencies in clinical data collection (i.e., limited testing), disease dynamics remain incomplete or unobserved. Examples include dynamics of disease with mild-to-moderate health impacts or with high rates of asymptomatic infection. Wastewater-based epidemiology (WBE) offers a complementary approach to track infectious disease dynamics independent from clinical surveillance. By tracking viral loads shed into wastewater by large populations within a catchment over time, we can infer and potentially predict previously unobserved epidemiological dynamics and their drivers.GOALS Here, we propose to advance the methods and analyses underlying wastewater-based infectious disease surveillance such that we obtain insights into the epidemiological dynamics of viruses beyond those achievable through clinical case surveillance alone. Specifically, our proposal will allow us to address the following THREE MAIN RESEARCH QUESTIONS:1) What drives the epidemiological dynamics of viruses? How early can viral outbreaks be detected and their future fate modelled based on wastewater analyses?2) Can we rapidly determine the genetic variants founding a wave? And can we determine the future fate of the wave based on wastewater data? 3) How does a pandemic virus transform into an endemic virus? To what extent can we predict its endemic properties?These research questions advance foundational, policy-relevant insights into disease trajectory that can help inform intervention strategies, and can not be addressed using clinical surveillance alone.RESEARCH APPROACH To tackle these research questions, we will advance and adapt our methodological approaches obtained during the COVID-19 pandemic to address SARS-CoV-2 disease trajectory. Specifically, we will extend our work to cover other priority pathogens (human coronaviruses, influenza, norovirus and other enteropathogens); improve methodologies for virus detection, quantification, and sequencing; advance methodologies for modeling and analyzing data to address epidemiology, and disseminate findings and methodologies to relevant stakeholders.IMPLEMENTATION The project will be led by Prof. Dr. T. Stadler, with expertise in infectious disease epidemiology, through collaboration with three other applicants with diverse expertise in the fields of environmental engineering (Dr. C. Ort), pathogen detection in the environment (Dr. T. Julian), and computational biology (Prof. Dr. N. Beerenwinkel). The project is organized by four distinct research work packages (WPs) that integrate to provide infectious disease data that is unattainable without the proposed interdisciplinary approach. Specifically, WP1 (Characterizing catchment properties) and WP2 (Methods for virus detection) advance methods to characterize virus shed in wastewater. WP3 (Computational data analysis) and WP4 (Linking to epidemiology) advance modeling and statistical approaches to translate viral loads in wastewater to meaningful, policy-relevant indicators of disease trajectory that directly address the project Goals. Finally, WP5 (Capacity building and dissemination) collates and disseminates methods and findings to relevant stakeholders, with the goal of transitioning WBE from research to surveillance.",,2026,"Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich",2919393.96,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies,Disease transmission dynamics,2022 +P28605,196267,Real-time monitoring of COVID-19 transmission through phylodynamics,"I propose to analyse genomic sequencing and confirmed case data from the COVID-19 pandemic in order to quantify, in real-time, transmission dynamics as well as the total number of infections, including `hidden' infections from untested and asymptomatic individuals. The results will allow me to rapidly evaluate the effectiveness of public health responses, and to suggest changes to strategies if need be. I have three main objectives.My first objective is to quantify transmission rates and the effective reproductive number of COVID-19 across geographic regions in real-time. In particular, I will determine which public health interventions and which environmental factors such as population density, temperature, or humidity have an impact on the reproductive number within outbreaks. Second, I will quantify transmission between geographic regions, providing insight into the importance of cross-border transmission and the impact of closing borders on the pandemic. The third objective is to estimate the overall number of COVID-19 cases through time and across regions. These estimates are required to evaluate the number of people with immunity against Sars-CoV-2 and, in combination with the estimated reproductive number, to forecast future spread. Further, the estimates of the overall number of COVID-19 cases enable a refinement of estimates of the case fatality rate of the disease.I will employ phylodynamic tools which were developed in my group over the past years for doing this quantification. The quantification will be done on a country level, meaning information regarding transmission rates and effectiveness of public health interventions will be available on a country level. For Switzerland, I will focus both on the country-level as well as the Cantons of Basel-Stadt and Basel-Landschaft. The Basel results will in particular be directly communicated to the Vorstand Ärztegesellschaft Baselland, Ressortchef 'Public Health'.For Basel-Landschaft, as part of a different project, I am leading efforts to generate COVID-19 sequencing data. Further, my group is involved in curating and releasing the confirmed case data on a Cantonal level. All other data will be accessed through publicly available databases.",,2022,"Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich",303513.25,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +P28616,210070,The New Normal - How to Design and Implement New Work Arrangements That Are Fair and Satisfy Employees' Needs,"The Covid-19 pandemic has had a strong impact on how and where individuals work. For many organisations and employees, it seems out of the question to simply go back to the prepandemic workplace. As a result, organisations now face the challenge of implementing remote work arrangement policies that fit their business goals as well as their employees' needs. With the aim to help organisations to face this challenge, the current project will focus on the design and process of creating and implementing new work arrangement policies during and after the pandemic. More specifically, we aim to deepen our understanding of how (a) perceived fairness of the company's work arrangement policy as well as (b) the satisfaction of basic needs (competence, control, relatedness) by the policy are linked to employee work attitudes, performance, and well-being. Moreover, we aim to develop an intervention to support organisations as they design and implement new work arrangement policies. The project comprises four studies using different methodological approaches. Study #1 (the cross-sectional study) will provide representative data for Swiss working society concerning the prevalence of remote work, employees' needs, and their perception of the fairness of existing work arrangement policies. Study #2 (the longitudinal study) will test the prospective effects of remote work and the effects of perceived fairness and satisfaction of employee needs by work arrangement policies on our key outcomes, namely work attitude, performance, and well-being. Study #3 (the diary study) will offer detailed insights into where employees do their main tasks and where they would like to do them, where their basic needs are best satisfied, and whether employee performance and well-being differ depending on whether they work in the office or remotely. Building on the results of these three studies, we will develop an intervention. This intervention will include an e-learning tool, coaching sessions, and team workshops and will help in the design and implementation of work arrangement policies. The effectiveness of the intervention will be tested with Study #4, a longitudinal study with a control group (the quasi-experimental study). Our project will be supported by several implementation partners (business enterprises, a foundation, and a government agency). These partners will follow the project and serve as a sounding board to ensure that the studies and especially the intervention will fit practitioner needs and can be easily implemented in organisations. In sum, the current project aims to offer help for organizations that face the challenge to implement new work arrangement policies in the context of the pandemic. It aims to deepen our knowledge about antecedents and outcomes of employee perceptions of the fairness of remote work arrangements and about the satisfaction of employee needs under different arrangements. This knowledge will provide a basis for developing interventions to create and implement new work arrangement policies during and after the pandemic. For future pandemics, knowledge about employees' needs under remote work and about the role of fairness of policies will help organisations to implement work arrangements that promote employee well-being and performance. In line with the programme objective, the insights and intervention material from this project will help organisations to adapt to changing work conditions during and after a pandemic.",,2026,Institut Mensch in komplexen Systemen Hochschule für Angewandte Psychologie Fachhochschule Nordwestschweiz FHNW,531652.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2023 +P28630,213773,Microsecond Time-Resolved Cryo-Electron Microscopy,"Proteins are the machinery of life and are therefore inherently dynamic systems. Yet, much of what we know about proteins still derives from static structures, leaving our understanding of their function fundamentally incomplete. Observing proteins in action requires not only atomic spatial resolution, but also a temporal resolution that matches the fast motions of proteins, a challenge that has largely remained beyond the reach of existing methods in structural biology. As part of a previous ERC Starting Grant, our group has established a novel approach to cryo-electron microscopy (cryo-EM) that promises to enable atomic-resolution observations of the dynamics of proteins with microsecond time resolution. This is notably fast enough to capture the large-amplitude domain motions of proteins that are typically associated with their function and thus promises to fundamentally change what we can know about proteins. However, significant efforts remain to take our technique beyond the proof-of-principle stage and to develop microsecond time-resolved cryo-EM into a mature technique that will be broadly adopted. This is the goal of the present proposal. To this end, we will overcome a number of technical challenges that currently limit the scope of our method. In particular, the observation window will be extended to longer timescales, and a variant will be implemented that affords nanosecond time resolution. In order for our work to have impact, it will also be crucial to ensure that the technique can be easily adopted by other labs. We will therefore develop a simpler implementation that does not rely on the highly specialized equipment only available in our lab. Finally, we will demonstrate that microsecond time-resolved cryo-EM can be used to elucidate the dynamics of a broad range of systems that have previously been inaccessible. To this end, we will study the dynamics of protein folding, the gating mechanism of an ion channel, and the dynamics of the SARS-CoV-2 spike protein.",,2028,Laboratoire d'ingénierie moléculaire des nanomatériaux optoélectroniques EPFL - SB - ISIC - LIMNO,2419461.08,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P28637,196255,The language of the COVID-19 Pandemic: Investigating official communication and its relations with collective and individual emotions,"The coronavirus outbreak represents an unprecedented global health crisis as the pandemic continues spread, driving massive restrictions on fundamental, everyday-life behaviors (Paules, Marston, & Fauci, 2020). Individuals living in countries around the world have been instructed to profoundly alter their daily routines and behaviors, particularly those involving social contact. A global pandemic like the one we are currently experiencing constitutes not only a crisis of public health, but also major, collective, psychological upheaval that evokes strong emotional responses that require intra- and interpersonal regulation at both the individual and societal levels (Maercker & Horn, 2013). Past research has established that the manner in which disease and the health behavior regimens are communicated can either undermine or facilitate the success of public influence and its subsequent impact (Rubin, Potts, & Michie, 2010; Vaughan & Tinker, 2009). As such, the language itself that is deployed by official health channels plays a central role in modern public health systems, a point that has been increasingly acknowledged in recent years (Gostin, 2018). Moreover, in the current crisis, press conferences by non-medical experts, such as political leaders, have the potential for huge impacts on public health. For example, Chancellor Merkel`s speech on March 18, 2020 had around 25 Millions of viewers; the Swiss Bundesrat's and Boris Johnson's press conferences saw similarly high rates of viewership. Qualitatively speaking, it is evident that each individual government's leaders presented the same essential content - disease information, public advice, behavioral restrictions - in remarkably different ways. However, the complex interplay between each source's linguistic style and the social psychological landscape of each nation remains poorly understood. Our proposed research aims at not only understanding the linguistic fingerprint of these public communications and their differential impact on the general public, but the a priori public receptivity to each fingerprint.Collective emotional responses and coping strategies surrounding crises are directly reflected in everyday language used on social media, such as Twitter (Brummette & Fussell Sisco, 2015; Eriksson, 2016; Garcia & Rime, 2019). Likewise, individual reactions to collective experiences of crises are also reflected in daily language use (Mehl & Pennebaker, 2003). In the context of emerging technologies for the ""at scale"" automated psychological analysis of language data (Boyd, 2017; Boyd, Pasca, & Conroy-Beam, 2019; Boyd & Pennebaker, 2015b), this international study proposes to investigate both the language use in official webpages and statements during the COVID-19 crisis as well as collective and individual emotions and emotional regulation processes that publicly unfold through Twitter and more targeted, individual writings. Principally, we propose to accomplish through the analysis of language ""style"" rather than language ""content"". Importantly, the analysis of language style is a unique approach to psycholinguistic fingerprinting that can be parallelly studied across languages (Meier et al., 2019; Meier et al., 2020; Pennebaker, Boyd, Jordan, & Blackburn, 2015). Our central research questions are: Are there systematic differences between public communications in USA, UK, Germany and Switzerland? More specifically, are there societally impactful divergences in language styles (reflecting, e.g., analytical vs. narrative thinking (Jordan & Pennebaker, 2017; Pennebaker, Chung, Frazee, Lavergne, & Beaver, 2014) and references to the disease and virus (""Corona"", ""Chinese virus"", ""COVID-19"" etc.)? Are these differences related to collective emotional responses in Twitter over time and to intra- and interpersonal emotional regulation as measured in questionnaires and essays (Horn & Maercker, 2016; Horn, Samson, Debrot, & Perrez, 2019)? Additionally, we will explore how the language in official governmental communications are meaningful contributors to infection rates within their corresponding locales as the ultimate outcome of successful health communication during the crisis. Results of the study will inform further health communication and open the door for automatic tracking of collective emotional responses at scale during a public health crisis in order to allow timely public mental health interventions.",,2022,UFSP Dynamik Gesunden Alterns Universität Zürich,193104.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2020 +P28640,196140,"Impact of Sex and Gender on COVID-19 outcomes: Role of ACE-2, TMPRSS2, and gender-specific risk factors","Background: Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. Emerging evidence from China suggests that COVID-19 is deadlier for infected men than women, with a 2.8 percent fatality rate being reported in Chinese men versus 1.7 percent in women. Further, sex-disaggregated data for COVID-19 show a higher number of cases in men as compared to women. Mortality is highest in aged men and men with pre-existing cardiovascular disease. The mechanisms for the reduced reported cases and case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men.Aims and methods: We aim to analyse the available clinical and epidemiological data to confirm a reduced susceptibility of women towards COVID-19. We will clarify protective mechanisms in females by assessing clinical variables and verifying cellular and molecular key pathways in a murine model of sex hormone withdrawal, where tissue samples are already available. We hypothesize that sex related factors, such as sex hormone-driven innate and adaptive immune responses as well as hormone-regulated expression of genes encoding for the SARS-CoV2 entry receptors angiotensin converting enzyme (ACE)-2 receptor and the cellular serine protease TMPRSS2 are involved. Furthermore, gender-specific lifestyle behaviour such as smoking, psychological stress, and socioeconomic conditions will be included. Specific demographic groups including male patients on anti-androgenic treatment for prostate cancer or women receiving hormone treatment will be assessed in a prospective observational cohort study performed at the University Hospitals Zurich, Basel, and Bern. We expect that the risk of disease transmission and manifestation varies depending on sex hormone status. Further, the influence of female and male sex hormones, postmenopausal hormone replacement therapy (HRT), number of pregnancies and hormonal contraception on COVID-19 disease severity and outcome will be assessed. The acquisition of blood samples from severely ill patients hospitalized for COVID-19 will allow analysis of inflammatory profiles and their interaction with sex- and gender-specific variables. Finally, existing tissue samples from gonadectomized or sham operated young, middle aged and senescent mice of both sexes will provide information on whether the expression of ACE2 and TMPRSS2 in heart and lungs depends on age, sex, hormonal status and their interaction. Relevance and Impact: Gender disparities observed in COVID-19 vulnerability clearly emphasize the need to understand the impact of sex and gender on incidence and case fatality of the disease so that timely treatment in highly vulnerable demographic groups can be tailored to their specific needs. The proposed project will combine clinical data from ongoing cohort studies with experimental work in mice. This strategy allows rapid analysis of data and implementation of results. Our work will identify both, sex- and gender-related predictors of severe variants of COVID-19 and has the potential to identify effective therapeutic interventions.",,2021,Klinik für Nuklearmedizin Departement Medizinische Radiologie Universitätsspital Zürich,270532.01,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Gender,,,Switzerland,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Prognostic factors for disease severity | Disease pathogenesis,2020 +P28645,196736,Developing standards for institutional health communication during public health emergencies. Learning from information around COVID-19 pandemic as a case in point.,"BackgroundBy focusing on the recent outbreak of the coronavirus disease of 2019 (COVID-19) pandemic, the proposed project studies official/institutional health communication from authorities to the public during public health emergencies. This communication involves the presentation of risks under uncertainty. Risk communication is an established field. Yet, there is a gap in the literature on how to strengthen official communication in contexts of information overload and misinformation. As Dr. Teohos Adhanon Ghebreyesus, WHO's director general, declared at the media briefing on COVID-19 on March 5th, 2020, ""The fight against rumors and misinformation is a vital part of the battle against this virus"". The problem of misinformation and information overload is currently highlighted in Switzerland. Main open research questions include: What are the main challenges that institutions face in communicating in such an overload of information? How can they provide guidance and combat misinformation? How can they communicate in a way that influence people's risk perception and behavior towards evidence-based recommendations for prevention?ObjectiveThe overall objective is to develop standards for institutional communication of health information during public health emergencies, with a focus on how to guide people's risk perception and behavior and to combat misinformation.Methodological approach. This project will adopt a mixed-method approach. It will be subdivided in an analytical phase and a normative phase. The anlytical phase will be devoted to the description of institutional health communication around the COVID-19 outbreak, what and how it has been communicated by institutions, how it was reported by the news media and received by the public. Here, a content-analysis, semi-structured interviews and a population survey are planned. The normative phase will entail the creation of a toolkit composed of a theoretical framework and operational guidelines on how to best deliver health information during public health emergencies and in contexts characterized by misinformation. The toolkit will be validated through a Delphi study with stakeholders.Expected resultsThe proposed project will result in extensive and through understanding of institutional communication and, specifically, of the difficulties that can hinder persuasiveness of the health messages, and of what aspects have to be strengthen to solve them. It will develop concrete communication strategies that are evidence-based and grounded in the experience of stakeholders and the perceptions of the population in Switzerland during COVID-19 pandemic. Specifically, the strategies will address the sender (i.e., how institutions can disseminate information in a way people trust and perceive as relevant and important), the message (i.e., what messages can look like according to elements that include the uncertainty of information and their framing, tone, and linguistic characteristics), the receiver (i.e., how communication can influence people's perception and behavior), the channels, (i.e., how messages can be adapted to engage people using different communication), and the context (i.e., how to address parallel information from other sources and misinformation).ImpactThe proposed project is expected to have an important rapid translation outcomes as the planned toolkit will give concrete strategies for ad hoc institutional communication for the Swiss context, developed with the input of relevant stakeholders and soundly based on the analysis of institutional communication in Switzerland during COVID-19 and through a process of consensus. In parallel to this, the proposed project is expected to be of high scientific importance, as research about health risk communication in contexts of high information flows is in its infancy. Results from this project will contribute to advancing the field by providing insight on problems faced by institutions in the design and delivery of health information during public health emergencies by identifying and providing strategies to influence individuals' perceptions and behaviors, focusing on how to combat misinformation.",,2023,University of Lucerne,300744.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P28646,203488,Rational design of neutralising antibodies resilient to virus escape,"The current outbreak of a previously unknown betacoronavirus, SARS-CoV-2, started in 2019 in the city of Wuhan, China. Within a few weeks it reached pandemic proportions. As of today, virtually every country was involved and the virus caused over 160 million infections, claiming millions of lives. SARS-CoV-2 is the third coronavirus to cause outbreaks in less than twenty years. However, unlike the previous two, SARS-CoV-2 will likely continue to circulate and cause disease. Thus, there is urgent need to discover and develop effective preventive measures and treatments. Passive immunotherapy with recombinant monoclonal antibodies (mABs) that bind to the SARS-CoV-2 spike (S) protein on the virus surface, has proven highly effective in preventing progression to severe disease if administered early to individuals with COVID-19. In fact, a single injection of mABs provides immediate protection, making mABs an ideal complement to vaccination in high-risk populations and individuals that fail to respond, or respond only poorly to vaccines. The early success of first-generation mABs against SARS-CoV-2 has prompted regulatory agencies to provide emergency use authorization (EUA). However, the emergence of SARS-CoV-2 variants, that bear amino acid changes in the S, threatens to reduce the effectiveness of these first-generation mABs. Therefore, innovative strategies are needed to anticipate the dangers posed by new SARS-CoV-2 variants, which are expected to emerge. The overall goal of this proposal is to design, produce and evaluate a novel kind of antibody, an antibody that is resilient to virus escape, and to rapidly develop it towards clinical testing in patients infected by SARS-CoV-2. The entry of SARS-CoV-2 into human cells depends on the receptor binding domain (RBD) of the virus S protein engaging its primary cellular receptor, human angiotensin-converting enzyme 2 (ACE2). Consequently, antibodies that bind to the RBD are able to potently prevent infection and disease. The RBD is however also one of the most mutable regions of S, and several virus variants of concern (VoC) with amino-acids substitutions in the RBD have emerged. Importantly, these substitutions, while reducing the affinity of existing antibodies to S, do not reduce, and in many cases increase, the affinity of the virus for its receptor. Taking advantage of this fact, we will design and evaluate new molecules that combine the soluble portion of ACE2 with carefully selected human mABs, generating chimeric AntiBodies REsiLIEnt to Virus Escape (AB-RELIEVEs). These antibodies will have the advantage that escape mutations reducing the affinity of the AB-RELIEVEs will also decrease the affinity of the virus for its receptor, thus reducing its fitness. Conversely, mutations increasing the affinity to ACE2 will automatically improve AB-RELIEVEs' binding.To achieve this goal, we will:(1) use computer modelling to design chimeric antibodies (AB-RELIEVEs) starting from available atomistic structures of complexes of ACE2, S protein and various antibodies; and (2) perform isolation of novel antibodies binding to specific portions of the S protein, at optimal distances from the ACE2 binding domain on the RBD; (3) recombinantly produce, biochemically characterize and evaluate AB-RELIEVE for neutralization of SARS-CoV-2 in vitro and in vivo.",,2023,Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice,447779.36,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P28648,205600,[BC]2 Basel Computational Biology Conference 2021,"The [BC]2 Basel Computational Biology Conference is Switzerland's main event in the domain of Computational Biology and one of the major events of its kind in Europe. Organised by the SIB Swiss Institute of Bioinformatics, the conference will take place 13 - 15 September 2021 and is entitled ""Harnessing biological data: from molecular processes to human health"". [BC]2 will be organised as on-site event combined with virtual participation options. The conference expects approx. 400-500 participants. In case national or local COVID-19 measures prohibit large events, [BC]2 will be organised as virtual event.The conference will feature some of the latest developments in cancer and precision medicine, clinical population genomics, infectious diseases, single-cell biology, evolutionary biology and ecology. It combines inspiring keynote lectures by international experts with presentations of the latest scientific results and methods in the field, workshops and tutorials fostering hands-on capabilities, and poster sessions along with social and networking activities.",,2021,Biozentrum der Universität Basel Systembiologie,27322.78,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2021 +P28652,221283,Long-term Mortality Effects of In-Utero Exposure - The 1918/19 Pandemic as a Natural Experiment with Relevance for the Future?,"Infectious diseases and especially pandemics can have long-term health effects in addition to the immediate ones. This also applies to the intra-uterine environment, as the so-called Barker hypothesis states. Prospectively, one can only speculate whether the COVID-19 pandemic will have an impact on the current birth cohorts in the coming decades. A look back into the past could serve as a warning as it has been shown that the birth cohort of 1918/19 (in utero during the 'Spanish flu' and during the end of World War 1) had a reduced life expectancy from the age of 50 than the birth cohorts before and after. However, what has not yet been investigated are the specific causes of death leading to a higher mortality risk of the 1918/19 birth cohort later in life. So far, it is not known what the exact reasons for the increased mortality risk are and what causes of death lead to it, and if the causes of death depend on trimester in which the in-utero exposure took place. Furthermore, it is not known yet, if the causes of death depend on birth place, which can be attributed to the severity of the ""Spanish flu"" in the respective place. The latter is particularly important for Switzerland, a multilingual country with cultural diversity, which also has regional differences in pandemic policy and mortality.Therefore, the first objective of this study is to identify the main causes of death for the 1918/19 birth cohort in Switzerland and to compare the risk of dying from these causes with that of the surrounding birth cohort. The annual changes of the main causes of death are shown visually via a Lexis surface plot and modelled with an adapted hierarchical age-period-cohort model. The second object is to investigate whether the causes of death depend on the trimester in which the in-utero exposure took place, which is analysed with Fine and Gray competing risk regression models estimating hazard ratios of the cause-specific mortality. Third, the study identifies the spatial pattern of cause-specific mortality in later life of the birth place for those born in 1918/19 and relates it to the spatial pattern of the severity of ""Spanish flu"" (estimated by excess mortality, influenza morbidity or mortality) in each district using Bayesian diseased mapping models and spatial fusion models.Studying this is important to better understand how much exposure to an infectious disease during pregnancy affects life expectancy and how the risk of certain causes of death is affected by the severity of exposure. Since Switzerland was affected differently by the ""Spanish flu"" (due to geographical, demographic and cultural differences), spatial data help to analyse differences in cause-specific mortality due to different levels of exposure across the districts and due to exposure in different trimesters. In order to determine the main causes of death in those born in 1918/19, individual anonymised death data from 1969 - 2021 for cause-specific deaths are made available by legal agreements with the Swiss Federal Statistical Office. The weekly number of ""Spanish flu"" morbidity and mortality of each district will be transcribed and digitized to a database from the ""Bulletin of the Swiss Health Office"" for the years 1918/19.This study will result in a deeper understanding on long-term effects of an in-utero exposure to an infectious disease and assist in deriving appropriate interventions. Post-pandemic surveillance of a pandemic on neonatal health should be an important component of public health policy, in the post-COVID-19 era and also in future pandemics. Effects of in-utero exposure to COVID-19 of the current birth cohorts later in adulthood cannot yet be studied. However, the impact of past pandemics on in-utero exposed birth cohorts can be studied to raise awareness among today's health policies.",,2025,Anthropometrics & Historical Epidemiology Institute of Evolutionary Medicine University of Zürich,112718.94,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2024 +P28661,198908,Annual meeting of the Swiss Society for Neuroscience,"The central aim of the Swiss Society for Neuroscience (SSN) meeting is to bring scientists from Switzerland at all career levels together to share and discuss their latest research findings, to learn about new technological or key conceptual developments in neuroscience, to network and to explore new collaborations. Next year's meeting is scheduled to take place on Saturday, January 29 & 30 2021 at the University of Fribourg. Despite the great challenges imposed by Covid-19, more than 400 researchers and clinicians from Switzerland are expected to attend this meeting, which is the major Swiss venue for exchange of current scientific information in the area of brain research. The meeting has a wide focus that includes molecular and systems neuroscience, as well as clinical research and neural computation / bioinformatics. The meeting will take place in our modern lecture halls of the University of Fribourg with extra-space between participants and for the first time also with an online viewing possibility to face the current Covid-19 situation.The local organizing committee is pleased to present a very exciting scientific program, including presentations by world-renowned experts and four parallel symposium oral sessions. The keynote lecturer Prof. Gilles Laurent from the Max Planck Institute for Brain Research in Germany, a world-wide leader in Neuroscience who will speak about his institute's efforts to delineate cortical circuit computations in vision and olfaction. There will also be a large poster session in person and online, fostering interaction and exchange of scientific ideas among the participants. A special aspect of this year is a presentation of the new movie documentary by Jean-Stéphane Bron about the brain followed by a discussion with Monsieur Bron, neuroscientists and teachers about education, didactic methods and knowledge acquisition.The meeting is attended by many young scientists including doctoral students and postdocs, and indeed these young members of the SSN are organizing one of the parallel symposia in 2021, as well as a career workshop.We anticipate that the event will have a very positive impact on the ongoing development of neuroscience in Switzerland, including the generation of fresh ideas for new projects and methods developments to study the brain. Capitalising on the public event with Swiss film maker Jean-Stéphane Bron and his latest documentary on the brain, we believe the event will help to strengthen the general public's awareness for the brain and neuroscientific research.",,2022,Département de Médicine Université de Fribourg,4215.48,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2021 +P28662,211082,Mechanisms and evolution of innate immune signalling activation across species,"Only certain species act as pathogen vectors or reservoirs for diseases such as COVID-19, malaria, or tuberculosis. Variability in disease outcome is partly driven by differential activation of the immune system after otherwise identical infections, particularly true for inflammatory diseases such as Influenza and COVID-19. The inflammatory response is driven first by activation of innate immunity: an evolutionarily conserved defence system built upon recognition, signalling, and effector molecules. Genes involved in the innate immune response are some of the most rapidly evolving in the genome. Previous analyses have highlighted recognition and signalling proteins in particular as having very high rates of adaptive evolution. However, few studies have examined innate immune induction across related species, and little effort has been made to understand how molecular evolution in conserved immune pathway genes might drive differences in immune induction across species. My research has shown related fly species given identical infections can differ markedly in their induced immune response. Here, I will take a comparative approach to systematically characterize immune induction patterns in diverse species. Differences in immune induction should rely on either i) alternate immune signalling epistasis/cross-talk, or ii) specificity encoded via gene duplication, allowing evolution of novel pathway connections. I will assess gene expression, copy number variation, sequence evolution, and signalling epistasis, to understand how these variables produce differences in immune activation. I will then tie immune evolution to differences in the induced response to infection. This will reveal the mechanisms underlying differences in immune activation across species. Major global threats such as COVID-19, malaria, or tuberculosis, each induce common immune pathways shared by all animals. This proposal will therefore greatly improve our ability to predict interactions between novel hosts and pathogens, and understand innate immune factors affecting disease severity.",,2024,Disease Ecology and Evolution University of Exeter,110670.31,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P28666,205306,The Future of Work,"The volume 'The Future of Work' is a collective, interdisciplinary effort to grasp the trends that were reshaping the world of work before the Covid-19 pandemic along with the effects of the pandemic on workers and labor markets. Written in the immediate aftermath of the outbreak, as countries around the world grappled with the economic fallout, the volume's 12 contributions from leading researchers and junior scholars draw on the rich debates of the 2019 Congress of the Swiss Sociological Association on the Future of Work held at the University of Neuchatel in the fall of 2019. The chapters, divided into five sections, cover issues ranging from the (sometimes unexpected) impacts of digital technologies and globalization to the experience of marginalized workers and the future of academia. Their critical insights into the historical dynamics and lived experiences behind the transformation of work provide a framework to understand the fate of workers and occupations in these unsettling times.",,2021,Institut de sociologie Université de Neuchâtel,17622.33,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts | Other secondary impacts,2021 +P28675,204363,Synthetic single domain antibodies to understand and fight morbilliviral infections,"Background. Several RNA viruses, belonging to the family Paramyxoviridae, continue to pose threat to hundreds of thousands of human and animal lives each year. Measles virus (MeV), canine distemper virus (CDV) and Nipah virus are among the paramyxoviruses that are of high clinical relevance, and this despite the fact that very efficient vaccines are available against MeV and CDV. No specific treatment option is available to address the global burden these viruses bring each year. Several approaches have been tried simultaneously to discover antivirals against each of these RNA viruses. However, monotherapy approaches inevitably pose the challenge of the rapid emergence of escape variants against the identified antiviral. Specific aims. To potentially tackle this hurdle, this project proposal aims at discovering broadly neutralizing multidomain synthetic single domain antibodies (sybodies) to fight morbilliviruses. To achieve this ambitious goal, a two-pronged strategy will be conducted:1.Identify, characterize and format broadly neutralizing sybodies against morbilliviruses.2.Identify, characterize and format sybodies against host protein(s) promoting morbilliviral infections.Experimental design. To successfully achieve Aim 1, state-of-the-art molecular, cellular, biochemical, functional and virological technologies, that are available in my laboratory, will be combined with a tuned selection procedure associated with a unique synthetic nanobody (sybody) platform (Laboratory of Prof. Seeger, University of Zurich, Switzerland). The strategy is designed to increase the chances to discover broadly neutralizing anti-morbilliviral binders. Upon molecular characterization of their mode of inhibition, best sybody candidates will be fused together to engineer multidomain antibodies. Aim 2 will focus on the detailed molecular characterization of 'top-ranked' host factor candidates that may be essential in promoting morbillivirus infections, which were identified in a recently conducted genome-wide CRISPR/Cas9 functional screen. Later on, the discovery of sybodies blocking the identified host factor's function will be undertaken. Furthermore, best broadly neutralizing binders will be next investigated in primary cell systems against multiple strains of CDV and MeV as well as tested in well-established in vivo models of morbillivirus-induced pathogenesis. Strikingly, both aims have the great potential to discover antivirals with (i) broad-spectrum efficacy and (ii) the opportunity to mitigate the generation of drug-escape variants.Significance. Despite available vaccines, MeV and CDV still cause significant health impacts. On the other hand, both attenuated strains hold great promise as vectors against cancers. Although very attractive in supporting both indications, no FDA-approved antivirals are available against both morbilliviruses. This proposal thus aims at discovering and rationally formatting, next-generation, broadly neutralizing, multidomain antibodies to fight those viral diseases. Key advantages of the project are: (i) the direct access to an innovative platform allowing robust and fast generation of highly potent sybodies against the morbillivirus H protein, (ii) the availability of biochemically and functionally well-characterized various H constructs, (iii) the already performed CRISPR/Cas9-based genome-wide functional screen, (iv) the long-held expertise in virology in my laboratory combined with all necessary collaborators to successfully reach the goals of this project proposal, and (v) the possibility to translate the strategy of selection of broadly neutralizing sybodies to other important viruses in a near future. In summary, rationally engineered neutralizing multidomain antibodies may not only represent a highly needed line of defense against morbilliviral epidemics, but may also improve the biosafety levels of the associated virotherapy platforms.",,2026,Abteilung für Klinische Forschung Dept. für klinische Veterinärmedizin Universität Bern,773284.57,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",,2022 +P28676,198314,Neutralizing multivalent antibodies against coronaviruses,"The COVID-19 pandemic, induced by the emergent SARS coronavirus (CoV)-2 (SARS-CoV-2), creates a global health emergency. The SARS-CoV-2 cell-entry process is mediated by the trimeric Spike (S) glycoprotein, which also represents a major viral antigen naturally targeted by the immune system. In this proposal, we propose to develop neutralizing multivalent single-chain antibodies (nmAb) to efficiently block viral cell-entry. The initial asymptomatic phase induced by the virus may offer a window of opportunity to establish post-exposure prophylaxis and prevention of human-to-human transmissions. Engineering of nmAbs will be performed in two main steps: (i) selection of neutralizing synthetic single-domain antibodies (sybodies) targeting various functional domains of S-trimers, and (ii) linking of sybodies together with or without grafting to a human immunoglobulin Fc-region. As sybodies are generated entirely in vitro, we can precisely steer the binder selection process towards targeting three, non-overlapping epitopes: i) Sybody 1 blocks ACE2-interaction via the RBD. We have already generated such sybodies [34]; ii) using the prefusion-stabilized and postfusion SARS-CoV-2 soluble S-protein, we will identify sybody 2 that stabilizes the prefusion-state and thereby prevent conformational changes required to complete the viral entry process; iii) using prefusion-stabilized soluble S-protein of SARS-CoV-2, SARS-CoV-1 and MERS, we will generate sybody 3 addressing highly conserved epitope among sarbecoviruses and even among ß-coronaviruses (Seeger lab). Membrane fusion- and cell entry-inhibition by the sybodies and derived antibody-like formats will be initially investigated in cell-based fusion assays as well as neutralization assays using pseudo-typed VSVs (Plattet lab), and later on against recombinant-live viruses. Finally, epitope mapping of best neutralizing sybody candidates will be tackled by cryo-electron microscopy (cryo-EM) and single particle 3D-reconstruction (Fotiadis lab). This will enable for the rationale selection of attractive sybody combinations for our nmAb engineering approach (Plattet lab). We envisage developing nmAbs towards two different formulations: (i) three fused sybodies (triSy), devoid of an added Fc-region, for nebulization (inhaled mainly as prophylaxis); and (ii) nmAbs grafted onto engineered human Fc-region for injection as either a preventive measure or treatment of further-progressed disease. In our judgement, nmAbs exhibit the following clinical advantages. Firstly, they may outcompete conventional antibody potency, because they bind to multiple epitopes of the Spike simultaneously. Secondly, multivalent binding of nmAbs may mitigate the rapid emergence of drug-resistant viral variants. Thirdly, treatment with nmAbs may reduce antibody-dependent enhanced (ADE) illness, since Fc-mediated effector functions can be rationally attenuated. In conclusion, we are confident that the design of next-generation neutralizing multivalent single-chain antibodies may represent an essential first line of defense against this and future emerging coronavirus epidemics.",,2022,Abteilung für Klinische Forschung Dept. für klinische Veterinärmedizin Universität Bern,860267.53,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P28680,214512,Imagined Immunities: A History of Our Collective Resistance to Disease,"During the COVID-19 pandemic no scientific concept has been more contested in the Anglophone world than ""herd immunity."" While some scientists considered herd immunity to be the inevitable endpoint of the pandemic, with or without a vaccine, others believed it should have a more restricted meaning as an elimination threshold attained exclusively through mass vaccination. Was herd immunity something that would happen after most of us were infected, or did it mean that most of us would never become infected? Does herd immunity denote the widespread immunity acquired from infection that pushes a virus to become endemic, or is it the opposite: the elimination of a pathogen from a population via mass vaccination?This project seeks to clarify this scientific dispute by understanding the historical origins and development of the idea that populations can become ""immune,"" a term ordinarily reserved for individuals. Imagined Immunities: A History of Our Collective Resistance to Disease proposes that the origins of today's disputes reside in the deep history of a term which has developed a conflicting set of scientific uses and meanings over the course of a century. Analyzing the history of scientific efforts to envision human communities as immune and, ultimately, to make them so, Imagined Immunities will make unique contributions to the history of science and medicine while also advancing contemporary scientific and public health discussions.",,2025,"Centre for the History of Science, Medicine and Technology Oxford University",174571.69,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United Kingdom,,,,2023 +P28683,200917,The transmission of macroeconomic shocks and the housing market,"Housing services are not only an important consumption good. The housing asset and the corresponding mortgage liability are the dominant items in the balance sheet of most homeowners. The great recession and the ensuing financial and economic crises in the US and Europe have demonstrated that the transmission of macroeconomic shocks to the economy is shaped by the housing and mortgage market. Understanding the details of how this market affects the transmission is particularly important in low-interest rate environments with inflated house prices that pose risks for economic and financial stability. The proposed project consists of three subprojects that will be part of dissertations. Each subproject tackles the research topic from a different angle, providing new insights on (i) how monetary policy shocks transmit to the housing market, (ii) how fiscal tax incentives affect the macroeconomic consequences of house price corrections, and (iii) how the Covid-19 macroeconomic shock passes through to rents and house prices depending on the local industry and employment structure.",,2023,Schweizerisches Institut für Empirische Wirtschaftsforschung (SEW-HSG) Universität St. Gallen,463903.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P28704,209859,Family Violence and COVID-19: The Pandemic Within the Pandemic,"Early in the pandemic, various parties expressed fear of an increase in family violence (FV)-especially against women and children-due to COVID-19 containment measures that intensified known risk factors for FV (e.g. social isolation, women being pushed back into traditional gender roles) while reducing options for support. In many countries like Italy, France or Australia, this fear came true. However, whether or not the pandemic had an impact on FV in Switzerland is still a matter of debate. Nothing is known about possible long-term effects. Adopting an intersectional and intergenerational approach to FV, the proposed research project will study short-, medium- and long-terms effects of the COVID-19 pandemic on FV and develop recommendations for violence prevention measures in times of pandemic that go beyond the individual level and consider the interaction of structural and interpersonal violence.The project has three objectives: (1) monitor and document the development of FV during the pandemic; (2) analyse the impact of pandemic-related public health measures on the dynamics of FV and victims' help-seeking. With this, we aim to learn more about the dynamics of different types of FV (e.g. child maltreatment, intimate partner violence) during different phases of the pandemic for various groups to better understand the complex interplay of proximate and distal risk and protective factors that make some families more vulnerable to violence and others more resilient. Further, we will identify perceived barriers to and facilitators of victims' help-seeking during the pandemic and (3) develop evidence-based pandemic-specific recommendations for primary, secondary and tertiary FV prevention with different stakeholders to strengthen families and better protect victims of FV in times of pandemic. The project thus focusses on supporting both individual welfare and collective welfare, as FV also affects society as a whole (e.g. through health costs, productivity loss).To achieve the project's three objectives, we combine qualitative and quantitative methods, taking perspectives from different stakeholders into account: (1) To monitor the development of FV, we will gather and analyse multisectoral administrative data (e.g. police crime statistics) and self-report survey data on FV prevalence in pre-pandemic, pandemic and post-pandemic years. (2) To understand the dynamics of and typological differences in FV, we will conduct narrative interviews with members of families in different language regions of Switzerland exhibiting different risk and protective factors for FV (n = approx. 48) to reconstruct various conflict and violence dynamics. We will identify facilitating factors and barriers to victims' help-seeking and survey victims' assessment of the suitability and accessibility of different prevention measures. Further, selected results of the interview study will be tested via the self-report panel survey used to estimate FV prevalence (see above). (3) Based on these results, pandemic-specific recommendations regarding violence prevention measures will be developed in three steps: First, we will conduct a review of scientific literature and practice-based reports on suitability and accessibility of traditional and more innovative FV prevention measures during the pandemic. Second, we will conduct six focus groups with experts in different fields and language regions to learn about their experiences with violence prevention during the pandemic. Third, we will survey a larger sample of experts in various relevant fields and all language regions (n = approx. 400) to assess the recommendations derived from the analyses.The findings will enable federal and cantonal policymakers in different sectors to consider a possible increase in FV and its consequences for different population groups when implementing different containment measures and when developing strategies for violence prevention during the pandemic or when allocating funds to support families and victims of FV. Further, the findings can be used to develop strategies to increase family resilience and thus buffer negative (long-term) effects of the current and future pandemics. In addition, the findings will aid professionals working in related authorities, organisations and services in supporting victims in times of pandemic. The findings will also aid estimation of possible long-term effects of the COVID-19 pandemic on FV and subsequent additional support needs of different population groups.",,2026,Institut Sozialarbeit und Recht Hochschule Luzern - Soziale Arbeit,467007.55,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Social impacts | Other secondary impacts,2023 +P28721,203170,"Inpatient health care utilization before, during and after the coronavirus pandemic: Long-term trends, short-term changes, and their drivers","Updated project title: Routinely collected health care data to monitor and evaluate effects of health services: Impact of telemedicine on nursing home residentsBackground and rationale: Telemedicine (i.e., remote audio or video consultations with a clinician at real time) has the potential to improve access to health care. It has a particularly high potential to improve the quality of health care services provided in nursing homes. Residents often have mobility restrictions, making it difficult to travel for in person visits, and rely on emergency services instead. Telemedicine use quickly expanded at the start of COVID-19 pandemic in 2020 in many countries, but it is not well known whether it remained widely used afterwards and how it changed overall patterns of nursing home residents' health care.Objectives and aims: This project studied the effects of telemedicine adoption for routine and specialist consultations in US nursing homes in 2020-2022. The project first aimed to describe the overall specialty care use in nursing home residents, and how it changes for patients moving in from previous independent or community living setting. Next, it aimed to describe the adoption of telemedicine in nursing homes and study its effect on access to health care. Finally, it identified further health care policy changes in US nursing homes in 2020-2022 and explored how they changed residents' care.Methods: I used Medicare health care claims (covering up to 50 million elderly and disabled US patients annually) and Minimum Data Set (regular survey on US nursing home residents) data to identify nursing home residents and health care services they received in 2017-2022. The three studies used descriptive statistics to count the number of total and telemedicine visits, identified by service- and place-specific codes, over time. I applied logistic regression models to identify resident, nursing home, and provider-specific characteristics of telemedicine use. Finally, I applied difference-in-differences analysis to compare health care received in high- vs low-telemedicine adopting nursing homes in clinical scenarios that often result in barriers to care in nursing homes. Results:Telemedicine was rapidly adopted for nursing home residents' care in the US in early 2020, increasing from 0.15% of all visits in February 2020 to 15-25% of visits in May 2020. Subsequently, it stabilized at a low use rate (2-8% depending on the visit type) Higher telemedicine use was associated with improved access to psychiatry visits in the nursing home, but had a smaller impact in other clinical scenarios, such as visits for residents with limited mobility or new specialist visits. Overall, the use of specialty care falls significantly after patients transition to a nursing home in the US. Among long-term care residents with previous specialty care use, the proportion of residents with visits decreased consistently in all specialties in the 12 months after the transition, ranging from a relative decrease of 14.4% for orthopedics to 67.9% for psychiatry visits. The decrease was similarly high even among residents with a diagnosis likely requiring continued specialty care. Telemedicine use in nursing homes in the US was enabled by a waiver allowing its reimbursement for Medicare beneficiaries at parity with in-person visits. Another public health emergency waiver removed the requirement that nursing home residents can receive reimbursed skilled nursing care only after a 3-day hospitalization. This project found that the introduction of this waiver increased the number of such nursing care episodes markedly, particularly in the first year of the COVID-19 pandemic. The waiver was used primarily among certain types of facilities and for long-term care residents with COVID-19, and it did not result in overall substantially higher skilled nursing care costs - all suggesting its successful implementation.Conclusions and impact:While adoption of telemedicine and relaxation of other rules on reimbursement rules in nursing homes helped to provide valuable health care services to residents during peak COVID-19 pandemic times, they did not have a lasting impact on the overall patterns of care use. The majority of nursing homes reverted to low telemedicine use, although higher than before the pandemic, from 2021. More sustained effort and further incentives will be needed for residents to benefit fully from the flexibility and increased access that telemedicine can provide in nursing homes.",,2023,Dept. of Health Care Policy Harvard Medical School,139386.58,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Digital Health,,,United States of America,,Health Systems Research,Health service delivery | Health financing,2021 +P28723,210965,Passport power: the value and semiotics of citizenship in a post-pandemic world,"Citizenship is a status granted to almost all human beings at birth. It is a fixture of contemporary international order, central to global governance, trade, diplomacy, and Western ideals of liberal democracy. However, citizenship is not a natural status with inherent, everlasting value. Rather, it is an extremely dynamic social institution that incorporates notions of inclusion/exclusion, rights, everyday conduct, acts of deliberation and debate, policy and political participation, and global mobility, all at once. Critical scholars argue that citizenship works much like the air we breathe: all around us, but largely unnoticed (Spiro 2020). In this respect, it operates much like discourse - language and other semiotic resources in use - in that its nature is broadly unquestioned in citizens' everyday lives. In very basic terms, most citizens of Western countries take their citizenship for granted. However, citizenship is also highly valuable. It means a lot and is worth a great deal to both the states which grant it, and the individuals who have it granted on them (or 'earn' it, often through great sacrifice). Given this value, how is citizenship sold, marketed, branded and appreciated in modern everyday life? How do these discursive, evaluative, and economic processes intersect with globalised forms of social inequality and immobility? This project's core aim is to complicate common understandings of the meaning and purpose of citizenship, and to explore (and expose) citizenship for what it is: ultimately, a resource for regulating and exploiting modern-day privileges of global mobility.The proposed project employs sociolinguistic (critical discourse analysis, narrative analysis) and visual/social-semiotic methods to examine dominant representations and ideologies circulating around this oft-cited yet often taken-for-granted concept. It will enrich understanding of the discursive foundations of citizenship against backdrops of late capitalism, unequal global mobility, consumer culture, and neoliberalism. In sum, I will analyse citizenship from a broad-based, global perspective, recognising that the social, political, and economic value of citizenship (the concept) and particular citizenships (e.g. Australian, Swiss, Irish) is effectively a rhetorical construct. It is a product sustained through interpersonal conversation, material, performative texts (e.g. passports), ceremonial practices, branding, institutional media and marketing, digital discourse, and banal, everyday communication. Until now, these textual and discursive underpinnings for citizenship - the mediation of this institution through language and other forms of meaning-making - has gone somewhat overlooked.Overall, the proposed project will bridge the gap between scholarship describing transformations of citizenship in the current day, and scholarship investigating the sociolinguistics of global mobility and the political economy of language. To do so, I examine 4 'articulations' of the value of citizenship (i.e. 'sites' of citizenship discourse, where citizenship is marketed, appraised, and evaluated): citizenship-by-investment (CBI), passport design, citizenship ceremonies, and social media support groups during COVID-19. Studying these articulations allow me to explore 3 theoretical, critical, and applied objectives:-to describe how citizenship is established in discursive and semiotic practices as a valued/valuable commodity;-to link dominant discourses of citizenship in the current day to historical relations of power, the market, migration, colonial exploitation, and prejudice; and-to raise awareness about the (discursively-enacted) commodification of citizenship, in order to redress the inequalities and injustices implicated in this process.Informed by critical studies of the sociolinguistics of global mobility, forms of linguistic commodification (Heller 2010) and the centrality of language to marketing practices (Kelly-Holmes 2019), the proposed project thus contributes analysis of the commodification and marketisation of citizenship to scholarship investigating the contemporary political economy of language (e.g. Martín-Rojo and Del Percio 2019). The productive framework I will develop for understanding the semiotics of citizenship is a vital undertaking in an era of uneven mobility, climate emergency, and stark social inequality, with institutions strained by the pandemic and refugee flows. The project's scholarly outputs include a submitted book proposal (monograph), and progressive findings will be disseminated through four publications (D1-D4 in the included schedule) and four oral presentations at high-level conferences in the fields of sociolinguistics, linguistic anthropology, and discourse studies.",,2025,Modern Languages and Applied Linguistics University of Limerick,140133.42,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Ireland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P28727,212380,Proteolytic targets in cell death and inflammation,"Granule serine proteases and cysteine cathepsins of immune cells regulate physiological and pathological processes through the cleavage of substrate proteins. These highly reactive enzymes are stored in specialized lysosomes and are released into other cellular and extracellular compartments to perform their homeostatic and antimicrobial functions. Proteases are also accidentally released into the cytosol after granule leakage or extracellularly after cell death causing cellular and tissue damage. Serpins are the largest family of serine and cysteine protease inhibitors and are essential for the regulation of proteolysis in humans as shown by inborn diseases caused by inherited serpin gene defects. In vertebrate evolution, serpin genes were duplicated, providing redundancy and opportunity for the evolution of new regulatory functions to control proteolysis and maintain homeostasis and immunity. We have previously identified essential functions of clade B serpins in the inhibition of leukocyte serine proteases in cell death, inflammation, and infection. In particular, we have shown the importance of certain protease-serpin axes in a cell-specific manner. We have also found that serpin deficiencies are associated with higher release of cytokines and delayed resolution of inflammation and infection. Particularly, we have shown that the neutrophil serine protease cathepsin G preferentially activates gasdermin D leading to enhanced release of pro-inflammatory IL-1ß in absence of cytosolic serpins. However, molecular mechanisms leading to cathepsin G-mediated cell death and to release of other cytokines by uncontrolled proteases remain to be discovered. Using an unbiased proteomic screen, we have now identified novel target proteins that are specifically cleaved by neutrophil proteases and that may function as molecular bottlenecks in cell death, inflammatory signaling pathways, and immune responses to pathogens. To address these knowledge gaps we propose the following specific aims:Aim 1. Identification of molecular targets of cathepsin G mediated cell deathAim 2. Characterization of new mechanisms of inflammation regulated by serpins, neutrophil proteases, and their targets, notably in the context of SARS-CoV-2 infectionBased on strong preliminary findings from an unbiased proteomic screen, we will use our expertise in cell death, inflammation and infectious disease to generate new advances in the field. Using in vitro assays as well as genetically modified mouse models, we will test specific hypothesis in the regulation of inflammatory and innate immune responses that will shed light on yet unexplored path in cell death and uncontrolled cytokine responses.",,2027,Institut für Virologie und Immunologie IVI Sensemattstrasse 293 3147 Mittelhäusern,939349.8,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P28728,196062,Rapid Evaluation and Development of Cellular and Animal Tools to fight SARS-CoV-2,"At the end of December 2019, an outbreak of an unexplained viral pneumonia emerged in Wuhan, Hubei Province, China. The agent was identified as a new coronavirus that is currently referred to as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and is known as the etiological agent of Coronavirus Disease 2019 (COVID-19). Despite unprecedented public health measure by the Chinese and other governments to contain the SARS-CoV-2 outbreak, there are now over 300'000 confirmed cases reported worldwide and more than 14'000 deaths. Numbers continue to rise exponentially in many parts of the world despite rigorous global public health measures and state-enforced quarantine of whole communities and countries. There are currently no approved interventions such as antiviral drugs, vaccines and immuno-prophylaxis available that can be readily used as a prophylactic or therapeutic treatment to halt the current SARS-CoV-2 pandemic. The development of novel antiviral drugs, immunotherapies and vaccines against SARS-CoV-2 will have to be evaluated in pre-clinical animal models before being administered to humans as prevention or intervention strategies. To fulfill this major gap in the process of testing new therapeutic solutions and to increase knowledge in the pathogenesis of SARS-CoV-2, we propose the following specific aims: Aim 1: we will use an authentic in vitro model of the respiratory epithelium with air-liquid interface airway epithelial cells (AECs) to identify suitable domestic and wild animal models susceptible to SARS-CoV-2Aim 2a: we will revisit and improve the mouse model developed following for the SARS-CoV epidemic in 2002/2003 and investigate human ACE2 expressed under the endogenous mouse Ace2 promoter, as ACE2 is a shared receptor between SARS-CoV-2 and SARS-Cov. Both in vitro and in vivo approaches will be investigated.Aim 2b: we will develop new mice with altered activity of the TMPRSS2 protease, which enhances SARS-CoV-2 entry into target cells. We aim to identify conditions of improved infectivity in vitro that would lead to better mimic severe clinical COVID-19 symptoms in vivo. Approaches will include expression of hTMPRSS2, deletion of endogenous inhibitors and modeling chronic lung disease.Overall, our project will lead to novel tools for accelerated development of interventions such as antiviral drugs, vaccines and immuno-prophylaxis to halt the current SARS-CoV-2 pandemic outbreak. The developed tools will likely have a significant impact on understanding the pathogenesis of the virus and provide multiple options for much needed pre-clinical applications.",,2022,Institut für Virologie und Immunologie IVI Sensemattstrasse 293 3147 Mittelhäusern,325521.31,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P28730,200914,"Post-Pandemic Economic Outlook: Automation, Reshoring, Education, and Growth","The common theme of this project is the post-pandemic economic outlook, with special emphasis on automation, reshoring, education, and growth. Its main objective is to provide frameworks that combine cutting edge theories and methodologies stemming from various strands of macroeconomics to address questions related to how the strategies of future-proofing supply chains following the Covid-19 pandemic impact national and world economies.Reshoring, the relocation of offshore production back to the home economy, has been an evolving theme over the past couple of years. The reason is that the advances in automation make it possible for robots to replace some of the jobs that were previously offshored to lower labor-cost countries. The topic gained momentum recently due to the increased trade frictions between the United States (US) and China and the global supply chain disruptions triggered by the Covid-19 pandemic. However, there is little and mostly empirical research discussing the implications of reshoring for the source country, only some of these analyses being also motivated theoretically by deterministic models of production. In contrast to this literature, we will set up a dynamic stochastic general equilibrium (DSGE) model with endogenized growth that incorporates reshoring decisions, automation and technology adoption activities, unemployment, and public institutions. We will use this framework to analyze the impact of various policies taken in different countries in response to the Covid-19 pandemic. Further, we aim to make a horse race of automation, adoption, employee retention, and reshoring subsidies to investigate which has the best implications for employment and growth.Given its aim, this model allows for skill heterogeneity but assumes that the levels for the different skill groups of workers are exogenously provided. However, the occurrence of unemployment with technological change has been shown to depend on the extent to which workers can educate themselves (e.g. Mortensen and Pissarides, 1994; Carré and Drouot, 2004; Moreno-Galbis, 2012). For this reason, in a second paper, we relax this exogeneity assumption and allow for human capital accumulation. The purpose is to investigate the role of governments in equipping people with the right skills to meet the labor requirements in the age of automation. We will thus construct a model that facilitates the analysis of whether education and skill-upgrading subsidies can mitigate the negative consequences of automation and reshoring on low-skilled labor employment.In a third paper, we will switch focus to the offshore destination countries, for which the offshoring of business processes from developed countries has been a boon. The reason is that it brought significant economic benefits stemming from increased job creation and consequently from enlarged demand for goods and services. However, empirical research indicates that the acceleration of automation in developed countries leads to a decrease in offshoring and has a negative impact on employment in countries that are offshoring destination. We thus propose a framework to investigate how large the negative effects of a decrease in offshoring can be for the destination country and whether policy interventions through education, R&D, and automation subsidies in an offshoring destination country might reduce at least the long-term impact.Lastly, we will combine and extend the above-mentioned models to provide a workable modeling toolkit to analyze how the various business or government policies can influence offshoring, backshoring or nearshoring decisions and ultimately economic growth in Switzerland. In the past years, Swiss companies have mainly offshored, with some of them afterwards nearshoring their activities from Asia to Europe and only a few of them backshoring to Switzerland. The vulnerabilities of the global value chain exposed by the Covid-19 disruptions might encourage Swiss firms to reduce their offshoring and even choose to backshore. For this reason, it is important to investigate how several policy actions to improve technology absorption and top talent availability could influence these decisions and what will be their implications for the Swiss economy. Inspired by the success of the MONROE Toolkit (2019), to whose realization I also contributed, the policy modeling toolkit for Switzerland, while undoubtedly containing more complex models than those included in MONROE, will have a user-friendly interface which will make it accessible even to users without advanced modeling skills.",,2025,School of Economics and Political Science University of St. Gallen,237329.23,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P28736,198274,Development of a Radioligand for ACE2 PET Imaging - A Tool to Investigate the Expression and Regulation of the SARS-CoV-2 Entry Receptor,"Background: The severe acute respiratory syndrome cornavirus-2 (SARS-CoV-2, Covid-19) pandemic shows large variability in disease presentation, progression, and (fatal) outcome. Currently, the development of diagnostic assays for early detection of Covid-19 infection receives much attention, but the risk factors that determine disease severity and outcome are insufficiently addressed. Adequate early risk stratification will be essential to avoid overburdening hospitals and intensive care units in view of eventual second wave of the outbreak or future generations of SARS-CoV. Molecular imaging using Positron Emission Tomography (PET) may serve for risk stratification by quantifying the expression and regulation of key players of the disease, thereby providing personalized therapy options. PET agents have hardly been implemented in clinical research regarding SARS-CoV-2.Hypothesis: The angiotensin converting enzyme 2 (ACE2), the virus' entry receptor to the host cell, has been identified as a pivotal determinant of SARS-CoV-2 transmissibility. Recent findings suggest that the expression and regulation of ACE2 can be used as a biomarker for an individual's susceptibility for viral infection as well as disease progression and severity. Goal: The aim of this project is to develop a radioligand for non-invasive imaging of ACE2 using PET. This novel radioligand should serve clinicians as a tool to investigate the dynamics of ACE2 expression in response to age, gender, preexisting morbidity, medication and environmental factors and, thus, enable (early) risk stratification.Objectives and Approach: Peptides- and small molecule-based ligands targeting ACE2 will be developed for radiolabeling to enable non-invasive in vivo imaging of ACE2. The ligands will be synthesized using solid phase and conventional chemistry. Peptides will be modified with a chelator for radio-metalation, while specific precursors of small molecule-based ligands will be designed for radio-fluorination. The radioligands will be tested for chemical and biological stability, as well as ACE2-binding affinity and selectivity using ACE2-transfected cells. The most promising candidates will be evaluated in vivo using normal mice to determine the pharmacokinetics, xenografted mice for assessing ACE2-specific uptake and genetically-modified mice expressing the human ACE2 to determine the radioligand's potential for quantifying ACE2 expression using PET imaging.Scientific Value and Impact: Molecular imaging agents are essential tools to improve the understanding of a disease, its severity and progression. Successful completion of this research project will deliver a PET agent (peptide or small molecule) for non-invasive imaging of ACE2. Such radioligands will aid researchers to better understand the protein's expression, function and regulation in the context of Covid-19 infection and disease phenotype. The development of an ACE2-targeted PET agent is innovative, novel and may - when combined with existing and on-going projects of ACE2 determination - give insights in the dynamics of ACE2 expression which will be essential for the risk management of individual patients. An ACE2-targeting PET agent may also be utilized towards a better understanding of the ACE2's protective role in cardiovascular disease, which in turn presents the main risk factor for severe disease progression upon Covid-19 injection. Future Implementation: The rapid and cost-effective clinical translation of a novel ACE2-targeting PET agent is feasible due to the unique situation at the Center for Radiopharmaceutical Sciences, which allows production of radiopharmaceuticals under Good Manufacturing Practice (GMP). The investment of resources into the proposed project would serve a rapid development of an ACE2-targeting radioligand to provide physicians with this essential tool in the near future.",,2023,Paul Scherrer Institut,605877.57,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Pathogen morphology, shedding & natural history | Prognostic factors for disease severity | Disease pathogenesis",2020 +P28738,196217,Antiviral Protein Membranes for Air Purification,"Protein based membranes and membrane protein filtration devices have shown outstanding potential in the treatment of water and are already being industrially implemented in the purification of water from a large spectrum of organic and inorganic contaminants. Since the principles of filtering liquids (water) and gases (aerosol) share many common similarities, it is conceivable to expect that the same membrane could also serve in some specific aspects of air treatment. However, to date, treatment and purification of air streams using protein-based membranes has not been considered at all by the international scientific community. Here we propose to use protein-based membranes for the purification of air contaminated by COVID-19 and/or other respiratory viruses, and we aim at establishing a new technology which could ideally serve in the design of membranes for any type of virus inactivation.",,2022,"Institut für Lebensmittelwissenschaften, Ernährung und Gesundheit ETH Zürich",304594.63,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P28749,213191,Self-organized learning at secondary school. An investigation into inter-individual differences among students in dealing with learner autonomy,"The ability to independently acquire new knowledge and to regulate and organize one's own learning has become a key qualification in today's information society due to the rapid changes in knowledge. Their importance for school practice is currently being highlighted again due to COVID-19 and the switch to distance learning in many countries. Self-organized learning requires that learners become active designers of their own learning process. This study assumes that not all students know how to deal constructively with the autonomy expected of them in self-organized learning, as they differ both in terms of the necessary skills for self-regulation of learning (learning strategies, metacognition) and in terms of the motivational prerequisites for learning. The subject of the study is therefore inter-individual differences in self-organized learning among students, which are methodically examined using a sequential mixed-methods approach. Based on a quantitative sample of 1363 students from high schools in the canton of Bern, four learner types are formed using cluster analysis, which differ in their self-efficacy beliefs with regard to their subject-specific and interdisciplinary learning. This is followed by a qualitative in-depth study in which a total of 27 students of the various types were selected and questioned in focused guided interviews about their perception of self-organized learning and their ideas about teaching and learning. Finally, two maximally contrasting cases are selected and portrayed using quantitative and qualitative data. The results show that the four learner types differ significantly from one another, although not in all aspects examined. Significant explanatory power is attributed to a particular conception of learning, which is more evident in the type of successful learners: individuals of this type view learning as a challenge and an opportunity for personal development, accept that learning opportunities involve uncertainty, and at the same time emphasize that persistence is necessary for successful learning.",,2022,Institut Fachdidaktik Sprachen Pädagogische Hochschule St. Gallen,5904.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P28754,206818,Uncovering the non-canonical MHC class II receptor-usage of a newly discovered influenza A virus subtype in wild diving ducks,"Influenza A virus (IAV) is a seasonally recurring respiratory pathogen that causes epidemics in the human population with significant burden to health and economy. Despite having a considerably broad host range including humans, the main reservoir of IAV resides in wild waterfowl and shore birds. For this reason, zoonotic IAVs as emerging pathogens carry the potential to cause devastating pandemics.IAVs are classified by their immunogenicity of their surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Until today, there are 18 and 11 different HA and NA subtypes described, re-spectively. The HA, as a key determinant of the IAV host range, engages the host cell receptor and facilitates cell entry and infection, and is therefore a major focus of research. The most recently dis-covered IAV subtypes H17N10 and H18N11 in bats have not only expanded the IAV host range but also unveiled a novel mode of the IAV receptor-usage that is independent of the canonical IAV recep-tor sialic acid (SA), a sugar modification on host cell glycoproteins and glycolipids. During my PhD studies, I have discovered that bat IAVs exploit the major histocompatibility complex (MHC) class II from multiple species including humans, chicken, bats and pigs, as entry receptors. This finding has major implications for the host range of bat IAV and more importantly has revealed MHC class II as a non-canonical IAV receptor.The discovery of a novel IAV subtype in wild diving ducks in Northern California, provisionally termed HXNX, with properties reminiscent of bat IAV raised the question whether HXNX enters its host cells through MHC class II as well. My preliminary experiments support this hypothesis and indicate that HXNX does indeed not bind SA, but instead uses MHC class II as host cell receptor. These findings suggest a more widespread role for MHC class II as an IAV host cell receptor than initially thought.Based on these recent findings, I propose to uncover the non-canonical MHC class II receptor-usage of the novel influenza A virus subtype HXNX during my postdoctoral studies in the renowned influenza research laboratory of Prof. Adolfo García-Sastre at the Icahn School of Medicine at Mount Sinai (ISMMS), New York. First, I will examine the host range of HXNX by establishing entry assays using HX-pseudotyped virus-like particles (VLP) and test on cells expressing MHC class II from po-tential HXNX hosts, including different duck and bat species. Furthermore, I will work in collaboration with a global IAV surveillance center in the U.S. to determine the distribution of HXNX in duck and bat populations in Northern California. Second, I will generate and test chimeric MHC class II proteins of species that represent functional or non-functional HXNX receptors, which will enable the identification of the receptor-binding site of HX on MHC class II. Finally, I will establish the reverse genetics tools to rescue the recombinant HXNX virus, thereby generating the infectious HXNX virus for the very first time, which is essential to further investigate the biology of HXNX, including its pathogenicity and tissue tropism in vivo.Covering significant areas of influenza virus research, the proposed project aims at comprehensively studying a novel IAV subtype by assessing its host cell receptor-usage, a key determinant of the virus's host range, pathogenesis and tissue tropism. Moreover, the obtained results will underscore the role of MHC class II as a genuine IAV receptor used by multiple IAV subtypes, and thus will pro-vide profound insights into IAV biology.",,2024,Icahn School of Medicine at Mount Sinai,132571.32,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P28760,198403,"Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of critical SARS-CoV-2 infection in hospitalized patients with COVID-19: a randomized, parallel-group, openlabel, multi-center exploratory trial.","Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019 causing a worldwide pandemic of coronavirus disease 2019 (COVID-19). Systemic hyper-inflammation is a hallmark of severe stages of COVID-19 leading to acute lung injury (ALI), need for mechanical ventilation and ultimately death. The mechanism responsible for virus-induced hyper-activation of the host immune system remains to be fully elucidated. Unregulated complement system activation induced by CoVs plays a crucial role in the pathogenesis of acute lung injury in COVID-19. Similarly, involvement of the kinin-kallikrein system in capillary leakage and subsequent pulmonary angioedema has been suspected. In particular, a reduced activity of angiotensin converting enzyme 2 (ACE2) caused by SARS-CoV-2 leads to a relative abundance of bradykinin degradation products and local pulmonary edema. Lastly, over-activation of the contact activation system may be involved in the observed thromboinflammation. C1 esterase inhibitor (C1INH) is a potent inhibitor of these three plasmatic cascades and has been shown to reduce pulmonary inflammation and death in a CoV mouse model and in human studies of severe sepsis. Aims: To assess the safety and efficacy of recombinant C1INH (conestat alfa, Ruconest®) in addition to standard of care (SOC) in patients hospitalized with severe SARS-CoV-2 compared to SOC only.Hypothesis: Administration of conestat alfa for 72 hours in addition to SOC in patients with severe SARS-CoV-2 pneumonia is safe and associated with a reduced clinical severity on day 7 and a lower risk of disease progression to mechanical ventilation compared to SOC.Methodology: The PROTECT-COVID-19 trial is a randomized, open-label, parallel-group, controlled, multi-center clinical trial. Consecutive patients admitted with COVID-19 not requiring intensive care support will be randomized in a 2:1 ratio to treatment with conestat alfa for 72 hours in addition to SOC or SOC only. The primary endpoint will be the disease severity on the 7-point Ordinal WHO scale on day 7. Secondary endpoints include time to clinical improvement, the proportion of participants alive and not having required invasive or non-invasive ventilation and the incidence of ALI within 14 days after enrolment. Treatment safety and the activity of the above mentioned plasmatic cascades will be assessed. For a 2:1-randomization, a nonparametric analysis by the stratified logrank-test, and an adaptive group sequential analysis, the overall sample size is estimated as 120 = 80 + 40. Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels ap = 0.0221.Potential significance: Targeting multiple inflammatory cascades with conestat alfa early during COVID-19 is an innovative approach to prevent disease progression by ameliorating excessive (thrombo-) inflammation. Interventions that prevent deterioration and mechanical ventilation in COVID-19 are highly desired in a pandemic situation with limited ICU and ventilation support capacity. If treatment with conesta alfa proves to ameliorate pulmonary inflammation and injury, this may be relevant not only on an individual but also on a population level.",,2022,Kantonsspital Basel Universitätskliniken Medizinische Klinik 1,673782.46,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Clinical trials for disease management",2020 +P28764,196177,Anti-CoV: Full-cycle high-throughput infection screen to identify clinical compounds with high repurposing potential against COVID-19,"The ongoing human coronavirus (HCoV) pandemic and the associated COVID-19 disease caused by SARS-CoV-2 dramatically impact individuals and societies, putting the world at disruptive risk, and democracy under enormous stress. Rapid progress in identifying anti-viral compounds for human use is urgently needed to limit the impact of the crisis, and prepare societies against recurring SARS-CoV-2, and other viral outbreaks that can be even more devastating in the future. To identify anti-viral measures interdisciplinary research is required at all levels, from basic virology to applied drug and vaccine development as well as societal studies. An important strategy is to identify novel anti-virals that target the host rather than the virus, akin to cancer therapy. This strategy is expected to reduce viral drug resistance, and provide complementary targets against the disease. SARS-CoV-2 replicates in the upper respiratory tract to high levels, and progresses to the lower respiratory tract where it causes inflammatory responses and exacerbates lung disease, particularly in people with preexisting lung conditions, or immune disfunctions. The high virulence of HCoV is due to viral interactions with the host during entry, replication and egress from the infected cells, and leads to the production of viral factors antagonizing the protective effects of host immunity components, such as interferon. Strategies blocking the viral effects on the host have to be identifed, and rapidly implemented for use in humans. Host targeting against viral infections has been a focus of the Greber lab at the University of Zurich. More recently, a collaboration of the Greber laboratory and the Turcatti laboratory at EPFL has screened a chemical library of about 1200 compounds in an image-based, full cycle test with human adenovirus. This screen uncovered a clinical compound, the HIV protease inhibitor Nelfinavir. Here, we propose a three-step procedure to identify novel chemical compounds against the pandemic strain SARS-CoV-2. Step one is a high-throughput drug screen against HCoV infection in human cell cultures, using a customized library of 5480 clinical and preclinical compounds, many of which are used in humans against non-viral disease. The initial screen will be conducted with an attenuated HCoV at biosafety level 2 (BSL2), measuring all the major virus replication steps, including entry, replication, assembly and spread to uninfected cells. Step two will test anti-HCoV compounds for efficacy against SARS-CoV-2 at BSL3 (collaboration with University of Bern). Step three will consider the most promising compounds for applicability in clinical trials against COVID-19, and in-depth follow up studies. Funding for clinical trials will be seeked by separate grant applications. In summary, our approach to identify novel clinically approved compounds against SARS-CoV-2 is unique in that it explores the complete viral replication cycle by an image-based automated procedure in human cell cultures. It presents an outstanding opportunity with translational potential. The project will provide an extensive amount of fully open-access data, which will spur follow-up projects exploring the cell biological mechanisms and mode-of-action of the newly repurposed anti-viral drugs against the highly disruptive COVID-19 disease.",,2022,Institut für Molekulare Biologie (IMLS) Universität Zürich,330158.14,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P28765,196330,Directed search for host surface proteins as antiviral targets against SARS-CoV-2,"In late 2019 a novel coronavirus emerged in the human population in Hubei province, China from an unknown animal source. In four months, it spread to 190 countries and as of March 24th it infected more than 300'000 people worldwide, 15'000 of which with fatal outcome. Governments all over the world struggle to contain the pandemic, with never before experienced population-wide lockdown measures. Socio-economic consequences of this lockdown are not foreseeable yet. The virus, named SARS-CoV-2, is closely related to the 2002 SARS-CoV-1 and causes mild to severe respiratory symptoms and in severe cases viral pneumonia and death. Especially elderly patients are at high risk of severe disease progression with an elevated chance of mortality (15%) in consequence of coronavirus disease 19 (COVID19). Currently no vaccine is available and repurposing of antiviral drugs is still in an early stage. Thus, therapy is currently largely limited to support measures like oxygen and ventilation, if required. To address the Swiss National Fund Special Call: Coronavirus, we here propose a project, aiming to identify novel antiviral targets on the host cell surface. As all viruses, SARS-CoV-2 depends on host proteins for its replication. This affects every step of the viral replication cycle, including viral entry. As a bona fide receptor for entry ACE2 was identified, but cofactors of this receptor are currently not known. We propose here a strategy, which was already successfully tested to identify influenza A virus hemagglutinin host interaction partners on the surface of human lung epithelial cells, which were then targeted by chemical compounds to successfully reduce viral replication. Our strategy is based on soluble viral glycoproteins (S protein for SARS-CoV-2) fused to HRP. This fusion protein is stabilized by a trimerization domain to achieve the natural trimeric confirmation of the S-protein ectodomain. We will use insect cell produced SARS-CoV-2 S-protein-HRP as molecular bait, which, when attached to the host cell surface, mark host proteins in close vicinity by biotin ligation (proximity ligation assay). Biotinylated host surface proteins will be identified by mass spectrometry after streptavidin pulldown. Their role in early viral replication events will be confirmed functionally by genetic (siRNA or CRISPR/Cas9) or chemical targeting followed by infection with VSV-?G, pseudo-typed with SARS-CoV-2 S-protein. Our strategy is a directed approach to broaden the spectrum of antiviral targets, urgently needed in the development of novel antivirals to mitigate the current SARS-CoV-2 pandemic.",,2023,Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève,275172.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pre-clinical studies",2021 +P28767,204740,Strengthening Sequence Analysis,"Sequence analysis is one of the key approaches to study processes and trajectories from a life-course perspective. It provides a holistic view of trajectories by creating a typology that can be then used in subsequent analyses or simply to describe these trajectories. Despite its increasing uses in several disciplines, sequence analysis still faces several long-standing issues and limitations. This research project aims to address them to consolidate social science research making use of the methodology. More precisely, we aim to:•Develop a robust clustering and validation framework for sequence analysis that can properly handle weakly structured data or atypical trajectories and avoid sample dependence of the results.•Extend sequence analysis to handle large databases, which are increasingly common, by adapting typology creation and validation methods.•Conduct a critical theoretical and empirical simulation-based review of available cluster algorithms grounded on life-course relevant aspects before issuing clear recommendations to sequence analysis users.•Develop a proper methodological framework to study the relationship between trajectories and covariates to avoid drawing wrong conclusions linked to a) simplification implied by the use of a typology instead of individual sequences and b) estimation errors of a typology that can be expected when working with sample data.•Develop a proper framework to handle missing data in sequence analysis in conjunction with multiple imputation.•Review missing data-handling methods and document their respective strengths and weaknesses for missing data patterns commonly encountered in life-course research, such as in panel or retrospective data.•Demonstrate the added values of each developed method through convincing studies on school-towork transitions in Switzerland, first before, and then during, the COVID-19 crisis using the large LABB administrative database.•Diffuse all the reviewed and developed methods by making them available in widely used R libraries and by writing user-oriented documentation.",,2026,Institut de démographie et socioéconomie Université de Genève,488432.31,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2022 +P28786,209898,INtegrating loneliness mitigation measures in pandemic management plans: an interdisCiplinary in-depth expLoration of psychologically and ethically sUitable interventions to DecreasE social isolation [INCLUDE],"Introduction: It is widely acknowledged that the Covid-19 pandemic, and successive Coronavirus-related restriction measures, have caused serious disruption to ordinary lives and a deterioration in public mental health. Apart from illness and death, a distinctive mark of the pandemic has been disrupted social interactions, increasing social isolation and loneliness. Mental health consequences varied widely and were significantly dependent on an individual's unique social context. While the National COVID-19 Science Task Force (NCS-TF) proposed already in June 2020 that mitigation measures for main stress factors should be included among pandemic management plans (PMPs), in-depth research on concrete measures and on the ethical balancing between prevention of mental health problems versus prevention of virus spread remains scarce. Given the high diversity of how people cope with social isolation, there has recently been a growing recognition that the concept of loneliness captures best the difference between being alone versus lonely, and that loneliness and its mitigation (during and beyond pandemics) need to be at the center of much needed further research.Already before the pandemic, globally, between one fifth and a third of the world suffered from loneliness. In 2005, 26% of the Swiss population reported feeling lonely and by 2017 the figure had increased to 38% (above the global average of 33%). It is well established that loneliness is a serious health risk that affects both psychological and physical health. There is a vital need to include loneliness prevention and alleviation interventions (LPAIs) in PMPs. To do so requires not only thorough knowledge about feasible and available measures and their usefulness, but also a well-argued and well communicated psychologically and ethically sound balancing between measures, especially those measures that may alleviate isolation, but at the same time increase virus spreading. Taking loneliness into account in future PMPs will reduce the harmful psychological, physical and behavioral effects of social isolation measures, increase individual and social welfare, and enable more transparent and just strategies to reduce the burden associated with pandemics. Objectives and study parts: We will use a mixed methods approach to fill the existing research gap. The aim is to provide an in-depth exploration into the experiences of people affected by loneliness in order to identify types and justifications of loneliness prevention and alleviation interventions that can inform PMPs. The study has the following main objectives and study parts:1. Identify the broad types of interventions offered by different levels of society to counter loneliness. Utilizing a gold standard classification system, a broad review of the types of loneliness interventions offered during the pandemic will be identified. These include direct and indirect interventions offered by individuals, local communities, and society as a whole (state/canton interventions). These interventions, identified through desk-top research and focus groups with local social actors, will be addressed in the interview guide in part 2a and taken up in parts 2b and 3 of the study. 2a: Explore and analyze experiences of loneliness: qualitative explorative research will be conducted using semi-structured interviews with a purposive sample of ca. 30-40 participants (15-20 from French speaking and 15-20 from German speaking Switzerland) who experienced loneliness, focusing on at-risk groups identified in part 1 (e.g. young, single, or mentally ill persons and recent migrants). Questions will center on the self-reported impact of the pandemic on loneliness and will incorporate explorative questions around the types of interventions identified in part 1 of the study. Data collected in this part will be subjected to qualitative content analysis with a view to considering the self-reported impact of the pandemic on loneliness, and the perceived effectiveness of types of interventions identified in part 1 that were the basis for participant interview guides in part 2a of the study.2b: Use a quantitative approach (questionnaires, Swiss and Canadian data) to confirm the perceived usefulness - including how participants balance harms and benefits - of loneliness alleviation measures.3. Triangulate findings from the preceding parts and carry out an ethical analysis related to how the balancing of prevention of loneliness vs. virus containment does and should affect the choice of measures. Use a participatory Delphi approach to produce recommendations for policy makers on the types of loneliness interventions that should be included in PMP. Part 3 of the project will enable recommendations to be put forward for individual, local and national PMP that will be targeted at alleviating loneliness in future pandemics when significant disruptions of social contact become necessary. Results will be discussed with stakeholders during national workshops and international conferences and reported in various publications.Benefit: The project is highly beneficial as it will 1) produce practical recommendations for future PMP including a white paper for policy makers, 2) provide new much needed Swiss in-depth as well as quantitative data; it will 3) provide an analysis of the types of LPAIs identified in the literature as effective and will 4) benefit national and international academic and practical debates on better crisis management and increased individual and collective welfare.",,2026,Institut für Bio- und Medizinethik (IBMB) Universität Basel,426587.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Other secondary impacts | Policy research and interventions,2023 +P28787,211841,International Symposium: A Culture of Collaboration,"The Institute for Biomedical Ethics (IBMB) and its home institution, the University of Basel, have always been committed not only to carry out cutting edge research, but also to engage in broader discussions about research itself, how to ensure that it corresponds to the expectations of society and how to improve the environment of Switzerland as a place of research and innovation. The IBMB has been particularly committed to underlying the importance of creating a positive culture of open collaboration within academia and between academia and other collaborating institutions in the research environment - with a particular focus on the biomedical and healthcare sector. A culture of collaboration is not just efficient and convenient, but also part of an ethical commitment of research - and academic research in particular - to serve the common good, thus reinforcing the trust in science, which was extremely relevant in recent times during the pandemic. To enhance collaboration and data sharing, the IBMB has carried out (and finished this year) its NRP 74-based research project on barriers to and facilitators for data collaboration (grant number 167356).The importance of a culture of openness, data sharing and collaboration in the scientific field is has an extremely central ethical relevance for a number of reasons. Firstly, a great deal of research projects is funded through public money (e.g. by the Swiss National Science Foundation), thus making - although only indirectly through taxes - citizens and residents of Switzerland the true promoters of innovation and science. There is therefore an underlying ""social contract"" between citizens and researchers, whereby the former provide the money that allows the latter to conduct scientific research with a maximum degree of freedom and independence, but with the commitment to serve the public good. This can be achieved only if researchers are open and collaborative, rather than exploiting the scientific freedom that public funding gives them, in order to pursue personal gains, by being protective of the discoveries they make or the new methods they develop. Secondly, a culture of openness is key to maintain the trust in science, which is necessary for society to progress and thrive. If it is exposed that researchers refuse collaboration or deny others access to their ideas, data or even laboratories, in order to egoistically protect their own private interest, society will grow unconfident of the scientific community. This can be of great damage in moments like the Covid-19 pandemic, where scientists were making appeals to the population to listen to their advice as 'trusted' experts. In the research project that the IBMB recently conducted as part of the National Research Programme 74 (NRP74) on Smarter Healthcare, our team also discovered that the absence of a fully-developed culture of collaboration is one of the main obstacles that hinder the sharing of data in the Swiss healthcare and biomedical research sectors. Our study has shown that these sectors are often dominated by the existence of a protective approach of different institutions towards ""their"" datasets. Mistrust - or sometimes even simple diffidence, or lack of reciprocal contacts and informal exchanges - between institutions can be the cause why it is very difficult to merge data between different sources in Switzerland. This in a barrier to start important research in the medical sector (e.g. epidemiological or healthcare service research) and even to conduct public health surveillance or quality assurance studies. As the Swiss healthcare sector is committed to becoming more digitalized and datafied - see for example the recent report of the Federal Office of Public Health titled ""Das Datenmanagement im Gesundheitsbereich soll verbessert werden"" - the development of a culture of collaboration and openness with respect to health data exchanges is bound to become more relevant. Moreover, openness and collaboration with respect to data is also at the core of international scientific initiatives such as Open Data and Open Science, which have been supported also by the SNF. Funding agencies and academic institutions in Switzerland and worldwide need to reflect together on efficient incentives to increase collaborative attitudes.Last but not least, creating an environment of openness and collaboration in the research field has been a commitment of many researchers in Switzerland in the last few years. For example, Professor Peter Meier-Abt, former Vice-rector of the University of Basel and President of the Research Ethics Committee of the Canton Zurich has always been a promoter of these values. He insisted on their importance throughout his career and has given them particular relevance in several of his engagements, for example concerning the Swiss Clinical Trial Organisation (SCTO), SwissPedNet, and as one of the main promoter of the Swiss Personalised Health Network (SPHN). In the latter he put the idea of cooperation between hospital and clinical research centers - as well as the collaboration between researchers from different institutions - at the center of this initiative. For these reasons, the IBMB has decided to organize - in collaboration with the University of Zurich, the Research Ethics Committee of the Canton Zurich and swissethics - the international symposium titled the ""A Culture of Collaboration"". The symposium will be dedicated to the recent departure of Professor Meier-Abt, and it will offer an occasion to reflect from a ""meta"" perspective on what science, scientists, funders and academic institutions can (and should) do to improve collaboration and cooperation between them.",,2022,Institut für Bio- und Medizinethik (IBMB) Universität Basel,5226.16,Not applicable,Not applicable,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Unspecified,,,,,,,,,Unspecified,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P28793,198418,"A continuously updated meta-ecological study of the effects of the COVID-19 pandemic on mental health, alcohol/substance abuse and violence in the general population.","Deterioration of mental health (including alcohol and substance abuse and violence) are important adverse effects associated with the COVID-19 pandemic and lockdown and played a role in decisions about containment measures. Such important decisions need to be based on hard scientific evidence about the true prevalence of mental health problems and their association with the intensity and duration of lockdown. This information, however, cannot be provided by a single study. This is because the exposures of interest (characteristics of the pandemic and lockdown) apply to all participants enrolled in the same study. An international perspective is needed where studies from various places with different outbreak intensity, different response to the pandemic, and different population characteristics are compared with respect to their impact on mental health. The aim of this project is to explore an innovative way to provide reliable large-scale evidence about mental health during the COVID-19 pandemic and its association with the containment measures put in place worldwide. The specific objectives are to answer:1.What is the prevalence of mental health problems in the general population and subpopulations worldwide during the COVID-19 pandemic? 2.How are mental health problems associated with a) characteristics of the pandemic b) the extent and intensity of measures to contain the pandemic? And which population characteristics (e.g. sex, age, comorbidities, cultural characteristics) modify these prevalences?A third objective is, while answering questions 1-2 to3.Develop a generic evidence-synthesis framework to explore epidemiological associations that can be used to address current but also future crisis situations.We will create an interactive, online platform to present ""living"" summaries of evidence and associations that is continuously updated as soon as a new study becomes available.While answering an important question for the current pandemic, the project will create the methods, infrastructure and knowledge in place to answer any future emergency question that relates to public health.",,2022,Institute of Social and Preventive Medicine University of Bern,376665,Human Populations,Unspecified,Unspecified,Unspecified,Drug users,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P28798,222916,International organizations and the depoliticization of the world,"Debates on the (in)uselessness of international organizations during the COVID-19 pandemic such as the war in Ukraine recall the expectations that weigh on these institutions which nevertheless claim to ""not do politics"". This work takes this claim seriously and studies how very diverse international organizations put it into practice to ""depoliticize the world"". How do they go about it? Based on different case studies ranging from the management of the environmental crisis to the reform of the UN Security Council, this work analyzes the practices of expertise, the claims to neutrality and the play on the temporality of negotiations as markers of depoliticization. What leads an international organization to depoliticize the world? The work reveals three main logics of depoliticization which are part of a pragmatic posture, legitimation strategies and attempts to avoid responsibility. This book demonstrates that international organizations cannot be reduced to apolitical mechanisms established solely to facilitate international cooperation.",,2024,International Relations/Political Science Graduate Institute of International and Development Studies,3470.95,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2024 +P28800,201126,Predicting patient flow congestion using extreme value theory,"This project constitutes a thematic follow-up to the on-going project 'Predicting patient flow congestion using extreme value theory' (hereafter called the on-going project). The project is part of the new context of a world panic-stricken by the pandemic due to the SARS-CoV-2 and its disease COVID-19. At this major turning point for humanity, the goals of the project naturally extend the aims of the on-going project and the particular focus on virus-relatedpandemic congestion will be addressed. More specifically, the aims of this project are:-- to develop models for 'time to recovery' after a period of congestion by analyzing therelation between the duration of a congestion and its magnitude,-- to develop branching processes to explore the extremes of loads (staff and/or bed utilization) ow creating congestion at different units in the hospital,-- based on new risk management developments, to improve the predictability power ofthe 'Congestiometer' that has recently been implemented at the University Hospital ofLausanne (CHUV) and that serves as a measure of the congestion.To achieve these goals in a real hospital context, we will benefit from the new and valuabledatabase (with confidentiality assured according to the strictest standards) of patients testedfor COVID-19 from the CHUV in addition to the database provided by the CHUV emergencyunit.",,2024,HEC - Ecole des Hautes Etudes Commerciales Université de Lausanne,344149.04,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Health Systems Research,Disease surveillance & mapping | Health service delivery,2021 +P28808,198276,"A live, biologically-contained vaccine against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2)","In the last months of 2019, several cases of pneumonia caused by a novel coronavirus emerged in Wuhan, China. The virus was initially linked to animal-to-human transmission in local wet markets. Shortly after, however, the virus started to be transmitted human-to-human, resulting in its spread across China and at least 20 other nations. In February 2020, the World Health Organization named the virus SARS-CoV-2, while the syndrome was named coronavirus disease 2019 (COVID-19). The symptoms develop as a severe respiratory illness with significant mortality among the population at risk, as individuals over the age of 60 or those with pre-existing conditions such as diabetes, cardiovascular illness, or hypertension. SARS-CoV-2 is highly transmissible, even from asymptomatic infected individuals. The ability of SARS-CoV-2 to cause a pandemic disease within a short time, suggests that the development of a vaccine is of utmost importance for the control of this viral infection. Due to this urgency, several laboratories around the world started to work in vaccine development against SARS-CoV-2, with over 120 vaccines in the pipeline so far. These vaccines can be generally classified in four groups: i) virus vaccines (weakened or inactivated); ii) nucleic-acid vaccines (DNA or RNA); iii) viral-vector vaccines (replicating or non-replicating) and iv) protein-based vaccines (protein subunits or virus-like particles). In this proposal, we will design a vaccine platform to create immunity against SARS CoV-2 based on a novel technology recently published by our group. This technology differs fundamentally from the aforementioned four vacine groups that are currently under development elsewhere: we will use live recombinant spores of Bacillus subtilis, applied via the oral route, for the delivery of SARS-CoV-2 antigens. Once orally applied, the spores bypass the stomach barrier reaching the small intestine to germinate in the gut and develop into functional biofilms that express the antigens of interest as a fusion-protein with the abundant biofilm matrix protein TasA. Using this technology we have already successfully vaccinated dogs and mice, eliciting both humoral and cellular immune responses against the fluorescent protein mCherry, and also to paramyosin and tropomyosin from Echinococcus granulosus. Using this principle, we will work on two parallel strategies to develop a vaccine that will induce an immune response against SARS-CoV-2:1)We will use two different domains of the spike protein from SARS-CoV-2 as antigens, one encompassing the Receptor Binding Domain (RBD) from the S1 fragment and a second encompassing the highly conserved heptad repeat HR1 motif from the S2 fragment of the protein. The viral S-protein has been described as essential for cell entry via the receptor ACE2.2)We will also use the N-terminus domain of the SARS-CoV-2 Protein E as antigen. Protein E is a viroporin with ion channel activity, and has been implicated in multiple aspects of the viral replication cycle: from assembly and induction of membrane curvature to scission or budding and release to apoptosis, inflammation and even autophagy.B. subtilis is a safe, non-pathogenic bacterial vector, with an excellent record of human and animal use as both probiotic and food additive. The genetic manipulation of B. subtilis is straightforward, and the spores have remarkable resistance to heat and chemicals. Since our platform is based on live B. subtilis, in this proposal we will address an aspect that was not addressed in our previous research: the biological containment in a markerless strain (no genes providing antibiotic resistance). Biological containment is an important issue to crack in order to satisfy Swiss and European regulations and thus expediting the market introduction. The vaccine will be tested in a transgenic mouse model expressing a human ACE2 receptor. The technology to be developed in this proposal will solve several problems of the current enteric vaccination strategies: i) substantial reduction of operational cost since B. subtilis spores are exceptionally resistant to harsh conditions, with no need of a cold chain for storage or delivery; ii) production of vaccine doses does not require expensive equipment or complex media, making scaling-up simple and inexpensive for broader use, and importantly iii) the vaccine will be biologically contained. Once completed, we will benefit from a platform that can be easily adapted to rapidly create a vaccine against emerging viral pathogens, contributing to our preparedness for future pandemics",,2023,Virologisches Institut Universität Zürich,530502.71,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P28816,210152,The Covid generation: Identifying risks and protective factors for young people's pathways through the Covid-19 pandemic in Switzerland [CovidGen],"The pandemic has severely affected the wellbeing of young people in particular. It is of utmost importance to gain a better understanding of how and in which way this has happened in Switzerland and which mid-term consequences with respect to wellbeing can be observed (up to four years after the start of the pandemic). Moreover, given that the pandemic required a quick policy response, most programmes and initiatives for young people were implemented in an ad-hoc manner. As a result, we lack an overview and knowledge on which approaches worked well and whether they targeted the groups most at risk. However, to draw conclusions for the future such an overview is required to examine whether policies targeted the groups most at risk. Against this background, CovidGen aims to answer two overarching research questions: 1)To what extent did the COVID-19 pandemic affect wellbeing of young people in the medium term, what were the main drivers, the groups most at risk and which protective factors mitigated negative consequences for wellbeing?2)Were policy initiatives to support young people during the pandemic focussing on the groups most at risk, and what can we learn from them for future crises?CovidGen will address these research questions by means of a mixed-methods research design, with two work packages (WPs) each focusing on one of the two research questions. A main overarching aim of CovidGen is to bring together findings from statistical analyses on drivers of wellbeing during the pandemic with an analysis of whether policy responses focused on these drivers and the risk groups in interaction with relevant policy actors in the field, to foster young people's resilience in future pandemics.In WP1 we use a cutting-edge quantitative approach with a particular focus on causal inference. The main objective of WP1 is to shed light on the factors influencing young people's (aged 14-35) wellbeing during the pandemic and beyond (in the short-term during the pandemic, and in the medium term until 2024). Next to examining, with a cohort approach, whether the wellbeing of the cohort experiencing the pandemic was differently affected compared to a pre-pandemic cohort, we also examine two types of factors contributing to this (1) whether the well-being effect of the pandemic was different depending on the socio-economic position of the young people and (2) whether the well-being effect was driven by changes in social connection, in socio-economic position and changes in school and work situation during the pandemic. The main objective of WP2 is to provide an overview of the diversity of policy initiatives oriented at supporting young people's wellbeing over the course of the COVID-19 pandemic. We will bring together policies and programmes that focused on above mentioned protective factors and draw conclusions on whether they reached the groups most at risk and with respect to lessons learned for youth policy in the near future and in the context of a future crisis. This will be done by producing an inventory of policies and programmes targeting young people for four cantons, which will provide a detailed overview of how these policy responses have been developed, implemented and with which success. Complementing the documentary analysis with 25-30 expert interviews, we will identify the strengths and weaknesses of the selected programmes as well as the challenges faced, and lessons learnt during their development and implementation. Our results will be translated into recommendations for policy interventions targeting young people's wellbeing in the next few years and in the context of eventual future crises.CovidGen is strongly embedded in the policy field, as it has established a close collaboration with Pro Juventute and Pro Familia as project partners, and we will constitute a policy advisory board to facilitate the policy research of WP2 and to exchange with for the translation of the findings of both WPs into policy recommendations. Due to the close collaboration with these important stakeholders and policymakers in the field throughout the project, CovidGen will be able to implement and disseminate its findings in the most effective way. Besides the scientific output (four peer-reviewed articles for WP1 and one for WP2), we will deliver the database of the policy inventory (the CovidGen database) as well as a policy report integrating findings from both the quantitative analyses on how wellbeing of young people was affected and for which particular groups, and a synthesis of the policy response oriented at young people's wellbeing during the pandemic in the four selected cantons. This report will be presented and discussed in a public final symposium.",,2026,Fondation suisse pour la recherche en sciences sociales (FORS),516569.44,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Policy research and interventions,2023 +P28818,210027,"Child protection in times of Covid-19 and beyond: Countering the impact of stressors, constraints and uncertainties on families, professionals and organizations","While international studies suggest the coronavirus pandemic has increased the prevalence of child abuse and neglect worldwide and has compromised the performance of national systems of child protection, the situation in Switzerland remains largely unknown. Several studies have been published on the well-being of children or adolescents in Switzerland during the pandemic more generally, but no study has systematically analyzed trends in child abuse and neglect or thoroughly examined the functioning of national, cantonal, or regional systems of child protection during this time.The proposed project is intended to fill this gap by providing empirical knowledge i) on the challenges that a range of organizations connected to the child protection system have faced during different stages of the Covid-19 pandemic, ii) how they have dealt with these challenges within their organizations and at their interfaces, iii) how these responses were perceived by parents and children in the child protection system, iv) how clients themselves experienced and dealt with problems particular to a pandemic, v) what outcomes have been observed for these organizational and personal responses, and vi) what may be learned from these combined experiences to better prepare the system for the event of another health emergency-or more generally, another acute societal crisis-in the future.To achieve these purposes, the project combines six work packages. Work package 1 will deliver two separate systematic literature reviews, one on the impact of the coronavirus pandemic on specific domains within national systems of child protection, and another on recommendations for policy changes and resilience-building that have been proposed in the scientific literature. Work package 2 contains a comprehensive institutional survey in the child protection systems of two cantons in the German-speaking part of Switzerland and two cantons in the Romandy. The cantons will serve as case studies, and the surveys will collect data on the incidence of child abuse and neglect cases in the participating institutions before and during the pandemic, along with professionals' quantitative and qualitative assessments of challenges ob-served. In work package 3, interviews with management and frontline workers from selected institutions will provide an in-depth understanding of the professionals' experiences and the conclusions drawn from them, while work package 4 will examine the perspectives of caregivers and their children in three types of child protection interventions (""parenting guardianships"" according to Art. 308 para. 1 CC, intensive family support, and residential care). In work package 5, propositions derived from work packages 1 to 4 will be submitted to an inter-cantonal panel of experts, following a Delphi procedure. This will help to determine the generalizability of findings from the case studies with respect to other parts of Switzerland. Finally, in work package 6, a comprehensive research report will be written that organizes and interprets the empirical findings from a more theoretically driven perspective.The proposed study may identify gaps in service delivery during the Covid-19 pandemic and lead to the proposition of strategies for more effective prevention of child abuse and neglect and child protection interventions in times of health emergencies or comparable societal crises. By addressing researchers, professionals and policy-makers alike, it may contribute substantially to a more resilient system of child protection in Switzerland.",,2026,"Departement Soziale Arbeit Institut für Kindheit, Jugend und Familie ZHAW",479309.59,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28822,213289,Direct and indirect effects of SARS-CoV-2 on the brain - a translational approach to Long COVID Syndrome,"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) primarily affects the respiratory tract but can also cause neurological symptoms such as loss of smell and taste, headache or fatigue. Up to a quarter of COVID-19 patients, including those with a mild acute clinical course, develop long COVID syndrome (LCS), a complex condition with prolonged heterogeneous symptoms including fatigue, malaise, and cognitive impairment. It is not yet clear whether these persistent symptoms are due to direct or indirect effects of virus infection and whether the central nervous system (CNS) is directly involved. However, the increasing numbers of patients with LCS are raising public health concern. Therefore, more detailed studies in particular on the long-term effects of SARS-CoV-2 infection on the CNS are urgently required. Using the K18-hACE2 mouse COVID-19 model, we have shown that all virus variants apart from Omicron can be neuroinvasive and infect neurons without overt damage, but induce microglial activation and a mild non-suppurative encephalitis, suggesting a direct viral effect on the CNS; other studies also indicate a role of systemically induced neuroinflammation in LCS.The objective of the project associated with the research stay is to shed light on the potential mechanisms underlying LCS. The specific aims are to determine the transcriptomic, translational and pathological changes in the brain of SARS-CoV-2 infected mice, with a focus on the inflammatory response, but also considering the impact on the functional and metabolic state, with and without viral infection of the brain, and - in the former - before and with the presence of inflammatory cells.Transgenic (K18-hACE2) mice will be experimentally infected with SARS-CoV-2 variants (eg. Pango B, Delta, Omicron), sacrificed at different time points early and late, i.e. after clinical recovery, after infection, and subjected to an in-depth transcriptome, proteomics and neuropathological investigation on the brain. The occurrence of viral persistence as well as the effect of immunosuppression and antiviral treatments on neuroinvasion and neuroinflammation will also be determined. The results of the study will elucidate the direct and indirect effect of SARS-CoV-2 variants infection on the brain, both at an early stage after infection and after recovery from respiratory disease. They will provide insight into possible mechanisms and pathways involved in LCS and might give indications to key biomarkers that could inform future investigations in humans. The study is expected to direct future approaches towards the prevention and treatment of LCS and hence have substantial public health impact.",,2023,Institut für Veterinärpathologie Vetsuisse-Fakultät Universität Zürich,22202.59,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Disease pathogenesis",2022 +P28823,199111,Earth at its limits,"With the new special exhibition EARTH AT ITS LIMITS the Natural History Museum Basel (NMB) picks up a topic of great current interest and relevance: the human overuse of natural resources and its consequences. We aim at providing a platform to inform visitors, provide new insights and inspire to reflect, discuss and act. To this end I apply for the SNF AGORA rolling call funding scheme to help finance a section with interactive stations. This section shall allow visitors to understand key processes in nature and better place in context the role we humans play as natural beings.The (social) media report daily of environmental crises across the globe, ranging from climate change, deforestations, heat waves and melting glaciers, to the Covid-19-pandemics. This overwhelming picture of a vast number of singular problems blurs the broader insight that, in fact, there is a common denominator. They are all symptoms of deep human interventions into global natural processes and system. These have led to changed living conditions on this planet characterising a new earth time, the Anthropocene. While there have been other exhibitions on the Anthropocene, EARTH AT ITS LIMITS takes an explicitly different approach: we take the challenging global situation as an opportunity to transfer knowledge and fascination about the questions how nature works, why biodiversity is key, and what natural role our own species plays. Only if we understand our own role in nature can we make informed individual, political and societal decisions and changes, thereby adapting to the changing living conditions on our planet. EARTH AT ITS LIMITS will be in three languages (Main exhibition languages: German & English, in booklet: French) and consist of four main sections: 1) a prologue on natural diversity and the state of our planet, 2) a section on natural processes and the role we humans play in them, 3) a section on big issues of human impact on the environment, and 4) an epilogue introducing the human earth age (Anthropocene) and addressing the questions how we ended up here, how we may adapt and shape our future for a good life despite limited resources.This AGORA proposal focusses on part 2. Here we develop in collaboration with scenographers, graphic artists and illustrators interactive stations where the visitors can try out and learn about the carbon cycle and its varied paths, the water cycle and its necessity for life, the fact that natural systems are dynamic and can adapt by changing - provided there is sufficient diversity, and finally our lifestyle and the associated ecological footprint representing the pressure on ecosystems through our high-level demands for natural resources. A fifth intervention shows an ecosystem as a network of ecological interactions among organisms - one position being free for the visitor, representing us humans in the network. This view is a key take-home image to clarify that ecosystems are not mere assemblies of organisms, but complex (and fascinating) interaction networks. And we humans are not standing apart or above, but rather are embedded in these networks in a multitude of ways.",,2022,Naturhistorisches Museum Basel,37484.9,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Unspecified,,,,,,,,,Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission | Vector biology,2020 +P28828,198287,"Development of a targeted, adenoviral gene therapy platform for optimized delivery of SARS-CoV-2 interventions to the lung","1. Project summary. A novel human coronavirus, SARS-CoV-2, originating in Wuhan, China, has caused a worldwide pandemic of COVID-19 for which there is no existing vaccine or cure1. As a response, researchers are rapidly developing new strategies to elicit immunity against the virus and/or reduce infection rates before COVID-19 overburdens global healthcare systems. According to the World Health Organization (WHO) DRAFT landscape of COVID-19 candidate vaccines published on 13 March 2020, adenoviral-based vectors have been identified from several developers as candidate delivery platforms for COVID-19 vaccines2 and as of mid-May 2020, an (untargeted) Ad5 vector and an (untargeted) chimpanzee adenoviral vector are currently in clinical vaccine trials. Our research group has a core expertise in protein engineering and has developed a robust and highly versatile platform for generating engineered non-replicative, high-capacity 'gutless' adenoviruses (AdVs) that can be (1) retargeted to transduce specific cell subtypes using interchangeable adapters that target tropism to cell-surface biomarkers4,5, (2) used to deliver large payload(s) of up to 36 kb, such as secreted neutralizing antibodies (nAbs) and/or complex vaccine cocktails, (3) generated at high titers with extremely high purities (<0.00001% contamination of helper virus), unprecedented in the scientific literature, and (4) coated with an engineered 'shield' that reduced immune-based clearance due to pre-existing immunity to the vector6. Projects developing this system for applications in cancer therapy have been our primary focus to date; however, we believe the current global health crisis warrants the development of our technology for applications to combat and prevent COVID-19 and other pandemic diseases that synergize with other approaches being developed in the international scientific community. In this proposal, we aim to adapt our delivery platform for two applications to combat COVID-19: First, we aim to target adenoviral tropism to key antigen-presenting cell (APC) types in the human lung using our bispecific adapter system. We propose that retargeted viruses encoding SARS-CoV-2 vaccines could then be administered intranasally or intrapulmonary as aerosols and thus more efficiently target key cell types involved in developing robust mucosal immunity and memory responses against SARS-CoV-2 infection. Second, we aim to use the Ad delivery platform to infect airway epithelia with genes encoding secreted, neutralizing antibodies against the SARS-CoV-2 spike protein as a way to prevent infection and/or gain time, and thus reduce viral spread and transmission. Hypotheses. We hypothesize that bispecific adapters can be used to mediate specific infection of airway APCs by SARS-CoV-2 vaccine-encoding adenoviral vectors, enhancing mucosal immunity and eliciting higher protection, and (2) the adenoviral delivery platform can be used for airway-localized production of SARS-CoV-2 neutralizing antibodies to prevent or reduce viral spread at the site of infection. We will pursue aspects of both strategies on the onset of the project, focusing in on the promising approach as the project develops.Specific Aim 1. Development of adenoviral retargeting adaptors for biomarkers present on airway epithelial cells (AECs) and antigen presenting cell (APC) subtypes. From our existing pool of retargeting adapters, we have identified several in our portfolio that can already be applied in the mucosal SARS-CoV-2 applications described here (i.e. retargeting to HER3, FAP, CSFR1). As an additional aim, we will generate new adapters to target discrete populations of lung dendritic cells (DCs) and macrophages (Mf) for vaccine delivery applications (e.g. CD11c, CD206 and DEC-205).Specific Aim 2. Generation of high-capacity 'gutless' adenoviruses encoding SARS-CoV-2 vaccines and/or secreted neutralizing antibodies to block SARS-CoV-2 entry and propagation. We will generate retargeted and shielded 'gutless' adenoviruses to deliver two COVID-19 interventions: (1) we will encode a vaccine based on the SARS-CoV-2 spike protein to elicit an antiviral immune response and prevent viral entry, and (2) we will encode a secreted neutralizing antibody against SARS-CoV-2 that will be produced locally in the lung epithelia. Additionally, as more neutralization and vaccine approaches are described by, we will adapt our system to robustly deliver interventions developed by others to the optimal cell types and tissues in the lung. We are in contact with experts with whom we are planning to collaborate on developing our technology, including (1) Mario Roederer at the NIH National Institute of Allergy and Infectious Diseases who is an expert in vaccine immunology and respiratory mucosa immunization8,9, and (2) Michael Schindler at the University of Tübingen, who is a molecular virologist specializing in novel immunotherapeutic approaches against viral pathogens and equipped to test our approach in an S3 lab approved for experiments with live SARS-CoV-2.Specific Aim 3. Optimizing intranasal, aerosol-based delivery of retargeted adenoviruses. Our previous work with our delivery platform has focused on developing intravenous, sub-cutaneous and intra-tissue administration of retargeted viral particles. In collaboration with James Friend (UCSD), we will establish aerosol-based systems to delivery viral particles to the alveolar surface. As adenovirus exists naturally as a respiratory virus, it is well-suited for this route of administration10.",,2022,Biochemisches Institut Universität Zürich,432884.75,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P28845,201137,"Stressors, overall health and workplace wellbeing of Swiss nurses during the COVID-19 pandemic and potential health protective factors: A longitudinal mixed-method study","The COVID-19 pandemic had a heavy impact on healthcare systems in the spring of 2020 in Europe and most predictive models for the pandemic concur that a second wave is in the offing. Pandemics of the sort expose nurses to different types of stressor, such as having to perform unusual tasks in unusual settings, which may be associated with high levels of psychological distress. The majority of studies undertaken have taken a pathogenic approach to the subject. However, according to the WHO, health is 'a state of complete physical, mental, and social wellbeing, and not merely the absence of disease or infirmity.' The few studies that have taken a salutogenic approach to the subject have shown that nurses can retain their health despite a pandemic by mobilizing what is referred to as generalized resistance resources. It is extremely important to gain a better understanding of how nurses retain their health in the face of this type of epidemic situation. This information could then suggest leads for developing interventions aimed at maintaining their health and workplace wellbeing in the context of a pandemic. Against this background, we intend to undertake a study to understand how nurses working in Swiss hospitals retain their health and workplace wellbeing over the course of the COVID-19 pandemic by investigating the moderating effects of resources mobilized against stressors inherent to the pandemic situation. To this end, we will use a concurrent mixed-method panel design with qualitative interviews ancillary to quantitative analyses. Data will be collected at four time points: T0, to set baseline levels; T1, six months after T0; T2, 12 months after T0; and T3, 18 months after T0. Qualitative data (T1 and T3) will be collected through focus groups (FGs). The target population will consist of all nurses working in care establishments who have had direct, indirect or no contact with COVID-19 patients in several hospitals in the three linguistic regions of Switzerland. Results will serve to a) analyze change in nurses two years after exposure during the COVID-19 pandemic, b) analyze change in the effects of potential health protective factors and in nurse workplace wellbeing, c) develop new knowledge in an unusual context using a theoretical framework to guide analysis of how the concepts under study relate to one another, and d) develop solid new knowledge to be used to develop new preventive interventions to support nurses during a pandemic. These results could also be integrated in quality improvement processes at the participating care establishments and will help steer the development of healthcare worker support programs for disease prevention and health promotion.",,2023,Institut et haute Ecole de Santé La Source HES-SO,590046.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Secondary impacts of disease, response & control measures",IPC in health care settings | Indirect health impacts | Social impacts,2021 +P28846,212963,Viral efficacy of early combination antiviral therapy versus antiviral monotherapy in Immunocompromised COVID-19 outpatient: a randomized controlled pragmatic strategy trial (COMBINE study),"In the era of the omicron variant, the immunocompromised population is the main at-risk population for severe coronavirus disease 2019 (COVID-19). Several new early treatments administered within 7 days from symptom onset have been developed to prevent worsening to a severe disease in at-risk patients, such as direct acting antivirals (DAAs) (e.g., nirmatrelvir/ritonavir [nirmatrelvir/r]) and monoclonal antibodies (mAbs) (e.g., Evusheld). However, clinical trials have not included these fragile patients and current evidence on the effects of antivirals has been generated in populations with a robust immune system and therefore cannot be extrapolated. Combinations have the potential to lead to a better antiviral response and better clinical efficacy (individual benefit), but they also has the potential to reduce resistance and variant emergence by decreasing viral loads, infectivity, and the duration of viral shedding (public health benefit), especially in this vulnerable population. To date, these combinations have not been tested in the clinical setting.Therefore, we have designed in the clinical trial-experienced Geneva HIV unit (Principal investigator: Prof. Alexandra Calmy), a phase 2/3 randomized, controlled, academic clinical strategy trial to assess whether an early combination antiviral therapy of DAAs (nirmatrelvir/r 300/100 mg twice daily for 5 or 10 days) and mAbs ( tixagevimab/cilgavimab 300 mg/300mg, single injection) may improve viral, but also clinical efficacy, compared to nirmatrelvir/r alone for 5 or 10 days.The primary endpoint is a SARS-CoV-2 viral load cycle threshold (CT) <32 by real-time RT-PCR in nasopharyngeal swabs at day 10 after treatment initiation. There will be several virological (e.g., resistance and variant emergence under treatment, viral infectivity, viremia, duration of viral shedding) and clinical secondary endpoints, such as hospitalization, death, clinical symptom duration or World Health Organization (WHO)-defined post-COVID-19 condition rate, thus highlighting its translational essence. To attain these objectives, we will include 256 patients randomized in four arms of 64 patients that will be followed for 180 days. Follow-up will include virological, clinical and safety data. To reach our recruitment targets, which would be hardly feasible in Switzerland alone considering the specificity of the trial population, we plan to conduct the COMBINE trial both in Switzerland and in France. This will be a unique occasion to gather the expertise of those in the fields of COVID-19, immunocompromised patients and clinical trials, including clinical, virological and methodological experts. The trial will be fully academic as study drugs will be obtained through the public health circuit for the routine use of antiviral SARS-COV-2 medication.This proof-of-concept study will bring novel important clinical data not only about the viral efficacy, but also about the clinical efficacy of combination antiviral therapy. If combination therapy is proven efficient, it may support a change of standard of care in the early treatment of this fragile population in order to improve virological and clinical outcomes. In terms of public health, an effective antiviral strategy may promote a new prevention tool against future SARS-CoV-2 variants and resistance that are more likely to emerge from immunocompromised patients. Finally, the COMBINE study will add crucial information on how to protect, care, and monitor patients with an underlying immunosuppression and with COVID-19.",,2026,Service de Maladies Infectieuses HUG,605307.07,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2022 +P28847,213919,Viral efficacy of early combination antiviral therapy versus antiviral monotherapy in Immunocompromised COVID-19 patients: a randomized controlled strategy trial: the OPTICOV study,"Immunocompromised patients are a vulnerable population, less likely to be vaccine-responders, largely underrepresented in COVID-19 outpatient clinical trials, and overrepresented in ICUs worldwide. They have a higher viral load and a prolonged viral shedding, with often persistent infection. This results in a higher probability of variant selection, suggesting a particular interest for early antiviral strategies in this population, including monoclonal antibodies (mAbs) and/or direct active antivirals (DAAs). Treatment optimization has been truly transformative for viral diseases such as HIV or HCV and only achieved when antiviral drug combinations became the mainstay. Increasing treatment duration is another promising strategy. So far, no clinical trial has assessed the efficacy or safety of a combination of mAbs and DAA or of increasing treatment duration in COVID-19 immunocompromised patients.The main aim of this randomized factorial superiority phase 2/3 open clinical trial (OPTICOV) is to assess whether a combination antiviral therapy of oral DAA and mAbs compared to DAA monotherapy and whether an increase in DAA duration from 5 days to 10 days may improve viral efficacy in immunocompromised patients. To date, the best available DAA is nirmatrelvir/r (nirm/r) (2*300/100 mg/day for 5 days, orally) and tixagevimab/cilgavimab (T/C) (300/300 mg) the best mAb when considering BA.2 omicron subvariant predominance.Virtually, the four treatment arms will be: nirm/r 5 days + T/C; nirm/r 10 days + T/C; nirm/r 5 days alone; nirm/r 10 days alone.We will use a virological primary endpoint, with a recognized cut-off for infectiousness: SARS-CoV-2 viral load <32 CT by real-time RT-PCR in nasopharyngeal swabs at day 10 after treatment initiation. Viral load magnitude and duration predict clinical severity and are associated with infectiousness. Most efficient DAA treatments resulted in a significant viral load decrease. Thus, virological endpoints have the potential to be a surrogate marker.Secondary objectives and endpoints will be virological (assessment of the ability of combination therapy to decrease infectivity, viremia, viral rebound or the emergence of new variants/resistance at several timepoints) and clinical (assessment of the ability of combination therapy to increase the recovery rate, the 11-point WHO clinical progression scale score, and to decrease the rate of post-COVID-19 conditions by day 90).We will include immunocompromised patients aged 12 years or over and >40 kg, with asymptomatic or mild/moderate COVID-19 during the first 7 days of symptoms and no contraindication to each study drug. Standardized operating procedures will help investigators to assess if drug-drug interactions may contraindicate nirm/r. They will be followed over 90 days with 7 study visits (by phone or on site) after randomization.With 254 patients, we will be able to show a difference between both arms, assuming an incidence of the primary endpoint of 40% and 60% in combination vs. monotherapy and 10 days vs. 5 days, with a study power of 90% and an a risk of 5%. With this number of patients, we will be able to detect differences in clinical endpoints with sufficient power.The primary endpoint will be compared between study arms according to the intent-to-treat population using a log-log complementary model adjusted for the presence or absence of combination therapy for DAA duration and factors known to be associated with SARS-CoV-2 positivity.This proof-of-concept study will bring novel important clinical data not only on the viral efficacy of combination antiviral therapy, but also on the clinical efficacy. If combination therapy is proven efficient, it may support a change of standard of care in the early treatment of this fragile population. In public health terms, an effective antiviral strategy may promote a new prevention tool against future SARS-CoV-2 variants and resistance that are more likely to emerge from immunocompromised patients.",,2022,Service de Maladies Infectieuses HUG,3074.77,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2022 +P28848,196251,Efficacy of same day chemoprophylaxis for exposed asymptomatic individuals exposed to SARS-CoV-2 in Switzerland: a pragmatic open-label cluster randomized trial (COPEP-trial),"Background: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) is a novel coronavirus strain that was declared a pandemic by the World Health Organization on 11th March 2020. The world is now scrambling to identify effective pharmacological candidates for its prevention and treatment. The availability of simple and effective post-exposure prophylaxis (PEP) to prevent either SARS-CoV-2 infection and/or resulting clinical Coronavirus Disease (COVID-19) will play a crucial role both for the rapid containment and to protect at risk individuals including front-line health care workers now and in future outbreaks. Objectives We propose to assess the efficacy, safety and acceptability of same-day LPV/r-based and HCQ-based PEP compared to standard of care for asymptomatic individuals exposed to individuals diagnosed with SARS-CoV-2 in a category B open-label cluster randomized clinical trial. The study has two co-primary endpoints; 14-day incidence of clinical COVID-19 and 14-day incidence of PCR-confirmed SARS-CoV-2. Method: Participants will be screened if they had a close contact of newly diagnosed SARS-CoV-2 index cases as early as possible and randomized no later than 48 hours after the document contact. Adults without fever or respiratory symptoms will be enrolled across two sites, Geneva and Basel. During baseline visit, naso-pharyngeal swab, SARS-CoV-2 serology (rapid test) and a clinical assessment will be performed and individuals will be randomized by household 1:1:1 to either LPV/r 400/100 mg twice daily for 5 days versus a single dose of 800mg HCQ versus no treatment. Individuals will be asked to record daily their temperature and complete a online symptoms and adverse events questionnaire during the 14 days of follow-up. Participants who record COVID-19 symptoms will undergo clinical assessment and a naso-pharyngeal swab to confirm/exclude SARS-CoV-2 infection, and if found positive will be provided with appropriate care. Follow-up visit at Day 14 will include a naso-pharyngeal swab and completion of questionnaires on adherence and acceptability of the PEP intervention.Endpoints: This trial has two co-primary endpoints: a) 14-day incidence of COVID-19 in individuals exposed to SARS-CoV-2 who are asymptomatic at baseline (intention-to-treat (ITT) analysis)b) 14-day incidence of SARS-CoV-2 in individuals exposed to SARS-CoV-2 who are asymptomatic and PCR-confirmed SARS-CoV-2 negative at baseline (modified ITT)Secondary endpoints:a) severity of clinical COVID-19 (0- asymptomatic or with mild disease; 1 - hospitalized or died)b) adverse events c) adherence to and acceptance of PEPStudy impact and importance: COVID-19 generates intense pressure on health systems across the world, with the sudden and uncontrolled influx of severe cases causing depletion of all hospital-based resources. Meanwhile, asymptomatic SARS-CoV-2 infections fuel the pandemic. A simple and effective PEP strategy, that can be prescribed the same day with limited laboratory exams, will help contain both the current pandemic and future COVID-19 outbreaks. Even if effective vaccination and treatment become available, PEP will play an important role in safeguarding individuals at highest risk, including front-line health care workers, and will be crucial for rapid containment of future outbreaks. The PEP candidates we are proposing to investigate are cheap, safe and globally available, including in Switzerland. This makes them particularly attractive PEP candidates worldwide, including settings where health systems are fragile and the scarcity of tertiary care facilities, intensive care bed and ventilators cause concern in face of COVID-19.",,2022,Service de Maladies Infectieuses HUG,308261.77,Human Populations,Unspecified,Adults (18 and older),Urban Population/Setting,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Phase 3 clinical trial | Prophylactic use of treatments",2020 +P28857,209958,The practice of family law during the Covid-19 pandemic: Digital justice and gender inequalities,"This project aims at investigating the practices and challenges associated with the shift to digital justice during the COVID-19 pandemic in family proceedings in Switzerland with a special focus on separations and divorces. The impact of the pandemic has been especially drastic in family law with countless individuals caught up in the middle of a critical family crisis. In particular separating and divorcing individuals with minor children who were already in a situation of instability experienced increased vulnerability both materially and emotionally with detrimental yet differentiated consequences for mothers, fathers and children. Two legal issues were especially at risk of leading to exacerbated gendered inequalities and conflicts due to a reinforcement of traditional gender roles: child visitation and physical custody arrangements, and maintenance payments.To avoid delays and to deal with emergency cases, the Swiss Federal Council opened up the use of remote hearings in civil proceedings (COVID-19 justice and procedural law ordinance, RS 272.81) as other countries did. While digital justice holds several advantages (e.g. speed, cost reduction), it also raises a number of practical and ethical concerns (e.g. technology, confidentiality). Given the federal organisation of the Swiss justice system, recourse to remote hearings and associated social distancing measures were uneven across the different cantonal civil courts. As proximity to the persons concerned has been considered as a key advantage in family law, these changes presented a critical challenge. In this context, judges and lawyers were positioned at the frontline and had to quickly adapt their practices to prevent family circumstances of their litigants/clients to worsen and to find solutions acceptable for all parties.Thus, our overarching research question is the following: Under what conditions can digital proceedings ensure access to justice for separating and divorcing couples with minor children during a major social crisis such as the COVID-19 pandemic and mitigate the increased risk of gender and social inequalities? This main question is divided into three dimensions. The first dimension tackles the gender and social inequalities related to access to justice. The second dimension tackles gender and social inequalities related to visitation and physical custody arrangements. Finally, the third dimension tackles gender and social inequalities related to maintenance payments to children and ex-spouses. We hypothesize that there is a learning process both at the institutional and individual levels. At the institutional level, civil courts practicing family law had to change their protocols to implement the ordinance. At the individual level, judges and lawyers had to develop strategies to deal with separating and divorcing couples with minor children. This project has an interdisciplinary sequential mixed-method design that has already been successfully applied in a SNF research project conducted by the three main applicants (n° 100011_182364 / 1). It consists in a legal text study of the implementation of the ordinance RS 272.81 in Switzerland with an international comparison (work package 1) coupled with a qualitative study with a case study of court practices (work package 2) and a quantitative study using a questionnaire addressed to family judges and lawyers (work package 3).This interdisciplinary project linking law and sociology will simultaneously investigate legal and family consequences. The ultimate goal is to identify good practice examples to draw up recommendations useful for law makers and practitioners dealing with separation and divorce, and for the development of digital justice in Switzerland including amendments to the Swiss civil procedure code. In parallel, an offer of continuing training will be developed for practicing judges and lawyers, as well as for law students and other practitioners dealing with separation and divorce. This project will be critical to deal with the aftermath of this pandemic and to draw lessons for other types of crises and in time of stability.",,2026,Département de droit civil Faculté de droit Université de Genève,443649.05,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28863,204575,"Helpline Calls, Job Finding, and Interview Training in the Covid-19 Crisis","The Covid-19 pandemic has inflicted a lot of mental and economic pain on the world. Both the illness itself, and the fear of contracting the illness generate distress, but so do the lockdown and social distancing measures to contain the spread of the virus. As vaccines against the virus are becoming available, the immediate and most important consequences of Covid-19 on health systems could soon be averted, but key challenges remain. This project proposes new evidence on the role of policies vs the illness in shaping mental health, and how information and cognition training support job finding in a labor market scarred by the crisis. The first challenge is deteriorating mental health in many countries during the crisis, and the public debate does ascribes this to the measures to contain Covid-19. The first work-package on how Covid-19 and policy measures to contain its spread, or cushion its economic ramifications, affect calls to 33 helplines, operating in 24 countries located around the globe. Helpline calls are triggered by distress, and the number of helpline calls, as well as the reasons for calling can be used to gauge the state of mental health of nations in real time (Brülhart and Lalive, 2020). We provide novel evidence on the effects on helpline calls due to Covid-19, to the measures to contain the illness, and economic support to cushion the effects of lockdown measures. Disentangling these impacts is challenging in the context of one country, but our research is based on novel data that we hand-collected from over 35 different helplines around the world. The second challenge is unemployment which has increased by more than 50% from the onset of the crisis, and is bound to remain high for a longer period. Many job seekers suffer from deteriorating mental health, and Covid-19 could make employment trajectories less secure, and demand adaptation of their skills. The second work-package outlines an ambitious large scale, randomized field experiment, to be implemented in major regions of Switzerland, to understand how to assist job seekers in finding employment through actionable information to look for jobs, and training of cognitive functioning to improve multi-tasking and resilience to heighten the capacity to absorb information. This field experiment addresses the fact that job seekers are often not aware of their skills, or can not easily translate fine grained information on their skills into an actionable strategy for job search. Combining information with cognitive and stress resilience support is novel, and has the potential to provide strong impacts. The third work-package provides job seekers with training for conducting job interviews online. Job interviews are the first and most important step to securing a job, but the large majority of job interviews are conducted online. Conducting job interviews online introduces a burden on the interviewer and on the interviewee (Aparna et al, 2020). Online interview training could improve job seeker's online interviewing skills and chances on the labor market.",,2025,Département d'économie (DE) Faculté des Hautes Etudes Commerciales (HEC) Université de Lausanne,641474.12,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2022 +P28869,210180,"Drivers, impacts and interrelationships of cantonal policies and firm behaviour during the pandemic years in Switzerland","The goal of this project is to better understand and to quantify the interactions between Swiss federal and cantonal health and economic policies during the Covid-19 pandemic and their impacts on the well-being of firms in Switzerland. We collect and analyse data on non-pharmaceutical measures and fiscal support policies to analyse the type and speed of reactions of cantonal governments to the local health crisis. We will measure behavioural changes of different population groups in response to the health measures using mobility data. We will identify the determinants of different policies using panel-econometric methods that deal with direct and indirect spatial effects while controlling for time-location fixed effects.We will also evaluate the impacts of cantonal fiscal Covid-19 policies on firm expectations, survival, and other measures of firm well-being. We aim to disentangle supply- from demand-side effects by exploiting spatial and time variation in fiscal support. For example, the design of the federal credit program introduced exogenous variation in loan supply across cantons. There is also variation in the timing, size, and beneficiary sectors of cantonal fiscal support measures and differences in the sectoral composition of cantonal production networks.These analyses will enable us to improve our understanding of the mechanisms behind and the consequences of the Swiss federal system on firm outcomes. The goal of the project is to offer guidance to policymakers on how to improve policymaking in crises situations to preserve prosperity and welfare as much as possible in future crises while minimizing state expenditures and avoid unintended side effects.",,2026,"KOF Konjunkturforschungsstelle Department of Management, Technology and Eco ETH Zurich",350349.9,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P28871,204507,"The Politics of Public Health Threat. Exposure to Covid-19, Emotional Responses, and Attitudes towards coping with In- and Outgroups","Existing research on the consequences of a high prevalence of infectious diseases shows that a public health threat is related to an increased aversion and avoidance of unfamiliar and out-group targets and to a strengthened cohesion with familiar and in-group targets (Ackerman et al. 2018: 3). Nevertheless, in the absence of real-world data from pandemics, our present knowledge is based solely on artificial experiments, indirect measurements, and rather abstract macro-indices of pathogen stress. Against this background, the starting point of our project is the observation that the outbreak of the Covid-19 pandemic has provided the unique opportunity to evaluate the influence of exposure to a real public health threat on attitudes towards coping with in- and out-groups. Tying together the insights of the behavioral immune system hypothesis with standard political science models of emotional processing, the central focus of the planned project lies in three questions: (1) How does the Covid-19 threat experience shape the formation of socio-political attitudes related to the aversion and avoidance of unfamiliar and out-group targets and the cohesion with in-group targets? (2) What emotional responses does exposure to the Covid-19 pandemic trigger and how are these reactions responsible for the formation of these stances? (3) Which conditions shape the impact of the Covid-19 threat experience on attitudes towards coping with in- and out-groups? In answering these questions, the project radically departs from familiar research traditions of pathogen threat analysis. First, the envisaged project provides new empirical evidence relying on real-world data. Rather than operating with indirect instruments, the project relies on real-world experiments and actual data of the Covid-19 pandemic at an individual and contextual level. Second, the project develops new theoretical arguments. Existing theories are mostly tailored to analyze the impact of disgust as a pathogen avoidance-oriented emotion while widely neglecting other emotional experiences. This project aims to study emotions more broadly. Third, our study develops new policy recommendations. Based on the analysis of unique panel data and cross-national and sub-national comparisons, we learn which measures are best suited to moderate the effects of the Covid-19 threat experience. To access the above-mentioned research questions, we base our statistical analyses on already existing data. The applicant conducted four surveys involving 24,000 respondents (April/May 2020; late November 2020 to January 2021, April/May 2021, January/February 2022) in six European countries (France, Germany, Italy, Spain, Switzerland and the United Kingdom). Moreover, own panel data for Switzerland between April and October 2020 (3 waves; between 600 and 1,800 respondents) has been compiled. This database is supplemented by experimental studies conducted in March 2020 and March 2021. Beyond the Covid-19 related data, all these data sets contain numerous items concerned with the relevant questions of the research endeavor. The project will be carried out by the PI and one post-doctoral student, supported by a student assistant. Together, we strive for publication of articles in leading international journals covering varying aspects. Moreover, the objective is to publish a synthesis of research findings in an encompassing book monograph with a leading international publisher.",,2026,Institut für Politikwissenschaft Universität Bern,261936.33,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Other secondary impacts,2022 +P28875,221968,Comparative Analysis of Host Immune Signatures of Influenza and SARS-CoV-2 Infection vs. Vaccination: A Prospective Multi-Cohort Study of Host Transcriptional Responses including Single Cell RNA-Sequencing,"Background and Rationale. Host transcriptional immune changes in response to infection and vaccination, known as mRNA signatures, are novel diagnostic and predictive tools in the field of Infectious Diseases (ID), acting as a ""proxy"" for the immune system activity at a molecular level. Several signatures have been proposed to differentiate bacterial from viral or other infections, detect specific pathogens, and even predict disease severity and treatment outcome, serving as potent biomarkers of disease. Similarly, pre- and post-vaccination signatures to predict vaccine efficacy and immune memory are currently being studied, offering new insights into vaccine immunogenicity. The identification of such complex biomarkers can only be achieved using sophisticated molecular and bioinformatics analyses enabling high-throughput profiling of massive amounts of data. Comparing immune signatures between infection and vaccination can lead to the development of valuable, clinically relevant predictive tools. It can also shed light on immune responses associated with protection and durability for vaccine development purposes, and accurately differentiate breakthrough infection from vaccine-specific immune memory in antigen-exposed hosts for diagnostic and prognostic purposes. To date, such comparative data are lacking and could be generated by combining bulk transcriptomics with single cell RNA-sequencing (scRNA-seq) profiling of immune responses.Overall Objectives and Specific Aims. The aim of the proposed project is to identify common and unique mRNA signatures between infection and vaccine response to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using bulk transcriptomics and scRNA-seq data. To achieve this, we will define the temporal immune response to infection and vaccination, and explore whether signatures of successful vaccine response resemble those of pathogenic infection. Additionally, we will perform bulk RNA-seq cell deconvolution using scRNA-seq analysis to infer the cell types that contribute to signature performance and improve interpretability of the results.Methods. We propose a prospective, observational, multi-cohort study using array-based and RNA-seq data (referred to as transcriptomics) from blood samples of nearly 2,000 participants enrolled in studies included in the Human Immunology Project Consortium and the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC). Blood samples are collected at baseline (day 0) and at days 3, 7, 14, 28, and 29-70 following infection or vaccination. Through a standardized computational pipeline, we will identify and perform comparative analysis of mRNA signatures using differential gene expression (DGE) and B cell receptor (BCR) profiling on bulk and scRNA-seq data to identify novel, common, and unique signatures between infection and vaccination for influenza and SARS-CoV-2. Furthermore, we will match bulk and scRNA-seq data to perform bulk RNA-seq cell deconvolution and improve the resolution and interpretability of bulk signatures.Expected Results and their impact for the field. We aim to identify and compare common immune signatures between influenza and SARS-CoV-2 infection versus vaccination, with temporal response being the key component. The established global framework and analytical pipeline will promote reproducible methods for comparative signature discovery, making them accessible to the wider scientific community. In addition to developing new signatures that could be implemented as clinically relevant biomarkers, this project will expand current knowledge on immune pathways involved in the response to infections and vaccines, facilitate the development of models transferable to various settings and pathogens, and lay the foundation for subsequent human studies.",,2026,Department of Psychiatry Yale School of Medicine,143465.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,United States of America,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2024 +P28876,222955,The institutional communication during the pandemic in Ticino and Grisons,"This volume presents the results of a research focusing on the quality of Swiss institutional communication in Italian during the Covid-19 pandemic, with a focus on the Cantons of Ticino and Grisons. After some introductory notes by Ticino's political authorities directly involved in the communication to citizens, the volume is divided into three thematic sections. The first, dedicated to regulatory texts, addresses with two contributions the language of federal and Ticino Covid-19 legislation. The second section focuses on clarity of texts with information purposes (FAQs, press releases, fact sheets), also taking into consideration easy-to-read texts produced by Pro Infirmis. The third section explores, on the one hand, the language of institutional social media in Ticino and Grisons used by authorities during the emergency; on the other hand, it tackles the way the pandemic was reported in newspapers and on television.",,2024,Seminar für Italianistik Philosophisch-Historische Fakultät Universität Basel,16536.54,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2024 +P28877,203450,"Multi-scale mathematical modelling of pathogen, drug and vaccine interactions: optimising public health and disease elimination strategies","Quantitative sciences and mathematical modelling are increasingly important to understand existing and emerging diseases, and to plan the interventions to tackle them. Models that capture detailed biological, epidemiological and health systems factors, and the complex interactions between, can provide insight into the factors which drive disease dynamics. We have shown that mathematical models can be used to predict the impact of disease interventions; to define the desired characteristics of a new intervention; and to identify optimal deployment strategies. As we move towards elimination of malaria and other diseases, mitigating resistance to current interventions becomes crucial. Since the dynamics of resistance differ between high- and low-prevalence settings, mitigation strategies are likely to change as we get closer to elimination. Defining and quantifying these strategies for different settings and understanding how they differ as pathogens evolve is therefore essential.In the current global pandemic, we are at a crucial moment to define strategies for vaccine rollout. SARS-CoV-2 has shown a high propensity for mutation, posing the danger that new vaccine-resistant variants may evolve. The proposed project directly examines the dynamics of resistance evolution, and will define strategies for vaccine deployment that mitigate vaccine resistance. Our work will bring theoretical modelling and disease evolution understandings directly to bear on public health policy and vaccine deployment strategy in Switzerland.Proposing disease models with sufficient detail to evaluate disease interventions presents significant computational challenges for model simulation and sensitivity analysis on one hand, and methodological challenges for model calibration on the other. In phase 1 of the grant we developed machine learning based approaches to solve both these issues. In this prolongation we will adopt our methods to build detailed within-host models of malaria parasite dynamics, and adapt existing individual based models of malaria and COVID-19 to explore evolution of vaccine and intervention resistance.In Objective 1 we will apply our novel approaches to build within-host models designed to be sufficiently expressive to tackle resistance, and designed with parameterisation to sparse data in mind.In Objective 2 we will use global sensitivity analysis and the new models to determine key implementation and disease factors driving emergence and spread of malaria genotypes resistant to vaccines, monoclonal antibody therapies, and the spread of mosquitos resistant to insecticide-based interventions.In Objective. 3 we will adapt our methods from Obj. 2 and our existing individual-based COVID-19 model to determine the key implementation and disease factors driving the emergence of new vaccine-resistant variants of SARS-CoV-2.We will bring these results together to guide strategies for interventions, for disease control and elimination, especially in the context of resistance. We will promote integration of our model-based research findings into decision making. The proposal builds on the applicant's previous research and links basic science innovation through to application via new mathematical models, and thus will deliver significant advances for epidemiological modelling and understanding of resistance and disease evolution. While immediately relevant to malaria and SARS-CoV-2, the project will also inform efforts to control other diseases, while sustaining the position of the applicant and Switzerland as global leaders in infectious disease modelling research.",,2024,Department of Epidemiology and Public Health Swiss Tropical and Public Health Institute,871507.97,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Disease models | Disease transmission dynamics | Approaches to public health interventions",2021 +P28878,195658,DACH epidemiology conference,"Current events such as the outbreak of African swine fever or the rapid spread of the SARS-CoV-2 pandemic clearly show that animal diseases and zoonoses not only have very large biological impacts, but also enormous economic and social impacts. Human behavior and the motivation of those involved play a crucial role in preventing and combating diseases. For a holistic understanding of the connections, collaboration between epidemiology, medicine/veterinary medicine and social sciences is required. The conference offers an overview of the use of social-scientific methods in veterinary epidemiology. In doing so, it contributes to better networking between specialist areas and to more efficient promotion of human and animal health. For this conference we would like to invite five well-known scientists with whom scientific collaborations are also planned.",,2021,Veterinary Public Health Institute Vetsuisse-Fakultät Universität Bern,9726.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2021 +P28887,220961,"Clinical Nanomedicine 2023: Fulfilling the Global Potential Crossing the Horizon towards Novel Possibilities, Existing and Evolving Products, Technologies, Research and Strategies for Global Health","The nonprofit European Foundation for Clinical Nanomedicine will have after two virtual summits in 2020 & 2022 its 14th Summit as a hybrid event with personal attendance and live stream. CLINAM 14 /2023 will be the unique traditional platform with a scientific programme that will elucidate the state of the art of nanomedicine in production, development and the clinic for prevention, diagnosis and therapy. Since the development of mRNA vaccines based on lipid nanoparticles, nanomedicine has received huge awareness and has matured to a boosting field with highest recognition. This is the right moment to review the development of the technology as well as looking at the products and their use in clinical medicine at patient's bed. The achievement of the revolutionary protective wall against COVID-19 by mRNA vaccines predicts a profound acceleration of innovative drug development to the benefit of patients. However, not for all humankind: How can we enable and improve health care in countries where therapy until today is unaffordable or absent? For this, delivery of drugs by different nanoparticles shall be an important issue. All stakeholders in the field, including many high-ranking scientists, Nobel Laureates and leading managers and regulatory authorities from all continents exploit the CLINAM-summit since 15 years for new projects and making bonds for cooperation. All speakers contribute to an excellent scientific outlook. For 2023, CLINAM addressed three outstanding organizers of renowned conferences and invited them to participate with a session within the CLINAM Summit. The different skills of the parties will give a unique interdisciplinary perspective on nanomedicine and related fields in Europe and on the International level. The international Regulatory Authorities shall have their IPRP Meeting during the Summit. Format of the Meeting The Summit will take place on the Novartis Campus in Basel, which is since last year open to the public. The summit shall have on one day only plenary sessions and will take place in the auditorium, which is located in the impressive building designed by the architect Frank Gehry. The exhibition, poster presentations and lunches will be in the Foyer of the halls. The CLINAM Team will organize the meeting with as few as possible hurdles for the participants and is grateful for the support that Novartis gives by making the halls available to CLINAM. Target Audience The faculty includes pioneers and opinion leaders in medicine, nanoscience, and targeted medicine, physicians and scientists with a background in pharmacology, biology, physics, chemistry, biophysics, medicine, materials science, and engineering. Industry members find contacts for cooperation, get insight into the novel concepts and meet keen investigating startups, interested in working together. Developers from the pharmaceutical industry present their recent findings and research. The meeting is a particularly useful source of knowledge for the targeted medicine and delivery community. The conference is also of interest to members of the regulatory authorities as well as policymakers, all experts from industry in the field of life sciences, developers of new tools and materials for nanomedicine, and all those investigating the potential of emerging technologies in the field of healthcare and their combinations. Experts from venture companies can acquire knowledge on existing and upcoming developments and novel products in the establishing field of nanomedicine and knowledge-based medicine. Government authorities can profit from the international regulator's sessions. CLINAM is the worldwide melting pot for experts and a high-level communication platform where you meet those striving for nanomedical goals.",,2023,European Foundation for Clinical Nanomedicine,16959.93,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2023 +P28891,207955,"Philosophy of Infectious Disease Epidemiology: Modeling, Values, and Policy Advice","Attempts to control pandemic disease caused by a transmissible pathogen such as SARS-CoV-2 rely in part on elaborate epidemiological models. Even though there exists a large philosophical literature on scientific modeling, the specific epistemology of these epidemiological models is currently not sufficiently understood. Furthermore, there are many unsolved practical issues about how such models should inform policy. In particular, we are lacking an explicit understanding of what makes models adequate for policy purposes. Simply requiring that such models and their results be predictively accurate, valid or empirically confirmed does not do justice to the complexities of model evaluation. For prediction in the sense of forecasting is not the only, perhaps not even the main function of epidemiological models in policy advice. As scientists often emphasize, their modeling efforts produce scenarios that would obtain if certain assumptions were satisfied. While specific forecasts of infection incidence or mortality are usually not very accurate or sometimes even wide off the mark, this doesn't necessarily mean that the models used by epidemiologists are useless. For the computed scenarios - counterfactual in nature as they are - could still be useful for deciding between different policy options. A central aim of this project is to determine what makes epidemiological models of virus transmission adequate for policy purposes, and how their adequacy can be assessed. The main rationale of this investigation is to treat epidemiological modeling as a kind of counterfactual or what-if reasoning and to epistemologically investigate what makes such reasoning sound. What defines a realistic or credible counterfactual scenario in the first place? What role can traditional model selection criteria such as parsimony or robustness play in model evaluation? And finally, is there a role for non-epistemic values in model evaluation, as many leading philosophers of science today believe? Finding justified answers to these questions is the specific aim of Part I of the proposed project. In addition to these epistemological issues, there are also unresolved issues as to how the results of scientific modeling should inform public health policy. Under what conditions can a scientific result be considered as sufficiently reliable to serve as a basis for policy decisions that affect the lives of millions of people and that may have drastic effects on public health as well as on the economy? What kinds of precautions should scientists take when publicizing modeling results that are ridden with uncertainty? In general, how should discourse between scientists, policymakers and the general public be organized in order to secure democratic legitimation of government interventions? Such questions have been widely discussed, including by philosophers of science, in the context of climate modeling but much less so in relation to infectious disease epidemiology. Therefore, Part II of the project aims at providing normatively adequate answers to such questions.Expected results from Part I include the identification of criteria of adequacy for policy-relevant epidemiological models and modeling results, especially counterfactual scenarios. Part II will provide a normative account of the due organization of discourse between science, policymakers and the public. The impact on the field of philosophy of science is the advancement of the epistemology of scientific modeling especially of what-if scenarios, and of the normative grounds for scientific policy advice. The social relevance of the project lies in its contributing to a better understanding of how science should and should not inform public health policy for the control of dangerous infectious diseases in a democratic society.",,2026,Département de Philosophie Faculté des Lettres Université de Genève,739303.19,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions | Policy research and interventions,2022 +P28894,211879,"Osteological analyses on the Late Medieval plague cemetery Bern Klösterlistutz including sex and age estimation, palaeopathology and palaeodemography",This research project focuses on osteological analyses in the Late Medieval plague cemetery Bern Klösterlistutz and will be conducted by Dr. Inna Potekhina and Dr. Marcel Keller.,,2024,UniBE International Universität Bern,111481.15,Human Populations,Unspecified,Unspecified,Unspecified,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Clinical characterisation and management,,2023 +P28895,211996,Endless infectious diseases. The case of syphilis for thinking about prophylactic mobilization-demobilization (20th-21st centuries),"The first phase of health mobilization in the face of the COVID-19 pandemic consisted of old social hygiene measures, such as travel restrictions, disinfection, and health certificates. These procedures, which play on human behavior, have proven effective against other infectious diseases in the past. Then, in a very short time, concerted and coordinated biomedical research produced vaccines raising a double hope: the rapid supplantation of this restrictive and expensive social hygiene system by a pharmaco-technical shortcut solution, and ultimately victory on the disease. A longer-term look shows us that the discovery of a magic bullet and socio-health demobilization in the face of infectious disease often go hand in hand. Indeed, a vaccine or an antibiotic often leads to the desire to get rid of the constraints of social hygiene. What forms does social demobilization take following the implementation of a pharmaco-technical solution (vaccine, medication or effective medical device), and what effects does it produce? More generally, what should we remember from such demobilization given the general observation of the difficulty of eradicating many infectious diseases, such as syphilis, plague, tuberculosis, measles. Based on the exemplary case of syphilis, this contribution seeks to analyze the determinants, structures and effects of health demobilization at the time of emerging from the crisis of an infectious disease pandemic.",,2022,Institut Ethique Histoire Humanités - iEH2 Faculté de Médecine Université de Genève,11478.54,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P28899,209808,Role of Commensal Bacteria in Promoting Environmental Persistence & Transmission of Influenza A Virus,"Influenza virus is a respiratory pathogen of global importance with high economic and health-care burdens. This virus infects 10-20% of the population every year, causing an estimated one billion cases of disease, approximately 400,000 deaths, and an annual economic burden of billions of dollars. Though dwarfed by the COVID-19 pandemic over the last 2 years, influenza virus has continually circulated within the human population since the first recorded pandemic over a century ago. During this outbreak of 'Spanish Flu', influenza virus killed an estimated 50 million people, and recurrent clusters of human infection with avian influenza viruses (e.g. H5N1, H7N9) pose a real risk for a repeat pandemic scenario in coming years. The globalization of our world paired with ever-growing agricultural practices potentiates this risk for an influenza pandemic, which we remain under-equipped to deal with. Vaccines for influenza virus are available, however they fail to induce cross-reactive immunity and must be updated and re-administered every year to cover new variants. They are also insufficient to protect against emergent strains from zoonotic sources (e.g. avian influenza H5N1 and H7N9). As an alternative strategy to vaccines, health-care policies also aim to reduce the impacts of influenza by preventing virus transmission. However, an incomplete understanding of the complexity of transmission continues to hamper progress towards this goal. Upon exit from a host, influenza virus encounters an array of hostile conditions, including desiccation from an abrupt change in relative humidity, RH (from approximately 100% within the respiratory cavity down to 40-60% in most indoor environment) and a change in temperature. Unless the environment is incredibly humid, virus-containing aerosols will rapidly evaporate to approximately half their initial diameter, inadvertently increasing the concentrations of internal salts and other components by nearly an order of magnitude. This process also lowers the internal pH of the particle dramatically. Influenza virus is additionally affected by external factors of solar ultraviolet (UV) radiation, and other open air factors (e.g. ozone). Despite these stressors, infectious viruses are readily detected in exhaled aerosols from human patients. This indicates mechanisms of protection or virus persistence are at play. Respiratory matrices (e.g. mucin) are hypothesized to stabilize influenza virus against environmental inactivation, but this has not conclusively been shown and exact nature of this stabilization is only postulated. Furthermore, commensals of the respiratory niche pose another potential 'stabilizer' that have not comprehensively been examined. Binding interactions between enteric viruses and resident bacteria have been reported in the past, and are known to increase viral stability for a number of enteric viruses, especially against heat stress and other inactivating treatments. Despite substantial microbial diversity in the respiratory tract, there has been limited research into similar pathogen co-operations, particularly from the perspective of virus stability during airborne transmission. This project seeks to unravel the mechanisms of virus inactivation and persistence in this setting. Findings will improve our understanding of influenza spread and persistence outside the host, and knowledge gained may enable development of novel air treatments or therapeutics to limit virus persistence, collectively improving our capacity to control respiratory virus outbreaks in our future.",,2024,Environmental Engineering Institute (IIE) École polytechnique fédérale de Lausanne,232998.1,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P28925,203041,Conditional factors and effects of school development for achieving high quality education. A process and impact analysis from a comparative perspective,"In connection with the central research desiderata of school development research, the following questions will be examined within the framework of the research semester: a) Which school-internal and external school factors influence school development processes in individual schools and what is the relationship between these factors? b) What effects do specific school development processes and dimensions have on the development of professional learning environments and on the learning of students? I will examine these questions from a multi-level analytical perspective, taking into account the complex, nested structure of education systems, and from an international comparative perspective . In addition, these questions can also be examined in relation to how schools are dealing with the COVID-19 pandemic, so that this pandemic can be understood as an ideal case of 'school development occasion'. The focus is on two large, third-party funded research projects whose data can be evaluated. Several English-language articles will be prepared in renowned international peer-reviewed journals and, if possible, submitted during the research semester and contributions prepared for international conferences.",,2022,Institut für Erziehungswissenschaft Universität Zürich,28353.42,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P28927,219063,What is Public Trust in the Health System? - Insights into Health Data Use,"The book provides an in-depth and evidence-based explanation of what public trust in the health system is. To do so, the book focuses on the case study of health data use. The content of the book summarizes 10 years of my work and is relevant for students, government officials and health policy makers. 1.Introduction The introduction chapter will provide a first glimpse at the importance of the topic to catch the reader's interest. Further, the chapter provides a short history about my previous work that led to the book. This will help the reader to locate the book in the present field of research and to relate to the book's angle (health policy, governance, and social science) on public trust. By knowing the background to the book, the reader will be able to better follow the arguments made and to use the information provided for his/her own work. Last, the introduction will provide an overview of the following chapters. Part 1: Why do we care about public trust in the health system? The first part has two main purposes:a)to introduce the reader to some basic concepts of trust to prepare his/her mindset for the following chapters, andb)to make the case for the importance of public trust.The second chapter provides an overview of the basic principles of trust which are for example, trust is a relational construct, trust is future oriented, the trusting party chooses freely to trust the trusted party, the trustworthiness of the to be trusted party is always assessed by the party placing trust. The chapter will further engage with health policy that aims to increase public trust such as policy fostering for example transparency and accountability, regulation, or ethical cultures. Building on previous theoretical work by Niklas Luhmann, Anthony Giddens, and Piotr Sztompka, this chapter will help the reader to develop a deeper understanding of what trust itself is and how public trust is different from individual and interpersonal trust. The third chapter will introduce the reader to three examples where public trust is important for the success of these health system activities. Adherence to COVID-19 measures, vaccination hesitancy and public support of health data use within the health system are the main examples to introduce the reader to public trust. All three examples are at present in the media and are therefore easily accessible to the reader if not personally relatable. Moreover, a large body of literature exists about the case studies, so that readers can dive deeper into the issues presented in the third chapter. Part 2: What is public trust in the health system? The second part has two main purposes: a)to explain how and where public trust develops, and b)to explain what public trust in the health system is. Chapter four will explain how public trust develops in the public sphere by public discourses between health system actors and citizens. Within the public sphere, private individuals and different actors from within and outside the healthcare system come together to discuss issues of trust based on their own experience or experiences of others. Examples of modern public spheres are, next to sports clubs and other social gatherings, online public spheres such as Twitter, Facebook, blog web-pages or even to some extend communities facilitated by different Mobile Apps such as Clubhouse, Instagram, TikTok and others. Despite the permanent communication noise on these platforms, discussions of public trust seem to develop around topical issues, e.g. vaccination or tracing apps. Discussion spheres calm down after the issue is resolved or morph into a new discussion sphere. Following an introduction on how and where public trust develops, chapter five, six and seven will guide the reader to the core of the book, the conceptual framework of public trust in the health system. I developed the framework during my PhD with empirical work in England using the three case studies: care.data, biobank research, and the 100.000 Genomes Project . Since then, I refined it and currently use it in my research project on public trust in electronic health records. Chapter five will describe the themes that cause public trust (e.g. Anonymity, Privacy, Transparency or Time). Chapter six will describe what the effects (Legitimisation and Participation) of public trust are, and chapter seven will explain how public trust is framed by issues (e.g. Zeitgeist, Religion, Fear, or Risk) that influence public trust but do not directly cause public trust. This comprehensive view on public trust will help the reader to not only precisely understand what makes public trust and what the effects are, but also to understand what issues frame public trust and therefore can have an impact on public trust. Chapter seven is particularly interesting for policy makers as it will focus on issues that are at times neglected in trust in health systems literature, such as human error, public mood, people's worldview. Part 3: How can we foster public trust in the health system? The final part of the book has three main purposes:a)to explain what governance and policy action can foster public trust, b)to emphasise the importance of communication and information for public trust building, and c)to explain what ways are suitable to quantify public trust. Within this forward-looking part three, chapter eight will introduce the reader to eight policy recommendations that can increase public trust. The recommendations are: Do not rush trust building; Engage with the public; Keep the public safe; Offer autonomy to the public; Plan for diverse trust relationships; Recognise that emotions and calculated decisions influence trust; Represent the public interest; and, Work towards a net-benefit for the health system and the public. The recommendations directly link to the conceptual framework presented in part two and are therefore relatable at this stage in the book. By using first results of my current work on the implementation of the conceptual framework of public trust into practice, I intend to provide additional real-world examples on how these recommendations can be applied into practice. As information exchange is critical for public trust establishment chapter nine explains the importance of communication, signs and signals. Without exchange of information in one form or the other, it is not possible to build public trust. Therefore, communication is central to the public trust building process. Next to conversation or one-way media communication, a particularly interesting, but at times forgotten form of communication are signs and signals. Might it be a reputable label, such as the blue NHS England label or the body language of a spokesperson, very recognizable and visible but also subtle cues and hints can contribute to the build-up of public trust. Chapter ten will introduce the reader to quantification of public trust. Quantification in terms of measurement or polling is common practice in public trust research and politics. Eventually, public trust can serve as a performance indicator or outcome measure. Yet, the concept of public trust introduces challenges to these methods and therefore they need to be conducted with care to deliver a meaningful result to health system actors and the public. Alternatives to measurement will be discussed as for example counting effects that are seemingly related to trust such as vaccination uptake or observation of public discourse with digital methods as an alternative altogether. 11.Conclusion The last chapter will highlight the main points made in the book.",,2023,CYREN ZH UZH Digital Society Initiative University of Zurich,9398.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2023 +P28928,198336,Risk Perception and Tourism Behaviour: How to Control Pandemic Infectious Diseases Through Non-Pharmaceutical Interventions (NPIs) ?,"Starting point: Transport networks can be understood as vectors in the distribution of pathogens. Tourism in general is one reason for COVID-19 jumping regional boundaries to infect humans. Thus, international outbound and domestic tourism by the Swiss population for purposes of business, recreation and visiting friends and relatives (VFR) is one source of infection of COVID-19 and marks out viral transmission routes due to exposure to and social interactions with other tourists and locals at tourist destinations. In 2018 there were 55.4 million overnight stays in tourist accommodation by Swiss residents. Research Question:How do travelers perceive the risk of pandemic infections while traveling and how does this affect decisions regarding tourist behavior and the usage and acceptance of non-pharmaceutical interventions (NPIs) while travelling? Answers on this research question is essential for breakthrough research in containment measures. Objective: This research will set the groundwork for evidence-based intervention design in the domain of tourism behaviour in order to control pandemic infectious diseases by non-pharmaceutical interventions (NPIs).Method: Socio-psychological models are promising new approaches in Covid-19 research on epidemiology and disease prevention. We combine the well-established Theory of Planned Behaviour TPB with the Health Belief Model HBM to the scope of the application of tourism based on a nationwide representative survey. By identifying significant influencing dimensions from the combination of these two models, various measures and interventions will be researched by means of a second surveys that is based on an experimental design. Practical Implementation: By means of evidence-based intervention designs, the intended project results will develop new strategies and guidelines for infection prevention and population monitoring in the high-risk field of tourism. These strategies and guidelines for infection prevention in the field of tourism will lead to toolboxes (brochures) guiding containment measures to be used by our stakeholders, which include - inter alia - the Swiss Federal Office for Civil Protection FOCP.",,2023,Institut Tourismuswirtschaft (ITW) Hochschule Luzern,423282.99,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Policies for public health, disease control & community resilience",Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions | Communication,2020 +P28934,221399,The Emerging Regime Complex for Pathogen Genetic Sequence Data (GSD) Sharing Platform Infrastructure,"The COVID-19 pandemic has demonstrated the crucial role of rapid and reliable international pathogen genetic sequence data (GSD) sharing in global genomic surveillance and development of medical countermeasures (WHO, 2022a; IHR Review Committee, 2023). Such sharing occurs on specialized digital platforms, such as GenBank and GISAID, subject to platform policies and the scientific principle of open science. However, the rules governing pathogen GSD sharing are soon likely to change, as the topic has attracted increased attention from policymakers and has been included as part of the ongoing international regulatory processes. The amendment of the International Health Regulations (IHR), negotiation of a new pandemic instrument, publication of the WHO guiding principles for pathogen genome data sharing, as well as the recent decision to include GSD as part of Kunming-Montreal Global Diversity Framework and the proposal to establish European Health Data Space (EHDS) may all contribute to the establishment of a regime complex for pathogen GSD sharing, affect the pathogen GSD sharing platforms and, thus, have impact on the way we prepare for and respond to future pandemics. Research questions: What are the policies and principles which currently govern pathogen GSD sharing through GenBank and GISAID? Based on the outcomes of the ongoing international regulatory processes, what are the new rules of the emerging international regime complex for pathogen GSD sharing? How will the new international rules affect the pathogen GSD sharing digital platforms? How has the infrastructural aspect of GSD sharing platforms featured in platform policies and in the international regulatory processes? Method: The collection of data will be done by 1) desk research of platform policies currently governing pathogen GSD sharing; 2) participation in webcasted meetings and 3) gathering of policy documents and reports from international organizations (IOs), governments and non-state actors concerning international regulatory processes for GSD; 4) 25-30 semi-structured interviews with: informants from pathogen GSD sharing platforms, database managers, staff at public and academic laboratories and experts from IOs; and 6) analysis of the collected data through the lens of academic literature on regime complexity and infrastructural approaches to platform regulation.Novelty: This project constitutes the first academic study which maps the emerging regime complex for pathogen GSD sharing while treating platforms in this space as infrastructures. It proposes to track the ongoing progress in international regulatory and legislative reform processes and negotiations, where new data is expected to be generated in real-time. Furthermore, the project envisages a novel conceptual contribution to the literature on regime complexity and infrastructural approaches to platform regulation by applying insights from scholarship to a new and emergent field of regulation. Finally, this research project seeks to address the empirical question of how ongoing regulatory processes in international law affect the GSD sharing platforms and, thus, study the impact of new international legal rules on digital platforms in the context of pathogen GSD sharing. Expected outcomes and impact: Two academic articles in leading international law journals, the first article mapping out the emerging international regime complex for pathogen GSD sharing and the second article building upon the empirical data to outline the impact of new international rules on pathogen GSD sharing platforms understood as infrastructures of global pandemic preparedness and response (PPR). The research aims to contribute to the scholarship on regime complexity and infrastructural approaches to platform regulation with insights generated by application of concepts from the literature to an emerging international regime for pathogen GSD sharing. It also aims to be of use to practitioners in the field who are interested in navigating the emerging international regime complex.",,2025,Governing Pandemics Team Global Health Centre Geneva Graduate Institute,110490.59,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Policies for public health, disease control & community resilience",Policy research and interventions,2024 +P28946,198253,Rapid Hybrid Structure Determination of Coronavirus Protein-RNA Complexes as a Basis for Drug Screening for the Treatment of COVID-19,"The ongoing pandemic caused by SARS-CoV-2 calls for world-wide, concerted efforts to generate new insights into the biology of betacoronaviruses. Because coronaviruses are single-stranded RNA viruses with a large (approximately 30 kilobases) RNA, the interactions between viral proteins and the viral RNA are of central importance to essential functions of the virus, for example replication in the host cell. Surprisingly, very little is known about the details of these interactions at a molecular level as high-resolution structures of protein-RNA complexes of SARS-CoV-1 and 2 or MERS-CoV are completely absent. Insights into the three-dimensional organization of the interplay between protein and RNA which are highly conserved in this virus family would however enable the development of new therapeutic approaches, also in preparation for the likely re-emergence of a related virus.To fill this gap, we propose to perform structural studies on two very important RNA-binding proteins of SARS-CoV, the nucleocapsid N protein and the non-structural protein 3 (Nsp3), by characterizing their interactions with RNA which will be the basis for performing rational drug screens. To achieve this, we will combine the expertise of the two applicant groups in the structural analysis of ribonucleoproteins: Nuclear magnetic resonance (NMR) spectroscopy and protein-RNA cross-linking coupled to mass spectrometry (MS). In a stepwise fashion, we plan to apply these techniques individually, starting with individual domains of the target proteins from both SARS-CoV-1 and 2. Results from these complementary methods will then be combined in an integrative approach to obtain structural insights of their mode of binding to RNA. Also complexes between full-length proteins and RNA will be investigated. With the availability of structural data of two viruses, commonalities and differences between them will allow the generation of new hypotheses related to their pathogenesis and provide the basis for new therapeutic approaches. We will take advantage of these information to perform drug screening, adding an element of immediate translational impact to our structural biology efforts. The combination of NMR- and MS-based approaches is known to accelerate structure determination of challenging targets, which is of particular urgency in the context of the current and future global health threat by this group of RNA viruses.",,2023,Insitut für Biochemie ETH Zurich,790042.6,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Diagnostics | Pre-clinical studies,2020 +P28947,215555,Structural and phase-separation investigations of the hnRNPs and viral RNPs,"RNA is a very versatile molecule as it is in essence single stranded having the possibility to fold into itself or bind proteins. While DNA compaction is fairly well understood and structurally characterized at atomic level, RNA compaction is much less understood possibly due to the dynamic nature of RNA as it can exchange between multiple conformation and be bound by thousands RNA binding proteins (RBPs). Yet, RNA does compact as seen with viral RNA encapsulated in viral capsid or as part of pre-mRNA particle like the 40S ribonucleosomes. Studying RNA packaging faces an other obstacle in the fact that RNA alone and RNA-protein complexes tend to phase-separate at physiological conditions (concentration and buffer conditions), rendering studies of RNA compaction by RNA binding proteins very difficult to do. We postulate here that RNA compaction by RBPs requires a phase-separation step in order to concentrate and compact the RNA. This phase-separation step is then followed by a maturation step allowing the ribonucleoparticles to reach a stable conformation. As model systems, we are studying the 40S ribonucleosome which is a particle postulated to compact introns in human cells and the SARS-CoV2 Nucleocapsid (Nu) which is postulated to compact the viral RNA genome into its capsid during virion formation. We recently rediscovered the existence of the 40S ribonucleosome which has been postulated in the 60-70s to be the compacting unit of pre-mRNA. We also found out that region of the proteins important for ribonucleosome formation are also crucial for liquid-liquid phase separation (LLPS). We therefore aim at understanding the LLPS properties of the major components of the ribonucleosome (namely the protein hnRNPC1/2, hnRNPA1/2, hnRNPB1/2 with and without RNA), how the droplet mature over time and ultimately how they fold into a 40S compacted particle. Similarly, we aim at understanding the LLPS properties of the SARS-Cov2 Nu that phase separates in the presence of RNA but also of cognate proteins and nucleotides. Nu phase separation is critical for the viral gene expression and its encapsidation. We therefore will study droplet formation of Nu with RNA and various binding partners, follow the maturation of the droplets and observe if the droplet can mature into folded ribonucleoparticles.",,2027,Insitut für Biochemie ETH Zurich,818202.53,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P28949,196256,NMR studies of SARS-CoV-2 accessory proteins,"Form and function are one, and deciphering structure provides the fundamentals to interfere with function, as central in the context of infection. We here propose to reveal the structures of a group of proteins which the SARS-CoV-2 virus, causing the current pandemic, carries on a non-essential basis, hence their name: accessory proteins. We concentrate on these proteins for two reasons. First, and most importantly, a significant body of evidence has accumulated that points an accusing finger to the accessory proteins and their contribution to viral fitness through modulating the host response to virus infection. Them being the most varying elements in coronaviruses supports this role, since SARS-CoV-2 carries accessory proteins not observed in other human viruses before. Second, the large majority of accessory proteins are small, and often membrane-interacting. NMR is here the method of choice, and notably solid-state NMR. We will combine NMR with cell-free synthesis of the protein samples, an approach which has the central advantages of producing even complex proteins often in well-folded form, and to allow for fast screening of candidate proteins and conditions. Analysis of the samples is enabled by highest magnetic fields and most recent NMR methodology allowing to analyze as few as 100 micrograms of protein, compatible with the quantities obtained from cell-free synthesis. The two PIs on this proposal have a long-standing collaboration (85 common papers), and are strongly committed since several years to this new approach, particularly also through A. Böckmann being a guest scientist at ETH (2020-2023). They plan to apply it here to SARS-CoV-2 accessory proteins to contribute in the fight against this emerging pathogen.",,2023,Laboratorium für Physikalische Chemie D-CHAB ETH Zürich,499753.78,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Innovation,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P28951,205323,"SARS-CoV-2: understanding the entry, multi-organ spread, and immune response in the context of vaccination and re-infection","Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) with fatal acute respiratory disease has rapidly spread worldwide. Our knowledge about SARS-CoV-2 is accumulating, but its spread to the entire organisms with deleterious consequences and the immunology responses to virus, vaccination and treatment in the context of reinfections are still scarcely understood. The main goal of the project is to characterize the so far elusive biology of entry and pathological organ-specific consequences of SARS-Cov-2 and its variants via ACE2, Neuropilin 1 and Transferrin receptors and the development of the immune response, including the possibility that antibodies, elicited by natural response to infection, vaccination or immunotherapy, could generate serious adverse effects through Antibody Dependent Enhancement (ADE). This project is based on our successful pre-work, established technologies, and on our recent joint publication designing and characterizing novel anti-SARS-Cov-2 therapeutic antibodies (De Gasparo et al., Nature, 2021).",,2025,Institute for Research in Biomedicine (IRB) Università della Svizzera italiana,641127.23,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Characterisation of vaccine-induced immunity",2022 +P28952,215559,Multispecific antibodies against infectious diseases,"Antibody therapy is safe and effective against infectious diseases. It is complementary to vaccines and mostly needed by people that cannot or do not want to be vaccinated, cannot mount an adequate response (e.g. immunosuppressed) or have waning protection over time. Antibodies can be used therapeutically after symptoms appear, being immediately effective, or they can protect prophylactically pre- or post-exposure.SARS-CoV-2 has shown both the power of antibodies, which were approved even before vaccines and have been a life saver for many, and their weakness, because early adoption was lacking and because all approved antibodies were rendered ineffective by emerging variants. Research to overcome these limitations is warranted.Resistance to viral mutations can be achieved by targeting highly conserved, potently neutralizing regions that are critical for viral function and thus not easily altered by the pathogen, such as the fusion peptide. However, fusion peptides are usually inaccessible on the viral surface and exposed only through structural rearrangements during the molecular infection process.Here we aim to design novel, multispecific antibodies capable of reaching potently neutralizing, conserved, but normally inaccessible epitopes. The idea is to anchor one half of a bispecific antibody to conserved, accessible but not neutralizing epitopes. The other half targets the fusion peptide or similar. It remains free on the viral surface outside the cells, but it is ideally located to immediately bind the fusion peptide when it is exposed after cleavage or endocytosis.We will engineer and extensively characterize such multispecific antibodies against the SARS-CoV-2 Spike, fully expecting to be able to neutralize viruses as distant as MERS. To prove the power and versatility of the approach, and for risk diversification, we will also design similar multispecifics against the flavivirus E-protein.Adoption of antibody therapy is hampered by uncomfortable and logistically complicated administration routes, often intravenous; and cost, particularly relevant for middle- and low-income countries where infectious diseases often have larger impact. mRNA delivery, which received a huge boost from the SARS-CoV-2 vaccines success, has the potential to solve such problems. A simple jab of micrograms of mRNA can stimulate production of the equivalent of grams of antibodies in the patient. However, current mRNA technology does not allow delivery of multispecifics or antibody cocktails, which are required for the above approach and more generally to resist to and prevent formation of viral escape mutations. Simultaneous mRNA delivery of two or more antibodies has practical and regulatory hurdles.A second goal of this proposal is to establish a robust mRNA system for delivery of novel bispecific antibody constructs engineered for optimal production through mRNA delivery, overcoming the chain shuffling and uncertain stoichiometry of currently available technology. We will verify their production yield, stability, biophysical and molecular properties, ability to neutralize the virus and protect from infection in-vitro and in-vivo. The characteristics of mRNA delivered antibodies will be compared to those of the same constructs produced with traditional methods. This interdisciplinary project covers antibody and mRNA engineering, cellular and biophysical assays, immunotherapy, physiology and immunotherapy for infectious diseases. It has the potential for high impact scientific publications and excellent training opportunities for PhD students and Postdocs. We already have reagents, assays, expertise and international collaborations ensuring prompt and effective project progression.",,2027,Institute for Research in Biomedicine (IRB) Università della Svizzera italiana,847996.65,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Zika virus disease,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P28953,221503,Immunotherapy for Infectious disease (ITID) conference 2023,"The ""Immunotherapy for Infectious Diseases Conference"" brings together academia, small biotech, pharma and regulatory bodies invested in the discovery of novel therapeutic strategies. Infectious diseases remain a leading cause of morbidity and mortality worldwide, necessitating novel and innovative therapeutics. COVID-19 demonstrated the importance of networking and scientific exchange between scientists, researchers, medical doctors, private companies and regulatory agencies to move rapidly and effectively. COVID-19 also showed the high positive impact of antibody-based immunotherapy, which was particularly safe and effective, literally saving thousands of lives.Our conference covers all aspects of immunotherapy for infectious diseases including academic, clinical, biotech start-up, pharma and regulatory aspects. Current and future challenges in infectious diseases range from neglected diseases affecting the poorest countries to antimicrobial resistant pathogens in modern hospitals; from rare but deadly infections affecting few, to the threat of potential global pandemics; from pathogens reaching new geographical areas due to climate changes to disease reemerging due to lack of vaccination coverage. The ability of the human immune system to fight pathogens can be exploited for effective therapeutic strategies. Recombinant and further engineered antibodies can be used as active ingredients, as targeting agents to selectively deliver drugs or to establish novel vaccination strategies. Bringing a novel therapy to the patients requires the combined effort of several players, all of which are brought together in the ""Immunotherapy for Infectious Diseases Conference"", with world high caliber speakers and participants. The congress is organized in the USA and Europe in alternating years with the aim to serve as a forum to exchange ideas and foster cross-disciplinary collaborations.The main question addressed by the conference: what is the state-of-the-art in infectious diseases, and how can we push it forward?",,2023,Institute for Research in Biomedicine (IRB) Università della Svizzera italiana,17488.47,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,,,2023 +P28959,210193,Learning from the Impact of Covid-19 on Educational Practice to Expedite Pedagogically Meaningful Digitization,"In January 2020, the World Health Organization (WHO) reported the first infections with the Covid-19 virus in Europe. To control the infections, schools in Switzerland were closed nationwide. As a result, students were in distance education for eight weeks. Studies on the impact of school closures expressed certain fears but also hopes. Fears were expressed that students were experiencing more stress and mental health problems were more prevalent. Some studies on lockdown effects described also fears of stagnation, a decrease in student performance or a lower level of competence acquisition than in school years under normal conditions. This could also have a negative impact on society as a whole. Besides serious consequences for the individuals (e.g., lower chances in the labor market and lower future income), we assume that the pandemic has an impact on students' well-being and the perceived future prospects. Hopes were, in particular, that a more temporally flexible and individualized design of learning, a more undisturbed working environment for some students at home, the promotion of self-regulated and autonomous learning as well as an accelerated digitalization of schools would become possible. The available evidence on learning losses is characterized by a high degree of heterogeneity, and there are only few reliable findings for Switzerland. Consequently, it is difficult to draw conclusions about the Swiss situation from international data. To obtain evidence on this, we address the following research question (RQ 1): To what extent did learning losses show up at the time of school closures in Switzerland? The school closures have shifted the significance of digital tools to a new level. The role of such tools changed from an add-on to traditional schooling to a necessity in avoiding an entire educational shutdown. Switzerland is in the extraordinary position of supporting compulsory schools with digital learning support systems that allow to assess student competencies, offer feedback on students' learning progress and provide individualized learning tasks. To date, however, it remains unclear (a) how exactly teachers and students have used digital learning tools during the pandemic, (b) to what extent the factors relevant to distance learning influenced and interacted with the use of digital tools, (c) what their potential is for supporting learning in mandatory distance learning and (d) how the tools themselves might be further developed to support effective learning in comparable challenging situations. To obtain in-depth insights of both scientific and practical relevance, our project aims to address the following RQs: (RQ 2) What impact did school closures have on teachers' and students' use of digital learning support systems? (RQ 3) What relationships exist between the use of digital learning support systems by teachers and students and the (compensation of) learning losses? (RQ 4) Are learning losses, the use of digital learning support systems, and the relationships between learning losses and use of these systems moderated by school context (e.g., SES composition) and school type? (RQ 5) Which individual student characteristics are relevant to learning losses in distance education, and how are they related to the impact of learning support systems on these learning losses? (RQ 6) Which further developments with respect to learning support systems and their implementation into instruction are needed to better prepare for future pandemics (or comparable situations of distress) and to expedite pedagogically meaningful digitization? (RQ 7) How can the theoretical model of distance education proposed by Helm, Huber and Loisinger (2021) be further developed to reflect the role of digital technologies more precisely in distance education based on the experiences from the school closures?The digital learning support systems at the heart of the proposed project are Lernlupe and Lernpass plus, systems for primary school (3th to 6th grade) and lower secondary school (7th to 9th grade). We will realize two quantitative studies based on secondary analyses of Lernlupe and Lernpass plus datasets. First, longitudinal analyses with competence test data from the years 2019 to 2021 will be conducted. Second, changes in the use of tests and learning sessions available in the systems will be examined and related to students' competence development. By including school context and school type variables, variation in the use of the tests/training sessions and their relationship to test results will be analyzed (e.g., to investigate potential benefits of digital learning support systems for students from lower-proficiency school types). Moreover, a qualitative study based on teacher interviews and document analyses will be conducted. The interviews cover the following topics: Learning losses during school closure; usage of digital learning support systems before, during, and after school closure as well as implementation in distance learning; preconditions on the side of the teachers and preconditions on the side of the students. Additionally, we will analyze any documents provided by teachers that were used in classrooms or at school level which might give insights into how the systems were applied throughout the pandemic. Finally, we will analyze data from the study ""Mein Coronatagebuch"" (""My Corona diary""). In this study, among others, students were asked what worked well for them in distance learning and what difficulties distance learning had presented to them. As part of the proposed project, these questions will be evaluated using qualitative content analysis.Based on the empirical findings, a usage model will be developed that provides guidelines for the use and didactic implementation of digital learning support systems in distance education. To ensure that this usage model fulfills the requirements of practice, it will be developed together with the relevant stakeholders in practice (teachers, school principals, educational administrators, experts in digitization). Also with representatives of the practice we aim to further work out an existing theoretical model for distance learning with special attention to digital technologies. To establish the link to practice, partner schools are recruited and we have set up an advisory board with stakeholders from different levels. The board is chaired by Prof. Dr. Stephan Huber, who has broad experience in the field of cooperation with various practical actors.Taken together, the project will deliver results on three levels: (1) We will produce scientific insights, which will be disseminated through the main scientific channels, informing the scientific community, educational administration, and policy makers. Reliance mainly on existing datasets and secondary analyses ensures that these insights can be gained on a short time scale. (2) We will dedicate substantial dissemination activities to inform practitioners to enable a swift take up of research findings. Thus, in order to disseminate the usage model, Open Educational Resources will be developed together with teachers, explaining how to implement the model. In addition, workshops will be held for teachers, school principals and other interested persons. In educational forums, the usage model as well as the theoretical framework model will be discussed with stakeholders from the field. (3) We will address technology providers by delivering a conceptual blueprint, informing the further development of digital Swiss learning support systems as well as the future advancement of educational technologies more generally. As a whole, by advancing a pedagogically meaningful digitization in education, the proposed project will contribute substantially to mitigate the feared negative individual and societal impacts resulting from pandemics and similar states of emergency.",,2026,Institut Kompetenzdiagnostik Pädagogische Hochschule St. Gallen,308742.67,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P28963,210123,Harnessing the potential of data visualization and narratives produced by media and public actors in times of pandemic or health crisis,"How well the public understands data has a major influence on the successful management of pandemics and other health crises. Data related to Covid-19 has been extremely abundant but not always well understood by citizens, sometimes resulting in confusion and/or resistance to public health measures. Improving how well data is understood is therefore critical from a public health perspective, and to the proper functioning of our democracies more generally. These are the premises on which the present project is based. Its aim is therefore to contribute to a better understanding of data in future, which can be achieved by improving data literacy (reception side) and by presenting and explaining data in ways that facilitate its understanding (production side). However, achieving higher levels of data literacy within the population - while desirable - cannot be achieved overnight. Identifying news media as playing a central role, this research project seeks to find ways of helping news media and other information producers/disseminators to improve their practices related to health crisis data, including thanks to a better understanding of audiences.In this project data is viewed through a social constructionist lens, in that it may not be assumed to exist in a raw or pure state and is not, as such, neutral. They are the result of - and subject to - the operations of sense making carried out by various actors (including journalists) with a view to informing the public. Data are therefore inseparable from their meaning and narration (whether textual, visual, interactive, etc.). By extension, data should not only be understood from the point of view of their construction, production and even circulation, but understanding the reception side is both paramount and frequently overlooked.Public reception, which we argue tends to be viewed as monolithic, remains a blind spot for data producers as well as for research more widely. Academia has focused much more on the creation side of data than it has on the ways in which they are then understood and interpreted variably by different audiences. The data boom during the Covid-19 crisis has exacerbated a growing phenomenon: the dissemination of erroneous information. As data's importance in understanding the world and decision making has grown, they have increasingly become subject to distortion and manipulation from their original meaning in order to propagate false information (e.g. disinformation or statactivism) and more often for misinformation (unintentional misinterpretation), usually due to a variety of factors such as the lack of quality of the data, of expertise by news providers or of data literacy on the audience side.On a methodological and theoretical level, this project will explore the production, dissemination and reception of data in the form of news during the pandemic, in line with systemic approaches widely used by researchers in journalism studies in recent years. It is based on a collaboration of a multidisciplinary team of researchers (journalism studies, consumer behavior, visual science and information systems) and the participation of professionals and institutions (news media, journalism training, public health institution and the Federal Statistical Office).More concretely, our research will explore how trust in media, levels of data literacy and preexisting beliefs shape how members of the public understand and make sense of data.The project is divided into five work packages:+ WP1 aims to identify the key indicators and data produced by journalists during the COVID-19 pandemic in Switzerland as well as the evolving ways in which this data framed the health crisis.+ WP2 will conduct qualitative case studies in view of documenting data journalistic approaches to COVID-19 data-related narratives. In particular, which representations journalists have of the data and their audiences, and how they shaped their stories to make the two fit.+ WP3 will use the knowledge gained in WP1 to conduct controlled experiments to gain a better understanding of audience comprehension of data-related narratives, seeking ways to reduce misunderstandings and skepticism.+ WP 4 will adopt a collaborative design science approach to create digital data-related narratives and visualizations and test them to evaluate how well they support data understanding. It will build on the observations made with journalists in WP2. Broadly, it will consider how interactive data visualizations with adequate narrative strategies could empower the audience of data-related narratives. + Finally, WP5 will disseminate the knowledge gained and technologies developed, notably thanks to broad-ranging partnerships, including the news media, public health authorities, journalism training institutions.In terms of impact, this project will thus improve data-related narratives to promote better information in times of pandemic, accounting for the conditions of reception and understanding by the public and by promoting more interactive and inclusive narratives, thereby offering contributions on societal, industrial and pedagogical levels.",,2026,Académie du journalisme et des médias Université de Neuchâtel,545453.08,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Switzerland,,"Health Systems Research | Policies for public health, disease control & community resilience",Health information systems | Communication,2023 +P28967,211225,"Evolution, persistence, and spread of endemic viruses","There is a huge diversity of human endemic viruses - and most of us are infected by many of them each year - yet so much of our research focuses on only a few 'headline' pathogens. Though our deeper understanding of viruses like HIV and influenza has been critical to combatting them, it only scratches the surface of a broader understanding of how human viruses evolve and the interplay with human immunity. As the pandemic has highlighted, our ability to understand, anticipate, and respond to new viral threats is limited by what we've previously discovered in other viruses. With high-throughput sequencing and characterization of SARS-CoV-2 now common place, I believe we have an unprecedented opportunity to gain a much more comprehensive understanding of viral diversity and variation by embarking on a comprehensive, phylogenetic approach to study endemic human viruses.Focusing on the Enterovirus family, with Enterovirus D68 (EV-D68) as my starting point, I aim to exploit both publicly available sequence and serological data to explore (i) phylogeography: the seasonal patterns and geographic connections between outbreaks; (ii) genetic bottlenecks and diversity: how lineages diversify and persist between outbreaks; and (iii) antigenic evolution: how immunity is shaped by initial and subsequent exposures and whether viruses evolve to evade this immunity.Aim 1: Create phylogenetic analyses, starting with EV-D68 but expanding to other non-polio Enteroviruses (NP-EVs), to explore geographic connections, antigenic evolution, and genetic diversity. By including available demographic information, I can describe the geographical spread and mixing both within and between outbreaks and the patterns observed in countries exchanging viruses, as well as investigate associations with clinical data. Additionally, the COVID-19 pandemic created an unprecedented reduction in viral respiratory viruses, resulting in a unique opportunity to study persistence, genetic bottlenecks, and characteristics of successful lineages.Aim 2: In this collaborative aim, I will investigate the role of antigenic evolution and the contribution of asymptomatic infection to circulation and persistence. We will measure titres of multiple serum samples against a panel of antigens and integrate them with viral phylogenies in time and space. I will infer the likely exposure profiles for individuals of different ages from different places and construct an optimal set of antigen samples that span viral diversity. Using cross-sectional and longitudinal sera, I will quantify cross-reactivity across clades and time (looking for signs of 'original antigenic sin'), and investigate the impact of reinfection. Aim 3: Integrate epidemiological, phylodynamic, and serological data into models to explore hypotheses about transmission and immunity. Using models that incorporate naïve children, variable immunity in adults, and travel data prior to and during outbreak periods, I can explore what parameters allow us to replicate the periodic outbreaks observed in children, whether adults serve as a reservoir between outbreaks, and how variants mix during and between outbreaks regionally and globally.Through metagenomics, we are gaining an ever more detailed descriptive picture of what viruses live with us; my aim is to complement these efforts through a comprehensive understanding of how these individual virus species spread and change. Through phylogenetic and serological study of Enteroviruses, we can better comprehend the long-standing interplay of human immunity and the evolution of the endemic viruses that we encounter throughout our lives. In my proposed project, I will start to create the framework for exploring the evolution, dynamics, and transmission of the common endemic viruses that we live with every day.",,2028,Medical parasitology and infection biology Swiss Tropical and Public Health Institute University of Basel,1996818.39,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen | Other,,,,,,,,,Disease X | Other,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2023 +P28971,210229,COV-19-DILEMMA: Between Protection Benefit and Social Harm. Impact of Non-Pharmaceutical Protective Measures in Nursing Homes,"At the onset of the COVID-19 pandemic, health authorities and the medical community focused on hospitals and intensive care units because of the severe course of infection in a significant proportion of patients. At the same time, a tragedy of an even greater magnitude unfolded elsewhere: The over proportional number of deaths of older people. Non-pharmaceutical interventions (NPIs) such as physical distancing, movement restrictions or social isolation were applied to protect the lives of the residents, who were quickly identified as most vulnerable to health deterioration. While NPIs can be powerful tools for pandemic controls, they can also have harmful direct and indirect effects. The proposed study will investigate this dilemma of harms and benefits of NPIs in nursing homes during the current COVID-19 pandemic. The overall objective of this study is to gain a comprehensive understanding of NPIs, e.g. social isolation practices and their impacts on residents and their families. Of particular interest are the underlying mechanisms and the consequences of NPIs to best inform future public health policy, and nursing home responsibles in addressing the threats of the pandemic for vulnerable populations. Nursing home responsibles are in a (ethical) dilemma and may benefit from policies to support their decision-making on the stringency of isolation measures, facing their positive and negative impact. An exploratory mixed-methods research design will be applied to tackle this aim:1) A full census online survey will be distributed among all nursing homes in Switzerland. Nursing home responsibles will be asked about the facility size, the region (urban vs. rural), state or private responsibility, as well as epidemiological information regarding COVID-19 outbreaks, duration, manner, and specific forms of conducted NPIs. The survey questions will be informed by pandemic response recommendations suggested in the literature. Furthermore, we will collect pandemic preparedness of the nursing homes using an adapted version of the COVID-19 preparedness survey. The information about the conducted NPIs will be used to calculate an index indicating the strictness of conducted NPIs. 2) Based on the NPI index (ranging from loose to very strict NPIs) and different national regions selected nursing homes will be invited to participate in the second study part (purposive sampling). Within this study part we will explore perceptions, experiences and consequences of the implemented NPIs in focus groups with the nursing staff, responsibles and primary care physicians (PCPs). The overall aim of the focus groups is to gain an in-depth understanding of the conducted NPIs, the reasons for the decisions reached, the harms and benefits caused by the measures, concrete suggestions for improvement and potential lessons learned. In addition step 2) will include, a mixed methods study among the residents and their next of kin will be conducted in this study part. For the mixed methods study, qualitative partially structured interviews among residents and their next of kin will be conducted. The topics will be comparable to the ones in the focus groups. Residents and their next of kin will be recruited either dyadic (residents and their next of kin simultaneously) or monadic (residents or next of kin). In addition to this 'classic' qualitative data collection a pen-and paper survey containing the Impact of Event Scale-Revised will be conducted. The scale is a widely used tool to assess posttraumatic stress disorder. In contrast to usual procedures in standardized surveys, the data collection will be audio-recorded and field notes will be taken to gather additional qualitative data, including comments and field notes of the interviewees. We expect to gather in-depth understandings of local practice patterns of pandemic preparedness and undertaken NPIs in nursing homes and their effects on residents, their next of kin as well as on staff including responsibles and nurses in the context of the COVID-19 pandemic. Overall, the COV-19-DILEMMA study will provide evidence describing and explaining the effects of different NPI measures implemented in nursing homes on quality of life and other psychological and sociological measures of residents and their next of kin. The evidence will be informed by different data sources collected in an interdisciplinary way that can hardly be obtained by classical single methods approaches.",,2026,Institut für Biomedizinische Ethik und Medizingeschichte Universität Zürich,437384.89,Human Populations,Unspecified,Unspecified,Rural Population/Setting | Urban Population/Setting,Unspecified,Nurses and Nursing Staff | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Infection prevention and control | Secondary impacts of disease, response & control measures",IPC in health care settings | Indirect health impacts,2023 +P28972,196036,Host factors in severe COVID-19: learning from extreme cases,"The world is currently facing a pandemic due to a new Coronavirus (SARS-CoV-2) that emerged as cause of severe pneumonia in the city of Wuhan (China) in December 2019. Coronavirus 2019 disease (COVID-19) touched > 300'000 individuals and caused > 13'000 deaths worldwide as of March 21, 2020. While adverse COVID-19 outcome relies on age (e.g. >65 y. o.) and presence of comorbidities, severe forms of the disease are increasingly reported among young and previously healthy individuals. In the absence of specific antiviral drugs, the sudden influx of hundreds of patients requiring respiratory support represents a major threat to health care systems, forcing numerous countries to declare the state of emergency, with unprecedented measures to slow down the spread of the outbreak. In this application, we propose two strategies to identify patients at risk to develop severe COVID-19 at an early stage of infection.AIM 1. To identify host genetic variants associated with severe COVID-19We will perform whole genome sequencing (WGS) in ~100 patients* with an ""extreme"" presentation of COVID-19, defined by the need for mechanical ventilation in young patients with =1 comorbid condition (see details in M&M). Samples will be collected from an ongoing study in Lausanne (collection has already started and CRF is in place) and extended to additional hospitals/centres in Switzerland. Of note, DNA can be obtained from recovered patients after infection.Participants of the CoLaus study (middle-aged individuals from Lausanne) will be used as controls. SNP-array data is already available for this cohort and we also will perform whole-exome sequencing on 250 individuals. Moreover, individuals from the genome aggregation database (gnomAD) will be used as an additional control group with data from more than 125'000 individuals for exomes and 15'000 for genomes. This will allow for a 4-steps analysis strate-gy, including a genome-wide association study (GWAS) for common variants (SNPs), a GWAS for rare variants, a gene burden testing approach and a pathway burden testing approach.AIM 2. To identify early transcriptomic signatures associated with severe COVID-19We will perform whole blood RNA sequencing (RNAseq) in 50 patients with an ""extreme"" presentation of COVID-19, as defined above, and 50 patients hospitalized with a milder course of infection (no ICU). Sampling will be per-formed at hospital entry, at day 7-9 from symptoms onset and day 12-15 from symptoms onset (for patients with prolonged hospitalisation).Analysis will include the identification of sets of differentially expressed (DE) genes, gene set enrichment analysis (GSEA) to identify gene ontology terms and gene pathways showing significant up-regulation or down-regulation, digital cell quantification (DCQ) to identify differences in cell type abundance, and machine learning methods to iden-tify panel of genes whose abundance could be used to predict the disease outcome.Relevance. Given the increasing number of patients requiring respiratory support, it is urgent to identify high-risk individuals as soon as possible, as those may be benefit from prevention strategies (such as isolation, vaccination and prophylaxis). This is particularly relevant given the absence of knowledge on the level and duration of protective immunity after a first infection with SARS-CoV-2. This study will also provide new insights on the pathogenesis of COVID-19, including mechanisms leading to the excessive inflammatory responses in severe cases*Investigators are submitting another funding application (reallocation of another project interrupded due to the pandemic) to support logistics (study nurses etc). If accepted, may also contribute to increase the number of extreme cases up to 125-150.",,2023,Service des Maladies Infectieuses Département de Médecine Interne CHUV,307274.38,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P28982,220650,Monitoring Vaccination Discourse,"Background: Public communication is both a driver of vaccine acceptance as well as a driver of hesitancy and refusal. Therefore, it is highly relevant to understand how the media report on it, how the topic is debated in politics and in realms of public health organizations, and how people talk about vaccination in public. However, what exactly is the discourse about vaccines and vaccination in Switzerland? The project is focused on vaccine hesitancy in the German speaking part of Switzerland. Patterns of communication about vaccination have emerged over time and influence how vaccination are communicated during the COVID-19 pandemic, today, and in the future. The project identifies how this discourse shape topics, positions, knowledge on and attitude towards vaccination, including vaccine acceptance and levels of hesitancy. Objectives & Approach: The overarching objectives are to model, analyze, and simulate the vaccination discourse to develop and establish an application for monitoring public communication on vaccination in German-speaking Switzerland, and, moreover, to deliver first monitoring results about actual debates in the years 2024-2025.More specifically, we identify how discourses shape knowledge and communicative practices on vaccination. Positions in vaccination discourses have emerged over time and influence how vaccines and vaccination are communicated today. Therefore, we want to understand how linguistic practices produce verbalized public attitudes (e.g., frames) about vaccines and immunization in different domains and on different levels of social communication. In addition, the project also analyses the meta-discourse. Within this project, the term meta-discourse refers to the discourse on the vaccination discourse, e.g., problematisation, reinterpretation, and appropriation of specific terms, claims of absences and silencing, comments on the reporting or the communication. To achieve an understanding of how linguistic practices produce verbalized public attitudes, data from a longer period of time are needed: The pattern of what is written about vaccination in 2023 is largely influenced by what was written about vaccination a few years ago. In addition, long-term data are needed to develop and test the monitoring approach.The project's originality lies in the meta-discourse analysis, as well as in the development of a prototype for monitoring vaccination discourse in Switzerland. It will transform advanced basic and applied oriented research into transdisciplinary impact.This is implemented in two steps:1. The analysis of vaccination (meta-)discourse in the German-speaking part of Switzerland is necessary to determine the dynamics of the discourse and the characteristics of the topic in the various sub-discourses of media, politics, health organizations, and online forums. This analysis serves as a basis for simulating discursive structures and diachronic dynamics over time. 2. The prototype of a web browser application for vaccination discourse monitoring builds on these results by successively transforming them into a product. The development of the application will meet the requirements of a scientific tool that can be used by practitioners of public health organizations.Data: (i) Journalistic media (SMD) 2000-2024, (ii) German-speaking health online forums (ca. 20010-2024), (iii) parliamentary debates (parliamentary transcripts, Official Bulletin of the Swiss Parliament, 2000-2024), (iv) websites of public health organizations in Switzerland (200-2).Expected results and Impact:1. Basic and applied-oriented research: Corpus-centered discourse analysis with triangulated data and methods with an innovative approach to meta-discursive statements linguistic discourse analysis that allows the simulation of discourse networks arising out of realms of media, politics, public health, and lay communication. This enables to:2. Application-oriented research: Development of a prototype for monitoring vaccination discourse in Switzerland for simulating, i.e., a model-based procedure for determining preconditions for action in public discourse for pragmatic purposes. This leads to:3. Transdisciplinary outreach: Acquainting practitioners of the application to monitor, which can be used by public health organizations, NGOs, the Swiss national immunization program, and health care providers when designing communication aimed to improve addressing people (outreach).",,2027,ILC Institute of Language Competence Departement Angewandte Linguistik ZHAW,284413.87,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2024 +P28983,196328,Public COVID 19 pandemic discourses - a focus on vector populations (COVIDisc),"The containment of the COVID19 pandemic relies heavily on the communication between public health organizations, intermediaries, specific addressees and the general public. Therefore, mediatised public discourses and discursive practices of specific audiences play a crucial role in the policy implementation under the conditions of a ""besondere Lage"" (Swiss Epidemic Act of 2012, in force since 2016, EpG Art. 6). The study, through both the analysis of media and organizational discourses and qualitative interviews on discursive practices, focuses on the age group of 15-34 year-olds in German and Italian speaking Switzerland, who represent a critical vector population with respect to the corona pandemic inclusion of both Italian and German-speaking discourses can provide a deeper understanding of temporality and dynamics of the discourses and the impact of local and regional dynamics of the pandemic on the public discourses and discursive practices in other language regions of Switzerland.",,2021,ILC Institute of Language Competence Departement Angewandte Linguistik ZHAW,199125,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2020 +P28984,207625,Populism and Conspiracy in the COVID-19 Pandemic: Linking Discourses and Attitudes in Four European Countries,"In recent years, right-wing populist radical parties (PRRP) have enjoyed increasing success in European political systems, largely thanks to their calls for limiting immigration and fighting globalization. However, PRRPs have also adapted to a changing context by using new issues to strengthen their success and reformulate their agenda. In an era defined as 'post-truth', where personal beliefs and emotions are often more persuasive than objective facts, PRRPs could be expected to politicize crucial issues in today's democracies in their discourse by using conspiracy theories. The COVID-19 pandemic represents a relevant testing ground in this respect, and is expected to remain so in the future. Conspiracy theories can be defined as a proposed explanation for events that points to a small group of persons (the conspirators) acting in secret for their own benefit against the common good as the main causal factor (Keeley 1999). Conspiracy theories on health issues claiming that viruses are manufactured by governments or that vaccines are related to autism.The aim of this research project is to bridge populism and conspiracy theories to understand the politicisation of COVID-19. In order to pursue this goal, the project will link two separate but interrelated dimensions: a) the supplyside, i.e., analysis of populist radical-right discourse in the context of the coronavirus pandemic, to understand whether and to what extent conspiracy theories are present in their discourse and how the discursive claims are constructed; b) the demandside, i.e., analyzing the prevalence of conspiratorial beliefs and ideas among the public and their determinants, as well as the relationship between such conspiratorial ideas, on the one hand, and populist attitudes and support for populist parties, on the other hand. Empirically, we will focus a set of PRRPs in four countries - Switzerland, Austria, Italy and France - where such parties have been long established and particularly successful but differ in relevance in their respective political system (Mudde 2007; Bornschier 2010; Albertazzi & McDonnell 2015; Mazzoleni 2018; Bernhard & Kriesi 2019). To allow for a joint supplyside and a demandside analysis, this project will adopt a mixed-method approach (Seawright 2016; Tarrow 1995). First, we will compile an extensive collection of relevant speeches and texts on the topic by leaders and key representatives of the selected PRRPs. Then, we will analyse these documents both quantitatively and qualitatively to determine whether and to what extent conspiracy-related claims are present in PRRPs discourses and how they vary. Second, informed by the results of the analysis of populist actors' discourses, we will assess citizens' beliefs and attitudes related to COVID-related conspiracy theories. To this end, we plan to employ three types of survey experiments - a vignette experiment, a framing experiment, and a conjoint experiment. These are based on an original CAWI (Computer Assisted Web Interviewing) survey fielded in all four countries, designed to assess the effect and consequences of conspiracy theories and associated beliefs that would likely be masked in direct questioning (Hainmueller & Hopkins, 2015, Vivyan & Wagner, 2016).",,2026,Institut d'études politiques Faculté des SSP Université de Lausanne,516727.44,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2022 +P28988,210138,Promoting health-protective behaviors and well-being in pandemics: The role of social relationships,"Human behavior in general, and the adoption of preventive measures in a situation such as the Covid-19 pandemic, does not occur in a vacuum but is strongly influenced by social contexts, ranging from close social partners (family, friends) to social rules and policies. In light of the importance of social contexts for health-protective behaviors, the focus on the individual (e.g., personal attitudes, self-regulation) on the one hand or, on the other side of the extreme, on the role of the larger social context (e.g., lockdown, vaccination policies) in the research on Covid-19 has left an alarming gap in our knowledge about the impact of social partners and the more immediate social group in supporting or hindering behaviors that can prevent the spread of infections. Similarly, the emergence and effects of social conflicts caused by Covid-19 containment measures have not yet been sufficiently addressed. This is the aim of the proposed project. In particular, we propose to use a multi-methods approach comprising correlational, intervention, and experimental designs to test the impact of social processes in adult family and friendship dyads, social groups, and policy measures on health-protective behaviors, and on social and individual well-being in the current pandemic and future crises. All proposed studies will use a citizen science approach to ensure high acceptance and dissemination in the general public. Overall, the proposed project will contribute to a better understanding of which social factors foster (or hinder) preventive behaviors and social as well as individual well-being in pandemic and comparable crises. The project will thus provide intervention and experimental evidence on how the beneficial effects of social relationships on these key outcomes can be applied to the general population.",,2026,Angewande Sozial- und Gesundheitspsychologie Psychologisches Institut Universität Zürich,545444.35,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P28989,196405,Predicting the endorsement of preventive behaviors in the context of the Corona virus pandemic: Examining temporal dynamics and the role of risk communication,"The current situation of the ongoing new Corona virus pandemic offers a rare chance to investigate the dynamics of the relation between perceived risks for oneself and one's social environment, known health-behavior related factors (i.e., self-efficacy, perceived efficacy of different preventive behaviors, perceived social norms), and the self-reported intention and adoption of protective behaviors over time. We propose two studies to investigate the changes in risk perception, health-behavior related factors, and self-reported preventive behaviors over time in a representative sample of the Swiss population (Study 1) and the role of risk communication for the endorsement of preventive measures (Study 2).As the prevention of a further spreading of the virus crucially depends on measures of ""social distancing,"" we maintain that it is essential to investigate the role of the perceived risk to oneself and others as one of the key predictors of the intention to adopt social distancing behaviors. We hypothesize that younger adults are less likely than older adults to perceive the risk they pose to transmitting the new Corona virus and the resulting potential harm to others. The lower perceived other-related risk, in turn, is hypothesized to lower the likelihood of adopting social distancing behaviors. Based on research demonstrating the effect of risk communication on prosocial behavior (Slovic, 2007), we propose an experiment that compares if different ways to communicate the risk of contracting the Covid-19 virus either to an individual or to a group of people (Study 2) affect particularly younger adults' endorsement of preventive behaviors in general and social distancing in particular, as well as pandemic-related prosocial behavior. Given that the level and importance of determinants are bound to change across the development of the pandemic, we propose Study 1 as an 8 months longitudinal study with a sample representative of the general adult population of Switzerland. Given the urgency to start data collection, the University of Zurich has agreed to fund a first measurement point taking place during the last week of March 2020. As time is key not only for handling the breakout, but also for assessing the changes in determinants of the preventive behaviors, a second measurement point is planned for the first week of May 2020, pending the funding of this second assessment through a grant proposal submitted to the <>. With this proposal, we hope to be able to turn Study 1 into a longitudinal study covering in total a period of 8 months with monthly assessments. Such a longitudinal, multi-measurement, representative study on the dynamic interplay of risk perception, and other evidence-based factors contributing to health behavior, and the currently only available measures to curb the further spread of the pandemic, namely the adoption of preventive behaviors by individuals, has never been conducted before. A unique and novel study like this in combination with experimental data on prosocial behavior during pandemics are of key importance for informing future theory- and evidence-based effective interventions in the case of epidemics or pandemics.",,2022,Sozialpsychologie Psychologisches Institut Universität Zürich,379111.77,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Approaches to public health interventions,2020 +P28990,196910,Swiss SOLIDARITY: An international public health emergency SOLIDARITY trial of treatments for COVID-19 infection in hospitalized patients,"WHO SOLIDARITY trialThere are currently no available vaccines or treatments for COVID-19. Although there have been some suggestions for untested treatments that could be added to the usual care in hospitals, none is known to help. The World Health Organization (WHO) is, therefore, organizing a study in many countries in which some of these untested treatments are compared with each other, to discover whether any do help. The study treatments are remdesivir, chloroquine or hydroxychloroquine, lopinavir plus ritonavir, and interferon-beta. Some are given as daily pills, and some as daily injections.Patients invited to join the study will be those who are admitted to a collaborating hospital. Patients diagnosed with COVID-19 and who have consented to be part of the study will be randomly allocated to receive either local standard care alone or local standard care and one of a list of study drugs. During the study, some treatments may get removed from this list, and others may be added to it. Each patient will only receive one of the treatments. The patients will be followed up for the entire length of their hospital stay. Death from any cause will be recorded and this will be the main result used to determine whether a drug is effective. Length of hospital stay and time to first receiving ventilation (or intensive care) will also be recorded and used to determine the drug's effectiveness.The study is conducted between March 2020 and March 2021.",,2023,Service des Maladies Infectieuses Département de Médecine Interne CHUV,1659880.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Therapeutics research, development and implementation",Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +P29013,220582,Safe Glow: Illuminating the Future of Sterilization with Human-Safe Light Emitting Diodes Technology,"In response to the urgent need for effective, sustainable, and safe sterilization methods, exacerbated by the COVID-19 pandemic and the global energy crisis, our project aims to revolutionize current technology through the development of a novel ultraviolet (UV) light solution. Traditional UV light sources, though effective in killing microorganisms, often emit harmful wavelengths, posing risks to human health. To address this, our project proposes a groundbreaking approach: a new generation of UV light-emitting diodes (UV-LEDs) utilizing advanced two-dimensional (2D) materials.Focusing on the unique properties of high-quality intrinsic hexagonal boron nitride (h-BN) and doped h-BN, our project aims to create UV-LEDs emitting safe UV light. Diverging from conventional methods, our approach employs 2D materials h-BN layers, emphasizing an efficient active boron nitride layers with careful engineering.Through meticulous integration of surface science and 2D materials fabrication, we plan to develop a prototype UV-LEDs device with heightened efficiency and an extended lifespan. By bridging the gap between fundamental research in 2D thin film fabrication and real-world applications, the project addresses a field of high relevance.Aligned with the European Commission's sustainability and energy efficiency measures, our research contributes to phasing out inefficient lighting technologies. The anticipated impact extends to healthcare, public safety, air and water purification, agriculture, medical equipment, and environmental monitoring. This project represents a significant stride toward a brighter future, with the potential to enhance the quality of life globally.",,2025,Physik-Institut Universität Zürich,113778.62,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2024 +P29026,198258,Development of a real-time biosensing system of SARS-CoV-2 to improve healthcare workers safety during COVID 19 pandemics,"Recent results demonstrated an increased risk of COVID-19 infection among healthcare workers (HCW), particularly when access to personal protective equipment (PPE) was inadequate. During the COVID-19 pandemic, access to PPE has become complicated by a surge in worldwide demand combined with production limitations and logistical barriers. Since their introduction in hospitals in the 1990s, filtering facepiece (FFP) masks, mostly of the FFP2 type, are used by HCWs to protect themselves against bioaerosols due to tuberculosis, measles and selected respiratory viruses. The COVID-19 pandemic due to the novel SARS-CoV-2 has sparked debate around judicious and safe use of face masks for the protection of HCWs who provide direct care for COVID-19 patients. At the heart of the discussion is the question whether SARS-CoV-2 is transmitted by droplets or aerosols, or by both. While the former are large (>5µm) and fall rapidly to the ground, the latter are small (<5µm) and can stay in the air and travel much farther than the 1-2 metres normally considered a safe distance to infected patients. Today, we have little information on physical spread and infectious dose of SARS-CoV-2, and the discussion about the choice of face masks is based on indirect data. The starting hypothesis of this project is that decision-making regarding mask-wearing for HCW in the current situation of inadequate mask supply, coupled with uncertainty regarding airborne COVID-19 transmission, can be improved if direct detection of SARS-CoV-2 in aerosols can be implemented in clinical situations where aerosolisation is expected. This would be achieved by installing biosensors. Currently, the reverse transcription polymerase chain reaction (RT-PCR) technology is the most sensitive method for SARS-CoV-2 detection in respiratory secretions and it is routinely used to diagnose COVID-19. A reliable biosensing system that can detect SARS-CoV-2 rapidly, quantitatively and in real-time, supplementing RT-PCR technology would significantly help to understand SARS-CoV-2 transmission and inform recommendations for safe and practical use of PPE, and particularly face masks. In this project, we will validate a novel dual-functional, localized surface plasmon resonance (LSPR) biosensor to improve detection and on-line monitoring of SARS-CoV-2 in clinical settings. The two-dimensional gold nano-islands (AuNIs), functionalized with complementary DNA, can perform sensitive detection of selected sequences from SARS-CoV-2 through nucleic acid hybridization. For better sensing performance, the plasmonic photothermal effect, generated by the same AuNIs chip, and an additional laser irradiance can elevate the local temperature and facilitate the specific discrimination of two similar gene sequences. We aim to integrate a bioaerosol sampling system with a specific biosensor, to allow continuous real-time monitoring the shedding of SARS-CoV-2 virus in droplets or aerosols, aiming to rapidly and continuously collect airborne virus with a high collection efficiency and stable microbial recovery. The collected virus can be efficiently enriched in the sampling liquid and subsequently introduced into the integrated micro-system for virus lysis and nucleic acid extraction. This system is to be tested in clinical situations and with real COVID-19 patients with the aim to understand transmission of SARS-CoV-2 in patient surroundings. In parallel, a cluster-randomised, controlled, cross-over study will evaluate the benefits of wearing surgical masks vs. FFP2 masks during COVID-19 patient care (outside aerosol-generating procedures). To date, no study has combined virus detection technology with a cluster-randomised trial to address the question of appropriate face mask usage in COVID-19 care.",,2023,Klinik für Infektionskrankheiten und Spitalhygiene Universitätsspital Zürich,867858.51,Human Populations | Environment | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical | Non-Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Barriers, PPE, environmental, animal and vector control measures",2020 +P29029,198464,"Daily life experiences of Covid-19: an ethnographic exploration of viral exposure, protective practices and the making of vulnerabilities through the lens of living conditions in Canton de Vaud","What makes people vulnerable in pandemic times, the virus and/or other socioeconomic and environmental factors? As Switzerland, progressively releases Covid-19 confinement, some groups of the population emerge as more affected than others by viral exposure and protection measures. As recalled by the National COVID-19 Science Task Force (NCS-TF), ""the effects of the pandemic and of pandemic response are likely to play out in an unequal manner not only along gender lines, but also in an intersectional manner along other categories such as social class, sexuality, ethnicity, migration, etc."". In the context of the Covid-19 pandemic, social relations and the living environment have emerged as playing a crucial role in risk of exposure, viral transmission, and protection, as well as possible inequalities resulting from them. (Semi)confinement, so-called ""social distancing"", and masks wearing, aim to create physical barriers to contain viral propagation, but target also how people relate to each other. The jointure of biological and social levels raise questions about the impact of professional activities and family/social relations in spreading the virus (Bayer and Kuhn 2020) as well as about the unintended effects of protective practices on individuals, such as social isolation, loneliness (Miller et al. 2020) or domestic violence(developing et al. 2020; Lima et al. 2020), and on their rights (Rio and Malani 2020). Due to the novelty of Covid-19 disease, there is an urgent need for data qualitative about the social and environmental factors which modulate the transmission of the disease, the adoption of protection measures, and may increase health differentials.In order to fil this knowledge gap, this medical anthropology project explores the configurations of living conditions - the ""everyday environment of people, where they live, play and work, which are the product of social and economic circumstances and the physical environment - all of which can impact upon health - and are largely outside of the immediate control of the individual"" (WHO 1998) in three different populations of the Canton de Vaud a) index cases; b) ""essential services"" professionals; c) asylum seekers,. This particularly densely populated Canton, bordering France, was one of the most affected by Covid-19 pandemic, challenging political and health authorities in regard to preparedness, management and prevention strategies. This medical anthropological study is developed as an integral part of an epidemiological project - SérocoViD - part of the Swiss School of Public Health program - Corona Immunitas - for determining Covid-19 immunity at cantonal and national levels. It aims to complement the epidemiological quantitative methods used in SérocoViD, by shedding light on how living conditions impact viral exposure, the adoption of protective practices and the emergence of additional vulnerabilities which might increase health inequities related to gender, ethnicity, and socioeconomic status. It will undertake an ethnographic exploration of living conditions in these three populations differentially exposed to Covid-19 pandemic times with a focus on reconfigurations of professional activities, couple/family/social relations, and housing, during the pandemic. Building on solid interdisciplinary collaboration, this project will contribute to the development of public health strategies empirically grounded in people's living conditions and integrating the interplay of environmental, social, and biological in the production of health differentials.",,2022,Policlinique Médicale Universitaire PMU,272508.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29031,210257,10th International Symposium on Isotopomers (ISI) and 12th Isotopes Conference,"Stable isotopes provide a robust, yet under-utilized tool to trace source, loss and conversion processes. Applications cover diverse research areas, e.g. ecology, geology, food / medical sciences, which are at the core of many global, societal challenges, from climate change to biodiversity loss to food and nutrition security. For a successful project in stable isotope research, expertise in several cross-cutting subjects, analytics (mass spectrometry vs. laser spectroscopy), reaction mechanisms and experimental design / modelling approaches is required.We will organize the first joint 10th International Symposium of Isotopomers (ISI) and 12th Isotopes Conference (ISI+Isotopes 2022) at Empa Dübendorf, Switzerland to bring together novice users and experts and discuss current concepts and future perspectives of stable isotope research. The conference will be realized in a hybrid format to both foster face-to-face discussions / networking and facilitate participation of scientist from distant locations or areas with current (COVID-related) travelling restrictions. Scientific sessions will centre on key topics in stable isotope sciences, chaired by international experts and introduced by attractive keynote and invited presentations. In addition, contributed talks and poster sessions will be scheduled to provide students / postdocs the opportunity to present and discuss their results, a chance, which has been rare since the start of the pandemic.The conference will take place at the Empa Academy in Dübendorf, which provides meeting rooms with up-to-date conference technology for hybrid events. The Academy team, led by Claudia Gonzalez, will support the local organizers with the organization, homepage, flyer design etc. Within this SNSF scientific exchange grant, we would like to apply for support with respect to travel / accommodation costs for invited participants and fees for student helpers providing assistance with the online realization.",,2022,"Luftfremdstoffe / Umwelttechnik 500 - Mobility, Energy and Environment EMPA",17426.71,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Switzerland,,"Secondary impacts of disease, response & control measures",,2022 +P29057,200180,"Prevention, Planning, and Policy: A COVID-19 Vaccine and Beyond","Background and rationale: With the coronavirus crisis disrupting people's daily lives across the globe, governments and health systems are struggling to address the economic and health consequences of this international public health emergency. Vaccination is one of the available measures in the public health toolkit to mitigate the spread of infectious disease. With more than 165 COVID-19 vaccines currently in development throughout the world and estimates for availability in early 2021, the COVID-19 vaccine is scheduled to be the vaccine with the fastest trajectory from laboratory to market in history. Taken as a social object around which there are myriad social and political negotiations, vaccination has been framed in public discourse and scientific narratives as a champion of health for all citizens. As a technoscientific solution, vaccination is placed at the fore of such narratives wherein scientists, biomedicine, and healthcare professionals (HCPs) are portrayed as heroes in humans' collective battle against tiny microbes. That said, such visions do not sufficiently encompass how vaccination as a social practice involves a multitude of social interactions, including health policy and political decision-making, patient-provider interactions, public health messaging, and public debates in various media channels. Overall objectives: The proposed research builds upon an ongoing project (July 2020-December 2021) entitled Coronavax: Preparing Community and Government which investigates preparedness for the rollout of the anticipated COVID-19 vaccine in Western Australia (WA). This postdoctoral research extends the scope of the Coronavax project by allowing me to independently lead research into COVID-19 vaccine rollout in real time (September 1, 2021-February 28, 2023). I will study the effects of the COVID-19 crisis on main determinants of vaccine hesitancy (VH) and vaccine uptake in Australia. Specific aims: My focus will be on COVID-19 vaccine rollout in real-time in Australia. To account for the broader context of vaccine attitudes in a pandemic scenario, I will assess childhood vaccination/influenza vaccine sentiment and uptake since the beginning of COVID-19. Specifically, I will analyze how people's vaccination (COVID-19, childhood, and influenza) attitudes and uptake are linked to sentiment about officials' handling of the COVID-19 crisis, VH in relation to each vaccine, and levels of (dis)trust in science, healthworkers, government, and pharmaceutical companies. I will also examine COVID-19 vaccination rollout from the perspectives of public health and governmental officials, with a content focus on the role of the State in creating and implementing vaccination policy. Methods to be used: This study benefits from a convergent mixed-methods study design, meaning that both qualitative and quantitative methods will be employed simultaneously on the same topic. There are 3 study components, 2 qualitative and 1 quantitative: (1) semi-structured interviews (N=35-40) with various sub-sections of WA populations, such as people =65 years of age, parents and caregivers of children 0-10 years, culturally/linguistically diverse communities, urban indigenous Australians, pregnant women, and vaccine hesitant individuals; (2) semi-structured interviews and/or focus group discussions (N=10-15) with public health authorities, governmental officials, and HCPs; and (3) a brief internet-based national survey of a national sample of individuals living in Australia. Expected results and impact: This research provides local insights in Australia into social phenomena surrounding COVID-19 public health governance and vaccination implementation. The empirical analysis provides opportunities to establish a multicomponent framework for future infectious disease prevention planning and comparative health social science research on a larger scale. The results of this research are of immediate import as they document and analyze the implementation of current public health efforts aimed at curbing the consequences of the coronavirus epidemic.",,2023,"School of design Faculty of Arts, Business, Law and Educatio University of Western Australia",125061.39,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Swiss National Science Foundation (SNSF),Switzerland,Europe,Europe,Unspecified,,,,Australia,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +P29082,CSA2020E-3134,Masters' Programme in Epidemiology and Biostatistics with Specialization in Disease Outbreak and Epidemic Response in sub-Saharan Africa,"Epidemic-prone diseases are a global public threat particularly in sub-Saharan Africa where there is a scarcity of skilled public health workforce. The COVID-19 pandemic in Africa has informed the urgent need for a critical mass of well-trained epidemiologists and biostatisticians to respond to disease outbreaks and epidemics. The objective of the capacity building programme is to train a cohort of epidemiologists and biostatisticians across sub-Saharan Africa, who can collectively conduct routine surveillance, public health research and respond timeously to disease outbreaks. These EPI Fellows (early to mid-career researchers) will enhance the public health workforce capacity in NPHISs and National Ministries of Health to enable them to respond to outbreaks promptly. The Department of Epidemiology and Medical Statistics (EMS) at the University of Ibadan is well-positioned to provide competence-based training for Africans based on its 20-year track record of postgraduate training. The MPH Epidemiology and Biostatistics programme is supported by a consortium of academic and public health institutions in order to facilitate knowledge and competency-based training through a blended approach involving virtual and in-person modalities. This home-grown training will result in lower cost, better retention of graduates in the sub-Saharan Africa region, and an instructional focus and context that is relevant to each country. The 15 candidates (EPI Fellows) are public health practitioners working at National Public Health Institutes and National Ministries of Health as well as State Ministries of Health (SMoH). Medical doctors, veterinarians and graduates in the health sciences (pharmacists, laboratorians and biostatisticians) were admitted into the programme and they are currently on field attachment.  The EPI Fellows attended didactic lectures at the University of Ibadan (UI). A hybrid approach was used for the delivery of the lectures. This approach was adopted to allow the international partners (Institute of Cancer Research, UK, and University of Warwick, UK) to deliver the lectures and exercises.  The lectures were divided into two semesters (11 courses), each semester was also divided into two clusters (6 and 5 courses respectively). The fellows also participated in several online courses and presented at two national conferences. A proposal writing workshop was organised after the second semester examinations. Two workshops were organised for the Fellows: (1) How to make a power point presentation, and (2) Proposal writing. After these workshops, the Fellows made their pre-field seminar (research proposal) presentation, where each Fellow presented their proposed research. Following this, ethical approval was obtained. Currently, the Fellows are on a 6-month internship at various field sites.     On completion of the programme, the EPI Fellows will be skilled in infectious disease epidemiology concepts, have good research capacity in epidemiology and biostatistics, be prepared to analyse data and manage epidemic disease outbreaks, and produce forecasts and analytics to support public health decision making. They will also have enhanced research capacity in poverty-related diseases and in clinical trials across Africa. The EPI Fellows will remain in Africa for a minimum of two years after completing their studies to empower their countries.  The EPI Fellows will demonstrate good knowledge and application of statistical methods in epidemiological research and disease outbreaks; will have acquired skills in scientific reporting and practical experience to provide analytic and consultative services in epidemiology and public health research; acquired skills and practical experience to investigate epidemics and manage disease surveillance systems; developed skills in the design, organisation and management of epidemiological units as leadership and management skills; developed new methodologies and approaches for outbreak investigations and published in reputable peer reviewed journals to add to the body of literature on outbreak response in Africa. https://www.com.ui.edu.ng/index.php/prof-olufunmilayo-i-fawole/2-sample-data/712-masters-training-in-epidemiology-and-biostatistics-2021-2022-academic-year  ",,2023,College of Medicine - University of Ibadan,893096.66,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Netherlands,Europe,Africa,Europe,,,,Nigeria,United Kingdom | United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P29083,CSA2020E-3126,Consortium for Development of Sustainable Research Based Fellowship Training on Infectious Disease Epidemiology and Biostatistics in Africa,"The IDEA Fellowship programme is consortium driven. There are eight consortia institutions including seven in Africa and one in the UK. The main purpose of this project is to build capacity in Africa to respond to infectious disease outbreaks through training of field epidemiologists and biostatisticians. Disease outbreaks that are affecting most of sub-Saharan Africa (SSA) include those that are newly emerging, like COVID 19. Multi-drug resistant bacteria or viruses have also newly emerged. Some of these include multi-drug resistant tuberculosis, malaria, HIV, multi-drug resistant bacteria and fungi. Others are infectious diseases that were previously there, disappeared and are re-emerging, such as Ebola virus, Marburg virus, Congo Crimean Haemorrhagic fever, Aflatoxin, Bubonic pneumonia, and polio among others. There are also infectious diseases that have been on the sub-continent for a long time, but have recently increased in both frequency and impact on health services, such as malaria, pneumonia, cholera, measles, and mumps. These diseases have been known to cause epidemics in some settings. The WHO Joint External Evaluation (JEE), conducted in June 2017, to assess Uganda's level of compliance with the set standards, noted that some progress had been done; however, the areas that were lagging behind include appropriately trained infectious diseases field epidemiologists. The IDEA Fellowship Programme was designed in response to this gap in capacity building. The vision of the IDEA Fellowship Programme is to build capacity through training of scientists on infectious disease epidemiology, capable of conducting disease surveillance, outbreak investigations and timely response, and translating data into evidence-based practice in Uganda. This is the first-degree awarding programme for Infectious Disease Field Epidemiology and paves the way for a career path for the Fellows. The programme includes 24 months hands-on-training in field epidemiology and biostatistics at Busitema University. The initial intake of 15 Fellows were admitted into the programme taking into account gender and merit. The implementing organisations include seven complementary and synergistic partners: Busitema University; Uganda National Public Health Institute; Ministry of Science, Technology and Innovation; Uganda National Health Laboratory and Diagnostic Services; Uganda Virus Research Institute; Mbale Clinical Research Institute and The Open University. The IDEA Fellowship will strengthen the Uganda Ministry of Health's capacity for infectious disease surveillance and outbreak response, contribute to the development of a critical mass of scientists, establish a career track in field epidemiology, and boost the participating institution's research capacity and synergies in terms of South-South and South-North collaborations.  ",,2024,Busitema University,882063.24,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Bunyaviridae | Coronavirus | Filoviridae | Yersiniaceae | Novel Pathogen,,,,,,,,,Crimean-Congo haemorrhagic fever | COVID-19 | Ebola virus disease | Marburg virus disease | Plague | Disease X,European & Developing Countries Clinical Trials Partnership (EDCTP),Netherlands,Europe,Africa,Africa | Europe,,,,Uganda,United Kingdom | Uganda | Uganda | Uganda | Uganda | Uganda | Uganda,Epidemiological studies,,2021 +P29087,CSA2020NoE-3100,Central Africa Regional Network on Clinical Research (CANTAM): Strengthening Clinical Infectious Diseases Research in Central Africa,"The clinical research network of excellence for Central Africa (CANTAM) was established in 2008 with the aim of strengthening the individual, institutional and infrastructural capacities in three Central African countries (Cameroon, Gabon and Republic of Congo) along with Germany to conduct clinical trials on tuberculosis (TB), HIV/AIDS and malaria. The basis was to conduct epidemiological studies, and train staff in good clinical and laboratory practices, whilst strengthening the clinical trials infrastructure. Over the years, it appeared necessary to increase partners as specific skills were lacking. With the addition of the Democratic Republic of Congo, Zambia, United Kingdom and the Netherlands, the CANTAM2 network was formed in 2016. In CANTAM2, clinical research capacities on TB were strengthened, and the first multicenter clinical trial on malaria was successfully conducted (ClinicalTrials.gov ID: NCT03201770). Notwithstanding these successes, clinical research in Central Africa is still facing significant gaps, exemplified by the limited number of clinical trials conducted to date. It is for this reason that for the years 2021-2023, the objectives of the CANTAM are to: 1) Set-up and conduct epidemiological studies on HIV/AIDS, tuberculosis (TB), malaria, neglegted tropical diseases (NTDs) and COVID-19 to collate baseline data for future clinical trials; 2) Design and implement training activities necessary to conduct clinical studies on traditional medicines for parasite and viral infections; 3) Prepare the sites for future Phase I to IV clinical studies, by specifically strengthening pharmacovigilance including regulatory authorities and national or institutional ethics committees; 4) Developing adapted training platform and mentorship programmes. Five indicators of success have been identified for CANTAM3: 8 new female scientists established, accreditation of new laboratories, increase in the number of clinical trials, mapping of disease incidences in all CANTAM countries and established pharmacovigilance activities in the region. Given the fragile health systems in Central Africa, new and re-emerging infectious disease outbreaks, such as the COVID-19 pandemic can paralyse health systems and existing structures. CANTAM3 envisage to synergize our existing efforts at local and regional level, while considering our strengths and weaknesses of the network identified by our own evaluation. In CANTAM3 we propose an innovative governance structure that will leverage added responsibilities and ownership to each partner country within the CANTAM network, implementing internal incentives for the best contributors. As a result, CANTAM3 will be able to make a significant contribution in the field of malaria, HIV/AIDS, TB, NTDs as well as other viral diseases, such as COVID-19.",,2024,Fondation Congolaise pour la Recherche Médicale,5359377.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,European & Developing Countries Clinical Trials Partnership (EDCTP),Netherlands,Europe,Africa,Africa | Europe,,,,Congo,Cameroon | Cameroon | Cameroon | Gabon | Gabon | Gabon | Zambia | Netherlands | United Kingdom | Germany,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2021 +P29090,CSA2020E-3131,Training Epidemiologists and Biostatisticians for enhanced response to disease outbreak and epidemic in West-Africa,"Sub-saharan Africa is suffering from unavailability or severely limited reliable epidemiological data and settings for public health. This is further aggravated by a shortage of skilled personnel in epidemiology and biostatistics to efficiently monitor, analyse and interpret data to inform policy and decision making. By 2063, the first aspiration of the Africa Union is to build a prosperous Africa based on inclusive and sustainable development (African Union Commission, 2015). Two of the expected outcomes for this aspiration are: (i) African people have high level and quality of life, a good health and well-being and (ii) citizens are well trained and sufficiently qualified having as support the science, technology, and innovation. The centrality of good health to well-being is expressed in the global recognition of health as a basic human right and in the Sustainable Development Goal (SDG) 3, which is to ""ensure healthy lives and promote well-being for all at all ages"". Epidemiology and biostatistics stand at the core of this great goal. From 2014 to 2019, sub-Saharan Africa has faced various epidemics of which the Ebola epidemic caused important human loss in Sierra Leone, Liberia and the Democratic Republic of Congo. From 2019, the COVID-19 outbreak caused dramatic loss of lives, social and economic damages in the world, and controlling its spread and impacts has been the main worldwide challenge. The need to fill the shortage of skilled personnel in epidemiology and biostatistics has lead to the project ""Training Epidemiologists and Biostatisticians for enhanced response to disease outbreak and epidemic in West- Africa"". The overall aim is to enhance West-Africa's research capacity in epidemiology and biostatistics to efficiently respond to disease outbreaks and emerging (and re-emerging) infectious diseases. Specifically, the project aims to (i) train fifteen skilled postgraduate biostatisticians and infectious disease epidemiologists in West Africa; (ii) strengthen the ability of young scientists from West African countries to manage epidemic disease outbreaks and (iii) strengthen regional and international cooperation in biostatistics and epidemiological research. The project offers two regional qualified two-year Master of Science programmes in epidemiology and biostatistics, respectively with opportunity for credit seeking through the distance learning platform of the London School of Hygiene and Tropical Medicine (LSHTM). The project's consortium includes one sub-Saharan country (Benin) and one participating state (United Kingdom). The programmes aim to teach up to date knowledge about determinants of health, responses to diseases, mitigation of environmental problems and successful policies. In addition, the priority will be to make sure that knowledge is valued as a global public good and disseminated quickly, effectively, widely, and is freely accessible. The curricula includes a six-month research component. In year one, curricula of the two Master's programmes was improved. Fifteen students from eight countries (Benin, Togo, Côte d'Ivoire, Ghana, Mali, Niger, Guinea, and Liberia) were selected and registered in the Master's programmes, among which there are seven women and eight men. They have all successfully completed the first year of the programme and been admitted to the second year. They have also been paired with experienced mentors for the project duration. By the end of the first year, research projects were discussed with the Fellows and their home institutions to ensure that topics are relevant for their home country, but also the West-Africa region. In year two, the Fellows took lectures in their respective programmes and one additional class with LSHTM in the frame of a distance learning programme. They had relaxation time with the project coordination team where they (i) shared their thoughts about the project and its implementation, and (ii) learned success stories from the project team members who are renowned scientists in the field of biostatistics, epidemiology, and public health. A workshop on mentoring was held for the Fellows and their mentors. The TEBWA fellows were also trained in writing a research proposal, drafting a scientific article, and making impactful communication during a conference. They have also been trained on how to successfully conduct a systematic review. The TEBWA fellows also presented their research proposals and received comments and advice from the project team members. They are currently implementing their projects, the outputs of which are relevant for regional and global public health. The TEBWA fellows have also joined at least two relevant scholar societies for at least three years. Each TEBWA fellow was also supported to take additional online courses (MOOC). All TEBWA fellows will attend the Eleventh EDCTP Forum (November, 2023). More details on the project can be found here: http://tebwa.labef-uac.org/.",,2024,Université d'Abomey-Calavi,892843.57,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Netherlands,Europe,Africa,Africa | Europe,,,,Benin,Benin | United Kingdom,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P29092,CSA2020E-3123,MSc EpiBiostat,"The recent COVID-19 pandemic highlighted the need for effective capacity to detect and respond to public health emergencies at different levels, namely global, regional, and country level. The Democratic Republic of Congo, the second largest African country with a population of up to a hundred million people, has been facing disease outbreaks with impacts on health, economy and the well being of communities. Most of these outbreaks start in rural areas with delay on detection where surveillance capacity is weak. Surveillance, preparedness, and response to these emergencies requires the country to have a skilled and well-trained workforce. However, the country still experiences a huge gap in terms of trained epidemiologists. The University of Kinshasa School of Public Health is contributing to closing these gaps. Ten years ago, with support from US CDC and AFENET, it established a field epidemiology and laboratory training programme - the first of its kind in the country. This programme has trained most epidemiologists working at different levels of the health system in the country. However, the need is still very high compared to the population size to be covered. In 2021, the School received a grant from EDCTP to support the government by providing training to a cohort of 15 epidemiologists. Launched the same year, out of more than 100 applications, 15 Fellows were selected for a fully funded Master of Epidemiology and Biostatistics. This three-year project will provide not only training and capacity building, but also networking and mentorship support from experienced epidemiologists. One year later, the Fellows have completed their first semester as well as an internship period of six months. Regarding first semester courses, Fellows were exposed to key modules such as an Introduction to epidemiology, Biostatistics, Disease surveillance, Research methods (including quantitative and qualitative methods), Introduction to One Health, Introduction to public health, and Informatics (data analysis tools). All the Fellows passed their semester examinations and completed the requirements for their first semester before the internship. Regarding the internship, Fellows worked with their mentors who are FELTP alumni to support disease surveillance activities, conduct data analysis and outbreak investigation, which contributed to the health system of the communities covered by their activities. During their internship period, Fellows benefited from the experience of the mentors. Regular meetings with mentors helped Fellows to acquire more from their experiences. For networking activities, Fellows are now part of the EDCTP Alumni Network where they interact with other Fellows across the continent. They also prepared and submitted abstracts to the upcoming Africa Field Epidemiology Conference where they will network with other Fellows trained across the continent.   Fellows have commenced their second year with one semester of classes and one semester of internship. They are expected to complete their studies in 2023 and will be supported by the project for their placement with mentorship and networking activities. They are part of 150 Epi Fellows funded by a partnership between EDCTP and Africa CDC for a €7.5 million initiative to support institutions in Africa and Europe to train a cadre of public health workforce that will boost epidemiological and biostatistical capacity on the African continent through Master's degree programmes in epidemiology and biostatistics. After their training, the Fellows are expected to increase the capacity to respond to public health challenges at the subnational, national, and regional level.",,2024,Kinshasa School of Public Health,876675.75,Human Populations,Unspecified,Unspecified,Rural Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,European & Developing Countries Clinical Trials Partnership (EDCTP),Netherlands,Europe,Africa,Unspecified,,,,Congo (DRC),,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P29097,346796,Advancing Enzymes for Precision Therapeutics,"The AdEPT project addresses the global need for safer, more sustainable and cost-effective production of RNA therapeutics, recently highlighted by the COVID-19 pandemic's need for rapid vaccine production. By combining the expertise and resources of ArcticZymes Technologies ASA, UiT - The Arctic University of Norway and SINTEF, AdEPT aims to strengthen ArcticZymes' innovation capacity and develop improved enzyme solutions for efficient production of RNA-based vaccines and therapeutics. Key R&D challenges include the design and new essential enzymes in the mRNA production process using techniques such as molecular modeling and AI- and structure-guided modifications. Improvements to methodology in protein expression and purification are also needed to ensure that the functionality and quality of enzymes meet industry standards. A successful collaborative project will improve the production and analysis of RNA therapeutics for future better health.",,2027,ARCTICZYMES AS,1162093.36,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Pre-clinical studies,2024 +P29098,343168,Impaired microcirculation and tissue hypoxia as a possible mechanism in ME/CFS,"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease that usually occurs after an infection, in some cases also in patients with late effects after COVID-19 (Long-COVID). The disease mechanism is still unknown, and we lack biomarkers and effective treatments. However, there is an increasing number of research reports documenting biological changes in ME/CFS patients, and recent findings suggest that limitations in the blood supply may be an important factor. Based on these findings, we have a hypothesis that tissue hypoxia due to reduced blood circulation in small blood vessels disrupts the cells' energy metabolism in the patients. To test this hypothesis, we will analyze biochemical signatures of hypoxia in blood samples from ME/CFS and Long-COVID patients, taken at rest or during physical testing. We will also look at changes in blood and blood vessel cells and small particles that they can release, which may reveal new details about the disease mechanism. Our project aims to pursue the mechanisms behind ME/CFS through hypothesis-driven investigations in patient samples and laboratory studies, using new approaches. We will search for indications of impaired microcirculation and tissue hypoxia that can be triggered in an effort-dependent manner. We will address research questions related to mechanisms in blood and blood vessels that may be responsible for reduced tissue perfusion. This will also include mechanisms that can link reduced microcirculation to specific changes in the immune system. The findings will be able to provide new insight into the mechanisms behind ME/CFS and Long-COVID, reveal new directions for future research, and provide new opportunities for the development of biomarkers and treatment. The project will involve collaboration with leading researchers with complementary expertise and resources in the area.",,2027,UNIVERSITETET I BERGEN,1083307.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2024 +P29101,341642,"UltraZyme - Enzymatic tools for ultrafast, sensitive and specific detection of viral infectious diseases at Point-Of-Care","Viral pandemics such as COVID-19 represent a global health threat, and as we have all experienced, we need effective surveillance strategies to combat such large disease outbreaks. Identification of people carrying the virus is critical, and early detection is our best chance of preventing these outbreaks. Simple, super-fast and accurate tests that can be used at home or close to the patient are thus absolutely essential, and although antigen tests are easy to use and were indispensable during the peak of the COVID 19 pandemic, they still lacked the desired accuracy compared to hospital-based PCR tests. In the Ultrazyme project, we want to develop an enzyme tailored for use in molecular-based self-tests, but with the accuracy of PCR-based tests. Since the enzyme works well at room temperature, sophisticated equipment is not required. By succeeding in this project, UltraZyme can offer the enzymatic solution for a rapid and cost-effective test for disease identification and monitoring. A key element is that the test can be carried out without the use of trained personnel or own equipment.",,2025,"UNIVERSITETET I TROMSØ - NORGES ARKTISKE UNIVERSITET, FAKULTET FOR NATURVITENSKAP OG TEKNOLOGI",506208.61,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2023 +P29106,341898,Early Digital Decisions for General Practice Excellence,"A public health crisis is increasing numbers of children and adolescents with mental health disorders and need for services. In 2021, ~65,000 children and adolescents received Norwegian Child and Adolescent Mental Health Services (CAMHS), a 14% increase over the previous year. While some increases are attributed to COVID-19, increasing prevalence began earlier, likely correlated with factors, including social media and climate change. Concurrently, there is a specialist mental health service provider shortage, leaving the burden to already overstretching general practitioners (GPs). This situation is not sustainable. EDDGE is designed to create ""more for the same."" Using the CAMHS model, EDDGE changes health system processes to increase effectiveness and efficiency in primary and specialty care. EDDGE brings digital and decentralized tools for clinical decision-making to GPs. These tools include ready access to evidence-based practice guidelines and community practice standards, derived from local health data, to optimize GP management of child and adolescent mental disorders and facilitate appropriate CAMHS referrals. The change process provides similar support for CAMHS, including guidelines and local health data to optimize practice, while providing guidelines for referral acceptance and returning care to GP's. This will promote cooperation between primary care and CAMHS services and create a robust and sustainable system for providing comprehensive mental health services for children, adolescents, and their families. Properly implemented, EDDGE serves as a model for other segments of the healthcare system by optimizing services for patients, citizens, and public health services. EDDGE strengthens new and existing clinical care through collaborations in the public and business sectors. Service users will be engaged in the design, evaluation, and implementation of EDDGE structures and processes, in collaboration with others involved in project development.",,,NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU,7393.6,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Digital Health,,,Norway,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2023 +P29109,333857,The AEGIS Dual Purpose Helmet - Surgical helmet and efficient respiratory protection in one device!,"The WHO estimates that up to 180,000 health workers died before May 2021 from Covid-19. We combine the advantages of face masks, motorized respiratory protection and surgical helmets in an innovative helmet, tailored for the healthcare industry. The AEGIS helmet can be used as a surgical helmet during orthopedic operations and easily converted into a highly effective respiratory protection for healthcare personnel. The helmet protects against viruses, bacteria and other harmful particles - several hundred times better compared to FFP / N95 masks which do not fit all users. Unlike motorized respirators, disinfection is simple as the helmet is covered by a disposable cap while an adapter is hand disinfected. In an emergency situation, hospital personnel can easily convert used equipment into effective infection control equipment. The COVID-19 pandemic revealed a lack of preparedness of infection control equipment in Norway. However, even if available, masks and FFP / N95 often do not provide sufficient protection and are often experienced as uncomfortable during prolonged use. At AHUS, a team of orthopedists, engineers and filter experts have therefore developed a filter solution, which converts surgical helmets, which are normally used during orthopedic operations, into safe infection prevention helmets. FFI has tested the ""EURODAPTER"" and found that it provides several hundred times better protection compared to FFP masks. It is comfortable to use, the patient can see the user's face and it is easy and quick to disinfect with little storage space. All findings have been published, the invention is patent pending. We have produced a series, which is in use in the operating, intensive care and medical monitoring departments at AHUS under emergency certification. The aim of this project is the development of a new type of surgical helmet with a built-in filter function, the AEGIS helmet in collaboration with an established engineering and design agency. After the development and certification phase, a strong sales team will bring the product to market. As far as we know, there are no similar surgical helmets with a filter function on the market today.",,2024,ORTHECTA AS,559150,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Hospital personnel,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2022 +P29111,326461,Long-term effects of SARS-CoV-2 infection: An interdisciplinary observational and interventional study program,"COVID-19 has been associated with adverse long-term health effects. Acute lung injury can be followed by chronically reduced lung function. COVID-19 may also be associated with an increased risk of chronic damage to the cardiovascular system. Persistent heavy breathing can be a symptom of both heart and lung damage. Infection with the SARS-CoV-2 virus can also directly or indirectly lead to damage to the central nervous system. The studies that have provided evidence that COVID-19 is associated with an increased risk of chronic lung, heart or brain damage have largely been based on patients who have been admitted to hospital. Most of these study patients have lacked detailed information about their state of health before they were affected by COVID-19. This makes it difficult to know whether it is COVID-19 or another illness that the patients had before COVID-19 that contributes most to the disease observations that are made. Health information about patients with COVID-19 from the general population who have not been hospitalized is limited. In order to more reliably determine the long-term effects of COVID-19 on the heart, lungs and central nervous system, we will study not only patients who have been hospitalized, but also people in the general population who have tested positive for SARS-CoV-2 and who have previously have been examined with extensive tests of lung, heart and brain function. Given that COVID-19 is a new disease, there are limited data on how long-term effects can best be treated. We will therefore test the effect of possible forms of treatment that have different attack points.",,2026,"UNIVERSITETET I OSLO, DET MEDISINSKE FAKULTET, Institutt for klinisk medisin",1408296.4,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P29112,322672,Biobank Norway 4 - a national biobank research infrastructure,"As a national research infrastructure, Biobank Norway (BN1 2011-15, BN2 2016-20, BN3 2020-24) has been central to the establishment of a modern and advanced nationwide biobank network at all partner institutions and has fulfilled a key requirement for promoting outstanding research. Biobank Norge 4 will gradually be further developed to: i) meet new and urgent needs related to a new national data landscape, previously led by the Directorate for e-Health (NDE), now FHI and the Directorate of Health, ii) lay the foundation for promoting personalized medicine, and iii) develop the biobank network to meet data-critical, analytical challenges that arose during the COVID-19 pandemic with great relevance to national preparedness in general. Due to legal challenges with data sharing in a cloud solution, the development HAP was stopped, but BN is heavily involved in an alternative solution developed by the universities based on TSD (UiO), HUNT Cloud (NTNU) and SAFE (UiB). BN is working on a way in for access to all biobanks, a solution that will be integrated with Helsedataservice and their researcher portal for access to register data. To achieve our goals, BN4 also collaborates with national and European ""sister infrastructures"", including other Research Council-funded infrastructures such as ELIXIR, NorCRIN, NSC (Norwegian Sequencing Center) and BioMedData. BN4 will support the ongoing work at helsenorge.no to facilitate a digital dialogue with research participants and biobank donors. This synergy will optimize the use of the significant infrastructure investments that have already been made by utilizing the expertise and knowledge of partner infrastructures. BN4 also involves a merger with MoBa's infrastructure application (iMoBa). This joint initiative significantly strengthens BN4 in several areas, i.a. through a uniform and strategically coherent plan for the development of good digital administrative solutions, including data banks for returning analysis results which can in turn be used by all researchers upon application. We contribute to the further development of metadata and visualization tools for large genetic databases, and the compilation of a FAIR-compatible, harmonized genotype data set across cohorts, an important contribution in the field of personalized medicine. BN has also started a structured research collaboration with industrial players, i.a. with a start-up company partially supported by the Research Council. BN is heavily involved in the European research infrastructure for biobanks, BBMRI-ERIC and leads through NTNU, in collaboration with BBMRI-ERIC, a recently started (01.01.2024) EU project to develop a new concept for a European research infrastructure for large medical cohorts (INTEGRATE LMedC).",,2031,NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU,11266371.2,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Health Systems Research,"Medicines, vaccines & other technologies | Health information systems",2022 +P29115,337454,"The pandemic center national conference 2022: ""Pandemic, diversity and social inequality""","Over two years under the auspices of COVID-19 has taught us that pandemics occur regularly and represent major societal challenges that must be met in a sustainable way and with a knowledge base from all disciplines and good cooperation between academia, public institutions, business, volunteering and politicians. COVID-19 has also made visible and reinforced social inequalities in health and in the use of health services. Finding good solutions in the areas of interaction between these two societal challenges, pandemics and inequalities, can be an important key to better preparedness for the next pandemics. During the pandemic, the authorities lacked knowledge-based evidence as a basis for important decisions that could have unforeseen consequences. Coordination between agencies and services has improved in the last two years, but there is still potential for improvement. More and better collaboration between the disciplines is also necessary in the future to tackle such challenges. The over-representation of vulnerable groups such as immigrants, but also involvement in civil society during the pandemic also points to the fact that we need to include more actors in the best solutions. The diversity in society should be utilized for a better understanding of the importance of social inequality, how it affects health and quality of life and how best to improve preparedness before the next pandemic occurs. The academic environments, health and welfare services, civil society, business and users lack arenas for the exchange of experiences and joint reflection on good solutions now that the pandemic has hopefully calmed down. That is why we want to organize a national conference under the title ""Pandemic, diversity and social inequality"" where relevant professional fields and social actors meet to work towards better future pandemic preparedness and good health for all.",,2023,"UNIVERSITETET I BERGEN, DET MEDISINSKE FAKULTET",20279.47,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience",,2022 +P29116,334195,LTX-109 as a therapeutic and prophylactic agent for upper respiratory tract infections,"The SARS-CoV-2 pandemic is expected to become endemic in the coming years with occasional flare-ups. In particular, the continual emergence of new coronavirus variants, some of which may be resistant to current vaccines, pose a risk. It is therefore expected that the need for new safe and effective treatments for COVID-19 patients will persist. Hence, as part of an overall COVID strategy, new effective broad-spectrum antiviral medicines need to be developed as complementary therapies to vaccines. LTX-109, as an intranasal antiviral for use in an outpatient setting, may represent an attractive treatment option for battling the pandemic. LTX-109 is a novel short cationic synthetic peptide-like molecule/peptidomimetic (monocarboxylic acid amide, tripeptide, with molecular weight of 897.46 Da) which binds preferentially to negatively charged membrane components on microorganisms via electrostatic interactions, subsequently inducing fast-acting membrane lysis and death/inactivation. LTX-109 has recently been found to have a virucidal effect on SARS-CoV-2 and other viruses, including Influenza A. LTX-109 is also in development for antibacterial use for the indication Nasal Decolonization of S. aureus, among others. LTX-109 is not approved for marketing in any indication. LTX-109 has been found safe in five clinical trials and efficacy data are compelling on bacteria and fungi, and, albeit only in vitro (while awaiting results from the ongoing Proof-of-Concept clinical trial), on several viruses, including SARS- CoV-2.",,,PHARMA HOLDINGS AS,11266.37,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Clinical trials for disease management | Prophylactic use of treatments",2022 +P29117,333246,QUAL: Design of long-acting SARS-COV-2 neutralizing antibodies,"The elderly and people with weakened immune systems do not necessarily respond effectively to vaccines. There is therefore an urgent need for specific treatment that prevents the development of severe COVID-19. Development of monoclonal antibodies that specifically target the virus followed by blocking of infection and elimination from the body is an attractive strategy for both therapy and preventive treatment. This is supported by recent clinical data. However, antibody treatment is expensive and unfortunately not necessarily available to those in need on a global scale. As such, in collaboration with international non-profit organizations, we have isolated fully human monoclonal antibodies that effectively block all relevant SARS-CoV-2 strains of concern. The antibodies bind to independent and conserved binding sites on the spike protein, and can therefore be given as a cocktail. However, uptake and availability of such monoclonal antibodies has been extremely limited due to high doses required and intravenous formulations. In this project, we have tested a unique antibody technology, patented and developed by us, to investigate whether the technology can be used to extend the plasma half-life and improve the distribution of IgG1 monoclonal antibodies directed against SARS-CoV-2. The results show that the monoclonal antibodies combined with the technology can be produced as efficiently as the parental antibodies. Furthermore, we show that the technology provides significantly extended duration of action in a humanized mouse model under optimal conditions that are predictive of pharmacokinetics in a human setting. The very good data now motivates verification of the technology in non-human monkeys.",,,OSLO UNIVERSITETSSYKEHUS HF,56331.86,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P29118,324668,"Epidemic traces. Remains of infectious disease control in Africa, and how they shape future health.","Epidemics such as Covid-19 are experienced as events, which suddenly come and disappear again. But epidemics - and measures against them - leave permanent traces. For example, we live with cemeteries, hygiene rules and water supplies, which came about during the 19th century cholera epidemics; tropical diseases were fought after the war with persistent landscape changes and with insecticides, which are still found in soil, water and bodies; the large global vaccination campaigns against childhood diseases in the 70s built new routines and technologies; 2000s HIV programs created new hospitals and collective activist groups, which continued after the AIDS epidemic; and Covid-19 will leave, among other things, new digital control technologies and legislation. These tracks have effects, long after they were created. Infrastructure or medicine against a disease can be reused against new health problems; but epidemic traces can also create new diseases, if e.g. medicines lose their effectiveness or increase susceptibility to new diseases, when insecticides cause cancer, or when bad experiences with disease control leave persistent distrust of health institutions. In other words, epidemics overlap and interact over time, through their persistent tracks. EpiTraces combines social anthropology - which studies human life, relationships and institutions in the present - and medical history - which uses archives and oral testimony - to pursue how the traces of epidemics and disease control in Africa throughout the 20th century affect disease and health today and in the future. We will follow the tracks of exemplary epidemics such as sleeping sickness, malaria and river blindness, HIV, Ebola and Covid, in the present, and their diverse social, medical, political-economic and ecological effects. With this, the project contributes to a more nuanced picture of ongoing epidemics, such as Covid-19, cancer or diabetes, which will also benefit preventive strategies against them.",,2027,"UNIVERSITETET I OSLO, DET SAMFUNNSVITENSKAPELIGE FAKULTET, Sosialantropologisk institutt",1387038.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Ebola virus disease | Other,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts | Other secondary impacts,2021 +P29119,326210,Disinformation and people: Impacts on societal trust and resilience,"Have you ever read stories about 5G cell towers spreading COVID 19? Or that the EU supports mass illegal immigration? If you've ever read a post on social media that seems to fish for a strong emotional response, especially fear, there's a good chance it was misinformation or disinformation or fake news. People like you and me have become a target where someone wants to give us strong emotional reactions - from curiosity to disgust or fear - either to make money from the number of clicks or to use fear to increase our doubts about our own authorities and what we normally would consider as reliable sources of information. Our potential distrust of our authorities and/or our neighbors can contribute to social instability, especially during a crisis. The FAKENEWS project focuses on what people do in crises, especially in light of increased misinformation and disinformation that can be used to mislead people, increase mistrust of authorities or others and worsen a crisis situation. We ask: How do civilians' perceptions of threat and subsequent actions affect society's trust and resilience in the face of crises? Norway and Sweden are both known as societies with a high level of trust. However, Sweden and Norway do not handle crises in the same way. FAKENEWS examines the Norwegian and Swedish responses to two crises: the COVID-19 pandemic and the migration crisis of 2015, and how trust and resilience (our ability to resist or adapt to changes due to crisis) were affected during these two crises. We are particularly interested in the effects of error and disinformation on societal trust and resilience. The data collected will be used to compare institutional policies and legal measures, with how people themselves felt and reacted to these crises. Research results from our data analysis, scenario development and exercises will be shared openly via social media, seminars and with decision makers to contribute to academic and public debates.",,2026,UNIVERSITETET I TROMSØ - NORGES ARKTISKE UNIVERSITET,1359413.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience",Communication,2021 +P29120,328920,Simulation as a pedagogical method in a lifelong learning perspective.,"After a long period of distance and home office for part of the sector and increased activity and restructuring of activities for another part of the sector, it will be useful to have a foot on the ground now. We need both to look back at the experiences we have gained within the education and health sectors when it comes to changing studies and practice during the COVID pandemic, and look ahead to discuss how we can use these experiences in the future. We have seen how nursing education has had to change, shift or shorten practice courses and how the health services have had to turn around and adapt their operations to new realities that came with the pandemic. How did we do this? What role did or could simulation training play in such a situation? What experiences have you gained that we can share, learn from and take with us further? We want to discuss in more detail how simulation can function as a tool for skill enhancement and lifelong learning both in an extraordinary situation and in a longer perspective with more ordinary operations. The pandemic experiences have again shown how important it is to work cross-functionally, carry out mass training and practice for unforeseen situations. Can we work even more systematically with this in collaboration between education and the health sector, and at the same time take a step further where the theory-practice gap is illuminated from both the education side and the practice side?",,2022,"VID VITENSKAPELIGE HØGSKOLE AS, VID HARALDSPLASS",14101.56,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P29124,326136,Crisis Management in a Polycentric Nordic Local Democracy: Different Governance Structures - Different Results?,"The Nordic municipalities are important for handling crises in society. The strategies may be adopted centrally, but they are implemented locally. The POLYGOV project is a comparative study of crisis management, organization and the functioning of the local democracies in Iceland, Norway, Sweden, Finland and Denmark with a background in the different handling of the COVID-19 pandemic. The thesis that guides the project is that the countries' institutional choices with regard to local and regional governance are important factors in understanding their ability to organize, coordinate and manage the COVID-19 pandemic. The project compares the local and regional coordination and management strategies used as the pandemic unfolded from March 2020 to date, including vaccination strategies. The unique thing about the project is that it utilizes the exceptional learning potential that lies in a comparative analysis of institutional data and data on actual crisis behavior in the Nordic governance systems. The overall aim is to identify the differences in the Nordic countries' handling of the pandemic, the results thereof, and to link these differences to public policy, governance, organization and management. The outcome variables include local inequality in health (disease, death and vaccination) and social security (economic and social measures). The research team consists of researchers from nine Nordic universities in the five Nordic countries, including the Faroe Islands, Greenland and Åland. The handling of the pandemic is studied through four perspectives: legal, public health, governance and organisation. The empirical basis is Nordic legal sources, several quantitative data collections (surveys and register data) as well as strategic case studies. The project will provide knowledge on how to properly maintain and further develop sustainable democratic local and regional governance in crises.",,2024,OSLOMET - STORBYUNIVERSITETET,1386576.14,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts | Social impacts,2021 +P29125,327917,Nanoparticle-based diagnostic solutions,"Lybe Scientific is a newly established biotechnology company within diagnostics and is based on interdisciplinary research at NTNU. Lybe Scientific's first product is a diagnostic solution currently used for COVID-19 diagnostics with approximately 6.2 million units sold domestically and internationally during the pandemic. This solution has been prepared from two strong professional environments within molecular biology and chemical engineering. With a basis in the underlying technology, Lyb Scientific's opportunity is to continue to further develop this platform technology, and the vision is to be a leading supplier of cost-effective products for a wide range of life science and diagnostic purposes. This project seeks to cover Lybe Scientific's need for R&D activities around new functionalized nanoparticles for RNA and DNA applications in a selection of biological sample materials. The main goal is to expand the product portfolio of solutions for different clinical application areas and establish efficient production processes for these products.",,2024,LYBE SCIENTIFIC AS,1682708.86,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P29134,315957,The Ethics of Contagion: How We Should Respond to the Spread of Infectious Diseases,"The SARS outbreak of 2002-2004, the swine flu pandemic of 2009-10 and the Ebola epidemic of 2014-2016 were all stark warnings of what was to come. Yet the COVID-19 pandemic took most governments to bed. The pandemic not only revealed a lack of pandemic preparedness, but also a number of unresolved ethical problems: What restrictions are the authorities justified in imposing on citizens to protect public health? How should we distribute the burdens of fighting the disease within the population? What role should markets play in distributing scarce goods in times of crisis? To combat the spread of infectious diseases, populations in many countries have lived with highly invasive measures. The measures are often justified with regard to public health, but can we also justify the measures to those who bear the heaviest burdens? If we are to answer this question, we need an understanding of what moral obligations we have to prevent the spread of infectious diseases. I want to build a framework for how governments can respond to the spread of infectious diseases which is based on our individual moral obligations and which can thus be justified towards those affected by the measures. I present three overarching hypotheses: The first is that individuals have more demanding obligations to prevent the spread of disease than theories of moral responsibility suggest. The second hypothesis is that the highly invasive measures to prevent the spread of infection can be justified as payments for participating in a social insurance scheme. The third is that we need a new understanding of when we are justified in using market mechanisms in a pandemic, such as e.g. in the production and distribution of vaccines. My overall goal is to contribute to the further development of ethical thinking around infectious diseases and to point out a way forward that transcends professional boundaries and that can be accepted by people with different ethical starting points.",,2024,"OSLOMET - STORBYUNIVERSITETET, FAKULTET FOR HELSEFAG, Institutt for sykepleie og helsefremmende arbeid",449400.47,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in the Allocation of Resources | Research to inform ethical issues in Governance,2021 +P29135,327856,Clinical testing program for use of LTX-109 as treatment against COVID-19 infection.,"In 2020, Pharma Holdings has conducted an in vitro study to determine the effect of LTX-109 on three enveloped viruses, one being the SARS-CoV-2 virus. The results are compelling and confirm that LTX-109 exerts a virucidal effect against the SARS-CoV-2 virus. Pharma Holdings believes that the in vitro results of LTX-109 on SARS-CoV-2 demonstrate a high potential and a need for clinical translation, and that LTX-109 (preferably, in a gel form) may turn out to be a valuable treatment for COVID-19, and similar respiratory virus infections. Pharma Holdings is conducting a Phase IIa, double-blind, placebo-controlled, interventional parallel group study to evaluate the antiviral effect of a single nasal application of LTX-109 3% gel, in comparison to placebo gel, in subjects with COVID-19 infection. The study is approved by the Swedish Medical Products Agency and is scheduled to start recruiting patients on April 20. In this proposed EU project application, Pharma Holdings aims at demonstrating and validating the clinical efficacy and safety of LTX-109 gel as an innovative anti-viral agent for treatment of SARS-CoV-2 infections in the upper respiratory tract in Phase II / Phase III clinical programme.",,,PHARMA HOLDINGS AS,46234.62,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II | Clinical Trial, Phase III",Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Phase 3 clinical trial,2021 +P29136,322415,H-work dissemination and learning platform,"H-work dissemination and learning platform (e-H-work) Mental health challenges are a growing social problem in general, but also in working life in particular. ¼ of the EU's working population is expected to experience mental health problems during their lifetime (e.g. symptoms of depression, anxiety, stress and burnout). Many small and medium-sized businesses lack both training, resources and knowledge on how to manage employees' mental health and well-being, and take action. The strengthening project e-H-work intends to develop a dissemination and learning platform to convey and practically benefit from the results of the Horizon 2020 project H-WORK https://h-work.eu/ The target group is mainly managers and HR personnel in small and medium-sized companies and public sector who plan to promote mental health and well-being at their own company and who want to carry out this process yourself. Three learning videos and three instructional videos are planned for how to make simple moves for best practice. All learning material will be collected in a flexible online course through the development of an e-learning course on how to systematically promote mental health and well-being in your own company, which is free and available to everyone. The parent project H-work consists of an interdisciplinary team with various experts and practitioners from 9 different countries who will all contribute with their unique expertise to the development of the communication and learning platform. Through digital education and training in the use of the tools prepared in H-WORK, it will be possible to ensure a wider and more efficient utilization of H-WORK's results. Digital courses and training are especially important in light of COVID-19, which has not only increased the likelihood of mental disorders, but also the need for digital solutions. In Norway, we have a large public sector and many small and medium-sized companies that do not necessarily have the financial resources to use either internal resources or hire consultants to work with psychosocial work environments and mental health. Then courses, as well as learning videos and instructional videos will be of cost-effective and sustainable help so that the organizations can work on this on their own. In the short term, this will give managers and organisations better understanding of good tools that can help make it easier to work with, include and retain employees who have mental health problems. In the long term, this will prevent stress, burnout and mental disorders, and thereby reduce sickness absence, saving society a great deal health costs and thus have a socio-economic benefit. Knowledge of mental health will help to reduce stigma and create more transparency around mental health. This will make it easier for individuals to meet understanding and seek help.",,2024,"NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU, NTNU FAKULTET FOR SAMFUNNS OG UTDANNINGSVITENSKAP, Institutt for psykologi",115586.54,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2021 +P29137,323383,115025 Pathobody: A proteogenomic pipeline for capture and sequencing and production of pathogen-specific antibodies,"AbSano has changed the patient criteria for inclusion in the study so that we now include patients who have had COVID and have additionally taken a vaccine. We have seen that this gives the highest number of B cells in the FACS sample. AbSano has generated and tested the TSN (concentration) for the B-cell selection, as well as defined conditions for labeling by FACS. Absano has also tested and defined the conditions for the B-cell cultures, conditions which have now been put into use. ELISA analyses, which test for: antibody production, antibody specificity and neutralization capacity, are now done for each individual B-cell culture. GenXPro has worked on the development of sequencing protocols for antigen-binding fragments from antibodies. They have developed and tested preparation protocols for the NGS library. This was done in two steps, first the experiments were designed and developed, and then this knowledge was used to analyze the test sequences. Erasmus MC has received ~2000 FACS selected B cells for 10x Genomics sequencing. Sequencing is still ongoing. Erasmus MC has also worked on the validation of the affinity enrichment from supernatants from the B-cell samples. They have carried out a successful affinity enrichment where they were able to identify immunoglobulin-related peptides via proteomics analysis. They were able to show that proteomics data could be matched with available NGS data from the reference culture, thus confirming a good workflow. Pubgene has carried out a literature analysis for current COVID antibodies, their status with regard to clinical studies, target sequence for the antibodies, scientific findings and patent situation. PubGene has also developed methods and routines that allow monitoring of scientific progress within the field. Pubgene has started work on database design and framework for storage, mapping and analysis of the various data elements that are expected from the various analyzes from the various experiments. This gives us a good basis for data handling, storage and analysis of future data from the project",,2024,PUBGENE AS,681729.42,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Pathogen genomics, mutations and adaptations | Immunity | Health service delivery",2021 +P29138,328394,OPN-019 for COVID-19: early intervention to reduce viral transmission and disease progression.,"Through the EU project, we will primarily deliver results of two clinical phase 2 trials, each with 400 patients/subjects recruited. The first study will be for therapeutic efficacy and safety of OPN-019 (two dosages versus placebo for 14 days) in adult patients with COVID-19 either with mild illness (no oxygen required) or who are asymptomatic/presymptomatic, and eligible patients must have at least one additional risk factor such as >65 years of age, on treatment for hypertension and/or for diabetes type 2, have BMI >30 or be immunosuppressed. The second study will investigate the efficacy and safety of OPN-019 (two dosages vs placebo) as prophylaxis against developing detectable infection in adult subjects who are negative for SARS-CoV-2 virus but who are at risk for infection due to cohabitation contact with a known-positive subject. Another work package will be devoted to regulatory agency liaison; specifically to obtain scientific advice and negotiate agreement for the clinical development plan with the European Medicines Agency (EMA). Likewise, we will present and agree the study protocol to national agencies in the EU/EEA countries in which we will run the two clinical trials. A 4th work package will involve manufacturing upscale development for cGMP production for later phase 3 studies and commercial sales. In order to reduce overall risks, we plan to have both a European as well as an American manufacturing site so that sufficient quantities of the drug&device combination can be ascertained even for peak needs.",,,OPTINOSE AS,43344.95,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Individuals with multimorbidity,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Prophylactic use of treatments,2021 +P29142,315624,"Coordination, Response and Networked Resilience","The word ""crisis"" is usually used for dramatic events that occur suddenly, such as major accidents, natural disasters or terrorist attacks. Although such events can have catastrophic consequences, they are usually confined to a specific location and last for a short period of time. The COVID-19 pandemic has been something else entirely - a creeping crisis with an unclear beginning and end. The starting point for CORNER was that effective handling of a pandemic is created at the intersection between political-administrative leadership on the one hand, and reactions and responses from the population on the other. This means that the project has two main tracks - the authorities' management exercise, and how the situation and decisions are interpreted by the population. In the first main track, we have studied management at national, regional and local level in Norway, Sweden and Italy. The starting point for all the countries was a serious lack of basic infection control equipment and supply chains with such a small degree of buffer that there was a shortage of absolutely essential input factors. This was an important context for management and adaptability in the pandemic. In Norway, we have had the opportunity to observe management practices from the inside, while the crisis was going on. We have seen management and decision-making that have at times been characterized by extreme uncertainty in the knowledge base, particularly in those periods where new mutations created reason to ask questions about contagiousness and mortality. Situations with a combination of low infection rates, fatigue and the need for new precautionary measures created demanding dilemmas for management and risk communication. In the data material we naturally find examples of coordination problems, misunderstandings, conflicts, challenges in prioritizing operational and strategic tasks and, not least, frustration over a lack of personnel and infection control equipment. Anything else would be surprising, given the complexity of the situation and the organizational landscape in which it has been handled. The data material is just as much characterized by examples of collaboration and adaptability at local level. We have observed new structures for cooperatives which relatively quickly filled structural gaps between sectors, but which were not always as closely linked to the contingency planning that had been done in advance. We have seen collaborative structures that existed for completely different purposes than crisis management, but were reconfigured during the pandemic. We have seen the emergence of completely new organizational and technical solutions that were essential to adapt to the ever-changing challenges that emerged during the pandemic. In this sense, the crisis has provided invaluable lessons about an ability to adapt that could hardly have been imagined in advance. The preliminary conclusion is that the biggest difference between the three countries lies at the national level. At national level, in March 2020, a decision dilemma was faced between speed and precision in the introduction of measures. Where Norway prioritized speed through a precautionary principle, Sweden chose a strategy based on precision and expertise. This is linked to differences in regulatory and administrative systems, but can also be seen as more cultural differences in ""policy style"" and institutional logic. Italy's response was characterized by the fact that they were the first epicenter in Europe and thus had less time to compensate for shortcomings in preparedness. The Italian response has been described by other researchers as initially characterized by denial, weak central management capacity and a complex regional structure (Capaldi 2020). The response was eventually strongly characterized by an expertise orientation, where a small selection of medical experts was given very large decision-making authority. All the countries' choice of strategy appears to be as much a result of historical conditions and administrative tradition as an analytically chosen strategy. The second main track in CORNER has been to understand how the population in Norway, Sweden and Italy interpret the seriousness of the situation and the proportionality of the measures decided upon. The starting point for this part of the analysis was that large amounts of text have been produced on social media throughout the pandemic, and that this can tell something important about the social construction of risk and legitimacy. By studying large amounts of information from social media, we have gained an insight into people's interpretation and negotiation around legitimacy, proportionality, moral positions in the relationship between individual and collective action, as well as various authorities' risk communication. We find particularly important information in the controversies that arose around measures that approached a limit for what was considered proportionate and democratically acceptable, for example the face mask mandate. In addition, these analyzes have provided the opportunity to study changes in discourses over time. The project runs until 2024 and results from the analyzes are published continuously.",,2024,NTNU SAMFUNNSFORSKNING AS,1387038.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Impact/ effectiveness of control measures | Communication,2021 +P29145,321413,CANARY - MicroNano biosensor for continuous vital sign monitoring,"In the CANARY project, Sensocure is working to develop a unique new product, a sensor-based early warning system that will continuously monitor for systemic increases in carbon dioxide (CO2) in the body, which indicates a critical condition for the patient. Examples where our system will be able to provide unique, important and reliable information about the patient's systemic health are: potentially life-threatening conditions such as sepsis, acute blood loss and heart failure, or critical worsening of serious chronic or acute respiratory diseases such as COPD (chronic obstructive pulmonary disease) or COVID-19 . For these patients, early diagnosis and treatment, as a result of pCO2 monitoring, can dramatically improve prognosis and save many lives. In the first project year, Sensocure has worked on the design and modeling of a sensor container adapted to the application, i.e. for non-invasive use (without penetration of skin or cell boundaries). We investigate sensor mounts and contact materials, with a particular interest in flexible, biocompatible and medically approved polymer materials. We have developed a first prototype for the control electronics, and have tested it together with pCO2 and SpO2 sensors, in the laboratory and on healthy volunteers, with promising results. It is a portable system, with a battery-powered control unit and Bluetooth transmission of measurement data to a PC. We are working with a new concept for calibrating the pCO2 sensor, in air, which will enable a faster, simpler and cheaper calibration process. We have started the development of a new pCO2 sensor. We research new materials and configurations for electrodes and membranes, with simulations and tests in the laboratory. Sensocure collaborates with SINTEF Digital, department for smart sensor systems and with Oslo University Hospital, at Medical Technical Operations (OUS MTV). A significant national and international network of partners and subcontractors will be used.",,2024,SENSOCURE AS,1402295.91,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Innovation,,,Norway,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P29146,323019,Top Funding: Political Dynamics of Slow-Onset Disasters - Contrasting Antimicrobial Resistance (AMR) and Ebola Responses,"Disasters differ markedly in their speed and pattern of manifestation, which in turn greatly affects how researchers as well as authorities interpret and respond to them. While theoretical innovations made by disaster researchers over the last century have almost exclusively been developed for the study of large rapid-onset disasters, disaster assessments reveal that elusive and slow-onset disasters affect more people on aggregate. I recently carried out a preliminary study suggesting that slow-onset disasters have primarily been addressed as something 'other' than conventional disasters, and have fallen outside the scope of most disaster studies. We therefore lack theoretical frameworks capable of describing the policy dynamics of slow-onset disasters, largely because existing studies focus on individual slow-onset hazards (e.g. climate change, pandemics or droughts). In this project, I will address this gap by studying the ways in which two types of slow-onset disasters vary through a political response and health policy lens. By contrasting the political response trajectories of antimicrobial resistance (AMR) and Ebola I will investigate how incremental slow-onset disasters (such as AMR) differ from cyclical ones (such as Ebola) with implications for policy response. The project will be hosted at Roskilde University (RUC), Denmark. Empirically, the project employs a health sector focus where the global- and EU-level political response to AMR is juxtaposed with the Ebola response using process tracing analysis. This provides both novel insight on how an incremental slow-onset disaster (AMR) differs from a cyclical one (Ebola), as well as new knowledge on the dynamics of AMR and pandemic policymaking. The overarching puzzle and ambition of the action is therefore to understand how different slow-onset disasters vary and which implications this variation has for precautionary planning and policy.",,2022,Ukjent Organisasjon,49124.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Research Council of Norway (RCN),Norway,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Policy research and interventions,2021 +P29148,321622,Second generation COVID-19 vaccine on the Vaccibody platform,"Since December 2019, the SARS-CoV-2 coronavirus has caused over 770 million cases and over 7 million deaths. At the start of the epidemic, there was a great need for vaccines that could prevent infection, serious illness or death. Nykode Therapeutics ASA (formerly Vaccibody AS) had previously developed a DNA-based vaccine technology that targets antigens to antigen-presenting cells in the body to provide a stronger and faster immune response, and before the epidemic had developed two cancer vaccine candidates based on this platform. In 2020, Nykode set itself the goal of developing a competitive second-generation preventive vaccine against COVID-19, and designing this based on our advanced bioinformatics analyzes and molecular design. Several candidates were designed and evaluated experimentally, and these were shown to stimulate rapid and sustained functional antibodies and appropriate T-cell responses in animals. The candidate that was selected for clinical testing is based on the Spike protein from the South African virus variant B.1.351 after promising data in mice. VB10.2129 was then produced under ""good manufacturing practice"" (GMP), and a clinical trial with this vaccine was carried out in Norway in the period 2021-22. This was a dose-escalation study among healthy adult volunteers, and the main objective of the study was to investigate the safety, secondly the immune response generated by the vaccine (NCT05069623). This project has contributed to developing and evaluating a new COVID-19 candidate and at the same time generating new inventions, and created valuable data in humans for use of the technology platform from Nykode.",,2024,NYKODE THERAPEUTICS ASA,1697157.18,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine design and administration,2021 +P29153,320851,"The COVID 19 pandemic - risk factors, severity, and the consequences of nationwide control measures on public health","In this project, we want to study the clinical effect of the COVID19 pandemic, as well as the consequences of national infection control measures at various levels in close collaboration with Trøndelag county municipality, Frosta municipality, Trondheim municipality and FHI. The largest population-based, prospective health survey in Norway, the HUNT study, has already been conducted four times in Trøndelag in the period 1984-2019. Based on the latest HUNT 4 study (2017-2019), with 60% attendance in Frosta municipality, and 54% among all invited, we have an excellent base of health data and biological markers collected just before the SAR-CoV2 virus was detected in Norway to study both the biological, economic and social consequences of the pandemic and the effect of different degrees of lockdown. We will build on an already established collaboration with the public health service at county and municipal level. We will study i) general health and well-being ii) short and long-term effects of COVID19, iii) total and cause-specific mortality and possible changes in the development of other diseases, iv) significance for mental health and effects of socio-economic positioning, v) whether we can demonstrate special consequences for young people and the elderly, vi) a clinical survey of infected people in the population and a follow-up of vaccination response and possible special side effects based on the same cohort. The study started on 1.9.2021, 5,000 have so far been included with an attendance of 63% of those invited",,2024,"NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU, NTNU SENTRALADMINISTRASJONEN",1849384.65,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Clinical characterisation and management | Infection prevention and control | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Restriction measures to prevent secondary transmission in communities | Adverse events associated with immunization | Characterisation of vaccine-induced immunity | Indirect health impacts | Social impacts,2021 +P29155,314318,"Innovation, consumer understanding and food processing knowledge for increased sustainability and health","WP1 Sustainable Food Innovation: Our focus is to improve innovation in companies and build the bridge between research and industry. We study both large and small companies, and examine how sustainability practices are integrated into established Norwegian food companies. The findings show an increasing adaptation between sustainability and innovation strategies, promoting collaboration and new business models. Innovations in products, processes and organization support the sustainability work and require new skills related to sustainability. We examine the entrepreneurial orientation and innovativeness of local food producers and evaluate their ability to learn from competition and explore new markets. Our goal is to facilitate the transition to sustainable innovations in established companies and promote innovative initiatives for small and medium-sized food producers. During the COVID-19 crisis, we utilized the Future Food network to create innovative solutions, strengthen collaboration and develop concrete projects to increase competitiveness. We also investigated sustainable business models and value chains in the bioeconomy and for plant-based food companies. To facilitate the transfer of knowledge, we developed methods to make research results available to the food industry with a focus on consumer-oriented product development. Design-based innovation, workshops and visualization tools were essential to transform research into practical results. Prototyping supported interdisciplinary collaboration and improved understanding and communication across disciplines. WP2 Consumer and Sensory: Our research in healthy eating examines the relationship between taste sensitivity, oral microbiota and preferences to understand their potential links with overeating and unhealthy eating habits. We discovered that taste sensitivity in children and young people affects their food choices. We assessed tactile sensitivity using various instruments and model samples, and explored the possibility of personalized, healthier food products. To understand the way food is eaten, we developed Face Scanner software (Food Behavior module) to analyze chewing and swallowing patterns in relation to food texture, helping the industry formulate food with specific textures that people like while reducing overeating. We investigated sensory barriers (taste and texture) in connection with healthier and more sustainable diets, and called for increased consumption of plant-based foods and the use of the whole animal, including residual raw material, in sustainable and innovative foods. Positive experiences with plant-based meals in school influenced pupils' attitudes towards vegetarian food. We also worked to reduce food waste in households through intervention studies with young consumers, with a focus on specific consumer groups and promoted methodological aspects of sensory and consumer research as well as associated statistical methods. We used co-creation methods with young people both in workshops and on an online platform, where the ideas generated for new products were evaluated by selected industry stakeholders, and emphasized the value of co-creative approaches for the Norwegian food industry. WP3 Food technology: Studies linking the quality of wet and dry textured proteins from peas and faba beans to the product quality of meat substitutes such as sausages and hamburgers have been carried out. To increase the nutritional value of plant proteins, protein digestibility must be increased, which depends on the texture. We have continued to work with Norwegian-grown vegetables as functional ingredients in vegetarian and meat products, and used various pre-treatment techniques and optimized analysis methods for phytochemicals, antioxidants, fiber and unsaturated fat, and protection against potentially carcinogenic substances and delayed fat digestion, which is linked to an increased feeling of satiety. The effect of the baking aid ascorbic acid, depending on the type of wheat, was studied and provided important insights for wheat growers and the milling industry. Bread with guar galactomannan attenuated postprandial insulin response, predicted by molecular characteristics in in vitro digestion. Alternatives to sucrose were tested in cranberry products to reduce glycemic load. Some semi-refined ingredients from seaweed were suitable as functional ingredients in gluten-free breads, and refined alginate produced bread without a sea taste. Mechanical tenderization and injection of protein hydrolysates into beef muscle improved tenderness and protein digestibility, especially for older adults. Promising results with beef and pork lung in sausages continued, with reduction in cooking loss, increased juiciness and redness when using 10% lung without influencing consumer preferences.",,2024,NOFIMA AS,10031409.13,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P29161,320961,KVAL: Novel biologics tailored for treatment of COVID-19,"The COVID-19 pandemic, caused by SARS-CoV-2, is having a huge impact on health and the economy, and although vaccines have been developed rapidly, there are few therapies available that can be used to treat those who do not respond well to the vaccines. There is therefore an urgent global need for treatment alternatives with a range of complementary approaches, especially adapted to elderly and immunocompromised patients to be developed. In this context, there is an obvious need for biological medicines that have a long-term benefit, and which can be used to slow the spread of the coronavirus, thereby providing effective treatment for those who are already ill or for preventive treatment. Preferably, the designed biological drugs should be tailored so that they can fight the virus where it attacks. Projects have set out to develop a new class of biological drugs that block infection using a unique technology platform, patented by us. The project has led to a drug candidate that binds and blocks SARS-CoV-2's ability to infect cells, and that of all the most relevant virus variants. Throughout the project, a dialogue has been held with a central industrial player about the development, and where the company has shared information and carried out some to test the activity of the candidate. There is now a desire to follow the project further, where the goal is a license agreement, which has not yet been fulfilled. The work will be published shortly, and we will use every opportunity to promote a commercialization run. This is interesting regardless of SARS-CoV-2, as we have experienced that the candidate can also be used in the treatment of other indications.",,2021,OSLO UNIVERSITETSSYKEHUS HF,56569.42,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",,2020 +P29163,320901,"Productive network website for medical doctors, seeking funding for global expansion in response to COVID-19","WoDo is a productive network website for medical doctors. We're currently operational in Norway, under the name ""Norsk Helseportal"" (NHP). Our mission is to assist MDs with any non-patient related task to improve information logistics, knowledge sharing, and efficiency between doctors and healthcare units. The Doctor Networks today occur decentralized on unregulated platforms without full visibility and cooperation, the aim of NHP is to centralize such networks to our secure platform and provide an efficient experience for time consumed Doctors. NHP also gives opportunities for government agencies to reach out to all doctors at the same time. This is important for sharing new regulations and new knowledge critical to the doctor's practice, but also to reaching all doctors during public emergencies and guiding all doctors as a group. During emergencies NHP can even provide the government agencies with important statistics for decision making. We verify that all registered users are in fact licensed MDs, and connect doctors directly to relevant tools, e.g. for job search, courses, discussion forums, shift planners, and calendars.",,,NORSK HELSEPORTAL AS,8485.41,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29165,321313,SARS-CoV-2 infection in HIV-positive patients with or without antiretroviral therapy in sub-Saharan Africa,"The project ""SARS-CoV-2 infection in HIV-positive patients with or without antiretroviral therapy in sub-Saharan Africa"" ​​has published an article describing the project's progress. The article ""COVID-19 and its effects on endothelium in HIV-positive patients in sub-Saharan Africa: Cardiometabolic risk, thrombosis and vascular function ENDOCOVID STUDY"" provides a comprehensive overview of the project's background, goals and approach. During the project period, data has been collected from Nigeria and South Africa. The data sets have different content as South Africa has largely provided a basis for further research on over 200 participants. Various factors meant that follow-up of the patients could not be carried out, partly because skepticism about the health system in South Africa is limited. In Nigeria, fewer patients were included, but more here the possibility of follow-up was easier. This will affect the results. A start-up meeting was held in Mthatha, South Africa in February 2020. Unfortunately, the start-up coincided with the shutdown of many countries, including South Africa, which made fundraising difficult. Regardless, the kick-off meeting in South Africa initiated the project team, which established the basis for the collaboration, defined research questions and planned data collection. During the data collection period, a status meeting was held in Graz, Austria in June 2022. The meeting evaluated the project's progress, identified challenges and adjusted strategies. The partnership was strengthened through the exchange of experience and discussions. After the end of the data collection, a summary and discussion meeting was held in Oslo in October 2023. The results of the study were extensively discussed and assessed during the meeting in Oslo, where the project team together with relevant stakeholders shared insights, challenges and reflections. A final results and article meeting was held in Graz in November 2023. The project reached an important milestone with a dedicated meeting to present and discuss concrete results and the way forward. The article meeting in Graz represented a critical phase in the dissemination of the project's findings to the scientific community. Conclusion The ENDOCOVID STUDY has pursued its overall objective of evaluating SARS-CoV-2 infections in HIV-positive patients, assessing the severity of Covid-19, correlating with comorbidities, analyzing the effect of antiretroviral therapy and assessing the impact of Covid-19 on vascular function and coagulation . The study has collected data from Covid-19 patients in Mthatha, South Africa, and Lagos, Nigeria, over the past two years. The ongoing collection, analysis work and continuous quality assurance have been successful, even with the challenges that the pandemic has brought with it. The partnership has proved robust throughout the project's various phases, and the international collaboration has been crucial to the project's scope and success. The international article and the meetings in Graz, Oslo and Mthatha have served as a platform for sharing knowledge and communicating the importance of the project. The ENDOCOVID STUDY will continue to explore and analyze the data, prepare further publications and contribute to the global understanding of Covid-19's impact on people living with HIV. This report gives a glimpse of ENDOCOVID STUDY's work and challenges and emphasizes the international collaboration.",,2024,HØGSKOLEN I INNLANDET,50573.06,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +P29166,315444,SPRM - Systemic Pandemic Risk Management,"The Corona Commission's third main finding states: ""There is a need to develop a sector-wide system that captures how the risks in the various sectors mutually affect each other."" In other words, the COVID-19 strategy must depend on the assessment and management of systemic risk. The Global Assessment Report on Disaster Risk Reduction 2019 by the United Nations Office for Disaster Risk Reduction states bluntly: ""Realizing the systemic nature of risks, and the opportunities afforded by new approaches and new concepts of risk will be the central challenge of the first half of the twenty-first century."" The SPRM project, in collaboration with Kristiansand Municipality, Sørlandet Hospital, Center for Integrated Crisis Management (CIEM) from the University of Agder and two disaster medicine centers from Sweden and Italy, has created a method and technological solutions for assessing and handling systemic pandemic risk. Systemic risk models are developed in ""participatory modelling"" in workshops with carefully selected experts with relevant expertise in societal sectors affected by the pandemic. The risk model is analyzed and quality assured together with the experts. The analysis methods identify risk scenarios, risk subsystems and find out the most potent risks. Strategies that are most effective and practical are developed against the most potent risks. The SPRM project contributed along the way to the handling of COVID-19 in the Agder county. In the final phase of the project, risk models were created and strategies against future pandemics identified. The SPRM project gained international attention in particular through the report Addressing Complex and Cross-Boundary Challenges in Government: The Value of Strategy Mapping, published by The IBM Center for the Business of Government.",,2023,STEPCHANGE AS,777150.65,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P29167,316092,Development of a novel high-throughput Sars-CoV-2 antibody test,"Norwegian Gentian AS and the University of Tromsø (UiT)/Norwegian Arctic University have collaborated in this project to develop a COVID-19 antibody test. The test detects antibodies against SARS-CoV-2 in human blood, and provides quantitative information on the degree of acquired immunity, even if the person has been non-symptomatic. The test was launched in 2022. Modern technologies for testing antibodies (lateral flow, immunochemical, ELISA, etc.) have disadvantages such as high costs, low throughput (tests per hour) or that they can only be run on closed, proprietary systems. The automated turbidimetric analysis being developed in this project is fast, cost-effective and enables a high throughput (up to 2000 tests/hour. It is intended for use on any platform available on the market. There are over 430,000 different platforms ( clinical chemistry instruments using turbidimetry) at central clinical laboratories worldwide. The test will have close to 100% sensitivity (the ability of a test to identify those who have the disease or the true positive rate), and specificity (the ability to identify those without the disease or the true negative rate). The Gentian SARS-CoV-2 Total Antibody Assay is a valuable tool to: - Provide tools for long-term monitoring of immunity i society - Guiding decisions about herd immunity and vaccination strategy - Documented possibility of protection for the population and for everyone in Norwegian business, including tourism",,2022,GENTIAN AS,905110.67,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Innovation,,,Norway,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29170,316226,CoSAM - Interaction applications in the health service for crises and daily operations,"In the CoSAM project, DNV Imatis has developed new collaboration applications for better workflow, collaboration and task support in the health services in the District of Stovner and the District of Old Oslo. The solutions support employees in working smartly and efficiently on a daily basis as well as in crisis situations and ensure good quality in their work. The COVID-19 crisis presented the municipal health service with an acute interaction challenge that it was not prepared for, and normal routines were not sufficient: There was great uncertainty, great pressure from patients, a great need for information, extensive infection control measures, great logistical needs and it became necessary to change the organization, among other things through establishing fever clinics, reprioritizing regular appointments because many health workers were reassigned and ended up in quarantine. The challenges became particularly clear in handling the corona pandemic, but the municipal health service has the same challenges in daily operations and needs digital tools to support work processes and interaction. The partners in CoSAM have developed, tested and evaluated technology and services through innovation processes that are research-supported and needs-driven. The project has used iterative and user-centred methods. Thorough insight work has been carried out which has established knowledge of the needs of the service and which also documents the previous situation. The insight work documented a great need for a better overview, clearer responsibility and distribution of roles and tools that can make it easier for more employees to follow up a large number of home residents in a better way. The knowledge has been used to develop and adapt work processes and to develop interaction applications for various departments in the health service. The project has piloted and evaluated interaction boards for the home service, assessment team, coping team, the housing unit and several departments in the mental health and substance abuse unit, respectively. The solutions provide better follow-up of users and interaction internally and support work processes for interaction between the teams. The solutions have been developed in close collaboration with managers and employees in the district and through several iterations where the solutions are tested and evaluated along the way. The project has established knowledge about the organization and use of digital interaction solutions that can be reused in municipalities across the country. This is valuable information for other districts and municipalities about how change work and development of support can be done to work smarter and use limited resources as best as possible. Quality improvement and streamlining of services through the acquisition of digital solutions is in line with and well rooted in the municipalities' strategies and national guidelines on digitalisation of health and care services. The project results will also strengthen the healthcare industry and ensure that more and better digital solutions are developed and put into use on a larger scale.",,2022,DNV IMATIS AS,578931.41,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Digital Health,,,Norway,,Clinical characterisation and management | Infection prevention and control | Health Systems Research,"Supportive care, processes of care and management | IPC in health care settings | Health information systems | Health leadership and governance",2020 +P29171,317521,Setting the stage for immersion - project framework for research collaboration,"From ancient times, the recreation of stories has been part of human culture. Through the development of civilization, the practice was refined and resulted in the theater as we know it today. From Aristotle to Shakespeare and Ibsen, the exchange between stage and auditorium has shaped our society and brought stories through the centuries. In the digital age, the theater has many challenges. While other artistic forms, such as music and film, have been able to digitize, resulting in new production tools, global distribution and new artistic expressions, the theater and other forms of performing arts have been left behind. The recent global crises caused by climate change and the COVID-19 pandemic have confirmed that performers, institutions and entrepreneurs who are providers of live performances and dependent on the presence of the public, have an urgent need for alternative operating models with elements of digital content. New models should be explored and developed not only as a response to widespread need and limited mobility, but also with a bold vision to ensure and strengthen the resilience, sustainability and effectiveness of cultural actors, as well as their future opportunity for artistic evolution and audience development, locally and internationally . Virtual reality is the first medium capable of reproducing the scenic expression volumetrically by placing you virtually in the same room as the performer. The rapid development of hardware for virtual presence and motion tracking together with high-speed internet enables advanced two-way communication between digital avatars through the use of game engines and game servers. The Immersive Stage project's goal is to optimize the systems and quantify the methods so that it becomes easy for stage artists to create rich, exciting and powerful experiences for an external audience in VR using digital avatars, scenography, props, costumes, light, sound and visuals effects. The new models of production will help to lower the costs of producing performances and allow global distribution so that more performers can reach a wider audience and make it necessary for cultural actors to recruit new digital skills. This will bring long-awaited innovation to an industry that is characterized by an excess of artistic power, but a deficit in value creation from an underdeveloped market.",,2021,GLITCH STUDIOS AS,28171.57,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",,2020 +P29174,317089,MP: Aminoacridines with dual SARS-CoV2 antiviral and immunostimulating activity,"A group of chemical substances which regulate and which can potentially improve anti-viral immune responses in Covid-19 infection were investigated. In addition, the substances had a direct inhibitory effect on the SARS-Cov2 virus in the test system in the laboratory and based on the characterization of these effects, three drug candidates were formulated for injection and tested for tolerance in animal experiments. A candidate is then selected and the project investigated the effect of this drug candidate with a combined stimulating effect on the immune system and inhibitory effect on the SARS-CoV2 virus in a Covid-19 animal model in hamsters. The studies showed that treatment with the drug candidate leads to a milder clinical course of the disease, somewhat less inflammation in the lungs and somewhat better immune responses, but the effects were not so clear that we have so far been able to convince anyone to invest in further development of a drug candidate. The project has therefore been put on hold and the patent application has not been continued.",,2021,OSLO UNIVERSITETSSYKEHUS HF,56456.28,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P29175,312767,"Fighting pandemics with enhanced risk communication: Messages, compliance and vulnerability during the COVID-19 outbreak","There has been great variation in how different countries' authorities have communicated with their citizens about COVID-19. Nationality thus affects people's vulnerability. At the same time, we know from previous research that other social factors can also be important. The purpose of PAN-FIGHT has been to investigate possible connections between risk communication and individual vulnerability in connection with the outbreak of COVID-19. We have mapped the authorities' communication strategies in Norway, Germany, Sweden, Switzerland and Great Britain in the period from March to December 2020 - i.e. the period from when Europe shut down until mass vaccination started. Furthermore, we have investigated how different population groups in these countries changed their daily routines based on this communication. In addition to nationality, we have looked at the importance of gender and other factors such as age, income, cultural background, family composition and/or place of residence in relation to how the individual has perceived and complied with guidelines for infection control measures. Based on our findings, we have prepared proposals for improved strategies for risk communication that take social, cultural and geographical differences into account. In addition to surveys and surveys, we have maintained close contact with national, local and specialist authorities in the five above-mentioned countries. They have given us information about how they have worked with communication during the pandemic and what kind of new knowledge they need. We have further consulted them in our development of our recommendations to maximize their practical utility. The idea behind the project is that there will probably be more and more serious pandemic viruses after COVID-19. With PAN-FIGHT, we wanted to strengthen national authorities' ability to reach out to several groups in the population, in order to strengthen society's resilience at local as well as national and international level.",,2023,UNIVERSITETET I STAVANGER,560716.06,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience",Communication,2020 +P29179,302336,"Socioeconomic risk groups, vaccination and pandemic influenza","A new influenza pandemic was on the World Health Organization's list of the ten most serious threats to global health in both 2018 and 2019. This is because pandemics cause large numbers of cases of illness, hospitalizations and deaths. In addition, pandemics and serious epidemics can have major economic consequences for both society and the individual, through, for example, the burden on the healthcare system and unemployment associated with the closure of society. The disease and response burdens during COVID-19 have made clear these negative consequences of a pandemic. The core idea of ​​the project ""Socio-economic risk groups, vaccination and pandemic influenza"" (PANRISK) is that influenza can not only be understood as a medical problem, but that the disease's epidemiology and consequences are also governed by social conditions, which in turn can influence who gets sick , who dies and who survives. PANRISK has therefore surveyed the socio-economic background of the risk groups for serious influenza illness, particularly those with chronic illnesses. We have documented that people with a short education and low connection to the labor market (including people with a disability pension) have a higher risk of belonging to a medical risk group for serious illness. We have also investigated how social inequality in education and income can lead to social inequality in flu vaccination. Our findings suggest that free influenza vaccine increases coverage and reduces social inequality in vaccine uptake. In a systematic literature review and meta-analysis, we show that groups with the lowest socioeconomic status had a 1.4 times higher risk of serious illness during the Spanish flu in 1918 and swine flu in 2009 compared to groups with the highest socioeconomic status. How social inequality in morbidity and mortality from influenza can be reduced is neither sufficiently taken into account in current vaccination policy, nor discussed in international and national emergency plans. The PANRISK project has therefore written several articles on how public health authorities can increase vaccination coverage and support for non-pharmaceutical measures among medical risk groups and socially vulnerable groups in society, thereby reducing social inequality in vulnerability during the COVID-19 pandemic, future flu seasons and influenza pandemics. The project is led by the Center for Research on Pandemics & Society (PANSOC) and the Labor Research Institute (AFI) at OsloMet - the metropolitan university. In addition to researchers from AFI, researchers from the Institute of Public Health, Umeå University and the Philadelphia Department of Public Health participate.",,2024,OSLOMET - STORBYUNIVERSITETET,1272246.19,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P29180,300049,Turning recessive epitopes into dominant epitopes: Application to a universal influenza vaccine,"The biggest challenge in vaccine development is to create vaccines against viruses that change frequently, such as the influenza virus, HIV and COVID-19. The problem is that the changes often change the structures that antibodies are directed against. Therefore, when the virus mutates, it will escape destruction mediated by antibodies. The problem would be solved if vaccines could induce antibodies that bind conserved structures that do not change between viruses. Unfortunately, conserved structures are poor at inducing antibodies. Such structures are therefore called immunorecessive (submissive) structures. In order to solve this problem, in this project we will develop a vaccine strategy that makes recessive structures dominant. The basis for the project is as follows: Vaccine molecules that express two copies of a structure induce strong antibody responses, while vaccine molecules that only have one copy induce weak antibody responses. Therefore, if one could make vaccine molecules that express two copies of immunorecessive structures, and only one copy of an immunodominant structure, then the goal might be achieved. Such vaccine molecules can be made with a technology that the project leader and employees have developed. The experiments will be carried out with an influenza protein, hemagglutinin, as antigen. The hope is that the new strategy will induce strong antibody responses against conserved structures on hemagglutinin (HA), and therefore make it difficult for viruses to escape the antibodies. The project will use a newly developed vaccine platform that guides the antigen to the immune cells that start the adaptive immune response, i.e. the antigen presenting cells (APC), in a focused way. The first DNA vaccines have been made and preliminary trials in vitro and in vivo to confirm the quality of the DNA vaccines are underway. Initial trials in mice are promising. These trials are aimed at seasonal influenza. The trials will be extended to bird flu and pandemic flu. The experiments will then be extended to ferrets and monkeys in order to create the right conditions for clinical trials in humans. Hopefully, the project will result in a general vaccine technology that can turn immunorecessive structures into dominant ones. This vaccine technology will be important not only for influenza, but also for other types of diseases such as HIV and COVID-19.",,2024,"UNIVERSITETET I OSLO, DET MEDISINSKE FAKULTET, Institutt for klinisk medisin",1357666.01,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P29181,316277,An AI platform to facilitate the rapid development of T cell based diagnostic tests: applied to SARS-CoV-2,"During 2022, the NOI has continued to work on repurposing the NEC prediction platform, the NEC ""Immune Profiler"" (NIP), to profile the SARS-CoV-2 virus and other pathogens, and identify good immunogenic T-cell targets. In addition, NOI has worked on developing other platforms and statistical tools, which use predictions from NIP and work in tandem with the tool digital twin analysis, which was developed earlier in the project to model the HLA diversity in the human population. This enables the AI ​​platform to identify hotspot combinations (and constitutive epitopes) that are cross-reactive across virus types within the same viral family, and which at the same time have a high degree of coverage in the total human population. This enables the design of blueprints for new diagnostics and vaccines that not only work against specific viruses, but can provide broad protection against new variants or other related virus types. In parallel, OUS has developed a refined ""flow-based-activation-induced"" marker analysis, to further characterize the SARS-CoV-2 test peptides that were identified earlier in the project using the NIP prediction platform. OUS has identified and verified a subset of these peptides that stimulated robust CD4+ and CD8+ T cell ""recall"" responses in PBMCs from both SARS-CoV-2 convalescent individuals and immunized donors. Finally, these peptides were used to screen for vaccine-generated CD8+ T-cell immune responses in cohorts consisting of high-risk immunocompromised patients. The data has been shared with the Norwegian Institute of Public Health and Norwegian health politicians, and has contributed to changing guidelines for vaccination of high-risk immunocompromised patients. The data also clearly show the usefulness of NIP in identifying peptides that can be used in a diagnostic setting.",,2022,NEC ONCOIMMUNITY AS,875128.88,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Innovation,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Diagnostics | Characterisation of vaccine-induced immunity,2020 +P29182,312768,"SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala, Uganda","Uganda's first confirmed COVID-19 patient was identified on March 22, 2020. By the end of 2022, over 170,000 people had been ill with COVID-19. Uganda is estimated to have had 3,600 COVID-19 deaths (https://coronavirus.jhu.edu/map.html), most among people with known risk factors for severe COVID-19. The high population density and the extensive social interaction in the country's cities and villages have created challenges for the country's measures to limit the spread of SARS-CoV-2 infection, the virus that causes COVID-19. It should be emphasized that, on the whole, Uganda handled the pandemic in a good way. To describe the epidemic as it unfolded in Uganda, starting in early 2021, we enrolled women who gave birth in three health clinics in and near the Ugandan capital, Kampala, and followed them until their infants were one year old. We will also try to describe whether some of the mothers and their infants were at higher risk than others of being infected with SARS-CoV-2 and of developing COVID-19. We have a special focus on the vulnerable group of HIV-1 positive women and their babies, therefore we recruited approx. 2/3 of the study participants from this category. By including data from an ongoing prospective study that began before the COVID-19 epidemic arrived in the country, we will be able to form a picture of how the epidemic and the restrictions with e.g. social distancing and limited public transport may have affected the health of these vulnerable mothers and their infants. Our findings will help the authorities to balance the benefits and risks of necessary preventive measures against the spread of SARS-CoV-2 and other pandemic viruses. We also examine how the measures to keep the epidemic in check were understood and experienced by women and their families, and to what extent the measures made it more difficult for them to seek health care. For this work, we have recruited a Ugandan researcher who has applied for admission to a master's degree program at the University of Bergen (UIB) to analyze the extensive qualitative data material she has been instrumental in collecting. If she is accepted at UiB, she will be supported by the HK-Dir-funded project HepEd to complete her 2-year master's degree. The project also includes a randomized controlled trial, where we will investigate whether BCG vaccination can protect less than 14-week-old babies of HIV-positive mothers against SARS-CoV-2 infection and COVID-19. By November 2022, we had enrolled all the planned 1,825 (of whom 1,150 are HIV-1 positive) women and their infants. Our follow-up percentages meet or exceed our own ambitious targets, exceeding 97% at 14 weeks and 90% at 1 year of child age. Our first enrolled mother-baby dyads completed the study in January 2022. The project is carried out as a collaboration between the Makerere University School of Public Health in Kampala and the Center for Intervention Science in Maternal and Child Health (www.cismac.org) at UiB and is financed through the Research Council's GLOBVAC initiative, with co-financing from CISMAC (which is financed by The Research Council and UiB) and the EU's EDCTP2 programme.",,2023,UNIVERSITETET I BERGEN,565694.17,Human Populations,Black,Adults (18 and older) | Infants (1 month to 1 year) | Newborns (birth to 1 month),Urban Population/Setting,Women | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Epidemiological studies | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures",Disease susceptibility | Clinical trial (unspecified trial phase) | Indirect health impacts,2020 +P29183,312757,COVID-19 Public Response and Rapid-Cycle Re-Implementation of Activities,"The project is still ongoing and we expect to end the project in June 2022. -Hospital admissions We have studied acute admissions and death in Helse Sør-Öst during the first lock-down (weeks 12-22). We compared admissions in these weeks with the previous 3 years. We found that acute admissions decreased, mostly for infections (reduced by 49%), acute injuries (reduced by 19%), acute heart attacks (reduced by 18%), cerebrovascular disease (reduced by 10%). There was no reduction in acute stomach disorders. Hospital death after myocardial infarction also decreased (by 34%), and after infections decreased by 19%. This suggests that, although the number of admissions was lower, patients who needed urgent help received it during the lock-down. - Threat, trust and daily life in Norway and Sweden March-April 2020 A questionnaire was answered by 3,500 people. We found that Swedes (37%) had greater trust in the authorities than Norwegians (17%). More Norwegians (66%) than Swedes (18%) think school closures were a good infection prevention measure and that countries that had open schools were irresponsible (Norway 65%, Sweden 23%). More people in Norway believed that the infection prevention measures were a big threat (71% in Norway and 56% in Sweden). In both countries, over 98% followed the infection prevention measures. Many were more relaxed and ate more during the pandemic (69% and 44% in Norway, 50% and 33% in Sweden). People in Sweden trusted their authorities more than in Norway. Trust in the healthcare system and self-reported adherence to infection control advice were high in both countries, despite different handling of the pandemic. - Total mortality We have compared death from Covid-19 and total death in Norway and Sweden in 2020 and compared this with the four previous years. In Norway, we found that the mortality rate was stable from 2015 to 2019 (average 14.9 per 100,000 person-weeks), and was 3% lower in 2020 (average 14.4 per 100,000 person-weeks). In Sweden, the mortality rate was stable from 2015 to 2018 (17.1 per 100,000 person-weeks), lower in 2019 (16.2) and in 2020 the same as 2015-2018 (17.6). Mortality was 3% higher in 2020 than the previous four years, but this is due to lower mortality in 2019. Mortality was only higher for people older than 69 years. The Covid-19 mortality rate was 0.3 per 100,000 person-weeks in Norway and 2.9 in Sweden. Mortality decreased in Norway and increased in Sweden during 2020. The increase in Sweden can partly be explained by the fact that mortality in 2019 was low. - Reopening of gyms: We have completed a study of the reopening of gyms which shows that it is safe to exercise at gyms in Oslo in June 2020. We surprisingly found that more of those in the control group had antibodies against SARS-CoV 2 than in the training group. This indicates that several in the control group have undergone Covid 19. We do not know for sure why, but we observed that there were a number of unorganized groups that trained during the period. This may have led to more infection. It may be that organized training where cleanliness is set in the system and distance rules are observed is a safer form of training than unorganized training. In addition to the aforementioned projects, we conducted semi-structured interviews with various groups in the population, people living in the countryside, people older than 65, people around 50, health personnel, people with chronic diseases, parents of young children and young people in the first round of lock down (16-22 March 2020). We re-interviewed the same people 3-4 weeks later. Data from these interviews has been collected and the analysis work has partially begun. We expect to have completed two scientific publications during 2023 which deal with the fact that there was ""no time for criticism"" and ""fear and uncertainty"".",,2023,"UNIVERSITETET I OSLO, DET MEDISINSKE FAKULTET, Institutt for helse og samfunn",565694.17,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Disabled persons | Individuals with multimorbidity,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Approaches to public health interventions | Indirect health impacts,2020 +P29185,312776,Information Systems for Emergency Diseases Emergency Response to the Covid-19 Pandemic - supporting global and national surveillance,"The main objective of this project was to support low- and middle-income countries (LMICs) with appropriate health information systems, enabling them to respond to rapidly changing information needs during the COVID-19 pandemic and subsequent disease outbreaks. The project centered on DHIS2, the world's largest HMIS platform, used by Ministries of Health in 73 LMICs with 58 national-scale deployments. One of the countries in the consortium, Ghana, adopted the Surveillance Outbreak Response Management and Analysis System (SORMAS). The project consisted of a study of HMIS for COVID-19 tracking in Sri Lanka, Mozambique, Kenya, Ghana and Norway, with the following objectives: (1) assessment of experience with the use of HMIS for COVID-19 surveillance among infection trackers, health managers and national HIS administrators; (2) preparation and use of a data quality evaluation protocol; (3) comparison of HMIS usage experiences across countries; (4) preparation of recommendations to strengthen and improve HMIS for covid-19 surveillance. This research led us to understand the assessment of COVID-19 surveillance platforms in five countries, four of which used the DHIS2 system and one, Ghana, using SORMAS. The project provided important insights into how contact tracers, health managers and national health implementers used digital platforms for disease surveillance, noting features and patterns associated with key variables including simplicity, acceptance of technology and the quality of data collected. Findings on the two platforms have high value for disease surveillance, especially as technologies increasingly participate in the implementation of infection tracing in low-resource environments.",,2022,"UNIVERSITETET I OSLO, DET MATEMATISK-NATURVITENSKAPELIGE FAKULTET, Institutt for informatikk",545781.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Health Systems Research,Health information systems,2020 +P29186,313651,PREDCOV - Blood test to predict the severity of COVID-19,"COVID-19 is an unpredictable disease. As of May 2020, around ~ 4% of those infected had to be admitted to hospital. Of those, ~19% required intensive care and ~18% died. Vaccines, better treatment and the omicron variant have contributed to the fact that the prognosis for COVID-19 has improved significantly, but it is still challenging to know in advance who will get a serious illness. In this project, we have discovered an epigenetic pattern that can distinguish patients with severe COVID-19 disease from those with a mild course, with a high degree of accuracy. We have investigated that the pattern correlates well with the severity of the disease, in more than a thousand patients distributed across the USA, the EU and Norway. We have further developed our discovery in the form of a prototype where we have shown that the pattern can easily be measured on laboratory equipment found in normal hospital laboratories. We are now working with commercial partners to set up a full-scale test in a clinical laboratory. The project has been a collaboration between the newly started diagnostics company Age Labs, the Institute of Public Health, Oslo University Hospital and Bærum Hospital.",,2022,AGE LABS AS,679172.42,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29187,312721,"COVID-19 in Norway: A real-time analytical pipeline for preparedness, planning and response during the COVID-19 pandemic in Norway","The coronavirus pandemic is a threat to people's health worldwide. It has already caused great damage to many societies. Politicians need high-quality data on the spread of this infection to be able to choose good measures. We use both mathematical models and collect data on symptoms from the population to provide a detailed picture of the epidemic in Norway. An important way to limit the spread is to reduce person-to-person contact. We collect data about people's movements in society with the use of mobile phones. This, together with data on symptoms of disease in the general population, enables us to estimate the contagiousness of the corona virus and provide good forecasts for the spread and the number of hospitalizations in the short term. The models provide politicians with important information by showing how various measures, such as prioritizing vaccines and isolation, can reduce the spread of infection. Long-term scenarios are run to provide insight into the possible development of the epidemic, which is used in risk assessments. The methods we use are at the forefront of research when it comes to statistical science, and will be important for strengthening preparedness against other infectious diseases in the years to come. We collect data in existing population surveys, such as the Norwegian Mother, Father and Child Survey (MoBa) and the Norwegian Influenza Study (NorFlu), and we link data to register information on COVID-19 incidence, in order to understand why some people have higher risk of infection and serious illness than other people. These examinations include important information based on previous genetic and immunological analyses. Such information, together with data on education, occupation and previous illness, provides an understanding of how SARS-CoV-2 will affect the population's health. We also analyze the entire Norwegian population based on the central personal register. To this register we link information from the patient register, the primary health register, the reporting system for infectious diseases and the cause of death register in order to be able to describe and understand the consequences of the epidemic in Norway.",,2022,"FOLKEHELSEINSTITUTTET, Område for smittevern, miljø og helse",565694.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease transmission dynamics | Disease susceptibility | Indirect health impacts,2020 +P29189,312773,COvid19 Network Technology based Responsive Action,"The project ""COVID-19 Network Technology-based Responsive Action"" (CONTRA), June 2020 - March 2022, focused on supporting public health authorities with the delivery of a COVID-19 vaccine in a country, particularly in low- and middle-income countries. The goal was to develop an intuitive web-based decision support system (DSS) to help allocate COVID-19 vaccines to different locations and groups in a country within a short time frame. To achieve its objectives, the project followed five steps: (i) stakeholder analysis and definition of the COVID-19 supply chain; (ii) identify key performance indicators (KPIs) to assess the system, (iii) mathematical modelling, (iv) analyze different realistic scenarios using the model, and (v) present the set of best-in-class allocation options to public health authorities. The result of the project can be summarized as follows. Firstly, we studied the problem in close collaboration with health authorities from Norway and Belgium. It was found that the distribution of COVID-19 vaccine in a country could be examined at central and local allocation levels. While the problem at the central level can be generalized to many contexts (high-, middle-, and low-income countries), the problem at the local level was found to be significantly context-dependent. The central problem concerns the distribution of vaccines from central warehouses to the regional storage facilities in a country after vaccines have been received (and repackaged) at the main entry points (e.g. airports). The local problem involves receiving the vaccines at regional facilities and administering them in vaccine administration points to target groups. The CONTRA project had a focus on low- and middle-income countries, but researchers on the project could only get in touch with key decision-makers mainly in high- and upper-middle-income counties for a short time. Therefore, we targeted the central allocation problem. Second, we found that public health authorities tracked the achievement of five main goals in vaccine allocation in that problem at the central level. Despite limited vaccine supply, they focused on vaccinating as quickly as possible, vaccinating as many as possible, vaccinating in line with priority and other guidelines set by the responsible coordinating body (e.g. the Institute of Public Health), equitable access and public trust in vaccination. However, the public health authorities experienced several challenges in achieving these goals: extracting doses from vials, handling changed dose intervals, deciding whether to discard a vaccine or use it, establishing computer systems for calling in patients and distributing vaccines, and not at least, to balance the need for operational staff with the need for training. Our findings support identifying ways central government can promote a harmonious, coordinated national pandemic response, while allowing for distributed improvisation. Third, CONTRA developed a new mathematical model to support public health authorities in achieving the above objectives. The model focuses on equitable access to vaccines and it can produce allocation strategies within seconds. The model seeks a ""fair level of coverage"", which is calculated based on the size and importance of several regions and population target groups. The results of testing the model on different COVID-19 datasets from Turkey indicated that the factors used for prioritizing regions can result in significantly different allocation decisions. We also found that the limited capacity of facilities at municipal and regional level can significantly hamper the fairness of the entire vaccination system. It is therefore understood that a system must be developed that can incorporate several potential scenarios before or after the presentation of solution alternatives to public health authorities. Fourth, the CONTRA team developed a decision support system (DSS) that incorporated our mathematical model into an online user-friendly dashboard to support vaccine allocation. Several validation meetings were held with representatives of public health authorities from different countries where the system was tested with different scenarios and datasets. The validation result revealed that deciding on vaccine allocation is indeed a complicated task, but the authorities often do not have enough time, resources and knowledge to incorporate sophisticated decision support tools. As a result, allocation decisions have been criticised. Several tests of the developed dashboard at the CONTRA project showed that the need for intelligent systems to support the vaccine allocation problem in real operations was a realistic assumption. Based on the findings above, we have identified several future research directions that can be found in the project's reports no. 1-4.",,2022,"UNIVERSITETET I AGDER, FAKULTET FOR TEKNOLOGI OG REALFAG, Institutt for IKT",453007.89,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Vaccine logistics and supply chains and distribution strategies | Vaccine trial design and infrastructure | Policy research and interventions,2020 +P29190,317107,Ventura,"Currently, European health care systems face many challenges. In addition to financial and transformational problems caused by increasing patient numbers and rising of their expectations, the major problem is connected with the health workforce: • The High-Level Commission on Health Employment and Economic projected a global shortage of 18 million health workers by 2030. For Europe, the gap in the supply of and demand for health workers in 2030 will be at least 1.4 million employees, including 300k physicians , 700k nurses and 400k other health workers [ ]. • Health workers are exposed to a complex variety of health and safety hazards every day, including sharp injuries, harmful chemicals and hazardous drugs, back injuries due to heavy lifting and, first of all, highly infectious diseases such as tuberculosis, hepatitis B and C , HIV/AIDS as well as emerging infectious diseases like SARS, H5/N1 influenza, COVID-19. Some statistics on occupational infectious diseases in health workers are needed. • 78% of physicians and 38% of nurses experience burnout and reduction of work efficacy due to the health care staff shortage, overworking, long shifts, excessive and prolonged stress [ ]. All these results in poor and wrong decisions, depersonalization, lack of empathy and, therefore, increased chances for patients to stay in the hospital longer and/or return with complications. The pressure rises exponentially in the case of natural or technogenic disasters and, especially, epidemics. On-going COVID-19 pandemic demonstrates global unpreparedness of national health care systems and particular vulnerability of health workers. Data on cases/deaths among health workers... EU/national statistics. These challenges and pressures can be tackled by the introduction of Artificial Intelligence (AI) and Robotics solutions to the every-day operations of the health care facilities to support human workers.",,,HALODI ROBOTICS AS,6788.33,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Health Personnel,Unspecified,,Unspecified,,,,,,,,,Unspecified,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Health Systems Research,,2020 +P29192,312770,The Smartphone Pandemic: Mobile technologies and data in the COVID-19 response (SMARTCOVID),"The corona pandemic is the first pandemic in the smartphone era. New technologies such as infection-tracing apps and location data from mobile phones have been used to model, observe and control the pandemic. The use of such technology has received a lot of attention and led to major discussions around digital surveillance and privacy, while at the same time it has given hope that the technology can help us end the pandemic. The ""Smartphone Pandemic"" project has researched the social, political and ethical consequences of the use of smartphone technology to combat the corona pandemic, focusing on how it changes structures, power and norms in public health. The project has aimed to strengthen the knowledge base on digitization in public health during a pandemic and to ensure ethical and fair use of new technology. Based on case studies in various countries (Sierra Leone, Myanmar, Japan, Taiwan, Great Britain and Norway), we have analyzed how health authorities have adopted such technology, and mapped how various institutions attempt to manage the use of smartphone technologies and digital health data in times of crisis . The project has also investigated how the experiences with the use of mobile data in Sierra Leone and Myanmar during previous disease outbreaks were used in Norway during the corona pandemic. Increased power for the technology companies An important research result from the project is that the pandemic has led to new forms of collaboration between large technology companies and public health authorities that challenge established norms in public health and digital sovereignty. Such collaborations have focused on digital infection tracking, epidemiological modelling, and communication through social media and chatbots to deal with an ""infodemic"" of more or less reliable information about the new coronavirus. We have studied how the digital response to the corona pandemic shows that technology companies have gained increasing power in public health. This involves the promotion of technological solutions that may seem attractive to politicians, but which lack documentation on whether they are effective and what kind of social and political consequences they may have. Infection tracking apps did not have the desired effect The research results show how the use of digital infection tracking and other digital solutions as political tools depends on contextual factors, such as how authorities in different countries relate to public health services and whether they have an optimistic view of technology. An important finding across the various case studies is that apps designed to locate and trace infections have a limited effect on the spread of infection and have not solved management challenges related to health and pandemics. Digital solutions have also failed to help those most at risk of falling ill from the coronavirus. Both such interventions and digital solutions aimed at opening up society after the corona pandemic (e.g. digital vaccine certificates) may risk shifting the focus away from traditional public health measures and undermining attempts to equalize social inequalities in health. Ethical considerations must be included in pandemic management The project has highlighted how technological solutions were implemented during the pandemic despite weak or missing documentation and regulation. The technologies were often based on previous experimentation in low-income countries that rarely benefited the citizens of those countries. For example, the models Telenor and the Institute of Public Health used to track the spread of infection in Norway were developed in Myanmar and Bangladesh before the pandemic. The myriad ethical issues related to smartphone technology used during the pandemic-including privacy, curtailment of civil rights, and the setting of health policy by a technological elite-highlight the need to involve ethicists in pandemic management and preparedness. Challenging uncritical techno-optimism The research results are valuable information for governments and provide insight into which smartphone technology may be successful and which are most likely to fail. The results challenge uncritical techno-optimism in pandemic management and underline the importance of sustained investments in public health and pandemic preparedness that equalize social inequalities and prioritize those at greatest risk of infection and disease during pandemics. The project has strengthened interdisciplinary and international collaboration between researchers from anthropology, political science and international relations, and political philosophy, and has contributed to a growing field of critical social science research on digital technologies and data within pandemic management and preparedness. The project has worked actively to communicate the research results and has published several academic articles and commentaries, and given presentations at conferences. A wider audience has also been reached by writing comments and chronicles in both Norwegian and international media, participating in webinars and podcasts, and giving interviews.",,2022,"UNIVERSITETET I OSLO, Senter for utvikling og miljø (SUM)",393949.42,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Digital Health,,,Norway,,"Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Research to inform ethical issues related to Public Health Measures | Communication | Social impacts | Other secondary impacts,2020 +P29193,312751,COVIDOSE: Determining infectious dose for SARS-CoV-2 and assessing contact/proximity risk,"The main goal of the COVIDOSE project is to estimate the infectious dose of the coronavirus SARS-COV2 that causes COVID-19, and use this to develop risk models for getting sick from coming into contact with the virus in different ways. The infectious dose for a pathogen (virus, bacteria, fungus, etc.) is the number of individual bacteria / viruses that must enter your body to make you sick. This dose varies by many orders of magnitude between different pathogens, and may also vary with the route by which it entered the body. However, having an infectious dose is very useful for designing practical security measures, as it lets you know how effective, time consuming and expensive they need to be - and how sensitive the controls - need to be. It also allows you to calculate the risk accumulated by coming into contact with several small doses of the pathogen and so on. To estimate the infectious dose for SARS-CoV-2 in humans, we will isolate and sequence thousands of individual virus particles from individual patients. We find variance between the genomes of the individual virus particles in the form of mutations. However, these mutations occur over time at a fairly regular rate, so large genomic datasets will allow us to calculate the rate at which these mutations occur. This is called a molecular clock. By combining the genetic variability between patients and within individual patients with this molecular clock, we can estimate how large a population of viruses first started the infection in each patient. We collaborate with other Research Council of Norway projects at FHI and FFI to study contagion and development between connected cases of covid-19. This will allow us to create models and estimates of becoming infected that will inform epidemiological studies.",,2023,"UNIVERSITETET I OSLO, DET MATEMATISK-NATURVITENSKAPELIGE FAKULTET, Institutt for biovitenskap",484686.77,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease pathogenesis",2020 +P29194,317056,MP: NTNU COVID-19 test,"After several weeks of intensive testing for the coronavirus, St. Olav's hospital was about to run out of test equipment. In order to prevent a lack of test material, as well as dependence on commercial players, an interdisciplinary group of researchers from NTNU joined forces to develop a separate test method for diagnostics of SARS-CoV-2. The result of the work is a new and improved method for COVID-19 RNA extraction, and the method is based on interdisciplinary expertise in nucleic acids and magnetic nanoparticles at NTNU. The result is an in-house developed and optimized chemical mixture to open up the virus as well as the production of magnetic nanoparticles to be able to extract the virus' genetic material. Preliminary results indicate that the NTNU-developed test is at least as sensitive compared to the best methods on the market. There is a large global demand for test reagents and the NTNU team has received a lot of international attention. One possible way to make the technology available is through collaboration with existing industry players for international distribution. This milestone application aims to clarify which industry requirements must be met in order to be able to make the technology available internationally and in this way be able to contribute to easing the burden of the pandemic.",,2021,NTNU TECHNOLOGY TRANSFER AS,45368.67,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,Innovation,,,Norway,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29195,302597,India's Footprint in Africa: South-South Cooperation and the Politics of Gifts and Reciprocity,"There is great interest and rivalry among the major world powers for influence in Africa. Some argue that a ""new battle for Africa"" ​​is taking place, with major Western powers and newer global players such as India and China all vying for the continent's attention. An important channel for Indian engagement has been through South-South cooperation (SSC), where India promotes the so-called Triple A technology (Affordable, Accessible, Adaptable) as an alternative to Western models. In particular, health and education through ICT has enabled India to differentiate its SSC activities from China's. Our focus in this project is India's competitive advantage in ICT, education and health skills (including Covid-19 vaccines). A key objective is to better understand how India's SSC engagement affects socio-economic components in three African countries; Senegal, Malawi and Mozambique, as well as perceptions of and the significance of India's increased influence. Findings: In recent years, India has stepped up its global ambitions and its foreign policy engagement with African countries. India is now the third largest export destination and the fifth largest investor on the continent. At the same time as India tries to challenge China's dominant presence in Africa, the country has signed a number of bilateral agreements. India has also strengthened its diplomatic presence and is actively promoting trade, infrastructure and private sector investment. It appears in our research with the University of Mumbai that India has good expertise in sharing digital skills related to access to universal health services. On the African continent, New Delhi has renewed its infrastructure for telemedicine and online video consultation. The effect is a cost-effective and safe alternative for the treatment of infectious diseases. During the pandemic, India's expertise in affordable holistic services has gained greater importance. New Delhi is already reaping the benefits of an ambitious diplomatic initiative aimed at supplying Indian-made vaccines to developing countries. As one of the world's largest drug producers, India produces 60 percent of the global share of vaccines. Several African countries have bought these medicines, or received them as gifts. India has strengthened its diplomatic ties and its global recognition as a result of its capacity and willingness to share COVID-19 vaccines. However, the second wave of infection in May 2021 led to a decision to stop vaccine exports. This created a bump in the road for India's reputation in Africa, but we expect India's reputation to be restored as soon as vaccine supply resumes. Since 2018, the India-Africa partnership has been based on a set of principles that have emphasized ""local priorities"". A joint effort to change global institutions, overcome climate change and fight global terrorism are overarching requirements. The principles also highlight capacity building for agriculture, education, digital technology and cooperation around peacekeeping and maritime issues. How, and to what extent, can Africa benefit from India's growing interest in the African continent? We identify three sets of health-related benefits and opportunities that could shape the future of the India-Africa relationship. The first deals with India's reputation as ""the world's pharmacy"". India has actively contributed to meeting the global demand for vaccines, over-the-counter medicines and affordable generic medicines. As production costs are low, Indian products are cheap all over the world. Africa receives nearly 20% of India's pharmaceutical exports, which equates to $17 billion. Southern and western regions of Africa represent the largest importers of Indian medicines. This includes antiretroviral (ARV) drugs, which are far less expensive than the drugs produced by Western companies. The second concerns cooperation and capacity building in the health sector. Indian healthcare professionals collaborate with African partners, and some have opened or are planning to open specialist hospitals in several parts of Africa. India has also grown to become an attractive destination for 'medical tourism' by offering good healthcare services at competitive costs. The third concerns India's active ""medical diplomacy"". Africa relies on affordable medicines, including a COVID-19 vaccine; a need that will probably only increase in the future. At the same time, India can learn from Africa's success in preventing the spread of the Ebola virus. More experiences with disease control in African countries will thus also be able to contribute to improving India's health sector. Together with our partners at the University of Malawi, we have started to study the Pan-African E-Network (PAEN) project at Chancellor College in Malawi, more specifically the ""tele-education"" component. We have conducted several interviews with relevant actors, including the Indian diaspora. However, what we have not found sufficient information about is the telemedicine component of PAEN.",,2024,"UNIVERSITETET I OSLO, Senter for utvikling og miljø (SUM)",616719.79,Human Populations,Asian,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2020 +P29198,312780,"Norwegian SARS-CoV-2 study - Virological, clinical and immunological characterization of inpatients during the COVID-19 outbreak","Diseases caused by infections are the most frequent cause of death worldwide. New infectious agents, such as SARS-CoV-2, must undergo a lot of research to gain knowledge of the virus's biology and ability to induce disease (pathogenesis) in the host. In order to gain a good mechanistic understanding of the disease process, it is necessary to identify risk factors for serious disease and find which therapy is effective, as well as examine the virus's ability to multiply and its dynamics in addition to the host's response. By studying immune responses over time in the host and which factors affect this, it can provide knowledge about individuals' susceptibility. At Oslo University Hospital, we started the ""Norwegian SARS-CoV-2 study"", which is an observational study on the newly discovered SARS-CoV-2, the coronavirus that causes the COVID-19 infection. The study was quickly approved by the Regional Ethics Committee in February 2020, and afterwards inclusion was underway with the first confirmed COVID-19 cases that required hospital treatment at the start of the pandemic. The study is expected to provide a lot of knowledge about the course of COVID-19 infection, as well as generate a lot of data about the virus and its mode of transmission.",,2023,"UNIVERSITETET I OSLO, DET MEDISINSKE FAKULTET, Institutt for klinisk medisin",563883.95,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis",2020 +P29200,312740,"COVID-19 Seasonality: The effect of environmental variation on the spatio-temporal dynamics at national, regional and global scales","COVID-19 Seasonality was a Norwegian-based project with close collaboration with leading research and preparedness organizations in China, Iran, the UK, the USA and the African Union to develop basic information and inform the response to the ongoing covid-19 pandemic. The objectives were organized into three main measures: (I) Map - to find out how weather and seasonal factors affect the growth pattern of the covid-19 epidemic; (II) Predict - to use data on weather and seasonal factors such as covid-19 to assess how the epidemic will change in the future in Norway and other countries; and (III) Prepare - to evaluate the risk of future pandemics, similar to covid-19, in Norway and other countries from new and emerging infectious diseases (EIDs). Articles relevant to all three objectives have been published as a result of the scientific work and collaboration in the COVID-19 Seasonality. COVID-19 Seasonality has produced quantitative models to predict the seasonal conditions in Norway and other countries that promote and prevent transmission of SARS-CoV-2, which has improved the predictions of epidemic trends. COVID-19 Seasonality then applied fundamental research approaches and the insights gained to improve understanding of the spatial and temporal dynamics of COVID-19, and the impact of existing or potential interventions during the pandemic. Overall, this work contributed to improving preparedness against future diseases both in Norway and globally. The project created a strong dialogue with both national and international partners and has contributed to developing new research areas that are still being explored.",,2024,"UNIVERSITETET I OSLO, DET MATEMATISK-NATURVITENSKAPELIGE FAKULTET, Institutt for biovitenskap",456854.61,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +P29201,312730,Monitoring the population seroprevalence of SARS-CoV-2 infection in Norway to model and predict the current and future epidemics (Map-SARS),"Until 23 June 2022, 539.1 million people had been diagnosed with Covid-19. This number consists only of those who have actually tested themselves and had live virus detected in their bodies and is therefore lower than the actual number of those who have had the disease since March 2020. An article from the Lancet from 2022 estimates that 44% (or 3, 4 billion) have been infected. The gap in registered infected and the number of likely infected is therefore large and this was the background for carrying out the study, many in Norway believed that this gap was also large in 2020/2021. The number of those who have been diagnosed as ill can be used for a lot, but in order to understand the disease and its spread in Norway even better, it would have been nice to know how many people have actually had the virus in their bodies since the pandemic broke out. To find this out, you can test, via a small blood sample, the presence of so-called antibodies. If they are present, you have had the virus in your body at one point or another. If, for example, the total number of confirmed infected people in Norway was 1% and a representative sample of participants in a study shows that 3% have antibodies, we understand that the official number of infected people is greatly underestimated. In this project, we collected blood samples from 27,700 people living in Norway at the end of 2020 and the beginning of 2021, all over the age of 16. The samples showed that 0.9% had antibodies and had the virus in their bodies. The official number of infected people at the same time was 0.8%. In other words, there were very few cases in Norway that were not registered. It shows again that the testing, isolation, infection tracing and quarantine arrangements (TISK) we had in Norway were very effective. It is a very important lesson to take with you for the next time something like this happens.",,2023,"UNIVERSITETET I TROMSØ - NORGES ARKTISKE UNIVERSITET, DET HELSEVITENSKAPELIGE FAKULTET, Institutt for samfunnsmedisin",565694.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Epidemiological studies,Disease surveillance & mapping,2020 +P29202,311399,Molecular interactions important for Axl activation,"AXL is a receptor tyrosine kinase that is highly expressed in several cancers, and activation of AXL is associated with cell survival, proliferation, migration and immunological response. Because AXL is involved in many cellular processes across different malignant tissue types, there is a critical need to understand and modulate Axl signaling in the tumor microenvironment. The aim of this project is to improve the understanding of the molecular mechanism of the interaction between AXL and GAS6, PtdSer, and the therapeutic antibody tilvestamab by using structural biology as a research method. The methods used are cryo-electron microscopy and X-ray crystallography. After the global Covid pandemic had started, AXL was identified as a possible binding partner of the spike protein of COVID-19. A collaboration with Professor Wendy Maury at the Universitiy of Iowa confirmed that AXL mediates an increase in COVID-19 infection. This project also showed that the mechanism is not through a direct interaction with the spike protein, but rather an interaction with a lipid in the viral membrane. These results are now part of a publication in the journal PLoS Pathogens.",,2024,BERGENBIO ASA,266328.82,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",,2020 +P29203,317044,Digital twin for COVID-19 in Nursing home,"The COVID-19 pandemic is impacting the global population in drastic ways. In the EU/EEA and the UK, older people are facing the most serious threats and challenges of COVID-19. Nursing homes, a type of Long-Term Care Facilities (LTCF), are high-risk setting for COVID-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel. A recent systematic and meta-analysis of 172 studies across 16 countries and six continents shows that the risk of transmission of viruses can be reduced by setting a physical distancing of 1 m or more and/or wearing a face mask2. Conceivably, these two methods could minimize the virus spread that would have occurred through direct/indirect droplet contacts and airborne aerosol particles3. However, these two methods are challenged particularly for the elderly with hearing difficulty and breathlessness in LTCF. Thus, it is urgent to search for a more effective alternative measures to prevent the spread of SARS-CoV-2 in LTCF. The hypothesis of DiCoV proposal is that efficient ventilation of LTCF could substantially reduce the airborne transmission of SARS-CoV-2. This is based on recent studies showing that the transmission is mainly mediated via aerosols than via fomites, and that typically poorly ventilated and populated spaces, like nursing homes and public transport, are core sites of the viral transmission",,,HAFENSTROM AS,6788.33,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Epidemiological studies | Clinical characterisation and management | Infection prevention and control,"Disease transmission dynamics | Supportive care, processes of care and management | Clinical trials for disease management | IPC in health care settings",2020 +P29206,312693,Defining the immune cells in COVID-19 that correlate with disease severity,"The project uses advanced multi-parameter analyzes to follow immunity and disease in COVID-19 patients and in healthy or post-vaccination patients. During 2021, we have published articles describing serious side effects of the AstraZeneca vaccine published in NEJM and EHJ. The project has made it possible for us to initiate a number of activities and obtain additional funds, including the first project from the international vaccine alliance CEPI for a Norwegian group, an observational study, an interventional vaccine study (2021-003618-37) and further follow-up of patients with severe venous thrombosis after covid-19 vaccination in Norway. We will publish a number of articles defining cellular responses to corona vaccines in immunocompromised individuals, we are now monitoring immune responses from the third and fourth revaccination of high-risk groups. We compare immune responses against the wild-type, alpha and delta variants of the coronavirus. We also analyze cellular immune responses of family members participating in the household study where FHI researchers recruit participants from families where one or more have developed covid-19 disease. We measure the levels of protective cellular immune responses in vaccinated healthcare workers and immunocompromised patients. The results have been reported to the Institute of Public Health, the Directorate of Health and have helped the government to make decisions. The project continues within the framework of the CEPI project and other funding.",,2023,OSLO UNIVERSITETSSYKEHUS HF,181927.25,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +P29207,312717,CovidNor - Experiences of patients and primary health care professionals during the COVID-19 epidemic in Norway,"Most patients with COVID19 have a milder disease course and are treated outside hospital. In the CovidNor project, we have examined the symptoms, complaints and concerns of patients treated in the primary healthcare service, and we have explored how GPs and municipal doctors handle the pandemic. The project has consisted of three work packages: 1. An online survey, where we have collected information about symptoms, follow-up and concerns of people in isolation or quarantine. The study took place from March/April 2020 until July 2021. Results are expected soon in scientific journals, and some will be presented in relevant forums. We will later link this information to data from various health registers to identify possible factors that are associated with the development of a more serious disease course as well as possible complications and long-term effects of COVID19. 2. Through the PraksisNett research network, GPs registered information on how patients with respiratory infections were in contact with the doctor, examined, treated and followed up during the pandemic. Preliminary results from this have been presented orally in research forums. A scientific article is currently being prepared. 3. We have conducted in-depth interviews with GPs, emergency department chief doctors and municipal chief doctors in Norway and infection control personnel in Sweden about handling the pandemic. We have focused on the collaboration between GPs and the municipality, management, communication and division of tasks, and adaptation to a situation characterized by rapid changes. A scientific article is expected to be published in 2022, and remaining material is being analyzed for future publications.",,2022,"UNIVERSITETET I OSLO, DET MEDISINSKE FAKULTET, Institutt for helse og samfunn",565694.17,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29208,312759,"Emotional Contagion (EmotiCon): Predicting and preventing the spread of misinformation, stigma, and anxiety during a pandemic","Misinformation, stigma and anxiety have spread in the population in the wake of the COVID-19 pandemic. In the ""Emotional Contagion"" (EmotiCon) project, we were to explain how and why this happened in Norway. We did this by developing a social simulation of Norway; a multiagent artificial intelligence model. This was designed so that it can help us understand how social stigma and anxiety spread in the population in parallel with the virus infection. This type of knowledge can therefore also be used to predict and help reduce misinformation, stigma and anxiety when societies such as Norway prepare for the next pandemic, or pandemic wave. The EmotiCon project has been carried out by CMSS (Centre for Modeling of Social Systems) in NORCE. To develop the EmotiCon model, we have collected large amounts of data, from social media and from two national surveys taken during different periods during the pandemic. In these surveys, representative panels of the population are interviewed along several dimensions linked to the theme of the project. The EmotiCon model was developed in collaboration with a team of international partners and national subject experts. The EmotiCon project has had a reference group which has consisted of subject experts from ten city municipalities in Norway. The computer model EmotiCon contains simulated agents that have cognitive architectures and weighted social network ties that influence their beliefs and behaviors based on a variety of social psychological theories. These agents have then been empirically calibrated and validated in relation to data on the Norwegian population collected through surveys and analysis of social media. Therefore, the knowledge developed in the EmotiCon project can provide stakeholders with an empirically validated 'artificial community', a simulation platform, in which different types of scenarios and intervention strategies designed to mitigate the spread of anxiety, stigma and misinformation during future pandemics can be tested. The EmotiCon Team has so far had three academic articles accepted for publication. One of the articles deals with the model itself, one with the participation process and one deals with questions related to why some choose not to take or are hesitant in relation to vaccination. The EmotiCon team has three more scientific papers from the project in preparation. The EmotiCon project has so far been presented at four scientific conferences. In the project, a policy note has been created for the reference group and a further policy note will be presented in connection with the final meeting of the reference group in spring 2022.",,2022,"NORCE NORWEGIAN RESEARCH CENTRE AS, NORCE NORWEGIAN RESEARCH CENTRE AS AVD KRISTIANSAND UNIVERSITETSVEIEN",353106.3,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience",Communication,2020 +P29209,312862,R&D agenda for recovery and growth in Norwegian tourism 2020-2024,"The purpose is to increase business-oriented R&D activity for tourism in order to underpin the need for change in the industry after the Covid-19 pandemic. Development of a joint R&D agenda for the tourism industry should result in the design of several applications for the Research Council's announced calls for proposals (e.g. Competence and collaboration project, Innovation project in business), upcoming calls for proposals and EU project(s). A common R&D agenda will also be important to identify knowledge needs that are not covered well enough by existing arrangements within the instrument apparatus. The project will result in increased business-oriented research and development in tourism in order to rebuild the industry after the Covid-19 pandemic. The project has identified research needs to rebuild the industry after the COVID-19 pandemic. The application ?Transformation and Sustainable Growth of the Norwegian Travel Industry? (project 322732) was prepared as part of the mobilization project with a broad corporate partnership: Thon Hotels, Nordic Choice Hotels, Radisson, Norlandia, De Historiske, Scandic, SAS, Hurtigruten, Color Line, NSB, Fjord Tours, Fjord Norge, Visit Oslo, NordNorsk Reiseliv , Alpinalleggenes Landsforening, Komon-Stageway, and Innovation Norway. These cover large parts of Norwegian tourism and will share data and be involved in the various work packages. The project has mobilized a strong research team with experienced researchers from the University of Southeast Norway, the University of Tromsø, New York University, Deutsche Institut für Tourismusforschung and Victoria University New Zealand. The project submitted an outline for ""Norwegian Travel Industry Monitor: Digital lab for big data analysis of economic development of businesses and destinations"" (project 316606). This project was decided to be postponed until 2023 due to the corona burden on the industry as a result of the pandemic's escalation in autumn 2020 and the authorities' closure of the tourism industry.",,2021,NORSK REISELIV/NORWEGIAN TOURISM PARTNERS,56456.28,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",,2020 +P29210,312688,Detection and temporal monitoring of SARS-CoV-2 in Norwegian hospitals and other high transmission risk environments (NorCoV2),"With its rapid spread and significant mortality, COVID-19 poses an enormous challenge to global public health and societal security. A central component in the work to limit the outbreak is to limit the rate of spread within populations. This requires a deep understanding of exposure risk in different environments and different situations. Risks to healthcare workers must also be addressed, given the importance of a well-functioning healthcare system in a pandemic. The NorCov2 project has collected environmental samples from hospitals, metro stations and an airport; three environments that are very important for the spread of infection. Both air and surface samples have been collected regularly (every/every two weeks depending on infection pressure) at airports and subway stations from the start of the outbreak in Norway until the end of 2020. A total of 434 surface and 135 air samples have been collected from public room. SARS-CoV-2 virus was detected in surface samples collected at subway stations and inside subway cars. Testing of SARS-CoV-2 in the air around hospitalized patients and infected persons with less severe symptoms is carried out in collaboration with Oslo University Hospital. An experiment evaluating the effect of treatment with a nebulizer on the amount of virus in air showed that the amount of virus was higher during treatment compared to control, and that this increase coincided with an increase in smaller particle sizes which can be taken as an indication of the transport of virus in aerosol particles. Only a small number of samples were positive, these taken around patients with very strong symptoms. Furthermore, viruses were detected in the air around COVID-19 positive people who were not hospitalized and had mild symptoms. All samples that were PCR positive were attempted to be cultured; none of these were positive. The results from the project showed no environmental contamination at Oslo Airport, but some positive samples were found at subway stations and in subway cars. As these results are based on a limited data set (434 surface and 135 air samples), they cannot be taken as proof of the absence of infection risk; in addition, the methodology used in the project will not be able to detect direct infection between people, which is considered the most important route of infection. Furthermore, the results indicate that there is a potentially higher risk for healthcare workers when patients are given nebulizer treatment, and that the risk is also higher when the patient has more severe symptoms. More samples taken of air around people with mild symptoms, who are not hospitalized? and which can thus cause the spread of the virus? were also positive. NorCoV2 is led by the Defense Research Institute, in collaboration with the Defense Microbiology Laboratory, Oslo University Hospital, Sporveien AS, and Avinor AS. The NorCoV2 project has also contributed data to an international environmental monitoring project for SARS-CoV-2, under the coordination of the MetaSUB consortium (metasub.org).",,2021,FORSVARETS FORSKNINGSINSTITUTT,218923.64,Environment,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Environmental stability of pathogen | Disease transmission dynamics,2020 +P29211,312712,Survival rates and long-term outcomes for patients with COVID-19 admitted to Norwegian ICUs,"The study Survival and late symptoms for patients admitted to intensive care with Covid-19 in Norway is a collaborative project between Oslo University Hospital and the Norwegian Intensive Care and Pandemic Register (Helse Vest), and has a twofold purpose. The first part of the study consisted of describing (e.g. age, gender, risk factors) the Norwegian Covid-19 population who received treatment in intensive care, and examining survival. The second part of the study was to investigate the incidence of late symptoms (Long Covid) in survivors, in the first year after admission. In the study, we summarized the first three waves (spring -20, autumn 20 and spring 21), and found that the mortality rate was significantly higher in autumn 2020 (30%). We also saw that the use of mask treatment increased beyond the pandemic, and that the length of stay decreased. The second part of the study consisted of following up all those who survived intensive care, throughout the first year. The response rate is somewhere between 50-60% on this data, which is relatively good in a follow-up study. We have examined the level of post-traumatic stress symptoms after 6 months from the first wave, and it may appear that this level is no higher than we have previously seen in other intensive care patients, the same applies to anxiety and depression. In contrast, it may appear that a fairly high number reported some form of reduced cognitive function such as concentration problems, and here the basis for comparison is somewhat weaker from other populations. We are now in the process of investigating the occurrence of fatigue for the entire sample.",,2022,OSLO UNIVERSITETSSYKEHUS HF,296310.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P29212,312715,COVID-19 Supply Chain Research Group - MIA Task Force,"COVID-19 caused immediate problems for medicine supply worldwide and exposed the full-scale vulnerability of these supply chains. The pressure on supply chains was not limited to infection control equipment, tests or ventilators. It spread to other critical goods, including generic drugs. Medicine shortages were already a growing global problem in normal times before the pandemic. Now we see increased interest from the authorities in the vulnerabilities and the level of preparedness. But the many stakeholders have different goals and incentives when it comes to the focus on costs, quality, service and sustainable solutions. The supply chains are complex with many actors involved, they are global and vulnerable due to specialization and 'slimming' (few buffers) in the chains and moving production to low-cost countries. The project COVID-19 MIA Task Force has studied how the corona virus affected the chains and evaluated the effects of a number of measures to improve security of supply. We have studied the availability of paracetamol in seven countries, medicines for chronic disease and vaccination in Ethiopia, ventilators in three European countries and testing equipment for COVID-19 in Norway. None of the countries experienced a shortage of paracetamol and our study indicates how this was avoided through the decision-makers' rapid adjustment to a new situation when the pandemic hit. Ethiopia experienced more shortages except for paracetamol. One reason for this may be their own production of this medicine, and we are looking into this more closely now. Much data was collected despite the challenges of the pandemic and the conflict in Ethiopia. In addition, we have published a conceptual study of the importance of collaboration on resources in managing risk in supply chains and an empirical study of how MSF handled its response to the pandemic through modularization and standardization. The project has combined knowledge from supply chain management (SCM) with public global health and pharmacy, to contribute data decision support and tools to the decision makers. Together with partners from the Institute of Public Health (FHI), Jimma University, Institute of Health (JUIH) and St. Paul's Hospital Millennium Medical College (SPHMMC) in Ethiopia, BI Business School takes a systems approach to these supply chains. This means that we use tools that can simulate and contribute to the understanding of these complex systems and both the direct and indirect consequences of measures. All the sub-projects were carried out in collaboration between two or more partners, and combined different research methods and qualitative and quantitative data with modeling such as simulation and optimization. Pedagogical tools have been developed based on the results and the analytical models to be used in teaching and discussion with stakeholders. The results include many seminars, workshops, presentations and reports, podcasts and blogs, popularized articles, 3 master theses and tools in addition to six peer-reviewed articles. We develop modules for master's education in pharmacy. In total, the project has 56 results, most publicly available, see The MIA Project | BI.",,2023,STIFTELSEN HANDELSHØYSKOLEN BI,332175.62,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research","Policy research and interventions | Indirect health impacts | Health service delivery | Medicines, vaccines & other technologies",2020 +P29217,318837,ACTIvation robot to support rehabilitation at coVID-19,"This small collaborative project, ACTIVID, focuses on investigating the need for an activation service for older adults based on the activation and rehabilitation robot Berntsen, Co-create new functionalities and develop a unique activation service for older adults that can be deployed on a large- scale, in Norway, Denmark and the Netherlands. The investigation will include the need for Berntsen in the light of COVID-19 recovery.",,,INNOCOM AS,5656.94,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,Health Systems Research,Health service delivery,2020 +P29219,300867,MIA - Measures for Improved Availability of medicines and vaccines,"COVID-19 caused immediate problems for medicine supply worldwide and exposed the full-scale vulnerability of these supply chains. Medicine shortages were already a growing global problem in normal times before the pandemic, especially medicines that are no longer on patent (generic). When supply chains for medicines break down, it can have serious consequences in the form of illness and, in the worst case, death. Despite the fact that policy makers in many countries had discussed strategies to deal with the problem, few measures had been put in place by the time the pandemic was upon us. Now we see increased interest from the authorities in the vulnerabilities and the level of preparedness. But the many stakeholders have different goals and incentives when it comes to the focus on costs, quality, service and sustainable solutions. The supply chains are complex with many actors involved, they are global and vulnerable due to specialization and 'slimming' (few buffers) in the chains and moving production to low-cost countries. The focus on low prices for generic medicines has reduced public expenditure and enabled more people to buy them, but has also resulted in fewer manufacturers of many medicines. This, in addition to a lack of transparency and information sharing, means that 'fixing' the causes of the problems is easier said than done. The project combines knowledge from supply chain management (SCM) with public global health, pharmacy and health economics to contribute to the decision makers with data, decision support and tools. Together with partners from the Institute of Public Health (FHI), INSEAD Business School in France, Lancaster University in Great Britain, RSM and Jimma (Ethiopia), BI takes a systems approach to the chains. We contribute with knowledge of the types of solutions used to avoid shortages in (ab)normal times and the decision-makers' role in selection and implementation. We have brought the authorities' perspective into OSCM and vice versa and have demonstrated the need for an interdisciplinary approach to medicine shortages. We have contributed insights on how to prepare drug and medical device supply chains for future epidemics in the long term and presented practical conclusions and implications for decision makers. A key finding is the need to combine preparedness with adaptability through modular processes; resource linkages across sectors and disciplines; the interaction between temporary and permanent organisation, and combining risk management strategies. The decision makers can use our frameworks, tools and findings to improve the availability of generics in (ab)normal times The first peer-reviewed article was published in 2021 where we present a research agenda for applying theory in supply chains and logistics (OSCM) to the problem of drug shortages. During 2022-2023, we have published a further 13 articles. The results demonstrate and quantify how cooperation between countries on sharing tests during the early stages of COVID-19 would have helped to flatten the curve. We have quantified and illustrated the direct and indirect short- and long-term consequences of decisions to reduce medicine shortages, and show that decisions taken to reduce shortages can have the opposite effect in the longer term. We have studied and are studying different types of medication such as paracetamol and antibiotics. Ongoing research includes sub-projects on the consequences of setting environmental requirements in the procurement of medicines, cost-effectiveness in implementing emergency stocks for critical medicines, and how contracts should be set up to reduce shortages. All sub-projects are set up in collaboration between two or more partners, combining different research methods and qualitative and quantitative data with modeling such as simulation and optimization. Pedagogical tools are developed based on the results and the analytical models to be used in teaching and discussion with stakeholders. As of now, the results include many seminars, workshops, presentations and reports, podcasts and blogs, popularized articles, 15 master theses and tools in addition to the peer-reviewed articles. We develop modules for master's education in pharmacy. In total, the project has so far produced 137 results, most of which are publicly available, see The MIA Project | BI.",,2024,STIFTELSEN HANDELSHØYSKOLEN BI,1354271.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation | Vaccines research, development and implementation | Health Systems Research","Therapeutics logistics and supply chains and distribution strategies | Vaccine logistics and supply chains and distribution strategies | Medicines, vaccines & other technologies",2020 +P29222,322942,Contribution to NordForsk's call for Nordic health data research project on COVID-19,,,,NORDFORSK,598617.57,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,,,2020 +P29223,309571,Rapid Response Communication for Greenhouse Gas Budget Verification,"The Horizon 2020 project ""Observation-based system for monitoring and verification of greenhouse gases"" (VERIFY) aimed to develop scientifically robust methods to assess the accuracy and potential biases of national greenhouse gas emissions reported by countries through an independent pre-operational framework. The aim of RapidVERIFY has been to translate the scientific material from VERIFY into an accessible format that is relevant for Norwegian users and to communicate it continuously to the users. The material should primarily be short and focused, ranging from articles (blogs, fact sheets, opinion content), short video content, presentations, as well as social and traditional media activity. With COVID from early 2020, the plans had to be changed somewhat, and the main project VERIFY was also extended to 31 July 2022. In response to COVID-19, a paper was published in Nature Climate Change (Le Quéré et al 2020) under the VERIFY project on reductions in carbon dioxide emissions due to COVID-19 measures. In July 2020, the global methane budget was published in Earth System Science Data (Saunois et al 2020). And the global nitrogen oxide budget was published in Nature in October 2020 (Tian et al 2020). The Global Carbon Budget was published in December 2020 (Friedlingstein et al., 2020). In 2021, a commentary was published in Nature Climate Change which updated the understanding of the corona pandemic's effect on emissions during 2020 (Le Quere et al 2021). Due to the corona pandemic, the format of some of the communication activities was changed. A Norwegian report 'Main figures and data from the Global Carbon Project' was written and published by the Norwegian Climate Foundation and financed through the project. UiB led the development of a video for a wide audience about the ocean's carbon cycle, with imminent release (August 2022). The Global Carbon Budget 2021 was presented in March 2022, one of the first physical meetings after the Corona period. This was well attended with presentations on the global picture, and with more detailed presentations on China and India. Based on the work with methane and nitrous oxide, a blog post was written about the methane lift, and a CIENS breakfast seminar was organized in April, with researchers from both NILU and CICERO. Throughout the project period, several presentations have also been held throughout 2021 and 2022 for public agencies and a wider audience.",,2022,CICERO SENTER FOR KLIMAFORSKNING,113138.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P29226,302079,Immunological disease mechanisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME),"Chronic fatigue syndrome/myalgic encephalomyelopathy (CFS/ME) is a common and disabling disorder characterized by fatigue, exertional malaise, pain and other symptoms. The underlying disease mechanisms are still incompletely understood, despite significant research efforts in recent years. The immune system (which protects us against infections) is moderately disturbed in CFS/ME, but it is unclear whether this disturbance is the cause of the patients' symptoms. This project involves a detailed mapping of the immune system in CFS/ME patients, with particular focus on two elements: the inflammatory reaction and the function of the B cells (which are a specific type of white blood cell). Furthermore, we plan to study the connection between immune disorders, hormonal/neurological disorders and symptoms. The main data source is the international COFFI consortium (Collaborative on Fatigue Following Infection), which disposes of data from 18 post-infectious cohort studies (i.e. studies that have focused on the development of CFS/ME in the wake of ""kissing sickness"", COVID-19 and other infections ). The COFFI consortium includes more than 22,000 participants in 7 countries, ensuring a homogeneous patient population. Some patients with a post-COVID-19 condition (often referred to as ""Long COVID"") also fulfill diagnostic criteria for CFS/ME. There is generally very little knowledge about this patient group. Because this project was established just before/during the COVID-19 pandemic, we have so far focused on patients who have developed CFS/ME in the wake of COVID-19. We have published/submitted several scientific articles on immunological mechanisms in adolescents/young adults with COVID-19/Long COVID, and are now working (autumn 2023) to analyze the responses from advanced immunological experiments on white blood cells from this patient group.",,2024,AKERSHUS UNIVERSITETSSYKEHUS HF,1349067.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis | Post acute and long term health consequences,2020 +P29231,296083,FoodPilotPlant Norway: Upgrading of the Pilot Plant Facilities for Food Processing at Campus Ås (phase II),"FoodPilotPlant Norway (Matpiloten) is a research infrastructure for food processing located at NMBU and Nofima on Campus Ås. The infrastructure has been built up through the participating institutions' own efforts and the allocation of infrastructure funds from the Research Council of Norway. FoodPilotPlant Norway has had two awards from the Research Council of Norway, Phase I from 2011 to 2015 was awarded NOK 29 million and Phase II (current project) started in 2020 was awarded NOK 49 million. Up to now, NOK 26 million of the funds allocated in Phase II have been invested in new equipment, and more equipment is on the way. The project is to be completed in the first quarter of 2025. The infrastructure is in operation based on Phase I. The allocation of the infrastructure grants from the Research Council of Norway gives us the opportunity to develop a state-of-the-art pilot facility on Campus Ås, and this makes us an outstanding arena for research into food production and food processing. The infrastructure has made it possible for Campus Ås to expand its research opportunities, both with regard to food processing, the development of new food products and research into food safety. FoodPilotPlant Norge has thus made it possible for us to apply for and receive funding for new and innovative research projects. FoodPilotPlant Norway has infrastructure and equipment designed for research, innovation and teaching within the processing of all food raw materials, as well as residual raw materials from this processing. The infrastructure has equipment for the production of foodstuffs on a small scale, such as breakfast cereals, beer, cheese and sausages, tanks for fermentation, packaging and to investigate the growth of pathogenic microorganisms in processed food. Increased research focus on sustainability means that we have increased focus on implementing infrastructure to be able to utilize all the raw materials and use green technology when we produce food. The infrastructure also has access to laboratories with a wide range of analytical equipment. FoodPilotPlant Norway has a wide range of applications and the infrastructure is used in international and national research projects, in teaching and for testing processes and production of test products for the food industry. FoodPilotPlant Norway is used by students in Food Science both in regular teaching in the form of exercises, but also in master's and PhD work. In 2022, both researchers from universities, research institutes and industry as well as bachelor and master students have used the infrastructure in FoodPilotPlant Norway, in total the infrastructure has had 400 users in 2022. The infrastructure is currently a research base for 15 PhD students. The infrastructure is used for external courses run by e.g. The ecology program under the auspices of the Norwegian Directorate of Agriculture and the Competence Network for small-scale food production. This has been somewhat reduced in the spring of 2022 due to the COVID shutdown, but has picked up during the autumn of 2022. In 2022, 9 scientific articles based on activity in FoodPilotPlant Norway were published in international scientific journals. FoodPilotPlant Norway also has regular publications in the media and popular scientific journals. There are currently > 100 research projects at Campus Ås that use FoodPilotPlant Norway's research. These projects work, for example, with: - To develop meat substitutes made from beans that can be used e.g. in burgers. - Norwegian tapas cheese made from goat's milk, and the importance of somatic cells in the milk for cheese quality. - Food quality when new raw materials such as yeast grown from tree sugar, insects, seaweed and kelp are used. - How molecules fluctuate in the food in order to be able to measure which types of fat, which types of proteins and how much of each fat and protein type you have in a food and thus improve the utilization of the raw materials. - How chicken offal can be used to produce bacteria or yeast, which can then be used for, for example, oil or new food ingredients. - To develop more environmentally friendly packaging that also extends the shelf life of food products. - Develop new ways to secure the food against the growth of unwanted bacteria and thus give increased durability and better taste to the food. Operations in 2020, 21 and 22 have been strongly affected by COVID 19, where NMBU in particular but also partly Nofima have been shut down for parts of the year. Use and utilization of the infrastructure has therefore been much lower than expected in these years.",,2027,"NORGES MILJØ- OG BIOVITENSKAPELIGE UNIVERSITET (NMBU), FAKULTET FOR KJEMI, BIOTEKNOLOGI OG MATVITENSKAP",5430664.04,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Research Council of Norway (RCN),Norway,Europe,Europe,Unspecified,,,,Norway,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P29236,GA203580,Development of a defective interfering RNA based antiviral approach to treat infections by SARS-CoV-2 and emerging variants,"Specific therapy for severe disease caused by SARS-CoV-2 is limited. The ability of viruses to become resistant to a therapy may be obstacle for antiviral development. This project develops a unique platform, using virus-specific antiviral RNA, as a unique and possibly “antiviral-resistance” proof approach that could be deployed as a therapeutic for COVID-19 and also help to solve the challenge of viral pandemics from known and unknown viruses, especially other human pathogenic coronaviruses.",,2025,The Council of the Queensland Institute of Medical Research,587934.51,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,Innovation,,,Australia,Australia,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P29237,GA58835,Harnessing universal immunity to influenza,"Prof Kedzierska's work combines cutting-edge basic research with unique clinical studies to define how to generate protective immunity against the pandemic and newly emerged influenza viruses. This research will identify key factors that drive the severe and fatal influenza disease in high-risk groups, including the young, elderly, pregnant women and Indigenous Australians. Findings on the optimal human immunity to influenza viruses will be applicable to other infectious diseases and tumours.",,2024,University of Melbourne,1730837.39,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years) | Infants (1 month to 1 year) | Newborns (birth to 1 month) | Older adults (65 and older),Unspecified,Indigenous People | Women,Unspecified,Clinical,Unspecified,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management",Immunity | Disease susceptibility | Prognostic factors for disease severity,2020 +P29238,GA58839,Advancing influenza vaccines for broad and durable protection,"Current influenza vaccines elicit poor protection against viruses undergoing rapid change. This proposal will define the potential for protective, cross-reactive antibody responses in humans and use this information to identify conserved sites of vulnerability on the hemagglutinin of influenza viruses. This will inform the development and assessment of novel influenza vaccine concepts in animal models of human influenza infection.",,2024,University of Melbourne,419910.87,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P29239,GA58870,Translating virus biology and host immunity for influenza control,"Flu epidemics occur every year but some seasons, like 2017, are more severe than others. Vaccines are the most effective way to prevent flu but they are not always effective. Flu pandemics occur a few times each century, when new influenza viruses emerge from animal hosts, infect people and spread around the world. This research will examine human and animal influenza viruses and immunity to flu infection and vaccines, to improve seasonal flu vaccines and better prepare for future pandemics.",,2024,University of Melbourne,1255026.26,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +P29240,GA216978,Harnessing the beneficial off-target effects of BCG vaccination to boost protection against SARS-CoV-2,"Bacillus Calmetteâ€""Guérin(BCG), the vaccine that protects against tuberculosis, also protects against other diseases. This is thought to be because BCG can boost immunity. We will investigate how BCG boosts immune responses to SARS-CoV-2 and if this improves protection against COVID-19 and the effectiveness of COVID-19 vaccines. We will combine use of mouse models with use of samples from BRACE, our 6800 participant trial testing if BCG vaccination protects against COVID-19 in healthcare workers.",,2025,Murdoch Childrens Research Institute,870639.49,Animals | Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +P29241,GA202709,COMBAT - A Combination B-and T-Cell Epitope Vaccine to Futureproof COVID-19 Vaccine,"We are proposing a vaccine that contains only safe components of the SARS-CoV-2 virus, yet effectively elicits protective immunity. The vaccine works by inducing antibodies capable of preventing the virus from attaching to lung cells, and killer T cells that destroy virus-infected cells. This highly innovative approach will generate a much needed safe and prophylactic 2nd generation modular vaccine, ideal for “vaccine update” that will have a major impact on health and society more generally.",,2025,Griffith University,873396.17,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Vaccines research, development and implementation",,2022 +P29242,GA204244,Targeting neuropilin in SARS-Cov-2 neuronal uptake and transport,"COVID-19 is associated with a variety of neurological symptoms, ranging from a transient loss of smell and taste to headaches to severe ischaemic damage in fatal cases. The long-term consequences of potential interactions of the causative virus, SARS-CoV-2, with brain cells are currently unknown but could be linked to intractable neuronal degeneration as previously found with the 1918 influenza pandemic. We will investigate the uptake and transport of the virus and find ways to block infection.",,2025,The University of Queensland,652185.66,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P29243,GA204228,Defining the impact of chronic lung disease on COVID-19 and developing effective therapies,"COVID-19 disease is driven by virus-induced, hyper-inflammation that damages the lungs. Patients with chronic lung disease, such as chronic obstructive pulmonary disease (COPD) and tuberculosis (TB), have increased severity of COVID-19 disease. Using our models of TB and smoking-induced COPD, we will define how chronic lung disease increases the severity of COVID-19, how CoV2 infection exacerbates TB and COPD, and identify effective drugs that suppress this inflammatory damage to the lung.",,2025,University of Sydney,646759.51,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Health and Medical Research Council (NHMRC),Australia,Western Pacific,Western Pacific,Western Pacific,,,,Australia,Australia,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2022 +P29244,COV20_00286,Efficacy of hydroxychloroquine in preventing infection and reducing viral load and disease severity in SARS-CoV-2 infected pregnant women in Spain,"It is unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes. This will be a randomized, double blinded, placebo-equivalent controlled multicentre trial aiming to assess the effect of hydroxychloroquine (HCQ) in reducing maternal viral load and the efficacy of HCQ to prevent incident SARS-CoV-2 infection. Pregnant women of any gestational age, parity and age, undergoing pre-natal follow up at four maternity hospitals with a positive PCR test, or who are contacts of a confirmed case, will be recruited and randomised 1:1 to receive HCQ orally (400 mg/day for 3 days, followed by 200 mg/day for 11 days) or ascorbic acid orally (500 mg for 3 days, then 250 mg/day for 11 days). Women will be followed up for the duration of the intervention when PCR tests for SARS-CoV-2 will be repeated, and up to delivery, when the pregnancy outcome will be registered, a cord blood sample and a neonatal throat swab will be collected after birth to be tested for SARS-CoV-2",,-99,FUNDACION PRIVADA INSTITUTO DE SALUD GLOBAL BARCELONA (ISGLOBAL),,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,,,,Spain,Spain,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Prophylactic use of treatments | Clinical trial (unspecified trial phase),2020 +P29245,COV20_00144,Transmisión de SARS-CoV2 por el aire: detección en hospitales y tecnologías innovadoras,"There are currently no effective methodologies to detect viruses in the air. Our group has recently optimized filter-based methods capable of retaining the entire airborne virus community. SARS-CoV2 is stable in the air for at least 3 hours and is very effective in transmission, but its airborne spread has not been studied. We propose to use this methodology to detect SARS-CoV2 in hospitals and carry out a longitudinal study of the prevalence of the virus in hospital spaces. In parallel, we will develop nanoparticles as simple colorimetric detection methods, applicable to hospitals, to quickly monitor the presence of viruses captured in the air. We will develop laser-induced fluorescence (LIF) sensors as a method of direct detection of SARS-CoV2 particles and other viruses in the air, without the need to process the samples",,-99,"AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS, M.P.",,Environment | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Innovation,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Diagnostics | Disease transmission dynamics,2020 +P29246,COV20_01036,SARS-COV-2 diagnosis by phi29 polymerase amplification,"The project aims the validation of a reliable method for diagnosis of SARS-COV-2 infection. This novel method will allow the improved detection of the viral RNA molecule by means of a virus-specific linear probe that becomes circularized only in the presence of the viral RNA. Once the probe becomes circular, an engineered form of phi29 DNA polymerase (CSIC patent licensed to 4basebio) will start copying the circular template by generating an unlimited synthesis reaction defined as ""rolling-circle replication"" (RCR), which depends on the unique and robust strand-displacement synthesis capacity of this phi29 DNA polymerase variant. This peculiar mode of synthesis, a hallmark of the isothermal DNA amplification of full genomes used worldwide, could be easily detected as a readout of the presence of SARS-COV-2 genomic RNA",,-99,FUNDACIÓN DEL SECTOR PÚBLICO ESTATAL CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS CARLOS III,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Innovation,,,Spain,Spain,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29247,COV20/01314,Registro Estatal de COVID‐19: The Spanish COVID‐19 Data portal,"The State COVID-19 Registry has been designed to 1) facilitate the integrated collection of data related to COVID-19 from the National Health System, by defining a set of commonly used standards and providing mechanisms for collection and their storage. In a first phase, it will integrate data from projects financed by the ISCIII COVID 19 FUND, and in a second phase it will open to the integration of other projects, initiatives and databases; 2) provide the necessary technical infrastructure for the development of a platform dedicated to the integrated analysis of molecular, clinical and epidemiological data that results in the improvement of disease management protocols; 3) establish the necessary coordination channels with equivalent initiatives at the European and International level, respecting the framework established in current regulations regarding the handling of sensitive data.",,-99,Centro Nacional de Supercomputación (BSC‐CNS),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,National Institute of Health Carlos III [El Instituto de Salud Carlos III] (ISCIII),Spain,Europe,Europe,Europe,Data Management and Data Sharing,,,Spain,Spain,Health Systems Research,Health information systems,2020 +P29248,216455,Study of the role of oxylipins in the occurrence of severe forms of COVID-19: VARIANCE,"About Sorry, this entry is only available in FR.",,-99,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity,2024 +P29249,157819,Longitudinal follow-up of a population cohort in a French city with high SARS-CoV-2 circulation in early 2020: the COVID-Oise cohort,"About (Last update: 10/10/2023) Context In early 2020, the first French death attributed to the SARS-CoV-2 virus was a teacher from Crépy-en-Valois, a city north of Paris. The intense circulation of the novel coronavirus in that area was confirmed by sero-epidemiological studies conducted by the Institut Pasteur among pupils, their families, teachers and non-teaching staffs (Fontanet et al.). Intense SARS-CoV-2 circulation during that period was also identified within the Crépy-en-Valois local hospital and nursing homes by diagnostic campaigns conducted by the Amiens hospital among residents and staffs (unpublished data). Like The COVID-Oise project constituted a unique opportunity to follow a general population cohort within an area that was one of the first affected in Europe in early 2020, in order to better characterize the immunity specific to the SARS-CoV-2 virus. The nature and duration of this immunity, whether acquired following natural infection and/or vaccination, in the context of emerging variants of the virus, and the long-term consequences of the post-COVID syndrome (also called long COVID) are key elements of the COVID-19 research. Design The COVID-Oise cohort is constituted by participants across all age categories starting from 5 years-old, focusing on benign and asymptomatic COVID-19 forms that represent most of the clinical cases. Over a 2-year period, two sessions per year have well organized for clinical-epidemiological data collection and biological sampling. The last session took place in April 2022. Status 905 participants were enrolled in the COVID-Oise cohort, including 723 among families from the Crépy-en-Valois area, 107 staff members and 75 residents from the local hospital and nursing homes. 64.6% of the participants also participated in the initial studies conducted by Institut Pasteur or the Amiens hospital in early 2020, allowing for a follow-up since the beginning of the pandemic for almost two thirds of the COVID-Oise participants. 61.2% of the participants were infected at least once by the SARS-CoV-2 between January 2020 and the end of their follow-up within the study. After the last session in April 2022, SARS-CoV-2 specific antibodies were detectable in 96.2% of the collected blood samples, attesting for past infection(s) and/or vaccination(s) for almost all the study population. Several analyzes were run on the collected samples to study the humoral response following infection and/or vaccination. Research continues with a focus on additional topics, including characterization of some aspects of the SARS-CoV-2 specific cellular responses, immunity in the nasopharyngeal mucosa, and post-COVID syndrome. Results (from the initial studies conducted in early 2020, and from the COVID-Oise cohort) - At a time when serological tests were not yet commercialized, serological assays to detect SARS-CoV-2 specific antibodies were established by several teams within the Institut Pasteur based on sera from infected individuals from Crépy-en-Valois (Grzelak 2020). - These serological assays allowed to describe the early SARS-CoV-2 circulation within the high school and primary schools of Crépy-en-Valois. In April 2020, approximately 40% of high school students and teachers had already been infected by the emerging virus, with transmission occurring within their households (10% of parents and 12% of brothers and sisters of the high school students were seropositive). In primary schools, 23% of pupils in classes where the virus circulated with symptomatic children were seropositive, while only 6% were seropositive in classes where no symptoms were reported (Fontanet 2021). - Anosmia and ageusia were identified as predictive factors for COVID-19 early in the pandemic. These symptoms were particularly reported by women aged between 18 and 44 years old, and were associated with headaches and fatigue (Galmiche 2021). - In-depth analysis of antibody functions in sera from infected individuals showed that asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells through complement deposition and antibody-dependent cellular toxicity, but to a lower degree than symptomatic infection (Dufloo 2021). - Quantitative measurements of antibodies of different isotypes against several SARS-CoV-2 antigens within sera of infected individuals allowed accurate classification of time since infection into intervals of 0-3 months, 3-6 months, 6-12 months using machine learning algorithms. The ensuing computational method could be used to reconstruct past SARS-CoV-2 transmission when applied to samples from a single cross-sectional sero-prevalence survey (Pelleau 2021). - A focus on the nursing home residents who had received three doses of COVID-19 vaccine by the end of 2021 showed that this population at particular risk of severe forms of COVID-19 had developed antibodies capable of neutralizing the BA.1 Omicron variant of SARS-CoV-2. Nevertheless, some breakthrough infections were reported later on during the first Omicron wave in early 2022, arguing in favor of a fourth vaccine dose for the elderly (Bruel 2022). - The COVID-Oise cohort allowed for the description of the sero-epidemiology of seasonal coronaviruses that are responsible for recurrent diseases in children each year (De Thoisy 2023). - Protection against COVID-19 at the population-level was estimated by applying mathematical models on total SARS-CoV-2 antibody levels measured by serological tests. This methods could allow for identification of subgroups of under-protected individuals who would benefit from a vaccine booster dose (Woudenberg 2023). Partners Pasteur Institute: Medical Research Directorate; Clinical Research Coordination Office; Clinical investigation and biological resources platforms; numerous research units (see References). CHU Amiens: Biology-pharmacy department References - Grzelak L, et al. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci Transl Med. 2020 Sep 2;12(559):eabc3103. doi: 10.1126/scitranslmed.abc3103. Epub 2020 Aug 17. PMID: 32817357; PMCID: PMC7665313. - Fontanet A, et al. SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of ​​high transmission, France, January to April 2020. Euro Surveill. 2021 Apr;26(15). doi: 10.2807/1560-7917.ES.2021.26.15.2001695. PMID: 33860747. - Galmiche S, et al. Characteristics Associated with Olfactory and Taste Disorders in COVID-19. Neuroepidemiology. 2021;55(5):381-386. doi:10.1159/000517066. Epub 2021 Jul 1. PMID: 34198303; PMCID: PMC8339025. - Dufloo J, et al. Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies. Cell Rep Med. 2021 May 18;2(5):100275. doi: 10.1016/j.xcrm.2021.100275. Epub 2021 Apr 20. PMID: 33899033; PMCID: PMC8057765. - Pelleau S, et al. Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection. J Infect Dis. 2021 Nov 16;224(9):1489-1499. doi:10.1093/infdis/jiab375. PMID: 34282461; PMCID: PMC8420633. - Bruel T, et al. Neutralizing antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study. EClinicalMedicine. 2022 Jul 22;51:101576. doi: 10.1016/j.eclinm.2022.101576. PMID: 35891947; PMCID: PMC9307278. - De Thoisy A, et al. Seroepidemiology of the Seasonal Human Coronaviruses NL63, 229E, OC43 and HKU1 in France. Open Forum Infect Dis. 2023 Jul 3;10(7):ofad340. doi:10.1093/ofid/ofad340. PMID: 37496603; PMCID: PMC10368309. - Woudenberg T, et al. Estimated protection against COVID-19 based on predicted neutralization titers from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021. Euro Surveill. 2023 Jun;28(25):2200681. doi: 10.2807/1560-7917.ES.2023.28.25.2200681. PMID: 37347417; PMCID: PMC10288827.",,-99,N/A,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2020 +P29250,201529,COVID-AMR,"About COVID-AMR (Impacts of the COVID-19 pandemic on antibiotic resistance) Collaboration: Laura Temime (Cnam) The COVID-19 pandemic started in a context of global efforts to prevent and control antimicrobial resistance. It has led to a major disruption of the organization of care, antibiotic prescription, and the implementation of control and prevention strategies against the transmission of respiratory infections, all of which being key regulating or promoting factors of antimicrobial resistance spread in the community and in hospitals . Considering the pleiotropic effect of the pandemic, it is hard to predict how it has impacted the spread of antibiotic resistant bacteria both in the community and in health care settings. Better understanding this impact is crucial to improve care organization for future epidemics and pandemics of severe respiratory diseases and avoid side effects from a public health perspective. Community COVID-AMR. We develop mathematical models to jointly analyze the dynamics of resistant bacteria (with a specific focus on pneumococcus) and SARS-CoV-2 in the community and understand better the drivers and interactions that can lead to the observed trends of bacterial infections in 2020. Hospital COVID AMR. The aim of the project is to evaluate whether the burden in COVID-19 patients in hospitals during the first two years of the pandemic has changed the incidence of resistant infections in these settings. We analyze national surveillance data of COVID-19 cases and antibiotic resistance in hospitals that include more than 1,400 hospitals from the 1st of March 2020 to December 2021 using statistical models and mathematical models to identify the key mechanisms by which the pandemic may have affected antibiotic resistance bacteria transmission in these settings, as well as the level of resistance, and assess prevention and control strategies. Partners: Inserm National Conservatory of Arts and Crafts Pastor Institute Public Health France SPARES Funding: Labex IBEID, INSERM",,-99,N/A,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2021 +P29251,157824,"ComCor: Study of sociodemographic factors, behaviors and practices associated with SARS-CoV-2 infection","About The ComCor study is a nationwide case-control study which aims first to describe the locations and circumstances of recent SARS-CoV-2 infection, and second, to assess the role of different settings and activities in the acquisition of recent SARS-CoV-2 infection. Case recruitment via email from the National Health Insurance Agency in France began in October 2020 and has recruited over 160,000 participants to date. Controls are individuals recruited from the Ipsos market research database matched to cases by age, sex, region, population density and exposure period. The description of SARS-CoV-2 acquisition focuses on the demographic characteristics of cases, the reasons for testing, their adherence to infection prevention and control measures and isolation, and the circumstances of infection. In the first descriptive analysis of the first 77,000 recruited cases up to January 2021, half of the participants knew the person who infected them: predominantly someone in the a household (42%), followed by an extended family member (21%), someone in the work setting (15%), friends (11%) or another setting (11%). Private gatherings with extended family and friends, and working in shared offices, were found to be the most common circumstances of transmission. For 37% of cases infected outside the household, the suspected source of infection was reported to be symptomatic at the time of transmission. This increased to 46% when infection occurred in the workplace. Adherence to isolation was greater when someone had been infected by another person outside the household, but participants often began isolation only after the results of testing had been received, rather than from the onset of symptoms. In an analysis of more than 10,000 single interactions that led to infection outside the household, infection most frequently occurred in indoor settings with closed windows (80% of cases), followed by indoor settings with open windows (15%), and outdoor settings ( 5%). In the case-control study, controls complete the same questionnaire of sociodemographic factors, behaviors and recent activities as cases, to identify factors associated with recent SARS-CoV-2 infection. In the first analysis of 3426 cases (with symptom onset between 30 September and 23 November 2020) and 1713 controls, we found an increased risk of infection associated with any additional person living in the household (+16%); having children attend daycare (+31%), kindergarten (+27%), middle school (+30%), or high school (+18%); attending professional (+15%) or private gatherings (57%); having recently frequented bars and restaurants (+95%), or having practiced indoor sports activities (+36%). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, with the exception of informal carpooling (+47%). The risk of infection varied by occupation, but remote working was associated with a decreased risk of infection (-35%). Publications First report (December 2020) https://www.pasteur.fr/fr/espace-presse/documents-presse/etude-comcor-lieux-contamination-au-sars-cov-2-ou-francais-s-infectent- they Intermediate report (March 2021) https://hal-pasteur.archives-ouvertes.fr/pasteur-03155847 Funding REACTing Foundation of France",,2022,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease transmission dynamics | Disease susceptibility | Approaches to public health interventions,2020 +P29252,172440,Towards understanding of immunostimulatory properties of SARS-CoV-2 RNAs,"About Summary COVID-19 represents a massive health threat for humans and has already caused huge economic problems all over the world. Profound knowledge of SARS-CoV-2 interaction with the host and the host immune response are needed to control this virus and to readjust antiviral therapy currently used to treat COVID-19. The first line of defense against viral infections is antiviral innate immunity. The host pattern recognition receptors (PRRs) detect specific molecular patterns exclusively found in pathogens and initiate the adequate immune response. Among them, the RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) and zinc finger antiviral proteins (ZAP) are ubiquitously expressed RNA binding proteins that detect viral RNA in the cytosol to initiate innate antiviral responses and restrict viral replication. The main objective of SARS-Cov-2immunRNAs is to bring immunostimulatory SARS-CoV-2 RNAs and their detection by PRRs into the spotlight as an important component of the innate immune response to the virus that predetermines the outcome of viral infection. For this we will: i) determine specific RNA signatures of SARS-CoV-2 on PRRs, such as RIG-I, MDA5, LGP2 and ZAP; ii) obtain a comparative view on dinucleotide biases, primary/secondary and ternary structures for PRR-specific biological SARS-CoV-2 RNA ligands; iii) validate and compare immunostimulatory properties (adequate or detrimental) of novel PRR-specific SARS-CoV-2 RNA ligands. Our hypothesis is that detrimental activation of PRRs by immunostimulatory SARS-CoV-2 RNA ligands could explain an early robust host immune response underlying the severity of pneumonia and the infection outcome of COVID-19. In-depth knowledge of SARS-CoV-2 RNA immunostimulatory potential will help in understanding of how to induce protective innate antiviral immune responses to this virus and to interfere with detrimental innate immune responses. Additionally, SARS-CoV-2 immunostimulatory viral ligands will also provide new potential adjuvants for vaccines or components of prophylactic vaccines. Collaboration Andrea Di Gioacchino and Simona Cocco from Physics Laboratory of the Ecole Normale Supérieure, PSL & CNRS UMR8063, Sorbonne University, University of Paris Funding SARS-Cov-2 immunRNAs - AAP FLASH COVID-1 CoV-2Sensing - Institut Pasteur call for projects",,-99,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P29253,186244,SACADA - Transmission of SARS-CoV-2 in Food Preparation Workshops - Focus on meat processing workshops,"In France and around the world, during the COVID-19 pandemic, agri-food workers are considered part of the essential workforce of critical infrastructure, from farmers to processing plant employees, truck drivers, and supermarket cashiers. In addition, in some countries such as the United States, by presidential decree, meat and poultry processing plants must continue to operate to avoid disrupting the food supply chain. Workers in these industries may be more exposed to coronaviruses because telework is not possible, and many face increased risks due to the proximity of their work environment. The issue of virus circulation in meat processing plants in France needs to be carefully addressed from three perspectives: (i) protecting workers and preventing these premises from becoming hotspots for virus circulation in communities; (ii) preventing the closure of these processing plants and ensuring supplies; and (iii) prevention of food contamination to avoid the exportation of this virus to other places. The objective of this project is to understand the circulation of SARS-CoV-2 in meat processing plants in order to provide prevention or risk reduction measures for workers and consumers. We plan to gather/collect the data needed to understand the circulation of the virus in this type of workplace and use them to build a simulation model of the spread of SARS-CoV-2. The project is organized into four tasks. The transmission of SARS-CoV-2 and persistence factors in meat processing plants will be studied (WP1). The objectives will be to conduct an in-depth literature review on SARS-CoV-2 transmission parameters in order to extract relevant data to study its circulation, and to define laboratory protocols to fill the data gaps or uncertainties on certain parameters. Then, a description of the working conditions and environmental factors in these factories will be carried out, through questionnaires and interviews as well as observations to be carried out within the factories (WP2). The data collected will be used to define the parameters of the laboratory experiments. These data will also be used to feed the mathematical model that will be developed to simulate the spread of the virus in a meat processing factory (WP3). It will be used to evaluate the impact of certain management measures or reduction of the probability of transmission of the virus to employees, and the contamination of products and the environment. This model will also allow us to explore the transmission of the virus outside the factories. Finally, different communication tools will be proposed (WP4), essential to engage employees in an effective safety management policy, obtain their cooperation and support, and maintain a positive safety culture. The impacts of this project will be 1) to increase knowledge on the transmission of the virus in a professional setting; 2) to provide solutions to companies to better calibrate their preventive measures and mitigate risks in the event of the introduction of the virus into their premises; 3) to provide data on the transmission modalities and simulate the circulation of the virus under different scenarios; and 4) to provide decision support for companies and governments based on available science and data. The approach is extensible to other situations: processing plants, offices, universities, public places, etc. Our team will participate in the collection and generation of data on the persistence of SARS-CoV-2 on the different surfaces that can be found in meat cutting workshops, in order to feed the model.",,-99,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease transmission dynamics | Impact/ effectiveness of control measures | Approaches to public health interventions | Communication,2021 +P29254,202813,COVID-19-popCell - Genetic and infectious factors underlying population variability in immune responses to SARS-CoV-2,"About The popCell project aims to characterize the variation in immune response to SARS-CoV-2 of peripheral blood mononuclear cells (PBMCs) from > 200 adults, healthy volunteers of West European, Central African and East Asian origin, (EvoImmunoPop and SeroPrevHK-CoV- 19 cohorts). In this project, we have acquired single-cell transcriptional profiles (scRNA-seq) of >1M PBMCs following stimulation by SARS-CoV-2, Influenza A virus (IAV) or mock controls, in order to analyze the differences in immune response to SARS-CoV-2 among human populations worldwide. In addition, all donors were genotyped at >2.5 M sites using the Omni5 Illumina BeadChip, allowing to perform eQTL mapping and to define the role of genetics in these differences. These data will be integrated with chromatin accessibility data (scATAC-seq) and viral serologies (VIRscan) obtained in the basal state to identify regulatory regions that respond to environmental stimuli and contribute to the priming of immune responses to SARS-CoV-2. Any reanalysis of data published as part of the COVID-19 popCell project are listed below, together with the aim of the reanalysis and name of the person responsible for the data. List of data reuse: TBD",,2026,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P29255,198723,CoVariant - Understanding the determinants of mucosal immunity and optimizing the diagnosis of infection with SARS-CoV-2 variants,"What are the objectives of this study? This study aims to improve the identification of SARS-CoV-2 infection as well as to better understand the immune response of infected people, particularly at the level of the respiratory mucosa. To do this, researchers need to collect nasal and nasopharyngeal swabs, blood, saliva and exhaled air samples. People are identified via the project's partner medical analysis laboratories, pharmacies and health centers carrying out COVID-19 screening tests. Who can participate? The persons concerned must: be over 18 years old have carried out a COVID test ≤ 4 days reside in Ile de France and can travel to the Institut Pasteur (Paris 15th), have a weight of at least 50 kg benefit from a Social Security system with the exception of State Medical Aid What does participation in the study involve? The CoVariant study is taking place at the ICAReB-Clin platform of the Institut Pasteur (Paris 15th). Participants not infected with SARS-CoV-2: 2 visits to be carried out according to the following schedule: The 1st visit (1 hour inclusion visit) will take place a maximum of 4 days after the test and will include a clinical examination, blood, saliva and nasopharyngeal samples and a collection of exhaled air. A 2nd visit (30 min) will take place a maximum of 3 months after inclusion and will include a clinical examination, blood and nasopharyngeal samples and collection of exhaled air. Participation in the study is for a maximum of 3 months. For participants infected with SARS-CoV-2: 4 visits to be carried out according to the following schedule: The 1st visit (1 hour inclusion visit) will take place either at the Institut Pasteur or at home if isolation is required. This visit will include a clinical examination, blood, saliva and nasopharyngeal samples and a collection of exhaled air. The following 3 visits (30 min follow-up visits) will take place 1 week, 1 month then 3 months after the inclusion visit. These visits will include a clinical examination, blood, saliva and nasopharyngeal samples and a collection of exhaled air. Participation in the study is 3 months. Participation compensation: A fixed compensation of €30 will be paid at the end of each visit to the Institut Pasteur. 2 methods of recruiting participants: - 1. Have you performed a COVID test in a Biogroup laboratory? - If you do not object to the analysis laboratory, your telephone details will be transferred to the CoVariant team at the Institut Pasteur. You have the right to refuse that these are transmitted and you can change your mind at any time thereafter, without having to give a reason. If your contact details are provided, a member of the CoVariant team will call you to: present the study to you, check if you can participate obtain your oral agreement to participate offer you an appointment for the inclusion visit within 4 days following your COVID test. By clicking on the links below you will have access to the complete information notices which you must read before agreeing to participate in this study. For infected people For uninfected people - 2. Have you performed a COVID test in a laboratory (non-Biogroup), a pharmacy or in a health center? - If you are interested in participating in the CoVariant study you can contact the ICAReB-Clin platform at the following address: Covariant@pasteur.fr. You have the right to refuse to participate or to change your mind at any time thereafter, without having to provide a reason. During your contact with the ICAReB-Clin platform, a member of the CoVariant team: will present the study to you, will check if you can participate will offer you an appointment for the inclusion visit within 4 days following your COVID test. By clicking on the links below you will have access to the complete information notices which you must read before agreeing to participate in this study. For infected people For uninfected people - 3. ICAReB-Clin offered you to participate in the study? - If the ICAReB-Clin platform has asked you to participate in the study and you are interested, a telephone interview will be carried out. You have the right to refuse to participate or to change your mind at any time thereafter, without having to provide a reason. During your contact with the ICAReB-Clin platform, a member of the CoVariant team: will present the study to you, will check if you can participate will offer you an appointment for the inclusion visit according to your availability",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Immunity | Disease pathogenesis | Supportive care, processes of care and management",2023 +P29256,157392,Humoral immunity & human monoclonal antibodies against SARS-CoV-2,"About The objective of this research project is to understand the molecular and functional basis of the memory B-cell antibody response to the SARS-CoV-2 Spike protein. One of the key goals of this research program is to make use of this knowledge to develop new therapeutic strategies, particularly immunotherapies using potent SARS-CoV-2 neutralizing antibodies that we anticipate isolating from infected donors who entered in remission.",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Pre-clinical studies",2021 +P29257,141769,SocialCov - SARS-CoV-2 contact survey,"About Click here to go to the survey Containment, barrier measures, limitation of gatherings, etc. The prevention measures currently put in place are unprecedented. They have fundamentally changed the contacts we have on a daily basis. However, it is precisely through these contacts that the virus is transmitted. To understand the evolution of SARS-Cov-2 transmission in the population, it is important to evaluate how our contacts change over time within our population. A first study carried out during confinement showed that this unprecedented measure had reduced contacts by more than 70% among the French. Today we are launching a new survey of the French population. Through questions like ""Did you have contact yesterday at your workplace?"" >> ""How old were your contacts yesterday during your leisure time?"" "", it will be possible to better understand the impact of current measures and the epidemic on our social and professional lives. Collecting this information on a large scale is essential to refine modeling in the context of the epidemic, and thus allow modelers to better understand and analyze the spread of the virus in France during this very special period. Your contribution is key. If you agree to participate and complete the questionnaire, you will be asked a certain number of personal questions: composition of your household, quantification of your contacts and lifestyle habits. This questionnaire is anonymous. Answering all the questions takes approximately 10 minutes. As several waves will be launched to ask you to respond to this survey, you are asked not to respond more than twice in the same month. Thank you in advance for your time and contribution! Click here to go to the survey The SocialCov survey is an Institut Pasteur / Paris Saclay / University of Versailles Saint Quentin / Inserm project Have you responded and want to contribute even more? You also have the opportunity to participate in monitoring the COVID-19 epidemic in the general population by joining COVIDnet.fr. To do this, you don't need to be sick, an email address is enough. Report detailing an analysis of data collected during the first wave below. [gview file=""https://research.pasteur.fr/wp-content/uploads/2020/04/research_pasteur-socialcov-enquete-contacts-sars-cov-2-report-public-socialcov-final-2.pdf ""]",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Disease surveillance & mapping | Restriction measures to prevent secondary transmission in communities | Approaches to public health interventions,2020 +P29258,155686,Restriction of SARS-CoV-2 replication by coding and non-coding genes in human and bat cells,"About Knowledge concerning the interaction of SARS-CoV-2 with human and bat cells is sparse. We will use state-of-the-art RNA-sequencing analysis, original bioinformatics tools, loss-of-function approaches and mechanistic studies to identify and characterize coding and non-coding genes that restrict viral replication in human and bat cells. Taking advantage of some of these naturally occurring viral inhibitors may be an effective strategy in the development of novel drugs to treat the disease.",,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2021 +P29259,144475,Identification of cellular PDZ-containing Proteins targeted by the SARS-Cov-2 virus during infection (PPCOVi),"About Thanks to their binding to PDZ domains, viral proteins play an important role in the replication and pathogenesis of SARS-CoV. Through cellular and in vitro high-throughput tests, this project aims to identify the cellular proteins that would be targeted by these viral proteins during infection and to characterize the mechanism by which viral sequences compete with cellular interactions through PDZ domains.",,-99,N/A,,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2020 +P29260,156743,Modeling SARS-CoV-2 infection and immune responses in humanized mouse models,About,,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P29261,157175,Assessing Population-Level Immunity to SARS-CoV-2 with Serological Assays,About,,-99,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P29262,141840,CORONABODIES,"About CORONABODIES: Production of SARS-CoV-2 nucleoprotein (N) and spike (S) recombinant antigens and generation of anti-N and anti-S nanobodies for diagnostic and therapeutic applications. SUMMARY We propose a joint effort to generate as rapidly as possible unique tools: (i) recombinant nucleoprotein (N) and spike (S) antigens of SARS-Cov-2 and (ii) nanobodies directed against these 2 proteins. These tools will be made available to pasteurian labs and our consortium will synergize to develop diagnostic and therapeutic applications: N- and S-based serological assays, nanobodies-based antigen detection assays and neutralizing and potentially broadly cross-reactive nanobodies against the S proteins of betacoronaviruses. Short introduction/Rationale The current COVID-19 epidemic requires rapid development of: Fast and reliable diagnostic assays of SARS-CoV-2 infection, which could be performed within minutes at any time and any place away from the bench, as well as specific and sensitive serological assays to monitor in near-real time the spread of the epidemic and help the implementation of mitigation measures, Very efficient therapeutic antivirals, based on a proven technology to reduce clinical development time. In that respect, the goal of our project is to produce as quickly as possible the required tools which will allow to achieve the afore mentioned goals by leveraging optimal academic collaborations and industrial partnerships. First, we will produce recombinant SARS-Cov-2 nucleoprotein (N) and spike glycoprotein (S) in proven expression systems and generate nanobodies directed against these 2 major antigens. Our consortium will then contribute and synergize, in connection with DARRI and S. van der Werf NRC to develop diagnostic and therapeutic applications: (i) N- and S-based serological assays will permit serological survey of exposed population and shall contribute to the sorting of suspect cases, (ii) multi-target and sensitive nanobodies-based (immunocapture) antigen detection assays shall contribute to fast and efficient sorting of suspect cases, (iii) neutralizing anti-S nanobodies will provide direct options for clinical therapeutic development and ( iv) anti-N intrabodies will be evaluated for their capacity to inhibit the replication of SARS-CoV-2 genome capitalizing on the Carnot MS IBOVIR program which aims to develop intracellularly active nanobodies (intrabodies) as an innovative antiviral approach. Efforts will also be devoted in order to (v) identify potentially broadly cross-reactive nanobodies against the S proteins of most betacoronaviruses.",,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P29263,142291,MOD-VOC,"About Project MOD-COV (Modelling of the hospital Dissemination of SARS-CoV-2) In the context of SARS-CoV-2 pandemic, healthcare institutions are faced with major challenges. First the community spread is leading to a large demand in available beds and to a saturation in hospitals dedicated to COVID-19 patients, particularly in intensive care units. Second, the outbreak and its managements are causing a large-scale disorganization of the entire healthcare system. Third, healthcare settings have been shown to be hotspots of transmission of coronaviruses, notably due to the high density of contacts. The aim of project MOD-COV is to address the risk associated with SARS-CoV-2 nosocomial transmission and support its dissemination control in health care settings. To do so, we adapt already developed models by our team in order to provide, in the short term, simulation analyzes to support health care organization and the implementation of measures to control SARS-CoV-2 dissemination in both acute-care and long-term term care, for patients and healthcare workers. The models we will develop will also allow, in the medium term, to better understand the epidemic characteristics of this virus in these specific environments and to assess a posteriori the global impact of the disorganization caused by the current epidemic, thus providing useful tools and procedures that can be used directly for future outbreaks. Collaborations: - National Conservatory of Arts and Crafts - AVIESAN/REACTING working group ""modeling SARS-Cov-2 dissemination in health care settings"" Funding: ANR, Univ Paris Saclay",,-99,N/A,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | IPC in health care settings,2020 +P29264,146675,Study of immune crosstalk in COVID-19 COVIMUNE,"About Our overall goal is to understand the cellular and molecular aspects of immune response to SARS-CoV-2 viruses in terms of activation of over-reactive immunity and induction of immune protection. COVIMUNE is designed to target the priority of ""pathophysiology of the disease"" through the following objectives 1. To develop a cellular model to study human-viral interactions on the adaptive immune response 2. To dissect of how antigen-presenting cells (APCs) polarize T cell responses leading to over-reactive immunological reaction and/or protective memory T cells 3. To investigate the role of regulatory T cell (Treg) in regulating immune responses 4. To identify CD4+ T cell epitopes of SARS-CoV-2 presented by APCs and validation of these epitopes in patients recovered from COVID-19 5. To explore underlying immune mechanisms predisposing patients with diabetes and cardiovascular diseases to severe COVID-19",,2021,N/A,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity | Disease models | Disease pathogenesis,2020 +P29265,168123,Mouse models for Covid-19,"About Mice are not naturally susceptible to SARS-CoV-2 due to poor binding of the virus spike to the mouse cellular receptor ACE2. We have developed a mouse-adapted strain of SARS-CoV-2 which efficiently replicates in the lungs of standard mice. We are using genetically diverse Collaborative Cross mouse strains to produce a variety of models differing in illness severity. We have also shown that mice are susceptible to several variants of concern (VOCs) which have spread in humans over large geographic areas, raising the possibility of secondary wild rodents reservoirs",,-99,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Disease models | Pathogen genomics, mutations and adaptations",2021 +P29266,168171,(SOCSET) Studying Olfactory and Cognitive Symptoms Evolution in long-COVID Patients,"About Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2 infection of neurons in the olfactory system has been reported in both hamsters and humans. The vast majority of patients with COVID-19 recover olfactory function within a few weeks. However, a significant minority of infected individuals (1 in 5 cases), still suffer from olfactory disorders (anosmia, hyposmia and/or parosmia) several months after primary infection. These olfactory disorders are frequently associated with depressive behavior and cognitive complaints. In PET, it is even possible to correlate this cognitive dysfunction with hypometabolism of certain brain regions, including the olfactory gyrus. This project proposes to evaluate and follow the evolution, during one year, of the olfactory capacities of patients with persistent smell disorder since one year (+/- 4 months) following COVID-19. We propose to study the link between viral persistence in the olfactory sensory organ, chronic inflammation, and central damage to the olfactory system. The follow-up of the evolution of olfactory and neurocognitive capacities, in an integrative way by means of molecular, physiological and behavioral approaches, will inform us on the specificities of the ""COVID-long"" and on the level of peripheral and/or central damage of the olfactory system. Within this framework, thirty participants will be recruited and followed in the ENT department of the Lariboisière Hospital during two one-day visits spaced out over 12 months. During these two visits, the participants will perform complete evaluation of their olfactory abilities: A self-assessment questionnaire A ""Sniffing stick test"" (Threshold, Discrimination and Olfactory Identification test) A recording of their brain activity in response to odors (PEO) A Brushing of their olfactory slits for analysis of their olfactory mucosa. A complete neurocognitive assessment: Evaluation questionnaires A blood sample for the search of plasma markers of neurological damage (12mL or 3 tubes) If you wish toto participate, you may contact the ENT secretary of Hôpital Lariboisière (APHP) by phone at 01.49.95.80.57 or by email at: nadine.barenton@aphp.fr",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2022 +P29268,143456,CORONAFISH,"About Diagnosing SARS-CoV-2 infections early, quickly, and reliably is critical to isolate patients and slow down transmission. Current RT-PCR based diagnostic tests are insufficiently accessible, time consuming and have suboptimal sensitivity. We propose to develop alternative or complementary tests based on detection of viral genomes by RNA-fluorescence in situ hybridization (RNA-FISH).",,-99,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29269,176891,ISIDORe - Integrated Services for Infectious Diseases Outbreak Research,"About Representation of MIRRI in ISIDORe The Biological Resource Center (CRBIP) represents the MIRRI infrastructure in ISIDORe. Our activities are focused on service provision (TA), but also in joint research activities. The ISIDORe project intends to capitalize on the experience and successes of these RI, and assemble an ambitious integrated, coordinated, interdisciplinary and operational scientific research instrument to provide trans-national and virtual access to its capacities to selected user scientists. ISIDORe aims at structuring and coordinating its effort and service offer according to an R&D pathway meant to support the response to an epidemic crisis and/or increase our preparedness to epidemic-prone pathogens. Overall Objectives 1) Contributing to fighting the rise of SARS-CoV2 variants through a global, integrated and challenge-driven approach by providing fast access to cutting-edge resources and services to scientific user communities for supporting the evidence -based development or adaptation of countermeasures in times of emergency, and 2) Contributing to Europe's readiness to any epidemic-prone pathogen through a global integrated preparedness-driven approach by providing access to cutting-edge resources and services to scientific user communities for supporting their projects in the field of infectious diseases in peaceful times as well as during epidemics.",,-99,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Infection prevention and control,,2022 +P29270,180960,Pro-actively addressing the challenges for an effective uptake of COVID-19 vaccination in Belgium: a transdisciplinary approach (Transvaxx project),"About The Transvaxx project aims to co-create intervention strategies with community and public health stakeholders that proactively mitigate vaccine hesitancy and maximize uptake of COVID-19 vaccination in Belgium. Mixed methods will be used, combining (i) public health stakeholders analysis (including semi-structured interviews with them) with (ii) Online social listening of vaccine narratives (iii) on-site ethnographic research and (iv) the co-development of Living-Labs where an intervention strategy to mitigate vaccine hesitancy will be co-developed together with stakeholders.",,2022,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy,2020 +P29271,162490,EpiGenCOV Consortium (Genetic Epidemiology of COVID19),"Goals The objective of the EpiGenCOV consortium is to assemble a large collection of French cohorts for the implementation of genome-wide association studies of COVID19 phenotypes. The data from this collection will allow us to better understand the roles of host genetic factors involved in the biological mechanisms linked to the susceptibility and severity of COVID19, but also the numerous symptoms associated with the infection as well as the ""covid long "".",,-99,N/A,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P29272,180962,Rapid European COVID-19 Emergency Response research (RECOVER project),"About RECOVER is one of the 18 projects that the European Union has founded in response to the COVID-19 pandemic. It aims to obtain crucial unknown information about the disease through clinical Research to help the EU fight the virus and save patients' lives. Using insights from online social listening of Covid-19 discussions, the Unit of Anthropology and Ecology of emerging diseases developed a survey to measure public confidence towards clinical trials, scientists, political authorities and confidence towards pharmaceutical products including Covid-19 vaccines. The survey was conducted in 7 European countries, its results inform public health communication and policy at European level.",,2022,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication | Policy research and interventions,2020 +P29273,148815,Red Cross health workers and the continuity of care in the COVID-19 pandemic: A mixed methods operational approach,"About Voluntary organizations provide essential support to vulnerable populations and front-line health responders to the COVID-19 pandemic. The French Red Cross (FRC) is prominent among organizations offering health and support services in the current crisis. Understood primarily of lay volunteers and some trained health workers, FRC volunteers in the Paris (France) region have faced challenges in adapting to pandemic conditions, working with sick and vulnerable populations, managing limited resources, and coping with high demand for their services. Existing studies focus on individual, social and organizational determinants of motivation, but expect less to contextual ones. Public health uncertainty about the COVID-19 pandemic is an important feature of this pandemic. Whether and how uncertainty interacts with volunteer understandings and experiences of their work and organizational relationships to contribute to Red Cross worker motivation is the focus of this investigation. This mixed-study investigates volunteer and worker motivation using anthropological methods and social network analysis.",,-99,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Volunteers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health workforce,2020 +P29274,177040,Role of inflammatory mediators as predicting factors of COVID-19 pulmonary disease,"About Covid-19 disease is characterized by dysregulated immune response leading to enhanced levels of circulating and lung inflammatory mediators. The latter include cytokines and lipid mediators (LMs) which results from increased phospholipid metabolism. The role of cytokines has been extensively examined but the implication of LMs has received little attention. Alteration of phospholipid metabolism is also associated with a number of pathophysiological processes including hydrolysis of pulmonary surfactant phospholipids and cell death or apoptosis. In the present work we examined in airways aspirates of patients with Covid-19 after their admission to ICU, the changes in the levels of LMs and their possible role in the severity of pulmonary disease of these patients.",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Disease pathogenesis,2022 +P29275,199751,Vulnerability Assessment for the Covid-19 Response in France,"About As part of the Sonar-Global COVID-19 research and response action, the Anthropology and Ecology of Disease Emergence unit (coordinator of the EC-funded Sonar-Global project) conducted a Vulnerability Assessment (VA), a research-action ethnographic methodology that identifies newly emerging categories of marginalized or excluded social groups as well as complex factors contributing to vulnerabilities and resilience among social groups as a consequence of the COVID-19 pandemic. The VA was carried out simultaneously in five European countries (France, Germany, Italy, Slovenia and Malta).",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Minority communities unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P29277,180918,Cultivating Online Safe Spaces: Addressing unspoken hesitancy to build vaccine confidence in healthcare workers in Belgium (OSS project),"About Healthcare workers (HCW) are both priority groups for vaccinations and among the most influential in layperson's vaccine decisions. Yet considerable vaccine hesitancy has been reported among HCW internationally, including in Belgium. During previous research which investigated the challenges to an effective acceptance of COVID-19 vaccination in Belgium (Transvaxx project 2020-21), we found that hesitant healthcare workers often do not voice their concerns to peers due to institutional and societal pressures to vaccinate, a phenomenon that we conceptualize as unspoken vaccine hesitancy. Healthcare workers experiencing unspoken vaccine hesitancy may have difficulties in overcoming their concerns and therefore in building vaccine confidence for themselves as well as for their patients. We propose to characterize and address healthcare workers' unspoken vaccine hesitancy in the Flemish-speaking Flanders region and the primarily French, Flemish and English-speaking Brussels region in Belgium. We conducted a hybrid social listening by bringing together online and offline vaccine concerns. Alongside participating HCW, we co-created an online safe space where vaccine concerns of healthcare workers could be discussed between peers and with the assistance of a multidisciplinary team of researchers. The intervention was documented through implementation research methods and its impact evaluated using mixed methods. Moving away from misinformation control and correction, our listening and dialogue driven method could be scaled and reapplied to other settings. It proposes to use social media as an innovative tool to build vaccine confidence and more broadly, dialogue and societal resilience.",,2022,N/A,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Communication | Vaccine/Therapeutic/ treatment hesitancy,2021 +P29278,209449,Social Sciences for Community engagement in Humanitarian Action (SS4CE in HA),"About The project's objective was to integrate and strengthen social sciences for community engagement in humanitarian settings (i.e., conflicts, natural hazards, infectious threats) drawing on some important lessons learned globally during Covid-19 and previous epidemics (e.g. Ebola) on the importance of social -science informed approaches in crisis contexts. The Sonar-Global network (coordinated by the AEE unit) was the implementing partner to this project. The consultation process led to the delivery of ""global goods"", that is co-decided global tools (i.e., competency framework, training curriculum, a framework of standards on Data Ethics in SS4CE in humanitarian action) available to the community of humanitarian workers to perform robust and effective social-science-informed community engagement. The project was coordinated by UNICEF Social and Behavior Change Bureau (NY). Collaborating partners were the University of Makerere (Uganda), Fiocruz (Brazil) and AIGHD (Netherlands).",,2022,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae,,,,,,,,,COVID-19 | Ebola virus disease,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Community engagement,2021 +P29279,143621,AFRIPOX - A One Health approach of monkeypox in Central African Republic,"About Monkeypox is an emerging Orthopoxvirus responsible for monkeypox disease, clinically similar to smallpox with a lethality of around 1 to 10%. This disease is a zoonosis initially transmitted from an animal reservoir and then spread by human-to-human and nosocomial transmission. Monkeypox has been designated by the 2018 WHO Research and Development Blueprint as an emerging disease requiring accelerated research and development of public health actions. However, little is known about this virus, its animal reservoir, the risk factors for human involvement, and the ecological and social factors that contribute to its emergence. There is no specific treatment or vaccine against monkeypox. However, the immunity given by smallpox vaccination would provide cross-immunity against monkeypox virus infection. Our project will piggyback on the national monkeypox surveillance process and will allow a holistic approach to this disease in CAR through multiple complementary approaches. This project will characterize animal reservoirs of monkeypox viruses and their ecological habitats, and will shed light on the interactions between humans and these reservoirs to identify practices that can prevent zoonotic viral transmission. Through the study of past and ongoing epidemics, we will document the epidemic potential of the disease and the risk factors associated with human-to-human transmission, with the aim of improving control measures during epidemics. At the same time, the project will characterize the ecological zones favorable to the occurrence of monkeypox epidemics in Central Africa and the recent changes characterizing these zones. Finally, the project will contribute to the reinforcement of local capacities (laboratory diagnosis, field and sequencing capacities, and infection prevention and control (IPC) capacities) in a region that experiences frequent viral emergences. The interest of this project lies in a preventive management of these potential emergences in a generic way by understanding their epidemiology and the factors involved in their emergence, and the importance of strengthening the health and surveillance systems of the countries concerned. New article 2022: https://theconversation.com/monkeypox-this-circulation-of-the-disease-is-completely-new-183517?utm_source=twitter&utm_medium=bylinetwitterbutton Other articles: https://www.linkedin.com/posts/institut-pasteur-bangui_monkeypox-centrafrique-activity-6905146708620050432-0YOX https://pasteur-bangui.org/14-january-2020-afripox-le-projet-des-instituts-pasteur-pour-contrer-le-monkeypox-en-republique-centrafricaine/https://pasteur-bangui. org/14-january-2020-afripox-the-pasteur-instituts-project-to-counter-monkeypox-in-the-central-african-republic/ https://pasteur-bangui.org/10-october-2018-monkeypox-en-republique-centrafricaine-lheure-est-a-la-prevention/",,2023,N/A,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Investigation of zoonotic transmission & reservoirs | Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics,2020 +P29280,204059,INTRANZIGEANT: Integrated study of Zika virus transmission to identify genetic mechanisms and new antiviral targets,"About Vector-borne pathogens like dengue or Zika viruses are transmitted to a human via the bite of a mosquito infected by a previous bite on an infected human. This transmission cycle is responsible for the rapid spread of emerging diseases, as exemplified by the Zika epidemic in Latin America in 2015-2016. The epidemic spread depends on the efficacy of human-to-mosquito-to-human transmission, which is influenced by the combination of host, mosquito and viral factors. This project aims to elucidate the mechanisms underlying Zika virus transmission through an integrated approach that jointly considers the genetic variation of the host, the virus and the mosquito vector, using cutting-edge technologies and biosafety facilities. The goal is to better understand the mechanisms of transmission to identify potential targets for strategies aimed at controlling the spread of vector-borne infections.",,2026,N/A,,Disease Vectors | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Immunity",2022 +P29281,148811,Anthropological Study for the Programmatic Response to Ebola Virus Disease (EVD) in the Central African Republic,"About Funded by UNICEF Central African Republic, this investigation consists of a descriptive and comparative anthropological research on social, political, economic and health relations, formal and informal structures and practices in areas at risk of Ebola outbreak. It aims to situate local definitions of vulnerability in their broader socio-political and cultural context, with particular attention to social relations, cultural, economic and environmental practices, health structures and resources, and local practices and representations of health, misfortune and disease. This analysis will form the basis for recommendations to UNICEF for the prevention of a large-scale Ebola epidemic, the strengthening of preparedness for a possible outbreak, and the control of transmission and assistance (medical and psychosocial) of sick people in the event of an Ebola epidemic. *** Funded by UNICEF Central African Republic, this investigation consists of descriptive and comparative anthropological research on social, political, economic and health relations, formal and informal structures and practices in areas at risk of an Ebola epidemic. It aims to situate local definitions of vulnerability in their broader socio-political and cultural context, paying particular attention to social relations, cultural, economic and environmental practices, health structures and resources, as well as local practices and representations of health, misfortune and illness. This analysis will form the basis of recommendations to UNICEF for the prevention of a large-scale Ebola epidemic, the strengthening of preparedness for a possible epidemic, and the control of transmission and care (medical and psychosocial) of sick people in the event of an Ebola epidemic.",,-99,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Approaches to public health interventions,2020 +P29282,146539,ZIKA,"About Zika virus multiplication and cytopathic effects The Zika virus (ZIKV) epidemics in South East Asia, French Polynesia, the Caribbean islands and the Americas, and its association with neurological disorders including Guillain-Barré syndrome and microcephaly and other defects in newborns have triggered a global public health response. ZIKV infection mainly occurs after a bite by infected Aedes mosquitoes, through maternal-fetal transmission, and less frequently by sexual transmission. In 2017, evidence of vector-borne ZIKV transmission have been reported in about 85 countries or territories. The innate immune response controls viral spread and disease development in most of infected individuals, through mechanisms that are not clearly understood. We are studying the cytopathic effect of the virus, that is to say the morphological changes of the cell, to understand what happens once the virus replicates. We recently observed that the infected cell reacts by forming massive intracellular vacuoles which leads to the death of the cell. This phenomenon of cellular destruction is mainly visible in the absence of the protein IFITM3. These observations are made in the cells naturally targeted by the viruses, including epithelial cells, fibroblasts of the skin and brain astrocytes. These observations are made in the cells naturally targeted by the viruses, including epithelial cells, fibroblasts of the skin and brain astrocytes. Our aim is to understand how Zika virus replicates despite this massive cytopathic effect, and to further describe the protective innate response of the host. We are using video microscopy electron microscopy and other techniques to address these questions. Zika Virus particles accumulating in infected cells, visualized by electron microscopy. Scientific image by François Rabelais University, Tours and Institut Pasteur, Paris, France Cell infected with Zika virus (cytopathic effect), with massive vacuoles (holes). In red: viral proteins. In green: cell. In blue: nucleus. Immunofluorescence microscopy (Institut Pasteur). ZIKV modifies the morphology of the cells and makes them implode. Example of HeLa cells. ZIKV modifies the morphology of the cells and makes them implode. Example of primary human skin fibroblasts.",,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P29283,217648,Development of a new vaccine against Plague,"About Although an effort towards vaccination is ongoing, no efficient and safe vaccine against plague is currently available. During the last decade, we developed a new vaccine against plague. The project was funded by a series of grants (Ministry of Research, Pasteur Institute, NRBC program via CEA, National Research Agency-ANR, DGA). Our live attenuated oral vaccine is based on Y. pseudotuberculosis, the ancestor of Y. pestis with which it is genetically almost identical, although much less virulent and genetically more stable. We first demonstrated that a Y. pseudotuberculosis could be used by means of a naturally avirulent strain form our collection, but then constructed a genetically defined strain by modifying a Y. pseudotuberculosis which genome was fully sequenced. This new plague vaccine candidate, named VTnF1, was constructed by deleting the genes for three essential virulence factors from the strain IP32953, the first whose genome was known. In addition, the operon encoding the highly immunogenic Y. pestis F1 pseudocapsule antigen was inserted in the chromosome to induce the production of the highly protective F1 antigen, an abundant surface signature of the plague bacillus that elicits a protective antibody response. The absence of pathogenicity of this new vaccine and its ability to induce a good humoral and cellular response against Y. pestis have been demonstrated. More recently, a strain without antibiotic resistance cassettes has been reconstructed. By the oral route, natural to Y. pseudotuberculosis, VTnF1 protects mice 100% against lethal pneumonic plague caused by 3000 times the median lethal dose (MLD) of Y. pestis. VTnF1 also protects 100% against bubonic plague, up to 10000 DML. The worst bioterror threat using plague would be an attack with infectious aerosols, to cause highly contagious and rapidly fatal pneumonic plague. An F1-negative Y. pestis, as a potential bacteriological threat, would then be undetectable by common tests and resistant to F1 immunity. In mice, our VTnF1 vaccine confers protection against this type of infection. This long-term project benefits from the support of the ""Direction des Vaccines"" of the Institut Pasteur.",,-99,N/A,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Yersiniaceae,,,,,,,,,Plague,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",Pre-clinical studies,2024 +P29289,138030,Modulation of HCV replication by novel effectors of the interferon response,"About The interferon (IFN) response protects cells from invading viral pathogens by transcriptionally inducing the expression of interferon-stimulated genes (ISGs). Only a handful of these ISGs have been well characterized, mainly by artificial gain-of-function screening approaches. We developed an original library of 1156 siRNAs targeting around 386 individual curated human ISGs (46% new) for loss-of-function screening. We have already identified poorly-characterized ISGs that modulate the replication of Zika virus, an emerging RNA virus that belongs to the flaviviridae family. We propose to use the same approach to identify ISGs that modulate infection of Hepatitis C virus (HCV), which also belongs to the flaviviridae family. Our long-term goal is to perform an in-depth characterization of the mode of action of a set of IFN effectors that exhibit either HCV-specific or pan-flaviviridae modulatory activities. Our work will increase our fundamental knowledge of antiviral response against members of the flaviviridae family. Furthermore, taking advantage of some of these naturally occurring pan-viral inhibitors may be an effective strategy in the development of novel drugs that activate, amplify or mimic their action.",,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2020 +P29290,155690,Effectors of the innate immune response against tick-borne encephalitis virus,"About Tick-borne encephalitis virus (TBEV) is a growing health concern in Europe and Asia. It causes severe disease that can lead to permanent neurological complications or death. Recently, the incidence of TBEV infections in endemic regions increased despite a functional vaccine being available. This makes further investigation of the pathogenesis of the virus essential. Exploiting host defense mechanisms against TBEV as therapeutic strategies thereby appears as a promising approach. The first line of defense against pathogenic intruders in eukaryotes is the innate immune system. Its importance, especially in the form of IFN-signaling cascades, was previously revealed also in the context of TBEV infection. IFN signaling results in the expression of a plethora of IFN-stimulated genes (ISGs), many of which are not well characterized. In this project I propose an extensive siRNA library-based screening approach aiming to assess the importance of distinct ISGs for the antiviral response against TBEV. This will be followed by an in-depth characterization of the mode of action for the ISG candidate exhibiting the most potent antiviral qualities. The identified ISG will, in the following, be investigated in the context of infections with other pathogenic members of the flavivirus family currently presenting big challenges to global health, such as Dengue and Zika viruses.",,-99,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Other,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P29291,161241,Discontinuities and Vector-Borne Diseases in Urban Areas,"About Vector-borne diseases (dengue, Zika, chikungunya) are an important public health issue. Understanding their transmission dynamics remains a major challenge at the sub-urban level. Indeed, environmental heterogeneities, variations in vector densities and daily mobility hinder the definition of epidemic risk indicators at this scale. MO3 therefore aims to (i) develop a simulation model to study the sensitivity of epidemic dynamics to targeted scenarios of vector control and (ii) evaluate in a large metropolis where dengue is endemic, Bangkok (Thailand), the effectiveness of these strategies. To achieve these objectives, the MO3 project will rely on SEIR and agent-based models, with high spatial and temporal resolution, to finely describe the urbanized space and the variety of dynamics that unfold there. Vector dynamics will be influenced by the spatial and temporal heterogeneity of their ecological niche, those of humans by their daily mobility, partly linked to their place of residence, their socio-economic profile and their age. The calibration of the model will be based on various data: satellite images, census, social networks, transport ridership, vector and epidemiological retrospective data already accumulated during the EU DENFREE consortium. We also plan prospective field surveys. Sites will be selected according to the suitability of the ecological niche for the vector and a value gradient of centrality of the places. Weekly surveys over a 2-year period will be used to analyze the evolution of adult mosquito stocks with respect to these two indicators, and epidemiological surveys of at-risk populations will be used to assess exposure levels, according to these two indicators. All of this data will then be used to calibrate and validate the simulation model. These methods will also evaluate and compare vector control strategies against the epidemiological dynamics simulated by the model, in search of the most effective strategy or strategies. In collaboration with Chulalongkorn University, Institute for Urban Disease Control and Prevention and the Siam Cement Group, we will then implement novel vector techniques guided by the models. MO3's ambition is therefore to develop a generic method that allows for vector-based control in priority areas, thus enabling local actors to optimally allocate their available but limited resources.",,-99,N/A,,Other,Not applicable,Not Applicable,Urban Population/Setting,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Other,Institut Pasteur International Network (IPIN),France,Europe,Unspecified,Unspecified,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector biology | Vector control strategies | Disease transmission dynamics | Disease surveillance & mapping,2020 +P29292,1.015E+13,Immunogenicity of fractional subcutaneous booster vaccination against mpox: a non-inferiority study,"Although mpox incidence has significantly declined since the outbreak in 2022, recurrence of monkey pox virus (MPXV) circulation remains possible. With a continuous risk of reintroduction of MPXV into a highly susceptible population with absent or waning immunity, there is no room for complacency. The relative contribution of vaccination to the interruption of the outbreak is not fully understood. Initial studies showed that the MVA-BN vaccine had low immunogenicity, but that antibody levels are significantly boosted if a third shot is administered one year after the primary vaccination regimen. Aim The aim of this study is to prove that a boost can also be given with a 1/5 fractional dose, and that this is not inferior to the standard dose with regards to the induction of immunogenicity. (Expected) results If fractional dosing proves non-inferior to the standard dose, significant dose-sparing can be achieved with less side effects, which could prove essential in the interruption of future mpox outbreaks.",,2026,Leids Universitair Medisch Centrum,,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines | Immunisation strategies to optimise use of available vaccines",Netherlands,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2024 +P29293,1.015E+13,Longevity of orthopoxvirus-specific immune responses induced by infection or vaccinationinfectie,"In 2022, an unprecedented mpox outbreak occurred in many countries with no prior history of mpox, resulting in the WHO declaring a public health emergency of international concern. In an effort to interrupt the outbreak and reduce future risk, vaccination was offered to groups at risk of contracting mpox, mainly men who have sex with men (MSM). Although the outbreak seems to be contained for now, new cases continue to emerge, including in MSM with pre-existing immunity induced by prior vaccination or infection. This indicates that virus-specific immunity is not long-lived. Approach/working method This project aims to study and compare the magnitude and longevity of immunity induced by either vaccination or infection by performing long-term follow-up and immunological analyses. (Expected) results The results will inform MSM on their current immune status and policy makers with regards to the necessity of potential booster vaccinations. Additionally, they allow for optimal preparedness in case of mpox re-emergence.",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Other,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines | Immunisation strategies to optimise use of available vaccines",Netherlands,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2024 +P29294,1.015E+13,"U-swab: Acceptability, utility, feasibility of self-swabs in primary care respiratory surveillance","A primary care respiratory surveillance network is indispensable for monitoring public health. The Nivel Primary Care Database Sentinel Practices is a long-standing surveillance network for respiratory infections in primary care practices in the Netherlands. General practitioners take a deep nasal and throat swab from patients presenting with flu-like illness. This sample collection is becoming more difficult due to increasing strain on GPs, an increase in remote consultations, changed care seeking behaviour and an increased resistance to especially the deep nasal swab. Based on the experience with self-swabbing during the COVID-19 pandemic, we expect that self-collection of nasal/throat samples can mitigate these obstacles. Approach/working method In this controlled study we evaluate the acceptability, utility and feasibility of self-swabbing instead of physician-swabbing. (Expected) results The results of this study strengthen primary care surveillance which is important for targeted control, prevention and communication.",,2026,Nivel,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Impact/ effectiveness of control measures,2024 +P29295,1.015E+13,Bacterial and host determinants to explain and control group A streptococcal infections (BEATGAS),"Group A Streptococcus (GAS) is a bacterium that asymptomatically resides in the oropharynx of ~10% of the population. In rare cases, GAS invades deeper tissues or even the bloodstream, causing life-threatening so-called invasive GAS (iGAS) infections. After lifting the COVID-19 control measures in the Netherlands in March 2022, a resurgence of iGAS infections occurred among children and adults. Aim This project aims to uncover the reasons for this ongoing outbreak by: investigating and comparing the genomes and biological traits of GAS isolates before and after the COVID period to gauge changes in its' disease-causing potential, and by; measuring the levels of anti-GAS antibodies before, during, and after the period of COVID restriction measures in specific age groups. (Expected) results Finally, we aim to provide broad insight into current risk factors for primary iGAS and the effect of the recently-expanded antibiotic prophylaxis guideline to prevent secondary iGAS infections.",,2028,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29296,1.108E+13,Post-COVID Network Netherlands,"The Post-COVID Network Netherlands is a national partnership in which patients, scientists, healthcare professionals and social partners work together to coordinate scientific research and patient care for people with post-COVID with each other. This coordination systematically and efficiently builds up knowledge that is needed to better understand post-COVID, make a better diagnosis and develop better treatment options. The network actively promotes the use of all relevant knowledge to continuously improve care for people with post-COVID.",,2027,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Clinical characterisation and management,Post acute and long term health consequences,2024 +P29297,1.071E+13,The role of telemedicine and remote care in increasing pandemic resilience,"During the COVID-19 pandemic, patients have stayed in touch with their healthcare providers in a variety of digital ways, keeping them safely connected. However, this form of 'remote care' was not always preferred by all patients. The question now is how the options for 'telemedicine' can best be used in the future to help patients as best as possible.",,2024,Erasmus Medisch Centrum,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2024 +P29298,1.071E+13,Mental well-being and resilience during a pandemic: co-creating with students,"The COVID-19 pandemic has caused many problems. Measures to stop the virus were necessary, but also increased loneliness, depression and anxiety among young adult students. In addition, the social and social development of this group is limited, with visible consequences. For pandemic preparedness, it is important to learn from COVID-19.",,2024,Avans Hogeschool,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Indirect health impacts,2024 +P29299,1.071E+13,INTEGREAT Implementation of opportunistic (rapid) testing among immigrants for pandemic preparedness,"During the COVID-19 pandemic, it became clear that immigrants in the Netherlands were tested and vaccinated less often. This project focuses on integrating rapid tests for hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) into the existing screening process for tuberculosis (TB) in immigrants. This will improve healthcare for immigrants and prevent the spread of infectious diseases. This approach serves as an example of a feasibility pilot to make testing more accessible to immigrant populations by opportunistically offering rapid testing during a pandemic.",,2024,GGD Zuid Limburg,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control",Diagnostics,2024 +P29300,1.071E+13,Misinformation and pandemic preparedness: an intervention study,"Citizens play a crucial role in pandemic resilience. For example, they must have enough knowledge and action perspectives to demonstrate the correct behavior in the event of a pandemic that limits the spread. Research into the COVID-19 pandemic shows that this is not self-evident.",,2024,Wageningen University & Research,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience",Communication,2024 +P29301,1.071E+13,Mobility in the field of vaccinations in the South Limburg region,"During the COVID pandemic, citizens in South Limburg appeared to get COVID-19 vaccinations in Aachen. Vaccinating across the border can distort the vaccination rate in border regions. For pandemic preparedness, it is important to know which part of the population is vaccinated abroad.",,2024,GGD Zuid Limburg,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Health Systems Research",Vaccine/Therapeutic/ treatment hesitancy | Health information systems,2024 +P29302,1.071E+13,Explore the impact of environmental pollutants to the pathogenesis of emerging viruses,"Human exposure to environmental pollutants is increasingly linked to increased susceptibility to viral diseases. This link was highlighted during the COVID-19 pandemic, as there were suspicions that environmental pollution would promote the spread of pandemic viruses. Nevertheless, the precise impact of this association between pollutants and emerging viruses is largely unclear.",,2024,Erasmus Medisch Centrum,,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Unspecified,,,,,,,,,COVID-19 | Disease X,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease transmission dynamics,2024 +P29303,1.071E+13,A pandemic preparedness platform for patients with chronic inflammatory conditions,"During the COVID-19 pandemic, the Amsterdam Rheumatology Center conducted a large prospective cohort study to answer questions related to COVID-19 in patients with chronic inflammatory conditions. Using digital questionnaires and finger-prick blood samples, they were able to respond quickly to changes in the pandemic. This has helped answer several questions about COVID-19 and adjust vaccination and treatment guidelines for these patients. The result was the development of a platform useful for epidemiological research and information provision for vulnerable groups during a pandemic.",,2024,Reade,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease susceptibility,2024 +P29304,1.04304E+13,Mental health and well-being of children and young people: lessons from the COVID-19 pandemic,"From April 2020, we will be following 4 large groups of children and young people to investigate the effect of the COVID-19 pandemic on mental health. Every six months (7 times) we sent the same questionnaires to children and their parents. Our results show that mental health problems such as anxiety and depression increased during the pandemic and have still not returned to pre-pandemic levels in 2023. So far we have mainly looked at average scores on the questionnaires. To gain more insight into vulnerable groups, we now want to look at the individual trajectories of children. This is possible because there are children who have participated in our research several times. We will also look at the reasons why children developed more mental problems. We do this with the answers that children have given to open questions. Our goal is that all children in the Netherlands grow up mentally healthy, even in times of a pandemic!",,2024,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29305,1.04304E+13,Patterns of COVID19-related information provision in relation to care avoidance and mortality,"During the pandemic, information about COVID-19 has been communicated in various ways. Through traditional channels such as TV or newspaper, but also often through social media. The way in which people received information may have influenced their behavior in relation to their health. In this study, we determine the relationship between the way people obtained information about COVID-19 in relation to their help-seeking behavior and the resulting risk of mortality in the general population. To this end, we bring together harmonized data from two large, long-term population studies, the Generation R Research (0-40 years) and the Erasmus Rotterdam Health Research (40-107 years). Together these studies cover the life course. For example, we carefully investigate how, for example, the government can inform people as best as possible in the future, focusing on the information needs of different ages.",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience",Communication,2024 +P29306,1.04304E+13,The unequal distribution of the consequences of the COVID-19 pandemic,"The unequal distribution of the consequences of the COVID-19 pandemic The corona pandemic, both the virus itself and the many restrictive government measures to prevent the spread of the virus, had major consequences for Dutch society: not only overcrowded hospitals and many deaths, but also social disruption due to the closure of schools, shops and companies and the call to work from home and avoid social contacts. All this had major consequences for Dutch people: people were afraid of losing work and income, became lonely and suffered from anxiety and depressive feelings. We investigate whether these negative consequences of the pandemic are unevenly distributed in society. In particular, we examine whether traditionally vulnerable groups (such as the less educated, the elderly and people with poor health) and new vulnerable groups (such as the self-employed) have been hit harder than others. We use data from five large-scale surveys conducted during the pandemic (between April 2020 and September 2021). In total, almost 100 thousand people answered our questions. Central themes in our research are: the dramatic loss of trust in government, which started during the pandemic and is still ongoing, the mental consequences of the pandemic, whether there was an accumulation of negative consequences of the pandemic among certain social groups , and so forth.",,2024,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2024 +P29307,1.04304E+13,The long-term effects of the COVID-19 pandemic on people with low literacy and/or people with a disability,"The corona pandemic has had major consequences for vulnerable target groups, such as people with mild intellectual disabilities (LVB) and/or low literacy. Research specially adapted to the target group shows that they have been hit hard both physically and mentally, for example, they experienced loneliness and reduced mental health more often than the general population. However, the long-term effects of the pandemic for these target groups are unknown. This project therefore conducts follow-up research to gather knowledge about the physical, mental and social challenges they still experience as a result of the pandemic and how they look back on the measures. Through an accessible health monitor - an inclusive online questionnaire with support - participants can share their experiences and needs. The research provides valuable insights to develop targeted support programs to address and mitigate the consequences of the pandemic.",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Indirect health impacts | Social impacts,2024 +P29308,1.04304E+13,"Impact of COVID-19 measures on mental health, resilience and job satisfaction of healthcare workers","The COVID-19 pandemic has had a huge impact on mental health. Healthcare workers were at the front line in the care of terminally ill patients and were the subject of social debate (partly due to the shortage of ICU nurses). The government measures had a major impact on their work. That is why it is important to investigate the effects of these measures on the mental well-being, resilience and job satisfaction of this group. Within our project, we previously investigated the mental health of approximately 400 hospital employees during and after the COVID-19 pandemic, using questionnaires. In this follow-up study, we will further explore the views of healthcare workers with in-depth interviews. What protected against stress and which measures caused high work pressure? This will provide us with more insight into the effects on mental health and allow government policy to be better aligned with the support of healthcare workers.",,2024,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2024 +P29309,1.04304E+13,Lifestyle of young people and parents during the pandemic: The role of measures and relationship quality,"It is important for people's health that they smoke less, drink less alcohol and are less overweight. The measures during the COVID-19 pandemic (such as the closure of schools, mandatory working from home, and the closure of sports clubs) may have influenced people's health behavior. With this study we therefore examine whether health behavior (namely smoking, drinking alcohol, healthy eating, and exercising) and Body Mass Index (BMI; a measure that shows whether weight is healthy in relation to height) in young people and their parents has changed due to the COVID-19 measures. We will also investigate whether parents and their children show more or less the same health behavior during different phases of the pandemic (such as during lockdowns and partial reopenings). We will also look at whether a good relationship between parents and their children might influence all these possible changes, because parents and their children were together more often during lockdowns. We use data from the ""G(V)OED for each other"" study for this purpose. This research will provide us with more knowledge about how we can improve the healthy behavior of young people and their parents.",,2024,Radboud Universiteit Nijmegen,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29310,1.04304E+13,COVID-UNCOVERED: A visual ethnography about the impact of measures on socially vulnerable groups,"The corona period has had a major impact on the elderly, people with mild intellectual disabilities (LVB) and home and homeless people. Now that the pandemic is over, we, researchers at the University of Amsterdam, want to know how they are doing. To find out, we interview a number of people from these three groups. Together we talk about the corona period, the measures, and how things are going now. Sometimes we also talk to people who are important to them; such as a family member, friend, supervisor or caregiver. We film and take photos during these interviews. We use these images to make a short film per group. Together with the organizations MEE Zaanstreek-Waterland and Ben Sajet, we will then show the films to the participants and then discuss the corona period and the lessons learned. We also share the films online and use them for an online course for supervisors on our website www.coronatijden.nl .",,2024,Universiteit van Amsterdam,,Human Populations,Unspecified,Older adults (65 and older) | Unspecified,Unspecified,Other,Caregivers | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29311,1.04304E+13,CONTROL-2: Evaluation of CONTact Reducing Government Measures,"During the COVID-19 pandemic, many measures have been introduced to reduce the number of people's contacts and prevent the spread of SARS-CoV-2. However, the effectiveness of these measures has not been sufficiently evaluated. We do know that they have had a negative impact on psychosocial health and the economy. That is why we want to investigate which measures have been most effective in reducing the number of contacts, and are therefore most suitable for use in the next outbreak. For the CONTROL project, we (9 GGD regions and the RIVM) collaborated and used SARS-CoV-2 test data and source and contact investigation (BCO) data to investigate the effectiveness of the BCO. We will now use the same data to investigate to what extent the number of contacts reported during contact research by people who tested positive was influenced by the nature and severity of measures introduced by the government.",,2024,GGD Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Impact/ effectiveness of control measures,2024 +P29312,1.04304E+13,Digitally visiting people with intellectual disabilities: The new normal?,"Participating in society is a major challenge for people with an intellectual disability. They experience loneliness more than average. It is therefore important to consider what the COVID-19 measures have meant for this group and their loved ones. Particularly due to restrictions on physical visits, they temporarily had to rely on digital forms of contact with loved ones and for many this was new. In this project we hope to learn to what extent digital contact has proven to be a feasible and attractive option for residents of healthcare institutions. The measures may have had the side effect that more people were able to participate digitally, thanks to testing by residents, loved ones and supervisors. We also ask whether resources and support have improved through digital contact. We use repeated questionnaires and reports from supervisors over the period 2016-2023. We use the results to make recommendations for all stakeholders and policy.",,2024,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29313,1.04304E+13,An unexpected false start on the labor market,"During the COVID-19 pandemic, the government has taken measures to limit unemployment and maintain employment. For people looking for work, these measures are probably not effective. In this study, we follow young people who enter the labor market after completing their education and are looking for a first job. They are in a vulnerable position if they are ill due to an infection or if they have completed an education in a profession that has been affected by a lockdown. Scientific research shows that people who enter the labor market during a crisis earn less and are less likely to have a permanent job. With this study, we analyze to what extent this also applies to the COVID-19 pandemic. We map out which young people have been hit hardest and what the extent of the damage is.",,2024,SEO Economisch Onderzoek,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2024 +P29314,1.04304E+13,The influence of the COVID measures on long-term cancer care and survival.,"This project will provide insight into 1) to what extent the changes in cancer care implemented during the COVID pandemic are still being applied and 2) the effects of these changes on the survival of patients with cancer. The project is the first to focus on changes in care for breast cancer patients, such as starting anti-hormonal treatment instead of surgery and radiation with shorter schedules. Secondly, the survival of patients diagnosed with cancers with a poor prognosis, for example esophageal, pancreatic, stomach, oral and pharyngeal cancer and metastases at diagnosis, is studied. Possible factors that influence care and survival (such as socio-economic status) are investigated. The insights are obtained based on data from the Dutch cancer registry (supplemented with radiotherapy data). New insights can support decision-making in future scarcity within healthcare.",,2024,Integraal Kankercentrum Nederland,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P29315,1.04304E+13,Consultation with relatives: medium-term consequences of the COVID-19 measures for relatives,"During the corona pandemic, we investigated four times how loved ones of people with an intellectual disability were doing and we asked about their well-being, that of their family member, their contacts, and care tasks. In this additional research, we ask the same relatives to answer questions about four topics in their own words as much as possible. We are curious whether loved ones (1) and their family members (2) have recovered and what consequences they experience from the corona measures. This knowledge contributes to improving crisis policy, aftercare in crises and support for loved ones. In addition, we investigate whether relatives arrange future care (3) and whether they experience changes in the provision of information and participation among healthcare providers (4) after the pandemic. This knowledge contributes to issues of scarcity and collaboration with loved ones in disability care. We disseminate and discuss the results with relatives, professionals, policy makers, healthcare providers and researchers.",,2024,Nivel,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Policies for public health, disease control & community resilience",Indirect health impacts | Approaches to public health interventions,2024 +P29316,1.04304E+13,Mobility and behavior-based ex-post evaluation of effectiveness of COVID-19 measures,"During the COVID-19 pandemic, governments have imposed contact limiting measures, such as working from home, closing restaurants and cultural institutions, closing public buildings, limiting gatherings and visits, and imposing a curfew. These contact limiting measures had an enormous impact on people's social lives, work and education. The team of researchers from different fields - social sciences, epidemic modeling and public health - will evaluate the effectiveness of contact limiting measures by looking at 2 data sources: the number of trips per week between municipalities in the Netherlands during the pandemic, and self-reported social distancing behaviour. The results are important both for our scientific understanding of epidemics and for informing policy decisions in future pandemic emergencies.",,2024,Technische Universiteit Eindhoven,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2024 +P29317,1.04304E+13,Lessons from COVID-19: Long-lasting effects of Corona on people experiencing homelessness,"In 2020, the 'Homelessness and Corona' project was started to investigate the impact of the pandemic on homeless people in the Netherlands. The aim was to map the spread of COVID-19 and the consequences of the pandemic for homeless people, healthcare professionals and policy makers. Now we want to gain more insight into the long-term consequences of the pandemic and how policy and care and shelter are prepared for future outbreaks. We will conduct additional measurements and interviews with experienced experts, shelter organizations, street doctors and municipal policy officers. We want to use the results to develop advice together with all those involved for care and shelter in preparation for a pandemic and what to do during a pandemic. Together with the stakeholder group, we will also look at how these advice can best be disseminated and implemented. In this way we contribute to better preparation and protection of homeless people during future pandemics.",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2024 +P29318,1.04304E+13,The consequences of digital access to justice for vulnerable litigants post-COVID,"This research looks at what the Judiciary has learned from the problems with court cases held via video calling during the corona pandemic. During the handling of these cases, the rights of vulnerable people were sometimes at risk. The research is important because the Judiciary wants to give legal cases via video calling a permanent place in the Dutch courts and wants to be prepared for a new pandemic. In the research we interview judges and other professional groups. We also collect good practical experiences in other countries. This way we see which problems have already been solved and how the Judiciary can best tackle the remaining problems. The research helps to improve the position of vulnerable people for legal proceedings via video calling.",,2024,Radboud Universiteit Nijmegen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2024 +P29319,1.071E+13,Development of infection prevention toolbox for primary care,"Infection prevention plays a crucial role in general practices to protect both patients and healthcare professionals. It is therefore essential that GP practices are well prepared to prevent infections, especially during the autumn and winter season when respiratory viruses such as influenza and COVID-19 are common.",,2024,GGD Zuid Limburg,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Infection prevention and control,IPC in health care settings,2024 +P29320,1.04304E+13,The effects of postponed care during the COVID-19 pandemic on medium-term healthcare use,"During the first 2 major outbreaks of COVID-19 in 2020, much planned care (not related to COVID) was stopped. This was done to reduce pressure on hospitals and prevent the virus from spreading. We don't yet know exactly what the consequences of this were. For example, it is not known whether people later received the care they needed. In this study we use information about the use of hospital care to see what the consequences are of discontinuing care after a longer period of time. We look at all people in the Netherlands in total, but also specifically at vulnerable groups. Previous research showed that some people received less care than others. We are investigating whether they caught up with this later. This research shows what happens to our healthcare system if less care is provided and which people are extra vulnerable to this. This is important because we can learn lessons from this for the next pandemic. Both for stopping planned care and for catching up on that care.",,2024,Amsterdam health & technology institute,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2023 +P29321,1.04301E+13,Quality improvement of Interdisciplinary Rehabilitation for COVID-19 started in the ICU,"Many people affected by COVID-19 and treated in an ICU are unable to resume their previous position in society. Goal Our research proposal focuses on the relationship between person-oriented interdisciplinary treatment (medical specialist rehabilitation) of ICU patients with COVID-19 and their long-term functioning in the areas of exercise tolerance, lung function, cognitive functioning, mood and daily activities/participation. Research design This research complements knowledge about COVID-19 by focusing on the early, critical phase in two work packages. Work package 1, quantitative research, inventories and analyzes the method of rehabilitation treatment during the pandemic using existing data from Dutch hospitals. Work package 2, qualitative research, evaluates the implementation of the rehabilitation treatment provided through semi-structured focus group interviews with healthcare professionals working during the pandemic. Executive parties Máxima Medical Center, Adelante Zorggroep, Rivierenland Hospital, Medisch Spectrum Twente, Elizabeth Tweesteden Hospital, Amsterdam UMC, Erasmus MC and UMC Utrecht. Context This research is one of the studies in the field of research into optimal medical specialist care for COVID-19. The aim of the studies is to answer important knowledge gaps in the field of treatment. ZonMw facilitates these studies in the COVID-19 Treatment sub-programme to contribute to promoting optimal care for COVID-19. The knowledge gaps have been identified by the Multidisciplinary COVID-19 Science Committee of the Federation of Medical Specialists (FMS). More information Main applicant, project leader and secretary: Dr. CD. Bakker (Máxima Medical Center)",,2025,Not available,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2023 +P29322,1.04303E+13,"The right care in the right place: evaluation, further development and broader implementation of The Northern Initiative Multidisciplinary Collaboration for patients with persistent complaints after COVID-19 in a participatory action research ( NIMSPAKC study","Why are we doing this project? It is important to work well together in the region in the care of people with persistent complaints after COVID-19 so that care meets the needs of patients and can be organized close to home. What results does this project deliver? With this project we hope to make the current post-COVID care in the three Northern provinces more person-oriented, broadly accessible and effective. Why is this project important for patients and their loved ones? One in eight people develop persistent complaints after a COVID-19 infection. This has a huge impact on their daily lives. It is important to be able to provide the right care in the right place in a timely manner. How are we going to implement this project? We evaluate current care in the North, apply the results in practice and thus ensure continued development of better care in the North. We do this together with all relevant stakeholders in a participatory action research.",,2026,Medisch Centrum Leeuwarden,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Clinical characterisation and management",Community engagement | Post acute and long term health consequences,2023 +P29323,1.04302E+13,"To be yourself in an online world during Covid-19. Experiencing negative events, (problematic) social media use and the impact on feelings of authenticity in Dutch young people: boys versus girls.","Being true to yourself and showing who you are, that is, being authentic, is essential for the health and well-being of young people. During the COVID-19 pandemic, social media use among young people increased. This way they could maintain social contacts and deal with negative events related to the pandemic, such as closing schools, becoming ill with the virus themselves or becoming ill or even the death of loved ones. In this study we investigate to what extent experiencing negative events related to COVID-19 led to more (problematic) use of social media and whether there is a negative impact on authenticity, especially for girls. This knowledge is relevant for young people, their parents and (preventive) youth health care professionals to better deal with the use of social media and the impact this can have on the authenticity of young people, both in times of corona and afterwards.",,2024,Tilburg University,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2023 +P29324,1.04303E+13,Supervising and evaluating regional recovery and aftercare for persistent complaints after COVID-19.,"Why are we doing this project? Good organization of care is an important condition for care that meets the needs of people with persistent complaints after COVID-19. What results does this project deliver? After the project, we understand how COVID care in the region can be personalized, affordable, widely accessible and effective. Why is this project important for patients/clients and their loved ones? One in eight people experience persistent complaints after COVID-19. Where someone lives determines what care they receive. With the lessons learned from this project, we hope to help healthcare providers and patients in the Netherlands organize healthcare as best as possible. How are we going to implement this project? We will follow various initiatives that aim to improve regional care for people with persistent complaints after COVID-19. With these initiatives we learn by sharing knowledge and experiences and merging the findings. We then share these findings with healthcare providers, policy makers and patients in the Netherlands.",,2027,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2023 +P29326,05160482310002,Outcome-oriented and patient-experienced impact of the COVID-19 pandemic on healthcare accessibility and use of rheumatological care in the Netherlands,"During the COVID-19 pandemic, there was reduced accessibility to outpatient care for rheumatoid arthritis (RA) patients due to care downscaling, but also because some patients chose to avoid the overburdened healthcare system. As a result, rheumatological care has been delivered in a different way, including the accelerated adaptation of remote care. Goal The aim of this quantitative and qualitative research is to use outcome information to substantiate the knowledge gap as to whether the (drug) treatment for RA patients was optimal during the COVID-19 pandemic by reducing the number of physical consultations. Method By using real-world data, we gain insight into the further development of appropriate care during the accelerated implementation of care substitution. This knowledge will be used to optimize the care process and as a starting point for the outcome-oriented delivery of rheumatological care from a social and patient perspective.",,2025,Maasstad Ziekenhuis,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29327,1.04303E+13,Post-COVID Knowledge Agenda - project 1,"Much is still unknown about the care of post-COVID patients. Through this knowledge agenda we want to provide insight into which knowledge questions are the most important to explore and therefore solve in research. The knowledge agenda describes the highest-priority knowledge gaps in the field of post-COVID care. Research into these knowledge gaps is important for patients to conduct, so that knowledge can be used for better diagnosis, treatment and aftercare of patients with post-COVID. This knowledge agenda is compiled together with a working group of various specialists (such as a rehabilitation doctor, pulmonologist, internist, pediatrician, clinical geriatrician, general practitioner, physiotherapist, patient organizations). A meeting will be held with all relevant parties to vote on the most important knowledge questions.",,2024,Not available,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P29328,08590092310002,Post-COVID Knowledge Agenda - project 2,"Much is still unknown about the care of post-COVID patients. Through this knowledge agenda we want to provide insight into which knowledge questions are the most important to explore and therefore solve in research. The knowledge agenda describes the highest-priority knowledge gaps in the field of post-COVID care. Research into these knowledge gaps is important for patients to conduct, so that knowledge can be used for better diagnosis, treatment and aftercare of patients with post-COVID. This knowledge agenda is compiled together with a working group of various specialists (such as a rehabilitation doctor, pulmonologist, internist, pediatrician, clinical geriatrician, general practitioner, physiotherapist, patient organizations). A meeting will be held with all relevant parties to vote on the most important knowledge questions.",,2024,Not available,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P29329,1.071E+13,NCOH Pandemic Preparedness Research Kickstarter,"The outbreak of the COVID-19 pandemic in 2020 has had enormous consequences for public health, society and the economy worldwide. One of the biggest lessons we can learn from recent years is that we need to be better prepared for future crises including outbreaks and pandemics.",,2024,Universiteit Utrecht,,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,,,2023 +P29330,1.03901E+13,Mechanical ventilation in veno-venous extracorporeal membrane oxygenation (McVEE),"ECMO is a compact heart-lung machine that can be used in the ICU for months to treat patients with lung failure, e.g. due to COVID-19, who would otherwise almost certainly die. Mortality is also high with ECMO (45%), partly due to lung damage caused by ventilation. Ventilation seems unnecessary because ECMO takes over lung function, but there is discussion. Most doctors give patients anesthesia for weeks to let the ventilator take over the ventilation so that the lungs can 'rest'. The alternative is spontaneous ventilation where the patient is awake and breathing on his or her own. 'Lung rest' is more difficult to impose, but has the advantage that the patient can be mobilized, which prevents muscle weakness (including respiratory muscles). To determine the extent to which patients breathe spontaneously, we will monitor this for a year on all 200 ECMO patients in the Netherlands. We expect survival to be higher if patients breathe spontaneously <72 hours after starting ECMO.",,2024,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2023 +P29331,1.04301E+13,SCOOP: SCreening for Malnutrition and Obesity in Patients with Covid-19 and other diseases,"More than half of the Dutch population is overweight or obese. This is associated with an increased risk and an unfavorable course of Covid-19. In addition, malnutrition and loss of muscle mass are often reported with Covid-19, but also with cancer and other diseases. Malnutrition and overweight or obesity can coexist (within one individual). It is still unclear which mechanisms contribute to the worse course of Covid-19 and other diseases in overweight and obesity, in malnutrition, and in the combination of the two. Through literature research and database research (Covid-19 and cancer, more than 150,000 participants), we want to identify which nutritional parameters are associated with an unfavorable course of the disease. In addition, we aim to use a clinical study to develop a simple screening instrument for recognizing the combination of malnutrition and overweight or obesity in clinical practice.",,2025,HAN University of Applied Sciences,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Prognostic factors for disease severity,2023 +P29332,1.071E+13,BEhavioural and social sciences and pandemic PREPAREDness: the BePrepared Consortium,"The outbreak of the COVID-19 pandemic in 2020 has had enormous consequences for public health, society and the economy worldwide. One of the biggest lessons we can learn from recent years is that we need to be better prepared for future crises including outbreaks and pandemics.",,2024,Radboud Universitair Medisch Centrum,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",,2023 +P29333,1.04302E+13,Research on resilience and health of adolescents during COVID-19: Project EMPOWER (Elevating Mental and Physical Overall Well-being and Enlarging Resilience),"The mental and physical health of young people has deteriorated due to the COVID-19 pandemic. To reduce the negative effects on health, it is important to strengthen the resilience of young people. We want to do this by looking at which factors contribute to this. We hope to discover which factors contribute to resilience, so that they can be used more to help young people. We also want to discover which groups of young people had a more difficult time during the pandemic, so that extra support can be given to them. This is important so that professionals know how to best help young people in times of crisis. In addition, it also provides young people with knowledge about which factors can help them to increase their own resilience and health. Parents of young people can help them with this. We carry out this project by looking at existing data from questionnaires and interviews.",,2024,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29334,1.04304E+13,Model Predictive Pandemic Control,"During the COVID-19 pandemic, governments found it difficult to choose measures to limit the spread of COVID-19. The measures also differed greatly: from mouth and nose masks and keeping distance to closing sectors. These measures were often introduced too late, so that stronger additional measures were needed to relieve the burden on healthcare, which subsequently had negative effects on society. It is therefore important to determine at what time which measure should be introduced.",,2024,Technische Universiteit Eindhoven,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Infection prevention and control,"Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures",2023 +P29335,1.04303E+13,Excess mortality during and after the Covid-19 epidemic: a closer look at vulnerable groups,"The excess mortality during and after the corona epidemic can have several causes: the disease itself, but possibly also delayed care and government measures. The excess mortality is still persisting, which is because people are still getting Covid-19, but it can also be due to long-term consequences of the disease, or previously delayed care for other conditions. Data from other countries show that different groups are affected differently, and it is of the utmost importance to get a good picture of the vulnerable groups, in order to learn for future crises in healthcare. Large national and regional databases from Statistics Netherlands, general practitioners and hospitals will be analyzed by a multidisciplinary team, looking at mortality, hospital admissions, medication, previous Covid-19, vaccination, but also the influence of pre-existing conditions, socio-economic factors and region, with a focus on cardiovascular diseases.",,2024,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Epidemiological studies",Indirect health impacts | Disease surveillance & mapping,2023 +P29336,1.04304E+13,EQUalS: Mathematical modelling to inform an EQUitable and effective response to EpidemicS,"The COVID-19 pandemic has revealed long-standing inequalities: vulnerable groups have a greater, unequal burden of COVID-19 infection. Finding and addressing the key underlying differences has become a top priority in preparation for subsequent pandemics. Mathematical models were important in determining national measures, but so far no inequalities in society have been taken into account. It is difficult to properly include the causes of inequality in models.",,2025,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Research to inform ethical issues,Disease surveillance & mapping | Research to inform ethical issues related to Public Health Measures,2023 +P29337,1.04304E+13,Contributions of Indoor Social Spaces to Overall SARS-CoV-2 Transmission - Intersecting Models with Behavioral and Epidemiological Data for Informed Decision Making.,"Where we spend our time (with other people) determines how easily respiratory viruses, such as the Coronavirus, can spread. Many corona measures such as lockdowns, curfews and the partial or complete closure of public sectors are based on this. This reduces infections, but it remains difficult to predict how much these measures contribute to the control of respiratory viruses. A good relationship between effective measure and associated economic and social impact is difficult to determine.",,2024,Wageningen University & Research,,Other,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Social impacts | Economic impacts,2023 +P29338,1.04304E+13,Syndemic health inequalities during the COVID-19 pandemic: an immuno-epidemiological approach to tackle Unequal vulnerability and Unequal susceptibility in the general population (SHIELD-U²),"During the corona pandemic, people with health problems have been hit unevenly hard. Having multiple diseases (""multimorbidity"") and the sensitivity of the immune system (defense system) is important for getting a COVID-19 infection. But it is also important for recovery after a COVID-19 infection. It is still unclear whether and how these diseases and susceptibility can cause additional diseases, such as cardiovascular disease, or death after a COVID-19 infection.",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Unspecified,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29339,1.04304E+13,Using a smart wearable as an early warning system and as a tool to monitor disease severity in COVID-19 real-time in a susceptible population: a proof-of-concept study for infection with SARS-Cov2 variants or other respiratory viruses with pandemic poten,"Respiratory infections are sometimes poorly recognized in elderly people in nursing homes, because the symptoms are often different from the typical symptoms of a respiratory infection. Therefore, measuring signs of a respiratory infection, such as increased heart rate at rest, increased breathing and reduced exercise, could help in timely recognition of respiratory infections. This, together with knowledge about the pathogen, may lead to better control of outbreaks in nursing homes in the future.",,2024,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,Clinical characterisation and management,Disease pathogenesis,2023 +P29340,1.04304E+13,CoviChron: Covid-19 and Chronic illness interactions in transmission dynamics,"A COVID-19 infection is mild in most people. This is in contrast to vulnerable groups, such as people with a chronic illness. In these groups, proportionately more people are admitted to hospital and the risk of death is higher. It is important to be able to estimate how many infections and hospital admissions are expected in this group of people.",,2024,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2023 +P29341,1.04303E+13,Who counts depends on who is counted-II: COVID-19 test and vaccination statuses in relation to excess mortality in 2020/2021 among people with intellectual disabilities,"The COVID-19 pandemic has had a major impact on society and the health of citizens, and on people with intellectual disabilities in particular. Syndromes causing intellectual disability and overall more fragile health have contributed to more severe illness and death from COVID-19. But deaths from other causes have also increased more sharply among people with intellectual disabilities during the COVID-19 pandemic than in the rest of the population. Studies have already been conducted into the possible explanations for thyese differences in mortality, but until now these studies did not have access to test and vaccination data. Research with these basic variables is essential for the most complete picture possible. This can help better understand the causes of excess mortality during the COVID-19 pandemic and provide more targeted protection to vulnerable groups in future epidemics.",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity,2023 +P29342,05550322210002,Lifestyle & COVID-19: identification of the long-term impact of (residual) COVID-19 complaints on lifestyle and the effectiveness of a hospital-based lifestyle front office as referral office to community-based lifestyle interventions for COVID-19 patien,Resume,,2026,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Clinical characterisation and management",Social impacts | Post acute and long term health consequences,2023 +P29343,1.04303E+13,Paramedical Case Managers in the lead: Evaluation and optimization of a regional innovative care path post-COVID: CARE for Post-COVID,"Persistent complaints after a COVID-19 infection are diverse and are often treated by different healthcare providers. In practice, coordination between healthcare providers for patient guidance appears to be difficult. In a recently started pilot in the Nijmegen region, patients can be referred to the newly designed 'post-COVID' care path. A paramedical case manager plays a central role in this. This person is the patient's permanent point of contact, analyzes the patient's problems, coordinates the necessary care and organizes interdisciplinary consultations. The objective of this application is to evaluate this care pathway by measuring clinical outcome measures, patient satisfaction and the experiences of healthcare providers. In addition, healthcare consumption is mapped. Based on the insights obtained, subsequent participatory action research will take place in which the care pathway is optimized and adapted to patient needs.",,2025,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Post acute and long term health consequences | Health service delivery | Health workforce",2023 +P29344,1.04303E+13,"The effect of socio-economic characteristics, vaccination information and geographical location on excess mortality from specific causes during the COVID-19 pandemic in the Netherlands","The effects of the COVID-19 pandemic were most severe during 2020 and 2021, leading to a substantial increase in observed mortality in the Netherlands. In this project we investigate the relationship between excess mortality and characteristics such as socio-economic variables, vaccination and neighborhood information for various causes of death. For each cause of death to be analyzed, we define a pre-pandemic mortality probability that depends on socio-economic variables. By using this as a basis for mortality during the pandemic, we can make reliable estimates of COVID-related excess mortality and determine to what extent it is related to socio-economic factors. We then apply survival models and other statistical methods to determine which factors have had the greatest impact on excess mortality. This information is valuable to better understand mortality during 2020 and 2021, but also for analysis in future years.",,2024,Universiteit van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2023 +P29345,1.04303E+13,COVID-19 vaccination and (short-term) mortality - a self-controlled case series study,"The higher-than-expected death rates during the pandemic remain - at least partly - unexplained. In this study we want to further clarify the role of COVID-19 vaccination in the observed excess mortality. Previous analyses, based on Cox regression, failed to demonstrate a causal role of COVID-19 vaccination, but could not rule out the possibility that the results could be biased by prognostic differences between vaccinated and unvaccinated people. We therefore propose to apply a recently developed method based on a 'self-controlled case series'. This method is specifically designed to quantify short-term mortality after COVID-19 vaccination. Furthermore, it is possible to compare short-term mortality risks between subgroups. The results of this study will provide a better understanding of the risks of COVID-19 vaccination, which will be important for future vaccination strategies.",,2024,Universitair Medisch Centrum Utrecht,,Human Populations,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation | Clinical characterisation and management","Adverse events associated with immunization | Supportive care, processes of care and management",2023 +P29346,1.04303E+13,"Excess mortality during the COVID-19 pandemic in the Netherlands in vaccinated and non-vaccinated individuals in the context of medical history, frailty and sociodemographic factors","In this project we investigate the role of COVID-19 vaccinations in excess mortality. We take into account important factors such as people's medical history. We use data from electronic patient files of general practitioners of approximately 8% of Dutch people. We link this data at patient level to data about COVID-19 vaccination, COVID-19 testing, causes of death and personal data. We compare the observed mortality in 2021 among people who have and people who have not been vaccinated with the expected mortality. We distinguish between type of vaccine, number of vaccinations, medical history, vulnerability (in the elderly) and social demographic characteristics. The results of this study are important in the evaluation of (the safety of) vaccines and can be used for decisions regarding future vaccination policy and for information provision about vaccination.",,2024,Nivel,,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Vaccines research, development and implementation | Epidemiological studies",Disease susceptibility | Impact/ effectiveness of control measures,2023 +P29347,1.04303E+13,The impact of vaccination on inequalities in years of life lost due to Covid-19,"The Covid-19 pandemic has had a disproportionate impact on the mortality of persons with low socio-economic status. It is unclear to what extent this unequal impact depends on differences in vaccination rates and pre-existing differences in health. However, this is relevant for policy. In this project we will a) estimate the interaction between pre-existing differences in health, vaccination and socio-economic status with regard to Covid-19 mortality b) develop a simulation model to generate estimates of years of life lost due to Covid-19 mortality by socio-economic status in various scenarios c) compare the outcomes of the scenarios in terms of years of life lost and their socio-economic distribution.",,2024,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping,2023 +P29349,1.04301E+13,A Fibrosis Lung-Chip model to study development and therapy of COVID-19 post-ARDS pulmonary fibrosis,"The development of severe COVID-19 is associated with significant lung damage, in which connective tissue formation (fibrosis) can be observed in the lung tissue. This only happens in patients with a very serious course of illness, who usually receive mechanical ventilation in intensive care. In addition to the viral infection, mechanical ventilation may also be a risk factor for fibrosis development.",,2025,Leids Universitair Medisch Centrum,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation",Disease models | Disease pathogenesis | Pre-clinical studies,2023 +P29350,1.04301E+13,Human Mucosal Immune System Model Guiding Treatment Choices in COVID-19,"The elderly and people with weakened immune systems can still become seriously ill or even die from the coronavirus. In addition, up to 15% of people who have recovered from a COVID-19 infection develop a chronic condition also called 'long COVID'. Common symptoms of this condition include persistent (3 months or more) fatigue, shortness of breath, or headache. Long COVID symptoms can affect daily functioning. Treatment options for both acute COVID-19 and long COVID are limited. The researchers will develop a cell platform consisting of airway cells and blood from lung COVID patients. Instead of using animal models, this platform will help test the efficacy and safety of existing and new medicines for the treatment of (lung) COVID-19. This model offers the opportunity to predict individual drug response and develop a tailor-made effective therapeutic intervention.",,2025,Amsterdam UMC Locatie AMC,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics",Disease models,2023 +P29351,1.04303E+13,"DECIM: Investigating the drivers of excess mortality during the Covid-19 pandemic in the Netherlands, an integrated dynamic model to assess the impact of vaccination and infection","More people have died during the Covid-19 pandemic than expected based on historical death data. This excess mortality can largely be explained by infections with Covid-19, but other causes also play a role. In this study, we want to use an advanced model to investigate what these causes were and which population groups were at greatest risk. We look at the entire Dutch population aged 65 and older in 2020-2021. We calculate the difference in excess mortality between people who were and were not infected, and who were and were not vaccinated. We also investigate which causes of death occurred more or less often than normal. This research is possible because linked data has now become available for the first time. This information helps to better identify the health risks that the Covid-19 pandemic has entailed and continues to entail, so that they can be taken into account in preparations for new pandemics.",,2024,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P29352,1.04301E+13,Personalised targeted immunomodulation in patients with ARDS related to COVID19 and future pandemic pathogens (COMODULATE-project),"Goal Seriously ill corona patients receive anti-inflammatory medication in the hospital to control the immune response of their immune system. There are a number of medications for this, with different mechanisms of action and costs. During the corona pandemic, many corona patients received multiple anti-inflammatory medications, while in some patients certain specific and expensive medications proved to be less effective due to differences in immune responses. This project aims to gain knowledge about immune responses. Research design By looking back at a database with blood and saliva samples taken from corona patients, we want to investigate whether we can properly distinguish immune responses with a blood test at the bedside in the future. We also want to investigate whether there are substances in the blood and saliva that give rise to more targeted treatment. This knowledge about differences in immune responses and medication may also be applicable to subsequent pandemics not caused by the coronavirus. Executive parties Amsterdam UMC, Erasmus MC, Leiden University Medical Center (LUMC), Reinier de Graaf Gasthuis and Antonius Hospital. Context This research is one of the studies in the field of research into optimal medical specialist care for COVID-19. The aim of the studies is to answer important knowledge gaps in the field of treatment. ZonMw facilitates these studies in the COVID-19 Treatment sub-programme to contribute to promoting optimal care for COVID-19. The knowledge gaps have been identified by the Multidisciplinary COVID-19 Science Committee of the Federation of Medical Specialists (FMS). More information Main applicant: Dr. H. Endeman (Erasmus MC) Project leader and secretary: Dr. L. Bos (Amsterdam UMC)",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Therapeutics research, development and implementation","Diagnostics | Supportive care, processes of care and management | Pre-clinical studies",2023 +P29353,1.03901E+13,Infection prevention within VVT,"Working hygienically is important to prevent virus outbreaks. This has proven to be extra important during the COVID-19 pandemic for vulnerable people in nursing homes and home care. In long-term care, there is little insight into the benefits (expressed in terms of money, client safety and quality of life) of infection prevention measures. The costs are better visualized as expressed in euros, among other things. This means that an important piece of information, necessary for making organizational choices in the field of infection prevention, is missing. Insight into both the benefits and costs of infection prevention leads to better-considered decisions about the use of (scarce) people and resources. Within this consortium we combine the available expertise from Amphia Hospital, Resizto and Avans University of Applied Sciences to work on concrete outcome measures that will provide insight into the effectiveness of infection prevention within nursing home and home care.",,2023,Avans Hogeschool,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Infection prevention and control | Policies for public health, disease control & community resilience | Health Systems Research",IPC in health care settings | Policy research and interventions | Health financing,2023 +P29354,07420132210010,Always connected; in a hybrid peer environment,"Peer support contact has almost ""stagnated"" for all patient organizations in the past two years. Our own research - in a panel of approximately 1000 patients - shows that loneliness has increased enormously among breast cancer patients and that peer support contact for breast cancer is desired by 80% of the supporters. By creating new forms of informal care (hybrid), we continue to connect peers in a sustainable manner. This is relevant for breast cancer, because of the long and intensive treatment and aftercare process of at least 1 year and with major late consequences. In this project, we create new forms of hybrid peer support contact that match personal preferences and that can be used by many patient organizations. This concerns 17,000 patients with breast cancer who can participate in peer support contact as easily as possible (again), take more control of their own lives, which gives ""living with a condition"" in the post-COVID era a necessary positive boost.",,2024,Borstkankervereniging Nederland,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29355,1.04302E+13,Preclinical development of an antiviral small molecule drug against COVID-19,"The recent COVID-19 pandemic has shown how vulnerable we are as a society and how difficult it is to defend ourselves against infections with new types of viruses. SARS-CoV-2 has not been eradicated by vaccinations and some patients suffer from severe COVID-19 and/or long COVID symptoms. However, the (preventive) use of antiviral medicines to treat these patients is still limited. In this project, subsidized by ZonMw, Radboud University, Protinhi Therapeutics and Artemis Bioservices will improve viral control by developing an innovative antiviral agent. This medicine targets viral proteases, enzymes that are crucial for the replication of the virus once it has entered the body. Since viral proteases are highly conserved among coronaviruses, the project will also contribute to pandemic preparedness against future coronavirus outbreaks.",,2025,Radboud Universiteit Nijmegen,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Therapeutics research, development and implementation",Pre-clinical studies,2023 +P29356,1.04304E+13,Developing and testing behavioral interventions to prevent contamination and spread of COVID-19,"Introduction and objective The COVID-19 pandemic has had major consequences for Dutch society. During the pandemic, a lot of research has been done to monitor and explain behavior, but little research has been done into the effect of interventions to encourage compliance with measures. We are investigating how compliance with COVID-19 rules of conduct can be encouraged to prevent contamination and spread of SARS-CoV-2. The project focuses on measures that are always important, with a low-risk scenario (testing, hygiene) and high-risk scenario (keeping distance, face masks). Plan of approach Three research methods are used: 1. Analysis of existing video recordings. We examine previously collected video observations in Amsterdam to investigate, among other things, the effect of warning signs regarding keeping your distance and wearing a face mask (mouth and nose mask); 2. Online experiments. We compare eight different information strategies that have been little researched/compared in the COVID-19 context; 3. Experiments at universities, in residential areas and shopping areas. We focus on the little-researched effect of communication (via different media/channels) combined with environmental interventions, which should make certain behavior easier (e.g. free and visible self-testing, clear stickers/posters at locations of hand gel and soap dispensers). ). If a high-risk scenario arises again during the research period, we will compare the effect of different warning signs in Amsterdam. The project shows which communication strategies are most effective to encourage compliance with the COVID-19 rules of conduct. The research also examines whether communication strategies together with environmental interventions have additional value. The results are shared with policymakers and behavioral and communications staff from ministries, municipalities, and GGDs, among others, and are also useful for future outbreaks of the coronavirus.",,2024,Universiteit van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience",Communication | Approaches to public health interventions,2023 +P29357,05160482250002,Follow-up care after treatment for gynecological cancer - could it be less?,"After cancer treatment, patients receive frequent check-ups, also known as follow-up care. The purpose of these checks is to detect recurrence of disease and provide aftercare. The same schedule of checks is followed for gynecological cancer (cervical, uterine, labia and ovarian cancer). There is little evidence as to whether this schedule is best. During the COVID-19 crisis we were forced to cancel many appointments. As a result, patients have had fewer checks or in a different form, for example by telephone. Goal In this project we investigate what exactly follow-up care looked like during the corona pandemic, and what its effect was. Did it take longer before recurrence of illness was detected? And what were the patients' experiences? We want to learn more about what is important in follow-up care: what do patients really need and how should we organize this? Method We will analyze existing data from the cancer registry and from health insurers and hold group interviews with patients.",,2025,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29358,1.04303E+13,The Effect of Delayed Cancer Screening on Stage Shift and Increased Mortality during the Coronapandemic in The Netherlands,"We investigated to what extent the temporary stop of cancer screening (breast cancer, colon cancer and cervical cancer) during the Covid-19 pandemic contributed to excess mortality in 2020 and 2021. Based on a lot of data (all open), we concluded that it is highly unlikely that this temporary screening stop had a significant effect on excess mortality in the period mentioned. The cause of this excess mortality must therefore be sought elsewhere. We were able to draw this conclusion based on a careful analysis of the available data. We emphatically do not claim that the screening stop has not been without consequences for anyone: we were not able to use data at patient level, so we cannot draw such a conclusion. We do not comment on the consequences of the screening stop in the longer term.",,2023,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29359,1.04304E+13,Preventing the Spread of Infectious Diseases: A Serious Game,"Introduction and objective It is challenging for people with low health literacy - described in this project as people who participate in practical education and/or mild intellectual disability (LVB) - to adhere to measures against an infectious disease such as COVID-19. There is a need for appropriate behavioral interventions that take into account the challenges and complexity of this group. Playing a serious game is a promising intervention to promote COVID-19-related preventive behavior. Playing a serious game can increase awareness, support and willingness to apply certain behavioral measures. The aim is to use an existing, adapted serious game to support people with low health literacy in carrying out prevention measures. This increases support and willingness among vulnerable target groups to take appropriate measures themselves and to adhere to them. Plan of approach We focus on people with MID and students in practical education. The project has a mixed method design and consists of three phases: 1) further development of the serious game in co-creation with the target group and pre-testing of the game; 2) playing and evaluating the effects of the game; 3) evaluation of the process and further implementation. The project combines different theories to gain insight into pre-motivational factors and post-motivational factors. This also aims to achieve the step of converting intention into action. This intervention is evaluated for effectiveness with a control group. Expected outcomes: 1) Development of different scenarios tailored to vulnerable target groups for the serious game; 2) Intention to perform preventive behavior after playing the game; 3) Procedure improvements for serious game adjustments and collaborations with experienced experts. The project further looks at underlying determinants of intention and behavior, health literacy and the prevention of infection and spread of an infectious disease such as COVID-19.",,2024,Verwey-Jonker Instituut,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2023 +P29360,1.04301E+13,BREAK COVID: COVID-19 breakthrough infections and correlates of protection,"BREAK COVID: breakthrough infections and correlates of protection At this stage of the pandemic, almost everyone has built up immunity against SARS-CoV-2. However, breakthrough infections are often seen after vaccination or natural infection. Breakthrough infections can be contagious, pose a risk to vulnerable people and can also lead to long-term complaints (post-COVID). In particular, the cellular defense could play an important role against breakthrough infections with virus variants. LUMC researchers will study which parts of the defense offer protection against breakthrough infections. More than 40 cellular immune markers will be measured in individuals with and without breakthrough infections. The aim is to identify 3-5 key markers that are predictive of protection against breakthrough infections. The findings will contribute to estimates of the risks of breakthrough infections in the Dutch population and can be used to optimally design the vaccination policy.",,2023,Leids Universitair Medisch Centrum,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Prognostic factors for disease severity,2023 +P29361,05160482240003,Substitution of care within benign gynecology during the COVID-19 pandemic in the Netherlands,"During the COVID-19 pandemic, less surgery was performed than before (or after). Elective care surrounding benign diseases has been particularly hard hit; after all, priority was given to acute and oncological surgery. In benign gynecology, surgical elective care has virtually come to a standstill. It is obvious that alternative treatments have been offered to these patients during the COVID-19 period. Purpose and method With this research we will find out which care was provided instead of operations and how satisfied patients and caregivers were with this. With this information we can draw up a protocol for which care should be offered and how in a new period of absolute scarcity. But even in the case of relative scarcity, one can learn from substituted care: if patients are equally satisfied with non-operative treatment, operations may be performed less frequently. This can contribute to lower healthcare costs and relieve the burden on staff.",,2025,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29362,50-56300-98-231,Validating the Corona Check app-based triaging service and promoting optimized use in future COVID-19 waves,Not available,,2024,Universitair Medisch Centrum Utrecht,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Health Systems Research,,2023 +P29363,1.04303E+13,Excess mortality during the Covid-19 epidemic: vulnerable groups and long-term effects,"6 million people have died worldwide from Covid-19. In the Netherlands this is 30,000. The effect of an epidemic on mortality can best be described as 'extra mortality', i.e. the total number of additional deaths during Covid-19 (2020-2021) compared to the previous years. The excess mortality is partly caused by Covid-19 (diagnosed and reported or not), but may also be due to other factors, such as less treatment for other conditions or its postponement. This may explain why there is still excess mortality, while the epidemic is in calm waters. In this project, excess mortality is mapped, with the aim of identifying vulnerable groups, both during the epidemic and afterwards. This takes into account age, gender, people who already had certain chronic diseases, and socio-economic factors and lifestyle. The aim is to limit additional mortality as much as possible in the event of a future epidemic.",,2023,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2023 +P29364,1.04303E+13,Who counts depends on who is counted: an investigation into excess mortality among people with intellectual disabilities in 2020-2021,"People with intellectual disabilities have been proportionally more affected by the COVID pandemic than the general population. In 2020 and 2021, at least 785 people with intellectual disabilities died from COVID, while 180 deaths were expected based on the size and age structure of this group. In addition, mortality from other causes also increased more than in the rest of the population. Data from general practitioners showed that deaths in this group were more often due to a chronic disease, but that this was not a complete explanation for the higher mortality in this group. Intellectual disability also remained an independent risk factor for death. This indicates that health problems of people with intellectual disabilities are complex. There is still no complete insight into the actual number of infections in this target group and therefore the knowledge is still incomplete to reduce risks in the future.",,2023,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity,2023 +P29365,1.04303E+13,Providing context to excess mortality through changes in healthcare use during the COVID-19 pandemic,"Significant excess mortality has been reported during the COVID-19 pandemic. A large part can be explained by mortality caused by the virus itself, but there are many other possible causes for deviations in mortality. For example, there has been a decrease in traffic fatalities, but there may have been an increase due to late or undiagnosed diseases. Such patterns have been clouded by changes in overall mortality statistics. Additional data is needed to better explain excess mortality. In this study we offer additional tools to explain excess mortality by looking at changes in healthcare use, also within different groups. Based on health insurance data, we can compare healthcare use in 2020 with expected healthcare use based on previous years. For example, which operations were performed more or less often. Such insights contribute to a better understanding of excess mortality during the pandemic, but also possible future excess mortality due to missed care.",,2023,Amsterdam health & technology institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures | Health Systems Research",Impact/ effectiveness of control measures | Disease surveillance & mapping | Indirect health impacts | Health service delivery,2023 +P29366,1.04303E+13,Using individual level survival prediction to estimate years of life lost due to Covid-19 and their socio-economic distribution,"Several studies suggest that mortality due to Covid-19 is concentrated among people with a low socioeconomic status. The extent to which this socioeconomic inequality in mortality translates into an inequality in years of life lost is largely unknown because years of life lost are highly dependent on underlying health conditions. Using administrative data, we estimated individual-level survival probabilities for the Dutch population, using predictors such as medication use, hospital and nursing home admissions, disposable income, gender and age. Using the estimated model, we predicted years of life lost for those who died from Covid-19. Results from our analyses show that there is a huge variation in years of life lost across the population, suggesting that not only the vulnerable and sick died from Covid-19. Differences in the burden of disease due to Covid-19 by income are caused by differences in the number of deaths, and not by the number of years of life lost per death.",,2023,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2023 +P29367,1.04301E+13,"Vital, resilient and full of energy hybrid work","Hybrid working has been embraced within the provincial sector since the Covid-19 pandemic. But how do you, as an employee, deal with the balance between work and private life, your own wishes and interests versus the interests of your team and organization and the workload you have to deal with? With individual coaching programs we want to support hybrid employees to work on their resilience and vitality, so that they can (continue to) do their work in a hybrid environment with pleasure and energy. These processes are carried out by Noloc and Nobco accredited coaches. In this way, we expect to increase the mental vitality of hybrid workers at least at an individual level.",,2024,A&O-fonds Provincies,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2023 +P29368,1.04303E+13,Determinants of excess mortality rates in nursing homes,"High mortality rates in nursing homes are an important topic in both political and social discussions during the COVID-19 pandemic. This project investigates the role of organizational characteristics of nursing homes (such as staffing, quality and size) in explaining excess mortality during the pandemic. For this we use data from all nursing home residents in the Netherlands, linked to information about the nursing homes. In addition, we investigate whether organizational characteristics have contributed to (possible) income-related inequality in excess mortality among nursing home residents. Finally, we highlight the extent to which excess mortality in nursing homes can be explained by the excess deaths directly related to COVID-19 infections, or to the indirect consequences of the pandemic, such as absenteeism. Our results provide insight into how excess mortality, and inequality thereof, can potentially be reduced during outbreaks of infectious diseases.",,2023,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2023 +P29369,1.04304E+13,The role of cleaning and disinfection of the environment and the use of long-sleeved gowns to prevent nosocomial transmission of pandemic viruses: the ENVI-GO-PAN project,"Introduction and objective National and international guidelines on SARS-CoV-2 recommend not only cleaning but also disinfecting surfaces in a patient room after a patient with COVID-19 has been discharged. The use of disinfectants is a measure to prevent infections. It also entails high costs, extra work and health risks for healthcare workers. In addition, potentially harmful substances end up in the environment. Wearing an isolation gown while caring for a COVID-19 patient is also recommended in the guidelines. The use of aprons leads to high costs, extra work and a lot of waste. The rationale for both measures is now 'better too much than too little', but with very little evidence. There is a need for more knowledge. The aim of the ENVI-GO-PAN project is to determine the role of cleaning and disinfection for patient room surfaces for SARS-CoV-2, but also for influenza (virus with the potential to cause a pandemic) and respiratory syncytial virus (important virus in the hospital). The added value of aprons during care for COVID-19 patients is also assessed. Plan of approach For the first objective, a national questionnaire is distributed, a systematic literature search is carried out and a laboratory study is carried out. For the second goal, the project will conduct a systematic literature review, a laboratory study and possibly also a study examining gowns used in patient care. The ENVI-GO-PAN project will provide evidence-based advice for the use of disinfectants for respiratory viruses and the use of gowns for COVID-19 patients. Because the project does not only look at the SARS-CoV-2 virus, the results will be important for a broader group of respiratory viruses and also in future pandemics.",,2024,Erasmus Medisch Centrum,,Human Populations | Environment | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings",2023 +P29370,1.04303E+13,Knowledge exchange platform for COVID-19 recovery and aftercare,"A significant group of people experience long-term complaints after a COVID-19 infection. The guideline 'Long-term complaints after COVID-19' has taken an important step in bundling available knowledge. It is a new disease that affects a large group of people in multiple organs and in a large number of people's domains (private, work, etc.). A large number of organizations are involved in recovery and aftercare. The risk is that cooperation and coordination are not sufficiently structured. This proposal focuses on establishing the ""platform for recovery and aftercare for persistent complaints after COVID-19"", to bring together the most important organizations in a structured manner. And to contribute to knowledge sharing, joint mapping of bottlenecks to be addressed and mutual coordination. The platform contributes to better use of the power of the organizations involved and thus indirectly to better support for those affected.",,2025,Long Alliantie Nederland,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2023 +P29371,1.04303E+13,Lifestyle and excess mortality during the COVID-19 pandemic,"During the COVID-19 pandemic, there is excess mortality in the Netherlands. It is unclear what the cause is. This research focuses on the influence of lifestyle on the chance that a person will die during the pandemic. Two possible causes of death are central: death due to a COVID-19 infection and death due to a deteriorating lifestyle during the pandemic. We calculate the chance of dying from both causes. In this way we determine the effect of lifestyle factors on the risk of mortality and excess mortality before and during the pandemic. Our results can be directly used to understand the causes and consequences of excess mortality in the Netherlands. In the future, they can be used to investigate the effects of new mutations of the COVID-19 virus or to evaluate the effects of lifestyle policies on health more generally.",,2023,Stichting Economisch onderzoek,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Disease pathogenesis,2023 +P29372,1.04303E+13,Covid-19 lockdown and its impact on mortality rate in Alzheimer's - the CORAL project,"The patients who attended the memory clinic during the Corona lockdown have been compared with historical control patients. A higher risk of mortality is seen in memory clinic patients who have experienced the pandemic, especially patients with dementia and especially patients who were admitted to a nursing home. When comparing causes of death between pandemic patients and historical controls, we see a higher mortality rate in pandemic patients for death due to COVID-19 infection and other causes of death (including external cause of death). A lower mortality rate in pandemic patients is seen for death from neoplasms and cardiovascular diseases. Only the difference between pandemic patients and historical controls for death from COVID-19 infection is significant. We do not have an estimate of healthcare use during the entire COVID-19 pandemic. Nevertheless, we analyzed healthcare costs from 2015-2020, which showed that our pandemic patients had significantly lower healthcare costs in 2020 compared to historical controls in 2018.",,2023,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P29373,1.04303E+13,Excess mortality during the COVID-19 pandemic in the Netherlands: associations with people's medical history and sociodemographic characteristics,"During the COVID-19 pandemic, there was a 3.3% increase in mortality compared to before the pandemic. This is why we speak of excess mortality. Nivel investigated this using existing data sources, such as data from general practitioners, on death and personal characteristics. Excess mortality occurred mainly during the various periods in which the number of COVID-19 infections increased and among people aged between 65 and 74, compared to the 5 years before the pandemic. People with a non-Western migration background and people with a low household income were hit hardest by this, especially if they also had one or more health problems. The COVID-19 pandemic has had a greater effect on the risk of death among these groups compared to the general population. This emphasises the need to better protect vulnerable people against death in general and specifically during periods in which our public health is threatened, such as during the COVID-19 pandemic.",,2023,Nivel,,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Vulnerable populations unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Epidemiological studies",Indirect health impacts | Disease surveillance & mapping,2023 +P29374,1.04303E+13,Healthcare avoidance and excess mortality during the COVID-19 pandemic in the Netherlands: a population-based cohort study,"During the first phase of the pandemic, one in five people did not go to the doctor. In addition, healthcare providers have postponed and/or postponed appointments due to COVID-19. It is unclear to what extent this (perceived) change in access to care has contributed to the observed excess mortality in the Netherlands in 2020-2021. In this population study we answer the following research question: What is the relationship between care avoidance during the first phase of the corona pandemic and observed mortality? In response to this research question, we use previously distributed questionnaires among 5,656 patients to determine to what extent reported care avoidance during the first phase of the pandemic is related to mortality.",,2023,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Policies for public health, disease control & community resilience","Supportive care, processes of care and management | Approaches to public health interventions",2023 +P29375,1.04301E+13,Setting up an organization and infrastructure for cross-research group analyzes of COVID vaccine immune response (Harmony project).,"A large part of the Dutch population has been vaccinated against COVID-19. After vaccination, an immune response follows in the body. This is how immunity is built up. However, some people have a reduced immune system. This may be due to underlying conditions such as an innate immune disorder. Or by treating a disease. These people are at a higher risk of problems with a COVID-19 infection. We do not yet know well enough whether they are protected sufficiently and for a sufficiently long time after vaccination. With the help of this project, conditions are being set up under which data sharing between nine different research groups can take place in a good and safe manner. It is also ensured that everyone speaks the same language. A solution is being sought for all organizational and technical challenges that arise. This should lead to answers to research questions so that more people are better treated and protected in the event of a COVID-19 infection.",,2024,Rijksinstituut voor Volksgezondheid en Milieu,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Data Management and Data Sharing,,,,,"Vaccines research, development and implementation | Pathogen: natural history, transmission and diagnostics",Characterisation of vaccine-induced immunity | Immunity,2023 +P29376,1.04301E+13,Nasal And Systemic Immunity following COvid VACcination (NASI-COVAC),"The immune system against respiratory infections is often studied in the blood, while viruses such as corona enter through the nose. The aim of this project is to gain insight into the immune system in the nose after a coronavirus infection or after repeat vaccinations. To this end, in this project, small amounts of immune cells are collected from the mucous membrane of the nose using a new method that causes minimal burden for the patient. Antibodies collected from the nose will also be measured. This research can show whether protection is built up in the nose after infections with corona (SARS-CoV-2) or repeat vaccinations. The effectiveness of the built-up defense against new variants will also be examined. Finally, the use of animal models will investigate which immune cells, and in which location, are needed for protection against infection after vaccination.",,2023,Leids Universitair Medisch Centrum,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P29377,1.04301E+13,'VIP culture' in the nursing home - working together on mental vitality at organizational level,"Mental vitality (MV) is important for effective and sustainable functioning organizations. Due to increasing demand for care, staff shortages and covid, MV, especially in nursing homes, is under pressure. In this project we will apply and investigate the promising intervention 'Vitality in Practice Culture' (VIPc) in 2-3 nursing home organizations. VIPc works with the combination of a representative working group and larger group meetings. With a regional learning network and a sounding board group, we promote learning among each other and outside the project. The evaluation action research is used as a flanking element of the intervention. Evaluation, improvement, learning and knowledge development therefore go hand in hand in a participatory, cyclical and reflexive process. With the aim: an organizational culture in which MV is openly discussed, with active involvement of employees in MV, knowledge within organizations about (promoting) MV, social cohesion and learning ability about what works for maintaining MV.",,2023,ZWconnect,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Health Systems Research | Research on Capacity Strengthening,Health service delivery | Cross-cutting,2022 +P29378,1.04301E+13,"Mental vitality in the workplace, from data to action!","GROBA is a pioneer in the development and production of machines for the cheese processing industry. The organization strives to increase the mental vitality and psychological health of its employees. GROBA wants to achieve this goal in an innovative and practical way by activating employees in an inspiring way and guaranteeing all acquired knowledge and changes. The Covid-19 circumstances pose an additional challenge, and GROBA recognizes the urgency to strengthen the vitality of its employees, taking into account the stress these circumstances have brought about. Goal The main objective of this project is to promote the mental vitality and resilience of GROBA employees, with specific attention to dealing with the consequences of the Covid-19 pandemic. Minimizing psychological failure and turnover is central. Approach/method By combining data analysis and action learning, insights are gained into the success factors regarding mental vitality and resilience within the organization to increase the psychological health of its employees. The integrated and sustainable approach that contributes to mental vitality consists of 7 steps: Define scope: Clear demarcation of the project area. Activation: Activities to involve employees. Baseline measurement: Measuring current mental vitality and resilience. Data analysis: Analyzing collected data for insight. Implementation: Carrying out relevant interventions based on analyses. Measurement & realization: Evaluating effectiveness and achieved results. Consolidation & assurance: Sustainable assurance of positive changes. Collaboration partners GROBA collaborates with JECKX, a consultancy organization for sustainable employment practices, well-being and job satisfaction. JECKX has developed the program for GROBA, aimed at increasing job satisfaction and well-being. EHERO, a research institute of Erasmus University, carries out the implementation and evaluates with action research, while all acquired knowledge is shared for good practices. (Expected results By implementing this approach, GROBA expects a significant improvement in the mental vitality and resilience of its employees. The project aims to reduce psychological dropout and have a positive influence on the retention of employees within the organization. More information News item: Groba is committed to strengthening the mental vitality of employees",,2023,GROBA B.V.,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P29379,1.04301E+13,The bright side of work: Increasing work engagement of TU/e employees with top-down and bottom-up interventions,"The TU/e ​​employees are under pressure. In a scientific context with pressure to perform excellently and the aftermath of the COVID-19 crisis, the workload, leadership issues and inclusion and social safety issues also have an impact on the mental vitality (i.e. enthusiasm) of these employees. To strengthen their enthusiasm, we integrate e-interventions into the employee experience survey (EES) process. We are developing a methodology to interpret the results of the EES and then convert them into targeted actions. In this way, top-down solutions can be found that support employee enthusiasm. At the same time we open the bottom-up channels using online training tools for employees and managers to encourage employees to organize their work in such a way that they are mentally fit, enthusiastic and resilient. These top-down and bottom-up interventions will together deliver useful solutions that contribute to mentally fit employees.",,2023,Technische Universiteit Eindhoven,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P29380,1.04301E+13,AMOUR: Action research on mental support for elderly care,"After the COVID-19 pandemic, absenteeism increases due to: mental problems, sleep disorders, recurring fears and thoughts, increased irritability, worries about the future and reduced activity level (Beck, 2011; Da Silva et al., 2021). In addition to the expected trends within this sector: double aging, labor market tightness and a more complex care need (source: FWG), the importance for VVT organizations to focus on employee retention becomes clear. Offering peer support (CO) to caregivers has proven to be an effective way of providing such mental assistance. Action research (AO) has proven to be a successful approach to implementing complex changes and interventions. In addition to evaluating the implementation, AO offers the opportunity to develop knowledge. Knowledge about both success and failure factors as well as effectiveness that can be useful for the entire VVT ​​and Activite offers a basis for making policy on (perpetuating) CO after this project.",,2023,ActiVite,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P29381,1.04303E+13,Individual and environmental determinants of differences in excess mortality between neighbourhoods in Amsterdam during the COVID-19 pandemic,"There was excess mortality in Amsterdam in 2020 and 2021, more people died than in 2018 and 2019. In this study we looked at which personal and environmental characteristics can explain differences in mortality. There was excess mortality, especially for people over 70, men, and people with a migration background. There were also strong differences between the 22 city areas, but there seemed to be no clear connection between excess mortality during the first, second and third waves of the pandemic. Higher excess mortality was also found in neighborhoods outside the ring road as well as in central neighborhoods. We also found that neighborhoods with more residents aged 65 and older, on average larger households, and more air pollution had a higher chance of excess mortality. Neighborhoods with more general practitioners, more green outdoor space and a higher socio-economic status actually had a lower risk of excess mortality. This research underlines the call for more action to reduce health disparities.",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2022 +P29382,07420132210030,Post Covid NL: online information and digital contact with fellow sufferers,"Post Covid Tens of thousands of Dutch people with long-term complaints after a corona infection are struggling with a clinical picture about which much is still unclear. Often they have not yet been able to resume their old lives. The recovery is difficult and they have major concerns about their future, their work and income. Acceptance (also by those around them) is difficult. The large group of people with Post-Covid complaints appears to benefit greatly from regular digital contact with fellow sufferers and from accessible, online access to reliable information from experts. This contributes greatly to their well-being and supports them on the road to recovery. The busy digital platform PostCovidNL.nl, an initiative of Longfonds in collaboration with other health organizations, meets the needs of the ever-growing group of patients with PostCovid. The approach appears to be very effective. That is why this project focuses on the important sustainable further development of the platform.",,2023,Longfonds,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Indirect health impacts",2022 +P29383,1.04301E+13,Working on your vitality,"The corona pandemic has increased workload in education. The employees had/are dealing with corona among students and colleagues, which meant that a lot of work had to be done online and new methods and working methods had to be developed, creating a new situation due to working from home. There are also employees with long Covid complaints. Many staff were concerned about students' welfare and progress. In all situations this can lead to less vitality at work. The target group for the use of guidance is working people in general. The intervention is supervised by an accredited registered career coach (NOLOC) and an accredited lifestyle coach (BLCN). The intervention consists of vitality questionnaires, group meetings, individual coaching and assignments. Expected results are: providing self-direction and mental vitality. Employees work on energy and motivation levels, reduce work stress and mental balance.",,2023,CPOZ,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P29384,1.04301E+13,Development of a unique in vivo model for long-COVID to test and identify candidate drugs,"After a coronavirus infection, 10-30% of people continue to have complaints for a long time (months to years). This is called Long-COVID or post-COVID. Worldwide, Long-COVID has a major impact on both the lives of these people and society as a whole, including long-term disability. Unfortunately, there is currently no medicine available. The aim of this project is to develop an animal model for Long COVID. This model gives global research into Long-COVID therapy an enormous boost because it (1) Provides insight into the underlying cause of Long-COVID (2) Provides the opportunity to test possible candidate drugs in the future (3) An objective diagnosis for Long COVID possible (4) Pandemic preparedness supported, because future coronaviruses (just like SARS and MERS) will probably also cause long-term complaints.",,2025,Amsterdam UMC Locatie AMC,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Post acute and long term health consequences,2022 +P29386,1.04304E+13,Covid-19 and Influenza: appropriate measures to prevent and control outbreaks in nursing homes,"Introduction and objective Since the spring of 2020, nursing homes have been hit hard by COVID-19 in several areas. Various preventive measures have been implemented to prevent contamination and spread of COVID-19. In addition to advantages in the field of infection prevention, these measures also have disadvantages in terms of perceived quality of life for residents and loved ones, and perceived quality of work for healthcare professionals. The current project aims to provide insight into what an appropriate range of measures is to prevent or combat outbreaks of COVID-19 and Influenza in nursing homes. 'Appropriate' means: both useful to prevent/control an outbreak and proportionate with regard to quality of life and work. Plan of approach The project consists of three pillars: This pillar uses a survey among at least 30 nursing home organizations to map out how they have prepared for outbreaks of COVID-19 and Influenza in the autumn and winter of 2022/2023; This pillar monitors nursing home organizations where an outbreak of COVID-19 or Influenza occurs. It is examined to what extent it is possible to successfully implement the previously developed strategy for infection prevention and control, and what the promoting and hindering factors are; In the final pillar, focus groups are held with residents, relatives and healthcare professionals to gain insight into the support for the various infection prevention and control measures in different outbreak scenarios. The results of the three pillars are combined and processed into advice for appropriate measures to prevent and control outbreaks of COVID-19 and Influenza in nursing homes.",,2024,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Infection prevention and control,Disease transmission dynamics | Impact/ effectiveness of control measures | IPC in health care settings,2022 +P29387,1.04304E+13,VIMP I: Animated Video Including Online Meetings & VIMP II: Nonviolent Communication for People with Visual and Visual-Auditory Impairments,"This project is a follow-up to the research 'The impact of the corona measures on the psychosocial well-being of people with a visual or visual-auditory impairment' (COVID-19 program, AG3). The results of this research are products that contribute to better psychosocial well-being for people with a visual or visual-auditory impairment (V(A)B). In work package I, an animated video is being developed to encourage working from home as much as possible for people with V(A)B and, in particular, to make online meetings as inclusive as possible. This video provides insight into what it is like to meet online with V(A)B and tips to make online meetings more inclusive. In work package II, existing GC training courses are made inclusive for people with V(A)B, so that they can benefit from communicating according to the ideas of GC. We want to achieve this by developing guidelines for GC trainers to make their training inclusive for people with V(A)B. When developing the various products, the aim is to find solutions with a sustainable character so that they can also be in force when the corona crisis is over.",,2023,Saxion Hogescholen,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health | Innovation,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2022 +P29389,1.05101E+13,Pandemic Preparedness Plan for common Neurodegenerative Diseases (PREP-ND),"During the COVID-19 pandemic, many patients with forgetfulness or movement disorders were unable or unwilling to contact their healthcare providers. This reduced accessibility to care has probably not improved the quality of life for these patients and their loved ones. Goal In this project, a working group of international experts, together with patients, draws up a plan on how we can maintain access to care for people with neurodegenerative diseases, such as dementia or Parkinson's disease, when this comes under pressure due to a (future) pandemic . Approach The working group brings together experiences and data from both general practices and hospitals to provide advice if a (corona) virus outbreak occurs. We divide this advice into three phases of the patient's journey: the phase before diagnosis has taken place, the phase of diagnosis and the phase after diagnosis. This working group converts the lessons learned into a plan in order to be well prepared for a new (wave of the) pandemic. This way, vulnerable patients continue to have access to care even during a pandemic, and scientific research into neurodegenerative diseases can continue. More information Help with dementia and corona website Alzheimer Netherlands",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29390,1.04301E+13,Dutch Police Union Vital police officers at home hybrid workers,"The police is an organization with 65,000 employees. The largest employer in the Netherlands. A lot was and is being asked of the police. People are faced with a lot, both physically and mentally. The NPB notices that after the corona period, many people need extra support and are less vital. Mental or psychological vulnerability has increased. 5 to 10% of employees are dealing with long covid. Absenteeism due to illness has increased, many police officers are walking on their toes and are at risk or have retired. Within this program we are committed to 45 police employees who mainly work from home or hybrid. We focus on strengthening the mental vitality that needs extra support as a result of the corona epidemic. The coaching will take place by registered Noloc career professionals who also have an employment expert background. Customized interventions are the basis of the program and focus on strengthening mental vitality.",,2023,Nederlandse Politiebond,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P29391,1.04301E+13,Dutch Police Union; vital police officers (target group; workers in general,"The police is an organization with 65,000 employees. The largest employer in the Netherlands. A lot was and is being asked of the police. People are faced with a lot, both physically and mentally. The NPB notices that after the corona period, many people need extra support and are less vital. Mental or psychological vulnerability has increased. 5 to 10% of employees are dealing with long covid. Absenteeism due to illness has increased, many police officers are walking on their toes and are at risk or have retired. Within this program we are committed to 45 police officers, the target group of workers in general. We focus on strengthening the mental vitality that needs extra support as a result of the corona epidemic. The coaching will take place by registered Noloc career professionals who also have an employment expert background. Customized interventions are the basis of the program and focus on strengthening mental vitality",,2023,Nederlandse Politiebond,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P29392,1.04304E+13,"Riding the waves in the pandemic tail: incidence, risk factors and impact of SARS-COV-2 reinfections","Introduction and objective Re-infections with SARS-CoV-2 occur frequently due to waning immunity after previous infection and/or vaccination and the appearance of virus variants that partially evade existing immunity. In the current phase of the COVID-19 pandemic, there is therefore still a risk of new corona waves, especially during the winter season. Better understanding of the duration of protective immunity and the risk of reinfections, including their influence on individual health, makes it possible to be better prepared for new corona waves and to target measures that limit the impact on individuals and society as effectively as possible. can take. That is why this project focuses on research into risk factors for reinfections, including possibly declining immunity against the SARS-CoV-2 virus, and into what these infections mean for health and daily functioning in the short and long term. Plan of approach This research requires studying significant numbers of people, which is possible in this project through a collaboration of 7 ongoing, so-called cohort studies in which adults and children who have experienced COVID-19 are studied. Because these people have been followed closely for a long time, a lot of important information is already known, for example about previous infections and vaccinations. In the current project, blood samples for immunological determinations and data on health and functioning are collected from approximately 1350 participants (+- 300 children, 1050 adults) of these cohorts at four 3-monthly time points. Participants are also asked to take additional respiratory samples at home for respiratory complaints in the laboratory, in addition to a corona self-test. Based on the wealth of previous data from the individual cohort studies, supplemented with this newly collected data, precise analyzes are performed to better understand the risk of reinfections and its impact on health and society. This project builds on the previous LOCOMOTION project.",,2024,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease susceptibility | Prognostic factors for disease severity | Indirect health impacts,2022 +P29393,1.04301E+13,Frequency of opportunistic pathogens in Covid-19 and their impact on clinical outcome,"An infection caused by herpes viruses or the fungus Aspergillus in the lung can occur in patients with severe COVID-19. It remains unclear how often this occurs and whether it affects the severity of the disease. Goal The aim of this study is to investigate how common an infection with herpes viruses or the fungus Aspergillus occurs in severe COVID-19, and whether this affects the severity of the disease. Research design An important cause for the development of severe COVID-19 is a harmful inflammatory response. During the pandemic it became known that inhibition of this inflammatory response was beneficial for patients with severe COVID-19. The risk of these treatments is that there may be an increased susceptibility to herpes infections and fungal infections. Through this research we want to find out how often an infection with herpes viruses or the fungus Aspergillus occurs in severe COVID-19 and whether this affects the severity of the disease. These results are needed to subsequently investigate whether treating these infections in patients with COVID-19 is useful.",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2022 +P29394,05160482220001,Care avoidance and reduced accessibility to care during the COVID19 pandemic - course and long-term effects on incidence and prognosis of cardiovascular disease and cancer in the Netherlands,"During the first phase of the pandemic, 1 in 5 people did not go to the doctor. In addition, healthcare providers have postponed appointments due to COVID-19. It is unclear whether this changed access to care has led to more serious forms of cardiovascular disease and cancer. Goal In this project we answer these questions: To what extent and by whom has less care been received? What are the effects of this on the severity of cardiovascular disease and cancer? To what extent have the conversations between doctor and patient changed as a result of the adapted care offering? Method In response to question 1, we calculate how many people visited the GP during the pandemic with complaints consistent with cardiovascular disease or cancer, compared to years before. For question 2, we look at whether more serious diagnoses have been diagnosed than before, such as metastatic forms of cancer. For question 3, we use questionnaires to investigate how the adapted care offering, such as video consultations, has influenced doctor-patient conversations.",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2022 +P29395,1.04301E+13,Overarching analyses of COVID-19 vaccination strategies in healthy and immunocompromised individuals: 'Lessons learned' from the ongoing pandemic,"More than 80% of the Dutch population has been fully vaccinated against COVID-19. Vaccinating individuals protects them from serious illness. Because the coronavirus adapts over time, protection became less. A booster vaccination was therefore offered for the first time at the beginning of 2022. The immune response induced by vaccination has been monitored in the healthy Dutch population by the Erasmus MC and the RIVM. In addition, 8 different research groups, led by medical specialists, have studied the immune response in patients with reduced immune systems. It is now possible to answer an important question: ""Which vaccination strategy provides the best defense in healthy and immunocompromised individuals."" By answering this question, advice for future booster vaccinations can be given per risk group. In addition, these lessons can be used to draw up vaccination recommendations in the event of future outbreaks.",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation","Immunity | Supportive care, processes of care and management | Vaccine trial design and infrastructure | Characterisation of vaccine-induced immunity",2022 +P29396,1.04301E+13,Working on your vitality,"As a result of the corona pandemic, the workload in healthcare has increased. The employees who worked in healthcare had and are dealing with corona among clients and colleagues, which means that they work differently around clients and that services from colleagues have to be accommodated. In addition, a new situation has arisen for some of the staff due to (partially) working from home. There are also employees with long Covid complaints. In all situations this can lead to less vitality at work. The target group for the use of guidance is working people in general. The intervention is supervised by an accredited registered career coach (NOLOC) and an accredited lifestyle coach (BLCN). The intervention consists of vitality questionnaires, group meetings, individual coaching and assignments. Expected results are: strengthening one's own control and mental vitality. In concrete terms, employees work to increase energy and motivation levels",,2023,Viazorg,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29397,1.04301E+13,"Continue actualisering van het ""Covid Outcome Prediction in the Emergency department"" (COPE) model","COPE is a model that predicts the course of the disease for COVID-19 patients presenting to the emergency department. The prediction model is based on 6 objectively measurable variables that are collected as standard in the emergency room. COPE was developed based on data up to and including August 2020. This research shows that COPE also predicts well in 2021 and 2022 which patients have a high risk of death. But the observed mortality in 2022 was 10% lower than predicted. This is likely due to new virus variants (such as Omikron) and improvements in treatment. We have adjusted the parameters of COPE in such a way that the average mortality is now correctly predicted again. We have also adjusted the COPE app so that the parameters are easy to update. In this way, we have ensured that COPE will continue to provide an accurate estimate of the severity of the disease course for COVID-19 patients in the emergency department in the future.",,2023,Erasmus Medisch Centrum,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity,2022 +P29398,1.04303E+13,Long COVID VR Rehabilitation at home (COVR2Home),"Goal The COVR2Home project investigates the effectiveness of Virtual Reality (VR) home exercises on the recovery of people with persistent complaints after COVID-19. Method Patients with physical and 'coronamist' complaints receive physical, concentration, memory, breathing and mental exercises in VR at home. This group is compared with a large group of patients in the ParaCOV study, who did 'standard' home exercises. In addition, a standard care cohort is followed in the same period as the VR cohort. Within the VR cohort, it is being explored which patient-related factors influence the effect of practicing with the VR glasses; with the aim of gaining insight into which post-COVID patient is most suitable for VR exercises at home. Expected yield With proven effectiveness and broad applicability, a VR home exercise program can be a good alternative to the current approach and contribute to person-oriented and effective care 'close to home'. Home rehabilitation with VR glasses for post-COVID-19 complaints Radboud university medical center is investigating how well Virtual Reality home exercises work for the recovery of people with persistent complaints after COVID-19. In this study they compare two treatments: the regular treatment with the physiotherapist the treatment by the physiotherapist with VR glasses, in which physical, concentration and breathing exercises are performed at home. Radboudumc also made a video about it: www.radboudumc.nl/vrbril-post-covid",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health | Innovation,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P29399,05160482130001,"COFIT-PSY project: Consequences of COVID-19 measures for health outcomes, lifestyle and recovery in people with PSYchiatric disorders","The COVID-19 pandemic has had major consequences, especially for vulnerable groups. Goal The aim of this research is to map out the consequences of the corona measures for people with serious psychiatric disorders. Method We use existing data to see whether health outcomes (mental health, perceived stress and recovery) in this group were different during the pandemic than in the years preceding the pandemic. We also conduct interviews to see how people with serious psychiatric disorders experienced the corona measures. Finally, together with experienced experts, we are developing an approach for Shared Deciding that helps people with a serious psychiatric condition to continue working on a healthy lifestyle during future lockdowns. Expected result The research will help to limit the negative consequences for people with serious psychiatric disorders as much as possible during subsequent pandemics.",,2024,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2022 +P29400,1.04303E+13,"Person-centered, integrated aftercare COVID-19 in the region (PINCOR)","More than 200,000 people have persistent complaints after a COVID-19 infection. They rely heavily on restorative care, but it is unknown whether this leads to faster healing. Goal In the PINCOR project we investigate the effect of person-oriented, integrated aftercare for COVID-19 within a regional network. Method Together with the GP, the patient determines treatment goals aimed at better functioning at home and in society. Depending on the severity of the complaints, the patient is guided by the general practice, supplemented with paramedical care (for example physiotherapy) or specialized rehabilitation care. Experiences of healthcare providers and patients are examined when designing the best approach. The patient keeps a digital diary to measure the course during and after treatment. The aim of the treatment is to increase the quality of life and participation in society and to reduce absenteeism and healthcare costs. Patient organizations and C-support are involved in the research.",,2024,Maastricht University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Health Systems Research | Clinical characterisation and management,"Health service delivery | Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P29401,838004079,Scaling up an online triage system to reduce the pressure on assistants and general practitioners.,"The pressure in primary care is increasing. For years there has been a steady increase in demand, but too few general practitioners and support such as GP assistants. We also notice this in practice (7 GPs). The COVID-19 pandemic has caused an enormous increase in the demand for care in primary care. First of all, the patient population itself: there are more concerns from patients, more psychological complaints and there is avoidance of care among a relatively large number of patients who belong to vulnerable groups. In addition, until recently there was care that was passed on from secondary care to GPs in primary care. The Dutch population now also seems to call the GP practice more quickly for low-urgency matters. GPs are overflowing and assistants are overloaded because the pressure on the telephone is high.",,2022,Maatschap Huisartsen W.G.C. Heikant,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29402,1.04303E+13,A recovery-promoting program with continuous biofeedback for optimal and personalized reintegration into work for persistent complaints after COVID-19,"There is a need for a proven effective approach for employees with persistent complaints after COVID-19. A randomized and controlled study evaluates an 18-week recovery program, consisting of: Monitoring heart rate variability (HRV monitoring) with person-oriented biofeedback Physical training based on a standardized protocol adapted to personal resilience Guidance by a physiotherapist Reintegration guidance by your own company doctor based on HRV monitoring Goal This study evaluates the extent to which this program for employees with sick leave due to persistent complaints after COVID-19 contributes to recovery and reduces fatigue. Method The effects are mapped immediately after the end of the program and 12 weeks afterwards. The process evaluation evaluates which employees and company doctors are reached and which factors contribute to successful implementation of the program.",,2023,Erasmus MC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P29403,1.04303E+13,What is the (cost) effectiveness of paramedical recovery care for people with persistent complaints after COVID-19: a comparison between two matched cohorts,"Shortly after the outbreak of the corona pandemic, the Paramedical Recovery Care scheme was started, which enabled people with persistent complaints after COVID-19 to use paramedical care reimbursed by basic insurance. The aim of this scheme was to reduce long-term complaints due to COVID-19 with the help of physio/exercise therapy, dietetics, speech therapy and/or occupational therapy. The current study shows that people who used the Paramedical Recovery Care scheme had a higher quality of life after 12 months, functioned better after 6 and 12 months, and had lower participation after 6 months compared to people who did not use it. made of this arrangement. However, the differences were small and the results should be interpreted in the context of the limitations of the current study, such as the non-randomized design.",,2023,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P29404,05160482110001,Impact of COVID-19 on the patient requiring surgery - The COVID Surg III project,"The COVID-19 pandemic has had a major impact on the care provided in hospitals. For example, regular care had to make way for care for COVID-19 patients. It is not known to what extent operations or interventions have been adjusted or postponed during the corona pandemic and what consequences this has had for patients who had to undergo an operation or intervention. Goal The aim of this project is to determine the consequences of the corona pandemic for patients with COVID-19 and for patients without COVID-19 who required surgery or intervention during this period. Method Within the COVID-Surg-III project we are bringing together the following existing, large registrations: various registrations of the Dutch Institute for Clinical Auditing (DICA) the Dutch Heart Registry (NHR) the National Registration of Orthopedic Implants (LROI) the National Intensive Care Evaluation (NICE) the appendicitis study (APPIC) the Dutch Transplant Foundation On the one hand, we analyze the consequences for patients who underwent surgery or an intervention while infected with the coronavirus. On the other hand, we evaluate to what extent the treatment of patients without corona infection has changed or postponed during the corona crisis, how this decision was made and how patients experienced this period. Finally, we ask how healthcare providers look back on the care provided and how this could possibly be improved in the future. What does this achieve? The knowledge we gain by carrying out these studies can be used in the future during any future pandemics or periods of healthcare scarcity, for example due to the increasing aging population.",,2024,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29405,05160482120001,Vulnerability and resilience of chronically ill children in relation to the covid pandemic. Joint decision-making on appropriate care for the most vulnerable young people.,"Children with chronic illness face additional challenges during the COVID-19 pandemic. We would like to know how those children are doing, and not just about their illness. Children and parents complete questionnaires about this before they come to the hospital. Purpose and method The aim of this research is to gain even more insight into: which children are doing well which children are having a hard time or are not feeling well how this relates to the corona pandemic What can we learn from children who are doing well and how can we support children who are having difficulties as best as possible? Tool for shared decision making Finally, we want to pay attention to what children themselves want to discuss with their healthcare provider. What does the child find important? Before an outpatient clinic visit, the child fills out an app (the previously developed Kindtool ) in which all domains of health are discussed. This tool encourages shared decision-making and motivates a change in behavior that is in line with what the child wants. In this project we will integrate this tool into the electronic patient file (EPD) and evaluate whether its use influences treatment choices made by paediatricians. We also investigate whether children experience more control over health-related problems by using the tool.",,2024,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29407,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 [Nivel]/Integrated Public Health Monitor - COVID-19 Phase 2 [Nivel],"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Nivel,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29409,07420112110007,"'Eat well for yourself, contact fellow sufferers through cooking workshops when eating becomes a challenge'","If you are recovering from an illness, treatment or after an ICU admission, you often experience a number of problems. The program 'Eat well for yourself: contact with fellow sufferers through cooking workshops when eating becomes a challenge' offers people the opportunity to further work on their recovery through peer meetings in the form of cooking workshops. We focus mainly on the core values ​​of the ZonMw program 'For Each Other': self-management and empowerment of people with eating problems after illness. The website www.vierkeerbeter.nl which was developed last year, offers people home help during recovery after an ICU admission (including COVID-19). The platform offers knowledge and tips to actively work on obstacles such as loss of taste and smell, muscle loss, swallowing problems, etc. Purpose: transfer to hospitals/care institutions. Contact person: Cees Smit. Email: info@smitvisch.nl",,2023,Platform Patient en Voeding,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2022 +P29410,838004063,Scaling up the use of the patient portal Huisartsenpraktijk Strikwerda & Vernooij,"General practitioner care has been under pressure for years. Since the COVID-19 pandemic, the workload has increased even more and ways are being sought to reduce that pressure. Research shows that a patient portal results in less telephone pressure, better streamlining of processes within the practice and the ability to better distribute the workload. In addition, it is known that the more patients use the patient portal, the greater this effect. The current registration percentage of the patient population in this general practice is almost 40% and not every patient actively uses the portal. The goal is to scale up the active use of the patient portal, which means that more patients will request e-consults, view their lab online and make appointments online.",,2022,Huisartsenpraktijk Strikwerda en Vernooij,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29411,08391052110003,Acute lower respiratory tract infection in primary care: improving prognosis by considering the interplay between the lung and the heart,"Acute lower respiratory infections: is there more between the lung and heart? Lower respiratory infections (LRTI), such as pneumonia, are common in adults. Some patients with LRTI require hospitalization. Observations from practice show that this mainly occurs in patients with underlying cardiovascular disease (CVD). The GP does not take this much into account, because the interplay between heart and lung is not yet sufficiently clear. We want to increase knowledge about this interplay by investigating: what are the predictors for the development of additional CVD or worsening of known CVD how additional CVD adversely affects the course of an LRTI whether blood tests of immune response say something about how an LRTI progresses with COVID-19 and without COVID-19, both in the short and long term With this research, the treatment of LRTI can be greatly improved and unknown heart disease can be detected at an early stage.",,2026,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Other,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2022 +P29412,1.04301E+13,"What is the optimal ventilation strategy in COVID-19, in particular PEEP and the moment of switch to pressure support, in invasively ventilated patients with COVID-19?","Patients with coronavirus disease 2019 (COVID-19) can develop severe pneumonia, for which they often require artificial respiration, also known as ventilation. Research into ventilation in intensive care patients in general has already led to measures aimed at preventing damage from the ventilation itself. It remains uncertain whether the same measures should be taken for COVID-19 patients. It is still unclear at what pressure it is best to ventilate, and also whether it is better to allow a patient to breathe spontaneously quickly on the ventilator. Goal The aim of this study is to determine the best pressure level for ventilation and the best time to allow a patient to breathe spontaneously during ventilation. Research design In the first and second waves of the national outbreak of COVID-19 in the Netherlands, two studies, called 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) and the 'PRactice of Adjunctive Therapies in ICU patients with COVID-19' (PRoAcT-COVID) carried out. Both studies were large, with >1000 patients in each. The data from these two studies will be combined and further supplemented to answer the questions of this new study.",,2024,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P29413,1.04301E+13,Optimal dosing and timing of steroids in hospitalized patients with COVID-19,"Patients admitted to hospital with COVID-19 often have an excessive inflammatory response. The use of the anti-inflammatory corticosteroid dexamethasone is therefore the cornerstone of the treatment of these patients. Unfortunately, there remains a group of patients who do not respond sufficiently to this treatment. Goal The aim of this study is to investigate whether patients with an insufficient response to standard anti-inflammatory treatment benefit from a higher dose, and what is the right time to administer this increased dose. Research design This project is a collaboration between a number of hospitals in the Netherlands, where there are local differences between the time of administration and dosage when it comes to steroid treatment. By merging data from a large number of patients and mapping existing practice variation and examining treatment outcomes, the researchers hope to gain more insight into the correct dosage and timing of steroid administration in the treatment of COVID-19. In addition, it will also be examined whether there are certain laboratory markers in the blood or in the lungs of the patients that predict which patients will benefit from a high dose of steroids.",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P29414,1.04301E+13,NORMO2: The effect of NOn-invasive Respiratory support on outcoMe and its risks in SARS-COV-2-related hypoxemic respiratory failure,"COVID-19 can lead to oxygen deficiency due to pneumonia. Treatment in the Intensive Care Unit (ICU) with artificial ventilation with a tube in the trachea (or invasive ventilation) is often necessary. This burdensome treatment has many disadvantages for the patient, but also for society, as the number of available ICU beds is limited. Preventing artificial ventilation and ICU admission is therefore very important. Goal To determine whether the use of less complex respiratory support can prevent tube assisted ventilation in patients with COVID-19. Research design Using databases that have collected data from thousands of COVID-19 patients during the pandemic, the researchers hope to provide clear answers to the following questions: Can artificial ventilation and ICU admission be prevented with non-invasive respiratory support (NIAO)? Examples of this are high flow oxygen administration and face mask ventilation. Is it possible to predict the success of NIAO at an early stage? Continuing NIAO for a long time and thus delaying artificial respiration can be harmful. Does NIAO have a beneficial effect for patients who no longer go to the ICU?",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P29415,1.04301E+13,Genetic Risk factors for Multi-system Inflammatory Syndrome in Children and Pediatric Long COVID (GRIP),"In rare cases, children can develop a life-threatening inflammatory disease after a corona infection. This is called MIS-C (multi-system inflammatory syndrome in children). There are also children who have long-term health complaints after a corona infection. This is called 'post-COVID complaints' or 'long COVID'. It is currently not entirely clear why some children develop serious or long-term complaints after a corona infection, while most children have few to no complaints. Objective This study investigates whether children who have had MIS-C or post-COVID complaints have hereditary abnormalities in the immune system. The researchers hope that this will help them better understand why some children become so ill after a corona infection. And if we understand this better, it can ultimately lead to new and better treatments. Study design The researchers will conduct genetic research on children who have had MIS-C and children who have post-COVID complaints. They will look at genes that are important for the immune system. They will compare this with children who did have a corona infection, but did not or hardly suffer from it.",,2025,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Post acute and long term health consequences | Disease pathogenesis,2022 +P29417,845008504,Knowledge synthesis quality of life of loved ones of people with disabilities (2019-present),"In recent years, there has been increasing attention for the quality of life of relatives and the entire family of people with a disability who require intensive care and support. Knowledge of the needs of relatives and their families is important in order to be able to support them better on this basis. In 2018-2019, Nivel, the Academic Workplace EMB, focused on people with (very) severe intellectual and multiple disabilities, and the Academic Workplace Living with an intellectual disability already conducted research into this with questionnaires and focus groups. This research is now being continued, but before we start, we want to know what research has been done in this area in the meantime - of which the COVID-19 pandemic is part. That is why we are looking for recent studies that have been carried out in the Netherlands and we are making a knowledge synthesis of them. In a final expert meeting, we will discuss the results as a stepping stone for further research into relatives.",,2023,NIVEL,,Human Populations,Unspecified,Unspecified,Unspecified,Other | Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29418,1.04301E+13,"Safe and Timely Cessation of Isolation of Patients with COVID-19, The SCIP-COVID-19 study","The duration of contagiousness of COVID-19 and therefore the duration of isolation during hospitalization is not yet known. Too early out of isolation results in infections in the hospital. Too late out of isolation is very stressful for the patient. The researchers of this study think that the isolation period can be shorter. However, there is insufficient knowledge on how to determine when someone is no longer contagious. That is why this study combines a number of characteristics that must be present or absent before you can say; ""this patient is no longer contagious"". Objective The aim of this study is to use a number of characteristics to determine when a patient is no longer contagious with a corona infection and can be released from isolation. Research design A lot of information about the patients has already been collected. This information is reused and supplemented to answer the question of this study. Expected results The results of the study are used by hospitals and announced internationally.",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2022 +P29419,1.04301E+13,Clinical features of MIS-C and COVID-19 in children,"Infection with SARS-CoV-2 can rarely lead to serious illness in children. Children with underlying conditions in particular can sometimes become seriously ill with COVID-19. In addition, you can (mostly previously healthy) children get MIS-C three to six weeks after experiencing a corona infection. MIS-C, or 'multi-system inflammatory disease in children', is a severe inflammatory response throughout the body. This happens to approximately 1 in 5,000 children who get a corona infection. It is a serious disease, for which about half of children end up in intensive care. In the Children have also died abroad. Since the start of the pandemic, pediatricians from more than 35 hospitals in the Netherlands have jointly registered data on children with MIS-C or severe COVID-19. They do this in the context of the COPP study: ""Clinical features of COVID-19 in Pediatric Patients"". The data entered is automatically analyzed daily and published on the website www.covidkids.nl shown. The information from the COPP study has proven to be very important for advice on vaccinating young children and teenagers in the Netherlands. It will remain essential in the near future to have good information about how sick children after infection with SARS-CoV-2. This is important because of the arrival of new variants, such as omikron. But also to keep track of the effect of vaccination on children occurrence of MIS-C. MIS-C cases are not kept by the GGD or the NICE registration of the hospitals. The aim of the COPP study is to expand the registration to all hospitals in the Netherlands. A complete, timely registration of children with COVID-19 or MIS-C in Dutch hospitals with 'real-time' reporting on the website is important to have continuous insight into the progress of corona infections in children in the Netherlands. We are also investigating the long-term effects of severe COVID-19 or MIS-C in children in the Netherlands.",,2024,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Clinical characterisation and management | Epidemiological studies,Disease pathogenesis | Disease surveillance & mapping,2022 +P29420,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD GHOR Netherlands / Integrated Public Health Monitor - COVID-19 Phase 2 GGD GHOR Netherlands,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD GHOR Nederland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29421,1.04302E+13,Integrated Public Health Monitor - COVID-19 Phase2 RIVM/ Integrated Public Health Monitor - COVID-19 Phase2 RIVM,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policymakers at local, regional and national level in policy formation. Based on the results, tools can be provided to set up an appropriate care and support offer, in order to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Nederland, the Nivel and ARQ National Psychotrauma Center.",,2026,Rijksinstituut voor Volksgezondheid en Milieu,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29422,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Zuid Limburg / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Zuid Limburg,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Zuid Limburg,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29423,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Gooi en Vechtstreek,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Regio Gooi en Vechtstreek,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29424,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD IJsselland/Integrated Public Health Monitor - COVID-19 Phase 2 GGD IJsselland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD IJsselland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29425,1.04302E+13,Integrated Health Research in Disasters-COVID-19 Phase 2,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Veiligheids- en Gezondheidsregio Gelderland-Midden,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29426,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Twente / Integral health research in disasters - COVID-19 Phase 2 GGD Twente,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Twente,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29427,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Hollands Noorden,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29428,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Brabant-Zuidoost / Integrated health research in disasters - COVID-19 Phase 2 GGD Brabant-Zuidoost,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Brabant-Zuidoost,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29429,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Flevoland / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Flevoland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Flevoland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29430,1.04302E+13,Integral health research in disasters - COVID-19 Phase 2 GGD Drenthe,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Drenthe,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29431,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Hart voor Brabant / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Hart voor Brabant,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Hart voor Brabant,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29432,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 Municipality of Utrecht Public Health / Integrated Public Health Monitor - COVID-19 Phase 2 Municipality of Utrecht Public Health,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Gemeente Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29433,1.04302E+13,phase 2 integrated health monitor GOR-COVID-19,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD West-Brabant,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29434,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 - GGD North and East Gelderland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Noord- en Oost-Gelderland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29435,1.04302E+13,Integrated Health Research in Disasters (GOR) COVID-19 phase 2,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Amsterdam,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts | Social impacts,2022 +P29436,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 Municipality of Rotterdam/GGD Rotterdam-Rijnmond,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Gemeente Rotterdam,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29437,1.04302E+13,"Corona Health Monitors Youth part 2, young adults, Adults & Elderly and Public Mental Health Care 2022-2025 in the context of GOR COVID-19 sub-program","Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Zuid Holland Zuid,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Vulnerable populations unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29438,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Gelderland-Zuid / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Gelderland-Zuid,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Gelderland-Zuid,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29439,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD regio Utrecht,,Unspecified,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29440,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Kennemerland / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Kennemerland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Kennemerland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29441,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Fryslân / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Fryslân,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Fryslan,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29442,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Groningen,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29443,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Zaanstreek-Waterland / Integrated Public Health Monitor - COVID-19 Phase 2 GGD Zaanstreek-Waterland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Zaanstreek-Waterland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29444,1.04302E+13,Integrated Public Health Monitor - COVID-19 Phase 2 GGD Limburg-Noord,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Limburg-Noord,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29445,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Hollands Midden,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,Hecht GGD Hollands Midden,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29446,1.04302E+13,Integrated Public Health Monitor - COVID-19 Phase 2 -GGD Haaglanden,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Haaglanden,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29447,1.04302E+13,Integrated Health Research in Disasters - COVID-19 Phase 2 GGD Zeeland / Integral health research in disasters - COVID-19 Phase 2 GGD Zeeland,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,GGD Zeeland,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29448,1.04302E+13,Integrated Public Health Monitor - COVID-19 Phase 2 - ARQ National Psychotrauma Centre: WP5,"Integrated Health Monitor GOR COVID-19 2021-2025 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis with the Integrated Health Monitor GOR COVID-19 2021-2025. This monitor consists of various sub-studies aimed at youth, young people, adults, the elderly and extra vulnerable people. Insight is provided into the impact of corona on the health and well-being of the Dutch population. The aim of the monitor is to advise and support policy makers at local, regional and national level in policy making. Based on the results, tools can be provided to set up an appropriate care and support offering to limit the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs in collaboration with GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2026,ARQ Nationaal Psychotrauma Centrum,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P29449,1.03201E+13,At home in working from home: A guideline for responsible embedding of working from home in reintegration programs in the event of absenteeism,"Question In reintegration programs in the event of absenteeism, returning to the physical workplace is central to maintaining ties with work and minimizing the barrier to resuming work. Until now, working from home has not been seen, or widely applied, as a potentially effective tool for reintegration. Due to the COVID-19 pandemic, the facilities are in order to make working from home possible in different work contexts. This creates momentum to evaluate the value of working from home in reintegration. How can working from home be responsibly embedded in reintegration programs in the event of absenteeism, so that it facilitates an early return to work? Research In co-creation with employees, managers, company doctors and labor experts, a draft guideline is being developed for the application of working from home in reintegration processes. After this, the influence of embedding working from home in reintegration processes will be investigated within two organizations (Radboud University and UWV) in three work contexts (screen work, education, client contact). The influence on the recovery course and return to work, bonding with work and motivation and the experience of the reintegration process by employees, managers, company doctors and labor experts are examined. Based on this, a definitive evidence-based home work guide and user training will be developed. Result The aim of this project is to develop, together with practice stakeholders, a working from home guideline that enables managers, employees, company doctors and labor experts to systematically consider whether, when, for whom and under what circumstances working from home can contribute to a responsible return to work. Dissemination and implementation The guidance and training are integrated into an educational module of the company doctor training (via project partner SGBO, RadboudUMC). In addition, a symposium is being organized for company doctors, HR professionals and labor experts. The products, including educational videos, are offered via the project website and websites of the parties involved. Professional publications and open access scientific publications are also developed. Organizations involved Radboud University, Amsterdam UMC, Further training to become a company doctor (SGBO), UWV, Arbo Unie BV, Dutch Association for Occupational and Occupational Medicine (NVAB), Dutch Association for Occupational Health and Safety Experts (NVvA)",,2025,Radboud Universiteit Nijmegen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other | Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P29450,1.043E+13,Impact of the COVID-19 pandemic on patients with inflammatory rheumatic disease,"In collaboration with the Target To B! consortium and Sanquin, we investigated the extent to which patients with immune-mediated inflammatory diseases (IMIDs) who are treated with immunosuppressive drugs after corona vaccination are protected against experiencing (severe) corona infections. This is relevant because certain immunosuppressive medications negatively affect the production of protective defenses in the body. We collected data from 4192 vaccinated patients with IMIDs and 822 vaccinated healthy control participants. Our results show that most patients with IMIDs do not become more or more seriously ill from corona infections after vaccination compared to healthy control participants. Only patients treated with B-cell therapy are at greater risk of becoming seriously ill from a corona infection after vaccination. Our results therefore show that patients with non-immune-mediated diseases do not necessarily have to be seen as a risk group for a serious course of COVID-19, but that caution when prescribing B-cell therapy to patients remains important.",,2022,Reade Research BV,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity,2021 +P29451,1.04301E+13,COVID19 Outcomes in Older People - the COOP study,"More than 90% of all deaths from COVID-19 occur in patients aged 70 years and older and functional decline is common. The elderly are very different in terms of vitality and vulnerability. Goal Customized treatment starts with a good assessment of the prognosis and knowledge about the disease, but much is still unknown. Does frailty predict the short- and long-term consequences of COVID-19 in older people? How do biological aging and vulnerability play a role in mortality or recovery? What are goals that are important for older people when making treatment decisions for acute serious conditions? Research design In the COOP study, all necessary professionals and elderly people work together to optimize the consequences of elderly people with COVID-19 through thorough scientific research. By using the many Dutch data previously collected in elderly people with COVID-19 in primary care, at home, in hospitals and in nursing homes, the results will become available quickly.",,2024,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Prognostic factors for disease severity,2021 +P29452,838002944,Scaling up an online triage system to reduce the pressure on assistants and general practitioners.,"The pressure in general practitioner care is increasing. There has been a steady increase in demand for years, but too few GPs and support such as GP assistants. We also notice this in practice (7 general practitioners). The COVID-19 pandemic has caused a huge increase in healthcare demand in primary care. First of all, our own patient population: there are more patient concerns, more psychological complaints and there is avoidance of care in a relatively large number of patients who belong to vulnerable groups. In addition, until recently, care was passed on from secondary care to primary care physicians. Nowadays, the Dutch population also seems to be more likely to call their GP practice for low-urgent matters. General practitioners are overflowing and assistants are overloaded because the pressure on the telephone is high. Moreover, people sometimes demand care that is not reasonably necessary.",,2022,Maatschap Huisartsen W.G.C. Heikant,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29453,838002929,"Scaling up project of first-line multidisciplinary rehabilitation as well as maintenance of resilience at a distance for vulnerable elderly people living at home, with or without a chronic condition","Remote care is an effective treatment method for vulnerable elderly people and for people who have undergone surgery and an option to continue to follow a program frequently. This also applies if home treatment is temporarily not possible due to COVID-19. Together with partners from (para)medical healthcare and programs aimed at care, Manual-Fysiocare has developed a multidisciplinary online rehabilitation program: physiotherapy/occupational therapy, psychology and dietics tailored to your needs and can be carried out remotely. To overcome the limited knowledge of digital resources, Manual-Fysiocare also wants to support this, because care must always be possible, even when treatment at home is not possible. To ensure that the treatment is safe, a caregiver or informal caregiver is present during the initial phase and during the physiotherapy exercises. In the short term, we want to develop e-learning and communication material about the software and the program for greater support and a greater reach.",,2022,Fysiotherapie Daphne Bos,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers | Health Personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29454,838002917,The combination of online sessions and telemonitoring using a questionnaire regarding shoulder complaints.,"While before COVID patients often came to our location, we have increasingly worked online in the past year. Using the EPD, which has a patient portal, we can easily set up questionnaires related to the patient's capacity and functionality. We have also created a basic program in Physitrack (also linked to our EPD Intramed) to set up an exercise program. The combination of online sessions, telemonitoring through a questionnaire regarding shoulder complaints such as the DASH or SPADI can easily be set up in this way. In addition, remote consultations can be achieved safely and easily with the Physitrack program. The exercise program ensures good therapy compliance with reminders.",,2022,Manuele en Fysiotherapie Andeweg,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29456,1.04302E+13,GOR-COVID-19 Youth Health Monitor 2021 - GGD Hollands Midden,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Hollands Midden,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29457,1.04303E+13,VeCosCO:Neurobiological basis of long-term cognitive complaints and fatigue after COVID-19,"Long-term fatigue and cognitive complaints are common problems after a SARS-CoV-2 infection. These complaints have a major impact on daily life. So far, little is known about the course and treatment options. Goal The first goal of this research is to map the long-term fatigue and cognitive complaints of people after experiencing SARS-CoV-2. The second goal is to use imaging techniques (the PET scan and the MRI scan) to gain insight into any underlying pathophysiological processes in these long-term complaints. Background By obtaining more information about the course of long-term fatigue and cognitive complaints, care for people with these complaints can be improved. There are also strong indications that the presence of inflammatory cells in the brain plays a role in long-term fatigue and cognitive complaints. By investigating this further, new insights may be gained for possible treatments. Research design People with long-term fatigue and cognitive complaints are initially mainly recruited from existing SARS-CoV-2 research cohorts. They are extensively investigated and prosecuted in due course. In addition, additional imaging tests are performed on some of these people (the so-called TSPO PET scan with which we look at inflammatory cells in the brain and functional MRI).",,2024,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P29458,1.04303E+13,"Persistent complaints after COVID-19 infection: epidemiology, pathophysiology, prediction, and communication, the CORona Follow Up (CORFU) study","Project CORona Follow Up (CORFU) investigated persistent complaints after COVID-19 infection. CORFU bundles 6 national COVID-19 cohorts and 1 survey. The goals were to map post-COVID symptoms and their relationship with quality of life (QoL), develop a prediction model and investigate pathogenesis. At 24 months, 43% of participants with an infection at home, 65% of ward patients and 63% of intensive care patients, had post-COVID symptoms. Fatigue was most common. QoL did not differ between the Covid-19 patients, but it is lower than in people without previous COVID-19. Having at least one post-COVID symptom two years after infection can be predicted by gender, severity of initial infection, and other health conditions that existed before getting COVID-19. The results highlight the need for research into the underlying mechanisms and treatment options for patients with post-COVID symptoms.",,2023,Maastricht University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences,2021 +P29459,1.04303E+13,Insight into persistent complaints after Covid-19 infection: a mixed methods approach.,"Some people who have experienced a corona infection continue or develop complaints in the longer term. This is called Long COVID and little is known about it yet. In this study, the researchers focus on underlying causes and risk factors for Long COVID and map out the care pathways and the nature, severity and duration of the persistent complaints. They pay extra attention to various vulnerable groups in our society. Goal The research into Long COVID contributes to a better characterization and interpretation of Long COVID complaints: • Focus on providing more insight into the nature, severity and duration of the complaints; • Investigate risk factors and clues to possible underlying causes; • Mapping the 'care pathways' of patients with Long COVID and providing advice on possible improvements. Background The researchers use 3 different cohorts: The EPD cohort with irreducibly linked data from: i. electronic patient records (EPDs) from general practices and general practitioner posts (Nivel First Line Healthcare Registries and academic GP networks (Maastricht, Radboud and Groningen) ii. the hospital registrations (National Basic Register of Hospital Care, LBZ) iii. socio-economic and demographic data from Statistics Netherlands. These 3 databases are linked at individual patient level, are nationally representative and cover 10% of the Dutch population. A distinction is made between people with persistent COVID complaints (~14,000 people) and, among other things, a control group of people with COVID infection, but without persistent complaints (~126,000 people); The Nivel Corona cohort: from more than 400 corona patients, in addition to data from EPDs, we also collect data from questionnaires about their quality of life and how they experience their complaints and care. The questionnaires are administered immediately after infection and after 3, 6 and 12 months; Interviews: 16-20 patients, including patients with low health literacy, and 8-10 general practitioners are interviewed to identify specific points of interest in vulnerable patient groups. Research design Quantitative and qualitative research methods are combined within the research. For example, existing data from electronic patient files from general practitioners and hospitals are combined and analyzed and data is collected and analyzed through questionnaires and interviews. (First) Results The results offer healthcare providers and patients starting points for better support and early recognition of patients with persistent COVID-19 complaints. Results are distributed nationally and internationally through various platforms and organizations. A patient panel and advisory committee with representatives of relevant stakeholders advise the project. The project group shared a news report and article about their insights regarding the number of individuals with post-COVID syndrome. Here you will find the news item and here the scientific article . Executive parties The project is a collaboration between Nivel, UMCG, Radboud UMC, MUMC and Dutch Hospital Data.",,2024,Nivel,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P29460,1.04301E+13,DEFENCE: Determination and Evaluation of the Frequency and Effects of myocardial damage iN patients with a SARS-CoV-2 infEction,"It is currently largely unknown to what extent the heart is involved in COVID-19. Goal The aim of this project, funded by ZonMw, is to determine the occurrence and consequences of heart damage in patients who have experienced COVID-19. Research design Within DEFENCE, several large existing cohorts are brought together: from healthy top athletes and patients in the general population who have recovered from the infection at home to seriously ill patients who have been in hospital. Various tests are performed to detect heart damage, including an MRI scan of the heart. Patients will also receive questionnaires to unravel whether certain complaints, such as palpitations and chest pain in the period after COVID-19, are related to heart damage. By linking the data within this project with external data sources, it will be investigated whether patients after COVID-19 have an increased risk of cardiac complications in the short and long term.",,2024,Dutch CardioVascular Alliance,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2021 +P29461,1.04301E+13,General practice Research Infrastructure Pandemic Preparedness Program (GRIP3),"The COVID-19 pandemic has had major consequences for the Dutch population. General practitioners saw many patients with acute complaints due to COVID-19, but it is currently unclear which early drug treatments prevent a complicated disease course. In this proposal, the eight Dutch departments of general medicine and Nivel join forces from the General Practice Research Consortium. In close consultation with patient representatives and other stakeholders, they are developing three studies (work packages) regarding COVID-19 care by general practitioner care. In addition, the Consortium will also conduct research aimed at improving the facilities and preconditions for carrying out general practice research. Goal The aim of the 3 work packages focused on COVID-19 is to provide better scientific substantiation for the home treatment of COVID-19 by general practitioner care. The aim of the modules in the fourth 'infrastructure' work package is to support general practitioners and patients to participate in clinical and scientific research in order to also collect reliable data about treatments outside the hospital, to make it easier for general practitioners and patients. to participate in scientific research and to provide reliable research data more quickly in the event of future pandemics. Background During the beginning of the pandemic, due to the acute situation and unfamiliarity with treatment options, care for COVID-19 patients mainly took place in the hospital and was mainly referred from primary care in case of serious complaints. As more became known about treatment options, these were also increasingly applied by general practitioners to positively influence the course of the infection to prevent hospital admission. Facilities to investigate the effects of treatments and the course of the disease are necessary. There are also opportunities in the field of remote care and the application of more complex care in the home situation. Research is important to clarify and transfer the preconditions for contributing to safe and high-quality care at home. Research design In work package 1, the consortium uses nine large registration databases of routine care data from general practices to look at 1) the treatments used with medicines prescribed by general practitioners during the first COVID-19 waves in the Netherlands and 2) how often long COVID (long-term complaints after a COVID-19 infection) and which processes these patients go through with which results. In a national study in which a group of patients who receive a promising medicine is compared with a group of patients who do not receive the drug, the PRINCIPLE-NL trial is in line with a British study into the effect of promising medicines on the course of COVID-19 infection in risk groups (work package 2) in general practitioner care. The Covidtherapy@home study (work package 3) investigates whether home treatment tailored to the patient with oxygen support, anti-inflammatory dexamethasone and blood thinners is equivalent and safe for seriously ill COVID-19 patients compared to hospital admission. In addition to these COVID-19 work packages, the General Practice Research Consortium will set up several processes to significantly improve the infrastructure for general practice research in the Netherlands. The 3 work packages will be carried out in the first two years of the project. The next two years will be devoted to consolidating the infrastructure. Executive parties General Practice Consortium University Medical Center Groningen, Maastricht University, Leiden University Medical Center, Radboudumc, University Medical Center Utrecht, Amsterdam UMC - location AMC, Amsterdam UMC - location VUmc, Erasmus MC and Nivel. Collaboration partners ExpertDoc, ZorgDomein, Dutch Society of General Practitioners, C-support, Zorgbelang Inclusief, Institute for Responsible Use of Medicines, Personal Health Train",,2025,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P29462,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-program - GGD Gooi en Vechtstreek,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,Regio Gooi en Vechtstreek,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29463,1.04303E+13,"Persistent Complaints after COVID-19: perspectives from the population, patient, and care","Some people who have had a corona infection continue or develop physical, psychological or cognitive complaints; this is called long COVID or persistent complaints after a COVID infection. It is unclear what the causes and consequences of these complaints are for the person and society and how healthcare can provide an answer to them. This research contributes to the development of a care pathway for patients with long COVID. Goal The objective of this research is to generate practically applicable knowledge for improving care for patients with long COVID. The researchers will contribute to the development of a care pathway for patients with persistent complaints after COVID-19. Background Current studies into long COVID do not take into account complaints that were already present before the infection and are largely based on clinical cohorts, while a large proportion of people with long COVID have not been hospitalized. This research is therefore an addition to current research into long COVID. Research design The researchers of this project first map out how often long COVID occurs, what symptoms it involves, and what personal and social consequences it has. To gain more insight into the underlying mechanisms, the researchers are conducting extensive measurements in Lifelines participants with long COVID. Lifelines is a cohort study and biobank in the Netherlands that collects all kinds of data about health and body materials. The current study looks for evidence of organ damage and immunological or metabolic dysregulations in participants with long COVID. The researchers in Lifelines also look at who is at risk of developing long COVID. In addition, patients with long COVID will be interviewed to map their experiences with long COVID and care. All these results come together in an action research, in which healthcare providers will improve care for long COVID together with patients. Executive parties This research is carried out in collaboration with regional general practitioners, paramedics and doctors in secondary and tertiary care by the University Medical Center Groningen, the Radboud University Medical Center and the Lungfonds.",,2023,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management | Health Systems Research,Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Health service delivery,2021 +P29464,1.04301E+13,TURN-COVID: Dutch cohort study evaluating the use of neutralizing monoclonal SARS-CoV-2 antibodies,"Despite vaccination, some patients with a compromised immune system have an increased risk of Covid-19 with a serious course. The use of neutralizing monoclonal SARS-CoV-2 antibodies is a breakthrough in the treatment of Covid-19 for this patient group. This new therapy prevents Covid-19 related hospitalizations and deaths, provided the drug is given early in the disease process. This could substantially reduce the pressure on hospitals. Goal TURN-COVID is a national cohort study focused on the use of neutralizing monoclonal SARS-CoV-2 antibodies as therapy against Covid-19 in high-risk patients. The aim of the study is to map the use, effectiveness, safety and costs of the different antibodies. In addition, a national platform is being created to evaluate future unregistered treatments for Covid-19.",,2025,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Therapeutics research, development and implementation",,2021 +P29465,1.04301E+13,CoLab-score and viability PCR for SARS-CoV-2: routine blood test algorithm proven by elimination of viable SARS-CoV-2 to identify patients in order to facilitate discharge and/or de-isolation,"Long-term occupancy of isolation rooms by COVID-19 patients leads to further pressure on regular non-COVID care. In addition, treating and caring for COVID-19 patients in isolation is associated with physical and psychological burden for the patient and healthcare staff. An algorithm has been developed that can calculate the so-called CoLab score based on the patient's age and about 10 standard blood values ​​that are measured daily in the ICU. The researchers of this study want to investigate whether the CoLab score can be used to release COVID-19 patients from isolation earlier and safely. Research design The CoLab score will be compared with the current standard PCR test and a recently developed PCR test (viability PCR) that can exclude the presence of infectious virus particles. In this way, the researchers can demonstrate that a patient with a normalized CoLab score is no longer contagious and can be safely removed from isolation.",,2024,Zuyderland Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2021 +P29466,1.04301E+13,COVID-CLIMATE: COVID-19: The role of CLinical and IMAging TEsts,"In the early days of the pandemic, patients were treated with oxygen or ventilation. Medications were also tried with varying results. Some medications have proven to be effective, but it is still unclear to whom these medications are best given. During this period, many CT scans were made to make the diagnosis, because there were few PCR tests. However, these scans also provide information about the severity of the disease and possibly its progression. This project investigates whether the scans can be used to predict better who will need the medicines. Goal Determine whether CT scans can be used to predict which COVID-19 patients will need medication. Research design Some patients continue to have complaints after recovery. The researchers try to predict for each person how this will proceed. To do this, they use CT scans and other information about the health of former patients. In some patients they will make a new type of scan a few months after recovery. This allows them to see whether the permanent abnormalities are caused by inflammation or early scarring.",,2023,Maastricht University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2021 +P29467,1.043E+13,"COVID-19, Food Security and Economic Diversity in Curaçao, Aruba and Sint Maarten","Food security in small island communities primarily dependent on tourism is problematic. The small land area and high population density combined with the pressure of tourism make it impossible to meet the full food needs with a conventional approach. Dependence on external food producers is inevitable for continuity of high-quality food supply. Partly meeting food needs is possible through local food production. Its development also contributes to the necessary diversification of the economy. This project examines the effect of the COVID-19 pandemic by asking local stakeholders about food production and availability, economic impact and employment in the sector as well as nutritional practices. Analysis of the collected data provides a picture of the resilience of the food chain and the associated potential for economic diversification.",,2024,Universiteit van Curaçao,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts | Other secondary impacts,2021 +P29468,1.04301E+13,"Sniffing out Covid: Perspective for patients with persisting loss of smell, towards better understanding and treatment.","In the past year, an estimated 2 out of 3 patients with a COVID-19 infection experienced loss of smell. For the majority, the sense of smell returns within a few weeks, but there are also patients whose complaints persist or who experience a disturbed sense of smell. These complaints have a major impact on daily life. In addition, not enough is known so far about the course and treatment options of loss of smell in COVID-19 patients. This study therefore investigates the natural course of anosmia (lack of sense of smell) in the context of COVID-19 and whether this can be beneficially influenced with (local) corticosteroids. Goal The aim of this study is to investigate the natural course of anosmia (lack of sense of smell) after a COVID-19 infection and whether this can be beneficially influenced with (local) corticosteroids. Research design Over the course of a year, the sense of smell and taste of a group of COVID-19 patients will be repeatedly measured and their influence on eating behavior and quality of life examined. The researchers are also investigating the effect of a change in smell on the brain. They are also conducting research into treatment options for loss of smell in COVID-19, with oral corticosteroids. With this they want to improve the care and prospects for this patient group and gain more knowledge about effective treatments.",,2025,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis | Prophylactic use of treatments,2021 +P29469,1.04301E+13,Long-COVID and vaccination in RECoVERED,"After having a SARS-CoV-2 virus infection, a significant proportion of people continue to have symptoms, so-called 'long COVID'. The cause of these long-term symptoms is still unclear, but could be related to a disrupted immune system. This has led to the idea that vaccinating people with symptoms of long COVID could alleviate these symptoms by putting the disrupted immune system back on track. This project will investigate whether this is indeed the case. Objective To investigate whether 'long COVID' symptoms could be related to a disrupted immune system and the effect of vaccination on this. Background After having a SARS-CoV-2 virus infection, a significant proportion of people continue to have symptoms. This is called long COVID if the symptoms persist for more than 3 months. Long COVID places a significant burden on individual well-being and quality of life. It is also expected to have major economic consequences due to health-related costs and reduced work capacity. It is currently unclear what the cause of these long-term symptoms is. The symptoms may be the result of residual virus particles leading to a chronic inflammatory response, or of an abnormal immune response in which antibodies are produced that react to the body's own tissue. Vaccinating people with long-COVID could put the disrupted immune system back on track. It is therefore important to gain more insight into the development of long-COVID and the effect of vaccination on this. This is important for the vaccination policy, and perhaps also other interventions to prevent or treat long-COVID. Study design The study is being conducted in a large group of COVID-19 patients who have already been followed for a long time in an ongoing cohort study (RECoVERED). Of the study participants, 175 people were vaccinated, half of whom had long-COVID symptoms at the time of vaccination. In this group, the properties of the immune response are being examined in detail in relation to the nature and duration of long-COVID symptoms. It is also being investigated whether and what influence vaccination has on this. Executing parties Amsterdam UMC and GGD Amsterdam.",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Vaccines research, development and implementation",Disease pathogenesis | Post acute and long term health consequences | Characterisation of vaccine-induced immunity,2021 +P29470,1.01E+13,Stimulation of e-health within the Regional Plan for Integrated Care Heerenveen and surrounding areas.,"Due to COVID, digitalization has accelerated in the Heerenveen region and surrounding areas in recent years. In the past period, efforts have been made to achieve the following objectives: Better implement quickly developed initiatives so that they are not temporary adjustments, but become structural changes. Make digitalization more of a regional theme so that we learn more from each other and achieve acceleration. In recent years, the use of digital resources in the Heerenveen region has mainly been a theme within organizations, and to a lesser extent between organizations. The faster, simpler and digital exchange of information and knowledge ensures the desired/necessary shift in care. During the project, efforts were made to improve the implementation of the consultations. All departments now offer the consultations. In addition, a dashboard has been developed that shows what percentage of patients are still referred to the same specialty for the same condition after a consultation consultation. The referrals take place via the healthcare domain and there is a link between the healthcare domain and the hospital's EPD.",,2022,Ziekenhuis de Tjongerschans,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Health Systems Research,Health service delivery | Health information systems,2021 +P29471,838002847,Online information meetings for patients at the Levinas health center,"Levinas 'care for well-being' is a health center in the Kralingen area in Rotterdam and houses two general practices, a pharmacy, a number of physiotherapists, a group practice for obstetrics, a dietician, spiritual counselor, speech therapist, medical pedicure, podiatrist, psychologist and an establishment of Star SHL. As a result of the COVID-19 pandemic, it is no longer possible to physically provide our patient population with information about the condition or disease individually or in groups. We expect that this will not be possible in the near future as we did before the corona crisis. This forces us to look for new options for advice and generic information provision remotely to our clients. This is not about regular care for individual patients, but about preventive information meetings about, for example, diabetes, COPD, psychosocial care (stress and anxiety, SOLK) or spiritual care.",,2021,Stichting Gezondheidscentrum Levinas,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29472,1.04301E+13,Vaccinating children with Long-COVID to improve overall fitness (VINCERE),"Not only adults but also many children suffer from long-term complaints after experiencing a COVID-19 infection, such as fatigue and shortness of breath. If these complaints persist for weeks to months, we call it long COVID. Initial reports from adult patients with long COVID show that a vaccination against the coronavirus can improve symptoms. The aim of this study is to evaluate whether this effect also exists in children. Goal Investigate the effect of COVID-19 vaccination in children with long COVID between the ages of 12 and 18. In addition, the differences and similarities in the pattern of complaints and the risk factors for the development of long COVID in children in different age groups are examined. Background Some adults who experience COVID-19 have persistent complaints, called long COVID. These complaints can last for weeks to months. It is unclear what the exact cause of the complaints is, but there are probably several causes. Long COVID can also occur in children, both after severe and mild acute COVID-19 infections. While it appears that some adult patients experience a decrease in long COVID complaints after vaccination, nothing is yet known about a possible positive effect of COVID-19 vaccination in children. Given the impact of this disease on individual functioning and society, it is important that there is more insight into the pathophysiology and possible treatment of long COVID in children. Research design This study examines the effect of a vaccination on fatigue complaints in children aged 12-18 years old who experience complaints for more than 12 weeks. It is examined whether there are differences between children in which the complaints do and do not improve. Because only the Pfizer-BioNTech mRNA vaccine is currently approved for children aged 12 and over, it will be used in the study. The fatigue complaints are analyzed before and after vaccination. In addition to looking at the effect of vaccination, children aged 12-18 years are compared with children aged 6-12 years with long COVID who have not yet been vaccinated to map the pattern of complaints. Executive parties Spaarne Gasthuis, Emma Children's Hospital and Amsterdam UMC.",,2023,Spaarne Gasthuis,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Vaccines research, development and implementation",Post acute and long term health consequences | Adverse events associated with immunization,2021 +P29473,1.04301E+13,Timing and sequence of vaccination against COVID-19 and Influenza (TACTIC),"Background and purpose It is currently uncertain how long the corona vaccinations protect against COVID-19. It may be necessary to give vulnerable people an annual booster of the corona vaccine before the winter season to provide them with lasting protection against COVID-19. Then there is also the annual flu shot, but it is unknown whether and how these vaccines influence each other. This study focuses on assessing the immune response and side effects after combined vaccination against COVID-19 and influenza in people ≥ 60 years of age. Research design In this study, 140 subjects aged ≥ 60 years receive a flu vaccine and corona vaccine at different times and sequences. Their blood is examined to see how their immune system responds to these vaccinations. Participants also keep track of how much they suffer from side effects. Expected results The researchers expect to provide a good picture of how corona and flu vaccinations can be given as efficiently, effectively and safely as possible.",,2023,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,Mpox,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P29474,838002864,Implementing home measurements (ECGs) via the BeterDichtbij app at the Cardiology department,"This project is made possible by: ZonMw. The COVID pandemic has led to new ways of communicating with patients. There is also an increasing need for providing care 'remotely'. The hospital started the technical rollout of the BeterDichtbij service in 2020 (for both messages/conversations and video calling via the app). Providing this form of care has added value for both healthcare provider and patient. This makes it possible to explore possibilities for communication and results of measurements (which the patient carries out himself in the home situation) via BeterDichtbij. This means that the patient has to come to the hospital less frequently for a physical appointment and the patient can collect measurements in his own home situation. The care provider can assess these measurements at a suitable time and, if necessary, can easily communicate with the patient via BeterDichtbij.",,2021,Spijkenisse Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +P29475,1.04301E+13,"Switching of COVID-19 vaccines: A solution for the problems? A multicentre, randomised, single blind, controlled trial among HealthCare Workers (HCW) vaccinated with Janssen: the SWITCH trial.","Combining COVID-19 vaccinations could accelerate vaccination campaigns in the future and reduce the impact of supply problems. It could also theoretically elicit a higher (more antibodies) and a broader (against more variants) immune response. Several studies have already been started in Europe to investigate the safety and immune response in combination with AstraZeneca. In consultation with these international studies, the SWITCH study was set up in the Netherlands. This study focuses on administering a second corona vaccination to hospital employees who have previously been vaccinated with Janssen. Objective This study investigates the effect of a second homologous or heterologous corona vaccination after a first Janssen vaccination. In addition, the occurrence of side effects with homologous and heterologous booster vaccination is examined. Study design In this study, employees who have been vaccinated with Janssen will be vaccinated a second time with the Janssen, Pfizer or Moderna vaccine. Participants will be randomly assigned to one of the following groups: 1. No additional vaccination; 2. A second dose with Janssen; 3. A second dose with Pfizer; 4. A second dose with Moderna. Blood is taken at 4 different times: day 0 (before 2nd vaccination), day 28 (primary endpoint), after 6 and 12 months. First results The first results of the SWITCH study have been made public. This publication is a pre-print where peer review is still taking place. The results show that different combinations of booster vaccinations are well tolerated in healthy people and show a clear response. Administering a booster vaccination with an mRNA vaccine (Moderna or Pfizer) after a Janssen vaccination shows a higher response compared to administering 1 or 2 Janssen vaccinations. On January 19, 2022, new results were published in the New England Journal of Medicine .",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine design and administration | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P29476,838002828,Scaling up and expanding Right Care in the Right Place - immunoglobulins,"Establishment of the care pathway for immunoglobulin treatment in the home environment by Alcura. Due to JZOJP, reinforced by COVID, chronic medication treatments are increasingly given at home instead of in the hospital. This offers more comfort and quality for the patient. In collaboration with hospitals, Alcura has years of experience in supplying and administering specialist medication at home. This was often low-complex medication, for which a nurse provided administration or instructions. Highly complex care pathways, such as immunoglobulins, require new services, including infusion care, including infusion pumps and guidance of patients from infusion to subcutaneous administration. By motivating and training patients to administer their own medication, we promote self-management and the patient becomes independent of nursing care, so that Alcura can help other patients who need it. In this way we combine efficiency with personalized care.",,2021,Alcura apotheek,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Indirect health impacts",2021 +P29477,838002779,Charley Toorop Health Center implementation of e-health solutions,"Charley Toorop Health Center houses a team of general practitioners, center assistants, practice assistants and a nurse specialist who provide care to the patient population in the Rotterdam Prins Alexander area. The health center also offers physiotherapy, obstetrics, dietetics, podiatry and mental health care and has a pharmacy. Due to the growth and certainly also due to the restrictions imposed on us by the COVID-19 pandemic, we want to accelerate a number of important steps in further digitalizing our organization and structurally implementing e-health solutions. This is not only necessary to further optimize mutual coordination and internal collaboration, but also because our patients are increasingly asking for online contact. We have realized that we are insufficiently able, due to a lack of time and expertise, to take the necessary steps that are now required. The coach will help us with this.",,2021,Gezondheidscentrum Charley Toorop,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29478,1.04301E+13,Thrombosis with Thrombocytopenia Syndrome after SARS-CoV-2 vaccination,"Thrombosis in combination with a low platelet count occurs in rare cases after vaccination with the COVID-19 vaccines from AstraZeneca and Janssen. Most of these patients developed a thrombosis in the head (sinus thrombosis). The disease is called vaccine-induced immune thrombotic thrombocytopenia (VITT). There are many unanswered questions about VITT, including: 1. How common is VITT? 2. What are the clinical manifestations and prognosis of VITT? 3. Has the prognosis improved after the introduction of international treatment guidelines? 4. How common are PF4 antibodies (the suspected cause of VITT) in healthy people who are vaccinated? 5. What role do the clotting and immune systems play in VITT? The purpose of this research is to answer these questions. We provide doctors and policy makers with scientific evidence that can be used to optimize vaccination strategies and the treatment of patients with VITT.",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Vaccines research, development and implementation","Supportive care, processes of care and management | Adverse events associated with immunization",2021 +P29479,1.01E+13,"Care for hearing-impaired children and young people in the Northern Netherlands (Groningen, Friesland, Drenthe)","Bureau HHM has created a regional picture of children and young people with hearing problems in the Northern Netherlands. By means of a digital questionnaire, information was collected from healthcare providers, parents and other relevant stakeholders about this target group in the region, the care provided to this target group, including bottlenecks and gaps, cooperation between parties, systemic working and the influence of Covid-19. 19. The results of this questionnaire were discussed during a regional meeting. Some bottlenecks that have emerged are the small target group and finding staff. A number of gaps indicated by parties, such as specific care provision for children with hearing problems and an intellectual disability. The regional meeting showed that this specific care offering is sometimes available, but that it is apparently not well received. Even better cooperation between parties can improve these bottlenecks and gaps.",,2022,GGMD,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2021 +P29480,1.04302E+13,"Convalescent Antibody-Mediated Treatment of COVID-19 Infections in Patients with B-cell dysfunction, a Randomized Trial - COVID-Compromise Study",Not available,,2025,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Clinical trials for disease management,2021 +P29481,7430085090,Young & More Wageningen,"In Wageningen, 11 groups of young people participated in Perspective for Youth. They attended workshops in which they thought about how they wanted to contribute to Wageningen society. The guidance provided by Thuis Wageningen and Change Makers Wageningen was tailor-made: each group looked at what was needed. An International Transition Class brightened up a schoolyard with homemade birdhouses, a group of students cooked for the elderly, a European Football Championship for children was organised, money was raised for the fight against Covid in India, and attention was drawn to setting boundaries regarding sexuality. Participants found it very valuable to do something for others and to organize it all themselves. They have learned to plan, work together and make new contacts. And they learned a lot about their talents and what they liked. An organizer of the Kids European Championships: 'It's great to see the children so happy and enthusiastic. Instructive about what you need to prepare.'",,2021,Gemeente Wageningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,,,2021 +P29482,7430085101,Youth team goes CVD,"Young people from the municipality of Edam-Volendam, in collaboration with each other and professional parties, organized various activities and/or contributed to the supervision of activities. From ""corona-proof"" sports tournaments, to pool games and from gaming and ""stuntman"" workshops, to organized discussions and debates. Invent, prepare (and announce/communicate) and implement activities yourself. At a time when the sentiment of ""being powerless due to the Covid rules"" became stronger, the young people involved gained influence in the range of activities in their own area and even involved adult volunteers. The enthusiasm of the participants caused experienced professionals to look at the range of activities with renewed energy and more connections between young people after the summer holidays. This is noticeable in the debates/conversations that are held among themselves about next steps, but also in the composition of groups that visit each other in the free time for recreation.",,2021,Gemeente Edam-Volendam,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2021 +P29483,7430085010,Active and Connected Together,"Young people do something for others and/or society Young people have taken action to mean something to others and to broaden their horizons. Young people came into contact with a lonely older or young person in their spare time, expanding their network. Young people also entered healthcare organizations that were under pressure during Covid. Young people develop skills and work on their personal development Within Actief Verbonden, young people have learned new skills by connecting with others outside their comfort zone. New skills were also offered through the Skill and Chill evenings. They also came into contact with other young people who are committed to helping their fellow human beings. People from young to old and from different backgrounds meet each other (if possible) Actief Verbonden attracted young people from different educational levels and backgrounds. Young people with a migration background with language deficiency up to young people with a scientific level. All these different young people were also linked to older people or young people who in turn were different. By entering healthcare institutions, these young people have also come into contact with people who have disabilities in various areas. Social needs surrounding the coronavirus are being addressed Many young people who signed up were struggling with loneliness themselves and used this project as an opportunity to expand their network. The projects were aimed at the elderly who suffered from loneliness due to Covid. But the staff shortage that occurred in healthcare organizations during Covid is also a reason for this project. We also saw during the skill and chill evenings that young people really made new contacts and enjoyed the meetings and new experiences that were not possible for a long time.",,2021,Gemeente Veenendaal,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P29484,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center. This project is made possible by ZonMw",,2022,GGD Limburg-Noord,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29485,838002687,"scaling up project of first-line multidisciplinary rehabilitation as well as maintenance of resilience at a distance for vulnerable elderly people living at home, with or without a chronic condition, phase 2","Remote care is an effective treatment method for vulnerable elderly people and after surgery and an option to continue to follow a program frequently. This also applies if home treatment is temporarily not possible due to COVID-19. Together with partners from (para)medical healthcare and programs aimed at care, Manual-Fysiocare has developed a multidisciplinary online rehabilitation program: physiotherapy/occupational therapy, psychology and dietetics tailored to your needs and can be carried out remotely. To overcome the limited knowledge of digital resources, Manual-Fysiocare also wants to support this, because care must always be possible, even at home treatment is not possible. To ensure that the treatment is safe, a caregiver or informal caregiver is present during the initial phase and during the physiotherapy exercises. In the short term, we want to develop e-learning and communication material about the software and the program for greater support and a greater reach.",,2021,Fysiotherapie Daphne Bos,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Hospital personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29486,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Zeeland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29487,1.04302E+13,Corona Health Monitor Youth 2021,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,Dienst Gezondheid & Jeugd ZHZ,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29488,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Drenthe,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29489,1.04302E+13,Corona Youth Health Monitor in the context of GOR-COVID-19 part program - VGGM GGD Gelderland-Midden,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,Veiligheids- en Gezondheidsregio Gelderland-Midden,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29490,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-program - GGD Zuid Limburg,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Zuid Limburg,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29491,1.04302E+13,"Corona Youth Health Monitor in the context of GOR COVID-19 sub-program, 2021, GGD region Utrecht","Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Regio Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29492,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Amsterdam,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29493,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,Gemeente Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29494,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD West-Brabant,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29495,1.04302E+13,Corona Health Monitor Youth in the context of GOR COVID-19 sub-program - GGD Haaglanden,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Haaglanden,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Other,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29496,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Hart voor Brabant,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29497,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Groningen,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29498,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme. Contribution to GGD Brabant-Zuidoost,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD BZO,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29499,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Hollands Noorden,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29500,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Twente,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29501,1.04302E+13,Corona Health Monitor Youth Flevoland,"Corona Health Monitor Youth 2021 The corona crisis has an impact on everyone's life, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. At the end of 2021, the Corona Health Monitor Youth will take place at secondary schools in the Netherlands. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policymakers at local, regional and national level in policy formation. Based on the results, an appropriate care and support offer can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Flevoland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29502,1.04302E+13,Corona Youth Health Monitor 2021 GGD Gelderland-Zuid in the context of GOR COVID-19 sub-program,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Gelderland Zuid,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29503,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Amsterdam,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29504,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Zaanstreek-Waterland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29505,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,VRK - GGD Kennemerland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29506,1.04302E+13,Corona Health Monitor Youth in the context of GOR COVID-19 sub-program,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD/GHOR Fryslan,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29507,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD Noord en Oost Gelderland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29508,1.04302E+13,Corona Youth Health Monitor in the context of GOR COVID-19 sub-programme,"Corona Youth Health Monitor 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The government monitors the health effects of this crisis via the Integrated Health Monitor COVID-19. This monitor consists of various sub-studies aimed at young people, adults and the elderly. The Corona Youth Health Monitor will take place at secondary schools in the Netherlands at the end of 2021. The results will be published in May 2022 and provide insight into the impact of corona on the health, well-being and lifestyle of young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,GGD IJsselland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29509,1.04302E+13,HEALTH RESEARCH IN DISASTER - COVID 19,"Integrated Health Monitor COVID-19 Youth 2021 The corona crisis has a direct and/or indirect impact on everyone's health. The GOR network monitors the health effects of the crisis for the government via the Integrated Health Monitor COVID-19. In 2021, the focus will be on Youth, through literature research and short- and long-cycle monitoring research using questionnaire research and general practitioner registrations. The results will be published at various times in 2022 and provide insight into the impact of corona on young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the GOR network: RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,RIVM,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +P29510,1.04302E+13,Disaster Health Research-COVID-19. Monitor Youth 2021 and set up program,"Integrated Health Monitor COVID-19 Youth 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The GOR network monitors the health effects of the crisis for the government via the Integrated Health Monitor COVID-19. In 2021, the focus will be on Youth, through literature research and short- and long-cycle monitoring research using questionnaire research and general practitioner registrations. The results will be published at various times in 2022 and provide insight into the impact of corona on young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the GOR network: RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center. This project is made possible by ZonMw.",,2022,NIVEL,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions,2021 +P29511,1.04301E+13,Vaccination Against Covid in Primary Immune Deficiencies,"This study investigates whether patients with an innate immune disorder are protected against COVID-19 after vaccination. Patients with these congenital immune system disorders have an increased risk of developing infections and of a more serious course of infections. They may therefore also be more vulnerable to the serious course of COVID-19. It is therefore important that they are protected. However, it is not yet known how safe and effective the COVID-19 vaccines are in the group. Goal This project examines whether patients with an innate immune disorder actually become protected against COVID-19 after vaccination. Background In patients with congenital disorders, the immune system is less able to fight infections. This makes the risk of infections high. They may therefore also be more vulnerable to a serious course of COVID-19. Protection against COVID-19 through vaccination is therefore crucial for these patients, but due to the reduced immune function, the vaccine may be less effective or provide protection for a shorter period of time. Research design After vaccination, blood is tested at a number of times to see whether protection occurs in the immune system against COVID-19 and whether this protection lasts for a longer period of time. In addition, it will be investigated whether these patients still contract COVID-19 despite vaccination. Expected results Insight into whether corona vaccines work safely and effectively in patients with congenital disorders. This can translate into individualizing the vaccination strategy, including giving additional booster vaccination for those who are insufficiently protected.",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P29512,838002655,E-health implementation and scaling up TK Huisarts,"We mainly offer traditional care where patients are often treated in practice, regardless of whether physical contact is necessary. Due to Covid-19, the space for receiving patients is very limited, as full waiting rooms are no longer allowed. (Infected) employees often work from home, there is insufficient space to keep their distance. Inviting patients for physical contact should be limited as much as possible to reduce the risk of transmission. We want to seize this moment to also cope with personnel pressure and the double aging of the population in the future. With implementation coaching we want to implement video calling and telemonitoring in a sustainable manner in our practice.",,2021,Huisarts Tekin Karakose,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29513,838002658,Scaling-up coaching for embedding video calling consultations via Beter Dichtbij in existing care pathways,"The COVID pandemic has increased the importance of communicating with patients remotely. Many physical consultations have been converted into telephone consultations using the BeterDichtbij app. For patients and doctors, a large part of communication is missed during a telephone consultation (non-verbal communication). Embedding Better Close in existing care pathways is being tackled through this project. In this project with a duration of two months, a scale-up coach from BeterDichtbij is deployed to actively involve employees and patients in this process. The upscaling coach offers the hospital support in the further rollout of the BeterDichtbij app, provides advice on how to scale up (tips & tricks) and uses examples from other hospitals. Actively involving employees and patients in this process contributes to the intended goal of increasing the number of BeterDichtbij conversations by 50% in 2021. This project is made possible by: ZonMw.",,2021,Spijkenisse Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Not applicable,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Communication | Health service delivery | Health information systems,2021 +P29514,838002661,Request Implementation and scaling-up coaching (round 3),"The corona crisis is a difficult period for our patients. It is important for this group to keep moving to reduce the risk of complications and co-morbidity and to promote recovery. It is sometimes difficult to figure out how we can continue all forms of care and guidance within Phaedra during this period of corona measures. Some forms of offering are now only physically available and cannot be offered in groups. This means that COVID-19 has a very hindering effect on both our existing client group and the newly reached client group as referrers. By prioritizing e-health in our practice, we can provide care to seriously ill and, in many cases, chronically ill people. With remote treatment and guidance from Phaedra's therapists, they can maintain their condition, reduce the risk of complications, undergo the treatments physically and mentally stronger and prevent them from becoming lost in the isolation of the moment.",,2021,Phaedra centrum voor oncologische zorg,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +P29515,1.04301E+13,Investigating the immune response to COVID-19 VAccination in Lung Transplantation patients (COVALENT study),"COVID-19 is extra dangerous for people with a lung transplant and people on the waiting list for a lung transplant. For example, an infection can lead to damage or rejection of the transplanted lungs, and it can lead to such deteriorated lung function that people are no longer recommended for transplantation. It is important that a vaccination protects these patient groups against infection as best as possible. There is not yet enough knowledge about whether COVID-19 vaccines are safe for these patient groups and whether they work well. This is investigated in this study. Goal The main goal is to investigate whether the production of antibodies and immune cells against the coronavirus after COVID-19 vaccination in lung transplant recipients is as good as in other people. In addition, research is being conducted into whether people on the waiting list for a lung transplant, and who are vaccinated before they are transplanted, also remain protected after lung transplant. Research design This study follows three patient groups who are vaccinated against COVID-19. This concerns adults who have undergone a lung transplant, adults who are on the waiting list for a lung transplant and adults who have undergone a lung transplant and have had a COVID-19 infection. They have regular blood samples taken before vaccination and up to a year after vaccination to monitor the immunity response. The blood is measured to determine whether immune cells and antibodies are formed after vaccination. It is then examined how long those immune cells and antibodies remain present. Participants in the study complete questionnaires about the complaints they experience after the vaccinations. These people are also checked to see whether they still contract COVID-19. Expected results After this study, it is known how effective COVID-19 vaccination is in preventing infection in these patient groups after 28 days, after six months and after one year. It will also become clear whether the vaccines are safe for these groups.",,2025,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity | Adverse events associated with immunization,2021 +P29516,1.04301E+13,"COBRA-KAI study: COVID-19 vaccination in patients with reduced B-cell and T-cell immunity: response after vaccination of a kaleidoscopic group hematological patients, what's the impact?","In patients with an underlying hematological disease, vaccination is often refrained from, because it is still questionable whether vaccination provides sufficient protection. This study investigates whether this is correct. The researchers expect to be able to identify patient groups that, contrary to expectations, respond well to vaccination. It is also being examined whether patients who are insufficiently protected after vaccination can be given additional protection by vaccinating household members (ring vaccination) and whether patients themselves can be given a 'booster' vaccination. Goal Mapping specific patient groups that are (in)sufficiently protected after the standard COVID-19 vaccination schedule, and whether one or more additional (booster) COVID-19 vaccination(s) for patients who are insufficiently protected leads to adequate protection against COVID-19. Background COVID-19 additional risk in hematological diseases Patients with a hematological disease, such as leukemia or lymphatic cancer, often have a weakened immune system. This greatly increases the risk of a serious course of a COVID-19 infection. For example, the risk of death from sickle cell disease is even 6 times greater. Doubts about the effect of vaccination At the same time, it is questionable whether vaccination works well in these patients, because their immune system may be less able to build up immunity. This may be due to the disease itself or due to treatments that suppress the immune system. This is the reason why vaccination is often refrained from in these patients. Additional knowledge required for optimal protection To optimally protect this patient group, more research is needed into the effect of COVID-19 vaccinations. This study not only examines whether patients with a hematological disease are well protected after vaccination, but also whether one or more additional (booster) COVID-19 vaccination(s) leads to adequate protection in patients who do not build up sufficient immunity. after standard COVID vaccination schedule, and how long this protection lasts. After all, shorter protection may be a reason for additional vaccination. The researchers will also map parts of the immune system that predict which patients can build up a good immune system and which cannot. The results of this research will be used to improve vaccination guidelines and advice. Research design We follow 850 patients In this study, we will measure the response of the immune system to the vaccination in 850 patients with hematological diseases who are vaccinated against COVID-19. For this purpose, blood is taken from patients both before vaccination and at fixed time points afterwards. Various aspects of the immune response against SARS-CoV-2 will be measured in this blood, such as antibodies and the functioning of cells of the immune system (B and T cells). Data from patients will also be collected, such as the precise hematological diagnosis, previous anti-cancer treatments, current treatment and medication use. Booster vaccination Patients who have not built up sufficient immunity after a standard COVID vaccination schedule will receive a booster vaccination, after which it will be investigated whether sufficient immunity has been built up or whether an additional booster vaccination is needed. Patients who initially show a response to the standard vaccination schedule but do not show sufficient immunity after 6 months will also receive a booster vaccination. Expected results After the research, we expect to be able to identify patient groups that, contrary to expectations, respond well to the standard vaccination schedule. On the other hand, we can define patient groups in which it is possible to build up adequate immunity against COVID-19 through booster vaccinations. For patients who are insufficiently protected even after booster vaccination, additional protection can be generated after vaccination by vaccinating housemates (ring vaccination). This knowledge can also be applied to annual vaccination campaigns against flu and other pathogens.",,2025,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation | Pathogen: natural history, transmission and diagnostics",Characterisation of vaccine-induced immunity | Immunity,2021 +P29517,1.04301E+13,sars-COv-2 Vaccination response In people living with HIV - COVIH study,"The immune response to corona vaccines is unknown in people living with HIV. As observed with other vaccines, this immune response may be reduced by the immune status of individuals living with HIV. This research studies the immune response to vaccination and identifies the side effects. The course of the immune response will then be studied over the next few years. Goal The aim of this research is to study the immune response to vaccination among people with HIV and to map the side effects. Background Although people living with HIV (PLHIV) can now lead a normal life thanks to HIV inhibitors, their immune system does not always appear to function normally. Previous vaccination studies with, for example, Influenza or Hepatitis vaccines, often showed that the immune response to these vaccines was reduced or even absent. It is unknown how PLHIV respond to the new COVID-19 vaccines. Research design In this study in 22 HIV centers, the antibody responses of PLHIV against the various COVID-19 vaccines will be compared with the responses of people without HIV, 4 weeks after completion of the vaccination. More extensive research is being conducted into, among other things, the cellular immune response in a smaller group of patients. Through the ongoing follow-up via the HIV Monitoring Foundation, the duration of the antibody response and the incidence of new SARS-CoV-2 infections will be analyzed. Expected results The results of the study will be used to provide advice on the use of COVID-19 vaccines in PLHIV.",,2024,OLVG,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation | Pathogen: natural history, transmission and diagnostics",Adverse events associated with immunization | Characterisation of vaccine-induced immunity | Immunity,2021 +P29518,838002649,How can we best inform new clients and their parents and referrers about our options for online care so that the continuity of guidance is guaranteed during this time and people can find the right care.,"Current developments regarding the COVID-19 virus show that e-health is a valuable addition to healthcare interventions. Due to unfamiliarity with both clients and referrers, this is not yet being used optimally. The result is that clients have to wait too long before they get to the right place for their care. Movement in Development wants to integrate e-health into the intervention program that has been specially developed for families with a child with long-term pain or fatigue complaints. Our goal is that referrers can refer easily and families can find us easily. This way they can experience the benefits of a mix of face-to-face consultations with e-health consultations. By using digital forms of guidance, fewer face-to-face treatments are required and the self-reliance and independence of parents and children within their recovery process is increased. This reduces healthcare costs and saves on labor. The digital resources strengthen the quality of care, because encouraging self-reliance and independence also ensures a better result and faster recovery. Recovery and insight into their own health in the broadest sense of the word ensures an increase in the quality of life of the children and their families.",,2021,Beweging in Ontwikkeling,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29519,1.04301E+13,Renal patients COVID-19 vaccination (RECOVAC) consortium,"COVID-19 is a dangerous virus and can have fatal consequences. There are groups of people who even have an increased risk of dying from this, for example kidney patients. The chance that a kidney patient will die from the virus is 4 times greater than a person from the general population. An effective vaccine is desperately needed for this group of people, but it is known that existing vaccines generally work less well in kidney patients. Whether this is also the case for COVID-19 vaccines, why this may be the case and how this group can still be protected is what this research is about. All Dutch universities are working together on this research in a consortium called RECOVAC. Four studies have been set up within the research. Goal The goal is to protect kidney patients as best as possible against COVID-19. The 4 studies also have their own purpose: RECOVAC Immune Response study: Investigate in detail the response of the immune system to COVID-19 vaccination in kidney patients. RECOVAC Antibody study: investigating the relationship between antibody response and protection against COVID-19. RECOVAC Registration study: the occurrence and severity of COVID-19 after vaccination in kidney patients compared to the general population and to people who have not been vaccinated. RECOVAC Booster study: investigate the response of the immune system and the occurrence of COVID-19 after different booster vaccination strategies in patients who have not produced antibodies after two administrations of the Moderna vaccine. Background Why are these studies necessary? Before vaccinations are approved and vaccinations actually take place, a lot of research has been done into the operation and effect of these vaccinations. Unfortunately, there is a lack of specific research into the operation and effect of vaccinations in certain vulnerable target groups, such as kidney patients. Protection is especially important for them, because kidney patients and other patients with a compromised immune system are much more likely to become seriously ill or even die if they become infected with COVID-19. Research design RECOVAC Immune Response study The RECOVAC Immune Response study investigates the response of the immune system of kidney patients after COVID-19 vaccination. This study examines the immune system after vaccination in 175 patients with severe kidney damage, 175 dialysis patients and 300 kidney transplant patients. The results of these groups are compared with the control results of 200 people with normal kidney function. Blood is taken prior to vaccination, 28 days after the first and second vaccination, 6 and 12 months after the second vaccination. Antibodies are measured at different times, but other forms of defense are also examined. RECOVAC antibody study The second study focuses on the relationship between the level of antibodies and the (long-term) efficacy of COVID-19 vaccination. Patients with severe kidney damage, dialysis patients and kidney transplant patients are widely invited to take blood samples at home by means of a finger prick and send them 28 days and 6 months after complete vaccination. This blood is then tested for specific antibodies that are produced after vaccination. In addition, it is recorded whether someone still becomes infected with COVID-19 by means of a questionnaire that is administered 28 days, 6 months, 1 and then 2 years after complete vaccination. This will investigate a relationship between the production of antibodies after vaccination and the risk of still becoming infected with COVID-19. RECOVAC registration study This study aims to investigate the long-term efficacy of COVID-19 vaccination in dialysis patients and kidney transplant patients. It will be examined whether someone still becomes infected with COVID-19 after vaccination and to what extent and whether this differs from people in the general population or from people who have not been vaccinated. It will also be examined whether there are certain patient characteristics that could increase this risk. For this research, a large registry will be kept of all dialysis and kidney transplant patients in the Netherlands and links to existing registries will largely be used. This research will last 2 years. RECOVAC booster study This study aims to provide essential, missing information about the optimal COVID-19 booster strategy in patients for whom no antibodies are detectable after the two standard administrations of the Moderna vaccine. It is also important to investigate whether there are better methods than just repeated administration of vaccine if there are patients who produce insufficient or no antibodies even after a booster vaccination. The first results The first results will be on November 9, 2021 of the RECOVAC Immune Response study published online in Transplant Journal",,2025,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Impact/ effectiveness of control measures | Prognostic factors for disease severity | Characterisation of vaccine-induced immunity,2021 +P29521,1.04302E+13,Corona Youth Health Monitor 2021 and setting up COVID-19 program,"Integrated Health Monitor COVID-19 Youth 2021 The corona crisis has an impact on everyone's lives, directly and/or indirectly. The GOR network monitors the health effects of the crisis for the government via the Integrated Health Monitor COVID-19. In 2021, the focus will be on Youth, through literature research and short- and long-cycle monitoring research using questionnaire research and general practitioner registrations. The results will be published at various times in 2022 and provide insight into the impact of corona on young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the GOR network: RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center. This project is made possible by ZonMw",,2022,GGD GHOR Nederland,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29522,1.04301E+13,Immunity against SARS-CoV-2 in immune-suppressed patients: increased risk of insufficient immunological memory or sufficient protection against re- infection - a Target to B! substudy,"It is not yet clear in healthy people how long they are protected against the SARS-CoV-2 virus after an infection and/or vaccination. In patients with an autoimmune disease, the uncertainty about the degree of protection and duration of protection is even greater. They generally use immunosuppressive (immunosuppressive) medication (ISM). This research focuses on the effectiveness of COVID-19 vaccination in this patient group and examines whether specific immunity to SARS-CoV-2 decreases over time in relation to the underlying autoimmune disease and the medication used. Goal The aim of this study is to investigate whether COVID-19 vaccination sufficiently protects patients with an autoimmune disease against a COVID-19 infection. Background Patients with autoimmune diseases often use immunosuppressive medications (ISM). It is unclear whether the COVID-19 vaccinations are equally effective in this group of patients and under what circumstances effective protection may be insufficient. Research design In this national study, the vaccination responses of patients with different ISM are compared with the responses of patients without ISM and healthy subjects. Most participants collect blood at home with a finger prick set and complete questionnaires about the course of their disease and side effects. The amount of antibodies against the virus is measured in the blood sent. The underlying mechanisms are studied in detail in a smaller group of patients. Expected results Determine whether ISM plays a role in the effectiveness of the vaccination and to what extent, depending on the type of ISM. The researchers also hope to determine whether the vaccinations are completely safe. These results will be used to provide advice on the need for repeat vaccinations.",,2025,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2021 +P29523,1.043E+13,"Upholding human rights in a pandemic: The Social Impact of COVID-19 measures on vulnerable families in Curacao, Aruba and St. Maarten","The COVID-19 pandemic has strained the economies, health-care systems, social structures and living standards on the islands Curaçao, Aruba and St. Maarten. Using a human rights-based approach this multidisciplinary study will focus on the social impact of the COVID -19 pandemic and the State responses towards protecting vulnerable families. We apply a multi-sited, mixed-methods approach to understand the diverse reasons that contribute to increase in vulnerability and measures that can be taken to build social resilience among families and communities. This study will also evaluate the performance of COVID-19 measures and make recommendations for futures outbreaks and epidemics.",,2023,Curacao Biomedical & Health Research Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2021 +P29524,1.04301E+13,VOICE: Vaccination against cOvid In CancEr,"Patients with cancer who are treated with immunotherapy and/or chemotherapy are at extra risk of a serious course of a COVID-19 infection. It is therefore important for them that they are optimally protected by vaccination. However, we do not know whether the COVID-19 vaccines are safe and effective for this patient group. This study aims to assess the immune response and side effects after administration of vaccination against COVID-19 in these patients. Goal To assess the immune response and side effects after administration of vaccination against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy. Research design In this study, four groups receive the two vaccinations against COVID-19 prescribed by the manufacturer. After vaccination, the immune response and any side effects are assessed for each of them. A. Control group: the partners of the patients in groups B. C and D. B. People with cancer treated with immunotherapy. C. People with cancer who are being treated with chemotherapy. D. People with cancer who are treated with both immunotherapy and chemotherapy. The primary endpoint is the antibody-based immune response on day 28 after the second vaccination. The percentage of responders in each patient cohort is compared with the percentage of responders in the control group. The secondary objectives are 1) safety (rate of local and systemic side effects for each patient group), 2) duration of response and 3) extent of SARS-CoV-2 specific T cell responses. Participants record responses for seven days after each vaccination and blood is taken at multiple times up to 12 months after vaccination. The first results The first results will be on November 9, 2021 of the research published in the scientific journal The Lancet Oncology. The results show that most cancer patients who receive chemotherapy, immunotherapy or both against solid tumors with two mRNA vaccines produce sufficient antibodies against COVID-19. The vaccine is also safe for these patients. However, a small group is not protected and may benefit from a third injection.",,2025,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +P29525,838002636,Resilience in COVID-19 Care Project (RECCAP): Care for healthcare professionals with the Digital Stress Buddy,"Healthcare workers are exceptionally resilient, as they have proven in recent months. However, a series of traumatic events can also lead to overload and stress-related complaints for them. The Stress Buddy makes users aware of their stress and energy levels at a glance. The app is an accessible way to identify possible problems in a timely manner. Every week they complete a questionnaire about stress and energy sources. Based on the score, a battery will appear that turns green, orange or red, including appropriate tips. Many of the COVID-19 related studies have been conducted in hospital settings. This is striking, as primary care and nursing homes are also under considerable pressure. The innovative nature of this project lies in the expansion of psychological monitoring beyond the walls of the hospital.",,2021,Leiden University Medical Center,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health | Innovation,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29526,838002631,Medxpert COVID-19 pilot,"With a personal health environment (PGO), a patient retrieves his medication data from, for example, his GP, pharmacy and hospital. With the medxpert app (a PGO) you always have that data with you, on your phone or tablet. The medxpert contains more, such as a corona questionnaire and a repeat prescription function. Zorgbelang will support patients of the Asten pharmacy in using the app. They also investigate the following points with a user group: The functions and user-friendliness of the medxpert app; The use of the corona questionnaire within the medxpert app. This gives the user insight into the risk of infection with the coronavirus and the risk of complications; The influence of the use of the functions in the medxpert app on the care process at the pharmacist and GP; Opportunities for the large-scale use of the medxpert app and possible areas for improvement.",,2021,Medxpert,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Epidemiological studies | Clinical characterisation and management | Health Systems Research,Disease susceptibility | Prognostic factors for disease severity | Health service delivery | Health information systems,2021 +P29527,1.03901E+13,Remote atrial fibrillation management through teleconsultation vs. standard of care: The TeleCheck-AF randomised controlled trial.,"Due to the COVID-19 pandemic, it is currently not desirable to physically see stable patients with atrial fibrillation in the outpatient clinic. For this reason, a new mHealth infrastructure has been developed at the MUMC+, which enables remote care through app-based heart rate and rhythm monitoring for patients with atrial fibrillation via telephone consultations: TeleCheck-AF. The effectiveness and feasibility of this approach has already been proven, but the cost-effectiveness is still uncertain. For this reason, the aim of this project, set up with various partners, is to investigate whether the TeleCheck-AF approach is as cost-effective as current standard care. The expectation is that the TeleCheck-AF approach will result in a better quality of life and lower costs, because (unnecessary) visits to the outpatient clinic can be avoided.",,2021,Maastricht University,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P29528,1.04302E+13,Health research during COVID-19 disasters,"The corona crisis has a direct or indirect impact on everyone's health. The GOR network monitors the health effects of this crisis for the government via the Integrated Health Monitor COVID-19. In 2021, the focus will be on Youth, through literature research and short- and long-cycle monitoring research, using questionnaire research and general practitioner registrations. The results will be published at various times in 2022 and provide insight into the impact of corona on young people. The aim of the monitor is to support policy makers at local, regional and national level in policy making. Based on the results, an appropriate care and support offering can be set up with the aim of limiting the negative health effects of the crisis. The monitor was developed by the GOR network: RIVM, the GGDs, GGD GHOR Netherlands, Nivel and ARQ National Psychotrauma Center.",,2022,ARQ National Psychotrauma Centre,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Indirect health impacts,2021 +P29529,1.04301E+13,Prospective monitoring of antibody response following COVID-19 vaccination in people with Down syndrome (PRIDE study),"The immune system in adults and children with Down syndrome functions less well. This puts them at higher risk of complications from a COVID-19 infection. It is therefore important for them that they are optimally protected by vaccination. It has not yet been investigated whether the reduced functioning of the immune system also affects the effectiveness of vaccinations against COVID-19. This study aims to assess the immune response and side effects in people with Down syndrome after administration of vaccination against COVID-19. Goal To assess the immune response and side effects after administration of vaccination against COVID-19 in adults and children with Down syndrome. Background People with Down syndrome have a higher risk of becoming seriously ill from the new coronavirus. They will therefore be among the first to be vaccinated against the coronavirus. Previous research shows that vaccinations work less well in people with Down syndrome. The PRIDE study examines whether the corona vaccine provides sufficient protection for adults and children with Down syndrome. Research design The immune response is examined by taking blood samples and taking nasal mucus around the vaccinations and one year after the second vaccination. The results will be compared with people without Down syndrome. Since the end of June, children have also been allowed to participate in the study. First results The first results of the PRIDE study were published on November 17, 2021 . The research shows that adults with Down syndrome, after vaccination with Moderna or Pfizer, have a lower concentration of neutralizing antibodies against COVID-19 than people without Down syndrome. After vaccination with AstraZeneca, there are no differences between the two groups. The question remains what exactly these results say about protection against disease. The minimum concentration of neutralizing antibodies required for this has not yet been determined. For people with Down syndrome, data on the cellular response, which is also important for protection, is not yet available.",,2025,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2021 +P29530,1.04301E+13,The Convalescent plasma (ConvP) and COVig PK/PD study: a study into the usefulness of treatment with antibodies from plasma to treat or prevent the coronavirus (SARS-CoV-2),"In the ConvP/COVIg PK/PD study we have test subjects who do not produce antibodies themselves against the coronavirus treated with convalescent plasma or hyperimmune globulins (COVig). Previously, there were no studies that investigated how much plasma or COVig should be given be used to ensure that a patient receives sufficient amounts in the weeks or months after administration has antibodies in his/her blood. In this study, blood was taken at fixed times after administration of the plasma or COVig and investigated how many antibodies against the coronavirus were present and for how long. On base From these measurements we built a model that, after administration of plasma or COVig, the can predict the concentration of antibodies in the blood. The study showed that the plasma used in the first year of the COVID19 pandemic cured patients were taken from too few antibodies compared to people without antibodies long-term protection. The developed model can provide a method for the design of future studies to the preventive or therapeutic use of these agents can be used (e.g. against other viruses).",,2023,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,Unspecified,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity,2021 +P29531,1.04303E+13,Multidisciplinary comprehensive guideline for COVID-19 aftercare,"Over the past year, various parties have developed documents aimed at aftercare for COVID-19 patients. Unfortunately, these do not always appear to correspond well with each other, sometimes provide different advice and were written in a period when little scientific literature was available. More and more is becoming known about the long-term complaints of patients. Goal In this project, an up-to-date multidisciplinary integral evidence-based guideline is being developed aimed at aftercare (>4 weeks after infection) for all COVID-19 (suspected) patients, regardless of the context in which they experienced the disease. The Knowledge Institute of the Federation of Medical Specialists and the Dutch Society of General Practitioners (NHG) provide process and methodological support in the development of this guideline. The guideline is published on the Guidelines Database and included on the NHG Guidelines website. Research design The various documents have been compared and merged into one comprehensive guideline. Results The guideline was introduced in March 2022 published and presented to the Minister of Health, Welfare and Sport. Guideline 'Long-term complaints after COVID-19' (NHG guideline database) Patient information on Thuisarts.nl",,2022,Nederlands Huisartsen Genootschap,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2021 +P29532,1.03901E+13,Effectiveness of allied healthcare in patients recovering from COVID-19,"An inventory by the Lungfonds shows that more than half of the people who had a COVID-19 infection still experience multiple complaints after six months. Less than 5 percent are completely free of complaints. First-line paramedical care, consisting of dietetics, occupational therapy, physiotherapy, speech therapy and/or exercise therapy, may contribute to the recovery of these patients. In this study, we follow patients who recover from a COVID-19 infection and visit a paramedic over time. We use data that have already been collected in the past from people who visited paramedical care providers using databases and treatment files. We also follow new patients with questionnaires and (physical) tests. Here we are mainly interested in the outcome measures: fatigue, participation, and quality of life. Finally, we interview patients (and their loved ones), paramedics and referrers about their experiences with paramedical care.",,2023,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Post acute and long term health consequences,2020 +P29533,838002623,"Care safely at home with digital support. Care pathway: COPD/Corona, Diabetes, IBD, Osteoarthritis and Osteoporosis","The care safely at home project using digital support for the COPD/Covid/Diabetes/IBD/Osteoarthritis and Osteoporosis care pathways is a project that is part of the JZOJP program. The aim is to keep a better track of 2nd line patients through remote monitoring and to be able to intervene earlier if necessary. These interventions should lead to a lower frequency of outpatient clinic visits, a shorter length of stay, a decrease in the number of readmissions, higher patient satisfaction, higher professional job satisfaction and, in the long term, a reduction in healthcare costs. This complies with the Quadruple-Aim principle. A project team has been formed for each care path, consisting of: A medical specialist, a nursing specialist or specialist nurse, a tactical and operational manager from the line, an internal process supervisor from the JZOJP program and an external implementation coach and patient council.",,2021,Zaans Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19 | Other,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +P29536,838002552,Scaling up the use of Telerehabilitation in preparation for rehabilitation treatment.,"In this project, Roessingh, center for Rehabilitation, is working with Kim Peters from Healthnovum to scale up the use of the Telerehabilitation portal. Telerehabilitation offers the patient the opportunity to carry out parts of the rehabilitation treatment independently at home. Due to the COVID-19 outbreak, the use of Telerehabilitation gained momentum. In order to be able to respond more to the wishes and needs of patients, informal caregivers and practitioners, Kim Peters will talk to them and analyze and evaluate questionnaires regarding the use of online treatments. These results are brought together by Kim with the latest scientific insights and IT possibilities. Based on this, she advises Roessingh. This allows Roessingh to respond even more to the needs of patients, informal caregivers and practitioners when using digital support for rehabilitation treatments.",,2021,Revalidatiecentrum Het Roessingh,,Human Populations,Unspecified,Adults (18 and older) | Unspecified,Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29537,1.043E+13,Is our environment future-proof for sufficient physical activity in a 1.5m society?,"Our living environment is not designed for keeping a distance of 1.5 meters. Since March 2020, a decrease in exercise patterns has also been seen. An inactive lifestyle is a predictor of health problems. Therefore, the expected long-term health effects of COVID-19 will be stronger in less exercise-friendly neighborhoods. These are often neighborhoods with a low income and education level. Research Active exercise behavior is monitored in various lockdown stages through ongoing medical studies. Outdoor areas where exercise patterns decrease the most are investigated by means of: an urban development analysis. Together with 12 municipalities, interventions are being investigated that make outdoor spaces more suitable for a healthy 1.5 meter society. Expected outcomes A measuring instrument for the exercise-friendliness of the living environment: the Exercise Place Meter, an intervention package for municipalities and a GGData platform addition that provides insight into spatial bottlenecks and solutions.",,2022,Radboud Universiteit Nijmegen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29538,1.043E+13,Is COVID-19 a threat to banks and financial stability in Europe?,"The COVID-19 pandemic has a huge impact on the economy. The global economy is expected to shrink by as much as 5% in 2020, even more than during the 2008-2009 financial crisis. The length and depth of this recession will largely depend on the impact of COVID-19 on banks, given their central role in the economy. However, this impact is difficult to assess, because banks estimate the losses on their outstanding loans based on outdated accounting data. Banks and regulators urgently need an up-to-date estimate of expected losses from COVID-19 so that they can take measures if financial stability is at risk. In this project, a new method is being developed to estimate these losses in real-time based on market valuations and the option valuation model of Nobel Prize winner Robert Merton. The method is applied to European banks and the market valuations of 1,981 European listed companies in 19 sectors.",,2022,Erasmus University,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29539,1.043E+13,Child and adolescent mental health and wellbeing in times of the COVID-19 pandemic;Elucidating intervention targets to decrease mental health problems and optimize wellbeing in Dutch children with and without a history of mental problems.,"Children and young people are less vulnerable to the medical consequences of COVID-19. Yet the corona measures will also hit them hard. However, stories are also heard about children and young people who experience the corona measures as pleasant. They benefit from the peace, structure and reduction of pressure that normal life brings. We will systematically investigate the effects of the corona measures on their mental health and well-being in large samples of Dutch children and young people (with and without prior mental problems). Our findings will result in recommendations for prevention and interventions at national, regional and individual levels. Children and young people will be actively involved in this research. By carefully mapping the consequences of the corona measures on the mental health of Dutch youth, we hope to be optimally prepared for future developments in the pandemic.",,2023,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29540,1.043E+13,Inequality in sport and exercise under COVID19: The impact of sport for a resilient society,"After education, the sports sector was the first to start up after the lockdown. Sport is considered important to alleviate problems resulting from the corona measures and thus contribute to a resilient society. But how is it achieved that citizens are active? Poverty, care tasks, social isolation and/or health issues - caused or reinforced by the corona measures - can create (too) high barriers to participation in sports and exercise. That is why changes in sports and exercise behavior of the population and of specific target groups are studied to see whether social inequality in sports is increasing or decreasing. In addition, the experiences of specific target groups during COVID-19 and the effectiveness of policy efforts to allow everyone to participate and optimize social value are discussed. Together we are able to arrive at guidelines for a society in which everyone can (continue to) participate in sports and exercise.",,2023,Radboud Universiteit Nijmegen,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29541,1.043E+13,Mobility- and behavior-based early-warning system after the first wave of COVID-19,"Who: Consortium of experts in public health, eHealth, behavioral sciences, mathematical epidemic modeling, governance and data analytics. What: Interactive dashboards are being developed to support decision-making regarding local lockdowns. These dashboards are complementary to the dashboards being developed by the Dutch government, because they contain new types of information: regional, current trends in risky behavior, and mobility between regions. When: October 2020 - March 2022. The first prototype dashboards will be available in early 2021. How: Mathematical models are used to quantify risk predictions and develop an early warning system in the form of interactive dashboards. To achieve implementation, the response from policymakers is used as input to improve the dashboards. Why: This project helps make informed regional decisions in a timely manner to contain the spread of the virus.",,2022,Technische Universiteit Eindhoven,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Data Management and Data Sharing,,,,,"Epidemiological studies | Infection prevention and control | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities | Policy research and interventions,2020 +P29542,1.043E+13,Opportunities in Crisis: how do schools shape educational partnerships?,"The COVID-19 crisis means that schools must respond resiliently. They have to adapt very quickly to unforeseen circumstances. The big challenge is to maintain the quality of education at the same time. Disadvantaged students are most at risk. There is a great danger that they will develop even greater educational disadvantages during this period. The resilience of schools in secondary education (VO) will be studied over the next 2 years. Goal How do schools collaborate with parents of underprivileged students and how can they strengthen this collaboration? The aim of the project is to provide secondary schools with support in (strengthening) this collaboration. Research design The research takes place in the regions of Amsterdam and Nijmegen. The study takes place in three phases. After each phase, insights are immediately shared with secondary schools in the Netherlands. In the second year, the initial findings are used to develop and test interventions in collaboration with schools. (First) results The report was published in 2021: 'How five MBO schools entered into partnership with the parents of vulnerable students during the COVID-19 crisis '. These research results show how schools can respond resiliently to a crisis situation. Executive parties University of Amsterdam, Radboud University Nijmegen, BMC",,2024,Universiteit van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29543,838002549,Multidisciplinary remote rehabilitation for low-resilience clients under the Wmo.,"Remote care is an effective treatment method for vulnerable elderly people and after surgery and an option to continue to follow a program frequently. This also applies if home treatment is temporarily not possible due to COVID-19. Together with partners from (para)medical healthcare and programs aimed at care, Manual-Fysiocare has developed a multidisciplinary online rehabilitation program: physiotherapy/occupational therapy, psychology and dietetics tailored to your needs and can be carried out remotely. To overcome the limited knowledge of digital resources, Manual-Fysiocare also wants to support this, because care must always be possible, even at home treatment is not possible. To ensure that the treatment is safe, a caregiver or informal caregiver is present during the initial phase and during the physiotherapy exercises. In the short term, we want to develop e-learning and communication material about the software and the program for greater support and a greater reach.",,2021,Fysiotherapie Daphne Bos,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29544,1.043E+13,Learn to dance. Governing healthcare in times of a pandemic (Learning to dance. Governing healthcare in pandemic times),"In this project we conducted ethnographic research into decision-making in healthcare during the corona pandemic. We were particularly interested in the question of whether and how decision-making can be adaptive; that is, can adapt to changing circumstances and uncertainties-and to what extent decision-making contributes to the resilience of healthcare. To this end, we made observations at three regional consultations for acute care and we also conducted interviews with nurses, doctors, patient representatives, administrators, policy makers and supervisors. We also collected and analyzed many documents. We find that governance has been only partially adaptive. Lessons have been learned during the pandemic-for example with regard to non-COVID care-but problems in long-term care, for example, have only been addressed to a limited extent. Representation of patients and 'the work floor' has only gradually taken shape. We make several recommendations to make healthcare more resilient. Goal This project focuses on the organization of decision-making. Looking back, we want to learn from the first and second waves of the pandemic. Looking ahead, we are trying to learn lessons with the actors involved. The starting point is that a form of 'adaptive governance' is needed; a board that can adapt to unexpected and uncertain circumstances. Background The virus will be with us for a long time and that means we have to learn to live with it. We use the metaphor of dance to give substance to this adaptive handling of the virus. How can we learn to dance (better)? We hope to contribute to this by following decision-making processes and reflecting on them together with those involved. Research design The questions this project answers are: Looking back, what can we learn from the administrative response to the Corona crisis about the management of care in times of pandemic crises? How can the dance of local, regional and national administrative arrangements be effectively shaped in the 'chronic' phase of the crisis and which parties can positively influence this? What effects does this dance and the resulting decisions have on the organization and implementation of healthcare? The project is designed as an action research in which data is collected through interviews, observations and document analysis, which is reflected on in regularly held sessions with partners. We build on data that has already been collected in recent months. The project results in recommendations for the organization of decision-making for healthcare in pandemic times, as well as in scientific publications.",,2022,Erasmus School of Health Policy & Management,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff | Physicians | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Health Systems Research,Health service delivery | Health leadership and governance,2020 +P29546,1.043E+13,ICU triage during a crisis: learning to apply medical and non-medical criteria to patient cases,"Suppose that almost all intensive care places (IC places) are occupied during a pandemic, how should healthcare providers make a choice between patients who need an ICU place? Two scripts have been developed in the Netherlands for this purpose, with medical and non-medical rules that teams of healthcare providers must follow when making such a choice (this is called ""triage""). In this study, healthcare providers applied these rules to imagined (non-real) patients based on their patient records. This showed that the Dutch rules can be used well. Both healthcare providers and citizens also broadly agree with the content of the rules. In order to apply the rules properly and carefully, it is useful if healthcare providers in triage teams are given an explanation of the rules in advance and practice applying them. That is why e-learning for healthcare providers has been developed as one of the end products of this project. Read more about ethics and health More information about research into corona and COVID-19",,2023,Radboudumc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Health Systems Research,Health leadership and governance,2020 +P29547,1.043E+13,POLAR: Psychosocial effects of corona measures in people with Alzheimer's,"POLAR aims to make people with Alzheimer's more resilient to the consequences of the corona measures. They are having a hard time during corona. Not only are patients extra susceptible to the virus, informal caregivers are also hit hard by the measures. Most people with Alzheimer's live at home and use (in)formal care and support networks. Formal care concerns, for example, case management and daytime activities and these have often stopped due to the measures. This has increased the pressure on informal caregivers considerably. POLAR maps the effects of corona on the patient's behavior, mood and functioning, burden on loved ones and care use. In addition, online information tools are being developed about dealing with the consequences of the corona measures. This contributes to positively influencing the support system around people with Alzheimer's during and after COVID-19. POLAR is a collaboration between the Amsterdam Alzheimer Center, Amsterdam UMC, Alzheimer Netherlands and Pharos. First results During the second lockdown, patients and healthcare providers adapted better to the challenges of the lockdown. The psychosocial and behavioral effects decreased and patients experienced more social support compared to the first lockdown. Support from family and friends appears to be an important protective factor for negative outcomes in patients and caregivers. The first results were published in January 2022 published in the Journal of Alzheimer's Disease.",,2023,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29548,1.043E+13,Critical materials in crisis,"Critical materials in crisis The supply of critical materials such as face masks, ventilators and testing was (and remains) crucial during the pandemic. The presence of these critical materials (timeliness, quality and quantity) turned out to be a bottleneck for healthcare capacity. Different countries have dealt with this differently and are now using different strategies for the 2nd wave and a new pandemic. Examples include building a national manufacturing industry and building up iron stocks. The aim of this research is to learn from an international comparison of the different strategies in the Covid-19 crisis. The Dutch approach to material supply is compared with that of 23 other countries. Within the Netherlands, this happens at a national level, but also in various institutions in the cure (hospitals) and care (including nursing homes) sector. The results are expected at the end of 2021.",,2022,PPRC BV,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Other secondary impacts,2020 +P29549,1.043E+13,Migrants on the frontline. The effects of COVID-19 measures on migrant workers working in crucial sectors,"Migrant workers perform essential work in crucial sectors: harvesting, meat processing, packaging, cleaning. During the COVID-19 crisis, they are on the front line and face health risks. Their protection therefore requires urgent attention. An interdisciplinary research team from the Radboud University Network on Migrant Inclusion (RUNOMI), together with De Burcht and partners from the field, will investigate which structural problems surrounding labor migration the corona crisis has exposed and what opportunities this crisis offers to improve the protection of labor migrants. Innovations are also being sought that make crucial sectors less dependent on vulnerable migrants. Because labor migrants often work and live cross-border, this research focuses on the border regions (Netherlands/North Rhine-Westphalia). The research contributes to reducing health risks during the further course of this and any future crises.",,2022,Radboud Universiteit Nijmegen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29550,1.043E+13,Ethics of e-Health during the corona crisis and beyond: lessons from the pandemic,"Ethics of e-Health during the corona crisis and beyond: lessons from the pandemic Due to the COVID-19 pandemic, prevention and (long-term) care now often have to be provided remotely. Healthcare providers use various e-Health applications. Consider, for example, consultations via video calling, apps for self-monitoring, detecting infections and virtual visits from loved ones. Many consultations between healthcare providers have also taken place virtually. What is new is that e-Health replaced direct interaction and was not just a supplement to regular care. The aim of this 'natural experiment' is to learn how e-Health can be used in an ethically and legally responsible manner during and after the corona crisis. Read more about ethics and health View the other projects about ethical issues and corona on our website More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2022,Erasmus MC,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Research to inform ethical issues,Research to inform ethical issues related to Public Health Measures,2020 +P29551,1.043E+13,An unexpected false start on the labor market,"The COVID-19 pandemic and the measures taken are hitting the economy. Government measures to limit unemployment are temporary in nature and mainly aimed at preserving existing jobs. Young people who are now entering the labor market or have recently started a flexible job hardly benefit from this. Young people in a vulnerable position, for example because they are ill, are probably hit harder. As a result, inequality of opportunity between groups of young people continues to increase. Based on administrative data, it is mapped out which groups of young people are hit hardest in the labor market by the corona crisis. These young people are then interviewed and working sessions are organized with policy makers, professionals and young people. This provides more insight into the obstacles that young people experience and appropriate interventions to support young people. The knowledge gained is shared in an accessible manner, so that the results can be used in practice.",,2022,SEO Economisch Onderzoek,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29552,1.043E+13,A (care)ethical analysis of the COVID-19 policy choices,"How does government policy continue to care for everyone, even in crisis situations? The government took drastic measures to contain the corona pandemic. That policy was successful, but there is also criticism. Vulnerable groups were given extra treatment, but had little say. Policy considerations were one-sided and had limited ethical substantiation. At the same time, it became clear how important good care is for a fair and resilient society. Goal The aim of this project is to develop a care ethics policy framework that will help deal with future crises in a more inclusive manner. The research explores the impact of the measures on four groups: people with an intellectual disability, the elderly, people in the palliative phase and refugees. Relatives, healthcare providers and policy makers also have their say. Research design In addition to developing a care ethics policy framework, a policy analysis and insights from interest groups are part of this project. Together these are the building blocks for the new policy framework, which will be widely shared. Methodology: semi-structured interviews, focus groups, working conferences, discourse analysis, normative analysis First results Vulnerability, responsibility and necessity as key concepts in government discourse Vulnerability is narrowly understood at the outset of the crisis as related to a person's physical health status. The government is broadening its perspective on vulnerability as the crisis continues. Necessity is prioritized as a factor that drastically limits the government's room for choice. Although the need for taking measures is clearly highlighted, taking specific measures is justified less extensively in government letters. Responsibility is portrayed as shared between government, society and various groups and institutions. A clearer division of specific responsibilities, in which the government defines and communicates its political responsibility more clearly, is desirable. Report of meeting COVID-19 and Vulnerable groups on February 10, 2021 There is a large group of citizens in the public domain who are hit hard by the consequences of COVID-19 due to their vulnerable position. What are the needs of these vulnerable citizens? During the meeting on February 10, 2021, researchers showed what is going on and what we can do to address bottlenecks and meet needs. View the report of the meeting: Vulnerable citizens during the corona pandemic . Executive parties University of Humanistics, Doctors of the World, Pharos, PZNL, Relief, Tao of Care More information",,2022,Universiteit voor Humanistiek,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons | Internally Displaced and Migrants | Vulnerable populations unspecified | Other,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Policy research and interventions,2020 +P29553,1.043E+13,COVID-19 impact on hospital staff welfare. What are the short- and long-term effects of COVID-19 on the psychosocial and emotional well-being of hospital staff and how do we deal with them?,"Due to the corona crisis, the workload of hospital staff has increased significantly. In this project we map (a) how the mental health and employability of hospital staff changes as the corona crisis continues and (b) which factors determine whether an employee emerges from the crisis better (or worse). We then make targeted improvement proposals that we implement in a hospital in North Brabant and the results of which we communicate widely with all Dutch hospitals.",,2022,Rijksuniversiteit Groningen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29554,1.043E+13,The social impact of COVID-19,"Social impact of COVID-19 monitored over time. COVID-19 has a major impact on various aspects of living together: work and income, well-being, solidarity, neighborhood relations and trust in institutions. Some groups and areas are hit harder than others. An interdisciplinary research team led by Godfried Engbersen (Eramus University Rotterdam) is monitoring the impact of COVID-19 over time. This project was made possible by ZonMw. Goal The project investigates the impact of corona on living together: well-being, solidarity, neighborhood relations and trust in institutions. Research design The project examines the above aspects in relation to each other, with special attention to social inequality. This is done with large-scale survey research, both nationally and in cities and regions. In-depth qualitative research is also conducted. Action strategies are developed together with policy makers, professionals and citizens to increase individual and social resilience. Results The results can be found in podcasts and publications. Executive parties This page lists the collaborating partners. More information",,2022,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29555,1.043E+13,"Mobility during and after corona lock-down: sustainability, safety, inclusivity","The COVID-19 crisis is creating major challenges in many different areas of society. A very urgent one concerns the mobility system. The mobility consequences and challenges of lock-down and relaxation are unprecedented. At the same time, sustainability and accessibility are unchanged social objectives. The MOCOLODO project (MObility during and after COrona LOck-DOwn: sustainability, safety, inclusion) looks at: The effects of lock-down and relaxation on the spatial and mobility behavior of different groups and on the functioning of transport systems The implications for an effective, efficient and fair design of relaxation of corona measures and possible new tightening How to align this with long-term objectives in the areas of sustainability, energy transition and accessibility.",,2022,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Policy research and interventions | Other secondary impacts,2020 +P29556,1.043E+13,Long-term mental health trajectories in recovered Covid-19 patients: exploring the interplay of psychosocial and biological factors affecting health-related quality of life,"Mental health and quality of life of coronavirus patients: the influence of psychosocial and biomedical factors on long-term recovery. This project will investigate: How the mental health and quality of life of coronavirus patients develops in the longer term Which psychological, social and biomedical factors and their possible interactions influence long-term recovery Which individuals are at increased risk for persistent or recurrently impaired mental health and quality of life with the aim of developing strategies for early detection and referral to appropriate interventions This will be investigated within the newly formed RECoVERED cohort of recovered COVID-19 patients, half of whose participants experienced a serious infection requiring hospital admission, and the other half experienced a mild infection at home.",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Post acute and long term health consequences,2020 +P29557,1.043E+13,How can self-employed people and SMEs remain healthy and financially resilient during and after the COVID-19 crisis?,"Self-employed persons and SMEs are hit hard by the COVID-19 crisis, because they have often had to change or end their work. This project investigates what these groups can do themselves to create opportunities to keep their company financially healthy and at the same time remain (mentally) healthy themselves. The effects of specific strategies that are needed to survive the crisis are examined, such as mobilizing external resources (social support, network) and internal resources (self-insight, energy, creativity). In addition, it is investigated whether self-employed persons and SMEs can be supported in the effective application of these strategies through a training intervention. The results are translated into an online training tool that is offered to the target group through their professional and interest associations and an employment agency. The research is carried out in collaboration with the Knowledge Center for Psychology and Economic Behavior.",,2023,Technische Universiteit Eindhoven,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29558,1.043E+13,"Stay home, stay safe? Research into the extent, nature and severity of domestic violence during the Corona crisis","The measures during the corona crisis such as working from home, staying at home and the closure of schools have increased the social isolation of families. As tensions rise in families, the risk of violence also increases. Contact between victims and care providers was made more difficult by the measures, which may have caused domestic violence registrations to lag behind. A delayed increase in reports is therefore conceivable. In this project, systematic research is being conducted into the number, nature and severity of domestic violence reports during the COVID-19 measures compared to last year. Scaling up and down of measures, but also developments in the field are taken into account: changes in the reporting code for domestic violence, corona-related domestic violence campaigns and the code word at pharmacies. Registrations and file data from Veilig Thuis, CBS data and interviews with victims are used. The end result is a monitor that provides adequate information to policy and assistance.",,2023,Nederlands Studiecentrum Criminaliteit en Rechtshandhaving,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29559,1.043E+13,A virus-free high-throughput platform for studying coronavirus replication inhibitors,"The current COVID-19 crisis shows that we are not well prepared for the outbreak of new pandemic viruses. Vaccine development takes a lot of time and that is why antiviral drugs are our best defense against new viruses. Especially if they are able to inhibit a broad group of viruses. The current COVID-19 antiviral 'screens' require experiments with live viruses in a so-called BSL3 facility. Research Within this project, a screening method is proposed to test and optimize COVID-19 inhibitors that can be used in any laboratory. The platform is primarily used to screen new or improved drug candidates. In addition, the platform is used to investigate how COVID-19 activates the innate immune system. This process plays an important role in the course of the disease.",,2023,Amsterdam UMC Locatie AMC,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation",Immunity | Pre-clinical studies,2020 +P29560,1.043E+13,EXCEPTIUS Exceptional powers in time of Sars-CoV-2 crisis,"Although public support for emergency measures was initially strong, it has eroded. Across Europe, citizens are increasingly critical of the democratic costs of containing COVID-19. Moreover, exceptional measures can have a lasting effect on democratic governance. If left unchecked, this decline in public trust could reduce citizens' compliance with public health measures and threaten the stability of democracy. This requires urgent research into the modalities, effects and determinants of emergency decisions in times of crisis. To meet this need, EXCEPTIUS analyzes exceptional decision-making in 32 European countries. The project contributes to the study of democratic resilience by examining why some democratic systems are more resilient to crises and which political reforms increase that resilience. More information about this project can be found on the EXCEPTIUS website .",,2022,Rijksuniversiteit Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Policy research and interventions,2020 +P29561,1.043E+13,"Establishment and duration of protective immunity against SARS-CoV-2, in relation to severity of SARS-CoV-2 infection.","In most people, a specific immune response can be demonstrated after a COVID-19 infection. But it is not known how long and how well this immune response protects against reinfection. This can be investigated at Sanquin because blood is regularly taken from 300,000 blood donors, some of which is also stored for two years. Research The course of COVID-19 antibodies in the serum and (in a subgroup) the memory cells of donors who have had COVID-19 disease - from asymptomatic to seriously ill - will be analyzed for two years. The extent to which an immune response protects against re-infection is being prospectively investigated in 2000 antibody-positive donors. In addition, all people who test COVID19-PCR positive from September 2020 onwards will be checked whether they are blood donors. The plasma from these people that was frozen around July 2020 will then be tested. Expected outcomes If a previous infection is protective, it is expected that there will be much fewer anti-COVID-19 antibodies in the COVID-19 PCR positive group than in the control group.",,2023,Sanquin Bloedbank,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2020 +P29562,1.043E+13,BTK inhibition as therapy for hyper-inflammatory syndrome in COVID-19 patients.,"About 5% of all COVID-19 patients become seriously ill and require intensive care. This patient group often develops serious organ damage and has a high risk of death. This is because certain cells of the immune system, especially the monocytes, react too strongly to the virus. This is also called hyper-inflammatory syndrome. The protein Bruton's tyrosine kinase (BTK) is involved, among other things, in monocyte activation and can be inhibited by the specific BTK inhibitor acalabrutinib. Other cells that are very important for killing the virus, such as T cells, are not affected by BTK inhibitors. Research and expected outcome This study will investigate whether treatment with acalabrutinib indeed leads to clinical improvement in hospitalized COVID-19 patients. In addition, the effects of acalabrutinib on the various cells of the immune system are identified in order to gain knowledge about the mechanism of action of acalabrutinib in COVID-19 patients.",,2020,Erasmus MC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Therapeutics research, development and implementation | Pathogen: natural history, transmission and diagnostics",Prophylactic use of treatments | Immunity,2020 +P29563,1.043E+13,Identification of COVID-19 patients with high Risk of mortality at ICU admiSsion - IRIS-study,"Deciding which COVID-19 patients benefit most from treatment in the intensive care unit (ICU) is an important social issue. New COVID-19 patients are admitted every day. Care for non-COVID-19 patients must also continue. The pressure on ICU capacity became very high during the COVID-19 peak in the spring of 2020, and this could repeat itself in the next wave. Research and expected outcomes This study examines patient characteristics that indicate an extremely long ICU stay or a very high risk of death for the patient. Intensivists, other specialists, the patient and relatives can use this knowledge to jointly make an informed decision about the usefulness of an ICU admission. The research uses three data registers (NICE Foundation , CovidPredict and Vektis ). Together, the registers include all ICU patients in the Netherlands, including detailed and long-term outcome information of COVID-19 patients. Analyzes are done using statistical and machine learning techniques.",,2022,Amsterdam UMC - locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity,2020 +P29564,1.043E+13,Understanding the two faces of the COVID-19 immune response to predict clinical course and define strategies for early and late phase intervention,"The immune system plays a striking dual role in COVID-19. An effective immune response ensures that the virus is attacked and cleared, but if this does not work properly, hyper-activation of the immune system appears to occur, which can lead to serious problems. It is unclear what exactly goes wrong in the immune system in patients with a serious course and how they can best be treated. The use of immune-suppressing medications is one possible strategy. Research and expected outcomes In this study, a collaboration between the UMCU, RIVM and VUmc, a model is developed of the underlying immune response in different phases of COVID by measuring functional cellular defense and circulating protein profiles of patients of different ages and with a variation in disease severity. -19. In addition, predictive biomarkers will be identified and validated that provide insight into optimal timing for specific treatments.",,2024,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Disease models | Immunity | Prognostic factors for disease severity,2020 +P29565,1.043E+13,RAS inhibition to prevent Acute Respiratory Distress Syndrome (ARDS) in patients admitted with a COVID-19 infection,"The COVID-19 pandemic causes high morbidity and mortality because COVID-19 infection can cause acute lung damage and be complicated with severe acute respiratory distress syndrome (ARDS). The renin-angiotensin system (RAS), a well-known cardiovascular cascade, also appears to play a role in the development of ARDS. The COVID-19 virus is believed to consume the enzyme ACE2. This is an enzyme that normally breaks down angiotensin-II (ANG-II). Reduction of ACE2 can cause an accumulation of ANG-II, which can lead to acute lung damage, resulting in ICU admissions and possible death. Research The hypothesis is that RAS inhibition using ACE inhibitors and angiotensin receptor blockers, such as lisinopril and valsartan respectively, can prevent the development of acute lung damage and ARDS in hospitalized COVID-19 patients, thereby preventing ICU admissions and deaths.",,2023,Netherlands Heart Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2020 +P29566,1.043E+13,COVID-19 and ischemic stroke - How to tame a dozing monster,"Patients with COVID-19 pneumonia, especially if they are admitted to intensive care, can develop thrombotic complications, which can contribute to a more serious course of COVID-19 pneumonia. Pulmonary embolism (clot in the lung) is the most common complication, but cerebral infarctions can also occur. The hypothesis in this study is that these strokes may be caused by clotting activation and vessel wall inflammation, or that they are the result of a blood clot that travels from the leg or pelvic vessels through an open connection between the right and left sides of the heart into the cerebral vessels. ends up. Research and expected outcomes In three work packages, knowledge is obtained about: an accurate estimate of the occurrence of cerebral infarctions in COVID-19 ICU patients. the causes and consequences of cerebral infarctions based on imaging studies and laboratory determinations. the optimal prevention of cerebral infarctions by examining the effect of different treatments.",,2024,Leids Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Disease pathogenesis,2020 +P29567,1.043E+13,COVID Data Initiative (INCODA),"Within the project, a dataset has been built of almost all residents of the Netherlands, linked to the GGD test results and COVID-19 related hospital and ICU admissions and deaths. This combined dataset was then used to examine both the risk of infection and the risk of hospital admission, ICU admission and/or death. All results show that socio-demographic factors, such as income, age and migration background, strongly influence both the risk of a SARS-Cov-2 infection and the risk of a serious course of COVID-19. It also becomes clear that it may differ per city or safety region which group has the highest risk of infection. There is a dashboard with the available (anonymous) data developed which makes it possible for everyone to get a detailed picture of which groups tested where and at what time, tested positive for the coronavirus, who was in hospital and who died as a result of the virus. The objectives of INCODA are: 1. Identify groups at high risk for a COVID-19 infection with a serious course 2. Investigate whether the combination of medical characteristics and clinical parameters with geographical, demographic and socio-economic characteristics is valuable and can be used for, among other things, secondary prevention measures and choosing treatment methods INCODA does this by: • combining clinical and ICU admission data of COVID-19 patients with CBS data • identifying risk groups based on a multivariable profile and developing prediction models for the risk of a serious course of COVID-19 • investigating possible interventions",,2022,Amsterdam Health and Technology Institute,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Data Management and Data Sharing,,,,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2020 +P29568,1.043E+13,Consequences and opportunities of COVID-19 for primary schools and their students,"What does the COVID-19 crisis mean for primary school students? What does it mean for their performance and well-being? Are vulnerable groups of students experiencing problems and are there groups of students who have actually benefited? And what do we learn about effective distance learning? This project will answer these questions by mapping the consequences of the COVID19 crisis on primary school students. The project is a unique co-creation of the Education-Lab NL, the National Cohort Research (NCO) of NRO, Maastricht University, the Education Inspectorate, primary schools and the municipality of Amsterdam. With the project we build a bridge between science and educational practice, with the aim of helping vulnerable groups of students. In the coming months, the project will provide toolkits for schools, information about the consequences for students and insight into effective forms of distance learning. You can find these products at www.education-lab.nl, among others .",,2022,Maastricht University,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29569,1.043E+13,"Preconditions for Covid-19 mobile apps: A feature-level investigation of user acceptance based on insights from South Korea and Canada, applied in the Netherlands",How do the Dutch view the potential technologies that can help manage COVID-19? How can opinions about privacy and transparency from other countries be used to enable a safe and efficient app in the Netherlands? This research will show what preferences and opinions people in the Netherlands have about the adoption of COVID-19 apps. The project includes a survey and discussions among stakeholders.,,2021,Tilburg University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2020 +P29570,1.043E+13,Worrying and waving: longitudinal study into the consequences of restrictive measures due to COVID-19 for relatives of people with an intellectual disability and their need for support,"The corona crisis can threaten the health and well-being of loved ones of people with an intellectual disability. At three points during the pandemic, we asked loved ones how they were doing. At the beginning of the corona crisis, loved ones found it harder to care for their family members, because they had to do it more alone and because daytime activities often stopped. Professional care and daytime activities quickly started again. Relatives felt that the corona pandemic lasted a long time and that the measures changed often. That made it difficult to explain to their relatives with disabilities. Mothers and relatives (often parents) with family members living at home have become particularly tired. In order to recover, it is necessary to listen carefully to what they need in order to find solutions together. We expect that more relatives will be thinking about the future care of their family member.",,2022,NIVEL,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29571,1.043E+13,Developing a COVID-19 scoring system for effective and safe triage of patients in primary care,"At the moment, general practitioner care is still split into two: a non-COVID suspect side and a COVID suspect side. We call this process of separation 'triage'. If a patient has complaints consistent with COVID, the patient will be seen in a special room or with special clothing. We have found that too many patients are being triaged as 'COVID suspected', which puts considerable pressure on healthcare. A rapid test at the door of the practice would have been a nice triage tool. However, we have found that a commonly used antigen rapid test is not sufficiently reliable to make such a distinction in the general practitioner setting. We then developed a new triage system based on the patient's symptoms. This is better able to separate patient flows and will hopefully soon be applied in general practice.",,2021,Leiden University Medical Center,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P29572,1.043E+13,"Homeless and Corona, lessons for the future of medical care and shelter","Homeless people are a high-risk group for COVID-19 infection due to a higher chance of exposure to the virus and a greater chance of complications. The preventive behavioral measures are difficult for them and their consequences for their daily lives are significant. The nature and extent of COVID-19-related contacts recorded by street doctors in nine cities show that the homeless population is not more affected than other parts of the population, despite the fact that they relatively often suffer from underlying diseases that increase vulnerability for serious infections. There was a higher percentage of patients who tested positive among homeless people with a migration background. The Corona measures had a major negative impact on homeless people. Mental health deteriorated, with a lot of sadness and anxiety in particular. There was more insecurity such as less income and work and less trust in government and institutions, mainly due to a lack of understandable information. This also applied to vaccinations, although the turnout was reasonable thanks to on-site vaccinations by trusted doctors and nurses in collaboration with the GGD. Interviewed street doctors, civil servants and homeless people experienced the small-scale, 24-hour shelter very positively because of the greater degree of peace for the homeless people. Together with all stakeholders, recommendations have been formulated for pandemic-proof and sustainable shelter and socio-medical care for homeless people. These have been presented to VWS. Results The results have been published in a number of fact sheets. View the results on coronatijden.nl . Executive parties Radboud UMC and Pharos More information",,2022,Radboudumc,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Physicians | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29573,1.043E+13,"Consequences of restrictive measures due to COVID-19 outbreak on loneliness and social needs of residents, loved ones and volunteers in nursing homes","In this study, residents, loved ones and volunteers of nursing homes shared their experiences with the corona measures regarding loneliness, social needs and resilience. Many residents, loved ones and volunteers found it a difficult period. There were often no activities in nursing homes and there was little contact with fellow residents. Social contact was sought in other ways, such as window visits, but this could not prevent loneliness. Residents, loved ones and volunteers mentioned various feelings, such as sadness, fear and powerlessness. But there was also resilience on display. Residents, loved ones and volunteers had varying views on the measures. Safety and protecting residents is important, but the human touch and personal wishes should not be forgotten. Together with healthcare practice and education, the Talking Plate: ""About living with corona"" was developed to look back on and learn from the corona pandemic. This project is a collaboration between the Academic Workshop for the Elderly, Tranzo, Tilburg University, UNO-UMCG and HIVA-KU Leuven. Results Talking plate: About living with corona Based on the research, a Talking Plate has been developed about life with corona. This Talking Plate serves as a means to allow these different groups to talk to each other. With the discussion board, residents, their loved ones and volunteers can look back (with each other) on the corona pandemic and learn from it. More about the results of this research? View all updates here . Executive parties Academic networks for elderly care in Tilburg, Groningen and Leuven. A sounding board group with representatives of the elderly, relatives and volunteers actively contribute ideas during the research.",,2022,Tilburg University,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29574,1.043E+13,Immunity against SARS-CoV-2 in immune-suppressed patients: increased risk of insufficient immunological memory or sufficient protection against re-infection?,"Patients with autoimmune diseases often use immunosuppressive medication. The effect of these treatments on the development and maintenance of adequate immunity after a COVID-19 infection and on the upcoming vaccines against Covid-19 is unknown. Research and expected outcomes First, COVID-19-specific immunity is investigated in patients and healthy people after a COVID-19 infection. In the second phase, the response to a COVID-19 vaccination between infected patients and healthy people is compared. In addition, this response is compared with patients and healthy people without a previous COVID-19 infection. With these results, the hope is to determine the effect of different types of immunosuppressive medication on immunity against COVID-19, so that advice can be given on the optimal vaccination strategy for the many patients with immunosuppression. This study is a collaboration between several university centers, Sanquin Blood Supply and the RIVM (Target to B consortium, T2B).",,2023,Amsterdam UMC - locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +P29575,1.043E+13,"Clinical prediction models for COVID-19: development, international validation and use","For good care of COVID-19 patients, it is crucial to be able to estimate the expected course of their disease. For example: What is the probability that a patient will require intensive care (ICU)? What is the chance of death? Research In this study, a prediction model (https://mdmerasmusmc.shinyapps.io/COPE/ ) has been developed that provides answers to these questions upon admission to hospital. Data from almost 6,000 patients from four Dutch hospitals were used for this. Six easily measurable predictive factors have been used in the models, so that the model is easy to use. The model provided accurate predictions for more than 3,000 Dutch and 2,000 American patients in the second wave of the pandemic. Results Interviews with healthcare providers, patients and relatives showed that they see the value of these types of models when making decisions about optimal care for the patient. The models must then be available electronically and the predictions must be clearly communicated. View the scientific publication with the results of this research.",,2021,Erasmus MC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity,2020 +P29577,838002524,E-Health Coach Autismepunt,"Autism Point is a healthcare organization specialized in providing assistance to people with autism. Autism Point offers outpatient care in the areas of guidance, diagnostics and treatment, housing, social activation, job coaching and reintegration. All this is aimed at ensuring that people with autism can function as independently and meaningfully as possible. The problem Due to the COVID-19 situation, the need for eHealth support in the right form has accelerated. Within our client group there is a need for the use of different types of digital support. Digitization is increasingly part of healthcare, now and in the long term. In addition to improving care, we want to bridge the (too long) waiting time between intake and the start of guidance/treatment. Request for help We need support in making the right choice to digitize, then in setting up all forms of care that we offer, especially for clients with autism.",,2021,Autismepunt BV,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29578,638010079,District official confused behavior Hengelo,"Goal The municipality of Hengelo, healthcare organizations and the police will work together to provide confused people with help sooner. It is becoming increasingly common for people with confused behavior to cause nuisance. These people are often already known in the neighborhood, to the police or organizations. By deploying the 'District Officer for Confusional Behavior', the municipality of Hengelo wants to prevent someone from falling into crisis by providing appropriate support sooner. Method The Wijkracht and Ixta Noa district officials will visit these people from September 1, 2020. They get to know each other and ask how someone is doing. They try to do what is necessary to prevent a crisis situation by making contact with people in the area. The district official also has contact with people who have been confused in the past, so that a possible relapse can be prevented. The District Officers are active in the Klein Driene and Hengelose Es Noord districts. Results An experienced employee from IxtaNoa and an experienced social worker from Wijkracht have set out together to support people who have concerns in the Hengelose Es-Noord and Klein Driene district. Assisted by colleagues from intervention care (Mediant and Tactus), they managed to help a large number of local residents, despite Covid. The local police officer and housing association Welbions in particular were very satisfied with the great expertise and the opportunity to work together smoothly and in a targeted manner. Local residents were satisfied with the commitment offered both online and at an appropriate distance due to all Covid restrictions. After the project, the collaboration will be further developed: both organizations remain involved in the further development of a neighborhood location so that local residents have a nice place in the neighborhood where they can go with their questions, but also for relaxation and to meet others.",,2021,Gemeente Hengelo,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29579,1.043E+13,Healthcare use in primary care during the corona pandemic: a national population study from the perspective of the patient and the healthcare provider,"Our research shows that 1 in 5 people with complaints avoided care during the first lockdown of the corona pandemic. This often concerned vulnerable people with immediate complaints such as chest pain, paralysis of an arm or leg or complaints that made people think they were cancer. These people may have been seen by a healthcare provider later or not at all. This raises the question of whether avoidance of care has led to damage to health. We show that this was indeed the case. A third of all people with a Transient Ischemic Attack (TIA) or stroke did not contact a doctor in that first lockdown, while people with a heart attack did find their way to care. We conclude from this that access to care has changed during the pandemic. People mainly sought less help for complaints that they find difficult to explain, such as those of a stroke. This research underlines the importance of accessible care, even during a pandemic. In particular, attention should be paid to better recognition of the symptoms of a stroke. Background During the COVID-19 pandemic, people have started avoiding healthcare. In addition, the healthcare capacity has changed due to the measures. Decreases in the use of (regular) primary care can lead to damage to health, for example due to late-diagnosed or untreated cardiovascular diseases or oncological conditions Vlog and blog In the vlog below, the researchers tell more about their research. They also tell more about this special research in this blog.",,2022,Erasmus MC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29580,1.043E+13,Impact of COVID-19 on children and young people with autism spectrum disorder (ASD) and their families,"The Rotterdam Autism Consortium (R.A.C.; collaboration Erasmus University Rotterdam, Youz, Yulius, and Erasmus MC-Sophia) investigated in a mixed-method longitudinal research design what 1) the psycho-emotional impact, 2) risk and protective factors, and 3) care and information needs during the COVID-19 pandemic. Outcomes were compared with control data from Generation R, a general population cohort. It has been found in more than 50 families that young people with ASD experience the impact of the pandemic, but that this is similar to neuro-typical young people and with ""regular maturation"". However, there is greater variation in the ASD group, which has important clinical implications. For parents, severe role restriction and mild problems in the parent-child relationship, physical health and overall burden are the main concerns during the lockdown. Many parents indicate that they have just made it and are under maximum strain. Changes in policy and information increase this burden. Concerns about future problems resulting from the pandemic are also mentioned. Webinars The project has produced 2 webinars: 1. Autism & COVID-19 2. Impact of the COVID-19 pandemic on families with children with autism spectrum disorders Executive parties Erasmus University Rotterdam, Yulius, Sophia Children's Hospital, Parnassia Group",,2022,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29581,1.043E+13,TRACE II: Outcome in patients undergoing postponed elective surgery during the COVID-19 pandemic,"Background During the corona crisis, many planned operations were postponed and waiting times increased. This project investigated whether postponing operations has consequences for health and recovery. In 7 different hospitals, patients were asked to complete questionnaires and medical information was collected about their recovery after surgery. These data were compared to a control group from a similar 2019 study (TRACE I). First results: Patients with a delayed operation were less fit just before the operation and had a lower quality of life than the control group. After the operation, the number of patients with a serious problem or death was the same as the control group. However, the quality of life remained lower up to 30 days after the operation. The results of this study may help in future planning of surgical care in the event of a crisis situation.",,2023,Maastricht University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Controlled Clinical Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29582,1.043E+13,"COVID-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: a combined rehabilitation, pulmonary, and intensive care perspective (CO-FLOW study)","After hospital discharge, COVID-19 patients follow different aftercare pathways, such as in a rehabilitation center, nursing home or physiotherapy practice. Little is known about the eventual recovery after COVID-19 and the effect of these aftercare pathways. Background The COVID-19 pandemic has forced a rapid development of aftercare for hospitalized COVID-19 patients. Whether this aftercare provides the right care in the right place for patients who experience long-term complaints after COVID-19 is unknown. Goal Mapping the long-term consequences of COVID-19 in patients who have been hospitalized and further developing aftercare pathways. Research design COVID-19 patients who have been hospitalized in the Rotterdam-Rijnmond and Delft region will be followed for 2 years. Data is collected about patient flows in the various aftercare pathways, care use, facilitating and hindering factors in the aftercare process as experienced by healthcare professionals and patients, (work) participation, quality of life and (predictors of) physical, cognitive and psychological recovery. Measurements are taken at 3, 6, 12 and 24 months after hospital discharge. The first results It is expected that patients who have had COVID-19 may continue to experience complaints in various areas for a long time after hospital discharge. The research provides insight into the long-term consequences of COVID-19 and makes aftercare better tailored to the patient. 650 patients are participating in the study. Interim analyzes show that despite often good recovery from lung damage and lung function, 51% of patients are still tired six months after hospital discharge, which has an impact on the quality of life. These results can be read in the articles below. Persistent health problems beyond pulmonary recovery up to 6 months after hospitalization for SARS-CoV-2 CO-FLOW: COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: study protocol of a multicenter prospective cohort study following patients 2 years after hospital discharge",,2024,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P29583,1.043E+13,Changes in the use and organization of care in general practices and out-of-hours services: lessons learned from the COVID-19 pandemic,"The outbreak of the COVID-19 pandemic had a major impact on care provided by the GP or the GP post. In the COVID-GP project, we investigated the consequences for healthcare use and the organization of GP care using 1) data from the electronic patient records of the GP or GP post, 2) questionnaires from the Nivel Corona cohort and 3) interviews with patients and healthcare professionals. In the first phase of the pandemic, there was a significant decrease in care provided by the GP and some care was provided remotely. Despite positive experiences with accessibility (longer consultations, less crowds in the waiting room) and effectiveness (limiting patient flows through triage (medical and non-medical rules that teams of healthcare providers must follow when making such a choice, this is called ""triage"") and remote care), healthcare use increased again over time/the pandemic and consultations were more often scheduled in the GP practice again. More research is needed to find out what the long-term effects are of postponed or missed GP care and how the solutions in the pandemic can also contribute to reducing the pressure on GP care outside a pandemic. Objective The overarching goal of the project is to gain insight into the impact of COVID-19 measures on healthcare use and organisation of care in GP practices and HAP and the experiences of patients and professionals. Research design The research is a collaboration between Nivel and the UMCG. Routine care data from the electronic patient files of GP practices and HAP are analysed to map healthcare use. These will be related, with specific attention to vulnerable groups in our society, to: Organisational changes Experiences of patients and healthcare professionals obtained from interviews Questionnaires and data on the use of Thuisarts.nl First results The first results of this research can be found published in March 2021. This concerns reduced healthcare use in 2020 for non-COVID-19 associated care, except for the elderly. These are the key points of the article: During spring and autumn, healthcare use at the GP post for non-COVID-19 associated health problems was significantly lower, compared to before the corona pandemic. In the summer, healthcare use was comparable to 2019. Among the elderly (≥70 years), there was no decrease in healthcare use at the GP post for non-COVID-19 associated health problems during the corona period of 2020. There was an increase in contacts with the GP post related to (inspections at) death/death and dyspnea/shortness of breath attributed to the airways for the elderly (≥70 years). The article can be read on the Nivel website. Furthermore, a quarterly report has been made on decreased healthcare use by pregnant women and women who have just given birth. A report on healthcare use among COPD and asthma patients will follow soon.",,2023,Nivel,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29584,1.043E+13,The impact of the COVID-19 outbreak on the diagnosis and treatment of cancer patients: lessons for the future.,"The corona crisis has influenced the diagnostic process for cancer. Patients avoided their GP, especially during the first wave, even in the case of so-called 'alarm symptoms' for cancer. In addition, corona caused delays in the recognition and referral of colon and lung cancer patients to the GP. Whether this had an influence on the course of the disease is still unknown. Particularly in the first wave, the incidence (how many new cases of disease there are in a certain period) of cancer patients decreased, but this has largely been overtaken later. Furthermore, changes have taken place in the diagnostics and treatments carried out in the hospital process, but the impact of these is limited. In addition, the lead time to start of treatment for most patients was shorter during the corona crisis than in previous years. The most important lessons for the future are that guidelines can be implemented quickly and there are options for physical and online consultations in the future, where coordination with the patient is important. Goal 'Lessons for the future' are formulated to ensure an optimal balance between adjustments in care required by COVID-19 and the quality/availability of care for people with cancer. Background The detection and care of patients with cancer may have been different and less successful during the COVID-19 outbreak. Research design To prevent the next outbreak or similar major health crises, the following questions are answered: How big was the impact of the COVID-19 outbreak on cancer detection? Why were cancer diagnoses delayed and how can we prevent that? How has healthcare been adapted and what effect does this have on the quality of care? How can this be better next time? First results The results of this project can support healthcare content, organizational and financing decisions in healthcare in the short and long term. The results are important for society and the future patient, because avoidance of care and loss of health must be prevented. The first results are in a fact sheet In summary. On the website of the Integrated Cancer Center Netherlands there are other results.",,2023,Integraal Kankercentrum Nederland,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29585,1.043E+13,Effects of Covid-19 on GP visits by patients in deprived areas,"General practices in deprived neighborhoods have provided more care remotely during COVID-19: telephone advice, e-mail, video calling, e-health. The consequences of Covid-19 for general practitioner care for vulnerable groups in deprived neighborhoods were examined. After the COVID-19 outbreak, there was a significant decrease in consultations in the first months. After the first year, healthcare use in general practices in deprived neighborhoods has largely recovered, but consultations for COPD are lagging behind. GPs find remote care less suitable for patients with few language and digital skills and the elderly. It is important for patients in disadvantaged neighborhoods that there is good access to general practitioner care in times of crisis. Remote care can be provided to patients who are able and willing to do so, but only if there is a good relationship of trust with the GP. Goal This research should make it clear for which groups remote care is suitable and where space is created for patients who need more care. To this end, experiences with the changing way of working are mapped out Research design The research is divided into different phases, making it possible to use interim insights in the event of a resurgence of the virus. General practitioners are actively involved in the research, so that the knowledge gained can be applied immediately. General practices participate in interviews and keep diaries. They also register the use of the GP by patients. General practitioners and GP practice assistants (POHs) from 15 general practices in deprived neighborhoods were interviewed twice: in the first phase of the corona crisis in 2020 and in the spring of 2021. First results In the first phase of the corona crisis in 2020, 90% of patient contacts were remote: mainly by telephone, but also (to a lesser extent) video calling or email. In the spring of 2021, general practitioners often estimate the ratio of face-to-face and remote care to be approximately 50%-50% or 2/3 vs. 1/3 (with peaks of 80%-20% and 40%-60 %). In the first phase in 2020, POHs often provided remote care, mainly by telephone. In the spring of 2021, the GP practice assistants returned to mostly face-to-face consultations. Face-to-face consultation versus remote care General practitioners are predominantly more positive about remote care, due to (successful) experiences and enthusiasm of patients. But many general practitioners still find remote care less suitable for residents with less language skills or with low education. Many practice nurses find face-to-face contacts a better way to provide care, because they can also better observe the patient's non-verbal communication. POHs find the flexibility positive if care is possible remotely in some cases. The analysis of data from GP information systems is being prepared and the effect of the degree of remote care on healthcare outcomes is being investigated. The research results are regularly presented during interactive online meetings with stakeholders. For more information, see this fact sheet , report about remote care and the project page on a website with research projects on the theme of vulnerable groups and COVID-19.",,2023,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29586,1.043E+13,CONTROL: effectiveness & optimization of source and contact research to limit the spread of SARS-CoV-2,"Source and contact research (BCO) is of great importance to limit the spread of the coronavirus (SARS-CoV-2). In order to investigate and improve the effectiveness of BCO, seven GGDs (Amsterdam, South Limburg, Rotterdam-Rijnmond, Groningen, Flevoland, Hart voor Brabant, Regio Utrecht) and the RIVM-CIb are starting a joint scientific project: CONTROL. CONTROL will evaluate the process and effectiveness of the BCO. It will examine which characteristics of people with the coronavirus and their contacts determine the lead time and effectiveness of the BCO. Barriers and success factors for the BCO will be identified in consultation with field parties and an improvement plan will be drawn up. It will also investigate which factors are predictive of further virus spread. In addition, a tool will be developed to perform BCO quickly and intensively for people with the coronavirus who could potentially infect many others. On January 28, 2022, the paper ""Self-reported symptoms as predictors of SARS-CoV-2 infection in the general population living in the Amsterdam region, the Netherlands."" published.",,2023,GGD Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P29587,1.043E+13,"Improvise, adapt, overwork? Understanding and learning from hospitals'''' adaptations to COVID-19 and their effects on professional functioning and recovery.","In this project we investigated how hospitals respond to the rapid changes brought about by the COVID-19 pandemic. We have found a number of ways that help hospitals to better recognize developments, act on them more effectively and learn from these adjustments. The results also show that for some healthcare professionals the efforts required of them and the reward and appreciation they receive in return are not in balance. As a result, employees feel less and less committed to their work and some regularly think about leaving healthcare. By offering a good social team climate, reducing emotional burden as much as possible, providing clarity about working conditions, offering development opportunities, and allowing employees to contribute something valuable at work, hospitals can protect the well-being and employability of their staff. First results Based on the first round of questionnaire data is a scientific article published about this research. The article shows that both personal resilience of hospital staff and the social team climate have a positive influence on employee well-being during the COVID pandemic. Employees who have a higher degree of resilience are less concerned about COVID infections and also have fewer symptoms of depression. Employees who work in a team in which they experience a good social climate also have fewer depressive complaints. A good social team climate also forms a buffer against depressive complaints for employees who are concerned about infections. The complete catalog of adjustments hospitals are making during the COVID pandemic and the lessons they learned from it is available.",,2022,Maastricht University,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Hospital personnel,Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Social impacts | Health workforce,2020 +P29588,1.043E+13,Integrative analysis of multi-omics longitudinal data to identify effective strategies for the prediction and treatment of COVID-19,"Some COVID-19 patients develop very severe respiratory symptoms, while others experience mild flu-like symptoms. Although it is clear that genetic and non-genetic factors influence the severity of the disease course, the underlying molecular mechanisms are unknown. As a result, the course of the disease for an individual cannot currently be predicted. Research and expected outcomes This project aims to gain more insight into the disease and predict its progression by using long-term measurements of multi-omics data. With the ultimate goal of developing a treatment strategy for individual patients.",,2023,Radboud Universitair Medisch Centrum,,Unspecified,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis,2020 +P29589,1.043E+13,Altered IgG fucosylation driving pathologies in COVID-19: Relevance for diagnosis and therapeutics,"People who become infected with COVID-19 have very diverse reactions. Some people don't notice anything, others show mild complaints and some become seriously ill. Typically, people with complaints either recover or experience a worsening of complaints after about a week after infection. This is accompanied by the activation of the adaptive immune system, which is then able to clear the virus. Unfortunately, this immune activation appears to be too intense in some patients. The cause of this is unclear. Research and expected outcomes Research indicates that an important functional switch in antibodies - the sugar fucose - is 'on' in some viral infections, including in seriously ill COVID-19 patients, and not in people with mild complaints. In this project, the development of this type of response and the influence on antibody (plasma) therapies in patients is studied. The results will hopefully lead to more efficient and safer use of antibody-based therapies.",,2023,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Prognostic factors for disease severity | Disease pathogenesis,2020 +P29590,1.043E+13,ReCOVer: A Randomised Controlled Trial testing the efficacy of Cognitive Behavioural Therapy for preventing chronic post-infectious fatigue among patients diagnosed with COVID-19,"Some of the patients who have experienced COVID-19 continue to have complaints. One of those complaints is fatigue. This is often serious and limits people's functioning. Cognitive behavioral therapy can help with severe fatigue that arises during an illness. Behavioral therapy teaches people to deal with complaints differently. Goal By comparing both groups, it is examined whether behavioral therapy leads to a decrease in fatigue and limitations, and whether fewer people become chronically tired after COVID-19. Research design This project examines whether behavioral therapy given via the internet also helps with fatigue after COVID-19. By treating the condition sooner after the onset of the complaint, the fatigue will hopefully be prevented from becoming chronic. 114 patients who are hampered by severe fatigue after COVID-19 are participating. Half receive behavioral therapy, the other half receive usual care. Coincidence determines which group a participant ends up in. The treatment lasts four months, with people being examined immediately afterwards and six months after the treatment. Expected results By comparing both groups, it is examined whether behavioral therapy leads to a decrease in fatigue and limitations, and whether fewer people become chronically tired after COVID-19. Executive parties Amsterdam UMC, Catharina Hospital, Radboud UMC, Bernhoven, Jeroen Bosch Hospital.",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P29591,1.043E+13,"A phase-2-study, pivotal for clinical development of lanadelumab for treatment of COVID-19","COVID-19 can lead to fluid in the lungs, causing oxygen deficiency. If this is present for a long time, it can lead to intensive care (IC) admission and ultimately death. There are indications that the virus disrupts the regulation of blood vessel wall permeability because the virus reduces the function of the protein angiotensin converting enzyme 2 (ACE2). As a result, quinines produced can no longer be broken down at the site of the infection. Quinines can make the blood vessel wall permeable to fluid. Research and expected outcomes This study investigates whether inhibiting the production of quinines with the drug lanadelumab can lead to a rapid recovery from oxygen deficiency. The aim of this treatment is to prevent an ICU admission when patients are admitted to hospital and have signs of fluid in the lungs and oxygen deficiency. If there is a clear effect, the strategy to inhibit the quinine system in COVID-19 will be investigated in larger trials.",,2023,Radboud Universitair Medisch Centrum,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Clinical,"Clinical Trial, Phase II",Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Therapeutics research, development and implementation",Clinical trials for disease management | Clinical trial (unspecified trial phase),2020 +P29592,1.043E+13,"The impact of COVID-19 among people with low literacy and people with disabilities: measures, (mental) health and perspectives for action with regard to care and support needs and policy","What do we know thanks to this project? In this project we have provided insight into the consequences of the pandemic on the mental health of people with difficulty with the Dutch language (people with a mild intellectual disability and people with low literacy). We now know that this one is big. In particular, the loss of a daily structure and no longer seeing people you know has a major effect. Our project also shows that our target group needs understandable information. Not being able to properly understand the measures creates unrest and makes it difficult for people to follow them, even though they generally want to do so. Why is this important? At the outbreak of the pandemic, a national effort was made to map out the consequences for citizens. In regular studies, people with difficulty with the Dutch language are not or hardly represented, while there were indications that they could be hit harder. Thanks to this project, we know even better how we can achieve this.",,2023,Radboud Universitair Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29593,1.043E+13,WikiPathways as a platform for COVID-19 biological pathway models,"WikiPathways is a globally known and established knowledge platform, founded and maintained by Maastricht University. The platform makes molecular pathway models accessible to researchers, keeps its pathway collection up-to-date and supports the drug development process for the different phases of COVID-19. Research The research has three aspects to help fight COVID-19 and future outbreaks: Expansion of WikiPathways as a source for COVID-19 pathway models. This is done by sharing models and information and collaborating with all COVID-19 research. Improvement of software to better describe virus-human interactions within relevant COVID-19 molecular processes so that computers can use them. The development of analysis procedures using the constant influx of knowledge, experiments and clinical data.",,2024,Maastricht University,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Health Systems Research,Health information systems,2020 +P29594,1.043E+13,Obesity as an amplifier of inflammation and organ injury in SARS-CoV-2 infected patients: prognostic potential and therapeutic target,"Recent research shows that 77% of COVID-19 patients treated in a Dutch Intensive Care Unit (ICU) were overweight. There is evidence that there is a positive correlation between obesity and the severity of COVID-19. It is not yet known why overweight people often come to the ICU with serious symptoms of COVID-19. Research and outcomes This study investigated the underlying molecular mechanisms behind the enhancing role of excess adipose tissue on the response of the COVID-19 patient. Research has been conducted into exactly how excess fatty tissue contributes to the development of organ failure, especially failing lungs and kidneys. The study found that substances secreted by excess adipose tissue are associated with severe COVID-19 cases, including hospitalization, ventilation and organ support in intensive care. In contrast, there was no direct link with death. Similar changes in these substances were also observed in non-COVID-19 patients. The study also found that SARS-CoV-2 infection causes more organ damage than bacterial infections. Although the virus attacks fatty tissue, the released virus particles have limited ability to re-infect other cells. In addition, the study showed that the dietary supplement resveratrol has a strong and long-lasting antiviral effect on SARS-CoV-2.",,2023,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis,2020 +P29595,1.043E+13,"Towards a population-oriented approach to prevention, care and support by identifying vulnerable groups as a result of the COVID-19 pandemic and control measures","The outbreak of the coronavirus and the measures taken have major consequences for the health of the Dutch population. These health effects are not equally distributed; not all population groups are equally vulnerable to it. Moreover, the health effects are not always clearly visible; Vulnerable groups in particular are often less well represented. There is therefore a risk that this crisis will increase existing health differences in the Netherlands. In this practice-oriented research project, through research into existing data, interviews and group discussions, we have gained insight into 1) which population groups are (extra) vulnerable to the consequences of the corona period; 2) what health effects - physical, mental and social - the corona period had on these groups; 3) which solutions can be used to prevent or combat negative effects, and to increase resilience so that people can better cope with a possible next crisis. We have also learned important lessons about how we can better involve these groups in research. The following objectives were central to this project: Gain insight into which groups are vulnerable to the Corona measures and why Looking for good examples of how to recognize early when vulnerability arises and ways to prevent this. This is done by looking at various neighborhoods in the province of Utrecht to see what good examples already exist and what needs to be newly developed to remain healthy. Ensuring that the knowledge of goals 1 and 2 can also be used in other places, for example in other cities, in other countries and in (care) training. Results This project has published a fact sheet of what makes people vulnerable during the COVID-19 pandemic and what measures can help. Executive parties UMC Utrecht, Municipality of Utrecht, Trimbos Institute, NIVEL, Pharos, Meetellen Utrecht, Al Amal Foundation, GGD Utrecht, Municipality of Zeist",,2023,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts | Social impacts,2020 +P29596,1.043E+13,Online academic education due to COVID-19 crisis: Who does it work (not) for and what factors can explain this?,"As a result of the COVID-19 pandemic, academic education has changed drastically. There has been a transition from face-to-face education to mainly online education. The impact of this transition on student satisfaction, participation, social interactions and performance is still unclear. Online education will be a good fit for some students, but other students may benefit less from this form of education. A longitudinal cohort study will investigate which personal characteristics of students (such as gender and age), as well as psychological characteristics (such as personality and needs) of students play a role in this. For this research, an online questionnaire will be distributed three times to students at Dutch universities during the 2020/2021 academic year. The Intercity Student Consultation and the National Student Union function as collaboration partners.",,2023,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29597,1.043E+13,Vulnerable in Amsterdam: The organization and effects of supporting vulnerable groups during and after the corona crisis,"The most vulnerable people are hit hardest by the COVID-19 pandemic. Many organizations have provided widespread assistance to vulnerable people during the crisis. Choices have been made in this assistance to the vulnerable. Such as: who gets help? How can distance be kept? What online options are there? This often went well, but sometimes there is the feeling that it could be better. In view of a possible second COVID-19 wave, it is very important to investigate the organization of assistance to vulnerable groups in a timely manner and to learn lessons from it. Goal This project aims to provide insight into the consequences of the corona crisis for various vulnerable groups in the Amsterdam region. It examines how assistance has been provided and how assistance can be organized in the medium and long term. Researchers, care providers and experts jointly make an inventory of the knowledge and experiences gained and develop help solutions. Research design Interviews, surveys, observations The first results Mixed image Those hardest hit are those in the process of reintegration Structure (pending), perspective and housing are the biggest problems Reducing negative effect of mental health care (and sometimes general practitioners) Emergency shelter has positive effects on rest and treatment Dilemmas in care, e.g. proximity versus distance E-health applied positively (but also in situations where more difficult) Executive parties Vrije Universiteit Amsterdam, GGD Amsterdam, HVO-Querido, De Regenbooggroep and the Salvation Army Amsterdam More information",,2022,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Indirect health impacts,2020 +P29599,1.043E+13,Identification of the pathogenesis of COVID-19 pathology in the Dutch population and unraveling differences in pathogenetic mechanisms between high- and low-risk groups.,"COVID-19 has a striking variation in disease severity between patients. There is currently insufficient knowledge about which processes in the tissue are the cause of this variation. This limits the development of targeted diagnostics and therapy for individual patients. Studying the tissue of COVID-19 patients can change this, because the tissue can distinguish between damage directly caused by the virus, inflammation that has gotten out of hand, increased clotting, and scarring, all of which may require different treatment. Research and expected outcomes In the context of this project, the available and suitable tissue from both deceased and living COVID-19 patients in the Netherlands is being brought together in order to ask and answer these questions. The results are expected to lead to an improved understanding of the variability of this disease and lead to more personalized treatment.",,2023,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Disease pathogenesis,2020 +P29600,1.04301E+13,Convalescent plasma as a treatment for high-risk outpatients administered within 7 days after COVID-19 disease onset (CoV-Early),"The CoV-Early study examines whether administering plasma from former corona patients leads to a faster recovery in corona patients who have not yet been admitted to hospital. Because previous research in the Netherlands showed no benefit from treatment with plasma at a later stage of the disease (in the hospital), we administer it quickly in this study (at the latest seven days after the onset of the disease). Research In this study, one group of patients receives plasma with antibodies and a second group, the control group, receives plasma without antibodies against the coronavirus. This is necessary to be able to reliably investigate the effectiveness of plasma. To participate, a patient must be at least 70 years old or 50 to 69 years old and also belong to a risk group. The study is coordinated by Erasmus MC and LUMC and was set up in collaboration with Sanquin. More information New corona treatment with blood plasma can start (Nov 2020) New national research into the effectiveness of antibodies in corona patients (Oct 2020) www.covearly.nl More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2022,Erasmus Medisch Centrum,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Clinical characterisation and management,Clinical trials for disease management,2020 +P29601,1.043E+13,SARS-CoV-2 transmission in secondary schools and the influence of indoor environmental conditions,"We quantified pre-vaccination (2020/2021) SARS-CoV2 transmission in secondary education and investigated the association with indoor climate and COVID19 mitigation measures. To this end, we combined environmental and virological measurements in experimental settings and field studies in 18 secondary schools, supplemented with 4 detailed SARS-CoV2 outbreak studies. During a period of low population immunity and limited measures in education, there appeared to be undetected SARS-CoV2 transmission in schools. Furthermore, national government measures aimed at reducing contacts proved effective in reducing the SARS-CoV2 incidence in schools, but an additional positive effect of self-initiated local measures by schools was not found. Adjustments in ventilation practices were made during the study, which somewhat limited the generalizability of the conditions. However, an effect of higher CO2 concentration in classrooms on SARS-CoV2 incidence in schools was not found and there was no evidence for large-scale environmental contamination with SARS-CoV2, even during outbreaks. The combined results suggest a limited role for airborne transmission over longer distances under the conditions prevailing in schools during the study. The research has also contributed to optimization of sampling techniques for virus-containing aerosols and CO2 measurements in classrooms.",,2022,Universitair Medisch Centrum Utrecht,,Human Populations | Viruses | Environment,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,"Disease transmission dynamics | Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures",2020 +P29602,1.043E+13,BCG vaccination to minimise COVID-19 disease severity and duration,"Mycobacterium bovis is the bacterium that causes tuberculosis in cows. The BCG (Bacillus Calmette-Guérin) vaccine consists of weakened bacteria of this strain. Almost 100 years ago it was discovered that BCG protects against human tuberculosis. In recent years it has been shown that BCG also provides protection against other infections by activating the immune system in a broad sense. BCG can therefore potentially also provide protection against COVID-19. Research This study investigates whether BCG can reduce the incidence, severity and/or duration of COVID-19. The impact of BCG on the development and longevity of COVID-19 antibodies, the immune system in a broader sense and the microbiome composition of the respiratory tract is also being investigated. Expected outcomes If BCG is effective, it could be used to protect risk groups until COVID-19-specific vaccines become available. In that case, BCG could also be used in future epidemics caused by new pathogens.",,2022,Universitair Medisch Centrum Utrecht,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Vaccines research, development and implementation","Supportive care, processes of care and management | Characterisation of vaccine-induced immunity",2020 +P29603,1.043E+13,"Measuring, understanding & reducing respiratory droplet spreading","To control the COVID-19 pandemic, it is important to prevent the spread of the deadly coronavirus. The virus spreads through small droplets containing virus particles when talking, coughing, singing, etc. Unfortunately, not much is known about these small droplets. That is why the authorities are now using the 'social distance' rule. Research and expected outcomes The aim of this research is to measure and understand the release and spread of respiratory droplets when someone talks, coughs, sings, shouts and breathes. In addition, it is being investigated to what extent face masks contribute to preventing the spread of respiratory droplets. With the results of this research, the researchers hope to provide answers about the usefulness of wearing face masks and to find good strategies for ventilation.",,2022,Universiteit Twente,,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Infection prevention and control,"Impact/ effectiveness of control measures | Barriers, PPE, environmental, animal and vector control measures",2020 +P29604,838002527,Over the threshold,"About the Threshold During the outbreak of COVID-19, we as a practice tried to offer our clients treatments in the form of e-health solutions. As therapists, we experienced limitations due to our treatment vision from fascia therapy. Our patients also indicated during telephone contacts that ""it went well"" or ""I will come again when that is allowed again"". We then started looking for solutions to help our clients overcome the hurdle that apparently existed when it came to using e-health. We realized that we, as physiotherapists, needed coaching in this regard. We found this in the project ""Over de Drempel"". Through this coaching we also want to ensure that patients at a greater distance from the practice can be helped with our specialization. If you would like to know more about the ""Over de Drempel"" project, please contact: info@fysiodevoorbuiten.nl mark@hcic.nl carolien@fysiotherapieopmaat.nl",,2021,Fysiotherapiepraktijk DeVooruitgang,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29605,838002528,Over the threshold,"As a practice, we tried to offer our clients help through EHealth solutions in the form of video consultations at the outbreak of COVID-19. Our clients saw no added value. That is why we started looking for solutions to help our clients cross the threshold and use EHealth. We do this by means of a call script in which people are informed about the possibilities of EHealth applications in physiotherapy practice. When using this calling script, we receive coaching on how to use the calling script. We are currently in phase 3 of the process, September 29, 2020, and we can start offering EHealth to our clients via the call script. More information about the call script or coaching on this? e.gierman@wijnhoven-gierman.nl carolien@fysiotherapieopmaat.nl mark@hcic.nl",,2021,Fysiotherapie en Manuele Therapie Wijnhoven-Gierman,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29606,1.043E+13,Primary care Research on Outcomes of COVID-19 (PRO-COVID-19),"In the first part of this project, we developed and validated a model based on data from 5636 patients that general practitioners can use to predict which patient with the coronavirus has an increased risk of hospitalization. This is the first model that combines patient complaints with their history and is suitable for use in general practice, the first point of contact for patients when they develop complaints about their infection. It can also be used by policy makers. In the second part of this project we conducted research into the long-term symptoms in patients with a lower respiratory tract infection with and without corona. We found that a significant proportion of patients still have complaints after 12 months, but that this did not differ between patients whose lower respiratory infection was or was not caused by the coronavirus. Long-term complaints after a respiratory infection do not appear to be specific to the coronavirus, but do require further attention in research and the consultation room. More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2022,Universiteit Maastricht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Post acute and long term health consequences,2020 +P29607,1.043E+13,Therapeutic inhibition of excessive lung inflammation induced by anti-SARS-CoV-2 antibodies,"In critically ill COVID-19 patients, pneumonia is accompanied by very strong inflammatory responses, which can lead to multiple organ failure and ultimately death. The current treatment options for seriously ill COVID-19 patients are unfortunately limited. Because the development and distribution of a vaccine will take one to two years, there is an urgent need for a treatment for this category of sickest patients. Research and expected outcomes This study will investigate the underlying reason for these serious inflammatory reactions and will test which possible treatment options (medications) can counteract these extreme inflammatory reactions. The findings indicate that critically ill COVID-19 patients produce a different type of antibodies against the virus, which then causes the extreme inflammatory response. This could explain why this group of patients deteriorates so much after about a week and a half. The first results The results of the research were published in the scientific journal Science Translational Medicine on May 11, 2021. More information about the results can be found in the article by Amsterdam UMC or watch the video .",,2023,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis,2020 +P29608,838002526,About the Threshold,"As a practice, we tried to offer our clients help through e-health solutions in the form of video consultations at the outbreak of COVID-19. Our physiotherapists find this difficult; Which treatment instruments do you use if you can no longer treat hands-on in practice? That is why we started looking for solutions to help our patients cross the threshold and use e-health. We do this through coaching in which physiotherapists are informed about the possibilities of e-health applications in physiotherapy practice. This project is successful if we have implemented video consultations in our care.",,2021,De Fysio BV,,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29609,1.043E+13,Serologic surveillance of SARS-CoV-2 during the 2020 pandemic in exposed and unexposed healthcare workers in a tertiary care hospital in Amsterdam (S3 study),"Within our project, we followed up approximately 800 hospital workers during the COVID-19 pandemic through questionnaires and blood samples. We saw that employees who worked with COVID-19 patients were more likely to become infected with SARS-CoV-2 themselves. Genetic analysis of the virus showed that infection occurs more often from employee-to-employee than from patient-to-employee. In addition, our results show that there appears to be a certain cross-protection against SARS-CoV-2 thanks to previously acquired antibodies against another coronavirus that usually causes the common cold (OC43). Research into the immune response after vaccination shows that employees who have already been infected with SARS-CoV-2 showed a comparable or even better antibody response after 1 vaccination with BNT162b2 (Pfizer) compared to employees who have not previously been infected after 2 vaccinations. The results of this research are important in the areas of infection prevention, vaccine development and vaccination policy. Results: - Article about SARS-CoV-2 infections in different groups of hospital employees - Article about postponing the second mRNA vaccination in people previously infected with SARS-CoV-2 - Article about one-off mRA vaccination after previous infection with SARS-CoV-2 - Article about the effect of natural infection and vaccination against three variants of concern (VOCs)",,2022,Amsterdam UMC - locatie VUmc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation",Immunity | Disease surveillance & mapping | Characterisation of vaccine-induced immunity,2020 +P29610,1.035E+13,Vitalis makes sense of COVID-19 PHASE 1,"Alternative implementation of projects during corona. The new normal, the one and a half meter society, brings many changes. On the one hand we have residents who are lonely and isolated, on the other hand we have artists who are at home, but can offer a solution to break the loneliness and isolation, to provide meaning and interpretation in cultural or intellectual level. The new intelligent visiting options, the special corona meeting rooms, from Vitalis Woon Zorg Group create space for the artists to really work together with residents again, face to face.",,2020,Vitalis WoonZorg Groep,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29611,1.043E+13,Healthy daytime activities for people with an intellectual disability in corona times (and beyond),"The COVID-19 (corona) pandemic has major consequences for people with an intellectual disability (ID). This gives them fear of infection and stress because their regular daily rhythm has been disrupted due to restrictions in their daytime activities as a result of the corona measures. This can cause psychological and behavioral problems. In this project, a daytime offering for people with ID is developed with a fixed structure focused on health and well-being. It consists of educational, exercise, experience and cultural activities, individually or in groups, that can be used flexibly depending on the corona measures. The effect of daytime activities on quality of life and satisfaction with it is measured with questionnaires. The number of infections with the virus and the application of corona measures are monitored. The project is carried out by the Academic Workshop on Intellectual Disability and Mental Health in collaboration with local municipalities.",,2021,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Disabled persons,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29613,1.043E+13,CenteringOnline home test kit,"Centering Pregnancy is prenatal group care that combines medical checks with knowledge sharing, joint learning and the creation of a social network. This care provides better pregnancy outcomes and women are more satisfied. Contacts have currently been reduced to prevent the spread of COVID-19. Physical meetings have stopped and been replaced by online meetings. Medical checks still take place at the midwife's office. Goal To support pregnant women during the Corona pandemic and shorten contacts, they can carry out some of the checks themselves at home with a home test kit. TNO put together the kit with midwives and pregnant women and tested it. The home test kit consisted of a blood pressure monitor, glucose meter, urine strips and a card for recording child movements, lifestyle & well-being of the mother. Results Pregnant women and midwives are positive about the home test kit. They see it as a good addition (not a replacement) to existing care.",,2021,TNO,,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +P29614,1.043E+13,Real-time monitoring in home rehabilitation of patients with a COVID-19 infection after admission to the ICU of a hospital (REACH+),"Goal In the past year (until March 26, 2021), 51,000 patients were admitted to hospital as a result of a Covid-19 infection and thousands more patients who suffered symptoms but were not admitted to hospital. One of the most commonly reported complaints among patients is fatigue. Rehabilitation after a Covid-19 infection is unpredictable and little is known about recovery. Information about the patient's load and capacity can help to prevent under- and overload. Monitoring vital functions such as activity, heart rate and oxygen levels can provide support. Results This REACH+ pilot project has shown that real-time monitoring of patients in the home situation is feasible, but that both the patient and healthcare provider must be guided in the use of the App and measuring equipment. An App with clear instructions suitable for people with limited language and health skills is a prerequisite.",,2021,Hogeschool van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Health service delivery",2020 +P29615,1.043E+13,The effect of Covid-19 on the innovation and corporate venturing activities of organizations.,"Goal As a result of the Covid-19 pandemic, companies' innovation activities, especially those that are more exploratory in nature and where companies collaborate with external startups, have come under pressure. This research attempted to determine the effects of the pandemic on the innovation and corporate venturing activities of organizations. Which factors determine whether innovation and corporate venturing activities can survive a crisis such as Covid-19? Results Based on questionnaire research and interviews with more than 40 companies in the Netherlands, we have provided insight into which factors contribute to the resilience of innovation and corporate venturing activities. Based on these findings, we have developed a 'Pandemic Resilience Scan' with which companies can map their resilience themselves. In addition, we have mapped out the best practices to provide companies with tools for innovation management in times of crisis and to help them better protect their innovation activities in the future. The results can be found at www.corporateventuringentrepreneurship.com .",,2021,Erasmus University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29616,1.043E+13,An ethical framework for social work,"Goal The aim of this research project was to develop an ethical guide for social professionals in times of crisis. The reason for this was the Covid-19 pandemic in 2020 and its impact on the social domain. Results In the project, together with social professionals, an inventory was made of the various ethical challenges that occur in the social domain and what needs they had for ethical guidance during the Covid-19 pandemic. To this end, we have introduced an ideal-typical distinction into five forms of ethical guidance: substantive, reflective, communicative, procedural and process-based. This design led to greater insight into ethical needs at multiple levels: individual, organizational and societal. This has resulted in ethical guidance for social professionals in crisis situations. This guidance appears to be applicable much more broadly than just for social professionals and only for crisis situations. The guide can also be used for vertical consultation within organizations, for coordination across organizational boundaries and also in more everyday situations that cannot be characterized as a crisis.",,2021,Hogeschool Utrecht,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Research to inform ethical issues,,2020 +P29617,1.043E+13,Online Centering Corona for Eritrean pregnant women and mothers,"Cause Within the Eritrean community, midwives see that incorrect information about corona is being shared. This leads to fear and evasion of care, women no longer dare to give birth in the hospital or they avoid checks with their midwife. At CenteringPregnancy, individual contact moments with the midwife are replaced by group meetings to exchange ideas and share experiences in the field of pregnancy, childbirth and maternity care. Since COVID-19, physical group meetings have stopped and online group meetings have started; CenteringOnline. Goal The aim of this project is to offer CenteringOnline for Eritrean pregnant women, to give these women access to the correct information about corona and pregnancy, childbirth and postpartum. Results There is an information film and an information sheet developed for Eritrean pregnant women. In addition, a number of CenteringOnline meetings were organized with Eritrean pregnant women. The meetings ensured solidarity between the women and that the women were well informed. The Eritrean pregnant women and midwives were satisfied with CenteringOnline meetings, with the film and the fact sheet. We conducted an interview with Anne Bedaux in which we told more about Online Centering. Anne is an experienced midwife and has run the Online Centering groups.",,2021,TNO,,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29618,1.043E+13,Does the corona crisis lead to a worse working relationship between practitioners and vulnerable families?,"Cause The COVID-19 pandemic led to a lockdown, with mental health treatments switching to video calling (for example via Zoom or WhatsApp). This project investigated whether the working relationship between practitioners and parents was influenced by video calling. A strong working relationship is essential for good care. We looked at 846 families with multiple problems who received multisystem therapy (MST) before or during the lockdown. Results The working relationship was not affected by the use of video calling. Families with concerns about child abuse or neglect did report lower working relationships during the lockdown. Conclusions In intensive system therapy, a strong working relationship can also be built up via video calling. Video calling therefore seems to be a good enough alternative to face-to-face treatment. We don't yet know whether video calling will help solve the problems just as well. Video calling may be less suitable for families where there is a suspicion of child abuse or neglect. More research is needed into this.",,2021,Tilburg University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29619,1.043E+13,"Needs assessment for psychosocial and practical assistance for citizens, informal caregivers and surviving relatives affected by Corona in North Brabant.","Cause What aftercare needs were there after the first outbreak of COVID-19 in the spring of 2020? Could people also have somewhere to turn to with their concerns and problems after the illness? To answer these questions, fifteen conversations were held in the summer of 2020 with former patients who had been in home quarantine or in the ICU, and relatives of those who had died from the disease. All interviewees are from North Brabant, which was hit hard in the first wave. Approach Guidance and support in difficult times It turns out that people experience the disease differently. However, fear and uncertainty (about the disease itself, infecting others) are common. It was also sometimes difficult to receive support from the GP, for example after admission or death of a loved one. The supply is fragmented and many could not find the right aftercare. That is why peer groups have been started and the subject of aftercare is now on the agenda of the overarching PSH network steering group in Brabant. The aim is to form good local coalitions between the medical and social domains in order to improve psychosocial aftercare now and in the future. to organise.",,2021,Tilburg University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29620,1.043E+13,Online Vocational Therapy. Being tele-present as a professional therapist,"Cause Due to COVID-19, the professional therapeutic treatment was delayed. A survey among 281 professional therapists shows that 91% have 'completely/almost no' experience with working online. This action research used the Lean startup method. It was investigated how professional therapy can be used with 1) a virtual reality therapy room, 2) a 3D painting app and 3) an app for monitoring emotion regulation. Results Sixteen occupational therapists participated. Of the participants, 71.25% subsequently indicated that they had more knowledge and skills in offering online professional therapy. Pre-set goals such as 'more competence in online occupational therapy' and 'professional therapists gain more access to online tools that are better suited to occupational therapy' have been achieved. The professional therapists were trained and developed a methodology for using digital resources in professional therapy. An online training was also developed. The VR environment was further adapted to the wishes of professional therapists.",,2021,Hogeschool van Arnhem en Nijmegen,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29621,1.043E+13,"The ""three good questions"" to reduce emotional burden on nurses (in training) during the COVID-19 outbreak.","Cause Working in healthcare during the COVID-19 outbreak demands a lot from nurses (in training). During and after the COVID-19 outbreak, there must be attention and support for nurses (in training) in all healthcare sectors. Collard & Vermeulen (2020) formulated 3 questions for nurses who have to do their work in the current extreme circumstances. Results This research shows that nurses (in training) experienced emotional and physical overload during the COVID-19 outbreak. Nurses (in training) experience peer support within their own team or from their training as positive during their work in the COVID-19 outbreak. Applying the 3-question method offers added value in dealing with this overload. The 3-question method can be applied proactively (and informally) within education, during intervision meetings and study career guidance. The 3-question method can be applied proactively (and informally) by managers and colleagues in practice, during the coffee or lunch break and transfer moments (day evaluations).",,2021,Avans Hogeschool,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Nurses and Nursing Staff,Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2020 +P29622,1.043E+13,First-line COVID-19 portal: Development of best practices for first-line COVID-19 rehabilitation based on digital knowledge sharing.,"Cause Due to COVID-19, the pressure on healthcare increased exponentially. Healthcare providers in hospitals (secondary and tertiary care) and in care practices outside of them (primary care) were confronted with a new clinical picture that has a long-term impact on the functioning of patients. While the care processes for this new target group are concentrated and organized in hospitals, individual healthcare professionals in primary care practices are still searching. Protocols and knowledge about effective COVID-19 rehabilitation are still often lacking. That is why these healthcare professionals experience a great need for mutual information sharing and communication around the patient. A complete overview of diagnoses and treatment should provide insights into effective, efficient COVID-19 rehabilitation. Results The first-line COVID-19 portal offers a radically new approach to information sharing and communication around an individual patient, whose wishes and needs are the starting point for treatment. The healthcare professionals involved can at any time consult 'real time' information via the portal about activities related to the healthcare demand that are known from various sources.",,2021,Hogeschool van Arnhem en Nijmegen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P29623,1.043E+13,"Optimization of EMDR and Exposure within mental health care, new applications of trauma treatment when Face-to-Face treatments are not possible due to COVID-19","Goal This project was realized in close collaboration with UM and Mondriaan with the aim of ensuring the continuity of evidence-based care for trauma-related complaints through an innovative EMDR online application to investigate. Results Although innovation in healthcare is important, the process is often difficult. Obstacles that emerge include inadequate technical skills/capabilities, limited time and space as well as specific practitioner factors. In particular, practitioners who were positive about the innovation and their own skills actually tested the application. The application was experienced as user-friendly by both practitioners and clients. The greatest added value was seen in the accessibility, flexibility and better continuity of care. Clients were also quite satisfied with the online treatment and recovered sufficiently after the EMDR treatment. We therefore recommend including EMDR online treatments in the healthcare financing of trauma treatments.",,2021,Maastricht University,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29624,1.043E+13,"Supporting young people Young people participate fully in society, especially in times of Corona measures","Cause 8,400 young people live in the Utrecht district of Vleuten De Meern. Most are doing well, but some have problems such as dropping out of school, unsafe family situations, unemployment and/or debts. This prevents them from fully participating in society. Welfare work has difficulty reaching them. Activities Due to Covid-19, many leisure activities had been cancelled. MBO/HBO students and young people in the neighborhood have developed corona-proof activities such as dance/graffiti/skateboard workshops/digital quizzes/sports activities. This way young people could meet each other and us and connect and stay connected Approach The initiative lies with Durf! (www.durf.nl ), a project of Utrecht University of Applied Sciences, DOCK, Cultuur19 Stichting-JOU and the municipality of Utrecht. Students worked on activating young people based on the principle for young people by young people, in which Social Media played a central role. These activities have been developed and monitored through focus groups, questionnaires and observations. Yield In addition to scientific insights, this project provides concrete tools on how to approach young people, via social media but also directly. Educational learning materials have also been developed.",,2021,Hogeschool Utrecht,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29625,1.043E+13,EARLY DETECTION OF VESSEL DAMAGE IN PATIENTS AFTER COVID-19.,"Cause The coronavirus (SARS-CoV-2) causes the disease COVID-19, which can lead to damage to the inside of the blood vessels. If this damage continues for a long time, it leads to an increased risk of cardiovascular disease in the long term. We investigated this blood vessel damage in 203 COVID-19 patients diagnosed at the Bernhoven hospital during the first wave (February to May 2020). Results These patients underwent a test to map blood vessel damage 6 to 20 weeks after recovery from COVID-19. These test results have been compared with test results from a control group consisting of patients and healthy volunteers who have not had COVID-19. The presence of blood vessel damage in COVID-19 patients was comparable to that of the control group, 22.5% and 18.6%, respectively. These results are an important first indication that COVID-19 does not lead to permanent vascular damage.",,2021,Radboudumc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity | Disease pathogenesis | Post acute and long term health consequences,2020 +P29626,1.043E+13,Towards strengthening the resilience of the book world after Covid-19,"Goal In collaboration with representatives of Dutch authors, publishers, booksellers, libraries, reading promoters, knowledge institutes and government, this research maps the impact of the corona crisis. Central questions in the research are: which support measures and citizen initiatives have had what effect? What forms of cooperation could strengthen the sector? Results The Dutch book sector has proven to be vulnerable in the corona crisis: bookstores and authors in particular are having a hard time. Physical bookstores face a lot of competition from online bookstores, authors earn less from the sale of books and miss out on income from performances. That vulnerability will probably not decrease in 2021. However, there are opportunities for recovery: the sector is well organized and the sector players agree on core values. Making literature accessible - for example through reading promotion projects for children and young people - is generally seen as the most important value; Collaboration within the sector is also considered crucial. Based on these core values, the sector can make itself more resilient: this requires further protection of vulnerable players and the implementation of strict policies on reading promotion and inequality of opportunity in reading education and to work more closely together, for example in the online sale of books.",,2021,Universiteit Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29627,1.043E+13,"Increasing qualitative insight into the target group of Utrecht self-employed people and small entrepreneurs affected by COVID-19 to help them avoid debts, work on their resilience and increase a sustainable future perspective.","Cause In recent months, more than 10,000 self-employed people and small entrepreneurs have turned to the municipality of Utrecht for financial help due to the consequences of COVID-19 in the form of a Tozo scheme. Quantitatively speaking, this group of small entrepreneurs is well visible, but numerical data only provide limited insight into this target group. Municipalities are also looking for qualitative information that can help develop policy to support this target group. With this research we want to gain insight into the financial-economic, psychological and social impact of COVID-19 on Utrecht self-employed people and small entrepreneurs so that the municipality of Utrecht can develop policy that offers this target group a sustainable perspective. Results Small entrepreneurs and self-employed people from the Utrecht region have been hit hard by COVID-19; 51% of respondents can only last a maximum of 2 months with their financial reserves. In addition, 41% have debts or payment arrears and a quarter to 59% are barely able to provide for their daily subsistence. On the positive side, these small entrepreneurs and self-employed people appear to have perseverance, creativity and optimism in dealing with the worries and stress that the crisis causes them. In terms of further support, there was a particular need for financial help (64%), retraining (29%) and contact with other entrepreneurs (29%). Based on these results, the municipality of Utrecht has drawn up a three-pronged policy aimed at: 1) Quick help with (initial) debts or payment arrears; 2) Assistance/support in continuing the business; and 3) Guidance towards paid work. These are positively received by small entrepreneurs from the region and additional support needs have been mentioned.",,2020,Hogeschool Utrecht,,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2020 +P29628,1.043E+13,The added value of IS-pro technology in the emergency room in identifying a bacterial infection and predicting the severity of SARS-CoV-2 in patients with suspected COVID-19?,Resume,,2021,Amsterdam UMC - locatie VUmc,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,,2020 +P29629,1.043E+13,Adaptation and Effects of Social-VR as a Tool for Overcoming Social Distance in Higher Education,"The measures taken to combat the Covid-19 pandemic are having a negative impact on the social lives of university students, which can have detrimental effects on their psychological well-being and motivation. This project proposes to provide a group of students with consumer-grade VR devices and access to a new ""VR campus"" application. Students will be involved in a range of collaborative tasks and social activities on this VR campus over two months, and their impact on students' well-being and motivation will be explored. The results will reveal the practical aspects that need to be taken into account for a wider application of consumer-grade Virtual Reality technology to improve the difficult social, (mental) health and educational situation of students due to the Corona crisis.",,2021,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29630,1.04301E+13,BACILLUS CALMETTE-GUÉRIN VACCINATION TO PREVENT SERIOUS RESPIRATORY TRACT INFECTION AND COVID-19 IN VULNERABLE ELDERLY - AN ADAPTIVE RANDOMIZED CONTROLLED TRIAL (BCG-PRIME),"Elderly people with a chronic illness have an increased risk of serious COVID-19 infection. In the BCG-PRIME study we investigated whether the tuberculosis vaccine (BCG vaccine) reduces the risk or severity of COVID-19. The research shows that this is not the case. Therefore, the BCG vaccine has no place in protection against COVID-19. People aged 60 or older with chronic diseases received raffle BCG or a placebo vaccination administered. They then kept data for 6 months on respiratory complaints, COVID-19 tests and contacts with their GP. Participants who received BCG were just as likely to have COVID-19 and were hospitalized for COVID-19 as participants who received placebo. The number of respiratory infections treated by a doctor also did not differ. The study was conducted in 20 hospitals in the Netherlands, including 7 academic hospitals and 15 non-academic hospitals. The research was coordinated by the UMC Utrecht. Also read: Tuberculosis vaccine does not prevent corona infection (NRC, January 18) Does the BCG Vaccine Protect Our Vulnerable Elderly? (film, UMC Utrecht, Oct 2020) Research the effect of BCG vaccine against the consequences of COVID-19 in vulnerable elderly people (Sep 2020) More information Research into corona and COVID-19",,2023,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Randomized Controlled Trial,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Characterisation of vaccine-induced immunity,2020 +P29631,1.043E+13,eCOFIT+: ehealth to support geriatric outpatient rehabilitation,"Cause GRZPLUS (Omring + Zorgkring) offers the CO FIT+ program for geriatric rehabilitation after a COVID-19 infection. In order to monitor and guide functioning in the home situation, activity monitoring has been used in combination with coaching (Hopper system) and remote guidance (including video calling). Goal Making activity monitoring combined with remote guidance applicable in the CO FIT+ rehabilitation program for geriatric rehabilitation patients who have experienced COVID-19. Results This project shows that activity monitoring has added value for the treatment of geriatric rehabilitation patients in recovery after COVID-19. Activity monitoring must be used for a clear purpose with the rehabilitation patient and this must be clearly discussed with the rehabilitation patient. Although video calling has not yet been included in the rehabilitation program, both rehabilitators and healthcare professionals are open to its application.",,2021,Hogeschool van Amsterdam,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29632,1.043E+13,"SARSLIVA and utility of saliva in diagnosis for wide scale testing, including viral and SARS-CoV-2 antibody detection in pre- and asymptomatic persons and follow-up of infections in COVID-19 patient; a house hold study","High level of spread of the coronavirus within households - results of the SARSLIVA study A total of 85 households (326 adults and children) participated in the SARSLIVA study. The study lasted 6 weeks and participants collected saliva themselves at 10 times with a tube or, for the little ones, with a so-called 'sucking cotton ball'. The research team also collected a nasal swab, throat swab and a finger prick from the participants. The most important outcome of the SARSLIVA study is that a high degree of spread of the coronavirus within households was found due to the frequent collection of saliva in combination with swabs and blood collection to determine antibodies. In 88% of households where someone was infected with the coronavirus, one or more housemates also became infected. These results also show that taking saliva can be an attractive way to investigate the spread of the coronavirus.",,2022,Spaarne Gasthuis,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Diagnostics | Disease transmission dynamics,2020 +P29633,1.043E+13,Impact of the COVID-19 pandemic on patients with an inflammatory rheumatic disease,"The study was originally designed to investigate whether patients with a rheumatic disease become more seriously ill from a SARS-CoV-2 infection compared to healthy control participants, and what the effect of immunosuppressive medications is on this. To answer these questions, we set up a digital research platform and used finger pricks to collect blood from participants. This combination allowed data collection to take place completely remotely, which greatly increased efficiency. The most important outcome of the study is that most patients with rheumatic diseases do not have an increased risk of hospitalization due to a corona infection, with the exception of patients treated with B-cell inhibitors. In addition, we saw that antibody production after corona vaccinations was greatly reduced in patients who received B-cell inhibitors. Thus, our results emphasize that it is important for rheumatologists to be cautious when prescribing B-cell inhibitors.",,2022,Reade,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Prognostic factors for disease severity,2020 +P29634,1.043E+13,Influence of large (running) events on the COVID-19 infection rate.,"Goal The COVID-19 pandemic affects our sports behavior. Through a questionnaire survey among more than 4,000 people, we mapped out the impact of a COVID-19 infection on sports patterns. Results The results of this study show that people exercise less during the COVID-19 pandemic, with a greater decrease in exercise behavior seen in people who have experienced a COVID-19 infection. In these individuals, physical activity 1 month and 3 months after the COVID-19 infection was 42% and 25% lower, respectively, than before the COVID-19 pandemic. Factors that influence this decrease in sports behavior are having a medical history of a disease and being older than 50 years. In addition, we also looked at the main reasons for changes in sports behavior. This shows that COVID-19 related symptoms such as fatigue, shortness of breath and general malaise are the main reason why people exercise less after 1 and 3 months after a COVID-19 infection.",,2021,Radboudumc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures",Post acute and long term health consequences | Indirect health impacts,2020 +P29635,1.043E+13,MONDIAL: Mouth and nose masks: alternatives to the surgical mouth and nose mask,"Background There is a global shortage of medical-grade face masks. At the same time, face masks can play an important role in limiting the spread of SARS-CoV-2. This project investigates whether there is an effective mask for the public to wear in public that can be made from readily available materials. Results The best alternative to a medical face mask is a mask made from a ventilation system filter. This mouth and nose mask is more effective than masks labelled as ""surgical masks"", if properly made. With filter class ePM1 85%, which indicates how many fine dust particles it filters, you approach the capacity of an FFP2 mask used in healthcare. In the tests, a mask with the shape of a duckbill worked best because it seals better. A mask made of two layers of cotton fabric with kitchen paper in between as a filter is a reasonable alternative made from more available materials. The filter test was done in a so-called particle chamber where particles as large as a virus particle are sucked in. The number of particles sucked through the fabric was measured. In addition, it was examined which materials and models fit the skin best, whether the materials breathe sufficiently and whether they could be washed.",,2020,Erasmus MC,,Other,Not applicable,Unspecified,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P29636,838002516,Monitor patients' vital values ​​remotely,"At the beginning of April, Santiz, Sensire, Ascom and Mediq mapped out how Smart Monitoring Covid 19 can be realized for clients in the Achterhoek care hotel. The Achterhoek care hotel provides care to clients who no longer need intensive monitoring within the hospital, but where care in the home situation is still too complex, unpredictable or intensive. The exploration assumed that this could offer added value. The available functions are: Measurement and monitoring of heart rate and respiratory rate (continuous measurements and monitoring) Saturation measurement (point measurements and monitoring) At the beginning of May, the monitoring was tested for a few days for 2 clients in the care hotel. These were clients who had already recovered quite well and wanted to cooperate. Despite the limited scale, insights have been gained with this test. We take this into account when considering how we can optimally facilitate care in the event of a possible new Covid-19 period.",,2021,NAAST,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P29637,1.043E+13,"New rules, new possibilities: Construction work in times of Corona","Objective This project investigated the challenges for community development in times of COVID-19 and the 1.5-meter society. It was analyzed how community development can also take shape in times of a pandemic. Results Results show that COVID-19 puts pressure on the three basic tasks of community development - protecting & strengthening, stimulating & supporting, connecting & influencing. The core tasks of community development hardly take shape without the physical presence of the community worker in the neighborhood. Results show that the many informal connections between citizens are being eroded: not only because of the practical obstacles resulting from physical distance, but also because of a changing motivation and attitude of citizens. To deal with challenges, community workers apply various strategies such as silent, explicit and creative resistance; the principle of Kan-Wel; forging alliances and offering practical support. Continuing to adapt, thinking in scenarios and looking at what is possible remains the credo for community workers in times of COVID-19 and the future.",,2021,Zuyd Hogeschool,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P29638,1.043E+13,"Talking with, instead of about, the elderly: Perceptions and practical needs of the elderly with regard to (relaxed) Covid-19 measures","Results What do the elderly think about the corona measures and what do they need? This research shows that elderly people largely agree with the corona measures, feel protected by them and follow them lawfully. At this time, the elderly miss social meeting places, organized activities and physical contact with loved ones. Single and 'older' elderly people (75+) in particular experience more loneliness. This shows the diversity of the age group of people aged 65 and over. This also underlines the importance of making a distinction between 'young' and 'older' elderly people and elderly people living alone and living together. Instead of emphasizing 'vulnerability', older people think it is important that more attention is paid to the resilience of the elderly in government and media messages. In addition, there is a need for a concrete and tailor-made translation of measures into common, everyday situations. These results and advice inform local and national government agencies and older people's organizations about the perceptions and practical needs of older people. This can make an important contribution to the development of policy and adjustment of corona measures.",,2021,Radboudumc,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Approaches to public health interventions | Social impacts,2020 +P29639,1.043E+13,Communication between healthcare workers and deaf patients in times of COVID-19,"Cause Communication between healthcare workers and deaf patients is extra difficult in times of COVID-19. Interpreters are often not allowed to come along and the healthcare staff wear face masks, which means that lip reading is not possible. This makes proper diagnosis, treatment, explanation and obtaining informed consent virtually impossible. Within the project, research was conducted into the experiences and communication needs of deaf people patients during the pandemic. Results This shows that many people are afraid of Corona and access to care during the Corona pandemic. Due to the use of face masks, they cannot understand the healthcare workers, the use of interpreters is more limited and their experience is that healthcare workers do not know how to communicate with them. The research shows a great appreciation for accessible information provision, such as subtitling or translation into NGT, but the quality of these facilities varies and needs to be better guaranteed. In addition, software has been developed that translates frequently asked questions and communications in COVID-19 related care into Dutch Sign Language (NGT). Translations in NGT are shown using videos in which a deaf person gestures and uses the translations an avatar. The video translations are of better quality, but the avatar offers more flexibility and will be particularly useful for other applications in the future",,2020,Universiteit van Amsterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Other,Health Personnel,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29640,1.043E+13,The COFIT-20 project: encouraging physical activity through online livestream group classes for people with serious mental illness during COVID-19,"Goal The COFIT-20 study will examine 40 people with a psychiatric condition: 20 people participate in the sports group and 20 in the control group. The sports group participates in fitness or pilates twice a week via video connection for 12 weeks. In small groups, they receive live feedback from a sports coach and discuss before and after the lesson how they experienced the sport. Results The COFIT-20 program focuses on sports via a live video calling connection for people with a psychiatric vulnerability. The research shows that people with a psychiatric vulnerability find it pleasant and accessible to exercise in this way. 55% even said they felt less lonely. In addition, we saw that the physical and mental quality of life of the participants improved. These findings are very important. The corona pandemic has a negative effect on people's mental and physical health, and this affects people with psychiatric vulnerability even more. The COFIT-20 program could potentially reduce these negative consequences.",,2021,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29641,1.043E+13,Population differences in diagnosed Covid-19 prevalence in the Netherlands: Which groups are at highest risk?,"Every resident has the right to protection against the COVID-19 virus. In this study, differences in GGD test street visits and infection rates between groups of residents were studied. COVID registration data from three GGDs were linked to data from Statistics Netherlands on socio-economic position, demography, living and working conditions. Mainly residents from private households with children had themselves tested at the GGD. The elderly, residents of (care) institutions and care workers were also regularly tested positive at other test locations. Due to differences in registration policies between test locations, not all groups of residents could be fairly compared. Differences between population groups in the development of the infection rate were numerically inconsistent over time. Conversations with residents confirm that their behavior has also fluctuated over time. Compliance with the behavioral measures was determined, among other things, by the perceived risk of becoming infected yourself, of infecting a vulnerable other person and the possibilities to remove yourself from risky situations.",,2022,Dienst Gezondheid & Jeugd ZHZ,,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years) | Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience",Disease susceptibility | Disease surveillance & mapping | Approaches to public health interventions,2020 +P29642,1.043E+13,"The social dynamics of the COVID-19 pandemic: education, socio-economic position and solidarity","The major social effects of the COVID-19 pandemic will not be equally distributed across society and existing inequalities in society may be reinforced as a result. A research team from the UvA, EUR and VU will therefore map the consequences of the coronavirus on social inequalities. Specifically, the research team looks at the areas of work and income, education, social-psychological well-being, and mutual solidarity and trust. They will look for social dividing lines, identify vulnerable groups, and formulate policy strategies for strengthening the resilience of individuals, organizations and society. The findings are relevant to society and science. This project is in line with another ZonMw-funded project: Social Impact of Physical Distancing on Vulnerable Populations during COVID-19 in the Netherlands. Goal Mapping the consequences of the COVID-19 pandemic on social inequalities. Research design Use new data to map the consequences of the pandemic and existing data to identify vulnerable groups. First results Education Inequalities in education are reinforced Home schooling Loss of final test and adjustment of advice, lack of clarity of procedure Digital divide Policy implications Give students time and, if in doubt, give high advice Establish links between schools on both sides of the transition (primary/secondary) Commit to long-term recovery of backlogs Executive parties University of Amsterdam, Erasmus University Rotterdam and the Vrije Universiteit Amsterdam More information",,2021,Universiteit van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29643,1.043E+13,Healthcare logistics in the 1.5 meter society: A planning tool for Dutch hospitals,"Due to Covid-19 and the applicable 1.5 meter rule, hospitals can admit fewer patients into their waiting areas and therefore schedule fewer appointments. With a tool developed by the University of Groningen, departments at the Martini Hospital have managed to operate at full capacity again. Goal This study focused on how to limit the number of patients waiting in the waiting room. Research design Four measures have been examined and are part of the tool: Redesigning waiting rooms Reducing the number of appointments Introducing new organizational measures Designing new appointment schedules Results Using the tool, departments at the Martini Hospital have managed to return to full capacity as before corona. ""The tool provides appointment schedules, but also provides insight into the effect of practical and organizational measures,"" says Justin Drupsteen, manager of integrated capacity management at the Martini Hospital. ""The combination of a tool, measures and the flexible attitude of doctors means that we are back to pre-corona levels."" When making appointment schedules, hospitals try to help as many patients as possible, but now with Covid-19 the waiting room is leading and this requires a different way of planning. ""It's great to see that we were able to use inspiration from logistics to develop the tool,"" says Professor Iris Vis. The tool is available for hospitals and can be viewed on the RUG website .",,2021,Rijksuniversiteit Groningen,,Human Populations,Unspecified,Unspecified,Urban Population/Setting,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Infection prevention and control | Health Systems Research,IPC in health care settings | Health service delivery,2020 +P29644,1.043E+13,What does COVID-19 mean for the employability and resilience of vulnerable employees in facility services?,"Cause In the coming decade, many jobs in facility services are expected to disappear due to automation and robotization. The recent COVID-19 crisis and the rise of the one-and-a-half-meter society have accelerated this development. Many of these employees fall into vulnerable groups (female, 55+, migration background, poorly educated). They are faced with a great distance from the labor market, which can have a negative effect on their subjective well-being. Results Through literature research and econometric analyses, (1) insight has been provided into which strategies can be used by organizations in the facility services sector to, in the short term, prepare employees for changes in the sector and support them to increase their economic and mental resilience and (2) provided insight into which jobs in facility services are most vulnerable to disappearing in the short term and where there are (career) opportunities for employees who are in danger of losing their jobs.",,2021,Erasmus MC,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women | Vulnerable populations unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2020 +P29645,1.043E+13,"Relationship and family problems, care avoidance and prevention during and after COVID-19","Objective What is the impact of the Corona crisis on relationships and families? This study shows a picture of resilient relationships and families during the first and second wave. Results The majority reports no or positive changes in relationships and families due to the Corona crisis. At the same time, a small group does report problems, with possibly large ""hidden"" impact, and risk groups were less represented. Stress due to work, health, or finances is a risk factor for relationship and family problems, especially when people have little social support and partners do not deal well with stress together. The estimated effectiveness of (particularly online) care for relationship and family problems is limited, and lower than proven in effectiveness studies. A public campaign and better information provision could help with this. The accessibility of care during the Corona crisis is estimated by 20-30% as (very) difficult. This reinforces the concern that people do not find access to relationship and family therapy. Shorter waiting times and better cost reimbursement or compensation can make professional help more accessible.",,2021,Universiteit Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29646,1.043E+13,General practitioners and help-seeking behavior in deprived neighborhoods in the Covid-19 crisis,"Most patients of general practitioners in deprived areas said they found the Covid-19 rules important and did not find it difficult to comply with the rules. At the beginning of the Covid-19 epidemic, many patients thought that general practitioner care was unavailable. According to general practitioners, almost 90% of patient contacts were remote: by telephone, video calling or e-mail. Some general practitioners thought negatively about remote care for residents with less language skills or with low education. Results The research confirms that care for patients with a migration background was less often provided remotely during Covid-19 and that they visited GP consultations more often. It also emerged that people with chronic illnesses or financial problems more often had mental problems. Accessible facilities are recommended for these groups during the corona crisis. Good information is also needed about how infection can be prevented and how the GP can be reached.",,2021,Erasmus Universiteit Rotterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Social impacts,2020 +P29647,1.043E+13,"Providing tools to students in higher education in dealing with the new COVID-19 situation, through specially developed eHealth modules, in order to prevent stress and mental health complaints.","Cause Students in higher education, like many others, have been affected by the COVID-19 measures. Apart from a stripped-down form of education, students may face problems due to social and financial consequences. Goal To help students in higher education deal with the current situation as best as possible, the Student Doctors of the UvA make free eHealth modules available. The aim of following these eHealth modules is, among other things, to help students cope better with stress and better organize their studies in the current situation. Results With the help of virtual guidance, students were encouraged to get started and continue. This group was generally very positive about the modules. Expectations about techniques to deal with stress in a more structured way and to study at home have largely been met. The conclusion is that recruiting for participation remains the challenge.",,2021,Universiteit van Amsterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29649,838002507,Video calling in general practice,"The aim of this project is to use video calling in general practice to better reach patients. Due to the Covid-19 pandemic, it is currently not desirable to have many patients come to the GP practice for a physical appointment. By using screen care, patients can still have contact with their GP, practice nurse or doctor's assistant. During the Covid-19 pandemic, but also afterwards, screen care can improve the accessibility of the practice and the efficiency of communication between doctor and patient. With the help of an implementation coach, the right technology will be selected and an action plan will be drawn up and implemented. The coach will provide guidance in training healthcare providers on how to use the technology. In addition, patients and caregivers will be asked to provide feedback on the use of video calling.",,2020,Universiteit van Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29650,1.043E+13,CounterCOVID,"One in five patients with COVID-19 develops serious lung damage, requiring admission to a hospital or even to an Intensive Care Unit. This lung damage is caused, among other things, by leakage in the smallest blood vessels of the lung, whereby fluid escapes from the bloodstream and fills the alveoli. The fluid in the alveoli seriously impairs oxygen absorption, causing life-threatening oxygen deficiency. There are currently no medications to prevent leakage from small blood vessels. Research and expected outcomes Previous research in the laboratory has shown that the existing drug imatinib prevents blood vessel leakage. This protective effect of imatinib on the blood vessel wall can therefore possibly be used in patients with COVID-19. The COUNTER-COVID study tests whether patients treated with imatinib recover faster than patients who receive standard care.",,2023,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2020 +P29651,1.043E+13,Development and clinical evaluation of a rehabilitation protocol after COVID-19 with integration of technology and software.,"Purpose of the project Patients after COVID-19 infection sometimes face serious physical limitations. This requires rapid and intensive rehabilitation. At the moment, rehabilitation is not yet sufficient to support this recovery. This project focused on developing an effective and useful rehabilitation program for these patients. What did the program entail? The program consisted of exercises on a treadmill, training endurance and balance while walking. The use of game elements and so-called 'virtual reality' ensured that attention and concentration were also practiced. Muscle strength was trained on fitness equipment. All equipment and exercises were linked to an electronic patient file with the help of special software. This allowed the patient and therapist to closely monitor the progress of the therapy. The most important results Patients and therapists found it a valuable and useful program. After the program, patients suffered fewer limitations and were fitter. They also suffered less from fatigue and shortness of breath during and after exercise. Particular attention to so-called 'cognitive' tasks, such as concentration during exercise, proved to be very valuable.",,2021,Vrije Universiteit Amsterdam,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,Clinical characterisation and management,"Supportive care, processes of care and management | Post acute and long term health consequences",2020 +P29652,1.043E+13,Applicability of the POST-IC diary; a digital means of communication regarding admission to intensive care,"Cause The restriction of visits to intensive care (IC) departments during the outbreak of Covid-19 resulted in a huge lack of normal interpersonal contact. The implementation of the Post-IC diary, a digital personal logbook, enables closeness and interpersonal contact in the short term and reduces complaints of Post Intensive Care Syndrome (PICS) and PICS Family (PICS-F) in the long term. Results The Post-IC diary is an application in daily practice that meets person-oriented care; policy in which, among other things, individual needs and attention to optimal communication are essential. The results of the project show that ICU nurses endorse the added value of the intervention. However, they also experience challenges in writing short messages in the Post-IC diary themselves. For structural embedding, tailor-made strategies are required to support ICU nurses in the use of the Post-ICU diary.",,2021,Erasmus MC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2020 +P29654,1.043E+13,COVID-19: an accelerator of the collaboration of the acute care network in The Hague,"Cause The COVID-19 crisis has accelerated the collaboration between those involved in the acute care network, including the emergency department, GP post and the Regional Ambulance Facility, in the Haaglanden region. Goal Using COVID-19 as an accelerator of the collaboration of the acute care network in Haaglanden. To make the acute care network function more efficiently and maintain accessibility in the future, collaboration between healthcare providers, trade organizations and health insurers is the key. Results In order to continue to provide high-quality acute care, it is very important that all organizations involved are well integrated at all organizational levels. Consider, among other things, the emergency department (ED), general practitioner (HAP), ambulance service, but also nursing homes for the outflow of patients. The COVID-19 crisis acted as an accelerator for the collaboration within acute care networks. The aim of this study was to determine to what extent collaboration in a large city in the Netherlands (The Hague) improved as a result of the COVID-19 crisis. You can find the full article here read.",,2021,Leiden Universitair Medisch Centrum (LUMC),,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health leadership and governance,2020 +P29655,1.043E+13,"Disease, Social Memory and Resilience: A Competition for Artistic Research Expertise","Cause The COVID-19 crisis has had an enormous impact on our society for a year. But how will we look back on this difficult period? How do we reflect on the many victims who suffered from it? virus has claimed? Last summer, Utrecht University, in collaboration with the Centraal Museum and ZonMw, issued an open call for artistic research into a possible way on which the COVID-19 crisis can be commemorated. Two questions were central: How is illness experienced, documented and remembered by society and what is the role of art, artists and memory culture in such moments of crisis? The closing date of the open call was September 30, 2020. From the 23 entries, Rosa Everts, Sanne Kabalt and Bart Lunenburg selected as winners. The three winners each received 5,000 euros for their winning proposal. Artistic research into memory Rosa Everts' work Pandemic 2020 is a visual documentation of the pandemic. Everts shows detailed drawings of people who, despite their different appearances, all have one thing in common: wearing a face mask. Her work addresses human fragility and a possible universal experience of the pandemic. With the proposal for the art installation De Hoest, Sanne Kabalt visualizes the stories of corona patients. By showing the cough, Kabalt connects the personal experiences and impact of the virus with the public health debate. The cough is the focus here, because this is a symptom that is inevitably and sometimes wrongly linked to the virus. Her proposal focuses on the consequences and impact of the coronavirus on former corona patients. In his proposal, Bart Lunenburg examines the confinement and uncertainty of buildings. His proposal builds on an earlier work of his: Room with Windows. Lunenburg connects the history and memory of diseases to architecture. His work provides a new perspective on the universal sense of confinement we are currently experiencing during the pandemic. The healthy city Utrecht University (Department of Modern and Contemporary Art History/Department of Economic and Social History) initiated this competition. For the Centraal Museum, the competition is part of the preparation for the exhibition The Healthy City, which will open in June 2022. Utrecht University and the Centraal Museum are strengthening their collaboration in the field of (art) historical expertise and public outreach. The winners have been selected by Prof. Dr. Eva-Maria Troelenberg, Prof. Dr. Maarten Prak and Drs. René de Kam in consultation with the jury members Prof. Dr. Ann Rigney, Dr. Surekha Davies and Laurie Cluitmans MA.",,2021,Universiteit Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Secondary impacts of disease, response & control measures",,2020 +P29656,1.043E+13,LAMP-based molecular diagnostics of SARS-CoV-2,"Being able to quickly and efficiently determine whether someone is infected with the SARS CoV-2 Coronavirus is of great importance to prevent further spread of the infection. In the current approach, there are sensitive methods (including qPCR) available that are relatively slow (18-30 hours), and fast methods that are relatively insensitive. With an insensitive test, people can test negative who are still infected; A slow test result can lead to people being in quarantine for an unnecessarily long time, but it also increases the risk of infection when people do not strictly adhere to the quarantine measures. This project worked on an alternative RT-LAMP test method that is both fast and sensitive. The test method can be used at larger test locations by means of a 'pop-up lab'. Although the RT-LAMP test can generate a test result within 45 minutes, under practical conditions it has been shown that the test result can be delivered within two hours. To ensure that the new test method is less sensitive to shortages in reagents and laboratory supplies, a production method has been set up for critical reagents.",,2021,TNO,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P29657,1.043E+13,The COVID-19 Public Transport Capacity Model: a policy supporting instrument for optimizing the corona capacity of public transport,"Goal The COVID-19 pandemic has major consequences for public transport. In this project, a new public transport model for public transport in Twente has been developed. The model optimizes bus transport based on, among other things, the number of travelers and the costs of using buses. The effects of the pandemic have been examined for different traveler groups, time periods (peak, off-peak), routes and locations. Results Applications of the model show that it is possible for the examined bus lines in Twente to meet the more limited transport demand during the pandemic (April 2020 level) when all seats on the buses are available. Furthermore, public transport in Twente can be organized more efficiently during the pandemic by limiting the transport supply outside rush hours and shifting transport demand during the morning rush hour by changing the start times of physical educational activities in higher education.",,2020,Universiteit Twente,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Impact/ effectiveness of control measures | Social impacts,2020 +P29658,1.043E+13,Educational partnership in remote VVE: effective principles in providing virtual support to parents of at-risk students,"Parents are important partners in early childhood education (ECE) programs aimed at preventing educational disadvantages. As a result of the COVID-19 measures, support for parents who participate in such programs has come under pressure. The Dutch Expertise Center (Nijmegen) and the PAS Foundation (Arnhem) have therefore investigated in this project how parents were involved before/during and after the lockdown, what bottlenecks were experienced, but what also worked when offering remote support from the VVE. . Goal This project investigated how parents were involved in VVE programs, before/during/after the lockdown, what bottlenecks were experienced, but also what effective practices have proven to be effective in providing remote support to parents in the context of VVE. Two questions were central: How have the VVE services progressed during the COVID-19 measures from the perspective of professionals and parents? What are effective practices when providing remote HOA? Research design A national exploration was carried out using a digital questionnaire, interviews with a number of VVE professionals and a structured review of scientific sources. Results Based on the survey results, the following effective practices for providing remote support to parents have been suggested: Reciprocity in contact with parents; Clear communication; Combination of media (spoken, written and image); Different communication channels (both synchronous and asynchronous); Taking diversity into account; Request feedback; Digital skills; Provide an overview; Modeling; Expand parent networks. You can read more information about the results in the report and the flyer for VVE providers",,2020,Expertisecentrum Nederlands,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P29659,1.043E+13,The course of Acute Myocardial Infarction during the COVID-19 lock down in high and low endemic COVID-19 regions in the Netherlands,"Background At the time of the first COVID-19 outbreak in the Netherlands, there was a fear that this could jeopardize acute heart attack care in the Netherlands. In the case of an acute heart attack, it is important to keep the time loss between the onset of symptoms and treatment (opening the artery to the heart by angioplasty) as short as possible. Time loss can be caused by various factors. For example: the patient does not dare to sound the alarm for fear of infection in the hospital, the ambulance is too busy transporting COVID patients. In this study, we have mapped out the time factors. Objective The aim of this study is to investigate whether patients with an acute heart attack in the COVID-19 period waited longer to seek medical help or whether medical help took longer to arrive and what the consequences are. Study design This is a retrospective cohort study into the effect of the COVID-19 outbreak on both patient and system delay and the prevention of cardiovascular complications and mortality of acute heart attacks in the Netherlands. These results were compared with the results of 2019 and regional differences between the Northern Netherlands (low endemic area) and North Brabant (high endemic area) were mapped. First results This study shows that treatment delay in patients with ST-elevation myocardial infarction (STEMI) increased during the COVID-19 outbreak. This became visible when patients during the COVID-19 outbreak were compared with patients from 2019 (before the outbreak). The same difference was also found when patients from a high endemic COVID-19 area (North Brabant) were compared with patients from a low endemic COVID-19 area (North Netherlands). The increase was caused by a longer patient delay (when patients wait longer to seek medical help). The system delay remained stable. This means that the STEMI care network continued to function well during the COVID-19 outbreak. The study also shows that mortality and complications in STEMI patients did not increase during the COVID-19 outbreak. Since STEMI patients benefit from a short treatment delay, patients should be encouraged to continue reporting acute cardiac complaints. Even in times of crisis.",,2020,Technische Universiteit Eindhoven,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29660,1.043E+13,Dynamics between national document drug treatment options and prescribing behavior in hospitals during the COVID-19 pandemic,"Cause At the beginning of the corona pandemic, much was unknown about which (regular) medicines would have a clinical effect in COVID-19 patients. To support hospitals in making local policy, the Antibiotic Policy Working Group Foundation (SWAB) has developed a document with medicinal treatment options that is frequently updated with the latest scientific insights. Results This study with data from more than 1,500 patients from six Dutch hospitals has shown that at the start of the COVID-19 pandemic, all hospitals immediately started prescribing (hydroxy)chloroquine to almost all patients. Other medicines that might be effective against COVID-19 were hardly prescribed. The more unanimously the hospitals started using (hydroxy)chloroquine, the more differently they stopped using it. The moment when (hydroxy)chloroquine was no longer prescribed differed by up to 4 weeks between hospitals. None of the hospitals still used (hydroxy)chloroquine after SWAB recommended no longer using (hydroxy)chloroquine. All hospitals have indicated that the local treatment policy was designed based on their own assessment of the scientific literature in combination with information from the SWAB national advice document.",,2020,Universiteit Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Health Systems Research,Health leadership and governance,2020 +P29661,1.043E+13,"Neighborhood-oriented follow-up of opening up sports fields and schools in Leiden, the COVID Radar in practice","The ""Covid Radar"" app was launched in April 2020 from the Leiden University Medical Center to collect large-scale data about health, symptoms and behavior related to COVID-19. Because this data has been collected repeatedly since the start of the outbreak, it can provide insight into whether there are early indications of a next Corona wave and provide support for regional health policy. Results Based on more than 285,000 unique users, it was seen that the trends in behavior and symptoms reported from the app are in line with the national trends reported by the RIVM. In addition, a clear and strong connection was found between symptoms and behavior and the number of cases with Covid-19 in the region, where this connection was already observed a week prior to a positive test result. Based on this, the Covid radar data is now updated weekly regional GGDs shared to further support health policy.",,2021,Leiden Universitair Medisch Centrum (LUMC),,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2020 +P29662,1.043E+13,"Conditions for technological solutions in a Covid-19 exit strategy, with particular focus on the legal and societal conditions","Digital solutions can contribute to controlling the current Covid-19 pandemic. The current discussion about contact tracing apps in particular also brings new challenges, such as how we can implement these technologies in a way that takes into account both the fundamental rights of the individual and the need for democratic control. This research therefore focuses on the question of which legal, ethical and social conditions must be met for the use of digital solutions in the Covid-19 exit strategy. In addition to an in-depth analysis of legal and social conditions regarding the implementation of digital solutions, empirical research is also used into the perceptions and experiences of users, and the impact on society. The research is led by Prof. Natali Helberger, Prof. Claes de Vreese, Prof. Joris van Hoboken and Prof. Mireille van Eechoud. They are assisted by a group of experts and the interdisciplinary research team of Digital Transformation and Information and Communication & the Data Society, two research initiatives at the UvA.",,2021,Universiteit van Amsterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Digital Health,,,Netherlands,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues related to Public Health Measures | Approaches to public health interventions,2020 +P29663,1.043E+13,Working together against Corona with Intensive Care Data,"Treatment in intensive care appears to be necessary for many COVID-19 patients. It is very important to gain more insight into the disease course of intensive care patients with COVID-19 and the factors that influence this. This can provide direction for the treatment of future patients, help with the choice of who should and should not be treated in intensive care and contribute to future capacity planning. Research The project investigates which combination of treatments and properties of which individual intensive care patients with COVID-19 leads to the best outcomes. This is done using machine learning, an important form of artificial intelligence, which is applied to large amounts of data from intensive care patients with COVID-19 from around 50 collaborating hospitals. The project is supported by the Dutch Association for Intensive Care and the National Intensive Care Evaluation Foundation.",,2023,Amsterdam UMC Locatie VUmc,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Prognostic factors for disease severity | Supportive care, processes of care and management",2020 +P29664,1.043E+13,Caging the dragon: translational approach to unravel and prevent COVID-19 associated thrombosis,"In COVID-19 patients, the number of cases of venous thromboembolism (VTE), such as thrombosed leg or pulmonary embolism, is remarkably high, up to 48% in the ICU. The presence of VTE causes more serious illness and an increased number of deaths. In addition, VTE occurs despite preventive treatment with blood thinners (heparin). This may indicate heparin resistance or the possibility that treatment with heparin is not the (only) solution. Finding the best possible treatment for COVID-19 patients requires understanding the disease process and risk factors, as well as the safety and efficacy of currently prescribed thromboprophylaxis and treatment. Research The study will study the exact number of VTE cases in the Netherlands and the effect of preventive treatment with heparin, identify risk factors and predict which factors contribute to this. Laboratory research also provides insight into the development of VTE. To distinguish whether VTE in COVID-19 patients is the result of a direct effect of the virus or indirectly via the immune system, a combination of clinical cohort studies with in-depth in vivo and in vitro studies is performed. To predict the risk of VTE in admitted COVID-19 patients, patient data are collected and VTE patients are identified. Dynamic prediction models are developed and individual VTE risks are estimated. COVID-19 patients will be monitored for the long-term effects of lung and heart function, functional status and quality of life. The project is carried out by the Dutch COVID & Thrombosis Coalition consortium . All UMCs and Sanquin participate in this. In addition, we collaborate with several general hospitals. The research is partly financed by the Netherlands Thrombosis Foundation.",,2025,Erasmus Medisch Centrum,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility,2020 +P29665,1.035E+13,Florence Remains Active in Corona Time,"Due to the closure of the nursing homes, almost most of Florence Actief's activities have been halted. This puts pressure on the most important objective of the Active philosophy: promoting and stimulating well-being in order to enable people over 60 to live at home in a healthy way (longer) for as long as possible. By seeking cooperation with on the one hand sectors that are hit hard by the Covid crisis and, on the other hand, by literally looking for the space to carry out our activities in a responsible manner, we think we can get an important part of our participants ""Active"" again.",,2021,Florence,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29666,1.043E+13,Ethnicity and COVID-19: epidemiology and control measures,"Our study shows that people with a migration background in the Netherlands are disproportionately affected by the coronavirus. In these population groups (during the first and second waves), the number of deaths due to COVID-19 per 100,000 people was 1.7 times higher than in the population of Dutch origin. During the second wave, infections in these groups were two to four times higher. They were also admitted to hospital relatively more often. However, once admitted, the health outcomes (ICU admissions, mortality) were comparable for different groups. We also showed that willingness to vaccinate at the beginning of 2021 was lower among groups with a migration background. Finally, these groups have been hit harder by the preventive measures, in terms of an increase in unhealthy behavior, reduced access to non-COVID care, and a decrease in mental health.",,2021,Amsterdam UMC - locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease susceptibility | Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2020 +P29667,1.043E+13,Evidence-based effective monitoring and control of Covid-19 after the initial outbreak,"In this one-year project, 14 groups of epidemiologists, medical researchers, mathematicians, physicists and psychologists from 10 institutions worked together on problems related to the fight against the coronavirus. New methods have been developed to create better models, for example by taking into account travel behavior and regional differences. Besides, there are methods have been developed to better map risk behavior. A large number of relevant questions for corona policy have been studied. Examples are: the effectiveness of contact tracing, the contribution of the CoronaMelder app, mass testing as a means to significantly reduce measures in society, safe ways to organize events, effects of opening or closing schools, the most effective way to limit spread in hospitals and ways to make restaurant visits possible with efficient testing. The results are recorded in 27 scientific articles, all of which will be freely available and largely already are.",,2021,Universiteit Utrecht,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2020 +P29670,1.043E+13,The impact and consequences of the restrictive measures following the COVID-19 outbreak for fertility patients and patients with endometriosis in the Netherlands.,"Objective A questionnaire was used to investigate the effect of the COVID-19 pandemic with the temporarily changed care provision on fertility and endometriosis patients. Results The study showed that fertility patients, endometriosis patients and their care providers found telephone and video consultations to replace regular physical consultations a good alternative during the first peak of the COVID-19 pandemic, but they did not consider it a good replacement for physical consultations in the future. Fertility patients experienced an increase in stress due to the temporary suspension of their treatment, and their quality of life was also lower than in a reference population from the past. Previous research has shown that stress levels can be negatively influenced by a feeling of helplessness, reduced control and support. A smaller increase in stress was reported in endometriosis patients. We advise care providers to be alert to an increase in stress, especially in fertility patients, and to pay attention to providing information.",,2020,Amsterdam UMC - locatie VUmc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Women,Caregivers | Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2020 +P29671,7430020682,Bright Minds for Covid-19,"Empowering young people during the corona crisis, that was the goal of Bright Minds before Covid-19. Young people worked in teams to answer questions for help and helped with initiatives from social organizations such as Neighborhood Meals, Corona Meldpunt Merenwijk, De Oudertelefoon and Praat Nederlands met me. They followed an online training program that allowed them to immediately apply new skills. Coordinators, volunteer mentors and peers guided them in this. The young people are grateful that they have been able to make themselves useful, have gained practical social experience and expanded their professional network. Initiators felt supported and inspired by the voluntary efforts of the young people. It also helped them get a better picture of their network.",,2021,Starters4communities,,Human Populations,Unspecified,Adolescent (13 years to 17 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Community engagement | Social impacts,2020 +P29672,838002502,Medicatiegesprek.nl,"Medication discussion Elderly people who use more medicines are at high risk of being hospitalized due to an error in the use of medication. To prevent this, the GP and pharmacist conduct medication discussions. The patient, GP and pharmacist come together to discuss the medication and adjust it if necessary. Problem Due to COVID-19, these three-way conversations are canceled, which increases the risk of elderly people being admitted to hospital due to medication errors. Solution We want to start these conversations again. This can be done using video calling. But existing solutions for this are not usable: not every elderly person has a telephone or tablet and installing an app is difficult. With this project we safely use open source software and 4G tablets to make video calls with the elderly. The pharmacy delivery person brings a cleaned tablet to the elderly person's home. The pharmacist can then start the connection with the elderly and the GP remotely and the three-way conversation can take place.",,2021,Apotheek Orion,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,Digital Health,,,,,Health Systems Research | Clinical characterisation and management,"Health service delivery | Supportive care, processes of care and management",2020 +P29673,1.01501E+13,RECoVERED,"In the RECoVERED study, almost 350 patients with mild to severe Covid-19 are being followed long-term to better understand how the immune system against the virus develops and responds to vaccination after infection, what the risk is for long-term complaints ('long Covid'), what complaints these are and why they arise. Findings so far show that, due to built-up immunity after infection, a single vaccination produces an excellent antibody response, even better than after 2 vaccinations without a previous infection. It has also become clear that long-term complaints, especially fatigue and shortness of breath, are common after experiencing Covid-19, even after mild infections, but that the risk of this is greater the more serious the infection was. An extensive search is currently underway for possible causes of 'long covid' complaints using collected data and blood samples. Results from this will hopefully allow us to better combat the long-term effects of COVID-19. The RECoVERED study is carried out by Amsterdam UMC - location AMC, Erasmus MC and GGD Amsterdam. Read more on the Amsterdam UMC website . More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2021,Amsterdam UMC - locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2020 +P29674,5460010031,Cooling solutions for (COVID-19) healthcare workers,"COVID-19 healthcare staff wear protective clothing such as a plastic apron, face mask, hairnet and splash goggles to prevent contamination with the coronavirus in the workplace. Although effective, this protective clothing limits the release of heat to the environment, causing many COVID-19 healthcare workers to experience heat stress. The COOLVID project ""Cooling solutions for (COVID-19) healthcare workers"" is a spin-off of the Thermo Tokyo project and aims to translate and implement knowledge and expertise about the use and application of cooling strategies from top sport to the healthcare sector . We specifically focus on nursing staff. Applied cooling interventions can substantially reduce heat stress, improving the physical and cognitive performance of healthcare professionals and reducing recovery time after a work shift. The research is carried out by Radboud University Medical Center in collaboration with TNO, Inuteq and NOC*NSF. What is the added value of cooling vests for healthcare professionals who work with COVID-19 patients? Thijs Eijsvogels and Boris Kingma investigated this with this research. They talk about it in the video. And nurse Mike Zwartkruis talks about the use of the cooling vests: 'I experience my work as much easier. You are less concerned with that heat, which ultimately allows you to provide better patient care.' Watch the project video. For practice: Cooling vest is part of standard equipment Special: COVID nurse gets through the shift better with a cooling vest",,2021,Radboudumc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Nurses and Nursing Staff,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2020 +P29675,1.01501E+13,Safety and efficacy of SARS-CoV-2 antibodies,"Severely immunocompromised patients, such as organ transplant recipients and patients with hematological malignancies, are at increased risk for severe coronavirus disease 2019 (COVID-19)-related morbidity and mortality. Plasma from COVID-19 infected individuals that contains antibodies that neutralize the virus can be used to treat those patients. However, our results from clinical and animal studies in which plasma was administered showed that the amount of neutralizing antibodies in the donor plasma and the time of administration are critical parameters for treatment effectiveness. In addition, resistance often occurred when monoclonal antibodies were used. Alternatively, we tested plasma obtained from individuals who received multiple COVID-19 vaccinations. Using in vitro assays, we were able to select those individuals with high levels of broadly reactive neutralizing antibodies against different SARSCoV-2 variants for plasma apheresis. These plasma preparations are now being tested in clinical trials to treat hospitalized severely immunocompromised patients. More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2021,Not available,,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management | Clinical trials for disease management",2020 +P29676,1.01501E+13,"Monitoring the evolution, spread and transmission of SARS-CoV-2 through whole genome sequencing to enable fast genotype to phenotype prediction","During this project we mapped the evolution and spread of SARS-CoV-2 in the Netherlands. We used this information in different phases of the pandemic: in the first phase we used it to estimate the extent of the pandemic in the Netherlands, then we mapped the evolution of the virus in mink and attempted to control the spread of to contain the virus between mink farms. In the current phase of the pandemic, we are looking at reinfections and viral evolution in patients infected with SARS-CoV-2 for a long time. Collectively, these findings have contributed to increasing our knowledge regarding the course of the pandemic and these results can be used to be better prepared for future variants and a faster translation between the findings in the lab and the possible impact of these findings to decide. Interim results This project has so far delivered the following interim results: - An article about transmission across national borders at the beginning of the COVID-19 pandemic in Limburg. - An article (still under peer review) on tracking SARS-CoV-2 variants B.1.1.7 (British variant) and B.1.351 (South African variant). - An article about the effect of vaccines on SARS-CoV-2 variant B.1.1.7 (British variant) and B.1.351 (South African variant). More information about research into corona and COVID-19 at www.zonmw.nl/coronaonderzoek",,2022,Erasmus MC,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2020 +P29677,1.01501E+13,ANAkinra for the treatment of CORonavirus infectious disease 2019 in the Intensive Care Unit (ANACOR-IC),"COVID-19 is associated with an intense inflammatory response, especially in the sickest patients in Intensive Care. These patients therefore also have more thrombotic complications. Some successful therapies have been found, all of which reduce inflammation, thereby reducing mortality from COVID. However, it is not known whether there are subgroups of patients who respond better or less well to these therapies, or what the effect of these agents is on thrombosis; nor on the specific clotting mechanisms that lead to thrombosis. This project investigated the effect of various interventions on the immune system and the coagulation cascade. Results are important to be able to provide the right therapy to the right patient and to better understand the occurrence of thrombosis during intense inflammatory reactions. More information Read more about research into corona and COVID-19 UMC Utrecht: groundbreaking new treatment for seriously ill corona patients",,2022,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P29679,1.01501E+13,Social Impact of Physical Distancing on Vulnerable Populations during COVID-19,"To reduce the spread of COVID-19, it is important to maintain physical distancing and stay home. What are the consequences of these measures for socially vulnerable groups who are already threatened with social exclusion? In this study during the first corona wave (March - July 2020), we looked at the impact among the elderly, people with mild intellectual disabilities, the homeless, families with young children and where domestic violence is an issue, as well as supporting professionals. A total of 244 people were interviewed and questionnaires administered to independently living elderly people (1697 people) and elderly people, family and employees in nursing homes (n=2619). Results show a variety of experiences, from relative peace and a sense of social normality in solitude to a loss of perspective. We conclude that during epidemic disease outbreaks, care for these groups should be seen as essential social interaction, necessary to guarantee minimal quality of life. (First) results The following conclusion can be drawn from the analysis of the stories and figures: the impact of the corona measures on vulnerable groups in the Netherlands appears to be significant, even now that rules are being relaxed. The lockdown has been too rigorous and too long for some. During the lockdown, social contact was especially missed, but at the same time it brought peace to the vulnerable. After the lockdown, confusion and inequality arose. It is also concluded that government measures were too focused on preventing contamination and chaos in the ICUs, while other forms of safety should also have been included in the policy. In their final report, the researchers present a series of policy recommendations aimed at facilitating social contact, promoting meaning for society, making rules understandable and developing digital care. More about the results of this research? View the results page or go to www.coronatijden.nl . Executive parties University of Amsterdam, Trimbos Institute, Amsterdam University of Applied Sciences, Pharos, MEE NL, Vrije Universiteit Amsterdam and Ben Sajet Center.",,2022,Universiteit van Amsterdam,,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Infection prevention and control | Secondary impacts of disease, response & control measures",Restriction measures to prevent secondary transmission in communities | Indirect health impacts,2020 +P29680,1.01501E+13,Kids and SARS-CoV-2 transmission and disease (CoKids-study),"Within the CoKids study, we investigated the occurrence of SARS-CoV-2 and other respiratory infections in 307 families with children in different age groups. The family members have been regularly tested for the coronavirus regardless of complaints. When a family member tested positive, or when he/she developed respiratory symptoms, a period of intensive monitoring of the entire family followed for 3-6 weeks. The spread of the coronavirus has been mapped by sampling family members, blood tests and daily registration of health complaints. This revealed that: 1) children experience a SARS-CoV-2 infection more often than previously thought based on previous registration data; 2) the symptoms and severity of SARS-CoV-2 infection in children are indistinguishable from other common respiratory infections; 3) children play a major role in the spread of SARS-CoV-2 within households; Young children in particular are more likely to pass it on to their parents. This probably has to do with the type of contact (care, cuddling) where maintaining distance is not possible.",,2022,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease susceptibility | Disease pathogenesis,2020 +P29681,1.01501E+13,Infection prevention of COVID-19 in hospitals: Control of COVID-19 iN Hospitals (COCON study),"In June/July 2020, antibodies against the novel coronavirus were detected in 15% of employees of 13 Dutch hospitals, indicating a history of infection during the first months of the pandemic. During the summer months, the coronavirus was less active and only 1% of employees experienced an infection. Antibodies were more frequently present in employees in Noord-Brabant and in employees working in the emergency department. Antibodies were less frequently found in employees in intensive, high and medium care, in employees with a lung disease and in smokers. Only 85% of employees with a history of infection had complaints. The most common complaints were severe fatigue, fever and coughing. In order to gain insight into the role of contamination of the patient's environment in the transmission of the novel coronavirus to healthcare workers, a study was also conducted in nursing homes. In the rooms where infected clients were in isolation, the coronavirus was frequently found in the immediate vicinity of the client. In addition, viable coronavirus was detected in one air sample. This indicates that airborne particles containing the novel coronavirus can be infectious.",,2022,Universitair Medisch Centrum Utrecht,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Hospital personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Infection prevention and control,IPC in health care settings,2020 +P29682,1.01501E+13,"Behavioral scientific research into perceptions, behavior and well-being of citizens during the Corona pandemic. Knowledge integration of COVID-related research in the field of prevention, care and broad social issues","Making visible to policymakers how citizens deal with the Corona behavioral measures over time. By having more than 50,000 Dutch people complete a questionnaire every 3 weeks about the measures announced by the government, support and well-being, it was made clear in the period April - July 2020 how citizens follow the measures, what they find difficult about them, how much support there is for showing the desired behavior and how the measures affect their sense of well-being. In addition, interviews were held with some of the participants in the questionnaire study and with groups that are less visible in the study, to better understand how they deal with the behavioral measures. We also looked at how the measures are discussed on social media. The study, which was conducted by the RIVM and the GGDs together (and continued after July), provides information on how citizens are doing over time and why it is that way. And thus provides insight into how to help people continue to follow the behavioral rules. This information supports policymakers who determine the measures for pandemic control and those who organize government communication. Through effective government policy and communication, the virus can be better controlled. More information about this research and other activities of the Corona Behavioural Unit of the RIVM can be found at www.rivm.nl/gedragsonderzoek",,2020,RIVM,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2020 +P29684,1.043E+13,Prospective cohort study of non-hospitalised COVID-19 patients: determining length of isolation and patient clinical development at home (COVID-HOME study),"The UMCG is conducting research among COVID-19 patients who are not admitted to a hospital and their family members. The researchers want to gain more insight into the impact and consequences of the disease on these patients and their families, in order to create guidelines for the treatment of COVID-19 patients at home. The necessity and importance of this research is great in the current phase of relaxing all measures and the possible new outbreaks that result. Goal More knowledge is needed to properly treat patients isolated at home and to improve guidelines. With this study, researchers want to gain more knowledge about how the disease progresses in this group of patients. The knowledge can help to provide patients with the right treatment in the future and to be able to determine in time when their condition will worsen. Greater insight into the contagiousness of these patients will help determine how long they should remain in isolation and when they can leave their home without the risk of transmitting the virus to others. Research design Persons who test positive are visited at home weekly to obtain clinical and laboratory data. This is done by, among other things, taking a nose/throat swab (cotton swab) and blood. To see whether the virus spreads through other routes, urine, feces and semen or vaginal swab are also collected. Nasal and throat swabs are also taken from family members of people who have tested positive to determine if and when they become infected. Executive parties The necessity and importance of this research is great in the current phase of relaxing all measures and the possible new outbreaks that result. The research is carried out in collaboration with the GGDs.",,2021,University Medical Center Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2020 +P29685,859003002,Programma COVID-19,"Goal The aim of this program is to improve specialist medical care in the context of the COVID-19 epidemic. This concerns (after)care for patients with COVID-19, but also bottlenecks that may arise for other patient groups. Activities All activities of this program fall under the Framework Letter Foundation Quality Funds for Medical Specialists 2. The activities within the program are divided into 2 program lines: Activities aimed at sharing knowledge and describing good care: sharing knowledge between experienced experts developing questions from scientific associations that lead to evidence-based positions drawing up, standardizing, sharing and maintaining protocols/guidelines/guidelines developing patient information (GP) Other activities that contribute to improving care: supporting materials for care provision in practice adjusting quality registrations knowledge agendas materials for further training and peer support",,2022,Stichting Kwaliteitsgelden Medisch Specialisten 2,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2020 +P29687,452020226,Stabilized Lassavirus glycoprotein trimers for next-generation Lassa fever vaccines.,Not available,,2023,The Scripps Research Institute,,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Arenaviridae,,,,,,,,,Lassa fever,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",,2021 +P29688,1.043E+13,"Vaccination of healthcare workers: 'four vaccines, four VOCs'. A comparative study of antibody production by 4 different SARS-CoV-2 vaccines against the different VOCs in healthcare workers.","The coronavirus (SARS-CoV-2) has changed since the first time the virus arrived in the Netherlands. New variants of the virus can more easily break through the protection of vaccinations or immunity from previous infections. It is therefore very important to know how the four vaccines used in the Netherlands perform against virus variants that we currently know, in order to prepare ourselves as best as possible for the future. That is why we determined the immunity (amount of antibodies) in 165 hospital employees. These people had previously been vaccinated with one of the four corona vaccines (BNT162b2 (Pfizer), mRNA-1273 (Moderna), AZD1222 (AstraZeneca) or Ad26.COV2.S (Janssen)). These employees had not previously experienced a corona infection. The results showed that the level of protective (neutralizing) antibodies was highest in subjects vaccinated with mRNA-1273 (Moderna), followed by subjects vaccinated with BNT162b2 (Pfizer). Persons vaccinated with AZD1222 (Astra Zeneca) or Ad26.COV2.S (Janssen) had the lowest numbers of antibodies. The antibodies had a much less neutralizing effect against the new Omicron variant than against the original coronavirus. If these people subsequently received a booster vaccination with BNT162b2 (Pfizer), the antibodies clearly increased, even when it comes to new variants such as Omicron. What was striking is that the effect of the booster vaccination was the least good in people who were originally vaccinated with AZD1222 (Astra Zeneca).",,2022,Amsterdam UMC - locatie VUmc,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +P29689,1.043E+13,SamenSlimOpen - Data-driven Simulation Games for the Evaluation and Prevention of SARS-CoV-2 Transmission in Indoor Public Spaces and the Impact of Changing Compliance to Distancing Measures,"Public indoor spaces are an important source of corona infections. Therefore, many measures are aimed at preventing infections in these spaces. In order to investigate which types of contacts in indoor spaces contribute most to the spread and how this can best be intervened, a virus spread model has been developed that models the behavior of people in indoor spaces in the presence or absence of measures and with different degrees of compliance. The models are informed by virological, epidemiological and crowd monitoring data. We have estimated where high-risk contacts occur in different types of spaces (restaurants, offices, train stations), which infection routes play the most important role in this and which measures are most effective in limiting infections, while maintaining economic activity. In addition, the model has been used to investigate the effect of different corona access cards, how this depends on the epidemiological situation as well as the degree of compliance in society.",,2023,Wageningen University & Research,,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P29690,1.015E+13,Risk assessment for zoonotic transmission of avian influenza in the Netherlands,"Zoonoses pose a serious threat to public health. Examples include SARS-CoV-2 and avian influenza viruses. For optimal prevention and control, it is important to identify which animals and humans are at risk of infection, so that monitoring and surveillance can be optimised. Aim This project focuses on a quantitative risk assessment for transmission of avian influenza viruses from waterbirds, via captive birds, to humans. Approach/working method We use an integrated approach, with a risk stratification of large- to small-scale animal holdings, while taking differences in species, numbers, geographical distribution, risk, type and duration of contact with humans into account. In the first part, data on risk populations is collected and analysed statistically. These analyses are subsequently extended using transmission models to quantify the impact of interventions such as vaccination or biosecurity measures.",,2028,Universitair Medisch Centrum Utrecht,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2024 +P29691,1.071E+13,Data preparedness of the Amsterdam Cohort Studies,"Long-term cohort studies provide a solid foundation for rapidly answering urgent research questions during a pandemic, as they have a well-structured research framework and relevant pre-pandemic data. An example of this is the Amsterdam Cohort Studies (ACS), which have been studying men who have sex with men in Amsterdam for 40 years. Originally designed to investigate the HIV epidemic, this study has again proven to be able to quickly make valuable contributions to pandemic research for both the SARS-CoV-2 virus and the monkeypox virus.",,2024,GGD Amsterdam,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities | Other,Unspecified,Non-Clinical,,Coronavirus | Poxviridae | Novel Pathogen,,,,,,,,,COVID-19 | Mpox | Disease X,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Data Management and Data Sharing,,,Netherlands,,Epidemiological studies,,2024 +P29692,1.04304E+13,"SARS-CoV-2 and other virus infections; interference, synergy or both?",The coronavirus continues to circulate in our society. Little is known about how corona and other respiratory viruses will circulate together in the future and what the effects of this will be.,,2024,Universitair Medisch Centrum Utrecht,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus,,,,,,,,,COVID-19 | Other,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease transmission dynamics",2023 +P29693,1.04302E+13,"HepaPuff, an innovative handheld heparin nebuliser to prevent infection with SARS-CoV-2 and new emerging respiratory viruses.","(Hepa)Puff against new virus pandemics Researchers from the Amsterdam UMC and UvA, together with the company Medspray, will develop a Heparin hand nebulizer that not only protects against coronaviruses but also other viral respiratory infections. They combine an innovative hand nebulizer based on nanotech membrane chip technology with a broad spectrum virus inhibitor. The nebulizer will not only be tested on in vitro models but also in healthy volunteers in a controlled environment. Because clinically approved inhibitors and an existing new technology are used, the so-called HepaPuff can be brought onto the market quickly after completion of the project. HepaPuff will be an accessible and affordable prevention method against SARS-CoV-2 variants and possible new virus pandemics.",,2026,Amsterdam UMC Locatie AMC,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,Innovation,,,Netherlands,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2023 +P29694,1.04304E+13,SamenSlimOpen - Sector-specific inventory of spread risks in indoor spaces and the impact of measures in a changing epidemiological situation,"Public indoor spaces play an important role in the spread of SARS-CoV-2 and other respiratory viruses (respiratory tract infections). For this reason, many measures are aimed at preventing or reducing infections in indoor spaces. The SamenSlimOpen consortium has developed a model with which the behavior of people in indoor spaces and the associated risks of virus spread can be modeled. We have used this model to calculate the effect of proposed measures in indoor spaces for 5 sectors (catering, retail, higher education, culture, sports). The results of this project provide policymakers within government and sectors with insight into which (combination of) measures are most effective in different areas, and how this depends on the epidemiological situation (virus pressure, vaccination rate).",,2023,Wageningen University & Research,,Human Populations | Environment,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2022 +P29695,1.043E+13,Aerogenous spread of SARS-CoV-2 in social situations and during medical procedures.,"Goal To understand which measures help to limit the spread of the Coronavirus, knowledge is required about the routes of spread. Traditionally, it is thought that viruses that cause respiratory complaints spread through large droplets. These large droplets can infect someone by coughing directly, but can also spread by hitting a surface. The role of aerosols (the very small droplets) has only been studied to a limited extent. Results This study investigated whether we could detect 'live' virus in air samples taken from more than 2 meters from a positively tested person. In approximately one third of the people, at least 1 (out of a maximum of 2) sample(s) was positive at a distance of more than 2 metres. The virus culture subsequently showed that the viruses in these samples were still able to infect human cells. Follow-up research will have to demonstrate whether the amount of virus in these aerosols is sufficient to actually lead to infection.",,2021,Universitair Medisch Centrum Groningen,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Netherlands Organisation for Health Research and Development (ZonMW),Netherlands,Europe,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2020 +P29784,,"Strengthening global and regional health security through surveillance of emerging Poxviruses in humans, domestic and peri-domestic animals, and wildlife Dr. David Kelvin Dalhousie University RNS Funding Contribution: $250,000 Total Project Value: $850,000 Funding Partners: Canadian Institutes of Health Research, African Institute of Mathematical Sciences Key Words: ecological, zoonotic, interventions and risk management, public health, monkeypox virus, zoonotic viruses, wastewater https://researchns.ca/2023/06/19/research-nova-scotia-invests-250k-in-dalhousie-university-research-team-for-emerging-poxvirus-surveillance/","ecological, zoonotic, interventions and risk management, public health, monkeypox virus, zoonotic viruses, wastewater",,-99,N/A,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Research Nova Scotia,Canada,Americas,,,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease surveillance & mapping,2024 +P29893,897666,A Comprehensive Supramolecular Approach for an RNA vaccine for Influenza A (H1N1),"*The development of vaccines is key for disease prevention, and is a major focus globally in the healthcare sector. Seasonal influenza is an acute respiratory infection caused by influenza viruses which circulate in all parts of the world. Seasonally, it remains a persistent health threat and has been declared an epidemic in some states. Typical vaccines have been less effective against rapidly evolving pathogens such as influenza. A new class of vaccines based on nucleic acids, namely RNA, have recently been developed and show immense promise due to their robust nature, short manufacturing times and enhanced efficacy. Here we propose an RNA delivery system based on a supramolecular assembly approach for the vaccination of influenza A H1N1 strain. Specifically, a π-amphiphile will be used as the platform molecule for covalent RNA conjugation and delivery. A messenger RNA (mRNA) targeting the hemagglutinin (HA) gene from a model influenza virus strain will be employed as the therapeutic (H1N1/PR8-HA). The central π-amphiphile moiety will be functionalized with the mRNA strand via a redox responsive disulfide bond, and hydrophilic oligo-oxy aryl groups connected via a hydrogen bonding unit to promote self-assembly. Steric stabilization will be afforded to the surface decorated mRNA to protect from enzymatic hydrolysis in the complex biological environments, through co-assembly with an analogue π-amphiphile which has been alternatively decorated with poly(ethylene glycol) (PEG) chains. Efficient intracellular transport of the delivery vehicle to achieve optimum mRNA transfection will be achieved through the incorporation of a TAT-peptide on the PEG chain end. The therapeutic efficacy of the nanoassembly will be evaluated through transfection efficacy in macrophage cell lines. Overall, this proposal aims to lay the groundwork for extending the scope of RNA vaccines by exploring the potential of supramolecular assemblies as a delivery vector.",,2022,THE UNIVERSITY OF BIRMINGHAM,231075.72,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,United Kingdom,,"Vaccines research, development and implementation",Pre-clinical studies,2020 +P29894,101151817,Bridging epidemic modelling and phylogenetic methods to understand avian influenza transmission in poultry trading networks,"Poultry production has risen as the main livestock sector worldwide, with this growth being primarily driven by low and middle income countries such as Bangladesh. Unfortunately, the high circulation of avian influenza in domestic flocks undermines economic and societal benefits of poultry production in this country and raises significant concerns for human health. Nonetheless, avian influenza transmission in Bangladeshi poultry remains poorly characterised. To fill this gap, the EPHYFLU project will shed light on the transmission patterns of H9N2 avian influenza virus, the most common strain in Bangladesh, by combining state-of-the-art mechanistic models and high quality sequence data. In particular, this project will develop novel methods to leverage genomic data to inform epidemic models, which will be used to assess the effectiveness of a range of veterinary public health interventions aiming to reduce H9N2 avian influenza transmission. This program will result in novel policy recommendations for avian influenza control in Bangladesh, and contribute to the integration of phylogenetic and mechanistic modelling.",,2026,"INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT",211754.88,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Impact/ effectiveness of control measures",2024 +P29895,101081818,Glycoengineered erythrocytes for better influenza vaccines,"The objective of this ERC PoC project is to establish technical and commercial feasibility of our recently developed glycan-engineered red blood cells (RBCs) for antigenic characterization of circulating influenza A/H3N2 viruses. Due to the rapid evolution of influenza A/H3N2 viruses, antigenic characterization by the widely used hemagglutination inhibition (HI) assay is not possible anymore. Continuous antigenic characterization of influenza A viruses is, however, essential for the development of protective seasonal vaccines. The ERC program ""sugar-enable"" has developed glycoengineered RBCs that make it possible again to antigenically characterize circulating A/H3N2 viruses by the standard HI assay, and it is expected that the cells will find application in hundreds of laboratories worldwide.",,2024,UNIVERSITEIT UTRECHT,149790,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H3,,,H3N2,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Netherlands,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Supportive care, processes of care and management",2022 +P29896,882631,Deciphering the unconventional receptor binding and modulation activity of bat influenza A viruses,"Influenza A viruses (IAVs) are zoonotic pathogens that frequently cross the species barrier into humans, often causing severe morbidity and even global pandemics. This cross-species transmission is facilitated in large part by alterations in the interaction between the viral surface proteins hemagglutinin (HA) and neuraminidase (NA) and sialic acid, a ubiquitous glycan that serves as the cellular entry receptor. Although avian hosts have generally been thought to be the primary reservoir for all influenza A viruses, this dogma has recently been challenged by the identification of two novel IAV subtypes in bats, H17N10 and H18N11. Despite an otherwise high degree of functional homology to conventional IAVs, the surface proteins of bat IAVs demonstrate several unprecedented characteristics. Specifically, these proteins are unable to interact with sialic acid; rather, we recently showed that bat IAVs use the major histocompatibility complex class II (MHC-II) protein to gain entry into host cells. Unexpectedly, we observed that N11 downregulates surface expression of MHC-II, suggesting that it potentially harbors a receptor-destroying function. Most surprisingly, bat IAV could replicate to even higher titers the absence of functional NA, a capability which has never been observed among influenza viruses. These findings suggest that the surface glycoproteins of bat IAV may possess a structural plasticity that is much broader than that of conventional IAV. In light of the critical importance of the surface proteins for cross-species transmission of IAV, the goal of this project will be to probe this plasticity, first by determining the mode of interaction between H17/H18 and MHC-II and elucidating the mechanism of N10/N11-dependent downregulation of MHC-II, but most importantly by using forced evolution to explore the plasticity of IAV for new cellular entry factors. The insights from these studies will have a major impact on our understanding of influenza virus tropism.",,2025,UNIVERSITAETSKLINIKUM FREIBURG,2957571.09,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Germany,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P29897,843470,Spatial and demographic dynamics of disease transfer at the wildlife-human interface,"Infectious diseases present a significant and growing threat to public health, domestic livestock production, and biodiversity conservation. Due to their global distribution and wide-ranging movements, seabirds are important vectors for the spread of pathogens across continents and ocean basins. Coastal seabirds, which associate with and exploit anthropogenic food sources, are particularly likely to interact with human-associated pathogens and zoonotic agents, making them useful candidates for monitoring disease prevalence. However, many factors mediating the interactions between seabirds and pathogens remain unknown or poorly understood. Our study will combine targeted field data collection, laboratory analysis, and quantitative modeling to develop a mechanistic understanding of the factors affecting prevalence and transmission of infectious diseases by seabirds at the wildlife-human interface. We will explore spatial and demographic factors affecting exposure and transmission rates for two key zoonotic diseases, toxoplasmosis and avian influenza, by a generalist coastal seabird, the yellow-legged gull (Larus michahellis) in the western Mediterranean basin. Within this study system, we will combine movement analysis using biologging, serological sampling, habitat and demographic analysis, and agent-based models to develop a comprehensive understanding of epidemiological dynamics. We will also use experimental studies to directly test the development of disease immunity in nestling birds and the effects of management actions on disease transfer. We will then apply scenario planning to study the effects of both management and habitat change on disease dynamics. Our results will not only improve understanding of gulls as vectors for infectious agents, but also provide a comprehensive quantitative framework for modeling disease dynamics that can be adapted to predicting and managing the spread of infectious disease at the wildlife-human interface.",,2022,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS,219388.25,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,France,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Vector biology | Animal source and routes of transmission | Disease transmission dynamics | Disease susceptibility,2020 +P29898,856581,Ubiquitin Chains in Viral Infections,"Viruses such as Influenza A (IAV) and others remain one of the greatest threats to human health and society. Despite their danger and widespread prevalence, the molecular mechanisms of how they infect mammalian hosts and evade the immune system remains poorly understood. Recent studies from our team implicate two common proteins - HDAC6 and unanchored ubiquitin chains - in host cells as key mediators of viral entry via the aggresome processing pathway. This discovery offers a new line of investigation for understanding and preventing viral infections. By identifying the pathways and interactions involved in this infection process, we will provide new molecular targets for the development of broad-spectrum antiviral compounds. Multidisciplinary studies by a team consisting of a molecular biologist, a virologist, and a chemical biologist will use a diverse set of tools to validate these pathways and gain fundamental knowledge about their regulation. To achieve this, detailed studies on the exact nature of the ubiquitin chains needed to activate HDAC6 will allow the development of biochemical and cellular assays of Influenza A infection and enable the determination of the precise mechanism and the downstream cellular pathways necessary for viral infection. The chemical synthesis of labeled ubiquitin chains will support detailed structural studies and a clear understanding of how they are formed and packaged into infectious viral particles. The strong possibility that numerous other virus types also utilize this pathway will be tested with life-threatening agents of current concern including Zika, Dengue, Ebola, and MERS viruses. By demonstrating - with both biological approaches and small molecule compounds - that blocking these cellular processes in cells and animal models reduces viral infection, this project will provide a wealth a novel insights and the basis for the development of a new generation of anti-viral therapies.",,2026,FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION,8292435.23,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae | Orthomyxoviridae,Unspecified,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Zika virus disease | Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P29899,949506,Post-transcriptional regulation of influenza A virus RNA,"This research proposal aims to significantly alter our understanding of the critical role post-transcriptional processes play in the influenza A virus (IAV) life cycle. Post-transcriptional regulation of cellular mRNAs has seen a lot of research interest in recent years, including projects looking at the effects of RNA modifications and ribosome specialisation. However, much less attention has been paid to the effects these processes have on the viral life cycle. This project focuses on the post-transcriptional regulation of both IAV mRNAs and negative strand vRNAs. However, outcomes of this work will have a profound effect on our perceptions of the regulatory processes affecting a wide range of viral RNAs. In fact, by better understanding the roles of these processes on viral RNAs, such as IAV, we can also uncover novel functions on cellular mRNAs. This project comprises 5 work packages with 11 intermediate goals. We will first identify the locations of various modifications present on IAV RNAs across multiple strains in both human and avian infected cells, significantly expanding on our current understanding, while exploring the potential for species-specific adaptions. Through mutagenesis and RNA capture techniques, we will evaluate how these modifications affect RNA characteristics and what effector proteins are involved in these processes. We will also use this information to determine the composition of ribosomes actively translating IAV mRNAs and evaluate whether specialised ribosomes are involved in the normal IAV life cycle. Finally, we will focus on the roles of RNA modifications on vRNAs, which should be quite distinct from mRNAs, and the host proteins that specifically bind, or are blocked from binding, sites of modification. This is an ambitious, multifaceted project that will have a direct impact on our understanding of IAV biology, and also provide novel insights of value to multiple disciplines including virology, RNA biology and protein translation.",,2026,THE QUEEN'S UNIVERSITY OF BELFAST,1847742.98,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P29900,865819,AmplificatioN Free Identification of cancer and viral biomarkers via plasmonic nanoparticles and liquid BIOpsy,"The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available. By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells. At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.",,2026,POLITECNICO DI TORINO,3324577.1,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Italy,,Clinical characterisation and management,Prognostic factors for disease severity,2021 +P29901,883285,Pandemic Preparedness and Response,"PANDEM-2 implements and demonstrates the most important novel concepts and IT systems to improve the capacity of European pandemic planning and response. Following the PANDEM project (with the same coordinator and many shared partners) and extensive subsequent stakeholder engagement, research and prioritisation, PANDEM-2 meets the real-worPANDEM-2 implements and demonstrates the most important novel concepts and IT systems to improve the capacity of European pandemic planning and response. Following the PANDEM project (with the same coordinator and many shared partners) and extensive subsequent stakeholder engagement, research and prioritisation, PANDEM-2 meets the real-world needs of public health agencies responsible for pandemics ('pandemic managers') and first responders across Europe. PANDEM-2 will enable and demonstrate the capture and integration of pandemic-relevant data from international systems (Go.Data outputs, EWRS, TESSy, etc.), participative surveillance (Influenzanet, Studybugs, etc.), fron laboratory (next generation sequencing) systems and from social media (Twitter, Reddit). This data will be accessible and can be analysed via an online dashboard, designed and built to support the specific needs of pandemic managers. Additional high-priority tools for pandemic spread prediction, visual analytics and resources management, including workforce capacity mapping, will improve preparedness and planning, and enable pandemic managers to be as well positioned as possible for a pandemic when it comes. In order to test the system, while also networking and building relationships across borders and organisations, pandemic managers and first responders from multiple Member States will work together in EU-wise demonstrations, planning and responding to several pandemic scenarios, from Ebola to SARS/MERS CoV, to pandemic influenza. Pandemic communications, highlighted as a key capability gap, will be addressed by resource creation, training and evaluation.",,2023,NATIONAL UNIVERSITY OF IRELAND GALWAY,10546024.41,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Filoviridae | Orthomyxoviridae,Unspecified,,,,,,,,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS) | Ebola virus disease | Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Ireland,,,,2021 +P29902,842621,Digging deeper into genes to track infectious disease outbreaks,"Successful public and animal health interventions require detailed knowledge of infectious disease transmission dynamics, in particular how they spread within and between populations. Recent advances in phylodynamics have largely contributed towards the understanding of epidemic spread, including Ebola, HIV and MERS-CoV, by integrating epidemiological and genetic data. Since the beginning of the 21st century, the emergence of new avian influenza viruses (AIV) with high pandemic potential have underlined the need for established global mechanisms to respond to public and animal health threats. To this end, DIGDEEP aims at developing alternative control strategies tailored to the characteristics of AIV evolution and transmission in order to minimize the global economic and health impact of the epidemics. The project will use cutting-edge phylodynamic inference methods to explore devastating and unprecedented epidemics of AIV in Europe and Asia. The outcomes of the project will allow us to infer key epidemiological parameters of the virus spread, such as the basic reproduction number or the likelihood of spillover between host species, and characterize the determinants of the epidemics, such as the importance of population structure or super-spreaders. DIGDEEP will also help to assess the effectiveness of public and animal health interventions in bringing the epidemic under control which are crucial for a well-informed response. Throughout the project, the fellow will gain a strong experience in phylodynamic inference methods, complementing her experience in epidemiology of infectious disease transmission. DIGDEEP will consolidate her scientific expertise in the field of public and animal health and develop transferable skills in team-working, communication and project management, which will be paramount to boost her career as a successful and internationally-recognized researcher.",,2022,EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH,239838.23,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,European Commission,International,International,Europe,Unspecified,,,,Switzerland,,Epidemiological studies,Disease surveillance & mapping,2020 +P29940,ANRS0290,"Study of the persistence of the Monkeypox virus over time on different surfaces or materials, under different environmental conditions and validation of decontamination methods",N/A,,,CEA,154492.97,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,,,France,,"Pathogen: natural history, transmission and diagnostics | Infection prevention and control","Environmental stability of pathogen | Barriers, PPE, environmental, animal and vector control measures",2022 +P29941,ANRS0291,Pathophysiology of Monkeypox and antiviral screening models,N/A,,,Université de Poitiers (UR155560 LITEC),195749.5,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,Clinical characterisation and management,"Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course",France,,"Clinical characterisation and management | Therapeutics research, development and implementation",Disease pathogenesis,2022 +P29942,ANRS0292,Characterizing the spreading dynamics of 2022 monkeypox outbreak in France to aid public health policies,N/A,,,Institut Pierre Louis d'Epidémiologie et de Santé Publique (UMR1136),245033.71,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes,France,,Epidemiological studies,Disease transmission dynamics,2022 +P29943,ANRS0293,Infection by Monkey pox (MPXV) and male genital tract,N/A,,,IRSET (U1085),331634.73,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,Clinical characterisation and management,"Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course",France,,Clinical characterisation and management,Disease pathogenesis,2022 +P29944,ANRS0294,"Monkeypox social sciences: perception of risks, health measures and vaccination",N/A,,,Aix-Marseille Université (SESSTIM),214425.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,"Policies for public health, disease control & community resilience",Risk communication & community engagement e.g. key populations | Behavioural drivers of risk and protection in different contexts,France,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2022 +P29945,ANRS0295,"Monkeypox virus distribution, transmission, dynamics and immune response (MOVIDA): a substudy of the MOSAIC European Monkeypox observational cohort",N/A,,,Hôpital Pitié-Salpêtrière (U1136 iPLESP),582101.71,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes,France,,"Epidemiological studies | Pathogen: natural history, transmission and diagnostics",Disease transmission dynamics | Immunity,2023 +P29946,ANRS0296,One Health approach to document the extent of monkey pox viruses (MPXV) infections to evaluate frequency and risk for cross-species transmissions to humans in Africa,N/A,,,Universite de Montpellier (TransVIHMI),407036.55,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Africa,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Investigation of zoonotic transmission & reservoirs | Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including via various modes,France,Congo (DRC),Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics,2022 +P29947,ANRS0297,Seroprevalence of Monkeypox infection in HIV-infected patients and PrEP users,N/A,,,Hopital Pitié-Salpêtrière,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,Epidemiological studies,Epidemiology & transmission dynamics of mpox including sexual transmission. | Disease epidemiology & risk factors & modes of transmission | Ongoing assessment & evaluation of surveillance,France,,Epidemiological studies,Disease surveillance & mapping,2022 +P29948,ANRS0298,Preclinical evaluation of MVA as vaccine against monkeypox virus (MKPXV) experimental infection in cynomolgus macaques,N/A,,,Institut de Recherche Biomédical des Armées,309699.91,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Unspecified,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",France,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P29949,ANRS0299,Is MonkeyPox virus in domestic animal population from North of West-Africa endemic? first statements,N/A,,,Institut Pasteur,155333.94,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,Europe,Africa,,,,France,Guinea,Animal and environmental research and research on diseases vectors,,2022 +P29956,ANRS0576s,UNITY Monkeypox Trial,N/A,,,Instituto Nacional de Infectologia Evandro Chagas,169984,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,Agence nationale de recherche sur le sida et les hépatites virale [National Agency for AIDS Research] (ANRS),France,Europe,,Unspecified,,,,Brazil,,,,2023 +P29993,MR/Y03368X/1,Flu: TrailMap-One Health,"The world is as close as ever to the emergence of an influenza pandemic caused by an H5N1 influenza virus. This is a deadly bird flu virus and the current strain, known as clade 2.3.4.4b, has now spread across 5 continents, a geographically unprecedented distribution. The virus kills wild birds as well as poultry. The virus also appears to have additional environmental resilience in that it has survived over the summer in regions where bird flu does not normally persist outside of winter. More worryingly, wild mammals that have scavenged dead bird carcasses have been infected, often with fatal consequence. In the UK this includes foxes and otters, in the Americas, sea lions and other marine mammals. So far, only 11 people have been reported infected, but the virus has now found its way into farmed or domesticated animals including farmed mink in Spain, farmed foxes in Finland and cats in Poland. There is much higher and more frequent contact between humans and these animals compared to the wild scavengers or marine mammals, so the likelihood of more human infections, or 'spillovers', from exposure to an animal carrying the virus has increased. At the population level, we are also at risk that this bird flu mutates and gives rise to an epidemic or even a new pandemic. All previous influenza pandemics have originated from viruses that originally circulated in wild birds. Most avian influenza viruses, including this one, cannot immediately cause a new pandemic because they are not adapted for efficient replication in the human airway or for transmission through the air, even if they can infect humans. The pandemic influenza viruses of the last century have sometimes reached humans after infecting and mutating in an intermediate domestic mammal such as pigs. At times like this governments are faced with truly difficult decisions about how much time and money to invest in pandemic preparation for a particular strain. Should we stockpile antivirals and matched vaccines and invest in PPE, or wait and see what develops? In the early 2000s a different strain of H5N1 caused public health concern but never acquired the adaptive mutations to transform into a pandemic virus. Is this one any different? The virus in 2005 killed around 50% of the people it infected during spillover events. Because so few people have been infected as of yet by the current clade 2.3.3.4b H5N1 strain we don't really know how dangerous this virus is for humans and how severe a pandemic would be. To answer these questions, we need to compare the new virus to previous strains, to assess the susceptibility of intermediate animal hosts, and to understand the barriers for this virus to acquire further adaptation to humans at the molecular level. We propose to work as a consortium and take a multipronged approach to risk assess in depth the current clade 2.3.4.4b H5N1 avian influenza viruses for human spillover infection and pandemic potential. The contemporary viruses will be compared with those of the early 2000s, and with other influenza viruses that did cause human pandemics in 1968 and 2009. We will use state of the art approaches to study virus/host molecular interactions, and define how these vary with different isolates of the clade 2.3.4.4b virus and between different host species. We will consider the interactions the virus makes with the human airway from children and adults, to understand who is most likely to be infected by and transmit the virus and who is most at risk of disease. We will incorporate modelling approaches to inform surveillance, asking where and how the virus is most likely to infect mammals that could serve as intermediate hosts. We will develop systems by which mitigations such as antiviral drugs or vaccines could be assessed, if the virus were indeed to jump species.",,2025,Imperial College London,4242568.2,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,H5N1 | Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2024 +P29994,300037/Z/23/Z,Mathematical modelling to improve the efficiency of vaccine development pipelines.,"Vaccines are one of the major successes of public health, with modern laboratory techniques allowing the development of vaccines against a wide range of pathogens and speeding their development. Clinical trials (phases III and IV) are often costly and time consuming, acting as a bottleneck to the rapid deployment of vaccines. My project will consider how epidemiological models can be used to enhance the vaccine development pipeline, using five infections as motivating and well-understood case studies: SARS-CoV-2, respiratory syncytial virus, Rift Valley fever, Lassa fever and yellow fever. In this project I will develop a suite of sophisticated models, based on the known epidemiology of the infections and using early immunological data as strong priors on vaccine behaviour. These models will feed into pre-trial quantification of the infection dynamics, assessment of effective and efficient phase III trial design, and evaluation of the impact of deployment within the population. This will be supported by researchers working in vaccine trials and deployment within Kenya and across Africa.",,2029,Kemri-Wellcome Trust Research Programme,610260.1,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Bunyaviridae | Coronavirus | Flaviviridae | Other,,,,,,,,,Lassa fever | Rift Valley Fever | COVID-19 | Other,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Kenya,,"Vaccines research, development and implementation",Vaccine trial design and infrastructure,2024 +P29995,300262/Z/23/Z,Forging the path to rational design of synthetic homing endonuclease gene drive systems in Aedes aegypti,"The alarming escalation of disease caused by Aedes aegypti, the primary vector of dengue, Zika, and chikungunya viruses, presents a pressing challenge for Low-and-Middle-Income Countries (LMICs) and is strongly predicted to worsen with climate change affecting mosquito distribution. Despite the promise of the homing endonuclease gene (HEG) drive system as a powerful, low-cost genetic biocontrol method for this mosquito vector, a limited understanding of the underlying mechanism of the system has hindered rational design for systematic improvement of its efficiency. Therefore, my research project aims to bridge these gaps and optimise the HEG drive efficiency in Ae. aegypti to a level fit for field application. The project's key goals include the following: 1. Identifying homing-susceptible cell stages and associated regulatory elements 2. Developing tools for the strict regulation and multiplexing of sgRNAs/crRNAs 3. Optimising HEG drive efficiency in Ae. aegypti The achievement of these objectives will have significant implications for public health by enabling more effective control of mosquito-borne diseases. The tools will be developed in parallel and successful development will not only advance the field of Ae. aegypti genetic biocontrol, but also act as a model for the rational design of HEG systems in various other pest species.",,2029,University of York,911335.77,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Animal and environmental research and research on diseases vectors,Vector biology | Vector control strategies,2024 +P29997,303666/Z/23/Z,ISARIC 3.0: Strengthening the global clinical research ecosystem for epidemic and pandemic prevention and preparedness,"The International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) is a global federation of clinical research networks established in 2011. The purpose of ISARIC is to prevent illness and deaths from outbreak- prone infectious diseases. This is achieved by conducting clinical research to improve patients' care and facilitating a globally coordinated and agile research response to infectious disease threats. ISARIC's work programme for 2024-2029 is organised into 3 complementary platforms: clinical research, interoperability and acceleration, and capacity sharing and quality improvement. Ongoing clinical research will focus on acute respiratory infections, henipavirus disease, filovirus disease, and dengue. Through these clinical research programmes, a series of innovations will be pursued in data sciences, clinical trial designs, and research management. This ambitious work programme will generate clinically meaningful research evidence on the diseases of initial focus, whilst substantially improving clinical research readiness for emerging infectious disease threats through increased collaboration, improved interoperability, enhanced agility, and strengthened capabilities. The centre of gravity of the work will be low- and middle-income countries, and the capacity sharing and quality improvement platform will seek to empower local research leaders. Changes to ISARIC's governance will support ISARIC's goal to devolve responsibilities to ISARIC Hubs and enhance stakeholder engagement.",,2029,University of Oxford,7637307.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Filoviridae | Flaviviridae | Paramyxovirdiae | Unspecified,,,,,,,,,Ebola virus disease | Marburg virus disease | Nipah and henipaviral disease | Other | Unspecified,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Clinical characterisation and management | Health Systems Research,"Supportive care, processes of care and management | Clinical trials for disease management | Health service delivery | Health leadership and governance",2024 +P29998,226142/Z/22/Z,"West Africa, West Indies, West London: Mechanisms driving heterogeneity in immunity to SARS-CoV-2 variants","Our proposed WWW Consortium brings together three prospective cohort studies of healthy adults in receipt of COVID-19 vaccination in West Africa, the West Indies, and West London to answer fundamental questions in the immunology of SARS-CoV-2 variants. Given the diverse outcomes of COVID-19 in our respective locations, despite many overlapping characteristics such as shared genetic ancestry and AZD1222 vaccination, we have power to make a significant contribution to understanding the mechanisms underlying the apparent heterogeneity in our cohorts. We have 3 aims: - Harmonise our studies to determine the breadth of immunity to SARS-CoV-2 variants by transferring assay and modelling capacity between sites, while also genotype participants to enable comparison across our mixed-ancestry populations; - Test four hypotheses that may contribute to breadth within and between our cohorts: exposure to prior SARS-CoV-2 variants, to other bat & human coronaviruses, to malaria, and to host immunoreactivity; and - Build models of immune responses to variants that incorporating individual-level data and are applicable in LMIC settings with limited datasets. Together, our work will provide insights into the factors that drive the complex immunology to SARS-CoV-2 variants that can also inform future pandemic response in regions currently underserved by both research and surveillance capacity.",,2026,The Francis Crick Institute,3678389.73,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Characterisation of vaccine-induced immunity",2023 +P29999,220757/Z/20/Z,Malawi-Liverpool-Wellcome Trust COVID-19 Epidemic Preparedness,"Malawi is at high risk of COVID-19 epidemic spread, the healthcare system is fragile and the population vulnerable to severe disease. This application proposes Malawi Liverpool Wellcome Trust Clinical Research Programme preparedness activities for epidemic COVID-19 disease. These are split into three work packages: 1) Diagnostic capacity and genomics surveillance; 2) Secondary care; 3) Epidemiology and control. Strategically, we have designed our activities to develop a platform for MLW to rapidly pivot into response mode to both support the healthcare system and deliver excellent research for current and future epidemic disease threats. Key goals for this proposal are: - Provide diagnostic capability in Malawi for the COVID-19 epidemic - Develop clinical and epidemiological tools to manage epidemic disease in Malawi",,2021,Liverpool School of Tropical Medicine,153348.31,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Impact/ effectiveness of control measures | Supportive care, processes of care and management",2020 +P30000,227766/Z/23/Z,Working on the Edge: Examining the Gendered Health Implications of Precarious Employment and Job Insecurity among Palestinian Workers,"Precarious employment is a global issue that negatively impacts physical and mental health and disproportionately affects disadvantaged populations such as women, young people, and refugees. In Palestine, underemployment and unemployment rates are high, particularly among young people and women who often work in the unregulated industry without social security, making them vulnerable to exploitation. Given the challenges faced by the Palestinian labor force and the potential harm caused by precarious work, it is critical to understand the linkages between employment instability, health outcomes, and gender and intersectional inequalities. Additionally, investigating the impact of health emergencies, like COVID-19, on this group is crucial. This study aims to explore the effects of precarious employment and job insecurity on the health of Palestinian workers, with a focus on gender and intersectionality. The study will also examine the effects of COVID-19 on the economic and health outcomes of these workers. Mixed methods approach will be utilized building on secondary data analysis, a national survey, and a qualitative exploratory study. Community involvement and capacity building will be key components of this project, including the formation of an advisory committee of stakeholders, training activities, exchange visits with collaborators, and ongoing mentorship.",,2029,Birzeit University,707970.66,Human Populations,Other,Adults (18 and older),Unspecified,Internally Displaced and Migrants | Women | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Eastern Mediterranean,Unspecified,,,,Palestine,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2024 +P30001,227788/Z/23/Z,Understanding Zika virus-induced neuropathogenesis and neurotropism,"Zika virus (ZIKV) evolved from an overlooked mosquito-borne flavivirus into a global health threat. However, the molecular mechanisms underlying this new ZIKV neuropathogenicity (e.g., microcephaly) are not understood. I hypothesise differences in tropism and inflammatory host responses, between African and American ZIKV lineages, underlie different pathologies in the developing brain. In a comprehensive approach, I will compare viral replication, viral gene expression, and host responses in a series of tractable models selected to reproduce the in vivo development of the human brain, including cerebral organoids. I will combine RNA sequencing and ribosome profiling methods established in my laboratory to measure virus and host responses, directly comparing African and American isolates. I will then test mechanistic hypotheses formed by manipulating host gene (RNAi/CRISPR-Cas9) or viral gene (reverse genetics mutants) expression and examining effects on virus replication and host response. This will also include the characterisation of the novel virulence factors I recently discovered to differ between African and American ZIKV. In this way, I will gain the most complete understanding of ZIKV inflammation mechanisms and pathogenesis drivers, and the functional viral genetics distinguishing African and American strains, to inform novel therapeutics and public health measures.",,2032,University of Cambridge,3309519.45,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease pathogenesis",2024 +P30002,223271/Z/21/A,Viral Variant Conversations - Improving the understanding of SARS-CoV-2 variants in Malawi,"The introduction of SARS-CoV-2 sequencing to new settings during the COVID-19 pandemic can be hampered by a lack of understanding of the value of genomic surveillance and concerns which may be amplified by alarmist media messaging. Clear public engagement to accompany SARS-CoV-2 sequencing training is beneficial to ensure maximum public health benefit. We will use the combined sequencing and communications expertise of COG-Train (University of Cambridge) with the public engagement, radio and co-production experience of the Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) to improve public and community engagement in Malawi. We will deliver in-person and online training courses in the communication of SARS-CoV-2 variant information to scientists and public health officials in Malawi. The courses will be devised by communications specialists at the Malawi University of Business Studies using COG-Train material and include collaborative consultations via established radio listening clubs. A series of eight radio programmes will be aired and feedback collected from audiences. The training material and broadcasts will be repackaged to create online resources suitable for sharing with the Wellcome Africa and Asia Partnership (AAP) countries. We hope that the proposal will contribute to an open environment where trustworthy genomics research can benefit all of society.",,2023,University of Cambridge,59775.93,Human Populations,Black,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Community engagement | Communication,2022 +P30006,223610/B/21/Z,Establishing genomic epidemiology hubs across Latin America,"In 2020 The Pan American Health Organization (PAHO) established and now coordinates the COVID-19 Genomic Surveillance Regional Network. It includes 21 collaborating countries of which 10 do not have any appropriate in-country sequencing capacity and instead send their samples externally for sequencing to the network reference laboratories in Brazil and Chile. Here we propose to build direct sequencing and analytical capacity in all participating laboratories to generate relevant genomic data that can be used for public health decision making. Where batch sequencing capacity already exists we propose to use MinIon platforms to extend the within-country capacity to investigate changing patterns of disease. Combined, this will dramatically increase our understanding of the known and new SARS-CoV-2 variants circulating in this region. We will develop a hub-and-spoke organization with PAHO at the center forming the hub for coordination, training and data flow and the Network laboratories forming the spokes. Laboratories with existing genomics expertise will help build genomics surveillance capacity in those that don't. Combining local and international expertise we aim to develop a regional network able to produce actionable SARS-CoV-2 data now with the potential to become a sustainable network able to track other diseases of regional importance in the future.",,2024,"World Health Organization, Switzerland",,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Switzerland,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations",2021 +P30007,227570/Z/23/Z,Investigation of interactions between the SARS-CoV-2 RNA polymerase and host cells,"SARS-CoV-2 is a novel human pathogen that emerged in late 2019 and caused a global pandemic. Despite the implementation of vaccinations and drugs to control the disease, SARS-CoV-2 continues to evolve and adapt to antiviral measures. Therefore, new approaches are needed to control the viral infection. The viral RNA polymerase complex is a conserved enzyme responsible for viral genome transcription and replication, making it an attractive target for drug development. The replication of the viral genome requires several cellular processes, and it is crucial to identify the host factors that directly participate in viral replication and to characterise their roles in regulating viral polymerase functions. My research will build upon previous studies on virus-host interactions and use state-of-the-art techniques to further analyse polymerase-host interactions. This project aims to gain mechanistic insight into SARS-CoV-2 genome replication, transcription and cellular machinery involved in viral replication. By gaining insights into the molecular and cellular biology of SARS-CoV-2, we hope to improve our understanding of host adaptation of SARS-CoV-2 and improve the antiviral preventive and therapeutic approaches. Keywords: SARS-CoV-2, viral RNA polymerase, replication, transcription, virus-host interactions",,2028,University of Oxford,658816.7,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2024 +P30009,223610/A/21/Z,Establishing genomic epidemiology hubs across Latin America,"In 2020 The Pan American Health Organization (PAHO) established and now coordinates the COVID-19 Genomic Surveillance Regional Network. It includes 21 collaborating countries of which 10 do not have any appropriate in-country sequencing capacity and instead send their samples externally for sequencing to the network reference laboratories in Brazil and Chile. Here we propose to build direct sequencing and analytical capacity in all participating laboratories to generate relevant genomic data that can be used for public health decision making. Where batch sequencing capacity already exists we propose to use MinIon platforms to extend the within-country capacity to investigate changing patterns of disease. Combined, this will dramatically increase our understanding of the known and new SARS-CoV-2 variants circulating in this region. We will develop a hub-and-spoke organization with PAHO at the center forming the hub for coordination, training and data flow and the Network laboratories forming the spokes. Laboratories with existing genomics expertise will help build genomics surveillance capacity in those that don't. Combining local and international expertise we aim to develop a regional network able to produce actionable SARS-CoV-2 data now with the potential to become a sustainable network able to track other diseases of regional importance in the future.",,2024,Wellcome Sanger Institute,130762.73,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics,2022 +P30010,226392/Z/22/Z,"Community mental health treatment and subsequent outcomes in children and young people: what works, for whom, and why?","The sequelae of children and young people's (hereafter: CYP) mental disorders are broad and long-lasting.1,2 Despite pledges to increase mental health funding in the UK,3 CYP experience difficulties accessing services and long wait times.4 Since the start of the COVID-19 pandemic, population studies suggest that CYP's mental health deteriorated,5-8 with a 53% increase in contacts made to CYP's mental health services (MHS) in England compared to before the pandemic.9 Given rising demands, it is crucial that MHS for CYP are optimised. There is a paucity of information regarding effectiveness of treatment-as-usual MHS in CYP, with uncertainties regarding which individuals improve, and whether similar outcomes would be seen without treatment.10 This proposal aims to: - assess the effectiveness of community MHS on CYP's mental health and functioning compared with those who do not to access treatment; - better understand which MHS contacts are helpful for whom (moderation) and why (mediation); - determine whether prior contact with MHS protect CYP against pandemic-related impairments and under what circumstances. Findings will inform clinicians and policy makers of how to optimise the effectiveness of MHS, and to improve commissioning and delivery to better meet the needs of CYP.",,2028,University of Cambridge,698190.15,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P30011,227438/Z/23/Z,Harnessing epidemiological and genomic data for understanding of respiratory virus transmission at multiple scales,"Modern large-scale genetic and epidemiological data offers a potential revolution in our understanding of the transmission of viral respiratory pathogens particularly if appropriate methods can be developed and applied to combine information sources and extract the necessary scientific insights. The requirement for such a revolution was illustrated by the ubiquity of more traditional analyses to inform our response to the COVID-19 pandemic. Delivering advances in understanding of respiratory pathogens would in turn drive major improvements in the public health policies designed to mitigate the heavy burden respiratory infections placed on individuals and health and social care services. The epidemiology of such pathogens is driven by a largely unobserved process of community infection, and we propose to make particular use of the ONS COVID-19 Infection Survey (CIS), a very large (500,000 participant) longitudinal (2-year) household cohort study, which has now passed 10 million visits. We propose a set of interlinked analyses of CIS and other datasets, developing advanced genomic, data science and modelling methodology, to disentangle routes of transmission, to understand relationship between the community and other settings, and ultimately to inform policy on control of respiratory viruses.",,2027,University of Manchester,1326427.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics,2024 +P30012,219763/Z/19/Z,Effectiveness of vaccines to prevent antibiotic prescribing for acute respiratory tract infections in high risk adults,"In high income countries the greatest use of antibiotics is in community (primary care) settings in the context of acute respiratory tract infections. Within these settings, both the very young, the very old and those with respiratory conditions such as asthma and chronic obstructive pulmonary disease are known to be the greatest antibiotic users. While there are a number of vaccines routinely provided that protect against acute respiratory tract infections, there is limited empirical data quantifying the potential benefit of vaccines to reduce antibiotic use for respiratory tract infections, particularly in adult populations. In this project we will use a large-scale database of electronic general practice records to quantify, in older adults, the effectiveness of influenza, pertussis and pneumococcal vaccines in reducing primary care presentations for acute respiratory tract infections and subsequent antibiotic prescribing. We will focus on high risk groups defined by age and/or co-morbidity (asthma and chronic obstructive pulmonary disease). We will use these estimates of vaccine effectiveness to model the absolute reductions in antibiotic use that could be obtained by increasing vaccine coverage in different adult sub-groups. This evidence will enable policymakers to better prioritise strategies to increase uptake of these vaccines.",,2023,University of New South Wales,243077.1,Human Populations,Unspecified,Older adults (65 and older),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Western Pacific,Unspecified,,,,Australia,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2021 +P30013,226630/Z/22/Z,"4M: Microbes, Milk, Mental Health and Me; how do early life gut microbiota and feeding shape long-term mental health in the C-GULL Cohort?","The global burden of mental health conditions is a profound public health challenge, worsened by the COVID-19 pandemic, and yet we know little about their early-life origins. Compelling evidence points towards microbial gut colonisation, strongly influenced by breastmilk, as an important determinant of neurodevelopment trajectories and mental well-being via the microbiota-gut- brain axis, but there is little definitive research on the mechanisms. To help close this knowledge gap, we propose '4M: Microbes, Milk, Mental Health and Me' - enhancing the Children Growing up in Liverpool (C-GULL) programme by enabling collection of additional bio-samples, state-of-the-art gut microbiota and breastmilk profiling, and rigorous mechanistic exploration of the causal pathways underlying adverse mental health outcomes in this richly-phenotyped birth cohort. We will generate, integrate, and interrogate large-scale genomic and epidemiological datasets to perform experimental testing, biological discovery, causally robust epidemiology, and translational science. We will also create an internationally unique archive of paired bio-samples from mothers and babies and identify keystone bacteria and milk constituents that influence neurodevelopment and mental health. This will generate robust evidence for preventative and therapeutic interventions (e.g., diet, Live Bacterial Therapeutics) to restore and select for age-appropriate beneficial species to optimise a child's resistance to adverse mental health conditions.",,2029,University of Liverpool,8179802.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2024 +P30014,227041/Z/23/Z,Predicting the future for avian Influenza using a One Health immuno- epidemiological framework,"The pandemic potential of avian influenza considering life-long influenza infection histories, both in animal and human populations, is an unresolved question. The age distributions of influenza cases in pandemics and avian influenza spillover events suggest prior infection as an important factor. In this fellowship, I will develop an immuno-epidemiological framework to understand the interplay between life-histories of influenza infection in birds, humans and at the animal-human interface to predict pandemic conditions. Using transmission models for wild birds and humans I will investigate the hypothesis that subtype-specific infection in early life influences future susceptibility and disease dynamics of influenza A. High- throughput multiplex immunoglobulin and surrogate neutralisation assays will be developed and deployed to longitudinal birth cohorts of humans and wild birds of long-life spans. Serological profiles will be used to reconstruct subtype-specific infection histories. From this, I will calculate the frequency of influenza infections in the host population and evaluate cross- reactivity. Sero-epidemiological findings will be integrated back into mathematical models to determine conditions for pandemic potential. This work will deepen our understanding of the influenza immunity landscape for zoonotic disease control and pandemic prediction.",,2028,University of Bristol,883310.91,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Animal and environmental research and research on diseases vectors",Immunity | Disease transmission dynamics | Disease surveillance & mapping | Animal source and routes of transmission,2023 +P30015,226721/Z/22/Z,Synthetic reduced-vector-competence traits in Aedes aegypti,"Vector-borne diseases, mostly mosquito-borne, account for >17% of all infectious diseases of humans. Disease caused by ARthropod-BOrne viruses (arboviruses, e.g. dengue, chikungunya and Zika viruses) continue to escalate, the burden falling overwhelmingly on Low-and-Middle-Income Countries (LMICs) and likely exacerbated by climate change affecting mosquito distribution. These 'neglected tropical diseases' impact development, e.g. Millennium Development Goals, as well as their direct human burden. Arboviruses are also among the key emerging infectious diseases/priority diseases of epidemic potential. New cost-effective, sustainable, environmentally-friendly methods for controlling arboviruses are sorely needed. Here we propose to develop broad-spectrum anti-viral traits in engineered mosquitoes. By ""broad-spectrum"" we mean active against multiple arboviruses, in contrast to the current state of the art for synthetic anti-viral (""reduced vector competence"") traits, RNAi-based systems which provide resistance only against specific viruses or virus strains. This is important for vectors such as Aedes aegypti, which can transmit a range of important viral pathogens. Such tools could be delivered to wild vector populations via mating between released modified mosquitoes and wild mosquitoes. These methods are egalitarian - everyone within the protected area is equally protected, irrespective of wealth, ethnicity, gender, education etc.",,2028,University of York,3828021.62,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Animal and environmental research and research on diseases vectors,Vector control strategies,2023 +P30016,221963/Z/20/Z,Socio-ecological dynamics of zoonotic and vector-borne diseases in changing landscapes: implications for surveillance and control,"Landscape changes disrupt infectious disease dynamics, requiring new approaches to characterise risks and prevent outbreaks. Focusing on emerging (Chikungunya, Zika) and epidemic (malaria, dengue) zoonotic and vector-borne diseases in Malaysia and the Philippines, I aim to design and evaluate enhanced surveillance systems linking health and environmental data to detect and prevent pathogen spillover and transmission. By developing novel models relating social and ecological processes across spatial and temporal scales, I will bridge critical gaps linking environmental change with human behaviour and health systems. Fine-scale studies of human mobility, behaviour and infection risks will be integrated within a large-scale experiment on tropical forest modification to understand how landscape change both interacts with and alters environmental factors (e.g. seasonality, biodiversity) and socioeconomic and biological factors (e.g. demography, mobility, immunity) to determine disease dynamics. Statistical and mathematical models will be used to explore factors across ecological settings, integrating routine surveillance data, population-based serological surveys and multitemporal Earth Observation data to reconstruct historical disease transmission over major environmental shifts. Predictive models will be designed to identify how future land use can reduce disease risks and how control programmes can use environmental data from new sources of real-time Earth Observation data to improve disease surveillance.",,2026,University of Glasgow,1636310.9,Human Populations | Disease Vectors | Viruses | Environment,Not applicable,Not Applicable,Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Unspecified,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies",Environmental stability of pathogen | Animal source and routes of transmission | Vector control strategies | Disease surveillance & mapping,2021 +P30017,224530/A/21/Z,"Genomic and transcriptomic determinants of host susceptibility, protection, and viral mutation in experimental SARS CoV-2 infection","This project aims to use samples collected during the world's first SARS-CoV-2 human challenge studies to investigate in depth how pre-existing immunity and virus-host interactions affect the outcome of infection. Two SARS-CoV-2 human challenge studies are currently underway that together are enrolling naïve, previously infected and vaccinated young adults for controlled infection with a well-characterised viral inoculum. This proposal will investigate the genomic and cell-specific variations in host response that may be responsible for differential clinical outcome and within-host viral variation. Since in- host mutation is the mechanism by which viruses escape vaccine-mediated protection, further understanding of its drivers is an urgent priority to help anticipate the emergence of vaccine-resistant variants. Single-cell RNAseq will be used to analyse the transcriptional patterns of blood and nasal cells over the course of infection. These will be correlated with the transcriptional responses of the virus in concurrent nasal samples and whole genome sequencing to identify stable mutants that arise. Incorporating each participant's genomic sequence, integrative analysis of virus and host factors that correlate with susceptibility and protection from infection and disease will be achieved. Thus, we will maximise the value of the human challenge programme and identify specific targets for vaccine improvement.",,2024,Wellcome Sanger Institute,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P30018,226141/A/22/Z,G2P - Global Knowledge Exchange to Enable In Country Risk Assessment of SARS CoV-2 Variants,"SARS CoV-2 continues to evolve. Novel variants are driven by high levels of global transmission and viral replication, sustained selection pressures imparted by existing immunity acquired through natural infection and vaccination, and increasing use of antivirals. Building on G2P-UK, established working partnerships between teams in the UK, Africa and India, and an ethos of free knowledge exchange, we outline 4 inter-related aims that will enable and prepare G2P-Global to evaluate the significance of emerging viral variation across 3 continents. We will: 1) Implement standardized methodologies that enable rapid in-country risk assessment of the biological and antigenic properties of SARS-CoV-2 variants of concern (VOCs), providing real-time data for guiding infection control and vaccination policies; 2) Undertake discovery-led molecular, cellular and in vivo (hamster) analyses of variant phenotypes to address the mechanistic basis for how the virus can evolve while balancing immune escape with the maintenance of efficient respiratory transmission; 3) Assess the potential for spill-overs into domesticated and wild animal species and subsequent reservoir seeding; 4) Establish communications networks and laboratory resources that will build technical and logistical preparedness enabling G2P-Global partners and additional collaborators to undertake in-country virological assessments of future respiratory virus outbreaks, and associated virus variants.",,2026,"National Centre for Biological Sciences, India",,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,Unspecified,,,,India,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities",2023 +P30019,222903/Z/21/Z,High throughput genomic sequencing to understand the transmission and biology of human pathogens,"Pathogen genetic sequencing is benefiting from improved laboratory workflows. COG-UK and the CARRIAGE study facilitate nation-wide acquisition and processing of SARS-CoV-2 and Staphylococcus aureus genomic data. I will utilise genomic and individual-level epidemiological data to understand the transmission and carriage dynamics. SARS-CoV-2 and Staphylococcus aureus are major human pathogens with significant disease burden. Importations of SARS- CoV-2 into the UK and transmission within University settings are considered sources of sustained SARS-CoV-2 spread and subject to restrictive measures, though poorly understood. S. aureus is an established pathogen in human populations and results in persistent nasal colonisation of approximately 25% of healthy people. Understanding the factors that result in transmission and colonisation of both pathogens, respectively, is vital to reduce subsequent disease. I will: 1) Characterise the contribution of imported SARS-CoV-2 to onwards transmission by coupling travel histories derived from Test and Trace to genetically linked clusters of infection. 2) Identify the transmission dynamics of SARS-CoV-2 by sequencing isolates derived through the University of Cambridge screening programme. 3) Characterise the microbial community structure that facilitates nasal Staphylococcus aureus carriage through microbiome analysis of 10,000 CARRIAGE study participants. 4) Experimentally validate genomic findings from microbiome data to identify pathways that facilitate S. aureus carriage",,2024,University of Cambridge,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P30021,219759/Z/19/Z,Vaccine-avertable antimicrobial prescribing from influenza and RSV: a mixed- methods observational study,"Vaccines against viruses can reduce antibiotic prescribing by reducing the incidence of viral infections that are inappropriately treated with antibiotics, as well as by reducing the incidence of secondary bacterial infections caused by viral infections. We will estimate the magnitude of this effect for influenza vaccination and the potential magnitude for Respiratory Syncitial Virus (RSV) vaccination and enhanced influenza vaccination. First, we willestimate the antimicrobial prescribing attributable to RSV and influenza in the Kaiser Permanente population in Northern California, USA, in total and by drug class and age group. Next, we will estimate the antimicrobial prescribing currently averted by influenza vaccination by comparing antimicrobial prescribing in (1) persons who have not received influenza vaccine vs. (2) persons who have, controlling for age and location within northern California, in aggregate and stratified by age and antimicrobial class. Using these results, we will estimate the number and proportion of antimicrobial prescriptions that may potentially be averted by improved influenza vaccines and (separately) by RSV vaccines that are now investigational, assuming various possible levels of coverage and effectiveness. Notable features of our analysis will be extensive measures to avoid confounding and an examination of waning of influenza prescribing effects with time since vaccination.",,2023,Harvard University,533833.69,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,"Vaccines research, development and implementation",,2020 +P30023,224845/Z/21/Z,'COVID-19 Genomics - MENA': towards molecular surveillance of SARS-CoV-2 genomes during the vaccination period within the Middle East and North Africa,"We propose to form a consortium of researchers representing the MENA region ('COVID-19 Genomics MENA') with access to COVID-19 samples for setting up sequencing and analytical pipelines for large-scale sequencing-based genomic surveillance of the circulating lineages of the SARS-CoV-2 virus. The consortium will consist of investigators from four countries in the Middle East (Saudi Arabia, Qatar, Oman, and Kuwait) and three countries (Algeria, Morocco, and Egypt) in North Africa. The aim of this proposal is to sequence a large number of SARS-CoV-2 genomes for molecular tracking of the circulating lineages of the virus during the active vaccination period for the next 12 months. We pledge to sequence 12,000+ SARS-CoV-2 genomes and collect relevant clinical meta-datasets during the next 12 months in these seven countries in the MENA region. We shall be using a combination of next-generation sequencing technology platforms (Illumina, Oxford Nanopore, and Ion Torrent) and standard genome assembly, genomic-epidemiology analytical pipelines already available within the laboratories in the consortium. The resulting datasets will be made publicly available through the GISAID data portal for wider accessibility of the datasets. We also aim to integrate a 'training component' for local capacity building at the participating institutions in the MENA region.",,2024,King Abdullah University of Science and Technology,1900449.64,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Eastern Mediterranean,Unspecified,,,,Saudi Arabia,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P30024,227520/Z/23/Z,"Uncovering endemic Rift Valley fever patterns at the human-animal- environmental interface to model transmission in Kajiado County, Kenya","Rift Valley fever virus (RVFV) is a zoonotic virus transmitted by mosquitos. As cattle, sheep, and goats increase local viral activity, humans can also be exposed by contacting infected livestock fluids. If livestock infections are controlled, public health risks are reduced, but in all species, RVFV is hard to differentiate from other diseases without targeted sampling and testing. Cases are increasingly detected between large outbreaks, but the extent is unknown because current testing systems are not designed to capture them. This perpetuates a biased understanding of epidemiology. With potential for severe human disease, economic impact on livestock, and no human vaccine option, current understanding of how RVFV moves through populations in hotspots does not reflect the global importance of the disease. This study aims to uncover local outbreaks in humans and animals to understand the extent of endemic transmission and risk. We will also collect livestock movement and vector data to use in adapting a simulation model made for another livestock disease to determine what factors are important for RVFV spread. Finally, since human behaviors impact risk and control of disease, we will integrate a qualitative study that summarizes the community's perspective of barriers and facilitators to controlling livestock diseases.",,2025,University of Liverpool,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease transmission dynamics,2022 +P30025,223011/Z/21/Z,Microenvironment Regulation of Zika Virus Susceptibility in Human Brain Development and Malignant Glioma,"Neural stem cells (NSCs) in the developing embryo brain share transcription programs with glioma stem cells (GSCs) in malignant brain tumours, and both are susceptible to Zika Virus infection. In the developing brain this can result in microcephaly, whereas in brain tumours it could offer insights relevant to oncolytic virus development. However GSC and NSC susceptibility to Zika and other viruses depends on the microenvironment. In particular, microglia progenitors migrating into the embryo brain from the yolk sac are believed to bring virus with them, whereas my preliminary data suggests that mature tumour-associated microglia instead drive a virus resistance phenotype in GSCs. This project seeks to establish the mechanistic basis for the microenvironment regulation of virus susceptibility in normal and malignant progenitors, and to suggest therapeutic strategies for modulation of these.",,2027,University of Cambridge,1065619.32,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Unspecified,,,,,,,,,Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history",2023 +P30027,225459/Z/22/Z,Science-to-Policy; A Global Media Network Bridging North-South Divides,"Wellcome's strategic focus on four themes: infectious disease; climate; mental health; and discovery research covers many of the gravest challenges facing low- and middle-income countries. Translating new knowledge into policy, however, remains challenging. There remains little investment, particularly in LMICs, in independent global health media to air discoveries, channel debates, and hold policymakers accountable. Health Policy Watch provides a platform for LMIC journalists to develop and share their stories, echoing in both global North and South, and building capacity of LMIC media professionals. A 2020-21 Wellcome Grant led to a two-fold increase in Health Policy Watch readership, including in major LMIC 'hubs', e.g. South Africa, Kenya, Nigeria, India, Pakistan. This proposal aims at solidifying gains in a sustainable model focused on: 1. Reporting from Africa and Southeast Asia around Wellcome priorities - a) Tracking countries' action on health-relevant aspects of climate commitments and health co-benefits of sustainability in under-explored themes. b) LMIC challenges battling infectious diseases, including SARS-CoV2 in an equity & health systems lens; c) preventing new pandemics in a One- Health framework; d) African & Asian discovery research. 2. Sustainable media model - recruitment of other major donors; microfinance through targeted social media appeals, media collaborations and advertising.",,2025,Global Policy Reporting,258364.83,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Other,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Communication,2022 +P30029,225001/Z/22/Z,Developing the next generation of epidemiological analytics using individual- level virologic and serologic data,"SARS-CoV-2 has revealed serious inadequacies in how we track infectious disease spread. Despite progress in quantifying individual-level biomarkers at scale, inferring transmission dynamics to inform public health decisions still largely depends on counting cases. Recently, I showed that individual-level viral load measurements from a single cross-sectional sample of RT-qPCR data can accurately estimate an epidemic's trajectory, overcoming many limitations of case count-based surveillance. Here, I will build a new generation of outbreak analytic tools, leveraging individual-level immunological and pathogen titres to robustly estimate transmission dynamics. First, I will integrate virologic and serologic data from the UK's SARS-CoV-2 surveillance studies to create a new modelling framework coupling within-host viral and antibody kinetics with population-level dynamics. Using this framework, I will evaluate prioritization of different surveillance strategies across pandemic phases. Second, I will develop new epidemiological inference methods harnessing biological kinetics, validated using UK SARS-CoV-2 data, and evaluated for use in resource-limited settings. Finally, I will integrate viral load data with phylodynamics to improve the rapid characterization of emerging viral variants. Overall, this research will advance how we use individual-based information for infectious disease surveillance, establishing the study of viral load dynamics, or viroepidemiology, as a key tool alongside seroepidemiology and phylodynamics.",,2027,University of Oxford,540373.7,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease surveillance & mapping,2022 +P30030,226130/Z/22/Z,Platform for rapid immunological characterization of SARS CoV-2 variants in Kenya and the Eastern Africa Region,"We propose to augment our well-established genomics surveillance infrastructure with a well-structured and coordinated platform for continuous immunological surveillance and characterization of emerging SARS-CoV-2 variants within Kenya and the Eastern Africa region. We will assemble a network of collaborating health facilities across Kenya and the Eastern Africa region to contribute genomic and immunology samples. Our current status as an Africa CDC/WHO-AFRO regional genomic reference laboratory has facilitated bidirectional sample and data sharing with Ministry of Health teams from Eastern Africa and will be a key feature of the immunology work. We will determine whether newly emergent variants exhibit substantial changes in their sensitivity to neutralization by antibodies induced by vaccination and natural infection, and consequently predict the likely impact on vaccine effectiveness. In addition, we will establish a monoclonal antibody discovery pipeline to rapidly identify variant specific or cross-neutralizing monoclonal antibodies. The network will therefore produce directly actionable health intelligence to support local and international public health policy adjustments to curtail the negative health and economic impacts of the virus.",,2026,Kemri-Wellcome Trust Research Programme,2727834.39,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,Data Management and Data Sharing,,,Kenya,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2023 +P30031,224494/Z/21/Z,Long-term consequences of Zika virus infections during pregnancy for school- aged children and their families in Brazil,"Using unparalleled epidemiological, administrative, and social science data continuously collected from 2015 onwards in Brazil, this collaborative proposal aims to define the prognosis and learning needs of school-aged children with prenatal exposure to Zika virus (ZIKV) and the long-term health and social impacts for families of children with Congenital Zika Syndrome (CZS). Through four linked work packages, we will: (i) define the natural history of CZS in the first 12 years of life, including the frequency of late- onset manifestations, hospitalizations, and deaths, (ii) compare neurodevelopment and learning-related outcomes in children with and without CZS, (iii) evaluate long-term consequences of CZS for families, including implications of COVID-19, and (iv) critically interrogate the experience of families engaging in research and data sharing initiatives during and after public health emergencies. To achieve these aims, we are requesting resources to perform comprehensive clinical and neurodevelopmental assessments in the Microcephaly Epidemic Research Group and ZIKAIFF Pediatric Cohorts in Pernambuco and Rio de Janeiro states, undertake a nationwide individual participant data meta-analysis of ZIKV-related clinical and neurodevelopmental outcomes among children in the Zika Brazilian Cohorts Consortium, link large- scale nationwide electronic health and social records in the CIDACS/Fiocruz Zika Platform, and conduct qualitative research with key stakeholders.",,2029,London School of Hygiene & Tropical Medicine,826834.53,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Policy research and interventions | Indirect health impacts,2022 +P30032,222574/Z/21/A,Policy and public engagement to promote the understanding and use of genomic data during decision making,"During the COVID-19 pandemic, genomic sequencing has provided valuable information on the spread of SARS-CoV-2 to ensure timely and targeted public health responses. Genomic surveillance programmes have been set up within Wellcome's Africa/Asia Programmes (AAPs) and CIDRI in South Africa. However, there is suboptimal national-level resource allocation, insufficient strategy for sampling of specimens to optimize epidemiological and clinical inference, and gaps in meta-data needed to fully and quickly interpret genomic sequencing information. Policy makers presented with genomic data to support decision making must decide if a response is needed, how large the response should be, for whom, and when. To do this, a systematic approach to assessing genomic evidence is needed. It is also unclear what the public knows about SARS-COV-2 genomic sequencing, even though some media reports and anecdotal data from current policy and public engagement work being undertaken in the AAPs may suggest limited understanding of SARS-CoV-2 variants among this audience. Through a suite of engagement activities at the AAPs, we will target both the public and policy makers to 1) increase the public's understanding of SARS- COV-2 genomic sequencing, and 2) support national level strategies by developing tools that guides the assessment of genomic evidence.",,2024,University of Oxford,227494.46,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Communication,2022 +P30033,224055/Z/21/Z,Understanding the long-term haematological consequences of infection exposure,"Infectious disease remains a global health burden. Blood and immune cells play a central role in underlying pathology, however long-term consequences of infection on these cells in otherwise healthy people are unknown. This project aims to understand whether infection modifies cellular programmes, leaving scars on the haematopoietic system, even after recovery, that compromise health in later life. Using a murine influenza model, non-infected, infected and recovered groups (where subjects are administered antiviral treatment post-infection and are analysed after a period of time) will be investigated. By combining a DNA barcoding tool with single cell Multiome analysis of bone marrow cells from these groups, a high dimensional comparison of the transcriptome and epigenome of sister cells will be generated. These data will address fundamental questions including whether cell fate potential is and remains perturbed by infection. Next, following bioinformatic stratification of the data and employing in vitro functional experiments to screen candidate genes using CRISPR-Cas9, molecular targets to be manipulated in vivo will be identified. These experiments will address whether it is possible to mitigate effects of infectious perturbations on the haematopoietic system. Overall, this work will begin to elucidate mechanisms driving the response to infection and highlight potential therapeutic interventions.",,2027,University of Cambridge,368022.5,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2023 +P30035,220776/Z/20/Z,Mechanism of cell-to-cell transmission of flaviviruses,"This proposal will investigate the mechanism of cell-to-cell transmission and spread of flaviviruses using Dengue and Zika as model systems. We will therefore address a longstanding debate on how they exit from infected cells, and preferentially spread into specific cell types. Dengue and Zika are the two most prevalent flaviviruses worldwide, sharing significant overlap in their genome architecture and biology. Dengue infects >50 million people annually, causing severe pathologies. Zika too has emerged as a global threat with recent outbreaks linked to serious neuro-developmental complications in children and Guillain Barré syndrome in adults. No vaccines or therapeutics exist for these viruses, and our current understanding on mechanisms of their transmission and spread is severely limited. Viral infections spread by overcoming multiple barriers to move from cell to cell. Viral progenies can move across extracellular space either as free particles via fluid phase diffusion, within vesicles, or by cell-cell contacts. To understand transmission, we will therefore address: (i) characteristics of the extracellular virus populations, (ii) whether multiple transmission routes exist (iii) whether the viral envelope is the primary determinant of transmissibility. This proposal builds on our previously published and ongoing studies on viral manipulation of autophagy for assembly and spread.",,2025,University of Oxford,2118600.63,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P30036,224530/Z/21/Z,"Genomic and transcriptomic determinants of host susceptibility, protection, and viral mutation in experimental SARS CoV-2 infection","This project aims to use samples collected during the world's first SARS-CoV-2 human challenge studies to investigate in depth how pre-existing immunity and virus-host interactions affect the outcome of infection. Two SARS-CoV-2 human challenge studies are currently underway that together are enrolling naïve, previously infected and vaccinated young adults for controlled infection with a well-characterised viral inoculum. This proposal will investigate the genomic and cell-specific variations in host response that may be responsible for differential clinical outcome and within-host viral variation. Since in- host mutation is the mechanism by which viruses escape vaccine-mediated protection, further understanding of its drivers is an urgent priority to help anticipate the emergence of vaccine-resistant variants. Single-cell RNAseq will be used to analyse the transcriptional patterns of blood and nasal cells over the course of infection. These will be correlated with the transcriptional responses of the virus in concurrent nasal samples and whole genome sequencing to identify stable mutants that arise. Incorporating each participant's genomic sequence, integrative analysis of virus and host factors that correlate with susceptibility and protection from infection and disease will be achieved. Thus, we will maximise the value of the human challenge programme and identify specific targets for vaccine improvement.",,2024,Imperial College London,2363066.9,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Immunity | Disease models | Prognostic factors for disease severity | Disease pathogenesis",2022 +P30037,224459/Z/21/Z,Transitioning the WMP Wolbachia method for arbovirus control to sustainable scale,"Approximately 40% of the global human population is at risk of acquiring a virus transmitted by the bite of an Aedes aegypti mosquito this year. These viruses cause diseases known as dengue, Zika, chikungunya and yellow fever. Infection can result in death, but in less extreme manifestations it can result in horrific birth abnormalities in babies, extended periods of illness and hospitalisation, loss of income through an inability to work, and disruption of the health system through inundation with people seeking urgent care during outbreaks. Sadly, there are no effective and safe drugs or vaccines available, nor effective methods for controlling the mosquito. As a result the disease burden is climbing year on year. We have found that introducing a natural insect bacterium (Wolbachia) into wild mosquito populations can eliminate the ability of mosquitoes to transmit all of these viruses between people. We have shown this method to be highly efficacious and has the potential to lead to disease elimination. Our goal now is to optimise the remaining technical areas that constrain scaling and to help to build the capacity and undertake the knowledge transfer that will make the intervention available to the billions of people that need it.",,2026,Monash University,19859546.86,Disease Vectors,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Other,,,,,,,,,Zika virus disease | Congenital Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Western Pacific,Unspecified,,,,Australia,,Animal and environmental research and research on diseases vectors,Vector control strategies,2021 +P30038,226088/Z/22/Z,Mosqlimate,"For 40 years, Brazil has witnessed the emergence of diseases transmitted by the mosquito Aedes aegypti: DENV-1 (1986), DENV-2 (1991), DENV-3 (2001), DENV-4 (2010), Chikungunya (2014), and Zika (2015), with severe human and economic costs. Viruses at risk of introduction are Nhong-nhong, Mayaro, and Oropouche. Misdiagnosis is common, and emergence of new viruses can go largely unnoticed. New tools are needed to increase the precision of arbovirus surveillance and control in preparation for climate change. Mosqlimate is a multi-disease tool with two main goals: 1) estimate probabilities of change in pattern of disease transmission in response to climate and land use changes; 2) identify circulating viruses during outbreaks when information is incomplete. Mosqlimate will detect signs of expansion of arbovirus transmission areas, as well as signs of outbreaks potentially linked to new arboviruses. The tool will flexibly feed on climate and epidemiological data whenever available. Another tool, OviCounter, will fill in the mosquito data gap by providing digital technology to improve the use of eggtraps for mosquito surveillance at large scale. As output, Mosqlimate will deliver measures of risk to integrate into the Brazilian early warning system ""Infodengue"" and its mature community of practice.",,2027,Fundação Getulio Vargas,624411.32,Disease Vectors | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae | Flaviviridae | Other,,,,,,,,,Rift Valley Fever | Zika virus disease | Congenital Zika virus disease | Other,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,Brazil,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P30039,222037/A/20/Z,Cross Cutting Social Science Research for COVID-19,"The global community has mobilised in an unprecedented way to deliver research in response to the threat of COVID-19. In February 2020, priority areas for research were advanced under a coordinated mechanism convened by the World Health Organisation. For social science a cross cutting research agenda was proposed in recognition of the vital role played by individuals, communities and populations worldwide in slowing disease tranmssison and providing care for COVID-19 and beyond. Research initiatives, including over 300 social science studies funded by GloPID-R members alone, have been advanced against these social science priorities. Building on earlier successes in supporting epidemic-relevant research, the research arm of GOARN, the Global Outbreak Alert and Response Network, has actively coordinated this work with WHO. There is a pressing need to properly resource coordination and knowledge mobilisation of epidemic-relevant social science research. Further, there is an important opportunity to leverage the reach and expertise of GOARN and establish infrastructure for the COVID-19 response as well as for future scenarios to ensure that structures for epidemic-relevant research can take hold: the well worn phrase of ""building the ship while we sail it"" is unsustainable as an effective and efficient research response to infectious disease epidemics.",,2025,"World Health Organization, Switzerland",432009.71,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Switzerland,,"Policies for public health, disease control & community resilience",Community engagement,2020 +P30040,222889/Z/21/Z,Characterisation of immune responses to vaccination against SARS-CoV-2,"COVID-19 is an infection caused by a virus that first emerged at the end of 2019 and has since been declared a global pandemic. Multiple vaccines have been in development globally including three vaccines that have now been approved for use in the UK. At Imperial College London a novel self-amplifying RNA (saRNA) vaccine has been developed and is being used as part of a clinical trial since June 2020 (COVAC1). Those who have already had a natural SARS- CoV-2 infection are likely to have some protection against further infection, although reports of re-infection do exist. It is not clear how long such protection would last and so it is important to understand how a vaccine may boost the immune response in these individuals. In order to explore this, I plan to look at immune responses up to one year post vaccination against SARS- CoV-2 using both the Imperial saRNA vaccine and the Pfizer/BioNTech mRNA vaccine in individuals who have recovered from natural infection compared to those who have never previously been infected. This will provide important information on how the immune system behaves after vaccination in those with pre-existing antibodies, and will help to inform further vaccination strategies and research.",,2024,Imperial College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2020 +P30042,226543/Z/22/Z,Pandemic Preparedness: Analytical Capacity and Funding Tracking programme (Pandemic PACT): Wellcome Funding Proposal,"The ongoing COVID-19 health emergency exposed significant problems with funding and research structures at a global level in a pandemic, resulting in an uncoordinated, fragmented and ultimately inefficient research funding response. The Pandemic Analytical Capacity and Funding Tracking Programme (Pandemic PACT) proposes to build on our work during the COVID-19 pandemic, to develop a broad prospective research funding tracking and analysis capability linked to major funding decision makers. The programme will collate global funding data for a wide range of epidemic prone diseases and broader epidemic and pandemic research preparedness activities on an ongoing basis. It will map these against research domains, research agendas and living Rapid Research Needs Appraisals*. The outputs will include an interactive database of the relevant research funding landscape mapped to domains and priority roadmaps (the tool); regular analyses of funding trends and research gaps; and a standing capability to rapidly identify research needs in the event of a novel outbreak or disease. These outputs will support evidence informed decision making and coordination by the world's major research funders and key policy stakeholders through directly feeding in to GloPID-R's response plan and regional hubs with the goal of improved efficiency and effectiveness of research responses.",,2026,University of Oxford,1062611.68,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,Data Management and Data Sharing,,,United Kingdom,,,,2023 +P30043,226131/Z/22/Z,Can cross-protective airway-resident immunity be harnessed for SARS-CoV-2 variant protection in UK and Malawian populations with or without HIV infection?,"Coinciding with >70% seroprevalence in Malawi and >75% vaccination coverage in the UK, the omicron variant has had lower mortality than the delta variant. Both prior infection and vaccination protect against severe COVID-19, and vaccination combined with infection induces highly cross-reactive hybrid immunity. Pre-existing cross-reactive T cells targeting highly conserved replication proteins abort SARS-CoV-2 infection before PCR positivity or antibody seroconversion, leading to protection against COVID-19. Our unpublished data suggest that this rapid immune-surveillance is attributable to pre-existing cross-reactive SARS-CoV-2 T cells that are highly enriched in the human airways. Furthermore, lung-resident B cells elicit antibodies that cross-neutralise influenza variants and recent work has highlighted the protective potential of mucosal IgA against COVID-19. These data suggest that cross-reactive airway immune responses could be critical in defence against emerging variants. We hypothesise that airway-compartmentalised T and B cells provide an enriched long-lived reservoir of cross-reactive immunity against emerging variants than can protect against COVID-19, and we postulate that is impacted by background exposure, vaccination status and pre-existing HIV infection, in Malawi and UK adults. An understanding of tissue-resident long- lived, broadly cross-reactive immunity is vital for development of next generation mucosal-targeted vaccines and for future studies predicting susceptibility to novel variants.",,2026,Liverpool School of Tropical Medicine,3322631.6,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2023 +P30045,226813/Z/22/Z,Systematic mapping and discovery of immune system's long-distance regulatory networks in severe COVID-19,"The COVID-19 pandemic, as a result of SARS-CoV-2 infection, has affected most countries with more than 6 million related deaths worldwide. Despite significant progress in understanding the pathophysiology of COVID-19 and the determinants of its severity and susceptibility, there are still gaps in understanding its wider regulatory networks. These involve both genetic and protein elements, often located significant distances away from target genes. Identification of such distal elements within those networks remains a challenge. I aim to use high-throughput CRISPR-based methods such as CRISPRi screens to characterise the large (~500kb) regions of DNA around key loci potentially involved in COVID-19 severity. I will also apply machine learning and multi-omic approaches to the existing large-scale datasets of COVID-19 patients to identify immune-related loci and disease-relevant non-coding regions, as well as integrate the experimental data generated with CRISPR screens. Characterisation of distal enhancers, promoters, and their connections on a genome scale for clinically significant loci may help to identify new pathways and therapeutic targets to alleviate the burden of infectious disease, autoimmunity and improve cancer immunotherapy.",,2025,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease pathogenesis,2022 +P30046,221350/Z/20/Z,Epidemiological modelling to support the global COVID-19 response: How to mitigate impact in low-income and crisis-affected settings,"The current COVID-19 pandemic is the greatest threat posed by a respiratory virus since 1918 H1N1 influenza pandemic. To date, the majority of epidemiological modelling analyses have focussed on High Income Countries (HICs). However, there is an equivalent need for models appropriate to Low- and Middle-Income Countries (LMICs) that comprise 85% of the world's population and have differing demographics and behaviours that are not captured by existing models. To address this, we will use a model of SARS- CoV-2 transmission to forecast epidemics and healthcare needs in LMICs, explore the potential impact of proposed interventions and estimate their impact in real-time. It will be fit to individual country surveillance data to support estimation of the reproduction number and projections will be made of the potential impact of alternative mitigation and suppression strategies, including household quarantine and social distancing, both generally and in vulnerable populations. The fit of the model to COVID-19 case count and mortality data collected after the implementation of various interventions will be used in real-time to evaluate their effectiveness in individual LMIC countries and the criteria for lifting of social distancing measures explored using the best fit model.",,2020,Imperial College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P30047,226120/Z/22/Z,Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS),"Southeast Asia (SEA) represents a weakness in global COVID-19 pandemic response because many countries do not have the required capacity to conduct advanced analysis to determine the potential threat of SARS-CoV-2 variants. Our aim is to develop and apply a multidisciplinary research platform for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby supporting local policy makers with evidence-based decision. We will deliver our proposal through four Objectives: - Establish a new SEA research platform that supports locally-led investigations evaluating the biology of emerging SARS-CoV-2 variants. - Employ state-of-the art structural biology to provide rapid prediction of the ability of new variants to evade host immunity and drugs. - Evaluate the impact of circulating variants of concern on antibody and T-cell responses in SEA populations, and the clinical consequences of infection. - Create a framework for effective communication and engagement with policy makers and the public concerning new virus variants and their potential to threaten public health. Our proposal will be delivered by the Vietnam and Thailand Wellcome Africa Asia Programmes, bringing together a multidisciplinary team in SEA (Indonesia, Singapore, Thailand and Vietnam), the UK and the USA. It will strengthen regional scientific capacity that can be rapidly deployed for future outbreak responses.",,2025,University of Oxford,3540614.38,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping | Community engagement | Communication",2022 +P30048,221003/Z/20/Z,"Characterization of SARS-CoV-2 transmission dynamics, clinical features and disease impact in South Africa, a setting with high HIV prevalence","Factors prevalent in Africa such as malnutrition, HIV, tuberculosis and limited access to healthcare, among others, may impact both transmission dynamics and disease progression associated with SARS-CoV-2 infection as well as the burden on the healthcare system and society.We aim to characterize key transmissibility and clinical features of and the antibody response to SARS- CoV-2 as well as to enhance surveillance for COVID-19, identify groups at increased risk of severe illness, estimate the disease burden of medically- and non-medically attended mild, severe-non-fatal and fatal illness and forecast the impact of the outbreak on the healthcare system and the society in South Africa. Particular emphasis will be given to HIV-infected individuals. The aims will be achieved through the implementation of shedding and household transmission studies, collection of sequential serum samples, enhanced facility-based (hospitals and clinics) surveillance among patients with mild and severerespiratory illness in well-established population-based surveillance sites where incidence can be calculated, and healthcare utilization and serological surveys in selected communities. In addition, digital surveillance (based on Google searches) will be used to complement virological surveillance and nowcasting and short-term forecasting (up to 4 weeks) will be implemented over the duration of the epidemic.",,2023,Wits Health Consortium (Pty) Ltd,2480516.15,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity | Other,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping,2020 +P30050,227698/Z/23/Z,Lifetime and Proximate Risk and Protective Factors for Young People's Mental Health and Wellbeing: Young Lives seventh survey round,"Young Lives (YL) is the largest and most comprehensive mixed-methods longitudinal study in the Global South following the lives of 12,000 young people dispersed across more than 80 rural and urban sites in Ethiopia, India, Peru and Vietnam for the past two decades. The study offers a timely opportunity to examine risk and protective factors for mental health from infancy to young adulthood, something which is unique in a comparable multi- country setting. Identical assessments and measures in several domains (physical and mental health, cognitive, social-emotional) have been implemented over a 20-year period. This proposal will enhance the design and data collection of the seventh YL survey round to capture the mental health and subjective well-being of the 22- and 29-years old YL respondents; to include a cortisol measurement from individual hair samples to be used as an ""objective measure"" of stress and to collect information about young people's experiences and responses to shocks, including climate-, covid-19- and conflict in the case of Ethiopia. We have the opportunity to contribute to the creation of unique open-access data providing an invaluable resource for our understanding of the lifetime and proximate risk and protective factors for young people's mental health and well-being.",,2025,University of Oxford,686342.34,Human Populations,Unspecified,Adults (18 and older),Rural Population/Setting | Urban Population/Setting,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P30052,228172/Z/23/Z,One Health Alternate Antimicrobial Resistance Monitoring System (AlARMS),"Leveraging the existing wastewater surveillance infrastructure built for polio and COVID-19 in South Africa, and, using a metagenomic approach, the proposed Alternate Antimicrobial Resistance Monitoring System (AlARMS) will delineate the burden of AMR from the longitudinal surveillance of the microbiome, resistome and mobilome in multiple One Health settings, comparing and contrasting genomic data from three sources: gut microbiota of vulnerable/at- risk humans, gut microbiota of their major, intensively-produced food animal sources, and associated wastewater microbiota. AlARMS will ascertain whether AMR in wastewater is representative of AMR in the microbiota of vulnerable/at- risk human (adding a step to the sewage-clinical AMR correlation by linking population-level AMR data) and animal populations and compare this to AMR in contemporary bacterial isolates from clinical and veterinary laboratories. The project will additionally explore the correlation/association (if any) between antimicrobial use (AMU) and antimicrobial residues in wastewater. AlARMS also includes an ethnographic study to ascertain socio-behavioural drivers of AMR and uses mathematical modelling to elucidate transmission dynamics. AlARMS may serve as early-warning and a proxy for conventional AMR surveillance systems in humans, food animals and the water, sanitation and hygiene (WASH) sector.",,2025,University of Kwazulu Natal,269452.55,Animals | Bacteria | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P30053,228344/Z/23/Z,Structural Investigation of Viral Surface Glycoproteins,"Viral surface glycoproteins are essential to viral replication cycles, mediating viral entry and escape. However, their surface exposure renders them key immunological targets and the centre of most vaccine designs. A comprehensive structural understanding of surface viral glycoproteins is therefore needed to understand their recognition by broadly neutralising antibodies (bnAbs) which are ideally produced in response to vaccination. This research will engage two high-priority viral pathogens, namely Human immunodeficiency virus (HIV) and Rift Valley Fever Virus (RVFV). The aims of this work will be two-fold. For HIV-1 there remain key questions surrounding its glycoprotein biology which have significant implications for future vaccine design. We will investigate these questions by cryo-EM of native HIV-1 Envelope (Env) glycoprotein. Secondly, RVFV vaccines are under trial and remain to be studied from a structural mechanistic standpoint. Therefore, I will seek to understand how the nChAdOx1 RVF vaccine is working at the molecular level to elicit protective antibody responses in patients.",,2026,University of Oxford,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P30054,228321/Z/23/Z,"The immunogenetics of humoral response, utilising COVID-19 as a model","Human genetic variation influences inter-individual immune responses. Throughout the COVID-19 pandemic, the UK Biobank (UKB) collected an array of serological data on subsets of participants both pre/post-vaccination, including up to 200,000 individuals. UKB also contains a wide range of anthropometric data, alongside various other key variables, such as social deprivation, age and immunosuppression, which are all known to influence immune responses. I will perform genome-wide association studies (GWAS) of vaccine-related outcomes, whilst understanding and carefully adjusting for potential confounding variables. My primary aim is to detect genomic regions associated with variable SARS-CoV-2 antibody titers following vaccine administration. Associations in known/novel loci and their pathways will be verified and validated via conducting allele-specific survival analyses, meta- analyses, further GWAS and through investigating COVID-19-related outcomes. Regions of interest will be fine mapped and where appropriate, the functional effect of variation will be determined, initially in silico. Relevant pathways could be targeted with adjuvants in order to upregulate post-vaccination antibody response, thus improving vaccine efficacy, and helping to tailor and improve the next generation of vaccine designs. Although this research will be conducted on COVID-19 related data, there is great scope for application to a wide range of vaccines targeting infectious and other diseases.",,2026,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies | Clinical characterisation and management,Disease susceptibility | Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis,2023 +P30055,219169/Z/19/Z,SOCIAL SCIENCE IN HUMANITARIAN ACTION PLATFORM: EXPANDING CAPACITY AND REMIT,"With the world facing repeated threats from disease outbreaks and with significant health and humanitarian crises engulfing regions, there is increasing recognition from humanitarian agencies of the value of social science knowledge and perspectives in contributing to operational preparedness and response efforts. In addition, there is a growing need for social scientists to assist with critical reflection on past responses and contribute to future learning, across all pillars of the emergency response. More targeted engagement with both agency staff involved in on-the-ground responses, as well as advocacy directed towards social scientists in order to improve their capacity to translate knowledge into actionable recommendations, could assist in mobilising a diverse and engaged community of practice. IDS, in collaboration with Anthrologica, has been a leader in such activities through the work of the Social Science in Humanitarian Action Platform, which has received acclaim for advocacy efforts and the production of synthesis briefings, such as for the current DRC Ebola outbreak. We are seeking funding to expand the work of the Platform in order to respond to an increasing demand for written and verbal briefings, for round table events in relation to crises, and for a fellowship scheme for practitioners and social scientists.",,2022,The Institute of Development Studies,541898.51,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience",,2020 +P30056,228080/Z/23/Z,The Effect of SARS-CoV-2 on Vascular Permeability,"The SARS-CoV-2 transmembrane accessory protein ORF7a has been modelled to bind to the T-lymphocyte LFA-1 integrin receptor. This receptor is usually involved in activation of T-lymphocytes and transmigration by interacting with the endothelial cell surface ICAM-1 receptor to facilitate firm adhesion. We are looking to study this interaction, to see if the in-silico models are accurate and if they have an observable effect on cell function. We will also assess if inhibition of the LFA-1:ORF7a interaction has any translatable benefit. Additionally, we will be analysing the SARS-CoV-2 nucleocapsid protein. This protein is involved in the encapsulation of the viral genome and uses host protein kinases to phosphorylate its SR rich region to affect binding affinities of the CTD and NTD to the viral genome, a process which is required during viral replication. Our approach to studying this interaction is to first work with recombinant ORF7a, assessing if the interaction can cause firm adhesion to endothelial cells in addition to doing in-vitro assays on nucleocapsid phosphorylation. Following on from this we will move onto live SARS-CoV-2 and in-vivo work to see if any results are translatable to the whole virus.",,2026,University of Nottingham,,Viruses,Not applicable,Not Applicable,Unspecified,Unspecified,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Clinical characterisation and management | Pathogen: natural history, transmission and diagnostics","Disease pathogenesis | Pathogen morphology, shedding & natural history",2022 +P30057,220179/A/20/Z,Understanding the impact of global change on animal-borne diseases,"We know little about how future climate change, habitat destruction, human population increases and greater globalisation processes will impact human zoonotic diseases. Here, I investigate the use of dynamic, seasonal host population models to better predict the impact of real-time environmental change on disease-carrying host species, within a general systems-dynamics, disease framework. Specifically, I will combine a mathematical compartmental disease model with a host population ecology model, within a spatial and temporal Bayesian framework. Using this approach, I will first model Lassa Fever using climate and land-use observations, collaborating with the Nigerian government. I will then augment my model to account for animal movement patterns and vector species abundances, to examine arboviral disease spread in North America. Then, I will integrate these threads into a general, dynamic modelling framework for zoonotic diseases, which will contain both the newly developed components and my previously developed model of human movement and behaviour. Working with the World Health Organisation, I will create short- and long-term disease forecasts for a set of high priority zoonoses. Once validated against human case data, these mechanistic models can be used to test interventions and create future disease management plans that are robust to upcoming global change.",,2026,Natural History Museum,899538.38,Animals | Human Populations | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures,2020 +P30058,228144/Z/23/Z,The 7th ANISE meeting 2023,"This grant is intended to support the 7th meeting of the ANISE (African Network for Influenza Surveillance and Epidemiology) network, which will be the first ANISE gathering of influenza and respiratory disease-focused experts in the continent of Africa since the COVID-19 pandemic. The African Network for Influenza Surveillance and Epidemiology (ANISE) is a network of laboratorians, epidemiologists, public health officials, clinicians, veterinarians, researchers, and policy makers who work together to strengthen the capacity for surveillance and research related to influenza and other respiratory viruses in Africa. This will be an opportunity for these experts to share their experiences since 2018 and lessons learned which can be applied to both preparedness for seasonal influenza and respiratory disease pandemics. The meeting will cover a variety of topics including disease burden, cost burden, economic impact of vaccines, influenza and vaccine policy, epidemiology, virology, and preparedness. There will also be several workshops offered on topics such as genomic surveillance and annual influenza season severity assessment. This will be an important forum to discuss the future direction of respiratory disease prevention, control and preparedness.This grant would fund conference activities such as a poster presentation session (venue hire, prizes) and travel grants for youth researchers.",,2023,Wits Health Consortium (Pty) Ltd,48424.69,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Unspecified,Not applicable,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,Epidemiological studies,Disease surveillance & mapping,2023 +P30059,225737/Z/22/Z,Human Infection Challenge Network (HIC-Vac),"HIC-Vac is a collaborative MRC/BBSRC-funded network led by Professor Peter Openshaw from Imperial College London. It was established in 2017, building on the UK's expertise in human challenge and has been remarkably successful in its aims of building a strong global team and funding seed projects in the UK and elsewhere (especially in LMICs). We now seek funding to be able to extend this success over the next 12 months, focused on work that aligns with Wellcome Trust's current aims and goals while we look to secure a more permanent future for our very productive coalition. Our key goals in this period are to enhance the engagement and utility of the network for LMIC-based researchers, report on the establishment of an intra-pandemic challenge study (SARS-CoV-2) with a view to preparing for future pandemics, set up the management of the Smart Practises document, liaise with the EU IMI INNO4VAC human challenge initiative, hold an Annual General Meeting, support early career researchers with a mentorship scheme and to continue our very active public engagement and communication activities.",,2023,Imperial College London,168576.79,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Clinical characterisation and management | Vaccines research, development and implementation",Clinical trials for disease management | Vaccine design and administration,2022 +P30060,220981/Z/20/Z,A comprehensive study of immunopathogenesis of SARS-CoV-2 infection,"Since December 2019 the emergence of severe acute respiratory infections (COVID-19) in China, caused by the new coronavirus SARS-CoV-2, has posed a huge threat to global health with fatality rates up to 10% in elderly patients. Almost 100% of patients showed bilateral patchy shadows or ground glass opacity in their lungs by chest CT scans indicating acute lung injury (ALI). Therefore, understanding the underlying mechanism(s) of ALI induced by SARS-CoV-2 is very important to inform vaccine safety and immunotherapeutic strategies. In this proposal, we will investigate the host immune responses and their association with severity of ALI in patient samples and animal models. We will bring together a team of experts with complementary expertise including immunopathology in coronavirus infections, up-to-date lab technologies, and know-how to ensure the feasibility of this study with the following goals: 1) defining SARS-CoV-2 specific serum profiles (epitopes) using yeast display antigen library 2) determining antibody functions including antibody-dependent enhancement (ADE) vs neutralizing activities in vitro assays 3) studying T cell (CD4 and CD8) responses to whole SARS-CoV-2 genome 4) evaluating ALI in response to live SARS-CoV-2 infection with or without passive immunity (antibody or T cells) generated from vaccine candidates in a humanized mice model.",,2023,Imperial College London,1124714.74,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P30061,225767/Z/22/Z,Developing an Evidence Generation Platform for Therapeutics with a focus on Low and Middle Income Countries (LMICs),"CEPI's vision is ""creating a world in which epidemics and pandemics are no longer a threat to humanity"". We were established with a mission to accelerate the development of vaccines, but we know that vaccines alone are not sufficient to achieve this vision. COVID-19 uncovered major gaps and opportunities in the therapeutics preparedness and response landscape, including: - A serious gap in end-to-end coordination - Fragility of upstream research efforts, including short-lived industry interest and insufficient access-friendly funding - Specific gaps along the value chain in: evidence generation, host-directed therapeutics, manufacturing scale-up, epidemic- and pandemic-ready policy and regulation, and advocacy for epidemic- and pandemic- specific procurement and country-readiness mechanisms We believe the global community would be well served by CEPI expanding into therapeutics. This would maximise the benefit for global health by utilising CEPI's well-regarded existing infrastructure, governance and processes. We propose a step-wise entry into therapeutics, starting with areas where existing CEPI capabilities can provide significant value for Therapeutics: evidence generation. Building on these entry points, CEPI will develop a longer-term strategy for how CEPI can best advance therapeutics preparedness and response, and, in doing so, help create a world in which epidemics and pandemics are no longer a threat to humanity.",,2023,Coalition for Epidemic Preparedness Innovations (CEPI),197791.23,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Norway,,"Therapeutics research, development and implementation",,2022 +P30062,224048/Z/21/Z,"Collaboration for Research, Training and Implementation in Critical Care in Asia and Africa (CCAA)","We envision that the project will equip an LMIC led community of practice with the infrastructure and capability to improve the quality of care for critically ill patients and healthcare providers using high value clinical and service data. The global COVID-19 pandemic has brought into focus the importance of critical care services and the impact of gaps in care quality on patient outcomes. This project builds upon the successes of our collaboration of LMIC investigator-led registries, which have contributed to data-driven health services research including pandemic preparedness and practice changing clinical trials. The outputs of this project directly align in vision with the WHO roadmap to strengthen health systems and enabling high quality LMIC research. The data research hub will provide unprecedented harmonised epidemiological and treatment data on critically ill patients comparable across income settings. The quality improvement interventions will improve care processes and generate methods scalable to other LMICs. This project will strengthen and sustain the foundations of a learning health system, whilst LMIC investigators develop the capabilities to lead research on policy, practice and population health.",,2025,University of Oxford,9982588.61,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,Unspecified,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies | Health Systems Research,Impact/ effectiveness of control measures | Disease surveillance & mapping | Health service delivery,2023 +P30063,223547/B/21/Z,Genomic Surveillance program for SARS-CoV-2: Consortium of India and Sri Lanka,"The global challenges posed by COVID-19 are best tackled through global cooperation between researchers, clinicians and funding agencies. One such challenge is generating timely, high-resolution monitoring of the SARS-CoV-2 viral evolution and using such data to guide public health response in a timely manner. The discovery of current variants of concern (VOC) in UK, South Africa and Brazil is because of a high quality sequencing program (UK) or vaccination related investigations (South Africa, Brazil). Indian SARS-CoV-2 Genomic Consortia (INSACOG) is revealing the possibility of local VOC driving fresh outbreaks. We proposes a network of satellite genomic sequencing MicroLabs in India, Bangladesh and Sri Lanka that will be integrated by virtual cloud-based workflows as well as physical linkages to national MegaLabs for quality assurance and operational support. This would help scale up global monitoring of emerging SARS-CoV-2 strains in one of the world's most populous region and guide global R&D efforts for COVID-19 diagnostics, vaccines and therapeutics. Given the relevance of SARS-CoV-2 surveillance to especially the diagnostics and health systems pillars of WHO's ACT- Accelerator, partners such as Wellcome Trust can play an important role in furthering this effort. There is an urgent need to create distributed local capacity via MicroLab hubs.",,2024,University of Colombo,520180.86,Disease Vectors,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,Unspecified,,,,Sri Lanka,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P30064,221303/Z/20/Z,Managing COVID-19 epidemics in low- to middle-income and crisis-affected settings: Epidemiological and economic evaluation,"The COVID-19 pandemic is rapidly escalating and poses a potentially catastrophic threat to low and middle-income countries (LMICs) as well as crisis-affected populations. To support evidence-based, real-time decision- making by countries, donors, humanitarian actors and other stakeholders, the London School of Hygiene and Tropical Medicine (LSHTM) hereby proposes a six- month multi-disciplinary project. The project is built around three Workstreams: (1) Evaluation of the health, fiscal and macro-economic impact of response options; (2) Global analysis; and (3) Technical support to decision- makers and local researchers. Specific activities (and associated deliverables) include the following: - Improve global data collation and capacity for economic analysis around COVID-19 - Evaluate the health and economic implications of COVID-19 response options using micro-economic models - Quantify the macro-economic consequences of COVID-19 response options - Predict the transmission and mortality of alternative shielding options for high-risk populations - Provide a regular series of global COVID-19 health impact, resource needs and cost estimates - Advise LMIC governments, donors and humanitarian actors on COVID-19 strategy - Support technical guidance and coordination for humanitarian actors - Support LMIC economists to provide local evidence on COVID-19 responses We propose to undertake the above largely through desk-based work from London over a period of 6 months (Apr-Sep 2020).",,2021,London School of Hygiene & Tropical Medicine,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Economic impacts,2020 +P30065,221013/A/20/Z,"Serological studies to quantify SARS-CoV-2 population infection risk in Singapore, Hong Kong and Thailand","We propose a prospective serological study to investigate the incidence of SARS-CoV-2 infection in the general population in three Asian settings: Singapore, Hong Kong and Thailand. The study will aim to measure the age- specific seroprevalence and incidence of SARS-CoV-2 infection at 3 time points, each 6 months apart. Age-specific incidence estimates will be applied to the census population to obtain numbers of infections in the population at each time point. These estimates will be compared with external data on COVID-19 hospitalisations and deaths in each setting, to calculate age- specific infection-hospitalisation and infection-fatality ratios. SARS-CoV-2 antibody kinetics will be defined by studying changes in antibody titres over time. Risk factors for infection will be studied by comparing SARS-CoV-2 seroconverters and non-seroconverters with respect to epidemiological exposures. This study will provide crucial information regarding population exposure and SARS-CoV-2 transmission dynamics, and will provide a complete picture of the relationship between clinically apparent and asymptomatic infections.",,2025,National University of Singapore,514932.48,Human Populations,Asian,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Western Pacific,Unspecified,,,,Singapore,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Immunity | Disease surveillance & mapping,2020 +P30066,227714/Z/23/Z,Survival and adaptation of viruses within respiratory droplets: a combined molecular biological and biophysical study,"The recent Covid-19 pandemic has highlighted significant gaps in our understanding of respiratory virus transmission. Respiratory viruses must survive within respiratory droplets in order to transmit and infect others, but we have little understanding of the stresses they are exposed to and how the virus particles interact with droplet components such as mucus. Using a vaccine strain of influenza, I will initially explore how viral infectivity depends on various physical parameters such as pH, humidity, salt concentration and the presence of mucus in bulk solution (flasks). By using genetic manipulation of several viral structural components, I will then explore potential adaptions influenza may have made to withstand these environmental stresses. In parallel, I will develop a model respiratory droplet to investigate how these findings of viral survival in bulk solutions translate into this more realistic environment for understanding air-borne transmission. Here, extra complications such as the development of a core- shell structure due to mucus accumulation at the air-water interface may have important biophysical implications. These studies should give us deeper insight into the mechanisms of and constraints on viral transmission, forming a basis for improved infection control methods and policies.",,2025,University of Edinburgh,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Environmental stability of pathogen",2022 +P30067,220985/Z/20/Z,COVID-19 Intervention Modelling for East Africa (CIMEA),"COVID-19 is a global threat to health, with many countries reporting extended outbreaks. To date 9 countries in Africa have recorded infection and it seems imminent that East Africa will have introductions and onward transmission. The SARS-CoV-2 virus (the aetiological agent of COVID-19) spreads rapidly (R0~2, serial interval about 1 week), and hence control will be difficult. National plans for dealing with this public health emergency will benefit from predictions of the expected rate, distribution and extent of spread in countries throughout the region, and on the likely impact and feasibility of isolation and contact tracing interventions. We will support the emergency preparations through bespoke modelling, incorporating known demographic population structure, age-related contact patterns and existing mobile phone population movement data. In Uganda and Kenya we will collect epidemiological, genomic and behavioural data through health facility surveillance, household follow-up and contact studies to quantify uncertainties of SARS-CoV-2 virus epidemiology and contact patterns in well and unwell individuals. Results from the study will be rapidly communicated to the relevant authorities, and modelling code and analysis, and data including sequences, placed in the public domain in near real-time. This project could have lasting impact on the role of research in policy decisions.",,2024,University of Warwick,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2020 +P30068,313353/Z/24/Z,International scientific conference on strategies for the prevention and management of Mpox in Africa and the Democratic Republic of the Congo (DRC),"Wellcome received a time-sensitive funding request from the Africa Centres for Disease Control and Prevention (Africa CDC) to support the upcoming International Meeting on Mpox in Africa, scheduled for April 11-12, 2024, in Kinshasa, Democratic Republic of the Congo (DRC). The request, USD 318,000, which was initially directed to CEPI, was shared with Wellcome to explore the possibility of co-funding the event. The International Meeting on Mpox in Africa is a direct response to the escalating Mpox outbreak in the DRC and neighboring countries, which has resulted in 3,941 suspected cases and 271 fatalities (CFR 6.9%) since January 2024, with a disproportionate impact on children under 15. Africa CDC and the DRC government are jointly organizing this conference to bring together key stakeholders from affected and at-risk African countries, continental and regional bodies, funders, and global health partners to address the crisis. The primary objectives of this conference are to share the latest research and insights on Mpox, review and enhance existing response frameworks, foster partnerships, and develop a comprehensive action plan for mpox surveillance, control, and prevention across the continent. This funding request was considered in recognition of the urgency and strategic importance of this meeting, and the critical role Wellcome has played in driving global momentum towards responding to Mpox in DRC. Upon discussion with CEPI and Africa CDC, the funding ask to Wellcome is up to $100,000 with the remainder covered by the two partners. """,,2024,African Field Epidemiology Network,100052.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Uganda,,"Policies for public health, disease control & community resilience | Health Systems Research",Approaches to public health interventions | Policy research and interventions | Health leadership and governance,2024 +P30069,302473/Z/23/Z,Rational Design of Cross-protective T cell Vaccines,"Keywords: Vaccines, T-cells, Immunology, Virology, Cross-reactivity, Coronavirus, Machine Learning, Proactive Vaccinology, T-cell Receptor. The fundamental problem when designing vaccines for variable viruses is how to induce immunity that can recognise and protect against the breadth of globally circulating viral strains. T-cells have an inherent ability to cross-recognise a wide range of viral sequences because they recognise short linear peptides, in particular within essential conserved non-structural proteins. Challenging the immunological paradigm that T-cells alone cannot block infection, I recently demonstrated that pre-existing T-cells targeting the most conserved proteins across the coronavirus family, the replication-transcription complex (RTC), correlate with protection from detectable SARS-CoV-2 infection in exposed seronegative individuals (Swadling.Nature.2022). This suggests cross- species protection from infection by T-cells alone and that specificity is linked to protective efficacy. It is essential now to identify precisely which epitopes within the RTC are mediating this cross-protection so that we can: 1) integrate analysis of the viral sequence, TCR repertoire, and functional cross-reactivity at these epitopes to elucidate the fundamental rules underpinning T-cell cross-reactivity; 2) use these epitopes in pan-coronavirus vaccines. Ultimately, I will test the hypothesis that 'rational design of vaccines to induce cross-protective T-cell immunity will lead to effective infection blocking vaccines for variable viruses'.",,2032,University College London,2898841.16,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2024 +P30070,303026/Z/23/Z,How using glycans vs. proteins as receptors affects the mechanism of viral entry,"Viruses typically employ either glycans or proteins as receptors. However, certain viruses, such as influenza A and coronaviruses, have the ability to alter their receptor specificity-from a glycan to a protein receptor, and in some instances, even bind both. These receptor transitions can correlate with changes in viral tropism, influencing disease severity and facilitating host jumps. Yet, little is known about the effects the receptor type have on the mechanism of viral entry. I will use my background in studying the structure and evolution of viral glycoproteins to compare at the molecular level how different receptor types are recognised structurally, how they dictate interaction avidity, and affect the mechanisms of viral fusion. We will build on my pilot data on interactions between haemagglutinins of bat-like influenza viruses and their non-canonical protein receptors MHC-IIs, and new structural insights into coronavirus spikes, to investigate and compare mechanisms of binding between influenza haemagglutinins and coronavirus spikes with glycan and protein receptors. This will bring new insights into the mechanisms of viral entry and reveal possible evolutionary pathways associated with changes in receptor tropism, enabling informed monitoring of emerging viruses and contributing to pandemic prevention.",,2032,University of Oxford,3224490.36,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2024 +P30071,218773/Z/19/Z,Lassa fever near-patient PCR and haemostasis diagnostics,"Lassa fever is a life-threatening viral haemorrhagic fever and a major public health burden in West Africa, causing tens of thousands of cases annually with high patient mortality. The signs and symptoms of LF mimic common febrile illnesses in the early phase of the disease which makes diagnosis of the disease difficult. Severe disease is characterized by bleeding, the pathogenesis of which remains unexplained. Clinical patterns of bleeding and data from the 1980s have suggested that platelet dysfunction may be a major cause. This research project will study Lassa fever in adults and children in Sierra Leone. This project will develop and evaluate novel LASV assays in portable RT-qPCR systems to facilitate early diagnosis at the point of need, and will investigate the haemostatic changes in Lassa fever using modern assays, focusing especially on platelet dysfunction. We will assess whether thromboelastometry and coagulopathy biomarkers correlate with bleeding and disease severity. Flow cytometry will further improve understanding of the underlying mechanism(s) responsible for the coagulopathy. This research has the potential to achieve rapid impact, strengthen laboratory capability and provide new international academic collaboration in a neglected disease designated a priority for research by the World Health Organization.",,2025,University of Sierra Leone,231209.92,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Unspecified | Not applicable,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Sierra Leone,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Diagnostics | Prognostic factors for disease severity | Disease pathogenesis,2021 +P30073,221012/Z/20/Z,"The African coaLition for Epidemic Research, Response and Training, Clinical Characterization Protocol (ALERRT CCP)","As part of the response to the emergence of COVID-19, the World Health Organization Africa Regional Office is organizing various Infection Prevention and Control (IPC) and critical care training activities targeted at Low and Middle-Income countries (LMICs) in Africa. While the initiatives taken by WHO/AFRO are critical, training for research into the disease also needs to be targeted at the same LMICs, because being an Emerging Infectious Disease, we need to ""learn-as-we-go"". Clinical research on COVID-19 will have to be closely integrated with the IPC, clinical care, and epidemiological training activities, including use of the WHO First Few X (FFX) Cases and contact investigation protocol for COVID-19. ALERRT proposes to work closely with the WHO/AFRO and Africa CDC and existing networks and structures across Africa and globally to provide the fore-mentioned clinical research training and support. ALERRT is a member of the Global Federation - ISARIC, which has developed a Clinical Characterization protocol for COVID-19. This protocol been endorsed by the WHO and is currently being used in China and across the UK and Europe.Being already established and conducting activities in sub-Sahara Africa, the ALERRT network has the capacity to effectively implement the proposed project.",,2024,Kwame Nkrumah University of Science and Technology,1848083.36,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Ghana,,Clinical characterisation and management | Infection prevention and control,,2020 +P30074,222895/Z/21/Z,"Assessing the role of care homes as community reservoirs, and potential sentinel sites for the enhanced surveillance of infectious disease.","The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a devastating effect on adults living in long term care: it's estimated that this population accounted for at least 40% of COVID-19 related deaths in the UK during the first 3 months of the pandemic. COVID-19, like many other infectious diseases, can spread silently - particularly among older people who are often infectious without displaying any symptoms. In care homes, this results in explosive outbreaks which are difficult to control. In order to detect infectious organisms before they cause outbreaks, it's important to understand where the pathogens accumulate and how they are distributed. Since viruses and bacteria can be found on surfaces, in the air and in waste water, sampling the environment will provide clues about how they spread so effectively in care homes. This study will investigate how the SARS-CoV-2 virus spreads around care homes during outbreaks. We will take regular environmental samples alongside diagnostic tests for staff and residents, and epidemiological information about the setting and its population. Using the findings from this study we will build a mathematical model to assess the best way to monitor care homes for the emergence of infectious diseases.",,2023,University of Bristol,,Human Populations | Environment,Unspecified,Adults (18 and older) | Older adults (65 and older),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Disease surveillance & mapping,2020 +P30075,218537/Z/19/Z,Strategic endgames - modulating transcription termination to control gene expression,"Viruses employ various approaches to avoid host cell defence-mechanisms. In Herpes Simplex Virus 1 (HSV1) and Influenza A Virus (IAV) these include strategies to inhibit transcription termination. This leads to non-terminated readthrough transcripts, likely nuclear retained and untranslated. Exactly how viruses inhibit transcription termination, and how this promotes their survival and efficacy is currently unclear. Using my experience and expertise in transcription termination, I propose to systematically analyse the mechanism by which IAV alters 3' end processing transcription termination and determine how this affects host gene expression. I will use biochemistry, molecular biology and structural biology, to identify the termination components affected by IAV, and reverse genetics to identify the IAV-component effecting termination inhibition. I will also employ sequencing of fractionated, cellular and ribosome-associated RNA to examine how virally- induced termination defects perturb mRNA-export and translation, as well as cell biology and genetics to identify the mechanisms and signalling cascades through which this change is realised. Finally, I will perform orthogonal studies in budding yeast to identify molecular mechanisms that can modulate the activity of transcription termination and RNA processing factors. Overall, my programme will scrutinize an under-explored yet fascinating mechanism to alter gene expression through modulation of transcription termination.",,2026,King's College London,1635673.46,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Other,Unspecified,,,,,,,,Pandemic-prone influenza | Other,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P30076,226141/Z/22/Z,G2P - Global Knowledge Exchange to Enable In Country Risk Assessment of SARS CoV-2 Variants,"SARS CoV-2 continues to evolve. Novel variants are driven by high levels of global transmission and viral replication, sustained selection pressures imparted by existing immunity acquired through natural infection and vaccination, and increasing use of antivirals. Building on G2P-UK, established working partnerships between teams in the UK, Africa and India, and an ethos of free knowledge exchange, we outline 4 inter-related aims that will enable and prepare G2P-Global to evaluate the significance of emerging viral variation across 3 continents. We will: 1) Implement standardized methodologies that enable rapid in-country risk assessment of the biological and antigenic properties of SARS-CoV-2 variants of concern (VOCs), providing real-time data for guiding infection control and vaccination policies; 2) Undertake discovery-led molecular, cellular and in vivo (hamster) analyses of variant phenotypes to address the mechanistic basis for how the virus can evolve while balancing immune escape with the maintenance of efficient respiratory transmission; 3) Assess the potential for spill-overs into domesticated and wild animal species and subsequent reservoir seeding; 4) Establish communications networks and laboratory resources that will build technical and logistical preparedness enabling G2P-Global partners and additional collaborators to undertake in-country virological assessments of future respiratory virus outbreaks, and associated virus variants.",,2026,Imperial College London,3777984.95,Animals | Human Populations,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities",2023 +P30077,224494/B/21/Z,Long-term consequences of Zika virus infections during pregnancy for school- aged children and their families in Brazil,"Using unparalleled epidemiological, administrative, and social science data continuously collected from 2015 onwards in Brazil, this collaborative proposal aims to define the prognosis and learning needs of school-aged children with prenatal exposure to Zika virus (ZIKV) and the long-term health and social impacts for families of children with Congenital Zika Syndrome (CZS). Through four linked work packages, we will: (i) define the natural history of CZS in the first 12 years of life, including the frequency of late- onset manifestations, hospitalizations, and deaths, (ii) compare neurodevelopment and learning-related outcomes in children with and without CZS, (iii) evaluate long-term consequences of CZS for families, including implications of COVID-19, and (iv) critically interrogate the experience of families engaging in research and data sharing initiatives during and after public health emergencies. To achieve these aims, we are requesting resources to perform comprehensive clinical and neurodevelopmental assessments in the Microcephaly Epidemic Research Group and ZIKAIFF Pediatric Cohorts in Pernambuco and Rio de Janeiro states, undertake a nationwide individual participant data meta-analysis of ZIKV-related clinical and neurodevelopmental outcomes among children in the Zika Brazilian Cohorts Consortium, link large- scale nationwide electronic health and social records in the CIDACS/Fiocruz Zika Platform, and conduct qualitative research with key stakeholders.",,2030,Insituto de Apoio à Fundação Universidade de Pernambuco (IAUPE),1852304.47,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,Brazil,,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Policy research and interventions | Indirect health impacts,2023 +P30078,226061/Z/22/Z,An Open Source Framework for Rift Valley Fever Forecasting,"Rift Valley Fever (RVF) is a complex disease with devastating public health and economic costs. It is transmitted directly from livestock to people and is maintained via mosquito transmission in livestock populations. As a zoonotic disease with a vector component, outbreaks of RVF are tightly linked to climatic and environmental conditions. Statistical modeling approaches have been developed to forecast RVF in Africa, but performance has been inconsistent across regions, with higher predictive accuracy in East Africa than in Southern Africa. Current continent-wide models, which use the Normalized Difference Vegetation Index (NDVI) to predict RVF activity, do not capture local attributes, such as livestock density and land cover, which may explain differing performance. We have assembled a team that includes local South Africa (RSA) government stakeholders, and co-created a tool for RSA that builds on previous work to create an RVF Early Warning System for RSA. Our goal is to package this new, open, locally customizable tool developed for RSA for deployment to other impacted regions. The intent is that end-users (farmers, farmer associations, others) would be forewarned when to vaccinate their livestock against RVF, a month to three months in advance of potential RVF activity.",,2027,EcoHealth Alliance,600204.71,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Bunyaviridae,,,,,,,,,Rift Valley Fever,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,Infection prevention and control,Restriction measures to prevent secondary transmission in communities,2022 +P30079,225081/Z/22/Z,Disentangling viral RNA structural dynamics and RNP condensation in a patient- derived model of airway epithelial infection,"My research vision ultimately aims to identify targeted treatments for respiratory viral infections, through a detailed understanding of the molecular interactions between the virus and host. Here, I propose to study influenza A virus and SARS-CoV-2 and the role of viral structure and viral- host ribonucleoprotein (RNP) condensation. In particular I will assess the impact on the viral infection cycle and also differences in host responses from normal and smoking-damaged lungs. My hypothesis is that interactions between dynamic viral RNA structures and host RBPs within airway epithelial cells are crucial to viral RNP condensation and the molecular response to infection, and that they are impaired in disease. I have three key goals: - Establish my functional genomics molecular toolkit in a new patient-derived airway epithelial cell infection model system and obtain global measurements of structure and condensation - Develop a new suite of methods to characterise the dynamics of viral RNA structures and interactions with RBPs at single molecule resolution - Derive an in silico model of RNP condensation and clinical phenotype through iterative integrative computational analysis and machine learning methods and predict high-confidence potential therapeutic targets.",,2028,University College London,1336291.85,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Pre-clinical studies",2023 +P30080,228129/Z/23/Z,DNA-based delivery of antiviral antibodies for Zika and Influenza prevention,"RenBio proposes a two-pronged approach to evaluate the applicability of MYO Technology for DNA-based antiviral antibody delivery, using antibodies directed against Zika virus (ZIKV) and influenza A virus (IAV). The MYO Technology platform uses intramuscular electroporation to efficiently deliver antibody-encoding plasmid DNA to muscle cells, which then produce and secrete the antibody, delivering it to systemic circulation. Multiple proof-of-concept animal studies, including an IAV challenge study, have demonstrated efficacy with this approach, which has the potential to greatly improve access to antibodies by reducing costs and dosing frequency. The two aims of this proposal are to 1) complete IND-enabling preclinical activities to support the development of a potent anti-ZIKV antibody, and 2) evaluate the potential for the delivery of cocktails of anti-IAV antibodies for the prevention of disease. The first aim would complement an ongoing program partially funded by the US government via the Defense Advanced Research Projects Agency and conducted in collaboration with academic partners. The second aim would result in an assessment and mitigation of technical hurdles associated with DNA-based delivery of antibody cocktails, with proof-of-concept data generated in animal models of IAV infection. These two aims have the potential to significantly impact ZIKV and IAV disease prevention.",,2025,RenBio,2881210.94,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae | Orthomyxoviridae,Other | Unspecified,,,,,,,,Zika virus disease | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,Innovation,,,United States of America,,"Therapeutics research, development and implementation",Pre-clinical studies,2024 +P30081,221377/B/20/Z,Funding of Covid-19 R&D; Priorities in Africa,"Success against the Covid-19 pandemic requires a transdisciplinary approach incorporating social sciences and humanities, economic research and health systems research. It also requires access to funding. The African Academy of Sciences (AAS), through its hosted AESA Platform, acts as Secretariat for this Fund for Covid-19 R&D priorities in Africa. This Fund is seeking proposals against identified priorities; coordinating a network of researchers working on Covid-19 R&D to build a clinical research and trials platform for Africa; and taking a longer-term view to address pandemic preparedness in research actions. The Fund is open to multiple priority areas for research and development, including: - Epidemiological studies Studies to define disease severity and susceptibility of particularly groups at high risk of severe infection; the role of different age groups in transmission; the impact of control and mitigation measures; and to predict the most effective interventions. - Clinical management Studies to define the natural history of Covid-19 infection including the identification of prognostic factors for severe disease and the identification of vulnerable groups; and studies to improve the clinical outcome of Covid-19, including strategies to improve the processes of care. - Infection prevention and control Studies to assess the effectiveness, in both healthcare and community settings, of movement control strategies in preventing secondary transmission and of personal protective equipment in reducing the risk of transmission. - Candidate vaccines, diagnostics and therapeutics Clinical trials of potential treatments and preventative strategies, facilitated by the recent AESA programme launched as the Clinical Trials Community online platform. - Ethical considerations for research Studies on culturally appropriate approaches to the ethical, social and legal issues prevalent in emergency situations, such as presented by Covid-19. - Social sciences in a pandemic response Engagement to bring community voices to decision-making processes, to understand non-intended consequences of pandemic-control decisions and to understand contextual vulnerability; and studies to mitigate impacts of the socio-economic and political externalities of Covid-19.",,2024,Science for Africa Foundation (SFA),740685.65,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Kenya,,"Epidemiological studies | Clinical characterisation and management | Infection prevention and control | Therapeutics research, development and implementation | Vaccines research, development and implementation | Research to inform ethical issues | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures | Health Systems Research","Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping | Supportive care, processes of care and management | Clinical trials for disease management | Restriction measures to prevent secondary transmission in communities | Barriers, PPE, environmental, animal and vector control measures | IPC in health care settings | Research to inform ethical issues in Research | Research to inform ethical issues related to Public Health Measures | Research to inform ethical issues in Clinical and Health System Decision-Making | Approaches to public health interventions | Community engagement | Indirect health impacts | Social impacts | Health service delivery",2021 +P30082,225170/Z/22/Z,Characterisation of a GMP SARS-CoV-2 Delta variant for human challenge,"SARS-CoV-2 continues to spread in spite of vaccination due in part to the high transmissibility of the prevalent delta variant. The factors predisposing to breakthrough infection are unknown and correlates of protection remain unclear. Human challenge studies are uniquely able to control for differences in virus strain, dose and exposure to investigate these factors. Safety in seronegative participants challenged with a D614G pre-alpha strain was recently shown and a new GMP delta challenge agent is now being manufactured. We therefore aim - To establish an optimised controlled human infection model using a GMP SARS-CoV-2 Delta (B.1.617.2) challenge agent, characterising virological and immunological readouts therein to enable further assessment and development of COVID-19 vaccines - To identify the determinants of vaccine breakthrough infection and correlates of protection in antigenically- experienced individuals These will be achieved by challenging vaccinated individuals with Delta and optimising the attack rate by sero-screening and dose-escalation. Using these optimised conditions, 3 groups will then be compared: - vaccinated, uninfected individuals, Delta-challenged; - vaccinated, previously-infected, Delta-challenged; and - vaccinated, uninfected, pre-Alpha-challenged. Thus, host determinants of differential disease and virological outcome will be identified in the context of pre- existing immunity by vaccination and/or infection to define correlates and mechanisms of homologous and heterologous protection.",,2025,Imperial College London,8051015.84,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Disease models | Characterisation of vaccine-induced immunity,2022 +P30083,227120/Z/23/Z,An investigation into transmission and total cases of Crimean-Congo haemorrhagic fever (CCHF) in Uganda,"Crimean-Congo haemorrhagic fever virus (CCHFV) is endemic in Uganda, shown by high seroprevalence in humans and animals. Sporadic outbreaks are regularly reported in humans in areas considered to be at highest risk within the Ugandan cattle corridor. However, recently we have detected cases of undiagnosed CCHF in patients presenting with acute febrile illness in other parts of the country. The incidence and prevalence of CCHF across Uganda and the extent of the health burden is not known. In this study, we will carry out a country-wide, longitudinal seroprevalence study to assess parts of the country most at risk. We will investigate risk factors using quantitative and qualitative approaches. With a mechanistic mathematical model, I aim to investigate the burden of CCHFV infection in Uganda. This will help to inform policy makers about the burden of CCHF on the health care system and will inform about the need to improve diagnostics for viral infections, thereby reducing misdiagnosis. Additionally, the model can later be used to show the effectiveness of interventions against infection with CCHFV.",,2025,University of Glasgow,,Human Populations,Black,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease surveillance & mapping,2022 +P30084,226438/Z/22/Z,"Proposal for Updating and Finalizing WHO Research and Development (R&D;) Roadmaps for Lassa, Nipah, and Zika viruses","Research and development (R&D) roadmaps are a valuable tool for guiding R&D efforts to prevent and control high-priority pathogens with epidemic potential. From mid-2017 through 2018, with funding from Wellcome, CIDRAP developed R&D roadmaps for Lassa, Ebola/Marburg, and Nipah viruses. From 2019 through 2021, CIDRAP developed a similar roadmap for Zika virus with funding from WHO. Draft roadmaps were submitted to WHO, but were not published owing to capacity restraints during the COVID-19 pandemic. The need for the roadmaps has not diminished and all parties involved are interested in finalizing three of them (for Lassa, Nipah, and Zika viruses); however, before they can be published, each requires thorough review and updating to incorporate recent scientific advancements and developments in the respective fields. CIDRAP proposes to conduct an 11-month project aimed at publishing the Lassa, Nipah, and Zika virus R&D roadmaps on the WHO website. Key activities include updating the roadmaps; reinvigorating the previously established expert taskforces for each roadmap and ensuring appropriate geographic balance of members; conducting in-person taskforce consultations; finalizing and delivering the roadmaps to WHO; supporting roadmap launch activities (depending on timing and resources); and preparing manuscripts for publication in open-access journals to share results of this work.",,2024,University of Minnesota,357157.49,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Arenaviridae | Flaviviridae | Paramyxovirdiae,,,,,,,,,Lassa fever | Zika virus disease | Nipah and henipaviral disease,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,"Policies for public health, disease control & community resilience | Health Systems Research | Research on Capacity Strengthening",Policy research and interventions | Health leadership and governance | Cross-cutting,2022 +P30085,226002/Z/22/Z,"Rates, determinants, and transmissibility of respiratory virus re-infections","Multiple reinfections are characteristic of many respiratory viruses and a critical determinant of endemicity in human populations. However, there is a paucity of data on the rates and determinants of reinfections, and the importance of reinfections in chains of transmission. This project will investigate reinfection for three common respiratory viruses - SARS-CoV-2, influenza, and respiratory syncytial virus - within the household setting. I will determine the frequency and timing of reinfections independent of clinical presentation; identify viral genomic and host immunological characteristics of reinfections; and determine the factors that influence the transmission potential of reinfections. My proposal includes a three-year household cohort study in coastal Kenya, with intensive respiratory sampling for RT-PCR and genomic sequencing, and bimonthly blood samples to assess immune status and serological responses relating to reinfection. I will estimate the rate of immunity loss and reinfection infectiousness in relation to age, virus load, symptoms, and host immunity, and use mathematical models to explore the transmission dynamics and intervention impact building on the new understanding from this research.",,2031,Kemri-Wellcome Trust Research Programme,2660297.85,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza | Other,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Kenya,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease susceptibility | Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences",2023 +P30086,223271/Z/21/Z,Leveraging COG-UK expertise to support the global dissemination of SARS-CoV-2 genome sequencing,"Control of the COVID-19 pandemic depends on the development and equitable roll-out of vaccines that remain effective over time. But the evolution of SARS-CoV-2 variants that exhibit variable degrees of immune evasion, and other characteristics including greater transmissibility and/or lethality, threaten to undermine our ability to control COVID-19. It is widely accepted that vaccines will need to be altered over time as the virus mutates. Effective vaccine re-development is dependent upon the availability of global viral sequence data, but there is a lack of sequence data for much of the world, including low, middle and high-income countries. The COVID-19 Genomics UK Consortium (COG-UK) (including the Wellcome Sanger Institute) will leverage its expertise to develop a comprehensive global learning programme on SARS- CoV-2 genome sequencing (COG-GLOBAL). This will be achieved by working with experienced on-line educators. Specific aims include the development of an open access, online modular global learning programme on SARS-CoV-2 sequencing and analysis, allowing users to follow pathways of learning according to professional expertise (laboratory scientist, clinical practitioner, data scientist & epidemiologist, bioinformatician or policy maker); and the development of train-the-trainer courses in collaboration with the Wellcome Connecting Science Advanced Courses, Wellcome Africa and Asia Programmes, and other contributors.",,2023,University of Cambridge,698708.08,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Health Systems Research","Pathogen genomics, mutations and adaptations | Health information systems | Health workforce",2021 +P30087,220214/Z/20/Z,Unprecedented Movement to drive a Unified Rwandan Initiative for National ZEBOVAC Immunization,"The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) and the recent identification of Ebola cases in the cities of Goma and Bukavu (which border Rwanda) are of particular concern and have prompted the Rwandan Government to take control measures for preventing cross- border spread of EVD. As demonstrated by the current outbreak, purely reactive measures may be insufficient to fight Ebola. Prophylactic approaches are needed that can prevent emergence of EVD in previously unaffected areas. We propose to conduct a large-scale vaccination campaign targeting 196,000 individuals living and working in border-proximate areas; a clinical trial to evaluate the immunogenicity of the AD26.ZEBOV, MVA-BN-Filo vaccine in 2,000 people; and a clinical trial to evaluate the safety of the vaccine among 2,000 pregnant women in the context of this new framework of Ebola prevention. These 3 programs will together generate a large cohort that can be revisited for a long term follow up study to assess long term immunogenicity at different times following vaccination; an evaluation of a potential effect of booster doses and the optimal strategy for booster administration; and an evaluation of long term assessment of effectiveness using a test-negative case control study design.",,2022,Center for Family Health Research,1992815.14,Human Populations,Unspecified,Adults (18 and older),Unspecified,Pregnant women,Unspecified,Clinical,Unspecified,Filoviridae,,,,,,,,,Ebola virus disease,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Rwanda,,"Vaccines research, development and implementation",Clinical trial (unspecified trial phase) | Vaccine design and administration | Characterisation of vaccine-induced immunity,2020 +P30088,228331/Z/23/Z,Investigating the spatial landscape of influenza-induced anti-viral immunity in the lung.,"Influenza A virus (IAV) vaccination strategies and immunity generated from natural infection with IAV rarely provide long-lasting immunity. This is partly because the surface viral proteins that antibodies target are prone to change. Therefore, antibody-mediated protection against one IAV infection is not always protective against future variants. Thus, it is important to understand how the immune system can target conserved viral aspects that are shared between strains. There are two main strategies to generate generalised immunity and I will investigate the potential of both. Firstly, I will investigate how resident memory T-cells, a type of immune cell that stays in the lung post-infection and targets conserved IAV proteins are retained after infection. Using a modified IAV, I will look at how signals required for their retention are maintained. This may allow us to improve their retention and promote longer-lived protection. Secondly, I will investigate how IAV infection causes a window of non-specific anti-viral immunity. Using novel mouse models, I will interrogate which immune cells control this behaviour and how they do this. Moreover, I want to know whether the antiviral effect is limited to regions of the lung that have previously seen IAV infection and whether this can be boosted.",,2026,University of Glasgow,,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2023 +P30089,224648/Z/21/Z,Preclinical Studies on Oral SARS-CoV-2 MPro Inhibitors,"Our company core values are to make a significant contribution to improving the quality of life and health of people around the world. We felt compelled to leverage our expertise in SBDD to discover an effective treatment for COVID-19. Our focused Not-for-Profit program, supported by our parent company Sosei, has employed SBDD to rapidly identify a potential clinical candidate to be used as an anti-viral treatment. This fulfilled our initial objectives, completing this stage of the program. Having successfully identified compounds potentially suitable to be used as oral agents to treat COVID-19, we are well placed to progress compounds into preclinical development, after which we anticipate the program to be progressed by interested parties with expertise in antiviral clinical development. The UK Antiviral Task Force have confirmed a qualified candidate is required for further funding to be potentially be made available. Given the urgent clinical need for antiviral agents, we are seeking funding to progress our molecules up to the potential nomination of a pre-clinical candidate. We have designed a concise program of in vitro and in vivo profiling activities encompassing tolerability, safety, selectivity and efficacy to proceed rapidly, considering the likely desired dose regimen and route of administration.",,2023,Heptares Therapeutics Ltd,687152.49,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P30091,219634/A/19/Z,"Consolidating practice in social science research for Ebola, DRC.","The response to the Ebola epidemic in North Kivu and Ituri provinces, Democratic Republic of Congo has been described as one of the most complex that national and international communities have had to face.Given the complexity of this protracted epidemic, social science research has become a critically important part of the response in order to help contextualise strategies, investigate social determinants of infection, and inform understanding and reception of interventions employed for outbreak control. To routinely generate this intelligence, an innovative solution has emerged in the form of the Cellule d'Analyse en Sciences Sociales. UNICEF-funded, this group is made up predominantly of local and national social scientists. Other ad hoc social science research is also being conducted in the field. Through this proposal we aim to consolidate learning and articulate what is needed to replicate similar initiatives in future outbreaks. We will provide remote technical support, conduct structured critical appraisal of the field experience, capture lessons learned, and develop guidance and tools for the current and for future outbreaks. Our vision is to contribute to better outbreak prevention and response through excellence in social and behavioural science research, integrated into current and future responses to infectious disease threats.",,2021,UNICEF UK,73270.43,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Not applicable,,Filoviridae,,,,,,,,,Ebola virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2020 +P30092,222105/Z/20/A,COVID Kurakani (Covid Conversations): understanding stakeholder perceptions of COVID-19 sequencing in Nepal,"The Wellcome Trust funded Epidemic Intelligence project has implemented large scale genome sequencing for SARS CoV-2 at the only functioning sequencing laboratory in country, and stimulated discussion on the future role of pathogen sequencing and approaches to build capacity in Nepal. COVID Kurakani (Covid Conversations) will engage stakeholders to stimulate increased understanding of the role of pathogen sequencing, allow researchers to listen to, be informed by and respond to community perceptions and concerns around sequencing, build trust between participating communities and the researchers and facilitate capacity building for genome sequencing in the country. Our key goals are: - Build capacity among the epidemic intelligence team to develop and deliver high quality public engagement activities surrounding pathogen sequencing for epidemic response. - Conduct an EDGE analysis of public engagement status at BNMT. - Conduct an internal workshop to design the public engagement strategy, including the senior management team. - Utilise media expertise among the research team to develop and deliver a series of panel discussion programmes for national broadcast with three participatory target audiences. - Understand community and stakeholder perceptions of COVID-19 sequencing. - Address knowledge gaps and concerns among stakeholders to build trust and inform the dialogue surrounding pathogen sequencing.",,2022,Birat Nepal Medical Trust,42612.08,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,Unspecified,,,,Nepal,,"Pathogen: natural history, transmission and diagnostics | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Community engagement | Communication",2022 +P30093,227492/Z/23/Z,The impact of Long Covid in the multi-morbid individual - integration into a multi-morbid exercise-based rehabilitation programme,"Almost half of people have ongoing symptoms following COVID-19 (such as fatigue and feeling short of breath) that may affect their day-to-day lives (Long COVID). Research to date suggests that education and exercise-based rehabilitation may improve symptoms and quality of life for some people living with Long COVID. People living with two or more (multiple) pre-existing long- term conditions (LTCs) (such as Diabetes and Asthma) are more likely to develop Long COVID. But little is known about how Long COVID impacts their health and well-being in particular and how best to support them. The overall aim of the research is to understand the impact of Long COVID on people living with multiple pre-existing long-term conditions, and to contribute to the development of an intervention to improve their health and well-being. - We will review data from an existing study (PHOSP-COVID) to identify the impact of Long COVID post-hospitalisation on health and well-being. - We will review the outcomes of a local rehabilitation programme in addition to all existing studies that have trialled education and exercise-based rehabilitation for people with Long COVID. - We will use interviews to explore experiences of Long COVID, and views on a newly-developed rehabilitation programme for people with multiple LTCs.",,2025,University of Leicester,,Human Populations,Unspecified,Unspecified,Unspecified,Individuals with multimorbidity,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Clinical characterisation and management | Secondary impacts of disease, response & control measures","Supportive care, processes of care and management | Post acute and long term health consequences | Indirect health impacts",2022 +P30094,215858/Z/19/Z,Much Needed Incidence Studies in Support of Lassa Fever Vaccine Development,"An improved understanding of Lassa virus (LASV) seroprevalence and incidence is critical for proper design of LASV vaccine studies in humans. The current understanding of LASV epidemiology and circulating LASV genotypes is limited and based on small studies conducted several decades ago. The lead applicant has significant experience with large-scale epidemiology studies, and the participating investigators maintain a strong presence in Sierra Leone with extensive experience with Lassa field studies, including cross sectional studies and advanced LASV clinical laboratory capacity. The cross-sectional visits and surveillance for Lassa fever cases is conducted by teams of outreach workers, and the overall project team is well-versed in epidemiological survey methods, questionnaire administration, informed consent and collection of blood in community settings. We are seeking Wellcome Trust funding to determine incidence and genotypes of LASV in various hotspots in Sierra Leone to inform rationale vaccine trial design and trial site selection. To this end, we propose enrolling 8,000 volunteers from 40 villages (20 of which have participated in the initial cross sectional study and 20 are new study villages) for two visits to determine LASV incidence. Support for epidemiological research will strengthen our partner sites and develop local investigators' capacity to conduct clinical trials.",,2024,International AIDS Vaccine Initiative,843043,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2020 +P30095,223271/A/21/Z,Leveraging COG-UK expertise to support the global dissemination of SARS-CoV-2 genome sequencing,"Control of the COVID-19 pandemic depends on the development and equitable roll-out of vaccines that remain effective over time. But the evolution of SARS-CoV-2 variants that exhibit variable degrees of immune evasion, and other characteristics including greater transmissibility and/or lethality, threaten to undermine our ability to control COVID-19. It is widely accepted that vaccines will need to be altered over time as the virus mutates. Effective vaccine re-development is dependent upon the availability of global viral sequence data, but there is a lack of sequence data for much of the world, including low, middle and high-income countries. The COVID-19 Genomics UK Consortium (COG-UK) (including the Wellcome Sanger Institute) will leverage its expertise to develop a comprehensive global learning programme on SARS- CoV-2 genome sequencing (COG-GLOBAL). This will be achieved by working with experienced on-line educators. Specific aims include the development of an open access, online modular global learning programme on SARS-CoV-2 sequencing and analysis, allowing users to follow pathways of learning according to professional expertise (laboratory scientist, clinical practitioner, data scientist & epidemiologist, bioinformatician or policy maker); and the development of train-the-trainer courses in collaboration with the Wellcome Connecting Science Advanced Courses, Wellcome Africa and Asia Programmes, and other contributors.",,2023,Wellcome Sanger Institute,658028.15,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Health Systems Research,Health workforce,2021 +P30096,224690/Z/21/Z,"Ready2Respond, a public-private collaborating platform to address pandemic preparedness gaps in low- and middle-income countries - Phase 2 Funding","Following a 2019 meeting of global health leaders with expertise in influenza, vaccinology and pandemic preparedness in London hosted at the Wellcome Trust, Ready2Respond was formed as a global collaboration of partners committed to enhancing low- and middle-income countries' readiness to respond against influenza and respiratory pandemics. With a Secretariat hosted at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza, the organization's plan now includes COVID-19. Under the oversight of a Management Secretariat, Expert Working Groups design and execute cross- collaborative projects organized in 3 strategic pillars: - Burden of Disease - Risk Communication and Community Engagement - Vaccine Access Ready2Respond seeks a grant from the Wellcome Trust of US$ 492,970. This grant will enable Ready2Respond to focus on two initial and critical projects identified in the Burden of Disease pillar. This grant will also allow for retention of paid Director, responsible for ensuring that identified projects represent discrete operational improvement activities for LMICs, and cover part-time staff. Finally, this grant will help secure communication activities aimed at raising awareness and funding from potential partners. This Phase 2 of funding will span September 2021 - February 2022.",,2022,Task Force for Global Health,504317.89,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,Epidemiological studies,Disease surveillance & mapping,2021 +P30097,226729/Z/22/Z,"WHO R&D; Roadmap for Crimean-Congo Haemorrhagic fever: update, launch and stakeholder involvement","As part of the WHO research and product development (R&D) Blueprint initiative for epidemic prone diseases, in 2018 the UK Health Security Agency (UKHSA) partnered with WHO to develop an R&D roadmap for Crimean-Congo Haemorrhagic fever (CCHF). An advanced draft roadmap was produced that prioritised the development of those countermeasures - diagnostics, therapeutics and vaccines for human or animal use - that are most needed by CCHF-affected countries, and set the direction and timelines for future CCHF product R&D activities. Progress was then interrupted by the COVID-19 pandemic. This proposal focuses on updating and launching the WHO R&D Roadmap for CCHF and supporting activities for its dissemination and early adoption. The knowledge landscape since 2018 will be reviewed, the priorities and timelines set in the draft CCHF roadmap revisited and updated and a finalised roadmap delivered to WHO for formal publication on their website. A companion publication will be submitted to an open-access scientific journal. After launch, a stakeholder event will raise awareness of the CCHF roadmap and identify R&D activities planned by stakeholders that align with the roadmap priorities, thus facilitating its early adoption. An additional objective is to update a comprehensive landscape analysis and make this openly available.",,2024,UK Health Security Agency,68530.24,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Bunyaviridae,,,,,,,,,Crimean-Congo haemorrhagic fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience | Health Systems Research",Policy research and interventions | Health leadership and governance,2022 +P30098,226072/Z/22/Z,Climate Sensitive Vector Borne Disease Intervention Tools,"The impact of climate change on mosquito-borne diseases are highly uncertain and will vary regionally as people and mosquitoes adjust in different ways. Estimates of how climate influences mosquitoes' ability to spread disease are scarce, with experiments typically conducted in artificial environments with inbred-laboratory strains. High-quality entomological data from disease endemic areas will be essential to produce meaningful future projections. This project proposes to develop a flexible user-friendly interface to allow policymakers, stakeholders and researchers to explore the epidemiological consequences of the changing environment. The tool will empower primary data collection by translating user defined estimates of how mosquito bionomics may change over time into disease projections in their local environment given existing and future control interventions. Users can also input projections of disease burden from statistical models and investigate the public health measures needed to mitigate the effects of climate change. The project will focus on malaria and the arboviruses dengue, zika and chikungunya. It will build on the existing malaria interface (https://mint.dide.ic.ac.uk/) to include climate sensitive mosquito bionomics inside established disease- specific mechanistic models. Situations ranging from disease introduction to increasing mosquito abundance will be explored to allow future scenario planning including economic evaluations across spatial scales.",,2027,Imperial College London,601550.06,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Environmental stability of pathogen | Vector control strategies,2022 +P30099,225128/Z/22/Z,Investigating the Role of Neuropilins in Facilitating Pan-Viral Infections,"Viruses gain access to host cells through the specific recognition of biomolecules at the cell surface. My research focuses on neuropilins, a family of host-encoded surface receptors that recognise multibasic C-terminal motifs in circulating extracellular ligands. I recently demonstrated that the Spike glycoprotein of the pandemic coronavirus SARS-CoV-2 exhibits molecular mimicry to generate a sequence capable of binding to Neuropilin-1, thereby enhancing infection of human cells. Bioinformatic analysis suggests that a broad range of additional viral glycoproteins also generate putative neuropilin-binding motifs, including high-profile pathogens such as MERS-CoV, Influenza A virus, Ebolavirus and HIV-1. I will establish infection screens, utilising pseudotyped lentiviruses and authentic live viruses where appropriate, to directly test the role of neuropilins in facilitating infection of human cells by these pathogens. Through a network of collaborations, I will screen small molecule compounds to identify inhibitors of this infection process. This approach will be supported by biochemical characterisation of the molecular interfaces between viral glycoproteins and neuropilins, and investigation of the cell biological pathways that underpin this infection mechanism. Together, this interdisciplinary approach aims to clarify the role of neuropilins as ""pan-viral"" therapeutic targets and potentially inform the development of antiviral compounds for the treatment of infectious diseases.",,2027,King's College London,513763.86,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Filoviridae | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Ebola virus disease | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Therapeutics research, development and implementation","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Pre-clinical studies",2022 +P30100,228319/Z/23/Z,The impact of background genetic diversity in inferences of SARS-CoV-2 transmission and selection,"The virus SARS-CoV-2 is the cause of the COVID-19 pandemic. At any point during the pandemic, there is a range of SARS-CoV-2 viruses with different mutations spreading: the background diversity. I will use the Office for National Statistics' COVID-19 infection Survey (ONS-CIS) genomic data to examine how changing levels of background diversity affects the methods we use to infer transmission when we have two linked sequences; to do this I will focus on using phylogenetics (tree-based methods). For example, if the background diversity is high, we have more confidence that two sequences from the same household that are highly similar represent a transmission event, compared to the same two sequences against a low diversity background. Additionally, I will examine methods for determining whether two sequences from the same individual represent a persistent infection or reinfection, taking into account changing background diversity. Finally, I aim to investigate selection, examining whether conflicts occur in which a mutation provides an advantage during infection (within-host) host but becomes disadvantageous during transmission (between host). This project will allow us to examine current methods and evaluate their suitability at different background diversity levels, and will have implications for the optimal use of genomics in other infections.",,2026,University of Oxford,,Human Populations | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2023 +P30101,228339/Z/23/Z,Genomic Signatures of SARS-CoV-2 Superspreading Associated with Large Events: Unravelling Transmission Dynamics in Scotland,"SARS-CoV-2 affects areas with high poverty more severely, and the rate and extent of its transmission varies in different settings. Events like the 2021 European Football Championships (EURO 2020) and COP26 were considered high- risk for spreading the virus. Despite their social and global significance, many debated stricter restrictions on these events during the pandemic. The surge in cases in participating countries was linked to gatherings associated with the EURO 2020. My research focuses on understanding the risks of large gatherings, to ascertain how these events influenced the patterns of SARS- CoV-2 transmission, and whether greater restrictions would have been merited. To explore this, I'm using a network-based model that blends various types of data, including exceptional genetic information from the virus. I'll also explore how wealth and location impact transmission among different socioeconomic groups. The goal is to identify patterns that explain why certain events and socioeconomic groups become hotspots for virus transmission. Understanding these dynamics will help us tailor public health strategies regarding these events more effectively. This could be invaluable for managing future outbreaks of COVID-19 or similar viruses.",,2026,University of Edinburgh,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease susceptibility,2023 +P30102,225227/Z/22/Z,"Multi-layered medical uncertainty: The interaction between medical research, the clinic and patient experience in the context of highly uncertain conditions","How can we understand the different forms of medical uncertainty, their interplay, the debates that surround them and the linkages with socio-economic vulnerability? Using qualitative in-depth interviews with patients, clinicians and researchers, documentary analyses and hashtag ethnography, this project will explore four conditions characterised by multi-layered medical uncertainty (i.e. simultaneous uncertainty about aetiology and diagnosis alongside the scarcity of specific treatments) both in their historical developments and in everyday experiences. The four conditions that will be explored are fibromyalgia, ME/CFS, Long Covid and chemobrain. The project will explore how patients contend with the illness experience, the often difficult processes of obtaining a diagnosis and having it recognised by other medical professionals and society at large, and the scarcity of specific treatments. The project will further analyse how clinicians and researchers manage the everyday uncertainty in their work, and the debates, negotiations and conflict between them and the patients surrounding the definitions of these conditions. The result will be an understanding of medical uncertainty that is multi- dimensional, dynamic and social. Finally, this project will include a public engagement component that aims to increase awareness of these conditions and of their under-diagnosis and under-recognition, particularly among primary care professionals.",,2028,University of Manchester,666238.49,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Physicians,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Clinical characterisation and management | Policies for public health, disease control & community resilience",Post acute and long term health consequences | Community engagement,2023 +P30103,227507/Z/23/Z,Mechanism and biological importance of neutralising antibodies against SARS- CoV-2,"Getting infected or being vaccinated against the SARS CoV-2 virus causes the immune system to make 'neutralising' antibodies, which block infection and stop people becoming unwell. Nonetheless, it is still not known what level of these antibodies is required for protection, or exactly how they work. We have previously discovered that SARS-CoV-2 can spread directly between cells (cell- to-cell spread), as well as by releasing virus particles into the surroundings (cell-free infection). We have also shown that antibodies targeting separate parts of the virus can preferentially block one or other of these types of infection. In this project, I will therefore measure the levels of antibodies blocking different types of infection in blood samples from patients and healthy volunteers, and compare them with rates of infection and severe disease. I will further use 'CRISPR' gene editing technology to investigate how the virus spreads between cells. Altogether, this will allow me to determine what levels of antibodies are required for protection against SARS- CoV-2, and how important the different types of antibody are. It may also uncover factors in cells which can be targeted by new therapies to stop the virus spreading and prevent COVID-19.",,2025,University of Cambridge,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +P30104,224676/Z/21/Z,Informing models of Influenza antigenicity using structural biology,"Influenza viruses cause hundreds of thousands of deaths each year. Despite a long-standing awareness of 'flu' in the research community, leading to the availability of vaccines for almost 70 years, it still presents a very real concern for public health. This is largely due to the fact that influenza viruses undergo a process known as antigenic drift. This allows the virus to sidestep immune responses that have been formed in individuals who have been exposed to the virus in the past or who have been vaccinated against influenza, by acquiring mutations in the surface protein haemagglutinin. By using electron microscopy to solve the structure of many haemagglutinin molecules from diverse strains of influenza and leveraging protein structure data from previous studies, we plan to construct computer models of the changes in this key protein which allow it to evade immune responses. These models will help vaccine designers and public health officials to anticipate trends in the spread of different flu strains and prevent deaths from flu by designing more effective vaccines faster.",,2024,University of Glasgow,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Unspecified,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P30105,217924/Z/19/Z,Investigating the Impact of the International Response to the 2014 West African Ebola Crisis,"The 2014 West African Ebola crisis was the deadliest outbreak in this region. While the international response was delayed, eventually international actors, including scientists, clinicians, NGOs, and governments came to the aid of affected countries. What remains unclear is the impact of the international response on key African actors and institutions. This project will investigate the impact of the international response on the visibility, agency and capacity of African scientists, researchers and other key stakeholders. Through a social network analysis, using authorship and institutional affiliations, this project will map scholars contributing to the global discourse on Ebola. Additionally, a scoping review will be used to determine how the crisis of Ebola was framed. Combined, they may suggest the relative power African scientists had in shaping the scientific dialogue around this epidemic. This project will also conduct interviews with key stakeholders such as scientists, researchers, and policy makers in Nigeria, Sierra Leone and Liberia. Regional actors based at Africa CDC, will also be included. These interviews will provide important perspectives from key African actors about how the international response to the Ebola crisis, impacted on their agency, capacity and visibility during and after the crisis.",,2024,University of Cape Town,173441.99,Human Populations | Other,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Policy research and interventions | Other secondary impacts,2020 +P30107,226141/B/22/Z,G2P - Global Knowledge Exchange to Enable In Country Risk Assessment of SARS CoV-2 Variants,"SARS CoV-2 continues to evolve. Novel variants are driven by high levels of global transmission and viral replication, sustained selection pressures imparted by existing immunity acquired through natural infection and vaccination, and increasing use of antivirals. Building on G2P-UK, established working partnerships between teams in the UK, Africa and India, and an ethos of free knowledge exchange, we outline 4 inter-related aims that will enable and prepare G2P-Global to evaluate the significance of emerging viral variation across 3 continents. We will: 1) Implement standardized methodologies that enable rapid in-country risk assessment of the biological and antigenic properties of SARS-CoV-2 variants of concern (VOCs), providing real-time data for guiding infection control and vaccination policies; 2) Undertake discovery-led molecular, cellular and in vivo (hamster) analyses of variant phenotypes to address the mechanistic basis for how the virus can evolve while balancing immune escape with the maintenance of efficient respiratory transmission; 3) Assess the potential for spill-overs into domesticated and wild animal species and subsequent reservoir seeding; 4) Establish communications networks and laboratory resources that will build technical and logistical preparedness enabling G2P-Global partners and additional collaborators to undertake in-country virological assessments of future respiratory virus outbreaks, and associated virus variants.",,2026,CBCI Society for Medical Education,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,Unspecified,,,,India,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities",2023 +P30108,219798/Z/19/Z,Understanding the contribution of influenza vaccines to antibiotic prescribing in the UK population.,"Vaccination should reduce antibioticl prescribing (AP), the driver of antimicrobial resistance. Looking for reductions in Randomised Controlled Trials of vaccine is problematic as they are usually powered for large effect sizes of specific end-points. An alternative approach is to undertake observational studies using large routine data sources. The problem with this approach is ensuring major confounding is identified and accounted for when linking vaccine status and outcome and, demonstrating a causal relationship. We will conduct an observational study using the Clinical Practice Research Datalink (2007-2019) and The Health Improvement Network (THIN) (2007-2019) from the United Kingdom. Our primary aim is to measure AM prescribing in adults over 65 and children under 5 by frequency of influenza vaccination. We will use three complimentary approaches and different methods to adjust for confounding: 1 A Self-controlled case series - comparing annual AM prescribing within individuals by annual receipt of influenza vaccine and vaccine/pathogen match. 2 A Cohort study - balancing comparator populations using propensity scoring to control for major determinants of health care utilisation and underlying health status. 3 An Interrupted time series analyses - investigating paediatric influenza vaccine uptake (September 2013) and AM prescribing",,2024,University of Liverpool,335863.8,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Epidemiological studies | Vaccines research, development and implementation",Impact/ effectiveness of control measures,2021 +P30109,226809/Z/22/Z,Structural Studies of Influenza Virus Restriction Factors,"Influenza viruses cause seasonal epidemics and occasional pandemics which pose a significant burden to public health and the global economy. Influenza viruses are segmented, negative-sense RNA viruses, meaning that each infectious viral particle must contain eight viral ribonucleoprotein (vRNP) complexes - containing viral RNA wrapped around nucleoprotein monomers bound to the influenza polymerase complex. This core unit is responsible for efficient genomic packaging and viral replication. Various human proteins (host factors) are required for viral replication, or else are key in the host antiviral immune response. However, detailed mechanistic and structural insights are lacking. Of particular interest is the interaction between vRNPs and Human Myxovirus Resistance Protein 1 (MxA) - a host factor known to restrict the replication of certain influenza virus strains. Primarily using specialised electron microscopy techniques, I will examine: - The structural basis of MxA-mediated restriction of influenza virus in the innate host immune response - How key mutations in certain strains of influenza can lead to humans becoming more susceptible to infection Improved understanding of the influenza lifecycle and of the involvement of host factors in the immune response will be useful to inform future structure-based drug design in the pursuit of specific inhibitors of influenza virus replication.",,2025,University of Oxford,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P30111,226832/Z/22/Z,Developing tools for outbreak response: from lineage assignment to epidemiological impact,"Over the course of the COVID-19 pandemic, increasing amounts of genomic data from the SARS-CoV-2 have become available to researchers and public health officials around the world. Analysing the genetic code of virus samples allows researchers to classify them and track how they spread. My project will focus on developing tools for classifying viruses and tracking their spread. A good classification tool should be able to sort virus samples quickly and accurately. As part of the project, I will design and test a tool for classifying SARS-CoV-2 viruses, aiming to create a tool that is faster and more accurate than existing tools. I will then aim to extend this to other viruses. This will involve a computational-based approach, using publicly- available virus sequences to test the performance of the tool. The tools developed as part of the project will have impact in a scientific and public health context. Accurately sorting viruses allows researchers and public health officials to track their spread, monitor new variants and understand their evolution. My project aims to build a tool that will assist in these objectives, while producing insights into viral evolution.",,2025,University of Edinburgh,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,Innovation,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P30112,224494/A/21/Z,Long-term consequences of Zika virus infections during pregnancy for school- aged children and their families in Brazil,"Using unparalleled epidemiological, administrative, and social science data continuously collected from 2015 onwards in Brazil, this collaborative proposal aims to define the prognosis and learning needs of school-aged children with prenatal exposure to Zika virus (ZIKV) and the long-term health and social impacts for families of children with Congenital Zika Syndrome (CZS). Through four linked work packages, we will: (i) define the natural history of CZS in the first 12 years of life, including the frequency of late- onset manifestations, hospitalizations, and deaths, (ii) compare neurodevelopment and learning-related outcomes in children with and without CZS, (iii) evaluate long-term consequences of CZS for families, including implications of COVID-19, and (iv) critically interrogate the experience of families engaging in research and data sharing initiatives during and after public health emergencies. To achieve these aims, we are requesting resources to perform comprehensive clinical and neurodevelopmental assessments in the Microcephaly Epidemic Research Group and ZIKAIFF Pediatric Cohorts in Pernambuco and Rio de Janeiro states, undertake a nationwide individual participant data meta-analysis of ZIKV-related clinical and neurodevelopmental outcomes among children in the Zika Brazilian Cohorts Consortium, link large- scale nationwide electronic health and social records in the CIDACS/Fiocruz Zika Platform, and conduct qualitative research with key stakeholders.",,2029,The Foundation for Scientific and Technological Development in Health,1739749.65,Human Populations,Unspecified,Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease | Congenital Zika virus disease,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,Brazil,,"Epidemiological studies | Clinical characterisation and management | Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Disease pathogenesis | Post acute and long term health consequences | Policy research and interventions | Indirect health impacts,2022 +P30113,223705/Z/21/A,Public Engagement to strengthen COVID-19 genomics research in Africa,"This proposal aims to engage key audiences in Ghana such as SARS-CoV-2 Genomic Surveillance researchers, university students, high school students, media professionals, and animators to guide the development and use of animation toolkits for aiding public engagement with SARS-CoV-2 Genomic Surveillance, create three animations on SARS-CoV-2 genomic surveillance, and train researchers and media professionals to use the toolkits to engage key audiences including university and high school students, and other members of the public. The animations will focus on issues including how viruses mutate, use of sequencing to detect variants, and how variants affect COVID-19 evolution. We will assess toolkits' impacts using surveys and focus group discussions with priority audiences, including researchers and media professionals who will use the toolkits. We will use the findings to develop best practice for implementing and evaluating public engagement with genomic surveillance. To build capacity in public engagement with genomic surveillance, we will use a) train-the-trainer approach, and b) focus group discussions, key informant interviews and a deliberative workshop with genomic researchers and media professionals to create two research strategies: one focusing on how researchers could engage with members of the public, and a second focusing on researchers-media professionals' engagement with genomic surveillance.",,2024,University of Cambridge,140234.3,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Community engagement | Policy research and interventions,2022 +P30114,226066/Z/22/Z,Funding for CEPI 2.0's next five-year business cycle 2022-2027,"CEPI's 2022-2027 strategic priorities are founded on the three pillars of Prepare, Transform and Connect. CEPI will prepare for known epidemics and pandemic threats by developing vaccines and promising biologics against the most prominent known threats, building on COVID-19 achievements and CEPI 1.0. CEPI will transform the response to the next novel threat by harnessing innovations in technology and systems to significantly reduce the global vulnerability to threats from novel pathogen outbreaks. CEPI will enhance and expand global collaboration by connecting emerging infectious disease stakeholders to enable rapid countermeasure development, effective response and equitable access for those in need. If the products developed with CEPI's funding are to realise their potential, they should flow through a system with pre-agreed governance, financing, allocation, and distribution mechanisms to govern their ultimate use. CEPI is already contributing to and helping shape a post-pandemic consensus, creating a well-prepared ecosystem able to react quickly without leaving anyone behind.",,2028,Coalition for Epidemic Preparedness Innovations (CEPI),134241291.6,Not applicable,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Novel Pathogen,,,,,,,,,Disease X,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Norway,,Health Systems Research,"Medicines, vaccines & other technologies | Health leadership and governance",2023 +P30115,225288/Z/22/Z,The ISARIC data platform: Optimizing data-driven pandemic preparedness and response,"Taking the lessons learned from the international success of ISARIC's COVID-19 data platform, we will expand the platform to answer new questions on COVID-19 and build data systems to respond to future outbreaks of infectious diseases. This collaboration brings together scientists who have developed world-leading data integration, processing and analytic technologies with health care workers and public health specialists who will use and tailor the technologies to deliver evidence that's relevant to patient care and public health policy decisions. Together we will expand the data platform to 1) integrate epidemiological and clinical data so that we can analyse research questions at an individual level and a population level; 2) integrate genomic data so that we can understand how different virus variants affect patient outcomes; and 3) provide the infrastructure to scale data processing and grow our international network to generate more evidence on emerging infectious diseases. We will analyse these integrated data sets to generate evidence on the impact of vaccination and new variants in COVID-19 infection and post-acute COVID-19 syndrome. We will also develop methods to accelerate science on the characterisation of future disease outbreaks.",,2024,University of Oxford,1323398.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical | Non-Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Impact/ effectiveness of control measures | Supportive care, processes of care and management | Post acute and long term health consequences | Characterisation of vaccine-induced immunity",2022 +P30116,222305/Z/21/A,Defining the Protective Immune Response to SARS CoV2 Using a Human Challenge Model,"Understanding the nature, effectiveness and durability of the human immune response to SARS CoV2 is crucial for vaccine development and effective public health management. We are beginning to understand the pattern and kinetics of the humoral response to natural infection but are less certain about other aspects of the response. We are unable to establish with certainty whether an individual with a particular titre of antibody, or a particular T cell response, is likely to be protected from reinfection and, if so, for how long. These are central questions for the development of an effective vaccine. A controlled human infection model will provide a more detailed understanding of the protective immune response. It will provide the opportunity to interrogate the full extent of the immune response at the time of exposure and will also allow the evaluation of the durability of immune responses of all kinds and how they correlate with protection. Key goals: - To establish an MHRA-approved SARS CoV2 viral stock for use in a controlled human infection model - To determine a challenge dose which is safe and allows virus to be recoverable from infected subjects",,2023,University of Oxford,2515307.26,Human Populations | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P30117,227483/Z/23/Z,Exploring the Therapeutic Relationship in modern General Practice,"Plain English summary (350 words maximum): Background: The relationship between patient and doctor has long been an important part of medicine and has been historically celebrated for its richness, humanity and therapeutic potential. High-quality relationships can lead to greater patient and professional satisfaction, compliance and efficiency, whilst continuity is associated with improved health outcomes. However, recent years have seen considerable changes in Primary care, accelerated by the Covid-19 pandemic, including remote approaches and a more diverse workforce. Approach: I will explore the effect of these changes on the therapeutic relationship between patients and their primary care teams. I will select 10 patients from 3 diverse GP practices and will follow them for 2 years, using a range of qualitative and ethnographic methodologies to analyse their interactions with their GP and the wider practice systems. Impact: This will inform training programmes for medical students and GP trainees and academic papers and policy documents for health care providers and commissioners. I aim to provide insights about how training, technology or workstreams can be optimized for primary care to contribute to therapeutic encounters that improve health outcomes and result in greater patient and professional wellbeing, and more efficient systems.",,2027,University of Oxford,,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Physicians | Other,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2022 +P30118,220991/Z/20/Z,Investigation of pre-existing immunity to coronaviruses; implications for immunopathology and pathophysiology of COVID-19 disease,"Background; It is unknown how prior exposure to commonly circulating human coronaviruses (HCoV) impacts immunity against highly-pathogenic species (SARS, SARS-CoV-2 & MERS). There are limited data, across Europe, Asia and Africa, on the prevalence of infection and seroconversion against widely circulating and mildly symptomatic HCoVs (229E, NL63, OC43, and HKU1). There is a current supposition that antibody-dependent-enhancement (ADE) may play a role in the pathophysiology of COVID-19. ADE occurs when non-neutralizing antiviral proteins facilitate virus entry into host cells, leading to increased infectivity in the cells. In such cases, higher viremia has been measured and the clinical course of disease can be more severe. In preclinical animal models, immunopathology was observed after challenge following vaccination with some SARS vaccines. Therefore, concerns have been raised regarding the impact of immunopathology and ADE on prophylactic vaccination against SARS and possibly SARS-CoV-2. Goals: to perform detailed systems serology of pre- existing immunity, in children and adults, from the UK and Africa, towards novel and commonly circulating coronaviruses. Impact: These studies highlight the limited knowledge in the field and a need for a systematic approach to investigate cross-reactive humoral immunity against HCoV to inform the immunopathology and pathophysiology of COVID-19.",,2023,University of Oxford,935687.39,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Severe Acute Respiratory Syndrome (SARS),Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2020 +P30119,203160/A/16/Z,Conducting Ethical Research With Pregnant Women in the Emerging Zika Pandemic and Beyond: Challenges Arising in Public Health Crises,"The central research question of the proposed project is how, in the context of the Zika crisis, to address the myriad ethical challenges that arise in the conduct of research when there is an urgent need to attend to the health needs of pregnant women and their offspring. An essential and integrated sub- question is to examine these same challenges in the context of public health emergencies more generally, to avoid repeating mistakes from the past and anticipate future public health needs. The core objectives of the project are: 1. To conduct engagement with key experts, and conduct scholarly research in ethics and law, in order to understand the needs, challenges, and opportunities for conducting research on pregnant women and women who may become pregnant 1 in the Zika context, in particular, and public health emergencies, in general; 2. To develop, in conjunction with an international expert advisory group, rapid and ongoing concrete ethical guidance for conducting research involving pregnant women in the Zika context, and a framework for approaching public health emergencies requiring research in pregnant women. Using the methods described below, Year 1 will emphasize the most immediate and time-sensitive issues for advancing Zika research for pregnant women. Year 2 will provide ongoing analysis and guidance as the Zika crisis evolves and research findings emerge, and will further develop analysis and guidance on research involving pregnant women in public health emergencies more broadly, including research specific to other potential infectious disease outbreaks and to environmental and bioweapons threats.",,2020,Johns Hopkins University,,Human Populations,Unspecified,Unspecified,Unspecified,Pregnant women,Unspecified,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,"Policies for public health, disease control & community resilience | Research to inform ethical issues",Community engagement | Research to inform ethical issues in Research,2020 +P30120,221539/Z/20/Z,LASCOPE extension,"The ""Lassa fever Clinical Course and Prognostic factors (LASCOPE)"" project is a prospective cohort study of patients with acute symptomatic Lassa fever (LF) hospitalized in dedicated treatment centers in Nigeria. The patients have access, free of charge, to reliable molecular diagnosis of LF, ribavirin therapy and an improved standard of supportive care including renal replacement therapy. This study aims at producing up to date data on LF disease presentation and course, management, outcomes and factors associated to fatality. The data produced by the LASCOPE study will inform the design of future trials evaluating innovative therapeutic strategies for LF, as well as the development of updated guidelines for the management of patients with LF. Lastly, this project will contribute to the development of clinical research capacities in the participating sites and put them in position to conduct future therapeutic and vaccine trials for LF.",,2020,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Clinical characterisation and management,"Supportive care, processes of care and management | Disease pathogenesis",2020 +P30121,226107/Z/22/Z,A model-driven software development platform for Climate-Sensitive Infectious Disease Modelling,"The COVID-19 pandemic demonstrated the value of epidemiological models in battling against the disease. However, modelling is not a trivial task. It requires time, effort and continuous maintenance to address the evolution of the disease and of the countermeasures. On one hand, this requires a systematic and robust development process to ensure the effectiveness and the quality of the produced models. On the other hand, it also implies the need for a change management process that will handle the maintenance and the evolution of the models. Furthermore, infectious diseases have to be studied in conjunction with other affecting parameters, include climate and sociodemographics. Therefore, modellers need to be able to consider multidimensional and hybrid models to better study the phenomenon. In this project, we propose the application of software engineering and model-driven engineering principles to aid the design, development and simulation of climate-sensitive infectious disease models. More specifically, we propose a integrated development platform that will support (a) the definition and design of models, (b) the simulation of scenarios based on these models, (c) the automatic validation and verification of models and code generation, (d) the control of model versions, and (e) the merging of models from different domains.",,2028,York University (Canada),331118.97,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,Canada,,Epidemiological studies,,2023 +P30123,226817/Z/22/Z,Wellcome Centre for Infectious Diseases Research in Africa Discovery Platforms in Science,"The Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) fosters investigator-led approaches via the overarching scientific objective of combatting infection, especially HIV-1, tuberculosis (TB) and lower respiratory infections including COVID-19. The centre is already organised into three platforms supporting Clinical Science, Basic Science and Data integration. This application will strategically build on, and sustain, the success of these platforms by providing skilled human and state-of-the-art technical resources. Specifically 1. The clinical platform will strengthen capacity to investigate more rational use of existing, repurposed and new anti-infectives and vaccines by supporting its facilities to provide imaging, regulatory compliance, data capture and analysis and on site laboratory capability. In particular the pharmacokinetic and pharmacodynamic (PK/PD) analyses will be improved by appointment of senior nurse dedicated to PK/PD studies and by the part-time appointment of a pharmacometrician. 2. The Basic Science will expand access and training in existing world-class imaging facilities to provide project specific solutions and expertise to projects that require single cell technologies. 3. The Data integration platform will increase availability of end-to-end bioinformatic services and also increase the ability of researchers to harness the Public Health Data Centre: a continentally unique single consolidated environment for person-level health data.",,2031,University of Cape Town,11750862.93,Not applicable,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,"Therapeutics research, development and implementation | Vaccines research, development and implementation",Pre-clinical studies | Prophylactic use of treatments,2024 +P30124,225437/Z/22/Z,Affordable and scalable remote monitoring platforms for disease characterisation and patient management in pandemics and for high-consequence infections,"Characterising new and emerging life-threatening infectious diseases safely, and optimising clinical management strategies, are essential early activities in an epidemic/pandemic response. New technologies, wearable devices, cloud computing, and machine learning (ML), offer potentially transformative solutions. Vietnam has just experienced its first major COVID-19 wave. Cases are rising again. In wave one, a shortage of monitoring equipment caused serious delays in identifying and treating those with severe disease. Conventional remote-monitoring systems, needed for safe monitoring, cost upwards of £12,000 for a single patient which is unfeasible in Vietnam. Our objective therefore is to provide proof-of principle that a team within Vietnam can establish a low-cost remote monitoring platform during a pandemic that will aid clinical care and capture data for disease characterisation and research. Our multidisciplinary team in Ho Chi Minh city will develop the platform from a prototype implemented in 50 patients during wave one. The new platform will provide real-time continuous remote monitoring of oxygen saturations and heart rate in 150 patients. We will integrate device, clinical, and laboratory data, and develop a prototype ML-based clinical decision support system for COVID-19. The platform is designed to be rapidly deployable in other low-resource settings and for other emerging infectious diseases.",,2023,University of Oxford,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Clinical characterisation and management,"Supportive care, processes of care and management",2022 +P30125,223547/Z/21/Z,Genomic Surveillance program for SARS-CoV-2: Consortium of India and Sri Lanka,"The global challenges posed by COVID-19 are best tackled through global cooperation between researchers, clinicians and funding agencies. One such challenge is generating timely, high-resolution monitoring of the SARS-CoV-2 viral evolution and using such data to guide public health response in a timely manner. The discovery of current variants of concern (VOC) in UK, South Africa and Brazil is because of a high quality sequencing program (UK) or vaccination related investigations (South Africa, Brazil). Indian SARS-CoV-2 Genomic Consortia (INSACOG) is revealing the possibility of local VOC driving fresh outbreaks. We proposes a network of satellite genomic sequencing MicroLabs in India, Bangladesh and Sri Lanka that will be integrated by virtual cloud-based workflows as well as physical linkages to national MegaLabs for quality assurance and operational support. This would help scale up global monitoring of emerging SARS-CoV-2 strains in one of the world's most populous region and guide global R&D efforts for COVID-19 diagnostics, vaccines and therapeutics. Given the relevance of SARS-CoV-2 surveillance to especially the diagnostics and health systems pillars of WHO's ACT- Accelerator, partners such as Wellcome Trust can play an important role in furthering this effort. There is an urgent need to create distributed local capacity via MicroLab hubs.",,2024,CSIR- Institute of Genomics and Integrative Biology,1776824.35,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,South-East Asia,Unspecified,,,,India,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2022 +P30127,222894/Z/21/Z,Investigation of immune pathways and genetics underlying resistance and tolerance in severe infection,"Infection is very common, but rarely deadly. For my PhD I want to explore the balance between 'resistance' to infection - the ability to kill and destroy invading pathogens like bacteria, fungi and viruses, with 'tolerance' to infection - the ability to bear an infection without adverse effects when these pathogens attack. Both these strategies are governed by immune pathways and are critical to survival from infection. I will focus on whether we can use large human studies, model or in vitro work about the activity of genes when we do get infected and attempt to identify specific pathways that are a 'trade-off' between these two evolutionary strategies - tolerance and resistance . I will target my investigation on the haem degradation pathway, which controls iron transport and storage. Iron is a critical nutrient for both hosts and pathogens, and has been shown to be important in determining infection outcomes. I will explore how this pathway is regulated in large datasets from sepsis and COVID-19 patients. I will also explore the balance between incidence and case fatality of infection using large genetic datasets, to explore whether genes that make you resist infection are more likely to make you die.",,2023,University of Bristol,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Clinical characterisation and management,Disease pathogenesis,2020 +P30128,226137/Z/22/Z,Adaptive responses to SARS-CoV-2 variants in the context of hybrid immunity and immune impairment,"SARS-CoV-2 evolved variants that could escape previous immunity and transmit better. This process so far culminated in the Omicron variant, which led to a global infection wave of unprecedented scale. To ensure an effective response to variants, their biology, evolution, and mechanisms of escape must be better understood. It is critical to rapidly determine cross-protection afforded by vaccination or previous infections against emerging variants and understand the mechanisms for that protection or lack thereof. This will require understanding B and T cell targets, as well as how these relate to emerging variation, to quickly model/predict new viral escape mutations. Such a high- resolution response is only possible by combining immunology, virology, T and B cell biology, antibody mapping, and structural biology, and will need to be done for increasingly hybrid-induced immunity. The effort must also benefit young investigators. Specific Aims 1. Perform immunological surveillance of current and emerging variants and predict future mutations which impact antibody and T cell immunity 2. Determine how increasingly complex hybrid immunity functions against current and emerging variants 3. Determine how immune impairment mediated by co-infection with HIV modulates response to variants 4. Promote the next generation of African scientists through cutting- edge research and scientific exchange",,2025,Africa Health Research Institute,3852733.63,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,South Africa,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations | Immunity",2023 +P30130,218310/Z/19/Z,Advancing flow cytometry for the on-site study of tropical infectious diseases,"We will purchase a FACS ARIA III (BD Biosciences) 4 laser flow cytometry cell sorter, with the capacity to sort cells in bulk and single cells in plates. The flexible system allows us to configure the sorter for our current needs, but can be easily expanded to future requirements, making it an ideal long- term investment. The ARIA III will be placed and maintained in the Immunology Unit, which is situated in a BSLII laboratory, and is accessible for all Institut Pasteur research Cambodia staff. In addition, through collaborations, the cell sorter will be available for all biomedical researchers in Cambodia outside of Institut Pasteur Cambodia. A dedicated and trained research engineer will operate the machine. This equipment will allow us to investigate complex pathogen-host interactions to the single cell level directly on site in a low/middle income country. A flow cytometry cell sorter is indispensable for projects such as the investigation of antibody responses to dengue virus, the understanding the mechanisms of P. vivax receptor-ligand interactions involved in reticulocyte invasion, and the monitoring of vaccine responses to avian and seasonal influenza and rabies virus.",,2025,Institut Pasteur Cambodia,321835.97,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Orthomyxoviridae,Other | Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Western Pacific,Unspecified,,,,Cambodia,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2020 +P30131,225160/Z/22/Z,"Implementation of the Influenza Vaccines Roadmap - Proposal for Monitoring, Evaluation and Adjustment","Improved influenza vaccines are urgently needed to reduce the global burden of seasonal influenza and enable an effective public health response to the ongoing pandemic threat from emerging influenza viruses. The Influenza Vaccines R&D Roadmap (IVR), completed in September 2021 following an extensive global stakeholder engagement process, provides a framework for guiding R&D activities aimed at accelerating the development of improved seasonal influenza vaccines and broadly protective or universal influenza vaccines. To ensure successful implementation of the roadmap's strategies, follow-up activities are needed to promote awareness, encourage stakeholder buy-in, and track outcomes. CIDRAP proposes to conduct a 3-year project to: (1) monitor and evaluate progress in achieving the IVR goals and milestones, including changes in the status of knowledge gaps and barriers to influenza vaccine R&D; (2) revise and update the roadmap to reflect R&D progress, changes in timelines, new knowledge gaps and barriers to influenza vaccine R&D, and learnings from the ongoing development of COVID-19 vaccines; and (3) maintain and update the IVR website as a communications hub for the influenza vaccine R&D community to strengthen engagement and share information and new developments.",,2025,University of Minnesota,1867535.65,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Americas,Unspecified,,,,United States of America,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Communication | Policy research and interventions,2022 +P30132,227559/Z/23/Z,Mechanisms and evolution of innate immune signalling activation across species,"Host species vary markedly in their susceptibility to infection (e.g. for COVID-19, malaria, or tuberculosis). Variability in disease outcome is driven by differential induction of the immune system, especially for inflammatory diseases like COVID-19. This process depends on adaptive immunity, but also critically innate immunity: a conserved defence system built of recognition, signalling, and effector molecules. Immune genes evolve especially rapidly compared to the rest of the genome. However, little is known how immune evolution affects gene expression across species: we have yet to tie immune evolution to observable differences in the induced response. My research shows closely-related species can differ markedly in their induced immune response. Using a comparative approach, I will systematically characterise immune induction patterns of diverse species. Differences should rely on either i) alternate organisation of conserved immune pathways, or ii) gene duplications that evolve to promote novel pathway connections. Assessing gene expression, molecular evolution, and signalling organisation will reveal how these variables produce differences in immune activation. Ultimately, I will tie immune evolution to differences in the induced immune response. This proposal will greatly improve our ability to predict interactions between pathogens and novel host species, and to understand factors affecting the innate inflammatory response.",,2029,University of Exeter,990376.78,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19 | Unspecified,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2024 +P30133,220977/Z/20/Z,African COVID-19 Preparedness (AFRICO19),"Our project, AFRICO19, will enhance capacity to understand SARS-CoV-2/hCoV-19 infection in three regions of Africa and globally. Building on existing infrastructures and collaborations we will create a network to share knowledge on next generation sequencing (NGS), including Oxford Nanopore Technology (MinION), coronavirus biology and COVID-19 disease control. Our consortium links three African sites combined with genomics and informatics support from the University of Glasgow to achieve the following key goals: 1. Support East and West African capacities for rapid diagnosis and sequencing of SARS-CoV-2 to help with contact tracing and quarantine measures. Novel diagnostic tools optimized for this virus will be deployed. An African COVID-19 case definition will be refined using machine learning for identification of SARS-CoV-2 infections. 2. Surveillance of SARS-CoV-2 will be performed in one cohort at each African site. This will use established cohorts to ensure that sampling begins quickly. A sampling plan optimized to detect initial moderate and severe cases followed by household contact tracing will be employed to obtain both mild to severe COVID-19 cases. 3. Provide improved understanding of SARS- CoV-2 biology/evolution using machine learning and novel bioinformatics analyses. Our results will be shared via a real-time analysis platform using the newly developed CoV-GLUE resource.",,2023,London School of Hygiene & Tropical Medicine,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Diagnostics | Pathogen morphology, shedding & natural history | Disease susceptibility",2020 +P30134,225230/Z/22/Z,MOVING BEYOND SOLIDARITY RHETORIC IN GLOBAL HEALTH: PLURIVERSALITY AND ACTIONABLE TOOLS,"Solidarity is an often-invoked concept in global health. Appeals to solidarity at national and international levels have multiplied in the wake of the Covid-19 pandemic. Yet, at the international level, the results have failed to ensure equity in the production and allocation of resources for combating and mitigating the devastating effects of the virus. Historically, solidarity has proven to be an efficient tool in driving social change; ranging from the rights of workers to struggles for independence and emancipation. Solidarity discourse in global health reveals three critical gaps that must be addressed to move beyond rhetoric: conceptual ambiguity; epistemic injustice; and lack of tools for enactment and accountability. Our project addresses these gaps by engaging in an exercise of pluriversality that captures the multiple conceptualizations of solidarity, especially from historically marginalized groups: Latin America, Asia, Africa, Indigenous communities, and non-English speakers. Through an approach of incompletely theorized agreements, we interrogate the various conceptions to arrive at a set of core solidarity goals for global health. From these goals, we co-create, with key stakeholders and actors in global health, a solidarity index and ranking that enables actors to self-examine, transform, and be held accountable by stakeholders and the public.",,2027,University of Ghana,4058966.23,Human Populations,Unspecified,Adults (18 and older),Unspecified,Vulnerable populations unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Africa,Unspecified,,,,Ghana,,"Research to inform ethical issues | Policies for public health, disease control & community resilience",Research to inform ethical issues in Governance | Approaches to public health interventions,2023 +P30135,226080/Z/22/Z,"A web app for accessible, reproducible, multi-scale regression models for mapping climate driven infectious diseases.","The ability to predict risk of climate-driven, vector-borne and zoonotic diseases, at fine spatial resolutions, is important for directing public health policy, such as optimal targeting of vaccinations and managing health interventions. With disease cases commonly reported at a coarse county or state level, such high resolution predictions are crucially not often available. Disaggregation regression is a validated method that can address this gap, but is restricted due to the lack of user-friendly tools. Here, we aim to create an online app that reads in case data, fetches environmental data, fits disaggregation models and finally summarises predictions in policy- relevant ways. Importantly, we have agreements in place to co-design this tool with public health bodies working on vaccination programmes, and in countries affected by high-burden zoonotic and vector-borne diseases. We will use Lassa fever, a climate-sensitive, zoonotic disease as a case study, to demonstrate a user-friendly workflow that predicts fine-scale cases from areal level case data in Nigeria, in order to optimise vaccine distribution. We will then showcase the potential public health outcomes that can benefit from our tool, across a wide variety of diseases and geographical locations.",,2028,University of Leicester,485594.84,Human Populations | Other,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Unspecified | Not applicable,Non-Clinical,,Arenaviridae,,,,,,,,,Lassa fever,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P30136,222836/Z/21/Z,Integrated Surveillance Suite for Targeting Interventions to Cholera Outbreaks,"Infectious disease control requires ground-breaking, ultrasensitive biosensing technologies coupled with tools to monitor, predict and contain an outbreak's spread. Currently a range of infectious and potentially lethal diseases such as cholera, TB and HIV go undetected for too long while patients suffer as treatment is either non-existent or misguided. The global pandemic caused by COVID-19 has revealed the devastating health, economic and social consequences of the lack of diagnostic tools and integrated containment strategies. Moreover, too often uncontained diseases disproportionately impact LMICs. Advances in diagnostic technology, mobile-Health infrastructure, epidemiological frameworks, and data visualisation, make now an opportune time to further progress and integrate these efforts for the control of infectious disease. In this research programme, we will integrate these previously disparate strands into a comprehensive effort to fight cholera. We take a multidisciplinary approach, and as such engineers, biologists, computer scientists, materials scientists, chemists, physicists, mathematicians, and clinicians harness their individual expertise to collectively tackle the challenge to control cholera. By building on discoveries and insights we will deliver in this proposal, we aim in the longer run to deliver end-to-end efforts to contain other deadly diseases in geographies where they are most needed.",,2026,Imperial College London,3509955.09,Unspecified,Not applicable,Not Applicable,Not applicable,,Not applicable,Not applicable,,Other,,,,,,,,,Other,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Diagnostics | Impact/ effectiveness of control measures | Supportive care, processes of care and management",2023 +P30137,222510/Z/21/Z,Replication and Assembly of Influenza virus,"The theme of the proposed research is our understanding of the replication and assembly of Influenza virus, from a structural imaging perspective. The transcription and replication of the influenza virus genome occurs in the nucleus and the structure of the isolated polymerase reveals at a molecular level key steps in transcription and replication. The genome of Influenza virus is composed of 8 RNA segments each bound to the viral RNA polymerase and multiple copies of N protein to form ribonucleoprotein complexes (vRNPs). Newly replicated vRNPs are transported out of the nucleus, where they are trafficked to the cell membrane and assemble to form new viruses budding out from the cell membrane. How the production and assembly of RNPs is coordinated in the nucleus and the details of how the vRNPs are transported out of the nucleus to the cell membrane is unknown. By integrating structural, biochemical and cellular imaging, I aim to understand with atomic-level detail, vRNP production, nuclear export and viral assembly. This will be done using crystallography and single particle cryo-EM, combined with high resolution cellular EM and X-ray tomography, correlated with cryo- fluorescence imaging of infected cells to understand these key stages in the viral cycle.",,2027,University of Oxford,1938182.38,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P30138,228342/Z/23/Z,Identification of avian host factors underpinning Influenza A Virus (IAV) replication using CRISPR screens,"Influenza, commonly called flu', is a highly transmissible viral infection, which can infect multiple species including human, chicken, and pigs. As with all viruses, influenza is completely dependent on the host cellular machinery for its replication. It evades host defence mechanisms and use host cellular pathways for its replicative advantage. Understanding of these host virus interactions is the key for development of novel anti- viral therapeutics and for understanding of the viral host jump events which can help in devising control strategies. One way of understanding the host virus interactions is using high throughput genetic screens where host genes are individually deleted, or their expression is enhanced and the effect on viral replication is assessed. In this project I will use a newly developed genetic screen which uses modified influenza virus which can itself enhance host gene expression to affect its own replication. This screen will help in the identification of genes required for host defence and those exploited by virus for replication in the chicken host. The results will also enable us to compare the virus host dependency factors in chicken to those already known in humans.",,2026,University of Edinburgh,,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2023 +P30139,220125/Z/20/Z,Detecting Ebola at the Last Mile,"Ebola virus disease has been declared a Public Health Emergency of International Concern in Democratic Republic of the Congo. In the short term, our consortium plans to optimise, manufacture, and validate a novel Ebola rapid diagnostic test (RDT) for deployment at the point of need - that is low cost and high performance. A simple, 5 minute, high performance test, that complements complex laboratory tools, is urgently needed to ensure earliest possible detection of Ebola in the heart of communities experiencing an outbreak. Successful deployment will lead to an optimised and evaluated device for manufacture to support the current outbreak in DRC, surveillance in neighbouring regions, and in time post-DRC outbreak surveillance. In the long term, we envision substantial impact generated by establishing a new model for sustainable delivery of high performance outbreak diagnostics, deployed at the point of need. Accordingly, diaTropix - a new manufacturing facility dedicated to epidemics and neglected diseases in Dakar, Senegal - will be set up with the capability, expertise, and reagents to produce rapid diagnostics responsively to evolving outbreaks - with Ebola demonstrating proof of concept and feasibility, and a portfolio of rapid diagnostics in the pipeline for dengue, yellow fever, measles, and malaria.",,2022,Institut Pasteur de Dakar,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Filoviridae,,,,,,,,,Ebola virus disease,Wellcome Trust,United Kingdom,Europe,Africa,,,,,Senegal,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P30140,226472/Z/22/Z,Cripping Breath: Towards a new cultural politics of respiration,"Covid-19 emphasises the need for urgent new analyses of the politics, processes and prioritisation of respiration and ventilation. The sudden emergence of global respiratory disease has reshaped our social, cultural, and political worlds and embodied experiences of health and illness. This project centres the lives of people who have had their lives saved and sustained by ventilatory medical technologies. Respiratory failure is common in many health conditions, and is a symptom of Coronavirus. Our explorations, led by disabled, chronically ill and ventilated people, do so in recognition that these growing communities of people and patients are often absent from contemporary social theorisations of respiration and ventilation, but also that their experiences have much to teach about living in cultures of compromised respiration. Centring arts-informed, archival, narrative and ethnographic approaches, this project develops Crip perspectives - forms of knowledge production that emerge from lived experiences of disability and chronic illness. Artists-in-Residence, experts-by-experience, disability and arts organisations and clinicians will work in collaboration to curate and coproduce new understandings of the experiences of ventilated people, across a host of identity positions, to interrogate the new cultural politics of respiration and ventilation in a continuing global pandemic, and as we imagine post-pandemic futures.",,2028,University of Sheffield,2036054.3,Human Populations,Unspecified,Unspecified,Unspecified,Other,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Policies for public health, disease control & community resilience",Community engagement,2024 +P30141,225454/Z/22/Z,VICINITY-Understanding viral carriage in bioaerosols using dentistry as a model,"The COVID-19 pandemic has caused huge disruption to healthcare and millions of people are waiting for treatments. Dentistry has been badly affected because dental instruments like drills create tiny droplets of water which float in the air (aerosols). It's possible that viruses from our saliva (like the COVID-19 virus) could be carried in aerosols during dental treatment, however very few researchers have looked at this. Without better understanding the problem and how to control it, access to care will be severely affected in any other infectious disease outbreak in the future. We will use a virus that can't cause infections in people to see if viruses can can be carried in aerosols during simulated dental procedures in a mannequin, and how far they can travel. We will also measure bacteria and viruses in the air during routine dental treatment on patients. This research will help us understand how to control aerosols during healthcare procedures, and how we can better design equipment, clinics, and buildings to help. This is important in other areas of healthcare outside of dentistry, such as surgery, in hospital wards, and during general anaesthetics where there is a risk of viruses being transmitted in aerosols.",,2024,Newcastle University,,Human Populations | Viruses | Environment,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Dentists and dental staff | Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Infection prevention and control","Environmental stability of pathogen | Supportive care, processes of care and management | IPC in health care settings",2021 +P30142,226933/Z/23/Z,A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in COVID-19 (PLATCOV),"PLATCOV is an ongoing phase 2, open label, randomised, controlled adaptive platform trial. It is unique in providing a standardised quantitative comparative method for in vivo assessment of potential antiviral treatments in low-risk adults with early symptomatic COVID-19. The primary outcome is the rate of viral clearance measured as the slope of the log10 oropharyngeal viral clearance curve over the first 7 days following randomisation. The treatment effect is the multiplicative change in viral clearance rate relative to the no study drug arm. PLATCOV has recruited over 550 patients and provided definitive assessments of ivermectin (no effect), remdesivir (42% acceleration in viral clearance), casivirimab/imdevimab (60% acceleration in Delta, and approximately 20% acceleration in Omicron BA.2 and BA.5). This proposal is to continue PLATCOV in order to assess new antiviral drugs and monoclonal antibodies and combinations, to extend to five study sites across the world (continue in Thailand and Brazil, add Pakistan, Laos and an African site), and to conduct preliminary evaluations of a similar pharmacometric design to assess anti-influenza drugs. The final objective is definitive assessments of comparative antiviral effects in COVID-19, and initial establishment of a global platform for pharmacometric assessment of interventions in pandemic respiratory infections.",,2026,University of Oxford,191149.37,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,"Clinical Trial, Phase II",Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,Wellcome Trust,United Kingdom,Europe,Europe,,,,,United Kingdom,,"Therapeutics research, development and implementation",Phase 2 clinical trial | Therapeutic trial design,2024 +P30143,228271/Z/23/Z,Leveraging forecasts to optimise decision making,"The COVID-19 pandemic underscored the need for epidemic forecasts to guide policy decisions on resource allocation, public health measures, and risk communication. However, deriving outputs from epidemic forecasts that provide answers to the questions that public health practitioners and policy makers actually have is not commonly done. Additionally, historical forecasts are frequently not openly accessible for forecast performance to be evaluated, which makes it harder for policymakers looking to gauge the reliability and trustworthiness of a forecast and determine the extent to which its predictions should influence subsequent public-health decisions. Our proposal aims to close the interpretability gap that precludes optimal use of epidemic forecasts. We will first conduct a series of structured interviews with public health practitioners and external stakeholders to better define unmet needs around epidemic forecasting and identify common policy-relevant needs. Secondly, we will develop a software package and web-based tool aimed at enabling policymakers, especially in contexts where technical capacity is limited, to better understand, interpret and action epidemic forecasts. Our vision is to develop a computational tool to retrospectively assess forecast accuracy, defining accuracy based on policy-relevant derived statistics identified from our initial interviews, and transform them into interpretable and actionable information.",,2025,Imperial College London,100694.64,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel | Other,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Epidemiological studies | Policies for public health, disease control & community resilience",Impact/ effectiveness of control measures | Policy research and interventions,2024 +P30144,226816/Z/22/Z,Investigating the genetic and epigenetic basis of immune response to SARS- CoV-2 vaccination,"During the COVID-19 pandemic, mass vaccination schemes were rolled out in an unprecedented international action to curb and contain viral spread. Human immune response to COVID-19 vaccination varies between individuals, with some individuals at risk of mounting a low response to vaccination. While we know that people with immunosuppression or immunodeficiency do not respond well to vaccinations and are at risk of severe disease, in other individuals the basis for a poor vaccine response is unknown. We therefore cannot predict poor responders to COVID-19 vaccination in other individuals and have a limited understanding of the underlying genetic and epigenetic mechanisms contributing to this extreme response. I aim to utilize the national COVID-19 Infection Survey (CIS) to study individuals with extreme responsiveness to vaccination in the general UK population and understand the genetic contributions to vaccine response using both serological and cellular immune profiling. I will attempt to identify genetic factors driving differences in the immune response to vaccination, then further investigate factors correlated with the low response using multiple follow-up experiments as these identified factors can potentially act as biomarkers that may be used to predict vaccine response in the future and help inform vaccine design.",,2026,University of Oxford,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2022 +P30145,222907/Z/21/Z,Risk factors for SARS-CoV-2 infections and outbreaks in care home staff and residents,"In 2020, over one in four people who died from COVID-19 infection in England lived in a care-home . Reducing deaths in this vulnerable group by protecting them from infection using approaches like vaccination, is a priority. To understand if these work, and who has the biggest risk of getting infected, we need to know how many people have had the infection and how this affects their immune system. However, we cannot do this yet as collecting this information is difficult. To answer these questions, researchers from UCL have set up the VIVALDI study, one of the biggest studies of COVID-19 in care-homes. Care-home staff and residents who take part have repeated swab testing to find out who is infected, and blood testing to see who had COVID-19 before. Information is collected about hospital admissions and deaths in these people, and about the care-homes themselves, like size. Using this information, I will find out which care-homes have had the most infections, who is most likely to get infected, and in people who have been infected or vaccinated, how long they are protected for. The results will help government officials understand which changes can prevent COVID-19 and other infections in care-homes.",,2023,University College London,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,United Kingdom,,Epidemiological studies,Disease susceptibility,2020 +P30146,225168/Z/22/Z,Combatting Covid 19 Variant,"Funding will go toward critical R&D to meet the challenges of this rapidly evolving pandemic & facilitate equitable access to safe effective vaccines. Objectives are: - Enable equitable access to vaccines to reduce circulation of virus-thereby limiting opportunities for viral mutation-and reducing the disease burden on health systems. - Create conditions where vaccines can be rapidly adapted (within 100 days) to the new strains, and increase manufacturing capacity to make enough for global need - Optimise and deploy the existing suite of vaccines, including through the testing of 'mix and match' regimens and booster doses. - Support development of new strain- specific vaccines and second-generation vaccines that are more robust to viral evolution - Accelerating development of breakthrough vaccine candidates Funding would support: - Next generation vaccine candidates with potentially significant health impacts, e.g. candidates that elicit mucosal immunity or single dose candidates. Scale-up development of promising candidates. - Expanding CEPI's ""Agility Programme"" to understand the impact of variants on vaccine efficacy & support decision making on the need to adapt existing vaccines. - Building protection against variants to prepare for the emergence of potential new variants. - Developing a broadly protective coronavirus vaccine that could eliminate the risk of existing coronaviruses & new, unknown coronaviruses.",,2023,Coalition for Epidemic Preparedness Innovations (CEPI),24204257.89,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,Wellcome Trust,United Kingdom,Europe,Europe,Unspecified,,,,Norway,,"Vaccines research, development and implementation",Pre-clinical studies,2022 +P30147,0142006050,Health literacy survey Vaccination Switzerland 2024-2025,"During the fight against Covid-19, the topic of vaccination took on particular importance, politically, in the media and also among the general population. It can be assumed that the health literacy regarding vaccinations in the population has changed during the pandemic years. For this reason and in order to support this assumption with evidence, a follow-up study of the mandates carried out in 2018 on health literacy regarding vaccinations in the Swiss population and the knowledge and attitudes towards vaccinations in healthcare professionals is to be carried out as part of the National Strategy on Vaccinations (NSI).",,-99,N/A,288231.97,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Health Systems Research",Vaccine/Therapeutic/ treatment hesitancy | Health workforce,2024 +P30148,142006594,Covid-19: SARS-CoV-2 genomic surveillance,"The aim of this contract is to ensure national genomic surveillance of the SARS-CoV-2 virus. This virus can change continuously through mutations, meaning that several variants can be circulating. The focus of genomic surveillance will be on virus variants that cause severe disease and lead to hospitalization, as well as virus variants that could impact clinical care or the effectiveness of vaccination, as well as samples from the Sentinella reporting system. In addition (outside of this contract), sequencing of wastewater samples (wastewater monitoring) will be carried out to monitor circulating virus variants in the population. The subsidy from this contract enables the continuation of the national genomic surveillance program for the SARS-CoV-2 virus. The surveillance program includes a network of laboratories ...",,-99,N/A,1641343.5,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2024 +P30149,142006587,Genomic surveillance of infectious diseases in wastewater 2024-2025,"Continuous genomic monitoring in wastewater makes it possible to obtain a timely overview of the SARS-CoV-2 virus variants currently circulating in Switzerland. This makes it possible to identify virus variants that are resistant to vaccinations or medications or that lead to severe illnesses. In addition, their relative frequencies can be estimated. This is relevant in order to take early measures if necessary. Genomic monitoring includes:- sequencing of SARS-CoV-2 gene fragments in wastewater samples, - bioinformatic analysis of the raw sequence data to detect SARS-CoV-2 virus variants and their relative proportions, - testing the applicability of this methodology for other respiratory viruses.",,-99,N/A,844483.9,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2024 +P30150,1.23.08,Metagenomic virus-screening of wild bird samples from Piano di Magadino (TI) by next generation sequencing,"As part of a project by the Scuola universitaria professionale della Svizzera italiana (SUPSI), wild birds in the Magadino plain are being sampled and specifically tested for known pathogens such as West Nile virus and avian influenza. At the same time, the occurrence of mosquitoes in this area is being investigated with the aim of better understanding the dynamics and interactions between mosquitoes and birds, as well as their influence on virus transmission. The birds are caught with nets using a special permit (nature reserve) and the sample material taken (choanae and cloaca swabs, as well as blood sample) is therefore limited and very valuable. However, only a very small proportion of the potentially present viruses can be tested with specific diagnostics (PCR, ELISA). In order to use this valuable sample material as efficiently and widely as possible, we propose to test the samples nonspecifically using NGS for all known and especially potentially zoonotic / mosquito-borne viruses (virome analysis). These results would add weight to the SUPSI study and provide valuable information for early detection of ""new""/unexpected viruses circulating in these birds. This knowledge could in turn be used in future studies to investigate the circulation of viruses between birds and mosquitoes (and potentially humans) using specific diagnostic methods.",,-99,N/A,16829.23,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Other,Other,,,,,,,,Pandemic-prone influenza | Other,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease surveillance & mapping",2023 +P30151,142006132,In-depth analysis of vaccination coverage data,"To assess whether the Covid-19 pandemic has had an effect on the vaccination coverage of children and adolescents and whether the vaccination recommendations against diphtheria, tetanus and pertussis (DTP) adjusted in 2019 are being implemented as recommended, the vaccination rates calculated as standard as part of the cantonal vaccination monitoring are not sufficient. Additional in-depth analyses were therefore commissioned by the FOPH. The objectives of these analyses are: 1. To determine trends in DTP uptake for 2-year-old children between 2017-2019 and 2020-2022. 2. To evaluate the vaccination rates of selected vaccinations before the pandemic and compare them with the vaccination rates during and after the pandemic.",,-99,N/A,33260.83,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research","Indirect health impacts | Medicines, vaccines & other technologies",2023 +P30152,142006108,Wastewater monitoring of communicable diseases,"This wastewater monitoring makes it possible to estimate the circulation of SARS-CoV-2, influenza viruses A and B and respiratory syncytial viruses (RSV) in Switzerland in a timely manner. Wastewater monitoring includes: - regular analysis of wastewater samples for gene fragments of SARS-CoV-2, influenza A and B and RSV - quantification of the gene fragments of these viruses - further development of the methodology, if necessary - testing the applicability of this monitoring for other pathogens",,-99,N/A,1460779.72,Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2023 +P30153,0142005593,CH-SUR Hospital based surveillance 2023,"Hospital-based Covid-19 and influenza surveillance system. The aim of this surveillance is to obtain detailed clinical and epidemiological information on the disease burden, clinical course (such as treatment in the intensive care unit) and risk factors. This is necessary in order to be able to take appropriate measures in a timely manner and to determine the effectiveness of the prevention measures.",,2023,N/A,2402514.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2023 +P30154,142005806,Mandate Modelling and Method Consulting for Surveillance,"As part of surveillance, there is a need for statistical modelling of communicable diseases (especially Covid-19). The FOPH has commissioned the Institute for Social and Preventive Medicine (ISPM) at the University of Bern to carry out the necessary statistical modelling and to advise the FOPH on methodological issues. This includes in particular the analysis of excess mortality and the (retrospective) analysis of Covid-19 monitoring in Switzerland.",,-99,N/A,159582.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease susceptibility | Impact/ effectiveness of control measures | Disease surveillance & mapping,2023 +P30155,142005748,Mpox virus (MPV) asymptomatic transmission study during the outbreak in 2022,"An outbreak of monkeypox virus (MPV) has been observed worldwide since May 2022. Unlike previous outbreaks, the chain of transmission appears to be continuing among people, especially among men who have sex with men (MSM). One hypothesis for this ongoing transmission is that, contrary to previous assumptions, asymptomatic carriers of the virus exist. These could be the driving force behind these transmission chains. The University of Zurich therefore wants to study asymptomatic MSM who are at risk of MPV infection. The study results can help improve the strategy for containing the virus: With the detection of asymptomatic carriers, testing recommendations can be adjusted.",,2023,N/A,26936.17,Human Populations,Unspecified,Adults (18 and older),Unspecified,Sexual and gender minorities,Unspecified,Unspecified,,Poxviridae,,,,,,,,,Mpox,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Clinical characterisation and management,Disease transmission dynamics | Disease surveillance & mapping | Disease pathogenesis,2023 +P30156,142005709,Covid-19: SARS-CoV-2 genomic surveillance,"The subsidy from this contract enables the continuation of the national genomic surveillance program for the SARS-CoV-2 virus. Genomic surveillance focuses on virus variants that cause severe disease and lead to hospitalization, as well as virus variants that could impact clinical care or the effectiveness of vaccination, and samples from the Sentinella reporting system. The surveillance program includes a network of laboratories coordinated by CRIVE. The subsidy covers the coordination of the surveillance program, the sequencing of the viral genome, and the analysis and publication of the data obtained.",,2024,N/A,1934567.53,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2023 +P30157,0142005779,Literature research on Sars-CoV-2 and Covid-19,"As part of this assignment, the international scientific literature on selected topics relating to Sars-CoV-2 and Covid-19 will be reviewed and relevant publications will be compiled and summarized. The aim is to ensure that the FOPH and other authorities are always informed about the current state of knowledge on the new coronavirus. The management of the Covid-19 pandemic is highly dependent on an overview of the latest scientific findings. The number of scientific publications on this topic is increasing exponentially, which is why the FOPH relies on the support of experts in its review.",,2023,N/A,702270.27,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,,,2022 +P30158,142005507,National Reference Centre for Influenza 2022-2025,"Influenza viruses can cause seasonal epidemics, but can also trigger pandemics. This is why flu is monitored in Switzerland through the voluntary Sentinella reporting system. However, flu-like illnesses can be caused by more than just influenza viruses, and there are also different types and subtypes of influenza with different virulence properties. For the timely monitoring of influenza and the timely, situation-appropriate adaptation of recommendations and measures to protect the population, additional information on circulating influenza viruses and their changes (antigenic drift, antigenic shift, development of resistance) is therefore important. Due to the Covid-19 pandemic, the aim is also the virological monitoring of SARS-CoV-2 and other respiratory viruses. The goals of virological monitoring are: - Detection of influenza, SARS-CoV-2 and other respiratory viruses in ...",,-99,N/A,1436051.07,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2022 +P30159,0142005576,Estimating the burden of care related to long-COVID in family medicine in Switzerland: a study within the Sentinella network,"The purpose of this study is to assess the impact of post-Covid disease on the healthcare system. The study is intended to help identify the healthcare needs of the affected patient population. This project will conduct an analysis of the frequency and evolution of the number of consultations for post-Covid-19 patients over time, based on data collected in the Sentinella system since July 2021 (expected to October 2023). In addition, more detailed data collected prospectively by doctors in the Sentinella network on a small number (up to 3) of consultation patients with post-Covid-19 disease over a period of 12 months will be evaluated. The study is thus intended to help identify the healthcare needs of the affected patient population. The study aims to 1) characterize the patient population with long Covid, 2) describe the needs of long Covid patients in terms of assessment and referrals, and 3) quantify the need for inpatient, institutional or home care. The study is intended to help identify and plan health care needs.",,-99,N/A,84793.98,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences",2022 +P30160,0142005547,Corona Immunitas research program of SSPH+ on the spread and impact of Covid pandemic in Switzerland.,"With the continuation of the study already ongoing until the end of 2022, important information on seroprevalence in the Swiss population will be investigated. These findings provide an additional basis based on evidence-based scientific data, which will serve to develop strategies and recommendations as the pandemic progresses and in particular in view of a possible wave of infections in autumn 2022. The main objectives of the SSPH+ Corona Immunitas program to determine SARS-CoV-2 immunity and the effects of the pandemic in Switzerland in this phase (5 & 6) are: 1. Determination of seroprevalence in the population as a result of SARS-CoV-2 infection and/or COVID-19 vaccination, 2. Determination of the proportion of the population with a previous SARS-CoV-2 infection (recovered) without vaccination, 3. Determination of the extent and duration of immunity after infection with SARS-CoV-2 ...",,2023,N/A,1372788.62,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease surveillance & mapping | Disease pathogenesis | Characterisation of vaccine-induced immunity,2022 +P30162,ExSt.2023.1448,"End-term Evaluation - Enhancing Agro Pastoral Food Security, Livelihoods and Protection (VSF), South Sudan","The Enhancing Agro-Pastoral Food Security, Livelihoods and Protection (PROWIGA II) Project which was aimed at improving protection of vulnerable groups, enhanced access to nutritious diets, diversified livelihoods and incomes and mitigated potential Covid-19 spread among targeted beneficiaries in Juba, Aweil East and Panyijiar Counties",,2022,N/A,5028.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts | Economic impacts,2022 +P30163,0142005426,Social inequality and severe COVID-19 trajectories in the Swiss migrant population,"This project contributes to measuring health equity through improved data use (see Health2030). The aim is to use data from hospital medical statistics combined with census data to document possible social inequalities in the migrant population with regard to severe Covid-19 courses (risk factors, vulnerable groups). Furthermore, qualitative methods will be used to identify obstacles and needs for successful coping among these vulnerable groups. The results are intended to support decision-makers and actors in the health and social sectors in better targeting future health care to vulnerable target groups.",,-99,N/A,147541.74,Human Populations,Unspecified,Adults (18 and older),Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,Data Management and Data Sharing,,,,,Research to inform ethical issues | Epidemiological studies,"Research to inform ethical issues related to Social Determinants of Health, Trust, and Inequities | Disease susceptibility",2022 +P30164,0142005478,Expertise: Sars-CoV-2 vaccines and immunological surveillance,"This mandate is intended to review the scientific literature available worldwide on the subject of vaccines against Sars-CoV-2 and immunological monitoring and to make the findings available to the FOPH. Until October 2022, regular summary reports will be prepared on the latest global findings on vaccines against Sars-CoV-2, e.g. on effectiveness or side effects, as well as on immunological parameters, e.g. on the protective correlate of SARS-CoV-2 antibodies and cellular immune reactions, on the duration of long-term protection after immunization (vaccination and/or infection) or on the level and duration of protection in risk groups. The publications considered will be provided to the FOPH in a suitable format.",,2022,N/A,132500.38,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Adverse events associated with immunization | Characterisation of vaccine-induced immunity,2022 +P30166,142004701,Revision EpidA: Regulatory Impact Assessment - Part 1,"On June 19, 2020, the Federal Council commissioned the FDHA to start a partial revision of the Epidemics Act (EpG). The law is intended to enable the federal government and the cantons to work closely together to protect the health of the population from future threats from communicable diseases and to take the necessary precautionary measures in good time. The revised law addresses the findings from the implementation of the EpG before the Covid-19 pandemic, the findings from the Covid-19 response, but also new developments, e.g. with regard to digitalization. The regulatory impact assessment (RFA) is an instrument for examining and presenting the economic effects of federal proposals. This RFA examines the impact of the revised EpG.",,2023,N/A,125427.97,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Policy research and interventions,2022 +P30167,0142005382,Prospective cohort studies on immunosurveillance of SARS-CoV-2 in Switzerland,"With the continuation of the twin study, which is already ongoing, until the end of 2023, important information on the immunological status of the Swiss population will be investigated. These findings provide an additional basis based on evidence-based scientific data, which will be used to develop strategies and recommendations as the pandemic progresses and in particular in view of a possible wave of infections in autumn 2022. The two cohort studies ""Zurich Coronavirus Cohort Study"" (ZSAC) and ""Zurich Coronavirus Vaccination Study"" (ZVAC) are population-based, prospective cohort studies that observe representative populations of 1552 recovered (ZSAC) and 575 vaccinated people (ZVAC) respectively since the time of infection with SARS-CoV-2 or vaccination. In March 2022, a follow-up of over 18 months for the ZSAC study and a 10-month follow-up resulted...",,2023,N/A,491809.92,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2022 +P30168,7270341,Recoding the SARS-CoV-2 genome - A multidisciplinary approach to generate live-attenuated coronavirus vaccines,"Compared to the first generation vaccines, the vaccine differs in four ways. It offers a longer-term immune response that is created by the activation of T cells. The vaccine is effective despite mutations of the coronavirus spike protein because it contains all viral proteins and not just the spike protein. In addition, nasal administration in the form of a nasal spray is possible and the vaccine remains stable even at higher temperatures.",,-99,N/A,2565896.46,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2022 +P30169,0142005241,Covid-19: respiratory repercussions of long COVID,"The purpose of the study is to better understand the subsequent damage to the lungs after an acute infection. The identification of organ damage to the lungs and/or permanent symptoms is the basis for any studies on therapeutic approaches. For this purpose, a cross-lingual, multicenter (9 centers) observational study was initiated in Switzerland to assess questions about subsequent damage to the lungs after COVID-19. Previous illnesses and symptoms were recorded by interviewing the treating physician or using questionnaires. In addition, in the case of breathing difficulties, an assessment of the lungs was recorded using lung function, stress tests and radiological examinations. Blood was also taken from the patients to test for possible biomarkers. The primary goals of the study are to describe the COVID-19 characteristics, diagnostic clarification and treatment choice after an acute infection. The long-term...",,2023,N/A,137131.55,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,Post acute and long term health consequences,2022 +P30170,0142005238,Covid-19: Burden of COVID-19 in long-term-care facilities in Eastern and Western Switzerland,"The disease burden of COVID-19 among residents of retirement and nursing homes (RNH) is high; depending on the country, 30-50% of COVID-19-associated deaths were measured in long-term institutions. In Europe, RNHs are the most common setting for COVID-19-related outbreaks. Little is known about the risk factors associated with a high disease burden in these institutions. In addition, it must be taken into account that certain measures have a major impact on the quality of life of residents and these should also be evaluated.The objectives of the project are:- To describe the COVID-19-related disease burden, expressed as COVID-19 illnesses, hospitalization rates, total and COVID-19-related mortality, and immunity/vaccination rates among residents and staff - To evaluate factors associated with a higher COVID-19-related disease burden, which...",,2022,N/A,63819.66,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Indirect health impacts,2022 +P30171,0142005131,Ciao Corona school study on the spread of the SARS-CoV-2 virus in school children,"Ciao Corona is a population-based cohort of around 2,500 schoolchildren (ages 6 - 17 years) from randomly selected schools (n = 55) and classes (n = 275) from all districts of the canton of Zurich. The children and adolescents are invited to test for antibodies against the SARS-CoV-2 virus. The study has been investigating the longitudinal development of seroprevalence and development of immunity as well as lifestyle and health in children and adolescents since summer 2020.The main objectives of Ciao Corona for phases 4 and 5 are:1. Determination of SARS-CoV-2-related, natural and vaccine-related immunity in children and adolescents and the temporal course of immunity since the beginning of the pandemic2. Characterization of symptoms, their course and risk constellations for long COVID3. Determination of the mental health and well-being of children and adolescents and the connection ...",,2023,N/A,452018.25,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease surveillance & mapping | Post acute and long term health consequences | Characterisation of vaccine-induced immunity,2022 +P30172,0142005093,Wastewater monitoring of SARS-CoV-2,"Based on the Eawag/EPFL research project, measuring the Sars-CoV-2 virus concentrations in wastewater has proven to be a good tool for estimating the epidemiological situation regardless of testing capacities and the testing behavior of the population. With the planned national wastewater monitoring, the measurements are to be continued on a larger scale for the whole of Switzerland in order to obtain a regionally resolved overview of the epidemiological situation. Around 100 wastewater treatment plants (WTPs) across Switzerland are sampled 3-6 times a week and the samples are analyzed in 12 different laboratories. The laboratories are subjected to regular ring tests, supervised by the Zurich Cantonal Laboratory. The cantonal environmental and water protection authorities require the laboratories to take part in the ring tests and to report the laboratory results to the FOPH. The federal government reimburses the cantons for the analysis and reporting costs.More...",,-99,N/A,7596316.06,Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2022 +P30174,0142004996,SARS-CoV2 infection in children in Switzerland,"Knowledge about disease progression in children and adolescents infected with SARS-CoV-2 is limited. This project aims to help close this knowledge gap. Various parameters are collected from children and adolescents treated for COVID-19 in hospitals in Switzerland in order to gain insights into the incidence, clinical manifestation and severity of the disease, PIMS-TS (Multisystem Syndrome Temporally related to SARS-CoV-2), disease progression and treatment options.",,-99,N/A,274813.46,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies | Clinical characterisation and management,"Disease surveillance & mapping | Prognostic factors for disease severity | Disease pathogenesis | Supportive care, processes of care and management",2021 +P30175,0142004995,CoMix CH - a longitudinal social contact survey,"When dealing with the COVID-19 pandemic, it is important for authorities to know how the population perceives what is happening, how they assess risks and how this determines their contact behavior. As part of this study, a representative sample of the Swiss population is regularly surveyed on these topics. This study is part of a cross-country longitudinal study in Europe, which enables a comparison across different countries, including Great Britain, the Netherlands and Belgium. In Switzerland, the project started in January 2021 and was funded by the EU Commission until September 2021. The surveys are now to continue until March 2022.",,2022,N/A,113127.9,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions,2021 +P30177,0142004932,"Covid-19: RISC-19-ICU Registry, endorsed by the Swiss Society of Intensive Care Medicine 2021 - 2022","Since March 2020, the Institute of Intensive Care Medicine at the University of Zurich has been using the RISC-19-ICU Register to collect detailed data on the physiological and therapy-associated characteristics of patients admitted to an intensive care unit, the course of these characteristics during intensive care, and the clinical outcome. In addition to the direct relevance of the register for the medical understanding of Covid-19 and for the effects of measures (such as the vaccination campaign), these data, which are representative across Switzerland and for various hospital types, in combination with epidemiological data, offer a quantitative insight into developments in intensive care units. In order to ensure our own knowledge needs in adaptation to the changing epidemiological situation, the ""continuation of the register for the ongoing monitoring of critically ill COVID-19 patients in Swiss intensive care units"" is therefore being planned.",,2022,N/A,362692.36,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management,"Supportive care, processes of care and management",2021 +P30178,0142005204,Covid-19: rapid appraisal of health services for long term effects of covid-19,"The study commissioned by the BAG records and analyses the situation of care (treatment + rehabilitation) of people suffering from the long-term consequences of a Covid-19 infection. Its purpose is also to identify any gaps in care and to derive appropriate recommendations. The content of the study is an analysis of the situation in the area of ​​general practitioners, specialised contact points and inpatient and outpatient rehabilitation.",,2022,N/A,158778.78,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Clinical characterisation and management | Health Systems Research,Post acute and long term health consequences | Health service delivery,2021 +P30179,0142004897,"Covid-19: Pro Juventute Report: Impact of the Covid 19 Pandemic on Children, Adolescents and their Families in Switzerland","The Pro Juventute Corona report shows how the Covid-19 pandemic and its accompanying circumstances are having a far-reaching impact on the health, well-being and development of young people in Switzerland. Although the medium and long-term consequences of the corona crisis cannot yet be precisely assessed, it is already clear that children and young people in Switzerland are also under great stress and that pre-existing problems and inequalities are being accentuated. The report is a research overview of the studies and investigations available for Switzerland up to June 2021 with a focus on the effects on the mental health of young people. It is a nationwide report, which in this respect ensures representativeness for the language regions (or individual cantons).",,2021,N/A,18889.87,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P30181,1.21.15,Investigations on the potential role of free-ranging wildlife as a reser-voir of SARS-Coronavirus-2 in Switzerland,"The ongoing COVID-19 pandemic is having a dramatic impact on human society. Although the source of the virus remains unclear, everything points to its origin in wild animals. It is also becoming increasingly clear that a large number of domestic and wild animal species are susceptible to SARS-CoV-2 infection, which has led, among other things, to the recommendation to include wild animals in infection surveillance. COVID-19 is a typical example of a disease that should be investigated using a One Health approach. To date, there is no information on the virus prevalence or the possible role of wild animals living in the wild as a virus reservoir in Switzerland. The aim of this study is to examine various wild animal species for possible SARS-CoV-2 infection. Based on the postulated susceptibility and risk of infection, the following species are primarily being investigated: felids (European wildcat, Eurasian lynx), canids (gray ...",,2023,N/A,62921.22,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease surveillance & mapping,2021 +P30183,0142004802,Population survey and baseline study on vaccination scepticism in population segments regarding covid-19 vaccination Enquête de population et étude de base sur le scepticisme envers la vaccination contre le COVID-19 dans des segments de population,"The aim of this survey is to determine the profile/characteristics of groups of people who are skeptical about vaccinations. The aim is to get answers to the central question of which people are currently unvaccinated but would be willing to get vaccinated (so-called ""latent willingness to be vaccinated""). The results are intended to identify measures that promote vaccination and, conversely, vaccination hurdles in order to reach those who are at least latently willing to be vaccinated and encourage them to get vaccinated.",,2022,N/A,61212.48,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Vaccine/Therapeutic/ treatment hesitancy,2021 +P30184,86,Short-time work during the coronavirus crisis,"In order to cushion the economic consequences of the COVID-19 pandemic, the Confederation has relied heavily on short-time work for employees. The evaluation examines whether the adjustments made to the law during the crisis were expedient, whether the support provided by the Confederation to the relevant authorities in the cantons was appropriate, and whether the supervision and controls are effective in preventing fraudulent claims.",,2023,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Economic impacts,2021 +P30185,0142004794,Covid-19: Impact of the COVID-19 pandemic on inpatient procedure volumes in Switzerland,"The project examines the impact of the Covid-19 pandemic on the number of inpatient procedures performed in Switzerland since the beginning of the pandemic. In a first step, claims data from a large Swiss health insurer will be used to create two patient cohorts: one in the years 2017-2019 (control years) and one in 2020 (pandemic year). In a second step, data from the Federal Statistical Office will be used, which contains information on all hospital stays in Swiss hospitals. The project places a special focus on non-Covid-19 related healthcare in the areas of cardiovascular, orthopedic and oncological procedures. The aim is to create a sound data basis and to identify vulnerable populations in terms of under-provision.",,2022,N/A,16364.01,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures | Health Systems Research",Indirect health impacts | Health service delivery,2021 +P30186,0142004789,COVID-19: Vaccine hesitancy among school staff in Switzerland: A mixed-methods study 2021-2022,"A mixed-methods project to measure and explore COVID-19 vaccine uptake, intention to get vaccinated, reasons for uptake and factors associated with intention, among a sample of individuals working in public and private nurseries, kindergartens, primary schools, and after schools across German-, French-, and Italianspeaking Switzerland. - The first objective of the project is to measure COVID-19 vaccine uptake, intention to get vaccinated, reasons for uptake and factors associated with intention, in a large sample of individuals working in public and private nurseries, kindergartens, primary schools, and after-schools in Switzerland. - The second objective of the project is to explore and understand the attitudes and beliefs regarding COVID-19 vaccines, and experiences with the COVID-19 vaccination, among a small sample of individuals working in public and private nurseries, kindergartens, primary schools, and after-schools in Switzerland.",,2022,N/A,87889.45,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Vaccines research, development and implementation | Policies for public health, disease control & community resilience",Phase 2 clinical trial | Vaccine/Therapeutic/ treatment hesitancy,2021 +P30187,0142004636,Detection of SARS-CoV-2 in the wastewater of selected wastewater treatment plants: obtaining basic data for the establishment of a national monitoring system,"EAWAG analyses the wastewater from 6 sewage treatment plants across Switzerland every day for the presence of SARS-CoV-2 RNA. The aim is to use this data to estimate the spread of SARS-CoV-2 in the Swiss population, in addition to determining the number of cases. In addition, experience with the analysis of wastewater will be collected that can be used to set up a national monitoring system. This includes, for example, an estimate of how well wastewater analyses can predict the course of the pandemic when the number of cases is low or which criteria should be taken into account when selecting WWTPs for monitoring.",,2023,N/A,1531002.67,Environment | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease surveillance & mapping,2021 +P30188,0142004663,Driver infections COVID-19,"When dealing with the COVID-19 pandemic, it is crucial to know where people are becoming infected with the virus. This research project is collecting data on places of infection. Mobility data from selected people who have agreed to the tracking of their cell phone data and the use of this data for research purposes has been available almost without interruption since the beginning of the pandemic. These people are being asked whether and, if so, when they have had a Covid infection or received a positive test result. By linking this information with the mobility data, an attempt is being made to identify information on places of infection.",,2022,N/A,144877.5,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Impact/ effectiveness of control measures | Disease surveillance & mapping,2021 +P30189,0142004645,Covid-19 Vaccination in Switzerland: Information and Misinformation on Social Media,The research project examines the reception and dissemination of information regarding the Covid-19 vaccination in Switzerland on social media. The study will show to what extent key statements/messages from the authorities regarding the Covid-19 vaccination are adopted and disseminated on social media and how this information and its sources are evaluated. The findings on the reception and dissemination of information and disinformation will be compared in order to be able to assess the role of disinformation in shaping the public's opinion on the subject of Covid-19 vaccination.,,2022,N/A,64611.31,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience",Communication,2021 +P30190,0142004623,"Covid-19: SEROCOV-Kids; Establishment of a digital cohort to monitor the impact of the Covid19-related sanitary crisis on mental and physical health, development and general well-being of children and adolescents","The project aims to carry out an observational study among children and adolescents in Geneva (1 to 17 years), with the objective of putting in place a population-based sentinel system to evaluate the impact of the COVID-19 epidemic on various dimensions of health and development and monitor socioeconomic inequalities in health outcomes of this generation of children and adolescents. The aims of the project are To estimate the impact of the COVID-19 crisis on children's health behaviors To assess the impact of the COVID-19 crisis and related confinement/isolation on children's physical and mental health and To estimate the role of individual and neighborhood socio-economic factors in shaping the impact of the COVID-19 crisis To assess the impact of the direct and indirect consequences of the COVID19 epidemics on social inequalities in health outcomes and model the long-term lifecourse impact on social and health trajectories To examine the effects of long-covid in children The following are included in this study: Serology at baseline and after 18 months Inclusion of a population of migrant and socially vulnerable children from the pediatric outpatient clinic in HUG, Inclusion of a population of children with disabilities and chronic diseases (clinically vulnerable) Long term follow-up of seropositive children for long-covid in children",,2023,N/A,110894.98,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Children (1 year to 12 years),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Epidemiological studies | Clinical characterisation and management | Secondary impacts of disease, response & control measures",Disease surveillance & mapping | Post acute and long term health consequences | Indirect health impacts | Social impacts,2021 +P30191,0142004547,Coronabambini - a sequential mixed method evaluation,"The online decision support tool www.coronabambini.ch (""Coronabambini"") was developed to support the pediatric COVID-19 testing and quarantine strategy of the Federal Office of Public Health (FOPH). The tool has been integrated into the FOPH's Corona Checker since December 2020 and its aim is to - support pediatric patients and their caregivers in making decisions about testing and attending schools and daycare centers, - relieve primary care providers of the burden of answering patients' requests for information related to COVID-19, and - support the FOPH's efforts to streamline testing and public information.The tool has already been quantitatively evaluated. A supplementary qualitative study (survey) is the subject of this project, which aims to answer the following questions: - How and why is Coronabambini used as an online decision support tool...",,2022,N/A,87111.52,Human Populations,Unspecified,Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Caregivers,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,Digital Health,,,,,Health Systems Research,Health service delivery,2021 +P30192,0142004546,"Stress and mental health among children/adolescents, their parents, and young adults one year after the first COVID-19 lock-down in Switzerland","This study aims to assess different stressful situations and the psychological impact of the Corona pandemic and its measures among adolescents between 12 and 24 years of age in Switzerland. Items on suicidality and suicide ideation among adolescents will also be included in the study.The study repeats the same questions and uses part of the same sample as two studies conducted in 2018 and 2020. In this way, the data collected can be compared with the data before and at the beginning of the pandemic.",,2022,N/A,55622.09,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older),Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2021 +P30193,0142004557,Literature research on Sars-CoV-2 and Covid-19,"As part of this assignment, the international scientific literature on selected topics relating to Sars-CoV-2 and Covid-19 will be reviewed and relevant publications will be compiled and summarized. The aim is to ensure that the FOPH and other authorities are always informed about the current state of knowledge on the new coronavirus. The management of the Covid-19 pandemic is highly dependent on an overview of the latest scientific findings. The number of scientific publications on this topic is increasing exponentially, which is why the FOPH relies on the support of experts in its review.",,2022,N/A,995117.36,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,,,2021 +P30194,0142004578,"Parchemins: Evaluation of the impact of the Papyrus regularisation programme on the health, living conditions and economic situation of sans-papiers migrants in Geneva - COVID-19 section","The Parchemins project supported by the OFSP evaluates the impact of the Papyrus regularization program on the health, living conditions and economic situation of undocumented migrants in Geneva. This support specifically focuses on the study of impact of the Papyrus regulation program on the health, living conditions and economic situation of undocumented migrants in Geneva during the COVID-19 pandemic. The aim is to better understand the impact of COVID-19 on the population undocumented migrant and those recently regularized, particularly with regard to the assessment of health risks linked to COVID-19 and the intention to participate in the vaccination campaign.",,2022,N/A,21839.7,Human Populations,Unspecified,Unspecified,Unspecified,Internally Displaced and Migrants,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Policies for public health, disease control & community resilience | Secondary impacts of disease, response & control measures",Vaccine/Therapeutic/ treatment hesitancy | Indirect health impacts,2021 +P30195,142004492,Importance of SARS-CoV-2 Infections in Animals of COVID-19 Affected Households and Influence of Hygiene Standards,"The One Health aspect of COVID-19 affected households with pets as virus hosts and potential reservoirs, as well as their influencing factors, have not yet been sufficiently researched. So far, recommendations on how to deal with animals in or from COVID-19 environments are mainly based on assumptions. Pets have a great importance in our society. People live closely together with their animals and pets play an important role in people's mental and physical well-being, especially during the pandemic and lockdown situation. Therefore, assessing potential risks and the impact of hygiene measures is important as a basis for evidence-based recommendations, to prevent adverse reactions from pet owners and to create guidelines for professionals regarding the handling and diagnosis of potentially infected animals.The project will collect important field data on the prevalence and significance of SARS-CoV-2 in a One Health aspect...",,2022,N/A,106401.81,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control,Animal source and routes of transmission | Disease surveillance & mapping | IPC at the human-animal interface,2021 +P30196,0142004449,National genomic SARS-CoV-2 surveillance programme,"During the Covid-19 pandemic, it was necessary to closely monitor the development and spread of circulating SARS-CoV-2 variants. Virus variants could influence the epidemiological situation, for example by being more contagious, causing more severe disease, evading immunity after infection or vaccination, or affecting the effectiveness of therapies. This subsidy enabled geographically and demographically representative genome sequencing of 2000 samples per week. This project was coordinated by the National Reference Center for Emerging Viral Infections (NAVI/CRIVE) at HUG. This monitoring made it possible to better assess the development of the pandemic and also served as a basis for decisions for targeted adaptation of measures.",,2022,N/A,16300628.01,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2021 +P30198,CYD-C-2021017,Early warning signals in OSINT,"Various sources of free information are available and list conflicts and demonstrations around the world. This information, in the form of time series, can provide indications and warnings about the development of a conflict. It is therefore interesting to try to find correlations and explanations from this data in order to be able to predict future conflicts. Electricity networks operate in operational modes that are increasingly different from the usual modes of recent decades. In addition to fundamental changes in production patterns, covid-19 is causing fundamental changes in consumption patterns. These will be marked in the coming years by great uncertainty and marked volatility. In addition, the pressure induced by cyberattacks on critical infrastructures does not ...",,-99,N/A,112576.01,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Secondary impacts of disease, response & control measures",Social impacts | Economic impacts,2021 +P30199,0142004471,"Genomic surveillance SARS-CoV2, preliminary phase","The course of the pandemic due to the Coronavirus SARS-CoV 2 is influenced by the virus strains in circulation. Certain strains may have decisive epidemiological characteristics such as greater contagiousness, cause more serious developments of the disease, reduce the effectiveness of a vaccine, etc. In December 2020, strains of the so-called English variant or Alpha variant began to be in circulation and suggested a more contagious strain. It was urgent to set up a genomic surveillance system by sequencing a certain number of coronavirus-positive samples. ETHZ, through the Science Task Force and Professor Stadler, have made their laboratories, resources and skills available for the implementation ...",,2021,N/A,1320632.57,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Not applicable,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2020 +P30201,0142004046,National Reference Centre for Influenza 2020-2022,"Influenza viruses can cause seasonal epidemics, but can also trigger pandemics. This is why flu is monitored in Switzerland through the voluntary Sentinella reporting system. However, flu-like illnesses can be caused by more than just influenza viruses, and there are also different types and subtypes of influenza with different virulence properties. For the timely monitoring of influenza and the timely, situation-appropriate adaptation of recommendations and measures to protect the population, additional information on circulating influenza viruses and their changes (antigenic drift, antigenic shift, development of resistance) is therefore important. Due to the Covid-19 pandemic, an additional goal is the virological monitoring of SARS-CoV-2 and other respiratory viruses. The goals of virological monitoring are: - Detection of influenza, SARS-CoV-2 and other respiratory viruses ...",,2022,N/A,1325996.52,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen morphology, shedding & natural history | Disease surveillance & mapping",2020 +P30202,7270295,Rapid Evaluation and Development of Cellular and Animal Tools to fight SARS-CoV-2,"Project funded by the SNSF: SNSF | P3 Research Database | Project 196062The coronavirus disease 2019 (COVID-19) pandemic has triggered an unprecedented health, economic and societal crisis in the modern world. The deployment of effective vaccines and cures against this disease requires that new models be developed to study their efficacy before they are used in patients.",,-99,N/A,325521.31,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics",Disease models,2020 +P30203,7270245,Characterization of the atypical M2 protein of bat influenza A viruses,"Project funded by the SNSF SNF | P3 research database | Project 189151The M2 protein is a small viral membrane protein that performs a variety of tasks in the replication cycle of influenza A viruses. The protein's conductivity for protons plays an important role in the introduction of the viral genome into the host cell. The cytoplasmic region of the protein, however, is important for virus maturation. This section of the M2 protein interacts with numerous cellular proteins whose role in virus maturation and release is still largely unclear.",,2023,N/A,524035.56,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P30205,20.008218,"Incidence, Spectrum of Symptoms and Risk Factors for Coronavirus Disease 2019 (COVID-19) among Healthcare Workers - a Prospective Cohort Study","This project will provide general insights into the epidemiology (including seroprevalence) of COVID-19 and SARS-CoV-2, as well as specific insights into the exposure and risk to healthcare workers. These findings are of utmost relevance for all hospitals in Switzerland, not least with regard to the deployment planning of healthcare workers.",,2021,N/A,359144.89,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,Epidemiological studies,Disease susceptibility | Disease surveillance & mapping,2020 +P30206,37379.1 IP-SBM,Bridging the gap in health associated influenza prevention programs (B-HAIP),Bridging the gap in health associated influenza prevention programs (B-HAIP),,2022,N/A,58176.8,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,,,2020 +P30207,1.20.02,Rapid identification and epidemiological analysis of OIE-notifiable viral animal diseases.,"Outbreaks caused by OIE-notifiable animal diseases, such as avian influenza virus (AIV), bluetongue virus (BTV) and African Swine Fever (ASF), can have severe socio-economic consequences [1-3]. This requires a prompt and adequate response by the governing body for effective animal disease control, which largely depends on the rapid acquirement of information regarding the identification and origin of such viral pathogens. The existing infrastructure within Switzerland is not equipped to provide such information within a matter of days and thereby might negatively influence the response time. The establishment of the state-of-the-art Oxford Nanopore sequencing technology in conjunction with a powerful bioinformatic-based data analytic pipeline that can be projected in a user-friendly visualization tool will considerably aid in the rapid identification and epidemiological understanding of important viral pathogens and will improve the outbreak response time [4,5].",,2021,N/A,235550.54,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Unspecified,Other | Unspecified,,,,,,,,Pandemic-prone influenza | Other,"State Secretariat for Education, Research, and Innovation SERI (Staatssekretariat für Bildung, Forschung und Innovation)",Switzerland,Europe,Unspecified,Unspecified,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2020 +P30243,10087890,"Clinical development of DIOS-HFVac3: A pre-clinically effective multivalent vaccine for Lassa fever virus, Marburg virus, and Sudan ebolavirus","DIOSynVax, a clinical-stage biotechnology company based in Cambridge, UK, is working on a groundbreaking project to develop a novel vaccine against four diseases which cause outbreaks of high consequence to human health including Ebola, Lassa, Marburg and mpox . The primary goal of our project is to protect populations in low and middle-income countries (LMICs), where the risk and impact of these epidemic diseases are highest. The DIOS-HFVac3 candidate vaccine delivers RNA- and codon optimised sequences encoding engineered antigens derived from 3 different viruses - the glycoproteins of Ebola- and Marburg virus and the nucleoprotein of lassaviruses - via a poxviral vaccine vector, shown to protect from mpox infection and/or disease. Our vaccine candidate has demonstrated (Fig 1, Appendix Q2) promising results in preclinical trials, demonstrating a robust immune response protecting relevant animal models from challenge with Ebola-Sudan, Marburg, and Lassa virus induced disease, making it a promising candidate in the fight against these important epidemic disease threats. This project will undertake five distinct work packages important to ensure that the clinical vaccine manufacturing process is performed at the very highest specifications to ensure that the vaccine meets all the regulatory and safety criteria prior to GMP manufacturing and in preparation for Phase 1 Clinical studies and future manufacturing scaleup. These include CMC management comprising the qualification of the seed material and technology transfer, engineering batch run for physicochemical stability analysis, confirmation of vaccine immunogenicity as well as formal toxicology study, and planning of a Phase 1 clinical study and eventually the generation of a business plan and technical case. Each of these work packages is designed to advance the DIOS-HFVac3 vaccine towards clinical trials and regulatory approval. This project is not just about creating a vaccine, but also about ensuring it can be produced and distributed effectively where it is most needed. We are working on manufacturing processes that will allow us to produce the vaccine at scale, including future manufacturing and subsequent advanced clinical testing in Africa. This project represents a significant step forward in the fight against epidemic diseases, leveraging cutting-edge technology, multidisciplinary expertise, and a proven track record in vaccine development, bringing our innovative vaccine candidate closer to clinical development, regulatory approval, and ultimately, implementation to protect people at greatest risk.",,2025,N/A,2223341.25,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Arenaviridae | Filoviridae | Poxviridae,,,,,,,,,Lassa fever | Ebola virus disease | Marburg virus disease | Mpox,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine logistics and supply chains and distribution strategies | Vaccine trial design and infrastructure,2023 +P30245,EP/Z001218/1,Nanofabrication of functional surfaces for durable antivirus,"Viral infections including COVID-19 and Monkeypox have led to drastic socioeconomic, educational, political, and cultural impacts worldwide. However, there is still a lack of effective methods for the rapid, broad-spectrum, sustainable control of the transmission of viruses through contaminated public facilities. This project develops new functional surfaces with rapid, broad-spectrum, sustainable antibacterial and antiviral properties based on a novel strategy that perfectly combines micro/nano-structural materials, Cu-bearing materials, and photocatalytic TiO2 materials. The genetic algorithm and finite element method will be used to optimize the designed functional surface. The controllable fabrication of the functional surface will be realized via laser interference cladding and hydrothermal technique, and the process parameter analysis and optimization will be conducted to improve the processing quality and achieve the controllable fabrication of the surface. Antibacterial and antiviral properties and regulation mechanisms of the functional surface will be demonstrated and analyzed. Self-cleaning and durability will be performed to verify the sustainable and long-term applications of the developed functional surface. This research will provide basic theoretical and key generic technical guidance for the development of new antibacterial and antiviral surfaces. This project will bring complementary expertise in optimal design, controllable fabrication, antibacterial and antiviral testing, and theoretical analysis. This combination has placed the team in the best position to achieve the ultimate objectives. The successful implementation of the proposed research will undoubtedly enrich the advanced knowledge, contribute important techniques, and enable the commercial exploitation and practical application of functional surfaces with rapid, broad-spectrum, sustainable antibacterial and antiviral properties to combat virus infectious diseases.",,2026,N/A,270481.55,Environment | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2024 +P30262,2907794,Inhibition of Zika Virus by hybrid interferons,"Zika Virus (ZIKV) is a re-emerging mosquito-borne flavivirus. In most cases ZIKV infection is mild and resolve on their own. However, ZIKV is also linked to developmental abnormalities in foetuses including microcephaly and other serious neurological diseases like Guillain-Barre syndrome in adults. Despite being declared an international health emergency, we have no specific treatment or vaccine available for ZIKV infection. Interferons (IFNs) are our bodies first line defence against viruses. Depending on their receptor usage IFNs are divided into three types, type 1, 2 and 3 IFNs. They control viral infection by inducing the expression of antiviral proteins that are encoded by interferon-stimulated genes (ISGs). The initial host response against virus infection is the induction of type 1 IFNs. There are 12 human IFN alpha (a type 1 IFN) subtypes but only IFNa 2a and 2b subtypes are used clinically. They have been approved by the FDA for the treatment of certain infections and cancers including chronic Hepatitis C, AIDS-related Kaposi sarcoma, hairy cell leukaemia, and hepatitis B in adults. However, studies have shown that IFNa 2 subtypes have weaker antiviral activity as compared to other more potent IFNa subtypes. For instance, IFNa 14 has been shown to be highly active against viruses including HIV and influenza A virus. Working with our industrial partner ILC Therapeutics, we have access to novel hybrid interferons alongside in-house synthetic and naturally occurring IFNa variants that are based on the IFNa 14 backbone. This study aims to test if the IFNa 14 and its derivatives have antiviral activity against ZIKV infection. To do this, we aim to test different IFNa subtypes and their synthetic derivatives for their inhibition of different lineage ZIKV utilising plaque assays, reporter assays and qPCRs. We will also aim to identify the different interferon stimulated genes (ISGs) that are differentially expressed in cells stimulated with different IFNa subtypes using RNA-Seq analysis and to validate the identified ISGs with qPCR and pulse SILAC proteomic analyses. This study will also generate ISG overexpression cell lines and knock-out cells lines to test for their sensitivity and resistance to ZIKV; and to determine the role of the ZIKV protein NS5 in counteracting the antiviral activity of the different IFNa subtypes. This will enable us to understand how hybrid interferons might control ZIKV infection and reveal the differences in therapeutic responsiveness according to viral genotype.",,2027,N/A,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Flaviviridae,,,,,,,,,Zika virus disease,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2023 +P30292,2890972,Advancing air microbiome research for the investigation of co-infections and for community use: a test case with SARS-CoV-2 and Aspergillus,"""New and re-emerging infectious diseases represent a critical threat to global public and animal health. Major viral outbreaks of, for example, Middle-Eastern Respiratory Syndrome (MERS), African Swine Fever, Swine and Avian Influenza, and SARS-CoV-2, alongside numerous bacterial and fungal infections and the rise in antimicrobial resistance, have all had major impacts on the human and animal population creating a substantial economic burden within affected countries. Indeed, the potential for zoonotic transmission of pathogens into the human population has emphasised the importance of an integrated ""One Health"" approach to pathogen surveillance across the human, animal and environmental nexus, with infectious disease monitoring programmes central to the protection of human, plant and animal populations. Researchers at Queen's University Belfast (QUB), the University of Glasgow and the University of Strathclyde have developed considerable expertise in the detection of pathogens from both environmental (e.g. wastewater) and clinical samples. Latterly research at QUB has expanded into the development of air sampling protocols for the monitoring of SARS-CoV-2 levels within the built environment. Although the detection and monitoring of pathogens on surfaces, and in both clinical and wastewater samples is relatively well advanced, their remains a need to develop better methodologies for community pathogen monitoring within air. By utilising the expertise within those research teams based at Queen's University Belfast (QUB), the University of Glasgow and the University of Strathclyde this project seeks to: 1). Assess the potential of air sampling as a tool to detect airborne pathogens (bacterial, fungal and viral) within a clinical setting using both culture-based and molecular (qPCR and metagenomics) approaches; 2). Determine the physical interaction between bacteria, virus particles and fungal conidia spores, and the impact of this on pathogen viability and detection via air sampling; 3). Investigate the impact of Aspergillus/SARS-CoV-2 and influenza co-infection on fungal/viral infection dynamics, inflammation, and cell death, using in vitro models of lung infection; 4). Using electrochemical biosensing technologies investigate if a biosensor (for SARS-CoV-2 initially) can be constructed and integrated with air sampling technologies, as a first step towards the development of a real-time air monitoring system for pathogens. Improving our ability to detect airborne pathogens alongside increasing our understanding of air-associated routes of infection, and the interactions between such pathogens, will ultimately lead to improvements in infection control measures within the hospital environment and beyond. """,,2027,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Infection prevention and control","Diagnostics | Environmental stability of pathogen | Disease surveillance & mapping | Disease pathogenesis | Barriers, PPE, environmental, animal and vector control measures",2023 +P30299,BB/X014266/1,"Pathogenesis, immunity, and control of coronaviruses in a large natural host animal, the pig","Coronaviruses have caused three epidemics of severe respiratory disease in humans since 2003, the last being the present COVID-19 pandemic. In each case the virus came from an animal species but was able to infect humans. In the first two epidemics, SARS and MERS, although the virus passed from an animal to humans, it did not pass readily from one human to another, limiting the size of the epidemic. SARS-CoV-2 on the other hand is readily transmitted between humans. Because the virus can mutate (change its genetic material), over time it can escape from the immune response, so that as in the case of influenza, repeated vaccination may be required to prevent severe disease, although so far the vaccines have failed to prevent virus transmission. Humans are in increasingly close contact with many animal species and the risk of further epidemics is therefore high. Pigs are one such species and can be infected with many coronaviruses including porcine respiratory coronavirus (PRCV), which causes a pneumonia similar to COVID-19. Like SARS-CoV-2 porcine coronaviruses can mutate, and recently more virulent viruses have emerged that cause economically important disease in pig herds. Pig coronaviruses have also been detected in some humans although as yet they do not appear to transmit between people. Because of the emergence of PRCV strains that cause economically important disease in pigs and because pig coronaviruses might jump to humans and cause another coronavirus epidemic, we wish to understand better how the virus infects cells in the respiratory tract, how the immune system reacts to the virus early in infection and how later on it either causes lung damage or protects against further infection. This information will be important for designing new ways to prevent or treat the disease both in pigs and humans. We will also test a novel vaccine platform which has the potential to induce very strong immune responses and possibly immune responses that could protect against widely different coronavirus. We have discovered PRCV strains that cause either severe lung disease (pneumonia) or very mild lung inflammation. We have also shown that those that cause severe disease multiply in the cells of the nose, windpipe and lungs, while those that cause mild inflammation multiply well only in the nose. Comparing the structure of these strains and making new strains by genetic manipulation will allow us to identify the parts of the virus that are important for virus entry into different cells in the respiratory tract. Part of these studies will be performed on cultured lung and tracheal (windpipe) tissues, minimising the use of live animals. To discover how the immune system responds to the virulent and innocuous viruses we will take tissues from animals infected with the two virus strains and analyse what genes are turned on one day and fourteen days after infection. This will tell us how the two virus strains programme the immune response and what sort of immune response develops after the early interaction of the viruses with the immune system. We will use a novel vaccine platform which allows the part of the virus that binds to cells (the receptor binding domain or RBD) to be displayed on a particle and internal proteins of the virus to be produced in the pig to ask several questions. First whether this vaccine induces strong and protective antibodies, second whether it can also induce protective T cells (the second protective arm of the immune response) and thirdly whether if both antibodies and T cells together are more protective than either alone. Finally using this system, we shall test whether displaying many different RBD in the vaccine induces antibodies that can protect against many different virus strains",,2026,N/A,918105.79,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Characterisation of vaccine-induced immunity",2023 +P30301,2452490,Proteome-level diversity in RNA viruses,"Studentship strategic priority area: Basic and Clinical Research Keywords: Influenza, Proteomics, Mass spectrometry, Mutation, Evolution Influenza viruses are major causes of respiratory disease globally with seasonal outbreaks responsible for hundreds of thousands of deaths worldwide every year. One of the main driving forces behind the success of influenza viruses is their capacity for mutation, brought about by high error rates in replication of the RNA genome. The effects of mutation in influenza virus genomes are compounded by errors in the transcription of viral mRNA, as this is performed by the same enzyme responsible for viral genome replication. Although mRNA mutations are not heritable, functional selection applies to the proteins they encode when they are translated, modified, trafficked and assembled into virions. As a result, mapping diversity in the pool of proteins in influenza virions can predict 'functionally permitted' mutations that could be a substrate for influenza virus evolution through natural selection. This project will initially make use of a novel workflow to re-analyse mass spectrometry proteomics datasets to assess protein diversity within influenza virions, 'deep sequencing the viral proteome.' We expect to identify the effects of both point mutations and internal deletions that arise from truncated viral mRNA. We will identify sites in viral proteins that tolerate or resist mutation, map these to viral protein structures in order to identify the potential effects of amino acid changes on protein structure and function. This proteome-level variation will be compared to genomic and transcriptomic data and to variation in existing influenza genome sequence data. As such, the plasticity of the viral proteome will be measured in relation to the viral genome, giving insight into where adaptation can be tolerated in viral proteins. We will then build on this assessment of mutational tolerance in influenza virus proteins. Using a combination of in silico prediction and molecular virology studies we will assess to the potential impact of protein heterogeneity on the immune response and on the development of therapeutic/vaccine targets for influenza viruses. We will also leverage our data to engineer functionally permitted tags into influenza viruses by reverse genetics, creating a platform for further molecular biology and imaging studies.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2020 +P30302,MR/V035789/1,MRC Transition Support Award CDA Edward Hutchinson,"This proposal is for Transition Support to continue the work of a Career Development Award (CDA), which was delayed and redirected in response to a number of unexpected issues. Both the CDA and the current proposal focus on influenza viruses. These cause seasonal influenza, which kills 290 000 - 650 000 people globally each year and is one of the leading global causes of death. As well as causing seasonal illnesses in humans each year, influenza viruses are unusually good at jumping from one species to another, as human and animal influenza viruses can exchange genes if they both infect the same host at the same time. The ready ability of influenza viruses to undergo this 'reassortment,' along with their high mutation rates, enables them to cause repeated and sometimes devastating pandemics. The work in the original CDA focused on proteins in the virus particles that transmit influenza infections. We showed that these were much more variable than was previously appreciated. The host cell and the virus can both strongly influence which proteins are included in virus particles and in what amount, and the proteins themselves can be modified in different ways. We also discovered an entirely new class of 'hidden' influenza virus proteins, and examined how the virus particles produced in natural influenza virus infections can vary in shape, from the spherical particles typically studied in the laboratory to enormously extended filaments. As our work developed, we were able to examine more sources of variation among influenza virus particles: in the genes they carry, in the proteins that make them infectious and the in shapes they adopt. This Transition Support proposal aims to consolidate this work. Work will begin by completing three well-advanced projects that were delayed during the CDA. The first of these draws together multiple lines of evidence to provide a picture of influenza virus particles in unprecedented detail, and showing where these microscopic structures can vary. The second shows how over time an infected cell alters the composition of the virus particles it sheds, making them more infectious just as the surrounding cells start to increase their antiviral defences. The third examines a set of chemical modifications to influenza virus proteins that can act like a series of switches, altering and regulating the proteins' functions. With this work, we will have completed a wide-ranging survey of the ways in which influenza virus particles can vary, and developed many novel tools to study this variation. We will then ask how knowing about the enormous scope for variation among influenza virus particles changes our understanding of what happens when we get infected with influenza. The ability of influenza viruses to swap genes inside their hosts shows us that virus particles can interact during an infection, but most of our understanding of how influenza viruses actually work focusses on understanding the initiation of an infection by one single virus particle. Once an infection is underway in a host, we know that large numbers of highly variable virus particles are shed into a small space and can interact, but we have not yet been able to examine how interactions within this 'viral microenvironment' shape the outcome of an infection. Using the tools we have developed, we will examine for the first time how the single influenza virus particle that infects us, rapidly creates within us a swarm of highly variable virus particles that interact to determine the course of our infection. As well as detailing the course of a normal infection, this will allow us to understand how the 'swarms' created by a human and animal virus could come together to seed the next respiratory virus pandemic.",,2023,N/A,599993.78,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P30303,MR/Y503459/1,ICF - Evaluate the potential of AstraZeneca's sialic acid tag technology for treating influenza viruses with Fc molecules,"Influenza A virus causes a highly contagious, acute, febrile respiratory illness that kills 250,000-500,000 people every year. The devasting effects of influenza are particularly felt in Africa. Current vaccination strategies face significant limitations, including that antibody and T cell responses wane quickly, mandating annual vaccination programs; it is immensely challenging to reliably predict which strains multivalent vaccines should target; and vaccine propagation must begin several months prior to each respiratory season. In the event of a pandemic, this delay between identification of a pandemic strain and mass rollout of vaccines will inevitably result in huge loss of life and disease burden. Since the lockdowns enforced during the Covid-19 pandemic, the epidemiology of influenza A virus has become even more unpredictable, as population level pre-existing immunity to influenza is lower than typical due to its interrupted circulation over two respiratory seasons. For these reasons, therapeutics are of critical importance as additional mitigations against influenza. Therapeutics are important additional mitigations against influenza. However, contemporary influenza-targeting antivirals, have significant limitations, including that they must be administered early to be efficacious and may select for resistance. Thus, there is an urgent need for additional therapeutic options. The Fc (fragment crystallizable) of human IgG has been administered safely to children in the treatment of idiopathic thrombocytopenia. We will therefore modify the Fc to be rich in a sugar called sialic acid, that interferes with the ability of viruses to bind cell surfaces, thereby preventing virus entry into the cell. Derived from antibodies, the Fc has many advantages that make it commercially appealing; including ease of manufacture in existing pipelines developed for IgG monoclonal antibodies (mAbs), favourable cost-of-goods profiles over larger mAbs, and proven safety and efficacy in children, that provide competitive advantage over other approaches that have yet to be approved for clinical use. By preventing, controlling, and treating influenza, our work addresses one of the overarching goals of the World Health Organisation Global Influenza Strategy 2019-2030, by providing an improved and more affordable alternative to traditional monoclonal antibodies or small compound molecules.",,2025,N/A,237694.5,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",,2024 +P30304,2887884,"Surveillance, detection, and environmental drivers of avian influenza-like viruses in African birds","Avian influenza is highly contagious, and if it spills over into human populations, could cause future influenza pandemics. When poultry are infected, the animals should be housed under strict biosecurity measures to prevent direct or indirect contact with wild birds. This project will assess how management of infectious diseases in poultry could impact conservation zones. More specifically, the spread and transmission patterns of avian influenza-like diseases that spill over from domestic animals, such as poultry, to populations of African penguins and other seabirds will be studied. In addition, an affordable and quick diagnostic test to test seabirds for the presence of avian influenza viruses will be develop. There is currently no diagnostic test available to survey seabird populations for avian influenza-like viruses. This will transform the management of disease outbreaks, policy development and enhance biodiversity conversation. The work will be divided into three Work Packages (WP), each resulting in at least one scientific paper/thesis chapter.",,2027,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Animal and environmental research and research on diseases vectors | Pathogen: natural history, transmission and diagnostics",Animal source and routes of transmission | Diagnostics,2023 +P30305,106007,Molecular Analysis of Surface Functionalization of Nanomaterials,"The influenza burden Each year more than 800'000 people in the UK see their GP for suspected influenza infection and 20'000-30'000 people are admitted to hospitals. Hospitals face the daily risk that incoming patients (110,000 annually in the Emergency Room in Addenbrooke's Hospital in Cambridge 2017/2018) will lead to Influenza outbreaks in the hospital. Indeed, there were more 2200 confirmed influenza outbreaks in the UK last year in hospitals, care homes, and schools. To prevent outbreaks, patients must be tested for influenza before antiviral treatment is initiated. Unfortunately, this testing process can take several hours, resulting in delayed diagnosis and treatment. The current established and trusted ""gold standard"" method of testing for influenza in hospitals can take up to 12 hours. A delay of half a day is highly costly to the patient and hospital: patients must wait longer to be seen by the correct department, wards become congested with patients waiting for test results and the risk of viral outbreaks increases as potential carriers of the virus wait for results. Clinicians have expressed a need for rapid influenza detection tests that can be carried out by non-medically trained personnell in the Emergency Room. A selection of currently existing rapid diagnostic tests (RDTs) has been tried. The sensitivity of most have been shown to be insufficient, thus often resulting in false negatives. There is an urgent need for a novel rapid diagnostic test for influenza virus that can be used in hospital emergency rooms. What can be done At HexagonFab, a biosensor has been developed and built from novel nanomaterials, which will bring the sensitivity of laboratory based tests to the emergency room. The technology gains its outstanding sensitivity through the unique surface of the nanomaterial, which is the core sensing element. In order to improve the sensor, it is necessary to investigate in detail how the nanomaterial interacts with its environment and how it can be tailored to be even more sensitive and specific. This continued InnovateUK A4I project brings the unique expertise of NPL, one of the leading research organisations of the UK, to investigate the surface of the nanomaterial and how the sensor can be optimised to achieve the sensitivity of current laboratory-based tests, while allowing use at the patient in the emergency room.",,2021,N/A,100096.03,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2020 +P30306,BB/X019780/1,22-ICRAD Call 2 Emerging porcine influenza and coronaviruses (EPICVIR),"Influenza and coronaviruses have caused some of the deadliest pandemics in humans, and swine are key viral reservoirs. Influenza viruses of type A and porcine respiratory coronavirus are enzootic in swine, but they differ in pathogenicity and immune control. Cattle are the natural host of influenza D virus, but it is now an emerging virus in swine, and its pathogenesis remains underexplored. Swine Influenza viruses of type A have enormous and still increasing genetic diversity with many ""reassortant"" (i.e. when genetic exchange occurs during co-infection involving different viruses or viral strains) genotypes circulating simultaneously, and is a proven zoonotic and pandemic threat. The pandemic potential of porcine respiratory coronavirus and swine Influenza D is uncertain. In this project, we aim to answer questions about the transmissibility and pathogenicity of these viruses. We aim to better understand what the transmission dynamics of these viruses are between swine and from swine to ferrets (which can be used as a model for humans). We also aim to study the immune response against these viruses, and what are the main factors that tip the balance to mild or severe disease. One of the main aims is to determine the zoonotic potential (i.e. the potential for these viruses to jump from a non-human animal to humans) of these viruses, and which ones in particular pose a higher risk. To do this, we aim to integrate data arising from different experiments by using relevant mathematical, computational and statistical techniques. Our results will help predict the zoonotic potential, transmission, and pathogenicity of existing and emerging swine Influenza viruses and porcine respiratory coronaviruses.",,2026,N/A,597788.59,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease pathogenesis",2023 +P30307,BB/W009404/1,"Seals: a natural experiment in cross-species transmission, adaptation and pathogenicity of influenza A virus","Today, we can painfully appreciate that infectious diseases from animals pose a substantial threat to human life and society. As we continue to grapple with COVID-19, experts agree that a new influenza pandemic remains a matter of 'when', not 'if'. Our ability to prevent and respond to future pandemics depends on identifying all potential sources of influenza that could spill over into humans and designing new treatments and vaccines. The biggest source of threat are livestock - poultry and pigs; these are extensively monitored and studied by global research networks already. However, an epidemic can also arise from a less expected and understood place, and seals are a prime candidate. There are three reasons why we need to study influenza in seals. First, grey seals are likely one of the largest least well-understood mammalian reservoirs of influenza, which pose a threat to both humans and wildlife. This is especially important now because grey seals in the UK are seeing an unprecedented level of population growth. Second, unlike livestock, influenza spreads freely in wild populations of grey seals without any human intervention. This offers a unique natural experiment, from which we can learn how influenza adapts to mammals over time. This will enhance our ability to predict the source and nature of future pandemics generally. Third, there are strong indications that grey seals manage to co-exist with influenza without adverse effects, while closely related harbour seals are known to suffer mass mortality events where thousands die. A comparative study of the different seal species can uncover drivers of the difference and lead us to new disease interventions. In my study, I will use swab and blood samples from wild grey and harbour seals in Scotland collected by SMRU (Sea Mammal Research Unit) at the University of St Andrews. I will also use samples from stranded seals taken to wildlife rescue centres run by the RSPCA (Royal Society for Prevention of Cruelty to Animals) and the UK government's APHA (Animal and Plant Health Agency). My aims are to understand the dynamics of influenza infections in seal populations and to identify the host factors that drive differences in disease severity. At Oxford, I will analyse the samples with cutting-edge sequencing technologies and computational biology, along with molecular methods to study wild animal biology in the lab. The project will establish a UK-wide network of collaborators from universities, specialist institutions, charities, and government agencies to address fundamental questions in biology with implications for human and wildlife health.",,2025,N/A,504096.77,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30308,MR/X000117/1,Orchestrating resident memory B cell responses in the lung during secondary infection with influenza virus,"Respiratory infections present major threat for human health. Among those, influenza virus represents a significant medical challenge, inducing over 3 million cases of severe illness and 500,000 deaths per annum. Moreover, the highly mutable nature of this virus continues to raise concerns of a potential deadly outbreak. Pioneering studies carried out more than 100 years ago demonstrated the enormous potential of pre-existing antibodies for preventing the disease. These early works demonstrated that transfer of antibodies from immunized animals into naïve hosts protects them from lethal doses of influenza strains. Importantly, the most effective results were obtained when the antibodies were administrated directly into the airways of the lungs, where viral replication takes place. These and subsequent studies not only established the potential of antibodies to provide immunity against influenza, but also demonstrated the importance of antibodies being localised to sites of infection as a major factor in achieving optimal results. Better understanding of mechanisms that increase antibody titres locally within the lung may therefore help to guide the development of new and more effective vaccine strategies to prevent the spread of influenza variants. Here we aim to explore a unique subset of memory B cells that has been discovered a few years ago to develop within the lungs of mice and humans following infection with influenza virus. These cells were named resident memory B (BRM) cells because they remain confined to the lung tissue, likely indicating a specialized role in protecting this organ. To study this newly identified memory B cell subset, our lab developed novel mouse models and advanced live imaging approaches that allow us to visualize BRM cell behaviour directly within their natural environment, in live lungs of influenza infected mice. Using these methods, we discovered that upon secondary infection, BRM cells are quickly recruited to sites of infection and subsequently differentiate into antibody producing plasma cells within regions where viral replication takes place. These findings uncover a new mechanism that enables rapid and highly localized secretion of antibodies directly within infected sites in the lung. In this proposal, we aim to identify the molecular mechanisms that regulate this process. We will ask how BRM cells successfully navigate towards infected sites within the lung, how they differentiate into antibody producing cells in these regions and how they contribute to the establishment of short- and long-term humoral immunity against influenza virus. We anticipate that these studies will help to develop new vaccines against influenza and, possibly, other pulmonary pathogens. Moreover, since in some cases antibodies can also cause diseases (e.g., in the case of some autoimmune diseases, allergies or cancer), our findings may help to guide the development of novel therapies aiming to prevent antibody production in the context of immunological disorders.",,2026,N/A,808426.48,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2022 +P30309,2445844,Novel autophgy pathways for the control of influenza virus infection,"The recent outbreaks of avian influenza and the threat of a human influenza pandemic has highlighted the need to understand prevention and control of this virus by developing effective antiviral therapies. We have recently shown that influenza virus activates a novel autophagy pathway called LC3-associated phagoytosis (LAP). We have developed a unique animal model defective in this pathway, and this project will investigate host innate immune responses after this pathway has been compromised. Aberrant host defence leading to inflammatory disease may account for some of the pathological changes seen in this disease. Respiratory virus infections are of global significance to both the human and animal populations.",,2024,N/A,,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2020 +P30310,10020318,In vivo animal demonstration of a novel RNAi-based prophylaxis to fight influenza,"Globally, seasonal influenza is responsible for 290,000-650,000 deaths/year. In England, despite a well-developed vaccination and surveillance programme, flu kills 7,000-22,000 people/year. The flu vaccine works better in some years than others. Across all age groups including children, flu vaccines prevented 15-52% of flu cases between 2015-2020\. Secondary care costs associated with influenza-related hospitalisations in England account for £99.5-£128million/year, and 285,000-400,000 bed days/year, with average 7-9 days hospitalisation. Influenza patients requiring intensive care face a high mortality rate of c20%. Over the last century, influenza has caused three pandemics, killing tens of millions of people. Resultant UK productivity losses arising from influenza are significant: costing £28.9million/year in sick days and £270million/year in human capital costs arising from premature mortality. Vaccination is the main weapon against influenza but faces significant challenges: **Poor efficacy:** Flu viruses rapidly and constantly mutate. Vaccines are prepared a year in advance by predicting predominant strains in the upcoming flu season. Overall efficacy of 45% reported for flu vaccine in the US in 2019/20, while efficacy as low as 25% was reported in England in 2017/18\. Latter resulted from poor match by vaccine to one of predominant strain's (Flu A-H3N2) antigen. Immune senescent or immunocompromised groups may not develop a full antibody response to the flu vaccine; thus, are likely to experience even lower efficacy. **Poor coverage:** Even in the UK, with relatively high vaccination rates, flu vaccination rates last met WHO target: 75% vaccination rate amongst people aged 65+years in 2005/06, since then hovering around 70.5-74.1%. **Threat:** Currently only 3 haemagglutinin (HA) and 2 neuraminidase (NA) viral protein variants have been detected in humans. In birds, pigs, and other hosts, 18-HA and 11-NA protein variants have been detected, providing an enormous reservoir for antigenic shifts that could trigger pandemic outbreaks. Based in the Cancer Research UK Cambridge Institute, Eleven Therapeutics is developing game-changing RNAi therapeutics to deliver highly effective and broad-spectrum siRNA molecules against multiple disparate flu strains. In this project, we will validate the efficacy of our intranasal RNA-based cocktail by conducting airborne flu virus transmission experiments in a large-animal (pig) model. Our prophylaxis will be suitable for self-administration in the form of a nasal spray, stable at standard fridge temperatures. Our innovative approach is highly complementary to flu vaccination programmes and directly addresses both coverage and efficacy challenges, with potential to significantly reduce social and economic impacts of seasonal influenza and improve pandemic preparedness.",,2023,N/A,457273.1,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Prophylactic use of treatments,2022 +P30311,2761529,The interactome of the influenza A virus polymerase in replication,"The aim of this work is to identify host factors specifically involved in IAV replication. As influenza virus is able to rapidly adapt to overcome therapeutics that target viral proteins, host factors act as good targets for the development of anti-influenza drugs. Consequently, this work may suggest new therapeutic targets to treat influenza virus infection, while aiding our understanding of IAV replication and the host determinants of viral pathogenicity. In turn, the tools developed in this work may also be used to further understand host determinants of IAV species specificity. Given the mechanistic differences between transcription and replication and the existence of host factors that are specifically supportive of replication (such as ANP32), we hypothesise that additional host factors exist that are for replication only.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Disease pathogenesis",2021 +P30313,EP/Z001242/1,Lung-gut axis: Inter-organ Communication during Acute Respiratory Infection,"Influenza virus infection is one of the most common respiratory diseases. Symptoms of influenza include fever, cough, stuffy nose, body aches, headache, and fatigue. Additionally, patients may experience gastrointestinal symptoms such as nausea, vomiting, and diarrhoea. Yet, the reason for these clinical signs is still not clear. During acute respiratory infection, immune cells release inflammatory mediators at the site of infection that activate peripheral nerves extremities and lead to brain activation, without migration of the virus into the brain. Brain activation induces in return an anti-inflammatory response mediated by peripheral nerves which release neurotransmitters and neuropeptides dampening the immune response in the lungs. Interestingly, these pathways are not lung privileged, but also innervate other organs such as the gastro-intestinal tract. Within the intestine, the enteric nervous system (ENS) is a complex network of neurons and glia that controls many digestive functions (contraction/relaxation of the intestine, enzymes secretion). Although the ENS can function independently from the brain, these two organs are interconnected by neuronal fibers and together coordinate the intestinal physiology. I thereby hypothesize that peripheral nerves' activation during influenza virus infection could be responsible for the observed gastrointestinal symptoms. In my project, I will test this hypothesis using a mouse model of influenza virus infection. I will implement multiscale and cutting-edge technologies in neuroscience to be able to register, identify and manipulate neurons in different organs. This analysis will help understanding the mechanisms underlying the multi-organ symptoms observed during acute respiratory infection and its impact on neuronal circuits at the level of the whole organism.",,2026,N/A,262123.84,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis,2024 +P30314,2596826,Characterisation of the antiviral properties and mechanism of action of natural product MM 46115,"The influenza A virus is a major cause of severe respiratory infection, which results in 20,000 hospitalisations per year in the UK. Vaccines have been developed against the virus to prevent severe infections, but vaccine hesitancy limits their utility. Antiviral drugs are administered to hospitalised patients to prevent replication of the virus. However, the virus has managed to evolve resistance to these drugs, rendering them ineffective. Therefore, there is a pressing need for new and effective treatments. Actinomadura pelletieri, a bacterium that causes mycetoma, has been reported to produce MM 46115, a spirotetronate polyketide active against multiple viruses, including influenza A. MM 46115 may have the potential to be developed into a novel treatment that overcomes resistance to currently used antiviral drugs. Previous work has shown that treating influenza infected cells with MM 46115 can reduce cell death without toxic side effects. While the planar structure of MM 46115 has been determined, its relative and absolute stereochemistry remains to be fully elucidated. This is required to develop a better understanding of its structural similarity to other spirotetronate polyketides and begin illuminating the structure-activity relationship. This project aims to further investigate the antiviral activity of MM 46115 against influenza A using plaque assays, RT-PCR and immunofluorescence. The stereochemistry of MM 46115 will be elucidated using a combination of predictive sequence analysis of biosynthetic enzymes, 2D NMR spectroscopy, CD spectroscopy, X-ray crystallography, and micro electron diffraction. Proteomics will also be used to identify protein targets for MM 46115. Finally, a better understanding of MM46115 biosynthesis will be developed, enabling bioengineering approaches to the production of structural analogues that inform the structure-activity relationship to be employed.",,2025,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",,2021 +P30315,2623123,Cambridge ESRC DTP Interdisciplinary Studentship 2021: Early-life and intergenerational effects on later-life outcomes over the long-term,"My proposed research will explore two main themes, using the two data sources mentioned in the project description. Firstly, I hope to use the detailed Derbyshire Health Visitor records to study the short- and long-term impact of the 1918/1919 influenza epidemic on infants during gestation and the first year of life. I want to identify the general impact of influenza on both pregnant mothers and the infants themselves, and how the timing of the influenza-onset may have impacted its effect. I hope this study can add to the 'positive selection' debate regarding shocks in utero. I will also use the dataset to look at the relationship between infant mortality and the foetal origins thesis. Secondly, I will use the Cambridge Group Family Reconstitution dataset to study infant mortality clustering in England, and intergenerational fertility and mortality rates. Through these ideas, I hope to expand our understanding of the mechanisms through which infant mortality is propagated individually and across populations, and how in utero environments are impacted by exogenous factors. I am particularly interested in how the causes behind health inequality and infant mortality manifest themselves biologically over time, and how to break these cycles.",,2025,N/A,,Human Populations,Unspecified,Adults (18 and older) | Infants (1 month to 1 year),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Orthomyxoviridae,H1,H1N1,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis,2021 +P30317,10033054,AIRA: AI-based Research Assistant for Active Site Structure and Dynamics from Energy Landscapes,"This project integrates computational and experimental approaches in a new cloud platform that provides access to state-of-the-art energy landscapes tools and AI-based assistance for biomolecular design and drug discovery. It brings together Dodrotu Limited, the Wales group at the University of Cambridge, and the Schnell group at the University of Oxford, to deliver an energy landscapes AI-based solution for discovery and analysis of influenza drug-binding sites and epitopes and explanation and characterisation of binding mechanisms, formulated in a way that allows for experimental validation with NMR and rapid prototyping of designs. Dodrotu is a UK information technology services startup established in 2019 and incubated at Oxford University Innovation. Dodrotu has developed a secure, end-to-end encrypted platform for delivery of applications that augment traditional communications with AI. The founders of Dodrotu were members of the Wales Group and have expertise in optimisation, machine learning, signal and natural language processing, artificial neural networks, functional programming, VoIP and mobile technologies. Professor David J. Wales is Chair of the Theory Group in the Chemistry Department at Cambridge University. He has developed new theory and computational methods for exploring energy landscapes in molecular and condensed matter science, which have been recognised by named lectures, visiting professorships, and awards in the UK and overseas, including election to the Royal Society in 2016\. Professor Jason R. Schnell is a group-leader in Oxford University's Department of Biochemistry and an expert in protein structure and dynamics. His group recently advanced our understanding of influenza, and has detailed knowledge of high entropy regions and mechanisms of polymerisation and membrane binding of Influenza A virus M1 protein. Our ambition is to provide new tools that will both greatly speed up drug discovery and lower its costs. After validation on influenza as part of this project, the new methodology will find a wide range of applications in molecular science, from small molecule targeting of key proteins in health and disease, to protein design for protein therapeutics and industrial enzymes.",,2023,N/A,217853.06,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P30318,2433640,Impact of variation in equine influenza A virus pathogenicity determinants on vaccine effectiveness and interspecies transmission,"Influenza A viruses (IAV) are believed to have circulated in horses for centuries and to have crossed species barriers to infect humans in the past. In 2005, the first evidence for transmission of equine influenza A virus (eqIAV) to dogs was reported; the virus subsequently became endemic in the USA. We retrospectively demonstrated that eqIAV had also jumped from horses to foxhounds in the UK in 2002, but did not become established. Experimental infection of ponies with an eqIAV strain isolated in 2003 confirmed the more severe clinical signs seen (including prolonged coughing) than with earlier isolates. This was associated with greater induction of pro-inflammatory cytokines. Genome sequencing of the 2003 strain revealed a truncation in the viral NS1 protein, which modulates the host cell cytokine response. Using reverse genetics to switch the NS gene segment, we confirmed that the truncated NS1 induced a greater cytokine response in infected cells. This suggests that the species jump occurred due to emergence of an eqIAV strain with increased pathogenicity. Interestingly, the NS1 truncation was lost on adaptation to dogs. Vaccines against eqIAV have been available since the late 1960s and vaccination of UK racehorses has been compulsory since 1982. There is a process for updating vaccine strains but there continue to be periodic major epidemics of equine influenza - these have occurred in 1963, 1979, 1989, 2003 and 2019. These major epidemics are usually associated with some deaths among unvaccinated horses. Variation in the haemagglutinin surface glycoprotein as a cause of vaccine breakdown has been extensively studied. The aim of this project is to investigate the role of variation in viral proteins that determine the pathogenicity of IAV in vaccine breakdown and interspecies transmission. Reverse genetics is a technique where a recombinant influenza virus can be generated by transfecting eight plasmids each encoding one of the eight viral gene segments into mammalian cells in vitro. This allows specific changes between viruses to be studied individually, for example by swapping only the gene segment encoding NS1 on an 'isogenic' background. This technique will be complemented by bioinformatics analysis to compare the genes that determine the pathogenicity of IAV in epidemic eqIAV strains with inter-epidemic strains. The ability of viruses in which genes have been swapped or mutated to replicate and induce or resist pro-inflammatory cytokine responses will be tested in cell culture. The use of established techniques and involvement of collaborators with complementary skills should ensure any challenges can be addressed and the appropriate risk assessment for this work is already in place. Identification of patterns associated with the emergence of an epidemic strain could improve the ability of the World Organization for Animal Health (OIE) Expert Surveillance Panel to pre-empt the next equine influenza epidemic.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2020 +P30319,2721869,Interaction of SARS-COV2 and influenza virus with particulate matter air pollution,"Patients infected with influenza and SARS-CoV-2 are more than twice as likely to die as someone with SARS-CoV-2 alone (Stowe J, 2020) There is evidence of higher transmission rates and worsening of health outcomes when subjects are also exposed to high levels of ambient particulate matter (PM) pollution (Lu, 2020). As documented with the COVID-19 pandemic, evidence from Lombardy, Italy, suggested that higher ambient levels and daily fluctuations of pollution, increase the rate of COVID-19 infection (Setti L, 2020). SARS-CoV-2 has been detected indirectly on PM in pollution via RNA extraction and polymerase chain reaction (PCR) (Setti L et al, 2020). Viable SARS-CoV-2 virus (detected by PCR and positive culture) has been shown in the ultrafine fraction of PM with diameters of 250-500 nm (Lednicky JA, 2021), raising the possibility that these particles could act as a vector for SARS-CoV-2, but there is no direct visual evidence as to whether these particles form hybrids. If PM and the respiratory viruses interact in air, the resulting particle-hybrid could affect airborne spread, transmission and infectivity. On the other hand specific components of PM are redox active and there is very recent evidence that diesel PM can deactivate influenza viruses (Hsiao TC, 2021). This PhD will test the hypothesis that PM acts as a vector for SARS-CoV-2 and influenza viruses, increasing the potential for airborne spread of the virus, infectivity and for boosting cellular inflammatory response. In addition, it will establish whether influenza or SARS-COV-2 interact with specific components of PM and whether specific PM chemistries amplify or protect against cellular damage. The outcomes will provide guidance around which polluted microenvironments are potentially most unsafe for infection and could shed light on new therapeutic interventions. Task 1 will optimise infection and PM dosing of human epithelial cells. Task 2 will determine response of human nasal epithelial cells Human Nasal Airway Epithelial Cells (HNE) to SARS-CoV-2-infected and PM. Task 3 will assess whether SARS-CoV2 adheres to PM in the cellular environment. EPSRC areas: particle technology and biophysics",,2026,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2022 +P30320,10077113,Innovative nasal vaccines to prevent pathogen colonization and infection in the upper respiratory tract,"Bacterial and viral respiratory infections are a leading cause of morbidity and mortality worldwide. Streptococcus pneumoniae and Bordetella pertussis, influenza virus and SARS-CoV-2, are responsible for diseases with major public health impact: communityacquired pneumonia, whooping cough, influenza and COVID-19, respectively. Vaccines against some of these diseases, administered by intramuscular or subcutaneous injection, do not prevent colonization or infection of the upper respiratory tract (URT), and therefore have limited impact on pathogen transmission. The NOSEVAC consortium aims to develop and assess innovative nasal vaccine platforms as a novel concept to block the earliest stage of infection, thereby inhibiting URT colonisation, transmission and disease. The project builds on a unique consortium of 12 renowned and complementary teams from the EU, UK and Switzerland. NOSEVAC's objectives are to: • Develop vaccine formulations for nasal delivery of RNA- and protein-based antigens • Discover bacterial antigens that promote colonization of the URT • Use a combination of in vitro and in vivo models for optimal evaluation of vaccines efficacy • Identify key host immune factors required for long-term protection of the URT in human • Deliver two nasal vaccine candidates to fight S. pneumoniae and B. pertussis infection, and a single bivalent vaccine to prevent influenza and COVID-19 • Address acceptability of nasal vaccination Expected outcomes include (1) strengthening innovation in Europe by enriching the pipeline for novel vaccines against (new) respiratory infections, (2) increasing knowledge on the mechanisms underlying URT colonization, infection and immunity, and (3) evaluating nasal vaccine acceptability by stakeholders. NOSEVAC will develop strategic research avenues to fight respiratory pathogens including those with epidemic potential and will facilitate evidence-based decision making to policy makers and investors.",,2028,N/A,1716334.99,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,"Vaccines research, development and implementation | Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P30321,2443757,The Anti-Viral Role and Therapeutic Potential of Novel Seaweed-Derived Compounds,"Objectives: Influenza viruses are segmented single stranded negative sense RNA (-ssRNA) viruses in the Orthomyxoviridae family and cause respiratory infections. Influenza A viruses (IAV) are responsible for the majority of human disease and 5 pandemics since 1889, the most recent of which was 2009 and the most lethal in 1918 with over 50 million recorded deaths worldwide. Vaccines and antiviral drugs are available however these are often ineffective due to rapid virus evolution. Methods: This study focuses on an Enriched seaweed extracts (ESE) isolated from the brown seaweed Ascophyllum Nodosum by the industrial partner Byotrol. ESE was screened for antiviral activity by plaque reduction assays against IAV H1N1, H3N2 subtypes and rhinovirus (RV), which was used as a non-enveloped model to test for broad-acting activity. Time of addition assays, immunofluorescent imaging and FACs analysis were used to help determine the mode of action. The therapeutic potential of the ESE was then explored using differentiated human bronchiole epithelial cells at the air liquid interphase and in a murine model challenged with IAV. Results: The data indicates ESE primarily interacts directly with virions, preventing virus cell binding and internalisation. Interestingly, ESE also inhibits early and late stage of the influenza lifecycle when treatment occurs after cell binding, which was not seen with rhinovirus. This inhibitory effect appears to prevent trafficking of viral RNPs to the cell nucleus and release of progeny virus by targeting neuraminidase activity. Intranasal administration of ESE in mice infected with IAV or at the time of infection reduced viral load in lung tissue. Discussion: ESE may be a promising broad acting antiviral agent in the treatment or prophylactic treatment of respiratory infections through the inhibition of virus cell binding and internalisation.",,2024,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H1 | H3,H1N1,,H3N2,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2020 +P30322,2435420,Predicting the Evolution of Influenza,"Much of the burden of infectious disease today is caused by antigenically variable pathogens that can escape from immunity induced by prior infection or vaccination. Influenza viruses are classic examples of such pathogens and also unique in that an extensive worldwide surveillance network exists that routinely tracks both the genetic and antigenic evolution of the virus, analyzing ~20,000 strains each year. Further many aspects of the virus are relatively easy to work with in the laboratory making it an excellent model system for studying such antigenically variable pathogens. Recent advances in my laboratory have resulted in computational an experimental methods that can, to some degree, predict the evolution of the virus. Despite all of this, the governing evolutionary processes governing this evolution are not understood, and experimental work on what we think is the key protein involved in this evolution, at the level of detail that appears necessary, is beyond current experimental techniques. The goal of this PhD project is to study this detail using computational approaches. In particular, to address a fundamental issue in the data that are used as the basis for all of this work. Sam has worked with us as an undergraduate looking at this topic and has made important insights that look highly likely to substantially improve the basic measurements used in understanding and predicting the evolution of influenza viruses. This is a tremendously exciting prospect. Sam will have real-time access to the genetic and antigenic data on the 20,000 strains of influenza virus collected worldwide each year, and the experimental data generate by our wet-lab collaborations--these data will form the foundation on which to test hypotheses and predictions that this project will generate.",,2024,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P30323,BB/X016137/1,Modelling to inform interventions during Highly Pathogenic Avian Influenza outbreaks in Great Britain,"Avian influenza is a highly contagious disease, affecting both wild birds and domestic poultry. The poultry industry suffers substantial economic losses due to this disease, both in Great Britain (GB) and around the world. The 2021-22 outbreak in GB has been the largest in the country's history, and seasonal outbreaks are expected to continue to occur. Mathematical models are increasingly used during outbreaks of a range of diseases to inform future scenarios and to guide control measures. This project involves developing a national-scale mathematical model of avian influenza transmission around GB, in collaboration with the UK Government's Animal and Plant Health Agency (APHA). It builds on our previous work with APHA during the 2021-22 outbreak, in which we spent six weeks developing a preliminary transmission model to project future spread of the virus and to guide control interventions. In the current project, we will build on our previous rapid-response research, taking advantage of the longer timescale of this project to develop a flexible modelling framework with a high level of rigour. This includes fitting the parameters of the transmission model to a range of data sources, and accounting for both transmission between poultry premises within GB and importations of infection from elsewhere. By working closely with APHA, we will ensure that the model can be run on APHA computer systems, permitting its use by policy advisors to guide interventions in future outbreaks. Once we have developed the transmission model, we will use it to explore the effectiveness of a range of different control interventions that could be applied during future outbreaks in GB. A benefit of our collaboration with APHA is that we are in a position to use the model to test practical strategies that could be deployed effectively. We will also develop a user-friendly software tool and Graphical User Interface based on the model, allowing the user to change model parameters themselves and test different control interventions without requiring specialist knowledge about the computing code. To encourage others to use the software, we will run an outbreak simulation exercise in which we will provide simulated outbreak data to policy advisors, who will then use the tool to determine optimal interventions. Similar exercises have been conducted before for a range of other livestock diseases. This exercise will be conducted at the start of the third year of this project, enabling any feedback to be incorporated into the model and software tool. We will also run a two-day workshop for other researchers in which we describe the modelling framework and software tool, and demonstrate their use. In summary, this project will involve the development of a national epidemiological modelling resource that can be used to plan control measures during future avian influenza outbreaks in GB. It complements existing research on avian influenza by providing a tool that will be used by policy advisors for the foreseeable future to determine optimal interventions during outbreaks.",,2027,N/A,904084.92,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other | Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping,2024 +P30324,MR/T028769/1,MRC AMED - The HDAC6/USP7 axis in enveloped RNA viral infection,"Influenza A virus (IAV) causes annual epidemics and occasional pandemics with continuous threat of emerging and potentially lethal strains derived from reassortment with avian or swine IAV. In addition to development of a universal influenza vaccine, a deeper understanding of cell biology of IAV infections is needed to discover antiviral strategies that target cellular proteins and pathways. Viral uncoating is an early step in infection that is poorly understood, but we think that the host cell factors involved can be targeted effectively as an antiviral strategy. IAV entry and uncoating is well-studied compared to many enveloped RNA viruses. Uncoating requires a ubiquitin-mediated, misfolded protein degradation pathway known as aggresome processing. Here, the key host player, the cytosolic histone deacetylase 6 (HDAC6), senses misfolded protein 'tags' and activates a cellular pathway that helps to break apart the viral shell during entry. In this study we will address the interplay between HDAC6 and ubiquitin-modifying enzymes, and target multiple host factors to block viral uncoating and thus block infectivity. Our findings may contribute to the understanding of general viral uncoating pathways and lead to conceptualisation of a broad spectrum antiviral that can combat emerging and re-emerging viruses of medical importance.",,2022,N/A,99676.46,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P30325,MR/Y004337/1,Evolutionarily smart vaccine strain selection for proactive vaccinology,"For viruses, such as SARS-CoV-2, that can change over time to escape immunity, keeping a vaccine up to date, and effective against current variants is a substantial challenge. Circulating viruses are constantly changing and are thus a moving target, that is easy for the variants in the vaccine to fall behind. Before SARS-CoV-2, the only vaccine for which the variants in the vaccine are routinely updated to track the evolution of the virus is the influenza virus vaccine. For influenza, decades of research and practice have resulted in a WHO assessment and strain recommendation system that functions well, but can still be substantially improved. The equivalent system to influenza vaccine strain selection for SARS-CoV-2 is still in its infancy. Our consortium will build directly on the partners' expertise in both influenza and SARS-CoV-2 to optimize the SARS-CoV-2 vaccine strain selection process to best protect the UK population that is at risk and will continue to be vaccinated against COVID. This project builds on the vaccination strategy outlined in our advisory paper to the UK Government SAGE committee titled 'Setting up medium-and long-term vaccine strain selection and immunity management for SARS-CoV-2'. To achieve our goals it is necessary to be able to accurately determine 'antigenic' differences among SARS-CoV-2 variants. Antigenic differences are the changes in the virus that result in escape from immunity raised by earlier vaccination or infection. We will test SARS-CoV-2 variants from the UK and around the world to generate, and keep current throughout the project, 'antigenic maps' to determine, at high resolution, the antigenic relationships among SARS-CoV-2 variants. Further, we will horizon-scan and proactively explore how the virus might further evolve using a combination of three methods. 1. Surveillance of UK and global variation in collaboration with the UK Health Security Agency project partner and colleagues world-wide involved in surveillance including the US Centers for Disease Control and US National Institutes of Health. 2. Identifying genetic changes in the virus that reveal early signs of being advantageous by analyzing patterns of parallel evolution in the global sequence surveillance data. 3. Generating in the laboratory variants of the spike protein of the virus (not live virus) with which we experimentally test the antigenic and characteristics of amino acid substitutions ahead of the current evolution. In combination with this virological surveillance we will also do 'serological surveillance' in which we track the antibody immunity in a cohort of 800 individuals for which we have highly reliable vaccination and infection history from the start of the pandemic and will continue to track during this project. This serological surveillance will allow us to both measure the selection pressure on the virus to escape immunity, and to estimate the population immunity to new variants that might evolve, and thus determine which variants the current population has least immunity to, and thus to which it is most at-risk. We will then test alternate vaccine strain selection choices to find those that best build immunity in the part of antigenic space that most needs it. There is substantial optimization that can be done here because such vaccination is being done in the context of prior immunity to earlier variants. We will thus select and test vaccine strains using a combination computational models, animal models, and in final stages experimental medicine in humans. This work will be tightly integrated with, and contribute substantially to, the related european, US, and WHO global vaccine strain selection processes.",,2028,N/A,10900063.27,Human Populations | Viruses,Unspecified | Not applicable,Unspecified | Not Applicable,Unspecified,Unspecified | Not applicable,Unspecified | Not applicable,Clinical | Non-Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Vaccines research, development and implementation","Pathogen genomics, mutations and adaptations | Immunity | Disease surveillance & mapping | Vaccine design and administration | Vaccine trial design and infrastructure",2024 +P30326,NE/Y001591/1,ECOFLU : Understanding the ecology of Highly Pathogenic Avian Influenza in wild bird populations,"Wildlife populations naturally experience a wide range of infections and disease. Understanding how they circulate in the environment, how they are evolving over time and how different hosts are affected is key to understanding both their impact on different animal species and their potential to spill-over into domesticated animals and humans. We are currently experiencing a major outbreak of Avian Influenza that is having a major impact both on wild birds and commercial poultry at a global scale. This is a disease caused by infection by a group of Influenza A type viruses of which water birds are the natural host. These viruses usually circulate in wild waterfowl and shorebirds with relatively little impact. However, the past year has seen a significant change in the impact of one particular subtype of avian influenza called H5N1. Mortality reports in wild birds have been highest in seabirds with over 200,000 dead birds reported over a three month period in Scotland alone. These are novel hosts that up until this point have been relatively unaffected so we currently lack information about how this disease is impacting in these novel host populations, hindering our ability to make informed decisions about any potential mitigation strategies that might be put in place or evaluate their likely success. In this project we have three main objectives. Firstly, we will track the evolution of the virus over time and space across a range of different host species. This will tell us about possible routes of transmission but also help us track how the virus is changing as it evolves and to identify any viral changes that may alter its pathogenicity or its ability to jump between species. Secondly, we will focus on the hosts and explore what proportion of birds are exposed and survive infection. We will do this in populations that have been monitored over many years so their individual life-histories, age, and migration routes are known to help us identify which whether particular parts of the population may be more vulnerable or more important in transmission. Finally we will use the data we are collecting to create a modelling framework that represents the wider population of different species to test how resilient different populations might be to this disease and to use as a tool to evaluate and prioritize potential mitigations that can be put in place to minimise any impact on host populations and limit future disease spread.",,2026,N/A,1053358.94,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures",2024 +P30327,BB/V004697/1,YY-EEID US-UK The evolutionary ecology of pathogen emergence via cross-species transmission in the avian-equine influenza system,"Viral emergence poses a constant threat to humans and animals and we are neither able to predict which viruses will emerge, nor where, when, or which populations will be affected. The overall aim of this project is to determine how environmental, host, and virus factors influence host-pathogen interactions and transmission dynamics of potentially emerging viruses. Avian influenza viruses (AIVs) provide unique opportunities to address this because they have jumped into humans, dogs, pigs and horses, with significant consequences on public health, food security, and the global economy. We will focus on the transmission and emergence of AIVs to horses because AIV strains have emerged in horse populations on independent occasions. We propose to perform field work in a well-defined ecosystem that favours avian-to-horse AIV transmission and also to perform laboratory experiments using avian and equine influenza viruses with different levels of ""equine fitness"" - ability to infect and transmit in horses. Our laboratory experiments will use genetic engineering to capture changes in fitness due to virus evolution. Results obtained will be combined in a mathematical framework that will enable the estimation of risk of viral emergence, including the effects of herd immunity. This multidisciplinary research will provide new insights on the mechanisms that underpin viral emergence and will aid the design of more effective intervention measures to control future events of viral emergence.",,2025,N/A,1183356.39,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +P30328,10050739,"Determining customer benefits of reduced influenza and norovirus transmission, using sewage surveillance","Untap is tackling one of the greatest challenges of our time, keeping our communities safe from viruses and infections. Currently viruses are only detected when an individual presents symptoms. Often, this is after viral transmission has already occurred. Influenza and norovirus were estimated to cost the UK economy 4% productivity loss in 2019; accounting for £ billions in lost revenue, and millions of infected individuals. Sewage surveillance is an incredible tool. It is used to measure the health of a community directly by their collective sewage. Humans shed viral RNA from day zero of infection, therefore this can be used to detect viruses pre-symptoms, and pre-transmission. Unlike lateral flow tests, which often have low participation rates, wastewater can provide broad coverage. However, the current state-of-the-art is manually collecting the sewage and analysing it in a laboratory. This analysis takes days, and costs up to £ thousands per sample. The cost and delay to the data has prevented sewage surveillance being carried out at a local scale. Untap have developed a prototype to detect COVID-19 in sewage of a community: onsite, automated, sewage surveillance. In this project we will develop this prototype to detect influenza and norovirus. This prototype will then be deployed long term at two sites, integrating the viral data into their day-to-day workflow. This will enable us to determine the customer benefits, both economic and intangible.",,2024,N/A,59971.9,Viruses | Environment,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease surveillance & mapping,2023 +P30331,2748405,Suppression of T cell immunity and antibody production during virus infection and sepsis,"The generation of protective antibodies against infection is dependent on ""help"" from CD4+ T follicular helper (TFH) cells which are elicited in response to bacteria and viruses, such as influenza and SARS CoV-2. However, these cells can decline when immune responses are over- exaggerated (sepsis). The student will use immunological techniques and innovative gene profiling strategies to examine why low numbers of CD4+ TFH cells correlate with poor outcome in sepsis",,2026,N/A,,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2022 +P30332,BB/V002821/1,Genomic epidemiology of equine influenza virus in the United Kingdom,"The horse industry and its associated industries make a substantial contribution to the UK economy. Therefore, not only do equine infectious diseases pose a serious risk to horses, but also have the potential to significantly affect the National economy. Equine influenza (EI) is arguably the most important infectious disease of the horse (in economic terms). EI is endemic in the UK and many other countries around the world and is caused by equine influenza virus (EIV). As with other influenza viruses, EIV can acquire mutations in its genome and evade host immunity induced by vaccination. However, epidemiological information has shown that in the UK, EI affects mainly unvaccinated animals. Vaccination against EI is compulsory for competition horses. In 2019 the UK experienced one of the largest EI epidemics in history: over 200 outbreaks spread throughout all four Nations were reported. An important feature of this epidemic is that 26 of the outbreaks were reported among vaccinated horses. This led to a six-day closure of all horse competitions, causing significant economic losses. While the total losses incurred by the cancellation of equestrian events is currently unknown (but likely to have run into millions of pounds), the Horserace Betting Levy Board has confirmed that the betting levy alone (i.e. the tax raised on bets) that was lost was £1.5M over the 6 days. As the 2019 EIV epidemic was finally contained, we can use it to learn valuable insight to prevent and control future epidemics. Current advances in sequencing technologies allow us to characterise the entire EIV genome directly from a nasal swab obtained from a sick horse. In turn, virus genetic information, if linked with epidemiological data, can be used to track the spread of viral diseases in time and space. We propose to combine genetic information with epidemiological data to reconstruct the spread of EIV during the 2019 epidemic, identify the most likely origin of the epizootic virus, and determine the patterns of genetic change of EIV during the epidemic. To this end, we will sequence nearly 400 virus genomes, most of them from the 2019 UK epidemic, as well as viruses from other countries to put the epidemic in a global context. This is a joint project between the Centre for Virus Research (CVR) and the Animal Health Trust (AHT). The CVR is a National Centre for Virology and has extensive expertise in virus sequencing and sequence analyses. The AHT is the reference laboratory for EI and hosts Equiflunet, a UK-wide equine surveillance network specifically designed to monitor EI. Results from this project will help inform the design of improved intervention measures to prevent and control future EIV epidemics.",,2024,N/A,549965.67,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2021 +P30333,2402163,Adapting influenza predictive models to model previously unknown infectious diseases.,"The goal of the project is be to investigate to what extent is it possible to adapt an influenza-like-illnesses (ILI) model that makes predictions based on Google search frequencies to other infectious diseases on the example of COVID-19. The scope would also include verifying what data sources could enhance the performance of the source model and the transfer pipeline, as well as investigating how to enable the models to account for the increased online search activity caused by the public's concern about a disease.",,2024,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,,2020 +P30334,2414134,Influenza A virus evolution: Determining the key factors that influence emergence of influenza variants of animal and public health significance,"Our research aims to understand the complex evolutionary pathways that result in the emergence of influenza virus variants that pose a threat to human and animal health. The project will identify viral and host factors (particularly in poultry and pigs) which determine the potential for emergence into new hosts and explore how this understanding can be used to implement effective control measures such as vaccination. We take an inter-disciplinary approach to One Health questions, by integrating surveillance, virology, ecology, and state-of-the-art antigenic and genetic computational analyses to understand pathogen evolution. Along with training and guidance, you will have flexibility to shape the project according to your interests.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen genomics, mutations and adaptations",2020 +P30335,2763179,Synthesis of antiviral natural products and derivatives,"The project will develop novel natural product-derived antiviral molecules to treat viral diseases such as SARS-Cov-2 (COVID-19) and influenza A (Seasonal flu). This timely and exciting project is a collaboration between researchers based in the Schools of Chemistry, Veterinary Medicine & Science and Pharmacy at University of Nottingham. This project will provide experience of multi-step synthetic organic chemistry and its application to the synthesis of biologically active molecules and/or natural products. New molecules will be tested for biological activity by our project partners, and the leading compounds will be selected for further development into a new class antiviral drugs.",,2026,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Novel Pathogen,,,,,,,,,COVID-19 | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P30336,BB/V001868/1,High-throughput single-molecule analysis of the influenza A genome structure and assembly,"The influenza (flu) virus is the microscopic pathogen that causes flu in humans and animals. We propose to use special microscopy methods to understand the structure of the genetic material of the flu virus, and how interactions between the genetic material can become important in flu pandemics. The genetic material, or genome, of the flu virus is made of RNA (a long chain of molecules that encodes genetic information) and is divided into eight individual segments. The natural host of the flu virus is wild birds; however, in a process called 'reassortment', different strains of the virus can swap RNA segments in a way that allows us to infect other host organisms, including humans. Reassortment events result in the generation of entirely new virus strains, to which humans have never previously been exposed. When there is no existing immunity in the human population to a novel influenza virus, reassortment can cause deadly worldwide pandemics, such as the Spanish flu pandemic in 1918, which was responsible for over 50 million deaths worldwide, and the 'swine flu' pandemic in 2009. Whilst H5N1 'bird flu' strains haven't yet reassorted to the extent that they can reliably infect humans and cause a pandemic, outbreaks in birds have been devastating for the poultry industry since millions of birds have been culled to reduce virus spread, resulting in huge economic losses. Despite flu being one of the best-studied viruses, we are still unsure how exactly the genomic segments contact each other inside virus particles. Much of our knowledge of this process has relied on data obtained using methods that measure the properties of millions of molecules (or particles) in one go, and therefore report on the averaged properties of all of the molecules. We plan to use advanced 'single-molecule techniques', which allow us to study one molecule (or particle) at a time; this allows us to see details unique to each molecule (or particle) that may be impossible to see using traditional analytical or biological methods. We plan to perform our single-molecule analysis by using many small pieces of fluorescent DNA, that will bind all the way along the virus gene segments, to detect the presence and map the structure of the gene segments at very high resolution. Further, the fluorescent DNAs will not be able to bind to sections of the genome that interact with other genomic segments (as these areas will not be accessible due to the close contacts between segments), thereby allowing us to build up a picture of crucial RNA-RNA interactions within virus particles. To image the virus particles as they are being detected by the small DNA pieces, we will use a specialised ""single-molecule fluorescence"" microscope, which is carefully designed to allow the detection and monitoring of individual fluorescent molecules present in a detection zone (as opposed to conventional microscopes that require thousands or millions of molecules to be present in a detection zone). We anticipate that our research will help the scientific community to better understand how the genome segments of the flu virus interact and cause pandemics, and help in efforts to control and stop its spread. Our discoveries should also help us understand and control other viruses that cause danger to humans and animals, and contribute towards development of new diagnostic tests for rapid and sensitive detection of influenza and other pathogenic viruses.",,2023,N/A,587832.83,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P30337,2601332,Synthetic glycolipids to investigate the interactome of viral glycan-binding proteins,"Pandemic RNA-based viruses such as SARS-CoV2 and influenza A strains are associated with a varying mutational burden to evade attack by components of the adaptive immune system. Their often rapidly evolving nature has made these viruses challenging targets for vaccine development: influenza vaccines have to be updated annually, and new SARS-CoV2 strains with impaired efficacy of neutralizing antisera are emerging. Being produced by human host cells, these viruses are highly glycosylated on Asn-Xaa-Ser/Thr sequons (e.g. 22 for SARS-Cov2 Spike). Addition or ablation of glycosylation sites is considerably slower than the antigenic drift of peptide sequences, with some glycans being essential for virus entry. Given that a large part of the surface of viral glycoproteins is covered by glycans, glycopeptides are likely to be important targets for antibody recognition. For instance, a neutralizing antibody recognizing a conserved glycopeptide epitope on coronaviruses including SARS-CoV2 was found serendipidously by cryo-electron microscopy. The epitope occupies a large 300 Å2 surface but crucially relies on the presence of the glycan. However, the field is currently lacking diagnostic technologies to profile immune responses against defined glycopeptides simply because these probes are much less straightforward to synthesise and immobilize than non-glycosylated peptides. At the same time, assessing the capability of sera from infected or vaccinated individuals to neutralise infection relies on cumbersome, low-throughput cell culture experiments. We hypothesise that antibodies against viral glycopeptides play a crucial role for neutralisation. This project will leverage the potential of synthetic glycopeptides to develop targeted diagnostics that profile the neutralising capacity of patient sera against respiratory viruses, with SARS-CoV2 as a case study. We will develop a method to append photo-switchable lipid tags to synthetic glycans. Photoswitches will be designed to enable binding experiments by glycan microarray analysis. This physical sciences innovation will allow us to cover a large structural space, as different orientations of glycans can be probed. Thereby, our data will feed into the generation of diagnostic devices and optimized vaccine antigens that should be much more resistant towards antigenic drift than pure peptide epitopes.",,2025,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2021 +P30338,BB/V019872/1,21 ICRAD Future rodent management for pig and poultry health (RodentGate),"Apart from consuming and spoiling animal feed, and damaging infrastructure in and around farm buildings, rodents are a considerable threat to animal health and One Health. They can cause direct stress on pigs and poultry but are mainly important as carriers of pathogens. These include economically very significant diseases like Swine dysentery, Aujeszky's Disease, PCV2 and Encephalomyocarditis. Wild brown rats can carry Influenza A and might act as an intermediate for the transmission of avian influenza between wild birds and poultry. For some other diseases like African Swine Fever, rodents may act as mechanical reservoirs or they may support ticks that can carry ASF. Rodents also play a role in the epidemiology of leptospirosis and salmonellosis or in spreading antibiotic resistant bacterial strains such as livestock-associated MRSA. They can pick up the infection from infected pigs or poultry and spread it within and between farms, they can act as a bridge between wild fauna and livestock, and they can maintain the infection locally when a farm is emptied and decontaminated after a disease outbreak or livestock turnover. Thus, there are very good reasons for rodent management on pig and poultry farms. An important approach has always been the use of rodenticides. However, concerns about the environmental safety of the most common rodenticides has led to changes in the European and national regulations that restrict their use and pose new challenges for efficient rodent management on farms. There is also the problem of resistance against these poisons. This project RODENTGATE will investigate the rodent-related risks for animal health in the pig and poultry industry and how this might change with altered rodent control. Ecologically-based rodent management is a strategy that combines an Integrated Pest Management approach with a thorough knowledge of the rodent ecology, enabling interventions to be precisely targeted in time and space, whilst being ecologically and economically sustainable. This requires a very good understanding of the rodent demography, life history, space use, dispersal capacities as well appropriate documentation of pathogen presence and transmission patterns in the rodent population. Proper understanding of transmission mechanisms is crucial since killing hosts may have unexpected effects on the spreading of an infection.",,2024,N/A,637076.88,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2021 +P30339,BB/V011286/1,[YY-EEID US-UK XXXX] Predictive phylogenetics for evolutionary and transmission dynamics of newly emerging avian influenza viruses,"Influenza virus is a global problem, causing widespread harm to human health and the food production system because it also infects chickens and pigs. Vaccination is difficult because of the variety and changeability of flu strains found in nature - primarily in wild birds, where often they cause little harm. However, when these strains of virus spill over into domestic poultry or humans, they can cause massive economic losses and fatal disease respectively. In the last twenty years, this has been graphically illustrated by the H5N1 and H7N9 outbreaks. Global surveillance programmes track the virus' movement and as part of this, characterise the sequence of the viral genome. Some aspects of virus behaviour can be accurately predicted from these sequences. However, many other important aspects of virus biology, such as whether it will travel across continents, which species it will infect and whether it will cause serious harm, are much harder to forecast. Our premise is that the volume of sequencing data now available, along with recent advances in computational methods of using such data, will make it possible for the first time to generate virtual models of how the virus will evolve under specific circumstances and how these viral variants will behave. Such models have the potential to produce risk estimates of new strains as they arise that can be used to inform policy and direct strategies to head off impending threats. To achieve this goal, we have brought together a team of international experts with interdisciplinary expertise in mathematical modelling, influenza surveillance and biology, and the infectious disease-public and animal health interface. Importantly, this includes colleagues from China, the likely epicentre of the virus. Together, we will create the computer models that can understand and forecast virus evolution; models that will be made accurate and then tested through a series of focussed laboratory experiments designed to produce the needed data, and whose types of output will be tailored to the needs of end users through a series of workshops that include the primary stake holders so they can inform the scientists on what information they need.",,2025,N/A,1736791.51,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | H7 | Other,,,,H5N1,,H7N9,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies","Pathogen genomics, mutations and adaptations | Disease transmission dynamics | Disease surveillance & mapping",2021 +P30340,MC_PC_21021,Tackling Emerging Co-Infections,"Humans are continuously exposed to multiple pathogens yet, with the exception of a few well defined coinfection scenarios (HIV and tuberculosis for example), relatively little is known about the impact of co-infections on morbidity and mortality. There is growing evidence indicating that co-infections are common, exacerbate disease severity and can considerably worsen outcome (Influenza or COVID-19 associated Aspergillus infection for example). Co-infections with drug-resistant pathogens have shown to add another layer of complexity with high case-fatality rates. Our aim is to integrate and exploit the expertise of four Centres that are tackling the major pathogen groups [viruses, bacteria, fungi and parasites] to promote UK-wide research on the pathophysiological impact and mechanistic basis of disease in co-infections.",,2024,N/A,271421.38,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Clinical,Unspecified,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,Severe Acute Respiratory Syndrome (SARS) | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,"Disease pathogenesis | Supportive care, processes of care and management",2022 +P30342,MC_UU_00034/1,From proteins to virus particles: the structure and function of virions,"Structural biology aims to understand how the shapes of the molecules of life, such as viral proteins, direct their functions. This is achieved by experimental determination of the 3D shape of biological molecules at the level of their individual atoms. Atomic structures can be combined with mathematical models of how molecules might move (molecular dynamics) and how they might evolve to evade host defences. Understanding the structure, dynamics and evolution of viral proteins can give researchers new ways to think about viral infections which can be tested in the laboratory. In this programme we will bring together expertise in structural biology (Bhella, Carter), molecular dynamics (Grove), mathematical modelling (Illingworth) and molecular and compositional biology (Hutchinson) to study the structure and function of virus particles (virions) of influenza viruses, coronaviruses and respiratory syncytial virus.",,2028,N/A,6848791.04,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2023 +P30343,MR/X001598/1,Innate interferons in epithelial defence against respiratory viruses,"Respiratory viruses are a major threat to human health and economic prosperity. Examples include influenza and the virus that causes coronavirus disease 19 (COVID-19), SARS-CoV-2. In order to develop medical interventions to combat these viruses, we need to better understand the normal immune response to viral infection in target cells, such as the cells that line the airways - the air passages of the lung. Through the careful study of patients with unusually severe COVID-19, it appears that certain immune factors play an important role in limiting disease at the earliest stages of infection in the airway. These factors are known as 'interferons'. Interferons are produced by virally infected cells. They signal uninfected neighbours to adopt an 'antiviral state' that blocks viral spread. Two major types of interferons are made by airway cells, type I and type III interferons. Consequently, viruses have evolved several strategies to evade this response. Type I and III interferons are distinct factors but share similar mechanisms of action. However, little is known about their individual functions or how they interact in humans. Understanding this will tell us how best to manipulate individual interferon types for clinical benefit. Our study of human patients with rare 'spelling errors' in their DNA (mutations) that affect the interferon pathways teach us valuable lessons. Patients with mutations of the type I interferon system are vulnerable to severe COVID-19, suggesting that type I interferons play an essential role in protecting against serious consequences of viral infection. Interestingly, these individuals cope normally with most other respiratory viruses, such as influenza, as do those with specific lesions of the type III interferon system. However, patients with impairment of both type I and III interferon systems can develop severe disease due to many respiratory viruses. Based on these observations, I propose that type I and III interferons compensate for one another in the defence of the airway, but that in some cases there are gaps that viruses such as SARS-CoV-2 exploit. I will use new cutting-edge laboratory models. We make use of stem cells that, in theory, are able to turn into any other type cell type in the human body. We have developed a way to turn them into cells that line the airway. We expose them to air, matching what happens in the airway. We then infect airway cells with different viruses, including SARS-CoV-2 - which causes COVID-19 - and influenza. We will measure the growth of the viruses and the damage that they cause to the airway cells. The reason for using stem cells to create these airway cells is that we can introduce 'spelling errors' into the DNA of the stem cell, preventing them from responding to interferons. By comparing the behaviour of the virus in these different airway cells, we will learn which interferons are important in controlling specific viruses. We will also measure the immune response to these viruses using techniques to measure the responses of individual cells. This will help us to identify the way that interferons work and allow us to do more detailed experiments to confirm our findings. We will also investigate the impact of specialised immune cells, present normally in the airway, on this process. We think that they will aid the interferon response of airway cells. Finally, we will conduct experiments in a rodent model of viral infection to assess how these interferons operate in the airway in the intact organism. Together, these results will explain how these immune factors work and give insight into the purpose of these apparently independent systems. It is possible that this is a deliberate strategy by the host to mitigate against viral evasion of interferons, or it may be that they work together, or are individually better against certain viruses. This information is relevant to the clinical use of interferons to treat or prevent viral disease.",,2028,N/A,2182377.51,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Pathogen: natural history, transmission and diagnostics","Disease pathogenesis | Supportive care, processes of care and management | Immunity",2023 +P30344,BB/W003295/1,Development of novel broad-spectrum antiviral compounds for use in animals and humans,"The current pandemic highlights the need for effective antivirals to treat active infections, in conjunction with vaccines, to prevent infection. We recently made an important discovery of a highly effective broad-spectrum antiviral thapsigargin (TG), a specific inhibitor of the Ca2+ pump located on the cellular organelle endoplasmic reticulum (ER), that could be a game changer in the treatment of major human respiratory viruses: coronavirus (including SARS-CoV-2 that causes COVID-19), influenza virus and respiratory syncytial virus (RSV). TG's host-centred mechanism of action, as opposed to conventional direct acting antivirals, reduces the likelihood of drug resistant mutants emerging, a distinct advantage for treating highly mutable RNA viruses. Coronavirus, influenza virus, and RSV are also global pathogens of animals (including cattle, pigs and poultry). Antiviral development for livestock lags behind its human counterpart, despite its potential benefits of safeguarding animal health and productivity. Given that future pandemics are likely to be of animal origin, where animal to human (zoonotic) and reverse zoonotic (human to animal) spread take place, antivirals, such as TG and its derivatives, could play a key role in the treatment and control of important viral infections in both humans and animals. Thus, our goal in this proposal is to enhance the impact and commercial significance of TG through the generation of novel secondary derivatives with greater antiviral potency for animal and human use. We have established that TG is orally active as an antiviral, and that it is converted into a limited number of ester hydrolysis and side chain oxidation metabolites. We hypothesise that one or more of such TG metabolites are novel structures with enhanced antiviral activity. To this end, we propose to carry out detailed in vivo pharmacokinetics (PK) analyses of TG to fully determine its metabolites post-absorption, synthesise the main metabolites identified, and characterise the synthesised metabolites for antiviral activities to generate comprehensive cellular PK and antiviral data of the most promising TG derivative(s) for clinical development and commercial exploitation. TG and its derivatives represent a whole new generation of powerful host-centred antivirals (as opposed to conventional antiviral drugs that directly target viruses) that could be adopted in a holistic ""One Health"" approach to control human and animal viruses. The outcomes of this project could have far-reaching impact on a global scale in the treatment and control of RNA viral infections of human and animal importance.",,2024,N/A,829888.5,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2022 +P30347,2444832,Regulation of the integrated stress response to viral infection by RNA modifications,"State primary research question and where appropriate the primary hypotheses being tested The hypothesis is that the m6A modifications have a role in the dynamic regulation of cellular and viral gene expression in the context of the integrated stress response and other antiviral pathways. The aim is to explore this hypothesis by generating human lung cell lines that are depleted in m6A writers, readers or erasers in combination with infection with influenza A virus or SARS-CoV-2. Importantly, these respiratory viruses have different replication strategies and interactions with the host cell. Viral replication in the context of modulating the m6A system and mutations in the viruses that sensitise them to the innate immune system will be analysed. The most robust phenotypes will be subjected to an unbiased (genome-wide) profiling of mRNA expression and translation with the outcomes functionally validated.",,2024,N/A,,Viruses | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2020 +P30349,BB/X020045/1,22-ICRAD Call 2 - Emerging porcine influenza and coronaviruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2026,N/A,148844.57,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Clinical characterisation and management","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease pathogenesis",2023 +P30350,BB/V019899/1,21-ICRAD Virulent Non-Notifiable Avian Influenza; Determinants of virulence of emerging viruses,"Europe is one of the world's largest poultry meat and egg producers and exporter of poultry products. Disease outbreaks are a major threat for the poultry industry. Avian Influenza (AI) is listed as a top challenge and with that, is a major concern of the European and worldwide poultry industry. In poultry, the severity of AI virus (AIV) strains is classified into Highly Pathogenic (HPAI) or Low Pathogenic (LPAI). HPAI strains cause severe infections and high levels of mortality. HPAI and LPAI of the H5 and H7 types are notifiable diseases, i.e. diseases that are required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. European Member states conduct surveillance programmes and outbreaks involving AI H5 and H7 subtypes are notifiable to the OIE. However, not only LPAI H5 and H7 and HPAI subtypes form a threat for the poultry industry. Several of the non H5/H7 subtypes such as H3 and H9, can be very virulent and infections with these strains can also cause severe production losses. Besides the economic consequences, these virulent non-notifiable LPAI (nn-LPAI) subtypes have a major impact on animal welfare by causing severe clinical symptoms, high mortality rates and - in case of controlling the outbreak - culling of diseased and/or healthy flocks. AI is a zoonotic disease and past influenza pandemics were caused by viruses that were at least partly derived from AI viruses. Therefore, impacts on public health may be great if nn-LPAI with high zoonotic potential are not controlled adequately. The FluNuance consortium aims to develop a diagnostic tool or identification system for virulent nn-LPAI strains. To achieve this we will first have to understand why these normally low pathogenic viruses become more pathogenic and how they interact with their hosts, chickens and representatives of wildlife: mallard, geese and pigeon. This knowledge will allow us to better assess the potential risks that viruses from the animal reservoir imposes for the poultry industry and vice versa. As a consequence, poultry production will be threatened less by these viruses, thereby reducing negative impacts on animal welfare and decreasing the numbers of flocks that are culled. In case the emerging nn-LPAI has high zoonotic potential, the risk of a pandemic will be lowered. Thus, this proposal addresses the ever-increasing importance of the poultry industry and aligns with the consumers' demands for 'healthy food from healthy animals'.",,2024,N/A,562903.73,Animals | Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Unspecified,Non-Clinical,,Orthomyxoviridae,H3 | Other,,,Unspecified,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Diagnostics | Pathogen genomics, mutations and adaptations | Animal source and routes of transmission",2021 +P30352,2884251,"The Biopolitics of Industrial Chicken: Accumulation, Health and Disease in Capitalist Poultry Production","The Covid-19 pandemic has shown again that human and nonhuman lives are always already bound together within what we call the 'social' (Haraway, 2008). Recognition of this constitutive relationality has driven recent 'more-than-human' developments across various disciplines including sociology that have sought to challenge entrenched dualistic categories. This research aims to contribute to this growing research area through a critical examination of the 'poultry' industry, biosecurity discourse and zoonoses. Each year, at least 75 billion birds are killed within the poultry industry (FAOSTAT, 2022). It has been suggested that intensive rearing/slaughter of poultry contributes to the emergence and evolution of zoonotic pathogens such as avian influenza, Salmonella, Campylobacter, E. Coli, and antibiotic resistance. The 'imminent' threat of an Influenza A pandemic and wide-range antimicrobial resistance mean that these pathogens are dangers to public health. The industry's response to outbreaks has been to propagate a discourse of biosecurity based on scientific knowledge ('poultry 3 science'), with an emphasis on the 'freeness from disease' of industrial operations. This discourse can be observed within the guides and advertisements of poultry companies/associations and even reports provided by the FAO (2013). It has been accompanied by a range of biotechnological 'fixes', including intensive confinement, use of antibiotics, and automated slaughter employed for both efficiency and putative sanitary gains. Yet biosecurity in poultry science is contested and ambiguous, a space where differing knowledge claims are struggled over and enacted. This research will trace this ambiguity in order to explore the ontological-epistemic politics of biosecurity discourse and associated knowledge-practices in the poultry industry. It will critically examine whether/how the industry is able to partially enrol or co-opt science, and to what extent and by what means it is able to influence knowledge-making and gain public support through its self- representations. Inseparable from this is the capitalist nature of the industry. In conversation with the growing literature on 'animal capital' (Shukin, 2009), this research will therefore also probe the specific value of birds to poultry capital and how their appropriation for accumulation is linked to human labour. It will trace how the practices of the industry incorporate birds into more-than-human circuits of value, asking how in turn do these practices figure in the biosecurity discourse. Modifying Bennett et al. (2018)'s provocative points about the global biomass of broiler chickens being a definitive marker of the 'Anthropocene', I will ask how 'poultry' can instead be problematised as a 'marker species' of the 'Capitalocene' (Moore, 2016).",,2027,N/A,,Animals | Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Farmers | Other,Non-Clinical,,Orthomyxoviridae | Novel Pathogen | Other,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Policy research and interventions,2023 +P30353,NC/X002349/1,Developing a next generation in vitro 3D immune organoids system for studying vaccine-induced immune response and immune-ageing across the life-course,"Vaccination is the most effective protection against infectious diseases, which relies on vaccine-induced immunity. All new vaccines need to be thoroughly tested for their protective immunity before their clinical use in humans. From the initial selection of vaccine candidates to pre-clinical testing of new vaccines for immunogenicity, it typically involves the use of a large number of animals. There is a great need for non-animal, laboratory-based methods to evaluate vaccine-induced immune responses including antibody response. We aim to develop an in vitro assay system that mimics human immune system and able to detect vaccine-induced immune responses, and therefore has the potential to replace or reduce the use of animals in vaccine testing. This may include the selection of vaccine candidates and batch testing, and mechanistic studies including immune ageing in humans. Vaccine-induced immunity against infection critically depend on adaptive immune system involving T and B cell activation and antibody response. The effects of ageing on immunity, including vaccine-induced immune responses, are also typically manifested in dysregulated function of T and B cells and antibody response. It is known ageing is generally associated with increased susceptibility to severe infection, including COVID-19 and influenza. An in vitro system enabling the cellular and molecular mechanistic studies on immune ageing, particularly at the early stage of immune senescence (i.e. the timing/age period it occurs) would have a big impact on understanding immune ageing to inform strategies against severe infection, and would help to reduce animal studies. Vaccine-induced immunity is typically tested by measurement of T cell response and antibody production which is produced in the secondary lymphoid tissues such as lymph nodes. Structurally similar to lymph nodes, adenoids and tonsils are lymphoid tissues located in the upper airway (nasopharynx), named nasopharynx-associated lymphoid tissue (NALT) and known to be the induction site for immunity against respiratory tract pathogens. We previously studied and demonstrated marked T cell and antibody responses in NALT immune cells of children and adults to a number of antigens and vaccines derived from some airway pathogens such as influenza. We therefore hypothesize that tonsillar immune cells could be used as a laboratory system to test vaccines, which will have an enormous potential to replace or reduce large numbers of animal experiments. In this project, we propose to take advantage of the availability of tonsillar tissues from routine elective surgery, to develop a lab method in test tube vaccine-induced immune responses. In collaboration with an industry partner with specific expertise in lab systems helping cell growth in 3D, we will use tonsillar cells to develop a next generation, animal-free cell culture system for testing vaccines, and also be able to study effect of aging on immunity in humans.",,2024,N/A,244612.34,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,"National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) | UK Research and Innovation (UKRI)",United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2023 +P30354,BB/T013087/1,Development of next generation vaccine technology inducing rapid and strong immunity through targeted delivery of antigens to chicken immune cells,"Safe and disease-free poultry production systems are crucial for maintaining food supplies to feed the increasing human population and to improve the livelihoods of farming communities. However, the biggest threat in the sustainable growth of farmed animal production is the emergence, re-emergence and continual prevalence of a multitude of infectious animal pathogens, such as avian influenza. Primarily, the control against these pathogens is achieved through vaccination. However, the effectiveness of most of the current vaccines is suboptimal, where they may only reduce manifestation of clinical disease and mortality, but infected animals continue to shed viruses resulting in a continual chain of infections to susceptible naïve and vaccinated animals. For example, despite the large-scale deployment of multiple doses of influenza vaccine to an individual bird, manifestation of disease continues in the form of endemic prevalence and farmers continue to bear debilitating losses with up to 100 percent flock mortality or loss of egg production along with the threat of zoonotic infections. Therefore, improvement of the current vaccines are required that produce stronger immunity and full protection against disease, together with a reduction in shedding of infectious virus from infected animals, preventing the endemic prevalence of these viruses in farmed animals. In this proposal, we plan to develop robust and effective vaccines that elicit strong and durable humoral and cellular immune responses against viral pathogens which cause severe economic losses in poultry industries. As a proof-of-principle, we have demonstrated that targeted delivery of antigens to chicken immune cells potentiate the antigen-specific immune responses in vaccinated chickens compared to the untargeted counterpart or the conventional killed virus vaccines. The targeted vaccines demonstrated a significantly faster and a significantly higher immune response. These studies therefore provided strong data to take this new vaccine technology from laboratory to the farm. To achieve this goal, we have established partnership with a commercial poultry vaccine producer ""MSD Animal Health"". Through this collaboration, we will investigate how our developed targeted antigen delivery vaccine (TADV) formulation can further be optimised to i) induce even more rapid immunity and provide more potent and broader immune responses against antigenic AIV variants infecting poultry in different geographic regions; ii) enhance the production and delivery methods in chickens using our well-established insect cell cultures and recombinant viral vector (herpesvirus of turkey) system. The result obtained from this proposed research would provide a novel next generation improved AIV vaccine and a platform for improvement of vaccine technology against other important livestock and human pathogens. Availability of these novel highly protective and cost-effective disease control tools and strategies should minimise the impact of infectious diseases on farm animals, and offer substantial indirect economic, public health, environmental and social benefits to the UK and rest of the world.",,2024,N/A,667893.79,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Pre-clinical studies | Vaccine design and administration,2021 +P30355,2888084,Discovering patterns in the genome of RNA viruses that drive evolution and regulate replication,"All genomes are composed of four bases, A, C, G and T (or U, in RNA genomes and mRNAs). If these were encoded randomly, every genome would comprise ~25% of each base; but this is not the case. Similarly, there are 16 possible combinations of nucleotide pairs, or dinucleotides. With random representation, each dinucleotide would occur 1/16 or 6.25% of the time, but in the genomes of all organisms, from bacteria to humans, TpA dinucleotides ('p' represents the phosphate bridge in the DNA backbone) are under-represented. The reason(s) are unknown, but intriguingly, RNA viruses mimic their hosts by suppressing UpA in their genomes [1]. When a virus infects a cell, this triggers an antiviral response resulting in hundreds of genes being upregulated. One such gene encodes the Ribonuclease L (RNaseL) enzyme. In 1981 it was reported that mRNA is cleaved at UpA motifs by RNaseL [2], potentially explaining why UpAs are suppressed in the genomes of viruses and their hosts. However, when UpAs are added into virus genomes, virus growth is impaired, but depletion of RNaseL does not remove the impairment (unpublished data from our lab), suggesting that other factors may be involved. RNAseL is a known to have antiviral activity, and its activation drastically alters cellular gene translation, leading to the synthesis of novel proteins [3]. We hypothesise that RNaseL activation may also change the profile of viral proteins produced during infection. In this project you will characterise how UpA dinucleotides influence virus replication, and determine whether RNAseL alters viral protein production during virus infection. Specifically you will: 1. Design and synthesise mutants of influenza A virus with increased UpA content, and characterise the impact of UpA introduction on virus replication. You will test whether RNaseL depletion restores virus fitness. 2. If RNaseL restricts virus replication, you will characterise the mechanism. If RNaseL is not restrictive, you will use a small screen based approach to identify cellular factor(s) that are important for cellular UpA recognition. 3. Generate knockout RNAseL cells and infect them with influenza A virus, then perform mass spectrometry to determine whether RNAseL impacts the profile of viral peptides produced during infection. You will learn laboratory skills including how to perform virus infections, molecular biology techniques including CRISPR, mass spectrometry, and in silico methods for virus genome recoding. [1] Gaunt and Digard, 2022. Compositional biases in RNA viruses: Causes, consequences and applications. WIREs RNA, e1679. [2] Wreschner et al., 1981. Interferon action - sequence specificity of the ppp(A2'p)nA-dependent ribonuclease. Nature, 289: 414-7. [3] Karasik et al., 2021. Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences. Nucleic Acids Research, 49 (11): 6007-26.",,2027,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30358,BB/V017365/1,Genetically ENgineered BIOsensors to detect BIological Threats (GENBIOBIT): Influenza A Virus,"We want to pioneer a new class of genetically engineered biosensors that can rapidly, sensitively and efficiently detect and diagnose infectious diseases to address the fast-changing landscape of human and animal population biosurveillance. Infectious diseases and emerging biological threats (natural, accidental or deliberate) are a challenge to UK security. We aim to deliver a step-change in current technological capability to overcome the current barriers that prevent cell-based biosensors to work in the field without sample preparation at ambient temperature for a prolonged period of time. This new technology could be part of a nationwide biosurveillance network of multiple biological threats with large economic and societal impact. In particular, we want to establish proof-of-feasibility for the influenza A virus. IAVs have proven potential to damage livestock welfare and productivity, as well as to cause human pandemics. They thrive in wild animal populations and can transmit to farmed animals. As well as causing direct economic harm, this then provides a gateway for zoonotic infections (e.g. avian H5N1 and swine H1N1 subtypes). The worst recorded instance is the 1918 pandemic that resulted in the deaths of more than 50 million people. To reduce economic impacts as well as public health risk, there is a need to monitor and control the disease in the animal source. Despite multiple IAVs biosensors have been developed in the lab, there is currently no practical applications. We wish to introduce a key innovation that will enable their use in the field, and in particular in animal drinkers. The key innovation is a synthetic membrane receptor that 1) has an extracellular domain that is highly selective to IAVs 2) has an intra-cellular domain that activates specific genes of interest controlling cell behavior upon virus binding 3) can be expressed in a resilient cell line originating from rainbow trout gills, that was demonstrated to survive over a range of temperature from more than a year in the field without maintenance to test water toxicity. Finally, by combining multielectrode arrays and multiple engineered cell lines (with the same selectivity to the virus but encoding different cell behavior) we will have a multiplexed electronic readout improving considerably the robustness and its potential to discriminate (diagnose) IAVs from others biological threats (toxins, bacteria, viruses) with faster response time and sensitivity than signals associated with pathogen associated cell death. Phone-sized hybrid sensors (containing several gene-engineered cells interrogated in parallel by multi-electrode arrays) will be demonstrated in the lab (TRL3) to detect and discriminate between IAVs and other pathogens or toxins. Our approach harnesses synthetic biology and data science to monitor existing infectious diseases and thus rapidly adapt to emerging biological threats. The extra-cellular part of the synthetic receptor can be quickly re-engineered to address other biological threats. Genetically engineered Biosensors will pave the way towards networks of biosensors that can be deployed in the field sampling water (drinkers, ponds, lakes) or volatiles (e.g. in air conditioning system) and could directly alert or feed real-time data to monitoring centres. This novel technology, demonstrated with a portable biosensor detecting IAV, will also provide a broader impact on the life science community for which novel tools for the detection of target binding are highly desirable (e.g. drug screening, infectious diseases). This will also provide a new tool for the emerging field of bio-computation. This is a highly interdisciplinary project with great potential for the PDRAs involved to work across the discipline of virology, synthetic biology and biosensing.",,2022,N/A,184979.53,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P30359,2734734,Developing machine learning tools to investigate evolutionary trajectories in emerging viral infectious diseases,"TBC Understanding the evolutionary trajectory of an emerging viral pathogen is crucial to both surveillance and the development of therapeutic interventions. This project aims to advance our understanding of the mutational pathways followed as a virus adapts to its host. The unprecedented and large quantity of genomic and molecular data linked to phenotypic health data that has been generated in response to the current Sars-CoV-2 pandemic, as well as existing data from influenza and other viruses, allows us to address this question at the molecular level. Using a combination of computational techniques, including structural bioinformatics and machine learning / deep learning, the effects of successive combinations of mutations in proteins involved in viral/host interactions will be evaluated and predicted. To test and appraise the computation tools a range of lab based molecular virology techniques will be employed. Including in vitro virus culture, cloning, site-directed mutagenesis, reverse genetics, recombinant protein expression and purification, pseudovirus construction, classical and pseudoneutralisation assays. The computational tools and insights from this project can be applied to future emerging viral pathogens. The range of highly sought after skills developed within the project will give a firm bases for a future career in academia and/or industry.",,2026,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P30360,MC_UU_00034/3,Virus cross-species transmission. Defining the immunological barriers to viral emergence,"Humans are constantly exposed to a variety of animal viruses. Understanding why most of these viruses fail to spillover and thrive in human populations is crucial to devise optimal strategies to manage viral emergence. Our programme aims to understand diverse immunological barriers to virus cross-species transmission. Our hypothesis is that the genetic and immunological variability of each individual or species helps define susceptibility or resistance to virus cross-species transmission. Our first aim is to identify those genes that are activated immediately after virus infection (known as interferon-stimulated genes, ISGs) and block respiratory viruses. Our second aim is to create a risk assessment framework to identify those specific viral proteins (and specific amino acid residues within the proteins) that favour the spillover of avian influenza viruses into the human population. The third and last aim of the programme is to understand the antibody landscape in humans and selected animal species, in order to estimate the impact of cross-neutralising antibodies and, at the population level, cross-immunity on constraining viral emergence. At the end of this programme, we will be able to translate our discoveries by delivering actionable data that can support the risk assessment of the zoonotic potential of viruses.",,2028,N/A,3732651.09,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,,Coronavirus | Paramyxovirdiae | Orthomyxoviridae | Novel Pathogen | Other,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2023 +P30361,2434526,Developing iPSC models of the airway epithelium to understand host - virus interactions,"The airway epithelium acts as the critical interface between the environment and organ physiology. It acts as a barrier to potential pathogens and extraneous particles and helps regulate host defence mechanisms, including the inflammation process. Under normal conditions, the bronchial epithelium is composed of ciliated columnar, mucus-secreting goblet and Clara cells that secrete surfactant. Respiratory viruses including respiratory syncytial virus (RSV), influenza virus and rhinovirus (RV) are common and cause significant illness in children and also exacerbate existing lung diseases. A greater understanding of the molecular basis of the virus-airway epithelial interactions in donors of different genetic backgrounds or in different environmental context will provide mechanistic understanding. Accumulating evidence suggest that genetic variants mediate the extent and nature of the virus interaction, e.g. CDHR3 variants and RV-C (PMID: 24241537, PMID: 30930175). The most common approach to study bronchial epithelial cell - virus interactions in human context is to isolate airway epithelial cells using bronchoscopic brush technique and then culture the cells using air-liquid interface (ALI) differentiation (PMID: 22287976). ALI cells form an epithelial barrier that closely resembles the in vivo architecture and is composed of basal, goblet, and ciliated cells. However, the bronchoscopic procedure is invasive with life threatening risk to the individual, adequate numbers of cells are hardly collected and cells have a limited lifespan. These factors make the development of a non-invasive, sustainable model of the human airway epithelium that incorporates the genetic complexity of human donors for mechanistic studies highly desirable. The differentiation of induced pluripotent stem cells (iPSCs) to mature cell types shows great promise to provide personalized disease modelling including mechanistic studies. Development of iPSC models that encapsulate mature multiciliated cells in a functional airway epithelium with clara, goblet, and basal cells indicative of a polarized epithelial-cell layer have recently been developed (PMID: 24706852). However, more work is needed to advance this area providing a robust representative model the captures the complexity of the airway epithelium and can be used to investigate the host epithelial - virus interactions representative of that occurs in the human lung. The hypotheses underlying this proposal are i) iPSC models can capture the complexity of airway epithelium, ii) these models will allow the study of RSV, influenza and RV induced responses providing unprecedented insight into the molecular basis of specific and overlapping virus driven effects and iii) by studying viral induced changes in cells derived from donors that carry specific genetic variants and/or introduce changes using CRISPR/Cas9 we will identify potentially new/novel understanding of pathways that could be the target of new anti-viral drug development. Key stages to the project: 1. Develop and optimise culture conditions for the generation of airway epithelium in vitro complete with clara, goblet, and basal cells using iPSC and ALI differentiation. 2. Compare and contrast at the functional (barrier), morphological, protein and transcriptomic (RNA-seq) level these iPSC derived airway epithelial layers with the current gold standard derived from donor bronchial epithelial cells isolated by bronchoscopy and grown at ALI. 3. Investigate virus - epithelial cell interactions in both the iPSC and HBEC models using cells from controls and patients with respiratory conditions e.g. asthma to understand the effects of genetic variation (in genotype donors and/or introduced by CRISPR/Cas9) on these responses. This project represents an exciting PhD opportunity and brings together significant expertise across schools and disciplines including the use of physiological relevant airway models, genetics (Sayers)",,2024,N/A,,Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Other,Unspecified,,,,,,,,Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis,2020 +P30364,BB/Y007069/1,Flu:Trailmap Transmission and risk of avian influenza: learning more to advance preparedness,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2025,N/A,298213.74,Human Populations | Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,H5N1 | Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Pathogen: natural history, transmission and diagnostics","IPC at the human-animal interface | Restriction measures to prevent secondary transmission in communities | Disease surveillance & mapping | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30365,BB/X00614X/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,147506.93,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30366,BB/X006166/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,410229.34,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30367,BB/X006123/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,221776.41,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30368,BB/Y007271/1,FLU:Trailmap: Transmission and risk of avian influenza: learning more to advance preparedness,"High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health globally and threatens human health. Incursions of HPAIV into the UK have increased significantly since 2020 with over 350 infected premises being detected between 2020 and 2023. Wild bird populations have also suffered significant mortalities across multiple species, with a shift to infection of seabirds enabling over-summering of virus infection in UK birds for the first time. Whilst virus incursions have been restricted to the H5N1 subtype, the ability of these viruses to exchange genetic material means that over 12 different H5N1 viruses have been detected in the UK. Further, the increased infection pressure has meant that the virus has spilt over into scavenging mammalian species with 23 detections of HPAIV in wild mammals since 2020. This project is in response to this extreme increase in detection of HPAIV infection in the UK and is divided across five work packages (WPs) to improve our understanding of HPAIVs, help mitigate incursions and refine approaches to future prevention strategies. Work-package (WP1) will improve our understanding of on-farm biosecurity practices, to define weaknesses in existing barriers and determine how to implement effective counter measures. Through detailed investigation and by conducting multi-sectorial interviews, the adherence and effectiveness of existing biosecurity interventions will be assessed. Outputs will provide insight into effectiveness and challenges to implementation which will be used to improve biosecurity in the field. WP2 will improve our understanding of factors which contribute to the circulation of these viruses, including understanding the complex interactions amongst wild bird networks and with poultry. Viral genetic and epidemiological data from the field, and data generated through the other WPs, will be input into models that will provide insight into 'high-risk' activities. Modelling populations and their interactions will link WP1 and WP5 to help understand the effectiveness and impact of existing and future control and mitigation actions. WP3 will improve our understanding of HPAIV transmission dynamics in both wild birds and poultry. By undertaking biological sampling across wild bird populations, we will develop risk-based surveillance programmes and model interactions at wild bird and poultry interfaces. This will enable a definition of high-risk incursion sites and critical wild bird populations responsible for potential sustained transmission within the environment. Outputs will feed into WP2 and enable a greater understanding of the potential reservoirs of infection as well as factors that drive incursion of disease from bird reservoirs into the poultry sector. WP4 will assess virological factors that drive differential disease outcomes. Both viral infectivity and factors that dictate infection of different species will be assessed. This will enhance our understanding of virological interactions and define the role of viral factors that contribute to viral emergence. This WP will also link to outputs from other WPs to examine the mechanisms that drive viral diversity and factors that may enable adaptation to different hosts. Finally, WP5 will assess the role of host factors, including immunity, in governing susceptibility, outcome, epidemiology, and virus evolution. This WP will investigate how molecular differences between species contribute to disease outcomes and define how antibody responses to different virus proteins impact upon the potential of virus emergence including variations across different hosts. Viral domains that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. We will also assess how the implementation of vaccination might impact on outbreaks and hence will inform future mitigation strategies.",,2025,N/A,986070.16,Animals | Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Other,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,H5N1,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures | Disease surveillance & mapping | IPC at the human-animal interface",2023 +P30369,BB/X006174/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health, with a risk of human infection that demands continuous monitoring and control globally. Incursions of HPAIV into the UK and Europe have increased significantly in the last two winter seasons. During the 2020/21 season, 26 infected poultry premises (IPs) were detected across the GB (24 IPs) and NI (2 IPs) with over 300 wild birds testing positive, a record outbreak season at that time. The 2020/21 outbreak was dominated by the detection of the HPAIV H5N8 subtype, although an undercurrent of alternative H5 based subtypes was detected including H5N5 in poultry, and H5N1 and H5N3 also being detected in wild birds. This season was then followed by a significant escalation in cases due to new incursions during 2021/22, with over 100 IPs across the UK, all caused by H5N1 HPAIV. During 2021/22, more than 800 wild birds have tested positive for H5N1 virus, with just a single wild bird detection of H5N8. This project targets this extreme emergence of HPAIV in the UK (and beyond), to improve our understanding of HPAIVs to help mitigate incursions and refine approaches to future prevention strategies. Work-package (WP1) aims to improve the understanding of HPAIV transmission dynamics for these viruses in both wild birds and domesticated poultry. By undertaking biological sampling and data analysis we will design more effective, risk-based surveillance programmes and model interactions at wild bird and poultry interfaces, defining geographical sites and wild bird populations of high risk, and linkages to farm incursions. Outputs will enable a greater understanding of the reservoir of infection, wild waterfowl, as well as factors that drive incursion of disease from this reservoir into the poultry sector. WP2 aims to assess antigenic diversity across the HPAIVs detected in the UK in recent years in context of co-circulating low pathogenicity AIVs, in the absence of disease, both in wild waterfowl and poultry. The sequential emergence of HPAIVs suggests that prior immunity from 2020/21 to H5N8 virus was insufficient to prevent emergence and dominance of H5N1 during 2021/22. This WP will define how antibody responses to different virus surface proteins impact upon the potential of virus emergence. This feature of infection will utilise post-infection antisera derived from natural and experimental infection to study immune escape. Areas of the virus that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. This will enable focused studies that will help develop our understanding of what factors might influence future mitigation strategies. Finally, factors that drive differential disease outcomes, outside of the viral surface proteins, will be assessed in WP3. Here, novel systems will be developed to assess viral infectivity and host range which in turn will enhance our understanding of virus-host interactions and define the role of internal viral proteins, critical to viral replication, driving virus diversity and emergence with consequent disease outcomes. WP3 will utilise outputs from WP1 and WP2 to examine the mechanisms that drive the emergence of virus variants, enabling differential adaptation to different hosts. Experimental systems that enable individual components of the viral replicative machinery to be assessed and compared will be developed, utilising our ability to generate viruses in the laboratory to defined genetic specification. Minimal infectious doses and related growth kinetics will be assessed to refine work in animal models. Utilising expertise from across the UK in different experimental systems, with access to a range of laboratory facilities, the partners will link across WPs to generate impactful outputs to enhance our understanding of these emerging pathogens.",,2023,N/A,527802.34,Animals | Viruses | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,H5N1 | Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission | Disease transmission dynamics",2022 +P30370,BB/X006158/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,251312.08,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30371,BB/X006107/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,44911.85,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30372,BB/X006182/1,Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2023,N/A,157297.08,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors","Pathogen genomics, mutations and adaptations | Immunity | Animal source and routes of transmission",2022 +P30373,2886154,Coronaviruses of UK carnivores,"Coronaviruses of wild animals display frequent species jumps into new species, most recently causing the COVID-19 pandemic. Our recent work monitoring UK carnivores and mustelids (weasels, stoats, badgers, foxes, otters) for spillover of SARS-2 will be continued and extended in this project. While so far SARS-2 has not been found in UK wildlife we have sequenced novel viruses in stoats but don't know much about these viruses apart from their genetic sequence. This group of viruses is prone to forming recombinant viruses in domestic animals (cats and dogs) with some of these crossing the species barrier sporadically into people (potential spill over into production animals is unknown). It likely that dog and cat viruses also infect many of these species but this has been little studied. This project will focus on screening existing sample banks (and extending sample collection with existing collaborators) for related alphacoronaviruses in UK carnivores and mustelids. The project will characterise the epidemiology of the viruses in their host species and interactions with other pathogens of concern such as bovine tuberculosis in badgers or avian influenza in otters and foxes. The project will also examinethe recombination and cross species transmission potential of these viruses. Further work may include cell culture experiments to characterise how recombination of canine and feline alphacoronaviruses occurs and expression of proteins from alphacoronaviruses to assess cross reactivity with SARS-2 in serology assays (which may complicate screening of wildlife for SARS-2)",,2027,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2023 +P30375,2438520,Transient models to assess transmission and control of airborne infection risks in a respiratory ward,"Airborne transmission is an infection route for many diseases including influenza, COVID-19 and opportunist pathogens in hospitals. Quantifying risks are necessary to determine appropriate control strategies, both in terms of engineering approaches such as ventilation, and management strategies such as treating, locating and scheduling hospital patients. However airborne transmission is complex to evaluate as it requires understanding of the airflows, infection dynamics and human-environment interactions. The COVID-19 pandemic has shown that we have significant lack of knowledge in this area, particularly around the role of airflows in managing different sizes of airborne particles and the effectiveness of different solutions. Previous studies have developed models to link airflow and infection dynamics to assess the hospital environment, including looking at the influence of airflow patterns in multi-room environments and stochastic effects in small populations. However current models generally assume that both the infection parameters and airflows are steady-state as the outbreak evolves in time. This project aims to explore the influence of transient effects in both time and space to evaluate how short term events can influence individual risk and the overall dynamics of an outbreak. To this aim, we will combine transient airflow models from CFD simulations with stochastic infection dynamics models. The models will be applied to the respiratory wards at St James's Hospital in Leeds, with the objective of evaluating the effectiveness of interventions, including application of air cleaning devices.",,2024,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,Unspecified,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Infection prevention and control,IPC in health care settings,2020 +P30377,BB/Y007298/1,FLU-Trailmap: Transmission and risk of avian influenza: learning more to advance preparedness,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2025,N/A,566505.07,Human Populations | Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,H5N1 | Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Pathogen: natural history, transmission and diagnostics","IPC at the human-animal interface | Restriction measures to prevent secondary transmission in communities | Disease surveillance & mapping | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30378,BB/Y007042/1,Flu: TrailMAP Transmission and risk of avian influenza: learning more to advance preparedness,"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2025,N/A,242393.59,Human Populations | Other,Unspecified | Not applicable,Adults (18 and older) | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Other | Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Pathogen: natural history, transmission and diagnostics","IPC at the human-animal interface | Restriction measures to prevent secondary transmission in communities | Disease surveillance & mapping | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30379,BB/Y007352/1,Flu Trailmap (Transmission and risk of avian influenza: learning more to advance preparedness),"Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2025,N/A,844855.65,Human Populations | Unspecified,Unspecified,Adults (18 and older),Unspecified,Unspecified,Other,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Pathogen: natural history, transmission and diagnostics","IPC at the human-animal interface | Restriction measures to prevent secondary transmission in communities | Disease surveillance & mapping | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30380,MR/W024977/1,Dynamics of human T cell memory in blood and secondary lymphoid tissue in shaping vaccine induced immunity in ageing,"Vaccines protect by training the immune system to retain memory of an infection. This is made up of different kinds of cells which can retain information, like bits in a computer software system. This is called immune memory. It is this feature which allows us to be protected after vaccination if we encounter an infection. We do not fully understand the processes involved. One very important type of T cell interacts with B cells to help them make antibodies. These interactions happen in specialised tissues called lymph nodes. These are small kidney-shaped organs found together in clusters in certain areas such as the underarm. It is here that T cells and B cells meet the vaccine or parts of the vaccine and as a result, the cells respond, change and multiply. In older people, we know that the processes of immune priming, maintaining immune memory and recalling it may all happen differently, perhaps more slowly, but we don't know precisely why. One possibility is that T cells respond differently in older people. Vaccines for older people often need a high dose or an extra activating component. Although lymph nodes are important, they have not been well studied in humans. This is because taking a lymph node sample requires different skills from taking blood and these have not previously been invested in. A clinician who is skilled in ultrasound-guided needle biopsy, is needed. This means that we are missing key information in understanding how vaccines work, and how we might design them better in different circumstances; for older people for example, or to tackle highly complex infections that rapidly change such as HIV, flu and SARS-CoV-2. This Fellowship aims to change that. Not just for the duration of this project but for the future of vaccine science. Firstly, I will develop bedside imaging to determine which lymph nodes are responding to the vaccine and which are not. At present this is sometimes possible with greyscale ultrasound but the results are not always reliable, or with PET/CT but this involves a dose of radiation. I believe we can do this more frequently and in more people using harmless ultrasound. Volunteers will be vaccinated with a vaccine against influenza and attend for an imaging appointment on multiple days before and after vaccination. Each time they attend they will have a scan to see the size and blood flow in the lymph nodes near to the site of vaccination. This will determine the best site and best day on which to take a sample using these types of vaccines. Secondly, I will use the ultrasound to guide a fine needle aspiration (USFNA) biopsy to take a sample of the lymph node before and after vaccination with influenza vaccine. I will also ask volunteers to give a sample of the blood at the same time. Samples from lymph nodes on the same side and opposite (control) side can be taken. The cells will be stained and measured using a machine called a flow cytometer so that I can determine which are T cells, what type of T cells, what they are responding to and whether they are growing in number (in cell cycle). I will compare this in the blood and in the lymph node. Thirdly, I will measure how individual T cells are responding to vaccination by testing the ribonucleic acid (RNA) that they are producing. This will indicate in detail how different types of T cells respond to the vaccine. To understand how age might affect the immune response, I will ask people of different ages to participate. My vision is to generate a picture of how T cells respond to vaccines in lymph nodes, and to demonstrate how, and why, this changes with age. This will provide new insight for the future of vaccine design.",,2027,N/A,1814575.96,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Characterisation of vaccine-induced immunity,2022 +P30382,EP/V008404/1,VIRTACs - Protein Degradation as an Anti-Viral Strategy,"As highlighted by the current Covid-19 pandemic, viruses are a constant threat to human health and prosperity. Viral infections kill millions of people every year and population growth, international travel and climate change mean that human populations are increasingly vulnerable to emerging viral threats. Further to the severe morbidity and mortality caused by viruses, lost productivity and livestock deaths mean viruses place a considerable burden on the global economy (estimated in the tens of billions of pounds worldwide each year). Developing new strategies to combat viral threats is of tremendous importance, as recognized by many organizations including the United Nations, World Health Organization, and UK Government. Most antiviral drugs work through a classical mechanism that involves a 1:1 interaction of the drug with its target. An emerging strategy in Medicinal Chemistry seeks to overcome this ""occupancy based"" limitation using a new mechanism called protein degradation. There are lots of potential advantages to the protein degradation approach, but its new enough that it hasn't really been explored much in an antiviral context. This project will explore the protein degradation mechanism in targeting 3 viruses of importance to human health: HIV, influenza, and the SARS-CoV-2 virus that is causing the current Covid-19 pandemic. Although we're not aiming to generate a new drug during this project period (that takes longer and costs more), we believe that this project will lay the groundwork for important new therapies in the future. There's no doubt that these therapies will be needed, as viruses are constantly developing resistance.",,2024,N/A,568439.62,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Therapeutics research, development and implementation",Pre-clinical studies,2021 +P30383,NE/X013502/1,Population-level impact and geographic spread of highly pathogenic avian influenza virus H5N1 outbreak in gannets,"For some unfortunate observers, the summer of 2022 will be remembered for an outbreak of highly pathogenic avian influenza (HPAI), which led to the death and suffering of many thousands of seabirds at colonies across the North Atlantic. These internationally important populations were already under intense pressure from anthropogenic change; therefore, we need to know urgently not only the impact of this outbreak but how it might be spreading. We propose using detailed individual-based data to estimate the impact of HPAI on a species particularly severely impacted in the recent outbreak, the northern gannet. Using capture-mark-recapture techniques we will estimate adult survival probability, a much more robust measure than conventional population censuses or counts of dead birds, at two large UK colonies - one which has been severely impacted by HPAI (Bass rock in Scotland), while the other remains virus free (Grassholm in Wales). We will also track inter-colony movements using bird-borne GPS devices which transmit via the mobile phone network. This will provide vital information on which components of the population are most likely to spread the virus (by comparing the usually colony-faithful breeders with the more itinerant immature birds) and inform our metapopulation model for gannets in the northeast Atlantic. This model will enable us to predict the impact of HPAI across virtually the entire gannet breeding range, under the realistic scenario of inter-connected colonies. Finally, we will be able to identify populations particularly vulnerable to the combined effects of viral outbreaks and other anthropogenic stressors such as the construction of offshore wind farms.",,2023,N/A,103733.77,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,H5,,,,H5N1,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Animal and environmental research and research on diseases vectors,Animal source and routes of transmission,2022 +P30385,BB/V017586/1,Fluorous-based diagnostic platform for multiplexed diagnosis and differentiation of viral infections,"Viral infections pose one of the biggest global threats to human populations and agriculture. Successful prevention, monitoring and treatment of viral infections requires the availability of fast and reliable diagnostic methods which can not only sensitively, but rapidly detect a viral infection of interest and differentiate between viral infections. This is particularly important in the winter months where rapid diagnosis of viral infections emerging from SARS-Cov-2 relative to influenza strains is essential in order to assist medical practitioners to suggest the most appropriate interventions and treatment. At present, methods do not exist which can rapidly detect viral infections in a low-cost, point-of-care device. We propose to develop a biosensing technology which can not only detect viral components, but also has the potential for the platform to be reusable and regeneratable. Central to these developments is the use of fluorous technology as a tool to immobilise elements which detect viral components. Much akin to Teflon, fluorous technology has the dual advantage as a method which can immobilise molecular components which have a complementary fluorous tag, and reduces non-specific binding to non-fluorous biomolecules, thus improving the sensitivity of the approach. Furthermore, the fluorous-directed immobilisation event is inherently reversible by a simple washing step with organic solvent. In this proposal, we will demonstrate the modularity of the strategy to detect viral RNA (by RT-PCR) or protein (by direct detection of intact viral particles). This will provide a powerful new tool for the biosciences which has the potential to be used for any application which requires rapid detection of pathogenic infections.",,2022,N/A,207911.91,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2021 +P30386,10108315,Ecology and biology of HPAIV H5 (Kappa-Flu).,"The global emergence of highly pathogenic avian influenza (HPAI) viruses and the subsequent adaptation to wild birds has resulted in record mortality of wild birds and poultry and is developing into an enzootic threat for wildlife, poultry and human health in Europe. The ongoing evolution of HPAI virusesis expanding their geographical distribution and host range. To deal with this global problem, KAPPAFLU brings together top experts from Europe, North America and Asia. The overall objective of KAPPA-FLU is the characterization of key viral, host-related and environmental factors that determine the maintenance and the long-distance spread of HPAI viruses in wild birds, with the goal of improving capacities for risk-based surveillance, prevention and control of HPAI in poultry and wildlife, and its potential impact on human health. KAPPA-FLU will follow three research themes. Theme A (Disease ecology) provides a deep understanding of the population dynamics of HPAI virusesin migratory waterbirds and spill-over hosts, both resident wildlife and poultry, through risk-based surveillance strategies, and accounting for the impact of climate change. Theme B (Virology) studies the evolution of HPAI viruses in wild birds and poultry and the resulting increasing risk to humans and other mammals. Based on the above results, theme C (Agro-ecosystem risk) identifies and models prevention and control strategies (including vaccination) using machine learning algorithms. Actors from different sectors of society will, through the Multi-Actor Panel, play key roles in translating results into policy and practice. In this way, KAPPA-FLU will make stepwise advances in knowledge of the population dynamics and evolution of HPAI, and thus contribute to a sustainable poultry production system and improved public health.",,2027,N/A,1095620.58,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies | Infection prevention and control","Pathogen genomics, mutations and adaptations | Animal source and routes of transmission | Disease transmission dynamics | Impact/ effectiveness of control measures | IPC at the human-animal interface",2023 +P30387,10085195,Kappa-Flu,"The global emergence of highly pathogenic avian influenza (HPAI) viruses and the subsequent adaptation to wild birds has resulted in record mortality of wild birds and poultry and is developing into an enzootic threat for wildlife, poultry and human health in Europe. The ongoing evolution of HPAI virusesis expanding their geographical distribution and host range. To deal with this global problem, KAPPA FLU brings together top experts from Europe, North America and Asia. The overall objective of KAPPA-FLU is the characterization of key viral, host-related and environmental factors that determine the maintenance and the long-distance spread of HPAI viruses in wild birds, with the goal of improving capacities for risk-based surveillance, prevention and control of HPAI in poultry and wildlife, and its potential impact on human health. KAPPA-FLU will follow three research themes. Theme A (Disease ecology) provides a deep understanding of the population dynamics of HPAI virusesin migratory waterbirds and spill-over hosts, both resident wildlife and poultry, through risk-based surveillance strategies, and accounting for the impact of climate change. Theme B (Virology) studies the evolution of HPAI viruses in wild birds and poultry and the resulting increasing risk to humans and other mammals. Based on the above results, theme C (Agro-ecosystem risk) identifies and models prevention and control strategies (including vaccination) using machine learning algorithms. Actors from different sectors of society will, through the Multi-Actor Panel, play key roles in translating results into policy and practice. In this way, KAPPA-FLU will make stepwise advances in knowledge of the population dynamics and evolution of HPAI, and thus contribute to a sustainable poultry production system and improved public health.",,2027,N/A,788868.08,Animals | Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other | Unspecified,,,,,,,,Pandemic-prone influenza,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,Animal and environmental research and research on diseases vectors | Epidemiological studies,Animal source and routes of transmission | Disease surveillance & mapping,2023 +P30388,BB/Y00700X/1,"Flu:Trailmap ""Transmission and risk of avian influenza: learning more to advance preparedness""","Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.",,2025,N/A,341461.35,Human Populations | Other,Unspecified | Not applicable,Adults (18 and older) | Not Applicable,Unspecified | Not applicable,Unspecified | Not applicable,Other | Not applicable,Non-Clinical,,Orthomyxoviridae,H5 | Other,,,,Other,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Infection prevention and control | Epidemiological studies | Pathogen: natural history, transmission and diagnostics","IPC at the human-animal interface | Restriction measures to prevent secondary transmission in communities | Disease surveillance & mapping | Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2023 +P30390,76242,"Sugars, Enzymes And Diagnostics (SEAD)","In any infectious disease outbreak, the rapid triage of potential carriers of infection is essential to control the spread of infection and to allocate resources efficiently. Iceni Diagnostics is repurposing the technology most famously used in the home pregnancy test kit to create a new generation of rapid, point-of-care diagnostics. These studies are being carried out in close collaboration with clinical laboratories from the NHS, to ensure rapid feedback on ease of use, sensitivity and specificity with real-life samples. The scientific basis of these new tests relies on the exploitation of the carbohydrates that viruses and bacteria attach to on human cells, which we will immobilise in our devices. The key advantage of this technology is that is easy to produce and can be scaled up, using established manufacture and distribution chains, to meet the substantial demands for immediate and recurrent infectious diseases testing. Specific products under development include devices to detect equine influenza in stables, norovirus in hospital wards, and Covid-19, the latter to support the NHS, homes and individuals wanting to self-test before returning to work, associating with neighbours and family etc. An immediate goal for Iceni Diagnostics is to devise rapid, flexible and scalable ways to make the bespoke carbohydrates required for diagnostics applications. To this end, partnership with Manchester Institute of Biotechnology (MIB) provides access to state-of-the-art knowledge in green ways to make sugars. The secondment to Iceni Diagnostics of an MIB researcher provides an ideal way to build the academic-industry relationships and to provide an individual with a strong University background with experience of how their skills and expertise may be deployed in a biotech/medtech SME setting.",,2022,N/A,146886.07,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Other,,,,,,,,COVID-19 | Pandemic-prone influenza | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors",Diagnostics | Animal source and routes of transmission,2021 +P30391,EP/Y009878/1,Identifying pathogen exposure via immunological memory in ancient populations using proteins and DNA,"The vision: detecting all the infections an ancient individual was exposed to in their life, not just what might have killed them! Infectious disease has likely had the greatest impact on human evolution, yet it has not been possible to assess the true burden of communicable disease on historic human populations. Next Generation Sequencing has made it possible to identify certain ancient pathogens in victims and the applications of paleoproteomics are rapidly developing; however, we have been unable to distinguish between survivors of communicable disease and those who were never exposed, nor routinely detect the most common circulating illnesses and causes of child mortality (many of which are viruses, chemically unstable at the DNA level). To understand how shifts in environment and/or cultural practices have shaped our susceptibility through time, it is necessary to be able to directly study both pathogens and our immune response to them. AncientAntibodies will provide this ability by exploiting emerging paleoproteomics methods, ancient DNA, immunological memory and well-preserved, well-studied human skeletal remains from epidemic contexts- allowing unprecedented insight into the history of infectious disease. It will develop protocols for (1) isolating, sequencing and matching ancient antibodies to pathogens and (2) identifying important, ancient viruses (e.g. measles, mumps, influenza) in skeletal remains. Both are made possible by recent advances in paleoproteomics and metagenomics. These novel protocols will build the foundation for a new field of study: Ancient Immunomics and provide the methodological framework for settling long-standing debates regarding the impact of environmental, cultural and genetic shifts on the evolution of the human immune system. It will allow researchers to directly assess past individual and community immune status. The groundwork laid by AncientAntibodies will be an indispensable, transferable resource for future studies of the human past.",,2028,N/A,1616225.96,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,European Commission | UK Research and Innovation (UKRI),United Kingdom | Europe,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity",2023 +P30392,10061632,"Quality, yield and cost optimisations of in vitro transcription reactions for saRNA therapeutics","The potential of nucleic acids as vaccines and therapeutics is only just being realised and the success of the Covid mRNA vaccines is due in part to the rate at which scale-up and manufacture was possible. VaxEquity is a biotechnology company seeking to develop novel, second-generation RNA based vaccines and therapeutics. Working in collaboration with the Centre for Process Innovation, this project will drive efficiencies in the manufacturing process for second generation RNA vaccines and therapeutics based on self-amplifying RNA and, specifically, for amulti-valent saRNA flu vaccine. The project will identify and define experimentally the Critical Quality Attributes (CQAs) i.e. the key properties for saRNA and the manufacturing variables that impact these CQAs for the process of RNA transcription (the creation of active RNA molecules from the more stable DNA template) in batch and fed batch processes. The process of capping the RNA to enhance stability, processing and translation will be evaluated in tandem with the manufacturing process and as a separate reaction after the primary saRNA synthesis is complete. Studies will be run at small, laboratory scale to identify the optimised conditions and the factors that critically impinge on these conditions. Optimised conditions will be tested to establish scalability for the subsequent manufacturing of a broad-acting saRNA influenza vaccine to proceed into preclinical and clinical development. Manufacturing nucleic acid-based medicines is expensive and through the optimisation of conditions for saRNA, which has the potential to reduce dose compared to mRNA by \>10-fold, significant savings from both raw materials and the size of future dose requirements can be achieved. The benefits of the project for the UK will be to identify, establish and protect an optimised process for saRNA manufacture in a partnership between the UK's leading independent technology innovation centre that has the right experts and practical capabilities for effective innovation of complex nucleic acid therapies and UK-based RNA vaccine and therapeutics biotechnology company VaxEquity.",,2024,N/A,750245.22,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P30393,MR/R021562/2,PROTEOME-WIDE IDENTIFICATION OF RNA-BINDING PROTEINS PLAYING CRITICAL ROLES IN VIRUS INFECTION,"Many viruses that infect humans have a genome made of RNA instead of DNA, including human immunodeficiency virus, hepatitis C virus and influenza virus. The viral enzymes involved in RNA replication display a high mutation rate, allowing rapid evolution of the virus, which helps it to evade immune defences and allows the emergence of resistance to antiviral drugs. RNA genomes are small, often encoding just a dozen proteins. By contrast, the human host cell dedicates ~1,500 RNA-binding proteins (RBPs) to RNA metabolism. Since viral genomes can only encode a handful of these proteins they rely on host proteins to complete their biological cycle. Host RBPs can also play another important role in infection, by acting as ""sensors"" that detect unusual molecular signatures present in viral RNAs and their replication intermediaries. Upon binding, these ""sensors"" trigger the antiviral response to alert neighbouring cells and provide an opportunity to block virus infection. Despite their relevance, the scope of RBPs involved in virus infection remains largely unknown. We propose, here, a new strategy to identify in a global manner the subset of RBPs implicated in infection using the prototypical Sindbis virus as a model. In brief, we will label viral RNA with a nucleotide analogue called 4-thiouridine (4SU). Upon irradiation, with 365 nm ultraviolet light, 4SU is activated acting as a ""glue"" that covalently links the viral RNA to the proteins interacting with it. These chemically ""frozen"" complexes will be captured using oligo(dT) beads as a ""fishing net"". The proteins ""stuck"" to the viral RNA will be identified by proteomic approaches. The levels or activity of key candidates will be altered using genetic tools or drugs to assess their consequences in the infection of Sindbis virus and other human RNA viruses. RBPs with a strong influence in infection will be studied in detail to understand their biological role. Our approach will identify targets for new antiviral strategies.",,2022,N/A,110722.96,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,Unspecified,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2021 +P30394,10114137,Closed System Ultraviolet Germicidal Irradiation Reactor for Biological Pollutant Extraction and Neutralisation. (UVC-Reactor),"Biological pollutants include bacteria, moulds, viruses, animal dander and cat saliva, and pollen. Viruses are transmitted and bacteria are carried by people and animals. Dried, air borne protein in urine from rats and mice is also a potent allergen. Contaminated central air handling systems can become breeding grounds for these biological contaminants and can then distribute these contaminants into occupied spaces. The existing innovation is a closed system, air sterilisation unit which was developed during the later stages of the global COVID19 pandemic in 2021 with assistance from InnovateUK through a call for ""Systems to Combat COVID-19"" and subsequently through the European Regional Development Fund (ERDF) for the concept design phase conducted at the Sustainable Advanced Manufacturing centre, Sunderland University. A patent application was filled (UK Patent Application No 2107621.1) in 2021\. There is currently no international standard to determine the efficacy of air sterilisation units and quantifying their ability to destroy pathogens such as SARS-CoV-2\. Liverpool School of Tropical Medicine (LSTM), in conjunction with The Scientific Advisory Group for Emergencies (SAGE) trialled the first TRL9 Limited prototype UVC-Reactor in June 2023 in their Liverpool based Category 3 laboratories. Trials were conducted with live COVID virus from a patient at Royal Liverpool University Hospital. A clinical report was produced, which demonstrated 100% efficacy for the UVC-Reactor system compared to the control sample. The aim of this project is to conduct extended field trials to evaluate and enhance the UVC-Reactor solution for applications in the clean air domain. The technology focuses on monitoring, mitigating and extracting airborne pathogens and pollution. Field results from a real world environment and application will then provide insight and feedback from future users and customers to make final adjustments to the product that will lead to successful commercialisation. In parallel to the field trials, research at LSTM will enable testing for other pathogens such as measles, influenza and monkey pox, which will be integrated into the efficacy determination model.",,2025,N/A,105526.71,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2024 +P30396,BB/W509966/1,Optimising genomic RNA RNA interactions for development of flexible influenza virus vector backbones for co vaccination,"Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.",,2025,N/A,165037.93,Unspecified,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Unspecified,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",Vaccine design and administration,2021 +P30397,MR/S024468/2,Molecular regulation of NK cell functional maturation by the transcription factor BACH2,"Natural killer (NK) cells are a specialised immune cell type that form a critical first line of defence against cancer and infection. NK cells recognise cancer cells and infections in a different way to CD8+ T cells. This makes them attractive as alternate targets for immunotherapy. Clinical responses to NK cell-targeted immunotherapies have thus far been modest identifying a need to better understand molecular processes that restrict their function. NK cells exist in a variety of different states, called functional maturation states. These have important implications for their ability to control infections and cancer. We lack an understanding of how NK cell functional maturation is regulated, though identifying such mechanisms may provide new therapeutic targets in NK cell-based immune therapies. In people, genetic variations in a gene that encodes a transcription factor protein called BACH2 are associated with susceptibility to multiple autoimmune and allergic diseases, caused when the immune system undergoes excessive activation. Recent experiments conducted in our laboratories indicate that BACH2 is expressed in NK cells and negatively regulates their functional maturation with consequences for tumour immunity. The purpose of this work is to establish the function of BACH2 in NK cells, testing the hypothesis that it is a critical negative regulator of NK cell functional maturation and testing its consequences for homeostasis and immune responses to infection and cancer. Our proposed study is organised into three aims: Firstly, we will find out how BACH2 affects the behaviour of NK cells under normal conditions, and during infection with influenza, where NK cells can contribute to both viral clearance and excessive inflammation. Secondly, we will examine the effect of BACH2 in NK cell responses against cancer, both in NK cells existing within the body, and upon therapeutic transfer into tumour-bearing hosts. Finally, we will examine the molecular processes that underpin the function of BACH2, finding out where BACH2 binds in NK cell genomes and which genes it regulates. Collectively, this research will enable a better understanding of how the function of the immune system is controlled to under normal conditions and during infections and cancer. This may enable development of new therapies that work by either restraining or enhancing immune responses in individuals with inflammation, infections and cancer.",,2022,N/A,557422.69,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Immunity",2020 +P30400,MR/W018519/1,The mechanistic basis for the ZAP antiviral system targeting viral and cellular RNAs,"ZAP is an antiviral protein found in most vertebrates that restricts a diverse range of viruses by binding viral RNA to inhibit its translation into viral proteins and target it for degradation. A full understanding of how ZAP inhibits viruses can be used to develop new therapeutic applications. Introducing ZAP binding sites in viral RNA could increase ZAP-mediated inhibition to create new live attenuated virus vaccines. Another application is to introduce ZAP binding sites into viruses which selectively replicate in tumours to kill the cancer cells and trigger immune responses. Several types of cancer, including liver, colon and bladder, have lower ZAP expression than adjacent non-cancer tissue and this is associated with poor disease progression and survival. ZAP-restricted oncolytic viruses may be a good treatment for these types of cancer since they will replicate in the cancer cells more efficiently than the surrounding healthy tissue. However, to exploit these possibilities, we need a better understanding of how ZAP inhibits viral replication. First, it is unclear how ZAP selects which viral RNAs to bind to. Therefore, we will characterise how ZAP specifically binds target RNA and use this understanding to introduce optimal ZAP binding sites into viral RNA to increase their sensitivity to ZAP-mediated inhibition. Second, while ZAP interacts with many cellular proteins, only a few proteins are known to regulate its antiviral activity. To identify proteins that promote or inhibit its activity, we will use genetic screens based on a comprehensive list of its interacting partners. Third, it is unclear where in the cell ZAP acts to inhibit virus gene expression. We will use cutting edge microscopy techniques to visualise how ZAP inhibits a virus. While ZAP inhibits a broad range of viruses, for the purposes of this grant we will use three medically relevant viruses to characterise the ZAP antiviral pathway. We will analyse how ZAP inhibits HIV-1, whose worldwide spread has caused the AIDS pandemic and represents a straightforward system to analyse ZAP function; SARS-CoV-2, which causes COVID-19 and for which novel therapeutics are needed; and influenza A virus, which causes seasonal respiratory disease and periodic pandemics with severe disease and requires new vaccination strategies to be developed. Overall, understanding how ZAP inhibits viral replication will allow us to potentially develop these new therapies.",,2026,N/A,1242922.3,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease pathogenesis",2022 +P30402,BB/W020351/1,Understanding host interactions with high consequence pathogens using super resolution light microscopy in biocontainment.,"This research proposal is for a piece of laboratory equipment called a Cell Discoverer 7. This is a microscope that allows us to see within cells. This is vital because infectious diseases important to animal and human health, such as viruses, work inside cells, and we need to see how they work in real time in order to better develop mechanisms to stop them. This equipment is important for us as we want to use it to study infectious diseases that impact on human and animal health at Containment Level (CL3). Currently, to our knowledge, there is no such facility in government supported research institutes or Universities. CL3 is a way of working safely with dangerous pathogens that pose a greater threat to human and/or animal health. Examples include, SARS-CoV-2, certain influenza viruses, many infectious diseases that we get from mosquitoes and bacteria like tuberculosis (TB). Working at CL3 is not easy and the experiments you can do are limited by safety considerations. Currently the state of the art is that any images of infection are from inactivated specimens - this leads to distortion of images/pictures and no live work. The Cell Discoverer 7 has some unique features that allow a real step change and allow us to really advance our research on high consequence infectious diseases of humans and animals. This advanced microscope will allow us to follow the proteins and effects of infectious diseases in real time e.g., in living things. This latter feature is the really important one - as this has not been done before at high containment. We will be to determine whether therapeutic compounds are effective in stopping disease progression as well as identify fundamental parts of the infectious disease lifecycle that we could target in the future. Because of the unique features of this microscope and our ability to use it at CL3, we have many letters of support from Research Council/Government supported Institutes and Universities where we would act as a research hotel and training facility. This would really drive forward the competitiveness of UK science and more importantly allow us to deal with the infectious disease challenges that are on the horizon. These include zoonotic infections (diseases that we get from animals), vector borne diseases due to climate change (diseases that we get from things like mosquitoes) and studying anti-microbial resistance.",,2023,N/A,410626.92,Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Unspecified,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Clinical characterisation and management,Disease pathogenesis,2022 +P30405,10052824,A bright future: The use of Far UV as a disinfectant in the livestock industry-Feasibility studies in the dairy and poultry sectors,"Farm animal health and welfare has been described as a priority issue in discussions about the future of agricultural policy in the UK. Livestock diseases pose threats to the environment, animal welfare, public health and the economy. Only a limited number of measures developed to combat infectious disease in livestock have been successful and there is a need for more effective control measures. Ultraviolet (UVC) light disinfection systems have been used for many years, due to their efficacy in eliminating pathogens, but were previously unsuitable for direct exposure to humans and animals due to potential damage to the skin and eyes. Far UV technology operates at 222nm wavelength and does not reach live cells in the epidermis, hence does not cause negative effects, yet retains effectiveness in eliminating pathogens. Far UV is currently used in non-agricultural settings to disinfect public spaces and has shown efficacy against a wide range of viruses and bacteria including human coronaviruses, _Escherichia coli 0157_, Influenza viruses, Methicillin-resistant _Staphylococcus aureus_ and has been proven to reduce the overall bacterial count following exposure. Far UV has not been formally trialled in live animal agriculture in the UK and therefore presents a unique opportunity to investigate its possible uses in livestock disease control. Feasibility studies will focus on the dairy and broiler poultry sectors to represent ruminant and monogastric industries where endemic and epidemic diseases lead to major financial losses. The poultry study will focus on the lobbies from which barns are accessed. To assess whether disease transmission into barns can be reduced, Far UV devices will be deployed and environmental swab samples will be taken before and after Far UV exposure. We will also trial Far UV wands to disinfect footwear. In the dairy setting we will focus on calf housing disinfection potential. The efficacy of Far UV will be assessed by measuring microbial counts that also can be used as a proxy for efficacy against viruses: Recent research shows that viruses are more sensitive to deactivation than bacteria and can be eliminated at much lower doses of Far UV than what will be used in this study. This research presents a unique opportunity to develop innovative Far UV based disinfection methods effective against a range of pathogens, including multidrug resistant bacteria, and could form part of more effective disease control programs in the future.",,2025,N/A,336328.42,Animals | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,Unspecified,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Infection prevention and control,IPC at the human-animal interface,2023 +P30407,BB/W003325/1,"Protecting poultry from avian influenza, Newcastle disease, infectious bronchitis, and Gumboro disease with a single dose of a multivalent vaccine","Poultry is one of the fastest-growing sectors that is playing a major role in the provision of food security, economic development and poverty reduction. The demand for poultry meat and eggs has been increasing exponentially in recent years with the current annual population of poultry reaching over 50,000 million. This estimates that poultry production continues to grow by 24% in the next decade. However, the biggest threat in the sustainability of poultry production is the hyper prevalence of a multitude of infectious pathogens, such as different subtypes (H5, H7 and H9) of avian influenza viruses (AIV), Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) and infectious bursal disease virus (IBDV). An estimated production loss from these pathogens account for at least 20% in many regions around the globe. Primarily, the control against these diseases is achieved through vaccination. However, the effectiveness of most of the current vaccines is suboptimal, where they may only reduce the manifestation of clinical disease and mortality, but infected animals continue to shed viruses resulting in a continual chain of infections to susceptible naïve and vaccinated animals resulting in reduced weight gain in meat birds and reduced egg production and quality in layers and breeder flocks. For example, despite the hyper deployment of multiple repeated doses of each vaccine for each target disease, the manifestation of pathogens continues in the form of endemic prevalence and farmers continue to bear debilitating losses with sometimes up to 100% flock mortality or loss of egg production and zoonotic infection threats in the case of AIV. Current vaccines carry several inherent drawbacks including (i) one vaccine per disease which require multiple vaccinations and multiple bird handling resulting in expensive vaccination programmes; (ii) vaccines are given to chickens during the first three weeks of age, during this time period, birds carry maternally derived antibodies (MDA) which interferes with the vaccine performance and the efficacy of vaccines is reduced significantly; (iii) vaccines are produced in the eggs that are not ideal and requires replacement with cell culture systems; (iv) vaccines are not compatible for easy differentiation of infected from vaccinated animals (DIVA), therefore, disease-free status cannot be reclaimed easily in endemic disease regions. Therefore, new innovative vaccines are needed that could overcome these challenges. This proposal plans to address these challenges and to develop a multivalent vaccine formulation that offers protection to chickens from up to six major pathogens (AIV-H5, AIV-H7, AIV-H9, NDV, IBV, IBDV). This project will be built on our novel Target Antigen Delivery Vaccine (TADV) platform which selectively delivers vaccine antigens to chicken immune cells and potentiate antigen-specific immune response. Our studies have provided evidence that a single dose of our TADV vaccine containing modified haemagglutinin (HA) antigen fused to the antibody that specifically binds to chicken antigen-presenting cells (APCs) induced significantly faster, higher and more durable immune response in MDA positive chickens compared to the untargeted counterpart or the conventional killed virus vaccines. Here, we will use our TADV technology and develop a multivalent TADV formulation in which a single dose will contain up to six immunogenic antigens from different viruses including (AIV-H5, AIV-H7, AIV-H9, NDV, IBV, IBDV). This multivalent vaccine can be delivered to day-old chickens at the hatchery overcoming MDA inference and inducing highly protective immunity in vaccinated birds. Availability of such novel protective and cost-effective disease control tools and strategies should minimise the impact of infectious diseases on farm animals, and offer substantial indirect economic, public health, environmental and social benefits globally.",,2025,N/A,558373.58,Animals | Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Other,H5 | H7 | Other,,,,Unspecified,,Unspecified,,Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation",,2022 +P30408,2737654,Objectives matter: A mathematical modelling framework to identify optimal control strategies for future infectious disease outbreaks,"When deciding upon the optimal control intervention during an epidemic, a policy maker might seek to select the strategy that minimises a defined epidemic metric such as cost, duration or the number of severe disease cases. It is most likely, however, that the policy maker in question is required to consider multiple competing objectives which complicates the identification of the optimal strategy. The decision is further complicated by uncertainty, especially if the pathogen is novel and disease-specific parameters or the efficacy of interventions are unknown. The policy maker could therefore benefit from a framework which can recommend control strategies for future infectious disease outbreaks, subject to a cost function which includes multiple objectives. This project aims to develop a mathematical framework which uses a suitable objective function to explore optimisation of control interventions for infectious disease outbreaks. The project will use the framework to investigate how optimal intervention policies are dependent upon the spatiotemporal state of the outbreak, the characteristics of the disease and, crucially, the objective of policy makers when implementing such policies. This framework will be initially applied to models of respiratory virus outbreaks in humans of global significance, such as seasonal influenza. Time permitting, the framework will be extended to consider animal or plant diseases which may require an alternate modelling approach and a different class of control interventions. The project will rely upon the development and simulation of various models of infectious disease outbreaks whose projections will be used to measure the objective function against. The models must be developed to allow for flexible implementation of feasible control interventions and will be fitted to data (either provided by the external partner or publicly available through previous publications and/or online public health dashboards) using statistical inference, or incorporate plausible uncertainty in disease parameters such as the transmission rate to investigate changes in the objective function. We will develop a suite of models that can be used in a range of different future infectious disease outbreaks, including considering stochastic models and spatially explicit models. In the case of respiratory diseases, considering a spatially explicit model adds a layer of realism to the modelling as restrictions during the recent SARS-CoV-2 (COVID-19) pandemic were often localised. This can assist the policy maker in identifying vulnerable administrative divisions and taking targeted action. In the context of plant and animal diseases, the spatial heterogeneities are essential for model accuracy as the population can no longer be considered to be well-mixed.",,2026,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,,,,,,,,,Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies | Infection prevention and control,Impact/ effectiveness of control measures | Restriction measures to prevent secondary transmission in communities,2022 +P30412,MR/V000659/1,Lung resident memory CD8+ T cells during viral infections - generation and functionality regulated by localisation and type I IFNs,"According to the World Health Organisation, lung infections kill ~3 million people each year, more than twice the number that die of diarrhoeal diseases, AIDS and diabetes combined. Viruses are responsible for many of these infections, but there is relatively little research investment in discovering how upper respiratory viral infections spread to the lungs and cause pneumonia. The most common viral causes of lower respiratory tract infections are respiratory syncytial virus (RSV) and influenza A virus (IAV), both frequently causing severe disease. Despite a vast effort over six decades, vaccines that elicit protection against RSV are yet to be developed. There are partially effective vaccines against IAV, but they need to be redesigned each year to match the new strains of IAV that constantly evolve. Most vaccines are given as an injection and induce protective antibodies that circulate in the bloodstream. As such, they are not optimised to specifically protect the lung or to mobilise lung-resident immune cells that help protect from severe disease. Our understanding of how lung-resident immune cells defend us against respiratory viruses is incomplete, but recent evidence shows that a special subset of T cells, known as tissue resident memory T (Trm) cells, are critical for rapid elimination of viruses such as RSV and IAV. While it is likely that the environment in which these cells reside shapes their function and life span, it remains unclear how this happens. We believe that Trm cells are maintained in specific niches within the lung where they are nurtured by interactions with neighbouring cells. During viral infection, essential anti-viral molecules called type I interferons (IFNs) are produced in large quantities. These cytokines can alter how T cells behave but their role in determining the function of Trm cells is not known. In this proposal we will study how type I IFNs affect the behaviour of Trm cells. To achieve this, we will use a new technique in which we study live slices of lung tissue in culture. These living slices can be re-stimulated with virus or components of the virus in the lab to enable detailed visualisation of tissue-resident cells and their responses. We will compare slices from mice and humans, investigating how type I IFNs influence Trm cells; their survival, function and localisation. Thus, this proposal will provide increased understanding of how tissue-protective T cells are regulated, which will help the development of new vaccines and treatments that harness the potentials of Trm cells to alleviate viral induced disease.",,2024,N/A,841635.4,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2021 +P30413,2881660,Modelling the disorganised ecology of post-pandemic respiratory viruses,"Prior to the COVID-19 pandemic, the circulation of respiratory viruses during the winter was relatively predictable. However, outbreak control measures implemented throughout the pandemic have thrown regular seasonal patterns into disarray. After historically low circulation of seasonal respiratory viruses like influenza and respiratory syncytial virus (RSV), they have returned, characterised by unusual transmission. Various factors may be contributing to this phenomenon, such as the lack of exposure to these viruses during the period of heavy restrictions. Those that would have normally been infected would have gained immunity, protection from infection. However, with most seasonal respiratory viruses, immunity is not lifelong, meaning that after a certain period there is the potential for reinfection, thus creating patterns of infection. This PhD project will use the disruption to usual seasonal circulation of respiratory viruses, caused by the COVID-19 pandemic, and the following reorganisation of these viruses to better understand how they circulate in the environment and how circulation patterns are created and maintained. This project will use publicly available data on respiratory infections from the UK Health Security Agency (HSA). In addition, the possibility of using publicly available European datasets hosted at the European Centre for Disease Prevention and Control (ECDC) for analysis will be considered with the supervisors. An analysis on historical circulation of the viruses of interest will be done so that it can be compared to current circulation and during the ""pandemic years"". Mathematical models will be designed and developed to investigate biological or sociological reasons for changes in post-pandemic seasonal respiratory virus circulation. The research method will significantly contribute to the development of quantitative skills. In addition, the approach to the research question will be multidisciplinary since elements of public health, virology, and immunology as well as statistics and computer programming will be considered. Therefore, depth of knowledge will be obtained on infectious disease modelling and breadth of knowledge will also be acquired due to the nature of the research and the working environment. This project offers an opportunity to better understand the drivers of seasonal respiratory virus transmission. This knowledge can be useful to establish strategies to mitigate the impact of respiratory virus infections, reduce their burden on the population and alleviate the strain they put on healthcare systems. The work from this project will be useful to governments and public health; equipped with more knowledge they can provide better guidance and advice as well as design more effective and targeted future interventions.",,2027,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Indirect health impacts,2023 +P30417,2572390,Development of electronic devices for virus detection applications,"The seminal importance of detecting virus pathogen at point-of-care tests has driven the search for more sensitive, low-cost, scalable, and robust sensors. The mass and economical production of efficient detection devices for viruses, bacteria and other pathogens can play a crucial role in facilitating early diagnosis and mitigation of diseases. Specifically, for the SARS-CoV-2 virus, effective detection techniques have played a significant role in containing the spread of the highly infectious disease. The gold standard method currently employed for SARS-CoV-2 detection is real-time reverse transcription polymerase chain reaction (RT-PCR) [1, 2]. However, this molecular diagnosis method is expensive, time consuming and inconvenient, requiring highly trained professionals to conduct tests [2]. Therefore, there is an urgent unmet need for point-of-care diagnostic techniques that are accurate, rapid and inexpensive. The aim of this project is to study the materials, devices and the electronic phenomenon in biological and electronics world in order to develop an efficient, low-cost, robust, compact and rapid immunodiagnostic testing device, specifically the electronic devices i.e., field effect transistors and electrochemical transistors. These devices may contain pathogen binding aptamers or antibodies in an electronic polymer matrix in their active channels or metal electrodes. The target is to detect pathogens such as respiratory infection causing viruses (influenza, RSV, COVID) in the FET channel and study the electro-capacitive transient signature for each pathogen. The device design will further include i) multiplexing to diagnose viruses on the same chip and ii) artificial intelligence feedback loop to the sensor for improved accuracy of the device. An extensive study will investigate the bio/chemical changes in device upon exposure to the pathogens, aiding in the formulation of a relationship between the detection mechanism, material combination and their interfaces. In this project, a multitude of device fabrication and geometry concepts will be explored at the Department of Engineering, Durham University. The direct channel analysis of saliva and blood samples will be performed at the Lancaster University, in collaboration with specialist virologist Dr Muhammad Munir and his research group. Dr Munir is also supporting the project with free access to their lab, materials and travelling to Lancaster. CPI-Sedgefield has a deep interest in the printable sensor technology for point-of-care diagnostics and therefore has a platform for prototype development and would be interested in supporting further funding bids and commercialisation, if the project is successful. To summarise, the project addresses the challenges in development of novel transistor-based biosensors that enables highly sensitive and selective, miniaturized point-of-care detection technology. References: [1] Morales-Narváez, E. et al. Biosensors and Bioelectronics, 163, 112274, 2020. [2] Poghossian, A. et al. Frontiers in Plant Science, 11, 2020. [3] Seo, G. et al. ACS Nano, 14(4), 5135, 2020.",,2025,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Diagnostics | Pathogen morphology, shedding & natural history",2021 +P30418,2606805,Social and psychological determinants of vaccination uptake - Linking attitudinal and behavioural data to policy analysis and implementation,"Suboptimal coverage in vaccination programmes remains a global health priority. Every year 60 million frail adults in the EU are not protected against influenza by vaccination. Flu epidemics can cause between 500,000-1,000,000 deaths globally. The World Health Organisation recently concluded that high-quality behavioural research linked to policy-making and broad partnerships are essential to tackle this challenge. The ongoing COVID19 pandemic is likely to exacerbate some concerns about vaccination in general and about flu vaccination in particular (as they are both respiratory viruses), with anti-vaccination coverage already present in some media. This project offers such a novel partnership between academia, the vaccine manufacturing industry, and policy-making, grounded on social science methods. The project will apply implementation science concepts, which is a relatively new multidisciplinary field aiming to accelerate the translation of research findings into health services and policy (in this case, aiming to increase flu vaccination coverage). Following literature review, the project will firstly deliver a comparative 'gap analysis' between population-level concerns around vaccination for flu (as 'exemplar' vaccine) and what national vaccination policies and supporting campaigns focus on. The UK and Germany are the two countries of focus for the research. Next, the project will address these gaps (wherever found) - at structured workshops with policy design and implementation stakeholders. The outputs of these workshops will be novel vaccination policy/campaign briefs informed by behavioural evidence and co-designed by scientists, policy-makers, advocates and other stakeholders. Finally, the project will produce short versions of previously developed detailed surveys that measure attitudes towards flu vaccination. Statistical methods will be used to derive short versions of those surveys, which will be easier to implement at scale by policy-makers. The project is stakeholder-driven and sensitive to the ongoing COVID19 pandemic. We will thus seek to apply lessons from the well-developed attitudinal evidence base on the flu vaccination to potential concerns about a COVID19 vaccine (when one becomes widely available). We will further consult with stakeholders (which is a core phase of the proposed research) to apply the proposed methods to both the seasonal flu and the COVID19 vaccination programmes if the global pandemic context necessitates this approach. We have already started this translational process: the student and supervisor of this research have just published one of the first, to our knowledge, attitudinal studies of a COVID19 vaccine in the UK, informed by the theoretical and empirical evidence base on flu vaccination acceptance. This flexibility allows the proposed doctoral programme to flexibly adapt and effectively respond to both pandemic need and the need for ongoing successful flu immunisation in the UK and globally in the coming 3 years.",,2024,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Policies for public health, disease control & community resilience",Approaches to public health interventions | Vaccine/Therapeutic/ treatment hesitancy,2021 +P30419,BB/X017281/1,"The role of B cell - macrophage interactions for adaption to virus escape, memory, and immune tolerance","Vaccination induces antibodies that protect us from infection for many years. The same happens during infection. We try to understand how our immune system is able to custom design antibodies that can exactly fit to any random infectious agents we might come into contact with. Antibodies are generated by B cells. The process of B cells adapting to foreign structures on infectious agents happens in lymph nodes and is called B cell affinity maturation. Affinity maturation takes several weeks, which is why vaccination takes weeks to fully protect us. We recently found that another cell type is important in the process of B cell affinity maturation: phagocytic ""eating"" cells that can filter and eat infectious agents in the lymph and blood stream. These phagocytes can transfer what they see to B cells, and in this way alert B cells of any new threats emerging. We found that the first thing B cells do after affinity maturation is to interact with phagocytes. It seems that B cells test whether they recognise any of what the phagocytes are carrying. We think this is a very important 1st check to test whether freshly affinity-matured B cells are useful in the long term. In the current project we plan to better characterise what exactly happens during the interaction of phagocytes and B cells. Which signals can and do phagocytes transfer to B cells? Further, we want to test why this interaction is so important. We think there are several possible explanations: 1) The interaction of phagocytes and B cells can alert B cells that the infectious agent has mutated. This is common in virus infections, e.g. the Covid-19 virus, influenza, or HIV infection. 2) Phagocytes may tell B cells that the infectious agent is still around and instruct them to keep going with affinity maturation, making affinity maturation more efficient. 3) The interaction may alert B cells that they react with structures that are part of the healthy body - self. These self-reactive B cells must be deleted or instructed to affinity-mature away from self-reactivity in order to prevent illness from self-reactive antibody. 4) The interaction may be important to quickly instruct B cells to make protective antibodies. We plan to test all these possible scenarios. The project should lead to understanding how our immune system deals efficiently with infection and vaccination, how we deal with virus mutants and why during the process we do not become autoimmune to ourselves. Apart from answering these basic questions of biological process, understanding them should help to generate better vaccines or drugs that stimulate our bodies' immune response to infectious agents.",,2026,N/A,851671.72,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Unspecified,,,,,,,,,Unspecified,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Immunity,2023 +P30420,2606553,The role of UpA dinucleotides in regulating virus replication,"What does the genetic make-up of RNA viruses look like? All genomes are composed of four bases, A, C, G and T (or U in the case of viral RNA genomes and mRNAs). If these were selected randomly, every genome would comprise 25% of each base; but this is not the case. Similarly, there are 16 possible combinations of nucleotide pairs, or dinucleotides. With random representation, each dinucleotide would occur 1/16 or 6.25% of the time, but again this is not so. In the genomes of all organisms, from bacteria to humans, TpA dinucleotides ('p' represents the phosphate bridge in the DNA backbone) are under-represented. We don't know why this is. Even more intriguingly, RNA viruses mimic this by suppressing UpA in their genomes. When a virus infects a host cell, this triggers an interferon response that results in hundreds of antiviral genes being upregulated. One such gene is RNaseL. In 1981 it was reported that mRNA is cleaved at UpA motifs by RNaseL. This offers one possible explanation for why UpAs are suppressed in the genomes of viruses and their hosts. However, when UpAs are added into virus genomes, the virus is impaired, but depletion of RNaseL from the system does not remove the impairment, suggesting other factors are at play. Alternatively, UpAs may be avoided to reduce the risk of introducing stop codons. Two of the three stop codons (UAA and UAG) include UpA motifs, and if UpAs are deselected the chances of aberrantly introducing stop codons in protein coding sequences are reduced. The purpose of this interdisciplinary project is to integrate computational (Lycett lab) and laboratory (Gaunt lab) based methods to characterise the distribution of UpAs in RNA virus genomes, and establish their importance in a virus system. Specifically you will: 1. Determine the distribution of UpA motifs in selected RNA viruses by assessing whether their frequencies are different in coding and non-coding regions, whether UpAs occur within or across codon boundaries, and whether they correlate with the occurrence of stop codons or are utilised / deselected under different pressures. 2. Use this understanding to design and synthesise mutants of influenza A virus with increased UpA content, and characterise the impact of UpA introduction on virus replication. You will test whether removal of RNaseL (and other factors) from the system abrogates the anticipated defect in virus replication. 3. If RNaseL restricts virus replication, you will characterise the mechanism. If RNaseL is not restrictive, you will use a small screen based approach to identify cellular factor(s) that are important for UpA recognition by the host cell. From this project, you will learn data science skills, applied to biological data - including statistical, bayesian, machine learning and evolutionary modelling, (bio)informatics, phylogenetics and phylodynamics, as well as computing skills including how to code, script and use high performance computing; and laboratory skills including how to perform virus infections and virology assays, and molecular biology techniques including CRISPR.",,2025,N/A,,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Unspecified,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2021 +P30423,BB/W00884X/1,Exploring the Factors that Determine the Survival of Viruses in Aerosols and Droplets,"The transmission of microbes which cause disease between humans, such as bacteria and viruses, can occur by direct (person-to-person), indirect (contact with contaminated surfaces) and airborne routes. Small aerosol particles of a respirable size (<10 micrometres diameter) and larger droplets (up to 100 micrometres, about twice the diameter of a human hair) can remain airborne for minutes to hours and are emitted by coughing, sneezing, speaking and breathing. Larger droplets settle very quickly over short distances contaminating surfaces (referred to as fomites). Although the transmission of some diseases, such as tuberculosis and measles, show preferential airborne transmission, other diseases, such as influenza and norovirus, are opportunistic. Identifying both the circumstances when these different modes of transmission are dominant and clarifying ways to mitigate them must be priorities. Such knowledge informs the implementation of non-pharmaceutical interventions, such as physical distancing and the use of appropriate personal protective equipment such as face masks. Further, the clinical context sees the wide use of many aerosol generating procedures that are poorly understood but could carry pathogens through the air, for example in dental procedures and in anaesthesia. Despite the recognised importance of aerosols and droplets in the transmission of microbes, the evidence-base on which decisions are made to mitigate microbe transmission often remain epidemiological. Robust innovative instruments for studying the factors that control the survival of pathogens in aerosols, droplets and fomites are crucial to move our understanding forward. Using a novel technology platform developed at the University of Bristol, we will deliver a comprehensive framework for understanding the factors that control the survival of the virus SARS-CoV-2, the cause of COVID-19 in aerosols, droplets and fomites. We have developed a bespoke system to study how well microbes survive in aerosols and droplets containing microbes referred to as CELEBS. We will study the interactions between the SARS-CoV-2 virus (in respiratory droplets) and its immediate environment in a recently commissioned state of the art facility. By levitating a known number of aerosol droplets of identical size with a known viral load for a specified period of time, the survival of the virus will be measured and the impact of inactivation measures studied. More specifically, we will fully explore the survival of the SARS-CoV-2 virus in droplets of varying size exposed to varying environmental conditions (relative humidity and temperature) and in realistic simulated fomites deposited on surfaces. We will also explore the influence of light and atmospheric oxidants (open air factor) and the rate of dynamic changes in particle size and moisture content upon droplet/aerosol generation (i.e. desiccation/drying kinetics on exhalation). The survival of different variants of the SARS-CoV-2 virus will be examined. This project will build on preliminary work that has confirmed and validated our experimental approach. This more comprehensive work will provide clarity to inform non-pharmaceutical interventions such as social distancing, recommended indoor operating temperatures and humidities (e.g. hospitals, care homes, transport) and other methods of inactivation (e.g. light and oxidants). Extending beyond these immediate studies, the technique will be flexible, opening up opportunities to study a wider range of important airborne pathogens.",,2025,N/A,734579.18,Viruses | Environment,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Other,,,,,,,,,COVID-19 | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics",Environmental stability of pathogen,2022 +P30426,2578241,The impact of Vitamin D supplementation on immune responses to respiratory pathogens in older children in Zambia with perinatally-acquired HIV-1,"The purpose of this project is to assess whether vitamin D supplementation improves immune responses to respiratory pathogens in children living with HIV (CWH) in Sub-Saharan Africa. This study will be embedded in a larger ongoing vitamin D intervention trial in Zambia. Sub-Saharan African children are disproportionately affected by the global HIV epidemic. Of the two million children living with HIV globally, 90% reside in Sub-Saharan Africa. Despite the roll-out of antiretroviral therapy (ART), HIV and its associated comorbidities remains one of the leading causes of death among children in Sub-Saharan Africa. While ART has greatly improved this cohort's survival into adolescence, these individuals continue to suffer from chronic comorbidities, principal among which are severe and recurrent respiratory infections. It is believed that a major contributor to this problem is vitamin D deficiency. CWH in Sub-Saharan Africa tend to have very low levels of vitamin D, and this has pleiotropic effects on health with major adverse effects on immune function. Additionally, in other settings, vitamin D deficiency has been established as a well-recognised contributor to poor outcomes in respiratory infections. It has therefore been hypothesised that vitamin D supplementation in CWH (alongside ART) will have wide-ranging health benefits, including a reduction in susceptibility to respiratory infection. This hypothesis is being tested in the EDCTP-funded VITALITY trial, a large ongoing study of weekly high-dose vitamin D3 supplementation in adolescents with perinatally acquired HIV-1 in Zambia and Zimbabwe. The proposed project will form a sub-study within VITALITY, testing the hypothesis that vitamin D3 supplementation improves immune responses to respiratory pathogens. To do this, the following parameters will be measured: 1. Soluble and Cellular Markers of Immunity Samples from the VITALITY trial will be evaluated for both cellular and soluble markers of immunity. Tests of T-cell immunity will include flow cytometric assessment of T-cell subsets such as TH1, TH2, TH17 and T-Regulatory cells, and evaluation of changes in CD8+ and CD4+ T-Cell activation. Soluble markers will be investigated using a multiplexed approach to identify proinflammatory markers in patient samples. In vitro stimulation assays will be conducted to test pathogen-specific responses to bacterial pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis, and viral pathogens such as Influenza A, RSV and in selected cases SARS-CoV-2. 2. Allelic Variants in the Vitamin D Pathway It has been shown that allelic variants in the vitamin D pathway are associated with increased risk to respiratory infection. As a result, patient samples (n=420) will be retroactively stratified by genotype to determine if response to treatment varies according to variants at vitamin D associated genes. This information will furthermore be used to determine the impact of genotype on clinical response to vitamin D therapy. The findings of this work will demonstrate whether vitamin D supplementation improves protective immune responses to respiratory diseases in this at-risk population. Likely mechanisms will be elucidated leading to a better understanding of how mediators such as vitamin D modulate immunity. Given ongoing respiratory epidemics, and novel respiratory virus pandemics such as COVID-19, the findings of this study could address an unmet clinical need by providing an inexpensive and easily scalable treatment to improve health outcomes for CWH. Through this project the student will develop a range of skills including lab-based skills, statistical skills and associated computational skills, experience in translational research, and the experience of working on-site at a large clinical trial in Lusaka, Zambia.",,2025,N/A,,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae | Other,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management",Immunity | Disease pathogenesis,2021 +P30429,MR/W028433/1,MICA: Investigating mRNA encoded growth factor to promote epithelial repair in pulmonary fibrosis.,"Fibrosis of the lung is the gradual replacement of alveolar of air sacs with scar tissue that prevents the organ from carrying out efficient gas exchange and currently has no cure. Lung fibrosis can occur as a result of chronic disease such as idiopathic pulmonary fibrosis (IPF) or severe epithelial injury during respiratory infection. There are 6000 new cases of IPF each year in the UK, it is increasing in incidence and survival is only 3-5 years after diagnosis. Fibrosis remains one of the largest threats to health after recovery from COVID-19 and influenza. There is an urgent and unmet need to develop new therapies that can alter the progression of fibrosis. Repeated lung injury and an inability to repair properly play a central role in lung fibrosis, suggesting that repair processes could be important targets for therapy. Epithelial basal cells (BCs) are adult stem cells of the lung that can self-renew or differentiate to all types of lung epithelium after injury. They normally function to repair lungs efficiently, however recent studies suggest that basal cell function might be impaired in fibrosis. Further investigation is required to understand whether these cells can be manipulated to control how they function. Growth factors play an essential role in coordinating growth and regeneration of lung tissue. Fibroblast growth factor 7 (FGF7) binds specifically to FGF receptor 2-IIIb (FGFR2b) expressed only on epithelial cells including BCs to promote growth and differentiation. FGF7 has been shown to be dysregulated in lung fibrosis, as a result there is interest in supplementing FGF7 to promote repair and reduce fibrosis in the lung for disease modifying therapy. Delivery of FGF7 protein after lung injury in human and animal models has demonstrated its powerful influence on lung repair but it's use has been hindered because it must be delivered by intravenous injection which results in rapid elimination from the body, poor distribution to the lung and high toxicity. Synthetic messenger RNA (mRNA) is an emerging technology that instructs the body's own cells to produce a specific protein with transformative potential for how growth factors are applied clinically. Growth factors encoded by mRNA are being tested for heart and skin repair in humans but has never been attempted for the lung, partly due to challenges in delivery. We have previously developed materials to protect synthetic mRNA and facilitate its delivery into lung cells following nebulised delivery. This proposal will bring together our experience in mRNA delivery, with expertise in lung repair and fibrosis to investigate mRNA encoded growth factors as a novel strategy to guide lung repair after injury. In order to achieve our goal, we aim to address three key questions: 1. What is the influence of FGF7 mRNA on survival, proliferation and migration of human basal cells from normal and IPF lungs? 2. Can FGF7 mRNA promote differentiation of basal epithelial cells in human lung organoids? 3. Does local delivery of FGF7 mRNA reduce fibrosis and improve lung function following injury in a murine model? The outcomes of our research will be instrumental for the application of synthetic mRNA as a platform for protein production in the lung that could be broadly applied to different protein targets and will bring this pioneering technology closer to improving human health.",,2026,N/A,688837.87,Animals | Other,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Clinical characterisation and management | Therapeutics research, development and implementation","Supportive care, processes of care and management | Prophylactic use of treatments",2023 +P30432,2887265,"Pathogen pollution in critically endangered vultures in The Gambia, West Africa","The Gambia is home to seven vulture species, of which six are under threat of extinction: four critically endangered and two endangered. As scavengers, vultures provide crucial ecological services through devouring carrion and carcasses, thereby cycling nutrients and eliminating potentially harmful pathogens from the environment. This may mitigate spread of diseases, with impacts across local food webs and knock-on effects to human health and economies. Critically endangered hooded vultures (Necrosyrtes monachus), the focal species of the project, maintain a strong population in the Gambia despite continental decline. These birds are commensal with humans in the country, living in and around settlements. In this shared space, it is likely both humans and vultures are exposed to a similar suite of pathogens, including from livestock and other shared food sources. Despite strong immune systems, vultures are still susceptible to diseases of conservation and public health concern, such as avian influenza. Vultures have also been found to carry antimicrobial resistant bacterial pathogens. Understanding pathogen community ecology in hooded vultures and other vulture species, could not only guide efforts for the conservation of threatened keystone species, but sentinel for emerging zoonoses, threats to livestock health and provide a bioindicator for AMR. The 'One Health' approach emphasises interconnectivity between human, animal and environmental health, using cross-sectoral collaboration and integrated methods to combat global threats to each of these areas. Global vulture decline, and potential consequences of their loss, exemplifies the need for a One Health approach to zoonotic disease issues. Gambian vultures are already the subject of transdisciplinary research, including population monitoring, genetic, and parasite diversity studies. This project aims to expand this remit to include pathogen community ecology, exploring pathogenic threats affecting the health and conservation status of Gambian vultures, as well as the role these birds play in human health challenges. The transdisciplinary nature of the project lends itself to many routes of exploration - at this early stage, this is a non-exhaustive list of focus areas: 1. Pathogen community ecology of hooded vultures and other vulture species in the Gambia 2. Potential sources of pathogen pollution in the environment. 3. Risk of zoonotic and reverse zoonotic disease transmission between vultures and humans. 4. The role that vultures play in human, domestic and wild animal, and environmental health, through ecosystem service provision 5. The impact of pathogenic threats and environmental pathogenic pollution on hooded vulture populations, and if needed identification of mitigation strategies to aid conservation efforts. 6. Local knowledge, perceptions, and sociocultural value of vultures in the Gambia Part of the OneZoo Centre for Doctoral training, and supported by UKRI through three research councils - BBSRC, MRC, NERC, this project aligns with these bodies' key strategic challenge areas: ""bioscience for an integrated understanding of health""; ""global health"" and ""infections and immunity"" research; and ""ecology, biodiversity and systematics"", respectively. Skills necessary for this project to succeed align with UKRI priorities and will come from a variety of disciplines. These include: - Ecological skills - field work, including collection of biological and environmental samples and population monitoring - Molecular biology skills - PCR, DNA sequencing, serological analysis etc, for the identification and quantification of pathogen species, as well as exploration of genetic diversity and structure in vulture populations - Social science skills - exploration of sociocultural perspectives - Statistical and data science skills, including bioinformatics Keywords: one health, vultures, ecosystem services, zoonoses, pathogen pollution, conservation",,2027,N/A,,Animals,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae | Novel Pathogen,Unspecified,,,,,,,,Pandemic-prone influenza | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Animal and environmental research and research on diseases vectors | Pathogen: natural history, transmission and diagnostics",Animal source and routes of transmission | Vector biology | Environmental stability of pathogen,2023 +P30436,MR/W030454/1,Does maternal immunity to SARS-CoV-2 protect against SARS-CoV-2 infection in infants under 12 months old in Scotland?,"COVID-19 disease in children is generally less severe than in adults, most children with the COVID-19 virus (SARS-CoV-2) have mild or no symptoms. However, among children with SARS-CoV-2 infection, younger infants are at greatest risk of severe illness. Current COVID-19 vaccines are not approved for use in children under 12 years old in the UK, and any future child vaccine programme would still not protect the very youngest infants. Maternal immunity to infection is important in protecting infants against infectious diseases, including tetanus, pertussis and influenza. Young babies can be protected by antibodies which pass from mother to baby through the placenta, or through breast-milk. In addition, if a mother is immune to a virus, she may be less likely to catch it and pass it on to her baby. We know that COVID-19 antibodies from mothers can be transferred to babies in the womb and in breast milk. We don't yet know how well those antibodies might protect infants against SARS-CoV-2 infection, or whether vaccinating mothers reduces the risk of infection in their babies. This added benefit would make vaccines more cost-effective, and might encourage more women to be vaccinated. As the pandemic continues, and the time between initial vaccination and pregnancy increases, this study might also help decide whether a booster vaccination in pregnant women would be useful. It would also help us predict how many infants might be infected over time as more mothers become immune. We want to know how effective maternal COVID-19 vaccines are in protecting infants against SARS-Cov-2 infection, and whether maternal COVID-19 immunity, from either vaccination or prior infection, can reduce the risk to babies. To answer these questions we will undertake two studies. The first study will include babies born in Scotland between 1st August 2021 and 31st July 2022. Using NHS surveillance data, we will identify which of these infants have laboratory-confirmed SARS-CoV-2 infection before their 1st birthday. Using birth, death, GP records and surveillance data, these infant ""cases"" will be matched to ""controls"", infants born within one week of the case, who did not have a positive SARS-CoV-2 test before their 1st birthday. We will then link these infants to maternal records, and use routinely collected NHS data, including maternity records, vaccination records, SARS-CoV-2 testing data, to compare the two groups. We aim to include all cases that year, matched to at least 4 controls. Our key objectives will be to compare the odds of maternal vaccination, or prior maternal COVID-19 infection, in infants with and without confirmed SARS-CoV-2 infection in the first year of life. We will also look at other factors which might change the risk of SARS-CoV-2 infection including gestation, maternal age, ethnicity, deprivation, and urban/rural location. In the second study, we will identify cases and controls as above, but limited to infants born within NHS Greater Glasgow & Clyde healthboard. Using blood left over from maternal antenatal screening for infectious diseases, we will be able to measure maternal COVID-19 antibody levels druing early pregnancy. We will aim to collect samples from mothers of 500 cases and 1000 controls. We will then determine whether the presence of maternal COVID-19 antibodies (either from vaccine or natural infection) is associated with reduced risk of infection in their infants. For both studies all patient-identifiable data will be managed within the NHS Safe Haven and use approved processes of pseudo-anonymisation to ensure patient data are kept private. Individual patients will not provide consent, but use of this data for public benefit will be approved by ethics and privacy committees. These studies will help us understand how maternal COVID-19 immunity can help protect infants. This will help us plan vaccine programmes, and help inform vaccine choices for women in Scotland and elsewhere.",,2025,N/A,282272.49,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Vaccines research, development and implementation | Clinical characterisation and management","Characterisation of vaccine-induced immunity | Supportive care, processes of care and management",2022 +P30438,MR/X012565/1,Advanced tandem quadrupole mass spectrometer with an automated sample extractor for a multiuser interdisciplinary translational research facility,"There have been billions of pounds spend in research on new tests for diseases (biomarkers) but only a handful have made it to clinical use. The reasons are that there is often a lack of direct clinical question asked by research labs studying biomarkers and often a lack of robust method development and validation such that it can be used clinically. The van Geest Multi-OMIC facility is a world leader in the discovery and translation of biomarkers. We, in joint partnership with the University Hospitals of Leicester have developed the National Centre of Adherence Testing (NCAT), for assessing whether patients are adhering to their prescribed medications. This work has had impact not just on patient outcomes and international guidelines but to the design of clinical trials. The van Geest Multi-OMIC facility participated in the DHSC Moonshot Project. This national programme established a framework for rapid development, validation and implementation of a triple quadrupole mass spectrometer (LC-MS) method for the SARS-CoV-2 virus in swabs. The programme took about 5 months to develop a valid method for use clinically. The LC-MS instrument is state of the art and was provided with minimal fee for a year by the manufacturer Waters and is on site in our laboratory. LC-MS have exquisite levels of sensitivity and incredible levels of ability to identify only the protein of interest (specificity). An example of this is the use of LC-MS in identification of doping by elite athletes. Before samples can be loaded on the LC-MS they need to be prepared. These manual steps of purifying and isolating are slow and can lead to errors. Therefore, in this proposal we are requesting also an Agilent Bravo liquid handling unit to enable us to do a wide range of sample preparation approaches in a swift, reproducible and robust manner. We request the purchase of the above LC-MS to develop four main clinical projects that can be translated into clinically relevant assays using lessons learnt from the Moonshot programme and NCAT. The equipment offers very good value for money as it is being offered at a 53.5% discount by Waters. The first project is to develop a method that can detect multiple viruses seen in the winter such as influenza and Covid-19- in a rapid and scalable manner. We can also use MS to identify variants of viruses and look to see whether this can be used in determining viral persistence in Long COVID. The second project will deliver vastly improved methods for NCAT. It will reduce analysis time from 80 minutes to between 45 seconds to 3.5 minutes. Currently, due to the time taken, the method is available mainly for hypertension clinics. The new methods will enable the use to be expanded to other conditions including heart failure and rheumatoid arthritis, in hospitalised patients and those seeing their GP. We will also develop capabilities to study large research populations and the tailoring of medications according to an individual's medication blood level. The third project will lead a pioneering effort to develop ten methods to study a key pathway in blood pressure regulation- the renin-angiotensin aldosterone system (RAAS). These methods will help understand subgroups of hypertension and response to medications. The fourth project will allow remote patient monitoring of patients with long term conditions such as diabetes, thyroid disease and heart disease. Patients will self-collect their blood by finger prick, and we will develop methods for measurements of routine tests such their liver and kidney function. Successful completion will help provide robustness in patient management remotely- especially during future pandemics and free resources both in patient time and of the NHS. These projects are exemplars of the type of project that will enable us to swiftly validate and gain accreditation for assays that can then be taken straight into NHS laboratories.",,2023,N/A,355879.79,Human Populations | Other,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management","Diagnostics | Post acute and long term health consequences | Supportive care, processes of care and management",2022 +P30439,MR/Y001559/1,The IMMaged study: understanding the balance of immunity and immune disease in an aged immune system,"Our immune systems change as we get older, resulting in weaker protective responses to vaccines and infections and at the same time increasing 'autoimmune' responses in which the body reacts against itself, causing unhelpful inflammation or disease. We know these changes occur, but not what makes them happen or how we might improve them when they do. A better understanding of immune ageing could allow us to design better vaccines, identify who needs them most or better treat inflammatory disease in older people. To understand how the immune system works differently in older people, it is first necessary to describe the changes occurring: in other words, to find out what 'normal' ageing looks like. As part of an international effort, we have carefully collected and measured many different aspects of the immune system in thousands of people to describe what changes occur. This included measures of different cell types and protein levels in the blood alongside levels of protection against infection and against the body's own proteins (the 'autoreactive' responses). From this study we found that immune ageing occurred much more rapidly after 70 years of age and also changed at different rates in different people. This meant that people of a given age could have very different immune ages. We also found that their immune age was linked to their lifespan, suggesting that immune age might be critical for keeping us healthy in later years. Of all the immune changes we measured, only a few were strongly linked to immune age. We have now used this information to design a much more detailed experiment, aiming to understand more about what might be responsible for immune ageing. We want to understand in detail what happens in immune ageing. To do this, we plan to focus on people who have the same age, but very different immune ages. We want to understand not only what is different between them, but also how their immune systems respond differently to the same 'challenge'. To do this we will identify two groups of people with similar ages but very different immune ages and take blood samples before, during and after they receive their standard influenza and COVID booster vaccinations: we only need take blood samples while they have booster shots just as they would do in any case. From the blood samples we will purify a range of different immune cell types - both those we have linked to immune age and others likely to contribute. We can then analyse these immune cell populations in minute detail, measuring for each individual cell which genes are switched on, which proteins are present and the type of antibody or immune receptors they use. This is helpful as the level of detailed information generated allows us to identify the cells linked to 'older' immune responses, even those we may not have suspected were important (as we can measure all genes in every cell). We can also use this information to work out how cells are responding differently in the two groups of people. We can do this at each timepoint of the experiment (for example, before they get their vaccine) but we can also look at changes occurring over time, comparing before and after vaccination. After they receive their vaccine we will measure how effective a response they have made and also the extent to which they have produced an 'incorrect' response against their own body's proteins. By putting together all of this information we aim to identify changes in immune ageing that control the balance between helpful and harmful immunity. We believe this is the first step towards a better understanding of how medications should be used in the elderly to influence that balance: improving older peoples' ability to fight infection, cancer and to respond to vaccines and improving our ability to treat inflammatory disease also. This could have a huge impact on the duration and quality of life in ageing.",,2026,N/A,1660457.22,Human Populations,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Clinical,Unspecified,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity | Characterisation of vaccine-induced immunity,2023 +P30440,MR/X012883/1,A Celigo Whole Well Imaging Cytometer for the Crick Covid neutralisation pipeline,"The Crick achieves operational and research efficiencies and economies-of-scale through centralised facilities and functions, known as Science Technology Platforms, that provide all researchers at the Crick, irrespective of affiliation, with access to cutting-edge equipment for research and laboratory enabling functions such as the High Throughput Screening facility (HTS). The Crick Covid Surveillance unit (CCSU) is an offshoot of the HTS facility and was established to run a pipeline of activity delivering a high throughput live-virus antibody neutralisation assay to measure the ability of patient serum to prevent cell infection by SARS-CoV-2 across thousands of samples simultaneously. This unique neutralisation assay platform (developed in the HTS facility) is essential to many ongoing research studies, for example those assessing the likely impact of Variants of Concern on current vaccinated populations and in clinically vulnerable cohorts. The pipeline is able to generate neutralization data against new VOCs (e.g. Delta and Omicron) within 2-3 weeks upon receipt of a novel virus sample and can process thousands of samples per week at GCP level. Data from this pipeline has measured neutralising antibody titres against Delta and Omicron variants in participants in the Crick-Legacy study (recipients of both the Pfizer and Oxford-AstraZeneca vaccines). These data are shared with UK government scientific advisory boards, contributing to the extension of UK pandemic restrictions to allow more people to receive a second vaccine dose in summer 2021 and the successful booster campaign. Publications reporting these findings have been cited nearly 600 times. This pipeline also enabled the comparison of antibody titres in healthy adults with those of both cancer patients (Crick-CAPTURE study) and kidney dialysis patients (Crick-NAOMI study), providing important data on prioritisation of vulnerable patient groups. In addition, data on the in vitro neutralising efficacy of the synthetic monoclonal antibody, Sotrovimab was shared with NHSE and the Chief Medical Officer and supported the ongoing use of this drug for patients infected with Omicron BA.1 and BA.2. There are no other similar pipelines capable of this scale of live virus assay in the UK (possibly internationally) and with near real time reporting, the data produced remains a vital tool in the UK and international pandemic preparedness and response. Currently, the neutralisation pipeline is made robust by using multiple HTS liquid handling devices to ensure continuity of delivery. However, the primary imaging (and measurements derived from them) is restricted to one microscope, the Opera Phenix. This reliance on one imaging device is a weak point for this pipeline. This proposal is to deploy the Celigo scanning cytometer in this assay and thereby remove the dependence on one machine for a pipeline that needs to remain operational. Moreover, acquisition on the Celigo is 4-5 times faster meaning that pipeline throughput and capacity can be significantly increased. The Covid neutralisation pipeline accounted for 50% of HTS usage over 2020/21. Having a high-end microscope occupied with one type of assay necessarily restricts access by other users (currently measured in weeks of delay for access to the Opera Phenix). By moving the primary imaging platform for the CCSU activity to the Celigo, we would greatly increase the availability of high content microscopy to other Crick researchers and thereby improve service delivery for more than 100 Crick researchers who used the HTS facility over 20/21. The availability of a Celigo imager will also enable improvements to existing activities requiring analysis of cell populations (at scale) in the areas of radiation biology, stem cell biology and general cell viability. In addition, there will be new opportunities for users to explore automation of previously manual assays e.g. Influenza plaque assays",,2023,N/A,222336.86,Viruses,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Not applicable,,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations",2022 +P30444,MR/X009297/1,PITCH2 - Protective Immunity through T Cells in Healthcare workers 2,"COVID-19 has had a devastating impact on lives for many reasons, including illness, loss of life, restrictions to way of life and economic losses. We now see lower rates of severe disease and death despite continued infections from the virus (severe acute respiratory syndrome coronavirus 2: SARS-CoV-2), but we need to protect people with immune problems and be ready for future variants and related viruses. It is crucial that we understand how people's immune systems protect against both infection and severe disease, and how long immunity lasts. This information tells us whether we need to give booster vaccines again, who is at increased risk of infection and severe disease, how to fine tune the next generation of vaccines and can guide development of new drug treatments. Much research on the immune response to COVID-19 focusses on measuring antibodies in the blood, but there is a second vital arm to the body's learned response to infection: T cells. T cells are a group of white blood cells patrolling the bloodstream to defend against infection, and can be trained by vaccination and/or previous infection to recognise and destroy the virus causing COVID-19. T cells are likely to be particularly important at preventing severe disease, but are difficult to measure because fresh blood samples and specialised skills and equipment required. We have established a national group to track the T cell response to the SARS-CoV-2 virus in over time in over 2000 healthcare workers working in one of five cities (Birmingham, Liverpool, Newcastle, Oxford and Sheffield). This group, called the PITCH (Protective Immunity through T Cells in Healthcare workers) consortium, includes researchers from UK Health Security Agency who run the wider SIREN study which undertakes regular PCR screening and antibody testing from 44,546 healthcare workers in 135 NHS sites across the UK. PITCH allows study of the immune response in greater detail in our subgroup. So far our research findings have helped the UK government make decisions about when to give vaccines and who remains especially vulnerable. We demonstrated that people with previous infection make a much better antibody and T cell response after receiving vaccines, even after the third (booster) dose. We also showed that a longer dosing interval for the Pfizer vaccine gave higher antibody responses and lower but better memory quality T cell responses than a short dosing interval. Our latest work shows that after two doses of vaccine, the antibody response declines over six months, but the T cell response is well maintained, re-enforcing the idea that T cells are important for long term protection. T cells in vaccinated people still work well against the Omicron variant, which evades much of the body's neutralising antibody response. We have shared our T cell laboratory techniques with other researchers, and we work with national study teams such as OCTAVE to look at T cell responses in patients with immune issues compared to our healthier population of healthcare workers. We are now applying for funding to maintain the systems we have set up for the PITCH consortium. We need to follow-up our group of healthcare workers to see if the antibody and T cell response is wearing off in time, and to measure how people's immune response deal with any future variants of the virus. We also have an opportunity to learn more about the immune response to influenza (flu) because there has not been any flu in circulation since winter 2019/2020 due to the restrictions put in place for COVID-19. We will work together with the British Society for Immunology to explain our research to healthcare workers and the wider public, and listen to opinions on what the important questions are. We have assembled a highly productive group of researchers and will use PITCH2 as a springboard for long term deeper research studies to answer questions on the character and duration of immunity to SARS-CoV-2 virus and flu.",,2024,N/A,2456720.27,Human Populations,Unspecified,Adults (18 and older),Unspecified,Unspecified,Health Personnel,Clinical,Not applicable,Coronavirus | Orthomyxoviridae,Unspecified,,,,,,,,COVID-19 | Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics | Clinical characterisation and management | Vaccines research, development and implementation",Immunity | Disease pathogenesis | Characterisation of vaccine-induced immunity,2023 +P30490,2444474,Combining immunity and climate date streams to forecast infectious disease transmission,"Infectious disease transmission is driven by a complex interplay between population immunity, population behaviour and, in some instances, climate variation. Forecasting models aiming to predict future infectious disease transmission can be highly useful in public health planning and decision-making, and inform early warning and response systems. Forecasting model frameworks are increasingly incorporating multiple data streams to better capture the drivers of infectious disease transmission, and to improve the accuracy and reliability of forecasts. The aim of this PhD is to integrate serological and climate data within statistical and mathematical modelling frameworks to investigate the role of population immunity, climate and control interventions in driving infectious disease dynamics. As a case study, I will focus on two pressing health threats in the Dominican Republic: SARS-CoV-2 and dengue virus. In my first two chapters, I will quantify the risk of SARS-CoV-2 reinfection using longitudinal serological data from the United States. This will then inform the parameterisation of a compartmental model to investigate the drivers of SARS-CoV-2 transmission in the Dominican Republic and simulate possible future epidemic scenarios as vaccination coverage increases. In my third chapter, I will quantify the effect of climate variation on dengue risk in the Dominican Republic using a spatiotemporal Bayesian modelling framework and evaluate the viability of a climate-driven dengue early warning system. Finally, I will develop a transmission dynamic model integrating surveillance data, serological data, and climate data to investigate the drivers of dengue transmission in the Dominican Republic. I will develop and evaluate forecasts for early warning of dengue outbreaks and compare the success of these forecasts with the statistical climate-based approach in the previous chapter. Overall, I aim to integrate novel data streams within modelling frameworks to improve infectious disease forecasting, in an approach that may be generalisable to other Caribbean islands and Small Island Developing States. This research will be developed in close collaboration with the Dirección General de Epidemiologia (DIGEPI) in the Dominican Republic in order to ensure that project outputs align with the public health needs in the Dominican Republic, as well as the needs of key partners such as the US CDC and PAHO/WHO. During this project I am furthering my quantitative analysis skills, in particular my knowledge of mechanistic and statistical modelling, as well as Bayesian inference techniques. Additionally, I am looking forward to enhancing my interdisciplinary skills by integrating insights from climate-driven modelling approaches with mechanistic transmission dynamic modelling methods to improve forecasting of infectious diseases.",,2024,N/A,,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Flaviviridae,,,,,,,,,COVID-19 | Other,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Epidemiological studies,Disease transmission dynamics,2020 +P30495,2736919,Comparing the Airborne Survival of Enveloped and Non-enveloped Viruses,"CDT student- will be updated when project proposal is written (summer 2023) but outline description is: Respiratory aerosol particles transmit pathogens such as SARS-CoV-2 between infected and susceptible individuals. While airborne, the infectivity of viruses declines at a rate that is influenced by the microphysical processes occurring in the aerosol (e.g. water evaporation). This project will compare the airborne survival of enveloped and non-enveloped viruses. Theme: Aerosols and Health",,2026,N/A,,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Pathogen: natural history, transmission and diagnostics","Pathogen morphology, shedding & natural history",2022 +P30891,10075383,Future Materials for the control of airborne disease transmission with the next generation of face masks,"Paravir has developed an **antiviral**, **disposable material** technology for facemasks and other medical nonwovens. Our technology is **recyclable, safe for humans, animals, marine and plant life.** It is also **incredibly cheap to make** meaning antiviral masks can become a standard intervention for variants of Covid 19 (SARS CoV19) and Bird Flu (H5N1). We are seeking grant funding for the construction of a pilot line machine to evaluate the manufacturability of our antimicrobial application. This innovation adds function to off-the-shelf nonwovens which interfere and denature virus, bacteria, fungi and parasites reducing the user's exposure to infectious diseases. Our technology has recently been granted a UK Patent. Product testing has passed ISO 18184 (Antiviral) and ISO 20743 (Antibacterial) Materials.",,2023,N/A,62167.82,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Orthomyxoviridae | Novel Pathogen,H5,,,,H5N1,,,,COVID-19 | Pandemic-prone influenza | Disease X,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,Infection prevention and control,"Barriers, PPE, environmental, animal and vector control measures",2023 +P32022,2401512,A Critical Analysis of Pupil Behaviour,"This research project will focus on alternatives to school exclusion in England. Since 2012/ 13 exclusions from schools in England had been steadily increasing, peaking at 7,894 permanent exclusions and 438,265 fixed term exclusions in the 2018/ 19 academic year. However, the most recent data taken from the 2019/ 20 academic year shows instances of permanent exclusions and fixed term exclusions have both decreased, with the figures standing at 5,057 and 310,733 respectively (DfE, 2021) - it is important to note that this data was significantly impacted by the COVID-19 pandemic and subsequent closure of schools. The pandemic brought to the fore concerns regarding the 'lost learning' of children unable to attend school (Ofsted, 2020; Adams, 2021; EEF, 2021) yet the lost learning of excluded pupils has never received such attention in the media and public discourse. The extent to which exclusion is used as a behaviour management tool in the English education system provides the fundamental basis of the rationale for this research - but it goes further than this. Official Department for Education statistics show that certain groups of pupils are more likely to experience exclusion from school namely; Black Caribbean pupils, Gypsy, Roma and Traveller pupils, boys, pupils eligible for Free School Meals (FSM), and pupils with Special Educational Needs (SEN) especially where there is no education health and care plan (EHCP) (DfE, 2021). Furthermore, alternative provision is often considered to be a positive change for excluded pupils, perhaps even a solution to the problem, such views were clearly articulated in the Timpson review of school exclusion (Timpson, 2019). Conversely, it is well known that of pupils enrolled in alternative provision fewer than 2% achieve what is considered to be a good pass in maths and English (Hutchinson, 2020). As such, the desire to expand provision that is ineffective and disproportionately accommodates the groups of pupils mentioned above could be seen as an attempt to 'market the marginalised' (Perera, 2020). This research will take a fixed sequential exploratory approach to research design, involving semi-structured interviews with educational professionals working in alternative education settings and a survey of young people who have experienced exclusion from mainstream education in England.",,2024,N/A,,Human Populations,Unspecified,Adolescent (13 years to 17 years) | Adults (18 and older) | Children (1 year to 12 years),Unspecified,Unspecified,Other,Non-Clinical,,Coronavirus,,,,,,,,,COVID-19,UK Research and Innovation (UKRI),United Kingdom,Europe,,,,,,,,"Secondary impacts of disease, response & control measures",Social impacts,2020 +P32202,10090901,Demonstrating the potential for portable detection of bird flu.,"Project aim is to provide capability for early in-field direct testing of unprocessed biological samples e.g. swabs and blood for economically important veterinary pathogens, in this case screening swab samples taken from the beaks and cloaca of birds for detecting ""bird flu"". Initially we aim to support existing lab testing and ultimately explore the potential for moving tests into the field or farm. BG Research have developed a novel method and instrument for performing sensitive in-field molecular diagnostic tests for the detection of viruses without the requirement for expert scientists or shipping of samples to a test-lab and utilising the gold-standard PCR test methodology. Tests could be performed at ports of entry to prevent diseases being imported, on farms or at slaughterhouses to support surveillance/quarantine and emergency response. By performing rapid, sensitive, and cost-effective tests wherever required, the BGR technology could help protect the UK by preventing potential importation of infectious diseases at entry points and expedite outbreak response where incursions require rapid disease response activities. For example, the outbreaks of FMD in the UK cost the economy £10bn and COVID-19 is thought to have originated from wildlife. Such technology could assist Defra to more effectively monitor transboundary veterinary diseases and provide real-time data to contribute to the control of these diseases, reducing the socio-economic impacts of future outbreaks. We will develop the platform from a lab-based technology demonstrator into a late-stage prototype capable of being operated off-grid and moving the technology closer to the intended portable testing market. Test development assessment will be undertaken at the Animal and Plant Health Agency (APHA) where the necessary scientific expertise and facilities required to work with these pathogens are available. Bird flu has been in the news continually for the past few years and over 8.5 million UK birds have been lost/culled in that period, the impact of this has been seen by the consumer by the lack of eggs in the supermarket and turkeys for Christmas. A novel tool such as this could assist in future outbreak management -- reducing the economic burden and reducing the risk of bird flu becoming a human pathogen. The platform and associated validated tests would be made in the UK and marketed globally by BG, supporting growth and employment in UK Life Sciences and supply chains, while ensuring the UK is better prepared to respond to future epidemics of important human and animal pathogens.",,2025,N/A,263371.87,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Orthomyxoviridae,Other,,,,,,,,Pandemic-prone influenza,UK Research and Innovation (UKRI),United Kingdom,Europe,,,Innovation,,,,,"Pathogen: natural history, transmission and diagnostics",Diagnostics,2024 +P32708,N/A,Disease X,"Promising technology to be tested in preclinical studies funded by CEPI The innovation could enable up to 100 times less antigen-encoded mRNA per vaccine dose and for parts of the vaccine to be made ahead of an outbreak Some lifesaving COVID-19 vaccines use mRNA, and the innovation could be key to more rapidly responding to future threats 07 March 2024, OSLO, Norway and BOSTON, MA - Scientists in the US are set to test a new vaccine approach that could overcome some of the challenges associated with the latest mRNA vaccine designs and more rapidly create pandemic-busting vaccines in as little as 100 days. With up to US $1 million in funding from CEPI, researchers at Amplitude Therapeutics will perform preclinical studies that assess whether their trans-amplifying mRNA vaccine approach could provide a simplified alternative to the self-amplifying mRNA vaccine technique being used today. Alongside conventional* mRNA vaccines-the technology behind multiple safe and effective COVID-19 vaccines that have helped to save millions of lives-self-amplifying mRNA designs have become more prominent in recent years, with the first-ever licensure of a self-amplifying mRNA COVID-19 vaccine in Japan in November 2023. Rather than the traditional vaccine approach of injecting an antigen (a substance that induces an immune response) directly into the recipient, mRNA platforms use the body's own cell machinery to make the antigen. Self-amplifying mRNA vaccines are even more specialised as they contain genetic instructions that not only encode for the antigen but also replicase, an enzyme that serves as a built-in photocopier teaching the body how to make more mRNA. While this self-copying design offers important advantages over conventional mRNA vaccines, such as the potential to reduce the dose of mRNA needed while maintaining the effectiveness of the vaccine, there are limitations. For example, the additional genetic instructions required for the replicase make the vaccine sequence at least three times longer than standard mRNA vaccine sequences which can lead to difficulties during manufacturing and delivery. Trans-amplifying mRNA vaccines, which consist of two separate, shorter RNA fragments-one encoding the antigen and one encoding the replicase-may provide an important solution. By separating out the target antigen and replicase sequences, the vaccine could be more easily produced in vaccine manufacturing facilities. Compared to conventional mRNA vaccines, the design could also mean up to 100 times less antigen-encoded RNA is needed per dose and the replicase enzyme can be produced ahead of an outbreak as it does not need to be combined with the target antigen sequence. Dr In-Kyu Yoon, Acting Executive Director of Vaccine R&D, CEPI, said: ""Many exciting technologies are coming out of the COVID-19 pandemic, and we must investigate whether they fit the bill of developing vaccines against future viral threats within a 100-day timeline. We already know mRNA is fast and flexible, and now new techniques like trans-amplifying mRNA vaccine technologies may further enhance its offering by significantly extending antigen supply while also allowing for key components of the vaccine to be made ahead of time."" Dr Cory Sago, CEO of Amplitude Therapeutics, said: ""We are grateful for CEPI's support as we work to advance trans-amplifying RNA vaccines for pandemic preparedness. Our data suggests that trans-amplifying RNA may have some distinct advantages over existing mRNA technologies, including improved expression and flexibility of manufacturing."" This is the first partnership to be announced as part of CEPI's call for vaccine R&D and manufacturing innovations which could be critical to helping the world better prepare for future epidemics and pandemics in support of the 100 Days Mission. The ambitious goal, embraced by the G7 and G20, seeks to develop vaccines, diagnostics and therapeutics against novel pathogens within 100 days of virus identification and give the world a chance of preventing the next pandemic. CEPI and Amplitude Therapeutics are committed to enabling equitable access to the outputs of their partnership, in line with CEPI's Equitable Access Policy. This ultimately includes commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding. Project results, including data generated as part of this project, will be published open access for the benefit of the global scientific community. ENDS Notes to Editors CEPI is supporting preclinical work to establish the Amplitude Therapeutics platform using Influenza as the model target pathogen. Further details on CEPI's Call for Innovations to Prepare for Future Epidemics and Pandemics Call for Proposals are available here. Applications are open for two Focus Areas: 1) advancing innovative rapid-response vaccine platforms that can transform the response to a future Disease X and 2) developing new vaccine candidates against CEPI priority pathogens with epidemic or pandemic potential and viral families. Additional awardees supported by CEPI's innovations call are expected to be announced in the coming months, following accelerated expert review of submitted proposals. About CEPI CEPI was launched in 2017 as an innovative partnership between public, private, philanthropic and civil organisations. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of more than 50 vaccine candidates or platform technologies against multiple known high-risk pathogens or a future Disease X. Central to CEPI's pandemic-beating five-year plan for 2022-2026 is the '100 Days Mission' to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days. About Amplitude Therapeutics Amplitude Therapeutics, founded in 2022, is a biotechnology company developing a next-generation trans-amplifying RNA platform that has advantages over existing RNA technologies including increased in vivo expression and improved manufacturing. Amplitude is applying the trans-amplifying RNA platform to create differentiated vaccines and therapeutics across protein replacement, immunology and genetic medicines.",,-99,Amplitude Therapeutics,1000000,Other,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Novel Pathogen,Unspecified,,,,,,,,Disease X,Coalition for Epidemic Preparedness Innovations (CEPI),International,International,Unspecified,Unspecified,Innovation,,,,,"Vaccines research, development and implementation",Pre-clinical studies | Vaccine design and administration,2024 +P32717,101195465,Tackling and investigating the South-Kivu mpox outbreak (MBOTE-SK),"With the Mpox Biology, Outcome, Transmission, and Epidemiology in South Kivu (MBOTE-SK) project, we seek emergency funding to address one of the most alarming mpox outbreaks currently unfolding: the ongoing emergence of a new lineage of monkeypox virus (MPXV, clade Ib) in South Kivu, Democratic Republic of the Congo (DRC). This outbreak is particularly concerning due to its extensive human-to-human transmission through sexual contact in a densely populated region characterized by a large sex industry and significant cross-border movement. Without swift intervention, there is a high risk of the outbreak spreading internationally, penetrating sexual networks worldwide. In this project, we will leverage our extensive experience with mpox outbreaks in the DRC and our current presence in South Kivu to tackle this outbreak through a combined approach of research and response. To achieve this, we will build on local and national expertise and strengthen the DRC's research institutions, and align with the international response. This project has four foundational pillars, each designed to simultaneously strengthen the response and comprehensively describe clade Ib MPXV, including its clinical presentation, mode of transmission, at-risk populations, and virological evolution. Pillar 1 strengthens active case finding and epidemiological surveillance to map and monitor the spread of clade Ib MPXV. Pillar 2 supports real-time genomic surveillance to track the genetic evolution of the strain. Pillar 3 enhances clinical care through an in-depth clinical characterization study. Pillar 4 engages key populations (including sex workers) to study community spread, vaccine hesitancy and stigma. These four pillars eventually feed into Pillar 5, by informing on how to best target the Ministry of Health's planned vaccination campaign (with the Modified Vaccinia Ankara vaccine) and documenting its impact and real-world effectiveness (using the established platforms of Pillars 1-4).",2024,2027,INSTITUUT VOOR TROPISCHE GENEESKUNDE,2255759.24,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Sex workers,Unspecified,Clinical | Non-Clinical,Not applicable,Poxviridae,,,,,,,,,Mpox,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa | Americas | Europe,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation | Policies for public health, disease control & community resilience","Research for enhanced understanding of the disease | Viral evolution in different contexts & implications | Disease epidemiology & risk factors & modes of transmission | Ongoing assessment & evaluation of surveillance | Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course | Immunisation strategies to optimise use of available vaccines | Behavioural drivers of risk and protection in different contexts",Belgium,France | Congo (DRC) | France | Canada | Congo (DRC),"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Vaccines research, development and implementation | Policies for public health, disease control & community resilience","Pathogen genomics, mutations and adaptations | Disease surveillance & mapping | Supportive care, processes of care and management | Vaccine design and administration | Characterisation of vaccine-induced immunity | Approaches to public health interventions | Community engagement | Vaccine/Therapeutic/ treatment hesitancy | Policy research and interventions",2024 +P32718,101195186,Implementing wastewater and environmental surveillance for Mpox in Sub-Saharan Africa (ODIN-MPox),"Mpox, a re-emerging viral zoonotic disease, has recently posed significant public health challenges in sub-Saharan Africa, particularly in the Democratic Republic of Congo (DRC). The disease has led to thousands of suspected cases and hundreds of deaths, prompting the DRC Ministry of Health to declare a Public Health Emergency in April 2024. Given the rapid spread and high fatality rate of the outbreak, a coordinated research response is urgently needed to understand and mitigate this public health threat. Mpox's emergence as a significant public health threat in sub-Saharan Africa aligns with Project ODIN's core objective of addressing critical infectious pathogens through genomic surveillance and wastewater-based epidemiology. Building upon the successful foundation of Project ODIN, this proposal aims to implement a comprehensive water genomic surveillance system specifically targeting the Mpox outbreak in the DRC and neighboring countries. By leveraging advanced genomic surveillance and wastewater-based epidemiology, this initiative will provide novel, critical, and timely insights into the presence and spread of the Mpox virus in the environment. This information will guide targeted public health interventions, such as targeted vaccination campaigns and resource allocation to high-risk areas. Additionally, the approach will enable the early detection of the Mpox virus in water sources, allowing for rapid public health interventions to prevent further transmission. The project will identify Mpox virus sublineages with the highest impact on case numbers and fit them into a global context, providing evidence of international sublineages that likely emerged or spread early in the DRC and neighboring countries. This data will be crucial not only in addressing the immediate outbreak but also in contributing to building global public health strategies and preparedness for future outbreaks by gaining a deeper understanding of the Mpox virus itself.",2024,2026,LUNDS UNIVERSITET,1504660.09,Viruses | Environment | Other,Not applicable,Not Applicable,Unspecified,Not applicable,,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa | Europe,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies",Viral evolution in different contexts & implications | Ongoing assessment & evaluation of surveillance,Sweden,Burkina Faso | Finland | Tanzania | Norway | United Kingdom | Congo (DRC) | Belgium | Belgium,"Pathogen: natural history, transmission and diagnostics | Animal and environmental research and research on diseases vectors | Epidemiological studies","Diagnostics | Pathogen genomics, mutations and adaptations | Disease surveillance & mapping",2024 +P32719,101195465,Impact of MPXV infection on pregnancy outcome and newborn health (PREGMPOX),"Pregnant women have an increased risk of severe mpox disease, however, the underlying mechanisms remain elusive. To better understand altered transmission pattern of MPXV and its impact on this vulnerable population, PREGMPOX aims to assess the extent of MPXV spreading among pregnant women in South Kivu and neighboring regions through both passive and active surveillance. Passive surveillance will utilize existing health data from local facilities, capturing reported cases, while active surveillance will involve direct community engagement to identify and document unreported cases. In sentinel study sites in hot spot areas, the prevalence of MPXV infection among pregnant women will be investigated and potential transmission routes determined. Moreover, our project aims to document and analyze adverse pregnancy outcomes associated with MPXV infection, such as spontaneous losses, stillbirths, preterm deliveries, and neonatal infection. MPXV+ pregnant women will be asked to participate in a cohort study where they will be followed until delivery to document pregnancy outcomes, maternal immune response, and virus abundance and pathological changes in the placenta. This will help to determine specific risk factors and modes and frequencies of vertical transmission to the unborn, and generate a list of clinical and immunological predictors for adverse outcomes for pregnant women and neonates. As a prerequisite to evaluate the safety of the MVA-BN vaccine and tecovirimat treatment in pregnant women, we will create a comprehensive register of adverse pregnancy outcomes, using a pharmacovigilance model to monitor and analyze adverse events following immunization and treatment. The results of our multidisciplinary studies will be crucial for developing guidelines and recommendations to manage mpox more effectively during pregnancy, and for potentially influencing global health policies.",2024,2027,UNIVERSITEIT ANTWERPEN,1364625,Human Populations,Unspecified,Adults (18 and older) | Newborns (birth to 1 month),Unspecified,Pregnant women,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Europe,Africa | Europe,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation | Secondary impacts of disease, response & control measures","Research for enhanced understanding of the disease | Disease epidemiology & risk factors & modes of transmission | Transmission dynamics including risk & determinants of acquisition | Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course | Treatment approaches in advanced HIV disease or other immunocompromising conditions. | Development of equitable, accessible, safe & effective therapeutics | Development of equitable, accessible, safe and effective vaccines | Prevention of complications & social sequelae",Belgium,Uganda | Germany | Congo (DRC),"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management | Therapeutics research, development and implementation | Vaccines research, development and implementation","Pathogen morphology, shedding & natural history | Immunity | Disease transmission dynamics | Disease susceptibility | Disease pathogenesis | Supportive care, processes of care and management | Post acute and long term health consequences | Adverse events associated with therapeutic administration | Adverse events associated with immunization",2024 +P32720,101194676,Deciphering host genetics and viral determinants of MPOX epidemiology in the Democratic Republic of Congo (DECIPHER-MPOX),"Background: Monkeypox virus (MPV) is a member of the Poxviridae family that includes smallpox, cowpox and chickenpox viruses. Endemic to equatorial Africa following casual human to animal or human to human transmission , recent events have seen an increased incidence with indications of sexual transmission. The disease is characterized by fever, muscle aches, skin rash, lymphadenopathy, oral sores, sore throat, cough, etc. Within any cluster of high risk contacts of a case mpox; however, not everyone exposed develops clinical disease. Moreover, among those contacts who develop mpox, not everyone gets severe disease or dies. Hypothesis: Host genetic & viral factors explain the differential outcomes following exposure to MPV. Objectives: To determine the host genetic and viral determinants of mpox disease in Kamituga area, South Kivu province, DRC. Specifically, we will (I) establish well phenotyped cohorts of house-hold contacts, (II) determine rare variants via family trios; (III) undertake RNASeq for transcriptomics, and (IV) study differential cellular immunity profiles using digital cell sorting (DCS) , (V) identify viral variants that drive severe disease Methods: Whole exome sequencing (WES), transcriptomics and DCS studies of house-family contacts clinically prequalified by PCR and serological testing. Virus gDNA will be reverse transcribed from sequenced host RNA and characterized by comparative genomics and phylogeny. Potential impact: This project will elucidate host genetic & viral determinants of susceptibility to mpox disease in context of natural exposure and infection; that may serve as correlates of immune protection following vaccination.",2024,2026,National Health Laboratory Services,1375542,Human Populations | Viruses,Unspecified,Unspecified,Unspecified,Unspecified,Unspecified,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,European & Developing Countries Clinical Trials Partnership (EDCTP),Europe,Europe,Africa,Africa | Americas | Europe,,"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Research for enhanced understanding of the disease | Disease epidemiology & risk factors & modes of transmission | Promote improved understanding of the disease (including evidence synthesis) | Spectrum & determinants of mpox clinical presentation, pathogenesis & disease course",South Africa,Congo (DRC) | Uganda | Canada | United Kingdom | Uganda | Congo (DRC),"Pathogen: natural history, transmission and diagnostics | Epidemiological studies | Clinical characterisation and management","Pathogen morphology, shedding & natural history | Pathogen genomics, mutations and adaptations | Immunity | Disease susceptibility | Prognostic factors for disease severity | Disease pathogenesis",2024 +P32721,1776000407,Development of multi-valent COVID-19 and mpox mRNA vaccine candidates,N/A,-99,2025,National Institute of Health (Korea),167669.17,Unspecified,Not applicable,Not Applicable,Unspecified,Not applicable,Not applicable,Non-Clinical,,Coronavirus | Poxviridae,,,,,,,,,COVID-19 | Mpox,,South Korea,Western Pacific,Western Pacific,Western Pacific,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",South Korea,South Korea,"Vaccines research, development and implementation",Pre-clinical studies,2023 +P32722,1776000394,Evaluation of protective effect of smallpox vaccines against monkeypox virus in monkey model,N/A,-99,2024,HK inno.N Corporation,1492436.09,Animals,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,,South Korea,Western Pacific,Western Pacific,Western Pacific,,"Vaccines research, development and implementation","Development of equitable, accessible, safe and effective vaccines",South Korea,South Korea,"Vaccines research, development and implementation",,2023 +P32723,1776000244,Evaluation of cross-immunogenicity between smallpox vaccine strain and monkeypox virus,N/A,-99,2023,National Institute of Health (Korea),230769.23,Viruses,Not applicable,Not Applicable,Not applicable,Not applicable,Not applicable,Non-Clinical,,Poxviridae,,,,,,,,,Mpox,,South Korea,Western Pacific,Western Pacific,Western Pacific,,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Research for enhanced understanding of the disease | Immunisation strategies to optimise use of available vaccines,South Korea,South Korea,"Pathogen: natural history, transmission and diagnostics | Vaccines research, development and implementation",Immunity,2022 \ No newline at end of file